Safety and Activity of PolyPEPI1018 Combined with Maintenance Therapy in Metastatic Colorectal Cancer: an Open-Label, Multicenter, Phase Ib Study

Purpose: Although chemotherapy is standard of care for met- astatic colorectal cancer (mCRC), immunotherapy has no role in microsatellite stable (MSS) mCRC, a “cold” tumor. PolyPEPI1018 is an off-the-shelf, multi-peptide vaccine derived from 7 tumor- associated antigens (TAA) frequently expressed in mCRC. This study assessed PolyPEPI1018 combined with first-line maintenance therapy in patients with MSS mCRC. Patients and Methods: Eleven patients with MSS mCRC received PolyPEPI1018 and Montanide ISA51VG adjuvant subcutaneously, combined with fluoropyrimidine/biologic follow- ing first-line induction with chemotherapy and a biologic (NCT03391232). In Part A of the study, 5 patients received a single dose; in Part B, 6 patients received up to three doses of Poly- PEPI1018 every 12 weeks. The primary objective was safety; sec- ondary objectives were preliminary efficacy, immunogenicity at peripheral and tumor level, and immune correlates. Results: PolyPEPI1018 vaccination was safe and well tolerated. No vaccine-related serious adverse event occurred. Eighty percent of patients had CD8þ T-cell responses against ≥3 TAAs. Increased density of tumor-infiltrating lymphocytes were detected post- treatment for 3 of 4 patients’ liver biopsies, combined with increased expression of immune-related gene signatures. Three patients had objective response according to RECISTv1.1, and 2 patients qual- ified for curative surgery. Longer median progression-free survival for patients receiving multiple doses compared with a single dose (12.5 vs. 4.6 months; P 1⁄4 0.017) suggested a dose–efficacy correlation. The host HLA genotype predicted multi-antigen– specific T-cell responses (P 1⁄4 0.01) indicative of clinical outcome. Conclusions: PolyPEPI1018 added to maintenance chemother- apy for patients with unresectable, MSS mCRC was safe and associated with specific immune responses and antitumor activity warranting further confirmation in a randomized, controlled setting

Minimal information for studies of extracellular vesicles (MISEV2023): From basic to advanced approaches

Extracellular vesicles (EVs), through their complex cargo, can reflect the state of their cell of origin and change the functions and phenotypes of other cells. These features indicate strong biomarker and therapeutic potential and have generated broad interest, as evidenced by the steady year-on-year increase in the numbers of scientific publications about EVs. Important advances have been made in EV metrology and in understanding and applying EV biology. However, hurdles remain to realising the potential of EVs in domains ranging from basic biology to clinical applications due to challenges in EV nomenclature, separation from non-vesicular extracellular particles, characterisation and functional studies. To address the challenges and opportunities in this rapidly evolving field, the International Society for Extracellular Vesicles (ISEV) updates its 'Minimal Information for Studies of Extracellular Vesicles', which was first published in 2014 and then in 2018 as MISEV2014 and MISEV2018, respectively. The goal of the current document, MISEV2023, is to provide researchers with an updated snapshot of available approaches and their advantages and limitations for production, separation and characterisation of EVs from multiple sources, including cell culture, body fluids and solid tissues. In addition to presenting the latest state of the art in basic principles of EV research, this document also covers advanced techniques and approaches that are currently expanding the boundaries of the field. MISEV2023 also includes new sections on EV release and uptake and a brief discussion of in vivo approaches to study EVs. Compiling feedback from ISEV expert task forces and more than 1000 researchers, this document conveys the current state of EV research to facilitate robust scientific discoveries and move the field forward even more rapidly

Self-determined profiles of academic motivation

This study was designed to investigate academic motivation profiles (and their similarity) among distinct samples of high school students. Anchored in recent developments in Self-Determination Theory, these profiles were estimated while considering both the global and specific nature of academic motivation. The role of fixed mindsets and parenting practices in predicting profile membership, as well as the implications of these profiles for several outcomes, were also investigated. Latent profile analysis revealed five profiles (Weakly Motivated, Moderately Motivated, Self-Determined, Amotivated, and Strongly Motivated) differing in global and specific motivation levels. Fixed mindset was weakly related to profile membership, perceived parenting practices showed more widespread associations. Most desirable outcomes were linked to the Self-Determined and Strongly Motivated profiles, and then to the Moderately Motivated, Weakly Motivated, and Amotivated profiles

Structure of sputtered nanocomposite CrC[sub x]∕a-C:H thin films

This work presents the structural evolution of nanocomposite CrCx∕a-C:H coatings prepared by unbalanced magnetron sputtering of a metallic Cr target in Ar+CH4 glow discharges using low negative dc bias voltages. Raman spectroscopy and x-ray photoelectron spectroscopy were used to characterize the phase composition and the chemical bonding in the films deposited at different experimental conditions. The results were correlated to the chemical composition obtained by elastic recoil detection analysis. The coating microstructure was investigated on selected samples by high-resolution transmission electron microscopy combined with electron energy-loss spectroscopy analysis. The nanocomposite coatings can be divided into hard CrCx dominated films, when prepared at low CH4 partial pressure to total pressure (pt) ratios (pCH4/pt0.4. The structure of the low-friction a-C:H dominated coatings consists of 2–10nm sized fcc CrC crystallites embedded in a Cr containing a-C:H matrix

Nuclear Safety Research Support Facilities for Existing and Advanced Reactors: 2021 Update

At its 61st meeting in June 2017, the Nuclear Energy Agency (NEA) Committee on the Safety of Nuclear Installations (CSNI) decided to establish a Senior Expert Group on Safety Research (SESAR) to update previous assessments of capabilities and facilities required to support the safety of nuclear installations. The NEA issued a report on this activity in 2001 entitled Nuclear Safety Research in OECD Countries: Major Facilities and Programmes at Risk. Six years later, a followon activity resulted in the publication SESAR/SFEAR: Nuclear Safety Research in OECD Countries – Support Facilities for Existing and Advanced Reactors (2007). The SESAR/SFEAR2’s mandate is as follows: “The Senior Expert Group on Safety Research/ Support Facilities for Existing and Advanced Reactors 2 (SESAR/SFEAR2) is responsible for reviewing and updating the previous SESAR assessments of research facilities required to support the safety of nuclear installations. The group shall recommend actions to be taken by the CSNI and its member countries to facilitate broader use and sustained operation of essential research facilities required to support nuclear safety.” The activity described in this report builds upon and updates the previous work, expanding its scope to cover advanced reactors, including evaluations performed by the Task Group on Advanced Reactor Experimental Facilities (TAREF) and the emergence of several proposed molten salt and small modular reactor designs. In addition, although the need to maintain experimental databases was recognised as an important issue, it was not treated specifically in previous reports; the present report therefore makes some direct recommendations regarding database maintenance