Translational Efforts Research Articles

Exploring the Landscape of Hydrogel Therapy for Spinal Cord Injury: A Bibliometric and Visual Analysis (1991–2023)

BackgroundThis study aimed to conduct a bibliometric analysis of the literature on hydrogel therapy for spinal cord injury to visualize the research status, identify hotspots, and explore the development trends in this field. MethodsWeb of science Core Collection database was searched for relevant studies published between January 1991 and December 2023. Data such as journal title, author information, institutional affiliation, country, citation and keywords were extracted. Bibliometrix, CiteSpace and VOSviewer were used to perform bibliometric analysis of the retrieved data. ResultsA total of 1099 articles pertaining to hydrogel therapy for spinal cord injury were retrieved, revealing an upward trajectory in both annual publication volume and cumulative publication volume. Biomaterials emerged as the journal with the highest number of publications and the most rapid cumulative publication growth, contributing 84 articles. Among authors, Shoichet MS stood out with the highest number of publications and citations, totaling 66 articles. The University of Toronto led in institutional contributions with 65 publications, while China dominated in country-specific publications, accounting for 374 articles.However, to foster significant academic achievements, it is imperative for diverse authors, institutions, and countries to enhance collaboration. Current research in this field concentrates on scaffold architecture, nerve growth factor, the fibrotic microenvironment, and guidance channels. Simultaneously, upcoming research directions prioritize 3D bioprinting, injectable hydrogel, inflammation, and nanoparticles within the realm of hydrogel therapy for spinal cord injuries. ConclusionIn summary, this study provided a comprehensive analysis of the current research status and frontiers of hydrogel therapy for spinal cord injury. The findings provide a foundation for future research and clinical translation efforts of hydrogel therapy in this field.

Narrowing lab‐to‐market gaps: Device innovations in fuel generation, solar‐cell, and photodetection

AbstractAcademic translational research efforts to industry are often an underlying sought‐after goal among various researchers. Through the interchanges of research endeavors between academia‐industry, great innovations can/has been achieved that cater to the real‐world application by bridging “industrially relevant” problem solving with pursuing fundamental studies. It is pertinent that most of the studies from university‐level research works may not translate into demonstrable market products due to various reasons. Funding support, individual researcher goals, socioeconomic factors, and most importantly the technical know‐how of generating revenue strategies for startups, are a few of the factors that have slowed the pace of collaborative efforts. However, we believe that the most crucial component is the identification of the critical parameters that solve long‐standing problems that hinder the scale‐up of the lab scale research into marketable products considering the techno‐economic analysis. To illustrate this, we take the three most relevant examples of devices for fuel generation, devices to utilize solar radiation, and devices for detection and other related applications. In this perspective, we provide an in‐depth case study of each of these critical parameters to comment on the direction of research avenues that can serve as step‐stones for the commercialization of university‐level lab research studies.

Interruption of perivascular and perirenal adipose tissue thromboinflammation rescues prediabetic cardioautonomic and renovascular deterioration.

The cardiovascular and renovascular complications of metabolic deterioration are associated with localized adipose tissue dysfunction. We have previously demonstrated that metabolic impairment delineated the heightened vulnerability of both the perivascular (PVAT) and perirenal adipose tissue (PRAT) depots to hypoxia and inflammation, predisposing to cardioautonomic, vascular and renal deterioration. Interventions either addressing underlying metabolic disturbances or halting adipose tissue dysfunction rescued the observed pathological and functional manifestations. Several lines of evidence implicate adipose tissue thromboinflammation, which entails the activation of the proinflammatory properties of the blood clotting cascade, in the pathogenesis of metabolic and cardiovascular diseases. Despite offering valuable tools to interrupt the thromboinflammatory cycle, there exists a significant knowledge gap regarding the potential pleiotropic effects of anticoagulant drugs on adipose inflammation and cardiovascular function. As such, a systemic investigation of the consequences of PVAT and PRAT thromboinflammation and its interruption in the context of metabolic disease has not been attempted. Here, using an established prediabetic rat model, we demonstrate that metabolic disturbances are associated with PVAT and PRAT thromboinflammation in addition to cardioautonomic, vascular and renal functional decline. Administration of rivaroxaban, a FXa inhibitor, reduced PVAT and PRAT thromboinflammation and ameliorated the cardioautonomic, vascular and renal deterioration associated with prediabetes. Our present work outlines the involvement of PVAT and PRAT thromboinflammation during early metabolic derangement and offers novel perspectives into targeting adipose tissue thrombo-inflammatory pathways for the management its complications in future translational efforts.

