Category: Nevin Manimala

Database (Oxford). 2025 Jan 18;2025:baaf054. doi: 10.1093/database/baaf054.

ABSTRACT

Recent advancements highlight the importance of large-scale causal inference in elucidating disease mechanisms and guiding public health strategies. Mendelian randomization (MR) has become a cornerstone method for identifying causal relationships by leveraging genetic variants as instrumental variables. However, existing tools lack flexibility for multivariable analyses and fail to integrate diverse datasets effectively. To address these challenges, we introduce MRdb, a comprehensive database designed for conducting both univariable and multivariable MR analyses. MRdb encompasses 12 distinct categories of exposure data, including but not limited to 19 126 expression quantitative trait loci genes, 4907 plasma proteins, and 1400 plasma metabolites. Additionally, it integrates 48 507 disease outcomes sourced from FinnGen R10 and the IEU Open GWAS Project. MRdb offers robust data preprocessing features, including handling missing statistics, harmonizing datasets, and selecting instrumental variables to ensure high-quality analyses. Collectively, MRdb bridges the gaps in existing tools by integrating diverse datasets with user-friendly functionalities, empowering researchers to explore complex causal mechanisms.

PMID:40996707 | DOI:10.1093/database/baaf054

Infection. 2025 Sep 25. doi: 10.1007/s15010-025-02645-2. Online ahead of print.

ABSTRACT

Post-tuberculosis lung disease (PTLD) is an increasingly recognized condition that significantly affects survivors’ quality of life, creating disability and incrementing the risk of mortality. PTLD includes a spectrum of structural and functional lung impairments such as obstructive, restrictive, and mixed patterns, bronchiectasis, and pulmonary fibrosis that persist beyond microbiological cure. Global prevalence data highlight a heavy burden of PTLD, especially in high-incidence regions, driven by late diagnosis and suboptimal treatment. Functional and radiological evaluation remains critical for timely diagnosis, with spirometry and imaging revealing lasting abnormalities in a large proportion of TB survivors. Multidisciplinary care is essential and includes bronchodilator therapy, infections/complications management and prevention, pulmonary rehabilitation, and, in selected cases, surgical intervention. Despite increasing recognition, standardized diagnostic and therapeutic pathways for PTLD are still lacking, and data on optimal follow-up, rehabilitation strategies, and preventive measures remain limited. Prospective studies, better stratification tools, and patient education initiatives are urgently needed to reduce PTLD morbidity and mortality. This narrative review synthesizes current evidence on PTLD epidemiology, clinical evaluation and management while offering practical suggestions for clinicians taking care of people with TB and addressing research needs.

PMID:40996670 | DOI:10.1007/s15010-025-02645-2

Adv Ther. 2025 Sep 25. doi: 10.1007/s12325-025-03349-7. Online ahead of print.

ABSTRACT

INTRODUCTION: We compared the real-world effectiveness of initiating beclometasone dipropionate/formoterol fumarate (BDP/FOR) versus fluticasone furoate/vilanterol (FF/VI) in a general practice (GP) asthma cohort in England.

METHODS: Patients newly initiating BDP/FOR or FF/VI between 1 December 2015 and 28 February 2019 (index), were selected from anonymised Clinical Practice Research Datalink data. Baseline was < 12 months pre-index with ≤ 12 months follow-up post-index. Eligible patients were aged ≥ 18 years at index, had diagnosed asthma, ≥ 1 FF/VI or BDP/FOR prescription, medical records eligible for linkage to secondary care data and continuous GP-registration ≥ 12 months pre-index. Patients with chronic obstructive pulmonary disease, ≥ 1 fixed-dose inhaled corticosteroid/long-acting β₂-agonist, single-inhaler triple or biologic therapy at index were excluded. The primary study outcome was asthma exacerbation rate. Secondary outcomes included medication persistence and oral corticosteroid (OCS) use. Propensity scores were generated for each treatment comparison; inverse probability of treatment weighting adjusted for confounding in baseline characteristics between groups, applied to each outcome separately. Analyses considered intercurrent events (ICEs; treatment switching, discontinuation, loss to follow-up, death, rescue medication use).

