Nevin Manimala

JAMA Surg. 2026 Jun 3. doi: 10.1001/jamasurg.2026.1796. Online ahead of print.

ABSTRACT

IMPORTANCE: Sleep timing regularity is increasingly recognized as a determinant of cognitive performance, yet its influence on surgeons’ well-being and patient safety remains unexplored.

OBJECTIVE: To evaluate the association between surgeons’ sleep timing regularity and major adverse events in their patients.

DESIGN, SETTING, AND PARTICIPANTS: This multicenter prospective cohort study was conducted from November 1, 2020, to December 31, 2021, across 14 surgical departments in 7 specialties at 4 university hospitals in France. Patients were excluded if they were younger than 18 years, underwent palliative surgery, had incomplete operative time stamps, or were operated on by surgeons with invalid sleep data. Study data were analyzed from January to June 2025.

EXPOSURES: Surgeons’ sleep was continuously monitored using actigraphy. Sleep timing regularity in the 30 days preceding surgery was quantified using midsleep time (midpoint between bedtime and get-up time). Social jet lag (SJL) was defined as the absolute difference between midsleep times on free days and workdays, and midsleep time variability was the SD of daily midsleep times.

MAIN OUTCOMES AND MEASURES: Outcomes included major adverse events within 30 days postoperatively, including inpatient death, prolonged intensive care unit stay, reoperation, or severe complications. Mixed-effects multivariable models were adjusted for surgeon sleep duration, midsleep time, age, sex, professional status, working hours, night shifts, patient case mix (ie, a composite risk score incorporating patient comorbidities and surgery characteristics), and time of incision, with a random effect for surgeons. Surgeon burnout was assessed using the Maslach Burnout Inventory.

RESULTS: Among 7117 operations (7117 patients; mean [SD] age, 55.9 [17.5] years; 3877 female [54.5%]) performed by 38 attending surgeons (mean [SD] age at study start, 46.1 [8.5] years; 30 male [79%]), 1410 (19.8%) resulted in a major adverse event. SJL of 2 or more hours (342 operations [4.8%]; 7 surgeons) was associated with increased risk of major adverse events compared with less than 1 hour (adjusted relative risk [RR], 1.36; 95% CI, 1.04-1.69) and 1 to 2 hours (RR, 1.45; 95% CI, 1.12-1.81). Midsleep time variability of 60 minutes or longer (864 operations [12.1%]; 20 surgeons) was not associated with adverse outcomes. Surgeons with burnout had higher median [IQR] social jet lag (75 [47-94] vs 52 [38-61] minutes; P = .04) and midsleep time variability (54 [44-68] vs 43 [36-48] minutes; P = .01) than those without burnout.

CONCLUSIONS AND RELEVANCE: Patients operated on by surgeons experiencing substantial social jet lag had a higher associated risk of major adverse events. Interventions promoting regular sleep timing and reducing circadian misalignment may improve surgeon burnout and patient safety.

PMID:42234451 | DOI:10.1001/jamasurg.2026.1796

JAMA Psychiatry. 2026 Jun 3. doi: 10.1001/jamapsychiatry.2026.1183. Online ahead of print.

ABSTRACT

IMPORTANCE: Childhood trauma is associated with increased risk for bipolar disorder, but the biological mechanisms of this association remain incompletely defined. Gray matter differences observed after trauma exposure overlap with those reported in bipolar disorder, suggesting that the association of childhood trauma with bipolar disorder might be mediated through brain morphology.

OBJECTIVE: To determine whether cortical thickness, cortical surface, or subcortical volume mediate the association of childhood trauma with bipolar disorder.

DESIGN, SETTING, AND PARTICIPANTS: This case-control study conducted a cross-sectional analysis of individuals with bipolar disorder and healthy controls from 19 international cohorts (Enhancing NeuroImaging Genetics Through Meta-Analyses [ENIGMA] Bipolar Disorder Working Group) from January 2010 to December 2022. Data were analyzed from January 2025 to January 2026.

