bluuebunny/crossref_metadata_2025 huggingface dataset:
Functional and Molecular Properties of DYT-SGCE Myoclonus-Dystonia Patient-Derived Striatal Medium Spiny Neurons
Authors: Kutschenko Anna , Staege Selma , Grütz Karen , Glaß Hannes , Kalmbach Norman , Gschwendtberger Thomas , Henkel Lisa M. , Heine Johanne , Grünewald Anne , Hermann Andreas , Seibler Philip , Wegner Florian
Published: March 2021

Myoclonus-dystonia (DYT-SGCE, formerly DYT11) is characterized by alcohol-sensitive, myoclonic-like appearance of fast dystonic movements. It is caused by mutations in the SGCE gene encoding ε-sarcoglycan leading to a dysfunction of this transmembrane protein, alterations in the cerebello-thalamic pathway and impaired striatal plasticity. To elucidate underlying pathogenic mechanisms, we investigated induced pluripotent stem cell (iPSC)-derived striatal medium spiny neurons (MSNs) from two myoclonus-dystonia patients carrying a heterozygous mutation in the SGCE gene (c.298T>G and c.304C>T with protein changes W100G and R102X) in comparison to two matched healthy control lines. Calcium imaging showed significantly elevated basal intracellular Ca2+ content and lower frequency of spontaneous Ca2+ signals in SGCE MSNs. Blocking of voltage-gated Ca2+ channels by verapamil was less efficient in suppressing KCl-induced Ca2+ peaks of SGCE MSNs. Ca2+ amplitudes upon glycine and acetylcholine applications were increased in SGCE MSNs, but not after GABA or glutamate applications. Expression of voltage-gated Ca2+ channels and most ionotropic receptor subunits was not altered. SGCE MSNs showed significantly reduced GABAergic synaptic density. Whole-cell patch-clamp recordings displayed elevated amplitudes of miniature postsynaptic currents and action potentials in SGCE MSNs. Our data contribute to a better understanding of the pathophysiology and the development of novel therapeutic strategies for myoclonus-dystonia.
The Relationship between the Gut Microbiome and Metformin as a Key for Treating Type 2 Diabetes Mellitus
Authors: Lee Chae Bin , Chae Soon Uk , Jo Seong Jun , Jerng Ui Min , Bae Soo Kyung
Published: March 2021

Metformin is the first-line pharmacotherapy for treating type 2 diabetes mellitus (T2DM); however, its mechanism of modulating glucose metabolism is elusive. Recent advances have identified the gut as a potential target of metformin. As patients with metabolic disorders exhibit dysbiosis, the gut microbiome has garnered interest as a potential target for metabolic disease. Henceforth, studies have focused on unraveling the relationship of metabolic disorders with the human gut microbiome. According to various metagenome studies, gut dysbiosis is evident in T2DM patients. Besides this, alterations in the gut microbiome were also observed in the metformin-treated T2DM patients compared to the non-treated T2DM patients. Thus, several studies on rodents have suggested potential mechanisms interacting with the gut microbiome, including regulation of glucose metabolism, an increase in short-chain fatty acids, strengthening intestinal permeability against lipopolysaccharides, modulating the immune response, and interaction with bile acids. Furthermore, human studies have demonstrated evidence substantiating the hypotheses based on rodent studies. This review discusses the current knowledge of how metformin modulates T2DM with respect to the gut microbiome and discusses the prospect of harnessing this mechanism in treating T2DM.
Mesenchymal Stem Cells as a Cornerstone in a Galaxy of Intercellular Signals: Basis for a New Era of Medicine
Authors: Fernández-Francos Silvia , Eiro Noemi , Costa Luis A. , Escudero-Cernuda Sara , Fernández-Sánchez María Luisa , Vizoso Francisco J.
Published: March 2021

Around 40% of the population will suffer at some point in their life a disease involving tissue loss or an inflammatory or autoimmune process that cannot be satisfactorily controlled with current therapies. An alternative for these processes is represented by stem cells and, especially, mesenchymal stem cells (MSC). Numerous preclinical studies have shown MSC to have therapeutic effects in different clinical conditions, probably due to their mesodermal origin. Thereby, MSC appear to play a central role in the control of a galaxy of intercellular signals of anti-inflammatory, regenerative, angiogenic, anti-fibrotic, anti-oxidative stress effects of anti-apoptotic, anti-tumor, or anti-microbial type. This concept forces us to return to the origin of natural physiological processes as a starting point to understand the evolution of MSC therapy in the field of regenerative medicine. These biological effects, demonstrated in countless preclinical studies, justify their first clinical applications, and draw a horizon of new therapeutic strategies. However, several limitations of MSC as cell therapy are recognized, such as safety issues, handling difficulties for therapeutic purposes, and high economic cost. For these reasons, there is an ongoing tendency to consider the use of MSC-derived secretome products as a therapeutic tool, since they reproduce the effects of their parent cells. However, it will be necessary to resolve key aspects, such as the choice of the ideal type of MSC according to their origin for each therapeutic indication and the implementation of new standardized production strategies. Therefore, stem cell science based on an intelligently designed production of MSC and or their derivative products will be able to advance towards an innovative and more personalized medical biotechnology.
Cytokines Stimulated by IL-33 in Human Skin Mast Cells: Involvement of NF-κB and p38 at Distinct Levels and Potent Co-Operation with FcεRI and MRGPRX2
Authors: Franke Kristin , Wang Zhao , Zuberbier Torsten , Babina Magda
Published: March 2021

