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Background: In recent years, deep learning has been widely used in a variety of ophthalmic diseases. As a common ophthalmic disease, meibomian gland dysfunction (MGD) has a unique phenotype in in-vivo laser confocal microscope imaging (VLCMI). The purpose of our study was to investigate a deep learning algorithm to differentiate and classify obstructive MGD (OMGD), atrophic MGD (AMGD) and normal groups.Methods: In this study, a multi-layer deep convolution neural network (CNN) was trained using VLCMI from OMGD, AMGD and healthy subjects as verified by medical experts. The automatic differential diagnosis of OMGD, AMGD and healthy people was tested by comparing its image-based identification of each group with the medical expert diagnosis. The CNN was trained and validated with 4,985 and 1,663 VLCMI images, respectively. By using established enhancement techniques, 1,663 untrained VLCMI images were tested.Results: In this study, we included 2,766 healthy control VLCMIs, 2,744 from OMGD and 2,801 from AMGD. Of the three models, differential diagnostic accuracy of the DenseNet169 CNN was highest at over 97%. The sensitivity and specificity of the DenseNet169 model for OMGD were 88.8 and 95.4%, respectively; and for AMGD 89.4 and 98.4%, respectively.Conclusion: This study described a deep learning algorithm to automatically check and classify VLCMI images of MGD. By optimizing the algorithm, the classifier model displayed excellent accuracy. With further development, this model may become an effective tool for the differential diagnosis of MGD.

Background and aims Protein phosphatase 2A (PP2A) is associated with many cancers. This study aimed to clarify whether PPP2CA, which encodes the alpha isoform of the catalytic subunit of PP2A, plays a role in hepatocellular carcinoma (HCC) and to identify the potential underlying molecular pathways. Methods Based on bioinformatics, public databases and our in-house RNA-Seq database, we analyzed the clinical value and molecular mechanism of PPP2CA in HCC. Results Data were analyzed from 2,545 patients with HCC and 1,993 controls without HCC indexed in The Cancer Genome Atlas database, the Gene Expression Omnibus database and our in-house RNA-Seq database. PPP2CA expression was significantly higher in HCC tissue than in non-cancerous tissues (standardized mean difference: 0.69, 95% confidence interval [CI]: 0.50-0.89). PPP2CA expression was able to differentiate HCC from non-HCC, with an area under the summary receiver operator characteristic curve of 0.79 (95% CI: 0.75-0.83). Immunohistochemistry of tissue sections confirmed that PPP2CA protein was up-regulated in HCC tissues. High PPP2CA expression in HCC patients was associated with shorter overall, progression-free and disease-free survival. Potential molecular pathways through which PPP2CA may be involved in HCC were determined using miRWalk 2.0 as well as analysis of Gene Ontology categories, Kyoto Encyclopedia of Genes and Genomes pathways, and protein-protein interaction networks. Conclusions PPP2CA is up-regulated in HCC and higher expression correlates with worse prognosis. PPP2CA shows potential as a diagnostic marker for HCC. Future studies should examine whether PPP2CA contributes to HCC through the candidate microRNAs, pathways and hub genes identified in this study.

Synchronised harmonic analysis that utilises GPS signals to synchronise harmonic measurements enables advanced power quality analysis in smart grid. However, it is difficult to put this promising technology into practice due to an extremely high requirement on data storage and processing. To overcome this problem, this study presents a novel Hadoop-based framework for big data analysis of synchronised harmonics in distribution networks. The proposed framework facilitates harmonic data processing associated with data storage and advanced analysis based on big data techniques. Under this framework, a big matrix multiplication algorithm based on MapReduce programming model solving the harmonic state estimation problem is deployed in the stage of data processing. A MapReduce-based harmonics distortion calculation is implemented as an advanced analysis for harmonics. Comprehensive numerical studies are carried out to analyse the characteristics of the proposed algorithm and verify the effectiveness of the proposed framework.

Laribacter hongkongensis is a potential emerging pathogen, associated with community-acquired diarrhoea. For epidemiological purposes, different molecular typing methods, such as pulsed-field gel electrophoresis (PFGE) and multi-locus sequence typing, have been developed for this pathogen. However, these methods require specialized equipment and costly reagents. More importantly, they are labour-intensive and time-consuming, which is not really suitable for foodborne disease outbreak investigations. In this study, we developed a rapid and reliable method using 22-mer primers specific for the enterobacterial repetitive intergenic consensus sequence (ERIC). PFGE was used for comparison, to evaluate this method. A total of 81 isolates of L. hongkongensis were examined: 79 isolates recovered from food of diverse origins and two strains derived from patients with L. hongkongensis-associated infection. Typing patterns and clustering analysis indicated that the 81 L. hongkongensis isolates were grouped into 21 and 13 genotypes by ERIC-PCR and PFGE, respectively. ERIC-PCR was found as reproducible as PFGE. A high percentage (70.4 %) of isolates yielded distinguishable ERIC-PCR patterns, which were concordant with the results from PFGE. These results suggest that ERIC-PCR is valuable for use in the epidemiological investigation of L. hongkongensis.

