First-Line PD-1 Blockade Combined With Chemotherapy for Stage IV Penile Squamous Cell Carcinoma: A Multicenter Retrospective Study.

Background: The purpose of this study was to evaluate the efficacy and safety of PD-1 blockade combined with cisplatin and paclitaxel (TP)-based chemotherapy as first-line treatment for advanced penile squamous cell carcinoma (PSCC).

Patients And Methods: A retrospective review was performed of 32 eligible patients with high-risk stage IV (cN3M0-1) PSCC who received first-line PD-1 blockade combined with TP-based chemotherapy at 5 medical centers (2019-2023). Clinical responses were assessed using RECIST version 1.

PARP1 promotes tumor proliferation in lenalidomide-resistant multiple myeloma via the downregulation of microRNA-192-5p-AKT signaling.

Background: Lenalidomide-based therapies are recommended as first-line treatment for multiple myeloma (MM) patients, regardless of the transplant eligibility. Resistance to lenalidomide is a clinical problem that urgently needs to be addressed. The expression of poly(ADP-ribose) polymerase 1 (PARP1) is abnormally high in a variety of tumor tissues including MM.

Physical activity and incident cardiovascular disease in breast cancer survivors: the pathways study.

Purpose: Breast cancer survivors experience higher rates of cardiovascular disease (CVD) than women without breast cancer, due in part to cardiotoxic cancer treatments and shared lifestyle risk factors. Physical activity is associated with lower mortality risk in breast cancer survivors, but associations with CVD have not been examined in detail.

Methods: The Pathways Study is a prospective cohort study of 4,504 women diagnosed with invasive breast cancer between 2005 and 2013.

Imaging NRF2 activation in non-small cell lung cancer with positron emission tomography.

Mutations in the NRF2-KEAP1 pathway are common in non-small cell lung cancer (NSCLC) and confer broad-spectrum therapeutic resistance, leading to poor outcomes. Currently, there is no means to non-invasively identify NRF2 activation in living subjects. Here, we show that positron emission tomography imaging with the system x radiotracer, [F]FSPG, provides a sensitive and specific marker of NRF2 activation in orthotopic, patient-derived, and genetically engineered mouse models of NSCLC.

Differential Infiltration of Key Immune T-Cell Populations Across Malignancies Varying by Immunogenic Potential and the Likelihood of Response to Immunotherapy.

Solid tumors vary by the immunogenic potential of the tumor microenvironment (TME) and the likelihood of response to immunotherapy. The emerging literature has identified key immune cell populations that significantly impact immune activation or suppression within the TME. This study investigated candidate T-cell populations and their differential infiltration within different tumor types as estimated from mRNA co-expression levels of the corresponding cellular markers.

Changes in Skin Cancer-Related Behaviors, Distress, and Beliefs in Response to Receipt of Low- to Moderate-Penetrance Genetic Test Results for Skin Cancer Risk.

Little is known about the impact of low- to moderate-penetrance genetic testing for skin cancer, which is a promising approach to skin cancer prevention. To address this deficit, we conducted an analysis comparing changes in skin cancer-related behaviors, distress, and beliefs measured at a baseline and twice after the receipt of skin cancer precision prevention materials containing risk feedback (higher or average risk) among 568 non-Hispanic White (NHW) and 463 Hispanic participants. Regression analyses identified decreased average weekend hours in the sun (β = -0.

Exploring Genomic Biomarkers for Pembrolizumab Response: A Real-World Approach and Patient Similarity Network Analysis Reveal DNA Response and Repair Gene Mutations as a Signature.

: Single-agent immune checkpoint inhibitor (IO) therapy is the standard for non-oncogene-addicted advanced non-small cell lung cancer (aNSCLC) with PD-L1 tumor proportion score ≥ 50%. Smoking-induced harm generates high tumor mutation burden (H-TMB) in smoking patients (S-pts), while never-smoking patients (NS-pts) typically have low TMB (L-TMB) and are unresponsive to IO. However, the molecular characterization of NS-pts with H-TMB remains unclear.

Effects of Socioeconomic Deprivation on UTUC Staging, Mortality, and Recurrence.

Objectives: To determine whether the area deprivation index (ADI), a surrogate for socioeconomic status (SES) associated with patient residence, affected UTUC staging, recurrence rates, and mortality.

Methods: Patients undergoing radical nephroureterectomy or ureterectomy for UTUC at a single institution between February 2010 to August 2021 were classified by ADI. A 50 percentile cut-off of ADI classified patients as "advantaged" or "disadvantaged.

TBK1 Reprograms Metabolism in Breast Cancer: An Integrated Omics Approach.

Metabolic rewiring is required for cancer cells to survive in harsh microenvironments and is considered to be a hallmark of cancer. Specific metabolic adaptations are required for a tumor to become invasive and metastatic. Cell division and metabolism are inherently interconnected, and several cell cycle modulators directly regulate metabolism.

The impact of the Turkish population variome on the genomic architecture of rare disease traits.

Purpose: The variome of the Turkish (TK) population, a population with a considerable history of admixture and consanguinity, has not been deeply investigated for insights on the genomic architecture of disease.

