Nevin Manimala

Eur Radiol. 2026 Apr 2. doi: 10.1007/s00330-026-12493-9. Online ahead of print.

ABSTRACT

OBJECTIVES: To evaluate the association between the cancer detectability by artificial intelligence (AI) and long-term survival outcomes in invasive breast cancer.

MATERIALS AND METHODS: This retrospective study analyzed consecutive women diagnosed with invasive breast cancer who underwent preoperative mammography between January and December 2013. Mammograms were analyzed using FDA-cleared AI software (Lunit INSIGHT MMG v1.1.8.2). Cancers were classified as AI-detected if correctly localized by AI, and AI-undetected if AI missed or mislocalized. Propensity score matching was performed using 29 clinical, pathological, and treatment-related covariates. Recurrence-free survival (RFS) and overall survival (OS) were compared using Kaplan-Meier estimates and Cox proportional hazards models.

RESULTS: Among 879 women (mean age ± standard deviation, 50.3 ± 10.2 years), AI correctly identified cancers in 83%. Before matching, the AI-detected group had higher recurrence (11% vs 5%; p = 0.02) and mortality rates (7% vs 1%; p = 0.003). Distant recurrence was also more prevalent in AI-detected cases (p = 0.04). After matching, no differences were observed in RFS (HR, 1.7 [95% CI: 0.8, 3.9]; p = 0.20) or OS (HR, 4.1 [95% CI: 0.5, 38.1]; p = 0.21). AI detectability was not associated with RFS (HR, 1.9 [95% CI: 0.9, 3.8]; p = 0.07) or OS (HR, 5.5 [95% CI: 0.8, 40.7]; p = 0.09) in multivariable analysis.

CONCLUSION: AI-detected breast cancers showed higher recurrence and mortality rates in the unadjusted analysis. However, after adjusting for confounders, AI detectability was not associated with RFS or OS, suggesting that AI may preferentially detect tumors with aggressive characteristics.

KEY POINTS: Question AI-based software for mammography interpretation is increasingly being integrated into practice, but the long-term prognostic implications of breast cancers detected or undetected by AI remain unclear. Findings In this retrospective study, AI detectability was not associated with recurrence-free (HR, 1.7; p = 0.20) or overall survival (HR, 4.1; p = 0.21) after propensity score matching. Clinical relevance AI may be more likely to detect biologically aggressive tumors, rather than directly influencing survival.

PMID:41927979 | DOI:10.1007/s00330-026-12493-9

Int J Obes (Lond). 2026 Apr 2. doi: 10.1038/s41366-026-02072-9. Online ahead of print.

ABSTRACT

PATHWEIGH is the first intervention scaled to 274,182 patients to mitigate population weight gain. In a stepped-wedge cluster-randomized pragmatic trial in Colorado, USA, 56 primary care clinics were randomly assigned to three clusters with staggered start dates for a one-way crossover from usual care to the intervention phase. The intervention (PATHWEIGH) included: health system primary care leadership endorsement, an electronic health record (EHR)-driven care process designed to prioritize, facilitate and expedite weight management, and implementation strategies to support use of the care process and educate clinicians on obesity treatment. The objective of the current analysis was to identify mediators and moderators associated with successful population-level weight management in primary care. The majority of subgroups (moderators) benefited from the intervention because they either lost more weight, gained less weight or switched from weight gain to weight loss compared to usual care. Patient and/or provider use of an EHR component of the intervention mediated 37% of additional patient weight loss and use of an anti-obesity medication mediated 4% over 18 months (p < 0.001 for all comparisons). Altogether, the intervention had favorable effects on patient weight across the subgroups, particularly when a patient or provider used ≥1 EHR component of PATHWEIGH.

PMID:41927969 | DOI:10.1038/s41366-026-02072-9

Commun Med (Lond). 2026 Apr 2. doi: 10.1038/s43856-026-01528-3. Online ahead of print.

ABSTRACT

BACKGROUND: Growing evidence implicates early metabolic dysfunctions in retinal ganglion cells (RGCs) as a contributor to both high- and normal-tension glaucoma, yet no approved therapy directly protects RGCs to preserve vision. We aimed at identifying a safe, druggable neuroprotective strategy that restores RGC metabolic homeostasis for glaucoma therapy.

