bluuebunny/crossref_metadata_2025_split huggingface dataset:
“I had made the decision, and no one was going to stop me” —Facilitators of PrEP adherence during pregnancy and postpartum in Cape Town, South Africa
Authors: Davey Dvora L. Joseph , Knight Lucia , Markt-Maloney Jackie , Tsawe Nokwazi , Gomba Yolanda , Mashele Nyiko , Dovel Kathryn , Gorbach Pamina , Bekker Linda-Gail , Coates Thomas J. , Myer Landon 
Published: November 2020

AbstractIntroductionHIV incidence is high during pregnancy and postpartum in many settings. PrEP is safe and effective but requires adherence during potential HIV exposure, yet the facilitators of high maternal adherence are not well understood in high HIV burden settings.MethodsWe conducted semi-structured interviews with women who reported high adherence (PrEP use ≥ 25 days in last 30-days) within a PrEP service for pregnant and postpartum women located in a large primary care facility in a high-HIV burden township. Topics for interviews included: individual/interpersonal risk, disclosure, anticipated PrEP stigma, safety, side-effects, and facility-level factors effecting adherence. A thematic approach guided an iterative process of coding (reviewed to ensure intercoder reliability) and analysis using NVivo 12.ResultsWe interviewed 25 postpartum women with high PrEP adherence who were on PrEP for a median of 9-months, median age 26-years, and median baseline gestational age 24-weeks. Themes identified as key drivers of optimal PrEP use were HIV risk perception – primarily due to partner’s perceived risky sexual behaviors and unknown serosatus—and a strong desire to have a baby free of HIV. Reported disclosure of PrEP use to family, partners and friends facilitated PrEP adherence. Women continued PrEP postpartum because they felt empowered by PrEP and did not want to “go backwards” and increase their HIV risk as before PrEP. Women who reported high adherence all discussed having community support and reminders to take PrEP on time. The primary barriers were anticipated or experienced stigma, which most overcame through education of partners/family about PrEP. Pregnant women experienced transient side effects, but found ways to continue, including taking PrEP at night. Women believed PrEP education and counselling were accessible when integrated into antenatal care which contributed to continued PrEP use.ConclusionsFacilitators of optimal PrEP use through pregnancy and postpartum included fear of HIV acquisition for self and infant, mostly due to partner sexual behaviors and unknown serostatus, along with PrEP disclosure, and encouragement from partners and family. PrEP programs for pregnant and postpartum women should integrate strategies to assist women with realistic appraisals of risk and teach skills for securing support for significant others.
Integrated Protein Network Analysis of Whole Exome Sequencing of Severe Preeclampsia
Authors: Schuster Jessica , Tollefson George A. , Zarate Valeria , Agudelo Anthony , Stabila Joan , Ragavendran Ashok , Padbury James , Uzun Alper 
Published: November 2020

AbstractPreeclampsia is a hypertensive disorder of pregnancy, which complicates up to 15 % of US deliveries. It is an idiopathic disorder with complex disease genetics associated with several different phenotypes. We sought to determine if the genetic architecture of preeclampsia can be described by clusters of patients with variants in genes in shared protein interaction networks. We performed a case-control study using whole exome sequencing on early onset preeclamptic mothers with severe features and control mothers with uncomplicated pregnancies. The study was conducted at Women & Infants Hospital of Rhode Island (WIH). A total of 143 patients were enrolled, 61 women with early onset preeclampsia with severe features based on ACOG criteria, and 82 control women at term, matched for race and ethnicity. The main outcomes are variants associated with severe preeclampsia and demonstration of the genetic architecture of preeclampsia. A network analysis and visualization tool, Proteinarium, was used to confirm there are clusters of patients with shared gene networks associated with severe preeclampsia. The majority of the sequenced patients appear in two significant clusters. We identified one case dominant and one control dominant cluster. Thirteen genes were unique to the case dominated cluster. Among these genes, LAMB2, PTK2, RAC1, QSOX1, FN1, and VCAM1 have known associations with the pathogenic mechanisms of preeclampsia. Using the exome-wide sequence variants, combined with these 13 identified network genes, we generated a polygenetic risk score for severe preeclampsia with an AUC of 0.57. Using bioinformatic analysis, we were able to identify subsets of patients with shared protein interaction networks, thus confirming our hypothesis about the genetic architecture of preeclampsia. The unique genes identified in the cluster associated with severe preeclampsia were able to increase the predictive power of the polygenic risk score.
Cell-type Specific Expression Quantitative Trait Loci Associated with Alzheimer Disease in Blood and Brain Tissue
Authors: Patel Devanshi , Zhang Xiaoling , Farrell John J. , Chung Jaeyoon , Stein Thor D. , Lunetta Kathryn L. , Farrer Lindsay A. 
Published: November 2020

