Assessment of sepsis-associated encephalopathy by quantitative magnetic resonance spectroscopy in a rat model of cecal ligation and puncture.

Proton magnetic resonance spectroscopy (1H-MRS) is the only non-invasive technique to quantify neurometabolic compounds in the living brain. We used 1H-MRS to evaluate the brain metabolites in a rat model of Sepsis-associated encephalopathy (SAE) established by cecal ligation and puncture (CLP). 36 male Sprague-Dawley rats were randomly divided into sham and CLP groups. Each group was further divided into three subgroups: subgroup O, subgroup M, and subgroup N. Neurological function assessments were performed on the animals in the subgroup O and subgroup N at 24 h, 48 h, and 72 h. The animals in the subgroup M were examined by magnetic resonance imaging (MRI) at 12 h after CLP. Compared with the sham group, the ratio of N-acetylaspartate (NAA) to creatine (Cr) in the hippocampus was significantly lower in the CLP group. The respective ratios of lactate (Lac), myo-inositol (mIns), glutamate and glutamine (Glx), lipid (Lip), and choline (Cho) to Cr in the CLP group were clearly higher than those in the sham group. Cytochrome c, intimately related to oxidative stress, was elevated in the CLP group. Neurofilament light (NfL) chain and glial fibrillary acidic protein (GFAP) scores in the CLP group were significantly higher than those in the sham group, while zonula occludens-1 (ZO-1) was downregulated. Compared with the sham group, the CLP group displayed higher values of oxygen extraction fraction (OEF), central venous-arterial partial pressure of carbon dioxide (P (cv-a) CO2), and central venous lactate (VLac). In contrast, jugular venous oxygen saturation (SjvO2) declined. In the present study, 1H-MRS could be used to quantitatively assess brain injury in terms of microcirculation disorder, oxidative stress, blood-brain barrier disruption, and glial cell activation through changes in metabolites within brain tissue.

Fathers' needs of breastfeeding support: Perspective of health nurses.

PURPOSE: To explore the improvement of health education on father's participation in breastfeeding from the perspective of maternal and child health nurses. METHODS: Qualitative phenomenological research was used, and 15 maternal and child health nurses who provided breastfeeding support were invited. With semi-structured deep interviews and on-site recordings, data were analyzed through content analysis. RESULTS: Four main themes were extracted, including 'cultivating fathers' awareness of participation in breastfeeding', 'collaboration of multiple disciplines to improve health education on breastfeeding for fathers in hospital', 'Simulated scenarios to develop fathers' skills in solving breastfeeding problems', and 'establishing a hospital-community interface network to improve breastfeeding continuation care after hospital discharge'. CONCLUSIONS: Medical and health care departments should attach importance to guidance on health education for fathers' breastfeeding participation, cultivate fathers' awareness of participation in breastfeeding, provide multi-disciplinary collaboration-based health education on breastfeeding for fathers from the prenatal period and improve post-discharge health education on breastfeeding. The additional education being suggested would contribute to fathers being able to play an important role in breastfeeding.

Deletion of the mitochondrial calcium uniporter in adipose tissue promotes energy expenditure and alleviates diet-induced obesity.

