bluuebunny/crossref_metadata_2025 huggingface dataset:
Alternative Pedicle Screw Design via Biomechanical Evaluation
Authors: Kwon Jiwoon , Ha Myung Heon , Lee Moon Gu
Published: July 2020

With the recent increase in the elderly population, many people suffer from spinal diseases, and, accordingly, spinal fusion surgery using pedicle screws has been widely applied to treat them. However, most research on pedicle screw design has been focused on the test results rather than the behavior of the screws and vertebrae. In this study, a design platform with a series of biomechanical tests and analyses were presented for pedicle screw improvement and evaluation. The platform was then applied to an alternative hybrid screw design with quadruple and double threads. An experimental apparatus was developed to investigate the bending strength of the screw, and several tests were performed based on the ASTM F1717 standard. In the experiments, it was confirmed that the alternative pedicle screw has the highest bending strength. To examine the stress distribution of pedicle screws, finite element models were established, through which it was found that the proposed pedicle screw has sufficient mechanical safety to make it acceptable for spinal fusion treatment. Finally, we conclude that the platform has good potential for the design and evaluation of pedicle screws, and the alternative dual screw design is one of the best options for spinal fusion surgery.
On-Off Control Strategy in a BWRO System under Variable Power and Feedwater Concentration Conditions
Authors: Ruiz-García A. , Nuez I.
Published: July 2020

Although reverse osmosis (RO) is the technology of choice for solving water shortage problems, it is a process that consumes large amounts of energy. Brackish water (BW) desalination is more efficient than seawater desalination due to the lower salinity of the feedwater source. This makes coupling renewable energy sources with BWRO systems attractive. The operation of this type of systems is complex and requires the design of control strategies to obtain optimal operation. The novelty of this work was to propose a simple on-off control strategy for operating a BWRO system that can work with one and two stages and with different configurations considering six spiral wound membrane elements per pressure vessel (PV). The feedwater quality variations of a real groundwater well were used together with a computational tool to simulate the response of the different configurations with the purpose of selecting the most appropriate depending on the input power to the BWRO system. The most suitable configurations were found to be 1:0, 2:1 and 3:2 (PV first stage:PV second stage). It was additionally found that increased feedwater concentrations resulted in shorter operating ranges to maximize permeate water production for the 1:0 and 2:1 configurations, and that the 3:2 configuration was the most suitable for most of the operating range.
Measurement Uncertainty Analysis of a Stitching Linear-Scan Method for the Evaluation of Roundness of Small Cylinders
Authors: Li Qiaolin , Shimizu Yuki , Saito Toshiki , Matsukuma Hiraku , Gao Wei
Published: July 2020

Influences of angular misalignments of a small cylinder on its roundness measurement by the method referred to as the stitching linear scan method are theoretically investigated. To compensate for the influences, a technique for measuring angular misalignments of a small cylinder by utilizing the linear-scan surface form stylus profilometer, which is employed for roundness measurement, is newly proposed. In addition, for roundness measurement, a holder unit capable of compensating for the angular misalignments of a small cylinder is developed, and the feasibility of the proposed technique is verified in experiments. Furthermore, a measurement uncertainty analysis of the stitching linear-scan method is carried out through numerical calculations based on a Monte Carlo method.
Effect of Daily Intake of a Saffron Infusion on Blood Cholesterol Levels
Authors: Bagur M. José , Alonso Salinas Gonzalo L. , Jiménez-Monreal Antonia M. , Serrano-Heras Gemma , Martínez-Tomé. Magdalena , Alonso Gonzalo L.
Published: July 2020

Saffron (Crocus sativus L.), as well as having notable culinary value, has been traditionally used as a medicinal plant due to its bioactivity. Furthermore, its antioxidant properties have been evaluated, and it may have cardiovascular benefits. Multiple sclerosis (MS) is a chronic disease of the central nervous system that causes a diminution in the daily physical exercise of patients. This sedentary lifestyle may contribute to an increased incidence of dyslipidaemia in this population, and could explain the increased cardiovascular morbidity. The aim of this study was to assess the effect of the intake of a saffron infusion over 96 days on the lipid profile of MS patients. Considering the extraction kinetics of bioactive metabolites, the best way to prepare the infusion was by using ground saffron (PDO “Azafrán de La Mancha”), passed through a 0.5 mm sieve and infused with water at the boiling point (95–100 °C). A total of 35 MS patients took a midafternoon infusion for 96 days; 16 of them completed the treatment. A significant decrease in total blood cholesterol levels from 199.5 to 179.5 mg/dL was observed. Additionally, a significant diminution of triglyceride levels, from 124.0 to 101.0 mg/dL, was observed. In conclusion, the intake of an infusion of 50 mg of “Azafrán de La Mancha” for 96 days had a lipid-lowering effect in patients with MS.
A New Background Method for Greenhouse Gases Flux Calculation Based in Back-Trajectories Over the Amazon
Authors: Gatti Domingues Lucas , Vanni Gatti Luciana , Aquino Afonso , Sánchez Alber , Correia Caio , Gloor Manuel , Peters Wouter , Miller John , Turnbull Jocelyn , Santana Ricardo , Marani Luciano , Câmara Gilberto , Neves Raiane , Crispim Stéphane
Published: July 2020

