264 results on '"Y. Mok"'
Search Results
2. CRISPR-free base editors with enhanced activity and expanded targeting scope in mitochondrial and nuclear DNA
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Beverly Y. Mok, Anna V. Kotrys, Aditya Raguram, Tony P. Huang, Vamsi K. Mootha, and David R. Liu
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Biomedical Engineering ,Molecular Medicine ,Bioengineering ,Applied Microbiology and Biotechnology ,Biotechnology - Abstract
The all-protein cytosine base editor DdCBE uses TALE proteins and a double-stranded DNA-specific cytidine deaminase (DddA) to mediate targeted C•G-to-T•A editing. To improve editing efficiency and overcome the strict TC sequence-context constraint of DddA, we used phage-assisted non-continuous and continuous evolution to evolve DddA variants with improved activity and expanded targeting scope. Compared to canonical DdCBEs, base editors with evolved DddA6 improved mitochondrial DNA (mtDNA) editing efficiencies at TC by 3.3-fold on average. DdCBEs containing evolved DddA11 offered a broadened HC (H = A, C or T) sequence compatibility for both mitochondrial and nuclear base editing, increasing average editing efficiencies at AC and CC targets from less than 10% for canonical DdCBE to 15–30% and up to 50% in cell populations sorted to express both halves of DdCBE. We used these evolved DdCBEs to efficiently install disease-associated mtDNA mutations in human cells at non-TC target sites. DddA6 and DddA11 substantially increase the effectiveness and applicability of all-protein base editing.
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- 2022
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3. Application of virtual reality for peritoneal dialysis exchange learning in patients with end-stage renal disease and cognitive impairment
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Connie M. S. Lee, Kenneth N. K. Fong, Maggie M. Y. Mok, M. K. Lam, Y. Kung, Paven P. W. Chan, Maggie K. M. Ma, S. L. Lui, Lorraine P. Y. Kwan, W. L. Chu, P. C. Hui, Christina S. F. Yau, Ivan W. L. Kwan, Kelsey Y. M. Chan, and T. M. Chan
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Human-Computer Interaction ,Computer Graphics and Computer-Aided Design ,Software - Abstract
Cognitive impairment is not uncommon in patients with end-stage renal disease and can make it more difficult for these patients to carry out peritoneal dialysis (PD) on their own. Their attempts to do so may result in adverse consequences such as peritonitis. PD exchange is a complex procedure demanding knowledge and skill which requires close supervision and guidance by a renal nurse specialist. In this study, a non-immersive virtual reality (VR) training program using a Leap motion hand tracking device was developed to facilitate patients' understanding and learning of the PD exchange procedure before attempting real task practice. This study was a two-center single-blinded randomized controlled trial on 23 incident PD patients. Patients in the experimental group received 8 sessions of VR training, while patients in the control were provided with printed educational materials. The results showed that there were significant differences between the two groups in performance of the overall PD exchange sequence, especially on the crucial steps. VR had a patient satisfaction rate of 89%, and all patients preferred to have the VR aid incorporated in PD training. Our findings conclude VR can be a useful aid in the training and reinforcement of PD exchange procedures, with distinct merits of being free from restrictions of time, space, and manpower.
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- 2022
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4. Large‐scale plasma proteomic profiling identifies a high‐performance biomarker panel for Alzheimer's disease screening and staging
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Estella P.S. Tong, Henrik Zetterberg, John Hardy, Amy K.Y. Fu, Fanny C.F. Ip, Ronnie M. N. Lo, Vincent Mok, Kin Y. Mok, Andrew Lung-Tat Chan, Xiaopu Zhou, Bonnie W.Y. Wong, Kit Cheung, Yu Chen, Timothy Kwok, Nancy Y. Ip, Yuanbing Jiang, Nicole C. H. Lai, and Philip C.H. Chan
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Proteomics ,0301 basic medicine ,Amyloid ,Endophenotypes ,Epidemiology ,tau Proteins ,Disease ,Computational biology ,Cohort Studies ,03 medical and health sciences ,Cellular and Molecular Neuroscience ,0302 clinical medicine ,Developmental Neuroscience ,Disease Screening ,Alzheimer Disease ,medicine ,Humans ,Mass Screening ,Phosphorylation ,Aged ,Amyloid beta-Peptides ,business.industry ,Proteomic Profiling ,Health Policy ,Neurodegeneration ,Area under the curve ,Reproducibility of Results ,Middle Aged ,medicine.disease ,Blood proteins ,3. Good health ,Psychiatry and Mental health ,030104 developmental biology ,Proteome ,Hong Kong ,Neurology (clinical) ,Geriatrics and Gerontology ,business ,Biomarkers ,030217 neurology & neurosurgery - Abstract
Introduction Blood proteins are emerging as candidate biomarkers for Alzheimer's disease (AD). We systematically profiled the plasma proteome to identify novel AD blood biomarkers and develop a high-performance, blood-based test for AD. Methods We quantified 1160 plasma proteins in a Hong Kong Chinese cohort by high-throughput proximity extension assay and validated the results in an independent cohort. In subgroup analyses, plasma biomarkers for amyloid, tau, phosphorylated tau, and neurodegeneration were used as endophenotypes of AD. Results We identified 429 proteins that were dysregulated in AD plasma. We selected 19 "hub proteins" representative of the AD plasma protein profile, which formed the basis of a scoring system that accurately classified clinical AD (area under the curve = 0.9690-0.9816) and associated endophenotypes. Moreover, specific hub proteins exhibit disease stage-dependent dysregulation, which can delineate AD stages. Discussion This study comprehensively profiled the AD plasma proteome and serves as a foundation for a high-performance, blood-based test for clinical AD screening and staging.
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- 2021
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5. Conversion from Aranesp® to <scp>NESP</scp> ® in dialysis patients—Exploration of dosing strategies and the feasibility of extending the dosing interval
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Desmond Y H Yap, Maggie K.M. Ma, Maggie M Y Mok, Lorraine P Y Kwan, Tak Mao Chan, Cindy B.Y. Choy, Angela Yee-Moon Wang, Gary C.W. Chan, and Sydney C.W. Tang
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Male ,medicine.medical_specialty ,Darbepoetin alfa ,Anemia ,medicine.medical_treatment ,Urology ,Drug Administration Schedule ,Drug Costs ,Group B ,Peritoneal dialysis ,Cohort Studies ,Hemoglobins ,Renal Dialysis ,medicine ,Humans ,Dosing ,Dialysis ,Aged ,business.industry ,General Medicine ,Middle Aged ,medicine.disease ,Nephrology ,Erythropoietin ,Hematinics ,Feasibility Studies ,Kidney Failure, Chronic ,Female ,business ,medicine.drug ,Cohort study - Abstract
AIM Darbepoetin alpha is available as Aranesp® and NESP®, which differ in the inactive component and maximum dose-strength of prefilled syringes. We conducted an observational cohort study to investigate optimal conversion strategies and the feasibility of extending dosing intervals with higher-dose preparations in dialysis patients converting from Aranesp® to NESP®. METHODS Adult dialysis patients on Aranesp® with stable haemoglobin of 9-12 g/dL were converted to NESP® at the same monthly total dose according to one of three conversion regimens. Group A included patients on ≤80 mcg/month of Aranesp® who converted with dosing regimen unchanged. Group B patients converted to NESP® with extended dosing intervals using higher individual dose preparations. Group C were patients on 100 mcg Aranesp® who converted to NESP® 120 mcg with extended dosing intervals. Patients were observed for 6 months. RESULTS Fifty patients were included. All 24 Group A patients maintained stable haemoglobin. In Group B, 10 patients (50%) maintained stable haemoglobin with extension of dosing interval from 1.04 ± 0.14 to 3.03 ± 1.28 weeks. Factors associated with success in extending dosing interval included a lower prevalence of cardiovascular disease and a higher Kt/Vurea in peritoneal dialysis patients. Four patients (80%) in Group C maintained stable haemoglobin after conversion to NESP® 120 mcg with extended dosing interval. The use of NESP® 120 mcg was well tolerated, and was associated with reduced patient-reported pain score and 38% reduction of drug cost. CONCLUSION Dialysis patients on Aranesp® can be successfully converted to NESP® and the dosing interval can be extended successfully in a significant proportion of patients, which could reduce discomfort and drug cost.
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- 2021
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6. Lipoprotein-X: A Case of Falsely Elevated LDL Hypercholesterolemia
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Jacob Y. Mok and Jaime Burkle
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Case Report ,Cardiology and Cardiovascular Medicine - Abstract
Lipoprotein-X is an extremely rare cause of severe hyperlipidemia. We present a case of a 26-year-old man with primary sclerosing cholangitis who developed lipoprotein X-induced pseudohyponatremia with severe hyponatremia. In this case report, we also discuss the diagnostic approach and the treatment for lipoprotein X. (Level of Difficulty: Advanced.)
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- 2023
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7. The impacts of daily movements on uniform clothing fit – an interview study
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Ningrong Xie and P. Y. Mok
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Visual Arts and Performing Arts ,Work (electrical) ,business.industry ,Applied psychology ,Interview study ,Psychology ,Clothing ,business ,Affect (psychology) ,Industrial and Manufacturing Engineering ,Education - Abstract
Little is known about how people’s routine body movements when they are at work affect the perceived fit and comfort of their uniform/workwear. This knowledge gap was addressed in this study throug...
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- 2021
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8. Multi‐Omics‐Based Autophagy‐Related Untypical Subtypes in Patients with Cerebral Amyloid Pathology
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Jong‐Chan Park, Natalia Barahona‐Torres, So‐Yeong Jang, Kin Y. Mok, Haeng Jun Kim, Sun‐Ho Han, Kwang‐Hyun Cho, Xiaopu Zhou, Amy K. Y. Fu, Nancy Y. Ip, Jieun Seo, Murim Choi, Hyobin Jeong, Daehee Hwang, Dong Young Lee, Min Soo Byun, Dahyun Yi, Jong Won Han, Inhee Mook‐Jung, and John Hardy
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Amyloid beta-Peptides ,General Chemical Engineering ,General Engineering ,General Physics and Astronomy ,Medicine (miscellaneous) ,Amyloidogenic Proteins ,Amyloidosis ,Biochemistry, Genetics and Molecular Biology (miscellaneous) ,Alzheimer Disease ,Autophagy ,Leukocytes, Mononuclear ,Humans ,General Materials Science ,Microglia - Abstract
Recent multi-omics analyses paved the way for a comprehensive understanding of pathological processes. However, only few studies have explored Alzheimer's disease (AD) despite the possibility of biological subtypes within these patients. For this study, unsupervised classification of four datasets (genetics, miRNA transcriptomics, proteomics, and blood-based biomarkers) using Multi-Omics Factor Analysis+ (MOFA+), along with systems-biological approaches following various downstream analyses are performed. New subgroups within 170 patients with cerebral amyloid pathology (Aβ+) are revealed and the features of them are identified based on the top-rated targets constructing multi-omics factors of both whole (M-TPAD) and immune-focused models (M-IPAD). The authors explored the characteristics of subtypes and possible key-drivers for AD pathogenesis. Further in-depth studies showed that these subtypes are associated with longitudinal brain changes and autophagy pathways are main contributors. The significance of autophagy or clustering tendency is validated in peripheral blood mononuclear cells (PBMCs; n = 120 including 30 Aβ- and 90 Aβ+), induced pluripotent stem cell-derived human brain organoids/microglia (n = 12 including 5 Aβ-, 5 Aβ+, and CRISPR-Cas9 apolipoprotein isogenic lines), and human brain transcriptome (n = 78). Collectively, this study provides a strategy for precision medicine therapy and drug development for AD using integrative multi-omics analysis and network modelling.
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- 2022
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9. An eight country cross-sectional study of the psychosocial effects of COVID-19 induced quarantine and/or isolation during the pandemic
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Philip J. Schluter, Mélissa Généreux, Elsa Landaverde, Emily Y. Y. Chan, Kevin K. C. Hung, Ronald Law, Catherine P. Y. Mok, Virginia Murray, Tracey O’Sullivan, Zeeshan Qadar, and Mathieu Roy
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Adult ,Depressive Disorder, Major ,Multidisciplinary ,Cross-Sectional Studies ,Depression ,Communicable Disease Control ,Quarantine ,COVID-19 ,Humans ,Anxiety ,Pandemics - Abstract
Forced quarantine and nationwide lockdowns have been a primary response by many jurisdictions in their attempt at COVID-19 elimination or containment, yet the associated mental health burden is not fully understood. Using an eight country cross-sectional design, this study investigates the association between COVID-19 induced quarantine and/or isolation on probable generalized anxiety disorder (GAD) and major depressive episode (MDE) psychological outcomes approximately eight months after the pandemic was declared. Overall, 9027 adults participated, and 2937 (32.5%) were indicated with GAD and/or MDE. Reported quarantine and/or isolation was common, with 1199 (13.8%) confined for travel or health requirements, 566 (6.5%) for being close contact, 720 (8.3%) for having COVID-19 symptoms, and 457 (5.3%) for being COVID-19 positive. Compared to those not quarantining or isolating, the adjusted estimated relative risks of GAD and/or MDE associated with quarantine and/or isolation was significant (p
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- 2022
10. Phaeohyphomycosis due to Veronaea botryosa in cultured white sturgeon ( Acipenser transmontanus Richardson) from California USA during 2006 to 2015
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Brian L. Wickes, Steven V. Kubiski, Thomas B. Waltzek, E. Scott Weber, Barbara A. Byrne, Adam O. Michel, Lori A. Campbell, Galaxia Cortés-Hinojosa, Joseph M. Groff, and Mai Y. Mok
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Male ,0301 basic medicine ,Veterinary (miscellaneous) ,Zoology ,Fungus ,Aquatic Science ,California ,Fish Diseases ,03 medical and health sciences ,Sturgeon ,Ascomycota ,medicine ,Animals ,Juvenile ,Internal transcribed spacer ,biology ,Zoonosis ,Fishes ,04 agricultural and veterinary sciences ,Acipenser baerii ,medicine.disease ,biology.organism_classification ,Phaeohyphomycosis ,030104 developmental biology ,Acipenser transmontanus ,040102 fisheries ,0401 agriculture, forestry, and fisheries ,Female - Abstract
Infection with Veronaea botryosa can result in rare cutaneous or disseminated, granulomatous to pyogranulomatous phaeohyphomycosis in humans, although disease due to the fungus has also been reported in non-mammalian vertebrates. This report documents disease due to V. botryosa in captive, juvenile to subadult or young adult white sturgeon (Acipenser transmontanus Richardson) from California USA and complements a previous report of the disease in captive Siberian sturgeon (Acipenser baerii) from Florida USA. Pathological examinations revealed granulomatous to pyogranulomatous inflammation of multiple organs. Isolates of the fungal agent were phenotypically consistent with V. botryosa, and molecular analyses of the D1/D2 region of the fungal 28S rRNA gene and the internal transcribed spacer (ITS) region located between the fungal 18S and 28S rRNA genes confirmed the aetiologic agent as V. botryosa. The disease in captive sturgeon results in a considerable economic encumbrance to the producer due to the loss of the cumulative financial resources invested in the production of older subadult to young adult sturgeon.
