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Embryonic factors are essential for endometrial decidualization during early pregnancy. Yang et al. report that primary trophoblast giant cells, the embryonic cells directly contacting the endometrium, can secrete type I interferon IFNK and lipoprotein lipase to strengthen the decidual interferon response and lipid accumulation, respectively, thus ensuring early pregnancy.
in Cell Reports: Current Issue on 2024-05-18 00:00:00 UTC.
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In animal tissues, several cell types migrate along blood vessels, raising the possibility that blood flow influences cell migration. Here, we show that blood flow promotes the migration of new olfactory-bulb neurons in the adult brain. Neuronal migration is facilitated by blood flow, leading to accumulation of new neurons near blood vessels with abundant blood flow. Blood flow inhibition attenuates blood vessel-guided neuronal migration, suggesting that blood contains factors beneficial to neuronal migration. We found that ghrelin, which is increased in blood by hunger, directly influences neuronal migration. Ghrelin signaling promotes somal translocation by activating actin cytoskeleton contraction at the rear of the cell soma. New neurons mature in the olfactory bulb and contribute to the olfactory function for sensing odorants from food. Finally, we show that neuronal migration is increased by calorie restriction, and that ghrelin signaling is involved in the process. This study suggests that blood flow promotes neuronal migration through blood-derived ghrelin signaling in the adult brain, which could be one of the mechanisms that improve the olfactory function for food-seeking behavior during starvation.
in bioRxiv: Neuroscience on 2024-05-18 00:00:00 UTC.
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Brain Sciences, Vol. 14, Pages 513: mTBI Biological Biomarkers as Predictors of Postconcussion Syndrome—Review
Brain Sciences doi: 10.3390/brainsci14050513
Authors:
Ewelina Stępniewska
Maria Kałas
Justyna Świderska
Mariusz Siemiński
Postconcussion syndrome (PCS) is one of the leading complications that may appear in patients after mild head trauma. Every day, thousands of people, regardless of age, gender, and race, are diagnosed in emergency departments due to head injuries. Traumatic Brain Injury (TBI) is a significant public health problem, impacting an estimated 1.5 million people in the United States and up to 69 million people worldwide each year, with 80% of these cases being mild. An analysis of the available research and a systematic review were conducted to search for a solution to predicting the occurrence of postconcussion syndrome. Particular biomarkers that can be examined upon admission to the emergency department after head injury were found as possible predictive factors of PCS development. Setting one unequivocal definition of PCS is still a challenge that causes inconsistent results. Neuron Specific Enolase (NSE), Glial Fibrillary Acidic Protein (GFAP), Ubiquitin C-terminal Hydrolase-L1 (UCH-L1), Serum Protein 100 B (s100B), and tau protein are found to be the best predictors of PCS development. The presence of all mentioned biomarkers is confirmed in severe TBI. All mentioned biomarkers are used as predictors of PCS. A combined examination of NSE, GFAP, UCH-1, S100B, and tau protein should be performed to detect mTBI and predict the development of PCS.
in Brain Sciences on 2024-05-18 00:00:00 UTC.
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Brain Sciences, Vol. 14, Pages 512: Parafoveal Processing of Orthography, Phonology, and Semantics during Chinese Reading: Effects of Foveal Load
Brain Sciences doi: 10.3390/brainsci14050512
Authors:
Lei Zhang
Liangyue Kang
Wanying Chen
Fang Xie
Kayleigh L. Warrington
The foveal load hypothesis assumes that the ease (or difficulty) of processing the currently fixated word in a sentence can influence processing of the upcoming word(s), such that parafoveal preview is reduced when foveal load is high. Recent investigations using pseudo-character previews reported an absence of foveal load effects in Chinese reading. Substantial Chinese studies to date provide some evidence to show that parafoveal words may be processed orthographically, phonologically, or semantically. However, it has not yet been established whether parafoveal processing is equivalent in terms of the type of parafoveal information extracted (orthographic, phonological, semantic) under different foveal load conditions. Accordingly, the present study investigated this issue with two experiments. Participants’ eye movements were recorded as they read sentences in which foveal load was manipulated by placing a low- or high-frequency word N preceding a critical word. The preview validity of the upcoming word N + 1 was manipulated in Experiment 1, and word N + 2 in Experiment 2. The parafoveal preview was either identical to word N + 1(or word N + 2); orthographically related; phonologically related; semantically related; or an unrelated pseudo-character. The results showed robust main effects of frequency and preview type on both N + 1 and N + 2. Crucially, however, interactions between foveal load and preview type were absent, indicating that foveal load does not modulate the types of parafoveal information processed during Chinese reading.
in Brain Sciences on 2024-05-18 00:00:00 UTC.
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Brain Sciences, Vol. 14, Pages 511: Mapping the Neural Basis of Neuroeconomics with Functional Magnetic Resonance Imaging: A Narrative Literature Review
Brain Sciences doi: 10.3390/brainsci14050511
Authors:
Carlo A. Mallio
Andrea Buoso
Massimo Stiffi
Laura Cea
Daniele Vertulli
Caterina Bernetti
Gianfranco Di Gennaro
Martijn P. van den Heuvel
Bruno Beomonte Zobel
Neuroeconomics merges neuroscience, economics, and psychology to investigate the neural basis of decision making. Decision making involves assessing outcomes with subjective value, shaped by emotions and experiences, which are crucial in economic decisions. Functional MRI (fMRI) reveals key areas of the brain, including the ventro-medial prefrontal cortex, that are involved in subjective value representation. Collaborative interdisciplinary efforts are essential for advancing the field of neuroeconomics, with implications for clinical interventions and policy design. This review explores subjective value in neuroeconomics, highlighting brain regions identified through fMRI studies.
in Brain Sciences on 2024-05-18 00:00:00 UTC.
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The mechanisms by which brain insults lead to subsequent epilepsy remain unclear. Insults including trauma, stroke, infections, and long seizures (status epilepticus, SE) increase the nuclear expression and chromatin binding of the neuron-restrictive silencing factor/RE-1 silencing transcription factor (NRSF/REST). REST/NRSF orchestrates major disruption of the expression of key neuronal genes, including ion channels and neurotransmitter receptors, potentially contributing to epileptogenesis. Accordingly, transient interference with REST/NRSF chromatin binding after an epilepsy-provoking SE suppressed spontaneous seizures for the 12 d duration of a prior study. However, whether the onset of epileptogenesis was suppressed or only delayed has remained unresolved. The current experiments determined if transient interference with REST/NRSF chromatin binding prevented epileptogenesis enduringly or, alternatively, slowed epilepsy onset. Epileptogenesis was elicited in adult male rats via systemic kainic acid-induced SE (KA-SE). We then determined if decoy, NRSF-binding–motif oligodeoxynucleotides (NRSE-ODNs), given twice following KA-SE (1) prevented REST/NRSF binding to chromatin, using chromatin immunoprecipitation, or (2) prevented the onset of spontaneous seizures, measured with chronic digital video-electroencephalogram. Blocking NRSF function transiently after KA-SE significantly lengthened the latent period to a first spontaneous seizure. Whereas this intervention did not influence the duration and severity of spontaneous seizures, total seizure number and seizure burden were lower in the NRSE-ODN compared with scrambled-ODN cohorts. Transient interference with REST/NRSF function after KA-SE delays and moderately attenuates insult-related hippocampal epilepsy, but does not abolish it. Thus, the anticonvulsant and antiepileptogenic actions of NRSF are but one of the multifactorial mechanisms generating epilepsy in the adult brain.
in eNeuro on 2024-05-17 16:30:25 UTC.
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Mismatch negativity (MMN) is commonly recognized as a neural signal of prediction error evoked by deviants from the expected patterns of sensory input. Studies show that MMN diminishes when sequence patterns become more predictable over a longer timescale. This implies that MMN is composed of multiple subcomponents, each responding to different levels of temporal regularities. To probe the hypothesized subcomponents in MMN, we record human electroencephalography during an auditory local–global oddball paradigm where the tone-to-tone transition probability (local regularity) and the overall sequence probability (global regularity) are manipulated to control temporal predictabilities at two hierarchical levels. We find that the size of MMN is correlated with both probabilities and the spatiotemporal structure of MMN can be decomposed into two distinct subcomponents. Both subcomponents appear as negative waveforms, with one peaking early in the central-frontal area and the other late in a more frontal area. With a quantitative predictive coding model, we map the early and late subcomponents to the prediction errors that are tied to local and global regularities, respectively. Our study highlights the hierarchical complexity of MMN and offers an experimental and analytical platform for developing a multitiered neural marker applicable in clinical settings.
in eNeuro on 2024-05-17 16:30:25 UTC.
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Current theories of decision-making propose that decisions arise through competition between choice options. Computational models of the decision process estimate how quickly information about choice options is integrated and how much information is needed to trigger a choice. Experiments using this approach typically report data from well-trained participants. As such, we do not know how the decision process evolves as a decision-making task is learned for the first time. To address this gap, we used a behavioral design separating learning the value of choice options from learning to make choices. We trained male rats to respond to single visual stimuli with different reward values. Then, we trained them to make choices between pairs of stimuli. Initially, the rats responded more slowly when presented with choices. However, as they gained experience in making choices, this slowing reduced. Response slowing on choice trials persisted throughout the testing period. We found that it was specifically associated with increased exponential variability when the rats chose the higher value stimulus. Additionally, our analysis using drift diffusion modeling revealed that the rats required less information to make choices over time. These reductions in the decision threshold occurred after just a single session of choice learning. These findings provide new insights into the learning process of decision-making tasks. They suggest that the value of choice options and the ability to make choices are learned separately and that experience plays a crucial role in improving decision-making performance.
in eNeuro on 2024-05-17 16:30:25 UTC.
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Scientists and medical experts are beginning to understand the significant role that a woman’s past reproductive experiences play in her potential risk of developing heart disease. Reproductive history is seldom considered when assessing the cardiovascular risk. Infertility, high blood pressure, and hypertension are risk factors for heart disease. Additional analyses were conducted to determine whether the apparent increase in risk could be influenced by other risk factors associated with infertility such as irregular menstruation, thyroid conditions, and waist circumference. This study aimed to investigate the association between cardiovascular risk and infertility in women and those who are fertile. The objectives of this study were to estimate the levels of serum creatinine kinase (MB) in both infertile and fertile control groups, as well as to estimate the LDL and HDL levels in the same groups. The study group comprised 78 participants, of which 39 were fertile and 39 were infertile. CK (MB), HDL, LDL, Uric acid, and high sensitivity C reactive Protein (hs-CRP) levels were analyzed. In this study, we discuss how infertility may share common pathways with cardiovascular diseases. Numerous mechanisms may be involved in mediating infertility, including ovulatory abnormalities, endometriosis, and uterine fibroids. For example, in addition to having lower HDL levels, women with polycystic ovary syndrome (PCOS) are more likely to have higher levels of total cholesterol, triglycerides, and LDL. PCOS patients typically exhibit elevated UA levels and hyperuricemia, which are commonly associated with increased androgen levels.
in F1000Research on 2024-05-17 16:13:27 UTC.
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Meningiomas are one of the most commonly occurring, extra-axial, primary tumors of central nervous system that are slow-growing in nature with a female predominance mostly occurring in the mid-late twenties. The clinical symptoms of atypical meningioma include headache, seizures, change in personality or behavior, development of a localized neurologic impairment, drowsiness, confusion, loss of hearing or tinnitus, fatigue on exertion, projectile vomiting and visual disturbances. If a meningioma is left untreated, it can cause problems such as loss of neurological function, weakness/numbness, hearing or vision loss, and balance problems. Sometimes there are worsening signs of persistent headaches, origin of new episodes of seizures, or increased intracranial pressure and neurological evaluation should be performed, followed by radiological studies if necessary. The best investigations for early diagnosis are CT and Magnetic Resonance Imaging scans (MRI). Total surgical excision of the tumor is the best management option for the neurological symptoms. In certain situations, such as atypical, malignant, or recurrent meningioma, radiation with a cumulative dose of 45-60 Gy is now employed There is a long-term re-occurrence rate of completely and incompletely resected atypical meningioma. Radiotherapy is beneficial in patients with low surgical risk, meningiomas in surgically inaccessible areas, and advanced age. Hormonal therapy and chemotherapy can be attempted when meningiomas are unresectable. In recurrent meningiomas, chemotherapy with hydroxyurea appears to be fairly active and has been mildly beneficial, as has hormonal therapy with progesterone antagonists. Thus, early diagnosis and management are essential to reduce neurological compromise and imprdaove the survival rate of patients with brain tumors.
in F1000Research on 2024-05-17 15:59:50 UTC.
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Background Nasopharyngeal swab RT-PCR is the standard procedure for COVID-19 testing. In patients with tracheostomy with an altered airway that bypasses the nasopharynx, the yield of samples from different sites is unknown. This information will be essential for formulating a sample collection method for COVID-19 RT-PCR testing in patients undergoing tracheostomy. Methods This was a cross-sectional study. Nasopharyngeal swabs and tracheal secretion (via closed-circuit secretion suction) samples were collected from 100 patients with a non-plugging tracheostomy tube at Thammasat University Hospital, Pathum Thani, Thailand. The participants were aged between 1-96 years old for screening purposes during the pandemic. The detection results and cycle threshold (Ct) values from each site were analyzed using McNemar’s test with a 95% confidence interval. Results Four participants had positive results. One patient tested positive only for the nasopharyngeal swab, whereas the other tested positive only for the tracheal secretion sample. No statistically significant difference was found between the discordant and concordant groups (P = 1). Conclusions We found two discordant results among the four positive cases in the 100 patients. One patient tested positive only from the nasopharyngeal swab, whereas the other tested positive only from the tracheal sample. The percentage of agreement was 98, and the kappa coefficient value was 65.64% (p <0.001). According to these results, one sample from the nasopharynx or tracheal tube should be sufficient to determine the infection status of low-risk patients. For highly suspicious cases, multisite sampling should be performed. This study showed discordance in COVID-19 RT-PCR screening results using samples from nasopharyngeal swabs and tracheal secretions in tracheotomized patients. A multiple-site sample is suggested for highly suspicious patients with tracheostomy.
in F1000Research on 2024-05-17 15:49:02 UTC.
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Background The “all-on-four” concept represents a significant advancement in dental implantology. particularly beneficial in cases of extensive jaw bone loss where invasive bone regeneration procedures are typically required. However, the successful implementation of this technique necessitates meticulous planning concerning implant selection, materials, and prosthesis design. The recent introduction of PEEK (Polyetheretherketone) in dentistry, especially in all-on-four prosthetics, prompts questions regarding its clinical efficacy and comparative biomechanical and biological advantages over conventional materials such as titanium and zirconia. While some studies have compared PEEK with other materials, systematic reviews evaluating its efficacy are scarce. This systematic review protocol intends to assess the evidence regarding the viability of PEEK as a potential alternative within the all-on-four approach in dental implantology. Methods This systematic review protocol will adhere to the Cochrane Handbook for Systematic Review of Interventions and align with the Methodological Expectations of the Cochrane Intervention Reviews (MECIR) guidelines. Utilizing a comprehensive search strategy, multiple databases, including PubMed, EMBASE, Scopus, EBSCO, Web of Science, Cochrane Central, and registries of clinical trials, will be explored. The search aims to identify randomized controlled trials and non-randomized studies investigating the application of PEEK in the all-on-four approach for dental procedures. Emphasizing clinically relevant outcomes such as implant survival, prosthesis success, peri-implant complications, and patient satisfaction, this review aims to provide insights into the effectiveness and potential benefits of using PEEK in all-on-four prosthetics. Non-randomized studies will be assessed for bias using ROBINS-I, while randomized controlled trials will undergo evaluation with the Cochrane Risk of Bias assessment tool, ROB II. Discussion The outcomes derived from this systematic review hold great significance for dental practitioners exploring the all-on-four concept. Understanding PEEK’s advantages and limitations compared to titanium and zirconia facilitates tailored treatment plans, enhancing success and satisfaction, ultimately improving dental care quality. Systematic review registration PROSPERO: CRD42024531175 (Registered on 13/04/2024).
in F1000Research on 2024-05-17 15:44:14 UTC.
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Background Next generation sequencing (NGS) has become a standard tool in the molecular diagnostics of Mendelian disease, and the precision of such diagnostics is greatly affected by the accuracy of variant calling from sequencing data. Recently, we have comprehensively evaluated the performance of multiple variant calling pipelines. However, no systematic analysis of the effects of read trimming on variant discovery with modern variant calling software has yet been performed. Methods In this work, we systematically evaluated the effects of adapters on the performance of 8 variant calling and filtering methods using 14 standard reference Genome-in-a-Bottle (GIAB) samples. Variant calls were compared to the ground truth variant sets, and the effect of adapter trimming with different tools was assessed using major performance metrics (precision, recall, and F1 score). Results We show that adapter trimming has no effect on the accuracy of the best-performing variant callers (e.g., DeepVariant) on whole-genome sequencing (WGS) data. For whole-exome sequencing (WES) datasets subtle improvement of accuracy was observed in some of the samples. In high-coverage WES data (~200x mean coverage), adapter removal allowed for discovery of 2-4 additional true positive variants in only two out of seven datasets tested. Moreover, this effect was not dependent on the median insert size and proportion of adapter sequences in reads. Surprisingly, the effect of trimming on variant calling was reversed when moderate coverage (~80-100x) WES data was used. Finally, we show that some of the recently developed machine learning-based variant callers demonstrate greater dependence on the presence of adapters in reads. Conclusions Taken together, our results indicate that adapter removal is unnecessary when calling germline variants, but suggest that preprocessing methods should be carefully chosen when developing and using machine learning-based variant analysis methods.
in F1000Research on 2024-05-17 15:38:06 UTC.
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Background White spot lesions (WSLs) are frequently linked with low microhardness and mineral content changes. several strategies have been employed to deal with these problems. This investigation aimed to analyze the microhardness and mineral content changes after remineralization with bioactive glass (BAG) and casein phospho-peptide-amorphous calcium phosphate with fluoride (CPP-ACPF). Methods Twenty sound maxillary first premolars extracted were used to obtain a total of one hundred enamel samples. forty enamel slabs were split into four experimental groups (n = 10 each): Group I, BAG; Group II, BAG+CPP-ACPF; Group III, CPP-ACPF varnish; and Group IV, artificial saliva (negative control). To create artificial WSLs, all samples were preserved in a prepared demineralizing agent for 72 h before treatment with remineralizing agents. Vickers microhardness test was performed. Additionally, 60 enamel samples were selected for analysis using energy dispersive spectroscopy (EDX) and assigned to six experimental groups; the first four groups were similar to that used in the microhardness test along with Group V: WSLs, and Group VI: baseline. The statistical analyses employed in this study included Tukey’s HSD (p<0.05), one-way ANOVA, and Shapiro-Wilk. Result Regarding surface microhardness, the BAG+CPP-ACPF group showed the most favorable recovery, which was better than the outcomes of the BAG and CPP-ACPF groups. A statistically significant change (p <0.05) was not observed between them. Similarly, for mineral content change, the BAG+CPP-ACPF group demonstrated the greatest result, The BAG group came next, and the CPP-ACPF group came last. Conclusion The BAG+CPP-ACPF group might be regarded as the best course of treatment for enhancing both the surface microhardness and mineral content (Ca, P), while the control group (Artificial saliva) showed the least satisfactory results in comparison. After demineralization, mineral content and microhardness decreased in all samples. Therefore, BAG+CPP-ACPF significantly improved the surface microhardness and mineral content.
in F1000Research on 2024-05-17 14:10:25 UTC.
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Plastic production is growing, plastic waste is accumulating, and current waste management methods (recycling, incineration, etc.) are not yet able to solve this waste problem. Proposals and projects aimed at solving or facilitating the problem of plastic waste are therefore relevant. This article proposes a deep geological disposal method for plastic waste projects. The prototype for this project was the deep geological disposal of nuclear waste. Although plastic waste and nuclear waste are fundamentally different, the adequacy of this approach is justified by the fact that plastic waste, such as nuclear waste, has a a long degradation period and poses great danger to the environment, animals, and humans. The article is conceptual and examines the aspects necessary for the implementation of the project, such as the establishment of a special international UN agency for plastic waste management, specific sources of funding, giving plastic waste a monetary value, applying free market principles, and using existing potential opportunities for deep geological disposal of plastic waste. This article also discusses the proposed concept for finding more optimal options.
in F1000Research on 2024-05-17 14:04:26 UTC.
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by Tong Liu, Hao Zhu, Zheng Wang
In the last few years, Micro-C has shown itself as an improved alternative to Hi-C. It replaced the restriction enzymes in Hi-C assays with micrococcal nuclease (MNase), resulting in capturing nucleosome resolution chromatin interactions. The signal-to-noise improvement of Micro-C allows it to detect more chromatin loops than high-resolution Hi-C. However, compared with massive Hi-C datasets available in the literature, there are only a limited number of Micro-C datasets. To take full advantage of these Hi-C datasets, we present HiC2MicroC, a computational method learning and then predicting Micro-C from Hi-C based on the denoising diffusion probabilistic models (DDPM). We trained our DDPM and other regression models in human foreskin fibroblast (HFFc6) cell line and evaluated these methods in six different cell types at 5-kb and 1-kb resolution. Our evaluations demonstrate that both HiC2MicroC and regression methods can markedly improve Hi-C towards Micro-C, and our DDPM-based HiC2MicroC outperforms regression in various terms. First, HiC2MicroC successfully recovers most of the Micro-C loops even those not detected in Hi-C maps. Second, a majority of the HiC2MicroC-recovered loops anchor CTCF binding sites in a convergent orientation. Third, HiC2MicroC loops share genomic and epigenetic properties with Micro-C loops, including linking promoters and enhancers, and their anchors are enriched for structural proteins (CTCF and cohesin) and histone modifications. Lastly, we find our recovered loops are also consistent with the loops identified from promoter capture Micro-C (PCMicro-C) and Chromatin Interaction Analysis by Paired-End Tag Sequencing (ChIA-PET). Overall, HiC2MicroC is an effective tool for further studying Hi-C data with Micro-C as a template. HiC2MicroC is publicly available at https://github.com/zwang-bioinformatics/HiC2MicroC/.
in PLoS Computational Biology on 2024-05-17 14:00:00 UTC.
