bluuebunny/crossref_metadata_2025 huggingface dataset:
Gastric Cancer Surgical Experience from a single expert Western center: case series results
Authors: graziosi Luigina , marino elisabetta , Avenia Stefano , Vannoni Maria Cristina , Donini Annibale
Published: October 2020

Background Surgical treatment plays a key role in the cure of gastric cancer. Our aim was to analyze changes in epidemiology and outcome, over a time period of 15 years.Methods 410 patients operated between January 2004 and December 2018 were enrolled. Patients were subdivided into 3 groups. The entire cohort was evaluated, and a more detailed analysys was made in patients that underwent a curative surgery. Survival outcomes and oncological surgical outcomes have been described and correlated with Overall Survival.Results Results showed an increase trend in gastric cancer operation over the time period analyzed (p< 0.05). Overall and disease free survival did not vary in the different time periods. In patients treated with the intent to cure: 5- and 10-Year survivals were respectively: 44% and 34.7%; 5- and 10 years disease free survival were 50.7 and 49.4%. Type of lymphadenectomy and number of lymphondal harvested changed significantly over the time (p < 0.05). Conclusions Our result showed an increasing trend in number of surgery for gastric adenocarcinoma in our center, probably due to the increasing in absolute number of cases in Italy and worldwide. We have also show that tumor location is shifting towards a distal location in the last period. Moreover in the last period there is also an improving trend in overall survival, probably due to a more aggressive surgery adopted and also due to an improved learning curve. Gastric surgery must be done in an experienced center to obtain oncological outcomes; in selected cases an extended lymphadenectomy could give survival benefit to patients with locally advanced gastric cancer.
The biometric parameters of aniso-astigmatism and its risk factor in Chinese preschool children: the Nanjing Eye Study
Authors: Tong Haohai , Hao Qingfeng , Wang Zijin , Wang Yue , Li Rui , Zhao Xiaoyan , Sun Qigang , Zhang Xiaohan , Chen Xuejuan , Zhu Hui , Huang Dan , Liu Hu
Published: October 2020

Backgrounds: Aniso-astigmatism may hinder normal visual development in preschool children. Knowing its prevalence, biometric parameters and risk factors is fundamental to children eye care. The purpose of this study was to determine the biometric components of aniso-astigmatism and associated maternal risk factors in Chinese preschool children.Methods: In the population-based, prospective cohort Nanjing Eye Study, children were measured for noncycloplegic refractive error using an autorefractor and for biometric parameters using an optical low-coherent reflectometry. The difference of total astigmatism (TA) between both eyes was calculated using cylinder power (non-vectorial aniso-TA was defined as ≥1.00 Dioptre Cylinder [DC] between both eyes) and by vector analysis (vectorial aniso-TA was defined as a difference of ≥0.5 in J0 or J45 between both eyes which is equivalent to 1.00 DC). The prevalence of aniso-TA was presented. Interocular biometric parameters were compared between with vs. without aniso-astigmatism group. In addition, risk factors were determined using multivariate logistic regression model.Results: Of 1131 children (66.90±3.38 months, 53.31% male), the prevalence of non-vectorial aniso-TA was 1.95% (95% Confidence Interval (CI)=1.14%-2.75%), while the prevalence of vectorial aniso-TA was twice as common as non-vectorial aniso-TA, neither varying with sex or age. With aniso-TA eyes were more asymmetric in axial length and corneal curvature radius than without aniso-TA eyes. In multivariate logistic regression model, 5-min Apgar score less than 7 was significantly associated with higher risk of aniso-TA (vectorial aniso-TA: Odds Ratio (OR)=6.42, 95%CI=2.63-15.69, P<0.001; non-vectorial aniso-TA: OR=4.99, 95%CI=1.41-17.68, P=0.01）. Being twin or triple was significantly associated with higher risk of vectorial aniso-CA (OR=2.43, 95%CI=1.05-5.60, P=0.04). Pre-term delivery (OR=2.60, 95%CI=1.09-6.15, P=0.03) and post-term delivery (OR=3.61, 95%CI=1.31-9.96, P=0.01) were significantly associated with higher risk of vectorial aniso-CA.Conclusions: Both corneal curvature radius and axial length asymmetry were correlated with aniso-TA. Children with 5-min Apgar score<7 were more likely to have aniso-TA, while twin or triple, pre-term or post-term delivery were more likely to have vectorial aniso-CA.
Evaluating a web- and telephone-based personalised exercise intervention for individuals living with metastatic prostate cancer (ExerciseGuide): protocol for a pilot randomised controlled trial
Authors: Evans Holly EL , Forbes Cynthia C , Galvão Daniel A , Vandelanotte Corneel , Newton Robert U , Wittert Gary , Chambers Suzanne , Vincent Andrew D , Kichenadasse Ganessan , Brook Nicholas , Girard Danielle , Short Camille E
Published: October 2020

