bluuebunny/crossref_metadata_2025_split huggingface dataset:
Urinary excretion of gluten immunoreactive peptides as an indicator of gastrointestinal function after fasting and dietary provocation in healthy volunteers
Authors: Rodríguez-Ramírez Raquel , Fernández Peralbo María Auxiliadora , Mendía Irati , Long Joshua C. D. , Sousa Carolina , Cebolla Ángel 
Published: August 2024

IntroductionUnderstanding intestinal permeability is paramount for elucidating gastrointestinal health and pathology. The size and nature of the molecule traversing the intestinal barrier offer crucial insights into various acute and chronic diseases, as well as the evolution of some conditions. This study aims to assess the urinary excretion kinetics of gluten immunogenic peptides (u-GIP), a unique class of dietary peptides detectable in urine, in volunteers under controlled dietary conditions. This evaluation should be compared to established probes like lactulose, a non-digestible disaccharide indicative of paracellular permeability, and mannitol, reflecting transcellular permeability.MethodsFifteen participants underwent simultaneous ingestion of standardized doses of gluten (10 g), lactulose (10 g), and mannitol (1 g) under fasting conditions for at least 8 hours pre-ingestion and during 6 hours post-ingestion period. Urine samples were collected over specified time intervals. Excretion patterns were analyzed, and correlations between the lactulose-to-mannitol ratio (LMR) and u-GIP parameters were assessed.ResultsThe majority of u-GIP were detected within the first 12 hours post-ingestion. Analysis of the variability in cumulative excretion across two sample collection ranges demonstrated that lactulose and u-GIP exhibited similar onset and excretion dynamics, although GIP reached its maximum peak earlier than either lactulose or mannitol. Additionally, a moderate correlation was observed between the LMR and u-GIP parameters within the longest urine collection interval, indicating potential shared characteristics among permeability pathways. These findings suggest that extending urine collection beyond 6 hours may enhance data reliability.DiscussionThis study sheds light on the temporal dynamics of u-GIP in comparison to lactulose and mannitol, established probes for assessing intestinal permeability. The resemblance between u-GIP and lactulose excretion patterns aligns with the anticipated paracellular permeability pathway. The capacity to detect antigenic food protein fragments in urine opens novel avenues for studying protein metabolism and monitoring pathologies related to the digestive and intestinal systems.
Dendritic cells transfected with DNA constructs encoding CCR9, IL-10, and type II collagen demonstrate induction of immunological tolerance in an arthritis model
Authors: Fisher Marina S. , Kurilin Vasily V. , Bulygin Aleksey S. , Shevchenko Julia A. , Philippova Julia G. , Taranov Oleg S. , Ivleva Elena K. , Maksyutov Amir Z. , Sennikov Sergey V. 
Published: August 2024

IntroductionRestoring immune tolerance is a promising area of therapy for autoimmune diseases. One method that helps restore immunological tolerance is the approach using tolerogenic dendritic cells (tolDCs). In our study, we analyzed the effectiveness of using dendritic cells transfected with DNA constructs encoding IL-10, type II collagen, and CCR9 to induce immune tolerance in an experimental model of arthritis.MethodsDendritic cell cultures were obtained from bone marrow cells of Balb/c mice. Dendritic cells (DCs) cultures were transfected with pmaxCCR9, pmaxIL-10, and pmaxCollagen type II by electroporation. The phenotype and functions of DCs were studied using enzyme-linked immunosorbent assay (ELISA) and flow cytometry. Migration of electroporated DCs was assessed in vitro. Induction of antigen-collagen induced arthritis (ACIA) was carried out according to the protocol in Balb/c mice. DCs were then administered to ACIA mice. The development of arthritis was monitored by measuring paw swelling with a caliper at different time points. The immunological changes were assessed by analyzing the content of antibodies to type II collagen using enzyme immunoassay. Additionally, a histological examination of the joint tissue was conducted, followed by data analysis.The results are as followsDCs were obtained, characterized by reduced expression of CD80, CD86, and H-2Db (MHC class I), increased expression of CCR9, as well as producing IL-10 and having migratory activity to thymus cells. Transfected DCs induced T-regulatory cells (T-reg) and increased the intracellular content of IL-10 and TGF-β in CD4+T cells in their co-culture, and also suppressed their proliferative activity in response to antigen. The administration of tolDCs transfected with DNA constructs encoding type II collagen, IL-10, and CCR9 to mice with ACIA demonstrated a reduction in paw swelling, a reduction in the level of antibodies to type II collagen, and a regression of histological changes.ConclusionThe study presents an approach by which DCs transfected with DNA constructs encoding epitopes of type II collagen, IL-10 and CCR9 promote the development of antigen-specific tolerance, control inflammation and reduce the severity of experimental arthritis through the studied mechanisms: induction of T-reg, IL-10, TGF-β.
Learning curve of ovarian cystectomy by vaginal natural orifice transluminal endoscopic surgery: a cumulative sum analysis
Authors: Tan Kailiang , Wei Liufei , Deng Zengmei , Yao Desheng , Jiang Li 
Published: August 2024

