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Nevin Manimala Statistics

Digital twins and virtual cohorts: How is synthetic data used for real-world evidence?

Epidemiol Prev. 2026 Jan-Feb;50(1):94-99. doi: 10.19191/EP26.1.A902.022.

ABSTRACT

Synthetic data are artificially generated information with the aim of imitating real data. They are designed to preserve the statistical characteristics of the original population while ensuring high levels of privacy, which makes them particularly useful in contexts where confidentiality is crucial. Measuring the value of synthetic data means assessing the similarity with the original data, the ability to produce results comparable to those obtained with real data, and the potential risks of privacy breaches. However, some risks remain, including the possible re-identification of individuals, the danger of amplification of biases already present in the original data, and the difficulty in validating the quality of synthetically generated data. At present, synthetic data represent an emerging and promising technology in various fields, however their use in epidemiology, particularly in observational settings, is still debated and requires further investigation and evaluation.

PMID:41854006 | DOI:10.19191/EP26.1.A902.022

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Nevin Manimala Statistics

Activity-Informed Network Analysis Reveals Keystone Microbes Shaping Freshwater Ecosystem Function

Environ Microbiol Rep. 2026 Apr;18(2):e70245. doi: 10.1111/1758-2229.70245.

ABSTRACT

Freshwater lakes are dynamic ecosystems, with varying oxygen dynamics that influence microbiome structure, composition, and transcriptomic activity. In many freshwater studies, ecological function and abundance metrics are used to discover keystone species; however, it is well established that abundance does not equal activity. Despite the existence of long-term time series spanning multiple years, no previous study has looked at how microbial community and activity (metatranscriptomics) are influenced by shifting oxygen conditions across depths at the microbial network level. In this study, we leverage metagenome-assembled genomes and transcriptomic activity to identify keystone taxa in the ecosystem. Using the SPIEC-EASI and CARlasso methods, we mapped key microbial associations and used permutation-based analyses to assess the robustness of keystone identification. Our results reveal that a taxon’s ecological centrality is context-dependent and that many species identified as keystone by abundance alone do not exhibit corresponding transcriptional activity. Notably, members of Bacteroidota and other lineages emerged as keystone taxa only when both abundance and activity were considered. Our study underscores the importance of combining metagenomic and metatranscriptomic approaches for accurate identification of functionally relevant keystone species in freshwater ecosystems, providing a framework for future microbial ecology studies.

PMID:41853994 | DOI:10.1111/1758-2229.70245

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Nevin Manimala Statistics

A preliminary validation of the traumatic grief inventory-kids-caregiver-report (TGI-K-CR)

Eur J Psychotraumatol. 2026 Dec;17(1):2638015. doi: 10.1080/20008066.2026.2638015. Epub 2026 Mar 19.

ABSTRACT

BACKGROUND: Prolonged grief disorder (PGD) is included in the Diagnostic and Statistical Manual of Mental Disorders text-revised fifth edition (DSM-5-TR) and in the International Classification of Diseases Eleventh Edition (ICD-11). While PGD screening instruments exist for adults, these instruments are not applicable to children. Caretakers play a crucial role in screening for PGD in children.

OBJECTIVE: We evaluated the psychometric properties of the Traumatic Grief Inventory-Kids-Caregiver-Report (TGI-K-CR) to screen for DSM-5-TR and ICD-11 PGD in children.

METHOD: On a website with information about grief, 196 Dutch caregivers (82% woman; Mage = 44) completed questions about their own and their child’s (47% girls; Mage = 11; 44% lost a parent) background and loss-related characteristics (77% of deaths resulted from illness). Caregivers completed the TGI-K-CR and a self-report measure about their own PGD intensity. Factor structure and internal consistency of DSM-5-TR and ICD-11 PGD items were examined separately. T-tests and correlation analyses examined whether caregiver-ratings of PGD intensity in children differed as a function of background- and loss-related characteristics. Provisional cut-offs for both criteria sets were determined.

RESULTS: Confirmatory factor analyses showed support for two distinct, but related, factors for DSM-5-TR and ICD-11 PGD items. We found strong internal consistency (ω = .85 for DSM-5-TR; ω = .87 for ICD-11), while some factor loadings were poor. In support of known-groups validity, DSM-5-TR and ICD-11 PGD intensity were higher in children when caregivers reported higher PGD intensity for themselves and when deaths occurred more recently. ROC analyses showed optimal cut-off scores of ≥46 and ≥52 to determine probable caseness for DSM-5-TR and ICD-11 PGD, respectively, when summing all 16 items.