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by Alexander Massey, Corentin Boennec, Claudia Ximena Restrepo-Ortiz, Christophe Blanchet, Samuel Alizon, Mircea T. Sofonea
Projects such as the European Covid-19 Forecast Hub publish forecasts on the national level for new deaths, new cases, and hospital admissions, but not direct measurements of hospital strain like critical care bed occupancy at the sub-national level, which is of particular interest to health professionals for planning purposes. We present a sub-national French framework for forecasting hospital strain based on a non-Markovian compartmental model, its associated online visualisation tool and a retrospective evaluation of the real-time forecasts it provided from January to December 2021 by comparing to three baselines derived from standard statistical forecasting methods (a naive model, auto-regression, and an ensemble of exponential smoothing and ARIMA). In terms of median absolute error for forecasting critical care unit occupancy at the two-week horizon, our model only outperformed the naive baseline for 4 out of 14 geographical units and underperformed compared to the ensemble baseline for 5 of them at the 90% confidence level (n = 38). However, for the same level at the 4 week horizon, our model was never statistically outperformed for any unit despite outperforming the baselines 10 times spanning 7 out of 14 geographical units. This implies modest forecasting utility for longer horizons which may justify the application of non-Markovian compartmental models in the context of hospital-strain surveillance for future pandemics.
in PLoS Computational Biology on 2024-05-17 14:00:00 UTC.
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by Brian P. H. Metzger
The relationship between genetic code robustness and protein evolvability is unknown. A new study in PLOS Biology using in silico rewiring of genetic codes and functional protein data identified a positive correlation between code robustness and protein evolvability that is protein-specific.
The relationship between genetic code robustness and protein evolvability is unknown. This Primer explores a new PLOS Biology study which uses in silico rewiring of genetic codes and functional protein data to identify a positive correlation between code robustness and protein evolvability that is protein-specific.
in PLoS Biology on 2024-05-17 14:00:00 UTC.
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by Masahiko Haruno
How third-party individuals respond to injustices is important for resolving conflict in society. A study in PLOS Biology shows that individuals experiencing acute stress prefer to aid victims over punishing offenders, an opposite pattern to non-stress conditions.
How third-party individuals respond to injustices is important for resolving conflict in society. This Primer explores a new study that shows that individuals experiencing acute stress prefer to aid victims over punishing offenders, an opposite pattern to non-stress conditions.
in PLoS Biology on 2024-05-17 14:00:00 UTC.
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In healthcare, improvement leaders have been inspired by the frameworks from industry which have been adapted into control systems and certifications to improve quality of care for people. To address the challenge to regain trust in healthcare design and delivery, we propose a conceptual framework, i.e. the “House of Trust”. This House brings together the Juran Trilogy, the emerging concept of co-production in quality management and the multidimensional definition of quality, which describes core values as an integral part of the system to deliver person- and kin-centered care. In the “House of Trust” patients, their kin, healthcare providers, executives and managers feel at home, with a sense of belonging. If we want to build a care organization that inspires and radiates confidence to all stakeholders, highlighting the basic interactions between front- and back-office is required. An organization with both well-organized back- and front-offices can enable all to benefit from the trust each of them needs and deserves. A quality system does not depend on government inspection and regulations nor on external accreditation to develop itself into a House of Trust. Success will only be achieved if all involved continuously question themselves about the technical dimensions of quality and their core values during the “moment of truth”.
in F1000Research on 2024-05-17 13:39:09 UTC.
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Background T2-weighted hyperintensities in the spinal cord are a complex and diagnostically challenging entity that can present with diverse clinical features. This study protocol outlines a comprehensive investigation to understand the causes, clinical and imaging characteristics, and correlation with pathological findings of T2-weighted hyperintensities in the spinal cord. By establishing a systematic assessment approach, this study seeks to provide valuable insights into these abnormalities’ diagnostic and prognostic implications. Methods The study will be conducted as a prospective observational design. Patients with clinically diagnosed or suspected spinal cord injury presenting with intramedullary T2-weighted hyperintensity and referred for MRI evaluation will be included. Data collection will encompass patient demographics, clinical features, and extensive imaging parameters. Pathological data, when available, will be correlated with imaging findings. Various statistical methods will be employed to analyse the data, including frequency analysis, comparative tests, logistic regression, and survival analysis. Expected Results The study anticipates elucidating the spectrum of etiologies underlying T2-weighted hyperintensities in the spinal cord and their clinical and imaging profiles. The systematic approach will offer a structured diagnostic method, while correlations with pathological data will provide an enhanced understanding of these conditions. The results are expected to provide clinicians with valuable insights into diagnosing, treating, and prognosticating patients with spinal cord hyperintensities.
in F1000Research on 2024-05-17 12:25:45 UTC.
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The likelihood of being hit by the likelihood of experiencing lightning within a year was approximately 1 in 960,000. Despite this alarming statistic, it is reassuring to know that the chances of surviving a lightning strike are relatively high; around 90% of people who are struck by lightning manage to survive. Lightning-caused ophthalmic injuries are caused by heat that can be generated through the direct or indirect flow of electric current, and by resistance and shock waves caused by heat. Electrical burn injuries rarely cause ocular complications, since the initial burn is typically fatal. We present a case of lightning injury that affected the eyes. and its treatment and a brief overview of the literature on the subject.
in F1000Research on 2024-05-17 12:23:01 UTC.
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The Neuroscientist, Ahead of Print.
The existence of neurogenesis in the adult human hippocampus has been under considerable debate within the past three decades due to the diverging conclusions originating mostly from immunohistochemistry studies. While some of these reports conclude that hippocampal neurogenesis in humans occurs throughout physiologic aging, others indicate that this phenomenon ends by early childhood. More recently, some groups have adopted next-generation sequencing technologies to characterize with more acuity the extent of this phenomenon in humans. Here, we review the current state of research on adult hippocampal neurogenesis in the human brain with an emphasis on the challenges and limitations of using immunohistochemistry and next-generation sequencing technologies for its study.
in The Neuroscientist on 2024-05-17 12:21:53 UTC.
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Background Helicobacter pylori and intestinal parasites are well-known for their high prevalence in children, especially in developing countries. However, their concomitant infections are poorly documented. In this study, we aimed to evaluate the association between intestinal parasites and H. pylori among hospitalized children and adolescents with upper gastrointestinal complaints in Northern Lebanon. Methods A cross-sectional study was conducted involving 297 hospitalized pediatric patients, aged between 1 and 15 years, who presented with gastrointestinal symptoms. The socio-demographic, lifestyle, and gastrointestinal characteristics of all participants were analyzed. Fresh stool samples were collected and screened for the presence of intestinal parasites and H. pylori infections. Results 6.4% of the patients were positive for intestinal parasitic infections, 5.4% were positive for H. pylori infection, and 11.8% were co-infected. The results of the Chi-square test showed that H. pylori infection is significantly associated with parasitic infection but not with a particular species. The most frequent coinfection was H. pylori-Entamoeba histolytica (77.1%). Moreover, H. pylori infection was associated with overcrowding and infrequent washing of vegetables before eating. The prevalence of co-infections increased in patients of mothers with a primary educational level or less. In regards to clinical characteristics, our findings showed a statistically significant relationship between i) gastric reflux and H. pylori, and ii) severe diarrhea and parasitic infection. Conclusion Our data highlighted the association between H. pylori and intestinal parasitic infections. Thus, H. pylori detection could be taken into consideration while screening for parasitic infections in children and adolescents.
in F1000Research on 2024-05-17 12:20:45 UTC.
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Background Soda lakes are habitats characterized by haloalkaline conditions also known to host unique microbial communities. The water chemistry changes with seasons due to evaporative concentration or floods from the surrounding grounds. However, it is not yet clear if the change in physiochemical changes influences the spatiotemporal diversity and structure of microbial communities in these ecosystems. Methods Using 16S rRNA gene amplicon sequencing, we investigated the diversity and structure of microbial communities in water and brine samples taken from Lake Magadi between June and September 2018. Additionally, physicochemical parameters were also analyzed for every sampling site. Additionally, physicochemical parameters were also analyzed for every sampling site. Results The abundant bacterial phyla were Proteobacteria, Cyanobacteria, Bacteroidetes, Actinobacteria, Firmicutes, Verrumicrobia, Deinococcus-Thermus, Spirochaetes, and Chloroflexi. The Archaeal diversity was represented by phyla Euryachaeota, Crenarchaeota, Euryarchaeota, and Thaumarchaeota. The dominant bacterial species were: Euhalothece sp. (10.3%), Rhodobaca sp. (9.6%), Idiomarina sp. (5.8%), Rhodothermus sp. (3.0%), Roseinatronobacter sp. (2.4%), Nocardioides sp. (2.3%), Gracilimonas sp. (2.2%), and Halomonas sp. (2%). The dominant archaeal species included Halorubrum sp. (18.3%), Salinarchaeum sp. (5.3%), and Haloterrigena sp. (1.3%). The composition of bacteria was higher than that of archaea, while their richness and diversity varied widely across the sampling seasons. The α-diversity indices showed that high diversity was recorded in August, followed by September, June, and July in that order. The findings demonstrated that temperature, pH, P+, K+, NO3 -, and total dissolved solids (TDS) contributed majorly to the diversity observed in the microbial community. Multivariate analysis revealed significant spatial and temporal effects on β-diversity and salinity and alkalinity were the major drivers of microbial composition in Lake Magadi. Conclusions We provide insights into the relationships between microbial structure and geochemistry across various sampling sites in Lake Magadi.
in F1000Research on 2024-05-17 12:15:50 UTC.
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Background Learning apps can be helpful to non-native language learners in learning Arabic, which includes speaking, writing, and speaking exercises. When learners become better in the language, they become more confident in interacting with the community, thus affecting their Cultural Intelligence (CQ) and Acculturation (AC). This study aimed to explore the relationship between the CQ and AC among non-native learners of Arabic. Additionally, the study aimed to investigate the potential impacts of learning apps and gender. Methods This study used a correlational approach, involving a sample of 102 non-native Arabic language learners in Jordan. To assess these factors, this study used the Cultural Intelligence Scale and the Acculturation Survey. Results The findings of this study revealed a positive correlation between the CQ and AC. Furthermore, the use of apps can provide CQ and AC levels. In addition, the study determined that gender did not play a significant role in influencing learners. Conclusion the utilization of educational apps has been shown to enhance both CQ and AC. Thus, it is imperative to encourage learners to engage with these apps, as they foster cultural awareness, thereby facilitating the process of learning Arabic.
in F1000Research on 2024-05-17 12:08:09 UTC.
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Objective To compare iodine density (ID) and contrast-enhanced attenuation value (CEAV) from dual-layer spectral computed tomography (DLSCT) scans of lymphomatous, metastatic squamous cell carcinoma (SCCA), and normal cervical lymph nodes. Methods Data including ID and CEAV were retrospectively collected from patients who underwent DLSCT of the neck between January 2020 and August 2023. Results from each group (lymphomatous, metastatic SCCA, and normal) were compared and analyzed using one-way ANOVA and receiver operating characteristic curve. Results 129 cervical lymph nodes were collected from patients who met the inclusion criteria (50, 41, and 38 nodes from the lymphomatous, metastatic SCCA, and normal group, respectively). The mean ID of lymphomatous, metastatic SCCA, and normal nodes was 1.01±0.27, 1.36±0.28, and 1.45±0.29 mg/mL, respectively. Comparing lymphomatous nodes with metastatic SCCA nodes, the lymphomatous nodes had significantly lower values of ID (p<0.002) and CEAV (p<0.001). Similarly, when comparing lymphomatous nodes with normal nodes, the lymphomatous nodes had significantly lower values of ID (p<0.001) and CEAV (p<0.001). The optimal ID cut-off value for distinguishing between lymphomatous and metastatic SCCA nodes was 1.175 mg/ml (specificity of 84.2%, sensitivity 77.8%, AUC 0.788, P = 0.003). The optimal CEAV cut-off value was 77.5 HU (specificity 88.9%, sensitivity 78.9%, AUC 0.851, P<0.001). Conclusions The ID and CEAV measurements from DLSCT were significantly different between lymphomatous, metastatic SCCA, and normal lymph nodes. These findings indicate that DLSCT can be used to distinguish between these conditions in the diagnosis of cervical lymph nodes.
in F1000Research on 2024-05-17 12:04:58 UTC.
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Background Respiratory syncytial virus (RSV) is one of the most significant respiratory pathogens that causes acute lower respiratory tract infections (LRTI) early in life. Most children have a history of RSV infection within 24 months of age, and recurrent infections are common throughout life. Methods Children under five years of age were identified through a review of medical records with a diagnosis of RSV-LRTI between 2016 and 2020. Severe RSV-LRTI was defined as a prolonged length of stay (> 7 days), admission to the intensive care unit, need for mechanical ventilation, non-invasive positive pressure ventilation, or in-hospital mortality. Factors associated with severe RSV-LRTI were investigated using univariate and multivariate analyses. Results During the study period, 620 patients were diagnosed with RSV-LRTI and 249 (40.16%) patients had severe RSV-LRTI. In the multivariable logistic regression analysis, the factors for severe RSV-LRTI were being under 3 months (aOR 2.18 CI 1.39-3.43, p0.001), cardiovascular disease (aOR 3.55 CI 1.56-8.06, p0.002), gastrointestinal disease (aOR 5.91 CI 1.90-18.46, p0.002), genetic disease (aOR 7.33 CI 1.43-37.54, p0.017), and pulmonary disease (aOR 9.50, CI 4.56-19.80, p<0.001). Additionally, the presence of ≥ 2 co-morbidities (aOR 6.23 CI 2.81-14.81, p<0.016), experiencing illness for more than 5 days (aOR 3.33 CI 2.19-5.06, p<0.001), co-detection of influenza (aOR 8.62 CI 1.49-38.21, p0.015), and nosocomial RSV infection (aOR 9.13 CI 1.98-41.30, p0.012), markedly increased the risk of severe RSV-LTRI. The severe RSV-LRTI group demonstrated higher hospitalization expenses (median, US $720.77 vs $278.00, respectively; p<0.001), and three infants died in-hospital. Conclusion Children at high risk for RSV-LRTI due to underlying genetic and gastrointestinal diseases are at an increased risk for severe RSV-LRTI. Further studies to determine the cost-effectiveness of RSV immunization in these potential co-morbidities should be initiated to prioritize RSV immunization, especially in resource-constrained regions with limited availability of nirsevimab.
in F1000Research on 2024-05-17 11:24:24 UTC.
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Background Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) mainly affects the respiratory tract, but different organs may be involved including the kidney. Data on acute kidney injury (AKI) in critical forms of coronavirus disease 2019 (COVID-19) are scarce. We aimed to assess the incidence, risk factors and prognostic impact of AKI complicating critical forms of COVID-19. Methods A retrospective descriptive case/control monocentric study conducted in a medical intensive care unit of a tertiary teaching hospital over a period of 18 months. Results We enrolled 144 patients, with a mean age of 58±13 years old and a male predominance (sex-ratio: 1.25). Forty-one (28%) developed AKI within a median of 4 days (Q1: 3, Q3: 8.5) after hospitalization. It was staged KDIGO class 3, in about half of the cases. Thirteen patients underwent renal replacement therapy and renal function improved in seven cases. Diabetes (OR: 6.07; 95% CI: (1,30-28,4); p: 0.022), nephrotoxic antibiotics (OR: 21; 95% CI: (3,2-146); p: 0.002), and shock (OR: 12.21; 95% CI: (2.87-51.85); p: 0.031,) were the three independent risk factors of AKI onset. Mortality was significantly higher in AKI group (OR: 3.94; 95% CI: (1.65-9.43); p<10−3) but AKI didn’t appear to be an independent risk factor of poor outcome. In fact, age (p: 0.004), shock (p: 0.045) and MV (p<10−3) were the three prognostic factors in multivariate analysis. Conclusions The incidence of AKI was high in this study and associated to an increased mortality. Diabetes, use of nephrotoxic antibiotics and shock contributed significantly to its occurrence. This underlines the importance of rationalizing antibiotic prescription and providing adequate management of patients with hemodynamic instability in order to prevent consequent AKI.
in F1000Research on 2024-05-17 11:17:41 UTC.
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Background The Indian government is committed to address various manifestations of malnutrition, including overweight and obesity, inorder to improve individual health and well-being. The scoping review aims to map existing national policy instruments (programmes, schemes, regulations and guidelines) addressing overweight and obesity in India and analysing them for Social and Behaviour Change Communication (SBCC) strategies. Methods Systematic identification and selection of policy instruments using ‘Arksey and O’Malley’ framework was conducted from central government ministry websites, between March and June 2023. These instruments focused on nutrition and/or physical activity, targeting specific demographic groups like pregnant women, lactating mothers, children (0-5 years and 5-9 years), or adolescents (10-19 years); excluding those focusing on specific diseases like micronutrient deficiencies, wasting, and stunting. Based on search strategy six policy instruments were included and analysed for SBCC strategies. Results While many policy instruments incorporated SBCC plans; the ‘National Programme for Prevention of Non-Communicable Diseases (NP-NCD)’ stands out as a significant policy initiative specifically targeting the prevention of overweight and obesity within the broader context of Non-Communicable Diseases. It adopts a comprehensive approach addressing key drivers contributing to overweight/obesity across multiple levels of behavioural influence i.e., individual, interpersonal, community and organisation for health promotion. However, there’s need to strengthen SBCC strategies related to prevention and management of obesity, especially screening and counselling, to cover all age groups with a particular focus on adolescents and youth. SBCC strategies can also be incorporated into India’s Integrated Nutrition Support Programme (POSHAN 2.0) and/or Reproductive, Maternal, New-born, Child, Adolescent Health and Nutrition (RMNCAH+N) under the National Health Mission. Conclusion This paper underscores the necessity for comprehensive strategies to address multifaceted origin of overweight and obesity. The NP-NCD stands out as a noteworthy initiative, and there is considerable potential for other programmes to emulate it SBCC strategies to bolster their overall effectiveness. Note : *Policy instrument’s throughout the paper has been used to cover programmes, schemes, regulations and guidelines.
in F1000Research on 2024-05-17 11:14:39 UTC.
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Background Periodontal disease is a chronic inflammatory disease of structures surrounding the teeth. Its etiology is multifactorial. The primary etiological factor is the microbial component; the other factors are systemic, behavioral, environmental, and psychological. Conventional management includes routine periodontal therapy involving prophylactic and surgical management. In developing countries like India, complementary medicine and alternative medicines like yoga are gaining popularity for improving systemic health. Hence this pilot study was designed to assess the psychometric properties of a structured questionnaire that can assess knowledge, attitude, and practice (KAP) regarding the impact of yoga on oral and periodontal health in Indian population. Methods The KAP questionnaire was developed (Stage One) using a deductive approach, and a psychometric evaluation of the questionnaire was performed to evaluate it’s reliability and validity (Stage Two). Initial content validation and test re-test reliability were assessed using kappa statistics with binary responses. An intraclass correlation coefficient (ICC) was used to assess the questions in the practice and attitude category with categorical variables. Further assessment of psychometric properties of the questionnaire was done using item response theory. The developed questionnaire had four principal sections: demography of participants; knowledge regarding yoga and oral health; attitude towards yoga and oral health; and practice towards implementing yoga for oral health. Results The ICC for all the assessed questions was greater than 0.60 suggesting satisfactory stability. Internal consistency measured using Cronbach’s alpha for knowledge, attitude, and practice items were reported to be 0.632, 0.923, and 0.591 respectively and that of the KAP total was 0.632. Conclusions The findings of this study showed that the questionnaire had an acceptable psychometric property for measuring KAP regarding yoga and it’s role in oral and periodontal health among Indian adults. The analysis of participant responses revealed that they had a medium level of knowledge regarding yoga and periodontal disease.
in F1000Research on 2024-05-17 11:11:12 UTC.
