Citations

Abstract Transgender and gender-diverse (TGD) individuals face unique challenges in accessing affirming, evidence-based breast imaging care because of longstanding disparities in provider education, institutional practices, and imaging guidelines. Gender-affirming hormone therapy and gender-affirming surgeries, such as chest masculinization or breast augmentation, impact breast tissue composition and cancer risk, necessitating individualized imaging approaches. Through multiple clinical vignettes, this article illustrates potential pitfalls and key considerations in breast imaging for TGD patients, including appropriate imaging recommendations, inclusive system-level changes, and navigating patient encounters. Education of breast imaging radiologists, technologists, and front-desk staff is critical to bridge the known knowledge gap and improve outcomes for this patient population. By adopting inclusive, culturally competent, and trauma-informed practices, breast imaging professionals can help reduce disparities and improve the experience and health outcomes of TGD patients.

Abstract With the rapid advancements in large language model technology and the emergence of bioinformatics‐specific language models (BioLMs), there is a growing need for a comprehensive analysis of the current landscape, computational characteristics, and diverse applications. This survey aims to address this need by providing a thorough review of BioLMs, focusing on their evolution, classification, and distinguishing features, alongside a detailed examination of training methodologies, datasets, and evaluation frameworks. We explore the wide‐ranging applications of BioLMs in critical areas such as disease diagnosis, drug discovery, and vaccine development, highlighting their impact and transformative potential in bioinformatics. We identify key challenges and limitations inherent in BioLMs, including data privacy and security concerns, interpretability issues, biases in training data and model outputs, and domain adaptation complexities. Finally, we highlight emerging trends and future directions, offering valuable insights to guide researchers and clinicians toward advancing BioLMs for increasingly sophisticated biological and clinical applications.

Abstract Background Lung adenocarcinoma in never-smokers is a major public health burden, especially among East Asian women. Polygenic risk scores (PRSs) are promising for risk stratification but are primarily developed in European-ancestry populations. We aimed to develop and validate single- and multi-ancestry PRSs for East Asian never-smokers to improve lung adenocarcinoma risk prediction. Methods PRSs were developed using genome-wide association study summary statistics from East Asian (8002 cases; 20 782 controls) and European (2058 cases; 5575 controls) populations. Single-ancestry models included a PRS with 25 single nucleotide variants (PRS-25), PRS clumping and thresholding (CT), and LDpred2; multi-ancestry models included LDpred2 plus European PRS-128, PRS-CSx, and clumping and thresholding, super learning, empirical Bayes (CT-SLEB). Performance was evaluated in independent East Asian data from the Female Lung Cancer Consortium and externally validated in the Nanjing Lung Cancer Cohort. We assessed predictive accuracy via area under the curve operating procedure (AUC), with 10-year and (ages 30-80 years) absolute risks estimates. Results The best multi-ancestry PRS, using East Asian and European data via CT-SLEB, outperformed the best East Asian-only (LDpred2; AUC = 0.629, 95% confidence interval [CI] = 0.618 to 0.641), achieving an AUC of 0.640 (95% CI = 0.629 to 0.653) and odds ratio of 1.71 (95% CI = 1.61 to 1.82) per standard deviation increase. Nanjing Lung Cancer Cohort validation confirmed robust performance (AUC = 0.649, 95% CI = 0.623 to 0.676). The top 20% PRS group had a 3.92-fold higher lung adenocarcinoma risk than the bottom 20%. Further, the top 5% PRS group reached a 6.69% lifetime absolute risk. Notably, this group reached the average population 10-year lung adenocarcinoma risk at age 50 years (0.42%) by age 41 years, 9 years earlier. Conclusions Multi-ancestry PRS approaches enhance lung adenocarcinoma risk stratification in East Asian never-smokers, with consistent external validation, suggesting future clinical utility.