RESULTS: Weighted group standard mean differences showed adequate balance for most covariates. Patients initiating BDP/FOR (n = 46,809) and FF/VI (n = 3773) had numerically similar exacerbation rates per person per year (PPPY) while-on index treatment [measuring outcome until ICE; BDP/FOR, 0.1479 (n = 31,715); FF/VI, 0.1338 (n = 2547); rate ratio 0.9048, p = 0.2841]. Patients continuing uninterrupted index treatment for 12 months had a lower exacerbation rate PPPY for FF/VI [0.0681 (n = 384)] than BDP/FOR [0.1104 (n = 3342); rate ratio, 0.6162 (p = 0.0293)]. For patients initiating FF/VI versus BDP/FOR, treatment persistence was greater [hazard ratio, 0.76 (p < 0.0001)].

CONCLUSION: Overall, patients initiating FF/VI and BDP/FOR had numerically similar exacerbation rates; of the patients continuing 12 months’ uninterrupted treatment, the FF/VI group had a lower exacerbation rate versus BDP/FOR. Patients initiating FF/VI were less likely to discontinue treatment than those initiating BDP/FOR.

PMID:40996636 | DOI:10.1007/s12325-025-03349-7

Pharmacoeconomics. 2025 Sep 25. doi: 10.1007/s40273-025-01541-9. Online ahead of print.

ABSTRACT

OBJECTIVE: This study examines the generalizability of foreign economic evaluations to the Spanish healthcare system. The research aims to describe the cross-country adaptation methods identified in a scoping review of multinational cost-utility analyses and to examine the probability of concordant funding decisions between Spanish and foreign results, as well as to identify factors influencing generalizability.

METHODS: First, a scoping review of multinational studies reporting cost-utility analyses for at least two countries, including Spain, was conducted using MEDLINE, PubMed, Embase and Web of Science in April 2025. Data related to transferability were extracted and a narrative synthesis was performed. Second, a dataset of case comparisons-each defined as a technology against a comparator in a specific population-was developed from the identified studies. Each foreign comparison was matched to its Spanish equivalent within the same study. Incremental cost-effectiveness ratios (ICERs) were converted to 2024 Spanish Euros and compared against a threshold of €30,000 per quality-adjusted life year (QALY). A multilevel logit model was used, with a binary variable indicating decision concordance between Spanish and foreign ICERs/dominance as the dependent variable. We also analysed the distances in the incremental costs and incremental QALYs between countries using a log-normal bivariate model. Country-specific and other study-related factors were considered as independent variables in both models.

RESULTS: The review included 57 studies. Most were funded by drug manufacturers and conducted in Europe. The majority of authors did not specify their reasons for selecting countries. All but three studies attempted to use local costs, probabilities and/or epidemiological data. Twelve studies incorporated country-specific utilities. A total of 644 comparisons were analysed; 142 were Spanish results and 502 were foreign results with their Spanish equivalents. The cost-effectiveness plane quadrant of the foreign result matched the Spanish result in 84% of cases. Assuming a threshold of €30,000 per QALY, the funding decisions were the same in 93% of cases. The probability of decision concordance was higher when the study was conducted in a Eurozone country or in the United Kingdom. Sensitivity analysis showed the variability of decisions depending on the selected cost-effectiveness threshold. Similar variables were found as relevant factors explaining the distance in the incremental QALYs analysis.

CONCLUSION: Foreign cost-effectiveness results of those studies analysing drugs from Eurozone countries such as France, Germany, Italy, or from the United Kingdom can often be generalizable and provide meaningful insights for decision making in Spain. However, these findings should not be used as a reason to avoid country-specific studies if they are feasible. Further research is needed to determine if these findings apply to other health technologies. Limitations of the study include the lack of a formal assessment of the methodological quality of the selected studies and the potential risks of bias.

PMID:40996621 | DOI:10.1007/s40273-025-01541-9

Inflammopharmacology. 2025 Sep 25. doi: 10.1007/s10787-025-01965-x. Online ahead of print.

