Diverse cellular functions, including tumor suppressor gene expression, DNA repair, cell proliferation and apoptosis, are regulated by histone acetylation and deacetylation. Histone deacetylases ...(HDACs) are enzymes involved in remodeling of chromatin by deacetylating the lysine residues. They play a pivotal role in epigenetic regulation of gene expression. Dysregulation of HDACs and aberrant chromatin acetylation and deacetylation have been implicated in the pathogenesis of various diseases, including cancer. Histone deacetylases have become a target for the development of drugs for treating cancer because of their major contribution to oncogenic cell transformation. Overexpression of HDACs correlates with tumorigenesis. Previous work showed that inhibition of HDACs results in apoptosis and the inhibition of cell proliferation in multiple cells. A significant number of HDAC inhibitors have been developed in the past decade. These inhibitors have strong anticancer effects in vitro and in vivo, inducing growth arrest, differentiation, and programmed cell death, inhibiting cell migration, invasion, and metastasis, and suppressing angiogenesis. In addition, HDAC‐mediated deacetylation alters the transcriptional activity of nuclear transcription factors, including p53, E2F, c‐Myc, and nuclear factor‐κB, as well as the extracellular signal‐regulated kinase1/2, phosphatidylinositol 3‐kinase, Notch, and Wnt signaling pathways. This review highlights the role of HDACs in cancer pathogenesis and, more importantly, that HDACs are potential novel therapeutic targets.
Aim
This study was designed to investigate the feasibility, acceptability, and preliminary efficacy of a nurse‐led communication intervention among surrogates in the intensive care unit (ICU) guided ...by the COMFORT (Connect; Options; Making meaning; Family caregivers; Openings; Relating; Team) communication model.
Background
As frontline communicators, nurses experience communication difficulties with surrogates who face complex informational and emotional barriers when making decisions for critically ill patients in the ICU. However, research on effective nurse communication focusing on both curative and end‐of‐life (EOL) care is lacking in the literature.
Design
A single‐centre two‐group pretest‐posttest quasi‐experiment.
Method
The total sample included 41 surrogates of adult ventilated patients. Twenty participants were allocated to the intervention group who received a daily 20‐min telephone call with content based on the COMFORT communication model. Twenty‐one participants comprised the control group who received usual care. Participants completed a questionnaire before and after the study measuring satisfaction, anxiety and depression, decisional conflict, and quality of communication. The Transparent Reporting of Evaluations with Nonrandomized Designs (TREND) checklist was followed for nonrandomised controlled trials.
Result
The intervention was feasible, with 19 of 20 surrogates completing the follow‐up surveys, and 48 telephone conversations completed (48% of the planned phone calls). Surrogates' satisfaction was higher in the intervention group than in the control group after adjusting for the selected covariates (25.43 and 24.15, respectively; p = .512). Preliminary efficacy outcomes favouring the intervention included quality of communication with healthcare providers, but not surrogates' perceived depression/anxiety and decisional conflicts.
Conclusion
Implementation of the intervention is feasible, acceptable, and favourable among surrogates to improve quality of communication with healthcare providers in the ICU. Further research is needed to determine whether the intervention could be implemented by nurses to improve surrogates' outcomes in other ICUs.
Microbes are an important part of the vineyard ecosystem, which significantly influence the quality of grapes. Previously, we identified a bud mutant variety (named 'Fengzao') from 'Kyoho' grapes. ...The variation of microbial communities in grape and its bud mutant variety has not been studied yet. So, in this study, with the samples of both 'Fengzao' and 'Kyoho', we conducted high-throughput microbiome sequencing and investigated their microbial communities in different tissues. Obvious differences were observed in the microbial communities between 'Fengzao' and 'Kyoho'. The fruit and the stem are the tissues with relatively higher abundance of microbes, while the leaves contained less microbes. The fruit and the stem of 'Kyoho' and the stem of 'Fengzao' had relatively higher species diversity based on the alpha diversity analysis. Proteobacteria, Enterobacteriaceae and Rhodobacteraceae had significantly high abundance in 'Fengzao'. Firmicutes and Pseudomonas were highly abundant in the stems of 'Kyoho', and family of Spirochaetaceae, Anaplasmataceae, Chlorobiaceae, and Sphingomonadaceae, and genera of Spirochaeta, Sphingomonas, Chlorobaculum and Wolbachia were abundant in the fruits of 'Kyoho'. These identified microbes are main components of the microbial communities, and could be important regulators of grapevine growth and development. This study revealed the differences in the microbial compositions between 'Kyoho' and its bud mutant, and these identified microbes will be significant resources for the future researches on the quality regulation and disease control of grapevines.
Abstract
Objectives
Observational studies have demonstrated associations between gout and hypertension, but whether they are causal remains unclear. Our work aims to assess the causal relationship ...between gout and hypertension.
