bluuebunny/crossref_metadata_2025_split huggingface dataset:
Randomized Trial of Silver Nitrate with Sodium Fluoride for Caries Arrest
Authors: Gao S.S. , Duangthip D. , Wong M.C.M. , Lo E.C.M. , Chu C.H. 
Published: February 2019

Objectives: The aim of this noninferiority double-blind randomized clinical trial was to compare the effectiveness of the topical semiannual application of a 25% silver nitrate (AgNO3) solution followed by a 5% sodium fluoride (NaF) varnish with that of a 38% silver diamine fluoride (SDF) solution in arresting caries among preschool children. Methods: Healthy 3-y-old children with active dentine carious lesions were randomly allocated to 2 groups via computer-generated random numbers. Lesions in group A received applications of a 25% AgNO3 solution followed by a 5% NaF varnish semiannually (every 6 mo). Lesions in group B received semiannual applications of a 38% SDF solution followed by a placebo varnish. A trained examiner recorded the status of caries and oral hygiene at baseline and during follow-up examinations. The examiner, children, and their caretakers were blinded to the intervention allocation. This study adopted an intention-to-treat analysis. A noninferiority test was conducted for the data analysis. Group A’s noninferiority was accepted if the lower limit of the 95% CI for the difference in the mean number of arrested surfaces was >−0.5. Results: A total of 1,070 children were recruited at baseline, with 535 children in each group. After 18 mo, the mean ± SD number of arrested surfaces was 3.3 ± 3.4 in group A (n = 484) and 3.2 ± 3.5 in group B (n = 476; P = 0.664). The difference in the mean number of arrested surfaces between the groups was 0.092 (95% CI, −0.322 to 0.505). Apart from black staining on the arrested lesions, no other significant side effect was observed. Conclusion: A semiannual application of 25% AgNO3 followed by 5% NaF is no worse than a 38% SDF in arresting dentine caries among preschool children over 18 mo. The Hong Kong Research Grants Council (GRF 17107315) funded this trial, which was registered at ClinicalTrials.gov (NCT02019160). Knowledge Transfer Statement: This randomized clinical trial found that silver nitrate solution followed by sodium fluoride varnish is effective in arresting dentine caries among preschool children. As silver nitrate followed by sodium fluoride is a noninvasive and simple protocol, it can be an alternative strategy to manage dental caries among young children, especially in countries where silver diamine fluoride is not available.
Coexisting nanoscale phases of K-illite, NH4,K-illite and NH4-illite-smectite: an organic nitrogen contribution in the hydrothermal system of Harghita Bãi, East Carpathians, Romania
Authors: Bobos Iuliu 
Published: February 2019

AbstractNitrogen influx was identified in the Harghita Bãi area, where the mechanism of NH4+-fixation in illitic clays is relevant for the N-input budget estimation. The nanotextural features of K-illite (K-I), NH4,K-I and NH4-illite-smectite (NH4-I-S) mixed layers observed in argillic-altered andesitic rocks from the hydrothermal area of Harghita Bãi (East Carpathians) were studied by X-ray diffraction, infrared spectroscopy and transmission and analytical electron microscopy (TEM-AEM). The texture of undisturbed argillic-altered andesite rocks exhibits chaotic intergrowths of randomly oriented and curved illitic packets with abundant pore spaces and high porosity between packets. The TEM images of K-I and NH4,K-I intergrowths show subparallel packets with clear contacts, exhibiting a diffuse contrast across layers. The thicknesses of K-I and NH4,K-I packets range from 150 to 500 Å, and 1Md and 1M polytypes were identified by selected area electron diffraction patterns. Crystal chemistry of K-I, NH4,K-I and NH4-I-S was carried out by AEM. A third interlayer cation Na+ beside K+ was detected in several NH4,K-I packets. The NH4,Na,K-I packets interleaved with NH4,K-I or NH4-I-S (12% smectite layers) packets were also identified by TEM. The thicknesses of NH4,Na,K-I packets range from 300 to 1200 Å, with abundant lenses and lenticular layer separation along the boundaries between them. The 1Md polytype dominates the NH4,Na,K-I packets. Straight and parallel packets, continuous 00l layers and collapsed swelling layers at the boundary of individual NH4-I (5% smectite layers) packets with thicknesses ranging from 20 to 95 Å were observed. The nanotextural observations indicate direct crystallization of NH4-I crystals within a NH4-I-S series from a pore fluid, where NH4-I packets occupy void spaces previously occupied by fluids.
Characterization and treatment of congenital thrombotic thrombocytopenic purpura
Authors: Alwan Ferras , Vendramin Chiara , Liesner Ri , Clark Amanda , Lester William , Dutt Tina , Thomas William , Gooding Richard , Biss Tina , Watson H. G. , Cooper Nichola , Rayment Rachel , Cranfield Tanya , van Veen Joost J. , Hill Quentin A. , Davis Sarah , Motwani Jayashree , Bhatnagar Neha , Priddee Nicole , David Marianna , Crowley Maeve P. , Alamelu Jayanthi , Lyall Hamish , Westwood John-Paul , Thomas Mari , Scully Marie 
Published: February 2019