Laribacter hongkongensis is a novel emerging pathogen associated with human gastroenteritis. We aimed to investigate the prevalence, antimicrobial resistance and genotypic relationship of 199 L. hongkongensis isolates from 690 intestinal samples of fish and frogs. These samples were collected from retail markets in the city of Guangzhou in southern China from October 2008 to September 2009. L. hongkongensis was detected in from 80 (16.3%) out of 490 freshwater fish, and this number included 76 (32.3%) out of 235 grass carp and 4 (14.8%) out of 27 bighead carp. A higher isolation rate of 59.5% (119 out of 200) was observed in edible frogs. The isolation rate was highest in the spring in comparison with other seasons. Notably, 63.8% of the isolates were resistant to at least one class of antimicrobial agents. Analysis by pulsed-field gel electrophoresis (PFGE) revealed that the isolates could be grouped into three clusters. Isolates from fish intestines were grouped into two clusters: cluster I and II. Isolates of frog-origin and several fish-origin isolates were grouped into cluster III. Two patient-derived strains could be classed into cluster III. Extensive genetic heterogeneity among the isolates was observed. The results indicate that L. hongkongensis isolates exhibits host tropism, extensive resistance to widely used antimicrobials and diverse biological evolution in an aquatic environment. The frog is more likely than the freshwater fish to be the potential source for human infection with L. hongkongensis.

An epidemic of severe acute respiratory syndrome (SARS) began in Foshan municipality, Guangdong Province, China, in November 2002. We studied SARS case reports through April 30, 2003, including data from case investigations and a case series analysis of index cases. A total of 1,454 clinically confirmed cases (and 55 deaths) occurred; the epidemic peak was in the first week of February 2003. Healthcare workers accounted for 24% of cases. Clinical signs and symptoms differed between children (18 years) and older persons (or =65 years). Several observations support the hypothesis of a wild animal origin for SARS. Cases apparently occurred independently in at least five different municipalities; early case-patients were more likely than later patients to report living near a produce market (odds ratio undefined; lower 95% confidence interval 2.39) but not near a farm; and 9 (39%) of 23 early patients, including 6 who lived or worked in Foshan, were food handlers with probable animal contact.

Sixty-one SARS coronavirus genomic sequences derived from the early, middle, and late phases of the severe acute respiratory syndrome (SARS) epidemic were analyzed together with two viral sequences from palm civets. Genotypes characteristic of each phase were discovered, and the earliest genotypes were similar to the animal SARS-like coronaviruses. Major deletions were observed in the Orf8 region of the genome, both at the start and the end of the epidemic. The neutral mutation rate of the viral genome was constant but the amino acid substitution rate of the coding sequences slowed during the course of the epidemic. The spike protein showed the strongest initial responses to positive selection pressures, followed by subsequent purifying selection and eventual stabilization.

The highly pathogenic avian influenza A (HPAI) viruses of the H5N1 subtype infect poultry and have also been spreading to humans. Although new antiviral drugs and vaccinations can be effective, rapid detection would be more efficient to control the outbreak of infections. In this study, a phage-display library was applied to select antibody fragments for HPAI strain A/Hubei/1/2010. As a result, three clones were selected and sequenced. A hemagglutinin inhibition assay of the three scFvs revealed that none exhibited hemagglutination inhibition activity towards the H5N1 virus, yet they showed a higher binding affinity for several HPAI H5N1 strains compared with other influenza viruses. An ELISA confirmed that the HA protein was the target of the scFvs, and the results of a protein structure simulation showed that all the selected scFvs bound to the HA2 subunit of the HA protein. In conclusion, the three selected scFVs could be useful for developing a specific detection tool for the surveillance of HPAI epidemic strains.

