bluuebunny/crossref_metadata_2025 huggingface dataset:
De novo variants in SUPT16H cause neurodevelopmental disorders associated with corpus callosum abnormalities
Authors: Bina Roya , Matalon Dena , Fregeau Brieana , Tarsitano Jacqueline Joani , Aukrust Ingvild , Houge Gunnar , Bend Renee , Warren Hannah , Stevenson Roger E , Stuurman Kyra Eva , Barkovich A James , Sherr Elliott H.
Published: January 2020

Introduction

Whole-exome sequencing (WES) has identified de novo variants in chromatin remodelling genes in patients with neurodevelopmental disorders (NDD). We report on a novel genetic discovery in chromatin remodelling in patients with NDD who also have corpus callosum (CC) anomalies.

Objective

To discover novel genes linked to both CC anomalies and NDD.

Methods

Clinical WES was performed for evaluation of NDD, identifying five patients with de novo variants in SUPT16H, a subunit of the FACT (facilitates chromatin transcription) complex. The clinical phenotypes, genetic results and brain MRIs were obtained and systematically reviewed. In silico protein function predictions were assessed and allele frequencies in control populations were compared.

Results

We identified four patients with de novo missense variants in SUPT16H and one patient with a de novo deletion including SUPT16H. These variants were not reported in the updated Genome Aggregation Database. When assayable, all protein products were predicted to be damaging. Symptoms included intellectual disability, autistic features, minor dysmorphic features and seizures. Anomalies of the CC were seen in all three patients with available brain imaging.

Conclusion

Our findings implicate the gene SUPT16H in a novel disorder characterised by neurodevelopmental deficits and CC anomalies.
Study of collective anisotropies $$v_2$$ and $$v_3$$ and their fluctuations in pA collisions at LHC within a relativistic transport approach
Authors: Sun Yifeng , Plumari Salvatore , Greco Vincenzo
Published: January 2020

We have developed a relativistic transport approach at fixed $$\eta /s(T)$$η/s(T) that incorporates initial space fluctuations generated by wounded quark model to study the hadron observables in 5.02 TeV p + Pb collisions. We find that our approach is able to correctly predict quite well several existing experimental measurements assuming a matter with $$\eta /s=1/4\pi $$η/s=1/4π, a result similar to previous studies within a viscous hydrodynamics approach. Besides, we further discuss the sensitivity of the results on both $$\eta /s(T)$$η/s(T) and the smearing width. Our transport approach has the possibility to include in initial conditions the power law tail associated to minijet, and this improvement extends the agreement with the experimental data to higher $$p_T$$pT ranges. We also perform a comparison to Pb + Pb collisions pointing out that even if the collective flows have a similar magnitude the features of the matter created are different. By studying the correlation between collective flows and initial geometry, we find that the correlation decreases faster in small systems with the increase of n and centrality. In particular we show that the variance of $$\sigma _{v_n}/\langle v_n\rangle $$σvn/⟨vn⟩ has a quite different evolution with centrality for p + Pb, so their measurement could provide some further hint about the correctness of current modelling.
$$\alpha $$-attractor from superconformal E-models in brane inflation
Authors: Sabir Mudassar , Ahmed Waqas , Gong Yungui , Lu Yizhou
Published: January 2020

In the large extra dimensional braneworld inflation, Friedmann equation is modified to include a quadratic term in energy density with an additional parameter $$\lambda $$λ called brane tension in addition to the usual linear term. The high energy brane corrections modify the slow-roll parameters and affect the behaviour of inflation. We analyse the superconformal inflation for E-models and find that there exist $$\alpha $$α-attractors in brane inflation. The predictions for the scalar spectral index $$n_s$$ns and the tensor-to-scalar ratio r are computed numerically, and approximate analytic formulas in the high energy limit have been given for the observable $$n_s$$ns and r. The constraints on the model parameters are obtained by using Planck 2018 and BICEP2 observational data.
Structural balance for discrete-time complex dynamical network associated with the controlled nodes
Authors: Liu Lizhi , Wang Yinhe , Li Xiaoxiao , Gao Zilin
Published: January 2020

In this paper, the discrete-time complex dynamical networks with dynamic weighted value of connection relationships are regarded to be composed of the node and link subsystems, and the state variables of the two subsystems are mutually coupled. Different from most of the existing researches on synchronization or stabilization of nodes, the emphasis of this paper is on the links instead of nodes. This paper mainly focuses on the generation mechanism of structural balance in the link subsystem, the nodes only play an auxiliary role. Associated with the dynamic coupling term in the link subsystem, the suitable controller is proposed for node subsystem such that the structural balance of link subsystem without control input be achieved indirectly. Finally, a numerical simulation is given to show the effectiveness of the method in this paper.
Chapter 5 Paleoproterozoic (1.9–1.8 Ga), syn-orogenic magmatism and sedimentation in the Ljusdal lithotectonic unit, Svecokarelian orogen
Authors: Högdahl Karin , Bergman Stefan
Published: January 2020