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Curculigo latifolia Dryand. ex W. T. Aiton, from the genus Curculigo, is a medicinal plant traditionally used to treat numerous illnesses such as fever, stomach aches, jaundice, wounds, and inflammation. C. latifolia is a perennial herb that is widely found in tropical and subtropical regions, such as Southeast Asia, Southern China, Bangladesh, Australia, and the Andaman Islands. This review collates the reported studies on the different aspects of C. latifolia from its plant description, nutritional value, phytochemistry, chemical composition, and pharmacological properties. This review aims to identify gaps in the literature and provide useful references for future work on this plant. Previous studies have shown that C. latifolia contains high mineral contents of calcium, iron, and magnesium, which are essential components of human health. Moreover, the plant is rich in phytochemicals, which play a prominent role in various pharmacological activities. The most common compounds identified included curculigoside, crassifoside I, nyasicoside, and curculigine. C. latifolia demonstrated high antioxidant activity through its ability to scavenge superoxide anions, 1,1–diphenyl–2–picrylhydrazyl (DPPH) and 2,2’-azino–bis(3–ethylbenzthiazoline–6–sulfonic acid) (ABTS) radicals, reducing ferric ions to ferrous complexes, iron chelation, and B-carotene bleaching. It was also shown that the roots, stems, and leaves of C. latifolia were effective in exerting antimicrobial activity against several microbial strains, including Bacillus cereus, Bacillus subtillis, Enterobacter aerogenes, Erwinia sp., Klebsiella sp., Pseudomonas sp., Candida albicans, Salmonella choleraesuis and Staphylococcus aureus. Moreover, the root, fruit, leaf, petiole, and rhizome extracts were found to improve glucose uptake and insulin secretion in diabetic rats, suggesting their antidiabetic potential. C. latifolia presents a wide range of medicinal properties that could make it a promising functional food or source of food supplements to prevent nutrition–related or chronic diseases.
in F1000Research on 2024-05-17 11:10:52 UTC.
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Background Current treatment of osteoarthritis (OA) mainly focused on treating symptoms. Exosome from Adipose-derived Mesenchymal Stem Cell (Ad-MSC) have been shown to delay degenerative process. This study aimed to investigate the clinical, radiological and histological impact of combined intra-articular (IA) hyaluronic acid (HA) and exosome Ad-MSCs in-vivo using a larger animal model with low-grade OA. Methods Eighteen male Ovies aries sheep underwent total lateral meniscectomy and conventional radiography was performed to confirm low-grade OA after 6 weeks. The sheep were divided into three groups, Group 1 (G1; n=6) received thrice exosome injections, G2 (n=6) received twice HA injection, and G3 (n=6) received both treatments with a 1-week interval after 10 days of meniscectomy. Clinical evaluations were conducted using the Clinical Lameness Score (CLS), radiographic with X-ray using OA score by Innes et al, while macroscopic evaluation by Osteoarthritis Research Society International (OARSI) scores. Results Lameness parameter scored lowest in G3 significantly (2.0±0.0 VS 2.7±0.52 VS 2.7±0.52; p=0.024) at the second month although the overall CLS score did not significantly differ at the 3rd month. The best improvement of conventional total OA radiographic score at the 3rd month compared to all groups (5.2±1.17 vs 6.3±0.82 vs 6.7±1.03; p=0.053). Macroscopic OARSI evaluation showed no difference (p=0.711). Conclusions Combined repeated exosome Ad-MSC and HA IA injection proven to delay OA progression, however longer duration of follow up is required to evaluate its long-term effect.
in F1000Research on 2024-05-17 10:46:14 UTC.
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Background Patient-related factors and limited medication adherence in patients with chronic diseases, are associated with poor clinical outcomes, long-term complications, and increased overall disease costs. Many methods have been tested with mixed results, and innovative approaches are needed to encourage patients to adhere to their prescribed drug regimens. Methods This randomised controlled trial examined a new multifactorial pharmacist-led intervention protocol (MPIP), including a medication therapy management (MTM) program with face-to-face counselling, patient-specific medication booklets, and a mobile application, from July 2021 to September 2022 in the Oud Al Touba diagnostic and screening ambulatory centre in 192 patients with type 2 diabetes in the United Arab Emirates. Medication adherence was assessed using the fixed medication possession ratio of medication refills and the medication adherence questionnaire. Results At 12 months follow-up, participants in the MPIP showed significant improvement in overall medication adherence with total (composite) medication possession ratio (MPRt) of mean (±SD) 0.95 (±0.09) compared to 0.92 (± 0.09) in the control group with mean difference of 0.03 (95%, CI 0.01–0.06), P =0.02. In addition, improvement trend was evident in the MPIP group for all medication regimens with P value <0.01. Comparable results were noticeable in adherence questionnaire scores at the end of the study, with 66 participants in the intervention group scored zero on the questionnaire, suggesting high adherence to medication compared to the control group (48 participants only). The MTM program performed 41 clinical interventions on drug-related problems, compared to six interventions in the control group, and the use of mobile application and medication booklet have increased to 45.7% compared to 21.4% before study exit. Conclusions The pharmacy intervention protocol effectively improved medication adherence and optimised medication regimens in diabetic patients with chronic medication regimens in an ambulatory healthcare centre.
in F1000Research on 2024-05-17 10:42:45 UTC.
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Background This study aimed to examine individual- and health service provider-related factors that influence the self-management behavior of patients with stroke. Methods This cross-sectional study investigated a cohort of 110 ischemic stroke patients in the neurology outpatient department of Universitas Airlangga Hospital from February 2023 to May 2023. Data were obtained using the following three distinct questionnaires: the general demographic questionnaire, health care provider questionnaire, and modified stroke self-management behavior questionnaire. Results Chi-square test results indicated a significant correlation between age (p = 0.023) and information availability (p = 0.000) with self-management behavior in patients with stroke. However, no significant correlations were observed between gender (p = 1.107), residence (p = 0.859), availability of access (p = 0.093), availability of health facilities (p = 0.065), and collaboration among health workers (p = 0.641) with self-management behavior in patients with stroke. Ordinal logistic regression analysis results indicated that age significantly influenced self-management behavior in patients with stroke (p = 0.034; OR = 2.49). Discussion The presence of reliable information within the hospital setting is expectedly complemented by a strong level of literacy among patients with stroke, thereby facilitating the enhancement of their self-management practices.
in F1000Research on 2024-05-17 10:41:39 UTC.
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Background Research and researchers are heavily evaluated, and over the past decade it has become widely acknowledged that the consequences of evaluating the research enterprise and particularly individual researchers are considerable. This has resulted in the publishing of several guidelines and principles to support moving towards more responsible research assessment (RRA). To ensure that research evaluation is meaningful, responsible, and effective the International Network of Research Management Societies (INORMS) Research Evaluation Group created the SCOPE framework enabling evaluators to deliver on existing principles of RRA. SCOPE bridges the gap between principles and their implementation by providing a structured five-stage framework by which evaluations can be designed and implemented, as well as evaluated. Methods SCOPE is a step-by-step process designed to help plan, design, and conduct research evaluations as well as check effectiveness of existing evaluations. In this article, four case studies are presented to show how SCOPE has been used in practice to provide value-based research evaluation. Results This article situates SCOPE within the international work towards more meaningful and robust research evaluation practices and shows through the four case studies how it can be used by different organisations to develop evaluations at different levels of granularity and in different settings. Conclusions The article demonstrates that the SCOPE framework is rooted firmly in the existing literature. In addition, it is argued that it does not simply translate existing principles of RRA into practice, but provides additional considerations not always addressed in existing RRA principles and practices thus playing a specific role in the delivery of RRA. Furthermore, the use cases show the value of SCOPE across a range of settings, including different institutional types, sizes, and missions.
in F1000Research on 2024-05-17 10:41:20 UTC.
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Background Numerous systematic reviews and meta-analyses have sought to clarify the relationship between greenspace exposure and health outcomes, but the results are inconsistent. We aimed to synthesise all relevant systematic reviews and meta-analyses on this association. Methods We searched five databases (PubMed, Embase, the Cumulative Index to Nursing and Allied Health Literature (CINAHL), Scopus, and the Cochrane Database of Systematic Reviews) and conducted a manual reference search for systematic reviews and meta-analyses written in English and published in peer-reviewed journals that used clearly defined measures of greenspace exposure and reported health outcomes directly attributable to greenspace exposure. A total of 36 systematic reviews published between January 2010 and December 2020 were identified for inclusion in this systematic review of reviews (PROSPERO: CRD42021227422). An updated review is underway, and the protocol is published in PROSPERO (CRD42022383421). The methodological quality and risk of bias of included systematic reviews were evaluated using the AMSTAR-2 and ROBIS tools, respectively. Results Beneficial effects of greenspace exposure were observed for all-cause and cardiovascular disease mortality, and mental health and cognitive function. Ambivalent results were found for cardiovascular and metabolic health, general health and quality of life (QOL), and respiratory health and allergies. Most of the systematic reviews included in the current umbrella review had a low to moderate methodological quality and a high risk of bias. Conclusions This umbrella review highlights the link between greenspaces and a variety of health outcomes, emphasising the importance of preserving existing greenspaces and integrating additional vegetation into urban areas to maintain public health.
in F1000Research on 2024-05-17 10:40:04 UTC.
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Next-generation sequencing (NGS) has enabled analysis of rare and uncommon variants in large study cohorts. A common strategy to overcome these low frequencies and/or small effect sizes relies on collapsing strategies, i.e. to bin variants within genes/regions. Several tools are now available for advanced statistical analyses; however, tools to perform basic tasks such as obtaining allelic counts within defined gene/region boundaries are unavailable or require complex coding. GARCOM (“Gene And Region Count Of Mutations”) library, an open-source freely available package in R language, returns a matrix with allelic counts within genes/regions per sample. GARCOM accepts input data in PLINK or VCF formats, with additional options to subset data for refined analyses.
in F1000Research on 2024-05-17 10:34:59 UTC.
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Objectives This study aims to provide a comprehensive overview of the role of quadratic polynomials in data modeling and analysis, particularly in representing the curvature of natural phenomena. Methods We begin with a fundamental explanation of quadratic polynomials and describe their general forms and theoretical significance. We then explored the application of these polynomials in regression analysis, detailing the process of fitting quadratic models to the data using Python libraries NumPy and Matplotlib. The methodology also included calculation of the coefficient of determination (R-squared) to evaluate the polynomial model fit. This study utilizes illustratively generated data to demonstrate the application of quadratic polynomials in Python for robust data analysis. Results Using practical examples accompanied by Python scripts, this study demonstrated the application of quadratic polynomials to analyze data patterns. These examples illustrate the utility of quadratic models in applied analytics. Conclusions This study bridges the gap between theoretical mathematical concepts and practical data analysis, thereby enhancing the understanding and interpretation of the data patterns. Furthermore, its implementation in Python, released under MIT’s license, offers an accessible tool for public use.
in F1000Research on 2024-05-17 10:29:53 UTC.
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Background People who have had a stroke or a Transient Ischaemic Attack (TIA) can experience psychological and/or cognitive difficulties. The body of research for psychological and neuropsychological interventions after stroke is growing, however, published systematic reviews vary in scope and methodology, with different types and severity of strokes included, and at times, diverse conclusions drawn about the effectiveness of the interventions evaluated. In this umbrella review, we aim to systematically summarise the existing systematic reviews evaluating psychological interventions for mood and cognition post-stroke/TIA. Methods We will conduct this umbrella review according to the JBI Manual for Evidence Synthesis. The following databases will be searched from inception: Cochrane Database of Systematic Reviews, Database of Reviews of Effects (DARE), MEDLINE, Embase, CINAHL, PsycINFO, and Epistemonikos. Systematic reviews with or without meta-analysis published until the search date will be included. Reviews including psychological interventions addressing mood and/or cognition outcomes for any stroke type or severity will be screened for eligibility. A narrative synthesis, including content analysis, will be used. Each stage of the review will be processed by two independent reviewers and a third reviewer will be considered to resolve disagreements. The methodological quality of the included reviews will be assessed using AMSTAR 2. Discussion Existing systematic reviews provide varied evidence on the effectiveness of psychological interventions post-stroke/TIA. This umbrella review aims to summarise knowledge and evidence on different types of psychological and neuropsychological interventions targeting mood and cognition. Findings will highlight important knowledge gaps and help prioritise future research questions. Systematic Review Registration This protocol was prospectively registered with the International Prospective Register of Systematic Reviews (PROSPERO) on November 15, 2022; PROSPERO CRD42022375947.
in F1000Research on 2024-05-17 10:21:53 UTC.
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Background The prevalence of diabetes mellitus (DM) is increasing overtime, potentially leading to various severe health complications and mortality. Despite therapeutic agents have currently been developed, unexpected adverse effects are inevitable. Hence, safe and effective medications such as those of plant origin are critical to prevent unexpected complication in DM sufferers. Etlingera elatior has been widely used as spice and traditional medicine to treat diabetes in Aceh Province, Indonesia. However, study regarding α-glucosidase inhibitory effect of E. elatior growing in Gayo highlands, Aceh, Indonesia, is completely lacking. The aim of this study was to evaluate in vitro α-glucosidase inhibitory effect of E. elatior ethanol extracts (EEEE) growing in Gayo highlands, Aceh Province, Indonesia. Methods Antioxidant activity was determined using DPPH procedure, whereas α-glucosidase inhibition assay was carried out using spectrophotometric method. Data analysis was performed using One-Way Analysis of Variance (ANOVA), followed by Duncan’s multiple range test at α=0.05. Results Phytochemical analysis revealed the presence of total phenolic (TPC), total flavonoid (TFC), and total tannin (TTC) content in all E. elatior plant parts, in which the highest TPC was found in the stem (158.38 GAE/g), whereas the highest TFC and TTC was obtained in the rhizome extracts. The extract of fruit showed the strongest antioxidant activities, followed by the stem and leaf, with IC50 of 2.381 μg/mL, 6.966 μg/mL, and 19.365 μg/mL, respectively. All E. elatior extracts revealed a significant inhibitory activity against α-glucosidase at the concentration of 500 μg/mL, in which the stem extract showed the most effective α-glucosidase inhibitory effect with IC50 value of 5.15 μg/mL, suggesting its promising potential as antidiabetic agent. Conclusions This study highlights E. elatior potency as a novel source of antioxidant and natural antidiabetic compounds that are useful for the prevention and treatment of diabetes.
in F1000Research on 2024-05-17 10:08:44 UTC.
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Introduction The COVID-19 pandemic affected people’s health behaviours and health outcomes. Political or affective polarization could be associated with health behaviours such as mask-wearing or vaccine uptake and with health outcomes, e.g., infection or mortality rate. Political polarization relates to divergence or spread of ideological beliefs and affective polarization is about dislike between people of different political groups, such as ideologies or parties. The objectives of this study are to investigate and synthesize evidence about associations between both forms of polarization and COVID-19 health behaviours and outcomes. Methods In this systematic review, we will include quantitative studies that assess the relationship between political or affective polarization and COVID-19-related behaviours and outcomes, including adherence to mask mandates, vaccine uptake, infection and mortality rate. We will use a predetermined strategy to search EMBASE, Medline (Ovid), Cochrane Library, Cochrane COVID-19 Study Register, Global Health (Ovid), PsycInfo (Ovid), Web of Science, CINAHL, EconLit (EBSCOhost), WHO COVID-19 Database, iSearch COVID-19 Portfolio (NIH) and Google Scholar from 2019 to September 8 2023. One reviewer will screen unique records according to eligibility criteria. A second reviewer will verify the selection. Data extraction, using pre-piloted electronic forms, will follow a similar process. The risk of bias of the included studies will be assessed using the JBI checklist for analytical cross sectional studies. We will summarise the included studies descriptively and examine the heterogeneity between studies. Quantitative data pooling might not be feasible due to variations in measurement methods used to evaluate exposure, affective and political polarization. If there are enough relevant studies for statistical data synthesis, we will conduct a meta-analysis. Discussion This review will help to better understand the concept of polarization in the context of the COVID-19 pandemic and might inform decision making for future pandemics. Protocol registration PROSPERO ID: CRD42023475828.
in F1000Research on 2024-05-17 10:07:41 UTC.
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Background Sleep can be defined as a state of reduced attention from where the person can be woken up by any kind of stimuli. Sleep difficulties are a major group of disorders affecting one third of the adult population. The present study was taken up to assess the sleep quality and prevalence of sleep disorders among the adult population in the urban slum area of H Siddaiah Road Urban Primary Health Center (UPHC), which is in the Urban Field Practice Area, BMCRI. Methods Stratified random sampling was used to select 821 adults in the population of 18-60 years of age. Ethical clearance was obtained from the Institutional Ethical Committee. A pretested semi-structured questionnaire was used to interview the adults after obtaining their consent. The data was entered in Microsoft Office Excel and analysed using SPSS ver20.0. Results The study population was 52.81% females and 77.5% in the age group of 18-30 years. Most of the study population were Hindus (78.90%), and only 3.8% of the study population were illiterate. Most of them were employed (86.12%). Substance use was present in 82.9% of the study participants and overcrowding was present in 51.3% of the subjects. Female gender, being unemployed, living with relatives, overcrowding, and substance use such as alcohol and smokeless tobacco were the factors associated with poor sleep quality as measured using the Pittsburgh Sleep Quality Index. Among the study participants having poor sleep quality, most of participants needed further clinical assessment for insomnia (86%) followed by assessment for sleep apnoea (50.5%). Conclusions 200 (24.36%) study participants were determined to have poor sleep quality. Gender, marital status and overcrowding were the factors associated with poor sleep quality. A significant number of study participants need further assessment on insomnia, sleep apnoea and psychiatric disorders.
in F1000Research on 2024-05-17 10:05:15 UTC.
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Glioblastoma (GBM), known for its aggressive behavior and dismal prognosis. Traditional therapeutic methods, including adjuvant chemotherapy and radiotherapy in conjunction with maximally safe surgical resection, are designed to prolong survival and alleviate symptoms. This case report investigates the relationship between survival outcomes in glioblastoma patients and gross total resection (GTR). A recurring seizure disorder manifested in a 58-year-old female patient presented with left-sided lower limbs weakness and occurred twice weekly for a maximum duration of 20 seconds; this condition necessitated hospitalisation and subsequent surgical intervention. A gross total resection was executed with success, resulting in the accomplishment of complete tumor excision. The patient received radiotherapy after a six-week regimen of temozolomide chemotherapy that followed the surgical removal of tumor. Notably, following treatment, the patient reported a substantial amelioration of symptoms and has maintained a 24-month survival rate thus far, with continuous follow-up. This case highlights the potential for enhanced survival outcomes in the treatment of glioblastoma when gross total resection (GTR) is followed by adjuvant chemo-radiotherapy.
in F1000Research on 2024-05-17 10:02:38 UTC.
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Background Patient-reported outcome measures (PROMs) are essential for assessing the health of patients with chronic venous disease (CVD). Therefore, we aimed to translate the Aberdeen Varicose Vein Questionnaire into Thai language (AVVQ-Thai) and evaluate its reliability and validity. Minimal clinically important differences (MCID) of the AVVQ-Thai also be estimated. Methods International standards for PROM translation were followed including the forward-backwards translation of the AVVQ. Patients with Clinical-Etiology-Anatomy-Pathophysiology (CEAP) C2-C6 with truncal reflux were prospectively included. Venous interventions were used to treat reflux and varicosities. Patients’ characteristics, venous clinical severity scores (VCSS), EuroQol EQ-5D, and AVVQ-Thai were collected pre- and one-month post-intervention. AVVQ-Thai was also collected one to two weeks after the initial visit by reply-paid postal questionnaire. Results The study included 119 patients (30% C2, 29% C3, 28% C4, 11% C5, and 2% C6). The AVVQ-Thai had good internal consistency with Cronbach’s alpha of 0.783 and moderate reliability with the intraclass correlation coefficient of 0.67 (95%CI: 0.50, 0.79). The AVVQ-Thai was significantly correlated with VCSS and was able to discriminate patients with different levels of health problems as assessed by EQ-5D at both pre-and post-intervention, demonstrating good construct and discriminative validity. The median AVVQ scores improved significantly after intervention from 15.4 (IQR 8.3, 24.2) to 4.2 (IQR 1.3, 8.4) in C2-C3, and 18.9 (IQR 14.1, 25.5) to 7.3 (IQR 4.6, 16.3) in C4-C6. The MCID of the AVVQ was 6.21 on the 0-100 scale, which equates to the level of difference necessary to be clinically meaningful. Conclusions AVVQ-Thai has satisfactory evidence for internal consistency, reliability, validity, and responsiveness to change and is recommended for application in Thailand.
in F1000Research on 2024-05-17 10:00:15 UTC.
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Author(s): Wei Wang (汪巍) and Brian A. Camley
Cells that collide with each other repolarize away from contact, in a process called contact inhibition of locomotion (CIL), which is necessary for correct development of the embryo. CIL can occur even when cells make a micron-scale contact with a neighbor—much smaller than their size. How precisely…
[Phys. Rev. E 109, 054408] Published Fri May 17, 2024
in Physical Review E: Biological physics on 2024-05-17 10:00:00 UTC.
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Developmental Coordination Disorder (DCD) significantly impacts motor coordination and hand-eye coordination in children, affecting their daily activities and academic performance. This study aims to investigate the efficacy of Physical Rehabilitation utilizing the Sensory Stimulation and Developmental Vestibular (SSDV) protocol in improving motor coordination and hand-eye coordination in children diagnosed with DCD. Children diagnosed with DCD will be recruited and randomly allocated to either the intervention group receiving Physical Rehabilitation using the SSDV protocol or the control group receiving standard care. The intervention will involve a structured program incorporating sensory stimulation and developmental vestibular activities tailored to the individual needs of participants. Motor coordination and hand-eye coordination will be assessed using standardized measures such as the Movement Assessment Battery for Children (MABC) and the Beery-Buktenica Developmental Test of Visual-Motor Integration (Beery VMI). Assessments will be conducted at baseline, post-intervention, and follow-up time points. This randomized controlled trial seeks to evaluate the effectiveness of Physical Rehabilitation using the SSDV protocol in enhancing motor coordination and hand-eye coordination in children with DCD. By employing standardized measures, this study aims to provide objective insights into the impact of the intervention. Findings from this trial may contribute to the development of evidence-based interventions for children with DCD, potentially improving their motor skills and overall functioning in daily life and academic settings. Registration: CTRI/2024/03/064467
in F1000Research on 2024-05-17 09:58:44 UTC.
