307 research outputs found

    Kaedah pemilihan media pengajaran komponen sastera (KOMSAS) oleh guru cemerlang Bahasa Melayu

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    Pemilihan media pengajaran merupakan satu elemen atau langkah wajib yang berperanan penting dalam reka bentuk pengajaran. Media pengajaran yang dipilih akan menentukan keberkesanan dan impak proses pengajaran dan pembelajaran. Justeru, kajian ini dijalankan untuk meneroka kaedah pemilihan media pengajaran komponen sastera (KOMSAS) oleh guru cemerlang Bahasa Melayu. Kaedah pemilihan akan diteroka dari aspek jenis media pengajaran dan faktor pemilihan. Kajian ini dijalankan secara kualitatif dengan mengumpul data melalui tiga sumber iaitu temu bual, pemerhatian, dan analisis dokumen. Dua orang guru cemerlang Bahasa Melayu yang mempunyai pengalaman mengajar mata pelajaran Bahasa Melayu lebih daripada 30 tahun telah dipilih sebagai peserta kajian ini. Lapan sesi temu bual dijalankan dalam bentuk separa berstruktur. Data temu bual disokong dengan pemerhatian terhadap proses pengajaran di dalam kelas, jenis media pengajaran yang digunakan oleh guru serta hasil kerja pelajar. Dapatan menunjukkan bahawa guru cemerlang memilih dan mengintegrasikan pelbagai jenis media iaitu bahan cetak, manusia, aktiviti, dan bahan grafik dalam pengajaran KOMSAS. Kedua-dua guru cemerlang tersebut telah mengambil kira faktor ketersediaan, tahap pengetahuan pelajar, kemahiran guru, dan objektif pembelajaran sebelum memilih media pengajaran

    Direct arene trifluoromethylation enabled by promiscuous activity of fungal laccase

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    Simple non-invasive scoring systems and histological scores in predicting mortality in patients with non-alcoholic fatty liver disease: A systematic review and meta-analysis

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    [Background and Aim] There is debate among the hepatology community regarding the simple non-invasive scoring systems and histological scores (even it was developed for histological classification) in predicting clinical outcomes in patients with non-alcoholic fatty liver disease (NAFLD). This study aimed to determine whether the presence of simple non-invasive scoring systems and histological scores could predict all-cause mortality, liver-related mortality, and liver disease decompensation (liver failure, cirrhosis, hepatocellular carcinoma, or decompensated liver disease).[Methods] The pooled hazard ratio of prognostic factors and incidence rate per 1000 person-years in patients with NAFLD was calculated and further adjusted by two different models of handling the duplicated data.[Results] A total of 19 longitudinal studies were included. Most simple non-invasive scoring systems (Fibrosis-4 Score, BARD, and aspartate aminotransferase-to-platelet ratio index ) and histological scores (NAFLD activity score, Brunt, and "steatosis, activity, and fibrosis" ) failed in predicting mortality, and only the NAFLD fibrosis score > 0.676 showed prognostic ability to all-cause mortality (four studies, 7564 patients, 118 352 person-years followed up, pooled hazard ratio 1.44, 95% confidence interval [CI] 1.05–1.96). The incidence rate per 1000 person-years of all-cause mortality, liver-related mortality, cardiovascular-related mortality, and liver disease decompensation resulted in a pooled incidence rate per 1000 person-years of 22.65 (14 studies, 95% CI 9.62–53.31), 3.19 (7 studies, 95% CI 1.14–8.93), 6.02 (6 studies, 95% CI 4.69–7.74), and 11.46 (4 studies, 95% CI 5.33–24.63), respectively.[Conclusion] Non-alcoholic fatty liver disease fibrosis score showed promising prognostic value to all-cause mortality. Most present simple non-invasive scoring systems and histological scores failed to predict clinical outcomes.Peer reviewe

    C-Terminal Binding Protein 2 Is a Novel Tumor Suppressor Targeting the Myc-Irf4 axis in Multiple Myeloma

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    Multiple myeloma (MM) cells are addicted to MYC and its direct transactivation targets IRF4 for proliferation and survival. MYC and IRF4 are still considered undruggable, as most small-molecule inhibitors suffer from low potency, suboptimal pharmacokinetic properties, and undesirable off-target effects. Indirect inhibition of MYC/IRF4 emerges as a therapeutic vulnerability in MM. Here, we uncovered an unappreciated tumor-suppressive role of C-terminal binding protein 2 (CTBP2) in MM via strong inhibition of the MYC-IRF4 axis. In contrast to epithelial cancers, CTBP2 is frequently downregulated in MM, in association with shortened survival, hyperproliferative features, and adverse clinical outcomes. Restoration of CTBP2 exhibited potent antitumor effects against MM in vitro and in vivo, with marked repression of the MYC-IRF4 network genes. Mechanistically, CTBP2 impeded the transcription of MYC and IRF4 by histone H3 lysine 27 deacetylation (H3K27ac) and indirectly via activation of the MYC repressor IFIT3. In addition, activation of the interferon gene signature by CTBP2 suggested its concomitant immunomodulatory role in MM. Epigenetic studies have revealed the contribution of polycomb-mediated silencing and DNA methylation to CTBP2 inactivation in MM. Notably, inhibitors of Enhance of zeste homolog 2, histone deacetylase, and DNA methyltransferase, currently under evaluation in clinical trials, were effective in restoring CTBP2 expression in MM. Our findings indicated that the loss of CTBP2 plays an essential role in myelomagenesis and deciphers an additional mechanistic link to MYC-IRF4 dysregulation in MM. We envision that the identification of novel critical regulators will facilitate the development of selective and effective approaches for treating this MYC/IRF4-addicted malignancy

