Tag: pubmed

G3 (Bethesda). 2025 Sep 15:jkaf212. doi: 10.1093/g3journal/jkaf212. Online ahead of print.

ABSTRACT

F1 populations are widely used in genetic mapping studies in agriculture, where known pedigrees enable rigorous quality control measures such as segregation distortion testing. However, conventional tests for segregation distortion are inadequate for polyploids, as they fail to account for double reduction, preferential pairing, and genotype uncertainty, leading to inflated type I error rates. Prior work developed a statistical framework to address these issues in tetraploids. Here, we extend these methods to higher even ploidy levels and introduce additional strategies to mitigate the influence of outliers. Through extensive simulations, we demonstrate that our tests maintain appropriate type I error control while retaining power to detect true segregation distortion. We further validate our approach using empirical data from a hexaploid mapping population. Our methods are implemented in the segtest R package, available on the the Comprehensive R Archive Network (https://doi.org/10.32614/CRAN.package.segtest).

PMID:40971889 | DOI:10.1093/g3journal/jkaf212

Clin Orthop Relat Res. 2025 Sep 17. doi: 10.1097/CORR.0000000000003682. Online ahead of print.

ABSTRACT

BACKGROUND: Prior studies have reported that imaging evaluation of osseous morphology in femoroacetabular impingement (FAI) is best performed with CT, which exposes patients to ionizing radiation. In recent years, a number of studies have evaluated whether various novel MRI protocols, which do not expose patients to ionizing radiation, can effectively assess osseous morphology in patients with FAI. Our institution incorporated in- and out-of-phase sequences into a routine MRI protocol to better assess acetabular version; however, it is unknown how in- and out-of-phase MRI compares with CT imaging in FAI evaluation.

QUESTIONS/PURPOSES: (1) How reliably do acetabular version measurements taken from in- and out-of-phase MRI agree with acetabular version measurements taken from CT imaging? (2) How similar are hip morphometric measurements taken from routine MRI sequences as compared with hip morphometric measurements taken from hip-specific CT?

METHODS: We conducted a retrospective electronic medical record review of the patients of two attending sports medicine orthopaedic surgeons from May 2014 to May 2024 who were evaluated for symptomatic hips. It is the general practice of these surgeons to obtain both hip-specific CT scans and in- and out-of-phase MRI for patients with suspected FAI. Patients were included if they had a diagnosis of FAI, were older than 12 years of age, underwent hip-specific morphometric CT scanning and in- and out-of-phase MRI of the affected side, and had imaging interpretation performed by fellowship-trained musculoskeletal radiologists at our institution. Hip morphometric measurements were retrospectively recorded from prospectively interpreted radiology reports. Our initial chart review yielded 178 patients (188 hips) with a diagnosis of FAI who underwent both CT and MRI imaging. After the application of inclusion and exclusion criteria, 30 patients (33 hips) lacked an in- and out-of-phase MRI, 11 patients (11 hips) had the imaging performed on contralateral hips, and 42 patients (44 hips) lacked complete morphometric measurements, yielding 95 patients (100 hips) who were included in our study. Our study population comprised 72% (68 of 95) females with a mean ± SD age of 29 ± 9 years and BMI of 25.3 ± 4.7 kg/m2. Of those included, 56 patients had their measurements confirmed by our institution’s fellowship-trained musculoskeletal radiologists to assess for intrarater and interrater reliability. The assessed morphometric measurements included: midcoronal angle, midsagittal angle, alpha angle, femoral neck angle, and femoral neck version at the 1, 2, and 3 o’clock positions. These measurements were statistically compared with intraclass correlation coefficients (ICCs) to assess intermodality measurement agreement and thus determine the reliability between in- and out-of-phase MRI and CT. Each morphometric measurement also underwent t-tests to determine the similarity in measurements between in- and out-of-phase MRI and hip-specific CT sequences.