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- 2020
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11. End-of-life programme for older care home residents: an evaluation study
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WC Ng, Winnie W Y Mok, James Kh Luk, Felix Hw Chan, Wai Kwong Chan, Tuen-Ching Chan, and Fei Chan
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- 2020
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12. Direct Renin Inhibition in Non-diabetic chronic Kidney disease (DRINK): a prospective randomized trial
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Maggie M Y Mok, Desmond Y H Yap, Dennis K. M. Ip, Kar Neng Lai, Gary C.W. Chan, Maggie K.M. Ma, Kam Wa Chan, Sydney C.W. Tang, and Sidney Tam
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Adult ,medicine.medical_specialty ,Hyperkalemia ,medicine.drug_class ,Urology ,Renal function ,Angiotensin-Converting Enzyme Inhibitors ,Renin inhibitor ,Angiotensin Receptor Antagonists ,chemistry.chemical_compound ,Renin ,medicine ,Humans ,Prospective Studies ,Renal Insufficiency, Chronic ,Aged ,Transplantation ,Creatinine ,business.industry ,Surrogate endpoint ,Hazard ratio ,Middle Aged ,Aliskiren ,medicine.disease ,chemistry ,Nephrology ,medicine.symptom ,business ,Glomerular Filtration Rate ,Kidney disease - Abstract
Background The potential long-term safety and efficacy of aliskiren in nondiabetic chronic kidney disease (CKD) are unknown. We sought to investigate the renoprotective effect of aliskiren on nondiabetic CKD patients. Methods In this open-label, parallel, randomized controlled trial, nondiabetic CKD Stages 3–4 patients were randomized to receive aliskiren added to an angiotensin II receptor blocker (ARB) at the maximal tolerated dose, or ARB alone. Primary outcome was the rate of change in estimated glomerular filtration rate (eGFR). Secondary endpoints included rate of change in urine protein-to-creatinine ratio (UPCR), cardiovascular events and hyperkalemia. Composite renal outcomes of doubling of baseline serum creatinine or a 40% reduction in eGFR or incident end-stage renal disease or death were analyzed as post hoc analysis. Results Seventy-six patients were randomized: 37 to aliskiren (mean age 55.1 ± 11.1 years) and 39 to control (mean age 55.0 ± 9.4 years). Their baseline demographics were comparable to eGFR (31.9 ± 9.0 versus 27.7 ± 9.0 mL/min/1.73 m2, P = 0.05) and UPCR (30.7 ± 12.6 versus 47.8 ± 2.8 mg/mmol, P = 0.33) for treatment versus control subjects. After 144 weeks of follow-up, there was no difference in the rate of eGFR change between groups. Six patients in the aliskiren group and seven in the control group reached the renal composite endpoint (16.2% versus 17.9%, P = 0.84). The cardiovascular event rate was 10.8% versus 2.6% (P = 0.217). The hyperkalemia rate was 18.9% versus 5.1% with an adjusted hazard ratio of 7.71 (95% confidence interval 1.14 to 52.3, P = 0.04) for the aliskiren arm. Conclusion Aliskiren neither conferred additional renoprotective benefit nor increased adverse events, except for more hyperkalemia in nondiabetic CKD patients.
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- 2020
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13. A high‐performance biomarker panel for Alzheimer’s disease screening and staging identified by large‐scale plasma proteomic profiling
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Yuanbing Jiang, Xiaopu Zhou, Fanny C.F. Ip, Philip Chan, Yu Chen, Nicole Chit Hang Lai, Kit Cheung, Ronnie M.N. Lo, Estella Pui‐Sze Tong, Bonnie W.Y. Wong, Andrew L.T. Chan, Vincent C.T. Mok, Timothy C.Y. Kwok, Kin Y. Mok, John Hardy, Henrik Zetterberg, Amy K.Y. Fu, and Nancy Y. Ip
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Psychiatry and Mental health ,Cellular and Molecular Neuroscience ,Developmental Neuroscience ,Epidemiology ,Health Policy ,Neurology (clinical) ,Geriatrics and Gerontology - Published
- 2021
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14. CRISPR-free base editors with enhanced activity and expanded targeting scope in mitochondrial and nuclear DNA
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Beverly Y, Mok, Anna V, Kotrys, Aditya, Raguram, Tony P, Huang, Vamsi K, Mootha, and David R, Liu
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Gene Editing ,Cytidine Deaminase ,Humans ,CRISPR-Cas Systems ,DNA, Mitochondrial ,Mitochondria - Abstract
The all-protein cytosine base editor DdCBE uses TALE proteins and a double-stranded DNA-specific cytidine deaminase (DddA) to mediate targeted C•G-to-T•A editing. To improve editing efficiency and overcome the strict TC sequence-context constraint of DddA, we used phage-assisted non-continuous and continuous evolution to evolve DddA variants with improved activity and expanded targeting scope. Compared to canonical DdCBEs, base editors with evolved DddA6 improved mitochondrial DNA (mtDNA) editing efficiencies at TC by 3.3-fold on average. DdCBEs containing evolved DddA11 offered a broadened HC (H = A, C or T) sequence compatibility for both mitochondrial and nuclear base editing, increasing average editing efficiencies at AC and CC targets from less than 10% for canonical DdCBE to 15-30% and up to 50% in cell populations sorted to express both halves of DdCBE. We used these evolved DdCBEs to efficiently install disease-associated mtDNA mutations in human cells at non-TC target sites. DddA6 and DddA11 substantially increase the effectiveness and applicability of all-protein base editing.
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- 2021
15. Deep learning methods improve polygenic risk analysis and prediction for Alzheimer’s disease
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Vincent Mok, Ronnie M. N. Lo, Shuangshuang Ma, Maryam Shoai, Amy K.Y. Fu, Jiahang Chen, Xiaopu Zhou, Qihao Guo, Huan Zhong, Estella P.S. Tong, Alzheimer’s Disease Neuroimaging Initiative, Kin Y. Mok, Yu Chen, Timothy Kwok, Tao Ye, John Hardy, Lei Chen, Yuewen Chen, Han Cao, Yulin Zhang, Fanny C.F. Ip, Nancy Y. Ip, and Yuanbing Jiang
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Gerontology ,business.industry ,Deep learning ,Medicine ,Polygenic risk score ,Artificial intelligence ,Disease ,business - Abstract
Recent advances in genetic sequencing have enabled comprehensive genetic analyses of human diseases, resulting in the identification of numerous genetic risk factors for heritable disorders including Alzheimer’s disease (AD). Such analyses enable AD risk prediction well before disease onset, which is critical for early interventions. However, current analytical approaches have limited ability to accurately estimate the risk effects of genetic variants owing to epistatic effects, which have been overlooked in most previous studies, resulting in unsatisfactory disease risk prediction. Herein, we modeled AD polygenic risk using deep learning methods, which outperformed existing models (i.e., weighted polygenic risk score and lasso models) for classifying disease risk. Moreover, by examining the associations between the outcomes from deep learning methods and multi-omics data obtained from our in-house Chinese AD cohorts, we identified the pathways that are potentially regulated by AD polygenic risk, including immune-associated signaling pathways. Thus, our results demonstrate the utility of deep learning methods for modeling the genetic risks of human diseases, which can facilitate both disease risk classification and the study of disease mechanisms.
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- 2021
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16. The parasite-derived peptide FhHDM-1 activates the PI3K/Akt pathway to prevent cytokine-induced apoptosis of β-cells
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Inah, Camaya, Tsz Y, Mok, Maria, Lund, Joyce, To, Nady, Braidy, Mark W, Robinson, Jerran, Santos, Bronwyn, O'Brien, and Sheila, Donnelly
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Male ,Phosphatidylinositol 3-Kinases ,Mice, Inbred NOD ,Insulin-Secreting Cells ,Animals ,Cytokines ,Humans ,Apoptosis ,Fasciola hepatica ,Peptides ,Proto-Oncogene Proteins c-akt ,Cells, Cultured ,Signal Transduction - Abstract
Type 1 diabetes (T1D) is an autoimmune disease characterised by the destruction of the insulin-producing beta (β)-cells within the pancreatic islets. We have previously identified a novel parasite-derived molecule, termed Fasciola hepatica helminth defence molecule 1 (FhHDM-1), that prevents T1D development in non-obese diabetic (NOD) mice. In this study, proteomic analyses of pancreas tissue from NOD mice suggested that FhHDM-1 activated the PI3K/Akt signalling pathway, which is associated with β-cell metabolism, survival and proliferation. Consistent with this finding, FhHDM-1 preserved β-cell mass in NOD mice. Examination of the biodistribution of FhHDM-1 after intraperitoneal administration in NOD mice revealed that the parasite peptide localised to the pancreas, suggesting that it exerted a direct effect on the survival/function of β-cells. This was confirmed in vitro, as the interaction of FhHDM-1 with the NOD-derived β-cell line, NIT-1, resulted in increased levels of phosphorylated Akt, increased NADH and NADPH and reduced activity of the NAD-dependent DNA nick sensor, poly(ADP-ribose) polymerase (PARP-1). As a consequence, β-cell survival was enhanced and apoptosis was prevented in the presence of the pro-inflammatory cytokines that destroy β-cells during T1D pathogenesis. Similarly, FhHDM-1 protected primary human islets from cytokine-induced apoptosis. Importantly, while FhHDM-1 promoted β-cell survival, it did not induce proliferation. Collectively, these data indicate that FhHDM-1 has significant therapeutic applications to promote β-cell survival, which is required for T1D and T2D prevention and islet transplantation. KEY MESSAGES: FhHDM-1 preserves β-cell mass in NOD mice and prevents the development of T1D. FhHDM-1 enhances phosphorylation of Akt in mouse β-cell lines. FhHDM-1 increases levels of NADH/NADPH in mouse β-cell lines in vitro. FhHDM-1 prevents cytokine-induced cell death of mouse β-cell lines and primary human β-cells in vitro via activation of the PI3K/Akt pathway.
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- 2021
17. Relationship between sodium removal, hydration and outcomes in peritoneal dialysis patients
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Natalie M.-Y. Mok, Stanley Fan, Nicholas Fan, and Hazel Finney
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Adult ,Male ,medicine.medical_specialty ,Sodium Clearance ,Sodium ,medicine.medical_treatment ,Urology ,Water-Electrolyte Imbalance ,Peritonitis ,chemistry.chemical_element ,Peritoneal dialysis ,Cohort Studies ,Risk Factors ,medicine ,Humans ,Risk factor ,Aged ,Retrospective Studies ,Dialysis adequacy ,business.industry ,General Medicine ,Middle Aged ,medicine.disease ,Transplantation ,Treatment Outcome ,chemistry ,Nephrology ,Sarcopenia ,Kidney Failure, Chronic ,Female ,business ,Peritoneal Dialysis - Abstract
Background Fluid overload (FO) in peritoneal dialysis (PD) patients is associated with mortality. We explore if low daily sodium removal is an independent risk factor for mortality. We examined severely FO PD patients established for >1yr in expectation that PD prescription would have been optimised for solute clearance and ultrafiltration. We also wish to determine the relationship between kt/v and sodium removal. Methods Retrospective analysis of 231 PD patients with FO ≥2.0L and compared with 218 PD patients who were euvolaemic throughout their PD treatment. Patients were followed up until death censored for transplantation. Results Mean daily sodium removal in overhydrated patients was only 75mmoles (=1.7g). CAPD usage was more common in patients with highest sodium removal. Achievement of UK guidelines for solute clearance and daily fluid removal were not independent predictors of mortality. Markers of sarcopenia (low serum albumin and high CRP) were associated with increased mortality, but these parameters were not independent predictors in a model that included functional assessment (Karnofsky Score). Daily sodium removal was not predictive of mortality but imprecision of clinically used sodium assay should be noted. Correlation between Na and kt/v is statistically significant but R2 was weak at 0.07. Conclusions Whilst diabetic males were more likely to become overhydrated, these factors did not increase mortality further. Traditional targets of "dialysis adequacy" did not predict survival. Kt/v is not a good indicator of sodium removal which can be surprisingly low. Measuring sodium clearance may help clinicians optimise PD modality (CAPD vs APD). This article is protected by copyright. All rights reserved.
