Traditional Chinese medicine invigorating the spleen and kidney promotes HBsAg seroclearance in the mouse model.

Traditional Chinese medicine (TCM) is often used as an adjuvant or alternative therapy for abnormal liver biochemistry or liver fibrosis associated with chronic hepatitis B (CHB). However, the role of TCM in HBsAg seroclearance remains unclear. We aimed at exploring the role and possible mechanisms of TCM in HBsAg seroclearance. Fifteen widely used TCM granules invigorating the spleen and kidneys were screened. C57BL/6J mice were administered daily with TCM granules by gavage for 1 week. The effect of TCM on the M1 polarization of macrophages was measured using a CD86 assay. According to the principles of formulating prescriptions, three single TCM with the most noticeable effect on M1 polarization, accompanied by two other TCM granules, were used to develop a TCM formula. The hepatitis B virus-expressing mouse model was constructed by hydrodynamic injection of the pAAV/HBV1.2 plasmid. Hepatitis B virus-expressing mice were gavaged daily with phosphate-buffered saline (PBS), TCM formula, or Codonopsis Radix, for 1 week. HBsAg, HBeAg, and hepatitis B virus DNA levels were measured. In addition, gut microbiota was profiled using 16S rDNA sequencing. Several TCM granules showed significant effects on M1 polarization. The TCM formula accelerated HBsAg seroclearance compared with the Codonopsis Radix and PBS groups. Intrahepatic M1 polarization, as indicated by flow cytometry and immunohistochemistry, was induced in the TCM formula and Codonopsis Radix groups. The abundance of Alloprevotella significantly increased in the TCM formula and Codonopsis Radix groups. These results demonstrate that the TCM formula for invigorating the spleen and kidney can accelerate HBsAg seroclearance. This effect can be attributed, at least in part, to M1 polarization of intrahepatic macrophages.

US LI-RADS in surveillance for recurrent hepatocellular carcinoma after curative treatment.

OBJECTIVES: To investigate the performance of US LI-RADS in surveillance for recurrent hepatocellular carcinoma (RHCC) after curative treatment. MATERIALS AND METHODS: This study enrolled 644 patients between January 2018 and August 2018 as a derivation cohort, and 397 patients from September 2018 to December 2018 as a validation cohort. The US surveillance after HCC curative treatment was performed. The US LI-RADS observation categories and visualization scores were analyzed. Four criteria using US LI-RADS or Alpha-fetoprotein (AFP) as the surveillance algorithm were evaluated. The sensitivity, specificity, and negative predictive value (NPV) were calculated. RESULTS: A total of 212 (32.9%) patients in derivation cohort and 158 (39.8%) patients in validation cohort were detected to have RHCCs. The criterion of US-2/3 or AFP ≥ 20 µg/L had higher sensitivity (derivation, 96.7% vs 92.9% vs 81.1% vs 90.6%; validation, 96.2% vs 90.5% vs 80.4% vs 89.9%) and NPV (derivation, 95.7% vs 93.3% vs 88.0% vs 91.8%; validation, 94.6% vs 89.4% vs 83.6% vs 89.0%), but lower specificity (derivation, 35.9% vs 48.2% vs 67.6% vs 51.9%; validation, 43.5% vs 52.7% vs 66.1% vs 54.0%) than criterion of US-2/3, US-3, and US-3 or AFP ≥ 20 µg/L. Analysis of the visualization score subgroups confirmed that the sensitivity (89.2-97.6% vs 81.0-83.3%) and NPV(88.4-98.0% vs 80.0-83.3%) of score A and score B groups were higher than score C group in criterion of US-2/3 in both two cohorts. CONCLUSIONS: In the surveillance for RHCC, US LI-RADS with AFP had a high sensitivity and NPV when US-2/3 or AFP ≥ 20 µg/L was considered a criterion. CLINICAL RELEVANCE STATEMENT: The criterion of US-2/3 or AFP ≥ 20 µg/L improves sensitivity and NPV for RHCC surveillance, which provides a valuable reference for patients in RHCC surveillance after curative treatment. KEY POINTS: • US LI-RADS with AFP had high sensitivity and NPV in surveillance for RHCC when considering US-2/3 or AFP ≥ 20 µg/L as a criterion. • After US with AFP surveillance, patients with US-2/3 or AFP ≥ 20 µg/L should perform enhanced imaging for confirmative diagnosis. Patients with US-1 or AFP < 20 µg/L continue to repeat US with AFP surveillance. • Patients with risk factors for poor visualization scores limited the sensitivity of US surveillance in RHCC.