RESULTS: Acetabular version measurements taken from the unique sequences of in- and out-of-phase MRI demonstrated ICCs of 0.62, 0.67, and 0.80 at 1, 2, and 3 o’clock, respectively. Other morphometric measurements with standard MRI sequencing demonstrated ICCs ranging from a low of 0.41 (poor) for femoral neck angle to a high of 0.73 (moderate) for femoral version. Higher ICCs demonstrate moderate to good agreement between imaging modalities for acetabular version measurements with unique axial sequences of in- and out-of-phase MRI and CT scans. ICC values comparing measurements from routine MRI protocol and CT scans demonstrate poor to moderate agreement in morphometric measurements between imaging modalities. This indicates a reliable agreement in morphometric measurements between in- and out-of-phase MRI and CT and less reliability in agreement for measurements made with routine MRI.

CONCLUSION: The in- and out-of-phase MRI protocol had moderate to good reliability in correlation to CT for evaluating acetabular version in patients with FAI. Hip osseous and soft tissue evaluation may be effectively achieved using in- and out-of-phase MRI axial sequences in addition to routine hip MRI sequences. Surgeons who perform hip arthroscopy may consider being more selective in using CT for evaluating FAI. Future research may incorporate additional MRI sequences to better evaluate FAI hip morphometric measurements.

LEVEL OF EVIDENCE: Level IV, diagnostic study.

PMID:40971886 | DOI:10.1097/CORR.0000000000003682

Clin Orthop Relat Res. 2025 Sep 17. doi: 10.1097/CORR.0000000000003679. Online ahead of print.

ABSTRACT

BACKGROUND: Numerous clinical risk factors and moderate heritability have been reported for meniscus injury. However, the genetic etiology of meniscus injury remains understudied. This study was a multiancestry genome-wide association study (GWAS) of meniscus injury aimed at identifying genomic variants that influence risk and elucidating the mechanisms by which they may exert their effects.

QUESTIONS/PURPOSES: (1) Which single nucleotide polymorphisms (SNPs), genes, and molecular pathways are associated with meniscus injury? (2) How do independent SNPs with genome-wide significance alter the expression of genes within cells related to the meniscus? (3) Can a polygenic risk score (PRS) for meniscus injury discriminate between patients with meniscus injury and controls? (4) Does obesity increase the risk of meniscus injury using a Mendelian randomization framework?

METHODS: A meta-analysis of 38,062 patients with meniscus injury and 700,343 control participants was performed using GWAS summary statistics from the NIH’s All of Us and FinnGen cohorts. All of Us provided an ancestrally diverse cohort for a multiancestry GWAS. Functional Mapping and Annotation of Genetic Variants (FUMA) and Meta-Analysis Gene-Set Mining of GWAS (MAGMA) platforms were used to identify genes of interest and perform expression quantitative trait loci and chromatin interaction mapping of SNPs with genome-wide significance. A PRS was developed for European individuals using the FinnGen GWAS and was validated on a European cohort from All of Us. Mendelian randomization assesses putative causal associations between an exposure and outcomes given random assortment of alleles during meiotic recombination and was used to analyze the risk of obesity and meniscus injury.

RESULTS: Twelve independent genome-wide significant loci (p < 5 × 10-8) were identified, and genes UQCC1, BMP6, EGR2, CAPZB, SMG6 were associated with meniscus injury after Bonferroni correction for all identified genes (p < 2.6 × 10-6). A subset of genes identified through MAGMA were enriched in the transforming growth factor-β (TGF-β) signaling pathway. Independent SNPs altered expression of genes related to the TGF-β pathway, including GDF5, BMP6, MMP24, and UQCC1. As an independent intronic SNP of UQCC1, rs2425055 was in chromosomal contact with GDF5OS in mesenchymal stem cells and decreased the expression of GDF5OS. A PRS for meniscus injury demonstrated differences in genetic risk between patients with meniscus injury and control participants (area under the curve 0.53 [95% confidence interval (CI) 0.51 to 0.54], OR per SD increase 1.10 [95% CI 1.05 to 1.15]; p = 3.34 × 10-5). Mendelian randomization demonstrated that genetic predisposition to obesity increased the risk of meniscus injury (OR 1.29 [95% CI 1.24 to 1.34]; p = 9.58 × 10-38).

