bluuebunny/crossref_metadata_2025_split huggingface dataset:
Spatiotemporal composition and diversity of endophyte communities in Dracaena cambodiana on Hainan Island
Authors: Li Sipeng , Liu Yang , Yang Xin , Yang Yun , Peng Junxiang , Xu Yanhong , Wei Jianhe 
Published: February 2025

IntroductionDracaena cambodiana produces a red resin known as Dragon’s blood, which is used worldwide in traditional medicine and as a dye. The role of endophytes in the resin-formation process remains underexplored. Understanding the endophyte communities and their functional roles in resin production could enable the development of efficient induction techniques for resin production.MethodsIn this study, ITS and metagenomic sequencing analyzed endophyte communities’ characteristics and functional traits in different tissues and D. cambodiana across multiple wild populations on Hainan Island.ResultsWe identified distinct fungal genera that were dominant in different tissues. Following injury, we observed significant changes in the expression of endophytic fungal genes. These changes indicated that metabolic pathways associated with resin metabolism, sucrose metabolism, signal transduction, and phenylalanine metabolism were likely involved in resin formation. Additionally, several glycosylation gene families were upregulated in the post-injury endophytic communities, which suggests a role in flavonoid transport and the reduction of autotoxic effects.DiscussionOur results suggest that endophytes play a vital role in the resin-formation process of D. cambodiana. Isolating specific endophytes or using synthetic communities could potentially improve resin yields and avoid pathogenic fungi, ensuring safety. The findings from this study provide a theoretical basis for the development of high-efficiency resin induction techniques by targeting the dynamic changes in endophyte communities across tissues, regions, and resin formation stages.
Landscapes of the main components, metabolic and microbial signatures, and their correlations during stack “sweating” of Eucommiae Cortex
Authors: Wang Linfeng , Wu Mengxian , Gu Bingnan , Wang Erfeng , Wu Faliang , Yang Jiapeng , Guo Bing , Li Xingke , Zhang Pengpai 
Published: February 2025

Introduction“Sweating,” a key step in the processing and production of Eucommiae Cortex (EC), which plays a vital role in the formation of the medicinal quality of EC. However, the mechanism of the effect of this traditional treatment of herbs on the quality of herbs is still unclear.MethodsIn this study, high performance liquid chromatography (HPLC), UPLC/MS-based untargeted metabolomics and high-throughput sequencing were applied to investigate the dynamic changes of the main active ingredients, differential metabolites and bacterial communities in the process of “sweating” in EC. The samples were prepared by the traditional stacking “sweating” method, and the samples were collected once a day for five consecutive days.ResultsThe results showed that the contents of the main active constituents, geniposidic acid (GPA), chlorogenic acid (CA), rutin (AU), pinoresinol diglucoside (PD) and total flavonoids (TFS), increased significantly after steaming, followed by a slight decrease. Furthermore, 807 metabolites were identified as crucial factors contributing to the metabolic alterations induced by the “sweating” process. Microbial diversity analysis showed considerable changes in microbiota characteristics, and the main functional microorganisms before and after “sweating” of EC were Gluconobacter, unclassified_c_Gammaproteobacteria, Pseudomonas, Pantoea, Pedobacter, and Parecoccus, which were involved in the five metabolic pathways of other secondary metabolites leading to significant changes in alkaloids, amino acid related compounds, flavonoids, phenylpropanoids and terpenoids.DiscussionThe correlation network established between core bacterial communities, active ingredients, and metabolic pathways elucidates the microbial regulation of EC quality during sweating. These findings provide a scientific foundation for optimizing processing duration and advancing quality control strategies through targeted microbial community management.
The assessment of autonomic nervous function in patients with gastrointestinal malignancies and its relationship with clinical characteristics
Authors: Xiwen Zhang , Qiyun Feng , Chuqiao Li , Anqi Jiang , Zhenzhen Wu , Qiong Deng , Yu Peng , Chunlin Wang 
Published: February 2025

