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Background: Chronic rhinosinusitis (CRS) is a common inflammatory disease in otolaryngology, mainly manifested as nasal congestion, nasal discharge, facial pain/pressure, and smell disorder. CRS with nasal polyps (CRSwNP), an important phenotype of CRS, has a high recurrence rate even after receiving corticosteroids and/or functional endoscopic sinus surgery. In recent years, clinicians have focused on the application of biological agents in CRSwNP. However, it has not reached a consensus on the timing and selection of biologics for the treatment of CRS so far. Summary: We reviewed the previous studies of biologics in CRS and summarized the indications, contraindications, efficacy assessment, prognosis, and adverse effects of biologics. Also, we evaluated the treatment response and adverse reactions of dupilumab, omalizumab, and mepolizumab in the management of CRS and made recommendations. Key Messages: Dupilumab, omalizumab, and mepolizumab have been approved for the treatment of CRSwNP by the US Food and Drug Administration. Type 2 and eosinophilic inflammation, need for systemic steroids or contraindication to systemic steroids, significantly impaired quality of life, anosmia, and comorbid asthma are required for the use of biologics. Based on current evidence, dupilumab has the prominent advantage in improving quality of life and reducing the risk of comorbid asthma in CRSwNP among the approved monoclonal antibodies. Most patients tolerate biological agents well in general with few major or severe adverse effects. Biologics have provided more options for severe uncontrolled CRSwNP patients or patients who refuse to have surgery. In the future, more novel biologics will be assessed in high-quality clinical trials and applied clinically.

Introduction: In collaboration with the Department of Rheumatology, Allergy and Immunology, our study aims to review the outcomes of and propose an improved workflow for the management of patients with prior hypersensitivity reactions to iodinated contrast media (ICM). Method: Outpatients coming for contrast-enhanced computed tomography (CECT) were stratified into 3 categories (definite, unconfirmed and inaccurate) based on likelihood of their contrast hypersensitivity label. Patients could be offered a different ICM, receive the same ICM, or be referred to an allergist for further evaluation. There were 4 outcomes: (1) alternative ICM tolerated; (2) same ICM tolerated again; (3) patient developed a hypersensitivity reaction to either alternative or original ICM; and (4) CECT was deferred until assessment by an allergist. Comparison was made pre- and post-intervention to see if patient outcomes were improved. Results: There were 132 patients who made a total of 154 visits (90.3% had documented contrast hypersensitivity). Post-intervention, the number of visits postponed for premedication decreased (81.0% to 34.7%). There was a reduction in hypersensitivity reactions (from 42.9% to 14.3%). Of the 12 patients assessed by the allergist, 6 could continue using the same or alternative ICM, 4 were advised to abstain from further contrast administration and 2 were pending testing with a third agent. Conclusion: Active intervention by the radiologist can decrease the number of postponed, converted or cancelled CECT studies as well as reduce the number of adverse allergic-like events. Direct collaboration between radiologist and allergist for specific cases may be helpful in patients who will likely need future/repeated CECTs. Keywords: Corticosteroid, hypersensitivity, ICM, iodinated contrast media, premedication, skin testing

Purpose Deficiency of adenosine deaminase 2 (DADA2), an autosomal recessive autoinflammatory disorder caused by biallelic loss-of-function variants in adenosine deaminase 2 (ADA2), has not been systemically investigated in Chinese population yet. We aim to further characterize DADA2 cases in China. Methods A retrospective analysis of patients with DADA2 identified through whole exome sequencing (WES) at seventeen rheumatology centers across China was conducted. Clinical characteristics, laboratory findings, genotype, and treatment response were analyzed. Results Thirty patients with DADA2 were enrolled between January 2015 and December 2021. Adenosine deaminase 2 enzymatic activity was low in all tested cases to confirm pathogenicity. Median age of disease presentation was 4.3 years and the median age at diagnosis was 7.8 years. All but one patient presented during childhood and two subjects died from complications of their disease. The patients most commonly presented with systemic inflammation (92.9%), vasculitis (86.7%), and hypogammaglobinemia (73.3%) while one patient presented with bone marrow failure (BMF) with variable cytopenia. Twenty-three (76.7%) patients were treated with TNF inhibitors (TNFi), while two (6.7%) underwent hematopoietic stem cell transplantation (HSCT). They all achieved clinical remission. A total of thirty-nine ADA2 causative variants were identified, six of which were novel. Conclusion To establish early diagnosis and improve clinical outcomes, genetic screening and/or testing of ADA2 enzymatic activity should be performed in patients with suspected clinical features. TNFi is considered as first line treatment for those with vascular phenotypes. HSCT may be beneficial for those with hematological disease or in those who are refractory to TNFi.

Neuronal surface antibody-mediated autoimmune encephalitis (NSAE) occurs across a wide age range. However, few studies focused on the onset age and their related characteristics. We aimed to explore the age-dependent profile of NSAE. A total of 134 patients with a definite diagnosis of NSAE were retrospectively enrolled from 3 tertiary hospitals between July 2014 and August 2020. Demographic, clinical, therapeutic, and prognostic data were collected and compared between the late- (≥45) and younger-onset (

