De novo transcriptome assembly database for 100 tissues from each of seven species of domestic herbivore.

Domesticated herbivores are an important agricultural resource that play a critical role in global food security, particularly as they can adapt to varied environments, including marginal lands. An understanding of the molecular basis of their biology would contribute to better management and sustainable production. Thus, we conducted transcriptome sequencing of 100 to 105 tissues from two females of each of seven species of herbivore (cattle, sheep, goats, sika deer, horses, donkeys, and rabbits) including two breeds of sheep. The quality of raw and trimmed reads was assessed in terms of base quality, GC content, duplication sequence rate, overrepresented k-mers, and quality score distribution with FastQC. The high-quality filtered RNA-seq raw reads were deposited in a public database which provides approximately 54 billion high-quality paired-end sequencing reads in total, with an average mapping rate of ~93.92%. Transcriptome databases represent valuable resources that can be used to study patterns of gene expression, and pathways that are related to key biological processes, including important economic traits in herbivores.

Determination of 10 mycotoxins in wine, baijiu, and huangjiu of the Chinese market by liquid chromatography tandem mass spectrometry and exposure estimation.

In this study, liquid chromatography tandem mass spectrometry (LC-MS/MS) was employed to analyze the prevalence of 10 mycotoxins in 140 samples from the Chinese market, aiming to assess the exposure of Chinese individuals to these mycotoxins through the consumption of wine, baijiu, and huangjiu. Mycotoxins were detected in 98% of the samples, with fumonisins (FBs), deoxynivalenol (DON), and zearalenone (ZEN) exhibiting positive rates exceeding 50%. Regarding the exposure of the Chinese population to mycotoxins resulting from alcoholic beverage consumption, fruit wine intake made a relatively significant contribution to aflatoxin exposure, while baijiu showed a relatively significant contribution to ZEN exposure (1.84%). The analysis of the correlation between grape variety, wine region, and mycotoxin content demonstrated that FBs, ZEN, and DON were significantly influenced by grape variety and wine region. This research holds great significance in protecting human life and health, as well as in the production of safer alcoholic beverages.

Economic Evaluation of COVID-19 Immunization Strategies: A Systematic Review and Narrative Synthesis.

OBJECTIVES: This study aimed to systematically assess global economic evaluation studies on COVID-19 vaccination, offer valuable insights for future economic evaluations, and assist policymakers in making evidence-based decisions regarding the implementation of COVID-19 vaccination. METHODS: Searches were performed from January 2020 to September 2023 across seven English databases (PubMed, Web of Science, MEDLINE, EBSCO, KCL-Korean Journal Dataset, SciELO Citation Index, and Derwent Innovations Index) and three Chinese databases (Wanfang Data, China Science and Technology Journal, and CNKI). Rigorous inclusion and exclusion criteria were applied. Data were extracted from eligible studies using a standardized data collection form, with the reporting quality of these studies assessed using the Consolidated Health Economic Evaluation Reporting Standards 2022 (CHEERS 2022). RESULTS: Of the 40 studies included in the final review, the overall reporting quality was good, evidenced by a mean score of 22.6 (ranging from 10.5 to 28). Given the significant heterogeneity in fundamental aspects among the studies reviewed, a narrative synthesis was conducted. Most of these studies adopted a health system or societal perspective. They predominantly utilized a composite model, merging dynamic and static methods, within short to medium-term time horizons to simulate various vaccination strategies. The research strategies varied among studies, investigating different doses, dosages, brands, mechanisms, efficacies, vaccination coverage rates, deployment speeds, and priority target groups. Three pivotal parameters notably influenced the evaluation results: the vaccine's effectiveness, its cost, and the basic reproductive number (R0). Despite variations in model structures, baseline parameters, and assumptions utilized, all studies identified a general trend that COVID-19 vaccination is cost-effective compared to no vaccination or intervention. CONCLUSIONS: The current review confirmed that COVID-19 vaccination is a cost-effective alternative in preventing and controlling COVID-19. In addition, it highlights the profound impact of variables such as dose size, target population, vaccine efficacy, speed of vaccination, and diversity of vaccine brands and mechanisms on cost effectiveness, and also proposes practical and effective strategies for improving COVID-19 vaccination campaigns from the perspective of economic evaluation.

