Nevin Manimala

JCO Precis Oncol. 2025 Sep;9:e2500535. doi: 10.1200/PO-25-00535. Epub 2025 Sep 17.

ABSTRACT

PURPOSE: A biomarker to help predict outcomes after prostate cancer (PCa) focal therapy would be of considerable interest. We sought to assess the association between treatment failure after focal therapy and the Decipher score, a tumor-based genomic classifier (GC).

MATERIALS AND METHODS: We performed a post hoc analysis of a single-center phase II trial (ClinicalTrials.gov identifier: NCT03503643) in which patients with unilateral grade group (GG) 2-4 PCa (n = 108) underwent hemigland cryoablation of the prostate (2017-2021; n = 108). Pretreatment biopsy tissue was subjected to transcriptomic profiling to generate GC scores. The primary outcome was the association between GC-low (<0.45) versus GC-high (≥0.45) and in-field recurrence (GG ≥2) on magnetic resonance imaging-guided biopsy 6 months post-treatment, evaluated using multivariable logistic regression.

RESULTS: In the GC-high group (n = 37), treatment failure occurred in 17 patients (46%). In the GC-low group (n = 71), treatment failure occurred in 15 patients (21%). These differences were statistically significant (odds ratio [OR], 2.61 [95% CI, 1.05 to 6.51]; P = .04). Differences at 18 months were also significant (76% v 44%; OR, 3.58 [95% CI, 1.37 to 9.36], P = .009).

CONCLUSION: In patients with PCa otherwise suitable for management with focal therapy, a high GC score (≥0.45) was independently associated with treatment failure. A GC score derived from diagnostic biopsy can be used to help predict focal therapy outcomes.

PMID:40961406 | DOI:10.1200/PO-25-00535

J Clin Oncol. 2025 Sep 17:JCO2501148. doi: 10.1200/JCO-25-01148. Online ahead of print.

NO ABSTRACT

PMID:40961402 | DOI:10.1200/JCO-25-01148

Health Aff (Millwood). 2025 Sep 17:101377hlthaff202500050. doi: 10.1377/hlthaff.2025.00050. Online ahead of print.

ABSTRACT

Although COVID-19 vaccines have been shown to be highly effective in preventing severe illness, hospitalization, and death, information on the economic benefits of COVID-19 vaccination is lacking. Using data from a comprehensive, integrated health system, we linked health plan data and electronic health records to vaccination data to compare the average medical expenditures of vaccinated versus unvaccinated patients diagnosed with COVID-19. We examined expenditures during acute (within thirty days after diagnosis) and postacute (at least thirty days after diagnosis) periods from April 2021 through July 2022. Among children, average acute medical expenditures were $194 less for vaccinated than unvaccinated cases and among adults, $1,743 less for vaccinated than unvaccinated cases. Medical expenditures in the postacute period were not statistically different by vaccination status. The findings suggest that COVID-19 vaccination is associated with lower medical expenditures in the acute period. Vaccination continues to be important for reducing the economic impact of COVID-19.

PMID:40961389 | DOI:10.1377/hlthaff.2025.00050

Neurogastroenterol Motil. 2025 Sep 17:e70160. doi: 10.1111/nmo.70160. Online ahead of print.

ABSTRACT

INTRODUCTION: Functional defecation disorders (FDD) are a prevalent etiology of refractory constipation. The diagnosis of FDD requires specific physiology testing, including anorectal manometry (ARM) and balloon expulsion test (BET). The aims of our study were to evaluate whether the complaint of painful defecation added to the Rome III symptoms questionnaire could help to differentiate subtypes of refractory chronic constipation.

