bluuebunny/crossref_metadata_2025_split huggingface dataset:
Combining single-cell analysis and molecular docking techniques to construct a prognostic model for colon adenocarcinoma and uncovering inhibin subunit βb as a novel therapeutic target
Authors: Wu Qinqing , Ye Lu , Wu Yuwei , Zhao Mengyu , Lu Jiaxin , Yu Yanping , Niu Yixiao , Zhang Luxiao , Zuo Peijun 
Published: January 2025

BackgroundColon adenocarcinoma (COAD) is a malignancy with a high mortality rate and complex biological characteristics and heterogeneity, which poses challenges for clinical treatment. Anoikis is a type of programmed cell death that occurs when cells lose their attachment to the extracellular matrix (ECM), and it plays a crucial role in tumor metastasis. However, the specific biological link between anoikis and COAD, as well as its mechanisms in tumor progression, remains unclear, making it a potential new direction for therapeutic strategy research.MethodsWe employed transcriptomic data and clinical information from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) to pinpoint differentially expressed anoikis-related genes (ARGs) in COAD. Using Cox proportional hazards models and Lasso regression analysis, we developed a prognostic signature derived from these ARGs. We also investigated the roles and interactions of these genes in the tumor microenvironment by analyzing single-cell RNA sequencing data. Additionally, we employed molecular docking techniques to evaluate the potential of inhibin subunit beta B (INHBB) as therapeutic targets and to assess the binding affinity of candidate drugs. Finally, we used gene knockout techniques to silence the key gene INHBB and explored its biological functions in vitro.ResultsIn our study, by analyzing the expression differences of ARGs, we successfully classified patients with COAD. Kaplan-Meier survival analysis demonstrated that patients with elevated risk scores experienced poorer prognosis, a finding that was confirmed in both the training and validation cohorts. Additionally, immune infiltration analysis revealed a notable increase in immune cell presence within the tumor microenvironment of high-risk patients. Molecular docking identified potential drug candidates with high binding affinity to INHBB, including risperidone. Furthermore, in vitro experiments with INHBB showed that downregulation of its expression in COAD cell lines significantly reduced cellular viability and migration capacity.ConclusionIn summary, our research, based on the expression characteristics of ARGs, provides new insights into the precise classification, prognosis assessment, and identification of potential therapeutic targets in COAD. It also validates the key role of INHBB in the progression of COAD, establishing the foundation for future personalized treatment strategies.
Demographic features, clinical characteristics, and comorbid relation in hidradenitis suppurativa: a population-based study
Authors: Kaya Gökhan , Özgen Fatma Pelin , Kelahmetoğlu Osman , Su Küçük Özlem , Onsun Nahide 
Published: January 2025

Background/objectiveHidradenitis suppurativa (HS) is a chronic inflammatory disease affecting apocrine gland areas, characterized by painful nodules and abscesses that may result in sinus tracts and scarring. The global prevalence of HS is increasing due to heightened awareness, improved diagnostic methods, rising obesity rates, and higher smoking prevalence. This study aimed to describe the epidemiological, clinical, and comorbid characteristics of HS patients.MethodologyThis retrospective descriptive cross-sectional study included 193 outpatients aged between 15 and 73 years who visited a tertiary HS clinic between 2017 and 2022. Demographic, clinical, and comorbid characteristics were recorded and analyzed using chi-square and ordinal regression methods.ResultsThe mean age was 34.5 ± 12.1 years, with a mean disease duration of 5.9 ± 6.7 years. According to the Hurley classification, 61.1, 24.4, and 14.5% were stages I, II, and III, respectively. Comorbidities were present in 48.2% of patients, with psychiatric disorders (19.2%), diabetes mellitus (14%), and hypertension (9.3%) being most common. Disease duration, smoking, male gender, and atypical localization were associated with increased disease severity.ConclusionGeographic and cultural factors influence the prevalence, severity, and management of HS, necessitating tailored treatment. Effective management requires multidisciplinary screening for early detection and prevention of comorbidities, including psychiatric disorders, cardiovascular conditions, and metabolic syndrome.
Influential articles in autism and gut microbiota: bibliometric profile and research trends
Authors: Ying Jiangbo , Zhang Melvyn Weibin , Wei Ker-Chiah , Wong Sunny H. , Subramaniam Mythily 
Published: January 2025

