Category: Statistics

Int Urol Nephrol. 2026 Jul 10. doi: 10.1007/s11255-026-05235-9. Online ahead of print.

ABSTRACT

PURPOSE: This study aimed to characterize ferroptosis heterogeneity within the tumor microenvironment (TME) of clear cell renal cell carcinoma (ccRCC) and investigate its impact on immune remodeling and clinical prognosis.

METHODS: Single-cell transcriptomic analysis was performed using the GSE159115 dataset to classify cell phenotypes. Functional enrichment, immune infiltration, and pathway analyses (GSEA) were conducted. Validation utilized the GSE312695 and TCGA-KIRC cohorts.

RESULTS: ccRCC tissues were enriched with ferroptosis-resistant cells, whereas normal tissues contained ferroptosis-sensitive cells. Eight core genes regulating ferroptosis susceptibility were identified. Resistant cells established an immunosuppressive “immune desert” TME, with significant suppression of T-cell and macrophage pathways. The ferroptosis resistance signature demonstrated generalizability across cohorts, and medium-high resistance scores showed a trend toward poorer survival in specific subgroups, although overall survival differences did not reach statistical significance.

CONCLUSION: Ferroptosis heterogeneity contributes to ccRCC progression by shaping an immunosuppressive TME. The identified molecular features offer potential targets for therapy and highlight the complexity of utilizing ferroptosis signatures for prognostic assessment in ccRCC.

PMID:42430097 | DOI:10.1007/s11255-026-05235-9

Int Urol Nephrol. 2026 Jul 10. doi: 10.1007/s11255-026-05267-1. Online ahead of print.

ABSTRACT

OBJECTIVES: To assess whether simple quantitative multiparametric magnetic resonance imaging (mpMRI) measurements add diagnostic value to Vesical Imaging-Reporting and Data System (VI-RADS) scores for preoperative identification of muscle-invasive bladder cancer (MIBC).

METHODS: Tumor diameter, tumor-wall contact length, and VI-RADS scores were evaluated. The primary outcome was pathological MIBC. Diagnostic performance was assessed using receiver operating characteristic analysis, logistic regression, bootstrap internal validation, reclassification indices, calibration, and decision curve analysis.

RESULTS: The combined model including VI-RADS score (overall), average tumor diameter, and average tumor-wall contact length achieved an AUC of 0.808 (95% CI 0.739-0.876), compared with 0.769 (95% CI 0.702-0.836) for VI-RADS alone (DeLong P = 0.023). Continuous net reclassification improvement was 0.370 (95% CI 0.046-0.734), and integrated discrimination improvement was 0.034 (95% CI 0.003-0.116). Decision curve analysis suggested a modest gain in net benefit across threshold probabilities of 0.20-0.80.

CONCLUSION: Quantitative mpMRI measurements provided a modest, statistically significant but clinically limited incremental value beyond VI-RADS for identifying MIBC, although VI-RADS remained the main predictor.

PMID:42430096 | DOI:10.1007/s11255-026-05267-1

Behav Genet. 2026 Jul 10. doi: 10.1007/s10519-026-10276-y. Online ahead of print.

ABSTRACT

Caffeine intake may be influenced by both genetic and environmental factors. This study aimed to examine the genetic contribution to variation in coffee and tea drinking, as well as total caffeine intake. A total of 1,106 Korean twins, comprising 456 monozygotic and 97 dizygotic twin pairs aged 30 years or older, from the Healthy Twin Study were included. Structural equation models were used to assess heritability estimates and their 95% confidence intervals (CIs). Heritability (95% CI) was estimated at 0.29 (0.21, 0.37) for coffee drinking, 0.11 (0.02, 0.20) for tea drinking, and 0.27 (0.16, 0.38) for total caffeine intake, with the remaining variance in each trait attributed to unique environmental factors. The unique environmental factors contributed more substantially to coffee drinking than genetic factors during early adulthood, while the genetic contribution to tea drinking remained consistently low across all ages. In conclusion, coffee drinking, tea drinking, and total caffeine intake were partly heritable, with unique environmental factors playing a predominant role.

PMID:42430071 | DOI:10.1007/s10519-026-10276-y

Lasers Med Sci. 2026 Jul 10;41(1):145. doi: 10.1007/s10103-026-04946-w.

