bluuebunny/crossref_metadata_2025_split huggingface dataset:
Lipid-lowering drugs, circulating inflammatory factors, and atrial fibrillation: a mediation Mendelian randomization study
Authors: Ou Guangyang , Zhang Yi , Cai Huzhi , Yao Kunpeng , Qiu Zerui , Chen Yaowu , Yang Yang , Chen Qingyang , Chen Xinyu 
Published: November 2024

BackgroundPrevious studies have shown an association between lipid-lowering drugs, circulating inflammatory factors, and atrial fibrillation (AF), but the specific effects of lipid-lowering drugs on AF and whether they can be mediated by circulating inflammatory factors remain unclear.MethodsWe collected 10 genetic variants encoding lipid-lowering drug targets (LDLR, HMGCR, PCSK9, NPC1L1, APOB, APOB, ABCG5, ABCG8, LPL, APOC3, and PPARA) and AF based on genome-wide association study (GWAS) summary statistics. Drug target Mendelian randomization (MR) was used to explore the causal relationship between lipid-lowering drugs and AF. In addition, we performed a mediation analysis of 91 circulating inflammatory factors to explore potential mediators. Sensitivity analyses were performed to verify the reliability of the MR Results by MR-Egger intercept test, Cochran's Q test and leave-one-out test.ResultsThe results of IVW method showed that LPL agonist had a protective effect on AF(OR = 0. 854, 95%CI: 0.816–0.894, P = 1.844E-11). However, the other nine lipid-lowering drug targets had no significant effect on AF. Notably, we found a mediator role of Fibroblast Growth Factor 5 (FGF5) in the protective effect of LPL agonist on AF with a mediator ratio of 9.22%. Sensitivity analyses supported the robustness of our findings, indicating a possible mediating pathway by which LPL agonists affect the risk of AF.ConclusionOur study provides new insights into the complex interactions among lipid-lowering agents, circulating inflammatory factors and AF, and also identified a potential mediating role of FGF5 in the pathogenesis of AF. Our findings highlight the potential of LPL agonists and targeting specific inflammatory factors for therapeutic intervention in AF, providing promising avenues for future research and clinical strategies for the management and prevention of AF.
The neo-aortic valve in patients with hypoplastic left heart syndrome is largely preserved: a serial follow-up CMR study
Authors: Burleigh Abigail , Gabbert Dominik Daniel , Ide Yujiro , Voges Inga 
Published: November 2024

BackgroundIn hypoplastic left heart syndrome (HLHS) patients, neo-aortic valve regurgitation can negatively impact right ventricular (RV) function. We assessed neo-aortic valve function and RV volumetric parameters by analysing serial cardiovascular magnetic resonance (CMR) studies in HLHS patients after completion of total cavopulmonary connection (TCPC).MethodsConsecutive CMR examinations of 80 patients (female: 22) with two (n = 80) or three (n = 45) examinations each were retrospectively analysed. RV volumetry was performed using short-axis cine images. RV end-diastolic and end-systolic volumes normalised to body surface area (BSA, RVEDVi, RVESVi), ejection fraction (RVEF) and stroke volume (RVSV) were measured. Neo-aortic flow, regurgitant fraction (RF) and peak velocity were quantified from phase-contrast cine images.ResultsMedian neo-aortic regurgitation was mild at all three examinations (RF &lt;20%) and there was no significant increase in RF over time (p &gt; 0.05). None of the patients had significant neo-aortic valve stenosis (peak velocity &gt;3 m/s). RF correlated with RVESVi and RVEF at the second examination. At the third examination, RF correlated with RVESVi and RVEDVi even in patients with RF &lt;15% (RVESVi: r = 0.40, p = 0.001; RVEDVi: r = 0.34, p = 0.031).ConclusionAssessment of serial CMR studies in HLHS patients after TCPC completion demonstrates a preserved neo-aortic valve function. Nevertheless, thorough follow-up is mandatory as even mild neo-aortic dysfunction might impact RV size and function over a longer term.
Cybermycelium: a reference architecture for domain-driven distributed big data systems
Authors: Ataei Pouya 
Published: November 2024

