bluuebunny/crossref_metadata_2025 huggingface dataset:
The First Allogeneic Transplantation of Human Umbilical Cord-derived Mesenchymal Stem/stromal Cells for Bronchopulmonary Dysplasia: Preliminary Outcomes in Four Vietnamese Infants
Authors: Thanh Liem Nguyen , Hong Thai Trieu Thi , Hong Hue Bui Thi , Hoang Van T. , Tuyet Anh Nguyen Thi , Hong Nhung Trinh Thi , Nguyen Kien T. , Hoang Duc M.
Published: July 2020

Background: Bronchopulmonary dysplasia (BPD) is a severe condition in premature infants that compromises theirlung function and necessitatesoxygen support. Despite major improvements in perinatal care minimizing the devastating effects, BPD remains the most frequent complication of extreme preterm birth. Our study reports the safety ofthe allogeneic administration of umbilical cord-derived mesenchymal stem/stromal cells (allo-UC-MSCs) and the preliminary efficacy of the treatment in four infants with established BPD.Methods: UC tissue was collected from a healthy donor, followed by propagation at the Stem Cell Core Facility at Vinmec Research Institute of Stem Cell and Gene Technology. UC-MSC culture was conducted under xeno-free and serum-free conditions. Four patients with established BPD were enrolled in this study between May 25, 2018, and December 31, 2018. All four patients received two intravenous doses of allo-UC-MSCs (1 million cells/kg patient body weight (PBW) per dose) with an intervening interval of 7 days. Safety and efficacy were evaluated during hospitalization and at 7 days and 1, 6 and 12 postdischargemonths.Results: No transplantation-associated severe adverse events or prespecified adverse events were observed in the four patients throughout the study period. At the time of this report, all patients had recovered from BPD and been weaned off of oxygen support. Chest X-rays and CT scans confirmed the dramatic reduction infibrosis.Conclusions: Allo-UC-MSC transplantation is safe and might improve respiratory function anddecrease lung fibrosis in preterm infants with established BPD.Trial registration: This preliminary study was approved by Vinmec International Hospital Ethics Board, approval number: 88/2019/QĐ-VMEC, registered 12 March 2019 - retrospectively registered.
Requirements Engineering of a Herpes Simplex Virus Patient Registry: Alpha Phase
Authors: Surodina Svitlana , Lam Ching , Grbich Svetislav , Milne-Ives Madison , Velthoven Michelle van , Meinert Edward
Published: July 2020

Background Collecting data from people with herpes simplex virus is challenging because of poor data quality, low user engagement, and concerns around stigma and anonymity. This project aimed to improve data collection for a real-world HSV registry by identifying predictors of HSV infection and selecting a limited number of relevant questions to ask new registry users in order to determine the HSV infection risk group. Methods. The US National Health and Nutrition Examination Survey (NHANES, 2015-16) database has confirmed HSV1 and HSV2 status of American participants (14-49 years) as well as a wealth of demographic and health-related data. Two datasets – for HSV1 and HSV2 – were formed using this database, and an anonymous lifestyle-data based questionnaire with a Random Forest algorithm was devised using Python. The algorithm was optimised to reduce the number of questions and to identify risk groups for HSV. Data was split into subsets to train and test the model. Results The model selected a reduced number of questions from the NHANES questionnaire that predicted HSV infection risk with high accuracy scores of 0.91 and 0.96 and high recall scores of 0.88 and 0.98 for HSV1 and HSV2 datasets, respectively. The number of questions was reduced from 150 to an average of 40, depending on age and gender, that together provides high predictability of the infection Conclusions This machine-learning algorithm for risk identification of people infected with HSV can be used in a real-world evidence registry to collect relevant lifestyle data. A current limitation is the absence of real user data and integration with electronic medical records that would enable model learning and improvement. Future work will explore model adjustments, anonymisation options, explicit permissions and standardised data schema that meet GDPR, HIPAA and third-party interface connectivity requirements.
Effects of social distancing on the spreading of COVID-19 inferred from mobile phone data
Authors: Khataee Hamid , Scheuring Istvan , Czirok Andras , Neufeld Zoltan
Published: July 2020

A better understanding of how the COVID-19 epidemic responds to social distancing efforts is required for the control of future outbreaks and to calibrate partial lock-downs. We present quantitative relationships between key parameters characterizing the COVID-19 epidemiology and social distancing efforts of nine selected European countries. Epidemiological parameters were extracted from the number of daily deaths data, while mitigation efforts are estimated from mobile phone tracking data. The decrease of the basic reproductive number (R0) as well as the duration of the initial exponential expansion phase of the epidemic strongly correlates with the magnitude of mobility reduction. Utilizing these relationships we decipher the relative impact of the timing and the extent of social distancing on the total death burden of the epidemic.
QIAstat-Dx Respiratory SARS-CoV-2 Panel Testing in Pooled Nasopharyngeal Specimens for COVID-19 Screening in a Low Prevalence Setting
Authors: Al-Hail Hamad , Mirza Faheem , Hashemi Alaa Al , Ahmad Muneera Naseer , Tang Patrick , Hasan Mohammad Rubayet
Published: July 2020

