bluuebunny/crossref_metadata_2025_split huggingface dataset:
Cancer risk perception and knowledge and physician communication behaviors: specific influences on cervical cancer and colorectal cancer screening in women 50-65 years old
Authors: Harper Diane M , Tariq Madiha , Alhawli Asraa , Syed Nadia , Patel Minal R , Resnicow Ken 
Published: May 2021

AbstractBackgroundWomen 50-65 years old have the lowest cervical and colorectal cancer (CRC) screening rates amongst ages recommended for screening. The primary aim of this work is to determine how cancer risk perceptions and provider communication behaviors, in addition to known demographic factors, influence the uptake of both cervical and CRC screening or a single screen among women in southeast Michigan.Methods14 health services and communication behavior questions were adapted from the Health Information National Trends Survey (HINTS) and administered to a multiethnic sample of adults in southeast Michigan. The outcome variable was self-reported up to date cervical and/or CRC screening as defined by the United States Preventive Services Task Force (USPSTF). Demographic and cancer risk/communication behavior responses of the four screening status categories (both tests, one test, no tests) were analyzed with multinomial regression for all comparisons.ResultsOf the 394 respondents, 54% were up to date for both cervical and CRC screening, 21% were up to date with only cervical cancer screening and 12% were up to date for only CRC screening. Of the 14 risk perception and communication behaviors only, Did your primary care physician (PCP) involve you in the decisions about your health care as much as you wanted? was significantly associated with women having both screens compared to only cervical cancer screening (aOR 1.67 (95% CI: 1.08, 2.57). The control variables included in the model, also significant, were MENA and Black races compared to white women and age.ConclusionsScreening behavior for both cancers is different than a single screen and associated with the woman’s perception of the physician involving her in her care as much as she wanted. In addition, educational programs are needed for MENA women.
Evidence-to-decision frameworks: a review and analysis to inform decision-making for environmental health interventions
Authors: Norris Susan L. , Aung Max T. , Chartres Nicholas , Woodruff Tracey J. 
Published: May 2021

AbstractBackgroundEvidence-to-decision (EtD) frameworks provide a structured and transparent approach for groups of experts to use when formulating recommendations or making decisions. While extensively used for clinical and public health recommendations, EtD frameworks are not in widespread use in environmental health.ObjectivesThis review sought to identify, compare and contrast key EtD frameworks for decisions or recommendations on interventions used in clinical medicine, public health or environmental health. Our goal was to identify best practices and guidance which will be used to inform the development of an EtD framework for formulating recommendations regarding interventions to prevent or mitigate the harmful effects of exposure to substances in the environment.MethodsWe identified a convenience sample of EtD frameworks used by a range of organizations. We searched Medline for systematic reviews of EtD frameworks used in clinical medicine, and public or environmental health. In a qualitative manner, we summarized the decision criteria in the selected frameworks and in the reviews.ResultsFourteen key organizations provided 18 EtD frameworks; most frameworks focused on clinical medicine or public health interventions; four focused on environmental health and three on economic considerations. Only one framework was based on an underlying conceptual model, and rarely was a systematic review of potential criteria performed during the frameworks development. GRADE encompasses a set of closely related frameworks for different types of decisions. Harms of interventions were examined in all frameworks and benefits in all but one. Other criteria included certainty of the body of evidence (15 frameworks), resource considerations (15), feasibility (13), equity (12), values (11), acceptability (11), and human rights (2). There was variation in how specific criteria were defined. The five identified systematic reviews reported a similar spectrum of EtD criteria.DiscussionThe EtD frameworks examined encompassed similar criteria, with tailoring to specific audience needs. However, there is variation in development processes, terminology, level of detail provided and presentation of the criteria. Existing frameworks are a useful starting point for development of one tailored to decision-making in environmental health.
Multi-site Evaluation of SARS-CoV-2 Spike Mutation Detection Using a Multiplex Real-time RT-PCR Assay
Authors: Bier Carolin , Edelmann Anke , Theil Kathrin , Schwarzer Rolf , Deichner Maria , Gessner Andre , Hiergeist Andreas , Rentschler Ute , Gohl Peter , Kuchta Alison , Manohar Chitra , Santini Chris , Duncan Dana , Canchola Jesse , Sun Jingtao , Spier Gene , Simon Christian 
Published: May 2021

