bluuebunny/crossref_metadata_2025 huggingface dataset:
Echocardiographic Evaluation of the Mitral Valve in Cavalier King Charles Spaniels
Authors: Bagardi Mara , Bionda Arianna , Locatelli Chiara , Cortellari Matteo , Frattini Stefano , Negro Alessio , Crepaldi Paola , Brambilla Paola Giuseppina
Published: August 2020

This prospective cross-sectional study aimed to: (1) characterize echocardiographic features of mitral valve in MMVD affected Cavalier King Charles Spaniels (CKCS), focusing on dogs classified as American College of Veterinary Internal Medicine (ACVIM) class B1; (2) compare echocardiographic data in ACVIM B1 dogs divided on the basis of age at time of MMVD diagnosis, in order to understand if different aged subjects had different echocardiographic patterns. Length (AMVL), width (AMVW) and area (AMVA) of the anterior mitral valve leaflet, mitral valve prolapse, diameters of the mitral valve annulus in diastole (MVAd) and systole (MVAs) of 90 CKCS in different ACVIM classes, 64 of which in class B1, were measured. Valvular measurements were indexed to body weight using Wesselowski’s scaling exponents. The presence of heart murmur did not discriminate between A and B1 classes (p = 0.128). Heart enlargement was more frequent in males (r2 = 0.07, p = 0.013). Within class B1, older subjects showed significantly higher values of AMVA, AMVW, MVAd, MVAs and lower sphericity index (SI). Since many CKCS with MMVD have no murmur and their mitral valve has peculiarities, a specifically designed echocardiographic screening should be realized. In addition, different aged B1 dogs have different echocardiographic patterns that may imply different genetic and prognostic profiles.
Ex Vivo Murine Skin Model for B. burgdorferi Biofilm
Authors: Torres Jason P. , Senejani Alireza G. , Gaur Gauri , Oldakowski Michael , Murali Krithika , Sapi Eva
Published: August 2020

Borrelia burgdorferi, the causative agent of Lyme disease, has been recently shown to form biofilm structures in vitro and in vivo. Biofilms are tightly clustered microbes characterized as resistant aggregations that allow bacteria to withstand harsh environmental conditions, including the administration of antibiotics. Novel antibiotic combinations have recently been identified for B. burgdorferi in vitro, however, due to prohibiting costs, those agents have not been tested in an environment that can mimic the host tissue. Therefore, researchers cannot evaluate their true effectiveness against B. burgdorferi, especially its biofilm form. A skin ex vivo model system could be ideal for these types of experiments due to its cost effectiveness, reproducibility, and ability to investigate host–microbial interactions. Therefore, the main goal of this study was the establishment of a novel ex vivo murine skin biopsy model for B. burgdorferi biofilm research. Murine skin biopsies were inoculated with B. burgdorferi at various concentrations and cultured in different culture media. Two weeks post-infection, murine skin biopsies were analyzed utilizing immunohistochemical (IHC), reverse transcription PCR (RT-PCR), and various microscopy methods to determine B. burgdorferi presence and forms adopted as well as whether it remained live in the skin tissue explants. Our results showed that murine skin biopsies inoculated with 1 × 107 cells of B. burgdorferi and cultured in BSK-H + 6% rabbit serum media for two weeks yielded not just significant amounts of live B. burgdorferi spirochetes but biofilm forms as well. IHC combined with confocal and atomic force microscopy techniques identified specific biofilm markers and spatial distribution of B. burgdorferi aggregates in the infected skin tissues, confirming that they are indeed biofilms. In the future, this ex vivo skin model can be used to study development and antibiotic susceptibility of B. burgdorferi biofilms in efforts to treat Lyme disease effectively.
Medical-Grade Honey Kills Antibiotic-Resistant Bacteria and Prevents Amputation in Diabetics with Infected Ulcers: A Prospective Case Series
Authors: Nair Harikrishna K. R. , Tatavilis Nektarios , Pospíšilová Ivana , Kučerová Jana , Cremers Niels A. J.
Published: August 2020

Diabetic ulcers are at risk of becoming chronic and infected, as diabetics have hampered vascular structures, limiting oxygen and nutrient supply. These wounds can lead to pain, malodor, functional problems, and amputation. The current rise in antibiotic resistance demands for complementary therapies. Medical-grade honey (MGH) forms an attractive option because of its antimicrobial and pro-healing properties. We aim to show the beneficial effects of MGH in infected diabetic ulcers. We present six patients with infected diabetic ulcers, of which some were at risk of (further) amputation. Previous treatments with antibiotics, silver and alginate dressings, surgical closure, and maggot therapy were ineffective; therefore, the treatment was switched to the application of MGH. MGH therapy typically reduced the malodor in a couple of days and controlled infection within 2–3 weeks. MGH also enhanced wound healing by promoting granulation tissue formation, angiogenesis, and re-epithelialization, by decreasing inflammatory and oxidative stress and providing nutrients. Together, wound healing was enhanced, and the patient’s quality of life improved. MGH is safe and cost-effective for treating complicated diabetic wounds with (antibiotic-resistant) infections and at risk of amputation. MGH forms a promising alternative or complementary therapy to replace antibiotics for treating locally infected wounds.
Enhancing U-Net with Spatial-Channel Attention Gate for Abnormal Tissue Segmentation in Medical Imaging
Authors: Khanh Trinh Le Ba , Dao Duy-Phuong , Ho Ngoc-Huynh , Yang Hyung-Jeong , Baek Eu-Tteum , Lee Gueesang , Kim Soo-Hyung , Yoo Seok Bong
Published: August 2020

