Translational Efforts Research Articles

Morphological complexity as a predictor of cognitive effort in neural machine translation post-editing

Abstract This study examines how morphological complexity affects cognitive effort in neural machine translation (NMT) post-editing across six languages. Analysis of the DivEMT dataset shows that morphologically richer target languages like Ukrainian and Turkish require more editing time, keystrokes, and frequent pauses, indicating higher cognitive demands. Vietnamese, despite simpler morphology, also showed high cognitive effort, suggesting other factors like syntax influence processing load. Mean Size of Paradigm (MSP) analysis confirmed Ukrainian and Turkish’s high morphological complexity compared to isolating languages like Vietnamese. Higher error rates in morphologically rich languages demonstrate increased editing needs. While user perceptions varied, the data reveals that greater linguistic distance correlates with higher cognitive effort in NMT post-editing, showing typological divergence impacts beyond morphology alone.

Bioinspired micro- and nanostructured systems for cancer therapy.

Numerous organisms in nature have demonstrated enhanced biocompatibility, precise tumor targeting capabilities, and efficient tissue traversal within the human body. Drawing inspiration from these organisms, researchers have employed bioengineering, bioconjugation, and micro- or nanotechnology to fabricate bioinspired micro- and nanostructured systems. These systems play a crucial role in addressing the limitations of conventional anticancer drugs and nanomaterials concerning biocompatibility, effective penetration of physiological barriers, as well as selective tumor targeting, thereby leading to improved therapeutic efficacy while minimizing nonspecific adverse effects on healthy cells. Consequently, extensive exploration of these bioinspired micro- and nanostructured systems has been undertaken across various cancer treatment modalities with some progressing into preclinical or clinical stages. However, our understanding of this field remains limited which may impede research progress, clinical translation efforts, and practical applications. Therefore, this study presents a systematic classification of bioinspired micro- and nanostructured systems for cancer therapy that comprehensively elucidates their sources of inspiration and design principles. Furthermore, it extensively discusses the current status of clinical translation efforts while identifying prevailing challenges and exploring future prospects. This work will establish a robust theoretical framework and serve as a valuable reference to facilitate advancements in research and clinical application within this field.

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.

Surveying, mapping, and translating: how property rights were created in Shanghai, 1860–1900?

Abstract From 1860 to 1900, a modern system of property rights emerged in the International Settlement in Shanghai. This paper examines the largely overlooked process by which the Shanghai Municipal Council (SMC) brought about a system of well-functioning property rights through land surveys, mapping, and assessments. These methods worked hand-in-hand with road planning and construction in facilitating the expansion of the International Settlement to the Chinese-controlled area. Colonial officials, merchants, and Chinese intellectuals worked collectively and sometimes separately to generate knowledge about land and property by translating terms in the Chinese tradition. It argues that the efforts in institution-building and translation helped normalize the definition of property rights as things exclusively owned, strengthening the SMC's control over the land in Shanghai. These processes illuminate the relationship between empire-making and property rights by showing how property rights emerged and functioned in a semi-colonial context where multiple foreign authorities coexisted with the local government. The relatively secure system of property rights, which both foreign and Chinese merchants exploited, formed the foundation of a prosperous Shanghai in the twentieth century.

IMMU-32. DIPEPTIDYL PEPTIDASE-4 (DPP-4) MEDIATED CD8+ T-CELL REGULATION IN GLIOBLASTOMA

Abstract Glioblastoma (GBM) remains to be one of the deadliest cancers with poor prognosis and limited treatment options. While immunotherapies have revolutionized the field for other cancers, GBM remains resistant to these types of interventions partly due to its highly immunosuppressive tumor microenvironment, which is characterized by accumulation of exhausted CD8+ T cells. Therefore, there is a pressing need to identify molecular targets for improve anti-tumorigenic T cell response. Previous studies in our laboratory identified dipeptidyl peptidase-4 (DPP-4), an exopeptidase and a membrane-bound signaling receptor, as a potential marker of immunosuppression in GBM. While DPP-4 is well-drugged due to its role in insulin metabolism, the function of DPP-4 in immune regulation and cancer remains poorly defined. I observed that DPP-4 is highly expressed by CD8+ T cells GBM patients and preclinical models. Furthermore, DPP-4 levels increased with the exhaustion or memory differentiation of effector T cell. Pharmaceutical inhibition of DPP-4 enriched expression of genes related to lymphocyte activation and mitochondrial metabolism. These transcriptional changes were accompanied by enhanced T cell proliferation, cytotoxic function, and effector mediator production under exhaustion conditions. These findings suggest that pharmacological inhibition of DPP-4 promotes anti-tumorigenic function of CD8+ T-cell by preventing exhaustion and support future translational efforts to repurpose DPP-4 inhibitors as immunotherapy agents in GBM, given their favorable safety profiles.

