Effective atomic number of paraspinal muscles is associated with acute vertebral fracture risk.

OBJECTIVES: To investigate the relations among effective atomic number (Zeff), density, and area of paraspinal muscles, volumetric BMD (vBMD), and acute vertebral fractures (VF) by using spectral base images (SBIs) and routine CT images. METHODS: A total of 223 patients (52 men and 171 women) with acute VF and seven hundred and seventy-six subjects (286 men and 390 women) without VF of at least 60 years were enrolled and underwent dual-layer detector CT scans. We quantified the cross-sectional area (paraSMA), density (paraSMD) and Zeff of paraspinal muscles by CT images and SBIs and measured vBMD of the lumbar spine by quantitative CT. RESULTS: Higher vBMD was associated with lower VF risk in both sexes (adjusted OR, 0.33 and 0.43). After adjusting for age and BMI, the associations of ParaSMD with VF were not significant in men, and in women the association was borderline significant (OR, 0.80; 95% CI, 0.64 to 1.00). However, higher Zeff of paraspinal muscles was associated with lower VF risk in men (adjusted OR, 0.59; 0.36 to 0.96) but not in women. The associations of all muscle indexes with VF were not significant after further adjusting for vBMD. CONCLUSIONS: A higher Zeff of paraspinal muscles is associated with lower VF risk in older men but not in older women. The density, area and Zeff of paraspinal muscles were not vBMD independent risk factors for acute VF. ADVANCES IN KNOWLEDGE: The effective atomic number of paraspinal muscles might be a potential marker for vertebral fracture risk prediction.

Enhanced CD95 and interleukin 18 signalling accompany T cell receptor Vß21.3+ activation in multi-inflammatory syndrome in children.

Multisystem inflammatory syndrome in children is a post-infectious presentation SARS-CoV-2 associated with expansion of the T cell receptor Vß21.3+ T-cell subgroup. Here we apply muti-single cell omics to compare the inflammatory process in children with acute respiratory COVID-19 and those presenting with non SARS-CoV-2 infections in children. Here we show that in Multi-Inflammatory Syndrome in Children (MIS-C), the natural killer cell and monocyte population demonstrate heightened CD95 (Fas) and Interleuking 18 receptor expression. Additionally, TCR Vß21.3+ CD4+ T-cells exhibit skewed differentiation towards T helper 1, 17 and regulatory T cells, with increased expression of the co-stimulation receptors ICOS, CD28 and interleukin 18 receptor. We observe no functional evidence for NLRP3 inflammasome pathway overactivation, though MIS-C monocytes show elevated active caspase 8. This, coupled with raised IL18 mRNA expression in CD16- NK cells on single cell RNA sequencing analysis, suggests interleukin 18 and CD95 signalling may trigger activation of TCR Vß21.3+ T-cells in MIS-C, driven by increased IL-18 production from activated monocytes and CD16- Natural Killer cells.

Short-duration selective decontamination of the digestive tract infection control does not contribute to increased antimicrobial resistance burden in a pilot cluster randomised trial (the ARCTIC Study).

OBJECTIVE: Selective decontamination of the digestive tract (SDD) is a well-studied but hotly contested medical intervention of enhanced infection control. Here, we aim to characterise the changes to the microbiome and antimicrobial resistance (AMR) gene profiles in critically ill children treated with SDD-enhanced infection control compared with conventional infection control. DESIGN: We conducted shotgun metagenomic microbiome and resistome analysis on serial oropharyngeal and faecal samples collected from critically ill, mechanically ventilated patients in a pilot multicentre cluster randomised trial of SDD. The microbiome and AMR profiles were compared for longitudinal and intergroup changes. Of consented patients, faecal microbiome baseline samples were obtained in 89 critically ill children. Additionally, samples collected during and after critical illness were collected in 17 children treated with SDD-enhanced infection control and 19 children who received standard care. RESULTS: SDD affected the alpha and beta diversity of critically ill children to a greater degree than standard care. At cessation of treatment, the microbiome of SDD patients was dominated by Actinomycetota, specifically Bifidobacterium, at the end of mechanical ventilation. Altered gut microbiota was evident in a subset of SDD-treated children who returned late longitudinal samples compared with children receiving standard care. Clinically relevant AMR gene burden was unaffected by the administration of SDD-enhanced infection control compared with standard care. SDD did not affect the composition of the oral microbiome compared with standard treatment. CONCLUSION: Short interventions of SDD caused a shift in the microbiome but not of the AMR gene pool in critically ill children at the end mechanical ventilation, compared with standard antimicrobial therapy.

