bluuebunny/crossref_metadata_2025 huggingface dataset:
Impact of Tumor Side on Clinical Outcomes in Stage II and III Colon Cancer With Known Microsatellite Instability Status
Authors: Akce Mehmet , Zakka Katerina , Jiang Renjian , Williamson Shayla , Alese Olatunji B. , Shaib Walid L. , Wu Christina , Behera Madhusmita , El-Rayes Bassel F.
Published: March 2021

Background

Tumor sidedness as a prognostic factor in advanced stage colon cancer (CC) is well established. The impact of tumor sidedness on the clinical outcomes of stage II and III CC has not been well studied.

Methods

The National Cancer Database (NCDB) was utilized to identify patients with pathological stage II and III primary adenocarcinoma of the colon from 2010 to 2015 using ICD-O-3 morphology and topography codes: 8140-47, 8210-11, 8220-21, 8260-63, 8480-81, 8490 and C18.0, 18.2,18.3, 18.5,18.6, 18.7. Univariate (UVA) and multivariable (MVA) survival analyses and Kaplan–Meier Curves with Log-rank test were utilized to compare overall survival (OS) based on tumor location and treatment received.

Results

A total of 35,071 patients with stage II (n = 17,629) and III (n = 17,442) CC were identified. 51.3% female; 81.5% Caucasian; median age 66 (range, 18–90). Majority of stage II and III tumors were right sided, 61.2% (n = 10,794) and 56.0% (n = 9,763). Microsatellite instability high (MSI-H) was more common in stage II compared to III, 23.3% (n = 4,115) vs 18.2% (n = 3,171) (p < 0.0001). In stage II MSI-H CC right was more common than left, 78.3% (n = 3223) vs 21.7% (n = 892). There was no significant difference in survival between stage II MSI-H left vs right (5-year OS 76.2 vs 74.7%, p = 0.1578). Stage II MSS CC right was more common than left, 56.0% (n = 7571) vs 44.0% (n = 5943), and survival was better in the left vs right (5-year OS 73.2 vs 70.8%, p = 0.0029). Stage III MSI-H CC was more common in the right than in the left, 75.6% (n = 2,397) vs 24.4% (n = 774) and survival was better in the left (5-year OS 62.5 vs 56.5%, p = 0.0026). Stage III MSS CC was more common in the right than in the left, 51.6% (n = 7,366) vs 48.4% (n = 6,905), and survival was better in the left vs right (5-year OS 67.0 vs 54.4%, p < 0.001).

Conclusion

Survival was better in left sided tumors compared to right in stage II MSS, stage III MSS, and stage III MSI-H CC.
Transcriptome Analysis of Ivosidenib-Mediated Inhibitory Functions on Non-Small Cell Lung Cancer
Authors: Wu Juan , Chen Ru , Shen Huiqing , Yan Ting , Qian Yu , Zhang Yaping , Huang Zhuoya , Kong Pengzhou , Pang Min , Zhang Xinri
Published: March 2021

Ivosidenib is an isocitrate dehydrogenase mutant inhibitor that the US Food and Drug Administration recently approved for the treatment of leukemia. Studies suggested that ivosidenib may inhibit the progression of non-small cell lung cancer (NSCLC). In the present study, we explored RNAs and their potential regulatory mechanisms by which ivosidenib treats NSCLC cells. We used MTT assays, Transwell assays, and flow cytometry to measure the anti-tumor effects of ivosidenib in NSCLC cells. We performed whole transcriptome sequencing to determine differentially expressed mRNAs (DE-mRNAs) and non-coding RNAs (ncRNA). We used GO and KEGG pathway enrichment analyses to identify the functions and potential mechanisms. According to miRNA target interactions, we constructed a competing endogenous network. Ivosidenib inhibited the proliferation, invasion, and migration of NSCLC cells and inhibited tumor growth in vivo. We identified 212 DE-mRNAs, four DE-miRNAs, and 206 DE-lncRNAs in ivosidenib-treated NSCLC cells compared to untreated NSCLC cells. DE-mRNAs were significantly enriched in the cancer-associated pathways, including the TGF-β signaling pathway, the PI3K-Akt signaling pathway, the Jak-STAT signaling pathway, the MAPK signaling pathway, the Rap1 signaling pathway, and cell adhesion molecules. Based on the competing endogenous RNA hypothesis, we constructed lncRNA-miRNA-mRNA networks to elucidate the regulatory relationships between mRNA and ncRNA. We found that qRT-PCR results showed corresponding expression trends of differential genes with sequencing data. Our results provide insights into the molecular basis of ivosidenib suppression of NSCLC.
Case Report: Novel Likely Pathogenic ACTN2 Variant Causing Heterogeneous Phenotype in a Korean Family With Left Ventricular Non-compaction
Authors: Park Joonhong , Cho Yong Gon , Park Ha Wook , Cho Jung Sun
Published: March 2021

