Citations

Purpose This study investigates medical students’ opinions on the optimal timing for taking the emergency medicine (EM) clerkship and its effects on preparedness for subsequent clerkships and the USMLE (United States Medical Licensing Examination) Step 2 examination. Methods A cross-sectional survey was conducted among third- and fourth-year students at the Mayo Clinic Alix School of Medicine. The survey collected opinions on the optimal timing for the EM clerkship and its impact on self-efficacy as well as perceived preparedness for future clerkships and the USMLE Step 2 examination. Results Only 5% of third-year EM clerkship students felt they would have been more prepared in their fourth year. Conversely, 70% of fourth-year students believed they were more prepared than if they had taken it in their third year. Students were evenly split on if an earlier EM clerkship would have been helpful for subsequent clerkships. 88% of pre-USMLE Step 2 students found it helpful for Step 2, while 37% of post-USMLE Step 2 students felt it would have helped their preparedness. Additionally, 96% of students stated the EM clerkship increased their confidence in seeing patients. 43% of those who took the clerkship in their fourth year reported they would have considered EM as a specialty had they taken it earlier. Most students recommended taking the EM clerkship during the second 6 months of clerkships. Conclusion There are mixed opinions among medical students regarding the helpfulness of taking the EM clerkship earlier for subsequent clerkships and USMLE Step 2 preparedness. However, the majority recommend taking the EM clerkship earlier. A significant proportion of participants would have considered EM as a specialty if they had taken the clerkship earlier. Furthermore, 96% reported increased self-efficacy. Therefore, encouraging students to take the EM clerkship earlier may increase self-confidence and allow for earlier career exploration.

Abstract Objectives We aimed to assess the expression of biomarkers of response to antibody-drug conjugates (TROP2 and nectin-4) and immune microenvironment (NKG7, PD-L1, and B7-H3) in penile squamous cell carcinoma (pSCC). Methods Our archive was queried for patients who had a penectomy for pSCC between 2000 and 2022. Primary tumors were immunostained for B7-H3 and NKG7, while metastatic specimens were immunostained for TROP2 and nectin-4. Expression of PD-L1, TROP2, and nectin-4 in primary tumors was previously characterized. H-scores (0-300) were used to quantify expression. Associations between biomarkers, tumor-infiltrating lymphocytes (TILs), and clinicopathologic and outcome parameters were evaluated. Results For both TROP2 and nectin-4, H-scores within the lymph node metastases were higher compared to those within the primary tumors (mean, 264.5 vs 244.8, P = .0003; mean, 170.6 vs 146.7, P = .05, respectively; 33 paired specimens). For B7-H3 (n = 107), 32.7% of the primary tumors had an H-score of more than 0. In 34.8% of the cases, NKG7 expression was observed in 25% to 50% of the TILs. A significant association was noted between TIL density, B7-H3, NKG7, and PD-L1 expression. Conclusions Therapeutic strategies targeting TROP2 and nectin-4 hold promise for patients with advanced pSCC. The potential of PD-L1, B7-H3, and NKG7 for predicting response to immunomodulatory treatment warrants further research.

Background: In Kienböck disease with carpal collapse scaphocapitate fusion (SCF) and proximal row carpectomy (PRC), are mainstays of surgical treatment. This study analyzed objective and patient-reported outcomes after SCF or PRC in laborers versus nonlaborers. Methods: A retrospective cohort study of patients who underwent surgery for Kienböck disease within a single health system from 1976 to 2023 was conducted. Postoperative Disabilities of the Arm, Shoulder, and Hand (DASH) and Patient-Rated Wrist Evaluation (PRWE) scores were surveyed from the available population. Labor status, grip, ROM, and return to the operating room were collected and radiographs were analyzed. Results: Sixty-four patients underwent PRC, and 78 underwent SCF. Patients with PRC were significantly older than patients with SCF. Mean follow-up was 29 months (SD, 53 months). There was no significant difference in postoperative ROM or relative grip strength between the cohort groups. Laborers who underwent SCF demonstrated the least disability on DASH scores. There was no significant difference in postoperative DASH scores in PRC when comparing laborers versus nonlaborers. In contrast, the DASH and PRWE scores of patients who underwent SCF postoperatively varied between laborers and nonlaborers (mean ± SD, 11.1 ± 13.9 versus 30.5 ± 24.8, P = 0.005; and 17.5 ± 19.4 versus 42.3 ± 31.4, P = 0.024). Patients who underwent SCF had a greater rate of revision surgery compared with the PRC group (22 of 78 versus 6 of 64; P = 0.026). Wrist fusion rates were 19% for SCF compared with 1.6% for PRC ( P = 0.0007). Conclusions: SCF and PRC demonstrated no difference in postoperative ROM and grip based on labor status. Laborers with SCF had the least postoperative disability on DASH; however, SCF was associated with the need for additional surgical intervention and conversion to total wrist arthrodesis. CLINICAL QUESTION/LEVEL OF EVIDENCE: Therapeutc, III.