OBJECTIVE: Studies have shown a correlation between obesity and mitochondrial calcium homeostasis, yet it is unclear whether and how Mcu regulates adipocyte lipid deposition. This study aims to provide new potential target for the treatment of obesity and related metabolic diseases, and to explore the function of Mcu in adipose tissue. METHODS: We firstly investigated the role of mitoxantrone, an Mcu inhibitor, in the regulation of glucose and lipid metabolism in mouse adipocytes (3T3-L1 cells). Secondly, C57BL/6J mice were used as a research model to investigate the effects of Mcu inhibitors on fat accumulation and glucose metabolism in mice on a high-fat diet (HFD), and by using CRISPR/Cas9 technology, adipose tissue-specific Mcu knockdown mice (Mcufl/+ AKO) and Mcu knockout of mice (Mcufl/fl AKO) were obtained, to further investigate the direct effects of Mcu on fat deposition, glucose tolerance and insulin sensitivity in mice on a high-fat diet. RESULTS: We found the Mcu inhibitor reduced adipocytes lipid accumulation and adipose tissues mass in mice fed an HFD. Both Mcufl/+ AKO mice and Mcufl/fl AKO mice were resistant to HFD-induced obesity, compared to control mice. Mice with Mcufl/fl AKO showed improved glucose tolerance and insulin sensitivity as well as reduced hepatic lipid accumulation. Mechanistically, inhibition of Mcu promoted mitochondrial biogenesis and adipocyte browning, increase energy expenditure and alleviates diet-induced obesity. CONCLUSIONS: Our study demonstrates a link between adipocyte lipid accumulation and mCa2+ levels, suggesting that adipose-specific Mcu deficiency alleviates HFD-induced obesity and ameliorates metabolic disorders such as insulin resistance and hepatic steatosis. These effects may be achieved by increasing mitochondrial biosynthesis, promoting white fat browning and enhancing energy metabolism.

The pan-Canadian Tiered Pricing Framework and Chinese National Volume-Based Procurement: A comparative study using Donabedian's structure-process-outcome framework.

Background: Generic drugs have been seen as a potentially powerful way to alleviate the financial burden on patients and health care systems. Two strategies for achieving rational prices of generic drugs are tiered pricing framework and pooled purchasing power. We compare the pan-Canadian Tiered Pricing Framework (TPF) and the Chinese National Volume-Based Procurement (NVBP) as comparators to explore the similarities and differences between the two mechanisms and summarise lessons for other jurisdictions. Methods: This comparative study applies Donabedian's structure-process-outcome framework to systematically analyse the macro contexts, procedures, and long- and short-term results of each pricing mechanism, and the interactions between them. Results: Structure: TPF is an upstream initiative aimed at lowering the prices of generic drugs and increasing coverage and price consistency. NVBP is a downstream national initiative prioritised for reducing drug prices to achieve value-based purchasing. Process: By associating the number of manufacturers with price cuts, TPF leaves the choice to manufacturers to decide if they want to enter a specific market. In contrast, the Chinese government determines NVBP list and has the authority to choose manufacturer(s) with the lowest price(s). TPF provides clear price information to potential suppliers with unclear order quantity. The NVBP drug price is determined by tendering, while procurement volume is clear and massive. Outcome: The effectiveness of TPF and NVBP is similar, with both achieving a 53% price cut. Both TPF and NVBP experienced efficiency improvement since their establishment, with 98 and 86 drugs priced per year. By comparing 60 drugs covered by both programmes, the NVBP price is 57% of that of the TPF counterpart on average (1.1 to 301.6%), by purchase power parity. Conclusions: The tiered pricing scheme is feasible in regions with a stable and mature pharmaceutical market, typically seen in high-income countries, while tendering is more workable in low- and middle-income countries where the pharmaceutical market is weak and unstable. Experience in the two countries shows that a coordinated pricing mechanism involves many piecemeal interactive problems, which a sophisticated system with a robust long-range plan may address better.

Deep Learning-Based Model for Automatic Assessment of Anterior Angle Chamber in Ultrasound Biomicroscopy.

