Nevin Manimala

BMC Microbiol. 2025 Jun 26;25(1):371. doi: 10.1186/s12866-025-04106-0.

ABSTRACT

BACKGROUND: Dysbiosis, an imbalance in the bacterial composition of the human gut microbiota, is linked to inflammatory bowel disease (IBD). Advances in biological techniques have generated vast microbiota datasets, presenting both opportunities and challenges for clinical research in that field. Network theory offers powerful tools to analyze these complex datasets.

METHODS: Utilizing genetically unrelated individuals from the Kiel IBD-KC cohort, we compared network properties of the gut microbiota between patients with inflammatory bowel disease (IBD, n = 522) and healthy controls (n = 365), and between Crohn’s disease (CD, n = 230) and Ulcerative Colitis (UC, n = 280). Correlation-based microbial networks were constructed, with genera as nodes and significant pairwise correlations as edges. We used centrality measures to identify key microbial constituents, called hubs, and suggest a network-based definition for a core microbiota. Using Graphlet theoretical approaches, we analyzed network topology and individual node roles.

RESULTS: Global network properties differed between cases and controls, with controls showing a potentially more robust network structure characterized by e.g., a greater number of components and a lower edge density. Local network properties varied across all groups. For cases and both UC and CD, Faecalibacterium and Veillonella, and for unaffected controls Bacteroides, Blautia, Clostridium XIVa, and Clostridium XVIII emerged as unique hubs in the respective networks. Graphlet analysis revealed significant differences in terminal node orbits among all groups. Four genera which act as hubs in one state, were found to be terminal nodes in the opposite disease state: Bacteroides, Clostridium XIVa, Faecalibacterium, and Subdoligranulum. Comparing our network-based core microbiota definition with a conventional one showed an overlap in approximately half of the core taxa, while core taxa identified through our new definition maintained high abundance.

CONCLUSION: The network-based approach complements previous investigations of alteration of the human gut microbiota in IBD by offering a different perspective that extends beyond a focus solely on highly abundant taxa. Future studies should further investigate functional roles of hubs and terminal nodes as potential targets for interventions and preventions. Additionally, the advantages of the newly proposed network-based core microbiota definition, should be investigated more systematically.

PMID:40571931 | DOI:10.1186/s12866-025-04106-0

BMC Public Health. 2025 Jun 26;25(1):2176. doi: 10.1186/s12889-025-23578-3.

ABSTRACT

BACKGROUND: Academic performance in children is associated with a range of health-related factors, including physical fitness, mental well-being, sleep, and behavioral patterns. While previous studies have examined these factors individually, fewer have assessed their independent associations with academic achievement while accounting for other relevant health indicators. This study uses data from the I.Family study to explore how physical, mental, sleep-related, and behavioral health indicators relate to academic achievement among European adolescents, considering each factor’s contribution while adjusting for the others.

METHODS: We used data from the 2013-2014 wave of the I.Family study to investigate eight health indicators: health related quality of life (HRQoL), body mass index (BMI), diet, media use, physical activity, sleep duration and quality, and stressful life events. Their associations with self-reported academic performance in mathematics and language were analyzed using binary logistic regression models, adjusting for confounders such as parents’ education, income, survey country and child’s age. We conducted separate analyses for girls and boys to capture associations that are specific to academic subject and sex.

RESULTS: A number of significant associations were found between several health indicators and academic performance. Higher HRQoL scores, reduced media time, and increased physical activity were linked to better academic performance in both mathematics and language for both boys and girls. Variation by sex and academic subjects were observed, with lower BMI, higher healthy diet scores and better sleep quality associated with better academic performance in language among girls. For mathematics, emotional, self-esteem, and family-related HRQoL were all significantly associated with higher performance for both boys and girls. In contrast, for language achievement, only family-related HRQoL was significant for both sexes.

CONCLUSIONS: Our study underscores the need to consider both the importance of accounting for heterogeneity in sex and the differences between math and language academic subjects when investigating determinants of academic performance, setting the stage for further research on this topic to explore potential competing, synergistic, or time-dependent effects among these different health dimensions.

PMID:40571929 | DOI:10.1186/s12889-025-23578-3

Popul Health Metr. 2025 Jun 26;23(Suppl 2):31. doi: 10.1186/s12963-025-00389-7.

