bluuebunny/crossref_metadata_2025_split huggingface dataset:
Integrated multiomics analysis and machine learning refine neutrophil extracellular trap-related molecular subtypes and prognostic models for acute myeloid leukemia
Authors: Zhong Fangmin , Yao Fangyi , Wang Zihao , Liu Jing , Huang Bo , Wang Xiaozhong 
Published: February 2025

BackgroundNeutrophil extracellular traps (NETs) play pivotal roles in various pathological processes. The formation of NETs is impaired in acute myeloid leukemia (AML), which can result in immunodeficiency and increased susceptibility to infection.MethodsThe gene set variation analysis (GSVA) algorithm was employed for the calculation of NET score, while the consensus clustering algorithm was utilized to identify molecular subtypes. Weighted gene coexpression network analysis (WGCNA) revealed potential genes and biological pathways associated with NETs, and a total of 10 machine learning algorithms were applied to construct the optimal prognostic model.ResultsThrough the analysis of multiomics data, we identified two molecular subtypes with high and low NET scores. The low-NET score subgroup exhibited increased infiltration of immune effector cells. Conversely, the high-NET score subtype presented an abundance of monocytes and M2 macrophages, accompanied by elevated expression levels of immune checkpoint genes. These findings suggest that a pronounced immunosuppressive effect is associated with a significantly worse prognosis for this subtype. The optimal risk score model was selected by employing the C-index as the criterion on the basis of training 10 machine learning algorithms on 9 multicenter AML cohorts. Survival analysis confirmed that patients with high-risk scores had considerably poorer prognoses than those with lower scores. Receiver operating characteristic (ROC) curve and Cox regression analyses further validated the strong independent prognostic value of the risk score model. The nomogram, which was constructed by integrating the risk score model and clinicopathological factors, demonstrated high accuracy in predicting the overall survival of AML patients. Moreover, patients with refractory or chemotherapy-unresponsive AML had significantly higher risk scores. By analyzing drug therapy data from in vitro AML cells, we identified a subset of drugs that demonstrated increased sensitivity in the high-risk score group. Additionally, patients with a high risk score were also predicted to exhibit a favorable response to anti-PD-1 therapy, suggesting that these individuals may derive greater benefits from immunotherapy.ConclusionThe NET-related signature, derived from a combination of diverse machine learning algorithms, has promising potential as a valuable tool for prognostic prediction, preventive measures, and personalized medicine in patients with AML.
Somatic mutations in Brazilian patients with paroxysmal nocturnal hemoglobinuria: a comprehensive analysis
Authors: Eiko Yamakawa Patricia , Perez Gomes Caio , Ribeiro Mendes Agatha , Cesar Justino de Oliveira Caio , Porto Freitas Florencio , Bettoni Fabiana , Xavier dos Santos Ernande , Campos de Molla Vinicius , Vescovi Gonçalves Matheus , Branquinho Jessica , Ribeiro Nogueira Beatriz , Bosco Pesquero Joao , Arrais-Rodrigues Celso 
Published: February 2025

BackgroundParoxysmal nocturnal hemoglobinuria (PNH) is a rare clonal hematopoietic stem cell disease characterized by acquired abnormalities in the phosphatidylinositol glycan class A (PIG-A) gene.MethodsThis study analyzed PIG-A gene using polymerase chain reaction (PCR) followed by Sanger sequencing of 31 Brazilian patients with PNH, including 23 with classical PNH and 8 with subclinical PNH (aplastic anemia and a PNH clone).ResultsA diverse spectrum of acquired PIG-A variants was identified, encompassing insertions, deletions, and single-base substitutions. The majority of variants identified (17 out of 29) were deemed likely pathogenic for paroxysmal nocturnal hemoglobinuria (PNH). Six variants have undetermined significance (VUS) and six variants are probably benign. Somatic variants exhibited variability in type and location among the patients, with a predominance of small deletions and simple base changes. Notably, 41% of the variants were frameshift and 35% were missense. Among the 23 patients with hemolytic PNH, 19 had at least one detectable pathogenic variant. Subclinical PNH cases were characterized solely by polymorphisms.ConclusionIn conclusion, the somatic variants in Brazilian PNH patients displayed variability in both site distribution and type. Contrary to mutational hotspots observed in previous studies, none were identified in this cohort. No specific correlation between the clinical characteristics of hemolytic PNH patients and their variants was found, likely due to the extensive variety of mutations.
Development and validation of a dynamic nomogram for acute kidney injury prediction in ICU patients with acute heart failure
Authors: Feng Lu-Huai , Su Tingting , Huang Lina , Liao Tianbao , Lu Yang , Wu Lili 
Published: February 2025