    Genome wide analysis of gene expression changes in skin from patients with type 2 diabetes

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    Non-healing chronic ulcers are a serious complication of diabetes and are a major healthcare problem. While a host of treatments have been explored to heal or prevent these ulcers from forming, these treatments have not been found to be consistently effective in clinical trials. An understanding of the changes in gene expression in the skin of diabetic patients may provide insight into the processes and mechanisms that precede the formation of non-healing ulcers. In this study, we investigated genome wide changes in gene expression in skin between patients with type 2 diabetes and non-diabetic patients using next generation sequencing. We compared the gene expression in skin samples taken from 27 patients (13 with type 2 diabetes and 14 non-diabetic). This information may be useful in identifying the causal factors and potential therapeutic targets for the prevention and treatment of diabetic related diseases

    Effectiveness of post-COVID-19 primary care attendance in improving survival in very old patients with multimorbidity: A territory-wide target trial emulation

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    Objectives:  Older individuals with multimorbidity are at an elevated risk of infection and complications from COVID-19. Effectiveness of post-COVID-19 interventions or care models in reducing subsequent adverse outcomes in these individuals have rarely been examined. This study aims to examine the effectiveness of attending general outpatient within 30 days after discharge from COVID-19 on 1-year survival among older adults aged 85 years or above with multimorbidity.  Design: Retrospective cohort study emulating a randomised target trial using electronic health records. Setting We used data from the Hospital Authority and the Department of Health in Hong Kong, which provided comprehensive electronic health records, COVID-19 confirmed case data, population-based vaccination records and other individual characteristics for the study.  Participants: Adults aged 85 years or above with multimorbidity who were discharged after hospitalisation for COVID-19 between January 2020 and August 2022. Interventions Attending a general outpatient within 30 days of last COVID-19 discharge defined the exposure, compared to no outpatient visit. Main outcome measures Primary outcome was all-cause mortality within one year. Secondary outcomes included mortality from respiratory, cardiovascular and cancer causes.  Results: A total of 6183 eligible COVID-19 survivors were included in the analysis. The all-cause mortality rate following COVID-19 hospitalisation was lower in the general outpatient visit group (17.1 deaths per 100 person-year) compared with non-visit group (42.8 deaths per 100 person-year). After adjustment, primary care consultations within 30 days after discharge were associated with a significantly greater 1-year survival (difference in 1-year survival: 11.2%, 95% CI 8.1% to 14.4%). We also observed significantly better survival from respiratory diseases in the general outpatient visit group (difference in 1-year survival: 6.3%, 95% CI 3.5% to 8.9%). In a sensitivity analysis for different grace period lengths, we found that the earlier participants had a general outpatient visit after COVID-19 discharge, the better the survival.  Conclusions: Timely primary care consultations after COVID-19 hospitalisation may improve survival following COVID-19 hospitalisation among older adults aged 85 or above with multimorbidity. Expanding primary care services and implementing follow-up mechanisms are crucial to support this vulnerable population's recovery and well-being

    Biophysical and nutritional combination treatment for myosteatosis in patients with sarcopenia: a study protocol for single-blinded randomised controlled trial

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    Introduction Sarcopenia is characterised by age-related loss of skeletal muscle and function and is associated with risks of adverse outcomes. The prevalence of sarcopenia increases due to ageing population and effective interventions is in need. Previous studies showed that β-hydroxy β-methylbutyrate (HMB) supplement and vibration treatment (VT) enhanced muscle quality, while the coapplication of the two interventions had further improved muscle mass and function in sarcopenic mice model. This study aims to investigate the efficacy of this combination treatment in combating sarcopenia in older people. The findings of this study will demonstrate the effect of combination treatment as an alternative for managing sarcopenia. Methods and analysis In this single-blinded randomised controlled trial, subjects will be screened based on the Asian Working Group for Sarcopenia (AWGS) 2019 definition. 200 subjects who are aged 65 or above and identified sarcopenic according to the AWGS algorithm will be recruited. They will be randomised to one of the following four groups: (1) Control+ONS; (2) HMB+ONS; (3) VT+ONS and (4) HMB+VT + ONS, where ONS stands for oral nutritional supplement. ONS will be taken in the form of protein formular once/day; HMB supplements will be 3 g/day; VT (35 Hz, 0.3 g, where g=gravitational acceleration) will be received for 20 mins/day and at least 3 days/week. The primary outcome assessments are muscle strength and function. Subjects will be assessed at baseline, 3-month and 6-month post treatment. Ethics and dissemination This study was approved by Joint CUHK-NTEC (The Chinese University of Hong Kong and New Territories East Cluster) Clinical Research Management Office (Ref: CRE-2022.223-T) and conformed to the Declaration of Helsinki. Trial results will be published in peer-reviewed journals and disseminated at academic conferences

    Long-Baseline Neutrino Facility (LBNF) and Deep Underground Neutrino Experiment (DUNE) Conceptual Design Report Volume 2: The Physics Program for DUNE at LBNF

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    The Physics Program for the Deep Underground Neutrino Experiment (DUNE) at the Fermilab Long-Baseline Neutrino Facility (LBNF) is described
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