bluuebunny/crossref_metadata_2025 huggingface dataset:
Genetic Landscape of Common Epilepsies: Advancing towards Precision in Treatment
Authors: Thakran Sarita , Guin Debleena , Singh Pooja , Singh Priyanka , Kukal Samiksha , Rawat Chitra , Yadav Saroj , Kushwaha Suman S. , Srivastava Achal K. , Hasija Yasha , Saso Luciano , Ramachandran Srinivasan , Kukreti Ritushree
Published: October 2020

Epilepsy, a neurological disease characterized by recurrent seizures, is highly heterogeneous in nature. Based on the prevalence, epilepsy is classified into two types: common and rare epilepsies. Common epilepsies affecting nearly 95% people with epilepsy, comprise generalized epilepsy which encompass idiopathic generalized epilepsy like childhood absence epilepsy, juvenile myoclonic epilepsy, juvenile absence epilepsy and epilepsy with generalized tonic-clonic seizure on awakening and focal epilepsy like temporal lobe epilepsy and cryptogenic focal epilepsy. In 70% of the epilepsy cases, genetic factors are responsible either as single genetic variant in rare epilepsies or multiple genetic variants acting along with different environmental factors as in common epilepsies. Genetic testing and precision treatment have been developed for a few rare epilepsies and is lacking for common epilepsies due to their complex nature of inheritance. Precision medicine for common epilepsies require a panoramic approach that incorporates polygenic background and other non-genetic factors like microbiome, diet, age at disease onset, optimal time for treatment and other lifestyle factors which influence seizure threshold. This review aims to comprehensively present a state-of-art review of all the genes and their genetic variants that are associated with all common epilepsy subtypes. It also encompasses the basis of these genes in the epileptogenesis. Here, we discussed the current status of the common epilepsy genetics and address the clinical application so far on evidence-based markers in prognosis, diagnosis, and treatment management. In addition, we assessed the diagnostic predictability of a few genetic markers used for disease risk prediction in individuals. A combination of deeper endo-phenotyping including pharmaco-response data, electro-clinical imaging, and other clinical measurements along with genetics may be used to diagnose common epilepsies and this marks a step ahead in precision medicine in common epilepsies management.
Mutation of Arabidopsis Copper-Containing Amine Oxidase Gene AtCuAOδ Alters Polyamines, Reduces Gibberellin Content and Affects Development
Authors: Alharbi Basmah , Hunt Julie D. , Dimitrova Simone , Spadafora Natasha D. , Cort Alex P. , Colombo Davide , Müller Carsten T. , Ghuge Sandip A. , Davoli Daniela , Cona Alessandra , Mariotti Lorenzo , Picciarelli Piero , de Graaf Barend , Rogers Hilary J.
Published: October 2020

Polyamines (PAs) are essential metabolites in plants performing multiple functions during growth and development. Copper-containing amine oxidases (CuAOs) catalyse the catabolism of PAs and in Arabidopsis thaliana are encoded by a gene family. Two mutants of one gene family member, AtCuAOδ, showed delayed seed germination, leaf emergence, and flowering time. The height of the primary inflorescence shoot was reduced, and developmental leaf senescence was delayed. Siliques were significantly longer in mutant lines and contained more seeds. The phenotype of AtCuAOδ over-expressors was less affected. Before flowering, there was a significant increase in putrescine in AtCuAOδ mutant leaves compared to wild type (WT), while after flowering both spermidine and spermine concentrations were significantly higher than in WT leaves. The expression of GA (gibberellic acid) biosynthetic genes was repressed and the content of GA1, GA7, GA8, GA9, and GA20 was reduced in the mutants. The inhibitor of copper-containing amine oxidases, aminoguanidine hydrochloride, mimicked the effect of AtCuAOδ mutation on WT seed germination. Delayed germination, reduced shoot height, and delayed flowering in the mutants were rescued by GA3 treatment. These data strongly suggest AtCuAOδ is an important gene regulating PA homeostasis, and that a perturbation of PAs affects plant development through a reduction in GA biosynthesis.
An Overview of ADAM9: Structure, Activation, and Regulation in Human Diseases
Authors: Chou Cheng-Wei , Huang Yu-Kai , Kuo Ting-Ting , Liu Jing-Pei , Sher Yuh-Pyng
Published: October 2020

ADAM9 (A disintegrin and a metalloprotease 9) is a membrane-anchored protein that participates in a variety of physiological functions, primarily through the disintegrin domain for adhesion and the metalloprotease domain for ectodomain shedding of a wide variety of cell surface proteins. ADAM9 influences the developmental process, inflammation, and degenerative diseases. Recently, increasing evidence has shown that ADAM9 plays an important role in tumor biology. Overexpression of ADAM9 has been found in several cancer types and is correlated with tumor aggressiveness and poor prognosis. In addition, through either proteolytic or non-proteolytic pathways, ADAM9 promotes tumor progression, therapeutic resistance, and metastasis of cancers. Therefore, comprehensively understanding the mechanism of ADAM9 is crucial for the development of therapeutic anti-cancer strategies. In this review, we summarize the current understanding of ADAM9 in biological function, pathophysiological diseases, and various cancers. Recent advances in therapeutic strategies using ADAM9-related pathways are presented as well.
Calcium Modulation, Anti-Oxidant and Anti-Inflammatory Effect of Skin Allergens Targeting the Nrf2 Signaling Pathway in Alzheimer’s Disease Cellular Models
Authors: Silva Ana , Pereira Marta , Carrascal Mylène A. , Brites Gonçalo , Neves Bruno , Moreira Patrícia , Resende Rosa , Silva Maria Manuel , Santos Armanda E. , Pereira Cláudia , Cruz Maria Teresa
Published: October 2020

