bluuebunny/crossref_metadata_2025_split huggingface dataset:
Central desks as an approach for health governance in conflict settings – case studies from northwest Syria
Authors: Aref Maher Al , Zoubi Zedoun Al , Khalil Munzer Al , Abdulla Orwa Al , Ekzayez Abdulkarim 
Published: September 2022

AbstractBackgroundThe conflict in Syria affected severely the health sector; health infrastructure was damaged, the Damascus ministry of health withdrew from opposition held areas, health workers fled the country, and there has been always a shortage of funding and medical supplies. To address these needs, Syrian NGOs, INGOs, donors, and UN Agencies have been providing health interventions through humanitarian channels. However, many of these interventions were short termed, and there was no governance framework to guide the newly introduced parallel system, leaving it subject to individual organizations’ strategies and approaches.To counter these challenges, local communities and Syrian NGOs established new platforms to govern and coordinate certain aspects of the health sector. These platforms are called “central desks”, which are perceived to be independent and neutral structures and can coordinate services between all actors. Examples of these structures are Syrian Immunization Group (SIG), Health Information System (HIS), the Infection Protection and Control initiative (IPC), and the Referral System network.MethodsThe research was based on an institutional approach to governance as presented by (Abimbola et. Al, 2017) and (Baez-Carmago and Jacobs, 2011) of health governance. We have investigated the central desks across the main themes; governance inputs of these central desks, such as strategic vision and legitimacy; governance processes, such as accountability and transparency, and governance outcomes, such as effectiveness and efficiency. Further to intensive literature review, eight focus group discussion were conducted, average pf 12 participants. Key themes then were deducted and coded. The qualitative analysis was done using NVIVO 12 software.ConclusionCentral desks, that are not part of national ministries of health, are new innovative approaches that can increase the efficiency of health interventions in conflict settings. The detailed features of such desks should be context specific and locally informed and led.
“E Pluribus Unum”: Prospective acceptability benchmarking from the Contouring Collaborative for Consensus in Radiation Oncology (C3RO) Crowdsourced Initiative for Multi-Observer Segmentation
Authors: Lin Diana , Wahid Kareem A. , Nelms Benjamin E. , He Renjie , Naser Mohammed A. , Duke Simon , Sherer Michael V. , Christodouleas John P. , Mohamed Abdallah S. R. , Cislo Michael , Murphy James D. , Fuller Clifton D. , Gillespie Erin F. 
Published: September 2022

AbstractOBJECTIVEContouring Collaborative for Consensus in Radiation Oncology (C3RO) is a crowdsourced challenge engaging radiation oncologists across various expertise levels in segmentation. A challenge in artificial intelligence (AI) development is the paucity of multi-expert datasets; consequently, we sought to characterize whether aggregate segmentations generated from multiple non-experts could meet or exceed recognized expert agreement.MATERIALS AND METHODSParticipants who contoured ≥1 region of interest (ROI) for the breast, sarcoma, head and neck (H&N), gynecologic (GYN), or gastrointestinal (GI) challenge were identified as a non-expert or recognized expert. Cohort-specific ROIs were combined into single simultaneous truth and performance level estimation (STAPLE) consensus segmentations. STAPLEnon-expert ROIs were evaluated against STAPLEexpert contours using Dice Similarity Coefficient (DSC). The expert interobserver DSC (IODSCexpert) was calculated as an acceptability threshold between STAPLEnon-expert and STAPLEexpert. To determine the number of non-experts required to match the IODSCexpert for each ROI, a single consensus contour was generated using variable numbers of non-experts and then compared to the IODSCexpert.RESULTSFor all cases, the DSC for STAPLEnon-expert versus STAPLEexpert were higher than comparator expert IODSCexpert for most ROIs. The minimum number of non-expert segmentations needed for a consensus ROI to achieve IODSCexpert acceptability criteria ranged between 2-4 for breast, 3-5 for sarcoma, 3-5 for H&N, 3-5 for GYN ROIs, and 3 for GI ROIs.DISCUSSION AND CONCLUSIONMultiple non-expert-generated consensus ROIs met or exceeded expert-derived acceptability thresholds. 5 non-experts could potentially generate consensus segmentations for most ROIs with performance approximating experts, suggesting non-expert segmentations as feasible cost-effective AI inputs.
Zymosan-induced leukocyte and cytokine changes in pigs: a new model for streamlined drug testing against severe COVID-19
Authors: Kökény Gábor , Bakos Tamás , Barta Bálint András , Nagy Georgina Viktória , Mészáros Tamás , Kozma Gergely T. , Szabó András , Szebeni János , Merkely Béla , Radovits Tamás 
Published: September 2022