ObjectiveDeveloping and validating a simple and clinically useful dynamic nomogram for predicting early acute kidney injury (AKI) in patients with acute heart failure (AHF) admitted to the intensive care unit (ICU).MethodsClinical data from patients with AHF were obtained from the Medical Information Mart for Intensive Care IV database. The patients with AHF were randomly allocated into derivation and validation sets. The independent predictors for AKI development in AHF patients were identified through least absolute shrinkage and selection operator and multivariate logistic regression analyses. A nomogram was developed based on the results of the multivariable logistic regression to predict early AKI onset in AHF patients, which was subsequently implemented as a web-based calculator for clinical application. An evaluation of the nomogram was conducted using discrimination, calibration curves, and decision curve analyses (DCA).ResultsAfter strict screening, 1,338 patients with AHF were included in the derivation set, and 3,129 in the validation set. Sepsis, use of human albumin, age, mechanical ventilation, aminoglycoside administration, and serum creatinine levels were identified as predictive factors for AKI in patients with AHF. The discrimination of the nomogram in both the derivation and validation sets was 0.81 (95% confidence interval: 0.78–0.83) and 0.79 (95% confidence interval: 0.76–0.83). Additionally, the calibration curve demonstrated that the predicted outcomes aligned well with the actual observations. Ultimately, the DCA curves indicated that the nomogram exhibited favorable clinical applicability.ConclusionThe nomogram that integrates clinical risk factors and enables the personalized prediction of AKI in patients with AHF upon admission to the ICU, which has the potential to assist in identifying AHF patients who would derive the greatest benefit from interventions aimed at preventing and treating AKI.
The influence of circadian rhythm disruption during Ramadan on metabolic responses to physical activity: a pilot study
Authors: Anwardeen Najeha Rizwana , Naja Khaled , Almuraikhy Shamma , Sellami Maha , Al-Amri Hadaia Saleh , Philip Nebu , Tamimi Faleh , Agil Ahmed , Elrayess Mohamed A. 
Published: February 2025

BackgroundCircadian rhythms and sleep patterns are important regulators of metabolic health. During Ramadan intermittent fasting (RIF), the sleep–wake cycles are often disrupted, which can affect physical activity (PA) and related metabolic responses. Limited knowledge is available on how sleep disruption influences PA in the general population during RIF. This pilot study aimed to examine the metabolic responses to moderate PA under normal and disrupted sleep patterns during RIF.MethodsA pilot study was conducted on 12 participants comprising of individuals with normal (n = 5) and disrupted sleep patterns (n = 7). Blood samples were collected, and measurements of clinical traits, cytokines, homeostasis model assessment of insulin resistance (HOMA-IR) and metabolic profiles were performed before and after intervention. Orthogonal partial least square – discriminant analysis (OPLS-DA) and linear regressions were performed to assess metabolic responses to PA during RIF under different patterns.Results and conclusionFasting participants with normal sleep patterns exhibited lower HOMA-IR (β = −0.416, p = 0.047) in response to PA compared to those with disrupted sleep. Additionally, they demonstrated more efficient lipid utilization during PA, characterized by reduced diacylglycerol levels, which could enhance insulin sensitivity and lower the risk of type 2 diabetes. In contrast, fasting participants with disrupted sleep patterns experienced metabolic stress, marked by significant depletion of polyunsaturated fatty acids (PUFAs), monounsaturated fatty acids (MUFAs), and plasmalogens in response to PA. These changes were associated with increased inflammation and oxidative stress, potentially leading to metabolic dysregulation.
Efficacy and safety of nanoparticle albumin-bound paclitaxel plus cisplatin or nedaplatin plus tegafur/gimeracil/oteracil as induction chemotherapy regimen for hypopharyngeal cancer
Authors: Jiang Cailing , Liu Yulan , Mo Yunyan , Xu Lieyin , Zhu Lin , Li Zhenya , Xu Shengyuan , Qin Xi , Wu Guangteng , Kang Mafei , He Xiaosong , Xue Feng 
Published: February 2025

