bluuebunny/crossref_metadata_2025_split huggingface dataset:
Melatonin Promotes Bone Marrow Mesenchymal Stem Cell Osteogenic Differentiation and Prevents Osteoporosis Development Through Modulating circ_0003865 that Sponges miR-3653-3p
Authors: Wang Xudong , Chen Taiqiu , Deng Zhihuai , Gao Wenjie , Liang Tongzhou , Qiu Xianjian , Gao Bo , Wu Zizhao , Qiu Jincheng , Zhu Yuanxin , Chen Yanbo , Liang Zhancheng , Zhou Hang , Xu Caixia , Liang Anjing , Su Peiqiang , Peng Yan , Huang Dongsheng 
Published: August 2020

Abstract
Background: To investigate circRNAs in Melatonin (MEL)-regulated bone marrow mesenchymal stem cell (BMSC) differentiation and osteoporosis.Methods: BMSC osteogenic differentiation was measured by qRT-PCR, western blot (WB), Alizarin Red and alkaline phosphatase (ALP) staining. Differential circRNA and mRNA profiles of BMSCs treated by MEL were characterized by deep sequencing, followed by validation using RT-PCR, Sanger sequencing, and qRT-PCR. Silencing and overexpression of circ_0003865 were conducted for functional investigations. The sponged microRNAs and targeted mRNAs were predicted by bioinformatics and validated by qRT-PCR, RNA pull-down, and dual-luciferase reporter assay. The function of miR-3653-3p and circ_0003865/miR-3653-3p/growth arrest-specific gene 1 (GAS1) cascade were validated for the osteogenic differentiation of BMSCs by qRT-PCR, WB, Alizarin Red, and ALP staining. The effects of circ_0003865 on osteoporosis (OP) development was tested in murine osteoporosis model.Results: MEL promoted osteogenic differentiation of BMSCs. RNA sequencing revealed significant alterations in circRNA and mRNA profiles associated with multiple biological processes and signaling pathways. Circ_0003865 expression in BMSCs was significantly decreased by MEL treatment. Silencing of circ_0003865 promoted osteogenic differentiation of BMSCs. Overexpression of circ_0003865 abrogated the promotion of BMSCs osteogenic differentiation induced by MEL. Furthermore, circ_0003865 sponged miR-3653-3p to promote GAS1 expression in BMSCs. BMSC osteogenic differentiation was enhanced by miR-3653-3p overexpression. By contrast, miR-3653-3p silencing mitigated the promoted BMSC osteogenic differentiation caused by circ_0003865 silencing. Finally, circ_0003865 silencing repressed OP development in mouse model.Conclusion: MEL promotes BMSC osteogenic differentiation and inhibits osteoporosis pathogenesis by suppressing the expression of circ_0003865, which regulates GAS1 gene expression via sponging miR-3653-3p.
Research on Coupling Vibration Mechanism Based on Contact System
Authors: HUANG Kepeng , Wang Fa-Zhan , Zhao Ming-Ji , Guo Bao-Liang , Ou Da-Quan 
Published: August 2020

Abstract
Aiming at the problem of vibration and bounce caused by the collision and contact of the moving and static contacts of the electrical switching device during the closing process, based on the comprehensive consideration of the nonlinear electromagnetic force and the collision contact force, the two-degree-of-freedom coupled motion differential equation of the contact system is established, and to solve and experimental analysis. The theoretical and experimental results show that the contact has not separated after the collision, and the iron core has collided, which further intensifies the contact bounce; when the iron core bounces for the second time, it does not affect the bounce of the contact; the contactor is in operation In this case, the movement of the moving iron core will cause slight jitter of the system. The research results provide a theoretical basis for further control and reduction of contact bounce.
Quality of Life of Children With Spinal Muscular Atrophy and Their Caregivers: A Chinese Cross-sectional Study
Authors: Yao Mei , Ma Ying , Qian Ruiying , Xia Yu , Yuan Changzheng , Bai Guannan , Mao Shanshan 
Published: August 2020