IntroductionThe gastrointestinal tract is the organ most extensively distributed by autonomic nerves, and researches have indicated a relationship between automatic nerves and the progression of gastrointestinal cancers. This study aimed to evaluate the autonomic nervous function in patients with gastrointestinal cancer and to explore its relationship with clinical characteristics.MethodsWe employed the Composite Autonomic Symptom Score 31 (COMPASS-31) questionnaire and cardiovascular autonomic reflex tests (CARTs) to evaluate autonomic nervous function, while also conducting a thorough analysis of clinical data.ResultsOur results showed that low white blood cell (WBC) count (OR = 0.461, 95% CI: 0.218–0.976, p = 0.043) and increased maximum tumor diameter (OR = 1.619, 95% CI: 1.025–2.555, p = 0.039) were risk factors for autonomic dysfunction according to the COMPASS-31 assessment. While hypertension (OR = 5.747, 95% CI: 1.186–27.862, p = 0.030) and elevated platelet-to-albumin ratio (PAR) (OR = 1.256, 95% CI: 1.025–1.540, p = 0.028) were identified as independent risk factors for autonomic dysfunction based on the CARTs results. Combining the findings from COMPASS-31 and CARTs revealed that older age (OR = 1.133, 95% CI: 1.015–1.264, p = 0.027) and vascular invasion (OR = 7.706, 95% CI: 1.391–42.684, p = 0.019) were also independent risk factors for autonomic dysfunction.ConclusionOur findings reveal that these specific factors related to gastrointestinal cancers significantly influence autonomic nervous function. It is essential to evaluate autonomic nervous function and its associated risk factors in patients with gastrointestinal malignancies, which provide new insights into the intervention strategies for cancer diseases.
Association of probiotic supplementation and cardiovascular risk profiles of patients with coronary artery disease—a cross-sectional analysis of the NHANES database between 1999–2019
Authors: Palathinkara Murali , Aljadah Michael , Thorgerson Abigail , Dawson Aprill Z. , Widlansky Michael E. 
Published: February 2025

BackgroundAtherosclerotic cardiovascular disease (ASCVD) is a chronic inflammatory disease that leads to adverse events such as myocardial infarctions and stroke. Gut microbiome modulation is a promising target to reduce chronic inflammation and improve outcomes for patients with coronary artery disease (CAD). Risk profile patterns of CAD patients who target gut health with probiotics could provide insight into how gut modulation improves CAD clinical biomarkers. This study aims to evaluate the association between probiotic use and clinical markers of known atherosclerotic risk factors, in patients with CAD.MethodsWe conducted a cross-sectional large-database study using National Health and Nutrition Examination Survey (NHANES) data from years 1999–2020. The cohort included adults with at least a diagnosis of coronary heart disease, angina, and heart attack or two of the following: diabetes, high blood pressure, and high cholesterol. Analyses of clinical biomarkers compared probiotic to non-probiotic groups, between probiotic type groups, and between probiotic supplement strains.ResultsOur cohort included 14,992 survey responders. After weighting, this sample represented 46,217,980 US adults. There were 4,062,022 adults exposed to probiotics, 763,288 to probiotic supplements and 3,179,008 to probiotic foods. Probiotic exposure was associated with lower A1c (p &lt; 0.001), lower triglycerides (p &lt; 0.001), lower ASCVD risk score (p = 0.01) and higher HDL-C (p &lt; 0.001). Probiotic supplement exposure was associated with lower LDL-C (p = 0.003) and total cholesterol (p = 0.047).ConclusionOur study reinforces the beneficial association between probiotic ingestion and cardiovascular health in patients with existing atherosclerotic disease. Further studies to better determine potential mechanistic connections between the gut microbiota on cardiovascular risk factors is warranted.
Development and validation of a prognostic nomogram for patients with malignant peritoneal mesothelioma
Authors: Wang Xiaohan , Liu RuiTing , Wang Chunli , Sun Jingjing , Yang Dongliang 
Published: February 2025

