bluuebunny/crossref_metadata_2025 huggingface dataset:
Epigenetic Consequences of in Utero Exposure to Rosuvastatin: Alteration of Histone Methylation Patterns in Newborn Rat Brains
Authors: Dulka Karolina , Szabo Melinda , Lajkó Noémi , Belecz István , Hoyk Zsófia , Gulya Karoly
Published: March 2021

Rosuvastatin (RST) is primarily used to treat high cholesterol levels. As it has potentially harmful but not well-documented effects on embryos, RST is contraindicated during pregnancy. To demonstrate whether RST could induce molecular epigenetic events in the brains of newborn rats, pregnant mothers were treated daily with oral RST from the 11th day of pregnancy for 10 days (or until delivery). On postnatal day 1, the brains of the control and RST-treated rats were removed for Western blot or immunohistochemical analyses. Several antibodies that recognize different methylation sites for H2A, H2B, H3, and H4 histones were quantified. Analyses of cell-type-specific markers in the newborn brains demonstrated that prenatal RST administration did not affect the composition and cell type ratios as compared to the controls. Prenatal RST administration did, however, induce a general, nonsignificant increase in H2AK118me1, H2BK5me1, H3, H3K9me3, H3K27me3, H3K36me2, H4, H4K20me2, and H4K20me3 levels, compared to the controls. Moreover, significant changes were detected in the number of H3K4me1 and H3K4me3 sites (134.3% ± 19.2% and 127.8% ± 8.5% of the controls, respectively), which are generally recognized as transcriptional activators. Fluorescent/confocal immunohistochemistry for cell-type-specific markers and histone methylation marks on tissue sections indicated that most of the increase at these sites belonged to neuronal cell nuclei. Thus, prenatal RST treatment induces epigenetic changes that could affect neuronal differentiation and development.
HIF-1α and Pro-Inflammatory Signaling Improves the Immunomodulatory Activity of MSC-Derived Extracellular Vesicles
Authors: Gómez-Ferrer Marta , Villanueva-Badenas Estela , Sánchez-Sánchez Rafael , Sánchez-López Christian M. , Baquero Maria Carmen , Sepúlveda Pilar , Dorronsoro Akaitz
Published: March 2021

Despite the strong evidence for the immunomodulatory activity of mesenchymal stromal cells (MSCs), clinical trials have so far failed to clearly show benefit, likely reflecting methodological shortcomings and lack of standardization. MSC-mediated tissue repair is commonly believed to occur in a paracrine manner, and it has been stated that extracellular vesicles (EVs) secreted by MSCs (EVMSC) are able to recapitulate the immunosuppressive properties of parental cells. As a next step, clinical trials to corroborate preclinical studies should be performed. However, effective dose in large mammals, including humans, is quite high and EVs industrial production is hindered by the proliferative senescence that affects MSCs during massive cell expansion. We generated a genetically modified MSC cell line overexpressing hypoxia-inducible factor 1-alpha and telomerase to increase the therapeutic potency of EVMSC and facilitate their large-scale production. We also developed a cytokine-based preconditioning culture medium to prime the immunomodulatory response of secreted EVs (EVMSC-T-HIFc). We tested the efficacy of this system in vitro and in a delayed-type hypersensitivity mouse model. MSC-T with an HIF-1α-GFP lentiviral vector (MSC-T-HIF) can be effectively expanded to obtain large amounts of EVs without major changes in cell phenotype and EVs composition. EVMSC-T-HIFc suppressed the proliferation of activated T-cells more effectively than did EVs from unmodified MSC in vitro, and significantly blunted the ear-swelling response in vivo by inhibiting cell infiltration and improving tissue integrity. We have developed a long-lived EV source that secretes high quantities of immunosuppressive EVs, facilitating a more standard and cost-effective therapeutic product.
Gastric Cancer: Advances in Carcinogenesis Research and New Therapeutic Strategies
Authors: Seeneevassen Lornella , Bessède Emilie , Mégraud Francis , Lehours Philippe , Dubus Pierre , Varon Christine
Published: March 2021

