bluuebunny/crossref_metadata_2025_split huggingface dataset:
Phase II clinical trial of pazopanib for patients with unresectable or metastatic malignant peripheral nerve sheath tumors
Authors: Nishida Yoshihiro , Urakawa Hiroshi , Nakayama Robert , Kobayashi Eisuke , Ozaki Toshifumi , Ae Keisuke , Matsumoto Yoshihiro , Tsuchiya Hiroyuki , Goto Takahiro , Hiraga Hiroaki , Naka Norifumi , Takahashi Shunji , Ando Yuichi , Ando Masahiko , Kuwatsuka Yachiyo , Hamada Shunsuke , Ueda Takafumi , Kawai Akira 
Published: July 2020

AbstractMalignant peripheral nerve sheath tumor (MPNST) often does not respond well to chemotherapy and develops against a background of NF1. The purpose of our study was to examine the efficacy of pazopanib against MPNST. Our study was designed as a physician‐initiated phase II clinical trial in patients with advanced MPNST. Patients were registered from 11 large hospitals. The primary endpoint was set to clarify the clinical benefit rate (CBR) at 12 weeks according to response evaluation criteria in solid tumors (RECIST). Progression‐free survival (PFS), overall survival (OS) and the CBR based on modified Choi evaluation at week 12 were set as secondary endpoints along with treatment‐related safety. The study enrolled 12 patients. Median age was 49 years. Seven had Grade 2 and five Grade 3 according to the FNCLCC evaluation. Median follow‐up period was 10.6 months. CBR at 12 weeks was both 50.0% (RECIST and Choi). The median PFS was 5.4 months for both RECIST and Choi, and the median OS was 10.6 months. Of special interest, the median PFS was 2.9 months for patients with FNCLCC Grade 2 and 10.2 months for Grade 3 (both RECIST and Choi). Grade 4 adverse events of neutropenia and lipase elevation were noted in one patient each. The results of this pazopanib therapy were generally better than those of any of the other single molecular targeted therapies reported previously. Although accumulation of more cases remains necessary, we conclude pazopanib treatment for MPNST to be a safe and promising treatment after doxorubicin‐based chemotherapy.
The impact of SAMHD1 expression and mutation status in mantle cell lymphoma: An analysis of the MCL Younger and Elderly trial
Authors: Roider Tobias , Wang Xi , Hüttl Katrin , Müller‐Tidow Carsten , Klapper Wolfram , Rosenwald Andreas , Stewart James Peter , de Castro David Gonzalez , Dreger Peter , Hermine Olivier , Kluin‐Nelemans Hanneke C. , Grabe Niels , Dreyling Martin , Pott Christiane , Ott German , Hoster Eva , Dietrich Sascha 
Published: July 2020

AbstractThe sterile alpha motif and histidine‐aspartic domain‐containing protein 1 (SAMHD1) has been demonstrated to predict the response to high‐dose cytarabine consolidation treatment in acute myeloid leukemia patients. Here, we evaluated SAMHD1 as potential biomarker for the response to high‐dose cytarabine in mantle cell lymphoma (MCL) patients. We quantified SAMHD1 protein expression and determined the mutation status in patients of the MCL Younger and Elderly trials (n = 189), who had received high‐dose cytarabine‐ or fludarabine‐based polychemotherapy. Additionally, we quantified SAMHD1 expression in B cell lymphoma cell lines and exposed them to cytarabine, fludarabine, and clinically relevant combinations. Across both trials investigated, SAMHD1 mutations had a frequency of 7.1% (n = 13) and did not significantly affect the failure‐free survival (FFS, P = .47). In patients treated with high‐dose cytarabine‐ or fludarabine‐containing regimes, SAMHD1 expression was not significantly associated with FFS or complete remission rate. SAMHD1 expression in B cell lymphoma cell lines, however, inversely correlated with their in vitro response to cytarabine as single agent (R = .65, P = .0065). This correlation could be reversed by combining cytarabine with other chemotherapeutics, such as oxaliplatin and vincristine, similar to the treatment regime of the MCL Younger trial. We conclude that this might explain why we did not observe a significant association between SAMHD1 protein expression and the outcome of MCL patients upon cytarabine‐based treatment.
SIRT1‐mediated amelioration of oxidative stress in kidney of alcohol‐aflatoxin‐B1‐induced hepatocellular carcinoma by resveratrol is catalase dependent and GPx independent
Authors: Rawat Divya , Shrivastava Somi , Naik Rayees Ahmad , Chhonker Saurabh Kumar , Koiri Raj Kumar 
Published: July 2020