OBJECTIVE: The goal of the work described here was to develop and assess a deep learning-based model that could automatically segment anterior chamber angle (ACA) tissues; classify iris curvature (I-Curv), iris root insertion (IRI), and angle closure (AC); automatically locate scleral spur; and measure ACA parameters in ultrasound biomicroscopy (UBM) images. METHODS: A total of 11,006 UBM images were obtained from 1538 patients with primary angle-closure glaucoma who were admitted to the Eye Center of Renmin Hospital of Wuhan University (Wuhan, China) to develop an imaging database. The UNet++ network was used to segment ACA tissues automatically. In addition, two support vector machine (SVM) algorithms were developed to classify I-Curv and AC, and a logistic regression (LR) algorithm was developed to classify IRI. Meanwhile, an algorithm was developed to automatically locate the scleral spur and measure ACA parameters. An external data set of 1,658 images from Huangshi Aier Eye Hospital was used to evaluate the performance of the model under different conditions. An additional 439 images were collected to compare the performance of the model with experts. RESULTS: The model achieved accuracies of 95.2%, 88.9% and 85.6% in classification of AC, I-Curv and IRI, respectively. Compared with ophthalmologists, the model achieved an accuracy of 0.765 in classifying AC, I-Curv and IRI, indicating that its high accuracy was as high as that of the ophthalmologists (p > 0.05). The average relative errors (AREs) of ACA parameters were smaller than 15% in the internal data sets. Intraclass correlation coefficients (ICCs) of all the angle-related parameters were greater than 0.911. ICC values of all iris thickness parameters were greater than 0.884. The accurate measurement of ACA parameters partly depended on accurate localization of the scleral spur (p < 0.001). CONCLUSION: The model could effectively and accurately evaluate the ACA automatically based on fully automated analysis of UBM images, and it can potentially be a promising tool to assist ophthalmologists. The present study suggested that the deep learning model can be extensively applied to the evaluation of ACA and AC-related biometric risk factors, and it may broaden the application of UBM imaging in the clinical research of primary angle-closure glaucoma.

Heterogeneity of financial toxicity and associated risk factors for older cancer survivors in China.

In China, older cancer survivors may show heterogeneity in financial toxicity (FT). We aimed to identify FT profiles among older Chinese cancer survivors and examine the association between FT profiles and individual characteristics. We used a latent profile analysis to categorize participants and a multinomial logistic regression to examine the associations. We identified three distinct FT profiles: high, moderate, and low. Participants aged 65-69 years, with a monthly household income ≥ 5,000 CNY and a high school education or above were more likely to be classified into the moderate than high FT profile, a monthly household income ≥ 5,000 CNY increased the likelihood of being in the low FT profile and living alone negatively affected the odds of being in the low FT profile. The findings identified heterogeneity in FT among this population, may help identify high-risk groups, and may enable early intervention.

Subjective and objective analysis of orthodontic expert consensus on the assessment of orthodontic treatment outcomes.

OBJECTIVE: The objective of the study was to explore and validate the consensus of orthodontic experts on the assessment of orthodontic treatment outcomes based on subjective and objective analysis. MATERIALS AND METHODS: The research consisted of two parts: the exploration and verification of expert consensus. First, a sample of 108 cases randomly selected from six dental schools in China were evaluated by 69 orthodontic experts and measured by researchers based on post-treatment study casts and lateral cephalograms, respectively. Then, through statistical analysis, the objective indicators significantly correlated with experts' subjective evaluations were selected, their weights were determined, and the critical values of satisfactory, acceptable and unacceptable grades were screened. Subsequently, another sample of 72 cases were evaluated by another 36 orthodontic experts, and the subjective evaluation results were compared with the objective measurement results. RESULTS: There were six model indicators and seven cephalometric indicators being significantly correlated with the experts' subjective evaluations, including occlusal contact, overjet, midline, interproximal contact, alignment, occlusal relationship, L1/NB, ANB, SN/OP, U1/SN, LL-EP, Cm-Sn-UL and Ns-Prn-Pos, with a cumulative R2 of 0.704. In the verification part, the correlation coefficient between the 36 experts' subjective scores and objective regression scores was 0.716 (P < .001); the correlation coefficient between the 36 experts' subjective grades and objective grades was 0.757 (P < .001). CONCLUSIONS: Orthodontic experts had good consistency in the subjective evaluation of the combined records of post-treatment study casts and lateral cephalograms. The objective indicators selected from subjective and objective analysis had good reliability and validity and could further improve the existing occlusal indices.

Salient Region Guided Blind Image Sharpness Assessment.

