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I review the existing literature in international trade that uses Indonesian firm-level data, particularly the Survei Tahunan Perusahaan Industri Pengolahan (Annual Manufacturing Survey) compiled b...

Remifentanil (RFT), extensively used for general anesthesia, is a synthetic ultra-short-acting opioid used as an anti-inflammatory oxidant to alleviate a plethora of diseases. This study was designed to determine whether RFT would provide protective effects on sepsis-induced intestinal injury.RFT was used to incubate the lipopolysaccharide (LPS)-treated IEC-6 cells for determining the role of RFT in sepsis-induced intestinal injury and the underlying mechanism. The determination of cell viability and inflammation of LPS-treated IEC-6 cells influenced by RFT was conducted by Cell counting Kit-8 (CCK-8), RT-qPCR, and western blot, while the detection of LDH, diamine oxidase (DAO), and intestinal-type fatty acid binding proteins (I-FABP) was conducted for determining the intestinal cytotoxicity in these cells. The apoptosis of these cells was detected by TUNEL, with autophagy-related protein expression measured by western blot to confirm whether autophagy was activated. Finally, the aforementioned assays were conducted again after 3-Methyladenine (3-MA), an autophagy inhibitor, was used on these cells to investigate whether RFT exerted its effects on LPS-treated IEC-6 cells via modulation of autophagy.RFT alleviates LPS-induced IEC-6 cell inflammation, cytotoxicity and apoptosis, and autophagy-related proteins were expressed at higher levels when RFT was used on these cells. Nevertheless, further treatment of 3-MA weakened the restorative impacts of RFT on the inflammation, cytotoxicity and apoptosis of these cells.To conclude, this paper is the first to present evidence that RFT attenuates sepsis-induced intestinal injury by inducing autophagy, which will provide instructions for the future investigations into the use of RFT in treatment of intestinal injury.

It was to explore the clinical efficacy and safety of epidermal growth factor receptor-tyrosine kinase inhibitor (EGFR-TKI) targeted drugs combined with hyaluronic acid-gadolinium sesquioxide-nanoparticles (HA-Gd2O3-NPs) in non-small cell lung cancer (NSCLC). In this study, 70 patients with stage IV EGFR mutant NSCLC diagnosed in the First Affiliated Hospital of Jinzhou Medical University were selected. They were randomly divided into the combined group (35 cases) and the control group (35 cases). HA-Gd2O3-NPs were prepared by hydrothermal polymerization, and combined with EGFR-TKI in the clinical treatment of NSCLC. The results showed that HA-Gd2O3-NPs were spherical with a uniform particle size of about 124 nm. The NSCLC survival rate of the combined group was 37.2 ± 5.3% under 6 Gy X-ray irradiation, and that of the control group was 98.4 ± 12.6% under 6 Gy X-ray irradiation. The total effective rate of the control group (20%) was significantly lower than that of the study group (42.86%) (P

Type 2 diabetes mellitus (T2DM) is known as a complex genetic disease characterized by genetic and environmental factors. The imbalanced intestinal flora and intestinal mucosal barrier are considered to be related to T2DM. Curcumin has been proved to affect the progression of T2DM. T2DM animal was established by low-dose streptozotocin intraperitoneal injection combined with high-fat diet (HFD) feeding. Hematoxylin and eosin (HE) staining and transfer electron microscopy (TEM) were used to observe morphological changes of intestinal tissues of T2DM rats. Insulin and glucose tolerance tests were performed to investigate the influence of curcumin on blood glucose. Curcumin significantly improved the intestinal integrity, hyperglycemia and insulin resistance in diabetic rats. The metabolic endotoxemia induced by HFD in diabetic rats was inhibited remarkably. Curcumin reversed gut microbiota dysbiosis in diabetic rats caused by HFD. We demonstrated that curcumin could protect intestinal mucosal barrier, improve insulin resistance and reduce blood glucose in diabetic rats. This study might provide experimental evidence for the prevention and treatment in T2DM.

Sepsis-induced myocardial dysfunction (SIMD) is ubiquitous in septic shock patients and is associated with high morbidity and mortality rates. Heat shock protein 22 (Hsp22), which belongs to the small HSP family of proteins, is involved in several biological functions. However, the function of Hsp22 in lipopolysaccharide (LPS)-induced myocardial injury is not yet established. This study was aimed at investigating the underlying mechanistic aspects of Hsp22 in myocardial injury induced by LPS. In this study, following the random assignment of male C57BL/6 mice into control, LPS-treated, and LPS + Hsp22 treated groups, relevant echocardiograms and staining were performed to scrutinize the cardiac pathology. Plausible mechanisms were proposed based on the findings of the enzyme-linked immunosorbent assay and Western blotting assay. A protective role of Hsp22 against LPS-induced myocardial injury emerged, as evidenced from decreased levels of creatinine kinase-MB (CK-MB), lactate dehydrogenase (LDH), and enhanced cardiac function. The post-LPS administration-caused spike in inflammatory cytokines (IL-1β, IL-6, TNF-α and NLRP3) was attenuated by the Hsp22 pre-treatment. In addition, superoxide dismutase (SOD) activity and B-cell lymphoma-2 (Bcl2) levels were augmented by Hsp22 treatment resulting in lowering of LPS-induced oxidative stress and cardiomyocyte apoptosis. In summary, the suppression of LPS-induced myocardial injury by Hsp22 overexpression via targeting of inflammation, oxidative stress, and apoptosis in cardiomyocytes paves the way for this protein to be employed in the therapy of SIMD.