In recent years, deep learning has dominated medical image segmentation. Encoder-decoder architectures, such as U-Net, can be used in state-of-the-art models with powerful designs that are achieved by implementing skip connections that propagate local information from an encoder path to a decoder path to retrieve detailed spatial information lost by pooling operations. Despite their effectiveness for segmentation, these naïve skip connections still have some disadvantages. First, multi-scale skip connections tend to use unnecessary information and computational sources, where likable low-level encoder features are repeatedly used at multiple scales. Second, the contextual information of the low-level encoder feature is insufficient, leading to poor performance for pixel-wise recognition when concatenating with the corresponding high-level decoder feature. In this study, we propose a novel spatial-channel attention gate that addresses the limitations of plain skip connections. This can be easily integrated into an encoder-decoder network to effectively improve the performance of the image segmentation task. Comprehensive results reveal that our spatial-channel attention gate remarkably enhances the segmentation capability of the U-Net architecture with a minimal computational overhead added. The experimental results show that our proposed method outperforms the conventional deep networks in term of Dice score, which achieves 71.72%.
All-t2g Electronic Orbital Reconstruction of Monoclinic MoO2 Battery Material
Authors: Craco Luis , Leoni Stefano
Published: August 2020

Motivated by experiments, we undertake an investigation of electronic structure reconstruction and its link to electrodynamic responses of monoclinic MoO2. Using a combination of LDA band structure with DMFT for the subspace defined by the physically most relevant Mo 4d-bands, we unearth the importance of multi-orbital electron interactions to MoO2 parent compound. Supported by a microscopic description of quantum capacity we identify the implications of many-particle orbital reconstruction to understanding and evaluating voltage-capacity profiles intrinsic to MoO2 battery material. Therein, we underline the importance of the dielectric function and optical conductivity in the characterisation of existing and candidate battery materials.
Behaviour of Uniform Drava River Sand in Drained Condition—A Critical State Approach
Authors: Jagodnik Vedran , Kraus Ivan , Ivanda Sandi , Arbanas Željko
Published: August 2020

Numerous triaxial tests on sand and sand-like materials have been performed worldwide during the past several decades. Their results provided a development of the advanced soil constitutive models and laboratory testing devices, as well as the establishment of a worldwide database of different types of uniform sandy materials. From such research, the critical state and steady state theory has emerged as one of the most useful tool for the modelling of a soil behaviour. This paper presents the results of static drained tests performed on the uniform Drava River sand from the Osijek region in Croatia. The main aim was to determine the shear behaviour and critical state, given that these characteristics are mostly unknown for the tested sand material. A series of detail triaxial tests were performed in drained conditions for three different initial relative densities, DR, and two different loading directions; e.g., axial compression and axial extension. In total, 18 drained tests were performed. The study indicated that the value of 33.75∘ is the critical friction angle for the tested sand. The relative density of 57% is determined as the critical relative density. Additionally, the study confirmed the difference in critical state for compression and extension loading. In addition, the results indicate that the sample preparation procedure has an important impact on the critical state of loosely prepared sandy samples. These results give the first insights into the behaviour of the Drava River sand, which can generally contribute to the worldwide sand behaviour knowledge base.
The Potential of X-ray Photoelectron Spectroscopy for Determining Interface Dipoles of Self-Assembled Monolayers
Authors: Taucher Thomas C. , Zojer Egbert
Published: August 2020

In the current manuscript we assess to what extent X-ray photoelectron spectroscopy (XPS) is a suitable tool for probing the dipoles formed at interfaces between self-assembled monolayers and metal substrates. To that aim, we perform dispersion-corrected, slab-type band-structure calculations on a number of biphenyl-based systems bonded to an Au(111) surface via different docking groups. In addition to changing the docking chemistry (and the associated interface dipoles), the impacts of polar tail group substituents and varying dipole densities are also investigated. We find that for densely packed monolayers the shifts of the peak positions of the simulated XP spectra are a direct measure for the interface dipoles. In the absence of polar tail group substituents they also directly correlate with adsorption-induced work function changes. At reduced dipole densities this correlation deteriorates, as work function measurements probe the difference between the Fermi level of the substrate and the electrostatic energy far above the interface, while core level shifts are determined by the local electrostatic energy in the region of the atom from which the photoelectron is excited.
Towards the Use of Novel Materials in Shipbuilding: Assessing Thermal Performances of Fire-Doors by Self-Consistent Numerical Modelling
Authors: Kyaw Oo D’Amore Giada , Mauro Francesco , Marinò Alberto , Caniato Marco , Kašpar Jan
Published: August 2020