Experimental evidence highlights nuclear factor (erythroid-derived 2)-like 2 (Nrf2) as a molecular target in Alzheimer’s disease (AD). The well-known effect of electrophilic cysteine-reactive skin allergens on Nrf2-activation led to the hypothesis that these compounds could have a therapeutic role in AD. This was further supported by the neuroprotective activity of the skin allergen dimethyl fumarate (DMF), demonstrated in in vivo models of neurodegenerative diseases. We evaluated the effect of the cysteine-reactive allergens 1,4-phenylenediamine (PPD) and methyl heptine carbonate (MHC) on (1) neuronal redox imbalance and calcium dyshomeostasis using N2a wild-type (N2a-wt) and human APP-overexpressing neuronal cells (wild-type, N2a-APPwt) and (2) on neuroinflammation, using microglia BV-2 cells exposed to LPS (lipopolysaccharide). Phthalic anhydride (PA, mainly lysine-reactive), was used as a negative control. DMF, PPD and MHC increased Hmox1 gene and HMOX1 protein levels in N2a-APPwt cells suggesting Nrf2-dependent antioxidant activity. MHC, but also PA, rescued N2a-APPwt mitochondrial membrane potential and calcium levels in a Nrf2-independent pathway. All the chemicals showed anti-inflammatory activity by decreasing iNOS protein in microglia. This work highlights the potential neuroprotective and anti-inflammatory role of the selected skin allergens in in vitro models of AD, and supports further studies envisaging the validation of the results using in vivo AD models.
Newly Synthesized Imino-Derivatives Analogues of Resveratrol Exert Inhibitory Effects in Breast Tumor Cells
Authors: Iacopetta Domenico , Lappano Rosamaria , Mariconda Annaluisa , Ceramella Jessica , Sinicropi Maria Stefania , Saturnino Carmela , Talia Marianna , Cirillo Francesca , Martinelli Fabio , Puoci Francesco , Rosano Camillo , Longo Pasquale , Maggiolini Marcello
Published: October 2020

Breast cancer represents the most frequently diagnosed malignancy in women worldwide. Various therapeutics are currently used in order to halt the progression of breast tumor, even though certain side effects may limit the beneficial effects. In recent years, many efforts have been addressed to the usefulness of natural compounds as anticancer agents due to their low toxicity. Resveratrol, a stilbene found in grapes, berries, peanuts and soybeans, has raised a notable interest for its antioxidant, anti-inflammatory, and antitumor properties. Here, we report the design, the synthesis and the characterization of the anticancer activity of a small series of imino N-aryl-substituted compounds that are analogues of resveratrol. In particular, the most active compound, named 3, exhibited anti-tumor activity in diverse types of breast cancer cells through the inhibition of the human topoisomerase II and the induction of apoptotic cell death. Therefore, the abovementioned compound maybe considered as a promising agent in more comprehensive treatments of breast cancer.
Advanced Methods for Studying Structure and Interactions of Macrolide Antibiotics
Authors: Jednačak Tomislav , Mikulandra Ivana , Novak Predrag
Published: October 2020

Macrolide antibiotics are macrocyclic compounds that are clinically used and prescribed for the treatment of upper and lower respiratory tract infections. They inhibit the synthesis of bacterial proteins by reversible binding to the 23S rRNA at or near the peptidyl transferase center. However, their excellent antibacterial profile was largely compromised by the emergence of bacterial resistance. Today, fighting resistance to antibiotics is one of the greatest challenges in medicinal chemistry. Considering various physicochemical properties of macrolides, understanding their structure and interactions with macromolecular targets is crucial for the design of new antibiotics efficient against resistant pathogens. The solid-state structures of some macrolide-ribosome complexes have recently been solved, throwing new light on the macrolide binding mechanisms. On the other hand, a combination of NMR spectroscopy and molecular modeling calculations can be applied to study free and bound conformations in solution. In this article, a description of advanced physicochemical methods for elucidating the structure and interactions of macrolide antibiotics in solid state and solution will be provided, and their principal advantages and drawbacks will be discussed.
Intranasal Administration of Mesenchymal Stem Cell Secretome Reduces Hippocampal Oxidative Stress, Neuroinflammation and Cell Death, Improving the Behavioral Outcome Following Perinatal Asphyxia
Authors: Farfán Nancy , Carril Jaime , Redel Martina , Zamorano Marta , Araya Maureen , Monzón Estephania , Alvarado Raúl , Contreras Norton , Tapia-Bustos Andrea , Quintanilla María Elena , Ezquer Fernando , Valdés José Luis , Israel Yedy , Herrera-Marschitz Mario , Morales Paola
Published: October 2020

