bluuebunny/crossref_metadata_2025_split huggingface dataset:
“It's Like Your Whole Body Hates You”
Authors: Gray Emily , Wilson Marian , Landis Tullamora T. , Little-Gott Angela 
Published: May 2023

Abstract
A qualitative descriptive study was conducted concurrent with a larger study investigating the effects of hyperbaric oxygen treatment on withdrawal symptoms for adults receiving daily methadone for opioid use disorder. The aims of this study were to (a) evaluate the perceptions of withdrawal symptoms and sleep characteristics of study participants and (b) explore the experiences of participation in the parent trial of hyperbaric oxygen treatment.
Adults with opioid use disorder can experience distressing symptoms related to withdrawal as well as co-occurring symptoms; sleep impairment is frequently reported. Few studies have examined how adults who receive medication for opioid use disorder experience sleep. A preliminary study of adults receiving daily methadone found that withdrawal symptoms were improved after hyperbaric oxygen treatment. This study explores the narrative of opioid users who report their overall experiences with withdrawal and sleep as well as their experiences of hyperbaric therapy.
A convenience sample of six participants was recruited, who represented a small subgroup of participants who completed the larger hyperbaric treatment study. Data were collected via semistructured interviews. Data were analyzed using the qualitative content analysis guidelines proposed by Schreier (2012). All participants described poor overall sleep hygiene and disturbed sleep. More than half of the respondents reported improved or eliminated withdrawal symptoms, and all reported improvement in sleep quality after participation in the sleep study.
This companion study confirms that subjective sleep disturbance may be prevalent for adults with opioid use disorder. Participants felt the experience of hyperbaric oxygen treatment produced a positive effect on sleep.
Simple design and analysis strategies for solving problems in observational orthopaedic clinical research
Authors: Brown Kelsey E. , Flores Michael J. , Slobogean Gerard , Shearer David , Gitajn Ida Leah , Morshed Saam 
Published: May 2023

Summary:
Randomized controlled trials are the gold standard to establishing causal relationships in clinical research. However, these studies are expensive and time consuming to conduct. This article aims to provide orthopaedic surgeons and clinical researchers with methodology to optimize inference and minimize bias in observational studies that are often much more feasible to undertake. To mitigate the risk of bias arising from their nonexperimental design, researchers must first understand the ways in which measured covariates can influence treatment, outcomes, and missingness of follow-up data. With knowledge of these relationships, researchers can then build causal diagrams to best understand how to control sources of bias. Some common techniques for controlling for bias include matching, regression, stratification, and propensity score analysis. Selection bias may result from loss to follow-up and missing data. Strategies such as multiple imputation and time-to-event analysis can be useful for handling missingness. For longitudinal data, repeated measures allow observational studies to best summarize the impact of the intervention over time. Clinical researchers familiar with fundamental concepts of causal inference and techniques reviewed in this article will have the power to improve the quality of inferences made from clinical research in orthopaedic trauma surgery.
Effect of Nirmatrelvir/Ritonavir (Paxlovid) on Hospitalization among Adults with COVID-19: an EHR-based Target Trial Emulation from N3C
Authors: Bhatia Abhishek , Preiss Alexander J. , Xiao Xuya , Brannock M. Daniel , Alexander G. Caleb , Chew Robert F. , Fitzgerald Megan , Hill Elaine , Kelly Elizabeth P. , Mehta Hemalkumar B. , Madlock-Brown Charisse , Wilkins Kenneth J. , Chute Christopher G. , Haendel Melissa , Moffitt Richard , Pfaff Emily R. ,   The N3C Consortium
Published: May 2023

AbstractThis study leverages electronic health record data in the National COVID Cohort Collaborative’s (N3C) repository to investigate disparities in Paxlovid treatment and to emulate a target trial assessing its effectiveness in reducing COVID-19 hospitalization rates. From an eligible population of 632,822 COVID-19 patients seen at 33 clinical sites across the United States between December 23, 2021 and December 31, 2022, patients were matched across observed treatment groups, yielding an analytical sample of 410,642 patients. We estimate a 65% reduced odds of hospitalization among Paxlovid-treated patients within a 28-day follow-up period, and this effect did not vary by patient vaccination status. Notably, we observe disparities in Paxlovid treatment, with lower rates among Black and Hispanic or Latino patients, and within socially vulnerable communities. Ours is the largest study of Paxlovid’s real-world effectiveness to date, and our primary findings are consistent with previous randomized control trials and real-world studies.
What happened to health labour markets during COVID-19? Insights from a survey of medical doctors in Brazil
Authors: Alves de Oliveira Bruno Luciano Carneiro , Scheffer Mário , Cassenote Alex , Russo Giuliano 
Published: May 2023

