Personalized, autologous neoantigen-specific T cell therapy in metastatic melanoma: a phase 1 trial.

New treatment approaches are warranted for patients with advanced melanoma refractory to immune checkpoint blockade (ICB) or BRAF-targeted therapy. We designed BNT221, a personalized, neoantigen-specific autologous T cell product derived from peripheral blood, and tested this in a 3 + 3 dose-finding study with two dose levels (DLs) in patients with locally advanced or metastatic melanoma, disease progression after ICB, measurable disease (Response Evaluation Criteria in Solid Tumors version 1.1) and, where appropriate, BRAF-targeted therapy.

Intraperitoneal delivery of cannabidiol (CBD) and Δ-tetrahydocannabinol (THC) promotes papillomavirus infections in athymic nude mice.

We used our mouse papillomavirus (MmuPV1) model to test the hypothesis that two primary psychoactive ingredients of marijuana, Δ-tetrahydrocannabinol (THC) and cannabidiol (CBD), promote papillomavirus persistence in the oral mucosa of infected mice. We conducted intraperitoneal (ip) injections of a moderate dose (3 mg/kg) of either CBD and/or THC in both male and female athymic nude mice and followed the mice up to 20 weeks post-infection. These doses are comparable to what is estimated for human conventional cannabis consumption.

Real-World Study of Ragweed Sublingual Immunotherapy in Hungary.

Background: Ragweed () has become invasive in Europe, causing significant respiratory issues. Subcutaneous allergen immunotherapy (SCIT) has long been used to manage pollen allergies, but sublingual immunotherapy (SLIT) has gained interest.

Objective: This study aimed to evaluate the clinical benefits of ragweed SLIT under real-world in a cohort of Hungarian patients allergic to ragweed pollen.

Effect of aflatoxin B1 and sterigmatocystin on DNA repair genes in common carp.

The present study aimed to investigate the short-time (24 h) effect of aflatoxin B1 (AFB1) and sterigmatocystin (STC) on the expression of hsp70, p53, gadd45, and ogg1 genes in common carp hepatopancreas. Our results showed that aflatoxin B1 and sterigmatocystin can stimulate the expression of DNA repair genes, mainly by hour 24. This significant finding contributes to our understanding of the short-term effects of these mycotoxins on ogg1 genes in common carp hepatopancreas.

Monitoring mouse papillomavirus-associated cancer development using longitudinal Pap smear screening.

Unlabelled: A substantial percentage of the population remains at risk for cervical cancer due to pre-existing human papillomavirus (HPV) infections, despite prophylactic vaccines. Early diagnosis and treatment are crucial for better disease outcomes. The development of new treatments heavily relies on suitable preclinical model systems.

Exposure to a Combination of Mycotoxins Leads to Lipid Peroxidation and Influences Antioxidant Defenses, Fatty Acid Composition of Phospholipids, and Renal Histology in Laying Hens.

The effects of combined short-term (3 days) exposure to mycotoxins at both the EU recommended limit (T-2/HT-2 toxin: 0.25 mg/kg; DON/3-AcDON/15-AcDON: 5 mg/kg; FB: 20 mg/kg) and twice the dose (T-2/HT-2 toxin: 0.5 mg/kg, DON/3-AcDON/15-AcDON: 10 mg/kg, and FB: 40 mg/kg feed) on the kidneys of laying hens were examined.

Current evidence of the economic value of One Health initiatives: A systematic literature review.

Funding and financing for One Health initiatives at country level remain challenging as investments commonly require demonstrated evidence of economic value or returns. The objectives of this review were to i) identify, critically analyse and summarise quantitative evidence of the net economic value of One Health initiatives; ii) document methodologies commonly used in the scientific literature; and iii) describe common challenges and any evidence gaps. Scientific databases were searched for published literature following the PRISMA guidelines and an online survey and workshop with subject matter experts were used to identify relevant grey literature.

New Computerized Planning Algorithm and Clinical Testing of Optimized Nuss Bar Design for Patients with Pectus Excavatum.

BACKGROUND Computer-aided design (CAD) has been used in the Nuss procedure to determine the bar length and shape. Despite computer aid, the shape and design remain quite intuitive. We tested a new algorithm to determine the optimal bar shape.

