bluuebunny/crossref_metadata_2025_split huggingface dataset:
A real-world comparative analysis of carfilzomib and other systemic multiple myeloma chemotherapies in a US community oncology setting
Authors: Rifkin Robert M. , Medhekar Rohan , Amirian E. Susan , Aguilar Kathleen M. , Wilson Thomas , Boyd Marley , Mezzi Khalid , Panjabi Sumeet 
Published: January 2019

Background: Most multiple myeloma (MM) patients ultimately progress, with remission duration decreasing after first relapse. Recently, novel agents have been approved for the treatment of relapsed MM. There is a paucity of real-world data on these treatments. We sought to compare time to next treatment (TTNT) in MM patients in their second line of therapy (LOT2), treated with common proteasome inhibitor (PI)-based triplets. Methods: Adult MM patients who received carfilzomib (K) between 1 November 2013 and 29 February 2016 at US Oncology Network (USON) clinics utilizing iKnowMed™ electronic health records (EHRs) were identified. Patients were included if they were ⩾18 years of age, not enrolled in clinical trials, had ⩾2 visits at a USON clinic and received LOT2 regimens consisting of: K+lenalidomide with steroid (KRd), bortezomib+lenalidomide with steroid (VRd), or bortezomib+cyclophosphamide with steroid (VCyd). TTNT was estimated from LOT2 initiation to LOT3 initiation using the Kaplan–Meier method, and hazard ratios (HRs) were estimated using Cox modeling. Results: A total of 718 patients received a K-containing regimen sometime during their MM treatment (LOT1 to LOT5). Of these, 156 patients received: KRd ( n = 112; 71.8%), VRd ( n =27; 17.3%), or VCyd ( n = 17; 10.9%). Baseline characteristics were similar between groups (mean age: 64.8 years; 58% male). Median TTNT was longest for KRd [25.3 months; 95% confidence interval (CI): 19.71–NR], versus VRd or VCyd (VRd median TTNT: 10.2 months, 95% CI: 4.24–12.71; VCyd: 6.5 months, 95% CI: 3.02–12.78; log-rank p < 0.0001). The adjusted HR for KRd was 0.19 (95% CI: 0.11–0.37), compared with VRd. Conclusions: Considering the real-world nature of these data, the median TTNT observed with KRd was relatively consistent, with progression-free survival (PFS) for KRd observed in the phase III ASPIRE trial (median PFS: ITT population = 26.3 months; LOT2 = 29.6 months). Patients who received KRd at first relapse had significantly longer TTNT, compared with those on VRd or VCyd, confirming the value of KRd as an important treatment option for relapsed MM.
Follistatin-like 1 protects mesenchymal stem cells from hypoxic damage and enhances their therapeutic efficacy in a mouse myocardial infarction model
Authors: Shen Han , Cui Guanghao , Li Yanqiong , Ye Wenxue , Sun Yimin , Zhang Zihan , Li Jingjing , Xu Guiying , Zeng Xiansheng , Zhang Yanxia , Zhang Wencheng , Huang Zan , Chen Weiqian , Shen Zhenya 
Published: January 2019

Abstract
Background
Cell therapy remains the most promising approach against ischemic heart injury. However, poor survival of engrafted cells in ischemic sites diminishes its therapeutic efficacy. Follistatin-like 1 (Fstl1) is documented as a novel pro-survival cardiokine for cardiomyocytes, and it is protective during ischemic heart injury. In the present study, we characterize the potential of Fstl1 as an effective strategy to enhance hypoxia resistance of donor cells and optimize stem cell-based therapy.

Methods
Murine bone marrow-derived mesenchymal stem cells (MSCs) were expanded in monolayer culture and characterized by flow cytometry. MSCs were subjected to hypoxia to mimic cardiac ischemic environment. Expression of Fstl1 was monitored 0, 24, and 48 h following hypoxia. Constitutive expression of Fstl1 in MSCs was achieved by lentivirus-mediated Fstl1 overexpression. Genetically modified MSCs were further collected for cell death and proliferation assay following 48 h of hypoxic treatment. Acute myocardial infarction (MI) model was created by ligating the left anterior descending coronary artery, while control MSCs (MSCs-mCherry) or Fstl1-overexpressing MSCs (MSCs-Fstl1) were injected into the peri-infarct zone simultaneously. Subsequently, retention of the donor cells was evaluated on post-therapy 1, 3, & 7 days. Finally, myocardial function, infarct size, inflammation, and neovascularization of the infarcted hearts were calculated thereafter.

