Journals
2026 EN
Weberpals Janick · Schneeweiss Sebastian · Kehl Kenneth L.
+17 more
Real‐world evidence (RWE) is increasingly used to complement findings from randomized controlled trials (RCTs), contextualizing the effectiveness and safety of medical interventions as delivered in routine clinical practice. Advances in the curation and accessibility of electronic health record (EHR) data present the opportunity to utilize real‐world data (RWD) to investigate therapeutic areas including oncology, where administrative healthcare claims databases alone are often not fit‐for‐purpose. The RCT DUPLICATE initiative has previously evaluated when RWE can most appropriately draw causal conclusions by emulating trials for nononcology indications. Here, we present the design and trial selection for the emulation of comparative oncology trials with real‐world evidence (ENCORE) project, which extends this work to oncology. ENCORE is designed to emulate 12 RCTs in four oncology‐specialized EHR databases across four different cancer indications, specifically non‐small‐cell lung cancer, breast cancer, colorectal cancer, and multiple myeloma. It will place special emphasis on systematic evaluation of fitness of data in relation to the study design and statistical analysis for a particular research question and preregistration of study protocols prior to initiation and analysis. Prespecified criteria will assess agreement of treatment effect estimates between RCTs and their respective emulations. Through extensive sensitivity analyses benchmarked against RCT results, the ENCORE project aims to inform understanding of how measurement, design, and analytic decisions influence the interpretation of results from emulated oncology trials using RWD.
Journals
2026 EN
Pignatti Francesco · ElGalaly Tarec Christoffer · Kaiser Martin
+17 more
External comparator cohort (ECC) studies with real‐world data (RWD) may provide more reliable estimates of treatment differences compared to single‐arm trials (SAT), yet they face limitations such as selection bias and data heterogeneity. This study assessed the perceived strength of evidence of ECC studies compared to SAT and randomized controlled studies (RCT). The study included healthcare professionals (HCP) from the European Hematology Association (EHA), the European Society for Medical Oncology (ESMO), and assessors from international regulatory agencies (RA). A conjoint analysis evaluated strength of evidence ratings for establishing an effect on OS for different hypothetical scenarios, based on different designs, RWD quality, and observed OS improvement, for a new cancer treatment for advanced disease and no effective treatments. Participants from HCP organizations rated RWD studies favorably (advantages outweigh disadvantages) more frequently (47.6%; n = 103) compared to RA participants (12.9%; n = 116). Compared to a SAT, a high‐quality RWD ECC study showing a 1.5‐month and 3‐month OS improvement had 2.7 (95% CI: 1.9–3.8) and 14.7 (95% CI: 10.0–21.5) times higher odds of receiving a higher strength of evidence rating, respectively. The OR for RCT v. SAT was 36.4 (95% CI: 24.0–55.2) and 358.4 (95% CI: 217.3–591.3), respectively. Strength of evidence ratings were associated with maximum acceptable risk of severe or symptomatic toxicity. In conclusion, when evaluating the OS of new therapies, ECC studies with RWD, especially when based on high‐quality RWD or demonstrating a larger OS benefit, were rated as more convincing than SAT without a formal control.
Journals
2026 EN
Kang Youngnam · Shariati Kaavian · Cascavita Catherine T.
+4 more
Abstract Bone regeneration depends on coordinated interactions among cells, extracellular matrices, and the dynamic microenvironment within engineered constructs. Mineralized collagen‐glycosaminoglycan (MC‐GAG) scaffolds are designed to replicate key features of native bone matrix, yet their mineral accumulation and mechanical performance remain lower than those of mature bone, making precise evaluation of mineral deposition essential. High‐resolution microCT imaging provides nondestructive, three‐dimensional (3D) visualization of mineral distribution, density, and microarchitecture with substantially improved fidelity. Through dynamic, angle‐dependent calibration and scan‐specific recalibration, our microCT scanner HiCT minimizes motion‐ and temperature‐related artifacts and enables consistent, high‐resolution imaging suitable for small scaffold systems. This protocol outlines an integrated workflow combining high‐resolution microCT scanning with advanced image segmentation to assess mineralization within MC‐GAG scaffolds. The method includes scaffold fabrication, chemical cross‐linking, and human mesenchymal stem cell culture, followed by stable positioning in custom 3D‐printed racks to ensure precise imaging geometry. Reconstruction and threshold‐based segmentation in a DICOM viewer such as ORS Dragonfly allow separation of scaffold structure from higher‐density mineral phases, providing detailed visualization and quantitative analysis of mineral deposition. This reproducible framework enhances the characterization of bone‐regenerative biomaterials and supports efforts to engineer scaffolds that more closely mimic the structural and functional properties of native bone. © 2026 The Author(s). Current Protocols published by Wiley Periodicals LLC. Basic Protocol 1 : Fabrication of bone regenerative mineralized collagen scaffolds Basic Protocol 2 : High‐resolution microCT scanning and microstructural analysis of the MC‐GAG scaffolds
Journals
2026 EN
Kang Youngnam · Shariati Kaavian · Cascavita Catherine T.
