[Contamination levels of perfluorinated and polyfluoroalkyl compounds in breast milk and assessment of their exposure risk to infants].

The purposes of this study are to explore the contamination levels of perfluorinated and polyfluoroalkyl substances (PFASs) in breast milk and assess their exposure risk to infants. Based on data from a birth cohort study conducted in Yingcheng, Hubei Province, from 2018 to 2021, the contents of 23 types of PFASs in the breast milk of 324 pregnant women were determined using isotope dilution-high performance liquid chromatography-tandem mass spectrometry. Multiple linear regression was then performed to analyze the effects of various demographic characteristics and eating habits on the concentration of PFASs in breast milk. The daily PFASs intake of infants through breast milk was estimated, and the exposure risk of infants was also assessed. The results revealed that 23 types of PFASs in breast milk had good linear relationships in the range of 0.2-100 ng/mL, with correlation coefficients greater than 0.992. The limits of detection were 5-42 pg/mL, the limits of quantification were 15-126 pg/mL, the recoveries were 65.6%-108.1%, and the relative standard deviations were 1.6%-12.8%. Perfluorooctane sulfonic acid (PFOS), perfluorooctanoate acid (PFOA), and perfluorohexanesulfonic acid (PFHxS), with median concentrations of 200.7, 63.5, and 25.2 pg/mL, respectively, were the main PFASs found in breast milk. The detection rates of these three contaminants were higher than 80%, whereas the detection rates of other compounds were lower than 45%. The results of multiple linear regression showed that older pregnant women and a higher frequency of pickled food intake may be related to increased PFAS levels in breast milk whereas a higher frequency of legume intake may be related to decreased PFAS levels in breast milk. The median estimated daily intakes (EDIs) of PFOS, PFOA, and PFHxS for infants were 25.1, 7.9, and 3.2 ng/(kg·d), respectively. In summary, this study found notable PFAS levels in breast milk in Yingcheng, Hubei Province. Among these PFASs, PFOS, PFOA, and PFHxS were the main contaminants. Maternal age as well as pickled food and legume intake may affect the PFAS level in breast milk. The health risk of PFAS intake through breast milk to some infants is worthy of attention and further study.

Short-term effect of particulate matter on lung function and impulse oscillometry system (IOS) parameters of chronic obstructive pulmonary disease (COPD) in Beijing, China.

OBJECTIVE: This study aimed to evaluate the associations between particulate matter (PM), lung function and Impulse Oscillometry System (IOS) parameters in chronic obstructive pulmonary disease (COPD) patients and identity effects between different regions in Beijing, China. METHODS: In this retrospective study, we recruited 1348 outpatients who visited hospitals between January 2016 and December 2019. Ambient air pollutant data were obtained from the central monitoring stations nearest the participants' residential addresses. We analyzed the effect of particulate matter with aerodynamic diameter ≤ 2.5 µm (PM2.5) exposure on lung function and IOS parameters using a multiple linear regression model, adjusting for sex, smoking history, education level, age, body mass index (BMI), mean temperature, and relative humidity . RESULTS: The results showed a relationship between PM2.5, lung function and IOS parameters. An increase of 10 µg/m3 in PM2.5 was associated with a decline of 2.083% (95% CI: -3.047 to - 1.103) in forced expiratory volume in one second /predict (FEV1%pred), a decline of 193 ml/s (95% CI: -258 to - 43) in peak expiratory flow (PEF), a decline of 0.932% (95% CI: -1.518 to - 0.342) in maximal mid-expiratory flow (MMEF); an increase of 0.732 Hz (95% CI: 0.313 to 1.148) in resonant frequency (Fres), an increase of 36 kpa/(ml/s) (95% CI: 14 to 57) in impedance at 5 Hz (Z5) and an increase of 31 kpa/(ml/s) (95% CI: 2 to 54) in respiratory impedance at 5 Hz (R5). Compared to patients in the central district, those in the southern district had lower FEV1/FVC, FEV1%pred, PEF, FEF75%, MMEF, X5, and higher Fres, Z5 and R5 (p < 0.05). CONCLUSION: Short-term exposure to PM2.5 was associated with reductions in lung function indices and an increase in IOS results in patients with COPD. The heavier the PM2.5, the more severe of COPD.

