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Gene-Environment Interactions in Childhood Asthma: From Prenatal Exposures to Targeted Interventions

FASEB J. 2026 Jul 15;40(13):e72094. doi: 10.1096/fj.202505048R.

ABSTRACT

Asthma is one of the most common chronic respiratory diseases affecting both children and adults worldwide. Its pathogenesis is driven by complex interactions between genetic susceptibility and environmental exposures. Investigating gene-environment (G × E) interactions holds significant potential to elucidate the regulatory genetic architecture underlying individual responses to environmental risk factors in childhood asthma. In this review, we systematically summarize the environmental exposure factors during prenatal and postnatal periods and analyze their independent effects on the risk of childhood asthma. Secondly, we explore the role of G × E interactions in asthma from three perspectives: statistical interaction, mechanistic interaction, and epigenetic-mediated interaction. Finally, we evaluate current treatment and intervention strategies, distinguish established recommendations for the general population from emerging and exploratory methods, and point out existing limitations. Our analysis reinforces that investigating G × E interactions is a robust approach for uncovering the molecular mechanisms underlying childhood asthma. Despite substantial technical challenges and unresolved questions regarding generalizability and heterogeneity, such investigative strategies are expected to enhance our understanding of asthma endotypes and the development of more effective, precision-based preventive and therapeutic interventions.

PMID:42384431 | DOI:10.1096/fj.202505048R

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Nevin Manimala Statistics

Lumpectomy Margins and Local Recurrence in DCIS: Results From the NRG Oncology/NSABP B-35 Randomized Clinical Trial

JAMA Surg. 2026 Jul 1. doi: 10.1001/jamasurg.2026.2340. Online ahead of print.

ABSTRACT

IMPORTANCE: The NRG Oncology research organization and NSABP B-35 randomized clinical trial prospectively collected margin width data on postmenopausal women with hormone receptor (HR)-positive ductal carcinoma in situ (DCIS) who underwent lumpectomy, whole-breast irradiation (WBI), and randomly assigned adjuvant anastrozole or tamoxifen therapy. This permitted analysis of outcomes per margin width.

OBJECTIVE: To analyze the effect of margin width on ipsilateral breast tumor recurrence (IBTR).

DESIGN, SETTING, AND PARTICIPANTS: NSABP B-35 was a phase 3, double-blind, randomized clinical trial in which patients were randomized to either 5 years of tamoxifen or anastrozole. Postmenopausal women with HR-positive DCIS and tumor-free margins were eligible. Enrollment was from January 6, 2003, to June 15, 2006, in academic and community hospital members of the NSABP. Study data were analyzed from July 2024 to April 2025.

INTERVENTIONS: There were no specific interventions based on lumpectomy margin width.

MAIN OUTCOMES AND MEASURES: Lumpectomy margin width data were prospectively collected within 3 months of randomization. A pathology form classified margins as positive (ink on tumor), close (<1 mm), or negative (≥1 mm). For the negative margin subgroup, closest margin width was stated separately. Thus, an ancillary analysis using 1-mm and 2-mm margin width partitions was performed.

RESULTS: A total of 3104 postmenopausal women (mean [SD] age, 61 [7.8] years) were enrolled in NSABP B-35. In an ancillary analysis, 2707 patients were included in the 1-mm margin width partition group, and 2546 patients were included in the 2-mm margin width partition group. IBTR was the most common first event, occurring in 90 of 2707 patients (3.3%): 24 of 502 patients (4.8%) with a margin width less than 1 mm and 66 of 2205 patients (3.0%) with a margin width greater than or equal to 1 mm. Ten-year unadjusted cumulative incidence of IBTR events was 5.6% vs 4.0% for margins less than 1 mm vs margins greater than or equal to 1 mm (P = .04). Using 2 mm as the discriminant threshold for margin width, 39 of 879 patients (4.4%) with margins less than 2 mm and 49 of 1667 patients (2.9%) with margins greater than or equal to 2 mm experienced an IBTR first. Ten-year unadjusted cumulative incidence of IBTR events with margins less than or equal to 2 mm was 5.3% vs 3.8% for those with margins greater than 2 mm (P = .05). In models adjusting for other patient and tumor factors, margin width was not a significant predictor of IBTR risk (2-mm threshold hazard ratio, 1.33; 95% CI, 0.86-2.06).

