A Phosphatidyl Conjugated Telomerase-Dependent Telomere-Targeting Nucleoside Demonstrates Colorectal Cancer Direct Killing and Immune Signaling.

Telomerase and telomeres are crucial in cancer cell immortalization, making them key targets for anticancer therapies. Currently, 6-thio-dG (THIO) combined with the anti-PD-1 inhibitor Cemiplimab is under phase II clinical investigation (NCT05208944) in NSCLC patients resistant to prior immunotherapies. This study presents the design, synthesis, and evaluation of novel bimodular conjugate molecules combining telomere-targeting nucleoside analogs and phosphatidyl diglyceride groups.

The Proteomics of T-Cell and Early T-Cell Precursor (ETP) Acute Lymphocytic Leukemia: Prognostic Patterns in Adult and Pediatric-ETP ALL.

Background: The 5-year overall survival (OS) rates of T-cell lymphocytic leukemia (T-ALL) are better for children (>90%) compared to adults (~57%). The early T-cell precursor (ETP) T-ALL subtype is prognostically unfavorable in adults, but less significant in pediatric T-ALL, and the diagnosis and prognosis of "near"-ETP is controversial. We compared protein and RNA expression patterns in pediatric and adult T-ALL to identify prognostic subgroups, and to further characterize ETP and near-ETP T-ALL in both age groups.

Tacrolimus to belatacept conversion in proteinuric kidney transplant recipients.

Background: Proteinuria is associated with worse allograft outcomes in kidney transplant recipients (KTRs) and treatment strategies are limited. We examined the outcomes of calcineurin inhibitor (CNI) to belatacept conversion in proteinuric KTRs.

Methods: In a pilot phase II single-arm multicenter prospective trial, we recruited adult KTRs >6 months post-kidney transplantation with an estimated glomerular filtration rate (eGFR) ≥30 ml/min/1.

Novel and potent MICA/B antibody is therapeutically effective in mutant lung cancer models.

Background: Concurrent (STK11, KL) mutant non-small cell lung cancers (NSCLC) do not respond well to current immune checkpoint blockade therapies, however targeting major histocompatibility complex class I-related chain A or B (MICA/B), could pose an alternative therapeutic strategy through activation of natural killer (NK) cells.

Methods: Expression of NK cell activating ligands in NSCLC cell line and patient data were analyzed. Cell surface expression of MICA/B in NSCLC cell lines was determined through flow cytometry while ligand shedding in both patient blood and cell lines was determined through ELISA.

Association between vitamin D status at 3 years and eosinophilic asthma in 6-year-old children with a history of severe bronchiolitis.

The association between early childhood serum 25-hydroxyvitamin D (25(OH)D) and eosinophilic asthma remains unclear. We investigated this association using multicentre prospective data from 584 children with a history of bronchiolitis requiring hospitalisation (high-risk population). Low serum 25(OH)D levels (<20 ng/mL) were associated with increased odds of developing eosinophilic asthma (adjusted OR 2.

Mass Spectrometric Detection of Keratins in Tear Fluid.

Purpose: Keratin contamination is a common problem in mass spectrometry proteomic analyses, particularly in bottom-up mass spectrometry. The purpose of this study was to determine the protein contaminants introduced during the proteomic analysis of tear fluid.

Methods: Human tear fluid samples were collected using Schirmer strips.

Proton Beam Therapy for Pancreatic Tumors: A Consensus Statement from the Particle Therapy Cooperative Group Gastrointestinal Subcommittee.

Objectives: Radiotherapy manages pancreatic cancer in various settings; however, the proximity of gastrointestinal (GI) luminal organs-at-risk (OAR) poses challenges to conventional radiotherapy. Proton beam therapy (PBT) may reduce toxicities compared to photon therapy. This consensus statement summarizes PBT's safe and optimal delivery for pancreatic tumors.

Impact of psychological treatment in freezing of gait: A pilot study.

Unlabelled: One common gait issue associated with advanced Parkinson's disease (PD) is freezing of gait (FoG). FoG impacts approximately half of people with PD and negatively impacts quality of life. Studies have suggested that anxiety may contribute to FoG.

The role of MEK inhibition in pediatric low-grade gliomas.

Pediatric low-grade gliomas (pLGGs) are the most common brain tumors in children. Many patients with unresectable tumors experience recurrence or long-term sequelae from standard chemotherapeutics. This mini-review explores the emerging role of MEK inhibitors in the management of pLGGs, highlighting their potential to transform current treatment paradigms.

Changing Treatment and Metastatic Disease Patterns in Patients with EGFR Mutated NSCLC: An Academic Thoracic Medical Investigator's Consortium Registry Analysis.

Introduction: Osimertinib is now a standard first-line (1L) therapy for EGFR-mutated (EGFRm) advanced NSCLC. We aimed to characterize patterns of therapy and longitudinal risk of brain and liver metastasis in a cohort of EGFRm NSCLC.

Methods: Patients with metastatic EGFRm NSCLC who received 1L systemic therapy at sites within the Academic Thoracic Medical Investigator's Consortium were included; demographic and clinical data including treatment patterns were described.

International consensus guidelines on the implementation and monitoring of vosoritide therapy in individuals with achondroplasia.