ABSTRACTBackgroundSARS-CoV-2 causes COVID-19, which can be fatal and is responsible for a global pandemic. Variants with increased transmissibility or the potential to evade immunity have emerged and represent a threat to global pandemic control. Variants of concern (VOC) can be identified by sequencing of viral RNA, or by more rapid methods for detection of subsets of signature mutations.MethodsWe developed a multiplex, real-time RT-PCR assay (cobas®SARS-CoV-2 Variant Set 1) for the qualitative detection and differentiation of three key SARS-CoV-2 mutations in the viral spike protein: del 69-70, E484K and N501Y. Analytical sensitivity and accuracy were evaluated at three testing sites using clinical specimens from patients infected with SARS-CoV-2 variants belonging to several different lineages, including B.1.1.7, B.1.351, and P.1.ResultsThe limit of detection for E484K was between 180 and 620 IU/mL for the three different isolates tested. For N501Y, the LOD was between 270 and 720 IU/mL (five isolates), while for del 69-70, it was 80 - 92 IU/mL (two isolates). Valid test results were obtained with all clinical specimens that were positive using routine diagnostic tests. Compared to sequencing (Sanger and next-generation), test results were 100% concordant at all three loci; no false positive or false negative results were observed.ConclusionsData collected at three independent laboratories indicates excellent performance and concordance of cobas®SARS-CoV-2 Variant Set 1 with sequencing. New sets of primers and probes that target additional loci can be rapidly deployed in response to the identification of other emerging variants.
Identifying Cases of Shoulder Injury Related to Vaccine Administration (SIRVA) Using Natural Language Processing
Authors: Zheng Chengyi , Duffy Jonathan , Liu In-Lu Amy , Sy Lina S. , Navarro Ronald A. , Kim Sunhea S. , Ryan Denison , Chen Wansu , Qian Lei , Mercado Cheryl , Jacobsen Steven J. 
Published: May 2021

BackgroundShoulder injury related to vaccine administration (SIRVA) accounts for more than half of all claims received by the National Vaccine Injury Compensation Program. However, there is a lack of population-based studies due to the challenge of identifying SIRVA cases in large health care databases.ObjectiveTo develop a natural language processing (NLP) method to identify SIRVA cases from clinical notes.MethodsWe conducted the study among members of a large integrated health care organization who were vaccinated between 04/1/2016 and 12/31/2017 and had subsequent diagnosis codes indicative of shoulder injury. Based on a training dataset with a chart review reference standard of 164 individuals, we developed an NLP algorithm to extract shoulder disorder information, including prior vaccination, anatomic location, temporality and causality. The algorithm identified three groups of positive SIRVA cases (definite, probable and possible) based on the strength of evidence. We compared NLP results to a chart review reference standard of 100 vaccinated individuals. We then applied the final automated NLP algorithm to a broader cohort of vaccinated individuals with a shoulder injury diagnosis code and performed manual chart confirmation on a random sample of NLP-identified definite cases and all NLP-identified probable and possible cases.ResultsIn the validation sample, the NLP algorithm had 100% accuracy for identifying 4 SIRVA cases and 96 individuals without SIRVA. In the broader cohort of 53,585 individuals, the NLP algorithm identified 291 definite, 124 probable, and 52 possible SIRVA cases. The chart-confirmation rates for these groups were 95.3%, 67.7% and 18.9%, respectively.ConclusionsThe algorithm performed with high sensitivity and reasonable specificity in identifying positive SIRVA cases. The NLP algorithm can potentially be used in future population-based studies to identify this rare adverse event, avoiding labor-intensive chart review validation.
Influenza A M2 recruits M1 to the plasma membrane: a fluorescence fluctuation microscopy study
Authors: Petrich Annett , Dunsing Valentin , Bobone Sara , Chiantia Salvatore 
Published: May 2021