Seizure is one of the manifestations of central nervous system inflammatory demyelinating diseases, which mainly include multiple sclerosis (MS), aquaporin 4 antibody-positive neuromyelitis optica spectrum disorder (AQP4-NMOSD), and myelin oligodendrocyte glycoprotein antibody-associated disease (MOGAD). Acute symptomatic seizures secondary to MS/AQP4-NMOSD/MOGAD occur in the acute phase of the diseases, and are more frequent in MOGAD. In contrast, recurrent nonprovoked seizures, mainly attributed to autoimmune-associated epilepsy, occur in the nonacute phase of the diseases. Seizures in MS/AQP4-NMOSD/MOGAD mostly have a focal onset. MS patients with concomitant systemic infections, earlier onset, and greater disease activity are more likely to have seizures, whereas factors such as greater MS severity, the presence of status epilepticus, and cortical damage indicate a greater risk of developing epilepsy. In MOGAD, cerebral cortical encephalitis and acute disseminated encephalomyelitis (ADEM)-like phenotypes (predominately ADEM and multiphasic disseminated encephalomyelitis) indicate a greater seizure risk. Multiple relapses with ADEM-like phenotypes predict epilepsy in pediatrics with MOGAD. Pathophysiologically, acute symptomatic seizures in MS are associated with neuronal hyperexcitability secondary to inflammation and demyelination. Chronic epilepsy in MS is largely due to gliosis, neuronal dysfunction, and synaptic abnormalities. The mainstay of treatment for seizures secondary to MS/AQP4-NMOSD/MOGAD consists of immunotherapy along with antiseizure medications. This critical review discusses the most-updated evidence on epidemiology, clinical correlates, and inflammatory mechanisms underlying seizures and epilepsy in MS/AQP4-NMOSD/MOGAD. Treatment cautions including drug-drug interactions and the impact of treatments on the diseases are outlined. We also highlight pitfalls and challenges in managing such patients and future research perspectives to address unsolved questions.

Background: To evaluate the value of texture analysis (TA) of conventional magnetic resonance imaging (MRI) and diffusion-weighted imaging (DWI) in the differential diagnosis between sinonasal non-Hodgkin’s lymphoma (NHL) and squamous cell carcinoma (SCC).Methods: Twenty-one patients with sinonasal SCC and 15 patients with NHL were retrospectively enrolled. TAs were performed on T2-weighted image (T2WI), apparent diffusion coefficient (ADC) and contrast-enhanced T1-weighted image (T1WI). Texture parameters, including mean value, skewness, kurtosis, entropy and uniformity were obtained and compared between sinonasal SCC and NHL groups. Receiver operating characteristic (ROC) curves and logistic regression analyses were used to evaluate the diagnostic value and identify the independent TA parameters.Results: The mean value and entropy of ADC, and mean value of contrast-enhanced T1WI were significantly lower in the sinonasal NHL group than those in the SCC group (all P < 0.05). ROC analysis indicated that the entropy of ADC had the best diagnostic performance (AUC, 0.832; Sensitivity, 0.95; Specificity, 0.67; Cut-off value, 6.522). Logistic regression analysis showed that the entropy of ADC (P = 0.002, OR = 26.990) was the independent parameter for differentiating sinonasal NHL from SCC.Conclusion: TA parameters of conventional MRI and DWI, particularly the entropy value of ADC, might be useful in the differentiating diagnosis between sinonasal NHL and SCC.

Objectives: To evaluate the performance of texture analysis (TA) of diffusion kurtosis imaging (DKI) in differentiating malignant from benign sinonasal lesions, and its added value to the conventional imaging features. Methods: Fifty-eight patients with malignant and 40 patients with benign sinonasal lesions were retrospectively enrolled. Conventional CT and MRI features were reviewed. Texture parameters were obtained and compared between two groups. Multivariate logistic regression analysis was used to identify the most valuable variables. Receiver operating characteristic curves were performed to assess the differentiating performance of independent variables and their combination. Results: There were significant differences in tumor necrosis, bone erosion and soft tissue invasion between the two groups (all p < 0.05). There were significant differences in the 10th and entropy of Apparent diffusion coefficient map, the mean, 10th and entropy of D map, the mean and 90th of K map between the two groups (all p < 0.002). The bone erosion, entropy of D, and mean of K were independent variables associated with malignant tumors. Receiver operating characteristic analyses indicated that the combination of three features possessed better differentiating performance than bone erosion alone (p = 0.003). Conclusion: TA of DKI could supply incremental value to conventional imaging features for pre-operative differential diagnosis between benign and malignant sinonasal lesions. Advances in knowledge: The present study is the first to combine conventional imaging features and the TA of DKI in the differential diagnosis between benign and malignant sinonasal lesions. Our findings suggest that TA of DKI could supply incremental value to conventional imaging features.

Purpose To study the influence of sex, age and thyroid function indices on dual-energy computed tomography (DECT)-derived quantitative parameters of thyroid in patients with or without Hashimoto’s thyroiditis (HT). Material and methods A total of 198 consecutive patients who underwent DECT scan of neck due to unilateral thyroid lesions were retrospectively enrolled. Iodine concentration (IC), total iodine content (TIC) and volume of normal thyroid lobe were calculated. Influences of sex, age and thyroid function indices on DECT-derived parameters in overall study population, subgroup patients with, and those without HT were assessed using Mann–Whitney U test, Student’s T-test, and Spearman correlation analyses, respectively, as appropriate. Results HT group showed significantly lower IC and TIC, while higher volume than No-HT group (all p p = 0.047 and 0.010, respectively). There was no significant difference in any DECT-derived parameters between low (≤ 35 years) and high (> 35 years) age group in all three groups (all p > 0.05). TPOAb and TgAb correlated positively with IC and TIC, and negatively with volume in overall study population (all p p = 0.002 and 0.007, respectively). Conclusion DECT-derived parameters of thyroid differed significantly between patients with and without HT. Sex and thyroid function indices could affect the DECT-derived parameters. Aforementioned physiological factors should be considered when analyzing the DECT-derived parameters of thyroid.

