bluuebunny/crossref_metadata_2025_split huggingface dataset:
A novel molecular classification system based on the molecular feature score identifies patients sensitive to immune therapy and target therapy
Authors: Li Yang , Ding Yinan , Wang Jinghao , Wu Xiaoxia , Zhang Dinghu , Zhou Han , Zhang Pengfei , Shao Guoliang 
Published: November 2024

BackgroundHepatocellular carcinoma (HCC) is heterogeneous and refractory with multidimensional features. This study aims to investigate its molecular classifications based on multidimensional molecular features scores (FSs) and support classification-guided precision medicine.MethodsData of bulk RNA sequencing, single nucleotide variation, and single-cell RNA sequencing were collected. Feature scores (FSs) from hallmark pathways, regulatory cell death pathways, metabolism pathways, stemness index, immune scores, estimate scores, etc. were evaluated and screened. Then, the unsupervised clustering on the core FSs was performed and the characteristics of the resulting clusters were identified. Subsequently, machine learning algorithms were used to predict the classifications and prognoses. Additionally, the sensitivity to immune therapy and biological roles of classification-related prognostic genes were also evaluated.ResultsWe identified four clusters with distinct characteristics. C1 is characterized by high TP53 mutations, immune suppression, and metabolic downregulation, with notable responsiveness to anti-PD1 therapy. C2 exhibited high tumor purity and metabolic activity, moderate TP53 mutations, and cold immunity. C3 represented an early phase with the most favorable prognosis, lower stemness and tumor mutations, upregulated stroma, and hypermetabolism. C4 represented a late phase with the poorest prognosis, highest stemness, higher TP53 mutations, cold immunity, and metabolic downregulation. We further developed practical software for prediction with good performance in the external validation. Additionally, FTCD was identified as a classification-specific prognostic gene with tumor-suppressing role and potential as a therapeutic target, particularly for C1 and C4 patients.ConclusionsThe four-layer classification scheme enhances the understanding of HCC heterogeneity, and we also provide robust predictive software for predicting classifications and prognoses. Notably, C1 is more sensitive to anti-PD1 therapies and FTCD is a promising therapeutic target, particularly for C1 and C4. These findings provide new insights into classification-guided precision medicine.
DNA methylation patterns of circadian and ultradian genes are altered in the peripheral blood of patients with hidradenitis suppurativa
Authors: Radhakrishna Uppala , Ratnamala Uppala , Jhala Devendrasinh D. , Uppala Lavanya V. , Vedangi Aaren , Saiyed Nazia , Shah Sushma R. , Patel Maulikkumar , Rawal Rakesh M. , Mazza Tommaso , Jemec Gregor B. E. , Mazzoccoli Gianluigi , Damiani Giovanni 
Published: November 2024

BackgroundHidradenitis suppurativa (HS) is a chronic inflammatory skin condition that affects hair follicles in areas with apocrine sweat glands, such as the underarms, groin, and buttocks. The pathogenesis of HS is not fully understood, but considering the key role played by the biological clock in the control of immune/inflammatory processes the derangement of circadian and ultradian pathways could be hypothesized.MethodsWe analyzed genome-wide DNA methylation patterns in peripheral blood from 24 HS cases and 24 controls using the Infinium HumanMethylation450 BeadChip array (Illumina), followed by bioinformatics and statistical analyses.ResultsWe found that several circadian and ultradian genes were differentially methylated in HS patients, predominantly exhibiting hypomethylation. These genes were enriched in pathways such as MAPK and WNT cascades, acute phase response, cytokine release, inflammation, innate immune response, xenobiotic detoxification, and oxidative stress response.ConclusionAltered DNA methylation patterns of genes related to circadian and ultradian pathways could contribute to immune system derangement and inflammatory processes chronicization in addition to other comorbidities hallmarking HS onset and progression, at the same time representing possible druggable targets.
Exploring RPA1-ETAA1 axis via high-throughput data analysis: implications for PD-L1 nuclear translocation and tumor-immune dynamics in liver cancer
Authors: Qin Gaofeng , Chen Zengkuan , Tian Weihong , Chen Hongbo , Zhang Yu , Wei Wangzhi 
Published: November 2024