Ductile shear zones with dextral transpressive deformation separate the Ljusdal lithotectonic unit from the neighbouring units (Bothnia–Skellefteå and Bergslagen) in the 2.0–1.8 Ga Svecokarelian orogen. Sedimentation steered by regional crustal extension at
c.
1.86–1.83 Ga was sandwiched between two separate phases of ductile strain with crustal shortening and predominantly high-grade metamorphism with plutonic activity. Metamorphism occurred under low-pressure, medium- to high-temperature conditions that locally reached granulite facies. The earlier shortening event resulted in the accretion of outboard sedimentary and
c.
1.89 Ga volcanic rocks (formed in back- or inter-arc basin and volcanic arc settings, respectively) to a continental margin. Fabric development (D
1
), the earlier phase of low-pressure and variable temperature metamorphism (M
1
) and the intrusion of a predominantly granitic to granodioritic batholith with rather high ε
Nd
values (the Ljusdal batholith) occurred along this active margin at 1.87–1.84 Ga. Thrusting with westerly vergence, regional folding and ductile shearing (D
2–3
), the later phase of low-pressure and variable temperature metamorphism (M
2
), and the subsequent minor shear-related intrusion of granite, again with relatively high ε
Nd
values, prevailed at 1.83–1.80 Ga. Mineral deposits include epithermal Au–Cu deposits hosted by supracrustal rocks, V–Fe–Ti mineralization in subordinate gabbro and norite bodies inside the Ljusdal batholith, and graphite in metasedimentary rocks.
Chapter 4 Paleoproterozoic (2.0–1.8 Ga) syn-orogenic sedimentation, magmatism and mineralization in the Bothnia–Skellefteå lithotectonic unit, Svecokarelian orogen
Authors: Skyttä Pietari , Weihed Pär , Högdahl Karin , Bergman Stefan , Stephens Michael B.
Published: January 2020

The Bothnia–Skellefteå lithotectonic unit is dominated by turbiditic wacke and argillite (Bothnian basin), deposited at 1.96 (or older)–1.86 Ga, metamorphosed generally under high-grade conditions and intruded by successive plutonic suites at 1.95–1.93, 1.90–1.88, 1.87–1.85 and 1.81–1.76 Ga. In the northern part, low-grade and low-strain, 1.90–1.86 Ga predominantly magmatic rocks (the Skellefte–Arvidsjaur magmatic province) are enclosed by the basinal components. Subduction-related processes in intra-arc basin and magmatic arc settings, respectively, are inferred. Changes in the metamorphic grade and the relative timing of deformation and structural style across the magmatic province are linked to major shear zones trending roughly north–south and, close to the southern margin, WNW–ESE. Zones trending WNW–ESE and ENE–WSW dominate southwards. Slip along the north–south zones in an extensional setting initiated synchronously with magmatic activity at 1.90–1.88 Ga. Tectonic inversion steered by accretion to a craton to the east, involving crustal shortening, ductile strain and crustal melting, occurred at 1.88–1.85 Ga. Deformation along shear zones under lower-grade conditions continued at
c.
1.8 Ga. Felsic volcanic rocks (1.90–1.88 Ga) host exhalative and replacement-type volcanogenic massive sulphide deposits (the metallogenic Skellefte district). Other deposits include orogenic Au, particularly along the ‘gold line’ SW of this district, porphyry Cu–Au–Mo, and magmatic Ni–Cu along the ‘nickel line’ SE of the ‘gold line’.
Chapter 14 Regional context and lithotectonic framework of the 1.1–0.9 Ga Sveconorwegian orogen, southwestern Sweden
Authors: Stephens Michael B. , Bergström Ulf , Wahlgren Carl-Henric
Published: January 2020

The 1.1–0.9 Ga Sveconorwegian orogen in southwestern Scandinavia belongs to the global system of mountain belts established during the assembly of the supercontinent Rodinia. An overall north–south structural trend and five lithotectonic units bounded by crustal-scale shear zones characterize this orogen. In Sweden, the Eastern Segment abuts the orogen's cratonic foreland eastwards and is separated from the Idefjorden terrane westwards by a ductile shear zone, up to 5 km thick, displaying a sinistral transpressive component. These two lithotectonic units differ on the basis of their pre-Sveconorwegian accretionary tectonic evolution, and the timing of Sveconorwegian high-pressure metamorphism, anatexis and polyphase deformation. High-pressure granulites and migmatites formed at
c.
1.05–1.02 Ga in the Idefjorden terrane; eclogites, high-pressure granulites and migmatites at
c.
0.99–0.95 Ga in the Eastern Segment. Magmatic activity and crustal extension progressed westwards at
c.
0.98–0.92 Ga. Prior to or at 0.93–0.91 Ga, greenschist facies shear deformation with top-to-the-foreland movement affected the frontal part of the orogen. Geodynamic uncertainties concern the affinity of the Idefjorden terrane relative to Fennoscandia (Baltica), the character of the Sveconorwegian orogenesis, and the contiguous or non-contiguous nature of the erosional fronts of the late Mesoproterozoic–early Neoproterozoic orogens in Sweden and Canada.
Chapter 21 Middle thrust sheets in the Caledonide orogen, Sweden: the outer margin of Baltica, the continent–ocean transition zone and late Cambrian–Ordovician subduction–accretion
Authors: Gee David G. , Klonowska Iwona , Andréasson Per-Gunnar , Stephens Michael B.
Published: January 2020

Nappes of continental outer and outermost margin affinities (Middle Allochthon) were transported from locations west of the present Norwegian coast and thrust eastwards onto the Baltoscandian foreland basin and platform. They are of higher metamorphic grade than underlying thrust sheets and most are more penetratively deformed. These allochthons are treated here in three groups. The lower thrust sheets comprise Paleoproterozoic crystalline basement (e.g. Tännäs Augen Gneiss Nappe) and greenschist facies, Neoproterozoic, siliciclastic metasedimentary rocks (e.g. Offerdal Nappe). These are overthrust by a Cryogenian−Ediacaran succession intruded by
c.
600 Ma dolerites (Baltoscandian Dyke Swarm) with an affinity to mid-ocean ridge basalt containing normal to enriched incompatible element contents (Särv Nappes). The upper sheets are dominated by higher-grade allochthons (Seve Nappe Complex) with similar, mainly siliciclastic sedimentary protoliths, more mafic magmatism and some solitary ultramafic bodies. Within this early Ediacaran continent−ocean transition zone (COT) assemblage, generally metamorphosed in amphibolite facies, some nappes experienced migmatization, and eclogites are present. Evidence of ultrahigh-pressure metamorphism has been obtained from garnet peridotites and eclogites; recently, microdiamonds have been discovered in paragneisses. Subduction of the COT started by the late Cambrian and accretion continued through the Ordovician, prior to the Baltica–Laurentia collision. Thrusting of all these Middle allochthons onto the foreland basin exceeds a distance of 400 km.
The Oxygen Reduction and Hydrogen Evolution Reactions on Carbon Supported Cobalt Diselenide Nanostructures
Authors: Campos-Roldán C. A. , Alonso-Vante N.
Published: January 2020

