bluuebunny/crossref_metadata_2025 huggingface dataset:
Chemoinformatics Studies on a Series of Imidazoles as Cruzain Inhibitors
Authors: Medeiros Alex R. , Ferreira Leonardo L. G. , de Souza Mariana L. , de Oliveira Rezende Junior Celso , Espinoza-Chávez Rocío Marisol , Dias Luiz Carlos , Andricopulo Adriano D.
Published: April 2021

Natural products based on imidazole scaffolds have inspired the discovery of a wide variety of bioactive compounds. Herein, a series of imidazoles that act as competitive and potent cruzain inhibitors was investigated using a combination of ligand- and structure-based drug design strategies. Quantitative structure–activity relationships (QSARs) were generated along with the investigation of enzyme–inhibitor molecular interactions. Predictive hologram QSAR (HQSAR, r2pred = 0.80) and AutoQSAR (q2 = 0.90) models were built, and key structural properties that underpin cruzain inhibition were identified. Moreover, comparative molecular field analysis (CoMFA, r2pred = 0.81) and comparative molecular similarity indices analysis (CoMSIA, r2pred = 0.73) revealed 3D molecular features that strongly affect the activity of the inhibitors. These findings were examined along with molecular docking studies and were highly compatible with the intermolecular contacts that take place between cruzain and the inhibitors. The results gathered herein revealed the main factors that determine the activity of the imidazoles studied and provide novel knowledge for the design of improved cruzain inhibitors.
A Theoretical and Simulation Analysis of the Sensitivity of SiNWs-FET Sensors
Authors: Yang Yi , Lu Zicheng , Liu Duo , Wang Yuelin , Chen Shixing , Li Tie
Published: April 2021

Theoretical study and software simulation on the sensitivity of silicon nanowires (SiNWs) field effect transistor (FET) sensors in terms of surface-to-volume ratio, depletion ratio, surface state and lattice quality are carried out. Generally, SiNWs-FET sensors with triangular cross-sections are more sensitive than sensors with circular or square cross-sections. Two main reasons are discussed in this article. Firstly, SiNWs-FET sensors with triangular cross-sections have the largest surface-to-volume ratio and depletion ratio which significantly enhance the sensors’ sensitivity. Secondly, the manufacturing processes of the electron beam lithography (EBL) and chemical vapor deposition (CVD) methods seriously affect the surface state and lattice quality, which eventually influence SiNWs-FET sensors’ sensitivity. In contrast, wet etching and thermal oxidation (WETO) create fewer surface defects and higher quality lattices. Furthermore, the software simulation confirms that SiNWs-FET sensors with triangular cross-sections have better sensitivity than the other two types of SiNWs-FET sensors under the same conditions, consistent with the theoretical analysis. The article fully proved that SiNWs-FET sensors fabricated by the WETO method produced the best sensitivity and it will be widely used in the future.
Bacteriophage-Based Biosensing of Pseudomonas aeruginosa: An Integrated Approach for the Putative Real-Time Detection of Multi-Drug-Resistant Strains
Authors: Harada Liliam K. , Júnior Waldemar Bonventi , Silva Erica C. , Oliveira Thais J. , Moreli Fernanda C. , Júnior José M. Oliveira , Tubino Matthieu , Vila Marta M. D. C. , Balcão Victor M.
Published: April 2021

During the last decennium, it has become widely accepted that ubiquitous bacterial viruses, or bacteriophages, exert enormous influences on our planet’s biosphere, killing between 4–50% of the daily produced bacteria and constituting the largest genetic diversity pool on our planet. Currently, bacterial infections linked to healthcare services are widespread, which, when associated with the increasing surge of antibiotic-resistant microorganisms, play a major role in patient morbidity and mortality. In this scenario, Pseudomonas aeruginosa alone is responsible for ca. 13–15% of all hospital-acquired infections. The pathogen P. aeruginosa is an opportunistic one, being endowed with metabolic versatility and high (both intrinsic and acquired) resistance to antibiotics. Bacteriophages (or phages) have been recognized as a tool with high potential for the detection of bacterial infections since these metabolically inert entities specifically attach to, and lyse, bacterial host cells, thus, allowing confirmation of the presence of viable cells. In the research effort described herein, three different phages with broad lytic spectrum capable of infecting P. aeruginosa were isolated from environmental sources. The isolated phages were elected on the basis of their ability to form clear and distinctive plaques, which is a hallmark characteristic of virulent phages. Next, their structural and functional stabilization was achieved via entrapment within the matrix of porous alginate, biopolymeric, and bio-reactive, chromogenic hydrogels aiming at their use as sensitive matrices producing both color changes and/or light emissions evolving from a reaction with (released) cytoplasmic moieties, as a bio-detection kit for P. aeruginosa cells. Full physicochemical and biological characterization of the isolated bacteriophages was the subject of a previous research paper.
Rapid Molecular Diagnostic Sensor Based on Ball-Lensed Optical Fibers
Authors: Park Byungjun , Koo Bonhan , Kim Jisub , Lee Kiri , Bang Hyeonjin , Kim Sung-Han , Jhang Kyung Young , Shin Yong , Lee Seungrag
Published: April 2021

