Nevin Manimala

J Clin Psychopharmacol. 2025 Feb 14. doi: 10.1097/JCP.0000000000001964. Online ahead of print.

ABSTRACT

BACKGROUND: This randomized, double-blind, placebo-controlled trial (ClinicalTrials.gov identifer NCT04285515) evaluated efficacy and safety of lumateperone to treat major depressive episodes (MDEs) associated with major depressive disorder (MDD) or bipolar depression with mixed features.

PROCEDURES: Patients (18-75 years) with Diagnostic and Statistical Manual of Mental Disorders, 5th edition (DSM-5)-defined MDD with mixed features (n = 185) or bipolar disorder with mixed features (n = 200) and experiencing an MDE were randomized 1:1 to 6-week placebo (n = 195) or lumateperone 42 mg (n = 193). Primary and key secondary endpoints were change from baseline to day 43 in Montgomery-Åsberg Depression Rating Scale Total and Clinical Global Impression Scale-Severity (CGI-S) scores in 3 populations with combined MDD/bipolar depression, individual MDD, and individual bipolar depression. Safety included adverse events (AEs), extrapyramidal symptoms, and laboratory parameters.

RESULTS: Lumateperone met the primary endpoint, significantly improving Montgomery-Åsberg Depression Rating Scale total score at day 43 in populations with combined MDD/bipolar depression (least squares mean difference vs placebo [LSMD], -5.7; 95% confidence interval [CI], -7.60,-3.84; effect size [ES], -0.64; P < 0.0001), MDD (LSMD, -5.9; 95% CI, -8.61,-3.29; ES, -0.67; P < 0.0001), and bipolar depression (LSMD, -5.7; 95% CI, -8.29,-3.05; ES, -0.64; P < 0.0001). Lumateperone significantly improved CGI-S and Young Mania Rating Scale total scores at day 43 in these populations. Lumateperone was well-tolerated. Treatment-emergent AEs (≥5%, twice placebo) in the combined population were somnolence (placebo, 1.6%; lumateperone, 12.5%), dizziness (placebo, 2.1%; lumateperone, 12.0%), and nausea (placebo, 1.6%; lumateperone, 9.9%). There were no mania/hypomania treatment-emergent AEs with lumateperone and minimal extrapyramidal symptoms or metabolic risk.

CONCLUSIONS: Lumateperone 42 mg significantly improved depression symptoms and disease severity and was generally safe and well-tolerated in patients with MDD or bipolar depression with mixed features.

PMID:39946099 | DOI:10.1097/JCP.0000000000001964

Bioinformatics. 2025 Feb 13:btaf072. doi: 10.1093/bioinformatics/btaf072. Online ahead of print.

ABSTRACT

MOTIVATION: Copy number alterations are driving forces of tumour development and the emergence of intra-tumour heterogeneity. A comprehensive picture of these genomic aberrations is therefore essential for the development of personalised and precise cancer diagnostics and therapies. Single-cell sequencing offers the highest resolution for copy number profiling down to the level of individual cells. Recent high-throughput protocols allow for the processing of hundreds of cells through shallow whole-genome DNA sequencing. The resulting low read-depth data poses substantial statistical and computational challenges to the identification of copy number alterations.

RESULTS: We developed SCICoNE, a statistical model and MCMC algorithm tailored to single-cell copy number profiling from shallow whole-genome DNA sequencing data. SCICoNE reconstructs the history of copy number events in the tumour and uses these evolutionary relationships to identify the copy number profiles of the individual cells. We show the accuracy of this approach in evaluations on simulated data and demonstrate its practicability in applications to two breast cancer samples from different sequencing protocols.

AVAILABILITY: SCICoNE is available at https://github.com/cbg-ethz/SCICoNE.

SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.

PMID:39946094 | DOI:10.1093/bioinformatics/btaf072

Eur Arch Paediatr Dent. 2025 Feb 13. doi: 10.1007/s40368-025-01006-9. Online ahead of print.

ABSTRACT

PURPOSE: Molar-incisor hypomineralisation (MIH) impacts children’s oral health and quality of life, but research on the stomatognathic system of unilateral cases, remains limited. This study evaluated the effects of unilateral MIH on the stomatognathic system in children, focusing on postural and masticatory activities and occlusal force contacts.

