bluuebunny/crossref_metadata_2025_split huggingface dataset:
Association between the hemoglobin A1c/High-density lipoprotein cholesterol ratio and stroke incidence: a prospective nationwide cohort study in China
Authors: Huang Chaojuan , You Hongtao , Zhang Yuyang , Fan Ligang , Feng Xingliang , Shao Naiyuan 
Published: January 2025

Abstract

Background
Stroke has emerged as an escalating public health challenge among middle-aged and older individuals in China, closely linked to glycolipid metabolic abnormalities. The Hemoglobin A1c/High-Density Lipoprotein Cholesterol (HbA1c/HDL-C) ratio, an integrated marker of glycolipid homeostasis, may serve as a novel predictor of stroke risk.

Methods
Our investigation utilized data from the China Health and Retirement Longitudinal Study cohort (2011–2018). Stroke cases were identified based on self-reported, physician-confirmed diagnoses. Logistic regression models were established to determine the correlation between HbA1c/HDL-C and stroke prevalence (2011) as well as between cumulative mean HbA1c/HDL-C (2011–2015) and new stroke incidence (2015–2018). Additionally, smoothed curve fitting, subgroup analyses, and interaction tests were conducted to ensure the robustness of the findings.

Results
In the cross-sectional analysis, 8,502 participants were enrolled, of whom 189 had a history of stroke. Our findings revealed a significant positive linear relationship between HbA1c/HDL-C and stroke prevalence after adjusting for covariates (OR: 1.26, 95% CI: 1.09–1.45). When HbA1c/HDL-C was categorized into tertiles, only the highest tertile (T3) showed a significant correlation with stroke prevalence compared to the lowest tertile (T1) (OR:1.71, 95% CI: 1.05–2.77). In the longitudinal analysis of 5,165 participants, 336 cases of new-onset stroke were identified over a follow-up period of 7 years. Adjusting for confounders, individuals with higher cumulative mean HbA1c/HDL-C exhibited an increased likelihood of new stroke incidence (OR: 1.14, 95% CI: 1.01–1.29). Using the T1 of cumulative mean HbA1c/HDL-C as a reference, the fully adjusted OR for stroke was 1.65 (95% CI: 1.21–2.24) in T2 and 1.54 (95% CI: 1.08–2.19) in T3. The predictive value of the HbA1c/HDL-C in stroke risk assessment have been significantly improved compared to the traditional HDL-C and HbA1c. Consistent associations were observed across most stratified subgroups.

Conclusions
Elevated baseline and cumulative mean HbA1c/HDL-C levels are significantly associated with an increased risk of stroke among middle-aged and older individuals in China, underscoring the potential of HbA1c/HDL-C as a clinical marker for long-term stroke risk assessment and prevention strategies.
Association between triglyceride glucose index and adverse cardiovascular prognosis in patients with atrial fibrillation without diabetes: a retrospective cohort study
Authors: Gong Aobo , Cao Ying , Li Zexi , Li Wentao , Li Fanghui , Tong Yao , Hu Xianjin , Zeng Rui 
Published: January 2025

Abstract

Background
Atrial fibrillation (AF) is the most prevalent arrhythmia encountered in clinical practice. Triglyceride glucose index (Tyg), a convenient evaluation variable for insulin resistance, has shown associations with adverse cardiovascular outcomes. However, studies on the Tyg index’s predictive value for adverse prognosis in patients with AF without diabetes are lacking.

Methods
This retrospective study utilized electronic medical records to collect data on patients with AF hospitalized at West China Hospital from January to June 2020. Participants were categorized into three groups based on their Tyg index levels. The primary outcome, major adverse cardiovascular events, included cardiac death, stroke, and myocardial infarction. Kaplan–Meier curve, Cox proportional hazards regression model, and restricted cubic spline were employed to explore the relationship between the Tyg index and outcomes. The predictive performance of the CHA2DS2-VASc model was evaluated after incorporating the Tyg index.

Results
The study comprised 864 participants (mean age 67.69 years, 55.32% male, 57.52% paroxysmal AF). Patients with high Tyg index had a significantly higher risk of developing major adverse cardiovascular events (MACE) (P < 0.001, hazard ratio: 2.05, 95% confidence interval:1.65–2.56). The MACE risk in the middle Tyg group was similar to that in the low Tyg group (P = 0.1) during the 48-month follow-up period. However, focusing on the last 24 months revealed a higher MACE risk (P = 0.015) in the middle Tyg group. The restricted cubic spline analysis revealed an S-shaped correlation between Tyg and MACE. The CHA2DS2-VASc model combined with the Tyg index showed improved predictive performance and net benefit.