Immune response imbalance and cardiac dysfunction caused by sepsis are the main reasons for death in sepsis. This study aimed to confirm the expression and diagnostic possibility of microRNA-381-3p (miR-381-3p) and its mechanism in sepsis. Quantitative real-time PCR (qRT-PCR) and receiver operating characteristic (ROC) were used to reveal the levels and clinical significance of miR-381-3p. Pearson correlation was conducted to provide the correlations between miR-381-3p and several indexes of sepsis. The H9c2 cell models were constructed by lipopolysaccharide (LPS), and cecal ligation and puncture (CLP) was applied to establish the Sprague-Dawley (SD) rat models. Cell Counting Kit-8 (CCK-8) and flow cytometry were the methods to detect the cell viability and death rate of H9c2. Enzyme-linked immunosorbent assay (ELISA) was performed to evaluate the concentration of inflammatory cytokines. The target gene of miR-381-3p was validated via the luciferase report system. The low expression of miR-381-3p was found in the serum of patients with sepsis. The lessened miR-381-3p could be a marker in the discrimination of sepsis patients. Overexpression of miR-381-3p could repress the mRNA expression of HMGB1, inhibit the cell apoptosis and inflammatory response, and motivate the viability of sepsis cells. At the same time, enhanced miR-381-3p promoted the inhibition of inflammation and cardiac dysfunction in the rat model of sepsis. Collectively, reduced levels of serum miR-381-3p can be used as an index to detect sepsis patients. MiR-381-3p restored the inflammatory response and myocardial dysfunction caused by sepsis via HMGB1.

ABSTRCTThe α-fetoprotein (AFP) and soluble intercellular adhesion molecule-1 (sICAM-1) have certain diagnostic value, but their potential value in prognosis prediction, especially immunotherapy response prediction, remains unclear in liver cancer. Through the tumour-free survival (TFS) and overall survival (OS) rates analyses of serum AFP and sICAM-1 levels in 87 patients with primary hepatocellular carcinoma (HCC), the patients whose AFP and sICAM-1 levels were normal (AFP < 20 μg/L or sICAM-1 < 1000 μg/L) before surgery or recovered to normal after surgery exhibited a lower tumour recurrence rate and better OS than patients with elevated serum levels of the two markers. Combined analysis showed that patients with synchronously elevated levels of AFP and sICAM-1 showed the lowest TFS and OS. In addition, the RNA-seq data and clinical information of The Cancer Genome Atlas Liver Hepatocellular Carcinoma were collected to analyse the predictive values of AFP and ICAM-1 in the diagnosis, prognosis and immunotherapy of HCC. The results indicated that the combined application of the two indicators had higher accuracy in both the diagnosis and prognostic prediction of HCC by receiver operating characteristic curves. AFP and ICAM-1 were significantly correlated with multiple immune cells in HCC samples but not in normal samples. The patients with low expression of the two indicators were most likely to benefit from the immune checkpoint blockade therapy. In conclusion, AFP and ICAM-1 play vital roles in the diagnosis, prognostic prediction, and immunotherapy of HCC, suggesting that they are considered as prognostic predictors in clinical practice.

Dexmedetomidine (DEX) has been reported to attenuate cecal ligation perforation (CLP)-stimulated acute lung injury (ALI) by downregulating HMGB1 and RAGE. This study aimed to further investigate the specific mechanisms of RAGE and its potential-related mechanisms of DEX on ALI models in vitro and in vivo. The in vitro and in vivo ALI models were established by lipopolysaccharide treatment in MLE-12 cells and CLP in mice, respectively. The effect of DEX on pathological alteration was investigated by HE staining. Thereafter, the myeloperoxidase (MPO) activity and inflammatory cytokine levels were respectively detected to assess the lung injury of mice using commercial kits. The expression levels of HMGB1, RAGE, NF-κB, and pyroptosis-related molecules were detected by RT-qPCR and Western blot. HE staining showed that lung injury, increased inflammatory cell infiltration, and lung permeability was found in the ALI mice, and DEX treatment significantly attenuated lung tissue damage induced by CLP. The MPO activity and inflammatory cytokines (TNF-α, IL-1β, and NLRP3) levels were also significantly reduced after DEX treatment compared with those in the ALI mice. Moreover, DEX activated the HMGB1/RAGE/NF-κB pathway and upregulated the pyroptosis-related proteins. However, the protective DEX effect was impaired by RAGE overexpression in ALI mice and MLE-12 cells. Additionally, DEX treatment significantly suppressed HMGB1 translocation from the nucleus region to the cytoplasm, and this effect was reversed by RAGE overexpression. These findings suggested that DEX may be a useful ALI treatment, and the protective effects on ALI mice may be through the inhibition of HMGB1/RAGE/NF-κB pathway and cell pyroptosis., Graphical abstractDexmedetomidine (DEX) has protective effects on acute lung injury (ALI) in vitro and in vivo. The possible mechanisms may be closely associated with inflammatory response, caspase-1-mediated cell pyroptosis, and high-mobility group protein 1 (HMGB1)/receptor for advanced glycation end products (RAGE)/nuclear factor-κB pathway. Moreover, DEX could promote the HMGB1 translocation from the cytoplasm to the nucleus in lipopolysaccharide-activated MLE-12 cells, whereas the action of RAGE overexpression was opposite.

