LIN28B-mediated PI3K/AKT pathway activation promotes metastasis in colorectal cancer models.

Colorectal cancer (CRC) remains a leading cause of cancer death due to metastatic spread. LIN28B is overexpressed in 30% of CRCs and promotes metastasis, yet its mechanisms remain unclear. In this study, we genetically modified CRC cell lines to overexpress LIN28B, resulting in enhanced PI3K/AKT pathway activation and liver metastasis in mice.

A Proposed mHealth Intervention to Address Patient Barriers to Colposcopy Attendance: Qualitative Interview Study of Clinic Staff and Patient Perspectives.

Background: Cervical cancer disparities persist among minoritized women due to infrequent screening and poor follow-up. Structural and psychosocial barriers to following up with colposcopy are problematic for minoritized women. Evidence-based interventions using patient navigation and tailored telephone counseling, including the Tailored Communication for Cervical Cancer Risk (TC3), have modestly improved colposcopy attendance.

Analogue-Sensitive Inhibition of Histone Demethylases Uncovers Member-Specific Function in Ribosomal Protein Synthesis.

Lysine demethylases (KDMs) catalyze the oxidative removal of the methyl group from histones using earth-abundant iron and the metabolite 2-oxoglutarate (2OG). KDMs have emerged as master regulators of eukaryotic gene expression and are novel drug targets; small-molecule inhibitors of KDMs are in the clinical pipeline for the treatment of human cancer. Yet, mechanistic insights into the functional heterogeneity of human KDMs are limited, necessitating the development of chemical probes for precision targeting.

Use of the Ostial Flash balloon in aorto-ostial chronic total occlusion percutaneous coronary intervention.

Background: The use of the Ostial Flash balloon (Ostial Corporation) has received limited study in aorto-ostial chronic total occlusion (CTO) percutaneous coronary artery intervention (PCI).

Methods: The authors evaluated the outcomes of Ostial Flash balloon use in a large CTO-PCI registry (PROGRESS-CTO, NCT02061436).

Results: The Ostial Flash balloon was used in 54 of 907 aorto-ostial CTO PCIs in 905 patients (6.

Timing of neuroprognostication in the ICU.

Purpose Of Review: Neuroprognostication after acute brain injury (ABI) is complex. In this review, we examine the threats to accurate neuroprognostication, discuss strategies to mitigate the self-fulfilling prophecy, and how to approach the indeterminate prognosis.

Recent Findings: The goal of neuroprognostication is to provide a timely and accurate prediction of a patient's neurologic outcome so treatment can proceed in accordance with a patient's values and preferences.

Screening for Osteoporosis to Prevent Fractures: A Systematic Evidence Review for the US Preventive Services Task Force.

Importance: Fragility fractures result in significant morbidity.

Objective: To review evidence on osteoporosis screening to inform the US Preventive Services Task Force.

Data Sources: PubMed, Embase, Cochrane Library, and trial registries through January 9, 2024; references, experts, and literature surveillance through July 31, 2024.

Knowledge and Use of Menthol-Mimicking Cigarettes Among Adults in the US.

Importance: Cigarette companies have been introducing synthetic cooling agent menthol-mimicking cigarettes into the US marketplace as menthol cigarette bans are implemented. These cigarettes may reduce the public health benefits of menthol cigarette bans.

Objective: To examine the epidemiology of the use of synthetic cooling agent menthol-mimicking cigarettes among adults in the US.

Formulation of Quality Improvement Methodology for Risk Mitigation in Congenital Cardiac Catheterization.

The C3PO collaborative, with a history of successful quality improvement (QI) initiatives, leveraged registry participants to develop a multi-center QI initiative to reduce adverse events (AEs) in congenital cardiac catheterization. A 32-person, interdisciplinary working group analyzed audited data for all congenital cardiac catheterization cases from 2014-2017. The primary outcome was the occurrence of any high-severity (level 3/4/5) AE.

Cu-Ni Oxidation Mechanism Unveiled: A Machine Learning-Accelerated First-Principles and TEM Study.

The development of accurate methods for determining how alloy surfaces spontaneously restructure under reactive and corrosive environments is a key, long-standing, grand challenge in materials science. Using machine learning-accelerated density functional theory and rare-event methods, in conjunction with environmental transmission electron microscopy (ETEM), we examine the interplay between surface reconstructions and preferential segregation tendencies of CuNi(100) surfaces under oxidation conditions. Our modeling approach predicts that oxygen-induced Ni segregation in CuNi alloys favors Cu(100)-O c(2 × 2) reconstruction and destabilizes the Cu(100)-O (2√2 × √2)45° missing row reconstruction (MRR).

Evolutionary Pressures Shape Undifferentiated Pleomorphic Sarcoma Development and Radiotherapy Response.

Radiotherapy is an integral component in the treatment of many types of cancer, with approximately half of cancer patients receiving radiotherapy. Systemic therapy applies pressure that can select for resistant tumor subpopulations, underscoring the importance of understanding how radiation impacts tumor evolution to improve treatment outcomes. We integrated temporal genomic profiling of 120 spatially distinct tumor regions from 20 patients with undifferentiated pleomorphic sarcomas (UPS), longitudinal circulating tumor DNA (ctDNA) analysis, and evolutionary biology computational pipelines to study UPS evolution during tumorigenesis and in response to radiotherapy.