Achondroplasia is the most common genetic form of short-limbed skeletal dysplasia (dwarfism). Clinical manifestations and complications can affect individuals across the lifespan, including the need for adaptations for activities of daily living, which can affect quality of life. Current international guidelines focus on symptomatic management, with little discussion regarding potential medication, as therapeutic options were limited at the time of their publication.

Consensus review and considerations on TMS to treat depression: A comprehensive update endorsed by the National Network of Depression Centers, the Clinical TMS Society, and the International Federation of Clinical Neurophysiology.

This article updates the prior 2018 consensus statement by the National Network of Depression Centers (NNDC) on the use of transcranial magnetic stimulation (TMS) in the treatment of depression, incorporating recent research and clinical developments. Publications on TMS and depression between September 2016 and April 2024 were identified using methods informed by PRISMA guidelines. The NNDC Neuromodulation Work Group met monthly between October 2022 and April 2024 to define important clinical topics and review pertinent literature.

BIS Guided Titration of Sevoflurane in Pediatric Patients Undergoing Elective Surgery: A Randomized Controlled Trial.

Background: In pediatric patients, the use of processed EEG monitoring may reduce the amount of anesthesia administered while maintaining adequate depth of anesthesia.

Aims: The primary aim of this study was to evaluate whether use of a BIS monitor to guide sevoflurane administration might reduce the average end tidal sevoflurane concentration used in children 4-18 years of age.

Methods: Participants in three age groups (4-8, 9-12, and 13-18 years) were randomized to either the BIS guided group or the control group.

Randomized Control Trial Evaluating Different Modalities of Real-Time Surgical Feedback.

Introduction:: Surgical training is a constant exchange between trainers and trainees, and intraoperative surgical feedback is an integral part of learning. New technologies in robotic surgery allow for the delivery of visual aid and verbal feedback intraoperatively, but it has not yet been determined if feedback type affects the trainee learning process.

Methods:: 49 novice participants were recruited and randomized into four feedback groups: , , of verbal/visual, and no feedback ().

Providing medically tailored groceries and food resource coaching through the charitable food system to patients of a safety-net clinic in Dallas, Texas: a randomised controlled trial protocol.

Introduction: Linking patients living with chronic, diet-related diseases and food insecurity to charitable food assistance, medically tailored groceries (MTGs) and food resource coaching may empower patients to better manage their health in a way that is economically sustainable. This protocol paper describes the implementation of a study evaluating MTGs and food resource coaching in a food pantry setting.

Methods And Analysis: A randomised controlled trial whereby patients of a safety-net health centre will be screened for The Emergency Food Assistance Program (TEFAP) and study eligibility.

Thalamic stereo-electroencephalography exploration in pediatric drug-resistant epilepsy: implantation technique and complications.

Objective: Patients with drug-resistant epilepsy (DRE) are often referred for phase II evaluation with stereo-electroencephalography (SEEG) to identify a seizure onset zone for guiding definitive treatment. For patients without a focal seizure onset zone, neuromodulation targeting the thalamic nuclei-specifically the centromedian nucleus, anterior nucleus of the thalamus, and pulvinar nucleus-may be considered. Currently, thalamic nuclei selection is based mainly on the location of seizure onset, without a detailed evaluation of their network involvement.

The Pelvic Floor Disorders Network: Evolution Over Two Decades of Female Pelvic Floor Research.

Importance: This review aimed to describe research initiatives, evolution, and processes of the Eunice Kennedy Shriver National Institute of Child Health and Human Development-supported Pelvic Floor Disorders Network (PFDN). This may be of interest and inform researchers wishing to conduct multisite coordinated research initiatives as well as to provide perspective to all urogynecologists regarding how the PFDN has evolved and functions.

Study Design: Principal investigators of several PFDN clinical sites and Data Coordinating Center describe more than 20 years of development and maturation of the PFDN.

Advancing precision medicine: the transformative role of artificial intelligence in immunogenomics, radiomics, and pathomics for biomarker discovery and immunotherapy optimization.

Artificial intelligence (AI) is significantly advancing precision medicine, particularly in the fields of immunogenomics, radiomics, and pathomics. In immunogenomics, AI can process vast amounts of genomic and multi-omic data to identify biomarkers associated with immunotherapy responses and disease prognosis, thus providing strong support for personalized treatments. In radiomics, AI can analyze high-dimensional features from computed tomography (CT), magnetic resonance imaging (MRI), and positron emission tomography/computed tomography (PET/CT) images to discover imaging biomarkers associated with tumor heterogeneity, treatment response, and disease progression, thereby enabling non-invasive, real-time assessments for personalized therapy.

Post-acute sequela of COVID-19 infection in individuals with multiple sclerosis.

Background: Many common symptoms in post-acute sequelae following severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection (PASC) overlap with those of multiple sclerosis (MS). We examined symptoms and performance of the PASC score, developed in the general population, in MS based on infection history.

Methods: We surveyed North American Research Committee on Multiple Sclerosis (NARCOMS) registry participants regarding infections and categorized participants based on infection history.

Prostatic E. coli infection drives CCR2-dependent recruitment of fibrocytes and collagen production.

Prostate fibrosis contributes to lower urinary tract dysfunction (LUTD). To develop targeted treatments for prostate fibrosis, it is necessary to identify cell types and molecular pathways required for collagen production. We used a genetic approach to label and track potential collagen-producing cell lineages in mouse prostate through a round of Escherichia coli (E.