METHODS: Using a live-cell mitochondrial screen in human embryonic stem cell-derived retinal ganglion cells (H7; female donor), we identified the clinically tested 5-HT1A antagonist WAY-100635 (WAY) as a neuroprotective agent. Mechanisms are probed by pharmacologic competition with agonist 8-OH-DPAT, cAMP assays, and PGC-1α dependent mitochondrial-biogenesis tests. RGC metabolism and survival are assessed by Seahorse and apoptosis assays. In vivo efficacy is evaluated in acute optic-nerve crush (ONC) and microbead-induced ocular-hypertension glaucoma models using histology, brain MRI, visual-acuity, contrast sensitivity testing, and flash VEPs to quantify cortical responses in wild-type C57BL/6 J male mice. Statistics used two-tailed Student’s t-tests or ANOVA, as appropriate.

RESULTS: Here we show that WAY elicits a reversible cAMP surge that drives PGC-1α dependent mitochondrial biogenesis and reduces apoptosis in hRGCs. In glaucoma-associated OPTN^E50K hRGCs, it restores mitochondrial fitness, attenuates excitotoxicity, and shifts metabolism toward aerobic glycolysis, while in progenitors, WAY enhances cristae maturation, oxidative phosphorylation, accelerating RGC specification. Systemic dosing in ONC mice preserves RGC somata, retinal function (PhNR), and optic-pathway integrity. WAY-treated glaucoma mice show preserved visual acuity and fVEP propagation to cortex, halting glaucoma progression.

CONCLUSIONS: A clinically tested 5-HT1A antagonist WAY restores RGC metabolic homeostasis and preserves visual-pathway function across acute and chronic injury models, without detected systemic toxicity, supporting development of a neuroprotective candidate for glaucoma and potentially for other mitochondrial optic neuropathies.

PMID:41927968 | DOI:10.1038/s43856-026-01528-3

Ann Surg Oncol. 2026 Apr 2. doi: 10.1245/s10434-026-19458-8. Online ahead of print.

ABSTRACT

BACKGROUND: This study aimed to compare the perioperative and oncologic outcomes between robotic and open retroperitoneal lymph node dissection in patients with testicular cancer.

METHODS: The study was conducted in accordance with the PRISMA guidelines, and quality assessment was performed following the AMSTAR criteria. A systematic search was performed in Embase, PubMed, and Web of Science databases, with the search period up to July 2025. Statistical analysis was performed using Stata 17 software.

RESULTS: The current results showed that compared with open retroperitoneal lymph node dissection (O-RLND), robotic retroperitoneal lymph node dissection (R-RPLND) had a shorter hospital length of stay (effect, – 3.68; 95 % confidence interval [CI], – 4.16 to – 3.21; P < 0.05), less estimated blood loss (effect, – 296.09; 95 % CI, – 416.62 to – 175.55; P < 0.05), and a lower overall complication rate (relative risk, 0.66; 95 % CI, 0.49-0.89; P < 0.05). Lymph node production and recurrence rate did not differ significantly between the two.

CONCLUSION: Robotic retroperitoneal lymph node dissection appears to be safer than O-RLND and has a faster postoperative recovery. Oncologic outcomes did not differ significantly, but more research is needed to explore further.

PMID:41927958 | DOI:10.1245/s10434-026-19458-8

AAPS J. 2026 Apr 3;28(3):85. doi: 10.1208/s12248-026-01213-2.

ABSTRACT

This study presents a workflow for virtual bioequivalence (VBE) assessment of 3-month paliperidone palmitate (PP) long-acting injectable (LAI) suspensions using a novel physiologically-based pharmacokinetic (PBPK) model. The mechanistic absorption and PBPK model was implemented in the Simcyp® Simulator and calibrated against individual concentration-time profiles derived from a published and validated population pharmacokinetic model. The model was able to accurately simulate drug concentration profiles after PP administration. Across 1000 subjects, four model-predicted bioequivalence (BE) metrics, including C_max,ss and AUC_tau,ss, differed by at most 10% from validation data. The initial mean drug particle radius was assessed as the critical formulation attribute in the VBE analysis. We conducted extensive VBE simulations to evaluate the required sample size of parallel trial designs for a given statistical power. The statistical power of two-one-sided t tests (TOST) to declare BE was estimated from the passing rate of Monte Carlo simulated VBE trials. Power calculations using the validated model indicated that a VBE trial with a minimum of 160 subjects per arm is required to achieve at least 80% power for declaring BE when the formulations are identical in terms of mean particle size. If the mean drug particle radius between test and reference formulations differs by 20%, the required sample size for BE demonstration approximately doubles to maintain the same power. This suggests that particle size affects formulation variability. The power calculations demonstrated that BE assessments were very sensitive to formulation differences in drug particle radius and to the parametrization of the model. These findings emphasize the critical need for rigorous model validation to ensure reliable VBE assessments.

