OVERCOMING THE CHALLENGES OF TECHNOLOGY IN GERONTOLOGICAL RESEARCH
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ABSTRACT:
SUBMITTER: Lindsey J
PROVIDER: S-EPMC6845002 | biostudies-literature | 2019 Nov
REPOSITORIES: biostudies-literature
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Project description:Triple-negative breast cancer (TNBC) is a pathological term used to identify invasive breast cancers that lack expression of estrogen and progesterone receptors and do not have pathologic overexpression of the HER2 receptor or harbor ERBB2 gene amplification. TNBC includes a collection of multiple distinct disease entities based upon genomic, transcriptomic and phenotypic characterization. Despite improved clinical outcomes with the development of novel therapeutics, TNBC still yields the worst prognosis among all clinical subtypes of breast cancer. We will systematically review evidence of the genomic evolution of TNBC, as well as potential mechanisms of disease progression and treatment resistance, defined in part by advances in next-generation DNA sequencing technology (including single cell sequencing), providing a new perspective on treatment strategies, and promise to reveal new potential therapeutic targets. Moreover, we review novel therapies aimed at homologous recombination deficiency, PI3 kinase/AKT/PTEN pathway activation, androgen receptor blockade, immune checkpoint inhibition, as well as antibody-drug conjugates engaging novel cell surface targets, including recent progress in pre-clinical and clinical studies which further validate the role of targeted therapies in TNBC. Despite major advances in treatment for TNBC, including FDA approval of 2 PARP inhibitors for metastatic TNBC, the crossing of the superiority boundary in a phase 3, placebo-controlled study of adjuvant olaparib in early-stage patients with germline BRCA-mutated high-risk HER2-negative early breast cancer, the FDA approval of 2 PD-(L)1 checkpoint antibodies for metastatic TNBC, and the FDA approval of the first antibody drug conjugate for TNBC, significant challenges remain. For example, despite the dawn of immunotherapy in metastatic TNBC, durable responses are limited to a small subset of patients, definitive biomarkers for patient selection are lacking, and the Oncology Drug Advisory Committee to the FDA has recently voted against approval of an anti-PD-1 checkpoint antibody high risk early-stage TNBC in the neoadjuvant setting. Also, despite early positive randomized phase 2 studies of AKT inhibition in metastatic TNBC, a recent phase 3 registration trial failed to validate earlier phase 2 data. Finally, we note that level one evidence for clinical efficacy of androgen receptor blockade in TNBC is still lacking. To meet these and other challenges, we will catalogue the ongoing exponential increase in interest in basic, translational, and clinical research to develop new treatment paradigms for TNBC.
| S-EPMC8654168 | biostudies-literature
Project description: Not available
| S-EPMC4597938 | biostudies-literature
Project description:ObjectivesAfter a long history of neglect, diversity among older people and increasing heterogeneity with age are now familiar ideas in gerontological discourse. We take up the question of whether this increased attention is translating into the domain of empirical research. We replicate Nelson and Dannefer's (1992) review of the treatment of age-based variability in gerontological research, the most recent known assessment of the issue.MethodA sample of empirical studies was drawn from six gerontological journals to determine (a) whether measures of within-age variability were reported and/or discussed and (b) if reported, the observed age-based pattern of variability in the outcome(s).ResultsThe majority of studies neither reported nor discussed age-based variability. Among those that did report, the great majority indicated either stability or increasing variability with age. Observed patterns varied by outcome type. Although a majority of analyses of psychological and social outcomes suggested that variability was stable across age, half of the analyses of biological/health outcomes indicated increasing variability. Overall, very few (3%) of studies suggested decreasing variability.DiscussionConsistent with earlier reports of studies, researchers continue to focus on average differences between age groups, yet key issues in social gerontology require attention to intra-age variability.