Nowadays, fire-doors optimization is approached by using consolidated design guidelines and traditional materials, such as rock wool. Then, selected solution is directly tested in a mandatory fire-test. Unfortunately, few pieces of information could be retrieved either if the test succeeds or fails, which makes both improvements in the design and use of innovative materials difficult. Thus, in this work, a self-consistent finite element method (FEM) analysis is developed and assessed against experimental fire-test results, highlighting the critical parameters affecting the numerical simulations. Using this tool, a new fiberglass-containing foam, with improved acoustic and mechanical properties, as compared to the rock-wool, is studied as a potential insulating material for on-board fire-doors. The assessment of the performance of the new material demonstrates that, contrary to common believe, the effective thermal insulation capacity is not necessarily the critical factor in determining the fire-resistance of a fire-door. Using the validated FEM analysis, it has been proven that the reduction of the thermal bridges originated at the door edges allows, firstly, for the attainment of a fire-door 37% thinner and 61% lighter with respect to a traditional one, and, secondly, the use of new material as insulator in fire-doors that, even if less thermally capable, could improve other properties of the door, as an example its soundproofing.
Mechanical Properties Assessment of Low-Content Capsule-Based Self-Healing Structural Composites
Authors: Tsilimigkra Xenia , Bekas Dimitrios , Kosarli Maria , Tsantzalis Stavros , Paipetis Alkiviadis , Kostopoulos Vassilis
Published: August 2020

Microcapsule-based carbon fiber reinforced composites were manufactured by wet layup, in order to assess their mechanical properties and determine their healing efficiency. Microcapsules at 10%wt. containing bisphenol-A epoxy, encapsulated in a urea formaldehyde (UF) shell, were employed with Scandium (III) Triflate (Sc (OTf)3) as the catalyst. The investigation was deployed with two main directions. The first monitored changes to the mechanical performance due to the presence of the healing agent within the composite. More precisely, a minor decrease in interlaminar fracture toughness (GIIC) (−14%), flexural strength (−12%) and modulus (−4%) compared to the reference material was reported. The second direction evaluated the healing efficiency. The experimental results showed significant recovery in fracture toughness up to 84% after the healing process, while flexural strength and modulus healing rates reached up to 14% and 23%, respectively. The Acoustic Emission technique was used to support the experimental results by the onsite monitoring.
Observation of an Electromagnetically Induced Grating in Cold 85Rb Atoms
Authors: Zhang Hengfei , Yuan Jinpeng , Dong Shichao , Wu Chaohua , Wang Lirong
Published: August 2020

Electromagnetically induced grating (EIG) is extensively investigated as an artificial periodic structure in recent years owed to its simple reconfiguration and flexible adjustability. We report the experimental observation of EIG in cold rubidium atoms. The coupling and probe lasers are corresponding to the 5S1/2−5P1/2 and 5S1/2−5P3/2 transitions of a V-type electromagnetically induced transparency (EIT) configuration, respectively. A clear spatial intensity distribution of the probe laser with distinguished third-order diffraction pattern is recorded to character the EIG. The influence of the pertinent experimental parameters, such as coupling laser intensity and two-photon detuning on the diffraction pattern is investigated in detail. This is the first observation in visual form of the EIG in cold rubidium atoms. These results may potentially provide a nondestructive method to image cold atoms and pave the way for investigating non-Hermitian physics and the control of light dynamics.
Towards Nearly Zero Energy and Environmentally Sustainable Agritourisms: The Effectiveness of the Application of the European Ecolabel Brand
Authors: Cirrincione Laura , La Gennusa Maria , Peri Giorgia , Rizzo Gianfranco , Scaccianoce Gianluca
Published: August 2020

Tourism represents an important economic driver in Italy, being responsible for approximately 13.2% of the total GDP (a value higher than the reference European average) and for nearly 10% of the regional GDP. Among the touristic sectors, the agritourist ones show a persistent growth, experiencing in 2019 a 6.7 point percentage improvement compared to the 2017 figures. Given this situation, the transition towards a low-carbon path, affecting the building sector for some time, should also involve agritourist buildings, through the release of EU directives, member state laws, and technical rules. On the other hand, agritourism sites could be awarded the Community EU Ecolabel. Unfortunately, awarding the EU environmental excellence brand implies the availability of several data on building energy behavior that should then be managed by complex evaluation tools. To overcome this issue, the use of the simplified ARERA (Italian Regulatory Authority for Energy Networks and Environment) technical datasheets, issued to assess environmental improvements consequent to energy efficiency interventions in the urban residential building stock, is proposed. The application of this tool totally avoids using building computer-based simulation models, thus facilitating the preparation of the EU Ecolabel request documentation by agritourism owners. Being awarded the Community EU Ecolabel also implies approaching a net zero energy condition because of a lower energy consumption and a minor recourse to fossil fuels. For this purpose, an application of an easy graphical method, previously developed for residential and commercial buildings, which visually represents improvements achievable by a given agritourism when implementing energy efficiency measures, is presented.
Planar D-π-A Configured Dimethoxy Vinylbenzene Based Small Organic Molecule for Solution-Processed Bulk Heterojunction Organic Solar Cells
Authors: Alam Shabaz , Akhtar M. Shaheer , Abdullah  , Kim Eun-Bi , Shin Hyung-Shik , Ameen Sadia
Published: August 2020