ABSTRACT

BACKGROUND: Measurement of excess mortality attributable to the COVID-19 pandemic is essential for quantifying the direct and indirect effects on mortality and informing future public health control strategies. This study assessed the impact of COVID-19 on excess mortality and life expectancy at birth in rural northern Ghana.

METHODS: Data was obtained from the Navrongo Health and Demographic Surveillance System (NHDSS) in Ghana. We computed the number of deaths and person-years contributed from January 1, 2015, to December 31, 2021, and estimated mortality rates for each year, age group, and gender. Mortality rate differences were calculated by comparing the period before (2018-2019) and during (2020-2021) the pandemic. To estimate excess mortality, a generalised additive model was fitted to the historical data from 2015 to 2019 to predict the expected mortality rates in the COVID-19 period (2020-2021). A Cox proportional hazards model was fitted to assess the risk factors associated with mortality, adjusting for socio-demographic variables. Conventional life table techniques were used to estimate period life expectancy at birth for males and females.

RESULTS: Overall, 12,413 deaths and 1,227,115 person-years were included in the analysis. This consists of 5,930 (49%) deaths and 572,963 person-years for the pre-pandemic period (2015-2019) and 6,483 (52%) deaths and 654,153 person-years for the pandemic period (2020-2021). From 2020 to 2021, the crude mortality rate was 23.9 deaths per 1000 person-years compared with 20.7 deaths per 1000 person-years predicted if COVID-19 had not occurred. COVID-19 also caused a decline in life expectancy at birth, especially in males, by 3.4 years. In addition, the adjusted risk of dying during the pandemic was higher in males (12.1%) compared to females and higher in the 65 + years age group (69.2%) compared to the younger population.

CONCLUSION: The COVID-19 pandemic caused an increase in deaths and a decrease in life expectancy in the NHDSS population in Ghana, particularly among men and those aged 65 years and older. These results reinforce the critical role of routine surveillance data in assessing the impact of public health emergencies such as the COVID-19 pandemic and informing public health strategies.

PMID:40571927 | DOI:10.1186/s12963-025-00389-7

BMC Public Health. 2025 Jun 26;25(1):2172. doi: 10.1186/s12889-025-23247-5.

ABSTRACT

BACKGROUND: Loneliness among children and adolescents has been increasingly recognized as a public health issue, for example, because of its associations with mental health problems. Nevertheless, there is a lack of evidence regarding the links between loneliness and mental health and the potential buffering role of social support. Thus, this study aims to investigate the prevalence of loneliness among children and adolescents in Germany and its associations with mental health. Furthermore, we analyze whether social support is negatively correlated with loneliness and mental health problems and whether it acts as a moderator of the association between loneliness and mental health issues.

METHODS: This study analyzed data from the Health Behavior in School-aged Children (HBSC) survey in Germany in 2022, which included 6,475 students aged 11, 13, and 15 years (girls: 50,6%, M_age = 13,4, SD = 1,7). Loneliness was measured via the University of California-Los Angeles Scale (UCLA) and a single-item measure. The mental health indicators included subjective health, life satisfaction, and multiple psychosomatic complaints. Social support from family, teachers, and classmates was assessed. Chi-square tests, t tests, logistic regressions, and moderation analyses were conducted.

RESULTS: A total of 17.2% of the students reported high levels of loneliness. Compared with boys, girls and gender-diverse students reported higher rates of loneliness. High levels of loneliness were strongly linked to poorer subjective health (OR = 5.56, p <.001), lower life satisfaction (OR = 7.32, p <.001), and increased psychosomatic complaints (OR = 7.38, p <.001). High social support from family, teachers, and students was associated with reduced loneliness and better mental health outcomes. Teacher support in grades 7 and 9 buffered the effect of loneliness on multiple psychosomatic complaints.

CONCLUSION: The findings highlight that loneliness is a prevalent phenomenon among children and adolescents and is strongly associated with mental health issues. Greater social support is linked to reduced loneliness and better mental health, so targeted interventions to promote social support in schools and families are needed to address loneliness. Future research should explore longitudinal relationships and further elucidate the mechanisms underlying these associations.

PMID:40571925 | DOI:10.1186/s12889-025-23247-5

Neurol Res Pract. 2025 Jun 26;7(1):45. doi: 10.1186/s42466-025-00399-8.

