bluuebunny/crossref_metadata_2025 huggingface dataset:
A Configurable Dependency Model of a SCADA System for Goal-Oriented Risk Assessment
Authors: Cherdantseva Yulia , Burnap Pete , Nadjm-Tehrani Simin , Jones Kevin
Published: May 2022

A key purpose of a Supervisory Control and Data Acquisition (SCADA) system is to enable either an on-site or remote supervisory control and monitoring of physical processes of various natures. In order for a SCADA system to operate safely and securely, a wide range of experts with diverse backgrounds must work in close rapport. It is critical to have an overall view of an entire system at a high level of abstraction which is accessible to all experts involved, and which assists with gauging and assessing risks to the system. Furthermore, a SCADA system is composed of a large number of interconnected technical and non-technical sub-elements, and it is crucial to capture the dependencies between these sub-elements for a comprehensive and rigorous risk assessment. In this paper, we present a generic configurable dependency model of a SCADA system which captures complex dependencies within a system and facilitates goal-oriented risk assessment. The model was developed by collecting and analysing the understanding of the dependencies within a SCADA system from 36 domain experts. We describe a methodology followed for developing the dependency model, present an illustrative example where the generic dependency model is configured for a SCADA system controlling water distribution, and outline an exemplary risk assessment process based on it.
Advanced ML-Based Ensemble and Deep Learning Models for Short-Term Load Forecasting: Comparative Analysis Using Feature Engineering
Authors: Phyo Pyae-Pyae , Jeenanunta Chawalit
Published: May 2022

Short-term load forecasting (STLF) plays a pivotal role in the electricity industry because it helps reduce, generate, and operate costs by balancing supply and demand. Recently, the challenge in STLF has been the load variation that occurs in each period, day, and seasonality. This work proposes the bagging ensemble combining two machine learning (ML) models—linear regression (LR) and support vector regression (SVR). For comparative analysis, the performance of the proposed model is evaluated and compared with three advanced deep learning (DL) models, namely, the deep neural network (DNN), long short-term memory (LSTM), and hybrid convolutional neural network (CNN)+LSTM models. These models are trained and tested on the data collected from the Electricity Generating Authority of Thailand (EGAT) with four different input features. The forecasting performance is measured considering mean absolute percentage error (MAPE), mean absolute error (MAE), and mean squared error (MSE) parameters. Using several input features, experimental results show that the integrated model provides better accuracy than others. Therefore, it can be revealed that our approach could improve accuracy using different data in different forecasting fields.
Development Trends of Production Systems through the Integration of Lean Management and Industry 4.0
Authors: Florescu Adriana , Barabas Sorin
Published: May 2022

The integration of efficient production and management systems with the new Industry 4.0 concept represents a challenge for any company wishing to adapt its processes in order to increase performance, both at the operational and the organizational levels, through digitization and connectivity. This research proposes an analysis of Lean tools and Industry 4.0 technologies for compatibility in order to provide a framework model for development and integration in industrial applications. Through a systematic review of the literature, this paper contributes to the development of the current vision regarding the implementation and integration of the two “paradigms” of production. An analysis of the current key production strategies was performed through a new conceptual approach from the perspective of correlating the Lean management system, a system that has been stable in recent decades, with the innovative technologies of Industry 4.0. The applicative character of the research consisted of the optimization by simulation of a flexible production system in which the two concepts were integrated. The results showed that the implementation of Lean in the field of flexible manufacturing, correlated with the integration of Industry 4.0 techniques, such as digital twin and simulation, led to improved production processes by fast and flexible reconfiguration, with the two concepts being interdependent.
An Investigation of the Effects and Consequences of Combining Expanding Dual Pin with Radial Spherical Plain Bearings
Authors: Karlsen Øyvind , Lemu Hirpa G. , Berkani Imad
Published: May 2022

An expanding pin locks the pin assembly to its supports and bearings and prevents any relative movements between the surfaces in contact. In this study, the diameter changes of the bearing inner ring as a function of the expanding pin’s tightening torque were studied. In addition, the required rotational moment of a set of complete bearings locked to an expanding pin solution was studied by exposing the assembly to a combination of an increasing radially outwards directed load from the bolt torquing and a radially external inwards directed load from a hydraulic jack. The bearings were of type Radial Spherical Plain Bearings (RSPBs), GE 80 ES, steel/steel, and loaded externally up to their maximum dynamic limit of 400 kN. The results indicate a major reduction in the required rotation moment of the bearing when the bearing inner ring is expanded by use of an expanding pin. The reduction of rotation moment indicates reduced contact pressure and friction force between the two bearing rings, which ultimately can have a reduced effect on ring surface wear and a positive effect on the bearing operational lifetime.
From Lugano to Krakow: The Career of Giovanni Battista Trevano as a Royal Architect at the Vasa Court in the Polish–Lithuanian Commonwealth
Authors: Janowski Piotr Józef
Published: May 2022

