Background Visual impairment has been strongly associated with the incidence of dementia. Appropriate cognitive screening for the elderly with visual impairment is crucial for early identification of ...dementia and its management. Due to challenges in processing visually presented stimuli among participants, the cut-off score of the Hong Kong version of the Montreal Cognitive Assessment for the Visually Impaired (HKMoCA-VI), also known as MoCA-BLIND or MoCA-22, was unknown. Besides, the cognitive status of elderly with visual impairment residing in care homes is rarely investigated. The current study aimed to 1) establish the cut-off score for HKMoCA-VI and 2) examine the general cognitive functioning of elderly with visual impairment living in residential homes in Hong Kong in terms of MoCA-VI percentile scores. Method HKMoCA-VI and the Cantonese version of the Mini-Mental State Examination (CMMSE) were administered to 123 visually impaired elderly residents in care homes in Hong Kong. Percentile scores of HKMoCA-VI by age and education level were determined, and the concurrent validity, sensitivity, and specificity of HKMoCA-VI were assessed. Results A cut-off score 12 was suggested for HKMoCA-VI, which yielded a sensitivity and specificity of 89.29% and 83.58%, respectively. Moreover, it strongly correlated with CMMSE, indicating satisfactory concurrent validity. Conclusions HKMoCA-VI is suggested to be a viable cognitive screening tool for elderly individuals with visual impairment in residential homes. Further modifications to enhance the sensitivity and specificity of the measure are proposed.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Swallowing disorders, especially dysphagia, might lead to malnutrition and dehydration and could potentially lead to fatal aspiration. Benchmark swallowing assessments, such as videofluoroscopy or ...endoscopy, are expensive and invasive. Wearable technologies using acoustics and accelerometric sensors could offer opportunities for accessible and home-based long-term assessment. Identifying valid swallow events is the first step before enabling the technology for clinical applications. The objective of this review is to summarize the evidence of using acoustics-based and accelerometric-based wearable technology for swallow detection, in addition to their configurations, modeling, and assessment protocols. Two authors independently searched electronic databases, including PubMed, Web of Science, and CINAHL. Eleven (n = 11) articles were eligible for review. In addition to swallowing events, non-swallowing events were also recognized by dry (saliva) swallowing, reading, yawning, etc., while some attempted to classify the types of swallowed foods. Only about half of the studies reported that the device attained an accuracy level of >90%, while a few studies reported poor performance with an accuracy of <60%. The reviewed articles were at high risk of bias because of the small sample size and imbalanced class size problem. There was high heterogeneity in assessment protocol that calls for standardization for swallowing, dry-swallowing and non-swallowing tasks. There is a need to improve the current wearable technology and the credibility of relevant research for accurate swallowing detection before translating into clinical screening for dysphagia and other swallowing disorders.
Dysphagia is one of the most common problems among older adults, which might lead to aspiration pneumonia and eventual death. It calls for a feasible, reliable, and standardized screening or ...assessment method to prompt rehabilitation measures and mitigate the risks of dysphagia complications. Computer-aided screening using wearable technology could be the solution to the problem but is not clinically applicable because of the heterogeneity of assessment protocols. The aim of this paper is to formulate and unify a swallowing assessment protocol, named the Comprehensive Assessment Protocol for Swallowing (CAPS), by integrating existing protocols and standards. The protocol consists of two phases: the pre-test phase and the assessment phase. The pre-testing phase involves applying different texture or thickness levels of food/liquid and determining the required bolus volume for the subsequent assessment. The assessment phase involves dry (saliva) swallowing, wet swallowing of different food/liquid consistencies, and non-swallowing (e.g., yawning, coughing, speaking, etc.). The protocol is designed to train the swallowing/non-swallowing event classification that facilitates future long-term continuous monitoring and paves the way towards continuous dysphagia screening.