EXPOSURES: The primary exposure was the severity of total childhood trauma assessed with the Childhood Trauma Questionnaire, with secondary analyses of 5 subscales (emotional neglect and abuse, physical neglect and abuse, and sexual abuse).

MAIN OUTCOMES AND MEASURES: The primary outcome was bipolar disorder diagnosis (case vs control). The primary measure was the mediation effects of childhood trauma on diagnosis via gray matter (75 bilateral-averaged cortical thickness, surface, and subcortical volume measures). The mediation pathway from severity of childhood trauma to bipolar disorder through brain morphology was specified a priori. High-dimensional mediation analysis, with leave-one-site-out cross-validation and permutation testing for significance (false discovery rate [FDR]), was conducted.

RESULTS: The final sample included 2221 healthy controls (mean [SD] age, 35.6 [13.2] years; 1274 female [57%]) and 1031 participants with bipolar disorder (mean [SD] age, 38.6 [13.7] years; 579 female [56%]). Severity of childhood trauma was directly associated with higher likelihood of having a bipolar disorder diagnosis (median coefficient, 0.841; 95% CI, 0.834-0.851; range, 0.776-0.893; FDR P < .001). Less than 1% of the association between childhood trauma and bipolar disorder was mediated by brain morphology. Statistically significant mediators were hippocampal volume (median coefficient, 0.004; 95% CI, 0.002-0.005; range, 0-0.008; FDR P < .001), medial orbitofrontal gray matter thickness (median coefficient, 0.002; 95% CI, 0.002-0.003; range, 0-0.004; FDR P < .001), and superior frontal gyrus gray matter thickness (median coefficient, 0.002; 95% CI, 0.002-0.003; range, 0-0.005; FDR P < .001).

CONCLUSIONS AND RELEVANCE: This study found that severity of childhood trauma exposure was associated with bipolar disorder diagnosis in part through a smaller hippocampus, thinner cortex in the medial orbitofrontal gyrus, and thinner cortex in the superior frontal gyrus. The identification of this mechanistic pathway improves understanding of the disorder, could help to identify those at risk, and enable the development of new interventions.

PMID:42234441 | DOI:10.1001/jamapsychiatry.2026.1183

Gen Thorac Cardiovasc Surg. 2026 Jun 3. doi: 10.1007/s11748-026-02328-1. Online ahead of print.

ABSTRACT

OBJECTIVES: The technical complexity of complex segmentectomy for non-small cell lung cancer raises concerns regarding perioperative safety and oncologic adequacy. We evaluated whether complex segmentectomy compromises perioperative or long-term outcomes compared with simple segmentectomy.

METHODS: We retrospectively reviewed 542 consecutive patients undergoing anatomical segmentectomy for resectable non-small cell lung cancer at a single cancer center (2014-2024). Simple segmentectomy was defined as upper division, lingular, S6, or basal segmentectomies; others were classified as complex segmentectomy. Perioperative, overall, and recurrence-free survival were compared between simple (n = 284) and complex (n = 258) segmentectomies. Cox proportional hazards models identified predictors of recurrence-free survival.

RESULTS: Baseline demographics and pulmonary function were similar between groups, whereas complex segmentectomy was more frequently performed for smaller ground-glass-dominant tumors using video-assisted thoracoscopic surgery. Operative time was slightly shorter for complex segmentectomy, while rates of major complications requiring intervention and 30-/90-day mortality were similar. At a median follow-up of 49 months, the 5-year overall survival and recurrence-free survival rates for the entire cohort were 91.5% and 85.2%, respectively, with no statistically significant differences between the complex segmentectomy and simple segmentectomy groups. In multivariable analysis, age, sex, and lymphovascular invasion were independent predictors of RFS, whereas smoking history, radiological tumor appearance, ND2 dissection, and complex segmentectomy were not.

CONCLUSIONS: In this single-center cohort, complex segmentectomy achieved perioperative and long-term outcomes comparable to those of simple segmentectomy and appears to be an oncologically acceptable, parenchyma-sparing option for appropriately selected patients with resectable non-small cell lung cancer.

