Category: Nevin Manimala

Ren Fail. 2026 Dec;48(1):2700069. doi: 10.1080/0886022X.2026.2700069. Epub 2026 Jul 17.

ABSTRACT

Protein-energy wasting (PEW) is common in incident hemodialysis patients and linked to poor outcomes. The uric acid/HDL-cholesterol ratio (UHR) and intact parathyroid hormone (iPTH) relate to metabolic, inflammatory, and nutritional disturbances, but their value for predicting PEW in incident hemodialysis is unclear. This retrospective multicenter study included 863 incident hemodialysis patients. PEW was defined according to the International Society of Renal Nutrition and Metabolism criteria. UHR and iPTH were evaluated using ROC analysis, multivariable logistic regression, and ten machine learning models. Restricted cubic spline, mediation, and trajectory analyses were performed, with SHAP for interpretability. PEW was identified in 59.2% of patients. Feature selection across four machine learning approaches consistently identified UHR, iPTH, and eGFR as key predictors. Higher baseline and cumulative UHR were independently associated with a lower risk of PEW. Trajectory analysis showed that both rapidly increasing and decreasing UHR patterns with higher mean levels were linked to the lowest PEW risk. Nonlinear associations were observed, with an inverted U-shaped relationship between UHR and PEW and an S-shaped relationship between iPTH and PEW. Mediation analysis indicated that iPTH accounted for approximately 10-13% of the association between UHR and PEW. Among all models, XGBoost achieved the best performance (AUC = 0.801). A web-based Shiny tool was developed for individualized PEW risk assessment. UHR and iPTH were associated with PEW risk within specific ranges. Machine learning models integrating these markers showed favorable predictive performance and may assist individualized risk assessment in clinical practice.

PMID:42464731 | DOI:10.1080/0886022X.2026.2700069

Yi Chuan. 2026 Jul;48(7):701-713. doi: 10.16288/j.yczz.25-201.

ABSTRACT

Suicide is defined as an intentional act of ending one’s own life. Suicide attempt (SA) is a significant risk factor for suicide death. Research on SA has progressed from socio-psychological perspectives to the molecular and genetic levels. While the biological mechanisms underlying genome-wide association studies (GWAS) identified risk loci remain largely unclear. To investigate the potential risk mechanisms, we constructed a systematic analytic pipeline using brain protein quantitative trait locus (pQTL) datasets (Banner, N=152; ROSMAP, N=376), a brain expression quantitative trait locus (eQTL) datasets (N=452), and SA GWAS summary statistics (N_case=35,786, N_control=779,392). We performed proteome-wide association study (PWAS), Mendelian randomization (MR), Bayesian colocalization analysis, transcriptome-wide association study (TWAS), and multi-marker analysis of genomic annotation (MAGMA) to systematically identify and screen for novel genetically supported candidate proteins related to the biological mechanism of SA in the brain. For functional annotation, we used the GeneMANIA to bulid a functional prediction network integrating co-expression, physical interactions, and pathway colocalization to identify core proteins. PWAS identified three brain proteins whose genetically predicted abundance was significantly associated with SA. Among them, GMPPB was prioritized as putative causal protein, supported by MR analysis (false discovery rate, FDR<0.05) and Bayesian colocalization analysis (posterior probability PPH₄≥0.8). Specifically, higher genetically predicted GMPPB protein levels were associated with increased risk of SA. Although our analyses primarily relied on datasets from European-ancestry populations, the shared genetic architecture across populations and the generalizability of genome-wide data analytical approaches suggest that our findings may still provide useful insights into the biological mechanisms underlying SA and help inform the development of intervention strategies and genetic counseling in Chinese populations.

PMID:42464726 | DOI:10.16288/j.yczz.25-201

Int J Urol. 2026 Jul;33(7):e70549. doi: 10.1111/iju.70549.

ABSTRACT

OBJECTIVES: This post-marketing surveillance study evaluated the real-world safety and effectiveness of cabozantinib in Japanese patients with advanced renal cell carcinoma (aRCC).