The IL-1 family cytokine IL-33 activates and re-shapes mast cells (MCs), but whether and by what mechanisms it elicits cytokines in MCs from human skin remains poorly understood. The current study found that IL-33 activates CCL1, CCL2, IL-5, IL-8, IL-13, and TNF-α, while IL-1β, IL-6, IL-31, and VEGFA remain unaffected in cutaneous MCs, highlighting that each MC subset responds to IL-33 with a unique cytokine profile. Mechanistically, IL-33 induced the rapid (1–2 min) and durable (2 h) phosphorylation of p38, whereas the phosphorylation of JNK was weaker and more transient. Moreover, the NF-κB pathway was potently activated, as revealed by IκB degradation, increased nuclear abundance of p50/p65, and vigorous phosphorylation of p65. The activation of NF-κB occurred independently of p38 or JNK. The induced transcription of the cytokines selected for further study (CCL1, CCL2, IL-8, TNF-α) was abolished by interference with NF-κB, while p38/JNK had only some cytokine-selective effects. Surprisingly, at the level of the secreted protein products, p38 was nearly as effective as NF-κB for all entities, suggesting post-transcriptional involvement. IL-33 did not only instruct skin MCs to produce selected cytokines, but it also efficiently co-operated with the allergic and pseudo-allergic/neurogenic activation networks in the production of IL-8, TNF-α, CCL1, and CCL2. Synergism was more pronounced at the protein than at the mRNA level and appeared stronger for MRGPRX2 ligands than for FcεRI. Our results underscore the pro-inflammatory nature of an acute IL-33 stimulus and imply that especially in combination with allergens or MRGPRX2 agonists, IL-33 will efficiently amplify skin inflammation and thereby aggravate inflammatory dermatoses.
The Role of BDNF in Experimental and Clinical Traumatic Brain Injury
Authors: Gustafsson David , Klang Andrea , Thams Sebastian , Rostami Elham
Published: March 2021

Traumatic brain injury is one of the leading causes of mortality and morbidity in the world with no current pharmacological treatment. The role of BDNF in neural repair and regeneration is well established and has also been the focus of TBI research. Here, we review experimental animal models assessing BDNF expression following injury as well as clinical studies in humans including the role of BDNF polymorphism in TBI. There is a large heterogeneity in experimental setups and hence the results with different regional and temporal changes in BDNF expression. Several studies have also assessed different interventions to affect the BDNF expression following injury. Clinical studies highlight the importance of BDNF polymorphism in the outcome and indicate a protective role of BDNF polymorphism following injury. Considering the possibility of affecting the BDNF pathway with available substances, we discuss future studies using transgenic mice as well as iPSC in order to understand the underlying mechanism of BDNF polymorphism in TBI and develop a possible pharmacological treatment.
The Post-Translational Regulation of Epithelial–Mesenchymal Transition-Inducing Transcription Factors in Cancer Metastasis
Authors: Kang Eunjeong , Seo Jihye , Yoon Haelim , Cho Sayeon
Published: March 2021

Epithelial–mesenchymal transition (EMT) is generally observed in normal embryogenesis and wound healing. However, this process can occur in cancer cells and lead to metastasis. The contribution of EMT in both development and pathology has been studied widely. This transition requires the up- and down-regulation of specific proteins, both of which are regulated by EMT-inducing transcription factors (EMT-TFs), mainly represented by the families of Snail, Twist, and ZEB proteins. This review highlights the roles of key EMT-TFs and their post-translational regulation in cancer metastasis.
Exosomes: Small EVs with Large Immunomodulatory Effect in Glioblastoma
Authors: Benecke Laura , Coray Mali , Umbricht Sandra , Chiang Dapi , Figueiró Fabrício , Muller Laurent
Published: March 2021

Glioblastomas are among the most aggressive tumors, and with low survival rates. They are characterized by the ability to create a highly immunosuppressive tumor microenvironment. Exosomes, small extracellular vesicles (EVs), mediate intercellular communication in the tumor microenvironment by transporting various biomolecules (RNA, DNA, proteins, and lipids), therefore playing a prominent role in tumor proliferation, differentiation, metastasis, and resistance to chemotherapy or radiation. Exosomes are found in all body fluids and can cross the blood–brain barrier due to their nanoscale size. Recent studies have highlighted the multiple influences of tumor-derived exosomes on immune cells. Owing to their structural and functional properties, exosomes can be an important instrument for gaining a better molecular understanding of tumors. Furthermore, they qualify not only as diagnostic and prognostic markers, but also as tools in therapies specifically targeting aggressive tumor cells, like glioblastomas.
Implication of the NLRP3 Inflammasome in Bovine Age-Related Sarcopenia
Authors: De Biase Davide , Piegari Giuseppe , Prisco Francesco , Cimmino Ilaria , d’Aquino Ilaria , Baldassarre Valeria , Oriente Francesco , Papparella Serenella , Paciello Orlando
Published: March 2021