A new and effective planar D-π-A configured small organic molecule (SOM) of 2-5-(3,5-dimethoxystyryl)thiophen-2-yl)methylene)-1H-indene-1,3(2H)-dione, abbreviated as DVB-T-ID, was synthesized using 1,3-indanedione acceptor and dimethoxy vinylbenzene donor units, connected through a thiophene π-spacer. The presence of a dimethoxy vinylbenzene unit and π-spacer in DVB-T-ID significantly improved the absorption behavior by displaying maximum absorbance at ~515 nm, and the reasonable band gap was estimated as ~2.06 eV. The electronic properties revealed that DVB-T-ID SOMs exhibited promising HOMO (−5.32 eV) and LUMO (−3.26 eV). The synthesized DVB-T-ID SOM was utilized as donor material for fabricating solution-processed bulk heterojunction organic solar cells (BHJ-OSCs) and showed a reasonable power conversion efficiency (PCE) of ~3.1% with DVB-T-ID:PC61BM (1:2, w/w) active layer. The outcome of this work clearly reflects that synthesized DVB-T-ID based on 1,3-indanedione units is a promising absorber (donor) material for BHJ-OSCs.
Long-Term Variability in Potential Evapotranspiration, Water Availability and Drought under Climate Change Scenarios in the Awash River Basin, Ethiopia
Authors: Tadese Mahtsente , Kumar Lalit , Koech Richard
Published: August 2020

Understanding the hydrological processes of a watershed in response to climate change is vital to the establishment of sustainable environmental management strategies. This study aimed to evaluate the variability of potential evapotranspiration (PET) and water availability in the Awash River Basin (ARB) under different climate change scenarios and to relate these with long-term drought occurrences in the area. The PET and water availability of the ARB was estimated during the period of 1995–2009 and two future scenarios (2050s and 2070s). The representative concentration pathways (RCP4.5 and RCP8.5) simulations showed an increase in the monthly mean PET from March to August in the 2050s, and all the months in the 2070s. The study also identified a shortage of net water availability in the majority of the months investigated and the occurrence of mild to extreme drought in about 40–50% of the analysed years at the three study locations (Holetta, Koka Dam, and Metehara). The decrease in water availability and an increase in PET, combined with population growth, will aggravate the drought occurrence and food insecurity in the ARB. Therefore, integrated watershed management systems and rehabilitation of forests, as well as water bodies, should be addressed in the ARB to mitigate climate change and water shortage in the area.
Combining MWL and MSG SEVIRI Satellite Signals for Rainfall Detection and Estimation
Authors: Kumah Kingsley K. , Hoedjes Joost C. B. , David Noam , Maathuis Ben H. P. , Gao H. Oliver , Su Bob Z.
Published: August 2020

Accurate rainfall detection and estimation are essential for many research and operational applications. Traditional rainfall detection and estimation techniques have achieved considerable success but with limitations. Thus, in this study, the relationships between the gauge (point measurement) and the microwave links (MWL) rainfall (line measurement), and the MWL to the satellite observations (area-wide measurement) are investigated for (area-wide) rainfall detection and rain rate retrieval. More precisely, we investigate if the combination of MWL with Meteosat Second Generation (MSG) satellite signals could improve rainfall detection and rainfall rate estimates. The investigated procedure includes an initial evaluation of the MWL rainfall estimates using gauge measurements, followed by a joint analysis of the rainfall estimates with the satellite signals by means of a conceptual model in which clouds with high cloud top optical thickness and large particle sizes have high rainfall probabilities and intensities. The analysis produced empirical thresholds that were used to test the capability of the MSG satellite data to detect rainfall on the MWL. The results from Kenya, during the “long rains” of 2013, 2014, and 2018 show convincing performance and reveal the potential of MWL and MSG data for area-wide rainfall detection.
Kripke-Style Models for Logics of Evidence and Truth
Authors: Antunes Henrique , Carnielli Walter , Kapsner Andreas , Rodrigues Abilio
Published: August 2020

In this paper, we propose Kripke-style models for the logics of evidence and truth LETJ and LETF. These logics extend, respectively, Nelson’s logic N4 and the logic of first-degree entailment (FDE) with a classicality operator ∘ that recovers classical logic for formulas in its scope. According to the intended interpretation here proposed, these models represent a database that receives information as time passes, and such information can be positive, negative, non-reliable, or reliable, while a formula ∘A means that the information about A, either positive or negative, is reliable. This proposal is in line with the interpretation of N4 and FDE as information-based logics, but adds to the four scenarios expressed by them two new scenarios: reliable (or conclusive) information (i) for the truth and (ii) for the falsity of a given proposition.
Stress Changes the Resting-State Cortical Flow of Information from Distributed to Frontally Directed Patterns
Authors: Keshmiri Soheil
Published: August 2020

Despite converging evidence on the involvement of large-scale distributed brain networks in response to stress, the effect of stress on the components of these networks is less clear. Although some studies identify higher regional activities in response to stress, others observe an opposite effect in the similar regions. Studies based on synchronized activities and coactivation of these components also yield similar differing results. However, these differences are not necessarily contradictory once we observe the effect of stress on these functional networks in terms of the change in information processing capacity of their components. In the present study, we investigate the utility of such a shift in the analysis of the effect of stress on distributed cortical regions through quantification of the flow of information among them. For this purpose, we use the self-assessed responses of 216 individuals to stress-related questionnaires and systematically select 20 of them whose responses showed significantly higher and lower susceptibility to stress. We then use these 20 individuals’ resting-state multi-channel electroencephalography (EEG) recordings (both Eyes-Closed (EC) and Eyes-Open (EO) settings) and compute the distributed flow of information among their cortical regions using transfer entropy (TE). The contribution of the present study is three-fold. First, it identifies that the stress-susceptibility is characterized by the change in flow of information in fronto-parietal brain network. Second, it shows that these regions are distributed bi-hemispherically and are sufficient to significantly differentiate between the individuals with high versus low stress-susceptibility. Third, it verifies that the high stress-susceptibility is markedly associated with a higher parietal-to-frontal flow of information. These results provide further evidence for the viewpoint in which the brain’s modulation of information is not necessarily accompanied by the change in its regional activity. They further construe the effect of stress in terms of a disturbance that disrupts the flow of information among the brain’s distributed cortical regions. These observations, in turn, suggest that some of the differences in the previous findings perhaps reflect different aspects of impaired distributed brain information processing in response to stress. From a broader perspective, these results posit the use of TE as a potential diagnostic/prognostic tool in identification of the effect of stress on distributed brain networks that are involved in stress-response.
Lipid Modulation in the Formation of β-Sheet Structures. Implications for De Novo Design of Human Islet Amyloid Polypeptide and the Impact on β-Cell Homeostasis
Authors: Martínez-Navarro Israel , Díaz-Molina Raúl , Pulido-Capiz Angel , Mas-Oliva Jaime , Luna-Reyes Ismael , Rodríguez-Velázquez Eustolia , Rivero Ignacio A. , Ramos-Ibarra Marco A. , Alatorre-Meda Manuel , García-González Victor
Published: August 2020

