A Herpes Simplex Virus Type-1-Derived Influenza Vaccine Induces Balanced Adaptive Immune Responses and Protects Mice From Lethal Influenza Virus Challenge.

Influenza virus is a major respiratory viral pathogen responsible for the deaths of hundreds of thousands worldwide each year. Current vaccines provide protection primarily by inducing strain-specific antibody responses with the requirement of a match between vaccine strains and circulating strains. It has been suggested that anti-influenza T-cell responses, in addition to antibody responses may provide the broadest protection against different flu strains.

Evaluation of a Skin Barrier Ring With Assisted Flow: A Prospective Cohort Study.

Purpose: The purpose of this study was to assess the effect of a skin barrier ring with assisted flow in preventing peristomal skin complications (PSCs) in patients with an ileostomy and to evaluate the participants' perceptions of the device.

Design: Single-group, prospective cohort study.

Subjects And Setting: Both inpatients and outpatients with newly created (n = 14) or established (n = 1) ileostomies were recruited from 2 clinical sites in the United States: one was an academic teaching hospital system in the Midwestern United States and the second was a teaching hospital located in the Southeastern United States.

Unlocking the Potential of Kinase Targets in Cancer: Insights from CancerOmicsNet, an AI-Driven Approach to Drug Response Prediction in Cancer.

Deregulated protein kinases are crucial in promoting cancer cell proliferation and driving malignant cell signaling. Although these kinases are essential targets for cancer therapy due to their involvement in cell development and proliferation, only a small part of the human kinome has been targeted by drugs. A comprehensive scoring system is needed to evaluate and prioritize clinically relevant kinases.

Artificial intelligence to guide precision anticancer therapy with multitargeted kinase inhibitors.

Background: Vast amounts of rapidly accumulating biological data related to cancer and a remarkable progress in the field of artificial intelligence (AI) have paved the way for precision oncology. Our recent contribution to this area of research is CancerOmicsNet, an AI-based system to predict the therapeutic effects of multitargeted kinase inhibitors across various cancers. This approach was previously demonstrated to outperform other deep learning methods, graph kernel models, molecular docking, and drug binding pocket matching.

An Attenuated HSV-1-Derived Malaria Vaccine Expressing Liver-Stage Exported Proteins Induces Sterilizing Protection against Infectious Sporozoite Challenge.

Here, we present the construction of an attenuated herpes simplex virus type-1 (HSV-1)-vectored vaccine, expressing three liver-stage (LS) malaria parasite exported proteins (EXP1, UIS3 and TMP21) as fusion proteins with the VP26 viral capsid protein. Intramuscular and subcutaneous immunizations of mice with a pooled vaccine, composed of the three attenuated virus strains expressing each LS antigen, induced sterile protection against the intravenous challenge of 17X-NL salivary gland sporozoites. Our data suggest that this malaria vaccine may be effective in preventing malaria parasite infection using practical routes of immunization in humans.

Utility of a Recombinant HSV-1 Vaccine Vector for Personalized Cancer Vaccines.

Current approaches to cancer immunotherapy include immune checkpoint inhibitors, cancer vaccines, and adoptive cellular therapy. These therapies have produced significant clinical success for specific cancers, but their efficacy has been limited. Oncolytic virotherapy (OVT) has emerged as a promising immunotherapy for a variety of cancers.

Noncoding RNAs and Deep Learning Neural Network Discriminate Multi-Cancer Types.

Detecting cancers at early stages can dramatically reduce mortality rates. Therefore, practical cancer screening at the population level is needed. To develop a comprehensive detection system to classify multiple cancer types, we integrated an artificial intelligence deep learning neural network and noncoding RNA biomarkers selected from massive data.

The impact of neoadjuvant concurrent chemoradiation on exosomal markers (CD63 and CD9) expression and their prognostic significance in patients with rectal adenocarcinoma.

Introduction: Exosomes have pivotal roles in cancer development. The impact of neoadjuvant concurrent chemoradiation (NCCR) on exosomal markers (CD63 and CD9) expression and their prognostic significance in patients with rectal adenocarcinoma are yet to be explored.

Materials And Methods: Between 2015 and 2018, 33 patients had rectal adenocarcinoma treated with NCCR and had pre-NCCR biopsy and post-NCCR resected rectum.

The Effect of Herpes Simplex Virus-Type-1 (HSV-1) Oncolytic Immunotherapy on the Tumor Microenvironment.

The development of cancer causes disruption of anti-tumor immunity required for surveillance and elimination of tumor cells. Immunotherapeutic strategies aim for the restoration or establishment of these anti-tumor immune responses. Cancer immunotherapies include immune checkpoint inhibitors (ICIs), adoptive cellular therapy (ACT), cancer vaccines, and oncolytic virotherapy (OVT).