Temporal lobe epilepsy (TLE) often occurs in childhood and is the most common type of epilepsy. Studies have confirmed that long non-coding RNAs (lncRNAs) can affect the progression of neurological diseases. This study explored the expression level of lncRNA TUG1 in TLE children and its clinical significance and investigated its role in hippocampal neurons. 86 healthy individuals and 88 TLE children were recruited. The expressions of lncRNA TUG1 and miR-199a-3p in serum were detected by qRT-PCR. Hippocampal neurons were treated with non-Mg2+ to establish TLE cell model. MTT assay and flow cytometry assay was used to detect the effect of lncRNA TUG1 on the proliferation and apoptosis of hippocampal neurons. A dual-luciferase reporter assay was done to confirm the target relationship. The expression of lncRNA TUG1 was increased in TLE children compared with the control group. The diagnostic potential was reflected by the receiver operator characteristic (ROC) curve, with the AUC of 0.915 at the cutoff value of 1.256. Elevated levels of TUG1 were detected in TLE cell models, and TUG1 knockout could enhance cell activity and inhibit cell apoptosis. MiR-199a-3p was the target of TUG1. Clinically, the serum miR-199a-3p levels showed a negative association with TUG1. LncRNA TUG1 may be a biomarker of TLE diagnosis in children, and can regulate hippocampal neuron cell activity and apoptosis via sponging miR-199a-3p.

Glaucoma, characterized with progressive degeneration of retinal ganglion cells (RGCs), is the second frequently leading cause of sight loss in the word after cataract. Baicalin plays a protective role in age-related macular degeneration, retinopathy of prematurity, branch retinal vein occlusion, and ischemia-induced neurodegeneration in the retina. The present study aimed to investigate the role of baicalin in glaucoma. RGCs were stimulated with N-methyl-D-aspartate (NMDA) to mimic the in vitro model of glaucoma. A mouse model of glaucoma induced by chronic elevated intraocular pressure was also established. The apoptosis, oxidative stress, and autophagy of RGCs were detected by flow cytometry analysis, 2,7-dichlorodihydrofluorescein diacetate staining, and Western blotting, respectively. Retinal pathological changes were exhibited by hemotoxylin and eosin staining. Baicalin restrained the NMDA-induced cell apoptosis, autophagy, and oxidative stress of RGCs by activating the PI3K/AKT signaling in vitro. The elevated intraocular pressure-induced pathological changes in retinas of glaucoma mice were attenuated by baicalin. Moreover, the number of RGCs was significantly decreased in glaucoma mice, and then increased by baicalin treatment. Baicalin also inhibited autophagy and activated PI3K/AKT signaling in vivo. In conclusion, baicalin suppresses glaucoma pathogenesis by regulating the PI3K/AKT signaling in vitro and in vivo.

Acute kidney injury (AKI), a common complication of sepsis, is characterized by a rapid loss of renal excretory function. A variety of etiologies and pathophysiological processes may contribute to AKI. Previously, mitogen-activated protein kinase 1 (MAPK1) was reported to regulate cellular processes in various sepsis-associated diseases. The current study aimed to further explore the biological function and regulatory mechanism of MAPK1 in sepsis-induced AKI. In our study, MAPK1 exhibited high expression in the serum of AKI patients. Functionally, knockdown of MAPK1 suppressed inflammatory response, cell apoptosis in response of lipopolysaccharide (LPS) induction in HK-2 cells. Moreover, MAPK1 deficiency alleviated renal inflammation, renal dysfunction, and renal injury in vivo. Mechanistically, MAPK1 could activate the downstream p38/NF-κB pathway. Moreover, long noncoding RNA potassium voltage-gated channel subfamily Q member 1 opposite strand/antisense transcript 1 (KCNQ1OT1) was identified to serve as a competing endogenous RNA for miR-212-3p to regulate MAPK1. Finally, rescue assays indicated that the inhibitory effect of KCNQ1OT1 knockdown on inflammatory response, cell apoptosis, and p38/NF-κB pathway was reversed by MAPK1 overexpression in HK-2 cells. In conclusion, KCNQ1OT1 aggravates acute kidney injury by activating p38/NF-κB pathway via miR-212-3p/MAPK1 axis in sepsis. Therefore, KCNQ1OT may serve as a potential biomarker for the prognosis and diagnosis of AKI patients.

Vaccine hesitancy (VH) has emerged as a recognized threaten to contain the COVID-19 pandemic. Historically, low vaccine acceptance rates had been described among patients with rheumatic diseases (RMDs). The study objective was to determine COVID-19 VH among Mexican outpatients with RMDs and validate the COVID-19 VH questionnaire. This cross-sectional study was developed in three steps. Step 1 consisted of translation/cultural adaptation of the Oxford-COVID-19-VH questionnaire. Step 2 consisted of pilot testing and questionnaire feasibility, content, construct and criterion validity, reliability (internal consistency and temporal stability) and questionnaire sensitivity to change. Step 3 consisted of VH phenomenon quantification in patients from two metropolitan tertiary-care-level centers. Step 1 followed ISPOR-task-force recommendations. Patients who participated in step 2 (n = 50 for pilot testing/feasibility and n = 208 for questionnaire validation [91 in test–retest and 70 in questionnaire-sensitivity to change]) and step 3 (n = 600) were representative outpatients with RMDs. The seven-item COVID-19 VH questionnaire was found feasible, valid (experts’ agreement ≥80%; a 1-factor structure accounted for 60.73% of the total variance; rho = 0.156, p = .025 between COVID-19 VH questionnaire and score from the Spanish version of the Vaccine Hesitancy Scale; and lower questionnaire scores in patients who reported 5 years-previous influenza vaccination), reliable (Cronbach’s ɑ = 0.889, intra-class correlation coefficient = 0.933 and 95% confidence interval = 0.898–0.956) and sensitive to change (effect size = 1.17 and 0.86, respectively, in patients who decreased [n = 34] and increased [n = 31] questionnaire-score after intervention). VH phenomenon was 35.5%. VH phenomenon was present in a substantial number of Mexican patients with RMDs. The COVID-19 VH questionnaire showed good psychometric properties to assess COVID-19 VH in our population.