Both sepsis and AKI are diseases of major concern in intensive care unit (ICU). This study aimed to evaluate the excess mortality attributable to sepsis for acute kidney injury (AKI). A propensity score-matched analysis on a multicenter prospective cohort study in 18 Chinese ICUs was performed. Propensity score was sequentially conducted to match AKI patients with and without sepsis on day 1, day 2, and day 3–5. The primary outcome was hospital death of AKI patients. A total of 2008 AKI patients (40.9%) were eligible for the study. Of the 1010 AKI patients with sepsis, 619 (61.3%) were matched to 619 AKI patients in whom sepsis did not develop during the screening period of the study. The hospital mortality rate of matched AKI patients with sepsis was 205 of 619 (33.1%) compared with 150 of 619 (24.0%) for their matched AKI controls without sepsis (p = 0.001). The attributable mortality of total sepsis for AKI patients was 9.1% (95% CI: 4.8–13.3%). Of the matched patients with sepsis, 328 (53.0%) diagnosed septic shock. The attributable mortality of septic shock for AKI was 16.2% (95% CI: 11.3–20.8%, p < 0.001). Further, the attributable mortality of sepsis for AKI was 1.4% (95% CI: 4.1–5.9%, p = 0.825). The attributable hospital mortality of total sepsis for AKI were 9.1%. Septic shock contributes to major excess mortality rate for AKI than sepsis. registration number ChiCTR-ECH-13003934

Purpose This study aimed to evaluate the attributable mortality of new-onset acute kidney injury (AKI). Methods The data in the present study were derived from a multi-center, prospective cohort study in China that was performed at 18 Chinese ICUs. A propensity-matched analysis was performed between matched patients with and without AKI selected from all eligible patients to estimate the attributable mortality of new-onset AKI. Results A total of 2872 critically ill adult patients were eligible. The incidence of new-onset AKI was 29.1% (n = 837). After propensity score matching, 788 patients with AKI were matched 1:1 with 788 controls (patients without AKI). Thirty-day mortality was significantly higher among the patients with AKI than among their matched controls (25.5% versus 17.4%, p p = 0.509) in 30-day mortality between patients with stage 1 AKI and their matched controls. The attributable mortality values of stage 2 and stage 3 AKI were 12.4% [95% confidence interval (CI) 2.6–21.8%, p = 0.013] and 16.1% (95% CI 8.2–23.8%, p p = 0.001), while no observable difference in 30-day mortality was identified between transient AKI patients and their matched non-AKI controls (p = 0.229). Conclusion The absolute excess 30-day mortality that is statistically attributable to new-onset AKI is substantial (8.1%) among general ICU patients. However, neither stage 1 AKI nor transient AKI increases 30-day mortality.

Using 95 countries’ panel data for the period 2000–2017, this research explores how GICT affects six types of ecological footprint (EF) with ERs as the interaction variables by concurrently testing the GICT-induced environmental Kuznets curve (EKC) hypothesis. Using a quantile regression (QR) that tests the effects of GICT on environment degradation varying across diverse quantiles of EF, we present the vital role that GICT plays in lessening cropland, forest area, and grazing land, while increasing consumption of built-up land. Additionally, the findings partially confirm the existence of an inverted U-shape EKC hypothesis of technologies about mitigation against climate change for cropland, forest area, and grazing land via consideration of non-market-based ER as the interaction term. GICT does not notably reduce carbon-absorption land usage, however, the interaction between GICT and non-market-based ER does.

ObjectiveWe aimed to evaluate the knowledge of the board members of the Zhejiang Association Against Epilepsy (ZAAE) regarding pregnancy of women with epilepsy (WWE), as well as their clinical practice and obstacles in the management of WWE.MethodsA cross-sectional survey was conducted among the board members of the ZAAE using a questionnaire based on the management guidelines for WWE during pregnancy in China. We recorded the demographic characteristics of the surveyed practitioners, the coincidence rate of each question, clinical practice, and the barriers encountered in managing WWE.ResultsThis survey showed that the average knowledge score of the surveyed practitioners was 71.02%, and the knowledge score of neurologists was higher than that of neurosurgeons. Knowledge regarding the following three aspects was relatively poor: whether WWE is associated with an increased risk of cesarean section and preterm delivery, the preferred analgesic drugs for WWE during delivery, and the time of postpartum blood concentration monitoring. After multiple linear regression analysis, the score of neurologists was correlated to the number of pregnant WWE treated each year. In addition, the biggest difficulty in the management of WWE during pregnancy is the lack of patient education and doctors training on pregnant epilepsy management.ConclusionOur study revealed the ZAAE board members' knowledge and management status of pregnant WWE. In addition, our study identified the biggest obstacle to the management of WWE during pregnancy, and emphasized the importance of training and practice of epilepsy knowledge during pregnancy for practitioners and the significance of interdisciplinary communication.

