bluuebunny/crossref_metadata_2025_split huggingface dataset:
toxCSM: comprehensive prediction of small molecule toxicity profiles
Authors: de Sá Alex G C , Long Yangyang , Portelli Stephanie , Pires Douglas E V , Ascher David B 
Published: August 2022

Abstract
Drug discovery is a lengthy, costly and high-risk endeavour that is further convoluted by high attrition rates in later development stages. Toxicity has been one of the main causes of failure during clinical trials, increasing drug development time and costs. To facilitate early identification and optimisation of toxicity profiles, several computational tools emerged aiming at improving success rates by timely pre-screening drug candidates. Despite these efforts, there is an increasing demand for platforms capable of assessing both environmental as well as human-based toxicity properties at large scale. Here, we present toxCSM, a comprehensive computational platform for the study and optimisation of toxicity profiles of small molecules. toxCSM leverages on the well-established concepts of graph-based signatures, molecular descriptors and similarity scores to develop 36 models for predicting a range of toxicity properties, which can assist in developing safer drugs and agrochemicals. toxCSM achieved an Area Under the Receiver Operating Characteristic (ROC) Curve (AUC) of up to 0.99 and Pearson’s correlation coefficients of up to 0.94 on 10-fold cross-validation, with comparable performance on blind test sets, outperforming all alternative methods. toxCSM is freely available as a user-friendly web server and API at http://biosig.lab.uq.edu.au/toxcsm.
Profiling prediction of nuclear receptor modulators with multi-task deep learning methods: toward the virtual screening
Authors: Wang Jiye , Lou Chaofeng , Liu Guixia , Li Weihua , Wu Zengrui , Tang Yun 
Published: August 2022

Abstract
Nuclear receptors (NRs) are ligand-activated transcription factors, which constitute one of the most important targets for drug discovery. Current computational strategies mainly focus on a single target, and the transfer of learned knowledge among NRs was not considered yet. Herein we proposed a novel computational framework named NR-Profiler for prediction of potential NR modulators with high affinity and specificity. First, we built a comprehensive NR data set including 42 684 interactions to connect 42 NRs and 31 033 compounds. Then, we used multi-task deep neural network and multi-task graph convolutional neural network architectures to construct multi-task multi-classification models. To improve the predictive capability and robustness, we built a consensus model with an area under the receiver operating characteristic curve (AUC) = 0.883. Compared with conventional machine learning and structure-based approaches, the consensus model showed better performance in external validation. Using this consensus model, we demonstrated the practical value of NR-Profiler in virtual screening for NRs. In addition, we designed a selectivity score to quantitatively measure the specificity of NR modulators. Finally, we developed a freely available standalone software for users to make profiling predictions for their compounds of interest. In summary, our NR-Profiler provides a useful tool for NR-profiling prediction and is expected to facilitate NR-based drug discovery.
YAMACS: a graphical interface for GROMACS
Authors: Sarkar Arkadeep , Santoro Jacopo , Di Biasi Luigi , Marrafino Francesco , Piotto Stefano 
Published: August 2022

AbstractSummaryA graphical user interface for the GROMACS program has been developed as plugins for YASARA molecular graphics suite. The most significant GROMACS methods can be run entirely via a windowed menu system, and the results are shown on screen in real time.Availability and implementationYAMACS is written in Python and is freely available for download at https://github.com/YAMACS-SML/YAMACS and is supported on Linux. It has been released under GPL-3.0 license.Supplementary informationSupplementary data are available at Bioinformatics online.
Dynamic changes in spatial representation within the posterior parietal cortex in response to visuomotor adaptation
Authors: Schintu S , Kravitz D J , Silson E H , Cunningham C A , Wassermann E M , Shomstein S 
Published: August 2022

