Centre Virchow-Villermé

A common misconception that prevails within some research communities postulates that research results 'speak for themselves' and are thus sufficient to influence policy. Yet, high-fidelity uptake of research is rarely a passive process; more often, researchers need to actively engage with policymakers. This process of policy engagement strives towards producing robust science that contributes to the betterment of our societies-but it is a process for which many researchers are not adequately trained. If publicly funded research fails to influence policy, many would regard it as falling short of fulfilling its potential value to society. Herein, we provide a framework for research-policymaker engagement, framed around the questions of why, on what, with whom, when, where and how clinical and public-health researchers can and should undertake engagement with policymakers. The views presented in this Perspective are a synthesis of the diverse, collective experience of the authors across global health contexts, supported by real-world illustrative case studies. We provide tangible recommendations for researchers, funders and policymakers to facilitate bridging the gap between evidence and policy.

• Well-watered trees reduced UTCI from 5.8°C at mid-May to 7.9°C in late August. • An 8-week moderate water restriction decreased thermal comfort by up to 2.7°C UTCI. • Thermal comfort improvement mainly relied on shading effects in all conditions. • LAI above a threshold ensured high interception; larger crowns further improved UTCI. • Drought reduced thermal benefits by altering tree architecture and decreasing LAI. Street trees have gained attention for improving thermal comfort in cities, yet seasonal changes in tree services in relation to the evolution of tree architecture are not well understood. This study hypothesizes that over a growing season and for sunny days, changes in climate services primarily rely on tree architecture influence on cast-shadow, especially during summer droughts. Two alignments of ornamental apple trees were grown in a reduced-scale street canyon, with a non-vegetated control zone. All trees were well watered until July 5th, 2022, after which one alignment experienced moderate water restriction while the other remained well-watered. The street microclimate was characterized, the universal thermal climate index (UTCI) calculated, and tree architecture at the organ and crown scales was measured. On sunny days, well-watered trees improved thermal comfort from 5.8°C UTCI in mid-May to 7.9°C in late August, while water restriction reduced this benefit by up to 2.7°C UTCI after 8 weeks. The changes in thermal comfort were primarily linked to tree architectural development and cast-shadow, although these effects were moderate due to leaf area index high enough in May to ensure 87.5 % of interception of radiation. Increases in crown projected area and volume enhanced tree services, with larger effects on the side than just below the tree canopy. Water restriction diminished thermal comfort by inhibiting stem growth and accelerating leaf fall, thus reducing light interception. This study highlights the significant role of architectural plasticity in tree climate services under water restriction, warranting further research in other species.

H. Ghesquières and C. Thieblemont equally contributing author. Introduction: Marginal zone lymphomas (MZL) are traditionally categorized into three subtypes: extranodal (EMZL), splenic (SMZL), and nodal (NMZL). Current histological classifications (ICC and WHO) identify monoclonal B-cell lymphocytosis of MZL type (MBL-MZ) as a precursor state, and separate cutaneous MZL as a distinct entity—but fail to provide a clinically relevant classification integrating all disease sites. The FIL NF10 study proposed a fourth subtype—disseminated MZL—encompassing biologically diverse conditions. To refine MZL classification, we developed RECLASS, an algorithm-based system harmonizing histological and clinical criteria. Methods: The RECLASS system acknowledges MBL-MZ (i.e., lymphocytosis ± bone marrow involvement, in the absence of lymphadenopathy or any organ involvement) and primary cutaneous MZL (i.e., with no evidence of extracutaneous disease) as distinct entities and disregards blood and bone marrow involvement in subtyping. Classification follows these hierarchical rules: (1) If any mucosal site is involved: EMZL; (2) If no mucosal site is involved and spleen is involved (enlargement or focal lesion): SMZL; (3) If neither condition is met: NMZL. Leveraging data from the REALYSA French prospective cohort (all MZL cases between 12/2018 and 12/2022), we analyzed subtype distribution and disease dissemination according to (a) treating physicians from the REALYSA database (i.e., as per WHO2016 classification), (b) the FIL and (c) the RECLASS classifying and staging system. Results: Among 302 patients, the number of EMZL cases varied across classifications (140 physicians/WHO2016 versus 109 FIL vs. 175 RECLASS). FIL's unique “disseminated” category (115 patients) was reclassified within EMZL, SMZL, or NMZL under RECLASS. Therefore, SMZL cases increased under RECLASS (40 FIL vs. 67 RECLASS), as did NMZL cases (46 FIL vs. 56 RECLASS). RECLASS identified only one case of primary cutaneous MZL and 11 of MBL-MZ—these subtypes not being managed by hematologists unless systemic therapy is needed. Dissemination was reported in 219 (73%) cases by local physicians, but only in 113 (FIL, 37%) and 94 (RECLASS, 31%) patients based on structured classification. All 14 patients with ENT involvement were classified as EMZL in RECLASS, and were localized disease. Conclusion: RECLASS introduces a refined classification system for MZL, aligning with histological criteria while improving clinical relevance. Validation in independent international cohorts is ongoing. Research funding declaration: LYSARC—data collection, data quality check and data management Keywords: pathology and classification of lymphomas; extranodal non-Hodgkin lymphoma; indolent non-Hodgkin lymphoma No potential sources of conflict of interest.