BackgroundTreatment of hypopharyngeal carcinoma involves surgery, radiotherapy, and chemotherapy. The combination of docetaxel, cisplatin, and 5-fluorouracil as a standard induction chemotherapy regimen allows enhanced laryngeal preservation after surgery. In this study, our objective was to retrospectively analyze the short-term efficacy and adverse events of nab-paclitaxel plus cisplatin or nedaplatin plus tegafur/gimeracil/oteracil as an induction chemotherapy regimen for hypopharyngeal cancer.MethodsThis retrospective study involved 19 patients who received nab-paclitaxel plus cisplatin/nedaplatin plus tegafur/gimeracil/oteracil every 21 days intervals for three cycles at the Affiliated Hospital of Guilin Medical University (December 2020 to February 2023). The primary endpoint was progression-free survival. Adverse events were assessed in all patients.ResultsTreatment response was evaluated after the second cycle. Clinical outcomes indicated that 2 (10.53%), 15 (78.94%), and 2 (10.53%) patients exhibited clinical complete response, partial response, and stable disease, respectively. The objective response and disease control rates were 89.47% (17/19) and 100%, respectively. The pathological complete response rate was 71.43% (5/7) among the seven patients who underwent surgery after three cycles. Following induction chemotherapy, 4 (21.05%), 2 (10.53%), and 2 (10.53%) patients received radiotherapy, chemotherapy, and chemotherapy plus immunotherapy, respectively, whereas 4 (21.05%) patients discontinued treatment. At the 17.43-month median follow-up, median progression-free survival was 17.6 months (95% confidence interval, 13.9-21.2). The most common grade 3 treatment-related adverse events were alopecia (36.8%), leukopenia (26.3%), and anemia (15.8%). No grade 4/5 treatment-emergent adverse events were observed.ConclusionsThe combination of nab-paclitaxel, cisplatin/nedaplatin, and tegafur/gimeracil/oteracil is a safe induction chemotherapy for treating hypopharyngeal cancer.
Cepharanthine hydrochloride: a novel ferroptosis-inducing agent for prostate cancer treatment
Authors: Guan Jing-Song , Jia Jing , Huang Ze-Xiu , Zhou Yu-Qing , Zheng Jing-Jie , Lin Qi-Man , Wang Yi-Fei , Fan Jiang-Lin , Wang Yao 
Published: February 2025

BackgroundFerroptosis is an intracellular iron-dependent cell death that is distinct from apoptosis, necrosis, and autophagy. Increasing evidence indicated that ferroptosis plays a crucial role in suppressing tumors, thus providing new opportunities for cancer therapy. The drug cepharanthine, commonly used to treat leukopenia, has been discovered to function as an anticancer agent to multiple types of cancer via diverse mechanisms. However, the effect of cepharanthine on prostate cancer remains unclear.MethodsA semi-synthetic derivative of cepharanthine, cepharanthine hydrochloride (CH), is used in this study due to its better water solubility and bioavailability. The prostate cancer cell lines LNCaP, 22Rv1, PC3 and xenograft mouse models are used for detecting the anti-tumor effect of CH in vitro and in vivo. Types of cell death including ferroptosis are detected by flow cytometry using annexin V and total/lipid reactive oxygen species probes, drug combination of CH with ferroptosis inhibitor/ion chelator, and the appearance of mitochondria under a transmission electron microscopy. The mechanism is investigated by high-throughput transcriptome analysis and transcription factor function analysis of androgen receptor.ResultsCH inhibits cellular functions and trigger ferroptosis in prostate cancer cells. Mechanistic research revealed both common and distinct pharmacological mechanisms of CH-induced ferroptosis in different prostate cancer cells. High-throughput transcriptome analysis revealed that ferroptosis-related genes are significantly regulated in androgen receptor-dependent cells 22Rv1 and LNCaP, and less significantly in androgen receptor-independent cell PC3. Furthermore, CH was found to reduce the gene expressions and protein levels of GPX4 and FSP1 through modulating the activity of the androgen receptor signaling pathway, but not through its transcription factor activity. In addition, CH upregulated ACSL4 and downregulated DHODH, with the combined regulatory outcomes synergistically inducing ferroptosis. An in vivo experiment employing CH and ion chelator-treated nude mice validated the mechanism by which CH induces ferroptosis to combat prostate cancer.ConclusionThis study has identified CH as a novel ferroptosis-inducing agent for the treatment of prostate cancer. The multiple mechanisms we found provides strong evidence for the eventual clinical application of the drug.
Intestinal current measurement detects age-dependent differences in CFTR function in rectal epithelium
Authors: Graeber Simon Y. , Sommerburg Olaf , Yu Yin , Berges Julian , Hirtz Stephanie , Scheuermann Heike , Berger Jasmin , Duerr Julia , Mall Marcus A. 
Published: February 2025

