Tag: nevin manimala

Clin Infect Dis. 2025 Mar 24:ciaf152. doi: 10.1093/cid/ciaf152. Online ahead of print.

ABSTRACT

BACKGROUND: In 2010, the World Health Organization (WHO) increased recommended doses of first-line tuberculosis (TB) drugs for children. This systematic review aimed to determine the proportion of children who develop adverse events (AEs) on first-line TB treatment and to determine whether there has been a change in toxicity observed with WHO 2010 dosing.

METHODS: We searched MEDLINE, Embase, Scopus, Cochrane Database of Systematic Reviews, WHO Global Index Medicus, and ClinicalTrials.gov for studies that reported AEs for children and adolescents ≤19 years old with TB disease receiving first-line medications. A meta-analysis of proportions was performed to generate pooled proportions of AEs. The protocol was registered with the International Prospective Register of Systematic Reviews (CRD42023418496).

RESULTS: Forty studies comprising 5,021 participants were included. 682 (13.6%) participants experienced 712 AEs; 60 (1.2%) participants experienced a change in therapy due to an AE. The proportion of children with any AE was significantly higher with WHO 2010 dosing (26%, 95% CI 18-34%) compared to pre-WHO 2010 dosing (8%, 95% CI 4-15%), as was the proportion of children who developed severe AEs. There was no statistically significant difference in hepatotoxicity before and after 2010 dosing recommendations, however, significant increases in hepatotoxicity were seen in several subgroups with 2010 dosing. There was substantial heterogeneity between studies; none were at high risk of bias.

CONCLUSIONS: Higher dose regimens in children were associated with increased AEs, raising caution for further dose increases and necessitating additional study of treatment tolerability. These findings are limited by publication bias in observational trials.

PMID:40127187 | DOI:10.1093/cid/ciaf152

Brief Bioinform. 2025 Mar 4;26(2):bbaf119. doi: 10.1093/bib/bbaf119.

ABSTRACT

Accurately predicting the pathogenicity of missense variants is crucial for improving disease diagnosis and advancing clinical research. However, existing computational methods primarily focus on general pathogenicity predictions, overlooking assessments of disease-specific conditions. In this study, we propose DS-MVP, a method capable of predicting disease-specific pathogenicity of missense variants in human genomes. DS-MVP first leverages a deep learning model pre-trained on a large general pathogenicity dataset to learn rich representation of missense variants. It then fine-tunes these representations with an XGBoost model on smaller datasets for specific diseases. We evaluated the learned representation by testing it on multiple binary pathogenicity datasets and gene-level statistics, demonstrating that DS-MVP outperforms existing state-of-the-art methods, such as MetaRNN and AlphaMissense. Additionally, DS-MVP excels in multi-label and multi-class classification, effectively classifying disease-specific pathogenic missense variants based on disease conditions. It further enhances predictions by fine-tuning the pre-trained model on disease-specific datasets. Finally, we analyzed the contributions of the pre-trained model and various feature types, with gene description corpus features from large language model and genetic feature fusion contributing the most. These results underscore that DS-MVP represents a broader perspective on pathogenicity prediction and holds potential as an effective tool for disease diagnosis.

PMID:40127180 | DOI:10.1093/bib/bbaf119

Bull Math Biol. 2025 Mar 24;87(5):56. doi: 10.1007/s11538-025-01428-y.

NO ABSTRACT

PMID:40126575 | DOI:10.1007/s11538-025-01428-y

Can J Exp Psychol. 2025 Mar 24. doi: 10.1037/cep0000372. Online ahead of print.

ABSTRACT

The goal of this article was to determine if second language (L2) speakers benefit from living in mixed-language environments and whether said benefit applies across proficiency levels. To this end, we reanalyzed a subset of data from Gilbert et al. (2019) considering language entropy scores as a proxy for linguistic environment predictability. The task involved producing sentences designed around oronyms in French and English. Participants produced sentences in both languages, allowing the comparison of first language and L2 productions. Their results demonstrated the production of L2-appropriate prosodic cues, albeit after having reached a high level of L2 proficiency. Adding language entropy scores to the original statistical models revealed significant interactions suggesting that participants benefited from living in a mixed-languages environment whereby even low-proficiency speakers produced L2-appropriate prosodic cues. However, low-proficiency L2 speakers living in predictable linguistic environments failed to adapt their prosodic production to their L2, as previously observed. These results suggest that, irrespective of proficiency, the language environment has a significant impact on nonnative language production. This has implications for language development and models of language acquisition. (PsycInfo Database Record (c) 2025 APA, all rights reserved).

