KEYNOTE - D36: Personalized immunotherapy with a neoepitope vaccine, EVX-01 and pembrolizumab in advanced melanoma

Despite improvements made with checkpoint inhibitor (CPI) therapy, a need for new approaches to improve outcomes for patients with unresectable or metastatic melanoma remains. EVX-01, a personalized neoepitope vaccine, combined with pembrolizumab treatment, holds the potential to fulfill this need. Here we present the rationale and novel design behind the KEYNOTE - D36 trial: an open label, single arm, phase II trial aiming to establish the clinical proof of concept and evaluate the safety of EVX-01 in combination with pembrolizumab in CPI naive patients with unresectable or metastatic melanoma. The primary objective is to evaluate if EVX-01 improves best overall response after initial stable disease or partial response to pembrolizumab treatment, in patients with advanced melanoma. The novel end points ensure a decisive readout which may prove helpful before making major investments in phase III trials with limited phase I data. Clinical Trial Registration: NCT05309421 (ClinicalTrials.gov)

Unexpected detection of SARS-CoV-2 antibodies in the prepandemic period in Italy

There are no robust data on the real onset of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and spread in the prepandemic period worldwide. We investigated the presence of SARS-CoV-2 receptor-binding domain (RBD)–specific antibodies in blood samples of 959 asymptomatic individuals enrolled in a prospective lung cancer screening trial between September 2019 and March 2020 to track the date of onset, frequency, and temporal and geographic variations across the Italian regions. SARS-CoV-2 RBD-specific antibodies were detected in 111 of 959 (11.6%) individuals, starting from September 2019 (14%), with a cluster of positive cases (>30%) in the second week of February 2020 and the highest number (53.2%) in Lombardy. This study shows an unexpected very early circulation of SARS-CoV-2 among asymptomatic individuals in Italy several months before the first patient was identified, and clarifies the onset and spread of the coronavirus disease 2019 (COVID-19) pandemic. Finding SARS-CoV-2 antibodies in asymptomatic people before the COVID-19 outbreak in Italy may reshape the history of pandemic

A peptide derived from TIMP-3 inhibits multiple angiogenic growth factor receptors and tumour growth and inflammatory arthritis in mice

The binding of vascular endothelial growth factor (VEGF) to VEGF receptor-2 (VEGFR-2) on the surface of vascular endothelial cells stimulates many steps in the angiogenic pathway. Inhibition of this interaction is proving of value in moderating the neovascularization accompanying age-related macular degeneration and in the treatment of cancer. Tissue inhibitor of metalloproteinases-3 (TIMP-3) has been shown to be a natural VEGFR-2 specific antagonist—an activity that is independent of its ability to inhibit metalloproteinases. In this investigation we localize this activity to the C-terminal domain of the TIMP-3 molecule and characterize a short peptide, corresponding to part of this domain, that not only inhibits all three VEGF-family receptors, but also fibroblast growth factor and platelet-derived growth factor receptors. This multiple-receptor inhibition may explain why the peptide was also seen to be a powerful inhibitor of tumour growth and also a partial inhibitor of arthritic joint inflammation in vivo

Экспериментальное изучение влияния глюкозамина гидрохлорида на развитие патоспермии стареющих крыс, вызванной доксорубицином

ГЛЮКОЗАМИНА ГИДРОХЛОРИДДОКСОРУБИЦИНПАТОСПЕРМИЯСТАРЕНИЕФАРМАКОЛОГИЯ КЛИНИЧЕСКАЯЛЕКАРСТВ ФИЗИОЛОГИЧЕСКОЕ ДЕЙСТВИЕРЕПРОДУКЦИЮ КОНТРОЛИРУЮЩИЕ СРЕДСТВАЭКСПЕРИМЕНТЫ НА ЖИВОТНЫХКРЫСЫЦель работы - исследование влияния глюкозамина гидрохлорида на развитие гипофункции семенников крыс, вызванной длительным введением доксорубицина на фоне старения животных

The lived experiences of Syrian Forced Migrants in the United Kingdom and the Implications for Clinical Interventions

The Syrian conflict, which broke out in 2011, has led to a rise in the number of Syrians seeking refuge in the United Kingdom (Karyotis et al., 2021). At the time of this study, approximately 20,000 Syrians have been resettled under Vulnerable Persons Resettlement Scheme (UK Parliament, 2019) and a further, 21,168 Syrians have been granted refugee status between (Migration Observatory, 2022). A review of the existing psychological literature shows that there has been scholarly interest in Syrian migrants (Tinghog et al., 2017; Cantekin & Gencoz, 2017), but very few of these studies are concerned with understanding Syrians’ perceptions and interpretations of their resettlement experiences. In light of this identified gap, the present study aimed to explore the subjective experiences of six forced Syrian migrants in the UK and their coping methods. Semi-structured interviews were conducted with each participant and transcribed. Transcripts were then analysed using Smith et al.’s (2019) a step-by-step guide to Interpretative Phenomenological Analysis (IPA). Four superordinate themes emerged through the analytical process: (1) Thrown in the deep end: the initial changes and challenges of being in the UK, (2) Tensions with identity and self- construal, (3) The ongoing search for belonging: facets of a home, and (4) Means of coping. These findings have been contextualised within the existing literature and their implications for clinical practice and policy have been discussed. Finally, the limitations of the current study and subsequent recommendations for future research have been proposed

Implementation Assessment of Executive Order 13518: The Veterans Employment Initiative (Executive Summary)

This is the Executive Summary of a report which documents the results of a year-long, independent study to assess the policy implementation of the government’s Veterans Employment Initiative (VEI). The study considers the initiative’s efficacy and impact, identifies successful practices, strategies and opportunities for improvement. This assessment also offers recommendations to senior policymakers and agency leaders on how to best position the VEI for future success