Screening and verification of antiviral compounds against HSV-1 using a method based on a plaque inhibition assay.

BACKGROUND: Herpes simplex virus type 1 (HSV-1) infection is a common viral disease that mainly causes oral lesions, but can also cause genital lesions in some instances. Current treatments with nucleoside analogs are limited by the emergence of drug resistance. Therefore, novel anti-HSV-1 drugs are urgently needed. METHODS: In this study, we screened a library of 2080 compounds for anti-HSV-1 activity using a plaque formation assay. We selected 11 potential inhibitors of HSV-1 and further evaluated their antiviral effects by plaque reduction assay and real-time polymerase chain reaction (qPCR). RESULTS: Five compounds, namely ginsenoside Rd, brassinolide, rosamultin, 3'-hydroxy puerarin, and clinafloxacin HCl, showed potent anti-HSV-1 activity and completely suppressed plaque formation at a concentration of 10 µM. Among them, clinafloxacin HCl, a fluoroquinolone antibiotic, exhibited a high selectivity index for HSV-1. CONCLUSIONS: Our findings suggest that these five compounds have potential antiviral properties against HSV-1 and may have different mechanisms of action. Further studies are warranted to elucidate the antiviral mechanisms of these compounds and to explore their therapeutic potential for HSV-1 infection.

Type I IFNs repolarized a CD169+ macrophage population with anti-tumor potentials in hepatocellular carcinoma.

Macrophages constitute a major component in human hepatocellular carcinoma (HCC) and perform various functions to facilitate disease progression. Reprogramming or reconstituting the tumor surveillance phenotypes of macrophages represents an attractive immunotherapeutic strategy in cancer treatments. The current study identified CD169 as a potential target for macrophage repolarization since it signified a population of macrophages positively correlated with an activated immune signature and better prognosis of patients with HCC. In vitro experiments revealed that a low dose of type I interferon (IFN) could effectively reprogram human monocyte-derived macrophages to upregulate CD169 expression, and such induced CD169+ macrophages exhibited significantly enhanced phagocytotic and CD8+ T cell-activating capacities compared to controls. A low dose of IFNα also inhibited hepatoma growth in mice in vivo, presumably through polarizing the CD169+ macrophage population and enhancing CD8+ T cell activities. Notably, IFNα also induced substantial PD-L1 expression on macrophages in vivo, and thus blockade of PD-L1 could further increase the anti-tumor efficacy of IFNα in the treatment of HCC. We propose a low dose of IFNα in combination with a PD-L1 blocking agent as a potential anti-tumor therapeutic strategy via its effects on macrophage polarization.

Strategy for Accurate Diagnosis by Contrast-Enhanced Ultrasound of Focal Liver Lesions in Patients Not at High Risk for Hepatocellular Carcinoma: A Preliminary Study.

OBJECTIVE: To develop an effective strategy for accurate diagnosis of focal liver lesions (FLLs) in patients with non-high risk for hepatocellular carcinoma (HCC). METHODS: From January 2012 to December 2015, consecutive patients with non-high risk for HCC who underwent contrast-enhanced ultrasound (CEUS) were included in this retrospective double-reader study. All patients were stratified into 2 different risks (intermediate, low-risk) groups according to criteria based on clinical characteristics, known as clinical risk stratification criteria. For the intermediate-risk group, the CEUS criteria for identifying benign lesions and HCCs were constructed based on selected CEUS features. The diagnostic performance of the clinical risk stratification criteria, and CEUS criteria for identifying benign lesions and HCCs was evaluated. RESULTS: This study included 348 FLLs in 348 patients. The sensitivity and specificity of the clinical risk stratification criteria for malignancy was 97.8 and 69.8%. Patients were classified as intermediate risk if they were male, or older than 40 years of age, or HBcAb positive, or having positive tumor markers. Otherwise, patients were classified as low risk. Among the 348 patients, 327 were in the intermediate-risk group and 21 were in the low-risk group. In the intermediate-risk group, the CEUS criteria for identifying benign lesions were any of the following features: 1) hyper/isoenhancement in the arterial phase without washout, 2) nonenhancement in all phases, 3) peripheral discontinuous globular enhancement in the arterial phase, 4) centrifugal enhancement or peripheral enhancement followed by no central enhancement, or 5) enhanced septa. The accuracy, sensitivity, and specificity of the CEUS criteria for identifying benign lesions were 94.5, 83.0, and 99.6%, respectively. Arterial phase hyperenhancement followed by mild and late washout (>60 seconds) was more common in HCC patients than in non-HCC patients (P < .001). Using arterial phase hyperenhancement followed by mild and late washout as the CEUS criteria for identifying HCCs, the sensitivity and specificity were 52.6 and 95.3%, but unfortunately, the positive predictive value was only 82.0%. For the low-risk group, no further analysis was performed due to the small sample size. CONCLUSIONS: Initial clinical risk stratification followed by assessment of certain CEUS features appears to be a promising strategy for the accurate diagnosis of FLLs in patients not at high risk for HCC.

