bluuebunny/crossref_metadata_2025_split huggingface dataset:
A Digital Protein Microarray for COVID-19 Cytokine Storm Monitoring
Authors: Song Yujing , Ye Yuxuan , Su Shiuan-Haur , Stephens Andrew , Cai Tao , Chung Meng-Ting , Han Meilan , Newstead Michael W. , Frame David , Singer Benjamin H. , Kurabayashi Katsuo 
Published: June 2020

AbstractDespite widespread concern for cytokine storms leading to severe morbidity in COVID-19, rapid cytokine assays are not routinely available for monitoring critically ill patients. We report the clinical application of a machine learning-based digital protein microarray platform for rapid multiplex quantification of cytokines from critically ill COVID-19 patients admitted to the intensive care unit (ICU) at the University of Michigan Hospital. The platform comprises two low-cost modules: (i) a semi-automated fluidic dispensing/mixing module that can be operated inside a biosafety cabinet to minimize the exposure of technician to the virus infection and (ii) a 12-12-15 inch compact fluorescence optical scanner for the potential near-bedside readout. The platform enabled daily cytokine analysis in clinical practice with high sensitivity (<0.4pg/mL), inter-assay repeatability (∼10% CV), and near-real-time operation with a 10min assay incubation. A cytokine profiling test with the platform allowed us to observe clear interleukin −6 (IL-6) elevations after receiving tocilizumab (IL-6 inhibitor) while significant cytokine profile variability exists across all critically ill COVID-19 patients and to discover a weak correlation between IL-6 to clinical biomarkers, such as Ferritin and CRP. Our data revealed large subject-to-subject variability in a patient’s response to anti-inflammatory treatment for COVID-19, reaffirming the need for a personalized strategy guided by rapid cytokine assays.
Prevalence of Chemosensory Dysfunction in COVID-19 Patients: A Systematic Review and Meta-analysis Reveals Significant Ethnic Differences
Authors: von Bartheld Christopher S. , Hagen Molly M. , Butowt Rafal 
Published: June 2020

AbstractA significant fraction of people who test positive for COVID-19 have chemosensory deficits. However, the reported prevalence of these deficits in smell and/or taste varies widely, and the reason for the differences between studies is unclear. We determined the pooled prevalence of such chemosensory deficits in a systematic review. We searched the COVID-19 portfolio of the National Institutes of Health for all studies that reported the prevalence of smell and/or taste deficits in patients diagnosed with COVID-19. Forty-two studies reporting on 23,353 patients qualified and were subjected to a systematic review and meta-analysis. Estimated random prevalence of olfactory dysfunction was 38.5%, of taste dysfunction was 30.4% and of overall chemosensory dysfunction was 50.2%. We examined the effects of age, disease severity, and ethnicity on chemosensory dysfunction. The effect of age did not reach significance, but anosmia/hypogeusia decreased with disease severity, and ethnicity was highly significant: Caucasians had a 3-6 times higher prevalence of chemosensory deficits than East Asians. The finding of ethnic differences points to genetic, ethnicity-specific differences of the virus-binding entry proteins in the olfactory epithelium and taste buds as the most likely explanation, with major implications for infectivity, diagnosis and management of the COVID-19 pandemic.
Seroprevalence of Antibodies to SARS-CoV-2 in Healthcare Workers in Non-epidemic Region: A Hospital Report in Iwate Prefecture, Japan
Authors: Nakamura Akihiro , Sato Ryoichi , Ando Sanae , Oana Natsuko , Nozaki Eiji , Endo Hideaki , Miyate Yoshiharu , Soma Jun , Miyata Go 
Published: June 2020