Systemic lupus erythematosus: one year in review 2024.

Systemic lupus erythematosus (SLE) is classically regarded as the landmark of systemic autoimmune diseases, characterised by protean, multi-systemic manifestations and a highly variable clinical course.Over the last years, both clinical and translational clinical research efforts led to significant steps forward in management and treatment of SLE. However, numerous aspects of SLE, from pathogenesis to treatment, still remain challenging, and several unmet needs persist for both patients and physicians. Following the previous annual reviews of this series, herewith, we aim to report the most relevant new updates on SLE, issued in 2023. In particular, we focused on biomarkers, clinical aspects and outcomes, comorbidities, as well as new treatment targets and real-world evidence.

Vocalic contrasts in Zotung

Though very few Maraic languages from the South Central branch of Tibeto-Burman are represented in the existing body of phonetics literature, they are of interest in that they appear to contain typologically unique dense high vowel systems. Zotung, spoken by approximately 100 000 people in Chin State in western Burma and in diaspora communities, is one such language (Eberhard et al., 2022). The only linguistic scholarship on Zotung (Shintani, 2015) is an extensive wordlist with brief preliminary comments on the syllable shape, tone, and vowel inventories; however, acoustic analyses are absent. To augment Shintani (2015) and further elucidate the vowel inventory of Zotung, we present data from an older male speaker deeply involved with Zotung translation, preservation, and literacy efforts, who hails originally from Tingsi on the far southern border of the Zotung speaking area. Based on analysis of 553 tokens collected via a wordlist, we substantiate some of the findings reported by Shintani (2015) and document several important differences. Shintani reported 8 monophthongal vowel qualities; we find 10: [i, y, e, ø, æ, ə, a, u, o, ɔ]. Shintani also reported an expansive diphthong inventory; our data support this claim, with 9 total vowels that can be categorized as diphthongs.

The importance of translational science within the respiratory field.

The Translational Science Working Group at the European Respiratory Society (ERS) aims to bridge the gap between basic and clinical science by providing a platform where scientists, clinicians and experts in the respiratory field can actively shape translational research. For the 2023 Congress, dedicated translational science sessions were created and sessions of interest to many assemblies from the clinical and the scientific point of view were tagged as translational sessions, attracting clinical and scientific experts to the same room to discuss relevant topics and strengthening translational efforts among all ERS assemblies.

Cholangiocarcinoma: Recent Advances in Molecular Pathobiology and Therapeutic Approaches.

Cholangiocarcinomas (CCA) pose a complex challenge in oncology due to diverse etiologies, necessitating tailored therapeutic approaches. This review discusses the risk factors, molecular pathology, and current therapeutic options for CCA and explores the emerging strategies encompassing targeted therapies, immunotherapy, novel compounds from natural sources, and modulation of gut microbiota. CCA are driven by an intricate landscape of genetic mutations, epigenetic dysregulation, and post-transcriptional modification, which differs based on geography (e.g., for liver fluke versus non-liver fluke-driven CCA) and exposure to environmental carcinogens (e.g., exposure to aristolochic acid). Liquid biopsy, including circulating cell-free DNA, is a potential diagnostic tool for CCA, which warrants further investigations. Currently, surgical resection is the primary curative treatment for CCA despite the technical challenges. Adjuvant chemotherapy, including cisplatin and gemcitabine, is standard for advanced, unresectable, or recurrent CCA. Second-line therapy options, such as FOLFOX (oxaliplatin and 5-FU), and the significance of radiation therapy in adjuvant, neoadjuvant, and palliative settings are also discussed. This review underscores the need for personalized therapies and demonstrates the shift towards precision medicine in CCA treatment. The development of targeted therapies, including FDA-approved drugs inhibiting FGFR2 gene fusions and IDH1 mutations, is of major research focus. Investigations into immune checkpoint inhibitors have also revealed potential clinical benefits, although improvements in survival remain elusive, especially across patient demographics. Novel compounds from natural sources exhibit anti-CCA activity, while microbiota dysbiosis emerges as a potential contributor to CCA progression, necessitating further exploration of their direct impact and mechanisms through in-depth research and clinical studies. In the future, extensive translational research efforts are imperative to bridge existing gaps and optimize therapeutic strategies to improve therapeutic outcomes for this complex malignancy.

