bluuebunny/crossref_metadata_2025_split huggingface dataset:
Clinicopathological characteristics, evolution, and treatment outcomes of hormone receptor-negative/HER2-low metastatic breast cancer: a pooled analysis of individual patient data from three prospective clinical trials
Authors: Hu Shihui , Zhao Yannan , Xie Yizhao , You Shuhui , Hu Xichun , Zhang Jian , Wang Leiping , Cao Jun , Gong Chengcheng , Wang Biyun 
Published: November 2024

ObjectiveWith the approval of trastuzumab deruxtecan for the treatment of unresectable/metastatic HER2-low breast cancer, human epidermal growth factor receptor 2 (HER2)-low has emerged as a clinically actionable biomarker. There is an urgent need for a deeper understanding of HER2-low breast cancer patients. Therefore, this study was conducted to explore the clinicopathological characteristics, the evolution of HER2-low status, and its impact on the prognosis of hormone receptor (HoR)-negative/HER2-low metastatic breast cancer (MBC) patients.MethodsThis pooled analysis included 350 metastatic triple-negative breast cancer (mTNBC) patients who received first-line platinum-based chemotherapy at Fudan University Shanghai Cancer Center from November 2007 to July 2022. Patients were categorized into HER2-0 and HER2-low groups based on their HER2 status. Baseline clinicopathological characteristics, evolution of HER2 status between primary and metastatic lesions, and treatment efficacy were compared between the two groups.ResultsAmong the 350 mTNBC patients, 34.9% (122/350) were HER2-low and 65.1% (228/350) were HER2-0. Significant differences were observed between HER2-low and HER2-0 patients in terms of age and menopausal status. HER2-low patients were older (54 vs. 49 years, p=0.002) and had a lower proportion of premenopausal patients (32.8% vs. 52.6%, p&lt;0.001) compared to HER2-0 patients. No significant differences were observed in progression-free survival (PFS) and overall survival (OS) between HER2-low and HER2-0 patients receiving first-line platinum-based chemotherapy (mPFS: 7.43 vs. 8.30 months, p=0.389, HR=1.11, 95% CI 0.88-1.40; mOS: 25.37 vs. 26.63 months, p=0.907, HR=1.02, 95% CI 0.76-1.37). Additionally, 32.3% (41/127) of patients exhibited discordant HER2 status between primary and metastatic lesions, primarily evolving from HER2-0 to HER2-low. Notably, patients with discordant HER2 status had significantly longer PFS compared to those with concordant status (mPFS: 11.07 vs. 7.53 months, p=0.020). The Cox multivariate analysis showed that HER2 status consistency (p=0.026) was an independent predictor of PFS.ConclusionIn mTNBC patients, those with HER2-low status had similar responses to platinum-based chemotherapy as HER2-0 patients. There was significant discordance in HER2 status between primary and metastatic lesions. Patients with discordant HER2 status had better responses to platinum-based chemotherapy. Therefore, for patients with HER2-0 primary lesions, re-evaluation of HER2 status in metastatic lesions through biopsy may offer new treatment opportunities.
Mendelian randomization and bioinformatics unveil potential links between gut microbial genera and colorectal cancer
Authors: Wu Long , Wu Huan , Huang Fei , Mu Song , Li Xiao-Yun , Zhang Bao-Fang , Zhen Yun-Huan , Li Hai-Yang 
Published: November 2024

BackgroundColorectal cancer (CRC) poses a significant global health burden, with high incidence and mortality rates. Despite advances in diagnostic and therapeutic modalities, early diagnosis remains critical for improved outcomes. Recent research has realized the important role of gut microbiota in CRC development, highlighting the need to elucidate potential relationships.MethodsIn this study, we employed Mendelian randomization (MR) to establish a robust potential link between gut microbial genera and CRC. Data from the MiBioGen database provided curated genome-wide association study (GWAS) summary datasets for microbial genera, while the Finngen database provided CRC outcome data. Instrumental variables (IVs) were identified based on genetic variants associated with gut microbiota. Various MR methods, including Inverse Variance Weighted (IVW), Weighted Median, Weighted Mode, Simple Mode, and MR-Egger, were employed to estimate potential effects. Functional analysis of genes near single nucleotide polymorphisms (SNPs) was performed to unravel potential pathways.ResultsAnalysis of microbial genera identified five potentially associated with CRC: Eubacterium fissicatena group, Anaerofilum, Defluviitaleaceae UCG011, Ruminococcus 2, and Sutterella. Notably, Defluviitaleaceae UCG011 emerged as the only risk factor. Gene analysis revealed hub genes PTPRD and DSCAM near Defluviitaleaceae UCG011 associated SNPs. Expression analysis showed that PTPRD decreased in colon cancer and DSCAM decreased in rectal cancer. The methylation status of the PTPRD gene promoter region indicated potential regulatory alterations.ConclusionThis study establishes a potential relationship between five specific gut microbial genera, particularly Defluviitaleaceae UCG011, and CRC. Hub genes PTPRD and DSCAM provide insights into potential molecular mechanisms, suggesting the potential role of Defluviitaleaceae UCG011 in modulating the initiation and progression of CRC. Further research is essential to validate these associations and delve deeper into therapeutic implications.
Disrupted balance between pro-inflammatory lipid mediators and anti-inflammatory specialized pro-resolving mediators is linked to hyperinflammation in patients with alcoholic hepatitis
Authors: Li Wei , Xia Ying , Yang Jing , Sanyal Arun J. , Shah Vijay H. , Chalasani Naga P. , Yu Qigui 
Published: November 2024

