bluuebunny/crossref_metadata_2025_split huggingface dataset:
Vascular age is associated with the risk of dialysis or death in chronic kidney disease
Authors: Lin Miao , Chan Gary CW , Chan Kam W , Lai Kar N , Tang Sydney CW 
Published: June 2019

ABSTRACTAimIncreased arterial stiffness is associated with progressive renal deterioration and poor clinical outcomes in patients with chronic kidney disease (CKD). Assessment of vascular age as derived from arterial stiffness parameters might be an important clinical marker of cardiovascular risks. The aim of the present study is to evaluate whether the difference (△age) between vascular age and chronological age can predict the risk of reaching dialysis or death in patients with known CKD.MethodsThis longitudinal study enrolled 94 male Chinese CKD patients, aged 40–62 years. Vascular age was calculated by brachial‐ankle pulse wave velocity, and measured by an ankle‐brachial index‐form device. The study endpoints were the commencement of renal replacement therapy or death.ResultsAfter a stepwise multivariate analysis, △age was associated independently with increased urine protein‐to‐creatinine ratio (β = 0.32; P = 0.001) and decreased baseline estimated glomerular filtration rate (β = −0.24; P = 0.008). During a median follow‐up period of 62 (interquartile range = 55–66) months, the 4‐year cumulative incidence of reaching the study endpoint in patients with △age = 0 and △age > 0 year was 4.9% and 25%, respectively (log–rank test, P = 0.009). Multivariate forward Cox regression analysis identified that higher △age (hazard ratio (HR) = 1.05; P = 0.027), lower baseline estimated glomerular filtration rate (HR = 0.93; P < 0.001), and history of cardiovascular disease (HR = 5.90; P = 0.031) were independently associated with progression to commencement of dialysis or death.ConclusionThus, the assessment of the difference between vascular age and chronological age may provide an alternative method to identify CKD patients at a high risk of progression to dialysis or death.
Young sex chromosomes in plants and animals
Authors: Charlesworth Deborah 
Published: June 2019

SummaryA major reason for studying plant sex chromosomes is that they may often be ‘young’ systems. There is considerable evidence for the independent evolution of separate sexes within plant families or genera, in some cases showing that the maximum possible time during which their sex‐determining genes have existed must be much shorter than those of several animal taxa. Consequently, their sex‐linked regions could either have evolved soon after genetic sex determination arose or considerably later. Plants, therefore, include species with both young and old systems. I review several questions about the evolution of sex‐determining systems and sex chromosomes that require studies of young systems, including: the kinds of mutations involved in the transition to unisexual reproduction from hermaphroditism or monoecy (a form of functional hermaphroditism); the times when they arose; and the extent to which the properties of sex‐linked regions of genomes reflect responses to new selective situations created by the presence of a sex‐determining locus. I also evaluate which questions are best studied in plants, vs other suitable candidate organisms. Studies of young plant systems can help understand general evolutionary processes that are shared with the sex chromosomes of other organisms.
The Dimensions of Agricultural Diversification: A Spatial Analysis of Italian Municipalities
Authors: Mazzocchi Chiara , Orsi Luigi , Ferrazzi Giovanni , Corsi Stefano 
Published: June 2019

AbstractDiversification in agriculture could ensure the survival of farming by broadening the income base of farms and encouraging agricultural sustainability. The diversification of on‐farm activities may depend on socioeconomic and environmental characteristics. Although multifunctionality is a hotly debated topic, few papers have focused on the farm characteristics that influence diversification and none have focused on the influence of the spatial pattern. This paper examines the relationship between farm characteristics and the adoption of a specific type of diversification. An econometric model is presented that uses a spatial autoregressive lag model at the municipal scale. The results demonstrate that the activation of each diversification dimension is influenced by both internal and external factors, encompassing farmers’ characteristics, the farm structure, and territorial features, including regional and spatial patterns. Deepening is mainly influenced by the farmer’s age, education, and the presence of small and labor‐intensive farms. The key factors for broadening diversification are the presence of small farms and farms with mixed production (breeding and crop cultivation). Regrounding is most affected by the labor‐intensive farms in the area and the farms with mixed production.
A pilot study comparing bone marrow aspirates and venous blood for emergency point‐of‐care blood parameters in healthy dogs
Authors: Ackert Lindsey , Boysen Søren R. , Schiller Teresa 
Published: June 2019

