bluuebunny/crossref_metadata_2025_split huggingface dataset:
Learning Phenotypic Associations for Parkinson’s Disease with Longitudinal Clinical Records
Authors: Pan Weishen , Su Chang , Chen Kun , Henchcliffe Claire , Wang Fei 
Published: March 2020

AbstractBackgroundParkinson’s disease (PD) is associated with multiple clinical manifestations including motor and non-motor symptoms, and understanding of its etiologies has been informed by a growing number of genetic mutations, and various fluid-based and brain imaging biomarkers. However, the precise mechanisms by which these phenotypic features interact remain elusive. Therefore, we aimed to generate the phenotypic association graph of multiple heterogeneous features within PD to reveal pathological pathways of the complex disease.MethodsA data-driven approach was introduced to generate the phenotypic association graphs using data from the Parkinson’s Progression Markers Initiative (PPMI) and Fox Investigation for New Discovery of Biomarkers (BioFIND) studies. We grouped features based on the structure of the learned graphs in both cohorts, and investigated their dynamic patterns in the longitudinal PPMI cohort.Findings424 patients with PD from the PPMI study and 126 patients with PD from the BioFIND study were available for analysis. For PPMI, the phenotypic association graphs were generated at different time points of the disease, including baseline (without any PD treatments), and 1-, 2-, 3-, 4-, and 5-year follow-up time points. Based on topological structure of the learned graph, clinical features were classified into homogeneous groups, that were densely intra-connected while sparsely inter-connected. Importantly, we observed both stable and longitudinally changing relations in the graphs generated, likely reflecting the dynamic pathologies of PD. By cross-cohort comparison, we observed very similar structure for graphs constructed from BioFIND (in which patients have a much longer duration of PD at enrollment than PPMI) and later-period (4- and 5-year follow-up) data from PPMI. This consistency demonstrates the effectiveness of our method.InterpretationWe analyzed the heterogeneous features of PD by generating the phenotypic association graphs. By analyzing the structural relationships among the features over time, our findings could improve the understanding of the pathologies of PD.FundingMichael J Fox Foundation for Parkinson’s Research.
Temporal dynamics in viral shedding and transmissibility of COVID-19
Authors: He Xi , Lau Eric HY , Wu Peng , Deng Xilong , Wang Jian , Hao Xinxin , Lau Yiu Chung , Wong Jessica Y , Guan Yujuan , Tan Xinghua , Mo Xiaoneng , Chen Yanqing , Liao Baolin , Chen Weilie , Hu Fengyu , Zhang Qing , Zhong Mingqiu , Wu Yanrong , Zhao Lingzhai , Zhang Fuchun , Cowling Benjamin J , Li Fang , Leung Gabriel M 
Published: March 2020

ABSTRACTWe report temporal patterns of viral shedding in 94 laboratory-confirmed COVID-19 patients and modelled COVID-19 infectiousness profile from a separate sample of 77 infector-infectee transmission pairs. We observed the highest viral load in throat swabs at the time of symptom onset, and inferred that infectiousness peaked on or before symptom onset. We estimated that 44% of transmission could occur before first symptoms of the index. Disease control measures should be adjusted to account for probable substantial pre-symptomatic transmission.
Motivational Strategies for Stroke Rehabilitation: A Delphi Study
Authors: Oyake Kazuaki , Suzuki Makoto , Otaka Yokei , Momose Kimito , Tanaka Satoshi 
Published: March 2020

AbstractBackground and PurposeAlthough various strategies are used to motivate patients during rehabilitation, consensus regarding the optimal motivational strategies for stroke rehabilitation has not been established. Expert consensus may aid rehabilitation professionals in effectively utilizing motivational strategies to produce the most beneficial outcome for their patients. The primary purpose of this study was to provide a comprehensive list of effective motivational strategies based on consensus among rehabilitation experts, generated using the Delphi technique. In addition, we sought to identify the types of information that are important when selecting motivational strategies.MethodsA total of 198 rehabilitation experts participated in a three-round Delphi survey. The rehabilitation experts included physicians, physical therapists, occupational therapists, and speech-language-hearing therapists who had worked in stroke rehabilitation for at least five years. Panelists were asked to rate the effectiveness of motivational strategies and to rate the importance of different types of information using a 5-point Likert scale. Consensus was defined as having been reached for items with an interquartile range of 1 or less.ResultsA total of 116 experts (58.6%) completed the third round of the Delphi survey. Consensus was reached on all of the 26 presented strategies. Seven strategies, such as control of task difficulty and goal setting, were considered to be very effective in increasing patient motivation. In addition, all 11 of the presented types of information were deemed very important or important in determining which motivational strategies to use.ConclusionsWe generated a list of effective motivational strategies for stroke rehabilitation based on expert consensus. Our results suggest that experts consider a comprehensive range of patient information when choosing motivational strategies. These findings represent a group of consensus-based recommendations for increasing patient adherence to stroke rehabilitation programs, which may be beneficial to many medical professionals working in stroke rehabilitation.
Recovery Units under the Endangered Species Act could be used more widely
Authors: Evans Michael , Li Ya-Wei , Malcom Jacob 
Published: March 2020

