Developing neuro-oncology clinical trials in low- and middle-income countries: a scoping review of the current literature.

Low- and middle-income countries (LMICs) have historically been under-represented in clinical trials, leading to a disparity in evidence-based recommendations for the management of neurooncological conditions. To address this knowledge gap, we conducted a scoping review to assess the current literature on clinical trials in neuro-oncology from LMICs. The eligibility criteria for inclusion in this review included clinical trials registered and conducted with human subjects, with available English language text or translation, and focussed on neuro-oncological cases. The literature search strategy captured 408 articles, of which 61 met these criteria, with a significant number of randomised controlled trials from specific LMICs. The review found that LMIC clinical trials have contributed significantly to understanding surgical, chemotherapeutic, and radiation therapy interventions for brain tumours, paediatric cancers, and the repurposing of drugs as new targets in neuro-oncology. These findings highlight the potential for expanding clinical trials research in neuro-oncology in LMICs, which may significantly impact global understanding and management of these conditions, particularly from diverse populations from the global south.

EXPRESS: Translational Science and Related Disciplines.

Translational research moves scientific discoveries and innovations across the development spectrum for a particular target or disease, trying to bridge in a multidisciplinary fashion the gap between laboratory scientific discoveries and practical, real-world applications in medicine and in healthcare. Translational research aims to move research findings across settings, specific languages, methodologies and study designs, from laboratory to clinical practice and ultimately into community and population-level health benefits.In contrast, translational science is a distinct field, which evolved over time towards a systematic study and practice of operationalizing the translation of content from one language, ecosystem, environment, contextual landscape, culture, discipline, area or domain into another. It involves systematic and transdisciplinary integration of knowledge from basic science, clinical research and population science to improve human health, better longevity and to ensure disease and disability free lives. Translational science often uses knowledge, operational frameworks and specific capabilities borrowed from other specialties, disciplines and fields such as operations management, implementation and dissemination science, quality improvement and management, project management, public health, intervention science, change management and leadership, decision science, design thinking, functional design, data science, communication and marketing science, etc.The main goal of this article is to open a series of thematic reviews in this journal, introducing the reader to the main definitions, contingencies, touchpoints and overlapping areas between translational science and these related specialties, disciplines and fields of study. Transdisciplinary capabilities borrowing from these related specialties can create a robust translational science machinery for health systems, research organizations and innovation hubs.

Canadian beach cohort study: protocol of a prospective study to assess the burden of recreational water illness.

BACKGROUND: Recreational water activities at beaches are popular among Canadians. However, these activities can increase the risk of recreational water illnesses (RWI) among beachgoers. Few studies have been conducted in Canada to determine the risk of these illnesses. This protocol describes the methodology for a study to determine the risk and burden of RWI due to exposure to fecal pollution at beaches in Canada. METHODS: This study will use a mixed-methods approach, consisting of a prospective cohort study of beachgoers with embedded qualitative research. The cohort study involves recruiting and enrolling participants at public beaches across Canada, ascertaining their water and sand contact exposure status, then following-up after seven days to determine the incidence of acute RWI outcomes. We will test beach water samples each recruitment day for culture-based E. coli, enterococci using rapid molecular methods, and microbial source tracking biomarkers. The study started in 2023 and will continue to 2025 at beaches in British Columbia, Manitoba, Ontario, and Nova Scotia. The target enrollment is 5000 beachgoers. Multilevel logistic regression models will be fitted to examine the relationships between water and sand contact and RWI among beachgoers. We will also examine differences in risks by beachgoer age, gender, and beach location and the influence of fecal indicator bacteria and other water quality parameters on these relationships. Sensitivity analyses will be conducted to examine the impact of various alternative exposure and outcome definitions on these associations. The qualitative research phase will include focus groups with beachgoers and key informant interviews to provide additional contextual insights into the study findings. The study will use an integrated knowledge translation approach. DISCUSSION: Initial implementation of the study at two Toronto, Ontario, beaches in 2023 confirmed that recruitment is feasible and that a high completion rate (80%) can be achieved for the follow-up survey. While recall bias could be a concern for the self-reported RWI outcomes, we will examine the impact of this bias in a negative control analysis. Study findings will inform future recreational water quality guidelines, policies, and risk communication strategies in Canada.

