bluuebunny/crossref_metadata_2025_split huggingface dataset:
ABCDE and ABCDEF care bundles
Authors: Moraes Fabio da Silva , Marengo Lívia Luize , Moura Mariana Del Grossi , Bergamaschi Cristiane de Cássia , de Sá Del Fiol Fernando , Lopes Luciane Cruz , Silva Marcus Tolentino , Barberato-Filho Silvio 
Published: June 2022

Abstract

Background:
The ABCDE (Awakening and Breathing Coordination of daily sedation and ventilator removal trials, Delirium monitoring and management, and Early mobility and exercise) and ABCDEF (Assessment, prevent and manage pain, Both spontaneous awakening and spontaneous breathing trials, Choice of analgesia and sedation, assess, prevent and manage Delirium, Early mobility and exercise, Family engagement) care bundles consist of small sets of evidence-based interventions and are part of the science behind Intensive Care Unit (ICU) liberation. This review sought to analyse the process of implementation of ABCDE and ABCDEF care bundles in ICUs, identifying barriers, facilitators and changes in perception and attitudes of healthcare professionals; and to estimate care bundle effectiveness and safety.

Methods:
We selected qualitative and quantitative studies addressing the implementation of ABCDE and ABCDEF bundles in the ICU, identified on MEDLINE, Embase, CINAHL, The Cochrane Library, Web of Science, Epistemonikos, PsycINFO, Virtual Health Library and Open Grey, without restriction on language or date of publication, up to June 2018. The outcomes measured were ICU and hospital length of stay; mechanical ventilation time; incidence and prevalence of delirium or coma; level of agitation and sedation; early mobilization; mortality in ICU and hospital; change in perception, attitude or behaviour of the stakeholders; and change in knowledge of health professionals. Two reviewers independently selected the studies, performed data extraction, and assessed risk of bias and methodological quality. A meta-analysis of random effects was performed.

Results:
Twenty studies were included, 13 of which had a predominantly qualitative and 7 a quantitative design (31,604 participants). The implementation strategies were categorized according to the taxonomy developed by the Cochrane Effective Practice and Organization of Care Group and eighty strategies were identified. The meta-analysis results showed that implementation of the bundles may reduce length of ICU stay, mechanical ventilation time, delirium, ICU and hospital mortality, and promoted early mobilization in critically-ill patients.

Conclusions
: This study can contribute to the planning and execution of the implementation process of ABCDE and ABCDEF care bundles in ICUs. However, the effectiveness and safety of these bundles need to be corroborated by further studies with greater methodological rigor.

Protocol registration:
PROSPERO CRD42019121307.
A review on the evolution of simulation-based training to help build a safer future
Authors: Bienstock Jared , Heuer Albert 
Published: June 2022

Abstract
Throughout history, simulation has been used to demonstrate various techniques, acquire skills, and maintain best practices in healthcare. Simulation has evolved significantly, primarily because of the extent to which it can enhance both clinical proficiency and patient care. Although simulation-based training (SBT) in healthcare has grown exponentially in the 21st century, it has been around for centuries. This paper aims to reflect on the history and evolution of simulation in healthcare and review its current applications in order to provide a foundation for developing new applications for future expanded use.
Challenges associated with diagnostic exome sequencing in liver diseases
Authors: Kong Xiao-Fei , Bogyo Kelsie , Kapoor Sheena , Groopman Emily E. , Thomas-Wilson Amanda , Cocchi Enrico , Rasouly Hila Milo , Zheng Beishi , Sun Siming , Zhang Junying , Martinez Mercedes , Vittorio Jennifer M , Dove Lorna M. , Marasa Maddalena , Wang Timothy C. , Verna Elizabeth C. , Worman Howard J. , Gharavi Ali G. , Goldstein David B. , Wattacheril Julia 
Published: June 2022

