Clinical evaluation of droplet digital PCR in the early identification of suspected sepsis patients in the emergency department: a prospective observational study.

Background: Rapid and accurate diagnosis of the causative agents is essential for clinical management of bloodstream infections (BSIs) that might induce sepsis/septic shock. A considerable number of suspected sepsis patients initially enter the health-care system through an emergency department (ED), hence it is vital to establish an early strategy to recognize sepsis and initiate prompt care in ED. This study aimed to evaluate the diagnostic performance and clinical value of droplet digital PCR (ddPCR) assay in suspected sepsis patients in the ED. Methods: This was a prospective single-centered observational study including patients admitted to the ED from 25 October 2022 to 3 June 2023 with suspected BSIs screened by Modified Shapiro Score (MSS) score. The comparison between ddPCR and blood culture (BC) was performed to evaluate the diagnostic performance of ddPCR for BSIs. Meanwhile, correlative analysis between ddPCR and the inflammatory and prognostic-related biomarkers were conducted to explore the relevance. Further, the health economic evaluation of the ddPCR was analyzed. Results: 258 samples from 228 patients, with BC and ddPCR performed simultaneously, were included in this study. We found that ddPCR results were positive in 48.13% (103 of 214) of episodes, with identification of 132 pathogens. In contrast, BC only detected 18 positives, 88.89% of which were identified by ddPCR. When considering culture-proven BSIs, ddPCR shows an overall sensitivity of 88.89% and specificity of 55.61%, the optimal diagnostic power for quantifying BSI through ddPCR is achieved with a copy cutoff of 155.5. We further found that ddPCR exhibited a high accuracy especially in liver abscess patients. Among all the identified virus by ddPCR, EBV has a substantially higher positive rate with a link to immunosuppression. Moreover, the copies of pathogens in ddPCR were positively correlated with various markers of inflammation, coagulation, immunity as well as prognosis. With high sensitivity and specificity, ddPCR facilitates precision antimicrobial stewardship and reduces health care costs. Conclusions: The multiplexed ddPCR delivers precise and quantitative load data on the causal pathogen, offers the ability to monitor the patient's condition and may serve as early warning of sepsis in time-urgent clinical situations as ED. Importance: Early detection and effective administration of antibiotics are essential to improve clinical outcomes for those with life-threatening infection in the emergency department. ddPCR, an emerging tool for rapid and sensitive pathogen identification used as a precise bedside test, has developed to address the current challenges of BSI diagnosis and precise treatment. It characterizes sensitivity, specificity, reproducibility, and absolute quantifications without a standard curve. ddPCR can detect causative pathogens and related resistance genes in patients with suspected BSIs within a span of three hours. In addition, it can identify polymicrobial BSIs and dynamically monitor changes in pathogenic microorganisms in the blood and can be used to evaluate antibiotic efficacy and survival prognosis. Moreover, the copies of pathogens in ddPCR were positively correlated with various markers of inflammation, coagulation, immunity. With high sensitivity and specificity, ddPCR facilitates precision antimicrobial stewardship and reduces health care costs.

Relationship Between Product Features and the Prices of e-Cigarette Devices Sold in Web-Based Vape Shops: Comparison Study Using a Linear Regression Model.

BACKGROUND: Open-system electronic cigarette (EC) product features, such as battery capacity, maximum output wattage, and so forth, are major components that drive product costs and may influence use patterns. Moreover, continued innovation and monitoring of product features and prices will provide critical information for designing appropriate taxation policies and product regulations. OBJECTIVE: This study will examine how product features are associated with the prices of devices sold in web-based vape shops. METHODS: We draw samples from 5 popular, US-based, web-based vape shops from April to August 2022 to examine starter kits, device-only products, and e-liquid container-only products. We implemented a linear regression model with a store-fixed effect to examine the association between device attributes and prices. RESULTS: EC starter kits or devices vary significantly by type, with mod prices being much higher than pod and vape pen prices. The prices of mod starter kits were even lower than those of mod devices, suggesting that mod starter kits are discounted in web-based vape shops. The price of mod kits, mod device-only products, and pod kits increased as the battery capacity and output wattage increased. For vape pens, the price was positively associated with the volume size of the e-liquid container. On the other hand, the price of pod kits was positively associated with the number of containers. CONCLUSIONS: A unit-based specific tax, therefore, will impose a higher tax burden on lower-priced devices such as vape pens or pod systems and a lower tax burden on mod devices. A volume- or capacity-based specific tax on devices will impose a higher tax burden on vape pens with a larger container size. Meanwhile, ad valorem taxes pegged to wholesale or retail prices would apply evenly across device types, meaning those with advanced features such as higher battery capacities and output wattage would face higher rates. Therefore, policy makers could manipulate tax rates by device type to discourage the use of certain device products.