CONCLUSION: The 12 independent genetic variants identified suggest a genetic contribution to meniscus injury risk across multiple ancestries. These SNPs may modulate meniscus injury risk by modifying genetic expression of key upstream regulators of the TGF-β signaling pathway (GDF5,BMP6,TGF-β2) and related genes (UQCC1,EGR2,MMP24). Although previous studies have implicated BMP6 and EGR2 in meniscus fibrochondrocyte differentiation and adaptive stress responses, our results demonstrate that genetic variation related to these genes modifies meniscus injury risk at a population level. In addition to demonstrating a putative causal relationship between obesity and meniscus injury through Mendelian randomization, we present a validated PRS that predicted risk of meniscal injury.

CLINICAL RELEVANCE: The genes related to meniscus injury identified in this GWAS are promising therapeutic targets for studies on meniscus regeneration. Our validated PRS presents an opportunity to develop screening and prevention strategies for individuals at high risk of meniscus injury.

PMID:40971882 | DOI:10.1097/CORR.0000000000003679

PLoS One. 2025 Sep 19;20(9):e0332237. doi: 10.1371/journal.pone.0332237. eCollection 2025.

ABSTRACT

BACKGROUND: Acute Myeloid Leukemia (AML) accounts for 20-25% of all leukemia diagnosed worldwide. According to Globoccan 2020, leukemia ranked the 15th most prevalent cancer with an estimated 474,519 new cases and 311,594 deaths annually. However, due to scarcity of well documented cancer registries, epidemiological and survival data of patients with AML is lacking in many African countries, including Tanzania. Therefore, the primary objective of this study was to determine the clinical features, laboratory characteristics and survival outcomes of AML patients treated with different regimens in Tanzania.

METHODS: Data from all adult patients diagnosed with AML at Muhimbili National Hospital (MNH) between January 2018 and December 2023 were analyzed in this retrospective study. STATA version 16 was used for data analysis. The survival outcome was calculated using the Kaplan-Meier method. To evaluate the statistical significance of the results, a p-value cut-off of 0.05 was used. The Cox proportional hazards model was used to identify predictors of survival and to estimate the effect of covariates on the hazard of death. Kruskal Wallis was used to compare the median values for laboratory results and pairwise comparison of median laboratory values was done using the Dunn Test.

RESULTS: A total of 245 patients were diagnosed with acute leukemia during the five-year period (2018-2023), of which 169 (68%) had AML. The mean age at diagnosis was 47.2 (SD ± 18.5) years. Majority of the patients were females (60.7%), and had de novo AML. Most of the patients presented with symptoms of anemia (98.2%) and fever (79.5%). The median survival time was 81 days with a one-year overall survival probability of 15.2%. Patients that resided outside of the Dar es Salaam region had a 74% increase hazard of mortality compared to those living within the Dar es Salaam region (aHR: 1.74, 95% CI: 1.15-2.64, p = 0.008). Patients receiving any form of chemotherapy had a 39% lower hazard of mortality compared to those who were on supportive treatment alone (aHR: 0.61, 95% CI: 0.40-0.93, p = 0.022).

CONCLUSION: AML is the most common acute leukemia among adults in Tanzania, primarily affecting young females under 50 years. Resource constraints and limited treatment options result in poor outcomes, with a median survival of 81 days and one-year overall survival of 15.2%.

PMID:40971875 | DOI:10.1371/journal.pone.0332237

Br J Radiol. 2025 Sep 15:tqaf225. doi: 10.1093/bjr/tqaf225. Online ahead of print.

ABSTRACT

OBJECTIVES: This study evaluated three LLM chatbots (GPT-3.5-turbo, GPT-4-turbo, and GPT-4o) on their effectiveness in supporting patient education by answering common patient questions for CT, MRI, and DSA informed consent, assessing their accuracy and clarity.

METHODS: Two radiologists formulated 90 questions categorized as general, clinical, or technical. Each LLM answered every question five times. Radiologists then rated the responses for medical accuracy and clarity, while medical physicists assessed technical accuracy using a Likert scale. semantic similarity was analyzed with SBERT and cosine similarity.

