bluuebunny/crossref_metadata_2025_split huggingface dataset:
Effects of RORγt overexpression on the murine central nervous system
Authors: Sasaki Tetsuya , Nagata Rei , Takahashi Satoru , Takei Yosuke 
Published: February 2021

AbstractObjectiveT helper 17 (Th17) cells are a subset of CD4+ T cells that produce interleukin (IL)‐17A. Recent studies showed that an increase in circulating IL‐17A causes cognitive dysfunction, although it is unknown how increased systemic IL‐17A affects brain function. Using transgenic mice overexpressing RORγt, a transcription factor essential for differentiation of Th17 cells (RORγt Tg mice), we examined changes in the brain caused by chronically increased IL‐17A resulting from excessive activation of Th17 cells.ResultsRORγt Tg mice exhibited elevated Rorc and IL‐17A mRNA expression in the colon, as well as a chronic increase in circulating IL‐17A. We found that the immunoreactivity of Iba1 and density of microglia were lower in the dentate gyrus of RORγt Tg mice compared with wild‐type mice. However, GFAP+ astrocytes were unchanged in the hippocampi of RORγt Tg mice. Levels of synaptic proteins were not significantly different between RORγt Tg and wild‐type mouse brains. In addition, novel object location test results indicated no difference in preference between these mice.ConclusionOur findings indicate that a continuous increase of IL‐17A in response to RORγt overexpression resulted in decreased microglia activity in the dentate gyrus, but had only a subtle effect on murine hippocampal functions.
Geophysical investigations for the identification of active seismic faults below alluvium for seismic hazard assessment
Authors: Cercato Michele , De Donno Giorgio , Desideri Francesco Saverio , Di Giambattista Luca 
Published: February 2021

ABSTRACTThe existence of active faults hidden below Quaternary alluvium is a common geological scenario for intermontane basins, such as the areas struck by the recent earthquakes in Central Italy, and is of great importance for seismic hazard evaluation. Finding hidden faults is a challenging task from the geophysicist's point of view since the goal is twofold: to identify the seismic bedrock at a certain depth; and to detect lateral variations or dislocations that may indicate the presence of a fault. We propose a mixed approach encompassing at first single‐station seismic noise measurements, to detect sudden lateral variations in the bedrock surface in a fast and cost‐effective way, which might serve as a proxy for the potential identification of fault zones. Then, more accurate electrical resistivity tomography investigations are carried out only at selected sites as indicated by the preliminary noise analysis, as electrical methods cannot effectively be employed at a large scale for time and economic limitations. Surface‐wave dispersion analysis is jointly interpreted together with ambient noise data to improve the seismic characterization of the alluvium, giving further insight on the assessment of the depth to bedrock. The proposed approach can be an effective way to manage and investigate a large portion of the territory within a sensible budget, as commonly needed in seismic hazard assessment and microzonation studies. We present a real‐world application to the San Vittorino Plain (Central Italy) close to the epicentre of the 24 August 2016 Amatrice earthquake, where the geological faulted bedrock is covered by alluvial sediments of the Velino River up to a maximum estimated thickness of 150–200 m. Although engineered for the post‐earthquake reconstruction emergency, the approach employed in our study can be adopted in other areas of similar geology, to ease the application of seismic microzonation in time of seismic silence as a tool for long‐term land planning and management.
The Effect of Concomitant Proton Pump Inhibitor and Cabozantinib on the Outcomes of Patients with Metastatic Renal Cell Carcinoma
Authors: Rassy Elie , Cerbone Luigi , Auclin Edouard , Benchimoll-Zouari Axelle , Flippot Ronan , Alves Costa Silva Carolina , Colomba Emeline , Geraud Arthur , Guida Annalisa , Mir Olivier , Combarel David , Paci Angelo , Escudier Bernard , Albiges Laurence 
Published: February 2021

Abstract

Introduction
Cabozantinib is an oral tyrosine kinase inhibitor that is approved for the treatment of metastatic renal cell carcinoma (mRCC). Cabozantinib is a weak base that exhibits a pH-dependent solubility profile in vitro which raises concerns about its bioavailability in patients treated with proton pump inhibitors (PPIs). The purpose of this study was to investigate whether PPI use has an impact on the efficacy, safety, and residual concentration (Ctrough) of cabozantinib in patients with mRCC.

