Ultrasound Viscosity Imaging in Breast Lesions: A Multicenter Prospective Study.

RATIONALE AND OBJECTIVES: To explore and validate the clinical value of ultrasound (US) viscosity imaging in differentiating breast lesions by combining with BI-RADS, and then comparing the diagnostic performances with BI-RADS alone. MATERIALS AND METHODS: This multicenter, prospective study enrolled participants with breast lesions from June 2021 to November 2022. A development cohort (DC) and validation cohort (VC) were established. Using histological results as reference standard, the viscosity-related parameter with the highest area under the receiver operating curve (AUC) was selected as the optimal one. Then the original BI-RADS would upgrade or not based on the value of this parameter. Finally, the results were validated in the VC and total cohorts. In the DC, VC and total cohorts, all breast lesions were divided into the large lesion, small lesion and overall groups respectively. RESULTS: A total of 639 participants (mean age, 46 years ± 14) with 639 breast lesions (372 benign and 267 malignant lesions) were finally enrolled in this study including 392 participants in the DC and 247 in the VC. In the DC, the optimal viscosity-related parameter in differentiating breast lesions was calculated to be A'-S2-Vmax, with the AUC of 0.88 (95% CI: 0.84, 0.91). Using > 9.97 Pa.s as the cutoff value, the BI-RADS was then modified. The AUC of modified BI-RADS significantly increased from 0.85 (95% CI: 0.81, 0.88) to 0.91 (95% CI: 0.87, 0.93), 0.85 (95% CI: 0.80, 0.89) to 0.90 (95% CI: 0.85, 0.93) and 0.85 (95% CI: 0.82, 0.87) to 0.90 (95% CI: 0.88, 0.92) in the DC, VC and total cohorts respectively (P < .05 for all). CONCLUSION: The quantitative viscous parameters evaluated by US viscosity imaging contribute to breast cancer diagnosis when combined with BI-RADS.

Relationship between baseline mean platelet volume (MPV) and prognosis of patients with acute mild cerebral infarction undergoing intravenous thrombolysis with Alteplase.

Objective: To investigate the relationship between baseline, mean platelet volume (MPV) and prognosis of patients with acute mild cerebral infarction undergoing intravenous thrombolysis with alteplase. Methods: A retrospective analysis was conducted of clinical imaging and laboratory data of patients with acute mild cerebral infarction who received intravenous thrombolytic therapy with alteplase in Baoding No.1 Central Hospital between March 2018 and March 2021. According to mRS scores after three months, a total of 140 patients were divided into the good prognosis group(n=115) (mRS score

Downregulation of lncRNA XIST may promote Th17 differentiation through KDM6A-TSAd pathway in neuromyelitis optica spectrum disorders.

BACKGROUNDS: Neuromyelitis optica spectrum disorder (NMOSD) is an autoimmune disease with significant female preponderance. X inactive specific transcript (XIST) is a long non-coding RNA (lncRNA) and a key regulator of X-chromosome inactivation which is related to the sex-bias of autoimmunity. And Th17 cell proportion was significantly elevated in NMOSD according to our previous study. OBJECTIVES: This study aimed to explore the expression levels of lncRNA XIST-KDM6A-TSAd pathway in lymphocytes of female NMOSD patients, and investigate its possible relationship with pathogenesis of NMOSD. METHODS AND RESULTS: The study enrolled 30 acute-phase untreated female NMOSD patients and 30 age-matched female healthy controls, their lymphocytes were collected for experiments. Microarray as well as validation experiments showed lncRNA XIST was significantly downregulated in the NMOSD group. And the levels of lysine demethylase 6A (KDM6A) decreased in NMOSD and showed significant positive correlation with XIST. The levels of T cell-specific adapter (TSAd) mRNA and protein levels were significantly lower in NMOSD. And Chromatin immunoprecipitation assay demonstrated that NMOSD had more H3K27me3 modification than control at TSAd promoter region. CONCLUSIONS: The present study introduced a potential pathway that following lncRNA XIST downregulation, which process may promote Th17 differentiation in NMOSD. These findings shed new light on the immune regulation mechanism about lncRNA XIST and related epigenetic features, which may contribute to develop female-specific treatment plans.

Decreased SIRT1 mRNA expression in peripheral blood mononuclear cells from patients with neuromyelitis optica spectrum disorders.

