bluuebunny/crossref_metadata_2025_split huggingface dataset:
Acceptability of Routine Point-of-Care Early Infant Diagnosis in Eight African Countries: Findings From a Qualitative Assessment of Clinical and Laboratory Personnel
Authors: Bianchi Flavia , Clemens Sara , Arif Zainab , Sacks Emma , Cohn Jennifer ,   on behalf of the EGPAF POC EID Study Team
Published: June 2020

Background:
The Elizabeth Glaser Pediatric AIDS Foundation introduced point-of-care (POC) testing for early infant diagnosis (EID) of HIV in 8 African countries. Understanding experiences and opinions of users can help facilitate introduction and sustainability.

Setting:
Cameroon, Côte d'Ivoire, Eswatini, Kenya, Lesotho, Mozambique, Rwanda, and Zimbabwe.

Methods:
Structured interviews with health care workers (HCWs) providing EID services and semistructured interviews with national and regional laboratory managers or EID program managers were conducted before and after the implementation of POC EID. Survey responses were analyzed and compared; open-ended responses were analyzed by theme.

Results:
In total, 234 and 175 interviews with HCWs and 28 and 14 interviews with laboratory or program managers were conducted before and after the introduction of POC EID, respectively. In preintervention interviews, challenges identified with laboratory-based EID testing included distance from patients' residence to the health facility, time-consuming sample transportation to central laboratories, stockout of testing kits, and long wait times for results. Postintervention data revealed that HCWs found POC EID easy to use and were very satisfied with the fast turnaround time and ability to initiate treatment for HIV-infected infants sooner. Laboratory managers were also supportive of scaling-up POC testing although cautious of the need for reliable infrastructure to operate platforms. The recommendation was that POC EID be integrated within the national diagnostic testing network.

Conclusions:
Support for POC EID from key stakeholders is essential for sustainability. Overall, participants supported the rollout of POC testing for EID, noting challenges and opportunities for scaling-up POC EID and recommending integration into the overall EID system.
Impact of Routine Point-of-Care Versus Laboratory Testing for Early Infant Diagnosis of HIV: Results From a Multicountry Stepped-Wedge Cluster-Randomized Controlled Trial
Authors: Sacks Emma , Cohn Jennifer , Ochuka Bernard , Mafaune Haurovi , Chadambuka Addmore , Odhiambo Collins , Masaba Rose , Githuka George , Mahomva Agnes , Mushavi Angela , Lemaire Jean-Francois , Bianchi Flavia , Machekano Rhoderick 
Published: June 2020

Background:
Although the World Health Organization recommends HIV-exposed infants receive a 6-week diagnostic test, few receive results by 12 weeks. Point-of-care (POC) early infant diagnosis (EID) may improve timely diagnosis and treatment. This study assesses the impact of routine POC versus laboratory-based EID on return of results by 12 weeks of age.

Methods:
This was a cluster-randomized stepped-wedge trial in Kenya and Zimbabwe. In each country, 18 health facilities were randomly selected for inclusion and randomized to timing of POC implementation.

Findings:
Nine thousand five hundred thirty-nine infants received tests: 5115 laboratory-based and 4424 POC. In Kenya and Zimbabwe, respectively, caregivers were 1.29 times [95% confidence interval (CI): 1.27 to 1.30, P < 0.001] and 4.56 times (95% CI: 4.50 to 4.60, P < 0.001) more likely to receive EID results by 12 weeks of age with POC versus laboratory-based EID. POC significantly reduced the time between sample collection and return of results to caregiver by an average of 23.03 days (95% CI: 4.85 to 21.21, P < 0.001) in Kenya and 62.37 days (95% CI: 58.94 to 65.80, P < 0.001) in Zimbabwe. For HIV-infected infants, POC significantly increased the percentage initiated on treatment, from 43.2% to 79.6% in Zimbabwe, and resulted in a nonsignificant increase in Kenya from 91.7% to 100%. The introduction of POC EID also significantly reduced the time to antiretroviral therapy initiation by an average of 17.01 days (95% CI: 9.38 to 24.64, P < 0.001) in Kenya and 56.00 days (95% CI: 25.13 to 153.76, P < 0.001) in Zimbabwe.