MATERIALS AND METHODS: One hundred and ninety-eight constipated patients (Rome III Criteria) who had failed a 30-day fiber/laxative trial were enrolled. Before entering the study (T0) the patients underwent a digital rectal examination, including the assessment of tenderness elicited by traction of the puborectalis muscles (DRE-tenderness). Patients reporting painful defecation (occurring at least once per week) were specifically assessed at T0. Thirty days after T0, the patients underwent: DRE with DRE-tenderness evaluation. ARM + BET. Barium defecography (when ARM and BET were discordant). Colonic transit time evaluation with radiopaque markers. Based on these tests, the patients were classified into five subgroups: dyssynergic defecation (DD), inadequate defecatory propulsion (IDP), isolated structural outlet obstruction (mostly large rectocele), isolated slow transit constipation, and normal transit constipation. The association between symptoms and diagnostic outcomes was assessed using multivariate analysis based on binary logistic regression.

RESULTS: Eighty-one patients (40.9%) reported weekly episodes of painful defecation, while 86 patients (43.3%) reported DRE-tenderness. Ninety-six patients (48.5%) showed features of FDD: 70 DD and 26 IDP; 25 (12.6%) showed isolated structural outlet obstruction, and 23 (11.6%) showed isolated slow transit constipation. No predictors were found for IDP.

CONCLUSIONS: The subjective complaint of painful defecation added to the Rome III criteria is critical to improve the identification of specific subtypes of refractory chronic constipation, thus improving care and potentially decreasing the need for physiology testing.

PMID:40961385 | DOI:10.1111/nmo.70160

Acta Orthop. 2025 Sep 17;96:684-691. doi: 10.2340/17453674.2025.44595.

ABSTRACT

BACKGROUND AND PURPOSE: Traditional surgery for arthritis of the distal radioulnar joint (DRUJ), which typically involves resecting the ulnar head, is being increasingly challenged by newer techniques, such as prosthetic ulnar head replacement. The aim of our prospective cohort study was to investigate the clinical and patient-reported functional results, up to 2 years postoperatively, among patients with DRUJ arthritis treated with ulnar head replacement or resection.

METHODS: 40 patients were included and underwent either ulnar head replacement (n = 22) or ulnar head resections (n = 18), due to DRUJ pathology between 2015 and 2020. Patients were followed up at 3, 6, 12, and 24 months postoperatively by the means of Patient-Rated Wrist Evaluation (PRWE) (primary outcome), and Disability of the Arm, Shoulder and Hand (DASH) questionnaires, pain, range of forearm rotation, and grip strength (secondary outcomes). Postoperative complications were recorded. 19 and 16 patients, respectively, responded at the 24-months follow-up. Female sex and inflammatory arthritis were more common in the resection group. General linear regression analyses adjusting for diagnosis and baseline PRWE score were performed for our primary outcome.

RESULTS: The median and interquartile range (IQR) improvement in PRWE from baseline to 24 months was 69 (IQR 49-87) to 27 (IQR 6-48) in the replacement group and 60 (IQR 50-86) to 23 (IQR 5-44) in the resection group, indicating that both groups improved from baseline. There were no differences in unadjusted estimates at any time point. The adjusted means in PRWE at 24 months were 35 and 26 points in the replacement and resection groups, respectively, corresponding to a statistically insignificant mean difference of 8.6 (95% confidence interval -11.7 to 28.2). We found no statistically significant group differences in any of the secondary outcomes at any time point. Postoperative complications affected 6 patients with ulnar head replacement, whereas none were reported for patients with ulnar head resection.

CONCLUSION: We found that the outcome after ulnar head replacement is not superior to ulnar head resection in the short term.

PMID:40961374 | DOI:10.2340/17453674.2025.44595

JMIR Med Educ. 2025 Sep 17;11:e62666. doi: 10.2196/62666.

ABSTRACT

BACKGROUND: Applying functional anatomy to clinical examination techniques in shoulder examination is challenging for physicians at all learning stages. Anatomy teaching has shifted toward a more function-oriented approach and has increasingly incorporated e-learning. There is limited evidence on whether the integrated teaching of professionalism, clinical examination technique, and functional anatomy via e-learning is effective.

OBJECTIVE: This study aimed to investigate the impact of an integrated blended learning course on the ability of first-year medical students to perform a shoulder examination on healthy volunteers.