METHODS: In this cross-sectional observational study, 28 children (mean age: 8.21 years) were divided into two groups: without MIH (CG) and with unilateral MIH (MIHG). Electromyography (EMG) evaluated the activity of masseter and temporalis muscles during various jaw postures and habitual chewing. Occlusal force contacts were measured using T-SCAN®. Comparisons were made between groups and sides. Statistical analysis employed the Shapiro-Wilk test, Wilcoxon signed-rank test, and paired t-test, with a significance level of 5%.

RESULTS: EMG data demonstrated increased muscle hyperactivity in MIHG compared to CG at rest for the left temporalis muscle on the contralateral side (p < .001), during left laterality for the right temporalis muscle on the ipsilateral side (p = 0.04), and habitual chewing of soft food for the left temporalis muscle on the contralateral side (p = 0.02). Greater voluntary contraction was observed on the unaffected side in MIHG for the temporalis muscle at rest (p = 0.01) and the masseter muscle during right laterality (p = 0.02). No significant differences were found in occlusal force measurements between groups or sides.

CONCLUSIONS: This study indicates that unilateral MIH is associated with increased muscle hyperactivity in the contralateral temporalis and masseter muscles, without significant differences in occlusal force.

PMID:39946081 | DOI:10.1007/s40368-025-01006-9

J Endocrinol Invest. 2025 Feb 13. doi: 10.1007/s40618-025-02550-3. Online ahead of print.

ABSTRACT

PURPOSE: To detect the expression of miR-27a-5p in differentiated thyroid cancer (DTC) and to explore its correlation with SREBP1 expression, DTC malignant progression, and TSH suppression therapy.

METHODS: The expression levels of SREBP1 and miR-27a-5p in DTC tissues (n = 75) were detected by qRT-PCR. The expression of miR-27a-5p and SREBP1 was statistically analyzed for correlation with patients’ postoperative TSH inhibition therapy. Dual luciferase reporter gene assay was performed to verify the target-regulatory relationship between miR-27a-5p and SREBP1. qRT-PCR and Western blots were performed to detect the effect of miR-27a-5p on the expression level of SREBP1. MTS, plate clone formation assay was performed to detect the effect of miR-27a-5p on the proliferative capacity of cells. Flow cytometry was performed to detect the effect of miR-27a-5p on cell cycle and apoptosis. Scratch assay and Transwell assay was performed to detect the effect of miR-27a-5p on cell migration invasion ability.

RESULTS: MiR-27a-5p expression was significantly downregulated in DTC cancer tissues and significantly negatively correlated with SREBP1 expression. It correlated with the outcome of postoperative TSH suppression therapy in DTC patients. The results of dual luciferase reporter gene assay showed that the 3′-UTR region of SREBP1 mRNA was the target site of action of miR-27a-5p. Overexpression of miR-27a-5p was associated with a significant reduction in cell proliferation, cell cycle arrest, increased apoptosis, and diminished cell invasive migration.

CONCLUSION: The miR-27a-5p expression level was negatively correlated with the progression of DTC, which may be inhibited by targeting SREBP1 and correlated with the outcome of TSH inhibitory therapy.

PMID:39946050 | DOI:10.1007/s40618-025-02550-3

Eur J Epidemiol. 2025 Feb 13. doi: 10.1007/s10654-024-01185-7. Online ahead of print.

ABSTRACT

Recent advancements in machine learning (ML) for analyzing heterogeneous treatment effects (HTE) are gaining prominence within the medical and epidemiological communities, offering potential breakthroughs in the realm of precision medicine by enabling the prediction of individual responses to treatments. This paper introduces the methodological frameworks used to study HTEs, particularly based on a single randomized controlled trial (RCT). We focus on methods to estimate conditional average treatment effect (CATE) for multiple covariates, aiming to predict individualized treatment effects. We explore a range of methodologies from basic frameworks like the T-learner, S-learner, and Causal Forest, to more advanced ones such as the DR-learner and R-learner, as well as cross-validation for CATE estimation to enhance statistical efficiency by estimating CATE for all RCT participants. We also provide a practical application of these approaches using the Preventing Overweight Using Novel Dietary Strategies (POUNDS Lost) trial, which compared the effects of high versus low-fat diet interventions on 2-year weight changes. We compared different sets of covariates for CATE estimation, showing that the DR- and R-learners are useful for the estimation of CATE in high-dimensional settings. This paper aims to explain the theoretical underpinnings and methodological nuances of ML-based HTE analysis without relying on technical jargon, making these concepts more accessible to the clinical and epidemiological research communities.

PMID:39946045 | DOI:10.1007/s10654-024-01185-7

Environ Sci Pollut Res Int. 2025 Feb 13. doi: 10.1007/s11356-025-36049-4. Online ahead of print.

