bluuebunny/crossref_metadata_2025_split huggingface dataset:
The U-shaped association of fasting plasma glucose to HbA1c ratio with mortality in diabetic and prediabetic populations: the mediating role of systemic immune-inflammation index
Authors: Yang Ming , Shangguan Qing , Xie Guobo , Sheng Guotai , Yang Jingqi 
Published: January 2025

BackgroundsThis study aimed to assess the association between fasting plasma glucose to glycated hemoglobin (FPG/HbA1c) ratio and mortality and to explore the mediating role of immunity and inflammation in diabetic and prediabetic populations.MethodsOur analysis included 10,267 participants with prediabetes or diabetes from the NHANES (1999-2018). The association between the FPG/HbA1c ratio and all-cause and cardiovascular(CVD) mortality was assessed using multivariate Cox proportional hazards models, restricted cubic splines(RCS), two-piecewise Cox proportional hazards models and sensitivity analysis. Mediation analysis was conducted to evaluate the systemic immune-inflammation index (SII) as a potential mediator.ResultsOver a median follow-up of 103 months, there were 535 CVD deaths and 1918 all-cause deaths. After multivariate adjustment, a U-shaped relationship was observed between the FPG/HbA1c ratio and both CVD and all-cause mortality, with threshold points at 1.080 and 1.013, respectively. Below the thresholds, the FPG/HbA1c ratio was negatively associated with CVD mortality (HR:0.200, 95% CI: 0.072, 0.559) and all-cause mortality(HR: 0.242, 95% CI: 0.118, 0.494). Above the thresholds, the ratio was positively associated with CVD mortality (HR=3.691, 95% CI: 2.011, 6.772) and all-cause mortality (HR=3.025, 95% CI: 2.279, 4.016). Mediation analysis revealed that SII mediated 19.02% of the association with CVD mortality and 8.86% with all-cause mortality (P &lt; 0.05).ConclusionsIn the prospective cohort, the FPG/HbA1c ratio demonstrated a U-shaped association with mortality in diabetic and prediabetic adults, with SII playing a significant mediating role. These findings suggest that interventions targeting immunity and inflammation may improve clinical outcomes in these populations.
Case report: Chemotherapy plus sintilimab for the treatment of gastroesophageal junction hepatoid adenocarcinoma with liver metastasis: a case study with literature review
Authors: Lu Genlin , Tu Jiarui , Tu Jinming , Jiang Renya 
Published: January 2025

ObjectiveTo elucidate the clinicopathological features and treatment of metastatic gastroesophageal junction hepatoid adenocarcinoma (GEJ HAC)using a case study and literature review.MethodsClinical presentation, results of histology and immunohistochemistry, and next-generation sequencing(NGS) in a patient with GEJ HAC metastasizing to the liver were reviewed. Chemotherapy (SOX or S-1) plus sintilimab was administered.ResultsA 65-year-old male patient with a history of hypertension was admitted to the hospital due to a one-week increase in serum AFP levels. There was a small intraluminal mass at the GEJ and a metastatic lesion in liver segment VIII, as well as enlarged perigastric and retroperitoneal lymph nodes. Tumor cells in both the GEJ and liver tissue exhibited a glandular shape with a nest-like adenoid structure. Immunohistochemical (IHC) analysis of the GEJ tissue showed positivity for AFP, CA19-9, CK7, CK20, MUC-1, P53 (wild type), Glypican-3, and HepPar-1, and negativity for Arginase-1, CD10, and Her-2. In the metastatic liver tissue, IHC testing demonstrated positivity for AFP, CD10, CK19, CK20, HepPar-1, MUC-1, Ki-67, and P53 (wild type), while CK7 was negative. The NGS report of GEJ mass indicated that the JAK2 and TP53 genes harbored missense mutations, while the MLH1, MSH2, MSH6, PMS2, ERBB2, EGFR, PIK3CA, APC, CTNNB1, CDH1, and DPYD genes were normal. The patient’s serum levels of CEA, CA19-9, and AFP were sharply decreased. The patient achieved a major pathological response (MPR) and remains in a progression-free stage.ConclusionsSintilimab-based chemotherapy has proven efficacy in achieving a MPR and maintaining a progression-free state for a patient with GEJ HAC that has metastasized to the liver.
Pilot clinical trial of neoadjuvant toll-like receptor 7 agonist (Imiquimod) immunotherapy in early-stage oral squamous cell carcinoma
Authors: Yoon Angela J. , Carvajal Richard D. , Graboyes Evan M. , Kaczmar John M. , Albergotti William G. , Kejner Alexandra E. , Troob Scott H. , Philipone Elizabeth , Anoma Jean-Sebastien , Armeson Kent E. , Hill Elizabeth G. , Richardson Mary S. , Woods Tina R. , Chera Bhishamjit S. , Nourollah-Zadeh Farzad , Lee Byung J. , Pandruvada Subramanya , Kourtidis Antonis , Kingsley Christina , O’Quinn Elizabeth C. , Mills Stephanie , Jordan Victoria C. , Spencer Mike , Fails Danielle , McKee Trevor D. , Zaidi Mark , Brisendine Alan , Horn Shane , Mehrotra Shikhar , Ogretmen Besim , Newman Jason G. 
Published: January 2025

