Tag: pubmed

Nat Med. 2026 May 10. doi: 10.1038/s41591-026-04408-4. Online ahead of print.

ABSTRACT

MicroRNA-132 (miR-132) is a central regulator of adverse cardiac remodeling. Here we evaluated CDR132L, a synthetic antisense oligonucleotide miR-132 inhibitor, in a multinational, randomized, double-blind, placebo-controlled phase 2 trial (HF-REVERT) in patients with recent myocardial infarction (MI) and left ventricular (LV) systolic dysfunction. Within 3-14 days after MI, 294 patients were randomized to receive CDR132L 5 mg kg^-1, CDR132L 10 mg kg^-1 or placebo as three intravenous doses at 4-week intervals plus guideline-directed therapy. In total, 280 patients (245 men and 35 women) who received at least one dose of the study drug were included in the modified intention-to-treat population. CDR132L was well tolerated, with no hepatic, renal, hematologic or cardiac toxicity signals. The primary endpoint-the percentage change in LV end-systolic volume index at 6 months-improved in all groups but did not differ significantly between the CDR132L groups (5 mg kg^-1 and 10 mg kg^-1) and the placebo group. Secondary endpoints, including LV ejection fraction, global longitudinal strain and N-terminal pro B-type natriuretic peptide, were also not significantly different between the CDR132L and placebo groups. Prespecified exploratory analyses suggested potential benefits of CDR132L treatment in patients with advanced adverse remodeling at baseline, supporting further evaluation of CDR132L, including in chronic heart failure conditions. ClinicalTrials.gov: NCT05350969 .

PMID:42108271 | DOI:10.1038/s41591-026-04408-4

Sci Rep. 2026 May 10. doi: 10.1038/s41598-026-51415-z. Online ahead of print.

ABSTRACT

Cholera is highly climate sensitive, however previous attempts to model its future under climate change have been limited to statistical analyses. Mechanistic models are an essential addition because they permit a deeper understanding of the complex feedback loops involved in infectious disease transmission, allowing for better modelling of potential scenarios such as interventions or changes in pathogen dynamics. We compare four mathematical models with differing assumptions of climate sensitivity and fit them to a cholera dataset from Kolkata, India using MCMC. We then use bias-corrected climate projections of temperature and rainfall from 10 independent global climate models to produce climate-based cholera projections for the period 2080-2099. Using both temperature and rainfall as inputs, the best performing model recreates seasonal patterns highly effectively. Future projections suggest an average increase in cholera cases ranging from 81% – 150% due to climate change by 2080-2099 with earlier peaks in the infection cycle likely due to heightened transmission rates earlier in the year. Sensitivity analysis reveals that uncertainties in parameters related to the contact rate and water dynamics have the greatest impact on model projections, suggesting that these factors are critical for refining future predictions. While our mechanistic model demonstrates the potential to project cholera dynamics under future climate scenarios, projections remain sensitive to key knowledge gaps including epidemiological parameters and effects of temperature on bacterial growth. Addressing these limitations through improved environmental observations and more detailed process representation will be essential for refining future climate-cholera projections and informing long-term control strategies.

PMID:42108242 | DOI:10.1038/s41598-026-51415-z

J Clin Exp Neuropsychol. 2026 May 10:1-9. doi: 10.1080/13803395.2026.2673080. Online ahead of print.

ABSTRACT

INTRODUCTION: Cognitive estimation is a component of executive functions, involving judgment, reasoning, often impaired in neurological disorders. This study aimed to develop the Bilişsel Tahmin Testi (BiTAHT) for the Turkish population and to evaluate its reliability and validity in patients with Multiple Sclerosis (pwMS).

METHOD: The study was conducted in four sequential phases. In the first phase, 56 preliminary estimation items were generated based on a review of existing Cognitive Estimation Tests and expert feedback. In the second phase, the items were evaluated for clarity, linguistic appropriateness, and feasibility through pilot testing with a small sample. In the third phase, BiTAHT was administered to 1,112 healthy participants, and statistical analyses including percentile calculation and item-level outlier removal were used to refine the test and develop two parallel forms (BiTAHT-A and BiTAHT-B). In the final phase, reliability and validity were assessed by administering BiTAHT to 54 pwMS and 80 controls. The final version comprised six estimation categories: quantity, weight, length, duration, area, and equivalent.