Throughout the 16th and 17th centuries, many builders, artists, and architects living on the shores of Italian lakes decided to settle in Poland. Upon arrival, they pursued brilliant careers in various areas of life. Over time, they became Polonized. This was also the case for Giovanni Battista Trevano, who was active in Krakow in the first half of the 17th century and whose lifetime achievement was to become the royal architect of the Vasa kings. This article presents Trevano’s artistic oeuvre and provides insight into his social, economic, and intellectual status in the new community, including the architect’s offspring, who pursued successful careers in army, church, and state offices throughout the 17th and 18th centuries. These new findings are based on manuscripts that have recently been discovered by the author of the article in both Polish and Swiss archives. They allow for expanding the knowledge of the Trevano family’s genealogy and biography, and correcting some unjustified views in the discourse. On the basis of research on new archival sources, one can conclude that Giovanni Battista Trevano was a prominent architect, who is credited with introducing in Poland the early Baroque style, which soon became dominant in northern European art.
Intercomparison of Vaisala RS92 and RS41 Radiosonde Temperature Sensors under Controlled Laboratory Conditions
Authors: Rosoldi Marco , Coppa Graziano , Merlone Andrea , Musacchio Chiara , Madonna Fabio
Published: May 2022

Radiosoundings are essential for weather and climate applications, as well as for calibration and validation of remote sensing observations. Vaisala RS92 radiosondes have been widely used on a global scale until 2016; although in the fall of 2013, Vaisala introduced the RS41 model to progressively replace the RS92. To ensure the highest quality and homogeneity of measurements following the transition from RS92 to RS41, intercomparisons of the two radiosonde models are needed. A methodology was introduced to simultaneously test and compare the two radiosonde models inside climatic chambers, in terms of noise, calibration accuracy, and bias in temperature measurements. A pair of RS41 and RS92 radiosondes has been tested at ambient pressure under very different temperature and humidity conditions, reproducing the atmospheric conditions that a radiosonde can meet at the ground before launch. The radiosondes have also been tested before and after fast (within ≈ 10 s) temperature changes of about ±20 °C, simulating a scenario similar to steep thermal changes that radiosondes can meet when passing from indoor to outdoor environment during the pre-launch phase. The results show that the temperature sensor of RS41 is less affected by noise and more accurate than that of RS92, with noise values less than 0.06 °C for RS41 and less than 0.1 °C for RS92. The deviation from the reference value, referred to as calibration error, is within ±0.1 °C for RS41 and the related uncertainty (hereafter with coverage factor k = 1) is less than 0.06 °C, while RS92 is affected by a cold bias in the calibration, which ranges from 0.1 °C up to a few tenths of a degree, with a calibration uncertainty less than 0.1 °C. The temperature bias between RS41 and RS92 is within ±0.1 °C, while its uncertainty is less than 0.1 °C. The fast and steep thermal changes that radiosondes can meet during the pre-launch phase might lead to a noise increase in temperature sensors during radiosoundings, up to 0.1 °C for RS41 and up to 0.3 °C for RS92, with a similar increase in their calibration uncertainty, as well as an increase in the uncertainty of their bias up to 0.3 °C.
Preconditioning Methods to Improve Mesenchymal Stromal Cell-Derived Extracellular Vesicles in Bone Regeneration—A Systematic Review
Authors: Hertel Fernanda Campos , Silva Aline Silvestrini da , Sabino Adriano de Paula , Valente Fabrício Luciani , Reis Emily Correna Carlo
Published: May 2022

Mesenchymal stromal cells (MSCs) have long been used in research for bone regeneration, with evidence of their beneficial properties. In the segmental area of MSC-based therapies, MSC-derived extracellular vesicles (EVs) have also shown great therapeutic effects in several diseases, including bone healing. This study aimed to assess whether the conditioning of MSCs improves the therapeutic effects of their derived extracellular vesicles for bone regeneration. Electronic research was performed until February 2021 to recover the studies in the following databases: PubMed, Scopus, and Web of Science. The studies were screened based on the inclusion criteria. Relevant information was extracted, including in vitro and in vivo experiments, and the animal studies were evaluated for risk of bias by the SYRCLE tool. A total of 463 studies were retrieved, and 18 studies met the inclusion criteria (10 studies for their in vitro analysis, and 8 studies for their in vitro and in vivo analysis). The conditioning methods reported included: osteogenic medium; dimethyloxalylglycine; dexamethasone; strontium-substituted calcium silicate; hypoxia; 3D mechanical microenvironment; and the overexpression of miR-375, bone morphogenetic protein-2, and mutant hypoxia-inducible factor-1α. The conditioning methods of MSCs in the reported studies generate exosomes able to significantly promote bone regeneration. However, heterogeneity regarding cell source, conditioning method, EV isolation and concentration, and defect model was observed among the studies. The different conditioning methods reported in this review do improve the therapeutic effects of MSC-derived EVs for bone regeneration, but they still need to be addressed in larger animal models for further clinical application.
Chronic Supplementation of 2S-Hesperidin Improves Acid-Base Status and Decreases Lactate at FatMax, at Ventilatory Threshold 1 and 2 and after an Incremental Test in Amateur Cyclists
Authors: Martínez-Noguera Francisco Javier , Alcaraz Pedro E. , Carlos-Vivas Jorge , Marín-Pagán Cristian
Published: May 2022

Chronic supplementation with 2S-hesperidin improves performance; however, the mechanisms underlying this effect have not yet been explored. Therefore, the aim of this study was to assess whether changes in acid-base status may be associated with improved performance after 2S-hesperidin supplementation compared to microcellulose (placebo). Forty amateur cyclists (n = 20 per group) underwent a rectangular test where capillary blood samples were taken at baseline, FatMax1, VT1, VT2, PMAX, FatMax2 and EPOC to measure acid-base parameters. After eight weeks of 2S-hesperidin supplementation (500 mg/d) increased HCO3−, SBC, ABE (p ≤ 0.05) and decreased Lac were found at FatMax1, VT1, FatMax2 and EPOC (p ≤ 0.05), while decreased Lac at VT2 was found with a large effect size (ES = 1.15) compared to placebo. Significant group differences in the area under the curve were observed when comparing pre-post-intervention pH changes (p = 0.02) between groups. Chronic supplementation with 2S-hesperidin improved acid-base status and Lac, both at low-moderate and submaximal intensities, improving recovery after exercise-to-exhaustion in amateur cyclists.
Randomizing of Oligopeptide Conformations by Nearest Neighbor Interactions between Amino Acid Residues
Authors: Schweitzer-Stenner Reinhard , Milorey Bridget , Schwalbe Harald
Published: May 2022