Introduction:Preliminary research has shown the effectiveness of supervised exercise-based interventions in alleviating sequela resulting from metastatic prostate cancer. Despite this, many individuals do not engage in sufficient exercise to gain the benefits. There are many barriers which limit the uptake of face-to-face exercise in this population including lack of suitable facilities, remoteness, access to experts, significant fatigue, urinary incontinence, and motivation. Technology-enabled interventions offer a distance-based alternative. This protocol describes a pilot two-armed randomised controlled study that will investigate the feasibility and preliminary efficacy of an online exercise and behavioural change tool (ExerciseGuide) among individuals with metastatic prostate cancer.Methods:Sixty-six participants with histologically diagnosed metastatic prostate cancer will be randomised into either the eight-week intervention or a wait-list control. The intervention arm will have access to a tailored website, remote supervision, and three tele-coaching sessions to enhance support and adherence. Algorithms will individually prescribe resistance and aerobic exercise based upon factors such as metastasis location, pain, fatigue, confidence, and current exercise levels. Behavioural change strategies and education on exercise benefits, safety and lifestyle are also tailored through the website. The primary outcome will be intervention feasibility (safety, usability, acceptability, adherence). Secondary exploratory outcomes include changes in physical activity, quality of life, sleep, and physical function. Outcomes will be measured at baseline and week 9.Discussion:The study aims to determine the potential feasibility of an online remotely-monitored exercise intervention developed for individuals with metastatic prostate cancer. If feasible, this pilot intervention will inform the design and implementation of further distance-based interventions.Trial registration: ANZCTR, ACTRN12614001268639. Registered 10th December 2018, https://anzctr.org.au/ACTRN12618001979246.aspxProtocol issue: Version 1 (9th March 2020).
Long noncoding RNA UPK1A-AS1 indicates poor prognosis of hepatocellular carcinoma and promotes cell proliferation through interaction with EZH2
Authors: Zhang Dong-Yan , Sun Qing-Can , Zou Xue-Jing , Song Yang , Li Wen-Wen , Guo Ze-Qin , Liu Shan-Shan , Liu Li , Wu De-Hua
Published: October 2020

Background: Dysregulation of long non-coding RNAs (lncRNAs) is responsible for cancer initiation and development, positioning lncRNAs as not only biomarkers but also promising therapeutic targets for cancer treatment. A growing number of lncRNAs have been reported in hepatocellular carcinoma (HCC), but their functional and mechanistic roles remain unclear. Methods: Gene Set Enrichment Analysis was used to investigate the molecular mechanism of UPK1A antisense RNA 1 (UPK1A-AS1). Cell Counting Kit-8 assays, EdU assays, flow cytometry, western blotting, and xenograft assays were used to confirm the role of UPK1A-AS1 in the proliferation of HCC cells in vitro and in vivo . Bioinformatics analyses and quantitative polymerase chain reaction (qRT-PCR) were performed to explore the interplay between UPK1A-AS1 and enhancer of zeste homologue 2 (EZH2). RNA immunoprecipitation (RIP), RNA pull-down assays, western blotting, and qRT-PCR were conducted to confirm the interaction between UPK1A-AS1 and EZH2. The interaction between UPK1A-AS1 and miR-138-5p was examined by luciferase reporter and RIP assays. Finally, the expression level and prognosis value of UPK1A-AS1 in HCC were analyzed using RNA sequencing data from The Cancer Genome Atlas datasets. Results: We showed that UPK1A-AS1, a newly identified lncRNA, promoted cellular proliferation and tumor growth by accelerating cell cycle progression. Cell cycle-related genes, including CCND1, CDK2, CDK4, CCNB1, and CCNB2, were significantly upregulated in HCC cells overexpressing UPK1A-AS1. Furthermore, overexpression of UPK1A-AS1 could protect HCC cells from cis-platinum toxicity. Mechanistically, UPK1A-AS1 interacted with EZH2 to mediate its nuclear translocation and reinforce its binding to SUZ12, leading to increased H27K3 trimethylation. Targeting EZH2 with specific small interfering RNA impaired the UPK1A-AS1-mediated upregulation of proliferation and cell cycle progression-related genes. Moreover, miR-138-5p was identified as a direct target of UPK1A-AS1. Additionally, UPK1A-AS1 was significantly upregulated in HCC, and the upregulation of UPK1A-AS1 predicted poor prognosis for patients with HCC. Conclusions: Our study revealed that UPK1A-AS1 promotes HCC development by accelerating cell cycle progression through interaction with EZH2 and sponging of miR-138-5p, suggesting that UPK1A-AS1 possesses substantial potential as a novel biomarker for HCC prognosis and therapy.
Isolation and identification of a novel bacterium, Pseudomonas sp. ZyL-01, involved in the biodegradation of CL-20
Authors: Liu Zhiyong , Dang Kai , Li Cunzhi , Gao Junhong , Wang Hong , Gao Yongchao , Zhao Bin , Fan Peng , Qian Airong
Published: October 2020

Hexanitrohexaazaisowurtzitane (CL-20) is a compound with a polycyclic cage and an N-nitro group that has been shown to play an unfavorable role in environmental fate, biosafety, and physical health. The aim of this study was to isolate the microbial community and to identify a single microbial strain that can degrade CL-20 with desirable efficiency. Metagenomic sequencing methods were performed to investigate the dynamic changes in the composition of the community diversity. The most varied genus among the microbial community was Pseudomonas, which increased from 1.46% to 44.63% during the period of incubation (MC0–MC4). Furthermore, the new strain was isolated and identified from the activated sludge by bacterial morphological and 16s rRNA sequencing analyses. The CL-20 concentrations decreased by 75.21 μg/mL and 74.02 μg/mL in 48 h by MC4 and Pseudomonas sp. ZyL-01, respectively. Moreover, ZyL-01 could decompose 98% CL-20 of the real effluent in 14 day’s incubation with the glucose as carbon source. Finally, a draft genome sequence was obtained to predict possible degrading enzymes involved in the biodegradation of CL-20. Specifically, 330 genes that are involved in energy production and conversion were annotated by Gene Ontology functional enrichment analysis, and some of these candidates may encode enzymes that are responsible for CL-20 degradation. In summary, our studies indicate that microbes might be a valuable biological resource for the treatment of environmental contamination caused by CL-20 and that Pseudomonas sp. ZyL-01 might be a promising candidate for eradicating CL-20 to achieve a more biosafe environment and improve public health.
The association between frequency of eating out with overweight and obesity among children aged 6-17 in China: A National Cross-sectional Study
Authors: ma Yanning , Gong Weiyan , Ding Caicui , Song Chao , Yuan Fan , Fan Jing , Feng Ganyu , Chen Zheng , Liu Ailing
Published: October 2020

