Translational Impact Research Articles

Optimizing elderly care: a data-driven AI model for predicting polypharmacy risk using SHARE data

Abstract Background Polypharmacy (PP), which rises with age, is a growing public health challenge, affecting health outcomes and escalating healthcare expenditure. Leveraging the comprehensive European coverage and longitudinality of the Survey of Health, Ageing, and Retirement in Europe (SHARE) study, we aim to assess PP prevalence patterns and identify the most effective machine learning (ML) model for predicting long-term PP risk, as a foundation for a scalable predictive tool. Methods We used data from participants aged above 50 who were present in wave 6 and at least one of the subsequent three waves of the SHARE study, aiming to predict PP risk at 2, 4, and 6-year intervals. PP was defined as the concurrent use of five or more medications. We analyzed PP prevalence trends and selected the predictor variables from wave 6 using LASSO regression analysis. We evaluated eight ML models, namely, ANN, SVM, DT, RF, GB, XGBoost, LightGBM, and CatBoost, using a rigorous cross-validation strategy to ensure robustness and reliability. Results Our analysis reveals an upward trend in PP prevalence across the surveyed countries, with aggregate figures rising from 34.03% (95% CI 33.1-34.9) in wave 7 to 36.75% (95% CI 35.6-37.9) in wave 8, reaching 39.91 (95% CI 38.9-40.9) in wave 9. Additionally, using the Categorical Boosting ML model to predict PP resulted in overall accuracies of 75.08%, 73.7%, and 71.65% and recall rates of 72.83%, 70.48%, and 67.96% for the 2, 4, and 6-year intervals, respectively. Conclusions This study reveals a rising trend of PP across European countries and demonstrates the potential of using longitudinal data and ML to enhance PP prediction. The tool developed represents a step forward in risk stratification, which would be particularly beneficial in practical settings where family physicians or pharmacists could employ the tool to monitor elderly patients, predict and thus prevent PP, and reduce the negative health and economic impact associated with it. Key messages • The integration of machine learning with longitudinal data presents a significant advance in polypharmacy risk prediction. • The tool we developed highlights the potential translational impact of our findings.

Preconception and prenatal vitamin D associations with positive behavioral health in Black children.

Low levels of vitamin D during pregnancy are associated with offspring behavioral problems but little is known about pre-pregnancy influences. Additionally, Black American individuals are underrepresented in studies, limiting translational impact. We tested independent and interactive effects of preconception and prenatal vitamin D in Black women in relation to positive behavioral and emotional outcomes in early childhood. Black-identifying participants (N = 156) enrolled in the longitudinal Pittsburgh Girls Study (PGS) provided venous blood samples before and during pregnancy to measure 25-hydroxyvitamin D (25[OH]D) levels. Participants completed questionnaires assessing sociodemographic factors, depression severity and life stress, and later reported on child behavioral and emotional problems and prosocial behavior between 2 and 4 years. Mean serum 25(OH)D concentrations were 15.5 ng/ml (s.d. = 7.7) before pregnancy and 18.0 ng/ml (s.d. = 9.2) during pregnancy; below the sufficiency threshold according to commonly used dietary guidelines. After adjusting for covariates, prenatal 25(OH)D was negatively related to behavior problems and positively related to prosocial behavior in children, although the association attenuated for behavior problems after accounting for preconception 25(OH)D, which may reflect patterns of stability. Maternal 25(OH)D was unrelated to child emotional problems, and no synergistic effects of 25(OH)D timing were observed for any child outcome. Findings have relevance for Black women living in the northeast U.S. Results suggest specific associations between maternal vitamin D and positive behaviors in early childhood, regardless of sufficiency levels and suggest potential opportunities for early interventions to support healthy child development.

