bluuebunny/crossref_metadata_2025_split huggingface dataset:
Mass balance, metabolism, and pharmacokinetics of [14C]amdizalisib, a clinical-stage novel oral selective PI3Kδ inhibitor for the treatment of non-hodgkin’s lymphoma, in healthy Chinese volunteers
Authors: Zhao Chun-Yang , Zhang Li-Jun , Sun Chan , Yu Cheng-Yin , Wang Jian , Sai Yang , Su Wei-Guo , Chen Qian , Wang Wei , Jia Jing-Ying , Liu Gang-Yi , Liu Yan-Mei 
Published: November 2024

IntroductionAmdizalisib (HMPL-689) is an ATP-competitive PI3Kδ inhibitor currently under investigation for treating Hodgkin’s lymphoma. This study aimed to evaluate the metabolism, excretion, pharmacokinetics, and safety profile of amdizalisib in healthy human subjects to support its clinical application.MethodsThis Phase I clinical trial included six healthy Chinese male volunteers who received a single oral dose of 30 mg/100 µCi [14C]amdizalisib suspension. Blood, urine, and fecal samples were collected to analyze pharmacokinetics, metabolic pathways, and excretion patterns.ResultsAmdizalisib was rapidly absorbed, with a median Tmax of 2.5 h. The Cmax of 244 ± 48.9 ng/mL, and AUC0-t was 1870 ± 474 h ng/mL after a single oral dose. The blood-to-plasma total radioactivity ratio ranged from 0.561 to 0.645, indicating no significant affinity of [14C]amdizalisib and its metabolites to blood cells and the radioactive material is mainly distributed in plasma. Excretion was primarily via feces and urine, with 62.08% ± 3.00% and 37.15% ± 2.84% of the dose recovered, respectively, and over 94% of the drug excreted within 96 h. The parent drug was the main radioactive component in plasma (51.45% of total radioactivity). Additionally, 11 metabolites were identified, and the metabolic pathways include oxidation on the benzene or pyrimidine rings and conjugation with cysteine or glucuronic acid. The major metabolites in plasma were the di-oxidized and hydrogenated product (M424) and the mono-oxidized product (M406-2), accounting for 16.67% and 20.91%, respectively. Both of them are also the major radioactive components in urine and feces, among of which M424 accounted for 21.01% and 14.26%, M406-2 accounted for 8.08% and 11.30%, of the administered dose in urine and feces, respectively. In addition, the di-oxidized and methylated product (M436) was one of the major metabolites in feces accounting for 17.7% of the administered dose. Few of the parent drug was found in urine and feces, suggesting primary metabolized in the liver. No serious adverse events or drug-related deaths occured, with diarrhea as the most common adverse event.DiscussionThese findings demonstrate that amdizalisib is rapidly absorbed, extensively metabolized, and primarily excreted via feces and urine, supporting its continued development as a potential therapeutic for Hodgkin's lymphoma.Systematic Review Registration:https://www.chinadrugtrials.org.cn/, identifier CTR20212448.
Eleutheroside B alleviates oxidative stress and neuroinflammation by inhibiting the JAK2/STAT3 signaling pathway in a rat high altitude cerebral edema model
Authors: He Yacong , Zhang Hongying , Zhang Xiu , Han Yue , Duan Huxinyue , Song Wenqian , Tian Qingqing , Wang Yilan , Li Guang , Wu Chunjie , Wang Zhenxing , Zhao Tianzhu 
Published: November 2024

