bluuebunny/crossref_metadata_2025 huggingface dataset:
Assessing Prognostic and Predictive Biomarkers of Regorafenib Response in Patients with Advanced Soft Tissue Sarcoma: REGOSARC Study
Authors: Brodowicz Thomas , Liegl-Atzwanger Bernadette , Penel Nicolas , Mir Olivier , Blay Jean-Yves , Kashofer Karl , Le Cesne Axel , Decoupigny Emilie , Wallet Jennifer , Hamacher Rainer , Le Deley Marie-Cecile
Published: December 2020

Regorafenib significantly prolonged progression-free survival (PFS) in pretreated patients with advanced non-adipocytic sarcoma (HR = 0.46; p < 0.001) in a placebo-controlled, randomized, phase-II trial (NCT01900743). Thus, here, we assessed the prevalence of 57 biomarkers and their prognostic and predictive values for PFS and overall survival (OS). We analyzed 134/182 patients included in this trial, treated with regorafenib (n = 71, 53%) or placebo (n = 63, 47%). Mutational analyses were performed via full coding sequence analysis for 10 genes, and mutation hotspot panel for 50 genes (four genes in common). H19 was studied with RNA in-situ hybridization. The prognostic and predictive biomarkers’ values were studied only for biomarkers found positive/mutated in at least 10 patients. Overall, 25 out of 57 studied biomarkers, including five out of seven genes involved in angiogenesis, were found mutated/positive in at least one patient, of which 23 biomarkers had low prevalence (fewer than eight out of 134 patients), contrasting with H19 (n = 24, 18%), and TP53 (n = 35, 26%). However, in multivariable models of PFS and OS, including treatment effects and interactions, no significant prognostic or predictive values of the tested biomarkers were observed. Though several promising biomarkers were found to be positive/mutated, none of them were identified as viable predictive and prognostic biomarkers.
Increased Immunogenicity of a Minimally Immunogenic Tumor after Cancer-Targeting Near Infrared Photoimmunotherapy
Authors: Wakiyama Hiroaki , Furusawa Aki , Okada Ryuhei , Inagaki Fuyuki , Kato Takuya , Maruoka Yasuhiro , Choyke Peter L. , Kobayashi Hisataka
Published: December 2020

Near-infrared photoimmunotherapy (NIR-PIT) is a highly selective cancer treatment that employs an antibody photoabsorber conjugate (APC) composed of a targeting monoclonal antibody (mAb) conjugated with a photoactivatable phthalocyanine-derivative dye. Once injected and allowed to bind to a tumor, the APC is activated by local near-infrared light which kills cancer cells and induces a strong immune response in the tumor microenvironment by unmasking of new tumor antigens emerging from damaged tumor cells. Due to its ability to incite an immune reaction, even in poorly immunogenic tumors, NIR-PIT has the potential to enhance immunogenicity in tumors especially after immune checkpoint inhibition. In this study, we employ a poorly immunogenic MOC2-luc syngeneic tumor model and evaluate the efficacy of cancer-targeting CD44-targeted NIR-PIT. Increased infiltration of CD8+ T cells observed after NIR-PIT suggested an enhanced immune environment. Next, we evaluated tumor progression and survival after the combination of CD44-targeted NIR-PIT and short-term administration of an anti-PD1 immune checkpoint inhibitor (ICI) to further activate CD8+ T cells. Additionally, in mice in which the tumors were eradicated by this combination therapy, a re-challenge with fresh MOC2-luc cells demonstrated failure of tumor implantation implying acquired long-term immunity against the cancer cells. Combination therapy decreased tumor progression and prolonged survival significantly. Therefore, we concluded that NIR-PIT was able to convert a minimally immunogenic tumor unresponsive to anti-PD-1 ICI into a highly immunogenic tumor responsive to anti-PD-1 ICI, and this therapy was capable of inducing long-term immunity against the treated cancer.
Individualizing Systemic Therapies in First Line Treatment and beyond for Advanced Renal Cell Carcinoma
Authors: Khan Yasir , Slattery Timothy D. , Pickering Lisa M.
Published: December 2020

Therapeutic options for treating advanced renal cell cancer (RCC) are rapidly evolving. Vascular endothelial growth factor (VEGF)-directed therapy, predominantly VEGF receptor (VEGFr) tyrosine kinase inhibitors (TKIs) had been the most effective first line treatment since 2005 irrespective of International Metastatic RCC Database Consortium (IMDC) risk stratification. However, immune checkpoint inhibitors (ICI) have recently changed the treatment paradigm for advanced RCC particularly as the first-line systemic treatment modality. The combination of Ipilimumab and Nivolumab provides better disease control and long-term outcomes compared with the anti-VEGFr TKI Sunitinib for IMDC intermediate- to poor-risk patients and we now have the option of using ICI with TKI upfront for all IMDC risk groups. This poses a challenge for physicians, both to select the most suitable first line regimen and the most suitable subsequent therapy given the lack of data about sequencing in this setting. This treatment landscape is expected to become more complex with the emerging treatment options. Moreover, these therapeutic options cannot be generalized as significant variability exists between individual’s disease biologies and their physiologies for handling treatment adverse effects. Notable efforts are being made to identify promising predictive biomarkers ranging from neo-antigen load to gene expression profiling. These biomarkers need prospective validation to justify their utility in clinical practice and in treatment decision making. This review article discusses various clinicopathological characteristics that should be carefully evaluated to help select appropriate treatment and discusses the current status of biomarker-based selection.
The Art of Mast Cell Adhesion
Authors: Pastwińska Joanna , Żelechowska Paulina , Walczak-Drzewiecka Aurelia , Brzezińska-Błaszczyk Ewa , Dastych Jarosław
Published: December 2020