Translation and localization of food menus on mobile delivery apps in the United Arab Emirates: a multimodal and reception study

ABSTRACT This study investigates the quality of menu translation and localization on food delivery apps and its impact on the user experience. A corpus of food menus was collected from the Talabat app and analyzed from a multimodal perspective adopting Li’s (2019) framework and using NVivo qualitative data analysis software. A coding framework was created in NVivo to systematically identify translation and localization strategies, and issues related to images of food items. Additionally, an online survey targeting app users was utilized to gather data on preferences and the impact of menu translation and localization on user experience, satisfaction, and purchasing decisions. The analysis revealed that the meaning of food menus involves several layers, including semiotic and textual means, which necessitate approaching their translation from a multimodal perspective. Dish names were mostly transliterated into English and accompanied by an acceptable and clear description of dish information in English. The survey results also revealed that translation quality has a great role in shaping user experience, satisfaction, trust, and expenditure. The findings of this study will be of value to translators, translation trainers, restaurant owners, and food delivery app developers.

Transient Inhibition of Translation Improves Cardiac Function After Ischemia/Reperfusion by Attenuating the Inflammatory Response.

The myocardium adapts to ischemia/reperfusion (I/R) by changes in gene expression, determining the cardiac response to reperfusion. mRNA translation is a key component of gene expression. It is largely unknown how regulation of mRNA translation contributes to cardiac gene expression and inflammation in response to reperfusion and whether it can be targeted to mitigate I/R injury. To examine translation and its impact on gene expression in response to I/R, we measured protein synthesis after reperfusion in vitro and in vivo. Underlying mechanisms of translational control were examined by pharmacological and genetic targeting of translation initiation in mice. Cell type-specific ribosome profiling was performed in mice that had been subjected to I/R to determine the impact of mRNA translation on the regulation of gene expression in cardiomyocytes. Translational regulation of inflammation was studied by quantification of immune cell infiltration, inflammatory gene expression, and cardiac function after short-term inhibition of translation initiation. Reperfusion induced a rapid recovery of translational activity that exceeds baseline levels in the infarct and border zone and is mediated by translation initiation through the mTORC1 (mechanistic target of rapamycin complex 1)-4EBP1 (eIF4E-binding protein 1)-eIF (eukaryotic initiation factor) 4F axis. Cardiomyocyte-specific ribosome profiling identified that I/R increased translation of mRNA networks associated with cardiac inflammation and cell infiltration. Short-term inhibition of the mTORC1-4EBP1-eIF4F axis decreased the expression of proinflammatory cytokines such as Ccl2 (C-C motif chemokine ligand 2) of border zone cardiomyocytes, thereby attenuating Ly6Chi monocyte infiltration and myocardial inflammation. In addition, we identified a systemic immunosuppressive effect of eIF4F translation inhibitors on circulating monocytes, directly inhibiting monocyte infiltration. Short-term pharmacological inhibition of eIF4F complex formation by 4EGI-1 or rapamycin attenuated translation, reduced infarct size, and improved cardiac function after myocardial infarction. Global protein synthesis is inhibited during ischemia and shortly after reperfusion, followed by a recovery of protein synthesis that exceeds baseline levels in the border and infarct zones. Activation of mRNA translation after reperfusion is driven by mTORC1/eIF4F-mediated regulation of initiation and mediates an mRNA network that controls inflammation and monocyte infiltration to the myocardium. Transient inhibition of the mTORC1-/eIF4F axis inhibits translation and attenuates Ly6Chi monocyte infiltration by inhibiting a proinflammatory response at the site of injury and of circulating monocytes.

Integrating priorities at the intersection of cancer and neuroscience.

Cancer neuroscience is a rapidly growing multidisciplinary field that conceptualizes tumors as tissues fully integrated into the nervous system. Recognizing the complexity and challenges in this field is of fundamental importance to achieving the goal of translational impact for cancer patients. Our commentary highlights key scientific priorities, optimal training settings, and roadblocks to translating scientific findings to the clinic in this emerging field, aiming to formulate a transformative and cohesive path forward.