IntroductionThe ubiquity of digital devices, the infrastructure of today, and the ever-increasing proliferation of digital products have dawned a new era, the era of big data (BD). This era began when the volume, variety, and velocity of data overwhelmed traditional systems that used to analyze and store that data. This precipitated a new class of software systems, namely, BD systems. Whereas BD systems provide a competitive advantage to businesses, many have failed to harness the power of them. It has been estimated that only 20% of companies have successfully implemented a BD project.MethodsThis study aims to facilitate BD system development by introducing Cybermycelium, a domain-driven decentralized BD reference architecture (RA). The artifact was developed following the guidelines of empirically grounded RAs and evaluated through implementation in a real-world scenario using the Architecture Tradeoff Analysis Method (ATAM).ResultsThe evaluation revealed that Cybermycelium successfully addressed key architectural qualities: performance (achieving &lt;1,000 ms response times), availability (through event brokers and circuit breaking), and modifiability (enabling rapid service deployment and configuration). The prototype demonstrated effective handling of data processing, scalability challenges, and domain-specific requirements in a large-scale international company setting.DiscussionThe results highlight important architectural trade-offs between event backbone implementation and service mesh design. While the domain-driven distributed approach improved scalability and maintainability compared to traditional monolithic architectures, it requires significant technical expertise for implementation. This contribution advances the field by providing a validated reference architecture that addresses the challenges of adopting BD in modern enterprises.
Classifying driver mutations of papillary thyroid carcinoma on whole slide image: an automated workflow applying deep convolutional neural network
Authors: Tsou Peiling , Wu Chang-Jiun 
Published: November 2024

BackgroundInformative biomarkers play a vital role in guiding clinical decisions regarding management of cancers. We have previously demonstrated the potential of a deep convolutional neural network (CNN) for predicting cancer driver gene mutations from expert-curated histopathologic images in papillary thyroid carcinomas (PTCs). Recognizing the importance of whole slide image (WSI) analysis for clinical application, we aimed to develop an automated image preprocessing workflow that uses WSI inputs to categorize PTCs based on driver mutations.MethodsHistopathology slides from The Cancer Genome Atlas (TCGA) repository were utilized for diagnostic purposes. These slides underwent an automated tile extraction and preprocessing pipeline to ensure analysis-ready quality. Next, the extracted image tiles were utilized to train a deep learning CNN model, specifically Google’s Inception v3, for the classification of PTCs. The model was trained to distinguish between different groups based on BRAFV600E or RAS mutations.ResultsThe newly developed pipeline performed equally well as the expert-curated image classifier. The best model achieved Area Under the Curve (AUC) values of 0.86 (ranging from 0.847 to 0.872) for validation and 0.865 (ranging from 0.854 to 0.876) for the final testing subsets. Notably, it accurately predicted 90% of tumors in the validation set and 84.2% in the final testing set. Furthermore, the performance of our new classifier showed a strong correlation with the expert-curated classifier (Spearman rho = 0.726, p = 5.28 e-08), and correlated with the molecular expression-based classifier, BRS (BRAF-RAS scores) (Spearman rho = 0.418, p = 1.92e-13).ConclusionsUtilizing WSIs, we implemented an automated workflow with deep CNN model that accurately classifies driver mutations in PTCs.
Monoclonal antibodies targeting type 2 inflammation in eosinophil-associated diseases during pregnancy: insights from two eosinophilic granulomatosis with polyangiitis cases and a comprehensive literature review
Authors: Davanzo Federica , Iorio Luca , Calligaro Antonia , Doria Andrea , Padoan Roberto 
Published: November 2024