AbstractHepatocellular carcinoma (HCC) is a type of primary liver cancer and dietary exposure to aflatoxins is a major risk factor of HCC. The current study aimed to assess the role of resveratrol and nicotinamide in renal toxicity during alcohol‐aflatoxin‐B1‐induced HCC. The results revealed that resveratrol treatment normalized the level of urea, lipid peroxidation, lactate and lactate dehydrogenase, which were increased in HCC. It also downregulated the increased expression of sirtuin 1 in HCC kidney. Furthermore, amelioration of oxidative stress in kidney of HCC rats by resveratrol was observed to be catalase dependent and glutathione peroxidase independent.
Comparison of the Effects of Low‐Molecular‐Weight Heparin and Fondaparinux on Liver Function in Patients With Pulmonary Embolism
Authors: Yang Xu , Li Nan , Guo Tingting , Guan Xiaoyuan , Tan Jiangshan , Gao Xin , Wu Yan , Jia Lei , Gu Min , Hua Lu , Liu Hong 
Published: July 2020

AbstractHepatotoxicity with low‐molecular‐weight heparin (LMWH) or fondaparinux is a relatively common adverse reaction. This study assessed the effects of LMWH and fondaparinux on liver function in patients with pulmonary embolism based on a retrospective cohort. As a result, a total of 463 patients with pulmonary embolism and treated with LMWH (enoxaparin sodium or nadroparin calcium) or fondaparinux sodium were included. Liver dysfunction was identified in 79 patients (17.1%), of whom 97.5% had grade 1 drug‐induced liver injury (DILI) and 2.5% had grade 2 DILI. The results showed that liver dysfunction usually occurred in the first week after anticoagulant administration, and the liver tests of all patients with liver dysfunction gradually recovered or alleviated at discharge. The multivariable logistic regression analysis indicated that a longer treatment course and hepatitis B surface antigen‐positive (HBsAg+) were risk factors for liver dysfunction (P < .05). Moreover, nadroparin calcium had the highest risk of liver dysfunction, approximately 2.2 times (95% confidence interval [CI], 1.1740‐4.224; P = .015) that of enoxaparin sodium. In conclusion, nearly one‐fifth and 10% of patients prescribed with LMWH or fondaparinux, respectively, for pulmonary embolism had liver dysfunction, mainly with mild liver injury and characterized by self‐limited elevated serum transaminase levels. Hence, during the 3 anticoagulant applications, we should pay more attention to the monitoring of liver function in the first week and transit to oral anticoagulants if possible, especially for patients who are HBsAg+ or suffering from other liver diseases.
An investigation of the role of spatial ability in representing and solving word problems among engineering students
Authors: Duffy Gavin , Sorby Sheryl , Bowe Brian 
Published: July 2020

AbstractBackgroundSpatial ability is significantly related to performance in engineering education, and problem‐solving, an activity that is highly relevant to engineering education, has been linked to spatial ability.Purpose/HypothesisThis study investigated the following question: To what extent is spatial ability related to problem‐solving among engineering students and how do approaches to problem representation and solution vary with spatial ability level?Design/MethodA spatial ability test, a set of math word problems and an accompanying math ability test, was administered to two samples of first‐year engineering students in two countries. Data were analyzed at the test level to evaluate the relationship of spatial ability to problem representation and solution. A detailed item level analysis was conducted to compare approach to problem‐solving with spatial ability level.ResultsSpatial ability was found to be significantly related to problem‐solving but not to the math ability test, indicating the relationship was limited to the problem representation phase, not the solution phase. Key aspects of representation were identified for each problem to reveal a more pronounced relationship between representation and spatial ability than between problem‐solving (representation and solution) and spatial ability.ConclusionsProblem‐solving can be considered to consist of two cognitively distinct phases: problem representation and problem solution. It was found that spatial ability is significantly related to problem representation but not to problem solution. Hence, this study shows that spatial ability plays a key role in engineering education that is not limited to visualization of imagery but extends to thinking during problem‐solving, a nonroutine activity that requires mental representation.
Frontline Science: AMPK regulates metabolic reprogramming necessary for interferon production in human plasmacytoid dendritic cells
Authors: Hurley Harry J , Dewald Hannah , Rothkopf Zachary S , Singh Sukhwinder , Jenkins Frank , Deb Pratik , De Saurav , Barnes Betsy J , Fitzgerald-Bocarsly Patricia 
Published: July 2020

