bluuebunny/crossref_metadata_2025 huggingface dataset:
The effects of hyperuricemia on the differentiation and proliferation of osteoblasts and vascular smooth muscle cells are implicated in the elevated risk of osteopenia and vascular calcification in gout: An in vivo and in vitro analysis
Authors: Yan Bing , Liu Dongmei , Zhu Jie , Pang Xiaoling
Published: August 2019

Background

In this study, we established both an animal model and a cellular model of hyperuricemia (HUC). Subsequently, we treated these models with allopurinol (ALLO) to study the effect of uric acid (UA) and ALLO on the differentiation and proliferation of osteoblasts and vascular smooth muscle cells (VSMC).

Methods

Western Blot, immunohistochemistry assay, and real‐time polymerase chain reaction were conducted to measure the changes in the expression of differentiation‐related factors in osteoblasts and VSMCs in HUC and HUC+ALLO groups. MTT (3‐(4,5‐dimethylthiazol‐2‐yl)‐2,5‐diphenyltetrazolium bromide) assay and flow cytometry were utilized to observe the changes in the proliferation of osteoblasts in HUC and HUC+ALLO groups. Von Kossa staining was performed along with calcium content measurement to investigate the effect of HUC/ALLLO on vascular calcification.

Results

In this study, the levels of Wnt3a and differentiation‐related factors, including Runx2, Sp7, Ibsp, Bglap, Dmp1, and Col1a1, were all evidently decreased in HUC rats, while the presence of ALLO increased the levels of above factors. In addition, the viability of osteoblasts was reduced while their apoptosis was elevated in the HUC group, and ALLO treatment reduced the apoptosis and increased the viability of osteoblasts to a certain extent. Moreover, HUC elevated the levels of Wnt3a, Runx2, Sp7, Bglap, Col1a1, SM22a, and Acta2 in VSMCs of HUC rats, leading to greatly increased calcium content and obvious vascular calcification. In contrary, ALLO treatment reduced the effect of HUC. Furthermore, the effect of UA and ALLO on osteoblasts and VSMCs was also validated in cellular models treated with monosodium urate (MSU) crystals or MSU+ALLO.

Conclusions

HUC can suppress the differentiation and proliferation of osteoblasts while promoting the differentiation of VSMCs both in vivo and in vitro. The treatment by ALLO exhibited a therapeutic effect on HUC by promoting the differentiation and proliferation of osteoblasts while reducing vascular calcification.
Inducing differentiation of human urine‐derived stem cells into hepatocyte‐like cells by coculturing with human hepatocyte L02 cells
Authors: Zhou Ming , Shen Liangliang , Qiao Yinggu , Sun Zhenxiao
Published: August 2019

Objectives

To investigate the possibility of inducing differentiation of human urine‐derived stem cells (hUSCs) into hepatocyte‐like cells by coculturing with human hepatocyte L02 cells in vitro.

Methods

HUSCs were isolated from fresh urine samples collected from healthy adult volunteers by centrifugation. Cells were observed under an inverted phase contrast microscope, and proliferative activity was determined by 3‐(4,5‐dimethylthiazol‐2‐yl)‐2,5‐diphenyltetrazolium bromide assay. Stem cell surface markers were detected by flow cytometry. HUSCs were induced to differentiate into hepatocyte‐like cells by coculturing with human hepatocyte L02 cells, which were confirmed by cellular morphology, messenger RNA expression of albumin (ALB), α‐fetoprotein (AFP) and hepatocyte cytochrome P450 (CYP450) analyzed with quantitative reverse transcription polymerase chain reaction and the expression of glycogen detected by glycogen staining kits at 5, 10, and 15 days after coculturing.

Results

HUSCs from urine were successfully isolated and cultured in vitro. At passages 3, the growth curve of hUSCs was S‐shaped with good proliferation activity. Mesenchymal stem cell surface markers CD44 and CD90 were detected positive by flow cytometry. CD31 for endothelial cells and CD34 for hematopoietic stem cell markers were not detected. HUSCs gained the cellular morphology and function of hepatocyte cells including higher expression of several hepatocyte‐specific genes such as ALB and some CYP450, lower expression of AFP and positive glycogen expression (P <
 .05) in coculturing with human hepatocyte L02 cells for 10‐15d.

Conclusions

HUSCs can be induced to differentiate into hepatocyte‐like cells by coculturing with human hepatocyte L02 cells for a certain number of days.
Overexpression of circular RNA circ‐CDC45 facilitates glioma cell progression by sponging miR‐516b and miR‐527 and predicts an adverse prognosis
Authors: Liu Jie , Hou Kuiyuan , Ji Hang , Mi Shan , Yu Guangna , Hu Shaoshan , Wang Jianjiao
Published: August 2019

Glioma (GM) is a highly lethal human cancer. Circular RNAs (circRNAs) act as an imperative factor in oncogenesis. We aimed to investigate the biological functions and mechanisms of circ‐CDC45 in GM. circ‐CDC45 expression in GM specimens and cell lines was measured by real‐time quantitative reverse transcription polymerase chain reaction. Fisher's exact test and Kaplan‐Meier curves further analyzed its clinical implications. A gain/loss‐of‐function study was conducted to investigate the role of circ‐CDC45 in GM. Additionally, luciferase reporter and rescue assays were performed to unravel the mechanisms of circ‐CDC45. High circ‐CDC45 expression was found in GM specimens and cells, which was tightly related to a larger tumor size, higher world health organization (WHO) stages, and worse survival for patients with GM. Functionally, manipulation of circ‐CDC45 expression strongly affected cell growth, apoptosis, migration and invasion, which suggests the oncogenic function of circ‐CDC45 in GM oncogenesis. Stepwise mechanism studies indicated that circ‐CDC45 sponged and regulated the expression of miR‐516b and miR‐527 to promote cell growth and invasion. Briefly, the regulatory network of circ‐CDC45/miR‐516b/miR‐527 plays a pivotal role in GM tumorigenesis and may act as a potential target for GM treatment.
Hypoxia alters the release and size distribution of extracellular vesicles in pancreatic cancer cells to support their adaptive survival
Authors: Patton Mary C. , Zubair Haseeb , Khan Mohammad Aslam , Singh Seema , Singh Ajay P.
Published: August 2019