Conclusions
A high Tyg index is associated with poorer prognosis in patients with AF without diabetes. Integrating the Tyg index into the CHA2DS2-VASc model may enhance its predictive performance, offering clinical utility.
Multiple gene-deletion vaccinia virus Tiantan strain against mpox
Authors: Zhu Yilong , Li Dapeng , Zhao Renshuang , Chen Minghua , Li Yue , Yang Xia , Mao Hongyue , Li Xiao , Li Yiquan , Shang Chao , Xia Xianzhu 
Published: January 2025

Abstract
Monkeypox virus (MPXV) is an important zoonotic pathogenic virus, which poses serious threats to public health. MPXV infection can be prevented by immunization against the variola virus. Because of the safety risks and side effects of vaccination with live vaccinia virus (VACV) strain Tian Tan (VTT), we constructed two gene-deleted VTT recombinants (TTVAC7 and TTVC5). The immunogenicity and protective effects of the gene-deleted VTT vaccine were assessed using BALB/C mice challenged with VTT and New Zealand rabbits challenged with MPXV. The results demonstrated strong humoral and cellular immune responses. The VTT-specific and neutralizing antibody titers, specific T cell levels, and degree of dendritic cell maturation of the mice, in addition to the MPXV neutralizing antibody titers and IFN-γ, IL-6, and TNF-α levels of the rabbits were markedly higher in the groups immunized with TTVAC7 and TTVC5 than the control groups (p < 0.05). Moreover, immunization with TTVAC7 and TTVC5 reduced morbidities caused by VACV and MPXV infection. The weight change, lung histological score, and residual virus of the mouse model (p < 0.05). Similarly, the temperature change, pock number, lung histological score, and residual virus of the rabbit model were significantly reduced in the groups immunized with TTVAC7 and TTVC5 (p < 0.05). Collectively, these results demonstrate that TTVAC7 and TTVC5 may be used as potential live attenuated vaccines against MPXV infection.
LLT1 overexpression renders allogeneic-NK resistance and facilitates the generation of enhanced universal CAR-T cells
Authors: Zhu Shuxian , Zuo Shiyu , Li Chuo , You Xingjie , Jiang Erlie , Feng Xiaoming , Luo Yuechen 
Published: January 2025

Abstract

Background
The benefit of universal CAR-T cells over autologous CAR-T cell therapy is that they are a treatment that is ready to use. However, the prevention of graft-versus-host disease (GVHD) and host-versus-graft reaction (HVGR) remains challenging. Deleting class I of human leukocyte antigen (HLA-I) and class II of human leukocyte antigen (HLA-II) can prevent rejection by allogeneic T cells; however, natural killer (NK) cell rejection due to the loss of self-recognition remains unresolved. This study tested whether the overexpression of Lectin-like transcript 1 (LLT1), an NK cell inhibitory ligand, in T cell receptor (TCR) and HLA-I/II disrupted universal CD38-targeting CAR-T cells could prevent rejection by allogeneic NK cells.

Methods
We generated CD38-targeting universal CAR-T cells by transducing T cells with lentiviruses encoding the CD38 CAR and LLT1 constructs. T cells were subjected to CD38, TCR, HLA-I, and HLA-II gene knockdown using CRISPR/Cas9, followed by lentiviral transduction. We performed cytotoxicity, proliferation, and cytokine assays to evaluate the functionality of universal chimeric antigen receptor-T cell (UCAR-T) cells and conducted in vitro and in vivo assays, including allogeneic responses and RNA sequencing, to assess their resistance to allogeneic T and NK cells, anti-leukemia efficacy, and persistence in treating hematologic malignancies.

Results
Genetic editing of CD38 universal CAR-T cells, including CD38, T cell receptor alpha constant (TRAC), beta-2-microglobulin (B2M), and class II major histocompatibility complex transactivator (CIITA) knockdowns, was successfully achieved. In vitro, LLT1 overexpression boosted CAR-T cell proliferation and antitumor activity, leading to a transcriptional signature characterized by elevated stemness-related markers (SELL, BCL6, TCF7, and CD27) and increased levels of IL-10 and other cytokines. It also effectively mitigates rejection by allogeneic NK and T cells. In a humanized T-cell acute lymphoblastic leukemia (T-ALL) model, CD38 allogeneic universal CAR-T cells demonstrated superior survival rates and tumor clearance with reduced inflammatory responses.

