bluuebunny/crossref_metadata_2025_split huggingface dataset:
Triglyceride-glucose index as a mediator of body mass index and cardiovascular disease in middle-aged and older Chinese adults: a nationally representative longitudinal cohort study
Authors: Gan Ying-Yuan , Zhai Lu , Liao Qian , Huo Rong-Rui 
Published: December 2024

BackgroundBody mass index (BMI) consistently correlates with the triglyceride-glucose (TyG) index, a marker of insulin resistance, which in turn is linked to heightened cardiovascular disease (CVD) risk. Thus, insulin resistance could potentially mediate the association between BMI and CVD risk. However, few studies have explored this mechanism in the general population.MethodsWe used data from the China Health and Retirement Longitudinal Study, which is an ongoing prospective cohort study. It initially enrolled 7233 middle-aged and older Chinese adults who were free of heart disease and stroke at baseline. The exposure variable was BMI. Incident CVD, defined as self-reported physician-diagnosed heart disease and stroke combined, served as the main outcome.ResultsOf the 7 233 participants (mean [SD] age, 58.93 [9.33] years), 3 415 (47.2%) were men. During the 7 years of follow-up, 1 411 incident CVD cases were identified. Both BMI and TyG index were associated with CVD risk (HR per 1-SD increase: BMI, 1.23; 95% CI, 1.17–1.29; TyG, 1.13; 95% CI, 1.07–1.19). The 4-way decomposition analysis show that, overweight increased CVD risk by 28% (HR [total association], 1.28; 95% CI, 1.14–1.45), with 18.1% (95% CI, 2.2%–34.0%) mediated by TyG index (HR [pure indirect association], 1.05; 95% CI, 1.02–1.09); while obesity increased CVD risk by 91% (HR [total association], 1.91; 95% CI, 1.63–2.23), with 9.5% (95% CI, 2.2%–16.7%) mediated by TyG index (HR [pure indirect association], 1.09; 95% CI, 1.03–1.15). No evidence suggested TyG index modified BMI’s association with incident CVD.ConclusionsThe study revealed that the TyG index was associated to CVD risk and acted as a small partial mediator in the relationship between BMI and CVD among middle-aged and older Chinese adults. Consequently, solely addressing insulin resistance might not significantly mitigate the impact of body weight on CVD. Thus, exploring alternative pathways and potential mediators of CVD risk becomes imperative.
Prevalence and risk factors for type 2 diabetes mellitus in women with gestational diabetes mellitus: a systematic review and meta-analysis
Authors: Chen Kaiqi , Tang Lichao , Wang Xinwei , Li Yunhua , Zhang Xijian , Cui Shikui , Chen Wei , Jin Zhao , Zhu Danping 
Published: December 2024

IntroductionThis study aims to explore the risk factors in the progression of gestational diabetes mellitus (GDM) to type 2 diabetes mellitus (T2DM).Material and methodsRelevant studies were comprehensively searched from PubMed, Web of Science, Cochrane Library, and Embase up to March 12. Data extraction was performed. Differences in risk factors were presented as odds ratios (OR) and corresponding 95% confidence intervals (CI). The quality of the included studies was assessed through the Newcastle-Ottawa Scale and the Agency for Healthcare Research and Quality scale.ResultsThis meta-analysis encompassed 46 studies involving a total of 196,494 patients. The factors most strongly associated with the risk of developing T2DM following GDM were the use of progestin-only contraceptives (odds ratio [OR]: 2.12, 95% confidence interval [CI] = 1.00–4.45, P = 0.049), recurrence of GDM (OR: 2.63, 95% CI = 1.88–3.69, P &lt; 0.001), insulin use during pregnancy (OR: 4.35, 95% CI = 3.17–5.96, P &lt; 0.001), pre-pregnancy body mass index (BMI) (OR: 2.97, 95% CI = 2.16–4.07, P &lt; 0.001), BMI after delivery (OR: 4.17, 95% CI = 2.58–6.74, P &lt; 0.001), macrosomia (OR: 3.30, 95% CI = 1.45–7.49, P = 0.04), hypertension (OR: 5.19, 95% CI = 1.31–20.51, P = 0.019), and HbA1c levels (OR: 3.32, 95% CI = 1.81–6.11, P &lt; 0.001). Additionally, age (OR: 1.71, 95% CI = 1.23–2.38, P = 0.001), family history of diabetes (OR: 1.47, 95% CI = 1.27–1.70, P &lt; 0.001), BMI during pregnancy (OR: 1.06, 95% CI = 1.00–1.12, P = 0.056), fasting blood glucose (FBG) (OR: 1.58, 95% CI = 1.36–1.84, P &lt; 0.001), 1-hour oral glucose tolerance test (OGTT) (OR: 1.38, 95% CI = 1.02–1.87, P = 0.037), and 2-hour OGTT (OR: 1.54, 95% CI = 1.28–1.58, P &lt; 0.001) were identified as moderate-risk factors for the development of T2DM.ConclusionThe systematic review and meta-analysis identified several moderate- to high-risk factors associated with the progression of T2DM in individuals with a history of GDM. These risk factors include the use of progestin-only contraceptives, pre-pregnancy BMI, BMI after delivery, macrosomia, hypertension, persistently elevated levels of HbA1c, fasting blood glucose (FBG), 1-hour and 2-hour oral glucose tolerance tests (OGTT), age, and family history of diabetes. Our findings serve as evidence for the early prevention and clinical intervention of the progression from GDM to T2DM and offer valuable insights to guide healthcare professionals in formulating customized management and treatment strategies for female patients with diverse forms of GDM.Systematic review registrationhttps://www.crd.york.ac.uk/PROSPERO/, identifier CRD42024545200.
Case Report and literature review: Delayed diagnosis of ARCL1B due to a newly reported homozygous mutation c.464A>C p. (Tyr155Ser) in the EFEMP2 gene
Authors: Ouyang Lixue , Yang Fan , Duan Hongyu , Wang Chuan 
Published: December 2024