Genome-wide analysis reveals transcriptional and translational changes during diapause of the Asian corn borer (Ostrinia furnacalis).

BACKGROUND: Diapause, a pivotal phase in the insect life cycle, enables survival during harsh environmental conditions. Unraveling the gene expression profiles of the diapause process helps uncover the molecular mechanisms that underlying diapause, which is crucial for understanding physiological adaptations. In this study, we utilize RNA-seq and Ribo-seq data to examine differentially expressed genes (DEGs) and translational efficiency during diapause of Asian corn borer (Ostrinia furnacalis, ACB). RESULTS: Our results unveil genes classified as "forwarded", "exclusive", "intensified", or "buffered" during diapause, shedding light on their transcription and translation regulation patterns. Furthermore, we explore the landscape of lncRNAs (long non-coding RNAs) during diapause and identify differentially expressed lncRNAs, suggesting their roles in diapause regulation. Comparative analysis of different types of diapause in insects uncovers shared and unique KEGG pathways. While shared pathways highlight energy balance, exclusive pathways in the ACB larvae indicate insect-specific adaptations related to nutrient utilization and stress response. Interestingly, our study also reveals dynamic changes in the HSP70 gene family and proteasome pathway during diapause. Manipulating HSP protein levels and proteasome pathway by HSP activator or inhibitor and proteasome inhibitor affects diapause, indicating their vital role in the process. CONCLUSIONS: In summary, these findings enhance our knowledge of how insects navigate challenging conditions through intricate molecular mechanisms.

Cross-cultural adaptation and validation to Brazilian Portuguese of the 'knowledge of gestational diabetes (GDM)' questionnaire for women with GDM.

BACKGROUND: Gestational diabetes mellitus (GDM) is characterized by hyperglycemia during pregnancy. There are many diabetes-specific tools for collecting information validated in Brazilian Portuguese. However, there are no specific instruments to assess knowledge about GDM in Brazilian Portuguese. The aim of this study was to cross-culturally adapt and validate the Brazilian Portuguese version of the Knowledge of Gestational Diabetes Mellitus questionnaire (GDMKQ). METHODS: This study was conducted in southern Brazil from January to December 2023. Women with GDM or diabetes identified during pregnancy were considered eligible based on specific criteria. Clinical and demographic data were obtained through a medical records search. The GDMKQ underwent a multistep adaptation process, including translation, back-translation, content validity assessment, and cognitive interviews. After administration to participants, internal consistency, item-total correlation, and intraclass correlation were assessed. Confirmatory factor analysis was also conducted to ensure validity. RESULTS: A total of 155 pregnant women were recruited for the study. Most participants were aged 18-30 years, and hypertension was the main comorbidity (25.2%). Regarding education, most participants (58.7%) attended high school. The Brazilian Portuguese version of the GDMKQ consisted of 32 items. The intraclass correlation was established by two independent interviews with 57 participants, yielding a correlation coefficient of 0.79 (p < 0.01). Internal consistency (Cronbach's alpha) was 0.81 overall but was less than 0.7 for each domain. Item-total correlations were calculated, and confirmatory factor analysis indicated a good model fit. The final Brazilian Portuguese version of the questionnaire consisted of 32 items. CONCLUSIONS: The Brazilian Portuguese version of the GDMKQ yielded a reliable and valid tool for evaluating diabetes knowledge in pregnant women.

MicroRNAs and therapeutic potentials in acute and chronic cardiac disease.

microRNAs (miRNAs) are small regulatory RNAs implicated in various cardiac disorders. In this review, the role of miRNAs is discussed in relation to acute myocardial infarction and chronic heart failure. In both settings, miRNAs are altered, contributing to injury and adverse remodeling. Notably, miRNA profiles differ between acute ischemic injury and progressive heart failure. Owing to miRNA variabilities between disease stages and delivery difficulties, translation of animal studies to the clinic remains challenging. The identification of distinct miRNA signatures could lead to the development of miRNA therapies tailored to different disease stages. Here, we summarize the current understanding of miRNAs in acute and chronic cardiac diseases, identify knowledge gaps and discuss progress in developing miRNA-based treatment strategies.