Anti-viral immunity in the tumor microenvironment: implications for the rational design of herpes simplex virus type 1 oncolytic virotherapy.

Purpose Of Review: The design of novel herpes simplex type I (HSV-1)-derived oncolytic virotherapies is a balancing act between safety, immunogenicity and replicative potential. We have undertaken this review to better understand how these considerations can be incorporated into rational approaches to the design of novel herpesvirus oncolytic virotherapies.

Recent Findings: Several recent papers have demonstrated that enhancing the potential of HSV-1 oncolytic viruses to combat anti-viral mechanisms present in the tumor microenvironment leads to greater efficacy than their parental viruses.

Oliceridine is Associated with Reduced Risk of Vomiting and Need for Rescue Antiemetics Compared to Morphine: Exploratory Analysis from Two Phase 3 Randomized Placebo and Active Controlled Trials.

Introduction: Use of parenteral opioids is a major risk factor for postoperative nausea and vomiting. Conventional opioids bind to µ-opioid receptors (MOR), stimulate both the G-protein signaling (achieving analgesia); and the β-arrestin pathway (associated with opioid-related adverse effects). Oliceridine, a next-generation IV opioid, is a G-protein selective MOR agonist, with limited recruitment of β-arrestin.

Novel Oncolytic Herpes Simplex Virus 1 VC2 Promotes Long-Lasting, Systemic Anti-melanoma Tumor Immune Responses and Increased Survival in an Immunocompetent B16F10-Derived Mouse Melanoma Model.

Oncolytic virotherapy (OVT) is now understood to be an immunotherapy that uses viral infection to liberate tumor antigens in an immunogenic context to promote the development of antitumor immune responses. The only currently FDA-approved oncolytic virotherapy, T-Vec, is a modified type 1 herpes simplex virus (HSV-1). While T-Vec is associated with limited response rates, its modest efficacy supports the continued development of novel OVT viruses.

Low Incidence of Postoperative Respiratory Depression with Oliceridine Compared to Morphine: A Retrospective Chart Analysis.

Background: Oliceridine, an investigational IV opioid, is a first-in-class G-protein selective agonist at the -opioid receptor. The G-protein selectivity results in potent analgesia with less recruitment of -arrestin, a signaling pathway associated with opioid-related adverse events (ORAEs). In randomized controlled studies in both hard and soft tissue models yielding surgical pain, oliceridine provided effective analgesia with a potential for an improved safety and tolerability profile at equianalgesic doses to morphine.

Usefulness of Restaging Pelvis Magnetic Resonance Imaging After Neoadjuvant Concurrent Chemoradiotherapy in Patients With Locally Advanced Rectal Cancer.

Introduction: In patients with locally advanced rectal cancer, restaging pelvis magnetic resonance imaging (MRI) after neoadjuvant concurrent chemoradiotherapy is recommended despite its limited accuracy in predicting pathologic T (ypT) and N (ypN) stage. Neoadjuvant rectal (NAR) score is a novel short-term surrogate endpoint for disease-free survival (DFS) and overall survival (OS). We tested the agreement between restaging MRI T (yT) and N (yN) with ypT and ypN stages, respectively, and explored the prognostic significance of restaging MRI NAR (mNAR) score.

Intramuscular vaccination of mice with the human herpes simplex virus type-1(HSV-1) VC2 vaccine, but not its parental strain HSV-1(F) confers full protection against lethal ocular HSV-1 (McKrae) pathogenesis.

Herpes simplex virus type-1 (HSV-1) can cause severe ocular infection and blindness. We have previously shown that the HSV-1 VC2 vaccine strain is protective in mice and guinea pigs against genital herpes infection following vaginal challenge with HSV-1 or HSV-2. In this study, we evaluated the efficacy of VC2 intramuscular vaccination in mice against herpetic keratitis following ocular challenge with lethal human clinical strain HSV-1(McKrae).

Identification and Visualization of Functionally Important Domains and Residues in Herpes Simplex Virus Glycoprotein K(gK) Using a Combination of Phylogenetics and Protein Modeling.

Alphaherpesviruses are a subfamily of herpesviruses that include the significant human pathogens herpes simplex viruses (HSV) and varicella zoster virus (VZV). Glycoprotein K (gK), conserved in all alphaherpesviruses, is a multi-membrane spanning virion glycoprotein essential for virus entry into neuronal axons, virion assembly, and pathogenesis. Despite these critical functions, little is known about which gK domains and residues are most important for maintaining these functions across all alphaherpesviruses.

