bluuebunny/crossref_metadata_2025_split huggingface dataset:
Immune-related adverse events with PD-1/PD-L1 inhibitors: insights from a real-world cohort of 2523 patients
Authors: Yan Ting , Long Minghui , Liu Chaoyi , Zhang Jiwen , Wei Xingyu , Li Fei , Liao Dehua 
Published: January 2025

PurposeImmune checkpoint inhibitors (ICIs) have significantly changed cancer therapy, improving patient survival rates and clinical outcomes. Nevertheless, the use of PD-1/PD-L1 inhibitors can result in immune-related adverse events (irAEs). This study aims to investigate the prevalence and associated risk factors of irAEs in a real-world setting, as well as to assess their effects on optimal therapeutic outcomes.MethodsA retrospective analysis involved 2523 patients with cancer who received inpatient PD-1/PD-L1 inhibitors treatment between January 2018 and December 2022. We documented patients’ demographic and clinical characteristics, PD-1 or PD-L1 inhibitors, treatment modalities, incidences, timing, and severity of irAEs, and efficacy outcomes by reviewing inpatient records. Patients were categorized into an irAEs group and a non-irAEs group, with the former further subdivided into a multiple irAEs group and a single irAE group. Chi-square tests were employed to evaluate differences in baseline characteristics and efficacy outcomes between the irAEs and non-irAEs groups, as well as between the multiple and single irAE groups. Additionally, logistic regression analysis was utilized to identify risk factors linked to irAEs.ResultsAmong 2523 eligible patients, 1096 reported 1802 irAEs, with an incidence incidence of 43.4%. Among 1096 individuals, 92.1% were classified as grade 1–2, while 7.9% were grade 3 or higher. IrAEs affected various organ systems, with endocrine toxicity (17.7%), hepatic toxicity (17.2%), and hematologic toxicity (11.4%) being the most common. 20.5% patients experienced multi-system irAEs. The average time for patients to develop irAEs was within four treatment cycles. Significant differences in patient gender, age, Eastern Cooperative Oncology Group (ECOG) Performance Status (PS), comorbidities, PD-1 or PD-L1 inhibitors, and treatment modalities were observed between the irAEs and non-irAEs groups, but not between the multiple irAEs and single irAE groups. Compared to the non-irAEs group, the irAEs group exhibited a higher objective response rate (ORR) and disease control rate (DCR), and the multiple irAEs group also showed a higher ORR than the single irAE group.ConclusionThis real-world study indicated that the occurrence of irAEs is related to patient gender, age, ECOG PS, comorbidities, PD-1/PD-L1 inhibitors, and treatment modalities. The occurrence of irAEs may be associated with better treatment benefits.
Rat perivascular adipose tissue microvasculature revealed by tissue clearing
Authors: Watts Stephanie W. , Flood Emma , Gulbransen Brian D. , Jackson William F. 
Published: January 2025

Perivascular adipose tissue (PVAT) surrounds the majority of blood vessels and plays diverse roles in vascular and metabolic functions. The hormonal and lipid exchange functions of PVAT require access to blood vessels. However, the microvascular supply of PVAT, especially in rats, remains enigmatic due to technical restraints involved in imaging fat depots. Therefore, we developed and validated an approach to visualize the microvasculature of PVAT in rats. In this study, we report a stepwise protocol as a method to clear and visualize the microvasculature of the thoracic aortic PVAT in the Dahl salt-sensitive (SS) rat. Blood vessels are first traced in anesthetized rats using Lycopersicon esculentum (tomato) lectin DyLight 649 (Lectin 649). The dissected aorta with intact PVAT is then subjected to a stepwise clearing protocol over 12 days, followed by imaging on a Nikon confocal microscope. Images were stitched together to visualize cross sections of the whole vessels. The microvasculature of aortic PVAT is present and profoundly dense, and it is similar in the ventral and lateral lobes of aortic PVAT. This developed method is adoptable and adaptable to other PVATs in rats.
Effects of Eleclazine (GS6615) on the proarrhythmic electrophysiological changes induced by myocardial stretch
Authors: Chorro Francisco J. , Such-Miquel Luis , Cuñat Samuel , Arias-Mutis Oscar , Genovés Patricia , Zarzoso Manuel , Alberola Antonio , Such-Belenguer Luis , Del Canto Irene 
Published: January 2025