Salient regions provide important cues for scene understanding to the human vision system. However, whether the detected salient regions are helpful in image blur estimation is unknown. In this study, a salient region guided blind image sharpness assessment (BISA) framework is proposed, and the effect of the detected salient regions on the BISA performance is investigated. Specifically, three salient region detection (SRD) methods and ten BISA models are jointly explored, during which the output saliency maps from SRD methods are re-organized as the input of BISA models. Consequently, the change in BISA metric values can be quantified and then directly related to the difference in BISA model inputs. Finally, experiments are conducted on three Gaussian blurring image databases, and the BISA prediction performance is evaluated. The comparison results indicate that salient region input can help achieve a close and sometimes superior performance to a BISA model over the whole image input. When using the center region input as the baseline, the detected salient regions from the saliency optimization from robust background detection (SORBD) method lead to consistently better score prediction, regardless of the BISA model. Based on the proposed hybrid framework, this study reveals that saliency detection benefits image blur estimation, while how to properly incorporate SRD methods and BISA models to improve the score prediction will be explored in our future work.

Status, fuzzy integrated risk assessment, and hierarchical risk management of soil heavy metals across China: A systematic review.

Many reviewers have applied bibliometric analysis to conduct research on heavy metals (HMs) in Chinese soil and found that risk management decisions were biased to a certain extent due to case distribution difference and uncertainty. The previous methodologies were optimized integrating further uncertainty control and case identification in this study. A solid database was built, which included 779 cases published from 2009 to 2020. Based on the data features, the weight method was used to objectively shield extreme cases and normalize the concentrations. We conducted fuzzy eco- and health risk models via a triangular fuzzy number, and identified the risks from Pb, Cd, As, and Hg as the priority control metals. However, the national HMs risk had complex spatial heterogeneity and significant uncertainty. Thus, an "integrated risk grade criterion (IRGC)" was coupled with the risk threshold concentrations for the eco- and health risks to classify the each case. The cases above the moderate IRGC grade for Cd or Hg accounted for approximately 50%, and were mainly in the west and north of China, respectively. The high-grade areas were mostly in the south of China, including the Xijiang-Pearl River Basin and the Yangtze River Basin. It was demonstrated that warning health risks were likely a local question and that the ecological risks from Hg and Cd were considerable across China. By reviewing and summarizing the text information, high grades of soil Cd, Pb, and As were frequently reported in the villages associated with the mining industry, and certain soil Cd near suburban industrial complexes also caused warning health risks. Finally, this study proposed priority control objects for hierarchical risk management, including the identified heavy metals, areas, and pilot cities from multi-spatial scales.

Socioeconomic disparities in psychological health: Testing the Reserve Capacity Model in a population-based sample of Chinese migrants.

Based on the Reserve Capacity Model, this study investigated the associations of objective socioeconomic status and subjective social status with psychological health and the underlying psychosocial mechanisms in a population-based sample of Chinese migrants (n = 15,999). Results showed that subjective social status was positively associated with life satisfaction and self-rated health through the mediation of psychological distress and perceived stress. Whereas education showed a very weak association with life satisfaction, income was directly associated with life satisfaction only. The findings suggest that reducing psychosocial vulnerabilities may be a potential impetus to eliminate socioeconomic health disparities among Chinese migrants.

An Ecological Study of Tuberculosis Incidence in China, From 2002 to 2018.

INTRODUCTION: Tuberculosis is one of the main infectious diseases threatening global health, which is also the main cause of death from a single source of infection (above HIV/AIDS). China is a country with a high burden of tuberculosis in the world, ranking only behind India and Indonesia. However, there are few ecological studies on the burden of tuberculosis in China. This study aims to provide more research basis for the government to formulate tuberculosis policies by exploring the ecological factors associated with the incidence of tuberculosis, so as to achieve the goal of eliminating tuberculosis by 2030. METHODS: We collected data on the incidence of tuberculosis and ecological factors of 31 provinces, autonomous regions, and municipalities in Mainland China (excluding Taiwan, Hong Kong, and Macau) from 2002 to 2018. We constructed a framework of ecological factors affecting the incidence, which consists of 5 secondary indicators and 35 tertiary indicators. And we construct a dynamic panel data model based on the Lasso Regression to select variables to test the effect of each ecological factor on the incidence. RESULTS: Among the 35 tertiary indicators, economy 3,4,6,7, environment 1, recourses 1,3, demography 3, and lifecare 2,4,8,9,13 passed the significance test at the 1% level, economy 1,2,5, environment 2,9, lifecare 6,12 passed the significance test at the 5% level, lifecare 10 passed the significance test at the 10% level. Only economy 5 and economy 6 have a positive impact on the incidence, other statistically significant ecological indicators are negatively correlated with the incidence. CONCLUSIONS: Our study indicated that many ecological factors, including residents' income, unemployment rate, educational level, medical resources, population density, sunshine duration and dietary structure, are closely related to the incidence of tuberculosis. These findings contribute the government to taking targeted measures for tuberculosis prevention and control, including improving the level of economic development, increasing employment, expanding the scale of enrollment in colleges and universities, and ensuring that the prices of sources of animal protein are reasonable to meet the residents' intake of protein.

