bluuebunny/crossref_metadata_2025_split huggingface dataset:
Cynandione A alleviates neuropathic pain through spinal microglial interleukin-10/β-endorphin expression following α7 nicotinic acetylcholine receptor activation
Authors: Han Qiao-Qiao , Yin Min , Wang Zi-Ying , Liu Hao , Ao Jun-Ping , Wang Yong-Xiang 
Published: July 2020

Abstract
Background

Cynandione A, an acetophenone isolated from Cynanchum Wilfordii Radix, exhibits antihypersensitivity effects in neuropathic pain. This study sought to explore the target molecule and mechanisms underlying cynandione A mechanical antiallodynia, particularly related to the spinal glial expression of IL-10/β-endorphin, cAMP/PKA/p38/CREB signaling and α7 nicotinic acetylcholine receptor (α7 nAChR) activation.
Methods

IL-10 and β-endorphin in the spinal cord of spinal nerve ligation-induced neuropathic pain rats and cultured primary microglia were assessed by qRT-PCR and ELISA assays. Double immunofluorescence staining of IL-10, β-endorphin with glial and neuronal cellular biomarkers was also conducted in the spinal cord and cultured primary microglia. Microglial phosphorylation of PKA, p38, CREB and STAT3 were detected using western blot.
Results

Cynandione A significantly attenuated mechanical allodynia in neuropathic rats and substantially increased IL-10 and β-endorphin (but not dynorphin A) expression in the spinal cords and cultured primary microglia. The IL-10 antibody attenuated cynandione A-induced spinal or microglial gene expression of β-endorphin and mechanical antiallodynia, whereas the β-endorphin antiserum blocked cynandione A-induced mechanical antiallodynia but not spinal or microglial IL-10 gene expression. The α7 nAChR antagonist methyllycaconitine significantly declined cynandione A-induced mechanical antiallodynia and spinal or microglial expression of IL-10 and β-endorphin. Cynandione A stimulated microglial phosphorylation of PKA, p38 and CREB, which was inhibited by methyllycaconitine. Treatment with the adenylyl cyclase inhibitor DDA, PKA inhibitor H-89, p38 inhibitor SB203580 and CREB inhibitor KG501 attenuated cynandione A-induced mechanical antiallodynia and spinal or microglial expression of IL-10 and β-endorphin. Cynandione A stimulated spinal phosphorylation of the transcription factor STAT3, which was inhibited by methyllycaconitine, H-89 and the IL-10 antibody. The STAT3 inhibitor NSC74859 weakened cynandione A-induced mechanical antiallodynia and spinal expression of β-endorphin.
Conclusion

Our results illustrate that cynandione A produces mechanical antiallodynia through spinal microglial expression of IL-10 via the cAMP/PKA/p38/CREB signaling and subsequent β-endorphin expression via the IL-10/STAT3 signaling, following α7 nAChR activation.
Pinin promotes tumor progression via PI3K/AKT/CREB signaling pathway in prostate cancer
Authors: Meng Xiang-yu , Zhang Hui-zhi , Ren Yi-yue , Wang Ke-jie , Chen Jun-feng , Su Rui , Jiang Jun-hui , Wang Ping , Ma Qi 
Published: July 2020

Abstract
Background

Pinin (PNN), a desmosome associated protein, was demonstrated to be over-expressed and act as a tumor-promoting factor in ovarian cancer, hepatocellular carcinoma and colorectal cancer. However, the precise role of PNN in prostate cancer is still unknown.
Methods

The expression levels of PNN were assessed in prostate cancer by qRT-PCR, western blotting and immunohistochemical staining. The other proteins were quantified by western blotting. PNN-depleted cells were produced by infecting with lentivirus bearing short hairpin RNAs against PNN. PNN over-expression was performed by transfecting PNN expression vector. The proliferation of each cell line was assessed by MTS and colony formation assays. Tumors were induced on nude mice by injecting tumor cells subcutaneously. Apoptosis and cell cycle were evaluated by flow cytometry. Transwell and wound healing assay were performed to determined the ability of cell invasion and migration. The TCGA data were analyzed with GEPIA (Gene Expression Profiling Interactive Analysis) and GraphPad Prism.
Results

