bluuebunny/crossref_metadata_2025_split huggingface dataset:
Circular RNA microarray expression profile and potential function of circDOCK1 in colorectal cancer
Authors: Zhang Guojing , Wu Xiaoyan , Fu Hongmin , Sun Daqing 
Published: February 2025

IntroductionEndoscopic tissue biopsy combined with histopathology is the gold standard for the diagnosis of colorectal cancer (CRC); however, the invasive nature of this procedure hinders its acceptance by patients. Therefore, there exists a critical need to identify novel markers facilitating early CRC detection and prognosis. Circular RNAs (circRNAs) hold promise as novel clinical diagnostic markers. This study aimed to investigate the impact of circDOCK1 on CRC metastasis and prognosis as well as its underlying molecular mechanisms.MethodsWe explored circRNA expression profiles in four pairs of CRC tissues and adjacent non-carcinoma tissues via microarray analysis. After Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG), and circRNA–miRNA network analyses, circDOCK1 was chosen for further investigation. We evaluated its clinical relevance in 80 CRC tissue pairs and adjacent controls, correlating circDOCK1 expression with clinical characteristics. Follow-up data from patient telephone interviews were analyzed for survival outcomes. Transfection efficiency was confirmed via qRT-PCR in HCT116 and SW480 colon cells, and the effects of circDOCK1 on cell proliferation, migration, and invasion were assessed.ResultsMicroarray data revealed 149 significantly differentially expressed circRNAs, including 71 upregulated and 78 downregulated circRNAs, in CRC tissues. CircDOCK1 exhibited elevated expression in patients with CRC and emerged as an independent prognostic factor. Kaplan–Meier curve analysis suggested that circDOCK1 expression is an unfavorable prognostic factor in patients with CRC. In vivo experiments revealed that circDOCK1 overexpression enhanced the proliferation, migration, and invasion of CRC cells, with consistent results upon circDOCK1 downregulation.ConclusionThese data indicate that circDOCK1 may play a role in promoting the proliferation, migration, and invasion of CRC cells, suggesting its potential as a CRC biomarker.
Enhancing the utility of polygenic scores in Alzheimer’s disease through systematic curation and annotation
Authors: Mwesigwa Savannah , Dai Yulin , Enduru Nitesh , Zhao Zhongming 
Published: February 2025

IntroductionPolygenic Scores (PGSs) assess cumulative genetic risk variants that contribute to the association with complex diseases like Alzheimer’s Disease (AD). The PGS Catalog is a valuable repository of PGSs of various complex diseases, but it lacks standardized annotations and harmonization, making the information difficult to integrate for a specific disease.MethodsIn this study, we curated 44 PGS datasets for AD from the PGS Catalog, categorized them into five methodological groups, and annotated 813,257 variants to nearby genes. We aligned the scores based on the “GWAS significant variants” (GWAS-SV) method with the GWAS Catalog and flagged redundant files and those with a “limited scope” due to insufficient external GWAS support. Using rank aggregation (RA), we prioritized consistently important variants and provided an R package, “PgsRankRnnotatR,” to automate this process.ResultsOf the six RA methods evaluated, “Dowdall” method was the most robust. Our refined dataset, enhanced by multiple RA options, is a valuable resource for AD researchers selecting PGSs or exploring AD-related genetic variants.DiscussionOur approach offers a framework for curating, harmonizing, and prioritizing PGS datasets, improving their usability for AD research. By integrating multiple RA methods and automating the process, we provide a flexible tool that enhances PGS selection and genetic variant exploration. This framework can be extended to other complex diseases or traits, facilitating broader applications in genetic risk assessment.
Prognostic value of systemic immune-inflammation index for patients undergoing radical prostatectomy: a systematic review and meta-analysis
Authors: Chen Zhan , Zhang Yao , Chen Wei 
Published: February 2025