BackgroundAutosomal recessive cutis laxa type 1B (ARCL1B) is an extremely rare disease characterized by severe systemic connective tissue abnormalities, including cutis laxa, aneurysm and fragility of blood vessels, birth fractures and emphysema. The severity of this disease ranges from perinatal death to manifestations compatible with survival. To date, no cases have been reported in the Chinese population. Due to its rarity, the disease is susceptible to misdiagnosis or missed diagnosis by clinicians. By presenting this case and reviewing the relevant literature, the aim is to enhance clinicians’ awareness and vigilance in diagnosing this disease.Case presentationWe report a 7-month-old Chinese male infant who initially presented with severe respiratory infection, respiratory failure, and heart failure, and was misdiagnosed with Takayasu arteritis. Despite treatment, his condition did not improve. Due to the features of vascular malformations, developmental delay, and early onset of the disease, whole exome sequencing (WES) was performed, results revealed a homozygous mutation c.464A&gt;C in exon 5 on the EFEMP2 gene p. (Tyr155Ser) that had never been reported before. Molecular protein prediction results suggest that this mutation site exhibits a high probability of pathogenicity. Combining the clinical manifestations, the results of cardiac color ultrasound and cardiac great vessels angiography, and the WES results, the patient was finally diagnosed with ARCL1B. Given the absence of established guidelines for the clinical manifestation, treatment, follow-up, and prognosis of ARCL1B, we searched the literatures of pubmed and web of science from inception to February 2024 to provide an essential reference for physicians to deepen the understanding of ARCL1B.ConclusionThe EFEMP2 gene mutation identified in this patient has not been previously reported, expanding the mutation spectrum of the gene. This is the first documented case of this disease in the Chinese population. The diagnostic and therapeutic journey of this patient, along with the accompanying literature review, provides valuable insights. It highlights the importance of clinicians maintaining a high level of vigilance when encountering cases involving younger patients with multiple pulmonary artery aneurysms, as they may indicate the presence of this rare disease.
Characterization of a novel AEL allele harboring a c.28 + 5G>A mutation on the ABO*A2.01 background: a study utilizing PacBio third-generation sequencing and functional assays
Authors: Shao Lin-Nan , Song Wen-Qian , Zhou Lu , Pan Ling-Zi , Duan Ying , Xiao Nan , Zhou Shi-Hang , Liang Xiao-Hua 
Published: December 2024

