BMC Medicine[JOURNAL]
Sun
200 papers
Dementia risk by metabolic health and obesity in two prospective cohorts.
Nakash M, Ojalehto Lindfors E, Zhan Y … +4 more , Dahl Aslan AK, Reynolds CA, Ler P, Karlsson IK
BMC Med · 2026 Jun · PMID 42321773 · Full text
BACKGROUND: Midlife obesity is a well-established risk factor for dementia, whereas late-life obesity has been associated with no increased risk, or even a reduced risk in some studies. However, the joint associations of...
BACKGROUND: Midlife obesity is a well-established risk factor for dementia, whereas late-life obesity has been associated with no increased risk, or even a reduced risk in some studies. However, the joint associations of obesity (body mass index ≥ 30 kg/m) and metabolic health phenotypes (defined by the presence of hyperglycemia, hypertension and dyslipidemia) with dementia risk are less explored, particularly with regard to age- and sex-related differences. Therefore, we investigated how obesity and metabolic health phenotypes jointly associate with dementia risk and whether this risk differs between midlife (≤ 65 years) and late-life (> 65 years), and sex. METHODS: We analysed data from 11,482 participants, aged 51 to 100 years, from the US Health and Retirement Study (HRS), and 13,068 participants, aged 45 to 90 years, from the Swedish Twin Registry (STR). Cox regression models were used to estimate dementia risk in relation to metabolically healthy obesity (MHO), metabolically unhealthy obesity (MUO), and metabolically unhealthy no obesity (MUNO), relative to metabolically healthy no obesity (reference). Models were adjusted for age, sex, smoking status, and education level. Analyses were stratified by midlife and late-life and conducted in the entire sample and separately by sex. RESULTS: Metabolically unhealthy status in midlife and late-life indicated increased dementia risk regardless of obesity status, reaching statistical significance for midlife MUNO in females in HRS (Hazard ratio (HR): 1.62, 95% confidence intervals (CI): 1.05-2.49) and in late-life MUNO for the full sample in STR (HR: 1.13, CI: 1.02-1.25) and males in the STR (HR: 1.22, CI: 1.04-1.42). The associations between MUO and dementia risk were not statistically significant, but trends suggested midlife MUO was associated with higher dementia risk. The associations between mid and late-life MHO with dementia risk were also not statistically significant, although the associations showed trends towards lower dementia risk. CONCLUSIONS: Being metabolically unhealthy, especially in midlife, may be associated with increased dementia risk, regardless of obesity status. Mid- and late-life MHO showed no increased risk and suggested potential inverse associations. These findings underscore the importance of evaluating dementia risk in the context of obesity, metabolic health, age and sex simultaneously.
Outcome measurement for multiple long-term conditions research across health-care settings - an overview of reviews.
O'Mahoney LL, Peace A, Gillies CL … +12 more , Routen A, Highton PJ, Bedford P, Abdala R, Sathanapally H, Chudasama YV, Patel R, Perera R, Hughes SE, Walker H, Funnell MP, Khunti K
BMC Med · 2026 Jun · PMID 42321748 · Full text
BACKGROUND: Multiple long-term conditions (MLTC) represent a growing global public health challenge, yet research is hindered by inconsistent outcomes across health-care settings and populations. Although several core ou...
BACKGROUND: Multiple long-term conditions (MLTC) represent a growing global public health challenge, yet research is hindered by inconsistent outcomes across health-care settings and populations. Although several core outcome sets (COS) have been developed, important gaps remain in their coverage, inclusivity, and measurement validity. This overview of reviews summarised outcomes reported in systematic reviews of MLTC research to identify existing domains, describe how measurement instruments were addressed, and highlight areas requiring standardisation. METHODS: We conducted a prospectively registered overview of reviews (PROSPERO CRD420251005152), following PRISMA, PRIOR, and SWiM guidelines. Eligible reviews included adults or children with MLTC-defined as the coexistence of two or more chronic conditions-and reported on outcome measures or COS relevant to this population. Five databases (MEDLINE, CINAHL, Scopus, Cochrane Library, COMET (Core Outcome Measures in Effectiveness Trials)) were searched from inception to April 2025. Two reviewers independently screened, extracted data, and appraised quality using the Joanna Briggs Institute checklist. A narrative synthesis mapped outcomes by domain (clinical, patient-reported, service/system, engagement/experience), care setting, and population subgroup. RESULTS: From 6331 records, 10 reviews met inclusion criteria, encompassing 709 primary studies. Four developed COS, and six mapped outcomes without proposing COS. Quality of life and health-care utilisation were most consistently reported; treatment burden, patient engagement, and child outcomes were infrequently assessed. Existing COS advanced standardisation but remained limited in stakeholder diversity, geographic scope, and specification of measurement instruments, with only one including low- and middle-income countries. CONCLUSIONS: Greater inclusivity, validation, and global applicability are needed to operationalise agreed domains and improve comparability across MLTC research.
Non-linear age dynamics of malaria infection and fine-scale environmental exposure in rural Uganda.
Lang MM, Tuhaise V, Kafuko P … +6 more , Nakato A, Mohamed A, Nabatte B, Kabatereine NB, Donnelly CA, Chami GF
BMC Med · 2026 Jun · PMID 42316253 · Full text
BACKGROUND: Age-specific patterns of malaria are well-established for children aged < 5 years. Less understood is the epidemiology of malaria in older children and adults, and the influence of granular environmental ris...
