Nevin Manimala

Endocrine. 2025 Aug 20. doi: 10.1007/s12020-025-04378-6. Online ahead of print.

ABSTRACT

PURPOSE: In recent years, endocrinology research has increasingly focused on machine learning (ML) applications. ML offers the possibility of utilizing large data sets and extracting imperceptible patterns. It might contribute in optimizing healthcare outcomes and unveiling new understandings of the intricate mechanisms of endocrine disorders. This review covers the basic aspects of ML and highlights specific areas of endocrinology with potential of ML application.

METHODS: This narrative review with a systematic literature search comprises studies on endocrine conditions with ML methods used in statistical analysis, published between January 2000 and December 2024.

RESULTS: A total of 1130 studies were analyzed. Thyroid-related research was the most prevalent, followed by studies concerning the pituitary, adrenal and parathyroid glands. ML applications included medical imaging analysis, tumor classification, treatment response prediction, complication risk estimation and identification of molecular markers.

CONCLUSION: ML has the potential to enhance the diagnosis, treatment and understanding of endocrine diseases. However, the use of ML is still limited by issues such as lack of model transparency, data imbalance and difficulties with clinical implementation. To enable safe and effective application of ML in endocrinology, further validation, interdisciplinary collaboration and standardized approaches are essential.

PMID:40833706 | DOI:10.1007/s12020-025-04378-6

JAMA Netw Open. 2025 Aug 1;8(8):e2527805. doi: 10.1001/jamanetworkopen.2025.27805.

ABSTRACT

IMPORTANCE: Cancer is a significant global health concern, with India ranking second in Asia and third in the world in terms of cancer incidence. Regular monitoring and updates on cancer statistics are vital for assessing the impact and burden of the disease and the effectiveness of cancer control measures.

OBJECTIVE: To measure the recent patterns and trends in cancer incidence and mortality across 43 geographic regions in India from 2015 to 2019 and to provide estimates for 2024.

DESIGN, SETTING, AND PARTICIPANTS: This cross-sectional study used data from 43 population-based cancer registries across India, covering varying periods between January 1, 2015, and December 31, 2019. Population at-risk data were obtained from the Census of India, and findings were assessed by registry area. Data were analyzed from May 1 to December 20, 2024.

MAIN OUTCOMES AND MEASURES: Number of cases, crude rates, and age-adjusted rates (per 100 000 population) for cancer incidence and mortality, estimated average annual percent change (AAPC) from time trends, and estimated cancer cases in India for 2024.

RESULTS: Incidence of 708 223 cases with 206 457 deaths from 43 population-based cancer registries were included. The lifetime risk of developing cancer in India was 11.0%, while Mizoram in the Northeastern region reported lifetime risks of 21.1% in males and 18.9% in females. The district of Aizawl reported the highest age-adjusted incidence rate (AAIR) in both males (256.1; 95% CI, 245.2-267.0) and females (217.2; 95% CI, 207.6-226.7). The most common cancers were oral, lung, and prostate in males and breast, cervical, and ovarian in females. Among metropolitan cities (defined as an urban agglomeration with a population of over 1 million), Delhi had the highest overall cancer AAIR for males (146.7; 95% CI, 145.1-148.3), while Srinagar recorded the highest AAIR for lung cancer (39.5; 95% CI, 35.8-43.2). Oral cancer showed significant increases in 14 population-based cancer registries (PBCRs) among males and 4 PBCRs among females; Ahmedabad Urban had an increase of 4.7% (95% CI, 2.9% to 6.6%) in males and 6.9% (95% CI, 4.1% to 9.7%) in females. The estimated AAPC in AAIR (all sites) showed a significant increase over time in Kamrup Urban in males (3.3%; 95% CI, 2.3%-4.3%) and Thiruvananthapuram Taluk in females (3.4%; 95% CI, 3.1%-3.8%). The estimated cancer incidence for 2024 was 1 562 099 cases; estimated cancer mortality, 874 404 cases.

CONCLUSIONS AND RELEVANCE: This cross-sectional study highlighted significant regional disparities in cancer incidence across India and the increasing cancer burden. The findings provide key insights for policymakers to enhance resource allocation and strengthen cancer control strategies nationwide.