Advances in the mathematical modeling of posttreatment control of HIV-1.

Several new intervention strategies have shown significant improvements over antiretroviral therapy (ART) in eliciting lasting posttreatment control (PTC) of HIV-1. Advances in mathematical modelling have offered mechanistic insights into PTC and the workings of these interventions. We review these advances. Broadly neutralizing antibody (bNAb)-based therapies have shown large increases over ART in the frequency and the duration of PTC elicited. Early viral dynamics models of PTC with ART have been advanced to elucidate the underlying mechanisms, including the role of CD8+ T cells. These models characterize PTC as an alternative set-point, with low viral load, and predict routes to achieving it. Large-scale omic datasets have offered new insights into viral and host factors associated with PTC. Correspondingly, new classes of models, including those using learning techniques, have helped exploit these datasets and deduce causal links underlying the associations. Models have also offered insights into therapies that either target the proviral reservoir, modulate immune responses, or both, assessing their translatability. Advances in mathematical modeling have helped better characterize PTC, elucidated and quantified mechanisms with which interventions elicit it, and informed translational efforts.

Engineered Cardiac Tissues as a Platform for CRISPR-Based Mitogen Discovery.

Improved understanding of cardiomyocyte (CM) cell cycle regulation may allow researchers to stimulate pro-regenerative effects in injured hearts or promote maturation of human stem cell-derived CMs. Gene therapies, in particular, hold promise to induce controlled proliferation of endogenous or transplanted CMs via transient activation of mitogenic processes. Methods to identify and characterize candidate cardiac mitogens in vitro can accelerate translational efforts and contribute to the understanding of the complex regulatory landscape of CM proliferation and postnatal maturation. In this study, A CRISPR knockout-based screening strategy using in vitro neonatal rat ventricular myocyte (NRVM) monolayers is established, followed by candidate mitogen validation in mature 3-D engineered cardiac tissues (ECTs). This screen identified knockout of the purine metabolism enzyme adenosine deaminase (ADA-KO) as an effective pro-mitogenic stimulus. RNA-sequencing of ECTs further reveals increased pentose phosphate pathway (PPP) activity as the primary driver of ADA-KO-induced CM cycling. Inhibition of the pathway's rate limiting enzyme, glucose-6-phosphate dehydrogenase (G6PD), prevented ADA-KO induced CM cycling, while increasing PPPactivityviaG6PD overexpression increased CM cycling. Together, this study demonstrates the development and application of a genetic/tissue engineering platform forin vitrodiscovery and validation of new candidate mitogens affecting regenerative or maturation states of cardiomyocytes.

The Diverse Aspects of Uterine Serous Cancer: An NCI workshop on the status of and opportunities for advancement of research.

The marked increase in incidence and mortality in endometrial cancer over the last two decades is driven in part by rising rates of higher grade, more aggressive endometrial cancers with mutations in TP53, uterine serous cancers and their dedifferentiated component, uterine carcinosarcomas (collectively USC). USC rates have been increasing among all racial and ethnic groups, with higher rates of this aggressive uterine cancer in Black women. The National Cancer Institute (NCI) hosted a workshop in June 2023 to examine the diverse aspects of USC across epidemiology, biology, and molecular genetics, and to advance knowledge from basic to preclinical and translational efforts. Key stakeholders came together including basic scientists, clinical investigators, and patient advocates to identify critical research gaps that, when addressed, would facilitate more comprehensive and rapid progress in understanding and ultimately treating USC across all patients. NCI released a supplemental funding opportunity (NOT-CA-24-044) in Spring 2024 to facilitate rapid translation of these recommendations.

Oxyntomodulin physiology and its therapeutic development in obesity and associated complications.

