Citations

Breast cancer is the most prevalent cancer among women and is challenging to diagnose and treat due to its diverse subtypes and stages. Precision medicine aims to improve early detection, prognosis, and treatment planning by identifying new clinical biomarkers. The review emphasizes the importance of using cutting-edge technology and artificial intelligence (AI) to identify new biomarkers associated with epithelial–mesenchymal transition (EMT). During EMT, epithelial cells transform into a mesenchymal state, a process driven by genetic and epigenetic alterations that facilitate cancer progression. The review discusses how statistical analysis and machine learning methods applied to multi-omics data facilitate the discovery of novel EMT-related biomarkers, thereby advancing therapeutic strategies. This conclusion is supported by numerous clinical and preclinical studies on breast cancer.

ABSTRACT Background Chronic gastroduodenal symptoms arise from heterogeneous gastric motor dysfunctions. This study applied multimodal physiological testing using gastric emptying scintigraphy (GES) with intragastric meal distribution (IMD) and Gastric Alimetry body surface gastric mapping (BSGM) to define motility and symptom associations. Methods Patients with chronic gastroduodenal symptoms underwent simultaneous supine GES and BSGM with a 30 m baseline, 99mTC‐labeled egg meal, and 4 h postprandial recording. IMD (ratio of counts in the proximal half of the stomach to the total gastric counts) was calculated immediately after the meal (IMD0), with < 0.568 defining abnormal IMD. BSGM phenotyping followed a consensus approach, based on normative spectral reference intervals. Results Among 67 patients (84% female, median age 40 years, median BMI 24 kg/m 2 ), median IMD0 was 0.76 (IQR: 0.69–0.86) with 5 (7.5%) meeting abnormal IMD criteria. Delayed gastric emptying ( n = 18) was associated with higher IMD0 (median 0.9 vs. 0.7, p = 0.004). On BSGM, 15 patients had abnormal spectrograms (5 [7.5%] high frequency and 10 [14.9%] low rhythm stability and/or amplitude); and in these patients, higher IMD0 (proximal retention) strongly correlated to delayed BSGM meal responses ( R = −0.71, p = 0.003). Lower IMD, indicating antral distribution, correlated with higher gastric frequencies ( R = −0.27, p = 0.03). BSGM abnormalities paired with abnormal IMD were associated with worse dyspeptic symptoms. Conclusion Proximal retention of food as assessed by IMD correlated with delayed emptying, and in the presence of neuromuscular spectral abnormalities (abnormal frequencies or rhythms), delayed motility responses on BSGM. Patients with multiple motor abnormalities experience worse dyspeptic symptoms.

Abstract Objective The goal of this study was to examine if differing platelet counts in platelet‐rich plasma (PRP) formulations affected overall pain and function outcomes when compared to hyaluronic acid or placebo control saline injections. Design/Methods We conducted a systematic review and meta‐analysis (International Prospective Register of Systematic Reviews CRD42022340057) evaluating randomized controlled trials comparing injections of PRP to hyaluronic acid (HA) or saline (NS) control in patients with mild or moderate knee osteoarthritis. All studies used a validated outcome measure that examined pain, function, or overall patient global assessment. Study PRP interventions were subclassified as investigating the total number of platelets delivered in a low dose (1–5 billion total deliverable platelets), moderate dose (5–10 billion total deliverable platelets), or high dose (greater than 10 billion total deliverable platelets) injected into the joint. Results A total of 32 trials met inclusion criteria. All three PRP groups had significant improvements in validated patient‐reported outcomes when compared to HA. Both the “low” and “high” platelet count groups resulted in a moderate effect size, respectively (standardized mean difference [SMD] = .47; 95% confidence interval [CI] .05–0.89, p < .01; SMD = .68; 95% CI .26–1.09, p < .01). Only the “moderate” (SMD = 1.48; 95% CI .71–2.58 p < .01) platelet count group resulted in large effect size on validated patient‐reported outcomes. When compared to NS, all three PRP groups resulted in significant large effect sizes when examining pain reduction. Conclusions When compared to HA, PRP with platelet counts between 1 and 10 billion total deliverable platelets may result in a larger decrease in pain symptoms when compared to platelet counts greater than 10 billion at 6 months. In addition, platelet counts between 5 and 10 billion total deliverable platelets may be associated with greater improvement in functional outcomes.