Flory’s random coil model assumes that conformational fluctuations of amino acid residues in unfolded poly(oligo)peptides and proteins are uncorrelated (isolated pair hypothesis, IPH). This implies that conformational energies, entropies and solvation free energies are all additive. Nearly 25 years ago, analyses of coil libraries cast some doubt on this notion, in that they revealed that aromatic, but also β-branched side chains, could change the 3J(HNHCα) coupling of their neighbors. Since then, multiple bioinformatical, computational and experimental studies have revealed that conformational propensities of amino acids in unfolded peptides and proteins depend on their nearest neighbors. We used recently reported and newly obtained Ramachandran plots of tetra- and pentapeptides with non-terminal homo- and heterosequences of amino acid residues to quantitatively determine nearest neighbor coupling between them with a Ising type model. Results reveal that, depending on the choice of amino acid residue pairs, nearest neighbor interactions either stabilize or destabilize pairs of polyproline II and β-strand conformations. This leads to a redistribution of population between these conformations and a reduction in conformational entropy. Interactions between residues in polyproline II and turn(helix)-forming conformations seem to be cooperative in most cases, but the respective interaction parameters are subject to large statistical errors.
Kinases on Double Duty: A Review of UniProtKB Annotated Bifunctionality within the Kinome
Authors: Rangwala Aziz M. , Mingione Victoria R. , Georghiou George , Seeliger Markus A.
Published: May 2022

Phosphorylation facilitates the regulation of all fundamental biological processes, which has triggered extensive research of protein kinases and their roles in human health and disease. In addition to their phosphotransferase activity, certain kinases have evolved to adopt additional catalytic functions, while others have completely lost all catalytic activity. We searched the Universal Protein Resource Knowledgebase (UniProtKB) database for bifunctional protein kinases and focused on kinases that are critical for bacterial and human cellular homeostasis. These kinases engage in diverse functional roles, ranging from environmental sensing and metabolic regulation to immune-host defense and cell cycle control. Herein, we describe their dual catalytic activities and how they contribute to disease pathogenesis.
miRNA Pattern in Hypoxic Microenvironment of Kidney Cancer—Role of PTEN
Authors: Majewska Aleksandra , Brodaczewska Klaudia , Filipiak-Duliban Aleksandra , Kajdasz Arkadiusz , Kieda Claudine
Published: May 2022

MicroRNAs are post-transcriptional regulators of gene expression, and disturbances of their expression are the basis of many pathological states, including cancers. The miRNA pattern in the context of tumor microenvironment explains mechanisms related to cancer progression and provides a potential target of modern therapies. Here we show the miRNA pattern in renal cancer focusing on hypoxia as a characteristic feature of the tumor microenvironment and dysregulation of PTEN, being a major tumor suppressor. Methods comprised the CRSPR/Cas9 mediated PTEN knockout in the Renca kidney cancer cell line and global miRNA expression analysis in both in vivo and in vitro (in normoxic and hypoxic conditions). The results were validated on human cancer models with distinct PTEN status. The increase in miR-210-3p in hypoxia was universal; however, the hypoxia-induced decrease in PTEN was associated with an increase in miR-221-3p, the loss of PTEN affected the response to hypoxia differently by decreasing miR-10b-5p and increasing miR-206-3p. In turn, the complete loss of PTEN induces miR-155-5p, miR-100-5p. Upregulation of miR-342-3p in knockout PTEN occurred in the context of the whole tumor microenvironment. Thus, effective identification of miRNA patterns in cancers must consider the specificity of the tumor microenvironment together with the mutations of key suppressors.
Production of New Microbially Conjugated Bile Acids by Human Gut Microbiota
Authors: Garcia Carlos J. , Kosek Vit , Beltrán David , Tomás-Barberán Francisco A. , Hajslova Jana
Published: May 2022

Gut microbes have been recognized to convert human bile acids by deconjugation, dehydroxylation, dehydrogenation, and epimerization of the cholesterol core, but the ability to re-conjugate them with amino acids as an additional conversion has been recently described. These new bile acids are known as microbially conjugated bile acids (MCBAs). The aim of this study was to evaluate the MCBAs diversity produced by the gut microbiota through a metabolomics approach. In this study, fresh fecal samples from healthy donors were evaluated to explore the re-conjugation of chenodeoxycholic and 3-oxo-chenodeoxycholic acids by the human gut microbiota. No significant differences were found between the conversion trend of both BAs incubations. The in vitro results showed a clear trend to first accumulate the epimer isoursochenodeoxycholic acid and the dehydroxylated lithocholic acid derivatives in samples incubated with chenodeoxycholic and 3-oxo-chenodeoxycholic acid. They also showed a strong trend for the production of microbially conjugated dehydroxylated bile acids instead of chenodeoxycholic backbone conjugates. Different molecules and isomers of MCBAs were identified, and the new ones, valolithocholate ester and leucolithocholate ester, were identified and confirmed by MS/MS. These results document the gut microbiota’s capability to produce esters of MCBAs on hydroxyls of the sterol backbone in addition to amides at the C24 acyl site. This study opens a new perspective to study the BAs diversity produced by the human gut microbiota.
Comparative Transcriptome Analysis of Agrobacterium tumefaciens Reveals the Molecular Basis for the Recalcitrant Genetic Transformation of Camellia sinensis L.
Authors: Jin Ke , Tian Na , da Silva Ferreira Jorge Freire , Sandhu Devinder , Xiao Lizheng , Gu Meiyi , Luo Yiping , Zhang Xiangqin , Liu Guizhi , Liu Zhonghua , Huang Jianan , Liu Shuoqian
Published: May 2022

