bluuebunny/crossref_metadata_2025_split huggingface dataset:
Prognostic significance of mast cell and microvascular densities in malignant peripheral nerve sheath tumor with and without neurofibromatosis type 1
Authors: Vasconcelos Roberto André Torres de , Guimarães Coscarelli Pedro , Vieira Thyago Marsicano , Noguera Washington Silva , Rapozo Davy Carlos Mendes , Acioly Marcus André 
Published: February 2019

AbstractMalignant peripheral nerve sheath tumors (MPNSTs) are rare and aggressive soft tissue sarcomas with a significant susceptibility to metastasize early in their course. Pathogenesis is yet to be fully elucidated. Recently, the essential role of mast cells in the tumor onset of neurofibromatosis type 1 (NF1)‐associated neurofibromas and MPNSTs was confirmed in both experimental and human studies. In this study, we investigate mast cell density (MCD), microvascular density (MVD), and proliferation index (Ki‐67) in MPNST. A secondary aim was to correlate histological staining to clinical data and survival in patients with and without NF1. In total, 34 formalin‐fixed paraffin‐embedded MPNST tissues from 29 patients were eligible. MCD, MVD, and Ki‐67 labeling index (LI) were analyzed in all stained tissues by a computer‐based quantitative algorithm (Aperio ImageScope). In addition, chart review was performed for clinical data and survival analysis. Overall, MCD, MVD, and Ki‐67 LI were evenly distributed throughout tumor tissue. There was a negative correlation of NF1 status (affected, P = 0.037), tumor size (>10 cm, P = 0.023), and MVD in the tumor periphery (higher tercile, P = 0.002) to survival. Multivariate analysis confirmed the association of MVD in the tumor periphery (higher tercile, P = 0.019) with a decreased overall survival. Diverse mast cell and microvascular distributions suggest that angiogenesis in MPNST occurs independently. The role of mast cells in tumor progression is unclear and lacks prognostic value. Higher MVD has prognostic significance with possible therapeutic implications in MPNST.
Genome‐Scale CRISPR/Cas9 Screening Reveals Squalene Epoxidase as a Susceptibility Factor for Cytotoxicity of Malformin A1
Authors: Koizumi Yukio , Fukushima Jun , Kobayashi Yayoi , Kadowaki Ayumi , Natsui Miyuki , Yamaguchi Tomokazu , Imai Yumiko , Sugiyama Toshihiro , Kuba Keiji 
Published: February 2019

AbstractMalformin A1 (MA1) is a fungus‐produced cyclic pentapeptide. MA1 exhibits teratogenicity to plants, fibrinolysis‐enhancing activity, and cytotoxicity to mammalian cells. To clarify the cytotoxic mechanism of MA1, we screened for the genes involved in the cytotoxicity of MA1 in monocytoid U937 cells by using a CRISPR/Cas9‐based genome‐wide knockout library. Screening was performed by positive selection for cells that were resistant to MA1 treatment, and single guide RNAs (sgRNAs) integrated into MA1‐resistant cells were analyzed by high‐throughput sequencing. As a result of the evaluation of sgRNAs that were enriched in MA1‐resistant cells, SQLE, which encodes squalene epoxidase, was identified as a candidate gene. SQLE‐depleted U937 cells were viable in the presence of MA1, and squalene epoxidase inhibitor conferred MA1 resistance to wild‐type cells. These results indicate that squalene epoxidase is implicated in the cytotoxicity of MA1. This finding represents a new insight into applications of MA1 for treating ischemic diseases.
Higher‐Order Structures Based on Molecular Interactions for the Formation of Natural and Artificial Biomaterials
Authors: Künzle Matthias , Lach Marcel , Budiarta Made , Beck Tobias 
Published: February 2019

AbstractThe assembly of molecular building blocks into highly ordered structures is crucial, both in nature and for the development of novel functional materials. In nature, noncovalent interactions, such as hydrogen bonds or hydrophobic interactions, enable the reversible assembly of biopolymers, such as DNA or proteins. Inspired by these design principles, scientists have created biohybrid materials that employ natural building blocks and their assembly properties. Thus, structures and materials are attainable that cannot be made through other synthetic procedures. Herein, we review current concepts and highlight recent advances.
Efficient Enzymatic Cyclization of Disulfide‐Rich Peptides by Using Peptide Ligases
Authors: Schmidt Marcel , Huang Yen‐Hua , Texeira de Oliveira Eduardo F. , Toplak Ana , Wijma Hein J. , Janssen Dick B. , van Maarseveen Jan H. , Craik David J. , Nuijens Timo 
Published: February 2019

