bluuebunny/crossref_metadata_2025 huggingface dataset:
Cardiotoxicity associated with immune checkpoint inhibitors: A retrospective analysis of patients at an academic tertiary care center
Authors: Waheed Nida , Fradley Michael G. , DeRemer David , Mahmoud Ahmad , Shah Chintan P. , Langaee Taimour Y. , Lipori Gloria P. , March Keith , Pepine Carl J. , Cooper-DeHoff Rhonda M. , Wu Yonghui , Gong Yan
Published: September 2020

Background

Immune checkpoint inhibitors (ICIs) are a novel class of anticancer agents that have demonstrated clinical response for both solid and hematological malignancies. ICIs are associated with development of immune-related adverse events including cardiotoxicity. We estimated the incidence of ICI-related cardiotoxicity in patients treated with ICIs at a large, tertiary care center.

Methods

All patients with a cancer diagnosis who received any ICI treatment in the University of Florida’s Integrated Data Repository from 2011-2017 were included. Cardiotoxicity was defined as a new ICD diagnosis code for cardiomyopathy, heart failure, arrhythmia, heart block, pericardial disease, or myocarditis after initiation of ICI treatment.

Results

Of 102,701 patients with a diagnosis of malignancy, 424 patients received at least one ICI. Sixty-two (14.6%) patients were diagnosed with at least one possible form of cardiotoxicity after initiation of ICI therapy. Of the 374 patients receiving one ICI, 21 (5.6%) developed heart failure. Of the 49 patients who received two ICIs sequentially, three (6.1%) developed heart failure and/or cardiomyopathy. Cardiotoxicity was diagnosed at a median of 63 days after initial ICI exposure. One patient developed myocarditis 28 days after receiving nivolumab. Mortality in those who developed ICI-attributable cardiotoxicity was higher compared to those who did not (66.1% vs. 41.4%, odds ratio=2.77, 1.55-4.95, p=0.0006).

Conclusions

This study suggests that the incidence of ICI-related cardiotoxicity may be higher than previously reported.
The Possibility of Contralateral Non-Sentinel Groin Node’s Metastasis in Early Primary Vulvar Cancer Women After Unilateral Sentinel Node’s Metastasis: A Single Center Evaluation in University Hospital of Düsseldorf
Authors: Winarno Andreas Suhartoyo , Mondal Anne , Martignoni Franca Christina , Fehm Tanja Natascha , Hampl Monika
Published: September 2020

Background: Sentinel node biopsy (SLNB) technique in unifocal vulvar cancer (diameter of < 4cm) and unsuspicious groin lymph nodes, the morbidity rate of patients has significantly decreased all over the world. In contrast to SLNB, bilateral inguinofemoral lymphadenectomy (IFL) has been associated with increased risk of common morbidities. Current guidelines (NCCN, ESGO, RCOG, and German) suggest that in cases of metastasis of unilateral SLNB, groin node dissection with IFL, should be performed bilaterally. However, a publication by Woelber et al. 0% (p=0/28) and Nica et al. 5.3% (p=1/19) contradicted the current guideline. Methods: A single-center analysis conducted in the University Hospital of Dusseldorf, evaluating vulvar cancer patients treated with SLNB retrospectively from 2002 to 2018. Result, discussion and conclusion: Current guideline for bilateral IFL should remain as the standard management because 22.2% women (n=4/18) had contralateral IFL groin metastasis after unilateral SLNB metastasis initially. The depth of tumor infiltrating cells was correlated significantly and positively with the incidence rate of groin metastasis (p=0.0038). Therefore, it is an indication for bilateral IFL.
Systematic Study of Single-Cell Isolation from Musculoskeletal Tissues for Single-Cell Sequencing
Authors: Guo Peng , Liu Xizhe , Zhang Penghui , He Zhongyuan , Wen Liru , Liu Shaoyu , Zhou Zhiyu , Gao Manman
Published: September 2020

Background: The single-cell platform provided revolutionary way to study cellular biology. Technologically, a sophistic protocol of isolating qualified single cells would be key to deliver to single-cell platform, which requires high cell viability, high cell yield and low content of cell aggregates or doublets. For musculoskeletal tissues, like bone, cartilage, nucleus pulposus, tendons, etc. as well as their pathological state, which are tense and dense, it’s full of challenge to efficiently and rapidly prepare qualified single-cell suspension. Conventionally, enzymatic dissociation methods were wildly used but lack of quality control. In the present study, we designed specific enzymatic treatment protocols for several human pathological musculoskeletal tissues, including degenerated nucleus pulposus, ossifying posterior longitudinal ligament and knee articular cartilage with osteoarthritis, aiming to rapidly and efficiently harvest qualified single-cell suspensions to meet the requirements of single-cell RNA-sequencing (scRNA-seq).Results: The single-cell suspensions from human degenerated nucleus pulposus and ossifying posterior longitudinal ligaments were both qualified after systematic quality control. Bioanalyzer trace showed expected cDNA size distribution of the scRNA-seq library. A clear separation of cellular barcodes from background partitions were verified by the barcode-rank plot after sequencing. However, we failed to obtain eligible samples from articular cartilage due to low cell viability and excessive cell aggregates and doublets. Conclusions: In conclusion, we provided rapid and efficient single-cell isolation protocols for human degenerated nucleus pulposus and ossifying posterior longitudinal ligament, which could be applied for scRNA-seq. More efforts will be made on improving the protocols for human articular cartilage.
Dapagliflozin Protects Doxorubicin-induced Cardiotoxicity in Breast Cancer Patients With Diabetes via Suppressing ER Stress
Authors: Chang Wei-Ting , Lin Yu-Wen , Ho Chung-Han , Chen Zhih-Cherng , Liu Ping-Yen , Shih Jhih-Yuan
Published: September 2020

