Regulatory role of miR-142-3p on the functional hepatic cancer stem cell marker CD133

Tumor relapse after therapy typifies hepatocellular carcinoma (HCC) and is believed to be attributable to residual cancer stem cells (CSCs) that survive treatment. We have previously identified a CSC population derived from HCC that is characterized by CD133. Despite our growing knowledge of the importance of this subset of cells in driving HCC, the regulatory mechanism of CD133 is not known. Epigenetic changes are believed to be essential in the control of cancer and stem cells. Here, we report the epigenetic regulation of CD133 by miR-142-3p. The interaction between CD133 and miR-142-3p was identified by in silico prediction and substantiated by luciferase reporter analysis. Expression of CD133 was found to be inversely correlated with miR-142-3p in HCC clinical samples as well as in cell lines. Importantly, lower miR-142-3p expression in HCC was significantly associated with worst survival. Functional studies with miR-142-3p stably transduced in HCC cells demonstrated a diminished ability to self-renew, initiate tumor growth, invade, migrate, induce angiogenesis and resist chemotherapy. Rescue experiments whereby CD133 and miR-142-3p is simultaneously overexpressed compensated the deregulated ability of the cells to confer these features. Thus, miR-142-3p directly targets CD133 to regulate its ability to confer cancer and stem cell-like features in HCC.published_or_final_versio

Evaluation of deformity and hand function in cerebral palsy patients

<p>Abstract</p> <p>Background</p> <p>A cross-sectional study was performed to describe the upper limb deformity and function in cerebral palsy patients and to determine the correlation of deformity, spasticity, motor control, and sensation to hand function in the said population.</p> <p>Materials and methods</p> <p>Thirty patients satisfying our inclusion criteria underwent physical, sensory, and functional assessment using a standard protocol. Physical assessment included documentation of the degree of spasticity, deformity and muscle control. Sensation was tested using static two-point discrimination test and stereognosis test. Melbourne Assessment of the Unilateral Upper Limb Function Test (MAULF), Functional Hand Grip Test (FHGT), and Functional Independence Measure for children (WeeFIM) were used to evaluate hand function. Deformity, spasticity, motor control, and sensation were analyzed for correlation with hand function using Pearson Correlation analysis. A p-value of less than 0.05 was considered statistically significant.</p> <p>Results</p> <p>Functional deficits of the hand increased with increasing severity of deformity and spasticity. Tetraplegics were most affected by spasticity, deformity, poor motor control, sensory and functional deficits. Triplegics, followed by diplegics had more functional upper limbs in terms of the MAULF and FHGT scores. Unilaterally affected patients (triplegics and hemiplegics) scored better in performance of activities of daily living. The MAULF and FHGT had a stronger correlation to deformity, spasticity and motor control compared to the WeeFIM.</p> <p>Conclusion</p> <p>The degree of deformity, spasticity, sensory deficit, and motor control affected the hand function of a cerebral palsy patient significantly. The MAULF and FHGT more accurately represents hand function deficit in cerebral palsy patients.</p

Prediction model for short-term mortality after palliative radiotherapy for patients having advanced cancer: a cohort study from routine electronic medical data.

We developed a predictive score system for 30-day mortality after palliative radiotherapy by using predictors from routine electronic medical record. Patients with metastatic cancer receiving first course palliative radiotherapy from 1 July, 2007 to 31 December, 2017 were identified. 30-day mortality odds ratios and probabilities of the death predictive score were obtained using multivariable logistic regression model. Overall, 5,795 patients participated. Median follow-up was 39.6 months (range, 24.5-69.3) for all surviving patients. 5,290 patients died over a median 110 days, of whom 995 (17.2%) died within 30 days of radiotherapy commencement. The most important mortality predictors were primary lung cancer (odds ratio: 1.73, 95% confidence interval: 1.47-2.04) and log peripheral blood neutrophil lymphocyte ratio (odds ratio: 1.71, 95% confidence interval: 1.52-1.92). The developed predictive scoring system had 10 predictor variables and 20 points. The cross-validated area under curve was 0.81 (95% confidence interval: 0.79-0.82). The calibration suggested a reasonably good fit for the model (likelihood-ratio statistic: 2.81, P = 0.094), providing an accurate prediction for almost all 30-day mortality probabilities. The predictive scoring system accurately predicted 30-day mortality among patients with stage IV cancer. Oncologists may use this to tailor palliative therapy for patients