Tea (Camellia sinensis L.), an important economic crop, is recalcitrant to Agrobacterium-mediated transformation (AMT), which has seriously hindered the progress of molecular research on this species. The mechanisms leading to low efficiency of AMT in tea plants, related to the morphology, growth, and gene expression of Agrobacterium tumefaciens during tea-leaf explant infection, were compared to AMT of Nicotiana benthamiana leaves in the present work. Scanning electron microscopy (SEM) images showed that tea leaves induced significant morphological aberrations on bacterial cells and affected pathogen–plant attachment, the initial step of a successful AMT. RNA sequencing and transcriptomic analysis on Agrobacterium at 0, 3 and 4 days after leaf post-inoculation resulted in 762, 1923 and 1656 differentially expressed genes (DEGs) between the tea group and the tobacco group, respectively. The expressions of genes involved in bacterial fundamental metabolic processes, ATP-binding cassette (ABC) transporters, two-component systems (TCSs), secretion systems, and quorum sensing (QS) systems were severely affected in response to the tea-leaf phylloplane. Collectively, these results suggest that compounds in tea leaves, especially gamma-aminobutyrate (GABA) and catechins, interfered with plant–pathogen attachment, essential minerals (iron and potassium) acquisition, and quorum quenching (QQ) induction, which may have been major contributing factors to hinder AMT efficiency of the tea plant.
Flavonoid Biosynthesis Genes in Triticum aestivum L.: Methylation Patterns in Cis-Regulatory Regions of the Duplicated CHI and F3H Genes
Authors: Strygina Ksenia , Khlestkina Elena
Published: May 2022

Flavonoids are a diverse group of secondary plant metabolites that play an important role in the regulation of plant development and protection against stressors. The biosynthesis of flavonoids occurs through the activity of several enzymes, including chalcone isomerase (CHI) and flavanone 3-hydroxylase (F3H). A functional divergence between some copies of the structural TaCHI and TaF3H genes was previously shown in the allohexaploid bread wheat Triticum aestivum L. (BBAADD genome). We hypothesized that the specific nature of TaCHI and TaF3H expression may be induced by the methylation of the promoter. It was found that the predicted position of CpG islands in the promoter regions of the analyzed genes and the actual location of methylation sites did not match. We found for the first time that differences in the methylation status could affect the expression of TaCHI copies, but not the expression of TaF3Hs. At the same time, we revealed significant differences in the structure of the promoters of only the TaF3H genes, while the TaCHI promoters were highly homologous. We assume that the promoter structure in TaF3Hs primarily affects the change in the nature of gene expression. The data obtained are important for understanding the mechanisms that regulate the synthesis of flavonoids in allopolyploid wheat and show that differences in the structure of promoters have a key effect on gene expression.
Immune-Related Protein Interaction Network in Severe COVID-19 Patients toward the Identification of Key Proteins and Drug Repurposing
Authors: Sagulkoo Pakorn , Suratanee Apichat , Plaimas Kitiporn
Published: May 2022

Coronavirus disease 2019 (COVID-19) is still an active global public health issue. Although vaccines and therapeutic options are available, some patients experience severe conditions and need critical care support. Hence, identifying key genes or proteins involved in immune-related severe COVID-19 is necessary to find or develop the targeted therapies. This study proposed a novel construction of an immune-related protein interaction network (IPIN) in severe cases with the use of a network diffusion technique on a human interactome network and transcriptomic data. Enrichment analysis revealed that the IPIN was mainly associated with antiviral, innate immune, apoptosis, cell division, and cell cycle regulation signaling pathways. Twenty-three proteins were identified as key proteins to find associated drugs. Finally, poly (I:C), mitomycin C, decitabine, gemcitabine, hydroxyurea, tamoxifen, and curcumin were the potential drugs interacting with the key proteins to heal severe COVID-19. In conclusion, IPIN can be a good representative network for the immune system that integrates the protein interaction network and transcriptomic data. Thus, the key proteins and target drugs in IPIN help to find a new treatment with the use of existing drugs to treat the disease apart from vaccination and conventional antiviral therapy.
Biomarker Characterization and Prediction of Virulence and Antibiotic Resistance from Helicobacter pylori Next Generation Sequencing Data
Authors: Vital Joana S. , Tanoeiro Luís , Lopes-Oliveira Ricardo , Vale Filipa F.
Published: May 2022