Given the fatal health conditions caused by emerging infectious pathogens, such as severe acute respiratory syndrome coronavirus 2, their rapid diagnosis is required for preventing secondary infections and guiding correct treatments. Although various molecular diagnostic methods based on nucleic acid amplification have been suggested as gold standards for identifying different species, these methods are not suitable for the rapid diagnosis of pathogens owing to their long result acquisition times and complexity. In this study, we developed a rapid bio-optical sensor that uses a ball-lensed optical fiber (BLOF) probe and an automatic analysis platform to precisely diagnose infectious pathogens. The BLOF probe is easy to align and has a high optical sensing sensitivity (1.5-fold) and a large detection range (1.2-fold) for an automatic optical sensing system. Automatic signal processing of up to 250 copies/reaction of DNA of Q-fever-causing Coxiella burnetii was achieved within 8 min. The clinical utility of this system was demonstrated with 18 clinical specimens (9 Q-fever and 9 other febrile disease samples) by measuring the resonant wavelength shift of positive or negative samples for Coxiella burnetii DNA. The results from the system revealed the stable and automatic optical signal measurement of DNA with 100% accuracy. We envision that this BLOF probe-based sensor would be a practical tool for the rapid, simple, and sensitive diagnosis of emerging infectious pathogens.
Has the COVID 19 Virus Changed Adherence to Hand Washing among Healthcare Workers?
Authors: Ragusa Rosalia , Marranzano Marina , Lombardo Alessandro , Quattrocchi Rosalba , Bellia Maria Alessandra , Lupo Lorenzo
Published: April 2021

The aim of the study was to assess adherence to hand washing by healthcare workers (HCWs) and its variations over time in hospital wards. We wanted to check whether the pandemic had changed the behavior of HCWs. The study was conducted between 1 January 2015, and 31 December 2020. The HCWs were observed to assess their compliance with the Five Moments for Hand Hygiene. We described the percentage of adherence to World Health Organization (WHO) guidelines stratified per year, per specialty areas, per different types of HCWs. We also observed the use of gloves. Descriptive data were reported as frequencies and percentages. We observed 13,494 hand hygiene opportunities. The majority of observations concerned nurses who were confirmed as the category most frequently involved with patients. Hospital’s global adherence to WHO guidelines did not change in the last six years. During the pandemic, the rate of adherence to the procedure increased significantly only in Intensive Care Unit (ICU). In 2020, the use of gloves increased in pre-patient contact. The hand-washing permanent monitoring confirmed that it is very difficult to obtain the respect of correct hand hygiene in all opportunities, despite the ongoing pandemic and the fear of contagion.
Tumor Solid Stress: Assessment with MR Elastography under Compression of Patient-Derived Hepatocellular Carcinomas and Cholangiocarcinomas Xenografted in Mice
Authors: Pagé Gwenaël , Tardieu Marion , Gennisson Jean-Luc , Besret Laurent , Garteiser Philippe , Van Beers Bernard E.
Published: April 2021

Malignant tumors have abnormal biomechanical characteristics, including high viscoelasticity, solid stress, and interstitial fluid pressure. Magnetic resonance (MR) elastography is increasingly used to non-invasively assess tissue viscoelasticity. However, solid stress and interstitial fluid pressure measurements are performed with invasive methods. We studied the feasibility and potential role of MR elastography at basal state and under controlled compression in assessing altered biomechanical features of malignant liver tumors. MR elastography was performed in mice with patient-derived, subcutaneously xenografted hepatocellular carcinomas or cholangiocarcinomas to measure the basal viscoelasticity and the compression stiffening rate, which corresponds to the slope of elasticity versus applied compression. MR elastography measurements were correlated with invasive pressure measurements and digital histological readings. Significant differences in MR elastography parameters, pressure, and histological measurements were observed between tumor models. In multivariate analysis, collagen content and interstitial fluid pressure were determinants of basal viscoelasticity, whereas solid stress, in addition to collagen content, cellularity, and tumor type, was an independent determinant of compression stiffening rate. Compression stiffening rate had high AUC (0.87 ± 0.08) for determining elevated solid stress, whereas basal elasticity had high AUC for tumor collagen content (AUC: 0.86 ± 0.08). Our results suggest that MR elastography compression stiffening rate, in contrast to basal viscoelasticity, is a potential marker of solid stress in malignant liver tumors.
Ginsenoside Rh1 Induces MCF-7 Cell Apoptosis and Autophagic Cell Death through ROS-Mediated Akt Signaling
Authors: Huynh Diem Thi Ngoc , Jin Yujin , Myung Chang-Seon , Heo Kyung-Sun
Published: April 2021