BackgroundMutations in the ABO gene, including base insertions, deletions, substitutions, and splicing errors, can result in blood group subgroups associated with the quantity and quality of blood group antigens. Here, we employed third-generation PacBio sequencing to uncover a novel AEL allele arising from an intron splice site mutation, which altered the expected A2 phenotype to manifest as an Ael phenotype. The study aimed to characterize the molecular mechanism underlying this phenotypic switchMethodsA 53-year-old healthy male blood donor with an atypical agglutination pattern was investigated. PacBio sequencing was used to sequence the entire ABO gene of the proband. In silico analysis predicted aberrant splicing, which was experimentally verified using a minigene splicing assay.ResultsBased on serological characteristics, the proband was determined to have an Ael phenotype. Sequencing revealed heterozygosity for ABO*O.01.02 and a novel ABO*A2.01-like allele with an additional c.28 + 5G&gt;A mutation in intron 1. In silico predictions also indicated that this mutation is likely to cause aberrant splicing. Minigene analysis suggested that this mutation disrupted the 5’-end canonical donor splice site in intron 1, activated a cryptic donor site, and resulted in a 167 bp insertion, producing a truncated glycosyltransferase (p.Lys11Glufs*66). Meanwhile, a small amount of the wild type transcript was also generated through normal splicing, contributing to the Ael phenotype.ConclusionA novel AEL allele was identified in a Chinese male blood donor on the ABO*A2.01 background, characterized by the c.28 + 5G&gt;A variant. This study provides insights into the molecular basis of blood group antigen variation.
Geny: a genotyping tool for allelic decomposition of killer cell immunoglobulin-like receptor genes
Authors: Zhou Qinghui , Ghezelji Mazyar , Hari Ananth , Ford Michael K. B. , Holley Connor , Sahinalp S. Cenk , Numanagić Ibrahim 
Published: December 2024

IntroductionAccurate genotyping of Killer cell Immunoglobulin-like Receptor (KIR) genes plays a pivotal role in enhancing our understanding of innate immune responses, disease correlations, and the advancement of personalized medicine. However, due to the high variability of the KIR region and high level of sequence similarity among different KIR genes, the generic genotyping workflows are unable to accurately infer copy numbers and complete genotypes of individual KIR genes from next-generation sequencing data. Thus, specialized genotyping tools are needed to genotype this complex region.MethodsHere, we introduce Geny, a new computational tool for precise genotyping of KIR genes. Geny utilizes available KIR allele databases and proposes a novel combination of expectation-maximization filtering schemes and integer linear programming-based combinatorial optimization models to resolve ambiguous reads, provide accurate copy number estimation, and estimate the correct allele of each copy of genes within the KIR region. Results &amp; DiscussionWe evaluated Geny on a large set of simulated short-read datasets covering the known validated KIR region assemblies and a set of Illumina short-read samples sequenced from 40 validated samples from the Human Pangenome Reference Consortium collection and showed that it outperforms the existing state-of-the-art KIR genotyping tools in terms of accuracy, precision, and recall. We envision Geny becoming a valuable resource for understanding immune system response and consequently advancing the field of patient-centric medicine.
Immune-related thyroid dysfunction as a positive prognostic factor for patients with lung cancer in China: a real-world retrospective study
Authors: Guo Ge , Jing Zihan , Dou Wenrui , Wang Guiqin , Dang JunJie , Li Yajie , Wang Ruqiong , Zhang Huan , Sun Jing , Shang Lihua 
Published: December 2024

IntroductionThe relationship between immune-related thyroid dysfunction (irTD) and survival rates in cancer patients remains unclear. Furthermore, the impact of variations in immunotherapy line numbers and pathological types among lung cancer patients on this relationship has not been fully elucidated. This study aims to evaluate the potential of irTD as a prognostic marker for immunotherapy in Chinese patients with lung cancer.MethodsA retrospective analysis was conducted on data collected from patients with locally advanced or metastatic lung cancer who received immune checkpoint inhibitor treatment at the Harbin Medical University Cancer Hospital. The study period spanned from December 1, 2016, to November 30, 2023. The primary endpoints were progression-free survival (PFS) and overall survival (OS), while the objective response rate served as the secondary endpoint.ResultsAmong the 361 patients in this study, 42.7% developed irTD. Significant differences were observed between the groups with and without irTD regarding inflammatory indices, thyroid-stimulating hormone levels, and thyroid autoantibody positivity (P &lt; 0.05). Patients with irTD demonstrated longer OS (32.5 vs. 22 months, HR: 0.65, 95% CI: 0.49-0.88; P = 0.005). For NSCLC patients, OS was significantly prolonged in those with irTD (40.8 vs. 27.2 months, HR: 0.68, 95% CI: 0.48-0.96; P = 0.028). Similarly, SCLC patients who developed irTD exhibited longer OS (27.9 vs. 13.8 months, HR: 0.51, 95% CI: 0.29-0.90; P = 0.022). Notably, irTD was observed exclusively in patients receiving immunotherapy in the second or later lines, showing a significant association with extended OS (40.8 vs. 19.4 months, HR: 0.56, 95% CI: 0.35-0.88; P = 0.012), while the presence of irTD during first-line immunotherapy did not confer a benefit to patients (32.4 vs 24.5 months, HR: 0.74, 95% CI: 0.50-1.10; P = 0.134). The effects of different irTD types, severities, or clinical symptoms on PFS and OS did not differ significantly (P &gt; 0.05).ConclusionirTD demonstrates potential as a predictive marker for long-term survival benefits in Chinese patients with lung cancer. However, our exploratory analysis indicates that this association was exclusively observed in individuals receiving immunotherapy as a second-line or subsequent treatment.
Immunogenicity of the CoronaVac vaccine in children: a real-world study
Authors: Aguilar-Jimenez Wbeimar , Rodriguez-Perea Ana Lucia , Chvatal-Medina Mateo , Velilla Paula A. , Zapata-Builes Wildeman , Monsalve-Escudero Laura M. , Zapata-Cardona Maria I. , Tabares-Guevara Jorge Humberto , Rincón Daniel S. , Hernandez Juan C. , Tabares Yulied , Lopez-Carvajal Liliana , Rugeles Maria T. 
Published: December 2024

