The Global Infectious Diseases Epidemic Information Monitoring System: Development and Usability Study of an Effective Tool for Travel Health Management in China.

BACKGROUND: Obtaining comprehensive epidemic information for specific global infectious diseases is crucial to travel health. However, different infectious disease information websites may have different purposes, which may lead to misunderstanding by travelers and travel health staff when making accurate epidemic control and management decisions. OBJECTIVE: The objective of this study was to develop a Global Infectious Diseases Epidemic Information Monitoring System (GIDEIMS) in order to provide comprehensive and timely global epidemic information. METHODS: Distributed web crawler and cloud agent acceleration technologies were used to automatically collect epidemic information about more than 200 infectious diseases from 26 established epidemic websites and Baidu News. Natural language processing and in-depth learning technologies have been utilized to intelligently process epidemic information collected in 28 languages. Currently, the GIDEIMS presents world epidemic information using a geographical map, including date, disease name, reported cases in different countries, and the epidemic situation in China. In order to make a practical assessment of the GIDEIMS, we compared infectious disease data collected from the GIDEIMS and other websites on July 16, 2019. RESULTS: Compared with the Global Incident Map and Outbreak News Today, the GIDEIMS provided more comprehensive information on human infectious diseases. The GIDEIMS is currently used in the Health Quarantine Department of Shenzhen Customs District (Shenzhen, China) and was recommended to the Health Quarantine Administrative Department of the General Administration of Customs (China) and travel health-related departments. CONCLUSIONS: The GIDEIMS is one of the most intelligent tools that contributes to safeguarding the health of travelers, controlling infectious disease epidemics, and effectively managing public health in China.

Active Enhancer Assessment by H3K27ac ChIP-seq Reveals Claudin-1 as a Biomarker for Radiation Resistance in Colorectal Cancer.

BACKGROUND: Colorectal cancer (CRC) represents the third most common malignant tumor in the worldwide. Radiotherapy is the common therapeutic treatment for CRC, but radiation resistance is often encountered. ChIP-seq of Histone H3K27 acetylation (H3K27ac) has revealed enhancers that play an important role in CRC. This study examined the relationship between an active CRC enhancer and claudin-1 (CLDN1), and its effect on CRC radiation resistance. METHODS: The target CRC genes of active enhancers were obtained from public H3K27ac ChIP-seq, and the genes highly expressed in radio-resistant CRC were screened and intersected with enhancer-driven genes. The clinical roles of CLDN1 in radiation resistance were examined using the t-test, standard mean deviation (SMD), summary receiver operating characteristic curve and Kaplan-Meier curves. The co-expressed genes of CLDN1 were calculated using Pearson Correlation analysis, and Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes and Gene Set Variation Analysis (GSVA) analyses were used to examine the molecular mechanisms of CLDN1. RESULTS: Total 13 703 CRC genes were regulated by enhancers using 58 H3K27ac ChIP-seq. Claudin-1 (CLDN1) was enhancer-driven and notably up-regulated in CRC tissues compared to non-CRC controls, with a SMD of 3.45 (95 CI % = .56-4.35). CLDN1 expression was increased in radiation-resistant CRC with a SMD of .42 (95% CI = .16-.68) and an area under the curve of .74 (95% CI = .70-.77). The cell cycle and immune macrophage levels were the most significant pathways associated with CLDN1. CONCLUSION: CLDN1 as an enhancer-regulated gene that can boost radiation resistance in patients with CRC.

Assessment of the Predictive Role of Serum Lipid Profiles in Breast Cancer Patients Receiving Neoadjuvant Chemotherapy.

