Category: Statistics

Int J Legal Med. 2026 Aug 1. doi: 10.1007/s00414-026-03935-6. Online ahead of print.

ABSTRACT

BACKGROUND: Molecular autopsy is increasingly used in unexplained sudden death, but reported diagnostic yield varies across sequencing eras, cohort types, and variant-classification frameworks. This review evaluated ACMG-corrected diagnostic yield, genomic architecture, VUS burden, and downstream family translation.

METHODS: This PRISMA-based systematic review and meta-analysis was registered in PROSPERO (CRD420251082728). Studies reporting postmortem genetic testing in sudden unexplained death were included. Quantitative diagnostic-yield synthesis included 44 core molecular autopsy studies comprising 4,041 index cases; 35 studies contributed family-translation data. Random-effects meta-analysis was performed, and subgroup analyses were conducted by sequencing strategy and age group.

RESULTS: The pooled ACMG-corrected diagnostic yield was approximately 13%, with substantial heterogeneity. Broader sequencing approaches showed modestly higher yield than candidate/restricted panels (OR 1.36, 95% CI 1.09-1.70; p = 0.006), but with greater VUS burden. Young adult/adult cohorts showed the highest pooled yield, while infant/pediatric cohorts demonstrated broader multisystem genomic architecture and higher VUS burden. Recurrent substrates included RYR2, SCN5A, KCNQ1, KCNH2, TTN, and MYBPC3. Family-translation data were available from 35 studies, including 25 overlapping index-case cohorts; genotype-positive relatives, phenotype-positive relatives, segregation analysis, and clinically actionable interventions were frequently reported.

CONCLUSIONS: Contemporary ACMG-compatible molecular autopsy provides modest but clinically meaningful diagnostic yield. Its major value extends beyond postmortem diagnosis, supporting family-based preventive genomic medicine through cascade screening, phenotype correlation, and targeted risk stratification.

PMID:42538417 | DOI:10.1007/s00414-026-03935-6

Eur J Clin Nutr. 2026 Jul 31. doi: 10.1038/s41430-026-01796-1. Online ahead of print.

ABSTRACT

BACKGROUND: The impact of meal timing and eating window on mortality and life expectancy remains unclear.

METHODS: This cohort study included 31,044 adults aged 40 years and older from the National Health and Nutrition Examination Survey 1999-2018. The meal timing and the eating window were estimated from a 24-h dietary recall.

RESULTS: During a median (IQR) follow-up of 8.6 (4.5-13.0) years, 7129 deaths were documented. Compared with a first meal within 7:00-8:00, the hazard ratios (HRs) and 95% CIs of all-cause mortality were 1.10 (1.02-1.18), 1.19 (1.05-1.34), and 1.29 (1.10-1.51) for a first meal within 8:00-10:00, 10:00-12:00, and after 12:00, respectively. Compared with a last meal within 19:00-20:00, the HR of all-cause mortality was 1.13 (1.03-1.25) for a last meal before 19:00, and 1.27 (1.06-1.54) for eating after midnight. The associations were also observed for cardiovascular mortality. The association between eating window and cardiovascular mortality risk varied by first meal timing. At the age of 50 years, the estimated life expectancy was on average 2.46 (0.61-4.28) years shorter among participants having a first meal after 12:00 and 2.35 (0.82-5.14) years shorter among those having a last meal after midnight compared with reference groups.

CONCLUSIONS: Later first meals and earlier or later last meals were associated with higher mortality risks and shorter life expectancy. These findings suggest that meal timing may be a modifiable behavioral factor associated with mortality risk and life expectancy.

PMID:42538400 | DOI:10.1038/s41430-026-01796-1

Mol Psychiatry. 2026 Jul 31. doi: 10.1038/s41380-026-03771-5. Online ahead of print.