The Gram-negative bacterium Helicobacter pylori colonizes c.a. 50% of human stomachs worldwide and is the major risk factor for gastric adenocarcinoma. Its high genetic variability makes it difficult to identify biomarkers of early stages of infection that can reliably predict its outcome. Moreover, the increasing antibiotic resistance found in H. pylori defies therapy, constituting a major human health problem. Here, we review H. pylori virulence factors and genes involved in antibiotic resistance, as well as the technologies currently used for their detection. Furthermore, we show that next generation sequencing may lead to faster characterization of virulence factors and prediction of the antibiotic resistance profile, thus contributing to personalized treatment and management of H. pylori-associated infections. With this new approach, more and permanent data will be generated at a lower cost, opening the future to new applications for H. pylori biomarker identification and antibiotic resistance prediction.
Vascularization of Patient-Derived Tumoroid from Non-Small-Cell Lung Cancer and Its Microenvironment
Authors: Seitlinger Joseph , Nounsi Anasse , Idoux-Gillet Ysia , Santos Pujol Eloy , Lê Hélène , Grandgirard Erwan , Olland Anne , Lindner Véronique , Zaupa Cécile , Balloul Jean-Marc , Quemeneur Eric , Massard Gilbert , Falcoz Pierre-Emmanuel , Hua Guoqiang , Benkirane-Jessel Nadia
Published: May 2022

Patient-derived tumoroid (PDT) has been developed and used for anti-drug screening in the last decade. As compared to other existing drug screening models, a PDT-based in vitro 3D cell culture model could preserve the histological and mutational characteristics of their corresponding tumors and mimic the tumor microenvironment. However, few studies have been carried out to improve the microvascular network connecting the PDT and its surrounding microenvironment, knowing that poor tumor-selective drug transport and delivery is one of the major reasons for both the failure of anti-cancer drug screens and resistance in clinical treatment. In this study, we formed vascularized PDTs in six days using multiple cell types which maintain the histopathological features of the original cancer tissue. Furthermore, our results demonstrated a vascular network connecting PDT and its surrounding microenvironment. This fast and promising PDT model opens new perspectives for personalized medicine: this model could easily be used to test all therapeutic treatments and could be connected with a microfluidic device for more accurate drug screening.
Urinary KIM-1 Correlates with the Subclinical Sequelae of Tubular Damage Persisting after the Apparent Functional Recovery from Intrinsic Acute Kidney Injury
Authors: Cuesta Cristina , Fuentes-Calvo Isabel , Sancho-Martinez Sandra M. , Valentijn Floris A. , Düwel Annette , Hidalgo-Thomas Omar A. , Agüeros-Blanco Consuelo , Benito-Hernández Adalberto , Ramos-Barron María A. , Gómez-Alamillo Carlos , Arias Manuel , Nguyen Tri Q. , Goldschmeding Roel , Martínez-Salgado Carlos , López-Hernández Francisco J.
Published: May 2022

Acute kidney injury (AKI) poses an increased risk factor for new AKI episodes, progression to chronic kidney disease, and death. A worsened evolution has been linked to an incomplete renal repair beyond the apparent functional recovery based on plasma creatinine (pCr) normalization. However, structural sequelae pass largely unnoticed due to the absence of specific diagnostic tools. The urinary kidney injury molecule 1 (KIM-1) participates in renal tissue damage and repair and is proposed as a biomarker of early and subclinical AKI. Thus, we study in this paper the evolution of KIM-1 urinary excretion alongside renal tissue sequelae after an intrinsic AKI episode induced by cisplatin in Wistar rats. Creatinine clearance, pCr, proteinuria and the fractional excretion of Na+ and glucose were used to monitor renal function. Renal tissue damage was blindly scored in kidney specimens stained with hematoxylin–eosin and periodic acid–Schiff. KIM-1 urinary excretion and renal mRNA expression were also assessed. Finally, we analyzed urinary KIM-1 in patients apparently recovered from AKI. Our results show that, after the normalization of the standard markers of glomerular filtration and tubular function, the extent of persistent histological findings of tissue repair correlates with the renal expression and urinary level of KIM-1 in rats. In addition, KIM-1 is also elevated in the urine of a significant fraction of patients apparently recovered from an AKI. Besides its potential utility in the early and subclinical diagnosis of renal damage, this study suggests a new application of urinary KIM-1 in the non-invasive follow-up of renal repair after AKI.
High Arterial Lactate Levels after Hepatic Resection Are Associated with Low Oxygen Delivery and Predict Severe Postoperative Complications
Authors: Gaspari Rita , Teofili Luciana , Ardito Francesco , Adducci Enrica , Vellone Maria , Mele Caterina , Orlando Nicoletta , Iacobucci Tiziana , Antonelli Massimo , Giuliante Felice
Published: May 2022

High End-Surgery Arterial Lactate Concentration (ES-ALC) predicts poor outcome after hepatectomy. The aim of this study was to identify intraoperative hemodynamic parameters predicting high ES-ALC during elective liver resection. Patients who underwent liver resection between 2017 and 2018, under FloTrac/EV1000TM hemodynamic monitoring, were included. The ES-ALC cutoff best predicting severe postoperative complications was identified. Association between high ES-ALC and preoperative and intraoperative variables was assessed. 108 patients were included; 90-day mortality was 0.9% and severe morbidity 14.8%. ES-ALC cutoff best discriminating severe complications was 5.05 mmol/L. Patients with ES-ALC > 5.0 mmol/L had a relative risk of severe complications of 2.8% (p = 0.004). High ES-ALC patients had longer surgery and ischemia duration, larger blood losses and higher requirements of fluids and blood transfusions. During surgery, hemoglobin concentration and oxygen delivery (DO2) decreased more significantly in patients with high ES-ALC, although they had similar values of stroke volume and cardiac output to those of other patients. At multivariate analysis, surgery duration and lowest recorded DO2 value were the strongest predictors of high ES-ALC. ES-ALC > 5.0 mmol/L in elective liver resection predicts postoperative morbidity and is essentially driven by the impaired DO2. Timely correction of blood losses might prevent the ES-ALC increase.
Inhaled Corticosteroids Selectively Alter the Microbiome and Host Transcriptome in the Small Airways of Patients with Chronic Obstructive Pulmonary Disease
Authors: Yip William , Li Xuan , Koelwyn Graeme J. , Milne Stephen , Leitao Filho Fernando Sergio , Yang Chen Xi , Hernández Cordero Ana I. , Yang Julia , Yang Cheng Wei Tony , Shaipanich Tawimas , van Eeden Stephan F. , Leung Janice M. , Lam Stephen , McNagny Kelly M. , Sin Don D.
Published: May 2022