AbstractExome sequencing (ES) has been used in a variety of clinical settings but there are limited data on its utility for diagnosis and/or prediction of monogenic liver diseases. We analyzed ES data in 758 patients with liver diseases., We developed a curated list of 502 genes for monogenic disorders associated with liver phenotypes and analyzed ES data for these genes in 758 patients with chronic liver diseases (CLD). For comparison, we examined ES data in 7,856 self-declared healthy controls (HC), and 2,187 patients with chronic kidney disease (CKD). Candidate pathogenic (P) or likely pathogenic (LP) variants were initially identified in 19.9% of participants, most of which were attributable to previously reported pathogenic variants with implausibly high allele frequencies. After variant annotation and stringent filtering based on population minor allele frequency, we detected a significant enrichment of P/LP variants in the CLD cohort compared to the HC cohort (X2test OR: 5.00, 95% CI:3.06-8.18,, p-value=4.5 e-12). A second-level manual annotation was necessary to capture true pathogenic variants that were removed by stringent allele frequency filters. After these sequential steps, the diagnostic rate of monogenic disorders was 5.7% in the CLD cohort, attributable to P/LP variants in 25 genes. We also identified concordant liver disease phenotypes for 15/22 kidney disease patients with P/LP variants in liver genes, mostly associated with cystic liver disease phenotypes. Clinically confirmed sequencing results had many implications for clinical management, including familial testing for early diagnosis and management, preventative screening for associated comorbidities, and in some cases for therapy. Exome sequencing provided a 5.7% diagnostic rate in CLD patients and required multiple rounds of review to reduce both false positive and false negative findings. The identification of concordant phenotypes in many patients with P/LP variants and no known liver disease also indicates a potential for predictive testing for selected monogenic liver disorders.
Over the hills and far away: linking landscape factors with cavity excavation on living forest trees by the Black Woodpecker (Dryocopus martius, L. 1758)
Authors: Cabrera Cedric , Monnet Jean-Matthieu , Boutteaux Jean-Jacques , Doutau Baptiste , Denis Pascal , Paillet Yoan 
Published: June 2022

AbstractThe Black Woodpecker (Dryocopus martius, L. 1758) is the largest primary cavity excavator in Western Europe. Its cavities represent an essential microhabitat for many other forest species and the landscape factors linked with cavity excavation by the Black Woodpecker are needed to support the conservation of this species. Such relationships should thus be quantified at the scale of the home range in Western Europe.We used cavity maps by foresters and naturalists to build a large (2689 cavity bearing trees) database distributed over 11 sites in France. Based on this and on a set of background points, we analysed the effects of stand composition and landscape features (forest cover, landscape connectivity and fragmentation) at three different scales around each plot corresponding to a forest management unit (10ha), the core (100ha) and extended (250ha) home range scales.We showed that landscape shape index and forest composition (especially the presence of mixed forests) had significant effects but that the magnitude varied across the three scales. We notably observed the strongest effects at the core home range scale (100ha), indicating that Black Woodpecker requirements for cavity excavation are more pronounced at this scale. The Black Woodpecker tend to avoid conifer-dominated stands to excavate cavities, but benefits from mixed forests, that couple favourable foraging and cavity excavation sites. The bird also prefers continuous forest landscapes with low edge densities. We also showed that effects of landscape were stronger in wetter climates and higher slopes, indicating context-dependence.Forest planning rarely integrates the landscape patterns in western temperate Europe, a better understanding of the features linked with cavity excavation by the Black Woodpecker may hence help to better integrate their conservation in forest management planning. Our results also show the importance to maintain mixed broadleaf-conifer forests as well as continuous and well-connected forest landscapes to favour features that benefit secondary cavity nesters at the large scale.
Binge alcohol drinking alters the differential control of cholinergic interneurons over nucleus accumbens D1 and D2 medium spiny neurons
Authors: Kolpakova Jenya , van der Vinne Vincent , Gimenez-Gomez Pablo , Le Timmy , Martin Gilles E. 
Published: June 2022

