bluuebunny/crossref_metadata_2025_split huggingface dataset:
The combination of a sphingosine kinase 2 inhibitor (ABC294640) and a Bcl‐2 inhibitor (ABT‐199) displays synergistic anti‐myeloma effects in myeloma cells without a t(11;14) translocation
Authors: Sundaramoorthy Pasupathi , Gasparetto Cristina , Kang Yubin 
Published: May 2018

AbstractMultiple myeloma (MM) remains an incurable disease in need of the development of novel therapeutic agents and drug combinations. ABT‐199 is a specific Bcl‐2 inhibitor in clinical trials for MM; however, its activity as a single agent was limited to myeloma patients with the t(11;14) translocation who acquire resistance due to co‐expression of Mcl‐1 and Bcl‐xL. These limitations preclude its use in a broader patient population. We have recently found that a sphingosine kinase 2‐specific inhibitor (ABC294640) induces apoptosis in primary human CD138+ cells and MM cell lines. ABC294640 is currently in phase I/II clinical trials for myeloma (clinicaltrials.gov: #NCT01410981). Interestingly, ABC294640 down‐regulates c‐Myc and Mcl‐1, but does not have any effects on Bcl‐2. We first evaluated the combinatorial anti‐myeloma effect of ABC294640 and ABT‐199 in vitro in 7 MM cell lines, all of which harbor no t(11;14) translocation. Combination index calculation demonstrated a synergistic anti‐myeloma effect of the combination of ABC294640 and ABT‐199. This synergistic anti‐myeloma effect was maintained even in the presence of bone marrow (BM) stromal cells. The combination of ABC294640 and ABT‐199 led to enhanced cleavage of PARP and caspase‐3/9 and increased Annexin‐V expression, consistent with the induction of apoptosis by the combination treatment. In addition, the combination of ABC294640 and ABT‐199 resulted in the down‐regulation of the anti‐apoptotic proteins Mcl‐1, Bcl‐2, and Bcl‐xL and the cleavage of Bax and Bid. The combination induced both the mitochondrial mediated‐ and caspase‐mediated apoptosis pathways. Finally, the combination of ABC294640 and ABT‐199 resulted in augmented anti‐myeloma effect in vivo in a mouse xenograft model. These findings demonstrate that the co‐administration of ABC294640 and ABT‐199 exhibits synergistic anti‐myeloma activity in vitro and in vivo, providing justification for a clinical study of this novel combination in patients with relapsed/refractory multiple myeloma.
Molecular features in young vs elderly breast cancer patients and the impacts on survival disparities by age at diagnosis
Authors: Wang Mei‐Xia , Ren Jun‐Ting , Tang Lu‐Ying , Ren Ze‐Fang 
Published: May 2018

AbstractYoung and elderly breast cancer patients are more likely to have a poorer outcome than middle‐aged patients. The intrinsic molecular features for this disparity are unclear. We obtained data from the Cancer Genome Atlas (TCGA) on May 15, 2017 to test the potential mediation effects of the molecular features on the association between age and prognosis with a four‐step approach. The relative contributions of the molecular features (PAM50 subtype, risk stratification, DNAm age, and mutations in TP53, PIK3CA, MLL3, CDH1, GATA3, and MAP3K1) to age disparities in survival were estimated by Cox proportional hazard models with or without the features. Young patients were significantly more likely to have basal‐like subtype, GATA3 mutations, and younger DNA methylation (DNAm) age than middle‐aged patients (P < .05). Both the young and elderly patients had a significantly increased risk of breast cancer recurrence after adjusted by race, tumor size, and node status (Hazard ratio [HR] (95% confidence interval [CI]): 2.81 [1.44, 5.45], 2.37 [1.45, 3.89], respectively). This increased risk was weakened in the young patients after further adjustments in the molecular features, particularly basal‐like subtype, GATA3 mutations, and DNAm age (HR [95%CI]: 1.87 [0.81, 4.32]), resulting in 33.5% decreased risk of recurrence. Meanwhile, the adjustments of the molecular features did not alter the recurrence risk for the elderly patients. Compared with middle‐aged patients of breast cancer, poorer prognosis of elderly patients may be caused by aging, while poorer prognosis of young patients was probably mediated through intrinsic characteristics, such as basal‐like subtype, GATA3 mutations, and DNAm age of the cancerous tissues.
Immediate breast reconstruction for women having inflammatory breast cancer in the United States
Authors: Patel Sameer A. , Ng Marilyn , Nardello Salvatore M. , Ruth Karen , Bleicher Richard J. 
Published: May 2018

