Nevin Manimala

Arch Pathol Lab Med. 2025 Nov 27. doi: 10.5858/arpa.2025-0472-CP. Online ahead of print.

ABSTRACT

CONTEXT.—: Optical genome mapping (OGM) represents a promising cytogenomic technology that detects structural variants, including fusions, rearrangements, copy number variants, and loss of heterozygosity, in a single assay. Unlike karyotyping, fluorescence in situ hybridization, or chromosomal microarray, OGM leverages long-molecule imaging to map the whole genome with high resolution. This positions OGM as a novel tool for constitutional and somatic/cancer genomics. However, its current and planned utilization in clinical and research settings remains unknown, necessitating further investigation.

OBJECTIVE.—: To investigate the current utilization of OGM in clinical and research laboratories, assess its applications, and evaluate future utilization strategies.

DESIGN.—: In 2024, a supplemental questionnaire was incorporated into 6 College of American Pathologists proficiency testing programs to evaluate OGM’s utilization.

RESULTS.—: Of 921 returned questionnaires, 712 were analyzed after duplicates were removed. Sixty-seven (9.4%) currently offered OGM testing: 5.2% (37) for research only, 1.8% (13) for only clinical use, and 2.4% (17) for both. Future adoption plans showed 7.6% (53 of 700 laboratories) and 7.9% (55 of 700 laboratories) aiming to implement OGM clinically within 12 and 24 months, respectively. The most common applications included hematologic malignancies and constitutional/germline postnatal disorders, followed by prenatal testing. International laboratories demonstrated statistically higher utilization rates than domestic laboratories (P = .001).

CONCLUSIONS.—: This first survey on OGM clinical utilization reveals its status as a niche technology, with 67 laboratories currently using it. Its primary clinical applications are in constitutional/germline analysis and hematologic malignancies. Although international laboratories led in 2024, 108 laboratories (domestic and international) plan clinical adoption within 24 months, signaling OGM’s potential for broader integration.

PMID:41308031 | DOI:10.5858/arpa.2025-0472-CP

Cancer Med. 2025 Dec;14(23):e71316. doi: 10.1002/cam4.71316.

ABSTRACT

INTRODUCTION: Thyroid cancer is one of the most common cancers in adolescents and young adults (AYA, 15 to 39 years), with an excellent 5-year survival of 98%. However, treatments for thyroid cancer such as radioactive iodine and thyroid hormone suppression may increase the risk for multiple late effects (LEs). We investigated the incidence of severe LE that clustered in AYA thyroid cancer survivors in a large population-based cohort.

METHODS: California and Utah Cancer Registry records identified AYAs diagnosed with first thyroid cancer during 2006-2018 linked to statewide hospitalization, ambulatory surgery, and emergency department data. Cohort entry began 2 years from diagnosis. Severe LE included cardiovascular, respiratory, renal, and liver diseases, diabetes, and second cancers. Cumulative incidence of each LE, accounting for the competing risk of death, was calculated. Latent class analysis (LCA) identified clustering of LE over the study period. The number of LE classes was identified by selecting models with the lowest likelihood-ratio G² statistic, Akaike’s Information Criterion, and Bayesian Information Criterion. Probabilities of each LE are presented in each class.

RESULTS: Of 14,268 survivors, median follow-up time was 7 years. The LCA model identified 3 classes: 88% with low LEs, 9% experiencing moderate LEs with elevated probability of diabetes, liver, and respiratory conditions, and the remaining 3% experiencing the highest probability of all LEs, including cardiovascular disease. Non-Hispanic (nH)-Black and Hispanic survivors, those on public insurance, residing in lower socioeconomic status neighborhoods, or diagnosed with distant stage disease experience greater odds of being in the moderate and cardiovascular classes.

CONCLUSION: While most survivors of AYA thyroid cancer have a low incidence of LEs, a small proportion have a high probability of multiple morbidities. Multidisciplinary survivorship care should include identifying and supporting thyroid cancer survivors at higher risk for developing multiple LEs through early screening.