Background: COVID-19 screening in healthcare facilities plays a key role in the management of the ongoing pandemic. Rapid and reliable detection of the virus ensures early identification of cases and targeted measures to prevent transmission of the virus. QIAstat-Dx Respiratory SARS-CoV-2 Panel (QRSP) is a fully automated rapid multiplex PCR assay for common respiratory pathogens including SARS-CoV-2 that can provide sample to result in 70 minutes. However, these tests are less suitable as screening tests because of their high cost and lower throughput. Objective: In this study, we evaluated the performance of QRSP on pooled nasopharyngeal specimens to reduce the cost and improve the turn-around time (TAT) for reporting negative COVID-19 results in a low prevalence setting. Methods: Nasopharyngeal (NP) specimens were simultaneously tested by pooled QRSP (~10 specimens/pool) approach and by standard RT-qPCR, and the results were compared. TAT of reporting negative results with pooled QRSP tests were compared to that of standard testing.Results: In 208 specimens, QRSP test results with specimen pooling were in 96% agreement (Kappa=0.92; 95%CI= 0.75-1) with standard RT-qPCR. Despite pooling, CT values obtained with QRSP were correlated with that of standard RT-qPCR (Pearson correlation coefficient r=0.8343, p=0.0027). The median TAT for negative COVID-19 results by QRSP pooled approach was 2.8 hours (n=1305) compared to 5.4 hours by standard methods (n=4471).Conclusion: Pooled QRSP testing can be implemented for COVID-19 screening in low prevalence settings providing significant cost savings and improving TAT without affecting test quality.
JAK2 or CALR Mutations Status and Bone Marrow Histology in Patients with Essential Thrombocythemia in Chinese
Authors: ye xiupeng , Yimamniyaz Muhtar , LI Ye qiong , MA Jian , BAO Shen , HE Guang shen
Published: July 2020

Objectives: To characterize the clinical, and bone marrow histopathological features of essential thrombocythemia (ET) with different gene mutations status of CALR and JAK2.Methods: 159 patients of ET were centrally analyzed from January 2016 to December 2019, including 59 cases with CALR mutation, 96 JAK2 mutation, 2 MPL mutation, and 2 cases were triple-negative (TN). Bone marrow pathology observation and determination were performed by 2 immobilized experienced morphological specialists.Results: Compared to ET with JAK2 mutation, patients with CALR mutation were younger (p=0.000), showed lower count of white blood cell (WBC) and level of hemoglobin (p=0.001, p=0.001), and higher count of platelet (p=0.001). In the bone marrow (BM) biopsy, the median number of megakaryocyte and clusters of megakaryocytes in each high power field (HPF) of vision in patients with CALR mutations were lower than JAK2 mutations patients (p=0.001, p=0.001), thrombotic events in two group was different (5% vs 11.5%) (p=0.03).Conclusion: In Chinese ET patients, patients with CALR mutations were younger, and had lower levels of Hb, and count of WBC, the lower thrombotic evens although with higher platelet counts than those with JAK2 mutation. Patients with JAK2 mutations had a higher median number of megakaryocytes and median number of clusters of megakaryocytes, the clinical significance is worth exploring.
The Effect of CCCP on Mitophagy in CD4+CD25+ Regulatory T Cells in Human Peripheral Blood
Authors: Yang Yu-Jie , Karim Md Rezaul , Yuan Jang , Peng Xiao-Qian , Zeng Pei , Xu Yong , Lu Zu-Neng , Wang Yun-Fu
Published: July 2020

Objective: To investigate the effects and mechanisms of different concentrations of CCCP on mitophagy in human peripheral blood regulatory T cells. Methods: Tregs were isolated, identified, and then grouped, treating with CCCP at a concentration of 2.5 μM, 5 μM, 10 μM, 20 μM and 40 μM for 24h in an incubator. Flow cytometry detected the reactive oxygen species (ROS), mitochondrial membrane potential (MMP), mitochondrial quality, and fluorescence microscopy observed the co-localization of mitochondria and lysosomes in each group. Results: The purity of CD4+CD25+Tregs was (93.36 ± 1.87) %. With the increase of CCCP concentration, the ROS level gradually increased, while the MMP decreased gradually. About the mitochondria and lysosome fusion, the fluorescence intensity of orange (yellow) was the highest when the concentration of CCCP was in the range of 5-10 μM while decreased with the CCCP concentration continually increasing. The mitochondrial quality decreased with the increase of CCCP concentration. However, there was no significant difference between groups C, D and E. The mitochondrial quality of groups F and G were significantly lower than that of group E. Conclusions: With the concentration of CCCP gradually increased, the level of ROS in Treg cells increased, and MMP decreased, which promoted the mitophagy, mitochondrial quality maintains homeostasis. When ROS accumulated, and MMP decreased significantly, the mitophagy was inhibited, and the mitochondrial quality decreased significantly.
Covid-19 Pandemic: Application of Machine Learning Time Series Analysis for Prediction of Human Future
Authors: Chaurasia Vikas , Pal Saurabh
Published: July 2020