The large amount of carbon stored in trees and soils of the Amazon rain forest is under pressure from land use as well as climate change. Therefore, various efforts to monitor greenhouse gas exchange between the Amazon forest and the atmosphere are now ongoing, including regular vertical profile (surface to 4.5 km) greenhouse gas measurements across the Amazon. These profile measurements can be used to calculate fluxes to and from the rain forest to the atmosphere at large spatial scales by considering the enhancement or depletion relative to the mole fraction of air entering the Amazon basin from the Atlantic, providing an important diagnostic of the state, changes and sensitivities of the forests. Previous studies have estimated greenhouse gas mole fractions of incoming air (‘background’) as a weighted mean of mole fractions measured at two background sites, Barbados (Northern Hemisphere) and Ascension (Southern hemisphere) in the Tropical Atlantic, where the weights were based on sulphur hexafluoride (SF6) measured locally (in the Amazon vertical profiles) and at the two background sites. However, this method requires the accuracy and precision of SF6 measurements to be significantly better than 0.1 parts per trillion (picomole mole−1), which is near the limit for the best SF6 measurements and assumes that there are no SF6 sources in the Amazon basin. We therefore present here an alternative method. Instead of using SF6, we use the geographical position of each air-mass back-trajectory when it intersects the limit connecting these two sites to estimate contributions from Barbados versus Ascension. We furthermore extend the approach to include an observation site further south, Cape Point, South Africa. We evaluate our method using CO2 vertical profile measurements at a coastal site in Brazil comparing with values obtained using this method where we find a high correlation (r2 = 0.77). Similarly, we obtain good agreement for CO2 background when comparing our results with those based on SF6, for the period 2010–2011 when the SF6 measurements had excellent precision and accuracy. We also found high correspondence between the methods for background values of CO, N2O and CH4. Finally, flux estimates based on our new method agree well with the CO2 flux estimates for 2010 and 2011 estimated using the SF6-based method. Together, our findings suggest that our trajectory-based method is a robust new way to derive background air concentrations for the purpose of greenhouse gas flux estimation using vertical profile data.
Mapping of Recognition Sites of Monoclonal Antibodies Responsible for the Inhibition of Pneumolysin Functional Activity
Authors: Kucinskaite-Kodze Indre , Simanavicius Martynas , Dapkunas Justas , Pleckaityte Milda , Zvirbliene Aurelija
Published: July 2020

The pathogenicity of many bacteria, including Streptococcus pneumoniae, depends on pore-forming toxins (PFTs) that cause host cell lysis by forming large pores in cholesterol-containing cell membranes. Therefore, PFTs-neutralising antibodies may provide useful tools for reducing S. pneumoniae pathogenic effects. This study aimed at the development and characterisation of monoclonal antibodies (MAbs) with neutralising activity to S. pneumoniae PFT pneumolysin (PLY). Five out of 10 produced MAbs were able to neutralise the cytolytic activity of PLY on a lung epithelial cell line. Epitope mapping with a series of recombinant overlapping PLY fragments revealed that neutralising MAbs are directed against PLY loops L1 and L3 within domain 4. The epitopes of MAbs 3A9, 6E5 and 12F11 located at L1 loop (aa 454–471) were crucial for PLY binding to the immobilised cholesterol. In contrast, the MAb 12D10 recognising L3 (aa 403–423) and the MAb 3F3 against the conformational epitope did not interfere with PLY-cholesterol interaction. Due to conformation-dependent binding, the approach to use overlapping peptides for fine epitope mapping of the neutralising MAbs was unsuccessful. Therefore, the epitopes recognised by the MAbs were analysed using computational methods. This study provides new data on PLY sites involved in functional activity.
Cold Atmospheric Plasma Is a Potent Tool to Improve Chemotherapy in Melanoma In Vitro and In Vivo
Authors: Alimohammadi Mina , Golpour Monireh , Sohbatzadeh Farshad , Hadavi Seyedehniaz , Bekeschus Sander , Niaki Haleh Akhavan , Valadan Reza , Rafiei Alireza
Published: July 2020

Malignant melanoma is a devastating disease. Because of its aggressiveness, it also serves as a model tumor for investigating novel therapeutic avenues. In recent years, scientific evidence has shown that cold atmospheric plasma (CAP) might be a promising modality in cancer therapy. In this study, we aimed to evaluate the effect of CAP generated by an argon plasma jet alone or in combination with dacarbazine (DAC) on melanoma cells in vitro and in vivo. The effects of the CAP on inducing lipid peroxidation and nitric oxide production were higher in B16 melanoma cells in comparison to non-malignant L929 cells. Assays on cell growth, apoptosis, and expression of genes related to, e.g., autophagic processes, showed CAP to have a substantial impact in melanoma cells while there were only minoreffects in L929 cells. In vivo, both CAP monotherapy and combination with DAC significantly decreased tumor growth. These results suggest that CAP not only selectively induces cell death in melanoma but also holds promises in combination with chemotherapy that might lead to improved tumor control.
Nerve Segmentation with Deep Learning from Label-Free Endoscopic Images Obtained Using Coherent Anti-Stokes Raman Scattering
Authors: Yamato Naoki , Matsuya Mana , Niioka Hirohiko , Miyake Jun , Hashimoto Mamoru
Published: July 2020