BACKGROUND: Age-specific patterns of malaria are well-established for children aged < 5 years. Less understood is the epidemiology of malaria in older children and adults, and the influence of granular environmental risk. METHODS: We analyzed data from SchistoTrack, a community-based cohort in rural Uganda. We studied 4308 participants aged 5 to 90 years from 52 villages across three lakeside districts of Mayuge, Buliisa, and Pakwach, with enrollment between January 2022 to February 2024. The primary outcome was malaria infection status by rapid diagnostic test (RDT). Secondary outcomes included microscopy-confirmed infection with parasite density quantification and self-reported fever within the past month. We fitted a generalized additive mixed model (GAMM) with adaptive age smoothing, adjusting for sociodemographic factors, household characteristics, healthcare access, and environmental exposures. Environmental exposure was quantified using the Normalized Difference Vegetation Index (NDVI) derived from Sentinel-2 satellite imagery (10 m resolution), processed through hexagonal aggregation with Gaussian neighborhood smoothing and validated against field malacology surveys and participatory community mapping. RESULTS: Overall RDT prevalence was 41.2% (1776/4308), with microscopy prevalence at 32.3% (1363/4219), which was predominantly Plasmodium falciparum (83.1%; 1133/1363). Most infections were low-density ( < 999 parasites/μL; 71.6%; 976/1363). Malaria prevalence showed non-linear age patterns, peaking at 10 to 11 years then declining through adolescence before stabilizing in adulthood. Among RDT-positive individuals, fever prevalence decreased with age from 30.8% in children (aged 5 to 10 years) to 11.2% in adults (aged ≥20 years). Dense vegetation (per unit NDVI increase: Odds Ratio (OR) 3.25, 95% Confidence Interval (CI) 1.33-7.96) and greater distance from government health centers (per log-km: OR 1.87, 95% CI 1.34-2.59) increased the odds of infection. Proximity to vegetated water bodies increased the odds of infection compared to beaches: ponds/swamps (OR 1.65, 95% CI 1.19-2.28), river/river marsh (OR 1.63, 95% CI 1.16-2.31), lake marsh (OR 1.40, 95% CI 1.07-1.83). CONCLUSIONS: Malaria prevalence remains high in older children and adults, though with fewer febrile cases, and is influenced by the local environment. Our findings support age-specific interventions targeting school-aged children while maintaining adult surveillance, and using validated environmental indices to guide sub-district resource allocation in high-risk areas.
Daily alcohol consumption trajectories and user retention during a national temporary abstinence campaign: real-world data from a smartphone application.
Naassila M, Simon N, André J … +6 more , Dreinaza M, Trouillet R, Benyamina A, Basset B, Grellet L, Perney P
BMC Med · 2026 Jun · PMID 42316182 · Full text
BACKGROUND: Temporary Abstinence Challenges (TAC), such as Dry January, are widely implemented public health initiatives and have been associated with short- and medium-term reductions in alcohol consumption. Smartphone...
BACKGROUND: Temporary Abstinence Challenges (TAC), such as Dry January, are widely implemented public health initiatives and have been associated with short- and medium-term reductions in alcohol consumption. Smartphone applications are increasingly recommended to support participation, yet little is known about real-world user engagement and day-to-day drinking trajectories during these campaigns. This study examined patterns of app use, retention, and alcohol consumption among users of a smartphone application during the 2024 national "Défi de janvier" campaign in France. METHODS: We conducted an observational analysis of anonymized, app-based self-reported data collected between 1 and 31 January 2024. Daily alcohol consumption and engagement were analyzed among 2,032 adult users according to age, sex, and baseline World Health Organization (WHO) drinking-risk level assessed during a reference week preceding the campaign. User retention was examined using Cox proportional hazards models, and changes in alcohol consumption were analyzed using daily trajectories and linear mixed-effects models. RESULTS: Higher baseline WHO drinking-risk levels and younger age were independently associated with lower retention, whereas sex and binge drinking during the reference week were not. Across all drinking-risk groups of users who remained engaged, alcohol consumption followed a stable weekly pattern with peaks on Fridays and Saturdays. Among users with available data over time, mean self-reported daily alcohol consumption decreased over January across baseline risk categories. Absolute reductions were greatest among users with higher baseline consumption, while individuals with lower-risk drinking showed smaller but consistent decreases. CONCLUSIONS: In this large real-world sample of smartphone application users participating in a national temporary abstinence challenge, alcohol consumption declined among users who remained engaged and across all baseline drinking-risk levels, despite substantial variability in user retention. These findings provide real-world evidence on engagement patterns and self-reported drinking trajectories among users of a digital tool during a national Temporary Abstinence Challenge, and highlight opportunities to optimize future interventions, particularly for younger users and those with higher baseline drinking levels.
Association between caesarean birth and childhood acute respiratory infection in low- and middle-income countries: a meta-analysis of population-based data.
Mare KU, Yisma E, Lassi ZS
BMC Med · 2026 Jun · PMID 42310734 · Full text
BACKGROUND: Caesarean section (CS) rates are rising across low- and middle-income countries (LMICs), frequently exceeding levels considered medically necessary. While CS can be lifesaving, emerging evidence from high-inc...
BACKGROUND: Caesarean section (CS) rates are rising across low- and middle-income countries (LMICs), frequently exceeding levels considered medically necessary. While CS can be lifesaving, emerging evidence from high-income settings suggests that delivery by CS may increase children's susceptibility to respiratory infections. However, population-based evidence from LMICs remains limited. We investigated the association between mode of delivery and acute respiratory infection (ARI) among children younger than five years across diverse LMIC settings. METHODS: We analysed nationally representative Demographic and Health Surveys data from 47 LMICs collected between 2015 and 2024, including 534,423 singleton live births. Mode of delivery (caesarean section vs. vaginal birth) was the exposure. ARI was defined as maternal report of cough with rapid or difficult breathing in the preceding two weeks before each survey. Country-specific adjusted prevalence ratios (aPRs) were estimated using modified Poisson regression models accounting for sociodemographic, maternal, perinatal, and environmental factors. Country-specific estimates were then pooled using random-effects meta-analysis, including subgroup analyses by national income level and caesarean section rate. RESULTS: The prevalence of caesarean section ranged from 1.3% in Chad to 44.9% in Bangladesh. The prevalence of ARI ranged from < 1% in Mozambique, Cote d'Ivoire, the Philippines, and the Maldives to 14% in Pakistan. In pooled analyses, children born by caesarean section had a higher prevalence of ARI than those born vaginally (pooled aPR 1.11; 95% CI 1.02-1.20), with low between-country heterogeneity (I² = 9.62%). The association was stronger in low- and lower-middle-income countries and in countries with very low caesarean section rates (< 10%), where caesarean birth was associated with a 17% higher prevalence of ARI. CONCLUSIONS: Across 47 LMICs, caesarean birth was associated with a modestly higher prevalence of acute respiratory infection in children younger than five years. While this finding is consistent with existing evidence, it should be interpreted with caution given the potential for residual confounding, including confounding by indication. These findings highlight the importance of reducing non-medically indicated caesarean sections while ensuring access to life-saving obstetric care. Strengthening evidence-based decision-making around mode of delivery may contribute to reducing preventable childhood respiratory morbidity in resource-limited settings.
