bluuebunny/crossref_metadata_2025 huggingface dataset:
Targeted inhibition of β-catenin alleviates airway inflammation and remodeling in asthma via modulating the profibrotic and anti-inflammatory actions of transforming growth factor-β1
Authors: Huo Rujie , Tian Xinli , Chang Qin , Liu Dai , Wang Chen , Bai Jingcui , Wang Runjuan , Zheng Guoping , Tian Xinrui
Published: June 2020

Background and objective TGF-β1 is a key cytokine involved in airway inflammation and airway remodeling in asthma, owing to its anti-inflammatory and profibrotic effects. In our previous study, we found that the knockdown of cytosolic β-catenin mitigated the profibrogenic effect of TGF-β1 without affecting its anti-inflammatory effect. However, the exact role of targeting β-catenin in asthma is not yet fully demonstrated. In the present study, we investigated the effect and mechanism of targeting β-catenin in OVA-challenged asthmatic rats with airway inflammation and remodeling features. Methods We integrated experimental asthma model and asthma related cell model to explore the effect of targeting β-catenin on airway inflammation and remodeling of asthma. Results Blocking β-catenin with ICG001, a small molecule inhibitor of β-catenin/TCF via binding to CBP, attenuated airway inflammation by increasing the level of the anti-inflammatory cytokines IL-10, IL-35, and reducing the level of proinflammation cytokine IL-17. Suppressing β-catenin with ICG001 has an inhibitory effect on airway remodeling via reducing the level of TGF-β1 and the expression of MMP-7 and Snail, upregulating expression of E-cadherin, downregulating expressions of α-SMA and Fn. Inhibiting β-catenin with ICG001 suppressed TGF-β1-induced proliferation and activation of lung fibroblast (CCC-REPF-1) cells, and blocked TGF-β1-induced, blocked TGF-β1 induced EMT of alveolar type II epithelial (RLE-6TN) cells. Conclusions Blockade of β-catenin/TCF not only prevents TGF-β1 induced EMT and profibrogenic effects involved in pathological remodeling of airway, but also alleviates airway inflammation in asthma by balancing proinflammatory and anti-inflammatory cytokine.
Clinical Outcomes After Coronary Artery Bypass Grafting in Patients with Dialysis-Dependent End-Stage Renal Disease and an Analysis of the Related Influencing Factors
Authors: Li Xihui , Zhang Siyu , Xiao Feng
Published: June 2020

Backgroud Perioperative and short/mid-term survival rates of dialysis-dependent patients with end-stage renal disease (ESRD), who undergo coronary artery bypass grafting (CABG), and the factors influencing mortality are not well evaluated In China. Method We retrospectively analyzed the perioperative and postoperative 1-, 3-, and 5-year survival rates of 53 dialysis-dependent ESRD patients who underwent CABG, and compared the factors related to perioperative mortality and all-cause mortality during the postoperative follow-up. Survival rates were expressed as Kaplan–Meier survival curves, and factors influencing the follow-up survival rates were analyzed using the log rank (Mantel–Cox) test. Result There were eight perioperative deaths, resulting in 15.1% mortality. Intraoperative intra-aortic balloon pump use (P=0.01), advanced age (P=0.0027), and high EuroSCORE II score (P=0.047) were associated with increased perioperative mortality. Forty-five discharged patients were followed from 2 months to 10 years (median, 4.2 years) postoperatively. There were 19 all-cause deaths, including 10 cardiac deaths (10/19, 52.6%). Comparisons between groups indicated that the presence of peripheral artery disease (PAD) increased mortality during follow-up (P=0.025); 1-, 3-, and 5-year survival rates were 93.3%, 79.5%, and 66.8%, respectively. The results of the long-rank analysis indicated that the presence of PAD was a risk factor for postoperative survival (log rank χ 2 =4.543; P=0.033). Conclusion Dialysis-dependent patients with ESRD had high perioperative mortality and unsatisfactory short- and medium-term survival after CABG. PAD was a risk factor affecting patients’ postoperative survival. Multidisciplinary teamwork is needed to enhance postoperative management and reduce complications, to improve postoperative survival in these patients.
Choline and Bile Acids Mixture Improved Growth Performance and Intestinal Immunity via Altering Gut Microbiota and Bacterial Metabolites in the Colon of Weaned Piglets.
Authors: Qiu Yueqin , Li Kebiao , Liu Shilong , Wang Li , Gao Kaiguo , Yang Xuefen , Jiang Zongyong
Published: June 2020

Background: Choline or bile acids has many beneficial roles in physiological function. However, little was known about growth performance, intestinal mucosal function and microbiota-host interactions of weaned piglets in response to choline or bile acids supplementation. This study aimed to investigate the effect of choline and bile acids mixtures (ChB) supplementation on growth performance, intestinal mucosal barrier function, gut microbiota and bacterial metabolites of weaned piglets. One hundred and twenty-eight crossbred (Duroc × Landrace × Large White) weaned piglets (initial body weight: approximately 8 kg; 21 d of age) were randomly allocated to four different dietary treatments(a control diet (Control) and the other three groups were control diet supplemented with 800 mg/kg choline chloride (choline), 500 mg/kg bile acids (bile acids) or 800 mg/kg choline chloride plus 500 mg/kg bile acids (ChB), respectively) and for 28-d feeding trail. Results: ChB significantly increased average daily gain (ADG) and reduced feed/gain (F/G) ratio, associated with elevation of lipase activity and total bile acids level in ileal digesta compared with control diet. Additionally, ChB altered colonic microbiota by increasing the relative abundance of Lactobacillus and Faecalibacterium , and decreasing the relative abundances of unidentified-Clostridiales , Parabacteroides and Unidentified-Ruminococcaceae , when compared with control diet. Meanwhile, ChB increased the butyrate level and decreased the production of bile acid profiles in the colonic digesta. Besides, feeding ChB improved gut immunity, as reflected by increasing the abundance of IL-10 , FXR and mucin2 transcript, while downregulated expression of TLR4 , MyD88 , NF-κBp65 and TNF-α genes in the intestinal mucosa. Quantitative proteomics of jejunal mucosa further showed that ChB regulated the proteins that were related to inflammatory response. Furthermore, the changes in the ADG and genes expression were associated with alteration of gut microbiota composition and their metabolites. Conclusions: Collectively, our findings demonstrated that choline and bile acids mixture may improve the growth performance and intestinal immune response of weaned piglets through alteration of gut microbiota composition and bacterial metabolites, which promoted gut health.
Primary epithelioid angiosarcoma originating from the mandibular gingiva: a case report of an extremely rare oral lesion
Authors: Komatsu Yuko , Miyamoto Ikuya , Ohashi Yu , Katagiri Katsunori , Saito Daisuke , Obara Mizuki , Takeda Yasunori , Shiga Kiyoto , Yamada Hiroyuki
Published: June 2020