The nanostructured cobalt diselenide (CoSe2) was systematically synthesized onto several chemically modified surface carbon supports. The crystalline structure, morphology and size of synthesized CoSe2 were similar. Oxygen reduction reaction (ORR) and hydrogen evolution reaction (HER) activities were sensitive to the nature of carbon support in acid and alkaline solutions. Both reaction processes were enhanced by the presence of graphitic domains. The electrocatalytic enhancement using chemically modified carbon as a support for cobalt diselenide is discussed.
Review—Recent Advancements in the Utilization of Indium Tin Oxide (ITO) in Electroanalysis without Surface Modification
Authors: Akanda Md. Rajibul , Osman Abdalghaffar Mohammad , Nazal Mazen Khaled , Aziz Md. Abdul
Published: January 2020

Indium tin oxide (ITO), as an electrode, has superiority over metal electrodes commonly used for electroanalysis due to its low cost, low electrochemical background response, wide working potential window, easy surface functionalization and commercial availability. However, researchers have often modified its surface with electron mediators/electrocatalysts to improve its electrocatalytic properties. The modification of the ITO surface with electron mediators/electrocatalysts is tedious, time consuming, and expensive and often suffers from reproducibility problems. As an alternative to this modification step, scientists have tried to develop different strategies to utilize ITO without modification by electron mediators/electrocatalysts. The suitability of bare ITO electrodes i) to obtain potential electrochemical responses from some electroactive species with high signal to noise (S/N) ratios and ii) to possibly improve the S/N ratio with additional signal amplifying systems make it a very lucrative tool for electrochemists. To promote its advancement, it is of great significance to summarize the recent advances and to highlight its excellence in electroanalysis. Thus, this review summarizes literature published up to 2019, focusing specifically on self-electrocatalytic properties of ITO toward suitable electroactive molecules and signal amplification strategies from bare/electroinactive-binder-modified ITO platforms and evaluating their performance in electrochemical sensing. In addition, the review outlines the scope for further research in this context.
Review—Recent Advances in the Development of Nanoporous Au for Sensing Applications
Authors: van der Zalm Joshua , Chen Shuai , Huang Wei , Chen Aicheng
Published: January 2020

In the fields of medicine, environmental protection, and food safety, sensors are imperative for the detection of biomarkers, contaminants, and preservatives. The use of nanoporous gold (NPG) as a sensing platform may greatly enhance performance due to its stability, high surface area, and catalytic abilities. There are many methods reported in the literature for fabricating NPG, including chemical strategies and various electrochemical techniques. The primarily use of NPG in sensing applications may be classified into three categories: electrochemical, bioelectrochemical, and optical. Although both electrochemical and bioelectrochemical sensors are based on the electrical signal produced by a specific analyte, a biological recognition element is involved in the bioelectrochemical sensing process. On the other hand, optical sensors exploit NPG through unique surface plasmon resonance properties that can be monitored by UV-Vis, Raman, or fluorescence spectroscopy. For this review, the primary strategies for fabricating NPG, including dealloying, electrochemical, and dynamic hydrogen bubble template (DHBT), are discussed. In addition, advances made over the last decade towards the detection of biomarkers, pollutants, contaminants, and food additives are highlighted. The future development of NPG based sensors for medical, environmental, and food safety applications is discussed.
Numerical and Experimental Investigation of Air Cooling for Photovoltaic Panels Using Aluminum Heat Sinks
Authors: Arifin Zainal , Tjahjana Dominicus Danardono Dwi Prija , Hadi Syamsul , Rachmanto Rendy Adhi , Setyohandoko Gabriel , Sutanto Bayu
Published: January 2020

An increase in the operating temperature of photovoltaic (PV) panels caused by high levels of solar irradiation can affect the efficiency and lifespan of PV panels. This study uses numerical and experimental analyses to investigate the reduction in the operating temperature of PV panels with an air-cooled heat sink. The proposed heat sink was designed as an aluminum plate with perforated fins that is attached to the back of the PV panel. A comprehensive computational fluid dynamics (CFD) simulation was conducted using the software ANSYS Fluent to ensure that the heat sink model worked properly. The influence of heat sinks on the heat transfer between a PV panel and the circulating ambient air was investigated. The results showed a substantial decrease in the operating temperature of the PV panel and an increase in its electrical performance. The CFD analysis in the heat sink model with an air flow velocity of 1.5 m/s and temperature of 35°C under a heat flux of 1000 W/m2 showed a decrease in the PV panel’s average temperature from 85.3°C to 72.8°C. As a consequence of decreasing its temperature, the heat sink increased the open-circuit photovoltage (VOC) and maximum power point (PMPP) of the PV panel by 10% and 18.67%, respectively. Therefore, the use of aluminum heat sinks could provide a potential solution to prevent PV panels from overheating and may indirectly lead to a reduction in CO2 emissions due to the increased electricity production from the PV system.
Convolutional Neural Network for Breast and Thyroid Nodules Diagnosis in Ultrasound Imaging
Authors: Liang Xiaowen , Yu Jinsui , Liao Jianyi , Chen Zhiyi
Published: January 2020