Perinatal Asphyxia (PA) is a leading cause of motor and neuropsychiatric disability associated with sustained oxidative stress, neuroinflammation, and cell death, affecting brain development. Based on a rat model of global PA, we investigated the neuroprotective effect of intranasally administered secretome, derived from human adipose mesenchymal stem cells (MSC-S), preconditioned with either deferoxamine (an hypoxia-mimetic) or TNF-α+IFN-γ (pro-inflammatory cytokines). PA was generated by immersing fetus-containing uterine horns in a water bath at 37 °C for 21 min. Thereafter, 16 μL of MSC-S (containing 6 μg of protein derived from 2 × 105 preconditioned-MSC), or vehicle, were intranasally administered 2 h after birth to asphyxia-exposed and control rats, evaluated at postnatal day (P) 7. Alternatively, pups received a dose of either preconditioned MSC-S or vehicle, both at 2 h and P7, and were evaluated at P14, P30, and P60. The preconditioned MSC-S treatment (i) reversed asphyxia-induced oxidative stress in the hippocampus (oxidized/reduced glutathione); (ii) increased antioxidative Nuclear Erythroid 2-Related Factor 2 (NRF2) translocation; (iii) increased NQO1 antioxidant protein; (iv) reduced neuroinflammation (decreasing nuclearNF-κB/p65 levels and microglial reactivity); (v) decreased cleaved-caspase-3 cell-death; (vi) improved righting reflex, negative geotaxis, cliff aversion, locomotor activity, anxiety, motor coordination, and recognition memory. Overall, the study demonstrates that intranasal administration of preconditioned MSC-S is a novel therapeutic strategy that prevents the long-term effects of perinatal asphyxia.
Shear Stress-Induced Activation of von Willebrand Factor and Cardiovascular Pathology
Authors: Okhota Sergey , Melnikov Ivan , Avtaeva Yuliya , Kozlov Sergey , Gabbasov Zufar
Published: October 2020

The von Willebrand factor (vWF) is a plasma protein that mediates platelet adhesion and leukocyte recruitment to vascular injury sites and carries coagulation factor VIII, a building block of the intrinsic pathway of coagulation. The presence of ultra-large multimers of vWF in the bloodstream is associated with spontaneous thrombosis, whereas its deficiency leads to bleeding. In cardiovascular pathology, the progression of the heart valve disease results in vWF deficiency and cryptogenic gastrointestinal bleeding. The association between higher plasma levels of vWF and thrombotic complications of coronary artery disease was described. Of note, it is not the plasma levels that are crucial for vWF hemostatic activity, but vWF activation, triggered by a rise in shear rates. vWF becomes highly reactive with platelets upon unfolding into a stretched conformation, at shear rates above the critical value (more than 5000 s−1), which might occur at sites of arterial stenosis and injury. The activation of vWF and its counterbalance by ADAMTS-13, the vWF-cleaving protease, might contribute to complications of cardiovascular diseases. In this review, we discuss vWF involvement in complications of cardiovascular diseases and possible diagnostic and treatment approaches.
Data-Driven Critical Tract Variable Determination for European Portuguese
Authors: Silva Samuel , Almeida Nuno , Cunha Conceição , Joseph Arun , Frahm Jens , Teixeira António
Published: October 2020

Technologies, such as real-time magnetic resonance (RT-MRI), can provide valuable information to evolve our understanding of the static and dynamic aspects of speech by contributing to the determination of which articulators are essential (critical) in producing specific sounds and how (gestures). While a visual analysis and comparison of imaging data or vocal tract profiles can already provide relevant findings, the sheer amount of available data demands and can strongly profit from unsupervised data-driven approaches. Recent work, in this regard, has asserted the possibility of determining critical articulators from RT-MRI data by considering a representation of vocal tract configurations based on landmarks placed on the tongue, lips, and velum, yielding meaningful results for European Portuguese (EP). Advancing this previous work to obtain a characterization of EP sounds grounded on Articulatory Phonology, important to explore critical gestures and advance, for example, articulatory speech synthesis, entails the consideration of a novel set of tract variables. To this end, this article explores critical variable determination considering a vocal tract representation aligned with Articulatory Phonology and the Task Dynamics framework. The overall results, obtained considering data for three EP speakers, show the applicability of this approach and are consistent with existing descriptions of EP sounds.
TITUS: Visualization of Neutrino Events in Liquid Argon Time Projection Chambers
Authors: Adams Corey , del Tutto Marco
Published: October 2020

The amount and complexity of data recorded by high energy physics experiments are rapidly growing, and with these grow the difficulties in visualizing such data. To study the physics of neutrinos, a type of elementary particle, scientists use liquid argon time projection chamber (LArTPC) detectors, among other technologies. LArTPCs have a very high spatial resolution and resolve many of the elementary particles that come out of a neutrino interacting within the argon in the detector. Visualizing these neutrino interactions is of fundamental importance to understanding the properties of neutrinos, but also monitoring and checking on the detector conditions and operations. From these ideas, we have developed TITUS, an event display that shows images recorded by these neutrino detectors. TITUS is a piece of software that reads data coming from LArTPC detectors (as well as the corresponding simulation) and allows users to explore such data in multiple ways. TITUS is flexible to enable fast prototyping and customization.
Fabrication and Characterisation of Aligned Discontinuous Carbon Fibre Reinforced Thermoplastics as Feedstock Material for Fused Filament Fabrication
Authors: Blok Lourens , Longana Marco , Woods Benjamin
Published: October 2020

In this work, aligned discontinuous fibre composite (ADFRC) tapes were developed and investigated as precursors for a novel 3D printing filament. ADFRCs have the potential to achieve mechanical performance comparable to continuous fibre reinforced composites, given sufficient fibre length and high level of alignment, and avoid many of the manufacturing difficulties associated with continuous fibres, e.g., wrinkling, bridging and corner radii constraints. Their potential use for fused filament fabrication (FFF) techniques was investigated here. An extensive down-selection process of thermoplastic matrices was performed, as matrix properties significantly impact both the processing and performance of the filament. This resulted in four candidate polymers (ABS, PLA, Nylon, PETG) which were used to manufacture ADFRC tapes with a Vf of 12.5% using the high performance discontinuous fibre (HiPerDiF) technology and an in-house developed continuous consolidation module. Tensile stiffness and strength up to 30 GPa and 400 MPa respectively were recorded, showing that a discontinuous fibre filament has the potential to compete with continuous fibre filaments.
Experimental Determination of the Manson−Coffin Curves for an Original Unconventional Vehicle Frame
Authors: Sága Milan , Blatnický Miroslav , Vaško Milan , Dižo Ján , Kopas Peter , Gerlici Juraj
Published: October 2020