Prediction of homologous recombination deficiency identifies colorectal tumors sensitive to PARP inhibition

The synthetic lethal effect observed with the use of PARP inhibitors (PARPi) with tumors characterized by the loss of key players in the homologous recombination (HR) pathway, commonly referred to as “BRCAness”, is maintaining high interest in oncology. While BRCAness is a well-established feature in breast, ovarian, prostate, and pancreatic carcinomas, our recent findings indicate that up to 15% of colorectal cancers (CRC) also harbor defects in the HR pathway, presenting promising opportunities for innovative therapeutic strategies in CRC patients. We developed a new tool called HRDirect, which builds upon the HRDetect algorithm and is able to predict HR deficiency (HRD) from reference-free tumor samples. We validated HRDirect using matched breast cancer and CRC patient samples. Subsequently, we assessed its efficacy in predicting response to the PARP inhibitor olaparib by comparing it with two other commercial assays: AmoyDx HRD by Amoy Diagnostics and the TruSight Oncology 500 HRD (TSO500-HRD) panel by Illumina NGS technology. While all three approaches successfully identified the most PARPi-sensitive CRC models, HRDirect demonstrated superior precision in distinguishing resistant models compared to AmoyDX and TSO500-HRD, which exhibited overlapping scores between sensitive and resistant cells. Furthermore, we propose integrating HRDirect scoring with ATM and RAD51C immunohistochemical analysis as part of our “composite biomarker approach” to enhance the identification of HRD tumors, with an immediate translational and clinical impact for CRC personalized treatment.

Functional Analysis of Thematic Approach to the Division of Surahs in Two English Contemporary Translations of the Qur’an

Thematic division of Qur’anic chapters (henceforth, surahs) into paragraphs is a recent trend in translating the Qur’an. This thematic approach refers to the translation of Qur’anic surah based on their underlying themes rather than verse-by-verse translation in a bilingual text. Disregarding source text division, some translators divide each Qur’anic surah into paragraphs with subheadings while translating the surahs into English. This paper aimed to reveal how the division and chosen themes for each paragraph of the surahs often differ among translators who choose this thematic approach to the Qur’an translation. The data is collected from two modern thematic English translations of the Qur’an, namely, The Clear Quran by Khattab (2015) and The Majestic Quran by Hussain (2018). Adopting a descriptive design and qualitative research method, the paper aimed at applying Nord’s model of functionalist text analysis to compare the units of analysis selected from three Qur’anic surahs: Q. 86, Q. 87 and Q. 93. These surahs are particularly chosen because they are divided differently in the two translations. The paper queries the impact of thematic translation and text segmentation on the Qur’an translation process, especially in relation to producing loyalty and functional adequacy in the two translations. Nord’s functional model was used to explore the effect of thematic translation in conveying the functions for the intended readership without betraying their trust in that they are reading God’s word in their own language. The findings emphasise that thematic translation tends to violate rather than maintain the original intended functions (skopos) and loyalty to the source text.

Translation into Arabic A study of the negatives and positives

The research aims to shed light on the importance of translation in the Arab Renaissance and its development of the Arabic language in the modern era. Translation is considered one of the most important factors of the modern Arab Renaissance, which began at the beginning of the nineteenth century. The translation movement expanded in Egypt and the Levant in the late nineteenth century, to the point of Some historians believe that it was more active than the translation movement in those countries today. Translation contributed to the development of the Arabic language, as it enabled it to introduce modern terminology and the emergence of new literary genres in Arabic literature, etc.. Through the descriptive and analytical approach followed in the study, I concluded that the impact of translation on the Arabic language has two aspects: one positive and the other negative: the positive impact is represented by enriching Arabic with thousands of vocabulary in science, technology and arts through Arabization, and with very large numbers of vocabulary and expressions through translation, but translation began to negatively affect the nature of the Arabic language in terms of structure, derivation, and incision of new words. The importance of the research is due to mentioning the virtue of translation in enriching the Arabic language in various fields, studying the positives and negatives related to translation into the Arabic language, and clarifying the obstacles that stand before the translator during the translation process and how to deal with them. 2

Exploring the Use of Subtitling in Teaching and Learning English as a Foreign Language: Theories and Applications

Technology occupies a significant resource that can be exploited empirically to contribute to translation learning and research, as it can give enormous opportunities for language learners and educators to exploit in their teaching and provide students with practical learning activities. Many researchers highly recommend the extensive use of IT in enhancing the competence of translation students and L2 learners' language skills. Since there has been an abundance of empirical research studies carried out over the last two decades, many novice researchers cannot review and handle them within their limited time. For this reason, this paper introduces the key researchers who carried out studies on the employment of audiovisual translation (AVT) in language learning and teaching; it explores and reviews the main previous research studies conducted on the impact of audiovisual translation, namely subtitling and subtitles on enhancing language learning. It first considers briefly how audiovisual translation emerged as an independent branch of Translation Studies (ST), then discusses its development as well as its continuity within Translation Studies. It also explores its classifications and highlights future research avenues.