Gastric cancer’s bad incidence, prognosis, cellular and molecular heterogeneity amongst others make this disease a major health issue worldwide. Understanding this affliction is a priority for proper patients’ management and for the development of efficient therapeutical strategies. This review gives an overview of major scientific advances, made during the past 5-years, to improve the comprehension of gastric adenocarcinoma. A focus was made on the different actors of gastric carcinogenesis, including, Helicobacter pylori cancer stem cells, tumour microenvironment and microbiota. New and recent potential biomarkers were assessed as well as emerging therapeutical strategies involving cancer stem cells targeting as well as immunotherapy. Finally, recent experimental models to study this highly complex disease were discussed, highlighting the importance of gastric cancer understanding in the hard-fought struggle against cancer relapse, metastasis and bad prognosis.
Diabetes and Cardiovascular Risk in Renal Transplant Patients
Authors: Rysz Jacek , Franczyk Beata , Radek Maciej , Ciałkowska-Rysz Aleksandra , Gluba-Brzózka Anna
Published: March 2021

End-stage kidney disease (ESKD) is a main public health problem, the prevalence of which is continuously increasing worldwide. Due to adverse effects of renal replacement therapies, kidney transplantation seems to be the optimal form of therapy with significantly improved survival, quality of life and diminished overall costs compared with dialysis. However, post-transplant patients frequently suffer from post-transplant diabetes mellitus (PTDM) which an important risk factor for cardiovascular and cardiovascular-related deaths after transplantation. The management of post-transplant diabetes resembles that of diabetes in the general population as it is based on strict glycemic control as well as screening and treatment of common complications. Lifestyle interventions accompanied by the tailoring of immunosuppressive regimen may be of key importance to mitigate PTDM-associated complications in kidney transplant patients. More transplant-specific approach can include the exchange of tacrolimus with an alternative immunosuppressant (cyclosporine or mammalian target of rapamycin (mTOR) inhibitor), the decrease or cessation of corticosteroid therapy and caution in the prescribing of diuretics since they are independently connected with post-transplant diabetes. Early identification of high-risk patients for cardiovascular diseases enables timely introduction of appropriate therapeutic strategy and results in higher survival rates for patients with a transplanted kidney.
Effect of Quercetin on ABCC6 Transporter: Implication in HepG2 Migration
Authors: Abruzzese Vittorio , Matera Ilenia , Martinelli Fabio , Carmosino Monica , Koshal Prashant , Milella Luigi , Bisaccia Faustino , Ostuni Angela
Published: March 2021

Quercetin is a member of the flavonoid group of compounds, which is abundantly present in various dietary sources. It has excellent antioxidant properties and anti-inflammatory activity and is very effective as an anti-cancer agent against various types of tumors, both in vivo and in vitro. Quercetin has been also reported to modulate the activity of some members of the multidrug-resistance transporters family, such as P-gp, ABCC1, ABCC2, and ABCG2, and the activity of ecto-5′-nucleotidase (NT5E/CD73), a key regulator in some tumor processes such as invasion, migration, and metastasis. In this study, we investigated the effect of Quercetin on ABCC6 expression in HepG2 cells. ABCC6 is a member of the superfamily of ATP-binding cassette (ABC) transporters, poorly involved in drug resistance, whose mutations cause pseudoxanthoma elasticum, an inherited disease characterized by ectopic calcification of soft connective tissues. Recently, it has been reported that ABCC6 contributes to cytoskeleton rearrangements and HepG2 cell motility through purinergic signaling. Gene and protein expression were evaluated by quantitative Reverse-Transcription PCR (RT-qPCR) and western blot, respectively. Actin cytoskeleton dynamics was evaluated by laser confocal microscopy using fluorophore-conjugated phalloidin. Cell motility was analyzed by an in vitro wound-healing migration assay. We propose that ABCC6 expression may be controlled by the AKT pathway as part of an adaptative response to oxidative stress, which can be mitigated by the use of Quercetin-like flavonoids.
Astrocyte Ca2+ Waves and Subsequent Non-Synchronized Ca2+ Oscillations Coincide with Arteriole Diameter Changes in Response to Spreading Depolarization
Authors: Tóth Réka , Farkas Attila E. , Krizbai István A. , Makra Péter , Bari Ferenc , Farkas Eszter , Menyhárt Ákos
Published: March 2021