Bio-Inspired Network for Diagnosing Liver Steatosis in Ultrasound Images.

Using ultrasound imaging to diagnose liver steatosis is of great significance for preventing diseases such as cirrhosis and liver cancer. Accurate diagnosis under conditions of low quality, noise and poor resolutions is still a challenging task. Physiological studies have shown that the visual cortex of the biological visual system has selective attention neural mechanisms and feedback regulation of high features to low features. When processing visual information, these cortical regions selectively focus on more sensitive information and ignore unimportant details, which can effectively extract important features from visual information. Inspired by this, we propose a new diagnostic network for hepatic steatosis. In order to simulate the selection mechanism and feedback regulation of the visual cortex in the ventral pathway, it consists of a receptive field feature extraction module, parallel attention module and feedback connection. The receptive field feature extraction module corresponds to the inhibition of the non-classical receptive field of V1 neurons on the classical receptive field. It processes the input image to suppress the unimportant background texture. Two types of attention are adopted in the parallel attention module to process the same visual information and extract different important features for fusion, which improves the overall performance of the model. In addition, we construct a new dataset of fatty liver ultrasound images and validate the proposed model on this dataset. The experimental results show that the network has good performance in terms of sensitivity, specificity and accuracy for the diagnosis of fatty liver disease.

Multidimensional risk factor analysis of acute low back pain progressing to chronicity: a longitudinal cohort study protocol.

Introduction: Approximately 40% of patients with acute low back pain (LBP) develop chronic low back pain, which significantly increases the risk of poor prognosis. To reduce the risk of acute LBP becoming chronic, effective preventive strategies are needed. Early identification of risk factors for the development of chronic LBP can help clinicians choose appropriate treatment options and improve patient outcomes. However, previous screening tools have not considered medical imaging findings. The aim of this study is to identify factors that can predict the risk of acute LBP becoming chronic based on clinical information, pain and disability assessment, and MRI imaging findings. This protocol describes the methodology and plan for investigating multidimensional risk factors for acute LBP becoming chronic, in order to better understand the development of acute LBP and prevent chronic LBP. Methods: This is a prospective multicenter study. We plan to recruit 1,000 adult patients with acute low back pain from four centers. In order to select four representative centers, we find the larger hospitals from different regions in Yunnan Province. The study will use a longitudinal cohort design. Patients will undergo baseline assessments upon admission and will be followed up for 5 years to collect the time of chronicity and associated risk factors. Upon admission, patients will be collected detailed demographic information, subjective and objective pain scores, disability scale, and lumbar spine MRI scanning. In addition, patient's medical history, lifestyle, psychological factors will be collected. Patients will be followed up at 3 months, 6 months, 1 year, 2 years and up for 5 years after admission to collect the time of chronicity and associated factors. Multivariate analysis will be used to explore the multidimensional risk factors affecting the chronicity of acute LBP patients (such as age, gender, BMI, degree of intervertebral disc degeneration, etc.), and survival analysis will be performed to explore the impact of each factor on the time of chronicity. Ethics and dissemination: The study has been approved by the institutional research ethics committee of each study center (main center number: 2022-L-305). Results will be disseminated through scientific conferences and peer-reviewed publications, as well as meetings with stakeholders.

Deep Learning-Based Fully Automated Segmentation of Regional Muscle Volume and Spatial Intermuscular Fat Using CT.