Background: Metabolic and bariatric surgery (MBS) is an established treatment for severe obesity and its related comorbidities. While long-term outcomes are often emphasized, early postoperative complications remain a critical metric of safety and resource utilization. Large database studies have reported national trends in MBS outcomes but are limited by lack of granularity, inconsistent definitions, and inclusion of heterogeneous surgical experience. This study aimed to provide a detailed analysis of 30-day postoperative complications following sleeve gastrectomy (SG), Roux-en-Y gastric bypass (RYGB), and duodenal switch (DS) over a 17-year period at a single high-volume quaternary academic center. Materials and Methods: A retrospective cohort study of adult patients who underwent primary laparoscopic SG, RYGB, or DS between 2008 and 2024. All procedures were performed by fellowship-trained, minimally invasive bariatric surgeons. Complications occurring within 30 days postoperatively were identified through comprehensive chart review and classified using the Clavien-Dindo grading system. Primary outcomes included incidence, severity, and type of complications, as well as rates of readmission, reoperation, and reintervention. Multivariable logistic regression was used to identify predictors of overall and major complications. Results: Of 2190 patients included, 413 (18.9%) experienced at least 1 early complication, totaling 467 discrete events. DS had the highest complication rate (29.3%), followed by RYGB (18.4%) and SG (17.5%). RYGB was associated with a high burden of major complications, including anastomotic strictures, GI bleeding, and reoperations for obstruction or leak. The 30-day rates of readmission (2.0%) and reoperation (1.3%) were low across all groups. Independent predictors of major complications included venous stasis (aOR=3.22), renal insufficiency (aOR=2.65), and type 2 diabetes (aOR=1.96); both RYGB (aOR=2.25) and DS (aOR=2.77) carried higher risk than SG. Conclusion: This study provides a granular, procedure-specific profile of early complications after SG, RYGB, and DS. While all 3 procedures demonstrated acceptable safety profiles, DS had the highest overall complication rate, and RYGB carried the greatest burden of major complications. These findings underscore the variability in early postoperative outcomes by procedure type and reflect the value of institutional experience in characterizing complication profiles.

Objectives Directly compare the brain glucose patterns seen with [F‐18] fluorodeoxyglucose (FDG) positron emission tomography (PET) between 2 genetically determined forms of Alzheimer's disease: Down syndrome (DS) and autosomal dominant Alzheimer's disease (ADAD). Methods Cross‐sectional analyses of FDG were performed in individuals with DS (n = 76) from the Alzheimer Biomarker Consortium‐Down Syndrome (ABC‐DS), ADAD (n = 297), and neurotypical familial controls (n = 188) from the Dominantly Inherited Alzheimer Network (DIAN). Within‐group linear regression models and generalized additive models were performed for select regional FDG uptake measures (isthmus cingulate and inferior parietal, precuneus, middle temporal gyrus, and precentral gyrus). Age, sex, apolipoprotein (APOE) ε4 carrier status, and cortical amyloid burden were included within these analyses. Results Even 20 years before expected onset of clinical symptoms, FDG uptake was lower for DS compared to neurotypical familial controls ( p < 0.01). ADAD baseline FDG was similar to neurotypical familial controls until 7 years before expected symptom onset. Both symptomatic individuals with DS and ADAD had lower FDG compared to neurotypical familial controls ( p < 0.01). A higher amyloid burden was associated with lower FDG for both genetic forms, with similar rates of decline in FDG uptake for DS and ADAD who were amyloid positive. Interpretation Brain glucose metabolism is substantially lower for people with DS, even in individuals who are cognitively stable. The patterns of FDG decline are distinct in these 2 genetically determined forms of AD. The diagnostic utility of FDG‐PET is specific to the genetic form of AD. ANN NEUROL 2025;98:1237–1248