A proteasomal ß5 subunit of Haemonchus contortus with a role in the growth, development and life span.

BACKGROUND: The proteasome in eukaryotic cells can degrade a variety of proteins and plays an important role in regulating the cell cycle, cell survival and apoptosis. The proteasome receives much attention as a potential chemotherapeutic target for treatment of a variety of infectious parasitic diseases, but few studies of proteasomes have been done on parasitic nematodes. METHODS: A proteasomal ß5 subunit encoding gene (named Hc-pbs-5) and its inferred product (Hc-PBS-5) in Haemonchus contortus were identified and characterized in this study. Then, the transcriptional profiles and anatomical expression were studied using an integrated molecular approach. Finally, a specific proteasome inhibitor bortezomib (BTZ), together with RNA interference (RNAi), was employed to assess the function of Hc-PBS-5. RESULTS: Bioinformatic analysis revealed that the coding sequence of Hc-pbs-5 was 855 bp long and encoded 284 amino acids (aa). The predicted protein (Hc-PBS-5) had core conservative sequences (65-250 aa) belonging to N-terminal nucleophile (Ntn) family of hydrolases. Real-time PCR results revealed that Hc-pbs-5 was continuously transcribed in eight developmental stages with higher levels at the infective third-stage larvae (L3s) and adult males of H. contortus. Immunohistochemical results revealed that Hc-PBS-5 was expressed in intestine, outer cuticle, muscle cells under the outer cuticle, cervical glands and seminal vesicles of male adults and also in intestine, outer cuticle, cervical glands, uterine wall, eggs and ovaries of female adults of H. contortus. BTZ could reduce proportions of egg hatching, and the fourth-stage larvae (L4s) developed from the exsheathed L3s (xL3s) of H. contortus. In addition, silencing Hc-pbs-5 by soaking the specific double-stranded RNA (dsRNA) could decrease the transcription of Hc-pbs-5 and result in fewer xL3s developing to L4s in vitro. CONCLUSIONS: These results indicate that proteasomal ß5 subunit plays an important role in the growth, development and life span of H. contortus.

Cooperative Particle Swarm Optimization With a Bilevel Resource Allocation Mechanism for Large-Scale Dynamic Optimization.

Although cooperative coevolutionary algorithms are developed for large-scale dynamic optimization via subspace decomposition, they still face difficulties in reacting to environmental changes, in the presence of multiple peaks in the fitness functions and unevenness of subproblems. The resource allocation mechanisms among subproblems in the existing algorithms rely mainly on the fitness improvements already made but not potential ones. On the one hand, there is a lack of sufficient computing resources to achieve potential fitness improvements for some hard subproblems. On the other hand, the existing algorithms waste computing resources aiming to find most of the local optima of problems. In this article, we propose a cooperative particle swarm optimization algorithm to address these issues by introducing a bilevel balanceable resource allocation mechanism. A search strategy in the lower level is introduced to select some promising solutions from an archive based on solution diversity and quality to identify new peaks in every subproblem. A resource allocation strategy in the upper level is introduced to balance the coevolution of multiple subproblems by referring to their historical improvements and more computing resources are allocated for solving the subproblems that perform poorly but are expected to make great fitness improvements. Experimental results demonstrate that the proposed algorithm is competitive with the state-of-the-art algorithms in terms of objective function values and response efficiency with respect to environmental changes.

[Psittacosis Pneumonia with Pleural Effusion:Report of Three Cases and Literature Review].

It was generally believed that psittacosis pneumonia (pneumonia caused by Chlamydia psittaci) was rarely combined with pleural effusion and the characteristics of pleural effusion were rarely reported in the domestic literature.Herein,we reported three cases of pleural effusion due to psittacosis pneumonia,with elevated level of adenosine deaminase and lymphocyte-predominant exudative pleural effusion.Further,we reviewed the psittacosis pneumonia reports with complete clinical and lung imaging data.The imaging manifestations included pulmonary consolidation and common occurrence of a small amount of pleural effusion.The patients of psittacosis pneumonia combined with pleural effusion had severe symptoms,obvious hypoxia,and increased risk of invasive ventilation.