Left ventricular non-compaction (LVNC) is a very rare primary cardiomyopathy with a genetic etiology, resulting from the failure of myocardial development during embryogenesis, and it carries a high risk of left ventricular dysfunction, thromboembolic phenomenon, and malignant arrhythmias. Here, we report the first case of familial LVNC in Korea, caused by a novel ACTN2 missense variant. We performed duo exome sequencing (ES) to examine the genome of the proband and his father. A 15-year-old boy was admitted for the evaluation of exertional dyspnea for 2 weeks. He was diagnosed with LVNC with a dilated cardiomyopathy phenotype [left ventricular end-diastolic dimension 60 mm, interventricular septal dimension 8.2 mm by transthoracic echocardiography (TTE)]. For the screening of familial cardiomyopathy, TTE and cardiac magnetic resonance imaging (cMRI) were performed, which revealed hypertrophic and isolated LVNC in the proband's father and sister, respectively. In particular, the cMRI revealed dense hypertrabeculation with focal aneurysmal changes in the apical septal wall in the proband's father. ES of the father–son duo identified a novel heterozygous c.668T>C variant of the ACTN2 gene (NM_001103.3:c.668T>C, p.Leu223Pro; no rsID) as the candidate cause of autosomal dominant LVNC. Sanger sequencing confirmed this novel variant in the proband, his father, and sister, but not in the proband's grandmother. Even within families harboring the same variant, a variable risk of adverse outcomes is common. Therefore, familial screening for patients with LVNC associated with ACTN2 variant should be performed for early detection of the LVNC phenotype associated with poor outcomes, such as dilated LVNC.
Estimating the Magnetic Structure of an Erupting CME Flux Rope From AR12158 Using Data-Driven Modeling
Authors: Kilpua Emilia K. J. , Pomoell Jens , Price Daniel , Sarkar Ranadeep , Asvestari Eleanna
Published: March 2021

We investigate here the magnetic properties of a large-scale magnetic flux rope related to a coronal mass ejection (CME) that erupted from the Sun on September 12, 2014 and produced a well-defined flux rope in interplanetary space on September 14–15, 2014. We apply a fully data-driven and time-dependent magnetofrictional method (TMFM) using Solar Dynamics Observatory (SDO) magnetograms as the lower boundary condition. The simulation self-consistently produces a coherent flux rope and its ejection from the simulation domain. This paper describes the identification of the flux rope from the simulation data and defining its key parameters (e.g., twist and magnetic flux). We define the axial magnetic flux of the flux rope and the magnetic field time series from at the apex and at different distances from the apex of the flux rope. Our analysis shows that TMFM yields axial magnetic flux values that are in agreement with several observational proxies. The extracted magnetic field time series do not match well with in-situ components in direct comparison presumably due to interplanetary evolution and northward propagation of the CME. The study emphasizes also that magnetic field time-series are strongly dependent on how the flux rope is intercepted which presents a challenge for space weather forecasting.
Overexpression of CD44v8-10 in Colon Polyps—A Possible Key to Early Diagnosis
Authors: Dastych Milan , Hubatka Frantisek , Turanek-Knotigova Pavlina , Masek Josef , Kroupa Radek , Raška Milan , Turanek Jaroslav , Prochazka Lubomir
Published: March 2021

Background and aims: The majority of colorectal cancers arise from detectable adenomatous or serrated lesions. Here we demonstrate how deregulated alternative splicing of CD44 gene in diseased colon mucosa results in downregulation of standard isoform of CD44 gene (CD44s) and upregulation of variant isoform CD44v8-10. Our aim is to show that upregulation of CD44v8-10 isoform is a possible marker of precancerous lesion in human colon.

Methods: We analysed pairs of fresh biopsy specimen of large intestine in a cohort of 50 patients. We studied and compared alternative splicing profile of CD44 gene in colon polyps and adjoined healthy colon mucosa. We performed end-point and qRT PCR, western blotting, IHC staining and flow cytometry analyses.

Results: We detected more than five-fold overexpression of CD44v8-10 isoform and almost twenty-fold downregulation of standard isoform CD44s in colon polyps compared to adjoined healthy tissue with p = 0.018 and p < 0.001 in a cohort of 50 patients. Our results also show that aberrant splicing of CD44 occurs in both biologically distinct subtypes of colorectal adenoma possibly in ESRP-1 specific manner.

Conclusion: 92% of the colon polyp positive patients overexpressed CD44v8-10 isoform in their colon polyps while only 36% of them had positive fecal occult blood test which is currently a standard non-invasive screening technique.

Impact: We believe that our results are important for further steps leading to application of CD44v8-10 isoform as a biomarker of colorectal precancerosis in non-invasive detection. Early detection of colon precancerosis means successful prevention of colorectal carcinoma.
Exercise-Stimulated ROS Sensitive Signaling Pathways in Skeletal Muscle
Authors: Bouviere Jessica , Fortunato Rodrigo S. , Dupuy Corinne , Werneck-de-Castro Joao Pedro , Carvalho Denise P. , Louzada Ruy A.
Published: March 2021

Physical exercise represents a major challenge to whole-body homeostasis, provoking acute and adaptative responses at the cellular and systemic levels. Different sources of reactive oxygen species (ROS) have been described in skeletal muscle (e.g., NADPH oxidases, xanthine oxidase, and mitochondria) and are closely related to the physiological changes induced by physical exercise through the modulation of several signaling pathways. Many signaling pathways that are regulated by exercise-induced ROS generation, such as adenosine monophosphate-activated protein kinase (AMPK), mitogen activated protein kinase (MAPK), nuclear respiratory factor2 (NRF2), and PGC-1α are involved in skeletal muscle responses to physical exercise, such as increased glucose uptake, mitochondriogenesis, and hypertrophy, among others. Most of these adaptations are blunted by antioxidants, revealing the crucial role played by ROS during and after physical exercise. When ROS generation is either insufficient or exacerbated, ROS-mediated signaling is disrupted, as well as physical exercise adaptations. Thus, an understanding the limit between “ROS that can promote beneficial effects” and “ROS that can promote harmful effects” is a challenging question in exercise biology. The identification of new mediators that cause reductive stress and thereby disrupt exercise-stimulated ROS signaling is a trending on this topic and are covered in this current review.
MicroRNAs Regulating Hippo-YAP Signaling in Liver Cancer
Authors: Lee Na-Hyun , Kim So Jung , Hyun Jeongeun
Published: March 2021