Development and validation of a liquid chromatography tandem mass spectrometry method for the determination of 10 mycotoxins in beer of the Chinese market and exposure estimate.

Mycotoxins are important risk factors in beer. In this study, a liquid chromatography tandem mass spectrometry (LC-MS/MS) method was developed to determine 10 mycotoxins in beer within 6 min. The method is fast, efficient, and has a simple and quick sample preparation. Validation was conducted based on the performance standards specified in Commission Decision 657/2002/EC, and the results demonstrated excellent linearity (R2 > 0.99), repeatability (RSD < 5 %), quantification limits (0.005-20.246 µg/L), and recovery rates (77 %-118 %). The prevalence of the 10 mycotoxins in 96 beers purchased from the Chinese market was analyzed, and the exposure of the Chinese population to mycotoxins through beer consumption was assessed. Deoxynivalenol (DON) was detected in 93.75 % of the beers, and the incidence of fumonisins (FBs) and zearalenone (ZEN) exceeded 50 %. Beer intake contributed significantly to the exposure of aflatoxins (AFs) and DON, especially in males. Correlation analysis between mycotoxin content in beer, raw materials, and the brewing process revealed that the brewing process significantly affected the content of DON (P < 0.001), while auxiliary materials also had a significant impact on the content of FBs and DON (P < 0.001). This study holds great significance in producing higher quality and safer beer.

Effects of Active Ingredients in Alcoholic Beverages and Their De-Alcoholized Counterparts on High-Fat Diet Bees: A Comparative Study.

The mechanisms by which alcohol, alcoholic beverages, and their de-alcoholized derivatives affect animal physiology, metabolism, and gut microbiota have not yet been clarified. The polyphenol, monosaccharide, amino acid, and organic acid contents of four common alcoholic beverages (Chinese Baijiu, beer, Chinese Huangjiu, and wine) and their de-alcoholized counterparts were analyzed. The research further explored how these alcoholic beverages and their non-alcoholic versions affect obesity and gut microbiota, using a high-fat diet bee model created with 2% palm oil (PO). The results showed that wine, possessing the highest polyphenol content, and its de-alcoholized form, particularly when diluted five-fold (WDX5), markedly improved the health markers of PO-fed bees, including weight, triglycerides, and total cholesterol levels in blood lymphocytes. WDX5 treatment notably increased the presence of beneficial microbes such as Bartonella, Gilliamella, and Bifidobacterium, while decreasing Bombilactobacillus abundance. Moreover, WDX5 was found to closely resemble sucrose water (SUC) in terms of gut microbial function, significantly boosting short-chain fatty acids, lipopolysaccharide metabolism, and associated enzymatic pathways, thereby favorably affecting metabolic regulation and gut microbiota stability in bees.

Upadacitinib sustained-release tablets for the treatment of chronic refractory gouty arthritis: a case report and literature review.

Background: Gouty arthritis (GA) is a crystal-related joint disease caused by the deposition of monosodium urate (MSU) crystals, directly associated with hyperuricemia resulting from purine metabolism disorder and/or reduced uric acid excretion. Acute attacks of typical gouty arthritis are generally relieved through the clinical use of NSAIDs, colchicine, or glucocorticoids. However, managing patients with chronic refractory gout poses challenges due to complications such as multiple tophi, gouty nephropathy, diabetes, and gastrointestinal bleeding. While there have been numerous studies on gout in recent years, research specifically regarding chronic refractory gout remains limited. The management of such cases still faces several unresolved issues, including recurrent disease flare-ups and poor patient compliance leading to inadequate drug utilization and increased risk of side effects. In this report, we present a case of successful improvement in chronic refractory gouty arthritis using the biologic agent upadacitinib sustained-release tablets. Case presentation: Our case report involves a 53 years-old Asian patient with recurrent gouty arthritis who had a history of over 20 years without regular treatment, presenting with tophi and an increasing number of painful episodes. During hospitalization, various analgesics and anti-inflammatory drugs provided inadequate relief, requiring the use of steroids to alleviate symptoms. However, tapering off steroids proved challenging. We decided to add upadacitinib sustained-release tablets to the treatment regimen, which ultimately improved the patient's condition. After 6 months of follow-up, the patient has not experienced any further acute pain episodes. Conclusion: This case highlights the potential therapeutic effect of upadacitinib sustained-release tablets during the acute phase of chronic refractory gouty arthritis.