AbstractDisulfide‐rich macrocyclic peptides—cyclotides, for example—represent a promising class of molecules with potential therapeutic use. Despite their potential their efficient synthesis at large scale still represents a major challenge. Here we report new chemoenzymatic strategies using peptide ligase variants—inter alia, omniligase‐1—for the efficient and scalable one‐pot cyclization and folding of the native cyclotides MCoTI‐II, kalata B1 and variants thereof, as well as of the θ‐defensin RTD‐1. The synthesis of the kB1 variant T20K was successfully demonstrated at multi‐gram scale. The existence of several ligation sites for each macrocycle makes this approach highly flexible and facilitates both the larger‐scale manufacture and the engineering of bioactive, grafted cyclotide variants, therefore clearly offering a valuable and powerful extension of the existing toolbox of enzymes for peptide head‐to‐tail cyclization.
Management of undifferentiated high‐grade pleomorphic sarcoma of parotid region in elderly women
Authors: Sessa Michele , Tonni Daniela , Zangrandi Adriano , Oscar Redaelli de Zinis Luca , Cuda Domenico 
Published: February 2019

Key Clinical MessageUndifferentiated high‐grade pleomorphic sarcoma is a slow‐growing tumor rarely localized in the head and neck region. The treatment of UHPS should be based on large surgical resections in free margins associated with neck dissection. Postoperative radiotherapy improves local control of the disease and the prognosis quod vitam.
Three‐Dimensional Graphene/Ag Aerogel for Durable and Stable Li Metal Anodes in Carbonate‐Based Electrolytes
Authors: Yang Yang , Zhao Min , Geng Hongbo , Zhang Yufei , Fang Yanxiong , Li Chengchao , Zhao Jinbao 
Published: February 2019

AbstractThe use of Li metal as the anode for Li‐based batteries has attracted considerable attention due to its ultrahigh energy density. However, the formation of Li dendrites, uneven deposition, and huge volume changes hinder its reliable implementation. These issues become much more severe in commercial carbonate‐based electrolytes than in ether‐based electrolytes. Herein, a rationally designed three‐dimensional graphene/Ag aerogel (3D G‐Ag aerogel) is proposed for Li metal anodes with long cycle life in carbonate‐based electrolytes. The modified lithiophilic nature of G‐Ag aerogel, realized through decoration with Ag NPs, effectively decreases the energy barrier for Li nucleation, regulating uniform Li deposition behavior. Moreover, the highly flexible, conductive 3D porous architecture with hierarchical mesopores and macropores can readily accommodate deposited Li and ensures the integrity of the conductive network during cycling. Consequently, high coulombic efficiency (over 93.5 %) and a significantly long cycle life (1589 h) over 200 cycles, with a relatively high cycling capacity of 2.0 mAh cm−2, can easily be achieved, even in a carbonate‐based electrolyte. Considering the intrinsic high voltage windows of carbonate‐based electrolytes, matching the G‐Ag aerogel Li metal anode with a high‐voltage cathode can be envisaged for the fabrication of high‐energy‐density Li secondary batteries.
Microfluidic Production of Pyrophosphate Catalyzed by Mineral Membranes with Steep pH Gradients
Authors: Wang Qingpu , Barge Laura M. , Steinbock Oliver 
Published: February 2019

AbstractPyrophosphate might have functioned as an energy storage/currency molecule on early Earth, essential for the emergence of life. Here we synthesized mineral membranes involving iron(II), iron(III), and other divalent metal cations (calcium, manganese, cobalt, copper, zinc, and nickel) and tested their ability to catalyze the formation of pyrophosphate from phosphate and acetyl phosphate across steep pH gradients in microfluidic devices. We studied the chemical compositions of the precipitate membranes (which included vivianite, goethite, and green rust) using in situ and ex situ micro‐Raman spectroscopy. The yields of pyrophosphate were determined by aqueous 31P NMR spectroscopy. We found that Fe2+ and Ca2+ were the best catalysts for pyrophosphate synthesis among investigated ions; Fe3+ and mixed‐valence iron membranes were also able to promote pyrophosphate formation. In addition, the pH gradients across the membranes affected the pyrophosphate yields and the smallest pH gradient resulted in the highest yield. These results suggest a possible route of substrate phosphorylation in prebiotic hydrothermal systems.
Mechanisms of Cobalt/Phosphine‐Catalyzed Cross‐Coupling Reactions
Authors: Kreyenschmidt Friedrich , Meurer Selim E. , Koszinowski Konrad 
Published: February 2019