Incretins, such as glucagon-like peptide-1 (GLP1) and glucose-dependent insulinotropic polypeptide (GIP), have advanced the treatment landscape of obesity to a new pinnacle. As opposed to singular incretin effects, oxyntomodulin (OXM) activates glucagon receptors (GCGR) and glucagon-like peptide-1 receptors (GLP1R), demonstrating a more dynamic range of effects that are more likely to align with evolving 'health gains' goals in obesity care. Here, we will review the molecular insights from their inception to recent developments and challenges. This review will discuss the physiological actions of OXM, primarily appetite regulation, energy expenditure, and glucose homeostasis. Finally, we will shed light on the development of OXM-based therapies for obesity and associated complications, and outline important considerations for more translational efforts.

Current State of Stereotactic Body Radiation Therapy for Genitourinary Malignancies.

Stereotactic body radiation therapy (SBRT) involves the delivery of high-dose, highly precise radiation therapy to focal sites of gross tumor involvement. Recent advances in radiation planning and image guidance have facilitated rapid growth in the evidence for and use of SBRT, particularly for genitourinary malignancies, where the underlying radiobiology often suggests greater tumor sensitivity to SBRT than to conventionally fractionated radiation. Here, we review the evolution of SBRT for patients with prostate adenocarcinoma and renal cell carcinoma. We discuss state-of-the-art trials, indications, and future directions in the SBRT-based management of both localized and metastatic disease. With rapidly growing enthusiasm and evidence, clinical and translational research efforts on the biology and outcomes of SBRT over the coming decade will be crucial to refining the indications, technical approach, and synergistic combinations of SBRT with highly active systemic therapies and improve the efficacy and quality-of-life outcomes for patients with genitourinary malignancies.

A decade later: Assessing pregnant women's perspectives on non-invasive prenatal testing (NIPT) in Saudi Arabia

Since its introduction a decade ago, non-invasive prenatal testing (NIPT) has been recognized as a highly accurate and safe screening option for expecting mothers, with its efficacy hinging on awareness, perceptions, and understanding of the test. We surveyed pregnant women in Saudi Arabia between December 2023 and February 2024 to assess the knowledge and acceptability of NIPT among them. A total of 212 pregnant women from various risk levels, socioeconomic statuses, and trimesters participated in the study, which was carried out at King Saud University Medical City (KSUMC) via online forms. This study investigated factors affecting attitudes towards NIPT, including financial burden. Data were analyzed with descriptive statistics and chi-square tests to assess correlations. The survey revealed a significant lack of awareness about NIPT, with 64.6 % of participants unfamiliar with the test and 93.3 % answering knowledge-related questions incorrectly. Although 74.1 % were willing to undergo NIPT if it were free, only 30 % were willing to pay 1500 SAR (400 USD). These findings underscore the need for targeted knowledge translation efforts to enhance awareness and understanding of NIPT among pregnant women, highlighting the importance of addressing financial barriers and increasing educational outreach. Further research and interventions are needed to promote the uptake of NIPT and enhance the quality of antenatal care programs in Saudi Arabia.

Various Problems And Solutions In Translating Between Arabic And Indonesian

This research examines the challenges and strategies involved in translating Arabic texts, particularly Quranic verses, into Indonesian. Given the significant linguistic and cultural differences between Arabic and Indonesian, translation efforts face numerous obstacles, including issues related to morphology, syntax, semantics, and cultural context. These challenges are compounded by the complexity of translating polysemous words, synonyms, idioms, and metaphors. This research employs qualitative methods, focusing on the translation processes, and offers solutions grounded in established translation techniques. By analyzing selected Quranic verses and creatively crafted Indonesian examples, the research highlights the importance of maintaining grammatical integrity, adapting idioms appropriately, and addressing untranslatability and collocations to ensure that translations are accurate and culturally relevant.

Balancing realist review outputs with the needs of policymakers and practitioners.

