Nevin Manimala

BMC Glob Public Health. 2025 Sep 12;3(1):76. doi: 10.1186/s44263-025-00189-z.

ABSTRACT

BACKGROUND: Non-pharmaceutical interventions (NPIs) in response to the COVID-19 pandemic necessitated a trade-off between the health impacts of viral spread and the social and economic costs of restrictions. Navigating this trade-off proved consequential, contentious, and challenging for decision-makers.

METHODS: We conduct a cost-effectiveness analysis of NPIs enacted at the state level in the United States (US) in 2020. We combine data on COVID-19 cases, deaths, policies, and the social, economic, and health consequences of infections and interventions within an epidemiological model. We estimate SARS-CoV-2 prevalence, transmission rates, effects of interventions, and costs associated to infections and NPIs in each US state. We use these estimates to quantitatively evaluate the efficacy and gross impacts of the policy schedules implemented during the pandemic. We also derive optimal cost-effective strategies that minimize aggregate costs to society.

RESULTS: We find that NPIs were effective in substantially reducing SARS-CoV-2 transmission, averting 860,000 (95% CI: 560,000-1,190,000) COVID-19 deaths in the US in 2020. Although school closures reduced transmission, their social impact in terms of student learning loss was too costly, depriving the nation of $2 trillion in 2020 US dollars (USD2020), conservatively, in future Gross Domestic Product (GDP). Moreover, this marginal trade-off between school closure and COVID-19 deaths was not inescapable: a combination of other measures would have been enough to maintain similar or lower mortality rates without incurring such profound learning loss. Optimal policies involve consistent implementation of mask mandates, public test availability, contact tracing, social distancing orders, and reactive workplace closures, with no closure of schools. Their use would have reduced the gross impact of the pandemic in the US in 2020 from $4.6 trillion to $1.9 trillion and, with high probability, saved over 100,000 lives.

CONCLUSIONS: US COVID-19 school closure was not cost-effective, but other measures were. While our study focuses on COVID-19 in the US prior to vaccines, our methodological contributions and findings about the cost-effectiveness and optimal structure of NPI policies have implications for the response to future epidemics and in other countries. Our results also highlight the need to address the substantial global learning deficit incurred during the pandemic.

PMID:40936091 | DOI:10.1186/s44263-025-00189-z

BMC Plant Biol. 2025 Sep 12;25(1):1201. doi: 10.1186/s12870-025-07214-1.

ABSTRACT

BACKGROUND: Arbuscular mycorrhizal fungi (AMF) can stimulate root development in plants and enhance their ability to adapt to stress conditions. This study investigated the effects of arbuscular mycorrhizal fungi (AMF) inoculation on the growth, hormone dynamics, and phosphorus (P) metabolism of two wheat cultivars with differing phosphorus utilization efficiencies under both normal and low phosphorus concentration conditions. The research focused on the symbiotic interaction between AMF and these wheat varieties to elucidate their responses to varying phosphorus availability.

RESULT: The experiment showed that phosphorus inefficient wheat SW14 inoculated with AMF for 30 days under low phosphorus stress showed significant enhancement in plant height, biomass, leaf width, stem thickness, root surface area, and vegetative phosphorus content, while total root length and primary root length were reduced, This change in root length was attributed to the fact that the root system undergoes elongation and growth to adapt to the adversity under low phosphorus stress in crops, and inoculation with AMF effectively alleviated the extent of this low phosphorus stress. while IAA, SL, cellulose and lignin hormone levels and APC enzyme activities were significantly elevated, and stem structure was significantly optimized; whereas, the phosphorus-efficient variety, SW2, did not show significant improvement due to its own unique tolerance to low phosphorus stress (Table 2). Transcriptomic profiling identified 2,500 differentially expressed genes (DEGs: 983↑/1,517↓), enriched in ABC transporters (ko02010), Plant hormone signal transduction (ko04075), and MAPK signaling pathway – plant (ko04016), Cutin, suberin and wax biosynthesis(ko00073). WGCNA further resolved that AMF responded to low phosphorus stress by up-regulating the expression of cellulose, lignin, APC synthesis, and IAA/SL-related genes in SW14, with the most relevant phenotypes shown to correlate to primary root length, total root length, root dry weight and stem diameter.

CONCLUSION: AMF inoculation significantly enhanced growth and dry matter accumulation in the low-phosphorus-use-efficiency wheat variety SW14 under phosphorus-deficient stress. This treatment concurrently stimulated IAA, SL, and APC activities, resulting in increased phosphorus uptake/accumulation, notable accumulation of cellulose and lignin, and consequently significantly improved stem strength. Although AMF inoculation improved growth in the high-phosphorus-use-efficiency wheat variety SW2, these enhancements failed to reach statistical significance.