AbstractInjection of 0.1 mg/kg zymosan in pigs i.v. elicited transient hemodynamic disturbance within minutes, without major blood cell changes. In contrast, infusion of 1 mg/kg zymosan triggered maximal pulmonary hypertension with tachycardia, lasting for 30 min. This change was followed by a transient granulopenia with a trough at 1 h, and then, up to about 6 h, a major granulocytosis, resulting in a 3-4-fold increase of neutrophil-to-lymphocyte ratio (NLR). In parallel with the changes in WBC differential, qRT-PCR and ELISA analyses showed increased transcription and/or release of inflammatory cytokines and chemokines into blood, including IL-6, TNF-α, CCL-2, CXCL-10, and IL-1RA. The expression of IL-6 peaked at already 1.5-2.5 h, and we observed significant correlation between lymphopenia and IL-6 gene expression. While these changes are consistent with zymosan’s known stimulatory effect on both the humoral and cellular arms of the innate immune system, what gives novel clinical relevance to the co-manifestation of above hemodynamic, hematological, and immune changes is that they represent independent bad prognostic indicators in terminal COVID-19 and other diseases involving cytokine storm. Thus, within a 6 h experiment, the model enables consecutive reproduction of a symptom triad that is characteristic of late-stage COVID-19. Given the limitations of modeling cytokine storm in animals and effectively treating severe COVID-19, the presented relatively simple large animal model may advance the R&D of drugs against these conditions. One of these disease markers (NLR), obtained from a routine laboratory endpoint (WBC differential), may also enable streamlining the model for high throughput drug screening against innate immune overstimulation.
A Complete Set of Equations for a Computational Model of Electrolyte and Water Transport along the Nephrons in a Mammalian Kidney
Authors: Layton Anita T. 
Published: September 2022

AbstractTo investigate kidney under different physiological and pharmacological conditions, we have developed and applied computational models of electrolyte and water transport along nephrons in a kidney. The models predict spredict luminal fluid flow, hydrostatic pressure, membrane potential, luminal and cytosolic solute concentrations, and transcellular and paracellular fluxes through transporters and channels. The complete set of model equations are presented here.
Stress and Coping Strategies among Medical Students in Dubai, United Arab Emirates, in 2020: A Cross-Sectional Study
Authors: Boushehri Yas Kaveh , Jeyaseelan Lakshmanan , Sultan Meshal A. 
Published: September 2022

ABSTRACTStudies across the world, have revealed elevated levels of stress among medical students. The rate of significant stress is 55% higher among healthcare professionals in comparison to the general population. This level of stress may lead to higher rates of burnout, depression, and functional impairment. This study aims to investigate the stress levels among medical students in Dubai and also to assess their coping strategies. The total number of participants in this study was 97. Rates of high stress levels as per the Perceived Stress Scale (PSS-10) was found to be higher among year 1 to year 3 medical students (43.6%), in comparison to year 4 and year 5 medical students (7.7%). The Brief-COPE inventory was used in this study and found that among medical students the mean score for a Problem Focused coping style was 22 out of 32 (medium to high range). Future research that evaluates a more comprehensive investigation into the psychological impact of stress and also exploration of effective strategies to enhance coping with stress is highly warranted.
Inferential Eye Movement Control while Following Dynamic Gaze
Authors: Han Nicole X. , Eckstein Miguel P. 
Published: September 2022