CONCLUSIONS AND RELEVANCE: Results of this ancillary analysis of the NSABP B-35 trial show that absolute differences in IBTR rates using margin width groupings of less than 1 mm or greater than or equal to 1 mm and margin width groupings of less than 2 mm or greater than or equal to 2 mm in postmenopausal women with HR-positive DCIS receiving lumpectomy, WBI, and adjuvant endocrine therapy were small. Omission of reexcision lumpectomies based on margin widths of less than 1 mm or less than 2 mm can be reconsidered in appropriate patients.

TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT00053898.

PMID:42384406 | DOI:10.1001/jamasurg.2026.2340

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Nevin Manimala Statistics

Costs, Charges, and Revenue of Hospital Operating Rooms in California

JAMA Surg. 2026 Jul 1. doi: 10.1001/jamasurg.2026.2355. Online ahead of print.

ABSTRACT

IMPORTANCE: The operating room (OR) is the most resource-intensive setting in the hospital, making accurate OR financial metrics essential for value-based initiatives and cost-effectiveness analyses. However, prior estimates of OR time have been rendered likely obsolete by the COVID-19 pandemic, sustained inflation, and hospital consolidation, and conflation of 3 financial parameters-costs, charges, and revenue-has led to misapplication of these estimates.

OBJECTIVES: To estimate the cost of 1 minute of OR time in California hospitals, assess trends over time by hospital ownership and teaching status, and provide benchmarks for OR charges and revenue.

DESIGN, SETTING, AND PARTICIPANTS: This longitudinal cross-sectional study examined California Hospital Annual Disclosure Reports for fiscal years (FYs) 2014 to 2022 from short-term general and specialty care hospitals in California. Data were analyzed from January 24 to March 13, 2026.

MAIN OUTCOMES AND MEASURES: The primary outcome was mean costs, charges, and revenue per minute of OR time, stratified by hospital ownership and teaching status. Costs were further divided into direct and indirect components. Descriptive statistics summarized hospital characteristics and financial measures.

RESULTS: The study included 278 hospitals that provided California Hospital Annual Disclosure Reports for FY 2022. Of these, 164 (59.0%) were not-for-profit hospitals, 75 (27.0%) were for-profit hospitals, and 39 (14.0%) were government owned hospitals; 34 (12.2%) were teaching hospitals. The mean (SD) cost of OR time across all hospitals was $57.71/min ($24.09/min), representing a 54% increase from FY 2014 with an annual increase of 5.24% (95% CI, 4.63%-5.82%). Direct costs accounted for 56.6% of total costs ($32.56 of $57.53), with wages and benefits comprising approximately two-thirds of direct costs. The mean (SD) charge was $295.09/min ($148.23/min) and the mean (SD) revenue was $66.31/min ($31.30/min). Government-owned hospitals had the lowest charges, highest costs, and intermediate revenues, illustrating that these 3 measures are not interchangeable.

CONCLUSIONS AND RELEVANCE: In this cross-sectional study, the mean cost of OR time in California hospitals was $57.71/min in FY 2022, establishing an updated benchmark for surgical cost analyses. Additionally, benchmarks were established for OR revenue ($66/min) and charges ($295/min). Appropriate use of the different financial metrics along with accurate values is essential for valid cost-effectiveness analyses and value-based surgical care initiatives.

PMID:42384389 | DOI:10.1001/jamasurg.2026.2355

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Associations of marital status with well-being and career intentions among medical residents: a national survey in Japan

Acad Med. 2026 Jul 1:wvag209. doi: 10.1093/acamed/wvag209. Online ahead of print.

ABSTRACT

PURPOSE: Marital status has been associated with the well-being and career decisions of physicians; however, its role during residency remains underexplored, particularly in Japan. This study aimed to examine the association among marital status, psychological well-being, and intended specialty choice among postgraduate medical residents in Japan, with a focus on sex differences.

METHOD: The authors conducted a nationwide cross-sectional survey in January 2023 of postgraduate second-year residents in Japan immediately after the 2022 General Medicine In-training Examination (GM-ITE). Participants completed the survey and provided complete data on their marital status and outcome measures. The primary outcomes included depressive symptoms (assessed using the Patient Health Questionnaire-2), burnout symptoms, job satisfaction, and work-related stress (assessed using the Mini-Z 2.0) as well as gender role attitudes and intended specialty. The authors estimated adjusted prevalence ratios (PRs) using modified Poisson regression with generalized estimating equations.

