Tag: nevin manimala

JCO Precis Oncol. 2025 Oct;9:e2500076. doi: 10.1200/PO-25-00076. Epub 2025 Dec 18.

ABSTRACT

PURPOSE: To investigate tumor mutation variations across different racial/ethnic groups to better understand implications for targeted cancer therapies.

METHODS: A retrospective analysis of 5,045 patients at University of New Mexico Comprehensive Cancer Center who underwent tumor genetic testing between January 2015 and April 2022 was conducted. Data were standardized from internal genetic tests, FoundationOne, and Guardant next-generation sequencing panels. Chi-square tests, one-way analysis of variance, and negative binomial regression estimated differences in mutation rates across race/ethnicity, adjusting for cancer type, age, testing year, and number of genes screened. Primary outcomes included tumor mutation rates and their variation across racial/ethnic groups. Specific focus was placed on mutation frequencies in common genes, and association between race/ethnicity and mutations detected, adjusted for covariates.

RESULTS: Among 5,045 patients-Hispanic/Latino (30%), American Indian (5.7%), Asian/Hawaiian Native (1.9%), Black (1.5%), non-Hispanic White (41%), and other/unknown (19.7%)-mutations were identified most commonly for Asian/Hawaiian Native individuals, with a rate of 0.068 mutations per gene screened (95% CI, 0.051 to 0.090), followed by White individuals (rate = 0.061, 95% CI, 0.051 to 0.072). Fewest mutations were identified for Black individuals, with a rate of 0.045 mutations per gene screened (95% CI, 0.033 to 0.061). Single-gene comparisons suggested BRAF mutations to be most prevalent in non-Hispanic Whites (5.8%, P = .015) while EGFR mutations were most common in Asian/Hawaiian Native patients (10.53%, P = .005).

CONCLUSION: This study highlights substantial heterogeneity in tumor mutations across racial/ethnic groups while emphasizing the need for wider understanding of genomics and tailored approaches in cancer treatment. Findings underscore the need for equitable genomic testing, tailored therapies, and inclusive cancer care. Further research is necessary to bridge existing disparities, ensuring comprehensive, personalized cancer treatment for all patients.

PMID:41411616 | DOI:10.1200/PO-25-00076

JCO Precis Oncol. 2025 Oct;9:e2500638. doi: 10.1200/PO-25-00638. Epub 2025 Dec 18.

ABSTRACT

PURPOSE: Metabolic dysfunction-associated steatotic liver disease (MASLD) is a major cause of hepatocellular carcinoma (HCC), yet current screening strategies overlook the genetic complexity of MASLD. We hypothesized that capturing this complexity through a multitrait polygenic approach could improve HCC prevention.

METHODS: Using genome-wide association data for 10 MASLD-related traits in individuals of European ancestry, we constructed a meta-polygenic risk score (metaPRS) in the UK Biobank. We evaluated its performance in HCC prediction and its utility in stratified screening. Risk advancement period (RAP) analysis estimated how much earlier individuals in different genetic risk groups reach comparable risk levels.

RESULTS: The metaPRS that incorporated genome-wide variants achieved a C-statistic of 0.686 for HCC prediction, outperforming existing PRSs. Individuals in the top 20% of genetic risk had a 5.33-fold higher HCC risk than those in the bottom 20%. RAP analysis showed that high-risk individuals reached the HCC risk threshold 11.91 years earlier than the intermediate group, whereas low-risk individuals reached it 5.49 years later, suggesting a shift in recommended screening age from 65 to 43 years. Genetic stratification by the metaPRS also improved the predictive performance of noninvasive fibrosis scores (eg, Forns score). Combining high genetic risk with an elevated Forns score yielded a 10-year HCC risk of 2.68%, compared with 0.01% in the lowest-risk group-reducing the number needed to screen from 7,918 to 27.

CONCLUSION: The MASLD-related metaPRS supports effective population risk stratification and enables a layered HCC screening strategy combining genetic risk profiling with targeted clinical assessment.

PMID:41411614 | DOI:10.1200/PO-25-00638

JCO Precis Oncol. 2025 Oct;9:e2500235. doi: 10.1200/PO-25-00235. Epub 2025 Dec 18.

ABSTRACT

PURPOSE: About 60% of patients with high-risk neuroblastoma relapse. Specific mRNA detection in bone marrow (BM) by reverse transcriptase quantitative PCR (RT-qPCR) is associated with survival outcomes. Peripheral blood (PB) sampling is less invasive. Therefore, we prospectively validated an RT-qPCR panel of neuroblastoma mRNA in PB of patients with high-risk neuroblastoma, treated in NB2004-HR (GPOH) and NBL2009 (DCOG).