Sarcopenia is defined as the age-related loss of skeletal muscle mass, quality, and strength. The pathophysiological mechanisms underlying sarcopenia are still not completely understood. The aim of this work was to evaluate, for the first time, the expression of NLRP3 inflammasome in bovine skeletal muscle in order to investigate the hypothesis that inflammasome activation may trigger and sustain a pro-inflammatory environment leading to sarcopenia. Samples of skeletal muscle were collected from 60 cattle belonging to three age-based groups. Morphologic, immunohistochemical and molecular analysis were performed to assess the presence of age-related pathologic changes and chronic inflammation, the expression of NLRP3 inflammasome and to determine the levels of interleukin-1β, interleukin-18 and tumor necrosis factor alpha in muscle tissue. Our results revealed the presence of morphologic sarcopenia hallmark, chronic lymphocytic inflammation and a type II fibers-selective NLRP3 expression associated to a significant decreased number of immunolabeled-fibers in aged animals. Moreover, we found a statistically significant age-related increase of pro-inflammatory cytokines such as interleukin-1β and interleukin-18 suggesting the activation of NLRP3 inflammasome. Taken together, our data suggest that NLRP3 inflammasome components may be normally expressed in skeletal muscle, but its priming and activation during aging may contribute to enhance a pro-inflammatory environment altering normal muscular anabolism and metabolism.
Editorial for Special Issue “Lipid as a Cancer Therapeutic Target”
Authors: Albi Elisabetta , Grösch Sabine
Published: March 2021

Lipids are structural components of membranes [...]
The Main Alkaloids in Uncaria rhynchophylla and Their Anti-Alzheimer’s Disease Mechanism Determined by a Network Pharmacology Approach
Authors: Zeng Peng , Wang Xiao-Ming , Ye Chao-Yuan , Su Hong-Fei , Tian Qing
Published: March 2021

Alzheimer’s disease (AD) is a growing concern in modern society, and effective drugs for its treatment are lacking. Uncaria rhynchophylla (UR) and its main alkaloids have been studied to treat neurodegenerative diseases such as AD. This study aimed to uncover the key components and mechanism of the anti-AD effect of UR alkaloids through a network pharmacology approach. The analysis identified 10 alkaloids from UR based on HPLC that corresponded to 90 anti-AD targets. A potential alkaloid target-AD target network indicated that corynoxine, corynantheine, isorhynchophylline, dihydrocorynatheine, and isocorynoxeine are likely to become key components for AD treatment. KEGG pathway enrichment analysis revealed the Alzheimers disease (hsa05010) was the pathway most significantly enriched in alkaloids against AD. Further analysis revealed that 28 out of 90 targets were significantly correlated with Aβ and tau pathology. These targets were validated using a Gene Expression Omnibus (GEO) dataset. Molecular docking studies were carried out to verify the binding of corynoxine and corynantheine to core targets related to Aβ and tau pathology. In addition, the cholinergic synapse (hsa04725) and dopaminergic synapse (hsa04728) pathways were significantly enriched. Our findings indicate that UR alkaloids directly exert an AD treatment effect by acting on multiple pathological processes in AD.
A Comprehensive Review of Genetically Engineered Mouse Models for Prader-Willi Syndrome Research
Authors: Kummerfeld Delf-Magnus , Raabe Carsten A. , Brosius Juergen , Mo Dingding , Skryabin Boris V. , Rozhdestvensky Timofey S.
Published: March 2021

Prader-Willi syndrome (PWS) is a neurogenetic multifactorial disorder caused by the deletion or inactivation of paternally imprinted genes on human chromosome 15q11-q13. The affected homologous locus is on mouse chromosome 7C. The positional conservation and organization of genes including the imprinting pattern between mice and men implies similar physiological functions of this locus. Therefore, considerable efforts to recreate the pathogenesis of PWS have been accomplished in mouse models. We provide a summary of different mouse models that were generated for the analysis of PWS and discuss their impact on our current understanding of corresponding genes, their putative functions and the pathogenesis of PWS. Murine models of PWS unveiled the contribution of each affected gene to this multi-facetted disease, and also enabled the establishment of the minimal critical genomic region (PWScr) responsible for core symptoms, highlighting the importance of non-protein coding genes in the PWS locus. Although the underlying disease-causing mechanisms of PWS remain widely unresolved and existing mouse models do not fully capture the entire spectrum of the human PWS disorder, continuous improvements of genetically engineered mouse models have proven to be very powerful and valuable tools in PWS research.
Construction of Whole Genomes from Scaffolds Using Single Cell Strand-Seq Data
Authors: Hills Mark , Falconer Ester , O’Neill Kieran , Sanders Ashley D. , Howe Kerstin , Guryev Victor , Lansdorp Peter M.
Published: March 2021

Accurate reference genome sequences provide the foundation for modern molecular biology and genomics as the interpretation of sequence data to study evolution, gene expression, and epigenetics depends heavily on the quality of the genome assembly used for its alignment. Correctly organising sequenced fragments such as contigs and scaffolds in relation to each other is a critical and often challenging step in the construction of robust genome references. We previously identified misoriented regions in the mouse and human reference assemblies using Strand-seq, a single cell sequencing technique that preserves DNA directionality Here we demonstrate the ability of Strand-seq to build and correct full-length chromosomes by identifying which scaffolds belong to the same chromosome and determining their correct order and orientation, without the need for overlapping sequences. We demonstrate that Strand-seq exquisitely maps assembly fragments into large related groups and chromosome-sized clusters without using new assembly data. Using template strand inheritance as a bi-allelic marker, we employ genetic mapping principles to cluster scaffolds that are derived from the same chromosome and order them within the chromosome based solely on directionality of DNA strand inheritance. We prove the utility of our approach by generating improved genome assemblies for several model organisms including the ferret, pig, Xenopus, zebrafish, Tasmanian devil and the Guinea pig.
The RARγ Oncogene: An Achilles Heel for Some Cancers
Authors: Brown Geoffrey , Petrie Kevin
Published: March 2021

