[Key considerations in the process of assent in children and adolescents: an integrative review]. / Consideraciones claves en el proceso de asentimiento en niños, niñas y adolescentes: revisión integrativa.

The participation of children and adolescents in research requires bioethical measures to safeguard their autonomy and well-being through the application of the informed consent process. OBJECTIVE: To critically analyze the factors involved in the process of assent/consent in children and adolescents in research. METHODOLOGY: Integrative review of scientific evidence carried out between April and June 2023, from manuscripts published between 2014 and 2023 in Web of Science, PubMed, CUIDEN, and CINAHL databases, using the descriptors Process Assessment OR Assent AND Informed Consent AND Bioethics AND Minors OR Child OR Children AND adolescent OR teenage AND Pediatrics AND Research. Twenty primary articles were found, and the results were subjected to content analysis. RESULT: Three categories were identified: shared consent/assent; child-specific factors for giving assent (age of the child to give assent and autonomy of the child to give assent), and key aspects of the assent process (assent form format; assent form content, and context for applying the assent process). CONCLUSIONS: The assent process is a key tool for legal and ethical compliance with the rights of children and adolescents in clinical trial participation. In addition to favoring participation in informed decision-making together with the parents, it is also an instance where the participant's competencies, capacity for understanding, and autonomy are valued.

Coproducing health research with Indigenous peoples.

The coproduction of health research represents an important advance in the realm of participatory methodologies, which have evolved over the past five decades. This transition to a collaborative approach emphasizes shared control between academic researchers and their partners, fostering a more balanced influence on the research process. This shift not only enhances the quality of the research and the evidence generated, but also increases the likelihood of successful implementation. For Indigenous peoples, coproduced research represents a critical development, enabling a shift from being mere 'subjects' of research to being active controllers of the process-including addressing the extractive and oppressive practices of the past. In this Review, we explore how research coproduction with Indigenous peoples is evolving. An 'Indigenous turn' embraces the concept of shared control while also considering the principles of reciprocity, the incommensurability of Western and Indigenous knowledge systems, divergent ethical standards, strategic and political differences, and the broader impact of processes and outcomes. To illustrate these ideas, we present examples involving New Zealand's Maori communities and offer recommendations for further progress.

Engineered organoids for biomedical applications.

As miniaturized and simplified stem cell-derived 3D organ-like structures, organoids are rapidly emerging as powerful tools for biomedical applications. With their potential for personalized therapeutic interventions and high-throughput drug screening, organoids have gained significant attention recently. In this review, we discuss the latest developments in engineering organoids and using materials engineering, biochemical modifications, and advanced manufacturing technologies to improve organoid culture and replicate vital anatomical structures and functions of human tissues. We then explore the diverse biomedical applications of organoids, including drug development and disease modeling, and highlight the tools and analytical techniques used to investigate organoids and their microenvironments. We also examine the latest clinical trials and patents related to organoids that show promise for future clinical translation. Finally, we discuss the challenges and future perspectives of using organoids to advance biomedical research and potentially transform personalized medicine.

Building blocks for better biorepositories in Africa.

BACKGROUND: Biorepositories archive and distribute well-characterized biospecimens for research to support the development of medical diagnostics and therapeutics. Knowledge of biobanking and associated practices is incomplete in low- and middle-income countries where disease burden is disproportionately high. In 2011, the African Society of Human Genetics (AfSHG), the National Institutes of Health (NIH), and the Wellcome Trust founded the Human Heredity and Health in Africa (H3Africa) consortium to promote genomic research in Africa and established a network of three biorepositories regionally located in East, West, and Southern Africa to support biomedical research. This manuscript describes the processes established by H3Africa biorepositories to prepare research sites to collect high-quality biospecimens for deposit at H3Africa biorepositories. METHODS: The biorepositories harmonized practices between the biorepositories and the research sites. The biorepositories developed guidelines to establish best practices and define biospecimen requirements; standard operating procedures (SOPs) for common processes such as biospecimen collection, processing, storage, transportation, and documentation as references; requirements for minimal associated datasets and formats; and a template material transfer agreements (MTA) to govern biospecimen exchange. The biorepositories also trained and mentored collection sites in relevant biobanking processes and procedures and verified biospecimen deposit processes. Throughout these procedures, the biorepositories followed ethical and legal requirements. RESULTS: The 20 research projects deposited 107,982 biospecimens (76% DNA, 81,067), in accordance with the ethical and legal requirements and established best practices. The biorepositories developed and customized resources and human capacity building to support the projects. [The biorepositories developed 34 guidelines, SOPs, and documents; trained 176 clinicians and scientists in over 30 topics; sensitized ethical bodies; established MTAs and reviewed consent forms for all projects; attained import permits; and evaluated pilot exercises and provided feedback. CONCLUSIONS: Biobanking in low- and middle-income countries by local skilled staff is critical to advance biobanking and genomic research and requires human capacity and resources for global partnerships. Biorepositories can help build human capacity and resources to support biobanking by partnering with researchers. Partnerships can be structured and customized to incorporate document development, ethics, training, mentorship, and pilots to prepare sites to collect, process, store, and transport biospecimens of high quality for future research.

