bluuebunny/crossref_metadata_2025_split huggingface dataset:
Evidence of integrated health service delivery during COVID-19 in low- and middle-income countries: protocol for a scoping review
Authors: Neill Rachel , Hasan Md Zabir , Das Priyanka , Venugopal Vasuki , Jain Nishant , Arora Dinesh , Gupta Shivam 
Published: July 2020

AbstractIntroductionThe importance of integrated, people-centered health systems has been recognized as a central component of achieving Universal Health Coverage. Integration has also been highlighted as a critical element for building resilient health systems that can stand the shock of health emergencies. However, there is dearth of research and systematic synthesis of evidence on the synergistic relationship between integrated health services and pandemic preparedness in low- and low-middle income countries (LMICs). Thus, the authors are organizing a scoping review aiming to explore application of integrated health service delivery approaches during the emerging COVID-19 pandemic in LMICs.Methods and analysisThis scoping review adheres to the six steps for scoping reviews from Arksey and O’Malley (2005). Peer reviewed scientific literature will be systematically assembled utilizing a standardized and replicable search strategy from seven electronic databases, including PubMed, Embase, Scopus, Web of Science, CINAHL Plus, the World Health Organization’s Global Research Database on COVID-19, and LitCovid. Initially, the title and abstract of the collected literature, published in English from December 2019 to June 2020, will be screened for inclusion which will be followed by a full text review by two independent reviewers. Data will be charted using a data extraction form and reported in narrative format with accompanying data matrixes.Ethics and disseminationNo ethical approval is required for the review. The study will be conducted from June to December 2020. Results from this study will provide a snapshot of the evidence currently being generated related to integrated health service delivery in response to the COVID-19 pandemic. The findings will be developed into reports and a peer-reviewed articles and will assist policy makers in making pragmatic and evidence-based decisions for current and future pandemic response.Article SummaryStrengths and limitations of this studyThe scoping review aims to uncover new evidence in response to the evolving pandemic and will not assess the quality of existing evidenceThe review will map a rapidly emerging evidence base in response to COVID-19 from seven different electronic databases that can be used to inform response and recovery strategies in LMICsThe early research and published evidence on the COVID-19 pandemic was focused in high-income and upper-middle income countries, thus, we expect evidence of from LMICs may be scarceThe scoping review is limited to peer review publications that were originally written in English or have translated versions
Clinical Impact, Costs, and Cost-Effectiveness of Expanded SARS-CoV-2 Testing in Massachusetts
Authors: Neilan Anne M. , Losina Elena , Bangs Audrey C. , Flanagan Clare , Panella Christopher , Eskibozkurt G. Ege , Mohareb Amir , Hyle Emily P. , Scott Justine A. , Weinstein Milton C. , Siedner Mark J. , Reddy Krishna P. , Harling Guy , Freedberg Kenneth A. , Shebl Fatma M. , Kazemian Pooyan , Ciaranello Andrea L. 
Published: July 2020

ABSTRACTBackgroundWe projected the clinical and economic impact of alternative testing strategies on COVID-19 incidence and mortality in Massachusetts using a microsimulation model.MethodsWe compared five testing strategies: 1) PCR-severe-only: PCR testing only patients with severe/critical symptoms; 2) Self-screen: PCR-severe-only plus self-assessment of COVID-19-consistent symptoms with self-isolation if positive; 3) PCR-any-symptom: PCR for any COVID-19-consistent symptoms with self-isolation if positive; 4) PCR-all: PCR-any-symptom and one-time PCR for the entire population; and, 5) PCR-all-repeat: PCR-all with monthly re-testing. We examined effective reproduction numbers (Re, 0.9-2.0) at which policy conclusions would change. We used published data on disease progression and mortality, transmission, PCR sensitivity/specificity (70/100%) and costs. Model-projected outcomes included infections, deaths, tests performed, hospital-days, and costs over 180-days, as well as incremental cost-effectiveness ratios (ICERs, $/quality-adjusted life-year [QALY]).ResultsIn all scenarios, PCR-all-repeat would lead to the best clinical outcomes and PCR-severe-only would lead to the worst; at Re 0.9, PCR-all-repeat vs. PCR-severe-only resulted in a 63% reduction in infections and a 44% reduction in deaths, but required >65-fold more tests/day with 4-fold higher costs. PCR-all-repeat had an ICER <$100,000/QALY only when Re ≥1.8. At all Re values, PCR-any-symptom was cost-saving compared to other strategies.ConclusionsTesting people with any COVID-19-consistent symptoms would be cost-saving compared to restricting testing to only those with symptoms severe enough to warrant hospital care. Expanding PCR testing to asymptomatic people would decrease infections, deaths, and hospitalizations. Universal screening would be cost-effective when paired with monthly retesting in settings where the COVID-19 pandemic is surging.
Factors associated with psychological distress in health-care workers during an infectious disease outbreak: A rapid living systematic review
Authors: Sirois Fuschia M. , Owens Janine 
Published: July 2020