RATIONALE AND OBJECTIVES: We aim to develop a CT-based deep learning (DL) system for fully automatic segmentation of regional muscle volume and measurement of the spatial intermuscular fat distribution of the gluteus maximus muscle. MATERIALS AND METHODS: A total of 472 subjects were enrolled and randomly assigned to one of three groups: a training set, test set 1, and test set 2. For each subject in the training set and test set 1, we selected six slices of the CT images as the region of interest for manual segmentation by a radiologist. For each subject in test set 2, we selected all slices of the gluteus maximus muscle on the CT images for manual segmentation. The DL system was constructed using Attention U-Net and the Otsu binary thresholding method to segment the muscle and measure the fat fraction of the gluteus maximus muscle. The segmentation results of the DL system were evaluated using the Dice similarity coefficient (DSC), Hausdorff distance (HD), and the average surface distance (ASD) as metrics. Intraclass correlation coefficients (ICCs) and Bland-Altman plots were used to assess agreement in the measurements of fat fraction between the radiologist and the DL system. RESULTS: The DL system showed good segmentation performance on the two test sets, with DSCs of 0.930 and 0.873, respectively. The fat fraction of the gluteus maximus muscle measured by the DL system was in agreement with the radiologist (ICC=0.748). CONCLUSION: The proposed DL system showed accurate, fully automated segmentation performance and good agreement with the radiologist at fat fraction evaluation, and can be further used for muscle evaluation.

Low thigh muscle strength in relation to myosteatosis in patients with type 2 diabetes mellitus.

This study aimed to investigate the association of thigh muscle fat infiltration by quantitative MRI with muscle strength in patients with type 2 diabetes mellitus (T2DM). Seventy T2DM patients and sixty control subjects (71 males; age: 52 ± 8 years) underwent 3.0T MRI and isokinetic muscle strength measurements to obtain the skeletal muscle index (SMI), intermuscular adipose tissue (IMAT) proton density fat fraction (PDFF), intramuscular fat (IMF) PDFF, peak torque (PT) and total work (TW) of knee extensors and flexors. The differences of measurements between T2DM patients and asymptomatic volunteers were compared. Multivariate regression analysis was used to determine significant predictors of thigh extension and flexion strength. The SMI, IMAT and IMF PDFF of thigh muscles in T2DM patients were higher than that in the control group (p < 0.001), while PT and TW were lower than those in the control subjects (p < 0.05). Both IMF and IMAT PDFF were negatively correlated with PT, TW in participants with T2DM (extensors: r = - 0.72, - 0.70, p < 0.001; r = - 0.62, - 0.56, p < 0.05. flexors: r = - 0.37, - 0.43, p < 0.05; r = - 0.39, - 0.46, p < 0.05). Moderate and strong correlations between HOMA-IR and muscle strength measurements, muscle PDFFs were observed in extensors and flexors. IMF PDFF and age were the statistically significant predictor of PT and TW of extensors of thigh in multivariate regression analysis. Therefore, the thigh muscle PDFF increased was associated with muscle strength decreased in T2DM patients beyond SMI. Age are also important factors influencing thigh muscle PDFF and strength in T2DM patients.

Deformation Mechanism and Control of In-Situ Assembling Caisson Technology in Soft Soil Area under Field Measurement and Numerical Simulation.

With urban space becoming much more crowded, the construction of underground spaces continues to expand to deeper, and the requirements for the large depth and minor deformation in urban engineering construction are getting more urgent. A new kind of in-situ assembling caisson technology (called VSM) is a vertical shaft method (VSM), which excavates the stratum under water with a mechanical arm and assembles the prefabricated caisson segments at the same time. This paper takes the Shanghai Zhuyuan Bailonggang Sewage Connecting Pipe Project as an example, which is the first construction project in the soft soil area, such as Shanghai, and makes a technical analysis of the VSM by comparing the field measurement and numerical simulation. Ground settlements and layered deep displacements were monitored in the field measurement during the VSM construction. It shows that the maximum ground settlement caused by the VSM is 15.2 mm and the maximum horizontal displacement is 3.74 mm. The influence range of the shaft excavation on the ground settlement is about 30 m away from the shaft center. The results demonstrate that the VSM construction has great applicability in the soft soil area. A finite element simulation model of the VSM shaft is established and verified by field measurement. There is a certain error between the traditional theoretical calculation by analogy to the common retaining walls of the deep foundation pit and the measured results, while the simulation results are relatively consistent with field measurements. The reasons for the difference are well-analyzed. Finally, the effects of the VSM construction method on the engineering environment are analyzed, and the suggestions for deformation control in the future are put forward.

