bluuebunny/crossref_metadata_2025_split huggingface dataset:
The effect of HLA genotype on disease onset and severity in CTLA-4 insufficiency
Authors: Posadas-Cantera Sara , Mitsuiki Noriko , Emmerich Florian , Patiño Virginia , Lorenz Hanns-Martin , Neth Olaf , Dybedal Ingunn , Taskén Kjetil , Schäffer Alejandro A. , Grimbacher Bodo , Gámez-Díaz Laura 
Published: January 2025

IntroductionHuman Cytotoxic-T-lymphocyte-antigen-4 (CTLA-4) insufficiency caused by heterozygous germline mutations in CTLA4 is a complex immune dysregulation and immunodeficiency syndrome presenting with reduced penetrance and variable disease expressivity, suggesting the presence of disease modifiers that trigger the disease onset and severity. Various genetic and non-genetic potential triggers have been analyzed in CTLA-4 insufficiency cohorts, however, none of them have revealed a clear association to the disease. Multiple HLA haplotypes have been positively or negatively associated with various autoimmune diseases and inborn errors of immunity (IEI) due to the relevance of MHC in the strength of the T cell responses.MethodsIn this exploratory study, we investigated the association of disease onset, severity and clinical manifestations of CTLA-4 insufficiency with specific HLA class I (A, B and C) and class II (DRB1 and DQB1) alleles in forty-three individuals harboring heterozygous mutations in CTLA4. Twenty-six out of the 43 recruited individuals presented moderate or severe clinical symptoms whereas 17 were completely healthy. HLA frequency analysis, odds ratio analysis and genetic linkage analysis were used.ResultsThe principal statistical analyses showed no positive association between the HLA genotypes analyzed with the disease onset or the disease severity. We found potential risk associations of HLA-DQB1*05:01 and HLA-DRB1*01:02 with respiratory tract involvement and HLA-C*05:01 with affection of the neurological system in the CTLA-4-insufficient patients. Additionally, we found a potential protective association of HLA-DRB1*01:01 with gastrointestinal symptoms.DiscussionEven though, our findings suggest that HLA-A, -B, -C, DRB1, and DQB1 do not contribute to the onset or severity of disease in CTLA-4 insufficiency, certain HLA-alleles may influence the manifestation of specific symptoms. We advocate for further investigation of specific class I and class II HLA alleles as potential disease modifiers in larger clinical cohorts of CTLA-4 insufficiency.
Single-cell mitophagy patterns within the tumor microenvironment modulate intercellular communication, impacting the progression and prognosis of hepatocellular carcinoma
Authors: Li Zhengyan , Chen Wei , Yao Shu , Peng Zuxiang , Liu Hongming , Tang Yongliang , Feng Yi 
Published: January 2025

BackgroundHepatocellular carcinoma (HCC) is a common malignant tumor of the digestive system with a high incidence that seriously threatens patients’ lives and health. However, with the rise and application of new treatments, such as immunotherapy, there are still some restrictions in the treatment and diagnosis of HCC, and the therapeutic effects on patients are not ideal.MethodsTwo single-cell RNA sequencing (scRNA-seq) datasets from HCC patients, encompassing 25,189 cells, were analyzed in the study. We utilized non-negative matrix factorization (NMF) clustering to identify mitophagy patterns in HCC TME cells, including cancer-associated fibroblasts (CAFs), T cells, B cells, and tumor-associated macrophages (TAMs). Cell-to-cell communication was analyzed using the CellChat package, and pseudotime trajectory analysis was performed using the Monocle package. Gene regulatory networks were investigated with the SCENIC package, and survival analyses were conducted with mitophagy-related signatures.ResultsHCC samples analysis identified 22 clusters, including 7 principal cell types. Complex cell communications were observed among these cell types. Mitophagy-related CAFs, TAMs, CD8+ T cells, and B cells were identified. These subtypes had different biological states, cell-cell communications, and metabolic pathways. Mitophagy levels were elevated in tumor samples. Changes in mitophagy-related genes within specific cell subtypes were associated with different overall survival rates. However, mitophagy did not seem to affect the effectiveness of immunotherapy.ConclusionThis study provides evidence that mitophagy within the HCC TME modulates intercellular communication, influencing tumor progression and patient prognosis. Targeting mitophagy may offer a promising approach to improve the long-term prognosis of HCC patients.
Exploring post-rehabilitation plasticity with intra-cerebral recordings on anomic profiles
Authors: Trébuchon Agnès , Fasola Alexia , Sabadell Véronique , Dubarry Anne-Sophie , Carron Romain , Bartolomei Fabrice , Alario F.-Xavier 
Published: January 2025