Nematicidal activity of volatile organic compounds produced by Bacillus altitudinis AMCC 1040 against Meloidogyne incognita.

The application of nematicidal microorganisms and their virulence factors provides more opportunities to control root-knot nematodes. Bacillus altitudinis AMCC 1040, previously isolated from suppressive soils, showed significant nematicidal activity, and in this study, nematicidal substances produced by Bacillus altitudinis AMCC 1040 were investigated. The results of the basic properties of active substances showed that these compounds have good thermal stability and passage, are resistant to acidic environment and sensitive to alkaline conditions. Further analysis showed that it is a volatile component. Using HS-SPME-GC/MS, the volatile compounds produced by Bacillus altitudinis AMCC 1040 were identified and grouped into four major categories: ethers, alcohols, ketone, and organic acids, comprising a total of eight molecules. Six of them possess nematicidal activities, including 2,3-butanedione, acetic acid, 2-isopropoxy ethylamine, 3-methylbutyric acid, 2-methylbutyric acid and octanoic acid. Our results further our understanding of the effects of Bacillus altitudinis and its nematicidal metabolites on the management of Meloidogyne incognita and may help in finding less toxic nematicides to control root knot nematodes.

The correlation of EZH2 expression with the progression and prognosis of hepatocellular carcinoma.

BACKGROUND: Enhancer of Zeste homologue 2 (EZH2) is a polycomb group gene and an epigenetic regulator that inhibits transcription, a modification associated with gene silencing. EZH2 plays an essential role in humoral and cell-mediated adaptive immunity. The purpose of the current study is to investigate the prognostic potential of EZH2 and to comprehensively analyse the correlation between EZH2 and immune infiltration in multiple cancer cases, especially liver hepatocellular carcinoma. METHODS: EZH2 expression across cancers was explored through Oncomine, HPA, and GEPIA2. Additionally, the prognostic value of EZH2 analysis across cancers was based on the GEPIA2, TCGA portal, Kaplan-Meier Plotter, and LOGpc databases. Based on GO and KEGG analyses, GSEA helped demonstrate the biological processes through which EZH2 might lead to HCC development. GEPIA and TIMER were adopted to detect the possible relationship of EZH2 expression with tumour-infiltrating immune cells (TIICs). RESULTS: EZH2 overexpression levels were associated with poor prognosis of cancer, especially hepatocellular carcinoma. A high EZH2 expression level is related to a poor prognosis of HCC, especially in disease histology and stage III. The EZH2 expression level was positively correlated with critical gene markers of TAMs, M2 macrophages, M1 macrophages, and monocytes. Further analysis revealed that EZH2 genes were mainly related to DNA recombination, mitotic cell cycle phase transition, and chromosome segregation. CONCLUSION: EZH2 plays an essential role in the immune microenvironment and is a potential prognostic marker and immunotherapy target for hepatocellular carcinoma.

New-onset COVID-19-related diabetes: an early indicator of multi-organ injury and mortally of SARS-CoV-2 infection.