PMID:40833697 | DOI:10.1001/jamanetworkopen.2025.27805

JAMA Netw Open. 2025 Aug 1;8(8):e2527934. doi: 10.1001/jamanetworkopen.2025.27934.

ABSTRACT

IMPORTANCE: Adolescents who experienced childhood socioeconomic deprivation report more eating disorder symptoms compared with their counterparts with higher socioeconomic status but may have more barriers in receiving diagnoses and accessing eating disorder services.

OBJECTIVE: To investigate the associations of childhood socioeconomic indicators with eating disorder symptoms across adolescence.

DESIGN, SETTING, AND PARTICIPANTS: This prospective cohort study used a population-based sample from the Avon Longitudinal Study of Parents and Children (ALSPAC). ALSPAC recruited pregnant women in the former region of Avon, United Kingdom, with expected delivery dates from April 1, 1991, to December 31, 1992. This study used follow-up data of the mother-offspring collected until 2010. The final analytical sample included children who were alive at 1 year of age and who had complete exposures, retaining 1 twin at random. Data were analyzed from October 1, 2022, to November 25, 2024.

EXPOSURES: The main exposures were parental income, education, occupation, financial hardship (range, 0-15; higher score indicates more hardship), reported by mothers between 32 weeks’ gestation and 47 months postpartum, and area-level deprivation, derived from the Office for National Statistics indicators linked to the participant’s residential post code at 32 weeks’ gestation.

MAIN OUTCOMES AND MEASURE: Primary outcomes were disordered eating, weight and shape concerns, and body dissatisfaction at ages 14, 16, and 18 years. Individual disordered eating behavior was a secondary outcome.

RESULTS: The sample included 7824 participants (4003 [51.1%] male). A 1-point increase in financial hardship was associated with increased odds of disordered eating (odds ratio [OR], 1.06; 95% CI, 1.04-1.10), an increase in weight and shape concerns (coefficient, 0.02 (95% CI, 0.01-0.04), and an increase in body dissatisfaction (coefficient, 0.22 (95% CI, 0.06-0.37). Lower parental education was associated with higher odds of disordered eating (OR, 1.80; 95% CI, 1.46 to 2.23).

CONCLUSIONS AND RELEVANCE: This cohort study using ALSPAC data found that eating disorder symptoms were more common in individuals experiencing socioeconomic deprivation. Potential socioeconomic inequalities in eating disorder presentation and diagnosis in clinical settings require further investigation. Reducing population-level socioeconomic inequalities could also aid eating disorder prevention.

PMID:40833695 | DOI:10.1001/jamanetworkopen.2025.27934

JAMA Netw Open. 2025 Aug 1;8(8):e2528529. doi: 10.1001/jamanetworkopen.2025.28529.

ABSTRACT

IMPORTANCE: Several large, randomized clinical trials have tested the efficacy of adding behavioral therapy to medical management (high-quality, low-intensity medical counseling) and buprenorphine treatment of opioid use disorder. These studies have consistently reported strong rates of treatment response overall, without a significant additive benefit of additional behavioral therapy.

OBJECTIVE: To address gaps in knowledge about additional behavioral therapy for patients receiving buprenorphine, including the association of additional behavioral therapy with retention and functional outcomes, and whether certain subgroups respond better to additional behavioral therapy.

DESIGN, SETTING, AND PARTICIPANTS: This study is a secondary analysis of 4 randomized clinical trials conducted in Connecticut, Southern California, and 10 other US sites between 2000 and 2011. Participants included adults with Diagnostic and Statistical Manual of Mental Disorders (Fourth Edition) opioid dependence. Analyses were conducted between January 2024 and July 2025.

EXPOSURE: Buprenorphine and varying levels of behavioral therapy, including standard medical management, physician management, physician management plus cognitive behavioral therapy, contingency management, contingency management plus cognitive behavioral therapy, standard medical management plus opioid dependence counseling, or no additional behavioral treatment.

MAIN OUTCOMES AND MEASURES: The main outcomes included weeks of buprenorphine retention and functioning across 7 domains (medical, employment and financial support, social and family, alcohol, drug, legal, and psychiatric), assessed using the Addiction Severity Index. Data on additional behavioral therapy (structured cognitive-behavioral and counseling approaches) combined with buprenorphine and medical management were harmonized to provide needed statistical power for considering moderation effects.