PurposeTo identify the learning curve in ovarian cystectomy by vaginal natural orifice transluminal endoscopic surgery.MethodsData consist of consecutively ordered patients who underwent ovarian cystectomy via vaginal natural orifice transluminal endoscopic surgery between May 2020 and June 2023. The learning curve of ovarian cystectomy via vaginal natural orifice transluminal endoscopic surgery was measured in terms of the operating time adjusted by multivariate linear regression. A cumulative sum analysis was performed to establish the learning curve. Patients’ characteristics and surgical outcomes were compared based on the inflection points of this curve.ResultsThe learning curve was divided into two unique phases: phase 1 (1–26 patients), and phase 2 (27–40 patients). The expected operating time in phase 2 was shorter than in phase 1 (86.4 ± 11.2 min vs. 102.0 ± 22.7 min, p = 0.021). The time to first postoperative flatus was shorter in phase 2 compared with phase 1 (14.6 ± 6.5 h vs. 20.6 ± 6.3 h, respectively, p = 0.008). No significant differences were observed in terms of patient’s age, BMI, tumor size, parity, bilateral ovarian tumor, pathological diagnoses, estimated blood loss, postoperative pain score, or perioperative complications between the two phases.ConclusionProficiency in ovarian cystectomy by vaginal natural orifice transluminal endoscopic surgery was achieved after 26 surgeries based on cumulative sum analysis. These findings may provide insight for structured training programs of ovarian cystectomy via vaginal natural orifice transluminal endoscopic surgery.
Antibiotic resistance and virulence characteristics of Vibrio vulnificus isolated from Ningbo, China
Authors: Xu Xiaomin , Liang Shanyan , Li Xin , Hu Wenjin , Li Xi , Lei Liusheng , Lin Huai 
Published: August 2024

BackgroundVibrio vulnificus (V. vulnificus) is a deadly opportunistic human pathogen with high mortality worldwide. Notably, climate warming is likely to expand its geographical range and increase the infection risk for individuals in coastal regions. However, due to the absence of comprehensive surveillance systems, the emergence and characteristics of clinical V. vulnificus isolates remain poorly understood in China.MethodsIn this study, we investigate antibiotic resistance, virulence including serum resistance, and hemolytic ability, as well as molecular characteristics of 21 V. vulnificus isolates collected from patients in Ningbo, China.Results and discussionThe results indicate that all isolates have been identified as potential virulent vcg C type, with the majority (16 of 21) classified as 16S rRNA B type. Furthermore, these isolates exhibit a high level of antibiotic resistance, with 66.7% resistance to more than three antibiotics and 61.9% possessing a multiple antibiotic resistance (MAR) index exceeding 0.2. In terms of virulence, most isolates were categorized as grade 1 in serum resistance, with one strain, S12, demonstrating intermediate sensitivity in serum resistance, belonging to grade 3. Whole genome analysis disclosed the profiles of antibiotic resistance genes (ARGs) and virulence factors (VFs) in these strains. The strains share substantial VF genes associated with adherence, iron uptake, antiphagocytosis, toxin, and motility. In particular, key VFs such as capsule (CPS), lipopolysaccharide (LPS), and multifunctional autoprocessing repeats-in-toxin (MARTX) are prevalent in all isolates. Specifically, S12 possesses a notably high number of VF genes (672), which potentially explains its higher virulence. Additionally, these strains shared six ARGs, namely, PBP3, adeF, varG, parE, and CRP, which likely determine their antibiotic resistance phenotype.ConclusionOverall, our study provides valuable baseline information for clinical tracking, prevention, control, and treatment of V. vulnificus infections.
Assessing causal association of circulating micronutrients and systemic lupus erythematosus susceptibility: a Mendelian randomization study
Authors: Huang Shihui , Wei Xuemei , Qin Fang , Yuan Zongxiang , Mo Chuye , Kang Yiwen , Huang Chunlin , Jiang Junjun , Ye Li 
Published: August 2024