AbstractBackgroundVentral striatal cholinergic interneurons (ChIs) play a central role in basal ganglia function by regulating associative learning and reward processing. In the nucleus accumbens (NAc), ChIs regulate glutamatergic, dopaminergic, and GABAergic neurotransmission. However, it is unclear how ChIs orchestrate the control of these neurotransmitters to determine the excitability of medium spiny neurons (MSNs) expressing either dopamine D1 or D2 receptors. Additionally, the effects of binge alcohol drinking on ChIs-mediated modulation of glutamatergic synaptic transmission in NAc MSNs are also undefined.MethodsWe optogenetically stimulated ChIs while recording evoked and spontaneous excitatory postsynaptic currents (sEPSCs) in D1- and D2-MSN of ChAT.ChR2.eYFPxDrd1.tdtomato mice. To determine the effect of ChIs on mouse behavior and alcohol consumption, we implanted ChAT.ChR2.eYFP mice with fiber optic cannulas and stimulated ChIs while mice were allowed to drink 20% alcohol using the binge alcohol drinking- in-the-dark (DID) paradigm.ResultsWe demonstrated that NAc ChIs decrease the frequency of spontaneous excitatory postsynaptic currents (sEPSCs) in both D1- and D2-MSNs,. While inhibition of D1-MSNs glutamate release by ChIs depends on dopamine release, that of D2-MSNs results from a direct interactions between ChIs and glutamatergic terminals. Interestingly, after two weeks of binge alcohol drinking, the effect of ChIs stimulation on glutamate release was reversed in D1-MSNs, while its effect on D2-MSNs remained unchanged. Finally, in vivo optogenetic stimulation of NAc ChIs significantly increased alcohol consumption.ConclusionsThese results identify ChIs as a key target for the regulation of NAc circuitry and as a potential treatment of alcohol addiction.
T-cell potential for CD19-expressing malignancies revealed by multi-dimensional single-cell profiling
Authors: Rezvan Ali , Romain Gabrielle , Fathi Mohsen , Heeke Darren , Martinez-Paniagua Melisa , An Xingyue , Bandey Irfan N , Saeedi Arash , Sadeghi Fatemeh , Fousek Kristen , Puebla-Osorio Nahum , Cooper Laurence J.N. , Bernatchez Chantale , Singh Harjeet , Ahmed Nabil , Mattie Mike , Bot Adrian , Neelapu Sattva , Varadarajan Navin 
Published: June 2022

ABSTRACTAdoptive immunotherapy with T cells expressing chimeric antigen receptors (CARs) for B-cell malignancies serves as a model for identifying subsets with superior clinical activity. We profiled the infusion products (IP) of 16 patients with large B-cell lymphoma (LBCL) using an integrated suite of single-cell assays to reveal the therapeutic potential of CD19-specific CAR+ T cells. Timelapse imaging microscopy in nanowell grids (TIMING) profiling revealed that T cells from responders showed migration (persistent motion for at least one body length), and migration was associated with serial killing capacity. In addition, confocal microscopy revealed that migration is linearly correlated with both mitochondrial volume and lysosomal volume; and scRNA-seq demonstrated that T cells from responders were enriched in pathways related to T-cell killing, migration and actin cytoskeleton, and TCR clustering. A marker-free sorting strategy enriched T cells with migratory capacity and validated serial killing, bioenergetics, and in vivo efficacy. In aggregate, we demonstrate that migration is a cell-intrinsic biomarker independent of CAR design or biomanufacturing, desired in the bioactivity of CAR+ T cells associated with clinical antitumor efficacy.
CNVscore calculates pathogenicity scores for copy number variants together with uncertainty estimates accounting for learning biases in reference Mendelian disorder datasets
Authors: Requena Francisco , Salgado David , Malan Valérie , Sanlaville Damien , Bilan Frédéric , Béroud Christophe , Rausell Antonio 
Published: June 2022

AbstractCopy number variants (CNVs) are a major cause of rare pediatric diseases with a broad spectrum of phenotypes. Genetic diagnosis based on comparative genomic hybridization tests typically identifies ∼8-10% of patients as having CNVs of unknown significance, revealing the current limits of clinical interpretation. The adoption of whole-genome sequencing (WGS) as a first-line genetic test has significantly increased the load of CNVs identified in single genomes. Alongside short- and long-read sequencing technologies, a number of pathogenicity scores have been developed for filtering and prioritizing large sets of candidate CNVs in clinical settings. However, current approaches are often based, either explicitly or implicitly, on clinically annotated reference sets, which are likely to bias their predictions. In this study we developed CNVscore, a supervised-learning approach combining tree ensembles and a Bayesian classifier trained on pathogenic and non-pathogenic CNVs from reference databases. Unlike previous approaches, CNVscore couples pathogenicity estimates with uncertainty scores, making it possible to evaluate the suitability of a model for the query CNVs. Comprehensive comparative benchmark tests across independent sets and against alternative methods showed that CNVscore effectively distinguishes between pathogenic and benign CNVs. We also found that CNVs associated with CNVscores of low uncertainty were predicted with significantly higher accuracy than those of high uncertainty. However, the performance of current scoring approaches, including CNVscore, was compromised on CNV sets enriched in highly uncertain variants and presenting unconventional features, such as functionally relevant non-coding elements or the presence of disease genes irrelevant for the clinical phenotypes investigated. Finally, we used the CNVscore framework to guide CNV scoring model selection for the French National Database of Constitutional CNVs (BANCCO), which includes clinical diagnosis annotations. The CNVscore framework provides an objective strategy for leveraging the uncertainty on bioinformatic predictions to enhance the assessment of CNV pathogenicity in rare-disease cohorts. CNVscore is available as open-source software from https://github.com/RausellLab/CNVscore and is integrated into the CNVxplorer webserver http://cnvxplorer.com.
Protection against Omicron BA.2 reinfection conferred by primary Omicron or pre-Omicron infection with and without mRNA vaccination
Authors: Carazo Sara , Skowronski Danuta M. , Brisson Marc , Barkati Sapha , Sauvageau Chantal , Brousseau Nicholas , Gilca Rodica , Fafard Judith , Talbot Denis , Ouakki Manale , Gilca Vladimir , Carignan Alex , Deceuninck Geneviève , De Wals Philippe , De Serres Gaston 
Published: June 2022