BackgroundMalignant peritoneal mesothelioma(MPM) is a highly aggressive malignant tumor that originates from peritoneal mesothelial cells. Due to the rarity of MPM, there are few survival prediction models specifically for visualization of malignant peritoneal mesothelioma.ObjectiveThis study aimed to develop a nomogram for the overall survival of MPM based on the Surveillance, Epidemiology, and End Results (SEER) database and the data of Cangzhou People’s Hospital were used for external verification.MethodsPatients screened from the SEER database were divided into a training group and an internal verification group in a 7:3 ratio, with data from Cangzhou People’s Hospital used as the external verification group. Cox proportional hazard regression was utilized to identify significant factors, and nomograms for 6-month, 12-month, and 18-month overall survival were developed. The performance of the nomogram was assessed using consistency index, calibration curve, and K-M curve.ResultsAge, sex, histology, surgery, tumor size, chemotherapy, differentiated and the number of organ metastases were significant risk factors (p&lt;0.05) and were included in the nomogram.The area under the subject worker curve at 6,12,18 months overall survival (AUC) was 0.782,0.784,0.766 for the training group, 0.804,0.791,0.796 for the internal verification group, 0.767,0.749,0.783 for the external verification group. The predicted correction curve was in good agreement with the observed results. The Kaplan-Meier curves of different risk groups showed significant differences.ConclusionThis study represents the first visual prognostic model of MPM and the initial incorporation of organ metastasis into MPM prognostic factors. The nomograph serves as a reliable tool for clinicians to personalize overall survival prediction and maximize patient benefits by identifying the most effective treatment.
Development and validation of a prediction model for VTE risk in gastric and esophageal cancer patients
Authors: Zheng Xingyue , Wu Liuyun , Li Lian , Wang Yin , Yin Qinan , Han Lizhu , Wu Xingwei , Bian Yuan 
Published: February 2025

ObjectiveThis study focuses on the risk of venous thromboembolism (VTE) in patients with gastric or esophageal cancer (GC/EC), investigating the risk factors for VTE in this population. Utilizing machine learning techniques, the research aims to develop an interpretable VTE risk prediction model. The goal is to identify patients with gastric or esophageal cancer who are at high risk of VTE at an early stage in clinical practice, thereby enabling precise anticoagulant prophylaxis and thrombus management.MethodsThis study is a real-world investigation aimed at predicting VTE in patients with GC/EC. Data were collected from inpatients diagnosed with GC/EC at Sichuan Provincial People’s Hospital between 1 January 2018, and 31 June 2023. Using nine supervised learning algorithms, 576 prediction models were developed based on 56 available variables. Subsequently, a simplified modeling approach was employed using the top 12 feature variables from the best-performing model. The primary metric for assessing the predictive performance of the models was the area under the ROC curve (AUC). Additionally, the training data used to construct the best model in this study were employed to externally validate several existing assessment models, including the Padua, Caprini, Khorana, and COMPASS-CAT scores.ResultsA total of 3,742 cases of GC/EC patients were collected after excluding duplicate visit information. The study included 861 (23.0%) patients, of which 124 (14.4%) developed VTE. The top five models based on AUC for full-variable modeling are as follows: GBoost (0.9646), Logic Regression (0.9443), AdaBoost (0.9382), CatBoost (0.9354), XGBoost (0.8097). For simplified modeling, the models are: Simp-CatBoost (0.8811), Simp-GBoost (0.8771), Simp-Random Forest (0.8736), Simp-AdaBoost (0.8263), Simp-Logistic Regression (0.8090). After evaluating predictive performance and practicality, the Simp-GBoost model was determined as the best model for this study. External validation of the Padua score, Caprini score, Khorana score, and COMPASS-CAT score based on the training set of the Simp-GBoost model yielded AUCs of 0.4367, 0.2900, 0.5000, and 0.3633, respectively.ConclusionIn this study, we analyzed the risk factors of VTE in GC/EC patients, and constructed a well-performing VTE risk prediction model capable of accurately identifying the extent of VTE risk in patients. Four VTE prediction scoring systems were introduced to externally validate the dataset of this study. The results demonstrated that the VTE risk prediction model established in this study held greater clinical utility for patients with GC/EC. The Simp-GB model can provide intelligent assistance in the early clinical assessment of VTE risk in these patients.
Repurposing hydrochlorothiazide (HCTZ) for colorectal cancer: a retrospective and single center study
Authors: Foo Dominic Chi-Chung , Li Jiaxi , Huang Zheng , Sui Siming , Sin Ryan Wai-Yan , Man Abraham Tak Ka , Law Wai-Lun , Ng Lui 
Published: February 2025