Abstract
Plasmacytoid dendritic cells (pDCs) play a crucial role in innate viral immunity as the most potent producers of type I interferons (IFN) in the human body. However, the metabolic regulation of IFN production in such vast quantity remains poorly understood. In this study, AMP-activated protein kinase (AMPK) is strongly implicated as a driver of metabolic reprogramming that the authors and others have observed in pDCs after activation via TLR7/9. Oxygen consumption and mitochondrial membrane potential (MMP) were elevated following stimulation of pDCs with influenza or herpes simplex virus. Blocking these changes using mitochondrial inhibitors abrogated IFN-α production. While it appears that multiple carbon sources can be used by pDCs, blocking pyruvate metabolism had the strongest effect on IFN-α production. Furthermore, we saw no evidence of aerobic glycolysis (AG) during pDC activation and blocking lactate dehydrogenase activity did not inhibit IFN-α. TLR7/9 ligation induces a posttranslational modification in Raptor that is catalyzed by AMPK, and blocking TLR7/9 before virus introduction prevents this change. Finally, it is demonstrated that Dorsomorphin, an AMPK inhibitor, inhibited both IFN-α production and MMP in a dose-dependent manner. Taken together, these data reveal a potential cellular mechanism for the metabolic reprogramming in TLR 7/9-activated pDCs that supports activation and IFN-α production.
First molecular characterization of the hepatitis E virus in humans in Cameroon: Confirmation of the HEV outbreak in Touboro, North‐Cameroon
Authors: Modiyinji Abdou Fatawou , Rivero‐Juarez Antonio , Lopez‐Lopez Pedro , Atsama Marie Amougou , Monamele Chavely Gwladys , Nola Moise , Rivero Antonio , Njouom Richard 
Published: July 2020

AbstractHepatitis E virus (HEV) is a major causative agent of acute viral hepatitis in many regions of the world including Africa. In Cameroon, there is no published molecular study on HEV in humans. However, based on serological assays, the first outbreak of HEV was detected in North‐Cameroon. The objective of this study was to determine the molecular characterization of HEV that circulated during this period. A retrospective study design was used to select serum samples among those collected during the outbreak period. immunoglobulin M positive samples available in sufficient volumes to amplify HEV RNA were selected. RNA was extracted and then amplified by a real‐time reverse transcription polymerase chain reaction (real time RT‐PCR) assay, followed by a nested reverse transcription polymerase chain reaction (nested RT‐PCR) assay for sequencing and phylogenetic analysis. Overall, 24 samples were selected and HEV RNA was amplified by real‐time RT‐PCR in 20 samples. Amongst these, 12 samples were positive for HEV RNA by nested RT‐PCR and yielded good sequencing products. Phylogenetic analysis showed that 10 samples clustered with HEV genotype 1 (subtype 1e) and two samples clustered with HEV genotype 3 (subtype 3f). This study fills the gap of knowledge on the molecular epidemiology of HEV in Cameroon and confirms the first report of the hepatitis E outbreak in North‐Cameroon.
Utility of stabilized nitrogen fertilizers to reduce nitrate leaching under optimal management practices
Authors: Mateo-Marín Noemí , Quílez Dolores , Isla Ramón 
Published: July 2020

AbstractBackground: The inadequate application of nitrogen (N) to crops has increased the reactive N in the atmosphere and in the surface and ground waters. Stabilized N‐fertilizers with nitrification (NI) and urease (UI) inhibitors have been proposed to reduce these environmental problems without affecting or even increasing crop productivity.Aim: The objective of this study was to evaluate, in a maize–maize–wheat rotation, if the use of the NI 3,4‐dimethylpyrazole phosphate (DMPP) and the UIs N‐(n‐butyl) thiophosphoric triamide (NBPT) and monocarbamide dihydrogen sulfate (MCDHS) reduces N leaching without compromising yield under optimal management of N and water.Methods: The experiment was conducted in 24 drainage lysimeters with two soil types with contrasting water holding capacity under Mediterranean irrigated conditions. The fertilizer treatments were urea, urea with DMPP, urea with NBPT, and urea with MCDHS. For the maize crop, conventional fertilizer application was split into 6‐ and 13‐leaf stages, whereas stabilized fertilizers were applied as a single application at the 6‐leaf stage. All fertilizer treatments were applied at late tillering in the wheat crop.Results: The soil mineral N was measured at the beginning and the end of each crop season, but no differences were found among fertilizer treatments. Differences in the volume of water drained or the cumulative mass of nitrate depending on the fertilizer were not significant (three‐year treatment average of 200 L m−2 and 22 kg N ha−1 in the Deep soil, and 334 L m−2 and 40 kg N ha−1 in the Shallow type, respectively). No consistent significant differences were found in agronomic parameters (chlorophyll measurements, yield, and total N uptake) between the fertilizer treatments.Conclusion: Based on the results, the use of stabilized N‐fertilizer could be recommended to reduce the number of N applications in maize without compromising grain yield but with no advantages to reduce nitrate‐leaching losses if N rates are managed properly under efficient irrigation management practices.
Enzyme Scaffolds with Hierarchically Defined Properties via 3D Jet Writing
Authors: Steier Anke , Schmieg Barbara , Irtel von Brenndorff Yannic , Meier Manuel , Nirschl Hermann , Franzreb Matthias , Lahann Joerg 
Published: July 2020

