Nevin Manimala

bioRxiv [Preprint]. 2025 May 27:2025.05.22.655574. doi: 10.1101/2025.05.22.655574.

ABSTRACT

BACKGROUND: Alzheimer’s disease (AD) begins years before symptoms appear, making early detection essential. The medial temporal lobe (MTL) is one of the earliest regions affected, and its network flexibility, a dynamic measure of brain connectivity, may serve as a sensitive biomarker of early decline. Cognitive (acquisition, generalization), genetic (APOE, ABCA7), and biochemical (P-tau217) markers may predict MTL dynamic flexibility. Given the high rate of missing data in AD research, this study uses machine learning with advanced imputation methods to predict MTL dynamic flexibility from multimodal predictors in an aging cohort.

METHODS: In an ongoing study at Rutgers’s Aging and Brain Health Alliance, data from 656 participants are utilized, including cognitive assessments, genetic and blood-derived biomarkers, and demographics. Due to MRI-related constraints, only 34.15% of participants had measurable MTL dynamic flexibility from resting-state fMRI. To estimate MTL dynamic flexibility from available data, we evaluated four missing data handling methods (case deletion, MICE, MissForest, and GAIN), and trained five regression models: Ridge, k-NN, SVR, regression trees (bagging, random forest, boosting), and ANN. Hyperparameters were optimized via grid search with 3-fold cross-validation. Model performance was assessed using mean absolute error (MAE), root mean squared error (RMSE), and runtime through 5-fold cross-validation repeated 25 times to ensure robustness in clinical data settings.

RESULTS: A total of 1,866 missing values (25.86%) were identified in the dataset, with only 42 complete cases (6.40%) remaining after listwise deletion, highlighting the need for effective imputation. In the initial analysis using only complete cases, support vector regression (SVR) achieved the lowest mean absolute error (MAE = 0.184), though overall performance was limited due to small sample size. In the second phase, three imputation techniques were applied, significantly improving model accuracy. MissForest combined with Random Forest produced the best results (MAE = 0.083), representing a 54.7% improvement over case deletion. Statistical analysis confirmed significant differences in performance across imputation methods (p < 0.001), with MissForest outperforming GAIN and MICE. GAIN was the fastest imputation method.

DISCUSSION: The findings underscore the importance of using robust imputation strategies to maximize data utility and model reliability in studies with high missingness. Further research is needed, particularly incorporating additional neuroimaging measures, to localize the brain regions most affected by biomarker-driven changes and to refine predictive models for clinical applications.

PMID:40501856 | PMC:PMC12154674 | DOI:10.1101/2025.05.22.655574

J Pak Med Assoc. 2025 May;75(5):699-703. doi: 10.47391/JPMA.20753.

ABSTRACT

OBJECTIVE: To compare the impact of two different doses of proteins on nitrogen balance and clinical outcomes in critically ill patients.

METHODS: The randomised clinical trial was conducted from November 2020 to May 2021 at the intensive care unit of Shifa International Hospital, Islamabad, Pakistan, and comprised critically ill adult patients of either gender at nutritional risk. They were divided into Group I receiving 1g per kilogramme body weight of protein, and Group II receiving 2g per kilogramme body weight of protein. Sequential Organ Failure Assessment scores were calculated for each case. Data was analysed using SPSS 23.

RESULTS: Of the 88 patients, 45(51.13%) were in Group I; 28(62.2%) males and 17(37.8%) females with mean age 61±3.5 years. There were 43(48.86%) patients in Group II; 30(69.8%) males and 13(30.2%) females with mean age 64.4±11.6 years (p>0.05). There was no significant difference in nitrogen balance between the groups on day 1 (p=0.381). However, by the discharge day, nitrogen balance was significantly improved in Group II compared to Group I (p=0.001). There was a statistically weak negative relationship between nitrogen balance and Sequential Organ Failure Assessment score (r=-0.131). Nitrogen balance had no significant relationship with the number of ventilated days (r=-0.002), intensive care unit days (r=0.043) and length of hospital stay (r=0.089).

CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov, NCT04468503.