AbstractBackgroundHealth-care workers (HCW) are at risk for psychological distress during an infectious disease outbreak due to the demands of dealing with a public health emergency.AimsTo examine the factors associated with psychological distress among HCW during an outbreak.MethodWe systematically reviewed literature on the factors associated with psychological distress (demographic characteristics, occupational, social, psychological, and infection-related factors) in HCW during an outbreak (COVID-19, SARS, MERS, H1N1, H7N9, Ebola). Four electronic databases were searched (2000 to 10 July 2020) for relevant peer-reviewed research according to a pre-registered protocol. A narrative synthesis was conducted to identify fixed, modifiable, and infection-related factors.ResultsFrom the 3335 records identified, 52 with data from 54,800 HCW were included. All but two studies were cross-sectional. Consistent evidence indicated that being female, a nurse, experiencing stigma, maladaptive coping, having contact or risk for contact with infected patients, and being quarantined, were risk factors for psychological distress among HCW. Personal and organisational social support, perceiving control, positive work attitudes, sufficient information about the outbreak and proper protection, training and resources, were associated with less psychological distress.ConclusionsHCW who may be most at risk for psychological distress during an outbreak require early intervention and ongoing monitoring as there is some evidence that HCW distress can persist for years after an outbreak. Further research is needed to track the associations of risk factors with distress over time and the extent to which certain factors are inter-related and linked to sustained or transient distress.
Assessing the Age Specificity of Infection Fatality Rates for COVID-19: Systematic Review, Meta-Analysis, and Public Policy Implications
Authors: Levin Andrew T. , Hanage William P. , Owusu-Boaitey Nana , Cochran Kensington B. , Walsh Seamus P. , Meyerowitz-Katz Gideon 
Published: July 2020

Structured AbstractObjectiveDetermine age-specific infection fatality rates for COVID-19 to inform public health policies and communications that help protect vulnerable age groups.MethodsStudies of COVID-19 prevalence were collected by conducting an online search of published articles, preprints, and government reports. A total of 111 studies were reviewed in depth and screened. Studies of 33 locations satisfied the inclusion criteria and were included in the meta-analysis. Age-specific IFRs were computed using the prevalence data in conjunction with reported fatalities four weeks after the midpoint date of the study, reflecting typical lags in fatalities and reporting. Meta-regression procedures in Stata were used to analyze IFR by age.ResultsOur analysis finds a exponential relationship between age and IFR for COVID-19. The estimated age-specific IFRs are very low for children and younger adults but increase progressively to 0.4% at age 55, 1.3% at age 65, 4.2% at age 75, and 14% at age 85. We find that differences in the age structure of the population and the age-specific prevalence of COVID-19 explain nearly 90% of the geographical variation in population IFR.DiscussionThese results indicate that COVID-19 is hazardous not only for the elderly but also for middle-aged adults, for whom the infection fatality rate is two orders of magnitude greater than the annualized risk of a fatal automobile accident and far more dangerous than seasonal influenza. Moreover, the overall IFR for COVID-19 should not be viewed as a fixed parameter but as intrinsically linked to the age-specific pattern of infections. Consequently, public health measures to mitigate infections in older adults could substantially decrease total deaths.
A systematic review of utilisation of diurnal timing information in clinical trial design for Long QT syndrome
Authors: Seed Lydia M , Hearn Timothy J 
Published: July 2020

