bluuebunny/crossref_metadata_2025_split huggingface dataset:
The causal effect of Alzheimer’s disease and family history of Alzheimer’s disease on non-ischemic cardiomyopathy and left ventricular structure and function: a Mendelian randomization study
Authors: Li Zhenjie , Chen Xiandong , He Wangping , Chen Huazeng , Chen Dehai 
Published: June 2024

BackgroundPrevious studies have shown that Alzheimer’s disease (AD) can cause myocardial damage. However, whether there is a causal association between AD and non-ischemic cardiomyopathy (NICM) remains unclear. Using a comprehensive two-sample Mendelian randomization (MR) method, we aimed to determine whether AD and family history of AD (FHAD) affect left ventricular (LV) structure and function and lead to NICM, including hypertrophic cardiomyopathy (HCM) and dilated cardiomyopathy (DCM).MethodsThe summary statistics for exposures [AD, paternal history of AD (PH-AD), and maternal history of AD (MH-AD)] and outcomes (NICM, HCM, DCM, and LV traits) were obtained from the large European genome-wide association studies. The causal effects were estimated using inverse variance weighted, MR-Egger, and weighted median methods. Sensitivity analyses were conducted, including Cochran’s Q test, MR-Egger intercept test, MR pleiotropy residual sum and outlier, MR Steiger test, leave-one-out analysis, and the funnel plot.ResultsGenetically predicted AD was associated with a lower risk of NICM [odds ratio (OR) 0.9306, 95% confidence interval (CI) 0.8825–0.9813, p = 0.0078], DCM (OR 0.8666, 95% CI 0.7752–0.9689, p = 0.0119), and LV remodeling index (OR 0.9969, 95% CI 0.9940–0.9998, p = 0.0337). Moreover, genetically predicted PH-AD was associated with a decreased risk of NICM (OR 0.8924, 95% CI 0.8332–0.9557, p = 0.0011). MH-AD was also strongly associated with a decreased risk of NICM (OR 0.8958, 95% CI 0.8449–0.9498, p = 0.0002). Different methods of sensitivity analysis demonstrated the robustness of the results.ConclusionOur study revealed that AD and FHAD were associated with a decreased risk of NICM, providing a new genetic perspective on the pathogenesis of NICM.
Delivery of a national prenatal exome sequencing service in England: a mixed methods study exploring healthcare professionals’ views and experiences
Authors: Peter Michelle , Mellis Rhiannon , McInnes-Dean Hannah , Daniel Morgan , Walton Holly , Fisher Jane , Leeson-Beevers Kerry , Allen Stephanie , Baple Emma L. , Beleza-Meireles Ana , Bertoli Marta , Campbell Jennifer , Canham Natalie , Cilliers Deirdre , Cobben Jan , Eason Jacqueline , Harrison Victoria , Holder-Espinasse Muriel , Male Alison , Mansour Sahar , McEwan Alec , Park Soo-Mi , Smith Audrey , Stewart Alison , Tapon Dagmar , Vasudevan Pradeep , Williams Denise , Wu Wing Han , Chitty Lyn S. , Hill Melissa 
Published: June 2024

IntroductionIn October 2020, rapid prenatal exome sequencing (pES) was introduced into routine National Health Service (NHS) care in England, requiring the coordination of care from specialist genetics, fetal medicine (FM) and laboratory services. This mixed methods study explored the experiences of professionals involved in delivering the pES service during the first 2 years of its delivery in the NHS.MethodsA survey (n = 159) and semi-structured interviews (n = 63) with healthcare professionals, including clinical geneticists, FM specialists, and clinical scientists (interviews only) were used to address: 1) Views on the pES service; 2) Capacity and resources involved in offering pES; 3) Awareness, knowledge, and educational needs; and 4) Ambitions and goals for the future.ResultsOverall, professionals were positive about the pES service with 77% rating it as Good or Excellent. A number of benefits were reported, including the increased opportunity for receiving actionable results for parental decision-making, improving equity of access to genomic tests and fostering close relationships between FM and genetics departments. Nonetheless, there was evidence that the shift to offering pES in a clinical setting had brought some challenges, such as additional clinic time, administrative processes, perceived lack of autonomy in decision-making regarding pES eligibility and difficulty engaging with peripheral maternity units. Concerns were also raised about the lack of confidence and gaps in genomics knowledge amongst non-genetics professionals - especially midwives. However, the findings also highlighted value in both FM, obstetric and genetics professionals benefiting from further training with a focus on recognising and managing prenatally diagnosed genetic conditions.ConclusionHealthcare professionals are enthusiastic about the benefits of pES, and through multi-collaborative working, have developed relationships that have contributed to effective communication across specialisms. Although limitations on resources and variation in knowledge about pES have impacted service delivery, professionals were hopeful that improvements to infrastructure and the upskilling of all professionals involved in the pathway would optimise the benefits of pES for both parents and professionals.
Immune cell populations and induced immune responses at admission in patients hospitalized with vaccine breakthrough SARS-CoV-2 infections
Authors: Sejdic Adin , Hartling Hans Jakob , Holler Jon Gitz , Klingen Gjærde Lars , Lindegaard Birgitte , Dungu Arnold Matovu , Gnesin Filip , Møller Maria Elizabeth Engel , Teglgaard Rebecca Svanberg , Niemann Carsten Utoft , Brooks Patrick Terrence , Jørgensen Charlotte Sværke , Franck Kristina Træholt , Fischer Thea K. , Marquart Hanne Vibeke , Harboe Zitta Barrella , Ostrowski Sisse Rye 
Published: June 2024