Results
Expression of Fstl1 in hypoxic MSCs declines dramatically in a time-dependent manner. In vitro study further demonstrated that Fstl1 promotes survival and proliferation of hypoxic MSCs. Moreover, Fstl1 significantly prolongs MSC survival/retention after implantation. Finally, transplantation with Fstl1-overexpressing MSCs significantly improves post-MI cardiac function by limiting scar formation, reducing inflammatory response, and enhancing neovascularization.

Conclusions
Our results suggest Fstl1 is an intrinsic cardiokine promoting survival and proliferation of MSCs, thereby optimizing their engraftment and therapeutic efficacy during cell therapy.
An integrated characterization of contractile, electrophysiological, and structural cardiotoxicity of Sophora tonkinensis Gapnep. in human pluripotent stem cell-derived cardiomyocytes
Authors: Wang Ruiying , Wang Min , Wang Shan , Yang Ke , Zhou Ping , Xie Xueheng , Cheng Qi , Ye Jingxue , Sun Guibo , Sun Xiaobo 
Published: January 2019

Abstract
Background
Cardiotoxicity remains an important concern in drug discovery and clinical medication. Meanwhile, Sophora tonkinensis Gapnep. (S. tonkinensis) held great value in the clinical application of traditional Chinese medicine, but cardiotoxic effects were reported, with matrine, oxymatrine, cytisine, and sophocarpine being the primary toxic components.

Methods
In this study, impedance and extracellular field potential (EFP) of human-induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) were recorded using the cardio non-labeled cell function analysis and culture system (Cardio-NLCS). The effects of matrine, oxymatrine, cytisine, and sophocarpine (2, 10, 50 μM) on cell viability; level of lactate dehydrogenase (LDH), creatine kinase MB isoenzyme (CK-MB), and cardiac troponin I (CTn-I); antioxidant activities; production of reactive oxygen species (ROS) and malondialdehyde (MDA); and disruption of intracellular calcium homeostasis were also added into the integrated assessment.

Results
The results showed that matrine and sophocarpine dose-dependently affected both impedance and EFP, while oxymatrine and cytisine altered impedance significantly. Our study also indicated that cardiotoxicity of matrine, oxymatrine, cytisine, and sophocarpine was related to the disruption of calcium homeostasis and oxidative stress. Four alkaloids of S. tonkinensis showed significant cardiotoxicity with dose dependence and structural cardiotoxicity synchronized with functional changes of cardiomyocytes.

Conclusions
This finding may provide guidance for clinical meditation management. Furthermore, this study introduced an efficient and reliable approach, which offers alternative options for evaluating the cardiotoxicity of the listed drugs and novel drug candidates.
Understanding divergence of living standards between Asia and Europe: a proposition of regionally dominant cultural effects
Authors: Yong Enn Lun 
Published: January 2019

AbstractThis paper aims to compare living standards in Asia and in Europe with respect to several cultural dimensions to which the research on economic prosperity has paid attention. Some studies pool countries in multiple regions to identify cultural effects on economic prosperity, and this paper argues that such regional differences in culture must be considered. In addition to empirically distinguishing Asia and Europe in terms of living standards with respect to selected cultural dimensions, this study also distinguishes and investigates regions within Europe. A theoretical argument explains each region’s dominant cultural dimension, thereby hypothesizing regionally distinct effects of culture on living standards. A quadruple model is developed, and different samples are used to test the reliability and validity of the theoretical proposition. Two cultural dimensions, individualism and power distance, are identified as hallmarks of the divergence of living standards between Asia and Europe. Individualism has a significantly positive effect in Europe but insignificant in Asia, whereas the findings are opposite for power distance. The results remain robust even after controlling for confounders. The findings suggest potential barriers to maximizing the effectiveness of economic policies because a development approach adopted from Europe could be less effective in Asia, and vice versa, owing to a different dominant culture.
SOD1 activity threshold and TOR signalling modulate VAP(P58S) aggregation via ROS-induced proteasomal degradation in aDrosophilamodel of Amyotrophic Lateral Sclerosis
Authors: Chaplot Kriti , Pimpale Lokesh , Ramalingam Balaji , Deivasigamani Senthilkumar , Kamat Siddhesh S. , Ratnaparkhi Girish S. 
Published: January 2019