| S-EPMC6283321 | biostudies-literature
Project description:Oncolytic virotherapy (OVT) is a promising approach in which WT or engineered viruses selectively replicate and destroy tumor cells while sparing normal ones. In the last two decades, different oncolytic viruses (OVs) have been modified and tested in a number of preclinical studies, some of which have led to clinical trials in cancer patients. These clinical trials have revealed several critical limitations with regard to viral delivery, spread, resistance, and antiviral immunity. Here, we focus on promising research strategies that have been developed to overcome the aforementioned obstacles. Such strategies include engineering OVs to target a broad spectrum of tumor cells while evading the immune system, developing unique delivery mechanisms, combining other immunotherapeutic agents with OVT, and using clinically translatable mouse tumor models to potentially translate OVT more readily into clinical settings.
| S-EPMC6436848 | biostudies-literature
Project description:Major technical challenges often prevent developers from producing new point-of-care technologies that deliver the required clinical performance in the intended settings of use. But even when devices meet clinical requirements, they can fail to be adopted and successfully implemented. Adoption barriers occur when decision makers do not understand the "value proposition" of new technologies. Current discussions of value in the context of point-of-care testing focus predominantly on the intended use and performance of the device from the manufacturer's point-of-view. However, the perspective of potential adopters in determining whether new devices provide value is also important, as is the opinion of all stakeholders who will be impacted. Incorporating value concepts into decisions made across the full development-to-adoption continuum can increase the likelihood that point-of-care testing will have the desired impact on health care delivery and patient outcomes. This article discusses how various approaches to technology development impact adoption and compares the characteristics of these approaches to emerging value concepts. It also provides an overview of value initiatives and tools that are being developed to support the evaluation of value propositions. These are presented for a range of technology adoption decision contexts, with particular applicability to point-of-care testing. Expanding the focus of research to address gaps in both the creation and evaluation of value propositions is imperative in order for value concepts to positively influence the adoption of point-of-care testing.
| S-EPMC7751984 | biostudies-literature
Project description:BACKGROUND:Blockchain offers a promising new distributed technology to address the challenges of data standardization, system interoperability, security, privacy, and accessibility of medical records. OBJECTIVE:The purpose of this review is to assess the research on the use of blockchain technology for patient care and the associated challenges and to provide a research agenda for future research. METHODS:This review followed the Preferred Reporting Items for Systematic Reviews and Meta-Analysis guidelines. We queried the Cumulative Index of Nursing and Allied Health Literature (CINAHL), PubMed, Excerpta Medica dataBASE (EMBASE), and Web of Science databases for peer-reviewed research articles published up to December 2019 that examined the implementation of blockchain technology in health care settings. We identified 800 articles from which we selected 70 empirical research articles for a detailed review. RESULTS:Blockchain-based patient care applications include medical information systems, personal health records, mobile health and telemedicine, data preservation systems and social networks, health information exchanges and remote monitoring systems, and medical research systems. These blockchain-based health care applications may improve patient engagement and empowerment, improve health care provider access to information, and enhance the use of health care information for medical research. CONCLUSIONS:Blockchain health information technology (HIT) provides benefits such as ensuring data privacy and security of health data, facilitating interoperability of heterogeneous HIT systems, and improving the quality of health care outcomes. However, barriers to using blockchain technology to build HIT include security and privacy vulnerabilities, user resistance, high computing power requirements and implementation costs, inefficient consensus algorithms, and challenges of integrating blockchain with existing HIT. With 51% of the research focused on medical information systems such as electronic health record and electronic medical record, and 53% of the research focused on data security and privacy issues, this review shows that HIT research is primarily focused on the use of blockchain technologies to address the current challenges HIT faces. Although Blockchain presents significant potential for disrupting health care, most ideas are in their infancy.