RESULTS: Among 2,721 residents included in the analysis (mean age, 27.7 years; 879 [32.3%] female), 551 (20.2%) were married, of whom 282 (51.2%) had physician spouses. Depressive symptoms were most common among unmarried residents (613/2,170 [28.2%]) and least common among those married to physicians (50/282 [17.7%]; P < .001). In adjusted analyses, being married to a physician was associated with a reduced depressive symptoms prevalence (PR, 0.62; 95% confidence interval [CI], 0.48-0.81) and increased job satisfaction (PR, 1.09; 95% CI, 1.02-1.18). Marital status showed no statistically significant association with burnout symptoms or work-related stress, and no statistically significant specialty preferences differences were observed according to marital status. Female residents, particularly those married to physicians, were more likely to disagree with traditional gender roles than their male counterparts.

CONCLUSIONS: Among Japanese medical residents, marriage-particularly to another physician-was associated with fewer depressive symptoms and greater job satisfaction, whereas marital status was not associated with intended specialty choice.

PMID:42384362 | DOI:10.1093/acamed/wvag209

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Optimization of hypovascular liver lesion detectability in dual-energy CT using deep learning image reconstruction: a phantom study for potential iodine dose reduction

Eur Radiol Exp. 2026 Jul 1;10(1):104. doi: 10.1186/s41747-026-00759-2.

ABSTRACT

OBJECTIVE: To determine the optimal low-keV level using deep learning image reconstruction (DLIR) that maximizes lesion detectability, and to assess the potential for iodinated contrast media (ICM) reduction based on detectability improvements across varying patient body habitus.

MATERIALS AND METHODS: An abdominal phantom was scanned using a standard thoraco-abdomino-pelvic dual-energy computed tomography (DECT) protocol during the portal venous phase, with three rings inserted simulating different body habitus. Virtual monoenergetic images (VMI) were reconstructed from 40 to 70 keV in 10 keV increments using adaptive statistical iterative reconstruction-V (ASIR-V) 50% and high-strength DLIR (DLIR-H). Contrast enhancement was quantified, spatial resolution was evaluated with the task-based transfer function, and noise characteristics were analyzed using the noise power spectrum. Low-contrast lesion detectability (5-10 mm) was assessed using an anthropomorphic model observer.

RESULTS: Compared to ASIR-V, DLIR-H provided equivalent contrast, reduced image noise, and improved spatial resolution. All lesion sizes with DLIR-H were technically detectable under all conditions. The reconstruction at 40 keV demonstrated the highest detectability of hypovascular lesions under all conditions. However, a decrease in detectability was observed in the large phantom relative to the small and medium phantoms, resulting in a reduced theoretical potential for iodine dose reduction. The theoretical potential for iodine dose reduction using 40 keV with DLIR-H is at least 31.3% based on the phantom-based model.

CONCLUSION: Under phantom conditions, 40 keV with DLIR-H shows superior detectability of hypovascular lesions under all conditions, suggesting the theoretical possibility of reducing iodine load by up to 31.3%, based on modeled detectability performance.

RELEVANCE STATEMENT: Based on a phantom-derived model, the combination of 40-keV VMI reconstruction with DLIR-H suggests the potential for more than 30% ICM reduction in oncologic body CT, a finding that warrants confirmation in clinical studies.

KEY POINTS: Based on a phantom-derived model 40 keV VMI with DLIR-H achieved the highest detectability of hypovascular liver lesions. This approach enabled a 31.3% ICM volume reduction. Larger body habitus limits ICM volume reduction optimization margins.

PMID:42384360 | DOI:10.1186/s41747-026-00759-2

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GeneQuantify: a web-based tool for qPCR gene expression and copy number variation analysis

Mol Cell Biochem. 2026 Jul 1. doi: 10.1007/s11010-026-05621-y. Online ahead of print.