Sex-specific molecular signature of mouse podocytes in homeostasis and in response to pharmacological challenge with rapamycin.

BACKGROUND: Sex differences exist in the prevalence and progression of major glomerular diseases. Podocytes are the essential cell-type in the kidney which maintain the physiological blood-urine barrier, and pathological changes in podocyte homeostasis are critical accelerators of impairment of kidney function. However, sex-specific molecular signatures of podocytes under physiological and stress conditions remain unknown. This work aimed at identifying sexual dimorphic molecular signatures of podocytes under physiological condition and pharmacologically challenged homeostasis with mechanistic target of rapamycin (mTOR) inhibition. mTOR is a crucial regulator involved in a variety of physiological and pathological stress responses in the kidney and inhibition of this pathway may therefore serve as a general stress challenger to get fundamental insights into sex differences in podocytes. METHODS: The genomic ROSAmT/mG-NPHS2 Cre mouse model was used which allows obtaining highly pure podocyte fractions for cell-specific molecular analyses, and vehicle or pharmacologic treatment with the mTOR inhibitor rapamycin was performed for 3 weeks. Subsequently, deep RNA sequencing and proteomics were performed of the isolated podocytes to identify intrinsic sex differences. Studies were supplemented with metabolomics from kidney cortex tissues. RESULTS: Although kidney function and morphology remained normal in all experimental groups, RNA sequencing, proteomics and metabolomics revealed strong intrinsic sex differences in the expression levels of mitochondrial, translation and structural transcripts, protein abundances and regulation of metabolic pathways. Interestingly, rapamycin abolished prominent sex-specific clustering of podocyte gene expression and induced major changes only in male transcriptome. Several sex-biased transcription factors could be identified as possible upstream regulators of these sexually dimorphic responses. Concordant to transcriptomics, metabolomic changes were more prominent in males. Remarkably, high number of previously reported kidney disease genes showed intrinsic sexual dimorphism and/or different response patterns towards mTOR inhibition. CONCLUSIONS: Our results highlight remarkable intrinsic sex-differences and sex-specific response patterns towards pharmacological challenged podocyte homeostasis which might fundamentally contribute to sex differences in kidney disease susceptibilities and progression. This work provides rationale and an in-depth database for novel targets to be tested in specific kidney disease models to advance with sex-specific treatment strategies.

The global burden of chronic kidney diseases is rapidly increasing and is projected to become the fifth most common cause of years of life lost worldwide by 2040. Sexual dimorphism in kidney diseases and transplantation is well known, yet sex-specific therapeutic strategies are still missing. One reason is the lack of knowledge due to the lack of inclusion of sex as a biological variable in study designs. This work aimed at identification of molecular signatures of male and female podocytes, gate-keepers of the glomerular filtration barrier. Like cardiomyocytes, podocytes are terminally differentiated cells which are highly susceptible towards pathological challenges. Podocytes are the decisive cell-type of the kidney to maintain the physiological blood-urine barrier, and disturbances of their homeostasis critically accelerate kidney function impairment. By help of a genomic mouse model, highly purified podocytes were obtained from male and female mice with and without pharmacological challenge of the mechanistic target of rapamycin (mTOR) signaling pathway which is known to be deregulated in major kidney diseases. Deep RNA sequencing, proteomics and metabolomics revealed strong intrinsic sex differences in the expression levels of mitochondrial, translation and structural transcripts, protein abundances and regulation of metabolic pathways which might fundamentally contribute to sex differences in kidney disease susceptibilities and progression. Remarkably, high number of previously reported kidney disease genes showed so far unknown intrinsic sexual dimorphism and/or different response patterns towards mTOR inhibition. Our work provides an in-depth database for novel targets to be tested in kidney disease models to advance with sex-specific treatment strategies.

Viral Factors in Modulation of Host Immune Response: A Route to Novel Antiviral Agents and New Therapeutic Approaches.