Endoscopic technique for closure of enterocutaneous fistulas.

Background And Objectives: Endoscopic over the scope clip (OTSC) closure represents a new technique for endoscopic management of enteric bleeding and tissue defects such as anastomotic leaks and enterocutaneous (EC) fistulas. We aim to describe our technical approach for OTSC closure of EC fistulas and convey our outcomes.

Methods And Procedures: This retrospective review includes ten patients who underwent OTSC application for EC fistulas by surgical endoscopists at a US tertiary care hospital from July 2015 to October 2017.

Identifying molecular contributors to autofluorescence of neoplastic and normal colon sections using excitation-scanning hyperspectral imaging.

Autofluorescence, the endogenous fluorescence present in cells and tissues, has historically been considered a nuisance in biomedical imaging. Many endogenous fluorophores, specifically, collagen, elastin, nicotinamide adenine dinucleotide, and flavin adenine dinucleotide (FAD), are found throughout the human body. In fluorescence imaging scenarios, these signals can be prohibitive as they can outcompete signals introduced for diagnostic purposes.

Factors Affecting Growth Kinetics and Spontaneous Metastasis in the B16F10 Syngeneic Murine Melanoma Model.

Melanoma is an immunogenic tumor that can metastasize quickly to proximal and distal sites, thus complicating the application of therapeutic modalities. Numerous mouse model systems have been used to gain understanding of the immunobiology and metastatic potential of melanoma. Here, we report the optimization of a syngeneic mouse melanoma model protocol using the mouse B16-derived melanoma cell line B16F10 that ensures the production of tumors on mice pinnae that are similar in size between animals and that enlarge in a time-dependent manner.

First Impressions-the Potential of Altering Initial Host-Virus Interactions for Rational Design of Herpesvirus Vaccine Vectors.

Purpose: The earliest host-virus interactions occur during virus attachment and entry into cells. These initial steps in the virus lifecycle influence the outcome of infection beyond delivery of the viral genome into the cell. Herpesviruses alter host signaling pathways and processes during attachment and entry to facilitate virus infection and modulate innate immune responses.

Safety and Efficacy of Bupivacaine HCl Collagen-Matrix Implant (INL-001) in Open Inguinal Hernia Repair: Results from Two Randomized Controlled Trials.

Introduction: Surgical site infiltration with bupivacaine results in short-lived analgesia. The MATRIX-1 and MATRIX-2 studies examined the efficacy and safety of the bioresorbable bupivacaine HCl collagen-matrix implant (INL-001) for postsurgical pain after open inguinal hernia repair. INL-001, designed to provide early and extended delivery of bupivacaine, provides prolonged duration of perioperative analgesia.

The Diagnostic and Therapeutic Challenge of Anal Intraepithelial Neoplasia.

Purpose Of Review: No single modality of care serves as the defined best practice for the treatment of anal intraepithelial neoplasia (AIN). This review aims to present the common treatment modalities germane to AIN while considering evolving evidence.

Recent Findings: AIN affords an opportunity to evaluate and treat patients before the development of invasive diseases.

Intramuscular vaccination of guinea pigs with the live-attenuated human herpes simplex vaccine VC2 stimulates a transcriptional profile of vaginal Th17 and regulatory Tr1 responses.

Herpes simplex virus is a common causative agent of oral and genital diseases. Novel vaccines and therapeutics are needed to combat herpes infections especially after the failure of subunit vaccines in human clinical trials. We have shown that the live-attenuated HSV-1 VC2 vaccine strain is unable to establish latency in vaccinated animals and produces a robust immune response capable of completely protecting mice against lethal vaginal HSV-1 or HSV-2 infections.

The Amino Terminus of Herpes Simplex Virus 1 Glycoprotein K (gK) Is Required for gB Binding to Akt, Release of Intracellular Calcium, and Fusion of the Viral Envelope with Plasma Membranes.

Previously, we have shown that the amino terminus of glycoprotein K (gK) binds to the amino terminus of gB and that deletion of the amino-terminal 38 amino acids of gK prevents herpes simplex virus 1 (HSV-1) infection of mouse trigeminal ganglia after ocular infection and virus entry into neuronal axons. Recently, it has been shown that gB binds to Akt during virus entry and induces Akt phosphorylation and intracellular calcium release. Proximity ligation and two-way immunoprecipitation assays using monoclonal antibodies against gB and Akt-1 phosphorylated at S473 [Akt-1(S473)] confirmed that HSV-1(McKrae) gB interacted with Akt-1(S473) during virus entry into human neuroblastoma (SK-N-SH) cells and induced the release of intracellular calcium.