bluuebunny/crossref_metadata_2025 huggingface dataset:
Molecular Mechanisms Associated with ROS-Dependent Angiogenesis in Lower Extremity Artery Disease
Authors: Hutchings Greg , Kruszyna Łukasz , Nawrocki Mariusz J. , Strauss Ewa , Bryl Rut , Spaczyńska Julia , Perek Bartłomiej , Jemielity Marek , Mozdziak Paul , Kempisty Bartosz , Nowicki Michał , Krasiński Zbigniew
Published: May 2021

Currently, atherosclerosis, which affects the vascular bed of all vital organs and tissues, is considered as a leading cause of death. Most commonly, atherosclerosis involves coronary and peripheral arteries, which results in acute (e.g., myocardial infarction, lower extremities ischemia) or chronic (persistent ischemia leading to severe heart failure) consequences. All of them have a marked unfavorable impact on the quality of life and are associated with increased mortality and morbidity in human populations. Lower extremity artery disease (LEAD, also defined as peripheral artery disease, PAD) refers to atherosclerotic occlusive disease of the lower extremities, where partial or complete obstruction of peripheral arteries is observed. Decreased perfusion can result in ischemic pain, non-healing wounds, and ischemic ulcers, and significantly reduce the quality of life. However, the progressive atherosclerotic changes cause stimulation of tissue response processes, like vessel wall remodeling and neovascularization. These mechanisms of adapting the vascular network to pathological conditions seem to play a key role in reducing the impact of the changes limiting the flow of blood. Neovascularization as a response to ischemia induces sprouting and expansion of the endothelium to repair and grow the vessels of the circulatory system. Neovascularization consists of three different biological processes: vasculogenesis, angiogenesis, and arteriogenesis. Both molecular and environmental factors that may affect the process of development and growth of blood vessels were analyzed. Particular attention was paid to the changes taking place during LEAD. It is important to consider the molecular mechanisms underpinning vessel growth. These mechanisms will also be examined in the context of diseases commonly affecting blood vessel function, or those treatable in part by manipulation of angiogenesis. Furthermore, it may be possible to induce the process of blood vessel development and growth to treat peripheral vascular disease and wound healing. Reactive oxygen species (ROS) play an important role in regulation of essential cellular signaling pathways such as cell differentiation, proliferation, migration and apoptosis. With regard to the repair processes taking place during diseases such as LEAD, prospective therapeutic methods have been described that could significantly improve the treatment of vessel diseases in the future. Summarizing, regenerative medicine holds the potential to transform the therapeutic methods in heart and vessel diseases treatment.
The Role of NADPH Oxidase in Neuronal Death and Neurogenesis after Acute Neurological Disorders
Authors: Lee Song Hee , Lee Minwoo , Ko Dong Gyun , Choi Bo Young , Suh Sang Won
Published: May 2021

Oxidative stress is a well-known common pathological process involved in mediating acute neurological injuries, such as stroke, traumatic brain injury, epilepsy, and hypoglycemia-related neuronal injury. However, effective therapeutic measures aimed at scavenging free reactive oxygen species have shown little success in clinical trials. Recent studies have revealed that NADPH oxidase, a membrane-bound enzyme complex that catalyzes the production of a superoxide free radical, is one of the major sources of cellular reactive oxygen species in acute neurological disorders. Furthermore, several studies, including our previous ones, have shown that the inhibition of NADPH oxidase can reduce subsequent neuronal injury in neurological disease. Moreover, maintaining appropriate levels of NADPH oxidase has also been shown to be associated with proper neurogenesis after neuronal injury. This review aims to present a comprehensive overview of the role of NADPH oxidase in neuronal death and neurogenesis in multiple acute neurological disorders and to explore potential pharmacological strategies targeting the NADPH-related oxidative stress pathways.
The Ability to Normalise Energy Metabolism in Advanced COVID-19 Disease Seems to Be One of the Key Factors Determining the Disease Progression—A Metabolomic NMR Study on Blood Plasma
Authors: Baranovicova Eva , Bobcakova Anna , Vysehradsky Robert , Dankova Zuzana , Halasova Erika , Nosal Vladimir , Lehotsky Jan
Published: May 2021

Background: COVID-19 represents a severe inflammatory condition. Our work was designed to monitor the longitudinal dynamics of the metabolomic response of blood plasma and to reveal presumable discrimination in patients with positive and negative outcomes of COVID-19 respiratory symptoms. Methods: Blood plasma from patients, divided into subgroups with positive (survivors) and negative (worsening condition, non-survivors) outcomes, on Days 1, 3, and 7 after admission to hospital, was measured by NMR spectroscopy. Results: We observed changes in energy metabolism in both groups of COVID-19 patients; initial hyperglycaemia, indicating lowered glucose utilisation, was balanced with increased production of 3-hydroxybutyrate as an alternative energy source and accompanied by accelerated protein catabolism manifested by an increase in BCAA levels. These changes were normalised in patients with positive outcome by the seventh day, but still persisted one week after hospitalisation in patients with negative outcome. The initially decreased glutamine plasma level normalised faster in patients with positive outcome. Patients with negative outcome showed a more pronounced Phe/Tyr ratio, which is related to exacerbated and generalised inflammatory processes. Almost ideal discrimination from controls was proved. Conclusions: Distinct metabolomic responses to severe inflammation initiated by SARS-CoV-2 infection may serve towards complementary personalised pharmacological and nutritional support to improve patient outcomes.
Antimycotoxigenic Activity of Beetroot Extracts against Alternaria alternata Mycotoxins on Potato Crop
Authors: Youssef Nesrine H. , Qari Sameer H. , Behiry Said I. , Dessoky Eldessoky S. , El-Hallous Ehab I. , Elshaer Moustafa M. , Kordy Ahmed , Maresca Viviana , Abdelkhalek Ahmed , Heflish Ahmed A.
Published: May 2021