RESULTS: Each parallel form contained 13 estimation items. PwMS performed significantly worse than healthy controls in the quantity, weight, length, and equivalent categories, but not in duration or area. In the development sample, BiTAHT scores varied by age, gender, and education with low effect sizes, while no associations were found in validation groups (54 pwMS, 80 controls) (p > .05). İnternal consistency was moderate when the two forms were combined.

CONCLUSIONS: BiTAHT may be used to assess cognitive estimation abilities in Turkish adults and support future research on cultural validity. Although differences were observed between healthy controls and pwMS, these should not be interpreted as executive dysfunction. Future studies should evaluate test – retest reliability, expand validity evidence, and examine its utility in other neurological populations.

PMID:42108237 | DOI:10.1080/13803395.2026.2673080

Pharm Stat. 2026 May-Jun 6;25(3):e70097. doi: 10.1002/pst.70097.

ABSTRACT

Analysis of genomics data for predicting disease outcomes is a fast-growing field in medical research. There often exist categorical, specifically, ordinal outcomes that need to be predicted based on genomic profiles. This has led to recent development of some high-dimensional ordinal classification methods that can address the large dimensionality of the genomic covariate set. These high-dimensional ordinal models tend to vary widely in their performance depending on the data they are applied to and the evaluation criteria used. In this article, we outline an ensemble ordinal classifier that integrates different ordinal modeling approaches through bootstrap-based model evaluation, multi-metric performance assessment, and rank aggregation to produce a final prediction that can alleviate the uncertainty of relying on a single model. Through multiple simulated studies and real genomic data analyses, we show that the ensemble method consistently ranks among the top-performing models. These findings underscore the potential of ensemble learning to improve the robustness and predictive accuracy of high-dimensional ordinal classification in genomic research.

PMID:42108236 | DOI:10.1002/pst.70097

Med Phys. 2026 May;53(5):e70473. doi: 10.1002/mp.70473.

ABSTRACT

BACKGROUND: Transperineal ultrasound (TPUS) is a valuable imaging tool for evaluating patients with a variety of pelvic floor disorders, including pelvic organ prolapse (POP). Currently, calculating measurements of anatomical structures and relationships as well as extracting the mid-sagittal (MS) plane of 2D and 3D ultrasound images are obtained manually, which is a time-consuming process and requires a reviewer with prior training in pelvic floor US interpretation. The need for manual analysis of ultrasound images has limited the broader adoption of TPUS for evaluating pelvic floor disorders in both research and clinical practice. An automated segmentation and plane extraction method would improve the ability to easily quantify pelvic anatomy relevant to pelvic floor disorders and improve the efficiency and reproducibility of POP diagnosis and treatment.

PURPOSE: To develop a fast, reproducible, and automated method of acquiring the MS plane, plane of minimal hiatal dimensions (PMHD), and segmentations of the pelvic floor organs from 3D TPUS images.

METHODS: Our method used a nnU-Net segmentation model to segment structures of interest in the 3D TPUS images. The model segmented the pubis symphysis (PS), urethra, bladder, rectum, rectal ampulla, and anorectal angle (ANA). The segmented output was then fed into a heuristics-based method to determine the PS and ANA to extract the MS plane and PMHD automatically. We used a dataset consisting of 161 3D TPUS images from 104 patients. 89 of the volumes were acquired in a resting state and 72 during the Valsalva maneuver. The segmentation and plane extraction algorithms were evaluated by comparing the results with manual segmentations and manual plane extraction methods using the dice similarity coefficients (DSC), mean absolute surface distance (MAD), and absolute angle difference (AAD), respectively. The Wilcoxon-signed rank statistical test was used with Bonferroni-correction to p < 0.01. Cohen effect size was used for comparing model results.

RESULTS: The nnU-Net segmentation model reported an average DSC(%) of 70.4%, 58.5%, 57.1%, 48.9%, 39.0%, and 19.8% for bladder, rectum, PS, urethra, ANA, and rectal ampulla respectively. The nnU-Net segmentation model achieved significantly higher DSC (p < 0.01) for the urethra and rectum than all other tested models. Across all metrics, the nnU-Net segmentation model achieved an average effect size of 0.3, 0.5, 0.7, and 0.8 compared to a 3D ResNet34 + U-Net, 3D U-Net, 2D U-Net, and Attention 3D U-Net model, respectively. The average AADs between the automatically calculated plane slices and manually estimated planes dataset for the MS plane and PMHD were 3.8° and 2.4°, respectively. The PS and ANA segmentation centroids were used to calculate the MS plane and PMHD and they had distance errors of 3.6 mm and 4.4 mm.