This article is divided into two parts—in the first part, authors inform about their testing device that enables the acquisition of results from uniaxial and multiaxial fatigue tests (the bending−torsion combination). We present the approaches used during designing and building the testing device. The direct implementation of the research in the second part will concentrate on implementing the acquired results for the frame design of a vehicle worked out by the authors. The three-wheeled vehicle has the front steered wheel suspended in an unconventional way. This original design can cause an increased load on the vehicle’s frame. This can be apparent mainly during driving through curves. Therefore, the fatigue curves of the tested material (EN AW 6063) will be implemented from the point of view of its usability in operation. A vehicle frame is most often loaded by bending and torsion. The authors assess the influence of welding on the fatigue life of this unique unconventional vehicle by determining the fatigue curves of the material for its production. The stresses achieved on the test specimens fully correspond to the load of the frame (in welds) during its operation.
Large-Beam Picosecond Interference Patterning of Metallic Substrates
Authors: Hauschwitz Petr , Jochcová Dominika , Jagdheesh Radhakrishnan , Cimrman Martin , Brajer Jan , Rostohar Danijela , Mocek Tomáš , Kopeček Jaromír , Lucianetti Antonio , Smrž Martin
Published: October 2020

In this paper, we introduce a method to efficiently use a high-energy pulsed 1.7 ps HiLASE Perla laser system for two beam interference patterning. The newly developed method of large-beam interference patterning permits the production of micro and sub-micron sized features on a treated surface with increased processing throughputs by enlarging the interference area. The limits for beam enlarging are explained and calculated for the used laser source. The formation of a variety of surface micro and nanostructures and their combinations are reported on stainless steel, invar, and tungsten with the maximum fabrication speed of 206 cm2/min. The wettability of selected hierarchical structures combining interference patterns with 2.6 µm periodicity and the nanoscale surface structures on top were analyzed showing superhydrophobic behavior with contact angles of 164°, 156°, and 150° in the case of stainless steel, invar, and tungsten, respectively.
Dry Rolling/Sliding Wear of Bainitic Rail Steels under Different Contact Stresses and Slip Ratios
Authors: Liu Jiapeng , Li Yingqi , Zhang Yinhua , Hu Yue , Shi Lubing , Ding Haohao , Wang Wenjian , Liu Fengshou , Zhou Shaobo , Shi Tong
Published: October 2020

This study aims to deeply understand the effect of contact stress and slip ratio on wear performances of bainitic rail steels. The results showed that the wear loss increased as the contact stress and slip ratio increased. Based on the surface damage morphology and microstructural analyses, it revealed that the rolling contact fatigue wear mechanism played a significant role under the low slip ratio, but the dominant wear mechanism transferred to the abrasive wear at the high slip ratio. Meanwhile, the bainitic steel specifically presented worse wear resistance under the abrasive wear mode. Compared with the influence of a slip ratio, the increase in contact stress led to severer plastic flows and contributed to the propagation of cracks. In addition, the contact stress and slip ratio had the opposite effect on the friction coefficient, that is, the friction coefficient of bainitic steels behaved the inverse proportion with the contact stress, but positive proportion with the slip ratio. At last, the increase in slip ratio had more significant effect on the reduction of retained austenite (RA) than the enlargement of contact stress due to the fact that the RA would probably be removed before the martensitic transformation occurred under the abrasive wear mechanism.
Simvastatin Induces In Vitro Mineralization Effects of Primary Human Odontoblast-Like Cells
Authors: Sabandal Martin Mariano Isabelo , Schäfer Edgar , Imper Jessica , Jung Susanne , Kleinheinz Johannes , Sielker Sonja
Published: October 2020

Simvastatin (SV) is an often prescribed statin reducing the LDL-concentration in circulating blood. The aim of this study was to evaluate the pleiotropic effects of SV to primary human odontoblast-like cells. Twenty four wisdom teeth of different subjects were extracted and the pulp tissue was removed and minced under sterile conditions. After mincing, the requested cells were passaged according to established protocols. Osteoblastic marker (ALP conversion), viability and mineralization were determined at days 14, 17 and 21 after simvastatin exposition (0.01 µM, 0.1 µM, 1.0 µM, 2.0 µM). The sample size per group was 24 cultures with three replicates per culture for ALP-conversion and mineralization and 6 replicates for viability. A Kruskal–Wallis test was used for statistical analysis. After adding SV, viability was significantly (p < 0.01) decreased in a time- and dose-dependent manner, whereas after 21 days, mineralization was significant (p < 0.01). ALP-conversion in groups with SV concentrations of 1 and 2 µM SV was significantly (p < 0.01) increased. Pleiotropic effects regarding mineralization in higher SV concentrations were possibly induced via alternative mineralization pathways as almost equal elevations of ALP conversion were not evident in the control and experimental groups.
The Effects of Hybridisation of Composites Consisting of Aramid, Carbon, and Hemp Fibres in a Quasi-Static Penetration Test
Authors: Pach Joanna , Frączek Natalia , Kaczmar Jacek
Published: October 2020