ObjectiveThe prognostic value of the systemic immune-inflammation index (SII) for prostate cancer (PCa) patients receiving different treatments remains unclear. This research examined the relevance of SII in individuals undergoing radical prostatectomy (RP).MethodsPubMed, Embase, Web of Science, Cochrane, Wanfang, and China National Knowledge Infrastructure (CNKI) dat3 abases were used to search literature up to May 2024. The quality was evaluated with Newcastle-Ottawa Scale. Outcomes examined were associations between SII and overall survival (OS), biochemical recurrence-free survival (BFS), and cancer-specific survival (CSS). Pooled analysis, Egger’s test, and sensitivity analysis were conducted using Review Manager 5.4.1 and Stata 15.1. The GRADE system was employed to evaluate and grade the evidence for each outcome. Subgroup analyses were performed for outcomes with significant heterogeneity to evaluate the possible confounders, if data were sufficient.ResultsOut of 101 identified studies, eight studies involving 8,267 individuals were included. Patients with higher SII had shorter overall survival (HR: 1.89; 95% CI: 1.31-2.71; P = 0.0006), biochemical recurrence-free survival (HR: 1.55; 95% CI: 1.08-2.22; P = 0.02), and cancer-specific survival (HR: 3.63; 95% CI: 1.66-7.94; P = 0.001). The evidence for OS and CSS was rated very low-quality due to serious heterogeneity and/or imprecision. The prognostic value of SII for BFS was rated as low-quality evidence, given no serious risk observed. Subgroup analysis showed that, except for the subgroup aged &gt;65 years (HR: 3.70; 95%CI: 0.91, 15.06, P=0.07), the prognostic value of SII for OS was not significant, but the prognostic value of SII for OS in other subgroups was still significant.ConclusionsHigh SII was linked to shorter OS, BFS, and CSS in patients undergoing RP. However, the quality of the evidence provided by this study was low.Systematic Review Registrationhttps://www.crd.york.ac.uk/PROSPERO/, identifier CRD42024558431.
Phase I study of pembrolizumab in combination with ibrutinib for the treatment of unresectable or metastatic melanoma
Authors: Yao Yuan , Yan Yiyi , Suman Vera J. , Dietz Allan B. , Erskine Courtney L. , Dimou Anastasios , Markovic Svetomir N. , McWilliams Robert R. , Montane Heather N. , Block Matthew S. 
Published: February 2025

BackgroundImmune checkpoint inhibitors (ICIs) have been transformative in the treatment of patients with metastatic melanoma, but primary and secondary resistance to ICI treatment is common. One key mechanism for ICI resistance is the skewing of the immune response from a cytotoxic (Th1) to a chronic inflammatory (Th2) profile. The small molecule ibrutinib is a dual-target agent that inhibits Bruton’s Tyrosine Kinase (BTK) and Interleukin-2-inducible T-cell Kinase (ITK), a key regulator of Th2 immunity. Therefore, combining ibrutinib and pembrolizumab could potentially induce an increase in Th1 immune polarity in melanoma patients. We hypothesize that the combination would be well-tolerated and might result in clinical benefit for patients with metastatic melanoma. The primary aim of this phase I study was to evaluate the safety, tolerability, and determine the maximum tolerated dose (MTD) of ibrutinib in combination with pembrolizumab in patients with metastatic melanoma.MethodsA 3 + 3 phase I clinical trial was conducted in patients with unresectable Stage III or metastatic melanoma (stage IV) not amenable to local therapy. Pembrolizumab (200 mg/kg every 3 weeks) was combined with ibrutinib, administered orally at the dose assigned at the time of registration (140 mg daily, 280 mg daily, and 420 mg daily). Patients were treated until disease progression, intolerability, or patient decision to discontinue. Blood samples were collected after each cycle of treatment for immunophenotyping and Th1/Th2 polarity assessment based on immune response markers.ResultsBetween January 31, 2017 and January 9, 2023, 17 patients were enrolled. The MTD of ibrutinib in combination with pembrolizumab was determined to be 420 mg daily. The adverse events leading to discontinuation included: grade 4 ALT and AST increase (1 pt, DL0); grade 4 ALT increase with grade 3 AST increase (1 pt, DL1); and grade 3 hyponatremia, hypoxia, and maculo-papular rash (1 pt, DL1). Three of the 16 patients treated had objective responses (2 partial responses, 1 complete response) lasting over 8 months. The median progression-free survival was 3 months, and median and overall survival was 1.8 years. The combination treatment did not result in consistent increase in Th1 immune polarity.ConclusionIn conclusion, the maximum tolerated dose of ibrutinib in combination with pembrolizumab in patients with advanced or metastatic melanoma was established at 420 mg by mouth once daily. The combination was well-tolerated but did not result in a consistent increase in Th1 immune polarity; further investigation is needed to assess the relative clinical efficacy of this approach. (Funded by Pharmacyclics; ClinicalTrials.gov number: NCT03021460)Clinical trial registrationwww.clinicaltrials.gov, identifier NCT03021460.
Generation and characterization of chicken monocyte-derived dendritic cells
Authors: Ngantcha Tatchou Elie , Milcamps Romane , Oldenhove Guillaume , Lambrecht Bénédicte , Ingrao Fiona 
Published: February 2025