Breast cancer (BC) is the leading cause of cancer-related deaths among women worldwide. Ginsenosides exhibit anticancer activity against various cancer cells. However, the effects of ginsenoside Rh1 on BC and the underlying mechanisms remain unknown. Here, we investigated the anticancer effects of Rh1 on human BC MCF-7 and HCC1428 cells and the underlying signaling pathways. The anticancer effects of Rh1 in vitro were evaluated using sulforhodamine B (SRB), 3-(4, 5-dimethylthiazole-2-yl)-2, 5-diphenyltetrazolium bromide (MTT), clonogenic assay, propidium iodide (PI)/Hoechst staining, Western blotting, flow cytometry, and immunofluorescence analysis. The in vivo effects of Rh1 were determined using a xenograft model via hematoxylin and eosin and the immunohistochemistry staining of tumor tissues. We found that Rh1 exerted cytotoxicity in the cells by increasing cell apoptosis, autophagy, and cell cycle arrest. These effects were further enhanced by a phosphatidylinositol 3-kinase (PI3K) inhibitor but were rescued by the inhibition of reactive oxygen species (ROS). Moreover, enhanced ROS generation by Rh1 inhibited the activation of the PI3K/Akt pathway. Consistently, Rh1 treatment significantly reduced tumor growth in vivo and increased the ROS production and protein expression of LC3B and cleaved caspase-3 but decreased the phosphorylation of Akt and retinoblastoma (Rb) in tumor tissues. Taken together, Rh1 exerted a potential anticancer effect on BC cells by inducing cell cycle arrest, apoptosis, and autophagy via inhibition of the ROS-mediated PI3K/Akt pathway.
Current Intraoperative Imaging Techniques to Improve Surgical Resection of Laryngeal Cancer: A Systematic Review
Authors: Lauwerends Lorraine J. , Galema Hidde A. , Hardillo José A. U. , Sewnaik Aniel , Monserez Dominiek , van Driel Pieter B. A. A. , Verhoef Cornelis , Baatenburg de Jong Robert J. , Hilling Denise E. , Keereweer Stijn
Published: April 2021

Laryngeal cancer is a prevalent head and neck malignancy, with poor prognosis and low survival rates for patients with advanced disease. Treatment consists of unimodal therapy through surgery or radiotherapy in early staged tumors, while advanced stage tumors are generally treated with multimodal chemoradiotherapy or (total) laryngectomy followed by radiotherapy. Still, the recurrence rate for advanced laryngeal cancer is between 25 and 50%. In order to improve surgical resection of laryngeal cancer and reduce local recurrence rates, various intraoperative optical imaging techniques have been investigated. In this systematic review, we identify these technologies, evaluating the current state and future directions of optical imaging for this indication. Narrow-band imaging (NBI) and autofluorescence (AF) are established tools for early detection of laryngeal cancer. Nonetheless, their intraoperative utility is limited by an intrinsic inability to image beyond the (sub-)mucosa. Likewise, contact endoscopy (CE) and optical coherence tomography (OCT) are technically cumbersome and only useful for mucosal margin assessment. Research on fluorescence imaging (FLI) for this application is sparse, dealing solely with nonspecific fluorescent agents. Evidently, the imaging modalities that have been investigated thus far are generally unsuitable for deep margin assessment. We discuss two optical imaging techniques that can overcome these limitations and suggest how they can be used to achieve adequate margins in laryngeal cancer at all stages.
Targeting the Sphingosine Kinase/Sphingosine-1-Phosphate Signaling Axis in Drug Discovery for Cancer Therapy
Authors: Gupta Preeti , Taiyab Aaliya , Hussain Afzal , Alajmi Mohamed F. , Islam Asimul , Hassan Md. Imtaiyaz
Published: April 2021

Sphingolipid metabolites have emerged as critical players in the regulation of various physiological processes. Ceramide and sphingosine induce cell growth arrest and apoptosis, whereas sphingosine-1-phosphate (S1P) promotes cell proliferation and survival. Here, we present an overview of sphingolipid metabolism and the compartmentalization of various sphingolipid metabolites. In addition, the sphingolipid rheostat, a fine metabolic balance between ceramide and S1P, is discussed. Sphingosine kinase (SphK) catalyzes the synthesis of S1P from sphingosine and modulates several cellular processes and is found to be essentially involved in various pathophysiological conditions. The regulation and biological functions of SphK isoforms are discussed. The functions of S1P, along with its receptors, are further highlighted. The up-regulation of SphK is observed in various cancer types and is also linked to radio- and chemoresistance and poor prognosis in cancer patients. Implications of the SphK/S1P signaling axis in human pathologies and its inhibition are discussed in detail. Overall, this review highlights current findings on the SphK/S1P signaling axis from multiple angles, including their functional role, mechanism of activation, involvement in various human malignancies, and inhibitor molecules that may be used in cancer therapy.
Lights and Shadows on Managing Immune Checkpoint Inhibitors in Oncology during the COVID-19 Era
Authors: Burgaletto Chiara , Brunetti Oronzo , Munafò Antonio , Bernardini Renato , Silvestris Nicola , Cantarella Giuseppina , Argentiero Antonella
Published: April 2021

Since the start of the global spread of coronavirus disease (COVID-19) pandemic, cancer patients were identified as a specifically susceptible subgroup of the patient population. Several reports have shown that cancer patients have an increased risk of both contracting the infection and of experiencing a more severe disease course, with a rapidly evolving picture associated with higher mortality. The assumption of cancer patients as “COVID-19 vulnerable” has led, irretrievably, to profound changes in the decision making of oncological treatments. Potential justifications for such concerns encompass the cancer-dependent suppression of the immune response, as well as the influence of administration of systemic anticancer treatments, including chemotherapy and immunotherapy. Nevertheless, to date, it is not clear whether the use of immune checkpoint inhibitors (ICIs) in cancer patients is safe, given their modulating effects on the immune system, or that they may rather conceal detrimental consequences. Theoretically, on the one hand, ICIs may enhance the immunological control of viral infections through their immunostimulating mechanisms; on the other hand, they could contribute to the hyper-inflammatory phase of COVID-19, worsening its clinical outcomes. In this study, we report the foremost clinical observations on the safety of ICI administration in cancer patients affected by COVID-19.
Activation of Cilia-Independent Hedgehog/GLI1 Signaling as a Novel Concept for Neuroblastoma Therapy
Authors: Koeniger Anke , Brichkina Anna , Nee Iris , Dempwolff Lukas , Hupfer Anna , Galperin Ilya , Finkernagel Florian , Nist Andrea , Stiewe Thorsten , Adhikary Till , Diederich Wibke , Lauth Matthias
Published: April 2021