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Chemoprophylactic prevention of veterinary heartworm disease in companion animals, caused by the vector-borne nematode parasite Dirofilaria immitis, is a multi-billion-dollar global market. Experimental use of cats and dogs in preclinical heartworm drug testing is increasing due to evolving drug-resistance to frontline macrocyclic lactones and renewed investment in alternative preventative drug research. We and others recently published data demonstrating proof-of-concept of utilising lymphopenic severe-combined immunodeficient (SCID) or Recombination Activating Gene (RAG)2 deficient mice with additional knockout of the IL-2/7 receptor gamma chain (γc) as alternative preventative drug screening research models of dirofilariasis. Here we summarise the current knowledge of candidate immunodeficient mouse models tested, including a comparison of susceptibility using different background strains of mice, different D. immitis isolates, following use of anti-inflammatory treatments to further suppress residual innate immunity, and efficacies achieved against different reference anthelmintics. We supplement this precis with new data on treatment response to the veterinary anthelmintic, oxfendazole, and initial evaluation of D. immitis susceptibility in CB.17 SCID and C57BL/6 RAG2-/-γc-/- mice. We conclude that in addition to NSG and NXG mice, RAG2-/-γc-/- mice on either a BALB/c or C57BL/6 background offer an alternative screening model option, widening access to academic and commercial laboratories wishing to pursue initial rapid in vivo drug screening whilst avoiding potentially unnecessary cat or dog testing.
in F1000Research on 2024-05-17 09:56:35 UTC.
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Background Ophthalmologists deal with daily pseudoexfoliation (PXF) due to severe secondary glaucoma, which arises after cataract surgery. Cataracts with pseudoexfoliation are age-related and are associated with open-angle glaucoma. Therefore, pseudoexfoliation is expected to occur more frequently. Pseudoexfoliation is occasionally associated with the development of thick nuclear cataracts, which may make surgery challenging. risks of cataract extraction in patients with pseudoexfoliation include zonular weakness and inadequate pupillary dilation. This may cause vitreous loss, and intraoperative or postoperative lens displacement. It could also lead to a rise in postoperative intraocular pressure (IOP), progressing to long-term inflammation, phimosis of the capsular tissue, glaucoma, and surgical corneal decompensation. Recurrent secondary cataracts are typically caused by some remaining cortical tissue and decreased zonular support, which may lead to lens epithelial cell migration. Surgery for glaucoma and cataracts is complicated by the presence of pseudoexfoliative debris. Objectives To determine the prevalence of pseudoexfoliation in cataract patients visiting the ophthalmic OPD, AVBRH hospital, to locate patients with pseudoexfoliative cataracts, to evaluate their likelihood of progressing to open-angle glaucoma, and to examine the various ocular characteristics of these patients. Methodology The study participants will undergo ophthalmological examination after considering the inclusion and exclusion criteria. This examination will include sac syringing on the lacrimal gland, estimation of the highest corrected visual acuity, slit-lamp examination, application tonometer assessment of intraocular pressure (IOP), and fundus examination using an indirect ophthalmoscope. All individuals with cataracts visiting the ophthalmology department of AVBRH will be examined under a slit-lamp to determine the presence of pseudoexfoliation in the operating eye. Expected Results Hospital statistics from India indicated that the percentage of patients with pseudoexfoliation, in addition to cataracts, ranges from 1.87% to 13.5%.
in F1000Research on 2024-05-17 09:49:58 UTC.
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Abstract* Background Meningitis is an infection of leptomeninges. It is an emergency life-threatening condition that requires prompt treatment initiation. Diagnosis is the rate-limiting step because cerebrospinal fluid (CSF) analysis requires experienced personnel. Therefore, this study was conducted to assess the utility of urinary reagent strips for the rapid bedside diagnosis of CSF glucose, proteins, and leukocytes. Objective To determine the efficacy of a urinary reagent strip for bedside analysis of cerebrospinal fluid (CSF) samples. Methods This prospective comparative study will be conducted in the Department of Neonatology and Pediatrics, Jawaharlal Nehru Medical College, Sawangi, Wardha. CSF samples from patients suspected of infection of the central nervous system (CNS) and awaiting diagnosis will be subjected to semi-quantitative analysis using a urinary reagent strip (for glucose, proteins, and leukocytes). The results were compared with the laboratory results of the individual samples. Result After completing the study, we determined the efficacy of the urinary reagent strips in bedside estimation of CSF glucose, protein, and leukocyte levels in terms of sensitivity, specificity, positive and negative predictive values, and diagnostic accuracy. Conclusion This study provides insight into the utility of urinary reagent strips for rapid bedside diagnosis of CSF samples from patients suspected of having an infection.
in F1000Research on 2024-05-17 09:45:40 UTC.
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Protein-glutamine gamma-glutamyltransferase 2 (TGM2) is a Ca2+ dependent enzyme that catalyzes transglutaminase cross-linking modifications. TGM2 is involved in various diseases, either in a protective or contributory manner, making it a crucial protein to study and determine its therapeutic potential. Identifying high-performing TGM2 antibodies would facilitate these investigations. Here we have characterized seventeen TGM2 commercial antibodies for western blot and sixteen for immunoprecipitation, and immunofluorescence. The implemented standardized experimental protocol is based on comparing read-outs in knockout cell lines against their isogenic parental controls. This study is part of a larger, collaborative initiative seeking to address antibody reproducibility issues by characterizing commercially available antibodies for human proteins and publishing the results openly as a resource for the scientific community. While the use of antibodies and protocols vary between laboratories, we encourage readers to use this report as a guide to select the most appropriate antibodies for their specific needs.
in F1000Research on 2024-05-17 09:43:26 UTC.
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Background Centrifugal compressors are dynamic machines utilizing a rotating impeller, efficiently accelerate incoming gases, transforming kinetic energy into pressure energy for compression. They serve a wide range of industries, including air conditioning, refrigeration, gas turbines, industrial processes, and applications such as air compression, gas transportation, and petrochemicals, demonstrating their versatility. Designing a centrifugal compressor poses challenges related to achieving high aerodynamic efficiency, surge and choke control, material selection, rotor dynamics, cavitation, erosion, and addressing environmental considerations while balancing costs. Optimizing maintenance, reliability, and energy efficiency are essential aspects of the design process. Methods The primary objective of this research is to comprehensively investigate and improve the aerodynamic performance of centrifugal compressors. To accomplish this, a comprehensive investigation of variables such as blade number and hub diameter, along with various turbulence models will be conducted. This approach will leverage numerical techniques to fill the significant gaps in the current literature regarding centrifugal compressor design and optimization. The study encompasses the evaluation of two turbulence models, namely Shear Stress Transport and K-epsilon. Furthermore, it delves into the fine-tuning of blade geometry, including variations in blade number and hub diameter, aiming to refine the design for optimal performance. Extensive analyses using Ansys CFX encompass key variables such as Pressure, Mach Number, Density, Velocity, Turbulence Kinetic Energy, and Temperature. Results Notably, the optimized pressure profile yielded remarkable results, achieving a substantial 36% improvement, demonstrating the tangible benefits of these design enhancements. Conclusion The outcomes of this research hold significant utility for engineers, manufacturers, and regulatory bodies, offering invaluable insights and guidance to enhance compressor performance and efficiency.
in F1000Research on 2024-05-17 09:42:12 UTC.
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Objectives To investigate the impact of electroacupuncture on cognitive function, quality of life (QoL), and depression severity in patients with major depressive disorder (MDD). Methods This double-blinded randomized controlled trial included 60 participants aged 18-55 with cognitive symptoms related to MDD at Thammasat University Hospital. Participants were divided into two groups: the electroacupuncture group combined with standard antidepressant treatment (EG; n=30) and the control group receiving standard care with placebo acupuncture (CG; n=30). The study assessed 1) executive functions using the Trail making test- B and Stroop Color and Word Test, 2) delayed recall, and 3) subjective cognitive complaint and Quality of life (QoL) using WHODAS 2.0. Depressive symptoms were measured using the Thai version of the Patient Health Questionnaire (PHQ-9). Baseline and post-intervention assessments were conducted over 10 weeks. Mann-Whitney U test analyzed treatment effects by comparing median differences between groups. Results Both groups exhibited similar demographics and cognitive traits. Cognitive improvement was observed in both groups at the endpoint. Intention-to-treat analysis revealed significantly higher median scores for subjective cognitive complaints in the EG compared to the CG (EG: Median = 5.5, CG: Median = 0.0, p=0.049). No serious side effects were identified from either electroacupuncture or placebo acupuncture. Conclusions Electroacupuncture improved subjective complaints in MDD patients with cognitive symptoms, but did not show effects on specific cognitive functions, QoL, or depressive symptoms. This study provides initial evidence supporting the potential of electroacupuncture in MDD patients with cognitive symptoms, suggesting opportunities for further research. Trial registration NCT06239740, February 2, 2024, ClinicalTrials.gov.
in F1000Research on 2024-05-17 09:39:23 UTC.
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in Annals of Neurology on 2024-05-17 09:38:45 UTC.
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in Annals of Neurology on 2024-05-17 09:38:45 UTC.
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Stroke is the chief differential diagnosis in patient presenting to the emergency room with abrupt onset focal neurological deficits. Neuroimaging, including non-contrast computed tomography (CT), magnetic resonance imaging (MRI), vascular and perfusion imaging, is a cornerstone in the diagnosis and treatment decision-making. This review examines the current state of evidence behind the different imaging paradigms for acute ischemic stroke diagnosis and treatment, including current recommendations from the guidelines. Non-contrast CT brain, or in some centers MRI, can help differentiate ischemic stroke and intracerebral hemorrhage (ICH), a pivotal juncture in stroke diagnosis and treatment algorithm, especially for early window thrombolytics. Advanced imaging such as MRI or perfusion imaging can also assist making a diagnosis of ischemic stroke versus mimics such as migraine, Todd's paresis, or functional disorders. Identification of medium-large vessel occlusions with CT or MR angiography triggers consideration of endovascular thrombectomy (EVT), with additional perfusion imaging help identify salvageable brain tissue in patients who are likely to benefit from reperfusion therapies, particularly in the ≥6 h window. We also review recent advances in neuroimaging and ongoing trials in key therapeutic areas and their imaging selection criteria to inform the readers on potential future transitions into use of neuroimaging for stroke diagnosis and treatment decision making. ANN NEUROL 2024;95:1017–1034
in Annals of Neurology on 2024-05-17 09:38:45 UTC.
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Normothermic regional perfusion (NRP) has recently been used to augment organ donation after circulatory death (DCD) to improve the quantity and quality of transplantable organs. In DCD-NRP, after withdrawal of life-sustaining therapies and cardiopulmonary arrest, patients are cannulated onto extracorporeal membrane oxygenation to reestablish blood flow to targeted organs including the heart. During this process, aortic arch vessels are ligated to restrict cerebral blood flow. We review ethical challenges including whether the brain is sufficiently reperfused through collateral circulation to allow reemergence of consciousness or pain perception, whether resumption of cardiac activity nullifies the patient's prior death determination, and whether specific authorization for DCD-NRP is required. ANN NEUROL 2024;95:1035–1039
in Annals of Neurology on 2024-05-17 09:38:45 UTC.
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in Annals of Neurology on 2024-05-17 09:38:45 UTC.
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Eomesodermin-expressing (Eomes+) T-helper (Th) cells show cytotoxic characteristics in secondary progressive multiple sclerosis. We found that Eomes+ Th cell frequency was increased in the peripheral blood of amyotrophic lateral sclerosis and Alzheimer's disease patients. Furthermore, granzyme B production by Th cells from such patients was high compared with controls. A high frequency of Eomes+ Th cells was observed in the initial (acutely progressive) stage of amyotrophic lateral sclerosis, and a positive correlation between Eomes+ Th cell frequency and cognitive decline was observed in Alzheimer's disease patients. Therefore, Eomes+ Th cells may be involved in the pathology of amyotrophic lateral sclerosis and Alzheimer's disease. ANN NEUROL 2024;95:1093–1098
in Annals of Neurology on 2024-05-17 09:38:45 UTC.
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in Annals of Neurology on 2024-05-17 09:38:45 UTC.
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Pathogenic variants in PRKN cause early-onset Parkinson's disease (PD), while the role of alpha-synuclein in PRKN-PD remains uncertain. One study performed a blood-based alpha-synuclein seed amplification assay (SAA) in PRKN-PD, not detecting seed amplification in 17 PRKN-PD patients. By applying a methodologically different SAA focusing on neuron-derived extracellular vesicles, we demonstrated alpha-synuclein seed amplification in 8 of 13 PRKN-PD patients, challenging the view of PRKN-PD as a non-synucleinopathy. Moreover, we performed blinded replication of the neuron-derived extracellular vesicles-dependent SAA in idiopathic PD patients and healthy controls. In conclusion, blood-based neuron-derived extracellular vesicles-dependent SAA represents a promising biomarker to elucidate the underpinnings of (monogenic) PD. ANN NEUROL 2024;95:1173–1177
in Annals of Neurology on 2024-05-17 09:38:45 UTC.
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Objective
To apply a machine learning analysis to clinical and presynaptic dopaminergic imaging data of patients with rapid eye movement (REM) sleep behavior disorder (RBD) to predict the development of Parkinson disease (PD) and dementia with Lewy bodies (DLB).
Methods
In this multicenter study of the International RBD study group, 173 patients (mean age 70.5 ± 6.3 years, 70.5% males) with polysomnography-confirmed RBD who eventually phenoconverted to overt alpha-synucleinopathy (RBD due to synucleinopathy) were enrolled, and underwent baseline presynaptic dopaminergic imaging and clinical assessment, including motor, cognitive, olfaction, and constipation evaluation. For comparison, 232 RBD non-phenoconvertor patients (67.6 ± 7.1 years, 78.4% males) and 160 controls (68.2 ± 7.2 years, 53.1% males) were enrolled. Imaging and clinical features were analyzed by machine learning to determine predictors of phenoconversion.
Results
Machine learning analysis showed that clinical data alone poorly predicted phenoconversion. Presynaptic dopaminergic imaging significantly improved the prediction, especially in combination with clinical data, with 77% sensitivity and 85% specificity in differentiating RBD due to synucleinopathy from non phenoconverted RBD patients, and 85% sensitivity and 86% specificity in discriminating PD-converters from DLB-converters. Quantification of presynaptic dopaminergic imaging showed that an empirical z-score cutoff of −1.0 at the most affected hemisphere putamen characterized RBD due to synucleinopathy patients, while a cutoff of −1.0 at the most affected hemisphere putamen/caudate ratio characterized PD-converters.
Interpretation
Clinical data alone poorly predicted phenoconversion in RBD due to synucleinopathy patients. Conversely, presynaptic dopaminergic imaging allows a good prediction of forthcoming phenoconversion diagnosis. This finding may be used in designing future disease-modifying trials. ANN NEUROL 2024;95:1178–1192
in Annals of Neurology on 2024-05-17 09:38:45 UTC.
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Objective
The aim of this study was to investigate the cognitive effects of unilateral directional versus ring subthalamic nucleus deep brain stimulation (STN DBS) in patients with advanced Parkinson's disease.
Methods
We examined 31 participants who underwent unilateral STN DBS (left n = 17; right n = 14) as part of an National Institutes of Health (NIH)-sponsored randomized, double-blind, crossover study contrasting directional versus ring stimulation. All participants received unilateral DBS implants in the hemisphere more severely affected by motor parkinsonism. Measures of cognition included verbal fluency, auditory-verbal memory, and response inhibition. We used mixed linear models to contrast the effects of directional versus ring stimulation and implant hemisphere on longitudinal cognitive function.
Results
Crossover analyses showed no evidence for group-level changes in cognitive performance related to directional versus ring stimulation. Implant hemisphere, however, impacted cognition in several ways. Left STN participants had lower baseline verbal fluency than patients with right implants (t [20.66 = −2.50, p = 0.02]). Verbal fluency declined after left (p = 0.013) but increased after right STN DBS (p < 0.001), and response inhibition was faster following right STN DBS (p = 0.031). Regardless of hemisphere, delayed recall declined modestly over time versus baseline (p = 0.001), and immediate recall was unchanged.
Interpretation
Directional versus ring STN DBS did not differentially affect cognition. Similar to prior bilateral DBS studies, unilateral left stimulation worsened verbal fluency performance. In contrast, unilateral right STN surgery increased performance on verbal fluency and response inhibition tasks. Our findings raise the hypothesis that unilateral right STN DBS in selected patients with predominant right brain motor parkinsonism could mitigate declines in verbal fluency associated with the bilateral intervention. ANN NEUROL 2024;95:1205–1219
in Annals of Neurology on 2024-05-17 09:38:45 UTC.
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Objective
The aim of this study was to investigate whether, compared to pediatric healthy controls (HCs), the glymphatic system is impaired in pediatric multiple sclerosis (MS) patients according to their cognitive status, and to assess its association with clinical disability and MRI measures of brain structural damage.
Methods
Sixty-five pediatric MS patients (females = 62%; median age = 15.5 [interquartile range, IQR = 14.5;17.0] years) and 23 age- and sex-matched HCs (females = 44%; median age = 14.1 [IQR = 11.8;16.2] years) underwent neurological, neuropsychological and 3.0 Tesla MRI assessment, including conventional and diffusion tensor imaging (DTI). We calculated the diffusion along the perivascular space (DTI-ALPS) index, a proxy of glymphatic function. Cognitive impairment (Co-I) was defined as impairment in at least 2 cognitive domains.
Results
No significant differences in DTI-ALPS index were found between HCs and cognitively preserved (Co-P) pediatric MS patients (estimated mean difference [EMD] = −0.002 [95% confidence interval = −0.069; 0.065], FDR-p = 0.956). Compared to HCs and Co-P patients, Co-I pediatric MS patients (n = 20) showed significantly lower DTI-ALPS index (EMD = −0.136 [95% confidence interval = −0.214; −0.058], FDR-p ≤ 0.004). In HCs, no associations were observed between DTI-ALPS index and normalized brain, cortical and thalamic volumes, and normal-appearing white matter (NAWM) fractional anisotropy (FA) and mean diffusivity (MD) (FDR-p ≥ 0.348). In pediatric MS patients, higher brain WM lesion volume (LV), higher NAWM MD, lower normalized thalamic volume, and lower NAWM FA were associated with lower DTI-ALPS index (FDR-p ≤ 0.016). Random Forest selected lower DTI-ALPS index (relative importance [RI] = 100%), higher brain WM LV (RI = 59.5%) NAWM MD (RI = 57.1%) and intelligence quotient (RI = 51.3%) as informative predictors of cognitive impairment (out-of-bag area under the curve = 0.762).
Interpretation
Glymphatic system dysfunction occurs in pediatric MS, is associated with brain focal lesions, irreversible tissue loss accumulation and cognitive impairment. ANN NEUROL 2024;95:1080–1092
in Annals of Neurology on 2024-05-17 09:38:45 UTC.
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Objective
Along with the known effects of stress on brain structure and inflammatory processes, increasing evidence suggest a role of chronic stress in the pathogenesis of Alzheimer's disease (AD). We investigated the association of accumulated stressful life events (SLEs) with AD pathologies, neuroinflammation, and gray matter (GM) volume among cognitively unimpaired (CU) individuals at heightened risk of AD.
Methods
This cross-sectional cohort study included 1,290 CU participants (aged 48–77) from the ALFA cohort with SLE, lumbar puncture (n = 393), and/or structural magnetic resonance imaging (n = 1,234) assessments. Using multiple regression analyses, we examined the associations of total SLEs with cerebrospinal fluid (1) phosphorylated (p)-tau181 and Aβ1–42/1–40 ratio, (2) interleukin 6 (IL-6), and (3) GM volumes voxel-wise. Further, we performed stratified and interaction analyses with sex, history of psychiatric disease, and evaluated SLEs during specific life periods.
Results
Within the whole sample, only childhood and midlife SLEs, but not total SLEs, were associated with AD pathophysiology and neuroinflammation. Among those with a history of psychiatric disease SLEs were associated with higher p-tau181 and IL-6. Participants with history of psychiatric disease and men, showed lower Aβ1–42/1–40 with higher SLEs. Participants with history of psychiatric disease and women showed reduced GM volumes in somatic regions and prefrontal and limbic regions, respectively.
Interpretation
We did not find evidence supporting the association of total SLEs with AD, neuroinflammation, and atrophy pathways. Instead, the associations appear to be contingent on events occurring during early and midlife, sex and history of psychiatric disease. ANN NEUROL 2024;95:1058–1068
in Annals of Neurology on 2024-05-17 09:38:45 UTC.
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Objective
In the era of stereoelectroencephalography (SEEG), many studies have been devoted to understanding the role of interictal high-frequency oscillations. High-frequency activity (HFA) at seizure onset has been identified as a marker of epileptogenic zone. We address the physiological significance of ictal HFAs and their relation to clinical semiology.
Methods
We retrospectively identified patients with pure focal primary motor epilepsy. We selected only patients in whom SEEG electrodes were optimally placed in the motor cortex as confirmed by electrical stimulation. Based on these narrow inclusion criteria, we extensively studied 5 patients (3 males and 2 females, mean age = 22.4 years) using time–frequency analysis and time correlation with motor signs onset.