CONCLUSIONS: Nitrogen balance was significantly better in the critically ill patients who received 2g protein per kilogramme body weight compared to those receiving 1g protein per kilogramme body weight.

PMID:40500809 | DOI:10.47391/JPMA.20753

Isr J Health Policy Res. 2025 Jun 11;14(1):36. doi: 10.1186/s13584-025-00693-5.

ABSTRACT

BACKGROUND: New vaccines and monoclonal antibody (mAb) against respiratory syncytial virus (RSV) were recently approved for adults and infants, respectively. However, their inclusion in national vaccination programs has been slow. Accurate assessment of RSV disease burden among all ages is essential for the global introduction of these agents.

METHODS: We evaluated all-ages burden of RSV hospitalizations, from 2020 to 2024, based on data collected by a new national laboratory-based hospital surveillance system. RSV-positive respiratory samples from patients hospitalized in general hospitals nationwide were reported. Data were analyzed by RSV circulation periods and age-group to determine hospitalization rates and 30-day mortality (30-DM) rates. We compared the laboratory-confirmed hospitalization rates with rates previously calculated based on ICD-9 codes.

RESULTS: RSV-confirmed hospitalizations were reported for all age-groups. The highest RSV hospitalization rates were found among patients < 1 year old. Patients ≥ 60 years old had the highest RSV hospitalization rates among ≥ 5 years old patients, and their 30-DM rates reached 14.7%, exceeding those of influenza. During the COVID-19 pandemic, lower rates of RSV-confirmed hospitalizations were reported among ≥ 60 years old patients, probably due to higher adherence to social distancing measures. We found higher numbers and rates of laboratory-confirmed hospitalizations among all age-groups ≥ 1 year old, than those previously reported by our group, based on ICD-9 codes.

CONCLUSIONS: Laboratory-confirmation of RSV is paramount for optimal assessment of RSV hospitalization burden, particularly beyond infancy, and for the global adoption of newly developed vaccines and mAb.

PMID:40500807 | DOI:10.1186/s13584-025-00693-5

Infect Dis Poverty. 2025 Jun 11;14(1):46. doi: 10.1186/s40249-025-01314-8.

ABSTRACT

BACKGROUND: Helminthiases are neglected diseases that affect billions of people worldwide, particularly those with inadequate sanitation, poor hygiene practices, and limited access to clean water. Due to frequent underreporting, wastewater-based epidemiology has emerged as a valuable tool for monitoring parasitic infections at population-level. This study aimed to detect and quantify helminth eggs in untreated sewage sludge from eight wastewater treatment plants located in different Brazilian socioeconomic regions.

METHODS: The study was conducted from June 2021 to December 2023 in Goiás and Federal District, the Brazilian federative unit with the highest income inequality. Samples were collected bimonthly (n = 121). Helminth eggs were recovered using centrifugation and flotation with a ZnSO₄ solution (d = 1.30 g/ml). After 21-28 days of incubation in sulfuric acid, viable eggs were identified and counted using a Sedgewick-Rafter Chamber under an optical microscope. Statistical analyses included One-way analysis of variance (ANOVA) followed by Tukey’s multiple comparisons test to evaluate differences in helminth egg counts between low-, medium- and high-income regions.

RESULTS: Twelve helminth genera were identified, revealing significant differences in prevalence and diversity across socioeconomic strata. Cestode eggs, particularly Hymenolepis spp. (44.28%), were the most prevalent overall. Trematode eggs were less frequent but exhibited greater taxonomic diversity. Sludge from low-income areas had the highest egg concentration [16.61 ± 3.02 eggs per gram of dry mass ( eggs/g DM)], nearly five times greater than in high-income areas such as Brasília Norte (3.56 ± 0.55 eggs/g DM; P = 8.8 × 10⁻⁹). Ascaris spp. (19.27%) and Trichuris spp. (7.90%) predominated in low-income areas. Medium-income regions showed intermediate values, with notable regional variation.

CONCLUSIONS: Our results demonstrate that helminth egg diversity and concentration in sewage sludge are closely related to the socioeconomic characteristics of the served population. These findings may inform prevention and control strategies in vulnerable areas and support the development of public health and sanitation policies that address social and environmental inequalities in Brazil’s Central-Western region.