IntroductionETAA1 is recruited to DNA damage sites via its RPA -binding and ATR -activating domain (AAD) motifs, where RPA binding is crucial for ETAA1’s regulation of ATR activity. Methods &amp; resultsOur findings associate Programmed Death- Ligand1 (PD-L1) with the RPA1-ETAA1 axis, suggesting that upregulated RPA1 -dependent ETAA1 may facilitate PD-L1 nuclear accumulation. We observed strong correlations between ETAA1 and RPA1 with the components involved in HDAC2-mediated deacetylation, clathrin -dependent endocytosis, and PD-L1 nucleocytoplasmic shuttling, aligning with the established regulatory pathway of PD-L1 nuclear translocation. Moreover, nuclear PD-L1 transactivates a panel of pro-inflammatory and immune response transcription factors, potentially reshaping the tumor immune microenvironment. We identified a landscape of infiltrating lymphocytes influenced by ETAA1, finding that levels of ETAA1 were negatively correlated with CD8+ T and Natural Killer T (NKT) cells, but positively correlated with CD4+ T helper 2 (Th2) cells, cancer-associated fibroblasts (CAFs), myeloid-derived suppressor cells (MDSCs), neutrophils and regulatory T cells (Tregs), suggesting a potential role in immune evasion. Further analysis shows that the RPA1-ETAA1 axis is significantly associated with multiple metastasis mediators and unfavorable liver cancer progression, with higher expression observed in advanced stages and poorly differentiated subgroups. Discussion &amp; conclusionThese findings expand the role of the RPA1-ETAA1 axis beyond DNA repair, highlighting its potential as a target for cancer therapy.
Long non-coding RNA H19 as a prognostic biomarker for oral squamous cell carcinoma
Authors: Kumar Kiran , Hallikeri Kaveri , Oli Ajay Kumar , Radder Kiran , Jain Apoorva , Shilpasree A. S. , Dhanapal Raghu , Tabnjh Abedelmalek Kalefh , Selvaraj Siddharthan 
Published: November 2024

BackgroundH19, a 2.3 kb lncRNA, has been linked to tumor metastasis and progression, but its significance in oral squamous cell carcinoma (OSCC) remains unclear. H19 was initially thought to have a tumor-suppressive function, but recent studies have shown that it possesses both tumor-promoting and suppressive functions. The variation in H19 expression may be due to the influence of tobacco or low basal expression levels. However, there are limited studies available on the association between H19 and its role in the prognosis of OSCC.ObjectiveThe present study analyzes the expression of H19 correlated with clinicopathological parameters, tobacco habit, loco-regional recurrence, and overall survival.MethodsA longitudinal study was undertaken using 96 formalin-fixed paraffin-embedded (FFPE) OSCC tissues and 30 FFPE adjacent normal mucosa (NM) tissues from patients who had surgery between 2015 and 2018. The tissues were subjected to quantitative reverse-transcription PCR (qRT-PCR) to determine H19 expression. The differential expression levels of H19 in OSCC were compared to clinicopathological variables and risk habits using the t-test and ANOVA. H19 expression correlated overall survival was analyzed by drawing the Kaplan–Meier curve followed by the log-rank test. A multivariate Cox proportional hazards regression analysis was performed to determine the ability of H19 to independently predict loco-regional recurrence and overall survival for OSCC.ResultH19 was significantly underexpressed in OSCC compared to NM in both the study cases and the TCGA OSCC database. The lower expression of H19 was significantly associated with the tobacco smoking habit and was not associated with any clinical or pathological features. Multivariate Cox’s proportional hazards regression analysis indicated that low H19 expression and positive lymph node metastasis were independent predictors of overall survival for OSCC. Higher age, higher TNM staging, and low H19 expression were independent predictors of loco-regional recurrence.ConclusionThe findings in the present study indicate that H19 is a novel prognostic marker and may provide a therapeutic strategy for the targeted treatment of OSCC, and tobacco may play a role in the expression of H19.
Adherence to recommended diet among patients with diabetes mellitus type 2 on follow-up at Adama Hospital Medical College, Ethiopia
Authors: Abose Saron , Dassie Godana Arero , Megerso Abebe , Charkos Tesfaye Getachew 
Published: November 2024