Semantic segmentation with deep learning to extract nerves from label-free endoscopic images obtained using coherent anti-Stokes Raman scattering (CARS) for nerve-sparing surgery is described. We developed a CARS rigid endoscope in order to identify the exact location of peripheral nerves in surgery. Myelinated nerves are visualized with a CARS lipid signal in a label-free manner. Because the lipid distribution includes other tissues as well as nerves, nerve segmentation is required to achieve nerve-sparing surgery. We propose using U-Net with a VGG16 encoder as a deep learning model and pre-training with fluorescence images, which visualize the lipid distribution similar to CARS images, before fine-tuning with a small dataset of CARS endoscopy images. For nerve segmentation, we used 24 CARS and 1,818 fluorescence nerve images of three rabbit prostates. We achieved label-free nerve segmentation with a mean accuracy of 0.962 and an F 1 value of 0.860. Pre-training on fluorescence images significantly improved the performance of nerve segmentation in terms of the mean accuracy and F 1 value ( p < 0.05 ). Nerve segmentation of label-free endoscopic images will allow for safer endoscopic surgery, while reducing dysfunction and improving prognosis after surgery.
Metabolic Roles of Plant Mitochondrial Carriers
Authors: Fernie Alisdair , Cavalcanti João , Nunes-Nesi Adriano
Published: July 2020

Mitochondrial carriers (MC) are a large family (MCF) of inner membrane transporters displaying diverse, yet often redundant, substrate specificities, as well as differing spatio-temporal patterns of expression; there are even increasing examples of non-mitochondrial subcellular localization. The number of these six trans-membrane domain proteins in sequenced plant genomes ranges from 39 to 141, rendering the size of plant families larger than that found in Saccharomyces cerevisiae and comparable with Homo sapiens. Indeed, comparison of plant MCs with those from these better characterized species has been highly informative. Here, we review the most recent comprehensive studies of plant MCFs, incorporating the torrent of genomic data emanating from next-generation sequencing techniques. As such we present a more current prediction of the substrate specificities of these carriers as well as review the continuing quest to biochemically characterize this feature of the carriers. Taken together, these data provide an important resource to guide direct genetic studies aimed at addressing the relevance of these vital carrier proteins.
The Interaction of Temozolomide with Blood Components Suggests the Potential Use of Human Serum Albumin as a Biomimetic Carrier for the Drug
Authors: Rubio-Camacho Marta , Encinar José A. , Martínez-Tomé María José , Esquembre Rocío , Mateo C. Reyes
Published: July 2020

The interaction of temozolomide (TMZ) (the main chemotherapeutic agent for brain tumors) with blood components has not been studied at the molecular level to date, even though such information is essential in the design of dosage forms for optimal therapy. This work explores the binding of TMZ to human serum albumin (HSA) and alpha-1-acid glycoprotein (AGP), as well as to blood cell-mimicking membrane systems. Absorption and fluorescence experiments with model membranes indicate that TMZ does not penetrate into the lipid bilayer, but binds to the membrane surface with very low affinity. Fluorescence experiments performed with the plasma proteins suggest that in human plasma, most of the bound TMZ is attached to HSA rather than to AGP. This interaction is moderate and likely mediated by hydrogen-bonding and hydrophobic forces, which increase the hydrolytic stability of the drug. These experiments are supported by docking and molecular dynamics simulations, which reveal that TMZ is mainly inserted in the subdomain IIA of HSA, establishing π-stacking interactions with the tryptophan residue. Considering the overexpression of albumin receptors in tumor cells, our results propose that part of the administered TMZ may reach its target bound to plasma albumin and suggest that HSA-based nanocarriers are suitable candidates for designing biomimetic delivery systems that selectively transport TMZ to tumor cells.
Alternaria alternata Toxins Synergistically Activate the Aryl Hydrocarbon Receptor Pathway In Vitro
Authors: Hohenbichler Julia , Aichinger Georg , Rychlik Michael , Del Favero Giorgia , Marko Doris
Published: July 2020

Alternaria molds simultaneously produce a large variety of mycotoxins, of which several were previously reported to induce enzymes of phase I metabolism through aryl hydrocarbon receptor activation. Thus, we investigated the potential of naturally occurring Alternaria toxin mixtures to induce Cytochrome P450 (CYP) 1A1/1A2/1B1 activity. Two variants of an extract from cultured Alternaria alternata, as well as the toxins alternariol (AOH), alternariol monomethyl ether (AME), altertoxin I (ATX-I), and altertoxin II (ATX-II), were tested singularly and in binary mixtures applying the 7-ethoxy-resorufin-O-deethylase (EROD) assay in MCF-7 breast cancer cells. Sub-cytotoxic concentrations of the two toxin mixtures, as well as ATX-I, ATX-II and AOH, exhibited dose-dependent enhancements of CYP 1 activity. ATX-I and ATX-II interacted synergistically in this respect, demonstrating the two perylene quinones as major contributors to the extract’s potential. Binary mixtures between AOH and the two altertoxins respectively exhibited concentration-dependent antagonistic as well as synergistic combinatory effects. Notably, AME showed no efficacy towards EROD enzyme activity or impact on other toxins’ efficacy. Hence, this study provides insights into synergistic and other combinatory effects of Alternaria toxins in natural co-occurrence scenarios in the context of AhR signalling pathway activation in breast cancer cells.
Extraction of Carotenoids from Tomato Pomace via Water-Induced Hydrocolloidal Complexation
Authors: Nagarajan Jayesree , Pui Kay Hang , Krishnamurthy Nagendra Prasad , Ramakrishnan Nagasundara Ramanan , Aldawoud Turki M. S. , Galanakis Charis M. , Wei Ooi Chien
Published: July 2020

