bluuebunny/crossref_metadata_2025_split huggingface dataset:
Sex differences and immune correlates of Long COVID development, persistence, and resolution
Authors: Hamlin Rebecca E. , Pienkos Shaun M. , Chan Leslie , Stabile Mikayla A. , Pinedo Kassandra , Rao Mallika , Grant Philip , Bonilla Hector , Holubar Marisa , Singh Upinder , Jacobson Karen B. , Jagannathan Prasanna , Maldonado Yvonne , Holmes Susan P. , Subramanian Aruna , Blish Catherine A. 
Published: June 2024

AbstractSex differences have been observed in acute COVID-19 and Long COVID (LC) outcomes, with greater disease severity and mortality during acute infection in males and a greater proportion of females developing LC. We hypothesized that sex-specific immune dysregulation contributes to the pathogenesis of LC. To investigate the immunologic underpinnings of LC development and persistence, we used single-cell transcriptomics, single-cell proteomics, and plasma proteomics on blood samples obtained during acute SARS-CoV-2 infection and at 3 and 12 months post-infection in a cohort of 45 patients who either developed LC or recovered. Several sex-specific immune pathways were associated with LC. Specifically, males who would develop LC at 3 months had widespread increases inTGF-βsignaling during acute infection in proliferating NK cells. Females who would develop LC demonstrated increased expression ofXIST, an RNA gene implicated in autoimmunity, and increasedIL1signaling in monocytes at 12 months post infection. Several immune features of LC were also conserved across sexes. Both males and females with LC had reduced co-stimulatory signaling from monocytes and broad upregulation ofNF-κBtranscription factors. In both sexes, those with persistent LC demonstrated increased LAG3, a marker of T cell exhaustion, reducedETS1transcription factor expression across lymphocyte subsets, and elevated intracellular IL-4 levels in T cell subsets, suggesting that ETS1 alterations may drive an aberrantly elevated Th2-like response in LC. Altogether, this study describes multiple innate and adaptive immune correlates of LC, some of which differ by sex, and offers insights toward the pursuit of tailored therapeutics.One Sentence SummaryThis multi-omic analysis of Long COVID reveals sex differences and immune correlates of Long COVID development, persistence, and resolution.
The Establishment and Potential Spread ofOsmia cornuta(Hymenoptera: Megachilidae) in North America
Authors: Getz Michael P , Best Lincoln R , Melathopoulos Andony P , Warren Timothy L 
Published: June 2024

AbstractMason bees, subgenusOsmiaPanzer (Hymenoptera: Megachilidae), are economically and ecologically significant pollinators. In eastern North America, the rapid spread of two non-native species from Asia,O. cornifronsRadoszkowski andO. taurusSmith, has coincided with declines in nativeOsmiapopulations, raising concern about the effects of further exotic invasions. Here we investigate the recent establishment in British Columbia, Canada of the European orchard bee,O. cornutaLatreille, previously thought to be limited to Europe and its periphery. We documentO. cornutarecords ranging over 170 km, including sightings of live adults and the discovery of a multigenerational nest with hundreds of cocoons. We tested whether theseO. cornutacocoons could be discriminated from otherOsmiaspecies by training a machine learning classifier on features extracted from images. The best performing model could not reliably discriminate cocoons by species, raising the possibilityO. cornutacould be inadvertently intermingled in future commercial shipments. Spatially isolated records ofO. cornifronsandO. taurusfurther suggest ongoing anthropogenic dispersal of these species. To determine environmentally suitable regions forO. cornutato spread in North America, we estimated its climate niche using native-range occurrence data. This analysis indicated broad regions of the Pacific Northwest and eastern North America contain potentially suitable habitat. Together, our findings document the establishment ofO. cornutain North America and the potential for it to spread broadly. Our study demonstrates the utility of accessible biodiversity data archives and public observation programs in tracking biological invasions and highlights the need for future monitoring of exoticOsmia.
Reduction of fungal dysbiosis is involved in the attenuation of Dextran Sodium Sulfate-Induced Mouse Colitis Mediated by GILZ protein and yeast extract compound
Authors: Gentili Marco , Nunzi Emilia , Sabbatini Samuele , Lusenti Eleonora , Cari Luigi , Mencacci Antonella , Ballet Nathalie , Migliorati Graziella , Riccardi Carlo , Ronchetti Simona , Monari Claudia 
Published: June 2024

