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Magnetic force is used to drive ferromagnetic objects by shortening the magnetic flux path to reduce magnetic reluctance and increase magnetic conductivity. Based on this characteristic, magnetic force drives have been widely applied in various fields, such as military, transportation, and engineering, attracting significant attention. This paper proposes a method for the nonchain transport of steel shell ammunition based on magnetic force. The force generated by the minimal magnetic resistance in the air gap is utilized to drive the steel shell ammunition. A calculation model for the driving component is proposed using the Maxwell stress tensor method, and the accuracy of the model is verified by simulating ammunition motion curves using finite element software. Finally, prototype experiments are conducted to explore the motion conditions under uncertain ammunition masses. The magnetic nonchain ammunition transport mechanism features a simpler structure and lower maintenance costs, making it more suitable for use on unmanned platforms.

Up to 30% of patients with metastatic castration-resistant prostate cancer have deleterious mutations in genes involved in homologous recombination repair of DNA damage. The use of the PARP inhibitor olaparib in such patients was associated with longer progression-free survival and a longer time to pain progression than control therapy.

The immune cell landscapes in metabolic dysfunction-associated fatty liver disease (MAFLD) and their clinical relevance have not been explored. We used Ecotyper to identify immune cell states based on gene expression and examined their roles in metabolic dysfunction–associated steatotic liver disease (MASLD) progression. Limma was applied to identify differentially expressed genes (DEGs). Weighted gene co-expression network analysis (WGCNA) was used for module identification. Bidirectional Mendelian randomization (MR) analysis was used to validate the causal effect of AEBP1 on metabolic dysfunction-associated steatohepatitis (MASH). Out of 71 immune cell states, 32 showed significant differences between MASLD and MASH. The six most significant states were Fibroblasts.3 (tumor-associated), Epithelial.cells.3 (pro-angiogenic), PMNs.3 (classically activated), Macrophages.6 (M2 foam cell-like), Mast.cells.5, and Fibroblasts.7. All six cell states belong to the CE1 ecotype. Further analysis revealed that Fibroblasts.3 had the highest discriminatory ability in distinguishing MASH from MASLD, followed by Epithelial.cells.3 and Macrophages.6. At the ecotype level, CE1 showed the strongest ability to differentiate between MASLD and MASH, with a performance score (AUC) of 0.891. CE3 followed with a slightly lower performance (AUC = 0.826). Conversely, higher CE4 effectively differentiated MASLD from MASH (AUC = 0.871). Genes up-regulated in CE1-high samples were enriched in extracellular matrix (ECM) organization and the PI3K-Akt signaling pathway, while down-regulated genes were linked to copper ion responses. These genes formed three modules associated with fibroblasts and macrophages. We identified resveratrol, a polyphenolic compound, as a potential therapeutic drug capable of modulating these immune cell states. Protein-ligand docking analysis illuminated interactions between resveratrol and the Macrophages.6 marker gene AEBP1. This study provides a comprehensive exploration of the clinical significance of immune cell states in MAFLD. It identifies potential molecular mechanisms and therapeutic candidates. Further clinical trials are needed to validate the efficacy of resveratrol and explore its structure-activity relationships to develop targeted treatments.

