bluuebunny/crossref_metadata_2025_split huggingface dataset:
Alcohol consumption and its association with cancer, cardiovascular, liver and brain diseases: a systematic review of Mendelian randomization studies
Authors: Bouajila Naouras , Domenighetti Cloé , Aubin Henri-Jean , Naassila Mickael 
Published: November 2024

BackgroundThe health effects of alcohol consumption, particularly regarding potential protective benefits of light to moderate intake compared to abstinence, remain a subject of ongoing debate. However, epidemiological studies face limitations due to imprecise exposure measurements and the potential for bias through residual confounding and reverse causation. To address these limitations, we conducted a systematic review of Mendelian Randomization (MR) studies examining the causal relationship between alcohol consumption and cancers, cardiovascular, liver, and neurological diseases.MethodologyWe searched PubMed, ScienceDirect and Embase and Europe PMC up to 05/2024 for MR studies investigating the association of genetically predicted alcohol consumption with cancers, cardiovascular, liver and neurological diseases. We assessed methodological quality based on key elements of the MR design a genetic association studies tool.ResultsWe included 70 MR studies that matched our inclusion criteria. Our review showed a significant association of alcohol consumption with multiple cancers such as oral and oropharyngeal, esophageal, colorectal cancers, hepatocellular carcinoma and cutaneous melanoma. While the available studies did not consistently confirm the adverse or protective effects of alcohol on other cancers, such as lung cancer, as suggested by observational studies. Additionally, MR studies confirmed a likely causal effect of alcohol on the risk of hypertension, atrial fibrillation, myocardial infraction and vessels disease. However, there was no evidence to support the protective effects of light to moderate alcohol consumption on cognitive function, Alzheimer's disease, and amyotrophic lateral sclerosis, as reported in observational studies while our review revealed an increased risk of epilepsy and multiple sclerosis. The available studies provided limited results on the link between alcohol consumption and liver disease.ConclusionsDespite the valuable insights into the causal relationship between alcohol consumption and various health outcomes that MR studies provided, it is worth noting that the inconsistent ability of genetic instrumental variables to distinguish between abstainers, light and moderate drinkers makes it difficult to differentiate between U or J-shaped vs. linear relationships between exposure and outcome. Additional research is necessary to establish formal quality assessment tools for MR studies and to conduct more studies in diverse populations, including non-European ancestries.Systematic Review Registrationwww.crd.york.ac.uk/prospero/display_record.php?ID=CRD42021246154, Identifier: PROSPERO (CRD42021246154).
Safety, immunogenicity and immune-persistence of a lyophilized human rabies vaccine (Vero cells) under Zagreb and Essen regimens: a randomized, open-label, controlled phase III clinical trial in healthy participants aged 10–60 years in China
Authors: Liang Zhenzhen , Chen Xu , Xing Bo , Hu Xiaosong , Liu Miaomiao , Zhang Xinpei , Shen Yugang , Wang Yan , Chen Yingping , Lv Huakun , Mao Yu 
Published: November 2024

BackgroundRabies continues to be a significant global public health concern, particularly in the Asia region where it is associated with high mortality rate. The administration of effective vaccination is essential in preventing this potentially fatal viral infection. The objective of this study was to evaluate the immunogenicity and safety of two rabies vaccination schedules: the Zagreb (2–1–1) and Essen (1–1–1–1–1) regimens, in a cohort of healthy Chinese individuals aged 10-60 years.MethodsWe conducted a randomized, open-label, controlled, non-inferiority phase 3 trial from July 2021 to November 2022, enrolling a total of 1200 participants. Participants were randomly assigned to receive either the Zagreb or Essen vaccination regimen. The primary outcomes were safety, immunogenicity, and immune persistence. Safety was monitored through adverse event reporting, while immunogenicity was determined by measuring rabies-virus-neutralizing antibody (RVNA) concentrations using the rapid fluorescent focus inhibition test (RFFIT). Immune persistence was evaluated at 3, 6, and 12 months post-vaccination.ResultsThe two vaccination regimens exhibited comparable safety records, with mild and transient adverse events predominantly occurring within 0-3 days post-vaccination. The Zagreb regimen demonstrated non-inferiority in terms of seroconversion rates and geometric mean concentrations (GMCs) of antibodies compared to the Essen regimen at both 14 days post-first vaccination and 14 days post-full vaccination. Additionally, both groups displayed nearly 100% seropositivity rate at 3,6, and 12 months. No serious adverse events associated with vaccination were reported.ConclusionThe findings of this Phase 3 clinical trial provide compelling evidence that the Zagreb regimen is a feasible alternative when compared to the Essen regimen for rabies vaccination, offering a more pragmatic and cost-efficient approach to rabies prevention and control.Clinical trial registrationhttp://www.chinadrugtrials.org.cn, identifier CTR20210426.
Immunotherapy plus chemotherapy versus chemotherapy alone in the first-line treatment for advanced gastric cancer/gastroesophageal junction cancer: a real-world retrospective study
Authors: Xu Qian , Yi Dan , Jia Caiyan , Kong Fanming , Jia Yingjie 
Published: November 2024