METHODS: From 312 patients, 634 PB samples were prospectively collected (2009-2017) at diagnosis, after two cycles and end-of-induction therapy. RT-qPCR was performed using our panel of neuroblastoma mRNA markers: PHOX2B, TH, DDC, CHRNA3, and DBH. Results were compared with paired BM samples. The association between neuroblastoma detection and event-free survival (EFS) and overall survival (OS) was estimated using Kaplan-Meier’s methodology and multivariable Cox regression model.

RESULTS: Clear correlation between calculated infiltration by neuroblastoma mRNA expression in PB and BM was seen at diagnosis (r_s 0.70 [95% CI, 0.62 to 0.76]), and heterogeneity was seen after two cycles (0.37 [95% CI, 0.12 to 0.58]) and end of induction (0.61 [95% CI, 0.10 to 0.87]). mRNA expression was significantly lower in PB compared with BM. At diagnosis, PB infiltration ≥1% was a prognostic factor for survival: adjusted hazard ratio (HR) was 2.37 [95% CI, 1.56 to 3.60] for EFS and 2.60 [1.65-4.08] for OS. At the end of induction, PHOX2B positivity in PB samples (n = 11) was associated with poor outcomes: HR 3.06 [1.51-6.20] for EFS and 2.88 [1.36-6.11] for OS. In patients with ≥10% BM infiltration at diagnosis, detection of the mRNA panel in PB samples could significantly distinguish between survival groups; the adjusted HR of PB infiltration ≥1% was 2.09 [1.01-4.30] for OS.

CONCLUSION: PB infiltration is associated with EFS and OS at diagnosis; it is also significantly associated with survival outcomes of patients with ≥10% BM infiltration at diagnosis. During follow-up, neuroblastoma mRNA detection in PB can be of added value, when BM analysis is not possible.

PMID:41411610 | DOI:10.1200/PO-25-00235

Neurology. 2026 Jan 27;106(2):e214488. doi: 10.1212/WNL.0000000000214488. Epub 2025 Dec 18.

ABSTRACT

OBJECTIVES: Stroke disproportionately affects Black individuals in the United States. We aimed to assess differences between Black and White individuals in the associations between health-related behaviors, measured with the Brain Care Score (BCS; a tool encompassing 12 modifiable risk factors), and incident stroke.

METHODS: We analyzed data from REGARDS, a prospective US cohort of Black and White adults aged 45 years or older. Participants who were stroke free at baseline with complete BCS data were included. We assessed the BCS (range: 0-21; higher indicating healthier behaviors) and its associations with incident stroke in Black vs White individuals. Cox proportional hazard models were stratified by race (Black vs White) and adjusted for demographics and socioeconomic factors. Effect sizes were compared using Z-statistics.

RESULTS: Among 10,861 participants (30.6% Black, 57.4% female, mean age: 63.2 years), 696 strokes occurred over a median of 15.9 years. A five-point higher BCS was associated with lower stroke risk in both groups, with larger magnitude among Black vs White individuals (HR: 0.47 [95% CI 0.36-0.61] vs 0.75 [95% CI 0.62-0.92]; Z-statistic p value = 0.0045).

DISCUSSION: The BCS is associated with incident stroke in a biracial US cohort and shows larger effect sizes within Black compared with White individuals, suggesting that BCS improvement may yield greater stroke prevention benefits for Black populations.

PMID:41411605 | DOI:10.1212/WNL.0000000000214488

J Opt Soc Am A Opt Image Sci Vis. 2025 Dec 1;42(12):1929-1935. doi: 10.1364/JOSAA.574392.

ABSTRACT

Partially coherent vortex beams have attracted growing interest due to their enhanced robustness and unique propagation characteristics in complex media. In this work, we experimentally investigate the behavior of partially coherent fractional vortex beams as they propagate through atmospheric turbulence. The beams are generated using a phase-only spatial light modulator and a rotating ground-glass disk modeled by the Gaussian Schell framework, and their degree of partial coherence is quantitatively characterized using a Young’s double-slit interference plate. After transmission through a 1.2 m turbulence simulator, the effective beam radius exhibits a smoothed, quasi-linear growth trend between successive integer topological charges, indicating the suppression of discrete modal transitions by the combined effects of partial coherence and turbulence. The scintillation index decreases overall with increasing topological charge, while local enhancements near half-integer orders reveal the heightened turbulence sensitivity of modal interference. Moreover, partially obstructed PCFVBs show partial statistical self-reconstruction after turbulent propagation, whereas a fully coherent control under identical conditions shows no appreciable recovery, ruling out a purely diffractive fill-in. These results provide the first, to our knowledge, comprehensive experimental insight into the interplay among coherence, turbulence, and fractional vortex structure, offering new perspectives for designing turbulence-resistant structured-light systems.