ABSTRACTBecause regulation of gene expression is heritable and context-dependent, we investigated AD-related gene expression patterns in cell-types in blood and brain. Cis-expression quantitative trait locus (eQTL) mapping was performed genome-wide in blood from 5,257 Framingham Heart Study (FHS) participants and in brain donated by 475 Religious Orders Study/Memory & Aging Project (ROSMAP) participants. The association of gene expression with genotypes for all cis SNPs within 1Mb of genes was evaluated using linear regression models for unrelated subjects and linear mixed models for related subjects. Cell type-specific eQTL (ct-eQTL) models included an interaction term for expression of “proxy” genes that discriminate particular cell type. Ct-eQTL analysis identified 11,649 and 2,533 additional significant gene-SNP eQTL pairs in brain and blood, respectively, that were not detected in generic eQTL analysis. Of note, 386 unique target eGenes of significant eQTLs shared between blood and brain were enriched in apoptosis and Wnt signaling pathways. Five of these shared genes are established AD loci. The potential importance and relevance to AD of significant results in myeloid cell-types is supported by the observation that a large portion of GWS ct-eQTLs map within 1Mb of established AD loci and 58% (23/40) of the most significant eGenes in these eQTLs have previously been implicated in AD. This study identified cell-type specific expression patterns for established and potentially novel AD genes, found additional evidence for the role of myeloid cells in AD risk, and discovered potential novel blood and brain AD biomarkers that highlight the importance of cell-type specific analysis.
COVID-19: Short term prediction model using daily incidence data
Authors: Zhao Hongwei , Merchant Naveed N , McNulty Alyssa , Radcliff Tiffany A , Cote Murray J , Fischer Rebecca , Sang Huiyan , Ory Marcia G 
Published: November 2020

AbstractBackgroundPrediction of the dynamics of new SARS-CoV-2 infections during the current COVID-19 pandemic is critical for public health planning of efficient health care allocation and monitoring the effects of policy interventions. We describe a new approach that forecasts the number of incident cases in the near future given past occurrences using only a small number of assumptions.MethodsOur approach to forecasting future COVID-19 cases involves 1) modeling the observed incidence cases using a Poisson distribution for the daily incidence number, and a gamma distribution for the series interval; 2) estimating the effective reproduction number assuming its value stays constant during a short time interval; and 3) drawing future incidence cases from their posterior distributions, assuming that the current transmission rate will stay the same, or change by a certain degree.ResultsWe apply our method to predicting the number of new COVID-19 cases in a single state in the U.S. and for a subset of counties within the state to demonstrate the utility of this method at varying scales of prediction. Our method produces reasonably accurate results when the effective reproduction number is distributed similarly in the future as in the past. Large deviations from the predicted results can imply that a change in policy or some other factors have occurred that have dramatically altered the disease transmission over time.ConclusionWe presented a modelling approach that we believe can be easily adopted by others, and immediately useful for local or state planning.
A methodology to generate longitudinally updated ACLF prognostication scores from electronic health record data
Authors: Ge Jin , Najafi Nader , Zhao Wendi , Somsouk Ma , Fang Margaret , Lai Jennifer C. 
Published: November 2020

