Severity-associated markers and assessment model for predicting the severity of COVID-19: a retrospective study in Hangzhou, China.

BACKGROUND: The severity of COVID-19 associates with the clinical decision making and the prognosis of COVID-19 patients, therefore, early identification of patients who are likely to develop severe or critical COVID-19 is critical in clinical practice. The aim of this study was to screen severity-associated markers and construct an assessment model for predicting the severity of COVID-19. METHODS: 172 confirmed COVID-19 patients were enrolled from two designated hospitals in Hangzhou, China. Ordinal logistic regression was used to screen severity-associated markers. Least Absolute Shrinkage and Selection Operator (LASSO) regression was performed for further feature selection. Assessment models were constructed using logistic regression, ridge regression, support vector machine and random forest. The area under the receiver operator characteristic curve (AUROC) was used to evaluate the performance of different models. Internal validation was performed by using bootstrap with 500 re-sampling in the training set, and external validation was performed in the validation set for the four models, respectively. RESULTS: Age, comorbidity, fever, and 18 laboratory markers were associated with the severity of COVID-19 (all P values < 0.05). By LASSO regression, eight markers were included for the assessment model construction. The ridge regression model had the best performance with AUROCs of 0.930 (95% CI, 0.914-0.943) and 0.827 (95% CI, 0.716-0.921) in the internal and external validations, respectively. A risk score, established based on the ridge regression model, had good discrimination in all patients with an AUROC of 0.897 (95% CI 0.845-0.940), and a well-fitted calibration curve. Using the optimal cutoff value of 71, the sensitivity and specificity were 87.1% and 78.1%, respectively. A web-based assessment system was developed based on the risk score. CONCLUSIONS: Eight clinical markers of lactate dehydrogenase, C-reactive protein, albumin, comorbidity, electrolyte disturbance, coagulation function, eosinophil and lymphocyte counts were associated with the severity of COVID-19. An assessment model constructed with these eight markers would help the clinician to evaluate the likelihood of developing severity of COVID-19 at admission and early take measures on clinical treatment.

All-optical interrogation of brain-wide activity in freely swimming larval zebrafish.

We introduce an all-optical technique that enables volumetric imaging of brain-wide calcium activity and targeted optogenetic stimulation of specific brain regions in unrestrained larval zebrafish. The system consists of three main components: a 3D tracking module, a dual-color fluorescence imaging module, and a real-time activity manipulation module. Our approach uses a sensitive genetically encoded calcium indicator in combination with a long Stokes shift red fluorescence protein as a reference channel, allowing the extraction of Ca2+ activity from signals contaminated by motion artifacts. The method also incorporates rapid 3D image reconstruction and registration, facilitating real-time selective optogenetic stimulation of different regions of the brain. By demonstrating that selective light activation of the midbrain regions in larval zebrafish could reliably trigger biased turning behavior and changes of brain-wide neural activity, we present a valuable tool for investigating the causal relationship between distributed neural circuit dynamics and naturalistic behavior.

Streptococcus parasuis, an Emerging Zoonotic Pathogen, Possesses the Capacity to Induce Cerebral Inflammatory Responses.

To date, three Streptococcus parasuis strains, BS26, BS27, and NN1, have been isolated from the blood cultures of patients with peritonitis, pneumonia, and arthritis, indicating that S. parasuis is an emerging threat to susceptible people. There is thus an urgent need to further evaluate the pathogenesis of S. parasuis clinical strains in order to design efficient anti-inflammatory strategies. Our previous study demonstrated the capacity of S. parasuis clinical strains to enter the central nervous system (CNS) of infected mice. However, the characteristics and inflammatory mechanism of CNS infections caused by S. parasuis are still non-available. In the present study, we investigated the proportion and time of two clinical S. parasuis strains NN1 and BS26 infected mice that developed neurological symptoms. The characteristics of histopathological changes and the cerebral immune response in mice with neurological symptoms were analyzed. Furthermore, we evaluated the roles of microglia and astrocytes in the S. parasuis clinical strain-induced cerebral inflammation. Our data indicated that S. parasuis clinical strains possess a high potential to induce cerebral inflammation in susceptible people at the early phase of infection. Our study contributes to increasing the understanding of the pathogenicity of S. parasuis and the inflammatory mechanisms of the brain against infection caused by S. parasuis.

Effects of Core Stabilization Training on the Cobb Angle and Pulmonary Function in Adolescent Patients with Idiopathic Scoliosis.