METHODS: Based on Kolb’s experiential learning theory, we designed a course on shoulder anatomy and clinical examination techniques that integrates preclinical and clinical content across all 4 stages of Kolb’s learning cycle. The study is a randomized, observer-blinded controlled trial involving first-year medical students who are assigned to one of two groups. Both groups participated in blended learning courses; however, the intervention group’s course combined clinical examination, anatomy, and professional behavior and included a peer-assisted practice session as well as a flipped classroom seminar. The control group’s course combined an online lecture with self-study and self-examination. After completing the course, participants uploaded a video of their shoulder examination. The videos were scored by 2 blinded raters using a standardized examination checklist with a total score of 40.

RESULTS: Thirty-eight medical students were included from the 80 participants needed based on the power calculation. Seventeen intervention and 14 control students completed the 3-week study. The intervention group students scored a mean of 34.71 (SD 1.99). The control students scored a mean of 29.43 (SD 5.13). The difference of means was 5.3 points and proved to be statistically significant (P<.001; 2-sided Mann-Whitney U test).

CONCLUSIONS: The study shows that anatomy, professional behavior, and clinical examination skills can also be taught in an integrated blended learning approach. For first-year medical students, this approach proved more effective than online lectures and self-study.

PMID:40961369 | DOI:10.2196/62666

JMIR Public Health Surveill. 2025 Sep 17;11:e71677. doi: 10.2196/71677.

ABSTRACT

BACKGROUND: Cervical cancer has been ranked as the fourth most common cancer affecting women, contributing to approximately 660,000 new diagnoses and 350,000 fatalities worldwide. Effective early screening has been shown to reduce cervical cancer incidence by up to 80% and prevent more than 40% of new cases.

OBJECTIVE: This study aims to assess a machine learning-based prediction model and identify the key predictors influencing cervical cancer screening uptake among women aged 30-49 years in sub-Saharan Africa.

METHODS: For this study, a weighted dataset of 33,952 individuals from the 2022 Demographic and Health Survey in Ghana, Kenya, Mozambique, and Tanzania was used. STATA version 17 (StataCorp) and Python 3.10 (Python Software Foundation) were used for data preprocessing and analysis. MinMax and standard scaler were applied for feature scaling, and recursive feature elimination was used for feature selection. An 80:20 ratio was applied for data splitting. Tomek links with random oversampling were used for handling class imbalance. A total of 7 models were selected and trained using both balanced and unbalanced datasets. Model evaluation was performed using area under the receiver operating characteristic curve, accuracy, and a confusion matrix.

RESULTS: The proportion of cervical cancer screening in sub-Saharan Africa was 13%, which is lower than reported in previous studies. Random forest was the best-performing model, achieving an accuracy of 78%, an area under the curve of 86%, an F1-score of 79%, a recall of 81%, and a precision of 77%. The waterfall plot’s Shapley Additive Explanations analysis showed that wealth status, awareness of sexually transmitted infections, HIV testing exposure, age at first sexual intercourse, educational level, residency, smartphone ownership, having a single sexual partner, and previous health status were predictors of cervical cancer screening.

CONCLUSIONS: Improving education and awareness, expanding access to screening (especially in rural areas), leveraging both digital health and community-based outreach, integrating screening with other health services, and addressing socioeconomic barriers are recommended strategies to increase cervical cancer screening rates in sub-Saharan Africa.

PMID:40961361 | DOI:10.2196/71677

Microb Genom. 2025 Sep;11(9). doi: 10.1099/mgen.0.001496.