PMID:41308028 | DOI:10.1002/cam4.71316

J Med Internet Res. 2025 Nov 27;27:e74149. doi: 10.2196/74149.

ABSTRACT

BACKGROUND: Nurse-led telecare consultations have emerged as a promising approach for the long-term management of stroke survivors, particularly in the context of COVID-19 pandemic-related disruptions. While several studies have explored its use, the effectiveness of nurse-led telecare consultations in post-acute stroke care remains unclear.

OBJECTIVE: This study aimed to evaluate the effectiveness of nurse-led telecare consultation for poststroke management among stroke survivors who were discharged from the hospital and lived in the community.

METHODS: A systematic search was conducted across 6 databases-CINAHL, MEDLINE, PsycINFO, PubMed, Embase, and CENTRAL-for randomized controlled trials published from inception to February 2025. Included studies examined nurse-led telecare consultations compared to usual care among stroke survivors living in the community. Studies involving individuals who were hospitalized or institutionalized were excluded, along with reviews, abstracts without full texts, non-English or non-Chinese articles, and studies not meeting the criteria for randomized controlled trials. Primary and secondary outcomes included blood pressure (BP), psychological burden, quality of life, medication adherence, health care service use, stroke recurrence, survivor functioning, and coping. Continuous outcomes were analyzed using mean differences (MDs) or standardized MDs with 95% CIs under a random-effects model and dichotomous outcomes using odds ratios with 95% CIs via the Mantel-Haenszel method. Heterogeneity was assessed using the chi-square test and I² statistics.

RESULTS: In total, 9 studies involving 2524 participants were included. Ischemic stroke was the most common type (n=1568, 62.13%) of stroke. Meta-analysis showed that nurse-led telecare significantly increased the likelihood of achieving target BP (odds ratio 2.33, 95% CI: 1.83-2.98; P<.001). For continuous outcomes, pooled analyses showed nonsignificant but directionally favorable reductions in systolic BP (MD -4.83, 95% CI -12.51 to 2.85; I² =92%), diastolic BP (MD -6.41, 95% CI -13.76 to 0.93; I²=97%), and low-density lipoprotein cholesterol (MD 0.01, 95% CI -0.08 to 0.09; I²=97%). Heterogeneity was substantial for several key outcomes (I²>90% for systolic BP and diastolic BP). Some outcomes, such as medication adherence and stroke recurrence, were reported by only 1 (11.11%) study. Additional benefits were observed in coping ability and reduced hospital readmissions, but findings for psychological well-being and quality of life were mixed.

CONCLUSIONS: Nurse-led telecare consultations may support better BP management and coping and reduce hospital readmissions among community-dwelling stroke survivors. However, the pooled effects for continuous outcomes were inconclusive, and heterogeneity remained high. Therefore, these findings should be interpreted with caution, and further high-quality trials with standardized outcome measures and longer-term follow-up are warranted to confirm effectiveness.

TRIAL REGISTRATION: PROSPERO CRD42023492692; https://www.crd.york.ac.uk/PROSPERO/view/CRD42023492692.

PMID:41307946 | DOI:10.2196/74149

Augment Altern Commun. 2025 Nov 27:1-12. doi: 10.1080/07434618.2025.2588563. Online ahead of print.