BackgroundPatients with drug-resistant epilepsy involving the language network often exhibit anomic profiles in daily life due to difficulties with lexical selection processes. Very little evidence is available regarding the effects of language rehabilitation in this population.Objective(s)We aim to induce brain plasticity combined with improvements in behavioral performance using language therapy in patients with epilepsy.MethodsWe implemented a therapy focused on phonological and semantic features of infrequent words over three treatment sessions, each targeting a specific semantic category. Intracranial signals were recorded in 10 patients during baseline and post-therapy picture-naming sessions. Response times and the percentages of correct responses during naming tests were collected. Time-frequency analyses were conducted on intracranial signals, and comparisons were made between baseline and post-therapy conditions for each patient.ResultsHalf of the patients demonstrated improved naming skills following the treatment. We observed significantly different recruitment of frontotemporal areas in the left hemisphere (including Broca's area) post-therapy in patients that improved naming skills. Specifically, we found significantly different high-gamma activity in the posterior left inferior frontal gyrus 500 ms after stimulus onset in patients with improved naming skills vs. non-improved naming skills. This effect was not observed in the right hemisphere.ConclusionsThese findings suggest that enhanced performance following language therapy is associated with modifications in posterior left IFG activations during latencies closely tied to the lexical selection process.
The association between the neutrophil-to-lymphocyte ratio, platelet-to-lymphocyte ratio, and lymphocyte-to-monocyte ratio and delirium in ischemic stroke patients
Authors: Wang Pangbo , Huang Jing , Xu Liwei , Hu Rong 
Published: January 2025

BackgroundDelirium is a severe neuropsychiatric symptom following acute ischemic stroke (IS) and is associated with poor outcomes. Systemic inflammation and immune dysregulation are believed to contribute to the pathophysiology of delirium. The neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), and lymphocyte-to-monocyte ratio (LMR) are widely recognized as convenient and reliable biomarkers of systemic inflammation. However, their association with delirium after IS remains unclear.MethodsIn this study, we identified IS patients requiring ICU admission from the Medical Information Mart for Intensive Care (MIMIC)-IV database. We employed multivariable logistic regression and restricted cubic splines (RCS) to assess the association between the NLR, PLR, and LMR and delirium. Two-sample Mendelian randomization (MR) analysis was performed to further explore their causal relationship at the genetic level.ResultsA total of 1,436 patients with IS were included in this study, of whom 214 (14.9%) had delirium. In the multivariate logistic regression analysis, after adjustment for confounders, the patients in the highest quartile of the NLR (odds ratio [OR] 2.080, 95% confidence interval [CI], 1.282–3.375) and LMR (OR 0.503, 95% CI 0.317–0.798) and the patients in the second quartile of the PLR (OR 1.574, 95% CI 1.019–2.431) were significantly associated with delirium. The RCS function showed a progressive increase in the risk of delirium with higher NLR and PLR and lower LMR. In the MR analysis, only the PLR was negatively associated with the risk of delirium.ConclusionThe observational studies found significant associations between the NLR, PLR, and LMR and delirium. However, the MR analysis only demonstrated a potential protective causal relationship between the PLR and delirium. Further prospective studies are needed to validate their association and to elucidate the underlying mechanisms.
Evaluation of the diagnostic efficiency of fluorescence in situ hybridization for pulmonary tuberculosis: a systematic review and meta-analysis
Authors: Hu Yu-Qi , Liu Kang , Lai Le-Qing , He Yi-Ru , Hong Li-Ping , Jiang Chu-Qian , Liu Si-Min , Cao Ming-Zhu 
Published: January 2025