Here, we reported that PNN was upregulated in prostate cancer tissues and PNN expression was positively associated with Gleason score, tumor stage and tumor metastasis. PNN promoted cell growth and tumorigenicity in vitro and in vivo, and might modulate cell growth through driving G1/S transition via CDK6, CDK2, and Cyclin D1 in prostate cancer cells. Furthermore, PNN accelerated cell invasion, migration and EMT processes of prostate cancer cells accompanied with the up-regulation of MMP-2, MMP-9, N-cadherin, Vimentin and down-regulation of E-cadherin. Mechanism study demonstrated that the proliferation- and motility-promoting effects of PNN on prostate cancer cells dependent on the activation of PI3K/AKT/CREB signaling, which was reversed by AKT and CREB inhibitors.
Conclusions

Collectively, these findings indicated that PNN plays important roles in prostate cancer tumorigenesis and progression and it may be a potential therapeutic target for prostate cancer treatment.
Incidence, Outcomes and Risk Factors of Heparin-Induced Thrombocytopenia after Total Joint Arthroplasty: An Analysis of the National Inpatient Sample Database
Authors: Chen Yuhang , Wang Jian , Shi Zhan-jun , Zhang Yang , Yang Qinfeng , Xu Yichuan 
Published: July 2020

Abstract
Background

Heparin-induced thrombocytopenia (HIT) is a severe immune-mediated complication of heparin exposure, leading to negative consequences after total hip (THA) and knee arthroplasty (TKA). However, the incidence and risk factors of HIT remain to be elucidated. This study aimed to identify the incidence, outcomes, and risk factors of HIT after THA and TKA.

Methods

A retrospective study was conducted using the National Inpatient Sample (NIS) database from 2005 to 2014. The incidence and outcomes of HIT after THA or TKA were documented. Logistic regression analysis was performed to identify the postoperative HIT risk factors.

Results

A total of 593,045 patients who underwent THA and 1,228,707 patients who underwent TKA were identified. The cumulative incidences were 0.02% and 0.01%, respectively. The HIT group presented significantly higher Charlson Comorbidity Index (CCI) and Elixhauser Comorbidity Index (ECI) scores, longer hospital stays (LOS), and higher medical costs. HIT led to a significantly higher mortality rate after THA (2.17% vs. 0.16%, p =0.0091). Although not statistically significant, the HIT mortality rate after TKA was also increased (0.58% vs. 0.07%; p =0.1178). In THA, the risk factors of HIT were racial minority, AIDS, pulmonary circulation disorders (PCD), psychoses, and hypertension; the protective factors were large-scale and teaching hospitals. In TKA, the HIT risk factors were racial minority, PCD, and weight loss. Teaching hospitals served as protective factors.

Conclusions

The incidence of HIT after THA and TKA is relatively low; however, HIT significantly increases inpatient mortality, LOS, and medical cost. Therefore, HIT warrants considerable attention and further investigation.
The impact of down-regulation on obstetrics and perinatal outcomes in singleton pregnancies after IVF: a retrospective cohort study
Authors: Dong Xiyuan , Zheng Yu , Chen Biao , Wang Lan , Jin Lei , Ai Jihui 
Published: July 2020

Abstract
Background Down-regulation has been widely used in IVF treatment; however, it lacks reports on the impact of down-regulation on obstetrics and perinatal outcomes. The purpose of this study is to evaluate the effect of down-regulation on obstetrics and perinatal outcomes. Methods This is a retrospective cohort study on 3578 patients achieving singleton pregnancy after their first IVF attempt. The patients were grouped by the serum estradiol after down-regulation (E2D) into three groups: <30, 30-55, >55pg/ml. The cumulative live-birth rate, obstetrics and pediatric results were main outcome measures. General linear models and Chi-square test were performed for statistical analysis. Results The patients with E2D <30, 30-55, >55pg/ml had similar cumulative live-birth rate. The patients with E2D <30pg/ml had a lower risk for hypertension disorders than those with E2D 30-55pg/ml. No difference was found in the prevalence of placenta previa, placenta abruption, premature rupture of membrane, hemorrhage, gestational diabetes mellitus, or intrauterine growth restriction. The newborns of patients with E2D <30pg/ml had a lower risk for PICU attempt than those with E2D >55pg/ml. There was no difference in congenital anomaly or mortality rate. Conclusion We found no effect of down-regulation on cumulative live-birth rate. The patients with E2D<30pg/ml may have advantages in lower risks for maternal hypertension and newborns PICU attempt.
Sensitivity evaluation of 2019 novel coronavirus (SARS-CoV-2) RT-PCR detection kits and strategy to reduce false negative
Authors: Zhou Yunying , Pei Fengyan , Wang Li , Zhao Huailong , Li Huanjie , Ji Mingyu , Yang Weihua , Wang Qingxi , Zhao Qianqian , wang yunshan 
Published: July 2020