PMID:40500806 | DOI:10.1186/s40249-025-01314-8

BMC Glob Public Health. 2025 Jun 11;3(1):52. doi: 10.1186/s44263-025-00162-w.

ABSTRACT

BACKGROUND: During the early phase of the COVID-19 pandemic, the province of Ontario enacted restrictions and recommendations that changed over time. These measures were effective in reducing COVID-19-related illness and deaths, but adherence to these non-pharmaceutical interventions may be modified by individual factors including demographics and health status which shape exposure risk behaviors.

METHODS: A total of 348 participants completed baseline questionnaires (to assess demographics, pre-pandemic exposure risk, and health status), weekly illness reports, and monthly social distancing behavior questionnaires to evaluate exposure risk over time in response to changing levels of government restrictions. Exposure risk behaviors were calculated using seven categories: attendance at social events, receiving care (hospital, etc.), visiting or volunteering at care facilities, public transportation use, hours working outside of the home, hours volunteering outside of the home, and handwashing frequency. The impact of individual and environmental factors on exposure risk over time was evaluated by a Poisson family generalized linear mixed model.

RESULTS: Participants across all age groups and health statuses adapted their behaviors in response to evolving regulations, but older individuals and those with pre-existing conditions had the largest change in behavior. These individuals also had the most severe symptoms when they developed COVID-19 or other influenza-like illnesses. Participants who were older or had pre-existing health conditions had lower levels of exposure risk overall, and this was largely driven by a lower prevalence and frequency of in-person work. Female participants also had lower levels of exposure risk overall, consistent with an increased frequency of handwashing in this group. Unexpectedly, we found no effect of vaccination on total exposure risk.

CONCLUSIONS: Participant behavior was generally responsive to government-imposed restrictions, with increased stringency coinciding with decreased exposure risk among participants. Demographic-associated differences in exposure risk behaviors appear to be driven by systemic factors (i.e., a return to in-person work) to a greater extent than personal choices (i.e., social gatherings). These findings emphasize the interplay between demographic factors and government interventions in shaping individual behaviors over the course of the pandemic. Understanding these dynamics is crucial for informing interventions and mitigating the impact of future pandemics.

PMID:40500802 | DOI:10.1186/s44263-025-00162-w

Trop Med Health. 2025 Jun 11;53(1):79. doi: 10.1186/s41182-025-00737-1.

ABSTRACT

BACKGROUND: HIV remains one of the major global public health challenges, having claimed over 36 million lives so far, especially in sub-Saharan African countries like Nigeria. This study aimed to look into the trends in HIV-related knowledge, behavior and testing among young women in Nigeria.

METHODS: This study used data extracted from women aged 15-24 years who indicated that they had undergone HIV testing from the Nigeria Multiple Indicator Cluster Surveys (MICS) for 2007, 2011, and 2016. Across these surveys, similar sampling designs were applied, using a two-stage cluster sampling to generate a nationally representative sample of households. In the first stage, clusters were selected using the most recent available census from sampling frames. In the second stage, households were selected from each cluster. There was stratification of urban and rural for the different sampled clusters. The analysis was performed using STATA 17 software.

RESULTS: Northwest and South-South geopolitical zones, rural residential status and good knowledge about HIV were significantly associated with HIV testing. From 2011 to 2016, young women with primary education were significantly associated with reduced odds of HIV testing compared to those with at least secondary education. Young women with good behavior towards HIV prevention were significantly associated with higher odds of HIV testing, ranging from 1.7 times higher in 2011 to 1.8 times higher in 2016 compared with young women with poor behavior.

CONCLUSION: By prioritizing education, integrating HIV education and testing into school-based programs, and increasing access to healthcare services in rural areas, we can empower adolescents to make informed decisions about their health and reduce the spread of HIV.

PMID:40500790 | DOI:10.1186/s41182-025-00737-1

Arch Public Health. 2025 Jun 11;83(1):148. doi: 10.1186/s13690-025-01620-5.