ABSTRACT

Traditional drought indices, such as the Standardized Precipitation Index (SPI) and Standardized Runoff Index (SRI), often fail to capture the complexity of drought events, which involve multiple interacting variables. To address this gap, this study applies the Principle of Maximum Entropy (POME) copula to combine SPI and SRI into a Joint Deficit Index (JDI), offering a more complete assessment of hydrometeorological drought. We used machine learning models, including Random Forest (RF), Quantile Random Forest (QRF), Extreme Gradient Boosting (XGB), and Quantile Regression XGBoost (QXGB), to predict JDI, while also incorporating uncertainty analysis using the Uncertainty Estimation based on Local Errors and Clustering (UNEEC) method. This approach not only improves the accuracy of drought predictions but also quantifies the uncertainty of the models, enhancing reliability. Model performance, evaluated with R², RMSE, and MAE, showed XGB as the best performer, achieving R² = 0.93 and RMSE = 0.16. This integration of multivariate drought indices, machine learning, and uncertainty analysis provides a more robust tool for drought monitoring and water resource management in arid regions.

PMID:39946044 | DOI:10.1007/s11356-025-36049-4

J Interv Card Electrophysiol. 2025 Feb 13. doi: 10.1007/s10840-025-02008-9. Online ahead of print.

ABSTRACT

BACKGROUND: Pulmonary vein isolation (PVI) is a cornerstone of AF ablation. Posterior wall isolation (PWI) has become a frequently used adjunct to PVI. While there is data to suggest that PVI alone does not negatively impact left atrial function, the effect of PWI on left atrial mechanical function has not been definitively determined. Our aim was to determine if PVI plus PWI using a cryoballoon impacted left atrial mechanical function as measured by cardiac MRI.

METHODS: We studied 28 patients who underwent ablation for AF. Fourteen patients had PVI alone and 14 patients had PVI plus PWI. All patients had cardiac magnetic resonance (CMR) before and after ablation. The primary outcome was change in LA ejection fraction (LAEF) as measured by CMR.

RESULTS: There were no statistically significant differences in the average patient age, height, weight, type of AF, or frequency of concomitant diseases between groups. No statistically significant differences in LAEF, LA max volume, LA min volume, or LA stroke volume were identified between baseline and follow up CMRs for the PVI only group nor the PVI plus PWI group. When utilizing linear regression analysis to compare change in LAEF, LA max volume, LA min volume, and LA stroke volume before and after ablation between groups, no statistically significant differences were identified.

CONCLUSION: Cardiac MRI did not demonstrate a significant change in left atrial mechanical function as measured by left atrial ejection fraction after pulmonary vein isolation alone nor after PVI plus posterior wall isolation.

PMID:39946035 | DOI:10.1007/s10840-025-02008-9

Drugs. 2025 Feb 13. doi: 10.1007/s40265-025-02157-1. Online ahead of print.

ABSTRACT

BACKGROUND AND OBJECTIVE: Bimatoprost implant 10 µg (Durysta) is an intracameral biodegradable implant that releases bimatoprost to lower intraocular pressure (IOP). The purpose of this study was to prospectively collect effectiveness and safety data after administration of the implant in patients with open-angle glaucoma or ocular hypertension.

METHODS: This phase IV, multicenter, prospective, observational, open-label, 18-month study (ARGOS) enrolled adult patients with open-angle glaucoma or ocular hypertension who were scheduled to receive the bimatoprost implant in one or both eyes. Data collected included IOP, use of topical IOP-lowering medications, treatment-emergent adverse events, and central corneal endothelial cell density. The primary endpoint was the proportion of primary (first-treated) eyes that received no additional (new) IOP-lowering treatment per standard medical care through month 6 after the implant administration.

RESULTS: A total of 217 patients (341 eyes) were enrolled, and 132 patients (60.8%) and 203 eyes (59.5%) completed the study. Most patients were on topical IOP-lowering medication before receiving the implant. After implant administration, the proportion of primary eyes that had received no additional treatment was 88.6% (95% confidence interval 86.6-90.6) at month 6 (primary endpoint) and remained high throughout the follow-up: 83.7% (95% confidence interval 80.2-87.3) at month 12 and 77.7% (95% confidence interval 73.4-82.1) at month 18. Intraocular pressure was reduced after implant administration, with mean changes in IOP from baseline at follow-up visits ranging from – 1.0 to – 2.0 mm Hg. The mean number of topical IOP-lowering medications used was also reduced, from 1.8 at baseline to 0.9 at month 12 and 1.0 at month 18. Increased IOP and dry eye were the most common ocular treatment-emergent adverse events. The mean percentage change in central corneal endothelial cell density from baseline at month 18 (central reading center evaluation) was – 3.47%. In qualitative interviews, most patients (84%, 21/25) reported overall satisfaction with their treatment outcomes.