RESULTS: Ratings improved with newer model versions. Linear mixed-effects models revealed that GPT-4 models were rated significantly higher than GPT-3.5 (p < 0.001) by both physicians and physicists. However, physicians’ ratings for GPT-4 models showed a significant performance decrease for complex modalities like DSA and MRI (p < 0.01), a pattern not observed in physicists’ ratings. SBERT analysis revealed high internal consistency across all models. SBERT analysis revealed high internal consistency across all models.

CONCLUSION: Variability in ratings revealed that while models effectively handled general and technical questions, they struggled with contextually complex medical inquiries requiring personalized responses and nuanced understanding. Statistical analysis confirms that while newer models are superior, their performance is modality-dependent and perceived differently by clinical and technical experts.

ADVANCES IN KNOWLEDGE: This study evaluates the potential of LLMs to enhance informed consent in radiology, highlighting strengths in general and technical questions while noting limitations with complex clinical inquiries, with performance varying significantly by model type and imaging modality.

PMID:40971869 | DOI:10.1093/bjr/tqaf225

Rev Esc Enferm USP. 2025 Sep 8;59:e20250182. doi: 10.1590/1980-220X-REEUSP-2025-0182en. eCollection 2025.

ABSTRACT

OBJECTIVE: This study aimed to determine the factors relating to climate change anxiety in women at reproductive age.

METHOD: This study is descriptive and cross-sectional. This study included 351 women aged 18-45 years. Data were collected via face to face interviews using the ‘Women’s Descriptive Characteristics and Climate Change Perception Assessment Form’ and ‘Climate Change Anxiety Scale for Women’s Health’ between June and October 2024 at a family health center in Mersin province of Türkiye. Data analysis included descriptive statistical methods and chi-squared automatic ınteraction detector analysis.

RESULTS: The average age of the women was 27.91 ± 8.30 years (n = 351). The Climate Change Anxiety Scale for Women’s Health mean score was 52.46 ± 17.19. Women’s experience of anxiety regarding the negative consequences of climate change affected the scale and all sub-dimensions (physiological health, behavior, and gender) (p < 0.05).

CONCLUSION: Health professionals should provide information and assessments including the effects of climate change on health in care services. They should plan interventions to reduce women’s anxiety levels towards climate change.

PMID:40971202 | DOI:10.1590/1980-220X-REEUSP-2025-0182en

JMIR Hum Factors. 2025 Sep 19;12:e72749. doi: 10.2196/72749.

ABSTRACT

BACKGROUND: Smoking remains a leading cause of death worldwide, with young adults particularly at risk due to the lack of targeted cessation initiatives. While mobile apps show promise in supporting smoking cessation, they primarily target smokers already motivated enough to install them, highlighting the need for interventions that reach those who are not yet ready to take that step.

OBJECTIVE: This paper focuses on designing and evaluating Smokwit, a digital smoking cessation intervention aimed at young adults during the act of smoking. Smokwit seeks to investigate the early stages of smoking cessation (precontemplation and contemplation) that are important yet rarely investigated.

METHODS: The paper is based on the design science research methodology where a digital intervention-Smokwit-was designed and evaluated in the wild using a mixed method approach combining quantitative results of a quasi-experiment with qualitative insights from users and experts. More specifically, Smokwit is a novel gamified ambient intervention that integrates a connected ashtray with a mobile app. The ashtray aims to trigger processes of change, in particular consciousness raising and social liberation (as part of the transtheoretical model of change) by provoking curiosity, self-reflection, and ad-hoc peer discussions among smokers. The linked mobile app is designed to reinforce this goal by providing smoking cessation self-help material and coaching possibilities. We evaluated the effectiveness of this intervention through a 3-month field study designed as a quasi-experiment with a treatment and control group (n=46). A qualitative analysis with users (n=10) and smoking cessation experts (n=7) provides insights into the type of interactions that happened within and outside the system as well as practical implications for smoking cessation organizations.