Background: In parallel with the increased prevalence of childhood overweight and obesity, the rate of eating out in China has increased dramatically in recent years. The purpose of the study was to explore the association between frequency of eating out with overweight and obesity among Chinese children.Methods: The representative sample of Chinese children aged 6-17 years (7685 boys; 7576 girls) was recruited from Chinese National Nutrition and Health Survey (CNNHS) in 2010-2012. Frequency of eating out was collected by interview-administered questionnaire and categorized as: less than once per week, once and twice per week, and three times or more per week. Height and weight were measured (body mass index was consequently calculated). Results：The prevalence of eating out among Chinese children aged 6-17 years old was 23.2%. Children who ate out 0, 1-2, ≥3 times per week were accounted for 76.8%, 10.9% and 12.3% respectively. Findings revealed that eating out three times per week or more was statistically significant associated with higher prevalence of overweight and obesity among boys (OR=1.20,95CI:1.04-1.38) compared with those ate out less than three times per week. However, no significantly association was observed among girls (OR=0.91, 95CI:0.78-1.01). In additional, Younger children, rural children, children from low income family, those with leisure exercises (certain physical activities regularly carried out such as swimming, walking, running, equipment fitness), leisure time sedentary behaviors (LTSB)(>2h/d) were relatively more likely to eat out. Conclusions: The results illustrated that eating out three times or more had a significantly positive effect on overweight and obesity among boys in China.
Suspected Heparin-Induced Thrombocytopenia in a COVID-19 Patient on Extracorporeal Membrane Oxygenation Support: A Case Report.
Authors: Phan Xuan T. , Nguyen Tuan Huu , Tran Tung T. , Huynh Thu-Hien T. , Hoang Thuy-Ha T. , Nguyen Vinh-Chau V. , Pham Thao N. T.
Published: October 2020

Background: Extracorporeal membrane oxygenation (ECMO) support can be life-saving in critically ill COVID-19 patients. However, there are many complications associated with this procedure, including Heparin-induced thrombocytopenia (HIT.) Despite its rarity in ECMO cases, HIT can lead to devastating consequences and is difficult to manage. Case presentation: In this report, we present a case of a COVID-19 patient on ECMO support who was diagnosed with HIT and required intensive treatment. Initially, HIT was only suspected due to newly-developed thrombocytopenia and oxygenator dysfunction, with thrombi observed later. Regarding his treatment, since there was no recommended replacement to heparin available to us at the time of diagnosis, we decided to use rivaroxaban temporarily. No adverse events were recorded during that period. The patient was able to make a full recovery.Conclusion: HIT may jeopardize patient’s care during ECMO. As COVID-19 may bring about a surge in the number of patients requiring ECMO support, we need consented guidance to optimize treatment in this specific situation.
Evaluation Of The Pediatric Life Support Instructors Courses 
Authors: Lopez-Herce Jesus , Carrillo Angel , Urbano Javier , Manrique Gema , Mencía Santiago , Pediátricos Grupo Madrileño Cuidados Intensivos
Published: October 2020

Objective To evaluate the results and quality of pediatric cardiopulmonary resuscitation (CPR) instructor training courses. Methods A retrospective analysis was performed of the results of 24 pediatric CPR instructor courses held over 21 years (1999 to 2019). The results of participants’ evaluation of theory and practice sessions were analyzed. In addition, participants were asked to answer an anonymous survey to assess their opinion on the quality of theory and practice lessons, course organization and methodology, and instructor training. The results were compared by professional groups. Results A total of 560 participants completed the instructor course. Of them, 554 passed theory and practice tests (98.9%). The mean score obtained in theory tests was 9.2 (0.8) out of 10. The mean score obtained in all practice tests was > 3.5 out of 5. Participants evaluated all the aspects of the course (theory and practice content, organization, teaching methodology, and instructors) with mean scores over 8 out of 10.Conclusions Specific pediatric and neonatal CPR instructor courses are a cornerstone in the process of CPR training and ensuring the homogeneity and quality of training. Most of the participants obtained the qualification of instructors and their evaluation of the course was very positive.
Inspiratory plus expiratory neuromuscular electrical stimulation versus diaphragm pacing for rehabilitation in severe COPD patients: a randomized controlled trial
Authors: Zhao Zhiling , Wang Xiaojuan , Sun Wuzhuang , Zhao Xiaoyun , Lin Yingxiang , Zhang Shu , Li Zhu , Lu Yong , Wang Wen , Gong Juanni , Liu Yan , Yu Yanxia , Li Bojun , Hu Xiujuan , Li Yuechuan , Tong Zhaohui
Published: October 2020

