Nevin Manimala

Mol Oncol. 2025 Jul 25. doi: 10.1002/1878-0261.70100. Online ahead of print.

ABSTRACT

Spatial transcriptomics (ST) has emerged as a powerful tool to map gene expression patterns to the local tissue structure in cancer, enabling unprecedented insights into cellular heterogeneity and tumour microenvironments. As the technology matures, developing new, spatially informed analytical frameworks will be essential to fully leverage its potential to elucidate the complex organisation and emerging properties of cancer tissues. Here, we highlight key challenges in cancer spatial transcriptomics, focusing on three emerging topics: (a) defining cell states, (b) delineating cellular niches and (c) integrating spatial data with other modalities that can pave the way towards clinical translation. We discuss multiple analytical approaches that are currently implemented or could be adapted in the future in order to tackle these challenges, including classical biostatistics methods as well as methods inherited from geospatial analytics or artificial intelligence. In the rapidly expanding landscape of ST, such methodologies lay the foundation for biological discoveries that conceptualise cancer as an evolving system of interconnected niches.

PMID:40711978 | DOI:10.1002/1878-0261.70100

Clin Neuropsychol. 2025 Jul 25:1-21. doi: 10.1080/13854046.2025.2537902. Online ahead of print.

ABSTRACT

Background: Early differentiation between amnestic multidomain mild cognitive impairment (aMCI-md) and Alzheimer’s disease (AD) is critical for timely diagnosis and care planning. The Mattis Dementia Rating Scale-2 (DRS-2) is a multidomain cognitive screening tool with potential value in detecting early neurodegenerative changes, though its performance in distinguishing aMCI-md from early AD remains underexplored. Objective: To evaluate the diagnostic accuracy of the DRS-2 total and subscale scores in a Spanish clinical cohort by comparing cognitively unimpaired individuals, patients with aMCI-md, and those with early AD. Methods: We conducted a cross-sectional study including 684 participants: 333 cognitively healthy controls, 141 with aMCI-md, and 210 with early AD. The DRS-2 was administered as part of a neuropsychological battery. Receiver operating characteristic curves, area under the curve (AUC), and optimal cut-off values were used to assess discriminative performance. Results: The DRS-2 total score and the Memory and Initiation/Perseveration subscales demonstrated good discriminative accuracy across all diagnostic contrasts. In the most clinically relevant comparison (aMCI-md vs. early AD), both the total score and Memory subscale reached an AUC of .87, while Initiation/Perseveration followed closely (AUC = .83). The total score yielded 87.2% accuracy (cut-off = 126), and Memory alone achieved 86.6% accuracy (cut-off = 19). Attention and Construction subscales consistently showed limited diagnostic value. Conclusion: The DRS-2, particularly the Memory and Initiation/Perseveration subscales, appears to be a reliable tool for distinguishing the early stages of cognitive impairment, supporting its clinical use for early diagnosis and risk stratification in memory clinic settings.

PMID:40711805 | DOI:10.1080/13854046.2025.2537902

Gynecol Endocrinol. 2025 Dec;41(1):2532613. doi: 10.1080/09513590.2025.2532613. Epub 2025 Jul 25.

ABSTRACT

BACKGROUND: Abnormal uterine bleeding (AUB) impacts the quality of life of women globally. While international classifications and frameworks exist, there are still critical unmet needs in awareness, diagnosis, treatment, and patient support. To better understand these, the lived experiences of patients with AUB shared on social media can offer valuable insights.

OBJECTIVE: To identify and analyze unmet needs in the management of AUB as expressed during social media discussions.

METHODS: Using the social media listening tool Sprinklr Social (Sprinklr Inc.), public posts from X (X Corp.) related to AUB from seven countries (Brazil, China, India, Mexico, Pakistan, Saudi Arabia, Ukraine) over a 10-year period (2014-2024) were analyzed. Posts were categorized by topic, sentiment, and emotion; further analyses assessed patients’ unmet needs and feelings.