Abstract
Congenital thrombotic thrombocytopenic purpura (cTTP) is an ultra-rare thrombomicroangiopathy caused by an inherited deficiency of a disintegrin and metalloproteinase with a thrombospondin type 1 motif, member 13 (ADAMTS13). There are limited data on genotype-phenotype correlation; there is no consensus on treatment. We reviewed the largest cohort of cTTP cases, diagnosed in the United Kingdom, over the past 15 years. Seventy-three cases of cTTP were diagnosed, confirmed by genetic analysis. Ninety-three percent were alive at the time of review. Thirty-six percent had homozygous mutations; 64% had compound heterozygous mutations. Two presentation peaks were seen: childhood (median diagnosis age, 3.5 years) and adulthood, typically related to pregnancy (median diagnosis age, 31 years). Genetic mutations differed by age of onset with prespacer mutations more likely to be associated with childhood onset (P = .0011). Sixty-nine percent of adult presentations were associated with pregnancy. Fresh-frozen plasma (FFP) and intermediate purity factor VIII concentrate were used as treatment. Eighty-eight percent of patients with normal blood counts, but with headaches, lethargy, or abdominal pain, reported symptom resolution with prophylactic therapy. The most common currently used regimen of 3-weekly FFP proved insufficient for 70% of patients and weekly or fortnightly infusions were required. Stroke incidence was significantly reduced in patients receiving prophylactic therapy (2% vs 17%; P = .04). Long-term, there is a risk of end-organ damage, seen in 75% of patients with late diagnosis of cTTP. In conclusion, prespacer mutations are associated with earlier development of cTTP symptoms. Prophylactic ADAMTS13 replacement decreases the risk of end-organ damage such as ischemic stroke and resolved previously unrecognized symptoms in patients with nonovert disease.
PD-L1 and tumor-associated macrophages in de novo DLBCL
Authors: McCord Ronald , Bolen Christopher R. , Koeppen Hartmut , Kadel Edward E. , Oestergaard Mikkel Z. , Nielsen Tina , Sehn Laurie H. , Venstrom Jeffrey M. 
Published: February 2019