OBJECTIVE: Sirtuin (SIRT)1, as a molecular link between immunity and metabolic pathways, is a key immune response regulator. The significance of SIRT1 in peripheral blood mononuclear cells (PBMCs) of neuromyelitis optica spectrum disorder (NMOSD) has not been investigated. Here, we aimed to evaluate the SIRT1 mRNA level in PBMCs of patients with NMOSD and its clinical relevance and explore the potential mechanism of SIRT1 action. METHODS: A total of 65 patients with NMOSD and 60 normal controls from North China were enrolled. Using real-time fluorescence quantitative-polymerase chain reaction, mRNA levels were detected in PBMCs, and protein levels were detected using western blotting. RESULTS: Compared to the healthy controls and chronic-phase patients with NMOSD, SIRT1 mRNA and protein levels in PBMCs of NMOSD patients with acute attack were significantly downregulated (p < 0.0001). ∆EDSS scores (EDSS scores in the acute phase-EDSS scores before the recent attack) were higher in NMOSD patients with low SIRT1 mRNA level than in patients with high SIRT1 expression (p = 0.042). SIRT1 mRNA level in patients with acute-phase NMSOD was positively correlated with lymphocyte and monocyte counts and negatively correlated with neutrophil counts and the neutrophil-to-lymphocyte ratio. Furthermore, the transcription factor FOXP3 mRNA level was significantly positively correlated with the SIRT1 mRNA level in PBMCs of patients with acute-phase NMOSD. CONCLUSIONS: Our study indicated that SIRT1 mRNA expression was downregulated in the PBMCs of patients with acute-phase NMOSD, and its level was correlated with the clinical parameters of the patients, suggesting a potential role of SIRT1 in NMOSD.

miR-485 regulates Th17 generation and pathogenesis in experimental autoimmune encephalomyelitis through targeting STAT3.

Experimental autoimmune encephalomyelitis (EAE) is an induced autoimmune disease widely used as an animal model for multiple sclerosis, which is mainly characterized by demyelination, axonal loss, as well as neurodegeneration of central nervous system (CNS). T-helper (Th) 17 cell that generate interleukin-17 (IL-17) plays a key role in its pathogenesis. Their activity and differentiation are tightly regulated by some cytokines and transcription factors. Certain microRNAs (miRNAs) are involved in the pathogenesis of various autoimmune disorders, including EAE. Our research detected a novel miRNA that can regulate EAE. According to the results, during EAE, the expression of miR-485 notably lowered, and STAT3 was significantly increased. It was discovered that miR-485 knockdown in vivo upregulated Th17-associated cytokines and aggravated EAE, while the overexpressed miR-485 down-regulated Th17-associated cytokines and mitigated EAE. The up-regulation of miRNA-485 in vitro inhibited Th17-associated cytokines expression within EAE CD4+ T cells. Furthermore, as revealed by target prediction and dual-luciferase reporter assays, miR-485 directly targets STAT3, a gene that encodes a protein responsible for Th17 generation. Overall, miR-485 exert vital functions in Th17 generation and EAE pathogenesis.

Secreted aminoacyl-tRNA synthetase-interacting multifunctional protein-1 (AIMP1) is a promising predictor for the severity of acute AQP4-IgG positive neuromyelitis optica spectrum disorder.

BACKGROUND AND OBJECTIVES: Aminoacyl-tRNA synthetase complex interacting with multifunctional protein-1 (AIMP1) has been reported to carry pro-inflammatory properties and anti-angiogenesis effects. However, the exact role of AIMP1 in patients with NMOSD is not yet clear. Our objective was to investigate the relationship between plasma AIMP1 levels and disease severity in patients with AQP4-IgG+ NMOSD from North China based on the Expanded Disability Status Scale (EDSS) score. METHODS: Plasma AIMP1 levels were measured using ELISA kits in 94 patients with AQP4-IgG+NMOSD (48 in the acute phase before high-dose intravenous methylprednisolone (IVMP) therapy, 21 in the acute phase after IVMP therapy, 25 in the clinical remission-phase)as well as 33 healthy controls (HCs). The disability function of NMOSD patients was evaluated using the EDSS score. Furthermore, the clinical characteristics of the patients were also evaluated, and laboratory tests were performed on blood samples. RESULTS: The plasma AIMP1 levels in AQP4-IgG+NMOSD patients with acute phase before IVMP therapy were significantly higher as compared to those in patients after the IVMP therapy (p < 0.001) as well as those in the clinical remission phase (p = 0.021) or HCs (p < 0.001). Plasma AIMP1 levels were positively correlated with EDSS scores (r = 0.485, p < 0.001) and negatively correlated with serum complement 3 concentrations (r =-0.452, p = 0.001). AIMP1 exhibited the potential to distinguish NMOSD from HCs (AUROC 0.820, p < 0.0001) and could differentiate mild and moderate-severe NMOSD (AUROC 0.790, p = 0.0006). Furthermore, plasma AIMP1 levels of ≥49.55pg/mL were found to be an independent predictor of the risk for moderate-severe NMOSD (with OR 0.03, 95%CI 0.001-0.654, p = 0.026). CONCLUSION: AIMP1 may be involved in the pathogenesis of AQP4-IgG+NMOSD disease and predict the disease activity, severity, or effect of treatment in patients with NMOSD. Further studies should be performed to reveal the precise mechanisms of AQP4-IgG+NMOSD.