Viruses utilize host cells at all stages of their life cycle, from the transcription of genes and translation of viral proteins to the release of viral copies. The human immune system counteracts viruses through a variety of complex mechanisms, including both innate and adaptive components. Viruses have an ability to evade different components of the immune system and affect them, leading to disruption. This review covers contemporary knowledge about the virus-induced complex interplay of molecular interactions, including regulation of transcription and translation in host cells resulting in the modulation of immune system functions. Thorough investigation of molecular mechanisms and signaling pathways that are involved in modulating of host immune response to viral infections can help to develop novel approaches for antiviral therapy. In this review, we consider new therapeutic approaches for antiviral treatment. Modern therapeutic strategies for the treatment and cure of human immunodeficiency virus (HIV) are considered in detail because HIV is a unique example of a virus that leads to host T lymphocyte deregulation and significant modulation of the host immune response. Furthermore, peculiarities of some promising novel agents for the treatment of various viral infections are described.

Psychological Interventions and Those With Elements of Positive Psychology for Child and Youth Mental Health During the COVID-19 Pandemic: Literature Review, Lessons Learned, and Areas for Future Knowledge Dissemination.

BACKGROUND: There was a marked decline in child and teenage mental health worldwide during the pandemic, with increasing prevalence of depression, anxiety, and suicide. Research indicates that positive psychological interventions may be beneficial for mental health. OBJECTIVE: The aims of this review were to evaluate positive psychological interventions for child and youth mental health implemented during the COVID-19 pandemic and assess overall effectiveness for mental health and knowledge. METHODS: We undertook a literature search of PubMed, MEDLINE, and Google Scholar for all eligible studies on digital and hybrid in-person psychological interventions for youth mental health during the COVID-19 pandemic. A particular emphasis was placed on positive psychological interventions or interventions that had components of positive psychology, including gratitude, acceptance, positive emotions, or resilience building. RESULTS: A total of 41 interventions were included in this review. Most of the interventions were digital. Overall, most of the interventions assisted with one or more mental health or psychological indicators, such as depression, anxiety, posttraumatic stress disorder, stress, and resilience. However, findings were mixed when it came to targeting both depression and anxiety together. The interventions that promoted youth mental health most often had a range of diverse positive psychology components and were evidence based. Not all studies measured changes in mindfulness. Few studies examined knowledge acquired on mental health self-care, managing mental health problems, knowledge of positive psychological techniques, mindfulness knowledge, or mental health self-efficacy. CONCLUSIONS: Diverse multicomponent interventions appear to assist with youth mental health overall, although their effects on both depression and anxiety are less clear. There is also a need for more research on knowledge gains to determine whether the interventions improved knowledge on mental health-supportive behaviors, which may be sustained beyond the intervention. Finally, more studies need to evaluate whether the interventions assisted with increasing self-efficacy for practicing positive psychological techniques as well as changes in mindfulness levels. Future studies should not only assess effectiveness for mental health outcomes but also assess knowledge translation, with valid measures of knowledge and self-efficacy for mental health-supportive behaviors and positive psychological skills acquired (eg, the ability to practice mindfulness).

MobiTangibles: Enabling Physical Manipulation Experiences of Virtual Precision Hand-held Tools' Miniature Control in VR.

Realistic simulation for miniature control interactions, typically identified by precise and confined motions, commonly found in precision hand-held tools, like calipers, powered engravers, retractable knives, etc., are beneficial for skill training associated with these kinds of tools in virtual reality (VR) environments. However, existing approaches aiming to simulate hand-held tools' miniature control manipulation experiences in VR entail prototyping complexity and require expertise, posing challenges for novice users and individuals with limited resources. Addressing this challenge, we introduce MobiTangibles-proxies for precision hand-held tools' miniature control interactions utilizing smartphone-based magnetic field sensing. MobiTangibles passively replicate fundamental miniature control experiences associated with hand-held tools, such as single-axis translation and rotation, enabling quick and easy use for diverse VR scenarios without requiring extensive technical knowledge. We conducted a comprehensive technical evaluation to validate the functionality of MobiTangibles across diverse settings, including evaluations for electromagnetic interference within indoor environments. In a user-centric evaluation involving 15 participants across bare hands, VR controllers, and MobiTangibles conditions, we further assessed the quality of miniaturized manipulation experiences in VR. Our findings indicate that MobiTangibles outperformed conventional methods in realism and fatigue, receiving positive feedback.

Future of Team-based Basic and Translational Science in Radiation Oncology.