Diagrams-to-Dynamics (D2D): Exploring causal loop diagram leverage points under uncertainty.
Uleman JF, Crielaard L, Elsenburg LK … +4 more , Veldhuis GA, Rod NH, Quax R, Vasconcelos VV
BMC Med · 2026 Jun · PMID 42310733 · Full text
BACKGROUND: Causal loop diagrams (CLDs) are widely used in health and environmental research to represent hypothesized causal structures underlying complex problems. However, as qualitative and static representations, CL...
BACKGROUND: Causal loop diagrams (CLDs) are widely used in health and environmental research to represent hypothesized causal structures underlying complex problems. However, as qualitative and static representations, CLDs are limited in their ability to support dynamic analysis and inform intervention strategies. We propose Diagrams-to-Dynamics (D2D), a method for converting CLDs into exploratory system dynamics models in the absence of empirical data. With minimal user input-following a protocol to label variables as stocks, flows or auxiliaries, and constants-D2D utilizes the structural information already encoded in CLDs, namely the existence and polarity of causal connections, to simulate hypothetical interventions and explore potentially influential places to intervene, known as 'leverage points,' under uncertainty. RESULTS: D2D helps distinguish between high- and low-ranked leverage points. We compare D2D to a calibrated system dynamics model constructed from the same CLD and variable labels. D2D showed greater consistency with the calibrated model than did static network centrality analysis, while also providing uncertainty estimates and guidance for future data collection. CONCLUSIONS: The D2D method is implemented in a Python package and a web-based application to support further testing and to lower the barrier to dynamic modeling for researchers working with CLDs. Future studies could help establish the approach's utility across a broad range of cases and domains.
Effectiveness of bullying prevention-associated interventions among children and adolescents: an umbrella review of systematic review and meta-analysis.
Li ZW, Lu L, Qin XD … +6 more , Li R, Zhou Z, Liu S, Liu Q, Lai S, Shen Q
BMC Med · 2026 Jun · PMID 42310730 · Full text
BACKGROUND: Bullying represents a critical global health concern among children and adolescents, emphasizing an urgent need for effective prevention interventions. Current meta-analyses frequently focus on single prevent...
BACKGROUND: Bullying represents a critical global health concern among children and adolescents, emphasizing an urgent need for effective prevention interventions. Current meta-analyses frequently focus on single prevention interventions or outcomes, limiting the generalizability of findings for cross-intervention comparisons. We aimed to perform an umbrella review to provide an overview of the effectiveness of bullying prevention interventions. METHODS: Potential literature was searched from PubMed, Web of Science, Embase, and EBSCO from their respective inception to October 22, 2024. Three reviewers independently selected meta-analysis of bullying prevention intervention that reported any type of prevention intervention and assessed outcomes in children and adolescents. Following PRISMA guidelines, three reviewers independently extracted data and evaluated study quality using AMSTAR-2. All effect estimates were converted to Cohen's d for cross-domain comparisons. RESULTS: 4740 studies were identified with 30 meta-analyses included. Studies reporting statistical significance all demonstrated beneficial effects of bullying prevention interventions. Included meta-analyses evaluated 17 distinct prevention interventions in alleviating bullying via assessment on three main outcomes with 49 distinct sub-outcomes, i.e., behavior change (36 sub-outcomes, the most frequent target), mental health (9 sub-outcomes), and attitude change (4 sub-outcomes). 30 studies were categorized into five categories based on the leading role of prevention interventions: family-based (n = 2), school-based (n = 10), community-based (n = 2), healthcare-based (n = 5), and collaborative (n = 11). Cohen's d values ranged from -0.99 to 1.14, with the music-based intervention exhibiting the largest observed point estimate (Cohen's d = -0.99, 95% confidence interval [CI]: -1.42 to -0.56), which was also the largest among interventions targeting behavior change. Martial arts presented largest observed point estimate among collaborative prevention interventions, while digital health intervention, anti-aggression program, and parent-related intervention showed the largest observed point estimates among community-based, school-based, and family-based prevention interventions, respectively. For mental health, sports intervention exhibited the largest observed point estimate. And for attitude change, anti-bullying intervention presented the largest estimate, consistent with results from RCT-only subgroup. CONCLUSIONS: Bullying prevention interventions may be associated with improvements in positive behavior change, attitude change, and mental health, with substantial variations in effectiveness. These findings regarding comparative efficacy may inform the strategic selection of preventive interventions in future evaluation and implementation efforts. PROSPERO REGISTRATION NUMBER: CRD42024601712.
NMR-based serum metabolite and lipoprotein profiling for endometriosis across clinically relevant and physiological comparator settings: assessment of diagnostic utility and exploratory biological signals.
Deng S, Koch A, Krämer B … +9 more , Cannet C, Singh Y, Bae G, Sklut J, Reinsperger T, Millet O, Andress J, Schimunek L, Trautwein C
BMC Med · 2026 Jun · PMID 42310722 · Full text
BACKGROUND: Reliable non-invasive biomarkers for endometriosis remain unavailable in routine practice, and their translational value depends on performance in symptomatic referral populations rather than only against hea...
BACKGROUND: Reliable non-invasive biomarkers for endometriosis remain unavailable in routine practice, and their translational value depends on performance in symptomatic referral populations rather than only against healthy controls. We evaluated Nuclear Magnetic Resonance (NMR)-based serum metabolite and lipoprotein profiling for endometriosis across clinically relevant and physiological comparator settings, alongside exploratory analyses of systemic biological variation. METHODS: Blood serum samples from women with surgically confirmed endometriosis, symptomatic controls, and healthy volunteers underwent quantitative in vitro diagnostics research (IVDr) H-NMR-based metabolite and lipoprotein profiling. A subset also underwent cytokine profiling. Two diagnostic settings were prespecified: endometriosis versus symptomatic controls (primary) and endometriosis versus healthy volunteers (secondary). Baseline models included age and body mass index, while full models incorporated the IVDr metabolite-lipoprotein panel using elastic net regularization. Performance was assessed using fully nested repeated cross-validation and an independently processed temporal cohort. Exploratory analyses included covariate-adjusted group comparisons, weighted correlation network analysis, cytokine correlations, and paired pre-/post-operative comparisons. RESULTS: In the primary symptomatic-control comparison, the IVDr panel did not improve diagnostic performance beyond age and body mass index (AUC 0.620 vs. 0.637 for baseline). Discrimination was substantially higher in the healthy-volunteer comparison (AUC 0.994 for the full model vs. 0.882 for baseline), but this pattern was not reproduced in the temporal cohort, where performance was poor in both comparator settings. Exploratory analyses showed that the clearest biological differences were concentrated in healthy-based contrasts, with lower amino acids, creatinine, lactic acid, and selected low-density lipoprotein (LDL) measures in endometriosis. Part of the amino-acid pattern was also present in symptomatic controls, whereas particularly LDL6 lipoprotein subfractions, appeared more restricted and were supported by lipoprotein-enriched network structure. Cytokine-cytokine correlations showed reproducible within-panel immune covariance, but no cross-domain correlations remained significant after false discovery rate correction. CONCLUSIONS: While NMR-based serum metabolite and lipoprotein profiling showed strong apparent discrimination against healthy volunteers, performance was limited in the clinically relevant symptomatic-control setting, underscoring the importance of comparator spectrum for translational biomarker evaluation. Exploratory analyses identified biologically informative serum patterns, particularly a more restricted lipoprotein-subclass LDL6 signal that warrants targeted replication in clinically representative and analytically harmonized studies.