Spreading depolarization (SD) is a wave of mass depolarization that causes profound perfusion changes in acute cerebrovascular diseases. Although the astrocyte response is secondary to the neuronal depolarization with SD, it remains to be explored how glial activity is altered after the passage of SD. Here, we describe post-SD high frequency astrocyte Ca2+ oscillations in the mouse somatosensory cortex. The intracellular Ca2+ changes of SR101 labeled astrocytes and the SD-related arteriole diameter variations were simultaneously visualized by multiphoton microscopy in anesthetized mice. Post-SD astrocyte Ca2+ oscillations were identified as Ca2+ events non-synchronized among astrocytes in the field of view. Ca2+ oscillations occurred minutes after the Ca2+ wave of SD. Furthermore, fewer astrocytes were involved in Ca2+ oscillations at a given time, compared to Ca2+ waves, engaging all astrocytes in the field of view simultaneously. Finally, our data confirm that astrocyte Ca2+ waves coincide with arteriolar constriction, while post-SD Ca2+ oscillations occur with the peak of the SD-related vasodilation. This is the first in vivo study to present the post-SD astrocyte Ca2+ oscillations. Our results provide novel insight into the spatio-temporal correlation between glial reactivity and cerebral arteriole diameter changes behind the SD wavefront.
Construction of a Full-Length cDNA Over-Expressing Library to Identify Valuable Genes from Populus tomentosa
Authors: Kong Lingfei , Li Zeyu , Song Qin , Li Xiaohong , Luo Keming
Published: March 2021

Poplar wood is the main source of renewable biomass energy worldwide, and is also considered to be a model system for studying woody plants. The Full-length cDNA Over-eXpressing (FOX) gene hunting system is an effective method for generating gain-of-function mutants. Large numbers of novel genes have successfully been identified from many herbaceous plants according to the phenotype of gain-of-function mutants under normal or abiotic stress conditions using this system. However, the system has not been used for functional gene identification with high-throughput mutant screening in woody plants. In this study, we constructed a FOX library from the Chinese white poplar, Populus tomentosa. The poplar cDNA library was constructed into the plant expression vector pEarleyGate101 and further transformed into Arabidopsis thaliana (thale cress). We collected 1749 T1 transgenic plants identified by PCR. Of these, 593 single PCR bands from different transgenic lines were randomly selected for sequencing, and 402 diverse sequences of poplar genes were isolated. Most of these genes were involved in photosynthesis, environmental adaptation, and ribosome biogenesis based on Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway annotation. We characterized in detail two mutant lines carrying PtoCPCa or PtoWRKY13 cDNA insertions. Phenotypic characterization showed that overexpression of these genes in A. thaliana affected trichome development or secondary cell wall (SCW) deposition, respectively. Together, the Populus-FOX-Arabidopsis library generated in our experiments will be helpful for efficient discovery of novel genes in poplar.
Small Molecule Inhibitors of White Spot Syndrome Virus: Promise in Shrimp Seedling Culture
Authors: Liu Lei , Shan Li-Peng , Zhou Yan , Chen Jiong
Published: March 2021

Rapid production of prawn (Litopenaeus vannamei) under artificial pressure can result in a series of obvious challenges and is vulnerable to serious losses related to aquatic environmental issues and the unrestrained outbreak of white spot syndrome (WSS). However, to date, there are no therapeutic strategies to contain the spread of the virus. Here, we synthesized 27 coumarin derivatives and evaluated their anti-white spot syndrome virus (WSSV) activity in L. vannamei larvae. We demonstrated that electron-withdrawing and electron-giving substituent groups play an important role in reducing toxicity and WSSV replication, respectively. Two coumarin C2 (2-amino-5-oxo-4-(p-tolyl)-4H,5H-pyrano[3,2-c]chromene-3-carbonitrile) and C7 (2-amino-4-(4-chlorophenyl)-5-oxo-4H,5H-pyrano[3,2-c]chromene-3-carbonitrile) were regarded as the most promising anti-WSSV compounds with maximum antiviral response <5% and median effective concentration <10 mg/L. The mortality of WSSV-infected larvae decreased by more than 60% after exposure to C2 and C7. With continuous immersion of C2 and C7 exchange, the mortality further decreased to 40% at 120 h. Additionally, C2 and C7 are the relatively stable in aquacultural water, making these agents suitable for use in inhibiting WSSV horizontal transmission in static aquaculture systems. These results showed the marked advantages of using C2 and C7 in the shrimp industry, and suggest that they hold potential for the treatment and prevention of WSSV infection in shrimp seedling culture.
Mycobacterium tuberculosis Load in Host Cells and the Antibacterial Activity of Alveolar Macrophages Are Linked and Differentially Regulated in Various Lung Lesions of Patients with Pulmonary Tuberculosis
Authors: Ufimtseva Elena G. , Eremeeva Natalya I. , Umpeleva Tatiana V. , Vakhrusheva Diana V. , Skornyakov Sergey N.
Published: March 2021