PURPOSE: Effective predictors of the response to neoadjuvant chemotherapy (NAC) are still insufficient. This study aimed to investigate the predictive value of serum lipid profiles for the response to NAC in breast cancer patients. METHODS: A total of 533 breast cancer patients who had received NAC were retrospectively studied. The pretreatment of serum lipids, including total cholesterol (TC), triglycerides (TG), high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), and lipoprotein-α, and clinicopathological characteristics were collected to assess their predictive roles. RESULTS: Breast cancer patients had significantly lower TC, TG, HDL-C, and LDL-C levels than normal individuals. Among these indicators, TG and LDL-C levels and HDL-C level increased and decreased significantly after NAC, respectively. In estrogen receptor (ER)-positive patients, increased LDL-C level was associated with better outcomes. Moreover, the receiver operating characteristic curve analyses suggested that TG and HDL-C levels at diagnosis can be used as predictors of the response to NAC only in the ER-positive subgroup. According to univariate analyses, patients with low TG level (< 1.155 mmol/L) or high HDL-C level (≥ 1.305 mmol/L) in the ER-positive subgroup had more favorable clinical responses than the other patients in the subgroup. Furthermore, according to multivariate analyses, a high HDL-C level (≥ 1.305 mmol/L, p = 0.007) was an independent predictor of NAC efficacy. CONCLUSION: High HDL-C level (≥ 1.305 mmol/L) before NAC and increased LDL-C level after NAC were associated with the better treatment response in ER-positive breast cancer patients. These results are potentially considered beneficial in establishing treatment decisions.

Scenario-based simulation of land use in Yingtan (Jiangxi Province, China) using an integrated genetic algorithm-cellular automata-Markov model.

Yingtan is a rapidly urbanizing city in Jiangxi Province, South China. During rapid urbanization, construction land is expanded at the expense of cropland and forest. Although economic benefits are gained, ecological and environmental damage is irreversible. In this study, a methodological framework for land use simulation using an integrated genetic algorithm-cellular automata-Markov model is proposed to assess the relationship between economic development and cropland protection in Yingtan. This framework considers both the economic and ecological benefits of different land use types. Three land use scenarios are evaluated to seek recommendations for land use practice. The results show that the areas with high suitability for cropland and construction are mainly concentrated in urban fringes. Under the green development scenario, the area of new construction land can meet the land demand for population growth and economic development proposed for 2025 based on population forecasting and government interviews. The expansion for construction land is decreased by ~ 35 km2 while the cropland area is increased by ~ 20 km2 compared with those under natural and controlled development scenarios. Additionally, ecological losses are lowest under the green development scenario. In conclusion, the green development scenario is conducive to both cropland and ecological protection, which is of relevance for future spatial planning in Yingtan.

Atom-Economic Silver-Catalyzed Difunctionalization of the Isocyano Group with Cyclic Oximes: Towards Pyrimidinediones.

An unprecedented silver-catalyzed difunctionalization of the isocyano group with cyclic oximes is described. This method allows efficient and atom-economic assembly of a vast array of structurally novel and interesting pyrimidinediones, and tolerates a range of functionalities. The resulting products can be easily converted into some useful compounds. Furthermore, the method can also be applied for the late-stage modification of a few biologically active molecules.

Assessment of thermotactile and vibrotactile thresholds for detecting sensorineural components of the hand-arm vibration syndrome (HAVS).

BACKGROUND: Thermotactile thresholds and vibrotactile thresholds are measured to assist the diagnosis of the sensorineural component of the hand-arm vibration syndrome (HAVS). OBJECTIVES: This study investigates whether thermotactile and vibrotactile thresholds distinguish between fingers with and without numbness and tingling. METHODS: In 60 males reporting symptoms of the hand-arm vibration syndrome, thermotactile thresholds for detecting hot and cold temperatures and vibrotactile thresholds at 31.5 and 125 Hz were measured on the index and little fingers of both hands. RESULTS: In fingers reported to suffer numbness or tingling, hot thresholds increased, cold thresholds decreased, and vibrotactile thresholds at both 31.5 and 125 Hz increased. With sensorineural symptoms on all three phalanges (i.e. numbness or tingling scores of 6), both thermotactile thresholds and both vibrotactile thresholds had sensitivities greater than 80% and specificities around 90%, with areas under the receiver operating characteristic curves around 0.9. There were correlations between all four thresholds, but cold thresholds had greater sensitivity and greater specificity on fingers with numbness or tingling on only the distal phalanx (i.e. numbness or tingling scores of 1) suggesting cold thresholds provide better indications of early sensorineural disorder. CONCLUSIONS: Thermotactile thresholds and vibrotactile thresholds can provide useful indications of sensorineural function in patients reporting symptoms of the sensorineural component of HAVS.