Immunological characterization of a long-lasting response in a patient with metastatic triple-negative breast cancer treated with PD-1 and LAG-3 blockade

In patients with advanced triple-negative breast cancer (TNBC), translational research efforts are needed to improve the clinical efficacy of immunotherapy with checkpoint inhibitors. Here, we report on the immunological characterization of an exceptional, long-lasting, tumor complete response in a patient with metastatic TNBC treated with dual PD-1 and LAG-3 blockade within the phase I/II study CLAG525X2101C (NCT02460224) The pre-treatment tumor biopsy revealed the presence of a CD3+ and CD8+ cell infiltrate, with few PD1+ cells, rare CD4+ cells, and an absence of both NK cells and LAG3 expression. Conversely, tumor cells exhibited positive staining for the three primary LAG-3 ligands (HLA-DR, FGL-1, and galectin-3), while being negative for PD-L1. In peripheral blood, baseline expression of LAG-3 and PD-1 was observed in circulating immune cells. Following treatment initiation, there was a rapid increase in proliferating granzyme-B+ NK and T cells, including CD4+ T cells, alongside a reduction in myeloid-derived suppressor cells. The role of LAG-3 expression on circulating NK cells, as well as the expression of LAG-3 ligands on tumor cells and the early modulation of circulating cytotoxic CD4+ T cells warrant further investigation as exploitable predictive biomarkers for dual PD-1 and LAG-3 blockade.Trial registration: NCT02460224. Registered 02/06/2015.

Neutralizing GDF-15 in muscle-invasive bladder cancer (MIBC): A neoadjuvant immunotherapy trial of visugromab (CTL-002) in combination with the anti-PD1 antibody nivolumab (GDFather-Neo).

TPS712 Background: Neoadjuvant chemotherapy (NACT) is a well-established treatment modality in MIBC but suffers from limited activity and significant toxicity. Neoadjuvant immunotherapy (I/O) demonstrated clinical safety and efficacy in various solid tumors including MIBC, with potentially less toxicity. Results from previous studies of single-agent I/O indicated a proportion of pathologic complete responses (ypT0N0) similar to that reported with NACT. Therefore, improving ypT0N0 responses remains a major task for treatment of MIBC. Increasing evidence emerged that Growth and Differentiation Factor 15 (GDF-15) plays a critical local immunosuppressive role. Apart from blocking immune-cell entry into tissues GDF-15 also has major impact on the formation of the immune synapse. Many tumors overexpress GDF-15 and have hijacked this mechanism to block I/O therapy success. Various translational research efforts indicated that GDF-15 may play a significant role for immunosuppression and T-cell exclusion in urothelial carcinoma (UC). Visugromab (CTL-002) is a GDF-15 neutralizing IgG4 monoclonal antibody that demonstrated in Phase 1 a favorable safety profile and promising clinical activity with durable and deep responses in PD-1/PD-L1 relapsed/refractory metastatic solid tumors in combination with the anti-PD1 antibody Nivolumab (Nivo)*. The Neo-GDFather trial is intended to investigate the combination of Visugromab with Nivo vs. Nivo monotherapy as neoadjuvant therapy for MIBC in patients (pts) who are ineligible for or elect not to undergo NACT. Primary endpoints are the complete pathologic response rate and radiologic response. Methods: Multi-center, parallel-cohorts and single-blinded Phase 2 study of neoadjuvant therapy in pts planned for radical cystectomy (RC). A total number of 30 subjects with stage T2-T4N0M0 MIBC will be enrolled and assigned 1:1 to receive either Nivo + Visugromab or Nivo + Placebo after stratification for CPS PD-L1 expression and cT-stage. Other inclusion criteria comprise an ECOG performance status 0-1 and a pure/predominant UC histology. No statistical assumptions were undertaken at this stage.Treatment consists of three 4-week cycles [i.v., Q4Wk], and RC is planned 4-8 weeks after last dose of study drug. After RC, pts will follow standard recommendations of EAU guidelines. Primary endpoints are the proportion of ypT0N0 response and radiologic response rate. Secondary endpoints comprise additional efficacy parameter, surgical and medical safety, PK and PD assessments. Translational research includes evaluation of immunologic parameters in the tumor, other immune-correlates and molecular profiles, as well as evaluation of treatment-emergent cytokine and chemokine profiles in peripheral blood. * Melero et al., #2501 ASCO Annual Meeting 2023 Oral Abstract Session. Clinical trial information: Not yet available.