RESULTS: A total of 926 posts were included. Analysis revealed five critical unmet needs: lack of awareness and understanding (41.8%), impact on wellbeing (27.6%), diagnosis issues (10.9%), dissatisfaction with treatment options (9.7%), and undervalued impact and advocacy (8.6%). Posts about diagnosis and symptoms carried the most negative sentiments; many patients expressed frustration over delayed diagnoses and dissatisfaction with treatment options. Additionally, the emotional and psychological burden of AUB was a recurring theme, suggesting the need for more holistic care approaches.

CONCLUSIONS: Gaps in AUB management were identified, with strong emphasis on the need for better patient education, more effective diagnostic processes, and personalized treatment strategies. Incorporating patient voices during the development of treatment guidelines and healthcare policies is crucial for addressing these unmet needs and improving patient outcomes.

PMID:40711799 | DOI:10.1080/09513590.2025.2532613

JAMA Netw Open. 2025 Jul 1;8(7):e2524181. doi: 10.1001/jamanetworkopen.2025.24181.

NO ABSTRACT

PMID:40711795 | DOI:10.1001/jamanetworkopen.2025.24181

JAMA Netw Open. 2025 Jul 1;8(7):e2523220. doi: 10.1001/jamanetworkopen.2025.23220.

ABSTRACT

IMPORTANCE: Adherence to quality-of-care indictors (QCIs) is associated with better Staphylococcus aureus bacteremia (SAB) outcomes. It is unknown whether clinical trial participation adventitiously improves QCI adherence and clinical outcomes compared with nontrial routine care for SAB.

OBJECTIVE: To evaluate whether health care practitioners of trial participants with methicillin-resistant Staphylococcus aureus (MRSA) bacteremia have better QCI adherence compared with practitioners of contemporaneous nontrial patients with MRSA bacteremia and whether QCI adherence or trial participation is associated with lower mortality.

DESIGN, SETTING, AND PARTICIPANTS: This ad hoc, post hoc analysis of the Combination Antibiotics for Methicillin-Resistant Staphylococcus aureus (CAMERA2) Trial included 17 CAMERA2 hospital sites from 4 countries. The present study involved data collection mirroring the CAMERA2 case report forms from nontrial patients selected from sites’ CAMERA2 screening logs. The newly collected data were analyzed with existing data from trial participants. Both groups of patients were diagnosed with MRSA bacteremia between August 2015 and July 2018. Statistical analyses were performed from September 2024 to February 2025.

EXPOSURES: Nontrial vs trial participation, including health care practitioner adherence to 7 evidence-based QCIs (individually and collectively) for SAB management.

MAIN OUTCOME AND MEASURES: All-cause 90-day mortality; the association of the exposures with this outcome was assessed using Cox proportional hazards regressions. Multiple sensitivity analyses were performed, including propensity score matching and exclusion of early deaths.

RESULTS: This study included 722 participants (467 nontrial [64.7%] and 255 trial [35.3%]; mean [SD] age, 63.2 [18.4] years; 482 [66.8%] male). Demographics were comparable in the 2 study groups. Nontrial patients had a higher range of Charlson Comorbidity Index (median, 2.0 [range, 0-16.0] vs 2.0 [range, 0-13.0]; P < .001) and Pitt bacteremia score (median, 1.0 [range, 1.0-12.0] vs 1.0 [range, 1.0-7.0]; P < .001) compared with trial participants. Ninety-day mortality was not significantly different in the nontrial and trial groups (106 of 457 [23.2%] vs 48 of 251 [19.1%]; P = .25). Health care practitioners of nontrial patients had a lower mean (SD) number of adherent QCIs compared with practitioners of trial participants (3.90 [1.38] vs 4.28 [1.17]; P = .003). While increasing number of adherent QCIs was associated with lower 90-day mortality (adjusted hazard ratio [AHR], 0.73; 95% CI, 0.59-0.91; P = .005), adherence to QCIs individually was not associated with lower mortality. Study group (nontrial vs trial) was not associated with mortality (AHR, 1.08; 95% CI, 0.73-1.61; P = .68).