Background: Patients with chronic obstructive pulmonary disease (COPD) are commonly treated with inhaled corticosteroid/long-acting ß2-agonist combination therapy. While previous studies have investigated the host–microbiome interactions in COPD, the effects of specific steroid formulations on this complex cross-talk remain obscure. Methods: We collected and evaluated data from the Study to Investigate the Differential Effects of Inhaled Symbicort and Advair on Lung Microbiota (DISARM), a randomized controlled trial. Bronchoscopy was performed on COPD patients before and after treatment with salmeterol/fluticasone, formoterol/budesonide or formoterol-only. Bronchial brush samples were processed for microbial 16S rRNA gene sequencing and host mRNA sequencing. Longitudinal changes in the microbiome at a community, phylum and genus level were correlated with changes in host gene expression using a Spearman’s rank correlation test. Findings: In COPD patients treated with salmeterol/fluticasone, the expression levels of 676 host genes were significantly correlated to changes in the alpha diversity of the small airways. At a genus level, the expression levels of 122 host genes were significantly related to changes in the relative abundance of Haemophilus. Gene enrichment analyses revealed the enrichment of pathways and biological processes related to innate and adaptive immunity and inflammation. None of these changes were evident in patients treated with formoterol/budesonide or formoterol alone. Interpretation: Changes in the microbiome following salmeterol/fluticasone treatment are related to alterations in the host transcriptome in the small airways of patients with COPD. These data may provide insights into why some COPD patients treated with inhaled corticosteroids may be at an increased risk for airway infection, including pneumonia. Funding: The Canadian Institute of Health Research, the British Columbia Lung Association, and an investigator-initiated grant from AstraZeneca.
Cross-Talk between Wnt Signaling and Src Tyrosine Kinase
Authors: Min Jung Ki , Park Hwee-Seon , Lee Yoon-Beom , Kim Jae-Gyu , Kim Jong-Il , Park Jae-Bong
Published: May 2022

Src, a non-receptor tyrosine kinase, was first discovered as a prototype oncogene and has been shown to critical for cancer progression for a variety of tissues. Src activity is regulated by a number of post-translational modifications in response to various stimuli. Phosphorylations of Src Tyr419 (human; 416 in chicken) and Src Tyr530 (human; 527 in chicken) have been known to be critical for activation and inactivation of Src, respectively. Wnt signaling regulates a variety of cellular functions including for development and cell proliferation, and has a role in certain diseases such as cancer. Wnt signaling is carried out through two pathways: β-catenin-dependent canonical and β-catenin-independent non-canonical pathways as Wnt ligands bind to their receptors, Frizzled, LRP5/6, and ROR1/2. In addition, many signaling components including Axin, APC, Damm, Dishevelled, JNK kinase and Rho GTPases contribute to these canonical and non-canonical Wnt pathways. However, the communication between Wnt signaling and Src tyrosine kinase has not been well reviewed as Src regulates Wnt signaling through LRP6 tyrosine phosphorylation. GSK-3β phosphorylated by Wnt also regulates Src activity. As Wnt signaling and Src mutually regulate each other, it is noted that aberrant regulation of these components give rise to various diseases including typically cancer, and as such, merit a closer look.
Editorial of the Special Issue “Targeted Therapies for Cancer”
Authors: Pastorino Fabio , Brignole Chiara
Published: May 2022

Cancer, the second leading cause of death worldwide, continues to represent an impressive challenge for researchers and clinicians [...]
The Effect of α-Mangostin and Cisplatin on Ovarian Cancer Cells and the Microenvironment
Authors: Borzdziłowska Paulina , Bednarek Ilona
Published: May 2022

Ovarian cancer is one of the cancers that, unfortunately, is detected at a late stage of development. The current use of treatment has many side effects. Notably, up to 20% of patients show cisplatin resistance. We assess the effects of cisplatin and/or α-mangostin, a natural plant derivative, on ovarian cancer cells and on the cancer cell microenvironment. The effect of cisplatin and/or α-mangostin on the following cells of ovarian cancer lines: A2780, TOV-21G, and SKOV-3 was verified using the XTT cytotoxicity assay. The separate and combined effects of tested drugs on ovarian cancer cell viability were assessed. We assessed the influence of chemotherapeutic agents on the possibility of modulating the microenvironment. For this purpose, we isolated exosomes from drug-treated and untreated ovarian cancer cells. We estimated the differences in the amounts of exosomes released from cancer cells (NTA technique). We also examined the effects of isolated exosome fractions on normal human cells (NHDF human fibroblast line). In the present study, we demonstrate that treatment of A2780, SKOV-3, and TOV-21G cells with α-mangostin in combination with cisplatin can allow a reduction in cisplatin concentration while maintaining the same cytotoxic effect. Ovarian cancer cells release a variable number of exosomes into the microenvironment when exposed to α-mangostin and/or cisplatin. However, it is important to note that the cargo carried by exosomes released from drug-treated cells may be significantly different.
Intrapericardial Administration of Secretomes from Menstrual Blood-Derived Mesenchymal Stromal Cells: Effects on Immune-Related Genes in a Porcine Model of Myocardial Infarction
Authors: de Pedro María Ángeles , Pulido María , Marinaro Federica , Álvarez Verónica , Báez-Díaz Claudia , Blanco Virginia , Silla-Castro Juan Carlos , Sanchez-Cabo Fátima , Sánchez-Margallo Francisco Miguel , Crisóstomo Verónica , Casado Javier G. , López Esther
Published: May 2022