Purpose:Coronavirus disease is an irresistible infection caused by the respiratory disease Coronavirus 2 (SARS-CoV-2). It was first found in Wuhan, China, in December 2019, and has since spread universally, causing a constant pandemic. On June 3, 2020, 6.37 million cases were found in 188 countries and regions. Prevention is the only cure for this disease. A study was carried out on Coronavirous to observe the number of cases, deaths and recovery cases worldwide within a specific time period of five months. Based on this data, this research paper will predict the future spread of this infectious disease in human society. Methods:In our study, the data set was taken from WHO "Data WHO Coronavirus Covid-19 cases and deaths-WHO-COVID-19-global-data". This dataset contains information about the observation date, provenance/state, country/region and latest updates. In this article, we implemented several forecasting techniques: naive method, simple average, moving average, single exponential smoothing, Holt linear trend method, Holt Winter method and ARIMA, for comparison, and how these methods improve the Root mean square error score.Results:The naive method is best suited as described over all other methods. In the ARIMA model, utilizing grid search, we recognized a lot of boundaries that delivered the best-fit model for our time series data. By continuing the model, future predictions of death cases indicate that the number of deaths will increased by more than 600,000 by January 2020.Conclusion:This survey will support the government and experts in making arrangements for what is about to happen. Based on the findings of instantaneous model, these models can be adjusted to guide long time.
Characteristics and outcomes of coronavirus disease 2019 (COVID-19) patients with cancer: A single-center retrospective observational study in Tokyo, Japan
Authors: Nakamura Shohei , Kanemasa Yusuke , Atsuta Yuya , Fujiwara Sho , Tanaka Masaru , Fukushima Kazuaki , Kobayashi Taiichiro , Shimoyama Tatsu , Omuro Yasushi , Sekiya Noritaka , Imamura Akifumi
Published: July 2020

BackgroundAlthough severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has caused an international outbreak of coronavirus disease 2019 (COVID-19), data on the clinical characteristics of COVID-19 patients with cancer are limited. This study aimed to evaluate the clinical characteristics and outcomes including mortality and viral shedding period in COVID-19 patients with cancer in Japan.MethodsWe retrospectively analyzed 32 patients with a history of cancer who were referred to our hospital between January 31, 2020 and May 25, 2020. We evaluated the association between clinical outcomes and potential prognostic factors using univariate analyses.ResultsThe median age was 74.5 (range, 24–90) years and 22 patients (69%) were men. A total of 11 patients (34%) died. Our analyses demonstrated that the mortality was significantly associated with lymphocyte count, albumin, lactate dehydrogenase, serum ferritin, and C-reactive protein on admission. The median period between illness onset and the first effective negative SARS-CoV-2 PCR result was 22 days (interquartile range, 18–25) in survivors. Of four patients with hematological malignancy who developed COVID-19 within the rest period of chemotherapy, three died and the other patient, who received bendamustine plus rituximab therapy, had the longest duration of viral shedding (56 days).ConclusionOur study suggested that the risk factors for mortality previously reported in general COVID-19 patients, including lymphocytopenia, were also effective in cancer patients. Patients who received cytotoxic chemotherapy recently or were treated with chemotherapy, which can lead to lymphocyte reduction, had poor prognosis and prolonged periods of viral shedding.
Increased Interleukin-6 and Macrophage Chemoattractant Protein-1 are associated with Respiratory Failure in COVID-19
Authors: Jørgensen Marthe , Holter Jan Cato , Christensen Erik Egeland , Schjalm Camilla , Tonby Kristian , Pischke Søren Erik , Jenum Synne , Skeie Linda G , Nur Sarah , Lind Andreas , Opsand Hanne , Enersen Tone Burvald , Grøndahl Ragnhild , Hermann Anne , Dudman Susanne , Müller Fredrik , Ueland Thor , Mollnes Tom Eirik , Aukrust Pål , Heggelund Lars , Holten Aleksander Rygh , Dyrhol-Riise Anne Ma
Published: July 2020

Background: In SARS-CoV-2 infection there is an urgent need to identify patients that will progress to severe COVID-19 and may benefit from targeted treatment.Objectives: Analyze plasma cytokines in COVID-19 patients and investigate their association with respiratory failure (RF) and treatment in Intensive Care Unit (ICU). Method: Hospitalized patients (n=34) with confirmed COVID-19 were recruited into a prospective cohort study. Clinical data and blood samples were collected at inclusion and after 2-5 and 7-10 days. RF was defined as PaO2/FiO2 ratio (P/F) <40kPa. Plasma cytokines were analyzed by a Human Cytokine 27-plex assay. Measurements and Results: COVID-19 patients with RF and/or treated in ICU showed overall increased systemic cytokine levels. Plasma IL-6, IL-8, G-CSF, MCP-1, MIP-1α levels were negatively correlated with P/F, whereas combinations of IL-6, IP-10, IL-1ra and MCP-1 showed the best association with RF in ROC analysis (AUC 0.79-0.80, p<0.05). During hospitalization the decline was most significant for IP-10 (P<0.001). Conclusion: Elevated levels of pro-inflammatory cytokines were present in patients with severe COVID-19. IL-6 and MCP-1 were inversely correlated with P/F with the largest AUC in ROC analyses and should be further explored as biomarkers to identify patients at risk for severe RF and as targets for improved treatment strategies.
Randomized Control Trial For Transcranial Doppler monitoring in patients with Traumatic Brain Injury.
Authors: Fatima Nida
Published: July 2020