AbstractBackgroundWe estimated the protection against the Omicron BA.2 variant associated with prior primary infection (PI) due to pre-Omicron or Omicron BA.1 virus, with and without mRNA vaccination.MethodsA test-negative case-control study was conducted among healthcare workers (HCWs) tested for SARS-CoV-2 in Quebec, Canada, between March 27 and June 4, 2022, when BA.2 predominated and was presumptively diagnosed. Logistic regression models compared the likelihood of BA.2 reinfection (second positive test ≥30 days after PI) among HCWs with history of PI and none to three doses of mRNA vaccine versus infection-naïve, unvaccinated HCWs.FindingsAmong 37,732 presumed BA.2 cases, 2,521 (6.7%) and 659 (1.7%) were reinfections following pre-Omicron or BA.1 PI, respectively. Among 73,507 controls, 7,360 (10.0%) and 12,315 (16.8%) had a pre-Omicron or BA.1 PI, respectively. Pre-Omicron PI was associated with 38% (95%CI:19-53) reduction in BA.2 infection risk, with higher BA.2 protection among those also vaccinated with one (56%), two (69%) or three (70%) vaccine doses. Omicron BA.1 PI was associated with greater protection against BA.2 (72%; 95%CI:65-78), higher among two-dose vaccinated at 96% (95%CI:95-96) but not improved with a third dose (96%; 95%CI:95-97). Hybrid Omicron BA.1 PI plus two or three dose vaccine-induced protection persisted for five months post-infection.InterpretationTwice-vaccinated individuals who experienced BA.1 infection were subsequently well-protected for a prolonged period against BA.2 reinfection and derived no meaningful added benefit against BA.2 from a third dose of mRNA vaccine.
HIV and SARS-CoV-2 infection in postpartum Kenyan women and their infants
Authors: Begnel Emily R. , Chohan Bhavna H. , Ojee Ednah , Adhiambo Judith , Owiti Prestone , Ogweno Vincent , Holland LaRinda A. , Fish Carolyn S. , Richardson Barbra A. , Khan Adam K. , Maqsood Rabia , Lim Efrem S. , Lehman Dara A. , Slyker Jennifer , Kinuthia John , Wamalwa Dalton , Gantt Soren 
Published: June 2022

ABSTRACTBackgroundHIV may increase SARS-CoV-2 infection risk and COVID-19 severity generally, but data are limited about its impact on postpartum women and their infants. As such, we characterized SARS-CoV-2 infection among mother-infant pairs in Nairobi, Kenya.MethodsWe conducted a nested study of 53 HIV-uninfected and 51 healthy women living with HIV, as well as their HIV-exposed uninfected (N=41) and HIV-unexposed (N=48) infants, participating in a prospective cohort. SARS-CoV-2 serology was performed on plasma collected between 1 May-31 December 2020 to determine the incidence, risk factors, and symptoms of infection. SARS-CoV-2 RNA PCR and sequencing was also performed on stool samples from seropositive participants.ResultsSARS-CoV-2 seropositivity was found in 38% of the 104 mothers and in 17% of the 89 infants. There was no significant association between SARS-CoV-2 infection and maternal HIV (Hazard Ratio [HR]=1.51, 95% CI: 0.780-2.94) or infant HIV exposure (HR=1.48, 95% CI: 0.537-4.09). Maternal SARS-CoV-2 was associated with a >10-fold increased risk of infant infection (HR=10.3, 95% CI: 2.89-36.8). Twenty percent of participants had symptoms, but no participant experienced severe COVID-19 or death. Seroreversion occurred in ∼30% of mothers and infants. SARS-CoV-2 sequences obtained from stool were related to contemporaneously circulating variants.ConclusionsThese data indicate that postpartum Kenyan women and their infants were at high risk for SARS-CoV-2 infection in 2020, and that antibody responses waned rapidly. However, most cases were asymptomatic and healthy women living with HIV did not have a substantially increased risk of infection or severe COVID-19.
Mechanoregulatory role of TRPV4 in prenatal skeletal development
Authors: Khatib Nidal , Monsen James , Ahmed Saima , Huang Yuming , Hoey David A. , Nowlan Niamh C. 
Published: June 2022