IntroductionNon-adherence to dietary guidelines is a significant challenge in managing diabetes mellitus and its complications. Its consequences were significantly associated with a deterioration in patients’ quality of life and an increased socioeconomic burden on healthcare delivery systems. This study aimed to assess the magnitude of adherence to recommended diet and associated factors among patients with diabetes mellitus type 2 on follow-up care at Adama Hospital Medical College Oromia, Ethiopia.MethodsA hospital-based cross-sectional study design was conducted. Participants were selected through systematic random sampling. Data were collected using structured, interviewer-administered questionnaires. The perceived dietary adherence questionnaire was used to assess the level of dietary adherence. A simple binary logistic regression was used to identify candidate variables, while a multivariable logistic regression assessed factors associated with adherence to the recommended diet. A p-value &lt;0.05 were considered as statistically significant. All analyses were performed using SPSS and R programming software.ResultA total of 405 participants were included in the study, with a response rate of 96.2%. The magnitude of non-adherence to the recommended diet was 64.2% (95% confidence interval [CI]: 59.8, 68.6). In the multivariable logistic regression model, patients with low and middle income (AOR = 8.0; 95% CI: 3.4, 19.2) and (AOR = 2.75; 95% CI: 1.49, 5.55) respectively, high glycemic level (AOR = 2.15; 95% CI: 1.17, 3.94), food insecure (AOR = 12.7; 95% CI: 5.79, 28.2), poor diabetic knowledge (AOR = 2.88; 95% CI: 1.49, 5.55) and low perceived susceptibility (AOR = 2.97; 95% CI: 1.62, 5.45) were significantly associated factors for non-adherence to recommended diet among patients with diabetes mellitus type 2.ConclusionThis study revealed that approximately two-thirds of patients with type 2 diabetes mellitus experienced non-adherence to the recommended diet. Key factors linked to dietary non-adherence among T2DM patients include low to middle income, elevated glycemic levels, household food insecurity, limited diabetes knowledge, and low perceived susceptibility. An integrated approach that combines socioeconomic support, nutritional guidance, and risk awareness may greatly enhance dietary adherence and optimize diabetes management.
A multimodal travel route recommendation system leveraging visual Transformers and self-attention mechanisms
Authors: Juan Zhang , Zhang Jing , Gao Ming 
Published: November 2024

IntroductionWith the rapid development of the tourism industry, the demand for accurate and personalized travel route recommendations has significantly increased. However, traditional methods often fail to effectively integrate visual and sequential information, leading to recommendations that are both less accurate and less personalized.MethodsThis paper introduces SelfAM-Vtrans, a novel algorithm that leverages multimodal data—combining visual Transformers, LSTMs, and self-attention mechanisms—to enhance the accuracy and personalization of travel route recommendations. SelfAM-Vtrans integrates visual and sequential information by employing a visual Transformer to extract features from travel images, thereby capturing spatial relationships within them. Concurrently, a Long Short-Term Memory (LSTM) network encodes sequential data to capture the temporal dependencies within travel sequences. To effectively merge these two modalities, a self-attention mechanism fuses the visual features and sequential encodings, thoroughly accounting for their interdependencies. Based on this fused representation, a classification or regression model is trained using real travel datasets to recommend optimal travel routes.Results and discussionThe algorithm was rigorously evaluated through experiments conducted on real-world travel datasets, and its performance was benchmarked against other route recommendation methods. The results demonstrate that SelfAM-Vtrans significantly outperforms traditional approaches in terms of both recommendation accuracy and personalization. By comprehensively incorporating both visual and sequential data, this method offers travelers more tailored and precise route suggestions, thereby enriching the overall travel experience.
Sugary beverages intake and risk of chronic kidney disease: the mediating role of metabolic syndrome
Authors: Dai Xiao-Yu , Chen Xiang-Yu , Jia Li-Na , Jing Xiao-Tong , Pan Xiao-Yan , Zhang Xing-Yu , Jing Zhong , Yuan Jin-Qiu , He Qiang-Sheng , Yang Li-Ling 
Published: November 2024