CONCLUSIONS: The psychometric properties of the TGI-K-CR seem promising, but more research among larger samples is needed. This caregiver screening tool for PGD in children (aged 8-18) may advance child bereavement research and care.

PMID:41853993 | DOI:10.1080/20008066.2026.2638015

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Nevin Manimala Statistics

Self-reported versus clinician-evaluated symptom assessment and diagnosis of ICD-11 PTSD and CPTSD: a comparison between the International Trauma Interview and the International Trauma Questionnaire

Eur J Psychotraumatol. 2026 Dec;17(1):2635917. doi: 10.1080/20008066.2026.2635917. Epub 2026 Mar 19.

ABSTRACT

Background: The ICD-11 introduced distinct criteria for Posttraumatic Stress Disorder (PTSD) and Complex PTSD (CPTSD), necessitating validated assessment tools. While the International Trauma Questionnaire (ITQ) is a widely used self-report measure, the International Trauma Interview (ITI) is a structured clinician-administered interview considered a gold standard. This study investigated the correspondence between ITQ and ITI symptom and diagnostic classifications in a treatment-seeking veteran population.Methods: A sample of 108 Danish veterans completed both the ITQ and ITI. We calculated descriptive statistics, bivariate correlations, and Cohen’s κ values to assess agreement for individual symptom items and diagnostic categories (ICD-11 PTSD, CPTSD, and PTSD or CPTSD combined), using the ITI as the reference standard. Sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) were also determined.Results: ITQ scores were consistently higher than ITI scores across all symptom domains. Total symptom scores for PTSD, DSO, and CPTSD showed strong associations between instruments (r = .74 to .82, all p < .001). Agreement for individual symptom items varied from fair to substantial (κ = .33 to .70). The combined diagnosis of PTSD or CPTSD showed moderate agreement (κ = .60) with high sensitivity (0.94) and PPV (0.90). However, agreement for ICD-11 PTSD alone was fair (κ = .38), with low PPV (0.39) despite good sensitivity (0.65).Conclusion: The ITQ consistently reported higher symptom endorsement than the ITI. While the ITQ shows strong convergent validity for overall symptom burden and high sensitivity for screening trauma-related psychopathology (PTSD or CPTSD combined), its limited agreement for standalone ICD-11 PTSD diagnosis suggests it should not be used as a sole diagnostic tool. Comprehensive clinical interviews remain crucial for definitive diagnosis, while the ITQ can serve as an effective screening instrument.

PMID:41853968 | DOI:10.1080/20008066.2026.2635917

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Nevin Manimala Statistics

Genomic insights into the tmexCD-toprJ: plasmid-mediated evolution, dissemination and diversity in bacterial populations

J Antimicrob Chemother. 2026 Mar 4;81(4):dkag107. doi: 10.1093/jac/dkag107.

ABSTRACT

BACKGROUND: The plasmid-mediated tigecycline resistance gene tmexCD-toprJ has emerged in clinical and animal isolates, but its epidemiological spread and plasmid adaptation mechanisms remain unclear.

METHODS: We characterized tmexCD-toprJ-carrying plasmids from the PLSDB database through comprehensive bioinformatic analyses, revealing their genetic features and potential inter-species transmission routes.

RESULTS: Genomic analysis of 197 tmexCD-toprJ-carrying plasmids revealed significant backbone diversity, clustering into 18 groups and 12 singletons. The 30 identified host species were predominantly Klebsiella pneumoniae (K. pneumoniae) (53.3%), followed by Pseudomonas aeruginosa (P. aeruginosa) (16.8%) and Klebsiella quasipneumoniae (K. quasipneumoniae) (4.1%). MOB-suite typing classified 53.8% as conjugative, 5.6% mobilizable and 40.61% non-mobilizable. Over half of the tmexCD-toprJ-carrying plasmids were predicted to contain the MOBH family. Among the identified variants, tmexCD1-toprJ1, tmexCD2-toprJ2 and tmexCD3-toprJ1 representing the predominant forms. TmexCD1-toprJ1 was linked to IncFIB/IncHI1B/rep_cluster_1254 plasmids, while tmexCD2-toprJ2 associated with diverse replicons, enabling cross-species spread. A total of 14 plasmids co-localized tmexCD-toprJ with carbapenemase (blaNDM/KPC) and mcr genes, forming high-risk resistance platforms. Notably, a 36 483 bp insertion in IncP/rep_cluster_1115 plasmids disrupted tmexC6D6-toprJ1b and carried heavy metal resistance genes.