ABSTRACTAttending to other people’s gaze is evolutionary important to make inferences about intentions and actions. Gaze influences covert attention and triggers eye movements. However, we know little about how the brain controls the fine-grain dynamics of eye movements during gaze following. Observers followed people’s gaze shifts in videos during search and we related the observer eye movement dynamics to the timecourse of gazer head movements extracted by a deep neural network. We show that the observers’ brains use information in the visual periphery to execute predictive saccades that anticipate the information in the gazer’s head direction by 190-350 ms. The brain simultaneously monitors moment-to-moment changes in the gazer’s head velocity to dynamically alter eye movements and re-fixate the gazer (reverse saccades) when the head accelerates before the initiation of the first forward gaze-following saccade. Using saccade-contingent manipulations of the videos, we experimentally show that the reverse saccades are planned concurrently with the first forward gaze-following saccade and have a functional role in reducing subsequent errors fixating on the gaze goal. Together, our findings characterize the inferential and functional nature of the fine-grain eye movement dynamics of social attention.
clrDV: A differential variability test for RNA-Seq data based on the skew-normal distribution
Authors: Li Hongxiang , Khang Tsung Fei 
Published: September 2022

SummaryGenes that show differential variability between conditions are important for complementing a systems biology understanding of the molecular players involved in a biological process. Under the dominant paradigm for modeling RNA-Seq gene counts using the negative binomial model, tests of differential variability are challenging to develop, owing to dependence of the variance on the mean. The limited availability of methods for detecting genes with differential variability means that researchers often omit differential variability as an analytical step in RNA-Seq data analysis. Here, we describe clrDV, a statistical method for detecting genes that show differential variability between two populations. clrDV is based on a compositional data analysis framework. We present the skew-normal distribution for modeling gene-wise null distribution of centered log-ratio transformation of compositional RNA-seq data. Simulation results show that clrDV has false discovery rate and Type II error that are on par with or superior to existing methodologies. In addition, its run time is faster than the closest competitor’s, and remains relatively constant for increasing sample size per group. Analysis of a large neurodegenerative disease RNA-Seq dataset using clrDV recovers multiple gene candidates that have been reported to be associated with Alzheimer’s disease. Additionally, we find that the majority of genes with differential variability have smaller relative gene expression variance in the Alzheimer’s disease population compared to the control population.
Mitf is a Schwann Cell Sensor of Axonal Integrity that Drives Nerve Repair
Authors: Daboussi Lydia , Costaguta Giancarlo , Gullo Miriam , Jasinski Nicole , Pessino Veronica , O’Leary Brendan , Lettieri Karen , Driscoll Shawn , Pfaff Samuel L. 
Published: September 2022

SummarySchwann cells respond to acute axon damage by transiently transdifferentiating into specialized repair cells that restore sensorimotor function. However, the molecular systems controlling repair cell formation and function are not well defined and consequently it is unclear whether this form of cellular plasticity has a role in peripheral neuropathies. Here we identify Mitf as a transcriptional sensor of axon damage under the control of Nrg-ErbB-PI3K-PI5K-mTorc2 signaling. Mitf regulates a core transcriptional program for generating functional repair Schwann cells following injury and during peripheral neuropathies caused by CMT4J and CMT4D. In the absence of Mitf, core genes for epithelial-to-mesenchymal transition, metabolism and dedifferentiation are misexpressed and nerve repair is disrupted. Taken together, our findings demonstrate that Schwann cells monitor axonal health using a phosphoinositide signaling system that controls Mitf, which is critical for activating cellular plasticity and counteracting neural disease.HighlightsMitf-induced Schwann cell plasticity is triggered by peripheral neuropathy.Nrg-ErbB signaling activates Mitf via cytoplasmic-to-nuclear translocation.Mitf restores sensorimotor function following axonal breakdown.Mitf regulates a core repair program across both injury and neurodegeneration.
Comparison of gene clustering criteria reveals intrinsic uncertainty in pangenome analyses
Authors: Manzano-Morales Saioa , Liu Yang , González-Bodí Sara , Huerta-Cepas Jaime , Iranzo Jaime 
Published: September 2022