BackgroundAlthough several studies linked the sugary beverages to chronic kidney disease (CKD), the role of different types of sugary beverages in the development of CKD remained inconsistent. This study aimed to examine the associations of sugar-sweetened beverages (SSBs), artificially-sweetened beverages (ASBs), and natural juices (NJs) with CKD risk, and assess the extent to which the associations were mediated through metabolic syndrome (MetS).MethodsThis is a prospective analysis of 191,956 participants from the UK Biobank. Participants with information on beverage consumption and no history of CKD at recruitment were included. Daily consumptions of SSBs, ASBs and NJs were measured via 24-h dietary recall. Cox models were fitted to calculate the hazard ratios (HRs) and confidence intervals (CIs) of sugary beverages intakes on CKD risk. The causal mediation analyses were conducted to investigate whether MetS explained the observed associations.ResultsWe documented 4,983 CKD cases over a median of 10.63 years follow-up. Higher consumption of SSBs and ASBs (&gt;1 units/d compared with none) was associated with an elevated risk of CKD (HR: 1.45; 95% CI: 1.30–1.61, P-trend &lt; 0.001 for SSBs and 1.52, 95% CI: 1.36–1.70 for ASBs). In contrast, we observed a J-shaped association between NJs and CKD with the with lowest risk at 0–1 unit/day (0–1 unit/d vs. 0, HR 0.86; 95% CI 0.81–0.91). The proportions of the observed association of higher intakes of SSBs and ASB with CKD mediated by MetS were 12.5 and 18.0%, respectively.ConclusionsHigher intakes of ASBs and SSBs were positively associated with the development of CKD, while moderate consumption of NJs was inversely associated with CKD risk. More intensified policy efforts are warranted to reduce intake of SSBs and ASBs for CKD prevention.
Elevated uric acid to serum albumin ratio: a predictor of short-term outcomes in Chinese heart failure patients
Authors: Liu Xianling , Chu Aihui , Ding Xiahao 
Published: November 2024

BackgroundThe prognostic value of the uric acid to albumin ratio (UAR) in heart failure (HF) remains underexplored. The objective of this research was to investigate the link between UAR and short-term outcomes in Chinese HF patients.MethodsWe analyzed data from 1893 HF patients, out of an initial cohort of 2008, who had available UAR measurements. The skewed distribution of UAR data was addressed by applying a Log-10 (lg) transformation and stratifying patients into three groups accordingly (low to high). The final outcome was identified as mortality or hospital readmission within 28 days. We employed restricted cubic spline analysis (RCS), Kaplan–Meier survival curves, and Cox proportional hazards models to evaluate the link between UAR and short-term outcomes.ResultsAmong 1893 patients with HF [≥ 70 years, 1,382 (73.0%); female, 1,100 (58.1%)], the incidence of 28-day outcome was 8.6%. The RCS analysis suggested a positive relationship between lg(UAR) and 28-day outcomes, with no evidence of nonlinearity (p = 0.008). The cumulative incidence of 28-day readmission/death indicated that patients in the tertile 3 faced a significantly elevated risk of adverse outcomes (p &lt; 0.001). Cox proportional hazards models showed that an elevated UAR was associated with a greater likelihood of 28-day mortality or hospital readmission (HR = 2.433, 95% CI: 1.638–3.615, p &lt; 0.001). Even after accounting for possible confounding variables, the result still existed (HR = 1.594, 95% CI: 1.032–2.462, p = 0.036). Moreover, the associations were consistent in various subgroups, and sensitivity analysis (all p &gt; 0.05).ConclusionIncreased UAR correlates with a heightened risk of short-term death or hospital readmission in Chinese individuals suffering from HF. Maintaining a relatively lower UAR could potentially improve the clinical prognosis for these patients.
Case report: A rare low-grade fumarate hydratase-deficient renal cell carcinoma
Authors: Sun Di , Hu Baohong , Li Xinna , Yang Ping , Yu Guohua 
Published: November 2024

AimTo study and analyze the clinicopathological features of low-grade fumarate hydratase-deficient renal cell carcinoma in order to improve the understanding of the diagnosis and management of rare and specific morphological cases of this tumor.MethodsA case of low-grade FH-deficient renal cell carcinoma in a male is reported, and its clinicopathological features were analyzed and literature review was performed.ResultsA 48-year-old middle-aged male with no relevant positive clinical signs was admitted to the hospital with an incidental finding of a mass in the lower pole of the left kidney during abdominal CT examination. Pathomorphology showed that the tumor cells were arranged in a variety of structures and the cells were low grade eosinophilic. Immunohistochemistry showed Pax-8 (+), Vim (partially +), FH (-), CK7 (-), CD117 (-), P504s (partially +), CD10 (partially +), CA-9 (-), TFE3 (partially +), SDHB (+), CK20 (-), and Ki-67 (+, about 2%). Final pathologic diagnosis: FH-deficient renal cell carcinoma (low grade).ConclusionSingle pure low-grade FH-deficient renal cell carcinoma of the kidney is extremely rare, and the image structure of this tumor exhibits diverse manifestations, which needs to be differentiated from many renal tumors in clinicopathological diagnosis in order to prevent misdiagnosis.
A unique tripartite collision tumor of the esophagus: a case report and literature review
Authors: Luo Shuai , Tian Xiaoxue , Xu Ting , Wang Jinjing 
Published: November 2024

