Regulation of metastatic organotropism.

Metastasis is responsible for most cancer-related deaths. Different cancers have their own preferential sites of metastases, a phenomenon termed metastatic organotropism. The mechanisms underlying organotropism are multifactorial and include the generation of a pre-metastatic niche (PMN), metastatic homing, colonization, dormancy, and metastatic outgrowth.

A Crisis in Scope: Recruitment and Retention Challenges Reported by VA Gastroenterology Section Chiefs.

Background: Having a sufficient number of gastroenterologists is important for protecting the digestive health of veterans. However, gastroenterology is among the most difficult medical specialties for recruitment at the US Department of Veterans Affairs (VA).

Methods: We surveyed VA gastroenterology section chiefs to learn about current barriers to recruitment and retention and to identify opportunities for improvement.

Virtual Reality Videos for Symptom Management in Hospice and Palliative Care.

Objective: To learn more about the effect of virtual reality videos on patients' symptoms near the end of life, including which are most effective, how long the effect lasts, and which patients benefit the most.

Patients And Methods: We conducted a prospective study of 30 patients in a regional hospice and palliative care program from March 11, 2022, through July 14, 2023. Using a head-mounted display virtual reality, all participants viewed a 15-minute video of serene nature scenes with ambient sounds.

Lactate Suppresses Growth of Esophageal Adenocarcinoma Patient-Derived Organoids through Alterations in Tumor NADH/NAD+ Redox State.

Barrett's esophagus (BE) is a common precancerous lesion that can progress to esophageal adenocarcinoma (EAC). There are significant alterations in the esophageal microbiome in the progression from healthy esophagus to BE to EAC, including an increased abundance of a variety of lactate-producing bacteria and an increase of lactate in the tumor microenvironment, as predicted by metabolic modeling. The role of bacterial lactate in EAC is unknown.

An Enzymatic Prodrug-like Route to Thio and Selenoamides.

6-Thioguanine (6TG) is a clinically used antitumor agent that was rationally designed as a DNA-targeting antimetabolite, but it also occurs naturally. 6TG is a critical virulence factor produced by Erwinia amylovorans, a notorious plant pathogen that causes fire blight of pome fruit trees. The biosynthesis of the rare thioamide metabolite involves an adenylating enzyme (YcfA) and a sulfur-mobilizing enzyme (YcfC), but the mechanism of sulfur transfer and putative intermediates have remained elusive.

Tumor niche network-defined subtypes predict immunotherapy response of esophageal squamous cell cancer.

Despite the promising outcomes of immune checkpoint inhibitors (ICIs), resistance to ICI presents a new challenge. Therefore, selecting patients for specific ICI applications is crucial for maximizing therapeutic efficacy. Herein, we curated 69 human esophageal squamous cell cancer (ESCC) patients' tumor microenvironment (TME) single-cell transcriptomic datasets to subtype ESCC.

Hypoxia-inducible factor-1α mediates reflux-induced epithelial-mesenchymal plasticity in Barrett's oesophagus patients.

Introduction: Epithelial-mesenchymal plasticity (EMP), the process through which epithelial cells acquire mesenchymal features, is needed for wound repair but also might contribute to cancer initiation. Earlier, in vitro studies showed that Barrett's cells exposed to acidic bile salt solutions (ABS) develop EMP. Now, we have (1) induced reflux oesophagitis in Barrett's oesophagus (BO) patients by stopping proton pump inhibitors (PPIs), (2) assessed their biopsies for EMP and (3) explored molecular pathways underlying reflux-induced EMP in BO cells and spheroids.

Phage-specific immunity impairs efficacy of bacteriophage targeting Vancomycin Resistant Enterococcus in a murine model.

Bacteriophage therapy is a promising approach to address antimicrobial infections though questions remain regarding the impact of the immune response on clinical effectiveness. Here, we develop a mouse model to assess phage treatment using a cocktail of five phages from the Myoviridae and Siphoviridae families that target Vancomycin-Resistant Enterococcus gut colonization. Phage treatment significantly reduces fecal bacterial loads of Vancomycin-Resistant Enterococcus.

Cancer-Associated Fibroblasts in Esophageal Cancer.

Cancer-associated fibroblasts (CAFs), a heterogenous population, can promote cancer cell proliferation, migration, invasion, immunosuppression, and therapeutic resistance in solid tumors. These effects are mediated through secretion of cytokines and growth factors, remodeling of the extracellular matrix, and providing metabolic support for cancer cells. The presence of CAFs in esophageal carcinoma are associated with reduced overall survival and increased resistance to chemotherapy and radiotherapy; thus, identifying therapeutic vulnerabilities of CAFs is a necessity.

When to Transfer: Predictors of Pediatric High Flow Nasal Cannula Failure at a Community Hospital.

Objectives: To identify risk factors of high flow nasal cannula (HFNC) failure at a US pediatric hospital without a co-located ICU.

Methods: Retrospective cohort study of patients aged 0 to 18 years who were started on HFNC in the emergency department or inpatient unit at a community hospital over a 16-month period. Children with chronic medical conditions were excluded.

utilizes siderophores as an iron source and FhuDBGC contributes to ferrichrome uptake.