RESULTS: The qualitative findings revealed that the intervention promoted smokers’ self-reflection, peer discussions, and mobile app interactions. Furthermore, the quantitative analysis uncovered a possible trend toward increased readiness to quit among smokers in the treatment group compared to the control group; however, this did not reach conventional levels of statistical significance (b=1.33; z=1.91; P=.06).

CONCLUSIONS: Smokwit provides encouraging insights into how to design a bottom-up digital intervention that targets young adults at an opportune moment to support them on their smoking cessation journey.

PMID:40971186 | DOI:10.2196/72749

Epilepsia. 2025 Sep 19. doi: 10.1111/epi.18633. Online ahead of print.

ABSTRACT

This study was undertaken to systematically evaluate the efficacy of cell therapy in reducing seizures in animal models of chronic epilepsy. Three databases, Ovid MEDLINE, Ovid Embase, and Web of Science, were searched using predetermined eligibility criteria. The relevant preclinical controlled studies were included for review and meta-analysis using a random-effects model to calculate summary estimates of the effect size (percentage reduction in seizures). The degree of heterogeneity among the included studies was assessed using the I² statistic. Subgroup meta-analysis and meta-regression were performed to further elucidate the sources of heterogeneity. Thirty published studies met the eligibility criteria, including a total of 1306 animals. The majority of studies used kainic acid and pilocarpine status epilepticus models of mesial temporal lobe epilepsy (MTLE). The random effects model revealed an overall reduction in seizure frequency of 54.8% (95% confidence interval = 48.0558-61.5455) compared to the control, and the heterogeneity was 87.1% among the included studies. The meta-regression revealed that seven study characteristics significantly accounted for the between-study heterogeneity. They can be grouped into three broad categories: epilepsy-specific, animal-specific, and cell transplantation-specific. The greatest seizure reduction was observed in the post-kainic acid status epilepticus model of chronic MTLE, when the cells were delivered intravenously and when the seizure reduction was measured as seizure frequency. Embryonic stem cell transplantation showed the greatest efficacy in reducing seizures. Cell transplantation shows favorable efficacy as a treatment that can reduce seizure recurrence in chronic animal models of epilepsy. High heterogeneity between studies reflects the diverse methodologies employed in preclinical research on cell therapy for epilepsy. Despite these encouraging findings, the high risk of publication bias and variability in study design emphasize the need for further robust preclinical studies to confirm these reported outcomes.

PMID:40971184 | DOI:10.1111/epi.18633

JAMA Health Forum. 2025 Sep 5;6(9):e253192. doi: 10.1001/jamahealthforum.2025.3192.

ABSTRACT

IMPORTANCE: Subspecialists-physicians with narrower clinical focus-play an increasing role in US health care, particularly in surgery, where most trainees now pursue fellowship training. Yet little is known about the degree of subspecialization among practicing surgeons and the evolving role of surgical generalists.

OBJECTIVE: To quantify trends in surgical subspecialization and examine the geographic distribution of subspecialists and the procedural scope of surgical generalists.

DESIGN, SETTING, AND PARTICIPANTS: A retrospective cohort study using 100% Medicare Part B data from 2000, 2010, and 2021, including all fee-for-service beneficiaries treated by physicians in general surgery, neurosurgery, ophthalmology, orthopedic surgery, and otolaryngology was caried out. A novel classification method combining k-means clustering, large language models, and expert validation to distinguish subspecialists from surgical generalists based on procedural claims was used. The analysis was undertaken in 2023 and 2024.

MAIN OUTCOMES AND MEASURES: The number of distinct subspecialties, the share of subspecialists in each surgical specialty, their geographic distribution across hospital referral regions (HRRs), and the association between subspecialist supply and procedural diversity among generalists.

RESULTS: Overall, more than 70 000 surgeons were included. The share of subspecialists increased from 38% in 2000 to 58% in 2021, reflecting the growth of recognized subspecialties (from 24 to 33) and expansion of existing ones. Subspecialization rates varied by specialty, rising from 9% to 28% in otolaryngology and from 66% to 77% in neurosurgery. While subspecialist supply per 100 000 fee-for-service beneficiaries remained stable, the mean number of surgical generalists per 100 000 declined from 105 to 50. A 10% increase in subspecialist supply in an HRR was associated with a 0.94% decrease (95% CI, -0.15% to -0.41%) in the number of unique procedures performed by generalist surgeons.