IntroductionDendritic cells (DCs) play a crucial role in orchestrating immune responses by bridging innate and adaptive immunity. In vitro generation of DCs from mouse and human tissues such as bone marrow and peripheral blood monocytes, has been widely used to study their immunological functions. In chicken, DCs have mainly been derived from bone marrow cell cultures, with limited characterization from blood monocytes.MethodsThe present study takes advantage of newly available chicken immunological tools to further characterize chicken monocyte-derived dendritic cells (MoDCs), focusing on their phenotype, and functions, including antigen capture and T-cell stimulation, and response to live Newcastle disease virus (NDV) stimulation.ResultsAdherent chicken PBMCs were cultured with recombinant chicken granulocyte-macrophage colony-stimulating factor (GM-CSF) and interleukin-4 (IL-4), for 5 days, leading to the upregulation of putative CD11c and MHCII, markers of DC differentiation. Subsequent stimulation with lipopolysaccharide (LPS) or 24 h triggered phenotypic maturation of MoDCs, characterized by the increased surface expression of MHCII and co-stimulatory molecules CD80 and CD40, and elevated IL-12p40 secretion. This maturation reduced endocytic capacity but enhanced the allogenic stimulatory activity of the chicken MoDCs. Upon NDV stimulation for 6 h, MoDCs upregulated antiviral pathways, including retinoic acid-inducible gene I (RIG-I)-like receptors (RLRs), melanoma differentiation-associated protein 5 (MDA5) and laboratory of genetics and physiology 2 (LGP2), alongside increased production of type I interferons (IFNs), and the pro-inflammatory cytokines tumor necrosis factor-α (TNF-α), IL-1β, and IL-6. However, these responses were downregulated after 24 hours.ConclusionThese findings provide a comprehensive characterization of chicken MoDCs and suggest their potential as a model for studying host-pathogen interactions.
Association between systemic inflammatory response index and glaucoma incidence from 2005 to 2008
Authors: Li Xiang , Sun Yi Qing , Zhong Xiao Dan , Zhang Zhi Jie , Tang Jia Feng , Luo Zhan Yang 
Published: February 2025

ObjectiveThis study aimed to investigate the association between the Systemic Inflammatory Response Index (SIRI) and glaucoma using data from the 2005–2008 National Health and Nutrition Examination Survey (NHANES).MethodsWe performed a cross-sectional analysis using data from NHANES (2005–2008). Among participants who underwent non-mydriatic retinal imaging and Frequency Doubling Technology (FDT) visual field testing, 4,514 were included after excluding those with missing key variable data. SIRI and other inflammatory indices, including the systemic immune-inflammation index (SII), platelet-to-lymphocyte ratio (PLR), and neutrophil-to-lymphocyte ratio (NLR), were calculated from blood samples. Logistic regression models were employed to assess the relationship between these indices and glaucoma, adjusting for demographic and health-related variables.ResultsA significant positive association was found between elevated log2SIRI levels and the prevalence of glaucoma (Model 3: OR 1.24, 95% CI 1.07–1.44, p &lt; 0.005). We performed an in-depth analysis of the Log2SIRI quartiles and found a significant association between Log2SIRI Q4 and the occurrence of glaucoma (Model 3: OR1.62, 95%CI 1.12–2.34, p = 0.011). This correlation was further validated using the area under the receiver operator characteristic curve (AUC) in Model 3(AUC = 0.674).ConclusionElevated SIRI levels are significantly associated with the prevalence of glaucoma, highlighting the potential role of systemic inflammation in glaucoma pathogenesis. SIRI may serve as a useful biomarker for identifying individuals at risk of glaucoma, facilitating early detection and targeted intervention strategies. Further research is needed to validate these findings and explore their clinical applications.
Profiling the diversity of the village chicken faecal microbiota using 16S rRNA gene and metagenomic sequencing data to reveal patterns of gut microbiome signatures
Authors: Nene Mxolisi , Kunene Nokuthula Winfred , Pierneef Rian , Hadebe Khanyisile 
Published: February 2025

