bluuebunny/crossref_metadata_2025_split huggingface dataset:
Metformin exerts multitarget antileukemia activity in JAK2V617F-positive myeloproliferative neoplasms
Authors: Machado-Neto João Agostinho , Fenerich Bruna Alves , Scopim-Ribeiro Renata , Eide Christopher A. , Coelho-Silva Juan Luiz , Dechandt Carlos Roberto Porto , Fernandes Jaqueline Cristina , Rodrigues Alves Ana Paula Nunes , Scheucher Priscila Santos , Simões Belinda Pinto , Alberici Luciane Carla , de Figueiredo Pontes Lorena Lôbo , Tognon Cristina E. , Druker Brian J. , Rego Eduardo Magalhães , Traina Fabiola 
Published: February 2018

AbstractThe recurrent gain-of-function JAK2V617F mutation confers growth factor-independent proliferation for hematopoietic cells and is a major contributor to the pathogenesis of myeloproliferative neoplasms (MPN). The lack of complete response in most patients treated with the JAK1/2 inhibitor ruxolitinib indicates the need for identifying novel therapeutic strategies. Metformin is a biguanide that exerts selective antineoplastic activity in hematological malignancies. In the present study, we investigate and compare effects of metformin and ruxolitinib alone and in combination on cell signaling and cellular functions in JAK2V617F-positive cells. In JAK2V617F-expressing cell lines, metformin treatment significantly reduced cell viability, cell proliferation, clonogenicity, and cellular oxygen consumption and delayed cell cycle progression. Metformin reduced cyclin D1 expression and RB, STAT3, STAT5, ERK1/2 and p70S6K phosphorylation. Metformin plus ruxolitinib demonstrated more intense reduction of cell viability and induction of apoptosis compared to monotherapy. Notably, metformin reduced Ba/F3 JAK2V617F tumor burden and splenomegaly in Jak2V617F knock-in-induced MPN mice and spontaneous erythroid colony formation in primary cells from polycythemia vera patients. In conclusion, metformin exerts multitarget antileukemia activity in MPN: downregulation of JAK2/STAT signaling and mitochondrial activity. Our exploratory study establishes novel molecular mechanisms of metformin and ruxolitinib action and provides insights for development of alternative/complementary therapeutic strategies for MPN.
Arginase-II activates mTORC1 through myosin-1b in vascular cell senescence and apoptosis
Authors: Yu Yi , Xiong Yuyan , Montani Jean-Pierre , Yang Zhihong , Ming Xiu-Fen 
Published: February 2018

AbstractType-II L-arginine:ureahydrolase, arginase-II (Arg-II), is shown to activate mechanistic target of rapamycin complex 1 (mTORC1) pathway and contributes to cell senescence and apoptosis. In an attempt to elucidate the underlying mechanism, we identified myosin-1b (Myo1b) as a mediator. Overexpression of Arg-II induces re-distribution of lysosome and mTOR but not of tuberous sclerosis complex (TSC) from perinuclear area to cell periphery, dissociation of TSC from lysosome and activation of mTORC1-ribosomal protein S6 kinase 1 (S6K1) pathway. Silencing Myo1b prevents all these alterations induced by Arg-II. By overexpressing Myo1b or its mutant with point mutation in its pleckstrin homology (PH) domain we further demonstrate that this effect of Myo1b is dependent on its PH domain that is required for Myo1b-lysosome association. Notably, Arg-II promotes association of Myo1b with lysosomes. In addition, we show that in senescent vascular smooth muscle cells with elevated endogenous Arg-II, silencing Myo1b prevents Arg-II-mediated lysosomal positioning, dissociation of TSC from lysosome, mTORC1 activation and cell apoptosis. Taken together, our study demonstrates that Myo1b mediates the effect of Arg-II in activating mTORC1-S6K1 through promoting peripheral lysosomal positioning, that results in spatial separation and thus dissociation of TSC from lysosome, leading to hyperactive mTORC1-S6K1 signaling linking to cellular senescence/apoptosis.
Role of autophagy in modulating post-maturation aging of mouse oocytes
Authors: Lin Fei-Hu , Zhang Wei-Ling , Li Hong , Tian Xiao-Dan , Zhang Jie , Li Xiao , Li Chuan-Yong , Tan Jing-He 
Published: February 2018