BackgroundImmunotherapy offers new hope for improved survival in patients with advanced gastric cancer. Although large randomized controlled trials (RCTs) have been conducted to explore the efficacy and safety of first-line immunotherapy plus chemotherapy versus chemotherapy alone for advanced gastric cancer, the results are not completely consistent. And the strict inclusion criteria of RCTs lead to limited extrapolation. Therefore, it is of great significance to continue to conduct real-world studies comparing the clinical efficacy and safety of immunotherapy combined with chemotherapy versus chemotherapy alone in advanced gastric cancer.MethodsThis retrospective study included patients with HER-2 negative, unresectable advanced or recurrent gastric/gastroesophageal junction cancer (GC/GEJC) who received first-line immune checkpoint inhibitors (ICIs) in combination with chemotherapy or chemotherapy alone between January 1, 2018 to May 31, 2023. Progression-free survival (PFS), overall survival (OS), overall response rate (ORR), disease control rate (DCR) and adverse events (AEs) were compared between two groups.ResultsA total of 210 patients were enrolled in the combination treatment group (n=100) and chemotherapy alone group (n=110). After 12 months of follow-up, median PFS (mPFS) was 270 days (95%CI 177.510-362.490) in the chemotherapy alone group and 357 days (95%CI 250.103-463.897) in the combination treatment group (P&lt;0.05). The median OS (mOS) was 14.9 months (95%CI 9.831-17.769) in the chemotherapy alone group and 15 months (95%CI 12.386-17.614) in the combination treatment group (P&gt;0.05). There was no statistically significant difference in ORR between two groups (P=0.050). The DCR was 14.5% in the chemotherapy alone group and 38% in the combination treatment group (P&lt;0.05). Subgroup analyses showed that primary tumor location of GEJC, ECOG PS of 1, without liver metastasis, and chemotherapy plus ICIs were associated with PFS benefit. Cox multivariate analysis showed that only surgery or not was correlated with patients’ prognosis (P&lt;0.05). Most of AEs were grade 1-2 and manageable.ConclusionsCompared with chemotherapy alone, first-line ICIs combined with chemotherapy in patients with advanced GC/GEJC could greatly prolong PFS, but OS was not significantly improved, and the AEs were manageable.
Clinical features of anti-SAE1 antibody-positive myositis and interstitial lung disease: a multicenter, retrospective study in Taiwan
Authors: Hsiao Chao-Yang , Tseng Shu-Chi , Hsu Chung-Yuan , Chiu Li-Chung , Su Li-Jen , Chan Tien-Ming 
Published: November 2024