The quasi-static penetration properties of hybrid laminates were experimentally investigated. Aramid fabrics, carbon fabrics, and short hemp fibres were applied as the reinforcements of hybrid and non-hybrid composite laminates with polyurethane–polyurea (PUR/PUA) matrix. The laminates were made by hand, in a mould. They were cured at room temperature for 24 h. Hybrid laminates consisted of aramid and carbon layers in two different configurations, i.e., aramid at the innermost layers and outermost layers. Aramid/PUR/PUA and carbon/PUR/PUA composites were fabricated for comparison purposes. Laminates were also prepared via an analogue sequence of laying the reinforcement layers with the addition of 5% by weight of hemp fibres in the PUR/PUA matrix. Quasi-static penetration tests (QSPT) were conducted using a tensile testing machine with a surface-hardened, hemispherical, steel punch (9 mm diameter tip), reflecting the geometry of the Parabellum projectile. A quasi-static puncture test was carried out until the laminate was perforated. The ratio between the support span (Ds) and the punch diameter (Dp) was SPR = Ds/Dp = 5.0. The results showed the influences of laminate hybridisation on the values of absorbed energy, punch shear strength, and damage mechanism in the QSPT test. The addition of hemp fibres to aramid laminates resulted in a positive hybridisation effect. The order of layers of aramid and carbon fabrics in hybrid laminates influenced the results obtained in the QSPT test.
Morphological, Chemical, and Biological Investigation of Ionic Substituted, Pulse Current Deposited Calcium Phosphate Coatings
Authors: Furko Monika , Balázsi Csaba
Published: October 2020

Ionic substituted calcium phosphate coatings (iCP) have been prepared by the electrochemical pulse current deposition technique with an alternate pulse on and off time of 5 ms onto a titanium alloy substrate. The elemental distribution and morphology of the deposited layers have been extensively studied by scanning electron microscopy (SEM), energy dispersive X-ray analysis (EDX), and transmission electron microscopy (TEM). The crystallinity and phase structure of iCPs have been investigated by X-ray diffraction (XRD). The corrosion characteristics and biodegradability of coatings have been determined by electrochemical measurements, recording potentiodynamic curves in a physiological solution over a long-term immersion period. The cell viability tests confirmed that the iCP coating was biocompatible, while the corrosion tests proved its biodegradable characteristic. In our paper, we compare the morphological, chemical, and biological characteristics of silver and zinc substituted calcium phosphate layers deposited by the electrochemical method.
Effect of the Drying Method of Pine and Beech Wood on Fracture Toughness and Shear Yield Stress
Authors: Chuchala Daniel , Sandak Jakub , Orlowski Kazimierz A. , Muzinski Tomasz , Lackowski Marcin , Ochrymiuk Tomasz
Published: October 2020

The modern wood converting processes consists of several stages and material drying belongs to the most influencing future performances of products. The procedure of drying wood is usually realized between subsequent sawing operations, affecting significantly cutting conditions and general properties of material. An alternative methodology for determination of mechanical properties (fracture toughness and shear yield stress) based on cutting process analysis is presented here. Two wood species (pine and beech) representing soft and hard woods were investigated with respect to four diverse drying methods used in industry. Fracture toughness and shear yield stress were determined directly from the cutting power signal that was recorded while frame sawing. An original procedure for compensation of the wood density variation is proposed to generalize mechanical properties of wood and allow direct comparison between species and drying methods. Noticeable differences of fracture toughness and shear yield stress values were found among all drying techniques and for both species, but only for beech wood the differences were statistically significant. These observations provide a new highlight on the understanding of the effect of thermo-hydro modification of wood on mechanical performance of structures. It can be also highly useful to optimize woodworking machines by properly adjusting cutting power requirements.
Antibacterial Activity of Chromomycins from a Marine-Derived Streptomyces microflavus
Authors: Cho Eunji , Kwon Oh-Seok , Chung Beomkoo , Lee Jayho , Sun Jeongyoon , Shin Jongheon , Oh Ki-Bong
Published: October 2020

A marine-derived actinomycete (Streptomyces sp. MBTI36) exhibiting antibacterial activities was investigated in the present study. The strain was identified using genetic techniques. The 16S rDNA sequence of the isolate indicated that it was most closely related to Streptomyces microflavus. Furthermore, a new chromomycin A9 (1), along with chromomycin Ap (2), chromomycin A2 (3), and chromomycin A3 (4), were isolated from the ethyl acetate extract. Their structures were determined using extensive spectroscopic methods including 1D and 2D NMR, and HRMS, as well as comparisons with previously reported data. Compounds 1–4 showed potent antibacterial activities against Gram-positive bacteria including methicillin-resistant Staphylococcus aureus (MRSA). During a passage experiment, minimum inhibitory concentration (MIC) values for compounds 1–4 showed no more than a 4-fold increase from the starting MIC value, indicating that no resistance was detected over the 21 passages.
Evaluation of Different Positive End-Expiratory Pressures Using Supreme™ Airway Laryngeal Mask during Minor Surgical Procedures in Children
Authors: Fiedler Mascha O. , Schätzle Elisabeth , Contzen Marius , Gernoth Christian , Weiß Christel , Walter Thomas , Viergutz Tim , Kalenka Armin
Published: October 2020