AbstractBiophysical cues are essential for guiding skeletal development, but the mechanisms underlying the physical regulation of cartilage and bone formation are unknown. TRPV4 is a cell membrane ion channel responsible for transducing mechanical stimuli as a means of regulating skeletal cell homeostatic processes. Dysregulation of TRPV4 is associated with several skeletal developmental pathologies, indicating its involvement in cartilage and bone development, potentially in a mechanosensing capacity. In this study, we test the hypothesis that mechanically mediated prenatal skeletogenesis depends on TRPV4 activity. We first validate a novel model where we establish that dynamically loading embryonic mouse hindlimb explants cultured ex vivo promotes joint cartilage growth and morphogenesis, but not diaphyseal mineralization. We next reveal that TRPV4 protein expression is mechanically regulated and spatially localized to patterns of high biophysical stimuli in the femoral condyles of cultured limbs. Finally, we demonstrate that TRPV4 activity is crucial for the mechanical regulation of joint cartilage growth and shape, mediated via the control of cell proliferation and matrix biosynthesis, indicating a mechanism by which mechanical loading could direct morphogenesis during joint formation. We conclude that the regulatory pathways initiated by TRPV4 mechanotransduction are essential for the for the cartilage response to physical stimuli during skeletal development. Therefore, TRPV4 may be a valuable target for the development of therapeutic skeletal disease modifying drugs and developmentally-inspired tissue engineering strategies for skeletal repair.
Genetic landscape of Human neutrophil antigen variants in India from population-scale genomes
Authors: Rophina Mercy , Bhoyar Rahul C , Imran Mohamed , Senthivel Vigneshwar , Divakar Mohit Kumar , Mishra Anushree , Jolly Bani , Sivasubbu Sridhar , Scaria Vinod 
Published: June 2022

AbstractBackgroundAntibodies against human neutrophil antigens (HNAs) play a significant role in various clinical conditions such as neonatal alloimmune neutropenia (NAIN). Transfusion-related acute lung injury (TRALI) and other non-hemolytic transfusion reactions. This study aims to identify the genotype and allele frequencies of HNAs in the healthy Indian population.MethodsGenetic variants from whole genomes of 1029 healthy Indian individuals were retrieved to accurately perform frequency estimation of HNA-1, HNA-3, HNA-4 and HNA-5 alleles using in-house computational pipeline.ResultsIn HNA class I, the genotype frequencies of FCGR3B*01 (HNA1a/a), FCGR3B*02 (HNA1b/b) and FCGR3B*03 (HNA1c/c) were 0.29%, 27.31% and 1.75% respectively. In HNA-3 the frequencies of HNA3a/a (SLC44A2*01), HNA3a/b and HNA3b/b (SLC44A2*02) were found to be 62.0%, 31.7% and 5.8% respectively. Frequency of ITGAM*01 encoding HNA4a/a was 90.1% and that of ITGAM*02 encoding HNA4b/b was 0.3%. Furthermore, HNA5a/a (ITGAL*01) and HNA5b/b (ITGAL*02) were found to have 12.9% and 48.6% genotype frequencies in the Indian population respectively. It was also found that the allele frequency HNA-5 variant, rs2230433 (ITGAL_chr16:30506720G>C) encoding 5b allele was highly prevalent (78.2%) in the Indian population which was comparable to South Asians (65.6%) but differed greatly from East Asians (14.3%), Latino Americans (25.7%), African-Americans (42.2%), European-Finnish (25.4%), European-non-Finnish (29.4%), Greater Middle Easterners (34.5%), Amish (30.2%) and Ashkenazi Jewish (31.4%).ConclusionThis study presents the first comprehensive report of HNA variant and genotype frequencies using large scale representative whole genome sequencing data of the Indian population. Significant difference was observed in the prevalence of HNA5a and HNA5b in India in comparison to other global populations.