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The rehabilitation of facial esthetics when transitioning from a failing dentition in a patient with maxillary protrusion is challenging. This clinical report described such a patient treated with an immediate cross-arch implant-supported fixed prosthesis. The ideal virtual upper lip position was used to predict the sagittal and vertical position of the restoration. A stackable device was fabricated to guide the osteotomy and implant placement.

This study investigates the contribution of Boreal Summer Intraseasonal Oscillation (BSISO) to the tropical cyclone (TC) activity over the North Indian Ocean (NIO) and assesses the prediction skill of a statistical Generalised Additive Model (GAM) and two machine learning techniques—Random Forest (RF) and Support Vector Regression (SVR). Joint Typhoon Warning Centre TC and BSISO1 Index data have been used for a period of 33-year (1981–2013). By considering eight phases of BSISO, prediction models have been developed using a kernel density estimation for the TC genesis, Euler integration step to fit the tracks, and a country mask approach for the landfall across the NIO rim countries. Result shows that GAM has the highest prediction skill compared to the RF and SVR. Westward and Northward moving TCs are controlled by the wind and the TC activities during BSISO phases which modulated by wind matched well against observations over the NIO. Distance calculation validation method is applied to assess the skill of models.

PURPOSE Inhibition of the MEK/ERK pathway is critical for Bcl-2-like protein 11 (BIM)-mediated epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI)-induced apoptosis, and dysregulation of this pathway may be a mechanism of acquired resistance. Therefore, MEK inhibition with trametinib and an EGFR TKI may resensitize tumors with acquired resistance. Limited targeted therapies are available after progression on EGFR TKIs, and it is in this setting that we completed a phase I/II study of erlotinib and trametinib. METHODS Patients with metastatic EGFR-mutant lung adenocarcinoma and acquired resistance to an EGFR TKI received combination erlotinib 75 mg and trametinib 1.5 mg daily until progression or unacceptable side effects. The primary objective was objective response rate determined using RECIST version 1.1. RESULTS Twenty-three patients were accrued; patients had received a median of two lines of prior TKI therapy (61% prior osimertinib), and 48% had acquired EGFR T790M. We confirmed one partial response (1/23, 4%, 95% CI, 0 to 22). The median progression-free survival was 1.8 months, and the median overall survival was 21 months. Diarrhea (87%), acneiform rash (87%), and fatigue (52%) were the most common treatment-related adverse events. Two patients who had tumor shrinkage both harbored a BRAF fusion. CONCLUSION Addition of trametinib to erlotinib in the acquired resistance setting in an unselected population is not efficacious. Future studies should focus on targeted therapies in molecularly selected populations. Acquired BRAF fusions in patients with EGFR-sensitizing mutations may be a molecular subset where EGFR and MEK combination therapy could be studied further.

BACKGROUND Malignant adenomyoepithelioma (AME) of the breast is a rare tumor in which malignancy can arise from either epithelial or myoepithelial components, or from both cell types. The incidence and prognosis of malignant AME of the breast are difficult to assess due to its rarity. Therefore, the optimal treatment for this disease is still controversial. CASE SUMMARY We present two middle-aged women (48 and 56 years old) with malignant AME of the breast. Core needle biopsy was performed before surgery. However, breast adenoma and malignant tumors were observed. The preoperative diagnosis of malignant AME of the breast is still challenging for pathologists and clinicians. Both patients underwent mastectomy and sentinel lymph node biopsy, both of which were negative, followed by adjuvant chemotherapy. CONCLUSION The follow-up duration of the two patients was two years and four months, respectively. No signs of relapse or metastasis have been observed thus far.

We explore how managers with foreign experience affect corporate fraud in China. By employing a bivariate probit model with partial observability, we find that returnee managers significantly reduc...

Yuchen Zhong,1,2 Tianyi Ma,1 Tianyu Qiao,1 Hanqing Hu,1 Zhengliang Li,1 Kangjia Luo,1 Yuliuming Wang,1 Qingchao Tang,1 Guiyu Wang,1,2 Rui Huang,1 Xishan Wang3 1Department of Colorectal Surgery, The Second Affiliated Hospital of Harbin Medical University, Harbin, Heilongjiang, 150080, People’s Republic of China; 2Department of Colorectal Surgery, The Cancer Hospital of the University of Chinese Academy of Sciences (Zhejiang Cancer Hospital), Hangzhou, Zhejiang, 310002, People’s Republic of China; 3Department of Colorectal Surgery, National Cancer Center/Cancer Hospital, Chinese Academy of Medical Science and Peking Union Medical College, National Clinical Research Center for Cancer, Beijing, 100021, People’s Republic of ChinaCorrespondence: Guiyu Wang; Rui HuangDepartment of Colorectal Surgery, The Second Affiliated Hospital of Harbin Medical University, Harbin, Heilongjiang, 150080, People’s Republic of ChinaTel/Fax +86-19558225177; +86-15204620800Email guiyWang@163.com; huangrui2019@163.comObjective: To investigate the relationship between circulating tumor cells (CTCs) and their subpopulations and colorectal cancer (CRC). To explore the application of CTCs’ numbers and positive rates in the diagnosis and treatment of CRC, and to assess the effect of surgery on CTCs numbers and positivity.Methods: We identified CTCs using the CanPatrol technique after enrollment. Peripheral blood samples were collected from 74 CRC patients before anti-tumor treatment. CTCs can be divided into the following three phenotypes: epithelial CTCs (E-CTCs) (EpCAM+, Vimentin-), mesenchymal CTCs (M-CTCs) (EpCAM-, Vimentin+), and mixed CTCs (E/M-CTCs) (EpCAM+, Vimentin+). CTCs and the proportion of subtypes were statistically compared with clinicopathological characteristics.Results: The positive rate of M-CTCs was significantly higher in patients with tumor size ≥ 5 cm (85.7% vs 49.1%, P = 0.004) and carcinoembryonic antigen (CEA) > 5 ng/mL (83.3% vs 51.0% p = 0.024). Moreover, the T stage (T1 0, T2 33.3%, T3 59.4%, T4 100%, p < 0.0005) and TNM stage (stage I 11.8%, stage II 79.2%, stage III 64.3%, stage IV 100%, p < 0.0005) were correlated with the positive rate of M-CTCs. We also found that the proportion of M-CTCs was correlated with the T stage (p < 0.0005) and TNM stage (p=0.0200), but not with the N stage (p=0.6889). In survival analysis, M-CTCs > 1 were found associated with worse disease-free survival (p=0.007). After treatment, the number and proportion of CTCs and M-CTCs were significantly reduced.Conclusion: The positive rate of M-CTCs was associated with tumor size, T stage, TNM stage, vascular invasion, and CEA. As the disease progressed, the proportion of M-CTCs gradually increased, and the survival performance was worse in patients with a high positive rate of M-CTCs.Keywords: circulating tumor cells, colorectal cancer, surgery, EMT