RESULTS: The combined sample consisted of 869 adults (mean [SD] age, 34.2 [10.4] years; 287 female [33%]). Results demonstrated that additional behavioral therapy was not associated with opioid-free weeks (mean [SD] number of opioid-free weeks, 7.16 [4.35]) compared with medical management and buprenorphine (mean [SD] number of opioid-free weeks, 7.00 [4.33]) (B = 0.28; 95% CI, -0.33 to 0.89; P = .37). Additional behavioral therapy was also not associated with greater buprenorphine retention (mean [SD] number of weeks of buprenorphine, 10.29 [3.21] out of 12) compared with medical management and buprenorphine (mean [SD] number of weeks of buprenorphine, 10.21 [3.15]) (B = 0.00; 95% CI, -0.43 to 0.43; P = .98). Measures of functioning indicated minimal change over the course of treatment, and there were no differences between randomized groups. No moderational effects of subgroups (eg, history of heroin use) were significant when correcting for multiple comparisons.

CONCLUSIONS AND RELEVANCE: In this secondary analysis of 4 randomized clinical trials, results highlighted the strong efficacy of buprenorphine treatment when combined with medical management for opioid use disorder. Although there was certainly room for improvement in outcomes-particularly functioning-trials of novel adjuncts for buprenorphine treatment may encounter statistical power challenges outperforming such a robust control condition.

TRIAL REGISTRATION: NCT00316277, NCT00591617, NCT00632151, NCT00023283.

PMID:40833692 | DOI:10.1001/jamanetworkopen.2025.28529

JAMA Cardiol. 2025 Aug 20. doi: 10.1001/jamacardio.2025.2698. Online ahead of print.

ABSTRACT

IMPORTANCE: Plasma levels of the gut microbiota-dependent metabolite trimethylamine N-oxide (TMAO) are associated with prevalent abdominal aortic aneurysms (AAA) in humans and fostering of AAA progression in animal models; therapeutic targeting of TMAO production blocks AAA progression and rupture in multiple mouse models. A blood biomarker that identifies individuals at risk for incident AAA development, accelerated AAA expansion, or recommendation for surgical AAA repair could be an asset for risk stratification.

OBJECTIVE: To determine whether TMAO is associated with risk for AAA development, rapid AAA expansion, and risk for recommended surgical intervention.

DESIGN, SETTING, AND PARTICIPANTS: This was a prospective cohort study using 2 independent clinical cohorts undergoing aorta imaging surveillance: a European cohort and a US cohort. Included in this study were patients undergoing serial imaging surveillance of the aorta and long-term outcome monitoring. Patients were recruited from single-center studies in Uppsala, Sweden, and Cleveland, Ohio. Study data were analyzed from October 2023 to May 2025.

EXPOSURES: Plasma TMAO concentrations measured by stable isotope dilution liquid chromatography with tandem mass spectrometry.

MAIN OUTCOMES AND MEASURES: The association of TMAO levels with AAA risk, fast-growing AAA (≥4.0 mm per year), and recommended surgical intervention (≥4.0 mm per year or ≥5.5 cm diameter).

RESULTS: The European cohort included 237 individuals (median [IQR] age, 65 [65-73] years; 211 male [89.0%]), and the US cohort included 658 individuals (median [IQR] age, 63 [57-70] years; 523 male [79.5%]). In the European cohort, elevated circulating TMAO was significantly associated with AAA risk independent of traditional risk factors and kidney function. Moreover, elevated TMAO predicted both greater risk for fast-growing AAA (adjusted odds ratio [aOR], 2.75; 95% CI, 1.20-6.79) and recommended surgical intervention (aOR, 2.67; 95% CI, 1.24-6.09). Similar patterns were observed in the US cohort and the combined European and US cohort, with heightened circulating TMAO corresponding with significantly increased adjusted risk for fast-growing AAA (US cohort: aOR, 2.71; 95% CI, 1.53-4.80; combined cohort: aOR, 2.30; 95% CI, 1.47-3.62) and recommended surgical intervention (US cohort: aOR, 2.73; 95% CI, 1.56-4.80; combined cohort: aOR, 2.41; 95% CI, 1.55-3.74). Addition of TMAO to base models containing traditional cardiovascular risk factors resulted in significant improvement in both risk estimation for fast-growing AAA and predicting recommended surgical intervention.