AbstractMechanisms for post-maturation oocyte aging (PMOA) are not fully understood, and whether autophagy plays any role in PMOA is unknown. To explore the role of autophagy in PMOA, expression of autophagosomes and effects of the autophagy (macro-autophagy) activity on PMOA were observed in mouse oocytes. Oocyte activation rates and active caspase-3 levels increased continuously from 0 to 18 h of in vitro aging. While levels of microtubule-associated protein light chain 3 (LC3)-II increased up to 12 h and decreased thereafter, contents of p62 decreased from 0 to 12 h and then elevated to basal level by 18 h. However, the LC3-II/I ratio remained unchanged following aging in different media or for different times. During in vitro aging up to 12 h, upregulating autophagy with rapamycin or lithium chloride decreased activation susceptibility, cytoplasmic calcium, p62 contents, oxidative stress, caspase-3 activation and cytoplasmic fragmentation while increasing developmental competence, LC3-II contents, LC3-II/I ratio, mitochondrial membrane potential, spindle/chromosome integrity and normal cortical granule distribution. Downregulating autophagy with 3-methyladenine (3-MA) produced opposite effects on all these parameters except cytoplasmic fragmentation. After 12 h of aging culture, however, regulating autophagy with either rapamycin/lithium chloride or 3-MA had no impact on oocyte activation susceptibility. It is concluded that autophagy plays an important role in regulating PMOA. Thus, during the early stage of PMOA, autophagy increases as an adaptive response to prevent further apoptosis, but by the late stage of PMOA, the activation of more caspases blocks the autophagic process leading to severer apoptosis.
Genetic tagging of active neurons in auditory cortex reveals maternal plasticity of coding ultrasonic vocalizations
Authors: Tasaka Gen-ichi , Guenthner Casey J. , Shalev Amos , Gilday Omri , Luo Liqun , Mizrahi Adi 
Published: February 2018

AbstractCortical neurons are often functionally heterogeneous even for molecularly defined subtypes. In sensory cortices, physiological responses to natural stimuli can be sparse and vary widely even for neighboring neurons. It is thus difficult to parse out circuits that encode specific stimuli for further experimentation. Here, we report the development of a Cre-reporter mouse that allows recombination for cellular labeling and genetic manipulation, and use it with an activity-dependent Fos-CreERT2 driver to identify functionally active circuits in the auditory cortex. In vivo targeted patch recordings validate our method for neurons responding to physiologically relevant natural sounds such as pup wriggling calls and ultrasonic vocalizations (USVs). Using this system to investigate cortical responses in postpartum mothers, we find a transient recruitment of neurons highly responsive to USVs. This subpopulation of neurons has distinct physiological properties that improve the coding efficiency for pup USV calls, implicating it as a unique signature in parental plasticity.
Cell-based glycan arrays for probing glycan–glycan binding protein interactions
Authors: Briard Jennie Grace , Jiang Hao , Moremen Kelley W. , Macauley Matthew Scott , Wu Peng 
Published: February 2018

AbstractGlycan microarrays provide a high-throughput means of profiling the interactions of glycan-binding proteins with their ligands. However, the construction of current glycan microarray platforms is time consuming and expensive. Here, we report a fast and cost-effective method for the assembly of cell-based glycan arrays to probe glycan–glycan-binding protein interactions directly on the cell surface. Chinese hamster ovary cell mutants with a narrow and relatively homogeneous repertoire of glycoforms serve as the foundation platforms to develop these arrays. Using recombinant glycosyltransferases, sialic acid, fucose, and analogs thereof are installed on cell-surface glycans to form cell-based arrays displaying diverse glycan epitopes that can be probed with glycan-binding proteins by flow cytometry. Using this platform, high-affinity glycan ligands are discovered for Siglec-15—a sialic acid-binding lectin involved in osteoclast differentiation. Incubating human osteoprogenitor cells with cells displaying a high-affinity Siglec-15 ligand impairs osteoclast differentiation, demonstrating the utility of this cell-based glycan array technology.
All-optical control and super-resolution imaging of quantum emitters in layered materials
Authors: Kianinia Mehran , Bradac Carlo , Sontheimer Bernd , Wang Fan , Tran Toan Trong , Nguyen Minh , Kim Sejeong , Xu Zai-Quan , Jin Dayong , Schell Andreas W. , Lobo Charlene J. , Aharonovich Igor , Toth Milos 
Published: February 2018

