Project description:Multiple approaches - including observational and experimental - are necessary to articulate powerful theories of learning. Our field's key questions, which rely on these varied methods, are still open. How do children perceive and produce language? What do they encounter in their linguistic input? What does the learner bring to the task of acquisition? Considerable progress has been made for the development of spoken English (especially by North American learners). Yet there is still a great deal to discover about how children in other populations proceed, especially populations in rural settings. To examine language learning in these populations, we need a multi-method approach. However, adapting and integrating methods, particularly experimental ones, to new settings can present immense challenges. In this paper, we discuss the opportunities and challenges facing researchers who aim to use a multimethodological approach in rural samples, and what the field of language acquisition can do to promote such work.

| S-EPMC10497711 | biostudies-literature

Challenges and Opportunities for Childhood Cancer Drug Development.

Project description:Cancer in children is rare with approximately 15,700 new cases diagnosed in the United States annually. Through use of multimodality therapy (surgery, radiation therapy, and aggressive chemotherapy), 70% of patients will be "cured" of their disease, and 5-year event-free survival exceeds 80%. However, for patients surviving their malignancy, therapy-related long-term adverse effects are severe, with an estimated 50% having chronic life-threatening toxicities related to therapy in their fourth or fifth decade of life. While overall intensive therapy with cytotoxic agents continues to reduce cancer-related mortality, new understanding of the molecular etiology of many childhood cancers offers an opportunity to redirect efforts to develop effective, less genotoxic therapeutic options, including agents that target oncogenic drivers directly, and the potential for use of agents that target the tumor microenvironment and immune-directed therapies. However, for many high-risk cancers, significant challenges remain.

| S-EPMC6768308 | biostudies-literature

Digital technologies as solutions to China's aging population: a systematic review of their opportunities and challenges in rural development.

Project description:IntroductionDifferences exist in the rate of aging between individuals residing in urban and rural areas in China, with rural areas experiencing a more pronounced impact. Smart aging represents a prevalent future trend in this regard, though its development will inevitably face challenges. However, studies focusing on rural areas are scarce. Future models of aging in less developed regions, including rural areas and townships, are expected to integrate and draw inspiration from the smart aging paradigm.MethodsWe present a systematic review of the current application of digital technologies in caring for older people in rural areas. We conducted extracted and screened 26 articles out of 823, sourced from five databases: Web of Science, IEEE Xplore, Engineering Village, PubMed/MEDLINE and CNKI.ResultsThe articles focus on digital technologies that cater to the daily life, medical care, spiritual comfort, and cultural entertainment needs of rural older people. In our review, we focused on four aspects of digital technology: mobile applications (apps), websites and platforms, mobile devices and terminals, and VR technologies or other unspecified technologies.DiscussionWe found that current digital technologies for smart aging have room for improvement in meeting the recreational and mental comfort needs of older adults. Digital technologies are predominantly applied to the smart community/rural and smart healthcare sectors, with limited applications in the smart home sector. Future studies should explore smart-home older adults care services to address digital cognitive barriers faced by older adults.

| S-EPMC11776298 | biostudies-literature

Development of Extracellular Vesicle Therapeutics: Challenges, Considerations, and Opportunities.

Project description:Extracellular vesicles (EVs) hold great promise as therapeutic modalities due to their endogenous characteristics, however, further bioengineering refinement is required to address clinical and commercial limitations. Clinical applications of EV-based therapeutics are being trialed in immunomodulation, tissue regeneration and recovery, and as delivery vectors for combination therapies. Native/biological EVs possess diverse endogenous properties that offer stability and facilitate crossing of biological barriers for delivery of molecular cargo to cells, acting as a form of intercellular communication to regulate function and phenotype. Moreover, EVs are important components of paracrine signaling in stem/progenitor cell-based therapies, are employed as standalone therapies, and can be used as a drug delivery system. Despite remarkable utility of native/biological EVs, they can be improved using bio/engineering approaches to further therapeutic potential. EVs can be engineered to harbor specific pharmaceutical content, enhance their stability, and modify surface epitopes for improved tropism and targeting to cells and tissues in vivo. Limitations currently challenging the full realization of their therapeutic utility include scalability and standardization of generation, molecular characterization for design and regulation, therapeutic potency assessment, and targeted delivery. The fields' utilization of advanced technologies (imaging, quantitative analyses, multi-omics, labeling/live-cell reporters), and utility of biocompatible natural sources for producing EVs (plants, bacteria, milk) will play an important role in overcoming these limitations. Advancements in EV engineering methodologies and design will facilitate the development of EV-based therapeutics, revolutionizing the current pharmaceutical landscape.

| S-EPMC8488228 | biostudies-literature

Opportunities and Challenges in Drug Development for Pediatric Cancers.