BackgroundThere is no neoadjuvant immunotherapy for early-stage oral cancer patients. We report a single-arm, open-label, pilot clinical trial assessing the efficacy and safety of topical toll-like receptor-7 (TLR-7) agonist, imiquimod, utilized in a neoadjuvant setting in early-stage oral squamous cell carcinoma (OSCC).MethodsThe primary endpoint is reduction in tumor cell counts assessed by quantitative multiplex immunofluorescence and the immune-related pathologic response. The secondary endpoint is safety.Results60% of patients experienced a 50% reduction or greater in tumor cell count post-treatment (95% CI = 32% to 84%). Similarly, 60% of patients had immune-related major pathologic response (irMPR) with two complete pathologic responses, and 40% had partial response (PR) with the percent residual viable tumor ranging from 25% to 65%. An increase in functional helper and cytotoxic T-cells significantly contributed to a reduction in tumor (R=0.54 and 0.55, respectively). The treatment was well tolerated with the application site mucositis being the most common adverse event (grades 1-3), and no grade 4 life-threatening event. The median follow-up time was 17 months (95% CI = 16 months - not reached), and one-year recurrence-free survival was 93% of evaluable patients.ConclusionNeoadjuvant imiquimod immunotherapy could be safe and promising regimen for early-stage oral cancer.Trial registrationClinicalTrials.gov, Identifier NCT04883645.
Enhancing individuals’ engagement in marine recreational sport activities: from an institutional perspective
Authors: Shou Minghuan , Xu Jiawei 
Published: January 2025

IntroductionEncouraging consumer participation in marine recreational sport activities is recognized as a key strategy for boosting both local and regional economies. However, compared to other traditional outdoor activities, participation rates in marine recreation remain relatively low. Two major barriers to participation are consumers' concerns about whether marine recreational sport activities are interesting and suitable for themselves, which can be summarized into product quality uncertainty and product fit uncertainty.MethodsTo address this issue, this paper, grounded in institutional theory, investigates how different institutional environments influence consumers' product certainty and their behavioral engagement in marine recreational sport activities—an area previously underexplored in the literature.Results and discussionsBy collecting 292 survey responses and utilizing ordinary least squares (OLS) regression analysis, we found that both product quality certainty and product fit certainty have a significant positive effect on consumers' behavioral engagement. Additionally, both the regulatory-normative and cognitive institutional environments were shown to significantly enhance consumers' product quality and fit certainty. Moreover, age was found to moderate these effects, with a positive influence on the relationship between the regulatory-normative environment and product certainty, while only affecting the relationship between the cognitive institutional environment and product fit certainty.
Untargeted urine metabolomics reveals dynamic metabolic differences and key biomarkers across different stages of Alzheimer’s disease
Authors: Feng Xiaoya , Zhao Shenglan 
Published: January 2025

BackgroundAlzheimer’s disease (AD) is a progressive neurodegenerative disorder, with mild cognitive impairment (MCI) often serving as its precursor stage. Early intervention at the MCI stage can significantly delay AD onset.MethodsThis study employed untargeted urine metabolomics, with data obtained from the MetaboLights database (MTBLS8662), combined with orthogonal partial least squares-discriminant analysis (OPLS-DA) to examine metabolic differences across different stages of AD progression. A decision tree approach was used to identify key metabolites within significantly enriched pathways. These key metabolites were then utilized to construct and validate an AD progression prediction model.ResultsThe OPLS-DA model effectively distinguished the metabolic characteristics at different stages. Pathway enrichment analysis revealed that Drug metabolism was significantly enriched across all stages, while Retinol metabolism was particularly prominent during the transition stages. Key metabolites such as Theophylline, Vanillylmandelic Acid (VMA), and Adenosine showed significant differencesdifferencesin the early stages of the disease, whereas 1,7-Dimethyluric Acid, Cystathionine, and Indole exhibited strong predictive value during the MCI to AD transition. These metabolites play a crucial role in monitoring AD progression. Predictive models based on these metabolites demonstrated excellent classification and prediction capabilities.ConclusionThis study systematically analyzed the dynamic metabolic differences during the progression of AD and identified key metabolites and pathways as potential biomarkers for early prediction and intervention. Utilizing urinary metabolomics, the findings provide a theoretical basis for monitoring AD progression and contribute to improving prevention and intervention strategies, thereby potentially delaying disease progression.
Influence of strength and power training on the rate of force development, peak force and functional mobility in elderly people with Parkinson's disease: a randomized controlled trial
Authors: Amaral Felipe Késia Maísa do , Yamada Patrícia de Aguiar , Meneghetti Tamires , Faganello-Navega Flávia Roberta 
Published: January 2025