AbstractBackground and AimsQueries of electronic health record (EHR) data repositories allow for automated data collection. These techniques have not been utilized in hepatology due to previous inability to capture hepatic encephalopathy (HE) grades, which are inputs for acute-on-chronic liver failure (ACLF) models. Here, we describe a methodology to utilizing EHR data to calculate rolling ACLF scores.MethodsWe examined 239 patient-admissions with end-stage liver disease 7/2014-6/2019. We mapped EHR flowsheet data to determine HE grades and calculated two longitudinally updated ACLF scores. We validated HE grades and ACLF diagnoses via chart review; and calculated sensitivity, specificity, and Cohen’s kappa.ResultsOf 239 patient-admissions analyzed, 37% women, 46% non-Hispanic White, median age 60 years, median MELD-Na at admission. Of the 239, 7% were diagnosed with NACSELD-ACLF at admission, 27% during the hospitalization, and 9% at discharge. Forty percent diagnosed with CLIF-C-ACLF at admission, 51% during the hospitalization, and 34% at discharge.From chart review of 51 admissions, we found sensitivities and specificities for any HE (grades 1-4) were 92-97% and 76-95%, respectively; for severe HE (grades 3-4) were 100% and 78-98%, respectively. Cohen’s kappa between flowsheet and chart review HE grades ranged 0.55-0.72. Sensitivities and specificities for NACSELD-ACLF diagnoses were 75-100% and 96-100%, respectively; for CLIF-C-ACLF diagnoses were 91-100% and 96-100%, respectively. We generated approximately 28 unique ACLF scores per patient per admission-day.ConclusionIn this study, we developed an informatics-based methodology for to calculate longitudinally updated ACLF scores. This opens new analytic potentials, such big data methods to develop electronic phenotypes for ACLF patients.
Effect of hot zone infection outbreaks on the dynamics of SARS-CoV-2 spread in the community at large
Authors: Wodarz Dominik , Komarova Natalia L. , Schang Luis M. 
Published: November 2020

AbstractTransmission of SARS-CoV-2 appears especially effective in “hot zone” locations where individuals interact in close proximity. We present mathematical models describing two types of hot zones. First, we consider a metapopulation model of infection spread where transmission hot zones are explicitly described by independent demes in which the same people repeatedly interact (referred to as “static” hot zones, e.g. nursing homes, food processing plants, prisons, etc.). These are assumed to exists in addition to a “community at large” compartment in which virus transmission is less effective. This model yields a number of predictions that are relevant to interpreting epidemiological patterns in COVID19 data. Even if the rate of community virus spread is assumed to be relatively slow, outbreaks in hot zones can temporarily accelerate initial community virus growth, which can lead to an overestimation of the viral reproduction number in the general population. Further, the model suggests that hot zones are a reservoir enabling the prolonged persistence of the virus at “infection plateaus” following implementation of non-pharmaceutical interventions, which has been frequently observed in data. The second model considers “dynamic” hot zones, which can repeatedly form by drawing random individuals from the community, and subsequently dissolve (e.g. restaurants, bars, movie theaters). While dynamic hot zones can accelerate the average rate of community virus spread and can provide opportunities for targeted interventions, they do not predict the occurrence of infection plateaus or other atypical epidemiological dynamics. The models therefore identify two types of transmission hot zones with very different effects on the infection dynamics, which warrants further epidemiological investigations.
Risk of Polymyxin B-induced Acute Kidney Injury in Non-adjusted Dose Versus Adjusted Dose based on Renal Function: a retrospective cohort study
Authors: Zheng Guanhao , Zhou Shenghui , Du Ning , Cai Jiaqi , Bai Hao , He Juan , Bian Xiaolan 
Published: November 2020

AbstractBackgroundThis study aimed to observe the difference in risk of polymyxin B-induced acute kidney injury with or without dose adjustment by patients’ renal function.MethodA retrospective cohort analysis was carried out for patients who were treated with polymyxin B in Ruijin Hospital Affiliated to Shanghai Jiaotong University School of Medicine from November 2018 to October 2019. Patients were divided into adjusted dosage group and non-adjusted dosage group depended on dosage adjustment with renal function or not. A comparison of acute kidney injury incidence between the two groups was the primary outcome of this research. The secondary outcome included hospital length of stay, microbiological cure, clinical cure, and 30-day mortality.ResultA total of 115 patients met the requirements of this study and were included in the analysis. Thirty-five patients were included in the non-adjusted dosage group and 80 in the adjusted dosage group. Patients from both groups had similar characteristics. The total daily dose of polymyxin B in the Non-adjusted dosage group was significantly higher than the adjusted dosage group (1.98 mg/kg/d vs 1.59 mg/kg/d, P=0.001). For the primary outcome of this research, no significant difference in the incidence of acute kidney injury was observed in these two groups (47.5% vs 37.14%, P=0.304), as well as the secondary outcomes, including hospital length of stay, microbiological cure, clinical cure, 30-day mortality.ConclusionDosing adjustment renally could not lower the risk of polymyxin B-induced acute kidney injury significantly. A non-adjusted dosing strategy of polymyxin B is recommended when patients suffered from various levels of renal impairment.
A Nasal Spray Solution of Grapefruit Seed Extract plus Xylitol Displays Virucidal Activity Against SARS-Cov-2In Vitro
Authors: Ferrer Gustavo , Betancourt Arian , Go Camille Celeste , Vazquez Hector , Westover Jonna B. , Cagno Valeria , Tapparel Caroline , Sanchez-Gonzalez Marcos A. 
Published: November 2020