Pancreatic tumors are highly desmoplastic and poorly‐vascularized, and therefore must develop adaptive mechanisms to sustain their survival under hypoxic condition. Extracellular vesicles (EV) play vital roles in pancreatic tumor pathobiology by facilitating intercellular communication. Here we studied the effect of hypoxia on the release of EVs and examined their role in adaptive survival of pancreatic cancer (PC) cells. Hypoxia promoted the release of EV in PC cell lines, MiaPaCa and AsPC1, wherein former exhibited a far greater induction. Moreover, a time‐dependent, measurable and significant increase was recorded for small EV (SEV) in both the cell lines with only minimal induction observed for medium (MEV) and large EVs (LEV). Similarly, noticeable changes in size distribution of SEV were also recorded with a shift toward smaller average size under extreme hypoxia. Thrombospondin (apoptotic bodies marker) was exclusively detected on LEVs, while Arf6 (microvesicles marker) was mostly present on MEV with some expression in LEV as well. However, CD9 and CD63 (exosome markers) were expressed in both SEV and MEVs with a decreased expression recorded under hypoxia. Among all subfractions, SEV was the most bioactive in promoting the survival of hypoxic PC cells and hypoxia‐inducible factor‐1α stabilization was involved in heightened EV release under hypoxia and for their potency to promote hypoxic cell survival. Altogether, our findings provide a novel mechanism for the adaptive hypoxic survival of PC cells and should serve as the basis for future investigations on broader functional implications of EV.
Identification of human miR‐1839‐5p by small RNA‐seq, a miRNA enriched in neoplastic tissues
Authors: Martínez‐Saucedo Mirna , Bárcenas‐Gómez Yolanda , Baeza‐Capetillo Patricia , Dedden Mark , Aguirre‐Hernandez Jesus , Téllez‐Camacho Samara A. , Sánchez‐Urbina Rocío , Aquino‐Jarquin Guillermo , Granados‐Riveron Javier T.
Published: August 2019

Background

MicroRNAs (miRNAs) modulate gene expression through destabilization or translational inhibition of cytoplasmic transcripts or by transcriptional regulation through binding to genomic DNA. Although miRNAs are globally down‐regulated in cancer, some are overexpressed in neoplastic tissues, playing key roles in tumorigenesis (oncomiRs), sometimes behaving as effective cancer markers.

Methods

Using total RNA from human uterus adenocarcinoma and non‐neoplastic uterus, we conducted a small RNA‐sequencing experiment followed by prediction of novel miRNAs using MirDeep* software. Synteny analysis and whole genome alignments were performed using BLAST. We also evaluated expression by a reverse transcriptase‐polymerase chain reaction (RT‐PCR) in normal tissues of the FSD2 gene, which spans the human miR‐1839‐5p gene in the opposite direction.

Results

MirDeep* analysis predicted a miRNA not previously annotated in databases, identical to and likely the orthologue of mouse miR‐1839‐5p. Whole‐genome local alignments of this miRNA revealed a single perfect hit that is indeed syntenic to mouse miR‐1839‐5p. Alignments with other mammalian orthologues showed considerable conservation. We validated the prediction via a stem‐loop RT‐PCR assay, also employed to screen RNA samples from several additional normal and cancer tissues, showing increased expression in neoplastic tissues compared to their respective non neoplastic counterparts. Human heart tissue expresses both miR‐1839‐5p and FSD2.

Conclusions

Human tissues express an orthologue of mouse miR‐1839‐5p and, given its expression pattern, we suggest that this miRNA could be explored as a potential oncomiR or cancer marker. Also, according to the genomic organization of miR‐1839‐5p and FSD2, perfect complementarity exists between the two elements, making possible miRNA‐directed cleavage in human cardiac tissue.
In vivo evaluation of human patellar tendon microstructure and microcirculation with diffusion MRI
Authors: Wengler Kenneth , Fukuda Takeshi , Tank Dharmesh , Komatsu David E. , Paulus Megan , Huang Mingqian , Gould Elaine S. , Schweitzer Mark E. , He Xiang
Published: August 2019

Background

Patellar tendon (PT) microstructure integrity and microcirculation status play a crucial role in the progression of tendinopathy and tendon repair.

Purpose

To assess the feasibility and robustness of stimulated‐echo based diffusion‐weighted MRI with readout‐segmented echo‐planar imaging (ste‐RS‐EPI) for noninvasive assessment of microstructure and microcirculation of human PT.

Study Type

Prospective.

Subjects

Fifteen healthy volunteers.

Field Strength/Sequence

PT diffusion tensor imaging (DTI) and intravoxel incoherent motion (IVIM) were acquired with an ste‐RS‐EPI protocol on a 3T MRI scanner.

Assessment

Subjects were positioned with their PT at the magic angle. DTI‐derived parameters including axial diffusivity (AD), radial diffusivity (RD), mean diffusivity (MD), and fractional anisotropy (FA) were estimated with b‐values of 0 and 800 s/mm2 and 12 diffusion directions. IVIM‐derived parameters, f
p, D* × f
p, V
b, and D* × V
b were assessed in the central‐third and the outer‐two thirds of the PT with b‐values of 0, 20, 30, 60, 80, 120, 200, 400, and 600 s/mm2 in three orthogonal directions.