To analyze the current situation on China Infectious Disease Automated-alert and Response System (CIDARS) in Guangdong province, China.Early-warning signals and response time were analyzed by using three approaches of CIDARS. Positive rates of early-warning signals and error early-warning rates prior and after the adjustment,were compared.Totally, 114 585 early-warning signals appeared, with an average response time of 1.35 hours from April 21, 2008 to December 31, 2012. There were 12,394 early-warning signals in terms of fixed threshold method with a positive rate of 7.96%. 85 727 early-warning signals appeared under the mobile percentile method with a positive rate of 0.85%. There were 16,464 early-warning signals by using accumulation and control chart methods,with a positive rate of 1.82%. Results showed there was a positive correlation between the number of reported cases and the number of early-warning signals (r = 0.924, P0.01). The overall positive rate in Guangdong province increased from 1.48% to 2.14%, after the adjustment done by the Chinese Center for Disease Control and Prevention in 2010. The error early-warning rates regarding eight infectious diseases including hepatitis A, bacillary or amebic dysentery, both typhoid and paratyphoid fevers had reduced.The early-warning signal response appeared timely in CIDARS with good operation. However, despite the improvement on the efficacy of CIDARS, some functions and parameters of the systems still need to be adjusted.

To analyze the epidemiological and etiological characteristics of diarrheal disease among children under 5 years of age in Guangdong province, in 2012.64 hospitals in 21 cities were chosen as the diarrheal syndromic surveillance sites, of which 14 hospitals were selected to carry out etiological surveillance among children under 5 years of age, including isolation and culture of both Vibrio cholera and Shigella as well as nucleic acid detection of rotavirus and norovirus by PCR. Descriptive method was used to analyze data from syndromic and etiological surveillance programs on diarrheal, from 1932 parents of the children.In 2012, the outpatient attendance rate on diarrheal among children under 5 years was 0.8%. The proportion of diarrheal in children under 5-year-olds was 63.5%, among the total number of diarrheal outpatients at the outpatient clinics under surveillance program. The morbidity of infectious diarrhea was 1454.5/10 million in children under 5 years of age. A total number of 1932 specimens were collected from children under 5 years of age, in the outpatient department. Among these specimens,Vibrio cholera appeared all negative but one was Shigella positive and proved to be Sh. sonnei. The positive rates of rotavirus and norovirus were 14.1% (273/1932)and 16.9% (326/1932). Both rotavirus and norovirus were found in 24 specimens, with a positive rate as 1.2% . 112 specimens were successfully gene sequenced for rotavirus, of which 33.9% as G1[P8] genotype, 25.9% as G9[P8], 12.5% as G2[P4] and 9.8% as G3[P8] respectively. 90 specimens were successfully gene-sequenced for norovirus, of which 76.7% as G II.4 genotype. Genetic subtypes of G II. 4/2006b, accounted for 50.0% and could be detected around the year except for June and December. New G II. 4/Sydney Strain_2012 was first detected in August and became the predominant in December. In addition, 5 specimens belonged to G I genotype with other 16 subtypes of G II.Results from our study proved that children under 5 years of age belonged to high-risk group for diarrheal disease in Guangdong province. Rotavirus and norovirus were both diverse in terms of genome.

To understand the pathogen-carrying status of hand-foot-mouth disease (HFMD) among healthy people in Guangdong province.Stool specimens were collected randomly on 7 age groups from 7 cities in Guangdong province. Real-time RT-PCR was used to detect enterovirus (EV), enterovirus 71 (EV71) and coxsackie virus A16 (CA16).Altogether, 1285 stool specimens were collected. The positive rates of EV71, CA16 and other enterovirus were 0.39% (5/1285), 0.23% (3/1285) and 7.00% (90/1285), respectively. The highest EV71 positive rate (1.79%) was among the 4-6-year-old group, followed by the age group 0 - 3 with positive rate as 0.67%. EV71 was not found among the rest age groups. The highest CA16 positive rate (1.35%) was among the 4 - 6 year-olds group, but the CA16 was not found among the rest age groups. EV71 was only found among native population, with the positive-rate as 0.47%. CA16-positive rate was 0.19% among the native population and 0.85% among floating population, with no significant difference found (P0.05). The EV71 positive rate was 0.36% among rural residents and 0.54% among urban residents, but with no significant difference (P0.05). All CA16 was found among the urban residents.Recessive infection of EV71 and CA16 were only found among 0-6 year-old group but not found among other groups, which suggested that the approaches on prevention and control should be targeted to all children especially on pre-school children.