Background: Chronic obstructive pulmonary disease (COPD) is a progressive lung disease, which might be improved by neuromuscular electrical stimulation. To date, no trials of intervention of inspiratory plus expiratory neuromuscular electrical stimulation have been conducted. This study aimed to evaluate the effect and safety of in patients with severe COPD.Methods: In this prospective, multicenter controlled trial, 120 stable patients with severe COPD who received standard medical treatment were randomized assigned 1:1 to receive either inspiratory plus expiratory neuromuscular electrical stimulation (study intervention) or stimulation of the phrenic nerve, called diaphragm pacing (control intervention). Intention-to-treat analysis was carried out. The primary outcome was to analyze the changes in functional exercise capacity, estimated as six-minute walk distance (6MWD), following four weeks of electrical stimulation intervention.Results: The change in 6MWD was greater in the study intervention (65.53 ± 39.45m) than in the control intervention (26.66 ± 32.65m). The mean between-group difference at four weeks was 29.07 m ([95% CI, 16.098 to 42.035]; P < 0.001). There was no significant between-group difference in secondary (modified Medical Research Council, forced expiratory volume in 1 second (FEV1), FEV1% predicted, and FEV1 ratio forced vital capacity (FEV1/FVC)) outcomes after four weeks of electrical stimulation. For GOLD 4 subjects, FEV1 and FEV1/FVC had improved in the study intervention (P < 0.05). No electrical stimulation-related serious adverse events were observed in either group.Conclusion: Functional exercise capacity were significantly improved in the study intervention in stable patients with severe COPD after four weeks of treatment.Trial registration: ChiCTR, ChiCTR2000032681. Registered 6 May 2020- Retrospectively registered,http://www.chictr.org.cn/showproj.aspx?proj=53086.
Associations between animal and herd management factors, serological response to three respiratory pathogens and pluck lesions in finisher pigs on a farrow-to-finish farm
Authors: Fitzgerald Rose Mary , O'Shea Helen , Manzanilla Edgar García , Moriarty John , McGlynn Hugh , Díaz Julia Adriana Calderón
Published: October 2020

Background: Serological screening is a common method to monitor antibody response to pathogen exposure, but results could vary due to several factors. This study aimed to quantify animal and management related factors associated with variation in antibody levels in finisher pigs at slaughter, in an Irish farrow-to-finish farm endemically infected with Actinobacillus pleuropneumonia (App), Mycoplasma hyopneumoniae (Mhyo) and swine influenza virus (SIV). A second objective was to estimate differences in antibody levels in pigs presenting pluck lesions. This was an observational study whereby pigs were managed as per routine farm practice. Data on sow parity, number of born alive (NBA) pigs per litter, cross-fostering status, birth and weaning body weight were recorded from 1,016 pigs born from one farrowing batch. At slaughter, blood samples were collected for serological analysis and pigs were inspected for presence of enzootic pneumonia (EP)-like lesions, pleurisy, pericarditis and heart condemnations. Pigs were retrospectively classified into three production flows, depending on time spent in each production stage: flow 1 (F1; pigs followed the normal production flow); flow 2 (F2; pigs which were delayed by 1 week from advancing forward); and flow 3 (F3; pigs delayed by >1 week from advancing forward). A nested case-control design was applied by matching pigs from each flow by sow parity, birth weight and NBA.Results: Pigs born from primiparous sows had higher antibody levels for App than those born to parity ≥5 sows (P<0.05) and there was no association between any of the pathogens investigated and other early life indicators (P>0.05). Pigs in F1 had lower antibody levels for App but higher antibody levels for SIV than F2 and F3 pigs (P<0.05). There was no association between pluck lesions and respiratory pathogens (P>0.05), except for increased antibody levels for Mhyo when EP-like lesions were present (P=0.006). Conclusion: Results indicate that offspring from primiparous sows develop higher antibody levels for App IV toxin when exposed to this disease and that enforcement of a strict all-in/all-out production system would reduce on-farm disease circulation. A high percentage of pigs were affected with EP-like lesions which were associated with higher antibody levels for Mhyo.
An Internet-Based Self-Help Intervention for People with Psychological Distress Due to COVID-19: Study Protocol for A Randomized Controlled Trial.
Authors: Brog Noemi Anja , Hegy Julia , Berger Thomas , Znoj Hansjörg
Published: October 2020

Background: The Coronavirus-19 (COVID-19) has reached pandemic status and is affecting countries all over the world. The COVID-19 pandemic is accompanied by various stressors that require adjustment in everyday life and possibly changes in personal future prospects. While some individuals cope well with these challenges, some develop psychological distress including depressive symptoms, anxiety or stress. Internet-based self-help interventions have proven to be effective in the treatment of various mental disorders such as depression and anxiety. Based on that, we developed an internet-based self-help program for individuals with psychological distress due to the situation surrounding the COVID-19 pandemic. The 3-week self-help program consists of 6 modules comprising texts, videos, figures and exercises. Participants can request guidance within the self-help program (guidance on demand). The primary aim of this study is to evaluate the efficacy and feasibility of the self-help program compared to a waiting control condition.Methods: The design is a randomized controlled trial. Participants are allocated to a 3-week self-help intervention plus care as usual or a 3-week waiting period with only care as usual. There are follow-ups after 6 weeks and 18 weeks. At least 80 participants with COVID-19 pandemic related psychological distress will be recruited. Primary outcome are depressive symptoms. Secondary outcomes include anxiety and chronic stress, suicidal experiences and behaviour, health-related quality of life, generalized optimism and pessimism, embitterment, optimistic self-beliefs, emotion regulation skills, loneliness, resilience and the satisfaction with and usability of the self-help program.Discussion: To the best of our knowledge, this is one of the first studies investigating an internet-based self-help program for psychological distress due to the situation surrounding the COVID-19 pandemic. Thus, the results of this study may give further insight into the use of internet-based self-help programs in pandemic-related psychological distress.Trial registration: ClinicalTrials.gov, NCT04380909, Retrospectively registered on 8 May 2020, https://clinicaltrials.gov/ct2/show/NCT04380909
Evaluation of Cardiovascular Risk Factors in Patients With Familial Hypercholesterolemia From the North-Eastern Area of Romania
Authors: Vlad Cristiana-Elena , Foia Liliana , Florea Laura , Costache Irina-Iuliana , Covic Andreea , Popescu Roxana , Reurean-Pintilei Delia , Covic Adrian
Published: October 2020