+5 more
Abstract Cranial bone regeneration requires coordinated interactions among host cells, extracellular matrices, and the local biomechanical environment to restore both mineralized tissue and structural protection of the brain. Mineralized collagen–glycosaminoglycan (MC–GAG) scaffolds recapitulate key features of native bone matrix and have demonstrated osteogenic potential in preclinical calvarial defect models; yet, robust, quantitative methods are needed to evaluate defect bridging, mineral density, and microarchitectural maturation in vivo. In vivo microcomputed tomography (microCT) enables nondestructive, three‐dimensional (3D) assessment of craniofacial healing with spatial detail sufficient to characterize mineral distribution and structural connectivity across large defects. Here, we describe an integrated workflow that combines scaffold implantation in a rabbit critical‐sized calvarial defect model with standardized in vivo microCT imaging and 3D computational rendering. The framework includes scaffold fabrication and preparation, surgical creation of a critical‐sized calvarial defect with scaffold placement, and in vivo microCT imaging at a single endpoint (6 months post‐surgery). Image datasets are visualized and analyzed using reproducible segmentation software (i.e., ORS Dragonfly) to examine defect repair and extract quantitative intensity‐ and volume‐based metrics, including mineralized tissue volume, mineral density, and microarchitectural parameters. This standardized approach supports objective, image‐based comparison of scaffold designs and treatment strategies, facilitating rigorous evaluation of cranial bone regeneration and accelerating the development of bone‐regenerative biomaterials. © 2026 The Author(s). Current Protocols published by Wiley Periodicals LLC. Basic Protocol 1 : Fabrication of mineralized collagen–based scaffolds Basic Protocol 2 : Surgical creation of rabbit calvarial defects with scaffold implantation and in vivo microCT scanning Basic Protocol 3 : In vivo microCT data visualization, rendering, and analysis of MC–GAG scaffolds‐implanted rabbit calvarial bone defect
Journals
2026 EN
Liu Ran · Ji Chunli · Prentice Catherine
+1 more
ABSTRACT Despite the extensive literature on corporate social responsibility (CSR), the relevance to minority‐owned business enterprises (MBEs) has received limited attention. This research examines how CSR practiced by MBEs affects employee response. Two studies were undertaken to address this relationship. Study 1 employed a mixed‐methods approach to modify the traditional CSR scale for MBEs, referred to as CSR‐MBE in the current study. This scale encompasses two dimensions: General CSR (GCSR) and minority‐specific CSR (MSCSR). Study 2 utilized the CSR‐MBE scale to examine their respective effects on employees through a serial mediation model. The findings demonstrate that MSCSR exerts a stronger influence on employee outcomes, including loyalty, mediated by work meaningfulness, mindfulness, and organizational pride, underscoring the pivotal role of cultural alignment. This study introduces a novel framework for understanding CSR in culturally specific contexts and provides actionable insights for MBEs to leverage culturally resonant CSR strategies, enhancing employee loyalty and achieving a sustainable competitive advantage.
Journals
2026 EN
LehnerMear Rachel · Dixon Kerryn · Xu Yuwei
+2 more
Abstract In England, gender is currently a controversial issue, with debates in social and political spheres increasingly impacting educational policy. Simultaneously, scholarship on gender in Early Childhood Education (ECE) advocates more gender‐sensitive pedagogies to disrupt restrictive and essentialised views. We use Connell's principles of curricular justice to analyse gender's position in England's birth‐to‐five policies. Taking as the lynchpin of our analysis Connell's third principle, the historical production of equality, we trace gender's representation in 14 birth‐to‐five statutory and non‐statutory curriculum documents from 1996 to 2021, identifying the extent to which these curricula support practitioners to teach in just and equitable ways. A picture of curricular injustice becomes evident. Our review highlights how changes in the broader political system result in three shifts in gender's curricular positioning (defined as gender foundations; gender awareness; gender decline) that ultimately fail the needs of the least advantaged and inhibit children's preparation for democratic participation in society. The ideological (re)production of gender (in)justice in the curricula occurs, firstly, through limited references to gender, fluctuations in gender's use over time and gender's siloing in non‐statutory statements. Secondly, conceptual confusion, the use of binary constructs and a reliance on both legal non‐discrimination and an equal opportunity framing restrict gender justice. This review exposes the ways in which the reproduction of social power in the ECE curriculum reinforces gender inequalities, thus raising questions about the curriculum's suitability for supporting socially just, gender‐sensitive pedagogy in ECE. We conclude that now is the time for a renewal of curricular justice.
