Why regenerative stem cell medicine progresses slower than expected

Stem cell research has been acclaimed to revolutionize the future of medicine, and to offer new treatments for previously incurable diseases. Despite years of research, however, the therapeutic potential of stem cell research has not yet been fully realized. By June 2014, the US Food and Drug Administration had approved only five stem cell-based medicinal products, all of which cord blood derived hematopoietic stem cell products for the cure of blood and immunological diseases. Anticipated treatments for cancer, neurodegenerative disorders, gastroenterological, myocardial, and other diseases are still far from routine applications. What are the reasons for the slow progress in the stem cell field, and the mismatch between public expectations and actual achievements

Smart Cupboard for Assessing Memory in Home Environment

Sensor systems for the Internet of Things (IoT) make it possible to continuously monitor people, gathering information without any extra effort from them. Thus, the IoT can be very helpful in the context of early disease detection, which can improve peoples'' quality of life by applying the right treatment and measures at an early stage. This paper presents a new use of IoT sensor systemswe present a novel three-door smart cupboard that can measure the memory of a user, aiming at detecting potential memory losses. The smart cupboard has three sensors connected to a Raspberry Pi, whose aim is to detect which doors are opened. Inside of the Raspberry Pi, a Python script detects the openings of the doors, and classifies the events between attempts of finding something without success and the events of actually finding it, in order to measure the user''s memory concerning the objects'' locations (among the three compartments of the smart cupboard). The smart cupboard was assessed with 23 different users in a controlled environment. This smart cupboard was powered by an external battery. The memory assessments of the smart cupboard were compared with a validated test of memory assessment about face-name associations and a self-reported test about self-perceived memory. We found a significant correlation between the smart cupboard results and both memory measurement methods. Thus, we conclude that the proposed novel smart cupboard successfully measured memory

Collaboration of Smart IoT Devices Exemplified With Smart Cupboards

[EN] The variety of smart things connected to Internet hampers the possibility of having a standalone solution for service-centric provisioning in the Internet of Things (IoT). The different features of smart objects in processing capabilities, memory, and size make it difficult for final users to learn the installation and usage of all these devices in collaboration with other IoT objects, hindering the user experience. In this context, we propose a collaboration mechanism for IoT devices based on the multi-agent systems with mobile agents. This paper illustrates the current approach with smart cupboards for potentially tracking memory losses. The user study revealed that users found working products of this approach usable, easy-to-learn and useful, and they agreed that the current approach could provide a high quality of experience not only in the specific case of service-centric IoT devices for tracking memory losses but also in other domains. The learning capability by means of this approach was showed with significant reductions of reaction times and number of errors over the first and second tests with the current approach. System response timesThis work was supported in part by the Dpto. de Innovacion, Investigacion y Universidad del Gobierno de Aragon through the program FEDER Aragon 2014-2020 Construyendo Europa desde Aragon under Grant T49_17R, in part by the University of Zaragoza and the Foundation Ibercaja through the Research Project Construccion de un framework para agilizar el desarrollo de aplicaciones moviles en el ambito de la salud under Grant JIUZ-2017-TEC-03, in part by the Estancias de movilidad en el extranjero Jose Castillejo para jovenes doctores Program, Spanish Ministry of Education, Culture and Sport, under Grant CAS17/00005, in part by the Universidad de Zaragoza, Fundacion Bancaria Ibercaja and Fundacion CAI, Programa Ibercaja-CAI de Estancias de Investigacion, under Grant IT24/16 and Grant IT1/18, in part by the Research Project Desarrollo Colaborativo de Soluciones AAL, Spanish Ministry of Economy and Competitiveness, under Grant TIN2014-57028-R, in part by the Organismo Autonomo Programas Educativos Europeos under Grant 2013-1-CZ1-GRU06-14277, and in part by the Ministerio de Economia y Competitividad through the Programa Estatal de Fomento de la Investigacion Cientifica y Tecnica de Excelencia, Subprograma Estatal de Generacion de Conocimiento, under Grant TIN2017-84802-C2-1-P.García-Magariño, I.; González-Landero, F.; Amariglio, R.; Lloret, J. (2019). Collaboration of Smart IoT Devices Exemplified With Smart Cupboards. IEEE Access. 7:9881-9892. https://doi.org/10.1109/ACCESS.2018.2890393S98819892