Abstract
Background: In absence of effective vaccines, infection prevention and control of SARS-CoV-2 through diagnostic testing and quarantine is critical. Early detection and differential diagnosis of respiratory infections increases the chances for successful control of COVID-19 disease. The nucleic acid RT-PCR test is regarded as the current standard for molecular diagnosis with high sensitivity. However, the highest specificity confirmation target ORF1ab gene is considered to be less sensitive than other targets in clinical application. In addition, a large amount of recent evidence indicates that the initial missed diagnosis of asymptomatic patients with SARS-CoV-2 and discharged patients with “re-examination positive” may be due to low viral load, and the ability of rapid mutation of SARS-CoV-2 also increases the rate of false negative results. Moreover, the current used mixed sample nucleic acid detection is helpful to seek out the early community transmission of SARS-CoV-2, but the detection kit needs ultra-high detection sensitivity. Methods: From January to March 2020, 10 confirmed specimens of 2019-nCoV were recruited from three 2019-nCOV nucleic acid testing center. Five different amplification kits with three different primers and probes sources were selected. RT-PCR and continuous amplification of nasopharyngeal and oropharyngeal swabs and environmental specimens were performed to validate the sensitivity of the commercially available Nucleic acid test kits. Results: The results showed that ORF1ab gene can still be reported as positive at 1:10 dilution and the N gene even at 1:40 dilution with kit-1 through the verification of multiple positive samples, While other kits have less sensitive. The results in the suspicious range of weakly positive nasopharyngeal and oropharyngeal swabs and environmental specimens could be reported as positive after another re-amplification.Conclusions: Through evaluate the sensitivity of different nucleic acid detection kits, this study provide direct evidence for the selection of kits for mixed sample detection or make recommendations for the selection of validation kit, which is of great significance for the prevention and control of the current epidemic and the discharge criteria of low viral load patients.
Virus discharge and initial gastrointestinal involvement are negatively associated with circulating lymphocyte count in COVID-19
Authors: Chen Wei , Zheng Kenneth I. , Liu Saiduo , Xu Chongyong , Xing Chao , Qiao Zengpei 
Published: July 2020

Abstract
Background: It’s reported SARS-CoV-2 could transmit via gastrointestinal tract, with or without pulmonary symptoms. However, as far as we know, there is no convenient marker to predict the virus discharge in stool and initial gastrointestinal involvement of COVID-19.Aims: We aimed to investigate the biomarker predicting virus discharge in stool and initial gastrointestinal involvement of COVID-19, which may assist the clinicians to better combat and prevent COVID-19.Methods: The patients complained of initial gastrointestinal involvement, including vomiting, diarrhea, with or without respiratory symptoms, attending the Sixth People’s Hospital of Wenzhou, and the Second Affiliated Hospital of Wenzhou Medical University, were screened by qRT-PCR for SARS-CoV-2. The Confirmed COVID-19 patients without contaminated ingestion were all enrolled to investigate the association between circulating lymphocyte count and virus discharge, initial gastrointestinal involvement.Results: 76 COVID-19 patients were finally enrolled in this study (mean age 44.5, male 44.7%), with 24 (31.5%) complained of initial gastrointestinal symptoms. Significantly lower circulating lymphocyte count was found in the patients with positive results of qRT-PCR on stool (p = 0.012). Furthermore, when the circulating lymphocyte count increased from bottom tertile to the 2nd and 3rd tertiles, the risk of initial gastrointestinal involvement decreased by nearly 75% (OR = 0.25, 95% CI: 0.07, 0.98, p = 0.047), 83% (OR = 0.17, 95% CI: 0.05, 0.63, p = 0.008), adjusted for possible confounders.Conclusions: The circulating lymphocyte count is negatively associated with virus discharge in stool in COVID-19 patients, and the risk of initial gastrointestinal involvement also.
Medical students’ mood adversely affected by COVID-19 pandemic: An interim analysis from the SPICE-19 prospective cohort study of 2075 medical students and interim foundation doctors
Authors: Bandyopadhyay Soham , Georgiou Ioannis , Baykeens Bibire , Gillespie Conor S , Crespo Marta de Andres , Bashir Mohammad Talha , Handa Ashok , Saunders Kate E A 
Published: July 2020