Acute myocardial infarction (AMI) is a manifestation of ischemic heart disease where the immune system plays an important role in the re-establishment of homeostasis. We hypothesize that the anti-inflammatory activity of secretomes from menstrual blood-derived mesenchymal stromal cells (S-MenSCs) and IFNγ/TNFα-primed MenSCs (S-MenSCs*) may be considered a therapeutic option for the treatment of AMI. To assess this hypothesis, we have evaluated the effect of S-MenSCs and S-MenSCs* on cardiac function parameters and the involvement of immune-related genes using a porcine model of AMI. Twelve pigs were randomly divided into three biogroups: AMI/Placebo, AMI/S-MenSCs, and AMI/S-MenSCs*. AMI models were generated using a closed chest coronary occlusion-reperfusion procedure and, after 72 h, the different treatments were intrapericardially administered. Cardiac function parameters were monitored by magnetic resonance imaging before and 7 days post-therapy. Transcriptomic analyses in the infarcted tissue identified 571 transcripts associated with the Gene Ontology term Immune response, of which 57 were differentially expressed when different biogroups were compared. Moreover, a prediction of the interactions between differentially expressed genes (DEGs) and miRNAs from secretomes revealed that some DEGs in the infarction area, such as STAT3, IGFR1, or BCL6 could be targeted by previously identified miRNAs in secretomes from MenSCs. In conclusion, the intrapericardial administration of secretome early after infarction has a significant impact on the expression of immune-related genes in the infarcted myocardium. This confirms the immunomodulatory potential of intrapericardially delivered secretomes and opens new therapeutic perspectives in myocardial infarction treatment.
Towards Wearable Health Monitoring Devices
Authors: Pozdin Vladimir A. , Dieffenderfer James
Published: May 2022

Humans have searched far beyond our planet to understand the fundamental principles and mechanisms of life [...]
From Triboelectric Nanogenerator to Polymer-Based Biosensor: A Review
Authors: Lu Yin , Mi Yajun , Wu Tong , Cao Xia , Wang Ning
Published: May 2022

Nowadays, self-powered wearable biosensors that are based on triboelectric nanogenerators (TENGs) are playing an important role in the continuous efforts towards the miniaturization, energy saving, and intelligence of healthcare devices and Internets of Things (IoTs). In this review, we cover the remarkable developments in TENG−based biosensors developed from various polymer materials and their functionalities, with a focus on wearable and implantable self-powered sensors for health monitoring and therapeutic devices. The functions of TENGs as power sources for third-party biosensors are also discussed, and their applications in a number of related fields are concisely illustrated. Finally, we conclude the review with a discussion of the challenges and problems of leveraging TENG−based intelligent biosensors.
A Novel Perturbed Spiral Sheathless Chip for Particle Separation Based on Traveling Surface Acoustic Waves (TSAW)
Authors: Ji Miaomiao , Liu Yukai , Duan Junping , Zang Wenxuan , Wang Yongsheng , Qu Zeng , Zhang Binzhen
Published: May 2022

The combination of the new perturbed spiral channel and a slanted gold interfingered transducer (IDT) is designed to achieve precise dynamic separation of target particles (20 μm). The offset micropillar array solves the defect that the high-width flow (avoiding the occurrence of channel blockage) channel cannot realize the focusing of small particles (5 μm, 10 μm). The relationship between the maximum design gap of the micropillar (Smax) and the particle radius (a) is given: Smax = 4a, which not only ensures that small particles will not pass through the micropillar gap, but also is compatible with the appropriate flow rates. A non-offset micropillar array was used to remove 20 μm particles in the corner area. The innovation of a spiral channel structure greatly improves the separation efficiency and purity of the separation chip. The separation chip designed by us achieves deflection separation of 20 μm particles at 24.95–41.58 MHz (κ = 1.09–1.81), at a flow rate of 1.2 mL per hour. When f = 33.7 MHz (κ = 1.47), the transverse migration distance of 20 μm particles is the smallest, and the separation purity and efficiency are as high as 92% and 100%, respectively.
Correction: Peterson et al. Influence of Heart Rate Variability on Abstinence-Related Changes in Brain State in Everyday Drinkers. Brain Sci. 2021, 11, 817
Authors: Peterson Hope , Mayhugh Rhiannon E. , Bahrami Mohsen , Rejeski Walter Jack , Simpson Sean L. , Heilman Keri , Porges Stephen W. , Laurienti Paul J.
Published: May 2022

In the original article [...]
Flow Preserving Endovascular Treatment of Traumatic Pseudoaneurysms of the Distal Anterior Cerebral Artery—Case Reports and Review of Literature
Authors: Krůpa Petr , Krajina Antonín , Lojík Miroslav , Adamkov Jaroslav , Česák Tomas
Published: May 2022