BackgroundAngiosarcoma occurs very rarely in the oral cavity, and the epithelioid type is even rarer. Here we report a rare case involving an elderly man with a primary epithelioid angiosarcoma that originated from the mandibular gingiva and resembled a dentigerous cyst on radiographs.Case presentationA 66-year-old Japanese man visited our hospital with a chief complaint of gingival swelling in right mandibular third molar region. A panoramic radiograph showed bone resorption around the crown of right mandibular third molar, which was impacted. Incisional biopsy confirmed a diagnosis of epithelioid angiosarcoma. The lesion exhibited aggressive proliferation after biopsy resulting in uncontrolled bleeding and difficulty in closing the mouth. Mandibular segmental resection including the tumor was performed without reconstruction. Because of the aggressive preoperative course of the tumor, the patient received adjuvant chemotherapy. There were no signs of recurrence during a 1-year follow-up period.ConclusionsA review of the literature yielded only three reported cases of epithelioid angiosarcoma in the jaw region, with the lesions occurring in the maxilla in all three cases. To our knowledge, this is the first case of primary epithelioid angiosarcoma in the mandible.
Puerarin Inhibits FUNDC1-mediated Mitochondrial Autophagy and CSE-induced Apoptosis of Human Bronchial Epithelial Cells by Activating the PI3K/AKT/MTOR Signaling Pathway
Authors: Wang Li , Jiang Weizhou , Wang Jing , Xie Yuanyuan , Wang Weisi
Published: June 2020

Background: Growing evidence suggests that the pathogenesis of chronic obstructive pulmonary disease (COPD) is related to mitochondrial autophagy mediated by FUN14 domain protein 1 (FUNDC1). Recent studies have shown that puerarin has protective effects against excessive oxidative damage in cells. We hypothesized that puerarin might be involved in the progression of COPD induced by cigarette smoke extract (CSE) by regulating FUNDC1-mediated mitochondrial autophagy.Material/Methods: Different concentrations of puerarin were used to intervene in CSE-treated human bronchial epithelial cells (HBECs). MTT assay and flow cytometry were used to detect cell activity and apoptosis. The mitochondrial membrane potential (MMP) level, reactive oxygen species (ROS) content and ATP content were detected by flow cytometry or kits; Western Blotting was used to detect mitochondrial autophagy-related proteins expression such as DRP1, FUNDC1, PINK1, Parkin. Next, protein phosphatase inhibitor (PH0321) was used to inhibit the phosphorylation of FUNDC1, the changes of MMP, ROS, ATP and mitochondrial autophagy related proteins were detected. Furthermore, mitochondrial autophagy inhibitors (Mdivi) were used to block autophagy, and then the changes of mitochondrial autophagy, cell activity and apoptosis were detected, respectively. Finally, the changes of PI3K/AKT/mTOR signaling pathway-related proteins were detected by Western Blotting.Results: Puerarin reversed cell activity decrease and apoptosis increase of CSE-induced HBECs, and down-regulated apoptosis-related proteins expression. Puerarin up-regulated MMP level and ATP content in CSE-induced HBECs, and down-regulated ROS content and mitochondrial autophagy-related proteins expression. PH0321 promotes mitochondrial autophagy by promoting the dephosphorylation of FUNDC1, puerarin inhibits the dephosphorylation of FUNDC1, up-regulated the MMP level and ATP content of CSE-induced HBECs, reduces ROS content and mitochondrial autophagy-related proteins expression. Compared with Mdivi group, the protein expression changes of PINK1 and Parkin in puerarin-treated group were not significantly different, and the cell activity decrease and apoptosis increase of CSE-induced HBECs were also significantly reversed by puerarin, which was not significantly different from Mdivi group. Puerarin significantly upregulated the protein expression of p-PI3K, p-AKT and p-mTOR, suggesting that puerarin may participate in the progression of COPD by activating the PI3K/AKT/mTOR signaling pathway.Conclusions: Puerarin inhibits FUNDC1-mediated mitochondrial autophagy and CSE-induced apoptosis of HBECs by activating the PI3K/AKT/mTOR signaling pathway.
Serum Amyloid a in Stable COPD Patients is Associated With the Frequent Exacerbator Phenotype
Authors: Zhao Dongxing , Abbasi Asghar , Rossiter Harry B , Su Xiaofen , Liu Heng , Pi Yuhong , Sang Li , Zhong Weiyong , Yang Qifeng , Guo Xiongtian , Zhou Yanyan , Li Tianyang , Casaburi Richard , Zhang Nuofu
Published: June 2020