Traumatic Brain Injury is the leading cause of disability and mortality throughout the world. It temporarily or permanently impairs the brain function. Primary injury is induced by mechanical forces and occurs at the moment of injury while secondary brain damage may occurs hours or even days after the traumatic event. This injury may result from impairment or local decline in the cerebral blood flow. Decreases in cerebral blood flow are the result of local edema, hemorrhage or increased intracranial pressure. Although major progress has been made in understanding of the pathophysiology of this injury, this has not yet led to substantial improvements in outcome. Traumatic Brain Injury is associated with various complications including raised intracranial pressure, midline shift due to worsening of the volume of intracranial hematoma, cerebral vasospasm in traumatic sub arachnoid hemorrhage. Transcranial Doppler (TCD) has been utilized as a monitoring tool in the neurocritical care unit since it is non-invasive tool and that can be brought to bedside.However, its utility in using as a protocol in management of traumatic brain injury patients has not been studied.We hypothesized that daily TCD followed by early performance of Neuroimaging (CT scan) and Neurosurgical intervention will lead to improvement in clinical outcome.Our study’s design is Randomized Controlled Trial with neurosurgical intervention based upon the Intervention Group as the TCD-Monitoring/Neuroimaging vs Control Group as the Clinical Imaging/Neurological status. Our study’s outcome is 90 days’ clinical outcome (modified rankin scale) and Glasgow Coma Outcome Scale.
SARS-CoV-2 cytopathogenesis in cultured cells and in COVID-19 autoptic lung, evidences of lipid involvement.
Authors: Nardacci Roberta , Colavita Francesca , Castilletti Concetta , Lapa Daniele , Matusali Giulia , Meschi Silvia , Nonno Franca Del , Colombo Daniele , Capobianchi Maria Rosaria , Zumla Alimuddin , Ippolito Giuseppe , Piacentini Mauro , Falasca Laura
Published: July 2020

Background: The pathogenesis of SARS-CoV-2 remains to be defined. Elucidating SARS-CoV-2 cellular localization within cells and its cytopathic effects requires definition. We performed a comparative ultrastructural study of SARS-CoV-2 infection of Vero-6 cells and lung from COVID-19 patients. Main findings: SARS-CoV-2 induces rapid ultrastructural changes and death in Vero cells. Ultrastructural changes in SARS-CoV-2 infection differ from those in SARS-CoV-1. Type II pneumocytes in lung tissue showed prominent altered morphological features with numerous vacuoles and swollen mitochondria with presence of abundant lipid droplets. The accumulation of lipid droplets was the most striking finding we observed in cultured cells and in infected pneumocytes. Virus particles were also found associated with lipo-lysosomes suggesting that they can play an important step in virus assembly.Interpretation: The cytopathology of SARS-CoV-2 appears to be different to that caused by SARS-CoV-1. Our findings highlight important open topics which may represent future targets to contrast the pathogenicity of SARS-CoV-2.
Facilitators and Barriers to Implementation of Childhood Tuberculosis Control Program in Bangladesh: A Mixed-Methods Study from BRAC Urban DOTS Centres in Dhaka
Authors: Pantha Sandesh , Aguinaldo Ma. Jennylyn , Bari S.M. Hasan-ul , Chowdhury Sayantan , Dendup Ugyen , Gupta Rajat Das , Sutradhar Ipsita , Bari Rahamatul , Sarker Malabika
Published: July 2020

Background: World Health Organisation (WHO) estimates childhood tuberculosis (tb) in high burden countries to be at least 10-15% of all cases. Despite intensive efforts on the childhood tb control program in Bangladesh, case detection rates stand below 5%. This study investigated the implementation pathway of childhood tb in Bangladesh. The study aims to identify the factors that enable and hinder the diagnosis and treatment of childhood tb in Bangladesh.Methods: An exploratory-explanatory mixed-methods study was carried out in eight (top four and bottom four based on new case identification) urban DOTS (Directly Observed Treatment, Short-course) centres of the BRAC tb program in Dhaka Metropolitan City, Bangladesh. The study was conducted between September and December 2017. The knowledge, attitude, and practice (KAP) assessment on diagnosis and treatment of childhood tb were conducted among 111 Shasthya Shebika (SS), frontline health care workers engaged in the tb program. Field workers (n=32) and mothers of tb patients (n=4) participated in In-Depth Interviews. Key Informant Interviews (n=9) were conducted with program managers of BRAC and other key stakeholders involved in implementing the tuberculosis program in Bangladesh. Results: The survey showed a low level of knowledge on routes of transmission. The knowledge score was significantly associated with the recall of the components of training (p=0.02). Government stewardship, the presence of specific guidelines, capacity building of health workers, knowledge of frontline health workers were identified as key facilitators for the diagnosis and treatment of childhood tuberculosis. Major constraints identified included the presence of stigma, delays in seeking care, lack of diagnostic facilities, and poor engagement of private practitioners in the national tuberculosis program.ConclusionA triad of strategies including capacity building of frontline health care workers, use of recent technological advances in diagnosis, and continuous monitoring of the suspected or identified cases in the field have resulted in increased case notification of childhood tb in Bangladesh over the past few years. Frequent turnover and change of key positions in National Tuberculosis Program (NTP) and absenteeism of paediatricians in government hospitals were important barriers to implementation of childhood tb program.
Changes of Intestinal Oxidative Stress, Inflammation, and Gene Expression in Neonatal Goats Suffering from a Cold
Authors: cheng yan , Yang Chao , Tan ZhiLiang , He ZhiXiong
Published: July 2020

Background

Disease and disorders in young goats are serious threats to the animals’ health, and they influence the profitability of the goat industry. There is a need to better understand the potential biomarkers that can reflect the mortality and morbidity in young goats. Since gastrointestinal infection is probably the first ailment in young goats, the objective of this study was to explore the changes in oxidative stress, inflammation, and gene expression in the gastrointestinal tract of neonatal goats suffering from a cold.
Results