PMID:42234389 | DOI:10.1007/s11748-026-02328-1

J Endocrinol Invest. 2026 Jun 3. doi: 10.1007/s40618-026-02937-w. Online ahead of print.

ABSTRACT

BACKGROUND: Current guidelines recommend screening for primary aldosteronism (PA) only in patients with hypertension and/or hypokalemia. However, recent evidence raises the question of whether normotensive patients with adrenal incidentalomas (AIs) might also exhibit biochemical features of aldosterone dysregulation. This study aimed to evaluate the prevalence and clinical significance of aldosterone-related abnormalities in normotensive patients with AIs.

METHODS: We retrospectively analyzed 452 patients with AIs, of whom 202 were normotensive. Hormonal evaluation included plasma aldosterone concentration (PAC) and either plasma renin activity or concentration. The aldosterone-to-renin ratio (ARR) was considered elevated if > 20 when calculated with plasma renin activity or > 1.8 when using direct renin concentration. We performed comparative analyses according to blood pressure (BP) status, PAC, ARR, and combined aldosterone phenotypes (PAC > 10 ng/dL with elevated ARR, PAC > 10 ng/dL with normal ARR, and PAC ≤ 10 ng/dL with elevated ARR). Median follow-up was 3 years.

RESULTS: Normotensive patients had a median age of 57 years (IQR 14), and 46.3% were male. Among them, 44.8% had PAC > 10 ng/dL and 33.3% had an elevated ARR. Serum potassium levels were within the normal range (median 4.3 mmol/L, IQR 0.5). In normotensive patients, no significant differences in systolic or diastolic BP were observed according to PAC or ARR alone. In the overall cohort, diastolic BP was higher in patients with elevated ARR. Importantly, diastolic BP differed significantly across combined aldosterone phenotypes (p = 0.015), with higher values observed in patients with PAC > 10 ng/dL and elevated ARR compared with those with PAC > 10 ng/dL and normal ARR (adjusted p = 0.048). During follow-up, incident hypertension was numerically higher among ARR-positive normotensive patients (18.4% vs. 11.0%), although this difference did not reach statistical significance (p = 0.215). A total of 10 patients were diagnosed with confirmed PA, including two normotensive individuals.

CONCLUSION: Biochemical evidence of aldosterone dysregulation is common in patients with AIs, including normotensive individuals. While isolated elevations in PAC or ARR were not associated with significant BP differences, the coexistence of elevated PAC and ARR identified a subgroup with a more pronounced hemodynamic profile. These findings support the concept of a continuum of aldosterone excess and suggest that combined biochemical phenotypes may be more informative than isolated markers. Further prospective studies are needed to clarify the clinical implications of these findings and to define optimal screening strategies in this population.

PMID:42234347 | DOI:10.1007/s40618-026-02937-w

Eur Phys J E Soft Matter. 2026 Jun 3;49(6):47. doi: 10.1140/epje/s10189-026-00577-9.

ABSTRACT

We investigate the influence of drop volume on partial wetting of sessile drops on a horizontal solid substrate for up to large Bond numbers, considering water on both polymethyl methacrylate (PMMA) and aluminum-coated substrates, as well as glycerol on PMMA. The horizontal orientation of the substrate, along with methods for creating sessile drops, facilitated the rotational symmetry of drops to perform controlled and reproducible experiments. In particular, we explore the manner in which the statistic macroscopic contact angle (MCA) depends on the sessile drop volume or related Bond numbers, whether the drop is injected via a syringe positioned above the substrate (DSA30 Krüss equipment) or from below the substrate through a tiny hole drilled in it. In both cases, experimental results exhibit that as the drop volume is increased spanning Bond numbers in the range [0.1-14], the contact line advances on the substrate and the MCA significantly decreases down to an asymptotic value.

PMID:42234346 | DOI:10.1140/epje/s10189-026-00577-9

Bull Math Biol. 2026 Jun 3;88(6):101. doi: 10.1007/s11538-026-01663-x.