METHODS: This prospective, observational study enrolled patients with histologically or cytologically confirmed aRCC across 102 sites in Japan. Patients received cabozantinib as monotherapy or in combination with nivolumab according to approved label regimens and were monitored for 26 weeks. The primary outcome was the incidence of adverse drug reactions (ADRs) related to hepatic failure/dysfunction and pancreatitis. Secondary outcomes included grade 3 or higher ADRs, treatment discontinuation due to ADRs, and investigator-assessed objective response rate (ORR) using Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1.

RESULTS: Of 388 enrolled patients, 385 were included in the analysis (median age, 71.0 years; 70.1% men). Patients receiving monotherapy (n = 322) and those receiving combination therapy (n = 63) reported ADRs related to hepatic failure/dysfunction (16.15% and 25.40%), pancreatitis-related ADRs (2.80% and 4.76%), grade 3 or higher ADRs (24.84% and 38.10%), and ADRs leading to treatment discontinuation (13.98% and 30.16%), respectively. The most common grade 3 or higher ADRs were hypertension (3.73%), reduced appetite (3.11%), and hand-foot syndrome (3.11%) in the monotherapy group, and diarrhea (4.76%) in the combination therapy group. The ORR was 32.9% for patients receiving monotherapy and 41.3% for those receiving combination therapy.

CONCLUSIONS: Cabozantinib, as monotherapy or in combination with nivolumab, demonstrated safety and effectiveness in Japanese patients with aRCC in real-world settings, consistent with previous literature. No new safety concerns were identified. These findings support the use of cabozantinib-based regimens in Japanese clinical practice.

TRAIL REGISTRATION: Japan Registry of Clinical Trials (JRCT), registration number: jRCT2031210003.

PMID:42464667 | DOI:10.1111/iju.70549

Catheter Cardiovasc Interv. 2026 Jul 16. doi: 10.1002/ccd.70760. Online ahead of print.

ABSTRACT

BACKGROUND: Neoatherosclerosis is a major mechanism of late and very late stent failure. While plaque rupture (PR) has traditionally been considered the dominant substrate, the prevalence and characteristics of other neoatherosclerotic plaque complications remain insufficiently defined. We aimed to investigate the morphological and clinical differences between neoatherosclerotic PR and plaque erosion (PE) using optical coherence tomography (OCT).

METHODS: This retrospective single-center study included patients with stent failure undergoing OCT-guided percutaneous coronary intervention between January 2020 and December 2025. Patients with neoatherosclerosis-related stent failure were classified according to OCT findings as PR or PE. Clinical presentation, angiographic characteristics, OCT-derived plaque morphology, and long-term outcomes were compared.

RESULTS: Among 103 screened patients, 44 met the inclusion criteria; 28 had PR, 14 had PE and 2 had instent eruptive calcific nodule. PR patients more frequently presented with STEMI and demonstrated significantly higher levels of macrophage infiltration (57.1% vs. 23.1%, p = 0.043), cholesterol crystals (60.7% vs. 28.6%, p = 0.050), lipid arc ≥ 180° (80% vs. 42.9%, p = 0.031), and thin-cap fibroatheroma (35.7% vs. 7.1%, p = 0.048). In contrast, layered plaque was markedly more prevalent in PE (92.9% vs. 48.3%, p = 0.004), and minimal in-stent lumen area was smaller in PE lesions (p = 0.039). Postprocedural thrombus protrusion was significantly more common in PR (81% vs. 27.5%, p = 0.005). Although not statistically significant, all-cause and cardiac mortality were numerically higher in PR patients during follow-up.

CONCLUSIONS: Neoatherosclerotic PR and PE represent distinct mechanisms of stent failure with different inflammatory profiles, plaque morphology, and clinical presentations. PR is associated with higher lipid burden and inflammatory activity, whereas PE is characterized by layered neointima and lower inflammatory features. OCT-based plaque characterization may improve risk stratification and support personalized treatment strategies in late stent failure.