Background: Cancer patients with diabetes have an increasing risk of Dox-induced cardiotoxicity. Despite previous studies reporting benefits of dapagliflozin on the cardiovascular system, it remains unknown whether dapagliflozin has a cardioprotective effect in cancer patients with diabetes receiving Dox therapy. The purpose of this study was to investigate the potential of dapagliflozin for preventing doxorubicin (Dox)-induced cardiotoxicity.Methods: Using Taiwan National Health Insurance Database, the incidence of heart failure of cancer patients with or without diabetes was investigated. Streptozotocin (STZ)-induced diabetic rats were pretreated with oral dapagliflozin (10 mg/kg/day) for 6 weeks followed by Dox (5 mg/kg/week) for 4 weeks via intraperitoneal injection. Sequential echocardiography was applied to assess cardiac function. For in vitro analysis, cardiomyocytes cultured in high glucose (30 mM) were treated with dapagliflozin at 10 M and subsequently exposed to Dox at 1 M. Apoptosis and endoplasmic reticulum (ER) stress-related protein expression were measured by immunohistochemistry and Western blotting.Results: Among the studied patients, those with diabetes had a higher risk of major adverse cardiovascular events including the development of heart failure. In diabetic rats, dapagliflozin reduced cardiac fibrosis and significantly improved cardiac function. Dapagliflozin effectively inhibited Dox-induced apoptosis and reactive oxygen species in cardiomyocytes under high glucose. Mechanistically, we showed that dapagliflozin decreased the cardiac expression of Bax and cleaved caspase 3 but increased Bcl-2. Dapagliflozin also significantly reduced ER stress-associated proteins including GRP78, PERK, eIF-2, ATF-4, and CHOP. Conclusions: Our study revealed for the first time that dapagliflozin mitigated Dox-induced cardiomyocyte apoptosis in diabetes via inhibiting ER stress. These results indicate that dapagliflozin could be useful for preventing cardiotoxicity in diabetic cancer patients receiving Dox treatment.
Periodontal Treatment by Dentistry Undergraduate Students. Assessment of the Patient's Oral Quality of Life: A Prospective Pilot Study.
Authors: Azaustre María Paloma Alvarez , Bravo Manuel , Magan-Fernandez Antonio , Rodríguez-Archilla Alberto , Llena Carmen , Mesa Francisco
Published: September 2020

Background: Our aim was to assess the impact of non-surgical periodontal treatment on oral health-related quality of life of patients with periodontitis, performed by undergraduate dental students. Methods: An observational prospective one cohort study pre‑post test was performed, involving 31 undergraduate dental students. A complete periodontal examination was performed before and after receiving non-surgical periodontal treatment. The main independent clinical variables assessed were the grade of periodontal inflammation and the number of teeth with periodontitis. Oral health-related quality of life was assessed before and after treatment through the Oral Impacts on Daily Performances (OIDP) questionnaire. The association between the extension of periodontal treatment (measured as number of treated teeth) and final OIDP score was assessed, adjusting for age, sex and baseline OIDP, in a multiple linear regression model. Results: 34 patients were enrolled and treated by the undergraduate students. The global absolute score, the mean OIDP value, was reduced from 26.2 to 12. The global percent score, percentage of impact, was reduced from 13 to 6. Non-surgical periodontal treatment showed an improvement in oral health-related quality of life. However, no association between the number of treated teeth and none of the aspects measured by ODIP was observed post-treatment, adjusting for age, sex and baseline OIDP. Conclusion: Non-surgical periodontal treatment performed by undergraduate dental students on periodontal patients, did not show any impact on oral health-related quality of life, measured by OIDP.
Insights into the Therapeutic of Glucocorticoid for Refractory Mycoplasma Pneumoniae Pneumonia in Children
Authors: Zhu Zhenli , Zhang Tongqiang , Guo Wei , Ling Yaoyao , Tian Jiao , Xu Yongsheng
Published: September 2020

Objective To observe the efficacy and safety of different doses of glucocorticoid for refractory mycoplasma pneumoniae pneumonia in children, analyze the clinical characteristics in different groups of patients, and explore the factors related to affect illness severity for children with refractory mycoplasma pneumoniae pneumonia and guide the dosage of glucocorticoids.Methods Retrospective analysis was performed on 279 children with refractory mycoplasma pneumoniae pneumonia hospitalized in our hospital between September 2018 and October 2019. 23 children were excluded, the remaining 256 children were divided into three subgroups: Group I was not given methylprednisolone (n=75), group II (n=115) was given methylprednisolone ≤125mg/d, and group III was given methylprednisolone >125mg/d (n=66). The clinical features, laboratory data, radiological manifestations between three subgroups of children were compared, relevant indicators with meaningful were used for ROC curve and multiple logistic regression analysis, and the optimal values of related factors were analyzed.Results The median age and median weight of the group III were greater than the group II（P <0.05）, the median age and median weight of the group I were greater than the group II（P <0.05）, there was no statistical significance in median age and median weight between group III and group I（P>0.05）. The group II is more serious than that of group I, and group III is more serious than that of group II, higher incidence of hypoxemia, longer fever, longer hospital stays, higher incidence of extrapulmonary complications, and more severe of radiological findings (P <0.05). The more severe presentation of disease, hormones dosage was larger, the use rate of gamma globulin was higher, the use rate of bronchoscopy was higher, and higher incidence of plastic bronchitis (P <0.05). Meanwhile, WBC, CRP, LDH, FER, D-D dimer, APTT, PLT, PCT, IL-6, ALT and the percentage of neutrophils in the three groups showed a gradual upward trend (P <0.05). In ROC curve analysis, WBC, neutrophils percentage, CRP, LDH, Fer, PCT and IL-6 can be used to distinguish RMPP with different severity and to guide the dosage of glucocorticoids. Multivariate logistic regression analysis showed that LDH 424.5IU/L, PCT 0.145ng/ml, IL-6 26.69pg/ml and lung consolidation were significant predictors for the severity of RMPP and glucocorticoids dose.Conclusions LDH 424.5IU/L, PCT 0.145 ng/ml, IL-6 26.69pg/ml and pulmonary consolidation as markers of disease severity in patients with RMPP and the dosage of glucocorticoids, which can aid in early recognition of children with severe illness, use appropriate doses of hormones, and reduce sequelae.
Development of a Fixed Repertoire of Blood Transcriptome Modules Based on Co-expression Patterns Across Immunological States
Authors: Altman Matthew , Rinchai Darawan , Baldwin Nicole , Toufiq Mohammed , Whalen Elizabeth , Garand Mathieu , Kabeer Basirudeen , Alfaki Mohamed , Presnell Scott , Khaenam Prasong , Ayllon-Benitez Aaron , Mougin Fleur , Thébault Patricia , chiche Laurent , Jourde-Chiche Noemie , Phillips Theodore , Klintmalm Goran , O'Garra Anne , Berry Matthew , Bloom Chloe , Wilkinson Robert , Graham Christine , Lipman Marc , Lertmemongkolchai Ganjana , Bedognetti Davide , Thiébaut Rodolphe , Kheradmand Farrah , Mejias Asuncion , Ramilo Octavio , Palucka Karolina , Pascual Virginia , Banchereau Jacques , Chaussabel Damien
Published: September 2020