Cost Comparison and Spending on Tobacco Products: Evidence from A Nationally Representative Sample of Adult E-Cigarette Users.

Background: Over 20 states and local jurisdictions in the U.S. have imposed e-cigarette taxes. It is important to evaluate how adult vapers, including those who also smoke respond to e-cigarette taxation. The purpose of this study is to examine factors associated with adult vapers' cost perception of e-cigarettes relative to cigarettes and budget allocations between two products. Methods: We recruited a nationally representative sample of 801 adult e-cigarette users in the U.S., who participated in an online survey in April and May 2023. Nested-ordered logit models and ordinary least squares regressions were used in the analysis. Results: On average, monthly e-cigarette spending was $82.22, and cigarette spending was $118.77 among dual users. Less frequent e-cigarette use and higher state-level e-cigarette taxes were associated with perceiving smoking as cheaper than vaping. Age and exclusive use of tank systems were associated with perceiving vaping as cheaper than smoking. Exclusive use of tank systems was also associated with lower e-cigarette spending. Adults who used e-cigarettes more frequently preferred to report weekly budget on e-cigarettes ( p < 0.01), and among dual users, everyday smokers preferred to report weekly (versus monthly) budget on cigarettes compared to someday smokers ( p < 0.001). Conclusion: Among US adult vapers, frequencies of tobacco use and e-cigarette device type are closely related to cost measures; and e-cigarette taxes are associated with cost perception of e-cigarettes relative to cigarettes, suggesting potential financial disincentive for vaping. Policymaker may consider imposing differential taxes by e-cigarette product types due to their different costs to consumers.

Factors associated with the disease family burden of caregivers of myasthenia gravis patients in northwestern China: A cross-sectional study.

BACKGROUND: Patients with myasthenia gravis (MG) lose part of their working or living ability due to illness, and bring burden to caregivers. The purpose of this study was to explore the factors related to caregivers' disease family burden for MG patients in Northwest China. METHODS: The study utilized our Myasthenia Gravis database and distributed online questionnaires to both MG patients and their caregivers. The questionnaires included a general data collection form, the Patient Health Questionnaire-9 (PHQ-9) scale, and the Caregivers' Family Burden Scale of Disease (FBSD). Univariate analysis and multivariate linear regression analysis were run, with FBSD as the outcome variable for separate analyses. RESULTS: 178 MG patients were eligible for inclusion in the analysis, of whom 80 patients' caregivers had a positive family burden of MG. The daily activity burden of the family and the economic burden of the family were the heaviest among the six dimensions of the caregivers' family disease burdens. The factors independently associated with FBSD were depression symptom level, MG severity classification and family's monthly per capita income (p < 0.05). CONCLUSIONS: Depression symptom level, MG severity classification and family's monthly per capita income are independent factors related to the caregivers' disease family burden for MG patients.

Age affects the association between socioeconomic status and infertility: a cross-sectional study.

BACKGROUND: Previous studies have shown the interaction between age and socioeconomic status (SES) on the risk of infertility in the UK, but the association is still unclear in the United States. Therefore, the present study investigated the effect of age on the relationship between SES and the risk of infertility in American women. METHODS: The study included adults who participated in the National Health and Nutrition Examination Survey (NHANES) from 2013 to 2018. The poverty income ratio (PIR) was used to represent the SES of the population. With participants stratified according to age category (< 35 years; ≥ 35 years), we further assessed differences in the relationship between PIR and infertility risk among participants of different age groups using multivariate logistic regression and interaction tests. RESULTS: Approximately 3,273 participants were enrolled in the study. There were 399 cases of infertility and 2,874 cases without infertility. In women ≥ 35 years of age, PIR levels were significantly higher in infertile participants than in non-infertile participants, but no such difference was found in those < 35 years of age. The association of PIR with the risk of infertility appeared to differ between age < 35 years and age ≥ 35 years (OR: 0.99, 95%Cl: 0.86-1.13 vs. OR: 1.24, 95%Cl: 1.12-1.39) in a fully adjusted model. Furthermore, an interaction between age and PIR increased the risk of infertility (p-value for interaction < 0.001). CONCLUSION: Our study found that age may influence the association between PIR and infertility. It is imperative to perform further studies to provide more evidence.