The rapid detection of respiratory pathogens in critically ill children.

PURPOSE: Respiratory infections are the most common reason for admission to paediatric intensive care units (PICU). Most patients with lower respiratory tract infection (LRTI) receive broad-spectrum antimicrobials, despite low rates of bacterial culture confirmation. Here, we evaluated a molecular diagnostic test for LRTI to inform the better use of antimicrobials. METHODS: The Rapid Assay for Sick Children with Acute Lung infection Study was a single-centre, prospective, observational cohort study of mechanically ventilated children (> 37/40 weeks corrected gestation to 18 years) with suspected community acquired or ventilator-associated LRTI. We evaluated the use of a 52-pathogen custom TaqMan Array Card (TAC) to identify pathogens in non-bronchoscopic bronchoalveolar lavage (mini-BAL) samples. TAC results were compared to routine microbiology testing. Primary study outcomes were sensitivity and specificity of TAC, and time to result. RESULTS: We enrolled 100 patients, all of whom were tested with TAC and 91 of whom had matching culture samples. TAC had a sensitivity of 89.5% (95% confidence interval (CI95) 66.9-98.7) and specificity of 97.9% (CI95 97.2-98.5) compared to routine bacterial and fungal culture. TAC took a median 25.8 h (IQR 9.1-29.8 h) from sample collection to result. Culture was significantly slower: median 110.4 h (IQR 85.2-141.6 h) for a positive result and median 69.4 h (IQR 52.8-78.6) for a negative result. CONCLUSIONS: TAC is a reliable and rapid adjunct diagnostic approach for LRTI in critically ill children, with the potential to aid early rationalisation of antimicrobial therapy.

Edge detection networks inspired by neural mechanisms of selective attention in biological visual cortex.

Edge detection is of great importance to the middle and high-level vision task in computer vision, and it is useful to improve its performance. This paper is different from previous edge detection methods designed only for decoding networks. We propose a new edge detection network composed of modulation coding network and decoding network. Among them, modulation coding network is the combination of modulation enhancement network and coding network designed by using the self-attention mechanism in Transformer, which is inspired by the selective attention mechanism of V1, V2, and V4 in biological vision. The modulation enhancement network effectively enhances the feature extraction ability of the encoding network, realizes the selective extraction of the global features of the input image, and improves the performance of the entire model. In addition, we designed a new decoding network based on the function of integrating feature information in the IT layer of the biological vision system. Unlike previous decoding networks, it combines top-down decoding and bottom-up decoding, uses down-sampling decoding to extract more features, and then achieves better performance by fusing up-sampling decoding features. We evaluated the proposed method experimentally on multiple publicly available datasets BSDS500, NYUD-V2, and barcelona images for perceptual edge detection (BIPED). Among them, the best performance is achieved on the NYUD and BIPED datasets, and the second result is achieved on the BSDS500. Experimental results show that this method is highly competitive among all methods.

Association of Paraspinal Muscle CSA and PDFF Measurements With Lumbar Intervertebral Disk Degeneration in Patients With Chronic Low Back Pain.