BackgroundVaccine breakthrough SARS-CoV-2 infections are common and of clinical and public health concern. However, little is known about the immunological characteristics of patients hospitalized due to these infections. We aimed to investigate and compare immune cell subpopulations and induced immune responses in vaccinated and non-vaccinated patients hospitalized with severe COVID-19.MethodsA nested case-control study on adults (≥ 18 years) who received at least two doses of a mRNA-COVID-19 vaccine and were hospitalized with SARS-CoV-2 breakthrough infections and severe COVID-19 between January 7, 2021, and February 1, 2022, were eligible for inclusion. Age- and sex-matched non-vaccinated controls were identified. Immunophenotyping was performed using a custom-designed 10-color flow cytometry prefabricated freeze-dried antibody panel (DuraClone, Beckman Coulter (BC), Brea, Calif). TruCulture (Myriad RBM, Austin, USA) was used to assess induced immune response in whole blood, revealing different critical signaling pathways as a proxy for immune function. All samples were obtained within 48 hours of admission.ResultsIn total, 20 hospitalized patients with severe COVID-19 and a breakthrough SARS-CoV-2 infection were included, ten vaccinated and ten non-vaccinated patients. Vaccinated patients had lower concentrations of CD19 B cells (p = 0.035), naïve CD4 T cells (p = 0.015), a higher proportion of γδ1 T cells (p = 0.019), and higher unstimulated immune cell release of IL-10 (p = 0.015).ConclusionWe observed immunological differences between vaccinated and non-vaccinated patients hospitalized due to severe COVID-19 that indicate that vaccinated patients had lower B cell concentrations, lower concentrations of CD4 naïve T cells, a skewed gamma-delta V1/V2 ratio, and an exaggerated IL-10 response at admission. These results could indicate a suboptimal immune response involved in SARS-CoV-2 breakthrough infections that cause severe COVID-19 in vaccinated adults. However, the sample size was small, and further research is needed to confirm these results.
Evaluating the link between immune characteristics and attention deficit hyperactivity disorder through a bi-directional Mendelian randomization study
Authors: Jue Hu , Dan-fei Chen , Fang-fang Li , Ke-pin Yu , Jia-ye Xu , Hui-ting Zhang , Xiao-bo Xuan , Jian Chen 
Published: June 2024