A realist review is a theory-driven approach to synthesizing evidence based on the realist philosophy of science. Realist reviews are conducted to provide the policy and practice community with a rich, detailed, and practical understanding of complex social interventions that will likely be of much more use to them when planning and implementing programs. Robust realist reviews must balance philosophical engagement, methodological rigor, and relevance to practice. Nevertheless, they have been criticized for being more philosophically inclined and less methodologically robust, with findings that have little implication for practice. Using the philosophy/Epistemology→methodology→theory→practice concept flow, we report how we balanced philosophical principles and practical insights in a recently conducted realist review on participatory practices that impact the benefits of non-communicable disease research and interventions in low- and middle-income countries. If realist review reviews are not comprehensible enough for these practitioners, their utility and relevance may suffer from being limited to a specialist cohort of academics. We propose that realist review findings and outputs must be framed and communicated to meaningfully engage practitioners without undertaking translational efforts.

Challenges of Translating Idiomatic Expressions: A Cross-Linguistic Analysis at a University in Hanoi, Vietnam

This study investigates the challenges students face when translating idiomatic expressions between English and Vietnamese and explores how linguistic and cultural factors influence the translation process. Utilizing a combination of translation task analysis and focus group discussions, the research reveals that students frequently rely on literal translations, resulting in inaccurate or nonsensical outcomes due to their inability to grasp the figurative meanings of idioms. Cultural mismatches, particularly the absence of equivalent expressions in Vietnamese, further complicate translation efforts, leading to significant misunderstandings. Additionally, linguistic barriers, such as syntactic differences between English and Vietnamese, hinder students' ability to produce natural and accurate translations of idiomatic expressions. The findings emphasize the critical role of cultural knowledge and syntactic flexibility in effective idiomatic translation. To address these challenges, the study recommends that translation training programs place greater emphasis on idiomatic understanding and cross-cultural competence. This study contributes to the growing body of literature on idiomatic translation by highlighting the interplay of linguistic and cultural factors and suggesting strategies to enhance translation accuracy.

Conducting Assessments of Community-Based Programs for Individuals with Dementia and their Family Caregivers.

While the gold standard for intervention science is the randomized controlled trial (RCT), there is growing emphasis on the practical implementation and evaluation of evidence-based programs into community agencies. Assessment of program efficacy by community-based organizations can confirm planned delivery of services, implementation fidelity, and demonstrate positive outcomes, which can provide justification for funding. Methods and measures used in an RCT, however, often cannot be implemented in non-research settings and different approaches are needed. This manuscript reviews the emerging literature on program evaluation work and draws upon the authors' experiences conducting evaluations with three community-based organizations funded by Administration for Community Living to implement programs for individuals with dementia and their family care partners. This manuscript argues for an examination of the expectations of evaluation efforts for translation of research-based trials to practice and emphasizes three main strategies for assessment: (1) Development of brief tailored assessments; (2) Measuring fidelity of implementation of the program; and (3) Measuring acceptability of the program to clients.

Free sugars in the Canadian diet: a research summary and future directions for food policy.

Until recently, most dietary guidelines and related food policies in Canada focused on total sugars, but recent evidence suggests that free sugars are of greater public health concern. Starting in 2017, our research group received federal funding to fill critical gaps related to free sugars and health. In this commentary, we describe our work related to tracking free sugars in the Canadian food supply and simulating the diet and health impacts of product reformulation. We then summarize how our work has influenced policymaking in Canada with examples of our knowledge translation efforts, and provide a future research and policy agenda based on our findings. Overall, there is significant room for Canadian food policies to target free sugars reductions in food and diets to address overconsumption of this nutrient of public health concern.

Chromatin accessibility is associated with therapeutic response in prostate cancer.

Treatment of advanced prostate cancer is challenging due to a lack of effective therapies. Therefore, it is important to understand the molecular mechanisms underlying therapeutic resistance in prostate cancer and to identify promising drug targets offering significant clinical advantages. Given the pivotal role of dysregulated transcriptional programs in the therapeutic response, it is essential to prioritize translational efforts targeting cancer-associated transcription factors (TFs). The present study investigated whether chromatin accessibility was associated with therapeutic resistance in prostate cancer using Assay for Transposase-Accessible Chromatin with sequencing (ATAC-seq) data. The bioinformatics analysis identified differences in chromatin accessibility between the drug response (Remission) and drug resistance (Disease) groups. Additionally, a significant association was observed between chromatin accessibility, transcriptional output and TF activity. Among TFs, forkhead box protein M1 (FOXM1) was identified as a TF with high activity and expression in the Disease group. Notably, the results of the computational analysis were validated by FOXM1 knockdown experiments, which resulted in suppressed cell proliferation and enhanced therapeutic sensitivity in prostate cancer cells. The present findings demonstrated that chromatin accessibility and TF activity may be associated with therapeutic resistance in prostate cancer. Additionally, these results provide the basis for future investigations aimed at understanding the molecular mechanisms of drug resistance and developing novel therapeutic approaches for prostate cancer.