Agro-industrial waste is a largely untapped natural resource of bioactive compounds including carotenoids and pectin. However, conventional solvent extraction involves the excessive use of organic solvents, costly equipment, and tedious operation. These limitations of conventional extraction methods could be prospectively overcome by the carotenoid–pectin hydrocolloidal complexation. The complexation of lycopene and pectin was efficiently promoted in an aqueous environment, resulting in the colloidal complexes that can be subsequently recovered by sedimentation or centrifugation. In this study, the potential of carotenoid–pectin complexation on tomato pomace containing carotenoids and pectin was evaluated. Tomato pomace is a rich source of lycopene, β-carotene as well as pectin, making it suitable as the raw material for the carotenoid extraction. The extraction of carotenoid and pectin from tomato pomace was optimized using response surface methodology. The maximum recovery was 9.43 mg carotenoid fractions/100 g tomato pomace, while the purity of carotenoid-rich fractions was 92%. The antioxidant capacity of carotenoids extracted from the complexation method was found to be higher than that from the solvent extraction method. Moreover, extraction yield and antioxidant capacity of carotenoid obtained from the carotenoid–pectin complexation were comparable to that from solvent extraction. The carotenoid–pectin complexation is a promising green approach to valorize agro by-products for the extraction of valuable carotenoids.
Apoptosis-Inducing Factor, Mitochondrion-Associated 3 (AIFM3) Protein Level in the Sera as a Prognostic Marker of Cholangiocarcinoma Patients
Authors: Chua-on Daraporn , Proungvitaya Tanakorn , Tummanatsakun Doungdean , Techasen Anchalee , Limpaiboon Temduang , Roytrakul Sittiruk , Wongkham Sopit , Wongkham Chaisiri , Somintara Ongart , Sangkhamanon Sakkarn , Proungvitaya Siriporn
Published: July 2020

Prognosis of cholangiocarcinoma (CCA) patients is absolutely poor. Since improvement of prognosis and/or response to treatment by personalized and precision treatments requires earlier and precise diagnostic markers, discovery of prognostic markers attracts more attention. Apoptosis-inducing factor, mitochondrion-associated 3 (AIFM3) is highly expressed in several cancers including CCA. The present study investigated whether the serum AIFM3 level can be used as a potential marker for CCA prognosis. For this purpose, we first determined secretory protein nature of AIFM3 using bioinformatic tools. The results show that although AIFM3 lacks signal peptide, it can be secreted into plasma/serum via an unconventional pathway. Then, the AIFM3 levels in the sera of 141 CCA patients and 70 healthy controls (HC) were measured using a semi-quantitative dot blot assay. The results show that the AIFM3 level in the sera of CCA group was significantly higher than that of HC. When correlation between serum AIFM3 levels and the clinicopathological parameters of CCA patients were examined, serum AIFM3 levels correlated significantly with lymph node metastasis, age, and the patients’ overall survival (OS). Higher AIFM3 levels were significantly associated with shorter OS, and only AIFM3 was an independent prognostic marker for CCA. In conclusion, AIFM3 can be used as a prognostic marker for CCA.
The Hippo Pathway in Cardiac Regeneration and Homeostasis: New Perspectives for Cell-Free Therapy in the Injured Heart
Authors: Zheng Mingjie , Jacob Joan , Hung Shao-Hsi , Wang Jun
Published: July 2020

Intractable cardiovascular diseases are leading causes of mortality around the world. Adult mammalian hearts have poor regenerative capacity and are not capable of self-repair after injury. Recent studies of cell-free therapeutics such as those designed to stimulate endogenous cardiac regeneration have uncovered new feasible therapeutic avenues for cardiac repair. The Hippo pathway, a fundamental pathway with pivotal roles in cell proliferation, survival and differentiation, has tremendous potential for therapeutic manipulation in cardiac regeneration. In this review, we summarize the most recent studies that have revealed the function of the Hippo pathway in heart regeneration and homeostasis. In particular, we discuss the molecular mechanisms of how the Hippo pathway maintains cardiac homeostasis by directing cardiomyocyte chromatin remodeling and regulating the cell-cell communication between cardiomyocytes and non-cardiomyocytes in the heart.
Bi- and Tri-Specific T Cell Engager-Armed Oncolytic Viruses: Next-Generation Cancer Immunotherapy
Authors: Guo Zong Sheng , Lotze Michael T. , Zhu Zhi , Storkus Walter J. , Song Xiao-Tong
Published: July 2020

Oncolytic viruses (OVs) are potent anti-cancer biologics with a bright future, having substantial evidence of efficacy in patients with cancer. Bi- and tri-specific antibodies targeting tumor antigens and capable of activating T cell receptor signaling have also shown great promise in cancer immunotherapy. In a cutting-edge strategy, investigators have incorporated the two independent anti-cancer modalities, transforming them into bi- or tri-specific T cell engager (BiTE or TriTE)-armed OVs for targeted immunotherapy. Since 2014, multiple research teams have studied this combinatorial strategy, and it showed substantial efficacy in various tumor models. Here, we first provide a brief overview of the current status of oncolytic virotherapy and the use of multi-specific antibodies for cancer immunotherapy. We then summarize progress on BiTE and TriTE antibodies as a novel class of cancer therapeutics in preclinical and clinical studies, followed by a discussion of BiTE- or TriTE-armed OVs for cancer therapy in translational models. In addition, T cell receptor mimics (TCRm) have been developed into BiTEs and are expected to greatly expand the application of BiTEs and BiTE-armed OVs for the effective targeting of intracellular tumor antigens. Future applications of such innovative combination strategies are emerging as precision cancer immunotherapies.
Flammability Characteristics of Green Roofs
Authors: Gerzhova Nataliia , Blanchet Pierre , Dagenais Christian , Ménard Sylvain , Côté Jean
Published: July 2020