BackgroundWith the widespread availability of monoclonal antibodies targeting type 2 inflammation, managing pregnancies in patients with eosinophil-associated diseases, including eosinophilic granulomatosis with polyangiitis (EGPA), has become a crucial issue.MethodsStarting from a two-case series of patients with EGPA, safely treated with anti-interleukin (IL)5/IL5R monoclonal antibodies during pregnancy, we conducted a comprehensive literature review to identify cases reporting the use of monoclonal antibodies for treating EGPA and other eosinophil-associated diseases in pregnant women.ResultsWe present two cases of patients with ANCA-negative EGPA. The first case involves a 35-year-old patient with benralizumab, resulting in successful disease control and a healthy pregnancy despite a history of miscarriage and gestational diabetes. The second case describes a 35-year-old woman who continued mepolizumab during pregnancy, leading to a healthy infant despite two prior early miscarriages. A literature review of 22 papers, covering 97 patients using biologics during pregnancy found no reports specific to EGPA but documented safe outcomes with monoclonal antibodies like mepolizumab, benralizumab, and dupilumab in other eosinophil-associated disorders. These biologics were effective in managing symptoms and reducing the need for oral glucocorticoids, with no observed teratogenic effects. However, complications such as gestational diabetes and preterm births were noted, particularly with dupilumab. No adverse events or pregnancy complications directly attributable to the biological therapy were reported.ConclusionsUncontrolled disease during pregnancy significantly threatens pregnancy viability, while the use of monoclonal antibodies effectively manages maternal disease, reduces glucocorticoid use, and helps prevent complications, even though more data are needed to establish risks and benefits.
Effects of integrated blood purification on haemodynamics and oxygen metabolism in children with severe sepsis
Authors: Ma Hekai , Wang Zhiyuan , Geng Jiahao , Zhao Junlin , Wang Tuanjie , Liu Ling , Xu Yuping , Liu Weiqing , Wang Min , Zhao Lan , Li Shujun 
Published: November 2024

ObjectiveTo investigate the effects of integrated blood purification on haemodynamics and oxygen metabolism in children with severe sepsis.MethodsClinical data of 12 children with severe sepsis admitted to the pediatric intensive care unit of our hospital between October 2021 and June 2022 were retrospectively analyzed. All patients were treated with integrated blood purification, and changes in haemodynamic parameters, including heart rate, blood pressure, mean arterial pressure and cardiac output, and oxygen metabolism parameters (blood lactic acid, oxygen delivery, oxygen consumption and oxygen extraction rate) were observed before and after treatment.ResultsThe heart rate (134[106,160] vs 111[101,128], p = 0.037), central venous pressure (9[7,10] vs 8[7,9], p = 0.04), stroke output (28[18,43] vs 21[15,31], p = 0.01), blood lactate (3.3[2,4] vs 2.5[1.3,3.6], p = 0.015), oxygen consumption (165.99[121.44,230.31] vs 124.18[82.51,162.86], p = 0.041) and oxygen extraction rate (38.83[31.87,44.62] vs 28.67[21.05,32.72], p = 0.019) were decreased, whereas systolic blood pressure (97[83,104] vs 107[94,116], p = 0.033) and central venous oxygen pressure (32[29, 37] vs 39[34,46], p = 0.005) were increased in the children after treatment compared with before treatment. There were no statistically significant differences in diastolic blood pressure, mean arterial pressure, cardiac output, arterial oxygen pressure and oxygen delivery before and after treatment (all p &gt; 0.05).ConclusionIntegrated blood purification can improve haemodynamic and oxygen metabolism parameters in children with severe sepsis, with a high value in clinical application.
Decoding the interplay of medical professionalism, mental well-being, and coping in undergraduate medical students across culture: using structural equation modeling
Authors: Sattar Kamran , Meo Sultan Ayoub , Yusoff Muhamad Saiful Bahri 
Published: November 2024

IntroductionThe rigorous nature of medical education, long and night shifts, and prevalent issues like stress, anxiety, and depression affect medical students’ mental well-being and medical professionalism. This study aims to explore the intricate relationships between mental well-being, medical professionalism, and coping strategies, among undergraduate medical students, utilizing structural equation modeling (SEM) to unravel these dynamics.MethodsConducted at Universiti Sains Malaysia, this cross-sectional study involved 234 medical students from the 1st, 3rd, and 5th years of the MBBS program. Data were collected via five validated survey instruments: DASS-9, TEQ, Dundee, Brief COPE, and CBI, through Google Forms. Participants were selected using purposive sampling. The surveys assessed mental well-being (burnout, anxiety, depression, stress), coping strategies, and medical professionalism attributes. Model fit was evaluated using established indices.ResultsFindings indicated that professional behavior reduces burnout and negatively impacts negative coping strategies (NCSs). Additionally, medical professionalism indirectly enhances empathy and positively influences CSs. Conversely, psychological distress increases NCSs and reduces empathy. Positive coping strategies (PCSs) enhance empathy levels, while MWB issues elevate NCSs.DiscussionThe study underscores the vital role of professional behavior in mitigating burnout and fostering positive coping mechanisms among medical students. Addressing MWB issues through targeted interventions can enhance empathy and professional behavior, ultimately improving the quality of patient care.
Association between the serum albumin–creatinine ratio and 28-day intensive care unit mortality among patients with sepsis: a multicenter retrospective cohort study
Authors: Lin Weiguo , Fu Cheng , Miao Jiangwei , Hong WeiLi , Chen Xinglin , Yan Shaorong , Lin Yuzhan 
Published: November 2024