Results
A total of 157 analyzable seizures were recorded in 5 subjects. The first 2 subjects had tonic or clonic semiology with rare secondary generalization. Subject 3 had atonic onset followed by clonic hand/arm flexion. Subject 4 had clusters of tonic and atonic facial movements. Subject 5 had upper extremity tonic movements. The median frequency of the fast activity extracted from the Epileptogenic Zone Fingerprint pipeline in the first 4 subjects was 76 Hz (interquartile range = 21.9Hz). Positive motor signs did not occur concomitantly with high gamma activity developing in the motor cortex. Motor signs began at the end of HFAs.
Interpretation
This study supports the hypothesis of an inhibitory effect of ictal HFAs. The frequency range in the gamma band was associated with the direction of the clinical output effect. Changes from inhibitory to excitatory effect occurred when discharge frequency dropped to low gamma or beta. ANN NEUROL 2024;95:1127–1137
in Annals of Neurology on 2024-05-17 09:38:45 UTC.
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Objective
People who eat healthier diets are less likely to develop dementia, but the biological mechanism of this protection is not well understood. We tested the hypothesis that healthy diet protects against dementia because it slows the pace of biological aging.
Methods
We analyzed Framingham Offspring Cohort data. We included participants ≥60 years-old, free of dementia and having dietary, epigenetic, and follow-up data. We assessed healthy diet as long-term adherence to the Mediterranean-Dash Intervention for Neurodegenerative Delay diet (MIND, over 4 visits spanning 1991–2008). We measured the pace of aging from blood DNA methylation data collected in 2005–2008 using the DunedinPACE epigenetic clock. Incident dementia and mortality were defined using study records compiled from 2005 to 2008 visit through 2018.
Results
Of n = 1,644 included participants (mean age 69.6, 54% female), n = 140 developed dementia and n = 471 died over 14 years of follow-up. Greater MIND score was associated with slower DunedinPACE and reduced risks for dementia and mortality. Slower DunedinPACE was associated with reduced risks for dementia and mortality. In mediation analysis, slower DunedinPACE accounted for 27% of the diet-dementia association and 57% of the diet-mortality association.
Interpretation
Findings suggest that slower pace of aging mediates part of the relationship of healthy diet with reduced dementia risk. Monitoring pace of aging may inform dementia prevention. However, a large fraction of the diet-dementia association remains unexplained and may reflect direct connections between diet and brain aging that do not overlap other organ systems. Investigation of brain-specific mechanisms in well-designed mediation studies is warranted. ANN NEUROL 2024;95:1069–1079
in Annals of Neurology on 2024-05-17 09:38:45 UTC.
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Objective
Androgens have been hypothesized to be involved in the pathophysiology of cluster headache due to the male predominance, but whether androgens are altered in patients with cluster headache remains unclear.
Methods
We performed a prospective, case-controlled study in adult males with cluster headache. Sera were measured for hormones including testosterone, luteinizing hormone (LH), and sex hormone-binding globulin in 60 participants with episodic cluster headache (during a bout and in remission), 60 participants with chronic cluster headache, and 60 age- and sex-matched healthy controls. Free testosterone (fT) was calculated according to the Vermeulen equation. Shared genetic risk variants were assessed between cluster headache and testosterone concentrations.
Results
The mean fT/LH ratio was reduced by 35% (95% confidence interval [CI]: 21%–47%, p < 0.0001) in patients with chronic cluster headache and by 24% (95% CI: 9%–37%, p = 0.004) in patients with episodic cluster headache compared to controls after adjusting for age, sleep duration, and use of acute medication. Androgen concentrations did not differ between bouts and remissions. Furthermore, a shared genetic risk allele, rs112572874 (located in the intron of the microtubule associated protein tau (MAPT) gene on chromosome 17), between fT and cluster headache was identified.
Interpretation
Our results demonstrate that the male endocrine system is altered in patients with cluster headache to a state of compensated hypogonadism, and this is not an epiphenomenon associated with sleep or the use of acute medication. Together with the identified shared genetic risk allele, this may suggest a pathophysiological link between cluster headache and fT. ANN NEUROL 2024;95:1149–1161
in Annals of Neurology on 2024-05-17 09:38:45 UTC.
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Objective
Although off-label use of rituximab is a common alternative to disease-modifying therapies (DMTs) approved for multiple sclerosis (MS) in several countries, the impact of this on treatment cost-effectiveness is not well known.
Methods
We evaluated the relative cost-effectiveness of rituximab and MS-approved DMTs in a register-based cohort study of Swedish residents with relapsing–remitting MS, aged 18–65 years, starting treatment with rituximab, natalizumab, fingolimod, or dimethyl fumarate between January 2010 and July 2016, and followed through July 2021 (n = 5,924). By linking the population-based Swedish MS register to several Swedish health care and demographic registers, we estimated health care costs in relation to number of relapses, over 5 years from treatment start. Differences between treatments were estimated in inverse probability of treatment-weighted regression models, adjusting for a broad range of potential confounders covering demographics, medical history, and MS-related clinical characteristics.
Results
Off-label rituximab was associated with both lower total health care costs (mean cost savings ranged $35,000–$66,000 vs. each approved DMT), and fewer relapses (mean number of prevented relapses ranged 0.12–0.22), per started therapy over 5 years. Results were robust to variations in discounting and pricing of health care visits, with the main driver of cost-savings being the price of the index drug itself.
Interpretation
The cost-effectiveness of rituximab dominated the MS-approved alternatives. Off-label, low-dose rituximab should be considered for persons with MS and could reduce barriers to treatment, especially in resource-limited settings. ANN NEUROL 2024;95:1099–1111
in Annals of Neurology on 2024-05-17 09:38:45 UTC.
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Objectives
Intracerebral hemorrhage (ICH) and cerebral microbleeds (CMB) in cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy are more common in East Asian populations than in people of white European ancestry. We hypothesized that the ethnic difference is explained by the East Asian-specific NOTCH3 p.R75P mutation.
Methods
This retrospective observational study included 118 patients with cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy in Japanese and Korean cohorts. We investigated whether the p.R75P mutation is associated with symptomatic ICH and multiple CMB (>5) using quasi-Poisson regression models. We predicted the NOTCH3 extracellular domain protein structures in silico and graded NOTCH3 extracellular domain immunostaining in skin vessels of some patients, with subsequent comparisons between p.R75P and other conventional mutations.
Results
Among 63 Japanese patients (median age 55 years; 56% men), 15 had a p.R75P mutation, significantly associated with symptomatic ICH (adjusted relative risk 9.56, 95% CI 2.45–37.31), multiple CMB (3.00, 1.34–6.71), and absence of temporopolar lesions (4.91, 2.29–10.52) after adjustment for age, sex, hypertension, and antithrombotics. In the Korean cohort (n = 55; median age 55 years; 51% men), the p.R75P mutation (n = 13) was also associated with symptomatic ICH (8.11, 1.83–35.89), multiple CMB (1.90, 1.01–3.56), and absence of temporopolar lesions (2.32, 1.08–4.97). Structural analysis revealed solvent-exposed free cysteine thiols in conventional mutations, directly causing aggregation, whereas a stereochemically incompatible proline residue structure in p.R75P lowers correct disulfide bond formation probability, indirectly causing aggregation. Pathologically, the p.R75P mutation resulted in less vascular NOTCH3 extracellular domain accumulation than the other conventional mutations.
Interpretation
NOTCH3 p.R75P mutation is associated with hemorrhagic presentations, milder temporopolar lesions, and distinct mutant protein structure properties. ANN NEUROL 2024;95:1040–1054
in Annals of Neurology on 2024-05-17 09:38:45 UTC.
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Neidhart et al. report that intrathecal production of IgG antibodies against measles-, rubella- and/or varicella zoster virus, called “MRZ reaction”, is highly specific for multiple sclerosis and associated with the human leukocyte antigen HLA-DR15 and female sex. These findings indicate that T-B cell interactions via HLA class II molecules and sex hormones and/or X chromosome-encoded factors shape intrathecal antiviral antibody production in MS patients with MRZ reaction.
Objective
Specific human leucocyte antigen (HLA) alleles are not only associated with higher risk to develop multiple sclerosis (MS) and other autoimmune diseases, but also with the severity of various viral and bacterial infections. Here, we analyzed the most specific biomarker for MS, that is, the polyspecific intrathecal IgG antibody production against measles, rubella, and varicella zoster virus (MRZ reaction), for possible HLA associations in MS.
Methods
We assessed MRZ reaction from 184 Swiss patients with MS and clinically isolated syndrome (CIS) and 89 Swiss non-MS/non-CIS control patients, and performed HLA sequence-based typing, to check for associations of positive MRZ reaction with the most prevalent HLA alleles. We used a cohort of 176 Swedish MS/CIS patients to replicate significant findings.
Results
Whereas positive MRZ reaction showed a prevalence of 38.0% in MS/CIS patients, it was highly specific (97.7%) for MS/CIS. We identified HLA-DRB1*15:01 and other tightly linked alleles of the HLA-DR15 haplotype as the strongest HLA-encoded risk factors for a positive MRZ reaction in Swiss MS/CIS (odds ratio [OR], 3.90, 95% confidence interval [CI] 2.05–7.46, p
adjusted = 0.0004) and replicated these findings in Swedish MS/CIS patients (OR 2.18, 95%-CI 1.16–4.02, p
adjusted = 0.028). In addition, female MS/CIS patients had a significantly higher probability for a positive MRZ reaction than male patients in both cohorts combined (p
adjusted <0.005).
Interpretation
HLA-DRB1*15:01, the strongest genetic risk factor for MS, and female sex, 1 of the most prominent demographic risk factors for developing MS, predispose in MS/CIS patients for a positive MRZ reaction, the most specific CSF biomarker for MS. ANN NEUROL 2024;95:1112–1126
in Annals of Neurology on 2024-05-17 09:38:45 UTC.
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Objective
The objective was to analyze seizure semiology in pediatric frontal lobe epilepsy patients, considering age, to localize the seizure onset zone for surgical resection in focal epilepsy.
Methods
Fifty patients were identified retrospectively, who achieved seizure freedom after frontal lobe resective surgery at Great Ormond Street Hospital. Video-electroencephalography recordings of preoperative ictal seizure semiology were analyzed, stratifying the data based on resection region (mesial or lateral frontal lobe) and age at surgery (≤4 vs >4).
Results
Pediatric frontal lobe epilepsy is characterized by frequent, short, complex seizures, similar to adult cohorts. Children with mesial onset had higher occurrence of head deviation (either direction: 55.6% vs 17.4%; p = 0.02) and contralateral head deviation (22.2% vs 0.0%; p = 0.03), ictal body-turning (55.6% vs 13.0%; p = 0.006; ipsilateral: 55.6% vs 4.3%; p = 0.0003), and complex motor signs (88.9% vs 56.5%; p = 0.037). Both age groups (≤4 and >4 years) showed hyperkinetic features (21.1% vs 32.1%), contrary to previous reports. The very young group showed more myoclonic (36.8% vs 3.6%; p = 0.005) and hypomotor features (31.6% vs 0.0%; p = 0.003), and fewer behavioral features (36.8% vs 71.4%; p = 0.03) and reduced responsiveness (31.6% vs 78.6%; p = 0.002).
Interpretation
This study presents the most extensive semiological analysis of children with confirmed frontal lobe epilepsy. It identifies semiological features that aid in differentiating between mesial and lateral onset. Despite age-dependent differences, typical frontal lobe features, including hyperkinetic seizures, are observed even in very young children. A better understanding of pediatric seizure semiology may enhance the accuracy of onset identification, and enable earlier presurgical evaluation, improving postsurgical outcomes. ANN NEUROL 2024;95:1138–1148
in Annals of Neurology on 2024-05-17 09:38:45 UTC.
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Objective
To characterize DNA methylation (DNAm) differences between sporadic Parkinson's disease (PD) and healthy control (HC) individuals enrolled in the Parkinson's Progression Markers Initiative (PPMI).
Methods
Using whole blood, we characterized longitudinal differences in DNAm between sporadic PD patients (n = 196) and HCs (n = 86) enrolled in PPMI. RNA sequencing (RNAseq) was used to conduct gene expression analyses for genes mapped to differentially methylated cytosine-guanine sites (CpGs).
Results
At the time of patient enrollment, 5,178 CpGs were differentially methylated (2,683 hypermethylated and 2,495 hypomethylated) in PD compared to HC. Of these, 579 CpGs underwent significant methylation changes over 3 years. Several differentially methylated CpGs were found near the cytochrome P450 family 2 subfamily E member 1 (CYP2E1) gene. Additionally, multiple hypermethylated CpGs were associated with the N-myc downregulated gene family member 4 (NDRG4) gene. RNA-Seq analyses showed 75 differentially expressed genes in PD patients compared to controls. An integrative analysis of both differentially methylated sites and differentially expressed genes revealed 20 genes that exhibited hypomethylation concomitant with overexpression. Additionally, 1 gene, cathepsin H (CTSH), displayed hypermethylation that was associated with its decreased expression.
Interpretation
We provide initial evidence of alterations in DNAm in blood of PD patients that may serve as potential epigenetic biomarker of disease. To evaluate the significance of these changes throughout the progression of PD, additional profiling at longer intervals and during the prodromal stages of disease will be necessary. ANN NEUROL 2024;95:1162–1172
in Annals of Neurology on 2024-05-17 09:38:45 UTC.
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Objective
Despite recent attention to cognitive impairment in essential tremor, few studies examine rates of conversion to diagnoses of mild cognitive impairment and dementia. Development of dementia in essential tremor is associated with loss of functional ability and a doubling of mortality rate. This prospective, longitudinal study comprehensively reports the prevalence and incidence of, and the annual rates of conversion to, mild cognitive impairment and dementia in an essential tremor cohort.
Methods
Patients underwent detailed cognitive assessments and were assigned diagnoses of normal cognition, mild cognitive impairment, or dementia. There were 222 patients at baseline (mean age = 79.3 ± 9.7 years), and 177 patients participated in follow-up evaluations at 18, 36, 54, and 72 months (mean years of observation = 5.1 ± 1.7). Data were compared to those of historical controls and Parkinson disease patients.
Results
The cumulative prevalence of dementia and average annual conversion rate of mild cognitive impairment to dementia were 18.5% and 12.2%, nearly three times higher than rates in the general population, and approximately one half the magnitude of those reported for Parkinson disease patients. The cumulative prevalence of mild cognitive impairment (26.6%) was almost double that of the general population, but less than that in Parkinson disease populations.
Interpretation
We present the most complete exposition of the longitudinal trajectory of cognitive impairment in an essential tremor cohort yet presented. The prevalence of and conversion rates to dementia in essential tremor fall between those associated with the natural course of aging and the more pronounced rates observed in Parkinson disease. ANN NEUROL 2024;95:1193–1204
in Annals of Neurology on 2024-05-17 09:38:45 UTC.
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Background Partner violence is a significant issue affecting women’s health, particularly their breastfeeding practices in healthcare settings. Despite a considerable body of research on this topic, there is a need for a systematic overview of the existing literature to explore its thematic and structural developments. Methods This scientometric analysis covers a period of 45 years (1977-2022) and identifies 415 peer-reviewed articles published in English before 2023 from the Scopus database. The articles were included if they engaged with themes related to partner violence, healthcare settings, breastfeeding, and mothers, using predefined search terms and filters. Bibliometric data were decoded and visualized using VOSviewer and RStudio to analyze and visualize the scientific dialogue, trends, patterns, and networks in the literature regarding partner violence and its impact on breastfeeding mothers in healthcare settings. Results The study revealed a concentrated exploration of themes related to violence, healthcare provision, mental health, and women’s reproductive health. The co-occurrence network and thematic mapping illuminated seven pivotal clusters, revealing a complex narrative of interconnected research areas. Niche and emerging themes such as “Depression,” “HIV,” and “Covid-19” were identified, highlighting the evolving landscape of the research domain. Conclusions This analysis provides a panoramic overview of the existing literature, revealing intricate thematic structures and collaboration networks within the research on partner violence and breastfeeding mothers in healthcare settings. The study not only sheds light on the historical and current states of research but also pinpoints potential future directions, thereby assisting scholars and policymakers in navigating and prioritizing subsequent investigative endeavors.
in F1000Research on 2024-05-17 09:37:05 UTC.
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in Hippocampus on 2024-05-17 09:36:03 UTC.
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Abstract
Evidence suggests that individual hippocampal subfields are preferentially involved in various memory-related processes. Here, we demonstrated dissociations in these memory processes in two unique individuals with near-selective bilateral damage within the hippocampus, affecting the dentate gyrus (DG) in case BL and the cornu ammonis 1 (CA1) subfield in case BR. BL was impaired in discriminating highly similar objects in memory (i.e., mnemonic discrimination) but exhibited preserved overall recognition of studied objects, regardless of similarity. Conversely, BR demonstrated impaired general recognition. These results provide evidence for the DG in discrimination processes, likely related to underlying pattern separation computations, and the CA1 in retention/retrieval.
in Hippocampus on 2024-05-17 09:36:03 UTC.
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Abstract
Researchers who study the human hippocampus are naturally interested in how its subfields function. However, many researchers are precluded from examining subfields because their manual delineation from magnetic resonance imaging (MRI) scans (still the gold standard approach) is time consuming and requires significant expertise. To help ameliorate this issue, we present here two protocols, one for 3T MRI and the other for 7T MRI, that permit automated hippocampus segmentation into six subregions, namely dentate gyrus/cornu ammonis (CA)4, CA2/3, CA1, subiculum, pre/parasubiculum, and uncus along the entire length of the hippocampus. These protocols are particularly notable relative to existing resources in that they were trained and tested using large numbers of healthy young adults (n = 140 at 3T, n = 40 at 7T) whose hippocampi were manually segmented by experts from MRI scans. Using inter-rater reliability analyses, we showed that the quality of automated segmentations produced by these protocols was high and comparable to expert manual segmenters. We provide full open access to the automated protocols, and anticipate they will save hippocampus researchers a significant amount of time. They could also help to catalyze subfield research, which is essential for gaining a full understanding of how the hippocampus functions.
in Hippocampus on 2024-05-17 09:36:03 UTC.
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Abstract
Our ability to navigate in a new environment depends on learning new locations. Mental representations of locations are quickly accessible during navigation and allow us to know where we are regardless of our current viewpoint. Recent functional magnetic resonance imaging (fMRI) research using pattern classification has shown that these location-based representations emerge in the retrosplenial cortex and parahippocampal gyrus, regions theorized to be critically involved in spatial navigation. However, little is currently known about the oscillatory dynamics that support the formation of location-based representations. We used magnetoencephalogram (MEG) recordings to investigate region-specific oscillatory activity in a task where participants could form location-based representations. Participants viewed videos showing that two perceptually distinct scenes (180° apart) belonged to the same location. This “overlap” video allowed participants to bind the two distinct scenes together into a more coherent location-based representation. Participants also viewed control “non-overlap” videos where two distinct scenes from two different locations were shown, where no location-based representation could be formed. In a post-video behavioral task, participants successfully matched the two viewpoints shown in the overlap videos, but not the non-overlap videos, indicating they successfully learned the locations in the overlap condition. Comparing oscillatory activity between the overlap and non-overlap videos, we found greater theta and alpha/beta power during the overlap relative to non-overlap videos, specifically at time-points when we expected scene integration to occur. These oscillations localized to regions in the medial parietal cortex (precuneus and retrosplenial cortex) and the medial temporal lobe, including the hippocampus. Therefore, we find that theta and alpha/beta oscillations in the hippocampus and medial parietal cortex are likely involved in the formation of location-based representations.
in Hippocampus on 2024-05-17 09:36:03 UTC.
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in Annals of Neurology on 2024-05-17 09:05:51 UTC.
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in Annals of Neurology on 2024-05-17 08:59:34 UTC.
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Objective
This study was undertaken to delineate 21-year sex-specific trends in recurrence and postrecurrence mortality.
Methods
Between 2000 and 2020, first-ever ischemic stroke (IS) patients, ascertained from the population-based BASIC (Brain Attack Surveillance in Corpus Christi) project in South Texas, were followed for recurrent stroke and all-cause mortality until December 31, 2020. Multivariable regression models with an interaction between calendar year and sex were used to estimate sex-specific trends and sex differences in recurrence and postrecurrence mortality.
Results
Of the 6,057 IS patients (median age = 69 years, 49.8% women), 654 (10.8%) had a recurrence and 399 (47.7%) had postrecurrence mortality during 5 years of follow-up. In 2000, women had 2.5% higher albeit non-statistically significant 5-year risk of recurrence than men in absolute scale. With the trend declining in women by 7.6% (95% confidence interval [CI] = −10.8 to −4.5%) and in men by 3.6% (95% CI = −6.5% to −0.7%), the risk at the end of the study period was 1.5% (95% CI = −0.3% to 3.6%) lower among women than men. For postrecurrence mortality, the risk was 10.2% lower among women in 2000, but the sex difference was 3.3% by the end of the period, which was due to a larger overall increase in the risk among women than men over the entire time period.
Interpretation
The declines in recurrent stroke suggest successful secondary stroke prevention, especially in women. However, the continued high postrecurrence mortality among both sexes at the end of study period emphasizes the need for ongoing interventions to improve prognosis in those who have had recurrent cerebrovascular events. ANN NEUROL 2024
in Annals of Neurology on 2024-05-17 07:35:06 UTC.
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Science, Volume 384, Issue 6697, May 2024.
in Science on 2024-05-17 07:00:00 UTC.
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Science, Volume 384, Issue 6697, May 2024.
in Science on 2024-05-17 07:00:00 UTC.