CONCLUSIONS: We developed an automated 3D segmentation and multiple plane extraction method of female pelvic floor 3D US images. Our method extracts the MS plane and PMHD from 3D US images. The proposed algorithm pipeline can improve the efficiency and reproducibility of TPUS analysis for pelvic floor disorder diagnosis and treatment.

PMID:42108227 | DOI:10.1002/mp.70473

Ter Arkh. 2026 May 2;98(4):226-230. doi: 10.26442/00403660.2026.04.203576.

ABSTRACT

AIM: To assess the circulating levels of IL-1 and its activity regulators, IL-1Ra and IL-1R2, in patients with acute decompensated heart failure (ADHF) depending on body mass index (BMI).

MATERIALS AND METHODS: The study included 159 patients hospitalized for ADHF. Depending on the BMI, the patients were assigned to 5 groups. The first group included 30 patients with healthy weight (BMI<25 kg/m²), the second – 50 overweight patients (25≤BMI<30 kg/m²), the third – 38 patients with class I obesity (30≤BMI<35 kg/m²), the fourth – 28 patients with class II obesity (35≤BMI<40 kg/m²), the fifth group – 13 patients with class III obesity (BMI≥40 kg/m²).

RESULTS: With increasing BMI, IL-1 levels increased, while IL-1R2 levels, on the contrary, decreased, but no statistically significant differences were found. IL-1Ra concentrations changed ambiguously and had U-shaped dependence. IL-1Ra levels were lower in overweight patients than in normal weight and obese groups. At the same time, the increase in obesity was accompanied by higher IL-1Ra levels. The highest IL-1Ra value was observed at a BMI≥40 kg/m².

CONCLUSION: In ADHF an increase in obesity is accompanied by an increase in the inhibition of IL-1 activity, which may be one of the mechanisms by which adipose tissue exerts a protective effect.

PMID:42107125 | DOI:10.26442/00403660.2026.04.203576

Ter Arkh. 2026 May 2;98(4):217-225. doi: 10.26442/00403660.2026.04.203575.

ABSTRACT

AIM: The study examined the composition of the gut microbiota (GM) in patients with urolithiasis compared to healthy volunteers, based on laboratory, instrumental, and gastroenterological quality of life questionnaire (Gastrointestinal Symptom Rating Scale – GSRS) results.

MATERIALS AND METHODS: The composition of GM was studied using fecal samples obtained from 35 patients with urolithiasis and 31 healthy volunteers using gas chromatography-mass spectrometry. The GSRS questionnaire was used to assess gastrointestinal symptoms. In the group of patients with urolithiasis, the body mass index, serum creatinine concentration (with calculation of glomerular filtration rate), and serum uric acid concentration were analyzed, as well as the density of urinary stones using multispiral computed tomography (MSCT) in Hounsfield units (HU).

RESULTS: Statistical analysis of the data revealed violations of the composition of the GM against the background of urolithiasis in comparison with healthy volunteers (control group): patients with urolithiasis had a statistically significant increase in the content of bacteria Corynebacterium spp., Peptostreptococcus anaerobius 18623, a decrease in the number of Clostridium propionicum (Anaerotignum propionicum), on average, 7 times, compared to the control group. When comparing the composition of the GM depending on the type of urinary stones, in the subgroup of patients with oxalate stones (n=18), an increase in the number of Clostridium perfringens was detected in the fecal samples, and in the subgroup of patients with uric acid stones (n=17), a decrease in the number of Prevotella bacteria was observed. In patients with urolithiasis, there was a negative correlation between the total GSRS score and the severity of dyspepsia syndrome, as well as the number of Propionibacterium spp. in the GM.

CONCLUSION: The composition of the GM in patients with urolithiasis was significantly different from that of the GM in healthy volunteers. Statistically significant differences in the composition of the GM were found in patients with uric acid and oxalate stones.

PMID:42107124 | DOI:10.26442/00403660.2026.04.203575

Ter Arkh. 2026 May 2;98(4):209-216. doi: 10.26442/00403660.2026.04.203574.

ABSTRACT

AIM: To identify functional features in patients with interstitial lung diseases (ILD), depending on disease phenotypes, using the forced oscillation technique.