AbstractBackgroundAs of June 18, 2020, Iwate is the only one of 47 prefectures in Japan with no confirmed coronavirus disease 2019 (COVID-19) cases. Serological survey for COVID-19 antibodies is crucial in area with low prevalence as well as epidemic area when addressing health and social issues caused by COVID-19.MethodsSerum samples from healthcare workers (n = 1,000, mean 40 ± 11 years) of Iwate Prefectural Central Hospital, Iwate, Japan were tested for the prevalence of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) antibodies. Two laboratory-based quantitative tests (Abbott’s and Roche’s immunoassays) and one point-of-care (POC) qualitative test performed simultaneously. Sensitivity and specificity were 100%, 99.6% in Abbott’s immunoassay; 100%, 99.8% in Roche’s immunoassay; 97.8%, 94.6% in Alfa POC test, respectively.ResultsThe laboratory-based quantitative tests showed positive in 4 of 1,000 samples (0.4%) (95% CI: 0.01 to 0.79): 4/1,000 (0.4%) (95% CI: 0.01 to 0.79) in Abbott; 0/1,000 (0%) in Roche. Positive samples were not detected for both Abbott’s and Roche’s immunoassays. The POC qualitative test showed positive in 33 of 1,000 samples (3.3%) (95% CI: 2.19 to 4.41). There were no samples with simultaneous positive reaction for two quantitative tests and a POC test.ConclusionsInfected COVID-2 cases were not confirmed by a retrospective serological study in healthcare workers of our hospital. The POC qualitative tests with lower specificity have the potential for higher false positive reactions than the laboratory-based quantitative tests in areas with very low prevalence of COVID-19.
Mapping the Algal Secret Genome: The small RNA Locus Map forChlamydomonas reinhardtii
Authors: Müller Sebastian Y. , Matthews Nicholas E. , Valli Adrian A. , Baulcombe David C. 
Published: June 2020

AbstractSmall (s)RNAs play crucial roles in the regulation of gene expression and genome stability across eukaryotes where they direct epigenetic modifications, post-transcriptional gene silencing, and defense against both endogenous and exogenous viruses. The green algaChlamydomonas reinhardtiiis a well-studied unicellular alga species with sRNA-based mechanisms that are distinct from those of land plants. It is, therefore, a good model to study sRNA evolution but a systematic classification of sRNA mechanisms is lacking in this and any other algae. Here, using data-driven machine learning approaches including Multiple Correspondence Analysis (MCA) and clustering, we have generated a comprehensively annotated and classified sRNA locus map for C. reinhardtii. This map shows some common characteristics with higher plants and animals, but it also reveals distinct features. These results are consistent with the idea that there was diversification in sRNA mechanisms after the evolutionary divergence of algae from higher plant lineages.
Joint nonparametric coalescent inference of mutation spectrum history and demography
Authors: DeWitt William S. , Harris Kameron Decker , Harris Kelley 
Published: June 2020

AbstractBooming and busting populations modulate the accumulation of genetic diversity, encoding histories of living populations in present-day variation. Many methods exist to decode these histories, and all must make strong model assumptions. It is typical to assume that mutations accumulate uniformly across the genome at a constant rate that does not vary between closely related populations. However, recent work shows that mutational processes in human and great ape populations vary across genomic regions and evolve over time. This perturbs themutation spectrum: the relative mutation rates in different local nucleotide contexts. Here, we develop theoretical tools in the framework of Kingman’s coalescent to accommodate mutation spectrum dynamics. We describemushi: a method to perform fast, nonparametric joint inference of demographic and mutation spectrum histories from allele frequency data. We usemushito reconstruct trajectories of effective population size and mutation spectrum divergence between human populations, identify mutation signatures and their dynamics in different human populations, and produce more accurate time calibration for a previously-reported mutational pulse in the ancestors of Europeans. We show that mutation spectrum histories can be productively incorporated in a well-studied theoretical setting, and rigorously inferred from genomic variation data like other features of evolutionary history.
Population genomic time series data of a natural population suggests adaptive tracking of environmental changes
Authors: Pfenninger Markus , Foucault Quentin 
Published: June 2020

