bluuebunny/crossref_metadata_2025 huggingface dataset:
Stochastic Time Response and Ultimate Noise Performance of Adsorption-Based Microfluidic Biosensors
Authors: Jokić Ivana , Djurić Zoran , Radulović Katarina , Frantlović Miloš , Milovanović Gradimir V. , Krstajić Predrag M.
Published: June 2021

In order to improve the interpretation of measurement results and to achieve the optimal performance of microfluidic biosensors, advanced mathematical models of their time response and noise are needed. The random nature of adsorption–desorption and mass transfer (MT) processes that generate the sensor response makes the sensor output signal inherently stochastic and necessitates the use of a stochastic approach in sensor response analysis. We present a stochastic model of the sensor time response, which takes into account the coupling of adsorption–desorption and MT processes. It is used for the analysis of response kinetics and ultimate noise performance of protein biosensors. We show that slow MT not only decelerates the response kinetics, but also increases the noise and decreases the sensor’s maximal achievable signal-to-noise ratio, thus degrading the ultimate sensor performance, including the minimal detectable/quantifiable analyte concentration. The results illustrate the significance of the presented model for the correct interpretation of measurement data, for the estimation of sensors’ noise performance metrics important for reliable analyte detection/quantification, as well as for sensor optimization in terms of the lower detection/quantification limit. They are also incentives for the further investigation of the MT influence in nanoscale sensors, as a possible cause of false-negative results in analyte detection experiments.
Study on a Plasmonic Tilted Fiber Grating-Based Biosensor for Calmodulin Detection
Authors: Chen Xiaoyong , Jiang Jie , Zhang Nan , Lin Wenwei , Xu Pin , Sun Jinghua
Published: June 2021

Tilted fiber Bragg grating, which has the advantages of both fiber Bragg grating and long-period fiber grating, has been widely studied for sensing in many fields, especially in the field of biochemistry. Calmodulin, which has a wide distribution in eukaryotes, can regulate several enzymes such as adenylate cyclase and guanylate cyclase and mediates several cellular processes such as cell proliferation and cyclic nucleotide metabolism. The abnormal levels of calmodulin in the body will result in serious effects from metabolism to nerve growth and memory. Therefore, it is important to measure the calmodulin concentration in the body. In this work, we propose and experimentally demonstrate a plasmonic tilted fiber Bragg grating-based biosensor for calmodulin detection. The biosensor was made using an 18° tilted fiber Bragg grating with a 50 nm-thick gold nanofilm coating the surface of the fiber, and transient receptor potential channels were bonded onto the surface of the gold nanofilm to serve as bio-detectors for calmodulin detection. Experimental results showed that the limit of detection using our biosensor was 0.44 nM. Furthermore, we also demonstrated that the interaction between calmodulin and transient receptor potential channels was quite weak without calcium in the solution, which agrees with the biology. Our proposed biosensor has a simple structure, is easy to manufacture, and is of small size, making it a good choice for real-time, label-free, and microliter-volume biomolecule detection.
Factors Predicting Ictal Quality in Bilateral Electroconvulsive Therapy Sessions
Authors: de Arriba-Arnau Aida , Dalmau Llitjos Antonia , Soria Virginia , Savino Stelania , Salvat-Pujol Neus , Curto Jordi , Menchón José Manuel , Urretavizcaya Mikel
Published: June 2021

In electroconvulsive therapy (ECT), ictal characteristics predict treatment response and can be modified by changes in seizure threshold and in the ECT technique. We aimed to study the impact of ECT procedure-related variables that interact during each session and might influence the seizure results. Two hundred and fifty sessions of bilateral ECT in forty-seven subjects were included. Seizure results were evaluated by two different scales of combined ictal EEG parameters (seizure quality index (SQI) and seizure adequacy markers sum (SAMS) scores) and postictal suppression rating. Repeated measurement regression analyses were performed to identify predictors of each session’s three outcome variables. Univariate models identified age, physical status, hyperventilation, basal oxygen saturation, days between sessions, benzodiazepines, lithium, and tricyclic antidepressants as predictors of seizure quality. Days elapsed between sessions, higher oxygen saturation and protocolized hyperventilation application were significant predictors of better seizure quality in both scales used in multivariate models. Additionally, lower ASA classification influenced SQI scores as well as benzodiazepine use and lithium daily doses were predictors of SAMS scores. Higher muscle relaxant doses and lower applied stimulus intensities significantly influenced the postictal suppression rating. The study found several modifiable procedural factors that impacted the obtained seizure characteristics; they could be adjusted to optimize ECT session results.
Electrophysiological Evidence of Anticipatory Cognitive Control in the Stroop Task
Authors: Bianco Valentina , Berchicci Marika , Mussini Elena , Perri Rinaldo Livio , Quinzi Federico , Di Russo Francesco
Published: June 2021

The Stroop task has been largely used to explore the ability to inhibit the automatic process of reading when reporting the ink color of incongruent color-words. Given the extensive literature regarding the processes involved in task performance, here we aimed at exploring the anticipatory brain activities during the Stroop task using the event-related potential (ERP) method. To accomplish this, eighteen participants performed two different blocks where neutral words were intermixed with congruent and incongruent words, respectively. Results revealed consistent pre-stimulus activity over the frontal, premotor and parietal brain areas. The premotor and the parietal activities were also modulated by the Stroop effect, being more enhanced in the incongruent than in the congruent blocks. Present findings add on the current literature pointing at an unexplored locus of anticipatory cognitive control during task preparation, thus offering a new way to investigate top-down preparatory processes of performance control in the Stroop task.
DNA Methylation-Based Estimates of Circulating Leukocyte Composition for Predicting Colorectal Cancer Survival: A Prospective Cohort Study
Authors: Gào Xīn , Zhang Yan , Li Xiangwei , Jansen Lina , Alwers Elizabeth , Bewerunge-Hudler Melanie , Schick Matthias , Chang-Claude Jenny , Hoffmeister Michael , Brenner Hermann
Published: June 2021