AbstractRecent studies used functional magnetic resonance imaging (fMRI) population receptive field (pRF) mapping to demonstrate that retinotopic organization extends from the primary visual cortex to ventral and dorsal visual pathways, by quantifying visual field maps, receptive field size, and laterality throughout multiple areas. Visuospatial representation in the posterior parietal cortex (PPC) is modulated by attentional deployment, raising the question of whether spatial representation in the PPC is dynamic and flexible, and whether this flexibility contributes to visuospatial learning. To answer this question, changes in spatial representation within the PPC and early visual cortex were recorded with pRF mapping before and after prism adaptation (PA)—a well-established visuomotor technique that modulates visuospatial attention according to the direction of the visual displacement. As predicted, results showed that adaptation to left-shifting prisms increases pRF size in left PPC, while leaving space representation in the early visual cortex unchanged. This is the first evidence that PA drives a dynamic reorganization of response profiles in the PPC. These findings show that spatial representations in the PPC not only reflect changes driven by attentional deployment but dynamically change in response to modulation of external factors such as manipulation of the visuospatial input during visuomotor adaptation.
Obesity is associated with decreased gray matter volume in children: a longitudinal study
Authors: Jiang Fukun , Li Guanya , Ji Weibin , Zhang Yaqi , Wu Feifei , Hu Yang , Zhang Wenchao , Manza Peter , Tomasi Dardo , Volkow Nora D , Gao Xinbo , Wang Gene-Jack , Zhang Yi 
Published: August 2022

AbstractChildhood obesity has become a global health problem. Previous studies showed that childhood obesity is associated with brain structural differences relative to controls. However, few studies have been performed with longitudinal evaluations of brain structural developmental trajectories in childhood obesity. We employed voxel-based morphometry (VBM) analysis to assess gray matter (GM) volume at baseline and 2-year follow-up in 258 obese children (OB) and 265 normal weight children (NW), recruited as part of the National Institutes of Health Adolescent Brain and Cognitive Development study. Significant group × time effects on GM volume were observed in the prefrontal lobe, thalamus, right precentral gyrus, caudate, and parahippocampal gyrus/amygdala. OB compared with NW had greater reductions in GM volume in these regions over the 2-year period. Body mass index (BMI) was negatively correlated with GM volume in prefrontal lobe and with matrix reasoning ability at baseline and 2-year follow-up. In OB, Picture Test was positively correlated with GM volume in the left orbital region of the inferior frontal gyrus (OFCinf_L) at baseline and was negatively correlated with reductions in OFCinf_L volume (2-year follow-up vs. baseline). These findings indicate that childhood obesity is associated with GM volume reduction in regions involved with reward evaluation, executive function, and cognitive performance.
Pseudohypobicarbonatemia in a patient with amyloidosis
Authors: Bukhari Marvi , Boyd-Shiwarski Cary , Abramovitz Blaise 
Published: August 2022

ABSTRACT
We report a case of a patient who had critically low serum bicarbonate (HCO3−) levels ranging from 8 to 11 mmol/L on repeated venous measurements using an enzymatic/photometric assay. This prompted hospitalization and treatment with intravenous sodium bicarbonate (NaHCO3) followed by oral NaHCO3. He was evaluated for potential causes of high anion gap metabolic acidosis without any etiology found. He continued to have low serum HCO3− levels despite maintenance oral NaHCO3 therapy and was referred for a second opinion where further laboratory work was pursued. An arterial blood gas was obtained, which revealed normal whole blood pH and HCO3− levels. A different enzymatic/photometric assay revealed a normal serum HCO3− level at 21 mmol/L. Additional workup revealed paraproteinemia, which was thought to interfere with the enzymatic process by which his serum HCO3− was measured, resulting in erroneous values.
Sequential motifs in observed walks
Authors: LaRock Timothy , Scholtes Ingo , Eliassi-Rad Tina 
Published: August 2022

