Modeling and identification of gene regulatory networks: A Granger causality approach

It is of increasing interest in systems biology to discover gene regulatory networks (GRNs) from time-series genomic data, i.e., to explore the interactions among a large number of genes and gene products over time. Currently, one common approach is based on Granger causality, which models the time-series genomic data as a vector autoregressive (VAR) process and estimates the GRNs from the VAR coefficient matrix. The main challenge for identification of VAR models is the high dimensionality of genes and limited number of time points, which results in statistically inefficient solution and high computational complexity. Therefore, fast and efficient variable selection techniques are highly desirable. In this paper, an introductory review of identification methods and variable selection techniques for VAR models in learning the GRNs will be presented. Furthermore, a dynamic VAR (DVAR) model, which accounts for dynamic GRNs changing with time during the experimental cycle, and its identification methods are introduced. © 2010 IEEE.published_or_final_versionThe 9th International Conference on Machine Learning and Cybernetics (ICMLC 2010), Qingdao, China, 11-14 July 2010. In Proceedings of the 9th ICMLC, 2010, v. 6, p. 3073-307

Risk Factors for Development of Paradoxical Response During Antituberculosis Therapy in HIV-Negative Patients

The risk factors for development of paradoxical response were studied in a cohort of 104 patients with culture-documented Mycobacterium tuberculosis infection. Paradoxical deterioration occurred in 16 (15.4%) patients (case group) during antituberculosis therapy, involving lungs and pleura (n=4), spine and paraspinal tissue (n=5), intracranium (n=3), peritoneum (n=2), bone and joint (n=1), and lymph node (n=1). The median time from commencement of treatment to paradoxical deterioration was 56 days (range, 20-109 days). Compared with 53 patients without clinical deterioration after antituberculosis therapy (control group), patients with paradoxical response were more likely to have extrapulmonary involvement (62.5% vs. 17.0%; P<0.05) at initial diagnosis, to have lower baseline lymphocyte counts (672±315 cells/μl vs. 1,328±467 cells/μl; P<0.001), and to exhibit a greater surge in lymphocyte counts (627±465 cells/μl vs. 225±216 cells/ μl; P<0.05) during paradoxical response. Further studies on lymphocyte subsets and cytokine levels would be useful in understanding the exact immunological mechanisms involved in immunorestitution.postprin

Pathway of psychiatric care in Hong Kong

published_or_final_versio

Early intervention for psychotic disorders: Real-life implementation in Hong Kong

Hong Kong is among the first few cities in Asia to have implemented early intervention for psychosis in 2001. Substantial changes in psychosis service have since taken place. We reviewed available outcome data in Hong Kong, with reference to the philosophy of early intervention in psychosis, discussing experience and lessons learned from the implementation process, and future opportunities and challenges. Data accumulated in the past decade provided evidence for the benefits and significance of early intervention programmes: patients under the care of early intervention service showed improved functioning, milder symptoms, and fewer hospitalizations and suicides. Early intervention is more cost-effective compared with standard care. Stigma and misconception remains an issue, and public awareness campaigns are underway. In recent years, a critical mass is being formed, and Hong Kong has witnessed the unfolding of public service extension, new projects and organizations, and increasing interest from the community. Several major platforms are in place for coherent efforts, including the public Early Assessment Service for Young people with psychosis (EASY) programme, the Psychosis Studies and Intervention (PSI) research unit, the independent Hong Kong Early Psychosis Intervention Society (EPISO), the Jockey Club Early Psychosis (JCEP) project, and the postgraduate Psychological Medicine (Psychosis Studies) programme. The first decade of early intervention work has been promising; consolidation and further development is needed on many fronts of research, service and education. © 2012 Elsevier B.V.postprin

Influence of Maternal Infection and Pregnancy Complications on Cord Blood Telomere Length