Cell adhesion is one of the basic phenomena occurring in a living organism, affecting many other processes such as proliferation, differentiation, migration, or cell viability. Mast cells (MCs) are important elements involved in defending the host against various pathogens and regulating inflammatory processes. Due to numerous mediators, they are contributing to the modulation of many basic cellular processes in a variety of cells, including the expression and functioning of different adhesive molecules. They also express themselves many adhesive proteins, including ICAM-1, ICAM-3, VCAM-1, integrins, L-selectin, E-cadherin, and N-cadherin. These molecules enable MCs to interact with other cells and components of the extracellular matrix (ECM), creating structures such as adherens junctions and focal adhesion sites, and triggering a signaling cascade. A thorough understanding of these cellular mechanisms can create a better understanding of MC biology and reveal new goals for MC targeted therapy. This review will focus on the current knowledge of adhesion mechanisms with the involvement of MCs. It also provides insight into the influence of MCs or MC-derived mediators on the adhesion molecule expression in different cells.
Profiling and Targeting of Energy and Redox Metabolism in Grade 2 Bladder Cancer Cells with Different Invasiveness Properties
Authors: Pasquale Valentina , Ducci Giacomo , Campioni Gloria , Ventrici Adria , Assalini Chiara , Busti Stefano , Vanoni Marco , Vago Riccardo , Sacco Elena
Published: December 2020

Bladder cancer is one of the most prevalent deadly diseases worldwide. Grade 2 tumors represent a good window of therapeutic intervention, whose optimization requires high resolution biomarker identification. Here we characterize energy metabolism and cellular properties associated with spreading and tumor progression of RT112 and 5637, two Grade 2 cancer cell lines derived from human bladder, representative of luminal-like and basal-like tumors, respectively. The two cell lines have similar proliferation rates, but only 5637 cells show efficient lateral migration. In contrast, RT112 cells are more prone to form spheroids. RT112 cells produce more ATP by glycolysis and OXPHOS, present overall higher metabolic plasticity and are less sensitive than 5637 to nutritional perturbation of cell proliferation and migration induced by treatment with 2-deoxyglucose and metformin. On the contrary, spheroid formation is less sensitive to metabolic perturbations in 5637 than RT112 cells. The ability of metformin to reduce, although with different efficiency, cell proliferation, sphere formation and migration in both cell lines, suggests that OXPHOS targeting could be an effective strategy to reduce the invasiveness of Grade 2 bladder cancer cells.
The mRNA Distribution of Cancer Stem Cell Marker CD90/Thy-1 Is Comparable in Hepatocellular Carcinoma of Eastern and Western Populations
Authors: Luong An B. , Do Huy Q. , Tarchi Paola , Bonazza Deborah , Bottin Cristina , Cabral Loraine Kay D. , Tran Long D. C. , Doan Thao P. T. , Crocè Lory S. , Pham Hoa L. T. , Tiribelli Claudio , Sukowati Caecilia H. C.
Published: December 2020

Epidemiology of hepatocellular carcinoma (HCC) showed a correlation between incidence and geographical-relevant risk factors. This study aims to compare the distributions of cancer stem cells (CSC) in two distant populations in Asia and Europe. We analyzed 52 and 43 selected HCC patients undergoing hepatectomy in Ho Chi Minh City (Vietnam) and Trieste (Italy). Each patient sample consisted of HCC, peri-HCC, and non-tumoral (distal) tissue. Demographic data were recorded together with clinical findings. The protocol for the collection of tissue samples and RNA was standardized in both laboratories and gene expression analysis was performed in a single laboratory with identical PCR conditions. Baseline data showed comparable laboratory findings between the two cohorts. mRNA distribution showed a comparable pattern of all CSC markers analyzed with the expression of CD90 progressively increasing from distal and peri-HCC to be highest in HCC (p < 0.001), confirmed by immunofluorescence data. CD90 mRNA distribution was related to HBV-related HCC and a tumor diameter less than 5 cm. Patients with high tumoral CD90 mRNA had a shorter time (p < 0.05) to tumor recurrence compared to patients with lower CD90. This comparative study showed that CD90 mRNA expressions are comparable between Eastern and Western HCC cases.
IgA2 Antibodies against SARS-CoV-2 Correlate with NET Formation and Fatal Outcome in Severely Diseased COVID-19 Patients
Authors: Staats Léonie A. N. , Pfeiffer Hella , Knopf Jasmin , Lindemann Aylin , Fürst Julia , Kremer Andreas E. , Hackstein Holger , Neurath Markus F. , Muñoz Luis E. , Achenbach Susanne , Leppkes Moritz , Herrmann Martin , Schett Georg , Steffen Ulrike
Published: December 2020

Infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) leads to an adaptive immune response in the host and the formation of anti-SARS-CoV-2 specific antibodies. While IgG responses against SARS-CoV-2 have been characterized quite well, less is known about IgA. IgA2 activates immune cells and induces inflammation and neutrophil extracellular trap (NET) formation which may contribute to organ injury and fatal outcome in SARS-CoV-2-infected patients. SARS-CoV-2 spike protein specific antibody levels were measured in plasma samples of 15 noninfected controls and 82 SARS-CoV-2-infected patients with no or mild symptoms, moderate symptoms (hospitalization) or severe disease (intensive care unit, ICU). Antibody levels were compared to levels of C-reactive protein (CRP) and circulating extracellular DNA (ecDNA) as markers for general inflammation and NET formation, respectively. While levels of SARS-CoV-2-specific IgG were similar in all patient groups, IgA2 antibodies were restricted to severe disease and showed the strongest discrimination between nonfatal and fatal outcome in patients with severe SARS-CoV-2 infection. While anti-SARS-CoV-2 IgG and IgA2 levels correlated with CRP levels in severely diseased patients, only anti-SARS-CoV-2 IgA2 correlated with ecDNA. These data suggest that the formation of anti-SARS-CoV-2 IgA2 during SARS-CoV-2 infection is a marker for more severe disease related to NET formation and poor outcome.
NOTCH1 Signaling in Head and Neck Squamous Cell Carcinoma
Authors: Shah Pooja A. , Huang Chenfei , Li Qiuli , Kazi Sawad A. , Byers Lauren A. , Wang Jing , Johnson Faye M. , Frederick Mitchell J.
Published: December 2020

Biomarker-driven targeted therapies are lacking for head and neck squamous cell carcinoma (HNSCC), which is common and lethal. Efforts to develop such therapies are hindered by a genomic landscape dominated by the loss of tumor suppressor function, including NOTCH1 that is frequently mutated in HNSCC. Clearer understanding of NOTCH1 signaling in HNSCCs is crucial to clinically targeting this pathway. Structural characterization of NOTCH1 mutations in HNSCC demonstrates that most are predicted to cause loss of function, in agreement with NOTCH1’s role as a tumor suppressor in this cancer. Experimental manipulation of NOTCH1 signaling in HNSCC cell lines harboring either mutant or wild-type NOTCH1 further supports a tumor suppressor function. Additionally, the loss of NOTCH1 signaling can drive HNSCC tumorigenesis and clinical aggressiveness. Our recent data suggest that NOTCH1 controls genes involved in early differentiation that could have different phenotypic consequences depending on the cancer’s genetic background, including acquisition of pseudo-stem cell-like properties. The presence of NOTCH1 mutations may predict response to treatment with an immune checkpoint or phosphatidylinositol 3-kinase inhibitors. The latter is being tested in a clinical trial, and if validated, it may lead to the development of the first biomarker-driven targeted therapy for HNSCC.
Human Astrocytes Model Derived from Induced Pluripotent Stem Cells
Authors: Leventoux Nicolas , Morimoto Satoru , Imaizumi Kent , Sato Yuta , Takahashi Shinichi , Mashima Kyoko , Ishikawa Mitsuru , Sonn Iki , Kondo Takahiro , Watanabe Hirotaka , Okano Hideyuki
Published: December 2020

Induced pluripotent stem cell (iPSC)-based disease modeling has a great potential for uncovering the mechanisms of pathogenesis, especially in the case of neurodegenerative diseases where disease-susceptible cells can usually not be obtained from patients. So far, the iPSC-based modeling of neurodegenerative diseases has mainly focused on neurons because the protocols for generating astrocytes from iPSCs have not been fully established. The growing evidence of astrocytes’ contribution to neurodegenerative diseases has underscored the lack of iPSC-derived astrocyte models. In the present study, we established a protocol to efficiently generate iPSC-derived astrocytes (iPasts), which were further characterized by RNA and protein expression profiles as well as functional assays. iPasts exhibited calcium dynamics and glutamate uptake activity comparable to human primary astrocytes. Moreover, when co-cultured with neurons, iPasts enhanced neuronal synaptic maturation. Our protocol can be used for modeling astrocyte-related disease phenotypes in vitro and further exploring the contribution of astrocytes to neurodegenerative diseases.
Synthesis of Single-Phase Zeolite A by Coal Gasification Fine Slag from Ningdong and Its Application as a High-Efficiency Adsorbent for Cu2+ and Pb2+ in Simulated Waste Water
Authors: Ji Wenxin , Feng Ning , Zhao Pengde , Zhang Shiyue , Zhang Shasha , Lan Liping , Huang Honglan , Li Kangning , Sun Yonggang , Li Yuanyuan , Ma Yulong
Published: December 2020

Coal gasification is a new direction for the clean utilization of coal, but it also brings huge environmental pressure on solid waste. In this paper, the high-crystallinity single-phase zeolite A was prepared by solid-phase alkali fusion synthesis from coal gasification fine slag (CGFS), without template agent, with low water consumption, and with low cost, and it was used to remove heavy metals such as Pb2+ and Cu2+ in simulated waste water. The main factors affecting the solid-phase and green synthesis methods were analyzed, and the optimum conditions for solid-phase synthesis of high-crystallinity single-phase zeolite A were determined as follows: NaOH/CGFS = 1.2; solid-phase alkali fusion temperature 823 K, solid-phase alkali fusion 90 min, liquid–solid ratio 4.5, and 353 K hydrothermal reaction for 12 h. The relative crystallinity, specific surface area, and ion-exchange capacity of single-phase zeolites A are 93.1%, 61.09 m2/g, and 268.4 mmol/100 g. The removal rates of Pb2+ and Cu2+ can reach more than 99%, especially for the removal efficiency of Pb2+, which is common in simulated waste water. This is an effective method with important application prospects, and it formed an effective way to recycle solid waste of coal chemical industry.
Fabrication of a 3D-Printed Porous Junction for Ag|AgCl|gel-KCl Reference Electrode
Authors: Sibug-Torres Sarah May , Go Lance P. , Enriquez Erwin P.
Published: December 2020