The five-year survival rate for pancreatic ductal adenocarcinoma (PDAC) has remained a dismal 9% for approximately 40 years with an urgent need for novel therapeutic interventions. ONC201 is the founding member of the imipridone class, comprised of orally bioavailable small molecules that have shown efficacy in multiple tumor types both in animal models and in Phase I/II clinical trials. ONC201 is a potent inducer of the tumor necrosis factor related apoptosis inducing ligand (TRAIL) pathway. TRAIL is an innate immune mechanism which induces programmed cell death of cancer cells. We observed that PDAC cells upregulated ATF4, CHOP, and DR5 after treatment with ONC201. This occurred in cell lines that are susceptible to ONC201-induced apoptosis and in ones that are not. In response to ONC201, PDAC cells downregulated anti-apoptotic proteins including c-FLIP, BclXL, XIAP, cIAP1, and survivin. We hypothesized that TRAIL receptor agonists might induce selective, synergistic apoptosis in pancreatic cancer cell lines treated with ONC201. We screened 7 pancreatic cancer cell lines and found synergy with ONC201 and rhTRAIL or the novel TRAIL receptor agonist TLY012 in 6 of the 7 cell lines tested. In vivo experiments using BxPC3 and HPAFII xenograft models showed that the combination of ONC201 plus TLY012 significantly delays tumor growth as compared to controls. Immunohistochemical analysis of the tumors after three doses of the combination showed significantly increased cleavage of caspase 3 in vivo as compared to controls. Taken together, the preclinical efficacy of ONC201 and TLY012 represents a novel therapeutic option for further testing in pancreatic cancer patients. This combination showed marked efficacy in tumor cells that are both sensitive and resistant to the pro-apoptotic effects of ONC201, providing rationale to further investigate the combination of ONC201 plus TLY012 in patients with pancreatic cancer.

The incidence and mortality of breast cancer rank first among all types of female tumors. To improve patients’ prognosis with advanced breast cancer, new and more effective targets still need to be explored and identified. Tetraspanin 1 (TSPAN1) is highly expressed in several cancers and affects the progression of these tumors. However, there are few studies focused on its role in breast cancer. Previous study showed that TSPAN1 promoted epithelial-mesenchymal transition (EMT) and metastasis, and whether TSPAN1 could promote breast cancer via regulating EMT needs further study. In this study, we found high TSPAN1 expression in breast cancer tumor samples and cell lines which was confirmed by bioinformation analysis. The ablation of TSPAN1 suppressed the growth, and motility of breast cancer cells. We further found that TSPAN1 affected the EMT and mediated the PI3K/Akt pathway in breast cancer cells. In addition, TSPAN1 depletion suppressed tumor growth of breast cancer in mice. In summary, we thought TSPAN1 suppressed growth and motility of breast cancer via mediating EMT and PI3K/AKT pathway, and could serve as a potential target for treatment of breast cancer.

Epidemiologic data regarding the risk of Guillain-Barré syndrome (GBS) following herpes zoster (HZ) are limited. We conducted a self-controlled case series analysis using two large national data sources to evaluate the risk of GBS following HZ among U.S. adults. We analyzed medical claims from the IBM® MarketScan® Commercial Claims and Encounters (persons 18-64 years during 2010-2018) and Centers for Medicare and Medicaid Services Medicare (persons ≥65 years during 2014-2018) databases. HZ cases were defined as persons with an outpatient claim with a primary or secondary ICD-9 or ICD-10 diagnostic code for HZ. GBS cases were defined as persons with an inpatient claim with a principle diagnostic code for GBS and an associated procedural code. We compared the rates of GBS following HZ in the 1-42-day risk window versus primary (100-365-day) or secondary (43-99-day) control windows. We identified 489,516 persons 18-64 years of age and 650,229 persons ≥65 years of age with HZ, among whom 11 and 41, respectively, developed GBS 1-365 days following HZ. The risk of GBS following HZ was increased during the risk window as compared to the primary control window for both groups, with a rate ratio of 6.3 (95% CI, 1.8-21.9) for those 18-64 years and 4.1 (95% CI, 1.9-8.7) for those ≥65 years. This study provides new and methodologically rigorous epidemiologic support for an association between HZ and GBS, and useful context regarding the benefits versus potential risks of zoster vaccination.

Web-based technology has proven itself indispensable in education, especially in distance education and in developing countries. Technological advances and the Covid-19 pandemic have forced higher education institutions to be innovative in delivering education in their countries. This paper seeks to demonstrate the role and value of e-portfolios as an alternative teaching and learning tool in distance education and the online environment, especially in developing countries. A systematic review of peer-reviewed academic studies of e-portfolios between 2010 and 2020 was conducted. A total of 18 papers were selected according to the inclusion criteria. The review shows that the use of e-portfolios is still a relatively new trend in developing countries. The study also revealed that e-portfolios can infuse important skills such as self-directed learning, critical thinking and lifelong learning. These results have the potential to help institutions to creatively design appropriate support tools and strategies alongside the implementation of e-portfolios in their contexts.

Our study investigates the interlink between liquidity, corporate governance and firm value with the adoption of meta-analysis. The final sample consists of 428 studies extracted from 55 papers, covering 632,196 firm-year observations in a worldwide scope. The diversity in data is believed to reduce possible homogeneity due to regional or time period concentration. Using random-effects model, it is reported that both illiquidity factors (Spread and Amihud illiquidity) can significantly worsen the performance of a firm, while the corporate governance – firm value connection is significantly positive via three out of four factors (Corporate governance index, Board size and Institutional ownership). Besides studying the overall relationship direction, the paper also looks into its heterogeneity. The existence of heterogeneity is confirmed in all liquidity – firm value and governance – firm value relationship. The running of meta-regression indicates that both illiquidity factors are significantly moderated by most of the examined paper characteristics, whilst only two out of four corporate governance indicators (Corporate governance index and Institutional ownership) are significantly altered.