Enhancing the flavour quality of Laiyang pear wine by screening sorbitol-utilizing yeasts and co-fermentation strategies.

This study took a novel approach to address the dual challenges of enhancing the ethanol content and aroma complexity in Laiyang pear wine. It focused on sorbitol as a pivotal element in the strategic selection of yeasts with specific sorbitol-utilization capabilities and their application in co-fermentation strategies. We selected two Saccharomyces cerevisiae strains (coded as Sc1, Sc2), two Metschnikowia pulcherrima (coded as Mp1, Mp2), and one Pichia terricola (coded as Tp) due to their efficacy as starter cultures. Notably, the Sc2 strain, alone or with Mp2, significantly increased the ethanol content (30% and 16%). Mixed Saccharomyces cerevisiae and Pichia terricola fermentation improved the ester profiles and beta-damascenone levels (maximum of 150%), while Metschnikowia pulcherrima addition enriched the phenethyl alcohol content (maximum of 330%), diversifying the aroma. This study investigated the efficacy of strategic yeast selection based on sorbitol utilization and co-fermentation methods in enhancing Laiyang pear wine quality and aroma.

Intestinal strictures in Crohn's disease: An update from 2023.

Crohn's disease (CD) is a chronic inflammatory disease that leads to intestinal stricture in nearly 35% of cases within 10 years of initial diagnosis. The unknown pathogenesis, lack of universally accepted criteria, and absence of an effective management approach remain unconquered challenges in structuring CD. The pathogenesis of stricturing CD involves intricate interactions between factors such as immune cell dysbiosis, fibroblast activation, and microecology imbalance. New techniques such as single-cell sequencing provide a fresh perspective. Non-invasive diagnostic tools such as serum biomarkers and novel cross-sectional imaging techniques offer a precise understanding of intestinal fibrostenosis. Here, we provide a timely and comprehensive review of the worthy advancements in intestinal strictures in 2023, aiming to dispense cutting-edge information regarding fibrosis and to build a cornerstone for researchers and clinicians to make greater progress in the field of intestinal strictures.

Successful management of fatal cardiac tamponade resulting from intravascular intervention for central vein occlusion in hemodialysis patients: A case report.

This case report highlights the successful management of fatal cardiac tamponade caused by intravascular intervention for central vein occlusion in hemodialysis patients. Prompt diagnosis and treatment are essential for patient prognosis in such cases. We present a case involving a challenging surgical procedure to address multiple complications, emphasizing the importance of early detection and appropriate interventions. The patient, who had a history of long-term central venous catheter use for hemodialysis, was diagnosed with central vein stenosis in addition to superior vena cava occlusion, hemodialysis catheter rupture, hypertension, and end-stage renal disease. Urgent ultrasound examination during surgery revealed pericardial effusion, prompting immediate pericardial drainage for stabilization. To overcome the complex challenges, we successfully performed an innominate vein-right atrial appendage bypass to restore vascular access and salvage the patient's life. The timely use of echocardiography for diagnosis and pericardial drainage contributed to stabilizing the patient's vital signs, providing an opportunity for subsequent surgical intervention. The innominate vein-right atrial appendage bypass procedure successfully relieved central vein stenosis and saved the patient's life. Although this surgical technique is not widely documented in hemodialysis patients with central venous involvement, it show cases the potential benefits for clinicians managing vascular access in this patient population. This case report underscores the need for awareness among clinicians regarding the risk of cardiac tamponade associated with intravascular intervention for central vein stenosis in hemodialysis patients. Minimizing central venous catheterization and prioritizing autogenous arteriovenous fistulas are crucial principles in preparing vascular access for hemodialysis patients. Early detection, timely interventions, and consideration of alternative surgical techniques can improve outcomes and prevent life-threatening complications.