IntroductionThe clinical characteristics of patients positive for anti-small ubiquitin-like modifier 1-activating enzyme subunit 1 (SAE1) antibodies and diagnosed with idiopathic inflammatory myopathies (IIMs) vary across different cohorts and ethnicities, particularly concerning interstitial lung disease (ILD). We aimed to assess the clinical utility of the line immunoblot assay (LIA) in detecting anti-SAE1 autoantibodies and evaluate the clinical relevance and chronology of ILD development in relation to SAE1 autoantibody positivity among Taiwanese patients.MethodsWe retrospectively conducted a population-based cohort analysis involving 6,496 patients who visited Chang Gung Memorial Health System across Taiwan from May 2018 to December 2021. Patients were assayed for myositis-specific autoantibodies (MSAs) and myositis-associated autoantibodies (MAAs) using the LIA method, and the antinuclear antibody (ANA) indirect immunofluorescence (IIF) method was used to evaluate ANA patterns. Of these, 70 SAE1-positive patients (1.08%) were included and followed up until December 2023. Associations with clinical characteristics and final diagnosis, particularly ILD, were assessed.ResultsAmong the 70 SAE1-positive patients, 10 (14.3%) were strongly positive and 60 (85.7%) were weakly positive. In the strong positive group, 70% (7/10) were diagnosed with IIM, with most (5/7) showing a concordant ANA IIF pattern (speckled type). Six patients presented ILD either before (1/6) or after (5/6) IIM diagnosis; the majority (4/6) were classified as organizing pneumonia. The remaining 30.0% (3/10) had connective tissue disease (CTD) other than IIM without detectable ILD during follow-up, and none demonstrated a concordant ANA IIF pattern. In the weakly positive group, only 5.0% (3/60) had IIM and 3.3% (2/60) had ILD. The positive predictive value for strong positive SAE1 autoantibodies in diagnosing IIM was significantly higher than for weak positives (70.0% vs. 5.0%; p &lt; 0.001).ConclusionsThe study suggests that strong positive SAE1 autoantibodies detected via LIA are more closely associated with IIM compared to weak positive results. A high prevalence of ILD was observed among strong positive Taiwanese patients, indicating the need for prompt screening. Patients with weak positive or discordant ANA IIF results may represent false positives with a lower ILD risk.
Integrated analysis of single-cell, spatial and bulk RNA-sequencing identifies a cell-death signature for predicting the outcomes of head and neck cancer
Authors: Pan Yue , Fei Lei , Wang Shihua , Chen Hua , Jiang Changqing , Li Hong , Wang Changsong , Yang Yao , Zhang Qinggao , Chen Yongwen 
Published: November 2024

BackgroundCell death plays an essential role in carcinogenesis, but its function in the recurrence and postoperative prognosis of head and neck cancer (HNC), which ranks as the 7th most common malignancy globally, remains unclear.MethodsData from five main subtypes of HNC related single-cell RNA sequencing (scRNA-seq) were recruited to establish a single-cell atlas, and the distribution of cell death models (CDMs) across different tissues as well as cell subtypes were analyzed. Bulk RNA-seq from the Cancer Genome Atlas Program (TCGA) dataset was subjected to a machine learning-based integrative procedure for constructing a consensus cell death-related signature risk score (CDRscore) model and validated by external data. The biofunctions including different expression analysis, immune cell infiltration, genomic mutations, enrichment analysis as well as cellchat analysis were compared between the high- and low- risk score groups categorized by this CDRscore model. Finally, samples from laryngeal squamous cell cancer (LSCC) were conducted by spatial transcriptomics (ST) to further validate the results of CDRscore model.ResultsT cells from HNC patients manifested the highest levels of cell death while HPV infection attenuates malignant cell death based on single-cell atlas. CDMs are positively correlated with the tumor-cell stemness, immune-related score and T cells are infiltrated. A CDRscore model was established based on the transcription of ten cell death prognostic genes (MRPL10, DDX19A, NDFIP1, PCMT1, HPRT1, SLC2A3, EFNB2, HK1, BTG3 and MAP2K7). It functions as an independent prognostic factor for overall survival in HNC and displays stable and powerful performance validated by GSE41613 and GSE65858 datasets. Patients in high CDRscore manifested worse overall survival, more active of epithelial mesenchymal transition, TGF-β-related pathways and hypoxia, higher transcription of T cell exhausted markers, and stronger TP53 mutation. ST from LSCC showed that spots with high-risk scores were colocalized with TGF-β and the proliferating malignant cells, additionally, the risk scores have a negative correlation with TCR signaling but positive association with LAG3 transcription.ConclusionThe CDRscore model could be utilized as a powerful prognostic indicator for HNC.
ZNF350 gene polymorphisms promote the response to Peg-IFNα therapy through JAK-STAT signaling pathway in patients with chronic hepatitis B
Authors: Guo Jianhui , Guo Shaoying , Chen Tianbin , Zeng Yongbin , Fu Ya , Ou Qishui 
Published: November 2024