Fused filament fabrication (FFF) is a 3D printing method that is attracting increased interest in the development of miniaturized electrochemical sensor systems due to its versatility, low cost, reproducibility, and capability for rapid prototyping. A key component of miniaturized electrochemical systems is the reference electrode (RE). However, reports of the fabrication of a true 3D-printed RE that exhibits stability to variations in the sample matrix remain limited. In this work, we report the development and characterization of a 3D-printed Ag|AgCl|gel-KCl reference electrode (3D-RE). The RE was constructed using a Ag|AgCl wire and agar-KCl layer housed in a watertight 3D-printed acrylonitrile butadiene styrene (ABS) casing. The novel feature of our electrode is a 3D-printed porous junction that protects the gel electrolyte layer from chloride ion leakage and test sample contamination while maintaining electrical contact with the sample solution. By tuning the 3D printing filament extrusion ratio (k), the porosity of the junction was adjusted to balance the reference electrode potential stability and impedance. The resulting 3D-RE demonstrated a stable potential, with a potential drift of 4.55 ± 0.46 mV over a 12-h period of continuous immersion in 0.1 M KCl, and a low impedance of 0.50 ± 0.11 kΩ. The 3D-RE was also insensitive to variations in the sample matrix and maintained a stable potential for at least 30 days under proper storage in 3 M KCl. We demonstrate the application of this 3D-RE in cyclic voltammetry and in pH sensing coupled with electrodeposited iridium oxide on a gold electrode. Our method offers a viable strategy for 3D printing a customizable true reference electrode that can be readily fabricated on demand and integrated into 3D-printed miniaturized electrochemical sensor systems.
Functional Disability in Adolescents with Chronic Pain: Comparing an Interdisciplinary Exposure Program to Usual Care
Authors: Dekker Carolien , Goossens Mariëlle , Winkens Bjorn , Remerie Silvia , Bastiaenen Caroline , Verbunt Jeanine
Published: December 2020

(1) Background: Chronic musculoskeletal pain (CMP) in adolescents can negatively affect physical, psychological, and social functioning, resulting in functional disability. This randomized controlled trial (RCT) aimed to evaluate the effectiveness of an outpatient rehabilitation program based on graded exposure in vivo (EP) compared with care as usual (CAU: interdisciplinary outpatient rehabilitation care). Both EP and CAU aim to improve functional ability in adolescents with CMP. (2) Methods: Pragmatic multicenter RCT with 12-month follow-up. Adolescents (12–21 years) with CMP were invited to participate. Primary outcome: functional disability; secondary outcomes: perceived harmfulness; pain catastrophizing; pain intensity. Data analysis: intention-to-treat linear mixed model. (3) Results: Sixty adolescents (mean 16 years) were randomized; data for 53 were analyzed. Adolescents in EP showed relevant and significant decreases in functional disability (estimated mean difference at least −8.81, p ≤ 0.01) compared with CAU at all times. Significant differences in favor of EP were found for perceived harmfulness at all times (p ≤ 0.002), for pain catastrophizing at 2 months (p = 0.039) and for pain intensity at 4 and 10 months (p ≤ 0.028). (4) Conclusion: EP leads to a significant and clinically relevant decrease in functional disability compared with usual care.
Controlled Deposition of Lead Iodide and Lead Chloride Thin Films by Low-Pressure Chemical Vapor Deposition
Authors: Ngqoloda Siphelo , Arendse Christopher J. , Muller Theophillus F. , Magubane Siphesihle S. , Oliphant Clive J.
Published: December 2020

Lead halide thin films, such as lead iodide (PbI2) and lead chloride (PbCl2), are used as precursor films for perovskite preparation, which is frequently achieved by vacuum thermal evaporation but rarely by the low-pressure chemical vapor deposition (CVD) method. Here, we report on the deposition of PbI2 and PbCl2 thin films on glass substrates by employing the low-pressure CVD method. The effect of the substrate temperature on the structure and morphology of the lead halide films is investigated. Crystalline films were realized for both lead halides, with PbI2 films showing high texture compared to the reduced texture of the PbCl2 films. Large lateral grain sizes were observed for the PbI2 films with a flat platelet grain morphology and an average grain size up to 734.2 ± 144.8 nm. PbCl2 films have columnar grains with an average grain size up to 386.7 ± 119.5 nm. The PbI2 films showed a band gap of about 2.4 eV, confirming its semiconducting properties, and the PbCl2 had a wide band gap of 4.3 eV, which shows the insulating properties of this material.
Fungal Degradation of Wood: Emerging Data, New Insights and Changing Perceptions
Authors: Goodell Barry , Winandy Jerrold E. , Morrell Jeffrey J.
Published: December 2020

Wood durability researchers have long described fungal decay of timber using the starkly simple terms of white, brown and soft rot, along with the less destructive mold and stain fungi. These terms have taken on an almost iconic meaning but are only based upon the outward appearance of the damaged timber. Long-term deterioration studies, as well as the emerging genetic tools, are showing the fallacy of simplifying the decay process into such broad groups. This paper briefly reviews the fundamentals of fungal decay, staining and mold processes, then uses these fundamentals as the basis for a discussion of fungal attack of wood in light of current knowledge about these processes. Biotechnological applications of decay fungi are reviewed, and an overview is presented on how fungi surmount the protective barriers that coatings provide on surfaces. Advances in biochemical analyses have, in some cases, radically altered our perceptions of how wood is degraded, and even the relationships between fungal species, while other new findings have reinforced traditional perspectives. Suggestions for future research needs in the coatings field relative to enhanced fungal and environmental protection are presented.
Dynamic Contact Analysis of the Piston and Slipper Pair in Axial Piston Pump
Authors: Shen Hui , Zhou Zhuxin , Guan Dong , Liu Zhongtao , Jing Li , Zhang Chun
Published: December 2020