The activity of glutathione peroxidase (GSH-Px) was less (P < 0.05) in the jejunum in neonatal goats suffering from a cold compared with healthy neonatal goats. However, the malondialdehyde (MDA) activities in the jejunum and ileum were higher (P < 0.05) in neonatal goats suffering from a cold compared with healthy neonatal goats. There was no significant difference in the super-oxide dismutase (SOD) and catalase (CAT) activity observed between the two groups (P > 0.05). For the concentrations of intestinal interleukin-2 (IL2) and interleukin-6 (IL6), only the IL-2 in ileum in the neonatal goats suffering from a cold was higher than that from healthy neonatal goats. Real-time PCR results showed that the expression of most toll-like receptor-4-(TLR4) pathway-related genes was similar in the two groups. The transcriptomic analysis of the jejunum showed a total of 364 differential expression genes (DEGs) identified in neonatal goats suffering from a cold compared with healthy neonatal goats. The Kyoto Encyclopedia of Genes and Genomes (KEGG) functional enrichment analysis of up-regulated DEG was mainly related to the ECM−receptor interaction, pathways in cancer and axon guidance, and the down-regulated DEG mainly related to the arachidonic acid metabolism, complement, and coagulation cascades, and the Ras signaling pathway.
Conclusions

These results suggest that neonatal goats suffering from a cold experienced a higher intestinal oxidative stress compared with healthy neonatal goats. Thus, it is possible that the antioxidant capacity of young ruminants acts as an indicator of health status and the measurements of oxidation stress may be useful as diagnostic biomarkers, reflecting the mortality and morbidity in young goats.
Identification and Analysis of Genes Associated with Epithelial Ovarian Cancer by Integrated Bioinformatics Methods
Authors: Gui Ting , Yao Chenhe , Jia Binghan , Shen Keng
Published: July 2020

Background: Though considerable efforts have been made to improve the treatment of epithelial ovarian cancer (EOC), the prognosis of patients has remained poor. Identifying differentially expressed genes (DEGs) involved in EOC progression and exploiting them as novel biomarkers or therapeutic targets for EOC is highly valuable. Methods: Overlapping DEGs were screened out from three independent gene expression omnibus (GEO) datasets and subjected to Gene ontology (GO) and Kyoto encyclopedia of genes and genomes (KEGG) pathway enrichment analyses. The protein-protein interactions (PPI) network of DEGs was constructed in the STRING database. The top 20 hub genes were selected using cytoHubba. The expression of hub genes was detected in GEPIA, Oncomine, and human protein atlas (HPA) databases. The relationship of hub genes with the pathological stage and the overall survival and progression-free survival in EOC patients was investigated using the cancer genome atlas data. Results: A total of 306 DEGs were identified, including 265 up-regulated and 41 down-regulated. Through the PPI network analysis, the top 20 genes were screened out, among which 4 hub genes were selected after literature retrieval, including CDC45, CDCA5, KIF4A, ESPL1. The four genes were up-regulated in EOC tissues and the expression of these four genes decreased gradually with the continuous progression of EOC. Survival curves illustrated that patients with a lower level of CDCA5 and ESPL1 had better overall survival and progression-free survival. Conclusions: Two hub genes, CDCA5 and ESPL1, identified as playing tumor-promotive roles, could be utilized as potential novel therapeutic targets for EOC treatment.
Ameliorating Ribosylation-induced Aβ Pathology by Berberine via Inhibiting mTOR/p70S6K Signaling
Authors: Wang Yang-Yang , Yan Qian , Huang Zhen-Ting , Zou Qian , Li Jing , Yuan Ming-Hao , Wu Liang-Qi , Cai Zhi-You
Published: July 2020

Background: Berberine (BBR) plays a neuroprotective role in the pathogenesis of Alzheimer’s disease (AD), inhibiting β-amyloid (Aβ) production and promoting Aβ clearance. Advanced glycation end products (AGEs) promote Aβ aggregation and tau hyperphosphorylation. The activation of mTOR signaling occurring at the early stage of AD has a prominent impact on the Aβ production. This work focused on whether BBR regulates the production and clearance of ribosylation-induced Aβ pathology via inhibiting mTOR signaling.Methods: Western Blot and Immunofluorescence staining were used to detect the related proteins of the mammalian target of Rapamycin(mTOR) signaling pathway and autophagy, as well as the related kinases of Aβ generation and clearance. Tissue sections and Immunofluorescence staining were used to observe Aβ1-42 in APP/PS1 mice hippocampal. Morris water maze (MWM) test was used to measure the spatial learning and memory of APP/PS1 mice.Results: BBR improves spatial learning and memory of APP/PS1 mice. BBR limits the activation of mTOR/p70S6K signaling pathway and enhances autophagy process. BBR reduces the activity of BACE1and γ-secretase induced by D-ribose, and enhances Aβ-degrading enzymes and Neprilysin, and inhibits the expression of Aβin APP/PS1 mice.Conclusions: BBR ameliorates ribosylation-induced Aβ pathology via inhibiting mTOR/p70S6K signaling, and improves spatial learning and memory of the APP/PS1 mice.
Circular RNA circARNT2 Suppressed The Sensitivity of Hepatocellular Carcinoma Cells to Cisplatin by Targeting The miR-155-5p/PDK1 Axis
Authors: Weng Hanqin , Cao Linhui , Chen Xiaochun , Ye Liqing , Feng Weijian , Li Liping , Ye Yibiao , Wang Zaiguo
Published: July 2020