[Efficacy and safety of colistimethate sodium in critical patients: an in vitro study by using of Monte Carlo simulation].

OBJECTIVE: To evaluate the efficacy and safety of colistimethate sodium (CMS) for the treatment of critical patients infected by pan-drug resistant Acinetobacter baumannii (PDR-AB) or pan-drug resistant Pseudomonas aeruginosa (PDR-PA). METHODS: 321 isolates of PDR-AB and 204 isolates of PDR-PA from critical patients admitted to 35 intensive care units (ICUs) of grade two or above were collected from the Anhui Antimicrobial Resistance Investigation Net (AHARIN) program from September 2012 to September 2015, while the minimal inhibitory concentrations (MIC) of colistin were determined by the E-test. A series of Monte Carlo simulations was performed for CMS regimens (1 MU q8h, 2 MU q8h, and 3 MU q8h, and MU meant a million of unit), and the probability of achieving a 24-hour area under the drug concentration time curve (AUC24)/MIC ratio > 60 and risk of nephrotoxicity for each dosing regimen was calculated. Each simulation was run over three CLCr ranges: < 60, ≥ 60-90, ≥ 90-120 mL/min. The probability of target attainment (PTA) for the AUC24/MIC ratio was calculated using the partial MIC value, while the cumulative fraction of response (CFR) was determined by integrating each PTA with the MIC distributions, the value greater than or equal to 90% or more than 80% was set as the optimal dosing regimen or suboptimal dosing regimen respectively. The probability of average 24-hour serum concentrations up to 4 mg/L for three dosage regimens was used to predict the risks of nephrotoxicity. RESULTS: All 321 isolates of PDR-AB and 204 isolates of PDR-PA were susceptible to colistin, the MIC50/90 against PDR-AB were 0.5 mg/L and 1.0 mg/L, and those against PDR-PA were 0.5 mg/L and 1.5 mg/L, respectively. When recommended dose (1 MU q8h) was used for patients with CLCr of < 60 mL/min, high CFR value (89.78% for PDR-AB, 81.06% for PDR-PA) were obtained, but with a high risks of nephrotoxicity (> 32.51%). Moreover, low value of PTA (< 66.56%) was yielded for isolates with MIC of ≥ 1 mg/L. Recommended dose also yielded a low CFR value (56.97%-69.31% for PDR-AB, 44.76%-56.94% for PDR-PA) in patients with CLCr of ≥ 60-120 mL/min. When dose was increased to 2 MU q8h, CFR (77.45%-92.87%) and the risks of nephrotoxicity (< 0.15%) was optimal for patients with CLCr ≥ 60-120 mL/min, but low value of PTA (< 75.36%) was also yielded for isolates with MIC of ≥ 1 mg/L. The most aggressive dose of 3 MU q8h provided high CFR (> 89.24%) even in patients with CLCr ≥ 90-120 mL/min, and PTA was < 76.20% only for isolates with MIC of ≥ 1.5 mg/L, but this dosing scheme was associated with unacceptable risks of nephrotoxicity (> 33.68%). CONCLUSIONS: Measurement of MIC, individualized CMS therapy and therapeutic drug-level monitoring should be considered to achieve the optimal drug exposure and ensure the safety of CMS.

Assessment of two alternative standardised tests for the vascular component of the hand-arm vibration syndrome (HAVS).