Head-mounted display-based application for cognitive training

Virtual Reality (VR) has had significant advances in rehabilitation, due to the gamification of cognitive activities that facilitate treatment. On the other hand, Immersive Virtual Reality (IVR) produces outstanding results due to the interactive features with the user. This work introduces a VR application for memory rehabilitation by walking through a maze and using the Oculus Go head-mounted display (HMD) technology. The mechanics of the game require memorizing geometric shapes while the player progresses in two modes, autonomous or manual, with two levels of difficulty depending on the number of elements to remember. The application is developed in the Unity 3D video game engine considering the optimization of computational resources to improve the performance in the processing and maintaining adequate benefits for the user, while the generated data is stored and sent to a remote server. The maze task was assessed with 29 subjects in a controlled environment. The obtained results show a significant correlation between participants’ response accuracy in both the maze task and a face–pair test. Thus, the proposed task is able to perform memory assessments

The cupboard task: An immersive virtual reality-based system for everyday memory assessment

Background and objective Virtual Reality (VR) has the capacity to be used in cognitive rehabilitation interventions for diagnostic and training purposes. This technology allows the development of proposals that traditionally have been only implemented using physical elements that imply greater resources and a lesser degree of automation. This work presents an immersive virtual reality (IVR) application (the Cupboard task) for the evaluation of memory in a more ecological way and based on an activity of daily living (ADL). Methods To appraise its construct validity, we have carried out a comparative study with a traditional method of memory assessment (method of loci). To check for any association between performance and age, performance with years of education, and reaction time with age, the Pearson's correlation was used. One-way ANOVA was used to check for differences in performance by gender. We also performed a reliability analysis with a two way mixed effects model where people effects are random and measures effects are fixed. Therefore, intra-class correlation coefficient with absolute agreement was reckoned to assess the consistency or concordance of the measures made by both the method of loci and the cupboard IVR task. Results Both tasks were evaluated on a sample of 22 healthy participants who voluntarily took part in the experiment. The results obtained showed a high degree of concordance between both memory performance measures, which assumes good clinical relevance. In addition, other age-related effects were found, common to memory assessment tasks. Conclusions This work showed that it is possible to use an IVR application to successfully assess everyday memory. We have also demonstrated the potential of IVR to develop valid tests that assess memory functions reliably and efficiently and within ecologically valid contexts. The results obtained open the door to its use in clinical settings for cognitive training (and promoting cognitive health) of patients with mild cognitive impairment (MCI), severe cognitive impairment (SCI) such as Alzheimer or Dementia, etc., with full guarantees of application, although it must first be validated through a randomized control trial (RCT). The degree of usability of the Cupboard task was very high according to the test carried out by the participants

Promising developments in neuropsychological approaches for the detection of preclinical Alzheimer’s disease: a selective review

Recently published guidelines suggest that the most opportune time to treat individuals with Alzheimer’s disease is during the preclinical phase of the disease. This is a phase when individuals are defined as clinically normal but exhibit evidence of amyloidosis, neurodegeneration and subtle cognitive/behavioral decline. While our standard cognitive tests are useful for detecting cognitive decline at the stage of mild cognitive impairment, they were not designed for detecting the subtle cognitive variations associated with this biomarker stage of preclinical Alzheimer’s disease. However, neuropsychologists are attempting to meet this challenge by designing newer cognitive measures and questionnaires derived from translational efforts in neuroimaging, cognitive neuroscience and clinical/experimental neuropsychology. This review is a selective summary of several novel, potentially promising, approaches that are being explored for detecting early cognitive evidence of preclinical Alzheimer’s disease in presymptomatic individuals

