Sensitive, precise fingerprint profiling for monosaccharide analysis of Bacillus Calmette-Guérin polysaccharide and nucleic acid isolates.

A sensitive and precise HPLC-DAD method with pre-column PMP derivatization was established and validated, for analyzing the polysaccharides in Bacillus Calmette-Guérin polysaccharide and nucleic acid (BCG-PSN) isolates, after acid hydrolysis. And the HPLC fingerprint profiling was used to analyze its monosaccharide composition. The monosaccharide concentration-peak area calibration curve was of good linearity (R2 > 0.99), over the range of 0.016-0.08 mg/mL for mannose or 0.24-1.20 mg/mL for glucose, with high recovery of 93-105 % for quality control samples. The intra-day RSD values of mannose and glucose concentration were less than 2.5 % and 2.1 %, respectively, and their inter-day RSD values were less than 4.3 % and 2.2 %, respectively, and remained stable for up to 14 days. This method also remained durable against changes in chromatographic parameters, but it's susceptible to the flow rate of mobile phase. Additionally, the method was applied to analyze the content of mannose and glucose in 22 batches BCG-PSN powder and 17 batches BCG-PSN injection. The results showed that the HPLC-DAD fingerprint spectra of all the BCG-PSN powder and BCG-PSN injection samples had a high degree of similarity, with the similar indexes up to 0.999 and 0.998, respectively. The HPLC-DAD method with pre-column PMP derivatization is highly rapid, effective, visual, and accurate for determination of monosaccharide contents. The validated method was successfully applied to the analysis of polysaccharide in both BCG-PSN powder and injection.

Aberrant dynamic functional network connectivity in progressive supranuclear palsy.

BACKGROUND: The clinical symptoms of progressive supranuclear palsy (PSP) may be mediated by aberrant dynamic functional network connectivity (dFNC). While earlier research has found altered functional network connections in PSP patients, the majority of those studies have concentrated on static functional connectivity. Nevertheless, in this study, we sought to evaluate the modifications in dynamic characteristics and establish the correlation between these disease-related changes and clinical variables. METHODS: In our study, we conducted a study on 53 PSP patients and 65 normal controls. Initially, we employed a group independent component analysis (ICA) to derive resting-state networks (RSNs), while employing a sliding window correlation approach to produce dFNC matrices. The K-means algorithm was used to cluster these matrices into distinct dynamic states, and then state analysis was subsequently employed to analyze the dFNC and temporal metrics between the two groups. Finally, we made a correlation analysis. RESULTS: PSP patients showed increased connectivity strength between medulla oblongata (MO) and visual network (VN) /cerebellum network (CBN) and decreased connections were found between default mode network (DMN) and VN/CBN, subcortical cortex network (SCN) and CBN. In addition, PSP patients spend less fraction time and shorter dwell time in a diffused state, especially the MO and SCN. Finally, the fraction time and mean dwell time in the distributed connectivity state (state 2) is negatively correlated with duration, bulbar and oculomotor symptoms. DISCUSSION: Our findings were that the altered connectivity was mostly concentrated in the CBN and MO. In addition, PSP patients had different temporal dynamics, which were associated with bulbar and oculomotor symptoms in PSPRS. It suggest that variations in dynamic functional network connectivity properties may represent an essential neurological mechanism in PSP.

Person re-identification based on multi-branch visual transformer and self-distillation.

Person re-identification technology has made significant progress in recent years with the development of deep learning. However, the recognition rate of models in this field is still lower than that of face recognition, which is challenging to implement in practical application scenarios. Therefore, improving the recognition rate of the pedestrian re-identification model is still a critical task. This paper mainly focuses on three aspects of this problem. The first is to use the characteristics of the multi-branch network structure of person re-identification to dig out the most effective online self-distillation scheme between branches without increasing additional resource requirements, making full use of the information contained in each branch. Secondly, this paper analyzes and verifies the pros and cons of knowledge distillation based on mean squared error (MSE) loss function and Kullback-Leibler (KL) divergence from theoretical and experimental perspectives. Finally, we verified through experiments that adding a specific value of noise perturbation to the model weights can further improve the recognition rate of the model. After several improvements in these areas, we obtained the current state-of-the-art performance on four public datasets for person re-identification.