Cancer “stem cells” (CSCs) sustain the hierarchies of dividing cells that characterize cancer. The main causes of cancer-related mortality are metastatic disease and relapse, both of which originate primarily from CSCs, so their eradication may provide a bona fide curative strategy, though there maybe also the need to kill the bulk cancer cells. While classic anti-cancer chemotherapy is effective against the dividing progeny of CSCs, non-dividing or quiescent CSCs are often spared. Improved anti-cancer therapies therefore require approaches that target non-dividing CSCs, which must be underpinned by a better understanding of factors that permit these cells to maintain a stem cell-like state. During hematopoiesis, retinoic acid receptor (RAR) γ is selectively expressed by stem cells and their immediate progeny. It is overexpressed in, and is an oncogene for, many cancers including colorectal, renal and hepatocellular carcinoma, cholangiocarcinomas and some cases of acute myeloid leukemia that harbor RARγ fusion proteins. In vitro studies suggest that RARγ-selective and pan-RAR antagonists provoke the death of CSCs by necroptosis and point to antagonism of RARγ as a potential strategy to treat metastatic disease and relapse, and perhaps provide a cure for some cancers.
Silk Fiber-Reinforced Hyaluronic Acid-Based Hydrogel for Cartilage Tissue Engineering
Authors: Weitkamp Jan-Tobias , Wöltje Michael , Nußpickel Bastian , Schmidt Felix N. , Aibibu Dilbar , Bayer Andreas , Eglin David , Armiento Angela R. , Arnold Philipp , Cherif Chokri , Lucius Ralph , Smeets Ralf , Kurz Bodo , Behrendt Peter
Published: March 2021

A continuing challenge in cartilage tissue engineering for cartilage regeneration is the creation of a suitable synthetic microenvironment for chondrocytes and tissue regeneration. The aim of this study was to develop a highly tunable hybrid scaffold based on a silk fibroin matrix (SM) and a hyaluronic acid (HA) hydrogel. Human articular chondrocytes were embedded in a porous 3-dimensional SM, before infiltration with tyramine modified HA hydrogel. Scaffolds were cultured in chondropermissive medium with and without TGF-β1. Cell viability and cell distribution were assessed using CellTiter-Blue assay and Live/Dead staining. Chondrogenic marker expression was detected using qPCR. Biosynthesis of matrix compounds was analyzed by dimethylmethylene blue assay and immuno-histology. Differences in biomaterial stiffness and stress relaxation were characterized using a one-step unconfined compression test. Cell morphology was investigated by scanning electron microscopy. Hybrid scaffold revealed superior chondro-inductive and biomechanical properties compared to sole SM. The presence of HA and TGF-β1 increased chondrogenic marker gene expression and matrix deposition. Hybrid scaffolds offer cytocompatible and highly tunable properties as cell-carrier systems, as well as favorable biomechanical properties.
Cardiac Arrhythmias in Survivors of Sudden Cardiac Death Requiring Impella Assist Device Therapy
Authors: Abdullah Khaled Q. A. , Roedler Jana V. , vom Dahl Juergen , Szendey Istvan , Dimitroulis Dimitrios , Eckardt Lars , Topf Albert , Ohnewein Bernhard , Fritsch Lorenz , Föttinger Fabian , Brandt Mathias C. , Wernly Bernhard , Motloch Lukas J. , Larbig Robert
Published: March 2021

In this retrospective single-center trial, we analyze 109 consecutive patients (female: 27.5%, median age: 69 years, median left ventricular ejection fraction: 20%) who survived sudden cardiac death (SCD) and needed hemodynamic support from an Impella assist device between 2008 and 2018. Rhythm monitoring is investigated in this population and associations with hospital survival are analyzed. Hospital mortality is high, at 83.5%. Diverse cardiac arrhythmias are frequently registered during Impella treatment. These include atrial fibrillation (AF, 21.1%) and ventricular tachycardia (VT, 18.3%), as well as AV block II°/III° (AVB, 7.3%), while intermittent asystole (ASY) is the most frequently observed arrhythmia (42.2%). Nevertheless, neither ventricular nor supraventricular tachycardias are associated with patients’ survival. In patients who experience intermittent asystole, a trend towards a fatal outcome is noted (p = 0.06). Conclusions: Mortality is high in these severely sick patients. While cardiac arrhythmias were frequent, they did not predict hospital mortality in this population. The hemodynamic support of the pump seems to counterbalance the adverse effects of these events.
Subthreshold Diode Micropulse Laser Combined with Intravitreal Therapy for Macular Edema—A Systematized Review and Critical Approach
Authors: Gawęcki Maciej
Published: March 2021