AbstractNatural populations are constantly exposed to fluctuating environmental changes that negatively affect their fitness in unpredictable ways. While theoretical models show the possibility of counteracting these environmental changes through rapid evolutionary adaptations, there have been few empirical studies demonstrating such adaptive tracking in natural populations.Here, we analysed environmental data, fitness-related phenotyping and genomic time-series data sampled over three years from a natural Chironomus riparius (Diptera, Insecta) population to address this question. We show that the population’s environment varied significantly on the time scale of the sampling in many selectively relevant dimensions, independently of each other. Similarly, phenotypic fitness components evolved significantly on the same temporal scale (mean 0.32 Haldanes), likewise independent from each other. The allele frequencies of 367,446 SNPs across the genome showed evidence of positive selection. Using temporal correlation of spatially coherent allele frequency changes revealed 35,574 haplotypes with more than one selected SNP. The mean selection coefficient for these haplotypes was 0.30 (s.d. = 0.68). The frequency changes of these haplotypes clustered in 46 different temporal patterns, indicating concerted, independent evolution of many polygenic traits. Nine of these patterns were strongly correlated with measured environmental variables.Thus, our results suggest that the natural population of C. riparius tracks environmental change through rapid polygenic adaptation in many independent dimensions. This is further evidence that natural selection is pervasive at the genomic level and that evolutionary and ecological time scales may not differ at all, at least in some organisms.
Experimental methodologies can affect pathogenicity ofBatrachochytrium salamandrivoransinfections
Authors: Kumar Rajeev , Malagon Daniel A. , Carter Edward Davis , Miller Debra L. , Bohanon Markese L. , Cusaac Joseph Patrick W. , Peterson Anna C. , Gray Matthew J. 
Published: June 2020

AbstractControlled experiments are one approach to understanding the pathogenicity of etiologic agents to susceptible hosts. The recently discovered fungal pathogen,Batrachochytrium salamandrivorans(Bsal), has resulted in a surge of experimental investigations because of its potential to impact global salamander biodiversity. However, variation in experimental methodologies could thwart knowledge advancement by introducing confounding factors that make comparisons difficult among studies. Thus, our objective was to evaluate if variation in experimental methods changed inferences made on the pathogenicity ofBsal. We tested whether passage duration ofBsalculture, exposure method of the host toBsal(water bath vs. skin inoculation),Bsalculturing method (liquid vs. plated), host husbandry conditions (aquatic vs. terrestrial), and skin swabbing frequency influenced diseased-induced mortality in a susceptible host species, the eastern newt (Notophthalmus viridescens). We found that disease-induced mortality was faster for eastern newts when exposed to a low passage isolate, when newts were housed in terrestrial environments, and if exposure to zoospores occurred via water bath. We did not detect differences in disease-induced mortality between culturing methods or swabbing frequencies. Our results illustrate the need to standardize methods amongBsalexperiments; we provide suggestions for future experiments in the context of hypothesis testing.
Development of a sensitive molecular diagnostic assay for detectingBorrelia burgdorferiDNA from blood of Lyme disease patients by digital PCR
Authors: Das Srirupa , Hammond-McKibben Denise , Guralski Donna , Lobo Sandra , Fiedler Paul N. 
Published: June 2020

AbstractLyme disease patients would benefit greatly from a timely, sensitive and specific molecular diagnostic test that can detect the causal agent,Borrelia burgdorferi, at the onset of symptoms. Currently available diagnostic methods recommended by the Centers for Disease Control and Prevention for Lyme disease, involve indirect serological tests that rely on the detection of a host-antibody response which often takes more than three weeks to develop. This results in non-detection of many genuine cases on a timely basis, preventing complete cure. In this study we have developed a digital PCR (polymerase chain reaction) assay that detects Lyme disease on clinical presentation at twice the sensitivity of the currently available diagnostic methods, using a cohort of patient samples collected from the Lyme disease endemic state of Connecticut, USA in 2016-2018. Digital PCR technology was chosen as it is more advanced and sensitive than other PCR techniques in detecting rare targets and the lower limit of detection of this diagnostic assay was found to be three genome copies ofB. burgdorferi. The paucity of spirochetes in the bloodstream of Lyme disease patients that hinders the clinical adoption of PCR-based diagnostic tests, was overcome by using a comparatively larger sample volume, pre-analytical processing of blood samples and a pre-amplification step to enrich forB. burgdorferi-specific gene targets before using the digital PCR technology to analyze patient samples. Pre-analytical processing of blood samples from acute patients revealed that the best sample type for Lyme disease detection is platelet-rich plasma and not whole blood. If detected on time, Lyme disease can be cured completely limiting the overuse of antibiotics and associated morbidities.
Conditional Protein Rescue (CPR) by Binding-Induced Protective Shielding
Authors: Gaynor Andrew S. , Chen Wilfred 
Published: June 2020