ABSTRACT

This study develops a behavior-disease feedback model grounded in imitation dynamics to analyze optimal long-term epidemic coexistence strategies from both static and dynamic perspectives. Analytical findings reveal that the stability of the system depends on both the basic reproduction number and the behavioral threshold, with the latter and risk attention jointly determining optimal static intervention intensity. Data-driven analyses of influenza (Shanxi) and COVID-19 (Shanghai) show that adaptive public behavior can drive recurrent epidemic waves. In dynamic optimization simulations involving control of transmission rate alone or jointly with behavioral threshold, key insights include: seizing the critical rapid-growth window prevents both strategy oscillations and epidemic rebound resulting from delayed intervention; faster public response lowers both control costs and infection burden while accelerating attainment of control goals; stricter prevalence constraints require earlier and longer interventions, where proactive phased strategies outperform short, high-intensity measures in cost-effectiveness; achieving lower target prevalence necessitates earlier action and greater public caution, advancing the infection peak but substantially reducing its magnitude. These results offer a theoretical framework and practical insights for optimizing resource allocation and guiding policy in endemic disease management.

PMID:42234344 | DOI:10.1007/s11538-026-01663-x

Vet Res Commun. 2026 Jun 3;50(5):361. doi: 10.1007/s11259-026-11297-y.

ABSTRACT

This study evaluated the safety and feasibility of gasless laparoscopic cholecystectomy in dogs, identifying factors associated with surgical time and survival. Twenty-five dogs with symptomatic gallbladder disease-predominantly gallbladder mucocele (72.0%) and cholelithiasis-underwent cholecystectomy using a mechanical abdominal wall lift system. Variables including gallbladder volume, age, body condition score, and intraoperative complications were recorded. Statistical analyses employed Pearson’s chi-squared, Spearman’s correlation, regression analysis for surgical time predictors, and Kaplan-Meier survival analysis with log-rank tests. No significant association was found between breed and biliary condition. However, surgical time was significantly and positively correlated with body weight and body condition score (p < 0.001). Linear regression indicated that each 1 kg increase in body weight added approximately 4 min to the procedure. Gallbladder volume did not correlate with surgical duration. Survival analysis revealed that dogs with gallbladder mucocele had a significantly lower probability of overall survival compared to cholelithiasis (p = 0.014). The results demonstrate that the gasless laparoscopic cholecystectomy is a viable and safe alternative for canine patients, especially those at a high cardiorespiratory risk. While increased body weight is a critical predictor of prolonged surgery, the primary biliary pathology remains the most significant determinant of survival.

PMID:42234328 | DOI:10.1007/s11259-026-11297-y

Radiol Phys Technol. 2026 Jun 3. doi: 10.1007/s12194-026-01070-w. Online ahead of print.

ABSTRACT

This study compared a dose-volume histogram-based machine learning (ML) approach with a three-dimensional dose distribution-based convolutional neural network (CNN) approach for volumetric-modulated arc therapy planning in head and neck cancer (HNC). Sixty-five patients who underwent whole-neck radiotherapy were retrospectively analyzed; 55 cases were used for model training and 10 for independent testing. Treatment plans generated by the CNN-based framework and a commercial ML-based planning system (RapidPlan) were evaluated using dose-volume indices (DVIs) and blinded qualitative scoring. In the DVI analysis, the ML-based plans achieved significantly higher target coverage than both the CNN-based and clinical plans. In contrast, the CNN-based plans maintained a mean error of less than 2% relative to the clinical plans, indicating close agreement with the clinical standard. No statistically significant differences in organs-at-risk dose metrics were observed among the three approaches. In the blinded qualitative evaluation, mean scores were 4.7 ± 0.56, 4.0 ± 1.07, and 2.7 ± 0.90 for the clinical, CNN-based, and ML-based plans, respectively, with the ML-based plans receiving significantly lower scores. These findings indicate that differences in prediction methodology and optimization strategy influence final plan quality, particularly with respect to spatial dose characteristics. Three-dimensional dose distribution-based prediction may provide clinical advantages for automated radiotherapy planning in HNC.

