Reconstitution of Human Cytomegalovirus-Specific CD4+ T Cells is Critical for Control of Virus Reactivation in Hematopoietic Stem Cell Transplant Recipients but Does Not Prevent Organ Infection

The relative contribution of human cytomegalovirus (HMCV)-specific CD4(+) and CD8(+) T cells to the control of HCMV infection in hematopoietic stem cell transplant (HSCT) recipients is still controversial. HCMV reactivation and HCMV-specific CD4(+) and CD8(+) T cell reconstitution were monitored for 1 year in 63 HCMV-seropositive patients receiving HSCT. HCMV reactivation was detected in all but 2 patients. In 20 of 63 (31.7%) patients (group 1) HCMV infection resolved spontaneously, whereas 32 of 63 (50.8%) patients (group 2) controlled the infection after a single short-course of pre-emptive therapy and the remaining 9 (14.3%) patients (group 3) suffered from relapsing episodes of HCMV infection, requiring multiple courses of antiviral therapy. The kinetics and magnitude of HCMV-specific CD8(+) T cell reconstitution were comparable among the 3 groups, but HCMV-specific CD4(+) T cells were lower in number in patients requiring antiviral treatment. HCMV-seronegative donors, as well as unrelated donors (receiving antithymocyte globulin) and acute graft-versus-host disease (GVHD) were associated with both delayed HCMV-specific CD4(+) T cell reconstitution and severity of infection. Conversely, these risk factors had no impact on HCMV-specific CD8(+) T cells. Eight patients with previous GVHD suffered from HCMV gastrointestinal disease, although in the presence of HCMV-specific CD4(+) and CD8(+) systemic immunity and undetectable HCMV DNA in blood. Reconstitution of systemic HCMV-specific CD4(+) T cell immunity is required for control of HCMV reactivation in adult HSCT recipients, but it may not be sufficient to prevent late-onset organ localization in patients with GVHD. HCMV-specific CD8(+) T cells contribute to control of HCMV infection, but only after HCMV-specific CD4(+) T cell reconstitution

Refining virtual cross-national research collaboration : drivers, affordances and constraints

Publisher Copyright: © 2022, Irina A. Lokhtina, Laura Colombo, Citra Amelia, Erika Löfström, Anu Tammeleht, Anna Sala-Bubare, Marian Jazvac-Martek, Montserrat Castelló and Lynn McAlpine.Purpose: The study aims to explore and explain the affordances and constraints of two-mode virtual collaboration as experienced by a newly forming international research team. Design/methodology/approach: This is self-reflective and action-oriented research on the affordances and constraints of two-mode virtual collaboration. In the spirit of professional development, the authors (nine researchers at different career stages and from various counties) engaged in a joint endeavour to evaluate the affordances and constraints of virtual collaborations in light of the recent literature while also researching the authors' own virtual collaboration during this evaluative task (mid-January–April 2021). The authors used two modes: synchronous (Zoom) and asynchronous (emails) to communicate on the literature exploration and recorded reactions and emotional responses towards existing affordances and constraints through a collective journal. Findings: The results suggest both affordances in terms of communication being negotiable and evolving and constraints, particularly in forming new relations given tools that may not be equally accessible to all. Journaling during collaborations could be a valuable tool, especially for virtual collective work, because it can be used to structure the team supported negotiation and discussion processes, especially often hidden processes. It is evident that the role of a leader can contribute to an alignment in the assumptions and experiences of trust and consequently foster greater mutual understanding of the circumstances for productive team collaborations. Originality/value: The findings of this study can inform academics and practitioners on how to create and facilitate better opportunities for collaboration in virtual teams as a rapidly emerging form of technology-supported working.Peer reviewe

Refining virtual cross-national research collaboration : drivers, affordances and constraints