ObjectiveAutism spectrum disorder (ASD) is a common neurodevelopmental disorder. Increasing evidence suggests that it is potentially related to gut microbiota, but no prior bibliometric analysis has been performed to explore the most influential works in the relationships between ASD and gut microbiota. In this study, we conducted an in-depth analysis of the most-cited articles in this field, aiming to provide insights to the existing body of research and guide future directions.MethodsA search strategy was constructed and conducted in the Web of Science database to identify the 100 most-cited papers in ASD and gut microbiota. The Biblioshiny package in R was used to analyze and visualize the relevant information, including citation counts, country distributions, authors, journals, and thematic analysis. Correlation and comparison analyses were performed using SPSS software.ResultsThe top 100 influential manuscripts were published between 2000 and 2021, with a total citation of 40,662. The average number of citations annually increased over the years and was significantly correlated to the year of publication (r = 0.481, p &lt; 0.01, Spearman’s rho test). The United States was involved in the highest number of publications (n = 42). The number of publications in the journal was not significantly related to the journal’s latest impact factor (r = 0.016, p &gt; 0.05, Spearman’s rho test). Co-occurrence network and thematic analysis identified several important areas, such as microbial metabolites of short-chain fatty acids and overlaps with irritable bowel syndrome.ConclusionThis bibliometric analysis provides the key information of the most influential studies in the area of ASD and gut microbiota, and suggests the hot topics and future directions. The findings of this study can serve as a valuable reference for researchers and policymakers, guiding the development and implementation of the scientific research strategies in this area.
Acupoint catgut embedding alleviates experimental autoimmune encephalomyelitis by modulating neuroinflammation and potentially inhibiting glia activation through JNK and ERK pathways
Authors: Liu Xiaofang , Yang Liansheng , Su Zhumin , Ma Xueying , Liu Yingying , Ma Lili , Ma Xiaomeng , Ma Mingxia , Liu Xiaoyun , Zhang Kun , Chen Xiaohong 
Published: January 2025

BackgroundAcupoint catgut embedding (ACE) is a traditional Chinese medicine technique commonly used for managing various disorders, including chronic inflammatory pain and allergic asthma. Despite its growing use, the neuroimmunological mechanisms underlying ACE treatment effects remain unclear.MethodsThis study investigated the roles and potential mechanisms of the effects of ACE in treating experimental autoimmune encephalomyelitis (EAE), a frequently used animal model of autoimmune neuroinflammation. The effects of ACE treatment were evaluated by monitoring body weight and EAE severity scores. Behavioral tests, histopathological analysis, ELISA, and flow cytometry were conducted to assess the therapeutic efficacy of ACE. RNA sequencing was performed to uncover ACE-associated transcriptional signatures in the spinal cords of EAE mice.ResultsThe results were validated through western blotting, qRT-PCR, and immunofluorescence (IF) staining. In ACE-treated mice, EAE disease severity was significantly ameliorated, along with improvements in anxiety-like behaviors and reduced inflammation and demyelination. The ACE treatment restored immune imbalance in the EAE mice by decreasing Th17 and Th1 cells, while increasing Treg cells in peripheral immune organs and reducing serum inflammatory cytokine levels. RNA sequencing revealed significant suppression of the genes and pathways associated with reactive microglial and astrocytic activation, corroborated by IF studies. Additionally, ACE treatment could suppress the ERK and JNK signaling pathways at both RNA and protein levels.ConclusionThese findings confirm the protective role of ACE in mitigating EAE symptoms by modulating microglial and astrocytic activity and regulating inflammatory cytokines.
Efficacy and safety of immunotherapy for head and neck squamous cell carcinoma: a meta-analysis of randomized clinical trials
Authors: Jiang Cailing , Wang Shuqin , Zhu Lijun 
Published: January 2025