ABSTRACT

Quantitative polymerase chain reaction (qPCR) is an indispensable tool in clinical biochemistry laboratories for gene expression and copy number variation (CNV) analyses. However, the interpretation of qPCR data including normalization, rigorous statistical testing, and professional visualization typically requires advanced bioinformatics expertise. This study aimed to develop a user-friendly, web-based platform that integrates robust statistical frameworks and quality control modules for streamlined and standardized qPCR data evaluation. GeneQuantify is freely accessible at https://GeneQuantify.streamlit.app/ and its source code is openly available at https://github.com/burhanettiny/GeneQuantify (GPL-3.0 license). GeneQuantify, a web-based application developed using Python and Streamlit, allows for the input of target and reference gene Cq values via manual entry or direct import from spreadsheet software or standardized RDML/RDES file formats. The platform automatically calculates ΔCq, ΔΔCq, and relative expression levels using the 2^(-ΔΔCq) method. Integrated features include multi-reference gene normalization (geNorm), automated outlier detection (Grubbs’ test or Interquartile Range), and amplification efficiency correction (Pfaffl model). ΔCt values are subjected to normality (Shapiro-Wilk) and variance homogeneity (Levene’s) testing to ensure statistical validity. The platform features an automated statistical decision pipeline (Shapiro-Wilk → Levene → t/Welch/Mann-Whitney/ANOVA/Kruskal-Wallis) with Bonferroni and Benjamini-Hochberg FDR corrections. A six-language interface (Turkish, English, German, French, Spanish, and Arabic) ensures international accessibility. Platform accuracy was validated against manual Excel-based calculations across seven predefined test scenarios, yielding consistent results in all cases. GeneQuantify provides a highly accessible, integrated qPCR analysis environment that consolidates automated calculations, quality control, statistical decision-making, and visualization. By aligning with MIQE guidelines and offering RQ-based automated statistical selection, the platform enhances reproducibility, transparency, and workflow efficiency in molecular research, clinical biochemistry, and educational settings.

PMID:42384344 | DOI:10.1007/s11010-026-05621-y

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Screening and Evaluation of Post-stroke Dysphagia: Insights from Neurology, Artificial Intelligence and Data Science-A Scoping Review

Ann Biomed Eng. 2026 Jul 1. doi: 10.1007/s10439-026-04267-7. Online ahead of print.

ABSTRACT

Post-stroke dysphagia (PSD) affects approximately 42% of acute stroke patients, increasing hospitalization costs and length of stay. Early identification improves outcomes, yet many patients-especially in low-resource settings-lack access to gold-standard evaluations. This scoping review explores the integration of artificial intelligence (AI) and data science-defined as the interdisciplinary use of computational methods, statistical modeling, and machine learning to extract clinically meaningful patterns from biomedical data-in PSD screening and assessment. We synthesize evidence from bedside screening instruments, acoustic voice analyses, and emerging AI-driven models for dysphagia and aspiration risk stratification, critically appraising limitations related to small datasets, overfitting risk, and the need for external validation. Traditional tools like the water swallow test show high sensitivity but varying specificity; recent studies support augmenting these with voice-based biomarkers such as post-swallow wet voice, jitter, and shimmer. While wet voice as a standalone marker has limited sensitivity (8-29%), its high specificity (75-94%) within multimodal approaches justifies continued investigation. AI models trained on acoustic parameters have demonstrated strong performance in detecting penetration-aspiration events, while mobile and voice-based platforms may expand diagnostic reach, pending further validation. We also review optimal screening timing, emphasizing assessment within 24 h of stroke onset with repeated evaluations for high-risk patients. Future directions advocate multimodal, patient-centered approaches combining wearable biosensors, cloud-based analytics, and culturally adapted algorithms, while addressing implementation challenges including infrastructure requirements, digital literacy, workflow integration, and ethical considerations. The convergence of clinical expertise and computational technologies presents a promising path to equitable, scalable, and precise dysphagia care.

PMID:42384315 | DOI:10.1007/s10439-026-04267-7

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Identification of Acantamoeba isolated from water resources located in the northwest of Iran by using the high-resolution melting analysis assay

Int Microbiol. 2026 Jul 1. doi: 10.1007/s10123-026-00857-6. Online ahead of print.

ABSTRACT

BACKGROUND: Free-living amoebae (FLA), such as Acanthamoeba, are protozoan parasites that take advantage of opportunities with a widespread distribution in various environmental sources, such as a wide range of water sources. The amoeba can accidentally infect individuals and cause a variety of diseases, including amoebic encephalitis and keratitis, in both immunocompetent and immune-deficient individuals. The amoeba can act as reservoirs and carriers for pathogenic microorganisms, increasing the risk of pathogenicity in humans. The objective of this research was to identify the genotypes, besides in addition to the species of the FLA, in water sources in Qazvin province using high-resolution melting analysis (HRM).

METHODS: A total of 44 DNA isolates from FLA, including samples from swimming pools irrigation canals, and drinking water, were analyzed for the 18SrDNA gene using HRM. The data was evaluated using Chi-square test and Fisher’s exact tests.

RESULTS: The Molecular analysis revealed that 79.5% of the isolates were of the T3 genotype, 6.9% were of the T4 genotype of Acanthamoeba, and 13.6% were identified as Protoacantamoeba bohemica species. The statistical analysis exhibited a significant difference among the contamination and water source.