Combined enhancement of the propionyl-CoA metabolic pathway for efficient androstenedione production in Mycolicibacterium neoaurum.

BACKGROUND: The production of androstenedione (AD) from phytosterols by Mycolicibacterium neoaurum is a multi-step biotransformation process, which requires degradation of sterol side chains, accompanied by the production of propionyl-CoA. However, the transient production of large amounts of propionyl-CoA can accumulate intracellularly to produce toxic effects and severely inhibit AD production. RESULTS: In the present study, the intracellular propionyl-CoA concentration was effectively reduced and the productivity of the strain was improved by enhancing the cytosolic methyl-branched lipid synthesis pathway and increasing the expression level of nat operator gene, respectively. Subsequently, the application of a pathway combination strategy, combined and the inducible regulation strategy, further improved AD productivity with a maximum AD conversion rate of 96.88%, an increase of 13.93% over the original strain. CONCLUSIONS: Overall, we provide a new strategy for reducing propionyl-CoA stress during biotransformation for the production of AD and other steroidal drugs using phytosterols.

Injection of Matrix Metalloproteinase-9 Leads to Ventricular Remodeling.

Objective: Previous studies have found that some ventricular remodeling is accompanied by increased matrix metalloproteinase-9 (MMP-9) in vivo, and MMP-9 inhibitors can reduce ventricular remodeling. However, there is still no direct evidence that MMP-9 causes ventricular remodeling. In this study, MMP-9 was injected into rats to observe whether MMP-9 caused ventricular remodeling, thereby providing direct evidence of MMP-9-induced ventricular remodeling. Methods: Forty-eight eight-week-old male Wistar rats were randomly divided, by weight, into control, low-, medium-, and high-dose MMP-9 groups and were administered normal saline or recombinant rat MMP-9 0.7, 1.4, or 2.1 ng/g, respectively, via intraperitoneal injection, twice per week. On the 28th day, six rats were randomly selected from each group (Stage I). The remaining rats continued receiving injections until the 56th day (Stage II). Echocardiography was performed to observe cardiac structure and function, and the left ventricular mass index (LVWI) was calculated. Myocardial pathological changes and the collagen volume fraction (CVF) were observed by HE and VG staining in myocardial tissue. MMP-9 levels in serum were tested using ELISA. Myocardial MMP-9 levels were measured using Western blots, and the myocardial expression levels of MMP-9 mRNA were assessed using RT-PCR. Results: During Stage I, serum MMP-9 and myocardial MMP-9 mRNA levels are increased; hypertrophic cardiomyocytes, disorderly arrangement of fibers, and endochylema dissolution are observed in the medium- and high-dose groups. The left ventricular weight index (LVWI) and myocardial MMP-9 increased, and the collagen volume fraction (CVF) reduced in the high-dose group. In Stage II, the left ventricular end-diastolic volume (LVEDV) and diameter (LVIDd) are higher, and CVF decreased in the medium- and high-dose groups. Myocardial pathological lesions intensified. Serum MMP-9 in the model groups and myocardial MMP-9 in the medium- and high-dose groups are increased. Conclusions: Injection of MMP-9 can lead to ventricular remodeling.

Application of the CRISPR/Cas System in Pathogen Detection: A Review.