Background: We sought to determine whether circulating inflammatory biomarkers were associated with the frequent exacerbator phenotypein stable COPD patients i.e. those with two or more exacerbations in the previous year.Methods:88 stable, severe, COPD patients (4 females)were assessed for exacerbation frequency, pulmonary function, fraction of expired nitric oxide (FENO);inflammatory variables were measured in venous blood. Logistic regression assessed associations between the frequent exacerbator phenotype and systemic inflammation.Results:Compared with infrequent exacerbators, frequent exacerbators (n=10; 11.4%)had greater serum concentration(median (25th-75th quartile)) of serum amyloid A (SAA; 134(84-178) vs. 71(38-116) ng/ml; P=0.024), surfactant protein D (SP-D;15.6(9.0-19.3)vs. 8.5(3.6-14.9) ng/ml; P=0.049) and interleukin-4 (IL-4; 0.12(0.08-1.44)vs. 0.03(0.01-0.10) pg/ml;P=0.001). SAA,SP-D and IL-4were not significantly correlated with FEV1 %predicted or FVC %predicted. After adjusting for sex, age, BMI, FEV1/FVC and smoking pack-years, only SAA remained independently associated with the frequent exacerbator phenotype (OR 1.49[1.09-2.04]; P=0.012).The odds of being a frequent exacerbator was 18-times greater in the highest SAA quartile (³124.1ng/ml) than the lowest SAA quartile (£44.1ng/ml) (OR 18.34[1.30-258.81]; P=0.031), and there was a significant positive trend of increasing OR with increasing SAA quartile (P=0.008). For SAA, the area under the receiver operating characteristic curve was 0.721 for identification of frequent exacerbators with an optimal SAA cut-offof 131.7 ng/ml.Conclusion: In stable COPD patients, SAA was independently associated with the frequent exacerbator phenotype, suggesting that SAA maybe a usefulserum biomarker to inform progression or management in COPD.
Estrogen-Related Receptor-α Promotes Pancreatic Cancer Progression by Enhancing the Transcription of PAI1 and Activating the MEK/ERK Signaling Pathway
Authors: Liu Shi-lei , Wu Xiang-song , Li Feng-nan , Yao Wen-yan , Wu Zi-you , Dong Ping , Wang Xue-feng , Gong Wei
Published: June 2020

Background: Estrogen-related receptor alpha (ERRα), an orphan nuclear receptor, was reported to be highly associated with the progression and tumorigenesis of several human malignancies. However, the biological role and underlying molecular mechanisms of ERRα in pancreatic cancer (PC) remain unknown.Methods: The expression of ERRα in PC tissues was determined by qRT-PCR and immunohistochemistry. A series of in vitro and in vivo assays were performed to investigate the function of ERRα and Plasminogen activator inhibitor 1 (PAI1) in tumorigenesis in PC cells. The relationship between ERRα and PAI1 was identified by RNA sequencing, Chromatin immunoprecipitation and dual-luciferase reporter assays. The effects of ERRα on the MEK/ERK signaling pathway were determined by western blotting and rescue assays using ERK inhibitor GDC-0994.Results: ERRα was significantly overexpressed in PC tissues and cell lines. Its high expression was correlated with tumor size, distant metastasis, TNM stage, tumor differentiation and poor prognosis of PC. Subsequent functional assays showed that ERRα promoted PC cell proliferation, tumor growth, as well as migration and invasion via activating the epithelial-mesenchymal transition. In addition, knockdown of ERRα induced apoptosis and G0/G1 cell cycle arrest in PC cells. PAI1 was identified by RNA sequencing, knockdown of which could suppress the cell proliferation, migration and invasion that promoted by ERRα overexpression. Further mechanistic investigation using chromatin immunoprecipitation and dual-luciferase reporter assays revealed that ERRα could bind to the PAI1 promoter region and transcriptionally enhance PAI1 expression. Moreover, our data indicated that ERRα played its oncogenic role in PC via activating the MEK/ERK pathway.Conclusions: Our study demonstrates that ERRα promotes PC progression by enhancing the transcription of PAI1 and activation of the MEK/ERK pathway, pointing to ERRα as a novel diagnostic and therapeutic target for PC.
A New Scoring System Combining A Four-Section Honeycomb Lung Percentage on HRCT and Other Comprehensive Multiparameter for Evaluating Pulmonary Fibrosis Severity
Authors: Yin Chengsheng , Zhang Yuan , Su Yiliang , Zhang Feng , Shi Jingyun , Chen Yanan , Weng Dong , Chen Tao , Zhao Mengmeng , Zhou Ying , Jiang Xing , Zhang Aihong , Li Huiping
Published: June 2020

Background: How to accurately assess IPF severity and predict prognosis remains a problem. This study aimed to develop a new method, which can be easily used to assess pulmonary fibrosis severity.Method:1. Development of a HRCT combined pulmonary function & physiological parameter (CTPF) assessment method: The method included two parts. 1) CT-based fibrosis staging: Four representative lung CT sections were selected and evenly divided into 100 small areas. The percentage of honeycomb lesion area in the four sections was determined fibrosis stage,2) PF-based severity grade: FVC%pred,DLco%pred,SpO2% age and gender were used to assess PF severity grade. 2. Validation of the new method: The method was used to assess 192 patients with IPF. Two radiologists used the CT-based fibrosis staging method to determine the fibrosis stage. Pulmonologist determined the PF severity grade. 3. Statistical analyses: By Intra-group correlation coefficient and Spearman correlation coefficient to estimate the consistency between the CT scores from the two radiologists and the correlation between CT scores and lung function parameters. Using the competitive risk Fine–Gray model to analyze the relationship between CT-based stage/PF-based grade and prognosis. CT-based stage, PF-based grade, and GAP stage were used as predictor models to predicted the death risk. Results: 1. The intra-group correlation coefficient of the CT scores of the two radiologists was 0.95, P<0.05. 2. The CT scores negatively correlated with pulmonary function. 3. The CTPF comprehensive model, showed higher predictive accuracy.Conclusion: Combined CT-based staging and PF-based grading methods CTPF can be adopted easily in clinical practice, and can assess IPF severity and predict death risk more accurately.
Polyhexamethylene Guanidine-induced Lung Injuries and Tumorigenesis in a Rat Model: Radiologic Evaluation With Pathologic Correlation and RNA Sequencing
Authors: Kim Cherry , Jeong Sang Hoon , Kim Jaeyoung , Lee Ki Yeol , Cha Jaehyung , Lee Chang Hyun , Park Eun-Kee , Lee Ju-Han
Published: June 2020