ABSTRACTInflammatory bowel diseases (IBD), such as Crohn’s disease and ulcerative colitis, have a complex and multifactorial pathogenesis that remains not fully elucidated. Recent research suggests that intestinal fungal dysbiosis may contribute to the development and persistence of IBD. In this study, we explored, for the first time, the effects of the glucocorticoid-induced leucine zipper (GILZ) protein, known to have protective effects on the gut mucosa in preclinical IBD models, in combination with a yeast extract, which supports the growth of beneficial microorganisms, in a mouse model of ulcerative colitis. The combined treatment produced significant protection against severe disease outcomes in the mice, including the restoration of intestinal barrier integrity and the reduction of pro-inflammatory cytokines. Specifically, GILZ primarily acted on the gut permeability, while the yeast extract mainly reduced pro-inflammatory cytokines. Notably, both treatments were effective in restoring the intestinal burden of clinically importantCandidaand formerCandidaspecies. Analysis of the intestinal fungal communities revealed that both treatments were able to reduce colitis-associated fungal dysbiosis, promoting a fungal composition similar to that of healthy mice. This effect was mainly the result of a decreased abundance of theMeyerozimagenus, which was dominant in the colitic mice. Thus, combined treatment regimens with the GILZ protein and yeast extract could represent a new strategy for the treatment of inflammatory bowel diseases, by targeting multiple mechanisms at the basis of IBD, including the fungal dysbiosis.IMPORTANCEInflammatory bowel diseases (IBD), including Crohn’s disease and ulcerative colitis, are characterized by chronic inflammation and have a complex, multifactorial pathogenesis that is not yet fully understood. Currently, no established therapeutic strategy can consistently manage IBD effectively. Recent research indicates that intestinal fungal dysbiosis could potentially contribute to the development and persistence of chronic IBD, highlighting the importance of investigating alternative therapeutic strategies able to attenuate fungal dysbiosis in the context of intestinal inflammation. In this study, we demonstrate that a combination of a recombinant protein (GILZp) and a compound with prebiotic properties could represent a new therapeutic strategy for the treatment of IBD, as it not only decreases inflammation and restores the integrity of the epithelial barrier, but reduces fungal dysbiosis associated with DSS-induced colitis.
Exploring self-reported quality of life in developmental language disorder
Authors: Larson Caroline 
Published: June 2024

AbstractPurposeDevelopmental language disorder (DLD) is a lifelong condition associated with poorer outcomes than neurotypical peers, yet relatively little is known about long-term quality of life in DLD. This preliminary study adopts a neurodiversity-informed approach by exploringself-reportedquality of life in an adolescent and young adult DLD sample, as well as linguistic and risk factors contributing to quality of life.MethodParticipants were five individuals with DLD aged 12-20 years (M = 15.60; SD = 3.05). I administered two self-report quality of life scales, a language assessment, an experimental morphosyntax task, and measures of risk factors. Data were analyzed descriptively.ResultsParticipants generally reported positive views about their quality of life, though accessing accommodations and health services emerged as barriers. Relatively better grammaticality judgement performance appeared to be linked with poorer ratings of happiness and the ability to ‘be yourself.’ Nonverbal ability represented a potential risk factor, though there may be a stronger cumulative role for risk factors.ConclusionsDLD participants reported relatively good quality of life. Exploratory findings suggest barriers to quality of life in some contexts, as well as roles for individual differences in language and risk factors. These descriptive findings should be examined in larger scale studies and may represent areas of consideration when clinicians address functional challenges that impact mental health and wellbeing in individuals with DLD.
Minimizing biological risk for novel inhibitory drug targets: One knockout is all you need
Authors: Dimitriev Alan , Postovit Lynne-Marie , Simpson Amber L. , Wong Gane Ka-Shu 
Published: June 2024