ABSTRACT

BACKGROUND: In the Find-AF 2 randomised controlled trial, we investigate whether a risk-adapted intensified heart rhythm monitoring with subsequent initiation of oral anticoagulation in ischaemic stroke patients leads to a reduction of recurrent ischaemic stroke and systemic embolism. The objective of this analysis is to present baseline characteristics of the overall Find-AF 2 study population and stratified by low or high risk for developing AF.

METHODS: The Find-AF 2 trial included acute ischaemic stroke patients ≥ 60 years of age within 30 days of ischaemic stroke of any cause. Before randomisation, patients received a 24-h Holter-ECG to exclude those with easily detectable AF and to determine the presence or absence of enhanced supraventricular ectopic activity (ESVEA), used as a marker indicating high or low risk for developing AF. Those without AF were randomly assigned 1:1 to either usual care diagnostics for AF detection (control group) or enhanced, prolonged and intensified ECG monitoring (intervention group). In the intervention group, patients with ESVEA received an implantable cardiac monitor (ICM), whereas those without ESVEA received repeated annual 7-day Holter ECGs. We present baseline characteristics of the overall Find-AF 2 population and stratified by ESVEA.

RESULTS: Between July 2020 and July 2024, 5227 patients (mean age 72.3 ± 7.5 years, 40% female, 2618 intervention group, 2609 control group) were randomised from 52 study centres in Germany within a median of 5 (IQR 3-7) days after the index stroke. The most frequent stroke aetiologies were cryptogenic (60%) and small vessel occlusion (19%). 1152 (22%) patients were at high risk for developing AF and 4075 (78%) at low risk. Patients within the high-risk stratum were significantly older (mean age 75.2 versus 71.5 years, p < 0.001), more often had moderate to severe stroke (34% versus 30%, p < 0.001), non-lacunar (70% versus 64%, p < 0.001) and of cryptogenic aetiology (64% vs 58%, p < 0.001).

CONCLUSIONS: The Find-AF 2 trial has successfully completed recruitment of a large acute ischaemic stroke population with different stroke subtypes. The follow-up is ongoing and results are expected within two years.

TRIAL REGISTRATION: ClinicalTrials.gov, Identifier NCT04371055, registered 24 April 2020.

PMID:40571918 | DOI:10.1186/s42466-025-00399-8

BMC Public Health. 2025 Jun 26;25(1):2175. doi: 10.1186/s12889-025-23539-w.

ABSTRACT

BACKGROUND: Although mental well-being is facing growing challenges against the background of global crises such as climate change, pandemics, and social inequality, little is known about longitudinal patterns of mental well-being in the general population.

METHODS: The study is based on self-report data from 1,605 adults aged 18 to 64 years who were proactively recruited at a municipal registration office (M = 31.0 years, SD = 10.8 years). Mental well-being was assessed at baseline, and 3, 6, 12, 36 and 48 months later using the five-item Mental Health Inventory (MHI-5). Covariates were smoking, alcohol consumption, fruit and vegetable intake, moderate-to-vigorous physical activity, age, sex, school education and relationship status. Growth Mixture Modeling was used to identify latent trajectory classes of mental well-being. Multinomial logistic regression was used to test whether class membership is predicted by health behaviors and sociodemographic variables.

RESULTS: Three latent trajectory classes were found. The first class (“stable high”, n = 1,251, 78%) showed the highest mental well-being throughout the study with only minor fluctuations over time. The second class (n = 192, 12%) showed a “steadily increasing” trajectory starting with the lowest MHI-5 sum score of the three classes at baseline that increased over time. The third class (“fluctuating”, n = 162, 10%) reported a slight increase in mental well-being during the first six months, followed by a steep decline to 36 months, which then increased to almost baseline-level at 48 months. The odds of being classified into the “steadily increasing” or “fluctuating” compared to the “stable high” class were higher for men and younger participants. The odds of belonging to the “steadily increasing” compared to the “stable high” class were higher for participants with more than 12 years of school education and those being in a relationship. Health behaviors did not predict latent trajectory class membership.

CONCLUSION: Three different temporal patterns of mental well-being were found in a German general population sample, with the majority showing a stable level of high mental well-being over four years. Further research is needed to understand fluctuating patterns and the causal factors influencing mental well-being.