Utilization of anonymization techniques to create an external control arm for clinical trial data.

BACKGROUND: Subject-level real-world data (RWD) collected during daily healthcare practices are increasingly used in medical research to assess questions that cannot be addressed in the context of a randomized controlled trial (RCT). A novel application of RWD arises from the need to create external control arms (ECAs) for single-arm RCTs. In the analysis of ECAs against RCT data, there is an evident need to manage and analyze RCT data and RWD in the same technical environment. In the Nordic countries, legal requirements may require that the original subject-level data be anonymized, i.e., modified so that the risk to identify any individual is minimal. The aim of this study was to conduct initial exploration on how well pseudonymized and anonymized RWD perform in the creation of an ECA for an RCT. METHODS: This was a hybrid observational cohort study using clinical data from the control arm of the completed randomized phase II clinical trial (PACIFIC-AF) and RWD cohort from Finnish healthcare data sources. The initial pseudonymized RWD were anonymized within the (k, ε)-anonymity framework (a model for protecting individuals against identification). Propensity score matching and weighting methods were applied to the anonymized and pseudonymized RWD, to balance potential confounders against the RCT data. Descriptive statistics for the potential confounders and overall survival analyses were conducted prior to and after matching and weighting, using both the pseudonymized and anonymized RWD sets. RESULTS: Anonymization affected the baseline characteristics of potential confounders only marginally. The greatest difference was in the prevalence of chronic obstructive pulmonary disease (4.6% vs. 5.4% in the pseudonymized compared to the anonymized data, respectively). Moreover, the overall survival changed in anonymization by only 8% (95% CI 4-22%). Both the pseudonymized and anonymized RWD were able to produce matched ECAs for the RCT data. Anonymization after matching impacted overall survival analysis by 22% (95% CI -21-87%). CONCLUSIONS: Anonymization may be a viable technique for cases where flexible data transfer and sharing are required. As anonymization necessarily affects some aspects of the original data, further research and careful consideration of anonymization strategies are needed.

Guías para la elaboración de manuscritos y unas pinceladas de lectura crítica / Reporting guidelines and a touch of critical appraisal

El proceso de investigación biomédica debe seguir unos criterios de calidad en su diseño y elaboración que garanticen que los resultados son creíbles y fiables. Una vez finalizado, llega el momento de escribir un artículo para su publicación. Este debe presentar con suficiente detalle, y de forma clara y transparente, toda la información del trabajo de investigación realizado. De esta forma, los lectores, tras una lectura crítica de lo publicado, podrán juzgar la validez y la relevancia del estudio, y si lo consideran, utilizar los hallazgos. Con el objetivo de mejorar la descripción del proceso de investigación para su publicación, se han desarrollado una serie de guías que, de forma sencilla y estructurada, orientan a los autores a la hora de elaborar un manuscrito. Se presentan en forma de lista, diagrama de flujo, o texto estructurado, y son una ayuda inestimable a la hora de escribir un artículo. Este artículo presenta las guías de elaboración de manuscritos de los diseños más habituales, con sus listas de verificación.(AU)

The biomedical research process must follow certain quality criteria in its design and development to ensure that the results are credible and reliable. Once completed, the time comes to write an article for publication. The article must present in sufficient detail, and in a clear and transparent manner, all the information on the research work that has been carried out. In this way, readers, after a critical reading of the published content, will be able to judge the validity and relevance of the study and, if they so wish, make use of the findings. In order to improve the description of the research process for publication, a series of guidelines have been developed which, in a simple and structured way, guide authors in the preparation of a manuscript. They are presented in the form of a list, flowchart, or structured text, and are an invaluable aid when writing an article. This article presents the reporting guidelines for the most common designs along with the corresponding checklists.(AU)

Navigating data governance associated with real-world data for public benefit: an overview in the UK and future considerations.