Heterogeneity in Sjögren's syndrome (SS), increasingly called Sjögren's disease, suggests the presence of disease subtypes, which poses a major challenge for the diagnosis, management, and treatment ...of this autoimmune disorder. Previous work distinguished patient subgroups based on clinical symptoms, but it is not clear to what extent symptoms reflect underlying pathobiology. The purpose of this study was to discover clinical meaningful subtypes of SS based on genome-wide DNA methylation data. We performed a cluster analysis of genome-wide DNA methylation data from labial salivary gland (LSG) tissue collected from 64 SS cases and 67 non-cases. Specifically, hierarchical clustering was performed on low dimensional embeddings of DNA methylation data extracted from a variational autoencoder to uncover unknown heterogeneity. Clustering revealed clinically severe and mild subgroups of SS. Differential methylation analysis revealed that hypomethylation at the MHC and hypermethylation at other genome regions characterize the epigenetic differences between these SS subgroups. Epigenetic profiling of LSGs in SS yields new insights into mechanisms underlying disease heterogeneity. The methylation patterns at differentially methylated CpGs are different in SS subgroups and support the role of epigenetic contributions to the heterogeneity in SS. Biomarker data derived from epigenetic profiling could be explored in future iterations of the classification criteria for defining SS subgroups.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Differential methylation of immune genes has been a consistent theme observed in Sjögren's syndrome (SS) in CD4+ T cells, CD19+ B cells, whole blood, and labial salivary glands (LSGs). Multiple ...studies have found associations supporting genetic control of DNA methylation in SS, which in the absence of reverse causation, has positive implications for the potential of epigenetic therapy. However, a formal study of the causal relationship between genetic variation, DNA methylation, and disease status is lacking. We performed a causal mediation analysis of DNA methylation as a mediator of nearby genetic association with SS using LSGs and genotype data collected from 131 female members of the Sjögren's International Collaborative Clinical Alliance registry, comprising of 64 SS cases and 67 non-cases. Bumphunter was used to first identify differentially-methylated regions (DMRs), then the causal inference test (CIT) was applied to identify DMRs mediating the association of nearby methylation quantitative trait loci (MeQTL) with SS. Bumphunter discovered 215 DMRs, with the majority located in the major histocompatibility complex (MHC) on chromosome 6p21.3. Consistent with previous findings, regions hypomethylated in SS cases were enriched for gene sets associated with immune processes. Using the CIT, we observed a total of 19 DMR-MeQTL pairs that exhibited strong evidence for a causal mediation relationship. Close to half of these DMRs reside in the MHC and their corresponding meQTLs are in the region spanning the HLA-DQA1, HLA-DQB1, and HLA-DQA2 loci. The risk of SS conferred by these corresponding MeQTLs in the MHC was further substantiated by previous genome-wide association study results, with modest evidence for independent effects. By validating the presence of causal mediation, our findings suggest both genetic and epigenetic factors contribute to disease susceptibility, and inform the development of targeted epigenetic modification as a therapeutic approach for SS.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Multiple sclerosis (MS) is an autoimmune disease with high prevalence among populations of northern European ancestry. Past studies have shown that exposure to ultraviolet radiation could explain the ...difference in MS prevalence across the globe. In this study, we investigate whether the difference in MS prevalence could be explained by European genetic risk factors. We characterized the ancestry of MS-associated alleles using RFMix, a conditional random field parameterized by random forests, to estimate their local ancestry in the largest assembled admixed population to date, with 3,692 African Americans, 4,915 Asian Americans, and 3,777 Hispanics. The majority of MS-associated human leukocyte antigen (HLA) alleles, including the prominent HLA-DRB1*15:01 risk allele, exhibited cosmopolitan ancestry. Ancestry-specific MS-associated HLA alleles were also identified. Analysis of the HLA-DRB1*15:01 risk allele in African Americans revealed that alleles on the European haplotype conferred three times the disease risk compared to those on the African haplotype. Furthermore, we found evidence that the European and African HLA-DRB1*15:01 alleles exhibit single nucleotide polymorphism (SNP) differences in regions encoding the HLA-DRB1 antigen-binding heterodimer. Additional evidence for increased risk of MS conferred by the European haplotype were found for HLA-B*07:02 and HLA-A*03:01 in African Americans. Most of the 200 non-HLA MS SNPs previously established in European populations were not significantly associated with MS in admixed populations, nor were they ancestrally more European in cases compared to controls. Lastly, a genome-wide search of association between European ancestry and MS revealed a region of interest close to the ZNF596 gene on chromosome 8 in Hispanics; cases had a significantly higher proportion of European ancestry compared to controls. In conclusion, our study established that the genetic ancestry of MS-associated alleles is complex and implicated that difference in MS prevalence could be explained by the ancestry of MS-associated alleles.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Thermal comfort is a major issue in cities and it is expected to change in the future due to the changing climate. The objective of this paper is to use the universal thermal comfort index (UTCI) to ...compare the outdoor thermal comfort in Hong Kong in the past (1971–2000) and the future (2046–2065 and 2081–2100). The future climate of Hong Kong was determined by the general circulation model (GCM) simulations of future climate scenarios (A1B and B1) established by the Intergovernmental Panel on Climate Change (IPCC). Three GCMs were chosen, GISS-ER, GFDL-CM2.1 and MRI-CGCM2.3.2, based on their performance in simulating past climate. Through a statistical downscaling procedure, the future climatic variables were transferred to the local scale. The UTCI is calculated by four predicted climate variables: air temperature, wind speed, relative humidity and solar radiation. After a normalisation procedure, future UTCI profiles for the urban area of Hong Kong were created. Comparing the past UTCI (calculated by observation data) and future UTCI, all three GCMs predicted that the future climate scenarios have a higher mode and a higher maximum value. There is a shift from ‘No Thermal Stress’ toward ‘Moderate Heat Stress’ and ‘Strong Heat Stress’ during the period 2046–2065, becoming more severe for the later period (2081–2100). Comparing the two scenarios, B1 exhibited similar projections in the two time periods whereas for A1B there was a significant difference, with both the mode and maximum increasing by 2 °C from 2046–2065 to 2081–2100.