Objective: The pandemic of 2019 coronavirus (SARS-CoV-2) disease (COVID-19) has imposed a severe public health burden worldwide. Most patients with COVID-19 were mild. Severe patients progressed rapidly to critical condition including acute respiratory distress syndrome (ARDS), multi-organ failure and even death. This study aims to find early multi-organ injury indicators and blood glucose for predicting mortality of COVID-19. Methods: Fasting blood glucose (FBG) ≥7.0 mmol/L for two times during hospitalization and without a history of diabetes were defined as new-onset COVID-19-related diabetes (CRD). Indicators of injuries for multiple organs, including the lung, heart, kidney and liver, and glucose homeostasis were specifically analyzed for predicting death. Results: A total of 120 patients with a severity equal to or greater than Moderate were hospitalized. After excluding patients with history of diabetes, chronic heart, kidney, and liver disease, 69 patients were included in the final analysis. Of the 69 patients, 23 were Moderate, 20 were Severe, and 26 were Critical (including 16 deceased patients). Univariable analysis indicated that CRD, lactate dehydrogenase (LDH), hydroxybutyrate dehydrogenase (HBDH), creatine kinase (CK) and creatinine (Cr) were associated with death. Multivariable analysis indicated that CRD was an independent predictor for death (HR = 3.75, 95% CI 1.26-11.15). Abnormal glucose homeostasis or CRD occurred earlier than other indicators for predicting poor outcomes. Indicators of multiple organ injury were in parallel with the expression patterns of ACE2 (the SARS-CoV-2 receptor) in different organs including pancreatic islet. Conclusions: New-onset COVID-19-related diabetes is an early indicator of multi-organ injury and predictor for poor outcomes and death in COVID-19 patients. As it is easy to perform for clinical practices and self-monitoring, glucose testing will be helpful for predicting poor outcomes to facilitate appropriate intensive care.

Activation and Characterization of Lanthomicins A-C by Promoter Engineering in Streptomyces chattanoogensis L10.

The emergence of drug resistance highlights the importance of new drug discovery. Microbial secondary metabolites encoded in biosynthetic gene clusters (BGCs) are a prolific source of drugs, whereas most of these BGCs are cryptic. Thus, taking strategies to activate these cryptic BGCs is of great importance for potential drug discovery. In this work, three novel pentangular polyphenols lanthomicin A-C were identified by activating a cryptic aromatic polyketide BGC through promoter engineering combined with optimization of fermentation conditions. We further confirmed the involvement of lanthomicin (ltm) BGC in biosynthesis by CRISPR-Cpf1-assisted gene editing. Based on functional analysis of homologous genes, a putative biosynthetic pathway was proposed for the three lanthomicins. Particularly, lanthomicin A showed antiproliferative activity with IC50 0.17 µM for lung cancer cell line A-549. The discovery of lanthomicins brings new members to the pentangular polyphenol subclade of aromatic polyketide and demonstrates the potential of Streptomyces as a source for drug discovery.

Directed Evolution of a Nonheme Diiron N-oxygenase AzoC for Improving Its Catalytic Efficiency toward Nitrogen Heterocycle Substrates.

The azoxy compounds with an intriguing chemical bond [-N=N+(-O-)-] are known to have broad applications in many industries. Our previous work revealed that a nonheme diiron N-oxygenase AzoC catalyzed the oxidization of amino-group to its nitroso analogue in the formation of azoxy bond in azoxymycins biosynthesis. However, except for the reported pyridine alkaloid azoxy compounds, most azoxy bonds of nitrogen heterocycles have not been biosynthesized so far, and the substrate scope of AzoC is limited to p-aminobenzene-type compounds. Therefore, it is very meaningful to use AzoC to realize the biosynthesis of azoxy nitrogen heterocycles compounds. In this work, we further studied the catalytic potential of AzoC toward nitrogen heterocycle substrates including 5-aminopyrimidine and 5-aminopyridine compounds to form new azoxy compounds through directed evolution. We constructed a double mutant L101I/Q104R via molecular engineering with improved catalytic efficiency toward 2-methoxypyrimidin-5-amine. These mutations also proved to be beneficial for N-oxygenation of methyl 5-aminopyrimidine-2-carboxylate. The structural analysis showed that relatively shorter distance between the substrate and the diiron center and amino acid residues of the active center may be responsible for the improvement of catalytic efficiency in L101I/Q104R. Our results provide a molecular basis for broadening the AzoC catalytic activity and its application in the biosynthesis of azoxy six-membered nitrogen catenation compounds.

Resource-Aware Distributed Differential Evolution for Training Expensive Neural-Network-Based Controller in Power Electronic Circuit.