ObjectiveIntestinal current measurement (ICM) provides a sensitive bioassay for assessment of cystic fibrosis transmembrane conductance regulator (CFTR) function in rectal biopsies ex vivo and is used as a diagnostic tool for cystic fibrosis (CF). Furthermore, ICM was shown to be sensitive to detect pharmacological rescue of CFTR function by CFTR modulators in people with CF carrying responsive CFTR mutations. Results from clinical trials of CFTR modulators across age groups indicate that CFTR function in the sweat duct may be age-dependent with children reaching higher levels than adults. However, little is known about age dependency of CFTR function in the intestinal epithelium.MethodsWe investigated CFTR-mediated chloride secretion in rectal biopsies from 258 people without CF and 72 people with pancreatic-insufficient CF from 1 month to 68 years of age. Change in transepithelial short-circuit current in response to cyclic adenosine monophosphate (cAMP)-mediated (100 μM IBMX, 1 µM forskolin, basolateral) and cholinergic (100 μM carbachol, basolateral) stimulation was assessed as a readout for CFTR function using perfused micro-Ussing chambers. Furthermore, quantitative real-time PCR of CFTR and morphometric analysis of epithelial cells lining the crypts and surface of the rectal mucosa were performed to assess regulation at the levels of gene expression and epithelial cell densities.ResultsWe found that CFTR-mediated chloride secretion across rectal tissues, as determined from cAMP-mediated as well as cholinergic chloride-secretory responses was highest during infancy and early childhood and declined with age in people without CF (both P &lt; 0.001). Although, there was no difference in cAMP-mediated currents in people with CF, potassium-secretory responses induced by cholinergic stimulation were also reduced with increasing age. Transcript analyses showed that CFTR mRNA expression was slightly increased with increasing age in people without CF (P &lt; 0.05). Morphometric analyses demonstrated that CFTR expressing colonocytes at the crypt base were decreased with age (P &lt; 0.05). A secondary analysis of the ICM data of our previous studies on the effects of lumacaftor/ivacaftor on CFTR function in F508del -homozygous people with CF aged 12 years and older and 2–11 year old children showed correlations of the change in cAMP-mediated and cholinergic chloride secretory response with the age of people with CF (P &lt; 0.01 and P &lt; 0.05, respectively).ConclusionThese results demonstrate that CFTR function in the rectal epithelium is reduced with increasing age and indicate that this change is likely due to a decline in the number of secretory colonocytes at the crypt base. These findings suggest that differences in CFTR expressing cells may explain increased functional responses to CFTR modulator therapies in children compared to adult people with CF.
Gold complex QB1561 suppresses drug-resistant cancer cells by inhibiting TrxR and mitochondrial respiratory function
Authors: Gao Hai-Ling , Ding Wenwen , Shen Zhi-Xin , Cui Qingbin 
Published: February 2025

