Genomic and Transcriptomic Profiling of Digital Papillary Adenocarcinomas Reveals Alterations in Matrix Remodeling and Metabolic Genes.

Background: Digital papillary adenocarcinoma (DPAC) is a rare but aggressive cutaneous malignant sweat gland neoplasm that occurs on acral sites. Despite its clinical significance, the cellular and genetic characteristics of DPAC remain incompletely understood.

Methods: We conducted a comprehensive genomic and transcriptomic analysis of DPAC (n = 14) using targeted next-generation DNA and RNA sequencing, along with gene expression profiling employing the Nanostring Technologies nCounter IO 360 Panel.

A Simple Endoscopic Score for Crohn's Disease (SES-CD) ≥ 7 Predicts Disease Progression.

Background: Up to 30% of patients with Crohn's disease (CD) will experience a mild disease course. However, there is no consensus definition for mild CD.

Aim: To examine the Simple Endoscopic Score for Crohn's disease (SES-CD) thresholds best associated with low likelihood of long-term disease progression.

Characterizing populations prioritized for PrEP in 19 African countries: a review of national guidance.

Introduction: While African countries have expanded access to HIV pre-exposure prophylaxis (PrEP) since 2015, regional targets for PrEP uptake remain unmet. Understanding which populations are prioritized for PrEP at the policy level is an important step in determining the scope of PrEP distribution across Africa and identifying gaps in programme implementation. We reviewed national guidance to characterize populations prioritized for PrEP in Africa.

Development of Receptor Desolvation Scoring and Covalent Sampling in DOCK 6: Methods Evaluated on a RAS Test Set.

Molecular docking methods are widely used in drug discovery efforts. RAS proteins are important cancer drug targets, and are useful systems for evaluating docking methods, including accounting for solvation effects and covalent small molecule binding. Water often plays a key role in small molecule binding to RAS proteins, and many inhibitors─including FDA-approved drugs─covalently bind to oncogenic RAS proteins.

Prenatal polycyclic aromatic hydrocarbons exposure and child growth and adiposity: A longitudinal study.

Background: Exposure to polycyclic aromatic hydrocarbons (PAHs) during childhood has been associated with altered growth and adiposity in children. The effects of prenatal exposure to PAHs on developmental programming of growth and adiposity are still unknown.

Objective: To study the association of prenatal exposure to PAHs with early childhood growth and adiposity measures.

Development of the retinoic acid receptor alpha-specific antagonist YCT-529 for male contraception: A brief review.

Genetic studies in mice have demonstrated that retinoic acid receptor alpha (RARα) deficiency leads to male infertility without affecting overall viability, suggesting that pharmacological inhibition of this receptor could be a viable contraceptive strategy. This review describes the use of experimental approaches to develop RARα-selective antagonists for male contraception. Initial studies with BMS-189453, a pan-RAR antagonist, showed significant testicular degeneration and reversible infertility in mice.

Pulmonary neuroendocrine neoplasms: the molecular landscape, therapeutic challenges, and diagnosis and management strategies.

Lung neuroendocrine neoplasms are a group of diverse, heterogeneous tumours that range from well-differentiated, low-grade neuroendocrine tumours-such as typical and atypical carcinoids-to high-grade, poorly differentiated aggressive malignancies, such as large-cell neuroendocrine carcinoma (LCNEC) and small-cell lung cancer (SCLC). While the incidence of SCLC has decreased, the worldwide incidence of other pulmonary neuroendocrine neoplasms has been increasing over the past decades. In addition to the standard histopathological classification of lung neuroendocrine neoplasms, the introduction of molecular and sequencing techniques has led to new advances in understanding the biology of these diseases and might influence future classifications and staging that can subsequently improve management guidelines in the adjuvant or metastatic settings.

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.

PFAS biodegradation by Labrys portucalensis F11: Evidence of chain shortening and identification of metabolites of PFOS, 6:2 FTS, and 5:3 FTCA.

The biodegradation of three per- and polyfluoroalkyl substances (PFAS), namely perfluorooctane sulfonic acid (PFOS), 6:2-fluorotelomer sulfonic acid (6:2 FTS), and 5:3-fluorotelomer carboxylic acid (5:3 FTCA), were evaluated using Labrys portucalensis F11, an aerobic bacteria known to defluorinate fluorine-containing compounds. Cultures of L. portucalensis F11 were grown in minimal salts media and treated with 10,000 μg/L of individual PFAS as the sole carbon source in separate flasks.

Metals in Motion: Understanding Labile Metal Pools in Bacteria.

Metal ions are essential for all life. In microbial cells, potassium (K) is the most abundant cation and plays a key role in maintaining osmotic balance. Magnesium (Mg) is the dominant divalent cation and is required for nucleic acid structure and as an enzyme cofactor.

Athlete Selective Androgen Receptor Modulators Abuse: A Systematic Review.

Background: Selective androgen receptor modulators (SARMs) are small-molecule compounds that exert agonist and antagonist effects on androgen receptors in a tissue-specific fashion. Because of their performance-enhancing implications, SARMs are increasingly abused by athletes. To date, SARMs have no Food and Drug Administration approved use, and recent case reports associate the use of SARMs with deleterious effects such as drug-induced liver injury, myocarditis, and tendon rupture.

Historical redlining and clustering of present-day breast cancer factors.

Purpose: Historical redlining, a 1930s-era form of residential segregation and proxy of structural racism, has been associated with breast cancer risk, stage, and survival, but research is lacking on how known present-day breast cancer risk factors are related to historical redlining. We aimed to describe the clustering of present-day neighborhood-level breast cancer risk factors with historical redlining and evaluate geographic patterning across the US.