BackgroundHigh altitude cerebral edema (HACE) is a condition where the central nervous system experiences severe impairment as a result of sudden oxygen deprivation at high elevations. At present, effective measures for preventing and treating this condition are still lacking. Eleutheroside B (EB), the primary natural active compound found in the Eleutheroside senticosus, has demonstrated various biological functions. It has also shown significant potential in addressing acute mountain sickness and various neurological disorders. However, additional investigation is required to explore the potential protective effects and its underlying mechanisms of EB on HACE.MethodsThe male rats received pre-treatment with either vehicle, EB 100 mg/kg or 50 mg/kg, Dexamethasone 4 mg/kg, or coumermycin A1 100 μg/kg. To simulate the hypobaric hypoxia environment at a plateau of 6,000 m, a hypobaric hypoxia chamber was utilized. The therapeutic effects of EB were assessed through measurements of brain water content, histopathological observation, and evaluation of oxidative stress and inflammatory factors using immunofluorescence and ELISA. Furthermore, molecular docking, molecular dynamics simulation and Western blot were employed to clarify its molecular mechanism. Through these analyses, the underlying mechanism by which EB on HACE was identified.ResultsPre-treatment with EB demonstrated a significant protective effect against HACE by effectively reducing brain water content, down-regulating HIF-1α and AQP4 protein expression induced by hypoxia and reversing pathological changes in brain tissue and neuron damage. Compared to the group treated with HACE alone, the group pre-treated with EB showed a significant reduction in levels of ROS and MDA, as well as an increase in GSH. In addition, pre-treatment with EB led to a significant decrease in the levels of IL-1β, IL-6, and TNF-α. Molecular docking and dynamics simulations indicated that EB has a strong binding affinity to the JAK2/STAT3 signaling pathway. Western blot further confirmed that EB significantly downregulated the expression of JAK2/STAT3 related proteins in the brain tissue of HACE rats. Additionally, coumermycin A1, an agonist of the JAK2, reversed the anti-oxidative stress and neuroinflammation against HACE of EB.ConclusionEB exerts its antioxidant stress and anti-neuroinflammatory effects by inhibiting the JAK2/STAT3 signaling pathway in a rat HACE model.
Six weeks of polarized functional interval training with large training load reductions does not affect performance gains compared to traditional workouts
Authors: Held Steffen , Isenmann Eduard , Rappelt Ludwig , Wiedenmann Tim , Kutschki Dominic , Harbrecht Jannik , Kirchner Katrin , Geisler Stephan , Donath Lars 
Published: November 2024

PurposeHigh-intensity functional interval training (HIFT) is predominantly composed of high exercise training intensities (HiT) and loads. Both have been linked to a higher risk of overtraining and injuries in inexperienced populations. A polarized training approach is characterized by high amounts of low-intensity training (LiT) and only approximately 5%–20% HiT. Compared to HIT-based training, this approach can result in temporary training load and intensity reductions without diminishing training gains. Thus, we aimed to examine the effects of traditional (TRAD) HIFT vs. polarized (POL) HIFT on relevant performance parameters.MethodsThirty athletes (15 females, age: 26.6 ± 5.0 years, height: 1.76 ± 0.13 m, body mass: 79.6 ± 12.4 kg, prior experience: 2.3 ± 2.0 years, training volume: 6.1 ± 2.4 h/wk) were randomly assigned to 6 weeks of either POL (78% LiT, 22% threshold intensity training (ThT) to HiT) or TRAD (26% LiT, 74% ThT to HiT). HIFT performance testing focused on maximal strength (squat: SQ1RM, deadlift: DL1RM, overhead press: OHP1RM, high pull: HP1RM), endurance (peak oxygen uptake: V̇O2peak, lactate threshold: LT, peak power output (PPO), and benchmark HIFT workout (Jackie: 1000 m rowing, 50 thrusters, and 30 pull-ups for time).ResultsPOL (785 ± 71 au) completed significantly (p ≤ 0.001; SMD = 4.55) lower training load (eTRIMP) than TRAD (1,273 ± 126 au). rANCOVA revealed no statistical relevant group×time interaction effects (0.094 ≤ p ≤ 0.986; 0.00 ≤ ηp2 ≤ 0.09) for SQ1RM, DL1RM, OHP1RM, high pull, V̇O2peak, LT, PPO, and Jackie performance. Both groups revealed trivial to moderate but significant (rANCOVA time effects: p ≤ 0.02; 0.01 ≤ ηp2 ≤ 0.11; 0.00 ≤ SMD ≤ 0.65) performance gains regarding DL1RM, OHP1RM, HP1RM, and Jackie.ConclusionDespite a notably lower total training load, conditioning gains were not affected by a polarized functional interval training regimen.
Evaluating rice lipid content, yield, and quality in response to nitrogen application rate and planting density
Authors: Chen Guangyi , Li Congmei , Hu Mingming , He Xingmei , Yang Hong , Zhang Qiuqiu , Wu Chaoyue , Duan Qiang , Peng Ligong , Zhang Yao , Li Ziyu , Ouyang Yuyuan , Lan Yan , Li Tian 
Published: November 2024