Genotoxicity Assessment of Haloacetaldehyde Disinfection Byproducts via a Simplified Yeast-Based Toxicogenomics Assay.

Haloacetaldehydes (HALs) represent the third-largest category of disinfection byproducts (DBPs) in drinking water in terms of weight. As a subset of unregulated DBPs, only a few HALs have undergone assessment, yielding limited information regarding their genotoxicity mechanisms. Herein, we developed a simplified yeast-based toxicogenomics assay to evaluate the genotoxicity of five specific HALs. This assay recorded the protein expression profiles of eight Saccharomyces cerevisiae strains fused with green fluorescent protein, including all known DNA damage and repair pathways. High-resolution real-time pathway activation data and protein expression profiles in conjunction with clustering analysis revealed that the five HALs induced various DNA damage and repair pathways. Among these, chloroacetaldehyde and trichloroacetaldehyde were found to be positively associated with genotoxicity, while dichloroacetaldehyde, bromoacetaldehyde, and tribromoacetaldehyde displayed negative associations. The protein effect level index, which are molecular end points derived from a toxicogenomics assay, exhibited a statistically significant positive correlation with the results of traditional genotoxicity assays, such as the comet assay (rp = 0.830 and p < 0.001) and SOS/umu assay (rp = 0.786 and p = 0.004). This yeast-based toxicogenomics assay, which employs a minimal set of gene biomarkers, can be used for mechanistic genotoxicity screening and assessment of HALs and other chemical compounds. These results contribute to bridging the knowledge gap regarding the molecular mechanisms underlying the genotoxicity of HALs and enable the categorization of HALs based on their distinct DNA damage and repair mechanisms.

A novel culture-enriched metagenomic sequencing strategy effectively guarantee the microbial safety of drinking water by uncovering the low abundance pathogens.

Assessing the presence of waterborne pathogens and antibiotic resistance genes (ARGs) is crucial for managing the environmental quality of drinking water sources. However, detecting low abundance pathogens in such settings is challenging. In this study, a workflow was developed to enrich for broad spectrum pathogens from drinking water samples. A mock community was used to evaluate the effectiveness of various enrichment broths in detecting low-abundance pathogens. Monthly metagenomic surveillance was conducted in a drinking water source from May to September 2021, and water samples were subjected to five enrichment procedures for 6 h to recover the majority of waterborne bacterial pathogens. Oxford Nanopore Technology (ONT) was used for metagenomic sequencing of enriched samples to obtain high-quality pathogen genomes. The results showed that selective enrichment significantly increased the proportions of targeted bacterial pathogens. Compared to direct metagenomic sequencing of untreated water samples, targeted enrichment followed by ONT sequencing significantly improved the detection of waterborne pathogens and the quality of metagenome-assembled genomes (MAGs). Eighty-six high-quality MAGs, including 70 pathogen MAGs, were obtained from ONT sequencing, while only 12 MAGs representing 10 species were obtained from direct metagenomic sequencing of untreated water samples. In addition, ONT sequencing improved the recovery of mobile genetic elements and the accuracy of phylogenetic analysis. This study highlights the urgent need for efficient methodologies to detect and manage microbial risks in drinking water sources. The developed workflow provides a cost-effective approach for environmental management of drinking water sources with microbial risks. The study also uncovered pathogens that were not detected by traditional methods, thereby advancing microbial risk management of drinking water sources.

How cigarette excise tax pass-through to prices responds to the uptake and evolution of e-cigarettes (ECs).