Genome-Wide Association Study of Hepatocellular Carcinoma in Southern Chinese Patients with Chronic Hepatitis B Virus Infection

One of the most relevant risk factors for hepatocellular carcinoma (HCC) development is chronic hepatitis B virus (HBV) infection, but only a fraction of chronic HBV carriers develop HCC, indicating that complex interactions among viral, environmental and genetic factors lead to HCC in HBV-infected patients. So far, host genetic factors have incompletely been characterized. Therefore, we performed a genome-wide association (GWA) study in a Southern Chinese cohort consisting of 95 HBV-infected HCC patients (cases) and 97 HBV-infected patients without HCC (controls) using the Illumina Human610-Quad BeadChips. The top single nucleotide polymorphisms (SNPs) were then validated in an independent cohort of 500 cases and 728 controls. 4 SNPs (rs12682266, rs7821974, rs2275959, rs1573266) at chromosome 8p12 showed consistent association in both the GWA and replication phases (ORcombined = 1.31–1.39; pcombined = 2.71×10−5–5.19×10−4; PARcombined = 26–31%). We found a 2.3-kb expressed sequence tag (EST) in the region using in-silico data mining and verified the existence of the full-length EST experimentally. The expression level of the EST was significantly reduced in human HCC tumors in comparison to the corresponding non-tumorous liver tissues (P<0.001). Results from sequence analysis and in-vitro protein translation study suggest that the transcript might function as a long non-coding RNA. In summary, our study suggests that variations at chromosome 8p12 may promote HCC in patients with HBV. Further functional studies of this region may help understand HBV-associated hepatocarcinogenesis

Clinical Efficacy of a 24-months Course of Lamivudine Therapy in Patients with HBeAg Negative Chronic Hepatitis B: A Long-term Prospective Study

The optimal duration of oral nucleos(t)ide analogue therapy for HBeAg negative chronic hepatitis B (CHB) has not been defined. The aim of this study was to investigate the clinical efficacy of 24-months course of lamivudine therapy in patients with HBeAg negative CHB in Korea. A total of 50 Korean patients with HBeAg negative CHB were prospectively enrolled. The patients received 100 mg/day of lamivudine orally for 24 months. Patients who showed complete response at 24 months to lamivudine therapy stopped treatment, and regular follow-up was done thereafter. The mean follow-up duration after cessation of therapy was 40.8±22.7 (range 12-96) months. The complete response rate at months 12 and 24 were 86.0% (43/50) and 86.0% (43/50), respectively, and the clinical breakthrough at months 12 and 24 were 4.0% (2/50) and 14.0% (7/50), respectively. The expected durability of responses at months 12, 24, and 36 after cessation of lamivudine therapy in 43 complete responders was 79.1%, 64.0%, and 56.9%, respectively. In conclusion, a 24-months course of lamivudine therapy shows high end-treatment response rate and substantial durability of initial response after cessation of therapy in HBeAg negative CHB patients in Korea

The Spill-Over Impact of the Novel Coronavirus-19 Pandemic on Medical Care and Disease Outcomes in Non-communicable Diseases: A Narrative Review

OBJECTIVES: The coronavirus-19 (COVID-19) pandemic has claimed more than 5 million lives worldwide by November 2021. Implementation of lockdown measures, reallocation of medical resources, compounded by the reluctance to seek help, makes it exceptionally challenging for people with non-communicable diseases (NCD) to manage their diseases. This review evaluates the spill-over impact of the COVID-19 pandemic on people with NCDs including cardiovascular diseases, cancer, diabetes mellitus, chronic respiratory disease, chronic kidney disease, dementia, mental health disorders, and musculoskeletal disorders. METHODS: Literature published in English was identified from PubMed and medRxiv from January 1, 2019 to November 30, 2020. A total of 119 articles were selected from 6,546 publications found. RESULTS: The reduction of in-person care, screening procedures, delays in diagnosis, treatment, and social distancing policies have unanimously led to undesirable impacts on both physical and psychological health of NCD patients. This is projected to contribute to more excess deaths in the future. CONCLUSION: The spill-over impact of COVID-19 on patients with NCD is just beginning to unravel, extra efforts must be taken for planning the resumption of NCD healthcare services post-pandemic

