bluuebunny/crossref_metadata_2025_split huggingface dataset:
Integration of scRNA-seq and bulk RNA-seq to reveal the association and potential molecular mechanisms of metabolic reprogramming regulated by lactylation and chemotherapy resistance in ovarian cancer
Authors: Ren Fang , Pang Xiaoao , Jin Feng , Luan Nannan , Guo Houhua , Zhu Liancheng 
Published: February 2025

ObjectiveOvarian cancer (OC) ranks among the foremost causes of mortality in gynecological malignancies, with chemoresistance being the primary factor contributing to unfavorable prognosis. This work seeks to clarify the mechanisms of resistance-related lactylation in OC, intending to offer novel theoretical foundations and therapy strategies for addressing chemoresistance.MethodsThrough the combined analysis of bulk RNA-seq and single-cell RNA-seq data, we initially found lactylation genes linked to chemoresistance. Subsequently, we employed differential expression analysis, survival analysis, enrichment analysis, and other methodologies to further investigate the roles and molecular mechanisms of these genes in tumor resistance. Ultimately, we investigated the differential expression of these genes in resistant and non-resistant tissues and cells via experimentation.ResultsWe found two candidate genes associated with lactylation chemoresistance, ALDH1A1 and S100A4. Analysis of single-cell data indicated that tumor cells represent the primary cell subpopulation relevant to resistance studies. Subpopulation analysis indicated that several tumor cell subtypes were markedly linked to resistance, with elevated expression levels of ALDH1A1 and S100A4 in the resistant subpopulation, notably correlating with various immunological and metabolic pathways. Analysis of metabolic pathways indicated that oxidative phosphorylation and glycolysis activity was elevated in the resistant subpopulation, and lactic acid buildup was associated with chemoresistance. The investigation of the marker gene protein-protein interaction network in the resistant subgroup elucidated the intricate interactions among these genes. The expression levels of ALDH1A1 and S100A4 in the OC tissues of the platinum-resistant cohort were markedly elevated compared to the sensitive cohort, with a considerable rise in S100A4 expression observed in resistant OC cells, demonstrating co-localization with lactylation.ConclusionThis work elucidates the significant function of lactylation in OC chemoresistance and identifies ALDH1A1 and S100A4 as possible genes associated with drug resistance. These findings enhance our comprehension of the mechanisms behind chemoresistance in OC and offer critical insights for the formulation of novel therapeutic options.
Metabolic pathway activation and immune microenvironment features in non-small cell lung cancer: insights from single-cell transcriptomics
Authors: Liu Yanru , Liu Hanmin , Xiong Ying 
Published: February 2025

IntroductionIn this study, we aim to provide a deep understanding of the tumor microenvironment (TME) and its metabolic characteristics in non-small cell lung cancer (NSCLC) through single-cell RNA sequencing (scRNAseq) data obtained from public databases. Given that lung cancer is a leading cause of cancer-related deaths globally and NSCLC accounts for the majority of lung cancer cases, understanding the relationship between TME and metabolic pathways in NSCLC is crucial for developing new treatment strategies.MethodsFinally, machine learning algorithms were employed to construct a risk signature with strong predictive power across multiple independent cohorts. After quality control, 29,053 cells were retained, and PCA along with UMAP techniques were used to distinguish 13 primary cell subpopulations. Four highly activated metabolic pathways were identified within malignant cell subpopulations, which were further divided into seven distinct subgroups showing significant differences in differentiation potential and metabolic activity. WGCNA was utilized to identify gene modules and hub genes closely associated with these four metabolic pathways.ResultsOur analysis showed that DEGs between tumor and normal tissues were predominantly enriched in immune response and cell adhesion pathways. The comprehensive examination of our model revealed substantial variations in clinical and pathological characteristics, enriched pathways, cancer hallmarks, and immune infiltration scores between high-risk and low-risk groups. Wet lab experiments validated the role of KRT6B in NSCLC, demonstrating that KRT6B expression is elevated and it stimulates the proliferation of cancer cells.DiscussionThese observations not only enhance our understanding of metabolic reprogramming and its biological functions in NSCLC but also provide new perspectives for early detection, prognostic evaluation, and targeted therapy. However, future research should further explore the specific mechanisms of these metabolic pathways and their application potentials in clinical practice.
Typing of Echinococcus multilocularis by Region-Specific Extraction and Next-Generation Sequencing of the mitogenome
Authors: Rachel Franziska , Luttermann Christine , Höper Dirk , Conraths Franz Josef , Dapprich Johannes , Maksimov Pavlo 
Published: February 2025