Opinion Evolution with Information Quality of Public Person and Mass Acceptance Threshold.

Public persons are nodes with high attention to public events, and their opinions can directly affect the development on events. However, because of rationality, the followers' acceptance to the public persons' opinions will depend on the information trait on public persons' opinions and own comprehension. To study how different opinions of the public persons guide different followers, we build an opinion dynamics model, which would provide a theoretical method for public opinion management. Based on the classical bounded confidence model, we extract the information quality variables and individual trust threshold and introduce them to construct our two-stage opinion evolution model. And then in the simulation experiments, we analyze the different effects of opinion information quality, opinion release time, and frequency on public opinion by adjusting the different parameters. Finally, we added a case to compare real data, the data from classical model simulation and the data from improved model simulation to verify the effectiveness on our model. The research found that the more sufficient the argument and the more moderate the attitude, the more likely to guide the public opinion. If public person holds different opinions and different information quality, he should choose different time to present his opinion to achieve ideal guide effect. When public person holds neutral opinion and the information quality is relatively general, he/she can intervene in public opinion as soon as possible to control final public opinion; when public person holds extreme opinion and the information quality is relatively high, he/she can choose to express opinion after a certain period on public opinion evolution, which is conducive to improve the guidance effect on public opinion. The frequency of releasing opinions of public person consistently has a positive impact on the final public opinion.

The solution structure of human leptin reveals a conformational plasticity important for receptor recognition.

Leptin is a multi-potency cytokine that regulates various physiological functions, including weight control and energy homeostasis. Signaling of leptin is also important in many aging-related diseases. Leptin is required for the noncovalent crosslinking of different extracellular domains of leptin receptors, which is critical for receptor activation and downstream signaling. Nevertheless, the structure of intact apo-form leptin and the structural transition leptin undergoes upon receptor binding are not fully understood yet. Here, we determined the monomeric structure of wild-type human leptin by solution-state nuclear magnetic resonance spectroscopy. Leptin contains an intrinsically disordered region (IDR) in the internal A-B loop and the flexible helix E in the C-D loop, both of which undergo substantial local structural changes when leptin binds to its receptor. Our findings provide further insights into the molecular mechanisms of leptin signaling.

Cardiovascular safety of zoledronic acid in the treatment of primary osteoporosis: A meta-analysis and systematic review.

PURPOSE: Osteoporosis is intimately linked to cardiovascular disease and it has been uncertain that zoledronic acid is not correlated with cardiovascular disease. We intended to assess the cardiovascular safety of zoledronic acid in the treatment of primary osteoporosis. METHODS: We included only randomized controlled trials (RCTs) of patients with osteoporosis receiving zoledronic acid or a placebo. We systematically searched PubMed, Embase, Web of Science, Cochrane CENTRAL, Scopus, the Chinese National Knowledge Infrastructure, ClinicalTrials.gov, and ICTRP from the time of database creation to April 5, 2023. Two investigators extracted data independently on study characteristics, outcomes of interest, and risk of bias based on PRISMA guidelines. RESULTS: As of April 5, 2023, our search identified 32,361 records, and after excluding these records, 9 RCTs were included in the meta-analysis. The overall risk ratio for cardiovascular events with zoledronic acid for primary osteoporosis compared with placebo was 1.15 (95 % CI 1.05-1.26, I2=12 %, P = 0.002), while the risk of major adverse cardiovascular events with zoledronic acid (RR 1.03, 95 % CI 0. 89-1.18, I2=21 %, P = 0.71) was not significant, possibly due to atrial fibrillation (RR 1.21, 95 % CI 0.99-1.47, I2=0 %, P = 0.06) versus the increased relative risk of arrhythmia (RR 1.30, 95 % CI 1.11-1.52, I2=34 %, P = 0.001). Overall, the cardiovascular risk of zoledronic acid for the treatment of primary osteoporosis was not significant; however, the relative risk of elevated atrial fibrillation and arrhythmias remains to be further studied. CONCLUSIONS: In women with primary osteoporosis, zoledronic acid may increase the risk of atrial fibrillation (P = 0.06) and arrhythmias (P = 0.001) compared with placebo, independent of the risk of major adverse cardiovascular events, angina, and heart failure. However, the sample size of men with primary osteoporosis is small, and the cardiovascular risk of zoledronic acid in men with osteoporosis is uncertain.