To further optimize radiotherapy, a more personalized treatment towards individual patient's risk profiles, dissecting both patient-specific tumor and normal tissue response to multimodality treatments is needed. Novel developments in radiobiology, using in vitro patient-specific complex tissue resembling 3D models and multiomics approaches at a spatial single-cell level, may provide unprecedented insight into the radiation responses of tumors and normal tissue. Here, we describe the necessary team effort, including all disciplines in radiation oncology, to integrate such data into clinical prediction models and link the relatively "big data" from the clinical practice, allowing accurate patient stratification for personalized treatment approaches.

Looking back to look forward in applying evidence and science for health emergencies: A rapid response program for COVID-19 clinical management

A public health emergency provides an opportunity and need to utilize the power of evidence, science, research and innovation, and practicality to provide rapid solutions. The COVID-19 pandemic did exactly that. It challenged the scientific and public health community from identification to tracking the virus, from characterizing the disease to developing strategies to treat and contain the pathogen. The Pan American Health Organization (PAHO), as an international public health agency working in the region of the Americas, responded to these challenges with extreme vitality, transparency and accountability, and many achievements were made. The PAHO clinical management team put into practice a rapid response program to support evidence-informed decision making (EIDM) in the Region, and in Member States.

Evidências para a Promoção da Saúde no Brasil: relato de um serviço de resposta rápida / Evidence for Health Promotion in Brazil: report on a rapid response service / Evidencia para la promoción de la salud en Brasil: informe sobre un servicio de respuesta rápida

[RESUMO]. Objetivo. Apresentar a experiência de um serviço de resposta rápida para apoiar a tomada de decisão em saúde. Método. São descritos os processos e resultados de um serviço de produção de revisões rápidas e mapas de evidências para apoiar a tomada de decisão no âmbito da Política Nacional de Promoção da Saúde, bem como a percepção dos autores sobre o processo de trabalho. Resultados. O serviço de resposta rápida teve início em 2020. Até dezembro de 2023, foram produzidas 54 revisões rápidas e cinco mapas de evidências, abrangendo nove temáticas de Promoção da Saúde. Estes produtos foram desenvolvidos em quatorze etapas por uma equipe composta por coordenador, supervisoras, revisores e bibliotecária. O desenvolvimento das respostas rápidas se configurou um processo de tradução do conhecimento e envolveu a interação contínua entre as equipes demandantes e de produção. O estabelecimento de comunicação efetiva foi um fator crítico para que os produtos fossem entregues em tempo oportuno e alinhados às necessidades dos tomadores de decisão e seus apoiadores. Conclusão. Os serviços de resposta rápida podem contribuir para melhorar o uso de evidências na tomada de decisão nas políticas e sistemas de saúde.

[ABSTRACT]. Objective. Present the experience of a rapid response service to support decision-making in health systems. Methodology. Description of the processes and results of a service that produces rapid reviews and evidence maps to support decision-making under the National Health Promotion Policy, as well as the authors' perception of the work process. Results. The rapid response service started in 2020. By December 2023, 54 rapid reviews and five evidence maps had been produced, covering nine health promotion topics. These products were developed in 14 stages by a team made up of a coordinator, supervisors, proofreaders, and a librarian. The development of rapid responses involved a knowledge translation process, with continuous interactions between the requesting teams and production teams. Establishing effective communication was a critical factor in delivering products on time and in line with the needs of decision-makers and their supporters. Conclusion. Rapid response services can help improve the use of evidence for decision-making in health policies and health systems.

[RESUMEN]. Objetivo. Presentación de la experiencia de un servicio de respuesta rápida para brindar apoyo a la toma de decisiones en materia de salud. Método. Se describen los procesos y resultados de un servicio de elaboración de revisiones rápidas y mapas de evidencia para brindar apoyo a la toma de decisiones en el marco de la Política Nacional de Promoción de la Salud, así como la percepción de los autores sobre el proceso de trabajo. Resultados. El servicio de respuesta rápida se inició en el 2020. Hasta diciembre del 2023, se habían elaborado 54 revisiones rápidas y cinco mapas de evidencia, que abarcaban nueve temas de promoción de la salud. Estos productos fueron elaborados en 14 etapas por un equipo formado por un coordinador, varios supervisores y revisores y un bibliotecario. La elaboración de respuestas rápidas fue un proceso de traducción del conocimiento e implicó una interacción continua entre los equipos solicitantes y el equipo de elaboración. El establecimiento de una comunicación eficaz fue un factor decisivo para entregar los productos a tiempo y en consonancia con las necesidades de los responsables de la toma de decisiones y su personal de apoyo. Conclusión. Los servicios de respuesta rápida pueden ayudar a mejorar el uso de evidencia en la toma de decisiones relacionadas con las políticas y los sistemas de salud.

