bluuebunny/crossref_metadata_2025_split huggingface dataset:
Phase Ib study evaluating safety and clinical activity of the anti-HER3 antibody lumretuzumab combined with the anti-HER2 antibody pertuzumab and paclitaxel in HER3-positive, HER2-low metastatic breast cancer
Authors: Schneeweiss Andreas , Park-Simon Tjoung-Won , Albanell Joan , Lassen Ulrik , Cortés Javier , Dieras Veronique , May Marcus , Schindler Christoph , Marmé Frederik , Cejalvo Juan Miguel , Martinez-Garcia Maria , Gonzalez Iria , Lopez-Martin Jose , Welt Anja , Levy Christelle , Joly Florence , Michielin Francesca , Jacob Wolfgang , Adessi Céline , Moisan Annie , Meneses-Lorente Georgina , Racek Tomas , James Ian , Ceppi Maurizio , Hasmann Max , Weisser Martin , Cervantes Andrés 
Published: January 2018

Summary
Purpose To investigate the safety and clinical activity of comprehensive human epidermal growth factor receptor (HER) family receptor inhibition using lumretuzumab (anti-HER3) and pertuzumab (anti-HER2) in combination with paclitaxel in patients with metastatic breast cancer (MBC). Methods This phase Ib study enrolled 35 MBC patients (first line or higher) with HER3-positive and HER2-low (immunohistochemistry 1+ to 2+ and in-situ hybridization negative) tumors. Patients received lumretuzumab (1000 mg in Cohort 1; 500 mg in Cohorts 2 and 3) plus pertuzumab (840 mg loading dose [LD] followed by 420 mg in Cohorts 1 and 2; 420 mg without LD in Cohort 3) every 3 weeks, plus paclitaxel (80 mg/m2 weekly in all cohorts). Patients in Cohort 3 received prophylactic loperamide treatment. Results Diarrhea grade 3 was a dose-limiting toxicity of Cohort 1 defining the maximum tolerated dose of lumretuzumab when given in combination with pertuzumab and paclitaxel at 500 mg every three weeks. Grade 3 diarrhea decreased from 50% (Cohort 2) to 30.8% (Cohort 3) with prophylactic loperamide administration and omission of the pertuzumab LD, nonetheless, all patients still experienced diarrhea. In first-line MBC patients, the objective response rate in Cohorts 2 and 3 was 55% and 38.5%, respectively. No relationship between HER2 and HER3 expression or somatic mutations and clinical response was observed. Conclusions Combination treatment with lumretuzumab, pertuzumab and paclitaxel was associated with a high incidence of diarrhea. Despite the efforts to alter dosing, the therapeutic window remained too narrow to warrant further clinical development. Trial registration: on ClinicalTrials.gov with the identifier NCT01918254 first registered on 3rd July
2013.
The effect of different iron concentrations on lead accumulation in hydroponically grown Matthiola flavida Boiss
Authors: Heidari Dehno Amin , Mohtadi Ahmad 
Published: January 2018

AbstractThe general relationship between heavy metals and mineral nutrition of plants grown in polluted environments is one of the most important factors for modifying the toxic properties of these metals. To study the effect of iron and lead pollution on the growth of Matthiola flavida a factorial research was undertaken in the form of a completely randomized design with four replications in hydroponic culture. After germination, seedlings were transferred to a hydroponic culture. During the pre‐treatment step, a series of plants contained enough iron (+Fe), whereas the second series was without iron (−Fe). After the pre‐treatment step, both series of plants were treated with three levels of iron as FeEDDHA and two levels of lead as Pb(NO3)2. The results showed that in both series of plants, lead reduced the root growth, shoot height, shoot and root dry weight. For 5 µM lead concentration, with increasing concentration of iron in the nutrient solution, concentration of lead in the roots and shoots decreased. For 1 µM concentration of lead, increasing the iron concentration in the nutrient solution reduced the concentration of lead in the roots, but had no significant effect on the amount of lead in shoots. Lead accumulation in shoots and roots of plants with Fe was more than plants without Fe. Also, in low concentrations of iron, the amount of iron in shoot increased with the increase of lead concentration in the nutrient solution. The results showed that in lead pollution, iron has a positive effect on investigated traits.
Fault Rupture Directivity of Large Earthquakes in Himalaya
Authors: Srivastava H. N. , Verma Mithila , Bansal B. K. 
Published: January 2018