Objective: intravitreal therapy for macular edema (ME) is a common clinical approach to treating most retinal vascular diseases; however, it generates high costs and requires multiple follow-up visits. Combining intravitreal anti–vascular endothelial growth factor (VEGF) or steroid therapy with subthreshold diode micropulse laser (SDM) application could potentially reduce the burden of numerous intravitreal injections. This review sought to explore whether this combination treatment is effective in the course of ME secondary to retinal vascular disease, and in particular, determine whether it is comparable or superior to intravitreal therapy alone. Materials and methods: the following terms and Boolean operators were used to search the PubMed literature database: subthreshold micropulse laser, subthreshold diode micropulse OR micropulse laser treatment AND anti-VEGF, anti-VEGF treatment, intravitreal steroids, OR combined therapy.This analysis included all studies discussing the combination of SDM and intravitreal anti-VEGF or steroid treatment. Results: the search revealed nine studies that met the inclusion criteria, including five comparing combined treatment and anti-VEGF treatment alone, four covering diabetic ME, and one covering ME secondary to branch retinal vein occlusion. All of these five studies suggested that combination therapy results in fewer intravitreal injections than anti-VEGF monotherapy with non-inferior functional and morphological outcomes. The remaining four studies report functional and morphological improvements after combined treatment; however, SDM alone was never superior to intravitreal-alone or combined treatment. There were substantial differences in treatment protocols and inclusion criteria between the studies. Conclusions: the available material was too scarce to provide a reliable assessment of the effects of combined therapy and its relation to intravitreal monotherapy in the treatment of ME secondary to retinal vascular disease. One assumption of note is that it is possible that SDM plus anti-VEGF might require fewer intravitreal injections than anti-VEGF monotherapy with equally good functional and morphological results. However, further randomized research is required to confirm this thesis.
A 28 nm CMOS 100 MHz 67 dB-Dynamic-Range 968 µW Flipped-Source-Follower Analog Filter
Authors: De Matteis Marcello , Fary Federico , Vallicelli Elia A. , Baschirotto Andrea
Published: March 2021

This paper presents a fourth-order continuous-time analog filter based on the cascade of two flipped-source-follower (FSF) biquadratic (biquad) cells. The FSF biquad adopts two interacting loops (the first due to the classic source-follower, and the second to the additional gain path) which lower the impedances of all circuit nodes with relevant benefits in terms of noise power reduction and linearity enhancement. The presented device was integrated in 28 nm CMOS and featured 100 MHz −3 dB bandwidth with 67 dB Dynamic-Range. Input IP3 was 12 dBm at 10 and 11 MHz input tone frequencies. Total power consumption was 0.968 mW (0.484 mW per cell). Hence, the filter performed one of the highest figures-of-merit (160.7 dBJ-1) compared with analog state-of-the-art filters.
Strain Induced Surface Change in Sheet Metal Forming: Numerical Prediction, Influence on Friction and Tool Wear
Authors: Wu Yutian , Recklin Viktor , Groche Peter
Published: March 2021

In sheet metal forming, free deformation of the sheet takes place frequently without contact with forming tools. The pre-straining resulting from the free deformation leads to a surface roughening of the sheet metal. It is assumed that the roughening has an influence on friction and wear behavior of the following forming process as well as the painting quality after the manufacturing. In this paper, a numerical prediction based on a polycrystalline model is first proposed to predict the effect of surface roughing based on the material data of the as-received state of the sheet metal. Different states of strain are analyzed and the numerical result is validated through experimental evaluation. Besides the numerical prediction, the friction behavior after pre-straining is evaluated in strip drawing tests and the coefficient of friction (COF) is calculated. For interpretation of the measured COF, the surface roughness after the friction test and the surface image are evaluated by a transparent toolset. It is shown that the surface transformation as a result of pre-straining has a negative influence on the lubricating effect of the sheet metal and degrades the friction behavior. Finally, the influence of the strain-induced surface roughening on wear is discussed based on wear testing in strip drawing test with draw bead geometry.
Resilient Flood Defenses
Authors: Hulscher Suzanne J.M.H. , Warmink Jord J. , Borsje Bas W.
Published: March 2021

Flood risk in deltaic regions is increasing due to a combination of more economic activities and an increase in flooding probability [...]
Fungal Melanin and the Mammalian Immune System
Authors: Liu Sichen , Youngchim Sirida , Zamith-Miranda Daniel , Nosanchuk Joshua D.
Published: March 2021

Melanins are ubiquitous complex polymers that are commonly known in humans to cause pigmentation of our skin. Melanins are also present in bacteria, fungi, and helminths. In this review, we will describe the diverse interactions of fungal melanin with the mammalian immune system. We will particularly focus on Cryptococcus neoformans and also discuss other major melanotic pathogenic fungi. Melanin interacts with the immune system through diverse pathways, reducing the effectiveness of phagocytic cells, binding effector molecules and antifungals, and modifying complement and antibody responses.
Coping with Criticism and Embracing Change—Further Reflexions on the Debate on a Mental Health Care System without Coercion
Authors: von Peter Sebastian , Zinkler Martin
Published: March 2021

In August 2019, a manuscript was published in this journal that aimed at imagining a mental health care system that renounces the judicial control to better focus on the will and preferences of those who require support. Alternative scenarios for dealing with risk, inpatient care, and police custody were presented that elicited strong and emotionally laden reactions. This article adds further reflections to this debate, aiming at contributing explanations for this unsettlement. A productive notion of criticism is discussed, and ways to achieve change toward a more human rights-oriented psychiatric practice are outlined.
Modelling Electron Channeling Contrast Intensity of Stacking Fault and Twin Boundary Using Crystal Thickness Effect
Authors: Kriaa Hana , Guitton Antoine , Maloufi Nabila
Published: March 2021