This article aims to contextualise the inherent resilience of Central Eurasian states through the exploration of their particular history. The main purpose is to ground the ideas of resilience and capacity building in the context of the geography and ecology of Central Eurasia thus confronting the current views of the need for making these communities resilient by borrowing European, Western or global ‘best practice’ in order to achieve stability and development. This paper offers an overview of the history of the region to bring into focus the ‘local’ Central Eurasian milieu. The sophisticated tapestry of understanding, action and strategies developed over centuries has made this region resilient in the face of unpredictability caused by natural and manmade events. This paper seeks to locate how the region has consistently overcome obstacles in its long history of inhabiting a disparate space. We apply the term intercalation here to describe the emergence of a collective identity from strongly interacting ingredients that represents the inherent resilience of the region. Consequently, the focus is on the ways in which communities within the region connect, cooperate and build nodes of interaction to achieve prosperity and development.

The verifications of current-state opacity (CSO) and initial-state opacity (ISO) in discrete event systems (DESs) both suffer from the curse of dimensionality, as these issues were proved to be PSPACE-complete. Hence, how to reduce the state space is crucial. In this paper, we investigate CSO and ISO in modular DESs, which consist of several individual components. Necessary and sufficient conditions of CSO and ISO for modular DESs are derived under the assumption that all synchronous events are observable by each components of modular DESs. Moreover, we prove that the initial state estimator of modular system is isomorphic to the synchronous composition of initial state estimators for individual components. These results offer us the opportunity to reduce the complexity in verifying the opacity of modular DESs.

Efficient bandwidth utilization is significant in new communication systems where secondary users can be used besides of primary users considering interference issues and idle state of primary users. Using secondary users as relays to transmit their own signals in addition to the primary signals can be applied for more reliability of the system where opportunistic relay selection can significantly enhance the performance of the system. The best-condition secondary user is selected as the optimum relay for retransmission of primary/secondary signal. Outage probability is analyzed in this paper based on decode and forward techniques in secondary users while the closed-form statement for outage probability is provided and verified by numerical evaluations.

Technological advances in tea production are critical to meet global demands for tea consumption. To illuminate differences in the scientific and commercial relevance of research programs between major tea-related research organizations around the world, we conducted a bibliometric analysis comparing the scientific outputs, including peer-reviewed publications and patents, of six major research organizations published between January 01, 2008 and July 11, 2020. For this competitive ranking analysis, we examined a number of papers, research topics, academic influence, capacity for development, capacity for collaboration, and capacity for technological innovation. Among the six research organizations, Anhui Agricultural University (in China) had the most publications, while the Chinese Academy of Agricultural Sciences, Tea Research Institute showed a higher capacity for development. The Council for Scientific and Industrial Research (in India) and the University of Shizuoka (Japan) both showed high academic influence, while the University of Shizuoka, Tea Research Association Tocklai and National Agriculture and Food Research Organization (Japan) showed a high capacity for collaboration. The Chinese Academy of Agricultural Sciences, Tea Research Institute applied for the most patents, while the Council for Scientific and Industrial Research applied for the most international patents.

The goal of this paper is to evaluate the informational content of sentiment extracted from news articles about the state of the economy. We propose a fine-grained aspect-based sentiment analysis that has two main characteristics: 1) we consider only the text in the article that is semantically dependent on a term of interest (aspect-based) and, 2) assign a sentiment score to each word based on a dictionary that we develop for applications in economics and finance (fine-grained). Our data set includes six large US newspapers, for a total of over 6.6 million articles and 4.2 billion words. Our findings suggest that several measures of economic sentiment track closely business cycle fluctuations and that they are relevant predictors for four major macroeconomic variables. We find that there are significant improvements in forecasting when sentiment is considered along with macroeconomic factors. In addition, we also find that sentiment matters to explains the tails of the probability distribution across several macroeconomic variables., Comment: 46 pages, 11 figures, to be published in Journal of Business & Economic Statistics

Most patients with psoriasis present with localized mild-to-moderate disease. In this case, the application of topical treatments in the first-line setting is recommended in most cases. Among different topical options, the fixed-dose combination of betamethasone dipropionate (BD) and vitamin D analogue (Cal) aerosol foam (Enstilar®, Leo Pharma) is approved as first-line topical therapy for the treatment of psoriasis in USA and the EU, due to its high efficacy and its favorable administration scheme. The PSO-LONG was the first trial to report on the long-term efficacy and safety of the Cal/DB foam treatment for the proactive management of psoriasis and now, the indications of Cal/BD foam included its use in the psoriasis maintenance treatment. However, the precise role of this treatment and the potential therapeutic schemes in the long-term management of psoriasis need further clarification. This Position Paper, authored by a group of Italian Expert Dermatologists, critically discusses the long-term management of psoriasis with Cal/BD foam in clinical practice. In particular, the biological rationale in the proactive treatment with Cal/BD foam and current evidence regarding this therapeutic approach are presented, along with its application also in patients with moderate-to-severe disease, difficult-to-treat lesions, or within combination regimens. In addition, strategies to improve adherence to long-term treatment of psoriasis are discussed,.

This study explores urban forestry as a maintenance practice capable of enhancing more-than-human commons in the city. Focusing on the places associated with tree care, the methodology takes as a case study the Tokyo Metropolitan Parks, conducting quantitative and qualitative analysis through the means of immersive field work and questionnaires, to reveal how urban forestry practices materialize within the parks. Regarding the spatial relations between humans and/or non-humans with resources, different Urban Forestry Elements (UFE) have been found, as well as their collection in groups within the parks forming Urban Forestry Assemblages (UFA). The paper creates a comprehensive framework that reveals these places for urban forestry as important beacons for urban commoning.