PMID:41927954 | DOI:10.1208/s12248-026-01213-2

Sci Rep. 2026 Apr 2. doi: 10.1038/s41598-026-46698-1. Online ahead of print.

ABSTRACT

Necrotising enterocolitis (NEC) is a devastating gastrointestinal disease of premature infants, in which hypoxia-induced apoptosis plays a critical role in intestinal epithelial injury. The balance between pro-apoptotic and anti-apoptotic proteins, particularly Bax and Bcl-2, as well as the hypoxia-responsive transcription factor HIF-1α, are key determinant of epithelial survival. Sildenafil citrate, a phosphodiesterase-5 inhibitor, has been shown to improve microcirculation and exert anti-apoptotic effects through nitric oxide-cGMP signalling, but its role in NEC-related intestinal injury remains poorly understood. This study aimed to evaluate the protective effects of sildenafil on apoptosis in a hypoxia-ischemia-induced NEC-like intestinal injury model. A total of 75 Wistar rat pups were randomly assigned to six groups: control, NEC, vehicle (saline+DMSO), and sildenafil-treated groups (1, 5, and 10 mg/kg/day). Sildenafil was administered intraperitoneally for 4 days before NEC induction. NEC was induced by hypoxia (100% nitrogen for 60 s, twice daily for 48 h) and followed by cold stress (10 min at 4 °C). Intestinal tissues were collected for histopathological scoring, caspase-3 immunohistochemistry, and quantitative RT-PCR analysis of HIF-1α, Bax, and Bcl-2 expression. Data were analysed using ANOVA and Kruskal-Wallis tests, with p ≤ 0.05 considered statistically significant. Pups subjected to hypoxia-induced intestinal ischemia exhibited severe villous damage, elevated histological injury scores, and marked upregulation of HIF-1α and Bax, along with downregulation of Bcl-2. Caspase-3 immunoreactivity strongly correlated with histological injury (Spearman’s ρ = 0.795, p < 0.001). Sildenafil pretreatment reduced histological damage and apoptosis in a dose-dependent manner. The Sil_10 group showed the lowest injury score (1.06 ± 0.4, p < 0.0001 vs. NEC), significantly reduced Caspase-3 labelling, suppressed Bax and HIF-1α expression, and increased Bcl-2 levels, resulting in a markedly reduced Bax/Bcl-2 ratio compared with NEC (p < 0.0001). Sildenafil attenuates hypoxia-induced, ischemia-dominant NEC-like intestinal injury by modulating apoptotic and hypoxia-related pathways, lowering HIF-1α expression, reducing Bax/Bcl-2 ratio, and preserving epithelial integrity. These findings provide novel histological and molecular evidence for the anti-apoptotic effects of sildenafil in experimental NEC, highlighting HIF-1α modulation as a potential therapeutic strategy.

PMID:41927903 | DOI:10.1038/s41598-026-46698-1

Sci Rep. 2026 Apr 2. doi: 10.1038/s41598-026-47139-9. Online ahead of print.

NO ABSTRACT

PMID:41927879 | DOI:10.1038/s41598-026-47139-9

Sci Rep. 2026 Apr 2. doi: 10.1038/s41598-026-46957-1. Online ahead of print.

ABSTRACT

Since its nationwide implementation in 2014, China’s standardized residency training system has aimed for homogeneous clinical competency outcomes. In obstetrics and gynecology, where minimally invasive techniques now dominate, this goal faces significant challenges. The high volume of laparoscopic procedures necessitates efficient training, yet traditional apprenticeship models within real-world clinical settings are often inconsistent, time-intensive, and carry inherent patient safety concerns. These factors can hinder the systematic and equitable skill acquisition required for reliable, standardized proficiency across all trainees. This study aimed to evaluate the efficacy of a structured laparoscopic simulator curriculum in improving basic surgical skills and promoting skill-level convergence among obstetrics and gynecology residents at different training stages. A prospective educational intervention was conducted at a national residency training base. Thirty residents (PGY-1, n = 10; PGY-2, n = 10; PGY-3, n = 10) undertook a standardized four-week curriculum on a box-trainer, covering four core skill modules. Performance was assessed weekly by task completion time and analyzed using repeated-measures ANOVA. Significant improvements in task efficiency were observed among PGY-1 and PGY-2 residents over the training period (p < 0.05), whereas PGY-3 residents maintained stable, proficient performance. By the end of the curriculum, no statistically significant differences in performance were observed among the three groups at Week 4. A structured simulator-based curriculum can effectively enhance basic laparoscopic skills among residents and may help achieve comparable skill outcomes across different training levels, indicating its potential as a useful adjunct to traditional clinical training.