Objective: To observe the effects of core stabilization training on the Cobb angle, respiratory muscle strength (maximum inspiratory pressure, MIP; maximal expiratory pressure, MEP), and pulmonary function (forced vital capacity, FVC; forced expiratory volume, FEV1.0; FEV1.0/FVC%) in adolescent patients with idiopathic scoliosis (AIS) and offer practical-based evidence for the rehabilitation treatment for AIS patients. Methods: 36 AIS patients were assigned to the core stability training (CST) group (n = 18) and control group (n = 18); the CST group participated in three sessions of core stabilization exercise per week for 12 weeks and the control group did not perform regular physical training during 12 weeks of study. Then, the Cobb angle, respiratory muscle strength (MIP and MEP), and pulmonary function (FVC, FEV1.0, and FEV1.0/FVC%) were measured before and after core stabilization training. Results: After 12 weeks of core stabilization training, compared with the pretest, the Cobb angle showed a significant decrease, FVC, FEV1, MIP, and MEP a significant increase (P < 0.01 respectively), and there was no statistical difference in FEV1/FVC in the CST group; there was no significant difference (P > 0.05 respectively) before and after an experiment in the control group except MEP decreased significantly (P < 0.01, P < 0.05). After 12 weeks of core stabilization training, compared with the control group, the Cobb angle significantly decreased (P < 0.01), FVC, FEV1, MIP, and MEP significantly increased (P < 0.05 respectively) in the CST group, but there was no significant difference (P > 0.05, respectively) in FEV1/FVC between the control group and CST group. Conclusions: Core stabilization exercise can be considered to have a positive effect on the normal physiological curvature of the spine in AIS patients, as it decreases the Cobb angle and strengthens respiratory muscle strength and pulmonary function.

Characterization of integrative and conjugative elements carrying antibiotic resistance genes of Streptococcus suis isolated in China.

Streptococcus suis, an emerging zoonotic pathogen, is important reservoirs of antibiotic resistance genes that play critical roles in the horizontal transfer of corresponding resistances. In the present study, 656 antibiotic resistance (AR) genes were detected in 154 of 155 genomes of S. suis strains isolated from the nasopharynx of slaughtered pigs and the lungs of diseased pigs in China. The AR genes were clustered into 11 categories, consisting of tetracycline, macrolides, lincosamide, streptogramin, aminoglycoside, trimethoprim, amphenicols, nucleoside, quinupristin/dalfopristin, glycopeptide, and oxazolidinones resistance genes. In order to investigate the transmission patterns of the AR genes, AR genes-associated the mobile genetic elements (MGEs) were extracted and investigated. Twenty ICEs, one defective ICE, one tandem ICE, and ten prophages were found, which mainly carried tetracycline, macrolides/lincosamides/streptogramin (MLS), and aminoglycosides resistance genes. Three types of DNA cargo with AR genes were integrated into specific sites of ICEs: integrative mobilizable elements (IMEs), cis-IMEs (CIMEs), and transposon Tn916. Obvious differences in AR gene categories were found among the three cargo types. IMEs mainly harbored tetracycline and MLS resistance genes. CIMEs mainly carried aminoglycoside resistance genes, while transposon Tn916 carried only the tet (M) gene. Nearly all AR genes in ICEs were carried by IMEs and CIMEs. IMEs were prevalent and were also detected in additional 29 S. suis genomes. The horizontal transfer of IMEs and CIMEs may play critical role in ICE evolution and AR gene transmission in the S. suis population. Our findings provide novel insights into the transmission patterns of AR genes and the evolutionary mechanisms of ICEs in S. suis.

Comparative transcriptomic analysis reveal genes involved in the pathogenicity increase of Streptococcus suis epidemic strains.

Streptococcus suis epidemic strains were responsible for two outbreaks in China and possessed increased pathogenicity which was featured prominently by inducing an excessive inflammatory response at the early phase of infection. To discover the critical genes responsible for the pathogenicity increase of S. suis epidemic strains, the genome-wide transcriptional profiles of epidemic strain SC84 were investigated at the early phase of interaction with BV2 cells. The overall low expression levels of 89K pathogenicity island (PAI) and 129 known virulence genes in the SC84 interaction groups indicated that its pathogenicity increase should be attributed to novel mechanisms. Using highly pathogenic strain P1/7 and intermediately pathogenic strain 89-1591 as controls, 11 pathogenicity increase crucial genes (PICGs) and 38 pathogenicity increase-related genes (PIRGs) were identified in the SC84 incubation groups. The PICGs encoded proteins related to the methionine biosynthesis/uptake pathway and played critical roles in the pathogenicity increase of epidemic strains. A high proportion of PIRGs encoded surface proteins related to host cell adherence and immune escape, which may be conducive to the pathogenicity increase of epidemic strains by rapidly initiating infection. The fact that none of PICGs and PIRGs belonged to epidemic strain-specific gene indicated that the pathogenicity increase of epidemic strain may be determined by the expression level of genes, rather than the presence of them. Our results deepened the understanding on the mechanism of the pathogenicity increase of S. suis epidemic strains and provided novel approaches to control the life-threatening infections of S. suis epidemic strains.