AbstractBackgroundA key step for comparative genomics is to group open reading frames into functionally and evolutionarily meaningful gene clusters. Gene clustering is complicated by intraspecific duplications and horizontal gene transfers, that are frequent in prokaryotes. In consequence, gene clustering methods must deal with a trade-off between identifying vertically transmitted representatives of multi-copy gene families (recognizable by synteny conservation) and retrieving complete sets of species-level orthologs. We studied the implications of adopting homology, orthology, or synteny conservation as formal criteria for gene clustering by performing comparative analyses of 125 prokaryotic pangenomes.ResultsClustering criteria affect pangenome functional characterization, core genome inference, and reconstruction of ancestral gene content to different extents. Species-wise estimates of pangenome and core genome sizes change by the same factor when using different clustering criteria, which allows for robust cross-species comparisons regardless of the clustering criterion. However, cross-species comparisons of genome plasticity and functional profiles are substantially affected by inconsistencies among clustering criteria. Such inconsistencies are driven not only by mobile genetic elements, but also by genes involved in defense, secondary metabolism, and other accessory functions. In some pangenome features, the variability attributed to methodological inconsistencies can even exceed the effect sizes of ecological and phylogenetic variables.ConclusionsChoosing an appropriate criterion for gene clustering is critical to conduct unbiased pangenome analyses. We provide practical guidelines to choose the right method depending on the research goals and the quality of genome assemblies, and a benchmarking dataset to assess the robustness and reproducibility of future comparative studies.
Human-like Modulation Sensitivity Emerging through Optimization to Natural Sound Recognition
Authors: Koumura Takuya , Terashima Hiroki , Furukawa Shigeto 
Published: September 2022

AbstractNatural sounds contain rich patterns of amplitude modulation (AM), which is one of the essential sound dimensions for hearing perception. The sensitivity of human hearing to AM measured by psychophysics takes diverse forms, from low-pass to high-pass, depending on the experimental conditions. Here, we address with a single framework the questions of why such patterns of AM sensitivity have emerged in the human auditory system and how they are realized by our neural mechanisms. Assuming that optimization for natural sound recognition has taken place during human evolution and development, we examined its effect on the formation of AM sensitivity by optimizing a computational model, specifically, a multi-layer (or deep) neural network, for natural sound recognition and simulating psychophysical experiments in which the model’s AM sensitivity was measured. Relatively higher layers in the optimized model exhibited qualitatively and quantitatively similar AM sensitivity to that of humans, even though the model was not designed to reproduce human-like AM sensitivity. The similarity of the model’s AM sensitivity to humans’ correlated with its sound recognition accuracy. Optimization of the model to degraded sounds revealed the necessity of natural AM patterns for the emergence of human-like AM sensitivity. Consistent results were observed from optimizations to two different types of natural sound. Moreover, simulated neurophysiological experiments on the same model revealed a correspondence between the model layers and the auditory brain regions that is based on the similarity of their neural AM tunings. The layers in which human-like psychophysical AM sensitivity emerged exhibited substantial neurophysiological similarity with the auditory midbrain and higher regions. These results suggest that the behavioral AM sensitivity of human hearing has emerged as a result of optimization for natural-sound recognition in the course of our evolution and/or development and that it is based on a stimulus representation encoded in the neural firing rates in the auditory midbrain and higher regions.
Amyloid-beta biomarkers in Braak stages and their predictive relationships with cognitive impairment: Support vector machine and deep learning approaches
Authors: Taha Ahmed , Soni Bhavin , Thakuri Deepa S. , Ritter Erin , Bhattarai Puskar , Chand Ganesh B. 
Published: September 2022