PurposeMyocardial stretch is a proarrhythmic factor. Eleclazine (GS6615) is a late sodium current (INaL) inhibitor that has shown protective effects against arrhythmias in various experimental models. Data on its effects during myocardial stretch are lacking. The aim of this study was to investigate the electrophysiological modifications induced by eleclazine basally and during acute ventricular stretch.MethodsLeft ventricular stretch was induced at baseline and during perfusion with eleclazine in 26 Langendorff rabbit heart preparations. Programmed stimulation and high-resolution mapping techniques were applied using multiple epicardial electrodes.ResultsAt baseline, both the ventricular refractory period measured at a fixed cycle length (250 m) and its surrogate obtained during ventricular fibrillation (VF) decreased significantly during stretch (baseline 128 ± 15 vs. stretch 110 ± 14 m; n = 15; p &lt; 0.001, and baseline 52 ± 13 vs. stretch 44 ± 9 m; n = 11; p &lt; 0.05), while the VF dominant frequency (DF) increased significantly (DF baseline 13 ± 3 vs. stretch 17 ± 5Hz; n = 11; p &lt; 0.01). Eleclazine 1.4 μM prolonged refractoriness, diminished both DF and conduction velocity during the arrhythmia, and avoided the stretch induced variations in refractoriness (baseline 148 ± 19 vs. stretch 150 ± 23 m; n = 15; ns, and baseline 73 ± 15 vs. stretch 77 ± 15 m; n = 11; ns) and in DF (baseline 12 ± 5 vs. stretch 12 ± 3 Hz; ns). The VF complexity index was inversely related to refractoriness (r = −0.64; p &lt; 0.001). Under eleclazine perfusion, the VF activation patterns were less complex, and the arrhythmia stopped in 6 out of 11 experiments (55%; p &lt; 0.05 vs. baseline).ConclusionEleclazine (GS6615) reduced the proarrhythmic electrophysiological changes induced by myocardial stretch and slowed and simplified activation patterns during VF in the experimental model used.
Inducing salt stress tolerance in bitter gourd (Momordica chanrantia) through seed treatment with chitosan
Authors: Ali Ahsan , Ferdosi Fiaz Hussain , Sarwar Mubeen , Anjum Sumreen , Mushtaq Zain , Liaquat Mehwish , Abbas Muhammad Taqqi , Anees Moazzam , Tariq Muhammad Rizwan , Ashraf M. Irfan , Alasmari Abdulrahman , Mondol Md Sabir Ahmed , Abdi Gholamreza 
Published: January 2025

BackgroundBitter gourd requires well-drained sandy to sandy loam soils for optimum growth, development, and germination, while its growth is retarded in extreme saline conditions. It is very sensitive to salinity stress, which imposes devastating limits on its productivity. Thus, the impact of soil salinization on the economics of bitter gourd yield deserves scientific inquiry. MethodsThe present study was designed to evaluate the various morphological attributes (mean germination time, germination index, final emergence percentage, measurements of root length, measurement of shoot length, measurement of plant dry biomass, and measurement of plant fresh biomass), physiological attributes (leaf chlorophyll content and electrolyte leakage), biochemical attributes (proline contents, antioxidant enzymes, superoxide dismutase, catalase Q9 , and peroxidase), leaf water relations (leaf osmotic potential, leaf water potential, leaf turgor potential, and leaf relative water content), and ion concentrations (Na+, K+, Ca +, and Cl-) that can be used for the evaluation of salt stress tolerance potential in bitter gourd. The research was conducted in the field area of the Faculty of Agricultural Sciences, University of the Punjab, Lahore. ResultsIn this experiment, bitter gourd seeds were sowed either without treatment or with hydropriming, 0.01%, 0.02%, 0.03%, 0.04%, and 0.05% chitosan, respectively, under 50mM soil salinity under the climatic conditions of Lahore. This research was designed to find the role of chitosan in inducing salt stress tolerance in bitter gourd plants and also find the best chitosan dose that is useful for higher salinity conditions. Different attributes of bitter gourd were recorded. Results revealed that chitosan application at 0.04% is best for enhancing the salt stress tolerance potential of bitter gourd. Different morphological attributes, physiological attributes, water relation attributes, and biochemical parameters were also recorded. It was observed that pre-sowing treatments with an optimized dose of 0.04% chitosan exhibited significant effects on all the bitter gourd plants and improved the germination rate by improving the salt stress tolerance potential of plants under high salinity. ConclusionIt can be concluded from the present research that the optimized dose of 0.04% chitosan has also proved effective in the enzymatic activity of bitter gourd by enhancing the salt stress potential under increasing salt stress.
Integrated physiological and transcriptomic analysis uncovers the mechanism of moderate nitrogen application on promoting the growth and (-)-borneol accumulation of Blumea balsamifera
Authors: Yuan Yuan , Tang Wei-Jie , Cao Jia-Yuan , Zhong Ke , Mo Ze-Jun , Zhou Ying , Pang Yu-Xin 
Published: January 2025