To investigate the effects of nitrogen (N) application rate and planting density (D) on the contents of lipid and free fatty acid, fatty acid composition, yield and quality of rice grain, a field experiment was conducted using Koshihikari (japonica) as experimental material from 2021 to 2022 with three N levels (90, 150 and 210 kg ha-1, denoted as N1, N2 and N3, respectively) and three transplanting densities (19.0 × 104, 26.7 × 104 and 40.0 × 104 plants ha-1, denoted as D1, D2 and D3, respectively). The results showed that N application rate and planting density had highly significant impacts only on the contents of free fatty acid and saturated fatty acid, respectively. Increased N and planting density enhanced the contents of lipid (29.41 mg g-1) and free fatty acid (21.47%). The highest values were obtained under N3D3 increasing by 7.02% and 3.23 percentage points, respectively, compared to other treatments. No significant differences in lipid content were found among treatments, whereas free fatty acid exhibited significant differences. The unsaturated fatty acid content increased with increasing N but first decreased and then increased with increasing planting density, while saturated fatty acid content showed the opposite trend. Appropriate N level and planting density improved the relative chlorophyll content and net photosynthetic rate of rice flag leaves, as well as increased grain yield, effective panicle number and spikelete number per panicle, but decreased the seed setting rate. Under N2D2, the relative chlorophyll content and net photosynthetic rate remained relatively high throughout the grain filling stage, resulting in the highest grain yield, with increases of 43.87-47.03% compared to other treatments. A moderate N level improved the milling quality of rice, while increased planting density reduced it. However, both increased N and planting density reduced the appearance quality and cooking and eating quality of rice. Overall, the effects of increasing N application rate and planting density on enhancing rice lipid and free fatty acid contents were limited. A combination of 150 kg ha-1 N application rate and 26.7 × 104 plants ha-1 was recommended for achieving relatively higher yield, lipid content and better grain quality.
Change in self-construal: a repertory grid technique study of women admitted to a Mother and Baby Unit
Authors: Wozniak Eleanor E. , Hare Dougal Julian , Gregg Lynsey , Wittkowski Anja 
Published: November 2024

IntroductionPregnancy and the postnatal period represent a time of heightened risk for women to experience mental health difficulties. Some mothers may require specialist inpatient psychiatric support made available through Mother and Baby units (MBUs). Although there is evidence of the therapeutic benefits of MBUs, many studies have utilised methodologies vulnerable to interviewer and social desirability biases. The repertory grid technique (RGT), derived from personal construct theory (PCT), has been successfully used to explore how the way in which a person thinks about and defines the self (i.e., self-construal) changes following therapeutic intervention in samples of people experiencing mental health conditions. Therefore, this study aimed to explore change in maternal self-construal following MBU admission, utilising the RGT, thereby enhancing our understanding for the therapeutic role of MBU admissions in women’s mental health recoveries.MethodsParticipants were recruited from two MBUs in England. RGT was undertaken with participants shortly after admission and again at discharge, allowing for comparisons between grids to assess change in how a mother viewed herself in relation to certain aspects of the self (e.g., ideal self) and other people, a concept referred to as construing in PCT. Data were analysed using principal component analysis, Slater analysis, and content analysis.ResultsThere were 12 participants who completed repertory grids at admission, with eight (66.67%) participants also completing discharge grids. Most of the eight participants demonstrated improvements in overall self-esteem and self-esteem as a mother, a shift towards a more positive self-perception, and increased construed similarity between the self and positively construed others, and construing became more varied. Conversely, a few participants displayed a reduction in self-esteem, particularly in the maternal role and increased construed similarity between the self and negatively construed others, and construing became more rigid.ConclusionsAll participants exhibited changes to construing during their MBU admission, with most participants displaying positive changes to self-esteem and self-perception and a more adaptive process of construing. Potential implications are offered for service users, families, clinicians, and stakeholders. Recommendations for future research are also provided.
Exploring how children and adolescents talk about coping strategies relating to loneliness using reflexive thematic analysis: a qualitative study
Authors: Burke Lauren , Verity Lily , Riddleston Laura , Fuhrmann Delia , Qualter Pamela , Lau Jennifer Y. F. , Demkowicz Ola 
Published: November 2024

