bluuebunny/crossref_metadata_2025 huggingface dataset:
A novel nomogram to predict the overall survival in esthesinoeroblastoma
Authors: Jiang Lijie , Lin Tengjiao , Zhang Yu , Gao Wenxiang , Deng Jie , Xu Zhaofeng , Luo Xin , Huang Zhaoqi , Chen Fenghong , Shi Jianbo , Lai Yinyan
Published: September 2020

Background: Increasing evidence indicates that the pathology and the modified Kadish system have some influence on the prognosis of esthesioneuroblastoma (ENB). However, an accurate system to combine pathology with a modified Kadish system has not been established. Methods: This study aimed to set up and evaluate a model to predict overall survival (OS) accurately in ENB, including clinical characteristics, treatment and pathological variables. We screened the information of patients with ENB between January 1, 1976, and December 30, 2016 from the National Cancer Institute Surveillance, Epidemiology, and End Results (SEER) program as a training cohort. The validation cohort consisted of patients with ENB at Sun Yat-sen University Cancer Center and The First Affiliated Hospital of Sun Yat-sen University in the same period, and 87 patients were identified. The Pearson’s chi-squared test was used to assess significance of clinicopathological and demographic characteristics. We used the Cox proportional hazards model to examine univariate and multivariate analyses. The model coefficients were used to calculate the Hazard ratios (HR) with 95% confidence intervals (CI). Prognostic factors with a p- value < 0.05 in multivariate analysis were included in the nomogram. The concordance index (c-index) and calibration curve were used to evaluate the predictive power of the nomogram. Results: The c-index of training cohort and validation cohort are 0.737 (95% CI, 0.709 to 0.765) and 0.791 (95% CI, 0.767 to 0.815) respectively. The calibration curves revealed a good agreement between the nomogram prediction and actual observation regarding the probability of 3-year and 5-year survival. We used a nomogram to calculate the 3-year and 5-year growth probability and stratified patients into three risk groups. Conclusions: The nomogram provided the risk group information and identified mortality risk and can serve as a reference for designing a reasonable follow-up plan.
Efficient Preparation of Nanoparticles Reinforced Nickel-based Composite Coating with Highly Preferred (220) Orientation
Authors: Ji Renjie , Jin Hui , Liu Yonghong , Dong Tiancong , Zhang Fan , Zhao Lilong , Wu Xinlei , Sun Qiang , Liu Peng , Dong Hang , Ma Chi , Li Dege , Cai Baoping
Published: September 2020

Nanoparticles reinforced metal matrix composite coatings have great application potential in mechanical parts surface strengthening due to their excellent mechanical properties. This paper reports a phenomenon that the grain orientation gradually evolves to (220) with the deposition current density increasing when preparing nanoparticles reinforced nickel-based composite coatings by jet electrodeposition (JED). During the preparation of Ni-SiC composite coatings, the deposition current density increases from 180 A/dm2 to 220 A/dm2, and TC(220) gradually increases from 41.4% to 97.7% correspondingly. With the increase of TC(220), the self-corrosion potential increases from -0.575 V to -0.477 V, the corrosion current density decreases from 9.52 μA·cm2 to 2.76 μA·cm2, the diameter of corrosion pits that after 10 days of immersion in 3.5 wt% NaCl solution decreases from 278~944 nm to 153~260 nm, and the adhesion of the coating is increased from 24.9 N to 61.6 N. Compared with conventional electrodeposition (CED), the Ni-SiC composite coating prepared by JED has the advantages of smooth surface morphology, corrosion resistance and strong adhesion, which is more obvious with the increase of TC (220).
Reversibility of hAT-MSCs phenotypic and metabolic changes after exposure to and withdrawal form HCC-conditioned medium through regulation of the ROS/MAPK/HIF-1α signalling pathway
Authors: Wang Chenyang , Hu Jie , Chen Zheng , Wang Yifan , Lu Sinan , Zhang Yuan , Li Yufeng , Xiang Yucheng , Ji Yutian , Zeng Cheng , Ding Yuan , Wang Weilin
Published: September 2020