BackgroundThe varying individual responses to Pegylated interferon-α (Peg-IFNα) in patients with chronic hepatitis B (CHB) pose significant hurdles in treatment optimization, and the underlying mechanisms remain unclear.ObjectiveWe aimed to identify genetic polymorphisms influencing the efficacy of Peg-IFNα in patients with HBeAg-positive CHB, with the goal to predict Peg-IFNα response before treatment.MethodsWe employed an Asian Screening Array analysis involving 124 HBeAg-positive CHB patients treated with Peg-IFNα. We conducted assessment of immunological markers and mRNA expression of pivotal genes, establishing correlations with SNPs, functional genes of SNPs, and efficacy of Peg-IFNα therapy. In vitro experiments were performed to verify the functional involvement of the candidate SNPs.ResultsThe G allele presented in rs2278420 and rs6509607 were significantly more common in patients who achieved a complete response (CR) compared to those who had a suboptimal response (SR), and linked to an increased rates of HBeAg loss following Peg-IFNα treatment (all p &lt; 0.05). Additionally, the mRNA level of ZNF350 varied notably across different genotypes of both SNPs as determined by eQTL analysis, and showed higher expression in patients achieved a SR (all p &lt; 0.05). In vitro investigations with IFNα stimulation showed that the mRNA level of SOCS3 was elevated in patients with rs2278420 genotype AA, similarly, mRNA levels of PKR, STAT2, SOCS1, SOCS3, PIAS1, PTPN6 and TRIM8 were heightened in patients with rs6509607 genotype AA compared to those with genotypes (AG+GG) (all p &lt; 0.05).ConclusionThe G allele of rs2278420 and rs6509607 were associated with mRNA level of ZNF350, with an increased probability of Peg-IFNα response in HBeAg-positive CHB patients, likely through the modulation of JAK-STAT signaling pathway.
Clinical study on the safety and efficacy of remimazolam in hysteroscopic surgery under general anesthesia in elderly patients
Authors: Xie Manjie , Zeng Fanrui , Tian Qiao , Deng Huiwei , Tao Shanqing 
Published: November 2024

ObjectiveTo evaluate the safety and efficacy of remimazolam in hysteroscopic surgery in elderly patients.MethodsFollowing hysteroscopic surgery under selected general anesthesia, 60 elderly patients ASA (American Society of Anesthesiologists) class II–III, &gt;65 years old were randomly assigned to one of two groups: the R group (remimazolam) or the C group (propofol), each with 30 patients. Sufentanil 0.1 μg/kg was given 5 min before the operation, remimazolam 0.2 mg/kg intravenously in Group R, then 0.5~1 mg/(kg.h) by pump, propofol 2 mg/kg intravenously in group B, and then 4~8 mg/(kg.h) by pump. Maintain BIS (Bispectral index) 40~70, add remimazolam 0.05 mg/kg or propofol 0.5 mg/kg when the patient is in motion, and stop the administration at the end of the operation. Record the patients' HR, MAP, RR, SpO2, PETCO2, and BIS values at entry (T0), before induction administration (T1), 1 min after administration (T2), 5 min after administration (T3), when stopping administration (T4), when awakening (T5), and 1 min after awakening (T6), as well as the onset time after administration, the awakening time, the success rate of sedation, and the number and dose of additional medications. Reactions are adverse (hypotension, hypertension, respiratory depression incidence, injection pain, nausea and vomiting following surgery, etc.).ResultsThe two groups' respective anesthetic success rates were comparable overall. In addition to having a higher BIS value and more extra medications than group C, group R experienced less incidence of respiratory depression, injection pain, and intraoperative hypotension.ConclusionRemimazolam, which is equivalent to propofol in terms of safety and efficacy for older patients undergoing hysteroscopic surgery, should be further promoted and used.
Impact of fat intake on [18F]AlF-NOTA-FAPI-04 uptake in normal abdominal organs
Authors: Dai Jiashun , Zhou Wanjing , Liu Huaping , Jiang Chengzhi , Ye Hui 
Published: November 2024