Background Digital repositories and databases facilitate faster dissemination, transparency, and stakeholder collaboration. This review aimed to map and evaluate such digital infrastructures, focusing on their scope, content, functionality, adherence to FAIR (Findability, Accessibility, Interoperability and Reuse) principles, and user interface and experiences (UI/UX). Methods A review of global digital health policy repositories was conducted across multiple search engines and databases. The review targeted digital repositories that systematically collate health policy documents at a global level. Two country-specific repositories with a bearing on global health policies were also included. Results The study identified 59 global health policy repositories, with 15 matching our inclusion criteria evaluated in detail. These repositories contain vast amounts of data and are generally freely accessible, rendering them immensely rich sources for health policy documents, though with significant variability in content and coverage. The majority have a health focus, including HIV/AIDS, non-communicable diseases (NCDs), and maternal, newborn, and child health (MNCH); about a third are more broad and emerging health threats are often neglected. Accessibility and usability are limited, with basic user interface features such as search and filtering tools are present for almost all repositories and a notable lack of advanced analytics or artificial intelligence capabilities. Furthermore, many repositories struggle to adhere to FAIR principles, reducing their utility and potential for integration. Sustainability is also a concern, as funding often relies on short-term projects or philanthropic support, undermining long-term viability. Conclusion These issues collectively hinder the ability of digital health policy repositories to support comprehensive and timely global health policy development. To unlock the full potential of existing or new repositories for health policy, identified challenges should be tackled systematically. We provide specific recommendations aimed at driving the development of equitable, inclusive, high-functioning repositories and strengthening evidence-driven global health policy systems.

SummaryPeople with HIV are up to 100 times more likely to develop anal carcinoma compared to the general population. Diagnosing and treating precursor lesions, specifically high‐grade anal dysplasia, can significantly reduce the risk of developing anal carcinoma. This S2k‐guideline outlines the factors that increase the likelihood of developing anal carcinoma and its precursors, including advancing age, a low CD4+ T‐lymphocyte nadir, active cigarette smoking, receptive anal intercourse, or persistent infection with high‐risk (HR) types of human papillomavirus (HPV). Screening is primarily recommended for all men who have sex with men (MSM) and transgender women with HIV starting at age 35, and all people with HIV starting at age 45.After inspection and digital anorectal examination, anal cytology is collected. An HR‐HPV test may be performed. If clinical abnormalities are present or if cytology shows “ASC‐US or worse”, a referral for high‐resolution anoscopy (HRA) is indicated. If lesions are found during HRA, a biopsy should be obtained. Anal intraepithelial neoplasia (AIN) grade‐III or AIN‐II p16‐positive correspond to high‐grade dysplasia and require treatment. The most strongly recommended therapeutic options are electrocautery, 85% trichloroacetic acid, and surgical excision.Finally, the guideline discusses how these screening recommendations can be applied to individuals without HIV.

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The potential prognostic influence of genetic aberrations on chronic lymphocytic leukaemia (CLL) can vary based on various factors, such as the immunoglobulin heavy variable (IGHV) status. We conducted an integrative analysis on genetic abnormalities identified through cytogenetics and targeted next-generation sequencing in 536 CLL patients receiving first-line chemo(immuno)therapies (CIT) as part of two prospective trials. We evaluated the prognostic implications of the main abnormalities, with specific attention to their relative impact according to IGHV status. In the entire cohort, unmutated (UM)-IGHV, complex karyotype, del(11q) and ATM mutations correlated significantly with shorter progression-free survival (PFS). Focusing on the subset of mutated IGHV (M-IGHV) patients, univariate analysis showed that complex karyotype, del(11q), SF3B1 and SAMHD1 mutations were associated with significant lower PFS. The prognostic influence varied based on the patient's IGHV status, as these abnormalities did not affect outcomes in the UM-IGHV subgroup. TP53 mutations had no significant impact on outcomes in the M-IGHV subgroup. Our findings highlight the diverse prognostic influence of genetic aberrations depending on the IGHV status in symptomatic CLL patients receiving first-line CIT. The prognosis of gene mutations and cytogenetic abnormalities needs to be investigated with a compartmentalized methodology, taking into account the IGVH status of patients receiving first-line BTK and/or BCL2 inhibitors.