AbstractRecovering species is one of the main goals of the Endangered Species Act (ESA). In the face of limited budgets, diverse tools are needed to find efficient solutions. Recovery units may be one such tool - designated portions of a species’ range that must be recovered individually before an entire species can be considered recovered. Recovery units allow for spatial flexibility in recovery goals and may be used in regulatory decisions such as section 7 consultation. Despite their availability, there is very little information on how recovery units have been developed and used. We mined available public data to determine the number and types of species for which recovery units have been designated; evaluated species and geographic characteristics associated with recovery unit designation; and examined how recovery units have been used in the implementation of the ESA, such as during consultation. We found 49 listed species have designated recovery units through 2017, and that these species had similar characteristics. Namely, they had relatively large ranges and were well-studied. We found taxonomic biases in recovery unit designation as well, with fish species being disproportionately likely to have recovery units and plants disproportionately less. Improvements in recovery priority numbers among species with recovery units indicate that the theoretical benefits of this tool may have translated to improved status. These data indicate that recovery units could be applied to more wide-ranging species to improve recovery under the ESA.
The positive evidence bias in perceptual confidence is not post-decisional
Authors: Samaha Jason , Denison Rachel 
Published: March 2020

AbstractConfidence in a perceptual decision is a subjective estimate of the accuracy of one’s choice. As such, confidence is thought to be an important computation for a variety of cognitive and perceptual processes, and it features heavily in theorizing about conscious access to perceptual states. Recent experiments have revealed a “positive evidence bias” (PEB) in the computations underlying confidence reports. A PEB occurs when confidence, unlike objective choice, over-weights the evidence for the chosen option, relative to evidence against the chosen option. Accordingly, in a perceptual task, appropriate stimulus conditions can be arranged that produce selective changes in confidence reports but no changes in accuracy. Although the PEB is generally assumed to reflect the observer’s perceptual and/or decision processes, post-decisional accounts have not been ruled out. We therefore asked whether the PEB persisted under novel conditions that eliminated two possible post-decisional accounts: 1) post-decision evidence accumulation that contributes to a confidence report solicited after the perceptual choice, and 2) a memory bias that emerges in the delay between the stimulus offset and the confidence report. We found that even when the stimulus remained on the screen until observers responded, and when observers reported their choice and confidence simultaneously, the PEB still emerged. Signal detection-based modeling also showed that the PEB was not associated with changes to metacognitive efficiency, but rather to confidence criteria. We conclude that once-plausible post-decisional accounts of the PEB do not explain the bias, bolstering the idea that it is perceptual or decisional in nature.
Functional Organization of the Maternal and Paternal Human 4D Nucleome
Authors: Lindsly Stephen , Jia Wenlong , Chen Haiming , Liu Sijia , Ronquist Scott , Chen Can , Wen Xingzhao , Stansbury Cooper , Dotson Gabrielle A. , Ryan Charles , Rehemtulla Alnawaz , Omenn Gilbert S. , Wicha Max , Li Shuai Cheng , Muir Lindsey , Rajapakse Indika 
Published: March 2020

AbstractEvery human somatic cell inherits a maternal and a paternal genome, which work together to give rise to cellular phenotypes. However, the allele-specific relationship between gene expression and genome structure through the cell cycle is largely unknown. By integrating haplotype-resolved genome-wide chromosome conformation capture, mature and nascent mRNA, and protein binding data, we investigate this relationship both globally and locally. We introduce the maternal and paternal 4D Nucleome, enabling detailed analysis of the mechanisms and dynamics of genome structure and gene function for diploid organisms. Our analyses find significant coordination between allelic expression biases and local genome conformation, and notably absent expression bias in universally essential cell cycle and glycolysis genes. We propose a model in which coordinated biallelic expression reflects prioritized preservation of essential gene sets.
Adversarial manipulation of human decision-making
Authors: Dezfouli Amir , Nock Richard , Dayan Peter 
Published: March 2020