Materials and Methods
This is a retrospective review of a prospectively collected electronic database of patients with mRCC who received cabozantinib at Gustave Roussy between February 2014 and December 2018. The Kaplan-Meier method was used for survival analysis and the Cox proportional-hazard model for uni- and multivariate analysis. In parallel, we conducted a pharmacokinetic study of cabozantinib in a distinct cohort of 50 mRCC patients, in which cabozantinib Ctrough was assayed using a validated tandem mass spectrometry–liquid chromatography method.

Results
We identified 99 patients treated with cabozantinib, including 43 patients being PPI users. With a median follow-up of 30.3 months, PPI users showed similar progression-free survival and overall survival outcomes compared with PPI nonusers. Similarly, the incidence of adverse events was not significantly different between the PPI users and nonusers, although PPI users required dose reductions more often. In the independent pharmacokinetic cohort, of whom 21 received PPI concomitantly, Ctrough was similar between the two groups.

Conclusion
In line with the pharmacologic data, the concomitant use of PPI does not significantly impact the efficacy or safety of cabozantinib in patients with mRCC.

Implications for Practice
Drug interactions, especially between targeted therapies and proton pump inhibitors (PPI), were shown to potentially impact the outcomes of cancer patients. Cabozantinib, a current therapeutic standard in metastatic renal cell carcinoma (mRCC), exhibits a pH-dependent solubility profile, which raises concerns about its bioavailability in patients treated with proton pump inhibitors (PPI). At the present time, there is no evidence regarding the effect of PPIs on cabozantinib's efficacy and safety in patients with mRCC. This study found that the concomitant use of PPI during cabozantinib treatment in mRCC patients does not appear to impact the residual concentration, efficacy, and safety of cabozantinib in a real-life context.
A Novel Malignant Peritoneal Mesothelioma with STRN Exon 2 and ALK Exon 20: A Case Report and Literature Review
Authors: Miyagawa Chiho , Takaya Hisamitsu , Sakai Kazuko , Nishio Kazuto , Konishi Maho , Minamiguchi Sachiko , Shimada Toshihide , Matsumura Noriomi 
Published: February 2021

Abstract

Recently, several malignant peritoneal mesotheliomas (MPMs), occurring in young women without asbestos exposure and with fusion genes such as anaplastic lymphoma kinase (ALK) and Ewing sarcoma breakpoint region 1, have been reported. In the present case, we encountered MPM with STRN-ALK fusion in a 17-year-old female adolescent. The case did not respond to chemotherapy and is currently in a clinical trial of alectinib. This is the fourth reported case of MPM with STRN-ALK fusion. Of the 45 cancer cases with STRN-ALK fusion in which the fusion partners were examined, all cases except for the current case showed fusion of exon 3 of STRN and exon 20 of ALK. This is the first case with fusion of exon 2 of STRN and exon 20 of ALK. Further advances in cancer genomic medicine may help clarify the clinical significance of this new fusion.

Key Points
Malignant peritoneal mesotheliomas (MPMs) can occur in young women without asbestos exposure and show fusion genes that activate anaplastic lymphoma kinase (ALK) by gene rearrangement. ALK rearrangement and the fusion partner can be detected by companion diagnostics and by next generation sequencing. Patients with MPMs with ALK rearrangement may benefit from target therapy.
FINANCING THE WAR ON DRUGS: THE IMPACT OF LAW ENFORCEMENT GRANTS ON RACIAL DISPARITIES IN DRUG ARRESTS
Authors: Cox Robynn , Cunningham Jamein P. 
Published: February 2021

AbstractThis study estimates the impact of the discretionary Edward Byrne Memorial State and Local Law Enforcement Assistance Program (EBMGP) on drug arrests and crime. The 1986 and 1988 Anti‐Drug Abuse Act allocated federal funds to state and local municipalities to combat illicit drug use and violent crime associated with drug sales and trafficking. The results show that the implementation of the EBMGP resulted in an increase in police hiring, an increase in drug sales arrest rates for Blacks and Whites, and a decrease in total crime. Nonetheless, Black‐White racial disparity in the drug sales arrest rate still significantly increases by approximately 1 for every 1,000 Black residents. Our findings highlight the role of federal crime control policies in state and local policing. Although, the EBMGP was a color‐blind policy initiative, it was not race neutral in its implementation.
Experimental and numerical investigation of T‐joints with multiwalled carbon nanotubes
Authors: Li Qian , Zhu Ming , Tao Guo Quan , Xie Cong 
Published: February 2021