PMID:41927862 | DOI:10.1038/s41598-026-46957-1

Sci Rep. 2026 Apr 2. doi: 10.1038/s41598-026-45702-y. Online ahead of print.

ABSTRACT

This study aimed to assess male barbers’ knowledge, attitudes, and practices (KAP) in Herat City, Afghanistan, regarding HBV/HCV transmission and prevention. A cross-sectional survey using a structured, localized KAP questionnaire based on validated tools was conducted from April to June 2025, involving 283 practicing male barbers in Herat. Descriptive statistics summarized binary scores, while associations between KAP and sociodemographic factors were analyzed using chi-square or Fisher’s exact tests, and logistic regression has also been applied (p < 0.05). Among 283 male barbers, good knowledge was higher among those aged 31-50 years (73.7%) compared with those aged 21-30 years (58.5%) and 18-20 years (48.5%) (p = 0.008), and among those with > 8 years of work experience (70.5%) compared with those with ≤ 8 years (45.8%) (p < 0.001). Good preventive practice was higher among barbers who had formal training (68.8%) compared with those without training (48.0%) (p < 0.001). In multivariable analysis, barbers with > 8 years of work experience had higher odds of good knowledge than those with ≤ 8 years (AOR = 2.74; 95% CI 1.40-5.35) (p = 0.003). For attitude, barbers with fair economic status had lower odds of a positive attitude compared with those with good economic status (AOR = 0.25; 95% CI 0.06-0.97) (p = 0.046), while those working > 12 h per day had higher odds of a positive attitude than those working ≤ 12 h (AOR = 1.98; 95% CI 1.11-3.51) (p = 0.020). For practice, barbers aged 21-30 years had lower odds of good practice than those aged 18-20 years (AOR = 0.32; 95% CI 0.16-0.66) (p = 0.002), barbers serving > 5 customers/day had lower odds of good practice than those serving ≤ 5 customers/day (AOR = 0.50; 95% CI 0.29-0.88) (p = 0.016), and barbers without formal training had lower odds of good practice than those with training (AOR = 0.50; 95% CI 0.29-0.89) (p = 0.017). Male barbers in Herat City demonstrate commendable hygiene practices but exhibit significant gaps in their knowledge and attitudes regarding HBV/HCV. These findings highlight the need for targeted education and vaccination programs, integrated into barber training, to improve preventive attitudes and reduce the risk of viral transmission. Public health interventions that incorporate barbers into hepatitis control strategies are essential for mitigating the spread of HBV/HCV in the community.

PMID:41927830 | DOI:10.1038/s41598-026-45702-y

J Imaging Inform Med. 2026 Apr 2. doi: 10.1007/s10278-026-01934-y. Online ahead of print.

ABSTRACT

This study proposes a Residual Conditional Variational Autoencoder model (ResCVAE-Harmonizer) that integrates batch information and clinical covariates for multi-center feature harmonization and systematically and comprehensively evaluates its harmonization performance. This study collected 806 cases from 9 different centers. After preprocessing, three types of features were extracted from PET and CT images: low-dimensional radiomic features, high-dimensional radiomic features, and deep learning features based on 3D-DenseNet-121. Each feature type was harmonized using ComBat, CovBat, and the proposed ResCVAE-Harmonizer. Both harmonized and original features were included in a comprehensive evaluation framework comprising variance homogeneity analysis, multi-center classification test, and downstream task effectiveness evaluation. The ResCVAE-Harmonizer significantly improved cross-center feature consistency. Levene’s test results showed a general reduction in – log₁₀(p) values after harmonization, with more pronounced improvements observed in low- and high-dimensional radiomic features. In center classification tasks, ResCVAE-harmonized features demonstrated greater stability across four classifiers and outperformed the original features. For the downstream survival prediction task, PET deep learning features processed by ResCVAE achieved the highest C-index (0.8920, 95% CI 0.8514-0.9325), surpassing those of the original features (0.8765), ComBat (0.8909), and CovBat (0.8455). Similarly, the C-index for CT deep features improved to 0.8296 (95% CI 0.7715-0.8877). Kaplan-Meier survival stratification based on ResCVAE features showed clearer separation between high- and low-risk groups, with statistically significant log-rank test results. While slightly inferior to ComBat in linear variance consistency, ResCVAE-Harmonizer effectively eliminated both linear and nonlinear batch effects and significantly enhanced survival prediction performance, demonstrating strong research potential.

PMID:41927822 | DOI:10.1007/s10278-026-01934-y