Real-world data encompass data primarily captured for the provision or operation of services, for example, electronic health records for direct care purposes, but which may have secondary uses for informing research or commissioning. Public benefit is potentially forfeited by the underutilisation of real-world data for secondary uses, in part due to risk aversion when faced with the prospect of navigating necessary and important data governance processes. Such processes can be perceived as complex, daunting, time-consuming and exposing organisations to risk. By providing an overview description and discussion around the role of six key legal and information governance frameworks and their role regarding responsible data access, linkage and sharing, our intention is to make data governance a less daunting prospect and reduce the perception that it is a barrier to secondary uses, thus enabling public benefit.

Estudios epidemiológicos o cómo tenemos que diseñar nuestra investigación (primera parte) / Epidemiological studies or how should we design our research? (part one)

El conocimiento en metodología es imprescindible para poner en marcha nuestros proyectos de investigación y nuestros diseños epidemiológicos. Plantear adecuadamente un diseño nos permitirá comunicar debidamente los resultados de nuestra experiencia clínica. Existen diferentes tipos de diseño en función de múltiples factores, como la participación activa del investigador, la aleatorización de los pacientes o la formación del grupo control. Conocerlos es fundamental para saber cuál es el más apropiado para comenzar nuestra andadura como investigadores. En este trabajo mostramos las características y la terminología con las que nos referimos a los diferentes diseños epidemiológicos y expondremos algunos de estos diseños, que terminaremos de ver en próximos artículos.(AU)

Methodological knowledge is essential to implement our research projects and epidemiological designs. adequatedesign will allow us to adequately communicate the results of our clinical experience.there are different types of design depending on multiple factors such as the active participation of the investigator,the randomization of patients or the composition of the control group. it is essential to be familiar with them inorder to know which is the most appropriate to start our journey as researchers.in this paper we show the characteristics and terminology with which we refer to the different epidemiologicaldesigns and we will present some of these designs, which we will finish in future papers.(AU)

Metal-organic frameworks (MOFs) as effectual diagnostic and therapeutic tools for cancer.

Metal-organic frameworks (MOFs) are a class of multifunctional organometallic compounds that include metal ions combined with assorted organic linkers. Recently, these compounds have received widespread attention in medicine, due to their exceptional qualities, including a wide surface area, high porosity, outstanding biocompatibility, non-toxicity, etc. Such characteristic qualities make MOFs superb candidates for biosensing, molecular imaging, drug delivery, and enhanced cancer therapies. This review illustrates the key attributes of MOFs and their importance in cancer research. The structural and synthetic aspects of MOFs are briefly discussed with primary emphasis on diagnostic and therapeutic features, as well as their performance and significance in modern therapeutic methods and synergistic theranostic strategies including biocompatibility. This review offers cumulative scrutiny of the widespread appeal of MOFs in modern-day oncological research, which may stimulate further explorations.

Lipidic lyotropic liquid crystals: Insights on biomedical applications.

Liquid crystals (LCs) possess unique physicochemical properties, translatable into a wide range of applications. To date, lipidic lyotropic LCs (LLCs) have been extensively explored in drug delivery and imaging owing to the capability to encapsulate and release payloads with different characteristics. The current landscape of lipidic LLCs in biomedical applications is provided in this review. Initially, the main properties, types, methods of fabrication and applications of LCs are showcased. Then, a comprehensive discussion of the main biomedical applications of lipidic LLCs accordingly to the application (drug and biomacromolecule delivery, tissue engineering and molecular imaging) and route of administration is examined. Further discussion of the main limitations and perspectives of lipidic LLCs in biomedical applications are also provided. STATEMENT OF SIGNIFICANCE: Liquid crystals (LCs) are those systems between a solid and liquid state that possess unique morphological and physicochemical properties, translatable into a wide range of biomedical applications. A short description of the properties of LCs, their types and manufacturing procedures is given to serve as a background to the topic. Then, the latest and most innovative research in the field of biomedicine is examined, specifically the areas of drug and biomacromolecule delivery, tissue engineering and molecular imaging. Finally, prospects of LCs in biomedicine are discussed to show future trends and perspectives that might be utilized. This article is an ampliation, improvement and actualization of our previous short forum article "Bringing lipidic lyotropic liquid crystal technology into biomedicine" published in TIPS.

Health registries as research tools: a review of methodological key issues.