ObjectiveTo analyze the influence of lower limb muscle strength and muscle power training on rate of force development (RFD) and peak force (PF) in elderly people with Parkinson's disease (PD), as well as the effect of these training sessions influence on the functional mobility (FM) of this population.MethodsThis was a randomized controlled clinical trial and registered on the virtual platform for registration of experimental and non-experimental studies “Registro Brasileiro de Ensaios Clínicos (ReBEC)”. Thirty four elderly people of both genders without and with PD were divided into four groups: strength training control (GSC, n = 8); potency training control (GPC), n = 9; subjects with PD submitted to strength training (GSPD, n = 8); subjects with PD submitted to potency training (GPPD, n = 9). GSC and GPC consisted of with no history of neurological diseases. PF and RFD in the first 50 and 200 milliseconds (ms) were determined. FM was also assessed using the following tests: gait speed test (GS), Timed Up and Go (TUG), Short Physical Performance Battery (SPPB), Unified Parkinson's Disease Rating Scale (UPDRS); parallel feet on a force platform. Next, the participants underwent lower limbs muscle strength or muscle power training for eight consecutive weeks twice a week and were then re-evaluated.ResultsThe repeated measures ANOVA test showed a significant difference for PF, RFD and FM regardless of training type.ConclusionThe proposed muscle strength and muscle power training protocols influenced the increase in RFD, PF and FM of all participants; however, the increase in RFD in the first 200 ms was more pronounced in the groups submitted to power training and the increase in PF was more pronounced in the groups submitted to strength training.
RT-ring: a small wearable device for tremulous Parkinson’s disease diagnosis in primary care
Authors: Buonocore Jolanda , Vescio Basilio , De Maria Marida , Crasà Marianna , Nisticò Rita , Arcuri Pier P. , Cascini Giuseppe L. , Latorre Anna , Quattrone Aldo , Quattrone Andrea 
Published: January 2025

IntroductionDifferential diagnosis of rest tremor (RT) disorders is challenging, often requiring 123I-ioflupane single-photon-emission-computed tomography (DaTscan), an expensive technique not available worldwide. In the current study, we investigated the performance of a new wearable mobile device termed “RT-ring” in predicting DaTscan result in patients presenting with RT based on rest tremor inertial features.MethodsConsecutive RT patients underwent RT-ring tremor analysis, surface electromyography (sEMG), and DaTscan. The RT-ring is a miniaturized mobile device that uses machine learning based on inertial tremor data to estimate the RT pattern. This electrophysiologic tremor feature has proven to accurately predict DaTscan result. The primary outcome was the RT-ring’s performance in distinguishing patients with and without striatal dopaminergic deficit.ResultsSixty-seven RT patients were enrolled, including 42 patients with striatal dopaminergic deficit and 25 with normal DaTscan. The RT-ring showed 85.0% sensitivity, 90.9% specificity, and 87.9% balanced accuracy in predicting DaTscan result, and demonstrated 96.8% agreement with sEMG in RT pattern classification.ConclusionThe RT-ring is a promising, non-invasive, user-friendly, wearable mobile device for supporting the diagnosis of tremulous Parkinson’s disease in primary care settings, especially in low-income countries with limited access to dopamine imaging.
Female urethral diverticular carcinoma: a case report and review of the literature
Authors: Li Dan , Meng Fan Hua , Yang Xu 
Published: January 2025