- Published
- 2021
18. The East Asian Parkinson Disease Genomics Consortium
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Kin Y. Mok, Tatsushi Toda, Chunyu Li, Anh Tuan Nguyen, Bei-Sha Tang, Huong Thi Thanh Nguyen, Sulev Kõks, Wing Chi Fong, Yih-Ru Wu, Nor Azian Abdul Murad, Huifeng Shang, Wael Mohamed, Wataru Satake, Germaine Hiu Fai Chan, John Hardy, Amy Ky Fu, Chin-Hsein Lin, Phillip Chan, Lewis Singleton, Xiaopu Zhou, Yuewen Chen, Mong-Hsun Tsai, Kotaro Ogaki, Thi Thanh Huyen Vu, Shahrul Azmin, Nobutaka Hattori, Kin Y Mok, Tao Ye, Renpei Sengoku, Ji-Feng Guo, Seong-Min Choi, Ruey-Meei Wu, Siti Aishah Sulaiman, Manabu Funayama, Cornelis Blauwendraat, Hidetomo Murakami, Yu Chen, Norlinah Mohamed Ibrahim, Yun Joong Kim, Yu-An Su, Hsiu-Chuan Wu, Nancy Y Ip, Fanny Cf Ip, Andrew B. Singleton, Mike A. Nalls, Han Cao, Abigail Pfaff, Nelson Yuk-Fai Cheung, Kenya Nishioka, Tomotaka Shiraishi, Seok Jong Chung, and Siti Hajar Md Desa
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Asian People ,Asia, Eastern ,Humans ,Parkinson Disease ,Genomics ,East Asia ,Neurology (clinical) ,Disease ,Biology ,Socioeconomics - Published
- 2021
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19. Genetic determinants of survival in progressive supranuclear palsy: a genome-wide association study
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Clifton L. Dalgard, Ruth Chia, Claire Troakes, Steve M. Gentleman, Yaroslau Compta, John C. van Swieten, Owen A. Ross, Ellen Gelpi, Michele T.M. Hu, Alistair Church, James B. Rowe, Alex Rajput, Sonja W. Scholz, Raffaele Ferrari, Liana S. Rosenthal, Regina H. Reynolds, Sigrun Roeber, Thomas T. Warner, Jinhui Ding, Leslie W. Ferguson, Cornelis Blauwendraat, Edwin Jabbari, Kieren Allinson, Safa Al-Sarraj, P. Nigel Leigh, Thomas Arzberger, J. Raphael Gibbs, Gesine Respondek, Huw R. Morris, Rebecca R. Valentino, Maryam Shoai, Christopher Morris, Kin Y. Mok, Christopher Kobylecki, Mark R. Cookson, Adam L. Boxer, Janice L. Holton, Zane Jaunmuktane, Alexander Gerhard, Armin Giese, Coralie Viollet, David J. Burn, Dennis W. Dickson, Bryan J. Traynor, Nicola Pavese, Shunsuke Koga, Olga Pletnikova, Günter U. Höglinger, John Hardy, David Murphy, Tamas Revesz, Alexander Pantelyat, Andrew J. Lees, Juan C. Troncoso, Mina Ryten, Manuela Tan, Rowe, James [0000-0001-7216-8679], Apollo - University of Cambridge Repository, and Parkinson's UK
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0301 basic medicine ,Oncology ,Male ,Linkage disequilibrium ,genetics [RNA, Long Noncoding] ,Genome-wide association study ,Kaplan-Meier Estimate ,Linkage Disequilibrium ,0302 clinical medicine ,Databases, Genetic ,Age of Onset ,genetics [Supranuclear Palsy, Progressive] ,Hazard ratio ,Middle Aged ,genetics [Chromosomes, Human, Pair 12] ,genetics [Polymorphism, Single Nucleotide] ,Female ,RNA, Long Noncoding ,Supranuclear Palsy, Progressive ,Adult ,medicine.medical_specialty ,Single-nucleotide polymorphism ,PSP Genetics Group ,mortality [Supranuclear Palsy, Progressive] ,Leucine-Rich Repeat Serine-Threonine Protein Kinase-2 ,Polymorphism, Single Nucleotide ,White People ,03 medical and health sciences ,Internal medicine ,medicine ,Humans ,Genetic Predisposition to Disease ,ddc:610 ,Survival analysis ,Aged ,Neurology & Neurosurgery ,Chromosomes, Human, Pair 12 ,Proportional hazards model ,business.industry ,Genetic Variation ,1103 Clinical Sciences ,Survival Analysis ,eye diseases ,030104 developmental biology ,Expression quantitative trait loci ,genetics [Leucine-Rich Repeat Serine-Threonine Protein Kinase-2] ,Neurology (clinical) ,Age of onset ,1109 Neurosciences ,business ,030217 neurology & neurosurgery ,Genome-Wide Association Study - Abstract
Summary Background The genetic basis of variation in the progression of primary tauopathies has not been determined. We aimed to identify genetic determinants of survival in progressive supranuclear palsy (PSP). Methods In stage one of this two stage genome-wide association study (GWAS), we included individuals with PSP, diagnosed according to pathological and clinical criteria, from two separate cohorts: the 2011 PSP GWAS cohort, from brain banks based at the Mayo Clinic (Jacksonville, FL, USA) and in Munich (Germany), and the University College London PSP cohort, from brain banks and the PROSPECT study, a UK-wide longitudinal study of patients with atypical parkinsonian syndromes. Individuals were included if they had clinical data available on sex, age at motor symptom onset, disease duration (from motor symptom onset to death or to the date of censoring, Dec 1, 2019, if individuals were alive), and PSP phenotype (with reference to the 2017 Movement Disorder Society criteria). Genotype data were used to do a survival GWAS using a Cox proportional hazards model. In stage two, data from additional individuals from the Mayo Clinic brain bank, which were obtained after the 2011 PSP GWAS, were used for a pooled analysis. We assessed the expression quantitative trait loci (eQTL) profile of variants that passed genome-wide significance in our GWAS using the Functional Mapping and Annotation of GWAS platform, and did colocalisation analyses using the eQTLGen and PsychENCODE datasets. Findings Data were collected and analysed between Aug 1, 2016, and Feb 1, 2020. Data were available for 1001 individuals of white European ancestry with PSP in stage one. We found a genome-wide significant association with survival at chromosome 12 (lead single nucleotide polymorphism rs2242367, p=7·5 × 10−10, hazard ratio 1·42 [95% CI 1·22–1·67]). rs2242367 was associated with survival in the individuals added in stage two (n=238; p=0·049, 1·22 [1·00–1·48]) and in the pooled analysis of both stages (n=1239; p=1·3 × 10−10, 1·37 [1·25–1·51]). An eQTL database screen revealed that rs2242367 is associated with increased expression of LRRK2 and two long intergenic non-coding RNAs (lncRNAs), LINC02555 and AC079630.4, in whole blood. Although we did not detect a colocalisation signal for LRRK2, analysis of the PSP survival signal and eQTLs for LINC02555 in the eQTLGen blood dataset revealed a posterior probability of hypothesis 4 of 0·77, suggesting colocalisation due to a single shared causal variant. Interpretation Genetic variation at the LRRK2 locus was associated with survival in PSP. The mechanism of this association might be through a lncRNA-regulated effect on LRRK2 expression because LINC02555 has previously been shown to regulate LRRK2 expression. LRRK2 has been associated with sporadic and familial forms of Parkinson's disease, and our finding suggests a genetic overlap with PSP. Further functional studies will be important to assess the potential of LRRK2 modulation as a disease-modifying therapy for PSP and related tauopathies. Funding PSP Association, CBD Solutions, Medical Research Council (UK).
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- 2021
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20. SORL1 ‐variant carriers in ADES‐ADSP: A higher level of variant pathogenicity associates with earlier age at onset of Alzheimer's disease
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Rebecca Sims, Detelina Grozeva, John Hardy, Jordi Clarimón, Cornelia M. van Duijn, Gaël Nicolas, Kin Y. Mok, Najaf Amin, Maryam Shoai, Benjamin Grenier-Boley, Jeroen van Rooij, Philippe Amouyel, Oriol Dols-Icardo, Holger Hummerich, Shahzad Ahmad, Penny Norsworthy, Henne Holstege, Olivier Quenez, Amit Kawalia, Marc Hulsman, Camille Charbonnier, Alfredo Ramirez, Julie Williams, Simon Mead, Céline Bellenguez, John C. van Swieten, Jean-Charles Lambert, and Wiesje M. van der Flier
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Genetics ,Psychiatry and Mental health ,Cellular and Molecular Neuroscience ,Developmental Neuroscience ,Epidemiology ,Health Policy ,SORL1 ,Neurology (clinical) ,Disease ,Geriatrics and Gerontology ,Biology ,Pathogenicity - Published
- 2020
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21. Exome sequencing identifies three novel AD‐associated genes
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Jean-Charles Lambert, Kin Y. Mok, Olivier Quenez, Cornelia M. van Duijn, Wiesje M. van der Flier, Alfredo Ramirez, Philippe Amouyel, Gaël Nicolas, Amit Kawalia, Shahzad Ahmad, Simon Mead, Marc Hulsman, Detelina Grozeva, Penny Norsworthy, Holger Hummerich, John C. van Swieten, Henne Holstege, Rebecca Sims, Julie Williams, Céline Bellenguez, Jordi Clarimón, Najaf Amin, Maryam Shoai, Jeroen van Rooij, Oriol Dols-Icardo, Camille Charbonnier, Benjamin Grenier-Boley, and John Hardy
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Genetics ,Psychiatry and Mental health ,Cellular and Molecular Neuroscience ,Developmental Neuroscience ,Epidemiology ,Health Policy ,Neurology (clinical) ,Disease ,Geriatrics and Gerontology ,Biology ,Gene ,Exome sequencing - Published
- 2020
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22. Evaluation of genetic risk for Alzheimer’s disease in the Hong Kong Chinese population
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Shuangshuang Ma, Nancy Y. Ip, Xiaopu Zhou, Yulin Zhang, Fanny C.F. Ip, Kin Y. Mok, Estella P.S. Tong, Timothy Kwok, Saijuan Liu, Vincent Mok, Yu Chen, Nicole C. H. Lai, Yuewen Chen, Yuen Tung Li, John Hardy, and Amy K.Y. Fu
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Gerontology ,Chinese population ,Epidemiology ,business.industry ,Health Policy ,Disease ,Psychiatry and Mental health ,Cellular and Molecular Neuroscience ,Developmental Neuroscience ,Medicine ,Neurology (clinical) ,Geriatrics and Gerontology ,Genetic risk ,business - Published
- 2020
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23. Lifetime cost-effectiveness analysis of first-line dialysis modalities for patients with end-stage renal disease under peritoneal dialysis first policy
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Wai Kei Lo, Maggie M Y Mok, Samuel K. S. Fung, Tak Mao Chan, Irene Kong, Sing Leung Lui, Cindy L. K. Lam, Julie Y. Chen, Yuk Lun Cheng, and Carlos K. H. Wong
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Nephrology ,medicine.medical_specialty ,Outpatient Clinics, Hospital ,Cost effectiveness ,Cost-Benefit Analysis ,medicine.medical_treatment ,First line ,Hemodialysis, Home ,Economic burden ,lcsh:RC870-923 ,End stage renal disease ,Peritoneal dialysis ,End-stage renal disease ,Internal medicine ,medicine ,Nocturnal home haemodialysis ,Humans ,health care economics and organizations ,Dialysis ,Modalities ,business.industry ,Health Care Costs ,Cost-effectiveness analysis ,Middle Aged ,lcsh:Diseases of the genitourinary system. Urology ,Markov Chains ,Emergency medicine ,Kidney Failure, Chronic ,Cost-effectiveness ,Quality-Adjusted Life Years ,business ,Peritoneal Dialysis ,Peritoneal dialysis first ,Research Article - Abstract
Background This study aimed to determine the lifetime cost-effectiveness of first-line dialysis modalities for end-stage renal disease (ESRD) patients under the “Peritoneal Dialysis First” policy. Methods Lifetime cost-effectiveness analyses from both healthcare provider and societal perspectives were performed using Markov modelling by simulating at age 60. Empirical data on costs and health utility scores collected from our studies were combined with published data on health state transitions and survival data to estimate the lifetime cost, quality-adjusted life-years (QALYs) and cost-effectiveness of three competing dialysis modalities: peritoneal dialysis (PD), hospital-based haemodialysis (HD) and nocturnal home HD. Results For cost-effectiveness analysis over a lifetime horizon from the perspective of healthcare provider, hospital-based HD group (lifetime cost USD$142,389; 6.58 QALYs) was dominated by the PD group (USD$76,915; 7.13 QALYs). Home-based HD had the highest effectiveness (8.37 QALYs) but with higher cost (USD$97,917) than the PD group. The incremental cost-effectiveness ratio (ICER) was USD$16,934 per QALY gained for home-based HD over PD. From the societal perspective, the results were similar and the ICER was USD$1195 per QALY gained for home-based HD over PD. Both ICERs fell within the acceptable thresholds. Changes in model parameters via sensitivity analyses had a minimal impact on ICER values. Conclusions This study assessed the cost-effectiveness of dialysis modalities and service delivery models for ESRD patients under “Peritoneal Dialysis First” policy. For both healthcare provider and societal perspectives, PD as first-line dialysis modality was cost-saving relative to hospital-based HD, supporting the existing PD First or favoured policy. When compared with PD, Nocturnal home Home-based HD was considered a cost-effective first-line dialysis modality for ESRD patients.