Background: Circular RNA (circRNA) is a novel subclass of noncoding-RNA molecules that participate in development and progression of a variety of human diseases via sponging microRNAs (miRNAs). Until now, the contributions of circRNAs in chemoresistance of hepatocellular carcinoma (HCC) remain largely unknown.Methods: In the present study, we aimed to investigate the role of circRNA in cisplatin resistance of HCC. We investigated the expression of circRNAs in 5 paired cisplatin-sensitive and cisplatin-resistant HCC tissues by microarray analysis. The qRT-PCR analysis was to investigate the expression pattern of circARNT2 in HCC patient tissues and cell lines. Then, the effects of circARNT2 on cisplatin resistance, cell proliferation, and apoptosis were assessed in HCC in vitro and in vivo.Results: CircARNT2 was significantly upregulated in HCC tissues and cell lines. Overexpression of circARNT2 in HCC was significantly correlated with aggressive characteristics and served as an independent risk factor for overall survival in patients with HCC. In vitro experiments showed that knockdown of circARNT2 inhibited cell proliferation and enhances the cisplatin sensitivity of HCC cells. Furthermore, circARNT2 facilitates HCC progression in vivo. We demonstrated that circARNT2 acts as a sponge for miR-155-5p and verified that PDK1 is a novel target of miR-155-5p.Conclusion: In summary, our study demonstrated that circARNT2 modulates cisplatin resistance through miR-155-5p/PDK1 pathway. Our findings indicated that circARNT2 may serve as a promising therapeutic target for overcoming cisplatin resistance for HCC.
Expression balance of ectoenzymes CD39 and CD73 predicts invasiveness in human bladder cancer
Authors: Dellê Humberto , Ferreira Janaina Mendes , Matheus Luiz Henrique Gomes , Leite Kátia Ramos Moreira , Murta Claudio Bovolenta , Claro Joaquim Francisco de Almeida , Camacho Cleber Pinto , Pontes-Júnior José
Published: July 2020

Background

An accurate prediction of progression is critical to define the management of bladder cancer (BC). The ectonucleotidases CD39 and CD73 play strategic roles in calibrating purinergic signals via an extracellular balance between ATP and adenosine. The altered expression of these enzymes plays a potential role in tumor invasion and metastasis, therefore, it has been proposed in the prognosis of solid tumors. In BC this is not yet clear. This study aimed to evaluate CD39 and CD73 expression in a cohort of patients with non-muscle-invasive (NMI) and muscle-invasive (MI) BC regard to its association with clinicopathological features.
Methods

Retrospective clinical follow-up data and primary urothelial BC specimens of 162 patients were used. Tissue microarrays were constructed, and immunohistochemistry for CD39 and CD73 was performed to make associations with clinicopathological data.
Results

Overall, 96 were NMI (59.3%) and 66 MI (40.7%). CD39 immunoreactivity in BC cells was found in 72% of the cases, while CD73 was found in 97%. High CD39 expression alone was more frequent in NMI BC (p < 0.001), while high expression of CD73 was more frequent in MI BC. The association of both markers potentiated the prediction, in that high CD39 expression and low CD73 expression was strongly associated with NMI BC and low CD39 with high CD73 was associated with MI BC.
Conclusion

The invasiveness stage of BC may be predicted by the altered expression of CD39 and CD73. Therefore CD39 serves as an additional tool for the selection of patients with favorable prognosis.
TRAF1-ALK fusion indicates poor prognosis to ALK tyrosine kinase inhibitors in relapsed/refractory ALK-positive anaplastic large-cell lymphoma patients
Authors: Pang Diwen , Huang Ling , Jiang Xinmiao , Chen Feili , Guo Hanguo , Wei Xiaojuan , Liu Sichu , Teng Yan , Liang Zhanli , Li Wenyu
Published: July 2020

Background

Relapsed/refractory (R/R) anaplastic lymphoma kinase (ALK)-positive anaplastic large cell lymphoma (ALCL) respond to ALK inhibitors, but resistance bears a poor prognosis. No biomarkers predict a long duration of response to ALK inhibitors. The ALK gene was first identified as the fusion partner of the nucleophosmin (NPM1) gene in recurrent t(2;5)(p23;q35) found in an ALCL subset. However, several distinct ALK fusions that result in highly different characteristics have also been described in lymphomas.
Methods

We retrospectively reviewed 43 patients with pathologically confirmed ALK-positive ALCL at Guangdong Provincial People’s Hospital from February 2007 through February 2020, including seven R/R patients who received ALK inhibitors (six with crizotinib and one with alectinib). We performed next-generation sequencing (NGS) with paraffin-embedded tissue for these seven R/R patients and one patient with a peripheral blood sample. We evaluated clinical characteristics and survival status.
Results

The median age of all patients was 29 (range 15–66) years. Most patients were male with advanced stage and B symptoms. The 5-year progression-free survival (PFS) and overall survival (OS) rates were 60% and 70%, respectively with a median follow-up of 52.2 (range 2.4–168.6) months. Multivariate analyses revealed that only bone marrow involvement was an independent prognostic factor for PFS (P = 0.03) and OS (P = 0.03). Of the seven R/R patients, the median line number of therapies was four (range 3–7) and that of ALK inhibitor usage was three (range 2–5). The overall response rate was 100% (n = 7). The NGS identified four patients with the NPM1-ALK fusion and two with tumor necrosis factor receptor-associated factor 1 gene (TRAF1)-ALK fusion; the latter quickly developed resistance to chemotherapy and ALK inhibitors.
Conclusions