SMAD7 gene polymorphisms and their influence on patients with colorectal cancer.

Colorectal cancer (CRC) is a prevalent malignant tumor, and its pathogenesis is still not fully understood. Studies have shown that SMAD7 gene polymorphisms can affect CRC susceptibility, but the results have been inconsistent and require additional confirmation. Our study aimed to evaluate the effect of SMAD7 variants on the risk of CRC in the Chinese Han population. A total of five single nucleotide polymorphisms (SNPs) in SMAD7 were genotyped among 696 CRC patients and 696 healthy participants using the MassARRAY iPLEX platform. SNPs were evaluated for their associations with CRC using logistic regression analysis under multiple genetic models. The false-positive report probability (FPRP) analysis was used to validate the positive findings. Our study indicated that rs11874392 showed an increased association with CRC risk (odds ratio, 1.31; 95% confidence interval, 1.04-1.67; p = 0.024). Stratified analysis showed that rs11874392 might increase the risk of CRC in females (OR = 1.70, p = 0.028), individuals with smoking (OR = 1.87, p = 0.026), and drinking (OR = 1.38, p = 0.027). The rs11874392 was found to be related to an elevated risk of rectal cancer (OR = 1.73, p = 0.003), but not with colon cancer. FPRP analysis demonstrated that all of these associations were statistically significant (FPRP <0.2). Additionally, rs11874392 was the strongest predictive model for CRC. This study provides evidence that the SMAD7 rs11874392 is related to an increased susceptibility to CRC.

Simulation insights into the lipase adsorption on zeolitic imidazolate framework-8.

Zeolitic imidazolate frameworks (ZIFs) have recently emerged as immobilization matrices for biomolecules, most notably enzymes. Understanding the key factors that dominate the enzyme's catalytic activity on/in ZIFs is crucial for the development of new immobilization matrices. In this work, a combination of the parallel tempering Monte Carlo simulation and all-atom molecular dynamics simulation is performed to study the orientation and conformation of the Candida rugose lipase (CRL) adsorbed on oppositely charged and neutral ZIF-8 (i.e., ZIF-8-COOH, ZIF-8-NH2, and ZIF-8-neutral) surfaces. The results show that CRL could adsorb on all ZIF-8 surfaces, with an ordered orientation obtained on charged ZIF-8 surfaces. ZIF-8-NH2 is a good candidate for CRL immobilization since it can maximize the catalytic activity of CRL. The native conformation of CRL is well preserved on all three surfaces due to the partially water-containing surface of ZIF-8. The results could provide theoretical support for the application of porous materials in enzyme immobilization.

Dynamic cytokines signature predicts survival outcome from severe Immune-related hepatitis with PD-1/PD-L1 blockade in lung cancer.

BACKGROUND: Immune-related adverse events (irAEs), particularly immune-related hepatitis (IRH) is a potentially serious complication of immune checkpoint inhibitor (ICI) therapy. This retrospective cohort study investigated potential prognostic and predictive biomarkers for IRH. METHOD: This study included 37 patients with advanced lung cancer who received ICIs and were divided into two groups: ≥Grade 3 (G3)-IRH group (n = 17) and without irAE (no-irAE) group (n = 20). Blood samples collected at three different time points and pre-treatment tumor biopsy samples were analyzed using multi-omics assays. RESULTS: The IL-1B RNA expression was significantly increased (limma, fold = 1.94) in the ≥ G3-IRH group than the no-irAE group. Compared with no-irAE group, ≥G3-IRH group had higher monocyte and eosinophil infiltration and lower macrophage infiltration, particularly macrophage M2. Transcriptomics analyses of pre-treatment tumor samples revealed significant upregulation of various inflammation-related genes in the ≥ G3-IRH group (False discovery rate < 0.05). Moreover, various proinflammatory cytokines and chemokines were significantly lower in the plasma of the ≥ G3-IRH group than in the no-irAE group. Subgroup analyses of the ≥ G3-IRH group revealed that plasma IL-1A was significantly higher among those whose IRH resolved than those who had IRH-related death. Patients who died had a greater increase in immune score and Euclidean distance from the baseline to the seventh day of IRH onset, with a dramatic increase in Euclidean distance after immunosuppression, suggesting overstimulated immune status. CONCLUSION: Our study demonstrated the association between IL-1B overexpression and IRH susceptibility. Immune score and Euclidean distance of inflammatory cytokines may provide predictive value on the survival outcome from ≥ G3 IRH.

