bluuebunny/crossref_metadata_2025_split huggingface dataset:
Are activated B cells involved in the process of myocardial fibrosis after acute myocardial infarction? An in vivo experiment
Authors: Mo Fanrui , Luo Ying , Yan Yuluan , Li Juan , Lai Shayi , Wu Weifeng 
Published: October 2020

Abstract
Background Inflammatory cells infiltrate into the ischemic and hypoxic myocardial tissue after myocardial infarction. B cells gather at the site of myocardial injury and secrete cytokines to regulate immune inflammation and fiber repair processes. Methods The animal experiment used ligation of the left anterior descending (LAD) artery of C57BL/6 mice to establish a mouse acute myocardial infarction (AMI) model to observe changes in activated B cells and cytokines at different time points. Twelve-week-old C57BL/6 male mice were randomly divided into the Sham group (24 mice) (thread under the LAD artery without ligation) and the AMI group (64 mice). In addition, C57BL/6 B-cell knockout (BKO) mice and C57BL/6 wild-type (WT) mice were used to establish AMI models to observe the expression levels of cardiomyocyte cytokines, such as TNF-α IL-1β, IL-6, TGF-β1, COL1-A1, COL3-AIII, TIMP, and MMP9. Moreover, pathological and collagen changes in the myocardium were analysed. One-way ANOVA and LSD method was used for comparisons of multiple and pairwise groups respectively. P<0.05 indicated significant differences. Results An AMI model of C57BL/6 mice was established successfully. The ratio of activated B cells and the expression of TNF-α, IL-1β, IL-6, TGF-β1, and B cell activating factor (BAFF) in the 5-day subgroup were the highest in the myocardium, spleen and peripheral blood with the most obvious myocardial inflammatory cell infiltration. The cytokines mRNA expression levels in the 5-day subgroup of the BKO group were decreased compared with those in the WT group (P<0.05). Among the 2-week subgroups of the Sham, WT and BKO groups, the the LVEDd and LVESd of the BKO group were lower than those of the WT group (P<0.05), and the left ventricular ejection fraction (LVEF) was higher than that of the WT group (P<0.05). Conclusion Activated B cells participate in the sustained state of myocardial inflammation and immune system activation after AMI, and may affect the metabolism of myocardial collagen after AMI by secreting cytokines. Moreover, B cells promote the expression of myocardial collagen Type I and Type III and damage the left ventricular ejection function.
Network pharmacology based research into the effect and mechanism of Yinchenhao Decoction against Cholangiocarcinoma
Authors: Chen Zhiqiang , Lin Tong , Liao Xiaozhong , Li Zeyun , Lin Ruiting , Qi Xiangjun , Chen Guoming , Sun Lingling , Lin Lizhu 
Published: October 2020

Abstract
Background

This study aimed to screen out the effective active components of Yinchenhao decoction (YCHD) using network pharmacology, estimate their potential targets, screen out the pathways, as well as delve into the potential mechanisms on treating cholangiocarcinoma.

Methods

By the traditional Chinese medicine system pharmacology database and analysis platform (TCMSP) as well as literature review, the major active components and their corresponding targets were estimated and screened out. Using the software Cytoscape 3.6.0, a visual network was established using the active components of YCHD and the targets of cholangiocarcinoma. Based on STRING online database, the protein interaction network of vital targets was built and analyzed. With the Database for Annotation, Visualization, and Integrated Discovery (DAVID) server, the gene ontology (GO) biological processes and the Kyoto encyclopedia of genes and genomes (KEGG) signaling pathways of the targets enrichment were performed. The AutoDock Vina was used to perform molecular docking and calculate the binding affinity. The PyMOL software was utilized to visualize the docking results of active compounds and protein targets. In vivo experiment, the IC 50 values and apoptosis rate in PI-A cells were detected using CCK-8 kit and Cell Cycle Detection Kit. The predicted targets were verified by the real-time PCR and western blot methods.