Changes in olfactory function in children and adolescents with obesity following an inpatient weight loss program: a longitudinal study.
Klos B, Sauer H, Steinhauser V … +6 more , Godwin J, Ohla K, Schriever VA, Zipfel S, Enck P, Mack I
BMC Med · 2026 Jun · PMID 42310628 · Full text
BACKGROUND: Obesity is a major global public health burden, yet the mechanisms underlying interindividual variability in treatment response remain poorly understood. Olfactory function influences eating behavior and may...
BACKGROUND: Obesity is a major global public health burden, yet the mechanisms underlying interindividual variability in treatment response remain poorly understood. Olfactory function influences eating behavior and may differ in individuals with obesity. However, evidence in pediatric populations is limited, and their responsiveness to weight loss remains unclear. This study aimed to assess olfactory function in children and adolescents with obesity before and after an inpatient weight loss intervention. Specifically, we examined whether olfactory performance is within normative values and whether it changes in response to weight reduction. METHODS: Sixty children and adolescents with overweight or obesity (13.0 ± 1.9 years, BMI z-score: 2.5 ± 0.5) underwent a structured inpatient rehabilitation program (mean duration: 38 ± 10 days) integrating nutrition therapy, physical activity, stress management, and behavioral modification. Olfactory function was assessed at baseline (T1, ~ 7 days after admission) and after the intervention (T2, ~ 27 days after T1) using the Sniffin' Sticks Test©, comprising odor threshold, discrimination, and identification. At both time points, participants self-reported their perceived olfactory ability. RESULTS: At T1, data were available for 59 participants; 50 completed the follow-up assessment at T2. Completers showed significant reductions in body weight and BMI z-score (p < .001). Olfactory function at T1 was largely within the normative range when compared with age-matched reference data. During weight loss, olfactory function remained largely stable: odor identification improved modestly (p = .003), whereas odor threshold and discrimination showed no significant changes and were not associated with weight loss. Self-reported olfactory ability showed weak correspondence with objective measures and remained unchanged. CONCLUSIONS: Olfactory function in children and adolescents with obesity was largely within the normative range and showed limited change during short-term inpatient weight loss. These findings suggest that olfactory alterations may not be a primary determinant of short-term treatment response. However, age- and domain-specific variability may still be relevant for how individuals perceive and respond to food-related cues, with potential implications for dietary adherence and long-term weight management. Future studies with normal-weight control groups should examine whether such variability contributes to differences in eating behavior and long-term outcomes. TRIAL REGISTRATION: DRKS00005122.
Long-term metabolically unhealthy aging, its underlying molecular underpinnings, and association with cognitive impairment: a 12.4-year longitudinal cohort study.
Deng K, Zhang Z, Zhang K … +12 more , Zhou K, Wang X, Jia S, Ru D, Lu Z, Yan Y, Huang F, Chen T, Zheng JS, Xie G, Huang Y, Chen YM
BMC Med · 2026 Jun · PMID 42304453 · Full text
BACKGROUND: Individuals experience heterogeneous aging processes closely associated with metabolism. However, it remains unclear whether older adults undergo different metabolic health-related aging patterns over time. W...
BACKGROUND: Individuals experience heterogeneous aging processes closely associated with metabolism. However, it remains unclear whether older adults undergo different metabolic health-related aging patterns over time. We aimed to investigate the long-term metabolic health-related aging trajectories, their associations with cognitive function, and underlying molecular underpinnings among older adults. METHODS: This study was based on a longitudinal cohort of 1334 middle-aged and elderly Chinese adults (age: 57.5 ± 5.2 years; 30.7% men) with a median follow-up of 12.4 years across four visits. We used the latent class growth mixed model to identify longitudinal metabolic disturbance trajectory groups. We then examined the prospective associations of the identified longitudinal metabolic disturbance subtypes with cognitive function assessed by Addenbrooke's Cognitive Examination-Revised (ACE-R), and with brain structure measured by magnetic resonance imaging. Leveraging repeated-measured proteome (up to three times; N = 1334 with 3417 data points) and metabolome data (up to four times; N = 584 with 2330 data points), we explored potential mechanisms underlying the longitudinal metabolic disturbance subtypes. RESULTS: We identified two distinct longitudinal metabolic disturbance subtypes, i.e., metabolically unhealthy aging group (MUAG) (N = 270) and metabolically healthy aging group (MHAG) (N = 1064), characterized by differences in 13 metabolic traits and four major metabolic diseases (type 2 diabetes, hypertension, obesity, and metabolic syndrome). MUAG was associated with cognitive impairment and smaller volumes of brain grey matter, thalamus, caudate, hippocampus, and amygdala. The identified longitudinal metabolic disturbance subtypes may involve biological pathways of immune regulation, key enzyme activity regulation, branched-chain amino acid biosynthesis, and citrate cycle. We identified 11 serum proteins and 31 serum metabolites associated with the MUAG, and revealed a protein-metabolite network involving 26 protein-metabolite associations. CONCLUSIONS: We identified two longitudinal metabolic health-related aging subtypes among middle-aged and elderly adults and uncovered their underlying molecular underpinnings. Our findings may help improve health management of aging populations, offer mechanistic insights, and inform new therapeutic targets for metabolically unhealthy aging.