Inverse kinematics in cervical spine models: Effects of scaling and model degrees of freedom for extension and flexion movements.

Intervertebral kinematics can affect model-predicted loads and strains in the spine; therefore knowledge of expected vertebral kinematics error is important for understanding the limitations of model predictions. This study addressed how different kinematic models of the neck affect the prediction of intervertebral kinematics from markers on the head and trunk. Eight subjects executed head and neck extension-flexion motion with simultaneous motion capture and biplanar dynamic stereo-radiography (DSX) of vertebrae C1-C7. A generic head and neck model in OpenSim was scaled by marker data, and three versions of the model were used with an inverse kinematics solver. The models differed according to the number of independent degrees of freedom (DOF) between the head and trunk: 3 rotational DOF with constraints defining intervertebral kinematics as a function of overall head-trunk motion; 24DOF with 3 independent rotational DOF at each level, skull-T1; 48DOF with 3 rotational and 3 translational DOF at each level. Marker tracking error was lower for scaled models compared to generic models and decreased as model DOF increased. The largest mean absolute error (MAE) was found in extension-flexion angle and anterior-posterior translation at C1-C2, and superior-inferior translation at C2-C3. Model scaling and complexity did not have a statistically significant effect on most error metrics when corrected for multiple comparisons, but ranges of motion were significantly different from DSX in some cases. This study evaluated model kinematics in comparison to gold standard radiographic data and provides important information about intervertebral kinematics error that are foundational to model validity.

Strengthening Clinician-Researchers' Communication and Knowledge Translation Skills: An Innovative Game Model From the Breathe Well Group.

Communication is a core component of a clinician's role; however, when clinicians conduct research, communicating the emerging findings and recommendations to different types of stakeholders can be unfamiliar territory. Communicating research to advocate for change can be even more challenging. Clinician researchers seeking to be agents for change need to conceive and craft specific, evidence-based messages and communicate these effectively to different stakeholders to negotiate action. As part of a global health research program, we developed and tested a novel game-based model to strengthen the communication skills of clinician researchers, from 4 countries, for improving services for chronic obstructive pulmonary disease. This model focused on communication with 3 key stakeholder groups for knowledge translation: Patients/carers, healthcare providers and policy makers/healthcare managers. Delivered through a series of facilitated, online meetings, this model consisted of 2 parts: developing and rehearsing advocacy messages with coaching support, and then testing them with a panel of 3 representative stakeholders, and an audience of fellow researchers. All the country teams reported increased confidence in crafting advocacy messages for specific stakeholders and have applied lessons learned from the model. Delivering this model within a global health research program requires mentoring, time, commitment, resources and translation support to address language barriers. It offers an exemplar to build the communication skills of clinician and non-clinician researchers so that they can go beyond dissemination toward translation of evidence into policy and practice.

Treating with minerals in the Middle Ages: the rare substance mumiya' (pitch-asphalt) and its medicinal uses in Byzantium.

Premodern medicine used a variety of mineral substances for therapeutic purposes. The present article deals with pitch-asphalt, and, in particular, a precious kind of it called mumiya' originating in Persia. It was first described in detail in the Arabic pharmacological tradition, and its fame spread throughout the medieval Mediterranean, including Byzantium. By editing and examining for the first time a previously unexplored medieval Greek text on mumiya', this study offers new insights into the medicinal uses of this substance. It also significantly increases our understanding of the intense cross-cultural transfer of medical knowledge from the Islamicate world to Byzantium by showing that this was not merely based on the translation of a few Arabic medical works into Greek, but was a multifaceted phenomenon involving a complex nexus of sources that require further investigation.

Measuring the quality of self-care of elderly patients with dementia in a developing country.