Background With the emergence of three-dimensional (3D) integration technology, analysis of soft tissue displacement and morphological changes after maxillary full-arch implant-supported fixed prostheses can be performed. The aim of this study was to verify the feasibility of the 3D integration method for constructing the relative position of the prostheses and facial soft tissue, evaluate the displacement and morphological variation of the upper lips after maxillary full-arch implant-supported fixed prostheses. Methods Twenty-five maxillary edentulous patients were recruited in this study. At the time of final prosthesis delivery, the 3D prostheses data and three 3D facial profiles were integrated. After method validation, the 3D position changes of seven soft tissue landmarks were used to reflect the 25 upper lips. The variation of four morphological distances were analyzed to reflect the morphological alteration of the upper lips. Two pairs of dentofacial landmarks were used to analyze the sagittal relative position of the prostheses and soft tissue. The included patients were also grouped to determine the impact of sex, upper lip thickness, and length on lip support changes. Results The average distance of the two matched relative reliable forehead regions was only 0.32 mm. The sagittal shifts of labrale superius (LS), stomion (STO), crista philtri left (CPHL) and crista philtri right (CPHR) were 3.44 ± 1.39 mm, 2.52 ± 1.38 mm, 3.04 ± 1.18 mm, and 3.12 ± 1.21 mm, respectively. With the exception of the decrease in the length of subnasale (SN)-LS, the length of cheilion right (CHR)-cheilion left (CHL), CPHR-CPHL, and LS-STO significantly increased. The two pairs of dentofacial landmarks had strong positive movement correlations along the sagittal direction. Patients with thinner and longer lips showed more lip support than those with thicker and shorter lips by a clinically insignificant amount. Conclusions The integration method of 3D facial and dental data showed high repeatability in constructing the dentofacial relative position. The linear equations reflecting dentofacial relative position could aid clinicians in evaluating the restoration effect and estimate the upper lip variation.

It’s a challenge for detecting the therapeutic targets of a polypharmacological drug from variations in the responsed networks in the differentiated populations with complex diseases, as stable coronary heart disease. Here, in an adaptive, 31-center, randomized, double-blind trial involving 920 patients with moderate symptomatic stable angina treated by 14-day Danhong injection(DHI), a kind of polypharmacological drug with high quality control, or placebo (0.9% saline), with 76-day following-up, we firstly confirmed that DHI could increase the proportion of patients with clinically significant changes on angina-frequency assessed by Seattle Angina Questionnaire (ΔSAQ-AF ≥ 20) (12.78% at Day 30, 95% confidence interval [CI] 5.86–19.71%, P = 0.0003, 13.82% at Day 60, 95% CI 6.82–20.82%, P = 0.0001 and 8.95% at Day 90, 95% CI 2.06–15.85%, P = 0.01). We also found that there were no significant differences in new-onset major vascular events (P = 0.8502) and serious adverse events (P = 0.9105) between DHI and placebo. After performing the RNA sequencing in 62 selected patients, we developed a systemic modular approach to identify differentially expressed modules (DEMs) of DHI with the Zsummary value less than 0 compared with the control group, calculated by weighted gene co-expression network analysis (WGCNA), and sketched out the basic framework on a modular map with 25 functional modules targeted by DHI. Furthermore, the effective therapeutic module (ETM), defined as the highest correlation value with the phenotype alteration (ΔSAQ-AF, the change in SAQ-AF at Day 30 from baseline) calculated by WGCNA, was identified in the population with the best effect (ΔSAQ-AF ≥ 40), which is related to anticoagulation and regulation of cholesterol metabolism. We assessed the modular flexibility of this ETM using the global topological D value based on Euclidean distance, which is correlated with phenotype alteration (r2: 0.8204, P = 0.019) by linear regression. Our study identified the anti-angina therapeutic module in the effective population treated by the multi-target drug. Modular methods facilitate the discovery of network pharmacological mechanisms and the advancement of precision medicine. (ClinicalTrials.gov identifier: NCT01681316).

Background Oncolytic viruses (OVs) are considered a promising therapeutic alternative for cancer. However, OVs could activate the host innate immunity, then impair the viral propagation in tumor cells. In this study, we explored the effect of propranolol, a non-selective β-blocker, on the antitumor efficacy of T1012G virus in gastric cancer models. Methods The proliferation of gastric cancer cells treated with monotherapy or combination treatment was detected by CCK8 cell proliferation assay. The effect of propranolol was further evaluated by in vitro viral replication assays. In vivo tumor xenograft experiments were used to observe the effect of combination therapy on gastric cancer growth in mice. The expression levels of viral proteins and interferon responsive genes were detected in the gastric cancer cell lines treated with combined treatment by western blot. The impact of propranolol on IFN-α/β-mediated inhibition of viral propagation and the expression of antiviral gene PKR was detected by viral replication assays and western blot. Results Cell viability assay detected a 97.9% decrease of T1012G IC50 in HGC-27 when it was pretreated with propranolol along with a sevenfold increase of virus titers compared with T1012G only group (P 3 vs. 1118 ± 210.0 mm3, P P P P P P P P Conclusions In summary, β-blocker pretreatment could improve the propagation and therapeutic efficacy of T1012G in human gastric cancer by regulating STAT3-PKR signaling cascade, even in the presence of type I IFNs. These data support new strategies of improving the efficacy of OVs in gastric cancer.

Perivascular epithelioid cell neoplasms (PEComas) are a rare type of mesenchymal neoplasm and their preoperative diagnosis is challenging. In this study, we summarized the experience from a single medical center to study the examinations, clinical presentations, and pathological and histological characteristics of PEComas in the liver in order to optimize overall understanding of the diagnosis and treatment of these neoplasms.We conducted a retrospective analysis to investigate the clinical and pathological characteristics as well as imaging presentations of 75 patients diagnosed with hepatic PEComa in The First Affiliated Hospital of Zhejiang University between April 2010 and April 2020.Among the 75 patients, 52 were women, and the median age was 48 years. Most patients had no specific symptoms, and two were admitted to the hospital for a second time owing to relapse. All patients underwent surgical resection. Histologically, 38 patients had classical angiomyolipoma (AML) and 37 had epithelioid AML. The PEComas were accompanied by positive immunohistochemical expression of HMB45, Melan-A, and smooth muscle actin. Follow-up data were obtained from 47 of the total 75 patients, through October 2020. Two patients had metastasis after surgery.AML is the most common type of hepatic PEComa. There are no specific symptoms of hepatic PEComa, and serological examinations and imaging modalities for accurate preoperative diagnosis are lacking. Epithelioid AML should be considered a tumor of uncertain malignant potential; however, the prognosis of PEComa after resection is promising.

Purpose Regarding the interpersonal influence of customer anger on frontline employees (FLEs) in service encounters, existing findings remain mixed. Building on emotion as a social information model and appraisal theory, this study aims to focus on two dimensions of customer anger – intensity and relevance with FLEs and examined their divergent effects on FLEs’ immediate recovery performance. Design/methodology/approach This study conducted a questionnaire survey of 366 Chinese FLEs in the hospitality and tourism industries. Hierarchical regressions and bootstrap analysis for nonlinear mediated relationships were used to test the hypotheses. Findings The results suggested a U-shaped curvilinear relationship between the intensity of customer anger and FLEs’ recovery performance and a positive linear relationship between relevance with FLEs of customer anger and FLEs’ recovery performance. Moreover, the mediating effects of FLEs’ emotional anger and cognitive perceived threat were confirmed. Practical implications Service managers should improve FLEs’ awareness of unconscious emotional contagion and encourage them to shoulder responsibility actively even if customer anger is not related to them. In addition, complaining customers can learn how to strategically express anger to get good remedies. Originality/value This paper examines the divergent effects of two dimensions of customer anger on FLEs, advancing the understanding of customer anger in the service interaction. It is also the first to suggest the U-shaped nonlinear effect of customer anger intensity on employees’ service outcomes and its underlying mechanisms, reconciling mixed findings.