Alternaria species, mainly air-borne fungi, affect potato plants, causing black spots symptoms. Morphological identification, pathogenicity assessment, and internal transcribed spacer (ITS) molecular identification confirmed that all isolates were Alternaria alternata. The annotated sequences were deposited in GenBank under accession numbers MN592771–MN592777. HPLC analysis revealed that the fungal isolates KH3 (133,200 ng/g) and NO3 (212,000 ng/g) produced higher levels of tenuazonic acid (TeA) and alternariol monomethyl ether (AME), respectively. Beet ethanol extract (BEE) and beet methanol extract (BME) at different concentrations were used as antimycotoxins. BME decreased the production of mycotoxins by 66.99–99.79%. The highest TeA reduction rate (99.39%) was reported in the KH3 isolate with 150 µg/mL BME treatment. In comparison, the most effective AME reduction rate (99.79%) was shown in the NO3 isolate with 150 µg/mL BME treatment. In the same way, BEE application resulted in 95.60–99.91% mycotoxin reduction. The highest TeA reduction rate (99.91%) was reported in the KH3 isolate with 150 µg/mL BEE treatment, while the greatest AME reduction rate (99.68%) was shown in the Alam1 isolate with 75 µg/mL BEE treatment. GC-MS analysis showed that the main constituent in BME was the antioxidant compound 1-dodecanamine, n,n-dimethyl with a peak area of 43.75%. In contrast, oxirane, methyl- (23.22%); hexadecanoic acid, methyl ester (10.72%); and n-hexadecanoic acid (7.32%) were the main components in BEE found by GC-MS. They are probably antimicrobial molecules and have an effect on the mycotoxin in general. To our knowledge, this is the first study describing the antimycotoxigenic activity of beet extracts against A. alternata mycotoxins-contaminated potato crops in Egypt, aimed to manage and save the environment.
Influence of Soil Heterogeneity on the Contact Problems in Geotechnical Engineering
Authors: Gu Hao , Liu Kang
Published: May 2021

Contact problems are widely encountered in geotechnical engineering, such as the contact between soils and concrete used in earth and rockfill dams, tunnels and coastal levees. Due to the unknown contact region and contact forces, the contact problems have strong boundary nonlinearity. In addition, soils have been recognized as heterogeneous materials in geotechnical engineering. The existence of the soil heterogeneity increases the nonlinearity of the contact problems. Currently, the contact problems are mostly analysed without considering the soil heterogeneity, which may not reflect the contact behavior well. In order to investigate the influence of soil heterogeneity on the contact problems, in this paper, a simple plane-strain contact problem is analysed as an example. In this example, Young’s modulus is taken to be a spatially variable. The local average subdivision (LAS) is used to model the heterogeneity of Young’s modulus. The penalty method is utilised to determine the contact behavior. By the first use of linking the penalty method with the LAS, the proposed approach can be used to analyse the contact problems considering soil heterogeneity. The results show that the influence of soil heterogeneity on the elastic contact problems is significant. The contact forces of the heterogeneous case present apparent variation compared to the results of the homogeneous case. The distribution of the contact force at a specific point is also normal when Young’s modulus is normally distributed, moreover, the coefficient of variation (COV) and the horizontal scale of fluctuation of Young’s modulus affect the extent of variation of the normal contact forces. The standard deviation of the normal contact force increases with the increase of the COV and decreases with the increase of the horizontal scale of fluctuation of Young’s modulus. From the analyses, to better predict the deformation/stress in the contact problems, heterogeneity needs to be considered.
Recent Developments in Lignin- and Tannin-Based Non-Isocyanate Polyurethane Resins for Wood Adhesives—A Review
Authors: Aristri Manggar Arum , Lubis Muhammad Adly Rahandi , Yadav Sumit Manohar , Antov Petar , Papadopoulos Antonios N. , Pizzi Antonio , Fatriasari Widya , Ismayati Maya , Iswanto Apri Heri
Published: May 2021

This review article aims to summarize the potential of using renewable natural resources, such as lignin and tannin, in the preparation of NIPUs for wood adhesives. Polyurethanes (PUs) are extremely versatile polymeric materials, which have been widely used in numerous applications, e.g., packaging, footwear, construction, the automotive industry, the lighting industry, insulation panels, bedding, furniture, metallurgy, sealants, coatings, foams, and wood adhesives. The isocyanate-based PUs exhibit strong adhesion properties, excellent flexibility, and durability, but they lack renewability. Therefore, this study focused on the development of non-isocyanate polyurethane lignin and tannin resins for wood adhesives. PUs are commercially synthesized using polyols and polyisocyanates. Isocyanates are toxic, costly, and not renewable; thus, a search of suitable alternatives in the synthesis of polyurethane resins is needed. The reaction with diamine compounds could result in NIPUs based on lignin and tannin. The research on bio-based components for PU synthesis confirmed that they have good characteristics as an alternative for the petroleum-based adhesives. The advantages of improved strength, low curing temperatures, shorter pressing times, and isocyanate-free properties were demonstrated by lignin- and tannin-based NIPUs. The elimination of isocyanate, associated with environmental and human health hazards, NIPU synthesis, and its properties and applications, including wood adhesives, are reported comprehensively in this paper. The future perspectives of NIPUs’ production and application were also outlined.
Evaluation of Design Provisions for Horizontal Shear Strength in Composite Precast Concrete Beams with Different Interface Conditions
Authors: Oh Young-Hun , Moon Jeong-Ho
Published: May 2021

