bluuebunny/crossref_metadata_2025_split huggingface dataset:
Next-generation sequencing and immuno-informatics for designing a multi-epitope vaccine against HSV-1-induced uveitis
Authors: Cao He , Cao Zhi , Han Yue , Shan Jing 
Published: January 2025

BackgroundUveitis, characterized by intraocular inflammation, poses significant clinical challenges, often leading to vision impairment or blindness. Herpes Simplex Virus type 1 (HSV-1) is a major cause of virus-induced uveitis. This study aims to design a novel multi-epitope vaccine targeting HSV-1 glycoproteins B, C, D, H, and L using an immuno-informatics approach, which are essential for viral entry and pathogenesis.MethodsThe study identified epitopes for CD8+ T cells, CD4+ T cells, and B cells within the target glycoproteins. These epitopes were systematically evaluated for conservancy, immunogenicity, non-allergenicity, non-glycosylated regions, and binding affinities. A multi-epitope construct was designed, incorporating these epitopes along with an adjuvant, a PADRE sequence, and suitable linkers. In-silico immune simulations were performed to evaluate the vaccine’s potential to activate both innate and adaptive immune responses. Molecular docking simulations assessed the binding interactions between the multi-epitope vaccine and Toll-like receptor (TLR-9).ResultsThe selected epitopes demonstrated high conservancy, immunogenicity, and non-allergenicity. The multi-epitope construct effectively activated cytokine production, immunoglobulin secretion, and T cell responses in in-silico immune simulations. Molecular docking simulations showed strong binding interactions between the vaccine and TLR-9, suggesting enhanced antigen presentation capabilities.ConclusionThis comprehensive immuno-informatics approach provides a precision immunotherapy strategy for uveitis by leveraging computational modeling and predictive analytics to design a multi-epitope vaccine for HSV-1. The in-silico results indicate the vaccine’s potential efficacy in activating immune responses. Future experimental validation and clinical studies are necessary to confirm the safety and efficacy of this proposed vaccine in managing uveitis and preserving vision.
Efficacy and safety of PD-1/PD-L1 inhibitors in advanced or recurrent endometrial cancer: a meta-analysis with trial sequential analysis of randomized controlled trials
Authors: Ren Ji , Wang Jinghe , Wang Yanan , Yang Dongying , Sheng Jianming , Zhu Shili , Liu Yunli , Li Xiaoqi , Liu Wei , Zhang Binbin 
Published: January 2025

BackgroundThe combination of programmed cell death 1 (PD-1)/programmed death ligand 1 (PD-L1) inhibitors with chemotherapy (CT) is currently under evaluation as a first-line treatment for advanced or recurrent endometrial cancer (EC). This study sought to assess the efficacy and safety of this therapeutic combination in patients with advanced or recurrent EC.MethodsWe performed an exhaustive review of randomized controlled trials (RCTs) up to September 25, 2024, examining the efficacy and safety of combining PD-1/PD-L1 inhibitors with CT versus CT alone (or plus placebo) in advanced or recurrent EC. Efficacy was measured by progression-free survival (PFS) and overall survival (OS), while safety was assessed by the incidence of any grade or grade ≥ 3 adverse events (AEs). We calculated hazard ratios (HRs) for PFS and OS, as well as risk ratios (RRs) for AEs, each accompanied by 95% confidence intervals (CIs). To evaluate heterogeneity, we employed Cochran’s Q test, I2 statistics, and 95% prediction intervals (PIs). Trial sequential analysis (TSA) was conducted using R Version 4.3.1, STATA Version 12.0, and TSA Version 0.9.5.10 Beta software.ResultsOur analysis incorporated 6 studies, encompassing a total of 2,954 patients. The combination of PD-1/PD-L1 inhibitors with CT significantly improved PFS (HR = 0.617, 95% CI: 0.506-0.752; 95% PI: 0.334-1.140) and OS (HR = 0.774, 95% CI: 0.664-0.902; 95% PI: 0.553-1.083) compared to CT alone (or plus placebo) in the overall population. Subgroup analysis based on mismatch repair (MMR) status revealed pronounced benefits in PFS and OS for patients with deficient MMR (dMMR) (PFS: HR = 0.344, 95% CI: 0.269-0.438; 95% PI: 0.231-0.510; OS: HR = 0.371, 95% CI: 0.245-0.562; 95% PI: 0.025-5.461) compared to those with proficient MMR (pMMR) (PFS: HR = 0.772, 95% CI: 0.627-0.950; 95% PI: 0.394-1.512; OS: HR = 0.996, 95% CI: 0.692-1.435; 95% PI: 0.021-47.662). Although there was no observed difference in the incidence of any grades AEs (RR = 0.994, 95% CI: 0.982-1.006; 95% PI: 0.978-1.009), the risk of grade ≥ 3 AEs was elevated in the group receiving PD-1/PD-L1 inhibitors in combination with CT (RR = 1.132, 95% CI: 1.023-1.252; 95% PI: 0.836-1.532).ConclusionThe combination of PD-1/PD-L1 inhibitors with CT significantly improved PFS and OS in advanced or recurrent EC patients, with particularly pronounced benefits observed in those with dMMR. Clinicians can tailor treatment strategies according to individual patient characteristics to optimize therapeutic outcomes, while remaining alert to the possibility of AEs in clinical practice.Systematic review registrationhttps://www.crd.york.ac.uk/PROSPERO/, identifier CRD42024595455.
Biomarker combinations from different modalities predict early disability accumulation in multiple sclerosis
Authors: Fleischer Vinzenz , Brummer Tobias , Muthuraman Muthuraman , Steffen Falk , Heldt Milena , Protopapa Maria , Schraad Muriel , Gonzalez-Escamilla Gabriel , Groppa Sergiu , Bittner Stefan , Zipp Frauke 
Published: January 2025