CONCLUSIONS AND RELEVANCE: In this post hoc analysis of a randomized clinical trial, health care practitioners of trial participants had greater adherence to QCIs for MRSA bacteremia management compared with practitioners of nontrial patients. Trial participation was not associated with lower mortality.

PMID:40711789 | DOI:10.1001/jamanetworkopen.2025.23220

JAMA Netw Open. 2025 Jul 1;8(7):e2523434. doi: 10.1001/jamanetworkopen.2025.23434.

ABSTRACT

IMPORTANCE: Death after cytoreductive surgery for advanced-stage ovarian cancer is more frequent in low-volume hospitals. Neoadjuvant chemotherapy (NACT) has been shown to reduce surgical complexity, complications, and surgical mortality without compromising oncologic outcomes.

OBJECTIVE: To measure whether more frequent NACT utilization is associated with postoperative mortality and overall survival after cytoreductive surgery, especially in low-volume hospitals.

DESIGN, SETTING, AND PARTICIPANTS: This cross-sectional study included patients treated for newly diagnosed stage III or IV epithelial ovarian cancer at Commission on Cancer-accredited cancer programs in the United States between January 2010 and December 2019. Data were analyzed from August 2023 to April 2025.

EXPOSURES: The main exposures of interest were cancer program-level rates of NACT and tertile of program mean annual volume of cytoreductive surgery (<12.0, 12.0-23.9, or ≥24.0 cases/y).

MAIN OUTCOMES AND MEASURES: Standardized rates and odds ratios (ORs) for 90-day perioperative morality and differences in 60-month life expectancy (restricted mean survival time).

RESULTS: A total of 70 707 patients (mean [SD] age, 63.1 [12.1] years; 5807 [8.2%] Black, 4745 [6.7%] Hispanic, and 56 336 [79.7%] White) treated in 1333 programs were identified. After adjusting for observed demographic and clinical covariates, 90-day surgical mortality was lower in centers with higher NACT rates, and the magnitude of this association differed by hospital volume (P for interaction < .001). High utilization of NACT (59%) compared with low utilization (22%) was associated with a larger decrease in 90-day mortality in high-volume centers (OR, 0.26; 95% CI, 0.17-0.41; rates, 10.0% vs 2.9%) compared with average-volume centers (OR, 0.49; 95% CI, 0.33-0.72; rates, 7.3% vs 3.7%) or low-volume centers (OR, 0.48; 95% CI, 0.39-0.60; rates, 9.5% vs 4.8%). Among high-volume centers, high utilization was associated with a 4.0 month (95% CI, 1.6-6.5 month)-improvement in 60-month life expectancy compared with low NACT utilization (42.2 vs 38.1 months).

CONCLUSIONS AND RELEVANCE: In this cross-sectional study, treatment in high-volume centers with high NACT utilization was associated with the lowest 90-day surgical mortality and longest 60-month survival for patients with advanced stage ovarian cancer.

PMID:40711787 | DOI:10.1001/jamanetworkopen.2025.23434

JAMA Health Forum. 2025 Jul 3;6(7):e251930. doi: 10.1001/jamahealthforum.2025.1930.

ABSTRACT

IMPORTANCE: Independent evaluations of Bundled Payments for Care Improvement Advanced (BPCI-A) have focused on hospitals and have not assessed the performance of physicians in participating physician group practices (PGPs). However, PGPs are accountable for a larger proportion of surgical procedures, including for lower-extremity joint replacement, in the BPCI-A model than are hospitals.

OBJECTIVE: To evaluate the association of treatment by BPCI-A-participating physicians and hospitals with health care spending, quality, and utilization for joint replacement procedures compared to nonparticipants.