The Impact of a Centralized Plastic Surgery Research Infrastructure on Scholarly Productivity and Output.

Although research and innovation is a key within the field of plastic and reconstructive surgery, the impact of team structure, interpersonal dynamics, and/or standardized infrastructure on scholarly output has been infrequently studied. In this work, we present the formation and implementation of a novel plastic surgery research program that aims to unite previously disparate clinical and translational research efforts at our institution to facilitate critical inquiry. From July 2022 to June 2023, our department launched a pilot research program based on three pillars: (1) formalization of a research curriculum (monthly research meetings for agenda setting and discussion for project honing, formal research leadership for meeting facilitation and workflow regulation), (2) development of a centralized database to compile ongoing research (Google Drive repository to house all ongoing research documents, facilitate real-time editing, and provide resources/templates for assisting in the research process), and (3) bolstering of a core research identity built on mentorship and collaboration (more frequent interactions to shift previously siloed faculty-student mentorship into a robust milieu of intercollaboration). During the first year, we saw an increased number of publications and presentations, as well as robust participation and contribution from faculty, residents, and medical students. Future directions will focus on addressing resource limitation, such as project idea availability and funding, to sustain the success and growth of this novel research infrastructure.

Parental self-regulation and engagement in emotion socialization: A systematic review.

Parental emotion-related socialization behaviors (ERSBs)-including reactions to emotions, emotional expressiveness, and emotion-related discussion-can foster or hinder children and adolescents' self-regulation development. Toward a goal of identifying specific mechanisms by which children and adolescents develop skillful, adaptive self-regulation or, conversely, self-regulation difficulties and psychopathology, it is crucial to identify processes that shape and maintain parental engagement in ERSBs. This present study is a systematic review of the associations between parental self-regulation and three different ERSBs (reactions to emotions, emotional expressiveness, and emotion-related discussion), building upon research that posits parental top-down self-regulation (i.e., emotion regulation, executive function, and effortful control) is critical for parenting behavior. Fifty-three studies were identified for inclusion. All but four of these studies were cross-sectional, limiting conclusions that could be drawn regarding whether parental self-regulation is associated with ERSBs over time. Studies used a wide range of methods (e.g., self-report, physiological assessment, observer ratings) to assess both parental self-regulation and ERSBs, rendering a meta-analysis premature. Across studies included in the review, parental self-regulation was positively associated with supportive ERSBs and negatively associated with unsupportive ERSBs. Future directions for research and implications for translational efforts are discussed. (PsycInfo Database Record (c) 2024 APA, all rights reserved).

Abstract B022: Targeting epithelial-mesenchymal plasticity and CD73 to enhance responses of breast cancers to immune checkpoint blockade therapies