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Science, Volume 384, Issue 6697, May 2024.
in Science on 2024-05-17 07:00:00 UTC.
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Science, Volume 384, Issue 6697, May 2024.
in Science on 2024-05-17 07:00:00 UTC.
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Science Advances, Volume 10, Issue 20, May 2024.
in Science Advances on 2024-05-17 07:00:00 UTC.
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Science Advances, Volume 10, Issue 20, May 2024.
in Science Advances on 2024-05-17 07:00:00 UTC.
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Science Advances, Volume 10, Issue 20, May 2024.
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Science Advances, Volume 10, Issue 20, May 2024.
in Science Advances on 2024-05-17 07:00:00 UTC.
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Science Advances, Volume 10, Issue 20, May 2024.
in Science Advances on 2024-05-17 07:00:00 UTC.
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Science Advances, Volume 10, Issue 20, May 2024.
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Science Advances, Volume 10, Issue 20, May 2024.
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Science Advances, Volume 10, Issue 20, May 2024.
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Science Advances, Volume 10, Issue 20, May 2024.
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Science Advances, Volume 10, Issue 20, May 2024.
in Science Advances on 2024-05-17 07:00:00 UTC.
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Science Advances, Volume 10, Issue 20, May 2024.
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Science Advances, Volume 10, Issue 20, May 2024.
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Science Advances, Volume 10, Issue 20, May 2024.
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Science Advances, Volume 10, Issue 20, May 2024.
in Science Advances on 2024-05-17 07:00:00 UTC.
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Science Advances, Volume 10, Issue 20, May 2024.
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Science Advances, Volume 10, Issue 20, May 2024.
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Science Advances, Volume 10, Issue 20, May 2024.
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Science Advances, Volume 10, Issue 20, May 2024.
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Science Advances, Volume 10, Issue 20, May 2024.
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Science Advances, Volume 10, Issue 20, May 2024.
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Science Advances, Volume 10, Issue 20, May 2024.
in Science Advances on 2024-05-17 07:00:00 UTC.
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Science Advances, Volume 10, Issue 20, May 2024.
in Science Advances on 2024-05-17 07:00:00 UTC.
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Members of both the Piezo and transmembrane channel-like (TMC) families are bona fide mammalian mechanotransducers. In a recent study, Zhang, Shao et al. discovered that TMC7, a non-mechanosensitive TMC, inhibits Piezo2-dependent mechanosensation, with implications for the importance of cellular context for Piezo2 channels in normal and pathological responses to mechanical pain.
in Trends in Neurosciences: In press on 2024-05-17 00:00:00 UTC.
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Evidence of central nervous system (CNS) exogenous opioid effects in humans has been primarily gained through neuroimaging of three participant populations: individuals after acute opioid administration, those with opioid use disorder (OUD), and those with chronic pain receiving opioid therapy. In both the brain and spinal cord, opioids alter processes of pain, cognition, and reward. Opioid-related CNS effects may persist and accumulate with longer opioid use duration. Meanwhile, opioid-induced benefits versus risks to brain health remain unclear. This review article highlights recent accumulating evidence for how exogenous opioids impact the CNS in humans. While investigation of CNS opioid effects has remained largely disparate across contexts of opioid acute administration, OUD, and chronic pain opioid therapy, integration across these contexts may enable advancement toward effective interventions.
in Trends in Neurosciences: In press on 2024-05-17 00:00:00 UTC.
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Belur et al. identify a novel class of pathological inclusions comprising RNA binding proteins, NONO and SFPQ, and A-to-I-edited RNAs in neuronal nuclei of Parkinson’s disease and dementia with Lewy bodies. A-to-I-edited RNAs promote protein aggregation, inducing neurotoxicity by nuclear sequestration of essential transcripts encoding axon, synaptic, and mitochondrial proteins.
in Neuron: In press on 2024-05-17 00:00:00 UTC.
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Sensory deprivation reshapes developing neural circuits, and sensory feedback adjusts the strength of reflexive behaviors throughout life. Sensory development might therefore limit the rate with which behaviors mature, but the complexity of most sensorimotor circuits preclude identifying this fundamental constraint. Here we compared the functional development of components of the vertebrate vestibulo-ocular reflex circuit that stabilizes gaze. We found that vestibular interneuron responses to body tilt sensation developed well before behavioral performance peaked, even without motor neuron-derived feedback. Motor neuron responses developed similarly. Instead, the ontogeny of behavior matched the rate of neuromuscular junction development. When sensation was delayed until after the neuromuscular junction developed, behavioral performance was immediately strong. The matching timecourse and ability to determine behavior establish the development of the neuromuscular junction, and not sensory-derived information, as the rate-limiting process for an ancient and evolutionarily-conserved neural circuit.
in bioRxiv: Neuroscience on 2024-05-17 00:00:00 UTC.
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Biological sex shapes the manifestation and progression of neurodevelopmental disorders (NDDs). These disorders often demonstrate male-specific vulnerabilities; however, the identification of underlying mechanisms remains a significant challenge in the field. Hemideletion of the 16p11.2 region (16p11.2 del/+) is associated with NDDs, and mice modeling 16p11.2 del/+ exhibit sex-specific striatum-related phenotypes relevant to NDDs. Striatal circuits, crucial for locomotor control, consist of two distinct pathways: the direct and indirect pathways originating from D1 dopamine receptor (D1R) and D2 dopamine receptor (D2R) expressing spiny projection neurons (SPNs), respectively. In this study, we define the impact of 16p11.2 del/+ on striatal circuits in male and female mice. Using snRNA-seq, we identify sex- and cell type-specific transcriptomic changes in the D1- and D2-SPNs of 16p11.2 del/+ mice, indicating distinct transcriptomic signatures in D1-SPNs and D2-SPNs in males and females, with a ~5-fold greater impact in males. Further pathway analysis reveals differential gene expression changes in 16p11.2 del/+ male mice linked to synaptic plasticity in D1- and D2-SPNs and GABA signaling pathway changes in D1-SPNs. Consistent with our snRNA-seq study revealing changes in GABA signaling pathways, we observe distinct changes in miniature inhibitory postsynaptic currents (mIPSCs) in D1- and D2-SPNs from 16p11.2 del/+ male mice. Behaviorally, we utilize conditional genetic approaches to introduce the hemideletion selectively in either D1- or D2-SPNs and find that conditional hemideletion of genes in the 16p11.2 region in D2-SPNs causes hyperactivity in male mice, but hemideletion in D1-SPNs does not. Within the striatum, hemideletion of genes in D2-SPNs in the dorsal lateral striatum leads to hyperactivity in males, demonstrating the importance of this striatal region. Interestingly, conditional 16p11.2 del/+ within the cortex drives hyperactivity in both sexes. Our work reveals that a locus linked to NDDs acts in different striatal circuits, selectively impacting behavior in a sex- and cell type-specific manner, providing new insight into male vulnerability for NDDs.
in bioRxiv: Neuroscience on 2024-05-17 00:00:00 UTC.
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Introduction: Evoked compound action potentials (ECAPs) measured using epidural spinal recordings (ESRs) during epidural spinal cord stimulation (SCS) can help elucidate fundamental mechanisms for the treatment of pain, as well as inform closed-loop control of SCS. Previous studies have used ECAPs to characterize the neural response to various neuromodulation therapies and have demonstrated that ECAPs are highly prone to multiple sources of artifact, including post-stimulus pulse capacitive artifact, electromyography (EMG) bleed-through, and motion artifact resulting from disturbance of the electrode/tissue interface during normal behavior. However, a thorough characterization has yet to be performed for how these sources of artifact may contaminate recordings within the temporal window commonly used to determine activation of A-beta fibers in a large animal model. Methods: We characterized the sources of artifacts that can contaminate the recording of ECAPs in an epidural SCS swine model using the Abbott Octrode lead. Muscle paralytics were administered to block muscle activation preventing EMG from contaminating the recorded ECAPs. Concurrent EMG recordings of the longissimus, a long muscle of the back, were used to confirm a 2-4 millisecond (ms) latency source of EMG bleed-through that frequently contaminated the A-beta temporal window. Additionally, we obtained recordings approximately 5-10 minutes post-mortem after clear evoked A-beta and associated EMG responses ceased to characterize the representation of stimulation artifact across the array. Results: Spinal ECAP recordings can be contaminated by capacitive artifact, short latency EMG from nearby long muscles of the back, and motion artifact from multiple sources. In many cases, the capacitive artifact can appear nearly identical in duration and waveshape to evoked A-beta responses. These sources of EMG can have phase shifts across the electrode array, very similar to the phase shift anticipated by propagation of an evoked A-beta fiber response across the array. This short latency EMG is often evident at currents similar to those needed to activate A-beta fibers associated with the treatment of pain. Changes in cerebrospinal fluid between the cord and dura, and motion induced during breathing created a cyclic oscillation in all evoked components of the recorded ECAP signal. Conclusion: Careful controls must be implemented to accurately separate neural signal from the sources of artifact in spinal cord ECAPs. To address this, we suggest experimental procedures and associated reporting requirements necessary to disambiguate the underlying neural response from these confounds. These data are important to better understand the conceptual framework for recorded ESRs, with components such as ECAPs, EMG responses and artifacts, and have important implications for closed-loop control algorithms to account for transient motion such as postural changes and cough.
in bioRxiv: Neuroscience on 2024-05-17 00:00:00 UTC.
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Inhibitory control is a critical executive function that allows animals to suppress their impulsive behavior in order to achieve certain goals or avoid punishment. We investigated norepinephrine (NE) and acetylcholine (ACh) dynamics and population neuronal activity in the prefrontal cortex during inhibitory control. Using fluorescent sensors to measure extracellular levels of NE and ACh, we simultaneously recorded the dynamics of prefrontal NE and ACh in mice performing an inhibitory control task. The prefrontal NE and ACh signals exhibited strong coherence at 0.4-0.8 Hz. Chemogenetic inhibition of locus coeruleus (LC) neurons that project to the basal forebrain region reduced inhibitory control performance to chance levels. However, this manipulation did not diminish the difference in NE/ACh signals between successful and failed trials; instead, it abolished the difference in NE-ACh phase synchrony between the successful and failed trials, indicating that NE-ACh phase synchrony is a task-relevant neuromodulatory feature. Chemogenetic inhibition of cholinergic neurons that project to the LC region did not impair the inhibitory control performance, nor did it abolish the difference in NE-ACh phase synchrony between successful or failed trials, further confirming the relevance of NE-ACh phase synchrony to inhibitory control. To understand the possible effect of NE-ACh synchrony on prefrontal population activity, we employed Neuropixels to record from the prefrontal cortex with and without inhibiting LC neurons that project to the basal forebrain during inhibitory control. The LC inhibition reduced the number of prefrontal neurons encoding inhibitory control. Demixed principal component analysis (dPCA) further revealed that population firing patterns representing inhibitory control were impaired by the LC inhibition. Disparities in NE-ACh phase synchrony relevant to inhibitory control occurred only in the prefrontal cortex, but not in the parietal cortex, somatosensory cortex, and the somatosensory thalamus. Taken together, these findings suggest that the LC modulates inhibitory control through its collective effect with cholinergic systems on population activity in the prefrontal cortex. Our results further revealed that NE-ACh phase synchrony is a critical neuromodulatory feature with important implications for cognitive control.
in bioRxiv: Neuroscience on 2024-05-17 00:00:00 UTC.
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RNA editing is a post-transcriptional source of protein diversity and occurs across the animal kingdom. Given the complete profile of mRNA targets and their editing rate in individual cells is unclear, we analyzed single cell RNA transcriptomes from Drosophila larval tonic and phasic glutamatergic motoneuron subtypes to determine the most highly edited targets and identify cell-type specific editing. From ~15,000 genes encoded in the genome, 316 high confidence A-to-I canonical RNA edit sites were identified, with 102 causing missense amino acid changes in proteins regulating membrane excitability, synaptic transmission, and cellular function. Some sites showed 100% editing in single neurons as observed with mRNAs encoding mammalian AMPA receptors. However, most sites were edited at lower levels and generated variable expression of edited and unedited mRNAs within individual neurons. Together, these data provide insights into how the RNA editing landscape alters protein function to modulate the properties of two well-characterized neuronal populations in Drosophila.
in bioRxiv: Neuroscience on 2024-05-17 00:00:00 UTC.
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Concurrent transcranial magnetic stimulation (TMS) with functional magnetic resonance imaging (fMRI) is increasingly being used to study how TMS affects neural processing in local and remote connected brain regions. However, there are many technical challenges that arise when operating this unique combination of techniques. One such challenge is MR head coil compatibility and the image resolution that can be achieved. Here we compare the temporal-signal-to noise-ratio (tSNR) between 3 different MR head coils that can be used with TMS. We show that the 7-channel TMS-dedicated surface coils result in a very high tSNR directly under the TMS and the supplementary coil in comparison to the TxRx and the Magnetica. However, there is low tSNR elsewhere. This field inhomogeneity may not be suitable for all research questions, for example where the aim is to look at distributed neural responses. In these cases, an MR coil with a more homogeneous tSNR such as the Magnetica, may be more appropriate.
in bioRxiv: Neuroscience on 2024-05-17 00:00:00 UTC.
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Pair bonds powerfully modulate health, which becomes particularly important when facing the detrimental effects of aging. To examine the impact of aging on relationship formation and response to loss, we examined behavior in 6-, 12-, and 18-month male and female prairie voles, a monogamous species that forms mating-based pair bonds. We found that older males (18-months) bonded quicker than younger voles, while similarly aged female voles increased partner directed affiliative behaviors. Supporting sex differences in bonding behaviors, we found that males were more likely to sample both partner and novel voles while females were more likely to display partner preference during the initial 20 minutes of the test. Using partner separation to study loss, we observed an erosion of partner preference only in 12-month females, but an overall decrease in partner-directed affiliation in females across all groups, but not in males. Finally, we found that the number of oxytocin, but not vasopressin, cells in the paraventricular hypothalamus increased during aging. These results establish prairie voles as a novel model to study the effects of normal and abnormal aging on pair bonding.
in bioRxiv: Neuroscience on 2024-05-17 00:00:00 UTC.
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Neural entrainment to slow modulations in the amplitude envelope of infant-directed speech is thought to drive early language learning. Most previous research with infants examining speech-brain tracking has been conducted in controlled, experimental settings, which are far from the complex environments of everyday interactions. Whilst recent work has begun to investigate speech-brain tracking to naturalistic speech, this work has been conducted in semi-structured paradigms, where infants listen to live adult speakers, without engaging in free-flowing social interactions. Here, we test the applicability of mTRF modelling to measure speech-brain tracking in naturalistic and bidirectional free-play interactions of 9-12-month-olds with their caregivers. Using a backwards modelling approach, we test individual and generic training procedures, and examine the effects of data quantity and quality on model fitting. We show model fitting is most optimal using an individual approach, trained on continuous segments of interaction data. Corresponding to previous findings, individual models showed significant speech-brain tracking at delta modulation frequencies, but not in alpha and theta bands. These findings open new methods for studying the interpersonal micro-processes that support early language learning. In future work, it will be important to develop a mechanistic framework for understanding how our brains track naturalistic speech during infancy.
in bioRxiv: Neuroscience on 2024-05-17 00:00:00 UTC.
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The pituitary gland (PG) plays a central role in the production and secretion of pubertal hormones, with documented links to the emergence and increase in mental health symptoms known to occur during adolescence. Although much of the literature has focused on examining whole PG volume, recent findings suggest that there are associations among pubertal hormone levels, including dehydroepiandrosterone (DHEA), subregions of the PG, and elevated mental health symptoms (e.g., internalizing symptoms) during adolescence. Surprisingly, studies have not yet examined associations among these factors and increasing transdiagnostic symptomology, despite DHEA being a primary output of the anterior PG. Therefore, the current study sought to fill this gap by examining whether anterior PG volume specifically mediates associations between DHEA levels and changes in dysregulation symptoms in an adolescent sample (N = 114, 9-17 years, Mage = 12.87, SD = 1.88). Following manual tracing of the anterior and posterior PG, structural equation modeling revealed that greater anterior, not posterior, PG volume mediated the association between greater DHEA levels and increasing dysregulation symptoms across time, controlling for baseline dysregulation symptom levels. These results suggest specificity in the role of the anterior PG in adrenarcheal processes that may confer risk for psychopathology during adolescence. This work not only highlights the importance of separately tracing the anterior and posterior PG, but also suggests that transdiagnostic factors like dysregulation are useful in parsing hormone-related increases in mental health symptoms in youth.
in bioRxiv: Neuroscience on 2024-05-17 00:00:00 UTC.
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Age-related structural brain changes may be better captured by assessing complex spatial geometric differences rather than isolated changes to individual regions. We applied a novel analytic method to quantify age-related changes to the spatial anatomy of the brain by measuring expansion and compression of global brain shape and the distance between cross-hemisphere homologous regions. To test how global brain shape and regional distances are affected by aging, we analyzed 2,603 structural MRIs (range: 30-97 years). Increasing age was associated with global shape expansion across inferior-anterior gradients, global compression across superior-posterior gradients, and regional expansion between frontotemporal homologues. Specific patterns of global and regional expansion and compression were further associated with clinical impairment and distinctly related to deficits in various cognitive domains. These findings suggest that changes to the complex spatial anatomy and geometry of the aging brain may be associated with reduced efficiency and cognitive dysfunction in older adults.
in bioRxiv: Neuroscience on 2024-05-17 00:00:00 UTC.
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The functional connectome changes with aging. We systematically evaluated aging related alterations in the functional connectome using a whole-brain connectome network analysis in 39,675 participants in UK Biobank project. We used adaptive dense network discovery tools to identify networks directly associated with aging from resting-state fMRI data. We replicated our findings in 499 participants from the Lifespan Human Connectome Project in Aging study. The results consistently revealed two motor-related subnetworks (both permutation test p-values <0.001) that showed a decline in resting-state functional connectivity (rsFC) with increasing age. The first network primarily comprises sensorimotor and dorsal/ventral attention regions from precentral gyrus, postcentral gyrus, superior temporal gyrus, and insular gyrus, while the second network is exclusively composed of basal ganglia regions, namely the caudate, putamen, and globus pallidus. Path analysis indicates that white matter fractional anisotropy mediates 19.6% (p<0.001, 95% CI [7.6% 36.0%]) and 11.5% (p<0.001, 95% CI [6.3% 17.0%]) of the age-related decrease in both networks, respectively. The total volume of white matter hyperintensity mediates 32.1% (p<0.001, 95% CI [16.8% 53.0%]) of the aging-related effect on rsFC in the first subnetwork.
in bioRxiv: Neuroscience on 2024-05-17 00:00:00 UTC.
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In everyday life, we frequently engage in hybrid search, where we look for multiple items stored in memory (e.g., a mental shopping list) in our visual environment. Across three experiments, we used event-related potentials to better understand the contributions of visual working memory (VWM) and long-term memory (LTM) during the memory search component of hybrid search. Experiments 1 and 2 demonstrated that the FN400, an index of LTM recognition, and the CDA, an index of VWM, increased with memory set size (target load), suggesting that both VWM and LTM are involved in memory search, even when memory load exceeds capacity limitations of VWM. In Experiment 3, we used these electrophysiological indices to test how categorical similarity of targets and distractors affects memory search. The CDA and FN400 were modulated by memory set size only if items resembled targets. This suggests that dissimilar distractor items can be rejected before eliciting a memory search. Together, our findings demonstrate the interplay of VWM and LTM processes during memory search for multiple targets.
in bioRxiv: Neuroscience on 2024-05-17 00:00:00 UTC.
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Mapping the vascular organization of the brain is of great importance across various domains of basic neuroimaging research, diagnostic radiology, and neurology. However, the intricate task of precisely mapping vasculature across brain regions and cortical layers presents formidable challenges, resulting in a limited understanding of neurometabolic factors influencing the brains microvasculature. Addressing this gap, our study investigates whole-brain vascular volume using ferumoxytol-weighted laminar-resolution multi-echo gradient-echo imaging in macaque monkeys. We validate the results with published data for vascular densities and compare them with cytoarchitecture, neuron and synaptic densities. The ferumoxytol-induced change in transverse relaxation rate ({Delta}R2*), an indirect proxy measure of cerebral blood volume (CBV), was mapped onto twelve equivolumetric laminar cortical surfaces. Our findings reveal that CBV varies 3-fold across the brain, with the highest vascular volume observed in the inferior colliculus and lowest in the corpus callosum. In the cerebral cortex, CBV is notably high in early primary sensory areas and low in association areas responsible for higher cognitive functions. Classification of CBV into distinct groups unveils extensive replication of translaminar vascular network motifs, suggesting distinct computational energy supply requirements in areas with varying cytoarchitecture types. Regionally, baseline R2* and CBV exhibit positive correlations with neuron density and negative correlations with receptor densities. Adjusting image resolution based on the critical sampling frequency of penetrating cortical vessels, allows us to delineate approximately 30% of the arterial-venous vessels. Collectively, these results mark significant methodological and conceptual advancements, contributing to the refinement of cerebrovascular MRI. Furthermore, our study establishes a linkage between neurometabolic factors and the vascular network architecture in the primate brain.
in bioRxiv: Neuroscience on 2024-05-17 00:00:00 UTC.