AbstractWe argue that biological risk for novel inhibitory drug targets can be minimized, almost eliminated, by a computational analysis of the healthcare records and DNA sequences in resources like UK Biobank or All-of-Us. The key insight is that an inhibitory drug is functionally equivalent to a loss-of-function (LOF) variant in the targeted gene. It is a special case of what has been called an “experiment of nature”. To demonstrate, we considered all available clinical trials (58 in total) and inhibitory drugs (15 in total) for 5 cardiovascular drug targets: PCSK9, APOC3, ANGPTL3, LPA, and ASGR1. The results were shocking. Every biomarker assessed in these clinical trials was successfully predicted, i.e. directionality and proportionality of effect, but not the magnitude since that varies with dosage. This concept has not been widely adopted because geneticists believe that homozygous LOFs, which are exceedingly rare, would be needed to observe a significant phenotypic effect from most genetic knockouts. Our study shows that, to the contrary, given a sufficiently large biobank, counting both carriers and non-carriers, heterozygous LOFs alone can inform drug development.
Augmenting maternal clinical cohort data with administrative laboratory dataset linkages: a validation study
Authors: Rossouw Laura , Ngcobo Nkosinathi , Clouse Kate , Nattey Cornelius , Technau Karl-Günter , Maskew Mhairi 
Published: June 2024

AbstractBackgroundThe use of big data and large language models in healthcare can play a key role in improving patient treatment and healthcare management, especially when applied to large-scale administrative data. A major challenge to achieving this is ensuring that patient confidentiality and personal information is protected. One way to overcome this is by augmenting clinical data with administrative laboratory dataset linkages in order to avoid the use of demographic information.MethodsWe explored an alternative method to examine patient files from a large administrative dataset in South Africa (the National Health Laboratory Services, or NHLS), by linking external data to the NHLS database using specimen barcodes associated with laboratory tests. This offers us with a deterministic way of performing data linkages without accessing demographic information. In this paper, we quantify the performance metrics of this approach.ResultsThe linkage of the large NHLS data to external hospital data using specimen barcodes achieved a 95% success. Out of the 1200 records in the validation sample, 87% were exact matches and 9% were matches with typographic correction. The remaining 5% were either complete mismatches or were due to duplicates in the administrative data.ConclusionsThe high success rate indicates the reliability of using barcodes for linking data without demographic identifiers. Specimen barcodes are an effective tool for deterministic linking in health data, and may provide a method of creating large, linked data sets without compromising patient confidentiality.
Network meta-analysis made simple: a composite likelihood approach
Authors: Liu Yu-Lun , Zhang Bingyu , Chu Haitao , Chen Yong 
Published: June 2024

