The spatial landscape of cancer hallmarks reveals patterns of tumor ecological dynamics and drug sensitivity.

Tumors are complex ecosystems of interacting cell types. The concept of cancer hallmarks distills this complexity into underlying principles that govern tumor growth. Here, we explore the spatial distribution of cancer hallmarks across 63 primary untreated tumors from 10 cancer types using spatial transcriptomics.

Revolutionizing acute myeloid leukemia treatment: a systematic review of immune-based therapies.

The established protocol for the management of acute myeloid leukemia (AML) has traditionally involved the administration of induction chemotherapy, followed by consolidation chemotherapy, and subsequent allogeneic stem cell transplantation for eligible patients. However, the prognosis for individuals with relapsed and refractory AML remains unfavorable. In response to the necessity for more efficacious therapeutic modalities, targeted immunotherapy has emerged as a promising advancement in AML treatment.

Encorafenib, cetuximab and chemotherapy in BRAF-mutant colorectal cancer: a randomized phase 3 trial.

Encorafenib + cetuximab (EC) is approved for previously treated BRAF V600E-mutant metastatic colorectal cancer (mCRC) based on the BEACON phase 3 study. Historically, first-line treatment of BRAF V600E-mutant mCRC with chemotherapy regimens has had limited efficacy. The phase 3 BREAKWATER study investigated EC+mFOLFOX6 versus standard of care (SOC) in patients with previously untreated BRAF V600E mCRC.

Clinically Meaningful Upstaging and Upgrading in Favorable Intermediate-Risk Radical Prostatectomy Patients.

Introduction: In NCCN favorable intermediate-risk (FIR) prostate cancer (PCa) patients treated with radical prostatectomy (RP), we tested the effect of upstaging and upgrading on cancer-specific mortality (CSM).

Methods: Within the SEER database (2010-2021), upstaging (≥pT3a or pN1) and upgrading (ISUP ≥3) rates in FIR RP patients were tabulated. Kaplan-Meier (KM) plots and multivariable Cox-regression models (CRMs) were fitted.

Assessing the performance of ChatGPT in medical ethical decision-making: a comparative study with USMLE-based scenarios.

Introduction: The integration of artificial intelligence (AI) into healthcare introduces innovative possibilities but raises ethical, legal and professional concerns. Assessing the performance of AI in core components of the United States Medical Licensing Examination (USMLE), such as communication skills, ethics, empathy and professionalism, is crucial. This study evaluates how well ChatGPT versions 3.

Imaging of Acute Pulmonary Embolism: An Update.

Imaging is essential in the evaluation and management of acute pulmonary embolism. Advances in multi-energy CT including dual-energy CT and photon-counting CT have allowed faster scans with lower radiation dose and optimal quality. Artificial intelligence has a potential role in triaging potentially positive examinations and could serve as a second reader.

Ultra-processed food consumption and risk of dementia and Alzheimer's disease: The Framingham Heart Study.

Background: Ultra-processed food consumption is emerging as a risk factor for various cardiometabolic diseases, however its association with dementia and Alzheimer's disease has rarely been explored.

Objectives: We sought to examine whether ultra-processed food consumption is associated with risk of all-cause dementia and Alzheimer's disease among middle-age and older adults.

Design: A prospective cohort study.

High definition transcranial direct current stimulation as an intervention for cognitive deficits in Alzheimer's dementia: A randomized controlled trial.

Background: Recent disease-modifying treatments for Alzheimer's disease show promise to slow cognitive decline, but show no efficacy towards reducing symptoms already manifested.

Objectives: To investigate the efficacy of a novel noninvasive brain stimulation technique in modulating cognitive functioning in Alzheimer's dementia (AD).

Design: Pilot, randomized, double-blind, parallel, sham-controlled study SETTING: Clinical research site at UT Southwestern Medical Center PARTICIPANTS: Twenty-five participants with clinical diagnoses of AD were enrolled from cognition specialty clinics.