Adverse short-term effects of ozone on cardiovascular mortalities modified by season and temperature: a time-series study.

Introduction: Ambient ozone pollution becomes critical in China. Conclusions on the short-term effects of ozone on cardiovascular mortality have been controversial and limited on cause-specific cardiovascular mortalities and their interactions with season and temperature. This research aimed to investigate the short-term effects of ozone and the modifications of season and temperature on cardiovascular mortality. Methods: Cardiovascular death records, air pollutants, and meteorological factors in Shenzhen from 2013 to 2019 were analyzed. Daily 1-h maximum of ozone and daily maximum 8-h moving average of ozone were studied. Generalized additive models (GAMs) were applied to evaluate their associations with cardiovascular mortalities in sex and age groups. Effect modifications were assessed by stratifying season and temperature. Results: Distributed lag impacts of ozone on total cardiovascular deaths and cumulative effects on mortality due to ischemic heart disease (IHD) were most significant. Population under 65 years old was most susceptible. Majority of significant effects were found in warm season, at high temperature, and at extreme heat. Ozone-associated risks in total deaths caused by hypertensive diseases reduced in warm season, while risks in IHD in males increased at high temperature. Extreme heat enhanced ozone effects on deaths caused by CVDs and IHD in the population under 65 years old. Discussion: The revealed cardiovascular impacts of ozone below current national standard of air quality suggested improved standards and interventions in China. Higher temperature, particularly extreme heat, rather than warm season, could significantly enhance the adverse effects of ozone on cardiovascular mortality in population under 65 years old.

A novel biological sources consistency evaluation method reveals high level of biodiversity within wild natural medicine: A case study of Amynthas earthworms as "Guang Dilong".

For wild natural medicine, unanticipated biodiversity as species or varieties with similar morphological characteristics and sympatric distribution may co-exist in a single batch of medical materials, which affects the efficacy and safety of clinical medication. DNA barcoding as an effective species identification tool is limited by its low sample throughput nature. In this study, combining DNA mini-barcode, DNA metabarcoding and species delimitation method, a novel biological sources consistency evaluation strategy was proposed, and high level of interspecific and intraspecific variations were observed and validated among 5376 Amynthas samples from 19 sampling points regarded as "Guang Dilong" and 25 batches of proprietary Chinese medicines. Besides Amynthas aspergillum as the authentic source, 8 other Molecular Operational Taxonomic Units (MOTUs) were elucidated. Significantly, even the subgroups within A. aspergillum revealed here differ significantly on chemical compositions and biological activity. Fortunately, this biodiversity could be controlled when the collection was limited to designated areas, as proved by 2796 "decoction pieces" samples. This batch biological identification method should be introduced as a novel concept regarding natural medicine quality control, and to offer guidelines for in-situ conservation and breeding bases construction of wild natural medicine.

Effects of Bacterial Biofilm on Regulation of Neurovascular Unit Functions and Neuroinflammation of Patients with Ischemic Cerebral Stroke by Immunocyte.

In this experiment, the effects of biofilm on neurovascular unit functions and neuroinflammation of patients with ischemic cerebral stroke were investigated. For this purpose, 20 adult male rats were purchased from Taconic (8 to 10 weeks old, weighing between 20 and 24g) and selected as the research objects. Then, they were randomly divided into an experimental group (10 rats) and a control group (10 rats). Ischemic cerebral stroke rat models were established. Besides, pseudomonas aeruginosa (PAO1) was prepared manually and implanted into the bodies of rats in the experimental group. mNSS scores, cerebral infarction area, and the release of inflammatory cytokines of rats in the two groups were compared. Results showed that mNSS scores for rats in the experimental group at all periods were remarkably higher than those for rats in the control group (P<0.05), which demonstrated that the rats in the experimental group suffered much severer neurological impairment than those in the control group. In addition, the release of tumor necrosis factor (TNF)-α, interleukin (IL)-6, IL-1ß, inducible nitric oxide synthase (iNOS), and IL-10 were all higher than those of the control group (P<0.05). The cerebral infarction area of the experimental group at all periods was remarkably larger than that of the control group (P<0.05). In conclusion, the formation of biofilm led to the aggravation of neurological impairment and inflammatory reactions among patients with ischemic cerebral stroke.