Abstract Immune checkpoint blockade (ICB) therapy has generated dramatic responses in certain types of human tumors however, the response of breast cancers has been largely limited. Epithelial-mesenchymal plasticity (EMP) enables carcinoma cells to metastasize, gain tumor-initiating ability and mount resistance to chemotherapies. In addition, we have demonstrated that this plasticity program also contributes to the establishment of an immunosuppressive tumor microenvironment and confers resistance to ICB therapy (Dongre and Weinberg 2019). By establishing novel, preclinical models of more-epithelial or more-mesenchymal breast tumors, we observed that epithelial tumors recruit CD8+ T-cells to their microenvironment and are sensitive to anti-CTLA4 ICB. In contrast, mesenchymal tumors recruit Tregs and M2-like macrophages and are resistant to the same treatment (Dongre et al., 2017). Strikingly, abrogation of CD73 from more-mesenchymal cells completely sensitizes otherwise refractory tumors to anti-CTLA4 ICB (Dongre et al., 2021). These findings demonstrated for the first time that more-mesenchymal breast cancer cells can be completely sensitized to anti-tumor immunity by interrupting certain cell-intrinsic signaling channels. However, the underlying mechanisms of such sensitization remain elusive. Additionally, the regulatory networks that control the expression of CD73 itself in more-mesenchymal but not epithelial breast cancer cells are not well defined. To determine the subset of T-cells that is functionally important in sensitizing mesenchymal tumors lacking CD73, we depleted either conventional CD4+ T-cells or CD8+ cytotoxic T-cells in combinatoin with ICB. While responding mice recruited both T-cells to their tumors, only CD4+ T-cells (and not CD8+ T-cells) were functionally important in driving sensitization. Along these lines, more-mesenchymal cancer cells lacking CD73 failed to respond to anti-CTLA4 ICB when propagated in genetically engineered mice lacking CD4+ T-cells relative to wild type controls. Importantly, depletion of CD4+ T-cells also prevented the recruitment of peripheral CD8+ T-cells to responding tumors, thereby driving resistance to ICB. In addition, we observed that human triple negative breast cancer cell lines expressed the highest amount of CD73 relative to hormone receptor-positive cell lines. Most importantly, activating EMP in human breast cancer cells by doxycycline-controlled expression of various transcription factors, induced the expression of CD73. Taken together, our work demonstrates that (i) the phenotypic plasticity of breast cancer cells can predict responses to ICB (ii) targeting CD73 can completely sensitize more-mesenchymal tumors to anti-CTLA4 ICB in a CD4+ T-cell dependent fashion and; (iii) altering the cellular plasticity of cancer cells can regulate CD73 expression. Given the highly refractory nature of more-mesenchymal cancer cells, our findings hold tremendous potential in aiding translational efforts to target cancer plasticity to enhance responses of breast cancers to ICB therapy. Citation Format: Anushka Dongre. Targeting epithelial-mesenchymal plasticity and CD73 to enhance responses of breast cancers to immune checkpoint blockade therapies [abstract]. In: Proceedings of the AACR Special Conference in Cancer Research: Advances in Breast Cancer Research; 2023 Oct 19-22; San Diego, California. Philadelphia (PA): AACR; Cancer Res 2024;84(3 Suppl_1):Abstract nr B022.

Recalibrating the Why and Whom of Animal Models in Parkinson Disease: A Clinician's Perspective.

Animal models have been used to gain pathophysiologic insights into Parkinson's disease (PD) and aid in the translational efforts of interventions with therapeutic potential in human clinical trials. However, no disease-modifying therapy for PD has successfully emerged from model predictions. These translational disappointments warrant a reappraisal of the types of preclinical questions asked of animal models. Besides the limitations of experimental designs, the one-size convergence and oversimplification yielded by a model cannot recapitulate the molecular diversity within and between PD patients. Here, we compare the strengths and pitfalls of different models, review the discrepancies between animal and human data on similar pathologic and molecular mechanisms, assess the potential of organoids as novel modeling tools, and evaluate the types of questions for which models can guide and misguide. We propose that animal models may be of greatest utility in the evaluation of molecular mechanisms, neural pathways, drug toxicity, and safety but can be unreliable or misleading when used to generate pathophysiologic hypotheses or predict therapeutic efficacy for compounds with potential neuroprotective effects in humans. To enhance the translational disease-modification potential, the modeling must reflect the biology not of a diseased population but of subtypes of diseased humans to distinguish What data are relevant and to Whom.

Towards Predicting Post-editing Effort with Source Text Readability

This paper investigates the impact of source text readability on the effort of post-editing English-Chinese Neural Machine Translation (NMT) output. Six readability formulas, including both traditional and newer ones, were employed to measure readability, and their predictive power towards post-editing effort was evaluated. Keystroke logging, self-report questionnaires, and retrospective protocols were applied to collect the data of post-editing for general text type from thirty-four student translators. The results reveal that: 1) readability has a significant yet weak effect on cognitive effort, while its impact on temporal and technical effort is less pronounced; 2) high NMT quality may alleviate the effect of readability; 3) readability formulas have the ability to predict post-editing effort to a certain extent, and newer formulas such as the Crowdsourced Algorithm of Reading Comprehension (CAREC) outperformed traditional formulas in most cases. Apart from readability formulas, the study shows that some fine-grained reading-related linguistic features are good predictors of post-editing time. Finally, this paper provides implications for automatic effort estimation in the translation industry.