Liver cancer is one of the most common cancers worldwide, and its prevalence and mortality rate are increasing due to the lack of biomarkers and effective treatments. The Hippo signaling pathway has long been known to control liver size, and genetic depletion of Hippo kinases leads to liver cancer in mice through activation of the downstream effectors yes-associated protein (YAP) and transcriptional coactivator with PDZ-binding motif (TAZ). Both YAP and TAZ not only reprogram tumor cells but also alter the tumor microenvironment to exert carcinogenic effects. Therefore, understanding the mechanisms of YAP/TAZ-mediated liver tumorigenesis will help overcome liver cancer. For decades, small noncoding RNAs, microRNAs (miRNAs), have been reported to play critical roles in the pathogenesis of many cancers, including liver cancer. However, the interactions between miRNAs and Hippo-YAP/TAZ signaling in the liver are still largely unknown. Here, we review miRNAs that influence the proliferation, migration and apoptosis of tumor cells by modulating Hippo-YAP/TAZ signaling during hepatic tumorigenesis. Previous findings suggest that these miRNAs are potential biomarkers and therapeutic targets for the diagnosis, prognosis, and treatment of liver cancer.
Immunological Aspects Related to Viral Infections in Severe Asthma and the Role of Omalizumab
Authors: Menzella Francesco , Ghidoni Giulia , Galeone Carla , Capobelli Silvia , Scelfo Chiara , Facciolongo Nicola Cosimo
Published: March 2021

Viral respiratory infections are recognized risk factors for the loss of control of allergic asthma and the induction of exacerbations, both in adults and children. Severe asthma is more susceptible to virus-induced asthma exacerbations, especially in the presence of high IgE levels. In the course of immune responses to viruses, an initial activation of innate immunity typically occurs and the production of type I and III interferons is essential in the control of viral spread. However, the Th2 inflammatory environment still appears to be protective against viral infections in general and in severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infections as well. As for now, literature data, although extremely limited and preliminary, show that severe asthma patients treated with biologics don’t have an increased risk of SARS-CoV-2 infection or progression to severe forms compared to the non-asthmatic population. Omalizumab, an anti-IgE monoclonal antibody, exerts a profound cellular effect, which can stabilize the effector cells, and is becoming much more efficient from the point of view of innate immunity in contrasting respiratory viral infections. In addition to the antiviral effect, clinical efficacy and safety of this biological allow a great improvement in the management of asthma.
ZnO Nanosheet-Coated TiZrPdSiNb Alloy as a Piezoelectric Hybrid Material for Self-Stimulating Orthopedic Implants
Authors: Careta Oriol , Fornell Jordina , Pellicer Eva , Ibañez Elena , Blanquer Andreu , Esteve Jaume , Sort Jordi , Murillo Gonzalo , Nogués Carme
Published: March 2021

A Ti-based alloy (Ti45Zr15Pd30Si5Nb5) with already proven excellent mechanical and biocompatibility features has been coated with piezoelectric zinc oxide (ZnO) to induce the electrical self-stimulation of cells. ZnO was grown onto the pristine alloy in two different morphologies: a flat dense film and an array of nanosheets. The effect of the combined material on osteoblasts (electrically stimulable cells) was analyzed in terms of proliferation, cell adhesion, expression of differentiation markers and induction of calcium transients. Although both ZnO structures were biocompatible and did not induce inflammatory response, only the array of ZnO nanosheets was able to induce calcium transients, which improved the proliferation of Saos-2 cells and enhanced the expression of some early differentiation expression genes. The usual motion of the cells imposes strain to the ZnO nanosheets, which, in turn, create local electric fields owing to their piezoelectric character. These electric fields cause the opening of calcium voltage gates and boost cell proliferation and early differentiation. Thus, the modification of the Ti45Zr15Pd30Si5Nb5 surface with an array of ZnO nanosheets endows the alloy with smart characteristics, making it capable of electric self-stimulation.
Nectin Cell Adhesion Molecule 4 (NECTIN4) Expression in Cutaneous Squamous Cell Carcinoma: A New Therapeutic Target?
Authors: Tanaka Yuka , Murata Maho , Oda Yoshinao , Furue Masutaka , Ito Takamichi
Published: March 2021

Cutaneous squamous cell carcinoma (cSCC) is the second most common skin cancer, and its incidence is rising because of the aging population. Nectin cell adhesion molecule 4 (NECTIN4) is involved in the progression of tumors and has attracted interest as a potential therapeutic target. However, little is known about the expression and significance of NECTIN4 in cSCC. The aim of this study was to determine the expression and function of NECTIN4 in cSCC. Immunohistological NECTIN4 expression was investigated in tissues from 34 cSCC patients. Using an A431 human SCC cell line, the role of NECTIN4 in the regulation of cell–cell attachment and migration and proliferation was assessed. NECTIN4 was expressed in most cSCC tissues and on the plasma membrane of A431 cells. Silencing of NECTIN4 prevented cell–cell attachment and induced the expression migration-related molecules, leading to an increase in cell migration. Knockdown of NECTIN4 downregulated extracellular signal-regulated kinase signaling, decreased cyclin D1 expression, and inhibited cell proliferation. These results show that NECTIN4 is expressed in cSCC and functions in the regulation of cell–cell interactions, as well as in the migration and proliferation of SCC cells. NECTIN4-targeted therapy may serve as a novel and promising treatment for cSCC.
Nanodiagnosis and Nanotreatment of Cardiovascular Diseases: An Overview
Authors: Sabir Fakhara , Barani Mahmood , Mukhtar Mahwash , Rahdar Abbas , Cucchiarini Magali , Zafar Muhammad Nadeem , Behl Tapan , Bungau Simona
Published: March 2021