ABSTRACT

Objective neural markers that reflect the underlying pathophysiological mechanisms of affective disorders are needed to facilitate early identification of individuals most at risk of future affective disorders and ultimately provide neural targets to guide therapeutic interventions. Using an emotional n-back paradigm designed to examine working memory (WM) and emotional regulation (ER) capacity, we previously showed that WM-related elevated left dlPFC activity (a key node of the central executive network (CEN)) and elevated right precuneus activity (a key node of the default mode network (DMN)), as well as ER-related elevated left dlPFC activity were positively associated with future depression severity in young adults at risk for affective disorders. We now aimed to replicate and extend these previous longitudinal findings by examining relationships among right precuneus activity and left dlPFC activity during WM and ER tasks and future depression severity in a new independent young adult sample (n = 77: 50 female, age = 24.68), and a larger combined sample (n = 121: 83 female, age = 23.81) comprising the original and new samples. The Hamilton Rating Scale for Depression (HAM-D) and Young Mania Rating Scale (YMRS) were measured at 12 months post scan to assess future depression and mania/hypomania severity respectively. In the new sample, we showed patterns of left dlPFC activity and right precuneus activity during WM, and left dlPFC activity during ER that were consistent with the original sample. In both the new and combined samples, future depression severity was robustly predicted by WM-related left dlPFC activity and right precuneus activity, and ER-related left dlPFC activity (all ps < 0.05 qFDR). These findings were specific to future depression severity. The effect sizes (pseudo R-squared values) for the full models including all IVs in the new and combined samples ranged from approximately 25-43%, with left dlPFC and right precuneus activity during WM explaining 15.59% of variance in future depression severity in the new sample; and left dlPFC activity during ER explaining 14.63% of variance in future depression severity in the combined sample. These replicated, longitudinal findings provide candidate neural markers to guide risk identification and targeting of new interventions for individuals with and those at risk for future affective disorders.

PMID:42538394 | DOI:10.1038/s41380-026-03771-5

Cancer Epidemiol. 2026 Jul 31;104:103166. doi: 10.1016/j.canep.2026.103166. Online ahead of print.

ABSTRACT

BACKGROUND: Alcohol and tobacco are among the leading preventable causes of cancer worldwide and frequently co-occur. While both are well-established independent carcinogens, their combined effects remain insufficiently characterized and inconsistently interpreted across cancer types.

OBJECTIVE: This review synthesizes epidemiological and mechanistic evidence on alcohol-tobacco interaction in carcinogenesis, distinguishing statistical interaction from evidence of biological mechanism.

METHODS: We examined interaction patterns across major cancer sites and assess the extent to which combined effects exceed individual risks. Particular attention is given to methodological approaches used to quantify interaction, including additive and multiplicative models and their implications for causal interpretation.

RESULTS: Current evidence supports a heterogeneous landscape of interaction. Strong and consistent synergistic effects are observed for upper aerodigestive tract cancers, whereas evidence is heterogeneous for hepatocellular carcinoma and context-dependent for breast cancer. By contrast, lung, pancreatic, and early-onset colorectal cancers show predominantly independent effects, with tobacco remaining the principal driver of lung cancer. Mendelian randomization studies support independent causal effects of smoking and, for some cancers, alcohol, but have not assessed their joint interaction.

CONCLUSION: To reconcile these findings, we propose a unified conceptual framework in which alcohol-tobacco interaction is viewed as a continuum ranging from strong biological synergy to functional independence, depending on tissue-specific vulnerability and exposure context. Finally, we identify key gaps in the field, including the need for standardized interaction metrics, prospective cohorts capturing joint exposure trajectories, integrative multi-omics approaches, and combined Mendelian randomization studies. Addressing these challenges will be essential to improve risk stratification and inform both precision oncology strategies and targeted, combined prevention efforts.

PMID:42537280 | DOI:10.1016/j.canep.2026.103166

J Psychosom Res. 2026 Jul 17;211:112931. doi: 10.1016/j.jpsychores.2026.112931. Online ahead of print.

ABSTRACT

BACKGROUND: Fatigue is a debilitating symptom in autoimmune liver disease, but prospective research on fatigue in Primary Sclerosing Cholangitis (PSC) remains limited. This study aimed to estimate fatigue frequency in patients with PSC and explore cross-sectional and prospective biopsychosocial associations with fatigue severity.

METHODS: This prospective study included 226 patients with PSC. Fatigue severity was assessed using the PBC-40 fatigue domain at baseline and six-month follow-up. Biomedical, psychological and social variables were assessed using clinical records, blood biomarkers and self-report measures. Descriptive statistics and multivariable linear regression models were used to examine cross-sectional and prospective associations with fatigue severity.

RESULTS: At baseline, 19% of patients reported clinically significant fatigue. Patients with fatigue reported greater psychobehavioral burden and impairment across several domains. Cross-sectionally, greater fatigue severity was significantly associated with higher depressive symptom severity (p < 0.001) and greater fear-avoidance behavior (p < 0.001), whereas biomedical disease severity markers were not independently associated with fatigue severity. At six months, most patients without baseline fatigue remained below the clinical threshold (92%), while fatigue persisted in 79% of patients with baseline fatigue. Prospectively, greater fear-avoidance behavior (p < 0.001) and detectable IL-6 serum level (p = 0.02) were associated with greater fatigue persistence over time.