Methods: We generated and analyzed a database of variants derived from exome sequencing data of 773 TK unrelated, clinically affected individuals with various suspected Mendelian disease traits and 643 unaffected relatives.

Results: Using uniform manifold approximation and projection, we showed that the TK genomes are more similar to those of Europeans and consist of 2 main subpopulations: clusters 1 and 2 ( = 235 and 1181, respectively), which differ in admixture proportion and variome (https://turkishvariomedb.

Primary retroperitoneal lymph node dissection in clinical stage 2a/b non-seminomatous germ cell tumour.

Objectives: To reassess the role of primary retroperitoneal lymph node dissection (RPLND) in patients with marker-negative non-seminomatous germ cell tumour (NSGCT) clinical stage (CS) 2a, to explore results in patients with CS 2b and to evaluate surgical methods, recurrence, and adjuvant chemotherapy indications.

Materials And Methods: Data from 17 institutions were collected, comprising 305 men who underwent primary RPLND for CS 2 NSGCT. Regression analyses were conducted to predict histology in the RPLND specimen and disease-free survival (DFS).

Exploring aggregation genes in a chronic infection model.

Unlabelled: Bacterial aggregates are observed in both natural and artificial environments. In the context of disease, aggregates have been isolated from chronic and acute infections. () aggregates contribute significantly to chronic infections, particularly in the lungs of people with cystic fibrosis (CF).

Radiomic features of PET/CT imaging of large B cell lymphoma lesions predicts CAR T cell therapy efficacy.

Background: Relapsed and refractory Diffuse large B cell lymphoma (DLBCL) can be successfully treated with axicabtagene ciloleucel (axi-cel), a CD19-directed autologous chimeric antigen receptor T cell (CAR-T) therapy. Diagnostic image-based features could help identify the patients who would clinically respond to this advanced immunotherapy.

Purpose: The aim of this study was to establish a radiomic image feature-based signature derived from positron emission tomography/computed tomography (PET/CT), including metabolic tumor burden, which can predict a durable response to CAR-T therapy in refractory/relapsed DLBCL.

Tumor burden quantified by Soluble B-Cell Maturation Antigen and Metabolic Tumor Volume determine myeloma CAR-T outcomes.

Chimeric antigen receptor T-cell (CAR-T) therapy has emerged as a breakthrough treatment for relapsed and refractory multiple myeloma (RRMM). However, these products are complex to deliver and alternative options are now available. Identifying biomarkers that can predict therapeutic outcomes is crucial for optimizing patient selection.

Identifying targeted cell-free DNA methylation regions in head and neck cancer via paired methylome analysis.

Despite the critical need, progress in developing cell-free DNA (cfDNA) liquid biopsy biomarkers for the diagnosis and risk stratification of head and neck squamous cell carcinoma (HNSC) has been limited. In this study, we present a comprehensive paired-sample differential methylation region (psDMR) analysis in HNSC, aimed at identifying reliable and HNSC-specific regions for cfDNA biomarker discovery. Traditional DMR analyses often overlook paired-sample information and fail to account for the heterogeneity within HNSC tissues.

A computational approach to matching multiple sclerosis-related, IGH CDR3s with a MBP epitope.

In multiple sclerosis (MS), T-cell receptors (TCRs) and antibodies specifically target the main structural proteins of myelin, including myelin basic protein (MBP), especially a specific, canonical, immunoglobulin (IG)-targeted MBP epitope. Efficient computational analyses to diagnose or monitor autoimmune conditions, which could have broad applicability in clinical trials or in diagnoses, remains a challenge. As such, we considered the possibility that focusing on the immunoglobin heavy chain (IGH) complementarity determining region-3 (CDR3) amino acid sequences could support the development of an efficient, convenient, and user-friendly approach to detecting or assessing IGH targets in MS.

spatialGE is a User-Friendly Web Application that Facilitates Spatial Transcriptomics Data Analysis.

Spatial transcriptomics (ST) is a powerful tool for understanding tissue biology and disease mechanisms. However, the advanced data analysis and programming skills required can hinder researchers from realizing of the full potential of ST. To address this, we developed spatialGE, a web application that simplifies the analysis of ST data.

Vision-language models for medical report generation and visual question answering: a review.

Medical vision-language models (VLMs) combine computer vision (CV) and natural language processing (NLP) to analyze visual and textual medical data. Our paper reviews recent advancements in developing VLMs specialized for healthcare, focusing on publicly available models designed for medical report generation and visual question answering (VQA). We provide background on NLP and CV, explaining how techniques from both fields are integrated into VLMs, with visual and language data often fused using Transformer-based architectures to enable effective learning from multimodal data.

The Effect of Health Insurance on Racial Disparities in Patients With Isolated Colorectal Liver Metastases.

Background And Objectives: Although resection of colorectal liver metastases (CRLM) improves survival, factors including race and health insurance are associated with disparities in care. The aim of this study was to evaluate the effect of health insurance on racial disparities in CRLM resection.

Methods: A retrospective study of patients with CRC with synchronous CRLM was performed using the National Cancer Database (2004-2020).