Conclusion
According to these results, LLT1 overexpression enhances UCAR-T cell activity and prevents allogeneic rejection, providing essential insights for the development of universal CAR-T cell therapy.
Binding and cleavage of pro-urokinase by a tegument extract of Fasciola hepatica newly excysted juveniles activate the host fibrinolytic system
Authors: Serrat Judit , Torres-Valle María , De Marco Verissimo Carolina , Siles-Lucas Mar , González-Miguel Javier 
Published: January 2025

Abstract
Plasmin, the final product of fibrinolysis, is a broad-spectrum serine protease that degrades extracellular matrix (ECM) components, a function exploited by multiple pathogens for dissemination purposes. The trematode Fasciola hepatica is the leading cause of fasciolosis, a major disease of livestock and an emerging zoonosis in humans. Infection success depends on the ability of F. hepatica newly excysted juveniles (FhNEJ) to penetrate the host intestinal wall, a process that remains incompletely understood. We have previously shown that FhNEJ are capable of binding plasminogen (PLG), the zymogen of plasmin, on their tegument surface, which leads to plasmin generation in the presence of host-derived PLG activators and subsequent degradation of laminin, a major component of the intestinal ECM. Here, we describe the interaction between a tegument extract of FhNEJ and the precursor of the urokinase-type PLG activator (pro-u-PA). We found that F. hepatica cathepsins B3, L3, enolase and glutathione S-transferase mediate this interaction, suggesting a multifactorial or moonlighting role for these proteins. Additionally, our results revealed that the tegument of FhNEJ contains a protease that is capable of cleaving and activating pro-u-PA into its catalytically active form, which positively impacts the capacity of the parasites to generate plasmin from the host PLG. Collectively, our findings indicate that FhNEJ interact with the host fibrinolytic system at multiple levels, reinforcing the potential of targeting this interaction as a strategy to prevent FhNEJ trans-intestinal migration and infection success.
Impact of mechanical ventilation on severe acute kidney injury in critically ill patients with and without COVID-19 – a multicentre propensity matched analysis
Authors: Perschinka Fabian , Mayerhöfer Timo , Engelbrecht Teresa , Graf Alexandra , Zajic Paul , Metnitz Philipp , Joannidis Michael 
Published: January 2025

Abstract

Background
Acute kidney injury (AKI) is common in critically ill patients and is associated with increased morbidity and mortality. Its complications often require renal replacement therapy (RRT). Invasive mechanical ventilation (IMV) and infections are considered risk factors for the occurrence of AKI. The use of IMV and non-invasive ventilation (NIV) has changed over the course of the pandemic. Concomitant with this change in treatment a reduction in the incidences of AKI and RRT was observed. We aimed to investigate the impact of IMV on RRT initiation by comparing critically ill patients with and without COVID-19. Furthermore, we wanted to investigate the rates and timing of RRT as well as the outcome of patients, who were treated with RRT.

Results
A total of 8,678 patients were included, of which 555 (12.8%) in the COVID-19 and 554 (12.8%) in the control group were treated with RRT. In the first week of ICU stay the COVID-19 patients showed a significantly lower probability for RRT initiation (day 1: p < 0.0001, day 2: p = 0.021). However, after day 7 a reversed HR was found. In mechanically ventilated patients the risk was significantly higher for the initiation of RRT over the entire stay. While in non-COVID-19 patients this was a non-significant trend, in COVID-19 patients the risk for RRT was significantly increased. The median delay between initiation of IMV and requirement of RRT was observed to be longer in COVID-19 patients (5 days [IQR: 2–11] vs. 2 days [IQR: 1–5]). The analysis restricted to patients with RRT showed a significantly higher risk for ICU death in patients requiring IMV compared to patients without IMV.