The neural-network (NN)-based control method is a new emerging promising technique for controller design in a power electronic circuit (PEC). However, the optimization of NN-based controllers (NNCs) has significant challenges in two aspects. The first challenge is that the search space of the NNC optimization problem is such complex that the global optimization ability of the existing algorithms still needs to be improved. The second challenge is that the training process of the NNC parameters is very computationally expensive and requires a long execution time. Thus, in this article, we develop a powerful evolutionary computation-based algorithm to find a high-quality solution and reduce computational time. First, the differential evolution (DE) algorithm is adopted because it is a powerful global optimizer in solving a complex optimization problem. This can help to overcome the premature convergence in local optima to train the NNC parameters well. Second, to reduce the computational time, the DE is extended to distribute DE (DDE) by dispatching all the individuals to different distributed computing resources for parallel computing. Moreover, a resource-aware strategy (RAS) is designed to further efficiently utilize the resources by adaptively dispatching individuals to resources according to the real-time performance of the resources, which can simultaneously concern the computing ability and load state of each resource. Experimental results show that, compared with some other typical evolutionary algorithms, the proposed algorithm can get significantly better solutions within a shorter computational time.

The anti-neoplastic activities of aloperine in HeLa cervical cancer cells are associated with inhibition of the IL-6-JAK1-STAT3 feedback loop.

Cervical cancer (CC) is recognized as the most common neoplasm in the female reproductive system worldwide. The lack of chemotherapeutic agents with outstanding effectiveness and safety severely compromises the anti-cipated prognosis of patients. Aloperine (ALO) is a natural quinolizidine alkaloid with marked anti-cancer effects on multiple malignancies as well as favorable activity in relieving inflammation, allergies and infection. However, its therapeutic efficacy and underlying mechanism in CC are still unclear. In the current study, MTT assay was employed to evaluate the viability of HeLa cells exposed to ALO to preliminarily estimate the effectiveness of ALO in CC. Then, the effects of ALO on the proliferation and apoptosis of HeLa cells were further investigated by plate colony formation and flow cytometry, respectively, while the migration and invasion of ALO-treated HeLa cells were evaluated using Transwell assay. Moreover, nude mice were subcutaneously inoculated with HeLa cells to demonstrate the anti-CC properties of ALO in vivo. The molecular mechanisms underlying these effects of ALO were evaluated by Western blot and immunohistochemical analysis. This study experimentally demonstrated that ALO inhibited the proliferation of HeLa cells via G2 phase cell cycle arrest. Simultaneously, ALO promoted an increase in the percentage of apoptotic HeLa cells by increasing the Bax/Bcl-2 ratio. Additionally, the migration and invasion of HeLa cells were attenuated by ALO treatment, which was considered to result from inhibition of epithelial-to-mesenchymal transition. For molecular mechanisms, the expression and activation of the IL-6-JAK1-STAT3 feedback loop were markedly suppressed by ALO treatment. This study indicated that ALO markedly suppresses the proliferation, migration and invasion and enhances the apoptosis of HeLa cells. In addition, these prominent anti-CC properties of ALO are associated with repression of the IL-6-JAK1-STAT3 feedback loop.

KCTD11 inhibits progression of lung cancer by binding to ß-catenin to regulate the activity of the Wnt and Hippo pathways.

KCTD11 has been reported to be a potential tumour suppressor in several tumour types. However, the expression of KCTD11 and its role has not been reported in human non-small cell lung cancer (NSCLC). Whether its potential molecular mechanism is related to its BTB domain is also unknown. The expression of KCTD11 in 139 NSCLC tissue samples was detected by immunohistochemistry, and its correlation with clinicopathological factors was analysed. The effect of KCTD11 on the biological behaviour of lung cancer cells was verified in vitro and in vivo. Its effect on the epithelial-mesenchymal transition(EMT)process and the Wnt/ß-catenin and Hippo/YAP pathways were observed by Western blot, dual-luciferase assay, RT-qPCR, immunofluorescence and immunoprecipitation. KCTD11 is under-expressed in lung cancer tissues and cells and was negatively correlated with the degree of differentiation, tumour-node-metastasis (TNM) stage and lymph node metastasis. Low KCTD11 expression was associated with poor prognosis. KCTD11 overexpression inhibited the proliferation and migration of lung cancer cells. Further studies indicated that KCTD11 inhibited the Wnt pathway, activated the Hippo pathway and inhibited EMT processes by inhibiting the nuclear translocation of ß-catenin and YAP. KCTD11 lost its stimulatory effect on the Hippo pathway after knock down of ß-catenin. These findings confirm that KCTD11 inhibits ß-catenin and YAP nuclear translocation as well as the malignant phenotype of lung cancer cells by interacting with ß-catenin. This provides an important experimental basis for the interaction between KCTD11, ß-catenin and YAP, further revealing the link between the Wnt and Hippo pathways.