ObjectiveEstablishing biomarkers to predict multiple sclerosis (MS) disability accrual has been challenging using a single biomarker approach, likely due to the complex interplay of neuroinflammation and neurodegeneration. Here, we aimed to investigate the prognostic value of single and multimodal biomarker combinations to predict four-year disability progression in patients with MS.MethodsIn total, 111 MS patients were followed up for four years to track disability accumulation based on the Expanded Disability Status Scale (EDSS). Three clinically relevant modalities (MRI, OCT and blood serum) served as sources of potential predictors for disease worsening. Two key measures from each modality were determined and related to subsequent disability progression: lesion volume (LV), gray matter volume (GMV), retinal nerve fiber layer, ganglion cell-inner plexiform layer, serum neurofilament light chain (sNfL) and serum glial fibrillary acidic protein. First, receiver operator characteristic (ROC) analyses were performed to identify the discriminative power of individual biomarkers and their combinations. Second, we applied structural equation modeling (SEM) to the single biomarkers in order to determine their causal inter-relationships.ResultsBaseline GMV on its own allowed identification of subsequent EDSS progression based on ROC analysis. All other individual baseline biomarkers were unable to discriminate between progressive and non-progressive patients on their own. When comparing all possible biomarker combinations, the tripartite combination of MRI, OCT and blood biomarkers achieved the highest discriminative accuracy. Finally, predictive causal modeling identified that LV mediates significant parts of the effect of GMV and sNfL on disability progression.ConclusionMultimodal biomarkers, i.e. different major surrogates for pathology derived from MRI, OCT and blood, inform about different parts of the disease pathology leading to clinical progression.
Stemness-related gene signatures as a predictive tool for breast cancer radiosensitivity
Authors: Lai Jinzhi , Huang Rongfu , Huang Jingshan 
Published: January 2025