AbstractAn effective method to modulate the stability of proteins is essential to biological research. Herein, we describe a new technology that allows conditional stabilization of proteins based on masking of a degron tag by a specific intracellular protein cue. A target protein is fused to a degron tag and an affinity sensor domain. When the sensor detects its target protein, the degron is effectively concealed and the target protein is rescued. By introducing nanobodies as the sensor, we allow for virtually any endogenous protein to be targeted. In a model system using yeast cytosine deaminase, we demonstrate low cell death background yet maintain the ability to elicit strong activation and prodrug-mediated cell killing using GFP as the rescue protein. The flexibility in choosing different masking targets provides a straightforward method to generalize the strategy for conditional protein rescue in a wide range of biological contexts, including oncoprotein detection.
Cortico-hippocampal morphology and behavioural indices improved in maternal deprivation model of schizophrenia following vitamin B complex supplementation
Authors: Omotoso Gabriel Olaiya , Abdulsalam Fatimah Adeola , Mutholib Nafisat Yetunde , Bature Abdulkabir , Gbadamosi Ismail Temitayo 
Published: June 2020

ABSTRACTMaternal deprivation (MD) during early life development has been documented to culminate in long-term alterations in brain function and behavioural manifestations that mimic schizophrenia. This study elucidated the putative neuroprotective roles of vitamin B complex in MD-induced behavioural and neurochemical modifications in hippocampus and prefrontal cortex of Wistar rats. Rat pups were maternally deprived on postnatal day 9 for 24 hours and then treated with or without vitamin B complex for 15 days while a control group was undisturbed during the experimental period. The rats were then subjected to behavioural paradigms to measure memory indices and anxiety levels. The rats were sacrificed to obtain the PFC and hippocampus for histomorphological and biochemical analysis. Behavioural analysis of the animals revealed that MD induced a declination in long- and short-term memory in addition to anxiety-like behaviour in the open field test. Cortico-hippocampal histomorphology of these animals showed an increased astrocytic density and chromatolysis, which were accompanied by reduced levels of superoxide dismutase and catalase enzymes. Vitamin B complex mitigated MD-induced behavioural decline, histomorphological perturbation and oxidative stress by enhancing the intrinsic antioxidant defence, thereby culminating in nootropic behaviour and reduced anxiety. In conclusion, we confirmed the hypothesis that vitamin B complex is neuroprotective against neuropathological alterations induced by maternal deprivation.
Simulating a Primary Visual Cortex at the Front of CNNs Improves Robustness to Image Perturbations
Authors: Dapello Joel , Marques Tiago , Schrimpf Martin , Geiger Franziska , Cox David D. , DiCarlo James J. 
Published: June 2020

AbstractCurrent state-of-the-art object recognition models are largely based on convolutional neural network (CNN) architectures, which are loosely inspired by the primate visual system. However, these CNNs can be fooled by imperceptibly small, explicitly crafted perturbations, and struggle to recognize objects in corrupted images that are easily recognized by humans. Here, by making comparisons with primate neural data, we first observed that CNN models with a neural hidden layer that better matches primate primary visual cortex (V1) are also more robust to adversarial attacks. Inspired by this observation, we developed VOneNets, a new class of hybrid CNN vision models. Each VOneNet contains a fixed weight neural network front-end that simulates primate V1, called the VOneBlock, followed by a neural network back-end adapted from current CNN vision models. The VOneBlock is based on a classical neuroscientific model of V1: the linear-nonlinear-Poisson model, consisting of a biologically-constrained Gabor filter bank, simple and complex cell nonlinearities, and a V1 neuronal stochasticity generator. After training, VOneNets retain high ImageNet performance, but each is substantially more robust, outperforming the base CNNs and state-of-the-art methods by 18% and 3%, respectively, on a conglomerate benchmark of perturbations comprised of white box adversarial attacks and common image corruptions. Finally, we show that all components of the VOneBlock work in synergy to improve robustness. While current CNN architectures are arguably brain-inspired, the results presented here demonstrate that more precisely mimicking just one stage of the primate visual system leads to new gains in ImageNet-level computer vision applications.
Ermin deficiency as an inside-out model of inflammatory dysmyelination
Authors: Ziaei Amin , Garcia-Miralles Marta , Radulescu Carola I. , Sidik Harwin , Silvin Aymeric , Bae Han-Gyu , Bonnard Carine , Mohammad Yusof Nur Amirah Binte , Bardile Costanza Ferrari , Tan Liang Juin , Ng Alvin Yu Jin , Tohari Sumanty , Dehghani Leila , Venkatesh Byrappa , Langley Sarah R. , Shaygannejad Vahid , Reversade Bruno , Jung Sangyong , Ginhoux Florent , Pouladi Mahmoud A. 
Published: June 2020