ABSTARCTThe severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), responsible for the ongoing pandemic coronavirus disease 2019 (COVID-19) has triggered worldwide concerted efforts in an attempt to identify effective therapies. In the present study, we have identified two candidate agents with potential activity against SARS-CoV-2 which can be administered intranasally, namely, xylitol and grape seed fruit extract (GSE). A commercially available nasal spray (Xlear) combining xylitol and GSE has been available for years, but the antiviral effects of this solution have not been documented. Thisin vitrostudy examined the virucidal effect of Xlear against SARS-CoV-2. To this end, two independent sets of experiments were carried out to test the hypothesis that Xlear is an effective (Experiment I) and replicable (Experiment II) means to deactivate SARS-CoV-2. When tested against SARS-CoV-2, the test compound GSE 0.2% was the only compound effective at reducing >3 log10 CCID50 infectious virus from, 3.67 log10 CCID50/0.1 mL to an undetectable amount of infectious virus. The present results validated by two independent sets of experiments, performed by different labs, on different viral strains, provide early evidence to encourage further pilot and clinical studies aimed at investigating the use of Xlear as a potential treatment for COVID-19
Visuomotor Activation of Inhibition-Processing in Pediatric Obsessive Compulsive Disorder: A Magnetoencephalography Study
Authors: Nishat Eman , Dockstader Colleen , Wheeler Anne L. , Tan Thomas , Anderson John A. E. , Mendlowitz Sandra , Mabbott Donald J. , Arnold Paul D. , Ameis Stephanie H. 
Published: November 2020

AbstractBackgroundThe ability to inhibit a response is a component of executive control that is impaired in many individuals with obsessive compulsive disorder (OCD) and may contribute to clinical symptoms. This study explored whether neural processing during response inhibition, measured using magnetoencephalography (MEG), differed in a sample of medication-naïve youth with OCD, compared to typically developing controls (TDC).MethodsData was acquired from 20 medication-naïve children and youth with OCD (11.9 ± 2.1 SD years) and 14 TDC (12.3 ± 2.1 SD years). MEG was used to localize and characterize neural activity during a Go/No-Go task. Regional differences in amplitude of activity during a Go and No-Go condition between OCD versus TDC were examined.ResultsIn response to the visual cue presented during the Go condition, participants with OCD showed significantly increased amplitude of activity in the primary motor (MI) cortex compared to TDC. A trend towards decreased amplitude of activity in the orbitofrontal cortex in OCD versus TDC was also found during stop errors in the No-Go condition.ConclusionOur preliminary study in a small medication-naïve sample suggests that neural response within motor and orbitofrontal regions may be altered during Go/No-Go Task performance, and that MEG as an imaging tool may be sensitive to detecting such differences.
Airway tissue stem cells reutilize the embryonic proliferation regulator, Tgfß-Id2 axis, for tissue regeneration
Authors: Kiyokawa Hirofumi , Yamaoka Akira , Matsuoka Chisa , Tokuhara Tomoko , Abe Takaya , Morimoto Mitsuru 
Published: November 2020

SummaryDuring development, quiescent basal stem cells are derived from proliferative primordial progenitors through the cell cycle slowdown. In contrast, quiescent basal cells contribute to tissue repair during adult tissue regeneration by shifting from slow-cycling to proliferating and subsequently back to slow-cycling. Although sustained basal cell proliferation results in tumorigenesis, the molecular mechanisms regulating these transitions remain unknown. Using temporal single-cell transcriptomics of developing murine airway progenitors andin vivogenetic validation experiments, we found that Tgfß signaling slowed down cell cycle by inhibitingId2expression in airway progenitors and contributed to the specification of slow-cycling basal cell population during development. In adult tissue regeneration, reduced Tgfß signaling restoredId2expression and initiated epithelial regeneration.Id2overexpression andTgfbr2knockout enhanced epithelial proliferation; however, persistentId2expression in basal cells drove hyperplasia at a rate that resembled a precancerous state. Together, the Tgfß-Id2 axis commonly regulates the proliferation transitions in airway basal cells during development and regeneration, and its fine-tuning is critical for normal regeneration while avoiding basal cell hyperplasia.
Hybrid Living Capsules Autonomously Produced by Engineered Bacteria
Authors: Birnbaum Daniel P. , Manjula-Basavanna Avinash , Kan Anton , Joshi Neel S. 
Published: November 2020