Leukocytes are involved in the progression of colorectal cancer (CRC). The proportion of six major leukocyte subtypes can be estimated using epigenome-wide DNA methylation (DNAm) data from stored blood samples. Whether the composition of circulating leukocytes can be used as a prognostic factor is unclear. DNAm-based leukocyte proportions were obtained from a prospective cohort of 2206 CRC patients. Multivariate Cox regression models and survival curves were applied to assess associations between leukocyte composition and survival outcomes. A higher proportion of lymphocytes, including CD4+ T cells, CD8+ T cells, B cells, and NK cells, was associated with better survival, while a higher proportion of neutrophils was associated with poorer survival. CD4+ T cells outperformed other leukocytes in estimating the patients’ prognosis. Comparing the highest quantile to the lowest quantile of CD4+ T cells, hazard ratios (95% confidence intervals) of all-cause and CRC-specific mortality were 0.59 (0.48, 0.72) and 0.59 (0.45, 0.77), respectively. Furthermore, the association of CD4+ T cells and prognosis was stronger among patients with early or intermediate CRC or patients with colon cancer. In conclusion, the composition of circulating leukocytes estimated from DNAm, particularly the proportions of CD4+ T cells, could be used as promising independent predictors of CRC survival.
Newly Obtained Apple Pectin as an Adjunct to Irinotecan Therapy of Colorectal Cancer Reducing E. coli Adherence and β-Glucuronidase Activity
Authors: Palko-Łabuz Anna , Maksymowicz Jerzy , Sobieszczańska Beata , Wikiera Agnieszka , Skonieczna Magdalena , Wesołowska Olga , Środa-Pomianek Kamila
Published: June 2021

Colorectal cancer (CRC) is the second cause of cancer death worldwide. The composition and enzymatic activity of colonic microbiota can significantly affect the effectiveness of CRC chemotherapy. Irinotecan is a drug widely used to treat colon cancer. However, the transformation of a drug-glucuronide (SN-38G) back to its active form (SN-38) by bacterial β-glucuronidase (GUS) constitutes the primary reason for the observed intestinal toxicity of irinotecan. It was demonstrated that novel enzymatically extracted apple pectin (PC) might be a promising candidate for an adjunct to irinotecan therapy. PC itself reduced the viability of HCT 116 and Caco-2 colorectal cancer cells, induced apoptosis, and increased intracellular reactive oxygen species production. Moreover, PC enhanced the cytotoxic and proapoptotic effect of irinotecan (at concentrations below its IC50), i.e., synergistic effect was recorded. Additionally, PC exhibited potent anti-inflammatory properties and prevented adhesion of prototype adherent-invasive E. coli (AIEC) LF82 strain and laboratory K-12C600 strain to colon cancer cells. PC was also identified to be an effective inhibitor of bacterial GUS activity. Altogether, novel apple pectin was identified as a promising candidate for a supplement to irinotecan therapy that might alleviate its side-effects via inhibition of bacterial GUS and thus increasing its therapeutic efficacy.
PLEK2, RRM2, GCSH: A Novel WWOX-Dependent Biomarker Triad of Glioblastoma at the Crossroads of Cytoskeleton Reorganization and Metabolism Alterations
Authors: Kałuzińska Żaneta , Kołat Damian , Bednarek Andrzej K. , Płuciennik Elżbieta
Published: June 2021

Glioblastoma is one of the deadliest human cancers. Its malignancy depends on cytoskeleton reorganization, which is related to, e.g., epithelial-to-mesenchymal transition and metastasis. The malignant phenotype of glioblastoma is also affected by the WWOX gene, which is lost in nearly a quarter of gliomas. Although the role of WWOX in the cytoskeleton rearrangement has been found in neural progenitor cells, its function as a modulator of cytoskeleton in gliomas was not investigated. Therefore, this study aimed to investigate the role of WWOX and its collaborators in cytoskeleton dynamics of glioblastoma. Methodology on RNA-seq data integrated the use of databases, bioinformatics tools, web-based platforms, and machine learning algorithm, and the obtained results were validated through microarray data. PLEK2, RRM2, and GCSH were the most relevant WWOX-dependent genes that could serve as novel biomarkers. Other genes important in the context of cytoskeleton (BMP4, CCL11, CUX2, DUSP7, FAM92B, GRIN2B, HOXA1, HOXA10, KIF20A, NF2, SPOCK1, TTR, UHRF1, and WT1), metabolism (MTHFD2), or correlation with WWOX (COL3A1, KIF20A, RNF141, and RXRG) were also discovered. For the first time, we propose that changes in WWOX expression dictate a myriad of alterations that affect both glioblastoma cytoskeleton and metabolism, rendering new therapeutic possibilities.
Mitochondrial O-GlcNAc Transferase Interacts with and Modifies Many Proteins and Its Up-Regulation Affects Mitochondrial Function and Cellular Energy Homeostasis
Authors: Jóźwiak Paweł , Ciesielski Piotr , Zakrzewski Piotr K. , Kozal Karolina , Oracz Joanna , Budryn Grażyna , Żyżelewicz Dorota , Flament Stéphanie , Vercoutter-Edouart Anne-Sophie , Bray Fabrice , Lefebvre Tony , Krześlak Anna
Published: June 2021