Abstract
The structure of complex networks can be characterized by counting and analysing network motifs. Motifs are small graph structures that occur repeatedly in a network, such as triangles or chains. Recent work has generalized motifs to temporal and dynamic network data. However, existing techniques do not generalize to sequential or trajectory data, which represent entities moving through the nodes of a network, such as passengers moving through transportation networks. The unit of observation in these data is fundamentally different since we analyse observations of trajectories (e.g. a trip from airport A to airport C through airport B), rather than independent observations of edges or snapshots of graphs over time. In this work, we define sequential motifs in trajectory data, which are small, directed and sequence-ordered graphs corresponding to patterns in observed sequences. We draw a connection between the counting and analysis of sequential motifs and Higher-Order Network (HON) models. We show that by mapping edges of a HON, specifically a $k$th-order DeBruijn graph, to sequential motifs, we can count and evaluate their importance in observed data. We test our methodology with two datasets: (1) passengers navigating an airport network and (2) people navigating the Wikipedia article network. We find that the most prevalent and important sequential motifs correspond to intuitive patterns of traversal in the real systems and show empirically that the heterogeneity of edge weights in an observed higher-order DeBruijn graph has implications for the distributions of sequential motifs we expect to see across our null models.
Body mass index in young men in Switzerland after the national shutdowns during the COVID-19 pandemic: results from a cross-sectional monitoring study at the population level since 2010
Authors: Meili Samuel , Brabec Marek , Rühli Frank , Buehrer Thomas W , Gültekin Nejla , Stanga Zeno , Bender Nicole , Staub Kaspar , Reber Emilie 
Published: August 2022

Abstract

Background
Owing to the coronavirus disease pandemic, the Swiss goverment imposed a shutdown twice in 2020, which may have changed diet and physical activity. Regarding the question of weight change during the pandemic, little information based on measured weight data is available. We aimed to investigate whether the body mass indices (BMIs) of young Swiss men after the two shutdowns in spring and fall 2020 differed from those of young men examined before the shutdowns.

Methods
We analysed young Swiss men’s BMIs taken during mandatory recruitment for the Swiss Armed Forces at the cross-sectional (not individual longitudinal) monitoring level and across weeks of conscription between January 2010 and July 2021 (n = 373 016). These data allow for continuous health monitoring of young men at almost the population level (coverage, &gt;90%). For statistical modelling, we used the generalized additive model (GAM) framework.

Results
We showed that the BMIs of the conscripts examined in the 15 weeks after the two shutdowns in spring and autumn 2020 were not or only slightly different from their baseline values. Sensitivity analyses revealed that this conclusion also holds if the BMI distribution or prevalence of excess weight is assessed. The GAM further showed the significant effects of individual and area-based measures of socioeconomic position and age on BMI.

Conclusion
Our results suggest that lifestyle changes during the pandemic in young men might have been too modest to be reflected in body weight. However, longitudinal data and/or data on women, children, or the elderly may lead to different conclusions.
Implementing a home-based virtual hypertension programme—a pilot feasibility study
Authors: Gupta Aditi , Ellis Shellie D , Burkhardt Crystal , Young Kate , Mazzotti Diego R , Mahnken Jonathan , Abu-el-rub Noor , Chandaka Sravani , Comfort Branden , Shanks Denton , Woodward Jennifer , Unrein Amber , Anderson Heidi , Loucks Jennifer , Song Xing , Waitman Lemuel R , Burns Jeffrey M 
Published: August 2022

AbstractIntroductionImplementing a health system-based hypertension programme may lower blood pressure (BP).MethodsWe performed a randomized, controlled pilot study to assess feasibility, acceptability, and safety of a home-based virtual hypertension programme integrating evidence-based strategies to overcome current barriers to BP control. Trained clinical pharmacists staffed the virtual collaborative care clinic (vCCC) to remotely manage hypertension using a BP dashboard and phone “visits” to monitor BP, adherence, side effects of medications, and prescribe anti-hypertensives. Patients with uncontrolled hypertension were identified via electronic health records. Enrolled patients were randomized to either vCCC or usual care for 3 months. We assessed patients’ home BP monitoring behaviour, and patients’, physicians’, and pharmacists’ perspectives on feasibility and acceptability of individual programme components.ResultsThirty-one patients (vCCC = 17, usual care = 14) from six physician clinics completed the pilot study. After 3 months, average BP decreased in the vCCC arm (P = 0.01), but not in the control arm (P = 0.45). The vCCC participants measured BP more (9.9 vs. 1.2 per week, P &lt; 0.001). There were no intervention-related adverse events. Participating physicians (n = 6), pharmacists (n = 5), and patients (n = 31) rated all programme components with average scores of &gt;4.0, a pre-specified benchmark. Nine adaptations in vCCC design and delivery were made based on potential barriers to implementing the programme and suggestions.ConclusionA home-based virtual hypertension programme using team-based care, technology, and a logical integration of evidence-based strategies is safe, acceptable, and feasible to intended users. These pilot data support studies to assess the effectiveness of this programme at a larger scale.
One-step PCR amplicon sequencing libraries perform better than two-step when assessing soil microbial diversity and community profiles
Authors: Finn Damien R , Samad Md Sainur , Tebbe Christoph C 
Published: August 2022