A new esterase gene, est6, was discovered in an activated sludge metagenomic library. The 729-bp gene encodes a 242-amino acid protein (designated Est6) with a molecular mass of 26.1 kDa. Est6 shared only a moderate identity to a putative hydrolase with the highest BLASTP analysis score. Most of the closely related proteins are uncharacterized and are predicted from genome sequencing data of microorganisms or metagenomic DNA sequences. The phylogenetic analysis of Est6 showed that the protein was assigned to family VI esterases/lipases. The catalytic triad of Est6 was predicted to be Ser135, Asp188, and His219, with Ser135 in a typically conserved pentapeptide (GFSQG) of family VI members, which was further confirmed by site-directed mutagenesis. The est6 gene was overexpressed successfully in its soluble form in Escherichia coli and then purified to its tag-free form and homogeneity by affinity chromatography. The purified Est6 in pH 8.0 buffer was active as a monomer. The optimal conditions for Est6 activity were at a temperature of 45 °C and pH of 8.0 when using p-nitrophenyl acetate as a substrate. The enzyme was stable over wide temperature and pH ranges, and it exhibited activity in the presence of organic solvents, metal cations, or detergents. Furthermore, the enzyme showed significant regioselectivity in the spectrophotometric analysis. In conclusion, Est6 might have the potential for applications in biotechnological processes.

Social Assistive Robotics is increasingly being used in care settings to provide psychosocial support and interventions for the elderly with cognitive impairments. Most of these social robots have provided timely stimuli to the elderly at home and in care centres, including keeping them active and boosting their mood. However, previous investigations have registered shortcomings in these robots, particularly in their ability to satisfy an essential human need: the need for companionship. Reports show that the elderly tend to lose interests in these social robots after the initial excitement as the novelty wears out and the monotonous familiarity becomes all too familiar. This paper presents our research facilitating conversations between a social humanoid robot, Nadine, and cognitively impaired elderly at a nursing home. We analysed the effectiveness of human–humanoid interactions between our robot and 14 elderly over 29 sessions. We used both objective tools (based on computer vision methods) and subjective tools (based on observational scales) to evaluate the recorded videos. Our findings showed that our subjects engaged positively with Nadine, suggesting that their interaction with the robot could improve their well-being by compensating for some of their emotional, cognitive, and psychosocial deficiencies. We detected emotions associated with cognitively impaired elderly during these interactions. This study could help understand the expectations of the elderly and the current limitations of Social Assistive Robots. Our research is aligned with all the ethical recommendations by the NTU Institutional Review Board.

Purpose: Deficiency of adenosine deaminase 2 (DADA2) is an autosomal recessive autoinflammatory disorder caused by biallelic loss-of-function mutations in ADA2, characterized by systemic inflammation, vasculitis, immunodeficiency, and/or hematologic abnormalities. Methods: A retrospective analysis of patients with DADA2 diagnosed by whole exome sequencing at 17 rheumatology centers across China was conducted. Clinical characteristics, laboratory findings, genotype and treatment responses were analyzed.Results Thirty patients with DADA2 were enrolled in this cohort between January 2015 and December 2021. Median age at onset was 4.3 years and the median age at diagnosis was 7.8 years. All but one patient presented during childhood and two subjects in the cohort died from DADA2-related complications. The patients presented with systemic inflammation (92.9%), vasculitis (86.7%), and hypogammaglobinemia (73.3%) while one patient with pure red cell aplasia (PRCA) and bone marrow failure (BMF) with variable cytopenia was observed in our cohort. Twenty-three (76.7%) patients received TNF inhibitors and all achieved clinical remission. Homozygous variants and compound heterozygous variants were identified in 5 and 25 patients, respective. Two patients received hematopoietic stem cell transplantation (HSCT), and both got remission. Among 39 unique variants in our cohort, six is novel.Conclusion: In order to establish the diagnosis early and prevent devastating clinical outcomes, genetic screening and/ or testing of adenosine deaminase enzymatic activity should be performed in patients with suspected clinical features. TNF inhibitors can be first line drug for patients with vasculitic DADA2. HSCT is an alternative choice for patients with refractory to TNF inhibitors or hematological disorders.

Our study investigated the effect of short-chain non-coding RNA 1251-5p on the movement and permeation of pulmonary carcinoma stem cells. LCSC in pulmonary carcinoma cells was determined and isolated by flow cytometry. After cell transfection, qRT-PCR and immunoblotting measured the level of MiR-1251-5p, MiR-650, SLC34A2, Oct4 and CD133. Spherometric mensuration was used to assess sphericity formation situation. Transwell analyzed the movement and permeation of cells, detected the relationship among MiR-1251-5p, MiR-650 and SLC34A2 by fluorescein enzyme report gene, and the results were verified by RIP and RNA pull-down detection methods. Knock-down of MiR-1251-5p can enhance the stem cell-like characteristics of LCC, promote cell migration and invasion, upregulate the level of MiR-650, Oct4 and CD133, and downregulate the level of SLC34A2, while MiR-650 inhibitor can restore the effect of the knock-down on the hyperplasia, movement and permeation of LCSC cells. Si-Mir-1251-5p promoted stem cell like characteristics of pulmonary carcinoma cell lineage H1299 and downregulated the expression of Oct4 and CD133, and upregulated the level of SLC34A2. SLC34A2 expression was negatively correlated with MiR-650 expression and positively correlated with MiR-1251-5p in LCSC cellular tissues. MiR-1251-5p regulates LCC stem cell-like state, and inhibits the movement and permeation of pulmonary carcinoma cells via MiR-650/SLC34A2 axis.