BackgroundHead and neck squamous cell carcinoma (HNSCC) is one of the most common types of cancer worldwide and immune checkpoint inhibitors have shown favorable therapeutic effects in recurrent or metastatic or locally advanced head and neck squamous cell carcinoma (R/M/LA HNSCC). However, the effects of immunotherapy in HNSCC are still inconsistent because of complicating factors. This meta-analysis tries to provide a more precise assessment of the efficacy and safety of this integrated approach in HNSCC.MethodsWe conducted a systematic review and meta-analysis of randomized clinical trials according to Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) reporting guidelines. The outcomes were overall survival (OS), progression-free survival (PFS), and treatment-related adverse events (TRAEs). A total of 8 out of 2445 articles were analyzed, including 5067 HNSCC patients, including 823 and 4244 patients with LA HNSCC and R/M HNSCC.ResultsThe combined data revealed that immunotherapy has an apparent difference in OS (HR 0.86 95% CI 0.77-0.98) compared with standard of care (Soc, like fluoropyrimidine, methotrexate, docetaxel, or cetuximab) but was equal with the other treatment in PFS (HR 1.08, 95% CI 0.85-1.37). Furthermore, the occurrence of grade 3 or higher adverse events related to the drugs was lower than systematic therapy (OR 0.35, 95% CI 0.17-0.73).ConclusionsThe study has provided compelling evidence that immunotherapy is a significant benefit in OS for HNSCC patients, either R/M HNSCC or LA HNSCC, immunochemotherapy may benefit more for these patients, but double-agent immunotherapy showed no more benefit for R/M HNSCC patients.Systematic Review Registrationhttps://www.crd.york.ac.uk/, identifier CRD42023471570.
Repurposing the prostaglandin analogue treprostinil and the calcium-sensing receptor modulator cinacalcet to revive cord blood as an alternate source of hematopoietic stem and progenitor cells for transplantation
Authors: Prchal-Murphy Michaela , Zehenter Julia , Fischer Marlene , Pirabe Anita , Themanns Madeleine , Afrashteh Behnaz , Putz Eva Maria , Kollmann Karoline , Basílio José , Salzmann Manuel , Strohmaier Wolfgang , Krumpl Günther , Farr Alex , Sexl Veronika , Freissmuth Michael , Zebedin-Brandl Eva 
Published: January 2025

ObjectiveThe expanding field of hematopoietic cell transplantation (HCT) for non-malignant diseases, including those amenable to gene therapy or gene editing, faces challenges due to limited donor availability and the toxicity associated with cell collection methods. Umbilical cord blood (CB) represents a readily accessible source of hematopoietic stem and progenitor cells (HSPCs); however, the cell dose obtainable from a single cord blood unit is frequently insufficient. This limitation can be addressed by enhancing the potency of HSPCs, specifically their capacity to reconstitute hematopoiesis. In our study, we investigated the combined effects of treprostinil, a prostaglandin analog, and cinacalcet, a calcium-sensing receptor modulator, on the reconstitution of hematopoiesis.MethodsA Lineage Cell Depletion Kit was employed to isolate lineage-negative (lin−) HSPCs from mouse bone marrow. A Human CB CD34 Positive Selection Kit was utilized to isolate CD34+ cells from the CB of healthy donors. In vitro, the effects of treprostinil, cinacalcet, and their combination on the migration, adhesion, and differentiation of HSPCs were assessed. In vivo, homing and engraftment were examined. Eight-week-old female and male C57BL/6J, BALB/c, or female NSG mice served as recipient models.ResultsWhen administered concomitantly, treprostinil and cinacalcet exhibited mutual antagonism: the survival of recipient animals was lower when both drugs were administered together compared to either agent alone. Conversely, a sequential regimen involving priming with treprostinil/forskolin followed by cinacalcet treatment in vivo enhanced survival, irrespective of whether hematopoiesis was reconstituted by human or murine HSPCs. In vitro assays demonstrated enhanced migration and adhesion in response to the presence of treprostinil and cinacalcet, suggesting potential synergistic effects. Colony formation confirmed synergism.ConclusionAugmenting the bone marrow reconstitution potential of HSPCs with treprostinil and cinacalcet shows promise for rescuing patients undergoing HCT. This approach is particularly beneficial for those patients at high risk of transplant failure due to limited numbers of available HSPCs. Furthermore, enhancing the potency of HSPCs has the potential to alleviate the burden and risks associated with HSPC donation, as it would reduce the number of cells needed for collection.
Multi-omics approaches to deciphering complex pathological mechanisms of migraine: a systematic review
Authors: Liu Jiaojiao , Ren Qiaosheng , Du Boxuan , Liu Xian , An Yuqiu , Zhang Peichi , Li Lexi , Liu Zhenhong , Cao Kegang 
Published: January 2025