Detailed Structural Analysis of the Immunoregulatory Polysaccharides from the Mycobacterium Bovis BCG.

Bacillus Calmette-Guérin polysaccharide and nucleic acid (BCG-PSN), extracted from Mycobacterium bovis, is an immunoregulatory medicine commonly used in clinic. However, the structural characteristics and potential pharmacological efficacy of the polysaccharides from BCG-PSN remain unclear. Herein, two polysaccharides (BCG-1 and BCG-2) were purified and their structures were characterized. Monosaccharide composition analysis combined with methylation analysis and NMR data indicated that BCG-1 and BCG-2 were an α-D-(1→4)-mannan with (1→2)-linked branches, and an α-D-(1→4)-glucan with (1→6)-linked branches, respectively. Herein, the mannan from BCG-PSN was first reported. Bioactivity assays showed that BCG-1 and BCG-2 dose-dependently and potently increased the production of inflammatory mediators (NO, TNF-α, IL-6, IL-1ß, and IL-10), as well as their mRNA expressions in RAW264.7 cells; both have similar or stronger effects compared with BCG-PSN injection. These data suggest that BCG-1 and BCG-2 are very likely the active ingredients of BCG-PSN.

Applying finite-time lyapunov exponent to study the tidal dispersion on oil spill trajectory in Burrard Inlet.

This study used a combination of Finite-Time Lyapunov Exponent (FTLE) values, residual currents, and tidal excursion lengths to systematically investigate the effects of tidal dispersion on oil spill trajectories in Burrard Inlet, BC, Canada, which is a tidally dominated estuary. The FTLE analysis results showed that tidal type and tidal phase significantly influenced the FTLE fields because the flow structure and the location of saddle points varied as a function of the tidal type and tidal phase. Some transport barriers formed in the Inner Harbour, which blocked the water exchange between the western and eastern parts of the inlet. Moreover, tidal mixing in the wider regions of Burrard Inlet (i.e., the western Outer Harbour) was relatively weak than in the narrower areas (i.e., First Narrows and Second Narrows). The observations from the FTLE analysis agreed well with the residual currents and tidal excursion results. The drifter trajectories were consistent with the Lagrangian coherent structure lines extracted from the FTLE analysis. To verify the tidal dispersion impact on an oil spill trajectory in the inlet, the FTLE fields were compared with a real oil spill that occurred in Burrard Inlet in 2015 (the M/V Marathassa oil spill). The FTLE fields reasonably explained the spilled oil's trajectories from the real event. In addition, a set of stochastic oil spill models were run in this study and found that the FTLE analysis was a reliable tool for oil spill tracking. Overall, the FTLE method would be a valuable addition to practical oil spill response planning.

Arctiin elevates osteogenic differentiation of MC3T3-E1 cells by modulating cyclin D1.

Osteoporosis is a systemic disorder of bone metabolism. This study aimed to investigate the impacts and possible mechanisms of Arctiin, a lignin isolated from Arctium lappa on MC3T3-E1 osteoblast differentiation. In this study, after treatment with different concentrations of Arctiin, reverse transcription-quantitative polymerase chain reaction (RT-qPCR) and western blotting were used to estimate the expression of osteogenesis markers. Then, the activity of alkaline phosphatase (ALP) was detected by an ALP assay kit and calcium nodules staining was evaluated by alizarin red staining (ARS). Additionally, the regulatory effects of Arctiin on cyclin D1 (Ccnd1) was assessed by measurement of protein expression. Subsequently, the functions of Ccnd1 silencing on the osteogenic differentiation was examined in Arctiin-treated MC3T3-E1 cells. Results indicated that Arctiin dose-dependently upregulated the expression of runt-related transcription factor 2 (RUNX2), collagen type 1 (COL1A1), osteocalcin (OCN) and osteopontin (OPN). Elevated ALP activity and calcification degree was prominently observed in the Arctiin-treated groups. Moreover, Ccnd1 expression was notably enhanced after Arctiin intervention. Importantly, Ccnd1-knockdown abrogated the impacts of Arctiin on osteogenic differentiation of MC3T3-E1. To conclude, findings in this study suggested that Arctiin could regulate MC3T3-E1 osteoblast differentiation via up-regulating Ccnd1, supporting that Arctiin might be a therapeutic target for osteoporosis.