As the capacity for generating large scale data continues to grow the ability to extract meaningful biological knowledge from it remains a limitation. Here we describe the development of a new fixed repertoire of transcriptional modules. It is meant to serve as a stable reusable framework for the analysis and interpretation of blood transcriptome profiling data. It is supported by customized resources, which include analysis workflows, fingerprint grid plots data visualizations, interactive web applications. These provide access to a vast number of module-specific functional profiling reports, reference transcriptional profiles, and give users the ability to visualize changes in transcript abundance across the modular repertoire at different granularity levels. A use case focusing on a set of six modules comprising interferon-inducible genes is also provided. Taken together, this well-characterized set of modules may be employed for the interpretation and benchmarking of blood transcriptome profiles obtained within and across patient cohorts.
Analysing the Effectiveness of Topical Bleeding Care Following Tooth Extraction in Patients Receiving Dual Antiplatelet Therapy. Personal Experiences.
Authors: Lewandowski Bogumił , Myszka Aleksander , Migut Małgorzata , Czenczek-Lewandowska Ewelina , Brodowski Robert
Published: September 2020

Background Patients using antiplatelet drugs following infarctions, acute coronary syndrome (ACS) or stroke pose a significant clinical problem if it is necessary to perform surgery, including dental surgery, since they are at risk of prolonged or secondary post-extraction bleeding. Discontinuation of this therapy is associated with a high risk of serious thromboembolic complications. The purpose of this study was to assess the effectiveness of TachoSil fibrin-collagen patches in stopping and preventing of secondary post-extraction bleeding in patients undergoing chronic antiplatelet therapy.Methods The study was conducted through retrospective examination of the medical records of 153 patients using chronic antiplatelet therapy and those qualified for tooth extraction. The largest group comprised 74 patients using aspirin and clopidogrel as dual platelet antiaggregation therapy; in this group 75 tooth extractions were carried out. In all of the patients TachoSil fibrin-collagen patches and stiches were applied to the wounds resulting from tooth removal. Results Following tooth extraction, primary bleeding was stopped in all the patients and their wounds closed via coagulation within 20-30 minutes. In eight cases, accounting for 4.9% of the patients, secondary bleeding occurred and was successfully stopped only by applying a pressure dressing soaked in tranexamic acid. Secondary bleeding occurred in three patients on the second day and in five patients on the third day following tooth removal. Conclusion Topical application of TachoSil patches following tooth removal in patients using single or dual antiplatelet therapy effectively stopped bleeding and prevented secondary bleeding after tooth extraction.
Computational Barthel Index: An Automated Tool for Assessing and Predicting Activities of Daily Living Among Nursing Home Patients
Authors: Wojtusiak Janusz , Asadzadehzanjani Negin , Levy Cari , Alemi Farrokh , Williams Allison E.
Published: September 2020

Background: Assessment of functional ability, including Activities of Daily Living (ADLs), is a manual process completed by skilled health professionals. We investigated the possibility of constructing an automated decision support tool, the Computational Barthel Index Tool (CBIT), that automatically assesses and predicts probabilities of current and future ADLs based on patients’ medical history. Methods: The data used to construct the tool include the demographic information, diagnosis codes, and reported disabilities of 181,213 residents of the Department of Veterans Affairs’ (VA) Community Living Centers. Supervised machine learning methods were applied to construct the CBIT. Temporal information about times from the first and the most recent occurrence of diagnoses was encoded. Ten-fold cross-validation was used to tune hyperparameters, and independent test sets were used to evaluate models using AUC, accuracy, recall, and precision. Random forest achieved the best model quality. Models were calibrated using isonomic regression. Results: The unabridged version of CBIT uses 578 patient characteristics and achieved average AUC of 0.94 (0.93-0.95), accuracy of 0.90 (0.89-0.91), precision of 0.91 (0.89-0.92), and recall of 0.90 (0.84-0.95) when re-evaluating patients. CBIT is also capable of predicting ADLs up to one year ahead, with accuracy decreasing over time, giving average AUC of 0.77 (0.73-0.79), accuracy of 0.73 (0.69-0.80), precision of 0.74 (0.66-0.81), and recall of 0.69 (0.34-0.96). A simplified version of CBIT with 50 top patient characteristics reached performance that does not significantly differ from full CBIT.Conclusion: Discharge planners, disability application reviewers, clinicians evaluating comparative effectiveness of treatments can use CBIT to assess and predict information on functional status of patients.
Identification and Functional Analysis of A Non-Mammalian IRF10 in Common Carp (Cyprinus Carpio. L) in The Antiviral and Antibacterial Immune Response
Authors: Zhu Yaoyao , Shan Shijuan , Zhao Huaping , Liu Rongrong , Wang Hui , Chen Xinping , Yang Guiwen , Li Hua
Published: September 2020