Abstract
Background: Spinal muscular atrophy (SMA) is an autosomal recessive motor neuron disease leading to multiple organs dysfunction, which can impair the quality of life (QoL) of patients and family. We aimed to evaluate QoL of children with SMA and their caregivers, and to assess the associated factors in a Chinese cross-sectional study.Methods: 101 caregivers and children aged 0-14 years with SMA were recruited from a children hospital. 26 children had type I SMA, 56 type II and 19 type III. Children’s QoL was measured by the Pediatric Quality of Life Inventory 3.0 Neuromuscular Module (PedsQL NMM) that was filled by caregivers. Caregiver’s QoL was measured by the Pediatric Quality of Life Inventory Family Impact Module (PedsQL FIM). Information on sociodemographic, disease-specific characteristics, and treatments were collected by the proxy-reported questionnaire. Two independent t-tests and one-way ANOVA were applied to compare differences in scores of QoL across subgroups.Results: Children with type III SMA had higher total score of PedsQL NMM, and scores in neuromuscular disease and family resources domain than those with type I and type II SMA (p < 0.001). Caregivers of children with type III SMA reported higher scores in domains of physical, emotional, social, and cognitive function of PedsQL FIM than those of children with types I and II (p < 0.05). In addition, disease-related characteristics (e.g. limited mobility, motor degeneration, skeleton deformity, and digestive system dysfunction) and respiratory support were associated with lower scores of PedsQL NMM and PedsQL FIM (p < 0.05). Exercise training, multidisciplinary team management and using the medication nusinersen were associated with higher scores of QoL in both PedsQL NMM and FIM (p < 0.05). Conclusion: Our study has demonstrated the factors that may impair or improve QoL of children patients with SMA and their parents. Particularly, QoL was relatively poor in children with type I and type II SMA as well as in their caregivers than those with type III SMA. Our study called for attention from clinical physicians on measuring QoL in their clinical practices in order to enhance the understanding of impacts of SMA and make better decisions regarding treatment.
On the origin of oldest Iron-Oxide-Copper-Gold (IOCG) deposits at the transition from Archean drip to plate tectonics
Authors: Ganade Carlos E , Griffin William L. , Weinberg Roberto F. , Belousova Elena , Takenaka Lynthener B. , Lopes Leonardo L. , Lacasse Christian M. , Campos Leandro D. 
Published: August 2020

Abstract
Geological evidence supports a significant change in Earth’s behaviour in the mid- to late Archaean, between 3.2 and 2.5 Ga, reflecting stabilization of the lithosphere and replacement of vertical tectonics by linear imbricated belts. At the heart of this change, the oldest (c. 2.75 Ga) Iron-Oxide-Copper-Gold deposits (IOCG) were formed in the Carajás Mineral Province (CMP) of the Amazon craton. U-Pb ages, Lu-Hf isotopes and trace element composition of detrital zircons from modern drainages record the crystallization ages of the exposed rocks of the CMP. Combined with the geochemistry of Archean granitoids in the CMP, we recognize four different age and compositional groups: 3.01-2.92 Ga TTG, 2.87-2.83 Ga transitional TTG + sanukitoid + K-rich granitoids, 2.78-2.72 Ga A-type crustal granites accompanying IOCGs, and 2.59-2.53 Ga alkaline high-K intrusions accompanied by renewed IOCG mineralization. The first two groups have a dominantly juvenile isotopic signature whereas the last two have evolved Hf-isotope signatures, accompanied by increase in K2O/Na2O, reflecting addition of old crustal components in the melting sources over time. The older juvenile granitoids are associated with dome-and-keel structures typical of granite-greenstone terranes, whereas the younger granitoids were emplaced along a linear shear belt associated with new mafic-ultramafic intrusions and remelting of older TTG. Based on the tectono-magmatic evolution, we argue that metasomatism and fertilization of the underlying lithospheric mantle by incompatible elements, necessary for the development of IOCG deposits, were related to vertical drip-tectonics during development of the TTG proto-continent. This proto-continent made the lithosphere rigid enough to allow linear translithospheric deformation to localize at c. 2.85 Ga, allowing decompression melting of the metasomatized lithospheric mantle in a restricted extensional setting to form abundant mafic and A-type granitoids at c. 2.75 Ga, and the first IOCG deposits on Earth.
Identification of novel mutations in SARS-COV-2 isolates from Turkey
Authors: Rehman Shazia , Mahmood Tariq , Aziz Ejaz , Batool Riffat 
Published: August 2020