QOT: Quantized Optimal Transport for sample-level distance matrix in single-cell omics.

Single-cell technologies have enabled the high-dimensional characterization of cell populations at an unprecedented scale. The innate complexity and increasing volume of data pose significant computational and analytical challenges, especially in comparative studies delineating cellular architectures across various biological conditions (i.e.

Phase I Dose Volume Escalation of Rectally Administered PC-1005 to Assess Safety, Pharmacokinetics, and Antiviral Pharmacodynamics as a Multipurpose Prevention Technology (MTN-037).

Background: On demand, topical PrEP is desired by those preferring episodic, nonsystemic PrEP. PC-1005 gel (MIV-150, zinc, and carrageenan) exhibits in vitro antiviral HIV-1, human papillomavirus (HPV), and herpes simplex virus type 2 (HSV-2) activity, attractive for a multipurpose prevention technology candidate. We evaluated the safety, pharmacokinetics, and antiviral effect of rectally applied PC-1005.

Two-stage photodegradation of indomethacin molecular nanocomposites under extreme confinement.

The incorporation of a glassy material into a self-assembled nanoparticle (NP) film can produce highly loaded nanocomposites. Reduction of the NP diameter can lead to extreme nanoconfinement of the glass, significantly affecting the thermal and physical properties of the nanocomposite material. Here, we investigate the photostability and photodegradation mechanisms of molecular nanocomposite films (MNCFs) produced from the infiltration of indomethacin (IMC) molecules into self-assembled films of silica NPs (11-100 nm in diameter).

Accurate machine learning of rate coefficients for state-to-state transitions in molecular collisions.

We present an algorithm that combines quantum scattering calculations with probabilistic machine-learning models to predict quantum dynamics rate coefficients for a large number of state-to-state transitions in molecule-molecule collisions much faster than with direct solutions of the Schrödinger equation. By utilizing the predictive power of Gaussian process regression with kernels, optimized to make accurate predictions outside of the input parameter space, the present strategy reduces the computational cost by about 75%, with an accuracy within 5%. Our method uses temperature dependences of rate coefficients for transitions from the isolated states of initial rotational angular momentum j, determined via explicit calculations, to predict the temperature dependences of rate coefficients for other values of j.

Surgical Opioid Stewardship: From the Epidemic Through the Pandemic and Beyond.

Background: In response to the opioid epidemic, prescribing guidelines and statewide surgical opioid management programs were initiated in 2018-19. This analysis aims to document the sustainability of a regional opioid stewardship consortium through the pandemic and beyond.

Study Design: From September 2019 through August 2023, 15 NSQIP hospitals in two states gathered opioid-specific variables on patients undergoing 12 procedures.

Lyme neuroborreliosis in Japan: Borrelia burgdorferi sensu lato as a cause of meningitis of previously undetermined etiology in hospitalized patients outside of the island of Hokkaido, 2010-2021.

Background And Purpose: Clinical manifestations of Lyme borreliosis (LB), caused by Borrelia burgdorferi sensu lato (Bbsl), include erythema migrans, Lyme neuroborreliosis (LNB), carditis, and arthritis. LB is a notifiable disease in Japan with <30 surveillance-reported LB cases annually, predominately from Hokkaido Prefecture. However, LB, including LNB, may be under-diagnosed in Japan since diagnostic tests are not readily available.

Clinical criteria for limbic-predominant age-related TDP-43 encephalopathy.

Limbic predominant age-related TDP-43 encephalopathy neuropathologic change (LATE-NC) is highly prevalent in late life and a common co-pathology with Alzheimer's disease neuropathologic change (ADNC). LATE-NC is a slowly progressive, amnestic clinical syndrome. Alternatively, when present with ADNC, LATE-NC is associated with a more rapid course.

Imidazolium-Based Ionic Liquid Exhibiting Dual Hydrophilic and Oleophobic Properties without Polar End Groups.

Simultaneously hydrophilic and oleophobic surfaces offer substantial advantages for applications such as antifogging, self-cleaning, and oil-water separation. It remains challenging to engineer such surfaces without requiring polar functional groups. This study introduces HFIL, a novel ionic liquid (IL) coating that achieves simultaneous hydrophilic and oleophobic properties via a one-step dip-coating process without relying on polar functional groups.

Longitudinal Outcomes in Noonan Syndrome.

Purpose: Noonan syndrome and related disorders (NS) are multisystemic conditions affecting approximately 1:1000 individuals. Previous natural history studies were conducted prior to widespread comprehensive genetic testing. This study provides updated longitudinal natural history data in participants with molecularly confirmed NS.

Decoding brain structure to stage Alzheimer's disease pathology in Down syndrome.

Introduction: Alzheimer's disease (AD) in Down syndrome (DS) is associated with changes in brain structure. It is unknown if thickness and volumetric changes can identify AD stages and if they are similar to other genetic forms of AD.

Methods: Magnetic resonance imaging scans were collected for 178 DS adults (106 nonclinical, 45 preclinical, and 27 symptomatic).