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PubMed1975

A double logistic comparison of growth patterns of normal children and children with Down's syndrome.

A double logistic model was used to compare six parameters of growth in standing height of 31 children with Down's syndrome with 136 children from the California Guidance Study. Multivariate analysis of variance of the growth data showed that while there were significant differences in all six parameters favouring the normal over the Down's children, there were no significant differences with respect to error of fit. Multivariate analysis with final height as a covariate revealed that differences between the normal and the Down's children in the prepubertal and adolescent components were explainable by differences in final height. In summary, the double logistic model, when applied to this sample of Down's children, identified those well defined logistic components which are characteristic of the growth of normal children, the differences being those of degree, not of form.

Analysis of Variance↗

PubMed1978

[Determining the average posteruptive age of teeth from the results of cross-sectional studies (author's transl)].

If results of cross-sectional studies must be used as a basis for setting up models of development of caries in permanent teeth, then the average rather than individual posteruptive age of teeth has to be resorted to. Data available for this purpose had been obtained from a total of 54,000 children living in two G.D.R. cities, namely, Plauen and Karl-Marx-Stadt, as well as from two surveys made in 1959 and 1971, respectively. Calculation of the average posteruptive age of teeth assumes good knowledge of the distribution of dates of eruption in a population. Of the three types of distribution considered, namely, normal, lognormal, and log-logistic distribution, the log-logistic model proved to be superior to others because of better adaptation to the data available. The method of calculating the posteruptive age of teeth is described and illustrated by use of a number of examples. Since one of the two surveys (namely that which was made in Karl-Marx-Stadt in 1971) was made after twelve years' drinking water fluoridation, it was possible to study the effect of fluoridation upon the eruptive behavior of permanent teeth. The results of this study confirmed those obtained during previous investigations.

Adolescent↗

PubMed2025

Disparities in Outcomes for Patients With Inflammatory Bowel Disease at a Private vs Public Hospital in New York City.

BACKGROUND: In patients with inflammatory bowel disease (IBD), social determinants of health contribute to health inequalities. We aimed to compare patients with IBD treated at a private nonprofit vs public hospital in New York City. METHODS: We performed a retrospective study of adult patients with Crohn's disease or ulcerative colitis with established IBD care. Patient demographics, disease characteristics, healthcare utilization, treatment modalities, and clinical outcomes were collected. Using a series of linear mixed and logistic models, the differences between care at a private nonprofit vs public hospital were assessed while controlling for factors that differed between them. RESULTS: Our study included 418 patients with IBD, 209 from each hospital. Compared with public hospital patients, private hospital patients were more likely to be White, be non-Hispanic, and have private insurance (all P = .0005) and less likely to face housing instability (P < .0001), face unemployment (P = .0004), be current smokers (P = .03), or be foreign born (P < .0001). Patients at the private hospital were more likely to have multiple anti-tumor necrosis factor (P = .0001) and biologic use (P < .0001). Public hospital patients were less likely to be considered endoscopically adherent (odds ratio [OR], 0.377; P = .001) and more likely to visit the emergency department (OR, 5.01; P < .0001) and be hospitalized (OR, 1.92; P = .05). CONCLUSIONS: Our study is the first to identify significant differences in patient demographics, disease phenotype, treatments and clinical outcomes between patients treated for IBD at a private nonprofit vs public hospital. Our data suggest that social determinants of health drive disparities in the utilization of healthcare facilities.

Humans↗

PubMed2026

Tertiary lymphoid structure transcriptomic signatures show limited and cohort-dependent value for predicting axillary nodal involvement in oestrogen receptor-positive luminal breast cancer.

