bluuebunny/crossref_metadata_2025_split huggingface dataset:
Addressing Extreme Imbalance for Detecting Medications Mentioned in Twitter User Timelines
Authors: Weissenbacher Davy , Rawal Siddharth , Magge Arjun , Gonzalez-Hernandez Graciela 
Published: February 2021

AbstractTweets mentioning medications are valuable for efforts in digital epidemiology to supplement traditional methods of monitoring public health. A major obstacle, however, is to differentiate them from the large majority of tweets on other topics posted in a user’s timeline: solving the infamous ‘needle in a haystack’ problem. While deep learning models have significantly improved classification, their performance and inference processing time remain low on extremely imbalanced corpora where the tweets of interest are less than 1% of all tweets. In this study, we empirically evaluate under-sampling, fine-tuning, and filtering heuristics to train such classifiers. Using a corpus of 212 Twitter timelines (181,607 tweets with only 0.2% tweets mentioning a medication), our results show that combining these heuristics is necessary to impact the classifier’s performance. In our intrinsic evaluation, a classifier based on a lexicon and a BERT-base neural network achieved a 0.838 F1-score, a score similar to the ones of the best existing classifier, but it processed the corpus 28 times faster - a positive result, since processing speed is still a roadblock to deploying classifiers on large cohorts of Twitter users needed for pharmacovigilance. In our extrinsic evaluation, our classifier helped a labeler to extract the spans of medications more accurately and achieved a 0.76 Strict F1-score. To the best of our knowledge, this is the first evaluation of medications extraction in Twitter timelines and it establishes the first benchmark for future studies.
Timely referral for advanced therapy in Parkinson’s disease. Development of a screening tool
Authors: Moes Harmen R. , ten Kate Jolien , Portman Axel T. , van Harten Barbera , van Kesteren Mirjam E. , Mondria Tjeerd , Lunter Gerton , Buskens Erik , van Laar Teus 
Published: February 2021

AbstractObjectivesTo develop a screening tool for timely referral for advanced therapy (AT) in patients with Parkinson’s disease (PD), and to compare the newly-developed tool with the published 5-2-1 criteria.DesignCross-sectional, diagnostic, observational study and multivariable logistic regression analysis for item selection.Setting8 hospitals in the Northern part of the Netherlands situated in the catchment area of a specialized movement disorder centre.Participants259 consecutive PD patients not yet on AT visiting the outpatient clinic of participating hospitals from February 2017 to July 2018.Predictors24 patient and disease characteristics as assessed by the treating neurologists, and scores on the NMS questionnaire.OutcomeApparent eligibility for referral for AT based on consensus by a panel of 5 experts in the field of AT.Results17 patients were deemed eligible for referral for AT (point prevalence: 6.6%). Presence of response fluctuations and troublesome dyskinesias were the strongest independent predictors of being eligible for referral. Both variables were included in the final model, as well as levodopa equivalent daily dose. Decision curve analysis showed that the new model outperformed the 5-2-1 criteria. A simple chart was constructed to provide guidance for referral. Discrimination of this simplified scoring system was good (AUC after bootstrapping: 0.97).ConclusionThe screening tool may improve efficiency of referral and subsequent treatment with AT in patients with PD. External validation is required prior to application in daily practice.Anyone who wishes to share, reuse, remix, or adapt this material must obtain permission from the corresponding author.
Analysis of 200,000 exome-sequenced UK Biobank subjects implicates genes involved in increased and decreased risk of hypertension
Authors: Curtis David 
Published: February 2021