AbstractNetwork meta-analysis, also known as mixed treatments comparison meta-analysis or multiple treatments meta-analysis, extends conventional pairwise meta-analysis by simultaneously synthesizing multiple interventions in a single integrated analysis. Despite the growing popularity of network meta-analysis within comparative effectiveness research, it comes with potential challenges. For example, within-study correlations among treatment comparisons are rarely reported in the published literature. Yet, these correlations are pivotal for valid statistical inference. As demonstrated in earlier studies, ignoring these correlations can inflate mean squared errors of the resulting point estimates and lead to inaccurate standard error estimates. This paper introduces a composite likelihood-based approach that ensures accurate statistical inference without requiring knowledge of the within-study correlations. The proposed method is computationally robust and efficient, with substantially reduced computational time compared to the state-of-the-science methods implemented in R packages. The proposed method was evaluated through extensive simulations and applied to two important applications including a network meta-analysis comparing interventions for primary open-angle glaucoma, and another comparing treatments for chronic prostatitis and chronic pelvic pain syndrome.HighlightsWhat is already known?Network meta-analysis extends conventional pairwise meta-analysis by simultaneously synthesizing multiple interventions in a single integrated analysis.A significant challenge in network meta-analysis is the lack of reported within-study correlations among treatment comparisons in the published studies.What is new?We propose a new method for network meta-analysis that ensures vaild statistical inference without the need for knowledge of within-study correlations.The proposed method employs a composite likelihood and a sandwich-type robust variance estimator, offering a computationally efficient and scalable solution, particularly for network meta-analysis with a large number of treatments and studies.Potential impact forResearch Synthesis MethodsreadersThe proposed method can be easily applied to any univariate network meta-analysis project without requiring knowledge of within-study correlations among treatment comparisons.
Patient and public experience and views on digital systems for sharing records for health and care preferences at the end of life
Authors: Birtwistle J. , Russell AM , Relton S. , Easdown H. , Grieve U. , Allsop M. 
Published: June 2024

AbstractObjectiveTo explore patient and public experiences of and priorities for the use of shared patient health records for advance care planning.MethodsA convergent-parallel mixed method design was used. An online national survey of patients and the public gathered data on experiences and views of sharing health and advance care planning information to support care at the end of life. Descriptive statistics were used to analyse rating scale responses (5 or 10-point scale) and thematic analysis applied to free-text responses.ResultsResponses (N=1728) included participants in 103 UK counties, including people with a terminal condition (n=33), long-term condition (n=442), who provide or have provided care to a person with a long-term or terminal illness (n=229), and who identified as healthy and interested in planning for the future (n=1024). Confidence that recorded care preferences would be accessed when needed was low for carers (median= 2, IQR 1-4) and moderate for patients (median=3, IQR 1-4). Four themes derived from free-text responses included: i) Experience of sharing health information; ii) Preparation, communication and understanding; iii) Concerns, unknowns and assurance seeking, and; iv) Preserving Dignity and Respect: Understanding individual contexts.ConclusionsWhilst recognising the potential of sharing health records, respondents and in particular carers, doubted that patient information would be accessed by relevant health professionals when needed. Future research is required to explore whether patient and carer access to the record influences their confidence in the accuracy of the content and the likelihood of care being delivered in line with their wishes.What is already known on this topicDigital systems can support documentation and sharing of health information, wishes and preferences for the end of life.What this study addsPatients and carers perceive the documentation of advance care plans as a burdensome and complex process, that can lead to confusion about the purpose of documentation.Respondents expressed doubts about the accuracy of documented information, uncertainty about whether health professionals could access their records when needed and concerns that documented wishes and preferences would be ignored.How this study might affect research, practice or policyPatient and public views must be considered in the design and implementation of digital systems. In particular, efforts should be made to build confidence and clarify the expectations of patients and members of the public around the documentation of their wishes and preferences for care alongside the subsequent sharing and use of this information.
From emergence to endemicity: highly pathogenic H5 avian influenza viruses in Taiwan
Authors: Li Yao-Tsun , Ko Hui-Ying , Hughes Joseph , Liu Ming-Tsan , Lin Yi-Ling , Hampson Katie , Brunker Kirstyn 
Published: June 2024