IntroductionSepsis is a substantial global health challenge with a considerable disease burden. Despite advancements in sepsis research, the mortality rates associated with this condition remain high. The relationship between the serum albumin-to-creatinine ratio (sACR) and mortality in patients with sepsis remains unclear. Therefore, this study aimed to investigate the association between the sACR and 28-day mortality in intensive care unit (ICU) patients with sepsis.MethodsIn this retrospective cohort study, we used data sourced from the eICU Collaborative Research Database. The primary exposure variable was sACR, and the primary outcome measure was mortality within 28 days after ICU admission. Statistical analyses included univariate and multivariate logistic regression models, generalized additive models, and two-piecewise linear regression models, which were employed to explore non-linear relationships and threshold effects between sACR and mortality.ResultsThe study cohort comprised 9,690 ICU patients with sepsis, with a 28-day mortality rate of 9.99%. The results of the multivariate logistic regression model indicated that elevated sACR levels were significantly associated with a reduced risk of mortality (odds ratio = 0.78, 95% confidence interval: 0.71–0.87, p &lt; 0.001), even after adjusting for potential confounding variables. Curve fitting revealed a non-linear relationship between sACR and 28-day mortality, with an inflection point of 4.79.DiscussionThis study demonstrated that sACR is an independent risk factor for 28-day mortality in ICU patients with sepsis, exhibiting a non-linear negative dose–response relationship and a threshold effect. These findings may serve as early warning indicators in high-risk populations.
Association of serum klotho with cognitive function among individuals with nonalcoholic fatty liver disease
Authors: Wu Feilong , Pan Jie , Chen Mingtao , Lai Xuye , Gu Yingying , Pei Lei , Yang Lili 
Published: November 2024

IntroductionThis study investigated the potential link between serum klotho levels and cognitive function in patients with non-alcoholic fatty liver disease (NAFLD).Materials and MethodsUtilizing NHANES data from 2011 to 2014, the research included 356 eligible participants. NAFLD was identified with the United States Fatty Liver Index (US-FLI), and cognition was measured by various tests including the Animal Fluency Test (AFT), Digit Symbol Substitution Test (DSST), Immediate Recall Test (IRT), and Delayed Recall Test (DRT). Weighted logistic regression and restricted cubic splines were employed to analyze the relationship between klotho levels and cognitive scores.ResultsA significant nonlinear association was observed between klotho levels and the performance in DSST and Delayed Recall Test (DRT). After controlling for confounding factors, the study found a positive association between higher serum klotho levels and improved cognitive performance in both AFT and DSST. However, there was no significant relationship between klotho levels and the IRT or DRT, regardless of whether the natural logarithm or quartile was considered.DiscussionThe findings suggest that a higher serum klotho level may be positively correlated with better cognitive performance in NAFLD patients.
Efficacy and safety of drug-eluting stents versus bare-metal stents in symptomatic intracranial and vertebral artery stenosis: a meta-analysis
Authors: Zhang Yidan , Li Wenbin , Zhang Lei 
Published: November 2024