Background: Polyhexamethylene guanidine phosphate (PHMG) is was used as humidifier disinfectants. We aimed to evaluate PHMG-induced lung injuries and their chronological changesin a rat model using chest CT with pathologic correlation, to determine whether PHMG exposure causes lung tumors, and to explore genetic alterations according to PHMG exposure under the guidance of CT.Methods: A PHMG solution was intratracheally administrated to 40 male rats. Chest CT was carried out in all rats and both lungs were collected for histopathologic evaluation. At 4 weeks after instillation, one lobe of the right lung from 3 rats was subjected to RNA sequencing.Results: At least one abnormal CT finding was found in all rats at all weeks. The major CT findings were inflammation, fibrosis, and tumors in the pathologic analysis, where significant changes were observed over time.The lung lesions remained persistent after 8 weeks of PHMG exposure. In the pathologic analysis, the extent/severity of inflammation did not show statistically significant changes over time, whereas the extent/severity of fibrosis increased continuously up to 6 weeks after PHMG exposure and then decreased significantly at 8 weeks. Bronchiolar-alveolar adenomas which have malignant potential were found in 50% of rats at 6 and 8 weeks after PHMG exposure. Also, several genes associated with lung cancer, acute lung injury, and pulmonary fibrosis were detected.Conclusions: PHMG-induced lung injury and its changes according to the number of weeks after exposure were demonstrated using chest CT and pathologic evaluation. In addition, we showed that PHMG exposure caused lung tumors and genetic alterations according toPHMG exposure under the guidance of CT.
Feasibility of intraoperative radiotherapy with X-rays for the treatment of superior sulcus tumours
Authors: PAN YI , Yang Xuening , Chen Zhiyong , Liang Yu , Hou Qingyi , Liao Riqiang , Dong Song , Xie Songxi , Zhong Wenzhao , Wu Yi-Long
Published: June 2020

Background

Preoperative concurrent chemoradiotherapy (CCRT) followed by surgery has become the standard treatment for potentially resectable superior sulcus (SS) tumours. To date, intraoperative radiotherapy (IORT) for SS tumour treatment is primarily performed via brachytherapy; it achieves high local control, but has no influence on overall survival. Therefore, a novel therapy is required to increase the local control of SS tumours. The purpose of this study was to evaluate the feasibility and safety of IORT with low-energy X-rays for treating SS tumours.

Methods

Patients diagnosed with stage IIB-IIIA SS tumours with chest wall invasion and scheduled to undergo surgery were eligible for this prospective pilot study. Every patient was discussed at a lung cancer multidisciplinary team meeting. Patients with potentially resectable tumour were scheduled for neoadjuvant chemoradiotherapy followed by surgery, while those with resectable tumour were scheduled to receive surgery alone. Neoadjuvant chemotherapy consisted of two cycles of platinum-based doublet chemotherapy. Concurrent radiotherapy of 50 Gy in 25 fractions over 5 weeks was performed via intensity-modulated radiation therapy. IORT was administered to the tumour bed with close margin. The primary endpoint was acute toxicity and secondary endpoints were late spinal cord and brachial plexus toxicity.

Results

Between August 22, 2014 and November 30, 2017, we enrolled nine patients (seven males and two females). Anaemia was the most common acute complication, with grade 3 anaemia occurring in three patients who received preoperative CCRT. Other side effects included pneumonia (1 patient), prolonged air leakage (1), and grade 1 brachial plexus injury (1). The average follow-up period was 29.4 (range; 13.3-50.4) months. All patients are alive. Distant metastasis was observed in two patients, one with contralateral lung metastasis and another with pericardial metastasis.

Conclusions

IORT with low-energy X-rays is a technically feasible and relatively safe treatment modality for patients with superior pulmonary sulcus tumours.
Pegylated recombinant human arginase 1 induces autophagy and apoptosis via the ROS-activated AKT/mTOR pathway in bladder cancer cells
Authors: Zhao Zhuyun , Zhang Peng , Li Wei , Wang Dengchuan , Ke Changneng , Liu Yueming , Ho James Chung-Man , Cheng Paul Ning-Man , Xu Shi
Published: June 2020

