bluuebunny/crossref_metadata_2025 huggingface dataset:
Mycosis Fungoides and Sézary Syndrome: An Integrative Review of the Pathophysiology, Molecular Drivers, and Targeted Therapy
Authors: García-Díaz Nuria , Piris Miguel Ángel , Ortiz-Romero Pablo Luis , Vaqué José Pedro
Published: April 2021

Primary cutaneous T-cell lymphomas (CTCLs) constitute a heterogeneous group of diseases that affect the skin. Mycosis fungoides (MF) and Sézary syndrome (SS) account for the majority of these lesions and have recently been the focus of extensive translational research. This review describes and discusses the main pathobiological manifestations of MF/SS, the molecular and clinical features currently used for diagnosis and staging, and the different therapies already approved or under development. Furthermore, we highlight and discuss the main findings illuminating key molecular mechanisms that can act as drivers for the development and progression of MF/SS. These seem to make up an orchestrated constellation of genomic and environmental alterations generated around deregulated T-cell receptor (TCR)/phospholipase C, gamma 1, (PLCG1) and Janus kinase/ signal transducer and activator of transcription (JAK/STAT) activities that do indeed provide us with novel opportunities for diagnosis and therapy.
CD80 Expression on Tumor Cells Alters Tumor Microenvironment and Efficacy of Cancer Immunotherapy by CTLA-4 Blockade
Authors: Vackova Julie , Polakova Ingrid , Johari Shweta Dilip , Smahel Michal
Published: April 2021

Cluster of differentiation (CD) 80 is mainly expressed in immune cells but can also be found in several types of cancer cells. This molecule may either activate or inhibit immune reactions. Here, we determined the immunosuppressive role of CD80 in the tumor microenvironment by CRISPR/Cas9-mediated deactivation of the corresponding gene in the mouse oncogenic TC-1 cell line. The tumor cells with deactivated CD80 (TC-1/dCD80-1) were more immunogenic than parental cells and induced tumors that gained sensitivity to cytotoxic T-lymphocyte antigen 4 (CTLA-4) blockade, as compared with the TC-1 cells. In vivo depletion experiments showed that the deactivation of CD80 switched the pro-tumorigenic effect of macrophages observed in TC-1-induced tumors into an anti-tumorigenic effect in TC-1/dCD80-1 tumors and induced the pro-tumorigenic activity of CD4+ cells. Moreover, the frequency of lymphoid and myeloid cells and the CTLA-4 expression by T helper (Th)17 cells were increased in TC-1/dCD80-1- compared with that in the TC-1-induced tumors. CTLA-4 blockade downregulated the frequencies of most immune cell types and upregulated the frequency of M2 macrophages in the TC-1 tumors, while it increased the frequency of lymphoid cells in TC-1/dCD80-1-induced tumors. Furthermore, the anti-CTLA-4 therapy enhanced the frequency of CD8+ T cells as well as CD4+ T cells, especially for a Th1 subset. Regulatory T cells (Treg) formed the most abundant CD4+ T cell subset in untreated tumors. The anti-CTLA-4 treatment downregulated the frequency of Treg cells with limited immunosuppressive potential in the TC-1 tumors, whereas it enriched this type of Treg cells and decreased the Treg cells with high immunosuppressive potential in TC-1/dCD80-1-induced tumors. The immunosuppressive role of tumor-cell-expressed CD80 should be considered in research into biomarkers for the prediction of cancer patients’ sensitivity to immune checkpoint inhibitors and for the development of a tumor-cell-specific CD80 blockade.
Multicenter Analysis of Treatment Outcomes for Systemic Therapy in Well Differentiated Grade 3 Neuroendocrine Tumors (NET G3)
Authors: Apostolidis Leonidas , Dal Buono Arianna , Merola Elettra , Jann Henning , Jäger Dirk , Wiedenmann Bertram , Winkler Eva Caroline , Pavel Marianne
Published: April 2021

Well-differentiated grade 3 neuroendocrine tumors (NET G3) have been distinguished from poorly differentiated neuroendocrine carcinomas (NEC) in the most current WHO classifications. Commonly applied first-line chemotherapy protocols with cisplatin or carboplatin in combination with etoposide (PE) are less effective in NET G3 than NEC. Suggested alternative treatment protocols have not been studied in first-line therapy of NET G3 so far. We performed a retrospective analysis of patients with NET G3 in the databases of 3 German cancer centers. Out of 142 patients, 136 patients received palliative first-line therapy: overall response rate (ORR) was 35.1% for PE (n = 37), 56.4% for FOLFOX (n = 39), 27.3% for temozolomide/capecitabine (TEM/CAP) (n = 22), 45.0% for streptozotocin/5-fluorouracil (STZ/5-FU) (n = 20), and 16.7% for other (n = 18). Median progression-free survival (PFS) for PE was 6.9 months. Compared to PE, PFS in the other treatment groups was 6.9 months for FOLFOX (p = 0.333), 12.0 months for TEM/CAP (p = 0.093), 4.8 months for STZ/5-FU (p = 0.919), and 14.1 months for other (p = 0.014). In a univariate setting, all non-PE patients combined showed a significantly prolonged PFS vs. PE (9.0 months; p = 0.049) which could not be confirmed in a multivariate analysis. In conclusion, NET G3 with FOLFOX showed the highest ORR, and with TEM/CAP showed the longest PFS. Further prospective evaluation of the optimal therapeutic strategy for this tumor entity is needed.
New Therapeutic Strategies for Lung Cancer
Authors: Icard Philippe , Damotte Diane , Alifano Marco
Published: April 2021