AbstractDiurnal oscillations in human cardiac electrophysiology are thought to be under the control of the endogenous circadian clock. The incidence of arrhythmic events in patients with Long QT syndrome (LQTS) varies diurnally. The diurnal variation in QT interval has previously been identified as a potential for error in clinical trials which utilise ECG measurement. We performed a systematic review of clinical trials for LQTS to identify practice around specification of timing information for point electrocardiogram (ECG) measurements, analysis of continual ECG recordings ≥24 hours, and drug delivery. Despite guidelines having been issued around the analysis of 24-hour ECG recordings, we identify a lack of usage of detailed time of day information in trial design for LQTS studies, which has the potential to affect the interpretation of the results of drug trials. We identify that, in contrast, clinical trials for QT prolonging drugs demonstrate increased incorporation of time of day information of both QT analysis and drug dosing. We provide a visual portal to allow trial designers and clinicians to better understand timing of common cardiac-targeting drugs, and to bear this concept in mind in the design of future clinical trials.
Time to SARS-CoV-2 Clearance Among Patients with Cancer and COVID-19
Authors: Xu Wenxin , Piper-Vallillo Andrew J. , Bindal Poorva , Wischhusen Jonathan , Patel Jaymin M. , Costa Daniel B , Peters Mary Linton B. 
Published: July 2020

Key PointsQuestionWhat is the median time to clearance of SARS-CoV-2 among cancer patients according to currently used criteria?FindingsIn this single-institution retrospective cohort study, the median time to SARS-CoV-2 clearance was 50 days using the ASCO/CDC criteria of 2 negative RT-PCR assays >24 hours apart. Using alternative criteria of 1 negative RT-PCR assay (UK-NICE) or CDC clinical criteria (10 days after first positive RT-PCR and 3 days after last symptoms), median clearance times were 31 days and 13 days, respectively.MeaningSARS-CoV-2 clearance times differ substantially depending on criteria used and may be prolonged in cancer patients.
A novel haplotype-based eQTL approach identifies genetic associations not detected through conventional SNP-based methods
Authors: Bkhetan Ziad Al , Chana Gursharan , Ong Cheng Soon , Goudey Benjamin , Ramamohanarao Kotagiri 
Published: July 2020

AbstractMotivationThe high accuracy of current haplotype phasing tools has enabled the interrogation of haplotype (or phase) information more widely in genetic investigations. Including such information in eQTL analysis complements SNP-based approaches as it has the potential to detect associations that may otherwise be missed.ResultsWe have developed a haplotype-based eQTL approach calledeQTLHapto investigate associations between gene expression and haplotype blocks. Using simulations, we demonstrate that eQTLHap significantly outperforms typical SNP-based eQTL methods when the causal genetic architecture involves multiple SNPs. We show that phasing errors slightly impact the sensitivity of the proposed method (< 4%). Finally, the application of eQTLHap to real GEUVADIS and GTEx datasets finds 22 associations that replicated in larger studies or other tissues and could not be detected using a single-SNP approach.Availabilityhttps://github.com/ziadbkh/eQTLHap.
Freshly Thawed Cryobanked Human Neural Stem Cells Engraft within Endogenous Neurogenic Niches and Restore Cognitive Function Following Chronic Traumatic Brain Injury
Authors: Badner Anna , Reinhardt Emily K. , Nguyen Theodore V. , Midani Nicole , Marshall Andrew T. , Lepe Cherie , Echeverria Karla , Lepe Javier , Torrecampo Vincent , Bertan Sara H. , Tran Serinee H. , Anderson Aileen J. , Cummings Brian J. 
Published: July 2020

