Institute of Child Health

Metastatic breast cancer cells disseminate to organs with a soft microenvironment. Whether and how the mechanical properties of the local tissue influence their response to treatment remains unclear. Here we found that a soft extracellular matrix empowers redox homeostasis. Cells cultured on a soft extracellular matrix display increased peri-mitochondrial F-actin, promoted by Spire1C and Arp2/3 nucleation factors, and increased DRP1- and MIEF1/2-dependent mitochondrial fission. Changes in mitochondrial dynamics lead to increased production of mitochondrial reactive oxygen species and activate the NRF2 antioxidant transcriptional response, including increased cystine uptake and glutathione metabolism. This retrograde response endows cells with resistance to oxidative stress and reactive oxygen species-dependent chemotherapy drugs. This is relevant in a mouse model of metastatic breast cancer cells dormant in the lung soft tissue, where inhibition of DRP1 and NRF2 restored cisplatin sensitivity and prevented disseminated cancer-cell awakening. We propose that targeting this mitochondrial dynamics- and redox-based mechanotransduction pathway could open avenues to prevent metastatic relapse.

Lupus nephritis (LN) is a severe manifestation of systemic lupus erythematosus (SLE), affecting up to one-third of pediatric SLE patients. Timely induction therapy is critical in proliferative LN to prevent progression to kidney failure or death. Intravenous cyclophosphamide (IVCP) has long been a standard induction agent, but its toxicity profile has prompted interest in mycophenolate mofetil (MMF) as a potentially safer alternative. However, data comparing the efficacy and safety of MMF versus IVCP in children are limited and inconclusive. To systematically review and synthesise existing evidence comparing the efficacy and safety of MMF versus IVCP for induction therapy in pediatric patients with proliferative LN. A comprehensive search was conducted in six electronic databases (PubMed, EMBASE, Web of Science, SCOPUS, CINAHL, and CENTRAL) on June 2, 2025. Reference lists of included articles were also manually screened. We included randomised controlled trials and observational studies published in English that directly compared MMF and IVCP as induction therapies in pediatric patients with biopsy-proven proliferative LN. Studies were required to report at least one of the following outcomes: kidney remission (complete or partial), adverse events, kidney failure, or death. Eligible participants were children aged ≤ 17 years with a diagnosis of proliferative LN based on the American College of Rheumatology (ACR) criteria. Interventions involved MMF plus corticosteroids versus IVCP plus corticosteroids, with comparable adjunctive therapies. Authors independently screened articles, extracted data, and assessed study quality using the RoB2 tool for RCTs and the ROBINS-I tool for observational studies. A random-effects meta-analysis was conducted to estimate pooled risk ratios (RRs) for complete remission. Sensitivity analyses and funnel plots were used to assess robustness and publication bias. Out of 1,633 screened records, seven studies met the inclusion criteria, six observational studies (n = 282) and one RCT (n = 24). Meta-analysis of the observational studies revealed no significant difference in complete remission between the MMF and IVCP groups (pooled RR: 1.01; 95 https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42024533313

Atopic dermatitis (AD) is a chronic inflammatory skin disease with significant morbidity. Recognising the need for region-specific guidance, the Skin Allergy Research Society and Society for Eczema Studies have collaborated to develop updated, evidence-based guidelines tailored to the Indian context. These guidelines address AD management across all age groups, special populations while considering local epidemiology, healthcare infrastructure, and treatment accessibility. A structured Delphi consensus process was conducted among 23 dermatology experts over 3 months through virtual and in-person meetings. Literature from MEDLINE, Cochrane, and Google Scholar was systematically reviewed, and the GRADE (Grading of Recommendations, Assessment, Development, and Evaluations) approach was used to assess evidence quality. Clinical recommendations were refined through multiple voting rounds, leading to consensus statements. Recommendations are based on an extensive literature review up to December 2024. This document updates the 2019 Skin Allergy Society guidelines, reinforcing global recommendations while allowing local adaptability. These guidelines provide updated recommendations for topical, systemic, phototherapy, and biologic therapies in AD. Key advancements include the introduction of topical crisaborole and JAK inhibitors for mild to moderate AD, along with a focus on emerging systemic therapies, such as biologics and systemic JAK inhibitors. In the Indian context, the guidelines define the roles of dupilumab and abrocitinib while also addressing the off-label use of tofacitinib and baricitinib in resource-limited settings. Specific recommendations are provided for children, elderly patients, and pregnant women, emphasising safety considerations for systemic and biologic therapies. These guidelines align with global AD management while incorporating India-specific adaptations based on epidemiology, accessibility, and affordability. They serve as a key reference for dermatologists, pediatricians, and general practitioners in India and other resource-limited settings. Though tailored for India, they are also relevant to dermatologists in developing countries, guiding treatment selection based on disease patterns, environmental factors, and medication availability.

PurposeThis study provides insight into the design, implementation and evaluation of a structured developmental mentoring programme, created to support the academic and professional development of postdoctoral researchers from diverse disciplines and backgrounds. The research context is the National Institute for Health and Care Research (NIHR) Academy. The Academy attracts, trains and supports health and care researchers through personal or institutional career development awards, as well as training and academic career development within NIHR infrastructure, schools and capacity-building structures. The mentoring programme is open to all UK-based postdoctoral Academy members.Design/methodology/approachThe approach first sets out the context, purpose and design of the mentoring programme. Second, we explore the extent to which the mentor- and mentee-defined relationship objectives were fulfilled and whether the programme met the underlying principles of the NIHR. Finally, we identified participants' level of satisfaction with the programme. The study adopted a pragmatic multiple-method evaluation, with matched-pair mentee and mentor interviews that were thematically analysed.FindingsThe study found that all participants felt they met all or most of their mentoring objectives and overall programme objectives. The mentoring programme was highly valued by a diverse range of participating mentors and mentees from different health, care and research disciplines, reflective of the NIHR Academy.Research limitations/implicationsLimitations of this study include the short-term outcomes that participants were asked to reflect on at the end of the one-year programme; other studies may capture longer-term outcomes through longitudinal evaluation.Originality/valueThe study contributes to the body of knowledge regarding the benefits and organisational support that postdoctoral researchers (mentees) and their mentors receive through mentoring programme participation. This study underscores the importance and impact of a structured, formal organisational mentoring programme.

This study aimed to develop consensus on a comprehensive and abridged list of recommendations for conducting antiracist research across all stages of a pediatric research project. Antiracist research aims to ensure that the construct of race is correctly interpreted and that racially and ethnically minoritized communities are fairly engaged throughout a research project. Using a modified Delphi approach, experts in equitable pediatric research methods completed 3 rounds of surveys and virtual focus groups between April and December 2023. Round 1 asked experts to add to or revise themes and subthemes gathered from a systematic review of published antiracist practices. Round 2 included ranking items’ importance; items voted in the top 50% by 60% of experts were included in an abridged list of essential practices. In Round 3, experts reviewed the final guidance and had the option to rescue items for inclusion in the abridged guidance. Fourteen experts with diverse personal and professional backgrounds participated. Experts added new themes and edited existing ones, creating a comprehensive list of 68 recommendations by consensus and identifying 36 to include in the abridged list of essential practices. They also discussed complex topics such as who these recommendations apply to, the nuances of equitable community engagement, and the dangers of health equity tourism. An expert panel achieved consensus on a comprehensive and abridged list of recommendations for how to conduct research in an antiracist, equitable way. These can inform research teams, regulatory agencies, and funders to improve pediatric research.