Citations

Abstract Platinum-based chemotherapy remains a cornerstone of treatment for triple-negative breast cancer (TNBC), yet the molecular determinants governing platinum response remain poorly defined. By leveraging the randomized Phase II INFORM trial, which compared neoadjuvant cisplatin to anthracycline-based therapy in BRCA1/2 -mutant breast cancer—we identified miR-362-3p as a specific regulator of cisplatin sensitivity. Higher plasma miR-362-3p expression was exclusively associated with favorable clinical outcome in the cisplatin arm, with no association observed in the AC arm, decoupling platinum-specific vulnerability from general chemotherapy response. We used gain- and loss-of-function TNBC models to establish that miR-362-3p functions as a potent sensitizer to cisplatin in vitro and in vivo . Integrated TCGA analysis and experimental validation identified BCLAF1, a key regulator of DNA damage response, as a direct repression target of miR-362-3p. We uncovered a novel role for the miR-362-3p/ BCLAF1 axis in overcoming platinum resistance in TNBC.

Abstract Introduction and Objective This study aims to evaluate the learning curve and perioperative outcomes of single‐port extraperitoneal robotic radical prostatectomy (SP‐EP‐RARP) performed by a single surgeon at a high‐volume academic institution. Methods A retrospective review of a prospectively maintained database was conducted for patients who underwent SP‐EP‐RARP from September 2023 to August 2025. Key metrics included operative time, estimated blood loss, conversion rate, nerve‐sparing status, pathological margin status and continence (0–1 pad for safety), and 30‐day complication rate. Descriptive statistics were used, and outcomes were analysed chronologically to assess for trends suggesting a learning curve. Results The cohort included 53 patients who underwent extraperitoneal SP‐EP‐RARP. Median operative time was 213 min (IQR: 145–281). Median estimated blood loss was 100 mL (IQR: 75–125). Nerve‐sparing was attempted in 75.5% of cases. No assist or plus one ports were utilized. Final pathology revealed pT2 disease in 64.1% (34 cases), pT3a in 32.1% (17 cases) and pT3b in 3.7% (2 cases). Overall positive margin rate was 26.4%. Thirty‐day Clavien–Dindo Grades I–II complication rates were 11.3%, and no major complications or 90‐day complications were reported. Continence rates at 6 weeks, 3 months and 6 months were 72%, 72% and 75%, respectively. Stabilization of operative times and intraoperative outcomes occurred after approximately 25–30 cases. Conclusion SP‐EP‐RARP can be safely implemented by a newly graduated fellowship‐trained robotic surgeon with acceptable oncologic and functional outcomes. Initial learning can be estimated at approximately 25–30 cases.

Background Suicidal behaviour shows notable sex differences, and understanding whether genetic factors contribute to these differences is critical for identifying at-risk individuals and prevention. Objective We aim to investigate the genetic contribution to suicide attempts and examine whether genetics account for sex differences in incidence. Methods This population-based cohort study includes 3.1 million individuals born 1963–1998 and followed through Swedish National Registers, including hospitals and specialist outpatient diagnoses and cause of death data. Suicide attempts were identified using ICD codes, indicating intentional self-harm, self-harm using lethal methods or leading to hospitalisation, or resulting in death. Familial aggregation, coaggregation, pedigree heritability and genetic correlations were estimated using genealogical data. For sex-specific analyses, we examined mother–daughter, female sibling, father–son and male sibling pairs, separately. Findings Suicide attempts were more common among females than males (3.3% vs 2.6%). In both sexes, risk aggregated within families (ORs ranged 1.6–3.4 across relative types) and was higher in first-degree than second-degree relatives. Familial aggregation was stronger in females than in males, and in same-sex first degree relatives compared with cross-sex pairs. Pedigree heritability was 41.9% (95% CI 36.0 to 48.4%) and did not differ significantly by sex (female 51.4% (95% CI 40.1% to 58.6%), male 45.1% (95% CI 32.3% to 52.5%), Bootstrap p value 0.40). Suicide attempt showed moderate to high pedigree genetic correlations with psychiatric disorders, strongest with substance use disorders (SUD, r g =0.85 (95% CI 0.83 to 0.96)), with no significant sex differences. The genetic correlation between female and male suicide attempts was high (0.85 (95% CI 0.80 to 0.99)), suggesting a substantial genetic overlap. Conclusions Suicide attempt has a moderate heritable component that largely overlaps between females and males and with other psychiatric disorders, particularly SUD. Stronger familial aggregation in females and in same-sex pairs highlights the potential role of sex-specific environmental or social factors. Future research should focus on non-genetic contributors and their potential interaction with genetic factors to better understand and address sex disparities in suicidal behaviour Clinical implications Genetic risk for suicide attempt is substantial but does not fully explain sex differences in incidence. Clinicians should, therefore, consider non-genetic, including sex-specific environmental and social factors, alongside family history and psychiatric comorbidity when assessing suicidal risk.