Tertiary lymphoid structures (TLS) are associated with prognosis in solid tumours. Their value for predicting axillary nodal involvement in oestrogen receptor-positive luminal breast cancer remains uncertain. Three published TLS signatures were scored by single-sample gene set enrichment analysis in oestrogen receptor-positive luminal tumours. The Cancer Genome Atlas Breast Invasive Carcinoma cohort (TCGA-BRCA) included 632 cases, of which 379 met strict consensus. METABRIC included 1086 cases, of which 663 met strict consensus. Logistic models adjusted for age and pathological tumour stage. Strict consensus, majority vote, and continuous scores were compared. Performance assessment included bootstrapped changes in area under the receiver-operating-characteristic curve, Brier scores, calibration, and decision-curve analysis. Survival was evaluated in METABRIC and explored in TCGA-BRCA. Strict-consensus TLS status was not associated with nodal positivity in TCGA-BRCA (adjusted odds ratio: 0.95, 95% confidence interval: 0.62-1.45, P = 0.822). METABRIC was similar (odds ratio: 0.76, 95% confidence interval: 0.55-1.06, P = 0.105). Full-cohort METABRIC analyses detected small majority-vote and continuous-score associations, absent in TCGA-BRCA. Across specifications, bootstrapped changes in area under the receiver-operating-characteristic curve ranged from 0.0002 to 0.0089, with minimal Brier-score improvement and no stable decision-curve benefit. In METABRIC, the univariable overall survival association attenuated after age adjustment (hazard ratio: 1.33-1.10). TCGA-BRCA survival analyses were nonsignificant. TLS transcriptomic signals showed small, cohort-dependent associations with nodal status but no reproducible or clinically meaningful incremental predictive value. These data do not support replacing sentinel lymph node biopsy with a TLS signature in oestrogen receptor-positive luminal breast cancer.

breast cancer↗

PubMed2025

Genome-wide association study of angiotensinogen levels and key single nucleotide polymorphism associations with blood pressure.

OBJECTIVE: The renin angiotensin aldosterone system plays a key role in circulatory homeostasis. We sought to identify genetic determinants of measured plasma angiotensinogen levels and subsequently evaluate the association of these single nucleotide polymorphisms (SNPs) with blood pressure (BP) and hypertension in a multiethnic population. METHODS: Genome-wide association study (GWAS) of plasma angiotensinogen levels, measured using an enzyme-linked immunoassay, was conducted in 4899 Multi-Ethnic Study of Atherosclerosis (MESA) participants (self-identified as White, n = 1865; Hispanic, n  = 1113; Black, n  = 1224; and Chinese, n  = 629). Linear and logistic models examined the association between SNPs with angiotensinogen and hypertension, respectively. Mediation analysis evaluated the effect of angiotensinogen on BP/hypertension through the top SNPs identified by GWAS. RESULTS: In the analysis utilizing all participants, 115 SNPs were associated with angiotensinogen ( P  < 5 × 10 -8 ), including lead SNP rs4762(G>A) in exon 2 ( P  = 1.51E -100 ) and rs5050(T>G) in the promoter region ( P  = 2.26E -69 ) of the AGT gene. Race/ethnic-specific analyses identified rs4762(G>A) as the lead SNP for White and Hispanic participants, whereas Black and Chinese participants had rs5050(T>G) and rs16852311(G>C), respectively. Both rs4762(G>A) and rs5050(T>G) indirectly increased systolic BP, diastolic BP, and the odds of hypertension through its effect of increasing angiotensinogen. CONCLUSIONS: Our findings demonstrate racial/ethnic differences in genetic effects on angiotensinogen levels across multiple SNPs. AGT rs4762(G>A) and rs5050(T>G) impact BP and hypertension through a mediated effect via angiotensinogen, though opposing direct effects may mask the overall association.

Humans↗

PubMed2026

Artificial Intelligence for Diagnosing Meibomian Gland Dysfunction: A Systematic Review and Meta-Analysis of Diagnostic Test Accuracy Studies.

PURPOSE: To identify, appraise, and synthesize the performance of artificial intelligence-based meibography reading as compared with human graders in diagnosing meibomian gland dysfunction. METHODS: We followed Cochrane methodology and reporting guidelines for diagnostic test accuracy reviews. To assess potential risk of bias and applicability, we used a modified Quality Assessment of Diagnostic Accuracy Studies-2 checklist. We applied bivariate logistic models to estimate summary sensitivity and specificity when appropriate and used the GRADE framework to rate the certainty of the evidence. RESULTS: We identified 14 eligible studies involving 5511 predominantly middle-aged participants (average age: 27-55 years) who were primarily female (≥54.5%). A total of 18,926 meibography images were obtained through noncontact infrared (11 studies) or in vivo confocal microscopy (three studies). Two studies reported external validation of deep learning models, 12 reported internally validated models, and one reported both. All but one study had high risk of bias in at least one domain; 12 studies raised high or intermediate concern about applicability. Based on three external evaluations, the summary sensitivity and specificity for diagnosing meibomian gland dysfunction from normal glands were 97.5% (95% confidence interval: 77.5%-99.8%) and 85.5% (95% confidence interval: 47.3%-97.5%). Sources of heterogeneity in internally validated models included study population, case mix, and others. The overall evidence was very low to low certainty because of imprecision, high risk of bias, and concerns about applicability. CONCLUSIONS: Artificial intelligence-based meibography grading appears less accurate than human graders. Future studies should adopt rigorous designs, including a more diverse participant pool (or image set), and external validation.