Publisher Copyright: © 2022, Irina A. Lokhtina, Laura Colombo, Citra Amelia, Erika Löfström, Anu Tammeleht, Anna Sala-Bubare, Marian Jazvac-Martek, Montserrat Castelló and Lynn McAlpine.Purpose: The study aims to explore and explain the affordances and constraints of two-mode virtual collaboration as experienced by a newly forming international research team. Design/methodology/approach: This is self-reflective and action-oriented research on the affordances and constraints of two-mode virtual collaboration. In the spirit of professional development, the authors (nine researchers at different career stages and from various counties) engaged in a joint endeavour to evaluate the affordances and constraints of virtual collaborations in light of the recent literature while also researching the authors' own virtual collaboration during this evaluative task (mid-January–April 2021). The authors used two modes: synchronous (Zoom) and asynchronous (emails) to communicate on the literature exploration and recorded reactions and emotional responses towards existing affordances and constraints through a collective journal. Findings: The results suggest both affordances in terms of communication being negotiable and evolving and constraints, particularly in forming new relations given tools that may not be equally accessible to all. Journaling during collaborations could be a valuable tool, especially for virtual collective work, because it can be used to structure the team supported negotiation and discussion processes, especially often hidden processes. It is evident that the role of a leader can contribute to an alignment in the assumptions and experiences of trust and consequently foster greater mutual understanding of the circumstances for productive team collaborations. Originality/value: The findings of this study can inform academics and practitioners on how to create and facilitate better opportunities for collaboration in virtual teams as a rapidly emerging form of technology-supported working.Peer reviewe

Phenotypic spectrum and transcriptomic profile associated with germline variants in TRAF7

PURPOSE: Somatic variants in tumor necrosis factor receptor-associated factor 7 (TRAF7) cause meningioma, while germline variants have recently been identified in seven patients with developmental delay and cardiac, facial, and digital anomalies. We aimed to define the clinical and mutational spectrum associated with TRAF7 germline variants in a large series of patients, and to determine the molecular effects of the variants through transcriptomic analysis of patient fibroblasts. METHODS: We performed exome, targeted capture, and Sanger sequencing of patients with undiagnosed developmental disorders, in multiple independent diagnostic or research centers. Phenotypic and mutational comparisons were facilitated through data exchange platforms. Whole-transcriptome sequencing was performed on RNA from patient- and control-derived fibroblasts. RESULTS: We identified heterozygous missense variants in TRAF7 as the cause of a developmental delay-malformation syndrome in 45 patients. Major features include a recognizable facial gestalt (characterized in particular by blepharophimosis), short neck, pectus carinatum, digital deviations, and patent ductus arteriosus. Almost all variants occur in the WD40 repeats and most are recurrent. Several differentially expressed genes were identified in patient fibroblasts. CONCLUSION: We provide the first large-scale analysis of the clinical and mutational spectrum associated with the TRAF7 developmental syndrome, and we shed light on its molecular etiology through transcriptome studies

Search for dark matter produced in association with bottom or top quarks in √s = 13 TeV pp collisions with the ATLAS detector

A search for weakly interacting massive particle dark matter produced in association with bottom or top quarks is presented. Final states containing third-generation quarks and miss- ing transverse momentum are considered. The analysis uses 36.1 fb−1 of proton–proton collision data recorded by the ATLAS experiment at √s = 13 TeV in 2015 and 2016. No significant excess of events above the estimated backgrounds is observed. The results are in- terpreted in the framework of simplified models of spin-0 dark-matter mediators. For colour- neutral spin-0 mediators produced in association with top quarks and decaying into a pair of dark-matter particles, mediator masses below 50 GeV are excluded assuming a dark-matter candidate mass of 1 GeV and unitary couplings. For scalar and pseudoscalar mediators produced in association with bottom quarks, the search sets limits on the production cross- section of 300 times the predicted rate for mediators with masses between 10 and 50 GeV and assuming a dark-matter mass of 1 GeV and unitary coupling. Constraints on colour- charged scalar simplified models are also presented. Assuming a dark-matter particle mass of 35 GeV, mediator particles with mass below 1.1 TeV are excluded for couplings yielding a dark-matter relic density consistent with measurements