ABSTRACT

Fractional microneedle radiofrequency (FMR) has been proven effective and safe for acne scar and skin rejuvenation, but the treatment outcomes vary across different FMR devices. The face of each participant was randomly assigned as treatment side (treated with the Peninsula Timerevert Needle) and control side (treated with the EndyMed) along the midline. Outcome measures include melanin index (MI), erythema index (EI), stratum corneum hydration (SCH), sebum and dermal density on all facial sites. The treatment duration, participant’s satisfaction score and physician’s global assessment (PGA) score, pain score, bleeding score, erythema score and other side effects were evaluated. A total of 20 participants completed the entire course. The participant’s satisfaction score and PGA score increased progressively over time. Compared with the control side, the treatment side exhibited a shorter treatment time and lower pain score, but higher bleeding score. Dermal density increased gradually following FMR treatment and was statistically significant higher at 3 months than that at other follow-up time points. There were no statistically significant differences between the treatment and control sides in participant’s satisfaction score, PGA score, erythema score, erythema duration and edema duration, MI, EI, SCH, sebum and dermal density at the forehead, cheek and chin of at any follow-up time point. FMR is effective and safe for skin photoaging and acne scar. Peninsula Timerevert Needle ^TM offers the advantages of less pain and shorter treatment duration comparing with EndyMed, but is associated with a higher incidence of bleeding.

PMID:42430070 | DOI:10.1007/s10103-026-04946-w

Endocrine. 2026 Jul 10;91(1):221. doi: 10.1007/s12020-026-04706-4.

ABSTRACT

OBJECTIVE: Cardiovascular diseases (CVD) are the most common cause of death in the world. A number of scoring systems have been proposed to predict CVD risk. In this study, we aimed to assess the cardiovascular risk scores of transgender men receiving gender-affirming hormone therapy (GAHT).

METHODS: A total of 73 participants were included in this cross-sectional study: 43 transgender men, 15 cisgender men, and 15 cisgender women. For each participant, sociodemographic data were collected, glucose, lipid profiles and total testosterone levels were measured and the atherogenic index of plasma (AIP) and visceral adiposity index (VAI) were calculated.

RESULTS: The mean age of transgender men was 29.1 ±5.7. The neck circumference (NC), waist-to-hip ratio (WHR) and Waist-to-Height Ratio (WtHR) of transgender men was statistically higher than that of cis-women (p < 0.001, for all). Also, AIP was significantly higher in transgender men compared to cis- women (p = 0.003).

CONCLUSION: In conclusion, transgender men receiving GAHT exhibited differences in several cardiometabolic and anthropometric markers compared with cisgender women, with a profile more closely resembling that of cisgender men. These findings should be interpreted as descriptive differences rather than evidence of increased cardiovascular risk, particularly in the context of a cross-sectional design. The observed reduction in HDL cholesterol may be of clinical interest. Further longitudinal studies are warranted to better elucidate the long-term cardiometabolic effects of GAHT.

PMID:42430065 | DOI:10.1007/s12020-026-04706-4

Invest New Drugs. 2026 Jul 10. doi: 10.1007/s10637-026-01630-2. Online ahead of print.

ABSTRACT

Lazertinib is a third-generation, brain-penetrant, mutant-selective EGFR tyrosine kinase inhibitor approved for first-line treatment of EGFR-mutated non-small cell lung cancer, including in combination with amivantamab. Post-market safety surveillance is important given its recent approval and evolving real-world use. All FAERS reports with lazertinib as the primary suspect drug were extracted. Proportional Reporting Ratios (PRR), Reporting Odds Ratios (ROR), and chi-squared statistics were calculated for each adverse event. Disproportionality signals were defined by PRR ≥ 2, chi-squared ≥ 3.841, and a minimum of 3 reports. A total of 141 lazertinib reports were identified in the FAERS database. Twenty-six adverse events met all signal detection criteria. The strongest signals were observed for paronychia (PRR 132.90, n = 3), dermatitis acneiform (PRR 118.59, n = 4), peripheral sensory neuropathy (PRR 91.97, n = 3), and peripheral neuropathy (PRR 50.09, n = 28). Dermatologic and neurologic adverse events predominated, consistent with the mechanism of EGFR inhibition. FAERS disproportionality analysis identifies a signal profile for lazertinib dominated by EGFR inhibitor-class dermatologic and neurologic toxicities, alongside an infusion-related reaction signal reflecting combination use with amivantamab. The modest report volume warrants cautious interpretation; however, the signal patterns are mechanistically coherent and consistent with the known toxicity profile of third-generation EGFR TKIs.