This study is the first example of growing with siderophores as the sole iron source and describes the characterization of the ferric hydroxamate uptake ABC transporter (FhuDBGC). This transporter shows specificity to the siderophore ferrichrome. While not required for pathogenesis, this transporter highlights the redundancy in iron acquisition mechanisms that uses to compete for iron during an infection.

Revisiting Proton Pump Inhibitors as Chemoprophylaxis Against the Progression of Barrett's Esophagus.

Purpose Of Review: Barrett's esophagus (BE) is associated with chronic gastroesophageal reflux disease and is a known precursor to esophageal adenocarcinoma. While endoscopic surveillance strategies and the role for endoscopic eradication therapy have been well established, there has been much interest in identifying chemopreventive agents to disrupt or halt the metaplasia-dysplasia-carcinoma sequence in patients with BE.

Recent Findings: No pharmacological agent has held more hope in reducing the risk of neoplastic progression in BE than proton pump inhibitors (PPIs).

Online Well-Being Group Coaching Program for Women Physician Trainees: A Randomized Clinical Trial.

Importance: Physician burnout disproportionately affects women physicians and begins in training. Professional coaching may improve well-being, but generalizable evidence is lacking.

Objective: To assess the generalizability of a coaching program (Better Together Physician Coaching) in a national sample of women physician trainees.

Advancing Fintech through a transdisciplinary approach.

The term "Fintech" is a portmanteau of "financial technology." Fintech is an emerging field that can be advanced through interdisciplinary collaboration, contributing to the fourth industrial revolution, known as Industry 4.0 (Doherty & Stephens, 2023).

Peripheral site modification in a family of dinuclear [Dy(hynad)(NO)(sol)] single-molecule magnets bearing a {Dy(μ-OR)} diamond-shaped core and exhibiting dissimilar magnetic dynamics.

The first use of the organic chelate -hydroxy-1,8-naphthalimide (hynadH) in Dy chemistry has unveiled access to a synthetic 'playground' composed of four new dinuclear complexes, all of which possess the same planar {Dy(μ-OR)} diamond-shaped core, resulting from the bridging and chelating capacity of the hynad groups. The structural stability of the central {Dy} core has allowed for the modulation of the peripheral coordination sites of the metal ions, and specifically the NO/hynad ratio of capping groups, thus affording the compounds [Dy(hynad)(NO)(DMF)] (1), (MeN)[Dy(hynad)(NO)] (2), [Dy(hynad)(NO)(HO)] (3), and [Dy(hynad)(HO)] (4). Because of the chemical and structural modifications in the series 1-4, the Dy coordination polyhedra are also dissimilar, comprising the muffin (1 and 3), tetradecahedral (2), and spherical tricapped trigonal prismatic (4) geometries.

p53 Gain-of-Function Mutation Induces Metastasis via BRD4-Dependent CSF-1 Expression.

Unlabelled: TP53 mutations are frequent in esophageal squamous cell carcinoma (ESCC) and other SCCs and are associated with a proclivity for metastasis. Here, we report that colony-stimulating factor-1 (CSF-1) expression is upregulated significantly in a p53-R172H-dependent manner in metastatic lung lesions of ESCC. The p53-R172H-dependent CSF-1 signaling, through its cognate receptor CSF-1R, increases tumor cell invasion and lung metastasis, which in turn is mediated in part through Stat3 phosphorylation and epithelial-to-mesenchymal transition (EMT).

Magnetic coupling between Fe(NO) spin probe ligands through diamagnetic Ni, Pd and Pt tetrathiolate bridges.

Reaction of the nitrosylated-iron metallodithiolate ligand, paramagnetic (NO)Fe(NS), with [M(CHCN)][BF] salts (M = Ni, Pd, and Pt; = 4 or 6) affords di-radical tri-metallic complexes in a stairstep type arrangement ([FeMFe], M = Ni, Pd, and Pt), with the central group 10 metal held in a MS square plane. These isostructural compounds have nearly identical (NO) stretching values, isomer shifts, and electrochemical properties, but vary in their magnetic properties. Despite the intramolecular Fe⋯Fe distances of 6 Å, antiferromagnetic coupling is observed between {Fe(NO)} units as established by magnetic susceptibility, EPR, and DFT studies.

Synthesis and exceptional operational durability of polyaniline-inspired conductive ladder polymers.

Ladder-type structures can impart exceptional stability to polymeric electronic materials. This article introduces a new class of conductive polymers featuring a fully ladder-type backbone. A judicious molecular design strategy enables the synthesis of a low-defect ladder polymer, which can be efficiently oxidized and acid-doped to achieve its conductive state.

Key Genetic Determinants Driving Esophageal Squamous Cell Carcinoma Initiation and Immune Evasion.

Background & Aims: Despite recent progress in identifying aberrant genetic and epigenetic alterations in esophageal squamous cell carcinoma (ESCC), the mechanism of ESCC initiation remains unknown.

Methods: Using CRISPR/Cas 9-based genetic ablation, we targeted 9 genes (TP53, CDKN2A, NOTCH1, NOTCH3, KMT2D, KMT2C, FAT1, FAT4, and AJUBA) in murine esophageal organoids. Transcriptomic phenotypes of organoids and chemokine released by organoids were analyzed by single-cell RNA sequencing.