We aimed to investigate the mechanisms of renal fibrosis and explore the effect of CD4+CD25+Foxp3+ regulatory T cells (Treg) on renal fibrosis after the obstruction was removed.Fifty-five C57BL/6 mice were randomly divided into three groups: the unilateral ureteral obstruction (UUO) group, the relief for unilateral ureteral obstruction (RUUO) group, and the RUUO+Treg group. Renal fibrosis indexes of RUUO mice were evaluated using hematoxylin and eosin (HE) and, Masson staining and immunohistochemistry after CD4+CD25+Treg cells were injected into the tail vein at the moment of recanalization. We detected the levels of Treg, M1, and M2 markers by flow cytometry, and the levels of transforming growth factor (TGF)-β1, interleukin (IL)-1β, IL-6 and IL-10 using ELISA.The tubular necrosis score, AO value of α-SMA (smooth muscle actin), and collagen area on the 3rd and 14th days post RUUO were up-regulated compared with the 7th day post RUUO (P0.05). After injection of Treg via tail vein, the tubular necrosis score, AO value of α-SMA, TGF-β1 level, and collagen area in the RUUO+Treg group on the 14th day were down-regulated compared with the RUUO group (P0.05). Moreover, Treg could transform M1 macrophages into M2 macrophages, manifesting as up-regulated expression of CD206 compared with the RUUO group (P0.05). Treg could also down-regulate the secretion of IL-6 and IL-1β while up-regulating the secretion of IL-10 in vitro compared with the M1 group (P0.05).The kidney could deteriorate into a state of injury and fibrosis after the obstruction was removed, and Treg could effectively protect the kidney function.

Cadmium-based quantum dots (Cd-QDs) show decent performance for lighting applications due to good color saturation, an excellent high quantum yield, and a narrow full-width at half-maximum. However, the intrinsic toxicity of Cd is a major hindrance to related applications, especially in the biological field. ZnSe, with a band gap of 2.7 eV and lower toxicity than CdSe or CdS, is promising as a blue luminescent material. Herein, we mainly reported the preparation and luminescence properties of nanostructured ZnSe/ZnS multilayer thin films with bright blue photoluminescence. The photoluminescence spectrum contained two emission peaks, located at about 442 nm (near band-edge emission) and 550 nm (defect-related emission), respectively. More importantly, the photoluminescence performance and decay were explored in detail through low-temperature photoluminescence spectra. In addition, the nanostructured ZnSe/ZnS multilayer thin films showed favorable photostability.

Cyclosporin a (CsA) was characterized by a narrow therapeutic window and high interindividual pharmacokinetic variability. In this study, we aimed to identify the association of CYP3A4, ABCB1, ABCC...

Hepatocellular Carcinoma (HCC) patients usually have a high rate of relapse and metastasis. Alcohol, a risk factor for HCC, promotes the aggressiveness of HCC. However, the basic mechanism is still unclear. We used HCC cells and an orthotopic liver tumor model of HCC-LM3 cells for BALB/C nude mice to study the mechanism of alcohol-induced HCC progression. We showed that chronic alcohol exposure promoted HCC cells metastasis and pulmonary nodules formation. First, we identified miR-22-3p as an oncogene in HCC, which promoted HCC cells stemness, tumor growth, and metastasis. Further, we found that miR-22-3p directly targeted TET2 in HCC. TET2, a dioxygenase involved in cytosine demethylation, has pleiotropic roles in hematopoietic stem cells self-renewal. In clinic HCC specimen, TET2 expression was not only decreased by alcohol consumption, but also inversely correlated with miR-22-3p levels. Then, we demonstrated that TET2 depletion promoted HCC cells stemness, tumor growth and metastasis. Furthermore, we identified that β-catenin was an upstream activator of miR-22-3p. In conclusion, this study suggests that chronic alcohol exposure promotes HCC progression and β-catenin/miR-22-3p/TET2 regulatory axis plays an important role in alcohol-promoted HCC malignancy.

Generative models have been applied in many fields and can be evaluated with many methods. In the evaluation of generative models, the proper evaluation metric varies with the application field. Therefore, the evaluation of generative adversarial networks is inherently challenging. In this study, conditional deep convolutional generative adversarial networks were applied in mechanical fault diagnosis and then evaluated. We proposed three evaluation metrics of conditional deep convolutional generative adversarial networks: Jensen-Shannon divergence, kernel maximum mean discrepancy, and the 1-nearest neighbor classifier which were used to distinguish generated samples from real samples, test mode collapsing and detect overfitting based on the dataset of Electronic Engineering Laboratory of Case Western Reserve University and the planetary gearbox dataset measured in the laboratory. The Jensen-Shannon divergence could not well distinguish generated samples from real samples. However, the two metrics (maximum mean discrepancy and 1-nearest neighbor classifier) well-distinguished generated samples from real samples, thus verifying the applicability of conditional deep convolutional generative adversarial networks in the field of mechanical diagnosis.

Intelligent wearable devices have many characteristics such as convenience, intelligence and real-time. Through the detection and analysis of wearable devices and the real-time transmission of data, it can test vital signs and movement and other important information, monitor human body and provide data support for health status. According to the development of wearable devices in recent years, this article summarizes the different ways to wear wearable devices, the common materials for wearable devices and the different sensing modes of wearable devices. Then its applications in physiological and motion detection are also presented. Finally, the challenges and opportunities faced by the wearable devices are analyzed and prospected.

Enterovirus A71 (EV-A71) inactivated vaccines have been widely inoculated among children in Kunming City after it was approved. However, there was a large-scale outbreak of Enteroviruses (EVs) infection in Kunming, 2018. The epidemiological characteristics of HFMD and EVs were analysed during 2008–2018, which are before and three years after EV-A71 vaccine starting to use. The changes in infection spectrum were also investigated, especially for severe HFMD in 2018. The incidence of EV-A71 decreased dramatically after the EV-A71 vaccine starting use. The proportion of non-CV-A16/EV-A71 EVs positive patients raised to 77.17–85.82%, while, EV-A71 and CV-A16 only accounted for 3.41–7.24% and 6.94–19.42% in 2017 and 2018, respectively. CV-A6 was the most important causative agent in all clinical symptoms (severe HFMD, HFMD, Herpangina and fever), accounting from 42.13% to 62.33%. EV-A71 only account for 0.36–2.05%. In severe HFMD, CV-A6 (62.33%), CV-A10 (11.64%), and CV-A16 (10.96%) were the major causative agent in 2018. EV-A71 inactivated vaccine has a good protective effect against EV-A71 and induced EVs infection spectrum changefully. EV-A71 vaccine has no or insignificant cross-protection effect on CV-A6, CV-A10, and CV-A16. Herein, developing 4-valent combined vaccines is urgently needed.

