bluuebunny/crossref_metadata_2025_split huggingface dataset:
FZD2 Promotes TGF-β-induced Epithelial-to-Mesenchymal Transition in Breast Cancer via Activating Notch Signaling Pathway
Authors: Tuluhong Dilihumaer , Chen Tao , Wang Jingjie , Zeng Huijuan , Li Hanjun , Dunzhu Wangmu , Li Qiurong , Wang Shaohua 
Published: October 2020

Abstract
Background: Breast cancer (BC) is one of the commonest female cancers, which is characterized with high incidence. Although treatments have been improved, the prognosis of BC patients in advanced stages remains unsatisfactory. Thus, exploration of the molecular mechanisms underneath BC progression is necessary to find novel therapeutic methods. Frizzled class receptor (FZD2) belongs to Frizzled family, which has been proven to promote cell growth and invasion in various human cancers. The purpose of our study was to detect the functions of FZD2 and explore its mechanism in BC.Methods: The level of FZD2 was measured in BC tissues by quantitative real-time polymerase chain reaction (qRT-PCR), western blot, immunohistochemistry (IHC) respectively. Cell Counting Kit-8 (CCK-8), colony formation assay, transwell assays, wound healing assay and flow cytometry analyses were conducted separately to test cell viability, invasion, migration, apoptosis and cell cycle distribution. Epithelial-mesenchymal transition (EMT) biomarkers were determined by using Immunofluorescence assay. Xenograft tumorigenicity assay was performed to assess the effect of FZD2 on tumor growth in vivo.Results: FZD2 mRNA and protein expression was abundant in BC tissues. Moreover, high level of FZD2 had significant correlation with poor prognosis. In vitro functional assays revealed that silencing of FZD2 had suppressive effects on BC cell growth, migration and invasion. Animal study further demonstrated that FZD2 silencing inhibited BC cell growth in vivo. In addition, FZD2 induced EMT in BC cells in a transforming growth factor (TGF)-β1-dependent manner. Mechanistically, knockdown of FZD2 led to the inactivation of Notch signaling pathway.Conclusion: FZD2 facilitates BC progression and promotes TGF-β1-inudced EMT process through activating Notch signaling pathway.
Is oxygen therapy beneficial for normoxemic patients with acute heart failure? A propensity score matched study
Authors: Yu Yue , Yao Ren-qi , Zhang Yu-feng , Wang Su-yu , Xi Wang , Wang Jun-nan , Huang Xiao-yi , Yao Yong-ming , Wang Zhinong 
Published: October 2020

Abstract
Background: The clinical efficiency of routine oxygen therapy is uncertain in patients with acute heart failure (AHF) who do not have hypoxemia. The aim of this study was to investigate the association between oxygen therapy and clinical outcomes in normoxemic patients hospitalized with AHF using real-world data.Methods: Normoxemic patients diagnosed with AHF on ICU admission from the electronic ICU (eICU) Collaborative Research Database were included in the current study, in which the study population was divided into the oxygen therapy group and the ambient-air group. Propensity score matching (PSM) was applied to create a balanced covariate distribution between patients receiving supplemental oxygen and those exposed to ambient air. Linear regression and logistic regression models were performed to assess the associations between oxygen therapy and length of stay (LOS), and all-cause in-hospital as well as ICU mortality rates, respectively. A series of sensitivity and subgroup analyses were conducted to further validate the robustness of our findings.Results: A total of 2,922 normoxemic patients with AHF were finally included in the analysis. Overall, 42.1% (1,230/2,922) patients were exposed to oxygen therapy, and 57.9% (1,692/2,922) patients did not receive oxygen therapy (defined as the ambient-air group). After PSM analysis, 1,122 pairs of patients were matched: each patient receiving oxygen therapy was matched with a patient without receiving supplemental oxygen. The multivariable logistic model showed that there was no significant interaction between the ambient air and oxygen group for all-cause in-hospital mortality (odds ratio [OR] 1.30; 95% confidence interval [CI] 0.92-1.82; P＝0.138) or ICU mortality (OR 1.39; 95% CI 0.83-2.32; P＝0.206) in the post-PSM cohorts. In addition, linear regression analysis revealed that oxygen therapy was associated with prolonged ICU LOS (OR 1.11; 95% CI 1.06-1.15; P＜0.001) and hospital LOS (OR 1.06; 95% CI 1.01-1.10; P＝0.009) after PSM. Furthermore, the absence of an effect of supplemental oxygen on mortality was consistent in all subgroups.Conclusions: Routine use of supplemental oxygen in AHF patients without hypoxemia was not found to reduce all-cause in-hospital mortality or ICU mortality.
Genomic Variations in SARS-CoV-2 Strains at the Target Sequences of Nucleic Acid Amplification Tests
Authors: Cao Canhui , Yu Ruidi , Zeng Shaoqing , Liu Dan , Gong Wenjian , Li Ruyuan , Wang Siyuan , Yuan Yuan , Chi Jianhua , Liu Jiahao , Yu Yang , Jiao Xiaofei , Cai Guangyao , Jin Ning , Ye Fei , Gao Qinglei 
Published: October 2020