In developing countries like Uganda, people with dementia are cared for by non-medically trained family members with minimal support from the formal healthcare system. The quality of care in this setting is largely unknown but significantly affects the well-being of those with dementia. A tool designed to measure the quality of informal care for old frail adults with or without dementia was translated into Luganda. A committee of experts reviewed and finalized the translation, which was pilot-tested and then used to measure the quality of dementia self-care. We consecutively enrolled 105 caregivers of elderly people with dementia; the median age was 35 years (Interquartile Range 26-47 years), and 67% were females, taking care of a grandparent (44%) or a parent (34%). We used confirmatory factor analysis to assess for structural validity and computed correlation coefficients and Cronbach's alpha to assess for discriminant validity and internal reliability, respectively. The three-factor model applied to the 20 items, adequately fit the data (Comparative Fit Index = 0.88, Tucker-Lewis Index = 0.87, Root Mean Square Error of Approximation = 0.08; 90% Confidence Interval (0.06-0.09), Standardized Root Mean Square Residual = 0.089). There was good discriminant validity, and correlation coefficients between dimensions/scales and the Dementia Knowledge Assessment Scale scores were low. There was good internal reliability with all items Cronbach's alpha ranging from 0.69 to 0.89. Our findings demonstrated that this culturally adapted, shorter measurement tool is valid and reliable. The tool can be used by researchers, health workers, and agencies to assess the quality of self-care for elderly people with dementia in Uganda.

Domain-knowledge enabled ensemble learning of 5-formylcytosine (f5C) modification sites.

5-formylcytidine (f5C) is a unique post-transcriptional RNA modification found in mRNA and tRNA at the wobble site, playing a crucial role in mitochondrial protein synthesis and potentially contributing to the regulation of translation. Recent studies have unveiled that the f5C modifications may drive mitochondrial mRNA translation to power cancer metastasis. Accurate identification of f5C sites is essential for further unraveling their molecular functions and regulatory mechanisms, but there are currently no computational methods available for predicting their locations. In this study, we introduce an innovative ensemble approach, successfully enabling the computational recognition of Saccharomyces cerevisiae f5C. We conducted a comprehensive model selection process that involved multiple basic machine learning and deep learning algorithms such as recurrent neural networks, convolutional neural networks and Transformer-based models. Initially trained only on sequence information, these individual models achieved an AUROC ranging from 0.7104 to 0.7492. Through the integration of 32 novel domain-derived genomic features, the performance of individual models has significantly improved to an AUROC between 0.7309 and 0.8076. To further enhance accuracy and robustness, we then constructed the ensembles of these individual models with different combinations. The best performance attained by our ensemble models reached an AUROC of 0.8391. Shapley additive explanations were conducted to explain the significant contributions of genomic features, providing insights into the putative distribution of f5C across various topological regions and potentially paving the way for revealing their functional relevance within distinct genomic contexts. A freely accessible web server that allows real-time analysis of user-uploaded sites can be accessed at: www.rnamd.org/Resf5C-Pred.

Canadian Veterans' Experiences of Living with Chronic Pain: A Descriptive Qualitative Study.

Background: An estimated 30% of veterans live with chronic pain, compared to 20% of Canadians in the general population. Veterans face health care challenges upon release from the military, increasing difficulties in obtaining chronic pain care. Aims: We explored experiences of Canadian Armed Forces veterans living with chronic pain, their transition from military to civilian care, perceived barriers and facilitators to chronic pain care, and impacts of their pain on the domains of well-being. Methods: We conducted a qualitative descriptive study using semistructured interviews. We used a deductive/inductive approach to derive themes and concepts from interview transcripts. Results: Thirty-five veterans living with chronic pain participated. Participants reported that pain affected their lives in numerous ways, including negatively impacting relationships and limiting activities of daily living and leisure. They identified barriers to care, including lack of access to family doctors or health care services, reluctance to ask for help, and challenges in obtaining coverage for services from Veterans Affairs Canada. Facilitators included support from other veterans and online resources. Chronic pain had bidirectional effects on domains of well-being. Conclusions: Experiences of pain varied among Canadian veterans, and military culture played a role in perceptions and management of pain. Barriers and facilitators to chronic pain care were highlighted from their time in the military into their transition to civilian care. Participants described the impact of chronic pain on their overall well-being. Determining whether these findings are relevant to a larger population of Canadian veterans will be important for future research and knowledge translation to improve chronic pain care for Canadian veterans.