Although being rare in absolute numbers, neuroblastoma (NB) represents the most frequent solid tumor in infants and young children. Therapy options and prognosis are comparably good for NB patients except for the high risk stage 4 class. Particularly in adolescent patients with certain genetic alterations, 5-year survival rates can drop below 30%, necessitating the development of novel therapy approaches. The developmentally important Hedgehog (Hh) pathway is involved in neural crest differentiation, the cell type being causal in the etiology of NB. However, and in contrast to its function in some other cancer types, Hedgehog signaling and its transcription factor GLI1 exert tumor-suppressive functions in NB, rendering GLI1 an interesting new candidate for anti-NB therapy. Unfortunately, the therapeutic concept of pharmacological Hh/GLI1 pathway activation is difficult to implement as NB cells have lost primary cilia, essential organelles for Hh perception and activation. In order to bypass this bottleneck, we have identified a GLI1-activating small molecule which stimulates endogenous GLI1 production without the need for upstream Hh pathway elements such as Smoothened or primary cilia. This isoxazole compound potently abrogates NB cell proliferation and might serve as a starting point for the development of a novel class of NB-suppressive molecules.
Prognostic Value of the Immunological Subtypes of Adolescent and Adult T-Cell Lymphoblastic Lymphoma; an Ultra-High-Risk Pro-T/CD2(−) Subtype
Authors: Ostrowska Beata , Rymkiewicz Grzegorz , Chechlinska Magdalena , Blachnio Katarzyna , Domanska-Czyz Katarzyna , Bystydzienski Zbigniew , Romejko-Jarosinska Joanna , Borysiuk Anita , Rybski Sebastian , Michalski Wojciech , Walewski Jan
Published: April 2021

(1) Background: T-cell lymphoblastic lymphoma (T-LBL) is extremely rare and highly aggressive, with no practical risk model defined yet. The prognostic value of T-LBL immunological subtypes is still a matter of controversy. (2) Methods: We re-evaluated 49 subsequent adult T-LBL patients treated according to the German Multicenter Study Group for Adult Acute Lymphoblastic Leukemia (GMALL) protocols, 05/93 (n = 20) and T-LBL 1/2004 (n = 29), 85.7% of which achieved complete remission (CR). (3) Results: The 5/10-year overall survival (OS) and event-free survival (EFS) were 62%/59% and 48%/43%, respectively. In 96% of patients, flow cytometry analyses defining the WHO 2008 immunophenotypes were available. Cortical, early/pro-T/CD2(−), early/pre-T/CD2(+), and mature subtypes were identified in 59.5%, 19%, 15%, and 6.5% of patients, respectively. Overall, 20% of patients had the early T-cell precursor (ETP)-LBL immunophenotype, as proposed by the WHO 2017 classification. For the early/pro-T/CD2(−) subtype, the five-year OS and EFS were 13% and 13%, while for all the other, non-pro-T subtypes, they were 69% and 67%. By multivariate analysis, only CD2(−) status and age > 35 years emerged as strong, independent factors influencing OS and EFS, while the risk of CR failure was influenced by age only (>35 years). (4) Conclusions: ETP was non-significant for OS, unless an ultra-high-risk pro-T/CD2(−) subtype was concerned.
Induced Torpor as a Countermeasure for Low Dose Radiation Exposure in a Zebrafish Model
Authors: Cahill Thomas , da Silveira Willian Abraham , Renaud Ludivine , Williamson Tucker , Wang Hao , Chung Dongjun , Overton Ian , Chan Sherine S. L. , Hardiman Gary
Published: April 2021

The development of the Artemis programme with the goal of returning to the moon is spurring technology advances that will eventually take humans to Mars and herald a new era of interplanetary space travel. However, long-term space travel poses unique challenges including exposure to ionising radiation from galactic cosmic rays and potential solar particle events, exposure to microgravity and specific nutritional challenges arising from earth independent exploration. Ionising radiation is one of the major obstacles facing future space travel as it can generate oxidative stress and directly damage cellular structures such as DNA, in turn causing genomic instability, telomere shortening, extracellular-matrix remodelling and persistent inflammation. In the gastrointestinal tract (GIT) this can lead to leaky gut syndrome, perforations and motility issues, which impact GIT functionality and affect nutritional status. While current countermeasures such as shielding from the spacecraft can attenuate harmful biological effects, they produce harmful secondary particles that contribute to radiation exposure. We hypothesised that induction of a torpor-like state would confer a radioprotective effect given the evidence that hibernation extends survival times in irradiated squirrels compared to active controls. To test this hypothesis, a torpor-like state was induced in zebrafish using melatonin treatment and reduced temperature, and radiation exposure was administered twice over the course of 10 days. The protective effects of induced-torpor were assessed via RNA sequencing and qPCR of mRNA extracted from the GIT. Pathway and network analysis were performed on the transcriptomic data to characterise the genomic signatures in radiation, torpor and torpor + radiation groups. Phenotypic analyses revealed that melatonin and reduced temperature successfully induced a torpor-like state in zebrafish as shown by decreased metabolism and activity levels. Genomic analyses indicated that low dose radiation caused DNA damage and oxidative stress triggering a stress response, including steroidal signalling and changes to metabolism, and cell cycle arrest. Torpor attenuated the stress response through an increase in pro-survival signals, reduced oxidative stress via the oxygen effect and detection and removal of misfolded proteins. This proof-of-concept model provides compelling initial evidence for utilizing an induced torpor-like state as a potential countermeasure for radiation exposure.
Not So Dead Genes—Retrocopies as Regulators of Their Disease-Related Progenitors and Hosts
Authors: Ciomborowska-Basheer Joanna , Staszak Klaudia , Kubiak Magdalena Regina , Makałowska Izabela
Published: April 2021