Background: Interferon (IFN) regulatory factors (IRFs), as the transcriptional regulatory factors play important roles in regulating the expression of type I IFN and IFN-stimulated genes (ISGs) in innate immune responses, as well as participate in cell growth, development and regulating the oncogenesis.Results: In the present study, the cDNA sequence of IRF10 was characterized in common carp (Cyprinus carpio L.) (abbreviation, CcIRF10). The predicted protein sequence of CcIRF10 shared 52.7-89.2% identities to teleost IRF10 and contained a DNA-binding domain (DBD), a nuclear localization signal (NLS) and an IRF associated domain (IAD). Phylogenetic analysis showed that CcIRF10 had a closer relationship with the IRF10 of Ctenopharyngodon idella. CcIRF10 transcripts was detectable in all examined tissues, with the highest expression in the gonad and the lowest expression level in the head kidney. The CcIRF10 expression was up-regulated in the spleen, head kidney, foregut and hindgut upon polyinosinic: polycytidylic acid (poly I:C) and Aeromonas hydrophila stimulation, and also induced by poly I:C, LPS and PGN in the peripheral blood leucocytes (PBLs) and head kidney leukocytes (HKLs) of C. carpio. In addition, overexpression of CcIRF10 was able to decrease the expressions of IFN-related genes, PKR and ISG5.Conclusions: These results indicated that CcIRF10 participated in the antiviral and antibacterial immunity, and negatively regulated the IFN response, which provided new insights into the IFN system of C. carpio.
Microbial Profile of Root Canals of Pulpally Infected Teeth In Ghanaians
Authors: Konadu Akua Boakyewaa , Nyako Ebenezer Anno , Ampofo Patrick Caldicock , Akyeh Moses Lorenzo , Ndanu Thomas Akuetteh , Yeboah-Manu Dorothy
Published: September 2020

Background Pulpal and periapical infections are initiated by microorganisms when they gain access into the dental pulp. The success of root canal treatment principally depends on the eradication of the micro-organisms in the root canal system. The aim of the study was to determine the microbial agents of infected root canals in Ghanaians patients. Methodology Forty four consecutive patients with sixty teeth referred to the Restorative Dentistry Clinic requiring root canal treatment were recruited. Root canal samples were collected from the teeth with sterile paper points. The samples were processed at the laboratory setup created at the chairside, subjected for microbial analysis and identification using Matrix-assisted laser desorption/ionization-time of flight (MALDI-TOF) mass spectrometry (MS).ResultsA total of 259 isolates were recovered from the 60 infected root canals, belonging to twenty (20) different microbial genera. Out of the 259 microbial species isolated, only two (2) were candida albicans, a fungi; 257(99.2%) were bacterial isolates belonging to 19 genera. The 19 genera had 53 bacterial species, out of which 26(49.1%) were identified as facultative anaerobes, 15(28.3 %.) as obligate anaerobes and 12(22.6%) were aerobes. Streptococcus species (Streptococcus oralis, S.mitis, S. mutans and S. constellatus) were the most predominant isolates, followed by Prevotella sp, Actinomyces sp, Enterococcus faecalis and Rothia sp respectively. ConclusionThe findings of this study show that, primary root canal infections are polymicrobial with facultative anaerobes been predominant. The determination of the microbial profile aids in understanding the pathogenesis of pulpal and periradicular infections and help in choosing effective antimicrobial irrigation and medicament for root canal treatment.
Prognostic value of circulating plasma cells in newly diagnosed multiple myeloma
Authors: Han Wenmin , Jin Yuanyuan , Xu Min , Zhao Sishu , Shi Qinglin , Qu Xiaoyan , Zhang Run , Li Jianyong , Wu Yujie , Chen Lijuan
Published: September 2020

Purpose: Multiple myeloma (MM) is a clinically and biologically heterogeneous malignancy of plasma cell. The overall survival of MM patients varies from people to people ranged from several months to decades. It is always knotty how to predict MM prognosis. The presence of circulating plasma cells (CPCs) has been associated with a worse prognosis in patients with MM.Materials and Methods: This study retrospectively analyzed CPCs in 108 cases of newly diagnosed MM patients with 8-color flow cytometry to investigate its value for outcome prediction, and combined CPCs with R-ISS to stratify the risk of MM. Results: CPCs were detected in 58/108 patients (53.7%). The optimum cutoff predicting for overall survival was determined as 0.105% by using a ROC analysis. Compared with patients with CPCs < 0.105% (n = 66，61.1%), those with CPCs ≥0.105% (n = 42, 38.9%) showed lower blood platelet count (BPC) (P=0.038), but higher β2-microglobulin (β2-MG), lactate dehydrogenase (LDH), ferritin (FER) , and harboring P53 deletion, high-risk cytogenetic abnormality, (P = 0.011, 0.001, 0.002, <0.001, and 0.020, respectively). The higher R-ISS stage seems to harbor higher CPCs. CPCs≥0.105% are independently factor for adverse outcome (P<0.001). The combination of R-ISS staging system and CPCs level was used to stratify the risk of multiple myeloma，and R-ISS III stage with CPCs ≥0.105% was ranked as a real ultra-high-risk group. Conclusion: This study suggests that high CPCs is associated with an aggressive disease and that the current R-ISS system in conjunction with CPCs may facilitate the differentiation of NDMM patients. There may also is the potential significance in modifying the definitions of high-risk disease and the practice of adopting a risk-adapted initial treatment.
Sniffer Dogs as a Screening/Diagnostic Tool for COVID-19, A Proof of Concept Study
Authors: Eskandari Esmaeil , Shiri Mahdi , Aliyazdi Helen , Farahani Ramin Hamidi , Nezami-Asl Amir , Laripour Reza , Roudgari Hassan , Moghaddam Arasb Dabbagh , Zibaseresht Ramin , Marzaleh Milad Ahmadi , Akbarialiabad Hossein , Zoshk Mojtaba Yousefi
Published: September 2020