AbstractAdversarial examples are carefully crafted input patterns that are surprisingly poorly classified by artificial and/or natural neural networks. Here we examine adversarial vulnerabilities in the processes responsible for learning and choice in humans. Building upon recent recurrent neural network models of choice processes, we propose a general framework for generating adversarial opponents that can shape the choices of individuals in particular decision-making tasks towards the behavioural patterns desired by the adversary. We show the efficacy of the framework through two experiments involving action selection and response inhibition. We further investigate the strategy used by the adversary in order to gain insights into the vulnerabilities of human choice. The framework may find applications across behavioural sciences in helping detect and avoid flawed choice.
Whole exome sequencing identifies novel DYT1 dystonia-associated genome variants as potential disease modifiers
Authors: Hu Chih-Fen , Luxton G. W. Gant , Lee Feng-Chin , Hsu Chih-Sin , Huang Shih-Ming , Hong Jau-Shyong , Wu San-Pin 
Published: March 2020

AbstractBackgroundDYT1 dystonia is a neurological movement disorder characterized by painful sustained muscle contractions resulting in abnormal twisting and postures. In a subset of patients, it is caused by a loss-of-function mutation (ΔE302/303; or ΔE) in the luminal ATPases associated with various cellular activities (AAA+) protein torsinA encoded by theTOR1Agene. The low penetrance of the ΔE mutation (∼30-40%) suggests the existence of unknown genetic modifiers of DYT1 dystonia.MethodsTo identify these modifiers, we performed whole exome sequencing of blood leukocyte DNA isolated from two DYT1 dystonia patients, three asymptomatic carriers of the ΔE mutation, and an unaffected adult relative.ResultsA total of 264 DYT1 dystonia-associated variants (DYT1 variants) were identified in 195 genes. Consistent with the emerging view of torsinA as an important regulator of the cytoskeleton, endoplasmic reticulum homeostasis, and lipid metabolism, we found DYT1 variants in genes that encode proteins implicated in these processes. Moreover, 40 DYT1 variants were detected in 32 genes associated with neuromuscular and neuropsychiatric disorders.ConclusionThe DYT1 variants described in this work represent exciting new targets for future studies designed to increase our understanding of the pathophysiology and pathogenesis of DYT1 dystonia.
Mating type specific transcriptomic response to sex inducing pheromone in the pennate diatomSeminavis robusta
Authors: Bilcke Gust , Van den Berge Koen , De Decker Sam , Bonneure Eli , Poulsen Nicole , Bulankova Petra , Osuna-Cruz Cristina Maria , Dickenson Jack , Sabbe Koen , Pohnert Georg , Vandepoele Klaas , Mangelinckx Sven , Clement Lieven , De Veylder Lieven , Vyverman Wim 
Published: March 2020

AbstractSexual reproduction is a fundamental phase in the life cycle of most diatoms. Despite its role as a source of genetic variation, it is rarely reported in nature and its molecular foundations remain largely unknown. Here, we integrate independent transcriptomic datasets, in order to prioritize genes responding to sex inducing pheromones (SIPs) in the pennate diatomSeminavis robusta. We observe marked gene expression changes associated with SIP treatment in both mating types, including an inhibition of S-phase progression, chloroplast division, mitosis and cell wall formation. Meanwhile, meiotic genes are upregulated in response to SIP, including a sexually induced diatom specific cyclin (dsCyc). Our data further suggest an important role for reactive oxygen species, energy metabolism and cGMP signaling during the early stages of sexual reproduction. In addition, we identify several genes with a mating type specific response to SIP, and link their expression pattern with physiological responses such as the production of the attraction pheromone diproline and mate-searching behaviour in MT+. Combined, our results provide a model for early sexual reproduction in pennate diatoms and significantly expand the suite of target genes to detect sexual reproduction events in natural diatom populations.
miRNome profiling of clonal stem cells in Ph+CML
Authors: Ruiz María Sol , Sánchez María Belén , Bonecker Simone , Furtado Carolina , Koile Daniel , Yankilevich Patricio , Cranco Santiago , del Rosario Custidiano María , Freitas Josefina , Moiraghi Beatriz , Peréz Mariel Ana , Pavlovsky Carolina , Varela Ana Inés , Ventriglia Verónica , Sánchez Ávalos Julio César , Larripa Irene , Zalcberg Ilana , Mordoh José , Valent Peter , Bianchini Michele 
Published: March 2020