PMID:42464582 | DOI:10.1002/ccd.70760

Diagn Interv Radiol. 2026 Jul 17. doi: 10.4274/dir.2026.263984. Online ahead of print.

ABSTRACT

PURPOSE: To evaluate the real-world multimetric performance of four commercially available computed tomography (CT)-based artificial intelligence (AI) solutions for acute intracranial hemorrhage (AIH).

METHODS: Patients who underwent non-contrast brain CT for suspected AIH in our emergency room between February and March 2024 were screened. After applying the inclusion and exclusion criteria, 436 CT scans were included in the final analysis. Three neuroradiologists established the ground truth for AIH and hemorrhage volume. For detection performance, the area under the receiver operating characteristic curve (AUROC), area under the precision-recall curve (AUPRC), and Brier score were calculated based on the available probability score, whereas sensitivity, specificity, precision, and F1 score were calculated based on binary classification. Bland-Altman analysis was performed to assess volumetric agreement for AIH between each algorithm’s calculations and the neuroradiologists’ measurements.

RESULTS: A total of 436 patients (mean age, 62 years ± 20; male patients, 209) were enrolled. The AUROC (0.96 to 0.99) and sensitivity (0.85 to 0.92) were high across all solutions, with no statistically significant differences in pairwise comparisons (P > 0.05). However, solution B demonstrated the highest AUPRC [0.98, 95% confidence interval (CI): 0.94, 1.00] and the lowest Brier score [0.02 (95% CI: 0.02, 0.03)]. In binary performance, both solutions B and D exhibited significantly higher specificity (1.00 and 0.99), precision (0.90 to 0.98), and F1 score (0.87 to 0.94) than the other solutions (P < 0.05). For volumetric agreement of AIH, solution D showed the lowest mean difference [-0.87 mm³ (95% CI: -1.47, -0.27)] and the narrowest limits of agreement (-13.4 to 11.6) relative to the neuroradiologists’ measurements.

CONCLUSION: In a real-world emergency setting, all four commercially available CT-based AI solutions for AIH demonstrated uniformly excellent performance; however, meaningful differences emerged in confirmatory performance and volumetric agreement. These distinct, algorithm-specific trade-offs provide practical guidance for selecting and integrating appropriate AI solutions to improve AIH diagnosis and management workflows.

CLINICAL SIGNIFICANCE: The algorithm-specific performance trade-offs identified in this study suggest that no single AI solution is universally optimal; solutions with superior confirmatory performance may reduce unnecessary notifications in high-volume emergency settings, whereas those with more consistent volumetric agreement may better support treatment planning and longitudinal monitoring. A structured, multimetric evaluation aligned with institutional priorities is essential for evidence-based AI procurement in acute stroke imaging.

PMID:42464524 | DOI:10.4274/dir.2026.263984

Arthritis Rheumatol. 2026 Jul 16. doi: 10.1002/art.70277. Online ahead of print.

ABSTRACT

OBJECTIVE: To characterize the long-term clinical course of children with hematologic non-criteria manifestations and persistent antiphospholipid antibodies (aPL), and to identify predictors of progression to antiphospholipid syndrome (APS) and/or systemic lupus erythematosus (SLE).

METHODS: We conducted a prospective cohort study of children (<18 years) with persistent aPL positivity and hematologic involvement (thrombocytopenia, autoimmune hemolytic anemia [AIHA], or Evans syndrome) followed at a tertiary pediatric rheumatology center between 1995 and 2024, with follow-up extending into adulthood. Progression to clinically classifiable APS and/or SLE was the primary endpoint. Kaplan-Meier and Cox proportional hazards models evaluated predictors at presentation and in complementary time-dependent analyses.