Assessing the fire risk of vegetated roofs includes the determination of their possible contribution to fire. Green roof components such as plants and growing media are organic materials and present a fuel that can catch and support the spread of fire. The flammability characteristics of these components were analyzed and compared to a typical roof covering. Growing media with 15% of organic matter were tested using cone calorimeter apparatus. The fuel load and heat release rate of the growing media were measured in both moist (30%) and dry conditions. It was observed that growing media in a moist condition do not present a fire risk, reaching a maximum heat release rate of 33 kW/m2. For dry substrates, a peak heat release rate of 95 kW/m2 was recorded in the first minute, which then rapidly decreased to 29 kW/m2 in the second minute. Compared to a typical bitumen roof membrane, the green roof showed a better fire performance. The literature data report more severe results for plant behavior, reaching peak heat release rates (HRRs) of 397 kW/m2 for dried and 176 kW/m2 for a green material. However, a rapid decrease in HRR to much lower values occurs in less than 2 min. The results also show that extensive and intensive types of green roofs present 22% and 95% of the additional fire load density when installed on a modified bitumen membrane, 19.7 and 85.8 MJ/m2, respectively.
Turbulent Flows and Pollution Dispersion around Tall Buildings Using Adaptive Large Eddy Simulation (LES)
Authors: Aristodemou Elsa , Mottet Letitia , Constantinou Achilleas , Pain Christopher
Published: July 2020

The motivation for this work stems from the increased number of high-rise buildings/skyscrapers all over the world, and in London, UK, and hence the necessity to see their effect on the local environment. We concentrate on the mean velocities, Reynolds stresses, turbulent kinetic energies (TKEs) and tracer concentrations. We look at their variations with height at two main locations within the building area, and downstream the buildings. The pollution source is placed at the top of the central building, representing an emission from a Combined Heat and Power (CHP) plant. We see how a tall building may have a positive effect at the lower levels, but a negative one at the higher levels in terms of pollution levels. Mean velocities at the higher levels (over 60 m in real life) are reduced at both locations (within the building area and downstream it), whilst Reynolds stresses and TKEs increase. However, despite the observed enhanced turbulence at the higher levels, mean concentrations increase, indicating that the mean flow has a greater influence on the dispersion. At the lower levels (Z < 60 m), the presence of a tall building enhanced dispersion (hence lower concentrations) for many of the configurations.
Improved Prognostic Prediction in Never-Smoker Lung Cancer Patients by Integration of a Systemic Inflammation Marker with Tumor Immune Contexture Analysis
Authors: Milione Massimo , Boeri Mattia , Cantarutti Anna , Centonze Giovanni , Busico Adele , Suatoni Paola , Garzone Giovanna , Cattaneo Laura , Tamborini Elena , Perrone Federica , Mangogna Alessandro , Corrao Giovanni , Pruneri Giancarlo , Sozzi Gabriella , Anichini Andrea , Pastorino Ugo
Published: July 2020

Almost 25% of lung cancers (LCs) occur in never-smokers. LC inflammatory profile, based on plasma C-reactive protein levels (CRP), predicts mortality, independently by smoking-status. We hypothesized that: CRP could be associated with tumor immune contexture (TIC) in never-smokers and both these two parameters may improve their prognosis. Sixty-eight never-smokers LC patients with high or low CRP were selected. The programmed cell death protein 1 (PD-1) and its ligand (PD-L1), the human leukocyte antigens (HLA-DR and HLA-I), CD8, CD4, CD3, CD33, CD163, and CD68 were evaluated by immunohistochemistry on surgical samples given TIC evaluation. The classification model based on TIC scores was generated by Classification and Regression Tree analysis. Tumor mutational burden was evaluated by targeted next-generation sequencing. Exclusively high CRP (H-CRP) subset showed PD-L1 expression in 35% of LC as well as lower HLA-I and HLA-DR in their stromal cells. CD3, CD4, CD8, HLA-I, HLA-DR tumor cells staining were associated with a “low inflammatory profile” subset. CRP and LC immune profiles drive clinical outcome: 5-year survival 88% against 8% was associated with low and high-risk profiles (p < 0.0001). Clinical outcome prediction in never-smoker LC patients may be improved by both CRP and tumor immune contexture evaluation.
The Role of Liquid Biopsies in Detecting Molecular Tumor Biomarkers in Brain Cancer Patients
Authors: Sareen Heena , Garrett Celine , Lynch David , Powter Branka , Brungs Daniel , Cooper Adam , Po Joseph , Koh Eng-Siew , Vessey Joey Yusof , McKechnie Simon , Bazina Renata , Sheridan Mark , Gelder James van , Darwish Balsam , Jaeger Mathias , Roberts Tara L. , De Souza Paul , Becker Therese M.
Published: July 2020