AbstractInflammatory breast cancer (IBC) is an aggressive malignancy having a poor prognosis. Traditionally, reconstruction is not offered due to concerns about treatment delay, margin positivity, recurrence, and poor long‐term survival. There is a paucity of literature, however, evaluating whether immediate breast reconstruction (IBR) is associated with greater mortality in patients with IBC. A population‐based study was conducted via the SEER‐Medicare‐linked database (1991‐2009). Female patients greater than 65 years were reviewed who had mastectomy and reconstruction claims for nonmetastatic IBC. Competing risk and Cox regression were used to assess whether IBR was associated with higher breast cancer‐specific mortality (BCSM) or overall mortality (OM). Among 552 936 patients, 1472 (median age 74 years) were diagnosed with IBC and had a mastectomy. Forty‐four patients (3%) underwent IBR. Younger age, a lower Charlson comorbidity score, and a greater median income were predictors of IBR use. Tumor grade, hormone receptor status, and lymph node status were independent predictors of adjusted OM and BCSM. There was no difference by IBR status in BCSM or covariate‐adjusted BCSM (sHR 1.04; CI 0.71‐1.54; P = .83 and sHR 1.13; CI 0.84‐1.93; P = .58, respectively). Cumulative incidence of OM was lower among IR patients (P = .013), and IR did not influence the cumulative incidence of BCSM (P = .91). IBR was not associated with increased overall and BCSM mortality. Although further study of IBR in the IBC setting may be of value, these data suggest that IBC should not be considered an absolute contraindication to IBR.
Rituximab maintenance therapy of follicular lymphoma in clinical practice
Authors: Dührsen Ulrich , Broszeit‐Luft Stefanie , Dieing Annette , Lück Andreas , Porowski Piotr , Reiser Marcel , Schwinger Ulrike , Klawitter Sandra , Krumm Katja , Jentsch‐Ullrich Kathleen 
Published: May 2018

AbstractStandard of care for patients with symptomatic, advanced‐stage follicular lymphoma (FL) is rituximab‐containing chemoimmunotherapy followed by rituximab maintenance. This prospective, multicenter, noninterventional study analyzed how efficacy and safety data from randomized controlled trials translate into clinical practice in Germany. Both treatment‐naïve and relapsed/refractory patients with FL, who responded to rituximab‐containing induction and were scheduled for rituximab maintenance, were observed for 24 months. Effectiveness was measured by response and Kaplan‐Meier survival analysis. In addition, treatment patterns of induction and maintenance, as well as adverse events, were documented. The evaluable study population consisted of 310 first‐line patients and 173 relapsed/refractory patients, including 116 patients with initial Ann‐Arbor stage I/II and 20 patients with FL grade 3B. Regarding first‐line induction, a shift from R‐CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine, prednisone) to R‐bendamustine was observed over time, as well as a decline in radiotherapy. 2‐year progression‐free survival rates were 88.3% (95% confidence interval [CI] 84.0‐92.6) for first‐line patients and 76.0% (95% CI: 68.8‐83.3) for relapsed/refractory patients. Conversion from partial to complete remission (PR, CR) occurred in 53.4% of analyzed first‐line patients with PR, resulting in 69.4% CRs at study end (relapsed/refractory: conversion in 42.9%, final CRs 57.9%). Safety results were consistent with the known safety profile of rituximab in this setting. Both treatment‐naïve and relapsed/refractory patients with FL show favorable 2‐year PFS rates and improvements in the remission status with postinduction rituximab monotherapy as maintenance and consolidation therapy.
On the potential role of intestinal microbial community in hepatocarcinogenesis in chronic hepatitis B
Authors: Mohamadkhani Ashraf 
Published: May 2018