DESIGN, SETTING, AND PARTICIPANTS: This cohort study used Medicare claims of beneficiaries receiving lower-extremity joint replacement between April 2016 and September 2019 and data on BPCI-A-participating PGPs and hospitals to assess spending, quality, and utilization. Differences-in-differences methods adjusting for patient and market characteristics (aDID) were used with matched comparison groups of nonparticipating physicians and hospitals. Data analysis was performed from January 2023 to January 2025.

EXPOSURES: Lower-extremity joint replacement by a physician in a PGP or hospital that began BPCI-A participation in October 2018.

MAIN OUTCOMES AND MEASURES: Ninety-day total episode spending for joint replacement. Secondary outcomes were postacute care utilization, mortality, hospital readmissions, and joint replacement complications.

RESULTS: The matched cohort included 846 529 Medicare beneficiaries (mean [SD] age, 73.7 [8.3] years; 63.8% female) who obtained a joint replacement in April 2016 to September 2019, of whom 281 189 were treated by 2820 physicians in BPCI-A-participating PGPs, and 69 107 by 174 BPCI-A-participating hospitals. An additional 28 309 beneficiaries were treated by physicians and hospitals both participating in BPCI-A. The remaining 467 924 were treated by 4671 nonparticipating physicians and 432 nonparticipating hospitals. Before BPCI-A participation, total unadjusted baseline episode spending was $26 483 for participating physicians and $29 854 for participating hospitals. Treatments by BPCI-A participating physicians and hospitals were each associated with differentially lower total spending (physician aDID, -$855; 95% CI, -$1074 to -$636; hospital aDID, -$613; 95% CI, -$1039 to -$187). Treatment by a BPCI-A-participating physician or hospital was associated with differentially lower institutional postacute care utilization. Physician participation was associated with a differential increase in outpatient visits 7 days postdischarge (aDID, 2.9 percentage points; 95% CI, 2.0 to 3.8), while hospital participation was not associated with a change in outpatient visits. Differential changes in mortality, readmissions, and complications were not observed for either participant type.

CONCLUSIONS AND RELEVANCE: This cohort study found that participation in BPCI-A for joint replacement was associated with differentially lower total spending for both physicians and hospitals. Given that physicians in PGPs accounted for 73% of all the joint replacement episodes, these findings highlight the importance of facilitating alignment between hospitals and physicians in future bundled-payment models, including those that allow only hospitals.

PMID:40711779 | DOI:10.1001/jamahealthforum.2025.1930

JAMA Health Forum. 2025 Jul 3;6(7):e252223. doi: 10.1001/jamahealthforum.2025.2223.

ABSTRACT

IMPORTANCE: Estimating global lives and life-years saved is important to put into perspective the benefits of COVID-19 vaccination. Prior studies have focused mainly on the pre-Omicron period or only on specific regions, and lack crucial life-year calculations and often depend on strong modeling assumptions with unaccounted uncertainty.

OBJECTIVE: To calculate the lives and life-years saved by COVID-19 vaccination worldwide from the onset of the vaccination campaigns and until October 1, 2024.

DESIGN, SETTING, AND PARTICIPANTS: This comparative effectiveness study considered different strata of the worldwide population according to age, community-dwelling and long-term care residence status, pre-Omicron and Omicron periods, and vaccination before and after a SARS-CoV-2 infection.

EXPOSURES: Any COVID-19 vaccination in any schedule and number of doses.

MAIN OUTCOME MEASURE: Death.

RESULTS: In the main analysis, more than 2.5 million deaths were averted (1 death averted per 5400 vaccine doses administered). Eighty-two percent were among people vaccinated before any infection, 57% were during the Omicron period, and 90% pertained to people 60 years or older. Sensitivity analyses suggested 1.4 to 4.0 million lives were saved. Some sensitivity analyses showed a preponderance of the benefit during the pre-Omicron period. An estimated 14.8 million life-years were saved (1 life-year saved per 900 vaccine doses administered). The sensitivity range was 7.4 to 23.6 million life-years. Most life-years saved (76%) were among people 60 years or older, but long-term care residents contributed only 2% of the total. Children and adolescents (0.01% of lives saved and 0.1% of life-years saved) and young adults aged 20 through 29 years (0.07% of lives saved and 0.3% of life-years saved) had very small contributions to the total benefit.