BACKGROUND: Exposure to suboptimal intrauterine environment might induce structural and functional changes that can affect neonatal health. Telomere length as an important indicator of cellular health has been associated with increased risk for disease development. OBJECTIVES: This study was aimed to examine the independent and combined effects of maternal, obstetric, and foetal factors on cord blood telomere length (TL). METHODS: Pregnant women at the gestational age of 20th to 24th week who attended the antenatal clinic of a major local hospital in Hong Kong were recruited. Participants were asked to complete a questionnaire on demographics, health-related quality of life, and history of risk behaviors. Medical history including pregnancy complications and neonatal outcomes was obtained from electronic medical records of both mother and neonate. Umbilical cord blood was collected at delivery for TL determination. RESULTS: A total of 753 pregnant women (average age: 32:18 ± 4:51 years) were recruited. The prevalence of maternal infection, anaemia, and hypertension during pregnancy was 30.8%, 30.0%, and 6.0%, respectively. The adjusted regression model displayed that maternal infection was negatively associated with cord blood TL (β = −0:18, p = 0:026). This association became even stronger in the presence of antenatal anaemia, hypertension, delivery complications, or neonatal jaundice (β = −0:25 to −0.45). Conclusions. This study consolidates evidence on the impact of adverse intrauterine environment at the cellular level. Maternal infection was significantly associated with shorter cord blood TL in a unique manner such that its presence may critically determine the susceptibility of telomere to other factors

The Hong Kong mental morbidity survey: background and study design

Mental disorders are highly prevalent conditions with immense disease burden. To inform health and social services policy formulation, local psychiatric epidemiological data are required. The Hong Kong Mental Morbidity Survey is a 3-year population-based study in which 5700 community-dwelling Chinese adults aged between 16 and 75 years were interviewed with the aim of evaluating the prevalence, co-morbidity, functional impairment, physical morbidity, and social determinants of significant mental disorders in the population. This paper describes the background and design of the survey, and is the first territory-wide psychiatric epidemiological study in Hong Kong. 精神障礙非常普遍，且對社會造成巨大的疾病負擔。收集本地精神病流行病學資料，對計劃相關的衛生及社會服務政策至為重要。香港精神健康調查是一個為期3年，以人口為基礎的大型研究，透過對5700名介乎16歲至75歲之華裔市民進行精神健康評估，檢視重要的精神障礙的現患率、共病、功能障礙、身體疾病以及社會決定因素。本文闡述這項首個全港大型精神病流行病研究的背景和設計。published_or_final_versio

Mutation spectrum of 122 hemophilia A families from Taiwanese population by LD-PCR, DHPLC, multiplex PCR and evaluating the clinical application of HRM

<p>Abstract</p> <p>Background</p> <p>Hemophilia A represents the most common and severe inherited hemorrhagic disorder. It is caused by mutations in the F8 gene, which leads to a deficiency or dysfunctional factor VIII protein, an essential cofactor in the factor X activation complex.</p> <p>Methods</p> <p>We used long-distance polymerase chain reaction and denaturing high performance liquid chromatography for mutation scanning of the F8 gene. We designed the competitive multiplex PCR to identify the carrier with exonal deletions. In order to facilitate throughput and minimize the cost of mutation scanning, we also evaluated a new mutation scanning technique, high resolution melting analysis (HRM), as an alternative screening method.</p> <p>Results</p> <p>We presented the results of detailed screening of 122 Taiwanese families with hemophilia A and reported twenty-nine novel mutations. There was one family identified with whole exons deletion, and the carriers were successfully recognized by multiplex PCR. By HRM, the different melting curve patterns were easily identified in 25 out of 28 cases (89%) and 15 out of 15 (100%) carriers. The sensitivity was 93 % (40/43). The overall mutation detection rate of hemophilia A was 100% in this study.</p> <p>Conclusion</p> <p>We proposed a diagnostic strategy for hemophilia A genetic diagnosis. We consider HRM as a powerful screening tool that would provide us with a more cost-effective protocol for hemophilia A mutation identification.</p

Fumarate Analogs Act as Allosteric Inhibitors of the Human Mitochondrial NAD(P)+-Dependent Malic Enzyme