BackgroundInfection by the fox tapeworm Echinococcus multilocularis may lead to a severe zoonosis in humans, alveolar echinococcosis, which may be fatal if left untreated. Typing is important to understand the epidemiology of this parasite, yet there is limited knowledge on the microdiversity of E. multilocularis on the local scale, since the typing resolution of established methods is restricted.MethodsThe mitogenome of E. multilocularis was used as the target regions to modify, apply and validate the Region-Specific Extraction (RSE) method in combination with Next-Generation Sequencing (NGS). Single Nucleotide Polymorphisms (SNPs) were detected in the mitochondrial DNA (mtDNA) and analysed bioinformatically. To validate the success and the accuracy of the RSE protocol, the mitogenomes of some E. multilocularis isolates were also analysed by the Whole-Genome Sequencing (WGS).ResultsWith the chosen combination of methods, the entire mitogenome (~13 kb) of E. multilocularis could be captured and amplified. The read depth (median ≥ 156X) was sufficient to detect existing SNPs. The comparison of mitogenome sequences extracted by RSE with mitogenome sequences obtained by WGS showed that the accuracy of the RSE method was consistently comparable to direct Whole-Genome Sequencing.ConclusionThe results demonstrate that the RSE method in combination with NGS is suitable to analyse the microdiversity of E. multilocularis at the whole mitogenome level. For the capture and sequencing of large (several kb) genomic regions of E. multilocularis and other applications, this method can be very helpful.
Dietary protein requirements of older adults with sarcopenia determined by the indicator amino acid oxidation technology
Authors: Wu Wenxuan , Chen Fengge , Ma Hui , Lu Jiaxi , Zhang Yanhong , Zhou Haisong , Yang Yunqi , Nie Shuhui , Wang Rui , Yue Weixiao , Li Min , Yang Xiaoguang 
Published: February 2025

BackgroundAlthough protein supplementation may be desirable in the management of sarcopenia, the appropriate protein requirements for older adults with sarcopenia are presently unclear.ObjectiveThe aim of this study was to determine the protein requirements of older adults (65–81 year) with sarcopenia by using the indicator amino acid oxidation (IAAO) technology.MethodsNine older adults with sarcopenia (four male participants and five female participants) participated in the study, with protein intakes ranging from 0.1 to 1.8 g/(kg·d). Each participant consumed an adapted diet with a protein level of 1.0 g/(kg·d) and 1.7 resting energy expenditure (REE) for 2 day. Day 3 was the oxidation day of the study. Diets that delivered energy at a 1.5 × REE were isocaloric. The amounts of phenylalanine and tyrosine maintained at a constant across intakes. Therefore, phenylalanine and tyrosine were added to the protein doses of 0.1–1.5 g/kg, which was based on the highest dose of lactalbumin content [1.8 g/(kg·d)]. Applying a non-linear mixed-effects model analysis of F13CO2, the protein requirement was determined by identifying the breakpoint in the F13CO2 data with graded amounts of dietary protein.ResultsThe mean estimated average requirement (EAR) and recommended nutrient intake (RNI) of protein for older adults with sarcopenia were 1.21 (95% CI: 0.95, 1.46) and 1.54 (95% CI: 1.13, 1.95) g/(kg·d), respectively.ConclusionsTo our knowledge, this is the first study of protein intake in older adults with sarcopenia and indicates that older adults with sarcopenia may require a higher intake of dietary protein.Clinical trial registrationhttp://www.chictr.org.cn, ChiCTR2200061383.
Development and validation of a prognostic nomogram for early hepatocellular carcinoma treated with microwave ablation
Authors: Zhang Jing , Guo Guanya , Li Tao , Guo Changcun , Han Ying , Zhou Xinmin 
Published: February 2025