PMID:40936089 | DOI:10.1186/s12870-025-07214-1

Epigenetics Chromatin. 2025 Sep 12;18(1):59. doi: 10.1186/s13072-025-00626-1.

ABSTRACT

DNA-methylation is a key epigenetic mark in chromatin that attenuates chromatin accessibility during transcription, implying a crucial role in gene regulation. Its symmetrical distribution and function is thought to be linked to the periodicity of the DNA helix and the positioning of DNA wrapped around the nucleosome. Epigenomic data suggest that DNA methyltransferases (DNMTs) can methylate DNA when wrapped around a histone octamer. Yet, how this is precisely linked to positioning and periodicity is yet to be elucidated. It has been hypothesized that the observed methylation patterns may be related to the changing accessibility of nucleosome-bound DNA to DNMTs. Here, incorporating NOMe-Seq data, which simultaneously measures nucleosome positioning and DNA methylation at CpG sites across the genome, the interaction of DNMT1 with nucleosomal DNA could be mechanistically modeled and compared to hypothesized dependencies. Furthermore, X-ray structures of DNMT1 were superimposed onto those of nucleosome core complexes at base resolution to determine which histone-bound DNA positions would be sterically accessible or inaccessible to DNMTs. Statistical comparison with experimental NOMe-Seq data revealed that structurally computed DNA accessibility scores can indeed explain DNA methylation patterns in actively transcribed regions with positioned high nucleosome density.

PMID:40936088 | DOI:10.1186/s13072-025-00626-1

BMC Res Notes. 2025 Sep 11;18(1):386. doi: 10.1186/s13104-025-07416-8.

NO ABSTRACT

PMID:40936084 | DOI:10.1186/s13104-025-07416-8

Cardiovasc Diabetol. 2025 Sep 11;24(1):360. doi: 10.1186/s12933-025-02860-z.

ABSTRACT

BACKGROUND: Insulin resistance (IR) has been recognized as a critical factor in the progression of cardiovascular disease (CVD), yet its association with cardiovascular-kidney-metabolic (CKM) syndrome remains incompletely understood. This study aimed to evaluate the impact of IR, as measured by the estimated glucose disposal rate (eGDR), on the risk of future CVD events in individuals with CKM stages 0-3.

METHODS: This study included 325,312 participants from the UK Biobank with CKM stages 0-3. IR was quantified using eGDR, a non-insulin-dependent metric, with lower values indicating greater IR. Participants were stratified into quartiles based on eGDR distribution. The primary outcome was incident CVD, including coronary heart disease, stroke, atrial fibrillation, heart failure, and peripheral artery disease.

RESULTS: In the CKM 0-3 cohort, eGDR demonstrated the highest predictive value for future CVD events among non-insulin-dependent IR metrics. Incorporating eGDR significantly improved the predictive performance of the PREVENT Cardiovascular Disease Risk Equations (AUC: PREVENT Equations + eGDR 0.743 vs. PREVENT Equations 0.719, p < 0.001). Over a median follow-up of 13.57 years, 48,433 incident CVD cases were identified. The adjusted rates of CVD incidence (95% confidence interval [CI]) across eGDR quartiles (Q1-Q4) were 3.84 (3.62-4.07), 3.82 (3.66-3.98), 3.53 (3.41-3.65), and 3.37 (3.25-3.50) per 1000 person-years. RCS analysis revealed a significant nonlinear association between eGDR and CVD incidence (p for overall < 0.001; p for nonlinear = 0.020), with greater risk reduction at higher eGDR levels. A significant trend toward reduced CVD risk was observed across higher eGDR quartiles, with Q3 and Q4 demonstrating statistically significant reductions relative to Q1 (HR 0.920, 95% CI 0.871-0.971; and 0.883, 95% CI 0.827-0.942, respectively; p for trend < 0.001). Kaplan-Meier analysis further confirmed a graded decrease in CVD risk with increasing eGDR levels (log-rank p < 0.001).

CONCLUSION: This study establishes a strong association between IR severity and long-term CVD risk in individuals with CKM syndrome stages 0-3. The eGDR, a reliable surrogate marker of IR, independently predicts future CVD events and provides incremental predictive value beyond the PREVENT equations. These findings underscore the clinical utility of eGDR for risk stratification in CKM populations.

PMID:40936079 | DOI:10.1186/s12933-025-02860-z

Int J Colorectal Dis. 2025 Sep 12;40(1):196. doi: 10.1007/s00384-025-04995-7.

ABSTRACT

PURPOSE: Fistula Laser Closure (FiLaC®) is a sphincter-preserving technique for anal fistulas, but its efficacy and safety remain under discussion. Therefore, we aim to evaluate the efficacy and safety of FiLaC® in the management of patients with cryptoglandular fistulas.