Anti-Virulence Strategy of Novel Dehydroabietic Acid Derivatives: Design, Synthesis, and Antibacterial Evaluation.

Anti-virulence strategies are attractive and interesting strategies for controlling bacterial diseases because virulence factors are fundamental to the infection process of numerous serious phytopathogenics. To extend the novel anti-virulence agents, a series of dehydroabietic acid (DAA) derivatives decorated with amino alcohol unit were semi-synthesized based on structural modification of the renewable natural DAA and evaluated for their antibacterial activity against Xanthomonas oryzae pv. oryzae (Xoo), Xanthomonas axonopodis pv. citri (Xac), and Pseudomonas syringae pv. actinidiae (Psa). Compound 2b showed the most promising antibacterial activity against Xoo with an EC50 of 2.7 µg mL-1. Furthermore, compound 2b demonstrated remarkable control effectiveness against bacterial leaf blight (BLB) in rice, with values of 48.6% and 61.4% for curative and protective activities. In addition, antibacterial behavior suggested that compound 2b could suppress various virulence factors, including EPS, biofilm, swimming motility, and flagella. Therefore, the current study provided promising lead compounds for novel bactericides discovery by inhibiting bacterial virulence factors.

Genome-Wide Association Study Identifies Resistance Loci for Bacterial Blight in a Collection of Asian Temperate Japonica Rice Germplasm.

Growing resistant rice cultivars is the most effective strategy to control bacterial blight (BB), a devastating disease caused by Xanthomonas oryzae pv. oryzae (Xoo). Screening resistant germplasm and identifying resistance (R) genes are prerequisites for breeding resistant rice cultivars. We conducted a genome-wide association study (GWAS) to detect quantitative trait loci (QTL) associated with BB resistance using 359 East Asian temperate Japonica accessions inoculated with two Chinese Xoo strains (KS6-6 and GV) and one Philippine Xoo strain (PXO99A). Based on the 55K SNPs Array dataset of the 359 Japonica accessions, eight QTL were identified on rice chromosomes 1, 2, 4, 10, and 11. Four of the QTL coincided with previously reported QTL, and four were novel loci. Six R genes were localized in the qBBV-11.1, qBBV-11.2, and qBBV-11.3 loci on chromosome 11 in this Japonica collection. Haplotype analysis revealed candidate genes associated with BB resistance in each QTL. Notably, LOC_Os11g47290 in qBBV-11.3, encoding a leucine-rich repeat receptor-like kinase, was a candidate gene associated with resistance to the virulent strain GV. Knockout mutants of Nipponbare with the susceptible haplotype of LOC_Os11g47290 exhibited significantly improved BB resistance. These results will be useful for cloning BB resistance genes and breeding resistant rice cultivars.

Covalently Targeted Highly Conserved Tyr318 to Improve the Drug Resistance Profiles of HIV-1 NNRTIs: A Proof-of-Concept Study.

This study presents proof of concept for designing a novel HIV-1 covalent inhibitor targeting the highly conserved Tyr318 in the HIV-1 non-nucleoside reverse transcriptase inhibitors binding pocket to improve the drug resistance profiles. The target inhibitor ZA-2 with a fluorosulfate warhead in the structure was found to be a potent inhibitor (EC50 = 11-246 nM) against HIV-1 IIIB and a panel of NNRTIs-resistant strains, being far superior to those of NVP and EFV. Moreover, ZA-2 was demonstrated with lower cytotoxicity (CC50 = 125 µM). In the reverse transcriptase inhibitory assay, ZA-2 exhibited an IC50 value of 0.057 µM with the ELISA method, and the MALDI-TOF MS data demonstrated the covalent binding mode of ZA-2 with the enzyme. Additionally, the molecular simulations have also demonstrated that compounds can form covalent binding to the Tyr318.