AbstractBackgroundLimited evidence exists on impacts and adaptations of global health markets during COVID-19. We examined physicians’ perceptions of changing employment opportunities in Brazil, to gain an insight into labour markets in low- and middle-income countries (LMICs) during the pandemic.MethodsWe conducted secondary analysis of a dataset from a representative cross-sectional survey of 1,183 physicians in São Paulo and Maranhão states in Brazil. We estimated prevalence and 95% Confidence Intervals (CI) for proxy variables of demand and supply of doctors, and prices of medical services for facilities of practice in the two States, stratified by public, private, and dual practice physicians.ResultsMost doctors reported increased job opportunities in the public sector (59.0%, 95% CI 56.1-61.9), particularly in Maranhão state (66.4%, 95% CI 62.3-70.3). For the private sector, increased opportunities were reported only in large private hospitals (51.4%, 95% CI 48.4-54.4), but not in smaller clinics. We recorded perceptions of slight increases in availability of doctors in Maranhão, particularly in the public sector (54.1%, 95 CI 45.7-62.3). Younger doctors recounted increased vacancies in the public sector (64%, 95 CI 58.1-68.1); older doctors only in walk-in clinics in Maranhão (47.5%, 95 CI 39.9-55.1). Those working directly with COVID-19 saw opportunities in public hospitals (65%, 95 CI 62.3-68.4), and in large private ones (55%, 95 CI 51.8-59.1)ConclusionsOur findings suggest that health labour markets in (LMICs) may not necessarily shrink during epidemics, and that impacts will depend on the balance of public and private services in national health systems.Key messagesWhat is already known on this topiHealth labour markets are believed to shrink during epidemics, with fewer services and jobs available because of lockdowns and reduced demand.What this study addsThe doctors we surveyed in Brazil noticed increased job opportunities in the public sector during COVID-19, particularly in Maranhão state. For the private sector, increased vacancies were reported in large private hospitals but not in smaller clinics.How this study might affect research, practice or policyThe complementary roles of health markets and publicly or privately funded systems during a health emergency might need re-examining to improve pandemic preparedness in LMICs.
Identification of the conservediolgene cluster involved in rhizosphere competence inPseudomonas
Authors: Sánchez-Gil Juan J. , Poppeliers Sanne W. M. , Vacheron Jordan , Zhang Hao , Odijk Bart , Keel Christoph , de Jonge Ronnie 
Published: May 2023

AbstractThePseudomonasgenus has shown great potential as a sustainable solution to support agriculture through its plant-growth promoting and biocontrol activities. However, their efficacy as bioinoculants is limited by unpredictable colonization in natural conditions. Our study identifies theiollocus, a gene cluster inPseudomonasinvolved in inositol catabolism, as a feature enriched among superior root colonizers in natural soil. Further characterization revealed that theiollocus increases competitiveness by inducing swimming motility and fluorescent siderophore production in response to inositol, a plant-derived compound. Public data analyses indicate that theiollocus is broadly conserved in thePseudomonasgenus and linked to diverse host-microbe interactions. Our findings suggest theiollocus as a potential target for developing more effective bioinoculants, given its conservation and association with diverse host-microbe interactions.
Single-cell mutation rate of turnip crinkle virus (-)-strand replication intermediates
Authors: Carvalho Camila Perdoncini , Han Junping , Khemson Khwannarin , Ren Ruifan , Camargo Luis Eduardo Aranha , Miyashita Shuhei , Qu Feng 
Published: May 2023