Background: Sniffer dogs have been shown to detect certain chemical particles and to help diagnose many diseases and complications, such as colorectal cancer, melanoma, bladder cancer, and even dangerous states such as hypoglycemia in DM-1 patients. With the spread of COVID-19 throughout the world and the need to have a real-time screening of the population, especially in crowded places, this study aimed to investigate the applicability of these sniffer dogs.Methods: This study was done in two phases. In the first step, three dogs (including one German shepherd, one German black, one Labrador) were intensively trained by the classical conditioning method for seven weeks. Human specimens were obtained from the throat culture and pharyngeal secretions of both definitely positive and negative COVID-19 participants. During the first seven weeks, each dog underwent the conditioning process for averagely 1000 times. In the verification process, 80 pharyngeal secretion samples consisting of 26 positive samples of hospitalized patients and 54 negative samples of hospitalized patients for other medical reasons were provided to the training team in a single-blind manner. The verification test was done using three dogs (Lexi, Sami, and Kozhi). Another similar conditioning process was done using COVID-19 patients’ clothes and masks and the verification test was done using 50 positive and 70 negative samples by three other trained dogs (one Labrador, one Border gypsy, and one Golden retriever). Results: In the pharyngeal secretions verification test, the sniffer dogs showed 65% sensitivity and 89% specificity. In this process, they could identify 17 out of the 26 true positive samples and 48 out of the 54 true negative samples. According to the results, the positive predictive value and negative predictive value for this experiment were 74% and 84%, respectively. In the next verification test for the patients’ face masks and clothes, 43 out of the 50 positive samples were correctly identified by the dogs. Moreover, out of the 70 negative samples, 65 samples were correctly found to be negative by the canines. The sensitivity of this method was as high as 86% and its specificity was 92.9%. In addition, the positive and negative predictive values were 89.6% and 90.3%, respectively.Conclusion: Dogs are capable of being trained as the identifier of people with COVID-19 by detecting their odor and can be used as a reliable tool in limited screening.
Artemisinin attenuated oxidative stress and apoptosis by inhibiting autophagy in MPP+-treated SH-SY5Y cell
Authors: Yan Junqiang , Ma Hongxia , Lai Xiaoyi , Wu Jiannan , Liu Anran , Huang Jiarui , Sun Wenjie , Shen Mengmeng , Zhang Yude
Published: September 2020

Background
Parkinson's disease (PD) is the second most common neurodegenerative disease after Alzheimer's. The drugs currently used to treat PD cannot inhibit the development of PD, and long-term use produces severe drug resistance and adverse reaction. Artemisinin (ART) is an active ingredient of Artemisia annua and has a neuroprotective effect, but the mechanism is still unclear. This study was designed to investigate the neuroprotective effect of ART in MPP+-treated SH-SY5Y cells.
Results
There was no significant cytotoxicity when the ART concentration was under. 40 µM. The 20 µM ART for 24 h could increase the cell viability by reducing oxidative stress and cell apoptosis in MPP+-treated SH-SY5Y cell. In addition, immunoblot and immunofluorescence results showed that MPP+ treatment increased the expression of Beclin1, LC3II/LC3I and decreased the expression of P62, while ART can reverse the changes caused by MPP+.
Discussion
More and more researches reported that ART and its derivates have neuroprotective effects through anti-oxidant and anti-apoptosis. we found that pre-treated cells with 20 µM ART for 4 h could significantly increase the viability in Parkinson's disease cell model. The oxidative stress and apoptosis were the main reason for the degeneration of dopaminergic neurons, while artemisinin can attenuate oxidative stress and apoptosis in MPP+-lesioned dopaminergic neurons. The levels of autophagy proteins LC3II/I, Beclin1 and P62 also showed that MPP + increased the autophagy level, and pre-treatment with ART decreased the autophagy level, which may be the pathological mechanism for artemisinin to reduce oxidative stress damage and apoptosis.
Conclusions
These results indicate that ART exerts a positive effect on MPP+-treated SH-SY5Y cells in terms of anti-oxidative stress and anti-apoptosis. These effects may be related to autophagy. These findings contribute to a better understanding of the critical role of ART in PD treatment.
Is Peoperative Glenoid Bone Mineral Density A Risk Factor for Aseptic Glenoid Implant Loosening in Anatomic Total Shoulder Arthroplasty?
Authors: Mariaux Sandrine , Obrist Raphaël , Farron Alain , Becce Fabio , Terrier Alexandre
Published: September 2020