Human islet amyloid polypeptide (hIAPP) corresponds to a 37-residue hormone present in insulin granules that maintains a high propensity to form β-sheet structures during co-secretion with insulin. Previously, employing a biomimetic approach, we proposed a panel of optimized IAPP sequences with only one residue substitution that shows the capability to reduce amyloidogenesis. Taking into account that specific membrane lipids have been considered as a key factor in the induction of cytotoxicity, in this study, following the same design strategy, we characterize the effect of a series of lipids upon several polypeptide domains that show the highest aggregation propensity. The characterization of the C-native segment of hIAPP (residues F23-Y37), together with novel variants F23R and I26A allowed us to demonstrate an effect upon the formation of β-sheet structures. Our results suggest that zwitterionic phospholipids promote adsorption of the C-native segments at the lipid-interface and β-sheet formation with the exception of the F23R variant. Moreover, the presence of cholesterol did not modify this behavior, and the β-sheet structural transitions were not registered when the N-terminal domain of hIAPP (K1-S20) was characterized. Considering that insulin granules are enriched in phosphatidylserine (PS), the property of lipid vesicles containing negatively charged lipids was also evaluated. We found that these types of lipids promote β-sheet conformational transitions in both the C-native segment and the new variants. Furthermore, these PS/peptides arrangements are internalized in Langerhans islet β-cells, localized in the endoplasmic reticulum, and trigger critical pathways such as unfolded protein response (UPR), affecting insulin secretion. Since this phenomenon was associated with the presence of cytotoxicity on Langerhans islet β-cells, it can be concluded that the anionic lipid environment and degree of solvation are critical conditions for the stability of segments with the propensity to form β-sheet structures, a situation that will eventually affect the structural characteristics and stability of IAPP within insulin granules, thus modifying the insulin secretion.
Cellular and Molecular Mechanism of Cardiac Regeneration: A Comparison of Newts, Zebrafish, and Mammals
Authors: de Wit Lousanne , Fang Juntao , Neef Klaus , Xiao Junjie , A. Doevendans Pieter , Schiffelers Raymond M. , Lei Zhiyong , Sluijter Joost P.G.
Published: August 2020

Cardiovascular disease is the leading cause of death worldwide. Current palliative treatments can slow the progression of heart failure, but ultimately, the only curative treatment for end-stage heart failure is heart transplantation, which is only available for a minority of patients due to lack of donors’ hearts. Explorative research has shown the replacement of the damaged and lost myocardium by inducing cardiac regeneration from preexisting myocardial cells. Lower vertebrates, such as the newt and zebrafish, can regenerate lost myocardium through cardiomyocyte proliferation. The preexisting adult cardiomyocytes replace the lost cells through subsequent dedifferentiation, proliferation, migration, and re-differentiation. Similarly, neonatal mice show complete cardiac regeneration post-injury; however, this regenerative capacity is remarkably diminished one week after birth. In contrast, the adult mammalian heart presents a fibrotic rather than a regenerative response and only shows signs of partial pathological cardiomyocyte dedifferentiation after injury. In this review, we explore the cellular and molecular responses to myocardial insults in different adult species to give insights for future interventional directions by which one can promote or activate cardiac regeneration in mammals.
Electrochemical Detection of Neurotransmitters
Authors: Banerjee Saikat , McCracken Stephanie , Hossain Md Faruk , Slaughter Gymama
Published: August 2020

Neurotransmitters are important chemical messengers in the nervous system that play a crucial role in physiological and physical health. Abnormal levels of neurotransmitters have been correlated with physical, psychotic, and neurodegenerative diseases such as Alzheimer’s, Parkinson’s, dementia, addiction, depression, and schizophrenia. Although multiple neurotechnological approaches have been reported in the literature, the detection and monitoring of neurotransmitters in the brain remains a challenge and continues to garner significant attention. Neurotechnology that provides high-throughput, as well as fast and specific quantification of target analytes in the brain, without negatively impacting the implanted region is highly desired for the monitoring of the complex intercommunication of neurotransmitters. Therefore, it is crucial to develop clinical assessment techniques that are sensitive and reliable to monitor and modulate these chemical messengers and screen diseases. This review focuses on summarizing the current electrochemical measurement techniques that are capable of sensing neurotransmitters with high temporal resolution in real time. Advanced neurotransmitter sensing platforms that integrate nanomaterials and biorecognition elements are explored.
A Preliminary Study on Cranio-Facial Characteristics Associated with Minor Neurological Dysfunctions (MNDs) in Children with Autism Spectrum Disorders (ASD)
Authors: Maniscalco Laura , Frédérique Bonnet-Brilhault , Roccella Michele , Matranga Domenica , Tripi Gabriele
Published: August 2020