BackgroundUnderstanding the role of cancer stemness in predicting breast cancer (BRCA) response to radiotherapy is crucial for optimizing treatment outcomes. This study developed a stemness-based signature to identify BRCA patients who are likely to benefit from radiotherapy.MethodsGene expression data for BRCA patients were obtained from the TCGA and METABRIC databases, including 920 TCGA-BRCA and 1980 METABRIC-BRCA patients. Univariate and multivariate Cox regression analyses were used to construct a radiosensitivity signature. Immune cell infiltration and pathway enrichment analyses were conducted using ESTIMATE and GSVA methods. The TIDE algorithm and the pRRophetic platform were employed to predict responses to radiotherapy. Radioresistant BRCA cells were examined using a colony formation assay. Key genes identified in the radiosensitivity signature were validated in vitro by qRT-PCR.ResultsBy analyzing gene expression data from 920 BRCA samples, we identified a set of 267 stemness-related genes between high and low mRNAsi groups. Based on these genes, a radiosensitivity signature comprising two stemness-related genes (EMILIN1 and CYP4Z1) was constructed, stratifying patients into radiosensitive (RS) and radioresistant (RR) groups. Radiotherapy within the RS group significantly improved prognosis compared to non-radiotherapy patients. This signature was further validated in the METABRIC dataset. Notably, patients in the RS group also exhibited a significantly better response to immunotherapy compared to the RR group. We established a radioresistant BRCA cell line using the MCF-7 breast cancer cell line. A radioresistant breast cancer cell line (MCF-7/IR) was established by progressive exposure to increasing radiation doses. Comparative clonogenic and CCK8 assays demonstrated a radioresistant phenotype in the MCF-7/IR compared to MCF-7. In vitro studies utilizing both the MCF-7/IR and MCF-7 cell lines validated the expression of two radiosensitivity genes.ConclusionThis study identified a stemness-related gene signature predictive of radiosensitivity in breast cancer. This signature may guide personalized treatment strategies and inform the development of novel radiosensitizing agents.
Hepatic encephalopathy and spontaneous bacterial peritonitis are associated with increased liver-related readmissions in cirrhosis
Authors: Wang Shan , Zhang Lin , Li Jin , Feng Jiajun , Gao Jie , Huang Rui 
Published: January 2025

IntroductionLiver disease remains a significant global health concern. In China, the number of patients with liver cirrhosis is estimated to reach 7 million. In addition to the high risk of death, cirrhosis leads to several severe complications. Patients with cirrhosis have significantly longer hospital stays and higher total hospital costs than those without cirrhosis. We aimed to investigate the predictors of readmission among patients with cirrhosis in China.Materials and methodsWe conducted a retrospective study to evaluate adult patients with cirrhosis. Data on various sociodemographic, clinical, and hospitalization characteristics were collected. We defined the primary endpoint as the first liver-related readmission occurring within 30–90 days of initial hospitalization. Adult patients with cirrhosis admitted to our hospital between January 2009 and December 2022 were included. Differences between groups were analyzed using Student’s t-test and chi-square test. Logistic and multiple linear regression analyses were performed to identify predictors associated with readmission and the length of the first hospitalization.ResultsIn total, 1,285 patients were diagnosed with cirrhosis. Among these patients, 767 (59.7%) were males, and the mean age was 58.9 ± 12.3 years. Seventy-two (5.6%) and 154 (12.0%) patients were readmitted within 30 and 90 days, respectively. Compared with those who were not readmitted, patients readmitted at 30-day and 90-day had a higher proportion of males, ascites, spontaneous bacterial peritonitis, electrolyte abnormalities, higher Child-Pugh–Turcotte scores, longer initial hospital stays, and higher initial hospitalization costs. Logistic regression analysis indicated that hepatic encephalopathy, spontaneous bacterial peritonitis, diabetes, and ascites were predictors of 30- and 90-day readmission. Hypertension and spontaneous bacterial peritonitis were significant predictors of the length of the first hospitalization.ConclusionPatients with cirrhosis presenting with hepatic encephalopathy, ascites, and spontaneous bacterial peritonitis may have a higher risk of rehospitalization.
Improved jet lag recovery is associated with a weaker molecular biological clock response around the time of expected activity onset
Authors: Boutrin Marie-Claire , Richardson Melissa E. S. , Oriola Feyikemi , Bolo Samira 
Published: January 2025