Cardiovascular diseases (CVDs) are the world’s leading cause of mortality and represent a large contributor to the costs of medical care. Although tremendous progress has been made for the diagnosis of CVDs, there is an important need for more effective early diagnosis and the design of novel diagnostic methods. The diagnosis of CVDs generally relies on signs and symptoms depending on molecular imaging (MI) or on CVD-associated biomarkers. For early-stage CVDs, however, the reliability, specificity, and accuracy of the analysis is still problematic. Because of their unique chemical and physical properties, nanomaterial systems have been recognized as potential candidates to enhance the functional use of diagnostic instruments. Nanomaterials such as gold nanoparticles, carbon nanotubes, quantum dots, lipids, and polymeric nanoparticles represent novel sources to target CVDs. The special properties of nanomaterials including surface energy and topographies actively enhance the cellular response within CVDs. The availability of newly advanced techniques in nanomaterial science opens new avenues for the targeting of CVDs. The successful application of nanomaterials for CVDs needs a detailed understanding of both the disease and targeting moieties.
Contribution of Nanomaterials to the Development of Electrochemical Aptasensors for the Detection of Antimicrobial Residues in Food Products
Authors: Gaudin Valérie
Published: March 2021

The detection of antimicrobial residues in food products of animal origin is of utmost importance. Indeed antimicrobial residues could be present in animal derived food products because of animal treatments for curative purposes or from illegal use. The usual screening methods to detect antimicrobial residues in food are microbiological, immunological or physico-chemical methods. The development of biosensors to propose sensitive, cheap and quick alternatives to classical methods is constantly increasing. Aptasensors are one of the major trends proposed in the literature, in parallel with the development of immunosensors based on antibodies. The characteristics of electrochemical sensors (i.e., low cost, miniaturization, and portable instrumentation) make them very good candidates to develop screening methods for antimicrobial residues in food products. This review will focus on the recent advances in the development of electrochemical aptasensors for the detection of antimicrobial residues in food products. The contribution of nanomaterials to improve the performance characteristics of electrochemical aptasensors (e.g., Sensitivity, easiness, stability) in the last ten years, as well as signal amplification techniques will be highlighted.
A Sentinel-2 Dataset for Uganda
Authors: Ardö Jonas
Published: March 2021

Earth observation data provide useful information for the monitoring and management of vegetation- and land-related resources. The Framework for Operational Radiometric Correction for Environmental monitoring (FORCE) was used to download, process and composite Sentinel-2 data from 2018–2020 for Uganda. Over 16,500 Sentinel-2 data granules were downloaded and processed from top of the atmosphere reflectance to bottom of the atmosphere reflectance and higher-level products, totalling > 9 TB of input data. The output data include the number of clear sky observations per year, the best available pixel composite per year and vegetation indices (mean of EVI and NDVI) per quarter. The study intention was to provide analysis-ready data for all of Uganda from Sentinel-2 at 10 m spatial resolution, allowing users to bypass some basic processing and, hence, facilitate environmental monitoring.
A Diesel Engine with a Catalytic Piston Surface to Propel Small Aircraft at High Altitudes—A Theoretical Study
Authors: Karsenty Kadmiel , Tartakovsky Leonid , Sher Eran
Published: March 2021

Due to the oxygen shortage at high altitudes, the use of diesel engines in small aircraft is limited to a low ceiling level. Here, we propose to significantly extend the ceiling level by introducing an in-cylinder steam reforming system. In this arrangement, the fuel direct-injection assembly comprises of a two-stage process. In the first stage, a blend of methanol and water is injected into the hot previously compressed cylinder charge onto an in-cylinder catalyst. Residual heat is absorbed due to the blend evaporation and the steam-reforming process to produce hydrogen. In the second stage, diesel fuel with a lower ignition temperature than the hydrogen fuel is injected to initiate combustion, while the absorbed heat (from the first stage) is released through the hydrogen oxidation. Essentially, the absorbed heat is exploited to produce extra hydrogen fuel, which increases the cycle efficiency. In this arrangement, the in-cylinder oxygen content is significantly increased due to the additional oxygen atoms that are included in the methanol and in particular in the water molecules. These are released when the methanol and water are decomposed during the steam-reforming process. We show that owing to the addition of the oxygen content in the cylinder, the flight ceiling level can be extended from 5000 to 9000 ft, and that the indicated efficiency can be increase up to 6%.
Application of Lactic Acid Bacteria in Fermentation Processes to Obtain Tannases Using Agro-Industrial Wastes
Authors: García Méndez Martha Gabriela , Morales Martínez Thelma Karina , Ascacio Valdés Juan Alberto , Chávez González Mónica Lizeth , Flores Gallegos Adriana Carolina , Sepúlveda Leonardo
Published: March 2021