DISCUSSION: Fatigue represents a clinically relevant and persistent symptom burden in PSC. Findings support a multidimensional biopsychosocial conceptualization of fatigue involving psychobehavioral and inflammatory processes and may provide useful directions for future mechanistic and interventional research.

PMID:42537269 | DOI:10.1016/j.jpsychores.2026.112931

J Neurosurg Pediatr. 2026 Jul 31:1-6. doi: 10.3171/2026.3.PEDS25681. Online ahead of print.

ABSTRACT

OBJECTIVE: It is unclear whether shunt survival differs for infants in whom prior endoscopic third ventriculostomy with choroid plexus cauterization (ETV/CPC) failed compared with those treated initially by shunt placement. Results among four previous studies spanning a range of age groups have suggested either no effect or a protective effect of prior endoscopic treatment on shunt survival. The aim of this study was to determine whether prior ETV/CPC positively impacts shunt survival among infants with hydrocephalus regardless of etiology.

METHODS: The authors conducted a historical cohort review of all patients under 12 months corrected age who underwent ventriculoperitoneal shunt (VPS) placement either with or without prior ETV/CPC at their institution between December 2008 and December 2023. Statistical analyses included Cox regression modeling, Kaplan-Meier survival curves, and log-rank testing to evaluate the time to shunt failure.

RESULTS: The study included 122 infants with and 46 infants without prior ETV/CPC who underwent VPS placement. There were no statistically significant differences between groups regarding sex, race, gestational age at birth, or corrected age at initial treatment for hydrocephalus. The distribution of etiologies and initial frontal-occipital horn ratios (FOHRs) were similar. The median pre-shunt FOHR was greater in the ETV/CPC group. The patients in the primary shunt placement group were all candidates for ETV/CPC based on retrospective review. Seventy-one infants (58%) with prior ETV/CPC remained free of shunt revision compared with 17 infants (37%) with primary shunt placement (OR 2.4, 95% CI 1.1-5.1; p = 0.01). The estimated 2-year shunt survival probability was 75% with and 50% without prior ETV/CPC (log-rank p = 0.001). The estimated 5-year survival was 60% with and 45% without prior ETV/CPC (p = 0.045).

CONCLUSIONS: Infants who underwent ETV/CPC prior to VPS placement had better shunt survival than those who did not. ETV/CPC might reduce the risk of subsequent shunt failure, indicating the potential benefit of the procedure even when it fails.

PMID:42537233 | DOI:10.3171/2026.3.PEDS25681

JMIR Med Inform. 2026 Jul 31;14:e88854. doi: 10.2196/88854.

ABSTRACT

BACKGROUND: Online health care consultation provides patients with broad access to physicians, but also presents the challenge of selecting a suitable doctor in the absence of triage guidance. Patients have multifaceted needs, prioritizing not only recommendation accuracy but also physician service quality, and diversity of physician expertise. Furthermore, the sparsity of patient interaction data intensifies the difficulty of providing balanced and effective recommendations.

OBJECTIVE: This study aims to develop a multiobjective physician recommendation method that simultaneously optimizes recommendation accuracy, service quality, and diversity of physician expertise while addressing the data sparsity challenge inherent in online health care platforms.

METHODS: We propose dynamic graph-based bacteria colony optimization for multiobjective physician recommendation (DyGMO-PR), a dynamic graph-based multiobjective optimization method. It integrates bacterial colony optimization with an evolving physician relationship graph. Our approach features a novel graph-based encoding scheme, a chemotaxis-inspired graph-walking strategy for stable search, and a dynamic graph evolution mechanism that learns implicit physician relationships to enhance recommendation quality under sparse data conditions.

RESULTS: Evaluation on a real-world dataset comprising 10,493 consultation records from 1256 patients and 1377 physicians demonstrates the effectiveness of DyGMO-PR. Our method consistently outperforms 6 state-of-the-art multiobjective recommendation algorithms. Using a recommendation list length of 6 as an example, DyGMO-PR achieves an accuracy of 0.876, a service quality of 0.873, and a diversity of 0.720, surpassing the best-performing baseline by 7.4%, 3.1%, and 8.1%, respectively. DyGMO-PR also attains the highest hypervolume value (0.696 at K=6) and the highest recall (0.380 at K=6). Case studies and graph analysis further demonstrate the method’s effectiveness in generating interpretable and balanced recommendation lists.