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- 2020
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24. Dystonia genes functionally converge in specific neurons and share neurobiology with psychiatric disorders
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Regina H. Reynolds, Kerri J. Kinghorn, Lea R'Bibo, Alastair J. Noyce, Henry Houlden, Elena Zholdybayeva, Niccolo E. Mencacci, Patrick A. Lewis, Claudia Manzoni, Nazira Zharkinbekova, Daniah Trabzuni, Nicholas W. Wood, Sebastian Guelfi, John Hardy, Valentina Escott-Price, Rita Guerreiro, Ruth C. Lovering, Chris-Ann Mackenzie, Juan A. Botía, Álvaro Sánchez-Ferrer, John P. Quinn, Viola Volpato, Rauan Kaiyrzhanov, Peter Holmans, Caleb Webber, Huw R. Morris, Sonia Garcia Ruiz, Kirsten Harvey, Nigel Williams, Thomas Foltynie, Colin Smith, Viorica Chelban, Ben Middlehurst, Kin Y. Mok, Karishma D’Sa, Adaikalavan Ramasamy, Chingiz Shashakin, Kailash P. Bhatia, Helene Plun-Favreau, Jana Vandrovcova, Mina Ryten, Manuela Tan, Mie Rizig, Kimberley Billingsley, Demis A. Kia, Akbota Aitkulova, Paola Forabosco, Jose Bras, and Michael E. Weale
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0301 basic medicine ,medicine.medical_specialty ,Substantia nigra ,Neurological disorder ,Biology ,Medium spiny neuron ,03 medical and health sciences ,0302 clinical medicine ,Neurobiology ,otorhinolaryngologic diseases ,medicine ,synaptic transmission ,Humans ,Gene Regulatory Networks ,Psychiatry ,network analysis ,transcriptomic analysis ,Dystonia ,Neurons ,AcademicSubjects/SCI01870 ,Putamen ,Mental Disorders ,Original Articles ,Human brain ,medicine.disease ,nervous system diseases ,030104 developmental biology ,medicine.anatomical_structure ,Neurology ,Schizophrenia ,Dystonic Disorders ,Major depressive disorder ,AcademicSubjects/MED00310 ,Neurology (clinical) ,medium-spiny neurons ,Erratum ,Neuroscience ,030217 neurology & neurosurgery - Abstract
Dystonia is a neurological disorder characterized by sustained or intermittent muscle contractions causing abnormal movements and postures, often occurring in absence of any structural brain abnormality. Psychiatric comorbidities, including anxiety, depression, obsessive-compulsive disorder and schizophrenia, are frequent in patients with dystonia. While mutations in a fast-growing number of genes have been linked to Mendelian forms of dystonia, the cellular, anatomical, and molecular basis remains unknown for most genetic forms of dystonia, as does its genetic and biological relationship to neuropsychiatric disorders. Here we applied an unbiased systems-biology approach to explore the cellular specificity of all currently known dystonia-associated genes, predict their functional relationships, and test whether dystonia and neuropsychiatric disorders share a genetic relationship. To determine the cellular specificity of dystonia-associated genes in the brain, single-nuclear transcriptomic data derived from mouse brain was used together with expression-weighted cell-type enrichment. To identify functional relationships among dystonia-associated genes, we determined the enrichment of these genes in co-expression networks constructed from 10 human brain regions. Stratified linkage-disequilibrium score regression was used to test whether co-expression modules enriched for dystonia-associated genes significantly contribute to the heritability of anxiety, major depressive disorder, obsessive-compulsive disorder, schizophrenia, and Parkinson’s disease. Dystonia-associated genes were significantly enriched in adult nigral dopaminergic neurons and striatal medium spiny neurons. Furthermore, 4 of 220 gene co-expression modules tested were significantly enriched for the dystonia-associated genes. The identified modules were derived from the substantia nigra, putamen, frontal cortex, and white matter, and were all significantly enriched for genes associated with synaptic function. Finally, we demonstrate significant enrichments of the heritability of major depressive disorder, obsessive-compulsive disorder and schizophrenia within the putamen, frontal cortex and white matter modules, and nominal enrichment of the heritability of Parkinson’s disease within the substantia nigra module. In conclusion, multiple dystonia-associated genes interact and contribute to pathogenesis likely through dysregulation of synaptic signalling in striatal medium spiny neurons, adult nigral dopaminergic neurons and frontal cortical neurons. Furthermore, the enrichment of the heritability of psychiatric disorders in the co-expression modules enriched for dystonia-associated genes indicates that psychiatric symptoms associated with dystonia are likely to be intrinsic to its pathophysiology., See Busch and Klein (doi:10.1093/brain/awaa253) for a scientific commentary on this article. Mencacci et al. show that multiple dystonia genes are functionally related and likely contribute to modulation of synaptic signalling in striatal, dopaminergic and frontal cortical neurons. They also demonstrate a genetic relationship between dystonia and psychiatric disorders including depression, OCD and schizophrenia.
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- 2020
25. Fulminant corticobasal degeneration: a distinct variant with predominant neuronal tau aggregates
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Lea R'Bibo, John C. Hedreen, Matthew Ellis, Gabor G. Kovacs, Kieren Allinson, Sebastian Brandner, Jean Paul Vonsattel, John Hardy, Thomas T. Warner, Eniko Veronika Kovari, Safa Al-Sarraj, David G. Mann, Glenda M. Halliday, Edwin Jabbari, Tamas Revesz, Johannes Attems, Helen Ling, Ellen Gelpi, James W. Ironside, Seth Love, Teisha Bradshaw, Roberto Simone, Rohan de Silva, Karen Davey, Núria Setó-Salvia, Kin Y. Mok, Daniela Hansen, Selina Wray, Janice L. Holton, Zane Jaunmuktane, Huw R. Morris, Ling, Helen [0000-0003-1532-3526], Revesz, Tamas [0000-0003-2501-0259], and Apollo - University of Cambridge Repository
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Male ,Neurofibrillary tangles ,Pathology ,medicine.medical_specialty ,Fulminant ,tau Proteins ,Disease ,Asymptomatic ,digestive system ,Pathology and Forensic Medicine ,Progressive supranuclear palsy ,ddc:616.89 ,Cellular and Molecular Neuroscience ,Basal Ganglia Diseases ,Humans ,Medicine ,Corticobasal degeneration ,Cognitive decline ,Pathological ,Aged ,Aged, 80 and over ,Cerebral Cortex ,Original Paper ,business.industry ,Astrocytic plaques ,Neurodegenerative Diseases ,Middle Aged ,medicine.disease ,digestive system diseases ,surgical procedures, operative ,Concomitant ,Disease Progression ,Female ,Neurology (clinical) ,medicine.symptom ,Tau ,business - Abstract
Corticobasal degeneration typically progresses gradually over 5–7 years from onset till death. Fulminant corticobasal degeneration cases with a rapidly progressive course were rarely reported (RP-CBD). This study aimed to investigate their neuropathological characteristics. Of the 124 autopsy-confirmed corticobasal degeneration cases collected from 14 centres, we identified 6 RP-CBD cases (4.8%) who died of advanced disease within 3 years of onset. These RP-CBD cases had different clinical phenotypes including rapid global cognitive decline (N = 2), corticobasal syndrome (N = 2) and Richardson’s syndrome (N = 2). We also studied four corticobasal degeneration cases with an average disease duration of 3 years or less, who died of another unrelated illness (Intermediate-CBD). Finally, we selected 12 age-matched corticobasal degeneration cases out of a cohort of 110, who had a typical gradually progressive course and reached advanced clinical stage (End-stage-CBD). Quantitative analysis showed high overall tau burden (p = 0.2) and severe nigral cell loss (p = 0.47) in both the RP-CBD and End-stage-CBD groups consistent with advanced pathological changes, while the Intermediate-CBD group (mean disease duration = 3 years) had milder changes than End-stage-CBD (p p p = 0.02). In contrast to the predominance of astrocytic plaques we previously reported in preclinical asymptomatic corticobasal degeneration cases, neuronal tau aggregates predominated in RP-CBD exceeding those in Intermediate-CBD (anterior frontal cortex: p p = 0.001) and End-stage-CBD (anterior frontal cortex: p = 0.03, caudate: p = 0.01) as demonstrated by its higher neuronal-to-astrocytic plaque ratios in both anterior frontal cortex and caudate. We did not identify any difference in age at onset, any pathogenic tau mutation or concomitant pathologies that could have contributed to the rapid progression of these RP-CBD cases. Mild TDP-43 pathology was observed in three RP-CBD cases. All RP-CBD cases were men. The MAPT H2 haplotype, known to be protective, was identified in one RP-CBD case (17%) and 8 of the matched End-stage-CBD cases (67%). We conclude that RP-CBD is a distinct aggressive variant of corticobasal degeneration with characteristic neuropathological substrates resulting in a fulminant disease process as evident both clinically and pathologically. Biological factors such as genetic modifiers likely play a pivotal role in the RP-CBD variant and should be the subject of future research.
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- 2020
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26. Longterm Data on Sirolimus Treatment in Patients with Lupus Nephritis
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Maggie M Y Mok, Lorraine P Y Kwan, Maggie K.M. Ma, Colin S.O. Tang, Tak Mao Chan, Desmond Y H Yap, and Gary C.W. Chan
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Adult ,Male ,0301 basic medicine ,medicine.medical_specialty ,Prednisolone ,Immunology ,Lupus nephritis ,Urology ,Renal function ,03 medical and health sciences ,0302 clinical medicine ,Rheumatology ,Humans ,Immunology and Allergy ,Medicine ,Retrospective Studies ,Sirolimus ,030203 arthritis & rheumatology ,Proteinuria ,business.industry ,Standard treatment ,Middle Aged ,medicine.disease ,Lupus Nephritis ,Treatment Outcome ,030104 developmental biology ,Drug Therapy, Combination ,Female ,medicine.symptom ,business ,Stage 4 chronic kidney disease ,Nephritis ,Immunosuppressive Agents ,medicine.drug - Abstract
Objective.To expand the limited longterm data on sirolimus treatment in patients with lupus nephritis (LN). Our pilot short-term data suggested efficacy of sirolimus treatment in these patients.Methods.We retrospectively reviewed 16 class III/IV/V patients with LN who have received prednisolone (PSL) and sirolimus either as initial or maintenance treatment.Results.Sixteen patients received sirolimus treatment (9 because of intolerance to standard immunosuppressants and 7 because of a history of malignancy) for 45.3 ± 36.5 months. In 5 patients, sirolimus and PSL were given as induction for active nephritis, and they showed improvements in proteinuria (2.8 ± 1.9 g/day at baseline, 0.1 ± 0.1 g/day after 36 mos, p = 0.011), anti-dsDNA (107.7 ± 91.9 IU/ml and 37.0 ± 55.4 IU/ml, respectively, p = 0.178), and C3 (54.8 ± 26.1 mg/dl and 86.3 ± 18.6 mg/dl, respectively, p = 0.081). Eleven patients received sirolimus and low-dose PSL as longterm maintenance, and they showed continued improvement in C3 (90.4 ± 18.1 mg/dl and 117.7 ± 25.1 mg/dl at commencement and after 36 mos, respectively, p = 0.025), stable renal function (estimated glomerular filtration rate 58.6 ± 25.8 ml/min and 63.0 ± 29.6 ml/min, respectively, p = 0.239), and proteinuria (0.8 ± 0.7 g/day and 0.7 ± 0.7 g/day respectively, p = 0.252). Renal flare occurred in 1 patient, and another patient who had stage 4 chronic kidney disease when sirolimus was started developed endstage renal failure after 27 months. Sirolimus was discontinued in 5 patients, in 4 cases related to drug side effects. Deterioration of dyslipidemia occurred in 4 patients, but was adequately controlled with statin therapy.Conclusion.The preliminary evidence suggests that sirolimus may serve as an alternative treatment for patients with LN who do not tolerate standard treatment or who had a history of malignancy, and it has an acceptable longterm safety profile.