CONCLUSIONS AND RELEVANCE: Estimates in this study are substantially more conservative than previous calculations focusing mostly on the first year of vaccination, but they still clearly demonstrate a major overall benefit from COVID-19 vaccination during the years 2020-2024. Most benefits in lives and life-years saved was secured for a portion of older persons, a minority of the global population.

PMID:40711778 | DOI:10.1001/jamahealthforum.2025.2223

DNA Cell Biol. 2025 Jul 21. doi: 10.1177/10445498251361047. Online ahead of print.

ABSTRACT

Tail fat weight is a key economic trait in fat-tailed sheep; reducing tail fat deposition is of significant importance for improving the economic efficiency of sheep farming. In this article, we measured the live weight before slaughter, tail fat weight, and carcass weight of Hu male sheep at 6 months of age and performed the descriptive statistical analysis. The results indicated the coefficient of variation of tail fat-related-traits ranged from 25% to 50%. Simultaneously, we selected IGFBP3 and TUSC5 as candidate genes based on their close association with fat deposition. Target regions were amplified using gene-specific primers in PCR, followed by Sanger sequencing of PCR products to identify genetic variants. Polymorphisms were subsequently validated using the KASPar genotyping assay. Finally, quantitative reverse transcription PCR (qRT-PCR) was performed to determine the expression levels of IGFBP3 and TUSC5. Our findings revealed a missense mutation (g.83695349 C>T) in exon 1 of the IGFBP3 gene and a synonymous mutation (g.41771645 C>T) in exon 2 of the TUSC5 gene. Association analysis showed that these mutations were significantly correlated (p < 0.05) with tail fat weight traits. Moreover, the tail fat weight of the mutant genotypes (CT and TT) was significantly reduced compared with that of the CC genotype, suggesting that the gene may exert a negative regulatory effect on this trait, thereby leading to the reduction of tail fat weight. Furthermore, the genotype combinations showed a significant relationship with tail fat traits. Moreover, qRT-PCR results showed that TUSC5 and IGFBP3 genes were expressed in all experimental tissues of Hu sheep, and the highest expression was observed in tail fat compared with other tissues (heart, liver, spleen, lung, kidney, rumen, duodenum, muscle, and lymph). Notably, their expression levels were significantly lower in the large-tail fat group than in the small-tail fat group. Overall, these results will provide novel candidate variation for reducing tail fat deposition in sheep breeding practice.

PMID:40711772 | DOI:10.1177/10445498251361047

Pharm Stat. 2025 Sep-Oct;24(5):e70027. doi: 10.1002/pst.70027.

ABSTRACT

A major emphasis in personalized medicine is to optimally treat subgroups of patients who may benefit from certain therapeutic agents. One relevant study design is the targeted design, in which patients have consented for their specimens to be obtained at baseline and the specimens are sent to a laboratory for assessing the biomarker status prior to randomization. Here, only biomarker-positive patients will be randomized to either an experimental or the standard of care arms. Many biomarkers, however, are derived from patient tissue specimens, which are heterogeneous leading to variability in the biomarker levels and status. This heterogeneity would have an adverse impact on the power of an enriched biomarker clinical trial. In this article, we show the adverse effect of using the uncorrected sample size and overcome this challenge by presenting an approach to adjust for misclassification for the targeted design. Specifically, we propose a sample size formula that adjusts for misclassification and apply it in the design of two phase III clinical trials in renal and prostate cancer.

PMID:40711765 | DOI:10.1002/pst.70027