Tuberculosis (TB) is a disease caused by Mycobacterium tuberculosis (Mtb) infection with the formation of a broad range of abnormal lung lesions within a single patient. Although host–pathogen interactions determine disease outcome, they are poorly understood within individual lesions at different stages of maturation. We compared Mtb load in a tuberculoma wall and the lung tissue distant from tuberculomas in TB patients. These data were combined with an analysis of activation and bactericidal statuses of alveolar macrophages and other cell subtypes examined both in ex vivo culture and on the histological sections obtained from the same lung lesions. The expression of pattern recognition receptors CD14, CD11b, and TLR-2, transcription factors HIF-1α, HIF-2α, and NF-κB p50 and p65, enzymes iNOS and COX-2, reactive oxygen species (ROS) biosynthesis, and lipid production were detected for various lung lesions, with individual Mtb loads in them. The walls of tuberculomas with insufficient inflammation and excessive fibrosis were identified as being the main niche for Mtb survival (single or as colonies) in non-foamy alveolar macrophages among various lung lesions examined. The identification of factors engaged in the control of Mtb infection and tissue pathology in local lung microenvironments, where host–pathogen relationships take place, is critical for the development of new therapeutic strategies.
BIM-Based Description of Intelligent Transportation Systems for Roads
Authors: Mirboland Mahsa , Smarsly Kay
Published: March 2021

Intelligent transportation systems (ITS) provide safer, greener, and more convenient mobility, while reducing the impact on the environment. In recent years, simulation platforms have been employed to study ITS applications, mostly focusing on traffic-related simulations. Despite several research studies on ITS applications and simulation platforms, formal semantic descriptions of intelligent transportation systems have not been addressed yet. In this paper, a semantic model describing intelligent transportation systems for roads is proposed. The semantic model is devised to provide a basis for designing ITS simulation platforms. Building upon the semantic model, an extension to an open building information modeling (BIM) standard, i.e., the Industry Foundation Classes (IFC) schema, is presented. The IFC schema extension is verified and validated using a BIM-based simulation scenario of ITS for roads. It is shown that the proposed IFC-compliant description of ITS for roads provides a formal basis for generating BIM-based simulations and hence facilitates ITS infrastructure modeling in BIM projects. It is concluded that the present work represents a cornerstone for designing BIM-based ITS simulation platforms. In future endeavors, potential standardization and formalization efforts may be discussed.
Mechanosensitive Pathways in Heart Development: Findings from Chick Embryo Studies
Authors: Alser Maha , Shurbaji Samar , Yalcin Huseyin C.
Published: March 2021

The heart is the first organ that starts to function in a developing embryo. It continues to undergo dramatic morphological changes while pumping blood to the rest of the body. Genetic regulation of heart development is partly governed by hemodynamics. Chick embryo is a major animal model that has been used extensively in cardiogenesis research. To reveal mechanosensitive pathways, a variety of surgical interferences and chemical treatments can be applied to the chick embryo to manipulate the blood flow. Such manipulations alter expressions of mechanosensitive genes which may anticipate induction of morphological changes in the developing heart. This paper aims to present different approaches for generating clinically relevant disturbed hemodynamics conditions using this embryonic chick model and to summarize identified mechanosensitive genes using the model, providing insights into embryonic origins of congenital heart defects.
The Novel Technique of Uniportal Endoscopic Interlaminar Contralateral Approach for Coexisting L5-S1 Lateral Recess, Foraminal, and Extraforaminal Stenosis and Its Clinical Outcomes
Authors: Kim Ji Yeon , Kim Hyeun Sung , Jeon Jun Bok , Lee Jun Hyung , Park Jun Hwan , Jang Il-Tae
Published: March 2021