Background and objectives: The laryngeal mask is the method of choice for airway management in children during minor surgical procedures. There is a paucity of data regarding optimal management of mechanical ventilation in these patients. The Supreme™ airway laryngeal mask offers the option to insert a gastric tube to empty the stomach contents of air and/or gastric juice. The aim of this investigation was to evaluate the impact of positive end-expiratory positive pressure (PEEP) levels on ventilation parameters and gastric air insufflation during general anesthesia in children using pressure-controlled ventilation with laryngeal mask. Materials and Methods: An observational trial was carried out in 67 children aged between 1 and 11 years. PEEP levels of 0, 3 and 5 mbar were tested for 5 min in each patient during surgery and compared with ventilation parameters (dynamic compliance (mL/cmH2O), etCO2 (mmHg), peak pressure (mbar), tidal volume (mL), respiratory rate (per minute), FiO2 and gastric air (mL)) were measured at each PEEP. Air was aspirated from the stomach at the start of the sequence of measurements and at the end. Results: Significant differences were observed for the ventilation parameters: dynamic compliance (PEEP 5 vs. PEEP 3: p < 0.0001, PEEP 5 vs. PEEP 0: p < 0.0001, PEEP 3 vs. PEEP 0: p < 0.0001), peak pressure (PEEP 5 vs. PEEP 3: p < 0.0001, PEEP 5 vs. PEEP 0: p < 0.0001, PEEP 3 vs. PEEP 0: p < 0.0001) and tidal volume (PEEP 5 vs. PEEP 3: p = 0.0048, PEEP 5 vs. PEEP 0: p < 0.0001, PEEP 3 vs. PEEP 0: p < 0.0001). All parameters increased significantly with higher PEEP, with the exception of etCO2 (significant decrease) and respiratory rate (no significant difference). We also showed different values for air quantity in the comparisons between the different PEEP levels (PEEP 5: 2.8 ± 3.9 mL, PEEP 3: 1.8 ± 3.0 mL; PEEP 0: 1.6 ± 2.3 mL) with significant differences between PEEP 5 and PEEP 3 (p = 0.0269) and PEEP 5 and PEEP 0 (p = 0.0209). Conclusions: Our data suggest that ventilation with a PEEP of 5 mbar might be more lung protective in children using the Supreme™ airway laryngeal mask, although gastric air insufflation increased with higher PEEP. We recommend the use of a laryngeal mask with the option of inserting a gastric tube to evacuate potential gastric air.
Ganglion Cell Layer Thinning in Alzheimer’s Disease
Authors: López-de-Eguileta Alicia , Cerveró Andrea , Ruiz de Sabando Ainara , Sánchez-Juan Pascual , Casado Alfonso
Published: October 2020

The main advantages of optical retinal imaging may allow researchers to achieve deeper analysis of retinal ganglion cells (GC) in vivo using optical coherence tomography (OCT). Using this device to elucidate the impact of Alzheimer’s disease (AD) on retinal health with the aim to identify a new AD biomarker, a large amount of studies has analyzed GC in different stages of the disease. Our review highlights recent knowledge into measuring retinal morphology in AD making distinctive between whether those studies included patients with clinical dementia stage or also mild cognitive impairment (MCI), which selection criteria were applied to diagnosed patients included, and which device of OCT was employed. Despite several differences, previous works found a significant thinning of GC layer in patients with AD and MCI. In the long term, an important future direction is to achieve a specific ocular biomarker with enough sensitivity to reveal preclinical AD disorder and to monitor progression.
Fast Fabrication of Complex Surficial Micro-Features Using Sequential Lithography and Jet Electrochemical Machining
Authors: Wu Ming , Kumar Saxena Krishna , Guo Zhongning , Qian Jun , Reynaerts Dominiek
Published: October 2020

This paper presents fabrication of complex surficial micro-features employing a cross-innovative hybrid process inspired from lithography and Jet-ECM. The process is referred here as mask electrolyte jet machining (MEJM). MEJM is a non-contact machining process which combines high resolution of lithography and greater flexibility of Jet-ECM. It is a non-contact process which can fabricate variety of microstructures on difficult-to-machine materials without need of expensive tooling. The presented work demonstrates the process performance of this technology by statistical analysis and multivariate kernel density estimation (KDE) based on probabilistic density function. Micro-letters are fabricated as an example of complex surficial structure comprising of multiple intersecting, straight and curved grooves. The processing response is characterized in terms of geometrical size, similarity ratio, and cumulative shape deviation. Experimental results demonstrated that micro letters with good repeatability (minimum SD of shape error ratio 0.297%) and shape accuracy (minimum shape error of 0.039%) can be fabricated with this technology. The results suggest MEJM could be a promising technology for batch manufacturing of surface microstructures with high productivity.
Ultrasonic Navigation for the Treatment of Medication-Related Jaw Osteonecrosis Involving the Inferior Alveolar Nerve: A Case Report and Protocol Review
Authors: Pellegrino Gerardo , Pavanelli Francesca , Ferri Agnese , Lizio Giuseppe , Parrulli Roberto , Marchetti Claudio
Published: October 2020

Dynamic navigation (DN) is a computer-guided technique employed in different surgical fields and recently adopted in dental implantology to improve the accuracy of dental implant insertion. Medication-related osteonecrosis of the jaws (MRONJ) often requires the surgical removal of the impaired, hard tissue, trying at the same time to spare the healthy tissue and the noble anatomical structures. A case of extensive bilateral medication-related osteonecrosis, with the symptomatic involvement of the right mandibular canal, was successfully resolved with the use of ultrasonic surgery associated with a dynamic navigation, in order to limit the invasiveness of the surgical approach improving its reliability and accuracy. The usefulness of this technology in the management of MRONJ can be considered in future clinical trials to confirm the advantages and standardize the technique.
EMI Shielding of the Hydrophobic, Flexible, Lightweight Carbonless Nano-Plate Composites
Authors: Raagulan Kanthasamy , Ghim Jin Soo , Braveenth Ramanaskanda , Jung Moon Jai , Lee Sang Bok , Chai Kyu Yun , Mi Kim Bo , Lee Joonsik
Published: October 2020