ABSTRACT
The paper examines the predominant fault rupture directivity during large earthquakes in different sectors of the Himalaya which influences strong ground motion and damage scenario. The nature of the faulting of earthquakes vis-à-vis their rupture directivity has been discussed. It is found that the rupture directivity near the Indo-Eurasian plate boundary varies from place to place i.e. either along the strike direction of the faults or at right angles to it. The secondary meizoseismal areas as observed for 1505 Dharchula, 1803 Uttarakhand, 1905 Kangra earthquakes in the Himalaya and 2001 Bhuj earthquake in stable continental region suggest that they are a fairly good indicator of predominant rupture directivity since the latter accentuates the site response up to a longer distance. The resulting larger ground motions, therefore, need to be incorporated in the design of engineering structures by suitable modifications in the BIS code.
Plug Shaped Burrows Conichnus - Conostichus from the Late Cretaceous of Bagh Group, Gujarat, Western India
Authors: Patel Satish J. , Shitole Apurva D. , Joseph Jaquilin K. 
Published: January 2018

ABSTRACT
Plug-shaped ichnofossils Conichnus conicus, Conostichus broadheadi and C. stouti are found in the intercalated micritic sandstone and sandy allochemic limestone shale sequence of Bagh Group, Narmada district, Gujarat. These ichnospecies occur at two stratigraphic levels and shows distinct morphological features interpreted as resting/dwelling structures of sea anemone. The occurrence of these ichnospecies along with oyster fossils genera like Bosostrea and Indostrea indicate shallow marine environment.
Paleoseismological Investigations along Joggers Park Fault, Port Blair, South Andaman: Implications towards Delineation of Blind Thrusting and Related Crustal Deformation through Ground Penetrating Radar (GPR) and Electrical Resistivity Techniques (ERT and VES)
Authors: Bhat Gulam Rasool , Balaji S. , Bali Bikram S. , Iqbal Vazeem , Balakrishna  , Hussain Hamid 
Published: January 2018

ABSTRACT
A comprehensive paleoseismological investigations was carried out along Joggers Park Fault (striking NW-SE) reveals pervasive traces of active compressional tectonics (blind thrusting) and shallow-surface recent tectonic signatures along the fault. The geometry and trends in the tectonic deformation of the blind zone (shallow-subsurface stratigraphy) were examined with GPR and electrical resistivity tomography (ERT) and vertical electrical sounding (VES), strongly demonstrates severe tectonic deformation (persistent tectonic style) from Quaternary to Holocene times in a compressive stress regime. The surface manifestation of deformation (topographic expression) along the fault can be marked as hanging wall uplift and can be visually observed in the exposed sections at nearly half kilometer distance from the table land of Joggers Park in the form of a well-defined disconnected high angle thrust fault scarp (reverse fault). The reverse fault kinematically and intimately linked with underlying fault geometry provides adduced evidence to evaluate strike displacement profiles (displacement length relationship) along the fault. In addition, deformed stacked colluvial wedge below the scarp represents a powerful basis to calibrate recent and long term slip rates of the underlying fault.
Bearing of Structural Anisotropy on Deformation and Mechanical Response of Rocks: An Experimental Example of Rocksalt Deformation Under Variable Compression Rates
Authors: Dubey R. K. 
Published: January 2018

ABSTRACT
The deformation and mechanical responses of rocks are prime concern in development of varieties of civil and mining engineering structures. The deformation and mechanical properties of both natural and artificial materials are strongly depend on mineral constituents and their arrangements, temperatures and pressures, stress rates and structural anisotropy. This study elaborates an understanding of structural anisotropy, compression rates and mechanical attributes relationship in rocks with specific examples of deformed rocksalt. The cubical samples (5X5X5 cm3) with three kinds of structural anisotropy were subjected to quasistatic compressive stress at rates 0.00035 MPa/min, 0.0035 MPa/min, 0.035 MPa/min, 0.35 MPa/min, 3.5MPa/min, 5 MPa/min, 7MPa/min and 9 MPa/min on servo-controlled Material Testing System (MTS). The stress-strain curves prepared from deformation of rocksalt’s samples under different rates of compressions are used to determine major mechanical parameters viz., strengths, strains, and modulus of elasticity. A micro-mechanical en-echelon crack array model is proposed to explain the influence of structural anisotropy on deformation patterns and mechanical properties of rocksalt. According to the proposed model the deformation progresses due to different proportional contributions of tensile and shear crack arrays under the influence of structural anisotropy. The control of structural anisotropy loses with respect to increment in rate of compression with enhance contribution of shear crack arrays in comparison to tensile crack arrays and ultimately fails in shear where the structurally anisotropic rock show isotropic behaviour.
Psychosocial characteristics as potential predictors of suicide in adults: an overview of the evidence with new results from prospective cohort studies
Authors: Batty G. David , Kivimäki Mika , Bell Steven , Gale Catharine R. , Shipley Martin , Whitley Elise , Gunnell David 
Published: January 2018

