METHODS: HRD status was determined using the ACTHRD assay, an enrichment-based targeted next-generation sequencing assay. PD-L1 expression was assessed by SP263 immunohistochemistry assay. PD-L1 expression positivity was defined by the PD-L1 expression on ≥ 1% of immune cells. Kaplan-Meier method was utilised to analyse progression-free survival (PFS).
RESULTS: This exploratory biomarker analysis included 225 patients and tested HRD status [N = 190; positive, N = 125 (65.8%)], PD-L1 expression [N = 196; positive, N = 56 (28.6%)], and BRCA1/2 mutation status (N = 219). The HRD-positive patients displayed greater median PFS than the HRD-negative patients [17.9 months (95% CI: 14.5-22.1) versus 9.2 months (95% CI: 7.5-13.8)]. PD-L1 was predominantly expressed on immune cells. Positive PD-L1 expression on immune cells was associated with shortened median PFS in the patients with germline BRCA1/2 mutations [14.5 months (95% CI: 7.4-18.2) versus 22.2 months (95% CI: 18.3-NA)]. Conversely, positive PD-L1 expression on immune cells was associated with prolonged median PFS in the patients with wild-type BRCA1/2 [20.9 months (95% CI: 13.9-NA) versus 8.3 months (95% CI: 6.7-13.8)].
CONCLUSIONS: HRD remained an effective biomarker for enhanced olaparib efficacy in the Asian patients with PSROC. Positive PD-L1 expression was associated with decreased olaparib efficacy in the patients with germline BRCA1/2 mutations but associated with improved olaparib efficacy in the patients with wild-type BRCA1/2.
TRIAL REGISTRATION: NCT03534453. Registered at May 23, 2018.
METHODS: In this double-blind randomized clinical trial study, 50 NAFLD patients were divided into two groups of 25 participants who were treated with 520 mg/day of GSE or the placebo group for 2 months. The parameters of glycemic, lipid profile, blood pressure and steatohepatitis were measured before and after the intervention.
RESULTS: The GSE group had an average age of 43.52 ± 8.12 years with 15 women and 10 men, while the placebo group had an average age of 44.88 ± 10.14 years with 11 women and 14 men. After 2 months of intervention with GSE, it was observed that insulin, HOMA-IR, TC, TG, LDL-c, ALT, AST, AST/ALT, SBP, DBP and MAP decreased and QUICKi and HDL-c increased significantly (p-value for all
METHODS: Twenty women athletes with physical impairments who engaged in competitive Para sports in Saudi Arabia were interviewed. Interpretive phenomenological analysis was employed to extract themes elucidating the experiences of women athletes with physical impairments in Para sports.
RESULTS: Four dimensions were identified: (i) Exploring participation in sports; (ii) The positive impact of participation in sports; (iii) obstacles in participation in sport; and (iv) hopes and aspirations to improve participation in Para sports.
CONCLUSION: In Saudi Arabia, participation in Para sports functions as a powerful tool for empowering and socially integrating women with physical impairments. However, these women encounter challenges in accessing sports. Achieving empowerment in Para sports necessitates the establishment of an inclusive ecosystem that celebrates diversity and equality. Collaborative efforts from governments, sports organizations, communities, and individuals are indispensable in creating an environment where women with impairments can flourish in sports.
METHODS: Twenty-seven intact male goats (Ardi breed, 10 months of age, 27 kg liveweight) were divided into three treatment groups viz., the control (C) group, ear pulling (EP) group, and leg pulling (LP) group. Various behavioral, physiological, blood biochemical and hormonal responses were recorded before and after handling.
RESULTS AND DISCUSSION: The EP and LP goats had a higher frequency and intensity of vocalization as compared to control goats. The preslaughter handling stress intensities had a significant effect on the before and after handling values of heart rate, respiration rate, rectal temperature, and ear temperature. Further, among groups, the glucose value increased significantly upon preslaughter handling as compared to the baseline value. The LP goats had significantly higher after-handling value for lactate dehydrogenase (LDH) as compared to the before-handling value. The catecholamines (adrenaline and noradrenaline) and β-endorphin concentrations increased significantly upon preslaughter handling. The higher physiological, behavioral, blood biochemical, and hormonal response indicated higher preslaughter stress in EP and LP goats. Both levels of intensity revealed unfavorable responses in goats that may adversely affect animal welfare and meat quality. Thus, to ensure minimal adverse effects on behavior, physiology, blood enzymes, and hormonal responses, it is recommended to follow animal welfare principles when implementing preslaughter handling practices.