IntroductionProperly timed environmental light input to the suprachiasmatic nucleus (SCN) in the brain is crucial in maintaining the 24-hour biological rhythm (circadian rhythm). However, light exposure at the wrong time of the day-night cycle is disruptive to circadian-regulated behaviors such as the sleep-wake cycle and memory. While factors such as jet lag, variations in day length, and light at night are known disruptors to the timing of activity onset following rest, the molecular consequence of the intersection of multiple disruptions is less understood.MethodsHere, we expose mice to a jet lag paradigm under two light-dark (LD) conditions (12:12 LD and 8:16 LD) coupled with additional light exposure at night during the recovery period (known as negative masking), previously demonstrated to improve jet lag-related memory loss in mice.ResultsOur results show that jet lag exposure in both LD cycles (to a greater extent in 8:16 LD) increased the fold-change of circadian gene expression in the SCN relative to the dark onset. The further addition of light during the jet lag recovery period reduced typical changes in circadian gene expression in the SCN to minimal levels under both LD cycles.DiscussionThis study uncovers a novel explanation for the impact of multiple disruptive light exposures on gene expression of the molecular SCN clock in the brain.
Successful treatment of generalized myasthenia gravis with telitacicept: a Chinese case series and literature review
Authors: Song Xiaodong , He Yang , Jiang Hong , Yu Yao , Sun Yue , Zhang Zhaoxu 
Published: January 2025

BackgroundDespite existing treatments of generalized myasthenia gravis (gMG), there remains a need for more effective therapies with fewer side effects. Telitacicept, targeting B lymphocyte stimulator (BLyS) and a proliferation-inducing ligand (APRIL), emerges as a potential novel therapy for gMG.Case presentationIn our study, four patients with gMG to standard treatments underwent an 8-week course of telitacicept monotherapy. Post-treatment, all patients exhibited satisfactory improvements. The Myasthenia Gravis Foundation of America Quantitative Myasthenia Gravis (MGFA-QMG) scores, 15-item Myasthenia Gravis Quality of Life (MGQOL-15) scores, and MG-associated Activities of Daily Living (MG-ADL) scores showed a marked reduction, indicating decreased disease severity and enhanced quality of life. Additionally, immunological assessments revealed a decrease in CD19+B lymphocyte counts and acetylcholine receptor (AChR) antibodies. Only one patient reported a mild, transient injection reaction.ConclusionFavorable clinical improvement and mild adverse events for gMG in treated with telitacicept were observed. However, larger-scale and longer-term studies are necessary to confirm these results and fully establish the role of telitacicept in the treatment of gMG.
Linear association between high-sensitivity C-reactive protein and postoperative delirium after general anesthesia: a cross-sectional study
Authors: Qin Xiao , Ren Junming , Xing Chunping , Chen Lijiao , Wang Renjie , Tian Shouyuan 
Published: January 2025

ObjectiveTo investigate the association between high-sensitivity C-reactive protein (Hs-CRP) levels and the risk of postoperative delirium (POD) following general anesthesia.MethodsThis retrospective cross-sectional study included 644 patients who underwent general anesthesia. Univariate and multivariate logistic regression analyses were performed to evaluate the relationship between Hs-CRP and POD, with subgroup analyses used to assess stratified associations. Receiver operator characteristic (ROC) curve analysis was employed to assess the predictive efficacy of Hs-CRP for POD. Restricted cubic spline (RCS) analysis was conducted to explore the linear relationship between the log-transformed Hs-CRP (Log10Hs-CRP) and POD risk.ResultsThe total population consisted of 644 individuals with a mean age of 64.02 ± 13.20 years, 506 (78.60%) of whom were male, and 114 patients (17.7%) had POD. Compared to the lower Hs-CRP group, patients in the higher Hs-CRP group exhibited higher age, heart rate, white blood cell count, blood urea nitrogen, creatinine, uric acid, fasting glucose, hemoglobin A1c, fibrinogen, D-dimer, and a higher prevalence of CKD, but lower hemoglobin, high-density lipoprotein cholesterol, albumin and estimated glomerular filtration rate. Additionally, the prevalence of POD was higher in the higher Hs-CRP group (24.7% vs. 9.5%, p &lt; 0.001). Multivariate logistic regression confirmed that elevated Hs-CRP and its forms (Log10Hs-CRP, standardized Hs-CRP, and higher Hs-CRP group) consistently increased the risk of POD across all adjusted models (p &lt; 0.05). Stratified analyses further highlighted significant associations between Hs-CRP and POD in specific subgroups, notably in patients aged ≥65 years, female patients, and those with or without hypertension, diabetes, or stroke history, and without chronic kidney disease (p &lt; 0.05). ROC curve analysis demonstrated that Hs-CRP had a significant predictive ability for POD in the overall population (AUC = 0.646), as well as in male (AUC = 0.644) and female patients (AUC = 0.654). Additionally, RCS analysis indicated a linear positive association between Log10Hs-CRP and POD risk (p = 0.003, nonlinear p = 0.896).ConclusionElevated Hs-CRP levels are significantly associated with an increased risk of POD following general anesthesia.
Development and validation of a food and nutrition literacy questionnaire for Chinese parents of children with functional constipation (FNLQ-p)
Authors: Yang Jie , Wang Hui , Shen Yanchi , Yang Hui , Huang Yan , Cao Jinjin 
Published: January 2025