Ultrasound-guided thermal ablation for papillary thyroid microcarcinoma: a multicenter retrospective study.

PURPOSE: Ultrasound-guided thermal ablation (including microwave ablation [MWA] and radiofrequency ablation [RFA]) has emerged as a remarkable technology for the treatment of benign and malignant diseases. The objective of this multicenter study was to assess the efficacy and safety of thermal ablation in a large cohort of patients with papillary thyroid microcarcinoma (PTMC). MATERIALS AND METHODS: Retrospective study of 725 patients who underwent MWA/RFA at 11 centers between March 2015 and March 2020. The mean age of patients was 46 ± 11 years (range, 22-81); the mean follow-up time was 21 ± 13 months (range, 6-60). Changes in size of tumor, the rates of tumor disappearance, disease progression, and complications were assessed. RESULTS: From 6 months post-ablation, the size of tumors was significantly reduced compared with those recorded pre-ablation (p < 0.001 for all). Five hundred and fifteen (71.0%) PTMCs had completely disappeared as assessed by ultrasound examination. Six (0.8%) patients developed disease progression post-ablation; of these, 5 (0.7%) patients developed new PTMCs, while one (0.1%) patient developed cervical lymph node metastasis. Nineteen (2.6%) patients developed complications post-ablation; of these 14 (1.9%) patients developed voice hoarseness, 4 (0.6%) developed hematoma, and one (0.1%) patient developed cough. CONCLUSIONS: Ultrasound-guided thermal ablation represents an effective and safe treatment for patients with PTMC besides active surveillance and surgery.

Docosahexaenoic acid-enriched phospholipids and eicosapentaenoic acid-enriched phospholipids inhibit tumor necrosis factor-alpha-induced lipolysis in 3T3-L1 adipocytes by activating sirtuin 1 pathways.

Some chronic diseases such as cancer-associated cachexia (CAC) and obesity are associated with the overproduction of tumor necrosis factor-alpha (TNF-α) that stimulates excess lipolysis in adipocytes. Our previous studies have shown that docosahexaenoic acid-enriched phospholipids (DHA-PL) and eicosapentaenoic acid-enriched phospholipids (EPA-PL) ameliorated CAC and obesity-related metabolic disorders. To identify the molecular mechanisms involved, we examined the impact and the associated signaling pathways of DHA-PL and EPA-PL on TNF-α-induced lipolysis in 3T3-L1 adipocytes. The present results revealed that DHA-PL and EPA-PL inhibited the TNF-α-induced increase of glycerol release and protected lipid droplets. In addition, DHA-PL and EPA-PL increased DHA and EPA contents in the phospholipid fraction of adipocytes, respectively. Moreover, DHA-PL and EPA-PL enhanced sirtuin 1 (SIRT1) deacetylase activity and its protein expression. By activating SIRT1, DHA-PL and EPA-PL upregulated the G0/G1 switch gene 2 protein level to inhibit adipose triglyceride lipase activity, activate AMP-activated protein kinase to reverse the downregulation of perilipin expression and phosphorylation of hormone-sensitive lipase (HSL) at Ser565 and prevent the phosphorylation of HSL at Ser660. Furthermore, DHA-PL and EPA-PL improved glucose uptake and glucose transporter type 4 translocation to the plasma membrane in TNF-α-treated adipocytes. Thus, it was concluded that DHA-PL and EPA-PL inhibit TNF-α-induced lipolysis in 3T3-L1 adipocytes by activating the SIRT1 pathways.