BackgroundMigraine represents a chronic neurological disorder characterized by high prevalence, substantial disability rates, and significant economic burden. Its pathogenesis is complex, and there is currently no cure. The rapid progress in multi-omics technologies has provided new tools to uncover the intricate pathological mechanisms underlying migraine. This systematic review aims to synthesize the findings of multi-omics studies on migraine to further elucidate the complex mechanisms of disease onset, thereby laying a scientific foundation for identifying new therapeutic targets.MethodsWe conducted a comprehensive systematic review, specifically focusing on clinical observational studies that investigate various aspects of migraine through the integration of genomics, transcriptomics, proteomics, and metabolomics. Our search encompassed multiple databases including PubMed, EMBASE, the Web of Science Core Collection, the Cochrane Library, China National Knowledge Infrastructure, the Chinese Science and Technology Periodical Database, the Wanfang database, and the China Biology Medicine Database to cover studies from database inception until 20 March 2024., The scope of our review included various aspects of migraine such as ictal and interictal phases; episodic or chronic migraine; menstrual-related migraine; and migraine with or without aura (PROSPERO registration number: CRD42024470268).ResultsA total of 38 studies were ultimately included, highlighting a range of genetic variations, transcriptional abnormalities, protein function alterations, and disruptions in metabolic pathways associated with migraine.These multi-omics findings underscore the pivotal roles played by mitochondrial dysfunction, inflammatory responses, and oxidative stress in the pathophysiology of migraine.ConclusionMulti-omics approaches provide novel perspectives and tools for comprehending the intricate pathophysiology of migraine, facilitating the identification of potential biomarkers and therapeutic targets.Systematic Review Registrationhttps://www.crd.york.ac.uk/PROSPERO/display_record.php?RecordID=470268, identifier CRD42024470268.
Safety assessment of tolvaptan: real-world adverse event analysis using the FAERS database
Authors: Cao Peiyang , Wang Qian , Wang Yan , Qiao Qing , Yan Liyuan 
Published: January 2025

ObjectiveThis study aims to analyze the adverse drug events (ADEs) associated with tolvaptan in the Food and Drug Administration Adverse Event Reporting System database from the fourth quarter of 2009 to the second quarter of 2024.MethodsAfter standardizing the data, various signal detection techniques, including Reporting Odds Ratio (ROR), Proportional Reporting Ratio (PRR), Bayesian Confidence Propagation Neural Network, and Multi-Item Gamma Poisson Shrinker, were employed for analysis.ResultsAmong the 7,486 ADE reports where tolvaptan was the primary suspected drug, a total of 196 preferred terms were identified, spanning 24 different system organ classes. Specifically, hepatobiliary disorders, renal and urinary disorders, and metabolic and nutritional disorders were found to be characteristic adverse reactions associated with tolvaptan. Additionally, uncommon but notable ADE signals were observed, such as renal cyst rupture, renal cyst infection, polycystic liver disease, and renal cyst hemorrhage. These several ADEs have not been referred to in the previous literature. Notably, strong ADE signals were detected for decreased urine osmolality [n = 5, ROR 149.74, PRR 149.7, IC (Information Component) 7.13, EBGM (Empirical Bayes Geometric Mean) 139.79], osmotic demyelination syndrome (n = 38, ROR 128.47, PRR 128.25, IC 6.92, EBGM 120.91), and pulmonary-related tumors such as bronchial metastatic carcinoma, bronchial carcinoma, metastatic small cell lung carcinoma, and small cell lung carcinoma. In the concomitant medication analysis of 7,486 suspected adverse drug reaction reports related to tolvaptan, the top three drugs most commonly used in combination with tolvaptan were furosemide, spironolactone, and amlodipine.ConclusionWhile tolvaptan provides therapeutic benefits, it poses a risk of significant adverse reactions. Clinicians should closely monitor the occurrence of events related to hepatobiliary disorders, renal and urinary disorders, metabolic and nutritional disorders, as well as benign, malignant, and indeterminate tumors during its clinical use.
Balancing act: optimizing blue light for melanogenesis while minimizing cellular damage in primary human skin cells
Authors: Barolet Augustin C. , Magne Brice , Ferland Karel , Uzunbajakava Natallia E. , Barolet Daniel , Germain Lucie 
Published: January 2025