Statistical Tests

Paired t‐tests were used to evaluate differences in IVIM parameters between the central‐third and outer‐two thirds regions of the patellar tendon. Paired t‐tests and within‐subject coefficient of variation were used to assess the intra‐ and intersession reproducibility of PT DTI and IVIM parameters.

Results

DTI parameters for healthy PT were 1.54 ± 0.09 × 10‐3 mm2/s, 1.01 ± 0.05 × 10‐3 mm2/s, 1.18 ± 0.06 × 10‐3 mm2/s, and 0.30 ± 0.04 for AD, RD, MD, and FA, respectively. Significantly higher (P < 0.05) IVIM parameters f
p and D* × f
p were observed in the outer‐two thirds (6.1% ± 2.4% and 95.2 ± 49.6, respectively) compared with the central‐third (3.8% ± 2.3% and 48.6 ± 35.2, respectively) of the PT.

Data Conclusion

Diffusion MRI of PT with an ste‐RS‐EPI protocol is clinically feasible. Both DTI‐ and IVIM‐derived parameters of the PT demonstrated good test–retest reproducibility and interrater reliability.

Level of Evidence: 2

Technical Efficacy: Stage 1

J. Magn. Reson. Imaging 2020;51:780–790.
Transformer capacitance matrix computation using 3D boundary element method and adaptive cross approximation
Authors: Drandić Ana , Trkulja Bojan
Published: August 2019

In this paper, a solver based on a 3D boundary element method (BEM) is presented and verified on a transformer geometry. Using a triangular surface mesh of a winding, the unknown charge distribution is found from known potentials of surfaces using the integral equation approach and point matching. The capacitance matrix is calculated from known potentials in nodes of the system. The application of BEM and point‐matching results in a fully populated system matrix. Therefore, a matrix reduction technique adaptive cross approximation (ACA) is employed in order to reduce the CPU time and memory requirements. Both the accuracy of the direct and the accuracy of the ACA approach are benchmarked against the results obtained using the professional finite element method (FEM)‐based software.
Wind speed forecasting based on wavelet transformation and recurrent neural network
Authors: Pradhan Prangya Parimita , Subudhi Bidyadhar
Published: August 2019

With the increase in power demand, renewable energy resources such as wind energy have been developed as one of the fastest growing energy sources. However, the wind power generation system depends on the availability of wind flow. The intermittence nature of wind speed is the most serious concern in wind energy application into the existing power system. Hence, wind speed forecasting approaches are proposed in order to deal with these problems. In this paper, a hybrid model of wind speed forecasting is developed. The proposed hybrid model consists of two steps: the first one is decomposition of wind speed sample data by wavelet technique, and the second step uses these decomposed data to estimate wind speed through recurrent wavelet neural network (RWNN). To validate the proposed model, it is compared with the conventional recurrent neural network (RNN) prediction structure. The obtained results based on real data provide the effectiveness of the proposed model in terms of mean absolute error and the rate of convergence parameter.
Characterization of a new efficient low molecular weight Bacillus subtilis NRC16 levansucrase and its levan
Authors: Salama Bassem M. , Helmy Wafaa A. , Ragab Tamer I. M. , Ali Mamdouh M. , Taie Hanan A. A. , Esawy Mona A.
Published: August 2019

Screening of 18 bacterial honey isolates revealed that all the isolates were levansucrase producers. The most potent isolate that achieved the highest activity (45.66 U/ml) was identified as Bacillus subtilis NRC based on morphological examination and 16S rRNA. The results recorded the necessity of starch (5 g/L), baker's yeast (12.5 g/L), and AlCl3 (5 mM) in improvement of the enzyme productivity. The Bacillus subtilis levansucrase was eluted as a single protein in one purification step. The enzyme molecular weight was (14 kDa). It showed its optimum activity at 45°C and could retain 60% of its activity after incubation at 50°C for 2 h. Its optimum activity was obtained at pH 8.2 and the enzyme showed great pH stability in both acidic and alkaline ranges. Unlike, most levansucrases all tested metals had an adverse effect in enzyme activity. The enzyme had antioxidant activities and were characterized as spherical micro‐ and nanoparticles by transmission electron microscopy. The effect of growth conditions and medium composition in levan structure and its fibrinolytic activity was evaluated.
Expression of plasma membrane H+‐ATPase in cluster roots of white lupin under phosphorus deficiency
Authors: Stein Sophie , Faust Franziska , Jung Stephan , Schubert Sven
Published: August 2019

It was previously shown that plasma membrane (PM) H+‐ATPases of active cluster roots are acclimated to phosphorus (P) deficiency. In the present study, we followed the question whether the qualitative acclimation of PM H+‐ATPase is based on isoform‐specific expression. Therefore, three different PM H+‐ATPase isoforms (LHA1–LHA3) were investigated at the transcriptional level. Our data indicate that LHA1 may play a key role in the qualitative acclimation of PM H+‐ATPase in cluster roots to P deficiency.
Mixed Micellar and Interfacial Studies of Triblock Copolymers with Amphiphilic Drug Ibuprofen in Aqueous Urea Solutions
Authors: Sood Ashwani Kumar , Aggarwal Meenu
Published: August 2019