O-GlcNAcylation is a cell glucose sensor. The addition of O-GlcNAc moieties to target protein is catalyzed by the O-Linked N-acetylglucosamine transferase (OGT). OGT is encoded by a single gene that yields differentially spliced OGT isoforms. One of them is targeted to mitochondria (mOGT). Although the impact of O-GlcNAcylation on cancer cells biology is well documented, mOGT’s role remains poorly investigated. We performed studies using breast cancer cells with up-regulated mOGT or its catalytic inactive mutant to identify proteins specifically modified by mOGT. Proteomic approaches included isolation of mOGT protein partners and O-GlcNAcylated proteins from mitochondria-enriched fraction followed by their analysis by mass spectrometry. Moreover, we analyzed the impact of mOGT dysregulation on mitochondrial activity and cellular metabolism using a variety of biochemical assays. We found that mitochondrial OGT expression is glucose-dependent. Elevated mOGT expression affected the mitochondrial transmembrane potential and increased intramitochondrial ROS generation. Moreover, mOGT up-regulation caused a decrease in cellular ATP level. We identified many mitochondrial proteins as mOGT substrates. Most of these proteins are localized in the mitochondrial matrix and the inner mitochondrial membrane and participate in mitochondrial respiration, fatty acid metabolism, transport, translation, apoptosis, and mtDNA processes. Our findings suggest that mOGT interacts with and modifies many mitochondrial proteins, and its dysregulation affects cellular bioenergetics and mitochondria function.
Severe Phenotype in Patients with Large Deletions of NF1
Authors: Pacot Laurence , Vidaud Dominique , Sabbagh Audrey , Laurendeau Ingrid , Briand-Suleau Audrey , Coustier Audrey , Maillard Théodora , Barbance Cécile , Morice-Picard Fanny , Sigaudy Sabine , Glazunova Olga , Damaj Lena , Layet Valérie , Quelin Chloé , Gilbert-Dussardier Brigitte , Audic Frédérique , Dollfus Hélène , Guerrot Anne-Marie , Lespinasse James , Julia Sophie , Vantyghem Marie-Christine , Drouard Magali , Lackmy Marilyn , Leheup Bruno , Alembik Yves , Lemaire Alexia , Nitschké Patrick , Petit Florence , Dieux Coeslier Anne , Mutez Eugénie , Taieb Alain , Fradin Mélanie , Capri Yline , Nasser Hala , Ruaud Lyse , Dauriat Benjamin , Bourthoumieu Sylvie , Geneviève David , Audebert-Bellanger Séverine , Nizon Mathilde , Stoeva Radka , Hickman Geoffroy , Nicolas Gaël , Mazereeuw-Hautier Juliette , Jannic Arnaud , Ferkal Salah , Parfait Béatrice , Vidaud Michel ,   members of the NF France Network, Wolkenstein Pierre , Pasmant Eric
Published: June 2021

Complete deletion of the NF1 gene is identified in 5–10% of patients with neurofibromatosis type 1 (NF1). Several studies have previously described particularly severe forms of the disease in NF1 patients with deletion of the NF1 locus, but comprehensive descriptions of large cohorts are still missing to fully characterize this contiguous gene syndrome. NF1-deleted patients were enrolled and phenotypically characterized with a standardized questionnaire between 2005 and 2020 from a large French NF1 cohort. Statistical analyses for main NF1-associated symptoms were performed versus an NF1 reference population. A deletion of the NF1 gene was detected in 4% (139/3479) of molecularly confirmed NF1 index cases. The median age of the group at clinical investigations was 21 years old. A comprehensive clinical assessment showed that 93% (116/126) of NF1-deleted patients fulfilled the NIH criteria for NF1. More than half had café-au-lait spots, skinfold freckling, Lisch nodules, neurofibromas, neurological abnormalities, and cognitive impairment or learning disabilities. Comparison with previously described “classic” NF1 cohorts showed a significantly higher proportion of symptomatic spinal neurofibromas, dysmorphism, learning disabilities, malignancies, and skeletal and cardiovascular abnormalities in the NF1-deleted group. We described the largest NF1-deleted cohort to date and clarified the more severe phenotype observed in these patients.
Inversion of the Photogalvanic Effect of Conductive Polymers by Porphyrin Dopants
Authors: Petrov Alexey A. , Lukyanov Daniil A. , Kopytko Oleg A. , Novoselova Julia V. , Alekseeva Elena V. , Levin Oleg V.
Published: June 2021

Conductive polymers are widely used as active and auxiliary materials for organic photovoltaic cells due to their easily tunable properties, high electronic conductivity, and light absorption. Several conductive polymers show the cathodic photogalvanic effect in pristine state. Recently, photoelectrochemical oxygen reduction has been demonstrated for nickel complexes of Salen-type ligands. Herein, we report an unexpected inversion of the photogalvanic effect caused by doping of the NiSalen polymers with anionic porphyrins. The observed effect was studied by means of UV-Vis spectroscopy, cyclic voltammetry and chopped light chronoamperometry. While pristine NiSalens exhibit cathodic photopolarization, doping with porphyrins inverts the polarization. As a result, photoelectrochemical oxidation of the ascorbate proceeds smoothly on the NiSalen electrode doped with zinc porphyrins. The highest photocurrents were observed on NiSalen polymer with o-phenylene imine bridge, doped with anionic zinc porphyrin. Assuming this, porphyrin serves both as a catalytic center for the oxidation of ascorbate and an internal electron donor, facilitating the photoinduced charge transport and anodic depolarization.
Studies of Nickel/Samarium-Doped Ceria for Catalytic Partial Oxidation of Methane and Effect of Oxygen Vacancy
Authors: Chien Andrew C. , Ye Nicole J. , Huang Chao-Wei , Tseng I-Hsiang
Published: June 2021