BackgroundPrevious studies showed the conflicting associations between circulating micronutrient levels and systemic lupus erythematosus (SLE). Therefore, we aimed to clarify the causal association between circulating micronutrient levels and the risk of SLE by two-sample Mendelian randomization (MR) analysis.Methods56 single nucleotide polymorphisms (SNPs) significantly associated with 14 circulating micronutrients (vitamin A, B6, B9, B12, C, D and E, phosphorus, calcium, magnesium, copper, iron, zinc, and selenium) in published genome-wide association studies (GWAS) were used as instrumental variables (IVs). And summary statistics related to SLE were obtained from the IEU OpenGWAS database. We used the MR Steiger test to estimate the possible causal direction between circulating micronutrients and SLE. In the MR analysis, inverse variance weighting (IVW) method and the Wald ratio was as the main methods., Moreover, the MR-Pleiotropy residuals and outliers method (MR-PRESSO), Cochrane’s Q-test, MR-Egger intercept method and leave-one-out analyses were applied as sensitivity analyses. Additionally, we conducted a retrospective analysis involving the 20,045 participants from the Third National Health and Nutritional Examination Survey (NHANES III). Weight variables were provided in the NHANES data files. Univariate and multivariate logistic regression analyses were performed to determine the associations between circulating micronutrients and SLE.ResultsThe MR estimates obtained from the IVW method revealed potential negative correlations between circulating calcium (OR: 0.06, 95% CI: 0.01–0.49, P = 0.009), iron levels (OR: 0.63, 95% CI: 0.43–0.92, P = 0.016) and the risk of SLE. The results remained robust, even under various pairs of sensitivity analyses. Our retrospective analysis demonstrated that the levels of vitamin D, serum total calcium, and serum iron were significantly lower in SLE patients (N = 40) when compared to the control group (N = 20,005). Multivariate logistic regression analysis further established that increased levels of vitamin D and serum total calcium served as protective factors against SLE.ConclusionOur results provided genetic evidence supporting the potential protective role of increasing circulating calcium in the risk of SLE. Maintaining adequate levels of calcium may help reduce the risk of SLE.
Bidirectional relationship between Helicobacter pylori infection and nonalcoholic fatty liver disease: insights from a comprehensive meta-analysis
Authors: Zhang Daya , Wang Qi , Bai Feihu 
Published: August 2024

BackgroundHelicobacter pylori (H. pylori) infection and nonalcoholic fatty liver disease (NAFLD) represent significant concerns in global health. However, the precise relationship between H. pylori and NAFLD remains a subject of ongoing debate. This study endeavors to elucidate the association between H. pylori infection and the susceptibility to NAFLD. Furthermore, we aim to investigate the interplay among H. pylori infection, NAFLD, and metabolic syndrome (MetS).MethodsWe conducted an extensive search of the PubMed, EMBASE, and Web of Science databases spanning from inception to January 2024. Our examination focused on rigorous studies investigating the correlation between H. pylori infection and NAFLD. Utilizing a random-effects model, we computed the pooled odds ratio (OR) and corresponding 95% confidence interval (CI). Additionally, we assessed statistical heterogeneity, performed sensitivity analyses, and scrutinized the potential for publication bias.ResultsThirty-four studies involving 175,575 individuals were included in our meta-analysis. Among these, 14 studies (involving 94,950 patients) demonstrated a higher incidence of NAFLD in H. pylori infection-positive individuals compared to H. pylori infection-negative individuals [RR = 1.17, 95% CI (1.10, 1.24), Z = 4.897, P &lt; 0.001]. Seventeen studies (involving 74,928 patients) indicated a higher positive rate of H. pylori infection in patients with NAFLD compared to those without NAFLD [RR = 1.13, 95% CI (1.02, 1.24), Z = 2.395, P = 0.017]. Sensitivity analyses confirmed the robustness of these findings, and funnel plot analysis revealed no significant publication bias. Furthermore, we observed associations between H. pylori infection or NAFLD and various metabolic factors, including body mass index (BMI), blood pressure, lipids, liver function, and kidney function.ConclusionOur meta-analysis presents evidence supporting a reciprocal relationship between H. pylori infection and the susceptibility to NAFLD. Nevertheless, additional investigations are warranted to bolster this correlation and unravel the underlying mechanisms involved.
The effects of raspberry consumption on anthropometric indices and liver function tests in adults: a GRADE-assessed systematic review and meta-analysis
Authors: Shahraki Jazinaki Mostafa , Barghchi Hanieh , Rahbarinejad Pegah , Pahlavani Naseh 
Published: August 2024