In a scanning electron microscope, the backscattered electron intensity modulations are at the origin of the contrast of like-Kikuchi bands and crystalline defects. The Electron Channeling Contrast Imaging (ECCI) technique is suited for defects characterization at a mesoscale with transmission electron microscopy-like resolution. In order to achieve a better comprehension of ECCI contrasts of twin-boundary and stacking fault, an original theoretical approach based on the dynamical diffraction theory is used. The calculated backscattered electron intensity is explicitly expressed as function of physical and practical parameters controlling the ECCI experiment. Our model allows, first, the study of the specimen thickness effect on the channeling contrast on a perfect crystal, and thus its effect on the formation of like-Kikuchi bands. Then, our theoretical approach is extended to an imperfect crystal containing a planar defect such as twin-boundary and stacking fault, clarifying the intensity oscillations observed in ECC micrographs.
Kinetics of Austenite Phase Transformations in Newly-Developed 0.17C-2Mn-1Si-0.2Mo Forging Steel with Ti and V Microadditions
Authors: Morawiec Mateusz , Wojtacha Anna , Opiela Marek
Published: March 2021

This work presents the results of phase transformation kinetics during continuous cooling in newly developed high strength low-alloy steel (HSLA). Initial theoretical calculations for the determination of heat treatment parameters were conducted. To determine the structural constituents formed due to the austenite decomposition the dilatometry approach was used. The material was cooled down from the austenitization temperature of 1000 °C with cooling rates between 0.1 °C/s to 60 °C/s. Then, light and scanning electron microscopy investigations were carried out. The microstructure after cooling at rates between 0.1 °C/s up to 1 °C/s is mainly ferritic with some fraction of granular bainite. Increasing the cooling rate led to formation of a higher fraction of bainitic ferrite. At 60 °C/s the microstructure was mainly bainite with some fraction of ferrite. To determine the presence of retained austenite, color etching using Klemm solution was used. The results show that the increase of cooling rate decreases the amount of retained austenite in the microstructure of the steel. Hardness measurements were made to determine the changes in the mechanical properties as a function of the cooling rate.
The Effect of Liquid Rubber Addition on the Physicochemical Properties, Cytotoxicity, and Ability to Inhibit Biofilm Formation of Dental Composites
Authors: Pałka Krzysztof , Miazga-Karska Małgorzata , Pawłat Joanna , Kleczewska Joanna , Przekora Agata
Published: March 2021

The aim of this study was to evaluate the effect of modification with liquid rubber on the adhesion to tooth tissues (enamel, dentin), wettability and ability to inhibit bacterial biofilm formation of resin-based dental composites. Two commercial composites (Flow-Art–flow type with 60% ceramic filler and Boston–packable type with 78% ceramic filler; both from Arkona Laboratorium Farmakologii Stomatologicznej, Nasutów, Poland) were modified by addition of 5% by weight (of resin) of a liquid methacrylate-terminated polybutadiene. Results showed that modification of the flow type composite significantly (p < 0.05) increased the shear bond strength values by 17% for enamel and by 33% for dentine. Addition of liquid rubber significantly (p < 0.05) reduced also hydrophilicity of the dental materials since the water contact angle was increased from 81–83° to 87–89°. Interestingly, modified packable type material showed improved antibiofilm activity against Steptococcus mutans and Streptococcus sanguinis (quantitative assay with crystal violet), but also cytotoxicity against eukaryotic cells since cell viability was reduced to 37% as proven in a direct-contact WST-8 test. Introduction of the same modification to the flow type material significantly improved its antibiofilm properties (biofilm reduction by approximately 6% compared to the unmodified material, p < 0.05) without cytotoxic effects against human fibroblasts (cell viability near 100%). Thus, modified flow type composite may be considered as a candidate to be used as restorative material since it exhibits both nontoxicity and antibiofilm properties.
Numerical Study on the Dependency of Microstructure Morphologies of Pulsed Laser Deposited TiN Thin Films and the Strain Heterogeneities during Mechanical Testing
Authors: Perzynski Konrad , Cios Grzegorz , Szwachta Grzegorz , Bała Piotr , Madej Lukasz
Published: March 2021

Numerical study of the influence of pulsed laser deposited TiN thin films’ microstructure morphologies on strain heterogeneities during loading was the goal of this research. The investigation was based on the digital material representation (DMR) concept applied to replicate an investigated thin film’s microstructure morphology. The physically based pulsed laser deposited model was implemented to recreate characteristic features of a thin film microstructure. The kinetic Monte Carlo (kMC) approach was the basis of the model in the first part of the work. The developed kMC algorithm was used to generate thin film’s three-dimensional representation with its columnar morphology. Such a digital model was then validated with the experimental data from metallographic analysis of laboratory deposited TiN(100)/Si. In the second part of the research, the kMC generated DMR model of thin film was incorporated into the finite element (FE) simulation. The 3D film’s morphology was discretized with conforming finite element mesh, and then incorporated as a microscale model into the macroscale finite element simulation of nanoindentation test. Such a multiscale model was finally used to evaluate the development of local deformation heterogeneities associated with the underlying microstructure morphology. In this part, the capabilities of the proposed approach were clearly highlighted.
Undoped Sr2MMoO6 Double Perovskite Molybdates (M = Ni, Mg, Fe) as Promising Anode Materials for Solid Oxide Fuel Cells
Authors: Skutina Lubov , Filonova Elena , Medvedev Dmitry , Maignan Antoine
Published: March 2021