Glioblastoma multiforme (GBM) is one of the most lethal primary central nervous system cancers with a median overall survival of only 12–15 months. The best documented treatment is surgical tumor debulking followed by chemoradiation and adjuvant chemotherapy with temozolomide, but treatment resistance and therefore tumor recurrence, is the usual outcome. Although advances in molecular subtyping suggests GBM can be classified into four subtypes, one concern about using the original histology for subsequent treatment decisions is that it only provides a static snapshot of heterogeneous tumors that may undergo longitudinal changes over time, especially under selective pressure of ongoing therapy. Liquid biopsies obtained from bodily fluids like blood and cerebro-spinal fluid (CSF) are less invasive, and more easily repeated than surgery. However, their deployment for patients with brain cancer is only emerging, and possibly suppressed clinically due to the ongoing belief that the blood brain barrier prevents the egress of circulating tumor cells, exosomes, and circulating tumor nucleic acids into the bloodstream. Although brain cancer liquid biopsy analyses appear indeed challenging, advances have been made and here we evaluate the current literature on the use of liquid biopsies for detection of clinically relevant biomarkers in GBM to aid diagnosis and prognostication.
Environmental Assessment of Humic Acid Coated Magnetic Materials Used as Catalyst in Photo-Fenton Processes
Authors: Costamagna Mattia , Gonçalves Nuno P. F. , Bianco Prevot Alessandra
Published: July 2020

Persistent organic pollutants have been increasingly detected in natural waters, and this represents a real challenge to the quality of this resource. To remove these species, advanced treatment technologies are required. Among these technologies, Fenton-like and photo-Fenton-like processes have been investigated for the removal of pollutants from water. Delicate aspects of photo-Fenton processes are that light-driven processes are energy intensive and require a fair amount of chemical inputs, which strongly affects their overall environmental burdens. At present, aside from determining the efficiency of the processes to remove pollutants of a particular technology, it becomes fundamental to assess also the environmental sustainability of the overall process. In this work, the methodology of the life cycle assessment (LCA) was applied to identify the hotspots of using magnetite particles covered with humic acid (Fe3O4/HA) as a heterogeneous photo-Fenton catalyst for water remediation. The sustainability of the overall process was considered, and a comparative LCA study was performed between H2O2 and persulfate activation at different pH. The addition of humic substances to the particles allows the effectiveness of the catalyst to improve without increasing the environmental impacts; these processes are strongly correlated with energy consumption and therefore with the efficiency of the process. For this reason, working at acidic pH allows us to contain the impacts.
The Anti-Cancer Drug Dabrafenib Is a Potent Activator of the Human Pregnane X Receptor
Authors: Creusot Nicolas , Gassiot Matthieu , Alaterre Elina , Chiavarina Barbara , Grimaldi Marina , Boulahtouf Abdelhay , Toporova Lucia , Gerbal-Chaloin Sabine , Daujat-Chavanieu Martine , Matheux Alice , Rahmani Roger , Gongora Céline , Evrard Alexandre , Pourquier Philippe , Balaguer Patrick
Published: July 2020

The human pregnane X receptor (hPXR) is activated by a large set of endogenous and exogenous compounds and plays a critical role in the control of detoxifying enzymes and transporters regulating liver and gastrointestinal drug metabolism and clearance. hPXR is also involved in both the development of multidrug resistance and enhanced cancer cells aggressiveness. Moreover, its unintentional activation by pharmaceutical drugs can mediate drug–drug interactions and cause severe adverse events. In that context, the potential of the anticancer BRAF inhibitor dabrafenib suspected to activate hPXR and the human constitutive androstane receptor (hCAR) has not been thoroughly investigated yet. Using different reporter cellular assays, we demonstrate that dabrafenib can activate hPXR as efficiently as its reference agonist SR12813, whereas it does not activate mouse or zebrafish PXR nor hCAR. We also showed that dabrafenib binds to recombinant hPXR, induces the expression of hPXR responsive genes in colon LS174T-hPXR cancer cells and human hepatocytes and finally increases the proliferation in LS174T-hPXR cells. Our study reveals that by using a panel of different cellular techniques it is possible to improve the assessment of hPXR agonist activity for new developed drugs.
The NLRP3 Inflammasome Role in the Pathogenesis of Pregnancy Induced Hypertension and Preeclampsia
Authors: Socha Maciej W. , Malinowski Bartosz , Puk Oskar , Dubiel Mariusz , Wiciński Michał
Published: July 2020

Pregnancy-induced hypertension and preeclampsia are associated with significant maternal and fetal mortality. A better understanding of these diseases, delineation of molecular pathomechanism, and efficient treatment development are some of the most urgent tasks in obstetrics and gynecology. Recent findings indicate the crucial role of inflammation in the development of hypertension and preeclampsia. Although the mechanism is very complex and needs further explanation, it appears that high levels of cholesterol, urate, and glucose activates NLRP3 inflammasome, which produces IL-1β, IL-18, and gasdermin D. Production of these proinflammatory chemokines is the beginning of a local and general inflammation, which results in sympathetic outflow, angiotensin II production, proteinuria, hemolysis, liver damage, immunothrombosis, and coagulopathy. The NLRP3 inflammasome is a critical complex in the mediation of the inflammatory response, which makes it crucial for the development of pregnancy-induced hypertension and preeclampsia, as well as its complications, such as placental abruption and HELLP (hemolysis, elevated liver enzymes, and low platelets) syndrome. Herein, the presented article delineates molecular mechanisms of these processes, indicating directions of future advance.
A Novel Small-Molecule Inhibitor of Endosomal TLRs Reduces Inflammation and Alleviates Autoimmune Disease Symptoms in Murine Models
Authors: Patra Mahesh Chandra , Achek Asma , Kim Gi-Young , Panneerselvam Suresh , Shin Hyeon-Jun , Baek Wook-Yong , Lee Wang Hee , Sung June , Jeong Uisuk , Cho Eun-Young , Kim Wook , Kim Eunha , Suh Chang-Hee , Choi Sangdun
Published: July 2020