Background. Craniofacial anomalies and minor neurological dysfunction (MNDs) have been identified, in literature, as risk factors for neurodevelopmental disorders. They represent physical indicators of embryonic development suggesting a possible contributory role of complications during early, even pre-conceptional, phases of ontogeny in autism spectrum disorders (ASD). Limited research has been conducted about the co-occurrence of the two biomarkers in children with ASD. This study investigates the associative patterns of cranio-facial anomalies and MNDs in ASD children, and whether these neurodevelopmental markers correlate with intensity of ASD symptoms and overall functioning. Methods. Caucasian children with ASD (n = 33) were examined. Measures were based on five anthropometric cranio-facial indexes and a standardized and detailed neurological examination according to Touwen. Relationships between anthropometric z-scores, MNDs and participant characteristics (i.e., age, cognitive abilities, severity of autistic symptoms measured using the Childhood Autism Rating Scale (CARS) checklist) were assessed. Results. With respect to specific MNDs, significant positive correlations were found between Cephalic Index and Sensory deficits (p-value < 0.001), which did not correlate with CARS score. Importantly, CARS score was positively linked with Intercanthal Index (p-value < 0.001), and negatively associated with posture and muscle tone (p-value = 0.027) and Facial Index (p-value = 0.004). Conclusion. Our data show a link between a specific facial phenotype and anomalies in motor responses, suggesting early brain dysmaturation involving subcortical structures in cerebro-craniofacial development of autistic children. This research supports the concept of a “social brain functional morphology” in autism spectrum disorders.
Expression of Dopamine-Related Genes in Four Human Brain Regions
Authors: Stanfill Ansley Grimes , Cao Xueyuan
Published: August 2020

A better understanding of dopaminergic gene expression will inform future treatment options for many different neurologic and psychiatric conditions. Here, we utilized the National Institutes of Health’s Genotype-Tissue Expression project (GTEx) dataset to investigate genotype by expression associations in seven dopamine pathway genes (ANKK1, DBH, DRD1, DRD2, DRD3, DRD5, and SLC6A3) in and across four human brain tissues (prefrontal cortex, nucleus accumbens, substantia nigra, and hippocampus). We found that age alters expression of DRD1 in the nucleus accumbens and prefrontal cortex, DRD3 in the nucleus accumbens, and DRD5 in the hippocampus and prefrontal cortex. Sex was associated with expression of DRD5 in substantia nigra and hippocampus, and SLC6A3 in substantia nigra. We found that three linkage disequilibrium blocks of SNPs, all located in DRD2, were associated with alterations in expression across all four tissues. These demographic characteristic associations and these variants should be further investigated for use in screening, diagnosis, and future treatment of neurological and psychiatric conditions.
Coordinated Human Brainstem and Spinal Cord Networks during the Expectation of Pain Have Elements Unique from Resting-State Effects
Authors: Ioachim Gabriela , Powers Jocelyn , Warren Howard , Stroman Patrick
Published: August 2020

Functional magnetic resonance imaging (fMRI) research on the human brainstem (BS) and spinal cord (SC) has identified extensive BS/SC resting-state networks (RSNs) by showing spontaneous coordinated blood oxygenation-level dependent (BOLD) signal fluctuations in the absence of a stimulus. Studies have shown that these networks can be influenced by participants’ level of arousal or attention (e.g., watching a video), and linked network function to autonomic homeostatic regulation. Here we explore how the cognitive state of expecting pain can influence connectivity in these networks. Data from two studies (a predictable pain stimulus study, and a resting-state study) were compared to show the effects of expecting pain on BS/SC networks, and how networks differed from networks associated with the resting-state. In each study, BOLD fMRI data were obtained from the cervical SC and brainstem in healthy participants at 3 tesla using a T2-weighted single-shot fast spin-echo imaging method. Functional connectivity was investigated within the entire 3D volume by means of structural equation modeling (SEM) and analyses of covariance (ANCOVA). Results showed extensive connectivity within/across BS and SC regions during the expectation of pain, and ANCOVA analyses showed that connectivity in specific components of these networks varied with individual pain sensitivity. Comparing these results to RSN fluctuations revealed commonalities in coordination between BS and SC regions, and specific BS–BS connectivity fluctuations unique to the expectation of pain. Based on the regions involved, these results provide evidence of brainstem regulation specific to the expectation of pain.
The FMS like Tyrosine Kinase 3 (FLT3) Is Overexpressed in a Subgroup of Multiple Myeloma Patients with Inferior Prognosis
Authors: Steiner Normann , Jöhrer Karin , Plewan Selina , Brunner-Véber Andrea , Göbel Georg , Nachbaur David , Wolf Dominik , Gunsilius Eberhard , Untergasser Gerold
Published: August 2020