ABSTRACT

Riboswitches are widely distributed RNA regulatory elements primarily found in prokaryotes. Over a decade ago, it was discovered that certain genes are regulated either by multiple tandemly arranged riboswitches or by riboswitches with tandem sensor domains.Riboswitches consist of a sensor domain, also known as an aptamer, and an expression platform, primarily regulating gene expression through transcription or translation attenuation, although other mechanisms such as RNA splicing or stability modulation are also possible. In tandemly arranged riboswitches, the first riboswitch is often positioned far from the ribosome binding site of the target gene, making transcriptional regulation a likely primary mechanism. In contrast, riboswitches with adjacent aptamers have a single expression platform, which may be located at varying distances from the regulated gene. Consequently, no inherent bias towards either transcriptional or translational regulation is expected in this case.Considering the reported enrichment of transcriptional riboswitches in certain phylogenetic clades, the present study analyses the distribution of tandemly arranged riboswitches and riboswitches with adjacent aptamers across various phylogenetic groups, as well as the tendencies of different riboswitch families to regulate genes in a contiguous fashion. Our results indicate that Bacillota is the phylum with the most notable families of tandemly arranged riboswitches. In contrast, regulation of gene expression via tandem sensor domains was predominantly associated with the Pseudomonadota phylum. On the other hand, our statistical analysis identified the T-box and cyclic dimeric guanosine monophosphate as the most prominent members of tandemly arranged riboswitches, while the glycine riboswitch is the most relevant family to be composed of adjacent aptamers.In addition, this article presents a comprehensive analysis of all relevant orthologous gene groups regulated by contiguous riboswitches, highlighting trends in cases where strict regulation is necessary due to the high metabolic cost of a pathway. Finally, we provide an in-depth discussion of the observed regulatory tendencies.

PMID:40961346 | DOI:10.1099/mgen.0.001496

Am Fam Physician. 2025 Sep;112(3):301-312.

ABSTRACT

Autism is a lifelong neurodevelopmental condition that affects approximately 1 in 31 US children and 1 in 45 US adults; autism spectrum disorder includes a wide range of neurologic diversity, symptoms, challenges, strengths, and abilities. The Diagnostic and Statistical Manual of Mental Disorders, 5th ed., text revision criteria for autism spectrum disorder require deficits in three areas of communication and social interaction across multiple settings, with at least two restricted or repetitive behaviors, not explained by another condition, and causing functional impairment. The American Academy of Pediatrics recommends screening for autism at ages 18 and 24 months in addition to routine developmental surveillance, whereas screening in adults is not recommended. Diagnosis should include a multidisciplinary team and a multidimensional assessment. Autistic individuals have a 20- to 30-year lower life expectancy than nonautistic people and experience higher rates of many chronic conditions, such as diabetes, epilepsy, gastrointestinal concerns, feeding disorders, and mental health disorders (eg, attention-deficit/hyperactivity disorder, depression, anxiety, schizophrenia). Treatment of children with autism spectrum disorder focuses on minimizing core deficits, maximizing functional independence, and preventing problem behaviors. Pharmacologic therapy may be indicated for related conditions or symptoms, such as sleep disorders, seizures, mental health conditions, behavior problems, and gastrointestinal issues. Melatonin effectively reduces sleep symptoms and improves daytime behaviors with minimal adverse effects. The SPACE (sensory, predictability, acceptance, communication, empathy) framework provides specific interventions that make health care more accessible and affirming to autistic patients.

PMID:40961308

Nutr Health. 2025 Sep 17:2601060251378785. doi: 10.1177/02601060251378785. Online ahead of print.

ABSTRACT

BackgroundLifestyle factors, including dietary fasting and structured eating habits, may influence neurodegenerative processes in Huntington’s disease (HD), yet little is known about dietary behaviors in this population.AimEvaluate the frequency of fasting habits, identify meal timing characteristics, and explore dietary composition choices in individuals with or at-risk for HD.MethodsAn electronic survey was distributed within the HD community. Responses were collected for one year and statistically analyzed.ResultsAmong 116 respondents, 42% reported practicing a fasting protocol, with 36% sustaining it for over a year and 40% applying it as a weight loss strategy. The most common type was daily 16:8 fasting. Mediterranean, low-carbohydrate, and vegetarian diets were the most frequently adopted structured dietary patterns.ConclusionsFasting and structured eating habits are common in the HD community, suggesting dietary interventions may be feasible and relevant. Future studies are needed to evaluate their safety and effects in HD.

PMID:40961265 | DOI:10.1177/02601060251378785