Background. Familial hypercholesterolemia (FH) is one of the most frequent and important monogenic cholesterol pathologies. Traditional and nontraditional cardiovascular risk factors increase the prevalence of atherosclerotic cardiovascular disease (ASCVD) in this population. Objective. (a)To identify FH patients in the North-Eastern part of Romania and to analyze demographic, clinical and paraclinical data (b)to identify of new cardiovascular events in FH patients throughout the follow-up based on the administrated lipid lowering drugs.Methods. This first prospective study in the North-Eastern part of Romania was carried out between October 2017 and October 2019; out of 980 patients with dyslipidemia evaluated with the Dutch Lipid Network (DLCN) and Simon Broome (SM) scores, only 61 patients with DLCN score above 3 and possible/probable FH (SM score) were included.Results. The 61 FH subjects recorded a mean age of 48.5±12.5 years, with more female patients than male patients. Hypertension was the main cardiovascular risk factor for both sexes, followed by physical inactivity and obesity for the female FH group and active smoker for the male FH group. The measured DLCN score recorded: “possible” FH identified in 39.4%, “probable” FH in 45.9% and “definite” FH in 14.7%. After the administration of the lipid-lowering agents for 24 months, low-density cholesterol lipoprotein(LDL-C) levels and carotid intima-media thickness(cIMT) have decreased, while the ankle-brachial index(ABI) and high-density cholesterol lipoprotein(HDL-C) levels have increased. Also, the cIMT values over 0.9mm, total cholesterol(TC), triglyceride(TG), and high-sensitivity C-reactive protein(hsCRP) levels were associated with an increased risk of ASCVD. In addition, statins administrated in monotherapy have delayed de new cardiovascular events.Conclusions. To obtain a reduction of cardiovascular events, FH patients need cascade screening for early identification and a specific management with possible administration of monoclonal antibodies, despite the significant socio-economic barriers.
Mesenchymal Stem Cells and Acelluar Products Attenuate Murine Induced Colitis
Authors: Li Yan , Altemus Jessica , Lightner Amy L.
Published: October 2020

Background: Mesenchymal stem cells (MSCs) are a well-established immunomodulatory agent which can also promote tissue repair and regeneration. Recent studies have demonstrated MSCs as a novel therapeutic for inflammatory bowel disease (IBD), a chronic idiopathic inflammatory disorder of the gastrointestinal tract. However, the precise role of MSCs in regulating immune responses is controversial, and its significance in the pathogenesis remains IBD undefined. In addition, MSCs’ acellular product, extracellular vesicles (EVs), may also play an important role in the armamentarium of therapeutics, but how EVs compare to MSCs remains unknown due to the lack of side-by-side comparative investigation. We herein compared MSCs and MSC-derived EVs for the treatment of IBD using a DSS-induced colitis model. Methods: A DSS-induced colitis model was used. At Day 4, mice received adipose derived MSCs, MSC-derived EVs, or placebo. Weight loss, stool consistency and hematochezia was charted. At day 8, murine colons were harvested, histologic analysis performed, and serum/tissue cytokine analysis conducted. Results: MSCs and EVs demonstrated equivalent immunosuppressive function in DSS-treated mice through decreased colonic lymphocyte infiltration and attenuated disease severity after both MSC and EV treatment. Importantly, the ability to inhibit inflammation in the DSS colitis model was equivalent for both MSCs and MSC-derived EVs. Conclusions: These results suggest that (i) both MSCs and EVs are effective therapeutic candidates for a DSS-induced mouse colitis model, (ii) MSCs and EVs have similar immunosuppressive and anti-inflammatory functions, and (iii) EVs may present a novel future therapeutic for the treatment of IBD.
CBX3 regulated by miR-139 promoted the development of HCC by regulating cell cycle progression
Authors: Zhang Pan , Yang Xiaoyan , Zha Zhongming , Zhu Yumeng , Zhang Guoqiang , Li Guotao
Published: October 2020

Background

Hepatocellular carcinoma (HCC), comprises of the major primary liver cancer, is one of the most lethal malignancies in the world [1]. Increasing evidence has demonstrated that chromobox protein homolog 3 (CBX3) functioned as an oncogene in different cancers. However, its expression profiles and biological functions in HCC remain exactly unknown.
Methods

Data of CBX3 expression in HCC acquired from TCGA and GEO databases were analyzed. The biological functions of CBX3 in HCC were examined by in vitro experiments. Bioinformatics analysis, qRT-PCR and western blot were performed to explpore the mechanism of CBX3 involved in HCC.
Results

CBX3 mRNA was upregulated in HCC tissues, and overexpression of CBX3 mRNA was negatively correlated with malignancies and poor prognosis in HCC patients. Knocking down of CBX3 induced slower growth, less migration and fewer invasions of the HCC cells in vitro. Moreover, bioinformatics analysis and experimental observation indicated that CBX3 expression was correlated with cell cycle regulation proteins of HCC cells. Finally, Starbase predicted that the miR-139 could directly target CBX3 in HCC; Confirmatory experiments verified that miR-139 overexpression attenuated the HCC cells proliferation and migration, which could be reversed by overexpressing CBX3 concurrently.
Conclusion