Toll-like receptors (TLRs) play a fundamental role in the inflammatory response against invading pathogens. However, the dysregulation of TLR-signaling pathways is implicated in several autoimmune/inflammatory diseases. Here, we show that a novel small molecule TLR-inhibitor (TAC5) and its derivatives TAC5-a, TAC5-c, TAC5-d, and TAC5-e predominantly antagonized poly(I:C) (TLR3)-, imiquimod (TLR7)-, TL8-506 (TLR8)-, and CpG-oligodeoxynucleotide (TLR9)-induced signaling pathways. TAC5 and TAC5-a significantly hindered the activation of nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB), reduced the phosphorylation of mitogen-activated protein kinases, and inhibited the secretion of tumor necrosis factor-α (TNF-α) and interleukin-6. Besides, TAC5-a prevented the progression of psoriasis and systemic lupus erythematosus (SLE) in mice. Interestingly, TAC5 and TAC5-a did not affect Pam3CSK4 (TLR1/2)-, FSL-1 (TLR2/6)-, or lipopolysaccharide (TLR4)-induced TNF-α secretion, indicating their specificity towards endosomal TLRs (TLR3/7/8/9). Collectively, our data suggest that the TAC5 series of compounds are potential candidates for treating autoimmune diseases such as psoriasis or SLE.
Radiation Response of Murine Embryonic Stem Cells
Authors: Hellweg Christine E. , Shinde Vaibhav , Srinivasan Sureshkumar Perumal , Henry Margit , Rotshteyn Tamara , Baumstark-Khan Christa , Schmitz Claudia , Feles Sebastian , Spitta Luis F. , Hemmersbach Ruth , Hescheler Jürgen , Sachinidis Agapios
Published: July 2020

To understand the mechanisms of disturbed differentiation and development by radiation, murine CGR8 embryonic stem cells (mESCs) were exposed to ionizing radiation and differentiated by forming embryoid bodies (EBs). The colony forming ability test was applied for survival and the MTT test for viability determination after X-irradiation. Cell cycle progression was determined by flow cytometry of propidium iodide-stained cells, and DNA double strand break (DSB) induction and repair by γH2AX immunofluorescence. The radiosensitivity of mESCs was slightly higher compared to the murine osteoblast cell line OCT-1. The viability 72 h after X-irradiation decreased dose-dependently and was higher in the presence of leukemia inhibitory factor (LIF). Cells exposed to 2 or 7 Gy underwent a transient G2 arrest. X-irradiation induced γH2AX foci and they disappeared within 72 h. After 72 h of X-ray exposure, RNA was isolated and analyzed using genome-wide microarrays. The gene expression analysis revealed amongst others a regulation of developmental genes (Ada, Baz1a, Calcoco2, Htra1, Nefh, S100a6 and Rassf6), downregulation of genes involved in glycolysis and pyruvate metabolism whereas upregulation of genes related to the p53 signaling pathway. X-irradiated mESCs formed EBs and differentiated toward cardiomyocytes but their beating frequencies were lower compared to EBs from unirradiated cells. These results suggest that X-irradiation of mESCs deregulate genes related to the developmental process. The most significant biological processes found to be altered by X-irradiation in mESCs were the development of cardiovascular, nervous, circulatory and renal system. These results may explain the X-irradiation induced-embryonic lethality and malformations observed in animal studies.
DNA Damage: From Threat to Treatment
Authors: Carusillo Antonio , Mussolino Claudio
Published: July 2020

DNA is the source of genetic information, and preserving its integrity is essential in order to sustain life. The genome is continuously threatened by different types of DNA lesions, such as abasic sites, mismatches, interstrand crosslinks, or single-stranded and double-stranded breaks. As a consequence, cells have evolved specialized DNA damage response (DDR) mechanisms to sustain genome integrity. By orchestrating multilayer signaling cascades specific for the type of lesion that occurred, the DDR ensures that genetic information is preserved overtime. In the last decades, DNA repair mechanisms have been thoroughly investigated to untangle these complex networks of pathways and processes. As a result, key factors have been identified that control and coordinate DDR circuits in time and space. In the first part of this review, we describe the critical processes encompassing DNA damage sensing and resolution. In the second part, we illustrate the consequences of partial or complete failure of the DNA repair machinery. Lastly, we will report examples in which this knowledge has been instrumental to develop novel therapies based on genome editing technologies, such as CRISPR-Cas.
RETRACTED: Leong et al. Artificial Intelligence Algorithm Enabled Industrial-Scale Graphene Characterization. Crystals 2020, 10, 308
Authors:   Crystals Editorial Office
Published: July 2020

The Crystals Editorial Office has been made aware that the data and results in this published paper [...]
Unlimited Power Division Ratio of Microstrip Balanced-to-Unbalanced Gysel-Type Arbitrary Power Divider
Authors: Zhu Zihui , Wang Zhongbao , Fu Ye , Fang Shaojun , Liu Hongmei , Chen Zhi Ning
Published: July 2020

