Translational Approach Research Articles

An assessment of translating religious and magical aspects in "Arabian nights" into English

This thesis discusses the difficulties of translating "Arabian Nights" from Arabic to English, focusing on cultural and religious elements. It analyzes translation strategies from the 19th century to the present by using Katharina Reiss' text typology framework. English translations nevertheless influenced by historical biases and misconceptions. Modern translations show more cultural sensitivity but struggle to fully convey nuances. Market expectations often lead to domestication in translation approaches. The research emphasizes the tension between making the text accessible to Western audiences while keeping its cultural authenticity. It contributes to discussions on literary translation and cultural preservation, emphasizing the need for more complex, culturally aware approaches in translating works across diverse linguistic and cultural landscapes. This study provides insights to inform future translation efforts and cross-cultural literary studies, addressing the difficult balance between reader accessibility and cultural integrity in literary translation.

Definitional Challenges in Understanding Hypertrophic Cardiomyopathy

Hypertrophic cardiomyopathy (HCM) is the most common hereditary cardiomyopathy. It is often caused by mutations of genes encoding for sarcomeric or sarcomere-associated proteins. Despite its clinical importance, divergent definitions are published by major cardiology societies. Some regard HCM as a specific genetic disease, whereas others define it as a broad ‘spectrum of the thick heart’. The present narrative review aimed to assess both definitions from a pathoanatomical perspective. As a conjoint interdisciplinary and translational approach is needed to further increase knowledge and improve the understanding of HCM, the PubMed database was searched using several advanced search algorithms to explore the perspectives of the (forensic) pathologist, clinician, and basic researcher regarding the difference between the definitions of HCM. This discrepancy between definitions can impact critical data, such as prevalence and mortality rate, and complicate the understanding of the disease. For example, due to the different definitions, research findings regarding molecular changes from studies applying the narrow definition cannot be simply extended to the ‘spectrum’ of HCM.

Brain Injury and Neurodegeneration: Molecular, Functional, and Translational Approach 2.0

The brain is composed of different cells, such as neurons, glia, endothelial cells, etc [...]

CSIG-17. ADHESION GPCR BAI1/ADGRB1 CAN BLOCK IGF1R-MEDIATED GROWTH SIGNALLING, INCREASE RADIOSENSITIVITY AND AUGMENT SURVIVAL IN MEDULLOBLASTOMA

Abstract Medulloblastoma (MB) is an aggressive pediatric brain tumors and increased knowledge about the disease mechanisms is needed to develop new therapeutic approaches. Brain-specific Angiogenesis Inhibitor 1 (BAI1/ADGRB1) is an adhesion GPCR receptor and tumor suppressor epigenetically silenced in MB. Our prior studies showed that BAI1 can bind the MDM2 E3 ubiquitin ligase and relocate it to the cell membrane, thereby preventing it from degrading p53 in the nucleus (Zhu et al, Cancer Cell, 2018). Whether other MDM2 targets are affected by this relocation that may be functionally important in MB development is unknown. We hypothesized that BAI1-mediated relocation of MDM2 might destabilize cell surface oncogenic receptors and found that BAI1 stimulates IGF1R poly-ubiquitination and degradation. Mechanistically, BAI1 fosters MDM2-IGF1R interaction through beta-arrestins, adaptor proteins connecting MDM2 to IGF1R. Epigenetic reactivation of BAI1 expression suppressed Stat3 and Akt signaling, and radio-sensitized MB cells, leading to significantly improved survival in orthotopic MB xenograft models in mice regardless of tumor p53 mutation status. These findings are important as they demonstrate that BAI1 has dual anti-tumor effects in MB through MDM2 membrane re-localization, stabilizing p53 and blocking IGF1R signaling. They further suggest that epigenetic targeting of BAI1 is a promising therapeutic approach for clinical translation.

