bluuebunny/crossref_metadata_2025 huggingface dataset:
Kynurenic Acid Electrochemical Immunosensor: Blood-Based Diagnosis of Alzheimer’s Disease
Authors: Marrugo-Ramírez Jose , Rodríguez-Núñez Montserrat , Marco M.-Pilar , Mir Mónica , Samitier Josep
Published: January 2021

Alzheimer’s disease (AD) is a neurodegenerative disorder, characterized by a functional deterioration of the brain. Currently, there are selected biomarkers for its diagnosis in cerebrospinal fluid. However, its extraction has several disadvantages for the patient. Therefore, there is an urgent need for a detection method using sensitive and selective blood-based biomarkers. Kynurenic acid (KYNA) is a potential biomarker candidate for this purpose. The alteration of the KYNA levels in blood has been related with inflammatory processes in the brain, produced as a protective function when neurons are damaged. This paper describes a novel electrochemical immunosensor for KYNA detection, based on successive functionalization multi-electrode array. The resultant sensor was characterized by cyclic voltammetry (CV), chronoamperometry (CA), and electrochemical impedance spectroscopy (EIS). The proposed biosensor detects KYNA within a linear calibration range from 10 pM to 100 nM using CA and EIS, obtaining a limit of detection (LOD) of 16.9 pM and 37.6 pM in buffer, respectively, being the lowest reported LOD for this biomarker. Moreover, to assess our device closer to the real application, the developed immunosensor was also tested under human serum matrix, obtaining an LOD of 391.71 pM for CA and 278.8 pM for EIS with diluted serum.
A R-Script for Generating Multiple Sclerosis Lesion Pattern Discrimination Plots
Authors: Marschallinger Robert , Tur Carmen , Marschallinger Hannes , Sellner Johann
Published: January 2021

One significant characteristic of Multiple Sclerosis (MS), a chronic inflammatory demyelinating disease of the central nervous system, is the evolution of highly variable patterns of white matter lesions. Based on geostatistical metrics, the MS-Lesion Pattern Discrimination Plot reduces complex three- and four-dimensional configurations of MS-White Matter Lesions to a well-arranged and standardized two-dimensional plot that facilitates follow-up, cross-sectional and medication impact analysis. Here, we present a script that generates the MS-Lesion Pattern Discrimination Plot, using the widespread statistical computing environment R. Input data to the script are Nifti-1 or Analyze-7.5 files with individual MS-White Matter Lesion masks in Montreal Normal Brain geometry. The MS-Lesion Pattern Discrimination Plot, variogram plots and associated fitting statistics are output to the R console and exported to standard graphics and text files. Besides reviewing relevant geostatistical basics and commenting on implementation details for smooth customization and extension, the paper guides through generating MS-Lesion Pattern Discrimination Plots using publicly available synthetic MS-Lesion patterns. The paper is accompanied by the R script LDPgenerator.r, a small sample data set and associated graphics for comparison.
Most Frequent Problems of Building Structures of Urban Apartment Buildings from 2nd Half of 19th Century and the Start of 20th Century
Authors: Kroftova Klara
Published: January 2021

An urban residential building from the second half of the 19th century and the start of the 20th century, the so-called tenement house, is a significant representative of the architecture of the developing urban fabric in Central Europe. The vertical and horizontal load-bearing structures of these houses currently tend to show characteristic, repeated defects and failures. Their knowledge may, in many cases, facilitate and speed up the design of the historic building’s restoration without compromising its heritage value in this process. The article presents the summary of the most frequently occurring defects and failures of these buildings. The summary, however, is not an absolute one, and, in the case of major damage to the building, it still applies that, first of all, a detailed analysis of the causes and consequences of defects and failures must be made as a basic prerequisite for the reliability and long-term durability of the building’s restoration and rehabilitation. An integral part of the rehabilitation of buildings must be the elimination of the causes of the appearance of their failures and remediation of all defects impairing their structural safety, health safety and energy efficiency.
Wilms’ Tumor 1 (WT1): A Novel Immunomarker of Dermatofibrosarcoma Protuberans—An Immunohistochemical Study on a Series of 114 Cases of Bland-Looking Mesenchymal Spindle Cell Lesions of the Dermis/Subcutaneous Tissues
Authors: Piombino Eliana , Broggi Giuseppe , Barbareschi Mattia , Castorina Sergio , Parenti Rosalba , Bartoloni Giovanni , Salvatorelli Lucia , Magro Gaetano
Published: January 2021

Purpose: to investigate the immunohistochemical expression and distribution of Wilms’ tumor 1 (WT1) (transcription factor produced by the tumor suppressor gene of the same name) in a series of 114 cases of bland-looking mesenchymal spindle cell lesions of the dermis/subcutaneous tissues to establish whether this immunomarker is differentially expressed in dermatofibrosarcoma protuberans (DFSP) versus its potential morphological mimickers. Methods: This retrospective multi-centric immunohistochemical study included 57 DFSP cases, 15 dermatofibromas, 5 deep fibrous histiocytomas, 8 neurofibromas, 5 spindle cell lipomas, 8 dermal scars, 6 nodular fasciitis, 5 cutaneous leiomyomas and 5 solitary fibrous tumors. Among the 57 DFSP cases, 11 were recurrent lesions; 2 non-recurrent cases exhibited an additional “fibrosarcomatous” overgrowth and 1 recurrent and 2 primary tumors contained a minority of “giant cell fibroblastoma” components. Results: Most DFSP (95% of cases) exhibited cytoplasmic staining for WT1; 11/11 residual/recurrent tumors showed diffuse and strong WT1 cytoplasmic immunoreactivity; apart from neurofibromas, WT1 expression was lacking in all the other cases studied. Conclusions: The cytoplasmic expression of WT1 may be exploitable as a complementary diagnostic immunomarker to CD34 in confirming the diagnosis of DFSP and to better evaluate the residual/recurrent tumor component.
Use of Antiangiogenic Therapies in Pediatric Solid Tumors
Authors: Ollauri-Ibáñez Claudia , Astigarraga Itziar
Published: January 2021