CONCLUSION AND RELEVANCE: Results of this cohort study suggest that elevated circulating TMAO levels were associated with increased risk of AAA and identified patients at heightened risk for fast-growing AAA and recommended surgical intervention. TMAO may help identify individuals who may benefit from more frequent surveillance imaging and early surgical intervention to prevent aortic dissection or rupture.

PMID:40833686 | DOI:10.1001/jamacardio.2025.2698

JAMA Psychiatry. 2025 Aug 20. doi: 10.1001/jamapsychiatry.2025.2110. Online ahead of print.

NO ABSTRACT

PMID:40833677 | DOI:10.1001/jamapsychiatry.2025.2110

Clin Transl Oncol. 2025 Aug 20. doi: 10.1007/s12094-025-03999-7. Online ahead of print.

ABSTRACT

PURPOSE: To evaluate the correlation between HER2 expression levels measured by HER2 mRNA using Oncotype DX and by immunohistochemistry (IHC) in hormone receptor-positive (HR+) and HER2-negative (HER2-) early breast cancer. In addition, we assessed whether low HER2 expression is associated with distinct clinicopathological characteristics and prognosis in our series.

METHODS: We conducted a retrospective study that included 500 patients diagnosed with stage I-III HR+/HER2- breast cancer who underwent surgery and had Oncotype DX recurrence score determined between 2009 and 2023 at Hospital Clínico San Carlos, Madrid, Spain. HER2 mRNA levels obtained through Oncotype DX were compared across IHC groups (HER2 0+, HER2 1+, HER2 2+/ISH-negative). Event-free survival (EFS) was analyzed according to HER2 expression.

RESULTS: Although HER2 mRNA levels increased with higher IHC HER2 categories, variability and overlap were observed between subgroups. Median Oncotype DX recurrence scores also rose slightly across HER2 IHC groups but did not reach statistical significance. EFS did not differ between HER2 expression levels.

CONCLUSIONS: We found that HER2 mRNA measurement by Oncotype DX provides a quantitative approach to assess HER2 expression. However, its results overlap within traditional IHC categories. While HER2-low classification may have therapeutic implications for new antibody-drug conjugates, its prognostic relevance appears limited. Further studies are needed to improve HER2 quantification methods for improved clinical decision-making.

PMID:40833671 | DOI:10.1007/s12094-025-03999-7

Ann Nucl Med. 2025 Aug 20. doi: 10.1007/s12149-025-02094-9. Online ahead of print.

ABSTRACT

PURPOSE: Transarterial radioembolization (TARE) is one of the local treatment options for primary and metastatic liver tumors. However, our knowledge regarding the safety of repeated TARE remains limited. In this study, we aimed to evaluate the safety of repeated transarterial radioembolization with multi-compartment dosimetry.

METHODS: In this retrospective single-center study, we analyzed the data of the patients who were treated with at least two separate sessions of radioembolization with ⁹⁰Y microspheres. Multi-compartment and voxel-wise dosimetry was performed for every treatment session and cumulative whole-liver normal tissue absorbed radiation dose (D_norm), V20-V100 values for whole-liver normal tissue were calculated. Toxicity was assessed with Common Terminology Criteria for Adverse Events (CTCAE) grading system for alanine aminotransferase (ALT)/aspartate aminotransferase (AST)/bilirubin levels and International Normalized Ratio (INR) before and after each treatment. In addition, albumin-bilirubin (ALBI) scores, grades, and changes in ALBI score (ΔALBI) were recorded. Difference between the ALBI scores before and after the treatment was compared with Wilcoxon tests, and relationships between ΔALBI and dosimetric variables were compared using linear regression analyses.