Fuzzy health risk assessment and integrated management of toxic elements exposure through soil-vegetables-farmer pathway near urban industrial complexes.

Urban industrial areas were being built globally, which decreased key geographical separation between agriculture and industrial areas, especially in developing countries. Now, limited studies concerned coordinated the vegetables and soil management for toxic elements (TEs) in this mixed land system. To fill this gap, an integrated environmental multi-media risk management method was explored based on laboratory analysis, health risk assessment, uncertainty control, and source apportionment. The Chinese Beihu area of Wuhan City was selected as a typical case and the measurements of Zn, Cr, Cu, Pb, As, and Cd in soil revealed that TEs pollution was slight and concentrations met the Chinese standards. Meanwhile, some vegetables exceeded corresponding standard limits. To further quantify negative health effects posed by the studied TEs both in soils and vegetables, an established fuzzy health risk assessment for farmers was employed and the results indicated that the soil exposure of As and the vegetable consumption needed the priority control. The carcinogenic risk (CR) of As in soil was [4.60E-6, 1.45E-5] and the cumulative CR (sum of CRAs, CRPb and CRCd) in leafy vegetables was [1.08E-4, 1.38E-4], which was higher than that of the other vegetables. Preventing soil oral exposure and reducing self-grown vegetable consumption (30%-50%) were proven as effective risk interventions via uncertainty control methods. Spatially, the risk grades under maximum membership principle decreased from south to north in the Beihu area, and the south area was identified as the priority control area. Source apportionment identified four source patterns (Zn-Cr-Cu, Pb, As, and Cd) for soil, and the probable bioaccumulation mechanisms for leafy vegetables by multivariate statistical analyses. Finally, the integrated management strategies were formulated from perspectives of the risk sources, exposure pathways and the scenario.

Heavy metal pollution and ecological risk assessment in brownfield soil from Xi'an, China: An integrated analysis of man-land interrelations.

The core of urbanization is land use change, resulting in the urban sprawl and urban population explosion. The problem of land resources shortage and ecological environment destruction has become increasingly prominent. Land use change and human activities can directly lead to urban soil pollution. This study analyzed the concentration of Cd, Cr, Cu, Ni, Pb, Zn, Hg and As in the original site of Xi'an chlor-alkali chemical plant, which was know as a brownfield. The results showed the concentrations of Hg, Pb and Zn in research areas were obviously higher than soil background value. Through pollution index (PI) method and Geo-accumulation Index (Igeo) method, totally 26 sample points in different areas (A, B, C, D) were classified into different pollution degrees. The CPI results indicated 9 sample points were heavily polluted, accounting for 34.6% of the total. Among them, 6 out of 9 were located in area A. 12 samples points were not polluted. The average Igeo values of single heavy metal were arranged in the order of Hg (1.83) > Zn (1.26) > Pb (0.33). The pollution of Hg was relatively serious and extensive, especially in area A. It was mainly because of the historical pollution produced by chemical plant. The pollution of Pb in each point was quite different. Mainly influenced by automobile related activities, Igeo(Pb) in sample point 15 and 16 were all beyond 4.00. The average potential ecological risk (PER) of each area was in the order of A (1428) > B (297) > D (249) > C (163). The ecological risk was mainly determined by previous industrial production and present human activity at the same time. People and land are interdependent and interactive. The understanding on the mechanism of man-land interralations, regarding to urban land use and ecological environment, will promote urban sustainability.