PMID:41411568 | DOI:10.1364/JOSAA.574392

J Opt Soc Am A Opt Image Sci Vis. 2025 Dec 1;42(12):1890-1899. doi: 10.1364/JOSAA.565216.

ABSTRACT

The influence of disorder in the spatial arrangement of identical, homogeneous spherical particles of an infinite two-dimensional (2D) array on the energy density spectra of the electric and magnetic fields on their surfaces under normal incidence of a plane electromagnetic wave is studied. The consideration is based on a semi-analytical statistical method (SASM) developed by us. Radial distribution functions based on the hard-disk model are used to simulate particle arrangements in arrays. We wrote a formula for this function describing the perfect azimuthally averaged lattice and analyzed in detail the energy densities for different deviations of particle centers from the nodes of the perfect lattice. The calculation results for a partially ordered array and imperfect and perfect lattices of silver (Ag), crystalline silicon (c-Si), and titanium oxide (TiO₂) particles with sizes of 50 and 300 nm are presented in the wavelength range of 0.3-1.1 µm for a host medium with a refractive index close to that of water. They demonstrate the contribution of the disorder effect to the optical response of the system and allow finding the optimal characteristics of lattice-induced resonances for energy densities on the particle surface. Such data are necessary for solving problems of increasing the efficiency of converting light energy absorbed by the system into other types of energy. The spectra of energy densities obtained under the SASM are in excellent agreement with the data of the numerical finite element method (FEM). To complete the picture, the near-field data are accompanied by far-field data for the incoherent component of the light.

PMID:41411564 | DOI:10.1364/JOSAA.565216

J Opt Soc Am A Opt Image Sci Vis. 2025 Dec 1;42(12):1846-1863. doi: 10.1364/JOSAA.576308.

ABSTRACT

We introduce two families of vergence functions to express ocular wavefront aberrations in diopters, bridging aberrometry, and clinical refraction. First, we build a fully orthogonal vergence basis (V~), analogous to Zernike polynomials, which preserves mode orthogonality and supports unbiased coefficient statistics. In our VL-VH basis (V), a clear separation between low-degree and high-degree prevents the intrusion of low-degree terms into high-degree modes, which could otherwise hinder direct clinical interpretation. The vergence function expansions in both bases are derived from wavefront slopes through radial differentiation. We demonstrate their clinical utility through three cases: a normal eye, a keratoconic eye, and a post-myopic LASIK eye. The VL-VH basis provides stable refraction estimates across pupil sizes by fitting low-degree terms over central regions, closely matching subjective refraction. In contrast, the orthogonal V~ basis shows pupil-dependent refraction due to peripheral wavefront influence. In eyes with significant spherical aberration, the bases yield markedly different refractive predictions, with VL-VH better aligning with clinical measurements. Pyramid plots, dioptric maps, and coefficient histograms facilitate aberration visualization and diagnosis. These vergence-based tools enhance the integration of advanced aberrometry into clinical practice.

PMID:41411558 | DOI:10.1364/JOSAA.576308

J Clin Gastroenterol. 2025 Dec 19. doi: 10.1097/MCG.0000000000002309. Online ahead of print.

ABSTRACT

GOALS: To compare the effectiveness, durability, and safety of vedolizumab and upadacitinib for CD through 52 weeks.

BACKGROUND: Comparative real-world data for vedolizumab versus upadacitinib in Crohn’s disease (CD) are limited.

STUDY: This retrospective cohort study included 139 adults with active CD who began vedolizumab (n=72) or upadacitinib (n=67) during 2023 at a large academic health system. Co-primary outcomes were steroid-free clinical remission (SFCR) at 12 and 52 weeks and treatment discontinuation within 52 weeks; secondary outcomes included clinical response at 12 and 52 weeks. Inverse probability of treatment weighting balanced relevant confounders. Logistic regression was used for binary outcomes and Cox proportional hazards and competing risks regression were used for treatment discontinuation. Adverse events were ascertained by manual chart review.

RESULTS: After weighting, all covariates were balanced (standardized mean differences <0.10). At 12 weeks, vedolizumab was associated with lower odds of clinical response versus upadacitinib (OR: 0.36; 95% CI: 0.16-0.85). There were no significant differences for SFCR, treatment discontinuation, or other outcomes through 52 weeks. Competing risks regression, accounting for adverse events as competing events, showed a higher incidence of treatment discontinuation due to nonresponse for vedolizumab, but this did not reach statistical significance. Adverse events within 52 weeks were comparable (vedolizumab 33% vs. upadacitinib 39%; P=0.45), and discontinuations due to adverse events were infrequent (3% vs. 6%).