Analgesia and peripheral c-fiber modulation by selective Nav1.8 inhibition in rhesus.

Voltage-gated sodium (Nav) channels present untapped therapeutic value for better and safer pain medications. The Nav1.8 channel isoform is of particular interest because of its location on peripheral pain fibers and demonstrated role in rodent preclinical pain and neurophysiological assays. To-date, no inhibitors of this channel have been approved as drugs for treating painful conditions in human, possibly because of challenges in developing a sufficiently selective drug-like molecule with necessary potency not only in human but also across preclinical species critical to the preclinical development path of drug discovery. In addition, the relevance of rodent pain assays to the human condition is under increasing scrutiny as a number of mechanisms (or at the very least molecules) that are active in rodents have not translated to humans, and direct impact on pain fibers has not been confirmed in vivo. In this report, we have leveraged numerous physiological end points in nonhuman primates to evaluate the analgesic and pharmacodynamic activity of a novel, potent, and selective Nav1.8 inhibitor compound, MSD199. These pharmacodynamic biomarkers provide important confirmation of the in vivo impact of Nav1.8 inhibition on peripheral pain fibers in primates and have high translational potential to the clinical setting. These findings may thus greatly improve success of translational drug discovery efforts toward better and safer pain medications, as well as the understanding of primate biology of Nav1.8 inhibition broadly.

Translating Traditional Folk Poetry: The Perception of Translators and Translation Students and the Reality in Saudi Society

Despite the massive presence and influence of traditional folk poetry (TFP) within Saudi society, the efforts to translate such works remain very limited. While many authors and researchers have examined the impact of this literary genre and illustrated its prominence, academic investigations into the difficulties of translating TFP works are almost nonexistent. This is also true about studies that focus on the overarching sentiment regarding these efforts among those who are associated with the field of language and translation and among members of the general public. This paper thus aims at examining these perspectives and outlining the challenges translation trainees face when performing tasks in this field. The data for this study was collected through the dissemination of a questionnaire and the analysis of a translation task assigned to university students in an academic program for English language and translation. The qualitative and quantitative analysis of the data shows that the level of acceptance of TFP translation efforts is strongly connected to the degree of association with the field of languages and translation, with individuals from outside these circles being less supportive of initiatives in this domain. Additionally, the paper identified several obstacles and challenges encountered by translation students working on TFP texts. The paper concludes with a number of recommendations and suggestions that can, hopefully, contribute to the efforts to raise awareness about translating TFP and to the process of improving the current state of translation within this field.

A critical systematic review of extracellular vesicle clinical trials.

This systematic review examines the landscape of extracellular vesicle (EV)-related clinical trials to elucidate the field's trends in clinical applications and EV-related methodologies, with an additional focus on the acknowledgement of EV subpopulations. By analysing data from public reporting repositories, we catalogued 471 EV-related clinical trials to date, with indications for over 200 diseases. Diagnostics and companion diagnostics represented the bulk of EV-related clinical trials with cancer being the most frequent application. EV-related therapeutics trials mainly utilized mesenchymal stromal cell (MSC) EVs and were most frequently used for treatment of respiratory illnesses. Ultracentrifugation and RNA-sequencing were the most common isolation and characterization techniques; however, methodology for each was not frequently reported in study records. Most of the reported characterization relied on bulk characterization of EV isolates, with only 11% utilizing EV subpopulations in their experimental design. While this may be connected to a lack of available techniques suitable for clinical implementation, it also highlights the opportunity for use of EV subpopulations to improve translational efforts. As academic research identifies more chemically distinct subpopulations and technologies for their enrichment, we forecast to more refined EV trials in the near future. This review emphasizes the need for meticulous methodological reporting and consideration of EV subpopulations to enhance the translational success of EV-based interventions, pointing towards a paradigm shift in personalized medicine.