Familial Amyotrophic Lateral Sclerosis (F-ALS) is an incurable, late onset motor neuron disease, linked strongly to various causative genetic loci. ALS8 codes for a missense mutation, P56S, in VAMP-associated Protein B (VAPB) that causes the protein to misfold and form cellular aggregates. Uncovering genes and mechanisms that affect aggregation dynamics would greatly help increase our understanding of the disease and lead to potential therapeutics.We developed a quantitative high-throughput, Drosophila S2R+ cell-based kinetic assay coupled with fluorescent microscopy to score for genes involved in the modulation of aggregates of fly ortholog, VAP(P58S), fused with GFP. A targeted RNAi screen against 900 genes identified 150 hits that modify aggregation, including the ALS loci SOD1, TDP43 and also genes belonging to the TOR pathway. Further, a system to measure the extent of VAP(P58S) aggregation in the Drosophila larval brain was developed in order to validate the hits from the cell based screen. In the larval brain, we find that reduction of SOD1 level or decreased TOR signalling reduces aggregation, presumably by increasing levels of cellular reactive oxygen species (ROS). The mechanism of aggregate clearance is, primarily, proteasomal degradation which appears to be triggered by an increase in ROS.We have thus uncovered an interesting interplay between SOD1, ROS and TOR signalling that regulates the dynamics of VAP aggregation. Mechanistic processes underlying such cellular regulatory networks will lead us to a better understanding of initiation and progression of ALS.
Exocyst subunit Sec6 is positioned by microtubule overlaps in the moss phragmoplast prior to cell plate membrane arrival
Authors: Tang Han , de Keijzer Jeroen , Overdijk Elysa J. R. , Sweep Els , Steentjes Maikel , Vermeer Joop E. M. , Janson Marcel E. , Ketelaar Tijs 
Published: January 2019

ABSTRACT
During plant cytokinesis a radially expanding membrane-enclosed cell plate is formed from fusing vesicles that compartmentalizes the cell in two. How fusion is spatially restricted to the site of cell plate formation is unknown. Aggregation of cell-plate membrane starts near regions of microtubule overlap within the bipolar phragmoplast apparatus of the moss Physcomitrella patens. Since vesicle fusion generally requires coordination of vesicle tethering and subsequent fusion activity, we analyzed the subcellular localization of several subunits of the exocyst, a tethering complex active during plant cytokinesis. We found that the exocyst complex subunit Sec6 but not the Sec3 or Sec5 subunits localized to microtubule overlap regions in advance of cell plate construction in moss. Moreover, Sec6 exhibited a conserved physical interaction with an ortholog of the Sec1/Munc18 protein KEULE, an important regulator for cell-plate membrane vesicle fusion in Arabidopsis. Recruitment of the P. patens protein KEULE and vesicles to the early cell plate was delayed upon Sec6 gene silencing. Our findings, thus, suggest that vesicle-vesicle fusion is, in part, enabled by a pool of exocyst subunits at microtubule overlaps, which is recruited independently of vesicle delivery.
From Heroic Durga to the Next Victim of an Oppressive Patriarchal Indian Culture: Too Many Variants of Phoolan Devi’s Biography
Authors: Szurlej Tatiana 
Published: January 2019