Evaluations of Spatial Accessibility and Equity of Multi-Tiered Medical System: A Case Study of Shenzhen, China.

The Chinese government has implemented a medical system reform to improve the equity of healthcare resources since 2009. We selected Shenzhen as our study area and evaluated the accessibility and equity of the multi-tiered medical system in China using a novel multi-tiered two-step floating catchment area (MT2SFCA) method. We proposed the benchmark and applied the independent variables of travel time and facility attractiveness, along with a combination of the two factors, as tolerances to determine the new logistic cumulative distribution decay functions. Community health centers (CHCs) and hospitals were included while integrating their features. Results revealed that the MT2SFCA method was able to determine the particular advantages of CHCs and hospitals in the multi-tiered medical system. The CHCs offset the lower accessibility of hospitals in suburban areas and hospitals balanced the regional inequity caused by the CHC. Travel time is the main consideration of patients who have access to CHCs, whereas facility features are the main considerations of patients who have access to hospitals. Notably, both CHCs and hospitals are crucial for the whole multi-tiered medical system. Finally, we suggested modifications in different travel modes, weights of contributing factors, and the validation of decay functions to improve the MT2SFCA method.

Shuxuetong injection and its peptides enhance angiogenesis after hindlimb ischemia by activating the MYPT1/LIMK1/Cofilin pathway.

ETHNOPHARMACOLOGICAL RELEVANCE: Shuxuetong (SXT) injection is formulated by leech and earthworm, has been widely used in the treatment of thrombotic cardiovascular and cerebrovascular diseases with remarkable clinical efficacy. AIM OF THE STUDY: The purpose of this study is to investigate the protective mechanism of SXT injection on the mice model of hindlimb ischemia, and to evaluate the angiogenic effects of SXT injection and its main active substances. MATERIALS AND METHODS: Hindlimb ischemia was induced by left femoral artery ligation. After operation, the mice were injected with saline, 10 mg/kg/d cilostazol, 37.5 mg/kg/d SXT injection, 75 mg/kg/d SXT injection and 150 mg/kg/d SXT injection via tail vein for 4 weeks. Ischemia severity was assessed using laser Doppler perfusion imaging system. Tissue recovery and capillary density were evaluated by histological and immunofluorescent staining. Vascular endothelial growth factor-A (VEGF-A) and platelet-derived growth factor (PDGF-BB) expression were measured by reverse transcription polymerase chain reaction (RT-PCR) and enzyme-linked immunosorbent assay (ELISA) analyses. Human umbilical vein endothelial cells (HUVECs) proliferation was measured using a BrdU kit and the viability of HUVECs was performed by MTT assay. Migration of HUVECs was performed by the wound healing method and a modified transwell assay. Capillary tube formation by HUVECs was examined by using Matrigel assay. Western blotting was used to detect the expressions of p-Cofilin, p-MYPT1, and p-LIMK1. RESULTS: SXT injection treatment significantly restored the blood flow and reduced tissue injury in mouse gastrocnemius muscle. SXT injection treatment increased capillary density and promoted angiogenesis in hindlimb ischemia. Moreover, SXT injection enhanced the expression of VEGF-A and PDGF-BB at both mRNA and protein levels in ischemic tissue of mice. SXT injection and its main active peptides dramatically increased the migration and capillary tube formation of HUVECs. SXT injection and its peptides enhanced protein expressions of the phosphorylation of MYPT1, Cofilin, and LIMK1. DSYVGDEAQSKR, YNELRVAPEEHP, and IQFLPEGSPVTM may act as the active components of SXT injection. CONCLUSION: SXT injection promoted angiogenesis and improved function recovery in hindlimb ischemia mice by regulation of VEGF-A/PDGF-BB. Moreover, SXT injection and its active peptides induced cell migration and tube formation in HUVECs through activating the MYPT1/LIMK1/Cofilin pathway. This study provided experimental basis for SXT injection in the treatment of ischemic diseases and revealed the effective substance of SXT injection in regulating angiogenesis, providing better evidence for the clinical application of SXT injection.

