bluuebunny/crossref_metadata_2025_split huggingface dataset:
Age-Related Changes and Effects of Bisphosphonates on Bone Turnover and Disease Progression in Fibrous Dysplasia of Bone
Authors: Florenzano Pablo , Pan Kristen S , Brown Sydney M , Paul Scott M , Kushner Harvey , Guthrie Lori C , de Castro Luis Fernandez , Collins Michael T , Boyce Alison M 
Published: January 2019

ABSTRACT

Fibrous dysplasia (FD) is a mosaic disease in which bone is replaced with fibro-osseous tissue. Lesions expand during childhood, reaching final burden by age 15 years. In vitro data suggest that disease activity decreases in adulthood; however, there is no clinical data to support this concept. Bone turnover markers (BTMs) have been used as markers of disease activity in FD; however, the natural history of BTM changes, the effects of antiresorptive treatment, and their association to clinical outcomes have not been described. The goals of this study are to describe 1) the natural history of FD disease activity and its association with pain; 2) the impact of bisphosphonates on the natural history of BTMs; and 3) the effect of bisphosphonates on progression of FD burden during childhood. Disease burden scores and alkaline phosphatase, osteocalcin, NTx, FGF23, and RANKL levels from 178 subjects in an FD/MAS natural history study were reviewed, including 73 subjects treated with bisphosphonates. BTMs, RANKL, and FGF23 demonstrated a sustained reduction with age. Bisphosphonate treatment did not significantly impact this age-dependent decrease in BTMs. Pain was more prevalent and severe in adults compared with children and was not associated with BTMs. In children, the progression of disease burden was not affected by bisphosphonates. In conclusion, FD is associated with an age-dependent decline in bone turnover and other markers of disease activity. Pain, in contrast, is more frequent and severe in adults with FD and is not related to bone turnover. Bisphosphonate treatment does not significantly impact the age-dependent decrease in bone turnover, nor does it prevent the progression of FD disease burden in children. These findings, in association with the established adverse effects of antiresorptives, should be considered when evaluating use and response to bisphosphonates in patients being treated for FD and in any study using BTMs as surrogate endpoints. © 2019 American Society for Bone and Mineral Research.
ZCCHC9 promotes proliferation and invasion of lung cancer through regulating the JNK pathway
Authors: Shi Xiuying , Jiang Biying , Liu Haifeng , Fan Chuifeng 
Published: January 2019

AbstractZCCHC9 is a type of CCHC type zinc‐finger containing protein which was found to be expressed in some tissues including brain and testicles in mice. Expression and function of ZCCHC9 in human tissues including cancer was largely unknown. In this study, we investigated the expression and function of ZCCHC9 in human non‐small cell lung cancer (NSCLC) and the related molecular mechanism. Immunochemistrical standing showed that ZCCHC9 was mainly located in the nucleus in bronchial epithelial cells and epithelial cells of submucosal glands (58.3% [14/24]). But in NSCLC cells ZCCHC9 was mainly located in the cytoplasm and the positive rate was 54.5% (60/110). Ectopic cytoplasmic expression of ZCCHC9 in cancer tissues was significantly associated with advanced TNM stages (III+IV), lymph node metastasis, and poor clinical outcome (P < 0.05). Overexpression of cytoplasmic ZCCHC9 using transfection of ZCCHC9 cDNA in A549 and NCI‐H1299 cells significantly upregulated the proliferation and invasion of these cancer cells in vitro (P < 0.05). Western blot study showed that overexpression of cytoplasmic ZCCHC9 significantly upregulated expression of p‐JNK, Cyclin D1, and MMP7 (P < 0.05). Next we used the inhibitor of JNK pathway to inhibit the activity of the JNK pathway and the results showed that co‐addition of SP600125 significantly abolished the function of ZCCHC9 to promote the proliferation and invasion of cancer cells. These results indicate that cytoplasmic ZCCHC9 could promote the proliferation and invasion of NSCLC through the JNK pathway and may be a promising cancer maker.
Long noncoding RNA MEG3 regulates rheumatoid arthritis by targeting NLRC5
Authors: Liu Ya‐ru , Yang Lei , Xu Qing‐qing , Lu Xin‐Yi , Ma Tao‐Tao , Huang Cheng , Li Jun 
Published: January 2019