CONCLUSIONS: DyGMO-PR offers an effective solution for multiobjective physician recommendation. It provides a flexible and practical foundation for building more responsive and reliable recommender systems in online health care.

PMID:42537221 | DOI:10.2196/88854

JMIR Mhealth Uhealth. 2026 Jul 31;14:e48828. doi: 10.2196/48828.

ABSTRACT

BACKGROUND: Many frameworks and tools are available to evaluate the quality of mobile health apps (MHAs), which are increasingly used by health care professionals (HCPs) for accessing medical information, clinical decision support, and communication. However, existing tools are not well equipped to assess the quality of apps designed for HCPs from their perspectives.

OBJECTIVE: We aimed to develop a new tool based on the Mobile App Rating Scale (MARS) to capture the unique perspectives of HCPs on MHAs. We then conducted a psychometric analysis of this new questionnaire to determine its effectiveness in assessing the quality of MHAs designed specifically for HCPs from their perspectives.

METHODS: This study was conducted in 2 phases. In phase 1, the original MARS tool was adapted for HCPs through expert panel review and subsequent qualitative interviews, resulting in the development of the pMARS (MARS for health care professionals) tool. This phase focused on establishing face and content validity. Qualitative interviews were conducted with HCPs from a tertiary hospital in Singapore to gather their perspectives on the tool’s structure, clarity, applicability, and usability. In phase 2, we invited HCP participants to complete pMARS based on their experience with the LabMed app, an mHealth tool designed to provide medical laboratory-related information to HCPs. We established the construct validity of pMARS through multiple psychometric techniques. Internal consistency reliability was measured using the Cronbach α, while structural equation modeling was used to examine the interrelationships among latent constructs. Additionally, we used item response theory (IRT) to evaluate each item’s impact on latent constructs of interest, that is, discriminative performance of individual items within each domain.

RESULTS: Based on the results from phase 1, the pMARS comprised 26 items across 5 domains: engagement, functionality, aesthetics, information, and subjective quality, refined through interviews with 10 HCPs. In phase 2 (n=218), pMARS demonstrated good internal consistency reliability across all domains (Cronbach α=0.855-0.931). Structural equation modeling demonstrated that functionality had the strongest influence on end-user willingness to use, recommend, and purchase the MHA (P<.001). IRT identified that customization and interactivity of the engagement domain had a weak impact on latent constructs, whereas entertainment had a higher impact. Ease of use and gestural design had a weak impact on the functionality domain, whereas arrangement and size of content and quantity and quality had a strong impact on the aesthetics and information domains, respectively.

CONCLUSIONS: This study reports the development and psychometric analysis of pMARS. Our findings demonstrate strong internal consistency reliability and construct validity, supporting its potential use in health care. Further research should validate pMARS across diverse MHAs and contexts and apply IRT to further refine its precision and efficiency.

PMID:42537209 | DOI:10.2196/48828

Phys Rev Lett. 2026 Jul 17;137(3):031501. doi: 10.1103/q81l-xfkx.

ABSTRACT

We show that the canonical formulation of the semiclassical Einstein equation, where the matter terms in the constraints are replaced by expectation values of the corresponding operators in quantum states, is inconsistent due to the nonclosure of the resulting constraint algebra.

PMID:42537109 | DOI:10.1103/q81l-xfkx

Phys Rev Lett. 2026 Jul 17;137(3):030802. doi: 10.1103/m1tx-9mx1.

ABSTRACT

Device-independent (DI) certification allows the verification of quantum systems based solely on observed statistics, without assumptions about their internal structure. While self-testing, the strongest DI certification, of a wide range of quantum states and measurements is done, the self-testing of quantum operations remains underdeveloped. Here, we show in a proof-of-principle way that any quantum unitary can be self-tested within the DI paradigm. For our purpose, we utilize the framework of quantum networks with multiple independent sources. Our Letter provides a fundamental step toward certifying quantum interactions directly from data, without detailed modelling assumptions. Moreover, the result also serves as a crucial ingredient for quantum computation, where verifying that quantum gates perform as intended is essential for building secure and reliable quantum processors.

PMID:42537105 | DOI:10.1103/m1tx-9mx1