Mixed micellar and surface properties of non‐ionic triblock copolymers (Pluronic® P123 and F68) and non‐steroidal anti‐inflammatory drug Ibuprofen (IBF) have been evaluated in aqueous urea (100 mM) solutions with the help of surface tension and fluorescence measurements at 298.15 K. Various bulk and surface parameters such as critical micelle concentration (CMC) of the mixtures, micellar mole fraction (X), interaction parameter (β) and free energies were calculated using Clint, Rubingh, Rosen and Maeda models. In aqueous solutions, all the mixtures show synergistic interactions and are more in mixtures of IBF with P123. These interactions decrease in presence aqueous urea solution due to breaking of water structure surrounding the hydrophobic moieties by urea molecules resulting in delayed mixed micellization. Micellar aggregation number (Nagg) obtained from the steady state fluorescence quenching indicate that the participation of triblock copolymer is more than the drug IBF in mixed micelle formation. Stern‐Volmer constant (KSV), dielectric constant (Dexp), and micropolarity (I1/I3) have also been evaluated and their contribution in the mixed micellar systems have been discussed.
Trends in the surgical treatment of pathological proximal femur fractures in the United States
Authors: Varady Nathan H. , Ameen Bishoy T. , Schwab Pierre‐Emmanuel , Yeung Caleb M. , Chen Antonia F.
Published: August 2019

Background and objectives

Large scale data on the treatment of pathologic proximal femur fractures (PPFFs) are lacking. The purpose of this study was to evaluate trends in patient demographics, complication rates, and relative utilization rates of various techniques associated with PPFFs.

Methods

The American College of Surgeons‐National Surgical Quality Improvement Program (NSQIP) database was queried for PPFFs from 2009 to 2017. Patient demographics, 30‐day complications, and utilization rates were recorded. Trends in these variables were determined over the study period.

Results

Most patient demographics did not change during the study period. There were no trends toward decreasing rates of major complications (P = .82), reoperations (P = .65), non‐home discharges (P = .17), readmissions (P = .07), or deaths (P = .75); transfusion rates significantly decreased (P < .001). Rates of hemiarthroplasty decreased (P = .03) and rates of intramedullary nailing increased (P = .001).

Discussion

Despite advances in cancer therapeutics, the average PPFF patient has not significantly changed over the past decade. Similarly, most short‐term outcomes after PPFF surgery have not improved, demonstrating a need for improved perioperative protocols. Finally, rates of IMN fixation are increasing while rates of HA are falling at NSQIP hospitals. Given that orthopedic oncologists favor endoprosthetic reconstruction in most cases, there may be a need for increased communication between orthopedic oncologists and other members of the orthopedic community treating PPFFs.
Grisel's Syndrome in an Adult After Endoscopic Nasopharyngectomy
Authors: Chua Andy J. K. , Tan Bernard W. S. , Tan Tiong Yong , Heah Harold H. W.
Published: August 2019

Background

Grisel's syndrome is rare in adults, and is characterized by nontraumatic atlanto‐axial subluxation secondary to infection. Here, we report a case of Grisel's syndrome occurring after endoscopic nasopharyngectomy.

Methods

A 67‐year‐old man complained of fever and neck pain with reduced lateral rotation after an endoscopic nasopharyngectomy for recurrent nasopharyngeal carcinoma. Flexion and extension X‐rays of the cervical spine demonstrated atlanto‐axial subluxation, and magnetic resonance imaging showed infective changes with cervical osteomyelitis. A diagnosis of Grisel's syndrome with cervical spine osteomyelitis was made. A later computed tomography (CT) scan demonstrated subluxation of C1 on C2, as well as the occipital‐C1 joint.

Results

The patient was treated with intravenous antibiotics and offered surgery for spinal stabilization, but declined. He remained well 15 months post‐op on a cervical collar with minimal pain and no neurologic deficits.

Conclusion

A high index of suspicion for Grisel's syndrome is suggested in patients who have neck pain with reduced range of motion postnasopharyngectomy, and imaging is useful in clinching the diagnosis.

Level of Evidence

4
The effect of creep aging on localized corrosion resistance of AA2060 alloy
Authors: Wang Xun , Zhan Lihua , Liu Chunhui , Ma Peipei , Li He , Hu Libin , Liu Debo , Hu Zhenggen
Published: August 2019

The influence of creep aging at varied stresses on the localized corrosion behavior of AA2060 has been studied in this paper. Samples were subjected to stress free aging (SFA) and creep aging (CA) under two stress levels, after which tensile tests and intergranular corrosion (IGC) tests were carried out. The corrosion morphology and depth were examined using optical microscope. Compared with SFA, CA can enhance the mechanical properties and increase the IGC resistance of Al–Cu–Li alloy but high‐stress CA would intensify the intragranular corrosion penetration in the first 25 hr of aging time. The microstructure observation results show that dislocations introduced by CA provide favorable nucleation sites for T1 precipitates in the grain and impede the growth of T1 precipitates at grain boundary. Therefore, the potential difference between the grain interior and grain boundary can be reduced compared to that for the SFA. The mechanism by which CA affects the corrosion resistance of Al–Cu–Li alloys, as is essential to understand and optimize the creep aging process, has been proposed by considering the effect of creep‐deformation‐induced dislocations.
Detection of microstructural changes of 9% Cr‐martensitic steels during heat treatment and aging by polarization tests
Authors: Schmigalla Sven , Abstoss Kevin G. , Schultze Sabine , Mayr Peter
Published: August 2019