ALK inhibitors improved survival of patients with R/R ALK-positive ALCLs. TRAF1-ALK fusion may predict a poor clinical outcome to chemotherapy and ALK inhibitors. This ALK fusion may reflect a trend toward the aggressive behavior of lymphomas.
Neurological Manifestations and Complications of Coronavirus Disease 2019 (COVID-19): A Systematic Review and Meta-Analysis
Authors: Yassin Ahmed , Nawaiseh Mohammed , Shaban Ala' , Alsherbini Khalid , El-Salem Khalid , Soudah Ola , Abu-Rub Mohammad
Published: July 2020

Background: The spectrum of neurological involvement in COVID-19 is not thoroughly understood. To the best of our knowledge, no systematic review with meta-analysis and a sub-group comparison between severe and non-severe cases has been published. The aim of this study is to assess the frequency of neurological manifestations and complications, identify the neurodiagnostic findings, and compare these aspects between severe and non-severe COVID-19 cases.Methods: A systematic search of PubMed, Scopus, EBSCO, Web of Science, and Google Scholar databases was conducted for studies published between the 1st of January 2020 and 22nd of April 2020. In addition, we scanned the bibliography of included studies to identify other potentially eligible studies. The criteria for eligibility included studies published in English language (or translated to English), those involving patients with COVID-19 of all age groups, and reporting neurological findings. Data were extracted from eligible studies. Meta-analyses were conducted using comprehensive meta-analysis software. Random-effects model was used to calculate the pooled percentages and means with their 95% confidence intervals (CIs). Sensitivity analysis was performed to assess the effect of individual studies on the summary estimate. A subgroup analysis was conducted according to severity. The main outcomes of the study were to identify the frequency and nature of neurological manifestations and complications, and the neuro-diagnostic findings in COVID-19 patients.Results: 44 articles were included with a pooled sample size of 13480 patients. The mean age was 50.3 years and 53% were males. The most common neurological manifestations were: Myalgia (22.2%, 95% CI, 17.2% to 28.1%), taste impairment (19.6%, 95% CI, 3.8% to 60.1%), smell impairment (18.3%, 95% CI, 15.4% to 76.2%), headache (12.1%, 95% CI, 9.1% to 15.8%), dizziness (11.3%, 95% CI, 8.5% to 15.0%), and encephalopathy (9.4%, 95% CI, 2.8% to 26.6%). Nearly 2.5% (95% CI, 1% to 6.1%) of patients had acute cerebrovascular diseases (CVD). Myalgia, elevated CK and LDH, and acute CVD were significantly more common in severe cases. Moreover, 20 case reports were assessed qualitatively, and their data presented separately.Conclusions: Neurological involvement is common in COVID-19 patients. Early recognition and vigilance of such involvement might impact their overall outcomes.
Predictive methodology of the probability ranges of total deaths from Coronavirus 19 (COVID-19) in China, Turkey, and Brazil
Authors: Rodríguez Javier , Prieto Signed , Rivera Carlos , Jattin Jairo
Published: July 2020

Background: A country without strategies to limit the spread of a pandemic would likely result in a dramatic increase in the number of hospitalizations and deaths. Objective: to design a methodology based on probability theory to Predict the dynamics of total deaths due to Coronavirus 19 (COVID-19) in three countries. Methods:the total number of deaths from COVID-19 was systematized, from the day the first report was made public until April 17th, 2020 in China, Turkey, and Brazil. Eight ranges were established, which have a maximum and minimum value to correlate with the total COVID-19 deaths in each of these three countries. Next, the frequency of occurrence of each range and its probability were calculated. Subsequently, these same steps were performed, but in sub-spaces of eight consecutive days. Results: the predictions gave probability values of 5.2E-43 for China, 4.4E-21 for Turkey and 7.9E-21 for Brazil. In orders of magnitude, China has a difference of 22 compared to the other two countries that have not reached the collapse of the health system that occurred in China. Additionally, the probability of the sub-spaces of these three countries reveals changes in the different ranges as the virus spreads. Conclusions: the probability values allow distinctions to be made between the dynamics of deaths from COVID-19 in different countries, additionally contributing to follow-up on pandemic mitigation interventions.
The real seroprevalence of SARS-CoV-2 in France and its consequences for virus dynamics.
Authors: Dimeglio Chloe , Loubes Jean-Michel , Miedougé Marcel , Herin Fabrice , Soulat Jean-Marc , Izopet Jacques
Published: July 2020

The SARS-CoV-2 virus has spread world-wide since December 2019, affecting millions of people and killing thousands. The recent use of serological tests to measure the effective seroprevalence of SARS-CoV-2 in the general population has led us to assess the consequences of a much lower than expected seroprevalence on the real dynamics of the virus in the population. Our prediction models assumed a 4.2% seroprevalence in Occitania and it has turned out to be only 1.3% (CI 95%: 0.6% - 2.6%, binomial method). This implies a lower than expected virus transmission rate , which may be due to infectivity varying with the patient’s symptoms or to a constraint due to an uneven population geographical distribution.
Clinical Analysis to the Cause of Hand Injuries and Its Countermeasures During the COVID-19 Outbreak and Work Resumption Period
Authors: Jin Qianjun , Zhou Haiying , lu hui
Published: July 2020