PMID:42234324 | DOI:10.1007/s12194-026-01070-w

Mol Biol Rep. 2026 Jun 3;53(1):878. doi: 10.1007/s11033-026-12052-x.

ABSTRACT

BACKGROUND: Recent studies have emphasized the role of adenosine receptors (ADORs) in the malignant biological behaviors. Therefore, the expression and clinical significance of four subtypes of ADORs (ADORA1, ADORA2A, ADORA2B, and ADORA3) in ovarian tumors were analyzed.

METHODS AND RESULTS: The expression of ADORs in 24 pairs of ovarian tumor tissues and adjacent non-tumor tissues was measured by quantitative real-time PCR. The correlations between the investigated parameters and clinicopathological features were statistically tested. The diagnostic accuracy of ADORs was assessed using receiver operating characteristic curve analysis. Kaplan-Meier method was used to estimate the influence of ADORs expression on the prognosis of patients. Ovarian tumors showed higher expression of ADORA2A (1.5-fold), ADORA2B (2.2-fold), and ADORA3 (2.3-fold), but not ADORA1, compared to normal tissues. High expression of ADORA1 and ADORA2A was associated with younger age (≤ 48.5 years; P = 0.034) and clinical stage III-IV (P = 0.050), respectively. ADORA2B also showed moderate accuracy in ovarian tumors diagnosis (P = 0.001). Survival analyses further demonstrated that high expression of ADORA1 (P = 0.012) and ADORA2B (P = 0.027) was correlated with worse overall survival. Moreover, high ADORA3 expression (P = 0.042) was associated with poor post-progression survival.

CONCLUSIONS: Our results demonstrated that adenosine A2A, A2B, and A3 receptors were differentially expressed between ovarian tumors and paired non-tumor tissues, and that ADORs may be clinically useful biomarkers for diagnosis and outcome prediction in ovarian cancer.

PMID:42234312 | DOI:10.1007/s11033-026-12052-x

Int Urol Nephrol. 2026 Jun 3. doi: 10.1007/s11255-026-05218-w. Online ahead of print.

ABSTRACT

PURPOSE: To investigate the potential role of human papillomavirus (HPV) in early onset prostate cancer (PCa) through HPV-DNA detection and genotyping, and immunohistochemical evaluation of p16^INK4a expression.

METHODS: This retrospective cross-sectional study included patients diagnosed with PCa at ≤ 55 years of age between 2010 and 2021. Patients with a familial history of PCa, incomplete medical records, immunodeficiency, or insufficient tissue for molecular analysis were excluded. Formalin-fixed, paraffin-embedded (FFPE) prostate biopsy samples were analyzed for HPV-DNA using the HPV 3.5 LCD-Array Kit (Chipron GmbH, Berlin, Germany), a multiplex PCR-based assay targeting 32 HPV genotypes. Immunohistochemical staining for p16^INK4a was performed to assess its expression. Clinical data, including PSA levels, Gleason score, ISUP grade, and EAU risk group, were compared between HPV-positive and HPV-negative cases.

RESULTS: HPV-DNA was detected in 12 of 45 cases (26.7%), with genotype 62 being the most frequent. Multiple HPV genotypes were identified in three cases (6.7%). p16^INK4a immunopositivity was observed in 91.7% of HPV-positive tumors compared with 69.7% of HPV-negative tumors (p = 0.240). HPV-positive patients showed higher ISUP grades than HPV-negative patients (p = 0.029) and were more likely to be in intermediate or high-risk groups (p = 0.028). No significant differences were observed in PSA levels or Gleason scores.

CONCLUSION: The detection of HPV-DNA in a considerable proportion of early onset PCa specimens, together with the more frequent but not statistically significant p16^INK4a positivity in HPV-positive tumors, suggests a possible association with prostate tumor biology. However, the presence of low-risk HPV genotypes and the non-specific nature of p16^INK4a expression complicate the interpretation of a direct oncogenic role.

PMID:42234298 | DOI:10.1007/s11255-026-05218-w