AbstractCombined experimental and numerical methods were used to study the mechanical properties of multiwalled carbon nanotubes (MWCNTs) enhanced composite T‐joints in this article. Herein, an enhanced interface model was created based on the interface mechanical properties with MWCNTs obtained by a flatwise tension test and a single‐lap shear test. Then, the finite element model of composite T‐joints with MWCNTs was developed with a cohesive zone model to study the damage initiation, evolution, and final failure process of T‐joints. Meanwhile, a quasi‐static tensile test of the T‐joints was carried out to compare with the numerical analysis results. The study results showed that the out‐of‐plane tensile strength and the in‐plane shear strength of MWCNTs enhanced composite increased by up to 26.3%(@3 g/m2) and 23.4%(@2 g/m2), respectively. The properties of the filler, which was the weakest part of the T‐joints, can be enhanced by adding MWCNTs. The overall bearing capacity of the T‐joints was 18.8%(@2 g/m2 MWCNTs) increase under tensile loading. Predictions given by the FEM of composite T‐joints were in good agreement with the experimental results. This article provides a method for analyzing and predicting the complex composite structure enhanced with MWCNTs, which can be used for functional structure design.
When learners lead themselves: A psychometric investigation of the Revised Self‐Leadership Questionnaire in Thais
Authors: Boonyarit Itsara 
Published: February 2021

AbstractSelf‐leadership is an ability to influence oneself, which is considered as an instrumental part of personal effectiveness. In the current study, the Revised Self‐Leadership Questionnaire was translated into Thai, called the RSLQ‐Thai Version, and its psychometric properties of construct validity were examined using structural equation modeling. Packages of questionnaires, including the RSLQ‐Thai Version and its related variables, were administered to 350 undergraduate students in a university located in North Thailand. Data were analysed using structural equation modeling. Results provided support for the evidence of the construct validity of the RSLQ‐Thai Version. Evidence for convergent validity, a second‐order factor model of self‐leadership, with respect to the two alternative models, reported better fit indices. This means that the scale is assessing self‐leadership, which is consistent with its own theoretical construct. Moreover, dimensions of self‐leadership were distinct from extraversion and conscientiousness, revealing evidence of discriminant validity. Evidence of nomological validity supported the theoretical network of the self‐leadership construct. Self‐leadership had a significant positive direct effect on academic self‐efficacy and had positive indirect effects on satisfaction with life, flourishing, and academic performance through academic self‐efficacy as the mediator. Implications for future research are discussed.
Strategies to attenuate the competence regulon in Streptococcus pneumoniae
Authors: Lella Muralikrishna , Tal‐Gan Yftah 
Published: February 2021

AbstractStreptococcus pneumoniae is an opportunistic respiratory human pathogen that poses a continuing threat to human health. Natural competence for genetic transformation in S. pneumoniae plays an important role in aiding pathogenicity and it is the best‐characterized feature to acquire antimicrobial resistance genes by a frequent process of recombination. In S. pneumoniae, competence, along with virulence factor production, is controlled by a cell‐density communication mechanism termed the competence regulon. In this review, we present the recent advances in the development of alternative methods to attenuate the pathogenicity of S. pneumoniae by targeting the various stages of the non‐essential competence regulon communication system. We mainly focus on new developments related to competitively intercepting the competence regulon signaling through the introduction of promising dominant‐negative Competence Stimulating Peptide (CSP) scaffolds. We also discuss recent reports on antibiotics that can block CSP export by disturbing the proton motive force across the membrane and various ways to control the pneumococcal pathogenicity by activating the counter signaling circuit and targeting the pneumococcal proteome.
Tailoring the rheology and electrical properties of polyamide 66 nanocomposites with hybrid filler approach: graphene and carbon nanotubes
Authors: Palacios Jordana K , Ben Fekih Achraf , Yus Argon Cristina , Irusta Silvia , Jestin Simon , Dagréou Sylvie 
Published: February 2021