IntroductionThe prevailing view is that loneliness predominantly affects older adults. However, awareness of high rates of loneliness among younger populations is growing, prompting a call for interventions. The current study aimed to listen to the voices of young people regarding how they cope with loneliness, gaining a better understanding of how to then develop tailored interventions.MethodsThirteen Arts-based focus groups were conducted with 74 participants (8-18 years old), in London, Manchester, and South Yorkshire. Reflexive thematic analysis was utilised.ResultsWe developed six themes as follows: (1) “Determinants of the coping approach for loneliness”, (2) “Considerations to guide decision making”, (3) “Coping strategies to alleviate loneliness”, (4) “Social connection as a coping strategy for loneliness – considerations”, (5) “Being active in your own coping success”, and (6) “Worsening loneliness, coping strategies gone wrong”.ConclusionsParticipants described a partially sequential process in choosing coping strategies for loneliness, including effective and maladaptive choices. Effective strategies were highlighted, reflecting developmental stages with the need for self-motivation. Participants noted challenges in engaging in coping due to skill deficits. These findings are crucial for developing interventions specific to this population.
The epidemiology of road traffic injuries in the republic of Serbia: a study based on hospital data, 2015-2019
Authors: Rajčević Smiljana , Štrbac Mirjana , Kukić Dragoslav , Marković Marija , Ivanović Ivan , Petrović Radmila , Radić Ivana 
Published: November 2024

IntroductionRoad traffic injuries (RTI) are the leading cause of death and severe disability among individuals under the age of 40, posing a significant public health challenge globally. This manuscript highlights key aspects of the epidemiology of injuries in road traffic crashes (RTC) in Serbia, based on hospitalization report data.ObjectivesThe main aim of this study was to analyze the epidemiological characteristics of road traffic injuries (RTI) based on hospital data over a five-year period in Serbia.MethodsThe data for this study were obtained from the Hospitalization Report, which is part of the hospitalization database maintained by the Institute for Public Health of Serbia “Dr Milan Jovanović Batut,” covering the period from January 2015 to December 2019. The research included data from the Hospitalization Reports of 66 healthcare institutions across Serbia.ResultsDuring the study period, a total of 15,028 patients with road traffic injuries were admitted to healthcare institutions in Serbia. During the five-year period, the crude RTI incidence rate increased every year, from 39.0/100, 000 in 2015 to 43.7/100,000 in 2019. Older adult people aged 65 and over were particularly vulnerable as bicyclists and pedestrians (31.3, 27.7%, respectively). The Vojvodina region experienced a higher incidence of injuries among bicyclists compared and car accidents were most frequent in Central Serbia than in the other regions of Serbia. Craniocerebral injuries were the most common type of road traffic injury, accounting for 37.8% of cases. Significant differences in the types of injuries were observed based on age (χ2 = 649.859; p &lt; 0.001) and gender (χ2 = 31.442; p &lt; 0.001).ConclusionUnderstanding the epidemiological profile of road users involved in accidents is essential for monitoring and controlling specific risk factors. Our results highlight the need for enhanced traffic safety measures at the local level.
Evaluation of the osteoarthritis disease burden in China from 1990 to 2021: based on the Global Burden of Disease Study 2021
Authors: Liang Jiahui , Wang Yue , Yu Fei , Jiang Guichun , Zhang Weiguo , Tian Kang 
Published: November 2024