Background: Under the new circumstance of COVID-19 pandemic, a full cognition of hand injury patterns may help with the injury prevention of the factories and management of medical institutions.Methods: 38 patients were admitted to the orthopedics department with an emergent hand injury, were retrospectively collected from January 23th, 2020 to March 23,2020 . Information about demographics, type of injury, location of the injury, side of the lesion, mechanism of the injury, place where injuries occurred, surgical management and outcome was collected.Results: The number of total emergency visits of hand injury during the outbreak of COVID-19 decreased 37% from the same period of last year, and during the work resumption it had achieved an increase of 25.7%. Most of the injured patients during the stage of COVID-19 outbreak were women (60%) with a mean age of 56.7, while in the stage of work resumption were men (82.1%) with a mean age of 47.4. Most of the injury occurred at work (60.7%), and machine injury was the most frequent injury mechanism (67.9%). Fingers were the most common injured part. The majority of the injuries were classified to be minor or moderate (90%) in the outbreak, and major (42.9%) in the work resumption.Conclusion: We found an increased number of hand injuries, especially machine injury during the period of people returning to work after the outbreak of COVID-19. Medical institutions should be aware of the pattern of hand injuries during this special time in order to prepare services accordingly. Level of evidence: Level IV.
A Novel and Simply Calculated Cardiac Load Index Correlates With Coronary Artery Disease
Authors: Si Yueqiao , Fan Wenjun , Liu Jingyi , Gao Xiuxin , Han Chao , Liu Tong , Sun Lixian
Published: July 2020

Background: No cardiac load index (CLI) has been established for patients with coronary artery disease (CAD). We propose a simple method for calculating CLI and explore the association of CLI with CAD.Methods: We enrolled 4145 consecutive inpatients with suspected stable CAD from December 2011 to June 2017 at the Chengde Medical University Affiliated Hospital. All patients were divided into the CAD (n=2914) and the NCAD groups (n=1231) according to coronary computed tomography angiography. We retrospectively collected data and calculated the CLI values of all patients. The receiver operating characteristic diagnostic test analysis was performed with CLI≥77, CLI≥125, CLI≥171, CLI≥217, and CLI≥264, respectively. Multivariate logistic regression models were established to determine the risk factors of CAD. Results: The CLI was significantly higher in the CAD group than in the NCAD group and higher in the male than in the female subgroup (both P<0.001). CLI≥171 was the diagnostic cut-off value. The predictive power of CLI≥171 for CAD improved after considering other risk factors. CLI≥171 is a new independent risk factor for CAD, and is an independent risk factor for CAD in males and females (all P<0.001).Conclusions: Increased CLI is an independent risk factor for CAD, it may be used as a predictor for the prevalence for CAD to improve diagnosis and prevention.
Value of Quantitative Analysis of Left Ventricular Systolic Function in Patients on Maintenance Hemodialysis Based on Myocardial Work Technique
Authors: Liu Chang , Feng Yi-Ping , Yan Zi-Ning , Fan Li , Rui Yi-Fei , Cui Ling
Published: July 2020

Background: This study investigated the clinical value of the myocardial work technique for the quantitative analysis of left ventricular (LV) systolic function in maintenance hemodialysis (MHD) patients with or without left ventricular hypertrophy (LVH).Methods: A total of 58 MHD patients and 29 normal subjects were registered in this study. The MHD patients were divided into the non-left ventricular hypertrophy (NLVH) group (n=32) and the LVH group (n=26) according to the LV myocardial index (LVMI). Automated function imaging was used to analyze the dynamic images of the LV myocardium obtained in two-, three-, and four-chamber views. The blood pressure was inputted to generated the LV global longitudinal strain (GLS), myocardial global work index (GWI), global constructive work (GCW), global wasted work (GWW), global work efficiency (GWE), and peak strain dispersion (PSD). GLS, PSD, and the MW parameters (GWI, GCW, GWW, GWE) were compared between groups and the correlations between these parameters and the LV ejection fraction (LVEF) were examined. The receiver operating characteristic (ROC) curve was used to evaluate the efficacy of MW parameters and GLS for the assessment of LV systolic dysfunction in MHD patients with LVH.Results: The LVH group had significantly lower GWE, GWI, GCW, and GLS but higher GWW and PSD than the control and NLVH groups. Compared with the control group, the NLVH group had significantly lower GWE and GLS and higher GWW, but no significant differences in GWI, GCW, and PSD were observed between these two groups. The LVEF was negatively correlated with GWW in MHD patients, but positively correlated with GWI, GWE, and GCW. Area under the curve (AUC) analysis revealed that in the LVH group, GWE, GWW, GWI, and GCW had appreciable AUC, sensitivity, and specificity for evaluating LV function in LVH patients. Conclusion: MW parameters can be effectively used to evaluate the LV systolic function in MHD patients with or without LVH.
Synthesis and sintering of nanocrystalline Ce3+ - doped yttria nanoparticles prepared by precipitation method
Authors: Govindan Nibu Puthenpurayil , Michálková Monika , Švančárek Peter , Klement Róbert , Galusek Dušan
Published: July 2020

Cerium doped yttrium oxide (Y 1.999 Ce 0.001 O 3 , Y 1.995 Ce 0.005 O 3, Y 1.99 Ce 0.01 O 3 ) nanoparticles have been synthesized by precipitation method with ammonium hydroxide as a precipitation agent. Partly agglomerated powders with the primary size of Y 2 O 3 nanoparticles with the mean size of ~ 55 nm and cubic crystal structure were prepared. The green compacts were prepared from alcoholic suspension with PEG as a dispersant by vacuum-pressure filtration. The green bodies reached relative density over 43 % while relative density of sintered specimens (1550 °C/3 h) were in all cases close to 98 %. All sintered ceria doped samples displayed dense microstructure with closed porosity and monomodal grain size distribution. The samples exhibit light emission in the blue wavelength range, centred at 430 nm.