AbstractHuman neural stem cells (hNSCs) have potential as a cell therapy following traumatic brain injury (TBI). While various studies have demonstrated the efficacy of NSCs from on-going culture, there is a significant gap in our understanding of freshly thawed cells from cryobanked stocks – a more clinically-relevant source. To address these shortfalls, the therapeutic potential of our previously validated Shef-6.0 human embryonic stem cell (hESC)-derived hNSC line was tested following long-term cryostorage and thawing prior to transplant. Immunodeficient athymic nude rats received a moderate unilateral controlled cortical impact (CCI) injury. At 4-weeks post-injury, 6×105freshly thawed hNSCs were transplanted into six injection sites (2 ipsi- and 4 contra-lateral) with 53.4% of cells surviving three months post-transplant. Interestingly, most hNSCs were engrafted in the meninges and the lining of lateral ventricles, associated with high CXCR4 expression and a chemotactic response to SDF1alpha (CXCL12). While some expressed markers of neuron, astrocyte, and oligodendrocyte lineages, the majority remained progenitors, identified through doublecortin expression (78.1%). Importantly, transplantation resulted in improved spatial learning and memory in Morris water maze navigation and reduced risk-taking behavior in an elevated plus maze. Investigating potential mechanisms of action, we identified an increase in ipsilateral host hippocampus cornu ammonis (CA) neuron survival, contralateral dentate gyrus (DG) volume and DG neural progenitor morphology as well as a reduction in neuroinflammation. Together, these findings validate the potential of hNSCs to restore function after TBI and demonstrate that long-term bio-banking of cells and thawing aliquots prior to use may be suitable for clinical deployment.Significance StatementThere is no cure for chronic traumatic brain injury (TBI). While human neural stem cells (hNSCs) offer a potential treatment, no one has demonstrated efficacy of thawed hNSCs from long-term cryobanked stocks. Frozen aliquots are critical for multisite clinical trials, as this omission impacted the use of MSCs for graft versus host disease. This is the first study to demonstrate the efficacy of thawed hNSCs, while also providing support for novel mechanisms of action – linking meningeal and ventricular engraftment to reduced neuroinflammation and improved hippocampal neurogenesis. Importantly, these changes also led to clinically relevant effects on spatial learning/memory and risk-taking behavior. Together, this new understanding of hNSCs lays a foundation for future work and improved opportunities for patient care.
SambaR: an R package for fast, easy and reproducible population-genetic analyses of biallelic SNP datasets
Authors: de Jong Menno J. , de Jong Joost F. , Hoelzel A. Rus , Janke Axel 
Published: July 2020

ABSTRACTBackgroundSNP datasets can be used to infer a wealth of information about natural populations, including information about their structure, genetic diversity, and the presence of loci under selection. However, SNP data analysis can be a time-consuming and challenging process, not in the least because at present many different software packages are needed to execute and depict the wide variety of mainstream population-genetic analyses. Here we present SambaR, an integrative and user-friendly R package which automates and simplifies quality control and population-genetic analyses of biallelic SNP datasets. SambaR allows users to perform mainstream population-genetic analyses and to generate a wide variety of ready to publish graphs with a minimum number of commands (less than ten). These wrapper commands call functions of existing packages (including adegenet, ape, LEA, poppr, pcadapt and StAMPP) as well as new tools uniquely implemented in SambaR.ResultsWe tested SambaR on online available SNP datasets and found that SambaR can process datasets of millions of SNPs and hundreds of individuals within hours, given sufficient computing power. Newly developed tools implemented in SambaR facilitate optimization of filter settings, objective interpretation of ordination analyses, enhance comparability of diversity estimates from reduced representation library SNP datasets, and generate reduced SNP panels and structure-like plots with Bayesian population assignment probabilities.ConclusionSambaR facilitates rapid population genetic analyses on biallelic SNP datasets by removing three major time sinks: file handling, software learning, and data plotting. In addition, SambaR provides a convenient platform for SNP data storage and management, as well as several new utilities, including guidance in setting appropriate data filters.Availability and implementationThe SambaR source script, manual and example datasets are distributed through GitHub:https://github.com/mennodejong1986/SambaR
Transmission efficiency drives host-microbe associations
Authors: Leftwich Philip T. , Edgington Matthew P. , Chapman Tracey 
Published: July 2020