Objective To establish a framework for validating candidate biomarkers of cerebral small vessel diseases (SVD) associated with cognitive impairment and characterize individuals enrolled by the MarkVCID2 consortium under this framework. Methods Participants age 60 to 90 years were enrolled across 17 MarkVCID2 sites. Recruitment was targeted to enrich in cognitive symptoms (mild dementia, mild cognitive impairment, subjective cognitive decline), defined risk factors (diabetes mellitus, advanced hypertension), and Black/African American, White, and Hispanic/Latino subgroups. Enrolled participants underwent baseline visits that included cognitive testing, multimodal magnetic resonance imaging (MRI), and biofluid collection. Provisional risk for SVD‐related cognitive decline was estimated primarily by baseline cognitive symptoms plus SVD risk factors. Adjudicated risk status was estimated by cognitive symptoms plus presence of moderate‐to‐severe white matter hyperintensities, microbleeds, or lacunes on baseline MRI. Results MarkVCID2 enrolled 1883 individuals age 73.4 ± 7.5 years, 65.0% female, 24.2% Hispanic, and 27.1% non‐Hispanic Black. Among enrollees, 44.8% were provisionally designated high‐risk. After baseline MRI, 48.5% were categorized as adjudicated high‐risk status, with substantial recategorization both from low‐ to high‐risk (primarily because of MRI lesions without SVD risk factors) and high‐ to low‐risk (primarily suspected cognitive impairment at screening not confirmed by baseline testing). Interpretation MarkVCID2 baseline data indicate successful enrollment of diverse individuals enriched in factors associated with SVD‐related cognitive decline. Changes over 3 years of longitudinal follow‐up will be analyzed to validate the candidate biomarkers for 2 projected contexts of use: subject selection (identifying likelihood of future SVD progression) and study outcome (efficiently measuring SVD progression). ANN NEUROL 2026;99:449–458

Abstract Objectives Hepatic steatosis impacts the quality of grafts, affecting transplant outcomes. Rising obesity rates and subsequent donor graft steatosis further influence the organ shortage crisis in pediatric liver transplantation (LT). Our study aimed to evaluate how donor steatosis modulates the outcomes of pediatric LT. Methods We analyzed the United Network of Organ Sharing database for transplanted donor grafts from January 01, 2004, to April 30, 2024. We stratified pediatric (≤18 years) LT recipients into steatotic grafts, subdivided into <30% and ≥30%. Graft failure was assessed using Kaplan–Meier curves, and Cox proportional hazards models, with Lasso regression identifying key predictive variables. Gradient‐boosting decision tree was used to assess the level of likelihood importance for post‐LT survival. Results Five hundred and ninety‐five pediatric LT recipients were included; 62 (10.4%) received donors with steatosis levels ≥30%. Survival rates for steatotic grafts ≥30% were 93.5% at 1 year, 89.9% at 5 years, and 84.4% at 10 years, compared to 94.7%, 89.5%, and 85.2% respectively, among steatotic grafts <30% ( p = 0.72, p = 0.92, and p = 0.92). Donor age (adjusted hazard ratio [aHR]: 1.01, 95% confidence interval [CI]: 1.01–1.03), donation after cardiac death (DCD) (aHR: 10.68, 95% CI: 3.27–34.86), and recipient life support (aHR: 1.95, 95% CI: 1.19–3.20) were associated with an increased risk of mortality. Conclusion Steatotic grafts in pediatric patients had acceptable outcomes. Predictors of mortality in steatotic grafts, including donor age, DCD, and recipient life support, underscore the complex interplay of multiple factors in post‐LT outcomes.