There is an interaction between the lumbar spine and paraspinal muscles, which may play a role in the development of intervertebral disc (IVD) degeneration and may affect CLBP. The study aims to assess the relationship between IVD degeneration and paraspinal muscle fat infiltration in CLBP patients by quantitative MR imaging, and to evaluate the influence of sex and age on CLBP muscle fat infiltration. Sixty CLBP patients (46.3 years ±17.0) and thirty-two healthy subjects (44.9 years ±17.6) were recruited for this study. 3.0 T MRI was used to perform the sagittal and axial T1, T2 of the lumbar spine, and axial paraspinal muscle IDEAL imaging at the L4/5 and L5/S1 levels. Proton density fat fraction (PDFF) of the multifidus and erector spinae at two IVD levels were measured. The Pfirrmann grades of IVD degeneration, Oswestry Disability Index (ODI), and Visual Analog Scale (VAS) were also evaluated. Compare the cross-sectional area (CSA) and PDFF of the paraspinal muscles between CLBP patients and healthy subjects, and analyze the relationship between the muscle PDFF and Pfirrmann grades, gender, and age of CLBP patients. Compared with healthy subjects, the CSA of the multifidus muscle in CLBP patients decreased (1320.2±188.1mm2vs. 1228.7±191.0 mm2, p<0.05) at the L4/5 level, the average PDFF increased, (7.7±2.6% vs. 14.79±5.3%, 8.8±4.2% vs. 16.03±5.3%, all p<0.05) at both L4/5 and L5/S1 levels. The PDFF of paraspinal muscles were correlated with adjacent IVD degeneration, ODI and VSA in CLBP patients (all p<0.05). After using age and body mass index (BMI) as control variables, significance was retained (all p<0.05). Multiple regression analysis revealed sex and age also were significantly associated with multifidus PDFF (all p < 0.05). This study confirmed that the CSA decreased and the PDFF increased of the paraspinal muscles in CLBP patients. It reveals a significant correlation between the PDFF of CLBP paraspinal muscles and the grade of IVD degeneration. Sex and age are also important factors influencing CLBP paraspinal muscle infiltration.

Associations of Lumber Disc Degeneration With Paraspinal Muscles Myosteatosis in Discogenic Low Back Pain.

Accompanied with intervertebral disc (IVD) degeneration, increasing fat infiltration of paraspinal muscles may be related to discogenic low back pain (DLBP), but their relationship is still unclear and the classical animal models are not completely applicable. The purpose of this study was to assess the paraspinal muscle fat infiltration in patients with DLBP by quantitative MRI, and to develop a novel DLBP rat model to explore the potential relationship between DLBP paraspinal muscle fat infiltration and TNF-α levels. We measured the proton density fat fraction (PDFF) of the multifidus and erector spinae muscles of 70 DLBP patients and 36 healthy volunteers by using quantitative MRI IDEAL-IQ. In addition, we developed a DLBP experimental rat model by puncturing the L4/5 and L5/6 IVDs under the guidance of X-ray fluoroscopy. Then various behavioral experiments, MRI and pathological examination of IVDs were used to evaluate the performance of the DLBP animal model. The gait analysis, hot plate test, acetone test, grasping test and tail suspension test were used to evaluate the pain and muscle dysfunction in rats. Through quantitative MRI and histological examination, the degeneration of IVDs and fat infiltration in the muscles were observed in vivo and ex vivo. Enzyme linked immunosorbent assay detects the level of TNF-α in rat IVDs and paraspinal muscles. In the human study, compared with healthy volunteers, the PDFF of multifidus and erector muscles of DLBP patients increased significantly at L4/5 and L5/S1 levels (p<0.05). In the rat experiment, compared with control group and sham group, DLBP group had reduced gait score, shortened response time to cold and heat stimuli, prolonged bending time, and shortened struggling time. Rat lumbar MRI T2WI showed that the signal intensity of L4/5 and L5/6 IVDs were progressively decreased. Histological examination revealed that IVDs had increased collagen fibers, reduced nucleus pulposus, thickened annulus fibrosus, and distorted shape. The PDFF of multifidus muscle at L4/5 and L5/6 level in the DLBP group were more than that in other groups (p<0.05), and HE staining and oil red O staining of paraspinal muscles showed that the muscle bundle space of the DLBP group muscles increased, and the muscle tissues Increased lipid droplets. Finally, the expression of TNF-α in IVDs and paraspinal muscles in the DLBP group were significantly higher than that in the control group (p<0.05). It is reliable and feasible to establish a DLBP rat model by puncturing the lumbar IVDs under the guidance of X-ray fluoroscopy. The degeneration of lumbar IVDs with DLBP leads to the occurrence of fat infiltration of paraspinal muscles, which is related to the expression of TNF-α.