AbstractThe chronic infection of hepatitis B virus (HBV) is the most potent risk factor for the development of cirrhosis and hepatocellular carcinoma (HCC). The association of intestinal microbiota alteration with progressive liver disease has been investigated in recent studies. Overgrowth of potentially pathogenic bacteria of gram‐negative species and, in particular, a significant increase in the fecal count of Escherichia coli (E. coli) are characterized in the presence of HCC. This study was conducted to describe the characteristics of the intestinal microbiota related to the presence of HCC in HBV‐carrier patients. The available literature indicates the colonization of E. coli as principal source of portal vein lipopolysaccharide (LPS), in the gut may contribute to the carcinogenesis process by inducing chronic inflammation. This understanding could help to predict the clinical outcomes in HBV‐carrier patients and innovative strategies to reduce the virulence of liver disease from intestinal dysbiosis.
Colchicine, a microtubule‐disassembling drug, in the therapy of cardiovascular diseases
Authors: Chaldakov George N. 
Published: May 2018

AbstractColchicum autumnale, from which colchicine has been isolated more than 100 years ago, has been used as a treatment for pain and swelling for thousands of years. It is one of the few drugs known from that time period whose use has survived to modernity. Over the past decades, advances in the knowledge of (i) cytoskeletal microtubules (МТ), and (ii) anti‐inflammatory and anti‐fibrotic effects of colchicine, a classical MT‐disassembling (tubulin‐targeting) agent, have led to potential new uses for this very old drug extended beyond acute gouty arthritis and familial Mediterranean fever. Here, in brief, I present the Bulgarian contribution to possible potential of colchicine in the therapy of cardiovascular diseases that has emerged in the early 1970s in the Laboratory of Electron Microscopy, Medical Institute, Varna, Bulgaria, studying the secretory function of vascular smooth muscle cells. From this time onward, low‐dose colchicine (0.5–1.0 mg/daily) was increasingly administered orally for therapy of cardiovascular diseases such as acute coronary syndromes, postoperative atrial fibrillation (in cardiac surgery), pericarditis, cardiac hypertrophy‐associated heart failure, restenosis after angioplasty, and systemic necrotizing vasculitis. Thus, colchicine might be a new tool in the present therapeutic armamentarium for cardiovascular diseases. It is simply an example of MT‐disassembling drugs. Further studies will definitely be required before gaining real confidence in this kind of antitubulin pharmacology and therapy. This may lead to developing new and more specific antitubulins for cardiovascular diseases.
TRIM22 knockdown suppresses chronic myeloid leukemia via inhibiting PI3K/Akt/mTOR signaling pathway
Authors: Li Liyin , Qi Yanhua , Ma Xiaobo , Xiong Guosheng , Wang Lijun , Bao Cuixia 
Published: May 2018