Background
Bladder cancer is one of the dominant cancers worldwide, especially for male. Currently, the therapeutical regimen of bladder cancer is based on surgery, radiation therapy, chemotherapy and immunotherapy, but the clinical outcome is still needed to improve. Recombinant human arginase (rhArg, BCT-100) is a novel agent to show great anticancer effect on arginine auxotrophic tumor. However, the effect of rhArg on bladder cancer still remains unclear.
Methods
A panel of six bladder cancer cell lines (BIU-87, EJ-1, J82, SCaBER, T24 and 5637) was employed to assess the anticancer effect of BCT-100 in vitro by MTT assay. T24 nude mice xenograft models were established to evaluate the anticancer effect of BCT-100 in vivo. Protein level (argininosuccinate synthetase 1 (ASS1), ornithine transcarbamylase, cleaved-PARP, PEG, Survivin, p62, Beclin-1, LC3B, p-AKT, p-mTOR) was detected by Western blot. Intracellular, serum and intratumoral arginine concentrations were examined by ELISA. Apoptotic rate, H2O2 and mitochondrial membrane depolarization were tested by flow cytometer. Immunoflorescence on ki67 and TUNEL assay were applied to identify cellular and tumoral apoptotic events.
Results
BCT-100 displayed anticancer effects on bladder cancer cells in vitro and in vivo. The expression of ASS1 varies in different bladder cancer cell lines, and ornithine transcarbamylase is almost deficient except weakly expressed in SCaBER cell line. Knockdown ASS1 in BIU-87 cells could enhance the cytotoxicity induced by BCT-100. Intracellular arginine level was sharply decreased followed by apoptotic events. Futhermore, BCT-100 induced H2O2 production and mitochondrial membrane depolarization, leading to cytochrome c and smac released from mitochondria to cytosol. The expression of LC3B and Becllin-1 was up-regulated, while p62 was down-regulated in a time dependent manner. Autophagic flux was also observed upon BCT-100 treatment. Besides, the phosphorylation of AKT/mTOR pathway was suppressed in a time dependent fashion in BCT-100-treated T24 cells. N-Acetyl-L-cystein reduced the apoptosis and autophagy induced by BCT-100, while CQ, MK-2206 and rapamycin potentiated the apoptosis triggered by BCT-100.
Conclusions
The present study demonstrated that BCT-100 induced autophagy and apoptosis via ROS mediated AKT/mTOR signaling pathway in bladder cancer cells.
Assessing training needs in infectious disease management at major ports, airports and ground-crossings in Europe
Authors: de Rooij Doret , Belfroid Evelien , Hadjichristodoulou Christos , Mouchtouri Varvara A. , Raab Jörg , Timen Aura
Published: June 2020

Background: The implementation of core capacities as stated in the International Health Regulations (IHR) is far from complete, and, as the COVID-19 pandemic shows, the spreading of infectious diseases through points of entry (POEs) is a serious problem. To guide training and exercises, we performed a training needs assessment on infectious disease management among professionals at European POE. Methods: We disseminated a digital questionnaire to representatives of designated airports, ports, and ground-crossings in Europe. Topics were derived from the IHR core capacities for POEs. Based on the importance (4-point Likert scale) and training needs (4-point Likert scale), we identified the topics with the highest priority for training. These results were put in further perspective using prior experience (training <3 year, exercise <5 years, events <5 years). Also, preferences for training methodologies were assessed. Results: Fifty questionnaires were included in the analyses, representing 50 POEs from 19 European countries. Importance is high for 26/30 topics, although scores widely vary among respondents. Topics with a high training need (16/30) are amongst others the handling of ill travelers; using and composing the public health emergency contingency plan, and public health measures. Respondents from ports and airports attribute equal importance to most topics, but respondents from ports showed higher training needs on 75% of the topics. POEs are unevenly and generally little experienced. The most preferred training methods were presentations. Simulation is the preferred methodology for training the handling of ill or exposed travelers. Conclusions: The European workforce at designated ports, airports and ground-crossings has a different level of experience and perceives varying importance of the topics assessed in our study. We identified the topics on which training is required. We call for European collaboration between POEs to agree upon the importance of infectious disease management, and to jointly build a trained and prepared workforce that is ready to face the next crisis.
Psychological consequences of COVID-19 pandemic in Italian MS patients: signs of resilience?
Authors: Capuano Rocco , Altieri Manuela , Bisecco Alvino , d'Ambrosio Alessandro , Docimo Renato , Buonanno Daniela , Matrone Federica , Giuliano Federica , Tedeschi Gioacchino , Santangelo Gabriella , Gallo Antonio
Published: June 2020

Background: Anxiety, depression and reduction of quality of life (QoL) are common in people with multiple sclerosis (pwMS). Fear of getting sick from COVID-19, government’s lockdown and the imposed social distancing might have an impact on psychological distress and QoL. Objectives: The aim of our study was to investigate anxiety, depression and QoL changes in pwMS during SARS-CoV-2 outbreak and lockdown in Italy.Methods: 67 pwMS with a previous (less than 6 months) neuropsychological evaluation before SARS-CoV-2 outbreak (T0) were re-evaluated at the time of the outbreak and lockdown in Italy (T1). They underwent a clinical and neurological evaluation (at T0) and completed the State-Trait Anxiety Inventory (STAI-Y1), the Beck Depression Inventory second edition (BDI-II), and Multiple Sclerosis Quality of Life-54 (MsQoL-54) at T0 and T1. Bonferroni correction for multiple comparisons was applied.Results: BDI-II and STAI-Y1 scores did not change between T0 and T1, whereas the satisfaction on sexual function subscale of MsQoL-54 was significantly higher at T1 (p<0.001).Conclusions: This is the first study that evaluated mood and QoL levels before and during the lockdown due to COVID-19 pandemic in pwMS. No worsening of anxiety and depression levels was found. Contrariwise, some improvements were noted on QoL, the most reliable regarding the sexual satisfaction.
Search for therapeutics against COVID 19 targeting SARS-CoV-2 papain-like protease: an in silico study
Authors: Laskar Monjur Ahmed , Choudhury Manabendra Dutta
Published: June 2020