Conclusions:
POC confers significant advantage on the proportion of caregivers receiving timely EID results, and improves time to results receipt and treatment initiation for infected infants. Where laboratory-based EID systems are unable to deliver results to caregivers rapidly, POC should be implemented as part of an integrated testing system.
Brief Report: HIV Incidence Among Older Adults in a Rural South African Setting: 2010–2015
Authors: Gómez-Olivé F. Xavier , Houle Brian , Rosenberg Molly , Kabudula Chodziwadziwa , Mojola Sanyu , Rohr Julia K. , Clark Samuel , Angotti Nicole , Schatz Enid , Kahn Kathleen , Bärnighausen Till , Menken Jane 
Published: June 2020

Introduction:
In South Africa, evidence shows high HIV prevalence in older populations, with sexual behavior consistent with high HIV acquisition and transmission risk. However, there is a dearth of evidence on older people's HIV incidence.

Methods:
We used a 2010–2011 cohort of HIV-negative adults in rural South Africa who were 40 years or older at retest in 2015–2016 to estimate HIV incidence over a 5-year period. We used Poisson regression to measure the association of HIV seroconversion with demographic and behavioral covariates. We used inverse probability sampling weights to adjust for nonresponse in 2015, based on a logistic regression with predictors of sex and age group at August 2010.

Results:
HIV prevalence increased from 21% at baseline to 23% in the follow-up survey. From a cohort of 1360 individuals, 33 seroconverted from HIV negative at baseline, giving an overall HIV incidence rate of 0.39 per 100 person-years [95% confidence interval (CI): 0.28 to 0.57]. The rate for women was 0.44 (95% CI: 0.30 to 0.67), double than that for men, 0.21 (95% CI: 0.10 to 0.51). Incidence rate ratios (IRRs) again show women's risk of seroconverting double than that of men (IRR = 2.04, P value = 0.098). In past age 60, the IRR of seroconversion was significantly lower than that for those in their 40s (60–69, IRR = 0.09, P value = 0.002; 70–79, IRR = 0.14, P value = 0.010).

Conclusions:
The risk of acquiring HIV is not zero for people older than 50 years, especially women. Our findings highlight the importance of acknowledging that older people are at high risk of HIV infection and that HIV prevention and treatment campaigns must take them into consideration.
Phagocytosis–Inflammation Crosstalk in Sepsis: New Avenues for Therapeutic Intervention
Authors: Hortová-Kohoutková Marcela , Tidu Federico , De Zuani Marco , Šrámek Vladimír , Helán Martin , Frič Jan 
Published: June 2020

ABSTRACT
Phagocytosis is a complex process by which cells within most organ systems remove pathogens and cell debris. Phagocytosis is usually followed by inflammatory pathway activation, which promotes pathogen elimination and inhibits pathogen growth. Delayed pathogen elimination is the first step in sepsis development and a key factor in sepsis resolution. Phagocytosis thus has an important role during sepsis and likely contributes to all of its clinical stages. However, only a few studies have specifically explored and characterized phagocytic activity during sepsis. Here, we describe the phagocytic processes that occur as part of the immune response preceding sepsis onset and identify the elements of phagocytosis that might constitute a predictive marker of sepsis outcomes. First, we detail the key features of phagocytosis, including the main receptors and signaling hallmarks associated with different phagocytic processes. We then discuss how the initial events of phagosome formation and cytoskeletal remodeling might be associated with known sepsis features, such as a cytokine-driven hyperinflammatory response and immunosuppression. Finally, we highlight the unresolved mechanisms of sepsis development and progression and the need for cross-disciplinary approaches to link the clinical complexity of the disease with basic cellular and molecular mechanisms.
DECONbench: a benchmarking platform dedicated to deconvolution methods for tumor heterogeneity quantification
Authors: Decamps Clémentine , Arnaud Alexis , Petitprez Florent , Ayadi Mira , Baurès Aurélia , Armenoult Lucile ,   HADACA consortium, Nicolle Rémy , Tomasini Richard , de Reyniès Aurélien , Cros Jérôme , Blum Yuna , Richard Magali 
Published: June 2020

AbstractMotivationQuantification of tumor heterogeneity is essential to better understand cancer progressionand to adapt therapeutic treatments to patient specificities.ResultsWe present DECONbench, a web-based application to benchmark computational methods dedicated to quantify of cell-type heterogeneity in cancer. DECONbench includes benchmark datasets, computational methods and performance evaluation. It allows submission of new methods.Availability and implementationDECONbench is hosted on the open source codalab competition platform. It is freely available at:https://competitions.codalab.org/competitions/23660.Supplementary informationAdditional information is available online and on our website:https://cancer-heterogeneity.github.io/deconbench.html.
A molecular phylogeny of forktail damselflies (genusIschnura) reveals a dynamic macroevolutionary history of female colour polymorphisms
Authors: Blow Rachel , Willink Beatriz , Svensson Erik I. 
Published: June 2020