Humans↗

PubMed2025

Associations of Genetic Liability to Six Psychiatric Disorders With Cardiometabolic Diseases.

IMPORTANCE: Individuals with psychiatric disorders have increased risk of cardiometabolic diseases (CMDs). Evaluating how psychiatric genetic liability relates to CMD may clarify mechanisms. OBJECTIVE: Identify genetic overlap between psychiatric disorders and CMDs independent of cross-disorder pleiotropy, BMI, and smoking. DESIGN SETTING AND PARTICIPANTS: Three Northern European cohorts (the Swedish Twin Registry, the Estonian Biobank, and the Norwegian Mother, Father and Child Cohort Study [MoBa]) totaling 355,159 individuals. Associations with CMDs were estimated as adjusted odds ratios (AORs) from logistic models mutually adjusted for all psychiatric PRSs and in models additionally adjusting for body mass index (BMI) and smoking. Cohort-specific AORs were pooled by inverse-variance weighting. MAIN OUTCOMES AND MEASURES: Exposures were PRSs for attention-deficit/hyperactivity disorder (ADHD), major depressive disorder (MDD), anxiety disorder, posttraumatic stress disorder (PTSD), bipolar disorder, and schizophrenia. Outcomes were diagnoses of CMDs (hyperlipidemia, obesity, type 2 diabetes, hypertensive diseases, arteriosclerosis, ischemic heart disease, heart failure, thromboembolic disease, cerebrovascular disease, and arrhythmias), ascertained from electronic health records. RESULTS: The MDD PRS was associated with increased risk of all CMDs across analyses (AORs ranged from 1.13 [95% CI, 1.10-1.15] for heart failure to 1.02 [95% CI, 1.00-1.05] for arrhythmias). The ADHD PRS was associated with increased risk of all CMDs (AOR ranged from 1.11 [95% CI, 1.09-1.12] for obesity to 1.02 [95% CI, 1.01-1.03] for hyperlipidemia), however associations where attenuated when adjusting for BMI and smoking (lifestyle adjusted AOR for obesity: 1.03 [95% CI, 1.02-1.05]). When not mutually adjusting for all psychiatric PRSs, anxiety disorder and PTSD PRSs were associated with all CMDs; these associations diminished after adjustment. The bipolar and schizophrenia PRSs were inversely associated with most CMDs (AOR for schizophrenia PRS and obesity, 0.93 [95% CI, 0.92-0.94]). CONCLUSIONS AND RELEVANCE: Associations between psychiatric PRSs and CMDs diverged: ADHD, MDD, anxiety disorder, and PTSD PRSs were positively associated with CMDs, whereas bipolar and schizophrenia PRSs were inversely associated. Genetic liability to MDD showed robust associations with CMDs independent of cross-disorder pleiotropy, BMI, and smoking status, whereas associations between the ADHD PRS and CMDs were largely attenuated after adjustment for BMI and smoking.

Journal Article↗

PubMed2024

Molecular genomic and epigenomic characteristics related to aspirin and clopidogrel resistance.