9–12% chromium martensitic steels are widely used as pipe material in steam power plants. Their good creep behavior is based on a finely adjusted microstructure, which is strengthened by precipitates. During long‐term use at higher temperatures degredation mechanisms occur, which affect the initial microstructure. Subgrain and precipitate coarsening as well as phase formation like Laves‐phase ((Fe, Cr)2(Mo, W)) proceed and lead to a reduced creep resistance. For lifetime assessment a nearly nondestructive electrochemical test method would be beneficial to identify microstructural changes during periodical inspections. The paper is focussed on the usability of an adapted electrochemical potentiodynamic reactivation (EPR)‐method and deals with the adjustment of test conditions like electrolyte composition and polarization parameters. The results obtained under optimized test conditions show a clear indication of precipitate formation by changing the characteristics of the EPR‐curves for the well established alloy T/P91 (X10CrMoVNb9‐1) as well as for the boron containing advanced alloy MARBN (X10CrWCoVNb9‐3‐3).
Effects of rare earth elements on corrosion behaviors of low‐carbon steels and weathering steels
Authors: Liu Zheng , Lian Xintong , Liu Tengshi , Yang Yudan , Zhu Jianan , Dong Han
Published: August 2019

The effects of rare earth elements on the corrosion properties of low‐carbon steel and weathering steel were investigated. To elucidate the roles of rare earth elements (Ce and La) and the corrosion behavior of steels, salt spray tests, electrochemical techniques, X‐ray diffractometer, scanning electron microscopy, Electron Probe Micro Analysis (EPMA), and Auger Electron Spectroscopy (AES) were conducted. The results showed that the addition of rare earth elements enhances the corrosion resistance of both low‐carbon steels and weathering steels, indicated by lower corrosion current density and salt spray corrosion rate after rare earth alloying. On the one hand, rare earth elements modify the morphology of inclusions and thus slow down the micro‐area electrochemical corrosion, which improves the electrochemical corrosion resistance of these two steels. On the other hand, rare earth atoms tend to segregate toward the interface between the rust layer and the matrix. Hence, salt spray corrosion resistance is improved due to the enhancement of adhesion and compactness of the rust by the addition of rare earth elements.
PPARA genetic variants increase the risk for cardiac pumping function reductions following acute high‐altitude exposure: A self‐controlled study
Authors: Yang Jie , Liu Chuan , Jihang Zhang , Yu Jie , Dai Limeng , Ding Xiaohan , Qiu Youzhu , Yu Sanjiu , Yang Yuanqi , Wu Yuzhang , Huang Lan
Published: August 2019

Background

Left cardiac pumping function determines the compensatory capacity of the cardiovascular system following acute high‐altitude exposure. Variations in cardiac output (CO) at high altitude are inconsistent between individuals, and genetic susceptibility may play a crucial role. We sought to identify genetic causes of cardiac pumping function variations and describe the genotype–phenotype correlations.

Methods

A total of 151 young male volunteers were recruited and transferred to Lhasa (3,700 m) from Chengdu (<500 m) by plane. Genetic information related to hypoxic signaling and cardiovascular‐related pathways was collected before departure. Echocardiography was performed both before departure and 24 hr after arrival at high altitude.

Results

Here we reported that PPARA variants were closely related to high‐altitude cardiac function. The variants of rs6520015 C‐allele and rs7292407 A‐allele significantly increased the risk for cardiac pumping function reductions following acute high‐altitude exposure. In addition, the individuals carrying haplotypes in PPARA, namely, rs135538 C‐allele, rs4253623 A‐allele, rs6520015 C‐allele and rs7292407 A‐allele (C‐A‐C‐A), suffered a 7.27‐fold risk for cardiac pumping function reduction (95% CI: 2.39–22.15, p = .0006) compared with those carrying the wild‐type haplotype.

Conclusions

This self‐controlled study revealed that PPARA variations significantly increased the risk for cardiac pumping function reductions following acute high‐altitude exposure, providing a potential predictive marker before high‐altitude exposure and targets in mechanistic studies.
Evaluation of Three Embryo Disinfectants on Hatching Success in Four Freshwater Ornamental Fish Species
Authors: Sipos Michael J , Lipscomb Taylor N , Wood Amy L , Ramee Shane W , DiMaggio Matthew A
Published: August 2019

Maintaining optimum conditions for embryo incubation is a critical consideration in finfish aquaculture. To this end, prophylactic disinfectant protocols have been widely used in culture practices for many finfish species. However, empirical evaluations of safety and effectiveness for disinfectants in ornamental fish species are uncommon. We evaluated hatching success in embryos of four ornamental fishes (Redtail Sharkminnow Epalzeorhynchos bicolor, Rainbow Sharkminnow E. frenatum, Featherfin Squeaker Synodontis eupterus, and Blotched Upsidedown Catfish S. nigriventris) after a 15-min immersion in one of three common disinfectant solutions: formalin at 1,500 mg/L, iodine at 100 mg/L, and hydrogen peroxide at 1,000 mg/L. A 15-min immersion in hatching water served as the control. All disinfectants were administered according to either the manufacturer's recommendation or protocols found in published literature for other species. At the tested concentrations, hydrogen peroxide and formalin can be safely used as prophylactic treatments for the majority of species evaluated, with no detrimental effects. In addition, Redtail Sharkminnow embryos treated with formalin exhibited numerically higher hatch success with less variation among replicates than the control treatment. For all species, a 15-min immersion in 100-mg/L iodine resulted in significantly lower hatching success when compared with all other treatments.
Fishery-Scale Discard Mortality Rate Estimate for Haddock in the Gulf of Maine Recreational Fishery
Authors: Capizzano Connor W. , Zemeckis Douglas R. , Hoffman William S. , Benoît Hugues P. , Jones Emily , Dean Micah J. , Ribblett Nate , Sulikowski James A. , Mandelman John W.
Published: August 2019