AbstractColour polymorphisms are popular study systems among biologists interested in evolutionary dynamics, genomics, sexual selection and sexual conflict. In many damselfly groups, such as in the globally distributed genusIschnura(forktails), sex-limited female colour polymorphisms occur in multiple species. Female-polymorphic species contain two or three female morphs, one of which phenotypically matches the male (androchrome or male mimic) and the other(s) which are phenotypically distinct from the male (heterochrome). These female colour polymorphisms are thought to be maintained by frequency-dependent sexual conflict, but their macroevolutionary histories are unknown, due to the lack of a robust molecular phylogeny. Here, we present the first time-calibrated phylogeny ofIschnura, using a multispecies coalescent approach (StarBEAST2) and incorporating both molecular and fossil data for 41 extant species (55% of the genus). We estimate the age ofIschnurato be between 13.8 and 23.4 millions of years, i.e. Miocene. We infer the ancestral state of this genus as female monomorphism with heterochrome females, with multiple gains and losses of female polymorphisms, evidence of trans-species female polymorphisms and a significant positive relationship between female polymorphism incidence and current geographic range size. Our study provides a robust phylogenetic framework for future research on the dynamic macroevolutionary history of this clade with its extraordinary diversity of sex-limited female polymorphisms.
Striatal dopamine synthesis capacity reflects smartphone social activity
Authors: Westbrook Andrew , Ghosh Arko , van den Bosch Ruben , Cools Roshan 
Published: June 2020

AbstractStriatal dopamine has been implicated in social behavior across humans, rodents, and non-human primates in artificial laboratory settings with highly-practiced tasks and fixed reward contingencies. Whether striatal dopamine drives naturalistic, spontaneous social behavior remains unclear. Here, we leverage day-to-day logs of unconstrained smartphone behavior and establish a novel link between smartphone social activity and individual differences in striatal dopamine synthesis capacity using [18F]-DOPA PET in (N=22) healthy adult humans. We find a strong relationship such that a higher proportion of social app interactions correlates with lower dopamine synthesis capacity in the bi-lateral putamen. Permutation tests and penalized regressions provide evidence that this link between dopamine synthesis capacity and social versus non-social smartphone taps is specific. These observations provide a key empirical grounding for current speculations about dopamine’s role in digital social behavior.
Syntax-sensitive regions of Broca’s area and the posterior temporal lobe are differentially recruited by production and perception
Authors: Matchin William , Wood Emily 
Published: June 2020

AbstractNeuroimaging studies of syntactic processing typically result in similar activation profiles in Broca’s area and the posterior temporal lobe (PTL). However, substantial functional dissociations between these regions have been demonstrated with respect to lesion-symptom mapping in aphasia. To account for this, Matchin & Hickok (2020) proposed that both regions play a role in syntactic processing, broadly construed, but attribute distinct functions to these regions with respect to production and comprehension. Here we report an fMRI study designed to test this hypothesis by contrasting the subvocal articulation and comprehension of structured jabberwocky phrases (syntactic), sequences of real words (lexical), and sequences of pseudowords (phonological). We defined two sets of language-selective regions of interest (ROIs) in individual subjects for Broca’s area and the PTL using the contrasts [syntactic > lexical] and [syntactic > phonological]. We found robust significant interactions of comprehension and production between these two regions at the syntactic level, for both sets of language-selective ROIs. This suggests a core difference in the function of these regions: language-selective subregions of Broca’s area play a role in syntax driven by the demands of production, whereas language-selective subregions of the PTL play a role in syntax driven by the demands of comprehension.
SARS-CoV-2 Whole Genome Amplification and Sequencing for Effective Population-Based Surveillance and Control of Viral Transmission
Authors: Harilal Divinlal , Ramaswamy Sathishkumar , Loney Tom , Suwaidi Hanan Al , Khansaheb Hamda , Alkhaja Abdulmajeed , Varghese Rupa , Deesi Zulfa , Nowotny Norbert , Alsheikh-Ali Alawi , Tayoun Ahmad Abou 
Published: June 2020