IntroductionThe production environment of extensively raised village chickens necessitates their adaptability to low-resource systems. The gut microbiome plays a critical role in supporting this adaptability by influencing health and productivity. This study aimed to investigate the diversity and functional capacities of the faecal microbiome in village chickens from Limpopo and KwaZulu-Natal provinces of South Africa.MethodsUsing a combination of 16S rRNA gene sequencing and shotgun metagenomic sequencing technologies, we analysed 98 16S rRNA and 72 metagenomic datasets. Taxonomic profiles and functional gene annotations were derived, focusing on microbial diversity, antibiotic resistance genes (ARGs), and potential zoonotic pathogens.ResultsTaxonomic analysis showed that the predominant phyla in both provinces were Firmicutes, Bacteroidota, Proteobacteria, and Actinobacteria. At the genus level, Escherichia and Shigella were prevalent, with Escherichia coli and Shigella dysenteriae identified as major contributors to the gut microbiome. ARGs were identified, with MarA, PmrF, and AcrE detected in KwaZulu-Natal, and cpxA, mdtG, and TolA in Limpopo. These genes primarily mediate antibiotic efflux and alteration.DiscussionThe detection of zoonotic bacteria such as Escherichia coli and Streptococcus spp. highlights potential health risks to humans through the food chain, emphasizing the importance of improved household hygiene practices. This study underscores the role of the gut microbiome in village chicken health and adaptability, linking microbial diversity to production efficiency in low-resource settings. Targeted interventions and further research are crucial for mitigating zoonotic risks and enhancing sustainability in village chicken farming.
A bibliometric analysis of research on dementia comorbid with depression from 2005 to 2024
Authors: Li Xia , Su Wei , Cai Lili 
Published: February 2025

IntroductionWith the global rise in life expectancy, the incidence of dementia is increasing, often accompanied by depressive symptoms. Understanding the interplay between dementia and depression is crucial, as depression may not only co-occur with but also potentially exacerbate the progression of dementia. This study employs bibliometric analysis to map the global research landscape, identify prevailing themes, and discern future research directions.MethodsWe analyzed reviews and original research articles on dementia and depression extracted from the Web of Science Core Collection spanning from 2005 to 2024. Utilizing tools such as CiteSpace, VOSviewer, and an R-based bibliometric analysis package, we assessed trends in publication volume, citation frequency, contributing countries, leading institutions, predominant journals, influential authors, and emergent keywords.ResultsA total of 1972 publications were obtained, revealing a consistent increase in both the number of publications and their citation impact over the study period. The United States is the country with the most publications and the most extensive collaborations. The University of Toronto and the Journal of Alzheimer’s Disease were identified as key contributors to this field. This research area is currently focused on cognitive impairments, the role of gut microbiota, and non-drug interventions. Future directions emphasize the importance of early detection and intervention, a deeper understanding of the gut-brain axis, and the integration of technology in treatment strategies. Additionally, there is a growing interest in the physiological and psychological interplays such as oxidative stress and its implications.ConclusionThis study underscores pathogenesis, comorbid conditions, and non-drug interventions as primary research focal points, suggesting these areas as potential pathways for therapeutic innovation. These insights are intended to deepen our understanding, enhance diagnostics, and improve the management of dementia and depression, providing guidance for future research aimed at addressing these escalating global health challenges.
Computational and in vitro evaluation of sumac-derived ©Rutan compounds towards Sars-CoV-2 Mpro inhibition
Authors: Kayumov Muzaffar , Marimuthu Parthiban , Razzokov Jamoliddin , Mukhamedov Nurkhodja , Asrorov Akmal , Berdiev Nodir S. , Ziyavitdinov Jamolitdin F. , Yashinov Ansor , Oshchepkova Yuliya , Salikhov Shavkat , Mirzaakhmedov Sharafitdin 
Published: February 2025