ABSTRACTErmin is an actin-binding protein found almost exclusively in the central nervous system (CNS) as a component of myelin sheaths. Although Ermin has been predicted to play a role in the formation and stability of myelin sheaths, this has not been directly examinedin vivo. Here we show that Ermin is essential for myelin sheath integrity and normal saltatory conduction. Loss of Ermin in mice caused de-compacted and fragmented myelin sheaths and led to slower conduction along with progressive neurological deficits. RNA sequencing of the corpus callosum, the largest white matter structure in the CNS, pointed to inflammatory activation in aged Ermin-deficient mice, which was corroborated by increased levels of microgliosis and astrogliosis. The inflammatory milieu and myelin abnormalities were further associated with increased susceptibility to immune-mediated demyelination insult in Ermin knockout mice. Supporting a possible role of Ermin deficiency in inflammatory white matter disorders, a rare inactivating mutation in theERMNgene was identified in multiple sclerosis patients. Our findings demonstrate a critical role for Ermin in maintaining myelin integrity. Given its near exclusive expression in myelinating oligodendrocytes, Ermin deficiency represents a compelling “inside-out” model of inflammatory dysmyelination and may offer a new paradigm for the development of myelin stability-targeted therapies.
Maternal cortisol is associated with neonatal amygdala microstructure and connectivity in a sexually dimorphic manner
Authors: Stoye David Q , Blesa Manuel , Sullivan Gemma , Galdi Paola , Lamb Gillian J , Black Gill S , Quigley Alan J , Thrippleton Michael J , Bastin Mark E , Reynolds Rebecca M , Boardman James P 
Published: June 2020

AbstractThe mechanisms linking maternal stress in pregnancy with infant neurodevelopment in a sexually dimorphic manner are poorly understood. We tested the hypothesis that maternal hypothalamic-pituitary-adrenal axis activity, measured by hair cortisol concentration, is associated with microstructure, structural connectivity and volume of the infant amygdala. In 78 human mother-infant dyads, maternal hair was sampled postnatally, and infants underwent magnetic resonance imaging at term-equivalent age. Higher hair cortisol concentration was associated with higher left amygdala fractional anisotropy (β=0.677, p=0.010), lower left amygdala orientation dispersion index (β=-0.597, p=0.034), and higher fractional anisotropy in connections between the right amygdala and putamen (β=0.475, p=0.007) in girls compared to boys. Maternal cortisol during pregnancy is related to newborn amygdala architecture and connectivity in a sexually dimorphic manner. Given the fundamental role of the amygdala in the emergence of emotion regulation, these findings offer new insights into mechanisms linking maternal stress with adverse neuropsychiatric outcomes of children.Impact StatementPrenatal stress is transmitted to infant development through cortisol, which imparts sex-specific effects on the development and connectivity of the amygdalae.
A reference-guided approach for epigenetic characterization of single cells
Authors: Chen Shengquan , Yan Guanao , Zhang Wenyu , Li Jinzhao , Jiang Rui , Lin Zhixiang 
Published: June 2020

AbstractThe recent advancements in single-cell technologies, including single-cell chromatin accessibility sequencing (scCAS), have enabled profiling the epigenetic landscapes for thousands of individual cells. However, the characteristics of scCAS data, including high dimensionality, high degree of sparsity and high technical variation, make the computational analysis challenging. Reference-guided approach, which utilizes the information in existing datasets, may facilitate the analysis of scCAS data. We present RA3 (Reference-guided Approach for the Analysis of single-cell chromatin Acessibility data), which utilizes the information in massive existing bulk chromatin accessibility and annotated scCAS data. RA3 simultaneously models 1) the shared biological variation among scCAS data and the reference data, and 2) the unique biological variation in scCAS data that identifies distinct subpopulations. We show that RA3 achieves superior performance in many scCAS datasets. We also present several approaches to construct the reference data to demonstrate the wide applicability of RA3.