BackgroundIn recent years, the therapeutic effects of raspberry have been the subject of several randomized control trials (RCTs). However, there is no consensus about the effect of raspberry consumption on anthropometric indices and liver function tests. So, the present review aims to investigate this effectiveness by conducting a meta-analysis.MethodsPubMed, Web of Science, and Scopus databases were searched to identify eligible randomized control trials (RCTs) up to March 2024. The overall effect sizes were estimated using the random-effects model as weighted mean difference (WMD) and 95% confidence intervals (CIs).ResultsNine studies (10 arms) with 355 participants were eligible for inclusion in this review. This meta-analysis showed that raspberry consumption did not lead to significant changes in anthropometric indices (weight, body mass index, and waist circumference) and liver function tests (aspartate aminotransferase and alanine aminotransferase).ConclusionThis review revealed that raspberry consumption had no significant impact on anthropometric indices or liver function tests. However, more RCTs with a larger sample size and higher sensitivity are needed to draw definite conclusions.Systematic review registration: https://www.crd.york.ac.uk/prospero/display_record.php?RecordID=477568, PROSPERO ID: CRD42023477568.
Confirming the efficacy and safety of CDK4/6 inhibitors in the first-line treatment of HR+ advanced breast cancer: a systematic review and meta-analysis
Authors: Guan Xin , Li Mengyuan , Ji Xinyue , Wang Yufei , Tian Lei 
Published: August 2024

Objective: Cyclin-dependent kinase (CDK) 4 and 6 inhibitors (abemaciclib, palbociclib and ribociclib) have been recommended in the first-line treatment of hormone receptor-positive (HR+) breast cancer in China. Our study aims to evaluate the efficacy and safety of CDK4/6 inhibitors by processing survival data using fractional polynomial modeling methods.Methods: Phase II or III randomized controlled trials in treatment-naive HR + patients with advanced breast cancer were systematically searched through the preset search strategy. The fractional polynomial (FP) model was used to relax the proportional hazard assumption and obtain time-varying hazard ratio (HR). Progression-free life years (PFLYs) and life years (LYs) were calculated from the area under curve (AUC) of the predicted progression-free survival (PFS) and overall survival (OS) curves to evaluate the long-term efficacy benefit. Odds ratio (OR) of grade≥3 adverse events were analyzed for safety outcomes.Results: 6 randomized controlled trials with 2,638 patients were included. The first-order FP model (p = −1) and the first-order FP model (p = 1) were used to calculate the time-varying HR of PFS and OS, respectively. Extrapolating to 240 months, abemaciclib obtained a PFS benefit of 3.059 PFLYs and 6.275 LYs by calculating the AUC of the PFS and OS curves. Palbociclib obtained 2.302 PFLYs and 6.351 LYs. Ribociclib obtained 2.636 PFLYs and 6.543 LYs. In terms of safety, the use of CDK4/6 inhibitors resulted in a higher risk of adverse events (OR = 9.84, 95% CI: 8.13–11.95), especially for palbociclib (OR = 14.04, 95% CI: 10.52–18.90).Conclusion: The use of CDK4/6 inhibitors in treatment-naive patients with HR + advanced breast cancer significantly improves survival, but also increases the risk of adverse events. Abemaciclib and ribociclib may be the best options for prolonging PFS and OS in treatment-naïve patients, respectively.
Effectiveness and safety of Chinese herbal footbaths as an adjuvant therapy for dysmenorrhea: a systematic review and meta-analysis
Authors: Tian Xiaoping , Wei Jingwen , Zhuang Yijia , Lin Xiaoding , Liu Liu , Xia Jun , Huai Wenying , Xiong Ying , Chen Yunhui 
Published: August 2024