Background: Mesenchymal stem cells (MSCs) play an important role in tumor progression; concomitantly, MSCs also undergo profound changes in the tumor microenvironment (TME). These changes can directly impact the application and efficacy of MSC-based anti-tumor therapy. However, few studies have focused on the regulation of MSC fate in TME, which will limit the progress of MSC-based anti-tumor therapy. Herein, we investigated the effects of conditioned medium from human hepatocellular carcinoma cells (HCC-CM) on the phenotype and glucose metabolism of human adipose tissue-derived MSCs (hAT-MSCs). Methods: The passage 2 (P2) to passage 3 (P3) hAT-MSCs were exposed to conditioned medium from Hep3B, Huh7 and HCCLM3 cells for 4-8 weeks in vitro. Then, immunofluorescent, CCK-8 assay, EdU assay, Transwell assay, and flow cytometry were used to assess the alterations in cell phenotype in terms of cell morphology, secretory profiles, proliferation, migration, invasion, cell cycle, and apoptosis. In addition, glucose metabolism was evaluated by related kits. Next, the treated hAT-MSCs were subjected to withdrawal from HCC-CM for 2-4 weeks, and alterations in phenotype and glucose metabolism were reevaluated. Finally, the molecular mechanism was clarified by Western blotting. Results: The results revealed that after exposure to HCC-CM, hAT-MSCs developed a stellate-shaped morphology. In association with cytoskeleton remodelling, hAT-MSCs showed enhanced capacities for migration and invasion, while cell proliferation was inhibited by regulating the cell cycle by downregulating cyclins and cyclin-dependent kinases and activating the mitochondrial apoptosis pathway. In terms of glucose metabolism, our results showed mitochondrial dysfunction and elevated glycolysis of hAT-MSCs. However, interestingly, when the treated hAT-MSCs were subjected to withdrawal from HCC-CM, the alterations in phenotype and glucose metabolism could be reversed, but secretory phenotype and tumor-promoting properties appear to be permanent. Further studies showed that these changes in hAT-MSCs may be regulated by the ROS/MAPK/HIF-1α signalling pathway. Conclusion: Taken together, the effects of long-term HCC-CM treatment on phenotype and glucose metabolism in hAT-MSCs are modest and largely reversible after withdrawal, but HCC-CM endow hAT-MSCs with permanent secretory phenotype and tumor-promoting properties. This is the first report on the reversal of phenotype and glucose metabolism in tumor-associated MSCs (TA-MSCs), it is anticipated that new insights into TA-MSCs will lead to the development of novel strategies for MSC-based anti-tumor therapy.
Prevalence of musculoskeletal conditions and related disabilities in Bangladeshi adults: a cross-sectional national survey
Authors: Zahid-Al-Quadir Ahmad , Zaman Mohammad Mostafa , Ahmed Shamim , Bhuiyan Mahfuzur Rahman , Rahman Md Mujibur , Patwary Ismail , Das Bidhu Bhushan , Hossain Shaikh Amir , Paul Sujat , Shahin Abu , Rahman Mashiur , Haq Syed Atiqul
Published: September 2020

Background: Nationally representative data on burden of musculoskeletal conditions (MSK) in Bangladesh are not available. The objective of this study was to determine the prevalence of MSK conditions and related disabilities in the adult population of Bangladesh.Methods: A total of 2000 individuals aged 18 years or older were targeted from 20 primary sampling units (urban and rural) of all former seven divisions of Bangladesh in 2015. Structured interviews were done using the modified Community Oriented Program for Control of Rheumatic Disorders questionnaire to detect positive respondents. Standard criteria were used for diagnosing MSK conditions by rheumatology residents. In case of uncertainty, opinion was taken from senior rheumatologists. A Bangla version of the Health Assessment Questionnaire was used to determine disability.Results: A total of 1843 (92.1%) participated. Among them, 892 men and 951 women participated from rural (n=716) and urban (n=1127) areas. Their mean age was 40.5 (standard deviation 14.7) years. Almost a third did not have any formal schooling. Overall, 30.4% (95% confidence interval, 28.3-32.5) had MSK conditions. Low back pain (18.6%, 16.9-20.5), knee osteoarthritis (7.3%, 6.1-8.5) and soft tissue rheumatism 3.8% (2.9-4.7) were the three top-ranking MSK conditions. Rheumatoid arthritis (1.6%, 1.0-2.1), spondyloarthritis (1.2%, 7-1.8) and adhesive capsulitis (1.4%, 0.9-1.9) were relatively uncommon. Among those who had MSK conditions, 24.8% (21.3-28.6) had some degree of disability. Of them, 24.4% (21.0-28.1) had history of work loss during last 12 months. Conclusions: The high burden of MSK conditions and related disabilities in Bangladesh warrants greater attention of the health system. Further studies are needed to estimate the impact of this group of conditions particularly addressing related disabilities and loss of work.
‘Recoupling’ the attentional and motor control of preparatory postural adjustments to overcome Freezing of Gait in Parkinson’s
Authors: Maslivec Amy , Fielding Anna , Wilson Mark , Norris Meriel , Young William
Published: September 2020

Objectives: This study examined if people with Parkinson’s and freezing of gait pathology (FoG) could be trained to increase preparatory weight-shift amplitude, and facilitate step initiation during FoG. Methods: Thirty-five people with Parkinson’s and FoG attempted to initiate forward walking from a stationary position caused by a freeze (n=17, FoG-F) or voluntarily stop (n=18, FoG-NF) in a Baseline condition and two conditions where an increased weight-shift amplitude was trained via: i) explicit verbal instruction, and ii) implicit movement analogies. Results: At Baseline, weight-shift amplitudes were smaller during: i) unsuccessful, compared to successful step initiations (FoG-F group), and ii) successful step initiations in the FoG-F group compared to FoG-NF. Both Verbal and Analogy training resulted in significant increases in weight-shift amplitude in both groups, and a corresponding pronounced reduction in unsuccessful attempts to initiate stepping (FoG-F group). Conclusions: Hypometric preparatory weight-shifting is associated with failure to initiate forward stepping in people with Parkinson’s and FoG. However, impaired weight-shift characteristics are modifiable through conscious strategies. This current study provides a novel and critical evaluation of preparatory weight-shift amplitudes during FoG events. The intervention described represents an attractive ‘rescue’ strategy and should be further scrutinised regarding limitations posed by physical and cognitive deficits.
Examining aptitude and barriers to Evidence Based Medicine among trainees at an ACGME-I accredited program
Authors: Mahmoud Mai , Laws Saad , Kamal Antoun , Mohanadi Dabia Al , Mohammed Ahmed Al , Mahfoud Ziyad
Published: September 2020