ABSTRACT

Rheumatoid arthritis (RA) is a chronic autoimmune disease characterized by persistent inflammation, joint destruction, and systemic complications. Despite the availability of conventional therapies, limitations such as adverse effects and incomplete remission necessitate alternative treatment options. Naringenin, a flavanone found abundantly in citrus fruits, exhibits anti-inflammatory, immunomodulatory, and antioxidant properties, making it a potential therapeutic agent for RA. This systematic review and meta-analysis aimed to evaluate the efficacy of naringenin in preclinical in vivo models of RA by synthesizing available evidence on its therapeutic effects on clinical, biochemical, and histopathological parameters. A comprehensive literature search was conducted in PubChem, Google Scholar, and Science Direct following PRISMA 2020 guidelines. Twelve eligible in vivo studies were identified using established inclusion criteria. Data were extracted for arthritis scores, paw volume, body weight, inflammatory cytokines, oxidative stress markers, histopathological outcomes, and cartilage degradation enzymes. Statistical analyses were performed using RevMan 5.4, and effect sizes were calculated as standardized mean differences (SMD) with 95% confidence intervals (CI) under a random-effects model. Naringenin significantly reduced arthritis severity (SMD = – 3.50), paw volume (SMD = – 1.78), and levels of TNF-α (SMD = – 4.94), IL-6 (SMD = – 2.97), IL-1β (SMD = – 5.55), and IL-17 (SMD = – 1.22), while improving antioxidant defenses (SOD, GSH) and reducing oxidative stress (MDA). It also improved histopathology and body weight, and decreased cartilage-degrading enzymes (MMP-3, MMP-9). Heterogeneity was generally low to moderate across analyses. Subgroup analyses revealed that therapeutic outcomes varied by arthritis model, dosage, and treatment duration. Naringenin demonstrates strong anti-arthritic effects in animal models through modulation of inflammatory cytokines, oxidative stress markers, and joint pathology. These findings support its potential as a candidate for further investigation in clinical settings. However, translational studies and human trials are essential to validate its safety, efficacy, and pharmacokinetics in RA management.

PMID:40996618 | DOI:10.1007/s10787-025-01965-x

J Urban Health. 2025 Sep 25. doi: 10.1007/s11524-025-01004-8. Online ahead of print.

ABSTRACT

The escalating threat of depression demands urgent action from the research community. As a policy that prioritizes a people-centered approach, the New-type Urbanization Policy (NTU) holds promise for alleviating depression. However, whether and how NTU positively affects individual mental health remains underexplored. This study draws on three waves of data from the China Health and Retirement Longitudinal Survey (CHARLS) and employs the difference-in-differences (DID) method as a quasi-natural experiment to empirically analyze the effects of NTU on individual depression. The results indicate that NTU significantly reduces depression, with environmental pollution serving as a mediator in this relationship. Moreover, NTU’s impact on depression reduction is more pronounced in non-resource-based cities and those with lower population concentration. Additionally, the ecosocial theory emphasizes that health arises from the biological embodiment of structural exposures embedded in social and ecological environments. Based on this theory, it serves as a theoretical framework for analyzing NTU’s impact on depression. This study expands the existing research on pilot policies related to individual health and provides concrete policy recommendations for mitigating depression in the context of NTU implementation.

PMID:40996606 | DOI:10.1007/s11524-025-01004-8

Acta Biotheor. 2025 Sep 25;73(4):15. doi: 10.1007/s10441-025-09506-3.

NO ABSTRACT

PMID:40996605 | DOI:10.1007/s10441-025-09506-3

Mol Divers. 2025 Sep 25. doi: 10.1007/s11030-025-11360-x. Online ahead of print.