In a precast concrete (PC) composite beam, the horizontal interface between the PC beam and the cast-in-place (CIP) slab is located either on the compression side or on the tensile side of the cross-section. If the CIP slab is on the compression side, it becomes C-type interface, and if it is on the tensile side, it becomes T-type interface. Tensile cracks in the CIP slab may cause the horizontal shear strength of composite beams to decrease because of the reduced anchorage performance of shear reinforcements as well as the sliding on the interface. Such a tendency can be found from previous test results of specimens having T-type interface. In this study, the results of the push-off test and the beam flexure test were collected and analyzed to evaluate effects on the horizontal shear strength depending on the interface conditions, such as the interface location, surface roughness, concrete compressive strength, and clamping stress by shear connectors. The horizontal shear strength equations of ACI, PCI, AASHTO LRFD, and MC 2010 were evaluated with a database composed of 84 push-off tests and 95 beam tests from previous studies. According to the evaluation, evaluation results show that the design codes predict the horizontal shear strength conservatively for conditions other than the interface location. The horizontal shear strength deviated largely depending on the interface locations. The design codes conservatively estimate the horizontal shear strength for C-type interface, but the horizontal shear strength of T-type interface is overestimated. Based on current studies, it is recommended to use a friction coefficient of 0.7 as MC 2010 when calculating the horizontal shear strength of a composite beam with roughened T-type interface.
Mechanical Ventilator Parameter Estimation for Lung Health through Machine Learning
Authors: Oruganti Venkata Sanjay Sarma , Koenig Amie , Pidaparti Ramana M.
Published: May 2021

Patients whose lungs are compromised due to various respiratory health concerns require mechanical ventilation for support in breathing. Different mechanical ventilation settings are selected depending on the patient’s lung condition, and the selection of these parameters depends on the observed patient response and experience of the clinicians involved. To support this decision-making process for clinicians, good prediction models are always beneficial in improving the setting accuracy, reducing treatment error, and quickly weaning patients off the ventilation support. In this study, we developed a machine learning model for estimation of the mechanical ventilation parameters for lung health. The model is based on inverse mapping of artificial neural networks with the Graded Particle Swarm Optimizer. In this new variant, we introduced grouping and hierarchy in the swarm in addition to the general rules of particle swarm optimization to further improve its prediction performance of the mechanical ventilation parameters. The machine learning model was trained and tested using clinical data from canine and feline patients at the University of Georgia College of Veterinary Medicine. Our model successfully generated a range of parameter values for the mechanical ventilation applied on test data, with the average prediction values over multiple trials close to the target values. Overall, the developed machine learning model should be able to predict the mechanical ventilation settings for various respiratory conditions for patient’s survival once the relevant data are available.
Potential of Induced Pluripotent Stem Cells for Use in Gene Therapy: History, Molecular Bases, and Medical Perspectives
Authors: Fus-Kujawa Agnieszka , Mendrek Barbara , Trybus Anna , Bajdak-Rusinek Karolina , Stepien Karolina L. , Sieron Aleksander L.
Published: May 2021

Induced pluripotent stem cells (iPSCs) are defined as reprogrammed somatic cells exhibiting embryonic stem cell characteristics. Since their discovery in 2006, efforts have been made to utilize iPSCs in clinical settings. One of the promising fields of medicine, in which genetically patient-specific stem cells may prove themselves useful, is gene therapy. iPSCs technology holds potential in both creating models of genetic diseases and delivering therapeutic agents into the organism via auto-transplants, which reduces the risk of rejection compared to allotransplants. However, in order to safely administer genetically corrected stem cells into patients’ tissues, efforts must be made to establish stably pluripotent stem cells and reduce the risk of insertional tumorigenesis. In order to achieve this, optimal reprogramming factors and vectors must be considered. Therefore, in this review, the molecular bases of reprogramming safe iPSCs for clinical applications and recent attempts to translate iPSCs technology into the clinical setting are discussed.
Neuroinflammation in Alzheimer’s Disease
Authors: Onyango Isaac G. , Jauregui Gretsen V. , Čarná Mária , Bennett James P. , Stokin Gorazd B.
Published: May 2021

Alzheimer’s disease (AD) is a neurodegenerative disease associated with human aging. Ten percent of individuals over 65 years have AD and its prevalence continues to rise with increasing age. There are currently no effective disease modifying treatments for AD, resulting in increasingly large socioeconomic and personal costs. Increasing age is associated with an increase in low-grade chronic inflammation (inflammaging) that may contribute to the neurodegenerative process in AD. Although the exact mechanisms remain unclear, aberrant elevation of reactive oxygen and nitrogen species (RONS) levels from several endogenous and exogenous processes in the brain may not only affect cell signaling, but also trigger cellular senescence, inflammation, and pyroptosis. Moreover, a compromised immune privilege of the brain that allows the infiltration of peripheral immune cells and infectious agents may play a role. Additionally, meta-inflammation as well as gut microbiota dysbiosis may drive the neuroinflammatory process. Considering that inflammatory/immune pathways are dysregulated in parallel with cognitive dysfunction in AD, elucidating the relationship between the central nervous system and the immune system may facilitate the development of a safe and effective therapy for AD. We discuss some current ideas on processes in inflammaging that appear to drive the neurodegenerative process in AD and summarize details on a few immunomodulatory strategies being developed to selectively target the detrimental aspects of neuroinflammation without affecting defense mechanisms against pathogens and tissue damage.
Time-Frequency Characterization of Resting Brain in Bipolar Disorder during Euthymia—A Preliminary Study
Authors: Chrobak Adrian Andrzej , Bohaterewicz Bartosz , Sobczak Anna Maria , Marszał-Wiśniewska Magdalena , Tereszko Anna , Krupa Anna , Ceglarek Anna , Fafrowicz Magdalena , Bryll Amira , Marek Tadeusz , Dudek Dominika , Siwek Marcin
Published: May 2021