Metabolic profiles of cutaneous lupus have abnormalities in the nicotinamide adenine dinucleotide pathway.

Objective: Metabolic reprogramming plays a critical role in modulating the innate and adaptive immune response, but its role in cutaneous autoimmune diseases, such as cutaneous lupus erythematosus (CLE), is less well studied. An improved understanding of the metabolic pathways dysregulated in CLE may lead to novel treatment options, biomarkers and insights into disease pathogenesis. The objective was to compare metabolomic profiles in the skin and sera of CLE and control patients using liquid chromatography-mass spectrometry (LC-MS).

Urine proteomics defines an immune checkpoint-associated nephritis signature.

Immune checkpoint inhibitor (ICI) therapy is a cornerstone treatment for many cancers, but it can induce severe immunotoxicity, including acute interstitial nephritis (AIN). Currently, kidney biopsy is required to differentiate ICI-AIN from other causes of acute kidney injury (AKI). However, this invasive approach can lead to morbidity, delayed glucocorticoid treatment for patients with AIN, and unnecessarily prolonged suspension of ICI therapy in non-AIN patients.

Arterial Stiffness and Subsequent Incidence of CKD and Kidney Function Decline in a Large Longitudinal Community Cohort: The Atherosclerosis in Communities (ARIC) Study.

Rationale & Objective: Arterial stiffness is associated with prevalent chronic kidney disease (CKD). Whether arterial stiffness is prospectively associated with incident CKD is inconclusive.

Study Design: Longitudinal cohort study.

Semantic Memory Space Becomes Denser with Age.

Semantic memory, a repository for concepts and factual information, plays a vital role in acquiring and retrieving knowledge. This study explores the impact of age-related knowledge accumulation on semantic cognition, investigating whether a denser representational space affects retrieval processes. Using a semantic feature verification task, we employ both behavioral (reaction time; RT) and neurophysiological (event-related potential; ERP) measures to explore these dynamics across young and older adults.

Contemporary Approach to the Diagnosis and Classification of Intestinal T-cell Lymphomas.

We provide an overview of recent advances in the diagnosis and classification of intestinal T- and NK-cell lymphomas and lymphoproliferative disorders that primarily involve the gastrointestinal (GI) tract. It should be mentioned that systemic T- and NK-cell lymphomas can present initially in the GI tract but are not the focus of this review. Here, we focus on the clinical and pathologic findings of enteropathy-associated T-cell lymphoma, monomorphic epitheliotropic intestinal T-cell lymphoma, intestinal T-cell lymphoma not otherwise specified, indolent T-cell lymphoproliferative disorder of the GI tract and indolent NK-cell lymphoproliferative disorder of the GI tract (previously known as NK-cell enteropathy).

Discordance in acute gastrointestinal toxicity between synchrotron-based proton and linac-based electron ultra-high dose rate irradiation.

Purpose: Proton FLASH has been investigated using cyclotron and synchrocyclotron beamlines but not synchrotron beamlines. We evaluated the impact of dose rate (ultra-high [UHDR] vs. conventional [CONV]) and beam configuration (shoot-through [ST] vs.

Structures and mRNP remodeling mechanism of the TREX-2 complex.

mRNAs are packaged with proteins into messenger ribonucleoprotein complexes (mRNPs) in the nucleus. mRNP assembly and export are of fundamental importance for all eukaryotic gene expression. Before export to the cytoplasm, mRNPs undergo dynamic remodeling governed by the DEAD-box helicase DDX39B (yeast Sub2).

Immunology of Biliary Atresia.

Biliary atresia is a progressive neonatal cholangiopathy that leads to liver failure. Characterized by inflammation-mediated liver injury, the immune system plays a critical role in the pathogenesis of this disease. Though several types of immune cells and mediators have been implicated in animal models of biliary atresia, emerging literature reflects the complex interplay of components of the immune response that contributes to disease progression in humans.