BACKGROUND: How excise taxes are passed through to prices determines whether tax policies will be effective in changing smoking behaviours. Though previous literature has documented that cigarette taxes are overly shifted to prices, there is limited evidence on how cigarette tax pass-through to prices is affected by the uptake and evolution of e-cigarettes (ECs) in the US market. OBJECTIVE: This study investigates how cigarette excise tax pass-through rate varied by price levels (the 25th, 50th, and 75th percentile prices) and the uptake and evolution of ECs. METHODS: Tax pass-through rates were assessed using ordinary least squares regressions while controlling for state, year and month fixed effects. Different trends were then tested for the pre-EC uptake era (2006-2011), EC uptake era (2012-2016) and the evolution of nicotine salt-based ECs era (2017 and later). FINDINGS: Cigarette excise taxes were fully shifted to the 25th and 50th percentile prices and overly shifted to the 75th percentile prices at a 1:1.1 rate. While cigarette excise taxes had a continuous impact on raising prices, the tax pass-through rates were lower for lower priced cigarettes, and states imposed lower taxes. CONCLUSIONS: Continuing to raise cigarette taxes may be needed to create financial incentives to encourage people who smoke to switch to ECs. In addition, continuing to raise cigarette taxes and additional pricing policies such as price promotion restrictions are needed to increase retail prices and reduce price minimisation opportunities.

What types of e-liquid products were more likely to offer price promotions?

INTRODUCTION: The present study empirically examined the association between price discounts and product attributes of e-liquids sold by online retailers. METHODS: We analysed 14 000 e-liquid products from five major online e-cigarette retailers between April and May 2021 to determine the association between price discounts and product attributes such as nicotine level and form, flavour and vegetable glycerine/propylene glycol ratio. A fixed-effects model was used in the analysis and discounts were calculated in US cents/mL of e-liquid volume. RESULTS: Out of 14 407 e-liquid products, 92.5% were offered at a discounted price. On average, the price discount for the 13 324 products that had discounts was 16.84 cents/mL across the five stores. Among the three forms of nicotine (salt, freebase and nicotine free), salt e-liquids had the highest average price discount. CONCLUSION: Our findings suggest that e-liquids with salt nicotine have a higher average price discount when sold online, which may influence consumer purchasing behaviour. Further research is needed to assess the potential impact of these discounts on youth and adult tobacco use. Policymakers may consider implementing measures to limit online price discounts for e-liquids as a means of reducing sales among young people.

Metagenomic sequencing combined with flow cytometry facilitated a novel microbial risk assessment framework for bacterial pathogens in municipal wastewater without cultivation.

A workflow that combined metagenomic sequencing with flow cytometry was developed. The absolute abundance of pathogens was accurately estimated in mock communities and real samples. Metagenome-assembled genomes binned from metagenomic data set is robust in phylogenetic analysis and virulence profiling.

Distributions and Trends of the Global Burden of Colorectal Cancer Attributable to Dietary Risk Factors over the Past 30 Years.

Dietary risk has always been a major risk factor for colorectal cancer (CRC). However, the contribution of dietary risk factors to CRC at the level of region, gender, and age has not been fully characterized. Based on the Global Burden of Disease (GBD) 2019 study, the death rates, age-standardized mortality rates (ASDRs), and estimated annual percentage changes (EAPCs) were calculated to assess the trends of CRC attributable to dietary risk factors over the past 30 years. Globally, the death cases of CRC increased to 1,085,797 in 2019, and the number of deaths attributed to dietary risk factors increased to 365,752 in 2019, representing approximately one-third of all CRC-related fatalities. Overall, the ASDR attributable to dietary risks was 4.61 per 100,000 in 2019, with a slight downward trend (EAPC = -0.29). Notably, there is a rising trend in early-onset colorectal cancer mortality associated with dietary factors. To alleviate CRC burdens, it is recommended to elevate the intake of whole grains, milk, calcium, and fiber while reducing consumption of red and processed meats. The results will improve the understanding, and provide guidance on the diet of CRC in different regions, gender, and age groups worldwide.

Black soldier fly larvae effectively degrade lincomycin from pharmaceutical industry wastes.