AbstractChronic myeloid leukemia (CML) is a myeloid stem cell neoplasm characterized by an expansion of myeloid progenitor cells and the presence of BCR-ABL1 oncoprotein. Since the introduction of specific BCR-ABL1 tyrosine kinase inhibitors (TKI), overall survival has improved significantly. However, under long-term therapy patients may have residual disease that originates from TKI-resistant leukemic stem cells (LSC). In this work, we analyzed the miRNome of CML LSC, normal hematopoietic stem cells (HSC) obtained from the same CML patients, and stem and progenitor cells obtained from healthy donors (HD) by next-generation sequencing. We detected a global decrease of microRNA levels in LSC and HSC from CML patients, and decreased levels of microRNAs and snoRNAs from a genomic cluster in chromosome 14, suggesting a mechanism of silencing of multiple non-coding RNAs. Surprisingly, HSC from CML patients, despite the absence ofBCR-ABL1expression, showed an altered miRNome.In silicoanalysis revealed an association between validated microRNAs and multiple metabolic pathways, suggesting that these molecules may be mediators of the previously reported dysregulation of LSC metabolism. This is the first report of the LSC miRNome that distinguishes betweenBCR-ABL1+LSC and theirBCR-ABL1-counterparts, providing valuable data for future studies.
Structure of human ferroportin bound to hepcidin reveals mechanisms of iron homeostasis
Authors: Billesbølle Christian B. , Azumaya Caleigh M. , Kretsch Rachael C. , Powers Alexander S. , Gonen Shane , Schneider Simon , Arvedson Tara , Dror Ron O. , Cheng Yifan , Manglik Aashish 
Published: March 2020

AbstractThe serum iron level in humans is tightly controlled by the action of the hormone hepcidin on the iron efflux transporter ferroportin. Hepcidin negatively regulates iron absorption and recycling by inducing ferroportin internalization and degradation. Aberrant ferroportin activity can lead to diseases of iron overload, like hemochromatosis, or iron limitation anemias. Here, we determined cryogenic electron microscopy (cryo-EM) structures of ferroportin in lipid nanodiscs, both in the apo state and in complex with cobalt, an iron mimetic, and hepcidin. These structures and accompanying molecular dynamics simulations identify two divalent metal binding sites within the N- and C-domains of ferroportin. Hepcidin binds ferroportin in an outward-open conformation and completely occludes the iron efflux pathway. The carboxy-terminus of hepcidin directly contacts the divalent metal in the FPN C-domain. We further show that hepcidin binding to ferroportin is coupled to iron binding, with an 80-fold increase in hepcidin affinity in the presence of iron. These results suggest a new model for hepcidin regulation of ferroportin, where only iron loaded ferroportin molecules are targeted for degradation. More broadly, our structural and functional insights are likely to enable more targeted manipulation of the hepcidin-ferroportin axis in disorders of iron homeostasis.
The polyol pathway is a crucial glucose sensor inDrosophila
Authors: Sano Hiroko , Nakamura Akira , Yamane Mariko , Niwa Hitoshi , Nishimura Takashi , Kojima Masayasu 
Published: March 2020

SummaryA major nutrient source for animals is glucose, which induces transcriptional responses that shift metabolism. Such metabolic adaptation should be appropriately scaled to the ingested glucose levels, and decoupling causes human metabolic diseases. However, the identity of the crucial sensor metabolite(s) that transmit circulating glucose levels to the transcriptional machinery remains elusive. Here we show that the polyol pathway, which converts glucose to fructose via sorbitol, is required for activation of the master metabolic regulator Mondo, theDrosophilahomologue of MondoA/ChREBP. We demonstrate that under normal nutritional conditions polyol pathway metabolites promote Mondo’s nuclear localization and cause global changes in metabolic gene expression. Polyol pathway mutants block nuclear localization of Mondo and Mondo-mediated gene expression despite intact glycolytic and pentose phosphate pathways. Our results uncover the normal physiological function of this pathway and cast a new light on the adverse effects of high fructose diets in human health.
Structure of RNA-dependent RNA polymerase from 2019-nCoV, a major antiviral drug target
Authors: Gao Yan , Yan Liming , Huang Yucen , Liu Fengjiang , Zhao Yao , Cao Lin , Wang Tao , Sun Qianqian , Ming Zhenhua , Zhang Lianqi , Ge Ji , Zheng Litao , Zhang Ying , Wang Haofeng , Zhu Yan , Zhu Chen , Hu Tianyu , Hua Tian , Zhang Bing , Yang Xiuna , Li Jun , Yang Haitao , Liu Zhijie , Xu Wenqing , Guddat Luke W. , Wang Quan , Lou Zhiyong , Rao Zihe 
Published: March 2020