ContextDespite the recognition of attention deficit hyperactivity disorder (ADHD) as a multifaceted neurodevelopmental disorder, its core causes are still ambiguous. The objective of this study was to explore if the traits of circulating immune cells contribute causally to susceptibility to ADHD.MethodsBy employing a unified GWAS summary data covering 731 immune traits from the GWAS Catalog (accession numbers from GCST0001391 to GCST0002121), our analysis focused on the flow cytometry of lymphocyte clusters, encompassing 3,757 Sardinians, to identify genetically expected immune cells. Furthermore, we obtained summarized GWAS statistics from the Psychiatric Genomics Consortium to evaluate the genetic forecasting of ADHD. The studies employed ADHD2019 (20,183 cases and 35,191 controls from the 2019 GWAS ADHD dataset) and ADHD2022 (38,691 cases and 275,986 controls from the 2022 GWAS ADHD dataset). Through the examination of genome-wide association signals, we identified shared genetic variances between circulating immune cells and ADHD, employing the comprehensive ADHD2022 dataset. We primarily utilized inverse variance weighted (IVW) and weighted median methods in our Mendelian randomization research and sensitivity assessments to evaluate diversity and pleiotropy.ResultsAfter adjusting for false discovery rate (FDR), three distinct immunophenotypes were identified as associated with the risk of ADHD: CD33 in Im MDSC (OR=1.03, CI: 1.01~1.04, P=3.04×10−5, PFDR=0.015), CD8br NKT %T cell (OR=1.08, 95%CI: 1.04~1.12, P=9.33×10−5, PFDR=0.023), and CD8br NKT %lymphocyte (OR=1.08, 95%CI: 1.03~1.12, P=3.59×10−4, PFDR=0.066). Furthermore, ADHD showed no statistical effects on immunophenotypes. It’s worth noting that 20 phenotypes exist where ADHD’s appearance could diminish 85% of immune cells, including FSC-A in myeloid DC (β= -0.278, 95% CI: 0.616~0.931, P=0.008), CD3 in CD45RA- CD4+ (β= -0.233, 95% CI: 0.654~0.960, P=0.017), CD62L- monocyte AC (β=0.227, 95% CI: 0.038~1.518, P=0.019), CD33 in CD33br HLA DR+ CD14dim (β= -0.331, 95% CI: 0.543~0.950, P=0.020), and CD25 in CD39+ resting Treg (β=0.226, 95% CI: 1.522, P=0.022), and FSC-A in monocytes (β= -0.255, 95% CI: 0.621~0.967, P=0.234), among others.ConclusionStudies indicate that the immune system’s response influences the emergence of ADHD. The findings greatly improve our understanding of the interplay between immune responses and ADHD risk, aiding in the development of treatment strategies from an immunological perspective.
Clinical and genetic characteristics of BAP1-mutated non-uveal and uveal melanoma
Authors: Matull Johanna , Placke Jan-Malte , Lodde Georg , Zaremba Anne , Utikal Jochen , Terheyden Patrick , Pföhler Claudia , Herbst Rudolf , Kreuter Alexander , Welzel Julia , Kretz Julia , Möller Inga , Sucker Antje , Paschen Annette , Livingstone Elisabeth , Zimmer Lisa , Hadaschik Eva , Ugurel Selma , Schadendorf Dirk , Thielmann Carl Maximilian , Griewank Klaus Georg 
Published: June 2024

BackgroundScreening for gene mutations has become routine clinical practice across numerous tumor entities, including melanoma. BAP1 gene mutations have been identified in various tumor types and acknowledged as a critical event in metastatic uveal melanoma, but their role in non-uveal melanoma remains inadequately characterized.MethodsA retrospective analysis of all melanomas sequenced in our department from 2014–2022 (n=2650) was conducted to identify BAP1 mutated samples. Assessment of clinical and genetic characteristics was performed as well as correlations with treatment outcome.ResultsBAP1 mutations were identified in 129 cases and distributed across the entire gene without any apparent hot spots. Inactivating BAP1 mutations were more prevalent in uveal (55%) compared to non-uveal (17%) melanomas. Non-uveal BAP1 mutated melanomas frequently exhibited UV-signature mutations and had a significantly higher mutation load than uveal melanomas. GNAQ and GNA11 mutations were common in uveal melanomas, while MAP-Kinase mutations were frequent in non-uveal melanomas with NF1, BRAF V600 and NRAS Q61 mutations occurring in decreasing frequency, consistent with a strong UV association. Survival outcomes did not differ among non-uveal melanoma patients based on whether they received targeted or immune checkpoint therapy, or if their tumors harbored inactivating BAP1 mutations.ConclusionIn contrast to uveal melanomas, where BAP1 mutations serve as a significant prognostic indicator of an unfavorable outcome, BAP1 mutations in non-uveal melanomas are primarily considered passenger mutations and do not appear to be relevant from a prognostic or therapeutic perspective.
Can government subsidy promote the light-blue fishery upgrade to deep-blue fishery?
Authors: Zheng Shan , Zhang Ying 
Published: June 2024