BACKGROUND: Mediators, genomic and epigenomic characteristics involving in metabolism of arachidonic acid by cyclooxygenase (COX) and lipoxygenase (ALOX) and hepatic activation of clopidogrel have been individually suggested as factors associated with resistance against aspirin and clopidogrel. The present multi-center prospective cohort study evaluated whether the mediators, genomic and epigenomic characteristics participating in arachidonic acid metabolism and clopidogrel activation could be factors that improve the prediction of the aspirin and clopidogrel resistance in addition to cardiovascular risks. METHODS: We enrolled 988 patients with transient ischemic attack and ischemic stroke who were evaluated for a recurrence of ischemic stroke to confirm clinical resistance, and measured aspirin (ARU) and P2Y12 reaction units (PRU) using VerifyNow to assess laboratory resistance 12 weeks after aspirin and clopidogrel administration. We investigated whether mediators, genotypes, and promoter methylation of genes involved in COX and ALOX metabolisms and clopidogrel activation could synergistically improve the prediction of ischemic stroke recurrence and the ARU and PRU levels by integrating to the established cardiovascular risk factors. RESULTS: The logistic model to predict the recurrence used thromboxane A synthase 1 (TXAS1, rs41708) A/A genotype and ALOX12 promoter methylation as independent variables, and, improved sensitivity of recurrence prediction from 3.4% before to 13.8% after adding the mediators, genomic and epigenomic variables to the cardiovascular risks. The linear model we used to predict the ARU level included leukotriene B4, COX2 (rs20417) C/G and thromboxane A2 receptor (rs1131882) A/A genotypes with the addition of COX1 and ALOX15 promoter methylations as variables. The linear PRU prediction model included G/A and prostaglandin I receptor (rs4987262) G/A genotypes, COX2 and TXAS1 promoter methylation, as well as cytochrome P450 2C19*2 (rs4244285) A/A, G/A, and *3 (rs4986893) A/A genotypes as variables. The linear models for predicting ARU (r = 0.291, R2 = 0.033, p < 0.01) and PRU (r = 0.503, R2 = 0.210, p < 0.001) levels had improved prediction performance after adding the genomic and epigenomic variables to the cardiovascular risks. CONCLUSIONS: This study demonstrates that different mediators, genomic and epigenomic characteristics of arachidonic acid metabolism and clopidogrel activation synergistically improved the prediction of the aspirin and clopidogrel resistance together with the cardiovascular risk factors. TRIAL REGISTRATION: URL: https://www. CLINICALTRIALS: gov ; Unique identifier: NCT03823274.

Humans↗

PubMed2026

Epigenetic Clocks of Biological Aging and Cognitively Healthy Longevity: The Women's Health Initiative Memory Study.

BACKGROUND: Little is known about whether epigenetic age acceleration (EAA) clocks are capable of predicting exceptional longevity with or without preserved cognitive function. METHODS: We examined 5844 women from the Women's Health Initiative Memory Study. Fifteen epigenetic clocks were measured at baseline (1996-1999). Longevity outcomes were defined as: 1) survival to age 90 with preserved cognition (n = 1726, 29.5%); or 2) survival to age 90 with cognitive impairment (n = 956, 16.4%); vs. 3) death before age 90 (n = 2611, 44.7%). Logistic regression models examined associations between the 15 clocks and survival to age 90 (vs. death before age 90), adjusting for covariates. Multinomial logistic regression models examined associations with survival to age 90 without cognitive impairment and survival to age 90 with cognitive impairment (each vs. death before age 90), also adjusting for covariates. RESULTS: Each standard deviation increase in EAA for the first-generation clocks was associated with 7%-18% reduced odds of survival to age 90 vs. earlier death. Stronger associations were observed for second- and third-generation clocks, including AgeAccelGrim2 (OR = 0.66; 95% CI 0.61-0.71), PCGrimAge (OR = 0.64; 95% CI 0.59-0.69), PCPhenoAge (OR = 0.73; 95% CI 0.68-0.78) and DunedinPACE (OR = 0.77; 95% CI 0.72-0.82). None of the clocks was more strongly associated with survival to age 90 with preserved cognition than with survival to age 90 with cognitive impairment, relative to death before age 90. CONCLUSION: All epigenetic clocks were associated with exceptional longevity, but none were associated with cognitive healthspan. Developing clocks that can differentiate long survival with and without preserved cognitive function is critical.

Healthspan↗

PubMed2025

Real-world clinical impact of plasma cell-free DNA metagenomic next-generation sequencing assay.