Results of this double-blind, phase 2 trial showed patients with metastatic castration-resistant prostate cancer given olaparib plus abiraterone versus placebo plus abiraterone had significantly improved progression-free survival. Here, we present an exploratory analysis of pain and health-related quality of life (HRQOL). This double-blind, randomised, placebo-controlled, phase 2 trial was conducted across 41 urological oncology sites in 11 countries in Europe and North America. Eligible patients were aged 18 years or older, had metastatic castration-resistant prostate cancer, and had previously received docetaxel and up to one additional line of previous chemotherapy. Metastatic castration-resistant prostate cancer was defined as increasing prostate-specific antigen (PSA) concentration or other signs of disease progression despite androgen-deprivation therapy and serum testosterone concentrations at castrate levels (≤50 ng/dL), and with at least one metastatic lesion on bone scan, CT, or MRI. Eligible patients were randomly assigned (1:1) to receive oral olaparib (300 mg twice per day) plus oral abiraterone (1000 mg once a day) and oral prednisone or prednisolone (5 mg twice a day) or placebo plus abiraterone (1000 mg once a day) and prednisone or prednisolone (5 mg twice a day). Randomisation was done without stratification and by use of an interactive voice or web response system. A randomised treatment kit ID number was assigned sequentially to each patient as they became eligible. The primary endpoint (radiographic progression-free survival) has previously been reported. HRQOL was a prespecified exploratory patient-reported outcome. Patients were asked to complete the Brief Pain Inventory-Short Form (BPI-SF), single-item worst bone pain, Functional Assessment of Cancer Therapy-Prostate (FACT-P) questionnaire, and EuroQol-5 five-dimension five level (EQ-5D-5L) assessment at baseline, at weeks 4, 8, and 12, then every 12 weeks until treatment discontinuation. Prespecified outcomes were change from baseline in BPI-SF worst pain, single-item worst bone pain and FACT-P Total Outcome Index (TOI) scale scores, time to deterioration in BPI-SF worst pain and worst bone pain, and assessment of the EQ-5D-5L pain and discomfort domain. All analyses were exploratory and done in the full analysis set (all randomly assigned patients, including patients who were randomly assigned but did not subsequently go on to receive study treatment), with the exception of mean baseline and total change from baseline analyses, for which we used the population who had a valid baseline and at least one post-baseline assessment. This trial is registered with Clinicaltrials.gov, NCT01972217, and is no longer recruiting patients. Between Nov 25, 2014, and July 14, 2015, 171 patients were assessed for eligibility. 29 patients were excluded, and 142 were enrolled and randomly assigned to receive olaparib and abiraterone (n=71) or placebo and abiraterone (n=71). Data cutoff was Sept 22, 2017. Median follow-up was 15·9 months (IQR 8·1–25·5) in the olaparib plus abiraterone group and 24·5 months (8·1–27·6) in the placebo plus abiraterone group. Questionnaire compliance was generally high (43–100%). Least-squares mean changes from baseline in BPI-SF worst pain, single-item worst bone pain, and FACT-P TOI remained stable across all visits for patients in both treatment groups. Adjusted mean change in FACT-P TOI from baseline across all visits was −0·10 (95% CI −2·50 to 2·71) in the olaparib plus abiraterone group and −1·20 (−4·15 to 1·74) in the placebo plus abiraterone group (difference 1·30, 95% CI −2·70 to 5·30; p=0·52). Time to deterioration in pain was similar in both groups (BPI-SF worst pain HR 0·90 [95% CI 0·62–1·32], p=0·30; worst bone pain HR 0·85 [0·59–1·22], p=0·18). Improvement rates in the pain and discomfort domain of the EQ-5D-5L were similar in both groups from baseline to week 48, beyond which a higher proportion of patients in the olaparib plus abiraterone arm reported an improvement compared to the placebo plus abiraterone group. In these prespecified exploratory analyses, there was no significant difference in pain or HRQOL when olaparib was added to abiraterone. In this phase 2 trial, a statistically significant radiographic progression-free survival benefit was observed with the olaparib plus abiraterone combination. These results suggest that the improved survival benefits observed when combining olaparib with abiraterone does not result in different HRQOL compared with placebo plus abiraterone. Phase 3 studies are required to validate these results. AstraZeneca and Merck Sharp & Dohme, a subsidiary of Merck & Co, Rahway, NJ, USA.