Abstract
Severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2), originally emerged from Wuhan, has caused an unprecedented worldwide pandemic in the first half of 2020. Since the first report of SARS-CoV-2 on March 10th, 2020 in Turkey, more than 150,000 people in the country have been infected with this virus. In this study, a total of 80 genomic virulent strains from Turkey which were uploaded in NCBI and GISAID database were analyzed with other genomic sequences from different countries with the aim to characterize notable genomic features of SARS-CoV-2 and to identify some novel mutations. Consistent with other studies, the combination of variants at positions C3037T, C14408T and A23403G were most common mutations (73%), that exist together in isolates from Turkey. Our secondary structure prediction analysis also highlighted 11 unique non-substitutional mutations from viral SARS-COV-2 isolates of Turkey in different regions such as in spike (S) protein and non-structural proteins (Nsp2, Nsp3, NSP4, and NSP12/RdRP). Of these 11 mutations, nine of them have been found to be involved in structural alterations at different sites. 3/9 mutants (A771V, T1238I and G1251V) cause alteration in structure of S protein, while the rest of them induces structural changes in Nsp2 (A206T, R207C, T265I), Nsp3 (A1824V), Nsp4 (M2796I) and NSP12 (A4489V). These mutations identified here might have significant functional implications that needs to be addressed for future studies in the context of vaccine engineering and therapeutic interventions. Moreover, transmission and phylogenetic analysis revealed multiple independent sources of introductions for infection of hCovs in Turkey and close phylogenetic relationship of Turkish strains with Saudi strains.
Phyllosphere Microbiome in Response to Citrus Melanose
Authors: Li Pudong , Xu Jianping , Wang Zhengyi , Li Hongye 
Published: August 2020

Abstract
Background: Like microbiomes in the rhizosphere, phyllosphere microbiomes can have an important role in plant growth and health. However, whether and how the phyllosphere microbiomes respond to the invasion of pathogens is not well understood. In this study, we address this question using the citrus phyllosphere-associated microbiome as a model.Results: Through DNA metabarcoding (16S for bacteria and ITS for fungi) and shotgun metagenomic sequencing, we found that phyllosphere microbiomes in different ecological habitats (epiphytes and endophytes) responded differently to melanose disease caused by the fungal pathogen Diaporthe citri on citrus (Citrus unshiu) leaves. We observed that citrus phyllosphere-associated microbiome responded to the melanose disease in five ways: (1) increasing microbial richness; (2) reducing community evenness; (3) enriching selected microbes; (4) enhancing microbial interactions; and (5) enriching functional features involved in metabolism and fungal cell wall degrading.Conclusions: Our study revealed how phyllosphere microbiomes in the epiphytic and endophytic habitats differ between diseased and healthy leaves. Based on the differences at both the taxonomic and functional levels, we propose a general conceptual paradigm to describe the different microbial community assembly processes for the phyllosphere microbiome in response to leaf disease and how such processes impact plant health. Our results provide novel insights for understanding the contributions of the phyllosphere microbial community response during pathogen invasion.
Dictionary-Based Classification of Tweets About Environment
Authors: Cameletti Michela , Fabris Silvia , Schlosser Stephan , Toninelli Daniele 
Published: August 2020

Abstract
In the era of social media, the huge availability of digital data (e.g. posts sent through social networks or unstructured data scraped from websites) allows to develop new types of research in a wide range of fields. These types of data are characterized by some advantages such as reduced collection costs, short retrieval times and production of almost real-time outputs. Nevertheless, their collection and analysis can be challenging. For example, particular approaches are required for the selection of posts related to specific topics; moreover, retrieving the information we are interested in inside Twitter posts can be a difficult task.The main aim of this paper is to propose an unsupervised dictionary-based method to filter tweets related to a specific topic, i.e. environment. We start from the tweets sent by a selection of Official Social Accounts clearly linked with the subject of interest. Then, a list of keywords is identified in order to set a topic-oriented dictionary. We test the performance of our method by applying the dictionary to more than 54 million geolocated tweets posted in Great Britain between January and May 2019.
Evaluation of a Multidisciplinary Lipid Clinic to Improve the Care of Individuals With Severe Lipid Conditions: a RE-AIM Framework Analysis
Authors: Jones Laney K , McMinn Megan , Kann David , Lesko Michael , Sturm Amy C. , Walters Nicole , Chen Nan , Fry Kerrianne , Brownson Ross C. , Gidding Samuel S. , Williams Marc S. , Rahm Alanna Kulchak 
Published: August 2020