ObjectivesThis study aims to present the first comprehensive meta-analysis assessing the effectiveness and safety of drug-eluting stents (DES) versus bare-metal stents (BMS) in treating intracranial and vertebral artery stenosis.MethodsA comprehensive examination was undertaken to compare the effectiveness and safety of DES and BMS in individuals experiencing symptomatic stenosis in the intracranial and vertebral arteries through an in-depth analysis of clinical research. We conducted an extensive search across multiple databases including PubMed, Embase, Web of Science, and the Cochrane Library up to September 2024. The emphasis of our investigation was on various outcomes including rates of in-stent restenosis, symptomatic occurrences of in-stent restenosis, incidence of stroke, procedural success, mortality rates, complications associated with the procedure, and any adverse events.ResultsOur analysis included 12 studies with a total of 1,243 patients (562 in the DES group and 681 in the BMS group). The findings demonstrated a significantly lower rate of in-stent restenosis in the DES group for both intracranial [odds ratio (OR): 0.23; 95% confidence interval (CI): 0.13 to 0.41; p &lt; 0.00001] and vertebral artery stenosis (OR: 0.38; 95% CI: 0.20 to 0.72; p = 0.003) compared to the BMS group. Additionally, the DES group showed a significantly reduced rate of postoperative strokes in vertebral artery stenosis cases (OR: 0.38; 95% CI: 0.16 to 0.90; p = 0.03), with no significant differences noted in the intracranial artery stenosis comparison (OR: 0.63; 95% CI: 0.20 to 1.95; p = 0.42). The study also revealed no significant disparities in symptomatic in-stent restenosis, procedural success, mortality, adverse effects, and perioperative complications between the two groups across the conditions studied.ConclusionThe comparison indicates that DES significantly reduces the risk of in-stent restenosis and postoperative strokes in patients with vertebral artery stenosis, compared to BMS. For both intracranial and vertebral artery stenosis, DES and BMS exhibit comparable safety profiles.Systematic review registrationhttps://www.crd.york.ac.uk/PROSPERO/display_record.php?RecordID=439967.
Association of blood vitamin A with osteoarthritis: a nationally representative cross-sectional study
Authors: Wu Ao , Wu Ning-ning , Xu Peng-hui , Jin Yao , Yang Zhi-kai , Teng Jia-wen 
Published: November 2024

ObjectivesVitamin A plays an important role in health, especially regarding its impact on bone tissue. Vitamin A can lead to bone damage and deformity, thus becoming an important causative factor in osteoarthritis. In this study, we aimed to evaluate the association of serum vitamin A with osteoarthritis.MethodsWe included participants who self-reported whether they had OA in NHANES 2001–2006 and NHANES 2017–2018 to explore the association and dose–response relationship between vitamin A concentration and risk of osteoarthritis through weighted multivariate logistic models and restricted cubic splines. Sensitivity and stratification analyses were also used to assess the robustness of the results.ResultsA total of 18,034 participants were included in this study, and a linear association between serum vitamin A concentration and osteoarthritis risk was observed. The OR of osteoarthritis was 1.22 (95% CI: 0.98, 1.52), 1.40 (95% CI: 1.05,1.85), and 1.47 (95% CI: 1.14, 1.91) for participants in the second, third, and fourth quartiles, respectively, compared with the lowest vitamin A reference group. Similar results were obtained when sensitivity and stratification analyses were performed.ConclusionSerum vitamin A is positively associated with osteoarthritis risk. Within a certain range of vitamin A concentrations, vitamin A is a protective factor against osteoarthritis, beyond which it becomes a causative factor for osteoarthritis.
Evaluating nivolumab plus gemcitabine–cisplatin’s cost-effectiveness for aUC in China
Authors: Meng Kehui , Xiang Heng , Wu Meiyu , Xie Ouyang , Li Andong , Tan Chongqing , Wan Xiaomin 
Published: November 2024

AimsAssessing the cost-effectiveness of Nivolumab with Gemcitabine–Cisplatin for Advanced Urothelial Carcinoma (aUC) treatment from the perspective of Chinese payers.MethodsA Markov model assessed economic outcomes, estimating health outcomes in quality-adjusted life years (QALYs). One-way and probabilistic sensitivity analyses were conducted to assess the impact of uncertainties on the results.ResultsThe base-case analysis showed Nivolumab plus Gemcitabine–Cisplatin yielded 0.59 QALYs at an extra cost of $78,780.61, leading to an incremental cost-effectiveness ratios (ICER) of $133,526.46/QALY. One-way sensitivity analysis highlighted Nivolumab’s cost as the key factor, while probabilistic sensitivity analysis showed a 0% chance of cost-effectiveness for Nivolumab plus Gemcitabine–Cisplatin in aUC treatment.ConclusionNivolumab plus Gemcitabine–Cisplatin is not cost-effective in the treatment of aUC.