Therapy resistance remains a major challenge in the management of multiple myeloma (MM). We evaluated the expression of FLT3 tyrosine kinase receptor (FLT3, CD135) in myeloma cells as a possible clonal driver. FLT3 expression was analyzed in bone marrow biopsies of patients with monoclonal gammopathy of undetermined significance or smoldering myeloma (MGUS, SMM), newly diagnosed MM (NDMM), and relapsed/refractory MM (RRMM) by immunohistochemistry (IHC). FLT3 gene expression was analyzed by RNA sequencing (RNAseq) and real-time PCR (rt-PCR). Anti-myeloma activity of FLT3 inhibitors (midostaurin, gilteritinib) was tested in vitro on MM cell lines and primary MM cells by 3H-tymidine incorporation assays or flow cytometry. Semi-quantitative expression analysis applying a staining score (FLT3 expression IHC-score, FES, range 1–6) revealed that a high FES (>3) was associated with a significantly shorter progression-free survival (PFS) in NDMM and RRMM patients (p = 0.04). RNAseq and real-time PCR confirmed the expression of FLT3 in CD138-purified MM samples. The functional relevance of FLT3 expression was corroborated by demonstrating the in vitro anti-myeloma activity of FLT3 inhibitors on FLT3-positive MM cell lines and primary MM cells. FLT3 inhibitors might offer a new targeted therapy approach in a subgroup of MM patients displaying aberrant FLT3 signaling.
P2X7 Receptor Promotes Mouse Mammary Cancer Cell Invasiveness and Tumour Progression, and Is a Target for Anticancer Treatment
Authors: Brisson Lucie , Chadet Stéphanie , Lopez-Charcas Osbaldo , Jelassi Bilel , Ternant David , Chamouton Julie , Lerondel Stéphanie , Le Pape Alain , Couillin Isabelle , Gombault Aurélie , Trovero Fabrice , Chevalier Stéphan , Besson Pierre , Jiang Lin-Hua , Roger Sébastien
Published: August 2020

The P2X7 receptor is an ATP-gated cation channel with a still ambiguous role in cancer progression, proposed to be either pro- or anti-cancerous, depending on the cancer or cell type in the tumour. Its role in mammary cancer progression is not yet defined. Here, we show that P2X7 receptor is functional in highly aggressive mammary cancer cells, and induces a change in cell morphology with fast F-actin reorganization and formation of filopodia, and promotes cancer cell invasiveness through both 2- and 3-dimensional extracellular matrices in vitro. Furthermore, P2X7 receptor sustains Cdc42 activity and the acquisition of a mesenchymal phenotype. In an immunocompetent mouse mammary cancer model, we reveal that the expression of P2X7 receptor in cancer cells, but not in the host mice, promotes tumour growth and metastasis development, which were reduced by treatment with specific P2X7 antagonists. Our results demonstrate that P2X7 receptor drives mammary tumour progression and represents a pertinent target for mammary cancer treatment.
Hypoxia Predicts Poor Prognosis in Neuroblastoma Patients and Associates with Biological Mechanisms Involved in Telomerase Activation and Tumor Microenvironment Reprogramming
Authors: Cangelosi Davide , Morini Martina , Zanardi Nicolò , Sementa Angela Rita , Muselli Marco , Conte Massimo , Garaventa Alberto , Pfeffer Ulrich , Bosco Maria Carla , Varesio Luigi , Eva Alessandra
Published: August 2020

The biological and clinical heterogeneity of neuroblastoma (NB) demands novel biomarkers and therapeutic targets in order to drive the most appropriate treatment for each patient. Hypoxia is a condition of low-oxygen tension occurring in poorly vascularized tumor tissues. In this study, we aimed to assess the role of hypoxia in the pathogenesis of NB and at developing a new clinically relevant hypoxia-based predictor of outcome. We analyzed the gene expression profiles of 1882 untreated NB primary tumors collected at diagnosis and belonging to four existing data sets. Analyses took advantage of machine learning methods. We identified NB-hop, a seven-gene hypoxia biomarker, as a predictor of NB patient prognosis, which is able to discriminate between two populations of patients with unfavorable or favorable outcome on a molecular basis. NB-hop retained its prognostic value in a multivariate model adjusted for established risk factors and was able to additionally stratify clinically relevant groups of patients. Tumors with an unfavorable NB-hop expression showed a significant association with telomerase activation and a hypoxic, immunosuppressive, poorly differentiated, and apoptosis-resistant tumor microenvironment. NB-hop defines a new population of NB patients with hypoxic tumors and unfavorable prognosis and it represents a critical factor for the stratification and treatment of NB patients.
Practical Review on Preclinical Human 3D Glioblastoma Models: Advances and Challenges for Clinical Translation
Authors: Soubéran Aurélie , Tchoghandjian Aurélie
Published: August 2020

Fifteen years after the establishment of the Stupp protocol as the standard of care to treat glioblastomas, no major clinical advances have been achieved and increasing patient’s overall survival remains a challenge. Nevertheless, crucial molecular and cellular findings revealed the intra-tumoral and inter-tumoral complexities of these incurable brain tumors, and the essential role played by cells of the microenvironment in the lack of treatment efficacy. Taking this knowledge into account, fulfilling gaps between preclinical models and clinical samples is necessary to improve the successful rate of clinical trials. Since the beginning of the characterization of brain tumors initiated by Bailey and Cushing in the 1920s, several glioblastoma models have been developed and improved. In this review, we focused on the most widely used 3D human glioblastoma models, including spheroids, tumorospheres, organotypic slices, explants, tumoroids and glioblastoma-derived from cerebral organoids. We discuss their history, development and especially their usefulness.
Biosynthesis of Putrescine from L-arginine Using Engineered Escherichia coli Whole Cells
Authors: Hui Hongjie , Bai Yajun , Fan Tai-Ping , Zheng Xiaohui , Cai Yujie
Published: August 2020