Background The aims of Evidence-Based medicine (EBM) are to promote critical thinking and produces better patients’ outcome1. Accreditation Council for Graduate Medical Education (ACGME) competencies require trainees to locate, appraise and apply clinical evidence to patients’ care. Despite the emphasis that ACGME place on EBM, few organizations provide adequate training in EBM. This is even more critical in regions where medical trainees matriculate from diverse backgrounds of undergraduate medical education, where EBM may not be emphasized nor taught at all. EBM practice has a history of research in the West, however, EBM has not been widely studied in the Middle East. Methods Clinicians and trainees at Hamad Medical Corporation (HMC) matriculate from many countries in the Middle East and North Africa (MENA) and Asia. Because trainees in Graduate Medical Education (GME) come to HMC from a variety of geographic backgrounds, it is assumed that they also have a variety of experiences and aptitudes in EBM. To assess trainees EBM attitudes and knowledge in the internal medicine department at HMC in Doha, Qatar, the authors surveyed residents and fellows using a two-part survey. The first part was adapted from the evidence-based practice inventory by Kaper to assess trainees’ attitudes and perceptions of EBM. Trainees were also asked to complete the Assessing Competency in Evidence Based Medicine (ACE) tool to evaluate their aptitude in different elements of EBM. The results from the two parts were analyzed.Results The average score on the ACE tool among the participants was 8.9 (±1.6). Most participants rated themselves as beginners or intermediate in their EBM capabilities. Higher ACE scores were observed from participants with educational background from South Asia, and among those with more favorable attitudes towards EBM. Participants also reported reasonable abilities in EBM tasks and a favorable work atmosphere for EBM implementation. Lack of knowledge, resources, and time were the most reported barriers to utilizing EBM. Conclusions Earlier adoption of EBM education and practices leads to increased competence and it should be taught and evaluated in the undergraduate and GME programs. It is hoped that increased emphasis and attention to EBM at earlier stages will have an effect on overall clinician confidence and competence in utilizing EBM in the clinical setting. In a setting where matriculating clinicians arrive from heterogeneous educational backgrounds and EBM experiences, it is important to assess and continuously implement EBM training both cognitively and affectively.
SOX4 promotes the growth and metastasis of breast cancer
Authors: Zhang Jing , Xiao Chunhua , Feng Zhenbo , Gong Yun , Sun Baohua , Li Zhongqi , Lu Yimin , Fei Xiaojie , Wu Weizhu , Sun Xiaoping , Teng Lisong
Published: September 2020

Purpose

Increasing evidence has shown that the transcription factor SOX4 is closely associated with the development and progression of many malignant tumors. However, the effect of SOX4 on breast cancer is unclear. In this study, we purposed to investigate the role of SOX4 in the growth and metastasis in breast cancer and the underlying mechanism. Moreover, the effect of SOX4 on cancer cell resistance to chemotherapeutic agents was also evaluated in vitro and in vivo .

Methods

We used lentivirus technique to ectopically express SOX4 in MDA-MB-231 and SUM149 cells or knockdown SOX4 in BT474 cells, and examined the effect of these changes on various cellular functions. MTT assay was used to determine the cell viability as well as resistance to chemotherapeutic agents. The regulation of SOX4 on epithelial-mesenchymal transition (EMT)-related genes was analyzed using qRT-PCR. The binding of SOX4 to the CXCR7 gene was demonstrated using chromatin immunoprecipitation assay and dual-luciferase reporter activity assay. The effect of SOX4/CXCR7 axis on metastasis was examined using Transwell migration and Matrigel invasion assays. The expression of SOX4/CXCR7 in primary tumors and metastatic foci in lymph nodes was assessed using immunohistochemistry. Cellular morphology was investigated under phase contrast microscope and transmission electron microscopy. Moreover, the effect of SOX4 on tumor growth, metastasis, and resistance to chemotherapy was also studied in vivo by using bioluminescent imaging.

Results

SOX4 increased breast cancer cell viability, migration, and invasion in vitro and enhanced tumor growth and metastasis in vivo . It regulated EMT-related genes and bound to CXCR7 promoter to upregulate CXCR7 transcription. Both SOX4 and CXCR7 were highly expressed in human primary tumors and metastatic foci in lymph nodes. Treatment of breast cancer cells with the CXCR7 inhibitor CCX771 reversed the SOX4 effect on cell migration and invasion. Ectopic expression of SOX4 increased the susceptibility of cells to paclitaxel.

Conclusions

SOX4 plays an important role in the growth and metastasis of breast cancer. SOX4/CXCR7 may serve as potential therapeutic targets for the treatment. Paclitaxel may be a good therapeutic option if the expression level of SOX4 is high.
Traditional medicinal plants in South Tyrol (Northern Italy, Southern Alps) – Biodiversity and use
Authors: Petelka Joshua , Plagg Barbara , Säumel Ina , Zerbe Stefan
Published: September 2020