Objective. The incidence of superficial organ diseases has increased rapidly in recent years. New methods such as computer‐aided diagnosis (CAD) are widely used to improve diagnostic efficiency. Convolutional neural networks (CNNs) are one of the most popular methods, and further improvements of CNNs should be considered. This paper aims to develop a multiorgan CAD system based on CNNs for classifying both thyroid and breast nodules and investigate the impact of this system on the diagnostic efficiency of different preprocessing approaches. Methods. The training and validation sets comprised randomly selected thyroid and breast nodule images. The data were subgrouped into 4 models according to the different preprocessing methods (depending on segmentation and the classification method). A prospective data set was selected to verify the clinical value of the CNN model by comparison with ultrasound guidelines. Diagnostic efficiency was assessed based on receiver operating characteristic (ROC) curves. Results. Among the 4 models, the CNN model using segmented images for classification achieved the best result. For the validation set, the sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), accuracy, and area under the curve (AUC) of our CNN model were 84.9%, 69.0%, 62.5%, 88.2%, 75.0%, and 0.769, respectively. There was no statistically significant difference between the CNN model and the ultrasound guidelines. The combination of the two methods achieved superior diagnostic efficiency compared with their use individually. Conclusions. The study demonstrates the probability, feasibility, and clinical value of CAD in the ultrasound diagnosis of multiple organs. The use of segmented images and classification by the nature of the disease are the main factors responsible for the improvement of the CNN model. Moreover, the combination of the CNN model and ultrasound guidelines results in better diagnostic performance, which will contribute to the improved diagnostic efficiency of CAD systems.
Performance of Novel Engineered Materials from Epoxy Resin with Modified Epoxidized Natural Rubber and Nanocellulose or Nanosilica
Authors: Lanna Aunnuda , Suklueng Montri , Kasagepongsan Chainuson , Suchat Sunisa
Published: January 2020

Performance of new engineered material from epoxy resins with modified epoxidized natural rubber (ENR) and nanofillers were investigated. ENR from renewable natural crop resources is a type of green material with potential to partially substitute or replace and toughen petrochemical-based polymers. Nanocomposites (epoxy resin/ENR/fillers nanoparticles) were characterized with Fourier transform infrared spectroscopy (FTIR), dynamic light scattering (DLS), atomic force microscope (AFM), and scanning electron microscopy (SEM). Comparison of characterized and mechanical properties of nanofiller reinforced with both nanocellulose and nanosilica were studied. The nanocomposites were characterized for their mechanical properties (e.g., impact strength, tensile strength) and thermal degradation behaviour by thermal gravimetric analysis (TGA). Mechanical property investigation results show that, the impact strength of nanocomposites, can be improved by blending in ENR 50 mixed with nanofiller, relative to the baseline nanocomposite mixers. The nanofiller loading in epoxy composite showed the highest improvement in mechanical properties at 0.75 phr (parts per hundred of resin). Effects of accelerated weathering aging were evaluated, and the observed changes were larger with nanosilica than with nanocellulose filler. Here, the accelerated aging increase in tensile properties was found to be 10% after 14 days in both nanofillers, while the other mechanical properties did not change significantly. These nanocomposites are expected to have high wear rates limiting their service life.
Study on Wellbore Temperature and Pressure Distribution in Process of Gas Hydrate Mined by Polymer Additive CO2 Jet
Authors: Wei Minghui , Wu Chenghuai , Zhou Yanxi
Published: January 2020

In order to solve the problem of hydrate reservoir collapse and hydrate regenerated in the process of solid fluidization of natural gas hydrate, a new method of natural gas hydrate exploit by high‐polymer additive (low viscosity carboxymethyl cellulose LV‐CMC) carbon dioxide jet was proposed. The wellbore temperature and pressure changes during this process are analyzed, and the wellbore temperature and pressure model are established and solved by the state space method. This paper also analyzed the effects of relevant parameters on hydrate decomposition, such as injection flow, temperature, and pressure. The results show that increasing the injection pressure allows the hydrate decomposition site to be closer to the annulus outlet. Compared with water, with polymer additive CO2 fluid as the drilling fluid, the intersection point of phase equilibrium curve and annular pressure curve is closer to annular outlet, which is obviously more conducive to well control. In order to avoid phase changes, the injection pressure of the carbon dioxide fluid of the high‐polymer additive should not be lower than 10 MPa, and the injection temperature should not be higher than 285 K.
Machine Learning Supports Long Noncoding RNAs as Expression Markers for Endometrial Carcinoma
Authors: Mello Ana Carolina , Freitas Martiela , Coutinho Laura , Falcon Tiago , Matte Ursula
Published: January 2020

Uterine corpus endometrial carcinoma (UCEC) is the second most common type of gynecological tumor. Several research studies have recently shown the potential of different ncRNAs as biomarkers for prognostics and diagnosis in different types of cancers, including UCEC. Thus, we hypothesized that long noncoding RNAs (lncRNAs) could serve as efficient factors to discriminate solid primary (TP) and normal adjacent (NT) tissues in UCEC with high accuracy. We performed an in silico differential expression analysis comparing TP and NT from a set of samples downloaded from the Cancer Genome Atlas (TCGA) database, targeting highly differentially expressed lncRNAs that could potentially serve as gene expression markers. All analyses were performed in R software. The receiver operator characteristics (ROC) analyses and both supervised and unsupervised machine learning indicated a set of 14 lncRNAs that may serve as biomarkers for UCEC. Functions and putative pathways were assessed through a coexpression network and target enrichment analysis.
Microscopic Positive Tumor Margin Increases Risk for Disease Persistence but Not Recurrence in Patients with Stage T1-T2 Differentiated Thyroid Cancer
Authors: Kamel Hasan Olfat , De Brabandere Sarah , Rachinsky Irina , Laidley David , MacNeil Danielle , Van Uum Stan
Published: January 2020