PMID:42430026 | DOI:10.1007/s10637-026-01630-2

Mol Biol Rep. 2026 Jul 10;53(1):1132. doi: 10.1007/s11033-026-12338-0.

ABSTRACT

OBJECTIVE: Integrin αVβ3 has been implicated in oocyte membrane organization and sperm-oocyte interaction. This study investigated the effects of vitrification on post-warming survival and on the surface expression of integrin αV and β3 subunits in mouse oocytes at the germinal vesicle (GV) and metaphase II (MII) stages.

MATERIALS AND METHODS: A total of 400 oocytes were collected from NMRI mice and allocated into four equal groups: non-vitrified GV, vitrified GV, non-vitrified MII, and vitrified MII (n = 100 per group). Vitrification was performed using the Cryotop method, followed by one month of storage in liquid nitrogen at – 196 °C. Post-warming survival was assessed morphologically. Integrin αV and β3 expression was evaluated at the protein level by immunocytochemistry and at the transcript level by quantitative real-time reverse-transcription PCR (RT-qPCR).

RESULTS: Vitrification did not significantly affect post-warming survival rates in GV or MII oocytes compared with their non-vitrified counterparts (90% vs. 88%, P > 0.05). Immunocytochemical analysis demonstrated that both αV and β3 surface protein expression was significantly higher in MII oocytes than in GV oocytes, irrespective of vitrification status. Vitrification significantly reduced αV and β3 protein expression in MII oocytes compared with non-vitrified MII oocytes (P < 0.05 and P < 0.001, respectively), whereas reductions in GV oocytes were not statistically significant (P > 0.05). Quantitative RT-PCR broadly corroborated these findings: non-vitrified MII oocytes exhibited the highest transcript levels for both subunits, and β3 mRNA was significantly decreased in vitrified MII oocytes (P < 0.05). Although αV transcript levels showed a downward trend following vitrification, these reductions did not reach statistical significance in either stage (P > 0.05).

CONCLUSION: Despite preserving post-warming morphological survival, vitrification induced significant alterations in αV and β3 integrin expression in a maturation stage-dependent manner, with MII oocytes being disproportionately affected. These findings suggest that molecular analysis of membrane-associated proteins may provide information complementary to morphological criteria when assessing oocyte quality following cryopreservation.

PMID:42430017 | DOI:10.1007/s11033-026-12338-0

Lasers Med Sci. 2026 Jul 10;41(1):141. doi: 10.1007/s10103-026-04915-3.

ABSTRACT

The purpose of this study was to compare the effectiveness of Low-Level Laser Acupuncture with Dry Needling along with Routine Physical Therapy on clinical and functional outcomes in patients with Chronic Cervical Myofascial Pain Syndrome. An Assessor-blind Randomized Controlled trial was conducted at the Physical Therapy department of Rawal General & Dental Hospital, Pakistan. The study duration was June 2023 to November 2024. A non-probability convenience sampling technique was employed to produce a study sample of 100 individuals with Chronic Cervical Myofascial Pain Syndrome. The 100 eligible participants, with a mean age of 34 ± 7.21 years, were randomly allocated into two equal groups (n = 50 per group). Group A received Low-Level Laser Acupuncture and Routine Physical Therapy, while Group B underwent Dry Needling and Routine Physical Therapy. The outcomes of the study were pain intensity, neck disability, cervical range of motion, and health-related quality of life measured by the Numeric Pain Rating Scale, Neck Disability Index, Goniometer, and SF-36 health survey questionnaire, respectively. The outcome measures were evaluated at three temporal points: the pre, mid, and post-treatment sessions. Each participant received a total of 18 treatment sessions. The IBM SPSS Statistics version 26.0 was used to analyze and interpret the results. The Mann-Whitney U test, Friedman test, and subsequent Wilcoxon signed-rank post hoc analyses with Bonferroni adjustment demonstrated statistically significant differences (p < 0.05 in all cases), both intergroup and intragroup over time. The Low-Level Laser Acupuncture and Dry Needling both proved to be efficient adjunct therapies to routine physical therapy for Chronic Cervical Myofascial Pain Syndrome for different durations of improvement.

PMID:42430011 | DOI:10.1007/s10103-026-04915-3

Mol Biol Rep. 2026 Jul 10;53(1):1139. doi: 10.1007/s11033-026-12328-2.