ABSTRACT

OBJECTIVES: This study seeks to examine the impact of hospital organizational behavior on Physicians’ Patient-centered care and aims to offer innovative insights and strategies for enhancing the quality of healthcare services.

METHODS: A conceptual model was developed based on organizational behavior theory. Data were collected via questionnaires from 10 large public hospitals in China, encompassing eight independent variables, including hospital organizational culture, change behavior, and motivational behavior, as well as moderating variables like physician title and control variables such as personality traits. SPSS software was used for descriptive statistics, correlation analysis, covariance testing, and multiple linear regression analysis.

RESULTS: (1) The study of the 10 large public hospitals revealed a coexistence of four types of organizational cultures. Support-oriented and innovation-oriented cultures were dominant, followed by rule-oriented cultures, while goal-oriented cultures scored relatively low. Additionally, these hospitals showed effective organizational change behaviors in technology and resource optimization, as well as inter-professional teamwork. Incentives related to employee welfare systems and development programs also demonstrated high implementation effectiveness. (2) Supportive and innovation-oriented hospital cultures positively influence Physicians’ Patient-centered care, while goal-oriented cultures negatively impact Physicians’ Patient-centered care. (3) In public hospitals, organizational change behaviors such as technology and resource optimization, along with inter-professional teamwork, positively influence Physicians’ Patient-centered care. Additionally, organizational incentives like employee welfare systems and training programs enhance Physicians’ Patient-centered care. (4) The moderating variable of physician title negatively affects the relationship between the employee welfare system and Physicians’ Patient-centered care, as well as the relationship between the staff development program and Physicians’ Patient-centered care.

CONCLUSIONS: Hospital organizational behavior significantly impacts Physicians’ Patient-centered care. Supportive and innovative cultures, effective change behaviors, and incentives enhance Physicians’ Patient-centered care. Addressing limited resources and high demand is essential for optimizing healthcare service quality.

PMID:40500787 | DOI:10.1186/s13690-025-01620-5

Cost Eff Resour Alloc. 2025 Jun 11;23(1):28. doi: 10.1186/s12962-025-00635-7.

ABSTRACT

BACKGROUND: Idiopathic epilepsy is a serious neurological disorder that can lead to premature death and severe disability. We aimed to assess the global burden of idiopathic epilepsy, to provide a comprehensive understanding of the current dynamics and trends in idiopathic epilepsy, and to gain insight into its epidemiological attributes.

METHODS: This study assessed the global, regional, and national impact of idiopathic epilepsy through incidence and disability-adjusted life year (DALY) based on the Global Burden of Disease Study 2021 (GBD 2021). After statistically summarizing the global incidence rates and disability-adjusted life years (DALYs), we performed Estimating Average Percent Change (EAPC) correlation analyses and Joinpoint regression analyses to further derive global trends in idiopathic epilepsy incidence rates and DALYs. Furthermore, through decomposition analysis, we determined which factors significantly influence the change in incidence and DALYs and the extent of their contribution. In addition, this study quantified the disparities in the burden of idiopathic epilepsy across countries through cross-country social inequality analyses, and finally predicted the future burden of idiopathic epilepsy based on Bayesian Age-Period-Cohort Model (BAPC).

RESULTS: From 1990 to 2021, the incidence of idiopathic epilepsy increased generally, whereas DALY decreased. In terms of age and gender, the burden of idiopathic epilepsy is more severe in children and older age groups, with males bearing a higher burden than females. In terms of geographical distribution, the incidence was significantly higher in high Socio-Demographic Index (SDI) regions, while the burden of idiopathic epilepsy was heavier in low SDI areas. Decomposition analyses showed that the increase in incidence of idiopathic epilepsy and DALY in high SDI regions was mainly driven by epidemiological changes, whereas the increase in low SDI areas was more due to population growth. Cross-country social inequality analyses showed that despite improvements in the burden of idiopathic epilepsy, the burden and inequalities in low SDI countries remains significant. Projections indicated an increase in the incidence of idiopathic epilepsy globally, particularly in the 85 + age group, while global DALY was anticipated to continue declining.