AbstractViruses with single-stranded, positive-sense (+) RNA genomes incur high numbers of errors during replication, thereby creating diversified genome populations from which new, better adapted viral variants can emerge. However, a definitive error rate is known for a relatively few (+) RNA plant viruses, due to challenges to account for perturbations caused by natural selection and/or experimental set-ups. To address these challenges, we developed a new approach that exclusively profiled errors in the (-)-strand replication intermediates of turnip crinkle virus (TCV), in singly infected cells. A series of controls and safeguards were devised to ensure errors inherent to the experimental process were accounted for. This approach permitted the estimation of a TCV error rate of 8.47 X 10−5substitution per nucleotide site per cell infection. Importantly, the characteristic error distribution pattern among the 50 copies of 2,363-base-pair cDNA fragments predicted that nearly all TCV (-) strands were products of one replication cycle per cell. Furthermore, some of the errors probably elevated error frequencies by lowering the fidelity of TCV RNA-dependent RNA polymerase, and/or permitting occasional re-replication of progeny genomes. In summary, by profiling errors in TCV (-)-strand intermediates incurred during replication in single cells, this study provided strong support for a stamping machine mode of replication employed by a (+) RNA virus.Author SummaryMost (+) RNA viruses introduce replication errors at relatively high frequencies. As a result, it is of vital importance for these viruses to purge lethal errors in a timely manner. TCV, a plant-infecting small (+) RNA virus, was proposed to encode a Bottleneck, Isolate, Amplify, Select (BIAS) mechanism that compel swift clearance of lethal errors by bottlenecking the number of replicating genome copies to one per cell. A crucial prediction of this BIAS model is that such bottlenecking also acts on progeny genome copies, preventing them from repeating replication in the cells of their own genesis. The current study tested this prediction by developing a carefully controlled, readily reproducible approach to profile errors and error distributions in (-)-stranded replication intermediates of TCV. We found that most of replication-generated (-) strands descended from the primary (+) strands through a single replication cycle. This finding adds fresh support to the BIAS model.
Structural and functional insights in flavivirus NS5 proteins gained by the structure of Ntaya virus polymerase and methyltransferase
Authors: Krejčová Kateřina , Krafcikova Petra , Klima Martin , Chalupska Dominika , Chalupsky Karel , Zilecka Eva , Boura Evzen 
Published: May 2023

AbstractFlaviviruses are single-stranded positive-sense RNA (+RNA) viruses that are responsible for several (re)emerging diseases such as Yellow, Dengue or West Nile fevers. The Zika epidemic highlighted their dangerousness when a relatively benign virus known since the 1950s turned into a deadly pathogen. The central protein for their replication is NS5 (non-structural protein 5), which is composed of the N-terminal methyltransferase (MTase) domain and the C-terminal RNA-dependent RNA-polymerase (RdRp) domain. It is responsible for both, RNA replication and installation of the 5’ RNA cap. We structurally and biochemically analyzed the Ntaya virus MTase and RdRp domains and we compared their properties to other flaviviral NS5s. The enzymatic centers are well conserved acrossFlaviviridae, suggesting that the development of drugs targeting all flaviviruses is feasible. However, the enzymatic activities of the isolated proteins were significantly different for the MTase domains.
Chlamydomonas reinhardtii and Microbacterium forte sp. nov.,a mutualistic association that favor sustainable hydrogen production
Authors: Fakhimi Neda , Torres María Jesus , Fernandez Emilio , Galván Aurora , Dubini Alexandra , González-Ballester David 
Published: May 2023

AbstractA multispecies bacterial community includingMicrobacterium fortesp. nov.,Stenotrophomonas goyisp. nov., andBacillus cereusgreatly promoted sustained hydrogen production by the microalgaChlamydomonas reinhardtiiwhen cocultivated in mannitol- and yeast extract-containing medium (up to 313 mL·L-1). Alga viability was also largely prolonged in the cocultures (>45 days) without any nutrient supplementation. Among the bacterial community,Microbacterium fortesp. nov. was the main responsible for the hydrogen production improvement. Nonetheless, the use of the entire bacterial community allowed a better growth of the alga during hydrogen production.Chlamydomonas reinhardtiiandMicrobacterium fortesp. nov. established a mutualistic association, based on the release of ammonium and acetic acid from the bacterium, while the alga provided sulfur-containing metabolites and complemented the bacterial auxotrophy for biotin and thiamine. This study uncovers the potential of the Chlamydomonas-bacteria consortia for durable and stable H2production while allowing the simultaneous production of biomass.
Evolutionary Insights from a Large-scale Survey of Population-genomic Variation
Authors: Ye Zhiqiang , Wei Wen , Pfrender Michael , Lynch Michael 
Published: May 2023