In this paper, I empirically study the effect of chain affiliation on product variety and price in the movie theater industry. Using longitudinal data on Korean movie theaters, I find that movie variety in a theater increases by 3.2-5.5 percent after the theater joins a chain. Admission price, however, does not change after chain affiliation, implying that consumers benefit from the organizational form change. These results are consistent with the growing dominance of chain-affiliated theaters in recent decades. The results also suggest that the regulatory authorities should carefully examine the trade-off between increase in market power and efficiency gains when evaluating the implications of chain affiliation.

In computational and applied statistics, it is of great interest to get fast and accurate calculation for the distributions of the quadratic forms of Gaussian random variables. This paper presents a novel approximation strategy that contains two developments. First, we propose a faster numerical procedure in computing the moments of the quadratic forms. Second, we establish a general moment-matching framework for distribution approximation, which covers existing approximation methods for the distributions of the quadratic forms of Gaussian variables. Under this framework, a novel moment-ratio method (MR) is proposed to match the ratio of skewness and kurtosis based on the gamma distribution. Our extensive simulations show that 1) MR is almost as accurate as the exact distribution calculation and is much more efficient; 2) comparing with existing approximation methods, MR significantly improves the accuracy of approximating far right tail probabilities. The proposed method has wide applications. For example, it is a better choice than existing methods for facilitating hypothesis testing in big data analysis, where efficient and accurate calculation of very small $p$-values is desired. An R package Qapprox that implements related methods is available on CRAN.

A recent survey of Europe’s highway infrastructure has concluded that almost half of Europe’s bridges are nearing the end of their design live. Work in the wider Structural Health Monitoring sector is aiming to develop reliable and cost-effective methods for verifying condition, remaining service life and safety of ageing structures. Most bridge condition assessment methods are based on deflection, acceleration or strain measurements. This paper looks at the possibility of using rotation measurements as a main parameter to identify damage. This study looks at numerical analyses of a moving point load on a one-dimensional bridge model to provide the theoretical basis of the proposed damage detection method. It is shown that when local damage occurs, even when it is remote from a sensor location, it results in an increase in the magnitude of rotation measurements. This study looks at how best to exploit this fact for damage detection. A number of damage scenarios, sensor locations, and load arrangements are investigated in this study and their influence on the ability of the algorithm to detect damage are reported.

This is an Accepted Manuscript of an article published by Taylor & Francis Group in International journal of electronics on Published online: 30 Dec 2021, available online at: https://www.tandfonline.com/doi/abs/10.1080/00207217.2021.2007544 Increasing the voltage gain by means of Z-source network will provide some features such as low voltage stress of semiconductor devices, low duty cycle of the switch and low reverse recovery problem of output diode that leads to improve the converter performance and efficiency. The proposed converter in this paper employs a Z-source network with coupled inductors integrated with flyback converter to make it appropriate for high step-up applications. One magnetic element is used in this converter, which is its main advantage over previously introduced Z-source converters. Steady state analysis and operation principles of the proposed converter in continuous conduction mode that leads to low current ripple, and low conductive losses for semiconductor devices due to decreasing the RMS currents are presented. In order to verify the theoretical analysis, experimental results of a prototype are provided. This converter’s high voltage conversion ratio will result in 300 V output from 20 V input voltage source for 100 W output power

Introduction A cell surface bile acid receptor TGR5 can be considered a promising target for the treatment of various metabolic diseases. The TGR5 receptor is expressed in various tissues, including the liver, kidney, intestine, and adrenal glands, causing its effect in each tissue to differ. A major role for TGR5 is to maintain blood sugar levels. Also, TGR5 is postulated to contribute to an increase in energy expenditure. These benefits make it a potential candidate for the treatment of type 2 diabetes, obesity, and other metabolic diseases. Area covered This paper highlights recent advances in the development of potent steroidal and non-steroidal TGR5 agonists and the peer-reviewed scientific articles that have led to understanding the structure-activity relationship for TGR5 agonists (2012-2020). The review also discusses the clinical progress made by some TGR5 agonists over the past eight years. Expert opinion Preclinical studies have suggested a key role for the TGR5 receptor in GLP-1 secretion and have shown promising outcomes such as weight loss, anti-inflammatory, anti-diabetic effects. Along with the evaluation of semisynthetic derivatives, synthetic compounds can also be considered as a possible avenue for the discovery of novel TGR5 agonists. Currently, few TGR5 agonists have reached the clinical trial stage, and, likely, we will soon discover a novel TGR5 modulator with fewer adverse effects. In silico studies can be performed with these scaffolds ranging from steroidal to heterocyclic rings to discover selective and safe TGR5 agonists.

Non-invasive brain stimulation techniques such as repetitive transcranial magnetic stimulation (rTMS) offer a promising alternative to psychotherapeutic and pharmacological treatments for depression. This paper aims to present a practical guide for its clinical implementation based on evidence from the literature as well as on the experience of a group of leading German experts in the field.The current evidence base for the use of rTMS in depression was examined via review of the literature. From the evidence and from clinical experience, recommendations for the use of rTMS in clinical practice were derived. All members of the of the German Society for Brain Stimulation in Psychiatry and all members of the sections Clinical Brain Stimulation and Experimental Brain Stimulation of the German Society for Psychiatry, Psychotherapy, Psychosomatics and Mental Health were invited to participate in a poll on whether they consent with the recommendations.Among rTMS experts, a high consensus rate could be identified for clinical practice concerning the setting and the technical parameters of rTMS treatment in depression, indications and contra-indications, the relation of rTMS to other antidepressive treatment modalities and the frequency and management of side effects.