AbstractLayered van der Waals materials are emerging as compelling two-dimensional platforms for nanophotonics, polaritonics, valleytronics and spintronics, and have the potential to transform applications in sensing, imaging and quantum information processing. Among these, hexagonal boron nitride (hBN) is known to host ultra-bright, room-temperature quantum emitters, whose nature is yet to be fully understood. Here we present a set of measurements that give unique insight into the photophysical properties and level structure of hBN quantum emitters. Specifically, we report the existence of a class of hBN quantum emitters with a fast-decaying intermediate and a long-lived metastable state accessible from the first excited electronic state. Furthermore, by means of a two-laser repumping scheme, we show an enhanced photoluminescence and emission intensity, which can be utilized to realize a new modality of far-field super-resolution imaging. Our findings expand current understanding of quantum emitters in hBN and show new potential ways of harnessing their nonlinear optical properties in sub-diffraction nanoscopy.
FcαRI co-stimulation converts human intestinal CD103+ dendritic cells into pro-inflammatory cells through glycolytic reprogramming
Authors: Hansen Ivo S. , Krabbendam Lisette , Bernink Jochem H. , Loayza-Puch Fabricio , Hoepel Willianne , van Burgsteden Johan A. , Kuijper Elsa C. , Buskens Christianne J. , Bemelman Willem A. , Zaat Sebastiaan A. J. , Agami Reuven , Vidarsson Gestur , van den Brink Gijs R. , de Jong Esther C. , Wildenberg Manon E. , Baeten Dominique L. P. , Everts Bart , den Dunnen Jeroen 
Published: February 2018

AbstractCD103+ dendritic cells (DC) are crucial for regulation of intestinal tolerance in humans. However, upon infection of the lamina propria this tolerogenic response is converted to an inflammatory response. Here we show that immunoglobulin A (IgA) immune complexes (IgA-IC), which are present after bacterial infection of the lamina propria, are important for the induction of inflammation by the human CD103+SIRPα+ DC subset. IgA-IC, by recognition through FcαRI, selectively amplify the production of proinflammatory cytokines TNF, IL-1β and IL-23 by human CD103+ DCs. These cells then enhance inflammation by promoting Th17 responses and activating human intestinal innate lymphoid cells 3. Moreover, FcαRI-induced cytokine production is orchestrated via upregulation of cytokine translation and caspase-1 activation, which is dependent on glycolytic reprogramming mediated by kinases Syk, PI3K and TBK1-IKKε. Our data suggest that the formation of IgA-IC in the human intestine provides an environmental cue for the conversion of a tolerogenic to an inflammatory response.
Nanodroplet processing platform for deep and quantitative proteome profiling of 10–100 mammalian cells
Authors: Zhu Ying , Piehowski Paul D. , Zhao Rui , Chen Jing , Shen Yufeng , Moore Ronald J. , Shukla Anil K. , Petyuk Vladislav A. , Campbell-Thompson Martha , Mathews Clayton E. , Smith Richard D. , Qian Wei-Jun , Kelly Ryan T. 
Published: February 2018

AbstractNanoscale or single-cell technologies are critical for biomedical applications. However, current mass spectrometry (MS)-based proteomic approaches require samples comprising a minimum of thousands of cells to provide in-depth profiling. Here, we report the development of a nanoPOTS (nanodroplet processing in one pot for trace samples) platform for small cell population proteomics analysis. NanoPOTS enhances the efficiency and recovery of sample processing by downscaling processing volumes to <200 nL to minimize surface losses. When combined with ultrasensitive liquid chromatography-MS, nanoPOTS allows identification of ~1500 to ~3000 proteins from ~10 to ~140 cells, respectively. By incorporating the Match Between Runs algorithm of MaxQuant, >3000 proteins are consistently identified from as few as 10 cells. Furthermore, we demonstrate quantification of ~2400 proteins from single human pancreatic islet thin sections from type 1 diabetic and control donors, illustrating the application of nanoPOTS for spatially resolved proteome measurements from clinical tissues.
In situ generation of intercalated membranes for efficient gas separation
Authors: Kang Zixi , Wang Sasa , Fan Lili , Zhang Minghui , Kang Wenpei , Pang Jia , Du Xinxin , Guo Hailing , Wang Rongming , Sun Daofeng 
Published: February 2018

AbstractMembranes with well-defined pore structure which have thin active layers may be promising materials for efficient gas separation. Graphene oxide (GO) materials have potential applications in the field of membrane separation. Here we describe a strategy for the construction of ultra-thin and flexible HKUST-1@GO intercalated membranes, where HKUST-1 is a copper-based metal–organic framework with coordinatively unsaturated metal sites, with simultaneous and synergistic modulation of permeance and selectivity to achieve high H2/CO2 separation. CuO nanosheets@GO membranes are fabricated layer-by-layer via repeated filtration cycles, then transformed to HKUST-1@GO membranes upon in situ reaction with linkers. The HKUST-1@GO membranes show enhanced performance for gas separation of H2/CO2 mixture. The number of filtration cycles is optimized to obtain H2 permeance of 5.77 × 10−7 mol m−2 s−1 Pa−1 and H2/CO2 selectivity of 73.2. Our work provides a facile strategy for the construction of membranes based on metal–organic frameworks and GO, which may be applied in the preparation of flexible membranes for gas separation applications.
Visible chiral discrimination via macroscopic selective assembly
Authors: Zheng Yongtai , Kobayashi Yuichiro , Sekine Tomoko , Takashima Yoshinori , Hashidzume Akihito , Yamaguchi Hiroyasu , Harada Akira 
Published: February 2018