Retroposition is RNA-based gene duplication leading to the creation of single exon nonfunctional copies. Nevertheless, over time, many of these duplicates acquire transcriptional capabilities. In human in most cases, these so-called retrogenes do not code for proteins but function as regulatory long noncoding RNAs (lncRNAs). The mechanisms by which they can regulate other genes include microRNA sponging, modulation of alternative splicing, epigenetic regulation and competition for stabilizing factors, among others. Here, we summarize recent findings related to lncRNAs originating from retrocopies that are involved in human diseases such as cancer and neurodegenerative, mental or cardiovascular disorders. Special attention is given to retrocopies that regulate their progenitors or host genes. Presented evidence from the literature and our bioinformatics analyses demonstrates that these retrocopies, often described as unimportant pseudogenes, are significant players in the cell’s molecular machinery.
Microstructure, Mechanical Properties and Tribological Behavior of Magnetron-Sputtered MoS2 Solid Lubricant Coatings Deposited under Industrial Conditions
Authors: Seynstahl Armin , Krauß Sebastian , Bitzek Erik , Meyer Bernd , Merle Benoit , Tremmel Stephan
Published: April 2021

Depositing MoS2 coatings for industrial applications involves rotating the samples during the PVD magnetron sputtering process. Here, we show that a 3-fold substrate rotation, along a large target–substrate distance given by the deposition unit, introduces porosity inside the coatings. The mechanical properties and wear behavior strongly correlate with the degree of porosity, which, in turn, depends on the temperature and the rotational speed of the substrate. Ball-on-disk tests and nanoindentation wear experiments show a consistent change in tribological behavior; first, a compaction of the porous structure dominates, followed by wear of the compacted material. Compaction was the main contributor to the volume loss during the running-in process. Compared to a dense coating produced without substrate rotation, the initially porous coatings showed lower hardness and a distinct running-in behavior. Tribological lifetime experiments showed good lubrication performance after compaction.
Influence of Multi-Pass Hot Extrusion on Microstructure and Mechanical Properties of the Mg–4Zn–1.2Y–0.8Nd Alloy
Authors: Sheng Liyuan , Zhang Xingru , Zhao Hui , Du Beining , Zheng Yufeng , Xi Tingfei
Published: April 2021

In the present research, a Mg–4Zn–1.2Y–0.8Nd (wt.%) alloy was heat treated and hot extruded with different passes. XRD, SEM, TEM and tensile testing were employed to characterize the microstructure evolution and mechanical properties. The results exhibited that the semi-continuously distributed W-Mg3Zn3Y2 phases formed the skeleton structure which separated the α-Mg matrix into a dual-size grain structure. In addition, the Mg24Y5, Mg41Nd5 and Y2O3 phase was also observed in the heat-treated alloy. Moreover, it was found that the Mg24Y5 phase had an orientation relationship with the α-Mg matrix of α[111]Mg24Y5//[0001]α-Mg and α(101¯)Mg24Y5//(101¯0)α-Mg, and the Mg41Nd5 phase had an orientation relationship with the α-Mg matrix of α[001]Mg41Nd5//[0001]α-Mg. The one-pass hot extrusion segmented the secondary phases into small ones and refined the α-Mg matrix. Due to the partly recrystallization and crystal orientation difference, the coarse elongated grain surrounded by fine recrystallized grain and secondary phase was the main feature of the one-pass hot extruded alloy. Furthermore, the secondary phases exhibited the linear distribution along the direction of hot extrusion. The two-pass hot extrusion refined the secondary phase and matrix further, which produced the ultrafine α-Mg matrix with uniform grain size and a well redistributed secondary phase. Due to the microstructure optimization by the multi-pass hot extrusion, the ductility and strength of the Mg–Zn–Y–Nd alloy were well improved, especially the two-pass hot extruded alloy which was significant improved in ductility and strength simultaneously.
Melanocyte Colonization and Pigmentation of Breast Carcinoma: Description of Two Pathological Cases and Review of Literature
Authors: Santoro Angela , Angelico Giuseppe , Fiorentino Vincenzo , Zhang Qianqian , Spadola Saveria , Carlino Angela , Sanchez Alejandro Martin , Franceschini Gianluca , Zannoni Gian Franco , Mulè Antonino
Published: April 2021