BackgroundDespite its proven effectiveness and safety, there are limited real-world data on CoronaVac’s immunogenicity in children, especially in lower-income countries, particularly for SARS-CoV-2 variants. We present a real-world study evaluating CoronaVac’s immunogenicity in Colombian children stratified by previous exposure to this virus.Methods89 children aged 3-11 years were enrolled (50 Non-Exposed and 39 Exposed). Saliva samples were collected every 15 days to monitor potential SARS-CoV-2 infection, and blood samples were taken at two and six months after vaccination, to evaluate immunogenicity. Total IgG and IgA antibodies were measured by ELISA, and neutralizing titers against B.1, Delta, Mu, and Omicron variants were assessed by plaque reduction assay. T-cells were stimulated with wild-type and Omicron peptide pools to analyze activation-induced markers, memory phenotype, cytotoxic molecules, and cytokine production by flow cytometry.FindingsCoronaVac was well tolerated, with only 7.8% infection incidence in both Exposed and Non-Exposed groups. It elicits a robust humoral response through IgG, IgA, and neutralizing antibodies against all variants. Despite waning, most participants maintained neutralizing titers ≥20 over time. CoronaVac also induced a polyfunctional cellular response against various strains, albeit reduced against Omicron, regardless of prior exposure. This response, characterized by IFN-γ/TNF-α and cytotoxic molecule production, was more pronounced in CD4+ than in CD8+ T-cells and remained detectable even after 6 months.InterpretationCoronaVac induces robust humoral and cellular immune responses against various variants in children, suggesting cross-recognition. However, these responses diminish over time, particularly in the context of variants, indicating the need for booster doses.
HLA-E/Mtb specific CD4+ and CD8+ T cells have a memory phenotype in individuals with TB infection
Authors: Voogd Linda , Riou Catherine , Scriba Thomas J. , van Wolfswinkel Marjolein , van Meijgaarden Krista E. , Franken Kees L. M. C. , Wilkinson Robert J. , Ottenhoff Tom H. M. , Joosten Simone A. 
Published: December 2024

IntroductionTuberculosis (TB) is the deadliest infectious disease worldwide and novel vaccines are urgently needed. HLA-E is a virtually monomorphic antigen presentation molecule and is not downregulated upon HIV co-infection. HLA-E restricted Mtb specific CD8+ T cells are present in the circulation of individuals with active TB (aTB) and Mtb infection (TBI) with or without HIV co-infection, making HLA-E restricted T cells interesting vaccination targets for TB.MethodsHere, we performed in-depth phenotyping of HLA-E/Mtb specific and total T cell populations in individuals with TBI and in individuals with aTB or TBI and HIV using HLA-E/Mtb tetramers.Results and DiscussionWe show that HIV co-infection is the main driver in changing the memory distribution of HLA-E/Mtb specific CD4+ and CD8+ T cell subsets. HLA-E/Mtb specific CD4+ and CD8+ T cells were found to circulate with comparable frequencies in all individuals and displayed expression of KLRG1, PD-1 and 2B4 similar to that of total T cells. The presence of HLA-E/Mtb specific T cells in individuals with aTB and TBI highlights the potential of HLA-E as a vaccine target for TB.
Association between somatic microsatellite instability, hypermutation status, and specific T cell subsets in colorectal cancer tumors
Authors: Thomas Claire E. , Takashima Yasutoshi , Wesselink Evertine , Ugai Tomotaka , Steinfelder Robert S. , Buchanan Daniel D. , Qu Conghui , Hsu Li , Dias Costa Andressa , Gallinger Steven , Grant Robert C. , Huyghe Jeroen R. , Thomas Sushma S. , Ogino Shuji , Phipps Amanda I. , Nowak Jonathan A. , Peters Ulrike 
Published: December 2024