Early and rapid diagnosis of pathogens is important for the prevention and control of epidemic disease. The polymerase chain reaction (PCR) technique requires expensive instrument control, a special test site, complex solution treatment steps and professional operation, which can limit its application in practice. The pathogen detection method based on the clustered regularly interspaced short palindromic repeats (CRISPRs) and CRISPR-associated protein (CRISPR/Cas) system is characterized by strong specificity, high sensitivity and convenience for detection, which is more suitable for practical applications. This article first reviews the CRISPR/Cas system, and then introduces the application of the two types of systems represented by Type II (cas9), Type V (cas12a, cas12b, cas14a) and Type VI (cas13a) in pathogen detection. Finally, challenges and prospects are proposed.

Personality and brain contribute to academic achievements of medical students.

There are many factors that influence the academic achievements of medical students, but how personality and brain modulate the academic achievements of medical students remains unclear. The study collected the personality, brain imaging, and academic data from 448 medical students at Tianjin Medical University with admission time between 2008 and 2017. Four types of academic achievements, including behavioral and social sciences, clinical sciences and skills, basic biomedical sciences, and scientific methods, were assessed by the academic records of 58 courses. Personality was evaluated by Tridimensional Personality Questionnaire and Neuroticism Extraversion Openness Personality Inventory. Brain structural and functional properties, including gray matter volume, spontaneous brain activity and functional connectivity, were computed based on magnetic resonance imaging (MRI). Linear regression was used to evaluate the associations between personality and academic achievements. A voxel-wise correlation was used to identify areas of the brain where structural and functional properties were associated with academic achievements. Mediation analysis was used to test whether brain properties and personality independently contribute to academic achievements. Our results showed that novelty seeking (NS) was negatively correlated, and conscientiousness was positively correlated with all types of academic achievements. Brain functional properties showed negatively correlated with academic achievement in basic biomedical sciences. However, we did not find any mediation effect of the brain functional properties on the association between personality (NS and conscientiousness) and academic achievement in basic biomedical sciences, nor mediation effect of the personality (NS and conscientiousness) on the association between brain functional properties and academic achievement in basic biomedical sciences. These findings suggest that specific personality (NS and conscientiousness) and brain functional properties independently contribute to academic achievements in basic biomedical sciences, and that modulation of these properties may benefit academic achievements among medical students.

Altered non-coding RNA profiles and potential disease marker identification in peripheral blood mononuclear cells of patients with NMOSD.

Neuromyelitis optica spectrum disorder (NMOSD) is an inflammatory demyelination disorder, and dysregulation of RNAs contributes to its pathogenesis. We aimed to reveal the expression profiles of RNAs, including messenger RNA (mRNA), circular RNA (circRNA) and long non-coding RNA (lncRNA), in the peripheral blood mononuclear cells (PBMCs) of patients with NMOSD. Seven NMOSD patients and seven healthy controls (HCs) were enrolled in the competitive endogenous RNA (ceRNA) microarray analysis. Bioinformatics analysis was then performed on the microarray data. Selected RNAs were validated by RT-qPCR. Differentially expressed (DE) RNA profiles of patients and HCs were related to NK cell mediated cytotoxicity, the IL-17 signaling pathway, and the B cell receptor signaling pathway. Moreover, DE non-coding RNAs (DE ncRNAs) including DE circRNAs and DE lncRNAs, may participate in the transforming growth factor beta (TGF-ß) signaling pathway, leukocyte migration and neutrophil chemotaxis. Immune cell infiltration analysis showed that the abundance of M1 macrophages and plasma cells significantly increased, while that of M2 macrophages significantly decreased in the NMOSD group. Finally, through RT-qPCR validation, lnc-HELZ-7:1 (95% confidential interval of area under curve [95%CI of AUC] = 0.6633-1.0000), ring finger protein-LIM domain interacting (RLIM; 95%CI of AUC = 0.6980-1.0000), and hsa_circ_0026993 (95%CI of AUC = 0.7550-1.0000) could discriminate NMOSD from HCs by receiver operating characteristic curve analysis. To our knowledge, this is the first study to preliminarily investigate the RNA profiles, especially circRNA profiles in PBMCs of NMOSD patients from North China. We identified lnc-HELZ-7:1, RLIM, and hsa_circ_0026993 as the potential disease markers for NMOSD.

Liraglutide attenuate central nervous inflammation and demyelination through AMPK and pyroptosis-related NLRP3 pathway.