The PROfound study showed significantly improved radiographical progression-free survival and overall survival in men with metastatic castration-resistant prostate cancer with alterations in homologous recombination repair genes and disease progression on a previous next-generation hormonal drug who received olaparib then those who received control. We aimed to assess pain and patient-centric health-related quality of life (HRQOL) measures in patients in the trial. In this open-label, randomised, phase 3 study, patients (aged ≥18 years) with metastatic castration-resistant prostate cancer and gene alterations to one of 15 genes (BRCA1, BRCA2, or ATM [cohort A] and BRIP1, BARD1, CDK12, CHEK1, CHEK2, FANCL, PALB2, PPP2R2A, RAD51B, RAD51C, RAD51D, and RAD54L [cohort B]) and disease progression after a previous next-generation hormonal drug were randomly assigned (2:1) to receive olaparib tablets (300 mg orally twice daily) or a control drug (enzalutamide tablets [160 mg orally once daily] or abiraterone tablets [1000 mg orally once daily] plus prednisone tablets [5 mg orally twice daily]), stratified by previous taxane use and measurable disease. The primary endpoint (radiographical progression-free survival in cohort A) has been previously reported. The prespecified secondary endpoints reported here are on pain, HRQOL, symptomatic skeletal-related events, and time to first opiate use for cancer-related pain in cohort A. Pain was assessed with the Brief Pain Inventory-Short Form, and HRQOL was assessed with the Functional Assessment of Cancer Therapy-Prostate (FACT-P). All endpoints were analysed in patients in cohort A by modified intention-to-treat. The study is registered with ClinicalTrials.gov, NCT02987543. Between Feb 6, 2017, and June 4, 2019, 245 patients were enrolled in cohort A and received study treatment (162 [66%] in the olaparib group and 83 [34%] in the control group). Median duration of follow-up at data cutoff in all patients was 6·2 months (IQR 2·2–10·4) for the olaparib group and 3·5 months (1·7–4·9) for the control group. In cohort A, median time to pain progression was significantly longer with olaparib than with control (median not reached [95% CI not reached–not reached] with olaparib vs 9·92 months [5·39–not reached] with control; HR 0·44 [95% CI 0·22–0·91]; p=0·019). Pain interference scores were also better in the olaparib group (difference in overall adjusted mean change from baseline score −0·85 [95% CI −1·31 to −0·39]; pnominal=0·0004). Median time to progression of pain severity was not reached in either group (95% CI not reached–not reached for both groups; HR 0·56 [95% CI 0·25–1·34]; pnominal=0·17). In patients who had not used opiates at baseline (113 in the olaparib group, 58 in the control group), median time to first opiate use for cancer-related pain was 18·0 months (95% CI 12·8–not reached) in the olaparib group versus 7·5 months (3·2–not reached) in the control group (HR 0·61; 95% CI 0·38–0·99; pnominal=0·044). The proportion of patients with clinically meaningful improvement in FACT-P total score during treatment was higher for the olaparib group than the control group: 15 (10%) of 152 evaluable patients had a response in the olaparib group compared with one (1%) of evaluable 77 patients in the control group (odds ratio 8·32 [95% CI 1·64–151·84]; pnominal=0·0065). Median time to first symptomatic skeletal-related event was not reached for either treatment group (olaparib group 95% CI not reached–not reached; control group 7·8–not reached; HR 0·37 [95% CI 0·20–0·70]; pnominal=0·0013). Olaparib was associated with reduced pain burden and better-preserved HRQOL compared with the two control drugs in men with metastatic castration-resistant prostate cancer and homologous recombination repair gene alterations who had disease progression after a previous next-generation hormonal drug. Our findings support the clinical benefit of improved radiographical progression-free survival and overall survival identified in PROfound. AstraZeneca and Merck Sharp & Dohme.

Background High-quality fertility care should be effective and safe but also patient-centered. We analyzed the difference in the patient-centered medical experiences between public and private fertility care in China, aiming to provide data support and a decision-making basis for optimizing the allocation of reproductive health care resources, and improving patient experience and compliance. Methods In this study, a multicenter cross sectional study was distributed among 1900 infertile Chinese patients at 10 reproductive medicine centres from July 2021 to April 2022. Patients’ experiences of infertility patients were analyzed. Univariate analysis and multivariate regression model analysis were used to analysis the factors influencing the differences in patients’ medical experiences between public and private fertility care. Results The questionnaire was completed by 1694 infertile couples (response rate of 89.16%) from 10 centres. Of the eight subscales, ‘care organization’ received the best ratings, and ‘information’ received the worst ratings. The total score of private fertility care was significantly higher than that of public fertility care. The subscale scores for ‘accessibility’, ‘information’ and ‘continuity and transition’ were significantly higher for private fertility care than for public fertility care. Further univariate and multivariate analyses found that the distance from the hospital, family income and pregnancy status were the main influencing factors of the patients’ medical experiences with public fertility care, while the stage of fertility treatment, infertility duration and pregnancy status were the main influencing factors of the patients’ medical experiences with private fertility care. Conclusions The subscale of patient-centered medical experiences for ‘accessibility’, ‘information’ and ‘continuity and transition’ were significantly higher for private fertility care than for public fertility care.

This study sought to examine the impact of Wnt7a/β-catenin signaling on depressive-like behaviors by using a rodent model subjected to chronic unpredictable mild stress (CUMS). Hippocampal Wnt7a and β-catenin expression levels were analyzed to investigate their mechanistic involvement in depression. Therefore, 20 male Sprague-Dawley rats were randomly allocated to the control or the CUMS experimental groups. The CUMS group underwent a 30-day stress protocol involving randomized stimuli. This study was authorized by the Ethics Committee (approval no. YXLL2022006). Following model establishment, depression-related behavioral phenotypes were quantitatively evaluated using standardized behavioral paradigms, the sucrose preference test (SPT), and the open field test (OFT), targeting core symptom domains such as anhedonia and alterations in locomotor activity. The morphology of hippocampal CA2 and DG area neurons was examined using hematoxylin and eosin staining, while immunofluorescence and Western blotting assessed Wnt7a and β-catenin expression. Western blotting also assessed GSK-3β and p-GSK-3β expression. Results indicated that CUMS rats showed markedly lower SPT indices ( P  < 0.05) and decreased OFT parameters (total distance traveled, central zone activity, speed, and central zone duration) versus controls ( P  < 0.05). Notably, Wnt7a, β-catenin, GSK-3β, and p-GSK-3β were significantly upregulated in the hippocampal tissues of rats in CUMS group ( P  < 0.05). Collectively, this study found that CUMS-induced depression is associated with a significant upregulation of hippocampal Wnt7a, β-catenin, and GSK-3β, along with increased GSK-3β phosphorylation. This correlative evidence points to Wnt pathway activation in depression pathogenesis and warrants further mechanistic investigation.