Health registries provide opportunities for conducting large-scale, population-based studies, but attention must be devoted to their specific limitations. Herein, we describe potential limitations that may affect the validity of registry-based research. Our review includes descriptions of 1) populations, 2) variables, 3) medical coding systems for medical information and 4) selected key methodological challenges. Knowledge of such factors and epidemiological study designs in general is likely to increase the quality of registry-based research and reduce potential biases.

An evaluation of programs to support new investigators at the National Institute of Allergy and Infectious Diseases: Striking a balance with funding for established investigators.

As the largest funder of basic biomedical research in the US, the National Institutes of Health (NIH) has an interest in maintaining a sustainable, productive workforce of investigators. Over the years, NIH has implemented several programs to attract early-stage investigators and other applicants without prior NIH support. The latest of these is the Next Generation Researchers Initiative. These programs have been shown to be successful in meeting NIH-wide goals but their success for any particular NIH institute or center (IC), and in any particular year, is determined by a variety of factors, some extrinsic to an IC's funding decision process. Each IC must balance support for new investigators with funding for productive ongoing programs of research. We examine historical trends in support of new investigators at the National Institute of Allergy and Infectious Diseases (NIAID) over a 22-year period, as well as trends in some major extrinsic influences on that support. The results indicate that NIH's new investigator programs have succeeded in maintaining a balance between the support for new NIAID investigators while also continuing to support an expanded pool of established investigators. The programs have been particularly effective in providing support to early-stage investigators.

How do scientists model humanness? A qualitative study of human organoids in biomedical research.

We investigate how changes in biotechnology are transforming the pursuit of human-specific models of disease and development. Our case study focuses on scientists who make human organoids. Organoids are stem cell-based three-dimensional multicellular living systems, made in labs, that mimic the function of human organs. Organoids create new opportunities for human health research, but we know little about how researchers understand the relationship between these model systems and the humans they are meant to represent. By analysing 25 interviews, complemented by observation and documentary research conducted in 2020-2022, we identify and discuss four themes that characterize how researcher's model humanness in organoids. For scientists, organoids are powerful tools to approximate the biology of human beings because they represent the closest thing to undertaking experiments on living humans, not previously possible. As laboratory tools, human organoids may replace the need for experimentation on animals, potentially contributing to the 3Rs of animal research (replacement, reduction, and refinement). Humanness is partly operationalized by modelling different human characteristics within organoids, such as male and female, different disease states, age, and other attributes. We find that human organoids are opening up previously closed spaces of experimentation and modelling in biomedicine. We argue that the humanness of organoid model systems are not a given but are enacted with and through a variety of scientific practices. These practices require critical attention from social scientists as the enactments of humanness being modelled in organoids have the potential to shape what and who counts as human in biomedical research.

Advancing research on early autism through an integrated risk and resilience perspective.

To date, a deficit-oriented approach dominates autism spectrum disorder (ASD) research, including studies of infant siblings of children with ASD at high risk (HR) for the disabilities associated with this disorder. Despite scientific advances regarding early ASD-related risk, there remains little systematic investigation of positive development, limiting the scope of research and quite possibly a deeper understanding of pathways toward and away from ASD-related impairments. In this paper, we argue that integrating a resilience framework into early ASD research has the potential to enhance knowledge on prodromal course, phenotypic heterogeneity, and developmental processes of risk and adaptation. We delineate a developmental systems resilience framework with particular reference to HR infants. To illustrate the utility of a resilience perspective, we consider the "female protective effect" and other evidence of adaptation in the face of ASD-related risk. We suggest that a resilience framework invites focal questions about the nature, timing, levels, interactions, and mechanisms by which positive adaptation occurs in relation to risk and developmental pathways toward and away from ASD-related difficulties. We conclude with recommendations for future research, including more focus on adaptive development and multisystem processes, pathways away from disorder, and reconsideration of extant evidence within an integrated risk-and-resilience framework.

How to Use Microhistory Methodology in Mental Health Research.

Incorporating anthropological principles, microhistory is a research methodology useful for exploring the interplay between ordinary people and social abstractions such as, the market, social systems, and governments. In this paper, the background and characteristics of microhistory are described, and a novel six-stage approach for conducting microhistories in mental healthcare is introduced. Each stage of the process is illustrated using sections from a microhistory focussed on the earliest recorded case comparison between British colonial mental healthcare and Aboriginal Australian traditional healing. Microhistory provides a way to uncover new insights about past mental healthcare, which may contribute to re-conceptualisations of modern-day beliefs and practices.