AbstractRheumatoid arthritis (RA) is one of the chronic systemic autoimmune diseases that cardinally affect the joints. Many people all over the world suffer from the disease. Fibroblast‐like synoviocytes (FLSs) play a significant role in the occurrence and development of RA. The long noncoding RNA maternally expressed gene 3 (MEG3) is an imprinted gene, which participates in various cancers as a tumor suppressor. Previous studies have shown that nucleotide oligomerization domain (NOD)‐like receptors 5 (NLRC5) plays a key role in inflammatory and autoimmune diseases. Nonetheless, we know very little about the biofunctionality of MEG3 during the development of RA. In this paper, we used complete Freund's adjuvant (CFA)‐induced rats as RA animal models. The level of MEG3 significantly reduced in CFA‐induced synovial tissues and FLSs, whereas the NLRC5 levels were increased. Enforced expression of MEG3 may be responsible for the decreased level of NLRC5 and inflammatory cytokine level. The results of methylation‐specific PCR suggested that the MEG3 gene promoter was significantly methylated in CFA‐induced synovial tissues and FLSs. More important, hypermethylation of MEG3 promoter could be inhibited by 5‐aza‐2‐deoxycytidine (5‐azadC; methylation inhibitor). Besides, the expression of NLRC5 significantly decreased followed by 5‐azadc. Furthermore, DNA methyltransferases 1 (DNMT1) increased in CFA‐induced synovial tissues and cells. These results indicated that MEG3 regulates RA by targeting NLRC5 potentially.
microRNA‐505 negatively regulates HMGB1 to suppress cell proliferation in renal cell carcinoma
Authors: Zhong Bing , Qin Zhiqiang , Zhou Hui , Yang Fengming , Wei Ke , Jiang Xi , Jia Ruipeng 
Published: January 2019

AbstractmicroRNAs have been recognized to regulate a wide range of biology of renal cell carcinoma (RCC). Although miR‐505 has been reported to play as a suppressor in several human tumors, the physiological function of miR‐505 in RCC still remain unknown. Therefore, the role of miR‐505 and relevant regulatory mechanisms were investigated in RCC in this study. Quantitative real‐time polymerase chain reaction was conducted to detect the expression of miR‐505 and high mobility group box 1 (HMGB1) in both RCC tissues and cell lines. Immunohistochemical staining was used to assess the correlation between HMGB1 expression and PCNA expression in RCC tissues. Subsequently, the effects of miR‐505 on proliferation were determined in vitro using cell counting kit‐8 proliferation assays and 5‐ethynyl‐2′‐deoxyuridine incorporation. The molecular mechanism underlying the relevance between miR‐505 and HMGB1 was confirmed by luciferase assay. Xenograft tumor formation was used to reflect the proliferative capacity of miR‐505 in vivo experiments. Overall, a relatively lower miR‐505 and higher HMGB1 expression in RCC specimens and cell lines were found. HMGB1 was verified as a direct target of miR‐505 by luciferase assay. In vitro, overexpression of miR‐505 negatively regulates HMGB1 to suppress the proliferation in Caki‐1; meanwhile, knock‐down of miR‐505 negatively regulates HMGB1 to promote the proliferation in 769P. In addition, in vivo overexpression of miR‐505 could inhibit tumor cell proliferation in RCC by xenograft tumor formation. Therefore, miR‐505, as a tumor suppressor, negatively regulated HMGB1 to suppress the proliferation in RCC, and might serve as a novel therapeutic target for RCC clinical treatment.
SNHG20: A vital lncRNA in multiple human cancers
Authors: Zhao Wei , Ma Xiaozhou , Liu Lina , Chen Qingyu , Liu Zihao , Zhang Zheng , Ma Shiqing , Wang Zhonghou , Li Hongfa , Wang Zuomin , Wu Jie 
Published: January 2019

AbstractLong noncoding RNAs (lncRNAs) act as an initial factor and promoter in different tumors as a kind of ncRNAs. The length of them is >200 nucleotides opposite small ncRNAs. Increasing researches have proved that dysregulation lncRNA has been implicated in tumorigenesis. Small nucleolar RNA host gene 20 (SNHG20), a member of lncRNAs, expresses frequently in cancer types, such as hepatocellular carcinoma, ovarian cancer, colorectal cancer, and bladder cancer, contributing to cancer development and progression by transcriptional or posttranscriptional modifications. Not only does this review show the recent published literature concerning the biological functions but also demonstrates molecular mechanisms of SNHG20 among above multiple malignancies and others.
Cells under stress: The mechanical environment shapes inflammasome responses to danger signals
Authors: Joshi Hemant , Morley Sharon Celeste 
Published: January 2019