AbstractInfluenza A virus (IAV) is a respiratory pathogen that causes seasonal epidemics with significant mortality. One of the most abundant proteins in IAV particles is the matrix protein 1 (M1), which is essential for the virus structural stability. M1 organizes virion assembly and budding at the plasma membrane (PM), where it interacts with other viral components. The recruitment of M1 to the PM as well as its interaction with the other viral envelope proteins (hemagglutinin (HA), neuraminidase, matrix protein 2 (M2)) is controversially discussed in previous studies. Therefore, we used fluorescence fluctuation microscopy techniques (i.e., scanning fluorescence cross-correlation spectroscopy and Number and Brightness) to quantify the oligomeric state of M1 and its interactions with other viral proteins in co-transfected as well as infected cells. Our results indicate that M1 is recruited to the PM by M2, as a consequence of the strong interaction between the two proteins. In contrast, only a weak interaction between M1 and HA was observed. M1-HA interaction occurred only in the case that M1 was already bound to the PM. We therefore conclude that M2 initiates the assembly of IAV by recruiting M1 to the PM, possibly allowing its further interaction with other viral proteins.Statement of SignificanceInfluenza A virus (IAV) is a pathogen responsible for epidemics and occasional pandemics and, therefore, a significant burden on health systems. To develop innovative therapeutic approaches, a deeper understanding of the viral replication cycle is needed. For example, during the formation of new virions in infected cells, several viral components must assemble at the plasma membrane, but the molecular interactions involved in this process are not clearly understood. In this work, we use quantitative fluorescence microscopy methods to monitor the interplay between several viral proteins in live cell models. Our results underline the importance of the interactions between two specific proteins (M1 and M2) and shed light on the first steps in IAV assembly.
Multiple mechanisms for overcoming lethal over-initiation of DNA replication
Authors: Anderson Mary E. , Smith Janet L. , Grossman Alan D. 
Published: May 2021

AbstractDNA replication is a highly regulated process that is primarily controlled at the step of initiation. In the gram-positive bacteriumBacillus subtilisthe replication initiator DnaA, is regulated by YabA, which inhibits cooperative binding at the origin. Mutants lacking YabA have increased and asynchronous initiation. We found that under conditions of rapid growth, thednaA1mutation that causes replication over-initiation, was synthetic lethal with a deletion ofyabA. We isolated several classes of suppressors of the lethal phenotype of the ΔyabA dnaA1double mutant. Some suppressors (dnaC, cshA) caused a decrease in replication initiation. Others (relA, nrdR) stimulate replication elongation. One class of suppressors decreased levels of the replicative helicase, DnaC, thereby limiting replication initiation. We found that decreased levels of helicase were sufficient to decrease replication initiation under fast growth conditions. Our results highlight the multiple mechanisms cells use to regulate DNA replication.
Extracting spatial networks from capture-recapture data reveal structured habitat use within a marine mammal’s spatial range
Authors: Bonnell Tyler R. , Michaud Robert , Dupuch Angélique , Lesage Véronique , Chion Clément 
Published: May 2021

AbstractEstimating the impacts of anthropogenic disturbances requires an understanding of the habitat use patterns of individuals within a population. This is especially the case when disturbances are localized within a population’s spatial range, as variation in habitat-use within a population can drastically alter the distribution of impacts.Here, we illustrate the potential for multilevel multinomial models to generate spatial networks from capture-recapture data, a common data source use in wildlife studies to monitor population dynamics and habitat use. These spatial networks capture which regions of a population’s spatial distribution share similar/dissimilar individual usage patterns, and can be especially useful for detecting structured habitat use within the population’s spatial range.Using simulations and 18 years of capture-recapture data from St. Lawrence Estuary (SLE) beluga, we show that this approach can successfully estimate the magnitude of similarities/dissimilarities in individual usage patterns across sectors, and identify sectors that share similar individual usage patterns that differ from other sectors, i.e., structured habitat use. In the case of SLE beluga, this method identified multiple clusters of individuals, each preferentially using restricted areas within their summer range of the SLE.Synthesis and applications.Multilevel multinomial models can be effective at estimating spatial structure in habitat use within wildlife populations sampled by capture-recapture of individuals. Our finding of a structured habitat use within the SLE beluga summer range has direct implications for estimating individual exposures to localized stressors, such as underwater noise from shipping or other activities.
Single Nuclei Sequencing of Human Putamen Oligodendrocytes Reveals Altered Heterogeneity and Disease-Associated Changes in Parkinson’s Disease and Multiple System Atrophy
Authors: Teeple Erin , Joshi Pooja , Pande Rahul , Huang Yinyin , Karambe Akshat , Latta-Mahieu Martine , Sardi S. Pablo , Cedazo-Minguez Angel , Klinger Katherine W. , Flores-Morales Amilcar , Madden Stephen L. , Rajpal Deepak , Kumar Dinesh 
Published: May 2021