The goal of this paper is to investigate the baseline brain activity in euthymic bipolar disorder (BD) patients by comparing it to healthy controls (HC) with the use of a variety of resting state functional magnetic resonance imaging (rs-fMRI) analyses, such as amplitude of low frequency fluctuations (ALFF), fractional ALFF (f/ALFF), ALFF-based functional connectivity (FC), and r egional homogeneity (ReHo). We hypothesize that above-mentioned techniques will differentiate BD from HC indicating dissimilarities between the groups within different brain structures. Forty-two participants divided into two groups of euthymic BD patients (n = 21) and HC (n = 21) underwent rs-fMRI evaluation. Typical band ALFF, slow-4, slow-5, f/ALFF, as well as ReHo indexes were analyzed. Regions with altered ALFF were chosen as ROI for seed-to-voxel analysis of FC. As opposed to HC, BD patients revealed: increased ALFF in left insula; increased slow-5 in left middle temporal pole; increased f/ALFF in left superior frontal gyrus, left superior temporal gyrus, left middle occipital gyrus, right putamen, and bilateral thalamus. There were no significant differences between BD and HC groups in slow-4 band. Compared to HC, the BD group presented higher ReHo values in the left superior medial frontal gyrus and lower ReHo values in the right supplementary motor area. FC analysis revealed significant hyper-connectivity within the BD group between left insula and bilateral middle frontal gyrus, right superior parietal gyrus, right supramarginal gyrus, left inferior parietal gyrus, left cerebellum, and left supplementary motor area. To our best knowledge, this is the first rs-fMRI study combining ReHo, ALFF, f/ALFF, and subdivided frequency bands (slow-4 and slow-5) in euthymic BD patients. ALFF, f/ALFF, slow-5, as well as REHO analysis revealed significant differences between two studied groups. Although results obtained with the above methods enable to identify group-specific brain structures, no overlap between the brain regions was detected. This indicates that combination of foregoing rs-fMRI methods may complement each other, revealing the bigger picture of the complex resting state abnormalities in BD.
Intratumoral (Poly-ICLC) Therapy for Dogs with Advanced Cancers: First Report on Clinical Effectiveness, Quality of Life, and Adverse Events
Authors: Voges Alessandra Rinah Nogueira , Ubukata Rodrigo , Yazbek Karina Velloso Braga , Caballero Otávia Luisa , Salazar Andres Mario , Massoco Cristina de Oliveira , Dagli Maria Lucia Zaidan
Published: May 2021

Polyinosinic-polycytidylic acid-poly-l-lysine carboxymethylcellulose (poly-ICLC) is a synthetic double-stranded viral RNA analog widely tested as a component of human therapeutic cancer vaccines and as a standalone agent for treating human cancers. However, there are no reports on the use of poly-ICLC for treating canine cancers. This study aimed to investigate the clinical efficacy, quality of life (QL), and adverse events of poly-ICLC treatment in dogs with advanced cancers. The treatment protocol consisted of weekly intratumoral doses of poly-ICLC. The canine patients underwent clinical, laboratory, and imaging tests, and their owners answered weekly QL questionnaires. Fourteen canine patients with different types of spontaneous advanced tumors were enrolled. Most dogs had received prior conventional therapies. Five dogs received at least 12 doses of poly-ICLC: the injected tumor was stable in three dogs, there was a partial response in one, and the injected tumor significantly enlarged in the other. The QL scoring remained stable or increased in most cases. Mild adverse events related to poly-ICLC were observed in 10 of the 14 patients. The data showed that intratumoral poly-ICLC therapy was well tolerated in dogs with advanced cancers, with clinical benefit and improved QL scores observed in some dogs.
The PI3K/mTOR Pathway Is Targeted by Rare Germline Variants in Patients with Both Melanoma and Renal Cell Carcinoma
Authors: Hubert Jean-Noël , Suybeng Voreak , Vallée Maxime , Delhomme Tiffany M. , Maubec Eve , Boland Anne , Bacq Delphine , Deleuze Jean-François , Jouenne Fanélie , Brennan Paul , McKay James D. , Avril Marie-Françoise , Bressac-de Paillerets Brigitte , Chanudet Estelle
Published: May 2021