The hidden hand in retail: a qualitative analysis of how ultra-processed food companies shape consumer purchasing.
Winkler MR, Sundermeir SM, Antonacci CC … +1 more , Laska MN
BMC Med · 2026 Jun · PMID 42304361 · Full text
BACKGROUND: Ultra-processed foods (UPFs) are increasingly recognized for their health harms, yet consumer selection of UPFs is strongly shaped by retail marketing strategies. Despite widespread acknowledgment of these ta...
BACKGROUND: Ultra-processed foods (UPFs) are increasingly recognized for their health harms, yet consumer selection of UPFs is strongly shaped by retail marketing strategies. Despite widespread acknowledgment of these tactics, detailed understanding of their implementation has been limited by restricted access to industry insider information. This study aimed to obtain direct, industry-based insights into the implementation of retail marketing strategies designed to influence consumer purchasing of UPFs. METHODS: We conducted 49 interviews with 27 sales representatives and distributors of major UPF companies and 22 managers of chain and independent stores. Participants provided marketing agreements, planograms, and other business files (n = 46). Using reflexive thematic analysis, we coded and analyzed the 95 documents and identified key themes. RESULTS: Findings reveal UPF manufacturers and retailers deliberately orchestrate the 4Ps-product, placement, price, and promotion-to condition predictable UPF customer selection responses. Strategies included leveraging precise sales data, embedding scripted marketing tactics in contracts, monitoring retailer compliance, refreshing store layouts to create an illusion of choice and innovation, and integrating all 4Ps simultaneously while prioritizing placement. These strategies were organized into six sub-themes across two overarching themes: Guiding Principles of 4Ps Implementation (Simultaneous use of the 4Ps, Placement as a top priority, and Keeping things fresh) and Governance and Surveillance Mechanisms to Best Execute the 4Ps (Monitoring every move, Contracts dictate the 4Ps, and Maintaining store compliance). CONCLUSIONS: Overall, UPF companies exert extensive and deliberate control over retail spaces, challenging the narrative that food and beverage purchases reflect consumer choice. Enhanced regulation of the 4Ps and counter-marketing campaigns that reveal overlooked marketing practices may mitigate UPF companies' influence on customer purchases and thus reduce their related health harms.
Shared genetic architecture between ADHD and intelligence varies across ADHD subtypes.
Zhao Q, Yang K, Liu M … +12 more , Shi Z, Zhao J, Wu Y, Wu Q, Zhai Y, Xu J, Zhang Z, Lei M, Gao Y, Zhang Q, Zheng Y, Liu F
BMC Med · 2026 Jun · PMID 42298576 · Full text
BACKGROUND: Attention-deficit/hyperactivity disorder (ADHD) is a heterogeneous neurodevelopmental condition frequently accompanied by cognitive difficulties. Although previous genetic studies have demonstrated substantia...
BACKGROUND: Attention-deficit/hyperactivity disorder (ADHD) is a heterogeneous neurodevelopmental condition frequently accompanied by cognitive difficulties. Although previous genetic studies have demonstrated substantial overlap between ADHD and intelligence, most have treated ADHD as a single phenotype. However, whether this shared genetic architecture differs across ADHD subtypes remains unclear. METHODS: We conducted a genome-wide cross-trait analysis integrating large-scale genome-wide association study (GWAS) datasets of overall ADHD, its subtypes-childhood ADHD, persistent ADHD, and late-diagnosed ADHD-and intelligence (total N > 300,000). Genome-wide genetic correlations, polygenic overlap, local genetic correlations, and variant-level associations between ADHD phenotypes and intelligence were evaluated to characterize their shared genetic architecture. Shared variants were identified through cross-trait enrichment analyses and subsequently mapped to genes for functional annotation and gene-set enrichment. Bidirectional associations were evaluated using two-sample Mendelian randomization with sensitivity analyses. Additional GWAS datasets were used to validate the robustness of shared loci by assessing the consistency of effect directions. RESULTS: All ADHD phenotypes showed significant negative genetic correlations with intelligence (r ranging from -0.3442 to -0.4205). Despite these modest genome-wide correlations, cross-trait analyses revealed substantial genetic overlap, including polygenic overlap, local genetic correlations, and variant-level associations. We identified 184 loci jointly associated with ADHD traits and intelligence, including 64 novel loci, whereas no shared loci were detected for persistent ADHD under the current analysis. Functional annotation revealed biologically distinct enrichment patterns across subtypes: childhood ADHD loci were linked to early neurodevelopmental processes, while late-diagnosed ADHD loci were enriched in synapse-related and neuronal signaling pathways. Mendelian randomization analyses suggested bidirectional associations, with stronger evidence supporting a directional association from intelligence to ADHD risk. Furthermore, these shared loci showed largely consistent effect directions across additional GWAS datasets, providing support for the robustness of the findings. CONCLUSIONS: The shared genetic architecture between ADHD and intelligence varies across ADHD subtypes, highlighting distinct biological pathways underlying cognitive heterogeneity in ADHD. These findings suggest that the relationship between ADHD liability and general cognitive ability is not uniform across ADHD subtypes and may inform future research on risk stratification and early identification in child and adolescent psychiatry.
Late phase transfusion after CAR T therapy is associated with persistent hematotoxicity and non-relapse mortality in multiple myeloma: a post hoc analysis.
Xia F, Lv B, Li X … +16 more , Tian M, Gu X, Zhou D, Sun Q, Xia J, Qi Y, Zhang H, Qi K, Liu Y, Wang Y, Chen W, Cao J, Yan Z, Shi M, Li D, Zhu F
BMC Med · 2026 Jun · PMID 42286658 · Full text
BACKGROUND: Chimeric antigen receptor T-cell (CAR-T cell) therapy is highly effective for relapsed/refractory multiple myeloma (R/R MM), but hematologic toxicity and the need for blood transfusions remain common. This st...