Background: Worldwide mountain regions are recognized as hotspots of ethnopharmacologically relevant species diversity. In South Tyrol (Southern Alps, Italy), and due to the region’s high plant diversity and isolated population, a unique traditional botanical knowledge of medicinal plants has flourished, which traces its history back to prehistoric times. However, changes in rural life and culture may threaten this unique biodiversity and cultural heritage. Our study aims to collect and analyze information on native plants used in traditional folk medicine, focusing on the preservation of botanical and cultural diversity.Methods: Data were collected through a review of published material that documents traditionally used medicinal plants of South Tyrol in order to capture the total diversity of plants and their usage. We evaluated different parameters, comprising the ethnobotanicity index (EI), ethnophytonomic index (EPI), relative frequency of citation (RFC), red list status, and regional legislation with regard to the plant species. Results: A total of 276 species, including 3 mushrooms and 3 lichens, were identified. These belonged to 72 families, most frequently to the Asteraceae, Rosaceae, and Lamiaceae. The most frequently cited species were Hypericum perforatum L., Urtica dioica L., and Plantago lanceolata L. According to 12 ICPC-2 disease categories, the most frequently treated human health symptoms were from the digestive and respiratory systems as well as the skin. A total of 27 species were listed as endangered, of which 16 are not protected and two are now already extinct. Among the 59 predominantly alpine species, 11 species are restricted to the high altitudes of the Alps and may be threatened by global warming. Conclusions: Our research revealed that the ethnobotanical richness of South Tyrol is among the highest in Italy and throughout the Alps. Nevertheless, it is evident that biodiversity and traditional knowledge have been heavily eroded. Furthermore, we point out particularly sensitive species that should be reconsidered for stronger protections in legal regulations.
MHC class I evolution; from Northern pike to salmonids
Authors: Grimholt Unni , Lukacs Morten
Published: September 2020

Background: Salmonids are of major importance both as farmed and wild animals. With the changing environment comes changes in pathogenic pressures so understanding the immune system of all salmonid species is of essence. Major histocompatibility complex (MHC) genes are key players in the adaptive immune system signalling infection to responding T-cells populations. Classical MHC class I (MHCI) genes, defined by high polymorphism, broad expression patterns and peptide binding ability, have a key role in inducing immunity. In salmonids, the fourth whole genome duplication that occurred 94 million years ago has provided salmonids with duplicate MHCI regions, while Northern Pike, a basal sister clade to salmonids, represent a species which has not experienced this whole genome duplication. Results: Comparing the gene organization and evolution of MHC class I gene sequences in Northern pike versus salmonids displays a complex picture of how many of these genes evolved. Regional salmonid Ia and Ib Z lineage gene duplicates are not orthologs to the Northern pike Z lineage sequences. Instead, salmonids have experienced unique gene duplications in both duplicate regions as well as in the Salmo and Oncorhynchus branch. Species-specific gene duplications are even more pronounced for some L lineage genes. Conclusions: Although both Northern pike as well as salmonids have expanded their U and Z lineage genes, these gene duplications occurred separately in pike and in salmonids. However, the similarity between these duplications suggest the transposable machinery was present in a common ancestor. The salmonid MHCIa and MHCIb regions were formed during the 94 MYA since the split from pike and before the Oncorhynchus and Salmo branch separated. As seen in tetrapods, the non-classical U lineage genes are diversified duplicates of their classical counterpart. One MHCI lineage, the L lineage, experienced massive species-specific gene duplications after Oncorhynchus and Salmo split approximately 25 MYA. Based on what we currently know about L lineage genes, this large variation in number of L lineage genes also signals a large functional diversity in salmonids.
Minimally invasive surgery for intra-articular calcaneus fractures: A 9-year, single-center, retrospective study of a standardized technique using a 2-point distractor
Authors: Rodemund Christian , Krenn Ronny , Kihm Carl , Leister Iris , Ortmaier Reinhold , Litzlbauer Werner , Schwarz Angelika , Mattiassich Georg
Published: September 2020

Background: A fracture of the calcaneus can be a painful and disabling injury. Treatment modalities may be conservative or operative. Surgical treatment strategies include open reduction and internal fixation (ORIF) techniques, as well as a variety of minimally invasive methods. The aim of this study was to evaluate the treatment options and post-treatment complication rates for intra-articular calcaneal fractures at the Traumacenter Linz over a 9-year period.Methods: All patients with calcaneal fractures treated at the Traumacenter Linz between 2007 and 2015 were included in this study. The patients records were retrospectively reviewed, and the data, including demographic parameters, cause of injury, and the time between injury and operative treatment were analyzed. The number of secondary operative interventions due to soft-tissue complications, hardware removal, and the long-term arthrodesis rate were evaluated. Results: A minimally invasive 2-point-distractor method was used in 85.8% (n=182) of all operatively managed calcaneal fractures (n=212) in our department. The majority of the operations (88.7%) were performed within two days after the accident. The secondary operation rate resulting from wound complications was 2.7% in the 2-point distractor group and 16.7% in the ORIF group. A secondary arthrodesis was performed in 4.7% (n=9) of the subtalar joints in the entire study population. Conclusions:Our data supported the assumption that severe wound complications would be less likely to occur after minimally invasive treatment compared to ORIF treatment. The rate of secondary arthrodesis in the study cohort was comparable to that in the literature.Trial Registration: Not applicable, level of evidence IV.
Significance of druggable targets (PD-L1, KRAS, BRAF, PIK3CA, MSI, and HPV) on curatively resected esophageal squamous cell carcinoma
Authors: Lee Hong Kyu , Kwon Mi Jung , Ra Yong Joon , Lee Hee Sung , Kim Hyoung Soo , Nam Eun Sook , Cho Seong Jin , Park Hye-Rim , Min Soo Kee , Seo Jinwon , Choe Ji-Young , Min Kyueng-Whan , Kang So Young
Published: September 2020