Conclusion
The analysis demonstrated that IMV as well as COVID-19 are associated with an increased risk for initiation of RRT. The association between IMV and risk of RRT initiation was given for all investigated time intervals. Additionally, COVID-19 patients showed an increased risk for RRT initiation during the entire ICU stay within patients admitted to an ICU due to respiratory disease. In COVID-19 patients treated with RRT, the risk of death was significantly higher compared to non-COVID-19 patients.
Yeast cell wall polysaccharides accelerate yet in-feed antibiotic delays intestinal development and maturation via modulating gut microbiome in chickens
Authors: Guo Fangshen , Qiao Jianing , Hu Zeqiong , Huang Jia , Bi Ruichen , Abbas Waseem , Zhen Wenrui , Guo Yuming , Wang Zhong 
Published: January 2025

Abstract

Background
It is important to promote intestinal development and maturation of chicks for feed digestion and utilization, intestinal health, and disease resistance. This study aimed to investigate the effects of dietary yeast cell wall polysaccharides (YCWP) addition on intestinal development and maturation of chickens and its potential action mechanism.

Methods
180 one-day-old male Arbor Acres broilers were randomly assigned to three groups containing control (basal diets without any antibiotics or anticoccidial drug), bacitracin methylene disalicylate (BMD)-treated group (50 mg/kg) and YCWP-supplemented group (100 mg/kg).

Results
Compared with control group, in-feed antibiotic BMD continuous administration significantly decreased crypt depth (d 21) and villus height (d 42) along with mucosal maltase activity (d 42) in the ileum (P < 0.05). Also, BMD markedly downregulated gene expression levels of β-catenin, lysozyme, occludin and FABP-2 (d 21) and innate immune related genes CD83 and MHC-I mRNA levels (d 42, P < 0.05), and decreased goblet cell counts in the ileum of chickens (d 21 and d 42, P < 0.05). While, TLR-2, TLR-6 and iNOS mRNA abundances were notably upregulated by BMD treatment (d 42, P < 0.05). Nevertheless, dietary YCWP addition significantly increased the ratio of villus height to crypt depth (d 21), villus surface area (d 21 and d 42), ileal alkaline phosphatase and maltase activities as well as goblet cell (d 21 and d 42) and IgA-producing plasma cell numbers as compared to BMD treatment (d 21, P < 0.05). YCWP addition also upregulated gene expression levels of Lgr5, Wnt/β-catenin signaling pathway related gene (Wnt3, β-catenin, d 21; β-catenin, d 42), intestinal cells proliferation marker Ki-67 and barrier function related genes (occludin, d 21 and d 42, P < 0.05). Moreover, YCWP significantly increased antigen presenting cell marker related genes (MHC-II, d 21; CD83 and MHC-I, d 42), TLR-1, TLR-2 and TLR-6 mRNA levels (d 21, P < 0.05). Cecal microbiome analysis showed that YCWP addition obviously improved cecal microbial composition, as indicated by increasing relative abundance of Fournierella, Psychrobacter and Ruminiclostridium on d 21, and Alistipes and Lactobacillus on d 42, which were positively related with gut development and maturation related indexes (P < 0.05).

Conclusion
Collectively, YCWP promoted yet antibiotic BMD delayed intestinal morphological and immunological development linked with modulating gut microbiome in chickens.
Fluoride-induced testicular and ovarian toxicity: evidence from animal studies
Authors: Talebi Seyedeh Fahimeh , Seify Mohammad , Bhandari Ramji Kumar , Shoorei Hamed , Oskuei Shahram Dabiri 
Published: January 2025

Abstract
Fluoride (F), as a natural element found in a wide range of sources such as water and certain foods, has been proven to be beneficial in preventing dental caries, but concerns have been raised regarding its potential deleterious effects on overall health. Sodium fluoride (NaF), another form of F, has the ability to accumulate in reproductive organs and interfere with hormonal regulation and oxidative stress pathways, contributing to reproductive toxicity. While the exact mechanisms of F-induced reproductive toxicity are not fully understood, this review aims to elucidate the mechanisms involved in testicular and ovarian injury. In males, F exposure at different doses has been associated with reduced testis weight, reduced sperm quality in terms of count, motility, and viability, as well as abnormal sperm morphology and disruption of seminiferous tubules by altering hormone levels (especially testosterone), impairing spermatogenesis, and inducing oxidative stress and zinc deficiency. Similarly, administration of F can impact female reproductive health by affecting ovarian function, hormone levels, oocyte quality, and the regularity of the estrous cycle. However, the impact of F exposure on LH, FSH, and GnRH levels is controversial between males and females. In both males and females, F exerts its adverse effects by triggering apoptosis, autophagy, inflammation, mitochondrial dysfunction, reduction in ATP synthesis, and modulation of important genes involved in steroidogenesis. Furthermore, genetic susceptibility and individual variations in F metabolism may contribute to different responses to fluoride exposure.
Feasibility pilot of a novel coaching intervention to optimize cannabis use for chronic pain management among Veterans
Authors: Boehnke Kevin F. , Bowyer Gabrielle , McAfee Jenna , Smith Tristin , Klida Catherine , Kurtz Vivian , Litinas Evangelos , Purohit Poonam , Arewasikporn Anne , Horowitz Dana , Thomas Laura , Eckersley Jennifer , Railing Mia , Williams David A. , Clauw Daniel J. , Kidwell Kelley M. , Bohnert Amy S. B. , Bergmans Rachel S. 
Published: January 2025