The growing global freshwater scarcity urgently requires innovative wastewater treatment technologies. This study hypothesized that biomimicry-inspired automated machine learning (AML) could effectively manage wastewater variability through adaptive processing techniques. Utilizing decentralized swarm intelligence, specifically the Respected Parametric Insecta Swarm (RPIS), the system demonstrated robust adaptability to fluctuating influent conditions, maintaining stable effluent quality without centralized control. Bio-inspired oscillatory control algorithms maintained stability under dynamic influent scenarios, while adaptive sensor feedback enhanced real-time responsiveness. Machine learning (ML) methods inspired by biological morphological evolution accurately classified influent characteristics (F1 score of 0.91), optimizing resource allocation dynamically. Significant reductions were observed, with chemical consumption decreasing by approximately 11% and additional energy usage declining by 14%. Furthermore, bio-inspired membranes with selective permeability substantially reduced fouling, maintaining minimal fouling for up to 30 days. Polynomial chaos expansions efficiently approximated complex nonlinear interactions, reducing computational overhead by approximately 35% through parallel processing. Decentralized swarm algorithms allowed the rapid recalibration of system parameters, achieving stable pathogen removal and maintaining effluent turbidity near 3.2 NTU (Nephelometric Turbidity Units), with total suspended solids consistently below 8 mg/L. Integrating biomimicry with AML thus significantly advances sustainable wastewater reclamation practices, offering quantifiable improvements critical for resource-efficient water management.

ABSTRACT Renal epithelial cell senescence and kidney aging have become the focus of scientific investigation. However, how epigenetic regulation in these processes remains elusive. Enhancer of zeste homolog 2 (EZH2), a histone methyltransferase, regulates trimethylation of histone H3 at lysine 27 (H3K27me3) and plays an important role in renal pathophysiology. In this study, we show that the expression of EZH2 is decreased in naturally aged and irradiation (IR)‐induced mouse kidneys, as well as in IR‐induced human renal cortical tubular epithelial (RCTE) cells through proteasome‐mediated degradation. Inhibition of EZH2 with its specific inhibitor 3‐DZNeP promotes tubular cell senescence and kidney aging characterized by an increase in the expression of senescence markers, including p16 and p21, in mouse kidneys and in IR‐induced RCTE cells. We show that EZH2 represses the transcription of p16 through trimethylation of H3K27me3, which directly binds to the promoter of p16. EZH2 represses the transcription of p21 through directly binding to the promoter of p21, and this process is involved in its interaction with p53 and its phosphorylation by ataxia‐telangiectasia mutated (ATM), a critical protein involved in the cellular response to DNA damage. Inhibition of ATM with its inhibitor decreased the phosphorylation of EZH2 and the binding of EZH2 to the promoter of p21 in IR‐treated RCTE cells in a p53‐dependent manner. This study suggests that EZH2 plays a critical role in preventing kidney aging and DNA‐damage‐induced renal tubular cellular senescence, in which senescence and kidney aging also result in the destabilization of EZH2, forming a negative feedback loop.

Abstract Background Percutaneous ablation of parathyroid adenomas provides a minimally invasive treatment option for primary hyperparathyroidism. However, the overall performance of this technique remains underexplored. This meta-analysis evaluates the effectiveness and safety of various ablation techniques for parathyroid adenomas. Methods Following Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines, multiple databases, including Ovid MEDLINE and Cochrane, were systematically searched. Studies that provided separate data for radiofrequency (RF), microwave ablation (MWA), and ethanol ablation technique were included. Outcomes of interest were changes in serum calcium, PTH, and phosphorus levels, along with normocalcemia rates at 6 to 12 months after ablation. Safety outcomes included transient hoarseness, permanent hoarseness, severe hemorrhage, major complications, and severe hypocalcemia. Data were pooled using a random-effects model, with pooled prevalence and 95% CIs calculated. Also, the publication bias was assessed with Egger's test for each outcome measure. Results Twenty studies (815 patients) were included. The posttreatment normocalcemia rate at 6 to 12 months was 85.6% (95% CI, 80.48-90.72). Serum PTH and calcium levels significantly decreased, with mean differences of 101.49 pg/mL (95% CI, 73.50-129.48) and 0.39 mmol/L (95% CI, 0.34-.45), respectively. Permanent hoarseness and major complications were rare, with incidences of 0.28% (95% CI, 0.00-1.05) and 0.31% (95% CI, 0.00-1.09). The safety and efficacy outcomes of RF, MWA, and ethanol ablation were comparable. Conclusion Our findings indicate that percutaneous ablation of parathyroid adenomas is safe and effective within the first year of the treatment. Additionally, they suggest that RF, MWA, and ethanol ablation techniques can each be employed depending on patients' needs without particular limitations.