We investigated the performance of nickel/samarium-doped ceria (Ni/SDC) nanocatalysts on the catalytic partial oxidation of methane (CPOM). Studies of temperature-programmed surface reaction and reduction reveal that catalytic activity is determined by a synergistic effect produced by Ni metals and metal-support interaction. Catalytic activity was more dependent on the Ni content below 600 °C, while there is not much difference for all catalysts at high temperatures. The catalyst exhibiting high activities toward syngas production (i.e., a CH4 conversion >90% at 700 °C) requires a medium Ni-SDC interaction with an Sm/Ce ratio of about 1/9 to 2/8. This is accounted for by optimum oxygen vacancies and adequate ion diffusivity in the SDCs which, as reported, also display the highest ion conductivity for fuel cell applications.
Efficacy and Selectivity of FGF2-Saporin Cytosolically Delivered by PCI in Cells Overexpressing FGFR1
Authors: Vikan Aurora K. , Kostas Michal , Haugsten Ellen Margrethe , Selbo Pål K. , Wesche Jørgen
Published: June 2021

Fibroblast growth factor receptors (FGFRs) have become an attractive target in cancer research and therapy due to their implication in several cancers. Limitations of current treatment options require a need for additional, more specific and potent strategies to overcome cancers driven by FGFRs. Photochemical internalization (PCI) is a light-controlled method for cytosolic delivery of drugs that are entrapped in endosomes and lysosomes. We here evaluated the efficacy and selectivity of PCI of FGF2-saporin (FGF-SAP) in cells overexpressing FGFR1. FGF-SAP is a conjugate of FGF2 and the highly cytotoxic ribosome-inactivating protein (RIP) saporin, which is used as payload to eliminate cancer cells. Evaluation of the targeting effect of PCI of FGF-SAP was done by comparing the cytotoxic response in osteosarcoma cells with very low levels of FGFR1 (U2OS) to cells overexpressing FGFR1 (U2OS-R1). We demonstrate that PCI greatly enhances cytotoxicity of the drug showing efficient cell killing at pM concentrations of the drug in U2OS-R1 cells. However, U2OS cells were also sensitive to the toxin after PCI. Binding experiments using confocal microscopy and Western blotting techniques indicate that FGF-SAP is taken up by cells through heparan sulfate proteoglycans (HSPGs) in U2OS cells. We further show that the cytotoxicity of FGF-SAP in U2OS cells was reduced when cells were co-treated with heparin to compete out binding to HSPG, demonstrating that the cytotoxic effect was due to internalization by HSPGs. We conclude that to prevent off-target effects of FGF-based toxins, it will be necessary to circumvent binding to HSPGs, for example by mutating the binding site of FGF2 to HSPGs.
With-No-Lysine Kinase 1 (WNK1) Augments TRPV4 Function in the Aldosterone-Sensitive Distal Nephron
Authors: Tomilin Viktor N. , Pyrshev Kyrylo , Khayyat Naghmeh Hassanzadeh , Zaika Oleg , Pochynyuk Oleh
Published: June 2021

Kidneys play a central role in regulation of potassium homeostasis and maintenance of plasma K+ levels within a narrow physiological range. With-no-lysine (WNK) kinases, specifically WNK1 and WNK4, have been recognized to regulate K+ balance, in part, by orchestrating maxi K+ channel (BK)-dependent K+ secretion in the aldosterone-sensitive distal nephron (ASDN), which includes the connecting tubule and collecting duct. We recently demonstrated that the Ca2+-permeable TRPV4 channel is essential for BK activation in the ASDN. Furthermore, high K+ diet increases TRPV4 activity and expression largely in an aldosterone-dependent manner. In the current study, we aimed to test whether WNK kinases contribute to regulation of TRPV4 activity and its stimulation by aldosterone. Systemic inhibition of WNK with WNK463 (1 mg/kgBW for 3 days) markedly decreased TRPV4-dependent Ca2+ influx in freshly isolated split-opened collecting ducts. Aldosterone greatly increased TRPV4 activity and expression in cultured mpkCCDc14 cells and this effect was abolished in the presence of WNK463. Selective inhibition of WNK1 with WNK-in-11 (400 nM, 24 h) recapitulated the effects of WNK463 on TRPV4-dependent Ca2+ influx. Interestingly, WNK-in-11 did not interfere with up-regulation of TRPV4 expression by aldosterone, but prevented translocation of the channel to the apical plasma membrane. Furthermore, co-expression of TRPV4 and WNK1 into Chinese hamster ovary (CHO) cells increased the macroscopic TRPV4-dependent cation currents. In contrast, over-expression of TRPV4 with a dominant negative WNK1 variant (K233M) decreased the whole-cell currents, suggesting both stimulatory and permissive roles of WNK1 in regulation of TRPV4 activity. Overall, we show that WNK1 is essential for setting functional TRPV4 expression in the ASDN at the baseline and in response to aldosterone. We propose that this new mechanism contributes to regulation of K+ secretion and, by extension, urinary K+ levels to maintain systemic potassium homeostasis.
Transient Receptor Potential C 1/4/5 Is a Determinant of MTI-101 Induced Calcium Influx and Cell Death in Multiple Myeloma
Authors: Elzamzamy Osama M. , Johnson Brandon E. , Chen Wei-Chih , Hu Gangqing , Penner Reinhold , Hazlehurst Lori A.
Published: June 2021