Our results concluded that miR-139/CBX3 axis may involve in the HCC development through regulating cell cycle progression and may be a promising target in the treatment of HCC.
Missing clinical trial data: the evidence gap in the safety of potential COVID-19 drugs
Authors: Rodgers Florence , Pepperrell Toby , Keestra Sarai , Pilkington Victoria
Published: October 2020

Background: Several drugs are being repurposed for the treatment of the coronavirus disease 2019 (COVID-19) pandemic based on in vitro or early clinical findings. As these drugs are being used in varied regimens and dosages, it is important to enable synthesis of existing safety data from clinical trials. However, availability of safety information is limited by a lack of timely reporting of clinical trial results on public registries or through academic publication. We aimed to analyse the evidence gap in safety data by quantifying the number of missing clinical trial results for drugs potentially being repurposed for COVID-19 by conducting a rapid review of results posting on ClinicalTrials.gov and in academic publications.

Methods: ClinicalTrials.gov was searched for 19 drugs that have been identified as potential treatments for COVID-19. Relevant clinical trials for any prior indication were listed by identifier (NCT number) and checked for results and for timely result reporting (within 395 days of the primary completion date). Additionally, PubMed and Google Scholar were searched to identify publications of results not listed on the registry. A second, blinded search of 10% of trials was conducted to assess reviewer concordance.

Results: Of 3754 completed trials, 1516 (40.4%) did not post results on ClinicalTrials.gov or in the academic literature. 1172 (31.2%) completed trials had tabular results on ClinicalTrials.gov. A further 1066 (28.4%) completed trials had results from the literature search, but did not report results on ClinicalTrials.gov. Key drugs missing clinical trial results include hydroxychloroquine (37.0% completed trials unreported), favipiravir (77.8%) and lopinavir (40.5%).

Conclusions: There is an important evidence gap for the safety of drugs being repurposed for COVID-19. This uncertainty could cause a large burden of additional morbidity and mortality during the pandemic. We recommend caution in experimental drug use for non-severe disease and urge clinical trial sponsors to report missing results retrospectively.
Quasi-biennial oscillation disrupted by abnormal Southern Hemisphere stratosphere
Authors: Anstey James , Banyard Tim , Butchart Neal , Coy Lawrence , Newman Paul , Osprey Scott , Wright Corwin
Published: October 2020

The quasi-biennial oscillation (QBO) is a repeating cycle of tropical stratosphere winds reversing direction from eastward to westward roughly every 14 months. Discovered independently by British and American scientists the QBO continued uninterrupted for 27 cycles from 1953 until February 2016 when a westward jet unexpectedly formed in the lower stratosphere during the eastward phase. This disruption is attributed to unusually high wave-momentum fluxes from the Northern Hemisphere. A second, similar, QBO disruption occurred during the 2019/2020 northern winter though wave fluxes from the Northern Hemisphere were weak. Here we show that this latest disruption to the regular QBO cycling was stronger than that seen in 2016 and resulted from horizontal momentum transport from the Southern Hemisphere during abnormal winter conditions. In both disruptions the normal downward progression of the QBO halts and the eastward shear zone above the disruption moves upward assisted by stronger tropical upwelling during the boreal winter. The predictable signal associated with the QBO's quasi-regular phase progression is permanently lost during disruptions and the oscillation reemerges after a few months significantly shifted in phase from what would be expected if the phase had progressed uninterrupted. We infer from an increased wave-momentum flux into equatorial latitudes seen in model climate projections supporting the latest Intergovernmental Panel on Climate Change (IPCC) assessment that disruptions to the QBO are likely to be more common in future. Consequently, we anticipate that in future the QBO will be a less reliable source of predictability on lead times extending out to several years than it currently is.
Behavioral appraisal by implementing a short sequence of stress resolves adaptively changed stress gains
Authors: Lee Eun-Hwa , Park Jin-Young , Kwon Hye-jin , Han Pyung-Lim
Published: October 2020

Chronic stress produces adaptive changes in the brain via the cumulative action of glucocorticoids, which causes psychiatric illnesses such as depression. Here we show that a behavioral method implementing weak stress does not strengthen but resolves existing stress gains. Chronic stress produces persistent depressive behaviors in mice, and repeated daily treatment with 5-min restraint produces antidepressive effects. Repeated treatment with low-dose glucocorticoids mimics the anti-depressive effects of weak stress. Repeated weak stress or low-dose glucocorticoid treatment distinctively activates the prelimbic cortex (PL), and reverses the stress-induced altered gene expression profiles. Chemogenetic inhibition of PL outputs projecting to the nucleus accumbens, basolateral amygdala, or bed nucleus of the stria terminalis (BNST) dissipates antidepressive effects of weak stress, but only the PL-to-BNST circuit produces changes in dysregulated glucocorticoid release. Our results suggest that behavioral appraisal by implementing weak stress can resolve adaptively altered stress gains and rectify stress-induced depressive behaviors.
An Empirical Model to Estimate the Effect of Social Distance Levels on COVID-19 Outbreak
Authors: Tabesh Hamed , Saki Azadeh , Saki Rozita
Published: October 2020