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Neuronal activity in the olfactory bulb (OB) drives coordinated activity in the hippocampal-prefrontal network during early development. Inhibiting OB output in neonatal mice disrupts functional development of the hippocampal formation as well as cognitive abilities. These impairments manifest early in life and resemble dysfunctions of the hippocampus and the prefrontal cortex that have been linked to neuropsychiatric disorders. Thus, we investigated a disease mouse model and asked whether activity in the OB might be altered, thereby contributing to the dysfunctional development of the hippocampal-prefrontal network. We addressed this question by combining in vivo electrophysiology with behavioral assessment of immune-challenged Disc1+/- mice that mimic the dual genetic-environmental etiology of neuropsychiatric disorders. In wildtype mice, we found high DISC1 expression levels in OB projection neurons during development. Furthermore, neuronal and network activity in the OB, as well as the drive from the bulb to the hippocampal-prefrontal network were reduced in immune-challenged Disc1+/- mice during early development. This early deficit did not affect odor-evoked activity and odor perception but resulted in impaired long-term odor memory. We propose that reduced endogenous activity in the developing OB contributes to altered maturation of the hippocampal-prefrontal network, leading to memory impairment in immune-challenged Disc1+/- mice.
in bioRxiv: Neuroscience on 2024-05-17 00:00:00 UTC.
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Neurofeedback (NF) training based on motor imagery is increasingly used in neurorehabilitation with the aim to improve motor functions. However, the neuroplastic changes underpinning these improvements are poorly understood. Here, we used mental finger individuation, i.e., the selective facilitation of single finger representations without producing overt movements, as a model to study neuroplasticity induced by NF. To enhance mental finger individuation, we used transcranial magnetic stimulation (TMS)-based NF training. During motor imagery of individual finger movements, healthy participants were provided visual feedback on the size of motor evoked potentials, reflecting their finger-specific corticospinal excitability. We found that TMS-NF improved the top-down activation of finger-specific representations. First, intracortical inhibitory circuits in the primary motor cortex were tuned after training such that inhibition was selectively reduced for the finger that was mentally activated. Second, motor imagery finger representations in sensorimotor areas assessed with functional MRI became more distinct after training. Together, our results indicate that the neural underpinnings of finger individuation, a well-known model system for neuroplasticity, can be modified using TMS-NF guided motor imagery training. These findings demonstrate that TMS-NF induces neuroplasticity in the sensorimotor system, highlighting the promise of TMS-NF on the recovery of fine motor function.
in bioRxiv: Neuroscience on 2024-05-17 00:00:00 UTC.
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Behavioural variant frontotemporal dementia (bvFTD) is a neurodegenerative disorder characterized by behavioural changes and atrophy in brain regions important for decision-making. Computations such as trading off between larger later (LL) and smaller sooner (SS) rewards, called delay discounting in behavioural economics, might be heavily impaired by bvFTD. In this cross-sectional study, our objectives were to investigate (1) whether bvFTD patients show higher delay discounting than healthy controls, (2) whether this maladaptive discounting correlates with impulsivity-related bvFTD symptoms, and (3) in which brain regions atrophy is related to bvFTD's steeper discounting. BvFTD patients (N=24) and matched controls (N=18) performed two delay discounting tasks: one with monetary rewards and one with food rewards. We compared discount rates (log(k)) in bvFTD patients and controls and tested their correlations with symptoms. We used participants' structural MRI data and applied whole-brain mediation analyses to investigate brain structures mediating the effect of bvFTD on delay discounting. For both monetary and food rewards, delay discounting was significantly higher in bvFTD patients than in healthy controls. BvFTD patients' higher discounting of both money and food was associated with their greater disinhibition and eating behaviour changes. Whole-brain mediation analyses revealed that (1) several brain regions (left thalamic pulvinar, left parahippocampal cortex, right temporal lobe) were predictive of steeper discounting of both money and food and (2) grey matter density in these brain regions, including most prominently the medial pulvinar, mediated the effect of bvFTD on discounting. The impulsive preference for sooner rewards captured by delay discounting might constitute a common mechanism of the behavioural symptoms of inhibition deficit and eating behaviour changes in bvFTD. Future studies could further investigate the potential role of medial pulvinar structural modifications as a transdiagnostic marker and a therapeutic target of impulsivity troubles.
in bioRxiv: Neuroscience on 2024-05-17 00:00:00 UTC.
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Adaptive decision making relies on dynamic updating of learned associations where environmental cues come to predict positive and negatively valenced stimuli, such as food or threat. Flexible cue-guided behaviors depend on a network of brain systems, including dopamine signaling in the striatum, which is critical for learning and maintenance of conditioned behaviors. Critically, it remains unclear how dopamine signaling encodes multi-valent, dynamic learning contexts, where positive and negative associations must be rapidly disambiguated. To understand this, we employed a Pavlovian discrimination paradigm, where cues predicting positive and negative outcomes were intermingled during conditioning sessions, and their meaning was serially reversed across training. We found that rats readily distinguished these cues, and updated their behavior rapidly upon valence reversal. Using fiber photometry, we recorded dopamine signaling in three major striatal subregions - the dorsolateral striatum (DLS), the nucleus accumbens core, and the nucleus accumbens medial shell - and found heterogeneous responses to positive and negative conditioned cues and their predicted outcomes. Valence ambiguity introduced by cue reversal reshaped striatal dopamine on different timelines: nucleus accumbens core and shell signals updated more readily than those in the DLS. Together, these results suggest that striatal dopamine flexibly encodes multi-valent learning contexts, and these signals are dynamically modulated by changing contingencies to resolve ambiguity about the meaning of environmental cues.
in bioRxiv: Neuroscience on 2024-05-17 00:00:00 UTC.
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The strength of inhibitory neurotransmission depends on intracellular neuronal chloride concentration, primarily regulated by the activity of cation-chloride cotransporters NKCC1 and KCC2. Brain-derived neurotrophic factor (BDNF) influences the functioning of these co-transporters. BDNF is synthesized from precursor proteins (proBDNF), which undergo proteolytic cleavage to yield mature BDNF (mBDNF). While previous studies have indicated the involvement of BDNF signaling in the activity of KCC2, its specific mechanisms are unclear. We investigated the interplay between both forms of BDNF and chloride homeostasis in rat hippocampal neurons and in-utero electroporated cortices of rat pups, spanning the behavioral, cellular, and molecular levels. We found that both pro- and mBDNF play a comparable role in immature neurons by inhibiting the capacity of neurons to extrude chloride. Additionally, proBDNF increases the endocytosis of KCC2 while maintaining a depolarizing shift of EGABA in maturing neurons. Behaviorally, proBDNF-electroporated rat pups in the somatosensory cortex exhibit sensory deficits delayed huddling and cliff avoidance. These findings emphasize the role of BDNF signaling in regulating chloride transport through the modulation of KCC2. In summary, this study provides valuable insights into the intricate interplay between BDNF, chloride homeostasis, and inhibitory synaptic transmission, shedding light on the underlying cellular mechanisms involved.
in bioRxiv: Neuroscience on 2024-05-17 00:00:00 UTC.
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The influential concept of a cognitive map envisions that the brain builds mental representations of objects, barriers, and goals. This idea has been formalized in a range of computational models that show how such representations can be useful for guiding goal-directed behavior, for instance by planning novel routes to maximize long-run rewards. One key feature of flexible cognitive representations generally is that they exploit compositionality -the ability to build complex structures by recombining simpler parts. However, how this principle plays out in neural representations of cognitive maps and map-based planning remains largely unexplored. Indeed, as we show here, compositionality can be difficult to reconcile with efficient planning: because reuse tends to oppose flexibility, it is challenging to construct a compositional representation of the environment which is also organized in a way that enables generalizability and efficient planning. Here, we propose a novel model for efficiently creating and planning with compositional predictive maps, and further show that it successfully simulates various aspects of response fields in the medial entorhinal cortex, particularly object vector cells and grid cells. The model treats each object as an alteration to a baseline map linked to open space, creating complete predictive maps by combining object-related representations compositionally. Overall, this work provides a comprehensive and realistic model for efficient model learning and model-based planning in animals, and offers insights into the brain processes supporting efficient, flexible planning using compositional predictive maps.
in bioRxiv: Neuroscience on 2024-05-17 00:00:00 UTC.
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Minimally invasive, high-bandwidth brain-computer-interface (BCI) devices can revolutionize human applications. With orders-of-magnitude improvements in volumetric efficiency over other BCI technologies, we developed a 50-m-thick, mechanically flexible micro-electrocorticography (ECoG) BCI, integrating 256x256 electrodes, signal processing, data telemetry, and wireless powering on a single complementary metal-oxide-semiconductor (CMOS) substrate containing 65,536 recording and 16,384 stimulation channels, from which we can simultaneously record up to 1024 channels at a given time. Fully implanted below the dura, our chip is wirelessly powered, communicating bi-directionally with an external relay station outside the body. We demonstrated chronic, reliable recordings for up to two weeks in pigs and up to two months in behaving non-human primates from somatosensory, motor, and visual cortices, decoding brain signals at high spatiotemporal resolution.
in bioRxiv: Neuroscience on 2024-05-17 00:00:00 UTC.
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Visual cortex is thought to show both dorsoventral and hemispheric modularity, but it is not known if the same functional modules emerge spontaneously from an unsupervised network analysis, or how they interact when saccades necessitate increased sharing of spatial information. Here, we address these issues by applying graph theory analysis to fMRI data obtained while human participants decided whether an object's shape or orientation changed, with or without an intervening saccade across the object. BOLD activation from 50 vision-related cortical nodes was used to identify local and global network properties. Modularity analysis revealed three sub-networks during fixation: a bilateral parietofrontal network linking areas implicated in visuospatial processing and two lateralized occipitotemporal networks linking areas implicated in object feature processing. When horizontal saccades required visual comparisons between visual hemifields, functional interconnectivity and information transfer increased, and the two lateralized ventral modules became functionally integrated into a single bilateral sub-network. This network included between-module connectivity hubs in lateral intraparietal cortex and dorsomedial occipital areas previously implicated in transsaccadic integration. These results provide support for functional modularity in the visual system and show that the hemispheric sub-networks are modified and functionally integrated during saccades.
in bioRxiv: Neuroscience on 2024-05-17 00:00:00 UTC.
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Friedreich's ataxia is a hereditary neurodegenerative disorder resulting from reduced levels of the protein frataxin due to an expanded GAA repeat in the FXN gene. This deficiency causes progressive degeneration of specific neuronal populations in the cerebellum and the consequent loss of movement coordination and equilibrium, some of the main symptoms observed in affected individuals. Similar to other neurodegenerative diseases, previous studies suggest that glial cells could be involved in the neurodegenerative process and disease progression in Friedreich's ataxia. In this work, we have followed and characterized the progression of changes in the cerebellar cortex of the latest Friedreich's ataxia humanized mouse model, the YG8-800 (Fxnnull:YG8s(GAA)>800), which carries a human FXN transgene containing more than 800 GAA repeats. Comparative analyses of behavioral, histopathological, and biochemical parameters were conducted between Y47R control and YG8-800 mice at different time points. Our findings revealed that the YG8-800 mice display an ataxic phenotype, characterized by poor motor coordination, lower body weight, cerebellar atrophy, neuronal loss, and changes in synaptic proteins. Additionally, early activation of glial cells, predominantly astrocytes and microglia, was observed preceding neuronal degeneration along with an increased expression of key pro-inflammatory cytokines and downregulation of neurotrophic factors. Together, our results show how the YG8-800 mouse model exhibits a stronger phenotype than previous experimental murine models, reliably recapitulating some of the features observed in the human condition. Accordingly, this humanized model could represent a valuable tool to study Friedreich's ataxia molecular disease mechanisms and for preclinical evaluation of possible therapies.
in bioRxiv: Neuroscience on 2024-05-17 00:00:00 UTC.
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Human behavior can be remarkably shaped by experience, such as the removal of sensory input. Many studies of conditions such as stroke, limb amputation, and vision loss have examined how the removal of input changes brain function. However, an important question has yet to be answered: when input is lost, does the brain change its connectivity to preferentially use some remaining inputs over others? In individuals with healthy vision, the central portion of the retina is preferentially used for everyday visual tasks, due to its ability to discriminate fine details. However, when central vision is lost in conditions like macular degeneration, peripheral vision must be relied upon for those everyday tasks, with certain portions receiving preferential usage over others. Using resting-state fMRI collected during total darkness, we examined how deprivation and preferential usage influence the intrinsic functional connectivity of sensory cortex by studying individuals with selective vision loss due to late stages of macular degeneration. We found that cortical regions representing spared portions of the peripheral retina, regardless of whether they are preferentially used, exhibit plasticity of intrinsic functional connectivity in macular degeneration. Cortical representations of spared peripheral retinal locations showed stronger connectivity to MT, a region involved in processing motion. These results suggest that long-term loss of central vision can produce widespread effects throughout spared representations in early visual cortex, regardless of whether those representations are preferentially used. These findings support the idea that connections to visual cortex maintain the capacity for change well after critical periods of visual development.
in bioRxiv: Neuroscience on 2024-05-17 00:00:00 UTC.
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Despite its clinical adoption, there remains a lack of understanding about how tibial nerve stimulation (TNS) improves lower urinary tract symptoms. Current evidence indicates that TNS ameliorates overactive bladder by the inhibition of micturition related activity in the brainstem and spinal cord. We present a detailed computational model and demonstrate that TNS can also induce excitatory effects via brainstem specific activity, proposing non-invasive neuromodulation as a treatment for urinary retention.
in bioRxiv: Neuroscience on 2024-05-17 00:00:00 UTC.
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Brain Sciences, Vol. 14, Pages 510: Virtual Reality Exposure Therapy for Treating Fear of Contamination Disorders: A Systematic Review of Healthy and Clinical Populations
Brain Sciences doi: 10.3390/brainsci14050510
Authors:
Francesca Ferraioli
Laura Culicetto
Luca Cecchetti
Alessandra Falzone
Francesco Tomaiuolo
Angelo Quartarone
Carmelo Mario Vicario
Virtual Reality Exposure Therapy (VRET), particularly immersive Virtual Reality Exposure Therapy (iVRET), has gained attraction as an innovative approach in exposure therapy (ET), notably for some anxiety disorders with a fear of contamination component, such as spider phobia (SP) and obsessive&ndash;compulsive disorder (OCD). This systematic work investigates iVRET&rsquo;s effectiveness in modulating disgust emotion&mdash;a shared aberrant feature across these disorders. Recent reviews have evaluated VRET&rsquo;s efficacy against in vivo ET. However, emerging evidence also highlights iVRET&rsquo;s potential in diminishing atypical disgust and related avoidance behaviors, expanding beyond traditional fear-focused outcomes. Our systematic synthesis, adhering to PRISMA guidelines, aims to fill this gap by assessing iVRET&rsquo;s efficacy in regulating disgust emotion within both clinical and at-risk populations, identified through standardized questionnaires and subjective disgust ratings. This research analyzes data from eight studies on clinical populations and five on healthy populations, offering an insight into iVRET&rsquo;s potential to mitigate the aberrant disgust response, a common transdiagnostic feature in varied psychopathologies. The findings support iVRET&rsquo;s clinical relevance in disgust management, providing evidence for a broader therapeutic application of iVRET and pointing out the need for more focused and complete investigations in this emergent field.
in Brain Sciences on 2024-05-17 00:00:00 UTC.
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Brain Sciences, Vol. 14, Pages 509: From Connectivity to Controllability: Unraveling the Brain Biomarkers of Major Depressive Disorder
Brain Sciences doi: 10.3390/brainsci14050509
Authors:
Chunyu Pan
Ying Ma
Lifei Wang
Yan Zhang
Fei Wang
Xizhe Zhang
Major Depressive Disorder (MDD) is a significant neurological condition associated with aberrations in brain functional networks. Traditional studies have predominantly analyzed these from a network topology perspective. However, given the brain&rsquo;s dynamic and complex nature, exploring its mechanisms from a network control standpoint provides a fresh and insightful framework. This research investigates the integration of network controllability and machine learning to pinpoint essential biomarkers for MDD using functional magnetic resonance imaging (fMRI) data. By employing network controllability methods, we identify crucial brain regions that are instrumental in facilitating transitions between brain states. These regions demonstrate the brain&rsquo;s ability to navigate various functional states, emphasizing the utility of network controllability metrics as potential biomarkers. Furthermore, these metrics elucidate the complex dynamics of MDD and support the development of precision medicine strategies that incorporate machine learning to improve the precision of diagnostics and the efficacy of treatments. This study underscores the value of merging machine learning with network neuroscience to craft personalized interventions that align with the unique pathological profiles of individuals, ultimately enhancing the management and treatment of MDD.
in Brain Sciences on 2024-05-17 00:00:00 UTC.
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Brain Sciences, Vol. 14, Pages 508: EEG Changes in Migraine—Can EEG Help to Monitor Attack Susceptibility?
Brain Sciences doi: 10.3390/brainsci14050508
Authors:
Thomas C. van den Hoek
Mark van de Ruit
Gisela M. Terwindt
Else A. Tolner
Migraine is a highly prevalent brain condition with paroxysmal changes in brain excitability believed to contribute to the initiation of an attack. The attacks and their unpredictability have a major impact on the lives of patients. Clinical management is hampered by a lack of reliable predictors for upcoming attacks, which may help in understanding pathophysiological mechanisms to identify new treatment targets that may be positioned between the acute and preventive possibilities that are currently available. So far, a large range of studies using conventional hospital-based EEG recordings have provided contradictory results, with indications of both cortical hyper- as well as hypo-excitability. These heterogeneous findings may largely be because most studies were cross-sectional in design, providing only a snapshot in time of a patient&rsquo;s brain state without capturing day-to-day fluctuations. The scope of this narrative review is to (i) reflect on current knowledge on EEG changes in the context of migraine, the attack cycle, and underlying pathophysiology; (ii) consider the effects of migraine treatment on EEG features; (iii) outline challenges and opportunities in using EEG for monitoring attack susceptibility; and (iv) discuss future applications of EEG in home-based settings.
in Brain Sciences on 2024-05-17 00:00:00 UTC.
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Brain Sciences, Vol. 14, Pages 507: Spatial-Temporal Characteristics of Brain Activity in Autism Spectrum Disorder Based on Hidden Markov Model and Dynamic Graph Theory: A Resting-State fMRI Study
Brain Sciences doi: 10.3390/brainsci14050507
Authors:
Shiting Qian
Qinqin Yang
Congbo Cai
Jiyang Dong
Shuhui Cai
Autism spectrum disorder (ASD) is a common neurodevelopmental disorder. Functional magnetic resonance imaging (fMRI) can be used to measure the temporal correlation of blood-oxygen-level-dependent (BOLD) signals in the brain to assess the brain&rsquo;s intrinsic connectivity and capture dynamic changes in the brain. In this study, the hidden Markov model (HMM) and dynamic graph (DG) theory are used to study the spatial-temporal characteristics and dynamics of brain networks based on dynamic functional connectivity (DFC). By using HMM, we identified three typical brain states for ASD and healthy control (HC). Furthermore, we explored the correlation between HMM time-varying properties and clinical autism scale scores. Differences in brain topological characteristics and dynamics between ASD and HC were compared by DG analysis. The experimental results indicate that ASD is more inclined to enter a strongly connected HMM brain state, leading to the isolation of brain networks and alterations in the topological characteristics of brain networks, such as default mode network (DMN), ventral attention network (VAN), and visual network (VN). This work suggests that using different data-driven methods based on DFC to study brain network dynamics would have better information complementarity, which can provide a new direction for the extraction of neuro-biomarkers in the early diagnosis of ASD.
in Brain Sciences on 2024-05-17 00:00:00 UTC.
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Brain Sciences, Vol. 14, Pages 506: The Effect of Rhythmic Audio-Visual Stimulation on Inhibitory Control: An ERP Study
Brain Sciences doi: 10.3390/brainsci14050506
Authors:
Yifan Wang
Di Wu
Kewei Sun
Yan Zhu
Xianglong Chen
Wei Xiao
Inhibitory control, as an essential cognitive ability, affects the development of higher cognitive functions. Rhythmic perceptual stimulation has been used to improve cognitive abilities. It is unclear, however, whether it can be used to improve inhibitory control. This study used the Go/NoGo task and the Stroop task to assess various levels of inhibitory control using rhythmic audio-visual stimuli as the stimulus mode. Sixty subjects were randomly divided into three groups to receive 6 Hz, 10 Hz, and white noise stimulation for 30 min. Two tasks were completed by each subject both before and after the stimulus. Before and after the task, closed-eye resting EEG data were collected. The results showed no differences in behavioral and EEG measures of the Go/NoGo task among the three groups. While both 6 Hz and 10 Hz audio-visual stimulation reduced the conflict effect in the Stroop task, only 6 Hz audio-visual stimulation improved the amplitude of the N2 component and decreased the conflict score. Although rhythmic audio-visual stimulation did not enhance response inhibition, it improved conflict inhibition.
in Brain Sciences on 2024-05-17 00:00:00 UTC.
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in eNeuro on 2024-05-16 16:30:22 UTC.