Abstract
Background
Nucleic acid amplification is the main method used to detect infections of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). However, the false-negative rate of nucleic acid tests cannot be ignored.
Methods
Herein, we demonstrated genomic variations at the target sequences for the tests and the geographical distribution of the variations across countries by analyzing the whole-genome sequencing data of SARS-CoV-2 strains from the 2019 Novel Coronavirus Resource (2019nCoVR) database.
Results
Among the 21 pairs of primer sequences in regions ORF1ab, S, E, and N, the total length of primer and probe target sequences was 938 bp, with 131(13.97%) variant loci in 2415 (38.96%) isolates. Primer targets in the N region contained the most variations that were distributed among the most isolates, and the E region contained the least. Single nucleotide polymorphisms were the most frequent variation, with C to T transitions being detected in the most variant loci. G to A transitions and G to C transversions were the most common and had the highest isolate density. Genomic variations at the three mutation sites N: 28881, N: 28882, and N: 28883 were the most commonly detected, including in 608 SARS-CoV-2 strains from 33 countries, especially in the United Kingdom, Portugal, and Belgium.
Conclusions
Our work comprehensively analyzed genomic variations on the target sequences of the nucleic acid amplification tests, offering evidence to optimize primer and probe target sequence selection, thereby improving the performance of the SARS-CoV-2 diagnostic test.
Enhanced cell survival and therapeutic benefits of IL-10-expressing multipotent mesenchymal stromal cells for muscular dystrophy
Authors: Kasahara Yuko Nitahara , Kuraoka Mutsuki , Oda Yuki , Kinoh Hiromi Hayashita , Takeda Shin’ichi , Okada Takashi 
Published: October 2020

Abstract
Background:Multipotent mesenchymal stromal cells (MSCs) are potentially therapeutic for muscle disease because they can accumulate at the sites of injury and are immunosuppressive. MSCs are attractive candidates for cell-based strategies that target diseases with chronic inflammation, such as Duchenne muscular disease (DMD). We focused on the IL-10 based anti-inflammatory properties and hypothesized that IL-10 could increase the typically low survival of MSCs by exerting a paracrine effect after transplantation.Methods:We developed a continuous IL-10 expression system of MSCs using an adeno-associated virus (AAV) vector. To investigate the potential benefits of AAV/IL-10 vector-transduced MSCs (IL-10-MSCs), we examined the cell survival rates in the skeletal muscles after intramuscular injection into mice and dogs. The systemic treatment of IL-10-MSCs derived from dental pulp (DPSCs) was comprehensively analyzed using the canine X-linked muscular dystrophy model in Japan (CXMDJ), which has a severe phenotype similar to DMD patients. Results:In vivo bioluminescence imaging analysis revealed higher retention of IL-10-MSCs injected into the hind-limb muscle of mice. In the muscles of dogs, myofiber-like tissue was formed after the stable engraftment of IL-10-MSCs. Repeated systemic administration of IL-10-DPSCs into CXMDJ model resulted in long-term engraftment of cells, slightly increased serum levels of IL-10. IL-10-hDPSCs showed remarkably reduced expression of pro-inflammatory MCP-1, and upregulated stromal-derived factor-1 (SDF-1). In fact, MRI and histopathology of the hDPSC-treated CXMDJ indicated the regulation of inflammation in the muscles, but not myogenic differentiation from treated cells. hDPSC-treated CXMDJ showed improved running capability, and recovery in tetanic force with concomitant increase in physical activity. Serum creatine kinase levels, which increased immediately after exercise, were suppressed in the IL-10-hDPSC-treated CXMDJ. Conclusions:In case of local injection, IL-10-MSCs could maintain the long-term engraftment status and facilitate associated tissue repair. In case of repeated systemic administration, IL-10-MSCs facilitated the long-term retention of the cells in the skeletal muscle and also protected muscles with physical damage-induced injury, which improved muscle dysfunction in DMD. We can conclude that the local and systemic administration of IL-10-producing MSCs offers potential benefits for DMD therapy, through the beneficial IL-10 paracrine effects involving SDF-1.
The prognostic value of the SOFA score in patients with COVID-19: a retrospective, observational study
Authors: Yang Zheng , Hu Qinming , Huang Fei , Xiong Shouxin , sun yi 
Published: October 2020