Background: Aseptic loosening of glenoid implants is the primary revision cause in anatomic total shoulder arthroplasty (aTSA). While supported by biomechanical studies, the impact of glenoid bone quality, more specifically bone mineral density (BMD), on aseptic glenoid loosening remains unclear. We hypothesized that lower preoperative glenoid BMD was associated with and a risk factor for aseptic glenoid implant loosening in aTSA.Methods: We retrospectively included 93 patients (69 females and 24 males; mean age, 69.2 years) who underwent preoperative non-arthrographic shoulder computed tomography (CT) scans and aTSA between 2002 and 2014. Preoperative glenoid BMD (CT numbers in Hounsfield unit) was measured in 3D using a reliable semi-automated quantitative method, in the following six contiguous volumes of interest (VOI): cortical, subchondral cortical plate (SC), subchondral trabecular, and three successive adjacent layers of trabecular bone. Univariate Cox regression was used to estimate the impact of preoperative glenoid BMD on aseptic glenoid implant loosening. We further compared 26 aseptic glenoid loosening patients with 56 matched control patients.Results: Glenoid implant survival rates were 89% (95% confidence interval CI, 81%-96%) and 57% (41%-74%) at 5 and 10 years, respectively. Hazard ratios for the different glenoid VOIs ranged between 0.998 and 1.004 (95% CI [0.996, 1.007], p≥0.121). Only the SC VOI showed significantly lower CTn in the loosening group (622±104 HU) compared with the control group (658±88 HU) (p=0.048), though with a medium effect size (d=0.42). There were no significant differences in preoperative glenoid BMD in any other VOI between patients from the loosening and control groups.Conclusions: Although the preoperative glenoid BMD was statistically significantly lower in the SC region of patients with aseptic glenoid implant loosening compared with controls, this single-VOI difference was only moderate. We are thus unable to prove that lower preoperative glenoid BMD is clearly associated with and a risk factor for aseptic glenoid implant loosening in aTSA. However, due to its proven biomechanical role in glenoid implant survival, we recommend extending this study to larger CT datasets to further assess and better understand the real impact of preoperative glenoid BMD on glenoid implant loosening/survival and aTSA outcome overall.Trial registration: Retrospectively registered
A “Full Spectrum-Domain-Time” Coalbed Gas Utilization Model and Its Application in Mining area
Authors: Linghu Jianshe , Chen Jinhua , Zhou Jianbin , Jiang Wangang
Published: September 2020

Background: As an important energy source, coalbed gas (CBG) has been widely used. However, the allocation system of CBG resources is not perfect. During the utilization process, a large amount of CBG is discharged into the air, causing environmental pollutionMethods: In this study, we proposed a “full spectrum-domain-time” CBG utilization model, including full spectrum CBG utilization technology and full domain CBG supply, In addition, based on time series algorithms, real-time prediction of the demand for CBG, grasp the characteristics of time changes in demand, and scientifically allocate resources, that is, “full-time” regulation. Taking Yangquan Coal Group, Shanxi Province, China, as a case study, introduced the application of the “full spectrum-domain-time” utilization model in the enterprise, and at last assessed the achievement of the model application. Results and Conclusions: The time series algorithm can be used to predict CBG demand in different regions of the mining area. Driven by this model, both the total CBG and low-concentration CBG utilizations in the Yangquan Coal Group increase year after year, making it promising to reach 77.15% of CBG utilization rate and indicating that application of the model has made great accomplishment.
Schlafen family member 5 (SLFN5) regulates LAT1-mediated mTOR activation in castration-resistant prostate cancer
Authors: Martinez Rafael , Salji Mark , Rushworth Linda , Ntala Chara , Blanco Giovanny Rodriguez , Hedley Ann , Clark William , Peixoto Paul , Hervouet Eric , Renaude Elodie , Kung Sonia , Galbraith Laura C. A. , Nixon Colin , Lilla Sergio , Mackay Gillian , Fazli Ladan , Sumpton David , Gleave Martin , Zanivan Sara , Blomme Arnaud , Leung Hing
Published: September 2020

Androgen-deprivation therapy (ADT) is the standard of care for the treatment of non-resectable prostate cancer (PCa). Despite high treatment efficiency, most patients ultimately develop lethal castration-resistant prostate cancer (CRPC). In this study, we perform a comparative proteomic analysis of three in vivo, androgen receptor (AR)–driven, orthograft models of CRPC. Differential proteomic analysis reveals that distinct molecular mechanisms, including amino acid (AA) and fatty acid (FA) metabolism, are involved in the response to ADT between the different models. Despite this heterogeneity, we identify SLFN5 as an AR-regulated biomarker in CRPC. SLFN5 expression is high in CRPC tumours and correlates with poor patient outcome. In vivo, SLFN5 depletion strongly impairs tumour growth in castrated condition. Mechanistically, SLFN5 interacts with ATF4 and regulates the expression of LAT1, an essential AA transporter. Consequently, SLFN5 depletion in CRPC cells decreases intracellular levels of essential AA and impairs mTORC1 signalling in a LAT1-dependent manner.
Relationship Between Tumor Mutational Burden and Maximum Standardized Uptake Value in PET (Positron Emission Tomography) Scan in Cancer Patients
Authors: Jahromi Amin Haghighat , Barkauskas Donald A , Zabel Matthew , Goodman Aaron M. , Frampton Garret , Nikanjam Mina , Hoh Carl K , Kurzrock Razelle
Published: September 2020