The dynamic analysis model of axial piston pump was established; both the kinematics and dynamics simulation analysis were conducted by virtual prototyping approach. The displacement, velocity, acceleration and stress curves of the piston under different working conditions were investigated. In addition, a ball-in-socket contact model was established, and the effects of hydraulic pressure, piston radius and radial clearance on normal displacement, contact radius, maximum contact pressure, normal contact stiffness and tangential contact stiffness were analyzed comprehensively. The results indicate that the normal displacement, maximum contact pressure, contact radius, normal contact stiffness and tangential contact stiffness can be improved by enlarging the piston radius and decreasing the radial clearance.
Preliminary Studies on an Innovative Bioactive Skin Soluble Beauty Mask Made by Combining Electrospinning and Dry Powder Impregnation
Authors: Teno Jorge , Pardo-Figuerez María , Hummel Nancy , Bonin Vincent , Fusco Alessandra , Ricci Claudio , Donnarumma Giovanna , Coltelli Maria-Beatrice , Danti Serena , Lagaron Jose María
Published: December 2020

The world of cosmetics is now aiming at biobased materials which are skin-compatible and can be used to generate more sustainable beauty masks with enhanced bioactivity. This work presents, in this line of interest, the combination of two innovative technologies, namely electrospinning and dry powder impregnation, to generate biobased skin soluble electrospun pullulan carriers dry impregnated with chitin nanofibrils-nanolignin-glycyrrethinic acid (CLA) complexes, as effective biobased and skin compatible beauty masks. The scalability of the pullulan electrospun carrier and bioactive complexes impregnation were optimized and the morphology evaluated. Subsequently, skin compatibility and mask effectiveness were investigated in vitro and in vivo. The results showed that cell viability was optimal for both impregnated and neat pullulan fibers. Additionally, the CLA impregnated pullulan fibers were able to upregulate the endogenous antimicrobial molecule HBD-2. Preliminary studies in vivo indicated that the beauty mask containing the CLA complexes significantly decreased area, length and depth of forehead and crow’s feet wrinkles, and significantly increased moisturizing levels in the skin. The developed beauty mask was also seen to increase skin firmness, while it did not show skin irritation after the test. The work demonstrates that the combination of these two technologies may open new alternatives to more sustainable bioactive cosmetic products for the skin.
Cemp1-p3 Peptide Promotes the Transformation of Octacalcium Phosphate into Hydroxyapatite Crystals
Authors: Santana Maricela , Montoya Gonzalo , Herrera Raúl , Hoz Lía , Romo Enrique , Zamora Claudia , Wintergerst Ana , Arzate Higinio
Published: December 2020

Dental cementum contains unique molecules that regulate the mineralization process in vitro and in vivo, such as cementum protein 1 (CEMP1). This protein possesses amino acid sequence motifs like the human recombinant CEMP1 with biological activity. This novel cementum protein 1-derived peptide (CEMP1-p3, from the CEMP1’s N-terminal domain: (QPLPKGCAAVKAEVGIPAPH), consists of 20 amino acids. Hydroxyapatite (HA) crystals could be obtained through the combination of the amorphous precursor phase and macromolecules such as proteins and peptides. We used a simple method to synthesize peptide/hydroxyapatite nanocomposites using OCP and CEMP1-p3. The characterization of the crystals through scanning electron microscopy (SEM), powder X-ray diffraction (XRD), high--resolution transmission electron microscopy (HRTEM), and Raman spectroscopy revealed that CEMP1-p3 transformed OCP into hydroxyapatite (HA) under constant ionic strength and in a buffered solution. CEMP1-p3 binds and highly adsorbs to OCP and is a potent growth stimulator of OCP crystals. CEMP1-p3 fosters the transformation of OCP into HA crystals with crystalline planes (300) and (004) that correspond to the cell of hexagonal HA. Octacalcium phosphate crystals treated with CEMP1-p3 grown in simulated physiological buffer acquired hexagonal arrangement corresponding to HA. These findings provide new insights into the potential application of CEMP1-p3 on possible biomimetic approaches to generate materials for the repair and regeneration of mineralized tissues, or restorative materials in the orthopedic field.
Synthesis by Hydrothermal Treatment of ZnO-Based Varistors Doped with Rare Earth Oxides and Their Characterization by Impedance Spectroscopy
Authors: Porcayo-Calderon J. , Ramos-Hernandez J.J. , Arrieta-Gonzalez C.D. , Chacon-Nava J.G. , Gonzalez-Rodriguez J.G. , Porcayo-Palafox E. , Sanchez-Carrillo M. , Flores-De los Rios J.P. , Martinez-Gomez L.
Published: December 2020