RESULTS: A total of 24 patients (6 males, 18 females; median age: 57 years) were included in the analysis. The most common diagnosis was colorectal carcinoma liver metastases (46%). Seventeen patients (71%) underwent two TARE treatments, five (21%) underwent three, and two (8%) underwent four. The median interval between the first and second treatments was 138 days (range: 34-782), and between the second and third treatments was 210 days (range: 72-435). No CTCAE Grade 3 or 4 toxicities were observed. ALBI score analysis revealed no significant changes after the first two treatments, but a significant difference was noted after the third treatment (P = 0.043), with one patient progressing to ALBI Grade 3 with significant hypoalbuminemia. No significant relationship was found between ΔALBI and treatment intervals. ALT/AST elevations were mostly transient and mild, with only one case of Grade 2 hepatotoxicity in each of the first two treatments. In patients treated with glass microspheres in their first two treatments (n = 12), a significant linear correlation was found between cumulative D_norm and ΔALBI (R² = 0.512, P = 0.007). Cumulative dose-volume histogram parameters, particularly V30, V40, and V50, showed significant correlations with ΔALBI. However, in patients treated with resin microspheres (n = 6), no statistically significant relationship was observed between cumulative D_norm and ΔALBI (P = 0.718).

CONCLUSION: Repeated TARE with a multi-compartment personalized dosimetric approach appears to be safe for the first two cycles, with limited low-grade toxicity. However, significant increase in ALBI scores after the third treatment was observed. ALBI score changes after second TARE were associated with cumulative liver radiation exposure in patients treated with glass microspheres. Larger studies are needed to further explore predictors of hepatotoxicity in repeated TARE.

PMID:40833652 | DOI:10.1007/s12149-025-02094-9

J Mol Model. 2025 Aug 20;31(9):251. doi: 10.1007/s00894-025-06481-x.

ABSTRACT

CONTEXT: hRPE65 is an essential enzyme in the retinoid visual cycle. Numerous missense variants of hRPE65 have been linked to retinal disorders, such as retinitis pigmentosa and Leber congenital amaurosis. Moreover, many hRPE65 missense mutations are currently classified as variants of uncertain significance (VUS) due to insufficient evidence for a definitive pathogenicity classification. Addressing this limitation is critical for enabling accurate diagnoses and identifying suitable candidates for gene therapy. For this reason, we developed a hRPE65-tailored computational strategy, based on a consensus of multiple in silico pathogenicity predictions, enabling a rapid and reliable evaluation of the potential pathogenic effect of over 200 hRPE65 VUS. The analysis provided valuable insights to support the reclassification of these variants and assist clinicians in assessing their suitability for gene therapy.

METHODS: In this study, we optimized our recently developed ConPath approach, which combines variant pathogenicity predictions from 19 different computational tools. In particular, we expanded the pool of predictive tools combined in the approach to 27, incorporated 3D-based methods that employ structural information for their prediction, and we refined the statistical framework for selecting the most reliable tools within an extended pool of more than 70 different methods. The tools were assessed based on their ability to discriminate pathogenic from benign hRPE65 missense mutations using an updated and expanded dataset of known hRPE65 variants. The resulting enhanced strategy, ConPath 2.0, was applied to the 210 hRPE65 VUS reported in the ClinVar database.

PMID:40833643 | DOI:10.1007/s00894-025-06481-x

World J Urol. 2025 Aug 20;43(1):505. doi: 10.1007/s00345-025-05873-1.

ABSTRACT

PURPOSE: This study focuses on the detection of human papillomavirus (HPV) in genital samples from heterosexual men, with or without HPV-like lesions, using molecular biology techniques for diagnosis and genotyping of the virus.

METHOD: A retrospective observational study was conducted with 294 male patients who visited a laboratory for molecular testing, with a presumptive clinical-epidemiological diagnosis of HPV infection, without prior HPV disease or vaccination. Samples were analyzed using Polymerase Chain Reaction (PCR) and Restriction Fragment Length Polymorphism (RFLP) techniques.

RESULTS: Detection of HPV-infected men was 50.8%, with significant variability in incidence depending on the anatomical site of sampling. Fourteen high-risk HPV types were identified, along with the presence of multiple subtypes in several patients.

CONCLUSION: This study provides valuable insights into HPV incidence in men, the most prevalent genotypes, and their correlation with lesion presence. These findings may aid in developing prevention, vaccination, and control strategies for HPV in men.

PMID:40833638 | DOI:10.1007/s00345-025-05873-1