Efficacy and Safety of Thermal Ablation for Treatment of Solitary T1N0M0 Papillary Thyroid Carcinoma: A Multicenter Retrospective Study.

Background Microwave ablation (MWA) and radiofrequency ablation (RFA) have recently attracted interest as minimally invasive treatment modalities for papillary thyroid carcinoma (PTC). However, the ablation outcomes of T1N0M0 PTC are not well characterized. Purpose To evaluate the efficacy and safety of thermal ablation (MWA or RFA) of solitary T1N0M0 PTC in patients who were ineligible for (due to presence of comorbid cardiovascular disease, renal failure, other malignancy, etc) or who refused surgery. Materials and Methods This was a retrospective multicenter study of 847 patients (660 women) who underwent thermal ablation for PTC (673 T1a, 174 T1b) between March 2015 and March 2020; of these patients, 645 underwent MWA and 202 underwent RFA. The mean age of patients was 46 years ± 11 (standard deviation) (age range, 18-81 years); the mean follow-up time was 22 months ± 13 (range, 6-60 months). Changes in tumor size and volume and the rates of technical success, tumor disappearance, disease progression, and complications were assessed. Results The technical success rate was 100%. Relative to preablation measurements, the maximum diameter and volume of the ablation zone increased during the 1st month after ablation (P < .001), whereas there was no difference by the 3rd month; subsequently, the tumors showed reduction in size at 6, 9, and 12 months (all P < .001). Complete disappearance of tumors occurred in 68% of patients (577 of 847; 69% [466 of 673] in the T1a group vs 64% [111 of 174] in the T1b group; P < .001). The postablation disease progression rate was 1.1% (nine of 847 patients; 0.9% [six of 673 patients] in the T1a group vs 1.7% [three of 174 patients] in the T1b group; P = .54). The overall complication rate was 3.4% (29 of 847 patients; 2.7% [18 of 673 patients] in the T1a group vs 6.3% [11 of 174 patients] in the T1b group; P = .02). Conclusion This multicenter study provided evidence that thermal ablation is an effective and safe treatment option in selected -patients with solitary T1N0M0 papillary thyroid carcinoma. © RSNA, 2021 Online supplemental material is available for this article. See also the editorial by Baek and Cho in this issue.

Development and Validation of a Machine Learning Approach for Automated Severity Assessment of COVID-19 Based on Clinical and Imaging Data: Retrospective Study.

BACKGROUND: COVID-19 has overwhelmed health systems worldwide. It is important to identify severe cases as early as possible, such that resources can be mobilized and treatment can be escalated. OBJECTIVE: This study aims to develop a machine learning approach for automated severity assessment of COVID-19 based on clinical and imaging data. METHODS: Clinical data-including demographics, signs, symptoms, comorbidities, and blood test results-and chest computed tomography scans of 346 patients from 2 hospitals in the Hubei Province, China, were used to develop machine learning models for automated severity assessment in diagnosed COVID-19 cases. We compared the predictive power of the clinical and imaging data from multiple machine learning models and further explored the use of four oversampling methods to address the imbalanced classification issue. Features with the highest predictive power were identified using the Shapley Additive Explanations framework. RESULTS: Imaging features had the strongest impact on the model output, while a combination of clinical and imaging features yielded the best performance overall. The identified predictive features were consistent with those reported previously. Although oversampling yielded mixed results, it achieved the best model performance in our study. Logistic regression models differentiating between mild and severe cases achieved the best performance for clinical features (area under the curve [AUC] 0.848; sensitivity 0.455; specificity 0.906), imaging features (AUC 0.926; sensitivity 0.818; specificity 0.901), and a combination of clinical and imaging features (AUC 0.950; sensitivity 0.764; specificity 0.919). The synthetic minority oversampling method further improved the performance of the model using combined features (AUC 0.960; sensitivity 0.845; specificity 0.929). CONCLUSIONS: Clinical and imaging features can be used for automated severity assessment of COVID-19 and can potentially help triage patients with COVID-19 and prioritize care delivery to those at a higher risk of severe disease.

Prognostic significance of KIF23 expression in gastric cancer.