Multiple myeloma (MM) is a currently incurable hematologic cancer. Patients that initially respond to therapeutic intervention eventually relapse with drug resistant disease. Thus, novel treatment strategies are critically needed to improve patient outcomes. Our group has developed a novel cyclic peptide referred to as MTI-101 for the treatment of MM. We previously reported that acquired resistance to HYD-1, the linear form of MTI-101, correlated with the repression of genes involved in store operated Ca2+ entry (SOCE): PLCβ, SERCA, ITPR3, and TRPC1 expression. In this study, we sought to determine the role of TRPC1 heteromers in mediating MTI-101 induced cationic flux. Our data indicate that, consistent with the activation of TRPC heteromers, MTI-101 treatment induced Ca2+ and Na+ influx. However, replacing extracellular Na+ with NMDG did not reduce MTI-101-induced cell death. In contrast, decreasing extracellular Ca2+ reduced both MTI-101-induced Ca2+ influx as well as cell death. The causative role of TRPC heteromers was established by suppressing STIM1, TRPC1, TRPC4, or TRPC5 function both pharmacologically and by siRNA, resulting in a reduction in MTI-101-induced Ca2+ influx. Mechanistically, MTI-101 treatment induces trafficking of TRPC1 to the membrane and co-immunoprecipitation studies indicate that MTI-101 treatment induces a TRPC1-STIM1 complex. Moreover, treatment with calpeptin inhibited MTI-101-induced Ca2+ influx and cell death, indicating a role of calpain in the mechanism of MTI-101-induced cytotoxicity. Finally, components of the SOCE pathway were found to be poor prognostic indicators among MM patients, suggesting that this pathway is attractive for the treatment of MM.
Phenotypic Characterization by Single-Cell Mass Cytometry of Human Intrahepatic and Peripheral NK Cells in Patients with Hepatocellular Carcinoma
Authors: Yoshida Yuichi , Yoshio Sachiyo , Yamazoe Taiji , Mori Taizo , Tsustui Yuriko , Kawai Hironari , Yoshikawa Shiori , Fukuhara Takasuke , Okamoto Toru , Ono Yoshihiro , Takahashi Yu , Hashida Ryuki , Kawaguchi Takumi , Taketomi Akinobu , Kanto Tatsuya
Published: June 2021

Overall response rates of systemic therapies against advanced hepatocellular carcinoma (HCC) remain unsatisfactory. Thus, searching for new immunotherapy targets is indispensable. NK cells are crucial effectors and regulators in the tumor microenvironment and a determinant of responsiveness to checkpoint inhibitors. We revealed the landscape of NK cell phenotypes in HCC patients to find potential immunotherapy targets. Using single cell mass cytometry, we analyzed 32 surface markers on CD56dim and CD56bright NK cells, which included Sialic acid-binding immunoglobulin-type lectins (Siglecs). We compared peripheral NK cells between HCC patients and healthy volunteers. We also compared NK cells, in terms of their localizations, on an individual patient bases between peripheral and intrahepatic NK cells from cancerous and noncancerous liver tissues. In the HCC patient periphery, CD160+CD56dim NK cells that expressed Siglec-7, NKp46, and NKp30 were reduced, while CD49a+CD56dim NK cells that expressed Siglec-10 were increased. CD160 and CD49a on CD56dim NK cells were significantly correlated to other NK-related markers in HCC patients, which suggested that CD160 and CD49a were signature molecules. CD49a+ CX3CR1+ Siglec-10+ NK cells had accumulated in HCC tissues. Considering further functional analyses, CD160, CD49a, CX3CR1, and Siglec-10 on CD56dim NK cells may be targets for immunotherapies of HCC patients.
Indium Ammoniates from Ammonothermal Synthesis: InAlF6(NH3)2, [In(NH3)6][AlF6], and [In2F(NH3)10]2[SiF6]5 ∙ 2 NH3
Authors: Becker Peter , Cekovski Toni Boris , Niewa Rainer
Published: June 2021

The ammonothermal synthesis of three ammoniates of indium, namely InAlF6(NH3)2, [In(NH3)6][AlF6], and [In2F(NH3)10]2[SiF6]5 ∙ 2 NH3 was successful from near-ammononeutral conditions in the presence of fluoride ions. Initially, all these compounds were obtained upon corrosion of the applied liner and crucible material Si3N4, which also contains small amounts of aluminum. The syntheses were performed in supercritical ammonia (T = 753 K, p up to 307 MPa). The crystal structures were solved and refined from single crystal X-ray diffraction intensity data. InAlF6(NH3)2 crystallizes as a typical layer-type structure with corner-sharing [InF4(NH3)2]– and [AlF6]3− octahedra. [In(NH3)6][AlF6] features isolated [In(NH3)6]3+ and [AlF6]3− octahedra. The crystal structure of [In2F(NH3)10]2[SiF6]5 ∙ 2 NH3 contains [(NH3)5In–F–In(NH3)5]5+ octahedra doubles next to [SiF6]2− octahedra and ammonia molecules. All intermediates have strong hydrogen bonding systems. The results from vibrational spectroscopy are reported.
Staging Investigations in Asymptomatic Early Breast Cancer Patients at the Cancer Centre of Southeastern Ontario
Authors: Kamel Dalia , Youssef Veronica , Hopman Wilma M. , Mates Mihaela
Published: June 2021