Traumatic intracranial pseudoaneurysms (tIPAs) are a very rare pathology caused by blunt or penetrating head trauma. Diagnostic and therapeutic challenges of tIPAs are due to their unpredictable onset during the initial injury, or in a delayed manner, their unclear traumatic mechanism. Moreover, the presence of subarachnoid, subdural, or intraventricular hematoma may often cause them to be overlooked, which can potentially be followed by lethal rebleeding. Treatment of these lesions is controversial and on a case-by-case basis with regard to endovascular therapy or open surgery. We report two cases of three tIPAs of the distal anterior cerebral artery (dACA) with immediate and delayed onset after the trauma. Endovascular therapy resulted in complete obliteration of lesions with flow preservation in the parent artery using the flow diverter-assisted coiling strategy. The aim of this manuscript is to discuss the mechanism, angioanatomical characteristics, and current treatment options for these exceptional lesions.
Changing Times: The Impact of Digitalization on the Behavior of Professionals and Their Perception towards Development
Authors: Badea Ariadna , Paun Nicolae , Fleseriu Cristina , Paun Dragos
Published: May 2022

In 2020, the educational system was taken by surprise by the impact of the COVID-19 pandemic. Most of the educational institutions were delivering face-to-face classes and were forced to switch to online teaching in a very short period of time due to lockdown measures and the health and safety measures put in place by public authorities. In addition to universities, professional courses were also forced to be delivered online. Most of the time, these professional courses are important because they are directly linked to keeping the right to practice. The present paper focuses on the changing pattern in behavior of professionals and their acceptance of online courses. By applying over 1000 questionnaires in a timespan of more than one year, we have studied the impact of digitalization on the behavior and perception of professionals. We measured if the change towards online courses could be sustainable in the long run. The results of our study show that the behavior of professionals is different than those of students and that the online courses can be a long-term solution for education in professional environments.
Cardiovascular Effects of Cumulative Doses of Radioiodine in Differentiated Thyroid Cancer Patients with Type 2 Diabetes Mellitus
Authors: Stanciu Adina Elena , Stanciu Marcel Marian , Zamfirescu Anca , Gheorghe Dan Cristian
Published: May 2022

Radioiodine (131I) therapy for differentiated thyroid cancer (DTC) involves exposure of the whole body, including the heart, to ionizing radiation. This exposure to the subsequent risk of heart disease is uncertain, especially in patients with DTC associated with type 2 diabetes mellitus (DTC/+T2DM). The current study aimed to assess the relationship between left ventricular ejection fraction (LVEF), high cumulative 131I dose, and peripheral blood parameters in patients with DTC/−T2DM and DTC/+T2DM. The study enrolled 72 female patients with DTC/−T2DM and 24 with DTC/+T2DM who received cumulative 131I doses above 150 mCi (5.55 GBq). LVEF was lower in patients with concomitant T2DM than those without (p < 0.001). The cumulative 131I dosage was inversely correlated with LVEF only in DTC/−T2DM patients (r = −0.57, p < 0.001). In the DTC/+T2DM group, LVEF was negatively associated with absolute platelet count (r = −0.67, p < 0.001) and platelet-to-lymphocyte ratio (r = −0.76, p < 0.001). Our results demonstrate that exposure to high cumulative 131I doses has different cardiovascular effects in DTC/−T2DM and DTC/+T2DM.
Elevated Serotonin and NT-proBNP Levels Predict and Detect Carcinoid Heart Disease in a Large Validation Study
Authors: Levy Sonja , Kilgallen Aoife B. , Korse Catharina M. , Oerlemans Marish I. F. J. , Sluijter Joost P. G. , van Laake Linda W. , Valk Gerlof D. , Tesselaar Margot E. T.
Published: May 2022

Carcinoid heart disease (CHD) is a rare fibrotic cardiac complication of neuroendocrine tumors. Besides known biomarkers N-Terminal pro-B-type natriuretic peptide (NT-proBNP) and serotonin, activin A, connective tissue growth factor (CTGF), and soluble suppression of tumorigenicity 2 (sST2) have been suggested as potential biomarkers for CHD. Here, we validated the predictive/diagnostic value of these biomarkers in a case-control study of 114 patients between 1990 and 2021. Two time-points were analyzed: T0: liver metastasis without CHD for all patients. T1: confirmed CHD in cases (CHD+, n = 57); confirmed absence of CHD five or more years after liver metastasis in controls (CHD–, n = 57). Thirty-one (54%) and 25 (44%) females were included in CHD+ and CHD– patients, respectively. Median age was 57.9 years for CHD+ and 59.7 for CHD- patients (p = 0.290). At T0: activin A was similar across both groups (p = 0.724); NT-proBNP was higher in CHD+ patients (17 vs. 6 pmol/L, p = 0.016), area under the curve (AUC) 0.84, and the most optimal cut-off at 6.5 pmol/L. At T1: activin A was higher in CHD+ patients (0.65 vs. 0.38 ng/mL, p = 0.045), AUC 0.62, without an optimal cut-off value. NT-pro-BNP was higher in CHD+ patients (63 vs. 11 pmol/L, p < 0.001), AUC 0.89, with an optimal cut-off of 27 pmol/L. Serotonin (p = 0.345), sST2 (p = 0.867) and CTGF (p = 0.232) levels were similar across groups. This large validation study identified NT-proBNP as the superior biomarker for CHD. Patients with elevated serotonin levels and NT-proBNP levels between 6.5 and 27 pmol/L, and specifically >27 pmol/L, should be monitored closely for the development of CHD.