Rapid Assay for Sick Children with Acute Lung infection Study (RASCALS): diagnostic cohort study protocol.

INTRODUCTION: Lower respiratory tract infection (LRTI) is the most commonly treated infection in critically ill children. Pathogens are infrequently identified on routine respiratory culture, and this is a time-consuming process. A syndromic approach to rapid molecular testing that includes a wide range of bacterial and fungal targets has the potential to aid clinical decision making and reduce unnecessary broad spectrum antimicrobial prescribing. Here, we describe a single-centre prospective cohort study investigating the use of a 52-pathogen TaqMan array card (TAC) for LRTI in the paediatric intensive care unit (PICU). METHODS AND ANALYSIS: Critically ill children with suspected LRTI will be enrolled to this 100 patient single-centre prospective observational study in a PICU in the East of England. Samples will be obtained via routine non-bronchoscopic bronchoalveolar lavage which will be sent for standard microbiology culture in addition to TAC. A blood draw will be obtained via any existing vascular access device. The primary outcomes of the study will be (1) concordance of TAC result with routine culture and 16S rRNA gene sequencing and (2) time of diagnostic result from TAC versus routine culture. Secondary outcomes will include impact of the test on total antimicrobial prescriptions, a description of the inflammatory profile of the lung and blood in response to pneumonia and a description of the clinical experience of medical and nursing staff using TAC. ETHICS AND DISSEMINATION: This study has been approved by the Yorkshire and the Humber-Bradford Leeds Research Ethics Committee (REC reference 20/YH/0089). Informed consent will be obtained from all participants. Results will be published in peer-reviewed publications and international conferences. TRIAL REGISTRATION NUMBER: NCT04233268.

Muscular blood oxygen level-dependent MRI is beneficial to evaluate effectiveness of an exercise prescription.

BACKGROUND: To determine the feasibility and validity of using blood oxygen level-dependent (BOLD) magnetic resonance imaging (MRI) to evaluate the effects of back extension exercise on core lumbar paraspinal muscle strength. METHODS: In this prospective study, R2* and T2 mapping of paraspinal muscles of 100 healthy volunteers were performed before and after back extension exercises in different recovery sessions (session I, II, III or IV). Volunteers use the Roman chair to complete the back extension exercises. The cross-sectional area (CSA), R2* and T2 values were measured and analyzed in 3 muscles (iliocostalis, longissimus, and multifidus muscles) of the lower back before and after exercise. RESULTS: The CSA and T2 values of iliocostalis, longissimus, and multifidus muscles at L3 and L4 levels were higher in recovery sessions I and II than in the resting-state (P<0.05); however, compared to that in the resting-state, the R2* value was significantly reduced in session I but increased in sessions II-IV (P<0.05). Furthermore, the CSA and T2 values in recovery session I were higher than those in the resting-state, whereas the R2* value was lower (P<0.05). After exercise, the recovery tendency of R2* and T2 value was consistent in both males and females, but a significant sex difference in R2* value was observed between recovery sessions III and IV (P<0.05). CONCLUSIONS: R2* mapping and T2 mapping are effective and feasible for assessment of the effects of back extension exercises on lumbar paraspinal muscle strength.

Clinical utility of a computed tomography-based receiver operating characteristic curve model for the diagnosis of COVID-19.