ABSTRACT

Respiratory syncytial virus (RSV) is a leading cause of severe lower respiratory tract infections in infants, the elderly, and immunocompromised individuals worldwide. The pathogenic mechanism of RSV is closely linked to the membrane fusion process mediated by its fusion glycoprotein (F protein), which has consequently emerged as a critical target for developing anti-RSV therapeutics. At present, there is a lack of specific clinical treatments for RSV, and traditional drug discovery approaches are often time-consuming and expensive. In this context, quantitative structure-activity relationship (QSAR)-assisted drug design offers notable advantages. In this study, we collected a dataset consisting of 156 benzimidazole derivatives against F protein from publicly available sources. Transferable, reproducible, and interpretable 2D-QSAR inhibitory activity and cytotoxicity prediction models were constructed using Genetic Algorithm (GA) and Multiple Linear Regression (MLR). Following rigorous statistical validation, the best inhibitory activity model achieved R² = 0.8740, $Q_{\text{Loo}}^2$ = 0.8272, $R_{\text{test}}^2$ = 0.8273, $Q_{\text{Fn}}^2$ = 0.8033-0.8492, CCC_test = 0.8782, MAE_test = 0.3014; the best cytotoxicity model was of R² = 0.7573, $Q_{\text{Loo}}^2$ = 0.6926, $R_{\text{test}}^2$ = 0.7707, $Q_{\text{Fn}}^2$ = 0.7298-0.8656, CCC_test = 0.8639, MAE_test = 0.1342. The optimal inhibitory activity model was used to perform virtual screening on 912 benzimidazole derivatives retrieved from the PubChem, and identified 234 derivatives with better inhibitory activity than the reference JNJ-53718678. Among these, 152 derivatives were found to possess better docking binding energies than JNJ-53718678. Furthermore, we used the optimal toxicity model to assess their cytotoxicity, and identified 23 derivatives with predicted cytotoxicity lower than that of JNJ-53718678. Finally, through drug-likeness evaluation, ADMET analysis and molecular dynamics simulation, we obtained eight potential RSV inhibitors with higher inhibitory activity, lower cytotoxicity, and better pharmacokinetic properties compared to JNJ-53718678.

PMID:40996593 | DOI:10.1007/s11030-025-11360-x

Neotrop Entomol. 2025 Sep 25;54(1):98. doi: 10.1007/s13744-025-01319-w.

ABSTRACT

Insect pests in stor ed products cause qualitative and quantitative losses in seed lots, reducing their commercial value by directly compromising the physiological and sanitary quality of the seeds. The objective of this study was to evaluate the physiological quality and perform a proximate analysis of rice seeds infested with Sitophilus zeamais Motschulsky (Coleoptera: Curculionidae), using radiographic images. The X-ray analysis was used to detect and identify the weevil development stages and quantify the percentage of infestation in rice seeds. The physiological quality and the proximate analysis were evaluated after the seeds were subjected to four levels of infestation by S. zeamais: 0%, 2%, 3%, and 5%. The radiographic images enabled efficient detection of infestation levels, identification of the weevil’s developmental stages, and assessment of damaged and empty seeds. The following physiological tests were performed: germination test, first germination count test, emergency test, retention capacity of the substrate, emergency speed index, and electrical conductivity test. For the physiological and proximate analysis, the experimental design was completely randomized, with four treatments and four replications. Statistical differences were observed in physiological assessments and proximate analysis across infestation levels, confirming that infestation intensity directly affects seed viability and nutritional value. This emphasizes the importance of effective monitoring methods to mitigate pest damage to stored seeds.

PMID:40996591 | DOI:10.1007/s13744-025-01319-w

Int J Comput Assist Radiol Surg. 2025 Sep 25. doi: 10.1007/s11548-025-03503-0. Online ahead of print.

ABSTRACT

PURPOSE: Acute pulmonary embolism (APE) is a common pulmonary condition that, in severe cases, can progress to right ventricular hypertrophy and failure, making it a critical health concern surpassed in severity only by myocardial infarction and sudden death. CT pulmonary angiogram (CTPA) is a standard diagnostic tool for detecting APE. However, for treatment planning and prognosis of patient outcome, an accurate assessment of individual APEs is required.

METHODS: Within this study, we compiled and prepared a dataset of 200 CTPA image volumes of patients with APE. We then adapted two state-of-the-art neural networks; the nnU-Net and the transformer-based VT-UNet in order to provide fully automatic APE segmentations.

RESULTS: The nnU-Net demonstrated robust performance, achieving an average Dice similarity coefficient (DSC) of 88.25 ± 10.19% and an average 95th percentile Hausdorff distance (HD95) of 10.57 ± 34.56 mm across the validation sets in a five-fold cross-validation framework. In comparison, the VT-UNet was achieving on par accuracies with an average DSC of 87.90 ± 10.94% and a mean HD95 of 10.77 ± 34.19 mm.

CONCLUSIONS: We applied two state-of-the-art networks for automatic APE segmentation to our compiled CTPA dataset and achieved superior experimental results compared to the current state of the art. In clinical routine, accurate APE segmentations can be used for enhanced patient prognosis and treatment planning.

PMID:40996587 | DOI:10.1007/s11548-025-03503-0