AbstractThe role of oligodendrocytes in neurodegenerative diseases remains incompletely understood and largely unexplored at the single cell level. We profiled 87,086 single nuclei from human brain putamen region for healthy control, Parkinson’s Disease (PD), and Multiple System Atrophy (MSA). Oligodendrocyte lineage cells were the dominant cell-type in the putamen with oligodendrocyte subpopulations clustered by transcriptomic variation found to exhibit diverse functional enrichment patterns, and this oligodendrocyte heterogeneity was altered in a disease-specific way. Among profiled oligodendrocyte subpopulations, differences in expression of SNCA, HAPLN2, MAPT, APP, and OPALIN were observed for PD and MSA compared with healthy controls. Intriguingly, greater activation of unfolded protein response pathway gene expression was observed in PD nuclei versus MSA. Using network analysis, we then identified specific PD- and MSA-correlated gene co-expression modules enriched with disease relevant pathways; the PD-correlated module was significantly enriched for Parkinson’s Disease GWAS loci (p = 0.01046). Our analysis provides a broader understanding of oligodendrocyte heterogeneity and reveals distinctive oligodendrocyte pathological alterations associated with PD and MSA which may suggest potential novel therapeutic targets and new strategies for disease modification.
Subpopulations of neurons in lOFC encode previous and current rewards at time of choice
Authors: Hocker David , Brody Carlos D. , Savin Cristina , Constantinople Christine M 
Published: May 2021

1AbstractStudies of neural dynamics in lateral orbitofrontal cortex (lOFC) have shown that subsets of neurons that encode distinct aspects of behavior, such as value, may project to common downstream targets. However, it is unclear whether reward history, which may subserve lOFC’s well-documented role in learning, is represented by functional subpopulations in lOFC. Previously, we analyzed neural recordings from rats performing a value-based decision-making task, and we documented trial-by-trial learning that required lOFC (Constantinopleet al., 2019). Here we characterize functional subpopulations of lOFC neurons during behavior, including their encoding of task variables. We found five distinct clusters of lOFC neurons, either based on clustering of their trial-averaged peristimulus time histograms (PSTHs), or a feature space defined by their average conditional firing rates aligned to different task variables. We observed weak encoding of reward attributes, but stronger encoding of reward history, the animal’s left or right choice, and reward receipt across all clusters. Only one cluster, however, encoded the animal’s reward history at the time shortly preceding the choice, suggesting a possible role in integrating previous and current trial outcomes at the time of choice. This cluster also exhibits qualitatively similar responses to identified corticostriatal projection neurons in a recent study (Hirokawaet al., 2019), and suggests a possible role for subpopulations of lOFC neurons in mediating trial-by-trial learning.
Palbociclib-mediated cell cycle arrest can occur in the absence of the CDK inhibitors p21 and p27
Authors: Pennycook Betheney R. , Barr Alexis R. 
Published: May 2021

AbstractThe use of CDK4/6 inhibitors in the treatment of a wide range of cancers is an area of ongoing investigation. Despite their increasing clinical use, there is limited understanding of the determinants of sensitivity and resistance to these drugs. Recent data has cast doubt on how CDK4/6 inhibitors arrest proliferation, provoking renewed interest in the role(s) of CDK4/6 in driving cell proliferation. As the use of CDK4/6 inhibitors in cancer therapies becomes more prominent, an understanding of their effect on the cell cycle becomes more urgent. Here, we investigate the mechanism of action of CDK4/6 inhibitors in promoting cell cycle arrest. Two main models explain how CDK4/6 inhibitors cause G1 cell cycle arrest, which differ in their dependence on the CDK inhibitor proteins p21 and p27. We have used live and fixed single-cell quantitative imaging, with inducible degradation systems, to address the roles of p21 and p27 in the mechanism of action of CDK4/6 inhibitors. We find that CDK4/6 inhibitors can initiate and maintain a cell cycle arrest without p21 or p27. This work clarifies our current understanding of the mechanism of action of CDK4/6 inhibitors and has implications for cancer treatment and patient stratification.
Ca2+-mediated higher-order assembly of b0,+AT–rBAT is a key step for system b0,+biogenesis and cystinuria
Authors: Lee Yongchan , Wiriyasermkul Pattama , Moriyama Satomi , Mills Deryck J. , Kühlbrandt Werner , Nagamori Shushi 
Published: May 2021