Abstract>The combination of CoCl2 with bidentate phosphines is known to catalyze challenging cross‐coupling and Heck‐type reactions, but the mechanisms of these valuable transformations have not been established. Here, we use electrospray‐ionization mass spectrometry to intercept the species formed in these reactions. Our results indicate that a sequence of transmetalation, reductive elimination, and redox disproportionation convert the cobalt(II) precatalyst into low‐valent cobalt complexes. These species readily transfer single electrons to alkyl bromides, which thereupon dissociate into alkyl radicals and Br−. In cross‐coupling reactions, the alkyl radicals add to the cobalt catalyst to form observable heteroleptic complexes, which release the coupling products through reductive eliminations. In the Heck‐type reactions, the low abundance of newly formed ionic species renders the analysis more difficult. Nonetheless, our results also point to the occurrence of single‐electron transfer processes and the involvement of radicals in these transformations.
Facile Synthesis of Luminescent Ir–Pt–Ir Trimetallic Complexes
Authors: Na Hanah , Song Mina , Teets Thomas S. 
Published: February 2019

AbstractA new class of luminescent, heterotrimetallic supramolecular constructs partnering two bis‐cyclometalated iridium centers with a diimine platinum acetylide center is introduced. Whereas most supramolecular constructs featuring cyclometalated iridium involve elaborate bridging ligands and are prepared under forcing conditions with low to moderate yields, the three Ir–Pt–Ir complexes described here are prepared at room temperature from simple precursors and isolated in near‐quantitative yields. ESI‐MS, NMR spectroscopy, and diffusion ordered spectroscopy confirm the identity and homogeneity of the trimetallic products. In comparison with monometallic model complexes, analysis of UV/Vis absorption, steady‐state photoluminescence and time‐resolved emission reveals the impacts of supramolecular assembly on the photophysical properties. UV/Vis absorption and cyclic voltammetry suggest perturbation of some frontier orbital energies as a result of assembly, and the emission spectra and lifetimes reveal efficient excited‐state energy transfer via a Dexter mechanism, and show that the site of luminescence (platinum or iridium) depends on the identity of the cyclometalating ligand bound to iridium.
Measurement of the Impact Force and Pressure of Water Jets under the Influence of Jet Break‐up
Authors: Fuchs Enrico , Köhler Hannes , Majschak Jens‐Peter 
Published: February 2019

AbstractUsing a new test setup, the results for the mechanical impact force and pressure of water jets of a nozzle in tubular form with different nozzle diameters (3, 4 mm), gauge pressures (1 – 6 bar) and stand‐off distances (0.5 – 5 m) are presented. It is shown that the stand‐off distance and, thus, the jet break‐up has a significant influence on the mechanical forces of water jets. An optimum stand‐off distance with regard to the maximum impact force and pressure was determined in the range of 2 – 2.5 m. As a result, a semi‐empirical equation for the description of the mean impact force was derived.
Expression of cholecystokinin by neurons in mouse spinal dorsal horn
Authors: Gutierrez‐Mecinas Maria , Bell Andrew M. , Shepherd Fraser , Polgár Erika , Watanabe Masahiko , Furuta Takahiro , Todd Andrew J. 
Published: February 2019

AbstractExcitatory interneurons account for the majority of dorsal horn neurons, and are required for perception of normal and pathological pain. We have identified largely non‐overlapping populations in laminae I‐III, based on expression of substance P, gastrin‐releasing peptide, neurokinin B, and neurotensin. Cholecystokinin (CCK) is expressed by many dorsal horn neurons, particularly in the deeper laminae. Here, we have used immunocytochemistry and in situ hybridization to characterize the CCK cells. We show that they account for ~7% of excitatory neurons in laminae I‐II, but between a third and a quarter of those in lamina III. They are largely separate from the neurokinin B, neurotensin, and gastrin‐releasing peptide populations, but show limited overlap with the substance P cells. Laminae II‐III neurons with protein kinase Cγ (PKCγ) have been implicated in mechanical allodynia following nerve injury, and we found that around 50% of CCK cells were PKCγ‐immunoreactive. Neurotensin is also expressed by PKCγ cells, and among neurons with moderate to high levels of PKCγ, ~85% expressed CCK or neurotensin. A recent transcriptomic study identified mRNA for thyrotropin‐releasing hormone in a specific subpopulation of CCK neurons, and we show that these account for half of the CCK/PKCγ cells. These findings indicate that the CCK cells are distinct from other excitatory interneuron populations that we have defined. They also show that PKCγ cells can be assigned to different classes based on neuropeptide expression, and it will be important to determine the differential contribution of these classes to neuropathic allodynia.
Brain mapping of the gonadotropin‐inhibitory hormone‐related peptide 2 with a novel antibody suggests a connection with emotional reactivity in the Japanese quail (Coturnix japonica, Temminck & Schlegel, 1849)
Authors: Poissenot Kevin , Anger Karine , Constantin Paul , Cornilleau Fabien , Lomet Didier , Tsutsui Kazuyoshi , Dardente Hugues , Calandreau Ludovic , Beltramo Massimiliano 
Published: February 2019