In the era of paper-based contract, a lot of time, human labor and expenses are required to handle the process of contract drafting, contract signing, contract execution, and payment settlement. The emerging of electronic contract enhances the tedious signing process of paper-based contract and improves the efficiency of contract management. However, due to the centralized system architecture and the database-based storage schema, the stored contract data is at high risk of information leaking, data tampering and hacker attacks. In this study, we introduce Blockchain technology to the contract management, and develop a process-oriented contract management system (BEcontractor) for a Hangzhou-located power grid enterprise X, aiming to solve a series of security issues existing in the traditional electronic contract system. By deploying BEcontractor, procurement activities could be resumed online among X and its nation-widely commodity suppliers during COVID-19 epidemic. Up to September 2020, 6336 electronic contracts have been signed, with an accumulated amount of $\yen ~6.5$ billion. It is showed that the cost for accomplishing the contract signing process was significantly reduced, and the payment period was shortened from three months to around one month.

Aim To evaluate the diagnostic performance of contrast-enhanced ultrasound (CEUS) for Breast Imaging-Reporting and Data System for Ultrasound (US-BI-RADS) 3 and 4 lesions with calcifications. Materials and methods A retrospective study of 168 breast lesions with calcifications detected on both mammography and conventional ultrasonography (US) in 152 patients were categorised as US-BI-RADS 3–4 at US between June 2009 and June 2018. CEUS scores were obtained based on a CEUS five-point scoring system. The combination of US-BI-RADS and CEUS scores created the Rerated BI-RADS (referred to as CEUS-BI-RADS). All results were compared with the histological findings. The diagnostic performances of US and CEUS-BI-RADS were compared. Results The diagnostic sensitivity, specificity, and accuracy of US were 81.8% (95% confidence interval [CI]: 71.6%, 92%), 85% (95% CI: 78.4%, 91.5%), and 83.9% (95% CI: 78.4%, 89.5%), respectively, while those for CEUS-BI-RADS were 98.2% (95% CI: 94.7%, 100%), 90.3% (95% CI: 84.8%, 95.7%), and 92.9% (95% CI: 89%, 96.8%), respectively. The diagnostic sensitivity and accuracy values of CEUS-BI-RADS greatly improved compared with those of US (p=0.003 and p=0.004, respectively). The areas under the receiver operating characteristic (ROC) curves for US and CEUS-BI-RADS were 0.888 (95% CI: 0.840, 0.936) and 0.963 (95% CI: 0.936, 0.989), respectively. The diagnostic efficacy of CEUS-BI-RADS was significantly higher than that of US alone (p=0.004). Conclusion CEUS-BI-RADS significantly improves the diagnostic accuracy for breast US-BI-RADS 3 and 4 lesions with calcifications compared with US.

PURPOSE Although MET exon 14 ( METex14)–altered lung cancers were first identified more than a decade and a half ago, the frequency of CNS metastatic disease remains poorly defined. Furthermore, the seminal trial of crizotinib in these patients (PROFILE 1001) did not report patterns of CNS response or progression. PATIENTS AND METHODS Patients with pathologically confirmed, advanced non–small-cell lung cancers (NSCLC) harboring a METex14 alteration by targeted DNA/RNA sequencing were studied. The incidence of brain metastases and the outcomes of MET inhibition with crizotinib were analyzed. RESULTS Eighty-three patients with METex14-altered metastatic NSCLC were identified. The incidence of CNS metastases at diagnosis was 17% (95% CI, 10% to 27%). The lifetime incidence was 36% (95% CI, 26% to 47%); 83% of patients had parenchymal disease, and 17% had leptomeningeal disease. The probability of having brain metastasis at 1, 2, and 3 years was 24%, 35%, and 38%, respectively. Fifty-four patients received crizotinib. The median time to radiologic CNS progression was 5.8 months (range, 3.7-20.0 months). Patterns of crizotinib progression were as follows: intracranial only in 10% of patients, intracranial and extracranial in 12%, and extracranial only in 78%. In patients with brain metastases before treatment, the median time on crizotinib was 7.5 months (range, 7.2-11.7 months). CONCLUSION CNS metastases, including leptomeningeal disease, occurred in more than a third of patients with METex14-altered lung cancers. In crizotinib-treated patients with or without CNS metastases, CNS failure was seen in less than a quarter of patients on progression.

To the Editor: Medically unexplained physical symptoms (MUPS) and related disorders are especially common in healthcare-seeking populations. A recent meta-analysis revealed the prevalence of somatoform disorders of 34.8% (by International Classification of Diseases) and 26.2% (by Diagnostic and Statistical Manual of Mental Disorders [DSM]) in primary care patients. Further, at least one medically unexplained symptom was detected among 40% to 49% of primary care patients using questionnaires.

Acute lung injury (ALI) involves series of inflammatory pathologies and cause high morbidity. Salviplenoid A (SA) was a new sesquiterpenoid from the traditional inflammatory herb Salvia plebeia. In our previous study, SA exhibited antiinflammatory activity in RAW264.7 cells. However, the extensive effects of SA in human cells and in vivo and the active mechanisms are unclear. Thus, in this study, we sought to access its effects in vitro and in vivo and to investigate its mechanisms. SA was proved to inhibit the induction of proinflammatory cytokines in human cell types, including pulmonary epithelial cells and endothetial cells. It also depressed monocyte adhesion. Moreover, SA potently attenuated the acute lung inflammation in the LPS-induced mouse model shown by down-regulation of proinflammatory mediators, inhibition of polymorphonuclear neutrophil infiltration, and alleviation of related symptoms like alveolar congestion and mucus secretion. Further evaluation confirmed that SA regulated NF-κB pathway by inhibiting the IκB-α phosphorylation. And it markedly mediated Nrf2/HO-1 pathway by activating the Nrf2/HO-1 expression and promoting Nrf2 nuclear translocation. Therefore, SA could attenuate acute lung inflammation via suppressing NF-κB and activating Nrf2, which provide a theoretical basis for the potential application of SA in clinic.