Cancer is an important cause of death in childhood. In recent years, scientists have made an important effort to achieve greater precision and more personalized treatments against cancer. But since only a few pediatric patients have identifiable therapeutic targets, other ways to stop the neoplastic cell proliferation and dissemination are needed. Therefore, the inhibition of general processes involved in the growth and behavior of tumors can be a relevant strategy for the development of new cancer therapies. In the case of solid tumors, one of these processes is angiogenesis, essential for tumor growth and generation of metastases. This review summarizes the results obtained with the use of antiangiogenic drugs in the main pediatric malignant solid tumors and also an overview of clinical trials currently underway. It should be noted that due to the rarity and heterogeneity of the different types of pediatric cancer, most studies on antiangiogenic drugs include only a small number of patients or isolated clinical cases, so they are not conclusive and further studies are needed.
Homologous Recombination Repair Mechanisms in Serous Endometrial Cancer
Authors: Jönsson Jenny-Maria , Bååth Maria , Björnheden Ida , Sahin Irem Durmaz , Måsbäck Anna , Hedenfalk Ingrid
Published: January 2021

Serous endometrial cancer (SEC) resembles high-grade serous ovarian cancer (HGSOC) genetically and clinically, with recurrent copy number alterations, TP53 mutations and a poor prognosis. Thus, SEC patients may benefit from targeted treatments used in HGSOC, e.g., PARP inhibitors. However, the preclinical and clinical knowledge about SEC is scarce, and the exact role of defective DNA repair in this tumor subgroup is largely unknown. We aimed to outline the prevalence of homologous recombination repair deficiency (HRD), copy-number alterations, and somatic mutations in SEC. OncoScan SNP arrays were applied to 19 tumors in a consecutive SEC series to calculate HRD scores and explore global copy-number profiles and genomic aberrations. Copy-number signatures were established and targeted sequencing of 27 HRD-associated genes was performed. All factors were examined in relation to HRD scores to investigate potential drivers of the HRD phenotype. Ten of the 19 SEC tumors (53%) had an HRD score > 42, considered to reflect an HRD phenotype. Higher HRD score was associated with loss of heterozygosity in key HRD genes, and copy-number signatures associated with non-BRCA1/2 dependent HRD in HGSOC. A high number of SECs display an HRD phenotype. It remains to be elucidated whether this also confers PARP inhibitor sensitivity.
Enhanced Expression of miR-181b in B Cells of CLL Improves the Anti-Tumor Cytotoxic T Cell Response
Authors: Di Marco Mirco , Veschi Serena , Lanuti Paola , Ramassone Alice , Pacillo Stefania , Pagotto Sara , Pepe Felice , George-William Jonahunnatha Nesson , Curcio Claudia , Marchisio Marco , Miscia Sebastiano , Innocenti Idanna , Autore Francesco , Vannata Barbara , Di Gregorio Patrizia , Di Gioacchino Mario , Valentinuzzi Silvia , Iezzi Manuela , Mariani-Costantini Renato , Larocca Luigi Maria , Laurenti Luca , Veronese Angelo , Visone Rosa
Published: January 2021

The clinical progression of B cell chronic lymphocytic leukemia (CLL) is associated with immune cell dysfunction and a strong decrease of miR-181b-5p (miR-181b), promoting the death of CLL cells. Here we investigated whether the reduction of miR-181b impairs the immune response in CLL. We demonstrate that activated CD4+ T cells increase miR-181b expression in CLL through CD40–CD40L signaling, which enhances the maturation and activity of cytotoxic T cells and, consequently, the apoptotic response of CLL cells. The cytotoxic response is facilitated by a depletion of the anti-inflammatory cytokine interleukin 10, targeted by miR-181b. In vivo experiments in NOD.Cg-Prkdcscid Il2rgtm1Wjl/SzJ mice confirmed that miR-181b promotes the apoptotic death of CLL cells only when functional T cells are restored. Overall, our findings suggest that the reinstatement of miR-181b in CLL cells could be an exploitable adjuvant therapeutic option for the treatment of CLL.
Immunotherapeutic Efficacy of Retargeted oHSVs Designed for Propagation in an Ad Hoc Cell Line
Authors: Vannini Andrea , Leoni Valerio , Sanapo Mara , Gianni Tatiana , Giordani Giorgia , Gatta Valentina , Barboni Catia , Zaghini Anna , Campadelli-Fiume Gabriella
Published: January 2021