BackgroundAlcoholic hepatitis (AH) is characterized by intense systemic and liver inflammation, posing significant risks of health complications and mortality. While inflammation is a crucial defense mechanism against injury and infection, its timely resolution is essential to prevent tissue damage and restore tissue homeostasis. The resolution of inflammation is primarily governed by specialized pro-resolving mediators (SPMs), lipid metabolites derived from w-6 and w-3 poly-unsaturated fatty acids (PUFAs). Currently, the balance between pro-inflammatory lipid mediators (PLMs) and SPMs in the w-6 and w-3 PUFA metabolic pathways and the impact of alcohol abstinence on profiles of PLMs and SPMs in AH patients are not well studied.MethodsIn this study, we used LC-MS/MS and ELISA to quantify levels of lipid mediators (LMs) and their precursors in the plasma samples from 58 AH patients, 29 heavy drinkers without overt liver diseases (HDCs), and 35 healthy controls (HCs). Subsequently, we assessed correlations of altered LMs with clinical parameters and inflammatory mediators. Furthermore, we conducted a longitudinal study to analyze the effects of alcohol abstinence on LMs over 6- and 12-month follow-ups.ResultsAH patients exhibited significantly higher plasma levels of w-6 PLMs (PGD2 and LTB4) and SPM RvE1 compared to HDCs or HCs. Conversely, the SPM LXA4 was significantly downregulated in AH patients. Some of these altered LMs were found to correlate with AH disease severity and various inflammatory cytokines. Particularly, the LTB4/LXA4 ratio was substantially elevated in AH patients relative to HDCs and HCs. This altered ratio displayed a positive correlation with the MELD score. Importantly, the majority of dysregulated LMs, particularly PLMs, were normalized following alcohol abstinence.
Identification of key biomarkers related to fibrocartilage chondrocytes for osteoarthritis based on bulk, single-cell transcriptomic data
Authors: Pan Bailin , Yao Peixiu , Ma Jinjin , Lin Xuanhao , Zhou Laixi , Lin Canzhen , Zhang Yufeng , Lin Bendan , Lin Chuangxin 
Published: November 2024

IntroductionOsteoarthritis (OA) is a prevalent joint disease that severely impacts patients’ quality of life. Due to its unclear pathogenesis and lack of effective therapeutic targets, discovering new biomarkers for OA is essential. Recently, the role of chondrocyte subpopulations in OA progression has gained significant attention, offering potential insights into the disease. This study aimed to explore the role of fibrocartilage chondrocytes (FC) in the progression of OA and identify key biomarkers related to FC.MethodsWe analyzed single-cell ribonucleic acid sequencing (scRNA-seq) data from samples of OA and normal cartilage, focusing on FC. Microarray data were integrated to identify differentially expressed genes (DEGs). We conducted functional-enrichment analyses, including Kyoto Encyclopedia of Genes and Genomes (KEGG) and Gene Ontology (GO), and used weighted gene co-expression network analysis (WGCNA) and the least absolute shrinkage and selection operator (LASSO) algorithm to select biomarkers. A novel risk model for OA was constructed using these biomarkers. We then built a transcription factor (TF)–gene interaction network and performed immunohistochemistry (IHC) to validate protein expression levels of these biomarkers in cartilage samples.ResultsThe study identified 545 marker genes associated with FC in OA. GO and KEGG analyses revealed their biological functions; microarray analysis identified 243 DEGs on which functional-enrichment analysis were conducted. Using WGCNA and LASSO, we identified six hub genes, on the basis of which we constructed a risk model for OA. In addition, correlation analysis revealed a close association between Forkhead Box (FoxO)-mediated transcription and these these biomarkers. IHC showed significantly lower protein levels of ABCA5, ABCA6 and SLC7A8 in OA samples than in normal samples.ConclusionThis study used a multi-omics approach to identify six FC-related OA biomarkers (BCL6, ABCA5, ABCA6, CITED2, NR1D1, and SLC7A8) and developed an exploratory risk model. Functional enrichment analysis revealed that the FoxO pathway may be linked to these markers, particularly implicating ABCA5 and ABCA6 in cholesterol homeostasis within chondrocytes. These findings highlight ABCA family members as novel contributors to OA pathogenesis and suggest new therapeutic targets.
Knowledge, attitude, and practice of psoriatic arthritis among patients with psoriasis
Authors: Mei Aihua , Luan Mei , Li Pan , Chen Jun , Mou Kuanhou 
Published: November 2024