PMID:40571917 | DOI:10.1186/s12889-025-23539-w

Interdiscip Sci. 2025 Jun 26. doi: 10.1007/s12539-025-00728-0. Online ahead of print.

ABSTRACT

Recent advancements in spatial transcriptomics (ST) technologies have greatly revolutionized our understanding of tissue heterogeneity and cellular functions. However, popular ST, such as 10x Visium, still fall short in achieving true single-cell resolution, underscoring an urgent need for in-silico methods that can accurately resolve cell type composition within ST data. While several methods have been proposed, most rely solely on gene expression profiles, often neglecting spatial context, which results in suboptimal performance. Additionally, many deconvolution methods dependent on scRNA-seq data fail to align the distribution of ST and scRNA-seq reference data, consequently affecting the accuracy of cell type mapping. In this study, we propose stGNN, a novel spatially-informed graph learning framework powered by statistical modeling for resolving fine-grained cell type compositions in ST. To capture comprehensive features, we develop a dual encoding module, utilizing both a graph convolutional network (GCN) and an auto-encoder to learn spatial and non-spatial representations respectively. Following that, we further design an adaptive attention mechanism to integrate these representations layer-by-layer, capturing multi-scale spatial structures from low to high order and thus improving representation learning. Additionally, for model training, we adopt a negative log-likelihood loss function that aligns the distribution of ST data with scRNA-seq (or snRNA-seq) reference data, enhancing the accuracy of cell type proportion prediction in ST. To assess the performance of stGNN, we applied our proposed model to six ST datasets from various platforms, including 10x Visium, Slide-seqV2, and Visium HD, for cell type proportion estimation. Our results demonstrate that stGNN consistently outperforms seven state-of-the-art methods. Notably, when applied to mouse brain tissues, stGNN successfully resolves clear cortical layers at a high resolution. Additionally, we show that stGNN is able to effectively resolve ST at different resolutions. In summary, stGNN provides a powerful framework for analyzing the spatial distribution of diverse cell populations in complex tissue structures. stGNN’s code is openly shared on https://github.com/LiangSDNULab/stGNN .

PMID:40571903 | DOI:10.1007/s12539-025-00728-0

Paediatr Drugs. 2025 Jun 26. doi: 10.1007/s40272-025-00702-9. Online ahead of print.

ABSTRACT

BACKGROUND AND OBJECTIVES: Ustekinumab (USTE) and vedolizumab (VEDO) are increasingly used in paediatric patients with inflammatory bowel diseases (pIBD). However, data on the usefulness of therapeutic drug monitoring (TDM) in children are scarce. The primary objective of this study was to evaluate the association between disease activity, measured by faecal calprotectin (F-CPT), and serum trough levels (TLs) of USTE and VEDO. Secondary outcomes were to explore factors potentially associated with the outcome and exposure, to determine the optimal USTE or VEDO dose that predicts remission (defined as F-CPT < 250 µg/g), to validate our hypothesis using a proof-of-concept cohort (POCC) and to assess the occurrence of serum antibodies to USTE and VEDO.

METHODS: This was a prospective single-centre observational study performed at the University Hospital Motol, Prague, Czech Republic. Of the 87 patients (51 Crohn’s disease (CD), 30 ulcerative colitis (UC), and 6 IBD unclassified (IBD-U)), drug serum TLs and antibodies were measured in 282 observations (49 treatment courses) of USTE and 359 observations (38 courses) of VEDO. Serum and stool samples were collected before each study drug application during both the induction and maintenance phases of the treatment throughout the entire study period (January 2020 to June 2024). Clinical and laboratory data were obtained from the nationwide prospective registry CREdIT. Patients with perianal disease and those with previous major bowel surgery were not excluded from the study. As a POCC, we analysed a group of pIBD treated at our centre with anti-TNF agents-adalimumab or infliximab.

RESULTS: In a linear multiple regression mixed model, an association was observed between logF-CPT levels and USTE treatment duration (β -0.0010, 95% confidence interval (CI) -0.0015 to -0.0006, p < 0.001) but not with USTE TLs (p = 0.12). VEDO TLs and logF-CPT levels were negatively associated both in the linear (β -0.0173, 95% CI -0.0292 to -0.0053, p = 0.005) and categorical models (p = 0.026), even after adjusting for time. A VEDO TL of 15.1 µg/mL showed the best, though still poor, combination of sensitivity (0.82) and specificity (0.32) to predict F-CPT < 250 µg/g (area under the curve (AUC) 0.56, 95% CI 0.49-0.63). Intensification, induction phase, undetectable TLs, and type of IBD (CD, UC, IBD-U) were not associated with logF-CPT. Slightly elevated anti-drug antibodies were detected in 5 USTE and 16 VEDO observations, with no clinical implications.