The implementation of social distancing measures for controlling the outbreak of coronavirus disease 2019 (COVID‑19) in different countries has not been at the same level due to differences in policies, economies, and cultures. Hence, the effect of this pandemic on different aspects of societies varies depending on several factors.In this study, we found that the speed of disease transmission is directly related to the odds of being exposed to the disease in the society, that is directly related to the level of practicing social distancing measures. We introduced the weekly growth ratio (WGR) index and proposed an experimental rule model to monitor the current level of social distancing and predict the levels of intervention so as to reduce the WGR and control the sequential peaks. Our model showed that the minimum level of practicing social distancing in the community should be 80% to control the first peak of the disease; but after controlling the first peak, maintaining 50% of social distancing policies continuously keeps the number of cases/deaths constant and prevents the occurrence of a new peak.
Tartrate-resistant acid phosphatase 5 serves as a viable target against pulmonary fibrosis by modulating β-catenin signaling
Authors: Hu Yinan , Yu Jun , Wang Qi , Zhou Qing , Deng Yanhan , Liu Juan , Zhang Lei , Xu Yongjian , Xiong Weining , Wang Yi
Published: October 2020

Idiopathic pulmonary fibrosis (IPF) is a fatal interstitial lung disease with limited therapeutic options. Tartrate-resistant acid phosphatase 5 (ACP5) performs a variety of functions. However, its role in IPF remains unclear. Here, we demonstrated that the levels of ACP5 were increased in IPF patient samples and mice with bleomycin (BLM)-induced pulmonary fibrosis. In particular, higher levels of ACP5 were noted in the sera of IPF patients with a diffusing capacity of the lungs for carbon monoxide (DLCO) less than 40% of the predicted value. Additionally, Acp5 deficiency protected mice from BLM-induced lung injury and fibrosis and reduced the differentiation and proliferation of fibroblasts. Mechanistic studies revealed that Acp5 was upregulated by TGF-β1 in a TGFβR1/Smad3-dependent manner, after which Acp5 dephosphorylated p-β-catenin at Ser33 and Thr41, inhibiting the degradation of β-catenin and subsequently enhancing β-catenin signaling in the nucleus, which promoted the differentiation and proliferation of fibroblast. Notably, the treatment of mice with BLM-induced fibrosis with Acp5 siRNA-loaded liposomes robustly reversed lung fibrosis. Collectively, these data indicate that Acp5 plays an essential role in the initiation and progression of pulmonary fibrosis; therefore, strategies aimed at silencing Acp5 could be novel therapeutic approaches against pulmonary fibrosis in a clinical setting.
Gold(I)-Catalyzed Intramolecular Cyclization/Intermolecular Cycloaddition Cascade: Fast Track to Polycarbocycles and Mechanistic Insights
Authors: Zhang Cheng , Hong Kemiao , Pei Chao , Zhou Su , Hu Wenhao , Hashmi A. Stephen K. , Xu Xinfang
Published: October 2020

Herein we report a gold-catalyzed cascade protocol for the assembly of polycarbocyclic frameworks in high yields under mild reaction conditions. Mechanistic studies indicate that the unique β-aryl gold-carbene species, generated via gold-promoted 6-endo-dig diazo-yne cyclization, is the key intermediate in this reaction, followed by a [4 + 2]-cycloaddition with external alkenes. In comparison to the well-documented metal carbene cycloadditions, this is the first example of the carbene intermediate to serve as a 4-C synthon in a cycloaddition reaction. A variety of elusive π-conjugated polycyclic hydrocarbons (CPHs) with multiple substituents are readily accessible from the initially generated products by a mild oxidation procedure.
The Novel Biomarkers-Based HALP (Hemoglobin, Albumin, Lymphocyte And Platelet)-Prognostic Model For Acute And Subacute Patients With Cerebral Venous Sinus Thrombosis: A Retrospective Cohort Study
Authors: Li Shen , Liu Kai , Gao Yuan , Zhao Lu , Fang Hui , Zhang Rui , Liu Hongbing , Zhao Jiawei , Xia Zongping , Xu Yuming , Song Bo
Published: October 2020

Background: To evaluate the prognosis values of HALP in acute or subacute cerebral venous sinus thrombosis (CVST), to explore the new prognostic model for CVST.Methods: Consecutive patients who were diagnosed as having acute and subacute CVST were retrospectively investigated. We determined the patients' functional outcomes by modified Rankin Scale (mRS). Multivariate logistic regression analysis was used to assess the relationship between factors and poor functional outcomes. The area under the ROC curve (AUC) was estimated to evaluate the ability of markers and models in predicting clinical prognosis. The prognostic model was presented as nomogram. In addition, the decision curve analysis (DCA) was used to analyze the benefit of this model. Furthermore, survival curves were described by the Kaplan‑Meier analysis. Results: A total of 270 patients were included of which 31 had poor outcome. Multivariable logistic regression analysis demonstrated HALP (OR=0.978, 95%CI: 0.958-0.999, P=0.039) was a protective predictor of outcome. The AUC of HALP was 0.749 (95% CI: 0.633-0.865, P=0.044). DCA demonstrated that this model significantly improved risk prediction at threshold probabilities of CVST at 0 to 85%. Patients with higher HALP (P=0.006) presented higher overall survival rates. Conclusions: HALP may be a potential protective marker in acute and subacute CVST patients. The new prognostic model with HALP had potentially better value for Chinese CVST patients.
A Novel Culturing Chip (cChip) Can Facilitate Culturing of Unculturable Bacteria From Aquatic Environment
Authors: Lodhi Adil Farooq , Zhang Ying , Adil Maria , Deng Yulin
Published: October 2020