Background: The global pandemic of novel coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is an enveloped, positive-sense, single-stranded RNA betacoronavirus of the family Coronaviridae. Papain-like protease (PLpro) of SARS CoV-2 is an important target of COVID-19 because it is a multifunctional cysteine protease essential for coronaviral replication. Large numbers of phytochemicals with varied chemical structures isolated from medicinal plants have been shown to possess antiviral activity. Some of these phytochemicals have been chosen on the basis of literature survey for this study. Reported inhibitors of the papain-like protease are taken as control and for QSAR study.Methods: Three dimensional structure of target was downloaded from Protein Data Bank and docked with phytochemicals & inhibitors by using software FlexX. Inhibitors of the papain-like protease were taken from binding database and QSAR analysis was performed by using EasyQSAR software.Results: Six phytochemicals: Baicalin, Rutin, Biopterin, Licoleafol, Luteolin and Quercetin shows stable bonding pattern with the target in compare to known inhibitors as it shows least score in docking, forms maximum number of hydrogen bonds with the active residues of the receptor. The predicted IC50 values of the phytochemicals are also better than the known inhibitors.Conclusion: Based on present observation of docking score of both phytochemicals and known inhibitors, IC50 value of known inhibitors and predicted IC50 of phytochemicals, we suggests above mentioned six phytochemicals may be the Papain-like protease (PLpro) targeted potent drug leads against Covid-19.
Outpatient management or hospitalization of patients with proven or suspected SARS-CoV-2 infection: The HOME-CoV rule.
Authors: D. Douillet , R. Mahieu , V. Boiveau , Y.-M. Vandamme , A. Armand , F. Morin , D. Savary , V. Dubée , C. Annweiler , P.-M. Roy
Published: June 2020

In the context of the COVID-19 pandemic and overloaded hospitals, a central issue is the need to define reliable and consensual criteria for hospitalization or outpatient management in mild cases of COVID-19. Our aim was to define an easy-to-use clinical rule aiming to help emergency physicians in hospitalization or outpatient management decision-making for patients with suspected or confirmed SARS-CoV-2 infection (the HOME-CoV Rule). The Delphi method was used to reach a consensus of a large panel of 51 experts: emergency physicians, geriatricians, infectious disease specialists, and ethical consultants. A preliminary list of eligible criteria was compiled based on a literature review. Four rounds of anonymized expert consultations were performed. The experts were asked to score each item as relevant, possibly relevant and non-relevant, as major or minor, and to choose the cut-off. They were also able make suggestions and remarks. Eight criteria constituting the HOME-CoV were selected: six correspond to the severity of clinical signs, one to the clinical course (clinically significant worsening within the last 24 hours), and the last corresponds to the association of a severe comorbidity and an inadequate living context. Hospitalization is deemed necessary if a patient meets one or more of the criteria. In the end, 94.4% of the experts agreed with the defined rule. Thanks to the Delphi method, an absolute consensus was obtained of a large panel of experts on the HOME-CoV rule, a decision-making support mechanism for clinicians to target patients with suspected or confirmed COVID-19 requiring hospitalization.Trial registration: NCT04338841
The braincase of Bissektipelta archibaldi — new insights into endocranial osteology, vasculature, and paleoneurobiology of ankylosaurian dinosaurs
Authors: Kuzmin Ivan , Petrov Ivan , Averianov Alexander , Boitsova Elizaveta , Skutschas Pavel , Sues Hans-Dieter
Published: June 2020

We describe in detail three braincases of the ankylosaur Bissektipelta archibaldi from the Late Cretaceous (Turonian) of Uzbekistan with the aid of computed tomography, segmentation, and 3D modeling. Bissektipelta archibaldi is confirmed as a valid taxon and attributed to Ankylosaurinae based on the results of a phylogenetic analysis. The topographic relationships between the elements forming the braincase are determined using a newly referred specimen with preserved sutures, which is an exceedingly rare condition for ankylosaurs. The mesethmoid appears to be a separate ossification in the newly referred specimen ZIN PH 281/16. We revise and discuss features of the neurocranial osteology in Ankylosauria and propose new diagnostic characters for a number of its subclades. We present a 3D model of the braincase vasculature of Bissektipelta and comment on vascular patterns of armored dinosaurs. A complex vascular network piercing the skull roof and the wall of the braincase is reported for ankylosaurs for the first time. We imply the presence of a lepidosaur-like dorsal head vein and the venous parietal sinus in the adductor cavity of Bissektipelta. We suggest that the presence of the dorsal head vein in dinosaurs is a plesiomorphic diapsid trait, and extant archosaur groups independently lost the vessel. A study of two complete endocranial casts of Bissektipelta allowed us to compare endocranial anatomy within Ankylosauria and infer an extremely developed sense of smell, a keen sense of hearing at lower frequencies (100–3000 Hz), and the presence of physiological mechanisms for precise temperature control of neurosensory tissues at least in derived ankylosaurids.
GAMESS As a Free Quantum-Mechanical Platform for Drug Research
Authors: Alexeev Yuri , Mazanetz Michael P. , Ichihara Osamu , Fedorov Dmitri G.
Published: June 2020

Driven by a steady improvement of computational hardware and significant progress in ab initio method development, quantum-mechanical approaches can now be applied to large biochemical systems and drug design. We review the methods implemented in GAMESS, which are suitable to calculate large biochemical systems. An emphasis is put on the fragment molecular orbital method (FMO) and quantum mechanics interfaced with molecular mechanics (QM/MM). The use of FMO in the protein-ligand binding, structure-activity relationship (SAR) studies, fragment- and structure-based drug design (FBDD/SBDD) is discussed in detail.
Feasibility of Relative Strain Index (RSI) for the Assessment of Heat Stress in Outdoor Environments: Case Study in Three Different Climates of Iran
Authors: Asghari Mehdi , Ghalhari Gholamabbas Fallah , Abbasinia Marzieh , Shakeri Fahimeh , Tajik Reza , Ghannadzadeh Mohammad Javad
Published: June 2020

Objectives:

Different indices are used to evaluate heat stress in outdoor environments. This study was aimed at examining the applicability of the Relative Strain Index (RSI) to the assessment of heat stress in several climates of Iran.