The cost-effective spray coated composite was successfully synthesis and characterized by scanning electron microscopy, X-ray photoelectron spectroscopy, Raman spectroscopy, and X-ray diffraction techniques. The one step synthetic strategy was used for the synthesis of nanoplates that have a crystalline nature. The composites are amorphous and hydrophobic with micron thickness (<400 μm). The maximum contact angle showed by composite is 132.65° and have wetting energy of −49.32 mN m−1, spreading coefficient −122.12 mN m−1, and work of adhesion 23.48 mN m−1. The minimum thickness of synthesized nanoplate is 3 nm while the maximum sheet resistance, resistivity, and electrical conductivity of the composites are 11.890 ohm sq−1, 0.4399 Ω.cm−1, and 8.967 S.cm−1, respectively. The cobalt nanoplate coated non-woven carbon fabric (CoFC) possesses excellent sheet resistance, hydrophobic nature, and EMI shielding efficiency of 99.99964%. The composite can block above 99.9913% of incident radiation (X band). Hence, the composite can be utilized in application areas such as medical clothes, mobile phones, automobiles, aerospace, and military equipment.
Dietary Short-Term Fiber Interventions in Arthritis Patients Increase Systemic SCFA Levels and Regulate Inflammation
Authors: Dürholz Kerstin , Hofmann Jörg , Iljazovic Aida , Häger Julian , Lucas Sébastien , Sarter Kerstin , Strowig Till , Bang Holger , Rech Jürgen , Schett Georg , Zaiss Mario M.
Published: October 2020

Chronic inflammatory diseases are often initiated and guided by the release of proinflammatory mediators. Rheumatoid arthritis (RA) is caused by an imbalance between the pro- and anti-inflammatory mediators in the joints, thereby favoring chronic inflammation and joint damage. Here, we investigate if short-term high-fiber dietary intervention shifts this towards anti-inflammatory mediators. Healthy controls (n = 10) and RA patients (n = 29) under routine care received daily high-fiber bars for 15 or 30 days, respectively. Stool and sera were analyzed for pro- and anti-inflammatory mediators. A high-fiber dietary intervention resulted in increased anti-inflammatory short-chain fatty acids (SCFA), decreased proarthritic cytokine concentrations, along with a durable shift in the Firmicutes-to-Bacteroidetes ratio. Together, these results further strengthen high-fiber dietary interventions as a practical approach complementing existing pharmacological therapies.
The Impact of Amino Acids on Postprandial Glucose and Insulin Kinetics in Humans: A Quantitative Overview
Authors: van Sloun Bart , Goossens Gijs , Erdos Balazs , Lenz Michael , van Riel Natal , Arts Ilja
Published: October 2020

Different amino acids (AAs) may exert distinct effects on postprandial glucose and insulin concentrations. A quantitative comparison of the effects of AAs on glucose and insulin kinetics in humans is currently lacking. PubMed was queried to identify intervention studies reporting glucose and insulin concentrations after acute ingestion and/or intravenous infusion of AAs in healthy adults and those living with obesity and/or type 2 diabetes (T2DM). The systematic literature search identified 55 studies that examined the effects of l-leucine, l-isoleucine, l-alanine, l-glutamine, l-arginine, l-lysine, glycine, l-proline, l-phenylalanine, l-glutamate, branched-chain AAs (i.e., l-leucine, l-isoleucine, and l-valine), and multiple individual l-AAs on glucose and insulin concentrations. Oral ingestion of most individual AAs induced an insulin response, but did not alter glucose concentrations in healthy participants. Specific AAs (i.e., leucine and isoleucine) co-ingested with glucose exerted a synergistic effect on the postprandial insulin response and attenuated the glucose response compared to glucose intake alone in healthy participants. Oral AA ingestion as well as intravenous AA infusion was able to stimulate an insulin response and decrease glucose concentrations in T2DM and obese individuals. The extracted information is publicly available and can serve multiple purposes such as computational modeling.
Does the Energy Restriction Intermittent Fasting Diet Alleviate Metabolic Syndrome Biomarkers? A Randomized Controlled Trial
Authors: Kunduraci Yasemin Ergul , Ozbek Hanefi
Published: October 2020

The aim of this study was to determine the efficacy of an energy restriction intermittent fasting diet in metabolic biomarkers and weight management among adults with metabolic syndrome. This randomized controlled study was performed with metabolic syndrome patients, aged 18–65 years, at an academic institution in Istanbul, Turkey (n = 70). All participants were randomized to the Intermittent Energy Restriction (IER) intervention group and Continuous Energy Restriction (CER) control group. Biochemical tests including lipid profile, fasting plasma glucose, insulin, glycosylated hemoglobin Type A1c (HbA1c), homeostatic model assessment of insulin resistance (HOMA-IR), blood pressure, and body composition were evaluated at baseline and at the 12th week in diet interviews. Dietary intake was measured with the 24-h dietary recall method and dietary quality was evaluated with the Healthy Eating Index-2010. Changes in body weight (≈7% weight loss) and composition were similar in both groups. Blood pressure, total cholesterol, triglyceride, low-density lipoprotein (LDL), fasting glucose, and insulin at the 12th week decreased in both groups (p < 0.05). No significant differences were observed in metabolic syndrome biomarkers between the IER and CER groups. The energy-restricted intermittent fasting diet did not cause any deficiencies in macronutrient and fiber intake in the subjects. Healthy Eating Index (HEI) index scores were achieved similarly in both groups, and subjects’ dietary intakes were close to daily reference nutritional intake values. The technique used to achieve energy restriction, whether intermittent or continuous, appears to alleviate the metabolic syndrome biomarkers activated by weight loss.
Studying the Relationship of Intermittent Fasting and β-Amyloid in Animal Model of Alzheimer’s Disease: A Scoping Review
Authors: Nasaruddin Muhammad Luqman , Syed Abd Halim Syarifah Aisyah , Kamaruzzaman Mohd Amir
Published: October 2020