Lincomycin fermentation residues (LFR) are the byproducts from the pharmaceutical industry, and contain high concentrations of antibiotics that could pose a threat to the environment. Here, we report that black soldier fly larvae (BSFL) and associated microbiota can effectively degrade LFR and accelerate the degradation of lincomycin in LFR. The degradation rate of lincomycin in LFR can reach 84.9% after 12 days of BSFL-mediated bioconversion, which is 3-fold greater than that accomplished with natural composting. The rapid degradation was partially carried out by the BSFL-associated microbiota, contributing 22.0% of the degradation in the final composts. Based on microbiome analysis, we found that the structure of microbiota from both BSFL guts and BSFL composts changed significantly during the bioconversion, and that several bacterial genera were correlated with lincomycin degradation. The roles of the associated microbiota in the degradation were further verified by the ability of two larval intestinal bacterial isolates and one bacterial isolate from BSFL composts to lincomycin degradation. The synergy between BSFL and the isolated strains resulted in a 2-fold increase in degradation compared to that achieved by microbial degradation alone. Furthermore, we determined that the degradation was correlated with the induction of several antibiotic resistant genes (ARGs) associated with lincomycin degradation in larval guts and BSFL composts. Moreover, the environmental conditions in the BSFL composts were found to be conducive to the degradation. In conclusion, these findings demonstrate that the BSFL-mediated bioconversion of LFR could effectively reduce residual lincomycin and that the associated microbiota play crucial roles in the process.

Metagenomics combined with comprehensive validation as a public health risk assessment tool for urban and agricultural run-off.

Early detection of emerging and life-threatening pathogens circulating in complex environments is urgently required to combat infectious diseases. This study proposed a public health risk assessment workflow with three stages, pathogen screening, pathogen genotyping, and risk assessment. In stage one, pathogens were screened with metagenomic sequencing, microfluidic chip, and qPCR. In stage two, pathogens were isolated and genotyped with multi-locus sequence typing (MLST) or conventional PCR. Finally, virulence genes from metagenomic data were assessed for pathogenicity. Two regions (Donggang and Zhanjiang) with potential public health concerns were selected for evaluation, each of which comprised of one urban and one farming wastewater sampling location. Overall, metagenomic sequencing reflected the variation in the relative abundance of medically important bacteria. Over 90 bacterial pathogens were monitored in the metagenomic dataset, of which 56 species harbored virulence genes. In Donggang, a pathogenic Acinetobacter sp. reached high abundances in 2018 and 2020, whereas all pathogenic Vibrio spp. peaked in October 2019. In Zhanjiang, A. baumanni, and other Enterobacteriaceae species were abundantly present in 2019 and 2020, whereas Aeromonas and Vibrio spp. peaked in November-2017. Forty species were subsequently isolated and subtyped by MLST, half of which were prevalent genotypes in clinical data. Additionally, we identified the African Swine Fever Virus (ASFV) in water samples collected in 2017, ahead of the first reported ASFV outbreak in 2018 in China. RNA viruses like Hepatitis A virus (HAV) and Enterovirus 71 (EV71) were also detected, with concentrations peaking in April 2020 and April 2018, respectively. The dynamics of HAV and EV71 were consistent with local epidemic trends. Finally, based on the virulence gene profiles, our study identified the risk level in wastewater of two cities. This workflow illustrates the potential for an early warning of local epidemics, which helps to prioritize the preparedness for specific pathogens locally.

Inhibition of EZH2 prevents acute respiratory distress syndrome (ARDS)-associated pulmonary fibrosis by regulating the macrophage polarization phenotype.

BACKGROUND: We recently reported histone methyltransferase enhancer of zeste homolog 2 (EZH2) as a key epigenetic regulator that contributes to the dysfunction of innate immune responses to sepsis and subsequent lung injury by mediating the imbalance of macrophage polarization. However, the role of EZH2 in acute respiratory distress syndrome (ARDS)-associated fibrosis remains poorly understood. METHODS: In this study, we investigated the role and mechanisms of EZH2 in pulmonary fibrosis in a murine model of LPS-induced ARDS and in ex-vivo cultured alveolar macrophages (MH-S) and mouse lung epithelial cell line (MLE-12) by using 3-deazaneplanocin A (3-DZNeP) and EZH2 the small interfering (si) RNA. RESULTS: We found that treatment with 3-DZNeP significantly ameliorated the LPS-induced direct lung injury and fibroproliferation by blocking EMT through TGF-ß1/Smad signaling pathway and regulating shift of macrophage phenotypes. In the ex-vivo polarized alveolar macrophages cells, treatment with EZH2 siRNA or 3-DZNeP suppressed the M1 while promoted the M2 macrophage differentiation through modulating the STAT/SOCS signaling pathway and activating PPAR-γ. Moreover, we identified that blockade of EZH2 with 3-DZNeP suppressed the epithelial to mesenchymal transition (EMT) in co-cultured bronchoalveolar lavage fluid (BALF) and mouse lung epithelial cell line through down-regulation of TGF-ß1, TGF-ßR1, Smad2 while up-regulation of Smad7 expression. CONCLUSIONS: These results indicate that EZH2 is involved in the pathological process of ARDS-associated pulmonary fibrosis. Targeting EZH2 may be a potential therapeutic strategy to prevent and treat pulmonary fibrosis post ARDS.