Abstract
Background:Currently, we can only speculate on what the effects of the COVID-19 pandemic have been on medical students and interim foundation year doctors. In order to support them appropriately both now and, in the future, it is imperative that we understand the impact it has had upon them. This study assessed the effects of the COVID-19 pandemic on medical students and interim foundation year doctors across the United Kingdom (UK), and the support that they received and sought. Methods:A prospective, observational, multicentre study was conducted. All medical students and interim foundation year doctors were eligible to participate. The data analysis was carried out as detailed a priori in the protocol. Findings:A total of 2075 individuals participated in the SPICE-19 survey from 33 medical schools. There was a significant (p < 0.0001) decrease in participants’ mood when comparing their mood before the pandemic to during the pandemic. Social distancing and more time at home/with family were the factors that negatively and positively respectively impacted the mood of the greatest number of participants. All areas of life included in the survey were found to have been significantly more negatively impacted than positively impacted (p < 0.0001). 931 participants wanted more support from their university. Participants were mainly seeking support with exam preparation, course material, and financial guidance. Discussion:Medical and foundation schools need to prepare adequate and effective support. If no action is taken, there may be a knock-on effect on workforce planning and the health of our future workforce. When medical students return to their universities, there is likely to be need for enhanced wellbeing support, adaptations in the short-term and long-term strategies for medical education, and provision of financial guidance.
Low-dose Whole-lung Irradiation for COVID-19 Pneumonia: Short Course Results
Authors: Ameri Ahmad , Rahnama Nazanin , Bozorgmehr Rama , Mokhtari Majid , Farahbakhsh Mohammad , Nabavi Mahmood , Shoaei Simin Dokht , Izadi Hossein , Kashi Amir Shahram Yousefi , Dehbaneh Hadiseh Shabanpour , Taghizadeh-Hesary Farzad 
Published: July 2020

Abstract
Objectives: The COVID-19 outbreak is affecting people worldwide. Most of the infected patients suffering from respiratory involvement that may progress to acute respiratory distress syndrome. This pilot study aimed to evaluate the clinical efficacy of low-dose whole-lung radiotherapy in patients with COVID-19 pneumonia. Methods: In this clinical trial, done in Iran, we enrolled patients with COVID-19 who were older than 60 years and hospitalized to receive supplementary oxygen for their documented pneumonia. Participants were treated with whole-lung irradiation in a single fraction of 0.5 Gy plus national protocol for the management of COVID-19. Vital signs (including blood oxygenation and body temperature) and laboratory findings (IL-6 and CRP) were recorded before and after irradiation.Results: Between 21 May 2020 and 24 June 2020, five patients received whole-lung irradiation. They followed for 5-7 days to evaluate response to treatment and toxicities. The clinical and paraclinical findings of four patients (except for patient #4 that get worst and died on day 3) improved on the first day of irradiation. Patient #3 opted-out the trial on the third day of irradiation. The mean time to discharge was 6 days for the other three patients. No acute radiation-induced toxicity was recorded.Conclusion: With a response rate of 80%, whole-lung irradiation in a single fraction of 0.5 Gy had encouraging results in oxygen-dependent patients with COVID-19 pneumonia.
PNPLA3 and TLL-1 polymorphisms affect disease severity in patients with COVID-19
Authors: Grimaudo Stefania , Amodio Emanuele , Pipitone Rosaria Maria , Maida Carmelo Massimo , Pizzo Stefano , Prestileo Tullio , Tramuto Fabio , Sardina Davide , Vitale Francesco , Casuccio Alessandra , Craxì Antonio 
Published: July 2020