Colonization of breast carcinoma by non-neoplastic melanocytes of epidermal origin was first described by Azzopardi and Eusebi in 1977. We herein report two cases on the exceptional clinical and pathological features of this phenomenon in a 66-year-old and a 51-year-old patients. The pathogenesis is not fully understood, but a disrupted basement membrane and the role of tumoral growth factors are considered essential.
Renal Diseases Associated with Hematologic Malignancies and Thymoma in the Absence of Renal Monoclonal Immunoglobulin Deposits
Authors: Morel Antoine , Meuleman Marie-Sophie , Moktefi Anissa , Audard Vincent
Published: April 2021

In addition to kidney diseases characterized by the precipitation and deposition of overproduced monoclonal immunoglobulin and kidney damage due to chemotherapy agents, a broad spectrum of renal lesions may be found in patients with hematologic malignancies. Glomerular diseases, in the form of paraneoplastic glomerulopathies and acute kidney injury with various degrees of proteinuria due to specific lymphomatous interstitial and/or glomerular infiltration, are two major renal complications observed in the lymphoid disorder setting. However, other hematologic neoplasms, including chronic lymphocytic leukemia, thymoma, myeloproliferative disorders, Castleman disease and hemophagocytic syndrome, have also been associated with the development of kidney lesions. These renal disorders require prompt recognition by the clinician, due to the need to implement specific treatment, depending on the chemotherapy regimen, to decrease the risk of subsequent chronic kidney disease. In the context of renal disease related to hematologic malignancies, renal biopsy remains crucial for accurate pathological diagnosis, with the aim of optimizing medical care for these patients. In this review, we provide an update on the epidemiology, clinical presentation, pathophysiological processes and diagnostic strategy for kidney diseases associated with hematologic malignancies outside the spectrum of monoclonal gammopathy of renal significance.
Suppressing Buffer-Induced Current Collapse in GaN HEMTs with a Source-Connected p-GaN (SCPG): A Simulation Study
Authors: Lin Wei , Wang Maojun , Sun Haozhe , Xie Bing , Wen Cheng P. , Hao Yilong , Shen Bo
Published: April 2021

Carbon doping in the buffer of AlGaN/GaN high-electron-mobility transistors (HEMTs) leads to the notorious current collapse phenomenon. In this paper, an HEMT structure with a source-connected p-GaN (SCPG) embedded in the carbon-doped semi-insulating buffer is proposed to suppress the buffer-induced current collapse effect. Two-dimensional transient simulation was carried out to show the successful suppression of buffer-induced current collapse in the SCPG-HEMTs compared with conventional HEMTs. The mechanism of suppressing dynamic on-resistance degradation by ejecting holes from the SCPG into the high resistive buffer layer after off-state stress is illustrated based on energy band diagrams. This paper contributes an innovative device structure to potentially solve the buffer-induced degradation of the dynamic on-resistance in GaN power devices.
Artificial Immune System for Fault Detection and Classification of Semiconductor Equipment
Authors: Park Hyoeun , Choi Jeong Eun , Kim Dohyun , Hong Sang Jeen
Published: April 2021

Semiconductor manufacturing comprises hundreds of consecutive unit processes. A single misprocess could jeopardize the whole manufacturing process. In current manufacturing environments, data monitoring of equipment condition, wafer metrology, and inspection, etc., are used to probe any anomaly during the manufacturing process that could affect the final chip performance and quality. The purpose of investigation is fault detection and classification (FDC). Various methods, such as statistical or data mining methods with machine learning algorithms, have been employed for FDC. In this paper, we propose an artificial immune system (AIS), which is a biologically inspired computing algorithm, for FDC regarding semiconductor equipment. Process shifts caused by parts and modules aging over time are main processes of failure cause. We employ state variable identification (SVID) data, which contain current equipment operating condition, and optical emission spectroscopy (OES) data, which represent plasma process information obtained from faulty process scenario with intentional modification of the gas flow rate in a semiconductor fabrication process. We achieved a modeling prediction accuracy of modeling of 94.69% with selected SVID and OES and an accuracy of 93.68% with OES data alone. To conclude, the possibility of using an AIS in the field of semiconductor process decision making is proposed.
Using CFD to Evaluate Natural Ventilation through a 3D Parametric Modeling Approach
Authors: Rodrigues Marques Sakiyama Nayara , Frick Jurgen , Bejat Timea , Garrecht Harald
Published: April 2021

Predicting building air change rates is a challenge for designers seeking to deal with natural ventilation, a more and more popular passive strategy. Among the methods available for this task, computational fluid dynamics (CFD) appears the most compelling, in ascending use. However, CFD simulations require a range of settings and skills that inhibit its wide application. With the primary goal of providing a pragmatic CFD application to promote wind-driven ventilation assessments at the design phase, this paper presents a study that investigates natural ventilation integrating 3D parametric modeling and CFD. From pre- to post-processing, the workflow addresses all simulation steps: geometry and weather definition, including incident wind directions, a model set up, control, results’ edition, and visualization. Both indoor air velocities and air change rates (ACH) were calculated within the procedure, which used a test house and air measurements as a reference. The study explores alternatives in the 3D design platform’s frame to display and compute ACH and parametrically generate surfaces where air velocities are computed. The paper also discusses the effectiveness of the reference building’s natural ventilation by analyzing the CFD outputs. The proposed approach assists the practical use of CFD by designers, providing detailed information about the numerical model, as well as enabling the means to generate the cases, visualize, and post-process the results.
Improved Self-Sensing Speed Control of IPMSM Drive Based on Cascaded Nonlinear Control
Authors: Usama Muhammad , Kim Jaehong
Published: April 2021