PURPOSE: To assess the value of conventional ultrasound (US), contrast-enhanced ultrasound (CEUS) and mammography in the diagnosis of breast lesions with calcifications. METHODS: A total of 87 breast lesions with calcification were subjected to US, CEUS and mammography and divided into 3 groups: Group A (all cases), Group A1 (31 cases who underwent US and CEUS first followed by mammography), and Group A2 (56 cases who underwent mammography first followed by US and CEUS). A receiver operating characteristic (ROC) curve analysis was performed to evaluate the diagnostic efficacy of different methods in different groups. RESULTS: In Group A, the area under the ROC curve (AUROC) of CEUS were 0.937, which were significantly higher than that of mammography (p 0.05). In Group A2, the AUROC of CEUS were 0.987, which were significantly higher than that of mammography and US (p

Structured Abstract Background Patients with lung cancers may have disproportionately severe COVID-19 outcomes. Understanding the patient-specific and cancer-specific features that impact severity of COVID-19 may inform optimal cancer care during this pandemic. Patients and methods We examined consecutive patients with lung cancer and confirmed diagnosis of COVID-19 (n=102) at a single center from March 12-May 6, 2020. Thresholds of severity were defined a priori as hospitalization, ICU/intubation/DNI (a composite metric of severe disease including ICU stay, intubation and invasive mechanical ventilation, and/or transition to do not intubate [DNI]), or death. Recovery was defined as >14 days from COVID-19 test and >3 days since symptom resolution. HLA alleles were inferred from MSK-IMPACT (n=46) and compared to controls with lung cancer and no known non-COVID-19 (n=5166). Results COVID-19 was severe in patients with lung cancer (62% hospitalized, 25% died). Although severe, COVID-19 accounted for a minority of overall lung cancer-deaths during the pandemic (11% overall). Determinants of COVID-19 severity were largely patient-specific features, including smoking status and chronic obstructive pulmonary disease (Odds ratios for severe COVID-19 2.9, 95% CI 1.07-9.44 comparing the median [23.5 pack-years] to never and 3.87, 95% CI 1.35-9.68, respectively). Cancer-specific features, including prior thoracic surgery/radiation and recent systemic therapies did not impact severity. HLA supertypes were generally similar in mild or severe cases of COVID-19 compared to non-COVID-19 controls. Most patients recovered from COVID-19, including 25% patients initially requiring intubation. Among hospitalized patients, hydroxychloroquine did not improve COVID-19 outcomes. Conclusion COVID-19 is associated with high burden of severity in patients with lung cancer. Patient-specific features, rather than cancer-specific features or treatments, are the greatest determinants of severity., Highlights • COVID-19 is associated with high burden of severity in patients with lung cancer. • Patient-specific features, rather than cancer-specific features or treatments, are the greatest determinants of severity.

In order to provide the scientific basis for Camellia oleifera nutrient diagnosis and fertilizer formulation, the correlation between soil nutrients and nutrient elements in different organs of Camellia oleifera was studied in ten-year-old Camellia oleifera in Changning city. The results showed that among the nutrient elements, the content of N and P were the highest and lowest in various organs, respectively. Correspondingly, the highest content of macro-element in the soil was Ca. Besides, there were diverse relations among nutrients in soil and those in different organs of Camellia oleifera. Soil nutrients were most closely associated with that of stem, so was soil N, Zn, Mn, Pb and K with the plant nutrients. In addition, soil exchangeable Mn content was positively correlated with nutrients of different organs. Moreover, soil N showed highly significant correlation with N content in stem while soil Cd content was negatively correlated with Cd content of all organs. Thus, there prevails a complex interaction of nutrient elements in the soil and exists a synergy or/and antagonism effect among of elements in plants. Consequently, the understanding of effect of interaction between different elements might provide better idea for achieving the precise fertilization, which could further reduce costs and increase production.

It is expected that advancements in communication technology can promote international trade by reducing transaction costs, improving efficiency, and moderating information asymmetry. Moreover, intercultural miscommunication caused by cultural differences generates costs from communication breakdowns during international trade. Using bilateral trade data from China and its major trading partners, this study not only provides further empirical evidence to support these claims but also examines the joint effect of those two factors on international trade, which have not been addressed in the literature. This study reveals the mixed results of the joint effects of intercultural miscommunication and the three factors of communication technology (access, use, and skills). More specifically, individualistic behaviours and masculine attitudes contribute the most to the negative effect on the relationship between international trade and communication technology access and use. In contrast, communication technology skills interact with intercultural miscommunication in different ways.

The rapid spread of coronavirus SARS-CoV-2 greatly threatens global public health but no prophylactic vaccine is available. Here, we report the generation of a replication-incompetent recombinant serotype 5 adenovirus, Ad5-S-nb2, carrying a codon-optimized gene encoding Spike protein (S). In mice and rhesus macaques, intramuscular injection with Ad5-S-nb2 elicits systemic S-specific antibody and cell-mediated immune (CMI) responses. Intranasal inoculation elicits both systemic and pulmonary antibody responses but weaker CMI response. At 30 days after a single vaccination with Ad5-S-nb2 either intramuscularly or intranasally, macaques are protected against SARS-CoV-2 challenge. A subsequent challenge reveals that macaques vaccinated with a 10-fold lower vaccine dosage (1 × 1010 viral particles) are also protected, demonstrating the effectiveness of Ad5-S-nb2 and the possibility of offering more vaccine dosages within a shorter timeframe. Thus, Ad5-S-nb2 is a promising candidate vaccine and warrants further clinical evaluation., A vaccine protecting from SARS-CoV-2 infection is needed. Here the authors generate a replication-incompetent adenovirus based vaccine expressing SARS-CoV-2 spike, show protection from infection in non-human primates, and analyze the immune response after intramuscular and intranasal vaccination.

Background Esophagectomy is a pivotal curative modality for localized esophageal or esophagogastric junction cancer (EC or EJC). Postoperative anastomotic leakage (AL) remains problematic. The use of fibrin sealant (FS) may improve the strength of esophageal anastomosis and reduce the incidence of AL. Aim To assess the efficacy and safety of applying FS to prevent AL in patients with EC or EJC. Methods In this single-arm, phase II trial (Clinicaltrial.gov identifier: NCT03529266), we recruited patients aged 18-80 years with resectable EC or EJC clinically staged as T1-4aN0-3M0. An open or minimally invasive McKeown esophagectomy was performed with a circular stapled anastomosis. After performing the anastomosis, 2.5 mL of porcine FS was applied circumferentially. The primary endpoint was the proportion of patients with AL within 3 mo. Results From June 4, 2018, to December 29, 2018, 57 patients were enrolled. At the data cutoff date (June 30, 2019), three (5.3%) of the 57 patients had developed AL, including two (3.5%) with esophagogastric AL and one (1.8%) with gastric fistula. The incidence of anastomotic stricture and other major postoperative complications was 1.8% and 17.5%, respectively. The median time needed to resume oral feeding after operation was 8 d (Interquartile range: 7.0-9.0 d). No adverse events related to FS were recorded. No deaths occurred within 90 d after surgery. Conclusion Perioperative sealing with porcine FS appears safe and may prevent AL after esophagectomy in patients with resectable EC or EJC. Further phase III studies are warranted.

Recently, software-defined Industrial Internet of Things (SDIIoT), the integration of software-defined networking (SDN) and Industrial Internet of Things (IIoT), has emerged. It is perceived as an effective way to manage IIoT dynamically. Aiming to improve the scalability and flexibility of SDIIoT, multi-SDN has been applied to form a physically distributed control plane to handle a large amount of data generated by industrial devices. However, as the core of multi-SDN, reaching consensus among multiple SDN controllers is a thorny issue. To meet the required design principle, this article proposes a blockchain-enabled distributed SDIIoT to synchronize local views between distinct SDN controllers and finally reach the consensus of the global view. On the other hand, both the cryptographic operations of blockchain and the noncryptographic tasks have access to the same computational resource pool of mobile edge cloud (MEC). In order to optimize the system energy efficiency, we adaptively allocate computational resources and the batch size of the block by jointly considering the trust features of SDN controllers and the resource requirements of noncryptographic operations. To implement the truly distributed manner of blockchain, we describe our problem as a partially observable Markov decision process (POMDP) and propose a novel deep reinforcement learning (DRL) approach to solve it. In the simulation results, we compare three different protocols of blockchain and show the effectiveness of our scheme in each of them.