AbstractProgrammed death-ligand 1 (PD-L1) and its receptor, programmed cell death-1 (PD-1), are important negative regulators of immune cell activation. Therapeutically targeting PD-1/PD-L1 in diffuse large B-cell lymphoma (DLBCL) patients with a single agent has limited activity, meriting a deeper understanding of this complex biology and of available PD-L1 clinical assays. In this study, we leveraged 2 large de novo DLBCL phase 3 trials (GOYA and MAIN) to better understand the biologic and clinical relevance of PD-L1 in de novo DLBCL. PD-L1 was expressed on myeloid cells in 85% to 95% of DLBCL patients (depending on staining procedure), compared with 10% on tumor cells, and correlated with macrophage gene expression. PD-L1 did not identify high-risk patients in de novo DLBCL; it correlated with STAT3, macrophage gene expression, and improved outcomes among a subset of patients. These results may help identify immunologically distinct DLBCL subsets relevant for checkpoint blockade. GOYA and MAIN trials were registered at www.clinicaltrials.gov as #NCT01287741 and #NCT00486759, respectively.
RETRACTED ARTICLE: Exosomes from glioma cells induce a
tumor-like phenotype in mesenchymal stem cells by activating glycolysis
Authors: Ma Zhanjun , Cui Xue , Lu Li , Chen Guohu , Yang Yang , Hu Yan , Lu Yubao , Cao Zhangqi , Wang Yan , Wang Xuexi 
Published: February 2019

Abstract
Background
Exosomes are nanoscale membrane vesicles secreted by both normal and
cancer cells, and cancer cell-derived exosomes play an important role in the
cross-talk between cancer cells and other cellular components in the tumor
microenvironment. Mesenchymal stem cells (MSCs) have tropism for tumors and have
been used as tumor-tropic vectors for tumor therapy; however, the safety of such
therapeutic use of MSCs is unknown. In this study, we investigated the role of
glioma cell-derived exosomes in the tumor-like phenotype transformation of human
bone marrow mesenchymal stem cells (hBMSCs) and explored the underlying molecular
mechanisms.

Methods
The effect of exosomes from U251 glioma cells on the growth of
hBMSCs was evaluated with the CCK-8 assay, KI67 staining, and a cell cycle
distribution assessment. The migration and invasion of hBMSCs were evaluated with
a Transwell assay. A proteomics and bioinformatics approach, together with Western
blotting and reverse transcriptase-polymerase chain reaction, was used to
investigate the effect of U251 cell-derived exosomes on the proteome of
hBMSCs.

Results
U251 cell-derived exosomes induced a tumor-like phenotype in hBMSCs
by enhancing their proliferation, migration, and invasion and altering the
production of proteins involved in the regulation of the cell cycle. Moreover,
U251 cell-derived exosomes promoted the production of the metastasis-related
proteins MMP-2 and MMP-9, glioma marker GFAP, and CSC markers (CD133 and Nestin).
The ten differentially expressed proteins identified participated in several
biological processes and exhibited various molecular functions, mainly related to
the inactivation of glycolysis. Western blotting showed that U251 cell-derived
exosomes upregulated the levels of Glut-1, HK-2, and PKM-2, leading to the
induction of glucose consumption and generation of lactate and ATP. Treatment with
2-deoxy-d-glucose significantly reversed
these effects of U251 cell-derived exosomes on hBMSCs.

Conclusions
Our data demonstrate that glioma cell-derived exosomes activate
glycolysis in hBMSCs, resulting in their tumor-like phenotype transformation. This
suggests that interfering with the interaction between exosomes and hBMSCs in the
tumor microenvironment has potential as a therapeutic approach for glioma.

Graphical abstract
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Application of Circulating Cell-Free Tumor DNA Profiles for Therapeutic Monitoring and Outcome Prediction in Genetically Heterogeneous Metastatic Melanoma
Authors: Váraljai Renáta , Wistuba-Hamprecht Kilian , Seremet Teofila , Diaz Joey Mark S. , Nsengimana Jérémie , Sucker Antje , Griewank Klaus , Placke Jan-Malte , Horn Peter A. , von Neuhoff Nils , Shannan Batool , Chauvistré Heike , Vogel Felix C. E. , Horn Susanne , Becker Jürgen C. , Newton-Bishop Julia , Stang Andreas , Neyns Bart , Weide Benjamin , Schadendorf Dirk , Roesch Alexander 
Published: February 2019