ABSTRACTDespite adoption of high-throughput sequencing of PCR-amplified microbial taxonomic markers for ecological analyses, distinct approaches for preparing amplicon libraries exist. One approach utilises long fusion primers and a single PCR (one-step) while another utilises shorter primers in a first reaction, before transferring diluted amplicons to a second reaction for barcode index incorporation (two-step). We investigated whether transferring diluted amplicons risked creating artificially simplified, poorly diverse communities. In soils from three sites with paired cropland and forest, one-step yielded higher alpha-diversity indices, including detection of two–four times more unique taxa. Modelling expected taxa per sequence observation predicted that one-step reaches full coverage by 104 sequences per sample while two-step needs 105–109. Comparisons of rank abundance demonstrated that two-step covered only 38%–69% of distributions. Beta-diversity showed better separation of communities in response to land use change under one-step, although both approaches showed a significant effect. Driving differences was underestimation of relatively minor taxa with the two-step procedure. These taxa were low in abundance, yet play important roles in carbon cycling, secondary metabolite production, anaerobic metabolism, and bacterial predation. We conclude that one-step amplicon libraries are advisable for studies focussed on diversity or relatively minor yet functionally important taxa.
The implication of Sortase E in the morphology and physiology of Corynebacterium glutamicum
Authors: Aliyath Susmitha , Nampoothiri Kesavan Madhavan 
Published: August 2022

ABSTRACT
In this study, we analyzed the srtE gene from Corynebacterium glutamicum ATCC 13032, which codes for class E sortase, a transpeptidase involved in attaching surface proteins to the cell wall peptidoglycan. The surface proteins contain an N-terminal leader sequence and a C-terminal sorting signal which consist of a LAXTG motif, a transmembrane region, and a few positively charged amino acids. Sortase E deletion or its overexpression alters the attachment of the surface proteins to the cell wall peptidoglycan; however, the effects on morphology and bacterial physiology have not been studied. Thus, we constructed three C. glutamicum derivatives such as srtE deletion mutant, complemented and overexpressed strains to monitor the possible impact of the gene on cell growth, morphology, and physiological changes. Interestingly, deletion of the gene did not show any change in growth or morphology in C. glutamicum but showed a decrease in cell surface hydrophobicity and heat stress. However, the cells overexpressing the protein not only showed elongated cell morphology and a reduction in hydrophobicity when compared to wild-type and complemented strain, but also showed an increased sensitivity to heat. These results suggest that C. glutamicum sortase E deletion or overexpression causes sorting intermediates to accumulate, altering cellular morphology and physiology and adversely impacting the membrane integrity.
The Gallus gallus RJF reference genome reveals an MHCY haplotype organized in gene blocks that contain 107 loci including 45 specialized, polymorphic MHC class I loci, 41 C-type lectin-like loci, and other loci amid hundreds of transposable elements
Authors: Goto Ronald M , Warden Charles D , Shiina Takashi , Hosomichi Kazuyoshi , Zhang Jibin , Kang Tae Hyuk , Wu Xiwei , Glass Marla C , Delany Mary E , Miller Marcia M 
Published: August 2022