IntroductionBlumea balsamifera, a half-woody plant belonging to the Asteraceae family, is valued as both a medicinal and industrial crop primarily for its phytochemical component, (-)-borneol. Nitrogen (N) is essential for regulating the growth of B. balsamifera and the biosynthesis of (-)-borneol; however, the molecular mechanisms by which N influences these processes remain inadequately understood. This study aimed to elucidate the effects of N on growth and (-)-borneol synthesis at the molecular level.MethodsA field experiment was conducted in which B. balsamifera plants were fertilized with three different nitrogen regimes: 0 kg N ha-1 (control, CK), 150 kg N ha-1 (N1 treatment), and 300 kg N ha-1 (N2 treatment). Physiological and biochemical assessments were performed to evaluate the growth and metabolic responses of the plants under these varying N conditions. Additionally, transcriptome sequencing of leaves of B. balsamifera was conducted to elucidate the underlying molecular mechanisms involved.Results and discussionThe results indicated that both the N1 and N2 treatments significantly promoted the growth of B. balsamifera, with the 150 kg N ha-1 treatment (N1) resulting in the most favorable effects. Under the N1 treatment, the leaves harvested in October, November, and December exhibited the highest accumulation of (-)-borneol, with yields of 782 mg plant-1, 1102 mg plant-1, and 1774 mg plant-1, respectively, which were significantly different from those observed in the CK and N2 treatments. Comparative transcriptome analysis revealed a total of 6,714 differentially expressed genes (DEGs). Notably, several DEGs associated with auxin signaling and N metabolism were upregulated in the N1 and N2 treatments. In contrast, many DEGs related to carbohydrate metabolism, terpenoid backbone biosynthesis, monoterpenoid biosynthesis, and flavonoid biosynthesis were significantly upregulated in the CK treatment. Moreover, potential transcription factors (TFs) that may link N nutrition with the synthesis of medicinal components were identified. Our study demonstrates that N can enhance the accumulation of (-)-borneol in B. balsamifera when applied in appropriate quantities. These findings provide a comprehensive understanding of the relationship between N nutrition and (-)-borneol yield in B. balsamifera, offering valuable insights for future cultivation practices.
Physiological and molecular mechanisms of exogenous salicylic acid in enhancing salt tolerance in tobacco seedlings by regulating antioxidant defence system and gene expression
Authors: Song Xiliang , Chen Jian , Xu Can , Cai Xianjie , Song Wenjing , Chang Aixia , Zhang Yu , Luo Chenggang 
Published: January 2025

IntroductionSalt stress has emerged as a predominant abiotic factor that jeopardizes global crop growth and yield. The plant hormone salicylic acid (SA) has notable potential in mitigating salt toxicity, yet its mechanism in enhancing the salinity tolerance of tobacco plants is not well explored.MethodsThis study aimed to assess the potential benefits of exogenous SA application (1.0 mM) on tobacco seedlings subjected to saline soil conditions.ResultsThe foliar spray of SA partially mitigated these salt-induced effects, as evidenced by a reduction of malondialdehyde content, and improvements of leaf K+/Na+ ratios, pigment biosynthesis, and electron transport efficiency under NaCl stress. Additionally, SA increased the contents of total phenolic compound and soluble protein by 16.2% and 28.7% to alleviate NaCl-induced oxidative damage. Under salt stressed conditions, the activities of antioxidant enzymes, including superoxide dismutase, ascorbate peroxidase, catalase, and peroxidase increased by 4.2%~14.4% in SA sprayed tobacco seedlings. Exogenous SA also increased ascorbate and glutathione levels and reduced their reduced forms by increasing the activities of glutathione reductase, ascorbate peroxidase, monodehydroascorbate reductase and dehydroascorbate reductase. qRT−PCR analysis revealed that the key genes regulating SA biosynthesis, carbon assimilation, the antioxidant system and the ascorbate−glutathione cycle were activated by SA under conditions of salt stress.DiscussionOur study elucidates the physiological and molecular mechanisms of exogenous SA in enhancing plant salt tolerance and provides a practical basis for crop improvement in saline environments.
Relationship between accelerometer-measured physical activity and depressive symptoms in hemodialysis patients with comorbid diabetes mellitus: a multicenter cross-sectional study
Authors: Liang Ruiting , Chen Xiaoyu , Siqin Gaowa , Zhang Zhixin , Zhang Shumei , Li Lihua , Talin SarNa , Guo Qi 
Published: January 2025