Introduction. Differentiated thyroid cancer (DTC) has an overall excellent prognosis. Patients who develop recurrent disease have a more unfavorable disease course than those with no recurrence. Higher recurrence rates are seen with incomplete surgical resection and gross positive margins. It is unclear whether microscopic positive margin affects disease recurrence rates as much as grossly positive margin. Aim of the Study. To assess whether microscopic positive margin is an independent predictor of disease recurrence in patients with overall low-risk DTC. Patients and Methods. We conducted a retrospective single-center institutional review of 1,583 consecutive patients’ charts from 1995–2013 using the Canadian Thyroid Cancer Consortium Registry. We included adult patients with nonmetastasizing T1 and T2 DTC with a minimum of three years follow-up. Univariate and multivariate analyses were used to study factors that may influence the risk of persistent/recurrent disease. Strict definitions of persistent versus recurrent disease were applied. Results. 963 patients (152 men and 811 women) were included in the study with a mean age of 46 years. Microscopic positive margins were present in 12% of the specimens and were associated with an increased rate of persistent disease (8% versus 2% in the controls) but not with an increased risk of recurrent disease (1% in both groups). T2 tumors had a significantly higher incidence of positive margins than T1 tumors (48% versus 36%) and significantly higher nodal staging. Conclusions. Microscopic positive margin in the histopathology report in patients with low-risk DTC was associated with a higher rate of persistent disease but did not increase the risk of disease recurrence. A close follow-up of biomarkers and occult residual cancerous lesions is needed, especially in the first year. Further studies are needed to determine whether additional therapeutic measures to prevent recurrence are indicated in T1 and T2 DTC with positive microscopic surgical margins.
Development of a TaqMan Based Real‐Time Fluorescent Quantitative PCR Assay for Detection of Porcine Cytomegalovirus in Semen
Authors: Chen Rujing , Chen Qiuyong , Wu Xuemin , Che Yongliang , Wang Chenyan , Wang Longbai , Yan Shan , Zhou Lunjiang
Published: January 2020

This study described a TaqMan based real‐time fluorescent quantitative PCR (qPCR) method to detect porcine cytomegalovirus (PCMV) infection, targeting the conserved region of the DNA polymerase (DPOL) gene. The standard curve showed a linear regression relationship with a coefficient of 0.999 and a slope of y = −3.249x + 38.958 corresponding to the amplification efficiency at 99.8%. The limit of the qPCR method was 51.9 copies/μl. The established qPCR method showed excellent specificity, with no cross‐reaction observed with common porcine pathogens. The coefficient of variation for intra‐assay and interassay variability ranged up to 1.51% and 2.24%, respectively. PCMV positive signals can be found in semen using this qPCR method, which suggested that we should pay more attention to PCMV contamination in semen in order to eliminate PCMV infection in artificial insemination and xenotransplantation.
Characteristic Features of Electric Fields Radiated by Cloud Flashes in Himalayan Region
Authors: Adhikari Pitri Bhakta , Sharma Shriram
Published: January 2020

Electric fields radiated by cloud flashes that occurred over the rugged terrain of mountainous country Nepal were recorded, analysed, and compared with those from different geographical regions. The total duration of the flash varies from 80 to 469.5 ms. The majority of the cloud flashes were of two stages: the first stage of the majority of the flashes was found to consist of large microsecond scale bipolar pulses having negative initial polarity and the late stage consists of submicrosecond scale pulses having both positive and negative initial polarities. The average durations of the first and second stages are 11.23 and 66.79 ms, respectively, and the time gap between them is 53.57 ms. The cloud pulses led by the negative initial polarity pulses are more compactly distributed and are higher in mountainous countries as compared to those of flashes lead by positive initial polarity pulses, with the average values of interpulse interval being 211.42 and 309.79 μs, respectively.
Serum VEGF: Diagnostic Value of Acute Coronary Syndrome from Stable Angina Pectoris and Prognostic Value of Coronary Artery Disease
Authors: Huang Anan , Qi Xin , Cui Yameng , Wu Yulin , Zhou Shiqi , Zhang Mingyin
Published: January 2020

Background. Although the level of serum vascular endothelial growth factor (VEGF) is elevated in coronary artery disease (CAD) patients, its potential role in acute coronary syndrome (ACS) or stable angina pectoris (SAP) patients remains unclear. Objectives. To evaluate diagnostic accuracy of serum VEGF in determining ACS patients from SAP and analyze the association of serum VEGF with coronary artery lesions in SAP or the GRACE score in ACS, which is involved in the poor prognosis of low serum VEGF. Methods. 248 CAD patients and 48 healthy subjects were enrolled in this study. Serum VEGF levels were detected by using ELISA. The Gensini score or GRACE score was calculated among SAP or ACS patients. All the patients were followed up for a period of 12 months (mean: 10.77 months). Results. VEGF serum concentrations were higher in the ACS subgroup than in the SAP subgroup (P<0.001) with diagnostic accuracy of ACS from SAP (AUC: 0.667, sensitivity: 68.5%, specificity: 60.1%, P<0.001). Patients with high risk of Gensini score showed reduced VEGF levels (P<0.001) accompanied by a negative correlation (r = −0.396, P<0.001). Patients with a higher GRACE score indicated lower VEGF levels (P<0.001). Low serum VEGF was one of the potential risk factors with adjusted HR of 0.531 (P=0.048). Conclusion. Serum VEGF exhibits efficient diagnostic value for detection of ACS from SAP with a cutoff value of 648.75 pg/mL. Low serum VEGF indicates severe coronary artery lesions and a higher GRACE score, which suggests poor clinical outcomes.
Study of the Tensile Damage of 321 Stainless Steel for Solar Thermal Power Generation by Acoustic Emission
Authors: Liao Lida , Tan Qi
Published: January 2020