Background: In 2012, the American Society for Clinical Oncology (ASCO) identified five key opportunities in oncology to improve patient care, recommending against imaging tests for the staging of patients with early breast cancer (EBC) at low risk for metastases. Similarly, the European Society of Medical Oncology (ESMO) guideline does not support radiological staging in asymptomatic EBC (aEBC). The purpose of this study was to assess local practice and outcomes of staging investigations (SIs) in aEBC at the Cancer Centre of Southeastern Ontario (CCSEO). Methods: A retrospective electronic and paper chart review was undertaken to identify all aEBC patients treated at our institution between January 2012 and December 2014. Patients with pathological staging of T1-T2 and N0-1 with any receptor status were included. We collected patient demographics, treatment and pathologic tumor characteristics. The use and outcomes of initial and follow-up SIs were recorded. Data were analyzed to determine associations between the use of SIs and clinical characteristics (chi-square tests, independent samples t-tests and Mann–Whitney U tests). Results: From 2012 to 2014, 295 asymptomatic EBC patients were identified. The mean age was 64, 81% were postmenopausal and 76% had breast conserving surgery. Stage distribution was as follows: stage I 42%, stage IIA 37% and stage IIB 21%. Receptor status was as follows: ER+ 84%, HER2+ 13% and triple negative 12%. Adjuvant chemotherapy was received by 36%, Trastuzumab by 10% and endocrine therapy by 76% of patients. Baseline SIs were performed in 168 patients (57%) for a total of 332 tests. Overt metastatic disease was found in five patients (one bone scan and four CT scans). Seventy-one out of the 168 patients (42%) who received initial staging imaging underwent 138 follow-up imaging tests, none of which were diagnostic for metastases. Nine patients with suspicious CT findings underwent biopsies, of which four were malignant (one metastatic breast cancer and three new primaries). Factors significantly associated with SI were as follows: younger age (p = 0.001), premenopausal status (p = 0.01), T2 stage (p < 0.001), N1 stage (p < 0.001), HER2 positive (p < 0.001), triple negative status (p = 0.007) and use of adjuvant chemotherapy (p < 0.001). Conclusions: Over a 3-year period at our institution, more than 50% of aEBC patients underwent a total of 470 initial and follow-up staging tests, yielding a cancer diagnosis (metastatic breast cancer or second primary cancer) in four patients. We, therefore, conclude that routine-staging investigations in aEBC patients have low diagnostic value, supporting current guidelines that recommend against the routine use of SI in this population.
Identification of Diagnostic Biomarkers and Their Correlation with Immune Infiltration in Age-Related Macular Degeneration
Authors: Zeng Yuyang , Yin Xiujuan , Chen Changzheng , Xing Yiqiao
Published: June 2021

Age-related macular degeneration (AMD) is a progressive neurodegenerative disease of the central retina, with no suitable biomarkers for early diagnosis and treatment. This study aimed to find potential diagnostic biomarker candidates for AMD and investigate their immune-related roles in this pathology. Weight gene correlation analysis was first performed based on data from the Gene Expression Omnibus database and 20 hub genes were identified. The functional enrichment analyses showed that the innate immune response, inflammatory response, and complement activation were key pathways associated with AMD. Complement C1s (C1S), adrenomedullin (ADM), and immediate early response 5 like (IER5L) were identified as the crucial genes with favorable diagnostic values for AMD by using LASSO analysis and multiple logistic regression. Furthermore, a 3-gene model was constructed and proved to be of good diagnostic and predictive performance for AMD (AUC = 0.785, 0.840, and 0.810 in training, test, and validation set, respectively). Finally, CIBERSORT was used to evaluate the infiltration of immune cells in AMD tissues. The results showed that the NK cells, CD4 memory T cell activation, and macrophage polarization may be involved in the AMD process. C1S, ADM, and IER5L were correlated with the infiltration of the above immune cells. In conclusion, our study suggests that C1S, ADM, and IER5L are promising diagnostic biomarker candidates for AMD and may regulate the infiltration of immune cells in the occurrence and progression of AMD.
Active Herpes Zoster Mimicking Worsening of Axillary Lymph Node Metastases of Breast Cancer after Chemotherapy on 18F-Fluorodeoxyglucose Positron-Emission Tomography/Computed Tomography
Authors: Fujioka Tomoyuki , Yokoyama Kota , Mori Mio , Yashima Yuka , Yamaga Emi , Kubota Kazunori , Oyama Jun , Oda Goshi , Nakagawa Tsuyoshi , Tateishi Ukihide
Published: June 2021

A woman in her 60s presented to our hospital with a left breast mass that was diagnosed as breast cancer. 18F-Fluorodeoxyglucose positron-emission tomography/computed tomography (18F-FDG PET/CT) revealed intense, hot uptake in the cancerous mass and left axillary lymph node metastasis. After chemotherapy, another PET/CT scan was performed. Although the mass and left axillary lymph nodes shrank and FDG uptake decreased, enlarged lymph nodes with high FDG uptake appeared in the right axilla. The patient had a painful vesicular eruption on the front to the back of the right upper hemithorax, which was diagnosed as active herpes zoster. Active herpes zoster mimics a worsening axillary lymph node metastasis on the PET/CT scan.
A Positive Dermcidin Expression Is an Unfavorable Prognostic Marker for Extramammary Paget’s Disease
Authors: Ohmori Shun , Sawada Yu , Saito-Sasaki Natsuko , Sato Sayaka , Minokawa Yoko , Sugino Hitomi , Nanamori Hikaru , Yamamoto Kayo , Okada Etsuko , Nakamura Motonobu
Published: June 2021

Extramammary Paget’s disease is recognized as an apocrine-origin cutaneous tumor and is localized in the intraepithelial skin lesion. However, its advanced form is intractable, and there is currently no therapeutic option with a satisfactory level of clinical outcome. Therefore, it is of great importance to identify a potential biomarker to estimate tumor advancement in extramammary Paget’s disease. Dermcidin is an antimicrobial peptide derived from the eccrine gland and is identified as a biomarker in various malignancies. To investigate the potential of dermcidin in extramammary Paget’s disease, we investigated dermcidin expression in tumors using the immunostaining technique. Although previous studies have reported that extramammary Paget’s disease has no positive staining against dermcidin, 14 out of 60 patients showed positive staining of dermcidin in our study. To clarify the characteristics of positive dermcidin in extramammary Paget’s disease, we investigated the clinical characteristics of positive dermcidin extramammary Paget’s disease patients. Positive dermcidin patients showed a significantly high frequency of lymph node metastasis. We next investigated the impact of positive dermcidin on overall survival. Univariate analysis identified that positive dermcidin showed a significantly increased hazard ratio in overall survival, suggesting that dermcidin might be a prognostic factor for extramammary Paget’s disease.
Designing Bivariate Auto-Regressive Timeseries with Controlled Granger Causality
Authors: Hidaka Shohei , Torii Takuma
Published: June 2021