Abstract Frailty is highly prevalent in cardiovascular disease and associates with poor clinical outcomes. Several cardiovascular conditions benefit from invasive interventions, but the impact of these procedures in frail patients remains unclear. We thus performed a systematic review and meta-analysis to summarize evidence and quantify the pooled effect of clinical outcomes of invasive cardiovascular interventions among frail vs. non-frail patients. Systematic search of two electronic databases from January 2015 to April 2025 was performed including all randomized controlled trials (RCTs) and prospective cohort studies examining outcomes of invasive cardiovascular interventions stratified by frailty. Outcomes included all-cause mortality, hospitalizations, and other adverse outcomes. Risk ratios (RRs) and their 95% confidence intervals (CI) were assessed using random-effects models. Thirty-one studies (10 RCTs, 21 prospective, 3 retrospective studies) with a total of 27 534 participants were included. Compared with non-frail patients, frail patients after cardiovascular procedures were at higher risks of all-cause mortality (RR 3.14, 95% CI: 2.29-4.30), and hospitalizations (RR 1.88, 95% CI: 1.29-2.73). Frail patients undergoing transcatheter aortic-valve implantation and percutaneous mitral-valve interventions did not have significant increased mortality risks compared with non-frail patients (P > 0.05). Pre-frailty predicted lower mortality risks amongst patients undergoing transcatheter vs. surgical aortic valve replacement (HR 0.78, 95% CI: 0.67-0.92). Frail patients with non-ST elevation myocardial infarction derived similar mortality benefits from an invasive vs. conservative approach (HR 1.13, 95% CI: 0.64-2.01). In conclusion, frailty prognosticates adverse outcomes following invasive cardiovascular interventions and influences treatment efficacy, highlighting its significance in treatment selection

Abstract INTRODUCTION We investigated associations of plasma proteins with blood‐based amyloid/tau/neurodegeneration/inflammation (A/T/N/I) biomarkers for Alzheimer's disease (AD). METHODS Plasma proteomics and clinical data from the Indiana AD Research Center ( N = 498) were used. Association analysis of plasma proteins with blood A/T/N/I biomarkers as well as diagnosis was performed, followed by replication in an independent cohort ( N = 323), network analysis, pathway enrichment, and machine learning classification to identify proteins and pathways related to AD risk. RESULTS We identified 35 proteins associated with AD, 20 of which were replicated in the independent cohort. We identified 150, 448, and 219 proteins associated with T/N/I biomarkers, respectively, revealing biomarker‐specific pathways. Network analysis identified two modules associated with T/N/I biomarkers, preserved in cerebrospinal fluid (CSF), and their enriched pathways. The classification model of proteins effectively differentiated AD (area under the curve [AUC] = 0.930). CONCLUSION Our findings suggest dysregulated plasma proteins and pathways in AD, enhancing our understanding of molecular mechanisms and diagnostic strategies for AD. Highlights Plasma proteins were identified as being associated with Alzheimer's disease (AD) and plasma biomarkers. The identified proteins were replicated in both plasma and cerebrospinal fluid (CSF) proteomics. The identified proteins were associated with AD biomarker‐specific pathways. The identified proteins improved the performance of the AD classification. Protein network analysis identified network modules and their enriched pathways.

Abstract INTRODUCTION Mitochondrial dysfunction is implicated in Alzheimer's disease (AD), but whether it drives AD‐associated changes is unclear. We assessed transcriptomic alterations in the brains of Ndufs4 −/− mice, a model of mitochondrial complex I (mtCI) deficiency, and evaluated the therapeutic effects of the neuroprotective mtCI inhibitor CP2. METHODS Cortico‐hippocampal tissue from Ndufs4 −/− and wild‐type mice was subjected to transcriptomic analysis, followed by cross‐species comparisons to human late‐onset AD and familial AD mouse datasets. RESULTS Knockout of Ndufs4 ‐mediated mtCI deficiency disrupted mitochondrial homeostasis, energy metabolism, and synaptic gene expression, recapitulating transcriptomic signatures of AD. CP2 treatment partially reversed these changes, with female Ndufs4 −/− mice showing greater compensatory adaptations and treatment responses. DISCUSSION Loss of mtCI activity alone is sufficient to induce AD‐like molecular changes in the brain, independent of amyloid beta or phosphorylated tau. CP2‐mediated rescue highlights the potential of targeting mitochondria as a therapeutic strategy for AD. Sex‐specific responses suggest important considerations for personalized therapeutics. Highlights Activity of mitochondrial complex I (mtCI) affects broad mitochondrial and neuronal transcriptional networks. A reduction of mtCI activity is sufficient to induce transcriptomic changes reminiscent of those observed in late‐onset Alsheimer's disease (AD) patients and familial mouse models of AD. Pharmacological targeting of mtCI mediates neuroprotective signaling. Male and female mice have differential responses to the loss of mtCI activity and to the mitochondria‐targeted therapeutics. Mitochondria play a key role in AD development and treatment.