A head-to-head comparison of the measurement properties of EQ-5D-3L and EQ-5D-5L in Chinese family caregivers of cancer patients.

BACKGROUND: Although both EQ-5D-3L(3L) and EQ-5D-5L(5L) have demonstrated good measurement properties in several patient populations, there is currently limited evidence comparing the measurement properties of 3L and 5L in family caregivers (FCs) of cancer patients. PURPOSE: This study aimed to compare the measurement properties of 3L and 5L in a sample of family caregivers of cancer patients. METHODS: A consecutive sample of FCs of cancer patients recruited from three tertiary hospitals were invited to complete the two versions of the EQ-5D in two rounds of interviews. We compared i) the ceiling effect using the McNemar's test, ii) test-retest reliability using intraclass correlation coefficient (ICC) and Cohen's Kappa, iii) convergent validity using Spearman's rank correlation coefficient, iv) known-group validity using F-statistic, v) and discriminant capacity using ordinal logistic regression. RESULTS: A total of 416 FCs completed the baseline questionnaire and 120 caregivers completed the follow-up questionnaire. Ceiling effects were smaller in 5L (12.5%) than in 3L (20.7%). The convergent validity (r = 0.344-0.771), known-groups validity (Fratio5L/3L = 2.06-4.09), discriminant capacity (ES = 0.341-0.396), and test-retest reliability (ICC = 0.725) of the 5L were slightly better than those of the 3L in China. CONCLUSION: The current study found both 3L and 5L to be suitable for use by FCs of cancer patients. However, 5L showed superior measurement properties compared to 3L and therefore could be the preferred instrument when EQ-5D data of cancer patients FCs is required.

Robust superhydrophobic silicone/epoxy functional coating with excellent chemical stability and self-cleaning ability.

Superhydrophobic surfaces have attracted broad attention because of their unique water repellency but are restricted by poor wear resistance, weak adhesion to the substrate, and complex fabrication processes. Herein, a double-layer coating strategy consisting of the amino fluorine-silicone resin/epoxy resin (AFSR/EP) system is created. The system features a high hardness and transparent hydrophobic interface adhesive layer through the amine-epoxy "click" chemical reaction. The environmentally friendly resin system and low-cost nano-silica particles (n-SiO2) are composited and sprayed onto the substrate surface to form a superhydrophobic layer with outstanding robustness and excellent environmental stability. The prepared AFSR/EP@n-SiO2 composite coatings have a water contact angle of 161.1° and a sliding angle of 3.4°, demonstrating high superhydrophobic properties. Benefitting from the complementary advantages of silicone/epoxy resin, the prepared composite coatings maintain remarkable water repellency after various harsh environmental tests, including cyclic mechanical abrasion and tape-stripping, acid-base (pH 1 and pH 14) treatment, 10 wt% NaCl (pH 7) salt solution immersion, temperature treatment, knife scratching, and long-term ultraviolet radiation treatment, showing reinforced mechanical robustness and durable anti-corrosion stability. Notably, surface hardness of 5H and optical transparency over 80% can be achieved. The simple method offers a novel approach for the large-scale preparation of multifunctional superhydrophobic coatings.

The interface-mediated electron structure tuning of RuOx-Co3O4 nano-particles for efficient electrocatalytic nitrate reduction.