Are we speaking the same language? Exploring the impact of translation on discourse analysis in health professions education.

Are we speaking the same language? Exploring the impact of translation on discourse analysis in health professions education.

Discovery of GuaB inhibitors with efficacy against Acinetobacter baumannii infection.

The emergence of multidrug-resistant bacteria worldwide has renewed interest in discovering antibiotics with novel mechanism of action. For the first time ever, we demonstrate that pharmacological inhibition of de novo guanine biosynthesis is bactericidal in a mouse model of Acinetobacter baumannii infection. Structural analyses of novel inhibitors explain differences in biochemical and whole-cell activity across bacterial clades and underscore why this discovery may have broad translational impact on treatment of the most recalcitrant bacterial infections.

Translational Regulation of Duplicated Gene Expression Evolution in Allopolyploid Cotton.

Polyploidy, a prevalent event in plant evolution, drives phenotypic diversification and speciation. While transcriptional changes and regulation in polyploids have been extensively studied, the translational level impact remains largely unexplored. To address this gap, we conducted a comparative transcriptomic and translatomic analysis of cotton leaves from allopolyploid species G. hirsutum (AD1) and G. barbadense (AD2) relative to their model A-genome and D-genome diploid progenitors. Our data revealed that while allopolyploidization significantly affects the transcriptional landscape, its impact on translation was relatively modest, evidenced by a narrower expression range and fewer expression changes in ribosome-protected fragments than in mRNA levels. Allopolyploid-specific changes commonly identified in both AD1 and AD2 were observed in 7393 genes at either transcriptional or translational levels. Interestingly, the majority of translational changes exhibited concordant down-regulation in both ribosome-protected fragments and mRNA, particularly associated with terpenoid synthesis and metabolism (352 genes). Regarding translational efficiency (TE), at least one-fifth of cotton genes exhibit translational level regulation, with a general trend of more down-regulation (13.9-15.1%) than up-regulation (7.3-11.2%) of TE. The magnitude of translational regulation was slightly reduced in allopolyploids compared with diploids, and allopolyploidy tends to have a more profound impact on genes and functional associations with ultra-low TE. Moreover, we demonstrated a reduced extent of homeolog expression biases during translation compared with transcription. Our study provides insights into the regulatory consequences of allopolyploidy post-transcription, contributing to a comprehensive understanding of regulatory mechanisms of duplicated gene expression evolution.

Driving Deployment of Bioengineered Products-An Arduous, Sometimes Tedious, Challenging, Rewarding, Most Exciting Journey That Has to Be Made!

More than three decades ago, we embarked on a number of bioengineering explorations using the most advanced materials and fabrication methods. In every area we ventured into, it was our intention to ensure fundamental discoveries were deployed into the clinic to benefit patients. When we embarked on this journey, we did so without a road map, not even a compass, and so the path was arduous, sometimes tedious. Now, we can see the doorway to deployment on the near horizon. We now appreciate that overcoming the challenges has made this a rewarding and exciting journey. However, maybe we could have been here a lot sooner, and so maybe the lessons we have learned could benefit others and accelerate progress in clinical translation. Through a number of case studies, including neural regeneration, cartilage regeneration, skin regeneration, the 3D printing of capsules for islet cell transplantation, and the bioengineered cornea, here, we retrace our steps. We will summarise the journey to date, point out the obstacles encountered, and celebrate the translational impact. Then, we will provide a framework for project design with the clinical deployment of bioengineered products as the goal.

A literature review of genetics and epigenetics of HCV-related hepatocellular carcinoma: translational impact.