ObjectivesTo evaluate the effectiveness and safety of Chinese herbal footbaths (CHF) as an adjunctive therapy in managing dysmenorrhea.MethodsTen electronic databases were searched to identify eligible randomized clinical trials (RCTs) from inception until June 2023. Outcome measurements encompassed the total effective rate, visual analog scale (VAS) score of pain intensity, Cox menstrual symptom scale (CMSS) score, symptom score, Traditional Chinese Medicine (TCM) syndrome scale, and any reported adverse events. The methodological quality of the included studies was assessed with the Cochrane collaboration tool. Review Manager 5.3 software was employed for quantitative synthesis, and funnel plots were utilized to evaluate potential reporting bias.ResultsEighteen RCTs with 1,484 dysmenorrhea patients were included. The aggregated results suggested that the adjunctive CHF could significantly ameliorate dysmenorrhea, as evident from the improved total effective rate [risk ratio (RR) 1.18, 95% confidence interval (CI): 1.12 to 1.23, P &lt; 0.00001], VAS (MD 0.88, 95% CI: 0.68 to 1.09, P &lt; 0.00001), CMSS (MD 3.61, 95% CI: 2.73 to 4.49, P &lt; 0.00001), symptom score (SMD 1.09, 95% CI: 0.64 to 1.53, P &lt; 0.00001), and TCM syndrome scale (MD 3.76, 95% CI: 2.53 to 4.99, P &lt; 0.0001). In addition, CHF presented fewer adverse events with a better long-term effect (RR 1.34, 95% CI: 1.11 to 1.63, P &lt; 0.01) and diminished recurrence rate (RR 0.19, 95% CI: 0.09 to 0.39, P &lt; 0.0001).ConclusionCurrent evidence implies that CHF may be an effective and safe adjunctive therapy for patients with dysmenorrhea. However, the methodological quality of the studies included was undesirable, necessitating further verification with more well-designed and high-quality multicenter RCTs.Systematic Review Registration:https://www.crd.york.ac.uk/PROSPERO/display_record.php?RecordID=188256, identifier registration number.
Pakistan’s national COVID-19 response: lessons from an emergent response to the pandemic
Authors: Khan Adnan Ahmad , Abdullah Mujahid , Khan Romesa , Kazmi Twangar , Sultan Faisal , Aamir Shirin , Khawaja Aamir Ashraf , Khan Ayesha 
Published: August 2024

IntroductionIn 2020, Pakistan faced the formidable challenge of the COVID-19 pandemic with an existing yet disjointed healthcare infrastructure, that included by over 18,000 public and an estimated 75,000 private health facilities and some elements of an epidemic surveillance and response system. This descriptive study examines how Pakistan developed a COVID-19 response, driven by establishing a central coordination and decision-making mechanism to overcome these systemic challenges.MethodsThe study is based on interviews and interactions of the many actors in the response by the authors, who also participated in nearly all proceedings of the National Command and Operation Centre (NCOC) and many of the National Coordination Committee (NCC). This information is supplemented by reviewing documents, reports, news items, media and social media, and journal articles.ResultsThe study highlights the critical role of political arrangement, where the NCC, comprising of ministers, bureaucrats, and military personnel, facilitated federal and provincial integration. The NCC found resources and set policy. Its direction was implemented by the NCOC, a top-down yet inclusive platform, integrated political, military, and civil society actors, to ensure cohesive decision-making and implementation. It provided technical guidance, harnessed data for strategic decisions and held implementers accountable. At its peak, the NCOC boasted nearly 300 personnel, including high-ranking military officers, a stark contrast to the limited staffing in most ministries. In addition, the response’s success is attributed to the perception of COVID-19 as an existential threat, leading to unprecedented collaboration and decisive actions that were enforced authoritatively.ConclusionPakistan’s experience offers valuable insights for proactive management of health emergencies in resource-limited settings. It underscores the necessity for inter-sectoral dialog and data-driven policy implementation, especially in the context of political economies where activity-driven governance often overshadows objective-driven policy execution. However, the lessons from the COVID-19 response, including a blueprint for future epidemic responses and lessons for use of data and evidence in developing country health systems, if not institutionalized, risk being lost in the post-pandemic era.