Methods: This ecologic study included US neighborhoods (census tracts) with Home Owners' Loan Corporation (HOLC) grades, defined as having a score in the Historic Redlining Score dataset; 2019 Population Level Analysis and Community EStimates (PLACES) data; and 2014-2016 Environmental Justice Index (EJI) data.

Unsupervised self-organising map classification of Raman spectra from prostate cell lines uncovers substratified prostate cancer disease states.

Prostate cancer is a disease which poses an interesting clinical question: Should it be treated? Only a small subset of prostate cancers are aggressive and require removal and treatment to prevent metastatic spread. However, conventional diagnostics remain challenged to risk-stratify such patients; hence, new methods of approach to biomolecularly sub-classify the disease are needed. Here we use an unsupervised self-organising map approach to analyse live-cell Raman spectroscopy data obtained from prostate cell-lines; our aim is to exemplify this method to sub-stratify, at the single-cell-level, the cancer disease state using high-dimensional datasets with minimal preprocessing.

The public health risks of counterfeit pills.

Synthetic illicit drugs, such as nitazenes and fentanyls, are becoming commonplace in countries around the world, including in Europe, Australia, and Latin America, which raises concern for overdose crises like those seen in North America. An important dimension of the risk represented by synthetic drugs is the fact that they are increasingly packaged in counterfeit pill form. These pills-often indistinguishable from authentic pharmaceuticals-have substantially widened the scope of populations susceptible to synthetic drug overdose in North America (eg, among adolescents experimenting with pills or tourists from the USA seeking psychoactive medications from pharmacies in Mexico).

Advances in transcriptional regulation of the heart rhythm.

Underlying normal cardiac rhythm is a network of transcriptional programs that ensures normal impulse initiation and impulse propagation. We highlight work that shows how alterations in individual transcriptional networks can lead to increased arrhythmia susceptibility, cardiomyopathy, and congenital heart defects. Lastly, we focus on a study that leverages transcription factor biology to therapeutically modulate heart rhythm.

Convolutional Neural Networks for the segmentation of hippocampal structures in postmortem MRI scans.

Background: The hippocampus plays a crucial role in memory and is one of the first structures affected by Alzheimer's disease. Postmortem MRI offers a way to quantify the alterations by measuring the atrophy of the inner structures of the hippocampus. Unfortunately, the manual segmentation of hippocampal subregions required to carry out these measures is very time-consuming.

Amivantamab Plus Lazertinib in Patients With EGFR-mutant Non-small Cell Lung Cancer (NSCLC) After Progression on Osimertinib and Platinum-based Chemotherapy: Results From CHRYSALIS-2 Cohort A.

Introduction: Treatment options for patients with epidermal growth factor receptor (EGFR)-mutated non-small cell lung cancer (NSCLC) with disease progression on/after osimertinib and platinum-based chemotherapy are limited.

Methods: CHRYSALIS-2 Cohort A evaluated amivantamab+lazertinib in patients with EGFR exon 19 deletion- or L858R-mutated NSCLC with disease progression on/after osimertinib and platinum-based chemotherapy. Primary endpoint was investigator-assessed objective response rate (ORR).

Comparative species delimitation of a biological conservation icon.

The United States Endangered Species Act (ESA) of 1973 set a precedent for biodiversity conservation across the globe. A key requirement of protections afforded by the ESA is the accurate delimitation of imperiled species. We present a comparative reference-based taxonomic approach to species delimitation that integrates genomic and morphological data for objectively assessing the distinctiveness of species targeted for protection by governmental agencies.

Barriers to early detection: Insurance denials for breast MRI screening in women with germline BRCA1/2 mutations.

Objectives: Women with germline BRCA1/2 pathogenic variants (gBRCA1/2) are recommended to undergo annual breast MRI and mammography. Our objective was to describe the frequency of insurance denials for annual breast MRIs in women with gBRCA1/2 and determine denial trends.

Methods: Women with gBRCA1/2 following in a high-risk breast cancer clinic with breast MRIs ordered from 2020 to 2021 were identified and cross-referenced with a database of insurance denials.

Intraoperative FiO and risk of impaired postoperative oxygenation in lung resection: A propensity score-weighted analysis.

Study Objective: To assess whether, in a lung resection cohort with a low probability of confounding by indication, higher FiO is associated with an increased risk of impaired postoperative oxygenation - a clinical manifestation of lung injury/dysfunction.

Design: Pre-specified registry-based retrospective cohort study.

Setting: Two large academic hospitals in the United States.

Enhancing chemotherapy response prediction via matched colorectal tumor-organoid gene expression analysis and network-based biomarker selection.

Background: Colorectal cancer (CRC) presents significant challenges in chemotherapy response prediction due to its molecular heterogeneity. Current methods often fail to account for the complexity and variability inherent in individual tumors.

Methods: We developed a novel approach using matched CRC tumor and organoid gene expression data.

Coronary Intervention Outcomes in Patients with Liver Cirrhosis.

Purpose Of Review: This review assesses the outcomes of coronary interventions in patients with liver cirrhosis and coronary artery disease (CAD), focusing on the clinical challenges posed by cirrhosis-related hemodynamic and coagulopathic changes. It highlights essential considerations for managing these patients, who have an increased risk of adverse events during coronary procedures.

Recent Findings: Recent studies have shown that patients with liver cirrhosis undergoing PCI experience significantly higher mortality rates compared to non-cirrhotic patients, particularly in the context of STEMI and NSTEMI.