AbstractA novel coronavirus (2019-nCoV) outbreak has caused a global pandemic resulting in tens of thousands of infections and thousands of deaths worldwide. The RNA-dependent RNA polymerase (RdRp, also named nsp12), which catalyzes the synthesis of viral RNA, is a key component of coronaviral replication/transcription machinery and appears to be a primary target for the antiviral drug, remdesivir. Here we report the cryo-EM structure of 2019-nCoV full-length nsp12 in complex with cofactors nsp7 and nsp8 at a resolution of 2.9-Å. Additional to the conserved architecture of the polymerase core of the viral polymerase family and a nidovirus RdRp-associated nucleotidyltransferase (NiRAN) domain featured in coronaviral RdRp, nsp12 possesses a newly identified β-hairpin domain at its N-terminal. Key residues for viral replication and transcription are observed. A comparative analysis to show how remdesivir binds to this polymerase is also provided. This structure provides insight into the central component of coronaviral replication/transcription machinery and sheds light on the design of new antiviral therapeutics targeting viral RdRp.One Sentence SummaryStructure of 2019-nCov RNA polymerase.
The ribosomal RNA m5C methyltransferase NSUN-1 modulates healthspan and oogenesis inCaenorhabditis elegans
Authors: Heissenberger Clemens , Krammer Teresa L. , Rollins Jarod A. , Nagelreiter Fabian , Stocker Isabella , Wacheul Ludivine , Shpylovyi Anton , Snow Santina , Grillari Johannes , Rogers Aric N. , Lafontaine Denis L.J. , Schosserer Markus 
Published: March 2020

AbstractOur knowledge about the repertoire of ribosomal RNA modifications and the enzymes responsible for installing them is constantly expanding. Previously, we reported that NSUN-5 is responsible for depositing m5C at position C2381 on the 26S rRNA inCaenorhabditis elegans.Here, we show that NSUN-1 is writing the second known 26S rRNA m5C at position C2982. Depletion ofnsun-1ornsun-5improved locomotion at midlife and resistance against heat stress, however, only soma-specific knockdown ofnsun-1extended lifespan. Moreover, soma-specific knockdown ofnsun-1reduced body size and impaired fecundity, suggesting non-cell-autonomous effects. While ribosome biogenesis and global protein synthesis were unaffected bynsun-1depletion, translation of specific mRNAs was remodelled leading to reduced production of collagens, loss of structural integrity of the cuticle and impaired barrier function.We conclude that loss of a single enzyme required for rRNA methylation has profound and highly specific effects on organismal physiology.
Multiple approaches for massively parallel sequencing of HCoV-19 (SARS-CoV-2) genomes directly from clinical samples
Authors: Xiao Minfeng , Liu Xiaoqing , Ji Jingkai , Li Min , Li Jiandong , Yang Lin , Sun Wanying , Ren Peidi , Yang Guifang , Zhao Jincun , Liang Tianzhu , Ren Huahui , Chen Tian , Zhong Huanzi , Song Wenchen , Wang Yanqun , Deng Ziqing , Zhao Yanping , Ou Zhihua , Wang Daxi , Cai Jielun , Cheng Xinyi , Feng Taiqing , Wu Honglong , Gong Yanping , Yang Huanming , Wang Jian , Xu Xun , Zhu Shida , Chen Fang , Zhang Yanyan , Chen Weijun , Li Yimin , Li Junhua 
Published: March 2020

ABSTRACTCOVID-19 has caused a major epidemic worldwide, however, much is yet to be known about the epidemiology and evolution of the virus. One reason is that the challenges underneath sequencing HCoV-19 directly from clinical samples have not been completely tackled. Here we illustrate the application of amplicon and hybrid capture (capture)-based sequencing, as well as ultra-high-throughput metatranscriptomic (meta) sequencing in retrieving complete genomes, inter-individual and intra-individual variations of HCoV-19 from clinical samples covering a range of sample types and viral load. We also examine and compare the bias, sensitivity, accuracy, and other characteristics of these approaches in a comprehensive manner. This is, to date, the first work systematically implements amplicon and capture approaches in sequencing HCoV-19, as well as the first comparative study across methods. Our work offers practical solutions for genome sequencing and analyses of HCoV-19 and other emerging viruses.