Bioactive Self‐Assembled Nanoregulator Enhances Hematoma Resolution and Inhibits Neuroinflammation in the Treatment of Intracerebral Hemorrhage

AbstractHematoma and secondary neuroinflammation continue to pose a significant challenge in the clinical treatment of intracerebral hemorrhage (ICH). This study describes a nanoregulator formed through the self‐assembly of Mg2+ and signal regulatory protein α (SIRPα) DNAzyme (SDz), aimed at enhancing hematoma resolution and inhibiting neuroinflammation in the treatment of ICH. The structure of SDz collapses in response to the acidic endo/lysosomal microenvironment of microglia, releasing Mg2+ and the SIRPα DNAzyme. The Mg2+ then acts as a cofactor to activate the SIRPα DNAzyme. By blocking the CD47‐SIRPα signaling pathway, microglia can rapidly and effectively phagocytose red blood cells (RBCs), thereby promoting the clearance of the hematoma. Simultaneously, Mg2+ reset the microglia to the M2 phenotype by inhibiting the MYD88/MAPK/NF‐κB signaling pathway, thereby modulating the inflammatory microenvironment of ICH. This co‐delivery and synergistic strategy resulted in a significant reduction in hematoma size, decreasing from 11.90 to 5.84 mm3, and promoted recovery from ICH with minimal systemic side effects. This simple yet highly effective nanoplatform, which involves complex synergistic mechanisms, proves to be effective for ICH therapy and holds great promise for introducing novel perspectives into clinical and translational approaches for ICH.

Linguistic Obstacles Faced in Translating Some Unique Qur’anic Cultural Lexical Items into English: Reexploring Some Translation Approaches

Linguistic Obstacles Faced in Translating Some Unique Qur’anic Cultural Lexical Items into English: Reexploring Some Translation Approaches

A Contrastive Study of Chinese-English Translation of Ancient Poetry from the Perspective of Aesthetics of Reception: A Case Study of the Two Translations of Vain Longing

The Chinese literary classic "Dream of the Red Chamber" features a variety of poems and songs, with "Vain Longing," which serves as its theme song, being particularly popular among readers both domestically and internationally. Among the many translations available, those by Yang Xianyi and Gladys Yang, along with Hawkes' version, are the most prominent and hold significant research value. Acceptance Aesthetics, which emerged from the German critical school in the 20th century, provides a fresh lens through which to view the translation of ancient Chinese poetry. This paper utilizes Aesthetics of reception as its theoretical framework and focuses on the English translations of "Vain Longing" by Yang Xianyi and Gladys Yang as well as Hawkes found in "Dream of the Red Chamber." By examining their translation philosophies and approaches, this study aims to contribute insights for translating ancient poetry within literary contexts while enhancing global appreciation for Chinese poetic beauty and promoting classical Chinese culture.

The European Health Data Space as a Case Study

ABSTRACTIn May 2022, the European Commission proposed the launch of a health‐specific data sharing framework called the European Health Data Space (EHDS), underpinned by legislation, for the use of electronic health data by patients and for research, innovation, policy‐making, patient safety, statistics, or regulatory purposes. In this essay, I review some of its more contentious features based on the latest version of the legislative proposal. I suggest that the EHDS is a useful case study to illustrate the need for a translational bioethics approach that shines a critical analytical light on contentious aspects of large‐scale research infrastructures.

Pharmacological activation of STAT1-GSDME pyroptotic circuitry reinforces epigenetic immunotherapy for hepatocellular carcinoma.

Genomic screening uncovered interferon-gamma (IFNγ) pathway defects in tumours refractory to immune checkpoint blockade (ICB). However, its non-mutational regulation and reversibility for therapeutic development remain less understood. We aimed to identify ICB resistance-associated druggable histone deacetylases (HDACs) and develop a readily translatable combination approach for patients with hepatocellular carcinoma (HCC). We correlated the prognostic outcomes of HCC patients from a pembrolizumab trial (NCT03419481) with tumourous cell expressions of all HDAC isoforms by single-cell RNA sequencing. We investigated the therapeutic efficacy and mechanism of action of selective HDAC inhibition in 4 ICB-resistant orthotopic and spontaneous models using immune profiling, single-cell multiomics and chromatin immunoprecipitation-sequencing and verified by genetic modulations and co-culture systems. HCC patients showing higher HDAC1/2/3 expressions exhibited deficient IFNγ signalling and poorer survival on ICB therapy. Transient treatment of a selective class-I HDAC inhibitor CXD101 resensitised HDAC1/2/3high tumours to ICB therapies, resulting in CD8+T cell-dependent antitumour and memory T cell responses. Mechanistically, CXD101 synergised with ICB to stimulate STAT1-driven antitumour immunity through enhanced chromatin accessibility and H3K27 hyperacetylation of IFNγ-responsive genes. Intratumoural recruitment of IFNγ+GZMB+cytotoxic lymphocytes further promoted cleavage of CXD101-induced Gasdermin E (GSDME) to trigger pyroptosis in a STAT1-dependent manner. Notably, deletion of GSDME mimicked STAT1 knockout in abolishing the antitumour efficacy and survival benefit of CXD101-ICB combination therapy by thwarting both pyroptotic and IFNγ responses. Our immunoepigenetic strategy harnesses IFNγ-mediated network to augment the cancer-immunity cycle, revealing a self-reinforcing STAT1-GSDME pyroptotic circuitry as the mechanistic basis for an ongoing phase-II trial to tackle ICB resistance (NCT05873244).