In this paper, the acoustic emission technique was used to study the signal during the tensile damage of 321 stainless steel for solar thermal power generation. It was found that the peak frequency can effectively distinguish different types of signals during the tensile test. The interference signals generated during the tensile test are effectively resolved by combining the amplitude-peak frequency distribution map and the energy-peak frequency distribution map. The amplitude-time map of the acoustic emission signal is successfully divided into three stages by using peak frequency parameter.
Phase I Study of Trifluridine/Tipiracil Plus Irinotecan and Bevacizumab in Advanced Gastrointestinal Tumors
Authors: Varghese Anna M. , Cardin Dana B. , Hersch Jonathan , Benson Al B. , Hochster Howard S. , Makris Lukas , Hamada Kensuke , Berlin Jordan D. , Saltz Leonard B.
Published: January 2020

Purpose:

This two-part phase Ib trial determined the maximum tolerated dose (MTD) of the combination of trifluridine/tipiracil (FTD/TPI) and irinotecan in patients with advanced gastrointestinal tumors, and evaluated the safety, pharmacokinetics, and antitumor activity of the FTD/TPI, irinotecan, and bevacizumab triplet combination in previously treated metastatic colorectal cancer (mCRC).

Patients and Methods:

Dose escalation (3+3 design) in advanced gastrointestinal tumors was followed by expansion in mCRC. During dose escalation, patients received FTD/TPI (20–35 mg/m2 twice daily; days 1–5 of a 14-day cycle) and irinotecan (120–180 mg/m2; day 1). During expansion, the MTD of FTD/TPI and irinotecan plus bevacizumab (5 mg/kg; day 1) was administered.

Results:

Fifty patients (26 across six dose-escalation cohorts and 24 in the expansion phase) were enrolled. Two dose-limiting toxicities (fatigue and neutropenia) were observed in the dose-escalation phase, and MTD was defined as FTD/TPI 25 mg/m2 twice daily plus irinotecan 180 mg/m2. In the expansion phase, 83% (20/24) experienced any-cause grade ≥3 adverse events (AEs) with the triplet combination, most frequently neutropenia (42%), leukopenia (25%), and diarrhea (12%). AEs of any-cause led to dosing interruptions, modifications, and discontinuations in 29%, 17%, and 4% of patients, respectively. No treatment-related deaths occurred. Three patients (12%) experienced partial responses and 16 (67%) patients had stable disease lasting >4 months. The median progression-free survival was 7.9 months (95% confidence interval, 5.1–13.4 months).

Conclusions:

Tolerability and activity observed in this phase I trial support further investigation of the FTD/TPI–irinotecan–bevacizumab combination in previously treated mCRC.
Trametinib Activity in Patients with Solid Tumors and Lymphomas Harboring BRAF Non-V600 Mutations or Fusions: Results from NCI-MATCH (EAY131)
Authors: Johnson Douglas B. , Zhao Fengmin , Noel Marcus , Riely Gregory J. , Mitchell Edith P. , Wright John J. , Chen Helen X. , Gray Robert J. , Li Shuli , McShane Lisa M. , Rubinstein Larry V. , Patton David , Williams P. Mickey , Hamilton Stanly R. , Conley Barbara A. , Arteaga Carlos L. , Harris Lyndsay N. , O'Dwyer Peter J. , Chen Alice P. , Flaherty Keith T.
Published: January 2020

Purpose:

Substantial preclinical evidence and case reports suggest that MEK inhibition is an active approach in tumors with BRAF mutations outside the V600 locus, and in BRAF fusions. Thus, Subprotocol R of the NCI-MATCH study tested the MEK inhibitor trametinib in this population.

Patients and Methods:

The NCI-MATCH study performed genomic profiling on tumor samples from patients with solid tumors and lymphomas progressing on standard therapies or with no standard treatments. Patients with prespecified fusions and non-V600 mutations in BRAF were assigned to Subprotocol R using the NCI-MATCHBOX algorithm. The primary endpoint was objective response rate (ORR).

Results:

Among 50 patients assigned, 32 were eligible and received therapy with trametinib. Of these, 1 had a BRAF fusion and 31 had BRAF mutations (13 and 19 with class 2 and 3 mutations, respectively). There were no complete responses; 1 patient (3%) had a confirmed partial response (patient with breast ductal adenocarcinoma with BRAF G469E mutation) and 10 patients had stable disease as best response (clinical benefit rate 34%). Median progression-free survival (PFS) was 1.8 months, and median overall survival was 5.7 months. Exploratory subgroup analyses showed that patients with colorectal adenocarcinoma (n = 8) had particularly poor PFS. No new toxicity signals were identified.