CONCLUSIONS: Although global health is improving in line with population growth and age structure, the burden of idiopathic epilepsy remains significant. This study provides an important basis for prevention and care strategies for idiopathic epilepsy in different regions. Future work should focus on integrating idiopathic epilepsy into public health priorities, promoting effective measures, and narrowing treatment gaps.

PMID:40500766 | DOI:10.1186/s12962-025-00635-7

Genome Biol. 2025 Jun 11;26(1):161. doi: 10.1186/s13059-025-03635-1.

ABSTRACT

BACKGROUND: G-quadruplexes (G4s) are non-canonical DNA structures that can form at approximately 1% of the human genome. They facilitate genomic instability by increasing point mutations and structural variation. Numerous G4s participate in telomere maintenance and regulating transcription and replication, and evolve under purifying selection. Despite these important functions, G4s have remained under-studied in human and ape genomes due to incomplete assemblies.

RESULTS: Here, we conduct a comprehensive analysis of predicted G4s (pG4s) in the recently released, telomere-to-telomere (T2T) genomes of human, bonobo, chimpanzee, gorilla, Bornean orangutan, and Sumatran orangutan. We annotate 41,232-174,442 new pG4s in these T2T compared to previous ape genome assemblies (5%-21% increase). Analyzing inter-species whole-genome alignments, we identify pG4s shared across apes (approximately one-third of all pG4s) and thousands of species-specific pG4s. pG4s accumulate and diverge at rates consistent with divergence times between species, following molecular clock. pG4s shared across apes are enriched and hypomethylated at regulatory regions-enhancers, promoters, UTRs, and origins of replication-suggesting their conserved formation and functions. Species-specific pG4s (constituting 11-27% of all pG4s) are located in regulatory regions, potentially contributing to adaptations, and in repeats, likely driving genome expansions.

CONCLUSIONS: Our findings illuminate the evolutionary dynamics of G4s, conservation of their role in gene regulation, and their contributions to ape genome evolution. Our study highlights the utility of high-resolution T2T genomes in revealing elusive yet likely functionally relevant genomic features previously hidden by incomplete assemblies.

PMID:40500762 | DOI:10.1186/s13059-025-03635-1

Breast Cancer Res. 2025 Jun 11;27(1):102. doi: 10.1186/s13058-025-02062-1.

ABSTRACT

PURPOSE: Based on improved survival, the 2017 ASCO and Cancer Care Ontario clinical guidelines (ACGD) recommended consideration of adjuvant bisphosphonates for postmenopausal women with early-stage breast cancer (EBC). However, small survey-based studies suggest inconsistent prescribing. This study evaluated receipt of adjuvant bone modifying agents (BMAs) in the United States before and after publication of the 2017 ACGD.

METHODS: This nationwide retrospective cohort study used a deidentified electronic health record-derived database to identify patients diagnosed with stage I-III EBC treated at health care practices from 2012 to 2019. We defined adjuvant BMA (bisphosphonates or denosumab) use as first dose received within 24 months of EBC diagnosis. We used Chi-squared and multivariable logistic regression analyses to compare the proportion of patients receiving adjuvant BMAs pre- and post-ACGD and identify factors associated with receipt of any BMA as well as bisphosphonates alone.

RESULTS: Our cohort included 11,470 patients. Most patients were 50 years of age or older (82%), and had stage I (57%), node-negative (70%) and estrogen receptor (ER)-positive (76%) breast cancer. Patients diagnosed post-ACGD (2017-19) were more likely to receive adjuvant BMAs (9%) than patients diagnosed in earlier years (7.4%; odds ratio [OR] 1.23; 95% confidence interval (CI) 1.08-1.42; p = 0.002). Post-menopausal status, age ≥ 50, receipt of adjuvant chemotherapy and endocrine therapy, and coexisting bone loss diagnoses were significantly associated with increased receipt of adjuvant BMAs. Among BMA recipients, 65.8% received denosumab only, 32.6% received bisphosphonates only, and 1.4% received both.

CONCLUSIONS: Even after release of the ACGD guidelines, adjuvant BMA prescribing was low, and the majority of patients who received BMA did not receive bisphosphonates.

PMID:40500761 | DOI:10.1186/s13058-025-02062-1