MATERIALS AND METHODS: A single-center cross-sectional observational study was conducted on 68 patients with ILD (mean age 64 years, 70.6% women). The diagnoses were distributed as follows: idiopathic pulmonary fibrosis 17.7%, chronic hypersensitivity pneumonitis 44.1%, non-specific interstitial pneumonia 14.7%, unclassified ILD 23.5%. According to Tomographia Computata data, fibrotic changes were detected in 74.1% of patients. All patients underwent comprehensive pulmonary function testing, including spirometry, body plethysmography, measurement of diffusing capacity of the lungs, and oscillometry (forced oscillation technique).

RESULTS: The ΔX5 parameter was statistically significantly higher in patients with a fibrotic phenotype than in those without fibrosis [0.92 (0.06- 1.63) hPa×s/L vs 0.19 (-0.05-0.43) hPa×s/L; p=0.016]. Patients with fibrosis also had significantly lower for diffusing capacity of the lungs (45.5% vs 52% predicted; p=0.027) and CO diffusion capacity – Kco (73% vs 81.5% predicted; p=0.037) values. Independent predictors of the fibrotic phenotype were ΔX5 (odds ratio 6.386, 95% confidence interval 1.479-27.564; p=0.013) and Kco (odds ratio 0.929, 95% confidence interval 0.867-0.997; p=0.040). ROC analysis showed that the combination of ΔX5 and Kco parameters has high diagnostic value for detecting fibrosis (AUC 0.817; p<0.001).

CONCLUSION: The oscillometry parameter ΔX5 and the Kco index from diffusing capacity measurement are independent predictors of a fibrotic phenotype in patients with ILD. The combination of these functional parameters improves diagnostic capabilities for detecting fibrotic changes. The FOT method provides clinically important information in patients with ILD and restrictive impairment.

PMID:42107123 | DOI:10.26442/00403660.2026.04.203574

Chembiochem. 2026 May 14;27(9):e70368. doi: 10.1002/cbic.70368.

ABSTRACT

Duchenne Muscular Dystrophy (DMD) and Ehlers-Danlos Syndrome (EDS) are characterized by genetic instability due to DNA damage leading to loss of muscular function. Genetic impacts of these diseases were probed by extracting DNA from selected muscle tissues of either a mouse model of X chromosome-linked muscular dystrophy (mdx, DMD model) or a heterozygous col5a1 (+/-) mouse (EDS model). Complementary square wave voltammetry (SWV) and liquid chromatography-tandem mass spectrometry (LC-MS/MS) approaches were used to assess extracted DNA. SWV analysis was performed by immobilizing DNA layer-by-layer (LbL) on pyrolytic graphite (PG) electrodes before oxidation in the presence of Ru(bpy)₃ ²⁺. Changes in SWV peak currents (I_p) at ∼+1.05 V vs. SCE indicated significant DNA alterations in the genetically altered mouse tissues compared to wild type (WT) controls. Both mdx and heterozygous col5a1(+/-) samples exhibited statistically significant decreased I_p levels (p < 0.05) compared to WT DNA suggesting guanine content varied due to the genetic alterations, which was statistically more significant in leg muscle DNA. MS/MS validated and expanded on the SWV results. DNA base analysis showed increased oxidative damage alongside changes in undamaged base content in mdx mice. DNA from col5a1(+/-) leg muscles exhibited significant changes to undamaged base content, showcasing similar trends.

PMID:42107099 | DOI:10.1002/cbic.70368

J Psychosoc Oncol. 2026 May 10:1-10. doi: 10.1080/07347332.2026.2668705. Online ahead of print.

ABSTRACT

BACKGROUND: We adapted a previously-successful intervention, StoryListening, to a group setting for LGBTQ+ cancer survivors.

OBJECTIVE: Our goal was to assess the feasibility and acceptability of the QT (Queer/Trans) Cancer StoryListening Workshop.

METHODS: We conducted a single-arm pilot feasibility trial of QT Cancer StoryListening for LGBTQ+ cancer survivors in September, 2025. Feasibility was assessed by enrollment and questionnaire completion data. Acceptability was evaluated using self-report questionnaires with both closed-ended and open-ended items. We used a mixed methods analytic approach, including both descriptive statistics and deductive thematic content analysis.

RESULTS: Twelve individuals responded with interest in 5 wk of community outreach; 10 (83%) attended the workshop and 8 completed follow-up questionnaires (80%). Participants identified no emotional or logistical difficulty in participating and all identified value, particularly around the community aspect of the workshop. LGBTQ+ cancer survivors lack specifically-tailored support.

CONCLUSION: StoryListening is a brief, scalable intervention that is both feasible and acceptable to LGBTQ+ cancer survivors.

PMID:42107087 | DOI:10.1080/07347332.2026.2668705