Background: Esophageal squamous cell carcinoma (ESCC) still remains intractable disease with few therapeutic options. Programmed death-ligand 1 (PD-L1), which is essential for immune evasion, is involved in the pathogenesis of ESCC and thus is a potential therapeutic target. PIK3CA, KRAS, and BRAF mutations, microsatellite instability (MSI) caused by deficient mismatch repair (dMMR), and human papillomavirus (HPV) can potentially upregulate PD-L1 expression, which might contribute to the clinical outcome of patients with ESCC. Methods: We investigated the significance of the present druggable markers [PD-L1, PIK3CA, KRAS, and BRAF mutations, MSI caused by deficient dMMR, and HPV] in 64 curatively resected ESCCs, using immunohistochemistry (PD-L1 and MMR protein expression), direct sequencing (KRAS, BRAF, and PIK3CA mutations), real-time PCR (HPV infection), and MSI using quasi-monomorphic markers. Results: PD-L1 expression, PIK3CA mutation, and MSI/dMMR were detected in 35.9%, 12.5%, and 17.2% of ESCCs, respectively. HPV was rarely detected (1.6%) (high-risk HPV68), whereas KRAS and BRAF mutations were not detected in ESCCs. PD-L1-positive tumors were not correlated with PIK3CA mutation or MSI/dMMR (all P>0.05). PD-L1, PIK3CA mutation, and MSI/dMMR characterized the patients associated with light smoking, female and younger age, and younger age and well-differentiated tumors, respectively (all P<0.05). In multivariate analysis, only PD-L1-positivity was an independent favorable prognostic factor for overall survival (OS) and disease-free survival (DFS) (P=0.023, P=0.014). In the PD-L1-negative ESCCs, PIK3CA mutation had a poor prognostic impact on both OS and DFS (P=0.006, P=0.002). Conclusions: PIK3CA mutation may be an alternative prognostic biomarker in PD-L1-negative curatively resected ESCCs that can be optional to identify high-risk patients with worse clinical outcome who require more intensive therapy and follow-up.
Dexmedetomidine versus midazolam on cough and recovery quality after partial and total laryngectomy – a randomized controlled trial.
Authors: Xu Rui , Zhu Yun , Lu Yi , Li Wen Xian , Jia Jie
Published: September 2020

Backgroundː During emergence from anesthesia after partial and total laryngectomy, excessive airway reflex and systemic hypertension may lead to subcutaneous emphysema, hemorrhage or pneumothorax. Methodsː American Society of Anesthesiologist physical status III and IV male adults undergoing elective laryngectomy were recruited and randomly allocated to receive either dexmedetomidine (group D) or midazolam (group M). The primary outcome was incidence and severity of cough. Pulse oximetry results (SpO2), heart rate (HR), systolic blood pressure (SBP), and diastolic blood pressure (DBP) were also recorded. The visual analog scale and the Ramsay sedation scale were recorded at the points of wakefulness and departure from the post-anesthesia care unit (PACU). Rescue analgesia consumption, the time of spontaneous breath recovery, duration of the PACU stay, and the incidence of adverse effects were also recorded.Resultsː The prevalence of no coughing was significantly higher in group D than in group M at the points of wakefulness and departure. HR, SBP, and DBP were significantly lower in group D compared with group M, and SpO2 was significantly higher in group D than in group M at the moment of laryngectomy. Pain scores were lower in group D than in group M. The Ramsay score at the point of wakefulness was higher in group D than in group M. There was no difference in time to spontaneous breathing recovery, duration of the PACU stay, and incidence of adverse effects.Conclusionsː Compared with midazolam, dexmedetomidine is an effective alternative to attenuate coughing and hemodynamic changes with a low incidence of adverse events during emergence from anesthesia after partial and total laryngectomy.
Effective inactivation of Nipah virus in serum samples for safe processing in low-containment laboratories
Authors: Watanabe Shumpei , Fukushi Shuetsu , Harada Toshihiko , Shimojima Masayuki , Yoshikawa Tomoki , Kurosu Takeshi , Kaku Yoshihiro , Morikawa Shigeru , Saijo Masayuki
Published: September 2020

Background: Nipah virus (NiV) is an emerging zoonotic paramyxovirus that causes severe encephalitis and respiratory disease with a high mortality rate in humans. During large outbreaks of the viral disease, serological testing of serum samples could be a useful diagnostic tool, which could provide information on not only the diagnosis of NiV disease but also the history of an individual with previous exposure to the virus, thereby supporting disease control. Therefore, an efficient method for the inactivation of NiV in serum samples is required for serological diagnosis. Methods: We determined the optimal conditions for the inactivation of NiV infectivity in human serum using heating and UV treatment. The inactivation method comprised UV irradiation with a cover of aluminum foil for 30 min and heating at 56°C for 30 min. Results: With an optimized protocol for virus inactivation, NiV infectivity in serum samples (containing 6.0 ×10 5 TCID 50 ) was completely inactivated. Conclusions: We developed a recommended protocol for the effective inactivation of NiV. This protocol would enable a regional or local laboratory to safely transport or process samples, including NiV, for serological testing in its biosafety level-2 facility.
Integrated analysis of immune-related genes in endometrial carcinoma
Authors: Wang Yiru , Liu Yunduo , Guan Yue , Li Hao , Liu Yuan , Zhang Mengjun , Cui Ping , Kong Dan , Chen Xiuwei , Yin Hang
Published: September 2020