AbstractThe immobilization of enzymes into polymer hydrogels is a versatile approach to improve their stability and utility in biotechnological and biomedical applications. However, these systems typically show limited enzyme activity, due to unfavorable pore dimensions and low enzyme accessibility. Here, 3D jet writing of water‐based bioinks, which contain preloaded enzymes, is used to prepare hydrogel scaffolds with well‐defined, tessellated micropores. After 3D jet writing, the scaffolds are chemically modified via photopolymerization to ensure mechanical stability. Enzyme loading and activity in the hydrogel scaffolds is fully retained over 3 d. Important structural parameters of the scaffolds such as pore size, pore geometry, and wall diameter are controlled with micrometer resolution to avoid mass‐transport limitations. It is demonstrated that scaffold pore sizes between 120 µm and 1 mm can be created by 3D jet writing approaching the length scales of free diffusion in the hydrogels substrates and resulting in high levels of enzyme activity (21.2% activity relative to free enzyme). With further work, a broad range of applications for enzyme‐laden hydrogel scaffolds including diagnostics and enzymatic cascade reactions is anticipated.
Durable, Sensitive, and Wide‐Range Wearable Pressure Sensors Based on Wavy‐Structured Flexible Conductive Composite Film
Authors: Shen Yepeng , Wang Yanbin , Luo Zhonglin , Wang Biaobing 
Published: July 2020

AbstractFlexible pressure sensors have potential applications in human motion monitoring and electronic skins. To satisfy the practical applications, pressure sensors with a high sensitivity, a low detection limit, a broad response range, and an excellent stability are highly needed. Here, a piezoresistive pressure sensor based on wavy‐structured single‐walled carbon nanotube/graphite flake/thermoplastic polyurethane (SWCNT/GF/TPU) composite film is fabricated by a prestretching process. Due to the random wavy structure, high conductivity, and good flexibility, the prepared sensor displays a low detection limit of 2 Pa, a wide sensing range of 0–60 kPa, and a high sensitivity of 5.49 kPa−1 for 0–50 Pa. Furthermore, the sensor shows a remarkable repeatability of over 1.1 × 104, 9.0 × 103, and 2.0 × 103 pressure loading/unloading cycles at 50 Pa, 500 Pa, and 30 kPa, respectively, and a fast responsibility of 100–150 ms of loading response time and 400–600 ms of relaxation time. Therefore, the pressure sensor is successfully adopted to monitor both the large‐scale human activities (e.g., walk and jump) and the small‐scale signals (e.g., wrist pulse). Furthermore, a sensor array is assembled to map the weight and shape of an object, indicating its various potential applications including human–machine interactions, human health monitoring, and other wearable electronics.
g‐natural symmetries on tangent bundles
Authors: Abbassi Mohamed Tahar Kadaoui , Amri Noura , Calvaruso Giovanni 
Published: July 2020

AbstractThe study of symmetries is a well known research topic in differential geometry with relevant physical interpretations. Given a Riemannian manifold , we consider pseudo‐Riemannian g‐natural metrics G on its tangent bundle and characterize conformal, homothetic and Killing vector fields of obtained from natural lifts of vector fields of M.
Multifield and inverse‐contrast switching of magnetocaloric high contrast ratio MRI labels
Authors: Barbic Mladen , Dodd Stephen J. , ElBidweihy Hatem , Dilley Neil R. , Marcheschi Barbara , Huston Alan L. , Morris H. Douglas , Koretsky Alan P. 
Published: July 2020