Optimal exercise to improve physical ability and performance in older adults with sarcopenia: a systematic review and network meta-analysis.

OBJECTIVE: The study aimed to pool and analyze the effects of different forms of exercise on muscle strength (handgrip strength [HGS]), and physical performance (timed up and go test [TUGT], gait speed [GS] and chair stand test [CS]) in older adults with sarcopenia. METHODS: The effect sizes of all studies retrieved and included by the four databases were analyzed using the network meta-analysis and expressed as standardized mean differences (SMD) and the corresponding 95% confidence intervals (CI). RESULTS: Twenty studies were included in this study with 1347 older adults with sarcopenia. Compared with control and other intervention groups, resistance training (RT) improved HGS [SMD=3.8, 95% CI (1.3, 6.0), p<0.05] and TUGT [SMD = -1.99, 95% CI (-2.82, -1.16), p<0.05] significantly. comprehensive training (CT) [SMD = -2.04, 95% CI (-3.05, -1.06), Pp<0.05] and Comprehensive training under self-management (CT_SM) [SMD = -2.01, 95% CI (-3.24, -0.78), p<0.05] improved TUGT significantly. CONCLUSION: In older adults with sarcopenia, RT could improve HGS and TUGT, CT and CT_SM could improve TUGT. There were no significant changes in CS and GS with any of the exercise training modes.

Comparative transcriptome and miRNA analysis of skin pigmentation during embryonic development of Chinese soft-shelled turtle (Pelodiscus sinensis).

BACKGROUND: Aquatic animals show diverse body coloration, and the formation of animal body colour is a complicated process. Increasing evidence has shown that microRNAs (miRNAs) play important regulatory roles in many life processes. The role of miRNAs in pigmentation has been investigated in some species. However, the regulatory patterns of miRNAs in reptile pigmentation remain to be elucidated. In this study, we performed an integrated analysis of miRNA and mRNA expression profiles to explore corresponding regulatory patterns in embryonic body colour formation in the soft-shelled turtle Pelodiscus sinensis. RESULTS: We identified 8 866 novel genes and 9 061 mature miRNAs in the skin of Chinese soft-shelled turtles in three embryonic stages (initial period: IP, middle period: MP, final period: FP). A total of 16 563 target genes of the miRNAs were identified. Furthermore, we identified 2 867, 1 840 and 4 290 different expression genes (DEGs) and 227, 158 and 678 different expression miRNAs (DEMs) in IP vs. MP, MP vs. FP, and IP vs. FP, respectively. Among which 72 genes and 25 miRNAs may be related to turtle pigmentation in embryonic development. Further analysis of the novel miRNA families revealed that some novel miRNAs related to pigmentation belong to the miR-7386, miR-138, miR-19 and miR-129 families. Novel_miR_2622 and novel_miR_2173 belong to the miR-19 family and target Kit and Gpnmb, respectively. The quantification of novel_miR_2622 and Kit revealed negative regulation, indicating that novel_miR_2622 may participate in embryonic pigmentation in P. sinensis by negatively regulating the expression of Kit. CONCLUSIONS: miRNA act as master regulators of biological processes by controlling the expression of mRNAs. Considering their importance, the identified miRNAs and their target genes in Chinese soft-shelled turtle might be useful for investigating the molecular processes involved in pigmentation. All the results of this study may aid in the improvement of P. sinensis breeding traits for aquaculture.

LR-M Observations on Contrast-Enhanced Ultrasound: Detection of Hepatocellular Carcinoma Using Additional Features in Comparison With Current LI-RADS Criteria.