AbstractBackgroundPrevious analyses have identified common variants along with some specific genes and rare variants which are associated with risk of hypertension but much remains to be discovered.Methods and ResultsExome-sequenced UK Biobank participants were phenotyped based on having a diagnosis of hypertension or taking anti-hypertensive medication to produce a sample of 66,123 cases and 134,504 controls. Variants with minor allele frequency (MAF) < 0.01 were subjected to a gene-wise weighted burden analysis, with higher weights assigned to variants which are rarer and/or predicted to have more severe effects. Of 20,384 genes analysed, two genes were exome-wide significant,DNMT3AandFES. Also strongly implicated wereGUCY1A1andGUCY1B1, which code for the subunits of soluble guanylate cyclase. There was further support for the previously reported effects of variants inNPR1and protective effects of variants inDBH. An inframe deletion inCACNA1Dwith MAF = 0.005, rs72556363, is associated with modestly increased risk of hypertension. Other biologically plausible genes highlighted consist ofCSK, AGTR1, ZYXandPREP. All variants implicated were rare and cumulatively they are not predicted to make a large contribution to the population risk of hypertension.ConclusionsThis approach confirms and clarifies previously reported findings and also offers novel insights into biological processes influencing hypertension risk, potentially facilitating the development of improved therapeutic interventions. This research has been conducted using the UK Biobank Resource.
Antigen-based multiplex strategies to discriminate SARS-CoV-2 natural and vaccine induced immunity from seasonal human coronavirus humoral responses
Authors: Laing Eric D. , Sterling Spencer L. , Richard Stephanie A. , Epsi Nusrat J. , Coggins Si’Ana , Samuels Emily C. , Phogat Shreshta , Yan Lianying , Moreno Nicole , Coles Christian L. , Drew Matthew , Mehalko Jennifer , English Caroline E. , Merritt Scott , Mende Katrin , Munster Vincent J. , Wit Emmie de , Chung Kevin K. , Millar Eugene V. , Tribble David R. , Simons Mark P. , Pollett Simon D. , Agan Brian K. , Esposito Dominic , Lanteri Charlotte , Clifton G. Travis , Mitre Edward , Burgess Timothy H. , Broder Christopher C. 
Published: February 2021

ABSTRACTSensitive and specific SARS-CoV-2 antibody assays remain critical for community and hospital-based SARS-CoV-2 sero-surveillance. With the rollout of SARS-CoV-2 vaccines, such assays must be able to distinguish vaccine from natural immunity to SARS-CoV-2 and related human coronaviruses. Here, we developed and implemented multiplex microsphere-based immunoassay strategies for COVD-19 antibody studies that incorporates spike protein trimers of SARS-CoV-2 and the endemic seasonal human coronaviruses (HCoV), enabling high throughout measurement of pre-existing cross-reactive antibodies. We varied SARS-CoV-2 antigen compositions within the multiplex assay, allowing direct comparisons of the effects of spike protein, receptor-binding domain protein (RBD) and nucleocapsid protein (NP) based SARS-CoV-2 antibody detection. Multiplex immunoassay performance characteristics are antigen-dependent, and sensitivities and specificities range 92-99% and 94-100%, respectively, for human subject samples collected as early as 7-10 days from symptom onset. SARS-CoV-2 spike and RBD had a strong correlative relationship for the detection of IgG. Correlation between detectable IgG reactive with spike and NP also had strong relationship, however, several PCR-positive and spike IgG-positive serum samples were NP IgG-negative. This spike and NP multiplex immunoassay has the potential to be useful for differentiation between vaccination and natural infection induced antibody responses. We also assessed the induction ofde novoSARS-CoV-2 IgG cross reactions with SARS-CoV and MERS-CoV spike proteins. Furthermore, multiplex immunoassays that incorporate spike proteins of SARS-CoV-2 and HCoVs will permit investigations into the influence of HCoV antibodies on COVID-19 clinical outcomes and SARS-CoV-2 antibody durability.
Outcomes of COVID-19 among Patients with End Stage Renal Disease on Remdesivir
Authors: Selvaraj Vijairam , Baig Muhammad , Dapaah-Afriyie Kwame , Finn Arkadiy , Jindal Atin , Bayliss George 
Published: February 2021