CONCLUSIONS: In this tertiary-center cohort, upadacitinib produced faster clinical response at 12 weeks, but SFCR, durability, and safety profiles were similar through 52 weeks.

PMID:41411531 | DOI:10.1097/MCG.0000000000002309

J Glob Health. 2025 Dec 19;15:04323. doi: 10.7189/jogh.15.04323.

ABSTRACT

BACKGROUND: Risk prediction models for cardiovascular diseases (CVDs) have been widely applied in clinical practice and in designing prevention policies globally, yet their accuracy across different regions with distinct epidemiological profiles remains uncertain. We examined the regional variation in risk distribution and agreement between these models.

METHODS: We analysed 53 nationally representative health surveys in seven regions. Using the World Health Organization (WHO), SCORE2, and Framingham CVD risk prediction models, we estimated the respondents’ 10-year CVD risk and categorised them into low-, moderate-, or high-risk groups.

RESULTS: We included 86 430 individuals aged 40-69 years without a history of CVD in our analysis. Globally, CVD risk estimates differed substantially across models (WHO: 7.75%; 95% confidence interval (CI) = 7.70-7.80; SCORE2: 3.72%; 95% CI = 3.69-3.75; Framingham: 12.42%; 95% CI = 12.34-12.50). We also noted regional disparities in identifying moderate- and high-risk subjects, particularly in South Asia (WHO: 12.57%; 95% CI = 11.63-13.51; SCORE2: 18.24%; 95% CI = 17.14-19.33; Framingham: 29.40%; 95% CI = 28.11-30.70), sub-Saharan Africa (WHO: 16.30%; 95% CI = 15.78-16.83; SCORE2: 22.69%; 95% CI = 22.09-23.28; Framingham: 33.85%; 95% CI = 33.18-34.52), East Asia & the Pacific (WHO: 21.06%; 95% CI = 20.57, 21.55; SCORE2: 31.03%; 95% CI = 30.47, 31.59; Framingham: 45.54%; 95% CI = 44.93-46.14), and Latin America & the Caribbean (WHO: 23.09%; 95% CI = 21.48-24.70; SCORE2: 41.56%; 95% CI = 39.68-43.44; Framingham: 55.83%; 95% CI = 53.94-57.72), with greater than two-fold differences across models. Agreement in classifying individuals into low-, moderate-, or high-risk groups remained relatively high across risk models (63.1%), but varied considerably across regions, from 73.91% in South Asia to 47.54% in Latin America & the Caribbean.

CONCLUSIONS: The CVD risk estimates produced by the WHO, SCORE2, and Framingham models varied significantly across regions, with poor consistency in identifying at-risk individuals in some regions. These discrepancies may lead to undertreatment and inefficient use of otherwise limited healthcare resources. Region-specific adaptations are needed to enhance risk targeting, promote equity, and improve the overall effectiveness of primary prevention.

PMID:41411530 | DOI:10.7189/jogh.15.04323

J Am Acad Orthop Surg Glob Res Rev. 2025 Dec 16;9(12). doi: 10.5435/JAAOSGlobal-D-25-00397. eCollection 2025 Dec 1.

ABSTRACT

BACKGROUND: Limited data exist on factors contributing to delayed repair of patellar tendon ruptures. This study describes the experience of a single surgeon managing acute and chronic patellar tendon tears, focusing on patient demographics, socioeconomic characteristics, and short-term surgical outcomes.

METHODS: We conducted a retrospective cohort analysis of patellar tendon repairs performed at a single institution from January 2017 to January 2024. Patients were stratified into acute or chronic groups based on whether surgery occurred within 6 weeks of injury. Socioeconomic background was assessed using the area deprivation index, reported as national percentiles (1% to 100%) and state-normed deciles (1 to 10), with higher rankings indicating greater disadvantage. Mann-Whitney U and chi square tests were used for analysis.

RESULTS: Of the 70 patients included, 45 underwent acute and 25 chronic repairs. Groups did not differ significantly in age, body mass index, race/ethnicity, comorbidities, insurance status, or area deprivation index scores. Surgical complications, infection, revision surgery rates, and postoperative range of motion scores were not statistically different. Functional outcomes such as strength and return to work were not measured.

DISCUSSION: Within our predominantly minority, single-surgeon cohort, our analysis of socioeconomic characteristics revealed an average to moderate level of disadvantage with no notable demographic differences between the two groups. In addition, when appropriately managed, we found no statistically significant differences in surgical complications and postoperative range of motion values. These results reflect a specific practice setting and population. Broader studies incorporating functional outcomes and more diverse populations are needed to better understand delayed presentations and optimize care.

PMID:41411521 | DOI:10.5435/JAAOSGlobal-D-25-00397