AIMS: Multiple sclerosis (MS) still maintains increasing prevalence and poor prognosis, while glucagon-like peptide-1 receptor (GLP-1R) agonists show excellent neuroprotective capacities recently. Thus, we aim to evaluate whether the GLP-1R agonist liraglutide (Lira) could ameliorate central nervous system demyelination and inflammation. METHODS: The therapeutic effect of Lira was tested on experimental autoimmune encephalitis (EAE) in vivo and a microglia cell line BV2 in vitro. RESULTS: Lira administration could ameliorate the disease score of EAE mice, delay the disease onset, ameliorate pathological demyelination and inflammation score in lumbar spinal cord, reduce pathogenic T helper cell transcription in spleen, restore phosphorylated adenosine monophosphate-activated protein kinase (pAMPK) level, autophagy level, and inhibit pyroptosis-related NLR family, pyrin domain-containing protein 3 (NLRP3) pathway in lumbar spinal cord. Additionally, cell viability test, lactate dehydrogenase release test, and dead/live cell staining test for BV2 cells showed Lira could not salvage BV2 from nigericin-induced pyroptosis significantly. CONCLUSION: Lira has anti-inflammation and anti-demyelination effect on EAE mice, and the protective effect of Lira in the EAE model may be related to regulation of pAMPK pathway, autophagy, and NLRP3 pathway. However, Lira treatment cannot significantly inhibit pyroptosis of BV2 cells in vitro. Our study provides Lira as a potential candidate for Multiple Sclerosis treatment.

BLK polymorphisms and expression level in neuromyelitis optica spectrum disorder.

AIM: This study aimed to determine the correlation between B-lymphoid tyrosine kinase (BLK) polymorphism, mRNA gene expression of BLK, and NMOSD in a Chinese Han population. BACKGROUND: B-lymphoid tyrosine kinase gene expressed mainly in B cells plays a key role in various autoimmune disorders. However, no studies have investigated the association of BLK polymorphisms with neuromyelitis optica spectrum disorder (NMOSD). METHODS: Han Chinese population of 310 subjects were recruited to analyze three single nucleotide polymorphisms (rs13277113, rs4840568, and rs2248932) under allele, genotype, and haplotype frequencies, followed by clinical characteristics stratified analysis. Real-time PCR was used to analyze mRNA expression levels of BLK in the peripheral blood mononuclear cells of 64 subjects. RESULTS: Patients with NMOSD showed lower frequencies of the minor allele G of rs2248932 than healthy controls (odds ratio (OR) =0.57, 95% confidence intervals (CI) 0.39-0.83, p = 0.003). The association between minor allele G of rs2248932 and reduced NMOSD susceptibility was found by applying genetic models of inheritance (codominant, dominant, and recessive) and haplotypes analysis. Subsequently, by stratification analysis for AQP4-positivity, the minor allele G frequencies of rs2248932 in AQP4-positive subgroup were significantly lower than in the healthy controls (OR =0.46, 95% CI 0.30-0.72, p = 0.001). Notably, the genotype GG of rs2248932 was more frequent in AQP4-negative subgroup (n = 14) than in AQP4-positive subgroup (n = 93) (p = 0.003, OR =0.05, 95% CI =0.01-0.57). BLK mRNA expression levels in the NMOSD patients (n = 36) were lower than in healthy controls (n = 28) (p < 0.05). However, the acute non-treatment (n = 7), who were untreated patients in the acute phase from the NMOSD group, showed BLK mRNA expression levels 1.8-fold higher than healthy controls (n = 8) (p < 0.05). CONCLUSION: This study evaluated that the minor allele G of rs2248932 in BLK is associated with reduced susceptibility to NMOSD and protected the risk of AQP4-positive. BLK mRNA expression in NMOSD was lower as compared to healthy controls while significantly increased in acute-untreated patients.

A multi-dosing regimen to enhance the spatial memory of normal rats with α5-containing GABAA receptor negative allosteric modulator L-655,708.