ObjectiveIn clinical practice, an accurate and efficient detection approach for pulmonary tuberculosis (PTB) is highly needed. The fluorescence in situ hybridization (FISH) assay for PTB might be a suitable alternative to current tests. However, a systematic assessment of the diagnostic performance of this new approach is not available. Our study aimed to determine the diagnostic accuracy of FISH for PTB.MethodsWe examined PubMed and three more databases including Embase, Cochrane Library, and Web of Science databases from their establishment to November 10, 2023, for published articles on the diagnostic performance of FISH on individuals with clinical suspicion of tuberculosis (TB). QUADAS-2 was used to evaluate the literature’s quality. We used Meta-DiSc software to create forest plots.ResultsThe search yielded 7 studies, involving 1,224 sputum samples that could be included in our meta-analysis. The combined FISH sensitivity and specificity were 0.89 (95% CI 0.86–0.92) and 0.98 (95% CI 0.97–0.99), respectively. Furthermore, subgroup analysis was performed based on probes and PTB incidence.ConclusionFISH may be useful in the diagnosis of pulmonary tuberculosis. The sensitivity and specificity of FISH are high for most sputum specimens. Additionally, FISH has better diagnostic performance in countries with low PTB prevalence than in high PTB prevalence countries. We hope this study will find a new and effective tool for the early diagnosis of PTB.
Individualized treatment recommendations for patients with locally advanced head and neck squamous cell carcinoma utilizing deep learning
Authors: Zhang Linmei , Zhu Enzhao , Shi Jiaying , Wu Xiao , Cao Shaokang , Huang Sining , Ai Zisheng , Su Jiansheng 
Published: January 2025

BackgroundThe conventional treatment for locally advanced head and neck squamous cell carcinoma (LA-HNSCC) is surgery; however, the efficacy of definitive chemoradiotherapy (CRT) remains controversial.ObjectiveThis study aimed to evaluate the ability of deep learning (DL) models to identify patients with LA-HNSCC who can achieve organ preservation through definitive CRT and provide individualized adjuvant treatment recommendations for patients who are better suited for surgery.MethodsFive models were developed for treatment recommendations. Their performance was assessed by comparing the difference in overall survival rates between patients whose actual treatments aligned with the model recommendations and those whose treatments did not. Inverse probability treatment weighting (IPTW) was employed to reduce bias. The effect of the characteristics on treatment plan selection was quantified through causal inference.ResultsA total of 7,376 patients with LA-HNSCC were enrolled. Balanced Individual Treatment Effect for Survival data (BITES) demonstrated superior performance in both the CRT recommendation (IPTW-adjusted hazard ratio (HR): 0.84, 95% confidence interval (CI), 0.72–0.98) and the adjuvant therapy recommendation (IPTW-adjusted HR: 0.77, 95% CI, 0.61–0.85), outperforming other models and the National Comprehensive Cancer Network guidelines (IPTW-adjusted HR: 0.87, 95% CI, 0.73–0.96).ConclusionBITES can identify the most suitable treatment option for an individual patient from the three most common treatment options. DL models facilitate the establishment of a valid and reliable treatment recommendation system supported by quantitative evidence.
Case report: Electrical impedance tomography-guided ventilator weaning in an obese patient with severe pneumonia
Authors: Liu Yuxia , Liu Rui , Li Bin , Cai Libi , Hou Jieqi , Zhao Wei 
Published: January 2025

BackgroundElectrical impedance tomography (EIT) evaluates lung function by providing continuous, real-time monitoring of regional lung ventilation distribution to guide the restoration of lung ventilation. Patients with obesity who are dependent on mechanical ventilation often struggle with weaning. This case report highlights the potential of EIT to guide the weaning of ventilator-dependent patients in an obese patient with severe pneumonia.Case summaryA 23-year-old male obese patient was admitted to Zhongshan People’s Hospital in November 2023 due to progressive dyspnea. He suffered from recurrent fever and worsening oxygenation and had a 20+ year history of syringomyelia. Combined with abnormal computed tomography imaging, the discovery of a viral infection in the bronchoalveolar lavage fluid, and next-generation sequencing results, he was diagnosed with severe pneumonia. In addition to conventional treatment, EIT was used to guide him through postural changes and ventilation recovery. EIT-informed prone positioning improved ventilation distribution and facilitated successful ventilator weaning on day 26. The patient was discharged after recovering spontaneous respiratory function.ConclusionEIT may help ventilator-dependent obese patients achieve tailored targets to improve ventilatory outcomes.
Evaluating factors that impact scoring an open response situational judgment test: a mixed methods approach
Authors: Iqbal Muhammad Zafar , Ivan Rodica , Robb Colleen , Derby Jillian 
Published: January 2025