Angiostrongyliasis has been frequently reported from the People's Republic of China during the last decade. An outbreak of angiostrongyliasis among migrant laborers in Guangning, Guangdong Province is described here. A questionnaire was developed to collect epidemiological and clinical information about 17 migrant laborers from the Bai ethnic group in Dali, Yunnan Province. Serum samples were collected and tested by enzyme-linked immunosorbent assay. Rats and mollusks from the same area where patients had collected Pomacea canaliculata were examined for presence of Angiostrongylus cantonensis. All 17 Bai migrant laborers consumed P. canaliculata and six had meningitis 3-19 days after consumption of P. canaliculata. Headache, myalgia and fatigue were the most common symptoms. Blood samples from 5 patients were positive for antibodies to A. cantonensis. The places where the migrant laborers collected P. canaliculata were identified as endemic areas for A. cantonensis. This outbreak highlights the vulnerability of migrants to angiostrongyliasis.

To understand the infection status of pandemic 2009 H1N1 influenza after the first epidemic wave and to estimate the infected population.Multi-stage stratified random sampling was introduced with 4500 subjects chosen in Guangdong province. 1500 people were selected from 5 districts (3 streets were selected in every district) in Guangzhou city which was representing the large cities. 1500 people were respectively selected from medium-sized city and rural areas, including 20 cities (1 county or district was selected in every city, at least 1 street or town was selected in every county or district respectively and then 1 - 2 residential area or county was selected in every street or township, respectively). Every sample was selected in accordance with the principle of random sampling, excluding those who had injected with novel H1N1 vaccine. We used hemagglutination inhibition test to understand the serum antibody level of novel H1N1, with title of 1:40 as positive.A number of 4319 specimens, distributed in 21 cities, 25 counties, 85 streets or townships, 144 residential areas, were tested, with an overall positive rate as 22.82% (985/4319). The positive rate of those who had no symptoms of cold since June was 23.47% (471/2007). The positive rate of those who had fever, cough or sore throat was 26.25% (714/2720). The positive rate of those who had influenza-like illness (ILI) was 29.69% (337/1135).The infection rate in the first epidemic wave of the novel influenza A (H1N1) pandemic in Guangdong province was 22.82% (985/4317). Based on the number of residents in Guangdong province, the number of natural was estimated to have reached 21.78 million.

To analysis the risk factors influencing nosocomial infection of severe acute respiratory syndrome (SARS) in health-care workers and to evaluate effectiveness of its control and preventive measures in 13 key hospitals caring for SARS patients.Number of SARS patients, clinical conditions of them, its attack rate in health-care workers, and characteristics of hospitals, including their environment, isolating measures, etc. were investigated at the 13 hospital in Guangzhou to analyze the risk factors influencing nosocomial infection of SARS and its attack rates in health-care workers before and after implementation of preventive measures and to evaluate their effectiveness.Totally, 841 patients with SARS were treated at the 13 hospitals in Guangzhou and 285 health-care workers caring for them infected nosocomially. Attack rate in health-care workers was higher at general hospitals, hospital accepting more cases in critical conditions and hospitals with poor precautious measures, and lower in hospitals with isolated wards or areas, or department of infection, specially caring for SARS patients, and those with effective intervention measures to prevent secondary infection.Nosocomial infection of SARS in health-care workers was affected by clinical condition of SARS patients, characteristics and environment of hospitals and their personal protective measures adopted.

To evaluate the effectiveness of personal protective measures of health care workers (HCWs) against severe acute respiratory syndrome (SARS).A case-control study from ten hospitals in Guangdong, with 180 non-infected and 77 infected staff members that accessed the isolation unit every day, and participated in direct first aid for severe SARS patients. All participants were surveyed about how they were using personal protective equipment (PPE), protective drugs and hygiene habits when caring for patients with SARS. Statistical analysis was done with either chi(2) or Fisher's exact test for univariate analysis, whereas we used forward stepwise selection (Waldesian) for logistic regression.Univariate analysis showed that mask, gown, gloves, goggles, footwear, "hand-washing and disinfecting", gargle, "membrane protection", "taking shower and changing clothing after work", "avoid from eating and drinking in ward", oseltamivir phospha tall had protective effects (P0.05), but stepwise logistic regression showed significant differences for mask (OR = 0.78, 95% CI: 0.60 - 0.99), goggles (OR = 0.20, 95% CI: 0.10 - 0.41) and footwear (OR = 0.58, 95% CI: 0.39 - 0.86). Analysis for linear trend in proportions showed that dose response relationship existed in mask, gown, gloves, goggles, footwear, gargle, "membrane protection" and "taking shower and changing dree after work" (P0.01). The attack rate of HCWs who were rescuing severe SARS patients without any PPE was 61.5% (16/26). It seemed that the more the protective measures were used, the higher the protective effect was (P0.001), and could reach 100% if mask, gown, gloves, goggles, footwear, "hand-washing and disinfecting" were all used at the same time.Nosocomial infection of SARS can be prevented effectively by precautions against droplets and personal contact. HCWs must take strict protection according to the guidance of WHO or Chinese MOH and pay attention to personal hygiene.