AbstractBacterial cellulose (BC) has excellent material properties and can be produced cheaply and sustainably through simple bacterial culture, but BC-producing bacteria lack the extensive genetic toolkits of model organisms such asEscherichia coli. Here, we describe a simple approach for producing highly programmable BC materials through incorporation of engineeredE. coli. The acetic acid bacteriumGluconacetobacter hanseniiwas co-cultured with engineeredE. coliin droplets of glucose-rich media to produce robust cellulose capsules, which were then colonized by theE. coliupon transfer to selective lysogeny broth media. We show that the encapsulatedE. colican produce engineered protein nanofibers within the cellulose matrix, yielding hybrid capsules capable of sequestering specific biomolecules from the environment and enzymatic catalysis. Furthermore, we produced capsules capable of altering their own bulk physical properties through enzyme-induced biomineralization. This novel system, based on autonomous biological fabrication, significantly expands the functionality of BC-based living materials.
BEEM-Static: Accurate inference of ecological interactions from cross-sectional metagenomic data
Authors: Li Chenhao , Av-Shalom Tamar V. , Gerald Tan Jun Wei , Samantha Kwah Junmei , Chng Kern Rei , Nagarajan Niranjan 
Published: November 2020

AbstractMotivationThe structure and function of diverse microbial communities is underpinned by ecological interactions that remain uncharacterized. With rapid adoption of metagenomic sequencing for studying microbiomes, data-driven inference of microbial interactions based on abundance correlations is widely used, but with the drawback that ecological interpretations may not be possible. Leveraging cross-sectional metagenomic datasets for unravelling ecological structure in a scalable manner thus remains an open problem.MethodsWe present an expectation-maximization algorithm (BEEM-Static) that can be applied to cross-sectional datasets to infer interaction networks based on an ecological model (generalized Lotka-Volterra). The method exhibits robustness to violations in model assumptions by using statistical filters to identify and remove corresponding samples.ResultsBenchmarking against 10 state-of-the-art correlation based methods showed that BEEM-Static can infer presence and directionality of ecological interactions even with relative abundance data (AUC-ROC>0.85), a task that other methods struggle with (AUC-ROC<0.63). In addition, BEEM-Static can tolerate a high fraction of samples (up to 40%) being not at steady state or coming from an alternate model. Applying BEEM-Static to a large public dataset of human gut microbiomes (n=4,617) identified multiple stable equilibria that better reflect ecological enterotypes with distinct carrying capacities and interactions for key species.ConclusionBEEM-Static provides new opportunities for mining ecologically interpretable interactions and systems insights from the growing corpus of metagenomic data.
The SC-SNc pathway boosts appetitive locomotion in predatory hunting
Authors: Huang Meizhu , Li Dapeng , Pei Qing , Xie Zhiyong , Gu Huating , Liu Aixue , Chen Zijun , Wang Yi , Sun Fangmiao , Li Yulong , Zhang Jiayi , He Miao , Xie Yuan , Zhang Fan , Qi Xiangbing , Shang Congping , Cao Peng 
Published: November 2020

ABSTRACTAppetitive locomotion is essential for organisms to approach rewards, such as food and prey. How the brain controls appetitive locomotion is poorly understood. In a naturalistic goal-directed behavior—predatory hunting, we demonstrate an excitatory brain circuit from the superior colliculus (SC) to the substantia nigra pars compacta (SNc) to boost appetitive locomotion. The SC-SNc pathway transmitted locomotion-speed signals to dopamine neurons and triggered dopamine release in the dorsal striatum. Activation of this pathway increased the speed and frequency of approach during predatory hunting, an effect that depended on the activities of SNc dopamine neurons. Conversely, synaptic inactivation of this pathway impaired appetitive locomotion but not defensive or exploratory locomotion. Together, these data revealed the SC as an important source to provide locomotion-related signals to SNc dopamine neurons to boost appetitive locomotion.