Acute effects of ambient nitrogen oxides and interactions with temperature on cardiovascular mortality in Shenzhen, China.

BACKGROUND: Though inconsistent, acute effects of ambient nitrogen oxides on cardiovascular mortality have been reported. Whereas, interactive roles of temperature on their relationships and joint effects of different indicators of nitrogen oxides were less studied. This study aimed to extrapolate the independent roles of ambient nitrogen oxides and temperature interactions on cardiovascular mortality. METHODS: Data on mortality, air pollutants, and meteorological factors in Shenzhen from 2013 to 2019 were collected. Three indicators including nitric oxide (NO), nitrogen dioxide (NO2), and nitrogen oxides (NOX) were studied. Adjusted generalized additive models (GAMs) were applied to analyse their associations with cardiovascular mortality in different groups. RESULTS: The average daily concentrations of NO, NO2, and NOX were 11.7 µg/m3, 30.7 µg/m3, and 53.2 µg/m3, respectively. Significant associations were shown with each indicator. Cumulative effects of nitrogen oxides were more obvious than distributed lag effects. Males, population under 65 years old, and population with stroke-related condition were more susceptible to nitrogen oxides. Adverse effects of nitrogen oxides were more significant at low temperature. Impacts of NO2 on cardiovascular mortality, and NO on stroke mortality were the most robust in the multi-pollutant models, whereas variations were shown in the other relationships. CONCLUSIONS: Low levels of nitrogen oxides showed acute and adverse impacts and the interactive roles of temperature on cardiovascular mortality. Cumulative effects were most significant and joint effects of nitrogen oxides required more attention. Population under 65 years old and population with stroke-related health condition were susceptible, especially days at lower temperature.

An atomic perspective on improving daptomycin's activity.

BACKGROUND: Recently, through comprehensive medicinal chemistry efforts, we have found a new daptomycin analogue, termed kynomycin, showing enhanced activity against both methicillin-resistant S. aureus and vancomycin-resistant Enterococcus in vitro and in vivo, with improved pharmacokinetics and lower cytotoxicity than daptomycin. METHODS: In this study we compared the physicochemical properties of kynomycin with those of daptomycin from an atomic perspective by using Nuclear Magnetic Resonance spectroscopy and Molecular Dynamics simulations. RESULTS AND CONCLUSION: We observed that kynurenine methylation changes daptomycin's key physicochemical properties; its calcium dependent oligomerization efficiency is improved and the modified kynurenine strengths contacts with the lipid tail and tryptophan residues. In addition, it is observed that, compared to daptomycin, kynomycin tetramer is more stable and binds stronger to calcium. The combined experiments provide key clues for the improved antibacterial activity of kynomycin. GENERAL SIGNIFICANCE: We expect that this approach will help study the calcium binding and oligomerization features of new calcium dependent peptide antibiotics.

Improving influenza surveillance based on multi-granularity deep spatiotemporal neural network.

Influenza is a common respiratory disease that can cause human illness and death. Timely and accurate prediction of disease risk is of great importance for public health management and prevention. The influenza data belong to typical spatiotemporal data in that influenza transmission is influenced by regional and temporal interactions. Many existing methods only use the historical time series information for prediction, which ignores the effect of spatial correlations of neighboring regions and temporal correlations of different time periods. Mining spatiotemporal information for risk prediction is a significant and challenging issue. In this paper, we propose a new end-to-end spatiotemporal deep neural network structure for influenza risk prediction. The proposed model mainly consists of two parts. The first stage is the spatiotemporal feature extraction stage where two-stream convolutional and recurrent neural networks are constructed to extract the different regions and time granularity information. Then, a dynamically parametric-based fusion method is adopted to integrate the two-stream features and making predictions. In our work, we demonstrate that our method, tested on two influenza-like illness (ILI) datasets (US-HHS and SZ-HIC), achieved the best performance across all evaluation metrics. The results imply that our method has outstanding performance for spatiotemporal feature extraction and enables accurate predictions compared to other well-known influenza forecasting models.

Insight into the practical performance of RT-PCR testing for SARS-CoV-2 using serological data: a cohort study.