PMID:40126574 | DOI:10.1037/cep0000372

Psychol Assess. 2025 Mar 24. doi: 10.1037/pas0001374. Online ahead of print.

ABSTRACT

Gambling disorder (GD) is an officially recognized mental health disorder. However, its conceptualization and diagnostic criteria have changed substantially over the years due to new clinical and epidemiological research supporting its reconceptualization from an impulse control disorder to an addictive disorder. The evolving nature of GD led to changes in its diagnostic approach within the 11^th revision of the International Statistical Classification of Diseases and Related Health Problems (ICD-11). However, no updated standardized psychometric test reflecting the latest developments exists. Therefore, the goal of the present study was to develop and report the psychometric properties of the Gambling Disorder Test (GDT), a brief and convenient four-item assessment instrument reflecting the current diagnostic criteria for GD in the ICD-11. A nationally representative sample of British adults was recruited (N = 1,028, M_age = 46.54 years, SD_age = 15.71). The results showed a one-factor solution for the GDT and initial support for the scale’s factorial validity, population cross-validity, criterion validity, concurrent validity, and reliability. Further gender-based measurement invariance was conducted, with the GDT exhibiting full scalar invariance and the results of latent mean comparison showing that males had significantly higher GD latent means compared to females (latent mean difference = -0.156; z = -3.844, p < .001, d = -.249). The self-reported prevalence of GD in the sample was 0.49%. The GDT is a promising brief assessment instrument based on the latest conceptualization and diagnostic criteria for GD that can be employed by clinicians and researchers alike. (PsycInfo Database Record (c) 2025 APA, all rights reserved).

PMID:40126572 | DOI:10.1037/pas0001374

J Med Internet Res. 2025 Mar 24;27:e57537. doi: 10.2196/57537.

ABSTRACT

BACKGROUND: In-person nutrition and exercise interventions improve physical function in chronic diseases, yet the acceptability and effectiveness of web-based delivery, especially with different levels of personnel support, require further investigation.

OBJECTIVE: This study aims to evaluate a web-based nutrition and exercise intervention delivered entirely digitally from recruitment to trial completion.

METHODS: A randomized controlled trial was conducted using the Heal-Me version 1 platform across 2 levels of personnel support (Light and Intensive). Eligible adults with a history of cancer, chronic lung disease, or liver or lung transplant; internet access; and prior participation in a rehabilitation program were enrolled in a fully web-based program to minimize barriers to exercise participation. Participants were randomly assigned (1:1:1) to 1 of 3 study groups. The control group received a detailed, self-directed digital nutrition and exercise guide. The Heal-Me Light group received the web-based intervention alongside dietitian and exercise specialist-led group classes. The Heal-Me Intensive group received web-based intervention, group classes, and one-to-one sessions with the dietitians and exercise specialists. All participants received a wearable activity tracker. The primary acceptability outcome was adherence to the intervention based on a priori targets. The primary effectiveness outcome was the change in Lower Extremity Functional Scale (LEFS) score. Secondary outcomes included physical function tests, which were performed and measured by videoconference. Questionnaires were used to assess well-being, quality of life, and food intake. Analyses adhered to the intention-to-treat principle.

RESULTS: Of 216 participants, 202 (93.5%) completed the intervention (mean 61, SD 11 years; female: 130/202, 64.4%; cancer: 126/202, 62.4%). Adherence exceeded a priori targets, with 82% (105/128) attending >75% of the program elements including postintervention tests. Participants rated the program as “quite a bit” or “very” useful, with similar ratings between Heal-Me Light (56/64, 88%) and Heal-Me Intensive (51/58, 88%) groups (P=.69). No significant differences were found for changes in LEFS scores (control: mean 0.8, SD 7.7; Heal-Me: mean 0.3, SD 6.6; P=.53). Significant benefits were found in favor of the combined Heal-Me intervention groups versus controls for change in the 2-minute step test, World Health Organization-5 Well-Being Index, Short-Form-36 general, physical health role, energy or fatigue scales, and protein intake. While the change in physical function was similar between the 2 intervention arms, the more intensive one-to-one interaction (Heal-Me Intensive) led to greater improvements in perceived nutrition self-management. No serious adverse events occurred.

CONCLUSIONS: The demonstrated satisfaction, adherence, and effectiveness highlight the high acceptability of a web-based, semisupervised nutrition and exercise intervention delivered entirely digitally in individuals with chronic disease. Future studies may benefit from having a baseline physical function inclusion threshold, the use of a more sensitive primary physical function measure, and a higher intensity digital exercise intervention in exercise-experienced participants.

TRIAL REGISTRATION: Clinicaltrials.gov NCT04666558; https://clinicaltrials.gov/study/NCT04666558.

INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): RR2-10.1016/j.cct.2022.106791.

PMID:40126542 | DOI:10.2196/57537

Arch Ital Urol Androl. 2025 Mar 24:13353. doi: 10.4081/aiua.2025.13353. Online ahead of print.

ABSTRACT

INTRODUCTION: Chronic inflammation is associated to the pathogenesis of prostate cancer (PCa) and benign prostatic hyperplasia (BPH). This study evaluated the correlation between inflammatory markers fibroblast growth factor-2 (FGF2), interleukin (IL)-8, and IL-6 in PCa and BPH tissues to understand their involvement in disease progression.

METHODS: A cross-sectional investigation was carried out, examining prostate specimens from 62 male patients diagnosed with PCA or BPH. Specimens were taken via transurethral resection of the prostate (TURP) and stained with hematoxylin and eosin to look for inflammatory infiltrates and aggressiveness. The levels of FGF2, IL-8, and IL-6 were evaluated using ELISA. Chi-square and logistic regression tests were used in the statistical analysis.

RESULTS: High-grade inflammation was found in all BPH cases (100%), but not in PCa cases. In BPH tissues, elevated levels of IL-8 and IL-6 had a significant correlation with high-grade inflammation (p < 0.05). On the other hand, PCa tissues had considerably greater FGF2 levels than benign tissues (p < 0.05). Elevated FGF2 levels and the lack of high-grade inflammation in PCa tissues point to different pathogenic processes in PCa and BPH.

CONCLUSIONS: This study emphasizes the importance of chronic inflammation in BPH development, with IL-8 and IL-6 playing essential roles. The results imply that treating BPH by focusing on IL-8 and IL-6 may be beneficial. Increased levels of FGF2 in PCa tissues suggest that this protein may be used as a biomarker and therapeutic target for PCa. These findings highlight the importance of targeting both inflammatory and growth factor pathways for treating prostatic disorders.

PMID:40126506 | DOI:10.4081/aiua.2025.13353

JAMA Intern Med. 2025 Mar 24. doi: 10.1001/jamainternmed.2025.0155. Online ahead of print.

ABSTRACT

IMPORTANCE: Although there are increasing differences in health policy and population health across US states over the past decade, little is known about how US states compare with other countries on avoidable mortality.

OBJECTIVE: To compare trends in avoidable mortality across US states and countries in the European Union (EU) and the Organisation for Economic Co-operation and Development (OECD).

DESIGN, SETTING, AND PARTICIPANTS: Retrospective, population-based, repeated cross-sectional study comparing changes in avoidable mortality among decedents aged 0 to 74 years in 50 US states (and Washington, DC) and 40 high-income countries between 2009 and 2021. Data analysis was conducted from May to July 2024.

MAIN OUTCOMES AND MEASURES: Avoidable mortality comprising both preventable deaths related to prevention and public health and treatable deaths related to timely and effective health care treatment.

RESULTS: Between 2009 and 2019, total avoidable mortality increased in all US states (median [IQR], 29.0 [20.1 to 44.2] deaths per 100 000 people), while it decreased in most comparator countries (-14.4 [-28.4 to -8.0]). During this period, variation in avoidable mortality widened across US states (2009: median [IQR], 251.1 [228.4 to 280.4]; 2019: 282.8 [249.1 to 329.5]), but narrowed in comparator countries (2009: 201.5 [166.2 to 320.8]; 2019: 187.1 [152.0 to 298.2]). During the COVID-19 pandemic (2019-2021), avoidable mortality increased for all US states (median [IQR], 101.5 [64.7 to 143.1]) and comparator countries (25.8 [9.1 to 117.7]). The states and countries that experienced the greatest increase in avoidable deaths during the COVID-19 period were those with the highest baseline avoidable mortality (Pearson ρ = 0.86; P < .001). Health spending and avoidable mortality have a consistent, negative, and significant association among comparator countries (2019: Pearson ρ = -0.7; P < .001) but no statistically significant association within US states (2019: Pearson ρ = -0.12; P = .41).

CONCLUSIONS AND RELEVANCE: This cross-sectional study found that the stark contrast in avoidable mortality trends between all US states compared with EU and OECD countries suggests that broad, systemic factors play a role in worsening US population health. While other countries appear to make gains in health with increases in health care spending, such an association does not exist across US states, raising questions regarding US health spending efficiency.

PMID:40126499 | DOI:10.1001/jamainternmed.2025.0155

Arch Ital Urol Androl. 2025 Mar 24:13750. doi: 10.4081/aiua.2025.13750. Online ahead of print.

