A comprehensive analysis of cell-autonomous and non-cell-autonomous regulation of myeloid leukemic cells: The prospect of developing novel niche-targeting therapies.

Leukemic cells (LCs) arise from the hematopoietic stem/and progenitor cells (HSCs/HSPCs) and utilize cues from the bone marrow microenvironment (BMM) for their regulation in the same way as their normal HSC counterparts. Mesenchymal stromal cells (MSCs), a vital component of the BMM promote leukemogenesis by creating a protective and immune-tolerant microenvironment that can support the survival of LCs, helping them escape chemotherapy, thereby resulting in the relapse of leukemia. Conversely, MSCs also induce apoptosis in the LCs and inhibit their proliferation by interfering with their self-renewal potential. This review discusses the work done so far on cell-autonomous (intrinsic) and MSCs-mediated non-cell-autonomous (extrinsic) regulation of myeloid leukemia with a special focus on the need to investigate the extrinsic regulation of myeloid leukemia to understand the contrasting role of MSCs in leukemogenesis. These mechanisms could be exploited to formulate novel therapeutic strategies that specifically target the leukemic microenvironment.

Overlapping research efforts in a global pandemic: a rapid systematic review of COVID-19-related individual participant data meta-analyses.

BACKGROUND: Individual participant data meta-analyses (IPD-MAs), which involve harmonising and analysing participant-level data from related studies, provide several advantages over aggregate data meta-analyses, which pool study-level findings. IPD-MAs are especially important for building and evaluating diagnostic and prognostic models, making them an important tool for informing the research and public health responses to COVID-19. METHODS: We conducted a rapid systematic review of protocols and publications from planned, ongoing, or completed COVID-19-related IPD-MAs to identify areas of overlap and maximise data request and harmonisation efforts. We searched four databases using a combination of text and MeSH terms. Two independent reviewers determined eligibility at the title-abstract and full-text stages. Data were extracted by one reviewer into a pretested data extraction form and subsequently reviewed by a second reviewer. Data were analysed using a narrative synthesis approach. A formal risk of bias assessment was not conducted. RESULTS: We identified 31 COVID-19-related IPD-MAs, including five living IPD-MAs and ten IPD-MAs that limited their inference to published data (e.g., case reports). We found overlap in study designs, populations, exposures, and outcomes of interest. For example, 26 IPD-MAs included RCTs; 17 IPD-MAs were limited to hospitalised patients. Sixteen IPD-MAs focused on evaluating medical treatments, including six IPD-MAs for antivirals, four on antibodies, and two that evaluated convalescent plasma. CONCLUSIONS: Collaboration across related IPD-MAs can leverage limited resources and expertise by expediting the creation of cross-study participant-level data datasets, which can, in turn, fast-track evidence synthesis for the improved diagnosis and treatment of COVID-19. TRIAL REGISTRATION: 10.17605/OSF.IO/93GF2.

CO2 Absorption Using Hollow Fiber Membrane Contactors: Introducing pH Swing Absorption (pHSA) to Overcome Purity Limitation.

Recently, membrane contactors have gained more popularity in the field of CO2 removal; however, achieving high purity and competitive recovery for poor soluble gas (H2, N2, or CH4) remains elusive. Hence, a novel process for CO2 removal from a mixture of gases using hollow fiber membrane contactors is investigated theoretically and experimentally. A theoretical model is constructed to show that the dissolved residual CO2 hinders the capacity of the absorbent when it is regenerated. This model, backed up by experimental investigation, proves that achieving a purity > 99% without consuming excessive chemicals or energy remains challenging in a closed-loop system. As a solution, a novel strategy is proposed: the pH Swing Absorption which consists of manipulating the acido-basic equilibrium of CO2 in the absorption and desorption stages by injecting moderate acid and base amount. It aims at decreasing CO2 residual content in the regenerated absorbent, by converting CO2 into its ionic counterparts (HCO3- or CO32-) before absorption and improving CO2 degassing before desorption. Therefore, this strategy unlocks the theoretical limitation due to equilibrium with CO2 residual content in the absorbent and increases considerably the maximum achievable purity. Results also show the dependency of the performance on operating conditions such as total gas pressure and liquid flowrate. For N2/CO2 mixture, this process achieved a nitrogen purity of 99.97% with a N2 recovery rate of 94.13%. Similarly, for H2/CO2 mixture, a maximum H2 purity of 99.96% and recovery rate of 93.96% was obtained using this process. Moreover, the proposed patented process could potentially reduce energy or chemicals consumption.

Guidance for ensuring fair and ethical broad consent for future use. A scoping review protocol.

Introduction: Broad consent for future use is the reuse of data and/or samples collected by a study by researchers who may not be affiliated with the original study team for purposes that may differ from the objectives of the original study. Sharing participant-level data and samples collected from research participants facilitates reuse and transparency and can accelerate drug or vaccine development, research findings, and translation. Data reuse and synthesis help prevent unnecessary research, thereby respecting research participants time and efforts and building their trust in the research process. Despite these myriad benefits, data and sample sharing represent a significant investment of time for the team that collected the data or samples, and may present additional risks for research participants, including that of re-identifiability and incidental findings, or for the source community. This scoping review will summarize existing guidance on broad consent for future use and highlight evidence gaps related to the ethical, equitable implementation of broad consent for future use. Methods and analysis: We will apply the Arskey and O'Malley scoping review methodology and best practice as outlined in the Joanna Briggs scoping review guidelines.  The research questions have been identified through a literature review and consultation with subject-matter experts. The systematic search will be conducted in three databases using a tailored search strategy. We will search the reference lists of included articles or related systematic reviews for additional citations. The title-abstract and full text screening and charting the data will be conducted independently by two reviewers. Discrepancies will be resolved by a third reviewer. Results will be summarized in narrative form. Ethics and dissemination: This scoping review summarizes findings from existing publications and grey literature rather than primary data and, as such, does not require ethics review. Findings will be disseminated through an open access publication and webinar.