RATIONALE AND OBJECTIVES: The reported inconsistent effects of negative allosteric modulators of α5-containing GABAA receptors on learning and memory may be attributed to receptor selectivity, effective plasma concentration maintenance, and administration time. This study aimed to compare the effects of L-655,708 administered by single-dosing regimen versus multi-dosing regimen on spatial memory, signaling molecules, and brain functional connectivity. METHODS: After comparing the maintenance time of the effective plasma concentration of L-655,708 between multi-dosing and single-dosing regimens, we further compared the effects of the administration of the two regimens at different phases (before-learning, during-learning, and before-probe) of the Morris water maze (MWM) test on the performance of learning and memory and the levels of signaling molecules related to learning and memory in hippocampal tissues. Functional connectivity analyses between hippocampal and cortical regions were performed to further clarify the effects of the multi-dosing regimen. RESULTS: The multi-dosing regimen could maintain the effective plasma concentration of L-655,708 much longer than the single-dosing regimen. Only the multi-dosing regimen for L-655,708 administration during the learning period led to significant improvement in spatial memory in the MWM test and increases in levels of glutamate receptors and phosphorylated signaling molecules (p-PKAα, p-CaMKII, and p-CREB-1). Compared with the vehicle control, the multi-dosing regimen increased the functional connectivity of the left hippocampal CA1 with cingulate and motor cortices. CONCLUSIONS: A multi-dosing regimen for L-655,708 administered during the learning period is an effective strategy to improve spatial memory, increase signaling molecule levels, and enhance the functional connectivity of the hippocampus.

PD-L1 Regulates Inflammation in LPS-Induced Lung Epithelial Cells and Vascular Endothelial Cells by Interacting with the HIF-1α Signaling Pathway.

Sepsis-induced lung injury was the most common cause of death in patients. This study aimed to investigate whether PD-L1 regulates the inflammation in LPS-induced lung epithelial cells and vascular endothelial cells by interacting with the HIF-1α signaling pathway. Sepsis-induced lung injury mice were constructed by cecal ligation and puncture (CLP) procedure, and lipopolysaccharide (LPS)-induced lung epithelial cells and vascular endothelial cells simulate the sepsis-induced lung injury model in vitro. Hematoxylin-eosin (HE) staining detected the morphological changes of the lung tissues, and immunohistochemistry (IHC) detected the PD-L1 expression in lung tissues. Bicinchoninic acid (BCA) assay determined the protein concentration in bronchial alveolar lavage fluid (BALF). The number of PD-1 (+) cells in blood was detected by flow cytometry. The apoptosis in lung tissues and LPS-induced cells was analyzed by TUNEL assay. The inflammatory factor levels and HIF-1α in lung tissues and LPS-induced cells were analyzed by ELISA. The transfection effects of KD-PDL1 or KD-HIF1A in lung epithelial cells and vascular endothelial cells were confirmed by qRT-PCR analysis. The protein expression related to the PD-L1- and HIF-1α-related pathway was determined by Western blot analysis. As a result, LMT-28, as an IL-6 inhibitor, alleviated lung injury and suppressed the apoptosis and inflammation in lung tissues in BALF and the number of PD-1 (+) cells in blood. Sepsis-induced lung injury activated the PD-L1- and HIF-1α-related pathway, while LMT-28 could not completely inhibit the pathway. In addition, downregulation of PD-L1 or downregulation of HIF-1α suppressed the apoptosis and alleviated the inflammation in LPS-induced lung epithelial cells and vascular endothelial cells. Downregulation of PD-L1 had significant effects on lung epithelial cells but had greater effects on vascular endothelial cells. Downregulation of HIF-1α could decrease PD-L1 expression, and downregulation of PD-L1 could also suppress the protein expression of HIF-1α and related pathways. In conclusion, downregulation of PD-L1 alleviated the inflammation in LPS-induced lung epithelial cells and vascular endothelial cells by suppressing the HIF-1α signaling pathway.

Real-time determination of earthquake focal mechanism via deep learning.

An immediate report of the source focal mechanism with full automation after a destructive earthquake is crucial for timely characterizing the faulting geometry, evaluating the stress perturbation, and assessing the aftershock patterns. Advanced technologies such as Artificial Intelligence (AI) has been introduced to solve various problems in real-time seismology, but the real-time source focal mechanism is still a challenge. Here we propose a novel deep learning method namely Focal Mechanism Network (FMNet) to address this problem. The FMNet trained with 787,320 synthetic samples successfully estimates the focal mechanisms of four 2019 Ridgecrest earthquakes with magnitude larger than Mw 5.4. The network learns the global waveform characteristics from theoretical data, thereby allowing the extensive applications of the proposed method to regions of potential seismic hazards with or without historical earthquake data. After receiving data, the network takes less than two hundred milliseconds for predicting the source focal mechanism reliably on a single CPU.