ABSTRACT

INTRODUCTION AND OBJECTIVES: N-acetyl-cysteine (NAC) is one of the oldest and most powerful antioxidants used to treat various diseases. It plays an important role in protecting cells against oxidative damage and has the potential to improve seminal parameters in male with infertility. This systematic review and meta-analysis aim to comprehensively evaluate the efficacy and safety profile of antioxidant supplementation with NAC in male with infertility or impaired semen parameters.

MATERIALS AND METHODS: This systematic review and meta-analysis adhered to Cochrane Handbook guidelines. A literature search across PubMed, ScienceDirect, Cochrane Library and Scopus on February 21, 2024 of studies evaluating NAC supplementation for male infertility or impaired semen parameters was conducted. Study quality was assessed using Revised Cochrane’s risk of bias (RoB 2.0) and RevMan 5.4 was used for meta-analysis.

RESULTS: Search yielded 1.106 articles and 5 studies were included in this meta-analysis. Our study showed that patients who received NAC had statistically significant results in improving sperm volume [MD: 0.69 (0.26-1.12), P = 0.002], sperm concentration [MD: 4.43 1.50-7.36), P = 0.003], sperm total motility [MD: 9.69 (6.61-12.77), P < 0.00001], and normal sperm morphology [MD: 1.36 (0.70-2.03), P < 0.0001] compared to control. Additionally, patients given NAC had no reported side effects based on our included studies.

CONCLUSIONS: We found NAC supplementation significantly improves seminal parameters and has a favorable safety profile. These findings highlight the potential role of NAC as a safe supplementation for male with infertility or in male with impaired semen parameters.

PMID:40126496 | DOI:10.4081/aiua.2025.13750

JAMA Netw Open. 2025 Mar 3;8(3):e251533. doi: 10.1001/jamanetworkopen.2025.1533.

ABSTRACT

IMPORTANCE: Potentially preventable hospitalization rates are widely endorsed quality indicators that have been used to evaluate the impact of policies on access to high-quality primary and ambulatory care for children. Although potentially preventable hospitalization rates have been decreasing, little is known about how these trends are associated with the exclusive reliance on inpatient data, which omit observation status, a common designation for pediatric hospital stays.

OBJECTIVE: To assess the implications of omitting observation stay data on potentially preventable hospitalization rate calculations over time.

DESIGN, SETTING, AND PARTICIPANTS: In this retrospective cross-sectional study, inpatient and observation stays for patients aged 6 to 17 years related to pediatric ambulatory care sensitive conditions (ACSCs), were identified from the Healthcare Cost and Utilization Project state-specific databases from Georgia, Iowa, Maryland, Nebraska, and Vermont, 2010 to 2019, and from Wisconsin, 2012 to 2019. The units of analysis include an overall aggregate level, state level, and county level. Data were analyzed from February to November 2024.

MAIN OUTCOME AND MEASURES: The main outcome was the pediatric quality indicator overall composite of potentially preventable hospitalization rates (hereafter the composite hospitalization rate) and was calculated using inpatient-only and combined (ie, inpatient and observation) hospital stay data per 100 000 children.

RESULTS: Among a total of 64 846 identified hospital stays (median [IQR] age, 10 [8-14] years for inpatient stays and 10 [7-13] for observation stays; 32 733 [50.5%] male; 573 [0.9%] Asian or Pacific Islander, 20 042 [30.9%] Black, 3413 [5.3%] Hispanic, 168 [0.3%] American Indian or Alaska Native, 22 970 [35.4%] White, and 1842 [2.8%] Other), 22 275 (34.4%) were observation stays. The use of observation stays grew from 2090 of 6923 stays (30.2%) in 2010 to 2525 of 5531 stays (45.7%) in 2019. When using inpatient-only data, the overall aggregate-level composite hospitalization rate per 100 000 children was 141.7 in 2010 and decreased to 71.0 in 2019, and the annual percentage change was -6.8% (95% CI, -6.8% to -6.8%; P < .001). When using combined data, the composite hospitalization rate was 203.0 in 2010 and 130.7 in 2019, respectively, with an annual percentage change of -4.5% (95% CI, -4.5% to -4.5%; P < .001). Most state-level and county-level composite hospitalization rates exhibited declining trends when using inpatient-only data. After combining observation stay data, the declines were attenuated or even reversed in some cases.

CONCLUSION AND RELEVANCE: Decreases in the composite hospitalization rate for pediatric ACSCs were associated with the shifting of patient status from inpatient to observation stays. These findings emphasize the need for standardized reporting and inclusion of observation stay data to support disease surveillance, policy evaluation, and decision-making.

PMID:40126481 | DOI:10.1001/jamanetworkopen.2025.1533