Bacteria have been used in the food industry to produce flavors, dyes, thickeners, and to increase food value, because bacterial fermentations favor the obtention of different metabolites such as tannins and different nutritional compounds in food. Lactiplantibacillus plantarum was one the first species to be studied for industrial purposes, and its efficacy to obtaining tannins using fermentation processes. Bacterial fermentation helps to obtain a product with an added value of better quality and without the need to use strong solvents that can reduce their quality and safety. To release tannins, it is necessary to subject the substrate to different conditions to activate the enzyme tannin acyl hydrolase (tannase). The tannase-released compounds can have beneficial effects on health such as antioxidant, anticancer and cardioprotective properties, among others. Therefore, this review analyzes tannase release and other metabolites by fermentation processes.
Future Transportation—An Open Access Journal
Authors: Wolfson Ouri E.
Published: March 2021

Transportation is an indispensable link for human progress, and essential to the development of civilizations [...]
Collaboration through Integrated BIM and GIS for the Design Process in Rail Projects: Formalising the Requirements
Authors: Kurwi Sahar , Demian Peter , Blay Karen B. , Hassan Tarek M.
Published: March 2021

Many of the obstacles to effective delivery of rail projects (in terms of cost, time and quality) can be traced back to poor collaboration across complex design teams and supply chains. As in any infrastructure delivery process, it is important to make decisions collaboratively at an early design stage. Advanced systems such as Building Information Modelling (BIM) and Geographic Information Systems (GIS) can facilitate collaboration during the decision-making process and boost work efficiencies. Such potential benefits are not realised because the roles of BIM and GIS in facilitating collaboration are not clearly understood or articulated. This paper aims to identify and articulate collaboration requirements during the design stage of rail projects. To achieve this, a mixed-method approach was employed to examine the issues that hinder collaboration in rail projects. An online questionnaire was designed to assess the state-of-art in BIM and GIS, followed by fifteen follow-up face to face interviews with experts to identify collaboration issues and suggestions to overcome them. The research identified the main challenges to effective collaboration and provided suggestions to overcome them. The main challenges were managing information and a reluctance to use new collaboration technologies. The main solution which emerged from the data was to develop an original Collaborative Plan of Work (CPW). The developed CPW is tailored to rail projects and has been formulated by combining the RIBA (Royal Institute of British Architects) Plan of Work and the GRIP Stages (Governance for Railway Investment Projects). This comprehensive plan of work, which is uniquely collaboration-focused, is significant because it can be further developed to formulate a precise process model for collaboration during the design process of rail projects. Such a process can (for example) be configured into the workflow prescribed by a Common Data Environment.
Agriculture Model Comparison Framework and MyGeoHub Hosting: Case of Soil Nitrogen
Authors: Bhar Anupam , Feddersen Benjamin , Malone Robert , Kumar Ratnesh
Published: March 2021

To be able to compare many agricultural models, a general framework for model comparison when field data may limit direct comparison of models is proposed, developed, and also demonstrated. The framework first calibrates the benchmark model against the field data, and next it calibrates the test model against the data generated by the calibrated benchmark model. The framework is validated for the modeling of the soil nutrient nitrogen (N), a critical component in the overall agriculture system modeling effort. The nitrogen dynamics and related carbon (C) dynamics, as captured in advanced agricultural modeling such as RZWQM, are highly complex, involving numerous states (pools) and parameters. Calibrating many parameters requires more time and data to avoid underfitting. The execution time of a complex model is higher as well. A study of tradeoff among modeling complexities vs. speed-up, and the corresponding impact on modeling accuracy, is desirable. This paper surveys soil nitrogen models and lists those by their complexity in terms of the number of parameters, and C-N pools. This paper also examines a lean soil N and C dynamics model and compares it with an advanced model, RZWQM. Since nitrate and ammonia are not directly measured in this study, we first calibrate RZWQM using the available data from an experimental field in Greeley, CO, and next use the daily nitrate and ammonia data generated from RZWQM as ground truth, against which the lean model’s N dynamics parameters are calibrated. In both cases, the crop growth was removed to zero out the plant uptake, to compare only the soil N-dynamics. The comparison results showed good accuracy with a coefficient of determination (R2) match of 0.99 and 0.62 for nitrate and ammonia, respectively, while affording significant speed-up in simulation time. The lean model is also hosted in MyGeoHub cyberinfrastructure for universal online access.
Challenges of ICC and FISH in the Field of Targeted Therapies from Cell Block to Smears
Authors: Echeveste Jose I. , Labiano Tania , Tejerina Eva , Argueta Allan , de Andrea Carlos , Lozano Maria D.
Published: March 2021

In the era of personalized medicine, there is an increasing demand for comprehensive and complex diagnosis using minimally invasive techniques. Nowadays, it is mandatory to integrate biomarkers in the diagnostic process, as well as in the treatment and clinical management of many cancer patients. Patients with non-small cell lung cancer (NSCLC), for instance, are frequently diagnosed in advanced stages, at a point when only cytological material or small biopsies can be obtained. This pathology constitutes an interesting challenge for the testing of biomarkers in cytology. Furthermore, there is a growing development of imaging techniques that guide non-invasive approaches to obtain small biopsies or cytological samples. This has allowed fine needle aspiration cytology and fine needle aspiration biopsy (FNAC, FNAB) to become front-line procedures in the management of patients with NSCLC. It is well known that the list of biomarkers to be tested in these patients continues to increase. Nevertheless, there are several of essential biomarkers that should always be analyzed in all patients with NSCLC, not only in non-squamous but also in some squamous carcinomas (SqCC). Some of them, such as PDL1, are tested by immunocytochemistry (ICC), while others, mainly ALK and ROS1, can be tested by ICC and confirmed using other techniques such a Fluorescence In Situ Hybridization (FISH). Other biomarkers, namely EGFR and BRAF mutations, are currently evaluated by polymerase chain reaction (PCR)-based techniques including Next-Generation Sequencing (NGS). In this review, we will address the particularities and challenges that ICC and FISH pose in different types of cytological samples from an eminently practical point of view.
Selected Papers from the Future Paths and Needs in Wave Modelling Workshop
Authors: Stansberg Carl Trygve , Rodrigues José Miguel
Published: March 2021