Background: Malignant melanoma and RCC have different embryonic origins, no common lifestyle risk factors but intriguingly share biological properties such as immune regulation and radioresistance. An excess risk of malignant melanoma is observed in RCC patients and vice versa. This bidirectional association is poorly understood, and hypothetic genetic co-susceptibility remains largely unexplored. Results: We hereby provide a clinical and genetic description of a series of 125 cases affected by both malignant melanoma and RCC. Clinical germline mutation testing identified a pathogenic variant in a melanoma and/or RCC predisposing gene in 17/125 cases (13.6%). This included mutually exclusive variants in MITF (p.E318K locus, N = 9 cases), BAP1 (N = 3), CDKN2A (N = 2), FLCN (N = 2), and PTEN (N = 1). A subset of 46 early-onset cases, without underlying germline variation, was whole-exome sequenced. In this series, thirteen genes were significantly enriched in mostly exclusive rare variants predicted to be deleterious, compared to 19,751 controls of similar ancestry. The observed variation mainly consisted of novel or low-frequency variants (<0.01%) within genes displaying strong evolutionary mutational constraints along the PI3K/mTOR pathway, including PIK3CD, NFRKB, EP300, MTOR, and related epigenetic modifier SETD2. The screening of independently processed germline exomes from The Cancer Genome Atlas confirmed an association with melanoma and RCC but not with cancers of established differing etiology such as lung cancers. Conclusions: Our study highlights that an exome-wide case-control enrichment approach may better characterize the rare variant-based missing heritability of multiple primary cancers. In our series, the co-occurrence of malignant melanoma and RCC was associated with germline variation in the PI3K/mTOR signaling cascade, with potential relevance for early diagnostic and clinical management.
More Than Meets the Eye: Scientific Rationale behind Molecular Imaging and Therapeutic Targeting of Prostate-Specific Membrane Antigen (PSMA) in Metastatic Prostate Cancer and Beyond
Authors: Hyväkkä Anniina , Virtanen Verneri , Kemppainen Jukka , Grönroos Tove J. , Minn Heikki , Sundvall Maria
Published: May 2021

Prostate cancer is the second most common cancer type in men globally. Although the prognosis for localized prostate cancer is good, no curative treatments are available for metastatic disease. Better diagnostic methods could help target therapies and improve the outcome. Prostate-specific membrane antigen (PSMA) is a transmembrane glycoprotein that is overexpressed on malignant prostate tumor cells and correlates with the aggressiveness of the disease. PSMA is a clinically validated target for positron emission tomography (PET) imaging-based diagnostics in prostate cancer, and during recent years several therapeutics have been developed based on PSMA expression and activity. The expression of PSMA in prostate cancer can be very heterogeneous and some metastases are negative for PSMA. Determinants that dictate clinical responses to PSMA-targeting therapeutics are not well known. Moreover, it is not clear how to manipulate PSMA expression for therapeutic purposes and develop rational treatment combinations. A deeper understanding of the biology behind the use of PSMA would help the development of theranostics with radiolabeled compounds and other PSMA-based therapeutic approaches. Along with PSMA several other targets have also been evaluated or are currently under investigation in preclinical or clinical settings in prostate cancer. Here we critically elaborate the biology and scientific rationale behind the use of PSMA and other targets in the detection and therapeutic targeting of metastatic prostate cancer.
A DNA Repair and Cell Cycle Gene Expression Signature in Pediatric High-Grade Gliomas: Prognostic and Therapeutic Value
Authors: Entz-Werlé Natacha , Poidevin Laetitia , Nazarov Petr V. , Poch Olivier , Lhermitte Benoit , Chenard Marie Pierre , Burckel Hélène , Guérin Eric , Fuchs Quentin , Castel David , Noel Georges , Choulier Laurence , Dontenwill Monique , Van Dyck Eric
Published: May 2021

Background: Pediatric high-grade gliomas (pHGGs) are the leading cause of mortality in pediatric neuro-oncology, displaying frequent resistance to standard therapies. Profiling DNA repair and cell cycle gene expression has recently been proposed as a strategy to classify adult glioblastomas. To improve our understanding of the DNA damage response pathways that operate in pHGGs and the vulnerabilities that these pathways might expose, we sought to identify and characterize a specific DNA repair and cell-cycle gene expression signature of pHGGs. Methods: Transcriptomic analyses were performed to identify a DNA repair and cell-cycle gene expression signature able to discriminate pHGGs (n = 6) from low-grade gliomas (n = 10). This signature was compared to related signatures already established. We used the pHGG signature to explore already transcriptomic datasets of DIPGs and sus-tentorial pHGGs. Finally, we examined the expression of key proteins of the pHGG signature in 21 pHGG diagnostic samples and nine paired relapses. Functional inhibition of one DNA repair factor was carried out in four patients who derived H3.3 K27M mutant cell lines. Results: We identified a 28-gene expression signature of DNA repair and cell cycle that clustered pHGGs cohorts, in particular sus-tentorial locations, in two groups. Differential protein expression levels of PARP1 and XRCC1 were associated to TP53 mutations and TOP2A amplification and linked significantly to the more radioresistant pHGGs displaying the worst outcome. Using patient-derived cell lines, we showed that the PARP-1/XRCC1 expression balance might be correlated with resistance to PARP1 inhibition. Conclusion: We provide evidence that PARP1 overexpression, associated to XRCC1 expression, TP53 mutations, and TOP2A amplification, is a new theranostic and potential therapeutic target.
Codon Bias Can Determine Sorting of a Potassium Channel Protein
Authors: Engel Anja J. , Kithil Marina , Langhans Markus , Rauh Oliver , Cartolano Matea , Van Etten James L. , Moroni Anna , Thiel Gerhard
Published: May 2021