RESULTS: Among 42 enrolled children, 40 were evaluable, of whom 11 (27.5%) progressed to APS and/or SLE. Evans syndrome at presentation was associated with the highest hazard of progression compared with isolated thrombocytopenia (HR 6.21, 95% CI 1.46-26.41). In time-dependent analyses, Evans syndrome emerging during follow-up remained associated with progression. Isolated thrombocytopenia showed the lowest risk, whereas AIHA represented an intermediate state that did not independently predict progression. Lupus anticoagulant was nearly universal, and broader high-risk aPL profiles were more common among progressors but were not statistically significant.

CONCLUSION: In children with persistent aPL positivity, Evans syndrome was the hematologic phenotype most strongly associated with progression to APS and/or SLE, whereas isolated thrombocytopenia followed a largely indolent course. Evolving hematologic phenotypes may improve risk stratification and inform long-term monitoring strategies within the APS-SLE spectrum.

PMID:42463986 | DOI:10.1002/art.70277

Ophthalmol Ther. 2026 Jul 16. doi: 10.1007/s40123-026-01435-9. Online ahead of print.

ABSTRACT

INTRODUCTION: This prospective randomized controlled trial aims to evaluate the effectiveness and safety of a 180° nuclear flip technique in phacoemulsification cataract surgery, comparing it with the traditional endocapsular approach for cataracts of Emery-Little grade III and below.

METHODS: A total of 142 patients were randomly assigned to either the 180° nuclear flip group (n = 71) or the conventional endocapsular phacoemulsification group (n = 71). The primary outcomes measured were total phacoemulsification time (TPT) and effective phacoemulsification time (EPT). Secondary outcomes were the incidence of postoperative corneal endothelial cell loss (ECL) at 7 and 28 days, as well as intraoperative complications including posterior capsule rupture (PCR).

RESULTS: The mean TPT was substantially shorter in the flip group (43.75 ± 17.16 s) compared to the conventional group (58.45 ± 22.27 s) (P < 0.0001). Similarly, the mean EPT was also significantly reduced in the flip group (11.08 ± 5.25 s vs. 14.87 ± 8.54 s, P = 0.0046). There were no PCR cases in the flip group, whereas there was one case (1.4%) in the traditional group. At 28 days postoperatively, the mean ECL rate of the flip group (3.7%) was lower than that of the conventional group (4.9%), although this difference did not reach statistical significance.

CONCLUSION: The 180° nuclear flip technique is a safe, efficient, and effective method for managing cataracts of grade III hardness and below. It may help reduce the risk of complications, improves intraoperative stability by creating a more spacious operating field, and significantly reduces phacoemulsification time. Video available for this article.

TRIAL REGISTRATION: chictr.org.cn identifier, ChiCTR2500105241.

PMID:42463970 | DOI:10.1007/s40123-026-01435-9

Npj Ment Health Res. 2026 Jul 16;5(1):35. doi: 10.1038/s44184-026-00231-4.

ABSTRACT

The causal role of established risk factors for premenstrual disorders (PMDs) remains unclear. We used Mendelian randomization (MR) to assess causality for eight known-risk factors identified through a literature review. Summary statistics for these risk factors were from genome-wide association studies (GWAS) with sample size ranging from 129,017 to 1.2 million, and for PMDs from a GWAS of 72,297 participants. Findings were validated using one-sample MR in LifeGene cohort (n = 5674-5937). In two-sample MR, genetic liability to smoking initiation (OR = 1.25 (1.10-1.43)), earlier menarche (OR = 0.94 (0.89-0.98) per year), and higher BMI (OR = 1.19 (1.05-1.34) per kg/m²) were associated with PMD risk. No causal association was indicated for anemia, childhood abuse, childhood asthma, diabetes, and endometriosis. In one-sample MR, point estimates for BMI (OR = 1.10 (0.88-1.38) per kg/m²) and earlier menarche (OR = 0.98 (0.83-1.15) per year) were directionally consistent with the two-sample MR findings, but the confidence intervals included null effects. However, a null association was observed for smoking (OR = 0.94 (0.77-1.16)). The two-sample MR supports causal role of earlier menarche, higher BMI, and smoking in risk of PMDs. The lack of replication in one-sample MR highlights the need for triangulating evidence from future well-powered and methodologically comparable studies to strengthen these findings.