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- 2018
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27. Smile attractiveness related to buccal corridor space in 3 different facial types: A perception of 3 ethnic groups of Malaysians
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Jing Y. Tioh, Reei Y. Mok, Yih Y. Oh, Kai J. Yew, Pravinkumar G. Patil, and Smita Nimbalkar
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Adult ,Male ,Attractiveness ,Visual perception ,Adolescent ,media_common.quotation_subject ,Ethnic group ,Ethnic populations ,Esthetics, Dental ,Space (commercial competition) ,Smiling ,Statistics, Nonparametric ,Young Adult ,03 medical and health sciences ,0302 clinical medicine ,Perception ,parasitic diseases ,Ethnicity ,Humans ,030212 general & internal medicine ,Normal face ,media_common ,Observer Variation ,Orthodontics ,030206 dentistry ,Buccal administration ,Photography, Dental ,Face ,Visual Perception ,Female ,Oral Surgery ,Psychology - Abstract
Statement of problem Buccal corridor space and its variations greatly influence smile attractiveness. Facial types are different for different ethnic populations, and so is smile attractiveness. The subjective perception of smile attractiveness of different populations may vary in regard to different buccal corridor spaces and facial patterns. Purpose The purpose of this study was to determine esthetic perceptions of the Malaysian population regarding the width of buccal corridor spaces and their effect on smile esthetics in individuals with short, normal, and long faces. Material and methods The image of a smiling individual with a mesofacial face was modified to create 2 different facial types (brachyfacial and dolicofacial). Each face form was further modified into 5 different buccal corridors (2%, 10%, 15%, 22%, and 28%). The images were submitted to 3 different ethnic groups of evaluators (Chinese, Malay, Indian; 100 each), ranging between 17 and 21 years of age. A visual analog scale (50 mm in length) was used for assessment. The scores given to each image were compared with the Kruskal-Wallis test, and pairwise comparison was performed using the Mann-Whitney U test (α=.05). Results All 3 groups of evaluators could distinguish gradations of dark spaces in the buccal corridor at 2%, 10%, and 28%. Statistically significant differences were observed among 3 groups of evaluators in esthetic perception when pairwise comparisons were performed. A 15% buccal corridor was found to score esthetically equally within 3 face types by all 3 groups of evaluators. The Indian population was more critical in evaluation than the Chinese or Malay populations. In a pairwise comparison, more significant differences were found between long and short faces and the normal face; the normal face was compared with long and short faces separately. Conclusions The width of the buccal corridor space influences smile attractiveness in different facial types. A medium buccal corridor (15%) is the esthetic characteristic preferred by all groups of evaluators in short, normal, and long face types.
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- 2018
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28. Preemptive immunosuppressive treatment for asymptomatic serological reactivation may reduce renal flares in patients with lupus nephritis: a cohort study
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Maggie M Y Mok, Maggie K.M. Ma, Gary C.W. Chan, Desmond Y H Yap, Tak Mao Chan, and Lorraine P Y Kwan
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Adult ,Male ,medicine.medical_specialty ,Prednisolone ,medicine.medical_treatment ,030232 urology & nephrology ,Lupus nephritis ,Renal function ,030204 cardiovascular system & hematology ,Gastroenterology ,Asymptomatic ,03 medical and health sciences ,0302 clinical medicine ,Recurrence ,Internal medicine ,Azathioprine ,medicine ,Humans ,Survival rate ,Retrospective Studies ,Transplantation ,Kidney ,business.industry ,Hazard ratio ,Immunosuppression ,Mycophenolic Acid ,medicine.disease ,Lupus Nephritis ,Survival Rate ,Treatment Outcome ,medicine.anatomical_structure ,Nephrology ,Disease Progression ,Female ,Kidney Diseases ,medicine.symptom ,business ,Immunosuppressive Agents ,Glomerular Filtration Rate ,medicine.drug - Abstract
Background Serological activity may precede clinical flares of lupus nephritis (LN) but the management of asymptomatic serological reactivation (ASR) remains undefined. Methods We conducted a retrospective analysis of 138 episodes of ASR, which included 53 episodes in which immunosuppression was increased preemptively and 85 episodes in which treatment was unaltered. Preemptive immunosuppressive treatment comprised increasing the dose of prednisolone to ∼0.5 mg/kg/day, and in patients already on mycophenolate mofetil (MMF) or azathioprine (AZA), increasing the dose to 1.5 g/day and 100 mg/day, respectively. Results Thirty-four episodes of renal flare occurred during follow-up (88.8 ± 77.3 and 82.8 ± 89.7 months in the preemptive group and controls, respectively), following 5 (9.4%) of preemptively treated ASR and 27 (31.8%) of untreated ASR [hazard ratio 0.3 (confidence interval 0.1-0.7), P = 0.012]. Preemptive treatment was associated with superior survival free of renal relapse (99, 92 and 90% at 6, 12 and 24 month, respectively, compared with 94, 69 and 64% in controls; P = 0.011), whereas survival rate free of extrarenal relapse was similar in the two groups. Preemptively treated patients who did not develop renal flares showed better renal function preservation (estimated glomerular filtration rate slope +0.54 ± 0.43 mL/min/1.73 m2/year, compared with -2.11 ± 0.50 and -1.00 ± 0.33 mL/min/1.73 m2/year, respectively, in controls who did and did not develop subsequent renal flares; P = 0.001 and 0.012, respectively). Preemptive treatment was associated with an increased incidence of gastrointestinal side effects attributed to MMF (P = 0.031), whereas infection rate did not differ between the two groups. Conclusion A preemptive moderate increase of immunosuppression for ASR in LN patients may reduce renal flares and confer benefit to long-term renal function.
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- 2018
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29. Simulation of equilibrium and transport in advanced FRCS
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Calvin Lau, Elena Belova, Toshiki Tajima, Jaeyoung Park, Sean Dettrick, Bradley Scott Nicks, Ales Necas, Y. Mok, Sergei Galkin, Kateryna Yakymenko, Marco Onofri, Kevin Hubbard, Laura Galeotti, Wenhao Wang, Sergei Putvinski, Daniel C. Barnes, F. Ceccherini, Oleksandr Koshkarov, Sangeeta Gupta, Peter Yushmanov, L. C. Steinhauer, Xishuo Wei, and Zhihong Lin
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Nuclear and High Energy Physics ,Electron density ,education.field_of_study ,Tokamak ,Materials science ,Ambipolar diffusion ,Population ,Electron ,Plasma ,Condensed Matter Physics ,Computational physics ,law.invention ,Physics::Plasma Physics ,law ,Electric field ,Field-reversed configuration ,education - Abstract
The advanced beam-driven FRC is a Field Reversed Configuration (FRC) with the addition of neutral beam (NB) injection, electrode biasing, and magnetic expander divertors. The resulting configuration has novel features that make it necessary to revisit many key results in FRC theory. Three of these features include (i) a large energetic ion population, (ii) in-principle capability to adjust the electric field and rotation profiles, and (iii) a combination of magnetic and electrostatic confinement of electrons in the SOL. In some fueling scenarios the electron density profile may exhibit a significant peak outside of the separatrix. To explore these features a hybrid fluid/kinetic equilibrium model has been used to reconstruct typical experimental profiles of the C-2W experiment. Results indicate that the energetic ions provide at least 50% of the total plasma pressure. These equilibrium profiles have been used as initial conditions for global, cross-separatrix, turbulent transport simulations using the 3D electrostatic particle-in-cell code ANC. Electrostatic fluctuations were found to nonlinearly saturate at an amplitude which is an order magnitude lower than that observed previously. The tokamak turbulence code GTC code has also been extended to handle FRC physics in the new GTC-X version, which has been used to perform simulations of turbulent transport in the SOL relevant to electrode biasing. It is found that equilibrium × flow shear significantly decreases ion temperature gradient saturation amplitude and ion heat transport. Also in the SOL, a 1D2V continuum code has been developed and applied to parallel electron heat transport. Results show the formation of pre-sheath potential and reduction of parallel electron heat loss close to the ideal ambipolar limit, a result which has been validated by experimental diagnostics. These transport modifications caused by the three novel configuration features help to explain the remarkable plasma performance of the C-2W experiment.
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- 2021
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30. Overview of C-2W: high temperature, steady-state beam-driven field-reversed configuration plasmas
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H. Gota, M.W. Binderbauer, T. Tajima, A. Smirnov, S. Putvinski, M. Tuszewski, S.A. Dettrick, D.K. Gupta, S. Korepanov, R.M. Magee, J. Park, T. Roche, J.A. Romero, E. Trask, X. Yang, P. Yushmanov, K. Zhai, T. DeHaas, M.E. Griswold, S. Gupta, S. Abramov, A. Alexander, I. Allfrey, R. Andow, B. Barnett, M. Beall, N.G. Bolte, E. Bomgardner, A. Bondarenko, F. Ceccherini, L. Chao, R. Clary, A. Cooper, C. Deng, A. Dunaevsky, P. Feng, C. Finucane, D. Fluegge, L. Galeotti, S. Galkin, K. Galvin, E.M. Granstedt, K. Hubbard, I. Isakov, M. Kaur, J.S. Kinley, A. Korepanov, S. Krause, C.K. Lau, A. Lednev, H. Leinweber, J. Leuenberger, D. Lieurance, D. Madura, J. Margo, D. Marshall, R. Marshall, T. Matsumoto, V. Matvienko, M. Meekins, W. Melian, R. Mendoza, R. Michel, Y. Mok, M. Morehouse, R. Morris, L. Morton, M. Nations, A. Necas, S. Nicks, G. Nwoke, M. Onofri, A. Ottaviano, R. Page, E. Parke, K. Phung, G. Player, I. Sato, T.M. Schindler, J.H. Schroeder, D. Sheftman, A. Sibley, A. Siddiq, M. Signorelli, M. Slepchenkov, R.J. Smith, G. Snitchler, V. Sokolov, Y. Song, L.C. Steinhauer, V. Stylianou, J. Sweeney, J.B. Titus, A. Tkachev, M. Tobin, J. Ufnal, T. Valentine, A.D. Van Drie, J. Ward, C. Weixel, C. White, M. Wollenberg, S. Ziaei, null the TAE Team, L. Schmitz, Z. Lin, A.A. Ivanov, T. Asai, E.A. Baltz, M. Dikovsky, W.D. Heavlin, S. Geraedts, I. Langmore, P.C. Norgaard, R. Von Behren, T. Madams, A. Kast, and J.C. Platt
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Nuclear and High Energy Physics ,Materials science ,Steady state (electronics) ,Compact toroid ,Field-reversed configuration ,Aneutronic fusion ,Plasma ,Atomic physics ,Condensed Matter Physics ,Neutral beam injection ,Beam (structure) - Published
- 2021
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31. Longterm Data on Disease Flares in Patients with Proliferative Lupus Nephritis in Recent Years
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Maggie M Y Mok, Desmond Y H Yap, Maggie K.M. Ma, Colin S.O. Tang, Gary C.W. Chan, Lorraine P Y Kwan, and Tak Mao Chan
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Adult ,Male ,medicine.medical_specialty ,Prednisolone ,medicine.medical_treatment ,Immunology ,030232 urology & nephrology ,Lupus nephritis ,Azathioprine ,Disease ,Gastroenterology ,Disease-Free Survival ,Mycophenolic acid ,Young Adult ,03 medical and health sciences ,0302 clinical medicine ,Rheumatology ,Recurrence ,Internal medicine ,medicine ,Humans ,Immunology and Allergy ,In patient ,Survival rate ,030203 arthritis & rheumatology ,business.industry ,Remission Induction ,Immunosuppression ,Middle Aged ,Mycophenolic Acid ,medicine.disease ,Lupus Nephritis ,Surgery ,Treatment Outcome ,Disease Progression ,Female ,business ,Immunosuppressive Agents ,medicine.drug - Abstract
Objective.To examine the disease flare rate in lupus nephritis (LN), focusing on renal flares, and the factors associated with relapse risk in recent years.Methods.We analyzed data on 139 Chinese patients with class III/IV ± V LN diagnosed from January 1983 to December 2013. We also compared data before and after 1998, when maintenance immunosuppression was changed from azathioprine (AZA) to mycophenolic acid (MPA).Results.Over 112.5 ± 88.4 months, 135 episodes of renal flare occurred, giving a flare rate of 0.108 episodes per patient-year. The renal relapse-free survival rate was 96%, 90%, 86%, 80%, 69%, and 57% after 1, 2, 3, 4, 5, and 10 years, respectively, calculated from the start of induction treatment. Reduced risk of flare was associated with MPA maintenance (OR 0.314, 95% CI 0.099–0.994, p = 0.049), complete remission after induction immunosuppression (OR 0.329, 95% CI 0.133–0.810, p = 0.016), and diagnosis after 1998 (OR 0.305, 95% CI 0.133–0.700, p = 0.005). Relapse-free survival was significantly better in patients treated with prednisolone and MPA as maintenance immunosuppression (91% after 5 yrs and 83% after 10 yrs, respectively) compared with prednisolone and AZA (70% and 52%, respectively, p = 0.044). LN diagnosed in 1998–2013 showed 5-year and 10-year relapse-free survival rates of 93% and 86%, respectively, compared with 81% and 66%, respectively (p = 0.017) for LN that presented in 1983–1997.Conclusion.Our data show a relatively low flare rate for LN in the more recent era, attributed to effective induction of immunosuppression and MPA as maintenance treatment.