AbstractThe aim was to improve the processability and reduce the melt viscosity of well‐known nanocomposites based on polyamide 66 (PA66) and carbon nanotubes (CNT), while keeping the good electrical conductivity gained after the addition of CNT. Thus, a nanocomposite based on PA66 as the thermoplastic matrix and 3% of CNT was selected. At this composition, a percolated network is created and the material is electrically conductive. The approach followed was the addition of graphene nanoplatelets (GNP) of two different lateral sizes to obtain a PA66 nanocomposite with hybrid filler: CNT/GNP. In addition, a third nanocomposite of PA66 with GNP only was prepared for comparison purposes. The rheological characterization determined that adding 1% of GNP of 2 μm particle size decreased the viscosity of the system by 87%. However, the electrical conductivity was diminished to some extent, from 10−5to 10−9 S cm−1approximately. The Cross rheology model described successfully the experimental rheological data. The CNT/GNP nanocomposite exhibited faster relaxations, almost four orders of magnitude, in comparison with the CNT nanocomposite but slower than the GNP nanocomposite. The nanoparticles improved the crystallization ability of PA66 acting as nucleating agents and increasing the PA66 crystallization temperature by almost 10 °C. Self‐nucleation experiments demonstrated a supernucleation feature of the hybrid filler. The nucleation efficiency was about 500%. © 2021 Society of Chemical Industry
The sputter deposition of broadband transparent and highly conductive cerium and hydrogen co‐doped indium oxide and its transfer to silicon heterojunction solar cells
Authors: Tutsch Leonard , Sai Hitoshi , Matsui Takuya , Bivour Martin , Hermle Martin , Koida Takashi 
Published: February 2021

AbstractIndium oxide doped with tin (ITO) is the most commonly used material for lateral transport window layers in silicon heterojunction (SHJ) solar cells, as it currently offers the best combination of physical properties, industrial deposition capability, and module reliability. However, typically applied ITO layers by far do not exploit the full electro‐optical potential of the indium oxide material class, resulting in optical and electrical losses limiting the solar cell efficiency. In this work, cerium and hydrogen co‐doped indium oxide thin films are developed for their application as high‐performance transparent conductive oxide layers in SHJ devices. Amorphous In2O3:Ce,H layers are fabricated via radio frequency magnetron sputtering, before being crystallized during post‐deposition thermal treatments compatible with the SHJ temperature stability. The resulting excellent electro‐optical film properties are on par with values so far solely reported for reactive plasma deposited films. It is shown that the surface morphology of the substrate (planar or textured) has a strong impact on the film properties, and further, the critical role of the atmosphere present during post‐deposition annealing is elucidated. Finally, the large potential of an optimally processed In2O3:Ce,H window layer in SHJ cells is demonstrated, quantified by a gain in short circuit current density of 0.6 mA/cm2 without impairing the resistive losses in comparison to the usage of a baseline ITO layer.
Effect of natural extract from waste corn meal on stabilization of natural rubber
Authors: Promhuad Khwanchat , Prasopdee Thridsawan , Smitthipong Wirasak 
Published: February 2021

AbstractNatural rubber (NR) consists of rubber and non‐rubber components. Under prolonged storage, non‐rubber components of NR promote network or gel formation and increase Mooney viscosity, a phenomenon otherwise known as the storage hardening phenomenon. Generally, NR properties can be stabilized by commercial synthetic stabilizers such as hydroxylamine sulfate, hydrazine stearate, and so forth. The objective of this study is to prepare constant viscosity (CV) NR with natural extract (NE) from waste corn meal. The effect of NE on storage hardening of NR was investigated. Several types of samples were prepared: NR without stabilizer, NR with 0.1, 0.2, 0.5, 1.0, and 2.0 phr (parts per hundred rubber) of NE. Samples were characterized immediately and after 12 weeks of storage time at room temperature. Physical and mechanical properties of all NR samples changed with time, but less with 2.0 phr NE because it inhibits network formation within NR. These results suggest NE is a natural stabilizer for preparing environmentally friendly CV natural rubber.
Phenyl(triazolyl)carbene revisited: Unique role of triazolyl group on carbene chemistry
Authors: Hirai Katsuyuki , Yamaguchi Masao , Okazaki Takao , Kitagawa Toshikazu , Tomioka Hideo 
Published: February 2021