AbstractResults from data on>1000 haplotypes distributed over a nine-year period from a natural population of the microcrustaceanDaphnia pulexreveal evolutionary-genomic features at a refined scale, including key population-genetic properties that are obscured in studies with smaller sample sizes. Background selection, resulting from the recurrent introduction of dele-terious alleles, appears to strongly influence the dynamics of neutral alleles, inducing indirect negative selection on rare variants and positive selection on common variants. Fluctuating selection increases the persistence of nonsynonymous alleles with intermediate frequencies, while reducing standing levels of variation at linked silent sites. Combined with the results from an equally large metapopulation survey of the study species, regions of gene structure that are under strong purifying selection and classes of genes that are under strong positive selection in this key species can be confidently identified. Most notable among rapidly evolvingDaph-niagenes are those associated with ribosomes, mitochondrial functions, sensory systems, and lifespan determination.
ADARs regulate cuticle collagen expression to promote survival to pathogen infection
Authors: Dhakal Alfa , Salim Chinnu , Skelly Mary , Amichan Yarden , Lamm Ayelet T. , Hundley Heather A. 
Published: May 2023

AbstractBackgroundIn all organisms, the innate immune system defends against pathogens through basal expression of molecules that provide critical barriers to invasion and inducible expression of effectors that combat infection. The adenosine deaminase that act on RNA (ADAR) family of RNA binding proteins has been reported to influence innate immunity in metazoans. However, studies on the susceptibility of ADAR mutant animals to infection are largely lacking.ResultsHere, by analyzingadr-1andadr-2null mutants in well-established slow-killing assays, we find that bothCaenorhabditis elegansADARs are important for organismal survival to gram-negative and gram-positive bacteria, all of which are pathogenic to humans. Furthermore, our high-throughput sequencing and genetic analysis reveal that ADR-1 and ADR-2 function in the same pathway to regulate collagen expression. Consistent with this finding, our scanning electron microscopy studies indicateadr-1;adr-2mutant animals also have altered cuticle morphology prior to pathogen exposure.ConclusionsOur data uncover a critical role of theC. elegansADAR family of RNA binding proteins in promoting cuticular collagen expression, which represents a new post-transcriptional regulatory node that influences the extracellular matrix. In addition, we provide the first evidence that ADAR mutant animals have altered susceptibility to infection with several opportunistic human pathogens, suggesting a broader role of ADARs in altering physical barriers to infection to influence innate immunity.
Parallel genome-scale CRISPR-Cas9 screens uncouple human pluripotent stem cell identity versus fitness
Authors: Rosen Bess P. , Li Qing V. , Cho Hyein S. , Liu Dingyu , Yang Dapeng , Graff Sarah , Yan Jielin , Luo Renhe , Verma Nipun , Damodaran Jeyaram R. , Kale Hanuman T. , Kaplan Samuel J. , Beer Michael A. , Sidoli Simone , Huangfu Danwei 
Published: May 2023

AbstractPluripotent stem cells are defined by their self-renewal capacity, which is the ability of the stem cells to proliferate indefinitely while maintaining the pluripotent identity essential for their ability to differentiate into any somatic cell lineage. However, understanding the mechanisms that control stem cell fitness versus the pluripotent cell identity is challenging. To investigate the interplay between these two aspects of pluripotency, we performed four parallel genome-scale CRISPR-Cas9 loss-of-function screens interrogating stem cell fitness in hPSC self-renewal conditions, and the dissolution of the primed pluripotency identity during early differentiation. Comparative analyses led to the discovery of genes with distinct roles in pluripotency regulation, including mitochondrial and metabolism regulators crucial for stem cell fitness, and chromatin regulators that control pluripotent identity during early differentiation. We further discovered a core set of factors that control both stem cell fitness and pluripotent identity, including a network of chromatin factors that safeguard pluripotency. Our unbiased and systematic screening and comparative analyses disentangle two interconnected aspects of pluripotency, provide rich datasets for exploring pluripotent cell identity versus cell fitness, and offer a valuable model for categorizing gene function in broad biological contexts.
Engineering of a biosensor for intracellular aspartate
Authors: Hellweg Lars , Pfeifer Martin , Chang Lena , Tarnawski Miroslaw , Bergner Andrea , Kress Jana , Hiblot Julien , Reinhardt Jürgen , Johnsson Kai , Leippe Philipp 
Published: May 2023