Our laboratory has pursued the generation of cancer-specific oncolytic herpes simplex viruses (oHSVs) which ensure high efficacy while maintaining a high safety profile. Their blueprint included retargeting to a Tumor-Associated Antigen, e.g., HER2, coupled to detargeting from natural receptors to avoid off-target and off-tumor infections and preservation of the full complement of unmodified viral genes. These oHSVs are “fully virulent in their target cancer cells”. The 3rd generation retargeted oHSVs carry two distinct retargeting moieties, which enable infection of a producer cell line and of the target cancer cells, respectively. They can be propagated in an ad hoc Vero cell derivative at about tenfold higher yields than 1st generation recombinants, and more effectively replicate in human cancer cell lines. The R-335 and R-337 prototypes were armed with murine IL-12. Intratumorally-administered R-337 conferred almost complete protection from LLC-1-HER2 primary tumors, unleashed the tumor microenvironment immunosuppression, synergized with the checkpoint blockade and conferred long-term vaccination against distant challenge tumors. In summary, the problem intrinsic to the propagation of retargeted oHSVs—which strictly require cells positive for targeted receptors—was solved in 3rd generation viruses. They are effective as immunotherapeutic agents against primary tumors and as antigen-agnostic vaccines.
Towards Green, Enhanced Photocatalysts for Hydrogen Evolution
Authors: Profumo Antonella , Speltini Andrea
Published: January 2021

The constant growth of energy demand joined with the adverse effects on the global environment induced by use of fossil fuels is increasingly requiring new routes to obtain clean and renewable energy sources [...]
The Application of Copper-Gold Catalysts in the Selective Oxidation of Glycerol at Acid and Basic Conditions
Authors: Kaminski Piotr
Published: January 2021

The crude glycerol is produced during the transesterification of animal fats and vegetable oils, but it is a by-product of this process. Currently, its elimination is a problem in the chemical industry. The main goal of this work was the preparation, characterization and application of mesoporous cerium-zirconium oxide as supports for copper and gold species and the comparison of selected factors on the properties of catalysts in glycerol oxidation in the liquid phase. The samples were characterized using adsorption and desorption of nitrogen, XRD, UV-vis, XPS, TEM, SEM, and STEM-EDXS. The obtained results of glycerol oxidation show that the bimetallic copper-gold catalysts are more active and selective to glyceric acid in this reaction than analogous monometallic gold catalysts. Additionally, bimetallic catalysts are also characterized by the catalytic stability, and their application leads to the increase of selectivity to glyceric acid during their reusing in glycerol oxidation in alkali media. In this work, the influence of selected factors, e.g., oxygen source and its pressure, solution pH, and base content on the catalytic activity of bimetallic catalysts is discussed.
Acidity as Descriptor for Methanol Desorption in B-, Ga- and Ti-MFI Zeotypes
Authors: Creci Simone , Martinelli Anna , Vavra Szilvia , Carlsson Per-Anders , Skoglundh Magnus
Published: January 2021

The isomorphous substitution of Si with metals other than Al in zeotype frameworks allows for tuning the acidity of the zeotype and, therefore, to tailor the catalyst’s properties as a function of the desired catalytic reaction. In this study, B, Ga, and Ti are incorporated in the MFI framework of silicalite samples and the following series of increasing acidity is observed: Ti-silicalite < B-silicalite < Ga-silicalite. It is also observed that the lower the acidity of the sample, the easier the methanol desorption from the zeotype surface. In the target reaction, namely the direct conversion of methane to methanol, methanol extraction is affected by the zeotype acidity. Therefore, the results shown in this study contribute to a more enriched knowledge of this reaction.
Energetic Characterization of Faujasite Zeolites Using a Sensor Gas Calorimeter
Authors: Mauer Volker , Bläker Christian , Pasel Christoph , Bathen Dieter
Published: January 2021

In addition to the adsorption mechanism, the heat released during exothermic adsorption influences the chemical reactions that follow during heterogeneous catalysis. Both steps depend on the structure and surface chemistry of the catalyst. An example of a typical catalyst is the faujasite zeolite. For faujasite zeolites, the influence of the Si/Al ratio and the number of Na+ and Ca2+ cations on the heat of adsorption was therefore investigated in a systematic study. A comparison between a NaX (Sodium type X faujasite) and a NaY (Sodium type Y faujasite) zeolite reveals that a higher Si/Al ratio and therefore a smaller number of the cations in faujasite zeolites leads to lower loadings and heats. The exchange of Na+ cations for Ca2+ cations also has an influence on the adsorption process. Loadings and heats first decrease slightly at a low degree of exchange and increase significantly with higher calcium contents. If stronger interactions are required for heterogeneous catalysis, then the CaNaX zeolites must have a degree of exchange above 53%. The energetic contributions show that the highest-quality adsorption sites III and III’ make a contribution to the load-dependent heat of adsorption, which is about 1.4 times (site III) and about 1.8 times (site III’) larger than that of adsorption site II.
Ligands and Receptors Involved in the Sperm-Zona Pellucida Interactions in Mammals
Authors: Tumova Lucie , Zigo Michal , Sutovsky Peter , Sedmikova Marketa , Postlerova Pavla
Published: January 2021

Sperm-zona pellucida (ZP) interaction, involving the binding of sperm surface ligands to complementary carbohydrates of ZP, is the first direct gamete contact event crucial for subsequent gamete fusion and successful fertilization in mammals. It is a complex process mediated by the coordinated engagement of multiple ZP receptors forming high-molecular-weight (HMW) protein complexes at the acrosomal region of the sperm surface. The present article aims to review the current understanding of sperm-ZP binding in the four most studied mammalian models, i.e., murine, porcine, bovine, and human, and summarizes the candidate ZP receptors with established ZP affinity, including their origins and the mechanisms of ZP binding. Further, it compares and contrasts the ZP structure and carbohydrate composition in the aforementioned model organisms. The comprehensive understanding of sperm-ZP interaction mechanisms is critical for the diagnosis of infertility and thus becomes an integral part of assisted reproductive therapies/technologies.
Double Duty: Mitotic Kinesins and Their Post-Mitotic Functions in Neurons
Authors: Joseph Nadine F. , Swarnkar Supriya , Puthanveettil Sathyanarayanan V
Published: January 2021