ZnO-based ceramic varistors have shown excellent electrical and dielectric properties due to their characteristics microstructures represented by the arrangement of their grains and grain boundaries that allow the absorption and flow of energy when subjected to an electrical surge. Their properties and characteristics depend on their chemical compositions and processing routes. Typical processing routes involve several stages of grinding and precalcination—which are time consuming processes. Because of this, this study proposes a simpler and cheaper alternative route for processing ceramic varistors. The alternative process proposed is the mixing of the precursor oxides by means of a hydrothermal treatment. The characteristics and properties of the synthesized ceramic varistors were evaluated by means of scanning electron microscopy, X-ray diffraction and impedance spectroscopy, considering the effect of the addition of rare earth oxides (La2O3, CeO2 and Nd2O3). The results showed that the mixing of the oxides through hydrothermal treatment produces ceramic varistors with characteristics and properties similar to those obtained by other processing routes. Furthermore, it was observed that the addition of rare earth oxides affects the characteristics and properties of the ceramic varistor depending on the type of rare earth oxide added, its concentration and ionic radius.
Not Cleaving the His-tag of Thal Results in More Tightly Packed and Better-Diffracting Crystals
Authors: Moritzer Ann-Christin , Prior Tina , Niemann Hartmut H.
Published: December 2020

Flavin-dependent halogenases chlorinate or brominate their substrates in an environmentally friendly manner, only requiring the cofactor reduced flavin adenine dinucleotide (FADH2), oxygen, and halide salts. The tryptophan 6-halogenase Thal exhibits two flexible loops, which become ordered (substrate-binding loop) or adopt a closed conformation (FAD loop) upon substrate or cofactor binding. Here, we describe the structure of NHis-Thal-RebH5 containing an N-terminal His-tag from pET28a, which crystallized in a different space group (P21) and, surprisingly, diffracted to a higher resolution of 1.63 Å than previously deposited Thal structures (P64; ~2.2 Å) with cleaved His-tag. Interestingly, the binding of glycine in the active site can induce an ordered conformation of the substrate-binding loop.
Crystal Structure and Spectroscopic Analysis of the Compatible Solute Nγ-Acetyl-L-2,4-Diaminobutyric Acid
Authors: Martin Lea , Klein Wilhelm , Schwaminger Sebastian P. , Fässler Thomas F. , Berensmeier Sonja
Published: December 2020

Compatible solutes are low molecular weight, highly water-soluble and neutrally net-charged molecules with various protective functionalities that accumulate and are produced in microorganisms. Their multi-purpose functionalities, also adaptable in vitro, make them potential components in healthcare and cosmetic products. One promising but insufficiently examined representative of this molecule class is Nγ-acetyl-L-2,4-diaminobutyric acid (γ-NADA), the metabolic precursor of ectoine. Here, we demonstrate the crystallization ability of γ-NADA by using cooling crystallization in aqueous solvents and find that it forms rod-shaped crystals. According to a single crystal structure determination, γ-NADA is orthorhombic with space group P212121 and a = 5.3647(1), b = 8.3652(2), c = 16.9149(5) Å, Z = 4, R1 = 3.48%, wR2 = 7.33% (all data). Additionally, γ-NADA is analyzed via Raman, IR, 1H, and 13C NMR spectroscopy.
Enhancement of Crystallization Behaviors in Quaternary Composites Containing Biodegradable Polymer by Supramolecular Inclusion Complex
Authors: Lee Li-Ting , He Sheng-Ping , Huang Chih-Feng
Published: December 2020

Novel multi-component composites composed of the biodegradable polymer poly(ethylene adipate) (PEA), the water-soluble polymer poly(ethylene oxide) (PEO), poly(vinyl acetate) (PVAc), and a supramolecular-like inclusion complex (IC) made by α-cyclodextrin (α-CD) and poly(ε-caprolactone) (PCL) (coded as PCL–CD–IC) are discussed in this work. The PCL–CD–IC was used to increase the crystallization rate of the miscible PEA/PEO/PVAc ternary blend that crystalized slower than neat PEA. Higher resolution SEM and TEM images displayed that PCL–CD–IC did not assemble notably in the quaternary composites. For the results of isothermal crystallization, the analysis of the Avrami equation demonstrated that the rate constant k increased with the addition of PCL–CD–IC in the composites, suggesting that PCL–CD–IC provided more nucleation sites to promote the crystallization rate. The nucleation density increased with the addition of PCL–CD–IC, and the amount of spherulite also increased. Wide angle X-ray results showed that the composites displayed similar diffraction patterns to neat PEA, meaning PEO, PVAc, and PCL–CD–IC would not change the crystal structures of PEA in the composites. The PCL–CD–IC, the supramolecular nucleation agent, demonstrated its superior ability to enhance the multi-component composites of biodegradable polymer in this study.
Primary Central Nervous System Lymphomas: A Diagnostic Overview of Key Histomorphologic, Immunophenotypic, and Genetic Features
Authors: Lauw Marietya I. S. , Lucas Calixto-Hope G. , Ohgami Robert S. , Wen Kwun Wah
Published: December 2020

Primary central nervous system lymphoma (PCNSL) is a rare form of extranodal non-Hodgkin lymphoma that primarily arises in the brain, spinal cord, leptomeninges, and vitreoretinal compartment of the eye. The term is sometimes used interchangeably with primary central nervous system diffuse large B-cell lymphoma (PCNS DLBCL) because DLBCL comprises a great majority (90–95%) of PCNSL. Although rare, other types of lymphomas can be seen in the central nervous system (CNS), and familiarity with these entities will help their recognition and further workup in order to establish the diagnosis. The latter is especially important in the case of PCNSL where procurement of diagnostic specimen is often challenging and yields scant tissue. In this review, we will discuss the most common types of primary lymphomas that can be seen in the CNS with emphasis on the diagnostic histomorphologic, immunophenotypic, and molecular genetic features. The differential diagnostic approach to these cases and potential pitfalls will also be discussed.
Reconstructing Nonparametric Productivity Networks
Authors: Bostian Moriah B. , Daraio Cinzia , Färe Rolf , Grosskopf Shawna , Izzo Maria Grazia , Leuzzi Luca , Ruocco Giancarlo , Weber William L.
Published: December 2020