BACKGROUND: Kinesin super family 23 (KIF23) is a member of the KIF family, and it plays an important role in mitosis and cytokinesis. Loss of expression can cause mitotic arrest. The Oncomine database is one of the largest oncogene chip databases in the world, and is an integrated data mining platform for cancer gene information. By querying the database, differences in expression between tumor tissue and normal tissue can be determined. AIM: To study the expression and prognostic significance of KIF23 in gastric cancer (GC). METHODS: We used immunohistochemistry to compare the expression of KIF23 in GC and normal gastric tissues. We mined the data on the expression and prognosis of KIF23 in GC using Oncomine and Kaplan-Meier plotter database. RESULTS: Compared with normal gastric tissues, KIF23 expression was increased in GC tissues, and correlated with T, N, and tumor-node-metastasis stages. Survival analysis showed that patients with high expression of KIF23 had a poor overall survival. There were five studies in the Oncomine database in which expression of KIF23 was significantly higher in GC tissues than in normal gastric tissues (P < 0.05). Kaplan-Meier plotter database analysis showed that recurrence-free survival, overall survival, distant metastasis free survival, and post progression survival of patients with high expression of KIF23 were lower than those of patients with low expression. Further stratified analysis found that prognostic survival indicators worsened in patients with T2 and T3 poorly differentiated adenocarcinoma with high expression of KIF23. CONCLUSION: KIF23 is highly expressed in GC and is associated with a poor prognosis of patients. It may be of great significance in the diagnosis, treatment, and prognostic evaluation of GC.

Gender Differences in Patients With COVID-19: Focus on Severity and Mortality.

Objective: The recent outbreak of Novel Coronavirus Disease (COVID-19) is reminiscent of the SARS outbreak in 2003. We aim to compare the severity and mortality between male and female patients with COVID-19 or SARS. Study Design and Setting: We extracted the data from: (1) a case series of 43 hospitalized patients we treated, (2) a public data set of the first 37 cases of patients who died of COVID-19 and 1,019 patients who survived in China, and (3) data of 524 patients with SARS, including 139 deaths, from Beijing in early 2003. Results: Older age and a high number of comorbidities were associated with higher severity and mortality in patients with both COVID-19 and SARS. Age was comparable between men and women in all data sets. In the case series, however, men's cases tended to be more serious than women's (P = 0.035). In the public data set, the number of men who died from COVID-19 is 2.4 times that of women (70.3 vs. 29.7%, P = 0.016). In SARS patients, the gender role in mortality was also observed. The percentage of males were higher in the deceased group than in the survived group (P = 0.015). Conclusion: While men and women have the same prevalence, men with COVID-19 are more at risk for worse outcomes and death, independent of age.

ANKHD1 promotes proliferation and invasion of non­small­cell lung cancer cells via regulating YAP oncoprotein expression and inactivating the Hippo pathway.

The ankyrin repeat and KH domain­containing 1 (ANKHD1) protein was recently reported to be a potential member of the Hippo signaling pathway. However, its role in human non­small­cell lung cancer (NSCLC) has not been extensively investigated. The aim of the present study was to examine the expression of ANKHD1 in primary human tissues and cells and determine whether it is correlated with the clinical characteristics of tumor growth. The biological functions of ANKHD1 were evaluated in vitro and in vivo. Yes­associated protein (YAP) expression and phosphorylation induced by ANKHD1 were evaluated by western blotting and immunoprecipitation. Marked upregulation of ANKHD1 protein expression was observed in NSCLC cells and tissues, which was associated with advanced pathological tumor­node­metastasis stage, lymph node metastasis and poor prognosis in patients with NSCLC. ANKHD1 overexpression also promoted the proliferation and invasion of NSCLC cells. ANKHD1 upregulation inactivated Hippo signaling via increasing YAP protein levels, as well as inhibiting YAP protein phosphorylation, whereas depletion of YAP abolished the effects of ANKHD1 on cell proliferation and invasion. Therefore, ANKHD1 may play an important role in NSCLC through regulating the YAP­dependent Hippo signaling pathway.