A translational approach for understanding hyperalgesia: What has the high-frequency electrical stimulation model taught us?

High-frequency electrical stimulation (HFS) of C fiber nociceptors induces long-term potentiation (LTP) at the first spinal synapse. This spinal LTP is believed to play a role in the amplification of pain. However, the effects of HFS are probably not restricted to the spinal cord. A recent study showed that HFS increases cortical responses to noxious stimuli in a porcine model. Are these increased cortical responses a correlate of spinal LTP and do we observe the same in humans?

Norms of Translating Medical Terms in English Patient Information Leaflets into Kurdish

Patient Information Leaflets (PILs) are documents included in medicine packages and provide important information about the medication for patients. This study investigates the translation problems of English PILs into Sorani Kurdish. The aim of this study is to identify the translation procedures used for translating medical terminologies in PILs for lay people. It also aims to reveal which translational norms are operating in Kurdish translations of PILs. To do so, the study employs a corpus of 150 English PILs along with their Kurdish translations. To analyse the corpus, the researcher adopts Toury’s (1995-2012) three-phase methodology within the descriptive approach of translation. It also uses Vinay and Darbelnet’s (1995) translation procedures to determine how translators handled terminological rendering in the Kurdish PILs. According to the findings, nine types of translation procedures were used in translating the terminologies, with borrowing had the highest frequency, and modulation having the lowest frequency. They also revealed that Toury’s initial norms were predominantly operating in the translated PILs which labelled them as adequate translations. The translators’ choice to closely follow the original PILs was indicative of their attempt to meet the expectations of PILs’s target users, thus, revealing Chesterman’s expectancy norms therein. The study concludes that the translation of PILs into Kurdish is not regulated within the medical field and that is mainly related to the absence of an officially regulated body in the Kurdistan Region of Iraq. It also concludes that while the seemingly established norm of PIL translation into Kurdish highly relies on English borrowings, it is a significant step towards developing Kurdish medical language.

A holistic approach to supporting death in the home: Implementation of a home hospice program in a northern community–A study protocol

Introduction To enhance support for individuals at end of life to die at home, a new community-driven home-based hospice program was developed–Home Hospice. This wholistic hospice care program, co-designed by hospice care staff, community end-of-life care providers, researchers, and health systems decision-makers, will provide around the clock care to clients and their families. Methods and analysis This mixed methods study, guided by a process evaluation framework, will use secondary client and caregiver data collected as part of regular Home Hospice program processes, as well as primary interview data collected from caregivers at least three months post-death of the client and from hospice staff and volunteers involved in the Home Hospice program. Analysis will include descriptive statistical analysis of quantitative data and thematic analysis employing an inductive and a deductive qualitative analysis approach. Ethics Ethics approval has been received from the University of Northern British Columbia (File No: 6009117). All individuals and caregivers who enroll in the Home Hospice program will be invited to participate in this study. At three months post-death of the client, hospice staff will contact caregivers to ask if they would like to participate in a one-on-one interview with a research team member. Staff and volunteers will also be eligible to participate in one-on-one interviews with research team members. De-identified participant data will be provided by hospice staff to the research team. All participants will provide informed consent prior to participation in the study. Dissemination This study will use an integrated Knowledge Translation/Knowledge Mobilization (iKTKM) lens wherein the research team will work closely and meaningfully with knowledge users and community partners at all stages. Evidence-based and targeted iKTKM products will be created, including community event presentations and social media posts to share findings with participant and community audiences. Further, findings will be disseminated at conferences, workshops, and policy rounds with academic and decision-making audiences. Preliminary and full project findings will be published in high-quality open access journals. Strengths and limitations of this study Co-design of Home Hospice program and evaluation metrics involves researchers, hospice staff, health systems decision-makers, and community members. Evaluation metrics involve prospective collection of service utilization from client, family, hospice, and health systems perspectives. Integrated knowledge translation approach which frames the knowledge dissemination plan for the study findings focuses on a range of audiences, including local citizens, hospice and community end-of-life care providers, health systems decision-makers, and academic professionals. As a one-year pilot study, the number of clients who may be able to participate in this program will be approximately 50 persons.