Background: Culturing the unculturable microorganisms is an important aspect of microbiology. Once cultured the unculturable microorganisms can be a source of useful antibiotics, enzymes etc. Several studies have been conducted on culturing the unculturable microorganisms from soil. But little knowledge exists about culturing such bacteria from aquatic environment. Therefore, in this study we designed a novel culturing chip (cChip) to facilitate the growth of unculturable aquatic bacterial community. cChip was optimized for microbial growth using known bacteria in the lab, later, microbes from a freshwater lake were concentrated (instead of using the traditional dilution method) and inoculated in cChip before incubating the chip in simulated lake environment. Then further sub-culturing was done on laboratory media. The field samples were also analyzed using traditional culturing and metagenomics for a comparison. Results: Metagenomics analysis showed that 832 microbial species were present in the samples belonging to five different phyla, that is, Cyanobacteria, Proteobacteria, Actinobacteria, Bacteroidetes and Verrucomicrobia. However, traditional culturing yielded only 36 isolates that belonged to four different phyla, that is, Actinobacteria, Proteobacteria, Firmicutes and Bacteroidetes. Culturing through cChip yielded 154 isolates belonging to five different phyla, that is, Proteobacteria, Actinobacteria, Bacteroidetes, Verrucomicrobia and Firmicutes. Out of these 154 cChip isolates, 45 were previously uncultured bacteria having a 16S rRNA gene similarity from 91.35 % to 98.7 % to their closest relatives according to NCBI GenBank. Conclusion: This study shows that culturing microorganisms in the cChip from aquatic environment using concentration process before performing the traditional petri plate culturing can result in the successful growth of unculturable bacteria. To the best of our knowledge this is the first study conducted for successful exploration of unculturable aquatic microbial community. This study can have a significant impact on our understanding of the techniques that can be applied for exploring the unexplored microbiome from diverse environments. We also hypothesize that certain modifications in the manufacturing material, keeping the design and techniques of this study intact can result in the application of this technique from gut microbiome to extremophiles in the environment.
Carbon Fluxes Over an Even-Aged Pure Masson pine (Pinus Massoniana) Stand
Authors: Tan Zheng-Hong , Ding Fang-Jun , Liu Yan-Hui , Wu Peng , Zhao Wen-Jun , Yu Rui , Jiang Long , Yang Lian-Yan
Published: October 2020

Masson pine (Pinus massoniana) is a tree species widely planted in central and south China. In the present pioneer study, we reported about our two years of carbon flux observations over an even-aged pure Masson pine stand. Light intensity could explain nearly half (47%) of the variance in daytime net ecosystem exchange (NEE). Daytime dark respiration was lower than nighttime NEE, suggesting a possible effect of light inhibition on respiration. The mean annual NEE was -557 g C m-2 yr-1, which indicated that this stand is a medium to large carbon sink. This NEE estimates were defensive because we checked the data with thorough quality controls and in consistency with previous independent estimates. An unexpected seasonal pattern of NEE was observed with a clear reduction around the transitional period between summer and autumn (around July). This NEE reduction is probably a consequence of water stress induced stomatal control, and not of a decrease in light intensity. The updated optimal stomatal theory did not provide the best description of stomatal control in relation to photosynthesis. Whether this is a new emergent property of the ecosystem scale needs further investigation.
Circulating Exosomal MicroRNAs as Diagnostic and Prognostic Biomarkers in Patients with Diffuse Large B-cell Lymphoma
Authors: Cao Di , Jiang Yu , Cao Xia , Li Mao , Jing Caixia , Feng Yu , Xu Juan , Zheng Yuhuan , Kang Deying , Xu Caigang
Published: October 2020

Background: Exosomal microRNAs (miRNAs) are potential biomarkers for a variety of tumors but have not yet been tested in diffuse large B-cell lymphoma (DLBCL). Here we sought to determine whether circulating exosomal miRNAs are differentially expressed in the blood of DLBCL patients compared with those in the blood of non-DLBCL patients with lymphoma and healthy subjects. In addition, we sought to explore whether circulating exosomal miRNAs could be used as prognostic predictors for DLBCL patients. Methods: Circulating exosomal miRNAs were isolated and used to perform miRNA expression profiling using quantitative reverse transcription polymerase chain reaction (qRT-PCR) based on Exiqon microarray from 10 DLBCL patients and 5 healthy subjects. Using qRT-PCR, miRNA candidates were first evaluated in the testing stage (24 DLBCL patients vs. 24 healthy subjects) and further confirmed in validation stage(99 DLBCL patients vs. 65 healthy subjects). Meanwhile, we also explored miRNAs concentrations in 29 non-DLBCL lymphoma cases, which were enrolled as concurrent control in this study. And lastly, relationships between miRNA level and patient outcomes including overall survival (OS) and progression-free survival (PFS) were studied. Results: Five circulating exosomal miRNAs (miR-379-5p, miR-135a-3p, miR-4476, miR-483-3p and miR-451a) were differently expressed in DLBCL patients compared with healthy controls. The 5-miRNA panel enabled us to predicted the probability of a diagnosis of DLBCL with an area under curve(AUC) of 0.863. Four circulating exosomal miRNAs (miR-379-5p, miR-135a-3p, miR-155-5p and miR-451a) were differently expressed between DLBCL patients and concurrent controls, the AUC of this 4-miRNA panel in distinguishing DLBCL patients from concurrent controls was 0.775. One miRNA, namely miR-451a, was significantly associated with both PFS and OS of DLBCL patients in the univariate analysis, and still statistically significant after adjusting for the International Prognostic Index(IPI) in the multivariate analysis. The combination of circulating miR-451a with IPI had a better predication for PFS and OS. Conclusions: Our study suggested subsets of circulating exosomal miRNAs could be useful noninvasive biomarkers for the diagnosis of DLBCL and the use of circulating exosomal miRNA improves the identification of patients with newly diagnosed DLBCL with poor outcomes.