IntroductionRecent findings show that visible light, particularly blue light, stimulates melanogenesis in human skin, though the underlying mechanisms remain debated. This study aimed to determine the cell damage threshold of non-ionizing blue light on keratinocytes while preserving their ability to stimulate melanogenesis.MethodsHuman keratinocytes (N = 3) and melanocytes (N = 3) were isolated from skin samples of varying Fitzpatrick skin phototypes and irradiated with blue light (λpeak = 457 nm) and UVA light (λpeak = 385 nm). Cellular metabolic activity was assessed using the AlamarBlue HS assay, α-Melanocyte-Stimulating Hormone (α-MSH) production by keratinocytes was quantified using ELISA, and Western blotting was used to assess pro-melanogenic factor expression in melanocytes.ResultsHigh blue light intensity (50 mW/cm2, 50 J/cm2) and UVA light (15 mW/cm2, 20 J/cm2) significantly reduced cellular metabolic activity, with a 0.86 ± 0.055 and 0.60 ± 0.031 (mean ± SD) fold decrease compared to their respective sham by day 7. In contrast, moderate blue light intensities (5–15 mW/cm2, 10–20 J/cm2) preserved cellular metabolic activity while stimulating α-MSH production, with an optimal balance achieved at 10 mW/cm2, 15 J/cm2 (1.14 ± 0.046 fold increase relative to sham on day 7). Co-culture experiments confirmed that irradiated keratinocytes enhanced melanogenesis in melanocytes via paracrine signaling, increasing the expression of Tyrosinase and Dopachrome Tautomerase (DCT). Direct blue light irradiation on melanocytes also increased pigmentation without significant cellular damage.DiscussionModerate-intensity blue light at 10 mW/cm2, 15 J/cm2 effectively stimulates melanogenesis while maintaining cellular metabolic activity in both keratinocytes and melanocytes, offering a promising, safe approach for blue light therapies targeting pigmentation disorders.
Association of parental rearing styles with suicidal ideation in Chinese adolescent patients with depression: a large-scale cross-sectional study
Authors: Liu Jiacheng , Cheng Chang , Edeleva Kamila , Zhao Zhen , Yang Liying , Kang Chuanyi , Wang Xiaohong , Zhao Na , Hu Jian 
Published: January 2025

BackgroundSuicide is the first cause of death among adolescents globally and has a severe impact on socioeconomic development. Several studies have found that suicide attempts and suicidal ideation (SI) are more likely to occur in adolescents with depression. Previous studies have found that stressful events in early childhood, especially family stress, can influence the occurrence of SI. Chinese parents tend to be more strict and less able to express their emotions, owing to unique national conditions, which may result in more parenting problems. Therefore, our study investigates the risk factors for SI in a large sample of Chinese adolescents with depression.MethodsA total of 1604 adolescent patients with depression were recruited in this study. A self-administered questionnaire collected the clinical and demographic data. SI was assessed by interview. The Egna Minnen Beträffande Uppfostran (EMBU) scale was used to evaluate parental rearing style.ResultsThe study showed that female (OR=1.886, 95%CI:1.502–2.368), sleep (OR=0.798, 95%CI:0.637–0.998), school management (OR=1.179, 95%CI:1.041–1.336), alcohol consumption (OR=1.798, 95%CI:1.304–2.479), child life (OR=1.797, 95%CI:1.457–2.216), maternal interference (OR=1.032, 95%CI:1.015–1.048), paternal emotional warmth (OR=0.975, 95%CI:0.966–0.983) and paternal rejection (OR=1.102, 95%CI:1.063–1.142) were significantly associated with SI.ConclusionsTo recognize SI earlier, physicians and nurses need to pay more attention to those female adolescent depression populations that are experiencing an unhappy childhood, non-democratic school management, alcohol consumption, excessive maternal interference, lack of paternal emotional warmth, and paternal rejection.