OBJECTIVE: To describe the real-world clinical impact of a commercially available plasma cell-free DNA metagenomic next-generation sequencing assay, the Karius test (KT). METHODS: We retrospectively evaluated the clinical impact of KT by clinical panel adjudication. Descriptive statistics were used to study associations of diagnostic indications, host characteristics, and KT-generated microbiologic patterns with the clinical impact of KT. Multivariable logistic regression modeling was used to further characterize predictors of higher positive clinical impact. RESULTS: We evaluated 1000 unique clinical cases of KT from 941 patients between January 1, 2017-August 31, 2023. The cohort included adult (70%) and pediatric (30%) patients. The overall clinical impact of KT was positive in 16%, negative in 2%, and no clinical impact in 82% of the cases. Among adult patients, multivariable logistic regression modeling showed that culture-negative endocarditis (OR 2.3; 95% CI, 1.11-4.53; P .022) and concern for fastidious/zoonotic/vector-borne pathogens (OR 2.1; 95% CI, 1.11-3.76; P .019) were associated with positive clinical impact of KT. Host immunocompromised status was not reliably associated with a positive clinical impact of KT (OR 1.03; 95% CI, 0.83-1.29; P .7806). No significant predictors of KT clinical impact were found in pediatric patients. Microbiologic result pattern was also a significant predictor of impact. CONCLUSIONS: Our study highlights that despite the positive clinical impact of KT in select situations, most testing results had no clinical impact. We also confirm diagnostic indications where KT may have the highest yield, thereby generating tools for diagnostic stewardship.

Humans↗

PubMed2026

Protein Profiling Identifies Biomarkers for Predicting Disease Severity in Anti-NMDAR Encephalitis.

Anti-N-methyl-D-aspartate receptor (NMDAR) encephalitis is a severe autoimmune neurological disorder characterized by pathogenic antibodies against the NMDAR. A systematic protein profiling approach is warranted to identify biomarkers capable of predicting disease status. An Olink proximity extension assay (PEA) profiled 91 inflammation-related proteins from anti-NMDAR encephalitis patients. Disease severity or prognosis were assessed by CASE score or mRS score at 6-month follow-up. Patients were stratified into distinct molecular clusters using unsupervised clustering. Logistic regression models incorporating selected biomarkers were developed to predict disease severity and prognosis, followed by absolute quantification using ELISA. Patients were classified into four consensus clusters. Clusters 1 and 2 corresponded to the mild group, while Cluster 3 represented the severe group, consistent with CASE score above 6. Cluster 4 showed heterogeneous clinical features. Elevated serum levels of IL-10, IL-6, and SIRT2, as well as increased CSF levels of CXCL10, CXCL11, and MMP10, were positively associated with severe disease. Conversely, several proteins including LTA and CCL11, CCL8, TGFB1, CXCL6 were associated with severe disease or unfavorable 6-month outcomes. A logistic regression model combining serum CXCL6 and CCL11 with CSF MMP10 achieved an area under the curve (AUC) of 0.95 for predicting disease severity. Serum CCL11 alone showed predictive value for 6-month prognosis, with an AUC of 0.79. These findings delineate distinct protein signatures associated with clinical heterogeneity of anti-NMDAR encephalitis. Prediction models incorporating multiple biomarkers may provide an approach for disease severity stratification and prognosis forecast.

Humans↗

PubMed2026

Sex-specific biomarkers predict bone mineral density loss at the contralateral hip after hip fracture.

OBJECTIVE: To identify inflammatory and hormonal biomarkers that predict bone loss at the contralateral (non-fractured) hip following hip fracture in males and females. METHODS: White participants who were not receiving pre-fracture glucocorticoids, sex-hormone therapy, or bone-active medications (100 males, 76 females) with hip fractures. Data were collected within 22 days of hip fracture and at 2, 6, and 12 months follow-up. Biomarkers were categorized into tertiles: estradiol, 25-hydroxyvitamin D3/D2, intact parathyroid hormone (iPTH), interleukin-1 receptor antagonist (IL-1RA), interleukin-6 (IL-6), insulin-like growth factor-1 (IGF-1), soluble tumor necrosis factor-α receptor 1, sex hormone-binding globulin, and testosterone. Femoral neck bone mineral density (BMD) at the contralateral hip was assessed, and losses exceeding the mean decline were classified as greater than average. Logistic regression models, stratified by sex, were adjusted for confounders and evaluated selected biomarker associations. RESULTS: Among males, the 2nd (OR = 4.79, P = 0.012) and 3rd (OR = 6.36, P = 0.005) IGF-1 tertiles were associated with greater odds of BMD loss than the 1st tertile. The 3rd iPTH tertile (OR = 3.79, P = 0.037) was similarly associated with increased odds. Among females, the 3rd (OR = 0.20, P = 0.031) IL-1RA tertile was associated with lower odds of BMD loss compared to the 1st tertile, while the 2nd IL-6 tertile (OR = 5.99, P = 0.036) was associated with higher odds. CONCLUSION: These findings suggest that inflammatory and hormonal biomarkers may be sex-specific predictors of accelerated BMD loss following hip fracture.

