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Background Exosomes, extracellular vesicles pivotal in cancer intercellular communication, encapsulate biomolecules with potential as diagnostic and prognostic biomarkers. Efficient isolation is essential for accurate molecular profiling. This study compares three exosome isolation methods—size exclusion chromatography (SEC), lectin-binding, and TIM4-binding—for proteomic and miRNA analysis of plasma exosomes in cancer. Methods Plasma exosomes from patients with non-small cell lung cancer (NSCLC, N = 22), castration-resistant prostate cancer (CRPC, N = 7), and healthy controls (N = 15) were analyzed. Liquid chromatography-tandem mass spectrometry profiled exosomal proteins, and small RNA sequencing identified miRNAs. Results SEC, lectin-binding, and TIM4-binding methods identified 122, 153, and 87 proteins, and 335, 89, and 181 miRNAs, respectively. SEC detected the most unique miRNAs (183), while lectin-binding excelled in unique protein detection (56). In CRPC, 69 proteins and 21 miRNAs differed significantly ( p  < 0.05) from controls, with SEC identifying 11 proteins and 6 miRNAs, lectin-binding detecting 40 proteins and 1 miRNA, and TIM4-binding revealing 18 proteins and 14 miRNAs. In NSCLC, 33 proteins and 15 miRNAs showed differential expression ( p  < 0.05), with SEC detecting 14 proteins and 3 miRNAs, lectin-binding identifying 2 proteins, and TIM4-binding uncovering 17 proteins and 12 miRNAs. Conclusions The choice of exosome isolation method profoundly influences molecular profiling, with SEC optimizing miRNA detection, lectin-binding enhancing protein capture, and TIM4-binding enriching cancer-specific miRNAs. These findings underscore the need for tailored isolation strategies to unlock exosomes’ potential as precise, multi-omic biomarkers for cancer diagnosis and monitoring.

Background Quantitative computed tomography (CT) assessment of visceral adiposity may be superior to body mass index (BMI) as a predictor of surgical morbidity. We sought to examine the association of CT measures of obesity and BMI with short-term postoperative outcomes in colon cancer patients. Methods In this retrospective study, 110 patients treated with colectomy for stage I–III colon cancer were classified as obese or non-obese by preoperative CT-based measures of adiposity or BMI [obese: BMI ≥ 30 kg/m 2 , visceral fat area (VFA) to subcutaneous fat area ratio ( V / S ) ≥0.4, and VFA > 100 cm 2 ]. Postoperative morbidity and mortality rates were compared. Results Obese patients, by V / S and VFA but not BMI, were more likely to be male and have preexisting hypertension and diabetes. The overall complication rate was 25.5%, and there were no mortalities. Obese patients by VFA (with a trend for V / S but not BMI) were more likely to develop postoperative complications as compared to patients classified as non-obese: VFA (30.5 vs.10.7%, p =  0.03), V / S (29.2 vs. 9.5%, p  = 0.05), and BMI (32.4 vs. 21.9%, p  = 0.23). Conclusions Elevated visceral obesity quantified by CT is associated with the presence of key metabolic comorbidities and increased postoperative morbidity and may be superior to BMI for risk stratification.

Circulating exosomes in the blood are promising tools for biomarker discovery in cancer. Due to their heterogeneity, different isolation methods may enrich distinct exosome cargos generating different omic profiles. In this study, we evaluated the effects of plasma exosome isolation methods on detectable multi-omic profiles in patients with non-small cell lung cancer (NSCLC), castration-resistant prostate cancer (CRPC), and healthy controls, and developed an algorithm to quantify exosome enrichment. Plasma exosomes were isolated from CRPC (n = 10), NSCLC (n = 14), and healthy controls (n = 10) using three different methods: size exclusion chromatography (SEC), lectin binding, and T-cell immunoglobulin domain and mucin domain-containing protein 4 (TIM4) binding. Molecular profiles were determined by mass spectrometry of extracted exosome fractions. Enrichment analysis of uniquely detected molecules was performed for each method with MetaboAnalyst. The exosome enrichment index (EEI) scores methods based on top differential molecules between patient groups. The lipidomic analysis detected 949 lipids using exosomes from SEC, followed by 246 from lectin binding and 226 from TIM4 binding. The detectable metabolites showed SEC identifying 191 while lectin binding and TIM4 binding identified 100 and 107, respectively. When comparing uniquely detected molecules, different methods showed preferential enrichment of different sets of molecules with SEC enriching the greatest diversity. Compared to controls, SEC identified 28 lipids showing significant difference in NSCLC, while only 1 metabolite in NSCLC and 5 metabolites in CRPC were considered statistically significant (FDR < 0.1). Neither lectin-binding- nor TIM4-binding-derived exosome lipids or metabolites demonstrated significant differences between patient groups. We observed the highest EEI from SEC in lipids (NSCLC: 871.33) which was also noted in metabolites. These results support that the size exclusion method of exosome extraction implemented by SBI captures more heterogeneous exosome populations. In contrast, lectin-binding and TIM4-binding methods bind surface glycans or phosphatidylserine moieties of the exosomes. Overall, these findings suggest that specific isolation methods select subpopulations which may significantly impact cancer biomarker discovery.