Neurons, regarded as post-mitotic cells, are characterized by their extensive dendritic and axonal arborization. This unique architecture imposes challenges to how to supply materials required at distal neuronal components. Kinesins are molecular motor proteins that mediate the active delivery of cellular materials along the microtubule cytoskeleton for facilitating the local biochemical and structural changes at the synapse. Recent studies have made intriguing observations that some kinesins that function during neuronal mitosis also have a critical role in post-mitotic neurons. However, we know very little about the function and regulation of such kinesins. Here, we summarize the known cellular and biochemical functions of mitotic kinesins in post-mitotic neurons.
Seeding Propensity and Characteristics of Pathogenic αSyn Assemblies in Formalin-Fixed Human Tissue from the Enteric Nervous System, Olfactory Bulb, and Brainstem in Cases Staged for Parkinson’s Disease
Authors: Fenyi Alexis , Duyckaerts Charles , Bousset Luc , Braak Heiko , Del Tredici Kelly , Melki Ronald ,   on behalf of the Brainbank Neuro-CEB Neuropathology Network
Published: January 2021

We investigated α-synuclein’s (αSyn) seeding activity in tissue from the brain and enteric nervous system. Specifically, we assessed the seeding propensity of pathogenic αSyn in formalin-fixed tissue from the gastric cardia and five brain regions of 29 individuals (12 Parkinson’s disease, 8 incidental Lewy body disease, 9 controls) using a protein misfolding cyclic amplification assay. The structural characteristics of the resultant αSyn assemblies were determined by limited proteolysis and transmission electron microscopy. We show that fixed tissue from Parkinson’s disease (PD) and incidental Lewy body disease (ILBD) seeds the aggregation of monomeric αSyn into fibrillar assemblies. Significant variations in the characteristics of fibrillar assemblies derived from different regions even within the same individual were observed. This finding suggests that fixation stabilizes seeds with an otherwise limited seeding propensity, that yield assemblies with different intrinsic structures (i.e., strains). The lag phase preceding fibril assembly for patients ≥80 was significantly shorter than in other age groups, suggesting the existence of increased numbers of seeds or a higher seeding potential of pathogenic αSyn with time. Seeding activity did not diminish in late-stage disease. No statistically significant difference in the seeding efficiency of specific regions was found, nor was there a relationship between seeding efficiency and the load of pathogenic αSyn in a particular region at a given neuropathological stage.
Mimicking Tumor Hypoxia in Non-Small Cell Lung Cancer Employing Three-Dimensional In Vitro Models
Authors: Ziółkowska-Suchanek Iwona
Published: January 2021

Hypoxia is the most common microenvironment feature of lung cancer tumors, which affects cancer progression, metastasis and metabolism. Oxygen induces both proteomic and genomic changes within tumor cells, which cause many alternations in the tumor microenvironment (TME). This review defines current knowledge in the field of tumor hypoxia in non-small cell lung cancer (NSCLC), including biology, biomarkers, in vitro and in vivo studies and also hypoxia imaging and detection. While classic two-dimensional (2D) in vitro research models reveal some hypoxia dependent manifestations, three-dimensional (3D) cell culture models more accurately replicate the hypoxic TME. In this study, a systematic review of the current NSCLC 3D models that have been able to mimic the hypoxic TME is presented. The multicellular tumor spheroid, organoids, scaffolds, microfluidic devices and 3D bioprinting currently being utilized in NSCLC hypoxia studies are reviewed. Additionally, the utilization of 3D in vitro models for exploring biological and therapeutic parameters in the future is described.
The WNT/ROR Pathway in Cancer: From Signaling to Therapeutic Intervention
Authors: Menck Kerstin , Heinrichs Saskia , Baden Cornelia , Bleckmann Annalen
Published: January 2021

The WNT pathway is one of the major signaling cascades frequently deregulated in human cancer. While research had initially focused on signal transduction centered on β-catenin as a key effector activating a pro-tumorigenic transcriptional response, nowadays it is known that WNT ligands can also induce a multitude of β-catenin-independent cellular pathways. Traditionally, these comprise WNT/planar cell polarity (PCP) and WNT/Ca2+ signaling. In addition, signaling via the receptor tyrosine kinase-like orphan receptors (RORs) has gained increasing attention in cancer research due to their overexpression in a multitude of tumor entities. Active WNT/ROR signaling has been linked to processes driving tumor development and progression, such as cell proliferation, survival, invasion, or therapy resistance. In adult tissue, the RORs are largely absent, which has spiked the interest in them for targeted cancer therapy. Promising results in preclinical and initial clinical studies are beginning to unravel the great potential of such treatment approaches. In this review, we summarize seminal findings on the structure and expression of the RORs in cancer, their downstream signaling, and its output in regard to tumor cell function. Furthermore, we present the current clinical anti-ROR treatment strategies and discuss the state-of-the-art, as well as the challenges of the different approaches.
Exercise Ameliorates Spinal Cord Injury by Changing DNA Methylation
Authors: Davaa Ganchimeg , Hong Jin Young , Kim Tae Uk , Lee Seong Jae , Kim Seo Young , Hong Kwonho , Hyun Jung Keun
Published: January 2021