As an outcome of the International Workshop “Future needs and challenges in wave modelling”, held by SINTEF in Trondheim, Norway, 21–22 October 2019, this Special Issue includes 10 full Journal scientific papers [...]
Effect of Static Magnetic Field on Monascus ruber M7 Based on Transcriptome Analysis
Authors: Yang Shuyan , Zhou Hongyi , Dai Weihua , Xiong Juan , Chen Fusheng
Published: March 2021

The effects of a static magnetic field (SMF) on Monascus ruber M7 (M. ruber M7) cultured on potato dextrose agar (PDA) plates under SMF treatment at different intensities (5, 10, and 30 mT) were investigated in this paper. The results revealed that, compared with the control (CK, no SMF treatment), the SMF at all tested intensities did not significantly influence the morphological characteristics of M. ruber M7, while the intracellular and extracellular Monascus pigments (MPs) and extracellular citrinin (CIT) of M. ruber M7 were increased at 10 and 30 mT SMF but there was no impact on the MPs and CIT at 5 mT SMF. The transcriptome data of M. ruber M7 cultured at 30 mT SMF on PDA for 3 and 7 d showed that the SMF could increase the transcriptional levels of some relative genes with the primary metabolism, including the carbohydrate metabolism, amino acid metabolism, and lipid metabolism, especially in the early growing period (3 d). SMF could also affect the transcriptional levels of the related genes to the biosynthetic pathways of MPs, CIT, and ergosterol, and improve the transcription of the relative genes in the mitogen-activated protein kinase (MAPK) signaling pathway of M. ruber M7. These findings provide insights into a comprehensive understanding of the effects of SMF on filamentous fungi.
Recent Advances in Genome Editing Tools in Medical Mycology Research
Authors: Nargesi Sanaz , Kaboli Saeed , Thekkiniath Jose , Heidari Somayeh , Keramati Fatemeh , Seyedmousavi Seyedmojtaba , Hedayati Mohammad Taghi
Published: March 2021

Manipulating fungal genomes is an important tool to understand the function of target genes, pathobiology of fungal infections, virulence potential, and pathogenicity of medically important fungi, and to develop novel diagnostics and therapeutic targets. Here, we provide an overview of recent advances in genetic manipulation techniques used in the field of medical mycology. Fungi use several strategies to cope with stress and adapt themselves against environmental effectors. For instance, mutations in the 14 alpha-demethylase gene may result in azole resistance in Aspergillusfumigatus strains and shield them against fungicide’s effects. Over the past few decades, several genome editing methods have been introduced for genetic manipulations in pathogenic fungi. Application of restriction enzymes to target and cut a double-stranded DNA in a pre-defined sequence was the first technique used for cloning in Aspergillus and Candida. Genome editing technologies, including zinc-finger nucleases (ZFNs) and transcriptional activator-like effector nucleases (TALENs), have been also used to engineer a double-stranded DNA molecule. As a result, TALENs were considered more practical to identify single nucleotide polymorphisms. Recently, Class 2 type II Clustered Regularly Interspaced Short Palindromic Repeat (CRISPR)/Cas9 technology has emerged as a more useful tool for genome manipulation in fungal research.
Environmental Clonal Spread of Azole-Resistant Candida parapsilosis with Erg11-Y132F Mutation Causing a Large Candidemia Outbreak in a Brazilian Cancer Referral Center
Authors: Thomaz Danilo Y. , de Almeida João N. , Sejas Odeli N. E. , Del Negro Gilda M. B. , Carvalho Gabrielle O. M. H. , Gimenes Viviane M. F. , de Souza Maria Emilia B. , Arastehfar Amir , Camargo Carlos H. , Motta Adriana L. , Rossi Flávia , Perlin David S. , Freire Maristela P. , Abdala Edson , Benard Gil
Published: March 2021

Clonal outbreaks due to azole-resistant Candida parapsilosis (ARCP) isolates have been reported in numerous studies, but the environmental niche of such isolates has yet to be defined. Herein, we aimed to identify the environmental niche of ARCP isolates causing unremitting clonal outbreaks in an adult ICU from a Brazilian cancer referral center. C. parapsilosis sensu stricto isolates recovered from blood cultures, pericatheter skins, healthcare workers (HCW), and nosocomial surfaces were genotyped by multilocus microsatellite typing (MLMT). Antifungal susceptibility testing was performed by the EUCAST (European Committee for Antimicrobial Susceptibility Testing) broth microdilution reference method and ERG11 was sequenced to determine the azole resistance mechanism. Approximately 68% of isolates were fluconazole-resistant (76/112), including pericatheter skins (3/3, 100%), blood cultures (63/70, 90%), nosocomial surfaces (6/11, 54.5%), and HCW’s hands (4/28, 14.2%). MLMT revealed five clusters: the major cluster contained 88.2% of ARCP isolates (67/76) collected from blood (57/70), bed (2/2), pericatheter skin (2/3), from carts (3/7), and HCW’s hands (3/27). ARCP isolates were associated with a higher 30 day crude mortality rate (63.8%) than non-ARCP ones (20%, p = 0.008), and resisted two environmental decontamination attempts using quaternary ammonium. This study for the first time identified ARCP isolates harboring the Erg11-Y132F mutation from nosocomial surfaces and HCW’s hands, which were genetically identical to ARCP blood isolates. Therefore, it is likely that persisting clonal outbreak due to ARCP isolates was fueled by environmental sources. The resistance of Y132F ARCP isolates to disinfectants, and their potential association with a high mortality rate, warrant vigilant source control using effective environmental decontamination.
The Antibacterial and Remineralizing Effects of Biomaterials Combined with DMAHDM Nanocomposite: A Systematic Review
Authors: Clarin Alison , Ho Daphne , Soong Jana , Looi Cheryl , Ipe Deepak Samuel , Tadakamadla Santosh Kumar
Published: March 2021