IntroductionThis study aimed to investigate the knowledge, attitude and practice (KAP) of psoriatic arthritis among patients with psoriasis. The KAP questionnaire is a widely used tool in public health research, designed to assess individuals’ understanding (knowledge), beliefs (attitude), and behaviors (practice) related to a specific health condition.MethodsA cross-sectional study was conducted at Sinopharm Dongfeng General Hospital from September to November 2023. Demographic information and KAP scores were assessed using a structured questionnaire, which evaluated patient knowledge about psoriatic arthritis, their attitude toward managing it, and their practical engagement in preventive or treatment behaviors.ResultsIn this study, 392 valid questionnaires were analyzed. Of these, 290 respondents (74.0%) were male, and 296 (75.5%) reported no comorbid conditions. The median scores for knowledge, attitude, and practice were 8 (interquartile range [IQR]: 6–10), 21 (IQR: 19–24), and 14 (IQR: 8–22), respectively. Multivariate logistic regression analysis indicated that practice was independently associated with being female (OR = 0.426, 95% CI: 0.259–0.703, p = 0.001), being aged 30–39 years (OR = 2.159, 95% CI: 1.223–3.811, p = 0.008) or 40–49 years (OR = 2.002, 95% CI: 1.019–3.936, p = 0.044), having a Dermatology Life Quality Index (DLQI) score of 11–30 (OR = 2.569, 95% CI: 1.158–5.700, p = 0.020), and not having psoriatic arthritis (OR = 0.300, 95% CI: 0.168–0.537, p &lt; 0.001).ConclusionPatients with psoriasis had suboptimal knowledge, positive attitude and inactive practice toward psoriatic arthritis. To address this, healthcare providers should prioritize educational interventions, with a specific focus on younger patients, females, and individuals with a higher DLQI score, to enhance awareness and promote proactive management of psoriatic arthritis among this patient population.
Genetic association of type 2 diabetes and antidiabetic drug target with skin cancer
Authors: Zhao Juyan , Zhang Yu , Li Jianbo , Li Qi , Teng Ziyue 
Published: November 2024

BackgroundSeveral observational studies have suggested that type 2 diabetes (T2D) is a risk factor for skin cancer, and antidiabetic drugs may reduce skin cancer risk. Nevertheless, the findings remain ambiguous. This Mendelian randomization (MR) study aimed to investigate the causal association of T2D with skin cancer and evaluate the potential impact of antidiabetic drug targets on skin cancer.MethodsGenetic variants associated with glycated hemoglobin (HbA1c), Type 2 Diabetes (T2D), and antidiabetic drug targets (KCNJ11, ABCC8, PPARG, INSR, GLP1R, SLC5A2, and DPP4) were sourced from genome-wide association studies in the UK Biobank and the DIAMANTE consortium. Genetic summary statistics on skin cancer were obtained from the FinnGen consortium. MR analysis was primarily performed leveraging the inverse-variance weighted method, with additional sensitivity analyses conducted. Summary data-based MR (SMR) was utilized to further investigate the association between antidiabetic drug target gene expression and skin cancer. Colocalization analysis was carried out to verify the robustness of the results.ResultsGenetically proxied elevated levels of HbA1c were found to be suggestively associated with a reduced risk of melanoma (OR: 0.886, 95% confidence interval (CI): 0.792–0.991, p = 0.0347). Additionally, genetically proxied T2D was notably associated with a lower risk of basal cell carcinoma (OR: 0.960, 95% CI: 0.928–0.992, p = 0.0147). The study also discovered that perturbation of the antidiabetic drug target SLC5A2 was significantly associated with an increased risk of basal cell carcinoma (for SLC5A2 perturbation equivalent to a 6.75 mmol/mol decrement in HbA1c: OR: 2.004, 95% CI: 1.270–3.161, p = 0.0027). However, this finding was not supported by colocalization analysis. Notably, no other drug target perturbations were found to be associated with skin cancer. Furthermore, SMR analysis failed to detect an association between antidiabetic drug target genes and skin cancer.ConclusionThe study suggests that higher HbA1c levels and T2D may be associated with a reduced risk of skin cancer. However, the results did not provide evidence to support the association between antidiabetic drug targets and skin cancer. Further evaluation of these drug targets is required to confirm the findings in this analysis.
Prevalence of bronchiectasis in inflammatory bowel disease: a systematic review and meta-analysis
Authors: Ma Yu , Qiang Zhihui , Zhou Miaomiao , Zhang Tianyi , Li Zhuoyang , Zhong Haicheng , Chang Yue , Ning Zimeng , Liu Yun 
Published: November 2024

