Cardiopulmonary resuscitation (CPR) training and its quality are critical in improving the survival rate of cardiac arrest. This randomized controlled study investigated the efficacy of a newly ...developed CPR training program for the public in a Taiwanese setting. A total of 832 adults were randomized to either a traditional or blended (18-minute e-learning plus 30-minute hands-on) compression-only CPR training program. The primary outcome was compression depth. Secondary outcomes included CPR knowledge test, practical test, quality of CPR performance, and skill retention. The mean compression depth was 5.21 cm and 5.24 cm in the blended and traditional groups, respectively. The mean difference in compression depth between groups was -0.04 (95% confidence interval -0.13 to infinity), demonstrating that the blended CPR training program was non-inferior to the traditional CPR training program in compression depth after initial training. Secondary outcome results were comparable between groups. Although the mean compression depth and rate were guideline-compliant, only half of the compressions were delivered with adequate depth and rate in both groups. CPR knowledge and skill retained similarly in both groups at 6 and 12 months after training. The blended CPR training program was non-inferior to the traditional CPR training program. However, there is still room for improvement in optimizing initial skill performance as well as skill retention. Clinical Trial Registration: NCT03586752; www.clinicaltrial.gov.
Abstract
Testing and treatment of tuberculosis infection (TBI) are recommended for people living with HIV (PLWH). We aimed to evaluate the care cascade of TBI treatment among PLWH in the era of ...antiretroviral therapy (ART) scale-up. This retrospective study included adult PLWH undergoing interferon-gamma release assay (IGRA)-based TBI screening during 2019–2021. PLWH testing IGRA-positive were advised to receive directly-observed therapy for TBI after active TB disease was excluded. The care cascade was evaluated to identify barriers to TBI management. Among 7951 PLWH with a median age of 38 years and CD4 count of 616 cells/mm
3
, 420 (5.3%) tested positive and 38 (0.5%) indeterminate for IGRA. The TBI treatment initiation rate was 73.6% (309/420) and the completion rate was 91.9% (284/309). More than 80% of PLWH concurrently received short-course rifapentine-based regimens and integrase strand transfer inhibitor (InSTI)-containing ART. The main barrier to treatment initiation was physicians’ concerns and patients’ refusal (85.6%). The factors associated with treatment non-completion were older age, female, anti-HCV positivity, and higher plasma HIV RNA. Our observation of a high TBI completion rate among PLWH is mainly related to the introduction of short-course rifapentine-based regimens in the InSTI era, which can be the strategy to improve TBI treatment uptake.
ObjectivesTo evaluate whether nephrotic syndrome (NS) and further corticosteroid (CS) use increase the risk of osteoporosis in Asian population during the period January 2000–December ...2010.DesignNationwide population-based retrospective cohort study.SettingAll healthcare facilities in Taiwan.ParticipantsA total of 28 772 individuals were enrolled.Interventions26 614 individuals with newly diagnosed NS between 2000 and 2010 were identified and included in out study. 26 614 individuals with no NS diagnosis prior to the index date were age matched as controls. Diagnosis of osteoporosis prior to the diagnosis of NS or the same index date was identified, age, sex and NS-associated comorbidities were adjusted.Primary outcome measureTo identify risk differences in developing osteoporosis among patients with a medical history of NS.ResultsAfter adjusting for covariates, osteoporosis risk was found to be 3.279 times greater in the NS cohort than in the non-NS cohort, when measured over 11 years after NS diagnosis. Stratification revealed that age older than 18 years, congestive heart failure, hyperlipidaemia, chronic kidney disease, liver cirrhosis and NS-related disease including diabetes mellitus, hepatitis B infection, hepatitis C infection, lymphoma and hypothyroidism, increased the risk of osteoporosis in the NS cohort, compared with the non-NS cohort. Additionally, osteoporosis risk was significantly higher in NS patients with CS use (adjusted HR (aHR)=3.397). The risk of osteoporosis in NS patients was positively associated with risk of hip and vertebral fracture (aHR=2.130 and 2.268, respectively). A significant association exists between NS and subsequent risk for osteoporosis.ConclusionNS patients, particularly those treated with CS, should be evaluated for subsequent risk of osteoporosis.