Reduced intestinal-to-diffuse conversion and immunosuppressive responses underlie superiority of neoadjuvant immunochemotherapy in gastric adenocarcinoma.

Neoadjuvant immunochemotherapy (NAIC) achieves superior clinical benefits over neoadjuvant chemotherapy (NAC) in multiple types of human cancers, including gastric adenocarcinoma (GAC). However, it is poorly understood how the malignant epithelial cells and tumor immune microenvironment (TIME) might respond distinctly to NAIC and NAC that underlies therapeutic efficacy. Here treatment-naive and paired tumor tissues from multiple centers were subjected to pathological, immunological, and transcriptomic analysis. NAIC demonstrated significantly increased rate of pathological complete response compared to NAC (pCR: 25%vs. 4%, p<0.05). Interestingly, pretreatment intestinal subtype of Lauren's classification was predictive of pathologic regression following NAIC, but not NAC. A substantial portion of cancers underwent intestinal-to-diffuse transition, which occurred less following NAIC and correlated with treatment failure. Moreover, NAIC prevented reprogramming to an immunosuppressive TIME with less active fibroblasts and exhausted CD8+ T cells, and increased numbers of mature tertiary lymphoid structures. Mechanistically, activation of the tumor necrosis factor alpha (TNFα)/nuclear factor-kappa B (NF-κB) signaling pathway was associated with response to NAIC. Together, NAIC is superior to NAC for locally advanced GAC, likely due to reduced intestinal-to-diffuse conversion and reprogramming to an immuno-active TIME. Modulation of the histological conversion and immunosuppressive TIME could be translatable approaches to improve neoadjuvant therapeutic efficacy.

NCOR1 orchestrates macrophage inflammation in heart failure with preserved ejection fraction: a translational study

Abstract Background/Introduction Inflammatory response is a key player in heart failure with preserved ejection fraction (HFpEF) but the underlying mechanisms are poorly understood. Recent studies have shown a critical involvement of cardiac macrophage activation in myocardial remodeling thus contributing to HFpEF. Purpose To investigate the role of cardiac macrophage inflammation in experimental and human HFpEF. Methods We employed a translational approach combining human and murine LV myocardial tissue, FACS analysis of cardiac immune cells, in vitro experiments in RAW 264.7 cells exposed to metabolic stress by palmitic acid (PA), bone marrow-derived macrophages from healthy and HFpEF mice, cardiomyocytes (H9c2), endothelial cells (HAECs) as well as ex vivo functional analyses in LV tissues. Human LV myocardial samples were used to evaluate the pro-inflammatory activity of macrophages in the HFpEF myocardium. Induction of HFpEF in mice was done through a validated mouse model combining metabolic (high-fat diet) and hemodynamic stress (L-NAME). Cardiac function was investigated by high resolution ultrasound imaging (Vevo3100) and the LV myocardial samples were used to study the macrophage polarization and their inflammatory activity. Based on interrogation of available RNA-seq datasets – showing the transcriptional repressor NCOR1 as a relevant signature in macrophages during cardiac inflammation, we generated myeloid cell-specific NCOR1 knockout (Ncor1-KO) transgenic mice to investigate the in vivo effects of NCOR1 deletion on the HFpEF phenotype. Results The expression of macrophage markers in human LV specimens showed an increase in pro-inflammatory macrophages (M1) and a decrease in regulatory macrophages (M2) as compared to age-matched control mice. HFpEF mice showed increased expression of vascular adhesion molecules (ICAM1, ICAM2, E-selectin) and a significant recruitment of M1 macrophages as proved by qPCR, WB, and flow cytometry analysis. Of interest, diastolic dysfunction - assessed by E/A ratio and isovolumic relaxation time (IVRT) – and lung congestion were significantly reduced in mice with macrophage NCOR1 deletion as compared to WT littermates, while exercise tolerance was significantly improved. These findings were associated with a reduction of myocardial inflammation (TNF-a, IL6, IL-1b) in Ncor1-KO mice. In vitro assays showed that stimulation of macrophages with PA induced M1 type switch and increased NCOR1, TNF-a, IL-6, and IL-1b levels, whereas NCOR1 depletion prevented detrimental changes of macrophage secretome (Fig.2). Conclusion NCOR1 is a crucial regulator of immune response and macrophage inflammation in the heart. Our findings highlight its potential as a target for therapies aimed at preventing myocardial damage in HFpEF.