ObjectiveThe objective of this study was to examine the association between accelerometer-derived moderate-to-vigorous physical activity (MVPA) and depressive symptoms in hemodialysis patients with and without type 2 diabetes mellitus (T2DM).MethodsThis cross-sectional study finally included 450 maintenance hemodialysis patients (male 281, average age 62 years) from seven dialysis centers in Shanghai, China. Physical activity (PA) was measured using the triaxial accelerometer (ActiGraph GT3X+, Pensacola, FL, United States). We measured depressive symptoms using the 9-item Patient Health Questionnaire (PHQ-9) (PHQ-9 ⩾ 10). We categorized physical activity into quartile groups (Q1 through Q4), with the first quartile defined as low engagement and the remaining quartiles defined as moderate to high engagement. We used logistic regression and trend test to analyze the relationship between quartile groups and depressive symptoms. The analyses in this study adjusted for a range of confounders.ResultsThe prevalence of depression was higher in patients with hemodialysis combined with T2DM (17.2%). In diabetic patients, MVPAQ4 was negatively associated with depression after adjusting for covariates [OR = 0.076; 95% confidence interval (CI) = 0.006–0.955, p = 0.046]. However, in non-diabetic hemodialysis patients, no significant association was found between MVPAQ1-Q4 and depression after adjusting for covariates (p &gt; 0.05).ConclusionModerate-to-vigorous physical activity was associated with depression in the diabetic hemodialysis group, but not in the non-diabetic group. Further studies are needed to investigate more causal relationships between MVPA and depressive symptoms in patients with T2DM.
Goal and shot prediction in ball possessions in FIFA Women’s World Cup 2023: a machine learning approach
Authors: Iván-Baragaño Iyán , Ardá Antonio , Losada José L. , Maneiro Rubén 
Published: January 2025

IntroductionResearch in women’s football and the use of new game analysis tools have developed significantly in recent years. The objectives of this study were to create two predictive classification models to forecast the occurrence of a shot or a goal in the FIFA Women’s World Cup 2023 and to identify the associated technical-tactical indicators to these outcomes.MethodsA total of 2,346 ball possessions were analyzed using an observational design, mapping two different target variables (Success = Goal and Success2 = Goal or Shot) with a relative frequency of 1.28 and 8.35%, respectively. The predictive capacity was tested using Random Forest and XGBoost and finally and SHAP values were calculated and visualized to understand the influence of the predictors.ResultsRandom Forest technique showed greater efficacy, with recall and sensitivity above 93% in the resampled dataset. However, recall on the original test sample was 13% (Success = Shot or Goal) and 0% (Success = Goal), demonstrating the models’ inability to predict rare events in football, such as goals. The indicators with the greatest influence on the outcome of these possessions were related to the possession zone, attack duration, number of passes, and starting zone, among others.ConclusionThe results highlight the need to incorporate a greater number of predictive variables in the models and underline the difficulty of predicting events such as goals and shots in women’s football.
Where you live, what you do: depression differences among diverse Chinese nongmin through cognitive openness
Authors: He Li , Wang Jiangyin , Yang Yang , Tian Zhilu , Jiang Liu 
Published: January 2025

ObjectiveThis study aims to investigate the depression levels among Workers with Agricultural Hukou (WAH) in China, considering their varied living environments, types of work, and social discrimination experiences. It specifically addresses the research question: Is there a significant discrepancy in depression levels among different subgroups within WAH?MethodsThe study utilizes data from the China Family Panel Studies (CFPS) for the years 2018 and 2020. To estimate the depression levels and their variances across different WAH subgroups, we employed three analytical methods: Ordinary Least Squares, Propensity Score Matching, and Two-Stage Least Squares.ResultsOur findings indicate that all WAH subgroups experience higher levels of depression compared to Workers with Non-Agricultural Hukou (WNAH). Among the WAH subgroups, the depression levels, in ascending order, are observed in Rural-to-Urban Migrant Workers (RUMW), Rural Non-Agricultural Workers (RNAW), Subsistence Farmers, and Agricultural Laborers. Notably, these differences in depression levels may be influenced by the mechanism of cognitive openness.ConclusionThe study concludes that there are significant disparities in depression levels among WAH subgroups. Understanding these differences is crucial for targeted mental health interventions and for addressing the broader implications of social discrimination and work-related stress among agricultural workers in China.
Comparative effects of methamphetamine, cannabis, and polysubstance use on oral health
Authors: Kılıç Osman Hasan Tahsin , Kürklü Arpaçay Duygu , Gezen Onur Çağdaş , Bayram Zehra Nur , Başer Aysel 
Published: January 2025