Abstract
Background
Patients with Coronavirus disease 2019 (COVID-19) have a high mortality rate, and thus, it is particularly important to predict the severity and prognosis of COVID-19. The Sequential Organ Failure Assessment (SOFA) score has been used to predict the clinical outcomes of patients with multiple organ failure requiring intensive care. Therefore, we retrospectively analyzed the clinical characteristics, risk factors, and relationship between the SOFA score and the prognosis of COVID-19 patients.
Methods
Clinical variables were compared between patients with mild and severe COVID-19. Univariate and multivariate logistic regression analyses were performed to identify the risk factors for severe COVID-19. The Cox proportional hazards model was used to analyze risk factors for hospital-related death. Survival analysis was performed by the Kaplan-Meier method, and survival differences were assessed by the log-rank test. Receiver operating characteristic (ROC) curves of the SOFA score in different situations were drawn, and the area under the ROC curve was calculated.
Results
The median SOFA score of all patients was 2 (IQR, 1–3). Patients with severe COVID-19 exhibited a significantly higher SOFA score than patients with mild COVID-19 [3 (IQR, 2–4) vs 1 (IQR, 0–1); P < 0.001]. The SOFA score increased the risk of severe COVID-19, with an odds ratio of 5.851 (95% CI: 3.044–11.245; P < 0.001). The area under the ROC curve (AUC) was used to evaluate the diagnostic accuracy of the SOFA score in predicting severe COVID-19 [cutoff value = 2; AUC = 0.908 (95% CI: 0.857–0.960); sensitivity: 85.20%; specificity: 80.40%] and the risk of death in COVID-19 patients [cutoff value = 5; AUC = 0.995 (95% CI: 0.985-1.000); sensitivity: 100.00%; specificity: 95.40%]. Regarding the 60-day mortality rates of patients in the two groups classified by the optimal cutoff value of the SOFA score (5), patients in the high SOFA score group (SOFA score ≥ 5) had a significantly greater risk of death than those in the low SOFA score group (SOFA score < 5).
Conclusion
The SOFA score could be used to evaluate the severity and 60-day mortality of COVID-19. The SOFA score may be an independent risk factor for in-hospital death.
Incidence and Outcome of Acute Myocardial Infarction in Patients with Aortic Dissection and Risk Factor Control
Authors: Liu Fang , Qian Si-Chong , Chen Mu-Lei , Wang Zhe , Yang Xin-Chun 
Published: October 2020

Abstract
Background
The contradiction of management modality between acute myocardial infarction(AMI) and aortic dissection(AD) may result in clinical catastrophe. Data on risk factors, incidence and outcome of AD and AMI are limited, and there have been no studies on the long-term outcomes of AMI in patients with AD. So we aimed to investigate long-term outcomes after AMI in patients with AD, and propose a useful diagnostic paradigm.
Methods
Consecutively enrolled patients with AD and AMI who were referred to our center from 2010 to 2017. Baseline patient characteristics, risk factors, all medical treatments, echocardiographic parameters, laboratory data and treatment were recorded. All patients were followed up from the first hospitalization until a first heart event, death or 17 March, 2018.
Results
0.13% in AMI and 7.49% in AD patients had a concomitant diagnosis of AD and AMI. The average patient age was 53.3 ± 12.1 years and 84.6% were male. The most prevalent vascular risk factors were hypertension (69.2%) and current smoker (64.1%). Of all the 39 patients, 66.7% were managed surgically. Overall in-hospital mortality was 10.3%. The 30-day and 5-year fatality rates were 23.1% and 35.9%, but were higher for female than for male(66.7% vs 30.3%, log-rank P = 0.045) on 5-year mortality. The overall survival of females was inferior to the males (log-rank P = 0.045).
Conclusions
Patients with AMI and AD exhibit high 5-year fatality rates. For these patients, surgical management tend to have lower mortality. Improved management of hypertension and smoking, may reduce future incidence rates.
Human-mouse chimeric Fragile X syndrome model reveals FMR1-dependent neuronal phenotypes
Authors: Krzisch Marine , Wu Hao , Yuan Bingbing , Whitfield Troy , Liu Shawn , Fu Dongdong , Garrett-Engele Carrie , Chang Aaron , Warren Stephen , Cacace Angela , Andrykovich Kristin , Rietjens Rosalie , Jain Bhav , Wallace Owen , Jaenisch Rudolf 
Published: October 2020