BackgroundMicrosatellite instability-high (MSI-high) tumors comprise ~15% of sporadic colorectal cancers (CRC) and are associated with elevated T cell infiltration. However, the universality of this response across T cell subtypes with distinct functions is unknown.MethodsIncluding 1,236 CRC tumors from three observational studies, we conducted in-situ T cell profiling using a customized 9-plex (CD3, CD4, CD8, CD45RA, CD45RO, FOXP3, KRT, MKI67, and DAPI) multispectral immunofluorescence assay. MSI status was assessed through polymerase chain reaction or immunohistochemical assays. We used multivariable ordinal logistic regression to estimate odds ratios (OR per increasing quantile) and 95% confidence intervals (CIs) for the association of MSI status with quantiles of T cell densities in either tumor epithelial or stromal tissue areas.ResultsCompared to microsatellite instability low or microsatellite stable (MSI-low/MSS) tumors, MSI-high status was associated with higher density for the majority of immune subsets (twelve out of eighteen) in both epithelial and stromal tissue areas. The strongest associations were for CD3+CD8+ T cells in epithelial areas [OR (95% CI) for naive, memory, and regulatory subsets = 3.49 (2.57, 4.75); 2.82 (2.10, 3.78); 3.04 (2.24, 4.13), respectively]. Conversely, stromal area CD3+CD4+ memory T cells were inversely associated [OR (95% CI) = 0.68 (0.51, 0.91)].DiscussionMSI-high status was strongly associated with higher densities of most T cell subsets in both epithelial and stromal tissue areas. Our investigation supports efforts to identify patients who may be more likely to respond to current immunotherapy treatments.SignificanceThis study helps us better understand how a clinically relevant tumor phenotype, microsatellite instability status, is related to different functioning T cell densities in colorectal tumors, which may impact future immunotherapy strategies.
New insights into roles of IL-7R gene as a diagnostic biomarker for post-stroke depression
Authors: Liu Mengyu , Sun Haochen , Yao Qun , Wang Duohao , Zhang Jihong , Ye Xing , Qi Xinyang 
Published: December 2024

BackgroundPost-stroke depression (PSD) is the most prevalent neuropsychiatric complication following a stroke. The inflammatory theory suggests that PSD may be associated with an overactive inflammatory response. However, research findings regarding inflammation-related indicators in PSD remain inconsistent and elusive. This study aimed to screen the diagnostic markers that helps to distinguish between PSD and post-stroke non-depressed (PSND) patients.MethodsTwo GEO datasets, including patients with major depression disease (MDD) and controls (CON, GSE98793), ischemic stroke (IS) and CON (GSE16561), were used to analyzed differentially expressed genes (DEGs) and perform enrichment analysis. Protein-protein interaction (PPI) network and Random Forest analysis were used to screen the candidate hub genes. CIBERSORT was performed to analyze the immune infiltration. We analyzed the proteins that interact with the hub genes using string database, circRNA-miRNA-mRNA ceRNA network of the hub genes using RNAInter, miRWalk, miRDB and Starbase databases, and the drugs that regulate the hub genes by DSigDB database. We further verified the expression of the hub genes using Quantitative Real-Time PCR from the blood of patients and CON.ResultsFrom the screened 394 DEGs, the DEGs were found primarily related to activation of immune response. PPI network and random forest analysis obtained the hub genes: IL-7R. ROC analysis showed that IL-7R had a good diagnostic and predictive effect on MDD and IS patients. The proportions of macrophages M0 and monocytes in patients were significantly higher than those in CON. We constructed PPI network and ceRNA network that related to IL-7R. The perturbagen signatures and computational drug signatures were found that can target IL-7R. The expression of IL-7R in MDD, PSND and PSD patients was lower than that in CON, and the expression of IL-7R in PSD patients was lower than that in PSND patients.ConclusionThese findings indicate that IL-7R may serve as a diagnostic marker to distinguish between PSD and PSND patients, and targeting IL-7R as a therapeutic target could potentially improve treatment outcomes for PSD.