Abstract
Many intracellular signals, such as host danger-associated molecules and bacterial toxins during infection, elicit inflammasome activation. However, the mechanical environment in tissues may also influence the sensitivity of various inflammasomes to activation. The cellular mechanical environment is determined by the extracellular tissue stiffness, or its inverse, tissue compliance. Tissue stiffness is sensed by the intracellular cytoskeleton through a process termed mechanotransduction. Thus, extracellular compliance and the intracellular cytoskeleton may regulate the sensitivity of inflammasome activation. Control of proinflammatory signaling by tissue compliance may contribute to the pathogenesis of diseases such as ventilator-induced lung injury during bacterial pneumonia and tissue fibrosis in inflammatory disorders. The responsible signaling cascades in inflammasome activation pathways and mechanotransduction crosstalk are not yet fully understood. This rather different immunomodulatory perspective will be reviewed and open questions discussed here.
Targeting NKG2A to elucidate natural killer cell ontogenesis and to develop novel immune-therapeutic strategies in cancer therapy
Authors: Zaghi Elisa , Calvi Michela , Marcenaro Emanuela , Mavilio Domenico , Di Vito Clara 
Published: January 2019

Abstract
Natural Killer (NK) cells are innate immune cells with a primary role in the immune surveillance against non-self-cells. NK cell recognition of “self” relies on the surface expression on autologous cells of MHC class I (MHC-I) molecules. Either the absence or the down-modulation of MHC-I on target cells “license” NK cells to kill threatening tumor-transformed or virally infected cells. This phenomenon is controlled by a limited repertoire of activating and inhibitory NK receptors (aNKRs and iNKRs) that tunes NK cell activation and effector functions. Hence, the calibration of NK cell alloreactivity depends on the ability of iNKRs to bind MHC-I complex and these interactions are key in regulating both NK cell differentiation and effector functions. Indeed, the presence of iNKRs specific for self-MHC haplotypes (i) plays a role in the “licensing/education” process that controls the responsiveness of mature NK cells and prevents their activation against the “self” and (ii) is exploited by tumor cells to escape from NK cell cytotoxicity. Herein, we review our current knowledge on function and clinical application of NKG2A, a C-type lectin iNKR that binds specific haplotypes of human leukocyte antigens early during the NK cell maturation process, thus contributing to modulate the terminal maturation of NK cells as potent effectors against cancers cells. These NKG2A-mediated mechanisms are currently being exploited for developing promising immune-therapeutic strategies to improve the prognosis of solid and blood tumors and to ameliorate the clinical outcome of patients undergone allogeneic hematopoietic stem cell transplantation to treat high-risk hematologic malignancies.
Altered functional connectivity of the marginal division in Parkinson's disease with mild cognitive impairment: A pilot resting‐state fMRI study
Authors: Li Ming‐ge , Chen Yuan‐yuan , Chen Zhi‐ye , Feng Jie , Liu Meng‐yu , Lou Xin , Shu Si‐yun , Wang Zhen‐fu , Ma Lin 
Published: January 2019

BackgroundThe marginal division (MrD) is an important subcortical center involved in learning and memory. Mild cognitive impairment (MCI) is commonly seen in patients with Parkinson's disease (PD), but the neurobiological basis is yet to be elucidated.PurposeTo use resting‐state functional magnetic resonance imaging (rs‐fMRI) to explore the altered functional connectivity (FC) of the MrD in patients with PD‐MCI.Study TypeProspective pilot study.PopulationTwenty‐five patients with PD‐MCI; 25 PD patients and no cognitive impairment (PD‐NCI); and 25 healthy control (HC) participants.Sequence3.0 T GE Healthcare MRI scanner; three‐dimensional T1‐weighted fast spoiled gradient recalled echo (3D T1‐FSPGR); rs‐fMRI.AssessmentThe MrD was defined using manual delineation, which was the seed point to compute the FC to examine correlations between low‐frequency fMRI signal fluctuations in MrD and the whole brain.Statistical TestsBetween‐group comparisons of the rs‐fMRI data were computed using two‐sample t‐tests in a voxelwise manner after controlling for age and sex, to determine the brain regions that showed significant differences in FC with the bilateral MrDs. Correlation analyses were performed for FC values and cognitive abilities in patients with PD.ResultsIn the PD‐MCI group, compared with the PD‐NCI group, we observed lesser FC between the MrD bilaterally and right putamen, left insula, left cerebellum, and left thalamus; greater FC between the MrD bilaterally and left middle cingulate cortex, left middle frontal gyrus, left superior frontal gyrus, left supplementary motor area, and left middle/inferior occipital gyrus. Moreover, the strength of FC between the MrD and regions that showed differences between the PD‐MCI and PD‐NCI groups was significantly correlated with neuropsychological scores in patients with PD.Data ConclusionThe current study suggests that MrD dysfunction may contribute to MCI in PD. However, the mechanisms underlying this process require further investigation.Level of Evidence 1.Technical Efficacy Stage 2.J. Magn. Reson. Imaging 2019;50:183–192.
Periodontal ligament‐derived mesenchymal stem cells modulate neutrophil responses via paracrine mechanisms
Authors: Misawa Mônica Yuri Orita , Silvério Ruiz Karina Gonzales , Nociti Francisco Humberto , Albiero Mayra Laino , Saito Miki Taketomi , Nóbrega Stipp Rafael , Condino‐Neto Antônio , Holzhausen Marinella , Palombo Henrique , Villar Cristina Cunha 
Published: January 2019

