Robust SARS-CoV-2 T cell responses with common TCR?? motifs toward COVID-19 vaccines in patients with hematological malignancy impacting B cells

Immunocompromised hematology patients are vulnerable to severe COVID-19 and respond poorly to vaccination. Relative deficits in immunity are, however, unclear, especially after 3 vaccine doses. We evaluated immune responses in hematology patients across three COVID-19 vaccination doses. Seropositivity was low after a first dose of BNT162b2 and ChAdOx1 (∼26%), increased to 59%–75% after a second dose, and increased to 85% after a third dose. While prototypical antibody-secreting cells (ASCs) and T follicular helper (Tfh) cell responses were elicited in healthy participants, hematology patients showed prolonged ASCs and skewed Tfh2/17 responses. Importantly, vaccine-induced expansions of spike-specific and peptide-HLA tetramer-specific CD4+/CD8+ T cells, together with their T cell receptor (TCR) repertoires, were robust in hematology patients, irrespective of B cell numbers, and comparable to healthy participants. Vaccinated patients with breakthrough infections developed higher antibody responses, while T cell responses were comparable to healthy groups. COVID-19 vaccination induces robust T cell immunity in hematology patients of varying diseases and treatments irrespective of B cell numbers and antibody response

Fossil seamount in southeast Zagros records intraoceanic arc to back-arc transition: New constraints for the evolution of the Neotethys

International audienceThe Neotethys ocean is transiently involved in two subduction zones during the Late Cretaceous. While the Northern Neotethys subduction zone (below Eurasia) was active from the early Mesozoic until the Eocene, the intra-oceanic Southern Neotethys subduction zone only developed during the Late Cretaceous. We herein document, through a combination of structural, geochemical and geochronological data, the magmatic evolution of a Late Cretaceous supra-subduction ophiolite fragment of the Neotethys (the Siah Kuh massif, Southern Iran), now sandwiched in the Zagros suture zone. Results show that this ophiolite fragment — a subducted yet exceptionally well-preserved seamount — records an evolution from supra-subduction zone magmatism (including island arc tholeiites, boninites and calc-alkaline transitional magmatism) around 87 Ma, to MORB (from E-MORB to N-MORB) magmatism at 78 Ma, and potentially until 73 Ma. We conclude that this seamount initially formed in an arc context and represents either (i) a non-obducted remnant of the Oman ophiolite that experienced a longer-lived magmatic history (prefered hypothesis) or (ii) a piece from the forearc/frontal arc of the Northern margin of the Neotethys. Regardless of its exact original location, the Siah Kuh seamount was later subducted in the Northern Neotethys subduction zone

Tectonic slicing and mixing processes along the subduction interface: The Sistan example (Eastern Iran)

International audienceSuture zones preserve metamorphosed relicts of subducted ocean floor later exhumed along the plate interface that can provide critical insights on subduction zone processes. Mélange-like units are exceptionally well-exposed in the Sistan suture (Eastern Iran), which results from the closure of a branch of the Neotethys between the Lut and Afghan continental blocks. High pressure rocks found in the inner part of the suture zone (i.e., Ratuk complex) around Gazik are herein compared to previously studied outcrops along the belt. Detailed field investigations and mapping allow the distinction of two kinds of subduction-related block-in-matrix units: a siliciclastic-matrix complex and a serpentinite-matrix complex. The siliciclastic-matrix complex includes barely metamorphosed blocks of serpentinized peridotite, radiolarite and basalt of maximum greenschist-facies grade (i.e., maximum temperature of 340 °C). The serpentinite-matrix complex includes blocks of various grades and lithologies: mafic eclogites, amphibolitized blueschists, blue-amphibole-bearing metacherts and aegirine-augite-albite rocks. Eclogites reached peak pressure conditions around 530 °C and 2.3 GPa and isothermal retrogression down to 530 °C and 0.9 GPa. Estimation of peak PT conditions for the other rocks are less-well constrained but suggest equilibration at P < 1 GPa. Strikingly similar Ar–Ar ages of 86 ± 3 Ma, along ~70 km, are obtained for phengite and amphibole from fourteen eclogite and amphibolitized blueschist blocks. Ages in Gazik are usually younger than further south (e.g., Sulabest), but there is little age difference between the various kinds of rocks. These results (radiometric ages, observed structures and rock types) support a tectonic origin of the serpentinite-matrix mélange and shed light on subduction zone dynamics, particularly on coeval detachment and exhumation mechanisms of slab-derived rocks

Safety and adherence to medications and self-care advice in oncology (SAMSON): pilot randomised controlled trial protocol

INTRODUCTION: With the increasing use of oral anti-cancer medicines (OAMs), research demonstrating the magnitude of the medication non-adherence problem and its consequences on treatments' efficacy and toxicity is drawing more attention. Mobile phone interventions may be a practical solution to support patients taking OAMs at home, yet evidence to inform the efficacy of these interventions is lacking. The safety and adherence to medications and self-care advice in oncology (SAMSON) pilot randomised control trial (RCT) aims to evaluate the acceptability, feasibility and potential efficacy of a novel digital solution to improve medication adherence (MA) among people with cancer. METHODS AND ANALYSIS: This is a two-arm, 12-week, pilot RCT aiming to enrol 50 adults with haematological, lung or melanoma cancers at an Australian metropolitan specialised oncology hospital, who are taking oral anti-cancer medicines. Participants will be randomised (1:1 allocation ratio) to either the intervention group (SAMSON solution) or the control group (usual care). The primary outcomes are the acceptability and feasibility of SAMSON. The secondary outcomes are MA, toxicity self-management, anxiety and depressive symptoms, health-related quality of life, and parameters relating to optimal intervention strategy. Quantitative data will be analysed on a modified intention-to-treat basis. SUMMARY: While multicomponent interventions are increasingly introduced, SAMSON incorporates novel approaches to the solution. SAMSON provides a comprehensive, patient-centred, digital MA intervention solution with seamless integration of a mobile platform with clinical consultations that are evidence-based, theory-based, co-designed and rigorously tested. The pilot trial will determine whether this type of intervention is feasible and acceptable in oncology and will provide a foundation for a future full-scale RCT. ETHICS AND DISSEMINATION: Primary ethics approvals were received from Peter MacCallum Cancer Centre and Swinburne University of Technology Human Research Ethics Committees (HREC/95332/PMCC and 20237273-15836). Results will be disseminated via peer-reviewed publications and presentations at international and national conferences. TRIAL REGISTRATION NUMBER: The protocol has been prospectively registered on the Australian New Zealand Clinical Trials Registry with trial registration number (ACTRN12623000472673)