Abstract
MHCY is a second major histocompatibility complex-like gene region in chickens originally identified by the presence of major histocompatibility complex class I-like and class II-like gene sequences. Up to now, the MHCY gene region has been poorly represented in genomic sequence data. A high density of repetitive sequence and multiple members of several gene families prevented the accurate assembly of short-read sequence data for MHCY. Identified here by single-molecule real-time sequencing sequencing of BAC clones for the Gallus gallus Red Jungle Fowl reference genome are 107 MHCY region genes (45 major histocompatibility complex class I-like, 41 c-type-lectin-like, 8 major histocompatibility complex class IIβ, 8 LENG9-like, 4 zinc finger protein loci, and a single only zinc finger-like locus) located amid hundreds of retroelements within 4 contigs representing the region. Sequences obtained for nearby ribosomal RNA genes have allowed MHCY to be precisely mapped with respect to the nucleolar organizer region. Gene sequences provide insights into the unusual structure of the MHCY class I molecules. The MHCY class I loci are polymorphic and group into 22 types based on predicted amino acid sequences. Some MHCY class I loci are full-length major histocompatibility complex class I genes. Others with altered gene structure are considered gene candidates. The amino acid side chains at many of the polymorphic positions in MHCY class I are directed away rather than into the antigen-binding groove as is typical of peptide-binding major histocompatibility complex class I molecules. Identical and nearly identical blocks of genomic sequence contribute to the observed multiplicity of identical MHCY genes and the large size (&gt;639 kb) of the Red Jungle Fowl MHCY haplotype. Multiple points of hybridization observed in fluorescence in situ hybridization suggest that the Red Jungle Fowl MHCY haplotype is made up of linked, but physically separated genomic segments. The unusual gene content, the evidence of highly similar duplicated segments, and additional evidence of variation in haplotype size distinguish polymorphic MHCY from classical polymorphic major histocompatibility complex regions.
Heterogeneity in viral populations increases the rate of deleterious mutation accumulation
Authors: Allman Brent , Koelle Katia , Weissman Daniel 
Published: August 2022

Abstract
RNA viruses have high mutation rates, with the majority of mutations being deleterious. We examine patterns of deleterious mutation accumulation over multiple rounds of viral replication, with a focus on how cellular coinfection and heterogeneity in viral output affect these patterns. Specifically, using agent-based intercellular simulations we find, in agreement with previous studies, that coinfection of cells by viruses relaxes the strength of purifying selection and thereby increases the rate of deleterious mutation accumulation. We further find that cellular heterogeneity in viral output exacerbates the rate of deleterious mutation accumulation, regardless of whether this heterogeneity in viral output is stochastic or is due to variation in the cellular multiplicity of infection. These results highlight the need to consider the unique life histories of viruses and their population structure to better understand observed patterns of viral evolution.
Stress granule assemblyin vivois deficient in the CNS of mutant TDP-43 ALS mice
Authors: Dubinski Alicia , Gagné Myriam , Peyrard Sarah , Gordon David , Talbot Kevin , Vande Velde Christine 
Published: August 2022

AbstractResponding effectively to external stress is crucial for neurons. Defective stress granule dynamics has been hypothesized as one of the pathways that renders motor neurons in amyotrophic lateral sclerosis (ALS) more prone to early death. Specifically, it is thought that stress granules seed the cytoplasmic TDP-43 inclusions that are observed in the neurons of most ALS patients, as well as ~50% of all frontotemporal dementia (FTD) patients. In this study, we tested this hypothesis in an intact mammalian nervous system. We established an in vivo heat stress paradigm in mice that effectively triggers the eIF2α pathway and the formation of stress granules in the CNS. In non-transgenic mice, we report an age-dependent decline in the formation of heat-induced stress granules, with 18-month-old animals showing a significant impairment. Furthermore, although neuronal stress granules were robustly observed in non-transgenic mice and SOD1G93A mice, they were largely absent in age-matched TDP-43M337V animals. The observed defect in stress granule formation in TDP-43M337V mice correlated with deficits in expression of key protein components typically required for phase separation. Lastly, while TDP-43 was not localized to stress granules, we observed complete nuclear depletion of TDP-43 in a subset of neurons, with the highest proportion being in the TDP-43M337V mice. Overall, our results indicate that mutant TDP-43 expression is associated with defective stress granule assembly and increased TDP-43 nuclear depletion in the mammalian nervous system, which could be relevant to ALS/FTD pathogenesis.