ObjectivesThe current study evaluates the performance of dual-energy computed tomography (DECT) derived extracellular volume (ECV) fraction based on dual-layer spectral detector CT for diagnosing cervical lymph nodes (LNs) metastasis from papillary thyroid cancer (PTC) and compares it with the value of ECV derived from conventional single-energy CT (SECT).MethodsOne hundred and fifty-seven cervical LNs (81 non-metastatic and 76 metastatic) were recruited. Among them, 59 cervical LNs (27 non-metastatic and 32 metastatic) were affected by cervical root artifact on the contrast-enhanced CT images in the arterial phase. Both the SECT-derived ECV fraction (ECVS) and the DECT-derived ECV fraction (ECVD) were calculated. A Pearson correlation coefficient and a Bland–Altman analysis were performed to evaluate the correlations between ECVD and ECVS. Receiver operator characteristic curves analysis and the Delong method were performed to assess and compare the diagnostic performance.ResultsECVD correlated significantly with ECVS (r = 0.925; p D (42.41% vs 22.53%, p S (39.18% vs 25.45%, p D of 36.45% as the cut-off value, optimal diagnostic performance could be achieved (AUC = 0.813), which was comparable with that of ECVS (cut-off value = 34.99%; AUC = 0.793) (p = 0.265). For LNs affected by cervical root artifact, ECVD also showed favorable efficiency (AUC = 0.756), which was also comparable with that of ECVS (AUC = 0.716) (p = 0.244).ConclusionsECVD showed a significant correlation with ECVS. Compared with ECVS, ECVD showed comparable performance in diagnosing metastatic cervical LNs in PTC patients, even though the LNs were affected by cervical root artifacts on arterial phase CT.

Background Existing clinical studies supported the potential efficacy of mesenchymal stromal cells as well as derived exosomes in the treatment of COVID-19. We aimed to explore the safety and efficiency of aerosol inhalation of the exosomes derived from human adipose-derived MSCs (haMSC-Exos) in patients with COVID-19. Methods The MEXCOVID trial is a phase 2a single-arm, open-labelled, interventional trial and patients were enrolled in Jinyintan Hospital, Wuhan, China. Eligible 7 patients were assigned to receive the daily dose of haMSCs-Exos (2.0 × 108 nano vesicles) for consecutively 5 days. The primary outcomes included the incidence of prespecified inhalation-associated events and serious adverse events. We also observed the demographic data, clinical characteristics, laboratory results including lymphocyte count, levels of D-dimer and IL-6 as well as chest imaging. Results Seven severe COVID-19 related pneumonia patients (4 males and 3 females) were enrolled and received nebulized haMSC-Exos. The median age was 57 year (interquartile range (IQR), 43 year to 70 year). The median time from onset of symptoms to hospital admission and administration of nebulized haMSC-Exos was 30 days (IQR, 15 days to 40 days) and 54 d (IQR, 34 d to 69 d), respectively. All COVID-19 patients tolerated the haMSC-Exos nebulization well, with no evidence of prespecified adverse events or clinical instability during the nebulization or during the immediate post-nebulization period. All patients presented a slight increase of serum lymphocyte counts (median as 1.61 × 109/L vs. 1.78 × 109/L). Different degrees of resolution of pulmonary lesions after aerosol inhalation of haMSC-Exos were observed among all patients, more obviously in 4 of 7 patients. Conclusions Our trial shows that a consecutive 5 days inhalation dose of clinical grade haMSC-Exos up to a total amount of 2.0 × 109 nano vesicles was feasible and well tolerated in seven COVID-19 patients, with no evidence of prespecified adverse events, immediate clinical instability, or dose-relevant toxicity at any of the doses tested. This safety profile is seemingly followed by CT imaging improvement within 7 days. Further trials will have to confirm the long-term safety or efficacy in larger population. Trial Registration: MEXCOVID, NCT04276987.

Using a new panel quantile regression approach, this research explores how investor attention and policy uncertainties affect conditional return distributions for 126 cross-border U.S. trading single-country exchange traded funds (ETFs). We find that economic, fiscal, and monetary policy uncertainties negatively impact most of the ETF return quantiles, implying that a non-linear relationship exists, but trade policy uncertainty has asymmetric impacts on current returns that are salient positive in the following period. Therefore, considering four policy uncertainties allows us to completely analyze a single-country ETF market, thus providing valuable insights for ETF portfolio investors, hedge trading, and policymakers.

Bi2Sr2CaCu2O8+δ(BSCCO) single crystals are promising for high-temperature superconducting electronic devices with ultimate performance. Recently, tailoring superconductivity in ultra-thin BSCCO locally has received wide attention and interest. In this work, we focus on controlling the superconductivity of the uppermost CuO2double layer of the BSCCO crystal. Gold electrodes are deposited onto the freshly cleaved BSCCO surface by a high-vacuum in situ evaporation technique at room temperature, and then surface Josephson junctions (SJJs) between the two outermost superconducting CuO2double layers are fabricated as a probe to evaluate the superconductivity of the uppermost double layer. We find that the junction transition temperature Tc′ as well as its critical current density jcdepend systematically and reproducibly on the deposition rate of the gold electrode. The electric properties of the SJJs, spanning the range from completely degraded to almost as good as the intrinsic Josephson junctions inside the bulk, systematically reveal the evolutionary process of superconductivity of the uppermost BSCCO layer, extending the range for practical applications.

This research crucially investigates COVID-19 variables’ impacts on the changing distributions of travel and leisure industry returns across 65 countries via a quantile regression model that uses daily data from December 2019 to May 2020 to provide early evidences from a panel of countries. We find that the change rate in COVID-19 deaths exerts more substantial negative effects on industry returns at majority quantiles than does the impact from the number of confirmed cases. The latter number only saliently and negatively influences the lowest return quantiles, revealing a nonlinear effect of confirmed cases. The study identifies a V-shape correlation between the number of cases recovered and travel and leisure industry returns (i.e. a negative impact at the lower quantiles, but a positive impact at higher quantiles) across return quantiles. This likely denotes that confirmed cases grow exponentially and that their effect may overwhelm the impact of the number of recovered cases. Lastly, this study presents a positive correlation between government response stringency index and returns.