METHODS: A systematic review was performed in MEDLINE, Embase, and Cochrane databases in January 2025, following PRISMA guidelines. We included randomized controlled trials (RCTs) and observational studies assessing FiLaC® for cryptoglandular fistulas, with or without surgical adjunctive measures. The main outcome was the primary healing rate. Secondary outcomes included fistula recurrence, incontinence, reoperation rates, and postoperative complications. Subgroup analyses explored variables related to the primary healing rate. Data are presented as percentages (95% confidence interval). Statistical analyses were performed using R (version 4.4.1 (2024-06-14 (ucrt)).

RESULTS: We included 24 studies with 1,503 patients. The pooled primary healing rate was 57.46% (49.40-65.33). Recurrence occurred in 18.48% of patients (10.14-28.47), while new-onset incontinence was rare (0.57%; 0.00-2.15). The reoperation rate was 36.49% (28.95-44.36), and anal abscesses or infections affected 6.54% (1.93-13.09) of patients. Subgroup analysis showed no statistically significant differences in the primary healing rate based on fistula type, adjunctive measures, or sex. Sensitivity analysis confirmed the robustness of our findings.

CONCLUSIONS: FiLaC® seems to be a safe option with an intermediate healing rate in patients with cryptoglandular fistulas, although it is associated with a considerable recurrence rate. While its sphincter preservation advantage is evident, further RCTs standardizing the technique and adjunctive approaches are needed to optimize outcomes and refine its application in fistula management.

PMID:40936062 | DOI:10.1007/s00384-025-04995-7

Int J Clin Oncol. 2025 Sep 11. doi: 10.1007/s10147-025-02870-7. Online ahead of print.

ABSTRACT

PURPOSE: Uveal melanoma (UM) is the most common primary intraocular malignancy in adults, yet comprehensive nationwide epidemiologic data remain limited. This study aimed to provide an updated analysis of UM incidence, survival, and disparities in the United States (US) using near-complete population coverage.

METHODS: We analyzed data from the North American Association of Central Cancer Registries (NAACCR) and US Cancer Statistics (USCS) program between 1995 and 2018, covering 98-100% of the US population. Age-adjusted incidence rates (AAIRs) and relative survival were calculated using SEER*Stat and Joinpoint regression.

RESULTS: A total of 37,917 UM cases were identified, with an overall AAIR of 5.54 per million (95% CI: 5.48-5.59), showing a stable but slightly increasing trend (AAPC = 0.06). Incidence was highest in non-Hispanic whites (6.87 ppm), men (6.25 ppm), and those aged 75-79 years. Geographic variation was notable, with peak incidence in Oregon and Iowa. Most tumors (81.3%) were localized at diagnosis, and 27.4% of patients had another primary malignancy. 5- and 10-year relative survival rates were 83.3% and 73.9%, respectively, with worse outcomes in metastatic disease. A shift toward radiotherapy, especially brachytherapy, was observed, although survival gains remained limited.

CONCLUSIONS: This nationwide study refines US UM incidence estimates and highlights persistent disparities by sex, race, age, and geography. The high prevalence of secondary malignancies underscores the need for genetic counseling and extended surveillance. Despite advances in imaging, local therapies (e.g., brachytherapy, proton therapy), and emerging systemic approaches including immunotherapy, survival improvements in advanced UM remain limited.

PMID:40936061 | DOI:10.1007/s10147-025-02870-7

Int Urol Nephrol. 2025 Sep 11. doi: 10.1007/s11255-025-04788-5. Online ahead of print.

ABSTRACT

BACKGROUND: Multiple myeloma (MM) is a plasma cell disorder frequently complicated by renal failure and this is associated with high mortality and significant health care costs. It has been estimated in previous studies that 20-40% of patients with MM develop renal impairment to a varying degree during the course of the disease, and up to 10% are described as presenting with severe acute kidney injury when MM is diagnosed. Its economic consequences are prolonged hospital stays and increased costs of care. Our study evaluates two decades of national mortality data to identify patterns and disparities in renal failure-related deaths among adults with MM in the U.S.

METHODS: We analyzed national mortality data using the CDC WONDER database (CDC, 2020), including adults (25-85 + years). Deaths were identified using the ICD-10 Code C90.0 (Multiple Myeloma) AND N17-N19 (Renal failure). Age-adjusted mortality rates calculated per 100,000 were abstracted by sex, race/ethnicity, census region, state, and urbanization. Temporal trends were assessed using Join-point regression models. Annual percentage changes in AAMR were estimated using Monte-Carlo permutation and 95% confidence intervals using the Parametric Method. A two-tailed t-test was employed to measure the statistical significance of APCs.