AbstractThe transfer of chirality from individual molecules to macroscopic objects, and the recognition of chirality on the macroscopic scale have potential for many practical applications, but they are still key challenges for the chiral research community. Here we present a strategy for visible chiral recognition by macroscopic assembly using polyacrylamide-based gels modified with β-cyclodextrin (βCD-gel) and d- or l-tryptophan (homochiral d- or l-Trp-gel), which differs from most methods reported, e.g., colorimetric or chromogenic methods, fluorescence, gel formation and collapse. The circular dichroism spectra demonstrate that the chirality of Trp molecules is successfully transferred and amplified in the corresponding Trp-gels. The chirality of the d- and l-Trp-gels is macroscopically recognized by the βCD-gel selectivity in aqueous NaCl through the amplification of interfacial enantioselective host–guest interactions.
Coherent vibrations in methanol cation probed by periodic H3+ ejection after double ionization
Authors: Ando Toshiaki , Shimamoto Akihiro , Miura Shun , Iwasaki Atsushi , Nakai Katsunori , Yamanouchi Kaoru 
Published: February 2018

AbstractWhen hydrocarbon molecules are exposed to an intense laser field, triatomic hydrogen molecular ion, H3+, is ejected. Here we describe pump–probe measurements of the ejection of H3+ from methanol dication with high temporal resolution using intense few-cycle laser pulses and find a long-lasting periodic increase in the yield of H3+. We show that H3+ ejection is the lowest energy decomposition channel and that its yield is enhanced each time when the vibrational wave packet coming back to the inner turning point of methanol cation is projected onto the dication potential energy surface. We also show that the time-resolved measurement of the yield of H3+ is an efficient tool not only for probing ultrafast nuclear dynamics of hydrocarbon cations but also for deriving vibrational frequencies of hydrocarbon cations with high precision.
Acute Disseminated Encephalomyelitis as a Complication of Scrub Typhus in Children
Authors: Roy Soumya , Chakrabartty Subroto 
Published: February 2018

AbstractScrub typhus is a re-emerging threat throughout the world. The spectra of clinical pictures and possible complications are both varied and being increasingly reported. Acute disseminated encephalomyelitis (ADEM) is an infrequent demyelinating disorder of the central nervous system that is precipitated by infections and immunizations. There are only two documented cases of ADEM-associated scrub typhus published in the medical literature. We report the first pediatric case wherein a 5-year-old boy presented with high fever, altered sensorium, seizure, quadriparesis, and neck rigidity. He was ultimately diagnosed as a case of scrub typhus with ADEM. After treatment with intravenous doxycycline and methylprednisolone, the fever subsided but residual neurodeficits, such as inability to sit, stand, and talk, as well as bowel bladder dysfunctions persisted. He was subsequently transferred to long-term rehabilitation care.
Bilateral Striatal Necrosis after Sydenham's Chorea in a 7-Year-Old Boy: A 2-Year Follow-Up
Authors: Canavese C. , Casabianca M. , Olivieri C. , Mancini S. , Migliore G. , Versace A. , Tocchet A. , Vitiello B. , Davico C. 
Published: February 2018

AbstractChild bilateral striatal necrosis (BSN) is a rare and etiologically heterogeneous condition. An association with group A streptococcus (GAS) infection was previously reported in two cases of BSN in infancy and early childhood. We here report on a 7-year-old boy who developed chorea and dystonia 20 days after symptomatic recovery from Sydenham's chorea. Repeated brain magnetic resonance imaging scans, obtained before, soon after the onset of the post-Sydenham symptoms, and 1 year later were consistent with an evolution from bilateral striatal microbleeding to necrosis, and consequently reduced basal ganglia volume and enlargement of the frontal horns. No support was found for other possible autoimmune, infectious, metabolic, toxic or genetic etiologies for BSN. Prednisone treatment was instituted and continued for 1 year. Two years after the onset of the post-Sydenham symptoms, the child, although much improved, still has generalized dystonic–choreic movements. This case confirms and extends into school age, the link between GAS and BSN.
Targeting Hepatitis D
Authors: Rizzetto Mario 
Published: February 2018