OBJECTIVE The concept of 'patient-centered care' was touted as a pillar of good clinical practice and endorsed by the US Institute of Medicine in a seminal 2001 publication. We explore the extent to which differing medical specialties have engaged with the concept over the last 20 years and how and why this attention has varied among a sample of medical specialties since 2001. METHODS Reference to patient-centered care in the medical literature for selected specialties was used as a proxy for clinical application of patient-centered care in those disciplines. We undertook a statistical analysis and historical review of the medical literature that references the concept of patient-centered care in pediatrics, obstetrics and gynecology (OB-GYN), orthopedics, radiology, dermatology, and neurosurgery. We analyzed the extent to which the literature referencing patient-centered care has changed for the six disciplines since first mentioned in the Institute of Medicine 2001 publication. We measured changes over time in reference to patient-centered care in the medical literature for six diverse medical specialties. RESULTS The six disciplines differed significantly in reference to patient-centered care when comparing publications between the disciplines (p < 0.001). Pediatrics showed the most extensive reference to the concept followed by OB-GYN. In contrast, patient-centered care was hardly mentioned in dermatology and neurosurgery, nor orthopedics or radiology. When correcting for the number of papers published in the different fields, reference to patient-centered care is ~18X more common in pediatrics than in neurosurgery. CONCLUSION Uptake, attention and applicability of the principles of patient-centered care have varied over the last 20 years. Differences among specialties appear to reflect true differences in patient centricities in the disciplines, with higher uptake in specialties that are person-oriented rather than technique-oriented. Greater engagement with patient-centered care correlates strongly with the number of female physicians in each field.

Employing Bourdieu’s practice theory, this paper explores factors that influence corporate executives’ behaviour towards corporate governance regulation. Drawing insights from a weak institutional environment (Nigeria) and relying on a qualitative research methodology (semi-structured interviews with 31 executives), this research uncovers how nine nuanced situational and cultural field factors determine executives’ regulatory response to the severity of punishment, the certainty of penalties, and the cost–benefit compliance considerations. The study further explains how sequential rationalisation between the severity and certainty of punishment contributes to the regulatory apathy that executives exhibit. Theoretically, this study demonstrates how practice theory components (habitus, capital, and field) blend to establish executives’ regulatory practice.

Introduction: The implementation of technology in the field of epileptology has traditionally focused on its use for diagnosis and treatment and has, unsurprisingly, been capital-intensive, making it therefore mainly implementable in advanced high-income countries. Because of technological innovations over the past 20 years there has been almost a paradigm shift, particularly in access to and the potential for implementing relevant technology in lesser developed environments. Nearly 80% of people living with epilepsy live in low and middle-income countries. Areas covered: The challenge and the purpose of this paper is to discuss how technology can be implemented into lesser-resourced contexts not only cost-effectively but in a cost-saving way while also building capacity and thus sustainability. Expert opinion: The rate of technological advancement presents the risk of progressive widening of the technology and care gaps between advanced and lesser developed regions. Implementing technology is both about finding relevant appropriate technologies for the individual contexts of a diverse range of countries but also about repurposing low-tech technologies for application in epilepsy care in these areas. Finally exciting advances such as autonomous driving, digital twinning and robotic surgery will likely transform epilepsy care in several lower-resourced settings in the next 5- 10 years.

The malignant neoplastic cell is characterized by its diverse metabolic changes. It occurs in order to maintain the high rate of proliferation. The possibility of new pharmacological targets has inserted tumor metabolism as a target for recent research, emphasizing the enzymatic activity of thiamin. This review aims to elucidate the behavior of thiamin against tumor development. This is a systematic review in which studies indexed in Pubmed, Scopus, SciELO and BVS were searched using the descriptors (Thiamin OR Vitamin B1) AND (Cancer OR Malignant neoplasia) AND (Tumor metabolism). Title and abstract were read. Duplicates, literary reviews, books, conference abstracts, editorials, and papers published prior to 2010 were eliminated. 23 records were included in this review. Low doses of thiamin have been shown to be enough to stimulate tumor growth. Another population studies has shown evidence of tumor regression after correction of vitamin B1 deficiency. There is an open path for the development of new research to better assess the influence of thiamin on cancer cells. Once the connections between thiamin and the metabolism of cancer cells are fully established, new opportunities for therapeutic intervention and dietary modification will appear to reduce the progression of the disease in patients with cancer.