This paper presents a nonlinear cascaded control design that has been developed to (1) improve the self-sensing speed control performance of an interior permanent magnet synchronous motor (IPMSM) drive by reducing its speed and torque ripples and its phase current harmonic distortion and (2) attain the maximum torque while utilizing the minimum drive current. The nonlinear cascaded control system consists of two nonlinear controls for the speed and current control loop. A fuzzy logic controller (FLC) is employed for the outer speed control loop to regulate the rotor shaft speed. Model predictive current control (MPCC) is utilized for the inner current control loop to regulate the drive phase currents. The nonlinear equation for the dq reference current is derived to implement the maximum torque per armature (MTPA) control to achieve the maximum torque while using the minimum current values. The model reference adaptive system (MRAS) was employed for the speed self-sensing mechanism. The self-sensing speed control performance of the IPMSM motor drive was compared with that of the traditional cascaded control schemes. The stability of the sensorless mechanism was studied using the pole placement method. The proposed nonlinear cascaded control was verified based on the simulation results. The robustness of the control design was ensured under various loads and in a wide speed range. The dynamic performance of the motor drive is improved while circumventing the need to tune the proportional-integral (PI) controller. The self-sensing speed control performance of the IPMSM drive was enhanced significantly by the designed cascaded control model.
Protected Areas in Forest Conservation: Challenges and Opportunities
Authors: Dimitrakopoulos Panayiotis G. , Jones Nikoleta
Published: April 2021

Forest ecosystems are important habitats for a vast number of species worldwide [...]
Bacterial Spore Inactivation in Orange Juice and Orange Peel by Ultraviolet-C Light
Authors: Colás-Medà Pilar , Nicolau-Lapeña Iolanda , Viñas Inmaculada , Neggazi Isma , Alegre Isabel
Published: April 2021

Spore-forming bacteria are a great concern for fruit juice processors as they can resist the thermal pasteurization and the high hydrostatic pressure treatments that fruit juices receive during their processing, thus reducing their microbiological quality and safety. In this context, our objective was to evaluate the efficacy of Ultraviolet-C (UV-C) light at 254 nm on reducing bacterial spores of Alicyclobacillus acidoterrestris, Bacillus coagulans and Bacillus cereus at two stages of orange juice production. To simulate fruit disinfection before processing, the orange peel was artificially inoculated with each of the bacterial spores and submitted to UV-C light (97.8–100.1 W/m2) with treatment times between 3 s and 10 min. The obtained product, the orange juice, was also tested by exposing the artificially inoculated juice to UV-C light (100.9–107.9 W/m2) between 5 and 60 min. A three-minute treatment (18.0 kJ/m2) reduced spore numbers on orange peel around 2 log units, while more than 45 min (278.8 kJ/m2) were needed to achieve the same reduction in orange juice for all evaluated bacterial spores. As raw fruits are the main source of bacterial spores in fruit juices, reducing bacterial spores on fruit peels could help fruit juice processors to enhance the microbiological quality and safety of fruit juices.
A Narrative Review on Dietary Strategies to Provide Nitric Oxide as a Non-Drug Cardiovascular Disease Therapy: Beetroot Formulations—A Smart Nutritional Intervention
Authors: dos Santos Baião Diego , Vieira Teixeira da Silva Davi , Margaret Flosi Paschoalin Vania
Published: April 2021

Beetroot is a remarkable vegetable, as its rich nitrate and bioactive compound contents ameliorate cardiovascular and metabolic functions by boosting nitric oxide synthesis and regulating gene expressions or modulating proteins and enzyme activities involved in these cellular processes. Dietary nitrate provides a physiological substrate for nitric oxide production, which promotes vasodilatation, increases blood flow and lowers blood pressure. A brief narrative and critical review on dietary nitrate intake effects are addressed herein by considering vegetable sources, dosage, intervention regimen and cardioprotective effects achieved in both healthy and cardiovascular-susceptible individuals. Compared to other nitrate-rich vegetables, beets were proven to be the best choice for non-drug therapy because of their sensorial characteristics and easy formulations that facilitate patient adherence for long periods, allied to bioaccessibility and consequent effectiveness. Beets were shown to be effective in raising nitrate and nitrite in biological fluids at levels capable of promoting sustained improvement in primary and advanced hemodynamic parameters.
Azoxymethane-Induced Colorectal Cancer Mice Treated with a Polyphenol-Rich Apple Extract Show Less Neoplastic Lesions and Signs of Cachexia
Authors: Marzo Florencio , Milagro Fermin I. , Barrenetxe Jaione , Díaz María Teresa , Martínez J. Alfredo
Published: April 2021