BACKGROUND. Contrast-enhanced ultrasound (CEUS) LI-RADS assigns category LR-M to observations that are definitely or probably malignant but that on imaging are not specific for hepatocellular carcinoma (HCC). A high percentage of LR-M observations represent HCC. OBJECTIVE. The purpose of this study was to retrospectively evaluate the utility of additional features, beyond conventional LI-RADS major features, for detecting HCC among LR-M observations on CEUS. METHODS. This retrospective study included 174 patients (145 men, 29 women; mean age, 53 years) at high risk of HCC who underwent CEUS from August 2014 to June 2016 that showed an LR-M observation according to CEUS LI-RADS version 2017. Two radiologists independently assessed CEUS images for major features and four additional features (chaotic vessels, peripheral circular artery, clear boundary of tumor enhancement, clear boundary of intratumoral unenhanced area). The diagnostic performance of four proposed criteria for the detection of HCC among LR-M observations was assessed. The impact of criteria based on the additional findings on detection of HCC was further explored. Histology or composite imaging and clinical follow-up were the reference standards. RESULTS. The 174 LR-M observations included 142 HCCs and 32 non-HCC lesions (20 intrahepatic cholangiocarcinomas, five combined hepatocellular-cholangiocarcinomas, seven benign lesions). Interreader agreement on the additional features ranged from κ = 0.65 to κ = 0.88. Two of the additional features had excellent PPV for HCC: chaotic vessels (94.8%) and peripheral circular arteries (98.1%). The presence of either of these two additional features had sensitivity of 50.7%, specificity of 90.6%, PPV of 96.0%, and NPV of 29.3% for HCC. Three other criteria incorporating variations of major LI-RADS features but not the additional features had sensitivities of 55.6-96.5%, specificities of 49.6-68.8%, PPVs of 87.8-90.6%, and NPVs of 25.0-75.0%. On the basis of criteria that included additional features, 75 of 174 LR-M observations were recategorized LR-5; 72 of the 75 were HCC. CONCLUSION. The presence of chaotic vessels and/or peripheral circular artery had high specificity and PPV for HCC among LR-M observations. Other explored criteria based on major features did not have higher specificity or PPV. CLINICAL IMPACT. Clinical adoption of the additional CEUS features could help establish the diagnosis of HCC noninvasively and avoid the need for biopsy of LR-M observations.

Hb New York, preliminary results concerning the hematologic characteristics and the effects on thalassemia.

BACKGROUND: The hematological phenotype and genotype analysis of hemoglobin New York (Hb New York) combined with α or ß thalassemia has been rarely reported, and whether there is any effect of Hb New York on thalassemia has not been well explored. METHODS AND RESULTS: In this study, peripheral blood samples from 346 Hb New York carriers were collected for blood cell parameter analysis. When comparing Hb New York heterozygotes, Hb New York combined with α0 thalassemia or α+ thalassemia, we found that the differences in hemoglobin (HGB), MCV and MCH values were statistically significant (P < 0.05). The HGB, MCV and MCH values of α thalassemia patients were not different from Hb New York combined with α thalassemia group (P > 0.05). When Hb New York heterozygotes were compared to Hb New York combined with ß0 thalassemia or ß+ thalassemia, the differences in MCV and MCH values were statistically significant (P < 0.05). However, the differences in MCV and MCH values were not statistically significant between Hb New York combined with ß thalassemia and ß thalassemia (P > 0.05). CONCLUSIONS: Our study shows that the hematological characteristics of Hb New York combined with thalassemia are similar to the corresponding thalassemia, and Hb New York does not aggravate the clinical manifestations of thalassemia.

Contrast-Enhanced Ultrasound for Differentiation Between Poorly Differentiated Hepatocellular Carcinoma and Intrahepatic Cholangiocarcinoma.

PURPOSE: To evaluate the diagnostic performance of LR-5 for diagnosing poorly differentiated hepatocellular carcinoma (p-HCC). To build a contrast-enhanced ultrasound (CEUS) signature for improving the differential diagnostic performance between p-HCC and intrahepatic cholangiocarcinoma (ICC). METHODS: The B-mode ultrasound (BUS) and CEUS features of 60 p-HCCs and 56 ICCs were retrospectively analyzed. The CEUS LI-RADS category was assigned according to CEUS LI-RADS v2017. A diagnostic CEUS signature was built based on the independent significant features. An ultrasound (US) signature combining both BUS and CEUS features was also built. The diagnostic performances of the CEUS signature, US signature, and LR-5 were evaluated by receiver operating characteristic (ROC) analysis. RESULTS: One (1.7%) p-HCC and 26 (46.4%) ICC patients presented cholangiectasis or cholangiolithiasis (P < .001). Fifty-four (90.0%) p-HCCs and 8 (14.3%) ICCs showed clear boundaries in the artery phase (P < .001). The washout times of p-HCCs and ICCs were 81.0 ± 42.5 s and 34.7 ± 8.6 s, respectively (P < .001). The AUC, sensitivity, and specificity of the CEUS signature, US signature, and LR-5 were 0.955, 91.67%, and 90.57% versus 0.976, 96.67%, and 92.45% versus 0.758, 51.67%, and 100%, respectively. The AUC and sensitivity of CEUS LI-RADS were much lower than those of the CEUS and US signatures (P < .001). CONCLUSION: LR-5 had high specificity but low sensitivity in diagnosing p-HCC. When the washout time and tumor boundary were included in the CEUS signature, the sensitivity and AUC were remarkably increased in the differentiation between p-HCC and ICC.