Researchers have developed novel nanocomposites that incorporate additional biomaterials with dimethylaminohexadecyl methacrylate (DMAHDM) in order to reduce secondary caries. The aim of this review was to summarize the current literature and assess the synergistic antibacterial and remineralizing effects that may contribute to the prevention of secondary caries. An electronic search was undertaken in MEDLINE using PubMed, Embase, Scopus, Web of Science and Cochrane databases. The initial search identified 954 papers. After the removal of duplicates and screening the titles and abstracts, 15 articles were eligible for this review. The amalgamation of 2-methacryloyloxyethyl phosphorylcholine (MPC) and silver nanoparticles (AgNPs) with DMAHDM resulted in increased antibacterial potency. The addition of nanoparticles of amorphous calcium phosphate (NACP) and polyamidoamine dendrimers (PAMAM) resulted in improved remineralization potential. Further clinical studies need to be planned to explore the antibacterial and remineralizing properties of these novel composites for clinical success.
Nanoscale Piezoelectric Properties and Phase Separation in Pure and La-Doped BiFeO3 Films Prepared by Sol–Gel Method
Authors: Semchenko Alina V. , Sidsky Vitaly V. , Bdikin Igor , Gaishun Vladimir E. , Kopyl Svitlana , Kovalenko Dmitry L. , Pakhomov Oleg , Khakhomov Sergei A. , Kholkin Andrei L.
Published: March 2021

Pure BiFeO3 (BFO) and doped Bi0.9La0.1FeO3 (BLFO) thin films were prepared on Pt/TiO2/SiO2/Si substrates by a modified sol–gel technique using a separate hydrolysis procedure. The effects of final crystallization temperature and La doping on the phase structure, film morphology, and nanoscale piezoelectric properties were investigated. La doping and higher crystallization temperature lead to an increase in the grain size and preferred (102) texture of the films. Simultaneously, a decrease in the average effective piezoelectric coefficient (about 2 times in La-doped films) and an increase in the area of surface non-polar phase (up to 60%) are observed. Phase separation on the films’ surface is attributed to either a second phase or to a non-polar perovskite phase at the surface. As compared with undoped BFO, La-doping leads to an increase in the average grain size and self-polarization that is important for future piezoelectric applications. It is shown that piezoelectric activity is directly related to the films’ microstructructure, thus emphasizing the role of annealing conditions and La-doping that is frequently used to decrease the leakage current in BFO-based materials.
Chemical Functionalization of Carbon Nanotubes with Polymers: A Brief Overview
Authors: Díez-Pascual Ana Maria
Published: March 2021

Carbon nanotubes (CNTs), the one-dimensional allotropes of carbon, have attracted noteworthy research interest since their discovery in 1991 owing to their large aspect ratio, low mass density, and unique chemical, physical, and electronic properties that provide exciting possibilities for nanoscale applications. Nonetheless, two major issues should be considered when working with this sort of nanomaterial: their strong agglomerating tendency, since they are typically present as bundles or ropes of nanotubes, and the metallic impurities and carbonaceous fragments that go along with the CNTs. The successful utilization of CNTs in a wide variety of applications—in particular, in the field of polymer composites—depends on their uniform dispersion and the development of a strong chemical interaction with the polymeric matrix. To achieve these aims, chemical functionalization of their sidewalls and tips is required. In this article, a brief overview of the different approaches for CNT modification using polymers is provided, focusing on the covalent functionalization via “grafting to” or “grafting from” strategies. The characteristics and advantages of each approach are thoroughly discussed, including a few typical and recent examples. Moreover, applications of polymer-grafted CNTs as biosensors, membranes, energy storage substances, and EMI shielding are briefly described. Finally, future viewpoints in this vibrant research area are proposed.
Polyamine-Rich Diet Elevates Blood Spermine Levels and Inhibits Pro-Inflammatory Status: An Interventional Study
Authors: Soda Kuniyasu , Uemura Takeshi , Sanayama Hidenori , Igarashi Kazuei , Fukui Taro
Published: March 2021