ObjectiveTo investigate the etiology, clinical manifestations, treatment methods, and prognosis of urethral diverticulum cancer to enhance understanding of this disease.MethodsThis paper reports a case of urethral diverticulum cancer with “hematuria and dysuria” as the main clinical manifestations. The case is discussed in conjunction with relevant literature.ResultsThe patient initially presented to the gynecology department due to postmenopausal bleeding but was not diagnosed with the disease. Subsequently, the patient developed hematuria and dysuria and was referred to the urology department. MRI indicated urethral diverticulum-like changes with suspected tumorous lesions. Cystourethroscopic biopsy confirmed urethral diverticulum cancer. The patient underwent urethrectomy, and postoperative pathological diagnosis was poorly differentiated urothelial adenocarcinoma.ConclusionUrethral diverticulum cancer is a rare and highly aggressive malignant tumor of the urethra with a poor prognosis. The onset of urethral diverticulum cancer is concealed, and its clinical manifestations are nonspecific and diverse. Preoperative diagnosis is challenging, and imaging studies and cystourethroscopy are the primary preoperative diagnostic methods for urethral diverticulum cancer. Pathology and immunohistochemistry serve as the basis for confirmation of diagnosis. Currently, there is no unified treatment protocol for female urethral diverticulum cancer internationally. For female patients with urethral diverticulum cancer without distant metastasis, surgery remains the primary treatment. For patients with distant metastasis, a combination of surgery, chemotherapy, and radiotherapy may be considered.Genetic testing and targeted immunotherapy offer new approaches for future treatment.
Uridine-cytidine kinase 2 is correlated with immune, DNA damage repair and promotion of cancer stemness in pan-cancer
Authors: Tian Jinlong , Li Yanlei , Tong Yu , Zhang Yuan , Zhao Tingxiao , Kang Yao , Bi Qing 
Published: January 2025

BackgroundUCK2 (Uridine-Cytidine Kinase 2) is a promising prognostic marker for malignant tumors, but its association with immune infiltration and cancer stemness in pan-cancer remains to be fully understood. we find that gene UCK2 is closed related to RNA stemness scores (RNAss) and DNA stemness scores (DNAss), which is measured the tumor stemness. We also discover an association between UCK2 expression and immune cells by CIBERSORT algorithm, ESTIMATE algorithm and ssGSEA algorithm, especially, related to T cell, monocytes, mast cells, and macrophages. This study aims to shed light on the role and possible mechanism of UCK2 in pan-cancer.MethodsWe used the R programming language for pan-cancer bulk sequencing data analysis, which were obtained from the University of California, Santa Cruz (UCSC) datasets. UCSC database is a very useful for explore data from TCGA and other cancer genomics datasets, The data we explored at the UCK2 transcriptome level came from TCGA data in the UCSC database. We explored differential UCK2 expression between tumor and normal samples. Immunohistochemistry (IHC) was utilized to validate the expression of UCK2 in different types cancers using tumor tissue chips. The correlations of UCK2 with prognosis, genetic instability, DNA repair, cancer stem cell characteristics, and immune cell infiltration were investigated. Furthermore, single-cell datasets, acquired from the Gene Expression Omnibus (GEO) database, were used to validate the relationship between UCK2 and immune cells. GEO is a famous public genomics database supporting freely disseminates microarray data. Finally, we analyzed the correlation between UCK2 and drug sensitivity.ResultsUCK2 expression was observed to be high in most cancers and was remarkably related to the prognosis of pan-cancers. We found that the increased UCK2 expression was associated with higher genetic instability. Additionally, positive relationships were observed between UCK2 expression and mismatch repair genes, homologous recombination repair genes, and cancer stemness across different cancer types. There were significant correlations between UCK2 and T cells, monocytes, mast cells, and macrophages. Moreover, as expected, the immune checkpoint human leucocyte antigen (HLA) was found to be negatively related to UCK2. Similarly, UCK2 was also observed to have a negative association with major histocompatibility complex (MHC) genes. We noted that UCK2 had significant correlations with the sensitivity to various anti-cancer drug.ConclusionWe have observed that UCK2 plays pivotal roles in prognosis and tumor immunity, and it is associated with DNA repair and cancer stemness. The UCK2 gene exhibits a strong correlation with the immune checkpoints HLA. This study highlights its potential impact on drug sensitivity.
A telomere-related signature for predicting prognosis and assessing immune microenvironment in osteosarcoma
Authors: Li Shihao , Zhang Lina , Zhang Haiyang 
Published: January 2025