Background: Exploring novel and sensitive targets is urgent due to the high morbidity of endometrial cancer (EC). The purpose of our study was to explore the transcription factors and immune-related genes in EC and further identify immune-based lncRNA signature as biomarker for predicting survival prognosis.Methods: Transcription factors, aberrantly expressed immune-related genes and immune-related lncRNAs were explored through bioinformatics analysis. Cox regression and the least absolute shrinkage and selection operator (LASSO) analysis were conducted to identify the immune and overall survival (OS) related lncRNAs. The accuracy of model was evaluated by Kaplan-Meier method and receiver operating characteristic (ROC) analysis, and the independent prognostic indicator was identified with Cox analysis. Quantitative real-time polymerase chain reaction (qRT-PCR) were conducted to detect the accuracy of our results.Results: A network of 29 transcription factors and 17 immune-related genes was constructed. Furthermore, four immune-prognosis-related lncRNAs were screened out. Kaplan-Meier survival analysis and time-dependent ROC analysis revealed a satisfactory predictive potential of the 4-lncRNA model. Consistency was achieved among the results from the training set, testing set and entire cohort. The distributed patterns between the high- and low-risk groups could be distinguished in principal component analysis. Comparisons of the risk score and clinical factors confirmed the four-lncRNA-based signature as an independent prognostic indicator. Last, the reliability of the results was verified by qRT-PCR in 29 cases of endometrial carcinoma and in cells.Conclusions: Overall, our study constructed a network of transcription factors and immune-related genes and explored a four immune-related lncRNA signature that could serve as a novel potential biomarker of EC.
Design and rationale of a randomized, double-blind, placebo-controlled, Phase 2/3 study evaluating dociparstat in acute lung injury associated with severe COVID-19
Authors: Lasky Joseph A. , Fuloria Jyotsna , Morrison Marion E. , Lanier Randall , Naderer Odin , Brundage Tom , Melemed Allen
Published: September 2020

Introduction: The COVID-19 Global Pandemic caused by the novel coronavirus, SARS-CoV-2, and the consequent morbidity and mortality attributable to progressive hypoxemia and subsequent respiratory failure, threaten to overrun hospital critical care units globally. New agents that address the hyperinflammatory “cytokine storm” and hypercoagulable pathology seen in these patients may be a promising approach to treat patients, minimize hospital stays, and ensure hospital wards and critical care units are able to operate effectively. Dociparstat sodium (DSTAT) is a glycosaminoglycan derivative of heparin with robust anti-inflammatory properties, with the potential to address underlying causes of coagulation disorders with substantially reduced risk of bleeding compared to commercially available heparin. Methods: This study is a randomized, double-blind, placebo-controlled, Phase 2/3 trial to determine the safety and efficacy of DSTAT added to standard of care, in hospitalized adults with COVID-19 who require supplemental oxygen. Phase 2 will enroll 12 participants in each of two dose escalating cohorts, to confirm the safety of DSTAT in this population. Following review of the data, an additional 50 participants will be enrolled. Contingent upon positive results, Phase 3 will enroll approximately 450 participants randomized to DSTAT or placebo. The primary endpoint is the proportion of participants who survive and do not require mechanical ventilation through day 28. Discussion: Advances in standard of care, recent emergency use authorizations, and positive data with dexamethasone, has likely contributed to an increasing proportion of patients who are surviving without the need for mechanical ventilation. Therefore, examining the time to improvement in the NIAID score will be essential to provide a measure of drug effect on recovery. Analysis of additional endpoints, including supportive biomarkers (e.g., IL-6, HMGB1, soluble-RAGE, D-dimer) will be performed to further define the effect of DSTAT in patients with COVID-19 infection. Trial Registration: ClinicalTrials.gov identifier NCT04389840, Registered 13 May 2020, https://clinicaltrials.gov/ct2/keydates/NCT04389840
Accuracy of remote diagnoses using intraoral scans captured in approximate true color: a pilot and validation study in teledentistry
Authors: Steinmeier Sabrina Jenny , Wiedemeier Daniel , Hämmerle Christoph HF , Mühlemann Sven
Published: September 2020