Purpose[18F]AlF-NOTA-FAPI-04 demonstrates significant physiological uptake in the gallbladder and biliary tract system, representing a limitation of this positron emission tomography (PET) tracer. The aim of this study was to evaluate the impact of milk consumed prior to a PET/CT scan on [18F]AlF-NOTA-FAPI-04 uptake in normal abdominal organs.Materials and methodsA total of 86 patients who underwent [18F]AlF-NOTA-FAPI-04 PET/CT imaging took part in this single-center retrospective clinical study at the Hunan Cancer Hospital between December 2020 and August 2021. Patients were divided into two groups according to their pre-PET scan diet: treated group, who consumed 250 mL of milk 10 ± 5 min after the tracer injection, while the control group was permitted no food intake subsequent to the radiotracer administration. The mean standardized uptake value (SUVmean) of gallbladder, liver, small intestine and pancreas were measured in 18F-FAPI and 18F-FDG PET/CT.ResultsThere was a statistically significant difference in the 18F-FAPI uptake in the gallbladder between the treated group and the control group (p &lt; 0.001). The average SUVmean in the treated group was 2.19 ± 2.01, which was significantly lower than the average SUVmean of 10.04 ± 9.66 in the control group. In the subgroup analysis of patients who underwent paired [18F]FDG and [18F]FAPI PET/CT scans, the 18F-FAPI uptake of liver and small intestine was significantly lower than the 18F-FDG uptake in both the treated group and the control group (p &lt; 0.001).ConclusionThis study suggests that milk consumption decreases physiological 18F-FAPI uptake in the gallbladder, potentially enhancing the diagnostic accuracy for gallbladder cancer.
Accreditation of pharmacy programs and its impact on SPLE success and pharmacist readiness in Saudi Arabia
Authors: Almaghaslah Dalia 
Published: November 2024

AimThe impact of pharmacy program accreditation on the Saudi Pharmacists Licensure Examination (SPLE) pass rates and overall pharmacist readiness was investigated.MethodsA cross-sectional retrospective study was conducted. Data on SPLE pass rates were obtained from the Saudi Commission for Health Specialties (SCFHS) 2024 report. Pharmacy colleges were categorized into five groups based on their students' average SPLE scores. Information on the national i.e., the Evaluation and Training Evaluation Center (ETEC) and international i.e., the American Council for Pharmacy Education (ACPE) and the Canadian Council for Accreditation of Pharmacy Programs (CCAPP) accreditation status of these colleges was also collected.ResultsHigher average SPLE scores (mean = 563, SE = 43.4) were observed in accredited colleges (either national or international) compared to non-accredited colleges (mean = 533, SE = 33.6), with a significant difference noted [t(22) = −2.149, p = 0.042]. Higher average SPLE scores (mean = 581.8, SE = 18.9) were also found in colleges with multiple accreditations compared to those with fewer or no accreditations (mean = 548.02, SE = 18.9), though this difference was not statistically significant [t(25) = −1.8, p = 0.086].Discussion and conclusionIt was demonstrated that accreditation, whether national or international, is associated with higher SPLE pass rates, indicating a positive impact on exam performance. National accreditation by ETEC alone was found to be sufficient for improving SPLE scores and ensuring pharmacist readiness, whereas dual or international accreditations did not provide additional benefits in this context.
Toward making the field talk: assessing the relationship between digital technology and sustainable food production in agricultural regions
Authors: Khan Nawab , Xu Xuanguo , Khayyam Muhammad , Raziq Abdul 
Published: November 2024

IntroductionThe global food system faces numerous challenges, including population growth, pandemics, climate change, natural disasters, and economic instability. These challenges have a profound impact on agriculture, with climate change leading to unpredictable weather and more frequent extreme events that threaten crop yields and farming sustainability. Farmers are also grappling with rising input costs and market volatility, intensifying the need for improved productivity and efficiency.PurposeConsidering these challenges, digital technology, particularly mobile internet (MI), is emerging as a key tool for achieving sustainable agriculture by enhancing productivity, efficiency, and cost-effectiveness. While much research has focused on the effects of MI on agricultural inputs, prices, and operational efficiency, there is limited understanding of its direct impact on food production outcomes. This study aims to fill this gap by examining the influence of MI usage on crop production.MethodThe study utilizes data from 660 farmers across two provinces of Pakistan. Propensity Score Matching (PSM) and linear regression models are employed to assess the impact of MI usage on food production.ResultsThe analysis reveals a significant positive effect of MI usage on crop production, with MI users experiencing a 13.30% increase in crop yield compared to non-users. The heterogeneity analysis shows varying impacts among different farmer groups: young farmers see a 13.50% increase, less-educated farmers a 15.27% rise, larger-scale farmers a 23.80% boost, and those in economically developed villages a 10.50% improvement per hectare compared to non-users.ConclusionThe study highlights the potential of MI in boosting crop production, particularly for specific farmer demographics. Policymakers should prioritize the development of MI infrastructure in rural areas and collaborate with research institutions, agricultural cooperatives, and enterprises to design interventions, such as financial support and technical assistance, that can help farmers fully leverage the benefits of digital technology.