ABSTRACT

This study aimed to elicit and analyze the views and preferences of a variety of AAC stakeholders regarding terminology related to augmentative and alternative communication (AAC) and the people who use or could benefit from it. We used an anonymous online survey to ask nonspeaking AAC users, speaking AAC users, relatives of AAC users, and AAC professionals their preferences on 119 English terms related to AAC, AAC users, and communication disability. The survey also collected demographic information, including age, country, connection to AAC, and disability identity. A total of 556 participants completed the survey. We aimed to determine broad terminology preferences across stakeholder groups and identify areas of disagreement between stakeholders. By making comparisons between related terms and between stakeholder groups, we were able to achieve this aim. There were statistically significant preferences between terms within all groups of related terms. Stakeholder groups also frequently disagreed with each other about AAC terminology: between-group differences in the frequency with which respondents supported, disliked, and/or were unfamiliar with terms were present for 81 of the 119 terms. The preferences uncovered in this study can support respectful language guidance around AAC. Further work should ideally address terminology preferences among stakeholder samples that are less focused on the United States, more focused on marginalized cultural groups, include stakeholders with more limited language skills, and/or address terminology in languages other than English.

PMID:41307945 | DOI:10.1080/07434618.2025.2588563

Clin Infect Dis. 2025 Nov 27:ciaf655. doi: 10.1093/cid/ciaf655. Online ahead of print.

ABSTRACT

BACKGROUND: Clinical heterogeneity in Staphylococcus aureus bacteremia (SAB) complicates clinical management and research. We have previously identified five clinically distinct subphenotypes of SAB associated with differences in outcomes and response to adjunctive rifampicin. Here, we aimed to identify these subphenotypes in geographically diverse observational cohorts, including a higher prevalence of methicillin-resistant S. aureus (MRSA) bacteremia and the USA300 clone.

METHODS: We studied three cohorts of adults with SAB from observational studies: a UK retrospective study (Edinburgh cohort 2, n=463); a Dutch prospective study (IDISA, n=490); and a USA prospective study (SABG-PCS, n=755). Subphenotypes were identified from routinely available clinical data using latent class analysis.

RESULTS: Patients from the SABG-PCS cohort had greater multimorbidity and more MRSA bacteremia (40.2%, 303/755), including infection with the USA300 clone (14.7%, 111/755). Five distinct subphenotypes were identified in each cohort: (A) older age and cardio-metabolic multimorbidity; (B) nosocomial acquisition and intravenous catheter portal of entry; (C) community acquisition and metastatic infection; (D) chronic kidney disease; and (E) younger age, injection drug use, and metastatic infection. Bacterial genotypes varied substantially between the Edinburgh 2 and SABG-PCS cohorts but did not differ between subphenotypes within each cohort. 90-day mortality was highest in subphenotype A, and persistent bacteremia in subphenotypes C and E.

CONCLUSIONS: We have reproducibly identified five clinical subphenotypes of SAB in observational cohorts including diverse bacterial genetic lineages and a cohort with a high prevalence of MRSA and USA300 bacteremia. These robustly reproducible clinical subphenotypes provide a framework to rationalize the heterogeneity intrinsic to SAB.

PMID:41307923 | DOI:10.1093/cid/ciaf655

J Glob Health. 2025 Nov 28;15:04354. doi: 10.7189/jogh.15.04354.

ABSTRACT

BACKGROUND: Ovarian cancer (OC) has the worst prognosis and highest death rate of all gynaecological cancers in the USA. We examined the independent effects of individual-, neighbourhood-, and state-level factors on ovarian cancer incidence using a multilevel analytical framework.

METHODS: In this retrospective cohort study, we analysed de-identified data from the All of Us research database, identifying women ≥18 years without prior ovarian cancer before January 2017. Participants were followed from 1 January 2017 through October 2023 (median follow-up: 6.6 years). Mixed-effects Cox regression models examined data on 85 388 individuals nested within ZIP-code areas and states, analysing individual-level risk factors and neighbourhood-level socioeconomic determinants, while accounting for geographic clustering. We fitted four progressive models: a null (random effects only), individual-level factors, neighbourhood-level factors, and full model with all covariates.