BACKGROUND: Chimeric antigen receptor T-cell (CAR-T cell) therapy is highly effective for relapsed/refractory multiple myeloma (R/R MM), but hematologic toxicity and the need for blood transfusions remain common. This study examined the patterns of transfusion needs in patients receiving CAR-T cell therapy, analyzed risk factors, and assessed the effects of transfusions on clinical outcomes. METHODS: This retrospective study included 155 R/R MM patients treated with CAR-T cells targeting different antigens. We used multivariate regression and survival analysis to identify risk factors for early (≤ 30 days) and late (> 30 days) transfusion requirements and analyzed their prognostic impact. RESULTS: Of the 155 patients, 38.7% required transfusion in the early phase (≤ 30 days) and 35.5% in the late phase (> 30 days). Early transfusion was associated with acute inflammation and baseline bone marrow reserve but had limited impact on survival. In contrast, late transfusion, particularly red blood cell (RBC) transfusion, was associated with poor outcomes, including significantly reduced overall survival (median OS: 10.87 vs. 37.87 months; P < 0.0001) and progression-free survival (median PFS: 4.93 vs. 17.17 months; P < 0.0001). Late transfusion also correlated with a shallower depth of response (P < 0.001) and higher non-relapse mortality (P = 0.026). CONCLUSIONS: Transfusion requirement after CAR-T cell therapy is a key prognostic factor in MM. The need for early transfusion indicates high inflammation and severe acute toxicity, whereas the need for late transfusion is associated with poor remission, higher non-relapse mortality, and shorter survival. Reducing the need for transfusions could be important for lowering patient burden and improving outcomes.
Utidelone in patients with advanced soft tissue sarcoma refractory to anthracycline and antiangiogenic therapy (UTISARC): a single-arm phase II study.
Liu J, Fu Y, Wang B … +3 more , Tang YF, Deng YT, Jiang Y
BMC Med · 2026 Jun · PMID 42286614 · Full text
BACKGROUND: Treatment options remain limited for patients with advanced or metastatic soft tissue sarcoma after failure of both anthracycline-based chemotherapy and antiangiogenic therapy. Utidelone, an epothilone analog...
BACKGROUND: Treatment options remain limited for patients with advanced or metastatic soft tissue sarcoma after failure of both anthracycline-based chemotherapy and antiangiogenic therapy. Utidelone, an epothilone analog, has demonstrated antitumor activity across a broad spectrum of preclinical models and clinical trials. This single-arm, phase II trial was designed to assess the efficacy and safety of utidelone in a heavily pretreated population. METHODS: This study enrolled patients aged 18 years or older with locally advanced or metastatic soft tissue sarcoma who had previously been treated with anthracycline-based chemotherapy and antiangiogenic tyrosine kinase inhibitors. Participants received utidelone via a 90-minute intravenous infusion at a dose of 30 mg/m² on days 1-5 of each 21-day treatment cycle, continuing until disease progression or the occurrence of unacceptable toxicity. The primary endpoint was median progression-free survival. The secondary endpoints included the objective response rate, overall survival and safety. RESULTS: Between August 2022 and March 2025, a total of 27 patients were included in the study. The median age was 55 years (range, 30-68). There were 15 patients with leiomyosarcoma, 3 with dedifferentiated liposarcoma, 3 with epithelioid sarcoma, 2 with angiosarcoma, and 4 with other types of sarcoma. The median number of prior systemic therapy regimens was 2 (range, 1-4). The median treatment exposure was 5 cycles (range, 1-10). Two patients achieved a partial response, resulting in an objective response rate of 7%. The median progression-free survival was 4.6 months (95% confidence interval, 3.6-5.6). Overall survival data were immature, with only 9 death events (33%) observed. The estimated 12-month overall survival rate was 80%. Most adverse events were grade 1 or 2 in severity. The most frequently observed grade ≥ 3 adverse event was peripheral neuropathy (11%). CONCLUSIONS: In this exploratory trial, utidelone demonstrated preliminary antitumor activity and a manageable safety profile in patients with refractory soft tissue sarcoma. Further exploration of novel combination therapies involving utidelone is warranted to enhance its clinical utility. TRIAL REGISTRATION: ChiCTR2200062161, registered on July 26, 2022.
NNMT and the methylation sink: integrating metabolism, epigenetics and immunity in cancer.
Li L, Ma Y, Pan Y … +7 more , Li B, Chen C, Wang Q, Fu Y, Fan X, Wang S, Wang Z
BMC Med · 2026 Jun · PMID 42286598 · Full text
Nicotinamide N-methyltransferase (NNMT) is a methyltransferase that uses S-adenosyl-L-methionine (SAM, cofactor) to catalyze the N-methylation of nicotinamide (NAM, substrate), yielding 1-methylnicotinamide (MNAM) and S-...
Nicotinamide N-methyltransferase (NNMT) is a methyltransferase that uses S-adenosyl-L-methionine (SAM, cofactor) to catalyze the N-methylation of nicotinamide (NAM, substrate), yielding 1-methylnicotinamide (MNAM) and S-adenosyl-homocysteine (SAH). By consuming SAM and generating SAH, NNMT establishes a cellular "methylation sink" that couples metabolic reprogramming to epigenetic remodeling across DNA, RNA and proteins. Accumulating evidence shows that NNMT is upregulated in multiple malignancies, across both cancer cells and stromal lineages such as cancer-associated fibroblasts and pericytes. Its activity correlates with key hallmarks of cancer progression, including tumor growth, metastasis potential, metabolic rewiring, immune evasion, angiogenesis, maintenance of stem-like states, and resistance to therapy (including chemotherapy, targeted agents, and radiotherapy). These properties nominate NNMT as a candidate biomarker for diagnosis and stratification and as a tractable therapeutic node. We synthesize current knowledge of NNMT-driven cellular and microenvironmental mechanisms in tumorigenesis and progression, and summarize emerging therapeutic strategies, which include competitive inhibitors targeting the substrate or cofactor binding sites, microenvironment-activated prodrugs, and rational combinations with immune checkpoint blockade and targeted therapy to provide a conceptual and translational framework for developing NNMT-directed interventions.
Palliative care for the people without medical insurance in Germany: an empirical ethical approach.
Zimmer M, Sahm A
BMC Med · 2026 Jun · PMID 42277859 · Full text
BACKGROUND: People without medical insurance often lack access to medical care, increasing their risk of chronic diseases and reducing life expectancy. This disparity likely extends to end-of-life care, when patients are...