CONCLUSIONS: These findings enhance our understanding of the diversity of tmexCD-toprJ-carrying plasmids. The convergence of tmexCD-toprJ with carbapenemase and polymyxin resistance genes in clinically prevalent plasmids underscores an urgent need for enhanced surveillance targeting complete genetic environments.

PMID:41853961 | DOI:10.1093/jac/dkag107

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Nevin Manimala Statistics

Diagnostic Delay in Desquamative Gingivitis: An Observational Cohort Study

Oral Dis. 2026 Mar 19. doi: 10.1111/odi.70276. Online ahead of print.

ABSTRACT

OBJECTIVES: Non-plaque-induced gingivitis encompasses a heterogeneous group of conditions as defined in the 2017 Classification of Periodontal and Peri-Implant Diseases and Conditions. Recognition is challenging and often leads to diagnostic delay. This study aimed to evaluate diagnostic delay in a cohort of patients with non-plaque-induced gingivitis presenting as desquamative gingivitis, and to identify associated factors.

MATERIALS AND METHODS: In this observational study, patients were recruited from public and private oral medicine centres. Participants completed a questionnaire collecting demographic, social, and clinical information related to their condition. Association between variables and diagnostic delay were analyzed using the Student’s t-test (significance p < 0.05).

RESULTS: Eighty-six patients (43 from private and 43 from public centres) were enrolled. The mean diagnostic delay was 10 months. No statistically significant associations were observed between diagnostic delay and age, gender, symptom presence, smoking habits, or definitive diagnosis. In contrast, diagnostic delay was significantly higher in private oral health centre patients (11.19 months vs. 8.75 months p < 0.05) and in patients living more than 34 km from the diagnostic centre (p < 0.05).

CONCLUSIONS: Proximity to specialized diagnostic centres and the type of centre (public vs. private) were identified as determinants to reduce diagnostic delay in patients with desquamative gingivitis.

PMID:41853924 | DOI:10.1111/odi.70276

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Nevin Manimala Statistics

Joint Modeling of Quality of Life and Survival Using a Bayesian Approach in a Retrospective Time Scale

Stat Med. 2026 Mar;45(6-7):e70505. doi: 10.1002/sim.70505.

ABSTRACT

Improving patients’ quality of life (QoL) is one of the primary goals of palliative care clinical trials. However, a significant challenge in this area is the “truncation by death problem,” where QoL data cannot be observed after a patient dies, potentially introducing bias into statistical analyses. Understanding the impact of truncation by death when estimating the association between QoL and exposure or treatment is essential, especially when a relatively large proportion of subjects die during a study. To address this issue, we propose a Bayesian joint modeling framework that considers dependencies at both the individual and cluster levels while examining longitudinal QoL trajectories and survival outcomes simultaneously. This approach builds on existing joint modeling methods by incorporating cluster-level random effects. We model QoL on a retrospective scale relative to the time of death, while linking survival via both the subject and cluster-level random effects. The longitudinal sub-model also allows for flexible, non-linear QoL trajectories, which are modeled using penalized regression splines. For the survival sub-model, we use a proportional hazards frailty model with a Weibull baseline hazard. The model is estimated using a Bayesian framework, implemented via Markov Chain Monte Carlo (MCMC) sampling. To evaluate the performance of our method, we conducted a comprehensive simulation study including scenarios with different numbers of clusters. We also show results from applying this novel methodology to data from the Reducing End of Life Symptoms with Touch (REST) study.

PMID:41853920 | DOI:10.1002/sim.70505

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Nevin Manimala Statistics

Covariate Adjustment in Basket Trials Borrowing Information Across Subgroups

Stat Med. 2026 Mar;45(6-7):e70492. doi: 10.1002/sim.70492.

ABSTRACT

Basket trials are an efficient approach to simultaneously evaluate a single therapy across multiple diseases where patients share a common molecular target. Bayesian hierarchical models (BHMs) are widely used to estimate the treatment effects while accounting for heterogeneity between patient subgroups within a basket trial. However, the use of analysis of covariance (ANCOVA) with treatment-by-covariate interaction terms, in this context of patient heterogeneity and small samples, has been largely unexplored, despite the widespread use of ANCOVA for improving estimation precision in traditional settings from a frequentist perspective. In this paper, we propose two covariate-adjusted BHMs that incorporate ANCOVA into the data model to enhance the estimation precision in basket trials, wherein borrowing of information is permitted across subgroups to a certain extent. Specifically, both ANCOVA without treatment-by-covariate interaction terms and ANCOVA with interaction terms are explored in the analysis of basket trials. We perform a simulation study to demonstrate the advantages of covariate-adjusted BHMs compared to unadjusted BHMs, as well as frequentist ANCOVA models. The BHMs are then retrospectively applied to the analysis of the MAJIC study, a randomized controlled basket trial involving two subtypes of blood cancer.