Abstract
Background. Individuals with complex dyslipidemia, or those with medication intolerance, are often difficult to manage in primary care. They require the additional attention, expertise, and compliance counseling that occurs in multidisciplinary lipid clinics (MDLCs). We conducted a program evaluation of the first year of a newly implemented MDLC utilizing the RE-AIM (reach, effectiveness, adoption, implementation, and maintenance) framework to provide empirical data not only on program effectiveness, but also on components important to local sustainability and future generalizability.Methods. The purpose of the MDLC is to increase uptake of guideline-based care for lipid conditions. Established in 2019, the MDLC provides care via a centralized clinic location within the healthcare system. Primary care providers and cardiologists were invited to refer individuals with lipid conditions. Using a pre/post study design, we evaluated implementation outcomes from the MDLC using the RE-AIM framework.Results. In 2019, 420 referrals were received, and 83 patients were seen in the MDLC (reach). In the lipid subgroups, we found improved diagnosis of condition, increase in prescribing of more aggressive lipid-lowering therapies, high rates of medication prior authorization approvals, and significant reductions in lipid levels (effectiveness). Of the 796 active primary care and cardiology providers in 2019, only 18% (146/796) referred patients to the MDLC (adoption). At the patient-level, 50% (41/82) of patients had at least one follow-up visit with the MDLC, with 12% (10/82) having two or more follow-up visits in 2019 (implementation). At the provider-level, an average of 35 patient referrals per month were made from primary care providers or cardiologists (SD 12) (implementation). During monthly meetings of the operational team, the decision to transition from in-person follow-up to telehealth appointments was implemented to increase capacity and sustain the clinic (maintenance).Conclusions. We found improved diagnosis and risk stratification, increase in guideline-recommended treatments prescribed and clinically significant lowering of lipid levels. Attention to factors including multiple points of contact, duration of visits, extraneous comorbidities and social support could aid in better understanding the success of patient outcomes.
Aptamer Targeted Therapy Potentiates Immune Checkpoint Blockade in Triple-Negative Breast Cancer
Authors: Camorani Simona , Passariello Margherita , Agnello Lisa , Esposito Silvia , Collina Francesca , Cantile Monica , Bonito Maurizio Di , Ulasov Ilya V. , Fedele Monica , Zannetti Antonella , De Lorenzo Claudia , Cerchia Laura 
Published: August 2020

Abstract
Background: Triple-negative breast cancer (TNBC) is a uniquely aggressive cancer with high rates of relapse due to resistance to chemotherapy, the current major option for treatment. TNBC expresses higher levels of programmed cell death-ligand 1 (PD-L1) compared to other breast cancers, providing the rationale for the recently approved immunotherapy with anti-PD-L1 monoclonal antibodies (mAbs). A huge effort is dedicated to identify actionable biomarkers that may allow for novel combination therapies with immune-checkpoint blockade in TNBC. Platelet-derived growth factor receptor β (PDGFRβ) is highly expressed in mesenchymal invasive TNBC, both on tumor cells and tumor microenvironment (TME). We recently proved that tumor growth and lung metastases are impaired in mouse models of human TNBC by a high efficacious PDGFRβ aptamer. Hence, we aimed at investigating the effectiveness of a novel combination treatment with the PDGFRβ aptamer and anti-PD-L1 mAbs in TNBC.Methods: The targeting ability of the anti-human PDGFRβ aptamer toward the murine receptor was verified by streptavidin-biotin assays and confocal microscopy, and its inhibitory function by transwell migration assays on PDGFRβ-positive cells. The anti-proliferative effects of the PDGFRβ aptamer/anti-PD-L1 mAbs combination was assessed in human MDA-MB-231 and murine 4T1 TNBC cells, both grown as monolayer or co-cultured with lymphocytes. Tumor cell lysis and cytokines secretion by lymphocytes were analyzed by LDH quantification and ELISA, respectively. Orthotopic 4T1 xenografts in syngeneic mice were used for dissecting the effect of aptamer/mAbs combination on tumor growth, metastasis and lymphocytes infiltration. Ex vivo analyses through immunohistochemistry, RT-qPCR and immunoblotting were performed. Results: We show that the PDGFRβ aptamer potentiates the anti-proliferative activity of anti-PD-L1 mAbs on both human and murine TNBC cells, according to its human/mouse cross-reactivity. Further, by binding to activated human and mouse lymphocytes, the aptamer enhances the anti-PD-L1 mAbs-induced cytotoxicity of lymphocytes against tumor cells. Importantly, the aptamer heightens the antibody efficacy in inhibiting tumor growth and lung metastases in a syngeneic mouse model by acting on both TME and cancer cells. Conclusion: Co-treatment of PDGFRβ aptamer with anti-PD-L1 mAbs is a viable strategy, thus providing for the first an evidence of the efficacy of PDGFRβ/PD-L1 co-targeting combination therapy in TNBC.
Clinical Significance of Circulating Exosomal PD-L1 and Soluble PD-L1 in Nasal-type NK/T-cell Lymphoma Patients Receiving VIPD Containing Chemotherapy
Authors: Li Jiwei , Wei Ping , Guo Ye , Shi Di , Yu Bao-Hua , Su Yi-Fan , Li Xiao-Qiu , Zhou Xiao-Yan 
Published: August 2020