BACKGROUND: The outbreak of COVID-19 poses a major and urgent threat to global public health. CT findings associated with COVID-19 pneumonia from initial diagnosis until patient recovery. This study aimed to retrospectively analyze abnormal lung changes following initial computed tomography (CT) among patients with coronavirus disease 2019 (COVID-19) in Yunnan, and to evaluate the effectiveness of a chest CT-based model for the diagnosis of COVID-19. METHODS: One hundred and nine patients with COVID-19 pneumonia confirmed with the positive new coronavirus nucleic acid antibody who exhibited abnormal findings on initial CT were retrospectively analyzed. Thereafter, changes in the number, distribution, shape, and density of the lesions were observed. Further, the epidemiological, clinical, and CT imaging findings (+/-) were correlated. Following univariate and multivariate logistic regression analysis, receiver operating characteristic (ROC) curves were generated for significant factors, and models were established to evaluate the diagnostic ability of CT for COVID-19. RESULTS: Our results showed significant differences between patients with COVID-19 in epidemiological history (first, second, and third generation), clinical type (moderate, severe, and critical), and abnormal CT imaging characteristics (+/-) (P<0.05). Moreover, significant differences in abnormal CT imaging characteristics, including region, extent, and focus, were observed between the first generation and the other generations (P<0.05). For the diagnosis of COVID-19, the areas under the ROC curves for logistic regression models 1, 2, and 3 were 0.8016 (95% CI: 0.6759-0.9274), 0.9132 (95% CI: 0.8571-0.9693), and 0.9758 (95% CI: 0.9466-1), respectively. CONCLUSIONS: The ROC curve regression model based on chest CT signs displayed a high diagnostic value for COVID-19.

Dynamic changes in chest CT findings of patients with coronavirus disease 2019 (COVID-19) in different disease stages: a multicenter study.

BACKGROUND: To investigate the dynamic changes in high-resolution computed tomography (HRCT) findings of coronavirus disease 2019 (COVID-19) patients with different severities in different disease stages. METHODS: We retrospectively collected the clinical and imaging data of 96 patients in Yunnan Province, China, who were diagnosed with COVID-19 between January 22 and March 15, 2020. Based on disease severity, the COVID-19 patients were classified into four types: mild (n=15), moderate (n=59), severe (n=19), and critical (n=3). Based on hospital stay and number of computed tomography (CT) scans, the clinical/disease course was divided into four stages, including stage 1 (days 0-4), stage 2 (days 5-9), stage 3 (days 10-14), and stage 4 (days 15-19). The HRCT findings, CT value, and lesion volume were analyzed for each stage and compared among the four stages of COVID-19 patients. RESULTS: CT findings were negative over the four stages for all mild COVID-19 patients. More lesions were found in the peripheral lung fields than in peripheral + central fields (P<0.05), and the number of negative patients in stage 4 were more than those in stages 1-3 (P<0.05). The left and right lower lobe were the most frequently affected lobes (P<0.05). In moderate patients, round ground glass opacities (GGOs) decreased from stage 1 to stage 4; partial consolidation peaked in stage 2 and then decreased in stages 3-4; fibrous stripes and subpleural lines increased from stage 1 and peaked in stage 4. Partial consolidation and consolidation were more common in severe patients than in moderate patients over the disease course (P<0.05). Critical patients showed significant partial consolidation and consolidation; The CT value, lesion volume and lesion volume percentage significantly decreased from stages 1-2 to stage 4 (all P<0.05). CONCLUSIONS: The dynamic changes in lung HRCT images are clinically related to the disease course of COVID-19.

CT-based radiomics combined with signs: a valuable tool to help radiologist discriminate COVID-19 and influenza pneumonia.

BACKGROUND: In this COVID-19 pandemic, the differential diagnosis of viral pneumonia is still challenging. We aimed to assess the classification performance of computed tomography (CT)-based CT signs and radiomics features for discriminating COVID-19 and influenza pneumonia. METHODS: A total of 154 patients with confirmed viral pneumonia (COVID-19: 89 cases, influenza pneumonia: 65 cases) were collected retrospectively in this study. Pneumonia signs and radiomics features were extracted from the initial unenhanced chest CT images to build independent and combined models. The predictive performance of the radiomics model, CT sign model, the combined model was constructed based on the whole dataset and internally invalidated by using 1000-times bootstrap. Diagnostic performance of the models was assessed via receiver operating characteristic (ROC) analysis. RESULTS: The combined models consisted of 4 significant CT signs and 7 selected features and demonstrated better discrimination performance between COVID-19 and influenza pneumonia than the single radiomics model. For the radiomics model, the area under the ROC curve (AUC) was 0.888 (sensitivity, 86.5%; specificity, 78.4%; accuracy, 83.1%), and the AUC was 0.906 (sensitivity, 86.5%; specificity, 81.5%; accuracy, 84.4%) in the CT signs model. After combining CT signs and radiomics features, AUC of the combined model was 0.959 (sensitivity, 89.9%; specificity, 90.7%; accuracy, 90.3%). CONCLUSIONS: CT-based radiomics combined with signs might be a potential method for distinguishing COVID-19 and influenza pneumonia with satisfactory performance.