CONCLUSIONS: The bimatoprost implant helped control IOP and decrease topical medication use. Throughout the 18 months after implant administration, an estimated 77.7% of eyes required no new added medication for IOP management. Patient-reported outcomes were favorable, and the safety profile of the implant was acceptable.

CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov identifier NCT04647214, registered 23 November, 2020.

PMID:39946034 | DOI:10.1007/s40265-025-02157-1

Trop Anim Health Prod. 2025 Feb 13;57(2):59. doi: 10.1007/s11250-025-04308-8.

ABSTRACT

The purpose of this study was to examine the effects of anti-galactagogue (sage, parsley extract) and anti-inflammatory (echinacea extract) feed supplements on prolactin levels and fertility in the re-pregnancy of lactating Merino ewes. Eighty ewes were randomly assigned to one of two groups: control and treatment. In treatment group (Stop Lactin) group (n = 40) ewes were treated with Stop Lactin® 60 ml on day 0 orally by syringe. The control group (Control) (n = 40), ewes were not treated with any anti-galactagogue feed supplements. On day 0, a vaginal sponge containing 60 mg of medroxyprogesterone acetate was inserted for seven days. On day 7, all ewes received an intramuscular injection of 500 IU PMSG. The study results indicated no statistically significant differences between the Control group and Stop Lactin group in terms of conception rates (87.2% and 78.1%), late embryonic-early fetal mortality rate (20.6% and 8.0%), lambing rate (79.4% and 92%), twin rate (29.6% and 13.0%) and litter size (1.30 and 1.13). Estrus rates (97.5% and 82.1%, p = 0.050) tended to be higher and pregnancy rates (85.0% and 64.1%, p = 0.037) was found to be significant in the control group compared to the Stop Lactin group. The effect of treatment (P = 0.209) on serum prolactin levels and the interaction between treatment × day (P = 0.874) were both found to be insignificant. It is concluded that anti-galactagogue and anti-inflammatory feed supplements did not reduce prolactin concentration and did not improve fertility in lactating Merino ewes.

PMID:39945995 | DOI:10.1007/s11250-025-04308-8

Arch Osteoporos. 2025 Feb 13;20(1):23. doi: 10.1007/s11657-024-01479-z.

ABSTRACT

Through analyzing the data of the NHANES 2007-2020 cycle, this study concluded that high-intensity exercise 1-2 sessions a week can help maintain bone mass, and there is no significant difference from regular exercise more than 3 times a week.

PURPOSE: This study aims to explore the relationship between the various physical activity(PA) patterns and the risk of low bone mineral density(BMD) in Americans of working age.

METHOD: A total of 6482 participants aged 20-60 were selected from the National Health and Nutrition Survey (NHANES) conducted from 2007 to 2020. The PA data of the participants were obtained through individual interviews, and the participants were divided into four groups (inactive, insufficiently active, less frequent but sufficiently active(1-2 sessions a week and PA ≥ 150 min), and regularly active). Weighted logistic regression was used to analyze the correlation between PA patterns and the risk of low BMD. Subgroup analyses were applied to display the correlation between PA patterns and low BMD in different subgroups.

RESULT: After adjusting for confounding factors, the multiple logistic regression model showed that compared with inactive individuals, sufficiently active and regularly active individuals had a 35% (OR, 0.65; 95% CI, 0.46-0.92) and 24% (OR, 0.76; 95% CI, 0.62-0.93) lower risk of low BMD, respectively. Compared with regularly active adults, inactive adults had a 32% (OR, 1.32; 95% CI, 1.07-1.62) increased risk of low BMD, while sufficiently active individuals (OR, 0.85; 95% CI, 0.59-1.23) showed no significant difference compared with regularly active adults.

CONCLUSION: Compared with inactive adults, less frequent but sufficiently active adults have a lower risk of low BMD and showed benefits similar to those in regularly active groups. The sufficiently active pattern may become a new trend in modern working-age adults’ PA patterns.

PMID:39945926 | DOI:10.1007/s11657-024-01479-z