Mechanism of action and resistant profile of anti-HIV-1 coumarin derivatives

Dicamphanoyl khellactone (DCK) is a coumarin derivative that can potently inhibit HIV-1 replication. DCK does not inhibit RNA-dependent DNA synthesis. However, an HIV reverse transcriptase (RT) inhibitor-resistant strain, HIV-1/RTMDR1, is resistant to DCK. Thus, it is possible that HIV-1 RT is the target of DCK. To test this possibility, DCK-resistant viruses were selected in the presence of DCK. Our results indicate that a single amino acid mutation, E138K in HIV-1 RT, is sufficient to confer DCK resistance. Interestingly, a DCK derivative, 3'R,4'R-Di-O-(-)-camphanoyl-2-ethyl-2',2'-dimethyldihydropyrano[2,3-f]chromo ne (DCP8), is effective against HIV-1/RTMDR1. However, the DCK-escape virus carrying the E138K mutation remains resistant to DCP8. Since DCK did not inhibit the RNA-dependent DNA polymerase activity of HIV-1 RT when using poly-rA or poly-rC as template, we evaluated the effect of DCK on the DNA-dependent DNA polymerase activity of HIV-1 RT. Our results indicate that DCK can inhibit the DNA-dependent DNA polymerase activity of HIV-1 RT. In conclusion, DCK is a unique HIV-1 RT inhibitor that inhibits the DNA-dependent DNA polymerase activity. In contrast, DCK did not significantly affect the RNA-dependent DNA polymerase activity when poly-rA or poly-rC was used as templates. An E138K mutation in the non-nucleoside RT inhibitors (NNRTIs) binding pocket of HIV-1 RT confers resistance to DCK and its chromone derivative, DCP8

The Influence of Online Sports Games on Somatosensory Experiences and Sports Attitudes of Undergraduate Students in Taiwan

The purpose of this study was to explore the relationship among the somatosensory experience, perceived experience value, and sports attitude towards online sports games in undergraduate students in Taiwan. The results of this study show that the sensory, emotional, and relational dimensions of the somatosensory experience can effectively predict perceived experience value and sports attitudes, and the hedonic value dimension of perceived experience value can effectively predict the sports attitude. The results and suggestions can be used as references for relevant units that are involved in university curriculum planning, for curriculum design, and to manage promoting student participation in sports

Model Extraction Attack against Self-supervised Speech Models

Self-supervised learning (SSL) speech models generate meaningful representations of given clips and achieve incredible performance across various downstream tasks. Model extraction attack (MEA) often refers to an adversary stealing the functionality of the victim model with only query access. In this work, we study the MEA problem against SSL speech model with a small number of queries. We propose a two-stage framework to extract the model. In the first stage, SSL is conducted on the large-scale unlabeled corpus to pre-train a small speech model. Secondly, we actively sample a small portion of clips from the unlabeled corpus and query the target model with these clips to acquire their representations as labels for the small model's second-stage training. Experiment results show that our sampling methods can effectively extract the target model without knowing any information about its model architecture

The association between diabetes-related distress and fear of hypoglycaemia in patients with type 2 diabetes mellitus: A cross-sectional descriptive study

Aim: The study aimed to explore the association between diabetes-related distress as a dependent variable and fear of hypoglycaemia as a independent variable in Chinese individuals with type 2 diabetes, which can provide a basis for the development of effective nursing interventions. Design: A cross-sectional descriptive study. Methods: Pre-piloted scales were used to determine whether they experienced fear of hypoglycaemia and whether this impacted upon their management of the disease. From June–October 2019, participants were asked to complete the “hypoglycaemia fear survey” and “diabetes distress scales” to assess levels of fear and distress. Stepwise multivariate regression analysis was applied to reveal relationship between distress as a dependent variable and fear as a independent variable. Covariates included demographic, clinical or lifestyle factors. Results: A total of 258 participants were recruited for the survey, and they were characterized by little or no distress (39.53%), moderate distress (45.35%) and high distress (15.12%). The prevalence of moderate to severe distress in patients was 60.47%. Increased diabetes-related distress was strongly correlated with increased fear of hypoglycaemia and closely associated with the scores of the worry and behaviour subscales. These results indicated that 62.3% of diabetes-related distress may be explained by fear of hypoglycaemia. Conclusion: Increased diabetes-related distress is associated with increased fear of hypoglycaemia in individuals with type 2 diabetes

Positive spiritual climate supports transformational leadership as means to reduce nursing burnout and intent to leave