Obesity is considered a risk factor for the development of colorectal cancer. In rodents, high-fat (HF) diets are able to increase the formation of azoxymethane (AOM)-induced polyps. Polyphenol-rich apple extracts have antioxidant and anti-inflammatory activities and may induce an amelioration of the manifestations of colorectal cancer. Twenty-seven male Crl:CD-1 mice received AOM during four weeks and were subsequently divided into three groups fed a HF diet (n = 9 each group): a non-supplemented group, a second group supplemented with apple extract at 1%, and a third group supplemented with the same apple extract at 1.5%. Energy metabolism and the respiratory quotient were not affected by the supplementation with the apple extract. Although body weight was not affected by the treatment, the mice supplemented with the apple extract showed less signs of cachexia than the non-treated mice. In the intestine, the mice supplemented with the apple extract showed lower sucrase, dipeptidyl-peptidase IV, and aminopeptidase N activities, and less intestinal lesions (aberrant crypt foci and polyps). Administration of a polyphenol-rich apple extract reduces the number of neoplastic lesions in mice with AOM-induced colorectal cancer and contributes to preserve adipose tissue mass.
Cold Brew Coffee—Pilot Studies on Definition, Extraction, Consumer Preference, Chemical Characterization and Microbiological Hazards
Authors: Claassen Linda , Rinderknecht Maximilian , Porth Theresa , Röhnisch Julia , Seren Hatice Yasemin , Scharinger Andreas , Gottstein Vera , Noack Daniela , Schwarz Steffen , Winkler Gertrud , Lachenmeier Dirk W.
Published: April 2021

Cold brew coffee is a new trend in the coffee industry. This paper presents pilot studies on several aspects of this beverage. Using an online survey, the current practices of cold brew coffee preparation were investigated, identifying a rather large variability with a preference for extraction of medium roasted Arabica coffee using 50–100 g/L at 8 °C for about 1 day. Sensory testing using ranking and triangle tests showed that cold brew may be preferred over iced coffee (cooled down hot extracted coffee). Extraction experiments under different conditions combined with nuclear magnetic resonance (NMR) analysis showed that the usual extraction time may be longer than necessary as most compounds are extracted within only a few hours, while increasing turbulence (e.g., using ultrasonication) and temperature may additionally increase the speed of extraction. NMR analysis also revealed a possible chemical differentiation between cold brew and hot brew using multivariate data analysis. Decreased extraction time and reduced storage times could be beneficial for cold brew product quality as microbiological analysis of commercial samples detected samples with spoilage organisms and contamination with Bacillus cereus.
Fairness and Efficiency in Online Advertising Mechanisms
Authors: Watts Alison
Published: April 2021

Online advertising often involves targeting ads to certain types of consumers where ads are commonly sold by generalized second price auctions. However, such an auction or mechanism could be considered unfair if similar consumers are consistently shown different ads or consistently receive different payoffs. Results show that such ascending bid auctions may result in unfair treatment and additionally that uncertainty regarding an ad’s value can result in inefficiency. An alternative way to assign ads to consumers is presented called the random assignment mechanism. Results show that the random assignment can improve fairness while improving efficiency in some circumstances.
Predicting TCR-Epitope Binding Specificity Using Deep Metric Learning and Multimodal Learning
Authors: Luu Alan , Leistico Jacob , Miller Tim , Kim Somang , Song Jun
Published: April 2021

Understanding the recognition of specific epitopes by cytotoxic T cells is a central problem in immunology. Although predicting binding between peptides and the class I Major Histocompatibility Complex (MHC) has had success, predicting interactions between T cell receptors (TCRs) and MHC class I-peptide complexes (pMHC) remains elusive. This paper utilizes a convolutional neural network model employing deep metric learning and multimodal learning to perform two critical tasks in TCR-epitope binding prediction: identifying the TCRs that bind a given epitope from a TCR repertoire, and identifying the binding epitope of a given TCR from a list of candidate epitopes. Our model can perform both tasks simultaneously and reveals that inconsistent preprocessing of TCR sequences can confound binding prediction. Applying a neural network interpretation method identifies key amino acid sequence patterns and positions within the TCR, important for binding specificity. Contrary to common assumption, known crystal structures of TCR-pMHC complexes show that the predicted salient amino acid positions are not necessarily the closest to the epitopes, implying that physical proximity may not be a good proxy for importance in determining TCR-epitope specificity. Our work thus provides an insight into the learned predictive features of TCR-epitope binding specificity and advances the associated classification tasks.
Genetic Profiling of Idiopathic Antenatal Intracranial Haemorrhage: What We Know?
Authors: Cavaliere Anna Franca , Turrini Irene , Pallottini Marta , Vidiri Annalisa , Marchi Laura , Perelli Federica , Zaami Simona , Scambia Giovanni , Signore Fabrizio
Published: April 2021

Intracranial hemorrhage (ICH) is reported in premature infants and rarely, in prenatal life. Fetal ICH can be accurately identified in utero and categorized by antenatal sonography and/or MRI. Infectious disease, maternal drug exposure, alloimmune thrombocytopenia, maternal trauma, coagulation disorders and twin-to-twin transfusion syndrome can cause fetal ICH. However, in many cases, the cause is not identified and a genetic disorder should be taken into consideration. We conducted a review of the literature to investigate what we know about genetic origins of fetal ICH. We conducted targeted research on the databases PubMed and EMBASE, ranging from 1980 to 2020. We found 311 studies and 290 articles were excluded because they did not meet the inclusion criteria, and finally, 21 articles were considered relevant for this review. Hemostatic, protrombotic, collagen and X-linked GATA 1 genes were reported in the literature as causes of fetal ICH. In cases of ICH classified as idiopathic, possible underlying genetic causes should be accounted for and investigated. The identification of ICH genetic causes can guide the counselling process with respect to the recurrence risk, in addition to producing relevant clinical data to the neonatologist for the optimal management and prompt treatment of the newborn.