AbstractBackgroundMesenchymal stem cells differentiate into distinct mesenchymal cell lineages and regulate the immune response. The aim of this study was to determine whether periodontal ligament‐derived mesenchymal stem cells (PDLSCs) have the ability to modulate neutrophil responses via paracrine mechanisms.MethodsCD105‐enriched PDLSCs were seeded for 24 h and challenged with Porphyromonas gingivalis total protein extract (PgPE) (0 or 2 ug/mL) for 3 h. Cells were then washed and further cultured for 18 h and the supernatants were collected and stored. Next, neutrophil‐differentiated human promyelocytic leukemia HL‐60 cells (HL60D) were treated with PDLSCs supernatants and HL‐60D activation and functional responses were determined.ResultsPgPE treatment induced higher secretion of inflammatory markers and chemokines by PDLSCs, including RANTES, eotaxin, interferon (IFN)‐γ‐ inducible protein 10 (IP‐10), monocyte chemoattractant protein‐1 (MCP‐1), IFN‐γ, interleukin (IL)‐6, IL‐8 and IL‐1ra (P < 0.05). HL‐60D recruitment rate was increased by 4.7 ± 1.09‐fold when exposed to PgPE‐treated PDLSCs supernatants. PgPE‐treated PDLSCs supernatants promoted a 1.78 ± 1.04‐fold increase in the production of intracellular reactive oxygen species (ROS) by PMA‐stimulated HL‐60D, whereas PgPE‐untreated PDLSCs supernatants led to a 16% reduction in intracellular ROS. In sharp contrast, neither PgPE‐untreated nor PgPE‐treated PDLSCs supernatants altered tumor necrosis factor (TNF)‐α and IL‐1β secretion by HL‐60D cells.ConclusionTogether, these findings suggest an important role of PDLSCs in the recognition of P. gingivalis, paracrine recruitment and activation of antimicrobial mechanisms in innate immune cells, without interfering in cytokine responses.
SNAr reactions of substituted pyridines with secondary amines in aqueous solution: Kinetic and reactivity indices in density functional theory
Authors: Mahdhaoui Faouzi , Zaier Rania , Dhahri Nejeh , Ayachi Sahbi , Boubaker Taoufik 
Published: January 2019

AbstractA kinetic study is reported for the reactions of 2‐methoxy‐3‐nitropyridine 1a and 2‐methoxy‐5‐nitropyridine 1b with three secondary amines 2a–c (morpholine, piperidine, and pyrrolidine) in aqueous solution at 20°C. The Brønsted‐type plots are linear with βnuc = 0.52 and 0.55 for pyridines 1a and 1b, respectively, indicating that the reaction proceeds through a SNAr mechanism in which the first step is the rate‐determining step. Additional theoretical calculations using the DFT/B3LYP method confirm that the C‐2 carbon being the most electrophilic center for the both pyridines 1a and 1b. The second‐order rate constants have been used to evaluate the electrophilicity parameters E of 1a and 1b according to the linear free energy relationship log k (20°C) = sN (N + E). The E parameters thus derived are compared with the electrophilic reactivities of a large variety of anisoles. The validity of these E values has been satisfactorily verified by comparison of calculated and experimental second‐order rate constants for the reactions of pyridines 1a and 1b with anion of ethyl benzylacetate.
Turbulent convection and high‐frequency internal wave details in 1‐m shallow waters
Authors: van Haren Hans 
Published: January 2019