The current literature on depression within HIV populations shows poorer outcomes for these individuals than those in the general population. To further these studies, I performed an analysis looking at the effects of formal and informal social support on an HIV population in the south. The data comes from a 2005 SAMHSA study of health outcomes of 320 HIV-positive individuals over a twelve month period. The individuals in this study were referred through an enhanced substance abuse program. Social support variables used included professional support, support from a partner, support from family and friends, and feelings of closeness to family and friends. Depression was measured in the study as the number of days depressed in the past 30 days. This variable was recoded into categories for the analysis in this paper. Regression analysis was used and findings showed variations in the effects of different forms of social support. Both formal and informal social support variables were found to have no significant effect on people living with HIV/AIDS. Race was found to be significant for levels of depression reported. Implications of this study could help to better future outcomes for individuals within this population.

Background Motor challenges are highly prevalent within autism, and increased postural sway has been consistently demonstrated in autistic youth. However, the extent to which sway anomalies extend into adulthood remains understudied. This study aimed to investigate whether increased postural sway is altered in autistic adults compared to neurotypical controls using established sway metrics including sway area and path, as well as rambling-trembling decomposition—an approach that differentiates the postural sway signal into central and peripheral nervous system components. Methods 49 adults with autism spectrum conditions (ASC) and 94 neurotypical controls (NC) participated in a postural sway task on a force platform with manipulations of visual input and stance width. Traditional geometric methods (sway area and path), the spatial characteristics of the body’s adjustment to maintain balance, were measured. As resulting sway measures often covary, multiple factor analysis (MFA) was applied to reduce the measures into distinct, non-redundant dimensions that simplified the data. Group comparisons were completed across these different levels of analysis. Results We observed increased sway path and medio-lateral trembling in ASC compared to NC ( p  < 0.05). Significant group by vision interactions revealed that ASC sway increases were more apparent in eyes-open conditions for sway area and rambling and trembling in the anterior-posterior plane ( p  < 0.01), possibly suggesting differential sensory reweighting of visual input by ASC, or difficulties with multisensory integration. MFA revealed two key dimensions. A fast frequency dimension, linked to peripheral processes, explained most of the overall variance (62.9%) and captured more variance in the ASC group than in NC. A slower frequency dimension, linked to central processes, explained 8.0% of the variance. Limitations Order of sway conditions was consistent among all participants, so it is possible that participant fatigue influenced later sway conditions. Conclusions Building upon previous research finding increased postural sway in autism, we found that combining multiple approaches collectively suggest the critical role of peripheral contributions and visual input in postural sway in autism. Fast-frequency processes that are peripherally-driven may be of particular importance in sway in autistic adults, and should be prioritized in future research to better understand balance performance in autism.

Somatic mutations in KRAS are a common driver of colorectal cancer (CRC) and present at different frequencies by race, sex, tumor site, ethnicity, and genetic similarity. Inherited germline variants may influence tumor somatic mutation frequency by altering mutation or DNA repair processes or altering cellular, immunological and/or microenvironmental responses after a mutation. We hypothesized that the germline genetic background modifies somatic KRAS mutation frequency in CRC. To test this, we performed a genome-wide association study (GWAS) in 7071 individuals with CRC, using KRAS mutation status as the phenotype. Single-nucleotide variants were chosen for validation analyses based on P values from the discovery GWAS, predicted in silico functional effects, and proximity to genes with potential cancer relevance. A validation analysis of 101 SNVs of interest was performed in 2482 individuals. No SNVs were significantly associated with KRAS -mutant CRC ( P value < 0.0005). One variant rs73067863-T showed a non-significant exploratory association with fewer KRAS -mutant tumors in the combined sample ( P value = 9.7 × 10 –7 , OR = 0.75). Follow-up studies are needed to determine if these or other germline variants impact population differences in KRAS mutations in CRC.

Purpose Colorectal cancer (CRC) incidence and mortality are increasing among young adults (YAs) aged 18–39. This study compared quality of life (QOL) between YA and older adult CRC survivors in the ColoCare Study. Methods Participants were grouped by age (years) as follows: 18–39 (YA), 40–49, 50–64, and 65 + . Functional QOL (physical, social, role, emotional, cognitive) and global QOL were assessed with the EORTC-QLQ-C30 at enrollment, 3, 6, and 12 months. Average scores were compared between groups over time using longitudinal mixed-effect modeling. Proportions with clinically meaningful QOL impairment were calculated using age-relevant thresholds and compared between groups over time using logistic regression with mixed effects. Results Participants ( N  = 1590) were n  = 81 YAs, n  = 196 aged 40–49, n  = 627 aged 50–64, and n  = 686 aged 65 + . Average physical function was better among YAs than participants aged 50–64 ( p  = 0.010) and 65 + ( p  < 0.001), and average social function was worse among YAs than aged 65 + ( p  = 0.046). Relative to YAs, all age groups were less likely to report clinically meaningful social dysfunction (aged 40–49 OR = 0.13, 95%CI = 0.06–0.29; aged 50–64 OR = 0.10, 95%CI = 0.05–0.21; aged 65 + OR = 0.07, 95%CI = 0.04–0.15) and role dysfunction (aged 40–49 OR = 0.36, 95%CI = 0.18–0.75; aged 50–64 OR = 0.41, 95%CI = 0.22–0.78; aged 65 + OR = 0.32, 95%CI = 0.17–0.61). Participants aged 40–49 were also less likely to report physical dysfunction (OR = 0.42, 95%CI = 0.19–0.93). Conclusion YA CRC survivors reported better physical and worse social function compared to older CRC survivors, and YA CRC survivors were more likely to report clinically meaningful social, role, and physical disfunction. Future work should further investigate QOL using age-relevant benchmarks to inform best practices for CRC survivorship care. Trial registration NCT02328677, registered December 2014.