AbstractIn this narrative overview of the evidence linking psychosocial factors with future suicide risk, we collected results from published reports of prospective studies with verified suicide events (mortality or, less commonly, hospitalisation) alongside analyses of new data. There is abundant evidence indicating that low socioeconomic position, irrespective of the economic status of the country in question, is associated with an increased risk of suicide, including the suggestion that the recent global economic recession has been responsible for an increase in suicide deaths and, by proxy, attempts. Social isolation, low scores on tests of intelligence, serious mental illness (both particularly strongly), chronic psychological distress, and lower physical stature (a marker of childhood exposures) were also consistently related to elevated suicide rates. Although there is some circumstantial evidence for psychosocial stress, personality disposition, and early-life characteristics such as bullying being risk indices for suicide, the general paucity of studies means it is not currently possible to draw clear conclusions about their role. Most suicide intervention strategies have traditionally not explored the modification of psychosocial factors, partly because evidence linking psychosocial factors with suicide risk is, as shown herein, largely in its infancy, or, where is does exist, for instance for intelligence and personality disposition, the characteristics in question do not appear to be easily malleable.
SAMHD1 is recurrently mutated in T-cell prolymphocytic leukemia
Authors: Johansson Patricia , Klein-Hitpass Ludger , Choidas Axel , Habenberger Peter , Mahboubi Bijan , Kim Baek , Bergmann Anke , Scholtysik René , Brauser Martina , Lollies Anna , Siebert Reiner , Zenz Thorsten , Dührsen Ulrich , Küppers Ralf , Dürig Jan 
Published: January 2018

AbstractT-cell prolymphocytic leukemia (T-PLL) is an aggressive malignancy with a median survival of the patients of less than two years. Besides characteristic chromosomal translocations, frequent mutations affect the ATM gene, JAK/STAT pathway members, and epigenetic regulators. We here performed a targeted mutation analysis for 40 genes selected from a RNA sequencing of 10 T-PLL in a collection of 28 T-PLL, and an exome analysis of five further cases. Nonsynonymous mutations were identified in 30 of the 40 genes, 18 being recurrently mutated. We identified recurrently mutated genes previously unknown to be mutated in T-PLL, which are SAMHD1, HERC1, HERC2, PRDM2, PARP10, PTPRC, and FOXP1. SAMHD1 regulates cellular deoxynucleotide levels and acts as a potential tumor suppressor in other leukemias. We observed destructive mutations in 18% of cases as well as deletions in two further cases. Taken together, we identified additional genes involved in JAK/STAT signaling (PTPRC), epigenetic regulation (PRDM2), or DNA damage repair (SAMHD1, PARP10, HERC1, and HERC2) as being recurrently mutated in T-PLL. Thus, our study considerably extends the picture of pathways involved in molecular pathogenesis of T-PLL and identifies the tumor suppressor gene SAMHD1 with ~20% of T-PLL affected by destructive lesions likely as major player in T-PLL pathogenesis.
SOCE induced calcium overload regulates autophagy in acute pancreatitis via calcineurin activation
Authors: Zhu Zhen-Dong , Yu Tao , Liu Hua-Jing , Jin Jing , He Jun 
Published: January 2018