Results

32 effective active components with anti-tumor effects of YCHD were sifted in total, covering 209 targets, 96 of which were associated with cancer. Quercetin, kaempferol, beta-sitosterol, isorhamnetin, and stigmasterol were identified as the vital active compounds, and AKT1, IL6, MAPK1, TP53 as well as VEGFA were considered as the major targets. The molecular docking revealed that these active compounds and targets showed good binding interactions. These 96 putative targets exerted therapeutic effects on cancer by regulating signaling pathways (e.g., hepatitis B, the MAPK signaling pathway, the PI3K-Akt signaling pathway, and MicroRNAs in cancer). Our in vivo experimental results confirmed that YCHD showed therapeutic effects on cholangiocarcinoma by decreasing IC 50 values, down-regulating apoptosis rate of cholangiocarcinoma cells, and lowering protein expressions.

Conclusion

As predicted by network pharmacology strategy and validated by the experimental results, YCHD exerts anti-tumor effects through multiple components, targets, and pathways, thereby providing novel ideas and clues for the development of preparations and the treatment of cholangiocarcinoma.
Paracrine stimulation of perinatal lung functional and structural maturation by mesenchymal stem cells.
Authors: Obendorf Janine , Fabian Claire , Thome Ulrich H. , Laube Mandy 
Published: October 2020

Abstract
Background: Mesenchymal stem cells (MSCs) were shown to harbor therapeutic potential in models of respiratory diseases, such as Bronchopulmonary Dysplasia (BPD), the most common sequel of preterm birth. In these studies cells or animals were challenged with hyperoxia or other injury-inducing agents. However, little is known about the effect of MSCs on immature fetal lungs and whether MSCs are able to improve lung maturity, which may alleviate lung developmental arrest in BPD. Methods: We aimed to determine if conditioned medium (CM) of MSCs stimulates functional and structural lung maturation. As a measure of functional maturation, Na + transport in primary fetal distal lung epithelial cells (FDLE) was studied in Ussing chambers. Na + transporter and surfactant protein mRNA expression was determined by qRT-PCR. Structural maturation was assessed by microscopy in fetal rat lung explants. Results: MSC-CM strongly increased the activity of the epithelial Na + channel (ENaC) and the Na,K-ATPase as well as their mRNA expression. Branching and growth of fetal lung explants, and surfactant protein mRNA expression were enhanced by MSC-CM. Epithelial integrity and metabolic activity of FDLE cells were not influenced by MSC-CM. Since MSC’ actions are mainly attributed to paracrine signaling, prominent lung growth factors were blocked. None of the tested growth factors (VEGF, BMP, PDGF, EGF, TGF-β, FGF, HGF) contributed to the MSC-induced increase of Na + transport. In contrast, inhibition of PI3-K/AKT and Rac1 signaling reduced MSC-CM efficacy, suggesting an involvement of these pathways in the MSC-CM-induced Na + transport. Conclusion: The results demonstrate that MSC-CM strongly stimulated functional and structural maturation of fetal lungs. These effects were at least partially mediated by the PI3-K/AKT and Rac1 signaling pathway. Thus MSCs not only repair a deleterious tissue environment, but also target lung cellular immaturity itself.
The prospects for sustaining evidence-based responses to the US opioid epidemic: State leadership perspectives
Authors: Caton Lauren , Yuan Mina , Louie Dexter , Gallo Carlos , Abram Karen , Palinkas Lawrence , Brown C Hendricks , McGovern Mark 
Published: October 2020

Abstract
Background: The US 21st Century Cures Act provided $7.5 billion in grant funding to states and territories for evidence-based responses to the opioid epidemic. Currently, little is known about optimal strategies for sustaining these programs beyond this start-up funding. Methods: Using an inductive, conventional content analysis, we conducted key informant interviews with former and current state leaders (n=16) about barriers/facilitators to sustainment and strategies for sustaining time-limited grants. Results: Financing and reimbursement, service integration, and workforce capacity were the most cited barriers to sustainment. Status in state government structure, public support, and spending flexibility were noted as key facilitators. Effective levers to increase chances for sustainment included strong partnerships with other state agencies, workforce and credentialing changes, and marshalling advocacy through public awareness campaigns.Conclusions: Understanding the strategies that leaders have successfully used to sustain programs in the past can inform how to continue future time-limited, grant-funded initiatives.
Diversities of antimicrobial resistance patterns across Staphylococcus aureus and Coagulase-Negative Staphylococci isolated from dairy herbs in Jiangsu province, China
Authors: Jin Weijie , Lin Weidong , Feng Qing , Zhang Dashuai , Yang Juan , Qin Aijian 
Published: October 2020