IntroductionThe expansion of fishery development from offshore to deep-sea areas has become essential for countries to address environmental constraints and ensure food security. This study aims to establish a cooperative development model for deep-blue fishery involving the government, fishery enterprises, and consumers.MethodsWe constructed an evolutionary game and simulation model to analyze the government's deep-blue fishery subsidy strategy. The model considers the interactions between the government, fishery enterprises, and consumers, evaluating how different subsidy strategies influence the development of deep-blue fishery.ResultsOur results demonstrate that government subsidies can stimulate the growth of deep-blue fishery from both the demand and supply sides. Specifically, the likelihood of government subsidies positively affects fishery enterprises' engagement in deep-blue fishery development and consumers' willingness to purchase deep-blue fishery products. The evolutionary game system reaches different steady states based on the cost-benefit changes for the government, fishery enterprises, and consumers, leading to various optimal subsidy strategies.DiscussionThe findings indicate that the amount of government subsidy should be optimized rather than maximized, as excessive subsidies may not yield proportionate benefits. Additionally, subsidizing fishery enterprises proves to be more effective in promoting the development of deep-blue fishery compared to subsidizing consumers. These insights can guide policymakers in designing efficient subsidy strategies to foster sustainable deep-sea fishery development.
Elucidating the multifaceted roles of GPR146 in non-specific orbital inflammation: a concerted analytical approach through the prisms of bioinformatics and machine learning
Authors: Wu Zixuan , Li Ling , Xu Tingting , Hu Yi , Peng Xin , Zhang Zheyuan , Yao Xiaolei , Peng Qinghua 
Published: June 2024

BackgroundNon-specific Orbital Inflammation (NSOI) is a chronic idiopathic condition marked by extensive polymorphic lymphoid infiltration in the orbital area. The integration of metabolic and immune pathways suggests potential therapeutic roles for C-peptide and G protein-coupled receptor 146 (GPR146) in diabetes and its sequelae. However, the specific mechanisms through which GPR146 modulates immune responses remain poorly understood. Furthermore, the utility of GPR146 as a diagnostic or prognostic marker for NSOI has not been conclusively demonstrated.MethodsWe adopted a comprehensive analytical strategy, merging differentially expressed genes (DEGs) from the Gene Expression Omnibus (GEO) datasets GSE58331 and GSE105149 with immune-related genes from the ImmPort database. Our methodology combined LASSO regression and support vector machine-recursive feature elimination (SVM-RFE) for feature selection, followed by Gene Set Enrichment Analysis (GSEA) and Gene Set Variation Analysis (GSVA) to explore gene sets co-expressed with GPR146, identifying a significant enrichment in immune-related pathways. The tumor microenvironment’s immune composition was quantified using the CIBERSORT algorithm and the ESTIMATE method, which confirmed a positive correlation between GPR146 expression and immune cell infiltration. Validation of GPR146 expression was performed using the GSE58331 dataset.ResultsAnalysis identified 113 DEGs associated with GPR146, with a significant subset showing distinct expression patterns. Using LASSO and SVM-RFE, we pinpointed 15 key hub genes. Functionally, these genes and GPR146 were predominantly linked to receptor ligand activity, immune receptor activity, and cytokine-mediated signaling. Specific immune cells, such as memory B cells, M2 macrophages, resting mast cells, monocytes, activated NK cells, plasma cells, and CD8+ T cells, were positively associated with GPR146 expression. In contrast, M0 macrophages, naive B cells, M1 macrophages, activated mast cells, activated memory CD4+ T cells, naive CD4+ T cells, and gamma delta T cells showed inverse correlations. Notably, our findings underscore the potential diagnostic relevance of GPR146 in distinguishing NSOI.ConclusionOur study elucidates the immunological signatures associated with GPR146 in the context of NSOI, highlighting its prognostic and diagnostic potential. These insights pave the way for GPR146 to be a novel biomarker for monitoring the progression of NSOI, providing a foundation for future therapeutic strategies targeting immune-metabolic pathways.
Prediction of prolonged length of stay on the intensive care unit in severely injured patients—a registry-based multivariable analysis
Authors: Lefering Rolf , Waydhas Christian ,   TraumaRegister DGU
Published: June 2024