BACKGROUND: Vibration-induced white finger (VWF) is the vascular component of the hand-arm vibration syndrome (HAVS). Two tests have been standardised so as to assist the diagnosis of VWF: the measurement of finger rewarming times and the measurement of finger systolic blood pressures (FSBPs). OBJECTIVES: This study investigates whether the two tests distinguish between fingers with and without symptoms of whiteness and compares individual results between the two test methods. METHODS: In 60 men reporting symptoms of the HAVS, the times for their fingers to rewarm by 4°C (after immersion in 15°C water for 5 min) and FSBPs at 30°C, 15°C and 10°C were measured on the same day. RESULTS: There were significant increases in finger rewarming times and significant reductions in FSBPs at both 15°C and 10°C in fingers reported to suffer blanching. The FSBPs had sensitivities and specificities >90%, whereas the finger rewarming test had a sensitivity of 77% and a specificity of 79%. Fingers having longer rewarming times had lower FSBPs at both temperatures. CONCLUSIONS: The findings suggest that, when the test conditions are controlled according to the relevant standard, finger rewarming times and FSBPs can provide useful information for the diagnosis of VWF, although FSBPs are more sensitive and more specific.

Ischemic heart disease deaths, disability-adjusted life years and risk factors in Fujian, China during 1990-2013: Data from the Global Burden of Disease Study 2013.

OBJECTIVES: Ischemic heart disease (IHD) is a large public health problem and is associated with a number of modifiable risk factors. The aim of this study was to estimate the IHD burden and attributable to risk factors in Fujian, China during 1990 to 2013. METHODS: IHD deaths, disability-adjusted life years (DALYs) and attributable to risk factors were estimated as part of the Global Burden of Disease (GBD) 2013 Study. Statistical models were employed to produce comprehensive results of IHD deaths, DALYs and attributable to risk. Means and 95% uncertainty intervals (UIs) were calculated for mortality and DALYs. The median of the percent change and 95% UI were determined for the period between 1990 and 2013. RESULTS: The age-standardized IHD deaths rate increased by 15.3% from 1990 [74.7 (95% UI 62.9-99.1) per 100,000] to 2013 [82.7 (56.5-95.5) per 100,000]. The age-standardized IHD DALYs has slightly decreased 8.8% from 1990 to 2013[from 1356.2 (1134.3-1732.1) to 1202.7 (879.6-1404.6) per 100,000]. All risks combined account for 94.7% (92.9%- 96.0%) of IHD DALYs for all ages in 2013. The five leading risk factors for all ages IHD DALYs were high systolic blood pressure, high total cholesterol, smoking, diet high in sodium, and high fasting plasma glucose. CONCLUSION: Despite decreased age-standardized IHD deaths and DALY rate since 1990, population growth and aging led to a higher global burden of IHD in 2013. Behavioral, environmental, and metabolic risks can explain most of the IHD DALYs providing many opportunities for prevention.

Assessment of the Access AMH assay as an automated, high-performance replacement for the AMH Generation II manual ELISA.

BACKGROUND: The manual Generation II (Gen II) ELISA method used to measure Anti-Müllerian Hormone (AMH) from Beckman Coulter has recently been superseded by a fully automated AMH immunoassay. The aim of this study was to evaluate the performance of the Access AMH assay and directly compare it to the modified Gen II ELISA method. A secondary aim was to verify that the fertile age-related AMH range previously established using the Gen II ELISA could be used to interpret results from the new automated Access assay. METHODS: The precision, stability, linearity, measurement range and detection limits were determined using recombinant AMH and patient serum samples. Different diluents and their effects on AMH concentration were compared. A correlation study was performed on patient samples to compare the Access AMH assay to the ELISA method on the Access2 and DxI800 analysers. The fertile AMH range was verified by comparing the 10th, 50th and 90th percentile values from both methods obtained from 489 natural conception pregnant women. RESULTS: The Access AMH assay showed good performance across the measuring range for both intra-assay (CV 1.41-3.30 %) and inter-assay (CV 3.04-5.76 %) precision and acceptable sample stability. Dilution of the high concentration samples with the recommended diluent resulted in a small but significant downward shift in values. The assay was linear over the range of values recommended by the manufacturer, allowing for accurate reporting within the reported range. The two assay types were highly correlated (R(2) = 0.9822 and 0.9832 for Access2 and DxI800, respectively), and the differences observed between the Access2 and DxI800 analysers were within clinically acceptable ranges, indicating that the methods are interchangeable. Furthermore, we demonstrated that results from the published reference range for the Gen II ELISA correlate with those from the automated Access AMH assay. CONCLUSION: Here, we verified the published performance of the Access AMH assay and showed excellent correlation with the Gen II ELISA method. Moreover, we validated this correlation by confirming that the results from a fertile AMH reference range established using the preceding Gen II ELISA are interchangeable with the new automated Access AMH assay.