Association between economic development level and tuberculosis registered incidence in Shandong, China.

BACKGROUND: Tuberculosis (TB) is one of the major infectious diseases that seriously endanger people's health. In Shandong province, the relationship between the level of economic development and TB incidence has not been studied. This study aims to provide more research basis for the government to prevent and control TB by exploring the impact of different economic factors on TB incidence. METHODS: By constructing threshold regression model (TRM), we described the extent to which different economic factors contribute to TB registered incidence and differences in TB registered incidence among seventeen cities with different levels of economic development in Shandong province, China, during 2006-2017. Data were retrieved from the China Information System for Disease Control and Prevention. RESULTS: Per capita medical expenditure (regression coefficient, -0.0314462; SD, 0.0079305; P > |t|, 0.000) and per capita savings (regression coefficient, 0.0001924; SD, 0.0000566; P > |t|, 0.001) passed the significance test at the level of 1%.They are the two economic indicators that have the greatest impact on TB registered incidence. Through the threshold test, we selected the per capita savings as the threshold variable. In the three stages of per capita savings (<9772.8086 China Yuan(CNY); 9772.8086-33,835.5391 CNY; >33,835.5391 CNY), rural per capita income always has a significant negative impact on the TB registered incidence (The regression coefficients are - 0.0015682, - 0.0028132 and - 0.0022253 respectively. P is 0.007,0.000 and 0.000 respectively.).In cities with good economies, TB registered incidence was 38.30% in 2006 and dropped to 25.10% by 2017. In cities with moderate economies, TB registered incidence peaked in 2008 at 43.10% and dropped to 27.1% by 2017.In poorer cities, TB registered incidence peaked in 2008 at 56.30% and dropped to 28.9% in 2017. CONCLUSION: We found that per capita savings and per capita medical expenditure are most closely related to the TB incidence. Therefore, relevant departments should formulate a more complete medical system and medical insurance policy to effectively solve the problem of "difficult and expensive medical treatment". In order to further reduce the TB incidence, in addition to timely and accurate diagnosis and treatment, it is more important for governments to increase investment in medicine and health care.

Electrochemical treatment of flutriafol wastewater using a novel 3D macroporous PbO2 filter: Operating parameters, mechanism and toxicity assessment.

In order to break the high operating cost bottleneck of electrochemical treatment of aqueous flutriafol (FTF), an emerging fungicide, a novel three-dimensional ordered macroporous PbO2 (3DOM-PbO2) filter was designed to facilitate mass transfer. The effects of operating parameters, including current density, flow rate and initial concentration on FTF electrooxidation performance were investigated using conventional flat Ti/PbO2 (F-Ti/PbO2) and 3DOM-PbO2 filters, with primary objective being the development of appropriate parameters for FTF treatment. The results indicated that the FTF removal efficiency on 3DOM-PbO2 filter was improved by 2.8 times compared to that on F-Ti/PbO2 at 5 mA cm-2, 10 ml s-1 and 100 mg L-1 FTF. The corresponding electrical energy consumption was reduced by 2.7 times, ` TOC removal and mineralization current efficiency were enhanced by 4.9 and 4.8 times, respectively. Furthermore, aromatic intermediates, nitrogenous compounds and carboxylic acids were identified as main byproducts using experimental method combined with quantum chemical calculations. Then, a possible pathway of FTF degradation on 3DOM-PbO2 was proposed. Finally, the acute toxicity results showed that toxicity of the byproducts first increases and then decreases through the proposed route. LC50,48 h value of FTF wastewater increased 35%-70% on the 3DOM-PbO2 filter, indicating a significant biodegradability enhancement.

Interpreting weightings of the peer assessment rating index and the discrepancy index across contexts on Chinese patients.