Network models provide a general representation of inter-connected system dynamics. This ability to connect systems has led to a proliferation of network models for economic productivity analysis, primarily estimated non-parametrically using Data Envelopment Analysis (DEA). While network DEA models can be used to measure system performance, they lack a statistical framework for inference, due in part to the complex structure of network processes. We fill this gap by developing a general framework to infer the network structure in a Bayesian sense, in order to better understand the underlying relationships driving system performance. Our approach draws on recent advances in information science, machine learning and statistical inference from the physics of complex systems to estimate unobserved network linkages. To illustrate, we apply our framework to analyze the production of knowledge, via own and cross-disciplinary research, for a world-country panel of bibliometric data. We find significant interactions between related disciplinary research output, both in terms of quantity and quality. In the context of research productivity, our results on cross-disciplinary linkages could be used to better target research funding across disciplines and institutions. More generally, our framework for inferring the underlying network production technology could be applied to both public and private settings which entail spillovers, including intra- and inter-firm managerial decisions and public agency coordination. This framework also provides a systematic approach to model selection when the underlying network structure is unknown.
Assessment of Nocturnal Autonomic Cardiac Imbalance in Positional Obstructive Sleep Apnea. A Multiscale Nonlinear Approach
Authors: Álvarez Daniel , Arroyo C. Ainhoa , de Frutos Julio F. , Crespo Andrea , Cerezo-Hernández Ana , Gutiérrez-Tobal Gonzalo C. , Vaquerizo-Villar Fernando , Barroso-García Verónica , Moreno Fernando , Ruiz Tomás , Hornero Roberto , del Campo Félix
Published: December 2020

Positional obstructive sleep apnea (POSA) is a major phenotype of sleep apnea. Supine-predominant positional patients are frequently characterized by milder symptoms and less comorbidity due to a lower age, body mass index, and overall apnea-hypopnea index. However, the bradycardia-tachycardia pattern during apneic events is known to be more severe in the supine position, which could affect the cardiac regulation of positional patients. This study aims at characterizing nocturnal heart rate modulation in the presence of POSA in order to assess potential differences between positional and non-positional patients. Patients showing clinical symptoms of suffering from a sleep-related breathing disorder performed unsupervised portable polysomnography (PSG) and simultaneous nocturnal pulse oximetry (NPO) at home. Positional patients were identified according to the Amsterdam POSA classification (APOC) criteria. Pulse rate variability (PRV) recordings from the NPO readings were used to assess overnight cardiac modulation. Conventional cardiac indexes in the time and frequency domains were computed. Additionally, multiscale entropy (MSE) was used to investigate the nonlinear dynamics of the PRV recordings in POSA and non-POSA patients. A total of 129 patients (median age 56.0, interquartile range (IQR) 44.8–63.0 years, median body mass index (BMI) 27.7, IQR 26.0–31.3 kg/m2) were classified as POSA (37 APOC I, 77 APOC II, and 15 APOC III), while 104 subjects (median age 57.5, IQR 49.0–67.0 years, median BMI 29.8, IQR 26.6–34.7 kg/m2) comprised the non-POSA group. Overnight PRV recordings from positional patients showed significantly higher disorderliness than non-positional subjects in the smallest biological scales of the MSE profile (τ = 1: 0.25, IQR 0.20–0.31 vs. 0.22, IQR 0.18–0.27, p < 0.01) (τ = 2: 0.41, IQR 0.34–0.48 vs. 0.37, IQR 0.29–0.42, p < 0.01). According to our findings, nocturnal heart rate regulation is severely affected in POSA patients, suggesting increased cardiac imbalance due to predominant positional apneas.
A Robust Solution to Variational Importance Sampling of Minimum Variance
Authors: Hernández-González Jerónimo , Cerquides Jesús
Published: December 2020

Importance sampling is a Monte Carlo method where samples are obtained from an alternative proposal distribution. This can be used to focus the sampling process in the relevant parts of space, thus reducing the variance. Selecting the proposal that leads to the minimum variance can be formulated as an optimization problem and solved, for instance, by the use of a variational approach. Variational inference selects, from a given family, the distribution which minimizes the divergence to the distribution of interest. The Rényi projection of order 2 leads to the importance sampling estimator of minimum variance, but its computation is very costly. In this study with discrete distributions that factorize over probabilistic graphical models, we propose and evaluate an approximate projection method onto fully factored distributions. As a result of our evaluation it becomes apparent that a proposal distribution mixing the information projection with the approximate Rényi projection of order 2 could be interesting from a practical perspective.
Identification of the Framingham Risk Score by an Entropy-Based Rule Model for Cardiovascular Disease
Authors: Chen You-Shyang , Cheng Ching-Hsue , Chen Su-Fen , Jhuang Jhe-You
Published: December 2020