The chemical design of new functional materials for solid oxide fuel cells (SOFCs) is of great interest as a means for overcoming the disadvantages of traditional materials. Redox stability, carbon deposition and sulfur poisoning of the anodes are positioned as the main processes that result in the degradation of SOFC performance. In this regard, double perovskite molybdates are possible alternatives to conventional Ni-based cermets. The present review provides the fundamental properties of four members: Sr2NiMoO6-δ, Sr2MgMoO6-δ, Sr2FeMoO6-δ and Sr2Fe1.5Mo0.5O6-δ. These properties vary greatly depending on the type and concentration of the 3d-element occupying the B-position of A2BB’O6. The main emphasis is devoted to: (i) the synthesis features of undoped double molybdates, (ii) their electrical conductivity and thermal behaviors in both oxidizing and reducing atmospheres, as well as (iii) their chemical compatibility with respect to other functional SOFC materials and components of gas atmospheres. The information provided can serve as the basis for the design of efficient fuel electrodes prepared from complex oxides with layered structures.
Determination of Physicomechanical Characteristics of the Cement Mortar with Added Fiberglass Waste Treated with Hydrogen Plasma
Authors: Lupu Marius Lucian , Isopescu Dorina Nicolina , Tuns Ioan , Baciu Ioana-Roxana , Maxineasa Sebastian George
Published: March 2021

Solving the environmental problems and the economic aspects of the construction sector represent a global priority. The considerable quantities of raw materials and the energy consumed by this sector make it one of the most polluting economic activities. Fiberglass in various forms is widely used in the construction sector. In the manufacturing process and during the usage of fiberglass products, a significant amount of indestructible waste results, negatively impacting the environment. An innovative solution for utilizing this type of waste is the treatment with hydrogen plasma. This process results in two products: the first in the gaseous state used to obtain synthetic fuel and the second in solid-state, named slag. The composition of solid waste contains chemical compounds that can increase their strength if used as additives in mortars or concretes. This study presents the laboratory tests on mortars, in which a part of the cement amount was replaced with the solid component resulting from the plasma treatment of glass fiber waste. The results showed that replacing a part of the cement with these materials is a solution that minimizes the ecological footprint of the buildings.
Effect of H2O Molecule Adsorption on the Electronic Structure and Optical Properties of the CsI(Na) Crystal
Authors: Liu Fang , Zheng Hao , Jiang Tianze , Liu Bin , Zhang Jianming , Yuan Hang , Liu Fengcheng , Fan Xiaoxue , Ouyang Xiaoping
Published: March 2021

We investigated H2O molecule adsorption that had an effect on the luminescence properties of the CsI(Na) crystal using experiments and first-principle calculations. We measured the emission spectra of the CsI(Na) crystal at different exposure times under gamma ray excitation. The experimental results showed that the energy resolution of the CsI(Na) crystal was worse when the crystal surface adsorbed more H2O molecules, and the crystal surface deliquescence decreased the luminescence efficiency of the CsI(Na) crystal. We studied the band structure, density of states, and optical properties changes caused by H2O molecule adsorption on the CsI(Na) (010) surface. The generalized gradient approximation (GGA) was used to describe the exchange and correlation potential between the electrons. Our calculation results showed that the band gap width of the CsI(Na) (010) surface decreased after adsorbing H2O molecules, while three new peaks appeared in the valence band, and the absorption coefficient decreased from 90,000 cm−1 to 65,000 cm−1, and the reflection coefficient decreased from 0.195 to 0.105. Further, the absorption coefficient was reduced by at least 25% because of H2O molecule adsorption, which led to the luminescence degradation of the CsI(Na) crystal.
Preparation and Characterization of Microcrystalline Wax/Epoxy Resin Microcapsules for Self-Healing of Cementitious Materials
Authors: Du Wei , Liu Quantao , Lin Runsheng , Su Xin
Published: March 2021

Self-healing of cracks in cementitious materials using healing agents encapsulated in microcapsules is an intelligent and effective method. In this study, microcapsules were prepared by the melt–dispersion–condensation method using microcrystalline wax as the shell and E-51 epoxy resin as the healing agent. The effects of preparation process parameters and microcrystalline wax/E-51 epoxy resin weight ratio on the core content, particle size distribution, thermal properties, morphology, and chemical composition of microcapsules were investigated. The results indicated that the optimal parameters of the microcapsule were microcrystalline wax/E-51 epoxy resin weight ratio of 1:1.2, stirring speed of 900 rpm, and preparation temperature of 105 °C. The effects of microcapsules on pore size distribution, pore structure, mechanical properties, permeability, and ultrasonic amplitude of mortar were determined, and the self-healing ability of mortar with different contents of microcapsules was evaluated. The optimal content of microcapsules in mortars was 4% of the cement weight, and the surface cracks of mortar containing microcapsules with an initial width of 0.28 mm were self-healed within three days, indicating that microcapsules have excellent self-healing ability for cementitious materials.
Investigation on the Surface Quality Obtained during Trochoidal Milling of 6082 Aluminum Alloy
Authors: Karkalos Nikolaos E. , Karmiris-Obratański Panagiotis , Kurpiel Szymon , Zagórski Krzysztof , Markopoulos Angelos P.
Published: March 2021