AbstractCystinuria is a genetic disorder characterized by overexcretion of dibasic amino acids and cystine, which causes recurrent kidney stones and occasionally severe kidney failure. Mutations of the two responsible proteins, rBAT and b0,+AT, which comprise system b0,+, are linked to type I and non-type I cystinuria respectively and they exhibit distinct phenotypes due to protein trafficking defects or catalytic inactivation. Although recent structural insights into human b0,+AT–rBAT suggested a model for transport-inactivating mutations, the mechanisms by which type I mutations trigger trafficking deficiencies are not well understood. Here, using electron cryo-microscopy and biochemistry, we discover that Ca2+-mediated higher-order assembly of system b0,+is the key to its trafficking on the cell surface. We show that Ca2+stabilizes the interface between two rBAT molecules to mediate super-dimerization, and this in turn facilitates the N-glycan maturation of system b0,+. A common cystinuria mutant T216M and mutations that disrupt the Ca2+site in rBAT cause the loss of higher-order assemblies, resulting in protein trafficking deficiency. Mutations at the super-dimer interface reproduce the mis-trafficking phenotype, demonstrating that super-dimerization is essential for cellular function. Cell-based transport assays confirmed the importance of the Ca2+site and super-dimerization, and additionally suggested which residues are involved in cationic amino acid recognition. Taken together, our results provide the molecular basis of type I cystinuria and serve as a guide to develop new therapeutic strategies against it. More broadly, our findings reveal an unprecedented link between transporter oligomeric assembly and trafficking diseases in general.
Fixel-Based Analysis and Free Water Corrected DTI Evaluation of HIV Associated Neurocognitive Disorders
Authors: Finkelstein Alan , Faiyaz Abrar , Weber Miriam T. , Qiu Xing , Uddin Md Nasir , Zhong Jianhui , Schifitto Giovanni 
Published: May 2021

AbstractWhite matter damage is a consistent finding in HIV infected (HIV+) individuals. Previous studies have evaluated WM fiber tract specific brain regions in HIV-associated neurocognitive disorders using diffusion tensor imaging (DTI). However, DTI might lack an accurate biological interpretation, and the technique suffers from several limitations. Here, we sought to evaluate Fixel-based analysis (FBA) and free water corrected DTI (fwcDTI) metrics between HIV+ and HIV uninfected (HIV−) individuals, and their relationships with blood markers and cognitive scores. We also compared the specificity of both MRI metrics in their ability to distinguish between individuals with and without cognitive impairment using machine learning classifiers. Using 94 age-matched participants, we found that whole brain FBA was significantly reduced (up to 15%) in various fiber bundles. Tract based special statistics (TBSS) of fwcDTI metrics revealed decreased fractional anisotropy FAT(by 1-2%) in HIV+ compared to HIV− individuals in areas consistent with those observed in FBA, but these were not significant. An adaptive boosting classifier reliably distinguished between cognitively normal patients and those with cognitive impairment with 80% precision and 78% recall. Therefore, FBA may serve as a potential in-vivo biomarker for evaluating and monitoring axonal degeneration in HIV+ patients at risk for neurocognitive impairment.
Generalizing predictions to unseen sequencing profiles via deep generative models
Authors: Oh Min , Zhang Liqing 
Published: May 2021

AbstractPredictive models trained on sequencing profiles often fail to achieve expected performance when externally validated on unseen profiles. While many factors such as batch effects, small data sets, and technical errors contribute to the gap between source and unseen data distributions, it is a challenging problem to generalize the predictive models across studies without any prior knowledge of the unseen data distribution. Here, this study proposes DeepBioGen, a sequencing profile augmentation procedure that characterizes visual patterns of sequencing profiles, generates realistic profiles based on a deep generative model capturing the patterns, and generalizes the subsequent classifiers. DeepBioGen outperforms other methods in terms of enhancing the generalizability of the prediction models on unseen data. The generalized classifiers surpass the state-of-the-art method, evaluated on RNA sequencing tumor expression profiles for anti-PD1 therapy response prediction and WGS human gut microbiome profiles for type 2 diabetes diagnosis.