BackgroundAnti-hypertensive drugs have been reported to demonstrate anti-inflammatory and anti-angiogenic effects. This study aims to investigate the association between anti-hypertensive drugs and the prognosis of colorectal cancer (CRC) patients.MethodsClinical data of 1134 CRC patients with hypertensions and the prescription of anti-hypertensive drugs who had undergone curative surgery in our hospital between 2005 and 2015 were retrieved. Their survival data and immune cell population in circulatory blood were compared among different types of anti-hypertensive drugs and overall CRC patients.ResultsThe 5-year overall survival for the antihypertensives-treated patients (65.2%) was higher than the CRC patients in Hong Kong (58.2%). Hydrochlorothiazide (HCTZ) group showed the best prognosis (79.1%) among different antihypertensive drug, particularly for advance stage or elderly patients, which are poor prognostic factors for overall CRC patients, demonstrated an obviously improved prognosis upon HCTZ treatment. Moreover, our data showed the recurrence rate was significantly lower for HCTZ group (18.3%) compared to non-HCTZ group (26.8%) and the reported rate (31%) of CRC patients in Hong Kong. Finally, patients with a lower pre-operative basophil level showed better overall and disease-free survival following HCTZ treatment.ConclusionThis study demonstrated the association of HCTZ treatment with a better prognosis of CRC patients.
Identification of glycolysis-related gene signatures for prognosis and therapeutic targeting in idiopathic pulmonary fibrosis
Authors: Gao Han , Sun Zhongyi , Hu Xingxing , Song Weiwei , Liu Yuan , Zou Menglin , Zhu Minghui , Cheng Zhenshun 
Published: February 2025

BackgroundGlycolysis plays a crucial role in fibrosis, but the specific genes involved in glycolysis in idiopathic pulmonary fibrosis (IPF) are not well understood.MethodsThree IPF gene expression datasets were obtained from the Gene Expression Omnibus (GEO), while glycolysis-related genes were retrieved from the Molecular Signatures Database (MsigDB). Differentially expressed glycolysis-related genes (DEGRGs) were identified using the “limma” R package. Diagnostic glycolysis-related genes (GRGs) were selected through least absolute shrinkage and selection operator (LASSO) regression regression and support vector machine-recursive feature elimination (SVM-RFE). A prognostic signature was developed using LASSO regression, and time-dependent receiver operating characteristic (ROC) curves were generated to evaluate predictive performance. Single-cell RNA sequencing (scRNA-seq) data were analyzed to examine GRG expression across various cell types. Immune infiltration analysis, Gene Set Enrichment Analysis (GSEA), and Gene Set Variation Analysis (GSVA) were performed to elucidate potential molecular mechanisms. A bleomycin (BLM)-induced pulmonary fibrosis mouse model was used for experimental validation via reverse transcription-quantitative polymerase chain reaction (RT-qPCR).Results14 GRGs (VCAN, MERTK, FBP2, TPBG, SDC1, AURKA, ARTN, PGP, PLOD2, PKLR, PFKM, DEPDC1, AGRN, CXCR4) were identified as diagnostic markers for IPF, with seven (ARTN, AURKA, DEPDC1, FBP2, MERTK, PFKM, SDC1) forming a prognostic model demonstrating predictive power (AUC: 0.831–0.793). scRNA-seq revealed cell-type-specific GRG expression, particularly in macrophages and fibroblasts. Immune infiltration analysis linked GRGs to imbalanced immune responses. Experimental validation in a bleomycin-induced fibrosis model confirmed the upregulation of GRGs (such as AURKA, CXCR4). Drug prediction identified inhibitors (such as Tozasertib for AURKA, Plerixafor for CXCR4) as potential therapeutic agents.ConclusionThis study identifies GRGs as potential prognostic biomarkers for IPF and highlights their role in modulating immune responses within the fibrotic lung microenvironment. Notably, AURKA, MERTK, and CXCR4 were associated with pathways linked to fibrosis progression and represent potential therapeutic targets. Our findings provide insights into metabolic reprogramming in IPF and suggest that targeting glycolysis-related pathways may offer novel pharmacological strategies for antifibrotic therapy.
Vulnerabilities in migrant live-in care arrangements for people with dementia: a comparative analysis of experts’ insights from Germany and Israel
Authors: Ulitsa Natalie , Nebowsky Anna Eva , Ayalon Liat , Schweda Mark , von Kutzleben Milena 
Published: February 2025