AbstractTripartite motif‐containing 22 (TRIM22) is reported to participate in numerous cellular activities. Recent studies confirm that TRIM22 is a target gene for P53, and inhibits clonogenic growth of leukemic U‐937 cells. The current study aims to discover the effect of TRIM22 in progression of human chronic myeloid leukemia (CML) and explore the related mechanism. TRIM22 was knocked down by siRNA transfection in CML cell K562. We observed that TRIM22 knockdown decreased proliferation and invasion in K562 cells. TRIM22 knockdown significantly induced cell cycle arrest by regulating the level of CDK4, Cyclin D1, P70S6K, and P53 in K562 cell. Moreover, loss of TRIM22 also promoted apoptosis through modulation of Bcl‐2, Bax and active Caspase 3 in K562 cell. Furthermore, we demonstrated that TRIM22 knockdown inhibited the activation of PI3K/Akt/mTOR pathway by decreasing the level of the phosphorylated form p‐Akt and p‐mTOR in K562 cell. In conclusion, loss of TRIM22 suppresses the progression and invasion of CML through regulation of PI3K/Akt/mTOR pathway, suggesting that TRIM22 might be as a potential target for the treatment strategy of CML.
Polymeric Hollow‐Fiber Bundles as Immersed Heat Exchangers
Authors: Weiß Klarissa , Astrouski Ilya , Reppich Marcus , Raudenský Miroslav 
Published: May 2018

AbstractPlastic immersed heat exchangers are used in various applications where chemically neutral and noncorrosive equipment is required. Their potential competitors, namely, polymeric hollow‐fiber bundles, were investigated. Three different fiber bundles were tested as immersed coolers of a hot reservoir. Two types of polypropylene hollow fibers with various outside diameters were employed. Fibers were twisted with different curvature to achieve better distribution and improve natural convection on their outer surface. Calculation by experimental results was compared with the equation for natural convection across the horizontal cylinder, which overestimates heat transfer coefficients and can be applied for only rough estimation. Experimentally achieved pressure drops agreed well with theoretical prediction for laminar flow.
Towards Diastereomeric Pure Salts with Antisolvent Methods
Authors: Lőrincz László , Zsemberi Máté , Bánsághi György , Sohajda Tamás , Székely Edit 
Published: May 2018

AbstractChiral molecules, especially enantiomers and diastereomers of purity > 99 %, present a significant market share within the chemical, pharmaceutical, and flavor industries. Antisolvent precipitations, both batch and semicontinuous operations to serve the current trends in flow chemistry were demonstrated to be environmentally benign and efficient tools in achieving high optical purities. Although salts are known to be insoluble in supercritical CO2, instabilities of the nascent salts were detected and applied for increasing efficiency. Diastereomeric excess values of the crystalline products exceeded 99 % in maximum of three consecutive steps both by repeated resolution with half molar equivalent of the amine to the acid and by direct recrystallization of the salts.
Flow Properties of Drill Cuttings with Varying Drilling Fluid Content Using Jenike Shear Testing
Authors: Malagalage Anjana , Ratnayake Chandana , Saasen Arild , Thomassen Tonje , von Hafenbrädl Franz Otto 
Published: May 2018

AbstractDrill cuttings generated by offshore drilling operations are handled as a hazardous waste. In sensitive marine environments, the concept of zero discharge of waste is implemented. Hence, the drill cuttings have to be stored within the drilling rig for a short time period until they are transported to the onshore treatment facilities. As the drill cuttings are wet and sticky, conventional single silos may face the problem of blockage and rat holing. This preliminary study focuses on conducting flow property measurements. From the experiments the hopper angle and the required minimum outlet width were calculated. A plane symmetric silo with 25.8° hopper angle is suitable for all the conditions. The viscosity of the fluids is affecting the results significantly.
Understanding the Chemical Reactivity of Phosphonium‐Based Ionic Liquids with Tellurium
Authors: Zhang Tao , Schwedtmann Kai , Weigand Jan J. , Doert Thomas , Ruck Michael 
Published: May 2018