AbstractA/goose/Guangdong/1/96-like (GsGd) highly pathogenic avian influenza (HPAI) H5 viruses cause severe outbreaks in poultry when introduced. Since emergence in 1996, control measures in most countries have suppressed local GsGd transmission following introductions, making persistent transmission in domestic birds rare. However, geographical expansion of clade 2.3.4.4 sublineages has raised concern about establishment of endemic circulation, while mechanistic drivers leading to endemicity remain unknown. We reconstructed the evolutionary history of GsGd sublineage, clade 2.3.4.4c, in Taiwan using a time-heterogeneous rate phylogeographic model. During Taiwan’s initial epidemic wave (January 2015 - August 2016), we inferred that localised outbreaks had multiple origins from rapid spread between counties/cities nationwide. Subsequently, outbreaks predominantly originated from a single county, Yunlin, where persistent transmission harbours the trunk viruses of the sublineage. Endemic hotspots determined by phylogeographic reconstruction largely predicted the locations of re-emerging outbreaks in Yunlin. The transition to endemicity involved a shift to chicken-dominant circulation, following the initial bidirectional spread between chicken and domestic waterfowl. Our results suggest that following their emergence in Taiwan, source-sink dynamics from a single county have maintained GsGd endemicity, pointing to where control efforts should be targeted to eliminate the disease.
Clonal hematopoiesis of indeterminate potential contributes to accelerated chronic kidney disease progression
Authors: Vlasschaert Caitlyn , Pan Yang , Chen Jianchun , Akwo Elvis , Rao Varun , Hixson James E. , Chong Michael , Uddin Md Mesbah , Yu Zhi , Jiang Mengdi , Peng Fenfen , Cao Shirong , Wang Yinqiu , Kim Do-Kyun , Hung Adriana M. , He Jing , Tamura Manjula Kurella , Cohen Debbie L. , He Jiang , Li Changwei , Bhat Zeenat , Rao Panduranga , Xie Dawei , Bick Alexander G. , Kestenbaum Bryan , Paré Guillaume , Rauh Michael J. , Levin Adeera , Natarajan Pradeep , Lash James P. , Zhang Ming-Zhi , Harris Raymond C. , Robinson-Cohen Cassianne , Lanktree Matthew B. , Kelly Tanika N. ,   the CRIC Study Investigators
Published: June 2024

AbstractBackgroundClonal hematopoiesis of indeterminate potential (CHIP) is a common inflammatory condition of aging that causes myriad end-organ damage. We have recently shown associations for CHIP with acute kidney injury and with kidney function decline in the general population, with stronger associations for CHIP driven by mutations in genes other thanDNMT3A(non-DNMT3ACHIP). Longitudinal kidney function endpoints in individuals with pre-existing chronic kidney disease (CKD) and CHIP have been examined in two previous studies, which reported conflicting findings and were limited by small sample sizes.MethodsIn this study, we examined the prospective associations between CHIP and CKD progression events in four cohorts of CKD patients (total N = 5,772). The primary outcome was a composite of 50% kidney function decline or kidney failure. The slope of eGFR decline was examined as a secondary outcome. Mendelian randomization techniques were then used to investigate potential causal effects of CHIP on eGFR decline. Finally, kidney function was assessed in adenine-fed CKD model mice having received a bone marrow transplant recapitulatingTet2-CHIP compared to controls transplanted wild-type bone marrow.ResultsAcross all cohorts, the average age was 66.4 years, the average baseline eGFR was 42.6 ml/min/1.73m2, and 24% had CHIP. Upon meta-analysis, non-DNMT3ACHIP was associated with a 59% higher relative risk of incident CKD progression (HR 1.59, 95% CI: 1.02-2.47). This association was more pronounced among individuals with diabetes (HR 1.29, 95% CI: 1.03-1.62) and with baseline eGFR ≥ 30 ml/min/1.73m (HR 1.80, 95% CI: 1.11-2.90). Additionally, the annualized slope of eGFR decline was steeper among non-DNMT3ACHIP carriers, relative to non-carriers (β -0.61 ± 0.31 ml/min/1.73m2, p = 0.04). Mendelian randomization analyses suggested a causal role for CHIP in eGFR decline among individuals with diabetes. In a dietary adenine mouse model of CKD,Tet2-CHIP was associated with lower GFR as well as greater kidney inflammation, tubular injury, and tubulointerstitial fibrosis.ConclusionNon-DNMT3ACHIP is a potentially targetable novel risk factor for CKD progression.