IntroductionSituational judgment tests (SJT) are commonly used in admissions to measure skills associated with professionalism. Although open-response SJTs have shown strong psychometric properties, assessors’ personal beliefs, experiences, and cultural backgrounds may influence how they perceive, organize and evaluate information within test takers’ diverse responses. Additionally, SJT research typically focuses on reliability and predictive validity, whereas the construct validity of open response SJTs remains underexplored. This mixed methods study aims to address this gap by exploring the construct-(ir)relevant factors that may impact assessors’ evaluation of professionalism in open response SJTs.MethodsFor this study, we used data from Casper, an open response SJT commonly used in professional program admissions. In Study I, a quantitative content analysis was conducted on 160 responses to identify factors which were significant predictors of low and high scores. Correlation coefficients and logistic regression models were used to evaluate the relationship between each factor and response scores. In Study II, think-aloud activities were conducted with 23 Casper assessors to directly observe how they evaluated responses. All interviews were transcribed verbatim, which were then thematically analyzed using an inductive coding technique.ResultsResults from both the content analyses and think-aloud activities revealed that several construct relevant factors influenced scores. Scores were impacted by the extent to which test takers demonstrated the competencies probed for by the SJT, engaged with the context of the presented ethical dilemma, provided in-depth justifications for their response, considered various perspectives relevant to the presented dilemma, and provided creative solutions or insightful arguments for the suggested approach. Mixed results were found with respect to construct irrelevant factors, such as the flow, cohesion, and kinds of phrases used in the response.ConclusionThis mixed methods study contributes to the construct validity of SJTs by investigating construct relevant and irrelevant factors that may impact assessors’ evaluation of open responses. The findings of this study provide evidence that open-response SJTs are valid approaches to measure professional competencies more broadly, both in terms of what test takers focus on in their responses, as well as in terms of how they construct their responses.
Composition and the predicted functions of fungal communities and the key drivers in acidic soils of Jiaodong Peninsula, China
Authors: Liu Jing , Wazir Zafran Gul , Hou Guoqin , Wang Guizhen , Rong Fangxu , Xu Yuzhi , Liu Kai , Li Mingyue , Liu Aiju , Liu Hongliang , Sun Hongwen 
Published: January 2025

IntroductionSoil acidification imperils soil health and hinders the agricultural sustainability. As being more tolerant than bacteria to soil acidification, so it would be more meaningful for agricultural management and crop yield to characterize fungal community in acidic soils and manifest its key drivers.MethodThis study investigated the composition and diversity of fungal communities and its key driving factors by collecting 90 soil samples from the acidic region of Jiaodong Peninsula China, spanning 3 × 104 km2.ResultsThe results indicated that most soil pH values ranged from 5.01 to 6.42, and the exchangeable acidity (EA) content raised significantly (p &lt; 0.01) along with soil acidic degree increasing. However, no significant differences were found in fungal community diversity and composition among various soil samples, which were all predominantly habited with the phyla of Ascomycota and Basidiomycota. Results of the linear discriminant analysis effect size (LEfSe) analysis revealed that saprophytic fungi were biomarkers of the slightly acidic soil (pH 6.0–6.5), including Nectriaceae, Thielavia, Nectria, Haematonectria, and unclassified Microascaceae, while plant pathogenic fungi, such as Didymellaceae, were biomarkers of the soils pH &lt; 5.5. Similarly, the FUNGuild results also indicated that saprophytic fungi and pathogenic fungi were the dominant functional guilds in the investigated acidic soils, accounting for 66% of the total fungal communities. Redundancy analysis (RDA) revealed that soil pH as well as nitrate nitrogen (NO3−-N) and total nitrogen (TN) significantly associated with fungal community at the phylum level, whilst soil pH was the only factor significantly linked to individual fungal classes (p &lt; 0.01 or 0.05). The further Mantel test analysis and structural equation modeling (SEM) suggested that, in contrast to the negative and directive driving of soil pH on fungal communities' variation, the specific plant pathogenic fungi, Gibberella and Didymellaceae, were significantly and positively associated with soil acidic characteristics (p &lt; 0.05).DiscussionThese findings highlighted that, in addition to modulating the variation of soil fungal community, soil acidification might prime some plant pathogens development. So that, more attentions should be focused on impact of soil acidification on fungal ecology, as well as plant pathogenic fungi.
High prevalence of fecal carriage of extended-spectrum beta-lactamase producing Enterobacterales among patients with urinary tract infections in rural Tanzania
Authors: Macha Magreth Erick , Qi Weihong , Seiffert Salome N. , Bösch Anja , Kohler Philipp , Urassa Honorathy Msami , Haller Sabine , West Erin , Rohacek Maja Weisser , Babouee Flury Baharak 
Published: January 2025