Biomarkers↗

PubMed2026

No association between alcohol consumption and hip osteoarthritis: a diverse national analysis of 87,585 adults from the "All of Us" research program.

INTRODUCTION: Hip osteoarthritis (OA) is estimated to affect 62.6 million individuals by 2050. A probable link exists between alcohol use and hip OA. However, the results are inconsistent, and the relationship between alcohol and hip OA remains speculative. To address these gaps, this study aimed to utilize the diverse, nationally representative All of Us Research Program dataset to explore the association between alcohol consumption and hip OA. METHODS: This retrospective case-control study utilized data from the All of Us Research Program Controlled Tier Dataset v8. 17,517 hip OA cases and 70,068 controls were identified. A 1:4 case-to-control matching ratio was applied based on age and sex. Alcohol use frequency was categorized into five levels: Never, Monthly or Less, Two to Four Times per Month, Two to Three Times per Week, and Four or More Times per Week. Multivariable logistic regression models evaluated the association between alcohol use frequency and hip OA after adjusting for demographic and clinical variables. RESULTS: Multivariable analysis found that alcohol use frequency was not significantly associated with hip OA. Compared to never users, participants with low (OR 0.98, 95% CI 0.93-1.04, P = 0.583), moderate (OR 0.99-1.01, all P > 0.05), and high (OR 1.02, 95% CI 0.95-1.09, P = 0.599) levels of alcohol consumption had no statistically significant differences in odds of hip OA. Female sex, Asian race, diabetes, hypertension, hyperlipidemia, and nicotine dependence increased the odds of hip OA. CONCLUSION: Any level of alcohol consumption was not significantly associated with the odds of hip OA. This study adds valuable insight to the current body of conflicting evidence. Further prospective studies appear warranted to shed light on the long-term effects of different alcoholic beverages on different joints. Key Points • This study found no significant association between any degree of alcohol consumption and the odds of developing hip osteoarthritis. • Utilizing data from 87,585 adults in the NIH "All of Us" Research Program, this is the first study to analyze this relationship in a large, nationally representative population. • The research provides clarity to previously conflicting literature by demonstrating that alcohol lacks a clear harmful or protective effect on the clinical course of the disease. • The analysis highlights that independent risk factors such as Asian race, nicotine dependence, and components of metabolic syndrome increase the odds of hip osteoarthritis.

Humans↗

PubMed2026

Genetic Ancestry and Colorectal Cancer in the All of Us Dataset.

IMPORTANCE: Genetic ancestry may complement biological, behavioral, and clinical factors in understanding colorectal cancer (CRC) disparities; yet, ancestry-informed analyses in CRC remain limited. OBJECTIVE: To characterize associations of genetic ancestry with CRC burden, age at diagnosis, and age-specific risk, and to develop a multiethnic CRC risk-prediction model. DESIGN, SETTING, AND PARTICIPANTS: This retrospective cohort study used All of Us data from July 1986 to October 2023, with follow-up through last visit or death (median [IQR], 133.1 [57.1-186.5] months); analyses were conducted from February to June 2026. All of Us is a US research cohort with linked electronic health record (EHR) and short-read whole-genome sequencing (srWGS) data. All of Us Research Program participants with srWGS and linked EHR data were included, except those with hereditary polyposis or Lynch syndrome. EXPOSURES: Genetically inferred ancestry categories and principal components. MAIN OUTCOMES AND MEASURES: Any CRC was the primary outcome. Associations were evaluated using Fisher exact tests, cumulative incidence functions with Gray tests, cause-specific and Fine-Gray subdistribution hazard models, and pooled multivariable logistic regression. Prediction models used penalized least absolute shrinkage and selection operator and extreme gradient boosting (XGBoost). RESULTS: Among 316 624 participants (median [IQR] age, 56.3 [40.2-68.2] years; 172 327 [54.4%] of European ancestry; 191 705 female [61.2%]; 121 585 male [38.8%]), 2914 (0.9%) developed CRC. European ancestry was associated with higher odds of CRC vs all other ancestries combined (odds ratio, 1.50; 95% CI, 1.39-1.62). The median age at CRC diagnosis was older in European (63.4 [53.9-71.2] years) than in American admixed-Latino, African, East Asian, and Other ancestry groups. In cause-specific hazard models on the attained-age scale, American admixed-Latino (hazard ratio, 1.30; 95% CI, 1.14-1.47) and East Asian (hazard ratio, 1.43; 95% CI, 1.06-1.94) ancestry had higher age-specific CRC hazard than European ancestry, with consistent findings on the subdistribution scale accounting for competing death. The multiethnic XGBoost model performed best (receiver operating characteristic area under the curve, 0.898; 95% CI, 0.882-0.912; precision-recall area under the curve, 0.338; 95% CI, 0.296-0.379) and was well calibrated. CONCLUSIONS AND RELEVANCE: In this cohort study, genetic ancestry was associated with meaningful differences in CRC burden and age-specific risk. These findings suggest that a multiethnic XGBoost model may complement CRC screening as a risk-enrichment tool.