Objective: Determine optimal weightings of Peer Assessment Rating (PAR) index and Discrepancy Index (DI) for malocclusion severity assessment in Chinese orthodontic patients. Methods: Sixty-nine Chinese orthodontists assessed a full set of pre-treatment records from a stratified random sample of 120 subjects gathered from six university orthodontic centres. Using professional judgment as the outcome variable, multiple regression analyses were performed to derive customized weighting systems for the PAR index and DI, for all subjects and each Angle classification subgroup. Results: Professional judgment was consistent, with an Intraclass Correlation Coefficient (ICC) of 0.995. The PAR index or DI can be reliably measured, with ICC = 0.959 and 0.990, respectively. The predictive accuracy of PAR index was greatly improved by the Chinese weighting process (from r = 0.431 to r = 0.788) with almost equal distribution in each Angle classification subgroup. The Chinese-weighted DI showed a higher predictive accuracy, at P = 0.01, compared with the PAR index (r = 0.851 versus r = 0.788). A better performance was found in the Class II group (r = 0.890) when compared to Class I (r = 0.736) and III (r = 0.785) groups. Conclusions: The Chinese-weighted PAR index and DI were capable of predicting 62 per cent and 73 per cent of total variance in the professional judgment of malocclusion severity in Chinese patients. Differential prediction across Angle classifications merits attention since different weighting formulas were found.

Multi-laboratory assessment of reproducibility, qualitative and quantitative performance of SWATH-mass spectrometry.

Quantitative proteomics employing mass spectrometry is an indispensable tool in life science research. Targeted proteomics has emerged as a powerful approach for reproducible quantification but is limited in the number of proteins quantified. SWATH-mass spectrometry consists of data-independent acquisition and a targeted data analysis strategy that aims to maintain the favorable quantitative characteristics (accuracy, sensitivity, and selectivity) of targeted proteomics at large scale. While previous SWATH-mass spectrometry studies have shown high intra-lab reproducibility, this has not been evaluated between labs. In this multi-laboratory evaluation study including 11 sites worldwide, we demonstrate that using SWATH-mass spectrometry data acquisition we can consistently detect and reproducibly quantify >4000 proteins from HEK293 cells. Using synthetic peptide dilution series, we show that the sensitivity, dynamic range and reproducibility established with SWATH-mass spectrometry are uniformly achieved. This study demonstrates that the acquisition of reproducible quantitative proteomics data by multiple labs is achievable, and broadly serves to increase confidence in SWATH-mass spectrometry data acquisition as a reproducible method for large-scale protein quantification.SWATH-mass spectrometry consists of a data-independent acquisition and a targeted data analysis strategy that aims to maintain the favorable quantitative characteristics on the scale of thousands of proteins. Here, using data generated by eleven groups worldwide, the authors show that SWATH-MS is capable of generating highly reproducible data across different laboratories.

Assessment of immunoreactive synthetic peptides from the structural proteins of severe acute respiratory syndrome coronavirus.

BACKGROUND: The widespread threat of severe acute respiratory syndrome (SARS) to human life has spawned challenges to develop fast and accurate analytical methods for its early diagnosis and to create a safe antiviral vaccine for preventive use. Consequently, we thoroughly investigated the immunoreactivities with patient sera of a series of synthesized peptides from SARS-coronavirus structural proteins. METHODS: We synthesized 41 peptides ranging in size from 16 to 25 amino acid residues of relatively high hydrophilicity. The immunoreactivities of the peptides with SARS patient sera were determined by ELISA. RESULTS: Four epitopic sites, S599, M137, N66, and N371-404, located in the SARS-coronavirus S, M, and N proteins, respectively, were detected by screening synthesized peptides. Notably, N371 and N385, located at the COOH terminus of the N protein, inhibited binding of antibodies to SARS-coronavirus lysate and bound to antibodies in >94% of samples from SARS study patients. N385 had the highest affinity for forming peptide-antibody complexes with SARS serum. CONCLUSIONS: Five peptides from SARS structural proteins, especially two from the COOH terminus of the N protein, appear to be highly immunogenic and may be useful for serologic assays. The identification of these antigenic peptides contributes to the understanding of the immunogenicity and persistence of SARS coronavirus.