Bridging the gap between pregnancy loss research and policy and practice: insights from a qualitative survey with knowledge users

BackgroundThe loss of a pregnancy or the death of baby around the time of their birth can have profound impacts on parents, families and staff involved. There is much opportunity to enhance the systematic uptake of evidence-based interventions to enhance service provision, lived experiences and outcomes. Challenges exist to translating pregnancy loss research evidence into policy and practice, however. Pregnancy loss remains a neglected area of research and resourcing and is steeped in stigma. While barriers and facilitators to the use of research evidence by decision-makers in public health and health services are well documented, we aimed to better understand the factors that influence the translation of pregnancy loss research into practice and policy.MethodsWe conducted a qualitative online survey of pregnancy loss research knowledge users in Ireland, identified through our clinical and academic networks, between January and March 2022. The survey comprised ten questions, with three closed questions, informed by the Knowledge Translation Planning Template©. Questions included who could benefit from pregnancy loss research, perceived barriers and facilitators to the use of research evidence and preferred knowledge translation strategies. We analysed data using reflexive thematic analysis.ResultsWe included data from 46 participants in our analysis, from which we generated two central themes. The first—‘End the silence; stigma and inequality around pregnancy loss to enhance awareness and understanding, public health and services and supports’—addresses issues related to the stigma, sensitivities and silence, lack of awareness and understanding, and lack of relevance or priority afforded to pregnancy loss. The second theme—‘Use a range of tailored, accessible approaches to engage a large, diverse range of knowledge users’—highlights the need to use relevant, accessible, and engaging information, resources or materials in knowledge translation efforts, and a variety of tailored approaches to suit different audiences, including materials, workshops/webinars, media, knowledge brokers and champions or opinion leaders.ConclusionsOur analysis provides rich insights into the barriers and facilitators to knowledge translation in the field of pregnancy loss research. We identified key strategies that can be used to inform knowledge translation planning in Ireland, and which have international applicability.

The Multifaceted Role of Cofilin in Neurodegeneration and Stroke: Insights into Pathogenesis and Targeting as a Therapy.

This comprehensive review explores the complex role of cofilin, an actin-binding protein, across various neurodegenerative diseases (Alzheimer's, Parkinson's, schizophrenia, amyotrophic lateral sclerosis (ALS), Huntington's) and stroke. Cofilin is an essential protein in cytoskeletal dynamics, and any dysregulation could lead to potentially serious complications. Cofilin's involvement is underscored by its impact on pathological hallmarks like Aβ plaques and α-synuclein aggregates, triggering synaptic dysfunction, dendritic spine loss, and impaired neuronal plasticity, leading to cognitive decline. In Parkinson's disease, cofilin collaborates with α-synuclein, exacerbating neurotoxicity and impairing mitochondrial and axonal function. ALS and frontotemporal dementia showcase cofilin's association with genetic factors like C9ORF72, affecting actin dynamics and contributing to neurotoxicity. Huntington's disease brings cofilin into focus by impairing microglial migration and influencing synaptic plasticity through AMPA receptor regulation. Alzheimer's, Parkinson's, and schizophrenia exhibit 14-3-3 proteins in cofilin dysregulation as a shared pathological mechanism. In the case of stroke, cofilin takes center stage, mediating neurotoxicity and neuronal cell death. Notably, there is a potential overlap in the pathologies and involvement of cofilin in various diseases. In this context, referencing cofilin dysfunction could provide valuable insights into the common pathologies associated with the aforementioned conditions. Moreover, this review explores promising therapeutic interventions, including cofilin inhibitors and gene therapy, demonstrating efficacy in preclinical models. Challenges in inhibitor development, brain delivery, tissue/cell specificity, and long-term safety are acknowledged, emphasizing the need for precision drug therapy. The call to action involves collaborative research, biomarker identification, and advancing translational efforts. Cofilin emerges as a pivotal player, offering potential as a therapeutic target. However, unraveling its complexities requires concerted multidisciplinary efforts for nuanced and effective interventions across the intricate landscape of neurodegenerative diseases and stroke, presenting a hopeful avenue for improved patient care.

Research Translation for International Development: A Literature Review and Framework for Evidence Use and Partner Engagement

Many research-to-practice approaches exist, yet fundamental differences in interpretation and uneven application of research translation approaches create a real challenge in generating research-driven solutions for development challenges. In this review, we aim to clarify the plethora of approaches to increase research uptake into international development practice and policy. Through a qualitative analysis of 93 articles, we identified four interrelated factors that differentiate research translation approaches. Building off the variation expressed across these factors, we propose a conceptual framework called the Research Translation Continuum. This framework illustrates the range of ways to produce useful evidence and the range of ways that academics and practitioners can collaborate. Our study makes a unique contribution by providing a conceptual framework for guiding research translation efforts in international development. We conclude that critical reflexive engagement is needed to situate, use, and produce evidence for development policy and practice.