PURPOSECirculating cell-free tumor DNA (ctDNA) reflects the heterogeneous spectrum of tumor-specific mutations, especially in systemic disease. We validated plasma-based assays that allow the dynamic quantitative detection of ctDNA as a prognostic biomarker for tumor load and prediction of therapy response in melanoma.MATERIALS and METHODSWe analyzed plasma-derived ctDNA from a large training cohort (n = 96) of patients with advanced-stage melanoma, with assays for the BRAFV600Eand NRASQ61driver mutations as well as TERTC250Tand TERTC228Tpromoter mutations. An independent patient cohort (n = 35) was used to validate the utility of ctDNA monitoring under mitogen-activated protein kinase–targeted or immune checkpoint therapies.RESULTSElevated plasma ctDNA level at baseline was an independent prognostic factor of disease progression when compared with serum S100 and lactate dehydrogenase levels in multivariable analyses (hazard ratio [HR], 7.43; 95% CI, 1.01 to 55.19; P = .05). The change in ctDNA levels during therapy correlated with treatment response, where increasing ctDNA was predictive for shorter progression-free survival (eg, for BRAFV600EctDNA, HR, 3.70; 95% CI, 1.86 to 7.34; P < .001). Increasing ctDNA levels predicted disease progression significantly earlier than did routine radiologic scans ( P < .05), with a mean lead time of 3.5 months. NRAS-mutant ctDNA was detected in a significant proportion of patients with BRAF-mutant tumors under therapy, but unexpectedly also at baseline. In vitro sensitivity studies suggested that this represents higher-than-expected intratumoral heterogeneity. The detection of NRASQ61ctDNA in baseline samples of patients with BRAFV600Emutation who were treated with mitogen-activated protein kinase inhibitors significantly correlated with shorter progression-free survival (HR, 3.18; 95% CI, 1.31 to 7.68; P = .03) and shorter overall survival (HR, 4.08; 95% CI, 1.57 to 10.58; P = .01).CONCLUSIONOur results show the potential role of ctDNA measurement as a sensitive monitoring and prediction tool for the early assessment of disease progression and therapeutic response in patients with metastatic melanoma.
Rho-of-plant activated root hair formation requires Arabidopsis YIP4a/b gene function
Authors: Gendre Delphine , Baral Anirban , Dang Xie , Esnay Nicolas , Boutté Yohann , Stanislas Thomas , Vain Thomas , Claverol Stéphane , Gustavsson Anna , Lin Deshu , Grebe Markus , Bhalerao Rishikesh P. 
Published: February 2019

ABSTRACT
Root hairs are protrusions from root epidermal cells with crucial roles in plant soil interactions. Although much is known about patterning, polarity and tip growth of root hairs, contributions of membrane trafficking to hair initiation remain poorly understood. Here, we demonstrate that the trans-Golgi network-localized YPT-INTERACTING PROTEIN 4a and YPT-INTERACTING PROTEIN 4b (YIP4a/b) contribute to activation and plasma membrane accumulation of Rho-of-plant (ROP) small GTPases during hair initiation, identifying YIP4a/b as central trafficking components in ROP-dependent root hair formation.
Non-apoptotic function of Drosophila caspase activation in epithelial thorax closure and wound healing
Authors: Fujisawa Yuya , Kosakamoto Hina , Chihara Takahiro , Miura Masayuki 
Published: February 2019