To evaluate the therapeutic effectiveness and cost-efficiency of first-line immunotherapies on neuronal surface antibody-mediated autoimmune encephalitis (AE) based on a real-world observational study in China.Our study retrospectively collected the clinical and paraclinical data of patients with definite neuronal surface antibody-mediated AE between July 2014 and July 2020. Regular follow-up was performed after administering standard regimens of first-line immunotherapies, including intravenous methylprednisolone (IVMP) and / or intravenous immunoglobulin (IVIG). Therapeutic effectiveness was reflected by modified Rankin Scale scores. The health resource utilization and direct medical costs were extracted to analyze the cost-efficiency.Among the 78 eligible patients, 48 (61.5%) were males with a median age of 40 years. More than half (56, 71.8%) were treated with combination therapy, with the rest receiving IVMP and IVIG monotherapy (both of 11, 14.1%). Related objective variables, i.e., sex, onset age, disease course, onset symptoms, antibody types, abnormal paraclinical results, disease severity, and the health insurance, showed insignificant differences on the selection of therapy. Each therapy showed similar short-term (4-week) and long-term (1-year) therapeutic effects. Yet the single or combination of IVIG had a slightly better effectiveness but higher cost than the monotherapy of IVMP.The combination of IVMP and IVIG was used more frequently than either alone, which may be associated with neurologist's personal experience and patient's wishes. Though with similar therapeutic effectiveness, the use of IVMP alone might be a better choice with a better cost-efficiency.

Allergic rhinitis (AR) is a nasal inflammatory disease resulting from a complex interplay between genetic and environmental factors. The association between Toll-like receptor (TLR) signaling pathway and environmental factors in AR pathogenesis remains to be explored. This study aims to assess the genetic association of AR with single nucleotide polymorphisms (SNPs) in TLR signaling pathway, and investigate the roles of gene-gene and gene-environment interactions in AR.A total of 452 AR patients and 495 healthy controls from eastern China were enrolled in this hospital-based case-control study. We evaluated putatively functional genetic polymorphisms inIn the single-locus analysis, two SNPs inThe genetic polymorphisms of

Dof(DNA binding with one finger), a unique class of transcription factors in plants, play an important role in seed development, tissue differentiation, and metabolic regulation. To identify the number and function of Dof gene family members in Panax ginseng, this study identified the members of Dof gene family in P. ginseng and systematically analyzed their structures, evolution, functional differentiation, expression patterns, and interactions using bioinformatics methods at the transcriptome level. At the same time, the association analysis of Dof genes from P. ginseng with key enzyme genes for ginsenoside synthesis was carried out to screen the candidate PgDof genes involved in the regulation of ginsenoside biosynthesis. The results showed that there were 54 genes belonging to the Dof gene family in P. ginseng from Jilin. All PgDof genes had Zf-Dof conserved motifs, implying that they were evolutionarily conserved and could be divided into five groups. Expression pattern analysis confirmed that the expression of PgDof gene family members in different tissues, different year-old P. ginseng, and different farm varieties varied significantly. Simultaneously, as revealed byquot;gene-saponin contentquot; andquot;gene-genequot; linkage analysis, an important candidate PgDof14-1 gene involved in the regulation of ginsenoside biosynthesis was obtained. From the established genetic transformation system of this gene in the hairy roots of P. ginseng, a positive hairy root clone was determined. This study has laid a theoretical foundation for the study of Dof gene family in P. ginseng.

The choice of friction interface has always been a controversial topic in hip arthroplasty. Although the metal-on-metal (MoM) interface has gradually faded out of our vision, its revision is a clinical difficulty. Adverse reactions to metal debris (ARMD) is the most common indication for MoM hip arthroplasty revision, and the clinical results of hip arthroplasty due to ARMD are not satisfactory. At present, the indications and suggestions for revision of ARMD are not uniform. In this article, the clinical diagnosis, indications of revision, risk factors of prognosis, intraoperative suggestions and reasons for revision of ARMD were summarized. This article briefly introduces the diagnosis and treatment strategies and precautions of hip arthroplasty due to ARMD, in order to provide reference for such patients in clinical practice.

BackgroundRecently, the paraneoplastic neurologic syndrome (PNS) diagnostic criteria have received a major update with a new score system over the past 16 years. We aimed to evaluate the diagnostic performance and clinical utility in China.MethodsAn eligible cohort of 113 Chinese patients diagnosed with PNSs from the Second Affiliated Hospital School of Medicine Zhejiang University and published data were enrolled retrospectively. Data including clinical phenotype, antibody type, the presence of cancer, and duration of follow-up were reviewed and re-evaluated to classify the diagnostic levels for the 2004 and 2021 PNS criteria. The performances of these 2 criteria were compared. The critical parameters of antibody and cancer for the updated criteria were further explored.ResultsThe cohort consisted of 69 males and 44 females with a median age of 60 years. Limbic encephalitis (23, 20.4%), anti-Hu antibody (32, 28.3%), and small-cell lung cancer (32, 28.3%) were the most common clinical phenotype, detected antibody, and concomitant cancer, respectively. A total of 97 (85.8%) patients were diagnosed with definite PNS according to the 2004 criteria: only 42.3% (41/97) fulfilled the 2021 criteria, while the remaining 40, 14, and 2 re-diagnosed with probable PNS, possible PNS, and non-PNS. The requirement of cancers consistent with antibody and phenotype increased the specificity and thus greatly enhanced the accuracy of the 2021 criteria.ConclusionThe updated criteria for PNS emphasized the consistency between cancer phenotype and antibody and showed a better diagnostic value. A better diagnostic yield could benefit disease management.