Methods
We obtained genetic information from the Taiwan Biobank, including 88,347 participants and 686,439 single-nucleotide polymorphisms (SNPs). A novel model of Mendelian randomisation (MR) with coarsened exposures was used to examine the causality between the liability of gout on hypertension and vice versa, using 4 SNPs associated with gout and 10 SNPs associated with hypertension after removal of SNPs associated with measured confounders. The binary exposure (gout/hypertension) can be considered a coarsened approximation of a latent continuous trait. The inverse-variance weighted (IVW) and polygenic risk score (PRS) methods were used to estimate effect size. The MR analysis with coarsened exposures was performed with and without adjustments for covariates.
Results
Of the 88,347 participants, 3253 (3.68%) had gout and 11,948 (13.52%) had hypertension (men, 31.9%; mean age 51.1 SD, 11.1 years). After adjusting to measured confounders, MR analysis with coarsened exposures showed a significant positive causal effect of the liability of gout on hypertension in both the IVW method (relative risk RR, 1.10; 95% confidence interval CI, 1.03–1.19;
p
= 0.0077) and the PRS method (RR, 1.10; 95% CI, 1.02–1.19;
p
= 0.0092). The result of causality was the same before and after involving measured confounders. However, there was no causal effect of the liability of hypertension on gout.
Conclusions
In this study, we showed that the liability of gout has a causal effect on hypertension, but the liability of hypertension does not have a causal effect on gout. Adequate management of gout may reduce the risk of developing hypertension.
Early confirmation of sustained virologic response (SVR) or viral relapse after direct‐acting antivirals (DAAs) for hepatitis C virus (HCV) infection is essential based on public health perspectives, ...particularly for patients with high risk of nonadherence to posttreatment follow‐ups. A total of 1011 patients who achieved end‐of‐treatment virologic response, including 526 receiving fixed‐dose pangenotypic DAAs, and 485 receiving other types of DAAs, who had available off‐treatment weeks 4 and 12 serum HCV RNA data to confirm SVR at off‐treatment week 12 (SVR12) or viral relapse were included. The positive predictive value (PPV) and negative predictive value (NPV) of SVR4 to predict patients with SVR12 or viral relapse were reported. Furthermore, we analyzed the proportion of concordance between SVR12 and SVR24 in 943 patients with available SVR24 data. The PPV and NPV of SVR4 to predict SVR12 were 98.5% (95% confidence interval CI: 98.0–98.9) and 100% (95% CI: 66.4–100) in the entire population. The PPV of SVR4 to predict SVR12 in patients receiving fixed‐dose pangenotypic DAAs was higher than those receiving other types of DAAs (99.8% 95% CI: 98.9–100 vs. 97.1% 95% CI: 96.2–97.8, p < 0.001). The NPVs of SVR4 to predict viral relapse were 100%, regardless of the type of DAAs. Moreover, the concordance between SVR12 and SVR24 was 100%. In conclusion, an off‐treatment week 4 serum HCV RNA testing is sufficient to provide an excellent prediction power of SVR or viral relapse at off‐treatment week 12 among patients with HCV who are treated with fixed‐dose pangenotypic DAAs.
Aims
Amisulpride, a first‐line schizophrenia treatment, has shown large interindividual variability in plasma/serum levels, often outside the reference range (100–320 ng/mL). This study aims to ...clarify the impact of dose, sex, age and related factors for the interpatient variability in amisulpride plasma/serum concentration.
Methods
Both English and Chinese databases were searched from their inception to May 16, 2019, using the terms: amisulpride and (plasma OR serum OR blood OR “drug monitoring” OR concentration). Studies reporting concentrations and either a dose, associated factor, clinical outcome or side effect were included.
Results
Fourteen studies with 1628 participants were eventually included. Eligible articles yielded data on drug concentration and dose, averaging 333.9 (95% confidence interval CI: 294.5–373.3) ng/mL and 636.2 (95% CI: 549.7–722.6) mg/d, respectively. The calculated mean concentration‐to‐dose (C/D) ratio was 0.60 (95% CI: 0.52–0.67) (ng/mL)/mg. Subgroup analysis suggested that female patients on combined lithium‐amisulpride have higher concentration levels and C/D ratios. Age was slight positive associated with C/D ratio while not for plasma level. Smoker patients have high concentration level than nonsmoking patients but not for C/D. Responsive and nonresponsive groups did not differ in concentration and C/D.
Conclusion
Pooled concentration levels of amisulpride were higher than recommended with wide individual variation, especially in older patients, female patients and patients taking amisulpride combined with lithium. The specific therapeutic reference range for amisulpride may require reconstruction, which should consider the influence of age, sex, kidney function, drug–drug interactions, different dose regimens and sampling times in future study.