The Bitcoin exchange rate (BER) is influenced by many variables such as human speculation and policies and, thus, is dependent on the financial system. The fluctuation of BER submitted has been ...extensively investigated. However, the correlation analysis of the short- and long-term effects by indicators of online sentiment is unexplored. Therefore, this study establishes a VAR model for BER which provides a framework to the Google search volume index (SVI), the investor fear gauge (VIX), and the S&P500 Index. The findings of the analysis suggest that BER and Google SVI have a Granger causality feedback relationship in both the short- and long-term co-integration equilibrium, and the VIX is significantly related to BER in the long-term co-integration.
This study evaluates the performance of the Taiwan Earth System Model version 1 (TaiESM1) in simulating the observed climate variability in the historical simulation of the Coupled Model ...Intercomparison Phase 6 (CMIP6). TaiESM1 is developed on the basis of the Community Earth System Model version 1.2.2, with the inclusion of several new physical schemes and improvements in the atmosphere model. The new additions include an improved triggering function in the cumulus convection scheme, a revised distribution‐based formula in the cloud fraction scheme, a new aerosol scheme, and a unique scheme for three‐dimensional surface absorption of shortwave radiation that accounts for the influence of complex terrains. In contrast to the majority of model evaluation processes, which focus mainly on the climatological mean, this evaluation focuses on climate variability parameters, including the diurnal rainfall cycle, precipitation extremes, synoptic eddy activity, intraseasonal fluctuation, monsoon evolution, and interannual and multidecadal atmospheric and oceanic teleconnection patterns. A series of intercomparisons between the simulations of TaiESM1 and CMIP6 models and observations indicate that TaiESM1, a participating model in CMIP6, can realistically simulate the observed climate variability at various time scales and are among the leading CMIP6 models in terms of many key climate features.
Plain Language Summary
Earth System Models are important tools for understanding how earth system changes and providing information for mitigation and adaption facing future climate changes. Taiwan Earth System Model version 1 (TaiESM1) is developed in the Research Center for Environmental Changes, Academia Sinica, Taiwan, with the goal to join the effort of the international model intercomparison—the Coupled Model Intercomparison Phase 6 (CMIP6). Based on the Community Earth System Model version 1, key improvements of TaiESM1 are in the representation of how raining systems starts, how cloud covers shade, how aerosols form and dissipate, and how topography reflects sunlight. We compare TaiESM1s performance with observations and other CMIP6 models to understand TaiESM1’s capability in simulating climate systems and future climate changes. We especially focus on evaluating the climate variability on a wide range of time scales, i.e., how climate systems change on those of within one day, day‐to‐day, seasonal, year‐to‐year, and decades‐to‐decades. Our analysis shows that TaiESM1 can realistically represent the observed climate variability and would help to expand our understandings of the earth system with the global scientific community and society as a whole.
Key Points
Climate variability in the historical simulation of Taiwan Earth System Model version 1 (TaiESM1) is evaluated
While still subject to several common biases, TaiESM1's performance of mean climate states is among the leading CMIP6 models
TaiESM1 is capable of realistically simulating key climate features, including the diurnal rainfall, monsoon evolution, and teleconnection
Evidence that circular RNAs (circRNAs) serve as protein template is accumulating. However, how the cap-independent translation is controlled remains largely uncharacterized. Here we show that the ...presence of intron and thus splicing promote cap-independent translation. By acquiring the exon junction complex (EJC) after splicing, the interaction between circRNA and ribosomes was promoted, thereby facilitating translation. Prevention of splicing by treatment with spliceosome inhibitor or mutating splicing signal hindered cap-independent translation of circRNA. Moreover, EJC-tethering using Cas13 technology reconstituted EJC-dependent circRNA translation. Finally, the level of a coding circRNA from succinate dehydrogenase assembly factor 2 (circSDHAF2) was found to be elevated in the tumorous tissues from patients with colorectal cancer (CRC) and shown to be critical in tumorigenesis of CRC in both cell and murine models. These findings reveal that EJC-dependent control of circSDHAF2 translation is involved in the regulation of oncogenic pathways. Implications: EJC-mediated cap-independent translation of circRNA is implicated in the tumorigenesis of colorectal cancer.