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- 2017
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32. 0627 Cognitive Perceptions Impact Short-Term CPAP Adherence in Asian Patients with Obstructive Sleep Apnea
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C A Png, J Chang, Y Mok, and J Liang
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Self-efficacy ,business.industry ,medicine.medical_treatment ,media_common.quotation_subject ,Gold standard ,Cognition ,medicine.disease ,respiratory tract diseases ,Risk perception ,Obstructive sleep apnea ,Physiology (medical) ,Perception ,Medicine ,Neurology (clinical) ,Continuous positive airway pressure ,business ,Patient education ,Clinical psychology ,media_common - Abstract
Introduction Adherence for the gold standard Continuous Positive Airway Pressure (CPAP) treatment for obstructive sleep apnea (OSA) is poor worldwide. Studies have explored factors impacting CPAP adherence but data is limited for Asian patients where cultural and social norms differ. This study aimed to examine the role of disease and treatment-related perceptions in short-term CPAP adherence among patients from a multi-ethnic Southeast Asian country. Methods 34 patients with newly diagnosed OSA were recruited from Changi General Hospital, a 1000-bed tertiary hospital in Singapore between September 2018 and February 2019. Psychological factors of self-efficacy, risk-perception and outcome expectancies were assessed with the Self-Efficacy Measure for Sleep Apnea (SEMSA) questionnaire. The SEMSA questionnaire has been previously validated for the evaluation of adherence-related cognitions. Patients were administered the SEMSA questionnaire before commencement of CPAP treatment and 1 month after. Results 73.5% (25/34) of the patients were male (82.4% Chinese, 11.8% Malays, 2.9% Indians, 2.9% others). Mean age was 43.3 ± 11.8 years, mean apnea hypopnea index (AHI) was 45.2 ± 29.6 events/hr and mean CPAP usage at one month was 3.6±2.0 hours. 47% were adherent to CPAP, defined as average device use > 4 hrs/day. Pre-treatment self-efficacy was significantly correlated with CPAP adherence (r = 0.498, P Conclusion Consistent with previous literature in Western population, our study demonstrated that patients’ cognitive perceptions of outcome expectancies and sense of self-efficacy have an impact on CPAP adherence in a Southeast Asian population. Strategies targeting these aspects would be important in designing patient education programs. Support
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- 2020
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33. Fibrillation and molecular characteristics are coherent with clinical and pathological features of 4-repeat tauopathy caused by MAPT variant G273R
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Marla Gearing, Laura B. Cantwell, Helen Ling, John Hardy, Stefan Thor, Per Hammarström, Lea R'Bibo, Allan I. Levey, Kin Y. Mok, Tamas Revesz, Samuel P.S. Svensson, Nicholas W. Wood, Alexander Sandberg, Beth A. Dombroski, Josefin Fernius, Gerard D. Schellenberg, and Sofie Nyström
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0301 basic medicine ,4-repeat tau ,Biology ,G273R ,medicine.disease_cause ,lcsh:RC321-571 ,Progressive supranuclear palsy ,03 medical and health sciences ,0302 clinical medicine ,Basal Ganglia Diseases ,Microtubule ,mental disorders ,MAPT ,Pathology ,medicine ,Corticobasal degeneration ,Animals ,lcsh:Neurosciences. Biological psychiatry. Neuropsychiatry ,Exome sequencing ,Medicinsk genetik ,Neurons ,Mutation ,Tauopathy ,CBD ,PSP ,Aggregation propensity ,Parkinsonism ,Brain ,medicine.disease ,In vitro ,Cell biology ,030104 developmental biology ,Neurology ,Tauopathies ,Drosophila ,Supranuclear Palsy, Progressive ,Medical Genetics ,Neuroglia ,030217 neurology & neurosurgery - Abstract
Microtubule Associated Protein Tau (MAPT) forms proteopathic aggregates in several diseases. The G273R tau mutation, located in the first repeat region, was found by exome sequencing in a patient who presented with dementia and parkinsonism. We herein return to pathological examination which demonstrated tau immunoreactivity in neurons and glia consistent of mixed progressive supranuclear palsy (PSP) and corticobasal degeneration (CBD) features. To rationalize the pathological findings, we used molecular biophysics to characterize the mutation in more detail in vitro and in Drosophila. The G273R mutation increases the aggregation propensity of 4-repeat (4R) tau and alters the tau binding affinity towards microtubules (MTs) and F-actin. Tau aggregates in PSP and CBD are predominantly 4R tau. Our data suggest that the G273R mutation induces a shift in pool of 4R tau by lower F-actin affinity, alters the conformation of MT bound 4R tau, while increasing chaperoning of 3R tau by binding stronger to F-actin. The mutation augmented fibrillation of 4R tau initiation in vitro and in glial cells in Drosophila and showed preferential seeding of 4R tau in vitro suggestively causing a late onset 4R tauopathy reminiscent of PSP and CBD. Funding Agencies|Karin & Sten Mortstedt CBD Solutions research grant [512385]; Swedish Research CouncilSwedish Research Council [201504521, 2019-04405]; Goran Gustafsson Foundation; Swedish Alzheimer Foundation; Swedish Brain foundation; Goizueta Alzheimers Disease Research Center at Emory University [NIH P50 AG025688]; UK Dementia Research Institute, from DRI Ltd.; UK Medical Research CouncilMedical Research Council UK (MRC); Alzheimers Society; Alzheimers Research UKAlzheimers Research UK (ARUK); Medical Research CouncilMedical Research Council UK (MRC) [MR/N026004/1]; Wellcome TrustWellcome Trust [202903/Z/16/Z]; Dolby Family Fund; National Institute for Health Research (NIHR) Biomedical Research Centre(BRC) at University College London Hospitals NHS Foundation TrustNational Institute for Health Research (NIHR); University College London; Michael J Fox Foundation; Michael J Fox Foundation.
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- 2019
34. Reply to 'Down Syndrome Cognitive Marker's Significance in Alzheimer's Disease and Dementia Management'
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Andre Strydom, Sarah Hamburg, Kin Y. Mok, Rosalyn Hithersay, Carla M. Startin, Tamara Al-Janabi, and John Hardy
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medicine.medical_specialty ,Down syndrome ,Epidemiology ,business.industry ,Health Policy ,MEDLINE ,Cognition ,Disease ,Neuropsychological Tests ,medicine.disease ,Psychiatry and Mental health ,Cellular and Molecular Neuroscience ,Developmental Neuroscience ,Alzheimer Disease ,medicine ,Dementia ,Humans ,Neurology (clinical) ,Geriatrics and Gerontology ,Alzheimer's disease ,Down Syndrome ,Psychiatry ,business ,Biomarkers - Published
- 2019
35. C9orf72 intermediate repeats are associated with corticobasal degeneration, increased C9orf72 expression and disruption of autophagy
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Wan Yun Ho, Claire Troakes, Edward B. Lee, Hans A. Kretzschmar, Charles L. White, Virginia M.-Y. Lee, Helen Ling, Christopher P. Cali, Catriona McLean, Jean Paul Vonsattel, Bernardino Ghetti, Juan C. Troncoso, Gerard D. Schellenberg, Shuo-Chien Ling, Kin Y. Mok, Maribel Patino, John Q. Trojanowski, Sigrun Roeber, William W. Seeley, Dennis W. Dickson, Vivianna M. Van Deerlin, Bruce L. Miller, Marla Gearing, Carles Gaig, Yee Kit Tai, and Christopher Morris
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0301 basic medicine ,Aging ,Neurodegenerative ,0302 clinical medicine ,C9orf72 ,Corticobasal degeneration ,2.1 Biological and endogenous factors ,Aetiology ,Alzheimer's Disease Related Dementias (ADRD) ,biology ,Neurodegeneration ,Brain ,Neurodegenerative Diseases ,Parkinson Disease ,Frontotemporal Dementia (FTD) ,Frontotemporal Dementia ,Neurological ,Frontotemporal dementia ,Tau protein ,Clinical Sciences ,Parkinsonism ,Article ,Pathology and Forensic Medicine ,03 medical and health sciences ,Cellular and Molecular Neuroscience ,Rare Diseases ,Basal Ganglia Diseases ,Parkinsonian Disorders ,Alzheimer Disease ,Microsatellite Repeat ,medicine ,Genetics ,Acquired Cognitive Impairment ,Autophagy ,Humans ,Neurology & Neurosurgery ,C9orf72 Protein ,Amyotrophic Lateral Sclerosis ,Neurosciences ,Alzheimer's Disease including Alzheimer's Disease Related Dementias (AD/ADRD) ,C9orf72 repeat expansion ,medicine.disease ,Stem Cell Research ,Brain Disorders ,030104 developmental biology ,biology.protein ,Cancer research ,Dementia ,Neurology (clinical) ,ALS ,Trinucleotide repeat expansion ,030217 neurology & neurosurgery - Abstract
Microsatellite repeat expansion disease loci can exhibit pleiotropic clinical and biological effects depending on repeat length. Large expansions in C9orf72 (100s-1000s of units) are the most common genetic cause of amyotrophic lateral sclerosis (ALS) and frontotemporal degeneration (FTD). However, whether intermediate expansions also contribute to neurodegenerative disease is not well understood. Several studies have identified intermediate repeats in Parkinson's disease patients, but the association was not found in autopsy-confirmed cases. We hypothesized that intermediate C9orf72 repeats are a genetic risk factor for corticobasal degeneration (CBD), a neurodegenerative disease that can be clinically similar to Parkinson's but has distinct tau protein pathology. Indeed, intermediate C9orf72 repeats were significantly enriched in autopsy-proven CBD (n = 354 cases, odds ratio = 3.59, p = 0.00024). While large C9orf72 repeat expansions are known to decrease C9orf72 expression, intermediate C9orf72 repeats result in increased C9orf72 expression in human brain tissue and CRISPR/cas9 knockin iPSC-derived neural progenitor cells. In contrast to cases of FTD/ALS with large C9orf72 expansions, CBD with intermediate C9orf72 repeats was not associated with pathologic RNA foci or dipeptide repeat protein aggregates. Knock-in cells with intermediate repeats exhibit numerous changes in gene expression pathways relating to vesicle trafficking and autophagy. Additionally, overexpression of C9orf72 without the repeat expansion leads to defects in autophagy under nutrient starvation conditions. These results raise the possibility that therapeutic strategies to reduce C9orf72 expression may be beneficial for the treatment of CBD.
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- 2019
36. Diabetes mellitus and tuberculosis in Korean adults: impact on tuberculosis incidence, recurrence and mortality
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Jonathan E. Golub, Sun Ha Jee, S Hong, Keum Ji Jung, Jonathan M. Samet, and Y Mok
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0301 basic medicine ,Pulmonary and Respiratory Medicine ,Adult ,Blood Glucose ,Male ,medicine.medical_specialty ,Tuberculosis ,National Health Programs ,030106 microbiology ,Cohort Studies ,03 medical and health sciences ,0302 clinical medicine ,Tuberculosis diagnosis ,Recurrence ,Risk Factors ,Internal medicine ,Republic of Korea ,Diabetes Mellitus ,Medicine ,Humans ,Mass Screening ,030212 general & internal medicine ,Prospective Studies ,Risk factor ,Prospective cohort study ,Aged ,business.industry ,Incidence (epidemiology) ,Incidence ,Hazard ratio ,Middle Aged ,medicine.disease ,Infectious Diseases ,Cohort ,Female ,business ,Cohort study - Abstract
sec id="st1"titleSETTING/titleThe prevalence of diabetes mellitus (DM) worldwide is increasing markedly, and many countries with rising rates also have a high incidence rate of tuberculosis (TB)./secsec id="st2"titleOBJECTIVE/titleTo investigate the relationships of fasting serum glucose (FSG) and DM with TB incidence, recurrence and mortality risk in a prospective cohort study in South Korea./secsec id="st3"titleDESIGN/titleOur study comprised 1 267 564 Koreans who received health insurance from the National Health Insurance System, had an initial medical evaluation between 1997 and 2000 and were prospectively followed biennially./secsec id="st4"titleRESULTS/titleParticipants with DM had a higher risk for incident TB (hazard ratio [HR] 1.81, 95%CI 1.71-1.91 in males, HR 1.33; 95%CI 1.20-1.47 in females) than those without DM. There was a strong positive trend for TB risk with rising FSG among males. The risk for recurrent TB among those with previous TB was significantly higher in males (HR 1.58, 95%CI 1.43-1.75) and in females with DM (HR 1.38, 95%CI 1.08-1.76). The increased risk of death from TB during follow-up was also significant in men (HR 1.91, 95%CI 1.87-1.95) and in women (HR 1.71, 95%CI 1.65-1.77)./secsec id="st5"titleCONCLUSIONS/titleA diagnosis of DM is a risk factor for TB, TB recurrence and death from TB. Screening for TB should be considered among people living with DM in Korea, particularly those with severe DM./sec.
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- 2019
37. Proton Pump Inhibitor-Associated Hypomagnesemia: A Retrospective Case-Control Study
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Laura G, Reed and Jean Y, Mok
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endocrine system ,Feature Articles ,humanities ,health care economics and organizations - Abstract
The results of this study showed an association between the use of prescription proton pump inhibitors and hypomagnesemia in a population of veterans.
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- 2019
38. Multi-ATOM: Ultrahigh-throughput single-cell quantitative phase imaging with subcellular resolution
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Ho Cheung Shum, Aaron T. Y. Mok, Bob M. F. Chung, Anson H. L. Tang, Wenwei Yan, Kelvin C. M. Lee, Maolin Wnag, Kenneth K. Y. Wong, Andy K. S. Lau, Godfrey Chi-Fung Chan, Hayden K.-H. So, Kathryn S.E. Cheah, and Kevin K. Tsia
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medicine.anatomical_structure ,Modality (human–computer interaction) ,Atom (programming language) ,business.industry ,Cell ,Resolution (electron density) ,Phase imaging ,medicine ,Computational biology ,Phase retrieval ,business ,Throughput (business) ,Biomedicine - Abstract
A growing body of evidence has substantiated the significance of quantitative phase imaging (QPI) in enabling cost-effective and label-free cellular assay, which provides useful insights into understanding biophysical properties of cells and their roles in cellular functions. However, available QPI modalities are limited by the loss of imaging resolution at high throughput and thus run short of sufficient statistical power at the single cell precision to define cell identities in a large and heterogeneous population of cells – hindering their utility in mainstream biomedicine and biology. Here we present a new QPI modality, coined multi-ATOM that captures and processes quantitative label-free single-cell images at ultra-high throughput without compromising sub-cellular resolution. We show that multi-ATOM, based upon ultrafast phase-gradient encoding, outperforms state-of-the-art QPI in permitting robust phase retrieval at a QPI throughput of >10,000 cell/sec, bypassing the need for interferometry which inevitably compromises QPI quality under ultrafast operation. We employ multi-ATOM for large-scale, label-free, multi-variate, cell-type classification (e.g. breast cancer sub-types, and leukemic cells versus peripheral blood mononuclear cells) at high accuracy (>94%). Our results suggest that multi-ATOM could empower new strategies in large-scale biophysical single-cell analysis with applications in biology and enriching disease diagnostics.