| S-EPMC7399962 | biostudies-literature
Project description:ObjectiveThere is evidence linking the built environment (BE) with physical activity (PA), but few studies have been conducted in Latin America (LA). State-of-the-art methods and protocols have been designed in and applied in high-income countries (HIC). In this paper, we identify key challenges and potential solutions to conducting high-quality PA and BE research in LA.MethodsThe experience of implementing the IPEN data collection protocol (IPEN: International Physical Activity Environment Network) in Curitiba, Brazil; Bogotá, Colombia; and Cuernavaca, Mexico (2010-2011); is described to identify challenges for conducting PA and BE research in LA.ResultsFive challenges were identified: lack of academic capacity (implemented solutions (IS): building a strong international collaborative network); limited data availability, access and quality (IS: partnering with influential local institutions, and crafting creative solutions to use the best-available data); socio-political, socio-cultural and socio-economic context (IS: in-person recruitment and data collection, alternative incentives); safety (IS: strict rules for data collection procedures, and specific measures to increase trust); and appropriateness of instruments and measures (IS: survey adaptation, use of standardized additional survey components, and employing a context-based approach to understanding the relationship between PA and the BE). Advantages of conducting PA and BE research in LA were also identified.ConclusionsConducting high-quality PA and BE research in LA is challenging but feasible. Networks of institutions and researchers from both HIC and LMIC play a key role. The lessons learned from the IPEN LA study may be applicable to other LMIC.
| S-EPMC4268364 | biostudies-literature
Project description:Withstanding 3.5 billion years of genetic drift, the canonical genetic code remains such a fundamental foundation for the complexity of life that it is highly conserved across all three phylogenetic domains. Genome engineering technologies are now making it possible to rationally change the genetic code, offering resistance to viruses, genetic isolation from horizontal gene transfer, and prevention of environmental escape by genetically modified organisms. We discuss the biochemical, genetic, and technological challenges that must be overcome in order to engineer the genetic code.
| S-EPMC4779434 | biostudies-literature
Project description:PurposePalliative care is increasingly viewed as a necessary component of cancer care, especially for patients with advanced disease. Rigorous clinical trials are thus needed to build the palliative care evidence base, but clinical research-especially participant recruitment-is difficult. Major barriers include (1) patient factors, (2) "gatekeeping," and (3) ethical concerns. Here we discuss an approach to overcoming these barriers, using the Palliative Care Trial (PCT) as a case study.Patients and methodsThe PCT was a 2 × 2 × 2 factorial randomized controlled trial (RCT) of different service delivery models to improve pain control in the palliative setting. It used a recruitment protocol that fused evidence-based strategies with principles of "social marketing," an approach involving the systematic application of marketing techniques. Main components included (1) an inclusive triage algorithm, (2) information booklets targeting particular stakeholders, (3) a specialized recruitment nurse, and (4) standardization of wording across all study communications.ResultsFrom an eligible pool of 607 patients, the PCT enrolled 461 patients over 26 months. Twenty percent of patients referred to the palliative care service were enrolled (76% of those eligible after screening). Several common barriers were minimized; among those who declined participation, family disinterest was uncommon (5%), as was the perception of burden imposed (4%).ConclusionChallenges to clinical trial recruitment in palliative care are significant but not insurmountable. A carefully crafted recruitment and retention protocol can be effective. Our experience with designing and deploying a social-marketing-based protocol shows the benefits of such an approach.
| S-EPMC3825289 | biostudies-literature
Project description:Glycoproteomics has emerged as a prime area of interest within the field of proteomics because glycoproteins have been shown to function as biomarkers for disease and as promising therapeutic targets. A significant challenge in the study of glycoproteins is the fact that they are expressed in relatively low abundance in cells. In response, various enrichment methods have been developed to improve the detection of glycoproteins. One such method involves their capture via oxidation of their glycan chains and covalent attachment with hydrazide resins which, when catalyzed by PNGase F, release N-linked glycans and convert the glycosite Asn to Asp; this conversion is identifiable with LC/ESI-MS/MS as a corresponding increase of 0.984 Da in molecular weight. The present study builds on this body of work, providing evidence of three additional strategies that improve glycoprotein identification: (1) use of a high resolution mass spectrometer-the Q Exactive MS-which delivers 2-3 times more glycoprotein identifications than a low resolution MS; (2) optimization of instrument settings and database search parameters to reduce misidentification of N-linked glycopeptides to ~1 percent; and (3) labeling glycopeptides with (18)O during PNGase F treatment to locate N-linked glycosites within peptides containing multiple N-linked sequons.
| S-EPMC4002168 | biostudies-literature