Promoting vaccination for newly arrived migrants: a multistakeholder collaboration pilot

Abstract Access to vaccinations for Newly Arrived Migrants (NAMs) is a critical public health issue. In the context of the project ‘Increased Access for Newly Arrived Migrants-AcToVax4NAM’ (Grant No. 101018349, 3rd EU Health Program), DPHID-SAP and GLOB-ISS conducted a pilot aimed at developing and testing a system pathway to promote and vaccinate NAMs. The pilot began with the creation of a team between researchers from DPHID-SAP and GLOB-ISS, professionals from two services of the Local Health Authority and from a first reception centre (CAS) in Rome area. An integrated knowledge translation approach was used, which facilitated the collaborative development of strategies and actions of the pilot. The team then reached out to other ‘professionals FOR health’ involved in the vaccination process of NAMs, i.e. physicians from Temporarily Present Foreigners (STP) outpatient clinics, General Practitioners and Pediatricians. Between July 2023 and April 2024, four actions were developed. 1) analysis of the current access of NAMs to vaccination services and the subsequent development of a contextualized pathway to facilitate vaccinations for NAMs, including catch-up strategies; 2) identification of informed consent and other materials needed to be included in the pathway; subsequently, translated in 10 languages; 3) implementation of vaccine literacy session for CAS staff and NAMs; 4) improvement of immunization information flows to enable assessment of vaccination coverage of NAMs. To evaluate the pilot, the vaccination rate observed during the pilot (January-April 2024) was compared to that occurring in 2023, showing a 36.5-fold increase in the vaccination rate (4 x 100 person-year in 2023 and 155 x 100 p/y in 2024; RR = 36.5 (95%CI 14.6-117.6). The pilot highlighted that a research collaborative approach among various actors facilitated the access to vaccination for NAMs and was an opportunity to turn knowledge into action. Key messages • It is essential to ensure equitable vaccination coverage to reduce under-immunized groups. • Access to vaccination is a key element of the right to health and for collective health protection and it should be a shared responsibility.

Students' perceptions of knowledge reinforcement on indirect prosthetic dental material choices by a translational approach.

The aim of this study is to evaluate students' perceptions of the reinforcement of knowledge via innovative, case-based, hands-on learning regarding indirect prosthetic material choice. Six different clinical cases that represented common prosthetics were used in this simulation training. In each case, clinical pictures were associated with three-dimensional (3D)-printed replicates of final restorations and PolyJet polychromatic models with the goal of enabling students to deliberate and exchange ideas in small groups. After a debriefing session regarding the therapeutic potentialities of the first three cases alongside teachers, a lecture concerning prosthetic material choices was provided, and a zirconia crown was stained by each student to enable them to obtain a better understanding of the dental technician profession. Finally, the latter three cases were studied and analyzed in the same manner. The students' perceived reinforcement of knowledge was recorded before and 1 month after the hands-on simulation training experience, and their satisfaction was evaluated immediately thereafter on Likert scales. Students' perceived reinforcement of knowledge was subjected to statistical evaluation. A high level of overall satisfaction was observed (4.60). All of the items pertaining to students' satisfaction received scores >3. One month after this hands-on approach, students' confidence in their ability to choose a material on the basis of its mechanical, optical, and luting properties increased significantly (from 2.58 to 3.64; from 2.83 to 3.64; and from 2.72 to 3.58, respectively) (p<0.05). This innovative, hands-on approach had a significant positive effect on students' perceived reinforcement of knowledge.