The energy-intensive processes for the industrial production of ammonia necessitates the development of new methods to be proposed that will aid in reducing the global energy consumption. Specifically, the electrocatalytic nitrate reduction reaction (NO3RR) to produce ammonia is more thermodynamically feasible than the electrocatalytic nitrogen reduction reaction (NRR). However, it is hindered by a low catalytic activity due to its complex reaction pathways. Herein, we synthesized a novel electrocatalyst, RuOx-Co3O4 nanoparticles, with abundant interfaces, which exhibited an enhanced catalytic activity for efficient ammonia synthesis. This catalyst delivered a partial current density of 65.8 mA cm-2 for NH3 production, a faradaic efficiency (FE) of 89.7%, and a superior ammonia yield rate of up to 210.5 µmol h-1 cm-2 at -0.6 V vs. RHE. X-ray photoelectron and Raman spectroscopy revealed that the formed interfacial Ru-O-Co bond can decorate the electronic structures of the active sites and accelerate the absorption of NO3-, thus promoting the production of ammonia.

Comparative and phylogenetic analyses of mitochondrial genomes in Elateridae (Coleoptera: Elateroidea).

The click-beetles (Elateridae) are a species-rich beetle family that is easily recognizable. They are distributed in all zoogeographical regions with over 11,000 species. Comparative studies of the structural characteristics of mitochondrial genomes (mitogenomes), as well as phylogenetic relationships of click-beetles, can improve our understanding of mitogenomic evolution. In this study, we determined four mitogenomes from Elateridae by next-generation sequencing. The four mitogenomes were 16,005 to 16,930 bp in length with 37 typical genes and a control region (A + T-rich region). Combined with previously reported elaterid mitogenomes, all PCGs initiate with either the standard start codon of ATN or TTG. According to the nonsynonymous/synonymous mutation ratio (Ka/Ks) of all PCGs, the highest and the lowest evolutionary rates were found for atp8 and cox1, respectively. Among the control regions of the four mitogenomes, several different patterns and numbers of tandem repeats were identified, which was the primary cause of the length variation in control regions. Phylogenetic analyses were conducted based on 13 protein-coding genes and two ribosomal RNA genes from 33 species of Elateridae and two outgroups. The Bayesian inference and maximum likelihood trees had an identical topological structure. The monophyly of Cardiophorinae, Agrypninae and Elaterinae was recovered with high support in all topologies, and the Tetralobinae was placed as the earliest branch in the Elateridae. Expanding the availability of mitogenomic and genomic data from a broader range of click-beetles could provide more clarity on the disputed relationships among subfamilies within Elateridae.

Improvement of the fibrinolytic activity, acid resistance and thermostability of nattokinase by surface charge engineering.

Nattokinase is a promising thrombolytic drug due to its powerful fibrinolytic effect and few side effects. However, the low fibrinolytic activity and stability of nattokinase have limited its industrial production and oral application. In this study, the basic and neutral amino acid residues on the surface of recombinant nattokinase AprY from Bacillus mojavensis LY-06 (rAprY) were mutated to acidic amino acid residues by surface charge engineering strategy, and two variants K12D and N109D with 92.6 % and 8.4 % increased fibrinolytic activity were obtained. The R45E variant with enhanced acid stability and thermostability was also screened, its acid stability at pH 4 and t1/2 at 55 °C were 3.7-fold and 1.8-fold higher than that of wild type rAprY, respectively. Bioinformatics analysis showed that the increased activities of K12D and N109D variants were related to the increased flexibility of the region around their active centers. The increased rigidity of 97-103 amino acid residues around the active center of R45E may be the reason for its enhanced stability and reduced catalytic activity. The multipoint mutation K12D-N109D (M2)'s catalytic activity did not increase cumulatively, but its pH stability did. The nattokinase variants generated in this study have potential for industrial production and application.

Research on named entity recognition of adverse drug reactions based on NLP and deep learning.