Non-small cell lung cancer (NSCLC) accounts for approximately 27% of all cancer-related deaths worldwide, thus representing a major health problem [...]
UV Stimulated Manganese Dioxide for the Persulfate Catalytic Degradation of Bisphenol A
Authors: Dong Guihua , Chen Bing , Liu Bo , Stoyanov Stanislav R. , Cao Yiqi , Yang Min , Zhang Baiyu
Published: April 2021

One of the most commonly produced industrial chemicals worldwide, bisphenol A (BPA), is used as a precursor in plastics, resins, paints, and many other materials. It has been proved that BPA can cause long-term adverse effects on ecosystems and human health due to its toxicity as an endocrine disruptor. In this study, we developed an integrated MnO2/UV/persulfate (PS) process for use in BPA photocatalytic degradation from water and examined the reaction mechanisms, degradation pathways, and toxicity reduction. Comparative tests using MnO2, PS, UV, UV/MnO2, MnO2/PS, and UV/PS processes were conducted under the same conditions to investigate the mechanism of BPA catalytic degradation by the proposed MnO2/UV/PS process. The best performance was observed in the MnO2/UV/PS process in which BPA was completely removed in 30 min with a reduction rate of over 90% for total organic carbon after 2 h. This process also showed a stable removal efficiency with a large variation of pH levels (3.6 to 10.0). Kinetic analysis suggested that 1O2 and SO4•− played more critical roles than •OH for BPA degradation. Infrared spectra showed that UV irradiation could stimulate the generation of –OH groups on the MnO2 photocatalyst surface, facilitating the PS catalytic degradation of BPA in this process. The degradation pathways were further proposed in five steps, and thirteen intermediates were identified by gas chromatography-mass spectrometry. The acute toxicity was analyzed during the treatment, showing a slight increase (by 3.3%) in the first 30 min and then a decrease by four-fold over 2 h. These findings help elucidate the mechanism and pathways of BPA degradation and provide an effective PS catalytic strategy.
Removal of VOCs by Ozone: n-Alkane Oxidation under Mild Conditions
Authors: Mytareva Alina I. , Mashkovsky Igor S. , Kanaev Sergey A. , Bokarev Dmitriy A. , Baeva Galina N. , Kazakov Alexander V. , Stakheev Alexander Yu.
Published: April 2021

Volatile organic compounds (VOCs) have a negative effect on both humans and the environment; therefore, it is crucial to minimize their emission. The conventional solution is the catalytic oxidation of VOCs by air; however, in some cases this method requires relatively high temperatures. Thus, the oxidation of short-chain alkanes, which demonstrate the lowest reactivity among VOCs, starts at 250–350 °C. This research deals with the ozone catalytic oxidation (OZCO) of alkanes at temperatures as low as 25–200 °C using an alumina-supported manganese oxide catalyst. Our data demonstrate that oxidation can be significantly accelerated in the presence of a small amount of O3. In particular, it was found that n-C4H10 can be readily oxidized by an air/O3 mixture over the Mn/Al2O3 catalyst at temperatures as low as 25 °C. According to the characterization data (SEM-EDX, XRD, H2-TPR, and XPS) the superior catalytic performance of the Mn/Al2O3 catalyst in OZCO stems from a high concentration of Mn2O3 species and oxygen vacancies.
Rho Family GTPases and Rho GEFs in Glucose Homeostasis
Authors: Machin Polly A. , Tsonou Elpida , Hornigold David C. , Welch Heidi C. E.
Published: April 2021

Dysregulation of glucose homeostasis leading to metabolic syndrome and type 2 diabetes is the cause of an increasing world health crisis. New intriguing roles have emerged for Rho family GTPases and their Rho guanine nucleotide exchange factor (GEF) activators in the regulation of glucose homeostasis. This review summates the current knowledge, focusing in particular on the roles of Rho GEFs in the processes of glucose-stimulated insulin secretion by pancreatic β cells and insulin-stimulated glucose uptake into skeletal muscle and adipose tissues. We discuss the ten Rho GEFs that are known so far to regulate glucose homeostasis, nine of which are in mammals, and one is in yeast. Among the mammalian Rho GEFs, P-Rex1, Vav2, Vav3, Tiam1, Kalirin and Plekhg4 were shown to mediate the insulin-stimulated translocation of the glucose transporter GLUT4 to the plasma membrane and/or insulin-stimulated glucose uptake in skeletal muscle or adipose tissue. The Rho GEFs P-Rex1, Vav2, Tiam1 and β-PIX were found to control the glucose-stimulated release of insulin by pancreatic β cells. In vivo studies demonstrated the involvement of the Rho GEFs P-Rex2, Vav2, Vav3 and PDZ-RhoGEF in glucose tolerance and/or insulin sensitivity, with deletion of these GEFs either contributing to the development of metabolic syndrome or protecting from it. This research is in its infancy. Considering that over 80 Rho GEFs exist, it is likely that future research will identify more roles for Rho GEFs in glucose homeostasis.
Inflammasome Activation-Induced Hypercoagulopathy: Impact on Cardiovascular Dysfunction Triggered in COVID-19 Patients
Authors: Gedefaw Lealem , Ullah Sami , Leung Polly H. M. , Cai Yin , Yip Shea-Ping , Huang Chien-Ling
Published: April 2021

