Genetic study of multimodal imaging Alzheimer’s disease progression score implicates novel loci

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A Multilingual Handwriting Learning System for Visually Impaired People

Visually impaired people have previously been brought into learning and educational systems through various forms of assistive technology, such as haptic feedback systems. Haptic systems generally need expensive equipment and support from sighted teachers. Moreover, the learning has always been carried out with letters of different alphabets mapped into some tactile pattern. Writing is a big concern for the visually impaired as most official work, like signing, is still carried out by conventional handwriting methods. Most of the existing systems are limited to teaching a single language’s alphabet and basic grammar or may not provide feedback to let the learners know of their learning progress. Therefore, the objectives of this research are to develop an efficient system that includes voice-over guidance to teach writing in multiple alphabets to visually impaired people and to evaluate the performance of the proposed system. As such, a system was developed for teaching multilingual alphabets to visually impaired people with voice instructions. With the aid of a voice-over guide, learners were able to write letters with a stylus on a graphics pad. The progress assessment of the learners is carried out by an image processing algorithm and scored by a machine learning (ML) model. The Random Forest model was used due to its high accuracy (f1-score of 99.8% on test data) among the existing ten different ML algorithms. Finally, the performance and usability of this system were evaluated through an empirical study replicated with 16 participants, including four teachers and twelve visually impaired people. It was found that visually impaired people made fewer attempts to learn handwriting with the proposed system than with the normal handwriting teaching system. 100% of the participants agreed to recommend the system in the future

Genetic polymorphisms associated with adverse pregnancy outcomes in nulliparas.

Adverse pregnancy outcomes (APOs) affect a large proportion of pregnancies and represent an important cause of morbidity and mortality worldwide. Yet the pathophysiology of APOs is poorly understood, limiting our ability to prevent and treat these conditions. To search for genetic markers of maternal risk for four APOs, we performed multi-ancestry genome-wide association studies (GWAS) for pregnancy loss, gestational length, gestational diabetes, and preeclampsia. We clustered participants by their genetic ancestry and focused our analyses on three sub-cohorts with the largest sample sizes: European, African, and Admixed American. Association tests were carried out separately for each sub-cohort and then meta-analyzed together. Two novel loci were significantly associated with an increased risk of pregnancy loss: a cluster of SNPs located downstream of the TRMU gene (top SNP: rs142795512), and the SNP rs62021480 near RGMA. In the GWAS of gestational length we identified two new variants, rs2550487 and rs58548906 near WFDC1 and AC005052.1, respectively. Lastly, three new loci were significantly associated with gestational diabetes (top SNPs: rs72956265, rs10890563, rs79596863), located on or near ZBTB20, GUCY1A2, and RPL7P20, respectively. Fourteen loci previously correlated with preterm birth, gestational diabetes, and preeclampsia were found to be associated with these outcomes as well

Shifting From Active to Passive Monitoring of Alzheimer Disease: The State of the Research

ABSTRACT Most research using digital technologies builds on existing methods for staff‐administered evaluation, requiring a large investment of time, effort, and resources. Widespread use of personal mobile devices provides opportunities for continuous health monitoring without active participant engagement. Home‐based sensors show promise in evaluating behavioral features in near real time. Digital technologies across these methodologies can detect precise measures of cognition, mood, sleep, gait, speech, motor activity, behavior patterns, and additional features relevant to health. As a neurodegenerative condition with insidious onset, Alzheimer disease and other dementias (AD/D) represent a key target for advances in monitoring disease symptoms. Studies to date evaluating the predictive power of digital measures use inconsistent approaches to characterize these measures. Comparison between different digital collection methods supports the use of passive collection methods in settings in which active participant engagement approaches are not feasible. Additional studies that analyze how digital measures across multiple data streams can together improve prediction of cognitive impairment and early‐stage AD are needed. Given the long timeline of progression from normal to diagnosis, digital monitoring will more easily make extended longitudinal follow‐up possible. Through the American Heart Association–funded Strategically Focused Research Network, the Boston University investigative team deployed a platform involving a wide range of technologies to address these gaps in research practice. Much more research is needed to thoroughly evaluate limitations of passive monitoring. Multidisciplinary collaborations are needed to establish legal and ethical frameworks for ensuring passive monitoring can be conducted at scale while protecting privacy and security, especially in vulnerable populations

Phenotypic Heterogeneity among GBA p.R202X Carriers in Lewy Body Spectrum Disorders

: We describe the clinical and neuropathologic features of patients with Lewy body spectrum disorder (LBSD) carrying a nonsense variant, c.604C>T; p.R202X, in the glucocerebrosidase 1 (GBA) gene. While this GBA variant is causative for Gaucher's disease, the pathogenic role of this mutation in LBSD is unclear. Detailed neuropathologic evaluation was performed for one index case and a structured literature review of other GBA p.R202X carriers was conducted. Through the systematic literature search, we identified three additional reported subjects carrying the same GBA mutation, including one Parkinson's disease (PD) patient with early disease onset, one case with neuropathologically-verified LBSD, and one unaffected relative of a Gaucher's disease patient. Among the affected subjects carrying the GBA p.R202X, all males were diagnosed with Lewy body dementia, while the two females presented as PD. The clinical penetrance of GBA p.R202X in LBSD patients and families argues strongly for a pathogenic role for this variant, although presenting with a striking phenotypic heterogeneity of clinical and pathological features

Induction of systemic, mucosal and memory antibody responses targeting Vibrio cholerae O1 O-specific polysaccharide (OSP) in adults following oral vaccination with an oral killed whole cell cholera vaccine in Bangladesh.

BackgroundOral cholera vaccine (OCV) containing killed Vibrio cholerae O1 and O139 organisms (Bivalent-OCV; Biv-OCV) are playing a central role in global cholera control strategies. OCV is currently administered in a 2-dose regimen (day 0 and 14). There is a growing body of evidence that immune responses targeting the O-specific polysaccharide (OSP) of V. cholerae mediate protection against cholera. There are limited data on anti-OSP responses in recipients of Biv-OCV. We assessed serum antibody responses against O1 OSP, as well as antibody secreting cell (ASC) responses (a surrogate marker for mucosal immunity) and memory B cell responses in blood of adult recipients of Biv-OCV in Dhaka, Bangladesh.Methodology/principal findingsWe enrolled 30 healthy adults in this study and administered two doses of OCV (Shanchol) at days 0 and 14. Blood samples were collected before vaccination (day 0) and 7 days after each vaccination (day 7 and day 21), as well as on day 44. Serum responses were largely IgA with minimal IgG and IgM responses in this population. There was no appreciable boosting following day 14 vaccination. There were significant anti-OSP IgA ASC responses on day 7 following the first vaccination, but none after the second immunization. Anti-OSP IgA memory B cell responses were detectable 30 days after completion of the vaccination series, with no evident induction of IgG memory responses. In this population, anti-Ogawa OSP responses were more prominent than anti-Inaba responses, perhaps reflecting impact of previous exposure. Serum anti-OSP responses returned to baseline within 30 days of completing the vaccine series.ConclusionOur results call into question the utility of the 2-dose regimen separated by 14 days in adults in cholera endemic areas, and also suggest that Biv-OCV-induced immune responses targeting OSP are largely IgA in this highly endemic cholera area. Studies in children in cholera-endemic areas need to be performed. Protective efficacy that extends for more than a month after vaccination presumably is mediated by direct mucosal immune response which is not assessed in this study. Our results suggest a single dose of OCV in adults in a cholera endemic zone may be sufficient to mediate at least short-term protection