AbstractObjectiveTo compare intravenous and intraosseous blood aspirates using point‐of‐care diagnostic equipment available in veterinary hospitals.DesignProspective study.SettingPrivate referral hospital.AnimalsDogs undergoing a tibial plateau leveling osteotomy or extracapsular anterior cruciate ligament stabilization procedure were enrolled.MethodsUnder general anesthesia, simultaneous 0.5 mL intravenous and intraosseous blood samples were collected from the jugular vein and proximal tibia, respectively. Samples were evaluated in duplicate within 10 minutes of collection and averaged for each of the following parameters: blood urea nitrogen (BUN), glucose, packed cell volume, total plasma protein (TPP), plasma lactate, sodium, potassium, chloride, urea, glucose, pH, anion gap, pO2, and pCO2. Normalcy was tested with Kolmogorov–Smirnov test. A Student's t‐test and Bland–Altman plot were used to compare intravenous and intraosseous samples.ResultsTwelve dogs were recruited into the study. There were statistically significant differences between intravenous and intraosseous samples for sodium (P = 0.0216), chloride (P = 0.0225), BUN (P = 0.014), and potassium (P < 0.0001), respectively. No significant differences were detected for the other parameters evaluated.DiscussionThe intraosseous space provides an easily accessible, noncollapsible alternative for assessing blood parameters. Omitting potassium, the statistically significant differences noted between sites was not felt to be clinically significant. Although statistically insignificant, the large difference in hematocrit values indicates that the samples should not be used interchangeably.ConclusionIntraosseous aspirates, excluding potassium and hematocrit, appear to be a reliable alternative for assessing most point‐of‐care analytes in healthy dogs, although a larger sample size should be investigated. The application of these data in shock patients is unknown.
Effect of a continuous epitendinous suture as adjunct to three‐loop pulley and locking‐loop patterns for flexor tendon repair in a canine model
Authors: Putterman Allison B. , Duffy Daniel J. , Kersh Mariana E. , Rahman Hafizur , Moore George E. 
Published: June 2019

AbstractObjectiveTo evaluate the effect of combining a continuous epitendinous suture with three‐loop pulley (3LP) and locking‐loop (LL) core patterns for flexor tendon repair.Study designEx vivo biomechanical study.Sample populationSeventy‐two cadaveric superficial digital flexor musculotendon (SDFT) units.MethodsTendons were divided into four groups (n = 18/group). After sharp transection, SDFT were repaired with 3LP, LL, 3LP + epitendinous (E), or LL + E suture patterns. After preloading, repaired constructs were tested to failure. Video data acquisition allowed evaluation of failure mode and quantitation of gap formation. Yield, peak, and failure force were measured from force‐displacement data. Significance was set at P < .05.ResultsMode of failure did not differ between repairs with or without an epitendinous suture (P = .255). Gap formation was best prevented with 3LP compared with LL when used alone (P = .001). Mean yield force for 3LP, LL, 3LP + E, and LL + E were 91.4 N ± 25.4, 61.3 N ± 18.4, 195.2 N ± 66.0, 165.3 N ± 46.8, respectively. Tenorrhaphies combined with an epitendinous suture achieved higher yield (P < .0001), peak (P < .0001), and failure forces (P < .0001), without gapping between tendon ends.ConclusionAddition of an epitendinous suture eliminated gapping between tendon ends until failure and increased resistance to loads tolerated at the repair site.Clinical significanceThe addition of an epitendinous suture may increase the strength of tendon repairs and resistance to gap formation over core suture use alone. The influence of epitendinous suture placement on tendinous healing and blood supply warrants in‐vivo testing.
Highly Concentrated Aqueous Electrolyte With a Large Stable Potential Window for Electrochemical Double-Layer Capacitors
Authors: Zhang Guoqing , Zhao Yongqing , Jin Binbin , Zhang Peng , Kong Shuying 
Published: June 2019

Abstract
An active carbon (AC)/AC electrochemical capacitor, taking advantage of a high-concentrated lithium trifluoromethane sulfonate (LiTFS) or lithium bis(trifluoromethane sulfonyl) imide (LiTFSI) aqueous electrolyte, was demonstrated with an extended operating voltage of 2.5 V, which is the largest value till now for aqueous carbon-based capacitors. The AC electrode is entirely capacitive in these two electrolytes and the stable potential window of the single AC electrode can reach −1.2 to 1.2 V versus the saturated calomel electrode (SCE). The performance of the AC-based capacitor is evaluated in two- and three-electrode cells using a combination of electrochemical impedance (EIS), cyclic voltammetry (CV), galvanostatic discharge-charge, and self-discharge (SD, i.e., leakage current) measurements. At 0.5-mA cm−2 charge-discharge rate, the AC/AC capacitor presents 5.5 wh kg−1 and 4.5 wh kg−1 energy density for 20 m LiTFS and LiTFSI electrolyte, respectively. The results suggest that a thorough utilization of such lithium salt aqueous electrolytes with widening electrochemical stable potential window will no doubt lead to further development of electrochemical capacitors toward superior performance.
AAC Olive marrowfat pea
Authors: Bing Deng-Jin , Beauchesne Don , McLaren Debra , Gan Yantai , Balasubramanian Parthiba , Naeem Hamid 
Published: June 2019