PurposeDemonstrating multifield and inverse contrast switching of magnetocaloric high contrast ratio MRI labels that either have increasing or decreasing moment versus temperature slopes depending on the material at physiological temperatures and different MRI magnetic field strengths.MethodsTwo iron‐rhodium samples of different purity (99% and 99.9%) and a lanthanum‐iron‐silicon sample were obtained from commercial vendors. Temperature and magnetic field‐dependent magnetic moment measurements of the samples were performed on a vibrating sample magnetometer. Temperature‐dependent MRI of different iron‐rhodium and lanthanum‐iron‐silicon samples were performed on 3 different MRI scanners at 1 Tesla (T), 4.7T, and 7T.ResultsSharp, first‐order magnetic phase transition of each iron‐rhodium sample at a physiologically relevant temperature (~37°C) but at different MRI magnetic fields (1T, 4.7T, and 7T, depending on the sample) showed clear image contrast changes in temperature‐dependent MRI. Iron‐rhodium and lanthanum‐iron‐silicon samples with sharp, first‐order magnetic phase transitions at the same MRI field of 1T and physiological temperature of 37°C, but with positive and negative slope of magnetization versus temperature, respectively, showed clear inverse contrast image changes. Temperature‐dependent MRI on individual microparticle samples of lanthanum‐iron‐silicon also showed sharp image contrast changes.ConclusionMagnetocaloric materials of different purity and composition were demonstrated to act as diverse high contrast ratio switchable MRI contrast agents. Thus, we show that a range of magnetocaloric materials can be optimized for unique image contrast response under MRI‐appropriate conditions at physiological temperatures and be controllably switched in situ.
Sleep, self‐management, neurocognitive function, and glycemia in emerging adults with Type 1 diabetes mellitus: A research protocol
Authors: Griggs Stephanie , Redeker Nancy S. , Crawford Sybil L. , Grey Margaret 
Published: July 2020

AbstractType 1 Diabetes (T1D) affects 1.6 million Americans, and only 14% of emerging adults ages 18–25 years achieve targets for glycemic control (A1C < 7.0%). Sleep deficiency, including habitual short sleep duration (<6.5 hr total sleep time and high within‐person variability in total sleep time), is associated with poorer glycemic control. Emerging adults with T1D have a more pronounced sleep extension on weekends compared with matched controls, consistent with sleep deficiency; however, associations among sleep variability and glycemic control have not been explored in this population. Sleep deficiency may affect the complex higher‐order neurocognitive functioning needed for successful diabetes self‐management (DSM). We report the protocol for an ongoing study designed to characterize sleep and the associations among sleep deficiency, neurocognitive function, DSM, diabetes quality of life, and glycemia among a sample of 40 emerging adults with T1D. We monitor sleep via wrist‐worn actigraphy and glucose via continuous glucose monitoring concurrently over 14 days. We are collecting data on self‐report and objective sleep, a 10‐min psychomotor vigilance test on a PVT‐192 device, a 3‐min Trail Making Test on paper, and questionnaires, including twice‐daily Pittsburgh sleep diaries using Research Electronic Data Capture (REDCap)TM. Results from this study will be used to support the development and testing of the efficacy of a tailored sleep self‐management intervention that may improve total sleep time, sleep variability, neurocognitive function, DSM, glycemic control, and glucose variability among emerging adults with T1D.
Properties of gradient polyimide aerogels prepared through layer‐by‐layer assembly
Authors: Yuan Shuaiwei , Yu Zhi , Wu Peng , Zhou Shengtai , Zou Huawei , Liu Pengbo 
Published: July 2020

AbstractA series of density gradient polyimide (PI) aerogels were prepared using layer‐by‐layer assembly and radial freezing method. Briefly, a layer of poly(amic acid) (PAA) ammonium salt aqueous solution was first radially frozen. Then, the second layer of PAA ammonium salt (PAS) aqueous solution of different concentration was added on the top of the first PAS layer and radially frozen. A multilayer gradient PAS solid sample could therefore be fabricated by repeating this similar procedure. The density gradient PI aerogels were obtained after freezing drying and final thermal imidization treatment. Each layer of gradient PI aerogels had anisotropic pore structure, which consisted of tube‐like pores along the radial direction and toward the center axis of the cylindrical samples. The compressive strength of five‐layer gradient PI aerogel was higher than that of three‐layer gradient and single‐layer PI aerogels with the same density. The gradient PI aerogels exhibited anisotropic heat transfer behavior in the direction of density gradient, and heat transfer from the higher density side to the lower density side was faster.