Coronavirus disease 2019 (COVID-19) is the most devastating infectious disease in the 21st century with more than 2 million lives lost in less than a year. The activation of inflammasome in the host infected by SARS-CoV-2 is highly related to cytokine storm and hypercoagulopathy, which significantly contribute to the poor prognosis of COVID-19 patients. Even though many studies have shown the host defense mechanism induced by inflammasome against various viral infections, mechanistic interactions leading to downstream cellular responses and pathogenesis in COVID-19 remain unclear. The SARS-CoV-2 infection has been associated with numerous cardiovascular disorders including acute myocardial injury, myocarditis, arrhythmias, and venous thromboembolism. The inflammatory response triggered by the activation of NLRP3 inflammasome under certain cardiovascular conditions resulted in hyperinflammation or the modulation of angiotensin-converting enzyme 2 signaling pathways. Perturbations of several target cells and tissues have been described in inflammasome activation, including pneumocytes, macrophages, endothelial cells, and dendritic cells. The interplay between inflammasome activation and hypercoagulopathy in COVID-19 patients is an emerging area to be further addressed. Targeted therapeutics to suppress inflammasome activation may have a positive effect on the reduction of hyperinflammation-induced hypercoagulopathy and cardiovascular disorders occurring as COVID-19 complications.
Role of MicroRNA-145 in DNA Damage Signalling and Senescence in Vascular Smooth Muscle Cells of Type 2 Diabetic Patients
Authors: Hemmings Karen E. , Riches-Suman Kirsten , Bailey Marc A. , O’Regan David J. , Turner Neil A. , Porter Karen E.
Published: April 2021

Increased cardiovascular morbidity and mortality in individuals with type 2 diabetes (T2DM) is a significant clinical problem. Despite advancements in achieving good glycaemic control, this patient population remains susceptible to macrovascular complications. We previously discovered that vascular smooth muscle cells (SMC) cultured from T2DM patients exhibit persistent phenotypic aberrancies distinct from those of individuals without a diagnosis of T2DM. Notably, persistently elevated expression levels of microRNA-145 co-exist with characteristics consistent with aging, DNA damage and senescence. We hypothesised that increased expression of microRNA-145 plays a functional role in DNA damage signalling and subsequent cellular senescence specifically in SMC cultured from the vasculature of T2DM patients. In this study, markers of DNA damage and senescence were unambiguously and permanently elevated in native T2DM versus non-diabetic (ND)-SMC. Exposure of ND cells to the DNA-damaging agent etoposide inflicted a senescent phenotype, increased expression of apical kinases of the DNA damage pathway and elevated expression levels of microRNA-145. Overexpression of microRNA-145 in ND-SMC revealed evidence of functional links between them; notably increased secretion of senescence-associated cytokines and chronic activation of stress-activated intracellular signalling pathways, particularly the mitogen-activated protein kinase, p38α. Exposure to conditioned media from microRNA-145 overexpressing cells resulted in chronic p38α signalling in naïve cells, evidencing a paracrine induction and reinforcement of cell senescence. We conclude that targeting of microRNA-145 may provide a route to novel interventions to eliminate DNA-damaged and senescent cells in the vasculature and to this end further detailed studies are warranted.
Sex-Biased lncRNA Signature in Fetal Growth Restriction (FGR)
Authors: Lipka Aleksandra , Jastrzebski Jan Pawel , Paukszto Lukasz , Makowczenko Karol Gustaw , Lopienska-Biernat Elzbieta , Gowkielewicz Marek , Lepiarczyk Ewa , Wiszpolska Marta , Majewski Mariusz Krzysztof , Majewska Marta
Published: April 2021

Impaired fetal growth is one of the most important causes of prematurity, stillbirth and infant mortality. The pathogenesis of idiopathic fetal growth restriction (FGR) is poorly understood but is thought to be multifactorial and comprise a range of genetic causes. This research aimed to investigate non-coding RNAs (lncRNAs) in the placentas of male and female fetuses affected by FGR. RNA-Seq data were analyzed to detect lncRNAs, their potential target genes and circular RNAs (circRNAs); a differential analysis was also performed. The multilevel bioinformatic analysis enabled the detection of 23,137 placental lncRNAs and 4263 of them were classified as novel. In FGR-affected female fetuses’ placentas (ff-FGR), among 19 transcriptionally active regions (TARs), five differentially expressed lncRNAs (DELs) and 12 differentially expressed protein-coding genes (DEGs) were identified. Within 232 differentially expressed TARs identified in male fetuses (mf-FGR), 33 encompassed novel and 176 known lncRNAs, and 52 DEGs were upregulated, while 180 revealed decreased expression. In ff-FGR ACTA2-AS1, lncRNA expression was significantly correlated with five DEGs, and in mf-FGR, 25 TARs were associated with DELs correlated with 157 unique DEGs. Backsplicing circRNA processes were detected in the range of H19 lncRNA, in both ff- and mf-FGR placentas. The performed global lncRNAs characteristics in terms of fetal sex showed dysregulation of DELs, DEGs and circRNAs that may affect fetus growth and pregnancy outcomes. In female placentas, DELs and DEGs were associated mainly with the vasculature, while in male placentas, disturbed expression predominantly affected immune processes.
Regulation of RNA Splicing: Aberrant Splicing Regulation and Therapeutic Targets in Cancer
Authors: Kitamura Koji , Nimura Keisuke
Published: April 2021

RNA splicing is a critical step in the maturation of precursor mRNA (pre-mRNA) by removing introns and exons. The combination of inclusion and exclusion of introns and exons in pre-mRNA can generate vast diversity in mature mRNA from a limited number of genes. Cancer cells acquire cancer-specific mechanisms through aberrant splicing regulation to acquire resistance to treatment and to promote malignancy. Splicing regulation involves many factors, such as proteins, non-coding RNAs, and DNA sequences at many steps. Thus, the dysregulation of splicing is caused by many factors, including mutations in RNA splicing factors, aberrant expression levels of RNA splicing factors, small nuclear ribonucleoproteins biogenesis, mutations in snRNA, or genomic sequences that are involved in the regulation of splicing, such as 5’ and 3’ splice sites, branch point site, splicing enhancer/silencer, and changes in the chromatin status that affect the splicing profile. This review focuses on the dysregulation of RNA splicing related to cancer and the associated therapeutic methods.
Coexistence of SOS-Dependent and SOS-Independent Regulation of DNA Repair Genes in Radiation-Resistant Deinococcus Bacteria
Authors: Blanchard Laurence , de Groot Arjan
Published: April 2021