ABSTRACTAmyloid-beta (Aβ) and tau tangles are hallmarks of Alzheimer’s disease. Aβ distributions in the tau-defined Braak staging regions and their multivariate predictive relationships with mild cognitive impairment (MCI) are not known. In this study, we used PiB PET data from 60 participants (33 with MCI and 27 healthy controls (HC)), quantified Aβ as distribution volume ratio (DVR) in Braak regions, and compared between MCI and controls to test the hypothesis that DVR alters with declining cognition. We found elevated DVR in participants with MCI, especially in the spatial distribution of Braak stages III-IV and V-VII, while an alteration in Braak stage I-II was near the statistical significance. DVR markers correlated with cognitive status, especially in Braak stages III-IV and VI-V. To evaluate whether these markers are predictive of cognitive dysfunction, we designed support vector machine and artificial neural network models. These methods showed predictive multivariate relationships between Aβ makers of Braak regions and cognitive impairment. Overall, these results highlight the importance of computer-aided research efforts for understanding AD pathophysiology.
The genetic basis for adaptation in giant sea anemones to their symbiosis with anemonefish and Symbiodiniaceae
Authors: Barua Agneesh , Kashimoto Rio , Khalturin Konstantin , Satoh Noriyuki , Laudet Vincent 
Published: September 2022

AbstractSea anemones in the order Anthozoa play an integral part in marine ecosystems by providing refuge and habitat for various organisms. Despite this, much of their molecular ecology remains elusive. Sea anemones can nurture numerous symbiotic relationships; the most iconic being the one between giant sea anemones and anemonefish. However, the genes and biological processes associated with this symbiosis in the sea anemones in unknown. Additionally, it is unclear how genes can mediate interactions between sea anemones, anemonefish, and symbionts from the algal family Symbiodiniaceae. Here we compared the gene expression profiles of tentacles from several cnidarians to uncover the genetic basis for adaptations in giant sea anemones to their symbiosis with anemonefish and Symbiodiniaceae. We found that tentacle transcriptomes of cnidarians are highly diverse, with closely related species having more similar expression patterns. However, despite an overall high correlation between gene expression and phylogeny, the giant sea anemones showed distinct expression patterns. The giant sea anemones had gene co-expression clusters enriched for processes involved in nutrient exchange and metabolism. These genes were not only differentially expressed, but also experienced evolutionary shifts in expression in giant sea anemones. Using a phylogenetic multilevel model, we found that Symbiodiniaceae and anemonefish significantly affect gene expression in giant sea anemone tentacles. By characterizing gene expression patterns, we identify genes and biological processes that provide evidence for the cross-talk between Symbiodiniaceae, anemonefish, and giant sea anemones. Our study demonstrates how integrated biological processes can lead to the evolution of a successful multi-organism interaction.
Chitinase-3-like 1 regulates TH2 cells, TFHcells and IgE following helminth infection
Authors: Curtiss Miranda L. , Rosenberg Alexander F. , Scharer Christopher D. , Mousseau Betty , Ballesteros Benavides Natalia A. , Bradley John E. , León Beatriz , Steele Chad , Randall Troy D. , Lund Frances E. 
Published: September 2022

AbstractData from patient cohorts and mouse models of atopic dermatitis, food allergy and asthma strongly support a role for the chitinase-like protein ChI3L1 in allergic disease. To address whether CHI3L1 also contributes to TH2 responses following nematode infection, we infectedChi3l1-/-mice withHeligmosomoides polygyrus(Hp) and analyzed T cell responses. Not surprisingly, we observed impaired TH2 responses inHp-infectedChi3l1-/-mice. However, we also found that T cell intrinsic expression ofChi3l1was required for ICOS upregulation following activation of naïve CD4 T cells and was necessary for the development of the IL-4+TFHsubset, which supports germinal center (GC) B cell reactions and IgE responses. The requirement forChi3l1in TFHand IgE responses was also seen following alum-adjuvanted vaccination. While Chi3l1 was critical for IgE humoral responses it was not required for vaccine or infection induced IgG1 responses. These results suggest thatChi3l1specifically modulates IgE responses that are highly dependent on help from IL-4-producing TFHcells.