Use of Monte Carlo simulation to evaluate the development of vancomycin resistance in meticillin-resistant Staphylococcus aureus.

Monte Carlo simulations were performed for various vancomycin dosage regimens to evaluate the potential for development of vancomycin resistance in meticillin-resistant Staphylococcus aureus (MRSA). When the target of free AUC(24)/MIC≥200 was considered (where AUC(24) is the area under the drug concentration-time curve in a 24-h interval and MIC is the minimum inhibitory concentration), a standard dose regimen (1000 mg every 12 h) yielded unacceptable simulated outcomes in patients with normal renal function; in particular, the probability of target attainment (PTA) was only 30.5% at an MIC of 1mg/L. For the same dosage regimens and the mutant prevention concentration (MPC)-based pharmacokinetic target (total AUC(24)/MPC>15), the cumulative fraction of response exceeded 80% for all renal function strata; low values of PTA (<80%) were obtained only for isolates with MPCs of ≥22.4 mg/L, which consisted of all 21 strains of heterogeneous vancomycin-intermediate S. aureus (hVISA) and a handful of non-hVISA strains with MICs of 2mg/L (32%; 16/50). Based on the current status of vancomycin resistance, we conclude that total AUC(24)/MPC>15, derived from in vivo experiments, is more suitable to predict the development of vancomycin resistance. In clinical practice, individualised vancomycin therapy should be considered to minimise selection of resistance mutations.

Tricuspid regurgitation and right ventricular function after mitral valve surgery with or without concomitant tricuspid valve procedure.

OBJECTIVES: To study the effect of mitral valve repair with or without concomitant tricuspid valve repair on functional tricuspid regurgitation and right ventricular function. METHODS: From 2001 to 2007, 1833 patients with degenerative mitral valve disease, a structurally normal tricuspid valve, and no coronary artery disease underwent mitral valve repair, and 67 underwent concomitant tricuspid valve repair. Right ventricular function (myocardial performance index and tricuspid annular plane systolic excursion) was measured before and after surgery using transthoracic echocardiography for randomly selected patients with tricuspid regurgitation grade 0, 1+, and 2+ (100 patients for each grade) and 93 with grade 3+/4+, 393 patients in total. RESULTS: In patients with mild (<3+) preoperative tricuspid regurgitation, mitral valve repair alone was associated with reduced tricuspid regurgitation and mild worsening of right ventricular function. Tricuspid regurgitation of 2+ or greater developed in fewer than 20%, and right ventricular function had improved, but not to preoperative levels, at 3 years. In patients with severe (3+/4+) preoperative tricuspid regurgitation, mitral valve repair alone reduced tricuspid regurgitation and improved right ventricular function; however, tricuspid regurgitation of 2+ or greater returned and right ventricular function worsened toward preoperative levels within 3 years. Concomitant tricuspid valve repair effectively eliminated severe tricuspid regurgitation and improved right ventricular function. Also, over time, tricuspid regurgitation did not return and right ventricular function continued to improve to levels comparable to that of patients with lower grades of preoperative tricuspid regurgitation. CONCLUSIONS: In patients with mitral valve disease and severe tricuspid regurgitation, mitral valve repair alone was associated with improved tricuspid regurgitation and right ventricular function. However, the improvements were incomplete and temporary. In contrast, concomitant tricuspid valve repair effectively and durably eliminated severe tricuspid regurgitation and improved right ventricular function toward normal, supporting an aggressive approach to important functional tricuspid regurgitation.