Human mitochondrial NAD(P)+-dependent malic enzyme (m-NAD(P)-ME) is allosterically activated by the four-carbon trans dicarboxylic acid, fumarate. Previous studies have suggested that the dicarboxylic acid in a trans conformation around the carbon-carbon double bond is required for the allosteric activation of the enzyme. In this paper, the allosteric effects of fumarate analogs on m-NAD(P)-ME are investigated. Two fumarate-insensitive mutants, m-NAD(P)-ME_R67A/R91A and m-NAD(P)-ME_K57S/E59N/K73E/D102S, as well as c-NADP-ME, were used as the negative controls. Among these analogs, mesaconate, trans-aconitate, monomethyl fumarate and monoethyl fumarate were allosteric activators of the enzyme, while oxaloacetate, diethyl oxalacetate, and dimethyl fumarate were found to be allosteric inhibitors of human m-NAD(P)-ME. The IC50 value for diethyl oxalacetate was approximately 2.5 mM. This paper suggests that the allosteric inhibitors may impede the conformational change from open form to closed form and therefore inhibit m-NAD(P)-ME enzyme activity

Bell's palsy following vaccination with mRNA (BNT162b2) and inactivated (CoronaVac) SARS-CoV-2 vaccines: a case series and nested case-control study

BACKGROUND: Bell's palsy is a rare adverse event reported in clinical trials of COVID-19 vaccines. However, to our knowledge no population-based study has assessed the association between the inactivated SARS-CoV-2 vaccines and Bell's palsy. The aim of this study was to evaluate the risk of Bell's palsy after BNT162b2 and CoronaVac vaccination. METHODS: In this case series and nested case-control study done in Hong Kong, we assessed the risk of Bell's palsy within 42 days following vaccination with BNT162b2 (Fosun–BioNTech [equivalent to Pfizer–BioNTech]) or CoronaVac (from Sinovac Biotech, Hong Kong) using data from voluntary surveillance reporting with the Hospital Authority, the COVID-19 Vaccine Adverse Event Online Reporting system for all health-care professionals, and the Hospital Authority's territory-wide electronic health records from the Clinical Data Analysis and Reporting System. We described reported cases of Bell's palsy among vaccine recipients (aged 18–110 years for CoronaVac and aged 16–110 years for BNT162b2). We compared the estimated age-standardised incidence of clinically confirmed cases among individuals who had received the CoronaVac or BNT162b2 vaccination (up to 42 days before presentation) with the background incidence in the population. A nested case-control study was also done using conditional logistic regression to estimate the odds ratio (OR) for risk of Bell's palsy and vaccination. Cases and controls were matched (1:4) by age, sex, admission setting, and admission date. FINDINGS: Between February 23 and May 4, 2021, 451 939 individuals received the first dose of CoronaVac and 537 205 individuals received the first dose of BNT162b2. 28 clinically confirmed cases of Bell's palsy were reported following CoronaVac and 16 cases were reported following BNT162b2. The age-standardised incidence of clinically confirmed Bell's palsy was 66·9 cases per 100 000 person-years (95% CI 37·2 to 96·6) following CoronaVac vaccination and 42·8 per 100 000 person-years (19·4 to 66·1) for BNT162b2 vaccination. The age-standardised difference for the incidence compared with the background population was 41·5 (95% CI 11·7 to 71·4) for CoronaVac and 17·0 (−6·6 to 40·6) for BNT162b2, equivalent to an additional 4·8 cases per 100 000 people vaccinated for CoronaVac and 2·0 cases per 100 000 people vaccinated for BNT162b2. In the nested case-control analysis, 298 cases were matched to 1181 controls, and the adjusted ORs were 2·385 (95% CI 1·415 to 4·022) for CoronaVac and 1·755 (0·886 to 3·477) for BNT162b2. INTERPRETATION: Our findings suggest an overall increased risk of Bell's palsy after CoronaVac vaccination. However, the beneficial and protective effects of the inactivated COVID-19 vaccine far outweigh the risk of this generally self-limiting adverse event. Additional studies are needed in other regions to confirm our findings. FUNDING: The Food and Health Bureau of the Government of the Hong Kong Special Administrative Region, China. TRANSLATION: For the Chinese translation of the abstract see Supplementary Materials section