The genetic features of the antimicrobial resistance of a multidrug resistant Klebsiella pneumoniae strain harboring bla NDM-1 were investigated to increase our understanding of the evolution of ...NDM-1. The strain, KPX, came from a Taiwanese patient with a hospitalization history in New Delhi. Complete DNA sequencing was performed; and the genes responsible for antimicrobial resistance were systematically examined and isolated by library screening. KPX harbored two resistance plasmids, pKPX-1 and pKPX-2, which are 250-kb and 141-kb in size, respectively, with bla NDM-1 present on pKPX-1. The plasmid pKPX-1 contained genes associated with the IncR and IncF groups, while pKPX-2 belonged to the IncF family. Each plasmid carried multiple antimicrobial resistance genetic determinants. The gene responsible for resistance to carbapenems was found on pKPX-1 and that for resistance to aztreonam was found on pKPX-2. To our surprise, we discovered that bla NDM-1 exists on pKPX-1 as multiple copies in the form of tandem repeats. Amplification of bla NDM-1 was found to occur by duplication of an 8.6-kb unit, with the copy number of the repeat varying from colony to colony. This repeat sequence is identical to that of the pNDM-MAR except for two base substitutions. The copy number of bla NDM-1 of colonies under different conditions was assessed by Southern blotting and quantitative PCR. The bla NDM-1 sequence was maintained in the presence of the antimicrobial selection; however, removal of antimicrobial selection led to the emergence of susceptible bacterial populations with a reduced copy number or even the complete loss of the bla NDM-1 sequence. The dynamic nature of the NDM-1 sequence provides a strong argument for judicious use of the broad-spectrum antimicrobials in order to reduce the development and spread of antimicrobial resistance among pathogens.
In many human cancers, including hepatocellular carcinoma (HCC), high density of infiltrating tumor-associated macrophages (TAM) is associated with poor prognosis. Most TAMs express a M2 phenotype ...subsequently supporting tumor growth. How tumor cells polarize these TAMs to a pro-tumor M2 phenotype is still poorly understood. Our previous studies have revealed that a Toll-like receptor 2 (TLR2)-dependent autophagy triggered by hepatoma-derived factors down-regulates NF-κB p65 and drives M2 macrophage differentiation. However, the underlying mechanisms and potential hepatoma-derived TLR2 ligands are not clear. Here, we provide evidence to reveal that NADPH oxidase 2 (NOX2)-dependent reactive oxygen species (ROS) generation is crucial for HCC-induced autophagy, NF-κB p65 down-regulation and M2 phenotype polarization in primary macrophages. This NOX2-generated ROS production in abolished in TLR2-deficient macrophages. HCC-derived or recombinant high-mobility group box 1 (HMGB1) is able to trigger this TLR2-mediated M2 macrophage polarization. Blockage of HMGB1 and ROS by inhibitors, ethyl pyruvate and N-acetylcysteine amide, respectively, significantly reduces both M2 macrophage accumulation and liver nodule formation in HCC-bearing mice. Our findings uncover a HMGB1/TLR2/NOX2/autophagy axis to trigger M2 macrophage polarization in HCC that can be considered as a novel therapeutic target for treating HCC.
HOPX is a stem cell marker in hair follicles and intestines. It was shown critical for primitive hematopoiesis. We previously showed an association between higher HOPX expression and clinical ...characteristics related to stemness and quiescence of leukemic cells in acute myeloid leukemia (AML) patients. To further explore its physiologic functions in hematopoietic system, we generated a mouse model with hematopoietic cell-specific knockout of Hopx (Hopx−/−). In young Hopx−/− mice, the hematopoietic stem cells (HSC) showed decreased reconstitution ability after serial transplantation. Further transcriptomic study revealed decreased HSC signatures in long-term HSCs from the Hopx−/− mice. At 18 months of age, half of the Hopx−/− mice developed cytopenia and splenomegaly. Bone marrow (BM) from the sick mice showed myeloid hyperplasia with predominant mature neutrophils, and decreased progenitor cells and lymphocytes. These phenotypes suggested critical functions of Hopx in maintaining HSC quiescence. Transcriptomic study of the Hopx−/− marrow cells showed significant downregulation of the Cxcl12-Cxcr4 axis, which is critical for maintenance of HSC quiescence. We next examined the role of Hopx in AML by using the MN1 overexpression murine leukemia model. Mice transplanted with MN1-overexpressed Hopx−/− BM cells developed AML with more aggressive phenotypes compared with those transplanted with MN1-overexpressed Hopx-wild cells. Hopx−/−MN1-overexpressed leukemia cells showed higher proliferation rate and downregulation of Cxcl12 and Cxcr4. Furthermore, in human AML, BM plasma CXCL12 levels were lower in patients with lower HOPX expression. In conclusion, our study highlights the roles of Hopx in maintenance of quiescence of the hematopoietic stem cells through CXCL12 pathway in vivo and provides implication of this protein in normal and malignant hematopoiesis.
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