Deinococcus bacteria are extremely resistant to radiation and able to repair a shattered genome in an essentially error-free manner after exposure to high doses of radiation or prolonged desiccation. An efficient, SOS-independent response mechanism to induce various DNA repair genes such as recA is essential for radiation resistance. This pathway, called radiation/desiccation response, is controlled by metallopeptidase IrrE and repressor DdrO that are highly conserved in Deinococcus. Among various Deinococcus species, Deinococcus radiodurans has been studied most extensively. Its genome encodes classical DNA repair proteins for error-free repair but no error-prone translesion DNA polymerases, which may suggest that absence of mutagenic lesion bypass is crucial for error-free repair of massive DNA damage. However, many other radiation-resistant Deinococcus species do possess translesion polymerases, and radiation-induced mutagenesis has been demonstrated. At least dozens of Deinococcus species contain a mutagenesis cassette, and some even two cassettes, encoding error-prone translesion polymerase DnaE2 and two other proteins, ImuY and ImuB-C, that are probable accessory factors required for DnaE2 activity. Expression of this mutagenesis cassette is under control of the SOS regulators RecA and LexA. In this paper, we review both the RecA/LexA-controlled mutagenesis and the IrrE/DdrO-controlled radiation/desiccation response in Deinococcus.
Expression and Function of ZEB1 in the Cornea
Authors: Zhang Yingnan , Liu Xiao , Liang Wei , Dean Douglas C. , Zhang Lijun , Liu Yongqing
Published: April 2021

ZEB1 is an important transcription factor for epithelial to mesenchymal transition (EMT) and in the regulation of cell differentiation and transformation. In the cornea, ZEB1 presents in all three layers: the epithelium, the stroma and the endothelium. Mutations of ZEB1 have been linked to multiple corneal genetic defects, particularly to the corneal dystrophies including keratoconus (KD), Fuchs endothelial corneal dystrophy (FECD), and posterior polymorphous corneal dystrophy (PPCD). Accumulating evidence indicates that dysfunction of ZEB1 may affect corneal stem cell homeostasis, and cause corneal cell apoptosis, stromal fibrosis, angiogenesis, squamous metaplasia. Understanding how ZEB1 regulates the initiation and progression of these disorders will help us in targeting ZEB1 for potential avenues to generate therapeutics to treat various ZEB1-related disorders.
The Role of Heparan Sulfate and Neuropilin 2 in VEGFA Signaling in Human Endothelial Tip Cells and Non-Tip Cells during Angiogenesis In Vitro
Authors: Dallinga Marchien G. , Habani Yasmin I. , Schimmel Alinda W. M. , Dallinga-Thie Geesje M. , van Noorden Cornelis J. F. , Klaassen Ingeborg , Schlingemann Reinier O.
Published: April 2021

During angiogenesis, vascular endothelial growth factor A (VEGFA) regulates endothelial cell (EC) survival, tip cell formation, and stalk cell proliferation via VEGF receptor 2 (VEGFR2). VEGFR2 can interact with VEGFR2 co-receptors such as heparan sulfate proteoglycans (HSPGs) and neuropilin 2 (NRP2), but the exact roles of these co-receptors, or of sulfatase 2 (SULF2), an enzyme that removes sulfate groups from HSPGs and inhibits HSPG-mediated uptake of very low density lipoprotein (VLDL), in angiogenesis and tip cell biology are unknown. In the present study, we investigated whether the modulation of binding of VEGFA to VEGFR2 by knockdown of SULF2 or NRP2 affects sprouting angiogenesis, tip cell formation, proliferation of non-tip cells, and EC survival, or uptake of VLDL. To this end, we employed VEGFA splice variant 121, which lacks an HSPG binding domain, and VEGFA splice variant 165, which does have this domain, in in vitro models of angiogenic tip cells and vascular sprouting. We conclude that VEGFA165 and VEGFA121 have similar inducing effects on tip cells and sprouting in vitro, and that the binding of VEGFA165 to HSPGs in the extracellular matrix does not seem to play a role, as knockdown of SULF2 did not alter these effects. Co-binding of NRP2 appears to regulate VEGFA–VEGFR2-induced sprout initiation, but not tip cell formation. Finally, as the addition of VLDL increased sprout formation but not tip cell formation, and as VLDL uptake was limited to non-tip cells, our findings suggest that VLDL plays a role in sprout formation by providing biomass for stalk cell proliferation.
Modeling and Experimental Investigations of Nanostructured Ag Thin Films Produced by Oblique-Angle Deposition and Its SERS Performance
Authors: Hui Datai , Zhou Shun , Cai Changlong , Song Shigeng , Wu Zhentao , Song Jian , Zhang Da , Meng Xiao , Lu Bo , Duan Yingbu , Tursun Hayrigul , Gibson Des
Published: April 2021