BACKGROUND: People without medical insurance often lack access to medical care, increasing their risk of chronic diseases and reducing life expectancy. This disparity likely extends to end-of-life care, when patients are especially vulnerable. The main research question was whether outpatient and inpatient palliative care facilities regularly treat uninsured patients. Based on the results, the study initiated an ethical reflection on the circumstances of uninsured palliative patients in Germany. METHODS: The study ran for 15 months from 2024 to 2025 1494 inpatient hospices, outpatient hospice services and specialized outpatient palliative care (SOPC) in Germany were invited to participate in an online questionnaire. The questionnaire contained questions about the care of uninsured patients with palliative care needs. A univariate descriptive analysis was used. Based on the results, ethical reflections on overlapping vulnerability were conducted, focusing especially on how living without medical insurance and its related circumstances interact from an intersectional perspective. RESULTS: People without medical insurance, usually aged 40-65 years, received care at 41 (45.6%) inpatient hospices, 63 (29.3%) outpatient hospice services, and 29 (48.3%) SOPCs. Social workers usually made the requests. Funding gaps were reported by 10 (24.3%) inpatient hospices, 18 (8.4%) outpatient hospice services, and 55 (60.3%) SOPCs. 49 (54.4%) of inpatient hospices, 133 (61.9%) of outpatient hospice services, and 37 (61.7%) of SOPCs lacked knowledge about care options for uninsured patients ,. Fewer uninsured patients were cared for than had requested care, although there was a high level of willingness to provide palliative care to people without medical insurance. CONCLUSIONS: The findings suggest that palliative care facilities do not regularly treat uninsured patients in Germany. Access to established palliative care institutions seems more difficult for the uninsured. These results indicate major inequalities in the provision of health care in Germany, especially in phases when patients are highly dependent on caregivers and therefore in need of protection. To address these issues, networking between medical services for the uninsured and palliative care services should be further strengthened. Precise legal regulations are ethically necessary alongside measures to ensure low-threshold access to palliative care and targeted training for medical professionals.
Extracellular matrix biomarkers of T-cell infiltration and tumor fibrosis predict response to nivolumab ± ipilimumab with SBRT in biliary tract cancer: insights from the CheckPAC trial.
Rasmussen MB, Chen IM, Johansen JS … +5 more , Theile S, Markussen A, Christensen TD, Karsdal MA, Willumsen N
BMC Med · 2026 Jun · PMID 42277831 · Full text
BACKGROUND: Biliary tract cancer (BTC) is an uncommon malignancy with limited treatment options and poor prognosis. BTC is typically characterized by a desmoplastic, collagen-rich extracellular matrix (ECM), which has be...
BACKGROUND: Biliary tract cancer (BTC) is an uncommon malignancy with limited treatment options and poor prognosis. BTC is typically characterized by a desmoplastic, collagen-rich extracellular matrix (ECM), which has been linked to immune exclusion and therapy resistance. Although immune checkpoint inhibitors (ICI) combined with gemcitabine/cisplatin have become first-line treatment for advanced BTC, durable responses are rare, and predictive biomarkers for immunotherapy are lacking. We investigated the pharmacodynamic and predictive potential of liquid, ECM-derived biomarkers reflecting cytotoxic T-cell activity (granzyme B-degraded type IV collagen [C4G]) and fibrotic activity (pro-peptides of type III [PRO-C3] and VI [PRO-C6] collagens, matrix metalloprotease-degraded type I [reC1M], III [C3M], and IV collagens [C4M]) in patients with metastatic BTC receiving combined immunotherapy and radiotherapy. METHODS: Biomarkers (C4G, PRO-C3, PRO-C6, reC1M, C3M, and C4M) were measured in serum from 61 patients with metastatic BTC enrolled in CheckPAC (NCT02866383), treated with stereotactic body radiotherapy (SBRT) combined with nivolumab (n = 19) or nivolumab/ipilimumab (n = 42). Biomarkers were assessed at baseline and day 60. Associations of baseline levels and on-treatment changes with overall survival (OS) and clinical benefit rate were evaluated; longitudinal analyses used a landmark approach. RESULTS: Higher baseline PRO-C3 and reC1M were associated with lack of clinical benefit (p < 0.05) and shorter OS (p < 0.05). In multivariable Cox regression adjusting for CA 19 - 9, ECOG performance status, and modified Glasgow Prognostic Score, PRO-C3 remained independently associated with OS. Longitudinally, C4G increased from baseline to day 60 in all patients with clinical benefit (p < 0.001), whereas no consistent changes were observed among patients without clinical benefit. For the landmark analyses, C4G increase was associated with clinical benefit (p = 0.007) and longer OS (p = 0.0045). Patients with low PRO-C3 and increased C4G at day 60 showed the most favorable survival, including a subgroup without RECIST-defined clinical benefit (p < 0.001). CONCLUSIONS: Serological biomarkers reflecting tumor fibrosis (PRO-C3) and cytotoxic T-cell infiltration (C4G) were associated with clinical benefit and OS and showed pharmacodynamic changes during therapy in patients with metastatic BTC treated with SBRT plus ICI. These biomarkers enable tracking of pharmacodynamic response to ICI, while independent validation is necessary to ensure their predictive utility in immunotherapy.
AI-assisted diagnosis of cardiac amyloidosis using electrocardiograms and echocardiography: a multicenter retrospective study in China.
Zhang S, Wan Z, Hu Y … +4 more , Wu M, Zhang X, Tian Z, Zhang S
BMC Med · 2026 Jun · PMID 42277821 · Full text
BACKGROUND: Cardiac amyloidosis (CA) is an under-recognized cause of left-ventricular hypertrophy (LVH) that is often misclassified as hypertrophic cardiomyopathy (HCM) or hypertensive heart disease (HHD). We aimed to de...