Putrescine, a biogenic amine, is a highly valued compound in medicine, industry, and agriculture. In this study, we report a whole-cell biocatalytic method in Escherichia coli for the production of putrescine, using L-arginine as the substrate. L-arginine decarboxylase and agmatine ureohydrolase were co-expressed to produce putrescine from L-arginine. Ten plasmids with different copy numbers and ordering of genes were constructed to balance the expression of the two enzymes, and the best strain was pACYCDuet-speB-speA. The optimal concentration of L-arginine was determined to be 20 mM for this strain. The optimum pH of the biotransformation was 9.5, and the optimum temperature was 45 °C; under these conditions, the yield of putrescine was 98%. This whole-cell biocatalytic method appeared to have great potential for the production of putrescine.
Correction: Yao, Y., et al. Activation of Slit2/Robo1 Signaling Promotes Tumor Metastasis in Colorectal Carcinoma through Activation of the TGF-β/Smads Pathway. Cells 2019, 8, 635
Authors: Yao Yuying , Zhou Zijun , Li Liuyou , Li Junchen , Huang Lixun , Li Jiangchao , Qi Cuiling , Zheng Lingyun , Wang Lijing , Zhang Qian-Qian
Published: August 2020

The author wishes to make the following correction to this paper [...]
5-aza-2′-Deoxycytidine Induces a RIG-I-Related Innate Immune Response by Modulating Mitochondria Stress in Neuroblastoma
Authors: Lin Hung-Yu , Chuang Jiin-Haur , Wang Pei-Wen , Lin Tsu-Kung , Wu Min-Tsui , Hsu Wen-Ming , Chuang Hui-Ching
Published: August 2020

Background: Neuroblastoma (NB) is one of the most common malignant solid tumors to occur in children, characterized by a wide range of genetic and epigenetic aberrations. We studied whether modifications of the latter with a 5-aza-2′-deoxycytidine (decitabine, Dac) DNA methyltransferase inhibitor can provide a therapeutic advantage in NB. Methods: NB cells with or without MYCN amplification were treated with Dac. We used flow cytometry to measure cell apoptosis and death and mitochondrial reactive oxygen species (mtROS), microarray to analyze gene expression profile and bisulfite pyrosequencing to determine the methylation level of the DDX58/RIG-I promoter. Western blot was used to detect markers related to innate immune response and apoptotic signaling, while immunofluorescent imaging was used to determine dsRNA. We generated mtDNA depleted ρ0 cells using long-term exposure to low-dose ethidium bromide. Results: Dac preferentially induced a RIG-I-predominant innate immune response and cell apoptosis in SK-N-AS NB cells, significantly reduced the methylation level of the DDX58/RIG-I promoter and increased dsRNA accumulation in the cytosol. Dac down regulated mitochondrial genes related to redox homeostasis, but augmented mtROS production. ρ0 cells demonstrated a blunted response in innate immune response and apoptotic cell death, as well as greatly diminished dsRNA. The response of NB cells to CDDP and poly(I:C) was potentiated by Dac in association with increased mtROS, which was blunted in ρ0 cells. Conclusions: This study indicates that Dac effectively induces a RIG-I-related innate immune response and apoptotic signaling primarily in SK-N-AS NB cells by hypomethylating DDX58/RIG-I promoter, elevated mtROS and increased dsRNA. Dac can potentiate the cytotoxic effects of CDDP and poly(I:C) in NB cells.
The Effectiveness of Hippotherapy to Recover Gross Motor Function in Children with Cerebral Palsy: A Systematic Review and Meta-Analysis
Authors: Guindos-Sanchez Laura , Lucena-Anton David , Moral-Munoz Jose , Salazar Alejandro , Carmona-Barrientos Ines
Published: August 2020

Cerebral palsy (CP) is a permanent disorder of the posture and movement, which can result in impairments of gross motor function, among others. Hippotherapy (HPT) is an emerging intervention to promote motor recovery in patients with neurological disorders, providing a smooth, precise, rhythmic, and repetitive pattern of movement to the patient. The main objective of this systematic review and meta-analysis of randomized controlled clinical trials was to analyze the effectiveness of HPT interventions on gross motor function in subjects with CP. The following databases were searched in May 2019: PubMed, Scopus, Embase, and Web of Science. The methodological quality of the randomized controlled trials was assessed using the Physiotherapy Evidence Database (PEDro) scale. A total of 10 studies were analyzed in this review, involving 452 participants. Favorable effects were obtained on the gross motor function (Gross Motor Function Measure-66, standardized mean difference (SMD) = 0.81, 95% confidence interval (CI) = 0.47–1.15, Gross Motor Function Measure-88 dimension A SMD = 0.64, 95% CI = 0.30–0.97, dimension B SMD = 0.42, 95% CI = 0.09–0.75, and dimension E SMD = 0.40, 95% CI = 0.06–0.73). The results obtained in the present review show the potential benefit of HPT intervention in improving gross motor function in children with CP.