The growth mechanism of nanocolumnar silver thin film deposited on a smooth silicon substrate using electron beam evaporation process at an oblique angle was simulated with the Kinetic Monte Carlo method. Following the simulated silver nanostructured thin film, a further computational simulation was done using COMSOL for surface-enhanced Raman scattering effects. The simulation results were compared against corresponding experimental results, which demonstrated high agreement between simulation results and experimental data. It was found that as the incident deposition angle increased, the density of the Ag thin film significantly decreased and the surface roughness increased. When the incident deposition angle was at 75° and 85°, the resulting nanocolumnar structure was significantly tilted. For Ag thin films deposited at all investigated angles, surface-enhanced Raman scattering effects were observed. Particularly, the Ag nanocolumns deposited at 85° showed remarkable Surface-enhanced Raman Scattering effects. This was seen in both COMSOL simulations and experimental results: Enhancement factors were 2 × 107 in COMSOL simulation and 3.3 × 105 in the experiment.
A Dual Active-Passive Coating with Intumescent and Fire-Retardant Properties Based on High Molecular Weight Tannins
Authors: Solis-Pomar Francisco , Díaz-Gómez Andrés , Berrío María Elizabeth , Ramírez Jesús , Jaramillo Andrés Felipe , Fernández Katherina , Rojas David , Melendrez Manuel Francisco , Pérez-Tijerina Eduardo
Published: April 2021

In this study, the tannins extracted from the Pinus radiata bark were used to develop an active–passive dual paint scheme with intumescent (IN) and fire-resistant (FR) behaviors. The properties of the coating were observed to depend on the concentration of high-molecular-weight tannins (H-MWT) incorporated into the formulation. At high concentrations (13% w/w), the coating exhibits fire-retardant properties due to the generation of a carbonaceous layer; however, at low concentrations (2.5% w/w), it generates an intumescent effect due to the formation of a carbonaceous foam layer. The dual IN–FR scheme was evaluated against fire by flame advance tests, carbonization index, mass loss, and intumescent effect, and was also compared to a commercial coating. The dual scheme presented good mechanical properties with a pull-off adhesion value of 0.76 MPa and an abrasion index of 54.7% at 1000 cycles, when using a coating with a high solid content (>60%) and the same thickness as those of the commercial coatings. The results of the fire resistance test indicate that the dual scheme generates a protective effect for wood and metal, with an excellent performance that is comparable to that of a commercial intumescent coating.
Attachment and Growth of Fibroblast Cells on Poly (2-Methoxyethyl Acrylate) Analog Polymers as Coating Materials
Authors: Anjum Rubaiya , Nishida Kei , Matsumoto Haruka , Murakami Daiki , Kobayashi Shingo , Anada Takahisa , Tanaka Masaru
Published: April 2021

The regulation of adhesion and the subsequent behavior of fibroblast cells on the surface of biomaterials is important for successful tissue regeneration and wound healing by implanted biomaterials. We have synthesized poly(ω-methoxyalkyl acrylate)s (PMCxAs; x indicates the number of methylene carbons between the ester and ethyl oxygen), with a carbon chain length of x = 2–6, to investigate the regulation of fibroblast cell behavior including adhesion, proliferation, migration, differentiation and collagen production. We found that PMC2A suppressed the cell spreading, protein adsorption, formation of focal adhesion, and differentiation of normal human dermal fibroblasts, while PMC4A surfaces enhanced them compared to other PMCxAs. Our findings suggest that fibroblast activities attached to the PMCxA substrates can be modified by changing the number of methylene carbons in the side chains of the polymers. These results indicate that PMCxAs could be useful coating materials for use in skin regeneration and wound dressing applications.
Investigation of Spin Coating Cerium-Doped Hydroxyapatite Thin Films with Antifungal Properties
Authors: Iconaru Simona Liliana , Predoi Mihai Valentin , Chapon Patrick , Gaiaschi Sofia , Rokosz Krzysztof , Raaen Steinar , Motelica-Heino Mikael , Predoi Daniela
Published: April 2021

In this study, the cerium-doped hydroxyapatite (Ca10−xCex(PO4)6(OH)2 with xCe = 0.1, 10Ce-HAp) coatings obtained by the spin coating method were presented for the first time. The stability of the 10Ce-HAp suspension particles used in the preparation of coatings was evaluated by ultrasonic studies, transmission electron microscopy (TEM), X-ray diffraction (XRD), and scanning electron microscopy (SEM). The surface morphology of the 10Ce-HAp coating was studied by SEM and atomic force microscopy (AFM) techniques. The obtained 10Ce-HAp coatings were uniform and without cracks or unevenness. Glow discharge optical emission spectroscopy (GDOES) and X-ray photoelectron spectroscopy (XPS) were used for the investigation of fine chemical depth profiling. The antifungal properties of the HAp and 10Ce-HAp suspensions and coatings were assessed using Candida albicans ATCC 10231 (C. albicans) fungal strain. The quantitative antifungal assays demonstrated that both 10Ce-HAp suspensions and coatings exhibited strong antifungal properties and that they successfully inhibited the development and adherence of C. albicans fungal cells for all the tested time intervals. The scanning electron microscopy (SEM) and confocal laser scanning microscopy (CLSM) visualization of the C. albicans fungal cells adherence to the 10Ce-HAp surface also demonstrated their strong inhibitory effects. In addition, the qualitative assays also suggested that the 10Ce-HAp coatings successfully stopped the biofilm formation.
Fractional Power-Law Intraband Optical Conductivity in the Low-Dimensional Dirac Material CaMnBi2
Authors: Schilling M. B. , Wang C. X. , Shi Y. G. , Kremer R. K. , Dressel M. , Pronin A. V.
Published: April 2021

We studied the broadband optical conductivity of CaMnBi2, a material with two-dimensional Dirac electronic bands, and found that both components of the intraband conductivity follow a universal power law as a function of frequency at low temperatures. This conductivity scaling differs from the Drude(-like) behavior, generally expected for free carriers, but matches the predictions for the intraband response of an electronic system in a quantum critical region. Since no other indications of quantum criticality are reported for CaMnBi2 so far, the cause of the observed unusual scaling remains an open question.
Interfacial Bonding and Mechanical Properties of Al/Mg Dissimilar Refill Friction Stir Spot Welds Using a Grooved Tool
Authors: Shen Zhikang , Liu Xinyu , Li Dongxiao , Ding Yuquan , Hou Wentao , Chen Haiyan , Li Wenya , Gerlich Adrian P.
Published: April 2021