ABSTRACTBACKGROUNDSince the beginning of the COVID-19 pandemic, there has been widespread use of remdesivir in adults and children. There is little known information about its outcomes in patients with severe renal dysfunction or end-stage renal disease who are on hemodialysis.METHODSA retrospective, multicenter study was conducted on patients with end-stage renal disease on hemodialysis that were discharged after treatment for COVID-19 between April 1st and December 31st, 2020. Primary endpoints were the length of stay, mortality, maximum oxygen requirements along with the escalation of care needing mechanical ventilation. Secondary endpoints included change in C reactive protein, d dimer levels, and disposition.RESULTSA total of 52 charts were reviewed, of which 28 met the inclusion criteria. 14 patients received remdesivir, and 14 patients did not receive remdesivir. The majority of patients were caucasian, female, with diabetes mellitus and hypertension. The mean age was 65.33 +14.14 years. All the patients in the remdesivir group received dexamethasone as compared to only 30% of patients in the non-remdesivir group. There was no significant difference in C reactive protein, d dimer levels, and disposition between the two groups. Approximately 35% of the patients died, 18% required intensive ventilation, and the mean length of stay was 12.21 days.DISCUSSIONThe study demonstrated no clinically significant difference in length of stay, maximum oxygen requirements, or mortality in COVID-19 patients with end-stage renal disease in the remdesivir group as compared to the non-remdesivir group. Further studies are needed to study the effects of remdesivir on the renal function and disease course in patients with chronic kidney disease stage 4 or 5 that are not on dialysis.
Is Covid-19 seroprevalence different in health care workers as per their risk of exposure? A study from a tertiary care hospital in National Capital Region of India
Authors: Kataria Sushila , Phogat Rashmi , Sharma Pooja , Deswal Vikas , Alam Sazid , Singh Manish , Kumar Kuldeep , Gupta Vaibhav , Singh Padam , Dutt Rohit , Sarma Smita , Saxena Renu , Trehan Naresh 
Published: February 2021

AbstractBackgroundSARS-CoV-2 infection has severely ravaged health systems, economic and social progress globally in 2020. Seroprevalence studies can provide relevant information on the target populations for vaccination. They are relevant not only in the community, but also for critical population subgroups such as nursing homes or health care facilities. They will assist in strategizing the vaccination policy especially since there is limited availability of the vaccine and vaccine hesitancyObjectiveTo evaluate the seroprevalence in Health Care Workers (HCW) at our hospital and to identify parameters which may affect it.MethodologyThe Baseline profiling and seroprevalence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) was assessed among 3258 healthcare workers (HCWs) of Medanta-The Medicity, Gurugram, Haryana, India, as a part of an ongoing cohort study.The fully automated LIAISON® SARS-CoV-2 S1/S2 IgG test using the chemiluminescence immunoassay (CLIA) for the quantitative determination of anti-S1 and anti-S2 specific IgG antibodies to SARS-CoV-2 was used to test serum samples collected before the receipt of the vaccine. Seroprevalence was evaluated as per gender, age, association with previous Covid-19 diagnosis, use of supplements, and role in the hospital and type of exposure.ResultsOf the 3258 participants tested for IgG serology (S1 and S2 proteins) 46.2% (CI 44.4 – 47.9%) were positive (i.e. had an antibody titre more than 15 Au/ml). Higher seroprevalence was seen in the ‘others’ ie non clinical health care workers (including management, research personnel, pharmacists, technicians, general duty staff, housekeeping, security, food and beverage, and facility maintenance teams) (50.2 Au/ml) than that in clinical HCW (ie doctors and nurses)where it was significantly lower (41.4 Au/ml, p= 0.0001). Also, people with history of Covid-19 were found to have significantly higher antibody levels (p = 0.0001). Amongst the healthcare workers, doctors and nurses had higher relative risk of acquiring Covid-19 infection (RR = 1.21; 95% C.I.: 1.12 - 1.31).ConclusionSeroprevalence in healthcare workers at our hospital is high at 46.2%. It is higher in non-clinical HCW than in clinical HCW. The risk of acquiring Covid-19 infection was higher in clinical HCW and thus, this subgroup may benefit most from vaccination. History of Covid-19 may provide double the protection, in particular in those who had it recently.
Data-driven analysis of COVID-19 reveals specific severity patterns distinct from the temporal immune response
Authors: Lim Jackwee , Puan Kia Joo , Wang Liang Wei , Weng Teng Karen Wei , Loh Chiew Yee , Tan Kim Peng , Carissimo Guillaume , Chan Yi-Hao , Poh Chek Meng , Lee Cheryl Yi-Pin , Fong Siew-Wai , Yeo Nicholas Kim-Wah , Chee Rhonda Sin-Ling , Amrun Siti Naqiah , Chang Zi Wei , Tay Matthew Zirui , Torres-Ruesta Anthony , Fernandez Norman Leo , How Wilson , Andiappan Anand K. , Lee Wendy , Duan Kaibo , Tan Seow-Yen , Yan Gabriel , Kalimuddin Shirin , Lye David Chien , Leo Yee-Sin , Ong Sean W. X. , Young Barnaby E. , Renia Laurent , Ng Lisa F.P. , Lee Bernett , Rötzschke Olaf 
Published: February 2021