AbstractThe chemistry of (1,4‐diphenyl‐1H‐1,2,3‐triazol‐5‐yl)(phenyl)carbenes (1T), originally reported by Smith et al., was reinvestigated by using modern spectroscopic methods as well as density functional theory (DFT) calculations, and the results were compared with that observed for analogous diphenylcarbene (1H) to clarify the role of triazole group in diarylcarbene chemistry. Product analysis indicated that 1T gave two intramolecular cyclization products (2 and 3) formed as a result of a formal attack of carbene on the phenyl rings at 1‐ and 4‐positions of the triazole ring. The results were closely similar to that observed for 1H. The behaviors of triplet carbene 31T were directly monitored not only by electron spin resonance (ESR) and UV‐Vis spectroscopic methods in rigid matrix at low temperature but also by laser flash photolysis in solution at room temperature and compared with those observed for 31H. Whereas the lifetime of 31T was some 2 orders of magnitude longer than that of 31H, the reactivity of 31T toward typical triplet trapping reagents was greater than that of 31H. In order to elucidate these rather conflicting observations, geometries and relative energies of carbenes 1T and 1H as well as species involved in the reactions leading to the final products were calculated by the DFT method. The results are interpreted as indicating that 31H decays by participating in the reaction of upper‐lying 11H much more easily than 31T. The difference in the reactivity toward external trapping reagents is explicable by taking into account the difference in steric crowdedness around carbene center between the two.
Unveiling the binding mode of perfluorooctanoic acid to human serum albumin
Authors: Maso Lorenzo , Trande Matteo , Liberi Stefano , Moro Giulia , Daems Elise , Linciano Sara , Sobott Frank , Covaceuszach Sonia , Cassetta Alberto , Fasolato Silvano , Moretto Ligia M. , De Wael Karolien , Cendron Laura , Angelini Alessandro 
Published: February 2021

AbstractPerfluorooctanoic acid (PFOA) is a toxic compound that is absorbed and distributed throughout the body by noncovalent binding to serum proteins such as human serum albumin (hSA). Though the interaction between PFOA and hSA has been already assessed using various analytical techniques, a high resolution and detailed analysis of the binding mode is still lacking. We report here the crystal structure of hSA in complex with PFOA and a medium‐chain saturated fatty acid (FA). A total of eight distinct binding sites, four occupied by PFOAs and four by FAs, have been identified. In solution binding studies confirmed the 4:1 PFOA‐hSA stoichiometry and revealed the presence of one high and three low affinity binding sites. Competition experiments with known hSA‐binding drugs allowed locating the high affinity binding site in sub‐domain IIIA. The elucidation of the molecular basis of the interaction between PFOA and hSA might provide not only a better assessment of the absorption and elimination mechanisms of these compounds in vivo but also have implications for the development of novel molecular receptors for diagnostic and biotechnological applications.
Effect of mitoquinone on liver metabolism and steatosis in obese and diabetic rats
Authors: Fink Brian D. , Yu Liping , Coppey Lawrence , Obrosov Alexander , Shevalye Hanna , Kerns Robert J. , Yorek Mark A. , Sivitz William I. 
Published: February 2021

AbstractPrevious work by ourselves and others showed that mitoquinone (mitoQ) reduced oxidative damage and prevented hepatic fat accumulation in mice made obese with high‐fat (HF) feeding. Here we extended these studies to examine the effect of mitoQ on parameters affecting liver function in rats treated with HF to induce obesity and in rats treated with HF plus streptozotocin (STZ) to model a severe form of type 2 diabetes. In prior reported work, we found that mitoQ significantly improved glycemia based on glucose tolerance data in HF rats but not in the diabetic rats. Here we found only non‐significant reductions in insulin and glucose measured in the fed state at sacrifice in the HF mice treated with mitoQ. Metabolomic data showed that mitoQ altered several hepatic metabolic pathways in HF‐fed obese rats toward those observed in control normal chow‐fed non‐obese rats. However, mitoQ had little effect on pathways observed in the diabetic rats, wherein diabetes itself induced marked pathway aberrations. MitoQ did not alter respiration or membrane potential in isolated liver mitochondria. MitoQ reduced liver fat and liver hydroperoxide levels but did not improve liver function as marked by circulating levels of aspartate and alanine aminotransferase (ALT). In summary, our results for HF‐fed rats are consistent with past findings in HF‐fed mice indicating decreased liver lipid hydroperoxides (LPO) and improved glycemia. However, in contrast to the HF obese mice, mitoQ did not improve glycemia or reset perturbed metabolic pathways in the diabetic rats.