ObjectiveOsteosarcoma is the most common primary bone cancer with a high propensity for local invasion and metastasis. An increasing number of research studies show that telomeres play an important role in the occurrence and development of cancer. Thus, we established a telomere-related signature in osteosarcoma to comprehensively evaluate the pathogenic roles of telomeres in this disease.MethodsThe data on osteosarcoma were collected from the TARGET and Gene Expression Omnibus databases. First, we constructed a telomere-related signature using univariate and LASSO Cox regression analyses. Subsequently, we analyzed the prognostic value, functional annotation, immune microenvironment, and cell communication patterns of the telomere-related signature in osteosarcoma via comprehensive bioinformatics analyses. Cell proliferation was analyzed using the CCK-8 assay, and cell migration and invasion capabilities were evaluated using the Transwell assay.ResultsBased on the SP110, HHAT, TUBB, MORC4, TERT, PPARG, MAP3K5, PAGE5, MAP7, and CAMK1G, a telomere-related signature was built in osteosarcoma patients. The telomere-related signature could effectively predict the prognosis of osteosarcoma patients. The osteosarcoma patients in the high TELscore group exhibited poor prognosis. In addition, the telomere-related signature demonstrated predictive value for the immune microenvironment and drug sensitivity in osteosarcoma. Finally, we discovered significant reduction in MAP7 expression in osteosarcoma cells, and patients with low MAP7 expression had poor prognosis. Moreover, the overexpression of MAP7 significantly reduced cell proliferation, the ability of cell migration, and invasion in osteosarcoma cells.ConclusionA telomere-related signature was constructed in osteosarcoma patients, offering predictive values into prognosis, the immune microenvironment, and drug sensitivity. Moreover, MAP7 might serve as a prognostic marker for osteosarcoma patients.
Case report: Dysphonia associated with high-dose cytarabine therapy
Authors: Ma Ling , Huang Niya , Zhang Haixi , Liu Jia , Zhang Zhiqing 
Published: January 2025

Cytarabine is widely used in the treatment of hematological malignancies. Its common toxicities include myelosuppression and gastrointestinal disturbances. Additionally, it can cause central nervous system (CNS) symptoms, which include hoarseness, ataxic tremor, ataxic gait, nystagmus, dysmetria, and dysdiadochokinesia. In this article, we present the first case report of dysphonia, absent of CNS symptoms, induced by high-dose cytarabine (HiDAC) in a patient with acute myeloid leukemia. The patient’s voice began to change 3 days following the first cycle of HiDAC chemotherapy, and dysphonia recurred upon the reintroduction of HiDAC. To rule out other potential causes, a thorough examination and detailed medical history review were conducted, excluding factors such as vocal abuse, infection, effects of other medications, and underlying diseases as contributors to the dysphonia. The patient was diagnosed with HiDAC-induced dysphonia. This toxic effect was self-limiting, and the patient recovered in 10–15 days. Chemotherapy-induced dysphonia is a rarely reported and easily overlooked side effect. This adverse reaction is typically temporary and non-life-threatening; however, it substantially diminishes quality of life and may occasionally necessitate the discontinuation or postponement of chemotherapy. Physicians should be aware of this complication when administering chemotherapeutic agents.
Comprehensive chemical and bioactive investigation of Chinese peony flower: a case of valorization of by-products as a new food ingredient from Chinese herb
Authors: Peng Meng-ling , Gong Ming-Jiong , Zhang Jing , Gadetskaya Anastassiya V. , Liang Qian-Wen , He Pei-Wen , Qiu Xiao-Hui , Huang Zhi-Hai , Xu Wen 
Published: January 2025

IntroductionIn the present study, the flower of Chinese peony (CPF), major waste by-product of Chinese Herb Radix paeoniae, was comprehensively investigated for the first time.MethodsA validated UHPLC Orbitrap Mass spectrometry combined a three-levels characterization strategy were used to analyze CPF samples from four representative cultivars. The anti-inflammatory and antioxidant activities were analyzed using RAW264.7 cells, and DPPH, ABTS, FRAP, and ORAC antioxidant assays.ResultsA total of 150 chemical components were identified in CPF, among them, more than 50 components were reported from this species for the first time, with potential new chemicals reported. 67 quantified or semi-quantified targeted metabolomics analysis indicated a clear distinction between flower parts and four cultivars. CPF demonstrated significant antioxidant activities and displayed anti-inflammatory effects by reducing nitric oxide, IL-6, and TNF-a release in LPS-induced macrophages. Correlation analysis highlighted a strong positive correlation between total phenolic content and DPPH ABTS, and FRAP antioxidant activities.DiscussionThe present study is the first to comprehensively investigate the chemical profile and bioactivities of CPF, which provide insights into further understanding of its health-promoting potential.