Al/Mg dissimilar welds were successfully fabricated by refill friction stir spot welding using a grooved sleeve tool. Influences of sleeve penetration depth and rotational speed on the weld formation and mechanical performance were systematically evaluated in terms of welding parameter optimization, interfacial bonding mechanism, hardness distribution and welded joint strength. The results indicated that the success of joining Al alloy to Mg alloy significantly depends on tool sleeve penetration depth. The interfacial bonding mechanism compromised both metallurgical bonding and mechanical inter-locking. Intermetallic compound layers of Al3Mg2 and Al12Mg17 were formed at the Al/Mg interface. The thickness of the intermetallic compound (IMC) layer at the weld center increased from 20–30 μm to 40 μm when the rotational speed increased from 1000 to 2000 rpm. The minimum hardness was 80 HV in Al 7075 and 52 HV in ZEK 100; both were measured in the heat affected zone. The welded joint lap shear strength decreased, and the scatter increased with the increasing of rotation speed, whose maximum was 3.6 kN when the rotational speed was 1000 rpm. In addition, the failure mechanism was determined by tool rotational speed, and found to be interfacial failure under a rotational speed of 1000 rpm and nugget pullout under a rotational speed of 2000 rpm.
The Prediction of the Undercooling Degree of As-Cast Irons and Aluminum Alloys via Machine Learning
Authors: Chen Yong , Wen Litao , Wang Shuncheng , Zhang Zhibo , Yin Cuicui , Zhou Nan , Zheng Kaihong
Published: April 2021

As-cast irons and aluminum alloys are used in various industrial fields and their phase and microstructure properties are strongly affected by the undercooling degree. However, existing studies regarding the undercooling degree are mostly limited to qualitative analyses. In this paper, a quantitative analysis of the undercooling degree is performed by collecting experimental data and employing machine learning. Nine machining learning models including Random Forest (RF), eXtreme Gradient Boosting (XGBOOST), Ridge Regression (RIDGE) and Gradient Boosting Regressor (GBDT) methods are used to predict the undercooling degree via six features, which include the cooling rate (CR), mean atomic covalence radius (MAR) and mismatch (MM). Four additional effective models of machine learning algorithms are then selected for a further analysis and cross-validation. Finally, the optimal machine learning model is selected for the dataset and the best combination of features is found by comparing the prediction accuracy of all possible feature combinations. It is found that RF model with CR and MAR features has the optimal performance results for predicting the undercooling degree.
Spatial Distribution of Lichens in Metrosideros excelsa in Northern New Zealand Urban Forests
Authors: Benitez Gladys N. , Aguilar Glenn D. , Blanchon Dan
Published: April 2021

The spatial distribution of corticolous lichens on the iconic New Zealand pōhutukawa (Metrosideros excelsa) tree was investigated from a survey of urban parks and forests across the city of Auckland in the North Island of New Zealand. Lichens were identified from ten randomly selected trees at 20 sampling sites, with 10 sites classified as coastal and another 10 as inland sites. Lichen data were correlated with distance from sea, distance from major roads, distance from native forests, mean tree DBH (diameter at breast height) and the seven-year average of measured NO2 over the area. A total of 33 lichen species were found with coastal sites harboring significantly higher average lichen species per tree as well as higher site species richness. We found mild hotspots in two sites for average lichen species per tree and another two separate sites for species richness, with all hotspots at the coast. A positive correlation between lichen species richness and DBH was found. Sites in coastal locations were more similar to each other in terms of lichen community composition than they were to adjacent inland sites and some species were only found at coastal sites. The average number of lichen species per tree was negatively correlated with distance from the coast, suggesting that the characteristic lichen flora found on pōhutukawa may be reliant on coastal microclimates. There were no correlations with distance from major roads, and a slight positive correlation between NO2 levels and average lichen species per tree.
Hypercoagulability as Measured by Thrombelastography May Be Associated with the Size of Acute Ischemic Infarct—A Pilot Study
Authors: Wiśniewski Adam , Karczmarska-Wódzka Aleksandra , Sikora Joanna , Sobczak Przemysław , Lemanowicz Adam , Filipska Karolina , Ślusarz Robert
Published: April 2021

Background: Thromboelastography (TEG®) measures coagulation function in venous blood. Previous studies have reported that this device providing an integrated data on dynamics of clot formation may be useful for predicting clinical outcome in ischemic stroke. We investigated whether a hypercoagulability detected by thrombelastography may be associated with larger size of acute ischemic infarct. Methods: We included 40 ischemic stroke subjects with large artery atherosclerosis or small-vessel disease to a cross-sectional pilot study. Thrombelastography parameters related to time of clot formation (R- reaction time, K-clot kinetics), clot growth and strengthening (angle-alpha and MA-maximum amplitude) and lysis (Ly30) were performed within first 24 h after the onset of stroke. A volume of ischemic infarct was assessed on the basis of diffusion-weighted imaging (DWI) sequence of magnetic resonance imaging. Results: In the entire group, we reported that subjects with a large ischemic focus (>2 cm3) had a higher diameter of a clot (measured as MA) than subjects with a small ischemic focus (p = 0.0168). In the large artery atherosclerosis subgroup, we showed a significant correlation between MA and size of acute infarct (R = 0.64, p = 0.0138), between angle (alpha) and size of acute infarct (R = 0.55, p = 0.0428) and stroke subjects with hypercoagulability (MA > 69 mm) had significantly higher probability of a larger size of acute ischemic focus compared to normalcoagulable subjects (5.45 cm3 vs. 1.35 cm3; p = 0.0298). In multivariate logistic regression hypercoagulability was a predictor of a large size of ischemic infarct (Odds ratio OR = 59.5; 95% confidence interval (CI) 1.08–3558.8; p = 0.0488). Conclusions: We emphasized that thrombelastography, based on the parameters related to clot strength, may have clinical utility to identify the risk of the extensive ischemic infarct.
An Emerging Anti-p16 Antibody-BC42 Clone as an Alternative to the Current E6H4 for Use in the Female Genital Tract Pathological Diagnosis: Our Experience and a Review on p16ink4a Functional Significance, Role in Daily-Practice Diagnosis, Prognostic Potential, and Technical Pitfalls
Authors: Angelico Giuseppe , Santoro Angela , Inzani Frediano , Straccia Patrizia , Spadola Saveria , Arciuolo Damiano , Valente Michele , D’Alessandris Nicoletta , Benvenuto Roberta , Travaglino Antonio , Raffone Antonio , Zannoni Gian Franco
Published: April 2021