In this manuscript, we analyze a bivariate vector auto-regressive (VAR) model in order to draw the design principle of a timeseries with a controlled statistical inter-relationship. We show how to generate bivariate timeseries with given covariance and Granger causality (or, equivalently, transfer entropy), and show the trade-off relationship between these two types of statistical interaction. In principle, covariance and Granger causality are independently controllable, but the feasible ranges of their values which allow the VAR to be proper and have a stationary distribution are constrained by each other. Thus, our analysis identifies the essential tri-lemma structure among the stability and properness of VAR, the controllability of covariance, and that of Granger causality.
A Nonlinear Maximum Correntropy Information Filter for High-Dimensional Neural Decoding
Authors: Liu Xi , Chen Shuhang , Shen Xiang , Zhang Xiang , Wang Yiwen
Published: June 2021

Neural signal decoding is a critical technology in brain machine interface (BMI) to interpret movement intention from multi-neural activity collected from paralyzed patients. As a commonly-used decoding algorithm, the Kalman filter is often applied to derive the movement states from high-dimensional neural firing observation. However, its performance is limited and less effective for noisy nonlinear neural systems with high-dimensional measurements. In this paper, we propose a nonlinear maximum correntropy information filter, aiming at better state estimation in the filtering process for a noisy high-dimensional measurement system. We reconstruct the measurement model between the high-dimensional measurements and low-dimensional states using the neural network, and derive the state estimation using the correntropy criterion to cope with the non-Gaussian noise and eliminate large initial uncertainty. Moreover, analyses of convergence and robustness are given. The effectiveness of the proposed algorithm is evaluated by applying it on multiple segments of neural spiking data from two rats to interpret the movement states when the subjects perform a two-lever discrimination task. Our results demonstrate better and more robust state estimation performance when compared with other filters.
Quantum Advantages of Communication Complexity from Bell Nonlocality
Authors: Jia Zhih-Ahn , Wei Lu , Wu Yu-Chun , Guo Guang-Can
Published: June 2021

Communication games are crucial tools for investigating the limitations of physical theories. The communication complexity (CC) problem is a typical example, for which several distributed parties attempt to jointly calculate a given function with limited classical communications. In this work, we present a method to construct CC problems from Bell tests in a graph-theoretic way. Starting from an experimental compatibility graph and the corresponding Bell test function, a target function that encodes the information of each edge can be constructed; then, using this target function, we can construct a CC function, and by pre-sharing entangled states, its success probability exceeds that of the arbitrary classical strategy. The non-signaling protocol based on the Popescu–Rohrlich box is also discussed, and the success probability in this case reaches one.
Approaching Bounded Rationality: From Quantum Probability to Criticality
Authors: Tonello Lucio , Grigolini Paolo
Published: June 2021

The bounded rationality mainstream is based on interesting experiments showing human behaviors violating classical probability (CP) laws. Quantum probability (QP) has been shown to successfully figure out such issues, supporting the hypothesis that quantum mechanics is the central fundamental pillar for brain function and cognition emergence. We discuss the decision-making model (DMM), a paradigmatic instance of criticality, which deals with bounded rationality issues in a similar way as QP, generating choices that cannot be accounted by CP. We define this approach as criticality-induced bounded rationality (CIBR). For some aspects, CIBR is even more satisfactory than QP. Our work may contribute to considering criticality as another possible fundamental pillar in order to improve the understanding of cognition and of quantum mechanics as well.
Retinex-Based Fast Algorithm for Low-Light Image Enhancement
Authors: Liu Shouxin , Long Wei , He Lei , Li Yanyan , Ding Wei
Published: June 2021

We proposed the Retinex-based fast algorithm (RBFA) to achieve low-light image enhancement in this paper, which can restore information that is covered by low illuminance. The proposed algorithm consists of the following parts. Firstly, we convert the low-light image from the RGB (red, green, blue) color space to the HSV (hue, saturation, value) color space and use the linear function to stretch the original gray level dynamic range of the V component. Then, we estimate the illumination image via adaptive gamma correction and use the Retinex model to achieve the brightness enhancement. After that, we further stretch the gray level dynamic range to avoid low image contrast. Finally, we design another mapping function to achieve color saturation correction and convert the enhanced image from the HSV color space to the RGB color space after which we can obtain the clear image. The experimental results show that the enhanced images with the proposed method have better qualitative and quantitative evaluations and lower computational complexity than other state-of-the-art methods.
Donut-Shaped mmWave Printed Antenna Array for 5G Technology
Authors: Kamal Mian Muhammad , Yang Shouyi , Kiani Saad Hassan , Anjum Muhammad Rizwan , Alibakhshikenari Mohammad , Arain Zulfiqar Ali , Jamali Abdul Aleem , Lalbakhsh Ali , Limiti Ernesto
Published: June 2021

This article presents compact and novel shape ring slotted antenna array operating at mmWave band on central frequency of 28 GHz. The proposed structure designed at 0.256 mm thin Roggers 5880 is composed of a ring shape patch with a square slot etched at the top mid-section of partial ground plane. Through optimizing the ring and square slot parameters high bandwidth of 8 GHz is achieved ranging from 26 to 32 GHz with simulated gain of 3.95 dBi and total efficiency of 96% for single element. The proposed structure is further transformed in a 4 element linear array manner. With compact dimensions of 20 mm × 22 mm for array, the proposed antenna delivers high simulated gain of 10.7 dBi and is designed in such a way that it exhibits dual beam response over the entire band of interest and simulated results well agree with fabricated prototype measurements.
Condition-Based Maintenance of HVAC on a High-Speed Train for Fault Detection
Authors: Ciani Lorenzo , Guidi Giulia , Patrizi Gabriele , Galar Diego
Published: June 2021