Project description:The use of targeted small-molecule therapeutics and immunotherapeutics has been limited to date in pediatric oncology. Recently, the number of pediatric approvals has risen, and regulatory initiatives in the United States and Europe have aimed to increase the study of novel anticancer therapies in children. Challenges of drug development in children include the rarity of individual cancer diagnoses and the high prevalence of difficult-to-drug targets, including transcription factors and epigenetic regulators. Ongoing pediatric adaptation of biomarker-driven trial designs and further exploration of agents targeting non-kinase drivers constitute high-priority objectives for future pediatric oncology drug development. SIGNIFICANCE: Increasing attention to drug development for children with cancer by regulators and pharmaceutical companies holds the promise of accelerating the availability of new therapies for children with cancer, potentially improving survival and decreasing the acute and chronic toxicities of therapy. However, unique approaches are necessary to study novel therapies in children that take into account low patient numbers, the pediatric cancer genomic landscape and tumor microenvironment, and the need for pediatric formulations. It is also critical to evaluate the potential for unique toxicities in growing hosts without affecting the pace of discovery for children with these life-threatening diseases.

| S-EPMC7933059 | biostudies-literature

Minireview: Challenges and opportunities in development of PPAR agonists.

Project description:The clinical impact of the fibrate and thiazolidinedione drugs on dyslipidemia and diabetes is driven mainly through activation of two transcription factors, peroxisome proliferator-activated receptors (PPAR)-α and PPAR-γ. However, substantial differences exist in the therapeutic and side-effect profiles of specific drugs. This has been attributed primarily to the complexity of drug-target complexes that involve many coregulatory proteins in the context of specific target gene promoters. Recent data have revealed that some PPAR ligands interact with other non-PPAR targets. Here we review concepts used to develop new agents that preferentially modulate transcriptional complex assembly, target more than one PPAR receptor simultaneously, or act as partial agonists. We highlight newly described on-target mechanisms of PPAR regulation including phosphorylation and nongenomic regulation. We briefly describe the recently discovered non-PPAR protein targets of thiazolidinediones, mitoNEET, and mTOT. Finally, we summarize the contributions of on- and off-target actions to select therapeutic and side effects of PPAR ligands including insulin sensitivity, cardiovascular actions, inflammation, and carcinogenicity.

| S-EPMC5414793 | biostudies-literature

Metallodrugs are unique: opportunities and challenges of discovery and development.

Project description:Metals play vital roles in nutrients and medicines and provide chemical functionalities that are not accessible to purely organic compounds. At least 10 metals are essential for human life and about 46 other non-essential metals (including radionuclides) are also used in drug therapies and diagnostic agents. These include platinum drugs (in 50% of cancer chemotherapies), lithium (bipolar disorders), silver (antimicrobials), and bismuth (broad-spectrum antibiotics). While the quest for novel and better drugs is now as urgent as ever, drug discovery and development pipelines established for organic drugs and based on target identification and high-throughput screening of compound libraries are less effective when applied to metallodrugs. Metallodrugs are often prodrugs which undergo activation by ligand substitution or redox reactions, and are multi-targeting, all of which need to be considered when establishing structure-activity relationships. We focus on early-stage in vitro drug discovery, highlighting the challenges of evaluating anticancer, antimicrobial and antiviral metallo-pharmacophores in cultured cells, and identifying their targets. We highlight advances in the application of metal-specific techniques that can assist the preclinical development, including synchrotron X-ray spectro(micro)scopy, luminescence, and mass spectrometry-based methods, combined with proteomic and genomic (metallomic) approaches. A deeper understanding of the behavior of metals and metallodrugs in biological systems is not only key to the design of novel agents with unique mechanisms of action, but also to new understanding of clinically-established drugs.

| S-EPMC8163330 | biostudies-literature

Opportunities and challenges in the development of exoskeletons for locomotor assistance.

Project description:Exoskeletons can augment the performance of unimpaired users and restore movement in individuals with gait impairments. Knowledge of how users interact with wearable devices and of the physiology of locomotion have informed the design of rigid and soft exoskeletons that can specifically target a single joint or a single activity. In this Review, we highlight the main advances of the past two decades in exoskeleton technology and in the development of lower-extremity exoskeletons for locomotor assistance, discuss research needs for such wearable robots and the clinical requirements for exoskeleton-assisted gait rehabilitation, and outline the main clinical challenges and opportunities for exoskeleton technology.

| S-EPMC11536595 | biostudies-literature

Model Informed Drug Development and Regulation in China: Challenges and Opportunities.

Project description: Not available

| S-EPMC6389345 | biostudies-literature