Pulsed Field Ablation in the Elderly via a Pentaspline Multielectrode Catheter: Safety, Efficacy, and Comparison with Cryoballoon and Radiofrequency Devices.

Background: Catheter ablation is an effective treatment for atrial fibrillation (AF). Pulsed field ablation (PFA) has emerged as a novel energy modality, which relies on high-voltage electric fields to achieve cardiac tissue ablation. Data on its efficacy in the elderly are scarce.

Cytoplasmic expression of trans-active response DNA-binding protein-43 in aged mice display hippocampal sclerosis-like degeneration and neuronal loss with reduced lifespan.

Trans-active response DNA-binding protein-43 (TDP-43) is the major pathological protein in motor neuron disease and TDP-43 pathology has been described in the brains of up to 50% of patients with Alzheimer disease (AD). Hippocampal sclerosis of aging (HS-A), an age-related neuropathology characterized by severe neuronal loss and gliosis in CA1 and/or subiculum, is found in ∼80% of cases that are positive for phosphorylated TDP-43. HS-A is seen as a co-pathology in cases with AD, limbic-predominant age-related TDP-43 encephalopathy neuropathologic changes (LATE-NC), and frontotemporal degeneration.

Characterizing the relationship between personality dimensions and psychosis-specific clinical characteristics.

Background: Past studies associating personality with psychosis have been limited by small nonclinical samples and a focus on general symptom burden. This study uses a large clinical sample to examine personality's relationship with psychosis-specific features and compare personality dimensions across clinically and neurobiologically defined categories of psychoses.

Methods: A total of 1352 participants with schizophrenia, schizoaffective disorder, and bipolar with psychosis, as well as 623 healthy controls (HC), drawn from the Bipolar-Schizophrenia Network for Intermediate Phenotypes (BSNIP-2) study, were included.

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.

A Comprehensive Atlas of AAV Tropism in the Mouse.

Gene therapy with Adeno-Associated Virus (AAV) vectors requires knowledge of their tropism within the body. Here we analyze the tropism of ten naturally occurring AAV serotypes (AAV3B, AAV4, AAV5, AAV6, AAV7, AAV8, AAV9, AAVrh8, AAVrh10 and AAVrh74) following systemic delivery into male and female mice. A transgene expressing ZsGreen and Cre recombinase was used to identify transduction in a cell-dependent manner based on fluorescence.

Global metabolomic alterations associated with endocrine-disrupting chemicals among pregnant individuals and newborns.

Background: Gestational exposure to non-persistent endocrine-disrupting chemicals (EDCs) may be associated with adverse pregnancy outcomes. While many EDCs affect the endocrine system, their effects on endocrine-related metabolic pathways remain unclear. This study aims to explore the global metabolome changes associated with EDC biomarkers at delivery.

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.

Multidimensional library for the improved identification of per- and polyfluoroalkyl substances (PFAS).

As the occurrence of human diseases and conditions increase, questions continue to arise about their linkages to chemical exposure, especially for per-and polyfluoroalkyl substances (PFAS). Currently, many chemicals of concern have limited experimental information available for their use in analytical assessments. Here, we aim to increase this knowledge by providing the scientific community with multidimensional characteristics for 175 PFAS and their resulting 281 ion types.

The 40S ribosomal subunit recycling complex modulates mitochondrial dynamics and endoplasmic reticulum - mitochondria tethering at mitochondrial fission/fusion hotspots.

The 40S ribosomal subunit recycling pathway is an integral link in the cellular quality control network, occurring after translational errors have been corrected by the ribosome-associated quality control (RQC) machinery. Despite our understanding of its role, the impact of translation quality control on cellular metabolism remains poorly understood. Here, we reveal a conserved role of the 40S ribosomal subunit recycling (USP10-G3BP1) complex in regulating mitochondrial dynamics and function.

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.

Maternal and neonatal outcomes after metabolic and bariatric surgery among women with severe obesity.

Background: Earlier evidence indicated that metabolic and bariatric surgery (MBS) may adversely affect neonatal outcomes among patients conceiving soon after MBS, but recent studies demonstrated conflicting results, especially for new surgical techniques.

Objectives: The aim of this study was to assess the effects of MBS types and surgery to birth interval on maternal, birth, and nonbirth outcomes in women with severe obesity.

Setting: New York State's all-payer hospital discharge database (2008-2019).

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.

AGA Clinical Practice Guideline on the Prevention and Treatment of Hepatitis B Virus Reactivation in At-Risk Individuals.

Background & Aims: Hepatitis B reactivation (HBVr) can occur due to a variety of immune-modulating exposures, including multiple drug classes and disease states. Antiviral prophylaxis can be effective in mitigating the risk of HBVr. In select cases, clinical monitoring without antiviral prophylaxis is sufficient for managing the risk of HBVr.

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.

Novel B7-H3 CAR T cells show potent antitumor effects in glioblastoma: a preclinical study.

Background: B7 homolog 3 (B7-H3), an overexpressed antigen across multiple solid cancers, represents a promising target for CAR T cell therapy. This study investigated the expression of B7-H3 across various solid tumors and developed novel monoclonal antibodies (mAbs) targeting B7-H3 for CAR T cell therapy.

Methods: Expression of B7-H3 across various solid tumors was evaluated using RNA-seq data from TCGA, TARGET, and GTEx datasets and by flow cytometry staining.

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.

The biological intersection between chemotherapy-related cognitive impairment and Alzheimer's disease.

Alzheimer's disease (AD) is the most common type of dementia and one of the leading causes of death in elderly patients. The number of patients with AD in the United States is projected to double by 2060. Thus, understanding modifiable risk factors for AD is an urgent public health priority.

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.