Sickle Trait and Alpha Thalassemia Increase NOS-Dependent Vasodilation of Human Arteries Through Disruption of Endothelial Hemoglobin-eNOS Interactions.

Background: Severe malaria is associated with impaired nitric oxide (NO) synthase (NOS)-dependent vasodilation, and reversal of this deficit improves survival in murine models. Malaria might have selected for genetic polymorphisms that increase endothelial NO signaling and now contribute to heterogeneity in vascular function among humans. One protein potentially selected for is alpha globin, which, in mouse models, interacts with endothelial NOS (eNOS) to negatively regulate NO signaling.

Diagnosis and management of subungual and periungual verruca: A clinical review.

Nail unit verruca is the most common nail tumor encountered in clinical practice and may be highly distressing to patients due to reduced functionality, cosmesis, and stigmatization. Subungual and periungual verrucae present a challenge for treatment compared to cutaneous warts of other sites and recurrence rates are high. The risk of spread to other skin and mucosal areas inherent to all warts may be increased given location on the fingertips.

Lessons learned from 150 total gastrectomies for prevention of cancer.

Background: Prophylactic total gastrectomy (PTG) is performed in carriers of CDH1 pathogenic and likely pathogenic (P/LP) variants and is becoming more frequent with broader use of germline genetic testing. There is an unmet need to standardize care and enhance outcomes among patients undergoing surgery for the prevention of gastric cancer.

Methods: This was a retrospective analysis of 150 individuals with germline CDH1 P/LP variants who underwent PTG as part of a prospective natural history study from October 2017 to May 2023.

A New Twist on the Surgeon's Knot: Quantifying Suture Security.

Background: The reliability and security of surgical knots play a critical role in wound closure and healing. A surgeon's knot, created by a modification of the square knot in which an extra 'twist' is added to the initial throw, is often used to increase friction and provide stability of the tissue as the knot is completed.

Objective: The purpose of this study was to quantify the security of sutures, as influenced by varying numbers of initial twists in a surgeon's knot.

A Decreased Appetite for Prophylactic Total Gastrectomy.

Total gastrectomy should be performed less often in germline CDH1 variant carriers based on mounting clinical evidence.

Extensive Local Geographic Variation in Locoweed Toxin Produced by a Fungal Endophyte.

Legumes are notorious for coevolutionary arms races where chemical defenses are employed to ward off herbivores-particularly insect seed predators. Locoweeds are legumes containing the toxic alkaloid swainsonine which can poison livestock, but its role as a deterrent for insects is unknown. Swainsonine is produced by the fungal endophyte Alternaria section Undifilum, and the chemical composition of the toxin has been well characterized.

Extrahepatic biliary neuroendocrine tumors: A national cancer database analysis.

Background: Extrahepatic biliary neuroendocrine tumors (EBNETs) are rare. We aimed to characterize EBNETs including factors associated with survival.

Methods: The National Cancer Database was queried for patients with EBNETs from 2004 to 2016.

Does generative artificial intelligence pose a risk to performance validity test security?

Objective: We examined the performance validity test (PVT) security risk presented by artificial intelligence (AI) chatbots asking questions about neuropsychological evaluation and PVTs on two popular generative AI sites.

Method: In 2023 and 2024, multiple questions were posed to ChatGPT-3 and Bard (now Gemini). One set started generally and refined follow-up questions based on AI responses.

Hepatic artery infusion pump (HAIP) therapy in combination with targeted delivery of IL-12 for patients with metastatic colorectal cancer or intrahepatic cholangiocarcinoma: a phase II trial protocol.

Background: Treatment of advanced liver tumors remains challenging. Although immune checkpoint inhibition has revolutionized treatment for many cancers, responses in colorectal liver metastases and biliary tract cancers remain suboptimal. Investigation into additional immunomodulatory therapies for these cancers is needed.

Predicting Survival in Mucinous Adenocarcinoma of the Appendix: Demographics, Disease Presentation, and Treatment Methodology.