ObjectiveThis study aims to understand the current status and trend of the disease burden of osteoarthritis (OA) in people over 30 years old in China from 1990 to 2021 and identify the priority population groups, to provide reference data for the prevention and treatment of OA in China.MethodsThe Global Burden of Disease Study 2021 was used to describe the incidence, prevalence, and disability-adjusted life years (DALYs) of OA in adult aged 30 years or older in China by sex and age groups, which was used to analyze the disease burden of OA from 1990 to 2021. The joinpoint regression model and age-period-cohort model were used to characterize the temporal trend.ResultsIn 2021, the number of OA prevalence in China was about 152.85 million, and the number of incidences was about 11.65 million. The age-standardized prevalence rate (ASPR), age-standardized incidence rate (ASIR) and age-standardized DALYs rate (ASDR) of OA in China are lower than those in developed countries such as Korea, the United States of America and Japan, but higher than those in India. Knee osteoarthritis had the highest ASPR and ASDR. The highest incidence rate was 50–54 years, and the highest prevalence and DALYs rate were in the age group of patients over 95 years old. The incidence rate of women in all age groups is higher than that of men. From 1990 to 2021, the ASIR, ASPR and ASDR of OA in China roughly showed an increasing trend year by year. The age-period-cohort analysis showed that the peak age groups for longitudinal age incidence of OA in China from 1992 to 2021 were 50–54 years and 80–84 years. We found that the OA incidence was highest in the period 2017–2021.ConclusionThe disease burden of OA in those over 30 years old in China from 1990 to 2021 will become more and more serious, and the target population for primary prevention is the female population under 50 years old. The development of a scientific and effective comprehensive prevention and treatment program for OA is imminent.
Exploring relationships between dating app use and sexual activity among young adult college students
Authors: Reeves Jaquetta M. , Griner Stacey B. , Johnson Kaeli C. , Jones Erick C. , Shangani Sylvia 
Published: November 2024

BackgroundUniversity campus clinics provide crucial sexual health services to students, including STI/HIV screening, testing, contraception, and counseling. These clinics are essential for engaging young adults who may lack access to primary care or have difficulty reaching off-campus services. Dating apps are widely used by young adults, yet there is a lack of studies on how they affect sexual practices. This study aimed to evaluate the use of dating apps, engagement in condomless sexual activity, and the prevalence of STIs among young adult college students in Northern Texas.MethodsA cross-sectional survey was conducted from August to December 2022 among undergraduate and graduate students aged 18–35 at a large university in Northern Texas. A total of 122 eligible participants completed the survey, which assessed demographics, sexual behaviors, dating app use, and STI/HIV testing practices. Descriptive statistics, bivariate analyses, and multivariate Poisson regression analyses with robust variance were performed to identify factors associated with dating app use and condomless sexual activity.ResultsTwo-thirds of participants reported using dating apps. Significant differences were found between app users and non-users regarding demographic factors and unprotected sexual behaviors. Dating app users were more likely to report multiple sexual partners, inconsistent condom use, and a higher likelihood of engaging in unprotected sex. Poisson regression analysis indicated that app use was associated with residing in large urban areas, frequent use of campus STI/HIV screening services, and having multiple sexual partners (p &lt; 0.05).ConclusionThe study highlights a significant association between dating app use and engagement in condomless sexual activity among college students. University health clinics play a critical role in providing sexual health services and can enhance their impact by expanding access to testing, contraception, and inclusive, sex-positive education. Future research should explore the long-term effects of dating app use on sexual health and evaluate the effectiveness of app-based interventions in promoting safer sexual practices.
Mental preparation in runners: gender differences, competition levels, and psychological training effects on performance
Authors: Kelemen Bence , Tóth Renátó , Benczenleitner Ottó , Tóth László 
Published: November 2024

IntroductionThe present study aimed to investigate the mental and sports psychological preparation, as well as tactical preparation, of distance runners for competition. We examined whether there are differences based on gender, competition level and various race disciplines, as well as how mental preparation influences sports skills applicable in different competitive situations.MethodsThe sample consisted of 201 distance runners who completed the Sports Mental Training Questionnaire (SMTQ) alongside assessments of their sports psychology and race tactics.ResultsThe results indicated that neither gender, competition level, nor race discipline had a significant impact on mental preparedness. However, women demonstrated notably higher scores in the use of self-talk as a mental technique. Additionally, participants who received training in sports psychology scored significantly higher across several mental skills, as well as on the overall mental preparedness score.DiscussionThis article validates the SMTQ and its association with mental readiness, as confirmatory factor analysis demonstrates adequate validity. Additionally, mental preparation was found to enhance performance and well-being among distance runners. Further research is needed to explore the impact of group interventions to broaden the reach of mental training programs.