ABSTRACTGonadotropin‐inhibitory hormone (GnIH) is a neuropeptide first discovered in the quail brain that is involved in the control of reproductive physiology and behaviors, and stress response. GnIH gene encodes a second peptide, GnIH‐related peptide‐2 (RP2), the distribution and function of which remain unknown. We therefore studied GnIH‐RP2 distribution by immunohistochemistry using a novel antibody capable of discriminating between GnIH and GnIH‐RP2. The overall distribution of GnIH‐RP2 is similar to that of GnIH. The vast majority of labeled neurons is located in the paraventricular nucleus (PVN) of the hypothalamus. Labeling of fibers is conspicuous in the diencephalon, but present also in the mesencephalon and telencephalon. Several regions involved in the control of reproduction and stress response (the PVN, septum, bed nucleus of the stria terminalis and nucleus commissura pallii) showed a dense network of immunolabeled fibers. To investigate the potential function of GnIH‐RP2 we compared its expression in two quail lines genetically selected for divergence in their emotional reactivity. A quantitative analysis in the above‐mentioned brain regions showed that the density of fibers was similar in the two lines. However, the number of GnIH‐RP2 labeled neurons was higher in the median portion of the PVN in birds with higher emotional reactivity. These results point to a possible involvement of GnRH‐RP2 in modulating stress response and/or emotional reactivity.
Insight into the Excitation‐Dependent Fluorescence of Carbon Dots
Authors: Divya Sasi , Narayan Satya , Ainavarapu Sri Rama Koti , Khushalani Deepa 
Published: February 2019

AbstractHigh quantum yield, photoluminescence tunability, and sensitivity to the environment are a few distinct trademarks that make carbon nanodots (CDs) interesting for fundamental research, with potential to replace the prevalent inorganic semiconductor quantum dots. Currently, application and fundamental understanding of CDs are constrained because it is difficult to make a quantitative comparison among different types of CDs simply because their photoluminescence properties are directly linked to their size distribution, the surface functionalization, the carbon core structures (graphitic or amorphous) and the number of defects. Herein, we report a facile one‐step synthesis of mono‐dispersed and highly fluorescent nanometre size CDs from a ‘family’ of glucose‐based sugars. These CDs are stable in aqueous solutions with photoluminescence in the visible range. Our results show several common features in the family of CDs synthesized in that the fluorescence, in the visible region, is due to a weak absorption in the 300–400 nm from a heterogeneous population of fluorophores. Fluorescence quenching experiments suggest the existence of not only surface‐exposed fluorophores but more importantly solvent inaccessible fluorophores present within the core of CDs. Interestingly, time‐resolved fluorescence anisotropy experiments directly suggest that a fast exchange of excitation energy occurs that results in a homo‐FRET based depolarization within 150 ps of excitation.
Reversible Metal‐Hydride Transformation in Mg‐Ti‐H Nanoparticles at Remarkably Low Temperatures
Authors: Patelli Nicola , Migliori Andrea , Pasquini Luca 
Published: February 2019

AbstractWe study the kinetics of hydrogen sorption in Mg‐Ti‐H nanoparticles prepared by gas phase condensation of mixed Mg‐Ti vapors under a H2‐containing atmosphere. Four samples with different Ti contents from 14 to 63 at.% Ti are examined in the 100–150 °C range. The hydrogen absorption kinetics coupled with the formation of MgH2 can be described by a nucleation and growth model. The activation energy is in the range
kJ/mol and the rate constant (at 150 °C) increases from
s−1 to
s−1 with increasing Ti content. Hydrogen desorption is well modeled by a sequence of surface‐limited and contracting‐volume kinetics, except at the highest Ti content where nucleation and growth is observed. The activation energy of surface‐limited kinetics is
/mol. The rate constant (at 150 °C) increases from
s−1 to
s−1 with the Ti content. These results open an unexplored kinetic window for Mg‐based reversible hydrogen storage close to ambient temperature.
On the Nature of the Positronic Bond
Authors: Goli Mohammad , Shahbazian Shant 
Published: February 2019