AbstractAcute pancreatitis (AP) is an acute inflammatory process of the pancreas that is characterized by inflammation, edema, vacuolization and necrosis, which has significant morbidity and lethality. The pathogenesis of AP has not been established completely. An early and critical feature of AP is the aberrant signaling of Calcium (Ca2+) within the pancreatic acinar cell, termed Ca2+ overload. Store-operated Ca2+ (SOC) channels are the principal Ca2+ influx channels that contribute to Ca2+ overload in pancreatic acinar cells. Store-operated Ca2+ entry (SOCE) has been proved to be a key pathogenic step in AP development that leads to trypsin activation, inflammation and vacuolization. However, the molecular mechanisms are still poorly understood. By establishing Ca2+ overload model and mouse AP model using caerulein, we found that caerulein triggered SOCE via inducing interaction between STIM1 and Orai1, which activated calcineurin (CaN); CaN activated the nuclear factor of activated T cells (NFAT) and transcription factor EB (TFEB), thus promoting the transcriptional activation of multiple chemokines genes and autophagy-associated genes respectively. To the best of our knowledge, this is the first evidence showing that SOCE activates TFEB via CaN activation, which may have noticeable longer-term effects on autophagy and vacuolization in AP development. Our findings reveal the role for SOCE/CaN in AP development and provide potential targets for AP treatment.
Autophagy promotes MSC-mediated vascularization in cutaneous wound healing via regulation of VEGF secretion
Authors: An Y. , Liu W. J. , Xue P. , Ma Y. , Zhang L. Q. , Zhu B. , Qi M. , Li L. Y. , Zhang Y. J. , Wang Q. T. , Jin Y. 
Published: January 2018

AbstractVascularization deficiency caused a lot of diseases, such as diabetes ulcer and myocardial infarction. Mesenchymal stem cells (MSCs), with the self-renewal and multipotent differentiation capacities, have been used for many diseases treatment through regulation microenvironment. Numerous studies reported that MSCs transplantation could largely improve cutaneous wound healing via paracrine secretion of growth factors. However, whether MSCs take part in the angiogenesis process directly remains elusive. Previous study proved that autophagy inhibited immunosuppressive function of MSCs and prevented the degradation of MSCs function in inflammatory and senescent microenvironment. Here, we proved that autophagy determines the therapeutic effect of MSCs in cutaneous wound healing through promoting endothelial cells angiogenesis and demonstrated that the paracrine of vascular endothelial growth factor (VEGF) in MSCs was required in wound site. We further revealed that autophagy enhanced the VEGF secretion from MSCs through ERK phosphorylation directly. Collectively, we put forward that autophagy mediated paracrine of VEGF plays a central role in MSCs cured cutaneous wound healing and may provide a new therapeutic method for angiogenesis-related diseases.
Glycolysis promotes caspase-3 activation in lipid rafts in T cells
Authors: Secinaro Michael A. , Fortner Karen A. , Dienz Oliver , Logan Angela , Murphy Michael P. , Anathy Vikas , Boyson Jonathan E. , Budd Ralph C. 
Published: January 2018

AbstractResting T cells undergo a rapid metabolic shift to glycolysis upon activation in the presence of interleukin (IL)-2, in contrast to oxidative mitochondrial respiration with IL-15. Paralleling these different metabolic states are striking differences in susceptibility to restimulation-induced cell death (RICD); glycolytic effector T cells are highly sensitive to RICD, whereas non-glycolytic T cells are resistant. It is unclear whether the metabolic state of a T cell is linked to its susceptibility to RICD. Our findings reveal that IL-2-driven glycolysis promotes caspase-3 activity and increases sensitivity to RICD. Neither caspase-7, caspase-8, nor caspase-9 activity is affected by these metabolic differences. Inhibition of glycolysis with 2-deoxyglucose reduces caspase-3 activity as well as sensitivity to RICD. By contrast, IL-15-driven oxidative phosphorylation actively inhibits caspase-3 activity through its glutathionylation. We further observe active caspase-3 in the lipid rafts of glycolytic but not non-glycolytic T cells, suggesting a proximity-induced model of self-activation. Finally, we observe that effector T cells during influenza infection manifest higher levels of active caspase-3 than naive T cells. Collectively, our findings demonstrate that glycolysis drives caspase-3 activity and susceptibility to cell death in effector T cells independently of upstream caspases. Linking metabolism, caspase-3 activity, and cell death provides an intrinsic mechanism for T cells to limit the duration of effector function.
The silent healer: miR-205-5p up-regulation inhibits epithelial to mesenchymal transition in colon cancer cells by indirectly up-regulating E-cadherin expression
Authors: Gulei Diana , Magdo Lorand , Jurj Ancuta , Raduly Lajos , Cojocneanu-Petric Roxana , Moldovan Alin , Moldovan Cristian , Florea Adrian , Pasca Sergiu , Pop Laura-Ancuta , Moisoiu Vlad , Budisan Liviuta , Pop-Bica Cecilia , Ciocan Cristina , Buiga Rares , Muresan Mihai-Stefan , Stiufiuc Rares , Ionescu Calin , Berindan-Neagoe Ioana 
Published: January 2018