Contexte : On estime que 30 % des anciens combattants souffrent de douleur chronique, contre 20 % des Canadiens dans la population générale Les vétérans sont confrontés à des défis en matière de soins de santé lorsqu'ils quittent l'armée, ce qui augmente les difficultés pour obtenir des soins pour la douleur chronique.Objectifs : Nous avons exploré les expériences des vétérans des Forces armées canadiennes vivant avec une douleur chronique, leur transition des soins militaires aux soins civils, les obstacles et les facilitateurs perçus en matière de soins pour la douleur chronique, ainsi que les effets de cette douleur sur les différents aspects de leur bien-être.Méthodes : Nous avons réalisé une étude qualitative descriptive en utilisant des entretiens semi-structurés. Une approche à la fois déductive et inductive a été utilisée pour extraire des thèmes et des concepts à partir des transcriptions des entretiens.Résultats : Trente-cinq anciens combattants souffrant de douleur chronique ont participé à l'étude. Les participants ont déclaré que la douleur affectait leur vie de nombreuses façons, notamment en ayant un impact négatif sur leurs relations en limitant les activités de la vie quotidienne ainsi que les loisirs. Ils ont recensé des obstacles aux soins, notamment le manque d'accès à des médecins de famille ou aux services de soins de santé, la réticence à demander de l'aide, et les difficultés à obtenir une couverture pour les services d'Anciens Combattants Canada. Les facilitateurs comprennent le soutien d'autres anciens combattants et les ressources en ligne. La douleur chronique a eu des effets bidirectionnels sur différents aspects de leur bien-être.Conclusions : Les expériences de la douleur varient parmi les anciens combattants canadiens, et la culture militaire joue un rôle dans les perceptions et la prise en charge de la douleur. Les obstacles aux soins pour la douleur chronique, ainsi que les facilitateurs, ont été mis en évidence depuis leur temps dans l'armée jusqu'à leur transition vers les soins civils. Les participants ont décrit l'effet de la douleur chronique sur leur bien-être général. Il sera important de déterminer si ces résultats sont pertinents pour une population plus large d'anciens combattants canadiens dans le cadre de recherches futures et de l'application des connaissances, afin d'améliorer les soins pour la douleur chronique chez les anciens combattants canadiens.

The gene YEF3 function encoding translation elongation factor eEF3 is partially conserved across fungi.

Introduction: Translation is a fundamental process of life. In eukaryotes, the elongation step of translation is highly conserved and is driven by eukaryotic translation elongation factors (eEF)1A and eEF2. A significant variation of the elongation is the activity of eukaryotic elongation factor (eEF) 3 in Saccharomyces cerevisiae encoded by the gene yeast elongation factor (YEF3) with orthologs in all fungal species, a few algae, and some protists. In S. cerevisiae, YEF3 is an essential gene and eEF3 plays a critical role in translation elongation, as it promotes binding of the ternary complex acylated-Transfer RNA (tRNA)-eEF1A-Guanosine-5'-triphosphate (GTP) to the aminoacyl (A) site of the ribosome, the release of uncharged tRNAs after peptide translocation, and ribosome recycling. Even though YEF3 was discovered more than 40 years ago, eEF3 has been characterized almost exclusively in S. cerevisiae. Methods: We undertook an in vivo genetic approach to assess the functional conservation of eEF3 across phylogenetically distant fungal species. Results: We found that eEF3 from Zygosaccharomyces rouxii and Candida glabrata (both belonging to phylum Ascomycota), Ustilago maydis (phylum Basidiomycota), and Gonapodya prolifera (phylum Monoblepharomycota), but not Aspergillus nidulans (phylum Ascomycota), supported the growth of S. cerevisiae lacking the endogenous YEF3 gene. We also proved that eEF3 is an essential gene in the ascomycetes C. glabrata and A. nidulans. Discussion: Given that most existing knowledge on fungal translation has only been obtained from S. cerevisiae, our findings beyond this organism showed variability in the elongation process in Fungi. We also proved that eEF3 is essential in pathogenic fungi, opening the possibility of using eEF3 as a target to fight candidiasis.