ABSTRACT
Non-apoptotic caspase activation involves multiple cellular events. However, the link between visible non-apoptotic caspase activation and its function in living organisms has not yet been revealed. Here, we visualized sub-lethal activation of apoptotic signaling with the combination of a sensitive indicator for caspase 3 activation and in vivo live-imaging analysis of Drosophila. During thorax closure in pupal development, caspase 3 activation was specifically observed at the leading edge cells, with no signs of apoptosis. Inhibition of caspase activation led to an increase in thorax closing speed, which suggests a role of non-apoptotic caspase activity in cell motility. Importantly, sub-lethal activation of caspase 3 was also observed during wound closure at the fusion sites at which thorax closure had previously taken place. Further genetic analysis revealed that the activation of the initiator caspase Dronc is coupled with the generation of reactive oxygen species. The activation of Dronc also regulates myosin levels and delays wound healing. Our findings suggest a possible function for non-apoptotic caspase activation in the fine-tuning of cell migratory behavior during epithelial closure.
Lmx1a drives Cux2 expression in the cortical hem through activation of a conserved intronic enhancer
Authors: Fregoso Santiago P. , Dwyer Brett E. , Franco Santos J. 
Published: February 2019

ABSTRACT
During neocortical development, neurons are produced by a diverse pool of neural progenitors. A subset of progenitors express the Cux2 gene and are fate restricted to produce certain neuronal subtypes; however, the upstream pathways that specify these progenitor fates remain unknown. To uncover the transcriptional networks that regulate Cux2 expression in the forebrain, we characterized a conserved Cux2 enhancer that recapitulates Cux2 expression specifically in the cortical hem. Using a bioinformatic approach, we identified putative transcription factor (TF)-binding sites for cortical hem-patterning TFs. We found that the homeobox TF Lmx1a can activate the Cux2 enhancer in vitro. Furthermore, we showed that Lmx1a-binding sites were required for enhancer activity in the cortical hem in vivo. Mis-expression of Lmx1a in hippocampal progenitors caused an increase in Cux2 enhancer activity outside the cortical hem. Finally, we compared several human enhancers with cortical hem-restricted activity and found that recurrent Lmx1a-binding sites are a top shared feature. Uncovering the network of TFs involved in regulating Cux2 expression will increase our understanding of the mechanisms pivotal in establishing Cux2 lineage fates in the developing forebrain.
VERNALIZATION1 controls developmental responses of winter wheat under high ambient temperatures
Authors: Dixon Laura E. , Karsai Ildiko , Kiss Tibor , Adamski Nikolai M. , Liu Zhenshan , Ding Yiliang , Allard Vincent , Boden Scott A. , Griffiths Simon 
Published: February 2019

ABSTRACT
Low temperatures are required to regulate the transition from vegetative to reproductive growth via a pathway called vernalization. In wheat, vernalization predominantly involves the cold upregulation of the floral activator VERNALIZATION1 (VRN1). Here, we have used an extreme vernalization response, identified through studying ambient temperature responses, to reveal the complexity of temperature inputs into VRN-A1, with allelic inter-copy variation at a gene expansion of VRN-A1 modulating these effects. We find that the repressors of the reproductive transition, VERNALIZATION2 (VRN2) and ODDSOC2, are re-activated when plants experience high temperatures during and after vernalization. In addition, this re-activation is regulated by photoperiod for VRN2 but was independent of photoperiod for ODDSOC2. We also find this warm temperature interruption affects flowering time and floret number and is stage specific. This research highlights the important balance between floral activators and repressors in coordinating the response of a plant to temperature, and that the absence of warmth is essential for the completion of vernalization. This knowledge can be used to develop agricultural germplasm with more predictable vernalization responses that will be more resilient to variable growth temperatures.
Aerobic Exercise Performance and Muscle Strength in Statin Users—The LIFESTAT Study
Authors: MORVILLE THOMAS , DOHLMANN TINE LOVSØ , KUHLMAN ANJA BIRK , SAHL RONNI EG , KRIEGBAUM MARGIT , LARSEN STEEN , DELA FLEMMING , HELGE JØRN WULFF 
Published: February 2019

ABSTRACT

Introduction
Statins are widely used in both primary and secondary prevention of cardiovascular disease. The treatment increases the risk of muscle pain (myalgia) which can affect muscle function and levels of physical activity. We investigated whether statin-associated myalgia is coupled to impaired aerobic exercise performance including fat oxidation as well as impaired muscle strength.