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The corpus callosum is composed of several subregions, distinct in cellular and functional organization. This organization scheme may render these subregions differentially vulnerable to the aging process. Callosal integrity may be further compromised by cardiovascular risk factors, which negatively influence white matter health. Here, we test for heterochronicity of aging, hypothesizing an anteroposterior gradient of vulnerability to aging that may be altered by the effects of cardiovascular health. In 174 healthy adults across the adult lifespan (mean age = 53.56 ± 18.90; range, 20–94 years old, 58.62% women), pulse pressure (calculated as participant's systolic minus diastolic blood pressure) was assessed to determine cardiovascular risk. A deterministic tractography approach via diffusion-weighted imaging was utilized to extract fractional anisotropy (FA), radial diffusivity (RD), and axial diffusivity (AD) from each of five callosal subregions, serving as estimates of microstructural health. General linear models tested the effects of age, hypertension, and pulse pressure on these cross-sectional metrics. We observed no significant effect of hypertensive diagnosis on callosal microstructure. We found a significant main effect of age and an age–pulse pressure interaction whereby older age and elevated pulse pressure were associated with poorer FA, AD, and RD. Age effects revealed nonlinear components and occurred along an anteroposterior gradient of severity in the callosum. This gradient disappeared when pulse pressure was considered. These results indicate that age-related deterioration across the callosum is regionally variable and that pulse pressure, a proxy of arterial stiffness, exacerbates this aging pattern in a large lifespan cohort.
in eNeuro on 2024-05-16 16:30:22 UTC.
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by Tara Hameed, Natasha Motsi, Elaine Bignell, Reiko J. Tanaka
Quantifying fungal growth underpins our ability to effectively treat severe fungal infections. Current methods quantify fungal growth rates from time-course morphology-specific data, such as hyphal length data. However, automated large-scale collection of such data lies beyond the scope of most clinical microbiology laboratories. In this paper, we propose a mathematical model of fungal growth to estimate morphology-specific growth rates from easy-to-collect, but indirect, optical density (OD600) data of Aspergillus fumigatus growth (filamentous fungus). Our method accounts for OD600 being an indirect measure by explicitly including the relationship between the indirect OD600 measurements and the calibrating true fungal growth in the model. Therefore, the method does not require de novo generation of calibration data. Our model outperformed reference models at fitting to and predicting OD600 growth curves and overcame observed discrepancies between morphology-specific rates inferred from OD600 versus directly measured data in reference models that did not include calibration.
in PLoS Computational Biology on 2024-05-16 14:00:00 UTC.
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by Vishal Rana, Jianhao Peng, Chao Pan, Hanbaek Lyu, Albert Cheng, Minji Kim, Olgica Milenkovic
Dictionary learning (DL), implemented via matrix factorization (MF), is commonly used in computational biology to tackle ubiquitous clustering problems. The method is favored due to its conceptual simplicity and relatively low computational complexity. However, DL algorithms produce results that lack interpretability in terms of real biological data. Additionally, they are not optimized for graph-structured data and hence often fail to handle them in a scalable manner.
In order to address these limitations, we propose a novel DL algorithm called online convex network dictionary learning (online cvxNDL). Unlike classical DL algorithms, online cvxNDL is implemented via MF and designed to handle extremely large datasets by virtue of its online nature. Importantly, it enables the interpretation of dictionary elements, which serve as cluster representatives, through convex combinations of real measurements. Moreover, the algorithm can be applied to data with a network structure by incorporating specialized subnetwork sampling techniques.
To demonstrate the utility of our approach, we apply cvxNDL on 3D-genome RNAPII ChIA-Drop data with the goal of identifying important long-range interaction patterns (long-range dictionary elements). ChIA-Drop probes higher-order interactions, and produces data in the form of hypergraphs whose nodes represent genomic fragments. The hyperedges represent observed physical contacts. Our hypergraph model analysis has the objective of creating an interpretable dictionary of long-range interaction patterns that accurately represent global chromatin physical contact maps. Through the use of dictionary information, one can also associate the contact maps with RNA transcripts and infer cellular functions.
To accomplish the task at hand, we focus on RNAPII-enriched ChIA-Drop data from Drosophila Melanogaster S2 cell lines. Our results offer two key insights. First, we demonstrate that online cvxNDL retains the accuracy of classical DL (MF) methods while simultaneously ensuring unique interpretability and scalability. Second, we identify distinct collections of proximal and distal interaction patterns involving chromatin elements shared by related processes across different chromosomes, as well as patterns unique to specific chromosomes. To associate the dictionary elements with biological properties of the corresponding chromatin regions, we employ Gene Ontology (GO) enrichment analysis and perform multiple RNA coexpression studies.
in PLoS Computational Biology on 2024-05-16 14:00:00 UTC.
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by Yuchao Li, Difan Deng, Chris Tina Höfer, Jihye Kim, Won Do Heo, Quanbin Xu, Xuedong Liu, Zhike Zi
Cells use signaling pathways to sense and respond to their environments. The transforming growth factor-β (TGF-β) pathway produces context-specific responses. Here, we combined modeling and experimental analysis to study the dependence of the output of the TGF-β pathway on the abundance of signaling molecules in the pathway. We showed that the TGF-β pathway processes the variation of TGF-β receptor abundance using Liebig’s law of the minimum, meaning that the output-modifying factor is the signaling protein that is most limited, to determine signaling responses across cell types and in single cells. We found that the abundance of either the type I (TGFBR1) or type II (TGFBR2) TGF-β receptor determined the responses of cancer cell lines, such that the receptor with relatively low abundance dictates the response. Furthermore, nuclear SMAD2 signaling correlated with the abundance of TGF-β receptor in single cells depending on the relative expression levels of TGFBR1 and TGFBR2. A similar control principle could govern the heterogeneity of signaling responses in other signaling pathways.
in PLoS Computational Biology on 2024-05-16 14:00:00 UTC.
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by Jason M. Müller, Katharina Moos, Till Baar, Kerstin C. Maier, Kristina Zumer, Achim Tresch
The eukaryotic mRNA life cycle includes transcription, nuclear mRNA export and degradation. To quantify all these processes simultaneously, we perform thiol-linked alkylation after metabolic labeling of RNA with 4-thiouridine (4sU), followed by sequencing of RNA (SLAM-seq) in the nuclear and cytosolic compartments of human cancer cells. We develop a model that reliably quantifies mRNA-specific synthesis, nuclear export, and nuclear and cytosolic degradation rates on a genome-wide scale. We find that nuclear degradation of polyadenylated mRNA is negligible and nuclear mRNA export is slow, while cytosolic mRNA degradation is comparatively fast. Consequently, an mRNA molecule generally spends most of its life in the nucleus. We also observe large differences in the nuclear export rates of different 3’UTR transcript isoforms. Furthermore, we identify genes whose expression is abruptly induced upon metabolic labeling. These transcripts are exported substantially faster than average mRNAs, suggesting the existence of alternative export pathways. Our results highlight nuclear mRNA export as a limiting factor in mRNA metabolism and gene regulation.
in PLoS Computational Biology on 2024-05-16 14:00:00 UTC.
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by Ava M. Hoffman, Carrie Wright
in PLoS Computational Biology on 2024-05-16 14:00:00 UTC.
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by Hana Rozhoňová, Carlos Martí-Gómez, David M. McCandlish, Joshua L. Payne
The standard genetic code defines the rules of translation for nearly every life form on Earth. It also determines the amino acid changes accessible via single-nucleotide mutations, thus influencing protein evolvability—the ability of mutation to bring forth adaptive variation in protein function. One of the most striking features of the standard genetic code is its robustness to mutation, yet it remains an open question whether such robustness facilitates or frustrates protein evolvability. To answer this question, we use data from massively parallel sequence-to-function assays to construct and analyze 6 empirical adaptive landscapes under hundreds of thousands of rewired genetic codes, including those of codon compression schemes relevant to protein engineering and synthetic biology. We find that robust genetic codes tend to enhance protein evolvability by rendering smooth adaptive landscapes with few peaks, which are readily accessible from throughout sequence space. However, the standard genetic code is rarely exceptional in this regard, because many alternative codes render smoother landscapes than the standard code. By constructing low-dimensional visualizations of these landscapes, which each comprise more than 16 million mRNA sequences, we show that such alternative codes radically alter the topological features of the network of high-fitness genotypes. Whereas the genetic codes that optimize evolvability depend to some extent on the detailed relationship between amino acid sequence and protein function, we also uncover general design principles for engineering nonstandard genetic codes for enhanced and diminished evolvability, which may facilitate directed protein evolution experiments and the bio-containment of synthetic organisms, respectively.
in PLoS Biology on 2024-05-16 14:00:00 UTC.
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by Huagen Wang, Xiaoyan Wu, Jiahua Xu, Ruida Zhu, Sihui Zhang, Zhenhua Xu, Xiaoqin Mai, Shaozheng Qin, Chao Liu
People tend to intervene in others’ injustices by either punishing the transgressor or helping the victim. Injustice events often occur under stressful circumstances. However, how acute stress affects a third party’s intervention in injustice events remains open. Here, we show a stress-induced shift in third parties’ willingness to engage in help instead of punishment by acting on emotional salience and central-executive and theory-of-mind networks. Acute stress decreased the third party’s willingness to punish the violator and the severity of the punishment and increased their willingness to help the victim. Computational modeling revealed a shift in preference of justice recovery from punishment the offender toward help the victim under stress. This finding is consistent with the increased dorsolateral prefrontal engagement observed with higher amygdala activity and greater connectivity with the ventromedial prefrontal cortex in the stress group. A brain connectivity theory-of-mind network predicted stress-induced justice recovery in punishment. Our findings suggest a neurocomputational mechanism of how acute stress reshapes third parties’ decisions by reallocating neural resources in emotional, executive, and mentalizing networks to inhibit punishment bias and decrease punishment severity.
in PLoS Biology on 2024-05-16 14:00:00 UTC.
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Objective
Although accumulating evidence implicating altered gut microbiota in human immunodeficiency virus (HIV) infection and neurodegenerative disorders; however, the association between dysbiosis of the gut microbiota and metabolites in the pathogenesis of HIV-associated neurocognitive disorder (HAND) remains unclear.
Methods
Fecal and plasma samples were obtained from 3 cohorts (HAND, HIV–non-HAND, and healthy controls), metagenomic analysis and metabolomic profiling were performed to investigate alterations in the gut microbial composition and circulating metabolites in HAND.
Results
The gut microbiota of people living with HIV (PLWH) had an increased relative abundance of Prevotella and a decreased relative abundance of Bacteroides. In contrast, Prevotella and Megamonas were substantially decreased, and Bacteroides and Phocaeicola were increased in HAND patients. Moreover, untargeted metabolomics identified several neurotransmitters and certain amino acids associated with neuromodulation, and the differential metabolic pathways of amino acids associated with neurocognition were depleted in HAND patients. Notably, most neuromodulatory metabolites are associated with an altered abundance of specific gut bacteria.
Interpretation
Our findings provide new insights into the intricate interplay between the gut and microbiome-brain axis in the pathogenesis of HAND, highlighting the potential for developing novel therapeutic strategies that specifically target the gut microbiota. ANN NEUROL 2024
in Annals of Neurology on 2024-05-16 12:29:53 UTC.
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in Annals of Neurology on 2024-05-16 12:20:14 UTC.
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Vitamin D functions as a prohormone that promotes bone mineralization by regulating calcium and phosphate levels in the skeletal system. It is a fat-soluble vitamin that is required for immunomodulation, cytokine regulation, and cell proliferation. As a result, Vitamin D is a powerful hormone with pleiotropic effects that improve overall health. Sepsis is the leading cause of death in critically unwell people. According to a recent study, numerous trace minerals and nutrients have the ability to alter the human body, and supplementing these nutrients can improve the prognosis of sepsis patients. A considerable number of patients in the intensive care unit (ICU) have low vitamin D levels, a frequent condition that can increase the risk of infectious diseases. According to various studies, severely ill patients admitted to the ICU who have a vitamin D deficiency are at a higher risk of requiring mechanical ventilation and facing a higher likelihood of mortality. Nonetheless, the connection between insufficient vitamin D levels and mortality in sepsis patients remains a topic of debate.
in F1000Research on 2024-05-16 11:11:14 UTC.
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Objective
We aimed to evaluate the association between rescue therapy (RT) and functional outcomes compared to medical management (MM) in patients presenting after failed mechanical thrombectomy (MT).
Methods
This cross-sectional study utilized prospectively collected and maintained data from the Society of Vascular and Interventional Neurology Registry, spanning from 2011 to 2021. The cohort comprised patients with large vessel occlusions (LVOs) with failed MT. The primary outcome was the shift in the degree of disability, as gauged by the modified Rankin Scale (mRS) at 90 days. Additional outcomes included functional independence (90-day mRS score of 0–2), symptomatic intracranial hemorrhage (sICH), and 90-day mortality.
Results
Of a total of 7,018 patients, 958 presented failed MT and were included in the analysis. The RT group comprised 407 (42.4%) patients, and the MM group consisted of 551 (57.5%) patients. After adjusting for confounders, the RT group showed a favorable shift in the overall 90-day mRS distribution (adjusted common odds ratio = 1.79, 95% confidence interval [CI] = 1.32–2.45, p < 0.001) and higher rates of functional independence (RT: 28.8% vs MM: 15.7%, adjusted odds ratio [aOR] = 1.93, 95% CI = 1.21–3.07, p = 0.005) compared to the MM group. RT also showed lower rates of sICH (RT: 3.8% vs MM: 9.1%, aOR = 0.52, 95% CI = 0.28–0.97, p = 0.039) and 90-day mortality (RT: 33.4% vs MM: 45.5%, aOR = 0.61, 95% CI = 0.42–0.89, p = 0.009).
Interpretation
Our findings advocate for the utilization of RT as a potential treatment strategy for cases of LVO resistant to first-line MT techniques. Prospective studies are warranted to validate these observations and optimize the endovascular approach for failed MT patients. ANN NEUROL 2024
in Annals of Neurology on 2024-05-16 10:09:31 UTC.
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Author(s): Albert von Kenne, Markus Bär, and Thomas Niedermayer
A model for coordinated motion of cilia is examined in this work. In this model, wave dynamics of cilia are represented by motions of microspheres elastically bound to circular orbits that are inclined with respect to a no-slip surface. Parameters are explored with analytical studies and simulations. The authors demonstrate traveling waves whose dynamics and direction may be tuned by the elasticity.
[Phys. Rev. E 109, 054407] Published Thu May 16, 2024
in Physical Review E: Biological physics on 2024-05-16 10:00:00 UTC.
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We investigate the association between brain entropy (BEN) estimated from resting-state fMRI and pain intensity in a sample including young adults, middle-aged participants, and elders. Main results show that the interaction between age and pain intensity is related to BEN increase in pain-related brain regions. Further investigation showed that, in young adults, pain intensity is related to BEN decrease, whereas in middle-aged participants and elders, pain intensity is related to BEN increase.
Abstract
Pain is a multidimensional subjective experience sustained by multiple brain regions involved in different aspects of pain experience. We used brain entropy (BEN) estimated from resting-state fMRI (rsfMRI) data to investigate the neural correlates of pain experience. BEN was estimated from rs-fMRI data provided by two datasets with different age range: the Human Connectome Project-Young Adult (HCP-YA) and the Human Connectome project-Aging (HCP-A) datasets. Retrospective assessment of experienced pain intensity was retrieved from both datasets. No main effect of pain intensity was observed. The interaction between pain and age, however, was related to increased BEN in several pain-related brain regions, reflecting greater variability of spontaneous brain activity. Dividing the sample into a young adult group (YG) and a middle age-aging group (MAG) resulted in two divergent patterns of pain–BEN association: In the YG, pain intensity was related to reduced BEN in brain regions involved in the sensory processing of pain; in the MAG, pain was associated with increased BEN in areas related to both sensory and cognitive aspects of pain experience.
in Journal of Neuroscience Research on 2024-05-16 06:28:43 UTC.
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Journal of Neurophysiology, Volume 131, Issue 5, Page 948-949, May 2024.
in Journal of Neurophysiology on 2024-05-16 05:59:52 UTC.
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Journal of Neurophysiology, Volume 131, Issue 5, Page 914-936, May 2024.
in Journal of Neurophysiology on 2024-05-16 05:59:50 UTC.
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Journal of Neurophysiology, Volume 131, Issue 5, Page 903-913, May 2024.
in Journal of Neurophysiology on 2024-05-16 05:59:49 UTC.
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Journal of Neurophysiology, Volume 131, Issue 5, Page 945-947, May 2024.
in Journal of Neurophysiology on 2024-05-16 05:59:47 UTC.
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Science, Volume 384, Issue 6697, Page 746-746, May 2024.
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Science, Volume 384, Issue 6697, Page 745-745, May 2024.
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Science, Volume 384, Issue 6697, Page 785-792, May 2024.
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Science, Volume 384, Issue 6697, Page 763-767, May 2024.
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Science, Volume 384, Issue 6697, Page 781-785, May 2024.
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Science, Volume 384, Issue 6697, Page 802-808, May 2024.
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Science, Volume 384, Issue 6697, Page 776-781, May 2024.
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Science, Volume 384, Issue 6697, Page 747-748, May 2024.
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Science, Volume 384, Issue 6697, Page 748-748, May 2024.
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Science, Volume 384, Issue 6697, Page 747-747, May 2024.
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Science, Volume 384, Issue 6697, Page 750-752, May 2024.
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A recent study by Hadler and colleagues uncovered a novel form of plasticity of gamma oscillations in an ex vivo hippocampal slice preparation which they term 'gamma potentiation'. We discuss the potential cellular mechanisms of this form of plasticity and its functional and translational implications.
in Trends in Neurosciences: In press on 2024-05-16 00:00:00 UTC.
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In a recent study, Ziak et al. employed precise sparse labeling and spatiotemporally controlled genetic manipulations to uncover novel regulators of axon branching of layer 2/3 mouse callosal projection neurons. The authors elucidated a cell-autonomous signaling pathway wherein glycogen synthase kinase 3β (GSK3β) phosphorylation of microtubule-associated protein 1B (MAP1B) restricts interstitial axon branching by modulating microtubule (MT) tyrosination status.
in Trends in Neurosciences: In press on 2024-05-16 00:00:00 UTC.
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(Neuron 94, 611–625.e1–e4; May 3, 2017)
in Neuron: In press on 2024-05-16 00:00:00 UTC.
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(Neuron 95, 955–970.e1–e4; August 16, 2017)
in Neuron: In press on 2024-05-16 00:00:00 UTC.
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Spyropoulos et al. show that attention modulates V1-V4 firing rates and gamma phase-locking via distinct feedforward and feedback pathways. Firing-rate modulation is strongest and earliest in Layers II/III of V4, consistent with feedback. Gamma phase-locking to feedforward V1 gamma is confined to fast-spiking interneurons in Layer IV of V4.
in Neuron: In press on 2024-05-16 00:00:00 UTC.
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Technologies for axon guidance for in vitro disease models and bottom up investigations are increasingly being used in neuroscience research. One of the most prevalent patterning methods is using polydimethylsiloxane (PDMS) microstructures due to compatibility with microscopy and electrophysiology which enables systematic tracking of axon development with precision and efficiency. Previous investigations of these guidance platforms have noted axons tend to follow edges and avoid sharp turns; however, the specific impact of spatial constraints remains only partially explored. We investigated the influence of microchannel width beyond a constriction point, as well as the number of available microchannels, on axon growth dynamics. Further, by manipulating the size of micron/submicron-sized PDMS tunnels we investigated the space restriction that prevents growth cone penetration showing that restrictions smaller than 350nm were sufficient to exclude axons. This research offers insights into the interplay of spatial constraints, axon development, and neural behavior. The findings are important for designing in vitro platforms and in vivo neural interfaces for both fundamental neuroscience and translational applications in rapidly evolving neural implant technologies.
in bioRxiv: Neuroscience on 2024-05-16 00:00:00 UTC.
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Emerging interests in the field of research related to diseases such as Alzheimers disease, Parkinsons disease, cognition, and other mental health-related disorders have prompted a need for a common method for the isolation of serum, CSF, and hippocampus. The hippocampus is responsible for learning and memory. It can be affected by various neurological and psychiatric disorders. However, the process of collecting samples such as CSF and hippocampal neurons is challenging, especially for small animals like rats. We have presented here a method for the isolation of serum, CSF, and hippocampal neurons that can be used for its downstream applications such as proteomics. We have used high-speed centrifugation instruments and density gradient centrifugation methods, which are easy to follow. Additionally, we have tested the proteins identified through mass spectrometry. Our method enables the study of proteins in serum, CSF, and neural cells for researching protein cross-talks and neurological disorder mechanisms.
in bioRxiv: Neuroscience on 2024-05-16 00:00:00 UTC.
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Accurate estimation of heading direction from optic flow is a crucial aspect of human spatial perception. Previous studies have shown that humans are typically biased in their estimates of heading directions, but the reported results are inconsistent. While some studies found that humans generally underestimate heading direction (central bias), others find the opposite, an overestimation of heading direction (peripheral bias). We conducted three psychophysical experiments showing that these conflicting findings do not reflect inherent differences in heading perception. Rather we found that they are caused by the different sizes of the response range that participants were allowed to utilize when reporting their estimates. Notably, we show that participants' heading estimates monotonically scale with the size of the response range, leading to underestimation for small and overestimation for large response ranges. Additionally, neither the speed profile of the optic flow pattern nor the response method (mouse vs. keyboard) significantly affected participants' estimates. Furthermore, we derived a Bayesian observer model to quantitatively account for participants' estimation behavior. The model assumes an efficient sensory encoding of heading direction according to the natural prior of freely behaving humans. In addition, the model incorporates a motor stage that linearly maps the percept to the reported estimate with a scaling factor that depends on the size of the response range. This perception-action model accurately predicts participants' estimates both in terms of mean and variance. Our findings underscore that human heading perception follows efficient Bayesian inference; differences in participants' reported estimates can be solely attributed to differences in linear mapping from percept to probe response.
in bioRxiv: Neuroscience on 2024-05-16 00:00:00 UTC.