AAC Olive is a semi-leafless, green cotyledon, and high-yielding marrowfat pea (Pisum sativum L.) variety developed at the Lacombe Research and Development Centre, Agriculture and Agri-Food Canada. It has a maturity of 102 d, average thousand-seed weight of 344 g, and is resistant to powdery mildew (caused by Erysiphe pisi). AAC Olive was certificated on 16 Apr. 2019 by the Canadian Seed Growers Association under the authority of the Canada Seeds Act. The certificate number is 2165-2019.
First-principles study of the structural, electronic, magnetic, elastic and optical properties of CoFeZrSi1−xGex(x = 0.00, 0.25, 0.50, 0.75, 1.00)
Authors: Paudel Ramesh , Zhu Jingchuan 
Published: June 2019

The effect of germanium doping on the structural, magnetic, elastic and optical properties of the LiMgPdSn-type CoFeZrSi[Formula: see text]Ge[Formula: see text] alloys is predicted by utilizing ab initio density functional theory (DFT) with the generalized gradient approximation (GGA) and the electronic properties of the materials are investigated by using the generalized gradient approximation plus Hubbard coefficient (GGA + U). The estimated elevated lattice constant of CoFeZrGe compound agrees with existing theoretical data. The optimized lattice constants of CoFeZrSi[Formula: see text]Ge[Formula: see text](x = 0, 0.25, 0.50, 0.75) are 5.9022, 5.9631, 5.9752 and 5.9973 Å, respectively. These have been investigated for the very first time. The elastic symmetry (C[Formula: see text], C[Formula: see text], C[Formula: see text], C[Formula: see text], C[Formula: see text] and C[Formula: see text]), bulk modulus, shear modulus, Poisson’s ratio, anisotropy and Pugh ratio (B/G) are predicted and discussed. The calculation of band structure and density of states reveal that the materials considered have half-metallic behavior with 100% spin-polarization. The calculated magnetic moments of CoFeZrSi[Formula: see text]Ge[Formula: see text] are 0.99, 1.06, 1.02, 1.00 and 1.01 [Formula: see text], respectively, and agree with the SP rule, M[Formula: see text] = N[Formula: see text] − 24. The analysis of the elastic moduli indicates that the compounds are mechanically stable with a ductile nature. The CoFeZrSi[Formula: see text]Ge[Formula: see text] alloy is stiffer than the other compounds considered. Moreover, the dielectric functions, optical conductivity, reflectivity and absorption coefficient of CoFeZrSi[Formula: see text]Ge[Formula: see text] compounds are predicted by using complex dielectric functions.
Investigations on surface morphologies, microstructure and thermal properties of tungsten-based composites
Authors: Demir Ertuğrul , Mirzayev Matlab N. , Tugrul A. Beril , Gledenov Yury M. , Turchenko Vitali A. , Yılmaz Ozan , Büyük Bülent , Öveçoğlu M. Lütfi 
Published: June 2019

The purpose of this research is to determine the surface morphologies, microstructural and thermal properties of tungsten-based composites that consist of 93 wt.% tungsten (W), 6 wt.% vanadium carbide (VC) and 1 wt.% graphite (C) powders. W-6 wt.% VC-1 wt.% C powders were mechanically alloyed (MA’d) for 6 hrs using a [Formula: see text] with a rate rpm using tungsten carbide vial and balls and sintered at [Formula: see text] for under [Formula: see text], [Formula: see text] gas flow conditions. The phase composition and microstructural characterization of the tungsten composites were carried out using X-ray diffractometer (XRD), Scanning Electron Microscopy (SEM) and Raman Spectroscopy. SEM images showed the distribution of the tungsten (W), vanadium carbide (VC) and graphite (C) powders and porosity in the tungsten matrix. The Raman spectra exhibited two major peaks, which are recorded at 1331 (vs) [Formula: see text] and 1583 (vs) [Formula: see text] in the Raman spectra. These bands represented carbon phases such as disordered graphite (D) and graphite (G). Thermogravimetric analysis (TGA) measurements were performed to obtain the weight loss and thermal stability of samples in the temperature range [Formula: see text]–[Formula: see text] under argon gas atmosphere. The TG curve revealed a total loss of 3.3% of weight at this temperature range. It is considered that the cause of mass loss is due to the oxidation and gas desorption of materials.
INSIGHT INTO STRUCTURAL, OPTICAL AND ELECTRICAL PROPERTIES OF COBALT OXIDE Co3O4 THIN FILM
Authors: BOUREGUIG K. M. E. , TABET-DERRAZ H. , SEDDIK T. 
Published: June 2019