Abstract Mesenchymal stem cell (MSC)-derived exosomes are recognized as critical mediators within the tumor microenvironment (TME), exerting both pro- and anti-tumorigenic effects depending on contextual factors. These vesicles are also gaining attention for their potential as therapeutic vehicles in regenerative medicine and targeted drug delivery. However, the influence of the TME on the physical characteristics of MSC-derived exosomes remains poorly understood. In this study, we utilized Atomic Force Microscopy (AFM) to investigate the morphological and nanomechanical properties of MSC-derived exosomes under standard and TME-like conditions. AFM imaging in fluid mode preserved the native structure of exosomes and enabled high-resolution analysis of their topography, surface roughness, stiffness, adhesion, and deformation. AFM offers unique advantages in exosome research by enabling label-free, nanoscale analysis of vesicle properties in near-physiological conditions. The ability to detect such subtle but functionally significant changes highlights the relevance of AFM in exosome characterization and quality assessment. Our results revealed that exposure to the TME induces marked changes in exosomal membrane morphology and mechanical behavior, including increased surface heterogeneity, higher stiffness, and altered adhesive interactions. These biophysical alterations may reflect changes in membrane composition and protein or lipid cargo, potentially affecting exosome function, uptake, and therapeutic efficacy. Overall, our findings provide new insights into how the TME modulates MSC exosome biophysics and underscore the utility of AFM-based techniques for advancing the development of exosome-based diagnostics and therapies. This can provide a conceptual framework for future mechanistic and translational studies in this area.

Abstract Background Mitotane monotherapy is the standard adjuvant treatment for adrenocortical carcinoma (ACC), yet reliable predictors of treatment response remain lacking. Given the well-recognized interplay between inflammation and cancer progression, serum inflammation-based scores have shown prognostic significance in various malignancies, including ACC in palliative settings. However, their relevance during adjuvant mitotane therapy remains uncertain. This study aimed to assess the prognostic value of inflammation-scores in patients with ACC receiving adjuvant mitotane. Methods Multicenter ENSAT retrospective study including patients with ACC treated with adjuvant mitotane as first-line therapy. Clinical data including age, sex, ENSAT tumor stage, Ki67 index, resection status, and hormone secretion were collected at diagnosis. Inflammation-scores - neutrophil-to-lymphocyte ratio (NLR), derived NLR (dNLR), systemic immune inflammation index (SII), and pan-immune-inflammation value (PIV) - were calculated at diagnosis (pre-surgery) and at mitotane start. Median values of inflammation-scores at diagnosis defined low and high levels. Overall survival (OS) and time to progression (TTP) from mitotane start were the primary endpoints. Results The study included 395 patients (66% female; median age: 51 years). Median time to mitotane start was 54 days (IQR: 32–90). At diagnosis, patients with glucocorticoid excess (n=84) had significantly higher inflammation-scores than those without (n=104): NLR (3.61 vs 2.53), dNLR (2.31 vs 1.72), SII (864.1 vs 679.3), and PIV (531.6 vs 343.1); all p≤0.005. All scores significantly declined after surgery (p&lt;0.05). Higher inflammatory scores at diagnosis were associated with worse OS (NLR: HR=3.85, 95%CI=1.95–7.59, p&lt;0.001; dNLR: HR=3.19, 95%CI=1.67- 6.08, p&lt;0.001; SII: HR=1.97, 95%CI = 1.07–3.61, p=0.03; PIV: HR=2.11, 95%CI=1.13-3.95, p=0.02). However, only the NLR and dNLR remained independently associated with OS at multivariate analysis adjusted for ENSAT stage, Ki67 index, and resection status (p&lt;0.05). At mitotane start (n=372), high SII and PIV were associated with shorter TTP (SII: HR=1.36, 95%CI=1.02-1.82, p=0.03; PIV: HR=1.40, 95%CI=1.04-1-87, p=0.02), with only SII remaining significant at multivariate regression (p=0.04). Conclusions Inflammation-based scores are higher in patients with glucocorticoid excess and decrease postoperatively. NLR and dNLR at diagnosis, and SII at mitotane start, are associated with clinical outcomes in patients with ACC receiving mitotane adjuvant monotherapy. These readily available markers may help improve prognostic stratification in clinical practice.

Mood disorders are among the most disabling and complex psychiatric conditions, affecting millions worldwide and contributing substantially to morbidity, mortality, and healthcare utilization [...]