bluuebunny/crossref_metadata_2025_split huggingface dataset:
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

Abstract
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

Abstract
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

Abstract
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

Abstract
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

Abstract

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

Abstract
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

Abstract
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

Abstract
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

Abstract
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

Abstract
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

Abstract
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.