Thalassemia, a hereditary hemoglobinopathy characterized by impaired hemoglobin production, results in the premature destruction of erythrocytes and consequent anemia. However, the distinct hematological parameters and phenotypic expressions associated with different α-thalassemia genotypes in the pediatric population remain inadequately characterized. Therefore, this study was designed to perform a comparative analysis of clinical parameters between pediatric patients with α-thalassemia and healthy controls, to elucidate genotype-specific disease manifestations, and to inform optimized management strategies. This retrospective cross-sectional study enrolled 160 children with genetically confirmed α-thalassemia and 105 healthy controls in Hainan. Participants were categorized into silent carrier, mild, Hb H disease, and control groups. Comprehensive assessments included hematological parameters, biochemical profiles, coagulation function, growth -scores, and serum ferritin. Group comparisons were performed across genotypes and age strata (1-5, 6-11, 12-18 years) using appropriate statistical methods. Children diagnosed with Hb H disease exhibited the most severe hematological impairments, including growth retardation, elevated bilirubin levels, increased ferritin concentrations, and altered coagulation parameters. Among the genotypes studied, non-deletional types (-- /α α, -- /α α) demonstrated the most pronounced deficits. Growth -scores, encompassing weight-for-age (WAZ), height-for-age (HAZ), and body mass index-for-age (BAZ), were significantly reduced in the Hb H disease cohort, with deterioration observed as age increased. Notably, even silent carriers of the disease exhibited developmental delays during later childhood. Furthermore, iron overload and subclinical organ involvement were evident in older children affected by Hb H disease. The clinical phenotype of pediatric α-thalassemia is significantly influenced by both genotype and age, with non-deletional Hb H disease presenting the highest risk for systemic complications. These findings emphasize the necessity for genotype-specific monitoring, early nutritional and iron-chelation interventions, and a multidisciplinary follow-up approach to enhance long-term outcomes.

Background: Phase III randomized trial data have confirmed the activity for olaparib in homologous recombination repair (HRR) mutated metastatic castration-resistant prostate cancer (mCRPC) post next-generation hormonal agent (NHA) progression. Preclinical data have suggested the potential for a combined effect between olaparib and NHAs irrespective of whether an HRR gene alteration was present. NCT01972217 was a randomised double-blind Phase II study which evaluated olaparib and abiraterone versus placebo and abiraterone in mCRPC patients who had received prior chemotherapy containing docetaxel. The study showed that radiologic progression was significantly delayed by the combination of olaparib and abiraterone regardless of homologous recombination repair mutation (HRRm) status. The study utilized tumour, blood (germline), and circulating tumour DNA (ctDNA) analysis to profile patient HRRm status, but tumour tissue provision was not mandated, leading to relatively low tissue acquisition and DNA sequencing success rates not representative of real-world testing. Patients and methods: Further analysis of germline and ctDNA samples has been performed for the trial to characterize HRRm status more fully and robustly analyse patient response to treatment. Results: Germline and plasma testing increased the HRRm characterized population from 27% to 68% of 142 randomized patients. Tumour-derived variants were detectable with high confidence in 78% of patients with a baseline plasma sample (71% of randomized patients). There was high concordance across methodologies (plasma vs. tumour; plasma vs. germline). The HR for the exploratory analysis of radiographic progression-free survival was 0.54 (95% CI: 0.32–0.93) in favour of olaparib and abiraterone in the updated HRR wild type (HRRwt) group (n = 73) and 0.62 (95% CI: 0.23–1.65) in the HRRm group (n = 23). Conclusion: Our results confirm the value of plasma testing for HRRm status when there is insufficient high-quality tissue for multi-gene molecular testing. We show that patients with mCRPC benefit from the combination of olaparib and abiraterone treatment regardless of HRRm status. The combination is currently being further investigated in the Phase III PROpel trial.