AbstractVertically 0.042‐m‐spaced moored high‐resolution temperature sensors are used for detailed internal wave‐turbulence monitoring near Texel North Sea and Wadden Sea beaches on calm summer days. In the maximum 2‐m deep waters, irregular internal waves are observed supported by the density stratification during day‐times’ warming in early summer, outside the breaking zone of < 0.2 m surface wind waves. Internal‐wave–induced convective overturning near the surface and shear‐driven turbulence near the bottom are observed in addition to near‐bottom convective overturning due to heating from below. Small turbulent overturns have durations of 5–20 s, close to the surface wave period and about one third to one tenth of the shortest internal wave period. The largest turbulence dissipation rates are estimated to be of the same order of magnitude as found above deep‐ocean seamounts, whereas overturning scales are observed 100 times smaller. The turbulence inertial subrange is observed to link between the internal and surface wave spectral bands.
Construction of Antibacterial N‐Halamine Polymer Nanomaterials Capable of Bacterial Membrane Disruption for Efficient Anti‐Infective Wound Therapy
Authors: Gao Yangyang , Song Nan , Liu Wenxin , Dong Alideertu , Wang Yan‐Jie , Yang Ying‐Wei 
Published: January 2019

AbstractThe increasing occurrence of bacterial infection at the wound sites is a serious global problem, demanding the rapid development of new antibacterial materials for wound dressing to avoid the abuse of antibiotics and thereby antibiotic resistance. In this work, the authors first report on antibacterial N‐halamine polymer nanomaterials based on a strategic copolymerization of 3‐allyl‐5,5‐dimethylhydantoin (ADMH) and methyl methacrylate (MMA), which exhibits in vitro and in vivo antimicrobial efficacy against pathogenic bacteria including Staphylococcus aureus and Escherichia coli. Particularly, when a biological evaluation is run for wound therapy, the N‐halamine polymer nanomaterials exhibit a powerful antibacterial efficiency and wound healing ability after a series of histological examination of mouse wound. After the evaluation of biological and chemical surroundings, the proposed four‐stage mechanism suggests that, with unique antibacterial NCl bonds, the N‐halamine polymer nanomaterials can disrupt the bacterial membrane, as a result causing intracellular content leaked out and thereby cell death. Based on the synergistic action of antibacterial and wound therapy, the N‐halamine polymer nanomaterials are expected to be promising as wound dressing materials in medical healing and biomaterials.
Fractional powers of the Stokes operator with boundary conditions involving the pressure
Authors: Al Baba Hind 
Published: January 2019

AbstractSince the pioneer work of Leray [23] and Hopf [17], Stokes and Navier–Stokes problems have been often studied with Dirichlet boundary condition. Nevertheless, in the opinion of engineers and physicists such a condition is not always realistic in industrial and applied problems of origin. Thus arises naturally the need to carry out a mathematical analysis of these systems with different boundary conditions, which best represent the underlying fluid dynamic phenomenology. Based on the study of the complex and fractional powers of the Stokes operator with pressure boundary condition, we carry out a systematic treatment of the Stokes problem with the corresponding boundary conditions in ‐spaces.
The effect of activity identity fusion on negative consumer behavior
Authors: Hawkins Matthew A. 
Published: January 2019

AbstractNegative consumer behavior is an important research topic as it explores consumer behaviors that threaten a brand's image and financial stability. However, prior research offers conflicting findings on whether a strong consumer‐brand relationship hurts or protects a brand after a market disruption or a brand transgression. To provide clarity on this issue, this work argues that disrupting the consumer‐activity relationship motivates consumers to reaffirm and protect their identity, thereby leading to negative consumer behavior. The data reveal that, after a brand‐initiated market disruption, consumers with high activity identity fusion are more likely to spread negative word‐of‐mouth, boycott the brand, and avoid repurchasing the brand in the future. Moreover, the data suggest that high brand identity fusion protects the brand during market disruptions; therefore, prior conflicting results may be due to the fact that the consumer‐activity relationship was not accounted for. Theoretically, this work establishes that consumers' relationship with their consumption activities has significant impacts on consumer behavior. Brand managers and marketers are urged to develop strategies that focus on strengthening the consumer‐brand relationship and not the consumer‐activity relationship.
What motivates users to hashtag on social media?
Authors: Rauschnabel Philipp A. , Sheldon Pavica , Herzfeldt Erna 
Published: January 2019

AbstractHashtags (i.e., the # symbol) are gaining increased popularity among social media users. However, despite their intense use, little is known about their meanings. Only a few published studies have investigated fragmented aspects of hashtags and treated them as a functional means to structure content. In this study, we provide evidence that hashtags’ meanings go beyond structuring or spreading content and represent an integral element of contemporary communication via social media. In particular, this study presents a series of six empirical studies, following traditions in grounded theory and measurement theory research, to systematically assess motivations for using hashtags. The results uncover the existence of 10 different motivations for use (amusing, organizing, designing, conforming, trendgaging, bonding, inspiring, reaching, summarizing, and endorsing). In addition, we show how these motivations differ between platforms and also relate to different patterns of social media behavior. The results contribute to a better academic understanding of social media, provide managers with profound insights and can guide marketing tactics with hashtags.