PMID:42463960 | DOI:10.1038/s44184-026-00231-4

Heredity (Edinb). 2026 Jul 16. doi: 10.1038/s41437-026-00861-6. Online ahead of print.

ABSTRACT

A Bayesian hybrid inference method is developed which infers hybrids and backcrosses across two generations using sampled genomes from two populations. The method improves on that of Chakraborty and Rannala (2023) by accounting for uncertainty of population haplotype frequencies and correctly marginalizing over haplotypes while still modeling linkage and recombination across the genome. In analyses of simulated data the new method produced posterior probabilities nearly identical to the method of Chakraborty and Rannala (2023) when sample sizes were large. For small sample sizes, posterior probabilities produced by the new method tended to be lower as expected since it accounts for additional uncertainties of population haplotype frequencies. Statistical performance of the new method as measured by the ROC (Receiver Operating Characteristic) curve appears equivalent to that of Chakraborty and Rannala (2023). The new method is applied to three recently published datasets for populations of kiwifruit (genus Actinidia), plateau fence lizard (Sceloporus tristichus) and puma (Puma concolor).

PMID:42463958 | DOI:10.1038/s41437-026-00861-6

Arch Gynecol Obstet. 2026 Jul 16. doi: 10.1007/s00404-026-08491-3. Online ahead of print.

ABSTRACT

OBJECTIVE: Poor responders pose a significant challenge in fertility treatment, leading to decreased oocyte quality and fertilization rates. Assisted oocyte activation (AOA) has emerged as a method to improve fertilization rates. This study aims to evaluate the effect of AOA on fertilization, pregnancy, and live birth rates in patients with diminished ovarian reserve.

MATERIALS AND METHODS: This prospective non-randomized comparative study included a cohort of infertility patients with diminished ovarian reserve, divided into three groups: the control group receiving standard treatment (Group I/Conventional ICSI), the electrical activation group undergoing piezoelectric stimulation (Group II/ICSI + Piezoelectric), and the chemical activation group treated with calcium ionophore (Group III/ICSI + Calcium Ionophore). Each group consisted of 50 patients. The effects of electrical and chemical activation applied after ICSI on fertilization, pregnancy, and live birth rates were evaluated.

RESULTS: There were no statistically significant differences among the groups in hormone levels (FSH, LH, E2, PRL, and AMH), number of oocytes, or number of MII oocytes. Fertilization rates were significantly higher in the piezoelectric group compared to the control group (p = 0.007). Although the fertilization rate in the calcium ionophore group was higher than that in the control group, this difference did not reach statistical significance (p = 1.000). There was no statistically significant difference in fertilization rates between the piezoelectric and calcium ionophore groups (p = 0.071). Regarding pregnancy rates, the highest implantation rate was observed in the calcium ionophore group (37%), but this difference does not reach statistical significance (p = 0.224). No significant differences were observed among the groups in embryo quality, clinical pregnancy, ongoing pregnancy, and live birth rates.

CONCLUSION: In patients classified as diminished ovarian reserve, artificial oocyte activation (AOA) was associated with higher fertilization rates for increasing fertilization rates, potentially resulting in a greater number of fertilized oocytes and transferable embryos. However, this apparent benefit does not translate into improved biochemical pregnancy outcomes. Moreover, no significant differences were observed between groups in terms of embryo quality, clinical pregnancy, ongoing pregnancy, and live birth rates. These findings suggest that while AOA may enhance early laboratory outcomes, its impact on clinically meaningful reproductive endpoints remains limited. Therefore, further adequately powered randomized studies are required to clarify the efficacy and safety of AOA.

PMID:42463955 | DOI:10.1007/s00404-026-08491-3