Comparison of diagnostic accuracy for commercial hepatitis C virus (HCV) genotyping (Abbott RealTime HCV Genotyping II, Roche Cobas Genotyping) and investigational Abbott HCV Genotype plus RUO assays ...designed to discriminate genotype (GT)‐1a, 1b or 6 in cases of ambiguous GT from the Abbott commercial assay remains limited. 743 HCV‐viremic samples were subjected to analysis using Abbott and Roche commercial as well as Abbott HCV Genotype plus RUO assays. Next‐generation sequencing (NGS) targeting core region was employed as the reference standard. Diagnostic accuracy was reported as the number of participants (percentages) along with 95% confidence intervals (CIs). Using NGS, 741 samples (99.7%) yielded valid genotyping results. The diagnostic accuracies were 97.6% (95% CI: 96.1%–98.5%) and 95.3% (95% CI: 93.4%–96.6%) using Abbott and Roche commercial assays (p = 0.0174). Abbott commercial assay accurately diagnosed HCV GT‐6a and 6w, whereas Roche commercial assay accurately diagnosed HCV GT‐6a. Both assays demonstrated low accuracies for HCV GT‐6b, 6e, 6g, and 6n. Abbott HCV Genotype plus RUO assay discriminated 13 of the 14 samples (92.9%; 95% CI: 64.2%–99.6%) that yielded ambiguous GT. Both assays were capable of diagnosing mixed HCV infections when the minor genotype comprised >8.4% of the viral load. The diagnostic performance of commercial HCV genotyping assays is commendable. Abbott assay demonstrated superior performance compared to Roche assay in diagnosing HCV GT‐6. Abbott HCV Genotype plus RUO assay aids in discriminating ambiguous GT. Both commercial assays are proficient in diagnosing mixed HCV infections at a cut‐off viral load of 8.4% in minor genotype.
Electronic cigarettes (e-cigarettes) are relatively new tobacco products that are attracting public attention due to their unique features, especially their many flavor options and their potential as ...an alternative to cigarettes. However, uncertainties remain regarding the determinants and consequences of e-cigarette use because current research on e-cigarettes is made more difficult due to the lack of psychometrically sound instruments that measure e-cigarette related constructs. This systematic review therefore seeks to identify the instruments in the field that are designed to assess various aspects of e-cigarette use or its related constructs and analyze the evidence presented regarding the psychometric properties of the identified instruments.
This systematic review utilized six search engines: PubMed, Medline, CINAHL, PsycINFO, Web of Science, and EMBASE, to identify articles published in the peer-reviewed journals from inception to February 2022 that contained development or validation processes for these instruments.
Eighteen articles describing the development or validation of 22 unique instruments were identified. Beliefs, perceptions, motives, e-cigarette use, and dependence, were the most commonly assessed e-cigarette related constructs. The included studies reported either construct or criterion validity, with 14 studies reporting both. Most studies did not report the content validity; for reliability, most reported internal consistencies using Cronbach's alpha, with 15 instruments reporting Cronbach's alpha > 0.70 for the scale or its subscales.
Twenty-two instruments with a reported development or validation process to measure e-cigarette related constructs are currently available for practitioners and researchers. This review provides a guide for practitioners and researchers seeking to identify the most appropriate existing instruments on e-cigarette use based on the constructs examined, target population, psychometric properties, and instrument length. The gaps identified in the existing e-cigarette related instruments indicate that future studies should seek to extend the validity of the instruments for diverse populations, including adolescents. Instruments that explore additional aspects of e-cigarette use and e-cigarette related constructs to help build a strong theoretical background and expand our current understanding of e-cigarette use and its related constructs, should also be developed.
With the successful development in computer vision, building a deep convolutional neural network (CNNs) has been mainstream, considering the character of shared parameters in a convolutional layer. ...Stacking convolutional layers into a deep structure improves performance, but over-stacking also ramps up the needed resources for GPUs. Seeing another surge of Transformers in computer vision, the issue has aroused severely. A resource-hungry model is hardly implemented for limited hardware or single-customers-based GPU. Therefore, this work focuses on these concerns and proposes an efficient but robust backbone, which equips with channel and spatial direction attentions, so the attentions help to expand receptive fields in shallow convolutional layers and pass the information to every layer. An attention-boosted network based on already efficient CNNs, Universal Pixel Attention Networks (UPANets), is proposed. Through a series of experiments, UPANets fulfil the purposes of learning global information with less needed resources and outshine many existing SOTAs in CIFAR-{10, 100}.
Seven hydrazide-containing triphenylenedicarboxyimides (TDIs) bearing four β-octyloxy side chains and one alkyl acid amide group at the imide nitrogen have been synthesised. These TDIs exhibit ...enantiotropic mesophases with broad mesomorphic temperature ranges and high clearing temperatures between 258°C and 318°C. Notably, TDI-NHCO-C
4
H
9
with a n-butyl side chain exhibits a wide mesomorphic temperature range of over 300°C extending from below room temperature to 303°C. In contrast, its branched isomer TDI-NHCO-C(CH
3
)
3
carrying a bulky tert-butyl chain displays a hexagonal columnar mesophase between 105°C and 318°C with the highest clearing temperature within the series, indicating that branching leads to a stabilisation of the mesophase. On the other hand, the approximately 83°C increase in the clearing temperature of hydrazide TDI-NHCO-C
4
H
9
relative to imide TDI-C
4
H
9
lacking the hydrazide function indicates a significant enhancement of mesophase stability upon introducing the hydrazide functional group. However, variable-temperature infrared studies revealed the presence of weaker hydrogen bonds below the clearing temperature, which do not significantly contribute to the stabilisation of the columnar mesophase. Instead, the primary stabilisation mechanism is attributed to the synergistic effect of π-π interactions and dipole-dipole interactions.
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