Conclusions:

Trametinib did not show promising clinical activity in patients with tumors harboring non-V600 BRAF mutations, and the subprotocol did not meet its primary endpoint.
KLF4 p.A472D Mutation Contributes to Acquired Resistance to Cetuximab in Colorectal Cancer
Authors: Ye Song , Hu Xiaoge , Ni Chao , Jin Weiwei , Xu Yaping , Chang Lianpeng , Zhou Huaixiang , Jiang Jiahong , Yang Liu
Published: January 2020

With the increase of treatment course, resistance to EGFR blockade is inevitable in patients with metastatic colorectal cancer (mCRC). KRAS mutations have been considered to be primary drivers of this resistance; however, the potential function of other genes has not been extensively investigated. This study collected 17 plasma samples from patients with mCRC with cetuximab resistance, and target-capture deep sequencing was used to identify mutations in circulating tumor DNA (ctDNA). Analysis of mutational prevalence in ctDNA was performed from three colorectal cancer tissue-based datasets and one ctDNA dataset. The prevalence of mutations identified in ctDNA was consistent with both colorectal cancer tissue-based and ctDNA datasets. Clonal analysis revealed that 41.2% of patients were positive for at least one subclone. Multiple mechanisms of cetuximab resistance were coexisted in individual patients, and one of the patients even harbored nine distinct mutations. In particular, functional study of Krüppel-like factor 4 (KLF4) p.A472D revealed increased cetuximab resistance in colorectal cancer cells, which was associated with the increased phosphorylation of downstream EGFR signaling proteins. These results suggest that KLF4 p.A472D may contribute to cetuximab resistance in patients with mCRC and thus may serve as a new biomarker in clinical application. Monitoring somatic mutations related to cetuximab resistance in patients with mCRC through ctDNA may provide real-time insights for clinical reference and treatment planning.
Preclinical Activity of Ribociclib in Squamous Cell Carcinoma of the Head and Neck
Authors: van Caloen Gabrielle , Schmitz Sandra , El Baroudi Mariama , Caignet Xavier , Pyr dit Ruys Sébastien , Roger Pierre P. , Vertommen Didier , Machiels Jean-Pascal
Published: January 2020

Cell-cycle pathway impairments resulting in CDK4 and 6 activation are frequently observed in human papillomavirus (HPV)-negative squamous cell carcinoma of the head and neck (SCCHN). We investigated the activity of ribociclib, a CDK4/6 inhibitor, in SCCHN models with the aim of identifying predictive biomarkers of response. HPV-negative or HPV-positive SCCHN cell lines (n = 8) and patient-derived tumor xenograft (PDTX) models (n = 6) were used. The models were classified according to their sensitivity to ribociclib to investigate potential predictive biomarkers. Ribociclib had a cytostatic effect in some HPV-negative SCCHN models but had no effect in HPV-positive models. In SCCHN cell lines and PDTXs, the retinoblastoma (Rb) protein expression level correlated with ribociclib activity. Rb knockdown was, however, not sufficient to block G0–G1 arrest induced by ribociclib in Detroit-562 where p107, p130, and Forkhead BOX M1 (FOXM1) were also implicated in ribociclib activity. Cell lines harboring epithelial-to-mesenchymal transition (EMT) features were less sensitive to ribociclib than those with an epithelial phenotype. Rb downregulation induced EMT in our Rb-expressing SCCHN cell lines. However, ribociclib still had significant activity in one PDTX model with high Rb and vimentin expression, suggesting that the presence of vimentin alone is not enough to induce ribociclib resistance. These findings suggest that CDK4/6 inhibitors should be investigated in patients with HPV-negative SCCHN with high Rb expression and an epithelial phenotype. Although these biomarkers are not predictive in all cases, they may enrich the population that could benefit from CDK4/6 inhibitors.
Combining Serum Cystatin C and Urinary N-Acetyl-Beta-D-Glucosaminidase Improves the Precision for Acute Kidney Injury Diagnosis after Resection of Intracranial Space-Occupying Lesions
Authors: Deng Yujun , Ma Jianchao , Hou Yating , Zhou Dong , Hou Tieying , Li Jinghua , Liang Silin , Tan Ning , Chen Chunbo
Published: January 2020

Background: Postoperative acute kidney injury (AKI) is frequent and associated with adverse outcomes. Unfortunately, the early diagnosis of AKI remains a challenge. Combining functional and tubular damage biomarkers may provide better precision for AKI detection. However, the diagnostic accuracy of this combination for AKI after neurosurgery is unclear. Serum cystatin C (sCysC) and urinary albumin/creatinine ratio (uACR) are considered functional biomarkers, while urinary N-acetyl-β-D-glucosaminidase (uNAG) represents tubular damage. We aimed to assess the performances of these clinical available biomarkers and their combinations for AKI prediction after resection of intracranial space-occupying lesions. Methods: A prospective study was conducted, enrolling adults undergoing resection of intracranial space-occupying lesions and admitted to the neurosurgical intensive care unit. The discriminative abilities of postoperative sCysC, uNAG, uACR, and their combinations in predicting AKI were compared using the area under the receiver operating characteristic curve (AUC-ROC), continuous net reclassification index (cNRI), and incremental discrimination improvement (IDI). Results: Of 605 enrolled patients, AKI occurred in 67 patients. The cutoff values of sCysC, uNAG, and uACR to predict postoperative AKI were 0.72 mg/L, 19.98 U/g creatinine, and 44.21 mg/g creatinine, respectively. For predicting AKI, the composite of sCysC and uNAG (AUC-ROC = 0.785) outperformed either individual biomarkers or the other two panels (uNAG plus uACR or sCysC plus uACR). Adding this panel to the predictive model improved the AUC-ROC to 0.808. Moreover, this combination significantly improved risk reclassification over the clinical model alone, with cNRI (0.633) and IDI (0.076). Superior performance of this panel was further confirmed with bootstrap internal validation. Conclusions: Combination of functional and tubular damage biomarkers improves the predictive accuracy for AKI after resection of intracranial space-occupying lesions.
Treatment of Renal Anemia with Roxadustat: Advantages and Achievement
Authors: Li Zuo-Lin , Tu Yan , Liu Bi-Cheng
Published: January 2020