Locating induced earthquakes with a network of seismic stations in Oklahoma via a deep learning method.

The accurate and automated determination of small earthquake (ML < 3.0) locations is still a challenging endeavor due to low signal-to-noise ratio in data. However, such information is critical for monitoring seismic activity and assessing potential hazards. In particular, earthquakes caused by industrial injection have become a public concern, and regulators need a solid capability for estimating small earthquakes that may trigger the action requirements for operators to follow in real time. In this study, we develop a fully convolutional network and locate earthquakes induced during oil and gas operations in Oklahoma with data from 30 network stations. The network is trained by 1,013 cataloged events (ML ≥ 3.0) as base data along with augmented data accounting for smaller events (3.0 > ML ≥ 0.5), and the output is a 3D volume of the event location probability in the Earth. The prediction results suggest that the mean epicenter errors of the testing events (ML ≥ 1.5) vary from 3.7 to 6.4 km, meeting the need of the traffic light system in Oklahoma, but smaller events (ML = 1.0, 0.5) show errors larger than 11 km. Synthetic tests suggest that the accuracy of ground truth from catalog affects the prediction results. Correct ground truth leads to a mean epicenter error of 2.0 km in predictions, but adding a mean location error of 6.3 km to ground truth causes a mean epicenter error of 4.9 km. The automated system is able to distinguish certain interfered events or events out of the monitoring zone based on the output probability estimate. It requires approximately one hundredth of a second to locate an event without the need for any velocity model or human interference.

Role of Elastography in Axillary Examination of Patients With Breast Cancer.

OBJECTIVES: This study aimed at exploring the role of ultrasound (US) elastography in the diagnosis of the axillary lymph node status in patients with breast cancer. METHODS: We analyzed 140 visible axillary lymph nodes on conventional US imaging. All of them underwent elastography. Five conventional US features were adopted to assess axillary lymph nodes: longitudinal diameter, longitudinal-to-transverse diameter ratio, cortical thickness, status of the hilum, and vascular pattern. As for elastography, the proportion of the hard area within each lymph node was estimated visually. The lymph node was defined as positive on elastography when the proportion was 50% or greater. Meanwhile, disjunctive and conjunctive combinations of US and elastography were adopted to evaluate the lymph nodes. The histopathologic diagnosis was regarded as the reference standard. RESULTS: The sensitivity, specificity, and accuracy were 76.92%, 87.10%, and 81.43%, respectively, for conventional US and 84.62%, 83.87%, and 84.29% for the disjunctive combination. The conjunctive combination had specificity of 100% and a positive predictive value of 100%, whereas the sensitivity was low. CONCLUSIONS: Elastography can improve the sensitivity when disjunctively combined with conventional US for diagnosis of the axillary lymph node status. Despite the low sensitivity, the conjunctive combination of US and elastography can improve the positive predictive value on a large scale. Elastography is a useful adjuvant tool in addition to conventional US for the preoperative assessment of axillary lymph nodes in patients with breast cancer.

ZNF804A rs1344706 interacts with COMT rs4680 to affect prefrontal volume in healthy adults.

The biological function of ZNF804A rs1344706, the first genome-wide supported risk variant of schizophrenia, remains largely unknown. Based on the upregulating effect of ZNF804A on the expression of COMT, we hypothesize that ZNF804A may affect grey matter volume (GMV) by interacting with COMT. Voxel-based morphometry was applied to analyze the main and interaction effects of ZNF804A rs1344706 and COMT rs4680 on brain GMV in 274 healthy young human subjects. The GMV of the left dorsolateral prefrontal cortex (DLPFC) showed a significant COMT rs4680 × ZNF804A rs1344706 interaction, manifesting as an inverted U-shape modulation by the presumed dopamine signaling. In COMT Met-allele carriers, the ZNF804A TG heterozygotes showed greater GMV in the left DLPFC than both GG and TT homozygotes. In COMT Val/Val homozygotes, however, the ZNF804A TG heterozygotes exhibited smaller GMV in the left DLPFC than GG homozygotes and comparable GMV with TT homozygotes. These findings suggest that ZNF804A affects the GMV of the prefrontal cortex by interacting with COMT, which may improve our understanding of neurobiological effect of ZNF804A and its association with schizophrenia.