Abstract
Background

As mastitis major causing agents, Coagulase-Negative Staphylococci (CNS) and Staphylococcus aureus (SA), are important and their connections are special and worth comparing. The overall aim of this study is to investigate antimicrobial resistance patterns of CNS and SA. Understanding the special characters of staphylococci is essential for finding the precise strategies or directions against them.
Results

Staphylococci (47.63%) were the commonest pathogens in subclinical mastitis in Jiangsu province. 73.34% and 45.78% of CNS respectively were extensively drug-resistant (XDR) strains and multiple drug-resistant (MDR) strains, mainly resisting penicillin (77.78%) and ceftazidime (55.95%); for SA, 62.52% of them were MDR strains and resistant to penicillin (94.05%) and norfloxacin (58.33%). Notably, 4 CNS were pandrug-resistant (PDR) strains. According to the chi-square test results, we summary and find that SA was more resistant to quinolones (ciprofloxacin, levofloxacin, and norfloxacin) and co-trimoxazole antibiotics than CNS, significantly; on the other hand, CNS were significantly more resistant to lincomycins (clindamycin), macrolides (including erythromycin and clarithromycin), tetracycline, and nitrofurantoin antibiotics than SA,, in total. Resistance genes were detected more frequently in CNS than SA; nearly a third of CNS resit penicillin by β-lactamase coded by blaZ and CNS resist tetracycline mainly by protein pump mechanism. For SA, blaZ was detected out 27.2%, and the other five resistance genes were rare to be found.
Conclusion

Responding to antibiotics interfering with metabolisms of nucleotide, SA might be more resistant than CNS; while CNS strains are more likely to become mutations to survive under the stress of antibiotics interfering with protein synthesis. These might provide the advantages for CNS to represent like a reservoir of resistance genes for other staphylococci as the previous researches’ assumption.
In vivo evidence of microstructural hypo-connectivity of brain white matter in 22q11.2 deletion syndrome
Authors: Raven Erika , Veraart Jelle , Kievit Rogier , Genc Sila , Ward Isobel , Cunningham Adam , Doherty Joanne , Bree Marianne van den , Jones Derek 
Published: October 2020

Abstract
22q11.2 Deletion Syndrome, or 22q11.2DS, is a genetic syndrome associated with high rates of schizophrenia, autism, and attention deficit hyperactivity disorder, in addition to widespread structural and functional abnormalities throughout the brain. Experimental animal models have identified neuronal connectivity deficits, e.g., decreased axonal length and complexity of axonal branching, as a primary mechanism underlying atypical brain development in 22q11.2DS. However, it is still unclear whether deficits in axonal morphology can also be observed in people with 22q11.2DS. Here, we provide an unparalleled in vivo characterisation of white matter microstructure in both typically-developing children and children with 22q11.2DS using a dedicated magnetic resonance imaging scanner which is sensitive to axonal morphology. By extracting a rich array of diffusion metrics, we present microstructural profiles of typical and atypical white matter development, and provide new evidence of connectivity differences between typically-developing and 22q11.2DS children. A recent, large-scale consortium study identified higher diffusion anisotropy and reduced overall mobility of water as hallmark microstructural alterations of white matter in 22q11.2DS, in particular for commissural fibers. We observed similar findings across all white matter tracts in this study, in addition to identifying deficits in axonal morphology. This, in combination with reduced tract volume measurements, supports the hypothesis that microstructural connectivity in 22q11.2DS is mediated by densely packed axons with disproportionately small diameters. Our findings provide insight into the in vivo mechanistic features of 22q11.2DS, and promote further investigation of shared features in neurodevelopmental and psychiatric disorders.
A rapid and efficient screening system for neutralizing antibodies and its application for SARS-CoV-2
Authors: Han Xiaojian , Wang Yingming , Li Shenglong , Hu Chao , Li Tingting , Gu Chenjian , Wang Kai , Shen Meiying , Wang Jianwei , Hu Jie , Wu Ruixin , Mu Song , Gong Fang , Chen Qian , Gao Fengxia , Huang Jingjing , Long Yingyi , Luo Feiyang , Song Shuyi , Long Shunhua , Hao Yanan , Li Luo , Wu Yang , Xu Wei , Cai Xia , Gao Qingzhu , Zhang Guiji , He Changlong , Deng Kun , Du Li , Nai Yaru , Wang Wang , Xie Youhua , Qu Di , Huang Ailong , Tang Ni , Jin Aishun 
Published: October 2020