AbstractBackgroundWith the gradual reopening of economies and resumption of social life, robust surveillance mechanisms should be implemented to control the ongoing COVID-19 pandemic. Unlike RT-qPCR, SARS-CoV-2WholeGenomeSequencing (cWGS) has the added advantage of identifying cryptic origins of the virus, and the extent of community-based transmissions versus new viral introductions, which can in turn influence public health policy decisions. However, practical and cost considerations of cWGS should be addressed before it can be widely implemented.MethodsWe performed shotgun transcriptome sequencing using RNA extracted from nasopharyngeal swabs of patients with COVID-19, and compared it to targeted SARS-CoV-2 full genome amplification and sequencing with respect to virus detection, scalability, and cost-effectiveness. To track virus origin, we used open-source multiple sequence alignment and phylogenetic tools to compare the assembled SARS-CoV-2 genomes to publicly available sequences.ResultsWe show a significant improvement in whole genome sequencing data quality and viral detection using amplicon-based target enrichment of SARS-CoV-2. With enrichment, more than 99% of the sequencing reads mapped to the viral genome compared to an average of 0.63% without enrichment. Consequently, a dramatic increase in genome coverage was obtained using significantly less sequencing data, enabling higher scalability and significant cost reductions. We also demonstrate how SARS-CoV-2 genome sequences can be used to determine their possible origin through phylogenetic analysis including other viral strains.ConclusionsSARS-CoV-2 whole genome sequencing is a practical, cost-effective, and powerful approach for population-based surveillance and control of viral transmission in the next phase of the COVID-19 pandemic.
Effect of tocilizumab in hospitalized patients with severe pneumonia COVID-19: a cohort study
Authors: Rossi Benjamin , Nguyen Lee S. , Zimmermann Philippe , Boucenna Faiza , Dubret Louis , Baucher Louise , Guillot Helene , Bouldouyre Marie-Anne , Allenbach Yves , Salem Joe-Elie , Barsoum Paul , Oufella Arezki , Gros Helene 
Published: June 2020

AbstractBackgroundTocilizumab, a drug targeting interleukin-6 administrated in the right timeframe may be beneficial in coronavirus-disease-2019 (COVID-19). We aimed to assess its benefit, drawing from observations in compassionately treated patients.MethodsIn a retrospective case-control study, treatment effect (tocilizumab 400mg, single-dose) was assessed using three statistical methods: propensity-score matching, Cox multivariable survival and inverse probability score weighting (IPSW) analyses. Were included all patients hospitalized with COVID-19, who presented severity criteria with SpO2≤96% despite O2-support ≥6L/min for more than 6 hours. Were excluded patients in critical care medicine department and those under invasive mechanical ventilation. Primary outcome was a composite of mortality and ventilation, with a maximum follow-up of 28 days.Results246 patients were included (106 treated by tocilizumab). They were 67.6 ±15.3 years-old, with 95 (38.5%) women. Delay between first symptoms and inclusion was 8.4 ±4.5 days. Overall, 105 (42.7%) patients presented the primary outcome, with 71 (28.9%) deaths during the 28-days follow-up. Propensity-score-matched 84 pairs of comparable patients. In the matched cohort (n = 168), tocilizumab was associated with fewer primary outcomes (hazard ratio (HR) = 0.49 (95% confidence interval (95CI) = 0.3–0.81), p-value = 0.005). These results were similar in the overall cohort (n = 246), with Cox multivariable analysis yielding a protective association between tocilizumab and primary outcome (adjusted HR = 0.26 (95CI = 0.135–0.51, p = 0.0001), confirmed by IPSW analysis (p<0.0001). Analyses on mortality with 28-days follow-up yielded similar results.ConclusionIn this retrospective study, tocilizumab single-dose was associated with improved survival without mechanical ventilation in patients with severe COVID-19.
Multiple, independent, common variants overlapping known and putative gut enhancers at RET, SEMA3 and NRG1 underlie Hirschsprung disease risk in European ancestry subjects
Authors: Kapoor Ashish , Nandakumar Priyanka , Auer Dallas R. , Sosa Maria X. , Ross Holly , Bollinger Juli , Yan Jia , Berrios Courtney ,   The Hirschsprung Disease Research Collaborative (HDRC), Chakravarti Aravinda 
Published: June 2020