AbstractSequencing technologies have fueled a rapid rise in descriptions of microbial communities associated with hosts, but what is often harder to ascertain is their evolutionary significance. Here we review the existing literature on the role of vertical (VT), horizontal (HT), environmental acquisition, and mixed modes (MMT) of transmission for establishing animal host-microbe associations. We then modelled four properties of gut microbiota proposed as key to promoting animal host-microbe relationships: modes of transmission, host reproductive mode, host mate choice, and host fitness. We found: (i) MMT led to the highest frequencies of host-microbe associations, and some environmental acquisition or HT of microbes was required for persistent associations to form unless VT was perfect; (ii) host reproductive mode (sexual vs asexual) and host mate choice (for microbe carriers vs non-carriers) had little impact on the establishment of host-microbe associations; (iii) host mate choice did not itself lead to reproductive isolation, but could reinforce it; (iv) changes in host fitness due to host-microbe associations had a minimal impact upon the formation of co-associations. When we introduced a second population, into which host-microbe carriers could disperse but in which environmental acquisition did not occur, highly efficient VT was required for host-microbe co-associations to persist. Our study reveals that transmission mode is of key importance in establishing host-microbe associations.
A reference tissue atlas for the human kidney
Authors: Hansen Jens , Sealfon Rachel , Menon Rajasree , Eadon Michael T. , Lake Blue B. , Steck Becky , Dobi Dejan , Parikh Samir , Sigdel Tara K. , Zhang Guanshi , Velickovic Dusan , Barwinska Daria , Alexandrov Theodore , Rashmi Priyanka , Otto Edgar A. , Rose Michael P. , Anderton Christopher R. , Shapiro John P. , Pamreddy Annapurna , Winfree Seth , He Yongqun , de Boer Ian H. , Hodgin Jeffrey B. , Barisoni Laura , Naik Abhijit S. , Sharma Kumar , Sarwal Minnie M. , Zhang Kun , Himmelfarb Jonathan , Rovin Brad , El-Achkar Tarek M. , Laszik Zoltan , He John Cijiang , Dagher Pierre C. , Valerius M. Todd , Jain Sanjay , Satlin Lisa , Troyanskaya Olga G. , Kretzler Matthias , Iyengar Ravi , Azeloglu Evren U. ,   for the Kidney Precision Medicine Project
Published: July 2020

AbstractKidney Precision Medicine Project (KPMP) is building a spatially-specified human tissue atlas at the single-cell resolution with molecular details of the kidney in health and disease. Here, we describe the construction of an integrated reference tissue map of cells, pathways and genes using unaffected regions of nephrectomy tissues and undiseased human biopsies from 55 subjects. We use single-cell and -nucleus transcriptomics, subsegmental laser microdissection bulk transcriptomics and proteomics, near-single-cell proteomics, 3-D nondestructive and CODEX imaging, and spatial metabolomics data to hierarchically identify genes, pathways and cells. Integrated data from these different technologies coherently describe cell types/subtypes within different nephron segments and interstitium. These spatial profiles identify cell-level functional organization of the kidney tissue as indicative of their physiological functions and map different cell subtypes to genes, proteins, metabolites and pathways. Comparison of transcellular sodium reabsorption along the nephron to levels of mRNAs encoding the different sodium transporter genes indicate that mRNA levels are largely congruent with physiological activity.This reference atlas provides an initial framework for molecular classification of kidney disease when multiple molecular mechanisms underlie convergent clinical phenotypes.
Robust partitioning of microRNA targets from downstream regulatory changes
Authors: Patel Ravi K. , West Jessica D. , Jiang Ya , Fogarty Elizabeth A. , Grimson Andrew 
Published: July 2020

ABSTRACTThe biological impact of microRNAs (miRNAs) is determined by their targets, and robustly identifying direct miRNA targets remains challenging. Existing methods suffer from high falsepositive rates and are unable to effectively differentiate direct miRNA targets from downstream regulatory changes. Here, we present an experimental and computational framework to deconvolute post-transcriptional and transcriptional changes using a combination of RNA-seq and PRO-seq. This novel approach allows us to systematically profile the regulatory impact of a miRNA. We refer to this approach as CARP:CombinedAnalysis ofRNA-seq andPRO-seq. We apply CARP to multiple miRNAs and show that it robustly distinguishes direct targets from downstream changes, while greatly reducing false positives. We validate our approach using Argonaute eCLIP-seq and ribosome profiling, demonstrating that CARP defines a comprehensive repertoire of targets. Using this approach, we identify miRNA-specific activity of target sites within the open reading frame. Additionally, we show that CARP facilitates the dissection of complex changes in gene regulatory networks triggered by miRNAs and identification of transcription factors that mediate downstream regulatory changes. Given the robustness of the approach, CARP would be particularly suitable for dissecting miRNA regulatory networksin vivo.