Background: Multifocal intra-and-extraspinal lumbar stenotic lesions could be decompressed with one endoscopic surgical approach, which has the advantages of functional structure preservation, technical efficacy, and safety. Methods: A retrospective study was performed on 48 patients who underwent uniportal endoscopic contralateral approach due to coexisting lateral recess, foraminal, and extraforaminal stenosis at the L5-S1 level. Foraminal stenosis grade and postoperative dysesthesia (POD) were analyzed. Visual analog scale (VAS) pain scores, modified Oswestry Disability Index (ODI) scores, and MacNab criteria for evaluating pain disability and response were analyzed. Results: The foraminal stenosis grade of the treated spinal levels was grade 1 (n = 16, 33%), grade 2 (n = 20, 42%), and grade 3 (n = 12, 25%). The rate of occurrence of POD grade 2 and above, which may be related to intraoperative dorsal root ganglion (DRG) retraction injury, was revealed to be 4.2% (two with grade 2, none with grade 3). The patients showed favorable clinical outcomes. Conclusions: Uniportal endoscopic interlaminar contralateral approach is an effective procedure to resolve combined stenosis (lateral recess, foraminal, and extraforaminal region) with one surgical approach at the L5-S1 level. It may be a minimal DRG retracting and facet joint preserving procedure in foraminal and extraforaminal decompression.
PD-(L)1 Inhibitors as Monotherapy for the First-Line Treatment of Non-Small-Cell Lung Cancer Patients with High PD-L1 Expression: A Network Meta-Analysis
Authors: Majem Margarita , Cobo Manuel , Isla Dolores , Marquez-Medina Diego , Rodriguez-Abreu Delvys , Casal-Rubio Joaquín , Moran-Bueno Teresa , Bernabé-Caro Reyes , Pérez-Parente Diego , Ruiz-Gracia Pedro , Arroyo Marta Marina , Paz-Ares Luis
Published: March 2021

Programmed cell death-ligand 1 (PD-L1) has emerged as a potential biomarker for selection of patients more likely to respond to immunotherapy and as a prognostic factor in non-small cell lung cancer (NSCLC). In this network meta-analysis, we aimed to evaluate the efficacy of first-line anti-PD-(L)1 monotherapy in advanced NSCLC patients with high PD-L1 expression (≥50%) compared to platinum-based chemotherapy. We also evaluated efficacy outcomes according to tumor mutational burden (TMB). To that end, we conducted a systematic review. Six clinical trials with 2111 patients were included. In head-to-head comparisons, immunotherapy showed a significant improvement in progression-free survival (PFS: HRpooled = 0.69, 95% CI: 0.52–0.90, p = 0.007), overall survival (OS: HRpooled = 0.69, 95% CI: 0.61–0.78; p < 0.001) and overall response rate (ORR) (Risk ratio (RR)pooled = 1.354, 95% CI: 1.04–1.762, p = 0.024). In the assessment of relative efficacy for PFS through indirect comparisons, pembrolizumab (results from KEYNOTE-024) ranked highest followed by cemiplimab and atezolizumab, with statistical significance determined for some of the drugs. In terms of OS, cemiplimab ranked highest followed by atezolizumab and pembrolizumab, although non-significant OS was determined for these drugs. In conclusion, PD-(L)1 inhibitor monotherapy improves efficacy outcomes in the first line setting of advanced NSCLC patients with high PD-L1 expression. Evaluations with longer follow up are still needed to determine the superiority of any specific drug.
Checkpoint Inhibitors as High-Grade Gliomas Treatment: State of the Art and Future Perspectives
Authors: Persico Pasquale , Lorenzi Elena , Dipasquale Angelo , Pessina Federico , Navarria Pierina , Politi Letterio S. , Santoro Armando , Simonelli Matteo
Published: March 2021

Glioblastoma (GBM) is the most common and aggressive malignant brain tumor in adults. Despite significant efforts, no therapies have demonstrated valuable survival benefit beyond the current standard of care. Immune checkpoint inhibitors (ICI) have revolutionized the treatment landscape and improved patient survival in many advanced malignancies. Unfortunately, these clinical successes have not been replicated in the neuro-oncology field so far. This review summarizes the status of ICI investigation in high-grade gliomas, critically presenting the available data from preclinical models and clinical trials. Moreover, we explore new approaches to increase ICI efficacy, with a particular focus on combinatorial strategies, and the potential biomarkers to identify patients most likely to benefit from immune checkpoint blockade.
Hole-Expansion: Sensitivity of Failure Prediction on Plastic Anisotropy Modeling
Authors: Ha Jinjin , Korkolis Yannis P.
Published: March 2021