Abstract
After the epidemic of COVID-19, neutralizing antibodies (NAbs) against SARS-CoV-2 has been developed for the preventative and therapeutic purposes. However, few methodologies are reported in detail on how to rapidly and efficiently generate NAbs of interest. Here, we present a strategically optimized screening method for NAbs, which has enabled us to obtain SARS-CoV-2 receptor-binding domain (RBD) specific monoclonal Abs within 4 days, followed by additional 2 days to evaluate their neutralizing activities. Using this method, we obtained 198 specific Abs against SARS-CoV-2 RBD from the blood samples of COVID-19 convalescent patients, and 96 of them showed neutralizing activity. At least 20% of these NAbs exhibited high neutralizing potency. The top 2 NAbs showed the half-maximal inhibitory concentration (IC50) to block authentic SARS-CoV-2 at 9.88 and 11.13 ng/ml, respectively. Altogether, our study provides a fundamental methodology for discovering NAbs with potential preventative and therapeutic value for emerging infectious diseases.
Upconverted excitation energy lock-in for deep-ultraviolet enhancement
Authors: Su Qianqian , Wei Han-Lin , Wang Shuai , Chen Chaohao , Ming Guan , Su Yan , Wang Haifang , Chen Zhigang , Jin Dayong 
Published: October 2020

Abstract
Photon upconversion of near-infrared (NIR) irradiation into deep-ultraviolet (UV) emission offers many exciting opportunities for drug release in deep tissues, photodynamic therapy, solid-state lasing, energy storage, and photocatalysis. However, NIR-to-deep-UV upconversion remains a daunting challenge due to low quantum efficiency. Here, we report an unusual six-photon upconversion process in Gd3+/Tm3+-codoped nanoparticles comprising a heterogeneous, core-multishell nanostructure. This multishell design efficiently suppresses energy consumption induced by interior energy traps, maximizes cascade sensitizations of the NIR excitation, and promotes upconverted deep-UV emission from high-lying excited states. We released the intense six-photon-upconverted UV emissions at 253 nm under 808-nm excitation. This work provides new insight into mechanistic understanding of the upconversion process within the heterogeneous architecture, while offering exciting opportunities for developing nanoscale deep-UV emitters that can be remotely controlled in deep tissues upon NIR illumination.
Long-term persistence of neutralizing memory B cells in SARS-CoV-2
Authors: Bull Rowena , Abayasingam Arunasingam , Balachandran Harikrishnan , Agapiou David , Rodrigo Chaturaka , Keoshkerian Elizabeth , Li Hui , Brasher Nicholas , Christ Daniel , Rouet Romain , Burnett Deborah , Grubor-Bauk Branka , Rawlinson William , Turville Stuart , Aggarwal Anupriya , Brilot Fabienne , Mina Michael , Post Jeffrey , Hudson Bernard , Gilroy Nicky , Dwyer Dominic , Sasson Sarah , Tea Fiona , Pilli Deepti , Tedla Nicodemus , Lloyd Andrew , Martinello Marianne 
Published: October 2020

Abstract
Considerable concerns relating to the duration of protective immunity against SARS-CoV-2 have been raised, with evidence of antibody titres declining rapidly after infection and reports of reinfection. Here we monitored antibody responses against SARS-CoV-2 receptor binding domain (RBD) for up to six months after infection. While antibody titres were maintained, half of the cohort’s neutralising responses had returned to background. However, encouragingly in a selected subset of 13 participants, 12 had detectable RBD-specific memory B cells and these generally increased out to 6 months. Furthermore, we were able to generate monoclonal antibodies with SARS-CoV-2 neutralising capacity from these memory B cells. Overall our study suggests that the loss of neutralising antibodies in plasma may be countered by the maintenance of neutralising capacity in the memory B cell repertoire.
Impact of a Pandemic on Surgical Neuro-Oncology - Maintaining Functionality in Crisis
Authors: Hameed N.U.Farrukh , Ma Yixin , Zhen Zili , Wu Shuai , Feng Rui , Li Weiping , Huang Guodong , Wu Jinsong , Chen Zhongping 
Published: October 2020