Introduction: Adverse drug reactions (ADR) are directly related to public health and become the focus of public and media attention. At present, a large number of ADR events have been reported on the Internet, but the mining and utilization of such information resources is insufficient. Named entity recognition (NER) is the basic work of many natural language processing (NLP) tasks, which aims to identify entities with specific meanings from natural language texts. Methods: In order to identify entities from ADR event data resources more effectively, so as to provide valuable health knowledge for people, this paper introduces ALBERT in the input presentation layer on the basis of the classic BiLSTM-CRF model, and proposes a method of ADR named entity recognition based on the ALBERT-BiLSTM-CRF model. The textual information about ADR on the website "Chinese medical information query platform" (https://www.dayi.org.cn) was collected by the crawler and used as research data, and the BIO method was used to label three types of entities: drug name (DRN), drug component (COM), and adverse drug reactions (ADR) to build a corpus. Then, the words were mapped to the word vector by using the ALBERT module to obtain the character level semantic information, the context coding was performed by the BiLSTM module, and the label decoding was using the CRF module to predict the real label. Results: Based on the constructed corpus, experimental comparisons were made with two classical models, namely, BiLSTM-CRF and BERT-BiLSTM-CRF. The experimental results show that the F 1 of our method is 91.19% on the whole, which is 1.5% and 1.37% higher than the other two models respectively, and the performance of recognition of three types of entities is significantly improved, which proves the superiority of this method. Discussion: The method proposed can be used effectively in NER from ADR information on the Internet, which provides a basis for the extraction of drug-related entity relationships and the construction of knowledge graph, thus playing a role in practical health systems such as intelligent diagnosis, risk reasoning and automatic question answering.

Characteristics of health-state utilities used in cost-effectiveness analyses: a systematic review of published studies in Asia.

INTRODUCTION: Cost-utility analysis (CUA) is the preferred form of economic evaluation in many countries. As one of the key data inputs in cost-utility models, health state utility (HSU) has a crucial impact on CUA results. In the past decades, health technology assessment has been expanding rapidly in Asia, yet research examining the methodology and process used to generate cost-effectiveness evidence is scarce. The aim of this study was to examine the reporting of the characteristics of HSU data used in CUAs in Asia and how the characteristics have changed over time. METHODS: A systematic literature search was performed to identify published CUA studies targeting Asian populations. Information was extracted for both the general characteristics of selected studies and the characteristics of reported HSU data. For each HSU value identified, we extracted data for four key characteristics, including 1) estimation method; 2) source of health-related quality of life (HRQoL) data; 3) source of preference data; and 4) sample size. The percentage of nonreporting was calculated and compared over two time periods (1990-2010 vs 2011-2020). RESULTS: A total of 789 studies were included and 4,052 HSUs were identified. Of these HSUs, 3,351 (82.7%) were from published literature and 656 (16.2%) were from unpublished empirical data. Overall, the characteristics of HSU data were not reported in more than 80% of the studies. Of HSUs whose characteristics were reported, most of them were estimated using the EQ-5D (55.7%), Asian HRQoL data (91.9%), and Asian health preferences (87.7%); 45.7% of the HSUs was estimated with a sample of 100 or more individuals. All four characteristics showed improvements after 2010. CONCLUSION: Over the past two decades, there has been a significant increase in CUA studies targeting Asian populations. However, HSU's characteristics were not reported in most of the CUA studies, making it difficult to evaluate the quality and appropriateness of the HSUs used in those cost-effectiveness studies.

Structural insights of the toxin-antitoxin system VPA0770-VPA0769 in Vibrio parahaemolyticus.

Toxin-antitoxin (TA) systems are involved in both normal bacterial physiology and pathogenicity, including gene regulation, antibiotic resistance, and bacteria persistence under stressful environments. In pathogenic Vibrio parahaemolyticus, however, TA interaction and assembly remain largely unknown. In this work, we identified a new RES-Xre type II TA module, encoded by gene cluster vpa0770-vpa0769 on chromosome II of V. parahaemolyticus. Ectopic expression of the VPA0770 toxin rapidly arrests the growth of E. coli cells, which can be neutralized by co-expression of the VPA0769 antitoxin. To decipher the action mechanism, we determined the crystal structure of the VPA0770-VPA0769 TA complex. VPA0770 and VPA0769 proteins can assemble into two types of large complexes, a W-shaped hetero-hexamer and a donut-like hetero-dodecamer, in a concentration-dependent manner in solution. Disruption of the TA interface results in a loss of the antitoxic phenotype. The toxicity of the VPA0770 toxin, which harbors a NAD+-binding pocket, may be largely ascribed to its highly effective capability to degrade intracellular NAD+. Our study provides a structural basis for a better understanding of diverse molecular mechanisms employed by human pathogens.