A microstrip balanced-to-unbalanced (BTU) Gysel-type arbitrary power divider without the high-impedance transmission-line (TL) section is proposed to eliminate the power division ratio (PDR) limit of the conventional microstrip BTU power dividers. The proposed circuit includes five moderate-impedance TLs having the same characteristic impedance in addition to a grounded resistor. The arbitrary PDR is easily obtained by varying the electrical length of the TLs without changing the characteristic impedances, especially the large PDR, which is difficult to achieve by means of conventional BTU power dividers. When the PDR is ∞, the proposed circuit becomes a balun. The closed-form design equations are derived and discussed. To verify the proposed circuit, three prototypes I, II, and III are designed and fabricated for PDRs of 10 dB, 20 dB, and ∞ dB, respectively. The measured PDRs are in good agreement with the simulations. The measured isolation between the output ports is higher than 31 dB for prototypes I and II. The measured insertion loss of the balun prototype is 0.194 dB. Furthermore, the common-mode suppression of greater than 32 dB and the return loss of higher than 22 dB are obtained for various PDRs.
Cost and Energy Reduction of a New nZEB Wooden Building
Authors: Arumägi Endrik , Kalamees Targo
Published: July 2020

The current study demonstrates the possibilities of reducing energy use and construction costs and provides evidence that wooden nearly-zero-energy buildings (nZEB) are technically possible at affordable construction costs by using novel design processes and procurement models that enable scalable and modular production. The energy efficiency solutions were derived by increasing/decreasing the insulation value of the building envelope in successive steps. Financial calculations were based on the investment needed to achieve the nearly-zero-energy levels. Overall, many opportunities exist to decrease the cost and energy use compared to the current (pre-nZEB) practice because the net present value can change up to 150 €/m² on the same energy performance indicator (EPI) level. The EPI in the cost-even range was reached by combining a ground-source heat pump (between 115 and 128 kWh/(m2·a)) and efficient district heating (between 106 and 124 kWh/(m2·a)). As energy efficiency decreases, improving energy efficiency becomes more expensive by insulation measures. Throughout the EPI range the most cost efficient was investment in the improvement of the thermal transmittance of windows (3–13 €/(kWh/(m2·a))) while investments in other building envelope parts were less effective (4–80 €/(kWh/(m2·a))). If these were possible to install, photovoltaic (PV) panels installed to the roof would be the cheapest solution to improve the energy performance. Integrated project delivery procurement (design and construction together) and the use of prefabricated wooden structures reduced the constructing cost by half (from ~2700 €/net m2 to 1390 €/net m2) and helped to keep the budget within limits.
Detecting Vegetation Recovery after Fire in A Fire-Frequented Habitat Using Normalized Difference Vegetation Index (NDVI)
Authors: Lacouture Danielle L. , Broadbent Eben N. , Crandall Raelene M.
Published: July 2020

Research Highlights: Fire-frequented savannas are dominated by plant species that regrow quickly following fires that mainly burn through the understory. To detect post-fire vegetation recovery in these ecosystems, particularly during warm, rainy seasons, data are needed on a small, temporal scale. In the past, the measurement of vegetation regrowth in fire-frequented systems has been labor-intensive, but with the availability of daily satellite imagery, it should be possible to easily determine vegetation recovery on a small timescale using Normalized Difference Vegetation Index (NDVI) in ecosystems with a sparse overstory. Background and Objectives: We explore whether it is possible to use NDVI calculated from satellite imagery to detect time-to-vegetation recovery. Additionally, we determine the time-to-vegetation recovery after fires in different seasons. This represents one of very few studies that have used satellite imagery to examine vegetation recovery after fire in southeastern U.S.A. pine savannas. We test the efficacy of using this method by examining whether there are detectable differences between time-to-vegetation recovery in subtropical savannas burned during different seasons. Materials and Methods: NDVI was calculated from satellite imagery approximately monthly over two years in a subtropical savanna with units burned during dry, dormant and wet, growing seasons. Results: Despite the availability of daily satellite images, we were unable to precisely determine when vegetation recovered, because clouds frequently obscured our range of interest. We found that, in general, vegetation recovered in less time after fire during the wet, growing, as compared to dry, dormant, season, albeit there were some discrepancies in our results. Although these general patterns were clear, variation in fire heterogeneity and canopy type and cover skewed NDVI in some units. Conclusions: Although there are some challenges to using satellite-derived NDVI, the availability of satellite imagery continues to improve on both temporal and spatial scales, which should allow us to continue finding new and efficient ways to monitor and model forests in the future.
Evaluating the Ability of FARSITE to Simulate Wildfires Influenced by Extreme, Downslope Winds in Santa Barbara, California
Authors: Zigner Katelyn , Carvalho Leila M. V. , Peterson Seth , Fujioka Francis , Duine Gert-Jan , Jones Charles , Roberts Dar , Moritz Max
Published: July 2020

Extreme, downslope mountain winds often generate dangerous wildfire conditions. We used the wildfire spread model Fire Area Simulator (FARSITE) to simulate two wildfires influenced by strong wind events in Santa Barbara, CA. High spatial-resolution imagery for fuel maps and hourly wind downscaled to 100 m were used as model inputs, and sensitivity tests were performed to evaluate the effects of ignition timing and location on fire spread. Additionally, burn area rasters from FARSITE simulations were compared to minimum travel time rasters from FlamMap simulations, a wildfire model similar to FARSITE that holds environmental variables constant. Utilization of two case studies during strong winds revealed that FARSITE was able to successfully reconstruct the spread rate and size of wildfires when spotting was minimal. However, in situations when spotting was an important factor in rapid downslope wildfire spread, both FARSITE and FlamMap were unable to simulate realistic fire perimeters. We show that this is due to inherent limitations in the models themselves, related to the slope-orientation relative to the simulated fire spread, and the dependence of ember launch and land locations. This finding has widespread implications, given the role of spotting in fire progression during extreme wind events.