Exercise training is a traditional method to maximize remaining function in patients with spinal cord injury (SCI), but the exact mechanism by which exercise promotes recovery after SCI has not been identified; whether exercise truly has a beneficial effect on SCI also remains unclear. Previously, we showed that epigenetic changes in the brain motor cortex occur after SCI and that a treatment leading to epigenetic modulation effectively promotes functional recovery after SCI. We aimed to determine how exercise induces functional improvement in rats subjected to SCI and whether epigenetic changes are engaged in the effects of exercise. A spinal cord contusion model was established in rats, which were then subjected to treadmill exercise for 12 weeks. We found that the size of the lesion cavity and the number of macrophages were decreased more in the exercise group than in the control group after 12 weeks of injury. Immunofluorescence and DNA dot blot analysis revealed that levels of 5-methylcytosine (5mC) and 5-hydroxymethylcytosine (5hmC) in the brain motor cortex were increased after exercise. Accordingly, the expression of ten-eleven translocation (Tet) family members (Tet1, Tet2, and Tet3) in the brain motor cortex also elevated. However, no macrophage polarization was induced by exercise. Locomotor function, including Basso, Beattie, and Bresnahan (BBB) and ladder scores, also improved in the exercise group compared to the control group. We concluded that treadmill exercise facilitates functional recovery in rats with SCI, and mechanistically epigenetic changes in the brain motor cortex may contribute to exercise-induced improvements.
The Inhibition of CDK8/19 Mediator Kinases Prevents the Development of Resistance to EGFR-Targeting Drugs
Authors: Sharko Amanda C. , Lim Chang-Uk , McDermott Martina S. J. , Hennes Chuck , Philavong Kingsavanh P. , Aiken Tiffanie , Tatarskiy Victor V. , Roninson Igor B. , Broude Eugenia V.
Published: January 2021

Drug resistance is the main obstacle to achieving cures with both conventional and targeted anticancer drugs. The emergence of acquired drug resistance is initially mediated by non-genetic transcriptional changes, which occur at a much higher frequency than mutations and may involve population-scale transcriptomic adaptation. CDK8/19 kinases, through association with transcriptional Mediator complex, regulate transcriptional reprogramming by co-operating with different signal-responsive transcription factors. Here we tested if CDK8/19 inhibition could prevent adaptation to drugs acting on epidermal growth factor receptor (EGFR/ERBB1/HER1). The development of resistance was analyzed following long-term exposure of BT474 and SKBR3 breast cancer cells to EGFR-targeting small molecules (gefitinib, erlotinib) and of SW48 colon cancer cells to an anti-EGFR monoclonal antibody cetuximab. In all cases, treatment of small cell populations (~105 cells) with a single dose of the drug initially led to growth inhibition that was followed by the resumption of proliferation and development of drug resistance in the adapted populations. However, this adaptation was always prevented by the addition of selective CDK8/19 inhibitors, even though such inhibitors alone had only moderate or no effect on cell growth. These results indicate that combining EGFR-targeting drugs with CDK8/19 inhibitors may delay or prevent the development of tumor resistance to therapy.
Lessons Learned from a Collaborative to Develop a Sustainable Simulation-Based Training Program in Neonatal Resuscitation: Simulating Success
Authors: Arul Nandini , Ahmad Irfan , Hamilton Justin , Sey Rachelle , Tillson Patricia , Hutson Shandee , Narang Radhika , Norgaard Jennifer , Lee Henry C. , Bergin Janine , Quinn Jenny , Halamek Louis P. , Yamada Nicole K. , Fuerch Janene , Chitkara Ritu
Published: January 2021

Newborn resuscitation requires a multidisciplinary team effort to deliver safe, effective and efficient care. California Perinatal Quality Care Collaborative’s Simulating Success program was designed to help hospitals implement on-site simulation-based neonatal resuscitation training programs. Partnering with the Center for Advanced Pediatric and Perinatal Education at Stanford, Simulating Success engaged hospitals over a 15 month period, including three months of preparatory training and 12 months of implementation. The experience of the first cohort (Children’s Hospital of Orange County (CHOC), Sharp Mary Birch Hospital for Women and Newborns (SMB) and Valley Children’s Hospital (VCH)), with their site-specific needs and aims, showed that a multidisciplinary approach with a sound understanding of simulation methodology can lead to a dynamic simulation program. All sites increased staff participation. CHOC reduced latent safety threats measured during team exercises from 4.5 to two per simulation while improving debriefing skills. SMB achieved 100% staff participation by identifying unit-specific hurdles within in situ simulation. VCH improved staff confidence level in responding to neonatal codes and proved feasibility of expanding simulation across their hospital system. A multidisciplinary approach to quality improvement in neonatal resuscitation fosters engagement, enables focus on patient safety rather than individual performance, and leads to identification of system issues.
Three-Dimensional Presentation of Tumor Histopathology: A Model Using Tongue Squamous Cell Carcinoma
Authors: Koivuholma Anne , Aro Katri , Mäkitie Antti , Salmi Mika , Mirtti Tuomas , Hagström Jaana , Atula Timo
Published: January 2021