AbstractPurposeHirschsprung disease (HSCR) is a developmental disorder of the enteric nervous system (ENS) characterized by congenital aganglionosis, and where individual cases harbor coding risk variants in ENS genes. Low-penetrance, common, noncoding variants at RET, SEMA3 and NRG1 loci have been associated in HSCR as well, implicating variable gene expression mediated by cis-regulatory element (CRE) variants as the causal mechanism. However, the extent and combinatorial effects of all putative CRE variants within and across these loci on HSCR is unknown.MethodsUsing 583 HSCR subjects, one of the largest samples of European ancestry studied, and genotyping 56 tag variants we evaluated association of all common variants overlapping putative gut CREs and fine-mapped variants at RET, SEMA3 and NRG1.ResultsWe demonstrate that 28 and 8 tag variants, several of which are independent, overlapping putative-enhancers at the RET and SEMA3 loci, respectively, and, 2 fine-mapped tag variants at NRG1 locus, are associated with HSCR. We demonstrate that risk increases with increasing risk allele dosage from multiple variants within and across these loci and varies >25- fold.ConclusionGene regulatory networks in HSCR-relevant cell types quantify the total burden of risk alleles through sensing reduced gene expression of multiple genes on disease.
Nucleus translocation of tRNA synthetase mediates late integrated stress response
Authors: Wei Na , Cui Haissi , Shi Yi , Fu Guangsen , Rauniyar Navin , Yates John R. , Yang Xiang-Lei 
Published: June 2020

AbstractVarious stress conditions are signaled through phosphorylation of translation initiation factor eIF2α to inhibit global translation while selectively activating transcription factor ATF4 to aid cell survival and recovery. However, this integrated stress response is acute and cannot resolve lasting stress. Here we report that TyrRS, a member of the aminoacyl-tRNA synthetase family capable of responding to diverse stress factors through cytosol-nucleus translocation and activating stress-response genes, also inhibits global translation, however at a later stage than eIF2α/ATF4 and mTOR responses. Excluding TyrRS from the nucleus over-activates protein synthesis and increases apoptosis in cells under prolonged oxidative stress. Nuclear TyrRS transcriptionally represses translation genes by recruiting TRIM28 and/or NuRD complex. We propose TyrRS, possibly along with other family members, can sense a variety of stress signals through intrinsic properties of this enzyme and its strategically located nuclear localization signal and integrate them by nucleus-translocation to effect protective responses against prolonged stress.
NCOA3identified as a new candidate to explain autosomal dominant progressive hearing loss
Authors: da Silva Rodrigo Salazar , Dantas Vitor Lima Goes , Alves Leandro Ucela , Batissoco Ana Carla , Oiticica Jeanne , Lawrence Elizabeth A , Kawafi Abdelwahab , Yang Yushi , Nicastro Fernanda Stávale , Novaes Beatriz Caiuby , Hammond Chrissy , Kague Erika , Netto Regina Célia Mingroni 
Published: June 2020

AbstractHearing loss is a frequent sensory impairment in humans and genetic factors account for an elevated fraction of the cases. We have investigated a large family of five generations, with 15 reported individuals presenting non-syndromic, sensorineural, bilateral and progressive hearing loss, segregating as an autosomal dominant condition. Linkage analysis, using SNP-array and selected microsatellites, identified a region of 13cM in chromosome 20 as the best candidate to harbour the causative mutation. After exome sequencing and filtering of variants, only one predicted deleterious variant in theNCOA3gene (NM_181659, c.2810C>G; p.Ser937Cys) fit in with our linkage data. RT-PCR, immunostaining andin situhybridization showed expression ofncoa3in the inner ear of mice and zebrafish. We generated a stable homozygous zebrafish mutant line using the CRISPR/Cas9 system.ncoa3−/−did not display any major morphological abnormalities in the ear, however, anterior macular hair cells showed altered orientation. Surprisingly, chondrocytes forming the ear cartilage showed abnormal behaviour inncoa3−/−, detaching from their location, invading the ear canal and blocking the cristae. Adult mutants displayed accumulation of denser material wrapping the otoliths ofncoa3−/−and increased bone mineral density. Altered zebrafish swimming behaviour corroborates a potential role ofncoa3in hearing loss. In conclusion, we identified a potential candidate gene to explain hereditary hearing loss, and our functional analyses suggest subtle and abnormal skeletal behaviour as mechanisms involved in the pathogenesis of progressive sensory function impairment.