Due to the real working conditions, the collected mechanical fault datasets are actually limited and always highly imbalanced, which restricts the diagnosis accuracy and stability. To solve these problems, we present an imbalanced fault diagnosis method based on the generative model of conditional-deep convolutional generative adversarial network (C-DCGAN) and provide a study in detail. Deep convolutional generative adversarial network (DCGAN), based on traditional generative adversarial networks (GAN), introduces convolutional neural network into the training for unsupervised learning to improve the effect of generative networks. Conditional generative adversarial network (CGAN) is a conditional model obtained through introducing conditional extension into GAN. C-DCGAN is a combination of DCGAN and CGAN. In C-DCGAN, based on the feature extraction ability of convolutional networks, through the structural optimization, conditional auxiliary generative samples are used as augmented data and applied in machine fault diagnosis. Two datasets (Bearing dataset and Planetary gear box dataset) are carried out to validate. The simulation experiments showed that the improved performance is mainly due to the generated signals from C-DCGAN to balance the dataset. The proposed method can deal with imbalanced fault classification problem much more effectively. This model could improve the accuracy of fault diagnosis and the generalization ability of the classifier in the case of small samples and display better fault diagnosis performance.

The PACIFIC trial of durvalumab administered for 1 year to patients with stage III lung cancers has set a new standard of care. PACIFIC established the role of immune checkpoint inhibitors (ICIs) for individuals with inoperable and unresectable locally advanced lung cancers that achieve disease control from concurrent chemoradiation. For patients with resectable and operable disease, ICIs administered before surgery, either alone (JHU/MSK, LCMC3, and NEOSTAR) or in combination with chemotherapy (Columbia/MGH and NADIM), have yielded high rates of major pathologic response in resection specimens, an outcome measure that correlates with improved progression-free survival and overall survival. These results have brought forth the dilemma of how to choose the optimal local therapy—either definitive concurrent chemoradiation or surgery—to use with an ICI for patients with stage III lung cancers that are both operable and resectable. Here, we review the data that support the use of each local therapy. Recent successes have also raised the possibility that using ICIs in patients with earlier stages of lung cancer will enhance curability. Randomized trials are underway; however, until they read out, physicians must choose between local and systemic therapies on the basis of the information we have today. Research demonstrates that using surgery, radiation, chemotherapy, and ICIs improve all efficacy outcomes and curability. All modalities should be considered in every patient with locally advanced lung cancer. It is imperative that a multimodality discussion that includes the possible addition of ICIs takes place to choose the best modality and sequence of therapies for each patient.

Background Serum miRNA was once found as potential disease survival index,thus we investigated the role of miRNA in predicting prognosis in loco-regionally advanced NPC patients treated with CCRT. Methods This study included two phases: (i) We enrolled 3 NPC patients with recurrence or distant metastasis (experimental group, EG) and 3 NPC patients in clinical remission (control group, CG),who were treated with CCRT within 5 years. The paired serum was collected before and after treatment and biomarkers were discovered by LNA-TaqMan Human MicroRNA Arrays. (ii) we used the bioinformatic analysis, marker selection and an independent validation by qRT-PCR to analyse the serums of 29 NPC patients with recurrent disease or distant metastasis and 19 NPC patients in clinical remission treated with CCRT. Using the Kaplan-Meier method, log-rank test and Cox regression model to estimate the accuracy of the miRNAs to predict PFS and OS, and identified factors significantly associated with prognosis, respectively. Results Using fold change≥2.0 or ≤ 0.5 and p ≤ 0.05 as cutoff levels, we identified 1 up-regulated and 6 down-regulated miRNAs, 1 up-regulated and 9 down-regulated miRNAs in EG versus CG before and after CCRT, respectively. After these down-regulated miRNAs were dealed with bioinformatics analysis and normalization, only 5 different miRNAs were significantly reduced, which there were no significant difference in the expression of miRNA-26b, miRNA-29a and miRNA-125b before CCRT, and the expression of miRNA-143 and miRNA-29b after CCRT in the serum samples of 48 NPC patients. Based on this, we calculated a risk score with the expression of miRNA-26b、miRNA-29a、miRNA-125b、miRNA-29b、miRNA-143 and then classified patients as high or low risk group. Cox regression model suggested that combining miRNA-29a and miRNA-125b before CCRT with miRNA-26b after CCRT was independent prognostic factors for PFS (HR = 3.149, 95%CI:1.018–9.115, p = 0.034), whereas combining the former two is independent for OS (HR = 5.146, 95%CI:1.674–15.817, p = 0.04). Conclusions For loco-regionally advanced NPC patients treated with CCRT, especially high-risk patients- serum miRNAs, such as miRNA-29a, miRNA-125b and miRNA-26b etc., play an important role in predicting prognosis factors of PFS and OS, which will contribute to the strategic direction for future research.

Introduction: Auditory brainstem response (ABR) is one of the commonly used methods in clinical settings to evaluate the hearing sensitivity and auditory function. The current ABR measurement usually adopts click sound as the stimuli. However, there may be partial ABR amplitude attenuation due to the delay characteristics of the cochlear traveling wave along the basilar membrane. To solve that problem, a swept-tone method was proposed, in which the show-up time of different frequency components was adjusted to compensate the delay characteristics of the cochlear basilar membrane; therefore, different ABR subcomponents of different frequencies were synchronized. Methods: The normal hearing group, moderate sensorineural hearing loss group, and severe sensorineural hearing loss group underwent click ABR and swept-tone ABR with different stimulus intensities. The latencies and amplitudes of waves I, III, and V in 2 detections were recorded. Results: It was found that the latency of each of the recorded I, III, and V waves detected by swept-tone ABR was shorter than that by click ABR in both the control group and experimental groups. In addition, the amplitude of each of the recorded I, III, and V waves, except V waves under 60 dB nHL in the moderate sensorineural hearing loss group, detected by swept-tone ABR was larger than that by click ABR. The results also showed that the swept-tone ABR could measure the visible V waves at lower stimulus levels in the severe sensorineural hearing loss group. Conclusion: Swept-tone improves the ABR waveforms and helps to obtain more accurate threshold to some extent. Therefore, the proposed swept-tone ABR may provide a new solution for better morphology of ABR waveform, which can help to make more accurate diagnosis about the hearing functionality in the clinic.

Red yeast rice (RYRP) has been utilized for coloring food, brewing wine, and preserving meat, which is also used as a folk medicine for centuries. In this study, a water-soluble nonstarch polysaccharide from RYRP was extracted by using ultrasonic-assisted extraction method. By using the Box-Behnken design to optimize the parameters for extracting the RYRP, the maximum extraction yield (3.37 ± 0.78%) was obtained under the optimal extraction conditions as follows: ratio of water to raw material (40 mL/g), extraction temperature (62 °C), extraction time (75 Min), and ultrasonic power (200 W). Moreover, monosaccharide composition analysis showed that RYRP was consisted of mannose, glucosamine, glucose, and galactose with a molar ratio of 0.152:0.015:1:0.149. The molecular weight distribution analysis showed that the average molecular weight of the RYRP fraction was about 3.49 × 103 Da. Furthermore, RYRP exhibited significant antioxidant activities in vitro and the gastrointestinal-protective effect in vivo using gastrointestinal disorders model mice. RYRP could be explored as a potential source in the pharmaceutical and functional food industries.