Using new criteria to improve the differentiation between HCC and non-HCC malignancies: clinical practice and discussion in CEUS LI-RADS 2017.

PURPOSE: Using contrast-enhanced ultrasound (CEUS) to evaluate the diagnostic performance of liver imaging reporting and data system (LI-RADS) version 2017 and to explore potential ways to improve the efficacy. METHODS: A total of 315 nodules were classified as LR-1 to LR-5, LR-M, and LR-TIV. New criteria were applied by adjusting the early washout onset (< 45 s) and the time of marked washout (within 3 min). Two subgroups of the LR-M nodules were recategorized as LR-5, respectively. The diagnostic performance was evaluated by calculating the accuracy, sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV). RESULTS: By adjusting early washout onset to < 45 s, the LR-5 as a standard for diagnosing HCC had an improved sensitivity (74.1% vs. 56.1%, P < 0.001) without significant change in PPV (93.3% vs. 96.1%, P = 0.267), but the specificity was decreased (48.3% vs. 78.5%, P = 0.018). The LR-M as a standard for the diagnosis of non-HCC malignancies had an increase in specificity (89.2% vs. 66.2%, P < 0.001) but a decrease in sensitivity (31.5% vs. 68.4%, P = 0.023). After reclassification according to the time of marked washout, the sensitivity of the LR-5 increased (80% vs. 56.1%, P < 0.001) without a change in PPV (94.9% vs. 96.1%, P = 0.626) and specificity (80% vs. 78.5%, P = 0.879). For reclassified LR-M nodules, the specificity increased (87.5% versus 66.2%, P < 0.001) with a non-significant decrease in sensitivity (47.3% vs. 68.4%, P = 0.189). CONCLUSIONS: The CEUS LI-RADS showed good confidence in diagnosing HCC while tended to misdiagnose HCC as non-HCC malignancies. Adjusting the marked washout time within 3 min would reduce the possibility of this misdiagnosis.

Effects of nitrogen dioxide exposure on the risk of eye and adnexa diseases among children in Shenzhen, China: an assessment using the generalized additive modeling approach.

This study aimed to assess the relationship between nitrogen dioxide (NO2) exposure and the risk of eye and adnexa diseases (EADs) among children in Shenzhen, China. Information about the daily number of outpatients with EADs and the concentration of air pollutants and meteorological data were collected. A generalized additive model was used to assess the effect of NO2 exposure on the risk of EADs during outpatient visits. An increase in NO2 level by 10 µg/m3 was related to an increase in the daily number of outpatients by 5.43% (95% confidence interval [CI]: 2.25%, 8.70%) at lag0, by 4.35% (95% CI: 1.15%, 7.66%) at lag1, and by 3.21% (95% CI: 0.05%, 6.47%) at lag3. In addition, the relationship between NO2 exposure and the risk of dacryoadenitis was the strongest, with an estimated value of 15.0% (95% CI: 7.99%, 22.5%) at lag0. Moreover, the association between NO2 exposure and the risk of EADs among children in Shenzhen was confirmed in this study. Therefore, the government should introduce stringent environmental policies to control air pollution and protect human health, particularly that of the vulnerable population.

Goal or Miss? A Bernoulli Distribution for In-Game Outcome Prediction in Soccer.