IntroductionThis study aimed to compare the clinical oral health status of individuals with Methamphetamine (MA), Cannabis (THC), and Polysubstance (PS) use disorders to healthy controls, and assess the impact of substance type, usage duration, quantity, and oral health behaviors on dental health outcomes through comprehensive oral examinations.MethodsThis cross-sectional clinical study was conducted at İzmir Democracy University Buca Seyfi Demirsoy Education and Research Hospital between April 2024 and August 2024. A total of 190 individuals with substance use disorders (MA, THC, and PS users) and 91 healthy controls participated. Sociodemographic data, substance use history, and oral health behaviors were collected using a researcher-developed questionnaire and the Turkish version of the Hiroshima University Dental Behavior Inventory (HU-DBI). Oral health status was assessed through clinical oral examinations using the Decayed, Missing, and Filled Teeth (DMFT) index. Statistical analyses were performed using SPSS 26.0, applying t-tests, ANOVA, Chi-square tests, and Pearson correlation to evaluate group differences and relationships between variables. A p-value of &lt; 0.05 was considered statistically significant.ResultsThe study revealed significant differences in oral health among substance users compared to the control group. MA users had the highest DMFT scores (11.04 ± 5.56), followed by THC users (9.49 ± 5.87), and PS users (8.40 ± 4.52), with the control group showing the lowest scores (6.08 ± 4.18) (p&lt;0.001). The study also found a moderate positive correlation between MA use and DMFT scores, indicating that longer and higher usage leads to poorer oral health, while no significant association was observed between THC use and DMFT scores. Additionally, significant disparities in education levels were observed, with substance users having lower education compared to controls (p=0.001). HU-DBI scores indicated poorer oral health behaviors in substance users, though the difference was not statistically significant (p=0.053).DiscussionThe study reveals that all substance use groups, including MA, THC, and PS users, exhibit significantly poorer oral health outcomes, with higher DMFT scores and worse oral health behaviors compared to the control group, highlighting the critical need for comprehensive dental care interventions for individuals with substance use disorders.Clinical Trial Registrationhttps://clinicaltrials.gov/study/NCT06640712, identifier NCT06640712.
Impact of online health education on attention-deficit/hyperactivity disorder screening results and parenting stress among school-aged children
Authors: Tan Jing , Yi Wenxia , Shen Jianna , Peng Bin , Gong Min , Li Feng , Chen Li 
Published: January 2025

AimsTo investigate the effects of an online health education lecture on the positive screening rate of attention-deficit/hyperactivity disorder (ADHD) and parenting stress among parents of children diagnosed with or screened positive for ADHD.MethodsUsing stratified proportional random cluster sampling, 14 primary schools in Chongqing were selected to conduct an online lecture about ADHD for parents and teachers. A total of 2,611 questionnaires were collected (1,508 intervention group, 1,103 control group).ResultsThe lecture did not significantly affect the positive screening rate of ADHD (parents: β=-0.37, p=0.208; teachers: β=0.53, p=0.338); however, the positive screening rate increased post-intervention. Inattention scores were higher in the intervention group (β=0.42, p=0.040). Parents as primary caregivers were associated with lower ADHD symptom scores (β=-0.61, p=0.022). Lower parental education levels were associated with higher ADHD screening rates (β=0.49, p=0.039) and symptom scores (β=0.60, p=0.022). Teachers with 10-19 years of experience had higher positive screening rates (β=1.26, p=0.005) and symptom scores (β=2.60, p&lt;0.001). The intervention did not affect parenting stress (Z=-1.413, p=0.158).ConclusionsThe lecture’s effects were relatively weak, using questionnaires may have facilitated health communication. Individual characteristics of parents and teachers should be considered in assessments (ClinicalTrial.gov ID: NCT05231902).