ABSTRACT

OBJECTIVE: Heart failure with reduced ejection fraction (HFrEF) remains a major global health burden characterized by progressive cardiac dysfunction and high mortality. Emerging evidence suggests that epigenetic modifications, especially DNA methylation of antioxidant-related genes, may influence the molecular mechanisms underlying heart failure. This study aimed to investigate the methylation status of the glutathione peroxidase 4 (GPX4) promoter region in patients with HFrEF and to explore its associations with clinical and biochemical indicators.

METHODS: A total of 125 patients with HFrEF (LVEF < 50%) and 350 healthy controls were enrolled. Peripheral blood genomic DNA was extracted, and CpG methylation levels within the GPX4 promoter (FA3 and FA20 regions) were quantified using matrix-assisted laser desorption/ionization-time-of-flight mass spectrometry (MALDI-TOF MS). Statistical analyses were performed using t-tests, Mann-Whitney U tests, and χ² tests. Restricted cubic spline (RCS) models were then applied to assess potential nonlinear dose-response relationships between methylation levels and clinical variables.

RESULTS: Methylation at GPX4_FA3_CpG_5 was significantly higher in HFrEF patients than in healthy controls (P = 0.019). Stratified analysis by NYHA class revealed increased methylation at GPX4_FA20_CpG_6 in patients with class I/II heart failure compared with those with class III/IV disease (P = 0.017). RCS modeling identified nonlinear U-shaped or multiphasic associations between GPX4_FA3_CpG_5 methylation and several clinical indicators, including total bile acid (TBA), fibrinogen (FG), fibrin degradation products (FDP), and eosinophil percentage (EO%). No significant associations were detected between GPX4 methylation and blood lipid or routine hematologic parameters.

CONCLUSION: In HFrEF patients, GPX4 promoter methylation is closely associated with clinical and biochemical alterations. Site-specific changes suggest that dysregulation of the GPX4-mediated antioxidant network and ferroptosis-related pathways may contribute to cardiac dysfunction. The nonlinear dose-response relationships with hepatic and coagulation markers indicate complex metabolic interplay. These findings support GPX4 promoter methylation as a potential epigenetic marker for HFrEF.

PMID:42430008 | DOI:10.1007/s11033-026-12328-2

Lasers Med Sci. 2026 Jul 10;41(1):144. doi: 10.1007/s10103-026-04937-x.

ABSTRACT

The use of lasers and light devices in dermatology has significantly increased in recent years due to their ease of treatment, predictable clinical efficacy, and minimal side effects. Numerous studies have explored the use of lasers in acne treatment, including Q-Switched Nd: YAG 1064 nm laser, pulsed dye laser (PDL), intense pulsed light (IPL), diode lasers, and laser-based photodynamic therapy. This study aimed to compare the efficacy and side effects of Q-Switched Nd: YAG 1064 nm laser, PDL, and IPL in the treatment of acne. This pilot study was a three-arm randomized controlled trial involving 36 patients with moderate to severe inflammatory acne. Participants were randomly assigned to one of three groups. Group 1 received three PDL laser treatments at two-week intervals, Group 2 received three IPL treatments at two-week intervals, and Group 3 received three sessions of Q-Switched Nd: YAG 1064 nm laser treatments at two-week intervals. A total of 36 patients were randomly assigned to three groups (PDL, IPL, and Q-Switched Nd: YAG 1064 nm laser) to evaluate the efficacy and safety of each treatment for inflammatory acne. No significant differences were observed in acne lesion counts or severity scores between the groups at any treatment session (P-values ranging from 0.06 to 0.92). Lesion counts and severity decreased significantly within each group over the course of the study. Acne-related disability, measured using the Cardiff Acne Disability Index (CADI), decreased significantly from baseline to two weeks after the third treatment session in all groups, indicating improved quality of life. No statistically significant difference was observed between the groups (P = 0.45). Adverse effects were minimal, with mild erythema reported by one participant in the PDL group, and the Nd: YAG group reported less pain during treatment compared to the others. All three treatment modalities were associated with improvements in acne lesion count, lesion severity, and CADI scores. The reduction in CADI scores indicated reduced acne-related disability and improved quality of life. However, no statistically significant differences were observed between the groups. Therefore, PDL, IPL, and Nd: YAG may be considered promising short-term treatment options for inflammatory acne.

PMID:42430005 | DOI:10.1007/s10103-026-04937-x