BackgroundThe global rise in dementia among older adults has led to an increased reliance on migrant live-in caregivers, particularly in countries like Germany and Israel. This triadic care arrangement, involving persons with dementia, their families, and migrant live-in caregivers, presents unique challenges and vulnerabilities. These vulnerabilities, deeply intertwined with ethical concerns, are shaped by the socio-cultural and legal contexts of each country. This study aims to explore these vulnerabilities through a comparative analysis of expert experiences in Germany and Israel.MethodA qualitative study was conducted using semi-structured interviews with 24 experts—14 from Israel and 10 from Germany—who have extensive experience in dementia care or migrant caregiving. The interviews were analyzed through qualitative content analysis, focusing on six dimensions of vulnerability: physical, psychological, relational/interpersonal, moral, socio-cultural-political-economic, and existential/spiritual.ResultsThe analysis revealed that all parties in the care triad—persons with dementia, migrant live-in caregivers, and family members—experience distinct yet interconnected vulnerabilities. These vulnerabilities are deeply entangled, manifesting in complex, interrelated ways both within each party and between the different parties in this triadic arrangement. The study also highlighted both similarities and differences in expert experiences between Germany and Israel, reflecting the unique socio-cultural and legal contexts of each country.ConclusionsThe study underscores the multifaceted and interdependent nature of vulnerabilities in migrant live-in care arrangements for people with dementia. By comparing expert insights from Israel and Germany, the research highlights the critical role of national policies and cultural contexts in shaping these vulnerabilities, leading to distinct experiences and challenges in each country. Addressing these vulnerabilities is essential for improving the quality of care and the well-being of all parties involved in the triadic care arrangement.
Healing hearts: mind-body therapy for mothers after stillbirth’s silent grief
Authors: Bar Vered , Hermesh Tamar , Reshef Piki , Hermetz Shoshy , Hertz-Palmor Nimrod , Gothelf Doron , Mosheva Mariela 
Published: February 2025

IntroductionApproximately 0.75% of pregnancies end with stillbirth, often leading to depression, anxiety, posttraumatic stress symptoms and suicidality. Knowledge regarding effective treatment options is lacking. In this retrospective cohort study we present a mind-body group therapy treatment protocol that was adapted for women and their partners who suffered stillbirth and report on its clinical effectiveness. Additionally, we identified demographic and clinical factors that were associated with clinical response.MethodsSixty-one women who coped with stillbirth were enrolled to a mind-body group therapy. Questionnaires assessing symptoms of depression, anxiety, and post-traumatic stress were administered to the women before and after the group intervention.ResultsAs expected, we found high rates of depression, state and trait anxiety and post-traumatic symptoms in our cohort before mind-body group therapy. At completion of treatment, the symptoms of depression, state anxiety, post-traumatic stress and suicidality significantly decreased. Improvement in symptoms of depression and post-trauma at follow-up was positively associated with severity of symptoms at baseline and with antidepressants treatment, and negatively associated with the number of children. Time since stillbirth was positively associated with the degree of improvement in posttraumatic symptoms only.ConclusionsOur findings suggest that mind-body group therapy may be associated with improvements in depression, post-traumatic stress symptoms, state anxiety, and suicidal ideation in women following stillbirth. Further research, including a control group is crucial for understanding of effective tools to treat this at-risk population.