In the present paper, experimental investigations on structural, morphological, optical and electrical properties of Co3O4 thin film deposited by spray pyrolysis method are reported. Using the interplanar spacing of the XRD reflection and Scherrer formula, respectively, we observed that the obtained films identified crystallize in the cubic spinel structure with [Formula: see text] nm and [Formula: see text] nm. From the SEM picture, a dense grain in the morphology of Co3O4 is detected which has a uniform spherical shape. In addition, transmittance, absorbance, optical bandgap and extinction coefficient of the film versus incident photon energy were calculated. We found that Co3O4 film has a direct bandgap and direct forbidden transition varying from 1.69 eV to 2.85 eV and 1.62 eV to 1.88 eV, respectively. Further, the variation of (DC) electrical resistivity with temperature (from the room temperature of 27∘C to 350∘C) shows that the electrical resistivity was decreased with increasing temperature indicating a semiconducting transport behavior.
HDAC Inhibition Enhances the In Vivo Efficacy of MEK Inhibitor Therapy in Uveal Melanoma
Authors: Faião-Flores Fernanda , Emmons Michael F. , Durante Michael A. , Kinose Fumi , Saha Biswarup , Fang Bin , Koomen John M. , Chellappan Srikumar P. , Maria-Engler Silvya Stuchi , Rix Uwe , Licht Jonathan D. , Harbour J. William , Smalley Keiran S.M. 
Published: June 2019

Abstract

Purpose:
The clinical use of MEK inhibitors in uveal melanoma is limited by the rapid acquisition of resistance. This study has used multiomics approaches and drug screens to identify the pan-HDAC inhibitor panobinostat as an effective strategy to limit MEK inhibitor resistance.
Experimental Design: Mass spectrometry–based proteomics and RNA-Seq were used to identify the signaling pathways involved in the escape of uveal melanoma cells from MEK inhibitor therapy. Mechanistic studies were performed to evaluate the escape pathways identified, and the efficacy of the MEK-HDAC inhibitor combination was demonstrated in multiple in vivo models of uveal melanoma.

Results:
We identified a number of putative escape pathways that were upregulated following MEK inhibition, including the PI3K/AKT pathway, ROR1/2, and IGF-1R signaling. MEK inhibition was also associated with increased GPCR expression, particularly the endothelin B receptor, and this contributed to therapeutic escape through ET-3–mediated YAP signaling. A screen of 289 clinical grade compounds identified HDAC inhibitors as potential candidates that suppressed the adaptive YAP and AKT signaling that followed MEK inhibition. In vivo, the MEK-HDAC inhibitor combination outperformed either agent alone, leading to a long-term decrease of tumor growth in both subcutaneous and liver metastasis models and the suppression of adaptive PI3K/AKT and YAP signaling.

Conclusions:
Together, our studies have identified GPCR-mediated YAP activation and RTK-driven AKT signaling as key pathways involved in the escape of uveal melanoma cells from MEK inhibition. We further demonstrate that HDAC inhibition is a promising combination partner for MEK inhibitors in advanced uveal melanoma.
Dual Farnesyl and Geranylgeranyl Transferase Inhibitor Thwarts Mutant KRAS-Driven Patient-Derived Pancreatic Tumors
Authors: Kazi Aslamuzzaman , Xiang Shengyan , Yang Hua , Chen Liwei , Kennedy Perry , Ayaz Muhammad , Fletcher Steven , Cummings Christopher , Lawrence Harshani R. , Beato Francisca , Kang Ya'an , Kim Michael P. , Delitto Andrea , Underwood Patrick W. , Fleming Jason B. , Trevino Jose G. , Hamilton Andrew D. , Sebti Said M. 
Published: June 2019

Abstract

Purpose:
Mutant KRAS is a major driver of pancreatic oncogenesis and therapy resistance, yet KRAS inhibitors are lacking in the clinic. KRAS requires farnesylation for membrane localization and cancer-causing activity prompting the development of farnesyltransferase inhibitors (FTIs) as anticancer agents. However, KRAS becomes geranylgeranylated and active when cancer cells are treated with FTIs. To overcome this geranylgeranylation-dependent resistance to FTIs, we designed FGTI-2734, a RAS C-terminal mimetic dual FT and geranylgeranyltransferase-1 inhibitor (GGTI).