Abstract
Abnormal neuronal development in Fragile X syndrome (FXS) is poorly understood. Data on FXS patients remain scarce and FXS animal models have failed to yield successful therapies. In vitro models do not fully recapitulate the morphology and function of human neurons. Here, we co-injected neural precursor cells (NPCs) from FXS patient-derived and corrected isogenic control induced pluripotent stem cells into the brain of neonatal immune-deprived mice. The cells populated the brain and differentiated into neurons and astrocytes. Single-cell RNA sequencing of transplanted cells revealed upregulated excitatory synaptic transmission and neuronal differentiation pathways in FXS neurons. Immunofluorescence analyses showed accelerated maturation of FXS neurons, an increased proportion of Arc-positive FXS neurons and increased dendritic protrusion width of FXS striatal medium spiny neurons. Our data show faster maturation and suggest increased synaptic activity and synaptic strength of FXS transplanted neurons. This model provides new insights into the alterations in FXS neuronal development.
Development of a versatile and efficient C-N lyase platform for asymmetric hydroamination via computational enzyme redesign
Authors: Cui Yinglu , Wang Yinghui , Tian Wenya , Bu Yifan , Li Tao , Cui Xuexian , Zhu Tong , Li Ruifeng , Wu Bian 
Published: October 2020

Abstract
Although C-N bonds are ubiquitous in natural products, pharmaceuticals, and agrochemicals, biocatalysts that forge these bonds with high atom efficiency and enantioselectivity have primarily been limited to a few select enzymes. In particular, the use of ammonia lyases has emerged as a powerful strategy to access C-N bond formation through hydroamination reactions, which has no counterpart in traditional synthetic chemistry. However, the broad utility of ammonia lyases is rather restricted due to their narrow synthetic scope, and the conjugate addition of a matrix of nucleophilic donors to electrophilic acceptors remains a longstanding challenge. Herein, we report the computational redesign of aspartase, a highly specific ammonia lyase, to yield C-N lyases with unprecedented cross-compatibility of nonnative nucleophiles and electrophiles. A wide range of noncanonical amino acids (ncAAs) are afforded with excellent conversion (up to 99%), regioselectivity > 99%, and product enantiomeric excess > 99%, and the process is scalable under industrially relevant protocols (demonstrated in kilogram-scale synthesis). Furthermore, the redesigned enzymes can be facilely integrated in cascade reactions, as we demonstrated the synthesis of β-lactams with different substitution patterns at the N-1 and C-4 positions in a one-pot reaction. This versatile and efficient C-N lyase platform supports the preparation of diverse libraries of ncAAs and their derivatives and will present opportunities in medicinal chemistry and synthetic biology.
Divergent Rhodium-Catalyzed Electrochemical Vinylic C–H Annulation of Acrylamides with Alkynes
Authors: Xing Yi-Kang , Chen Xin-Ran , Yang Qi-Liang , Zhang Shuoqing , Guo Haiming , Hong Xin , mei Tian-Sheng 
Published: October 2020

Abstract
A Rh-catalyzed electrochemical vinylic C–H annulation of acrylamides with alkynes has been developed in an undivided cell, affording cyclic products in good to excellent yield. Divergent syntheses of α-pyridones and cyclic imidates are accomplished by employing N-phenyl acrylamides and N-tosyl acrylamides as substrates, respectively. Additionally, excellent regioselectivities are achieved when using unsymmetrical alkynes. This electrochemical process is environmentally benign compared to traditional transition metal-catalyzed C–H annulations because it avoids the use of stoichiometric metal oxidants. DFT calculations elucidated the reaction mechanism and origins of substituent-controlled chemoselectivity. The sequential C–H activation and alkyne insertion under rhodium catalysis leads to the seven-membered ring vinyl-rhodium intermediate. This intermediate undergoes either the classic neutral concerted reductive elimination to produce α-pyridones, or the ionic stepwise pathway to produce cyclic imidates.
COVID-19 Lockdown in Spain: Psychological impact is greatest on younger and vulnerable children.
Authors: Matalí-Costa Josep , Camprodon-Rosanas Ester 
Published: October 2020