AbstractKey immune signatures of SARS-CoV-2 infection may associate with either adverse immune reactions (severity) or simply an ongoing anti-viral response (temporality); how immune signatures contribute to severe manifestations and/or temporal progression of disease and whether longer disease duration correlates with severity remain unknown. Patient blood was comprehensively immunophenotyped via mass cytometry and multiplex cytokine arrays, leading to the identification of 327 basic subsets that were further stratified into more than 5000 immunotypes and correlated with 28 plasma cytokines. Low-density neutrophil abundance was closely correlated with hepatocyte growth factor levels, which in turn correlated with disease severity. Deep analysis also revealed additional players, namely conventional type 2 dendritic cells, natural killer T cells, plasmablasts and CD16+monocytes, that can influence COVID-19 severity independent of temporal progression. Herein, we provide interactive network analysis and data visualization tools to facilitate data mining and hypothesis generation for elucidating COVID-19 pathogenesis.
Population Age-Ineligible for COVID-19 Vaccine in the United States: Implications for State, County, and Race/Ethnicity Vaccination Targets
Authors: Pathak Elizabeth B. , Menard Janelle , Garcia Rebecca 
Published: February 2021

ABSTRACTBackgroundWe examined the geographic and racial/ethnic distribution of the SARS-CoV-2 vaccine age-ineligible population (0-15 years old) in the U.S., and calculated the proportion of the age-eligible population that will need to be vaccinated in a given geo-demographic group in order to achieve either 60% or 75% vaccine coverage for that population as a whole.MethodsUS Census Bureau population estimates for 2019 were used to calculate the percent vaccine ineligible and related measures for counties, states, and the nation as a whole. Vaccination targets for the 30 largest counties by population were calculated. Study measures were calculated for racial/ethnic populations at the national (n=7) and state (n=6) levels.ResultsPercent of population ineligible for vaccine varied widely both geographically and by race/ethnicity. State values ranged from 15.8% in Vermont to 25.7% in Utah, while percent ineligible of the major racial/ethnic groups was 16.4% of non-Hispanic whites, 21.6% of non-Hispanic Blacks, and 27.5% of Hispanics. Achievement of total population vaccine coverage of at least 75% will require vaccinating more than 90% of the population aged 16 years and older in 29 out of 30 of the largest counties in the U.S.ConclusionsThe vaccine-ineligibility of most children for the next 1-2 years, coupled with reported pervasive vaccine hesitancy among adults, especially women and most minorities, means that achievement of adequate levels of vaccine coverage will be very difficult for many vulnerable geographic areas and for several racial/ethnic minority groups, particularly Hispanics, Blacks, and American Indians.
Identification of phenotype-specific networks from paired gene expression-cell shape imaging data
Authors: Barker Charlie George , Petsalaki Eirini , Giudice Girolamo , Sero Julia , Ekpenyong Emmanuel Nsa , Bakal Chris , Petsalaki Evangelia 
Published: February 2021

AbstractThe morphology of breast cancer cells is often used as an indicator of tumour severity and prognosis. Additionally, morphology can be used to identify more fine-grained, molecular developments within a cancer cell, such as transcriptomic changes and signaling pathway activity. Delineating the interface between morphology and signaling is important to understand the mechanical cues that a cell processes in order to undergo epithelial-to-mesenchymal transition and consequently metastasize. However, the exact regulatory systems that define these changes remain poorly characterised. In this study, we employ a network-systems approach to integrate imaging data and RNA-seq expression data. Our workflow allows the discovery of unbiased and context-specific gene expression signatures and cell signaling sub-networks relevant to the regulation of cell shape, rather than focusing on the identification of previously known, but not always representative, pathways. By constructing a cell-shape signaling network from shape-correlated gene expression modules and their upstream regulators, we found central roles for developmental pathways such as WNT and Notch as well as evidence for the fine control of NFkB signaling by numerous kinase and transcriptional regulators. Further analysis of our network implicates a gene expression module enriched in the RAP1 signaling pathway as a mediator between the sensing of mechanical stimuli and regulation of NFkB activity, with specific relevance to cell shape in breast cancer.
REAP: A platform to identify autoantibodies that target the human exoproteome
Authors: Wang Eric Y. , Dai Yile , Rosen Connor E. , Schmitt Monica M. , Dong Mei X. , Ferré Elise M. N. , Liu Feimei , Yang Yi , Gonzalez-Hernandez Jaime A. , Meffre Eric , Hinchcliffe Monique , Koumpouras Fotios , Lionakis Michail S. , Ring Aaron M. 
Published: February 2021