Due to the redundancy of the genetic code most amino acids are encoded by multiple synonymous codons. It has been proposed that a biased frequency of synonymous codons can affect the function of proteins by modulating distinct steps in transcription, translation and folding. Here, we use two similar prototype K+ channels as model systems to examine whether codon choice has an impact on protein sorting. By monitoring transient expression of GFP-tagged channels in mammalian cells, we find that one of the two channels is sorted in a codon and cell cycle-dependent manner either to mitochondria or the secretory pathway. The data establish that a gene with either rare or frequent codons serves, together with a cell-state-dependent decoding mechanism, as a secondary code for sorting intracellular membrane proteins.
Enhancing the Functional and Environmental Properties of Asphalt Binders and Asphalt Mixtures Using Tourmaline Anion Powder Modification
Authors: Zhang Xiaorui , Zhou Xinxing , Xu Xinquan , Zhang Fan , Chen Leilei
Published: May 2021

Due to its good piezoelectric and thermoelectrical properties, tourmaline anion powder (TAP) can be used as a potential modifier to improve the piezoelectric, thermoelectric, rheological, and mechanical properties of asphalt binders and asphalt mixtures, respectively. This study was conducted to investigate the functional, piezoelectric, and thermoelectric properties of a TAP-modified asphalt binder (TAPMA) and the corresponding asphalt mixtures. In the study, the TAPMA’s environmental friendliness, such as the volatile organic compound (VOC) adsorption and metal immobilization, were investigated. Compared to TAP at 3.95 pC/N, the piezoelectric constant of TAPMA was found to be 3.42 pC/N. In general, the results indicated that TAP could potentially improve the functional properties of asphalt binders and asphalt mixtures, including the piezoelectric and thermoelectrical properties. With respect to environmental enhancement, the asphalt binder VOC emission reduced to 50% after TAP addition. In terms of metal immobilization, the heavy metals Fe and Ti exhibited the best stability followed by the alkali metals Li, K and Na, and lastly, Ca and Mg, respectively. Nonetheless, the emission concentrations of all the metals were below the regulatory threshold. Furthermore, the study findings also indicated that TAPMA can potentially adsorb the tail gas emissions of vehicles and heavy metals.
Development of New Composite Products Based on Flax Fibres
Authors: Tămaş-Gavrea Daniela-Roxana , Iştoan Raluca , Tiuc Ancuţa Elena , Dénes Tünde-Orsolya , Vasile Ovidiu , Constantinescu Horia
Published: May 2021

Plant fibres are materials that can increase energy savings, and they are being analysed for their reduced environmental impact. In this paper, three types of multi-layered panels were developed as environmentally friendly flax fibre-based products for building industry applications. The structural build-up of the panels is such that one layer of waste flax fibre was used as the core material in order to reduce the weight of the structure between two rigid perlite-based layers. The perlite was used in three varied grain sizes, resulting in three types of panels (S1, S2, S3). The mechanical, thermal and acoustic properties were recorded for all specimens. The influence of the perlite particles’ size, perforation diameter and perforation percentage of the multi-layered panels on the acoustic absorption properties was analysed and discussed. Summarising the results, the multi-layered composite panel S3 presented the best performance in regard to compressive strength and thermal conductivity, with S2 presenting the best bending strength. From the acoustic point of view, for the unperforated panels, the highest values of the sound absorption coefficient were obtained at 500 Hz for S1, α = 0.95, 315 Hz for S2, α = 0.89 and 400 Hz for S3, α = 0.84. The obtained values of the sound absorption coefficients were increased through the varied perforation diameters and percentages of the panels’ front face.
Adducts of Rhodium(II) Acetate and Rhodium(II) Pivalate with 1,8-Diazabicyclo[5.4.0]undec-7-ene
Authors: Fussell Eric D. , Darko Ampofo
Published: May 2021

In this article, we describe the synthesis of 1,8-diazabicyclo[5.4.0]undec-7-ene (DBU) adducts of rhodium(II) carboxylate complexes, [Rh2(μ-O2CCR3)4(DBU)2] (R = H (1), Me (2)). The DBU ligand is coordinated to the axial site in both adducts via the imido-nitrogen atom, and single-crystal X-ray diffraction analysis of 1 and 2 revealed structurally similar attributes between the compounds. The Rh–Rh bond distance is 2.4108(3) Å for 1 and 2.4143(2) Å for 2. The Rh–N distance is 2.2681(3) Å for compound 1 and 2.2587(10) Å for compound 2. Compound 1, however, crystallized with solvent molecules in its unit cell, and Hirshfeld surface analysis showed intermolecular C–H···O interactions between oxygen atoms of [Rh2(μ-O2CCH3)4] and the hydrogen of the chloroform solvent among other intermolecular close-contact interactions. The crystal structure of compound 2 was found to be devoid of solvent and showed weak intramolecular C–H···O interactions from the DBU axial ligand to the oxygens of the bridging acetates. Otherwise, Hirshfeld analysis showed that 2 was dominated by H···H interactions. UV-vis spectroscopy of both adducts was also conducted in different solvents to examine shifts attributed to the π*(Rh2) to σ*(Rh2) band.
Toward Commercialization of Stable Devices: An Overview on Encapsulation of Hybrid Organic-Inorganic Perovskite Solar Cells
Authors: Aranda Clara A. , Caliò Laura , Salado Manuel
Published: May 2021