Medical imaging often presents objects in three-dimensional (3D) form to provide better visual understanding. In contrast, histopathology is typically presented as two-dimensional (2D). Our objective was to present the tumor dimensions in 3D by creating a 3D digital model of it and so demonstrate the location of the tumor and the histological slices within the surgical soft tissue resection specimen. We developed a novel method for modeling a tongue squamous cell carcinoma using commonly available instruments. We established our 3D-modeling method by recognizing and solving challenges that concern the selection of the direction of histological slices. Additional steps to standard handling included scanning the specimen prior to grossing and modeling the carcinoma, which required only a table scanner and modeling software. We present challenges and their solutions in modeling the resection specimen and its histological slices. We introduce a finished 3D model of a soft tissue resection specimen and the actual tumor as well as its histopathological grossing sites in 3D digital and printed form. Our novel method provides steps to create a digital model of soft tissue resection specimen and the tumor within. To our knowledge, this is the first attempt to present histopathological margins of a tongue tumor in 3D form, whereas previously, only 2D has been available. The creation of the 3D model does not call for predetermined grossing directions for the pathologist. In addition, it provides a crucial initiative to enhance oncological management. The method allows a better visual understanding of tumor margins, topography, and orientation. It thus provides a tool for an improved postoperative assessment and aids, for example, in the discussion of the need for additional surgery and adjuvant therapy.
New Trends in Vascular Imaging
Authors: Hansen Kristoffer Lindskov , Carlsen Jonathan Frederik
Published: January 2021

Blood flow is essential to life and intertwined with all processes in the human body [...]
Towards Automated Eye Diagnosis: An Improved Retinal Vessel Segmentation Framework Using Ensemble Block Matching 3D Filter
Authors: Naveed Khuram , Abdullah Faizan , Madni Hussain Ahmad , Khan Mohammad A.U. , Khan Tariq M. , Naqvi Syed Saud
Published: January 2021

Automated detection of vision threatening eye disease based on high resolution retinal fundus images requires accurate segmentation of the blood vessels. In this regard, detection and segmentation of finer vessels, which are obscured by a considerable degree of noise and poor illumination, is particularly challenging. These noises include (systematic) additive noise and multiplicative (speckle) noise, which arise due to various practical limitations of the fundus imaging systems. To address this inherent issue, we present an efficient unsupervised vessel segmentation strategy as a step towards accurate classification of eye diseases from the noisy fundus images. To that end, an ensemble block matching 3D (BM3D) speckle filter is proposed for removal of unwanted noise leading to improved detection. The BM3D-speckle filter, despite its ability to recover finer details (i.e., vessels in fundus images), yields a pattern of checkerboard artifacts in the aftermath of multiplicative (speckle) noise removal. These artifacts are generally ignored in the case of satellite images; however, in the case of fundus images, these artifacts have a degenerating effect on the segmentation or detection of fine vessels. To counter that, an ensemble of BM3D-speckle filter is proposed to suppress these artifacts while further sharpening the recovered vessels. This is subsequently used to devise an improved unsupervised segmentation strategy that can detect fine vessels even in the presence of dominant noise and yields an overall much improved accuracy. Testing was carried out on three publicly available databases namely Structured Analysis of the Retina (STARE), Digital Retinal Images for Vessel Extraction (DRIVE) and CHASE_DB1. We have achieved a sensitivity of 82.88, 81.41 and 82.03 on DRIVE, SATARE, and CHASE_DB1, respectively. The accuracy is also boosted to 95.41, 95.70 and 95.61 on DRIVE, SATARE, and CHASE_DB1, respectively. The performance of the proposed methods on images with pathologies was observed to be more convincing than the performance of similar state-of-the-art methods.
The Effects of Toothbrush Wear on the Surface Roughness and Gloss of Resin Composites with Various Types of Matrices
Authors: AlAli Murtadha , Silikas Nikolaos , Satterthwaite Julian
Published: January 2021

Objective: To evaluate and compare the surface roughness and gloss of a DMA-free composite and Bis-GMA-free composite with a DMA-based composite before and after toothbrushing simulation. Materials and Methods: Fifteen dimensionally standardised composite specimens of three nano-hybrid resin composites (Tetric EvoCeram, Admira Fusion, and Venus Diamond) were used. Five specimens from each composite were polished and then subjected to a toothbrushing simulator. Surface roughness (Ra) and gloss were measured before toothbrushing and after 5000, 10,000, 15,000, and 20,000 toothbrushing cycles. The data was analysed using 5 × 3 ANOVA to assess surface roughness and gloss values and pairwise comparisons in the form of Tukey post hoc tests were performed to interpret main effects. Results: For all tested materials, surface roughness increased, and gloss decreased after toothbrushing abrasion. Surface roughness (Ra) values ranged from 0.14 to 0.22 μm at baseline and increased to between 0.41 and 0.49 μm after 20,000 toothbrushing cycles. Gloss values ranged between 31.9 and 50.6 GU at baseline and between 5.1 and 19.5 GU after 20,000 toothbrushing cycles. The lowest initial Ra value was detected in Venus Diamond and the highest initial gloss value was detected in Tetric EvoCeram. Conclusions: Simulated toothbrushing abrasion led to an increase in surface roughness and a decrease in gloss for all tested materials. Venus Diamond had the smoothest surface and Tetric EvoCeram had the glossiest surface after polishing and following 20,000 cycles of toothbrushing abrasion. Admira Fusion demonstrated the roughest surface and had the lowest gloss values before and after toothbrushing abrasion.
High-Entropy Alloys for Advanced Nuclear Applications
Authors: Pickering Ed J. , Carruthers Alexander W. , Barron Paul J. , Middleburgh Simon C. , Armstrong David E. J. , Gandy Amy S.
Published: January 2021