Abstract
Background: Several studies showed that circulating exosomal PD-L1 was associated with immunosuppression and prognosis in cancer patients. However, its prognostic value in extranodal NK/T cell lymphoma (ENKTCL) was poorly understood.Methods: We retrospectively evaluated the prognostic value of pretreatment circulating PD-L1+ exosomes and soluble PD-L1 in the plasma of ENKTCL patients treated with VIPD-containing chemotherapy. Results: A total of 107 ENKTCL patients, including 101 early stage and 6 advanced stage patients were enrolled in our study. Most patients were middle-aged and young male adults, with a male to female ratio of approximately 3.7:1. The 5-year progression-free survival (PFS) and 5-year overall survival (OS) rates were 65.2% and 85.7% for the whole cohort, respectively. For early-stage patients, the L/P-VIPD group had better 5-year PFS than the VIPD group (73.6% vs. 53.7%, P=0.031). Compared with the healthy individuals (n=16), the patients with ENKTCL exhibited significantly elevated exoPD-L1 and sPD-L1 levels in the blood. Five-year PFS and OS rates were significantly lower in the high exoPD-L1 and sPD-L1 group than in the low exoPD-L1 and sPD-L1group. However, no correlation was found between circulating exoPD-L1 and sPD-L1 levels (P=0.12, r=0.45).Conclusions: Our results demonstrated that VIPD-containing chemotherapy combined with radiotherapy was a promising regimen in ENKTCL patients. Circulating exoPD-L1 and sPD-L1 levels were significantly elevated in ENKTCL and might be potential biomarkers for predicting the survival outcomes of ENKTCL patients.
Histone Tail Analysis Reveals H3K36me2 And H4K16ac As Epigenetic Signatures of Diffuse Intrinsic Pontine Glioma
Authors: An Shejuan , Camarillo Jeannie , Huang Tina , Li Daphne , Morris Juliette , Zoltek Madeline , Qi Jin , Behbahani Mandana , Kelleher Neil , Nazarian Javad , Thomas Paul , Saratsis Amanda Muhs 
Published: August 2020

Abstract
Background: Diffuse intrinsic pontine glioma (DIPG) is an aggressive pediatric brainstem tumor. Most DIPGs harbor a histone H3 mutation, which alters histone post-translational modification (PTM) states and transcription. Here, we employed quantitative proteomic analysis to elucidate the impact of H3.3K27M mutation, as well as radiation and bromodomain inhibition (BRDi) with JQ1, on DIPG PTM profiles.Methods: We performed targeted mass spectroscopy on H3.3K27M mutant and wild-type tissues (n=12) and cell lines (n=7).Results: We found 29.2% and 26.4% of total H3.3K27 peptides were H3.3K27M in mutant DIPG tumor cell lines and tissue specimens, respectively. Significant differences in distinct PTMs were observed in H3.3K27M specimens, including at H3K27, H3K36, and H4K16 amino acid residues. In addition, H3.3K27me1 and H4K16ac were the most significantly distinct modifications in H3.3K27M mutant tumors relative to wild-type. Further, H3.3K36me2 was the most abundant modification co-occurring on the H3.3K27M mutant peptide in DIPG tissue, while H4K16ac was the most acetylated residue. Radiation treatment caused changes in PTM abundance in vitro, including increased H3K9me3. BRDi with JQ1 resulted in increased mono- and di-methylation of H3.1K27, H3.3K27, H3.3K36 and H4K20 in vitro. Conclusion: Taken together, our findings provide insight into the effects of the H3K27M mutation on Histone modification states and response to treatment, and suggest H3K36me2 and H4K16ac in DIPG may represent unique tumor epigenetic signatures for targeted therapy.