Pancreatitis and alcoholic pancreatitis are serious health concerns, and there is an urgent need for effective treatment strategies. Alcohol is a known etiological factor for pancreatitis, including acute pancreatitis (AP) and chronic pancreatitis (CP). Excessive alcohol consumption induces many pathological stress responses; of particular note is endoplasmic reticulum (ER) stress and adaptive unfolded protein response (UPR). ER stress results from the accumulation of unfolded/misfolded protein in the ER and is implicated in the pathogenesis of alcoholic pancreatitis. Here we summarize the possible mechanisms by which ER stress contributes to alcoholic pancreatitis. We also discuss potential approaches targeting ER stress and UPR for developing novel therapeutic strategies for the disease.

BACKGROUND We aimed to explore the association between periodontitis and lung function in the United States of America. METHODS The data was based on the National Health and Nutrition Examination Survey (NHANES) 2009-2012. Periodontitis was defined following the CDC/AAP (Centers for Disease Control and Prevention/American Academy of periodontology) classification. Lung function measurements included forced expiratory volume in one second (FEV1) , forced vital capacity (FVC) , and FEV1/FVC ratio. Linear regression and binary logistic regression were used to explore the association between periodontitis and lung function measurements. Restricted cubic spline was used to assess the dose-response relationships between the mean attachment loss, the mean probing depth and spirometry-defined airflow obstruction (FEV1/FVC < 0.7) . RESULTS A total of 6313 adults aged 30 years or older were included. Compared to those with non-periodontitis, the multivariate-adjusted odds ratios (ORs) of airflow obstruction for moderate and severe periodontitis were 1.38 (95%CI: 1.01-1.75) and 1.47 (95%CI: 1.06-2.01) , the β coefficients of FEV1 for moderate and severe periodontitis were -130.16 (95%CI: -172.30 to -88.01) and -160.46 (95%CI: -249.94 to -70.97) , the β coefficients of FVC for moderate and severe periodontitis were -100.96 (95%CI: -155.08 to -46.85) and -89.89 (95%CI: -178.45 to -1.33) , the β coefficients of FEV1/FVC for moderate and severe periodontitis were -0.01 (95%CI: -0.02 to -0.01) and -0.02 (95%CI: -0.03 to -0.01) . In stratified analyses, the multivariate-adjusted odds ratios of airflow obstruction for the moderate and severe periodontitis were 1.27 (95%CI: 0.84-1.93) and 2.31 (95%CI: 1.10-4.83) in former smokers, 1.84 (95%CI: 1.03-3.30) and 1.79 (95%CI: 1.02-3.16) in current smokers, with no significant association observed in never smokers. Mean clinical attachment loss and mean probing depth were negatively associated with FEV1, FVC and FEV1/FVC in never, former and current smokers. Dose-response relationship analysis showed that the risk of airflow obstruction increased with increasing mean clinical attachment loss and mean probing depth, and showed a non-linear dose-response relationship. CONCLUSION Our study suggested that moderate and severe periodontitis might be associated with the decline of lung function in the United States of America. This article is protected by copyright. All rights reserved.

Primary cutaneous localized amyloidosis (PCLA) is a severely pruritic and potentially disfiguring disorder which impact greatly on a patient’s quality of life. There is no ‘silver bullet’ cure for ...

Oncolytic viruses (OVs) are considered a promising therapeutic alternative for cancer. However, despite the development of novel OVs with improved efficacy and tumor selectivity, their limited efficacy as monotherapeutic agents remains a significant challenge. This study extended our previously observed combination effects of propranolol, a nonselective β-blocker, and the T1012G oncolytic virus into colorectal cancer models. A cell viability assay showed that cotreatment could induce synergistic killing effects on human and murine colorectal cell lines. Moreover, cotreatment caused sustained tumor regression compared with T1012G monotherapy or propranolol monotherapy in human HCT116 and murine MC38 tumor models. The propranolol activity was not via a direct effect on viral replication in vitro or in vivo. Western blotting showed that cotreatment significantly enhanced the expression of cleaved caspase-3 in HCT116 and MC38 cells compared with the propranolol or T1012G alone. In addition, propranolol or T1012G treatment induced a 35.06% ± 0.53% or 35.49% ± 2.68% reduction in VEGF secretion in HUVECs (p < 0.01/p < 0.01). Cotreatment further inhibited VEGF secretion compared with the monotherapies (compared with propranolol treatment: 75.06% ± 1.50% decrease, compared with T1012G treatment: 74.91% ± 0.68%; p＜0.001, p < 0.001). Consistent with the in vitro results, in vivo data showed that cotreatment could reduce Ki67 and enhance cleaved caspase 3 and CD31 expression in human HCT116 and murine MC38 xenografts. In summary, β-blockers could improve the therapeutic potential of OVs by enhancing oncolytic virus-mediated killing of colorectal cancer cells and colorectal tumors.

AimWe retrospectively analyzed the distribution of distant lymph node metastasis and its impact on prognosis in patients with metastatic NPC after treatment.MethodsFrom 2010 to 2016, 219 NPC patients out of 1,601 (182 from the Affiliated Cancer Hospital and Institute of Guangzhou Medical University, and 37 from the Affiliated Dongguan Hospital, Southern Medical University) developed distant metastasis after primary radiation therapy. Metastatic lesions were divided into groups according to location: bones above the diaphragm (supraphrenic bone, SUP-B); bones below the diaphragm (subphrenic bone, SUB-B); distant lymph nodes above the diaphragm (supraphrenic distant lymph nodes, SUP-DLN); distant lymph nodes below the diaphragm (subphrenic distant lymph nodes, SUB-DLN), liver, lung, and other lesions beyond bone/lung/distant lymph node above the diaphragm (supraphrenic other lesions, SUP-OL); other lesions beyond bone/liver/distant lymph node below the diaphragm (subphrenic other lesions, SUB-OL); the subtotal above the diaphragm (supraphrenic total lesions, SUP-TL); and the subtotal below the diaphragm (subphrenic total lesions, SUB-TL). Kaplan–Meier methods were used to estimate the probability of patients’ overall survival (OS). Univariate and multivariate analyses were applied using the Cox proportional hazard model to explore prediction factors of OS.ResultsThe most frequent metastatic locations were bone (45.2%), lung (40.6%), liver (32.0%), and distant lymph nodes (20.1%). The total number of distant lymph node metastasis was 44, of which 22 (10.0%) were above the diaphragm, 18 (8.2%) were below the diaphragm, and 4 (1.8%) were both above and below the diaphragm. Age (HR: 1.02, 95% CI: 1.00, 1.03, p = 0.012), N stage (HR: 1.26, 95% CI: 1.04, 1.54, p = 0.019), number of metastatic locations (HR: 1.39, 95% CI: 1.12, 1.73, p = 0.003), bone (HR: 1.65, 95% CI: 1.20, 2.25, p = 0.002), SUB-B (HR: 1.51, 95% CI: 1.07, 2.12, p = 0.019), SUB-DLN (HR: 1.72, 95% CI: 1.03, 2.86, p = 0.038), and SUB-O L(HR: 4.46, 95% CI: 1.39, 14.3, p = 0.012) were associated with OS. Multivariate analyses revealed that a higher N stage (HR: 1.23, 95% CI: 1.00, 1.50, p = 0.048), SUB-DLN (HR: 1.72, 95% CI: 1.02, 2.90, p = 0.043), and SUB-OL (HR: 3.72, 95% CI: 1.14, 12.16, p = 0.029) were associated with worse OS.ConclusionSubphrenic lymph node metastasis predicts poorer prognosis for NPC patients with metachronous metastasis; however, this needs validation by large prospective studies.