AbstractThe chemical reactivity of phosphonium based ionic liquids (ILs) towards tellurium at temperatures above 220 °C was systematically investigated by a series of dissolution experiments, tracking the solute tellurium species by nuclear magnetic resonance, and characterizing the reaction products by X‐ray diffraction and scanning electron microscopy. The initial step is the thermal elimination of an alkyl group of the phosphonium cation of the ILs, most probably via an SN2 mechanism. The addition of tellurium follows to form trialkylphosphane tellurides as evidenced by 31P and 125Te NMR spectroscopic experiments. The trialkylphosphane tellurides can serve as a tellurium reservoir for the formation of metal tellurides, like Bi2Te3 and Ag2Te. It was observed that trihexyltetradecylphosphonium chloride ([P6 6 6 14]Cl) shows a very weak reactivity that is reflected by a low solubility of tellurium, while trihexyltetradecylphosphonium dicyanamide/decanoate ([P6 6 6 14][N(CN)2]/[P6 6 6 14][decanoate]) and tetrabutylphosphonium decanoate ([P4 4 4 4][decanoate]) dissolve tellurium to a much higher extent. We attribute these observations to the different Lewis basicity of the anions of the ILs as main influencing factor.
Cationic Europium Complexes for Visualizing Fluctuations in Mitochondrial ATP Levels in Living Cells
Authors: Mailhot Romain , Traviss‐Pollard Thomas , Pal Robert , Butler Stephen J. 
Published: May 2018

AbstractThe ability to study cellular metabolism and enzymatic processes involving adenosine triphosphate (ATP) is impeded by the lack of imaging probes capable of signalling the concentration and distribution of intracellular ATP rapidly, with high sensitivity. We report here the first example of a luminescent lanthanide complex capable of visualizing changes in the concentration of ATP in the mitochondria of living cells. Four cationic europium(III) complexes [Eu.1–4]+ have been synthesized and their binding capabilities towards nucleoside polyphosphate anions examined in aqueous solution at physiological pH. Complexes [Eu.1]+ and [Eu.3]+ bearing hydrogen bond donor groups in the pendant arms showed excellent discrimination between ATP, ADP and monophosphate species. Complex [Eu.3]+ showed relatively strong binding to ATP (logKa=5.8), providing a rapid, long‐lived luminescent signal that enabled its detection in a highly competitive aqueous medium containing biologically relevant concentrations of Mg2+, ADP, GTP, UTP and human serum albumin. This EuIII complex responds linearly to ATP within the physiological concentration range (1–5 mm), and was used to continuously monitor the apyrase‐catalyzed hydrolysis of ATP to ADP in vitro. We demonstrate that [Eu.3]+ can permeate mammalian (NIH‐3T3) cells efficiently and localize to the mitochondria selectively, permitting real‐time visualization of elevated mitochondrial ATP levels following treatment with a broad spectrum kinase inhibitor, staurosporine, as well as depleted ATP levels upon treatment with potassium cyanide under glucose starvation conditions.
Electronic Interactions in Illuminated Carbon Dot/MoS2 Ensembles and Electrocatalytic Activity towards Hydrogen Evolution
Authors: Canton‐Vitoria Ruben , Vallan Lorenzo , Urriolabeitia Esteban , Benito Ana M. , Maser Wolfgang K. , Tagmatarchis Nikos 
Published: May 2018

AbstractThe preparation, characterization, and photophysical and electrocatalytic properties of carbon dot (CD)/MoS2 ensembles is reported. Based on electrostatic interactions, ammonium‐functionalized MoS2, which was prepared upon reaction of 1,2‐dithiolane tert‐butyl carbamate with MoS2 followed by acidic deprotection, was coupled with CDs bearing multiple carboxylates on their periphery, as derived upon microwave‐assisted polycondensation of citric acid and ethylenediamine followed by alkaline treatment. Insights into electronic interactions between the two species within CD/MoS2 ensembles emanated from absorption and photoluminescence titration assays. Efficient fluorescence quenching of CDs by MoS2 was observed and attributed to photoinduced electron/energy transfer as the decay mechanism for the transduction of the singlet excited state of CDs. Finally, the electrocatalytic performance of the CD/MoS2 ensemble was assessed towards the hydrogen evolution reaction and found to be superior to that of individual CDs species.
Supramolecular Interactions of Fullerene C60 with 1,3,5‐Trifluoro‐2,4,6‐triiodobenzene: A Combined Theoretical and Experimental Study
Authors: Zhang Yu , Wang Jian‐Ge , Sun Xiaotian , Liu Qiaohong , Wang Weizhou , Wang Yi‐Bo 
Published: May 2018