RESULTS: Among 85 388 women followed for a total of 569 847 person-years, 419 (0.49%) developed OC. Age demonstrated the strongest associations, with significantly elevated risks of developing OC among women aged 50-59 years (adjusted hazard ratio (aHR) = 1.83; 95% confidence interval (CI) = 1.28-2.61), 60-69 years (aHR = 2.01; 95% CI = 1.39-2.90), and ≥70 years (aHR = 1.67; 95% CI = 1.07-2.59) compared to those <40 years. Retired women had increased risk of OC compared to employed women (aHR = 1.39; 95% CI = 1.04-1.86). Non-Hispanic Black women demonstrated lower risk of OC than non-Hispanic White women (aHR = 0.63; 95% CI = 0.45-0.88). Regional variations showed 53% lower risk in the South vs. Northeast (aHR = 0.47; 95% CI = 0.25-0.86). Hormone replacement therapy was associated with increased risk of OC (aHR = 2.46; 95% CI = 1.07-5.67). Significant geographic clustering of OC was observed at neighbourhood and state levels.

CONCLUSIONS: Individual-level factors, particularly age and employment status, are the primary determinants of OC risk, while apparent geographic disparities reflect population composition, rather than unmeasured environmental factors. The complete explanation of geographic clustering through measured covariates could provide important insights for targeted prevention strategies and future epidemiological research.

PMID:41307908 | DOI:10.7189/jogh.15.04354

J Glob Health. 2025 Nov 28;15:04350. doi: 10.7189/jogh.15.04350.

ABSTRACT

BACKGROUND: Diarrhoea among children under five years old (i.e. childhood diarrhoea) causes significant morbidity and mortality in low and middle-income countries (LMICs). We conducted this systematic review and meta-analysis to quantify the proportion of childhood diarrhoea attributable to Campylobacter spp., diarrhoeagenic Escherichia coli (E. coli), Salmonella spp., and Shigella spp. in LMIC settings.

METHODS: We included epidemiological studies published between 2000 and 2025, and extracted data on study location, sample size, and pathogen-specific parameters. Two reviewers independently performed database searches, publication screening, data extraction, and quality assessment, with any conflicts resolved by a third reviewer. We reported the results of the meta-analysis as pooled proportions (positive samples divided by the total samples tested for each enteropathogen) and 95% confidence intervals. We assessed all potential sources of heterogeneity using univariable and multivariable meta-regression, quantified moderator contributions as pseudo-R² values based on reductions in τ², and tested for interaction effects. We also evaluated robustness through leave-one-out analyses, sequentially excluding individual studies to examine their influence on pooled estimates and heterogeneity.

RESULTS: We included 71 records encompassing 84 studies. Pooled proportions were 8.6% for Campylobacter spp., 23.0% for diarrhoeagenic E. coli (DEC), 2.6% for Salmonella spp., and 8.8% for Shigella spp., with wide variation across studies. Subgroup analyses showed higher proportions of Campylobacter spp. and Shigella spp. in Asia and with polymerase chain reaction-based detection, and greater DEC proportions in America and Africa. Salmonella spp. remained low across regions and study designs. Year- and country-specific analyses showed no consistent temporal trends, though DEC peaked in 2014 (77.9%, two studies) and Shigella spp. was higher in 2020 (20.7%, ten studies), both driven by a limited number of studies.

CONCLUSIONS: Standardising diagnostic methods and study designs is essential for reducing heterogeneity and improving the reliability of pooled proportion estimates in epidemiological research on enteric pathogens. Improving water supply, sanitation, hygiene, and food safety remains crucial for reducing the burden of childhood diarrhoea in LMICs.

PMID:41307907 | DOI:10.7189/jogh.15.04350

J Am Chem Soc. 2025 Nov 27. doi: 10.1021/jacs.5c14970. Online ahead of print.