Additional file 1: Table S1. Baseline characteristics of included patients with cervical cancer. Table S2. The histological types of included cervical adenocarcinoma. Figure S1. RNA expression of COPA in cell lines based on HPA database. (A) The cell lines ordered by human tissues and organ; (B) The cell lines ordered by descending RNA expression order. Figure S2. HPA (The Human Protein Atlas) analyses for the COPA predicted that the protein was detected in nucleoplasm, cytosol and Golgi apparatus and was predicted to be secreted. Figure S3. Histograms showing the distributions of ages of the 140 patients with cervical cancer in the IHC analysis. Figure S4. The positions of COPA plotted in the volcano plots of cervical cancer (AC and SCC) vs. healthy controls.

This research fills the gap in the tourism literature on the impacts of country stability—including political, financial, and economic—on tourism development (i.e., international tourist arrivals, international tourism revenues, and travel and leisure sector returns). To account for possible asymmetric and nonlinear relationships among variables, we apply a new method of moment quantile regression, by using panel data from 106 countries spanning the period 2006–2017. From a global perspective, the empirical results indicate that higher country stability generally leads to higher tourism development, while there is no salient influence of financial stability on travel and leisure sector returns. This suggests that the effects of country risk ratings are mostly nonlinear across different tourism development quantiles. Additionally, different components of risk rating scores have diverse impacts on tourism development. The findings mean that policy makers should consider their tourism condition when setting country stability strategies.

Background Localization of small pulmonary nodules is an inevitable challenge for the thoracic surgeon. This study aimed to investigate the accuracy of three‐dimensional (3D) printing technology for localizing small pulmonary nodules, especially ground‐glass nodules (GGNs). Methods This study enrolled patients with peripheral small pulmonary nodules (≤ 2 cm) who required preoperative localization. In the comparison period, patients underwent both computed tomography‐guided (CT‐G) and 3D‐printing template guided (3D‐G) localization to compare the accuracies of the two methods. In the testing period, the 3D‐printing technique was implemented alone. The 3D‐printing physical navigational template was designed based on data from perioperative CT images. Clinical data, imaging data, surgical data, and evaluation index were collected for further analysis. The learning curve of the 3D‐printing localization technique was assessed using cumulative sum (CUSUM) analysis and multiple linear regression analysis. Results In the comparison period (n = 14), the success rates of CT‐G and 3D‐G were 100% and 92.9% (P = 0.31), respectively; in the testing period (n = 23), the success rate of 3D‐G was 95.6%. The localization times of CT‐G, 3D‐G (comparison), and 3D‐G (testing) were 23.6 ± 5.3, 19.3 ± 6.8, and 9.8 ± 4.6 minutes, respectively. The CUSUM learning curve was modeled using the equation: Y = 0.48X2 − 0.013X − 0.454 (R2 = 0.89). The learning curve was composed of two phases, phase 1 (the initial 20 patients) and phase 2 (the remaining 17 patients). Conclusions 3D printing localization has adequate accuracy and is a feasible and accessible strategy for use in localizing small pulmonary nodules, especially in right upper lobe. The use of this technique could facilitate lung nodule localization prior to surgery., Localization of small pulmonary nodules is an inevitable challenge for the thoracic surgeon. This study demonstrated that the 3D printing localization technique is a feasible and accessible strategy to localize non‐palpable pulmonary nodules.

Sequential invasive-noninvasive ventilation (NIV) improves the outcomes of patients with respiratory failure caused by acute exacerbation of chronic obstructive pulmonary disease (AECOPD); however, there is no clear consensus on the optimal timing of the switch to sequential invasive-NIV in these patients. In the present study, a potential role for the modified Glasgow Coma Scale (GCS) score to guide sequential weaning was investigated. Patients with AECOPD and respiratory failure were prospectively recruited from three study centers (Wenling Hospital Affiliated to Wenzhou Medical University, the First Affiliated Hospital of Wenzhou Medical University and Changsha Central Hospital) between January 1st 2016 and December 31st 2018. Patients were randomly assigned to group A and B, with the switching point for sequential weaning strategy in the two groups being a modified GCS score ≥13 and 10 points, respectively. Each group included 240 patients. Baseline demographic characteristics were comparable in the two groups. The duration of invasive mechanical ventilation (IMV) in group A was significantly shorter than that in group B. However, there were no significant between-group differences with respect to the incidence of re-intubation, ventilator-associated pneumonia, in-hospital mortality or the length of hospital stay. Use of a modified GCS score ≥13 as the switching point for sequential invasive-NIV may help decrease the duration of IMV in patients with AECOPD and respiratory failure.