Methods:

Based on the Köppen classification, three different climates were studied. Arak, Bandar Abbas, and Sari were selected as representative of semi-arid and cold climates, hot and dry, and Mediterranean, respectively. The data recorded by the meteorological organization, including air temperature, relative humidity and air velocity were surveyed during 15-year period in three different climates. The RSI index was calculated by the formula. Also, the Wet Bulb Globe Temperature (WBGT) index was computed using a model presented by the Australian Bureau of Meteorology (ABM). Data were analyzed using SPSS v.22, descriptive statistics, Pearson correlation coefficient, and linear regression.

Results:

The mean RSI index in summer of the 15 years in Arak was 0.033 ± 0.33, in Bandar Abbas 0.54 ± 0.6 and for Sari was 0.17 ± 0.05. A high correlation was found between environmental variables and RSI index in three different climates. As well, there was a positive and significant correlation between both RSI and WBGT indices in three different climates (R2>0.96).

Conclusion:

The RSI index is a simple and empirical index and can be used for the evaluation of heat stress along with other indices. The index estimates the situation more than expected to be stressful in warm and dry conditions. So, it is not a useful index for hot and dry climates such as Bandar Abbas.
Akuntabilitas dan transparansi manajemen keuangan dalam mensejahterakan guru dan anak didik di TK Alfadlillah Maguwoharjo Yogyakarta
Authors: Ulfa Maria
Published: June 2020

Alasan penelitian ini berawal dari ketertarikan peneliti terhadap perubahan sekolah setelah menggunakan prinsip-prinsip manajemen pembiayaan, salah satunya yaitu akuntabilitas dan transparansi. Sebelum menerapkan dua prinsip ini, antara guru dan kepala sekolah tidak saling terbuka terkait manajemen pembiayaan, sehingga terdapat sejumlah uang yang disalahgunakan oleh kepala sekolah. Tetapi setelah pergantian kepala sekolah, kemudian dua prinsip ini diterapkan. Hal ini mendatangkan banyak perubahan dan manfaat tidak hanya kepada guru-guru sebagai pengajar, akan tetapi orang tua dan anak didik yang berada di dalamnya lebih interaktif dan komunikatif. Dengan adanya perubahan ini guru merasa lebih sejahtera. Tidak hanya guru, permainan anak-anak juga semakin bertambah banyak. Peneliti mengamati setiap fenomena yang terjadi di lapanan hingga memperoleh sebuah makna. Peneliti menggunakan metode penelitian kualitatif deskriptif. Subjek penelitian di TK Alfadlillah Maguwoharjo Yogyakarta. Peneliti mengumpulkan data melalui tiga cara yaitu, observasi, wawancara dan dokumentasi. Adapun hasil penelitian ini ialah: dengan akuntabel dan transparansinya manajemen keuangan, membuat antar guru saling terbuka dan memahami kebutuhan sekolah, guru semakin memiliki ikatan keluarga, merasa lebih sejahtera, melalui uang tersebut dapat mendesain kelas, dan menambah permainan outdoor serta tidak ada kecemburuan sosial.
Implementasi permainan tradisional dalam pembelajaran anak usia dini sebagai pembentuk karakter bangsa
Authors: Adi Banu Setyo , Sudaryanti Sudaryanti , Muthmainah Muthmainah
Published: June 2020

Permainan tradisional memiliki manfaat yang beragam untuk pengembangan anak usia dini, termasuk membentuk karakter anak usia dini. Program pelatihan ini bertujuan untuk meningkatkan pemahaman guru tentang cara memodifikasi permainan tradisional, kemudian menerapkannya dalam pembelajaran, serta mendiseminasikan kepada kolega guru lainnya. Metode kegiatan ini dilaksanakan melalui tiga tahap yaitu persiapan, pelaksanaan, dan evaluasi. Adapun hasil dari kegiatan yaitu berupa empat permainan tradisional modifikasi untuk anak usia Kelompok Bermain (2-4 tahun) meliputi Lingkaran binatang (mengembangkan dari permainan tradisional Jamuran), Tanaman keliling (mengembangkan dari permainan tradisional Cublak-cublak suweng), Sayuran (mengembangkan dari permainan tradisional Jamuran), dan Lompat rintangan (mengembangkan dari permainan tradisional lompat tali), serta tiga permainan tradisional modifikasi untuk anak usia 5-6 tahun meliputi: Menara menari (mengembangkan dari permainan tradisional Boi-boi an), Bermain sebut nama (mengembangkan dari permainan tradisional Cublak-cublak suweng), dan Jamuran jeneng kewan (mengembangkan dari permainan tradisional Jamuran). Hasil evaluasi menunjukkan bahwa lebih dari 90% peserta pelatihan memahami pengembangan modifikasi permainan tradisional untuk mengembangkan karakter anak usia dini.
The Effectiveness of Digital Health Interventions in the Management of Musculoskeletal Conditions: Systematic Literature Review (Preprint)
Authors: Hewitt Stephanie , Sephton Ruth , Yeowell Gillian
Published: June 2020

BACKGROUND

Musculoskeletal conditions are the second greatest contributor to disability worldwide and have significant individual, societal, and economic implications. Due to the growing burden of musculoskeletal disability, an integrated and strategic response is urgently required. Digital health interventions provide high-reach, low-cost, readily accessible, and scalable interventions for large patient populations that address time and resource constraints.

OBJECTIVE

This review aimed to investigate if digital health interventions are effective in reducing pain and functional disability in patients with musculoskeletal conditions.