Empirical discard mortality rate estimates are vital to both stock assessments and fishery management, especially for stocks that experience high discard rates, such as in the recreational rod-and-reel fishery for Haddock Melanogrammus aeglefinus in the Gulf of Maine. The objective of the present study was to derive a fishery-scale discard mortality rate estimate for Haddock that are captured and released in the Gulf of Maine recreational fishery by combining results of an electronic-tagging telemetry experiment with representative fishery-dependent survey data. Scientific personnel and industry partners collected data on a suite of biological, environmental, and technical covariates from 2,442 Haddock caught under authentic fishery scenarios during 2015. Despite being a physoclistous species, <1% of sampled Haddock were observed to die when brought onboard and only ~3% floated upon release. Postrelease fate was then monitored for 154 Haddock using passive acoustic telemetry and determined using a semiquantitative classification procedure reliant upon movement data of Haddock with known fates. The resulting data were analyzed with a parametric survival model to identify which capture-related covariates influenced mortality. Fishing season and length-class of Haddock were the most significant predictors of discard mortality, with increased mortality for smaller individuals caught during the autumn, possibly due to increased temperatures. Survival modeling identified that mortality from these covariates occurred primarily after release as compared with during capture and handling. By integrating survival modeling results with fishery-dependent observations, a fishery-scale discard mortality rate of 63% was estimated for the 2015 fishing year. Based on these findings, we recommend that fishery managers implement measures to reduce recreational Haddock discards, especially of smaller Haddock during warmer months.
Spatial and Temporal Variability in a Large-Reservoir Fish Assessment and Application of a Stratified Random Sampling Approach
Authors: Schall Benjamin J. , Schoenebeck Casey W. , Koupal Keith D.
Published: August 2019

Sampling is often standardized with regard to time and space to monitor population characteristics. Effective sampling of large reservoirs can be complicated by the inherit bias of habitat variability along the reservoir gradient. Our objective was to assess spatial and seasonal distribution patterns of target and nontarget fish species in a large reservoir to identify potential sources of bias. A multitude of fish community and habitat characteristics were measured during seasonal (spring, summer, and fall) gill-net surveys in 2015 and 2016 at Lake McConaughy, Nebraska. Spatial assessments along the longitudinal gradient (up-reservoir to down-reservoir) and between opposing shorelines were made for fish metrics from the seven most common species, and associations between species-specific relative abundance and habitat data were examined. Spatial differences in relative abundance and size structure occurred for nearly all species, with the greatest spatial variability occurring between the upper and lower reservoir zones, but few strong correlations were observed between species-specific relative abundances and habitat data. Seasonal differences occurred in relative abundance and size structure for most species, and size structure was lowest in the fall for most species. To reduce the impact of spatial variability, we determined the minimum required sampling effort to achieve precise estimates of mean catch per net-night using two resampling strategies, with 16 or fewer gill-net sets required for five of seven species and 14 or fewer required if a stratified random approach is utilized. This research quantifies the extent of spatial and temporal variability in standardized sampling on a large reservoir and provides novel insight for managers of similar systems considering a stratified random approach to reduce sampling effort while maintaining desired levels of precision.
Composites of hydrophilic polymers and organic nanocrystals enable enhanced robustness
Authors: Dutta Sounak , Sui XiaoMeng , Weissman Haim , Kalchenko Vyacheslav , Wagner Hanoch Daniel , Rybtchinski Boris
Published: August 2019

We describe a new family of composite materials, polymer/organic nanocrystal (ONC) hybrids. These were prepared from soluble ONCs based on perylene diimides (PDI) and water‐soluble polymers (sodium alginate and polyvinyl alcohol). Polymer/ONC films were characterized by optical spectroscopy, electron microscopy, and tensile strength studies. The films show enhanced chemical and mechanical stability due to synergy between the constituents. The hybrid films are stable in both water and organic solvents, unlike the individual components. The ONCs we employed possess nonlinear optical activity (second harmonic generation, SHG); they showed improved photostability (stable SHG under laser light) in the hybrids. Tensile strength enhancement (as high as twofold in the film having just 2.4% ONCs by weight) was observed as revealed by mechanical measurements. Hybrids with aligned ONCs were also prepared using simple extrusion via syringe needle followed by gelation. Employing ONCs in polymeric hybrid materials enables facile fabrication in aqueous media, synergy, chemical, mechanical, and photostability as well as useful photofunction (SHG), introducing a versatile class of composite materials.
Agreement between self‐reported and registry‐based use of sleep medications and tranquilizers
Authors: Evandt Jorunn , Skurtveit Svetlana , Oftedal Bente , Krog Norun Hjertager , Nafstad Per , Skovlund Eva , Schwarze Per E. , Aasvang Gunn Marit
Published: August 2019

Purpose

The purpose of the present study was to assess the agreement between self‐reported use of sleep medications and tranquilizers and dispensed hypnotics and anxiolytics.

Methods

Self‐reported medication use was obtained from the population‐based survey Health and Environment in Oslo (HELMILO) (2009‐2010) (n = 13 019). Data on dispensed hypnotics and anxiolytics were obtained from the Norwegian Prescription Database (NorPD). As measures of validity, we calculated sensitivity and specificity using both self‐reports and prescription records as the reference standard. Furthermore, we calculated Cohen's kappa. Current self‐reported medication use was compared with prescription data in time windows of both 100 and 200 days preceding questionnaire completion.

Results

The highest sensitivity was observed for current sleep medication use in the 100‐day time window (sensitivity = 0.76, 95% confidence interval [CI]: 0.74, 0.79) when using prescription records as the reference standard. Sensitivity was generally lower for tranquilizers compared with sleep medications. Cohen's kappa showed the highest agreement for the 200‐day time window with substantial agreement for sleep medications (kappa = 0.64; 95% CI: 0.62, 0.67) and moderate agreement for tranquilizers (kappa = 0.45; 95% CI: 0.41, 0.48).