ABSTRACTAspartate is a limiting metabolite in proliferating cells with its production closely linked to glutamine and mitochondrial metabolism. To date, measuring aspartate concentrations in live cells was deemed impossible. We present iAspSnFR, a genetically-encoded biosensor for intracellular aspartate, engineered by displaying and screening biosensor libraries in HEK293 cells. In live cells, iAspSnFR exhibits a dynamic range of 130% fluorescence change and detects reduced aspartate levels upon glutamine deprivation or glutaminase inhibition. Furthermore, iAspSnFR tracks aspartate uptake by excitatory amino acid transporters, or of asparagine after co-expression of an asparaginase. Importantly, iAspSnFR reports aspartate depletions upon electron transport chain inhibition, and therefore it can serve as a proxy for mitochondrial respiration. Consequently, iAspSnFR can dissect the major cellular pathways of aspartate production, offering immediate applications, particularly in cancer biology, such as screening small molecules targeting aspartate and glutamine metabolism.
ARID1B controls transcriptional programs of axon projection in the human corpus callosum
Authors: Martins-Costa Catarina , Pham Vincent A. , Wiegers Andrea , Sidhaye Jaydeep , Doleschall Balint , Novatchkova Maria , Lendl Thomas , Piber Marielle , Peer Angela , Möseneder Paul , Stuempflen Marlene , Chow Siu Yu A. , Seidl Rainer , Prayer Daniela , Höftberger Romana , Kasprian Gregor , Ikeuchi Yoshiho , Corsini Nina S. , Knoblich Jürgen A. 
Published: May 2023

AbstractMutations inARID1B, a member of the mSWI/SNF complex, cause severe neurodevelopmental phenotypes with elusive mechanisms in humans. The most common structural abnormality in the brain of ARID1B patients is agenesis of the corpus callosum (ACC). This condition is characterized by a partial or complete absence of the corpus callosum (CC), an interhemispheric white matter tract that connects distant cortical regions. Using human neural organoids, we identify a vulnerability of callosal projection neurons (CPNs) toARID1Bhaploinsufficiency, resulting in abnormal maturation trajectories and dysregulation of transcriptional programs of CC development. Through a novelin vitromodel of the CC tract, we demonstrate thatARID1Bmutations reduce the proportion of CPNs capable of forming long-range projections, leading to structural underconnectivity phenotypes. Our study uncovers new functions of the mSWI/SNF during human corticogenesis, identifying cell-autonomous defects in axonogenesis as a cause of ACC in ARID1B patients.Abstract FigureGraphical abstractHuman callosal projection neurons are vulnerable toARID1Bhaploinsufficiency.(Top)During healthy development, callosal projection neurons (CPNs) project long interhemispheric axons, forming the corpus callosum (CC) tract, which can be modeledin vitro.(Bottom)In ARID1B patients, transcriptional dysregulation of genetic programs of CC development reduces the formation of long-range projections from CPNs, causing CC agenesisin vivoand underconnectivity phenotypesin vitro.
Critical exploration of AI-driven HRM to build up organizational capabilities
Authors: Böhmer Nicole , Schinnenburg Heike 
Published: May 2023

PurposeHuman resource management (HRM) processes are increasingly artificial intelligence (AI)-driven, and HRM supports the general digital transformation of companies' viable competitiveness. This paper points out possible positive and negative effects on HRM, workplaces and workers’ organizations along the HR processes and its potential for competitive advantage in regard to managerial decisions on AI implementation regarding augmentation and automation of work.Design/methodology/approachA systematic literature review that includes 62 international journals across different disciplines and contains top-tier academic and German practitioner journals was conducted. The literature analysis applies the resource-based view (RBV) as a lens through which to explore AI-driven HRM as a potential source of organizational capabilities.FindingsThe analysis shows four ambiguities for AI-driven HRM that might support sustainable company development or might prevent AI application: job design, transparency, performance and data ambiguity. A limited scholarly discussion with very few empirical studies can be stated. To date, research has mainly focused on HRM in general, recruiting and HR analytics in particular.Research limitations/implicationsThe four ambiguities' context-specific potential for capability building in firms is indicated, and research avenues are developed.Originality/valueThis paper critically explores AI-driven HRM and structures context-specific potential for capability building along four ambiguities that must be addressed by HRM to strategically contribute to an organization's competitive advantage.