Abstract
In 2020, quarantine home confinement measures were implemented in Spain to control a pandemic for the first time. The objective of this study is to assess both the psychological and social impact of that “lockdown” on different age groups of children and adolescents, and also the different strategies adopted by families in that situation. We collected data via an online questionnaire answered by 850 participants, parents of young people aged between 4 and 18, between 24th April and 8th May 2020. Our results show that living in a home smaller than 80 m2 is associated with an increased risk of presenting clinical symptoms of emotional or behavioural distress, with an odds ratio of 2.54 (95%CI: 1.07 - 6.02), p = 0.034; while increased age is a predictor of better psychological functioning during lockdown: coefficient of 0.25 (95%CI: 0.07 - 0.41), p = 0.004. Moreover, age is also a marker of higher scores on the scale of psychological symptoms, with a coefficient of 0.02 (95%CI: 0.01 - 0.04), p = 0.005. To conclude, younger children present poorer behavioural and emotional functioning and more symptoms of emotional distress than adolescents during lockdown. Living in a small home is a risk factor for presenting clinical symptoms. These findings should be taken into consideration when planning for future home confinement episodes and when considering preventative strategies in the realm of mental healthcare.
SLAM Negatively Regulates IL-21 Production in Tfh-Like Cells from Allergic Rhinitis Patients
Authors: Yang Jun , Geng Lina , Ma Yongming , Tang Xinyi , Peng Huiyong , Tian Jie , Xu Huaxi , Wang Shengjun 
Published: October 2020

Abstract
Background: Allergic rhinitis (AR) is characterized by type Ⅰ hypersensitivity that is mediated by IgE-induced humoral responses. It is known that follicular helper T cells (Tfh) comprise the key Th cell subset that promotes antibody production. Signaling lymphocytic activation molecule (SLAM) participates in the regulation of the differentiation and function of Tfh cells, but whether this regulation is involved in the pathogenesis of AR is unknown.Methods: CD4+CXCR5+ Tfh-like cells from peripheral blood were detected by flow cytometry. The levels of IL-21 and IgE in serum were tested by ELISA. Blood CD4+CXCR5+ Tfh-like cells were sorted and cultured with anti-SLAM mAb in vitro.Results: The frequencies of circulating CD4+CXCR5+ Tfh-like cells appeared virtually unchanged in AR patients, but the expression of SLAM and SLAM-associated protein (SAP) on circulating Tfh-like cells was significantly decreased. Meanwhile, the level of serum IL-21 was increased in AR patients, and there was a negative correlation between the levels of IL-21 and the expression of SLAM or SAP in CD4+CXCR5+ T cells. Treatment with anti-SLAM mAb resulted in the reduced production of IL-21 by Tfh-like cells in vitro. Additionally, the expression of SLAM on B cells significantly decreased, although the percentages of B cells were increased in AR patients.Conclusions: SLAM negatively regulates the production of IL-21 in CD4+CXCR5+ Tfh-like cells, which contributes to the pathogenesis of AR.
The Optimal Changing Frequency of Hospital Privacy Curtains Based on Contamination Rates: A Prospective Culture Study
Authors: Lee Chan Mi , Goh Hye Yeon , Lee Hyo Yeon , Oh Young Rok , Park Wan Beom , Kim Nam Joong 
Published: October 2020

Abstract
To estimate contamination rates over time, we obtained cultures from 34 hospital privacy curtains and two control curtains over 8 weeks. If cultures revealed microorganisms over 2.5 colony forming unit (CFU)/cm2, we defined the curtains as contaminated. The burden of microorganisms of control curtains remained under 0.2 CFU/cm2 over the study period. The cumulative contamination rate of hospital privacy curtains increased over time (15.6% at week 2, 37.0% at week 4, and 55% at week 8). Contamination rates showed a tendency to increase as the number of beds in a room increased. We suggest that hospital curtains should be changed every 4 weeks, or less if the number of beds is high.