Background: Intraoral scans (IOS) provide three-dimensional images with approximate true colors representing a possible tool in teledentistry for remote examination. The aim of the present cross-sectional validation study was, therefore, to evaluate the levels of agreement between remote diagnoses derived from IOS and diagnoses based on clinical examinations for assessing dental and periodontal conditions.Methods: The test sample comprised 10 patients representing different clinical conditions. Following the acquisition of IOS (Trios, 3Shape), a full-mouth dental and periodontal examination was done and periapical radiographs were taken. Ten dentists were asked to perform dental and periodontal scorings for each of the ten patients on a tablet computer presenting the IOS. Scores included diagnosis of gingivitis/periodontitis, and evaluated presence as well as amount of plaque and calculus, and presence of teeth exhibiting gingival recession, furcation involvement, erosion, tooth wear, stain, and non-carious cervical lesion, as well as presence of decayed, filled, and crowned teeth and implants. In a second round of assessments, the periapical radiographs were provided and the dentists were able to change the scores. The time for the remote assessment was recorded. The agreement between remote and clinical scorings (reference) was then analyzed descriptively.Results: The mean time for the tele assessment was 3.17 minutes and the additional consultation of the radiographs accounted for another 1.48 minutes. The sensitivity and specificity values were 0.61 and 0.39 for gingivitis and 0.67 and 0.33 for periodontitis, with no relevant changes when radiographs were provided for the diagnosis of periodontitis (0.72 and 0.28). The agreement for dichotomized dental and periodontal indices ranged between 78 and 95%. With the provision of radiographs, the remote examiners were able to detect existing filled teeth, crowned teeth, and implants, whereas the detection of decayed teeth (70%) was not improved.Conclusions: The remote examination using IOS was effective in detecting dental findings, whereas periodontal conditions could not be assessed with the same accuracy. Still, remote assessment of IOS would allow a time-efficient screening and triage of patients. Improvement of the image quality of IOS may further allow to increase the accuracy of remote assessments in dentistry.According to the Swiss Regulation this investigation is not a clinical trial and therefore no registration in a WHO-registry is needed.
Hepatocellular carcinoma: Intratumoral EpCAM-positive cancer stem cell heterogeneity identifies high-risk tumor subtype
Authors: Krause Jenny , von Felden Johann , Casar Christian , Fründt Thorben W. , Galaski Johanna , Schmidt Constantin , Jung Caroline , Ittrich Harald , Weidemann Sören Alexander , Krech Till , Heumann Asmus , Li Jun , Fischer Lutz , Sauter Guido , Lohse Ansgar W. , Wege Henning , Schulze Kornelius
Published: September 2020

Background: The translational interest in the intratumoral heterogeneity of hepatocellular carcinoma (HCC) has been increasing. The dismal prognosis of this pathology is linked to the features of the HCC harbouring cancer stem cell (CSC), represented by EpCAM-expression. However, the extent of the impact of intratumoral distribution of CSC-features both on the recurrence after curative resection, and on clinical outcome remains unknown. To address this, we investigated the spatial heterogeneity of CSC-features with the aim of identifying the unique HCC patient subgroups amenable to adjuvant treatment.Methods: We designed a tissue microarray (TMA) from patients who had received liver resection between 2011 and 2017. Tumor specimens were sampled at multiple locations (n=3-8). EpCAM-positivity was assessed for intensity and proportion by applying a score dividing three groups: (i) negative (E-/-); (ii) heterogeneous (E-/+); and (iii) homogeneous (E+/+). The groups were further analysed with regard to time-to-recurrence (TTR) and recurrence-free-survival (RFS).Results: We included 314 tumor spots from 69 patients (76.8% male, median age 66 years, liver cirrhosis/fibrosis 75.8). The risk factors were alcohol abuse (26.2%), NASH (13.1%), HBV (15.5%), HCV (17.9%) and others (27.4%), representative of a typical Western cohort. E+/+ patients experienced significantly shorter TTR and RFS compared to E+/- (and E-/-) patients (TTR 5 vs. 19 months, p=0.022; RFS 5 vs. 14 vs. 21 months, p=0.016). Only homogeneous EpCAM-positivity correlated with higher AFP levels (>400 ng/ml, p=0.031).Conclusions: Spatial heterogeneity of EpCAM-expression was markedly present in the cohort. Of note, only homogeneous EpCAM-expression correlated significantly with early recurrence, whereas heterogeneous EpCAM-expression was associated with clinical endpoints comparable to EpCAM-negativity. We identified a unique HCC subtype associated with a high risk of tumor recurrence.
Significance of serum branched-chain amino acid to tyrosine ratio measurement in athletes with high skeletal muscle mass
Authors: Tsunekawa Katsuhiko , Matsumoto Ryutaro , Ushiki Kazumi , Martha Larasati , Shoho Yoshifumi , Yanagawa Yoshimaro , Ishigaki Hirotaka , Yoshida Akihiro , Araki Osamu , Nakajima Kiyomi , Kimura Takao , Murakami Masami
Published: September 2020

Background
Few nutritional markers reflect the hypermetabolic state of athletes with high levels of skeletal muscle. Although branched-chain amino acids (BCAA) play crucial roles in protein metabolism in skeletal muscle, the relationship between circulating BCAA concentration and skeletal muscle mass has not been fully understood. The aim of this study is to evaluate the association between skeletal muscle mass and serum BCAA to tyrosine ratio (BTR), a convenient indicator of circulating BCAA, in young Japanese men including wrestling athletes with high skeletal muscle mass.
Methods
The study enrolled 111 young Japanese men: 70 wrestling athletes and 41 controls. None were taking medications or undergoing extreme dietary restriction or an intense exercise regimen. Each participant’s body composition, serum concentrations of albumin and rapid turnover proteins including transthyretin and transferrin, BTR, and thyroid function were assessed.
Results
Compared to the controls, the athletes had significantly higher skeletal muscle index (SMI) (p < 0.001), and lower serum albumin concentration (p < 0.001) and BTR (p < 0.001). Kruskal–Wallis tests showed that serum albumin concentration and BTR were significantly lower in the participants with higher SMI. Serum albumin concentration and BTR were inversely correlated with SMI by multiple regression analysis (logarithmic albumin, β = −0.358, p < 0.001; BTR, β = −0.299, p = 0.001). SMI was inversely and transthyretin was positively correlated with serum albumin (SMI, β = −0.554, p < 0.001; transthyretin, β = 0.379, p < 0.001). Serum concentration of free 3,5,3'-triiodothyronine (FT3) was inversely correlated with BTR, and, along with SMI and albumin, was independent predictor of BTR (SMI, β = −0.321, p < 0.001; FT3, β = −0.253, p = 0.001; logarithmic albumin, β = 0.261, p = 0.003), but was not correlated with SMI or serum albumin. Serum concentrations of rapid turnover proteins were not correlated with BTR.
Conclusions
These results suggest that increased skeletal muscle mass enhances the consumption of circulating BCAAs, facilitated by thyroid hormones independently. Serum BTR may be a useful biomarker to assess the hypermetabolic state of wrestling athletes with high levels of skeletal muscle.
Scabies, Incomplete Lupus Erythematosus and Henoch-Schonlein Purpura: A Case Report
Authors: Wu Yang Fang , Wang Jing Jing , Liu Hui Hui , Chen Wei Xia , Hu Peng
Published: September 2020