ObjectiveAn effective model for risk stratification and prognostic assessment of early hepatocellular carcinoma (HCC) patients following microwave ablation (MWA) is lacking in clinical practice. The aim of this study is to develop and validate a prognostic model specifically for these patients.MethodsBetween January 2008 and December 2018, 345 treatment-naïve patients with HCC conforming to the Milan criteria who underwent MWA were enrolled and randomly assigned to the training (n=209) and validation (n=136) cohorts. The nomogram model was constructed based on the predictors assessed by the multivariate Cox proportional hazards model and validated. Predictive accuracy and discriminative ability were further evaluated and compared with other prognostic models.ResultsAfter a median follow-up of 59.0 months, 52.5% (187/356) of the patients had died. Prognostic factors for overall survival (OS) were α-fetoprotein (AFP), albumin-bilirubin (ALBI) score, platelets, and ablation margins, which generated the nomograms. The nomogram model consistently achieved good calibration and discriminatory ability with a concordance index of 0.64 (95% confidence interval (CI): 0.59-0.69) and 0.69 (95% CI: 0.63-0.75) in both the training and validation cohorts. The performance of the nomogram model also outperformed other prognostic models. By using the nomogram model, the patient population could be correctly divided into low- and high-risk strata presenting significantly different median OS of 105.0 (95% CI: 84.1-125.9) months, and 45.0 (95% CI: 28.0-62.0) months, respectively.ConclusionThe nomogram model based on AFP, PLT, ablation margins, and ALBI score was a simple visualization model that could stratify patients with early‐stage HCC after MWA and predict individualized long-term survival with favorable performance.
Photodynamic therapy and tumor-treating fields therapy for newly diagnosed glioblastoma
Authors: Fukami Shinjiro , Nagai Kenta , Onodera Sho , Saito Yuki , Akimoto Jiro , Kohno Michihiro 
Published: February 2025

Introduction and purposeVarious treatment methods, including photodynamic therapy (PDT), are used for glioblastoma (GBM), which is an intractable tumor. Our therapeutic strategy for glioblastoma has been based on resection (if possible), and PDT. On the other hand, after tumor-treating fields therapy (TTF) became available, we have actively recommended it to our patients who are eligible for it. In this report, we describe the clinical characteristics and disease course of glioblastoma patients treated by PDT + TTF at our hospital.MethodsA total of 14 patients with newly diagnosed glioblastoma, who underwent PDT + TTF from the time of insurance coverage of TTF were analyzed. The median age of the patients was 48 years. There were 10 men and 4 women, with a high prevalence of younger men.ResultsThe average duration of TTF was 8.9 (1–19) months, and the main reasons for its discontinuation were recurrence of the tumor and scalp problems. The median progression-free survival of the 14 patients who underwent PDT + TTF was 13.4 months, which tended to be longer than that of the 30 patients who underwent PDT without TTF (11 months). Of the 10 patients who relapsed, 2 had local recurrence and 8 had distant or disseminated recurrence. Two patients with local recurrence underwent repeat resection together with PDT. To date, the prognosis for patient survival of PDT + TTF appears favorable, with 6 patients surviving for more than 2 years.ConclusionPDT + TTF treatment for newly diagnosed glioblastoma can be performed without any major adverse events, although there are some problems with the continuation of TTF, such as scalp problems and its high cost. More patients who underwent PDT + TTF relapsed with distant and/or disseminated recurrence than local recurrence, suggesting that this treatment strategy targets local recurrence. Our results demonstrate that combination therapy for newly diagnosed glioblastoma with PDT + TTF may prolong the time to recurrence and improve survival outcomes of patients, although the data in this study are preliminary.
Undergraduate pharmacy students’ preference for case-based learning: a discrete choice experiment in China
Authors: Guo Zhibo , He Yuxing , Yan Jianzhou 
Published: February 2025