AbstractAutoantibodies that recognize extracellular proteins (the “exoproteome”) exert potent biological effects but have proven challenging to detect with existing screening technologies. Here, we developed Rapid Extracellular Antigen Profiling (REAP) as a technique for comprehensive, high-throughput discovery of exoproteome-targeting autoantibodies. With REAP, patient samples are applied to a genetically-barcoded library containing 2,688 human extracellular proteins displayed on the surface of yeast. Antibody-coated cells are isolated by magnetic selection and deep sequencing of their barcodes is used to identify the displayed antigens. To benchmark the performance of REAP, we screened 77 patients with autoimmune polyendocrinopathy candidiasis ectodermal dystrophy (APECED). REAP sensitively and specifically detected known autoantibody reactivities in APECED in addition to numerous previously unidentified reactivities. We further screened 106 patients with systemic lupus erythematosus (SLE) and identified novel autoantibody reactivities against a diverse set of antigens including growth factors, extracellular matrix components, cytokines, and immunomodulatory proteins. Several of these responses were associated with disease severity and specific clinical manifestations of SLE and exerted potent functional effects on cell signalingex vivo. These findings demonstrate the utility of REAP to atlas the expansive landscape of exoproteome-targeting autoantibodies and their impacts on patient health outcomes.
Feedforward ribosome control mitigates gene activation burden
Authors: Barajas Carlos , Huang Hsin-Ho , Gibson Jesse , Sandoval Luis , Del Vecchio Domitilla 
Published: February 2021

AbstractHeterologous gene activation causes non-physiological burden on cellular resources that cells are unable to adjust to. Here, we introduce a feedforward controller that increases ribosome level upon activation of a gene of interest (GOI) to compensate for such a burden. The controller achieves this by activating a modified SpoT enzyme with sole hydrolysis activity, which lowers ppGpp level and thus de-represses ribosomes. Without the controller, activation of the GOI decreased growth rate by more than 50%. With the controller, we could activate the GOI to the same level without a growth rate decrease. A cell strain armed with the controller in co-culture enabled persistent population-level activation of a GOI, which could not be achieved by a strain devoid of the controller. The feedforward controller is a tunable, modular, and portable tool that for the first time allows dynamic gene activation without growth rate defects for bacterial synthetic biology applications.
Stress induced Differential Expression of THAP9 & THAP9-AS1 in the S-phase of cell cycle
Authors: Sharma Vasudha , Thakore Prachi , Krishnan Meena , Majumdar Sharmistha 
Published: February 2021

AbstractTransposable elements function as one of the major effectors in response to biological or environmental stress. Under normal conditions, host organisms deploy epigenetic and post-transcriptional machinery (histone modifications, chromatin remodelers, long non-coding RNAs (lncRNAs)) at the TE sites to contain their mobility. But many a times, the chromatin architecture undergoes TE induced changes under the effect of stress that in turn might lead to unprecedented gene expression. LncRNAs are emerging as a crucial tool in the regulation of TEs. TEs possess remarkable abilities to respond in the face of stress, ranging from undetected mutations to changing the regulatory landscape of the host. Although the relationship between stress response and TE activation/deactivation is well acknowledged but our understanding of the mechanism of regulation remains poor.This study focuses on the gene expression of THAP9, a domesticated transposon and lncRNA THAP9-AS1 (THAP9-anti sense1), which form a sense and anti-sense gene pair with a promoter overlap of approximately 350bp. The two genes exhibit different patterns of gene expression under different types of stresses in the S-phase of the cell cycle. THAP9-AS1 is always upregulated under stress whereas THAP9 exhibits both downregulation and upregulation in different stresses. Both THAP9 and THAP9-AS1 exhibit a periodic gene expression throughout the S-phase which is a characteristic of cell cycle regulated genes.