Methods
A population-based survey (6000 people) was performed to assess the prevalence of statin-associated myalgia in the Danish population. In addition, 64 statin users in primary prevention with myalgia (M; n = 25; 61 ± 1 yr) or without myalgia (NM; n = 37; 63 ± 1 yr) as well as a control group not taking statins (C; n = 20; 60 ± 2 yr) were enrolled in a cross-sectional study where they performed aerobic exercise and muscle strength tests.

Results
The response rate for the survey was 51% and data showed a prevalence of statin-associated myalgia in 19% of responders using statins. The experimental study showed no difference between the groups in aerobic capacity (C, 29 ± 1 mL O2·min−1·kg−1; M, 27 ± 1 mL O2·min−1·kg−1; NM, 28 ± 1 mL O2·min−1·kg−1) or maximal fat oxidation (C, 247 ± 26 mg·min−1; M, 295 ± 24 mg·min−1; NM, 279 ± 17 mg·min−1). Measurements of strength were similar in all three groups including rate of force development (C, 795 ± 56 N·m·s−1; M, 930 ± 93 N·m·s−1; NM, 971 ± 57 N·m·s−1) and leg extension power (C: 2.6 ± 0.2; M: 2.3 ± 0.1; NM: 2.4 ± 0.1 W·kg−1). All results are mean ± SEM.

Conclusion
Statin users in primary prevention experiencing myalgia do not have impaired aerobic exercise performance or muscle strength compared to nonmyalgic statin users or control subjects.
Does the Middle Conform or Compete? Quality Thresholds Predict the Locus of Innovation
Authors: Vashevko Anthony 
Published: February 2019

Where does innovation come from? This research models producer incentives to innovate with a focus on the role of audiences in constructing quality thresholds within markets. Market audiences create mechanisms for identifying the highest-quality producers in a market. I highlight a key distinction between fixed quality thresholds (such as accreditations) and quality thresholds that respond to producer quality (such as rankings or best-of-breed awards). Producers evaluate how the inherently risky nature of innovation interacts with these thresholds. The model predicts conditions under which innovation emerges from the best producers in a market, from producers near the threshold in a market, from both, or from nowhere. Such predictions generalize and simplify several existing organizational theories of innovation. The online appendix is available at https://doi.org/10.1287/orsc.2018.1240 .
Construction and stability of type I blowup solutions for non-variational semilinear parabolic systems
Authors: Ghoul Tej-Eddine , Nguyen Van Tien , Zaag Hatem 
Published: February 2019

AbstractIn this note, we consider the semilinear heat system\partial_{t}u=\Delta u+f(v),\quad\partial_{t}v=\mu\Delta v+g(u),\quad\mu>0,where the nonlinearity has no gradient structure taking of the particular formf(v)=v\lvert v\rvert^{p-1}\quad\text{and}\quad g(u)=u\lvert u\rvert^{q-1}\quad%
\text{with }p,q>1,orf(v)=e^{pv}\quad\text{and}\quad g(u)=e^{qu}\quad\text{with }p,q>0.We exhibit type I blowup solutions for this system and give a precise description of its blowup profiles. The method relies on a two-step procedure: the reduction of the problem to a finite-dimensional one via a spectral analysis, and then solving the finite-dimensional problem by a classical topological argument based on index theory. As a consequence of our technique, the constructed solutions are stable under a small perturbation of initial data. The results and the main arguments presented in this note can be found in our papers
[T.-E. Ghoul, V. T. Nguyen and H. Zaag,
Construction and stability of blowup solutions for a non-variational semilinear parabolic system,
Ann. Inst. H. Poincaré Anal. Non Linéaire 35 2018, 6, 1577–1630] and
[M. A. Herrero and J. J. L. Velázquez,
Generic behaviour of one-dimensional blow up patterns,
Ann. Sc. Norm. Super. Pisa Cl. Sci. (4) 19 1992, 3, 381–450].