Hepatocellular carcinoma (HCC) poses a significant global health burden and ranks as the fifth most prevalent cancer on a global scale. Hepatitis C virus (HCV) infection remains one of the major risk factors for HCC development. HCC is a heterogeneous disease, and the development of HCC caused by HCV is intricate and involves various factors, including genetic susceptibility, viral factors, immune response due to chronic inflammation, alcohol abuse, and metabolic dysfunction associated with fatty liver disease. In this review, we provide a comprehensive and updated review of research on the genetics and epigenetic mechanisms implicated in developing HCC associated with HCV infection. We also discuss the potential translational implications, including novel biomarkers and drugs for treatment. A comprehensive literature search was conducted in June 2023 in PubMed and Embase databases. Recent findings indicate that a variety of genetic and epigenetic processes are involved in the pathogenesis and continue to exist even after the complete elimination of HCV. The deregulation of the epigenome has been identified as a significant factor in the deletrious effects of liver disease, especially during the initial stages when genetic alterations are uncommon. The enduring "epigenetic memory" of gene expression is believed to be regulated by epigenetic mechanisms, indicating that alterations caused by HCV infection continue to exist and are linked to the risk of development of liver cancer even after successful treatment. Systems biology analytical methods will be required to delineate the magnitude and significance of both genetic and epigenomic alterations in tumor evolution. By facilitating a more profound understanding of these aspects, this will ultimately foster the advancement of novel therapies and ultimately improve outcomes for patients.

The Chilean exposome-based system for ecosystems (CHiESS): a framework for national data integration and analytics platform.

The double burden of diseases and scarce resources in developing countries highlight the need to change the conceptualization of health problems and translational research. Contrary to the traditional paradigm focused on genetics, the exposome paradigm proposed in 2005 that complements the genome is an innovative theory. It involves a holistic approach to understanding the complexity of the interactions between the human being’s environment throughout their life and health. This paper outlines a scalable framework for exposome research, integrating diverse data sources for comprehensive public health surveillance and policy support. The Chilean exposome-based system for ecosystems (CHiESS) project proposes a conceptual model based on the ecological and One Health approaches, and the development of a technological dynamic platform for exposome research, which leverages available administrative data routinely collected by national agencies, in clinical records, and by biobanks. CHiESS considers a multilevel exposure for exposome operationalization, including the ecosystem, community, population, and individual levels. CHiESS will include four consecutive stages for development into an informatic platform: (1) environmental data integration and harmonization system, (2) clinical and omics data integration, (3) advanced analytical algorithm development, and (4) visualization interface development and targeted population-based cohort recruitment. The CHiESS platform aims to integrate and harmonize available secondary administrative data and provide a complete geospatial mapping of the external exposome. Additionally, it aims to analyze complex interactions between environmental stressors of the ecosystem and molecular processes of the human being and their effect on human health. Moreover, by identifying exposome-based hotspots, CHiESS allows the targeted and efficient recruitment of population-based cohorts for translational research and impact evaluation. Utilizing advanced technologies such as Artificial Intelligence (AI), Internet of Things (IoT), and blockchain, this framework enhances data security, real-time monitoring, and predictive analytics. The CHiESS model is adaptable for international use, promoting global health collaboration and supporting sustainable development goals.

Development and Evaluation of Docetaxel-Loaded Nanostructured Lipid Carriers for Skin Cancer Therapy.

This study focuses on the design, characterization, and optimization of nanostructured lipid carriers (NLCs) loaded with docetaxel for the treatment of skin cancer. Employing a systematic formulation development process guided by Design of Experiments (DoE) principles, key parameters such as particle size, polydispersity index (PDI), zeta potential, and entrapment efficiency were optimized to ensure the stability and drug-loading efficacy of the NLCs. Combined XRD and cryo-TEM analysis were employed for NLC nanostructure evaluation, confirming the formation of well-defined nanostructures. In vitro kinetics studies demonstrated controlled and sustained docetaxel release over 48 h, emphasizing the potential for prolonged therapeutic effects. Cytotoxicity assays on human umbilical vein endothelial cells (HUVEC) and SK-MEL-24 melanoma cell line revealed enhanced efficacy against cancer cells, with significant selective cytotoxicity and minimal impact on normal cells. This multidimensional approach, encompassing formulation optimization and comprehensive characterization, positions the docetaxel-loaded NLCs as promising candidates for advanced skin cancer therapy. The findings underscore the potential translational impact of these nanocarriers, paving the way for future preclinical investigations and clinical applications in skin cancer treatment.