ObjectiveThe aim of this study was to conduct a systematic review and meta-analysis of the incidence of inflammatory bowel disease-associated bronchiectasis (IBD-BE) and to explore the possible risk factors for IBD-BE, which could help to understand the pulmonary involvement in patients with IBD and to determine the global incidence of the disease.MethodsWe searched PubMed and EMBASE databases to identify information on the prevalence of IBD-BE among IBD patients in the published literature. Information was extracted on study design, country, year, IBD-BE testing method, IBD characteristics, number of IBD-BE cases and total number of IBD patients, and factors associated with IBD-BE. We conducted meta-analyses using random-effects or fixed-effects models to estimate the prevalence of IBD-BE among IBD patients.ResultsOut of a total of 682 studies, we identified 16 studies that reported prevalence. These studies used a heterogeneous approach to identify IBD-BE. In these 16 studies, there were 92,191 patients with IBD, of whom 372 cases of IBD-BE were identified. The results of the meta-analysis showed that the overall prevalence of IBD-BE in IBD derived from the use of a random effects model was 5.0% (95% CI 2.0–12.0%). In contrast, the prevalence of IBD-BE in studies using high-resolution chest computed tomography (HRCT) imaging was 12% (95% CI 4–39%) using a random-effects model. When only retrospective studies with sample sizes greater than 100 (n = 6) were considered, the prevalence was 1% (95% CI 0–1%). However, when only retrospective studies with sample sizes less than 100 were included (n = 4), the prevalence was 29% (95% CI 6–100%); in prospective studies (n = 6), the combined prevalence was 11% (95% CI 4–29%). we performed a subgroup analysis of the differences in the incidence of IBD-BE between the different studies, each of which we subgrouped by type of study, type of disease, duration of disease, and diagnostic modality, and the results showed no significance. Future studies should standardize methods to identify IBD-BE cases and investigate the natural history and clinical course given the relatively high prevalence among IBD.ConclusionIn this systematic review and meta-analysis, the prevalence of IBD-BE was 12% among studies with HRCT imaging, suggesting that bronchiectasis may be an underestimated common extraintestinal manifestation of IBD. Asymptomatic patients with IBD-BE may present with abnormalities on HRCT or pulmonary function tests. Future studies should standardize methods to identify IBD-BE cases and investigate the natural history and clinical course given the relatively high prevalence among IBD.
Polymerization potential of a bacterial CotA-laccase for β-naphthol: enzyme structure and comprehensive polymer characterization
Authors: Refaat Marina , ElRakaiby Marwa T. , El Hariri El Nokab Mustapha , Es Sayed Julien , Elshewy Ahmed , Sebakhy Khaled O. , Moneib Nayera , Wang Tuo , Smith Thomas J. , Habib Mohamed H. 
Published: November 2024