Abstract
Motivation
In pharmacogenomic studies, the biological context of cell lines influences the predictive ability of drug-response models and the discovery of biomarkers. Thus, similar cell ...lines are often studied together based on prior knowledge of biological annotations. However, this selection approach is not scalable with the number of annotations, and the relationship between gene–drug association patterns and biological context may not be obvious.
Results
We present a procedure to compare cell lines based on their gene–drug association patterns. Starting with a grouping of cell lines from biological annotation, we model gene–drug association patterns for each group as a bipartite graph between genes and drugs. This is accomplished by applying sparse canonical correlation analysis (SCCA) to extract the gene–drug associations, and using the canonical vectors to construct the edge weights. Then, we introduce a nuclear norm-based dissimilarity measure to compare the bipartite graphs. Accompanying our procedure is a permutation test to evaluate the significance of similarity of cell line groups in terms of gene–drug associations. In the pharmacogenomic datasets CTRP2, GDSC2 and CCLE, hierarchical clustering of carcinoma groups based on this dissimilarity measure uniquely reveals clustering patterns driven by carcinoma subtype rather than primary site. Next, we show that the top associated drugs or genes from SCCA can be used to characterize the clustering patterns of haematopoietic and lymphoid malignancies. Finally, we confirm by simulation that when drug responses are linearly dependent on expression, our approach is the only one that can effectively infer the true hierarchy compared to existing approaches.
Availability and implementation
Bipartite graph-based hierarchical clustering is implemented in R and can be obtained from CRAN: https://CRAN.R-project.org/package=hierBipartite. The source code is available at https://github.com/CalvinTChi/hierBipartite. The datasets were derived from sources in the public domain, which are the Cancer Cell Line Encyclopedia (https://portals.broadinstitute.org/ccle), the Cancer Therapeutics Response Portal (https://portals.broadinstitute.org/ctrp.v2.1/?page=#ctd2BodyHome), and the Genomics of Drug Sensitivity in Cancer (https://www.cancerrxgene.org/). These datasets can be downloaded using the PharmacoGx R package (https://bioconductor.org/packages/release/bioc/html/PharmacoGx.html).
Supplementary information
Supplementary data are available at Bioinformatics online.
Visual impairment has been strongly associated with the incidence of dementia. Appropriate cognitive screening for the elderly with visual impairment is crucial for early identification of dementia ...and its management. Due to challenges in processing visually presented stimuli among participants, the cut-off score of the Hong Kong version of the Montreal Cognitive Assessment for the Visually Impaired (HKMoCA-VI), also known as MoCA-BLIND or MoCA-22, was unknown. Besides, the cognitive status of elderly with visual impairment residing in care homes is rarely investigated. The current study aimed to 1) establish the cut-off score for HKMoCA-VI and 2) examine the general cognitive functioning of elderly with visual impairment living in residential homes in Hong Kong in terms of MoCA-VI percentile scores. HKMoCA-VI and the Cantonese version of the Mini-Mental State Examination (CMMSE) were administered to 123 visually impaired elderly residents in care homes in Hong Kong. Percentile scores of HKMoCA-VI by age and education level were determined, and the concurrent validity, sensitivity, and specificity of HKMoCA-VI were assessed. A cut-off score 12 was suggested for HKMoCA-VI, which yielded a sensitivity and specificity of 89.29% and 83.58%, respectively. Moreover, it strongly correlated with CMMSE, indicating satisfactory concurrent validity. HKMoCA-VI is suggested to be a viable cognitive screening tool for elderly individuals with visual impairment in residential homes. Further modifications to enhance the sensitivity and specificity of the measure are proposed.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
PDF