Advancements and Impact of Medical Translation During the Golden Age: A Comprehensive Analysis

This article presents a comprehensive analysis of the advancements and impact of medical translation during the Golden Age of Translation. It focuses on the fundamental role that translators and scholars played in disseminating medical knowledge, shaping medical practices, and fostering intellectual and cultural exchange. It also discusses the significance of the House of Wisdom in Baghdad, key translators and their contributions, as well as the influence of translated medical texts such as Avicenna's Canon of Medicine, Al-Razi's Book of Healing, and Al-Zahrawi's Comprehensive Book on Medicine. Also examined is the impact of translation on the standardization of medical terminology and the transmission of medical knowledge across cultures and regions. The article concludes by highlighting the lasting legacy of translations in terms of their impact on global medical knowledge and suggests possible areas in which to conduct further research on medical translation history, as well as the role of modern technology in understanding and interpreting historical medical texts.

A novel minimally invasive and versatile kyphoplasty balloon-based model of porcine spinal cord injury.

Spinal cord injury (SCI) animal models often utilize an open surgical laminectomy, which results in animal morbidity and also leads to changes in spinal canal diameter, spinal cord perfusion, cerebrospinal fluid flow dynamics, and spinal stability which may confound SCI research. Moreover, the use of open surgical laminectomy for injury creation lacks realism when considering human SCI scenarios. We developed a novel, image-guided, minimally invasive, large animal model of SCI which utilizes a kyphoplasty balloon inserted into the epidural space via an interlaminar approach without the need for open surgery. The model was validated in 5 Yucatán pigs with imaging, neurofunctional, histologic, and electrophysiologic findings consistent with a mild compression injury. Few large animal models exist that have the potential to reproduce the mechanisms of spinal cord injury (SCI) commonly seen in humans, which in turn limits the relevance and applicability of SCI translational research. SCI research relies heavily on animal models, which typically involve an open surgical, dorsal laminectomy which is inherently invasive and may have untoward consequences on animal morbidity and spinal physiology that limit translational impact. We developed a minimally invasive, large animal model of spinal cord injury which utilizes a kyphoplasty balloon inserted percutaneously into the spinal epidural space. Balloon inflation results in a targeted, compressive spinal cord injury with histological and electrophysiological features directly relevant to human spinal cord injury cases without the need for invasive surgery. Balloon inflation pressure, length of time that balloon remains inflated, and speed of inflation may be modified to achieve variations in injury severity and subtype.

Anything goes for participant, patient and public involvement in youth mental health research

AbstractBackgroundParticipant and Public Involvement in youth mental health research aims at making research more responsive to the needs of youth struggling with mental health issues, their parents, and mental health professionals and other stakeholders. Do characteristics of Patient and Public Involvement (PPI) in youth mental health research align with transparency and replication prerequisites as necessary conditions for translation? Relatedly, the question is addressed whether co‐authorship should be assigned to youth involved in the study.MethodsHere we address these questions re‐visiting 50 PPI studies included in two recent systematic reviews of PPI on characteristics that are pertinent to questions about transparency, replicability, translatability, and co‐authorship in PPI research.ResultsAlmost two‐third of the studies on youth mental health incorporating PPI translate their results to policy or practice, mostly as recommendations but sometimes also by dissemination of (online) interventions. At the same time the authors of a substantial majority of the studies (70%) also suggest the need for further work on their results, for example, in randomized controlled trials to validate the outcome of their exploratory inquiry. Only a quarter of the studies using PPI met the conditions for replicability, thus a majority of the PPI studies suggest premature translation of results. Authorship to involved participants was assigned in 24% of the studies.Conclusions“Anything goes” for PPI in an exploratory stage to generate fruitful hypotheses. Translation of the findings of PPI studies however require a firm evidence base of replicated results. Radical merging of research and action in participatory action research seems incompatible with replicable and therefore translatable inquiry. Assigning co‐authorship to PPI representatives is often at odds with current guidelines for authorship. More evidence from randomized trials on the translational impact of PPI is needed before grant foundations should require PPI in grant proposals.

Ocherk istorii razvitiya teorii perevoda

This article analyzes the characteristics and influences of translation theory in different historical periods in both Chinese and Western contexts and explores the significant impact of Soviet literature translation on Chinese translation practice and theoretical development.