ObjectivesChildhood functional constipation is a widespread condition with a global prevalence. Dietary interventions play a crucial role in the management of childhood constipation. Hence, the development and validation of a specialized food and nutrition literacy assessment tool for parents of school-aged children with functional constipation is of paramount significance.MethodsOn the basis of literature review, the first draft was formed, and the results of expert correspondence and pre survey were combined to delete and modify the first draft. In the second stage, 459 parents of school-age children with constipation were invited to fill out the questionnaire. Item analysis, exploratory factor analysis, and confirmatory factor analysis were then conducted to assess the questionnaire's reliability and validity.ResultsThe final scale comprises 4 dimensions and 25 items. Exploratory factor analysis extracted four common factors (nutrition knowledge, nutrition skills, nutrition interaction, nutrition evaluation), and the cumulative variance contribution rate was 64. 532%. The content validity index (I-CVI) of each item level is 0.86–1, the content validity index (S-CVI) at the scale level is 0.96. The overall Cronbach'sα coefficient was 0.85. Confirmatory factor analysis supported the four-factor structure derived from exploratory analysis, with all relevant fit indices meeting standard criteria.ConclusionsThe food and nutrition literacy questionnaire developed in our study had good validity and reliability, making it a useful tool for assessing the food and nutrition literacy among parents of school-aged children diagnosed with functional constipation.
Risk factors for pelvic lymph node metastasis in cervical cancer: a retrospective analysis of 186 patients
Authors: Sun Xingyu , He Lijuan , Wang Shaohua 
Published: January 2025

BackgroundPelvic lymph node metastasis is a critical factor influencing prognosis and treatment strategies in cervical cancer patients. This study aimed to identify significant clinical and pathological risk factors associated with pelvic lymph node metastasis in patients with cervical cancer.MethodsWe conducted a retrospective analysis of 186 cervical cancer patients treated at the Affiliated Hospital, Southwest Medical University from January 2010 to December 2020. Patients were divided into two groups: those with pelvic lymph node metastasis (n=40) and those without (n=146). Data on demographics, clinical characteristics, pathological features, and treatment modalities were collected. Statistical analysis included t-tests, chi-square tests, and logistic regression to evaluate potential risk factors for lymph node metastasis.ResultsPatients with pelvic lymph node metastasis were significantly older (mean age 52.5 ± 8.3 years) than those without metastasis (mean age 48.7 ± 10.2 years; p=0.023). High-risk HPV positivity was significantly associated with lymph node metastasis (75% vs. 41%, p=0.001). Lymphovascular invasion was observed in 75% of the metastatic group compared to 24.7% in the non-metastatic group (p&lt;0.001). Tumor size &gt;4 cm was more frequent in patients with metastasis (50% vs. 12.3%, p&lt;0.001). Multivariate logistic regression analysis identified high-risk HPV infection (OR 4.13, 95% CI: 2.09-8.17, p&lt;0.001), lymphovascular invasion (OR 7.87, 95% CI: 4.05-15.29, p&lt;0.001), and tumor size &gt;4 cm (OR 6.24, 95% CI: 3.24-12.02, p&lt;0.001) as independent risk factors for pelvic lymph node metastasis.ConclusionThis study identifies several independent risk factors for pelvic lymph node metastasis in cervical cancer, including high-risk HPV infection, lymphovascular invasion, and tumor size greater than 4 cm. These findings can help guide clinical decision-making and individualized treatment planning, improving outcomes for patients with cervical cancer. Further prospective studies are warranted to validate these findings.