AbstractNew therapeutic strategies to treat chronic hepatitis D are directed to deprive the hepatitis D virus (HDV) of functions necessary to complete its life cycle that are provided by the hepatitis B virus (HBV) and by the host. Current options are (1) the block by the synthetic peptide Myrcludex B of HBV surface antigen (HBsAg) entry into cells through the inhibition of the sodium taurocholate cotransporting receptor; (2) the inhibition with lonafarnib of the farnesylation of the large HD antigen, required for virion assembly; (3) the presumed reduction by the nucleic acid polymer REP 2139 of the release of the HBsAg and subviral HBV particles necessary for HD virion morphogenesis. Lonafarnib and Myrcludex in monotherapy reduced serum HDV-RNA but did not reduce the HBsAg and HD viremia rebounded after therapy; they may provide additional efficacy to pegylated interferon alpha (Peg IFN-α) therapy. Treatment with REP-2139 in combination with Peg IFN-α induced a sustained clearance both of the HDV-RNA and HBsAg in 5 of 12 patients, providing the best interim results so far obtained in the therapy of chronic hepatitis D.
Development and Validation of a Natural Language Processing Tool to Identify Patients Treated for Pneumonia across VA Emergency Departments
Authors: Jones B. , South B. , Shao Y. , Lu C.C. , Leng J. , Sauer B. , Gundlapalli A. , Samore M. , Zeng Q. 
Published: February 2018

Background Identifying pneumonia using diagnosis codes alone may be insufficient for research on clinical decision making. Natural language processing (NLP) may enable the inclusion of cases missed by diagnosis codes.
Objectives This article (1) develops a NLP tool that identifies the clinical assertion of pneumonia from physician emergency department (ED) notes, and (2) compares classification methods using diagnosis codes versus NLP against a gold standard of manual chart review to identify patients initially treated for pneumonia.
Methods Among a national population of ED visits occurring between 2006 and 2012 across the Veterans Affairs health system, we extracted 811 physician documents containing search terms for pneumonia for training, and 100 random documents for validation. Two reviewers annotated span- and document-level classifications of the clinical assertion of pneumonia. An NLP tool using a support vector machine was trained on the enriched documents. We extracted diagnosis codes assigned in the ED and upon hospital discharge and calculated performance characteristics for diagnosis codes, NLP, and NLP plus diagnosis codes against manual review in training and validation sets.
Results Among the training documents, 51% contained clinical assertions of pneumonia; in the validation set, 9% were classified with pneumonia, of which 100% contained pneumonia search terms. After enriching with search terms, the NLP system alone demonstrated a recall/sensitivity of 0.72 (training) and 0.55 (validation), and a precision/positive predictive value (PPV) of 0.89 (training) and 0.71 (validation). ED-assigned diagnostic codes demonstrated lower recall/sensitivity (0.48 and 0.44) but higher precision/PPV (0.95 in training, 1.0 in validation); the NLP system identified more “possible-treated” cases than diagnostic coding. An approach combining NLP and ED-assigned diagnostic coding classification achieved the best performance (sensitivity 0.89 and PPV 0.80).
Conclusion System-wide application of NLP to clinical text can increase capture of initial diagnostic hypotheses, an important inclusion when studying diagnosis and clinical decision-making under uncertainty.
Does Transjugular Intrahepatic Portosystemic Shunt Stent Differentially Improve Survival in a Subset of Cirrhotic Patients?
Authors: Trebicka Jonel 
Published: February 2018

AbstractDoes transjugular intrahepatic portosystemic shunt stent (TIPS) improve survival in a subgroup of patients? Yes. TIPS nearly halves portal pressure and increases the effective blood volume. In cases of acute variceal hemorrhage and with a high risk of treatment failure, defined as either hepatic venous pressure gradient higher than 20 mm Hg, Child B with active bleeding at the endoscopy, or Child C with less than 14 points, early or preemptive placement of TIPS (within 72 hours) improves survival. Also, in suitable patients with intractable or refractory ascites, TIPS improves survival if placed early in the course of treatment. While TIPS does not improve survival in other situations, it improves disease management, especially in patients without TIPS contraindications but with refractory bleeding, early rebleeding, portal vein thrombosis, and hepatorenal syndrome. Experience gained at the centers and follow-up of TIPS patients are key features that improve outcome. Important factors for selection and follow-up include cardiac function, inflammation, sarcopenia, age, and early evaluation for liver transplantation.