Demographic and social correlates and indicators for behavioural compliance with personal protection among Chinese community-dwellers during COVID-19: a cross-sectional study.

OBJECTIVES: Examine compliance with personal protective measures in communities for the prevention and control of local transmission of the COVID-19, and explore indicators for such behavioural compliance. DESIGN: Cross-sectional design with a self-selecting sample. Data collected in February 2020. SETTING: Community dwellers in China. PARTICIPANTS: 2956 participants aged 16 and above completed the study and were included in the analysis. OUTCOME MEASURES: Nationwide COVID-19 survey. Demographics and self-reported compliance with four personal protective measures-home quarantine, mask-wearing, temperature-taking and hand-sanitising were collected. Outbreak severity and timeliness of personal protection order were obtained from the China Center for Disease Control and Prevention website. Logistic regression models were employed to examine the association between demographic and social indicators and behavioural compliance. RESULTS: Compliance with home quarantine was only associated with gender (men, OR=0.61 (0.51-0.73), inverse association) but no other indicators. In contrast, men had higher compliance with mask-wearing (OR=1.79 (1.49-2.16)) and temperature-taking (OR=1.27 (1.05-1.53)). Compared with younger adults (≤20 years), the middle-age groups (31-40 and 41-50 years of age) were more compliant with all protective behaviours, except for home quarantine (OR=0.71 (0.54-0.93) and 0.67 (0.46-0.97), respectively). CONCLUSION: Male gender was associated with lower compliance with home quarantine yet higher compliance with mask-wearing and temperature-taking. The middle-age participants (31-50 years) had lower compliance with home quarantine but higher with other measures. These findings may be supported by the economic considerations and the long-inherited Confucian values among Chinese. In light of the ongoing COVID-19 pandemic, public health authorities should tailor policy implementation to disparities in psychosocial indicators.

Analysis on the relationship between fisheries economic growth and marine environmental pollution in China's coastal regions.

The rapid development of China's fisheries economy is accompanied by intensified marine environmental pollution over the period covered by this study. Based on data from multiple sources, this paper attempts to measure the relationship between fisheries economic growth and marine environmental pollution among China's coastal regions over the past 17 years. For this purpose, it firstly quantifies changes in fisheries economy and fisheries population. It then goes onto comparing the degree of changes in fisheries economy and marine environment. Finally, it depicts the relationship between fisheries added value (FAV) and polluted marine area (PMA) and between per capita net income of fishermen (PCNIF) and PMA ratio. Results suggest that.

Chinese Minority Perceives the Doctor-Patient Relationship Differently: A Cultural and Economic Interpretation.

In China, doctor-patient relationships (D-P relationships) are cited frequently and attracted international attention. This study assesses whether the D-P relationship experienced by the Chinese is associated with ethnicity, hospital hierarchies, and socioeconomic factors. In a national cross-sectional survey, multi-stage random sampling was adopted to assess regional and socio-economic differences between year 2016 and year 2017. Each area surveyed consisted of about 250 randomly chosen households, and valid results were obtained from 4,173 adults aged 16-99. When provided a choice of eight types of D-P relationship, for doctors in primary care institutions, 63.8% of ethnic minorities indicated having a friend-type relationship with their physicians, with 23.3% having a trading/reciprocal relationship. Han Chinese, however, predicts the opposite relationship between doctors from different hierarchy and the types of D-P relationship. For physicians working in hospitals, this difference in relationship was more pronounced, where 52.9% of ethnic minorities indicated having a friend-type relationship with their physicians, and 30.1% indicated the presence of a trading/reciprocal relationship. For Han Chinese, however, 53.3% indicated having a reciprocal relationship with their doctor. Overall, the prevalence of friendly D-P relationships was correlated with ethnic minorities, lower levels of education, and lower incomes. Ethnic minorities are most likely to perceive their physicians as friends, while Han Chinese are more likely to perceive a trading relationship with their physicians. The primary contribution of this research is the finding that D-P relationships differ for Han Chinese and other ethnic minorities.