FLT3L governs the development of partially overlapping hematopoietic lineages in humans and mice.

FMS-related tyrosine kinase 3 ligand (FLT3L), encoded by FLT3LG, is a hematopoietic factor essential for the development of natural killer (NK) cells, B cells, and dendritic cells (DCs) in mice. We describe three humans homozygous for a loss-of-function FLT3LG variant with a history of various recurrent infections, including severe cutaneous warts. The patients' bone marrow (BM) was hypoplastic, with low levels of hematopoietic progenitors, particularly myeloid and B cell precursors.

The Effect of Combined Exposure of Mycotoxins on Lipid Peroxidation, Antioxidant Defense, Fatty Acid Profile, and Histopathology in Laying Hens' Liver.

Fumonisin B1, T-2 toxin, and deoxynivalenol are frequently detected in feed materials. The mycotoxins induce free radical formation and, thereby, lipid peroxidation. The effects of mycotoxin exposure at the EU recommended limit (T-2/HT-2 toxin: 0.

Curcumin mitigates ochratoxin A-induced oxidative stress and alters gene expression in broiler chicken liver and kidney.

The study aimed to evaluate the effect of curcumin (CURC) supplementation on broiler chickens exposed to ochratoxin A (OTA), by examining biochemical parameters and the expression of glutathione redox system genes and their regulation. OTA reduced glutathione content in the liver while increasing glutathione peroxidase activity. CURC showed no significant effects.

The Effects of T-2 Toxin, Deoxynivalenol, and Fumonisin B1 on Oxidative Stress-Related Genes in the Kidneys of Laying Hens.

In the context of nephrotoxic risks associated with environmental contaminants, this study focused on the impact of mycotoxin exposure on the renal health of laying hens, with particular attention to oxidative stress pathways. Sixty laying hens were assigned to three groups-a control group (CON), a low-dose mycotoxin group (LOW), and a high-dose mycotoxin group (HIGH)-and monitored for 72 h. Mycotoxin contamination involved T-2/HT-2 toxin, DON/3-AcDON/15-AcDON, and FB1 at their EU-recommended levels (low mix) and at double doses (high mix).

Gender Difference in DNA Damage Induced by the Environmental Carcinogen Dibenzo[]chrysene Individually and in Combination with Mouse Papillomavirus Infection in the Mouse Oral Cavity.

Tobacco smoking and human papillomavirus infection are established etiological agents in the development of head and neck squamous cell carcinoma (HNSCC). The incidence and mortality of HNSCC are higher in men than women. To provide biochemical basis for sex differences, we tested the hypothesis that carcinogen treatment using dibenzo[]chrysene, which is an environmental pollutant and tobacco smoke constituent, in the absence or presence of the mouse papillomavirus infection results in significantly higher levels of DNA damage in the oral cavity in male than in female mice.

Immune Responses in Oral Papillomavirus Clearance in the MmuPV1 Mouse Model.

Human papillomavirus (HPV)-induced oropharyngeal cancer now exceeds HPV-induced cervical cancer, with a noticeable sex bias. Although it is well established that women have a more proficient immune system, it remains unclear whether immune control of oral papillomavirus infections differs between sexes. In the current study, we use genetically modified mice to target CCR2 and Stat1 pathways, with the aim of investigating the role of both innate and adaptive immune responses in clearing oral papillomavirus, using our established papillomavirus (MmuPV1) infection model.

Multi-Fusarium mycotoxin exposure activates Nrf2 and Ahr pathway in the liver of laying hens.

This study investigates gene expression changes in laying hens exposed to trichothecene mycotoxins, known to induce oxidative stress and affect xenobiotic transformation and antioxidants. A 3-day feeding trial tested low and high doses of T-2/HT-2 toxin, DON/3-AcDON/15-AcDON, and FB1 in hen feed. Results showed increased expression of AHR, AHRR, HSP90, and CYP1A2 genes on days 2 and 3, suggesting a response to mycotoxin exposure.

The Rabies Free Burkina Faso initiative: an example of how one health-oriented civil society organizations can contribute towards the achievement of the rabies zero by 30 goal.