METHODS

A systematic review was undertaken to address the research objective. The review was conducted in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. The review protocol was registered with the International Prospective Register of Systematic Reviews before commencement of the study. The following databases were searched: Medical Literature Analysis and Retrieval System Online (MEDLINE), Excerpta Medica database (EMBASE), Cumulative Index to Nursing and Allied Health Literature, and Scopus from January 1, 2000, to November 15, 2019, using search terms and database specific−medical subject headings terms in various combinations appropriate to the research objective.

RESULTS

A total of 19 English language studies were eligible for inclusion. Of the 19 studies that assessed musculoskeletal pain, 9 reported statistically significant reductions following digital intervention. In all, 16 studies investigated functional disability; 10 studies showed a statistically significant improvement. Significant improvements were also found in a range of additional outcomes. Due to the heterogeneity of the results, a meta-analysis was not feasible.

CONCLUSIONS

This review has demonstrated that digital health interventions have some clinical benefits in the management of musculoskeletal conditions for pain and functional disability. Digital health interventions have the potential to contribute positively toward reducing the multifaceted burden of musculoskeletal conditions to the individual, economy, and society.

CLINICALTRIAL

PROSPERO CRD42018093343; https://www.crd.york.ac.uk/prospero/display_record.php?RecordID=93343
Prediction of (Non)Participation of Older People in Digital Health Research: Exergame Intervention Study (Preprint)
Authors: Poli Arianna , Kelfve Susanne , Klompstra Leonie , Strömberg Anna , Jaarsma Tiny , Motel-Klingebiel Andreas
Published: June 2020

BACKGROUND

The use of digital technologies is increasing in health care. However, studies evaluating digital health technologies can be characterized by selective nonparticipation of older people, although older people represent one of the main user groups of health care.

OBJECTIVE

We examined whether and how participation in an exergame intervention study was associated with age, gender, and heart failure (HF) symptom severity.

METHODS

A subset of data from the HF-Wii study was used. The data came from patients with HF in institutional settings in Germany, Italy, the Netherlands, and Sweden. Selective nonparticipation was examined as resulting from two processes: (non)recruitment and self-selection. Baseline information on age, gender, and New York Heart Association Functional Classification of 1632 patients with HF were the predictor variables. These patients were screened for HF-Wii study participation. Reasons for nonparticipation were evaluated.

RESULTS

Of the 1632 screened patients, 71% did not participate. The nonrecruitment rate was 21%, and based on the eligible sample, the refusal rate was 61%. Higher age was associated with lower probability of participation; it increased both the probabilities of not being recruited and declining to participate. More severe symptoms increased the likelihood of nonrecruitment. Gender had no effect. The most common reasons for nonrecruitment and self-selection were related to physical limitations and lack of time, respectively.

CONCLUSIONS

Results indicate that selective nonparticipation takes place in digital health research and that it is associated with age and symptom severity. Gender effects cannot be proven. Such systematic selection can lead to biased research results that inappropriately inform research, policy, and practice.

CLINICALTRIAL

ClinicalTrial.gov NCT01785121, https://clinicaltrials.gov/ct2/show/NCT01785121
Self-Policing COVID-19 and Civic Responsibilities in Lagos Metropolis, Nigeria: An Online Qualitative Study (Preprint)
Authors: Ilori Ayomide
Published: June 2020

UNSTRUCTURED

This study investigated self-policing COVID-19 and civic responsibilities in Lagos Metropolis, Nigeria adopting an online qualitative interview due to the current lockdown that denied field (face to face) interview. Fifty out of the feedbacks from the online interview were picked randomly to arrive at the conclusion of this study. The feedbacks suggested that there is adequate awareness of the COVID-19 pandemic among the people living in Lagos Metropolis, Nigeria and that they are following the directives of federal and state governments in an effort to reduce the community transmission of the infectious diseases. However, the ban on public gatherings and movements has made it impossible for many homes to meet their basic needs especially feeding. The government provided palliatives have also been largely insufficient to cater for the vulnerable. There could be a crisis (such as hunger) and the breakdown of law and order if the government does not increase their capacity to mitigate the hardship which the ongoing lockdown has imposed on the people.

INTERNATIONAL REGISTERED REPORT

RR2-https://doi.org/10.1101/2020.05.08.20092080
Maximizing the Potential of Patient-Reported Assessments by Using the Open-Source Concerto Platform With Computerized Adaptive Testing and Machine Learning (Preprint)
Authors: Harrison Conrad , Loe Bao Sheng , Lis Przemysław , Sidey-Gibbons Chris
Published: June 2020

UNSTRUCTURED

Patient-reported assessments are transforming many facets of health care, but there is scope to modernize their delivery. Contemporary assessment techniques like computerized adaptive testing (CAT) and machine learning can be applied to patient-reported assessments to reduce burden on both patients and health care professionals; improve test accuracy; and provide individualized, actionable feedback. The Concerto platform is a highly adaptable, secure, and easy-to-use console that can harness the power of CAT and machine learning for developing and administering advanced patient-reported assessments. This paper introduces readers to contemporary assessment techniques and the Concerto platform. It reviews advances in the field of patient-reported assessment that have been driven by the Concerto platform and explains how to create an advanced, adaptive assessment, for free, with minimal prior experience with CAT or programming.
Shouting into the Constitutional Void: Section 28 and Bill 21
Authors: Froc Kerri A
Published: June 2020

For several years now, I have been arguing that section 28 of the Canadian Charter of Rights and Freedoms1 is more than a symbolic flourish, more than just emphasis for section 15’s sex equality guarantee, and more than an interpretive provision. In fact, it has its own independent work to do. This includes blocking attempts by government to use section 33 to preserve gender inequality.