Background: To date, useful diagnostic applications of p16 IHC have been documented in gynecological pathology both for HPV-related and non-HPV-related lesions. In the present article, we reported our experience with the novel anti-p16 INK4a antibody (clone BC42), whose expression was tested across all different gynecologic neoplasms; we also compared it to the traditional E6H4 clone. Moreover, we discussed and explored all the diagnostic applications of p16 IHC in gynecologic pathology. Methods: Consultation cases covering a 5-year period (2016–2020) regarding gynecological neoplastic and non-neoplastic lesions in which immunohistochemistry for p16, clone E6H4 was originally performed, were retrospectively retrieved from the files of our institution. Immunohistochemical staining for p16ink4a (BC42) [Biocare Medical group-Paceco USA; Bioptica Milan] and p16ink4a (E6H4) [Ventana Medical Systems-Arizona USA; Roche] was performed by using the Ventana automated immunostainer (Ventana Medical Systems, Tucson, AZ, USA). The immunostaining pattern was defined as negative, focal/patchy, or diffuse. Results: A total of 196 cases, represented by 36 high-grade SIL/CIN3 of the uterine cervix, 30 cervical adenocarcinomas, 22 cervical squamous cell carcinoma, 70 endometrial carcinomas, 25 high grade serous ovarian carcinomas, 6 uterine adenomatoid tumors, and 10 uterine leiomyosarcomas were included in this study. Results showed concordant staining quality of both clones on all tested neoplastic tissues. Conclusions: The novel anti-p16 antibody (BC42 clone) appeared as an alternative to the current E6H4 for use in gynecological neoplasms, offering similar levels of positivity and equally reliable staining results.
Pretreatment [18F]FDG PET/CT Prognostic Factors in Patients with Squamous Cell Cervical Carcinoma FIGO IIIC1
Authors: Burchardt Ewa , Burchardt Wojciech , Cegła Paulina , Kubiak Anna , Roszak Andrzej , Cholewiński Witold
Published: April 2021

Purpose: This study aims to determine whether semiquantitative parameters obtained from both the primary tumor and metastatic pelvic lymph nodes (PLN) diagnosed in fluoro-18-deoxy-glucose positron emission tomography (FDG-PET-CT) are associated with disease-free survival (DFS), local control (LC), distant metastasis-free survival (DMFS) and overall survival (OS) in patients with locally advanced squamous cervical cancer (LACC) and metastatic pelvic lymph nodes. Materials: Retrospective analysis was performed on 93 female patients with FIGO IIIC1. The median age was 53 years (27–75). The PET parameters both in the primary tumor and metastatic pelvic lymph nodes, including SUVmax, SUVmean, TLG, MTV, heterogeneity, along with clinical variables, before radical cisplatin-based radiochemotherapy (RCT) were analyzed. The p-values < 0.05 were considered statistically significant. Results: Median follow-up was 38 months (4.5–92.6). Three years and five years OS were 75% and 70% respectively. Patients with SUVmax above 12.6, SUVmean above 7.6 and with TLG in tumors >245.7 lived longer (p < 0.05). The higher SUVmax or SUVmean reduced increased DMFS (HR 0.3 95%CI 0.56–0.96 and 0.59 95%CI 0.37–0.93). The clinical factors and other FDG PET CT parameters were not found to be statistically relevant in terms of OS, DFS, DM and LC. Conclusions: This study is the first report showing that in LACC patient population with PLN involvement treated with definitive RCT, high SUVmean, SUVmax and TLG of the primary tumor in FDG-PET-CT were linked with longer OS. Lower SUVmean and SUVmax were linked with shorter DMFS. None of the clinical factors and the nodal FDG-PET-CT parameters influenced the outcome.
Empirical Mode Decomposition-Derived Entropy Features Are Beneficial to Distinguish Elderly People with a Falling History on a Force Plate Signal
Authors: Chou Li-Wei , Chang Kang-Ming , Wei Yi-Chun , Lu Mei-Kuei
Published: April 2021