Perovskite solar cells (PSCs) represent a promising technology for energy harvesting due to high power conversion efficiencies up to 26%, easy manufacturing, and convenient deposition techniques, leading to added advantages over other contemporary competitors. In order to promote this technology toward commercialization though, stability issues need to be addressed. Lately, many researchers have explored several techniques to improve the stability of the environmentally-sensitive perovskite solar devices. Challenges posed by environmental factors like moisture, oxygen, temperature, and UV-light exposure, could be overcome by device encapsulation. This review focuses the attention on the different materials, methods, and requirements for suitable encapsulated perovskite solar cells. A depth analysis on the current stability tests is also included, since accurate and reliable testing conditions are needed in order to reduce mismatching involved in reporting the efficiencies of PSC.
Stereotactic Radiotherapy in the Treatment of Paraneoplastic Vasculitis in Oligometastatic Renal Cell Carcinoma
Authors: Burgess Laura , Keenan Marissa , Zhou Alan Liang , Lypka Kiefer , Hasimja Saraqini Delvina , Yao Jeff , Martin Samuel , Morash Christopher , Watterson James , Canil Christina , MacRae Robert
Published: May 2021

Approximately 20% of renal cell carcinoma (RCC) is diagnosed because of paraneoplastic manifestations. RCC has been associated with a large variety of paraneoplastic syndromes (PNS), but it is rarely associated with PNS vasculitis. We present a case of a previously healthy male who presented with systemic vasculitis; bitemporal headaches, diplopia, polyarthritis, palpable purpura, tongue lesion, peri-orbital edema, scleritis, chondritis and constitutional symptoms. He was subsequently found to have oligometastatic RCC. Both his primary lesion and site of oligometastasis were treated with stereotactic radiotherapy (SBRT) and resulted in the resolution of his vasculitis, as well as sustained oncologic response. This is the first case to demonstrate that effective sustained treatment for PNS vasculitis due to oligometastatic RCC is possible with SBRT.
Lung Nodules in Melanoma Patients: Morphologic Criteria to Differentiate Non-Metastatic and Metastatic Lesions
Authors: Stadelmann Simone Alexandra , Blüthgen Christian , Milanese Gianluca , Nguyen-Kim Thi Dan Linh , Maul Julia-Tatjana , Dummer Reinhard , Frauenfelder Thomas , Eberhard Matthias
Published: May 2021

Lung nodules are frequent findings in chest computed tomography (CT) in patients with metastatic melanoma. In this study, we assessed the frequency and compared morphologic differences of metastases and benign nodules. We retrospectively evaluated 85 patients with melanoma (AJCC stage III or IV). Inclusion criteria were ≤20 lung nodules and follow-up using CT ≥183 days after baseline. Lung nodules were evaluated for size and morphology. Nodules with significant growth, nodule regression in line with RECIST assessment or histologic confirmation were judged to be metastases. A total of 438 lung nodules were evaluated, of which 68% were metastases. At least one metastasis was found in 78% of patients. A 10 mm diameter cut-off (used for RECIST) showed a specificity of 95% and a sensitivity of 20% for diagnosing metastases. Central location (n = 122) was more common in metastatic nodules (p = 0.009). Subsolid morphology (n = 53) was more frequent (p < 0.001), and calcifications (n = 13) were solely found in non-metastatic lung nodules (p < 0.001). Our data show that lung nodules are prevalent in about two-thirds of melanoma patients (AJCC stage III/IV) and the majority are metastases. Even though we found a few morphologic indicators for metastatic or non-metastatic lung nodules, morphology has limited value to predict the presence of lung metastases.
Burst of Corneal Dendritic Cells during Trastuzumab and Paclitaxel Treatment
Authors: Sterenczak Katharina A. , Stache Nadine , Bohn Sebastian , Allgeier Stephan , Köhler Bernd , Bartschat Andreas , George Christian , Guthoff Rudolf F. , Stachs Oliver , Stachs Angrit
Published: May 2021

During breast cancer therapy, paclitaxel and trastuzumab are both associated with adverse effects such as chemotherapy-induced peripheral neuropathy and other systemic side effects including ocular complications. Corneal nerves are considered part of the peripheral nervous system and can be imaged non-invasively by confocal laser scanning microscopy (CLSM) on the cellular level. Thus, in vivo CLSM imaging of structures of the corneal subbasal nerve plexus (SNP) such as sensory nerves or dendritic cells (DCs) can be a powerful tool for the assessment of corneal complications during cancer treatment. During the present study, the SNP of a breast cancer patient was analyzed over time by using large-scale in vivo CLSM in the course of paclitaxel and trastuzumab therapy. The same corneal regions could be re-identified over time. While the subbasal nerve morphology did not alter significantly, a change in dendritic cell density and an additional local burst within the first 11 weeks of therapy was detected, indicating treatment-mediated corneal inflammatory processes. Ocular structures such as nerves and dendritic cells could represent useful biomarkers for the assessment of ocular adverse effects during cancer therapy and their management, leading to a better visual prognosis.
Bacterial Autofluorescence Digital Imaging Guides Treatment in Stage 4 Pelvic Pressure Injuries: A Preliminary Case Series
Authors: Stiehl James B.
Published: May 2021