ABSTRACT

Developing efficient strategies to copolymerize carbon dioxide (CO₂) with unsaturated hydrocarbon monomers, such as olefins, to produce CO₂-based polyesters is highly desirable but remains challenging owing to thermodynamic and kinetic barriers. Herein, we demonstrate that allenes, specifically cyclohexylallene (CA), serve as effective comonomers for one-pot copolymerization with CO₂. Using a nickel(0)-bidentate diarylphosphine complex, we achieve the statistical copolymerization of CA and CO₂ to deliver long-chain polyester P(CA-co-CO₂) with widely spaced ester linkages, via a classical sequence of oxidative addition, coordination-insertion, and reductive elimination. Systematic tuning of both phosphine ligand and solvent reveals their crucial roles in facilitating CO₂ insertion into the Ni-C bond and subsequent allene insertion into the Ni-O bond, thereby driving efficient chain propagation. Notably, incorporation of a small amount of CO₂ into the polymer backbone enhances the degradability of P(CA-co-CO₂) while preserving its high thermal stability and glass-transition temperature, compared with the allene homopolymer.

PMID:41307894 | DOI:10.1021/jacs.5c14970

Hepatol Int. 2025 Nov 27. doi: 10.1007/s12072-025-10972-7. Online ahead of print.

ABSTRACT

PURPOSE: A recent international consensus introduced revised nomenclature for steatotic liver disease (SLD). This study evaluated the impact of SLD subtypes on adverse pregnancy outcomes (apos) using updated criteria.

METHODS: In this nationwide, population-based study, we analyzed 290,527 female who underwent health check-ups within 1 year before pregnancy and delivered singleton infants. Participants were categorized into non-SLD, metabolic dysfunction-associated steatotic liver disease (MASLD), metabolic dysfunction and alcohol-related liver disease (MetALD), and alcohol-related liver disease (ALD) groups.

RESULTS: A total of 290,527 female were analyzed. Compared to female without SLD, those with MASLD (adjusted odds ratio [aOR] 2.44, 95% CI 2.33-2.55), MetALD (aOR 2.45, 95% CI 2.26-2.66) and ALD (aOR 2.28, 95% CI 2.11-2.47) had significantly higher risks of apos. These associations were observed for gestational diabetes mellitus (GDM), hypertensive disorders of pregnancy (HDP), and preterm birth. Both MASLD and ALD were associated with increased risk of low birthweight (aOR 1.15, 95% CI 1.05-1.27 and aOR 1.21, 95% CI 1.02-1.43, respectively), whereas MetALD was not (aOR 0.96, 95% CI 0.79-1.18). Due to the low incidence of placental abruption across all groups (0.3-0.5%), associations with this outcome remained inconclusive. Additionally, a higher number of cardiometabolic risk factors (CMRFs) was associated with an increased risk of apos (p for trend of odds < 0.0001).

CONCLUSION: MASLD, MetALD, and ALD were independently associated with increased risks of apos, with risk further amplified by a greater number of CMRFs. These findings underscore the importance of enhanced prenatal management for female with pre-existing SLD, particularly those with multiple CMRFs, to mitigate the risk of apos.

PMID:41307877 | DOI:10.1007/s12072-025-10972-7

Biol Trace Elem Res. 2025 Nov 27. doi: 10.1007/s12011-025-04918-1. Online ahead of print.

ABSTRACT

A large number of South American camelids (SAC) presented to a veterinary clinic are diagnosed with anemia. While various causes are known, such as infections with Haemonchus contortus, chronic inflammation, neoplasia, gastric ulcers, or deficiencies, little is known about the role of the trace elements copper and iron in SAC. In this retrospective study, the laboratory diagnostic data, in particular the red and white blood count, as well as the findings of the initial clinical examination of 181 alpacas presented at the University of Veterinary Medicine Hannover, Hannover, Germany in the period from January 2020 to September 2023 were therefore analyzed. In addition, iron, copper, transferrin, and ceruloplasmin were determined in the serum collected during the initial examination. The statistical analysis revealed significant correlations between the serum iron content and various degrees of anemia, and also between serum copper content and various degrees of anemia. These observations confirm the need to characterize the iron metabolism of SAC more precisely to improve differentiation between different causes of anemia.

PMID:41307871 | DOI:10.1007/s12011-025-04918-1