Aged↗

PubMed2026

The presence or absence of standard modifiable cardiovascular risk factors in patients with myocardial infarction impacts long-term but not 30-day mortality: a UK Biobank prospective cohort study.

AIMS: Prior studies reported higher early mortality after acute myocardial infarction (MI) in patients without standard modifiable cardiovascular risk factors (SMuRFs), warranting further validation. We aimed to evaluate whether SMuRF-absence is associated with increased 30-day cardiovascular mortality following MI. METHODS AND RESULTS: We conducted a population-based cohort study using UK Biobank data (n = 487 177). Incident MI cases occurring between 2006 and 2022 were identified through linkage to hospital and death registries. Standard modifiable cardiovascular risk factors (diabetes, hypertension, hypercholesterolaemia, current smoker) were defined at baseline and continuously assessed until MI onset. Thirty-day mortality following MI was estimated using Cox proportional hazards models, adjusted for sociodemographic, clinical, and cardiogenomic variables, were used to estimate 30-day mortality risks. Logistic regression model was used to estimate mortality risk at 10 years post-MI. Among 15 463 patients experiencing an MI (1034 without SMuRFs), SMuRF-absence was not significantly associated with 30-day mortality (HR: 0.82, 95% CI: 0.65-1.04, P = 0.103). Propensity score-matched analyses supported these findings (HR: 0.95, 95% CI: 0.69-1.29, P = 0.729). Further analyses stratified by distinct time intervals (2006-2022) revealed no significant modification of this association by advancements in acute MI management. Interaction analyses indicated no significant effect modification by sex, age, socioeconomic status, or period of MI occurrence. However, extended analysis to 10 years revealed that SMuRF absence was significantly associated with lower long-term mortality (OR: 0.61, 95% CI: 0.49-0.75, P < 0.01). CONCLUSION: In this population-based cohort, SMuRF status significantly impacted long-term but not short-term mortality following MI, indicating early survival is predominantly driven by acute-phase factors rather than baseline cardiovascular risk profiles.

Humans↗

PubMed2026

Oncotype DX-guided vs physician-directed chemotherapy and survival in HR+/HER2- breast cancer.

BACKGROUND: Oncotype DX testing guides adjuvant chemotherapy decisions in early-stage hormone receptor-positive/HER2-negative breast cancer, but testing is not universally performed, and outcomes associated with genomic-informed versus clinicopathologic-based chemotherapy decision pathways remain unclear. METHODS: Using the 2022 National Cancer Database Breast Participant User File, we identified women diagnosed from 2010 to 2022 with pathologic T1b-T2, node-negative, hormone receptor-positive/HER2-negative invasive breast cancer who received adjuvant chemotherapy and endocrine therapy. Patients were classified into an Oncotype-guided group, defined by Oncotype DX testing with a recurrence score of 26 or higher, and a physician-directed group, defined by receipt of chemotherapy without genomic testing. The primary outcome was overall survival. Analyses used multivariable Cox models, logistic-IPTW and MLP-IPTW, restricted mean survival time analysis, and a Bayesian latent confounding survival model. RESULTS: Among 56,625 women, 27,278 were in the Oncotype-guided group and 29,347 in the physician-directed group. Median ages were 59 and 56 years, respectively. The Oncotype-guided group had more favorable overall survival than the physician-directed group in multivariable Cox analysis (HR, 0.906; 95% CI, 0.856-0.959; P < 0.001), with similar findings in IPTW analyses. The association was concentrated among patients aged 56 years or older (HR, 0.866; 95% CI, 0.809-0.927; P < 0.001). The Bayesian model showed no strong residual confounding signal. CONCLUSIONS: Among chemotherapy-treated women, an Oncotype-guided pathway was associated with more favorable overall survival than a physician-directed pathway, particularly among older patients, which indicating prognostic heterogeneity selected using genomic versus conventional clinicopathologic information.