BACKGROUND: Virological detection of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) through RT-PCR has limitations for surveillance. Serological tests can be an important complementary approach. We aimed to assess the practical performance of RT-PCR-based surveillance protocols and determine the extent of undetected SARS-CoV-2 infection in Shenzhen, China. METHODS: We did a cohort study in Shenzhen, China and attempted to recruit by telephone all RT-PCR-negative close contacts (defined as those who lived in the same residence as, or shared a meal, travelled, or socially interacted with, an index case within 2 days before symptom onset) of all RT-PCR-confirmed cases of SARS-CoV-2 detected since January, 2020, via contact tracing. We measured anti-SARS-CoV-2 antibodies in serum samples from RT-PCR-negative close contacts 2-15 weeks after initial virological testing by RT-PCR, using total antibody, IgG, and IgM ELISAs. In addition, we did a serosurvey of volunteers from neighbourhoods with no reported cases, and from neighbourhoods with reported cases. We assessed rates of infection undetected by RT-PCR, performance of RT-PCR over the course of infection, and characteristics of individuals who were seropositive on total antibody ELISA but RT-PCR negative. FINDINGS: Between April 12 and May 4, 2020, we enrolled and collected serological samples from 2345 (53·0%) of 4422 RT-PCR-negative close contacts of cases of RT-PCR-confirmed SARS-CoV-2. 1175 (50·1%) of 2345 were close contacts of cases diagnosed in Shenzhen with contact tracing details, and of these, 880 (74·9%) had serum samples collected more than 2 weeks after exposure to an index case and were included in our analysis. 40 (4·5%) of 880 RT-PCR-negative close contacts were positive on total antibody ELISA. The seropositivity rate with total antibody ELISA among RT-PCR-negative close contacts, adjusted for assay performance, was 4·1% (95% CI 2·9-5·7), which was significantly higher than among individuals residing in neighbourhoods with no reported cases (0·0% [95% CI 0·0-1·1]). RT-PCR-positive individuals were 8·0 times (95% CI 5·3-12·7) more likely to report symptoms than those who were RT-PCR-negative but seropositive, but both groups had a similar distribution of sex, age, contact frequency, and mode of contact. RT-PCR did not detect 48 (36% [95% CI 28-44]) of 134 infected close contacts, and false-negative rates appeared to be associated with stage of infection. INTERPRETATION: Even rigorous RT-PCR testing protocols might miss a substantial proportion of SARS-CoV-2 infections, perhaps in part due to difficulties in determining the timing of testing in asymptomatic individuals for optimal sensitivity. RT-PCR-based surveillance and control protocols that include rapid contact tracing, universal RT-PCR testing, and mandatory 2-week quarantine were, nevertheless, able to contain community spread in Shenzhen, China. FUNDING: The Bill & Melinda Gates Foundation, Special Foundation of Science and Technology Innovation Strategy of Guangdong Province, and Key Project of Shenzhen Science and Technology Innovation Commission.

A Short-Term Prediction Model at the Early Stage of the COVID-19 Pandemic Based on Multisource Urban Data.

The ongoing coronavirus disease 2019 (COVID-19) pandemic spread throughout China and worldwide since it was reported in Wuhan city, China in December 2019. 4 589 526 confirmed cases have been caused by the pandemic of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), by May 18, 2020. At the early stage of the pandemic, the large-scale mobility of humans accelerated the spread of the pandemic. Rapidly and accurately tracking the population inflow from Wuhan and other cities in Hubei province is especially critical to assess the potential for sustained pandemic transmission in new areas. In this study, we first analyze the impact of related multisource urban data (such as local temperature, relative humidity, air quality, and inflow rate from Hubei province) on daily new confirmed cases at the early stage of the local pandemic transmission. The results show that the early trend of COVID-19 can be explained well by human mobility from Hubei province around the Chinese Lunar New Year. Different from the commonly-used pandemic models based on transmission dynamics, we propose a simple but effective short-term prediction model for COVID-19 cases, considering the human mobility from Hubei province to the target cities. The performance of our proposed model is validated by several major cities in Guangdong province. For cities like Shenzhen and Guangzhou with frequent population flow per day, the values of [Formula: see text] of daily prediction achieve 0.988 and 0.985. The proposed model has provided a reference for decision support of pandemic prevention and control in Shenzhen.