Bisphenol A alters volatile fatty acids accumulation during sludge anaerobic fermentation by affecting amino acid metabolism, material transport and carbohydrate-active enzymes.

Bisphenol A (BPA), a typical persistent organic pollutant in waste activated sludge, was chosen to explore its influence on the accumulation of volatile fatty acids (VFAs), which is an important raw material, during anaerobic fermentation. BPA in the range of 0-200 mg/kg dry sludge was beneficial to VFAs production, from 1564 mg chemical oxygen demand (COD)/L in the control to 2095 mg COD/L with 50 mg/kg BPA; the acetic acid yield was 563 and 1010 mg COD/L with 0 and 50 mg/kg BPA, respectively. The abundance of microorganisms that can consume VFAs was reduced and those responsible for producing VFAs was increased by BPA. Homologous genes of related enzymes in the pathways for amino acid metabolism, fatty acid biosynthesis, ABC transporters and quorum sensing were enhanced in the presence of BPA. The abundance of carbohydrate-active enzymes increased with BPA when compared with the control, benefitting VFAs production.

Volatile fatty acids production from waste activated sludge during anaerobic fermentation: The effect of superfine sand.

Superfine sand in waste activated sludge (WAS) increased the uncertainty of anaerobic fermentation. Experiments showed that VFAs production from WAS was positively affected by superfine sand, with an increase from 2513 mg COD/L in the control (without superfine sand) to 3002 mg COD/L with superfine sand. A mechanism study demonstrated that the main factor responsible for the improved VFAs accumulation in response to superfine sand was acetic acid, which increased by nearly 30%. Further investigation exhibited that the process of solubilization and acidification were facilitated by superfine sand and the abundance of anaerobic functional microorganisms was greatly increased. Moreover, the activities of acetate kinase (AK) as well as the quantity of AK encoding gene were greatly promoted by superfine sand. The heat release during WAS anaerobic fermentation with superfine sand was higher than that without superfine sand (25.8 × 10-3 versus 24.7 × 10-3 W·min at about 70 min).

Galacto-conjugation of Navitoclax as an efficient strategy to increase senolytic specificity and reduce platelet toxicity.

Pharmacologically active compounds with preferential cytotoxic activity for senescent cells, known as senolytics, can ameliorate or even revert pathological manifestations of senescence in numerous preclinical mouse disease models, including cancer models. However, translation of senolytic therapies to human disease is hampered by their suboptimal specificity for senescent cells and important toxicities that narrow their therapeutic windows. We have previously shown that the high levels of senescence-associated lysosomal ß-galactosidase (SA-ß-gal) found within senescent cells can be exploited to specifically release tracers and cytotoxic cargoes from galactose-encapsulated nanoparticles within these cells. Here, we show that galacto-conjugation of the BCL-2 family inhibitor Navitoclax results in a potent senolytic prodrug (Nav-Gal), that can be preferentially activated by SA-ß-gal activity in a wide range of cell types. Nav-Gal selectively induces senescent cell apoptosis and has a higher senolytic index than Navitoclax (through reduced activation in nonsenescent cells). Nav-Gal enhances the cytotoxicity of standard senescence-inducing chemotherapy (cisplatin) in human A549 lung cancer cells. Concomitant treatment with cisplatin and Nav-Gal in vivo results in the eradication of senescent lung cancer cells and significantly reduces tumour growth. Importantly, galacto-conjugation reduces Navitoclax-induced platelet apoptosis in human and murine blood samples treated ex vivo, and thrombocytopenia at therapeutically effective concentrations in murine lung cancer models. Taken together, we provide a potentially versatile strategy for generating effective senolytic prodrugs with reduced toxicities.