Due to a colossal soccer market, soccer analysis has attracted considerable attention from industry and academia. In-game outcome prediction has great potential in various applications such as game broadcasting, tactical decision making, and betting. In some sports, the method of directly predicting in-game outcomes based on the ongoing game state is already being used as a statistical tool. However, soccer is a sport with low-scoring games and frequent draws, which makes in-game prediction challenging. Most existing studies focus on pre-game prediction instead. This paper, however, proposes a two-stage method for soccer in-game outcome prediction, namely in-game outcome prediction (IGSOP). When the full length of a soccer game is divided into sufficiently small time frames, the goal scored by each team in each time frame can be modeled as a random variable following the Bernoulli distribution. In the first stage, IGSOP adopts state-based machine learning to predict the probability of a scoring goal in each future time frame. In the second stage, IGSOP simulates the remainder of the game to estimate the outcome of a game. This two-stage approach effectively captures the dynamic situation after a goal and the uncertainty in the late phase of a game. Chinese Super League data have been used for algorithm training and evaluation, and the results demonstrate that IGSOP outperforms existing methods, especially in predicting draws and prediction during final moments of games. IGSOP provides a novel perspective to solve the problem of in-game outcome prediction in soccer, which has a potential ripple effect on related research.

Global burden of acute viral hepatitis and its association with socioeconomic development status, 1990-2019.

BACKGROUND & AIMS: Acute viral hepatitis (AVH) represents an important global health problem; however, the progress in understanding AVH is limited because of the priority of combating persistent HBV and HCV infections. Therefore, an improved understanding of the burden of AVH is required to help design strategies for global intervention. METHODS: Data on 4 major AVH types, including acute hepatitis A, B, C, and E, excluding D, were collected by the Global Burden of Disease (GBD) 2019 database. Age-standardized incidence rates and disability-adjusted life year (DALY) rates for AVH were extracted from GBD 2019 and stratified by sex, level of socio-demographic index (SDI), country, and territory. The association between the burden of AVH and socioeconomic development status, as represented by the SDI, was described. RESULTS: In 2019, there was an age-standardized incidence rate of 3,615.9 (95% CI 3,360.5-3,888.3) and an age-standardized DALY rate of 58.0 (47.3-70.0) per 100,000 person-years for the 4 major types of AVH. Among the major AVH types, acute hepatitis A caused the heaviest burden. There was a significant downward trend in age-standardized DALY rates caused by major incidences of AVH between 1990 and 2019. In 2019, regions or countries located in West and East Africa exhibited the highest age-standardized incidence rates of the 4 major AVH types. These rates were stratified by SDI: high SDI and high-middle SDI locations recorded the lowest incidence and DALY rates of AVH, whereas the low-middle SDI and low SDI locations showed the highest burden of AVH. CONCLUSIONS: The socioeconomic development status and burden of AVH are associated. Therefore, the GBD 2019 data should be used by policymakers to guide cost-effective interventions for AVH. LAY SUMMARY: We identified a negative association between socioeconomic development status and the burden of acute viral hepatitis. The lowest burden of acute viral hepatitis was noted for rich countries, whereas the highest burden of acute viral hepatitis was noted for poor countries.

A solvent-assisted ESIPT fluorescent dye for F-/Ag+ sensing and high-resolution imaging of the cilia in live cells.

A solvent-assisted ESIPT fluorescent dye was synthesized and used as a probe (2-PPN) for the detection of F-/Ag+ and high-resolution imaging of the cilia in live cells. The developed ESIPT fluorophore exhibited strong tautomeric fluorescence in protic solvents and normal emission in aprotic solvents, which is a significant departure from that of conventional intramolecular ESIPT compounds. The H-binding interaction of F- and the chelation of Ag+ with the ESIPT module of 2-PPN resulted in significant tautomeric emission quenching. From this basis, the 2-PPN-based assays for the detection of F- and Ag+ were established. The detection limit for F- and Ag+ sensing is 2.4 nM and 1.5 nM, respectively. The selective experimental results showed that no tautomeric fluorescence change of 2-PPN could be observed in the presence of the other inorganic ions in the same medium, revealing high selectivity of 2-PPN to F- and Ag+. Furthermore, MTT assay experiments proved that the probe 2-PPN exhibited low cytotoxicity and good cell membrane permeability. The probe was also further successfully utilized to image the cilia in vitro MCF7 cells, displaying its high-resolution imaging performance.Graphical abstract.

Association between the uric acid and hypertension in community-based Chinese population: stratified analysis based on body mass index and age.