BackgroundUnderstanding students’ preferences is crucial for developing targeted teaching strategies and improving educational outcomes. This study aimed to investigate Chinese undergraduate pharmacy students’ preferences for case-based learning (CBL).MethodsWe conducted a discrete choice experiment (DCE) to quantify preferences for CBL. Six key attributes associated with CBL preferences were identified: case modality, provider type, group size, case authenticity, case complexity, and examination format. An online questionnaire was administered to undergraduate pharmacy students from two universities in China. The data were analyzed using a mixed logit model to estimate preference weights, assess the relative importance of the attributes, and predict uptake rates. Additionally, interaction effects and subgroup analysis were employed to identify heterogeneity in preferences among different student groups.ResultsA total of 613 participants completed the questionnaire and 482 participants were included in the analysis. The most influential attribute was case modality, with scenario simulation strongly preferred over paper modality. Case authenticity and provider type were also significant factors, followed by group size and case complexity. Examination format did not significantly affect preferences. We found heterogeneity in preferences between different groups of students. The highest uptake was achieved when cases were presented in scenario simulations by clinical instructors in small groups, using real cases of low complexity alongside the traditional written examination.ConclusionThe study highlights the importance of case modality with scenario simulation, case authenticity, and provider by clinical instructors among Chinese undergraduate pharmacy students for CBL, and suggests the need for personalized CBL approaches to accommodate different preferences.
Administration of the KCa channel activator SKA-31 improves endothelial function in the aorta of atherosclerosis-prone mice
Authors: Vera O. Daniel , Mishra Ramesh C. , Khaddaj-Mallat Rayan , Hamm Liam , Almarzouq Barak , Chen Yong-Xiang , Belke Darrell D. , Singh Latika , Wulff Heike , Braun Andrew P. 
Published: February 2025

IntroductionAtherosclerosis remains a major risk factor for vascular dysfunction and cardiovascular (CV) disease. Pharmacological enhancement of endothelial Ca2+-activated K+ channel activity (i.e., KCa2.3 and KCa3.1) opposes vascular dysfunction associated with ageing and type 2 diabetes (T2D) in ex vivo and in vivo preparations. In the current study, we have investigated the efficacy of this strategy to mitigate endothelial dysfunction in the setting of atherogenesis.MethodsMale apolipoprotein E knockout (Apoe−/−) mice fed a high fat diet (HFD) were treated daily with the KCa channel activator SKA-31 (10 mg/kg), the KCa3.1 channel blocker senicapoc (40 mg/kg), or drug vehicle for 12-weeks. Endothelium-dependent and -independent relaxation and vasocontractility were measured in abdominal aorta by wire myography. The development of atherosclerosis in the thoracic aorta was characterized by Oil Red O staining and immunohistochemistry. Key vasorelaxant signaling proteins were quantified by q-PCR.ResultsEndothelium-dependent relaxation of phenylephrine-constricted aortic rings was impaired in Apoe−/− HFD mice (53%) vs. wild-type (WT) controls (80%, P &lt; 0.0001), consistent with endothelial dysfunction. Treatment of Apoe−/− HFD mice with SKA-31, but not senicapoc, restored maximal relaxation to the WT level. Phenylephrine-evoked contraction was similar in WT and vehicle/drug treated Apoe−/− mice, as was the maximal relaxation induced by the endothelium-independent vasodilator sodium nitroprusside. mRNA expression for eNOS, KCa3.1, KCa2.3 and TRPV4 channels in the abdominal aorta was unaffected by either SKA-31 or senicapoc treatment. Fatty plaque formation, tissue collagen, α-smooth muscle actin and resident macrophages in the aortic sinus were also unaltered by either treatment vs. vehicle treated Apoe−/− HFD mice.ConclusionOur data show that prolonged administration of the KCa channel activator SKA-31 improved endothelial function without modifying fatty plaque formation in the aorta of Apoe−/− mice.
Unveiling the power of social influence: how functional, emotional, and social values drive Pilates participation through an extended TPB model
Authors: Kim Sukkyu , Jeong Yunduk , Jung Youngsu 
Published: February 2025

PurposeThis study investigates how functional, emotional, and social values shape Pilates participants’ attitudes and behavioral intentions within an Extended Theory of Planned Behavior (ETPB) framework.MethodA survey was conducted with 288 Pilates participants, and structural equation modeling was employed to analyze the relationships among perceived value, attitude, subjective norms, perceived behavioral control, and behavioral intention.ResultsThe findings indicate that functional and social values positively influence attitudes, whereas emotional value has no significant effect. Moreover, subjective norms exert the strongest influence on behavioral intention, highlighting the importance of social factors in Pilates participation.Discussion/conclusionThis study underscores the role of perceived value in shaping attitudes and confirms the dominant impact of subjective norms on behavioral intention. The findings offer theoretical contributions by refining the ETPB model and provide practical insights for enhancing engagement in Pilates programs.Originality/valueThis study contributes to the literature by applying an ETPB model to the context of Pilates, incorporating perceived value as an additional factor. It challenges the traditional emphasis on attitude as the primary predictor of behavioral intention by highlighting the dominant role of subjective norms. These insights offer a more nuanced understanding of the factors driving Pilates participation and provide practical implications for developing strategies to enhance engagement and retention in Pilates programs.
The impact of inequality on social value orientation: an eye-tracking study
Authors: Wang Qian-Hui , Wei Zi-Han , Chen Wan-Ning , Na Yu , Gou Hui-Ming , Liu Hong-Zhi 
Published: February 2025