Humans↗

PubMed2026

Unveiling the BMI Risk Threshold for Osteoarthritis: Multi-Database Causal and Nonlinear Evidence.

OBJECTIVE: To characterize the nonlinear relationship between BMI and osteoarthritis (OA), and to identify BMI thresholds that inform precise prevention strategies. METHODS: This multi-database study integrated Global burden of disease 2021, National Health and Nutrition Examination Survey 2007-2018, and Genome-Wide Association Studies. A generalized additive model was performed to visualize the BMI-OA relationship, adjusting for multiple confounders. We applied segmented logistic regression models to identify potential threshold effects and used Mendelian randomization to estimate the causal effects of BMI on OA subtypes. RESULTS: From 1990 to 2021, the age-standardized prevalence and years lived with disability rates for OA were highest in regions with high SDI. OA prevalence rose nonlinearly with BMI, with breakpoints at 24.00 and 41.58 kg/m2. Each unit increase in BMI was associated with higher odds of OA between 24.00 and 41.58 kg/m2 (OR = 1.022, 95% CI: 1.003-1.041) and above 41.58 kg/m2 (OR = 1.055, 95% CI: 1.022-1.090). Women and individuals aged ≥ 45 years exhibited a higher susceptibility to knee osteoarthritis. BMI was causally associated with knee osteoarthritis (OR = 1.63, 95% CI 1.50-1.77) and hip osteoarthritis (OR = 1.54, 95% CI 1.40-1.70). CONCLUSIONS: These findings suggest that OA risk awareness and weight-management strategies should begin before BMI reaches the high range, particularly among individuals with BMI exceeding 24.00 kg/m2.

Humans↗

PubMed2026

Machine learning to differentiate colonization from infection in multidrug-resistant Gram-negative bacteria: implications for further research.

PURPOSE OF REVIEW: Machine learning has emerged as a promising tool to support antimicrobial decision-making in infectious diseases. In colonized patients, distinguishing multidrug-resistant Gram-negative bacteria (MDR-GNB) colonization from true infection remains a major clinical challenge, as both delayed appropriate therapy in severe infections and unnecessary broad-spectrum antimicrobial use may adversely affect patient outcomes and antimicrobial stewardship. This review discusses the current evidence on machine learning models for predicting or detecting MDR-GNB infection in colonized patients, highlights key methodological limitations of the available literature, and outlines future research priorities. RECENT FINDINGS: Current evidence specifically evaluating machine learning models beyond logistic regression in MDR-GNB-colonized patients remains limited. Overall, while machine learning may achieve encouraging discriminatory performance, important methodological limitations persist. Most notably, predictive models are frequently developed in heterogeneous populations that do not reflect the clinically relevant populations of colonized patients in which treatment decisions are made. Furthermore, improvements in predictive performance remain modest, possibly reflecting limited sample sizes and data granularity rather than insufficient algorithmic complexity. In our opinion, future advances could require multicenter datasets enriched with longitudinal clinical, microbiological, and genomic information, together with automated feature extraction from electronic health records. SUMMARY: The main challenge for machine learning in predicting MDR-GNB infection in colonized patients may lie not in developing increasingly sophisticated algorithms, but in generating clinically representative datasets and adopting rigorous methodological standards for model development, validation, calibration, and implementation. Future research should prioritize clinically meaningful target populations and demonstrate improvements in patient outcomes and antimicrobial stewardship beyond conventional measures of predictive performance.

antimicrobial resistance↗