Abstract
Background: The Coronavirus disease 2019 (COVID-19) pandemic has extraordinarily impacted global healthcare. Neuro-oncological surgery units have peculiar features that make them highly relevant in the strategic reaction to the pandemic. In this Chinese Society of Neuro-Oncology (CSNO) initiated survey, we appraise the changes implemented in neurosurgery hospitals across different Asian countries and provide expert recommendations for responses at different stages of the pandemic.Methods: A 42-question survey was distributed to neurosurgery hospitals across different Asian countries by the CSNO on April 1, 2020, with responses closed on April 18, 2020.Results: 144 hospitals completed the questionnaire. Most were in WHO post-peak phase of the pandemic and reported a median reduction in neurosurgery volume of 25-50%. Most(67.4%) resumed elective surgery in only COVID-19 negative patients;11.1% performed only emergency cases irrespective of COVID-19 status;2.1% suspended all surgical activity. Ninety-one(63.2%) relocated personnel from neurosurgery to other departments. Fifty-two(36.1%) hospitals suspended post-operative adjuvant therapy and 94(65.2%) instituted different measures to administer post-operative adjuvant therapy. Majority(59.0%) of the hospitals suspended research activity. Most(70%) respondents anticipate that current neurosurgery restrictions will continue to remain for >1 month.Conclusions: Majority of the respondents to our survey reported reduced neurosurgery activity, policy modification, personnel reallocation, and curtailment of educational/research activities in response to the COVID-19 pandemic. The persistent widespread interruption of surgical neuro-oncology in even post-peak phases of the pandemic raises serious concerns about the long-term impact of the pandemic on neuro-oncological patients and highlights the essence of timely measures for pandemic preparedness, patient triage, and workforce protection.
Novel Adapter CAR-T cell Technology for precisely controllable Multiplex Cancer Targeting
Authors: Seitz Christian , Mittelstaet Joerg , Hau Jana , Reiter Selina , Illi Clara , Kieble Verena , Engert Fabian , Drees Britta , Bender Giulia , Atar Daniel , Krahl Ann-Christin , Knopf Philipp , Schroeder Sarah , Paulsen Nikolas , Rokhvarguer Alexander , Scheuermann Sophia , Rapp Elena , Mast Anna-Sophia , Rabsteyn Armin , Schleicher Sabine , Grote Stefan , Schilbach Karin , Kneilling Manfred , Pichler Bernd , Lock Dominik , Kotter Bettina , Dapa Sandra , Miltenyi Stefan , Kaiser Andrew , Lang Peter , Handgretinger Rupert , Schlegel Patrick 
Published: October 2020

Abstract
Chimeric antigen receptor (CAR)-T therapy holds great promise to sustainably improve cancer treatment. However, currently, a broad applicability of CAR-T cell therapies is hampered by limited CAR-T cell versatility and tractability and the lack of exclusive target antigens to discriminate cancerous from healthy tissues. To achieve temporal and qualitative control on CAR-T function, we engineered the Adapter CAR (AdCAR) system. AdCAR-T are redirected to surface antigens via biotin-labeled adapter molecules in the context of a specific linker structure, referred to as Linker-Label-Epitope. AdCAR-T execute highly specific and controllable effector function against a multiplicity of target antigens. In mice, AdCAR-T durably eliminate aggressive lymphoma. Importantly, AdCAR-T might prevent antigen evasion by combinatorial simultaneous or sequential targeting of multiple antigens and are capable to identify and differentially lyse cancer cells by integration of adapter molecule mediated signals based on multiplex antigen expression profiles.
Concepturealize™: A New Contribution to Generate Real-needs-focussed, User-centred, Lean Business Models
Authors: Allen Graeme 
Published: October 2020

Abstract
It is widely accepted that somewhere in the region of 90% to 95% of startups fail. It is often suggested that the majority of unsuccessful startups either failed to identify a viable idea, or they failed to execute the idea effectively enough to get to market before running out of cash. Two approaches stand out as being particularly well-suited to addressing these problems: Design Thinking and Lean Startup, respectively. This paper presents the Concepturealize™ methodology that crossapplies Design Thinking and Lean Startup as a single iterative process and that enables the entrepreneur to generate real-needs-focussed, user-centred, lean business models.