The Japanese diet and the Mediterranean diet are rich in polyamines (spermidine and spermine). Increased polyamine intake elevated blood spermine levels, inhibited aging-associated pro-inflammatory status (increases in lymphocyte function-associated antigen-1 (LFA-1) on immune cells), suppressed aberrant gene methylation and extended the lifespan of mice. To test the effects of increased polyamine intake by humans, 30 healthy male volunteers were asked to eat polyamine-rich and ready-to-eat traditional Japanese food (natto) for 12 months. Natto with high polyamine content was used. Another 27 male volunteers were asked not to change their dietary pattern as a control group. The volunteers’ age of intervention and control groups ranged from 40 to 69 years (median 48.9 ± 7.9). Two subjects in the control group subsequently dropped out of the study. The estimated increases in spermidine and spermine intakes were 96.63 ± 47.70 and 22.00 ± 9.56 µmol per day in the intervention group, while no changes were observed in the control group. The mean blood spermine level in the intervention group gradually rose to 1.12 ± 0.29 times the pre-intervention level after 12 months, and were significantly higher (p = 0.019) than those in the control group. Blood spermidine did not increase in either group. LFA-1 on monocytes decreased gradually in the intervention group, and there was an inverse association between changes in spermine concentrations relative to spermidine and changes in LFA-1 levels. Contingency table analysis revealed that the odds ratio to decrease LFA-1 by increased polyamine intake was 3.927 (95% CI 1.116–13.715) (p = 0.032) when the effect of acute inflammation was excluded. The results in the study were similar to those of our animal experiments. Since methylation changes of the entire genome are associated with aging-associated pathologies and our previous studies showed that spermine-induced LFA-1 suppression was associated with the inhibition of aberrant gene methylation, the results suggest that dietary polyamine contributes to human health and longevity.
BipD of Burkholderia pseudomallei: Structure, Functions, and Detection Methods
Authors: Selvam Kasturi , Khalid Muhammad Fazli , Mustaffa Khairul Mohd Fadzli , Harun Azian , Aziah Ismail
Published: March 2021

Melioidosis is a severe disease caused by Burkholderia pseudomallei (B. pseudomallei), a Gram-negative environmental bacterium. It is endemic in Southeast Asia and Northern Australia, but it is underreported in many other countries. The principal routes of entry for B. pseudomallei are skin penetration, inhalation, and ingestion. It mainly affects immunocompromised populations, especially patients with type 2 diabetes mellitus. The laboratory diagnosis of melioidosis is challenging due to its non-specific clinical manifestations, which mimic other severe infections. The culture method is considered an imperfect gold standard for the diagnosis of melioidosis due to its low sensitivity. Antibody detection has low sensitivity and specificity due to the high seropositivity among healthy people in endemic regions. Antigen detection using various proteins has been tested for the rapid determination of B. pseudomallei; however, it presents certain limitations in terms of its sensitivity and specificity. Therefore, this review aims to frame the present knowledge of a potential target known as the Burkholderia invasion protein D (BipD), including future directions for its detection using an aptamer-based sensor (aptasensor).
Microbiologic Profiles of Patients with Dental Prosthetic Treatment and Periodontitis before and after Photoactivation Therapy—Randomized Clinical Trial
Authors: Mocanu Raluca Cristina , Martu Maria-Alexandra , Luchian Ionut , Sufaru Irina Georgeta , Maftei George Alexandru , Ioanid Nicoleta , Martu Silvia , Tatarciuc Monica
Published: March 2021

Fixed prosthodontic dental restorations can potentially affect the periodontal tissues and vice versa, the periodontium can influence the longevity and esthetic appearance of dental restorations. We proposed an investigation on total bacterial load, specific periodontal pathogens, and periodontal clinical parameters in patients with dental fixed prosthesis and different degrees of periodontal tissue loss that followed photoactivation therapy (PDT) adjunctive to scaling and root planing. The study was conducted on 160 subjects, which were randomly assigned to scaling and root planing (SRP) alone (52 subjects, 256 sites), SRP and chlorhexidine rinsing (58 subjects, 276 sites), and SRP plus PDT (50 subjects, 318 sites). Periodontal parameters (plaque index, bleeding on probing, probing depth, and clinical attachment loss), followed by total bacterial load and specific periodontal pathogens (Aggregatibacter actinomycetemcomitans, Porphyromonas gingivalis, Tannerella forsythia, and Treponema denticola) were examined in each patient at baseline, one and six months after. PDT exerted significant improvements both in clinical and microbiological load after one month, and these results were maintained 6 months after when compared to chlorhexidine rinsing or SRP alone, especially in severe periodontitis cases. Photoactivation therapy as an adjunctive periodontal therapeutic method was efficient in offering supplementary periodontal improvements in the clinical and microbiological parameters of patients with fixed dental prosthesis, particularly in severe periodontitis cases.
Photocatalytic Activity of S-Scheme Heterostructure for Hydrogen Production and Organic Pollutant Removal: A Mini-Review
Authors: Enesca Alexandru , Andronic Luminita
Published: March 2021

Finding new technologies and materials that provide real alternatives to the environmental and energy-related issues represents a key point on the future sustainability of the industrial activities and society development. The water contamination represents an important problem considering that the quantity and complexity of organic pollutant (such as dyes, pesticides, pharmaceutical active compounds, etc.) molecules can not be efficiently addressed by the traditional wastewater treatments. The use of fossil fuels presents two major disadvantages: (1) environmental pollution and (2) limited stock, which inevitably causes the energy shortage in various countries. A possible answer to the above issues is represented by the photocatalytic technology based on S-scheme heterostructures characterized by the use of light energy in order to degrade organic pollutants or to split the water molecule into its components. The present mini-review aims to outline the most recent achievements in the production and optimization of S-scheme heterostructures for photocatalytic applications. The paper focuses on the influence of heterostructure components and photocatalytic parameters (photocatalyst dosage, light spectra and intensity, irradiation time) on the pollutant removal efficiency and hydrogen evolution rate. Additionally, based on the systematic evaluation of the reported results, several perspectives regarding the future of S-scheme heterostructures were included.