CONCLUSIONS: TDM of USTE does not appear to be useful in pIBD. TDM of VEDO may assist in therapeutic strategy decisions, although establishing clinically useful cut-offs remains challenging.

PMID:40571898 | DOI:10.1007/s40272-025-00702-9

Drugs. 2025 Jun 26. doi: 10.1007/s40265-025-02205-w. Online ahead of print.

ABSTRACT

BACKGROUND: Plecanatide is a novel guanylate cyclase-C agonist for the treatment of functional constipation (FC). Its efficacy may vary across different racial populations.

OBJECTIVE: This study aimed to comprehensively evaluate the efficacy, safety, and pharmacokinetics of plecanatide in Chinese patients with FC.

METHODS: This phase III, randomized, double-blind, placebo-controlled trial was conducted across 40 hospitals in China. A total of 648 patients with FC were randomly assigned in a ratio of 1:1 to receive either plecanatide 3 mg or placebo for 12 weeks, followed by a 2-week follow-up. The primary efficacy endpoint was the durable overall complete spontaneous bowel movement (CSBM) response rate. Data on adverse events were collected. A post hoc logistic regression analysis was performed to identify predictors of durable overall CSBM response.

RESULTS: After 12 weeks of continuous treatment, the durable overall CSBM response rates were 23.5% in the plecanatide group and 10.2% in the placebo group (p < 0.001). Plecanatide significantly increased the mean weekly frequency of CSBM (1.89 vs 0.9) and SBM (2.33 vs 1.03) compared with placebo throughout the treatment period. In addition, all other secondary efficacy endpoints showed statistically significant improvements with plecanatide compared with placebo. The most common treatment-related emergent adverse event was diarrhea, which occurred in 4.3% of plecanatide-treated patients and 0.6% of placebo-treated patients (p = 0.002). Plasma concentrations of plecanatide and its metabolite SP-338 remained below the lower limit of quantification (0.500 ng/ml) at all assessed time points. Weekly CSBM response at week 2 (odds ratio 43.476; 95% confidence interval 18.274-103.432) and baseline stool consistency (odds ratio 0.550; 95% confidence interval 0.366-0.827) were identified as effective predictors of durable overall CSBM response. Even among plecanatide non-responders, a significant improvement in SBM frequency compared with placebo was observed over the 12-week treatment period.

CONCLUSIONS: Plecanatide 3 mg was effective and well tolerated in the treatment of Chinese patients with FC. A weekly CSBM response at week 2 may serve as a predictor of 12-week durable overall efficacy. Patients who did not achieve the primary endpoint may still benefit from plecanatide treatment.

CLINICALTRIALS: GOV: NCT0515132.

PMID:40571893 | DOI:10.1007/s40265-025-02205-w

J Appl Res Intellect Disabil. 2025 Jul;38(4):e70089. doi: 10.1111/jar.70089.

ABSTRACT

BACKGROUND: To date, no studies have examined the prevalence of hoarding behaviour and domestic squalor among individuals with mild intellectual disability. To address this gap, we conducted a prevalence study within a population supported by a medium-sized care organisation in the Netherlands.

METHOD: Data were collected on 437 individuals with mild intellectual disability receiving care in residential facilities or through outpatient services. Assessments were conducted using the Hoarding Rating Scale-Interview, the Environmental Cleanliness and Clutter Scale, and the Clutter Image Rating Scale.

RESULTS: Hoarding behaviour and/or domestic squalor were observed in 16.8% of the residents. Support staff identified 8.3% of dwellings as posing significant safety risks or health hazards. Additionally, 6.7% of residents had been threatened with eviction due to hoarding or squalor.

CONCLUSIONS: Hoarding behaviour and domestic squalor appear to be more prevalent among individuals with mild intellectual disability in care settings than among the overall population.

PMID:40571875 | DOI:10.1111/jar.70089