Purpose: Deriving links between imaging and genomic markers is an evolving field. 18F-FDG PET/CT (18F-fluorodeoxyglucose Positron Emission Tomography- Computed Tomography) is commonly used for cancer imaging, with maximum standardized uptake value (SUVmax) as the main quantitative parameter. Tumor mutational burden (TMB), the quantitative variable obtained using next-generation sequencing on a tissue biopsy sample, is a putative immunotherapy response predictor. We report the relationship between TMB and SUVmax, linking these two important parameters. Methods: In this pilot study, we analyzed 1923 patients with diverse cancers and available TMB values. Overall, 273 patients met our eligibility criteria in that they had no systemic treatment prior to imaging/biopsy, and also had 18F-FDG PET/CT within six months prior to the tissue biopsy, to ensure acceptable temporal correlation between imaging and genomic evaluation. Results: We found a linear correlation between TMB and SUVmax (p<0.001). In the multivariate analysis, only TMB independently correlated with SUVmax whereas age, gender and tumor histology did not. Conclusion: Our observations link SUVmax in readily available, routinely used, and non-invasive 18F-FDG PET/CT imaging to the TMB, which requires a tissue biopsy and time to process. Since higher TMB has been implicated as a prognostic biomarker for better outcomes after immunotherapy, further investigation will be needed to determine if SUVmax can stratify patient response to immunotherapy.
Interleukin-34 is associated with hepatocellular carcinoma in chronic hepatitis B patients
Authors: Liu Kehui , Ding Yezhou , Wang Yun , Zhao Qingqing , Yan Lei , Xie Jingdong , Liu Yunye , Xie Qing , Cai Wei , Bao Shisan , Wang Hui
Published: September 2020

Backgrounds: IL‑34 is involved in a number of auto-immunities and cancers. We explored the relationship between serum/hepatic IL‑34 and hepatitis B virus (HBV) related hepatocellular carcinoma (HBV‑HCC) patients.Methods: Serum was obtained from the HBV patients or healthy control with written consents. Liver tissue was obtained from liver biopsy in CHB, HBV related cirrhosis patients or curative resection in HBV‑HCC patients. Serum IL‑34 and MCSF were measured, using ELISA. HepaticIL‑34, MCSF and CD68 were determined, using immunohistochemistry.Results: Serum IL‑34 was 1.7, 1.6 or 1.7 fold higher in HBV‑HCC than that of the other three groups (CHB, HBV related cirrhosis, and healthy control). Serum IL‑34 was significantly reduced after trans‑hepatic arterial chemoembolization (TACE) in HBV‑HCC patients. There was significant correlation between the incidence of HBV‑HCC and IL‑34 (rs=0.160, p<0.05) as well as AFP (rs=0.442, p<0.01). Furthermore, intra-hepatic IL‑34 was higher in HBV‑HCC than that of the other three groups. Intra-hepatic IL‑34 was associated with high HBV‑DNA, HBeAg-, low tumor differentiation and small tumor size of HBV‑HCC patients. Intra-hepaticCD68+ TAMs were increased 1.6 or 1.3 fold in HBV‑HCC compared to that from CHB or HBV-cirrhosis. Intra-hepatic CD68+ TAMs were associated with high HBV‑DNA, high tumor differentiation, big tumor size, abnormal AFP and more tumor number.Conclusions: IL‑34, correlated with HBV‑HCC and IL‑34, may be used as a therapeutic target in precise medicine for management of HBV‑HCC.
A Pragmatic Trial of Active Versus Passive Teaching for Clinically Integrating Evidence Based Medicine Teaching in an Undergraduate Medical School.
Authors: Kumaravel Bharathy , Stewart Claire , Ilic Dragan
Published: September 2020

Background Clinically integrated Evidence Based Medicine (EBM) teaching promotes higher order application of knowledge, skills, and behaviours. There is, however, limited evidence on the most efficient model for clinically integrating EBM teaching. The aim of this study was to test the feasibility of integrating EBM teaching into clinical placements in an undergraduate medical school and compare the effectiveness of two different methods of EBM teaching - active teaching and passive teaching. Methods Active teaching involved blended learning methods and facilitated small group discussions. Passive teaching involved self-directed small group discussions and a remote live telecast taught session. Students’ EBM competencies were assessed using the Assessing Competency in EBM (ACE tool) and Educational Prescriptions (EP) and in summative final professional written and clinical examinations.Results Education was delivered to 65 students, of whom 45 received active teaching, while 20 received passive teaching. Students receiving active teaching performed better in EPs (MD=-2.28, -4.31, -0.26). There was no significant difference in performances in the ACE tool (MD=-1.02, -2.20, 0.16); the written final professional exams (MD=-0.11, -0.65, 0.44) and the EBM OSCE stations (MD=-0.81, -2.38, 0.74). Conclusions It was feasible to integrate EBM teaching into clinical placements in an undergraduate medical school. Both active and passive methods were effective in delivering EBM teaching. While students in the active teaching model scored higher in EPs; there was no significant difference in performances in the ACE tool or the summative assessments. Scaffolding student learning or a spiral approach to EBM teaching model provides a great example of continually shifting the zone of proximal development.
Depression, Anxiety and Stress Symptomatology among Swedish University Students Before and During the COVID-19 Pandemic: A Cohort Study.
Authors: Johansson Fred , Côté Pierre , Hogg-Johnson Sheilah , Rudman Ann , Holm Lena W. , Grotle Margreth , Jensen Irene , Sundberg Tobias , Edlund Klara , Skillgate Eva
Published: September 2020