Pharmacology of a Plant Virus Immunotherapy Candidate for Peritoneal Metastatic Ovarian Cancer.

Due to the increasing incidence of cancer, there is a need to develop new platforms that can combat this disease. Cancer immunotherapy is a platform that takes advantage of the immune system to recognize and eradicate tumors and metastases. Our lab has identified a plant virus nanoparticle, cowpea mosaic virus (CPMV) as a promising approach for cancer immunotherapy. When administered intratumorally, CPMV relieves the immune system of tumor-induced immunosuppression and reprograms the tumor microenvironment into an activated state to launch systemic antitumor immunity. The efficacy of CPMV has been tested in many tumor models and in canine cancer patients with promising results: tumor shrinkage, systemic efficacy (abscopal effect), and immune memory to prevent recurrence. To translate this drug candidate from the bench to the clinic, studies that investigate the safety, pharmacology, and toxicity are needed. In this work, we describe the efficacy of CPMV against a metastatic ovarian tumor model and investigate the biodistribution of CPMV after single or repeated intraperitoneal administration in tumor-bearing and healthy mice. CPMV shows good retention in the tumor nodules and broad bioavailability with no apparent organ toxicity based on histopathology. Data indicate persistence of the viral RNA, which remains detectable 2 weeks post final administration, a phenomenon also observed with some mammalian viral infections. Lastly, while protein was not detected in stool or urine, RNA was shed through excretion from mice; however, there was no evidence that RNA was infectious to plants. Taken together, the data indicate that systemic administration results in broad bioavailability with no apparent toxicity. While RNA is shed from the subjects, data suggest agronomical safety. This data is consistent with prior reports and provides support for translational efforts.

Co-Producing the International Pediatric Oncology Exercise Guidelines (iPOEG) Toolkit with End-Users

The international Pediatric Oncology Exercise Guidelines (iPOEG) support physical activity among children and adolescents affected by cancer. Knowledge translation efforts are needed to ensure that those who will use and/or benefit from the iPOEG have access to it. This mixed-methods study followed co-production principles as guided by an integrated knowledge translation approach within the Knowledge to Action (KTA) Framework, to engage end-users (i.e., professionals and patients/caregivers) to: (1) identify the types of resources needed; (2) co-produce an iPOEG brand; (3) co-produce resources and content; and (4) co-produce dissemination plans to distribute the iPOEG Toolkit (i.e., resources and content). End-users indicated requiring resources such as posters, infographics, social media posts, and videos, and co-created resource content covering quick tips to get active and movement-related education and information. Generated strategies to disseminate the iPOEG Toolkit included: (1) academic presentations; (2) brief education sessions and facilitated discussions to different end-user groups; (3) engaging champions from different end-user groups; (4) emails and email reminders; (5) mainstream news outlets (e.g., newspaper, magazines, or segments on the television [i.e., local news]); and (6) social media. Co-production of the iPOEG Toolkit and dissemination plan were guided by two phases within the KTA framework to build tools that can promote the reach of the iPOEG, ultimately increasing physical activity in this population.

Psychedelics for acquired brain injury: a review of molecular mechanisms and therapeutic potential.

Acquired brain injury (ABI), such as traumatic brain injury and stroke, is a leading cause of disability worldwide, resulting in debilitating acute and chronic symptoms, as well as an increased risk of developing neurological and neurodegenerative disorders. These symptoms can stem from various neurophysiological insults, including neuroinflammation, oxidative stress, imbalances in neurotransmission, and impaired neuroplasticity. Despite advancements in medical technology and treatment interventions, managing ABI remains a significant challenge. Emerging evidence suggests that psychedelics may rapidly improve neurobehavioral outcomes in patients with various disorders that share physiological similarities with ABI. However, research specifically focussed on psychedelics for ABI is limited. This narrative literature review explores the neurochemical properties of psychedelics as a therapeutic intervention for ABI, with a focus on serotonin receptors, sigma-1 receptors, and neurotrophic signalling associated with neuroprotection, neuroplasticity, and neuroinflammation. The promotion of neuronal growth, cell survival, and anti-inflammatory properties exhibited by psychedelics strongly supports their potential benefit in managing ABI. Further research and translational efforts are required to elucidate their therapeutic mechanisms of action and to evaluate their effectiveness in treating the acute and chronic phases of ABI.