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- 2019
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39. Association of dementia with mortality among adults with Down syndrome older than 35 years
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Rosalyn, Hithersay, Carla M, Startin, Sarah, Hamburg, Kin Y, Mok, John, Hardy, Elizabeth M C, Fisher, Victor L J, Tybulewicz, Dean, Nizetic, and André, Strydom
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Male ,Adult ,Model organisms ,Heterozygote ,Apolipoprotein E4 ,Immunology ,Comorbidity ,Signalling & Oncogenes ,mental disorders ,Online First ,Humans ,Longitudinal Studies ,Age of Onset ,Mortality ,Original Investigation ,Human Biology & Physiology ,Epilepsy ,Research ,FOS: Clinical medicine ,Cell Biology ,Middle Aged ,Survival Analysis ,Featured ,England ,Female ,Dementia ,Down Syndrome ,Developmental Biology - Abstract
Key Points Question How does dementia status influence mortality in people with Down syndrome? Findings In a longitudinal study including 211 adults with Down syndrome 36 years and older, 27 people died during follow-up (mean, 28; range, 1-65 months), and dementia was the proximate cause of death in 70% of cases. Crude mortality rates were 5 times higher in those with dementia than those without. Meaning Nearly all older adults with Down syndrome now have dementia when they die, making this a vital population for researching disease progression, modifying factors, and potential treatments., Importance This work quantifies the fatal burden of dementia associated with Alzheimer disease in individuals with Down syndrome (DS). Objective To explore the association of dementia associated with Alzheimer disease with mortality and examine factors associated with dementia in adults with DS. Design, Settings and Participants Prospective longitudinal study in a community setting in England. Data collection began March 29, 2012. Cases were censored on December 13, 2017. The potential sample consisted of all adults 36 years and older from the London Down Syndrome Consortium cohort with 2 data times and dementia status recorded (N = 300); 6 withdrew from study, 28 were lost to follow-up, and 55 had a single data collection point at time of analysis. The final sample consisted of 211 participants, with 503.92 person-years’ follow-up. Exposures Dementia status, age, sex, APOE genotype, level of intellectual disability, health variables, and living situation. Main Outcomes and Measures Crude mortality rates, time to death, and time to dementia diagnosis with proportional hazards of predictors. Results Of the 211 participants, 96 were women (45.5%) and 66 (31.3%) had a clinical dementia diagnosis. Twenty-seven participants (11 female; mean age at death, 56.74 years) died during the study period. Seventy percent had dementia. Crude mortality rates for individuals with dementia (1191.85 deaths per 10 000 person-years; 95% CI, 1168.49-1215.21) were 5 times higher than for those without (232.22 deaths per 10 000 person-years; 95% CI, 227.67-236.77). For those with dementia, APOE ε4 carriers had a 7-fold increased risk of death (hazard ratio [HR], 6.91; 95% CI, 1.756-27.195). For those without dementia, epilepsy with onset after age 36 years was associated with mortality (HR, 9.66; 95% CI, 1.59-58.56). APOE ε4 carriers (HR, 4.91; 95% CI, 2.53-9.56), adults with early-onset epilepsy (HR, 3.61; 95% CI, 1.12-11.60), multiple health comorbidities (HR, 1.956; 95% CI, 1.087-3.519), and those living with family (HR, 2.14; 95% CI, 1.08-4.20) received significantly earlier dementia diagnoses. Conclusions and Relevance Dementia was associated with mortality in 70% of older adults with DS. APOE ε4 carriers and/or people with multiple comorbid health conditions were at increased risk of dementia and death, highlighting the need for good health care. For those who died without a dementia diagnosis, late-onset epilepsy was the only significant factor associated with death, raising questions about potentially undiagnosed dementia cases in this group., This study examines the association of dementia with mortality and examines factors associated with dementia predictors in adults with Down syndrome.
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- 2019
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40. MHD simulation of supersonic FRC merging corrected by non-invasive magnetic measurements
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D. Harashima, Sean Dettrick, Ts. Takahashi, T. Yoshino, Tomohiko Asai, Daichi Kobayashi, Y. Mok, Hiroshi Gota, and Tatsuhiro Watanabe
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010302 applied physics ,Physics ,Plasmoid ,Atmospheric-pressure plasma ,Mechanics ,01 natural sciences ,010305 fluids & plasmas ,Magnetic field ,Physics::Plasma Physics ,0103 physical sciences ,Total air temperature ,Initial value problem ,Supersonic speed ,Magnetic pressure ,Magnetohydrodynamics ,Instrumentation - Abstract
In this study, a newly developed correction method with external magnetic measurements for the magnetohydrodynamics (MHD) simulation of the collisional merging formation of a field-reversed configuration (FRC) realized the estimation of the internal structure of the FRCs without invasive internal measurements. In the collisional merging formation of FRCs, an FRC is formed via merging of two initial FRC-like plasmoids at supersonic/Alfvénic velocity. An invasive diagnostic may also interfere with the collisional merging formation process. A two-dimensional resistive MHD simulation was conducted to evaluate the global behavior and internal structure of FRCs in the collisional merging formation process without invasive measurements. This code simulated the initial formation and collisional merging processes of FRCs including discharge circuits. However, the translation velocity and the pressure of initial FRCs did not simultaneously agree with the experimental values because the magnetic pressure gradient in each formation region could not be reproduced without the artificial adjustment of the initial condition. The experimentally measured current distribution was given as the initial condition of the circuit calculation in the developed correction method. The initial FRCs were successfully translated at the translation velocity and plasma pressure in the corrected simulation, both of which were equivalent to the experiments. The properties of the merged FRCs in the experiments such as volume, total temperature, and average electron density were reproduced in the corrected simulation. The detailed radial profile of the internal magnetic field of the FRC was also measured and found to agree very well with the simulation results.
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- 2021
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41. Performance of trigger tools in identifying adverse drug events in emergency department patients: a validation study
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Catherine P. Y. Mok, Catherine Parcero, Eugenia Yu, Linda Dempster, Andrei Karpov, Corinne M. Hohl, and Chandima Panditha
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Pharmacology ,medicine.medical_specialty ,business.industry ,030503 health policy & services ,Medical record ,Surveillance Methods ,Emergency department ,Confidence interval ,Clinical pharmacy ,03 medical and health sciences ,0302 clinical medicine ,Public health surveillance ,Emergency medicine ,Health care ,Medicine ,Pharmacology (medical) ,030212 general & internal medicine ,0305 other medical science ,Prospective cohort study ,business - Abstract
Aims Trigger tools are retrospective surveillance methods that can be used to identify adverse drug events (ADEs), unintended and harmful effects of medications, in medical records. Trigger tools are used in quality improvement, public health surveillance and research activities. The objective of the study was to evaluate the performance of trigger tools in identifying ADEs. Methods This study was a sub-study of a prospective cohort study which enrolled adults presenting to one tertiary care emergency department. Clinical pharmacists evaluated patients for ADEs at the point-of-care. Twelve months after the prospective study's completion, the patients' medical records were reviewed using eight different trigger tools. ADEs identified using each trigger tool were compared with events identified at the point-of-care. The primary outcome was the sensitivity of each trigger tool for ADEs. Results Among 1151 patients, 152 (13.2%, 95% confidence intervals (CI) 11.4, 15.3%) were diagnosed with one or more ADEs at the point-of-care. The sensitivity of the trigger tools for detecting ADEs ranged from 2.6% (95% CI 0.7, 6.6%) to 15.8% (95% CI 10.6, 22.8%). Their specificity varied from 99.3% (95% CI 98.6, 99.7) to 100% (95% CI 99.6, 100%). Conclusion The trigger tools examined had poor sensitivity for identifying ADEs in emergency department patients, when applied manually and in retrospect. Reliance on these methods to detect ADEs for quality improvement, surveillance, and research activities is likely to underestimate their occurrence, and may lead to biased estimates.
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- 2016
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42. Burkholderia CepaciaExit-Site Infection in Peritoneal Dialysis Patients—Clinical Characteristics and Treatment Outcomes
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Lorraine P Y Kwan, Wai Kei Lo, Jasper Fuk-Woo Chan, Tak Mao Chan, Desmond Y H Yap, Terence Yip, and Maggie M Y Mok
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Male ,0301 basic medicine ,medicine.drug_class ,Intrinsic resistance ,medicine.medical_treatment ,030106 microbiology ,Treatment outcome ,Antibiotics ,030232 urology & nephrology ,Peritonitis ,Burkholderia cepacia ,Microbiology ,Peritoneal dialysis ,03 medical and health sciences ,Catheters, Indwelling ,0302 clinical medicine ,Drug Resistance, Bacterial ,medicine ,Humans ,Device Removal ,Aged ,Retrospective Studies ,Exit site ,biology ,business.industry ,Burkholderia Infections ,Original Articles ,General Medicine ,Middle Aged ,medicine.disease ,biology.organism_classification ,Catheter-Related Infections ,Anti-Bacterial Agents ,Treatment Outcome ,Burkholderia ,Nephrology ,Kidney Failure, Chronic ,Female ,business ,Peritoneal Dialysis - Abstract
BackgroundBurkholderia cepacia is a hardy bacterium with intrinsic resistance to multiple antibiotics and high transmissibility. Opportunistic healthcare-associated B. cepacia infections among immunocompromised or critically ill patients have been reported, but there is limited data on the clinical characteristics and treatment outcomes of exit-site infection (ESI) in peritoneal dialysis (PD) patients.Patients and methodsPatients who suffered from B. cepacia ESI from 1 January 2004 to 31 December 2014 were reviewed. The clinical characteristics and treatment outcomes of the patients and the antibiotic susceptibility patterns of the bacterial isolates were analyzed.ResultsTwenty-two patients were included for analysis. Eight patients (36.4%) had medical conditions which impaired host immunity, while 7 (31.8%) had pre-existing skin abnormalities. Three patients (13.6%) progressed to tunnel-tract infection and another 3 patients (13.6%) developed associated peritonitis. Fifteen patients (68.2%) responded to medical treatment while 7 (31.8%) required catheter removal. Eleven patients (50.0%) had recurrent B. cepacia ESI, which occurred at 7.8 months (95% confidence interval [CI] 0.1 – 19.4 months) after the first episode. Most B. cepacia strains were susceptible to ceftazidime (95.5%), piperacillin/tazobactam (95.5%), and piperacillin (90.9%). Besides aminoglycosides (80 – 100%), high rates of resistance were also observed for ticarcillin/clavulanate (90.9%).ConclusionBurkholderia cepacia ESI is associated with low rates of tunnel-tract infection or peritonitis, but the risk of recurrence is high. Most cases can be managed with medical treatment alone, although one third of patients might require catheter removal.
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- 2016
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43. HLA-DRB*1501 associations with magnetic resonance imaging measures of grey matter pathology in multiple sclerosis
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John Hardy, Henry Houlden, Matteo Pardini, Declan T. Chard, Kin Y. Mok, Rebecca S. Samson, Carmen Tur, Zheng Liu, Claudia A. M. Wheeler-Kingshott, Nils Muhlert, Özgür Yaldizli, Tarek A. Yousry, David H. Miller, and Varun Sethi
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Adult ,Male ,0301 basic medicine ,medicine.medical_specialty ,Pathology ,Grey matter ,Multiple Sclerosis ,Neurology ,Genotype ,Human leukocyte antigen ,Multiple sclerosis ,gray matter ,magnetization transfer ratio ,HLA-DRB⁎1501 ,cortical lesion ,Polymorphism, Single Nucleotide ,Disability Evaluation ,Young Adult ,03 medical and health sciences ,0302 clinical medicine ,medicine ,Humans ,Genetic Predisposition to Disease ,Magnetization transfer ,Gray Matter ,Genotyping ,Magnetization transfer ratio ,Cerebral Cortex ,medicine.diagnostic_test ,business.industry ,HLA-DRB∗1501 ,Haplotype ,Magnetic resonance imaging ,Cortical lesion ,Organ Size ,General Medicine ,Middle Aged ,medicine.disease ,Magnetic Resonance Imaging ,Neurology (clinical) ,030104 developmental biology ,medicine.anatomical_structure ,Haplotypes ,Female ,business ,030217 neurology & neurosurgery ,HLA-DRB1 Chains - Abstract
Background The HLA-DRB*1501 haplotype influences the risk of developing multiple sclerosis (MS), but it is not known how it affects grey matter pathology. Aim To assess HLA-DRB * 1501 effects on magnetic resonance imaging (MRI) cortical grey matter pathology. Methods Whole and lesional cortical grey matter volumes, lesional and normal-appearing grey matter magnetization transfer ratio were measured in 85 people with MS and 36 healthy control subjects. HLA-DRB * 1501 haplotype was determined by genotyping (rs3135388). Results No significant differences were observed in MRI measures between the HLA-DRB * 1501 subgroups. Conclusions The HLA-DRB * 1501 haplotype is not strongly associated with MRI-visible grey matter pathology.
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- 2016
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44. Do we need transbronchial lung biopsy if we have bronchoalveolar lavage Xpert® MTB/RIF?