Phoolan Devi (10.08.1963–25.07.2001), the famous Bandit Queen still appears in stories about famous Indian women. However, while in India, mainly among poor villagers, she is usually described as a heroic defender of the poorest, in the West Phoolan is seen primarily as another victim of Indian patriarchal culture. Moreover, although most of books about Phoolan are based on interviews with her, every version of her biography differs from one another, which raises the question whether these differences are the consequence of a conscious manipulation of a person who tries to justify certain dark aspects of her life, since the famous dacoit owes her fame to her bloody act of revenge on Thakurs in the Behmai village, which was the biggest crime committed by bandits in India until then.
The most popular story about Phoolan’s life is the film Bandit Queen made in 1994 by Shekhar Kapur, based on the book India’s Bandit Queen. The True Story of Phoolan Devi by Mala Sen, who is also the author of the screenplay. The autobiography of Phoolan Devi, who tried to stop the release of the Bandit Queen, claiming that it shows a false story, was written in response to those two works. By constructing her image in the autobiography, Phoolan Devi tries to appear as a very strong woman who could achieve a lot, in spite of adverse conditions. Yet it is hard to resist the impression that the autobiography of Phoolan Devi, despite of its very realistic elements, is to some extent a false testimony. The question remains whether it was the publisher, who decided to construct the story this way to satisfy the tastes of the Western readers and respond to their needs, just like the movie of Shekhar Kapur, or maybe Phoolan, deliberately or unknowingly, presented herself as a victim in search of sympathy after the massacre in Behmai.
Building strong health supply chain systems: the visibility and analytics network approach to improving the Nigeria immunisation supply chain
Authors: Ottih Chibuzo , Cussen Kevin , Mustafa Mahmud 
Published: January 2019

BackgroundHealth supply chain managers are unable to effectively monitor the performance of the immunisation supply chain in Nigeria. As a result, they are unable to make effective, data-driven decisions. This results in poor vaccine availability at some service delivery points. A lack of reliable data for evidence-based decision making is a significant contributor to this challenge.MethodThe visibility and analytics network (VAN) principles were introduced to enable end-to-end visibility in the immunisation supply chain and logistics (ISCL) system and make more accurate data available to health supply chain managers.ResultsThe application of the VAN principles has led to improved data collection, real-time stock visibility and enhanced data analytics framework. This enhanced visibility has promoted a culture of accountability and data-driven decision-making, previously unattainable. Health supply chain managers are now equipped with better skills and tools to promote effective operation of the immunisation supply chain.ConclusionThe introduction of VAN principles has been an effective approach to improving data visibility and creating incremental improvements in the ISCL in Nigeria.
Lead-silver anode behavior for zinc electrowinning in sulfuric acid solution
Authors: Zhang Wei , Haskouri Sanae , Houlachi Georges , Ghali Edward 
Published: January 2019

Abstract
In recent years, a renewed interest in studying the electrochemical corrosion behavior of lead anodes during zinc electrowinning is probably due to the particularly high sulfuric acid concentrations in zinc electrolyte where lead alloy anodes have high cell voltage and high corrosion rate of lead. The high corrosion rate of lead alloy resulted in Pb contamination on zinc deposit. In zinc electrometallurgy, the electrolyte from a zinc-rich ore contains a significant amount of Mn2+. Mn2+ in the zinc electrolyte results in forming an oxide film on lead anodes during electrolysis. Pb-0.7% Ag anode is generally used in the zinc industry. To improve the technical performance and decrease product cost, other anodes, such as Pb-Ca or Pb-Ag-Ca or Pb-Ag-Ti or Pb-Ag-Se alloys were tested. Till now, none of them has succeeded in the substitution of Pb-Ag anodes in the zinc electrowinning. As an alloying element, silver in small quantities is considered because of the benefits that generates on the anode during electrolysis. During zinc electrolysis, lead dissolution into the zinc electrolyte can be harmful to the quality of zinc deposit. However, the lead silver alloy anode can decrease the lead content in the zinc deposit by pre-treated methods such as blasting and preconditioning.
Simulation of cement raw material deposits using plurigaussian technique
Authors: Yünsel Tayfun Yusuf 
Published: January 2019

Abstract
Plurigaussian simulation is a powerful and very effective technique for modelling subsurface rock type domain distribution and in-situ mining reserve analysis. Modelling of subsurface to reveal the rock type distribution plays a key role for raw material extraction planning and plant operations such as extraction, transportation and comminution strategies. Because, the raw material distribution defines the plant operations and final product quality (cement modulus). This study addresses the application of plurigaussian simulation technique to reveal the subsurface rock type distribution of a cement raw material deposit in Turkey. The rock type domains include the limestone, clayey limestone, marl and sandstone which are the basic four rock type classes effecting the cement modulus in the field. The simulation process is carried out using these four rock type data on a determined grid system. A series of tests are made for the validation of the plurigaussian simulation. As a result, the rock type distributions are presented as both 2D-3D graphics and tabulated. The limestone is found as a dominant rock type in the deposit. The marl – a natural clinker - is another widespread raw material in the field and is found interbedded with limestone across the study field. The unwanted sandstone existence exhibited a sparse distribution in reserve body. The results indicated that, the deposit can provide the required raw material for the plant, showing the localised rock type distribution. A detailed raw material extraction planning and scheduling may be made using the results of this study.
Application of the nanoindentation technique for the characterization of varved clay
Authors: Tankiewicz Matylda 
Published: January 2019