The influence of yield function parameters on hole-expansion (HE) predictions are investigated for an anisotropic AA6022-T4 aluminum sheet. The HE experiment is performed in a fully-instrumented double-action hydraulic press with a flat-headed punch. Full strain fields are measured by a stereo-type digital image correlation (DIC) system. The stress state gradually changes from uniaxial to plane-strain tension to biaxial tension in the radial direction. Besides HE, the plastic anisotropy of AA6022-T4 is characterized by uniaxial tension and plane-strain tension experiments. Uniaxial tension is considered as the most important, since it is the stress state along the hoop direction in the hole. For the finite element (FE) simulation, the Yld2000-2d non-quadratic anisotropic yield function is used with two different parameter sets, calibrated by: (1) uniaxial tension only (termed Calib1) and, (2) both uniaxial and plane-strain tension (Calib2). The strain field predictions show a good agreement with the experiments only for Calib2, which takes into account plane-strain as well uniaxial tension. This indicates the importance of biaxial modes, and in particular plane-strain tension, for the adopted yield function to produce accurate HE simulations.
Smooth Signals and Syntactic Change
Authors: Wallenberg Joel C. , Bailes Rachael , Cuskley Christine , Ingason Anton Karl
Published: March 2021

A large body of recent work argues that considerations of information density predict various phenomena in linguistic planning and production. However, the usefulness of an information theoretic account for explaining diachronic phenomena has remained under-explored. Here, we test the idea that speakers prefer informationally uniform utterances on diachronic data from historical English and Icelandic. Our results show that: (i) the information density approach allows us to predict that Subject and Object type will affect the frequencies of OV and VO in specific ways, creating a complex Constant Rate Effect, (ii) the bias towards information uniformity explains this CRE and may help to explain others, and (iii) communities of speakers are constant in their average target level of information uniformity over long periods of historical time. This finding is consistent with an understanding of this bias which places it deep in the human language faculty and the human faculty for communication.
Student Speech and Social Media: The Supreme Court Finally Enters the Fray
Authors: Russo Charles J.
Published: March 2021

Tinker v. Des Moines Independent Community School District was a watershed moment involving the First Amendment free speech rights of students in American public schools. In Tinker, the Supreme Court affirmed that absent a reasonable forecast of material and substantial disruption, educators could not discipline students who wore black arm bands to school protesting American military action in Viet Nam. Not surprisingly, litigation continues on the boundaries of student speech, coupled with the extent to which educators can limit expression on the internet, especially social media. As the Justices finally entered the fray over cyber speech, this three-part article begins by reviewing Tinker and other Supreme Court precedent on student expressive activity plus illustrative lower court cases before examining Levy v. Mahanoy Area School District. In Levy, the Court will consider whether educators could discipline a cheerleader, a student engaged in an extracurricular activity, who violated team rules by posting inappropriate off-campus messages on Snapchat. The article then offers policy suggestions for lawyers and educators when working with speech codes applicable to student use of the internet and social media by pupils involved in extracurricular activities.
Immunoreactivity of Muscarinic Acetylcholine M2 and Serotonin 5-HT2B Receptors, Norepinephrine Transporter and Kir Channels in a Model of Epilepsy
Authors: Akyuz Enes , Doganyigit Zuleyha , Paudel Yam Nath , Koklu Betul , Kaymak Emin , Villa Chiara , Arulsamy Alina , Shaikh Mohd. Farooq , Devinsky Orrin
Published: March 2021