BackgroundThe coexistence of two or more distinct neoplasms within the same anatomical site characterizes collision tumors. While the presence of dual tumors is frequently observed in esophageal cases, the simultaneous occurrence of three distinct tumor types is extremely rare, posing significant challenges for pathological evaluation and diagnosis. Surgical resection remains the primary treatment, with generally favorable outcomes.Case presentationA 58-year-old male with a two-month history of progressively worsening dysphagia over the past 10 days underwent a gastrointestinal barium meal examination, which revealed an irregular filling defect measuring approximately 89×50 mm in the mid-thoracic esophagus. Subsequent gastroscopic biopsy confirmed undifferentiated pleomorphic sarcoma in the mid-esophageal tissue. As the dysphagia advanced, a partial esophagectomy with lymph node dissection was performed. Postoperative pathology revealed a composite tumor consisting of adenoid cystic carcinoma, undifferentiated pleomorphic sarcoma, and focal squamous cell carcinoma. Squamous cell carcinoma metastasis was identified in one lymph node. No adjuvant therapies, such as chemotherapy, radiotherapy, targeted therapy, or immunotherapy, were administered following surgery. The patient had been under monitoring for 101 months, with no signs of recurrence or metastasis.ConclusionThis case represents the first documented instance of a tripartite collision tumor in the esophagus, composed of undifferentiated pleomorphic sarcoma, squamous cell carcinoma, and adenoid cystic carcinoma, with clear histological distinction. A thorough review of the literature was performed to summarize clinicopathological features. Surgical resection leads to a favorable prognosis. Tumors containing both carcinomatous and sarcomatous elements tend to have a more favorable prognosis compared to those composed entirely of carcinomatous tissue, providing valuable insights for future diagnostic and therapeutic strategies.
The diagnostic efficacy of seven autoantibodies in early detection of ground-glass nodular lung adenocarcinoma
Authors: Guo Hua , Zhao Wei , Li Chunsun , Wu Zhen , Yu Ling , Wang Miaoyu , Wei Yuanhui , Wang Zirui , Liu Shangshu , Yin Yue , Yang Zhen , Chen Liangan 
Published: November 2024

BackgroundPersistent ground-glass nodules (GGNs) carry a potential risk of malignancy, however, early diagnosis remained challenging. This study aimed to investigate the cut-off values of seven autoantibodies in patients with ground-glass nodules smaller than 3cm, and to construct machine learning models to assess the diagnostic value of these autoantibodies.MethodsIn this multi-center retrospective study, we collected peripheral blood specimens from a total of 698 patients. A total of 466 patients with ground-glass nodular lung adenocarcinoma no more than 3cm were identified as a case group based on pathological reports and imaging data, and control group (n=232) of patients consisted of 90 patients with benign nodules and 142 patients with health check-ups. Seven antibodies were quantified in the serum of all participants using enzyme-linked immunosorbent assay (ELISA), and the working characteristic curves of the subjects were plotted to determine the cut-off values of the seven autoantibodies related ground-glass nodular lung adenocarcinoma early. Subsequently, the patients were randomly divided into a training and test set at a 7:3 ratio. Eight machine-learning models were constructed to compare the diagnostic performances of multiple models. The model performances were evaluated using sensitivity, specificity, and the area under the curve (AUC).ResultsThe serum levels of the seven autoantibodies in case group were significantly higher than those in the control group (P &lt; 0.05). The combination of the seven autoantibodies demonstrated a significantly enhanced diagnostic efficacy in identifying ground-glass nodular lung adenocarcinoma early when compared to the diagnostic efficacy of the autoantibodies when used respectively. The combined diagnostic approach of the seven autoantibodies exhibited a sensitivity of 84.05%, specificity of 91.85%, and AUC of 0.8870, surpassing the performance of each autoantibody used individually. Furthermore, we determined that Sparrow Search Algorithm-XGBoost (SSA-XGBOOST) had the best diagnostic performance among the models (AUC=0.9265), with MAGEA1, P53, and PGP9.5 having significant feature weight proportions.ConclusionsOur research assessed the diagnostic performance of seven autoantibodies in patients with ground-glass nodules for benign-malignant distinction, and the nodules are all no more than 3cm especially. Our study set cut-off values for seven autoantibodies in identifying GGNs no more than 3cm and constructed a machine learning model for effective diagnosis. This provides a non-invasive and highly discriminative method for the evaluation of ground-glass nodules in high-risk patients.