Influence of prosthetic foot selection on walking performance during various load carriage conditions.

Background: Ambulatory individuals with lower limb amputations often face challenges with body support, body propulsion, and balance control. Carrying an infant, toddler, backpack, or other load can exacerbate these challenges and highlights the importance of prescribing the most suitable prosthetic foot. The aim of this study was to examine the influence of five different prosthetic feet on walking performance during various load carriage conditions.

Binding a C-appended rhenium-(Bispyridine) carbonyl complex to β-Lactoglobulin: Effects of pH & cysteine modification on calyx affinity.

Due to its commercial availability and well-defined structure, the interaction between bovine protein β-lactoglobulin (βLG) and a wide variety of non-native ligands - including transition metal complexes - has been explored, but its application as an artificial metalloenzyme scaffold is limited. This protein is hypothesized to transport fatty acids and other nutrients during juvenile development, and it binds hydrophobic ligands inside a binding pocket constructed upon an 8-stranded β-barrel, called the 'calyx'. Herein, we compare the binding behavior of two rhenium(anthracene-bispyridine) ('Anth-py') tricarbonyl complexes, one with a 12‑carbon chain appended to the ligand scaffold ('Anth-py') to βLG.

HemaScope: A Tool for Analyzing Single-cell and Spatial Transcriptomics Data of Hematopoietic Cells.

Single-cell RNA sequencing (scRNA-seq) and spatial transcriptomics (ST) techniques hold great value in evaluating the heterogeneity and spatial characteristics of hematopoietic cells within tissues. These two techniques are highly complementary, with scRNA-seq offering single-cell resolution and ST retaining spatial information. However, there is an urgent demand for well-organized and user-friendly toolkits capable of handling single-cell and spatial information.

Adjuvant radiation therapy improves outcome of patients with surgical resected adrenocortical carcinoma.

Purpose: Adrenocortical carcinoma (ACC) is a rare malignancy known for high rates of recurrence and poor prognosis. Previous studies revealed controversial roles of adjuvant radiation therapy (RT) in patient management. This study aimed to investigate the role of adjuvant RT in postoperative ACC patients.

Coarse-Graining Chemical Networks by Trimming to Preserve Energy Dissipation.

Continuous production of entropy and the corresponding energy dissipation is a defining characteristic of nonequilibrium systems. When a system's full chemical kinetic description is known, its entropy production rate can be computed from the microscopic rate constants. However, such a calculation typically underestimates energy dissipation when the states of the underlying system are mesoscopic, i.

EPR Characterization of the BlsE Substrate Radical Offers Insight into the Determinants of Reaction Outcome that Distinguish Radical SAM Dioldehydratases from Dehydrogenases.

A small but growing set of radical SAM (-adenosyl-l-methionine) enzymes catalyze the radical mediated dehydration or dehydrogenation of 1,2-diol substrates. In some cases, these activities can be interchanged via minor structural perturbations to the reacting components raising questions regarding the relative importance of hyperconjugation, proton circulation and leaving group stability in determining the reaction outcome. The present work describes trapping and electron paramagnetic resonance (EPR) characterization of an α-hydroxyalkyl radical intermediate during dehydration and dehydrogenation of cytosylglucuronic acid and its derivatives catalyzed by the radical SAM enzyme BlsE and its Glu189Ala mutant from the blasticidin S biosynthetic pathway.

Contribution of Nuclear Fragmentation to Dose and RBE in Carbon-Ion Radiotherapy.

Variable relative biological effectiveness (RBE) of carbon radiotherapy may be calculated using several models, including the microdosimetric kinetic model (MKM), stochastic MKM (SMKM), repair-misrepair-fixation (RMF) model, and local effect model I (LEM), which have not been thoroughly compared. In this work, we compared how these four models handle carbon beam fragmentation, providing insight into where model differences arise. Monoenergetic and spread-out Bragg peak carbon beams incident on a water phantom were simulated using Monte Carlo.