AbstractThe noncovalent interactions between fullerene C60 and 1,3,5‐trifluoro‐2,4,6‐triiodobenzene (C6F3I3) have been investigated in detail by means of a combined theoretical and experimental study. The noncovalent interactions formed by C60 with C6F3I3 in the gas phase were modeled by means of quantum chemical calculations, and the noncovalent interactions formed between C60 and C6F3I3 in the solid state were explored by means of single‐crystal X‐ray diffraction studies at both low temperature and room temperature. In both the gas phase and solid state, formations of the π⋅⋅⋅π‐stacking interactions, halogen bonds, and F⋅⋅⋅π interactions were found in the supramolecular complexes of C60 with C6F3I3. The strength of these noncovalent interactions was characterized by means of dispersion‐corrected density functional theory (DFT) calculations, and the nature of these noncovalent interactions was revealed through energy‐component analyses.
Ruthenium Supported on High‐Surface‐Area Zirconia as an Efficient Catalyst for the Base‐Free Oxidation of 5‐Hydroxymethylfurfural to 2,5‐Furandicarboxylic Acid
Authors: Pichler Christian M. , Al‐Shaal Mohammad G. , Gu Dong , Joshi Hrishikesh , Ciptonugroho Wirawan , Schüth Ferdi 
Published: May 2018

AbstractSeveral ZrO2‐supported ruthenium catalysts were prepared and utilized in the oxidation of 5‐hydroxymethylfurfural (HMF) to 2,5‐furandicarboxylic acid (FDCA) under base‐free conditions. Full conversion of HMF and almost perfect selectivity towards FDCA (97 %) were achieved after 16 h by using pure O2 as an oxidant and water as a solvent. The catalytic tests show that the size of the Ru particles is crucial for the catalytic performance and that the utilization of high‐surface‐area ZrO2 leads to formation of very small Ru particles. Superior activity was obtained for catalysts based on ZrO2 that had been synthesized by a surface‐casting method and has high surface areas up to 256 m2 g−1. In addition to good activity and selectivity, these catalysts show also high stability and constant activity upon recycling, confirming the suitability of Ru/ZrO2 in the base‐free oxidation of HMF.
Utilizing Waste Thermocol Sheets and Rusted Iron Wires to Fabricate Carbon–Fe3O4 Nanocomposite‐Based Supercapacitors: Turning Wastes into Value‐Added Materials
Authors: Vadiyar Madagonda M. , Liu Xudong , Ye Zhibin 
Published: May 2018

AbstractThe synthesis of porous activated carbon (specific surface area=1883 m2 g−1), Fe3O4 nanoparticles, and carbon–Fe3O4 (C−Fe3O4) nanocomposites from local waste thermocol sheets and rusted iron wires is demonstrated herein. The resulting carbon, Fe3O4 nanoparticles, and C−Fe3O4 composites are used as electrode materials for supercapacitor applications. In particular, C−Fe3O4 composite electrodes exhibit a high specific capacitance of 1375 F g−1 at 1 A g−1 and longer cyclic stability with 98 % capacitance retention over 10 000 cycles. Subsequently, an asymmetric supercapacitor, namely, C−Fe3O4∥Ni(OH)2/carbon nanotube device, exhibits a high energy density of 91.1 Wh kg−1 and a remarkable cyclic stability, with 98 % capacitance retention over 10 000 cycles. Thus, this work has important implications not only for the fabrication of low‐cost electrodes for high‐performance supercapacitors, but also for the recycling of waste thermocol sheets and rusted iron wires for value‐added reuse.