AbstractEMT represents the dominant program within advanced stages of colon cancer, where cells acquire migratory characteristics in order to invade secondary tissues and form metastasis. Where the majority of the therapeutic strategies are concentrated on the reduction of the tumor mass through different apoptotic mechanisms, the present study advocates an important role for miR-205-5p in impairment of colon cancer cells migration and restoration of the epithelial phenotype. Upon identification of a homogenous downregulated profile for miR-205-5p in colon adenocarcinoma patients, functional studies demonstrated that experimental upregulation of this sequence is able to significantly raise the levels of E-cadherin through direct inhibition of ZEB1. Moreover, the elevation in CDH1 expression was translated into functional parameters where cells lost their invasion and migratory characteristics and formed homogenous clusters through adhesion interactions. Survival analysis of colon adenocarcinoma patients revealed that low levels of miR-205-5p are associated with an unfavorable prognostic compared to those with increased expression, demonstrating the possible clinical utility of miR-205-5p replacement. Exogenous administration of miRNA mimics was not associated with significant changes in cell viability or inflammatory pathways. Therefore, the proposed strategy is aiming towards inhibition of metastasis and limitation of the tumor borders in advanced stages patients in order to prolong the survival time and to increase the efficiency of the current therapeutic strategies.
A global ocean atlas of eukaryotic genes
Authors: Carradec Quentin , Pelletier Eric , Da Silva Corinne , Alberti Adriana , Seeleuthner Yoann , Blanc-Mathieu Romain , Lima-Mendez Gipsi , Rocha Fabio , Tirichine Leila , Labadie Karine , Kirilovsky Amos , Bertrand Alexis , Engelen Stefan , Madoui Mohammed-Amin , Méheust Raphaël , Poulain Julie , Romac Sarah , Richter Daniel J. , Yoshikawa Genki , Dimier Céline , Kandels-Lewis Stefanie , Picheral Marc , Searson Sarah ,   Tara Oceans Coordinators, Acinas Silvia G. , Boss Emmanuel , Follows Michael , Gorsky Gabriel , Grimsley Nigel , Karp-Boss Lee , Krzic Uros , Pesant Stephane , Reynaud Emmanuel G. , Sardet Christian , Sieracki Mike , Speich Sabrina , Stemmann Lars , Velayoudon Didier , Weissenbach Jean , Jaillon Olivier , Aury Jean-Marc , Karsenti Eric , Sullivan Matthew B. , Sunagawa Shinichi , Bork Peer , Not Fabrice , Hingamp Pascal , Raes Jeroen , Guidi Lionel , Ogata Hiroyuki , de Vargas Colomban , Iudicone Daniele , Bowler Chris , Wincker Patrick 
Published: January 2018

AbstractWhile our knowledge about the roles of microbes and viruses in the ocean has increased tremendously due to recent advances in genomics and metagenomics, research on marine microbial eukaryotes and zooplankton has benefited much less from these new technologies because of their larger genomes, their enormous diversity, and largely unexplored physiologies. Here, we use a metatranscriptomics approach to capture expressed genes in open ocean Tara Oceans stations across four organismal size fractions. The individual sequence reads cluster into 116 million unigenes representing the largest reference collection of eukaryotic transcripts from any single biome. The catalog is used to unveil functions expressed by eukaryotic marine plankton, and to assess their functional biogeography. Almost half of the sequences have no similarity with known proteins, and a great number belong to new gene families with a restricted distribution in the ocean. Overall, the resource provides the foundations for exploring the roles of marine eukaryotes in ocean ecology and biogeochemistry.
Laser-accelerated particle beams for stress testing of materials
Authors: Barberio M. , Scisciò M. , Vallières S. , Cardelli F. , Chen S. N. , Famulari G. , Gangolf T. , Revet G. , Schiavi A. , Senzacqua M. , Antici P. 
Published: January 2018

AbstractLaser-driven particle acceleration, obtained by irradiation of a solid target using an ultra-intense (I > 1018 W/cm2) short-pulse (duration <1 ps) laser, is a growing field of interest, in particular for its manifold potential applications in different domains. Here, we provide experimental evidence that laser-generated particles, in particular protons, can be used for stress testing materials and are particularly suited for identifying materials to be used in harsh conditions. We show that these laser-generated protons can produce, in a very short time scale, a strong mechanical and thermal damage, that, given the short irradiation time, does not allow for recovery of the material. We confirm this by analyzing changes in the mechanical, optical, electrical, and morphological properties of five materials of interest to be used in harsh conditions.