Abstract

Introduction
Chronic pain is common among Veterans, some of whom use cannabis for pain. We conducted a feasibility pilot study of a novel coaching intervention to help Veterans optimize use of medical cannabis products for pain management (NCT06320470).

Methods
The intervention drew from scientific literature, consultation with cannabis experts, Veteran input via a Community Advisory Board, and tenets of motivational interviewing. Participants were Veterans with chronic pain who endorsed current use or interest in using cannabis for pain management. Participants received up to 4 individual coaching sessions via videoconference, spaced approximately 2 weeks apart. We assessed feasibility (adherence, satisfaction, acceptability) and preliminary effects on pain symptoms 14 weeks after baseline. The primary outcome was the Patient Global Impression of Change (PGIC), and exploratory outcomes included domains from the Patient-Reported Outcomes Measurement Information System (PROMIS)-29.

Results
Of 22 enrolled participants, 17 attended 4 coaching sessions, 2 attended 3 sessions, and 2 attended 2 sessions. Among those who completed end of intervention surveys (16/21), 87.5% were very or completely satisfied with the intervention and 81.3% rated coaching as very or extremely helpful. All participants reported improvement on the PGIC, with 63% reporting much or very much improvement. Participants reported statistically significant decreased pain intensity (7.1/10 vs. 5.7/10) and pain interference (T-score 66.3 vs. 61.8), and increased social satisfaction (T-score 41.4 vs. 44.3). Participants noted helpful intervention factors, including co-developing a personalized plan, discussing questions/concerns, and trying different approaches to cannabis-based treatment.

Conclusions
In this feasibility pilot study of coaching on cannabis use for chronic pain among Veterans, participants were satisfied with the intervention and reported clinically significant improvements in pain symptoms. Our results support evaluating this intervention in a larger, efficacy trial.
Evaluation of screening program for hepatocellular carcinoma at a single center
Authors: El-Azab Gasser Ibrahim , El-Helw Ghada Ahmed Ahmed , Elsabaawy Maha Mohamed Ahmed , Kohla Mohamed Ahmed Samy , Omar Yasmin Abdelrahman Muhammed 
Published: January 2025

Abstract

Background
Hepatocellular carcinoma (HCC) is the seventh most common cancer in the world and is a form of liver cancer that starts in the cells of the liver. The best way to increase the chances of survival for people at high risk for HCC is to detect it early through regular monitoring. For monitoring purposes, it is recommended to conduct ultrasound exams every 4 to 6 months, sometimes in combination with alpha-fetoprotein tests.

Aim of the work
Assess the HCC surveillance and its ability to detect HCC patients early on and improve their management.

Patients and methods
The study involved 300 patients of hepatocellular carcinoma (HCC) investigated at Menoufia University’s Institute of National Liver in Egypt. Patients were evaluated using the Liver Cancer of Barcelona Clinic (BCLC) staging system. Furthermore, the patients were classified into three surveillance categories: no surveillance, routine surveillance, and sporadic surveillance.

Results
A substantial difference statistically among the groups that received and did not receive surveillance with consideration for the stage of hepatocellular carcinoma (HCC) in particular was found. Patients who were observed usually got their diagnoses earlier. Those who were not under surveillance frequently had advanced cases of hepatocellular carcinoma upon diagnosis (HCC).

Conclusion
High-risk patients were regularly investigated for having HCC is necessary for early disease detection, appropriate therapy, and improved survival. Consistent monitoring with AFP and ultrasound allows for early detection of HCC.