Many studies have shown that uric acid was related to hypertension. However, the association dependence on body mass index (BMI) or age was unclear. This study was performed with a group of 4012 Chinese population aged 30 to 92 years old. Subjects were divided into four groups according to the quartiles of uric acid (UA) concentration [First group: ≤ 231 µmol/L (reference), Second group: 231-289 µmol/L, Third group: 289-362 µmol/L, Fourth group: > 362 µmol/L]. Hypertension was defined as newly measured blood pressure ≥ 140/90 mmHg or taking antihypertensive drugs. Stratified analysis based on BMI (< 28 kg/m2 vs ≥ 28 kg/m2) and age (< 60 years old vs ≥ 60 years old) to analyze the association between UA and hypertension. Subjects were 54.50 (45.00, 63.00) years old, and 40.98% were male, 38.33% were hypertension. Adjusted odds ratios (95% confidence intervals) for the association of UA and hypertension were 2.226 (1.662, 2.980), 4.340 (3.253, 5.790), 5.898 (4.434, 7.845) and 6.557 (4.927, 8.727) in the four groups among ≥ 60 years old respectively comparing with first group among < 60 years old. Adjusted odds ratios (95% confidence intervals) for the association between UA and hypertension were 2.170 (1.236, 3.808), 5.260 (3.267, 8.468), 9.056 (5.509, 14.888) and 3.730 (2.529, 5.550) in the four groups among BMI ≥ 28 kg/m2 respectively comparing with first group among BMI < 28 kg/m2. Uric acid was significantly associated with the hypertension. The association was stronger among subjects ≥ 60 years old or BMI ≥ 28 kg/m2.

Association of serum VLDL level with hyperhomocysteinemia in hypertensive patients: A cross-sectional study.

BACKGROUND: Increasing evidence suggests that hyperhomocysteinemia (HHcy) and hyperlipidemia have been recognized as two independent risks for cardiovascular disease. However, the association between hyperlipidemia and HHcy in hypertensive patients has not been systemically elucidated. The aim of this study was to investigate the relation between very low-density lipoprotein (VLDL) and HHcy in hypertensive patients. METHODS: From July 2013 to March 2014, a large cross-sectional study was performed using 4012 participants from urban and rural communities in Hunan province, China. Participants underwent accurate assessment of lipid profiles, homocysteine (Hcy), anthropometric, blood pressure, and other biochemical indicators. RESULTS: Among 1257 participants with hypertension, 626 (49.80%) were men and 631 (50.20%) were women. In total, 1081 (86.00%) of the participants were found to have HHcy, of which 559 (44.47%) were men and 522 (41.53%) were women. In the univariate analysis, the OR for patients with hypertension associated with hyperhomocysteinemia was significantly enhanced as the quartiles of the Log VLDL were increased. OR for quartile 4 was significantly higher than that for quartile 1 (OR = 3.7, 95% CI: 2.6-5.1; P< .001). Additional adjustment for the confounding variables did not reduce the ORs for the association between the Log VLDL and hypertension associated with hyperhomocysteinemia (OR = 3.8, 95% CI: 2.7-5.5; P< .001; OR = 4.3, 95% CI: 1.6-11.8; P= .004, respectively). We also conducted analyses with Log VLDL as a continuous variable. Each unit increase in the Log VLDL was associated with the 1.3-fold increased risk of hypertension associated with hyperhomocysteinemia (95% CI: 1.9-2.9; P< .001). Adjusting for Cr, TG, TC, and HDL did not affect the relationship. CONCLUSIONS: Our data indicate that the Log VLDL concentrations appear to be an independent contributor to hypertension associated with hyperhomocysteinemia, even after adjusting for age and other covariables. The utility of the Log VLDL as a diagnostic, prognostic, and therapeutic indicator for the disease warrants further investigation. ABBREVIATIONS: HHcy: hyperhomocysteinemia; Hcy: homocysteine; VLDL: very low-density lipoprotein; CVD: cardiovascular disease; SBP: systolic blood pressure; DBP: diastolic blood pressure; BMI: body mass index; ALT: alanine aminotransferase; Cr: creatinine; UA: uric acid; TG: triglycerides; TC: total cholesterol; HDL: high-density lipoprotein; LDL: low-density lipoprotein; FBG: fasting blood glucose; CRP: C-reactive protein; MTHFR: methylene tetrahydrofolate reductase; NO: nitric oxide; HDL-C: high-density lipoprotein cholesterol.