Surface quality has always been an important goal in the manufacturing industry, as it is not only related to the achievement of appropriate geometrical tolerances but also plays an important role in the tribological behavior of the surface as well as its resistance to fatigue and corrosion. Usually, in order to achieve sufficiently high surface quality, process parameters, such as cutting speed and feed, are regulated or special types of cutting tools are used. In the present work, an alternative strategy for slot milling is adopted, namely, trochoidal milling, which employs a more complex trajectory for the cutting tool. Two series of experiments were initially conducted with traditional and trochoidal milling under various feed and cutting speed values in order to evaluate the capabilities of trochoidal milling. The findings showed a clear difference between the two milling strategies, and it was shown that the trochoidal milling strategy is able to provide superior surface quality when the appropriate process parameters are also chosen. Finally, the effect of the depth of cut, coolant and trochoidal stepover on surface roughness during trochoidal milling was also investigated, and it was found that lower depths of cut, the use of coolant and low values of trochoidal stepover can lead to a considerable decrease in surface roughness.
Feature Selection in a Credit Scoring Model
Authors: Laborda Juan , Ryoo Seyong
Published: March 2021

This paper proposes different classification algorithms—logistic regression, support vector machine, K-nearest neighbors, and random forest—in order to identify which candidates are likely to default for a credit scoring model. Three different feature selection methods are used in order to mitigate the overfitting in the curse of dimensionality of these classification algorithms: one filter method (Chi-squared test and correlation coefficients) and two wrapper methods (forward stepwise selection and backward stepwise selection). The performances of these three methods are discussed using two measures, the mean absolute error and the number of selected features. The methodology is applied for a valuable database of Taiwan. The results suggest that forward stepwise selection yields superior performance in each one of the classification algorithms used. The conclusions obtained are related to those in the literature, and their managerial implications are analyzed.
A Systematic Literature Review of Packed Red Cell Transfusion Usage in Adult Extracorporeal Membrane Oxygenation
Authors: Hughes Thomas , Zhang David , Nair Priya , Buscher Hergen
Published: March 2021

Background: Blood product administration plays a major role in the management of patients treated with extracorporeal membrane oxygenation (ECMO) and may be a contributor to morbidity and mortality. Methods: We performed a systematic review of the published literature to determine the current usage of packed red cell transfusions. Predefined search criteria were used to identify journal articles reporting transfusion practice in ECMO by interrogating EMBASE and Medline databases and following the PRISMA statement. Results: Out of 1579 abstracts screened, articles reporting ECMO usage in a minimum of 10 adult patients were included. Full texts of 331 articles were obtained, and 54 were included in the final analysis. All studies were observational (2 were designed prospectively, and two were multicentre). A total of 3808 patients were reported (range 10–517). Mean exposure to ECMO was 8.2 days (95% confidence interval (CI) 7.0–9.4). A median of 5.6% was not transfused (interquartile range (IQR) 0–11.3%, 19 studies). The mean red cell transfusion per ECMO run was 17.7 units (CI 14.2–21.2, from 52 studies) or 2.60 units per day (CI 1.93–3.27, from 49 studies). The median survival to discharge was 50.8% (IQR 40.0–64.9%). Conclusion: Current evidence on transfusion practice in ECMO is mainly drawn from single-centre observational trials and varies widely. The need for transfusions is highly variable. Confounding factors influencing transfusion practice need to be identified in prospective multicentre studies to mitigate potential harmful effects and generate hypotheses for interventional trials.
Determination of Energy Consumption during Turning of Hardened Stainless Steel Using Resultant Cutting Force
Authors: Nur Rusdi , Yusof Noordin Mohd , Sudin Izman , Nor Fethma M. , Kurniawan Denni
Published: March 2021

Downsizing energy consumption during the machining of metals is vital for sustainable manufacturing. As a prerequisite, energy consumption should be determined, through direct or indirect measurement. The manufacturing process of interest is the finish turning which has been explored to generate (near) net shapes, particularly for hardened steels. In this paper, we propose using measured cutting forces to calculate the electrical energy consumption during the finish turning process of metals where typically the depth of cut is lower than the cutting tool nose radius. In this approach, the resultant cutting force should be used for calculating the energy consumption, instead of only the main (tangential) cutting force as used in the conventional approach. A case study was carried out where a hardened stainless steel (AISI 420, hardness of 47–48 HRC) was turned using a coated carbide tool, with a nose radius of 0.8 mm, without cutting fluid, and at 0.4 mm depth of cut. The experimental design varied the cutting speed (100, 130, and 170 m/min) and feed (0.10, 0.125, and 0.16 mm) while other parameters were kept constant. The results indicate that the electrical energy consumption during the particular dry turning of hardened steel can be calculated using cutting force data as proposed. This generally means machining studies that measure cutting forces can also present energy consumption during the finish or hard turning of metals, without specifically measuring the power consumption of the machining process. For this particular dry turning of hardened stainless steel, cutting parameters optimization in terms of machining responses (i.e., low surface roughness, long tool life, low cutting force, and low energy consumption) was also determined to provide an insight on how energy consumption can be integrated with other machining responses towards sustainable machining process of metals.