RESULTS: From 1999 to 2020, mortality trends initially increased for multiple myeloma due to renal failure (ages 25-85 +), then declined across various racial groups, genders, census regions, as well as state and urbanization levels. The overall age-adjusted mortality rate (AAMR) fell from 1.26 per 100,000 in 1999 to 1.02 per 100,000 in 2020. For men, rates increased until 2005 (APC = 1.65%), fluctuated for several years, then declined more sharply after 2012 (falling between 1.88% and 7.32% annually). For women, the increase lasted only until 2002 (APC = 3.64%), followed by a consistent yearly decline of 3.57%. Among racial groups, Asian, Black, and Hispanic communities showed a steady downward trend starting in 1999, decreasing annually by 3.11%, 2.98%, and 2.69%, respectively. Meanwhile, the White populations initially experienced an upward trend, with deaths rising 5.22% per year until 2002, then decreasing at 2.98% per year afterward. Regional trends indicated steady improvements in the Northeast and West, with death rates decreasing by 2.36% and 3.06% annually. The Midwest and South experienced early increases (peaking at 2.72% and 2.73% in 2003) before reversing course to decline annually by 2.97% and 2.82%.

CONCLUSION: From 1999 to 2020, the mortality from MM due to renal failure initially followed a rising trend and then declined among all geographic and demographic groups. These early rises were most evident in males, the White population, the Midwest and South, as well as small metro areas. These varying trends emphasized the need for targeted strategies to lower the renal-related mortality in high-risk multiple myeloma patients.

CLINICAL TRIAL NUMBER: Not applicable.

PMID:40936059 | DOI:10.1007/s11255-025-04788-5

Obes Surg. 2025 Sep 12. doi: 10.1007/s11695-025-08217-5. Online ahead of print.

ABSTRACT

BACKGROUND: Metabolic and bariatric surgery is linked to an increased risk of venous thromboembolism (VTE) and postoperative hemorrhage. Although thrombotic chemoprophylaxis is frequently provided to avert VTE, its impact on bleeding complications remains uncertain.

OBJECTIVES: This study intends to assess the effect of preoperative thrombotic chemoprophylaxis on the occurrence of postoperative hemorrhage in individuals undergoing sleeve gastrectomy.

METHODS: A retrospective cohort study was conducted including 226 individuals who underwent sleeve gastrectomy at KHMC over a 2-year period. Patients were classified into two groups based on the provision of preoperative thromboprophylaxis. Demographic data, comorbidities, and postoperative outcomes were analyzed using descriptive and inferential statistics.

RESULTS: Out of 226 patients, 149 (65.9%) underwent preoperative thromboprophylaxis. Postoperative bleeding occurred in 1.3% of patients. A statistically significant inverse association was identified between thromboprophylaxis and the installation of postoperative drains (P = 0.003). Nonetheless, no significant association was seen between thromboprophylaxis and postoperative bleeding following propensity-score matching (P = 1.00).

CONCLUSION: The preoperative administration of low-molecular-weight heparin (LMWH) did not substantially correlate with an elevated risk of postoperative hemorrhage. However its application was associated with a reduced incidence of postoperative drain placement. These findings enrich the expanding amount of research about the safety and outcomes of thrombotic chemoprophylaxis in metabolic and bariatric surgery.

PMID:40936054 | DOI:10.1007/s11695-025-08217-5

J Ultrasound. 2025 Sep 11. doi: 10.1007/s40477-025-01077-w. Online ahead of print.

ABSTRACT

PURPOSE: B-lines are among the key artifact signs observed in Lung Ultrasound (LUS), playing a critical role in differentiating pulmonary diseases and assessing overall lung condition. However, their accurate detection and quantification can be time-consuming and technically challenging, especially for less experienced operators. This study aims to evaluate the performance of a YOLO (You Only Look Once)-based algorithm for the automated detection of B-lines, offering a novel tool to support clinical decision-making. The proposed approach is designed to improve the efficiency and consistency of LUS interpretation, particularly for non-expert practitioners, and to enhance its utility in guiding respiratory management.

METHODS: In this observational agreement study, 644 images from both anonymized internal and clinical online database were evaluated. After a quality selection step, 386 images remained available for analysis from 46 patients. Ground truth was established by blinded expert sonographer identifying B-lines within rectangular Region Of Interest (ROI) on each frame. Algorithm performances were assessed through Precision, Recall and F1 Score, whereas to quantify the agreement between the YOLO-based algorithm and the expert operator, weighted kappa (kw) statistics were employed.

RESULTS: The algorithm achieved a precision of 0.92 (95% CI 0.89-0.94), recall of 0.81 (95% CI 0.77-0.85), and F1-score of 0.86 (95% CI 0.83-0.88). The weighted kappa was 0.68 (95% CI 0.64-0.72), indicating substantial agreement algorithm and expert annotations.

CONCLUSIONS: The proposed algorithm has demonstrated its potential to significantly enhance diagnostic support by accurately detecting B-lines in LUS images.

PMID:40936046 | DOI:10.1007/s40477-025-01077-w