To explore epidemiological features and risk factors of severe acute respiratory syndrome (SARS) in Guangdong Province of China, so as to work out effective strategies for its better control.A total of 1 511 clinically confirmed SARS cases in Guangdong Province of China from November 16, 2002 to Jun 15, 2003 were retrospectively analyzed.The first SARS case was identified in Foshan municipality on November 16, 2002, followed by 1 511 clinically confirmed cases (including 58 deaths) up to May 15, 2003. Of all cases, health care workers and community family cluster cases accounted for 19.38% and 12.04%. 65.86% SARS patients aged 20 - 49 years, and increased incidence was positively related to their ages. 95.97% cases lived in the following five cities around Pearl Delta Area: Foshan, Guangzhou, Shenzhen, Zhongshan, and Jiangmen. Eleven early reported cases in the communities took animal-related positions. Face-to-face contacts with infected droplets were the main transmission route. An epidemic peak occurred during January 28 to February 26, and those cases accounted for 50.69% of total. Incidence, mortality, and case fatality of SARS were 1.77/100,000, 0.07/100,000, and 3.84% respectively. The mean incubation period was 4.5 days.The most effective way to control SARS is to break the chain of transmission from infected to healthy persons-early identification, prompt and effective isolation, and vigorous close contact tracing. Hospital infections among health care workers is critical. Several observations support the hypothesis of an animal origin for the disease.

To understand the epidemiological characteristics of severe acute respiratory syndrome (SARS) outbreaks in some areas of Guangdong province and to provide scientific basis for prevention and control measures against it.Standardized questionnaire was used on individual cases. Data on the epidemiological characteristics as time, place, persons and aggregation status of SARS cases, development of the epidemics, were analyzed with software EPI 6.0.The incidence of SARS in Guangdong province was 1.72/100,000 with case fatality rate as 3.64%. Most cases of SARS occurred between the last ten days of January and the first ten days of February with the peak (61.88% of the patients) occurred in the first ten days of February. As to the distribution of place, Pearl river delta region-economically developed with great number of mobile population-was heavily affected areas (account for 96.66% of the total patients). The majority of patients were young adults and medical staff seemed to be the most affected subgroup (account for 24.9% of the patients in total). Family and hospital aggregation of patients comprised the another two important characteristics of SARS (account for 37.1% of the total patients).Current knowledge on SARS suggested that it was an air-borne infectious disease with human beings served as the source of infection. The incubation period of the disease was from 1 to 12 days with a median of 4 days. Respiratory secretions and close contact contributed to person-to-person transmission. Most cases were distributed in Pearl river delta region, an area famous for its economic development and heavy flow of mobile population.

BackgroundThe second wave of avian influenza H7N9 virus outbreak in humans spread to the Guangdong province of China by August of 2013 and this virus is now endemic in poultry in this region.MethodsFive patients with H7N9 virus infection admitted to our hospital during August 2013 to February 2014 were intensively investigated. Viral load in the respiratory tract was determined by quantitative polymerase chain reaction (Q-PCR) and cytokine levels were measured by bead-based flow cytometery.ResultsFour patients survived and one died. Viral load in different clinical specimens was correlated with cytokine levels in plasma and broncho-alveolar fluid (BALF), therapeutic modalities used and clinical outcome. Intravenous zanamivir appeared to be better than peramivir as salvage therapy in patients who failed to respond to oseltamivir. Higher and more prolonged viral load was found in the sputum or endotracheal aspirates compared to throat swabs. Upregulation of proinflammatory cytokines IP-10, MCP-1, MIG, MIP-1α/β, IL-1β and IL-8 was found in the plasma and BALF samples. The levels of cytokines in the plasma and viral load were correlated with disease severity. Reactivation of herpes simplex virus type 1(HSV-1) was found in three out of five patients (60%).ConclusionExpectorated sputum or endotracheal aspirate specimens are preferable to throat swabs for detecting and monitoring H7N9 virus. Severity of the disease was correlated to the viral load in the respiratory tract as well as the extents of cytokinemia. Reactivation of HSV-1 may contribute to clinical outcome.