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Tunn Ren Tay, C Siao, Pei Yee Tiew, Thean Yen Tan, Hang Siang Wong, Y. Mok, and J W Kam
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0301 basic medicine ,Pulmonary and Respiratory Medicine ,Pathology ,medicine.medical_specialty ,Tuberculosis ,030106 microbiology ,Time to treatment ,Gastroenterology ,03 medical and health sciences ,fluids and secretions ,0302 clinical medicine ,Pulmonary tuberculosis ,Internal medicine ,Biopsy ,medicine ,030212 general & internal medicine ,Pulmonary pathology ,integumentary system ,medicine.diagnostic_test ,business.industry ,Transbronchial lung biopsy ,respiratory system ,medicine.disease ,respiratory tract diseases ,Infectious Diseases ,Bronchoalveolar lavage ,Predictive value of tests ,business - Abstract
Background Studies evaluating the role of transbronchial lung biopsy (TBLB) in diagnosing pulmonary tuberculosis (PTB) date back decades and have shaped current practice. However, with the recent advent of bronchoalveolar lavage (BAL) Xpert® MTB/RIF, it is time to re-evaluate the role of TBLB. Objective To assess the impact of BAL and TBLB with the addition of BAL Xpert on diagnostic PTB yields and time to treatment initiation in sputum-scarce or acid-fast bacilli (AFB) smear-negative PTB patients. Methods We retrospectively reviewed all sputum-scarce or AFB smear-negative patients who underwent both BAL and TBLB for suspected PTB between March 2011 and October 2013. Xpert was performed on all BAL specimens. Results Of 158 patients included in our analysis, 44 were culture-proven PTB. Ninety-four per cent of the patients had AFB smear-negative BAL samples. The sensitivity and specificity of Xpert in AFB smear-negative BAL samples were respectively 60% and 98%. The addition of BAL Xpert expedited the institution of PTB treatment while having diagnostic yields comparable to those of conventional BAL with TBLB. Conclusions The use of BAL Xpert may obviate the need for TBLB in increasing the diagnostic yield of PTB in sputum-scarce or AFB smear-negative patients.
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- 2016
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45. A web-based design support system for fashion technical sketches
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C.W.M. Yuen, Jie Xu, Rwy W. Y. Yee, and Py Y. Mok
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Polymers and Plastics ,Fashion design ,Multimedia ,business.industry ,Computer science ,Materials Science (miscellaneous) ,020207 software engineering ,02 engineering and technology ,Client-side ,computer.software_genre ,General Business, Management and Accounting ,Sketch ,Workflow ,Web design ,0202 electrical engineering, electronic engineering, information engineering ,Business, Management and Accounting (miscellaneous) ,Web application ,020201 artificial intelligence & image processing ,The Internet ,business ,computer ,Graphical user interface - Abstract
Purpose – To better respond to today’s volatile and changing fashion market, the purpose of this paper is to develop a web-based design support system that enables users to design realistic and interesting skirts in the form of technical sketches over the internet. Design/methodology/approach – The proposed system mainly consists of a sketch representation and composing method (SRCM), a graphic user interface (GUI) and a controller. The SRCM is implemented at the server end that generates technical sketches according to user defined parameters and features via the web-based GUI at the client side. The controller manages the workflows between the server and the clients. Findings – To evaluate the effectiveness of the proposed system, a survey was conducted by inviting 30 subjects (professional designers or undergraduate students studying fashion design) to have trial run of the system in Hong Kong and in the USA. Positive comments and feedbacks were received, and valuable suggestions were also obtained in regard to the prototype system. Originality/value – Compared with traditional computer-aided design (CAD) systems, the proposed system is more effective and easier to operate as users can create technical sketches in accurate proportions with simple computer operations in a few mouse clicks. Besides, the output sketches are fully compatible with most commercial CAD software. The system is developed based on web technologies, thus fashion sketches can be easily designed using any computer connected to the internet; it can be implemented on Android or iOS platform in the future.
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- 2016
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46. VP13.11: Fatty filum terminale: a case report and review of literature
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Y. Mok
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Reproductive Medicine ,Radiological and Ultrasound Technology ,Obstetrics and Gynecology ,Radiology, Nuclear Medicine and imaging ,General Medicine - Published
- 2020
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47. Differential Associations of Apolipoprotein E ε4 Genotype With Attentional Abilities Across the Life Span of Individuals With Down Syndrome
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Andre Strydom, Hana D'Souza, Kin Y. Mok, Rosalyn Hithersay, R. Asaad Baksh, Michael S.C. Thomas, Carla M. Startin, Sarah Hamburg, Luke Mason, and John Hardy
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Apolipoprotein E ,Down syndrome ,medicine.medical_specialty ,Cross-sectional study ,business.industry ,Cognition ,General Medicine ,Audiology ,medicine.disease ,medicine ,Allele ,Alzheimer's disease ,Young adult ,Association (psychology) ,business - Abstract
Importance Risk of Alzheimer disease (AD) is particularly high for individuals with Down syndrome (DS). The e4 allele of the apolipoprotein E gene (APOE e4) is associated with an additional risk for AD. In typical development, there is evidence that theAPOE e4 genotype is associated with an early cognitive advantage. Here we investigate associations ofAPOE e4 with attention across the life span of individuals with DS. Objective To investigate associations betweenAPOE e4 and attentional abilities in young children and in adults with DS. Design, Settings, and Participants In this cross-sectional study, data were collected from 80 young children with DS (8-62 months of age) and 240 adults with DS (16-71 years of age) during the period from 2013 to 2018 at a research center to examine the association betweenAPOEstatus (e4 carrier vs e4 noncarrier) and attentional abilities. Exposure APOEstatus (e4 carrier vs e4 noncarrier). Main Outcomes and Measures For the children, attentional ability was assessed using an eye-tracking paradigm, the gap-overlap task; the size of the gap effect was the primary outcome. For the adults, attentional ability was assessed using the CANTAB simple reaction time task; the standard deviation of response time latencies was the primary outcome. Cross-sectional developmental trajectories were constructed linking attentional ability with age in e4 carriers and e4 noncarriers for children and adults separately. Results The child sample comprised 23 e4 carriers and 57 e4 noncarriers. The adult sample comprised 61 e4 carriers and 179 e4 noncarriers. For the children, a significant difference between trajectory intercepts (ηp2 = 0.14) indicated that e4 carriers (B = 100.24 [95% CI, 18.52-181.96]) exhibited an attentional advantage over e4 noncarriers (B = 314.78 [95% CI, 252.17-377.39]). There was an interaction betweenAPOEstatus and age (ηp2 = 0.10); while the gap effect decreased with age for e4 noncarriers (B = −4.58 [95% CI, −6.67 to −2.48]), reflecting the development of the attention system, there was no change across age in e4 carriers (B = 0.77 [95% CI, −1.57 to 3.12]). For the adults, there was no main effect of e4 carrier status, but there was an interaction betweenAPOEstatus and age (B = 0.02 [95% CI, 0.004-0.07]), so that e4 carriers had poorer attentional ability than e4 noncarriers at older ages. Conclusions and Relevance APOE e4 is associated with an attentional advantage early in development and a disadvantage later in life for individuals with DS, similar to the pattern reported in typical development. Understanding the differential role ofAPOEacross the life span is an important step toward future interventions.
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- 2020
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48. Identification of Risk Loci for Parkinson Disease in Asians and Comparison of Risk Between Asians and Europeans
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Yin Xia Chao, Louis C.S. Tan, Rong Peng, Yongping Chen, Ai Huey Tan, Kyuyoung Song, Jing Yang, Anne Y.Y. Chan, Yuming Xu, Yaping Yan, Changhe Shi, Jianjun Liu, Juei-Jueng Lin, Lulu Jiang, Mike A. Nalls, Wing Lok Au, Shen-Yang Lim, Michelle M. Lian, Zhong Pei, Huifang Shang, Wataru Satake, Eng-King Tan, Azlina Ahmad Annuar, Wee-Yang Meah, Vincent Mok, Chun-Feng Liu, Cheng-Jie Mao, Kumar M. Prakash, Baorong Zhang, Jia Nee Foo, Ling Chen, Yih-Ru Wu, Jia Lun Lim, Chiea Chuen Khor, Beom S. Jeon, Woon-Puay Koh, Cornelis Blauwendraat, Kin Y. Mok, Tatsushi Toda, Renshi Xu, Ebonne Yulin Ng, Elaine Guo Yan Chew, Shi Qi Mok, Sun Ju Chung, and Moses Tandiono
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education.field_of_study ,Genetic heterogeneity ,business.industry ,Population ,Genome-wide association study ,Disease ,Odds ratio ,03 medical and health sciences ,0302 clinical medicine ,Meta-analysis ,Cohort ,Medicine ,030212 general & internal medicine ,Neurology (clinical) ,education ,business ,030217 neurology & neurosurgery ,Demography ,Genetic association - Abstract
Importance Large-scale genome-wide association studies in the European population have identified 90 risk variants associated with Parkinson disease (PD); however, there are limited studies in the largest population worldwide (ie, Asian). Objectives To identify novel genome-wide significant loci for PD in Asian individuals and to compare genetic risk between Asian and European cohorts. Design Setting, and Participants Genome-wide association data generated from PD cases and controls in an Asian population (ie, Singapore/Malaysia, Hong Kong, Taiwan, mainland China, and South Korea) were collected from January 1, 2016, to December 31, 2018, as part of an ongoing study. Results were combined with inverse variance meta-analysis, and replication of top loci in European and Japanese samples was performed. Discovery samples of 31 575 individuals passing quality control of 35 994 recruited were used, with a greater than 90% participation rate. A replication cohort of 1 926 361 European-ancestry and 3509 Japanese samples was analyzed. Parkinson disease was diagnosed using UK Parkinson’s Disease Society Brain Bank Criteria. Main Outcomes and Measures Genotypes of common variants, association with disease status, and polygenic risk scores. Results Of 31 575 samples identified, 6724 PD cases (mean [SD] age, 64.3 [10] years; age at onset, 58.8 [10.6] years; 3472 [53.2%] men) and 24 851 controls (age, 59.4 [11.4] years; 11 030 [45.0%] men) were analyzed in the discovery study. Eleven genome-wide significant loci were identified; 2 of these loci were novel (SV2CandWBSCR17) and 9 were previously found in Europeans. Replication in European-ancestry and Japanese samples showed robust association forSV2C(rs246814; odds ratio, 1.16; 95% CI, 1.11-1.21;P = 1.17 × 10−10in meta-analysis of discovery and replication samples) but showed potential genetic heterogeneity atWBSCR17(rs9638616;I2=67.1%;P = 3.40 × 10−3for hetereogeneity). Polygenic risk score models including variants at these 11 loci were associated with a significant improvement in area under the curve over the model based on 78 European loci alone (63.1% vs 60.2%;P = 6.81 × 10−12). Conclusions and Relevance This study identified 2 apparently novel gene loci and found 9 previously identified European loci to be associated with PD in this large, meta–genome-wide association study in a worldwide population of Asian individuals and reports similarities and differences in genetic risk factors between Asian and European individuals in the risk for PD. These findings may lead to improved stratification of Asian patients and controls based on polygenic risk scores. Our findings have potential academic and clinical importance for risk stratification and precision medicine in Asia.
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- 2020
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49. Evaluation of Translation Velocity Control by Auxiliary Coils for the Collisional Merging Formation of FRCs by 2-D Resistive MHD Simulation
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Junichi Sekiguchi, Y. Mok, Tsutomu Takahashi, Sean Dettrick, Daichi Kobayashi, Michl Binderbauer, Hiroshi Gota, Toshiki Tajima, and Tomohiko Asai
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Physics ,Resistive touchscreen ,Field-reversed configuration ,Translational velocity ,Mechanics ,Magnetohydrodynamics ,Condensed Matter Physics - Published
- 2020
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50. 0574 Prevalence and Characteristics of Rapid Eye Movement Obstructive Sleep Apnoea (REM OSA) in a Multi-Ethnic OSA Cohort
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Hang Siang Wong, Y. Poh, and Y. Mok
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Pediatrics ,medicine.medical_specialty ,medicine.diagnostic_test ,business.industry ,musculoskeletal, neural, and ocular physiology ,Epworth Sleepiness Scale ,Eye movement ,Apnea ,Polysomnography ,medicine.disease ,Sleep in non-human animals ,nervous system diseases ,respiratory tract diseases ,Obstructive sleep apnea ,stomatognathic system ,Physiology (medical) ,Severity of illness ,Cohort ,Medicine ,Neurology (clinical) ,medicine.symptom ,business ,psychological phenomena and processes - Abstract
Introduction Recent studies have shown that REM OSA is associated with increased incidence of hypertension and insulin resistance. However, there is a lack of Asian data on REM OSA. Our study aimed to examine the prevalence and characteristics of REM OSA in a multi-ethnic OSA cohort. Methods This was a retrospective observational study of all patients who underwent an overnight diagnostic polysomnography at a Singapore tertiary hospital from 1st August 2017 to 31st August 2018. All patients with a diagnosis of OSA (Apnoea Hypopnea Index (AHI) ≥5) were included in the study. REM OSA is defined as an overall AHI≥5, REM AHI/Non REM (NREM) AHI>2, NREM AHI Results 457 OSA subjects were included in the analysis. 19% (87/457) had REM OSA. Univariate analysis showed that REM OSA was more prevalent among female OSA than male OSA [34/115 (29.6%) versus 53/342 (15.5%) respectively, p Conclusion REM OSA was common in our OSA cohort and had higher prevalence in female and milder disease severity compared to non REM OSA. However, we did not find an increased prevalence of hypertension or diabetes mellitus in REM OSA. Further population-based study on REM OSA is needed to understand this phenotype better. Support NIL
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- 2020
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