Reliability-centered maintenance (RCM) is a well-established method for preventive maintenance planning. This paper focuses on the optimization of a maintenance plan for an HVAC (heating, ventilation and air conditioning) system located on high-speed trains. The first steps of the RCM procedure help in identifying the most critical items of the system in terms of safety and availability by means of a failure modes and effects analysis. Then, RMC proposes the optimal maintenance tasks for each item making up the system. However, the decision-making diagram that leads to the maintenance choice is extremely generic, with a consequent high subjectivity in the task selection. This paper proposes a new fuzzy-based decision-making diagram to minimize the subjectivity of the task choice and preserve the cost-efficiency of the procedure. It uses a case from the railway industry to illustrate the suggested approach, but the procedure could be easily applied to different industrial and technological fields. The results of the proposed fuzzy approach highlight the importance of an accurate diagnostics (with an overall 86% of the task as diagnostic-based maintenance) and condition monitoring strategy (covering 54% of the tasks) to optimize the maintenance plan and to minimize the system availability. The findings show that the framework strongly mitigates the issues related to the classical RCM procedure, notably the high subjectivity of experts. It lays the groundwork for a general fuzzy-based reliability-centered maintenance method.
Metal-Insulator-Metal Waveguide-Based Racetrack Integrated Circular Cavity for Refractive Index Sensing Application
Authors: Butt Muhammad A. , Kaźmierczak Andrzej , Kazanskiy Nikolay L. , Khonina Svetlana N.
Published: June 2021

Herein, a novel cavity design of racetrack integrated circular cavity established on metal-insulator-metal (MIM) waveguide is suggested for refractive index sensing application. Over the past few years, we have witnessed several unique cavity designs to improve the sensing performance of the plasmonic sensors created on the MIM waveguide. The optimized cavity design can provide the best sensing performance. In this work, we have numerically analyzed the device design by utilizing the finite element method (FEM). The small variations in the geometric parameter of the device can bring a significant shift in the sensitivity and the figure of merit (FOM) of the device. The best sensitivity and FOM of the anticipated device are 1400 nm/RIU and ~12.01, respectively. We believe that the sensor design analyzed in this work can be utilized in the on-chip detection of biochemical analytes.
Wearable Airbag System for Real-Time Bicycle Rider Accident Recognition by Orthogonal Convolutional Neural Network (O-CNN) Model
Authors: Woo Joo , Jo So-Hyeon , Byun Gi-Sig , Kwon Baek-Soon , Jeong Jae-Hoon
Published: June 2021

As demand for bicycles increases, bicycle-related accidents are on the rise. There are many items such as helmets and racing suits for bicycles, but many people do not wear helmets even if they are the most basic safety protection. To protect the rider from accidents, technology is needed to measure the rider’s motion condition in real time, determine whether an accident has occurred, and cope with the accident. This paper describes an artificial intelligence airbag. The artificial intelligence airbag is a system that measures real-time motion conditions of a bicycle rider using a six-axis sensor and judges accidents with artificial intelligence to prevent neck injuries. The MPU 6050 is used to understand changes in the rider’s movement in normal and accident conditions. The angle is determined by using the measured data and artificial intelligence to determine whether an accident happened or not by analyzing acceleration and angle. In this paper, similar methods of artificial intelligence (NN, PNN, CNN, PNN-CNN) to are compared to the orthogonal convolutional neural network (O-CNN) method in terms of the performance of judgment accuracy for accident situations. The artificial neural networks were applied to the airbag system and verified the reliability and judgment in advance.
Analysis and Performance Assessment of a Real-Time Correction Pseudo-Correlation Microwave Radiometer for Medical Applications
Authors: Villa Enrique , Aja Beatriz , de la Fuente Luisa , Artal Eduardo , Arteaga-Marrero Natalia , González-Pérez Sara , Ruiz-Alzola Juan
Published: June 2021

A new configuration of a pseudo-correlation type radiometer is proposed for a microwave biomedical application, such as diabetic foot neuropathy. The new approach as well as its simulated performance are thoroughly assessed using commercial off-the-shelf components and custom designed subsystems. We configured a pseudo-correlation receiver, centred at 3.5 GHz, to validate the proposal, comparing its simulated response with a measured alternative based on a 90∘ hybrid coupler pseudo-correlation prototype. We custom designed a balanced Wilkinson power divider and a 180∘ hybrid coupler to fulfil the receiver’s requirements. The proposed configuration demonstrated an improved noise temperature response. The main advantage is to enable the recalibration of the receiver through simultaneous measurable output signals, proportional to each input signal, as well as the correlated response between them.
Communication-Induced Checkpointing with Message Logging beyond the Piecewise Deterministic (PWD) Model for Distributed Systems
Authors: Ahn Jinho
Published: June 2021

This paper introduces an effective communication-induced checkpointing protocol using message logging to enable the number of extra checkpoints to be far lower than the previous number. Even if a situation occurs in which it is decided that a process receiving a message has to perform forced checkpointing, our protocol allows the process to skip the forced checkpointing action if it recognizes that the state of its sender right before the receipt of the message is recoverable. Additionally, the communication-induced checkpointing protocol is thus not required to assume the piecewise deterministic model, despite being combined with message logging. This protocol can maintain these features by piggybacking a one-bit variable and an n-size vector on each message sent. Our simulation results verify our claim that the presented protocol performs much better than the representative optimized protocol with respect to the forced checkpointing frequency, regardless of the communication pattern.