Fall risk prediction is an important issue for the elderly. A center of pressure signal, derived from a force plate, is useful for the estimation of body calibration. However, it is still difficult to distinguish elderly people’s fall history by using a force plate signal. In this study, older adults with and without a history of falls were recruited to stand still for 60 s on a force plate. Forces in the x, y and z directions (Fx, Fy, and Fz) and center of pressure in the anteroposterior (COPx) and mediolateral directions (COPy) were derived. There were 49 subjects in the non-fall group, with an average age of 71.67 (standard derivation: 6.56). There were also 27 subjects in the fall group, with an average age of 70.66 (standard derivation: 6.38). Five signal series—forces in x, y, z (Fx, Fy, Fz), COPX, and COPy directions—were used. These five signals were further decomposed with empirical mode decomposition (EMD) with seven intrinsic mode functions. Time domain features (mean, standard derivation and coefficient of variations) and entropy features (approximate entropy and sample entropy) of the original signals and EMD-derived signals were extracted. Results showed that features extracted from the raw COP data did not differ significantly between the fall and non-fall groups. There were 10 features extracted using EMD, with significant differences observed among fall and non-fall groups. These included four features from COPx and two features from COPy, Fx and Fz.
Millimeter-Wave Metal Reflectarray Antennas with Sub-Wavelength Holes
Authors: Yi Minwoo , Bae Youngseok , Yoo Sungjun
Published: April 2021

Reflectarray antennas composed of rectangular grooves with sub-wavelength holes on a metal plate are designed for millimeter-wave regions. All depths of multiple grooves in the metal reflectarray are elaborately manipulated for a high-gain reflector. A sub-wavelength hole in each groove reduces the mass of the reflectarray antenna, which rarely affects the re-radiated millimeter-wave filed from the groove. In this paper, we have demonstrated light high-gain reflectarray antennas and achieved a 25%-light reflectarray antenna compared with a metal reflectarray without sub-wavelength holes. The designed reflectarray antenna operates within the 15% wide-band bandwidth at 3 dB for millimeter-wave band.
GPU-Based Embedded Intelligence Architectures and Applications
Authors: Ang Li Minn , Seng Kah Phooi
Published: April 2021

This paper present contributions to the state-of-the art for graphics processing unit (GPU-based) embedded intelligence (EI) research for architectures and applications. This paper gives a comprehensive review and representative studies of the emerging and current paradigms for GPU-based EI with the focus on the architecture, technologies and applications: (1) First, the overview and classifications of GPU-based EI research are presented to give the full spectrum in this area that also serves as a concise summary of the scope of the paper; (2) Second, various architecture technologies for GPU-based deep learning techniques and applications are discussed in detail; and (3) Third, various architecture technologies for machine learning techniques and applications are discussed. This paper aims to give useful insights for the research area and motivate researchers towards the development of GPU-based EI for practical deployment and applications.
Image Accessibility for Screen Reader Users: A Systematic Review and a Road Map
Authors: Oh Uran , Joh Hwayeon , Lee YunJung
Published: April 2021

A number of studies have been conducted to improve the accessibility of images using touchscreen devices for screen reader users. In this study, we conducted a systematic review of 33 papers to get a holistic understanding of existing approaches and to suggest a research road map given identified gaps. As a result, we identified types of images, visual information, input device and feedback modalities that were studied for improving image accessibility using touchscreen devices. Findings also revealed that there is little study how the generation of image-related information can be automated. Moreover, we confirmed that the involvement of screen reader users is mostly limited to evaluations, while input from target users during the design process is particularly important for the development of assistive technologies. Then we introduce two of our recent studies on the accessibility of artwork and comics, AccessArt and AccessComics, respectively. Based on the identified key challenges, we suggest a research agenda for improving image accessibility for screen reader users.
Efficient Stain-Aware Nuclei Segmentation Deep Learning Framework for Multi-Center Histopathological Images
Authors: Hassan Loay , Abdel-Nasser Mohamed , Saleh Adel , A. Omer Osama , Puig Domenec
Published: April 2021

Existing nuclei segmentation methods have obtained limited results with multi-center and multi-organ whole-slide images (WSIs) due to the use of different stains, scanners, overlapping, clumped nuclei, and the ambiguous boundary between adjacent cell nuclei. In an attempt to address these problems, we propose an efficient stain-aware nuclei segmentation method based on deep learning for multi-center WSIs. Unlike all related works that exploit a single-stain template from the dataset to normalize WSIs, we propose an efficient algorithm to select a set of stain templates based on stain clustering. Individual deep learning models are trained based on each stain template, and then, an aggregation function based on the Choquet integral is employed to combine the segmentation masks of the individual models. With a challenging multi-center multi-organ WSIs dataset, the experimental results demonstrate that the proposed method outperforms the state-of-art nuclei segmentation methods with aggregated Jaccard index (AJI) and F1-scores of 73.23% and 89.32%, respectively, while achieving a lower number of parameters.
Spatiotemporal Optimization for Short-Term Solar Forecasting Based on Satellite Imagery
Authors: Oh Myeongchan , Kim Chang Ki , Kim Boyoung , Yun Changyeol , Kang Yong-Heack , Kim Hyun-Goo
Published: April 2021

Solar forecasting is essential for optimizing the integration of solar photovoltaic energy into a power grid. This study presents solar forecasting models based on satellite imagery. The cloud motion vector (CMV) model is the most popular satellite-image-based solar forecasting model. However, it assumes constant cloud states, and its accuracy is, thus, influenced by changes in local weather characteristics. To overcome this limitation, satellite images are used to provide spatial data for a new spatiotemporal optimized model for solar forecasting. Four satellite-image-based solar forecasting models (a persistence model, CMV, and two proposed models that use clear-sky index change) are evaluated. The error distributions of the models and their spatial characteristics over the test area are analyzed. All models exhibited different performances according to the forecast horizon and location. Spatiotemporal optimization of the best model is then conducted using best-model maps, and our results show that the skill score of the optimized model is 21% better than the previous CMV model. It is, thus, considered to be appropriate for use in short-term forecasting over large areas. The results of this study are expected to promote the use of spatial data in solar forecasting models, which could improve their accuracy and provide various insights for the planning and operation of photovoltaic plants.