IntroductionThe global rise of extended-spectrum beta-lactamase-producing Enterobacterales (ESBL-PE) challenges resource-limited countries with insufficient laboratory infrastructure. This study investigates fecal carriage and risk factors for ESBL-PE and carbapenemase-producing organisms among patients with urinary tract infection (UTI) in rural Tanzania.MethodsThis cross-sectional study was conducted at St. Francis Regional Referral Hospital, Ifakara, Tanzania, from October 2021 to August 2023, involving 326 UTI patients. Demographic data and resistance risk factors were collected via structured questionnaires. Stool samples collected pre-antibiotic treatment were screened for ESBL-PE and carbapenemase locally. Positive samples underwent further analysis in Switzerland using MALDI-ToF, Vitek MS, and whole-genome sequencing. Multivariable analysis assessed predictors associated with ESBL-PE carriage for risk factors with p &lt; 0.05.ResultsWe enrolled 326 UTI patients (median age: 35.5 years, range: 25–52) and 189 (58.0%) were females. Fecal ESBL-PE colonization was detected in 70.9% of patients, predominantly E. coli (62.8%) and K. pneumoniae (33.0%). Whole-genome sequencing identified diverse phylogroups and sequence types, with CTX-M-15 being the most common ESBL gene. IncF plasmids were the primary carriers. Younger age (aOR: 0.98, 95% CI: 0.97–0.99; p = 0.0239) and inpatient status (aOR: 1.77, 95% CI: 1.08–2.91; p = 0.0036) were significant risk factors for ESBL-PE carriage.ConclusionThe high prevalence of ESBL-PE fecal carriage in rural Tanzania highlights the need for improved infection control and further research into community transmission dynamics.
Exploring the causal role of plasma metabolites and metabolite ratios in prostate cancer: a two-sample Mendelian randomization study
Authors: Feng Changzhou , Li Haining , Zhang Chu , Zhou Ying , Zhang Huanhuan , Zheng Ping , Zhao Shaolin , Wang Lei , Yang Jin 
Published: January 2025

BackgroundProstate cancer (PCa), the most prevalent malignant neoplasm in males, involves complex biological mechanisms and risk factors, many of which remain unidentified. By employing a novel two-sample Mendelian randomization (MR) approach, this study aims to elucidate the causal relationships between the circulating metabolome and PCa risk, utilizing comprehensive data on genetically determined plasma metabolites and metabolite ratios.MethodsFor the MR analysis, we utilized data from the GWAS Catalog database to analyze 1,091 plasma metabolites and 309 ratios in relation to PCa outcomes within two independent GWAS datasets. The inverse variance weighted (IVW) method was the primary approach for determining the existence of the causal relationship, supplemented by additional MR methods for heterogeneity, pleiotropy, and cross-validation. The false discovery rate (FDR) and Bonferroni correction were applied to identify the most significant causative associations. Additionally, reverse MR and Steiger filtering were conducted to ascertain whether PCa influenced the observed metabolite levels. Furthermore, metabolic pathway analysis was conducted with MetaboAnalyst 6.0 software.ResultsIn the MR analysis, our findings reveal three overlapped metabolite ratios (arginine to glutamate, phosphate to uridine, and glycerol to mannitol/sorbitol) inversely associated with PCa risk. Following FDR correction (FDR &lt; 0.05), cysteinylglycine disulfide was identified as a potential reducer of PCa risk, whereas Uridine and N-acetyl-L-glutamine (NAG) were pinpointed as potential risk factors. Notably, NAG (OR 1.044; 95% CI 1.025–1.063) emerged as a metabolite with significant causal influence, as confirmed by stringent Bonferroni correction (P &lt; 0.05/1400). Steiger’s directionality test (P &lt; 0.001) and reverse MR confirmed the proposed causal direction. Furthermore, metabolic pathway analysis revealed a significant association between the “Glutathione Metabolism” pathway and PCa development.ConclusionThis study provides novel insights into the potential causal effects of plasma metabolites and metabolite ratios on PCa. The identified metabolites and ratios could serve as candidate biomarkers, contributing to the elucidation of PCa’s biological mechanisms.