PMID:41853914 | DOI:10.1002/sim.70492

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Nevin Manimala Statistics

Characterization of CD123 expression by mast cells in systemic mastocytosis with multicolor flow cytometry

Cytometry B Clin Cytom. 2026 Mar 19. doi: 10.1002/cyto.b.70023. Online ahead of print.

ABSTRACT

Systemic mastocytosis (SM) is a clonal mast cell (MC) disorder characterized by aberrant immunophenotypes, including expression of CD25, CD2, and occasionally CD30. CD123, the α-subunit of the interleukin-3 receptor, is a therapeutic target in hematologic malignancies and has been reported to be expressed on neoplastic MCs by immunohistochemistry (IHC) with prognostic implications. This study aims to characterize CD123 expression in SM by flow cytometry. We retrospectively analyzed 142 bone marrow samples from 79 SM patients (81 diagnostic samples) and 25 controls with normal MC immunophenotype. Flow cytometry was performed using a clinically validated 9-color mast cell tube which included CD123. Data collected included SM subtype, clinical and laboratory features, MC burden, and marker expression. Statistical analyses were performed in R. CD123 was expressed on MCs in 91% of SM cases (ISM 92%, SM-AHN 94%, SSM 100%, ASM 100%, MCL 50%). Median percentage of MCs positive for CD123 was 53.9% (IQR 8.1-83.4). Compared to prior IHC data (overall 64% positivity), flow cytometry demonstrated more cases with CD123 expression by MCs. No significant correlations were observed between CD123 expression and serum tryptase, KIT D816V allele burden, or MC burden. CD123 is frequently expressed on neoplastic MCs in SM by flow cytometry, across all subtypes. These findings support further investigation of CD123 as a therapeutic target and warrant correlation with IHC and clinical outcomes in larger cohorts.

PMID:41853900 | DOI:10.1002/cyto.b.70023

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Nevin Manimala Statistics

Enhanced recovery after surgery in diverticular disease: A multicenter comparison with colorectal cancer

Scand J Surg. 2026 Mar 19:14574969261431953. doi: 10.1177/14574969261431953. Online ahead of print.

ABSTRACT

BACKGROUND AND AIMS: ERAS protocols are widely used in colorectal surgery, yet their impact on outcomes in diverticular disease (DD) is unclear. The primary aim of this study was to compare postoperative complication rates after left-sided colon resections for either DD or left-sided colonic cancer within an ERAS pathway, the secondary aim was to assess ERAS protocol compliance.

METHODS: This retrospective multicenter cohort study used data from the Swedish ERAS® Interactive Audit System (EIAS) from 2010 to 2020. All participating centers consecutively register elective colorectal procedures in patients aged ⩾ 18 years. We included all adult patients undergoing elective left-sided colonic or sigmoid resection at participating centers, where all procedures are mandatorily registered within a standardized ERAS pathway, with no additional exclusions. ERAS protocol compliance (pre- and intraoperative items), postoperative symptoms, and postoperative complications were assessed according to ERAS® guidelines and compared between diagnostic groups. Associations between variables and outcomes were evaluated using logistic regression.

RESULTS: A total of 3774 patients were included (879 with DD and 2895 with cancer). Patients in the DD group were younger and had fewer comorbidities. ERAS compliance was similar between groups (86.3% for DD vs 86.7% for cancer). In multivariable analysis, there was no statistically significant difference in severe complications (Clavien-Dindo grade III-IV) between the DD and cancer groups (11.8% vs 13.1%; OR = 0.97, 95% CI = 0.87-1.09). However, DD was associated with a higher rate of overall complications (39.2% vs 36.5%; OR = 1.27, 95% CI = 1.07-1.52), particularly infectious complications (17.0% vs 12.1%; OR = 1.55, 95% CI = 1.23-1.97), including intra-abdominal abscesses (3.5% vs 2.3%; OR = 1.62, 95% CI = 1.01-2.60). In addition, DD patients were more likely to experience postoperative pain that delayed hospital discharge (5.2% vs 2.4%, OR = 1.78, 95% CI = 1.17-2.70).

CONCLUSIONS: Despite similar adherence to the ERAS protocol, surgery for DD was associated with a higher overall rate of postoperative complications and similar rates of severe complications as surgery for colonic cancer. The considerable risk of complications should be carefully considered when counseling patients with DD for elective surgery.

PMID:41853898 | DOI:10.1177/14574969261431953