Abstract Background Abdominal arterial calcification is a well-established predictor of cardiovascular events and mortality in kidney failure. Autosomal dominant polycystic kidney disease (ADPKD), a common genetic cause of kidney failure, presents with a distinct vascular profile. However, the burden of abdominal arterial calcification in ADPKD remains inadequately characterized. Clarifying these differences may improve cardiovascular risk stratification and transplant timing. Methods We conducted a retrospective cohort study of 4088 adult patients listed for kidney transplant at three Mayo Clinic sites (2005–2024). Patients were categorized by kidney failure cause: ADPKD vs. non-ADPKD. Abdominal arterial calcification was quantified on non-contrast computed tomography (CT) scans using a modified Agatston scoring method. Propensity score matching (1:1) adjusted for age, sex, race, lipid levels, left ventricular ejection fraction, dialysis exposure, coronary artery disease, neurovascular disease, and smoking history, was performed. Abdominal arterial calcification scores were compared between matched groups, and subgroup analyses evaluated abdominal arterial calcification severity across dialysis durations in ADPKD patients. Results After matching, 309 patients with ADPKD were compared with 309 non-ADPKD chronic kidney disease (CKD) controls. Abdominal arterial calcification scores were significantly lower in the ADPKD group (median: 425.3; IQR: 0.0–2033.5) than in the non-ADPKD group (median: 1256.8; IQR: 96.5–5033.8). Among ADPKD patients, abdominal arterial calcification scores increased with dialysis duration (P < .001). Conclusion ADPKD patients exhibit lower abdominal arterial calcification scores than their non-ADPKD counterparts after adjusting for clinical variables. Abdominal arterial calcification progression with dialysis highlights the importance of early transplant evaluation. This study introduces a novel adaptation of coronary calcium scoring software for quantifying abdominal calcification, offering a standardized approach to vascular risk assessment in kidney transplant candidates.

SUMMARY Goal: The purpose of this study was to enhance access to medication assistance programs (MAPs), which are crucial for providing free medications to patients who cannot afford them. These programs are particularly beneficial for the management of chronic conditions such as diabetes, heart failure, and cancer, for which medication adherence is vital for positive patient outcomes, and cost is a common barrier. Methods: This quality improvement project aimed at optimizing the MAP enrollment process. Interventions included the development of frequently asked questions documents, standardized templates for documentation, establishment of MAP technician office spaces, and standardization of patient referrals. A Mann-Whitney U test and a chi-square test were used to summarize the data in this study. Principal Findings: The project resulted in a 56% increase in new patient enrollments ( p < .01) and a 33% increase in medications provided, with a significant reduction in the average time from patient referral to application approval. Practical Applications: The project improved patient access to MAPs, optimized pharmacy technician resources, and significantly reduced processing times, an important factor in preventing treatment delays and improving patient care. Future plans include expanding the new enrollment process to annual reenrollments, formally establishing the MAP technician within departments, and considering additional pharmacy technician support in response to increasing demand for MAPs.

Lipid-based delivery systems (LDS), including lipid nanoparticles (LNPs) and liposomes, have become indispensable tools in modern biomedicine owing to their biocompatibility, capacity to encapsulate diverse therapeutic agents, and potential for targeted delivery. Despite their clinical success, conventional batch-based manufacturing methods are hindered by variability, limited scalability, and complex processing steps, slowing their broader translation. Microfluidic technologies offer a transformative solution by enabling precise fluid handling, rapid mixing, and reproducible production of LDS with tunable physicochemical attributes such as particle size, lamellarity, and drug-loading efficiency. This review highlights advances in microfluidic design strategies, including hydrodynamic flow focusing, staggered herringbone mixers, and toroidal micromixers, and evaluates how critical parameters such as flow rate, solvent composition, and lipid concentration influence LDS performance. Furthermore, we discuss the application of microfluidics in drug delivery, nucleic acid therapeutics, and vaccine platforms, underscoring its role in improving scalability, quality control, and clinical translation. Finally, we examine current challenges, including throughput limitations and solvent handling, while outlining future directions for integrating emerging materials and additive manufacturing to optimize LDS fabrication. Collectively, microfluidic platforms provide a promising pathway for next-generation lipid nanomedicines with enhanced precision, reproducibility, and therapeutic efficacy.

Moderate hyperoxia (30%–60% O 2 ) in premature infants promotes bronchial airway hyperresponsiveness (AHR) via airway smooth muscle (ASM), a key regulator of bronchoconstriction, bronchodilation, and remodeling. Understanding how O 2 exposure drives long-term bronchial changes in prematurity is critical for developing therapies for airway disease across the lifespan. Premature lungs have immature antioxidant defenses, potentially due to disrupted mitochondrial dynamics, increasing susceptibility to O 2 -induced oxidative stress. Thus, mitochondrial homeostasis is highly relevant to ASM dysfunction and airway disease. We propose that hyperoxia in prematurity promotes mitochondrial dysfunction, and that the gasotransmitter hydrogen sulfide (H 2 S) mitigates O 2 -induced mitochondrial damage in developing ASM. Human fetal ASM (fASM) cells were exposed to moderate hyperoxia to investigate the effects of exogenous H 2 S donors (GYY4137, AP39) and stabilization of cystathionine β-synthase (CBS), an H 2 S biosynthetic enzyme, on mitochondrial structure and function. Hyperoxia impaired fASM cell mitochondrial integrity, while H 2 S donors in particular, or CBS stabilization attenuated adverse O 2 effects on mitochondrial morphology, ROS, respiration, calcium regulation, and contractility. These findings highlight the therapeutic potential of H 2 S in the premature lung exposed to moderate hyperoxia.