BACKGROUND: Cardiac amyloidosis (CA) is an under-recognized cause of left-ventricular hypertrophy (LVH) that is often misclassified as hypertrophic cardiomyopathy (HCM) or hypertensive heart disease (HHD). We aimed to develop and externally validate an AI model using electrocardiograms (ECG) and echocardiography to distinguish CA from other LVH aetiologies. METHODS: A retrospective, multicenter study was conducted, with a derivation cohort collected from PUMCH (290 CA patients, 215 HCM patients, and 160 HHD patients) and an external validation cohort recruited from 10 other hospitals across China (126 CA patients, 240 HCM patients, and 190 HHD patients). Twenty-eight clinical, ECG, and echocardiographic predictors were included, and we selected the top 7 important features by recursive feature elimination strategy. The Super Learner model combines predictions from 11 machine learning models, and model performance was evaluated via macro-AUC, accuracy, precision, F1 score, and etc. We developed a simplified scoring system to diagnose CA, and classifying patients into three groups based on CA probability to minimize misdiagnosis risk. RESULTS: Ranking by feature importance, the top seven features were included and used for model construction, including Sokolow-Lyon index, interventricular septal thickness, systolic blood pressure, left-ventricular posterior wall thickness, tricuspid annular plane systolic excursion, average E/e', and left-ventricular ejection fraction. The Super Learner model, combining Extra Trees, Histogram-based Gradient Boosting, LightGBM, and Multi-Layer Perceptron, achieved the highest AUC of 0.97 (95% confidence interval [CI]: 0.95-0.98). In external validation, the super learner model achieved AUCs of 0.96 (95% CI: 0.95-0.98) for CA, 0.93 (0.91-0.95) for HCM, and 0.91 (0.89-0.94) for HHD. And the simplified scoring system also showed robust diagnostic performance (AUC 0.90, 95% CI 0.86-0.93). CONCLUSIONS: We developed an AI model integrating ECG and echocardiography that provides a clinically applicable and noninvasive framework for CA screening and diagnosis, and implementation through a WeChat-based screening program. However, its performance and generalizability should be further validated in larger prospective multicenter studies.
Exercise reduces hepatic pre-metastatic niche formation via TREM-1 signaling in kupffer cells.
Yang R, Haykal T, Tohme C … +8 more , He Z, Zhang H, Gebran A, Liu S, Simmons RL, Geller DA, Yazdani HO, Tohme S
BMC Med · 2026 Jun · PMID 42277794 · Full text
BACKGROUND: Tumor-derived exosomes contribute to the formation of a hepatic pre-metastatic niche (PMN) by activating Kupffer cells (KCs) and hepatic stellate cells (HSCs), thereby promoting metastatic seeding. Whether ex...
BACKGROUND: Tumor-derived exosomes contribute to the formation of a hepatic pre-metastatic niche (PMN) by activating Kupffer cells (KCs) and hepatic stellate cells (HSCs), thereby promoting metastatic seeding. Whether exercise modulates exosome-driven PMN formation and subsequent liver metastasis remains unclear. METHODS: Eight-week-old male mice were randomized to sedentary (SED) and exercise training (ExT) groups. Mice were pre-educated with cancer-derived exosomes to induce a hepatic PMN and subsequently subjected to experimental liver metastasis model. Kupffer cells were isolated for transcriptomic and mechanistic analyses. Pharmacologic inhibition of TREM-1 signaling was performed to assess pathway-specific effects. RESULTS: Exercise training significantly attenuated hepatic PMN formation and reduced metastatic burden in exosome-educated mice. Exosome uptake by KCs was comparable between SED and ExT groups; however, ExT reduced KC inflammatory activation. Transcriptomic analysis identified downregulation of the TREM-1 signaling pathway in ExT KCs. Reduced TREM-1 activity was associated with diminished NF-κB activation in HSCs, decreased fibronectin deposition, and increased HSC apoptosis. Pharmacologic TREM-1 inhibition recapitulated key anti-metastatic effects observed with exercise. CONCLUSIONS: Exercise training attenuates tumor exosome-induced hepatic pre-metastatic niche formation through modulation of Kupffer cell inflammatory signaling, in part via suppression of TREM-1. Targeting TREM-1 signaling significantly reduces experimental liver metastasis and may represent a therapeutic approach that partially recapitulates the anti-metastatic effects of exercise. These findings support further investigation into exercise and innate immune modulation as strategies to influence early metastatic niche biology.
Excess cardiovascular risk associated with community-acquired lower respiratory tract infections: a population-based nested self-controlled case-series.
Rijk MH, van Vught LA, Platteel TN … +6 more , van Royen FS, Little P, Geersing GJ, Rutten FH, Bruijning-Verhagen PCJL, Venekamp RP
BMC Med · 2026 Jun · PMID 42271461 · Full text
BACKGROUND: Lower respiratory tract infections (LRTI) are common and can trigger acute cardiovascular events. Previous studies focussing on this association only reported relative effect measures, leaving the population...
BACKGROUND: Lower respiratory tract infections (LRTI) are common and can trigger acute cardiovascular events. Previous studies focussing on this association only reported relative effect measures, leaving the population impact largely unknown. METHODS: This population-based study was based on routine health care data of the Julius General Practitioners' Network in the Netherlands and included patients aged ≥40 years presenting with an LRTI to general practice between 2016-2019. The burden of acute cardiovascular events following LRTI was assessed in three consecutive steps. First, 90-day incidence rates of acute cardiovascular events following LRTI were mapped for major adverse cardiac and cerebrovascular events (MACCE), venous thromboembolism (VTE), and new-onset atrial fibrillation (nAF). Second, incidence rate ratios (IRR) within 90 days following LRTI were estimated per cardiovascular event type, using a self-controlled case-series analysis. Third, excess cardiovascular risk associated with LRTI was calculated. RESULTS: In total, 11,065 patients contributed 16,497 LRTI episodes. The 90-day incidence rate per 1000 LRTI patients was 4.2 (3.3 to 5.3, n = 69) for MACCE, 2.7 (1.9 to 3.6, n = 44) for VTE, and 6.6 (5.4 to 8.1, n = 96) for nAF. Incidence rate ratios (IRR) of cardiovascular events within 90 days following LRTI were 1.3 (1.0 to 1.8) for MACCE, 6.8 (4.4 to 10.4) for VTE, and 2.9 (2.3 to 3.7) for nAF. For all cardiovascular event types, IRRs were highest in the first week following LRTI. Per 1000 LRTI patients, 0.5 (-0.5 to 1.6) to 1.1 (0.1 to 2.4) excess MACCE, 2.1 (1.1 to 3.6) to 3.0 (1.8 to 4.9) excess VTE, and 2.3 (1.1 to 3.7) to 4.4 (2.9 to 6.2) excess nAF diagnoses were associated with LRTI. CONCLUSIONS: The temporal increase in cardiovascular risk following LRTI culminates in approximately five to nine excess acute cardiovascular events per 1000 LRTI patients aged ≥40 years. Given the large number of LRTI patients during seasonal outbreaks, this implies a need for targeted preventative interventions and patient-focussed campaigns to increase seasonal vaccine uptake.
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