Mutagen-Specific Mutation Signature Determines Global microRNA Binding

Micro-RNAs (miRNAs) are small non-coding RNAs that regulate gene products at the post-transcriptional level. It is thought that loss of cell regulation by miRNAs supports cancer development. Based on whole genome sequencing of a melanoma tumor, we predict, using three different computational algorithms, that the melanoma somatic mutations globally reduce binding of miRNAs to the mutated 3′UTRs. This phenomenon reflects the nature of the characteristic UV-induced mutation, C-to-T. Furthermore, we show that seed regions are enriched with Guanine, thus rendering miRNAs prone to reduced binding to UV-mutated 3′UTRs. Accordingly, mutation patterns in non UV-induced malignancies e.g. lung cancer and leukemia do not yield similar predictions. It is suggested that UV-induced disruption of miRNA-mediated gene regulation plays a carcinogenic role. Remarkably, dark-skinned populations have significantly higher GC content in 3′UTR SNPs than light-skinned populations, which implies on evolutionary pressure to preserve regulation by trans-acting oligonucleotides under conditions with excess UV radiation

Identification of RNA editing sites in the SNP database

The relationship between human inherited genomic variations and phenotypic differences has been the focus of much research effort in recent years. These studies benefit from millions of single-nucleotide polymorphism (SNP) records available in public databases, such as dbSNP. The importance of identifying false dbSNP records increases with the growing role played by SNPs in linkage analysis for disease traits. In particular, the emerging understanding of the abundance of DNA and RNA editing calls for a careful distinction between inherited SNPs and somatic DNA and RNA modifications. In order to demonstrate that some of the SNP database records are actually somatic modification, we focus on one type of these modifications, namely A-to-I RNA editing, and present evidence for hundreds of dbSNP records that are actually editing sites. We provide a list of 102 RNA editing sites previously annotated in dbSNP database as SNPs, and experimentally validate seven of these. Interestingly, we show how dbSNP can serve as a starting point to look for new editing sites. Our results, for this particular type of RNA editing, demonstrate the need for a careful analysis of SNP databases in light of the increasing recognition of the significance of somatic sequence modifications

Longitudinal Trajectories of the Cognitive Function Index in the A4 Study.

BACKGROUND: The Anti-Amyloid in Asymptomatic Alzheimers Disease (A4) Study failed to show a treatment benefit with solanezumab, but the longitudinal consequences of elevated amyloid were observed in study participants with objective decline on the Preclinical Alzheimer Cognitive Composite (PACC) and subjective decline on the combined Cognitive Function Index (participant + study partner CFI), during the trial period. OBJECTIVES: We sought to expand on previous findings by comparing longitudinal patterns of participant and study partner CFI separately and their associations with the PACC stratified by baseline amyloid tertile over the course of the A4 Study. DESIGN: Cognitively unimpaired older adult participants and their study partners were independently administered the CFI at screen prior to amyloid PET disclosure and then at 3 subsequent visits (week 48, week 168, week 240) of the study. PACC collected at visits concurrent with CFI administration were also examined longitudinally. SETTING: The A4 Study was conducted at 67 sites in Australia, Canada, Japan, and the United States. PARTICIPANTS: 1,147 participants with elevated amyloid based on florbetapir PET were enrolled in the A4 Study and included in these analyses. 583 were on placebo and 564 were treated with solanezumab. MEASUREMENTS: The PACC was used to assess objective cognitive performance and the CFI was used to assess change in everyday cognitive functioning by the participant and their study partner independently. Amyloid level was characterized by Centiloid tertiles (<46.1 CL, 46.1 to 77.2 CL, >77.2 CL). Participants were aware of their elevated amyloid status, but not their CL tertile, or specific level of amyloid. Longitudinal correlations between participant and study partner CFI and PACC were examined at all visits where assessments were available. The impact of baseline amyloid tertile on CFI and PACC associations was also examined. RESULTS: Both participant and study partner CFI increased over the duration of the study indicating worsening cognitive functioning. Results did not differ by treatment group. The association between higher CFI and worse PACC for both for participant and study partner became progressively stronger over the course of the study. PACC had a significantly higher correlation with study partner CFI than with participant CFI by week 168. The stronger correlations between study partner CFI and PACC were driven by those in the highest amyloid tertile. CONCLUSION: Both participant and study partner report captured subtle changes in everyday cognitive functioning for participants with biomarker confirmed and disclosed preclinical AD. Moreover, study partner report was most highly aligned with cognitive decline, particularly among those with the highest amyloid load