Background: Although renal anemia has attracted widespread attention, a large proportion of chronic kidney disease (CKD) patients with anemia still do not meet the hemoglobin (Hb) targets. The discovery of prolyl hydroxylase domain (PHD) enzymes as regulators of hypoxia-inducible factor (HIF)-dependent erythropoiesis has led to the development of novel therapeutic agents for renal anemia. Roxadustat, the first small-molecule HIF-PHD inhibitor, has completed the phase 3 trials. There are currently more than 15 phase 3 clinical trials worldwide assessing the efficacy and safety of roxadustat in CKD patients with anemia. This review will summarize recent findings of roxadustat in the treatment of renal anemia. Summary: Although the administration of erythropoiesis-stimulating agents (ESAs) and iron supplementation are a well-established and highly effective therapeutic approach for renal anemia, there are several safety concerns. Current findings from phase 2 and 3 trials suggest that roxadustat is clinically effective and well tolerated. On the one hand, roxadustat could increase endogenous erythropoietin (EPO) levels within or near physiological range in a titratable manner by inducing HIF pathway activation transiently. On the other hand, roxadustat also improves iron metabolism by decreasing serum hepcidin and increasing intestinal iron absorption, which is beneficial to functional iron deficiency and absolute iron deficiency. More importantly, the erythropoietic response of roxadustat is independent of baseline inflammatory state of CKD patients. Thus, the discovery of roxadustat will revolutionize the treatment strategy for renal anemia. Key Messages: Roxadustat is an emerging and promising therapeutic approach against anemia in CKD patients, which differs from those of conventional ESAs. Roxadustat corrects anemia of CKD patients through multiple pathways, beyond elevating EPO levels within physiological range, and also by handling iron metabolism (particularly decreasing the hepcidin levels). Furthermore, the Hb response of roxadustat is independent of the inflammatory microenvironment.
Effects of Cycloleucine in the Nucleus Accumbens Septi on the Elevated plus Maze Test in Rats
Authors: Gargiulo Augusto P.I. , Acuña Andrés , Gargiulo Mercedes M.L. , Gargiulo Ángel J.M. , Gargiulo Marcos C.J. , Baiardi Gustavo C. , Mora Sergio , Lafuente José Vicente , Romanowicz Esteban , Landa Adriana I. , Guevara Manuel A. , Gargiulo Pascual Ángel
Published: January 2020

Introduction: In recent years, an important number of studies have emphasized the psychopharmacological actions of cycloleucine (1-aminocyclopentanecarboxylic acid) acting on the NR1 subunit (glycine allosteric site) of NMDA (N-methyl-D-aspartic acid) receptor. We studied the effects of its injection in an anxiety test. Methods: The elevated plus maze test was used. Male rats bilaterally cannulated into the nucleus accumbens septi (NAS) were employed. Rats were divided into 5 groups that received either 1 µL injections of saline or cycloleucine (0.5, 1, 2, or 4 µg) 15 min before testing. Results: Time spent in the open arm was significantly increased by cycloleucine treatment with all doses (1 and 2 µg, p < 0.05; 0.5 and 4 µg, p < 0.01), like number of extreme arrivals (0.5 and 1 µg, p < 0.05; 2 µg, p < 0.01; and 4 µg, p < 0.001). Open arm entries were increased by the highest dose only (4 µg, p < 0.01). Discussion/Conclusion: Present results show no difference between all doses in the time spent in the open arm, suggesting an indirect, noncompetitive action of the drug. The increase in extreme arrivals and open arm entries suggests a dose influence in these parameters. We conclude that cycloleucine influence on the NMDA receptors within NAS leads to anxiolytic-like effects and behavioral disinhibition, which once more confirms the involvement of NAS in anxiety processing.
Unique Case of a Tenth Cesarean Section in an Emirati Woman
Authors: Hassan Ikram Abdelaziz Salih , Hamza Lama Khalid
Published: January 2020

Cesarean deliveries have risen significantly over the past few decades due to advanced maternal age, defensive obstetric practice, medico-legal concerns, and maternal request. A cesarean section is a life-saving surgical procedure when certain complications arise during pregnancy and labor. However, it is a major surgery and is associated with immediate maternal and perinatal risks and may have implications for future pregnancies as well as long-term effects that are still being investigated. A major obstetric hazard of repeat cesarean section is the increased risk of uterine scar rupture during pregnancy resulting in high fetal and maternal morbidity and mortality. Also, there are increased risks associated with placenta previa and placenta accreta spectrum. We present a unique case of a woman who underwent her 10th cesarean section which was uncomplicated.
O processo como obra
Authors: Néia Lucas Martins
Published: January 2020

Este artigo propõe uma análise interartes do documentário Moscou (2009), no qual Eduardo Coutinho apresenta o processo de criação de uma montagem da peça As três irmãs, de Anton Tchekhov, com atores do Grupo Galpão dirigidos por Enrique Diaz. O trabalho evoca conexões entre tradição e contemporaneidade ao traçar um percurso desde a escrita da peça – bem como sua primeira montagem – na Rússia do início dos anos 1900 até a cena cultural brasileira da década de 2000. Desta forma, estabelecemos um diálogo entre teóricos do teatro – do drama e da cena –, do cinema e dos processos de criação. Observamos, por fim, que o documentário, ao se contaminar com a manifestação teatral e com a ideia de work in progress, atua como um “caderno de registros” e território de inscrição das poéticas de Tchekhov, de Diaz, de Coutinho e dos atores do Grupo Galpão, circunscritas pela problemática do tempo.