Journals
2026 EN
Mahjabin Fnu · Hajarat Tara J. · De Leo Alexandra
+2 more
ABSTRACT CIC ‐rearranged sarcomas (CDS) are rare, aggressive undifferentiated small round cell tumors recently classified as a distinct entity by the World Health Organization. These tumors are defined by CIC gene fusions, most commonly CIC::DUX4 , and are associated with poor prognoses and diagnostic challenges, particularly in limited cytological samples. We report the case of a 37‐year‐old male who presented with respiratory symptoms and was found to have mediastinal lymphadenopathy. Fine‐needle aspiration (FNA) of a right paratracheal lymph node revealed hypercellular smears of dyscohesive tumor cells with high nuclear‐to‐cytoplasmic ratios, prominent nucleoli, and cytoplasmic vacuoles. Immunohistochemistry showed positivity for WT1, CD99, and vimentin, while RNA sequencing confirmed a CIC::DUX4 fusion, establishing the diagnosis of CDS. This case highlights the critical role of integrating cytopathology, immunohistochemistry, and molecular diagnostics in identifying CDS, particularly in atypical anatomical sites. Early and accurate diagnosis is essential for guiding clinical management in this rare and aggressive sarcoma subtype.
Journals
2026 EN
Sullivan Abigail J. · Garcia Sophia Eisenberg · Kinsey Maria
+8 more
ABSTRACT This study was part of a longitudinal follow‐up of a 3‐armed randomized controlled trial designed to test the effects of two brief parenting interventions, Play Nicely (PN) and Triple P‐Level 2 (TP2), to a usual care control on parenting outcomes. Female caregivers with an identified index child ( M age = 3.7 years, standard deviation [SD] = 1.7) were recruited through women, infants, and children (WIC) clinics in the greater New Orleans region. At a long‐term ( M years = 5 years, SD = 0.9) follow‐up assessment, respiratory sinus arrhythmia (RSA) was assessed for a subset of these mother–child dyads during three dyadic interaction tasks: a baseline video, an affiliative discussion task, and an active cooperation task. Children displayed a significant decrease in RSA from the baseline video to the affiliative discussion task, whereas mothers displayed a significant decrease in RSA from the discussion task to the active cooperation task. Although no main intervention effects were found, differing patterns of child RSA in intervention groups were observed when accounting for time since intervention. Compared to the control group, children in the TP2 group exhibited relatively stable patterns of RSA, whereas children in the PN group exhibited RSA levels that decreased as time since intervention increased. These divergent patterns may reflect fundamental differences in the developmental scope of the two interventions. Together, these findings suggest that brief parenting interventions may differentially influence the stability of children's autonomic regulation during interactions with their caregiver, depending on their developmental focus and timing of delivery.
Journals
2026 EN
RogersonWood Lara · Sawatari Atomu · Goldsbury Claire S.
+1 more
ABSTRACT The capacity for enhanced experience, modeled as environmental enrichment (EE) in laboratory animals, to drive positive changes in brain circuitry presents a promising avenue in the development of therapies for neurodevelopmental conditions. Less understood are the underlying mechanisms, or potential interactions of EE with other therapeutic approaches. We have previously shown that early exposure to EE can drive the partial repair of miswired uncrossed retinal projections, and the concomitant rescue of a visual behavior, in the Ten‐m3 knockout (KO) mouse. This was associated with a highly spatiotemporally localized upregulation of microglial reactivity in the region where the correction was occurring which peaked around postnatal day (P)25. Aiming to confirm a causal role for microglial‐mediated engulfment in this process, we assessed the effect of daily injections of minocycline or vehicle saline from P18 to P24 (inclusive) on measures of microglial reactivity and anatomical corrective pruning in P25 Ten‐m3 KO mice. While an effect of EE was confirmed at this timepoint, intriguingly, we found that both the vehicle‐ and minocycline‐treated mice had a similar lack of microglial reactivity and showed a marked absence of corrective pruning of their miswired retinal projections. This suggests that the injection procedure itself disrupted the experience‐induced microglial‐mediated circuit repair. These results underscore the highly sensitive nature of EE‐driven corrective pruning actions of microglia and the critical importance of considering and controlling for all aspects of experience.
Journals
2026 EN
Morsanyi Kinga · Paracchini Silvia · Krishnan Saloni
+4 more
ABSTRACT Inconsistencies in the definition and diagnosis of dyslexia continue to impede research, assessment, and intervention. This paper, authored by members of the UK Specific Learning Difficulties Network, critically examines a recent effort to establish a consensus definition and guidance for assessment and intervention for dyslexia, which involved 58 experts from academia, practice and lived experience. The resulting framework offers a developmental, multifactorial and continuum‐based perspective. It expands on prevailing definitions by highlighting the influence of multiple genetic, environmental and cognitive factors, as well as developmental changes in dyslexia profiles. However, unresolved issues remain, including ambiguity around prevalence and the role of general cognitive functioning, and a lack of clear guidance for educators. The definition also lacks clarity on assessment and intervention, especially in global contexts where teaching practice may be highly variable. Co‐occurrence with language and mathematics difficulties is acknowledged but underexplored, limiting implications for practice. Whilst the Delphi method provides useful consensus, we also reflect on its limitations, including potential bias in the composition of the panel. Overall, the framework is a valuable step forward, but unresolved issues remain both from a research perspective and in terms of practical implementation.