Since 2001, cardiovascular disease (CVD) has had the second-highest mortality rate, about 15,700 people per year, in Taiwan. It has thus imposed a substantial burden on medical resources. This study was triggered by the following three factors. First, the CVD problem reflects an urgent issue. A high priority has been placed on long-term therapy and prevention to reduce the wastage of medical resources, particularly in developed countries. Second, from the perspective of preventive medicine, popular data-mining methods have been well learned and studied, with excellent performance in medical fields. Thus, identification of the risk factors of CVD using these popular techniques is a prime concern. Third, the Framingham risk score is a core indicator that can be used to establish an effective prediction model to accurately diagnose CVD. Thus, this study proposes an integrated predictive model to organize five notable classifiers: the rough set (RS), decision tree (DT), random forest (RF), multilayer perceptron (MLP), and support vector machine (SVM), with a novel use of the Framingham risk score for attribute selection (i.e., F-attributes first identified in this study) to determine the key features for identifying CVD. Verification experiments were conducted with three evaluation criteria—accuracy, sensitivity, and specificity—based on 1190 instances of a CVD dataset available from a Taiwan teaching hospital and 2019 examples from a public Framingham dataset. Given the empirical results, the SVM showed the best performance in terms of accuracy (99.67%), sensitivity (99.93%), and specificity (99.71%) in all F-attributes in the CVD dataset compared to the other listed classifiers. The RS showed the highest performance in terms of accuracy (85.11%), sensitivity (86.06%), and specificity (85.19%) in most of the F-attributes in the Framingham dataset. The above study results support novel evidence that no classifier or model is suitable for all practical datasets of medical applications. Thus, identifying an appropriate classifier to address specific medical data is important. Significantly, this study is novel in its calculation and identification of the use of key Framingham risk attributes integrated with the DT technique to produce entropy-based decision rules of knowledge sets, which has not been undertaken in previous research. This study conclusively yielded meaningful entropy-based knowledgeable rules in tree structures and contributed to the differentiation of classifiers from the two datasets with three useful research findings and three helpful management implications for subsequent medical research. In particular, these rules provide reasonable solutions to simplify processes of preventive medicine by standardizing the formats and codes used in medical data to address CVD problems. The specificity of these rules is thus significant compared to those of past research.
Cultural Dimension in Internationalization of the Curriculum in Higher Education
Authors: Sá Maria José , Serpa Sandro
Published: December 2020

Internationalization in higher education seems to be an unavoidable process, albeit temporarily limited by the COVID-19 (coronavirus disease of 2019) pandemic. Specifically, internationalization of the curriculum in the context of higher education is a dimension of this internationalization that is less valued in published studies. This paper, through critical reflection, sought to contribute to a deeper understanding of internationalization of the curriculum in higher education. The methodology used consisted of a bibliographic search in international databases, and the selected documents were analyzed using the content analysis technique. This analysis allowed concluding that internationalization of the curriculum in higher education is a complex process and involves several actors, with various challenges to be considered. For this process to be successful, it involves the ability to be attentive to the cultural multiplicity that will be experienced in classes where this internationalization of the curriculum exists.
Improving Graduation Rate Estimates Using Regularly Updating Multi-Level Absorbing Markov Chains
Authors: Boumi Shahab , Vela Adan Ernesto
Published: December 2020

American universities use a procedure based on a rolling six-year graduation rate to calculate statistics regarding their students’ final educational outcomes (graduating or not graduating). As an alternative to the six-year graduation rate method, many studies have applied absorbing Markov chains for estimating graduation rates. In both cases, a frequentist approach is used. For the standard six-year graduation rate method, the frequentist approach corresponds to counting the number of students who finished their program within six years and dividing by the number of students who entered that year. In the case of absorbing Markov chains, the frequentist approach is used to compute the underlying transition matrix, which is then used to estimate the graduation rate. In this paper, we apply a sensitivity analysis to compare the performance of the standard six-year graduation rate method with that of absorbing Markov chains. Through the analysis, we highlight significant limitations with regards to the estimation accuracy of both approaches when applied to small sample sizes or cohorts at a university. Additionally, we note that the Absorbing Markov chain method introduces a significant bias, which leads to an underestimation of the true graduation rate. To overcome both these challenges, we propose and evaluate the use of a regularly updating multi-level absorbing Markov chain (RUML-AMC) in which the transition matrix is updated year to year. We empirically demonstrate that the proposed RUML-AMC approach nearly eliminates estimation bias while reducing the estimation variation by more than 40%, especially for populations with small sample sizes.
Trade-Offs for the Optimal Energy Efficiency of Road Transportation: Domestic Cases in Developing Countries
Authors: Akbar Usman , Khan Muhammad Asif , Akmal Marryum , Tóth Naárné Éva Zsuzsanna , Oláh Judit
Published: December 2020

The increase in domestic transportation in developing countries may adversely affect the energy efficiency of road transportation due to effective productivity and carbon dioxide emissions (CO2). When evaluating quantitatively the countries on the efficiency frontier, poor efficiency can still be seen sometimes due to the slack available in undesirable output measures. This paper uses desirable and undesirable output variables, such as passenger-kilometers (PKM), tones-kilometers (TKM), and carbon dioxide (CO2), to compute the weakly efficient decision-making units (DMUs). The data envelopment analysis (DEA) technology is used to assess the efficiencies of the decision-making units (DMUs), which are countries in our case. Then, the trade-off method with efficient binding surfaces is used to attain the optimal efficiencies of the weakly efficient DMUs. The marginal rates aid this trade-off analysis. Resultantly, such marginal trade-offs do not deteriorate the efficiency of the DMUs below the frontier line. We calculate the maximum change (margin) in a specific variable amount when another variable’s amount is changed. Thus, such a computation gives us different margins, with which each output variable can be a traded off to bring a DMU further toward the closest optimal point possible. The marginal trade-off can help the managers and policymakers in effective decision-making, and it is further recommended to address efficiency damages (by the undesired outputs).