To investigate the value of radiomics analysis of dual-energy computed tomography (DECT)–derived iodine maps for preoperative diagnosing cervical lymph nodes (LNs) metastasis in patients with papillary thyroid cancer (PTC). Two hundred and fifty-five LNs (143 non-metastatic and 112 metastatic) were enrolled and allocated to training and validation sets (7:3 ratio). Radiomics features were extracted from arterial and venous phase iodine maps, respectively. Radiomics signature was constructed based on reproducible features using the least absolute shrinkage and selection operator (LASSO) logistic regression algorithm with 10-fold cross-validation. Logistic regression modeling was employed to build models based on CT image features (model 1), radiomics signature (model 2), and the combined (model 3). A nomogram was plotted for the combined model and decision curve analysis was applied for clinical use. Diagnostic performance was assessed and compared. Internal validation was performed on an independent set containing 78 LNs. Model 3 showed optimal diagnostic performance in both training (AUC = 0.933) and validation set (AUC = 0.895), followed by model 2 (training set, AUC = 0.910; validation set, AUC = 0.847). Both these two models outperformed model 1 in both training (AUC = 0.763) (p

This study aimed to explore the role of miR-146b-3p in acute respiratory distress syndrome in septic mice. Ten mice were randomly selected as normal group (n = 10, without any treatment) and 60 septic mice with acute respiratory distress syndrome were divided into model group (n = 10, without any treatment), negative control (NC) mimic group (n = 10, injected with NC mimic), miR-146b-3p mimic group (n = 10, injected with miR-146b-3p mimic), si-NC group (n = 10, injected with PI3Kγ siRNA NC), si-PI3Kγ group (n = 10, injected with PI3Kγ silencing plasmid), and miR-146b-3p mimic + oe-PI3Kγ group (n = 10, injected with miR-146b-3p mimic + PI3Kγ overexpression plasmid). We found that miR-146b-3p negatively regulated PI3Kγ. Compared with normal group, model mice had decreased expression of miR-146b-3p, increased expressions of PI3Kγ, p-AKT, ASC, NLRP3 and Caspase-1 proteins, higher W/D ratio, and more serum IL-1β and IL-18 content (all P

The existing tourism- and happiness-related literature commonly investigates whether a happy destination does in fact render tourists happy and how tourist arrivals affect residents’ happiness. This research thus first explores whether the host country and Twitter happiness indices influence tourism development in an international framework (i.e. tourist arrivals, tourism revenues, and travel and leisure sector returns). To account for intricate correlations among variables, the study employs a quantile regression approach on panel data from 119 countries spanning 2006–2017. Evidences find that most host country happiness indices and macroeconomic factors show salient, nonlinear, and asymmetric impacts across both tourist arrival and tourism revenue quantiles in concurrent and subsequent periods, except for European country results. Moreover, Twitter happiness index strongly affects travel and leisure sector returns, but has no impact on tourist arrivals as well as tourism revenues, implying the importance of social media happiness on said returns.

Nitrogen and sulfur co-doped porous nanocarbon (ZIF-C-N-S) catalyst was successfully synthesized derived from ZIF-8 and thiourea precursors. The electrochemical measurements indicate that the as-obtained ZIF-C-N-S catalyst exhibits higher electrocatalytic activity for oxygen reduction reaction (ORR) in alkaline electrolyte and superior durability-longer than commercial Pt/C catalyst. The enhancment of electrocatalytic activity mainly be come from the open pore structure, large specific surface area as well as the synergistic effect resulted from the co-doping of N and S atoms. In addition, the ZIF-C-N-S catalyst is also used as the air cathode catalyst in the microbial fuel cell (MFC) device. The maximum power density and stable output voltage of ZIF-C-N-S based MFC are 1315 mW/m2 and 0.48 V, respectively, which is better than that of Pt/C based MFC.

The foundation pit construction risk of subway stations is affected by various uncertain factors, which cannot be analyzed quantitatively by current methods. A synthetic evaluation index system for foundation pit construction risk of subway stations is established by analyzing the factors that influence subway station construction. Based on the hierarchy of these factors, a model of three-stage fuzzy synthetic evaluation is proposed, an analytic hierarchy process is used to determine the weight of each stage factor, the fuzzy sets method is used to determine the membership function, and risk ranking is carried out. The proposed method is applied to a subway station construction of the Qingdao Subway Line No. 3 Project. The simulation results show that the method is reasonable and that it should be practical and helpful for other similar projects.

Background House dust mite (HDM)‐induced allergic rhinitis (AR) is a highly prevalent disease with bothersome symptoms. Genetic variants of the Hippo pathway genes play a critical role in the respiratory disease. However, no study has reported associations between variants of the Hippo pathway genes and HDM‐induced AR risk. Methods Forty‐three key genes in the Hippo pathway were selected from the Kyoto Encyclopedia of Genes and Genomes (KEGG), Reactome pathway database, and previous reported studies. A case‐control study of 222 cases and 237 controls was performed to assess the associations between 121 genetic variants in these genes and HDM‐induced AR risk. DNeasy Blood & Tissues Kits were used for extracting genomic DNA from the venous blood and Infinium Asian Screening Array BeadChips for performing genotyping. A logistic regression model was applied to evaluate the effects of variants on HDM‐induced AR risk. The false discovery rate (FDR) method was utilized to correct for multiple testing. The receiver operating characteristic (ROC) curve was plotted to obtain the cut‐off value of total IgE for the diagnosis of HDM‐induced AR. Histone modification and transcription factor binding sites were visualized by UCSC genome browser. Moreover, expression qualitative trait loci (eQTL) analysis was obtained from Genotype‐Tissue Expression (GTEx) database. Results We found that rs754466 in DLG5 was significantly associated with a decreased HDM‐induced AR risk after FDR correction (adjusted odds ratio [OR] = 0.52, 95% confidence interval [CI] = 0.36–0.74, p = 3.25 × 10−4, P FDR = 3.93 × 10−2). The rs754466 A allele reduced the risk of HDM‐induced AR in the subgroup of moderate/severe total nasal symptom score (TNSS). Furthermore, rs754466 was associated with a high mRNA expression of DLG5. Additionally, histone modification and transcription factor binding sites were rich in the region containing rs754466. Conclusion Our findings indicated that rs754466 in DLG5 decreased the susceptibility to HDM‐induced AR.