Efficacy, safety and immunogenicity of a human rotavirus vaccine (RIX4414) in Hong Kong children up to three years of age: A randomized, controlled trial

AbstractBackgroundA phase III, double-blind, randomized, controlled trial was conducted in Hong Kong to evaluate the efficacy, safety and immunogenicity of a human rotavirus vaccine, RIX4414 (Rotarix™) against severe rotavirus gastroenteritis in children up to three years of age.MethodsHealthy infants aged 6–12 weeks were enrolled between 08-December-2003 and 31-August-2005 and received two oral doses of either RIX4414 vaccine (N=1513) or placebo (N=1512) given 2 months apart. Vaccine efficacy was assessed from two weeks post-Dose 2 until the children were two and three years of age. Anti-rotavirus IgA seroconversion rate was calculated pre-vaccination and 1–2 months post-Dose 2 using ELISA (cut-off=20U/mL) for 100 infants. Safety was assessed until the children were two years of age; serious adverse events (SAEs) were recorded throughout the study period.ResultsIn children aged two and three years of life, vaccine efficacy against severe rotavirus gastroenteritis was 95.6% (95% CI: 73.1%–99.9%) and 96.1% (95% CI: 76.5%–99.9%), respectively. The seroconversion rate 1–2 months after the second dose of RIX4414 was 97.5% (95% CI: 86.8%–99.9%). At least one SAE was recorded in 439 and 477 infants who were administered RIX4414 and placebo, respectively (p-value=0.130). Six intussusception cases were reported (RIX4414=4; placebo=2) and none was assessed to be vaccine-related.ConclusionRIX4414 was efficacious, immunogenic and safe in the prevention of rotavirus gastroenteritis for at least two years post-vaccination in Hong Kong children

Epidemiology of Acute Myocarditis/Pericarditis in Hong Kong Adolescents Following Comirnaty Vaccination

BACKGROUND: Age-specific incidence of acute myocarditis/pericarditis in adolescents following Comirnaty vaccination in Asia is lacking. This study aimed to study the clinical characteristics and incidence of acute myocarditis/pericarditis among Hong Kong adolescents following Comirnaty vaccination. METHODS: This is a population cohort study in Hong Kong that monitored adverse events following immunization through a pharmacovigilance system for COVID-19 vaccines. All adolescents aged between 12 and 17 years following Comirnaty vaccination were monitored under the COVID-19 vaccine Adverse Event Response and Evaluation Programme. The clinical characteristics and overall incidence of acute myocarditis/pericarditis in adolescents following Comirnaty vaccination were analysed. RESULTS: Between 14 June 2021 and 4 September 2021, 33 Chinese adolescents who developed acute myocarditis/pericarditis following Comirnaty vaccination were identified. 29 (87.88%) were males and 4 (12.12%) were females, with a median age of 15.25 years. 27 (81.82%) and 6 (18.18%) cases developed acute myocarditis/pericarditis after receiving the second and first dose, respectively. All cases are mild and required only conservative management.The overall incidence of acute myocarditis/pericarditis was 18.52 (95% Confidence Interval [CI], 11.67-29.01) per 100,000 persons vaccinated. The incidence after the first and second doses were 3.37 (95%CI 1.12-9.51) and 21.22 (95%CI 13.78-32.28 per 100,000 persons vaccinated, respectively. Among male adolescents, the incidence after the first and second doses were 5.57 (95% CI 2.38-12.53) and 37.32 (95% CI 26.98-51.25) per 100,000 persons vaccinated. CONCLUSIONS: There is a significant increase in the risk of acute myocarditis/pericarditis following Comirnaty vaccination among Chinese male adolescents, especially after the second dose

IDDF2020-ABS-0060 Impact of prior tenofovir disoproxil fumarate (TDF) treatment duration on tenofovir alafenamide (TAF) safety profile in virally suppressed chronic HBV patients switched from TDF to TAF

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