IntroductionResearchers have developed the social value orientation (SVO) framework to describe prosocial tendencies. However, existing tools for measuring SVO lack sufficient attention to the effect of option inequality, driven by the inequality-aversion motive. In this research, we conducted an eye-tracking experiment to compare the traditional SVO measure with the inequality-controlled condition, investigating how it influences estimated SVO values and underlying process mechanisms.MethodsA within-subjects eye-tracking experiment was conducted with 65 university students recruited from a university’s human subjects pool. Participants received 20 yuan (RMB; approximately US $2.9) in cash for their participation.ResultsSVOs were lower in the inequality-controlled condition than in the traditional SVO measure. Information processing, including complexity, depth, and direction, differed when fairness was controlled. The predictive effect of relative time advantage was also enhanced under controlled inequality conditions. In addition, the predictive effect of relative time advantage was stronger when controlling for option inequality, suggesting that controlling for option inequality enhances bottom-up information processing.DiscussionThese findings suggest that traditional SVO measures may overestimate prosocial tendencies due to a lack of inequality control. The study highlights the role of fairness evaluation in SVO assessments and provides insights into the cognitive mechanisms underlying prosocial decision-making, offering guidance for future SVO measurements.
Exploring the interplay of mental health knowledge, stigma, and social distance among clinical nurses: a study in Liaoning, China
Authors: Wang Weiwei , Xia Junhong , Chen Wei , Ye Junhua , Xie Kun , Zhang Zhuona , Binti Mohamad Siti Mardhiana , Shuid Ahmad Naqib 
Published: February 2025

BackgroundStigma related to mental health conditions has a negative impact on both the nursing staff and their patients. Most of the current research on stigma explores the impact of single factors on stigma and does not explore the relationship between knowledge, social distance and stigma among clinical nurses.MethodsA convenience sampling method was used to conduct a questionnaire survey among 628 nurses from five hospitals in Liaoning Province in March 2021 and June 2021 using a combination of online and offline methods. To study the negative attitudes toward patients with mental illness among clinical nurses and to analyze the relationship between mental ill health stigma, social distancing, and mental health knowledge among nurses. The questionnaire includes Sociodemographic data, Scale for Assessing the Stigma of Mental Illness in Nursing (score range: 20~100, the higher the score, the less stigma attached to mental ill health), Mental Illness Social Distance Scale (score range: 6~30, the higher the score, the greater the social distance) and Mental Health and Mental Health Knowledge Questionnaire (score range: 0~25, the higher the score, the higher the knowledge level).ResultsThe nurses’ mental ill health stigma score was 58.96 ± 9.38 points, the mean scores of psychiatric and general nurses were 58.86 ± 9.33 and 59.41 ± 9.58 points, respectively. Willingness to become a psychiatric nurse is a factor influencing the stigma of mental illness. The stigma of mental ill health, social distance and mental health knowledge of nurses are positively correlated (P&lt;0.01). The mediation analysis demonstrated that mental health stigma significantly mediated the relationship between mental health knowledge and social distance (a= 0.599, P&lt;0.001; b= -0.194, P&lt;0.001). After accounting for stigma, the direct effect of mental health knowledge on social distance was no longer significant (c’=-0.007, P=0.078), highlighting the central role of stigma in this relationship.ConclusionsNurses mental ill health stigma is moderate and is the main mediating effect between mental health knowledge and social distancing. The pivotal role of mental health knowledge in shaping nurses’ attitudes and behaviors pertaining to social distancing in the context of mental illness. By combating stigma and enhancing mental health literacy among healthcare practitioners, we can foster environments that promote inclusive and compassionate care practices, thereby ameliorating patient outcomes and redressing disparities in mental health treatment.