We examined the evidence for intermittent fasting (IF) as a preventative tool to influence β-amyloid in animal models of Alzheimer’s disease (AD). A Scopus, Ovid, PubMed, and Web of Science (WoS), search yielded 29 results using the keywords “amyloid beta”, “intermittent fasting”, “intermittent caloric restriction”, “alternate day fasting”, “modified alternate-day fasting”, “time-restricted feeding”, “Ramadan fast”, “intermittent calori* restriction”, “intermittent restrictive diet”, and “Alzheimer*”. Five research articles addressed directly the effects of intermittent fasting on β-amyloid levels in animal models of AD: alternate day fasting (ADF) and time-restricted feeding (TRF) methods were incorporated in these studies. The study designs were found to be heterogeneous. Variations in the levels of β-amyloid peptides or plaque in either the hippocampus, cortical areas, or both in animals following dietary intervention were observed as compared to the ad libitum group. Non-significant changes were observed in three studies, while two studies interestingly demonstrated amelioration and reduction in β-amyloid levels. Given the conflicting results obtained from this study, significant care has to be taken into consideration before the protocol can be applied as a preventative approach to treat Alzheimer’s disease. Longitudinal research is warranted to fully grasp how dietary habits can help alleviate the disease either through upstream or downstream of AD pathology.
A High Protein Calorie Restriction Diet Alters the Gut Microbiome in Obesity
Authors: Dong Tien S. , Luu Kayti , Lagishetty Venu , Sedighian Farzaneh , Woo Shih-Lung , Dreskin Benjamin W. , Katzka William , Chang Candace , Zhou Yi , Arias-Jayo Nerea , Yang Julianne , Ahdoot Aaron , Li Zhaoping , Pisegna Joseph R. , Jacobs Jonathan P.
Published: October 2020

Background: High protein calorie restriction diets have shown clinical efficacy for obesity, but the mechanisms are not fully known. The intestinal microbiome is a mediator of obesity and preclinical data support an effect of high protein diet (HPD) on the gut microbiome of obesity, but there are few studies in humans. Methods: To address this, we conducted a dietary intervention trial of 80 overweight and obese subjects who were randomized to a calorie-restricted high protein diet (HPD) (30% calorie intake) or calorie-restricted normal protein diet (NPD) (15%) for 8 weeks. Baseline dietary intake patterns were assessed by the Diet History Questionnaire III. Longitudinal fecal sampling was performed at baseline, week 1, week 2, week 4, week 6, and week 8, for a total of 365 samples. Intestinal microbiome composition was assessed by 16S rRNA gene sequencing. Results: At baseline, microbial composition was associated with fiber and protein intake. Subjects on the HPD showed a significant increase in microbial diversity as measured by the Shannon index compared to those on the NPD. The HPD was also associated with significant differences in microbial composition after treatment compared to the NPD. Both diets induced taxonomic shifts compared to baseline, including enrichment of Akkermansia spp. and Bifidobacterium spp. and depletion of Prevotella spp. Conclusion: These findings provide evidence that weight loss diets alter the gut microbiome in obesity and suggest differential effects of HPDs compared to NPDs which may influence the clinical response to HPD.
Cardiotoxicity Associated with Gemcitabine: Literature Review and a Pharmacovigilance Study
Authors: Hilmi Marc , Ederhy Stéphane , Waintraub Xavier , Funck-Brentano Christian , Cohen Ariel , Vozy Aurore , Lebrun-Vignes Bénédicte , Moslehi Javid , Nguyen Lee S. , Salem Joe-Elie
Published: October 2020

Background: Gemcitabine is a nucleoside analog, widely used either alone or in combination, for the treatment of multiple cancers. However, gemcitabine may also be associated with cardiovascular adverse-drug-reactions (CV-ADR). Methods: First, we searched for all cases of cardiotoxicity associated with gemcitabine, published in MEDLINE on 30 May 2019. Then, we used VigiBase, the World Health Organization’s global database of individual case safety reports, to compare CV-ADR reporting associated with gemcitabine against the full database between inception and 1 April 2019. We used the information component (IC), an indicator value for disproportionate Bayesian reporting. A positive lower end of the 95% credibility interval for the IC (IC025) ≥ 0, is deemed significant. Results: In VigiBase, 46,898 reports were associated with gemcitabine on a total of 18,908,940 in the full database. Gemcitabine was associated with higher reporting for myocardial ischemia (MI, n: 119), pericardial diseases (n: 164), supraventricular arrhythmias (SVA, n: 308) and heart failure (HF, n: 484) versus full database with IC025 ranging between 0.40 and 2.81. CV-ADR were associated with cardiovascular death in up to 17% of cases. Conclusion: Treatment with gemcitabine is associated with potentially lethal CV-ADRs, including MI, pericardial diseases, SVA and HF. These events should be considered in patient care and clinical trial design.