IntroductionMulti-drug resistance (MDR) is one of the leading reasons that cause the failures of cancer treatment. Novel agents that may reverse MDR and neutralize drug-resistant cancer cells are highly desirable for clinical practice. The targeting of cellular redox homeostasis and/or mitochondria-mediated energy metabolism are promising strategies for the suppression of drug-resistant cancer cells. Based on the structure of mono-gold(I) complex auranofin (AF), a drug candidate under clinical trials for cancer, we synthesized a new dual-gold(I) complex QB1561 and tested if it can inhibit drug-resistant cancer cells overexpressing ATP-binding cassette (ABC) transporters. We also investigated if QB1561 could inhibit thioredoxin reductase (TrxR), a well-known target of AF and other gold complexes, and assessed its impact on mitochondrial respiration.MethodologyCell viability of drug-resistant cells upon QB1561 alone or combined with topotecan and mitoxantrone was determined by MTS assay. The expression of ABC sub-family G member 2 (ABCG2) in the lung cancer cell line NCI-H460/MX20 after treatment with QB1561 was assessed by Western blot. The Vi-sensitive ABCG2 ATPase activity in the membrane vesicles of High Five insect cells, TrxR activity, and ROS production were measured following QB1561 treatment. Colony formation was used to assess QB1561’s anticancer potential. SeaHorce Seahorse XF Analyzers were used to measure the oxygen consumption rate (OCR).ResultsQB1561 suppressed the proliferation of drug-resistant cancer cells overexpressing ABC transporters, with IC50 values ranging from 0.57 to 1.80 μM, which was more effective than AF. QB1561 was able to partially reverse the resistance of mitoxantrone and topotecan in lung cancer NCI-H460/MX20 cells which overexpressed ABCG2, without altering the expression levels of ABCG2. QB1561 suppressed the colony formation of NCI-H460/MX20 cells, probably via ROS induction due to TrxR inhibition. QB1561 also efficiently suppressed OCR, suggesting its inhibition on mitochondrial respiration.ConclusionQB1561 was effective for the treatment of MDR in drug-resistant cancer cells. Its further evaluation could be useful for the design and development of more gold-based anticancer drugs.
Validation of the Contextual Sensation-Seeking Questionnaire for skiing and snowboarding among Chinese adult skiers and its relationship with risk-taking behavior
Authors: Guo Zeyou , Gao Shenmao , Liu Yuanguo , Zhang Renfang , Dou Guangbo 
Published: February 2025

ObjectiveTo validate the reliability and validity of the Contextual Sensation-seeking Questionnaire for Skiing and Snowboarding (CSSQ-S) among Chinese adult skiers, and to explore the relationship between sensation seeking and risk-taking behavior.MethodsSnowball sampling was employed to gather data from 515 individuals, aged between 18 and 40 years old, with at least one year of experience in skiing or snowboarding. Exploratory factor analysis (EFA), confirmatory factor analysis (CFA), and other statistical methods were utilized for data analysis.ResultsThe CSSQ-S demonstrated strong factor validity, internal consistency, and construct validity. Sensation seeking was significantly positively correlated with injury frequency, and risk perception mediated this relationship.ConclusionThe CSSQ-S can be regarded as a reliable and valid tool for measuring sensation-seeking levels and potential injury risks among Chinese adult skiers, providing a useful reference for ski safety management and training.
Prevalence trend and burden of foodborne trematodiasis in China from 1990 to 2021 and its predictions until 2030: a comparative study with Japan and South Korea
Authors: Ma Runzhou , Li Na , Chen Chengming , Lan Jianqiang , Guo Huaibin , Zhang Wanxing 
Published: February 2025

BackgroundFoodborne trematodiasis (FBT) poses a significant public health challenge in East Asia, influenced by local dietary practices and environmental conditions. This study evaluates the prevalence trends and disease burden of FBT in China, Japan, and South Korea from 1990 to 2021, with future burden projections until 2030, to guide targeted prevention strategies and public health resource allocation.MethodsThe study utilized data from the Global Burden of Disease (GBD) 2021, including the absolute prevalence, age-standardized prevalence rate (ASPR), disability-adjusted life years (DALYs), and age-standardized DALY rate (ASDALR). Joinpoint regression analyzed the average annual percentage change (AAPC) and 95% confidence intervals (CI) to track FBT burden trends. A comparative analysis was conducted across different dimensions of the burden of FBT among China, Japan, and South Korea, including age, gender, and temporal trends. Additionally, the Bayesian age-period-cohort (BAPC) model projected future FBT burden trends.ResultsFrom 1990 to 2021, China showed significant reductions in ASPR (41.65%) and ASDALR (47.44%) of FBT. South Korea also noted a slight decrease, yet both had higher rates than the global average. Japan, conversely, saw a notable increase in FBT burden but with an overall lower burden compared to the global average. Males generally exhibited a higher disease burden than females. Future projections indicate a continued decline or stabilization in China and Japan, with a potential slight increase in South Korea by 2030.ConclusionThe study reveals contrasting trends in FBT burden among the three East Asian countries, with significant declines in China, a slight decrease in South Korea despite higher-than-global rates, and an increasing but low burden in Japan. These insights are crucial for tailoring public health interventions and allocating resources effectively to combat FBT in the region.