Background. The COVID-19 pandemic has had a profound effect on societies, economies, and daily life of citizens worldwide. This has raised important concerns about the mental health of different populations. We aimed to determine if symptom levels of depression, anxiety, and stress were different during the COVID-19 outbreak compared to before, with the Depression, Anxiety and Stress Scale as main outcome. We also aimed to determine whether pre-pandemic loneliness, poor sleep quality and mental health problems were associated with worse trajectories of mental health. Methods. We conducted a cohort study with 1658 Swedish university students answering questionnaires before the pandemic and a 81 % response-rate to follow-ups during the pandemic. Generalized Estimating Equations were used to estimate mean levels of symptoms before and during the pandemic, and to estimate effect modification by levels of loneliness, sleep quality and pre-existing mental health problems. Results. We found small differences in symptoms. Mean depression increased by 0.23/21 (95% CI:0.03 to 0.43), mean anxiety decreased by -0.06/21 (95% CI: -0.21 to 0.09) and mean stress decreased by - 0.34/21 (95% CI: -0.56 to -0.12). Loneliness, poor sleep quality and pre-existing mental health problems minimally influenced trajectories. Conclusions. Contrary to widely held concerns, we found minimal changes in mental health among Swedish university students during the first months of the COVID-19 pandemic.
Novel method to achieve crystallinity of calcite by Bacillus subtilis in coupled and non-coupled calcium-carbon sources
Authors: Ferral-Pérez Héctor , Galicia-García Mónica , Alvarado-Tenorio Bonifacio , Izaguirre-Pompa Aldo , Aguirre-Ramírez Marisela
Published: September 2020

Bacteria mineralization is a promising biotechnological approach to apply in biomaterials development. In this investigation, we demonstrate that Bacillus subtilis 168 induces and influences CaCO3 composites precipitation. Crystals were formed in calcium-carbon non-coupled (glycerol + CaCl2, GLY; or glucose + CaCl2, GLC) and coupled (calcium lactate, LAC; or calcium acetate, ACE) agar-sources, only maintaining the same Ca2+ concentration. The mineralized colonies showed variations in morphology, size, and crystallinity form properties. The crystals presented spherulitic growth in all conditions, and botryoidal shapes in GLC one. Birefringence and diffraction patterns confirmed that all biogenic carbonate crystals (BCC) were organized as calcite. The CaCO3 in BCC was organized as calcite, amorphous calcium carbon (ACC) and organic matter (OM) of biofilm; all of them with relative abundance related to bacteria growth condition. BCC-GLY presented greatest OM composition, while BCC-ACE highest CaCO3 content. Nucleation mechanism and OM content impacted in BCC crystallinity.
Cardiac arrest after small doses ropivacaine: Local Anesthetic Systemic Toxicity in the course of continuous femoral nerve blockade
Authors: Gola Wojciech , Bialka Szymon , Zajac Marek , Smereka Jacek , Szarpak Lukasz
Published: September 2020

Background: The paper presents a case report of an episode of local anesthetic systemic toxicity (LAST) with cardiac arrest after continuous femoral nerve blockade in a 74-year-old female patient after elective total knee replacement surgery. Case presentation: A 74-year-old patient burdened with hypertension, osteoarthritis, underwent elective total knee replacement surgery (TKR). After surgery, a continuous femoral nerve blockade was performed and an infusion of a local anesthetics (LA) was started using an elastomeric pump. Five hours after surgery, the patient had an episode of generalized seizures followed by cardiac arrest. After resuscitation, spontaneous circulation was restored and the patient was transferred to the Intensive Care Unit. 20% lipid emulsion was used in the treatment. On day 2 of the ICU stay, the patient was fully cardiovascularly and respiratorily stable without neurological deficits and was discharged to the orthopedic department to continue treatment. Conclusion: Systemic toxicity of LA is a serious and potentially fatal complication of the use of LA in clinical practice. The incidence of LAST is underestimated, although in recent years there has been a significant decrease in the incidence of this serious complication. It should be noted that in nearly 40% of patients, LAST deviates from the classic and typical course and may have an atypical manifestation, and the first symptoms may appear with a long delay, especially when continuous blockades are used. Therefore, proper supervision of the patient and the developed procedure in the event of LAST is undoubtedly important here. If the first serious symptoms of LAST appear, current guidelines recommend early application of 20% lipid emulsion.
Relationship between anxiety and abnormal behavior in children with asthma in Lanzhou, China
Authors: Shi Daiyu , Li Guirong , Li YuanLin , Zhang RongFang , Na Feiyang , Gao Wenlong
Published: September 2020

Background: Asthma can increase the risk of anxiety and abnormal behavior among children but the correlation between anxiety and behavioral abnormalities in children with asthma was unclear. Methods: The Self-Rating Anxiety Scale and the Rutter Children’s Behavior Questionnaire were used to conduct surveys with 337 children aged 6 to 14 years who were diagnosed in the asthma clinic of Gansu Provincial Maternity and Child Care Hospital in Lanzhou, China from January to December 2019. SPSS 22.0 software was used to perform multivariate logistic regression and factor analysis on the items of the anxiety scale to extract different anxiety manifestations. Results: The abnormal behavior rate was 37.1% among the 337 investigated children with asthma. A total of 3 factors were extracted by factor analysis on the 20 items of the anxiety scale, namely mental, sensory, and hand-and-foot manifestations. The 3 factors were divided into 3 groups using tertiles (Q1~Q3). After controlling for sex, age, wheezing history, marital status of parents, caregiver awareness, and caregiver’s home care situation, compared with Q1, the multivariate logistic regression model showed that Q3 had a statistically significant relationship with abnormal behavior, regardless of mental or hand-and-foot manifestation. No connection between Q2 and behavior abnormalities was found. For sensory manifestations, neither Q3 nor Q2 was significantly related to abnormal behavior. Conclusions: Abnormal behavior was related to only severe anxiety among children with asthma. Therefore, psychological intervention should be carried out as early as possible in the treatment of children with asthma to prevent and correct abnormal behavior.
Complications of COVID-19 , a case with both neurological and dermatological complications.
Authors: davoodian parivash , korani setayesh sotoudehnia , roudkoli ali rezazadeh , ouspid elham
Published: September 2020

Recently, different complications and clinical manifestations of COVID-19 have been reported such as neurological or dermatological complications, We present a confirmed COVID-19 case of diplopia and ophthalmoplegia presenting skin lesions at the same time .