The expanded compositional freedom afforded by high-entropy alloys (HEAs) represents a unique opportunity for the design of alloys for advanced nuclear applications, in particular for applications where current engineering alloys fall short. This review assesses the work done to date in the field of HEAs for nuclear applications, provides critical insight into the conclusions drawn, and highlights possibilities and challenges for future study. It is found that our understanding of the irradiation responses of HEAs remains in its infancy, and much work is needed in order for our knowledge of any single HEA system to match our understanding of conventional alloys such as austenitic steels. A number of studies have suggested that HEAs possess ‘special’ irradiation damage resistance, although some of the proposed mechanisms, such as those based on sluggish diffusion and lattice distortion, remain somewhat unconvincing (certainly in terms of being universally applicable to all HEAs). Nevertheless, there may be some mechanisms and effects that are uniquely different in HEAs when compared to more conventional alloys, such as the effect that their poor thermal conductivities have on the displacement cascade. Furthermore, the opportunity to tune the compositions of HEAs over a large range to optimise particular irradiation responses could be very powerful, even if the design process remains challenging.
Distribution-Dependent Weighted Union Bound
Authors: Oneto Luca , Ridella Sandro
Published: January 2021

In this paper, we deal with the classical Statistical Learning Theory’s problem of bounding, with high probability, the true risk R(h) of a hypothesis h chosen from a set H of m hypotheses. The Union Bound (UB) allows one to state that PLR^(h),δqh≤R(h)≤UR^(h),δph≥1−δ where R^(h) is the empirical errors, if it is possible to prove that P{R(h)≥L(R^(h),δ)}≥1−δ and P{R(h)≤U(R^(h),δ)}≥1−δ, when h, qh, and ph are chosen before seeing the data such that qh,ph∈[0,1] and ∑h∈H(qh+ph)=1. If no a priori information is available qh and ph are set to 12m, namely equally distributed. This approach gives poor results since, as a matter of fact, a learning procedure targets just particular hypotheses, namely hypotheses with small empirical error, disregarding the others. In this work we set the qh and ph in a distribution-dependent way increasing the probability of being chosen to function with small true risk. We will call this proposal Distribution-Dependent Weighted UB (DDWUB) and we will retrieve the sufficient conditions on the choice of qh and ph that state that DDWUB outperforms or, in the worst case, degenerates into UB. Furthermore, theoretical and numerical results will show the applicability, the validity, and the potentiality of DDWUB.
Skills for a Working Future: How to Bring about Professional Success from the Educational Setting
Authors: García-Pérez Laura , García-Garnica Marina , Olmedo-Moreno Eva María
Published: January 2021

Globalization, digitalization, and the permanent alteration of information have led to important changes in the world of work. This demands a realignment of essential skills in order to access job positions in the coming years. In order to face up to the digitalization process, education is one of the ambits that has most come to a tipping point. This adds an urgency to the need to bring skills in line with the new demands of the job market and the challenges posed in the 21st Century. The methodology was based on a systematic review of the most commonly-used databases. It analyzed and synthesized the existing information on the skills required for the future job market and educational proposals to facilitate their acquisition. At the beginning of the search, 2045 records were selected. However, following the application of the exclusion criteria, a total of 63 records were included. From this in-depth analysis, it was uncovered that the most in-demand skill for the job market relates to the management of technology. Different proposals were located which targeted these skills in educational settings. The majority of these pertained to innovative projects emanating from digital and technological phenomena.
Internet of Things (IoT)-Based Wireless Health: Enabling Technologies and Applications
Authors: Islam S. M. Riazul , Lloret Jaime , Zikria Yousaf Bin
Published: January 2021

Wireless health is transforming health care by integrating wireless technologies into conventional medicine, including the diagnosis, monitoring, and treatment of illness [...]
Integrated Management Strategy with Feasible Smartness over Heterogeneous IoT Environments
Authors: Yang Taehun , Han Jinsoo
Published: January 2021

Recently, Internet of Things (IoT) applications have been increasingly deployed in smart domains, such as homes, buildings, and so on. A wide variety of smart devices and solutions bring improved lifestyles. However, current provider-oriented and individual application deployment leads to the separation of a smart domain into respective regions by providers and applications. Such heterogeneous environments hinder unified operation and the utilization of smart IoT applications. Therefore, this Article firstly addresses analyses on conventional smart domain technologies—smart home, smart building, etc.— and deployment in the real world with heterogeneous IoT technologies; then, a novel smart domain strategy for inter-cloud and inter-service operability and mobile-user-attached interactivity is proposed. Performance is compared in terms of user experience and service availability. Finally, numeric analyses are provided to prove the proposed strategy, and the proof-of-concept is presented to show feasibility and performances.
Hybrid High-Order and Fractional-Order Total Variation with Nonlocal Regularization for Compressive Sensing Image Reconstruction
Authors: Hou Lijia , Qin Yali , Zheng Huan , Pan Zemin , Mei Jicai , Hu Yingtian
Published: January 2021