PurposeMortality is the primary outcome measure in severely injured trauma victims. However, quality indicators for survivors are rare. We aimed to develop and validate an outcome measure based on length of stay on the intensive care unit (ICU).MethodsThe TraumaRegister DGU of the German Trauma Society (DGU) was used to identify 108,178 surviving patients with serious injuries who required treatment on ICU (2014–2018). In a first step, need for prolonged ICU stay, defined as 8 or more days, was predicted. In a second step, length of stay was estimated in patients with a prolonged stay. Data from the same trauma registry (2019–2022, n = 72,062) were used to validate the models derived with logistic and linear regression analysis.ResultsThe mean age was 50 years, 70% were males, and the average Injury Severity Score was 16.2 points. Average/median length of stay on ICU was 6.3/2 days, where 78% were discharged from ICU within the first 7 days. Prediction of need for a prolonged ICU stay revealed 15 predictors among which injury severity (worst Abbreviated Injury Scale severity level), need for intubation, and pre-trauma condition were the most important ones. The area under the receiver operating characteristic curve was 0.903 (95% confidence interval 0.900–0.905). Length of stay prediction in those with a prolonged ICU stay identified the need for ventilation and the number of injuries as the most important factors. Pearson’s correlation of observed and predicted length of stay was 0.613. Validation results were satisfactory for both estimates.ConclusionLength of stay on ICU is a suitable outcome measure in surviving patients after severe trauma if adjusted for severity. The risk of needing prolonged ICU care could be calculated in all patients, and observed vs. predicted rates could be used in quality assessment similar to mortality prediction. Length of stay prediction in those who require a prolonged stay is feasible and allows for further benchmarking.
Clinical characteristics and the risk factors for the exacerbation of symptoms in patients with inflammatory bowel disease during the COVID-19 pandemic
Authors: Wu Juan , Fang Yuanyuan , Bai Bingqing , Wu Yumei , Liu Qiuyuan , Hu Jing , Hu Naizhong , Mei Qiao , Han Wei 
Published: June 2024

BackgroundIn 2023, the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) Omicron variant caused a large-scale outbreak of coronavirus disease 2019 (COVID-19) in China. It is not clear the risk factors that lead to the exacerbation of symptoms in patients with inflammatory bowel disease (IBD) after COVID-19 infection. Our study aims to find out the risk factors for the exacerbation of IBD-related symptoms in IBD patients with COVID-19 infection and to provide guidance for the clinical management of IBD.MethodsThis is a retrospective, observational study. The online questionnaire was distributed to conduct a survey to collect demographic, clinical, and IBD related characteristics in IBD patients. Univariate and multivariate regression analyses were conducted to assess the independent effects.ResultsIn total, 534 cases of IBD patients were analyzed in our study. Among them, 466 (87.3%) cases diagnosed with COVID-19, 160 (34.3%) cases experienced exacerbation of IBD symptoms, and 84 (18.0%) patients opted for medication discontinuation. Male sex (OR 2.04, 95% CI 1.34–3.49, p = 0.001), and the decrease in body mass index (BMI) (OR 0.93, 95% CI 0.87–1.00, p = 0.035) were positively correlated with the exacerbation of IBD symptoms. Furthermore, the medication discontinuation (OR 2.60, 95% CI 1.58–4.30, p &lt; 0.001) was strongly positively correlated with the exacerbation of IBD symptoms. No significant association was seen between age, comorbidities, smoking, disease activity, vaccination, therapy for COVID-19 and the worsening of IBD symptoms.ConclusionThis study confirms that the infection rate of COVID-19 in China IBD patients was comparable to the general population. Male sex, the decrease in BMI and medication discontinuation are significant risk factors for the exacerbation of IBD-related symptoms in IBD patients with COVID-19 infection.
Research status and hotspots of social frailty in older adults: a bibliometric analysis from 2003 to 2022
Authors: Wang Hengxu , Chen Xi , Zheng MingXiang , Wu Ying , Liu Lihua 
Published: June 2024

BackgroundSocial Frailty is a significant public health concern affecting the elderly, particularly with the global population aging rapidly. Older adults with social frailty are at significantly higher risk of adverse outcomes such as disability, cognitive impairment, depression, and even death. In recent years, there have been more and more studies on social frailty, but no bibliometrics has been used to analyze and understand the general situation in this field. Therefore, by using CiteSpace, VOSviewer, and Bilioshiny software programs, this study aims to analyze the general situation of the research on social frailties of the older adults and determine the research trends and hot spots.MethodsA bibliometric analysis was conducted by searching relevant literature on the social frailty of the older adults from 2003 to 2022 in the Web of Science core database, using visualization software to map publication volume, country and author cooperation networks, keyword co-occurrences, and word emergence.ResultsWe analyzed 415 articles from 2003 to 2022. Brazil has the highest number of articles in the field of social frailty of the older adults, and the United States has the highest number of cooperative publications. Andrew MK, from Canada, is the most published and co-cited author, with primary research interests in geriatric assessment, epidemiology, and public health. “Social Vulnerability,” “Health,” “Frailty,” “Mortality,” and “Older Adult” are among the research hotspots in this field. “Dementia,” “Alzheimer’s disease,” “Population,” and “Covid-19” are emerging research trends in social frailty among the older adults.ConclusionThis scientometric study maps the research hotspots and trends for the past 20 years in social frailty among the older adults. Our findings will enable researchers to better understand trends in this field and find suitable directions and partners for future research.