Alberto Migliore,1 Gianfranco Gigliucci,1 Lyudmila Alekseeva,2 Raveendhara R Bannuru,3 Tomasz Blicharski,4 Demirhan Diracoglu,5 Athanasios Georgiadis,6 Hesham Hamoud,7 Natalia Martusevich,8 Marco Matucci Cerinic,9 Jan Perduk,10 Imre Szerb,11 Tomáš Tr&ccaron;,12 Xavier Chevalier13 1Rheumatology Unit - San Pietro Fatebenefratelli Hospital, Rome, Italy; 2Department of Metabolic Diseases of Bone and Joints, V.A. Nasonova Research Institute of Rheumatology, Moscow, Russian Federation; 3Center for Treatment Comparison and Integrative Analysis (CTCIA) at Tufts Medical Center, Boston, MA, USA; 4Lubelskie Centrum Diagnostyczne, &Sacute;widnik, Poland; 5Department of Physical Medicine and Rehabilitation, Istanbul University, Istanbul, Turkey; 6Department of Rheumatology, University of Ioannina, Ioannina, Greece; 7Department of Rheumatology Al Azhar University, Cairo, Egypt; 8Department of Rheumatology, Belarusian State Medical University, Minsk, Belarus; 9Division of Rheumatology, University of Florence, Florence, Italy; 10Department of Musculoskeletal Medicine and Sports, Hospital Košice -Šaca, Kosice Saca, Slovakia; 11Semmelweis University, Department of Traumatology Uzsoki Hospital, Department of Orthopaedics&Traumatology FIFA Medical Centre of Excellence Uzsoki u.29– 41, Budapest, Hungary; 12Department of Orthopaedic Surgery, Charles University and Motol University Hospital, Prague, Czech Republic; 13Rheumatology Division, Henri-Mondor Hospital, Créteil, FranceCorrespondence: Alberto MiglioreRheumatology Unit - San Pietro Fatebenefratelli Hospital, Rome, ItalyEmail reumafbf@libero.itAbstract: Osteoarthritis (OA) is a significant cause of disability. Considering the increasing diffusion of the viscosupplementation (VS) with hyaluronic acid (HA), the International Symposium Intra Articular Treatment (ISIAT) appointed a Technical Expert Panel (TEP) to identify the criteria for successful VS with a specific HA in OA; this through a systematic literature review (SLR), performed following the PRISMA guidelines interrogating Medline, Embase, Cochrane Library, Cumulative Index to Nursing and Allied Health Literature (CINAHL), Grey Matters and American College of Rheumatology (ACR/EULAR) databases and the opinion of international experts. The research included only studies on adults and humans without limitations of language or time of publication. Researchers extracted both quantitative and qualitative data from each study. Mixed Methods Appraisal Tool (MMAT) was used to perform quality analysis for the level of evidence. The SLR retrieved 385 papers, 25 of which were suitable for the analysis. The TEP focused on the different formulations of the product Sinovial® [HA 0.8%, HA 1.6%, HA 2%, 800– 1200 kDa, HA 3.2% (1400– 2100 kDa/65– 110 kDa)]. The choice was due to the vast amount of evidence available. The TEP weighed the evidence in two rounds of a Delphi survey; the results, and any disagreement, were discussed in a final session. Three domains were considered: 1) the patients’ characteristics associated with the best results; 2) the contraindications and the conditions linked to increased risk of failure; 3) the clinical conditions in which VS is considered appropriate. The TEP concluded that VS with HA is safe and effective in the treatment of knee and hip OA of grades I to III and that it is possible to undertake VS in other situations (eg grade IV Kellgren-Lawrence – KL); a comprehensive examination of the patient should be performed before the procedure.Keywords: appropriateness, osteoarthritis, personalized medicine, viscosupplementation

This paper explores how university staff in Denmark, Germany, and England perceived higher education (HE) policy as impacting the experience of being a student in their respective countries. While,...

Health is becoming an increasingly important aspect of built environment design. We aim to bridge the gap between existing knowledge in medicine and its potential applications. This paper tests the extent to which Active Urbanism can facilitate gaining and maintaining bone mass widely across the population through encouraging serendipitous high impact exercise. Based on a review of successful high impact exercise programs, we run a biokinetics experiment in a laboratory measuring ground reaction forces to match those based on field sociological pilot studies in the urban environment. Considering data collected, Active Urbanism can increase the bone density of an average child not previously involved in sport by 12% in 10 years, and that of an average adult by 2.8% in 10 years. This new parameter has the potential to support infrastructure and landscape designers to optimize their plans and will need further examination by communities of these practices.

This research uses the theoretical framework of CALL normalisation developed by Bax (2003) and Chambers and Bax (2006) to offer a systematic review (Gough et al., 2012) of the uses and spread of data-driven learning (DDL) and corpora in language learning and teaching across five major CALL-related journals during the 2011–2015 period. DDL research represented 4.2% of all published papers on CALL during this time frame. The main focus of research was found to be the use of concordancing and collocations when developing university students’ writing skills. Contrary to previous research, access to technology was not identified as an impeding factor for normalisation. Syllabus integration and a lack of contribution from language teachers other than researchers emerged as threats to the normalisation of corpora use. Further theorisation is needed if DDL and corpora are to expand their influence on mainstream second language education.

Automated steering technology offers significant benefits to the safety and efficiency of vehicles, but desire to keep the human driver in the loop requires better understanding of the interaction between driver and vehicle. An existing noncooperative-game-theoretic framework for modelling such interaction is revisited in this paper, leading to the development of two alternative driver steering control models. Both models bears Nash-equilibrium properties but involve different assumptions about driver steering control behaviour. A simulation study is performed to demonstrate the difference between the two driver models in terms of their simulated driver steering angles and vehicle lateral motions. An experiment using a fixed-base driving simulator is conducted to measure six test subjects’ steering control behaviour in response to the lane- change manoeuvres generated by an automated steering control system. The two proposed driver models are fitted to the measured driver steering angle data to investigate their capabilities for representing individual driver’s steering control behaviour. Key model parameters are identified following a system identification procedure. It is found that the two driver models have equivalent capability for capturing the trend exhibited in all the six test subjects’ steering angle histories, but less good at reproducing the severe overshoot or oscillation involved in two subjects’ measured steering angles. It is found that the inclusion of an arm neuromuscular system model can improve the performance of the proposed driver models on representing human driver steering control behaviour.

Calls continue for the decolonisation of higher education (HE). Based on internationalisation debates, a research team from Africa, Europe and Latin America reviewed published decolonisation voices. Using bibliometric analysis and a conceptual review of abstracts, the authors examined the drivers framing decolonisation in HE and identified the voices in those debates which involved the historically oppressed and those wishing to elicit change in these debates. The paper recognises the importance for decolonisation in education as the tensions explored by the authors often intersect through HE into other domains of the political, social, economic and culturally important areas for replication and change in society.