Background：Henoch-Schonlein purpura (HSP) is a common autoimmune vasculitis in childhood. Although the detailed etiology of HSP remains unknown, several triggers, especially for infectious agents, have been proved to be associated with HSP onset. Case presentation: In the present report, we describe an unusual patient who suffered from HSP and incomplete lupus erythematosus (ILE) on day 8 after scabies, mainly based on nonthrombocytopenic purpura, abdominal pain, medium proteinuria, positive antinuclear antibody (ANA) and skin scrapings. A course of pulse methylprednisolone (10mg/kg/day) was administered for 6 days, followed by oral prednisone (1mg/kg/day). On day 18, the purpuric rashes almost disappeared, whereas medium proteinuria still existed. In this circumstance, a renal biopsy was performed with the informed consent of the parents. According to the criteria proposed by the International Study of Kidney Disease in Children, this patient was classified as class IIIb. The immunofluorescence microscopy revealed granular deposits of IgA, IgM and C3 in the glomerular mesangium. His proteinuria gradually decreased after treatment of corticosteroids plus mycophenolate mofetil (20mg/kg/day). Conclusions: However, it should be noted that corticosteroids and immunosuppressors may increase the relapse risk of scabies, therefore this patient should be followed up carefully after discharging from our department.
Study on Corrosion Behavior of X80 Steel under Stripping Coating by Sulfate Reducing Bacteria
Authors: Cui Yanyu , Qin Yongxiang , Ding Qingmiao , Gao Yuning
Published: September 2020

Background: At present, microorganism has been considered as important factors that threaten to buried pipelines with disbonded coatings. Aiming at the problem of unknown corrosion mechanism of sulfate-reducing bacteria (SRB), a series of studies have been carried out in this paper. Spectrophotometer and fluorescent labeling technology are used to study the growth and attachment of SRB in the simulated soil solution. The electrochemical behavior of X80 pipeline steel with or without SRB was researched by electrochemical methods such as open circuit potential, dynamic potential polarization curve, and electrochemical impedance spectroscopy. The microscopic morphology of the corrosion products on the surface of the sample was observed with a scanning electron microscope (SEM), and the element content of the corrosion products on the surface of the sample after corrosion was observed using X-ray energy spectrum (EDS) analysis. Results: The results showed that the growth and reproduction of SRB caused the pH of the soil simulated solution to increase, which promoted the corrosion of X80 steel. In addition, the cathode reaction of X80 steel in a sterile environment is the reduction of H+, and the main corrosion product is Fe oxides. When the soil simulation solution contains SRB, the cathodic reaction is controlled by both H+ reduction and sulfide depolarization reactions, and FeS appears in the corrosion products. Conclusion: Although the life cycle of SRB is only about 14 days, the corrosion of X80 steel is greatly promoted by SRB, and even causes corrosion perforation, which will bring huge economic losses and serious safety hazards.
Land use change and livestock revolution as contributors to Coronavirus emergence risk
Authors: Rulli Maria Cristina , D'Odorico Paolo , Galli Nikolas , Hayman David
Published: September 2020

The recorded number of epidemics from emerging diseases is increasing at alarming rates, posing new threats on human societies. Despite the consensus on the existence of a nexus between emerging diseases and human pressure on the environment, the link to global and regional trends in food demand and agricultural production remains poorly understood. The ongoing severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic (COVID-19) is no difference. SARS-related coronaviruses are mostly discovered in Asian horseshoe bat species. It is unclear to what extent the transmission to humans is facilitated by ongoing land use and animal husbandry trends underlying recent shifts in the food system. Forest fragmentation, human encroachment into wildlife habitats as a result of expanding urbanization, cropland, and concentrated animal farming are hypothesized to favor the emergence of zoonotic diseases. In the regions of the world populated by Asian horseshoe bats (>28.5 million km2), we analyze comprehensive high-resolution (30m-1000m) datasets on forest cover, cropland distribution, livestock density, human population, human settlements, bat species’ distribution, and land-use changes to explain why China was and remains at risk for SARS-coronavirus outbreaks. We show that in China areas populated by horseshoe bats exhibit statistically significant higher forest fragmentation and concentrations of livestock (e.g. poultry and pigs) and humans than other countries. Moreover, regions of China populated by horseshoe bats are hotspots of forest fragmentation, livestock density, and human settlements. These results are consistent with the notion that population growth and increasing meat consumption associated with urbanization and economic growth have expanded the footprint of agriculture, leading to human encroachment in wildlife habitat and increased livestock density in areas adjacent to fragmented forest patches. These results indicate that conditions in China put it at high risk for SARS-related coronavirus transmission to humans because land use patterns reduce the distance between wildlife reservoir species and humans.