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.

Increasing the acquisition speed in oblique plane microscopy via Aliasing.

Oblique plane microcopy (OPM), a variant of light-sheet fluorescence microscopy (LSFM), enables rapid volumetric imaging without mechanically scanning the sample or an objective. In an OPM, the sample space is mapped to a distortion free image space via remote focusing, and the oblique light-sheet plane is mapped via a tilted tertiary imaging system onto a camera. As a result, the 3D point-spread function and optical transfer function are tilted to the optical axis of the tertiary imaging system.

Genetically Labeled Premyelinating Oligodendrocytes: Bridging Oligodendrogenesis and Neuronal Activity.

To myelinate axons, oligodendrocyte precursor cells (OPCs) must stop dividing and differentiate into premyelinating oligodendrocytes (preOLs). PreOLs are thought to survey and begin ensheathing nearby axons, and their maturation is often stalled at human demyelinating lesions. Lack of genetic tools to visualize and manipulate preOLs has left this critical differentiation stage woefully understudied.

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.

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.

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.

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.

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.

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.

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.

Sensory quiescence induces a cell-non-autonomous integrated stress response curbed by condensate formation of the ATF4 and XRP1 effectors.

Sensory disabilities have been identified as significant risk factors for dementia but underlying molecular mechanisms are unknown. In different Drosophila models with loss of sensory input, we observe non-autonomous induction of the integrated stress response (ISR) deep in the brain, as indicated by eIF2α phosphorylation-dependent elevated levels of the ISR effectors ATF4 and XRP1. Unlike during canonical ISR, however, the ATF4 and XRP1 transcription factors are enriched in cytosolic granules that are positive for RNA and the stress granule markers Caprin, FMR1, and p62, and are reversible upon restoration of vision for blind flies.

The revised colorectal cancer screening guideline and screening burden at community health centers.

Colorectal cancer (CRC) is the third most common cancer among men and women combined, and the second leading cause of cancer death in the US. The revised USPSTF CRC screening recommendations increased CRC screening needs across health systems, which may create particular challenges for community health centers (CHCs) given their resource constraints. The objective of our study is to assess CRC screening rates across 10 CHCs in Massachusetts and estimate the additional increase in the number of average-risk screening-eligible individuals after the revision in guidelines.

Real-time CBCT imaging and motion tracking via a single arbitrarily-angled x-ray projection by a joint dynamic reconstruction and motion estimation (DREME) framework.

Real-time cone-beam computed tomography (CBCT) provides instantaneous visualization of patient anatomy for image guidance, motion tracking, and online treatment adaptation in radiotherapy. While many real-time imaging and motion tracking methods leveraged patient-specific prior information to alleviate under-sampling challenges and meet the temporal constraint (< 500 ms), the prior information can be outdated and introduce biases, thus compromising the imaging and motion tracking accuracy. To address this challenge, we developed a framework (DREME) for real-time CBCT imaging and motion estimation, without relying on patient-specific prior knowledge.

Tumor immunomodulation by nanoparticle and focused ultrasound alters gut microbiome in a sexually dimorphic manner.

Local immunomodulation with nanoparticles (NPs) and focused ultrasound (FUS) is recognized for triggering anti-tumor immunity. However, the impact of these tumor immunomodulations on sex-specific microbiome diversity at distant sites and their correlation with therapeutic effectiveness remains unknown. Here, we conducted local intratumoral therapy using immunogenic cell death-enhancing Calreticulin-Nanoparticles (CRT-NPs) and FUS in male and female mice.

Retrograde approach to chronic total occlusion percutaneous coronary interventions- Technique and outcomes.

The retrograde approach to chronic total occlusion (CTO) percutaneous coronary intervention (PCI) has significantly contributed to the success rates of CTO PCI. It is usually performed in complex CTO lesions, in which the antegrade approach is not feasible or fails. In this article we discuss the steps to perform retrograde CTO PCI and its complications and success rates.

MRI-derived radiomics and end-to-end deep learning models for predicting glioma ATRX status: a systematic review and meta-analysis of diagnostic test accuracy studies.

We aimed to systematically review and meta-analyze the predictive value of magnetic resonance imaging (MRI)-derived radiomics/end-to-end deep learning (DL) models in predicting glioma alpha thalassemia/mental retardation syndrome X-linked (ATRX) status. We conducted a comprehensive search across four major databases-Web of Science, PubMed, Scopus, and Embase. All the studies that assessed the performance of radiomics and/or end-to-end DL models for predicting glioma ATRX status were included.