DESIGN: A cross-sectional design study.
METHODS: A convenience sampling method was used to enrol participants of childbearing age who visited two tertiary hospitals in Hang zhou, a city in eastern China, from June 2021 to March 2022. We conducted a face-to-face questionnaire survey with 520 participants and calculated the prevalence of intention-related factors. Multivariate logistic regression was used to analyse the independent influencing factors of fertility intention.
RESULTS: In total, 105 (20.2%) participants had the intention to have a third child. The results showed that 'employment status', 'age', 'reasons for wanting a third child', the considered 'biggest barrier to having a third child', 'views on the three-child policy', 'desired free services', 'supporting work policies' and 'assistance policies' were significant independent influencing factors of intention to have a third child (p-value
AIM: This review had three aims: first, to identify the outcome measures (OMs) reported in trials of dental behavior support; second, to categorize the component DBS techniques reported within interventions according to emerging agreed terminology; and, third, to map outcome measures to intervention type.
METHODS: A scoping review of trials evaluating DBS techniques was undertaken from 2012 to 2022. The review was prospectively registered. Studies were identified through Medline, Embase, and PsycINFO. Study abstracts were screened by two reviewers. Data were extracted by single selector. Outcome measures were sorted according to measurement domains (physiological, behavioral, psychological, and treatment). Responses were assimilated and summed to produce a refined list of distinguishable outcome measures. Intervention types were categorized according to accepted descriptors. Frequencies were presented; associations between outcome domain and DBS type were also reported (Chi-square test of independence).
RESULTS: A total of 344 trials were included in the review from an initial 14,793 titles / title and abstracts screened. Most involved children (n = 215), most were from India (n = 104), involving basic dental care (n = 117). The median number of outcome measures per trial was four (range = 1-12); 1,317 individual outcomes were reported, categorized as: psychological (n = 501, 38.0%); physiological (n = 491, 37.3%), behavioral (n = 123, 9.3%) or, treatment-related (n = 202, 15.3%). DBS interventions were split between 239 (45.7%) pharmacological and 283 (54.1%) non-pharmacological; 96.6% of interventions mapped to accepted descriptors. A significant relationship was noted between the type of intervention and the outcome domain reported.
CONCLUSION: The findings demonstrate massive variation in outcome measures of DBS interventions that likely lead to unnecessary heterogeneity, selective reporting, and questionable relevance in the literature. A large range of DBS interventions were mapped according to BeSiDe list. There is a need for consensus on a core outcome set across the spectrum of DBS techniques.
METHODS: A two-sample bidirectional MR analysis was conducted using data from individuals of European ancestry, utilizing genome-wide association studies (GWAS) statistics. The study selected instrumental single nucleotide polymorphisms (SNPs) significantly associated with circulating cytokines and applied multiple MR methods, including inverse variance weighted (IVW), Weighted Median, MR-Egger, Weighted Mode, Simple Mode, and MR-PRESSO. The traits analyzed were appendicular lean mass (ALM) and grip strength. Heterogeneity, robustness, and consistency of results were assessed using Cochran's Q statistic, MR-Egger regression, and "leave-one-out" sensitivity analyses.
RESULTS: The IVM-MR analysis showed a casual association between genetically predicted circulating levels of interleukin-16 and both ALM and grip strength (ALM: OR = 0.990, 95% CI: 0.980-1.000, p = .049; grip strength: OR = 0.971, 95% CI: 0.948-0.995, p = .020). Additionally, interferon-gamma-induced protein 10 (IP-10), interleukin-1-beta (IL-1β), and hepatocyte growth factor (HGF) were correlated with ALM and vascular endothelial growth factor (VEGF), interleukin-12 (IL-12), and interleukin-5 (IL-5) with grip strength. Comparable results were confirmed via the MR-Egger, Weighted Median, Weighted Mode, and Simple Mode methods. Sensitivity analysis showed no horizontal pleiotropy to bias the causal estimates.
CONCLUSION: The results suggest a significant causal effect of inflammatory cytokines on sarcopenia, offering new avenues for therapeutic target development. However, the study's focus on a European ancestry cohort limits its generalizability to other populations. Future research should aim to include diverse ethnic groups to validate and broaden these findings, thereby enhancing our understanding of sarcopenia's mechanisms in a global context.