AbstractRecently it has been proposed that the positron, the anti‐particle analog of the electron, is capable of forming an anti‐matter bond in a composite system consists of two hydride anions and a positron [Angew. Chem. Int. Ed. 57, 8859–8864 (2018)]. In order to dig into the nature of this novel bond the newly developed multi‐component quantum theory of atoms in molecules (MC‐QTAIM) is applied to this positronic system. The topological analysis reveals that this species is composed of two atoms in molecules, each containing a proton and half of the electronic and the positronic populations. Further analysis elucidates that the electron exchange phenomenon is virtually non‐existent between the two atoms and no electronic covalent bond is conceivable in between. On the other hand, it is demonstrated that the positron density enclosed in each atom is capable of stabilizing interactions with the electron density of the neighboring atom. This electrostatic interaction suffices to make the whole system bonded against all dissociation channels. Thus, the positron indeed acts like an anti‐matter glue between the two atoms.
A pilot clinical evaluation of oral mucosal dryness in dehydrated patients using a moisture‐checking device
Authors: Fukushima Yosuke , Sano Yoshie , Isozaki Yuta , Endo Mao , Tomoda Taketo , Kitamura Tomohisa , Sato Tsuyoshi , Kamijo Yoshito , Haga Yoshiyuki , Yoda Tetsuya 
Published: February 2019

AbstractThis study included 30 patients (17 males and 13 females; mean age, 73.7 ± 13.1 years) who were diagnosed with dehydration based on vital signs, skin symptoms, and blood test findings by emergency medicine physicians. First, the attending physician of our department measured oral mucosal dryness. Subsequently, the emergency medicine physician blindly divided the severity of dehydration into three stages according to clinical findings and blood test results. In this study, the oral moisture‐checking device (Mucus®; Life Co., Ltd., Saitama, Japan) was used to measure the oral mucosal dryness. We examined the oral moisture level for each dehydration severity level and the correlations of each severity level of dehydration with the measured values. Spearman's correlation coefficient (Medcalc version 11.3 for Windows) was used for statistical analysis. P < 0.05 indicated significant differences. Twenty‐six patients were diagnosed with dry mouth, and a moderate negative correlation was found between the severity of dehydration and oral moisture degree (r = −0.686). The correlation coefficient for the relationship between oral moisture degree and severity of dehydration was −0.686, indicating a negative correlation (P < .05). These results suggest that the oral mucosal dryness may be a useful index of dehydration severity.
Bright CD38 Expression by Flow Cytometric Analysis Is a Biomarker for Double/Triple Hit Lymphomas with a Moderate Sensitivity and High Specificity
Authors: Alsuwaidan Abdullah , Pirruccello Elaina , Jaso Jesse , Koduru Prasad , Garcia Rolando , Krueger JoEllen , Doucet Meggie , Chaudhry Rahman , Fuda Franklin , Chen Weina 
Published: February 2019

BackgroundHigh‐grade B‐cell lymphomas (HGBCL) with MYC and BCL2 or/and BCL6 rearrangements (R), so‐called double/triple‐hit lymphomas (DH/THL), are uncommon, clinically aggressive lymphomas that require a prompt diagnosis. We aim to identify flow cytometric immunophenotypic (IP) features of DH/THL that may aid in triaging these cases followed by a timely confirmatory cytogenetic study.MethodsWe compared the IP features of 43 cases of DH/THL to those of 55 cases of single‐hit lymphoma (SHL) and 59 cases of diffuse large B‐cell lymphoma (DLBCL) without MYC‐R (MYCneg DLBCL). We analyzed the expression patterns of CD10, CD19, CD20, CD38, and surface immunoglobulin light chain in lymphoma cells.ResultsBright CD38 expression (CD38bright) analyzed either qualitatively or semi‐quantitatively was more common in DH/THL (56%) than in MYCneg DLBCL (17%) but less common compared to SHL (82%), indicating that CD38bright can serve as a biomarker for DH/THL. Additionally, CD38bright may be a better indicator for predicting DH/THL‐BCL2 than DHL‐BCL6, and very bright CD38 expression was exclusive to MYC rearranged lymphomas. The expression patterns of other markers were similar among these lymphoma groups.ConclusionsCD38bright is a biomarker associated with DH/THL with a moderate sensitivity (~50%) and high specificity (~90%). While this marker cannot be used as a screening tool, awareness of this correlation may aid in expediting the diagnosis and prioritizing FISH testing in resource limited settings or situations when samples are limited. Future studies to combine immunohistochemical markers are needed to further enhance the predictive power of CD38bright in diagnosing DH/THL. © 2019 International Clinical Cytometry Society