Pelvic pressure injuries in long-term care facilities are at high risk for undetected infection and complications from bacterial contamination and stalling of wound healing. Contemporary wound healing methods must address this problem with mechanical debridement, wound irrigation, and balanced dressings that reduce bacterial burden to enable the normal healing process. This study evaluated the impact of bacterial autofluorescence imaging to indicate wound bacterial contamination and guide treatment for severe stage 4 pelvic pressure injuries. A handheld digital imaging system was used to perform bacterial autofluorescence imaging in darkness on five elderly, high-risk, long-term care patients with advanced stage 4 pelvic pressure injuries who were being treated for significant bacterial contamination. The prescient findings of bacterial autofluorescence imaging instigated treatment strategies and enabled close monitoring of the treatment efficacy to ameliorate the bacterial contamination. Wound sepsis recurrence, adequate wound cleansing, and diagnosis of underlying periprosthetic total joint infection were confirmed with autofluorescence imaging showing regions of high bacterial load. By providing objective information at the point of care, imaging improved understanding of the bacterial infections and guided treatment strategies.
Diagnostic Challenges in Epithelioid Pleural Mesothelioma: Case Series with Support from Electron Microscopy
Authors: Fortarezza Francesco , Della Barbera Mila , Pezzuto Federica , Lunardi Francesca , Faccioli Eleonora , Pasello Giulia , Rea Federico , Rizzo Stefania , Calabrese Fiorella
Published: May 2021

The histological diagnosis of pleural epithelioid mesothelioma can be difficult in the case of rare variants or in the definition of neoplasm origin in patients with previous or concomitant tumours. Currently, several immunohistochemical reactions are available in the surgical pathologist’s armamentarium that allow us to obtain a more sensitive and specific diagnosis of malignant pleural mesothelioma. However, in some cases, the final interpretation remains inconclusive. Historically, ultrastructural examination has represented a useful tool for the definition of the mesothelial nature of neoplastic cells due to their peculiar morphological characteristics. The recent international guidelines for pathological diagnosis of pleural mesothelioma suggest the use of electron microscopy when the immunohistochemical reactions are equivocal or when further support of a diagnosis of mesothelioma is needed. This paper presents three cases of pleural epithelioid mesothelioma whose diagnoses were finally supported by ultrastructural examination.
Valuation of Wind Energy Turbines Using Volatility of Wind and Price
Authors: Greenberg Doron , Byalsky Michael , Yahalom Asher
Published: May 2021

The limitedness of the nonrenewable local energy resources in Israel, even in the background of the later gas fields’ findings, continues to force the state to devote various efforts towards ‘green’ energy development. These efforts include installations, both for the solar and for wind energy, thus improving the diversity of energy sources. While the standard discounted cash flow (DCF) method using the net present value (NPV) criterion is extensively adopted to evaluate investments, the standard DCF method is inappropriate for the rapidly changing investment climate and for the managerial flexibility in investment decisions. In recent years, the real options analysis (ROA) technique has been widely applied in many studies for the valuation of renewable energy investment projects. Taking into account the above background, we apply, in this study, the real options analysis approach for the valuation of wind energy turbines and apply it to the analysis of wind energy economic potential in Israel, which is the context of our work. We hypothesize that due to nature of wind energy production uncertainties, the ROA method is better than the alternative. The novelty of this paper includes the following: real world wind statistics of the Merom Golan site in Israel (velocity 3.73 m/s, with a standard deviation of 2.03 m/s), a realistic power generation estimation (power generation of 1205.84 kW with a standard deviation of about 0.5% in annual value which is worth about 1.3 M$ per annum), and an economic model to evaluate the profitability of such a project. We thus discuss the existing challenges of diversifying renewable energy sources in Israel by adding wind installations. Our motivation is to introduce a method which will allow investors and officials to take into account uncertainties when deciding in investing in such wind installations. The outcomes of the paper, which are obtained using the method of Weibull statistics and the Black–Scholes ROA technique, include the result that market price volatility adds to the uncertainties much more than any wind fluctuations, provided that the analysis is integrated over a long enough time.
Coupling between Source Rock and Reservoir of Shale Gas in Wufeng-Longmaxi Formation in Sichuan Basin, South China
Authors: Zhang Yuying , Jiang Shu , He Zhiliang , Li Yuchao , Xiao Dianshi , Chen Guohui , Zhao Jianhua
Published: May 2021

In order to analyze the main factors controlling shale gas accumulation and to predict the potential zone for shale gas exploration, the heterogeneous characteristics of the source rock and reservoir of the Wufeng-Longmaxi Formation in Sichuan Basin were discussed in detail, based on the data of petrology, sedimentology, reservoir physical properties and gas content. On this basis, the effect of coupling between source rock and reservoir on shale gas generation and reservation has been analyzed. The Wufeng-Longmaxi Formation black shale in the Sichuan Basin has been divided into 5 types of lithofacies, i.e., carbonaceous siliceous shale, carbonaceous argillaceous shale, composite shale, silty shale, and argillaceous shale, and 4 types of sedimentary microfacies, i.e., carbonaceous siliceous deep shelf, carbonaceous argillaceous deep shelf, silty argillaceous shallow shelf, and argillaceous shallow shelf. The total organic carbon (TOC) content ranged from 0.5% to 6.0% (mean 2.54%), which gradually decreased vertically from the bottom to the top and was controlled by the oxygen content of the bottom water. Most of the organic matter was sapropel in a high-over thermal maturity. The shale reservoir of Wufeng-Longmaxi Formation was characterized by low porosity and low permeability. Pore types were mainly <10 nm organic pores, especially in the lower member of the Longmaxi Formation. The size of organic pores increased sharply in the upper member of the Longmaxi Formation. The volumes of methane adsorption were between 1.431 m3/t and 3.719 m3/t, and the total gas contents were between 0.44 m3/t and 5.19 m3/t, both of which gradually decreased from the bottom upwards. Shale with a high TOC content in the carbonaceous siliceous/argillaceous deep shelf is considered to have significant potential for hydrocarbon generation and storage capacity for gas preservation, providing favorable conditions of the source rock and reservoir for shale gas.