The need for translational bioethics within perinatal healthcare and policy making: A COVID-19 case study

The COVID-19 pandemic highlighted many issues that can occur due to lack of translation between the spheres of bioethics and clinical practice. In this paper, we examine how mothers and newborn infants were inappropriately separated during the initial stages of the pandemic due to inconsistent application of ethical principles in determining policy. One of the significant challenges that translational bioethics face is the complexity regarding its implementation into the health service environment. As outlined in the literature, it may be postulated that responsibility for translating bioethics from philosophical concepts into practice is the duty of those training in philosophical theory and reasoning. However, the use of bioethics in informing clinical practice is not just the case of needing a translator but rather requires an interpreter in the widest sense: professionals attuned to both bioethics and clinical practice, who can communicate with both groups effectively. A two-way dialogue needs to be more cohesively established to ensure clinical practice is guided by ethical principles and to focus academic debate towards the pragmatic issues that require ethical exploration. Utilising the translational bioethics model described by Bærøe and applying it to our perinatal COVID case study, we examine how an integrated translational bioethics approach could have prevented the harm and disruption to mother–infant dyads during the initial phase of the pandemic in 2020.

Diversity of attachment systems in heelwalkers (Mantophasmatodea) – highly specialized, but uniform

BackgroundHeelwalkers possess a highly modified tarsal attachment system. All extant species lift the distalmost tarsomere permanently off the substrate and primarily use their euplantulae for locomotion. The combination of a smooth adhesive pad (arolium) on the pretarsus and fibrillary attachment pads on the euplantulae offers valuable insights for translational approaches, but its infra-order diversity remains unexplored.ResultsWe explored the morphology of the tarsal attachment apparatus of Mantophasmatodea based on a representative taxon sampling spanning a large fraction of species of this group and compared morphological differences in the specialized morphology of this system across species and sexes. Our scanning electron microscope investigation of the tarsi of 11 species (52% of all described extant species) revealed an overall very consistent ground pattern and almost no specific adaptations. There are only minor, but mostly clade-specific differences in the shape of the adhesive setae on the tarsal euplantulae and in the morphology and density of the acanthae on the pretarsal arolium. Both features differ primarily between Austrophasmatidae in comparison to the remaining Mantophasmatodea taxa.ConclusionWe conclude that the strong specialization of the mantophasmatodean tarsal attachment sufficiently copes with the diversity of substrates the insects are exposed to.

Fibroblast stromal support model for predicting human papillomavirus-associated cancer drug responses.

Human papillomavirus-related cancers (HPV+ cancers) remain a significant public health concern, and specific clinical approaches are desperately needed. In translating drug response data from in vitro to in vivo, the fibroblasts of the adjacent stromal support network play a key role. Our study presents the utilization of a fibroblast 2D co-culture system to better predict translational drug assessments for HPV+ cancers. We also suggest that this co-culture system should be considered for other translational approaches. Predicting even a portion of treatment paradigms that may fail in vivo with a co-culture model will yield significant time, effort, resource, and cost efficiencies.

German radiation oncology's next generation: a web-based survey of young biologists, medical physicists, and physicians-from problems to solutions.

Radiation science is of utmost significance not only due to its growing importance for clinical use, but also in everyday life such as in radiation protection questions. The expected increase in cancer incidence due to an aging population combined with technical advancements further implicates this importance and results in ahigher need for sufficient highly educated and motivated personnel. Thus, factors preventing young scientists and medical personnel from entering or remaining in the field need to be identified. Aweb-based questionnaire with one general and three occupation-specific questionnaires for physicians, biologists, and medical physicists working in radiation oncology and research was developed and circulated for 6weeks. While the overall satisfaction of the 218 participants was quite high, there are some points that still need to be addressed in order to ensure acontinuing supply of qualified personnel. Among these were economic pressure, work-life balance, work contracts, protected research time, and ademand for an improved curriculum. Mentoring programs, improved education, and strengthening the value of societies in radiation sciences as well as translational approaches and more flexible working arrangements might ensure ahigh-quality workforce and thus patient care in the future.