CONCLUSION: As water sources directly related to the public health, this study recommends paying close attention to treating water sources and utilizing new and accurate molecular methods to identify the potential pathogenic amoeba.

PMID:42384305 | DOI:10.1007/s10123-026-00857-6

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Provision of medication prescription in a fracture liaison service did not diminish during COVID

Arch Osteoporos. 2026 Jul 1;21(1):98. doi: 10.1007/s11657-026-01730-9.

ABSTRACT

We examined the association of COVID time periods and equity-related variables with pharmacotherapy in a large jurisdiction fracture liaison service (FLS). We did not observe a significant association between COVID time periods and medication prescription after adjusting for all covariates. This highlights another potential success of the FLS model.

PURPOSE: Our objective was to examine the impact of COVID on bone-active medication prescription in a fracture liaison service (FLS), after adjusting for fracture risk status and equity-related variables.

METHODS: We conducted a logistic regression analysis with medication prescription (prescription by a bone health specialist or primary care provider) as the outcome. The model included covariates COVID time periods (T1: “pre-COVID” (n = 2796); T2: “during COVID” (n = 1575); T3: “COVID recovery” (n = 2208)), fracture risk status (high risk/not high risk) and equity-related variables (sex, age, marital status, living arrangement, education status, geographic location, and presence of comorbidities). Goodness of fit was assessed with the area under the receiver operating characteristic curve (AUC) and the Hosmer and Lemeshow test.

RESULTS: Fracture risk status was the primary driver of treatment with high-risk patients 7.8 times more likely to receive a medication prescription compared to patients who were not high risk, after adjusting for all covariates (OR = 7.80 [95% CI 6.91, 8.79]). COVID time period was not statistically significant. Female patients, those married or in a common-law relationship, living alone, or residing in urban areas were more likely to be prescribed medication. The model had good prediction power and fit the data well (AUC: 0.77; Hosmer-Lemeshow test p-value: 0.83).

CONCLUSION: Among patients reached by the FLS, COVID time period was not significantly associated with medication prescription, although program reach decreased at T2 and T3. Fracture risk status, sex, marital status, living arrangement, and geographic location were significantly associated with medication prescription.

PMID:42384300 | DOI:10.1007/s11657-026-01730-9

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Management of isolated gingival recession defects using platelet rich fibrin and amnio-chorion membrane in coronally advanced flap: an in-vivo study

Saudi Dent J. 2026 Jul 1;38(7):93. doi: 10.1007/s44445-026-00202-7.

ABSTRACT

Gingival recession is a highly prevalent mucogingival condition that can significantly compromise oral health and esthetics. Patients commonly suffer from dentinal hypersensitivity, root caries, poor esthetics, discomfort during brushing, and in severe cases tooth mobility or tooth loss, ultimately affecting their quality of life. To compare the effectiveness of Platelet Rich Fibrin (PRF) and Amnio-Chorion Membrane (ACM) with Coronally Advanced Flap (CAF) to manage the case of isolated gingival recession defects (GRD). The study is a split-mouth randomised trial that included 13 patients (n = 26) with bilateral Miller Class 1 or 2 maxilla anterior and premolar recession of the gingiva. The randomizing of locations was also done to 13 sites in each group of either Group I (CAF+ PRF, n = 13) or Group II (CAF +ACM, n = 13). At 6 months follow-up, plaque Index (PI), Gingival Index (GI), Probing pocket depth (PPD), gingival recession depth (GRD), Clinical attachment level (CAL), Keratinized gingiva width (WKG), Percentage of root coverage, and root coverage Esthetic score (RES) were measured. All data were analyzed in the SPSS v21.0 software; paired t-tests and unpaired t-tests were used for comparing the intragroup and intergroup respectively. The level of statistical significance was defined as p < 0.05. At 6 months, statistically significant improvements in PRF and CAM in all clinical parameters was seen. Root coverage of Group I was 78.84 ± 19.13 and Group II was 74.99 ± 15.59. Intergroup comparisons showed no statistically significance in clinical outcome, RES or root coverage percentage (p > 0.05). PRF and ACM had both positive outcomes on gingival thickness, WKG, and CAL. PRF or ACM resulted in significant improvement in clinical periodontal parameters, root coverage, and esthetic outcomes, with no statistically significant difference between the two groups.

PMID:42384299 | DOI:10.1007/s44445-026-00202-7