While technologies, tools and expertise have proven that countries can be made safe from dog-mediated human rabies, the disease remains a major public health threat in Burkina Faso. The paper reports the experience and success stories of Rabies Free Burkina Faso, an initiative established in 2020 as an example of civil society organization that promotes One Health for integrated rabies control in Africa. As recommended in the Global strategic plan, rabies elimination requires a systematic One Health approach, enhancing pre-exposure and postexposure prophylaxis, dog population management, dog vaccination, awareness raising, diagnosis, surveillance, funding as well as policies and regulations.

One Health early warning and response system for zoonotic diseases outbreaks: Emphasis on the involvement of grassroots actors.

Background: Emerging and reemerging zoonotic diseases have become a global concern due to their frequent occurrence. Large delays between onset of emerging zoonotic disease outbreaks and their reporting and control are indicative of weak animal and human health systems.

Objectives: The objective of this paper is to tackle the time delay by suggesting a One Health Early Warning and Response System (OH-EWRS) aiming at improving the surveillance and notification of zoonotic diseases by strengthening 'bottom-up' approaches and systems for early detection, especially in hot spot areas where they emerge.

The Co-Occurrence of T-2 Toxin, Deoxynivalenol, and Fumonisin B1 Activated the Glutathione Redox System in the EU-Limiting Doses in Laying Hens.

Different mycotoxins in feed lead to combined exposure, increasing adverse effects on animal health. Trichothecene mycotoxins have been associated with inducing oxidative stress, which is neutralized by the glutathione system within the antioxidant defense, depending on the dose and duration of exposure. T-2 toxin, deoxynivalenol (DON), and fumonisin B1 (FB1) are commonly found in feed commodities simultaneously.

United Against Rabies Forum: The first 2 years.

Rabies continues to kill an estimated 59,000 people annually, with up to 99% of human cases transmitted by domestic dogs. The elimination of human deaths from dog-mediated rabies is achievable by applying a One Health approach, and the framework to do this is outlined in Zero by 30: the Global Strategic Plan to end human deaths from dog-mediated rabies by 2030. To build on this global goal, and implement the approaches set out in Zero by 30, the United Against Rabies Forum was launched in 2020.

Coordinated surveillance system under the One Health approach for cross-border pathogens that threaten the Union - options for sustainable surveillance strategies for priority pathogens.

This report provides guidance for Member states who plan to submit applications under the work programme 'CP-g-22-04.01 Direct grants to Member States' authorities'. The priority pathogens on which the coordinated surveillance under the grant initiative shall focus have been identified in a prioritisation exercise with Member States and ECDC.

Fumonisin B Series Mycotoxins' Dose Dependent Effects on the Porcine Hepatic and Pulmonary Phospholipidome.

Male weaned piglets n = 6/group were fed Fumonisin B (FBs) mycotoxins at 0, 15, or 30 mg/kg diet for 3 weeks to assess the fatty acid (FA) composition of membrane lipid classes, lipid peroxidation, and histomorphological changes in the liver and lung. Growth performance and lipid peroxidation were unaltered, but histomorphological lesion scores increased in the liver. Linear dose-response was detected in liver phosphatidylcholines for C16:1n7, C18:1n9, and total monounsaturation and in lungs for C22:6n3, total n-3 and n-3:n-6, in pulmonary phosphatidylserines C20:0 and C24:0.

Personalized neoantigen vaccine NEO-PV-01 with chemotherapy and anti-PD-1 as first-line treatment for non-squamous non-small cell lung cancer.

Neoantigens arising from mutations in tumor DNA provide targets for immune-based therapy. Here, we report the clinical and immune data from a Phase Ib clinical trial of a personalized neoantigen-vaccine NEO-PV-01 in combination with pemetrexed, carboplatin, and pembrolizumab as first-line therapy for advanced non-squamous non-small cell lung cancer (NSCLC). This analysis of 38 patients treated with the regimen demonstrated no treatment-related serious adverse events.

Passive Immunization with a Single Monoclonal Neutralizing Antibody Protects against Cutaneous and Mucosal Mouse Papillomavirus Infections.

We have established a mouse papillomavirus (MmuPV1) model that induces both cutaneous and mucosal infections and cancers. In the current study, we use this model to test our hypothesis that passive immunization using a single neutralizing monoclonal antibody can protect both cutaneous and mucosal sites at different time points after viral inoculation. We conducted a series of experiments involving the administration of either a neutralizing monoclonal antibody, MPV.