Abstract
Introduction Albeit the pathogenesis of COVID-19 remains unclear, host’s genetic polymorphisms in genes infection and reinfection, inflammation, or immune stimulation could play a role in determining the course and outcome. Methods We studied in the early phase of pandemic consecutive patients (N=383) with SARS-CoV-2 infection, whose subsequent clinical course was classified as mild or severe, the latter being characterised by admission to intensive therapy unit or death. Five host gene polymorphisms (MERTK rs4374383, PNPLA3 rs738409, TLL-1 rs17047200, IFNL3 rs1297860, and INFL4 rs368234815) were assessed by using whole nucleic acids extracted from nasopharyngeal swabs. Specific protease cleavage sites of TLL-1 on the SARS-CoV-2 Spyke protein were predicted in silico. Results Male subjects and older patients were significantly at higher risk for a severe outcome (p=0.02 and p<0.001, respectively). By considering patients ≤ 65 years, after adjusting for potential confounding due to sex, an increased risk of severe outcome was found in subjects with the GG genotype of PNPLA3 (adj-OR: 4.69; 95% CI= 1.01-22.04) or TT genotype of TLL-1 (adj-OR=9.1; 95% CI= 1.45-57.3). In silico evaluation showed that TLL-1 is potentially involved in the Spike protein cleavage.Discussion Subjects carrying a GG genotype in PNPLA3 gene might have a constitutive upregulation of the NLRP3 inflammosome and be more prone to tissue damage when infected by SARS-CoV-2. The TT genotype in TLL-1 gene might affect its protease activity on the SARS-CoV-2 Spyke protein, enhancing the ability to infect or re-infect host’s cells. The untoward effect of these variants on disease course is evident in younger patients due to the relative absence of comorbidities as determinants of prognosis.
Effect of Various Barley Steeping Conditions on the Content of Albuminous Substances in the Malt
Authors: Rostovskaya Marina , Boyarova Margarita , Klykov Alexey 
Published: July 2020

Introduction. Malt production requires low-protein barley. Unfortunately, bad environmental conditions often lead to higher protein content than specified in the related standards. The research objective was to study the effect of barley steeping conditions on the level of albuminous substances in malt and to assess the possibility of reducing nitrogenous substances by changing the steeping regime.
Study objects and methods. The research featured two varieties of barely, namely “Primorsky 89” and “Primorsky 98”. Both varieties were harvested in 2013, 2015, and 2016 in the Primorye Region of Russia. The protein content in the grain of each variety differed significantly, depending on the year of harvest, and ranged from 1.75% to 2.5%. Two micromalting modes differed only in the steeping time and were performed at 17°C. The malt samples were analyzed for total protein content, total soluble nitrogen, Kolbach Index, and free amino nitrogen.
Results and discussion. The “Primorsky 89” variety proved insensitive to a longer steeping time, thus maintaining the same characteristics of the malt. The decrease in the protein level in the malt compared to the raw material was approximately the same for each mode and amounted to 0.3%. The Kolbach Index ranged between 30.31% and 35.1%. The experiment failed to produce the desired degree of dissolution, while the difference in this indicator under various modes was less than 1%. The long steeping mode proved optimal for the “Primorsky 98” variety. An increase in the steeping time made it possible to reduce the content of nitrogenous substances in the malt by 1%, compared to the raw material. Higher initial protein content in the grain resulted in lower content of nitrogenous substances during malting. The long steeping mode also resulted lowered the Kolbach Index by 3%: it was 34.7% – 39.5% for the long steeping mode and 31.1–36.8% for the short steeping mode.
Conclusion. The barley variety and the malting method affected the dynamics of nitrogenous substances. For some varieties, a longer steeping period proved to reduce the content of nitrogenous substances in the malt and increase the Kolbach Index.
Prospects for Digital and Innovative Technologies in Management Competitiveness of Enterprises
Authors: Mizanbekova Salima , Bogomolova Irina , Shatohina Nataliya 
Published: July 2020

Introduction. Enterprises of the grain industry make up an important part of the domestic agro-industrial complex. They are strategically important for food security and social stability. The present research featured the prospects for the use of innovative technologies by industry management in the conditions of economy digitalization and a chaotically changing market. The theory and practice of management has proved that the main component of improving the competitiveness of flour mills is the product quality.
Study objects and methods. The research objectives were to identify dynamics of the world and Russian grain market using statistical methods; to define the role of Russia in the world production and export of grain crops and flour; to assess the trends of the competitiveness of flour-milling enterprises in the Central black earth region of the Russian Federation; to identify problems and potential opportunities for improving the quality of grain and flour products; to analyze the business processes of leading enterprises in the region.
Results and discussion. The article introduces some recommendations on the use of digital technological solutions, modern software, and electronic mobile devices (probes) on grain harvesting and processing enterprises to ensure the safety and high standards of grain. The research confirmed that functional flour products can expand sales and strengthen the image of socially responsible companies. The list of raw technological innovations included fortification, mixing, and flour dying. The authors calculated the profits of management innovations, e.g. flour quality assessment in outsourcing laboratories.
Conclusion. The results can help flour milling enterprises to expand the profile of their activities and increase the competitiveness