Conclusions

The present study suggests moderate to substantial agreement between self‐reported use of sleep medications and tranquilizers and dispensed drugs in a general adult population. The magnitude of agreement varied according to drug category and time window. Since self‐reported and registry‐based use of these drug classes does not match each other accurately, limitations of each data source should be considered when such medications are applied as the exposure or outcome in epidemiologic studies.
Evaluation of nanocomposites containing graphene nanoplatelets: Mechanical properties and combustion behavior
Authors: Trusiano Giuseppe , Matta Samuele , Bianchi Massimiliano , Rizzi Laura Giorgia , Frache Alberto
Published: August 2019

Polypropylene (PP) nanocomposites containing graphene nanoplatelets (GNPs) with different loadings were fabricated via masterbatch compounding–melt blending processing technique. Morphological studies showed that the method employed provided uniform GNPs dispersion in the matrix, orienting the nanoplatelets along the same direction the flow of matter. Enhancements of storage and Young's modulus occurred, increasing GNP content, and the improvement was more obvious when a compatibilizer, the PP‐grafted‐maleic anhydride, was introduced to achieve a better GNP dispersion and distribution within the matrix. For all the nanocomposites, even for those compatibilized, it was not possible to fully exploit the GNP toughening effect since a stiffening and embrittling effect prevailed. Thermogravimetric analysis showed that GNP incorporation has improved the thermal stability of the nanocomposites. In addition, cone calorimetry results showed that GNPs can act as intumescent flame retardant and significantly reduced the heat release rate, thus improving the flame retardancy of the PP matrix. POLYM. ENG. SCI., 59:2062–2071, 2019. © 2019 Society of Plastics Engineers
Accumulation of “Old Proteins” and the Critical Need for MS‐based Protein Turnover Measurements in Aging and Longevity
Authors: Basisty Nathan , Holtz Anja , Schilling Birgit
Published: August 2019

Aging and age‐related diseases are accompanied by proteome remodeling and progressive declines in cellular machinery required to maintain protein homeostasis (proteostasis), such as autophagy, ubiquitin‐mediated degradation, and protein synthesis. While many studies have focused on capturing changes in proteostasis, the identification of proteins that evade these cellular processes has recently emerged as an approach to studying the aging proteome. With advances in proteomic technology, it is possible to monitor protein half‐lives and protein turnover at the level of individual proteins in vivo. For large‐scale studies, these technologies typically include the use of stable isotope labeling coupled with MS and comprehensive assessment of protein turnover rates. Protein turnover studies have revealed groups of highly relevant long‐lived proteins (LLPs), such as the nuclear pore complexes, extracellular matrix proteins, and protein aggregates. Here, the role of LLPs during aging and age‐related diseases and the methods used to identify and quantify their changes are reviewed. The methods available to conduct studies of protein turnover, used in combination with traditional proteomic methods, will enable the field to perform studies in a systems biology context, as changes in proteostasis may not be revealed in studies that solely measure differential protein abundances.
Anti‐CGRP monoclonal antibodies: breakthrough in migraine therapeutics
Authors: Krishnaswamy Ratna , Malik Bilal Haider , Khan Safeera , Gupta Deepti , Islam Muhammad , Mandal Shrawan Kumar , Rutkofsky Ian H
Published: August 2019

Migraine is considered as one of the most debilitating neurological disorders but the success of the anti‐calcitonin gene‐related peptide (CGRP) therapies marks a new era in the treatment of migraine and has paved way for further research into the exact pathophysiology of migraine. Here, the authors discuss their literature review on the anti‐CGRP therapies to examine the pathophysiology of migraine, with a focus on the possible role of CGRP and the safety and efficacy of monoclonal antibodies targeting it.
The exposome: embrace the complexity
Authors: Greener Mark
Published: August 2019

Links between the microbiome and psychiatric and neurological disease have been the focus of much attention in recent years and may add to our understanding of the complexities of these diseases in tandem with our developing knowledge of the genome's role. However, a third domain ‐ the so‐called exposome ‐ may also need consideration if we are to gain deeper insights into the complex nature of psychiatric and neurological disease.
Phylogenetic spread of sequence data affects fitness of consensus enzymes: Insights from triosephosphate isomerase
Authors: Goyal Venuka Durani , Sullivan Brandon J. , Magliery Thomas J.
Published: August 2019

The concept of consensus in multiple sequence alignments (MSAs) has been used to design and engineer proteins previously with some success. However, consensus design implicitly assumes that all amino acid positions function independently, whereas in reality, the amino acids in a protein interact with each other and work cooperatively to produce the optimum structure required for its function. Correlation analysis is a tool that can capture the effect of such interactions. In a previously published study, we made consensus variants of the triosephosphate isomerase (TIM) protein using MSAs that included sequences form both prokaryotic and eukaryotic organisms. These variants were not completely native‐like and were also surprisingly different from each other in terms of oligomeric state, structural dynamics, and activity. Extensive correlation analysis of the TIM database has revealed some clues about factors leading to the unusual behavior of the previously constructed consensus proteins. Among other things, we have found that the more ill‐behaved consensus mutant had more broken correlations than the better‐behaved consensus variant. Moreover, we report three correlation and phylogeny‐based consensus variants of TIM. These variants were more native‐like than the previous consensus mutants and considerably more stable than a wild‐type TIM from a mesophilic organism. This study highlights the importance of choosing the appropriate diversity of MSA for consensus analysis and provides information that can be used to engineer stable enzymes.
Pharmacokinetics, pharmacodynamics, safety, and immunogenicity of Pelmeg®, a pegfilgrastim biosimilar in healthy subjects
Authors: Roth Karsten , Lehnick Dirk , Wessels Hendrik , Höfler Josef , Gastl Barbara , Jankowsky Ruediger
Published: August 2019