Background: Mucinous adenocarcinoma of the appendix (MACA) follows a complex disease course with variable survival. Large-scale predictive modeling may determine subtle yet important prognostic factors otherwise unseen in smaller cohort analyses.

Methods: Patients with MACA were identified from the Surveillance, Epidemiology, and End Results (SEER) Research Plus database (2005-2019).

Germline CDH1 Variants and Lifetime Cancer Risk.

Importance: Approximately 1% to 3% of gastric cancers and 5% of lobular breast cancers are hereditary. Loss of function CDH1 gene variants are the most common gene variants associated with hereditary diffuse gastric cancer and lobular breast cancer. Previously, the lifetime risk of gastric cancer was estimated to be approximately 25% to 83% and for breast cancer it was estimated to be approximately 39% to 55% in individuals with loss of function CDH1 gene variants.

Cutaneous Applications of the Antiviral Drug Cidofovir: A Review.

Cidofovir, an antiviral drug approved for cytomegalovirus retinitis, has emerged as an alternative treatment option for virally induced cutaneous and mucocutaneous conditions, as well as being trialed as a treatment for select neoplasms. In this review, we highlight the existing evidence, clinical uses, and rationale of using cidofovir for the treatment of cutaneous pathologies. A PubMed database literature search was conducted to identify relevant articles for inclusion in this review.

Stool Protein Mass Spectrometry Identifies Biomarkers for Early Detection of Diffuse-type Gastric Cancer.

There is a high unmet need for early detection approaches for diffuse gastric cancer (DGC). We examined whether the stool proteome of mouse models of gastric cancer (GC) and individuals with hereditary diffuse gastric cancer (HDGC) have utility as biomarkers for early detection. Proteomic mass spectrometry of the stool of a genetically engineered mouse model driven by oncogenic KrasG12D and loss of p53 and Cdh1 in gastric parietal cells [known as Triple Conditional (TCON) mice] identified differentially abundant proteins compared with littermate controls.

Refusals and Requests: In Defense of Consistency.

Physicians place significant weight on the distinction between acts and omissions. Most believe that autonomous refusals for procedures, such as blood transfusions and resuscitation, ought to be respected, but they feel no similar obligation to accede to requests for treatment that will, in the physician's opinion, harm the patient (e.g.

The European Lead Factory: Results from a decade of collaborative, public-private, drug discovery programs.

The European Lead Factory (ELF) is a consortium of universities and small and medium-sized enterprises (SMEs) dedicated to drug discovery, and the pharmaceutical industry. This unprecedented consortium provides high-throughput screening, triage, and hit validation, including to non-consortium members. The ELF library was created through a novel compound-sharing model between nine pharmaceutical companies and expanded through library synthesis by chemistry-specialized SMEs.

Genome-wide profiling of transcription factor activity in primary liver cancer using single-cell ATAC sequencing.

Primary liver cancer (PLC) consists of two main histological subtypes; hepatocellular carcinoma (HCC) and intrahepatic cholangiocarcinoma (iCCA). The role of transcription factors (TFs) in malignant hepatobiliary lineage commitment between HCC and iCCA remains underexplored. Here, we present genome-wide profiling of transcription regulatory elements of 16 PLC patients using single-cell assay for transposase accessible chromatin sequencing.

Perceptions of Readiness for Practice After Complex General Surgical Oncology Fellowship: A Survey Study.

Background: Surgical subspecialty training aims to meet the needs of practicing surgeons and their communities. This study investigates career preparedness of Complex General Surgical Oncology (CGSO) fellowship graduates, identifies factors associated with practice readiness, and explores potential opportunities to improve the current training model.

Methods: The Society of Surgical Oncology partnered with the National Cancer Institute to conduct a 36-question survey of CGSO fellowship graduates from 2012 to 2022.

Protocol for isolation of signet ring cells from human gastric mucosa.

More than 90% of individuals with germline pathogenic CDH1 variants will harbor occult, microscopic foci of signet ring cell carcinomas capable of progressing to advanced diffuse-type gastric cancer. Here, we present a protocol for high viability suspension of signet ring cells from human gastric tissue. We describe the steps for gastric mucosa isolation and tissue dissociation.