A comprehensive assessment of Next-Generation Sequencing variants validation using a secondary technology.

BACKGROUND: Recently, increasing innovations improved the accuracy of next generation sequencing (NGS) data. However, the validation of all NGS variants increased the cost and turn-around time of clinical diagnosis, and therefore limited the further development of clinical applications. We aimed to comprehensively assess the necessity of validating NGS variants. METHODS: Validation data of 7,601 NGS variants involving 1,045 genes were collected from 5,190 clinical samples and sequenced by one of five targeted capture panels and two NGS chemistries, respectively. These genes and variants were widely distributed in 24 human chromosomes and mitochondrial genome. Variants validation was firstly processed by Sanger sequencing. If validation results were unavailable or inconsistent with NGS calls, another validation test would be performed by mass spectrometry genotyping. RESULTS: A total of 6,939 high quality NGS variants with ≥35 × depth coverage and ≥35% heterozygous ratio were 100% confirmed by a secondary methodology. 5,775 heterozygous variants were separated from 760 homozygous variants and 404 hemizygous variants by 80% heterozygous ratio. A total of 1.5% (98/6,939) of NGS variants were validated by mass spectrometry genotyping. CONCLUSION: Considering of the above comprehensive assessment, a new variant with high quality from a well-validated capture-based NGS workflow can be reported directly without validation.

Transferable Kinetic Monte Carlo Models with Thousands of Reactions Learned from Molecular Dynamics Simulations.

Molecular dynamics (MD) simulation of complex chemistry typically involves thousands of atoms propagating over millions of time steps, generating a wealth of data. Traditionally these data are used to calculate some aggregate properties of the system and then discarded, but we propose that these data can be reused to study related chemical systems. Using approximate chemical kinetic models and methods from statistical learning, we study hydrocarbon chemistries under extreme thermodynamic conditions. We discover that a single MD simulation can contain sufficient information about reactions and rates to predict the dynamics of related yet different chemical systems using kinetic Monte Carlo (KMC) simulation. Our learned KMC models identify thousands of reactions and run 4 orders of magnitude faster than MD. The transferability of these models suggests that we can viably reuse data from existing MD simulations to accelerate future simulation studies and reduce the number of new MD simulations required.

Quantitative Assessment of Molecular Transport through Sub-3 nm Silica Nanochannels by Scanning Electrochemical Microscopy.

Scanning electrochemical microscopy (SECM) has been proved to be a powerful technique to study molecular transport across ionic channels in biomembranes and artificial nanoporous membranes. In this work SECM was used to study the dynamics of molecular transport across the ultrathin silica nanoporous membrane consisting of sub-3 nm diameter perpendicular channels. We focused on the quantitative assessment of permselectivity and permeability of the membrane and the effect of radial electrical double layer (EDL) on them. By SECM imaging, it was phenomenologically observed that the membrane with negatively charged surface exhibited permselectivity to anionic molecule, for instance hexacyanoruthenate(II) (Ru(CN)64-). And the permselective transport of Ru(CN)64- was obviously more favored at a higher concentration of KCl. Precise membrane permeability to Ru(CN)64- was quantitatively determined by overlapping experimental SECM approach curves with the ones generated by finite element simulations. The high permeability up to 35 µm s-1 was ascribed to the straight channel structure and ultrahigh channel density of 4 × 1012 cm-2. Moreover, the permeability was varied from 35 µm s-1 to 2.5 µm s-1 when decreasing the concentration of KCl from 1.0 to 0.01 M, corroborating the electrostatic origin of membrane permselectivity. On the other hand, the simulated concentration profiles at both sides of the membrane suggested that the molecular transport across the membrane was mainly driven by the large transmembrane concentration gradient while the tip-induced transport was relatively negligible. These results help to quantitatively understand the molecular transport selectivity and dynamics across nanoporous membranes and to rationally design artificial molecular sieving membranes.