The emergence of the SARS-CoV-2 virus caused the COVID-19 outbreak leading to a global pandemic. Natural substances started being screened for their antiviral activity by computational and in-vitro techniques. Here, we evaluated the anti-SARS-CoV-2 main protease (Mpro) efficacy of ©Rutan, which contains five polyphenols (R5, R6, R7, R7’, and R8) extracted from sumac Rhus coriaria L. We obtained three fractions after large-scale purification: fraction 1 held R5, fraction 2 consisted of R6, R7 and R7’, and fraction 3 held R8. In vitro results showed their anti-Mpro potential: IC50 values of R5 and R8 made 42.52 µM and 5.48 µM, respectively. Further, we studied Mpro-polyphenol interactions by in silico analysis to understand mechanistic extrapolation of Rutan binding nature with Mpro. We extensively incorporated a series of in silico techniques. Initially, for the docking protocol validation, redocking of the co-crystal ligand GC-376* to the binding pocket of Mpro was carried out. The representative docked complexes were subjected to long-range 500 ns molecular dynamics simulations. The binding free energy (BFE in kcal/mol) of components were calculated as follows: R8 (−104.636) &gt; R6 (−93.754) &gt; R7’ (−92.113) &gt; R5 (−81.115) &gt; R7 (−67.243). In silico results of R5 and R8 correspond with their in vitro outcomes. Furthermore, the per-residue decomposition analysis showed C145, E166, and Q189 residues as the hotspot residues for components contributing to maximum BFE energies. All five components effectively interact with the catalytic pocket of Mpro and form stable complexes that allow the estimation of their inhibitory activity. Assay kit analyses revealed that Rutan and its components have effective anti-SARS-CoV-2 Mpro inhibitory activity.
The prevalence of and the effect of global stressors on eating disorders among medical students
Authors: Almahmeed Muneera B. , Almutawa Muna A. , Naguib Yahya M. 
Published: February 2025

BackgroundEating disorders (EDs) are among the most serious forms of psychiatric illness, potentially leading to multi-systemic complications. Owing to their high stress levels, medical students are more likely to experience mental health difficulties that predispose them to developing EDs. Societal stigmatization and misinformation, especially in a middle eastern context, contribute to the underreporting and challenges in seeking the appropriate treatment at an early stage, increasing the risk of complications and mortality. EDs remain an under-studied phenomena in the middle east, limiting understanding and treatment options.ObjectiveThe objectives of the current study were to assess the prevalence of EDs, potential contributing factors, and the impact of the COVID-19 pandemic as an independent global stressor among medical students at the Arabian Gulf University.MethodsThis cross-sectional study consisted of a three-part self-administered questionnaire comprising of demographic data, the Eating Attitudes-26 (EAT-26) test, and COVID-19 associated stressors. The study was conducted on medical students at the AGU in the preparatory year up to Year 6. Data was collected from September 2022 to February 2023.ResultsThree hundred and ninety-seven students were recruited in the present study. 32.1% of the tested students demonstrated an elevated risk for developing EDs. Living situation, earlier years of study, and mental health status were significantly associated with increased risk. Response to global stressors such as COVID-19 pandemic was significantly correlated to worsening EDs status in high-risk individuals.ConclusionEating disorders have been discovered to be highly prevalent among medical students, which brings to light an undervalued health concern. This warrants both awareness programs on campus, and the development of individual-tailored eating disorder treatment programs to halt progression and increase overall quality of life and education.
Beyond words: the relevance of autonomy-supportive language in university syllabi
Authors: Herrera Dora , Lira-Delcore Aranza , Lira Luttges Benjamín 
Published: February 2025

IntroductionUniversity syllabi are a semester-long working tool through which professors present a thematic content program, precise assessment mechanisms, and establish the activities schedule, among other tasks. Teachers can promote high-quality motivation among students through syllabi. The goal of this research was to replicate a previous study on the impact of syllabus language on student motivation.MethodsTwo studies were conducted. Study 1 aimed to examine, in 126 first- and second-year students in Humanities General Studies, how they perceive a syllabus with an autonomy-supportive “tone” vs. one with a controlling language. Study 2 explored, in 261 students, basic psychological needs (BPN) satisfaction and their affective approach to the course. Additionally, it investigated the type of motivation (autonomous vs. controlled) that students prioritize when selecting the course.ResultsFindings from Study 1 suggest that autonomy-supportive syllabi are perceived as more attractive, fair, and respectful from the student’s perspective. Results from Study 2 indicate that autonomy-supportive syllabi are related to a better perception of the course, greater BPN satisfaction, and autonomous motivation from students, increasing the probability of them choosing that subject.DiscussionIt is concluded that promoting autonomy, even through the written language shared between teachers and students, is important for improving teaching quality.