A pharmacokinetics (PK)/pharmacodynamics (PD) study (EudraCT number 2015‐002966‐21) was conducted to investigate the biosimilarity of Pelmeg® (pegfilgrastim), a biosimilar to EU‐authorized Neulasta®, which is used in the clinic for prevention of chemotherapy‐induced neutropenia. The single‐dose, randomized, double‐blind, two‐way crossover study comprised 171 healthy male subjects, receiving Pelmeg and Neulasta (6 mg as subcutaneous injection) in a sequential manner. Primary PK endpoints were the area under the concentration curve from time zero to last measurable concentration (AUC0‐last) and the maximum concentration (Cmax). The primary PD endpoint was the area under the effect curve (AUEC0‐last) for absolute neutrophil count (ANC). Safety and immunogenicity were also assessed. Comparability was demonstrated for both PK endpoints, with geometric mean ratios (test/reference) for AUC0‐last and Cmax of 95.2% and 92.8%, respectively. The corresponding confidence intervals (CIs; 94.3%) were [86.6%;104.7%] for AUC0‐last and [84.4%;102.2%] for Cmax, both being within the equivalence margin of 80.0% to 125.0%. Likewise, PD comparability was demonstrated, with the geometric mean ratio (test/reference) of AUEC0‐last of 100.2%, with a corresponding CI (95%) of 98.7%‐101.8%. No clinically meaningful differences were observed for safety and immunogenicity between Pelmeg and Neulasta. Pelmeg was found to be highly similar to the reference product.
Are cellulose nanocrystals “alien particles” to human experience?
Authors: Piergiovanni Luciano , Fotie Ghislain , Amoroso Luana , Akgun Begum , Limbo Sara
Published: August 2019

A wide family of cellulose‐based additives are authorized worldwide as fillers and thickening agents in foods, pills, and tablets, and microcrystalline cellulose (MCC) is, among these, the most important one. Since MCC manufacturing is similar to the main production route of cellulose nanocrystals (CNCs), it is reasonable to wonder whether the MCC would contain CNCs as minor components. In this Short Communication, we provide first results about the occurrence of CNCs in MCC, observed by dynamic light scattering and transmission electron microscopy after serial filtrations of MCC suspensions. The incidence of cellulose nanoparticles has been proved in several different trials in our ongoing works on diverse MCC samples, and the nanoparticles isolated showed shape and dimensions similar to those commonly produced by acidic hydrolysis at laboratory level. Therefore, the presence of CNCs in many products is considered as a certainty. The foods and the pharmaceuticals we have been consuming so far do indeed contain traces of CNCs to such an extent that this wide presence in consumed products should be taken into account when considering possible limitations of the use of these nanoparticles in food contact materials manufacture.
Aneuploidy and oncoviruses
Authors: Taheri Fateme , Goudarzi Hossein , Faghihloo Ebrahim
Published: August 2019

Seven oncogenic viruses are known for tumorigenesis and contribute to 12% of all human cancers. The oncogenic factors, the target tissue, and pathology of cancer vary among these viruses with several mechanisms proposed for the initiation and development of cancer. Aneuploidy in cells is associated with anomalies in chromosome number that can be a hallmark of cancer, a disease defined by expanded proliferative potential. In this review, we summarize the different mechanisms of aneuploidy and furthermore discuss recent findings of the role of viral oncoproteins in inducing cellular aneuploidy that might facilitate tumorigenesis. Improved understanding of viral oncogenesis may help to find new strategies for controlling virus‐associated cancers.
CLAmp‐seq: A Novel Amplicon‐Based NGS Assay with Concatemer Error Correction for Improved Detection of Actionable Mutations in Plasma cfDNA from Patients with NSCLC
Authors: Wang Lin , Hu Xiaomeng , Guo Qiaomei , Huang Xia , Lin Chia‐Hui , Chen Xiao , Li Min , Yao Qianqian , Zhou Qianjun , Wang Jianmin , Lin Shengrong , Zhao Grace , Weng Li , Qian Kun , Lou Jiatao
Published: August 2019

High‐throughput sequencing of circulating cell‐free DNA (cfDNA) is critical for targeted therapy selection and monitoring in non‐small cell lung cancer (NSCLC) patients. However, low quantities of cfDNA in the blood and assay artifacts limit the sensitivity and specificity of next‐generation sequencing (NGS) test. This study develops a novel amplicon‐based NGS technology, CLAmp‐seq (circular ligation amplification and sequencing), with a concatemer‐based error correction strategy, which effectively removes polymerase errors from the first round of amplification. Analytical validation shows median detection rate of 100% at a mutant allele frequency (MAF) of 0.1% for 20 ng of input. The assay achieves 99.8% and 99.5% concordance of repeatability and reproducibility for 0.1% MAF, respectively, and both 100% for 0.5% MAF cfDNA standards. A comparative analysis of 134 NSCLC patient plasma samples demonstrates strong concordance (97.4%) and linearity (R2 = 0.95) between the CLAmp‐seq NGS readouts and droplet digital PCR (ddPCR) results. The detection of mutants in cfDNA obtained from pretreatment plasma samples shows 94.8% concordance with tissue genotyping results. No mutation is detected in noncancerous control samples. It shows that CLAmp‐seq NGS assay can offer an easy‐to‐use, fast, and accurate molecular diagnostic tool with multiplex capacity that is well‐suited for clinical in vitro diagnosis.