Experimental Design:
Immunofluorescence, cellular fractionation, and gel shift assays were used to assess RAS membrane association, Western blotting to evaluate FGTI-2734 effects on signaling, and mouse models to demonstrate its antitumor activity.

Results:
FGTI-2734, but not the selective FTI-2148 and GGTI-2418, inhibited membrane localization of KRAS in pancreatic, lung, and colon human cancer cells. FGTI-2734 induced apoptosis and inhibited the growth in mice of mutant KRAS–dependent but not mutant KRAS–independent human tumors. Importantly, FGTI-2734 inhibited the growth of xenografts derived from four patients with pancreatic cancer with mutant KRAS (2 G12D and 2 G12V) tumors. FGTI-2734 was also highly effective at inhibiting, in three-dimensional cocultures with resistance promoting pancreatic stellate cells, the viability of primary and metastatic mutant KRAS tumor cells derived from eight patients with pancreatic cancer. Finally, FGTI-2734 suppressed oncogenic pathways mediated by AKT, mTOR, and cMYC while upregulating p53 and inducing apoptosis in patient-derived xenografts in vivo.

Conclusions:
The development of this novel dual FGTI overcomes a major hurdle in KRAS resistance, thwarting growth of patient-derived mutant KRAS–driven xenografts from patients with pancreatic cancer, and as such it warrants further preclinical and clinical studies.
Cytotoxic T Cells and their Activation Status are Independent Prognostic Markers in Meningiomas
Authors: Rapp Carmen , Dettling Steffen , Liu Fang , Ull Anna Theresa , Warta Rolf , Jungk Christine , Roesch Saskia , Mock Andreas , Sahm Felix , Schmidt Melissa , Jungwirth Gerhard , Zweckberger Klaus , Lamszus Katrin , Gousias Konstaninos , Kessler Almuth F. , Grabe Niels , Loehr Mario , Ketter Ralf , Urbschat Steffi , Senft Christian , Westphal Manfred , Abdollahi Amir , Debus Juergen , von Deimling Andreas , Unterberg Andreas , Simon Matthias , Herold-Mende Christel C. 
Published: June 2019

Abstract

Purpose:
Clinically aggressive meningiomas (MGMs) are rare but treatment-resistant tumors in need for more effective therapies. Because tumor-infiltrating T lymphocytes (TILs) are essential for successful immunotherapy, we assessed TIL numbers and their activation status in primary (p-) and recurrent (r-) meningiomas and their impact on survival.

Experimental Design:
Presence of TILs was analyzed in 202 clinically well-annotated cases (n = 123 pMGMs and n = 79 rMGMs) focusing on higher-grade meningiomas [n = 97 World Health Organization (WHO) °II, n = 62 WHO°III]. TILs were quantified by a semiautomated analysis on whole-tissue sections stained by multicolor immunofluorescence for CD3, CD8, FOXP3, and programmed cell death protein 1 (PD-1).

Results:
Median T-cell infiltration accounted for 0.59% TILs per total cell count. Although there were no significant WHO°-dependent changes regarding helper (CD3+CD8−FOXP3−) and cytotoxic (CD3+CD8+FOXP3−) TILs in pMGMs, higher number of cytotoxic TILs were associated with an improved progression-free survival (PFS) independent of prognostic confounders. rMGMs were characterized by lower numbers of TILs in general, helper, and cytotoxic TILs. The additional analysis of their activation status revealed that a proportion of PD-1+CD8+ TILs within the TIL population was significantly decreased with higher WHO grade and in rMGMs. Furthermore, lower proportions of PD-1+CD8+ TILs were associated with inferior PFS in multivariate analyses, arguing for PD-1 as activation rather than exhaustion marker.

Conclusions:
We identified higher numbers of CD3+CD8+FOXP3− TILs and proportions of PD-1–expressing CD3+CD8+FOXP3− TILs as novel biomarkers for better survival. These findings might facilitate the selection of patients who may benefit from immunotherapy and argue in favor of an intervention in primary rather than recurrent tumors.