Abstract Background We retrospectively assessed volumetric response of myxoid liposarcoma (MLPS) with preoperative radiotherapy (RT) and sought to identify disease and treatment characteristics associated with response. Patients and methods We identified all patients with a histologic diagnosis of MLPS who received preoperative RT from 2013 to 2021 at our institution. We used cone beam computed tomography (CBCT) to assess changes in tumor volume and greatest dimension during treatment. Tumors were contoured on CBCT images prior to treatment and at the end of each week of RT. Percentage change in tumor volume and greatest dimension were calculated based on pre-treatment and final week contours. Patients with tumors incompletely visualized on CBCT were excluded from volume analysis but included on greatest dimension analysis. Magnetic resonance imaging (MRI) was used to evaluate pre- and post-RT radiographic features. Surgical pathology was reviewed to record pathologic characteristics. Results Twenty patients met inclusion criteria. Most tumors (18/20) were low grade. The most frequent dose/fractionation scheme was 50 Gy in 25 fractions (16/20), with 3 patients receiving 36 Gy in 18 fractions. Median pre-RT volume and greatest dimension were 120 cc (interquartile range [IQR]: 56–399) and 11.2 cm (IQR: 8.4–14.1), respectively. Median percentage change in volume and greatest dimension were -37% (IQR: -57 to -29) and -10% (IQR: -20 to -7). All evaluable tumors decreased in volume during RT. Between pre- and post-RT MRI, most patients had a decrease in intratumoral (16/20) and peritumoral edema (11/20). Sixteen patients exhibited extensive pathologic response. There were no significant associations between radiographic and pathologic features and volumetric change. Local failure at 3 years was 9% (95% confidence interval: 1–59). Conclusions We report significant decreases in MLPS tumor size during preoperative RT. There may be a role for adaptive RT planning to reduce target volumes and minimize RT-associated morbidity.

PURPOSE Tumor treating fields (TTFields) use alternating electric fields to disrupt cancer cell proliferation. Feasibility of TTFields therapy with gemcitabine/nab-paclitaxel was previously demonstrated in patients with advanced pancreatic adenocarcinoma. PANOVA-3 was designed to confirm safety and efficacy of TTFields in patients with unresectable locally advanced pancreatic adenocarcinoma (LA-PAC). METHODS In this global phase III trial, 571 patients with newly diagnosed LA-PAC were randomly assigned to receive gemcitabine 1,000 mg/m 2 and nab-paclitaxel 125 mg/m 2 by intravenous infusion once a day on days 1, 8, and 15 of a 28-day cycle with or without TTFields. The primary end point was overall survival (OS). Secondary end points included progression-free survival (PFS), local PFS, pain-free survival, and overall response rate (ORR). Distant PFS was analyzed post hoc. RESULTS OS was significantly prolonged using TTFields with gemcitabine/nab-paclitaxel versus gemcitabine/nab-paclitaxel (median, 16.2 months [95% CI, 15.0 to 18.0] v 14.2 months [95% CI, 12.8 to 15.4]; hazard ratio [HR], 0.82 [95% CI, 0.68 to 0.99]; P = .039). PFS, local PFS, and ORR were not improved. Pain-free survival was significantly prolonged with TTFields with gemcitabine/nab-paclitaxel (median, 15.2 months [95% CI, 10.3 to 22.8] v 9.1 months [95% CI, 7.4 to 12.7]; HR, 0.74 [95% CI, 0.56 to 0.97]; P = .027), as was distant PFS (median, 13.9 months [95% CI, 12.2 to 16.8] v 11.5 months [95% CI, 10.4 to 12.9]; HR, 0.74 [95% CI, 0.57 to 0.96]; P = .022). Device-related skin adverse events (AEs) were experienced by 76.3% of patients. Most device-related skin AEs were mild to moderate, with 7.7% of patients reporting a grade 3 AE. CONCLUSION This study demonstrated significant OS, pain-free survival, and distant PFS benefits for TTFields with gemcitabine/nab-paclitaxel versus gemcitabine/nab-paclitaxel in patients with unresectable LA-PAC, with no additive systemic toxicity.