Total variation often yields staircase artifacts in the smooth region of the image reconstruction. This paper proposes a hybrid high-order and fractional-order total variation with nonlocal regularization algorithm. The nonlocal means regularization is introduced to describe image structural prior information. By selecting appropriate weights in the fractional-order and high-order total variation coefficients, the proposed algorithm makes the fractional-order and the high-order total variation complement each other on image reconstruction. It can solve the problem of non-smooth in smooth areas when fractional-order total variation can enhance image edges and textures. In addition, it also addresses high-order total variation alleviates the staircase artifact produced by traditional total variation, still smooth the details of the image and the effect is not ideal. Meanwhile, the proposed algorithm suppresses painting-like effects caused by nonlocal means regularization. The Lagrange multiplier method and the alternating direction multipliers method are used to solve the regularization problem. By comparing with several state-of-the-art reconstruction algorithms, the proposed algorithm is more efficient. It does not only yield higher peak-signal-to-noise ratio (PSNR) and structural similarity (SSIM) but also retain abundant details and textures efficiently. When the measurement rate is 0.1, the gains of PSNR and SSIM are up to 1.896 dB and 0.048 dB respectively compared with total variation with nonlocal regularization (TV-NLR).
A Design Method of Compensation Circuit for High-Power Dynamic Capacitive Power Transfer System Considering Coupler Voltage Distribution for Railway Applications
Authors: Liang Jianying , Wu Donghua , Yu Jin
Published: January 2021

Capacitive power transfer (CPT) is a promising method to solve the problems caused by the traditional Pantograph-catenary contact power supply for railway applications. In contrast, the CPT system suffers a broken risk because of the small coupling capacitor. This paper has analyzed the CPT coupler’s voltage distributions for dynamic CPT systems when high power is required in real railway applications. The triangle relationship among the coupler voltages is derived. The circuit of the CPT system to accolated the coupler voltage is analyzed. Then, the compensation parameters are given. With the adopted LCLC-CL topology, the design process is presented by considering the coupler voltages. An experimental setup is conducted to validate the proposed design method. The experimental results show that the system can achieve 3 kW output power with 92.46% DC-DC efficiency and the voltage distribution aggress well with the designed values.
Life Cycle Assessment of Municipal Wastewater Treatment Processes Regarding Energy Production from the Sludge Line
Authors: Szulc Paulina , Kasprzak Jędrzej , Dymaczewski Zbysław , Kurczewski Przemysław
Published: January 2021

The efficient and timely removal of organic matter and nutrients from water used in normal municipal functions is considered to be the main task of wastewater treatment plants (WWTPs). Therefore, these facilities are considered to be essential units that are required to avoid pollution of the water environment and decrease the possibility of triggering eutrophication. Even though these benefits are undeniable, they remain at odds with the high energy demand of wastewater treatment and sludge processes. As a consequence, WWTPs have various environmental impacts, which can be estimated and categorized using Life Cycle Assessment (LCA) analysis. In this study, a municipal WWTP based in Poznań, Poland, was examined using the method defined in ISO 14040. ReCiPe Endpoint and Midpoint (v1.11), in a hierarchical approach, were used to evaluate the environmental impacts regarding 18 different categories. All calculations were conducted using a detailed database from 2019, which describes each chosen facility. It was found that the energy component, related to the wastewater treatment process demand and electricity production, is the main determinant of the sum of the environmental impact indicators in light of the modelled energy mix. Therefore, it determines the entire process as an environmentally friendly activity.
Numerical Investigation of the Impact of H2 Enrichment on Lean Biogas/Air Flames: An Analytical Modelling Approach
Authors: Quintino Filipe M. , Fernandes Edgar C.
Published: January 2021

The transition from natural gas to renewable gases such as biogas and hydrogen creates an interchangeability challenge. The laminar flame speed SL is a critical parameter in appliance design as it is a unique characteristic of the flame mixture. It is thus essential to evaluate the impact of renewable gases on SL. In this work, 1D simulations were conducted in Cantera with the USC-Mech 2.0 kinetic mechanism. The SL of three base biogas blends (BG100, BG90 and BG80) was computed for H2 enrichment up to 50% in volume, equivalence ratio 0.8≤ϕ≤1.0, p=1 atm and Tu=298 K. It was found that the effect of H2 enrichment is higher for base blends with higher CO2 content as the thermal-diffusive and dilution effects of carbon dioxide are mitigated by hydrogen. The introduction of H2 also increases the H radical pool, which is linked with the increase in SL. A new correlation to model the impact of H2 enrichment, SL(xH2)=ζ(ϕ)/SL′(xCO2)xH2exH2+SL′(xCO2), is proposed, which exhibits good agreement with the literature data and simulations. This equation can be directly used to estimate SL without the need for a priori adaptations of fit parameters as the contributions of CO2 and H2 are isolated in independent variables.
Solid Fuel Characteristics of Pellets Comprising Spent Coffee Grounds and Wood Powder
Authors: Woo Duk-Gam , Kim Sang Hyeon , Kim Tae Han
Published: January 2021

To help mitigate the effects of global warming and fossil fuel depletion caused by human use of fossil fuels, solid fuel pellets were developed from a mixture of spent coffee grounds (SCG) and pine sawdust (PS). The feasibility of SCG-PS pellets as biofuel was also verified by evaluating its fuel quality. An increase in the proportion of SCG in the pellet led to an increase in its calorific value, owing to the high C, H, and oil contents, and increases in the ash and S contents, owing to the high S content in SCG. Analysis of the feedstock particle size distribution revealed that SCG particles are smaller than PS particles; thus, the durability of the pellet decreases as the proportion of SCG increases. Accordingly, the samples with higher SCG proportions (70 and 90 wt.%) did not meet the moisture content standards for biomass solid refuse fuel (bio-SRF) set by the Korea Ministry of Environment, whereas the samples with lower SCG proportions did. In particular, CP10 (10 wt.% SCG + 90 wt.% PS) satisfied the quality standards of Grade 1 wood pellets, demonstrating the feasibility of using SCG as a raw material for biofuel pellet production.