AimTo explore the relationship between spiritual climate and transformational leadership, and examine their impact on nurses perceived emotional exhaustion and intentions to quit.BackgroundTransformational leadership is known to have a significant positive effect on work environment and job satisfaction. Additionally, promoting spiritual climate amongst staff can benefit workers by increasing self‐worth. The relationship between the two is unknown.MethodsNurse clinicians from 2 sites in the Jiangsu Province of China completed self‐report questionnaires based on spiritual climate, emotional exhaustion, clinical leadership and Turnover Intention Scales. Mediation analysis was applied to evaluate impact of spiritual climate.ResultsPerceived positive spirituality amongst nurse clinicians reinforces transformational leadership to reduce emotional exhaustion (indirect effect of −0.089, p < .01). Burnout and intention to leave showed significantly positive correlation with lower levels of perceived spirituality (r = .545, p < .01).ConclusionTransformational leadership in the workplace can reduce nurses' burnout, and a positive spiritual climate increases meaningfulness in their work. This may help in nurse retention.Implications for Nursing ManagementHealth care leaders must look beyond transformational leadership to maintain a positive and supportive clinical climate, and this may involve acknowledgement of nurses' spiritual needs

The experience and attitude of TMU faculty and researchers toward predatory journals and research productivity

A questionnaire&nbsp;related to&nbsp;journal submission was sent to researchers for a 2-week period to investigate the submission status as well as the problems faced by Taipei Medical University faculties and researchers. This study has two major findings including the Experience of predatory journal and Calculations of academic performance point and discuss about users’ cognition and their needs from the library and the university, as well as the library policy and services related to predatory journals. It is authors’ hope that the research results can serve as reference for other medical libraries planning to provide relevant services

High serum levels of procalcitonin and soluble TREM-1 correlated with poor prognosis in pulmonary tuberculosis

SummaryObjectivesComparisons of procalcitonin (PCT), C-reactive protein (CRP), and soluble triggering receptor expressed on myeloid cells-1 (sTREM-1) would expand our knowledge of which biomarker is the best predictor for outcomes of patients with pulmonary tuberculosis (PTB).MethodsWe prospectively enrolled 243 PTB patients, in whom PCT, CRP, and sTREM-1 measurement were performed to evaluate their prognostic value for 6-month mortality.ResultsSerum PCT, CRP, and sTREM-1 levels on diagnosis of PTB were significantly higher in nonsurvivors (2.22 ± 6.22 vs. 0.13 ± 0.31 ng/mL, P = 0.043; 42.1 ± 59.4 vs. 12.5 ± 29.1 mg/L, P = 0.004; 332 ± 362 vs. 128 ± 98 pg/mL, P = 0.001, respectively) as compared with 6-month survivors. In multivariate Cox regression analysis, PCT ≧0.5 ng/mL (hazard ratio 4.13, 95% CI, 1.99–8.58) and sTREM-1 ≧129 pg/mL (hazard ratio 3.39, 95% CI, 1.52–7.58) remained independent mortality predictors. Serum PCT and sTREM-1 levels above the cutoffs were also associated with the presence of disseminated tuberculosis.ConclusionsAmong PTB patients, higher PCT, CRP, and sTREM-1 levels are observed in nonsurvivors than in 6-month survivors. Serum levels of PCT and sTREM-1 over the cutoffs are independently associated with a poor outcome. In addition, higher PCT and sTREM-1 levels would raise the clinical suspicion of disseminated tuberculosis

Trends and predictors of changes in pulmonary function after treatment for pulmonary tuberculosis

OBJECTIVES: The present study aimed to investigate the trends in changes in pulmonary function and the risk factors for pulmonary function deterioration in patients with pulmonary tuberculosis after completing treatment. INTRODUCTION: Patients usually have pulmonary function abnormalities after completing treatment for pulmonary tuberculosis. The time course for changes in pulmonary function and the risk factors for deterioration have not been well studied. METHODS: A total of 115 patients with 162 pulmonary function results were analyzed. We retrieved demographic and clinical data, radiographic scores, bacteriological data, and pulmonary function data. A generalized additive model with a locally weighted scatterplot smoothing technique was used to evaluate the trends in changes in pulmonary function. A generalized estimating equation model was used to determine the risk factors associated with deterioration of pulmonary function. RESULTS: The median interval between the end of anti-tuberculosis treatment and the pulmonary function test was 16 months (range: 0 to 112 months). The nadir of pulmonary function occurred approximately 18 months after the completion of the treatment. The risk factors associated with pulmonary function deterioration included smear-positive disease, extensive pulmonary involvement prior to anti-tuberculosis treatment, prolonged anti-tuberculosis treatment, and reduced radiographic improvement after treatment. CONCLUSIONS: After the completion of anti-tuberculosis TB treatment, several risk factors predicted pulmonary function deterioration. For patients with significant respiratory symptoms and multiple risk factors, the pulmonary function test should be followed up to monitor the progression of functional impairment, especially within the first 18 months after the completion of anti-tuberculosis treatment