CONCLUSIONS AND RELEVANCE: This cohort study found that subspecialization has considerably reshaped the surgical workforce, concentrating care among subspecialists while narrowing the procedural scope of generalist surgeons. These shifts raise concerns about access to generalist care, particularly in regions with declining generalist supply, and suggest the need for policies that consider both specialization and geographic equity in surgical workforce planning.

PMID:40971167 | DOI:10.1001/jamahealthforum.2025.3192

JAMA Health Forum. 2025 Sep 5;6(9):e253489. doi: 10.1001/jamahealthforum.2025.3489.

ABSTRACT

IMPORTANCE: Overdoses involving methamphetamines and cocaine have increased in recent years. Identification of individuals at highest risk could facilitate the implementation of evidence-based interventions to reduce overdose risk.

OBJECTIVE: To develop and internally validate a model that predicts hospitalization or emergency department (ED) treatment for stimulant-involved overdose among the Medicaid-insured population.

DESIGN, SETTING, AND PARTICIPANTS: This was a retrospective case-cohort study using Medicaid claims data from 2016 to 2019 (development) and 2020 (validation) for all Medicaid enrollees age 15 years or older with a cocaine- or other stimulant-involved overdose. A subcohort was created using a simple random sample of the full cohort of all cases. Within the full cohort, cases were identified as those having any inpatient or ED encounter for stimulant-involved overdose during the following year. A case-cohort sample was obtained for each calendar year from 2016 to 2020, each with a subcohort size of 100 000. Each individual contributed only 1 case event (for an individual with multiple overdoses, only the first eligible was selected). For each of the 4 overdose outcomes, a predictive weighted Cox model was first developed among enrollees of sampling years 2016 to 2019 (development set), and its performance was evaluated in our test set of 2020. The prediction models were first developed in November 2023, and the model fairness assessment was performed in April to May 2025.

INTERVENTIONS OR EXPOSURES: Individual-level candidate predictors were demographic characteristics, enrollment, health care utilization, and other clinical variables. Area-level variables included social, economic, housing, and demographic characteristics data from the American Community Survey, rural-urban classification, Social Deprivation Index, retail opioid dispensing rates, and health resources.

MAIN OUTCOMES AND MEASURES: Four types of stimulant-involved overdose associated with hospitalization or ED treatment: cocaine-involved overdose, (1) involving an opioid or (2) not involving an opioid; or methamphetamine-, ecstasy-, or other psychostimulant-involved overdose (hereafter, other stimulant), (3) involving an opioid or (4) not involving an opioid.

RESULTS: The analysis included 78 795 enrollees with cocaine- and other stimulant-involved overdose (mean [SD] age, 42.2 [13.7] years; 33 304 [42%] female and 45 491 [58%] male individuals). Weighted Cox regression prediction models showed good calibration and high discriminatory performance (Harrell C statistic): cocaine-involved overdose, with (0.923) or without (0.902) an opioid; other stimulant-involved overdose, with (0.909) or without (0.868) an opioid. For cocaine-involved overdose with opioids, previous individual opioid use disorder diagnosis or cocaine use disorder diagnosis played the largest role in overdose risk prediction. For cocaine-involved overdose without opioids, previous cocaine use disorder diagnosis and area-level income inequality and housing variables contributed most to prediction. For other stimulant-involved overdose with opioids, previous opioid use disorder diagnosis and area-level percentage of those living with a disability contributed most to prediction. For other stimulant-involved overdoses without opioids, previous stimulant-related disorder and area-level proportion of individuals receiving Supplemental Nutrition Assistance Program contributed most to prediction.

CONCLUSIONS AND RELEVANCE: This case-cohort study found that readily available data can be used to identify those at high risk of hospitalization or ED visit for cocaine- or stimulant-involved overdose. These individuals would likely benefit most from evidence-based interventions and awareness of risk factors for overdose.

PMID:40971166 | DOI:10.1001/jamahealthforum.2025.3489