AbstractNanoindentation is a test carried out in a small scale, during which a rigid indenter (of known hardness and geometry) is pressed into the tested material. The results of the test are the load and unload curves, from which the harerial characterized by high heterogeneity (like soil – composed of grains and particles of different size and mineral composition), the use of multiple nanoindentation on a predefined grid (Grid Indentation Technique) is reasonable. It allows for the determination of the morphology of the material in a selected scale of observation. In the study, nanoindetation tests were performed on samples of varved clay - soil composed of two alternately arranged layers - occurring near the city of Bełchatów in central Poland. Due to the layered structure of the material, the tests were carried out for both layers separately. The outcomes show that there are significant differences in the values of their mechanical properties. Application of the deconvolution technique also allowed for the estimation of the number of components of both layers and their mechanical properties.
Effect of hardening parameters of wood preservatives based on tannin copolymers
Authors: Sommerauer Lukas , Thevenon Marie-France , Petutschnigg Alexander , Tondi Gianluca 
Published: January 2019

AbstractAmongst polyphenols, tannins belong to the most effective chemical protection systems against biological attack on trees. Tannins are water-soluble and are thus leached out easily when used for wood protection.In situpolymerized tannin-hexamine wood preservatives have better leaching resistance (LR), but they do not resist weathering. In this study, tannin copolymer formulations were prepared with hexamine, formaldehyde, furfural, glyoxal, furfuryl alcohol and maleic anhydride, impregnated in wood, and cured at higher temperatures. The wood samples treated with these formulations were tested for their anti-swelling efficiency (ASE), leaching behavior, mechanical properties, and their resistance against fire, weathering and biological attack. Several tannin-treated specimens showed improved hardness and enhanced leaching and fire resistance. Some formulations also responded well to artificial weathering cycles, but natural weathering cycles deteriorated their performance. Samples treated with maleic anhydride showed improved leachability and high biological resistances, even without the addition of inorganic biocides. These organic and bio-friendly products can be considered as promising alternatives to heavy metal-based wood preservatives.
Antonym adjective pairs and prosodic iconicity: evidence from letter replications in an English blogger corpus
Authors: Fuchs Susanne , Savin Egor , Solt Stephanie , Ebert Cornelia , Krifka Manfred 
Published: January 2019

AbstractWhile the general assumption has long been that natural languages exhibit an arbitrary pairing of form and meaning, there is increasing empirical evidence that iconicity in language is not uncommon. One example from spoken language involves iconic prosodic modulation, i.e. the changing of prosodic features such as duration and fundamental frequency to express meanings such as size and speed. In this paper, we use data from an English social media corpus, with 140 million words written by 19,320 bloggers, to investigate a counterpart to iconic prosodic modulation in written language, namely letter replications (e.g.loooong). We examine pairs of gradable adjectives such asshort/long,tiny/hugeandfast/slow, finding a higher frequency of letter replications for adjectives associated with greater size or spatial/temporal extent. We did not find an iconic effect on the number of replicated letters. Our results show evidence for iconic prosody in written language, and further demonstrate that social media databases offer an excellent opportunity to investigate naturalistic written language.
On a conjecture about generalized Q-recurrence
Authors: Alkan Altug 
Published: January 2019

AbstractChaotic meta-Fibonacci sequences which are generated by intriguing examples of nonlinear recurrences still keep their mystery although substantial progress has been made in terms of well-behaved solutions of nested recurrences. In this study, a recent generalization of Hofstadter’s famous Q-sequence is studied beyond the known methods of generational approaches in order to propose a generalized conjecture regarding the existence of infinitely many different solutions for all corresponding recurrences of this generalization.