The output beam quality of high-power laser systems is limited by laser-induced thermal aberration of fused silica reflective optics. A numerical model for the simulation of thermal aberration was proposed and verified by the experimental results. Simulations on the thermal aberration of fused silica optics under 3~10 kW laser irradiation with laser beam diameters of 5 mm ~ 45 mm were carried out with the verified model. The simulation results showed that the peak-valley (PV) value of thermal aberration increases with increasing incident laser power under the same incident laser spot size and reduces with increasing incident laser spot size under the same incident laser power. There are the same PV values of thermal aberration under different incident power or power densities. An analytic formula of thermal aberration PV as a function of incident laser power and beam spot size was proposed. The analytic results are in good agreement with the simulations. With these conclusions, the thermal aberration of fused silica optics under high incident power and power density can be evaluated by that under low incident power and power density. It is helpful for the design of high-power laser systems to obtain reasonable output beam quality.

Background: Prostate cancer (PCa) is the fifth leading cause of death from cancer in men worldwide. Its treatment remains challenging due to the heterogeneity of the tumor, mainly because of the lack of effective and targeted prognostic markers at the system biology level.Methods: First, samples of PCa were retrieved from UCSC Xena data, and valid samples were obtained by consistent clustering and principal component analysis; next, key genes were analyzed for prognosis of PCa using WGCNA, MEGENA, and LASSO Cox regression model analysis, while key genes were screened based on disease-free survival (DFS) significance. Finally, TIMER data were selected to explore the relationship between genes and tumor immune infiltration, and GSCAlite was used to explore the small-molecule targeted drugs that act with them.Results: In this study, we used tumor subtype analysis and an energetic co-expression network algorithm of WGCNA and MEGENA to identify a signal dominated by the ROMO1 tag to predict PCa prognosis. Cox regression analysis of this signal was an independent influence, and the prognostic value of this biomarker was validated in the training set, the validated data itself, and external data, respectively. This biomarker correlates with tumor immune infiltration and has a high degree of infiltration, poor prognosis, and strong correlation with CD8+ T cells. Gene function annotation and other analyses also implied a potential molecular mechanism for ROMO1.Conclusions: In conclusion, our study suggests ROMO1 as a portal key prognostic gene for the diagnosis and prognosis of PCa. Moveover, we identify nutlin-3, fluorouracil, and other drugs as possible key drugs for diagnosis and prognosis, which provide new insights into the diagnosis and treatment of prostate cancer.

Background Antimony is widely used in industrial production. The general population may be exposed to long-term low-dose antimony, and there are no studies on antimony and depression symptoms. This study aims to explore the relationships between urinary antimony concentrations and depressive symptoms in adults. Methods We conducted a cross-sectional study using data from U.S. National Health and Nutrition Examination Survey (NHANES) 2007–2016 for urinary antimony (N = 8538). Depressive symptoms were assessed through Patient's Health Questionnaire (PHQ-9). In order to determine the relationships between urinary antimony concentrations and depressive symptoms, binary logistic regression model and restricted cubic spline were used. Dominance analysis was used to explore the relative importance between variables associated with depressive symptoms. Results There was a significant positive relationship between urinary antimony concentrations and depressive symptoms in the general population, and OR with 95% CI was 1.72 (1.15, 2.60). This relationship also occurred in participants without disease status, and OR with 95% CI was 2.05 (1.10, 3.82). After stratified gender, the urinary antimony concentrations were positively correlated with depressive symptoms in the highest tertiles of female participants, and OR with 95% CI was 1.74 (1.06, 2.86). After adjusted urinary lead, arsenic, cadmium, and mercury as covariates, the result was still statistically significant, and OR with 95% CI was 1.83 (1.23, 2.72). Restricted cubic spline showed a nonlinear positive relationship between urinary antimony and depressive symptoms. Based on the result of dominance analysis, the relative importance of urinary antimony concentration accounted for 3.58%. Conclusion This study indicated that urinary antimony was positively related to depressive symptoms, especially in female.

Although cancer immunotherapy with PD-(L)1 blockade is now routine treatment for patients with lung cancer, remarkably little is known about acquired resistance. We examined 1,201 patients with NSCLC treated with PD-(L)1 blockade to clinically characterize acquired resistance, finding it to be common (occurring in more than 60% of initial responders), with persistent but diminishing risk over time, and with distinct metastatic and survival patterns compared to primary resistance. To examine the molecular phenotype and potential mechanisms of acquired resistance, we performed whole transcriptome and exome tumor profiling in a subset of NSCLC patients (n=29) with acquired resistance. Systematic immunogenomic analysis revealed that tumors with acquired resistance generally had enriched signals of inflammation (including IFNγ signaling and inferred CD8+ T cells) and could be separated into IFNγ upregulated and stable subsets. IFNγ upregulated tumors had putative routes of resistance with signatures of dysfunctional interferon signaling and mutations in antigen presentation genes. Transcriptomic profiling of cancer cells from a murine model of acquired resistance to PD-(L)1 blockade also showed evidence of dysfunctional interferon signaling and acquired insensitivity to in vitro interferon gamma treatment. In summary, we characterized clinical and molecular features of acquired resistance to PD-(L)1 blockade in NSCLC and found evidence of ongoing but dysfunctional IFN response. The persistently inflamed, rather than excluded or deserted, tumor microenvironment of acquired resistance informs therapeutic strategies to effectively reprogram and reverse acquired resistance.

Deep reinforcement learning algorithms have made great progress in video games. However, there are still some problems, such as sample inefficiency and poor generalization. In this paper, we highlight that these problems are partially caused by the inability of convolutional neural networks (CNNs) to reason with the underlying relations between the objects in the image observations. Based on this point, we try to alleviate these problems in a more efficient and explainable way, including learning the representations of objects and reasoning the relations between them with a relation network (RN). Each pixel in the feature maps is treated as an object and our model explicitly learns the relations between object pairs. The relations are summarized through an attention mechanism and then fed into the downstream fully-connected layers. In the experiments, our model is compared with baseline models in three typical object based Atari games. Under the same hyperparameter settings, our model still achieves better sample efficiency and generalization capability. Further studies throw light on the impact of hyperparameters and verify the interpretability of the model.