IntroductionLaccases are blue-multicopper containing enzymes that are known to play a role in the bioconversion of recalcitrant compounds. Their role in free radical polymerization of aromatic compounds for their valorization remains underexplored. In this study, we used a pBAD plasmid containing a previously characterized CotA laccase gene (abbreviated as Bli-Lacc) from Bacillus licheniformis strain ATCC 9945a to express this enzyme and explore its biotransformation/polymerization potential on β-naphthol.MethodsThe protein was expressed from TOP10 cells of Escherichia coli after successful transformation of the plasmid. Immobilized metal affinity chromatography (IMAC) was used to generate pure protein. The biocatalytic polymerization reaction was optimized based on temperature, pH and starting enzyme concentration. 1H and 13C solution nuclear magnetic resonance (NMR), Fourier transform infrared spectroscopy (FTIR), and solid-state NMR (ssNMR) were used to characterize the formed polymer. A one-gram conversion reaction was done to explore applicability of the reaction in a pilot-scale.ResultsThe polymerization reaction generated a brown precipitate, and its chemical structure was confirmed using 1H and 13C NMR and FTIR. SsNMR revealed the presence of two different orientational hydroxyl functional groups in the polymer in addition to the presence of a very small amount of ether linkages (&lt; 2%). This analysis elucidated that polymerization occurred mainly on the carbons of the aromatic rings, rather than on the carbons attached to the hydroxyl groups, resulting in a condensed ring or polynuclear aromatic structure. The reaction was optimized, and the highest yield was attained under conditions of 37°C, pH 10 and a starting enzyme concentration of 440 nM in 50 mM phosphate buffer. A one-gram conversion yielded 216 mg of polymer as dry mass. The crystal structure of the enzyme was solved at 2.7 Å resolution using X-ray crystallography and presented with a hexagonal space group. The final structure was deposited in the Protein Databank (PDB) with an ID−9BD5.DiscussionThis article provides a green/enzymatic pathway for the remediation of phenolics and their valorization into potential useful polymeric materials. The comprehensive analysis of the formed polymer provides insight into its structure and functional moieties present. Based on the yield of the one-gram conversion, this synthetic method proves useful for a pilot-scale production level and opens opportunities to invest in using this polymer for industrial/environmental applications.
Risk factors analysis of cognitive frailty among geriatric adults in nursing homes based on logistic regression and decision tree modeling
Authors: Gao Jing , Bai Dingxi , Chen Huan , Chen Xinyu , Luo Huan , Ji Wenting , Hou Chaoming 
Published: November 2024

ObjectiveTo investigate the risk factors associated with cognitive frailty among older adults in nursing homes using logistic regression and decision tree modeling, and to compare the predictive performance of these methods.MethodsA cross-sectional study was conducted involving 697 participants aged 60 and older residing in eight nursing homes in Sichuan province, China. Participants were recruited using convenience sampling. Data were collected through questionnaires administered to the older adults. Logistic regression and decision tree modeling were employed to construct models predicting cognitive frailty.ResultsLogistic regression analysis identified age, education degree, exercise, intellectual activities, number of chronic diseases, nutritional status, sleep quality, and depression as significant predictors of cognitive frailty (all p &lt; 0.05). The final decision tree model consisted of three layers and 17 nodes. Six factors were identified as significant predictors: sleep quality, number of chronic diseases, depression, education level, nutrition, and exercise. Receiver operating characteristic (ROC) curve analysis revealed that the area under the curve (AUC) for the logistic regression model was 0.735 (95% CI: 0.701–0.767) with a sensitivity of 0.58 and specificity of 0.75. The AUC for the decision tree model was 0.746 (95% CI: 0.712–0.778) with a sensitivity of 0.68 and specificity of 0.70.ConclusionAge, education level, exercise, intellectual activities, sleep quality, number of chronic diseases, nutritional status, and depression are significant risk factors for cognitive frailty in older adults residing in nursing homes. Both logistic regression and decision tree models demonstrated comparable predictive performance, with each offering distinct advantages. The combined use of these methods can enhance predictive accuracy and provide valuable insights for clinical practice and policy development.
Dietary niacin intake and mortality among chronic kidney disease patients
Authors: Zhou Zhengxi , Yao Xiaotian 
Published: November 2024

BackgroundThe relationship between niacin and the risk of mortality in chronic kidney disease (CKD) patients remains unclear. This study aims to investigate the potential correlation.MethodsThis cohort study utilized data from the 2003–2018 National Health and Nutrition Examination Survey (NHANES). The study included 6,110 patients with CKD aged 18 years or older. Weighted Cox proportional hazards models and restricted cubic splines (RCS) were employed to estimate hazard ratios for all-cause mortality and cardiovascular disease (CVD) mortality. Niacin intake was estimated using the 24 h dietary recall method, based on the type and amount of food consumed. All-cause mortality and cardiac mortality rates were determined using National Death Index (NDI) mortality data (as of 31 December 2018).ResultsThe median niacin intake was 20.89 mg/day, with an interquartile range of 15.67–27.99 mg/day. During the follow-up period (median of 87 months), there were 1,984 all-cause deaths, including 714 CVD deaths. Compared with low niacin intake, the multivariate-adjusted hazard ratio for dietary intake of 22 mg or higher was 0.71 (95% CI, 0.57–0.88) for all-cause mortality and 0.75 (95% CI, 0.57, 0.98) for CVD mortality.ConclusionDietary niacin intake is associated with a reduction in all-cause and cardiac mortality among CKD patients.