Epilepsy is characterized by an imbalance in neurotransmitter activity; an increased excitatory to an inhibitory activity. Acetylcholine (ACh), serotonin, and norepinephrine (NE) may modulate neural activity via several mechanisms, mainly through its receptors/transporter activity and alterations in the extracellular potassium (K+) concentration via K+ ion channels. Seizures may disrupt the regulation of inwardly rectifying K+ (Kir) channels and alter the receptor/transporter activity. However, there are limited data present on the immunoreactivity pattern of these neurotransmitter receptors/transporters and K+ channels in chronic models of epilepsy, which therefore was the aim of this study. Changes in the immunoreactivity of epileptogenesis-related neurotransmitter receptors/transporters (M2, 5-HT2B, and NE transporter) as well as Kir channels (Kir3.1 and Kir6.2) were determined in the cortex, hippocampus and medulla of adult Wistar rats by utilizing a Pentylenetetrazol (PTZ)-kindling chronic epilepsy model. Increased immunoreactivity of the NE transporter, M2, and 5-HT2B receptors was witnessed in the cortex and medulla. While the immunoreactivity of the 5-HT2B receptor was found increased in the cortex and medulla, it was decreased in the hippocampus, with no changes observed in the M2 receptor in this region. Kir3.1 and Kir6.2 staining showed increase immunoreactivity in the cerebral cortex, but channel contrasting findings in the hippocampus and medulla. Our results suggest that seizure kindling may result in significant changes in the neurotransmitter system which may contribute or propagate to future epileptogenesis, brain damage and potentially towards sudden unexpected death in epilepsy (SUDEP). Further studies on the pathogenic role of these changes in neurotransmitter receptors/transporters and K+ channel immunoreactivity may identify newer possible targets to treat seizures or prevent epilepsy-related comorbidities.
Reproductive Potential and Outcomes in Patients with Hidradenitis Suppurativa: Clinical Profile and Therapeutic Implications
Authors: Montero-Vilchez Trinidad , Salvador-Rodriguez Luis , Rodriguez-Tejero Andrea , Sanchez-Diaz Manuel , Arias-Santiago Salvador , Molina-Leyva Alejandro
Published: March 2021

There are scarce data available regarding the impact of hidradenitis suppurativa (HS) on fertility, course and outcome of pregnancy and risk associated with treatments. The aims of this study are (1) to describe the clinical profile of HS women of childbearing age with and without accomplished reproductive desires and (2) to describe the prescribed treatments based on the fulfillment of reproductive intentions. We conducted a prospective observational study that included 104 HS women of childbearing age, 50.96% (53/104) with unfulfilled reproductive desires. These women were younger (29.08 vs. 42.06 years, p < 0.001), less frequently married and higher educated than women with fulfilled reproductive desires. Their age of disease onset was lower, but disease duration was shorter, in concordance with a lower International Hidradenitis Suppurativa Severity Score System (IHS4) and lower number of draining tunnels. Combined oral contraceptives were more frequently prescribed in women with unfulfilled reproductive desires (30.19% vs. 9.80%, p = 0.013) while biologics were less used in this group (3.77% vs. 13.73%, p = 0.08). In conclusion, a higher educational level and an earlier disease onset, with potential implications in finding a partner, may make the fulfillment of reproductive desires difficult for patients with HS. This study could help clinicians to achieve a better understanding of the specific characteristics of HS during childbearing age and consider reproductive desires when making treatment decisions.
Changing in Larch Sapwood Extractives Due to Distinct Ionizing Radiation Sources
Authors: Schnabel Thomas , Barbu Marius Cătălin , Tudor Eugenia Mariana , Petutschnigg Alexander
Published: March 2021

Wood extractives have an influence on different material properties. This study deals with the changes in wood extractives of larch sapwood due to two different low doses of energy irradiations. Electron beam irradiation (EBI) and γ-ray irradiation treatments were done by using two industrial processes. After the different modifications the extractions were performed with an accelerated solvent extractor (ASE) using hexane and acetone/water. The qualitative and quantitative chemical differences of irradiated larch sapwood samples were analysed using gas chromatography–mass spectrometry (GC-MS) and Fourier-transform infrared spectroscopy (FT-IR) vibrational spectroscopy methods. The yields of the quantitative extractions decreased due to the two different irradiation processes. While the compounds extracted with nonpolar solvent from wood were reduced, the number of compounds with polar functionalities increased based on the oxidation process. Quantitatively, resin acids and polyphenols were highly affected when exposed to the two irradiation sources, leading to significant changes (up, down) in their relative amount. Furthermore, two new substances were found in the extracts of larch sapwood samples after EBI or γ-ray treatments. New insight into the different effects of larch sapwood and wood extractives by EBI and γ-ray was gained in this study.
Surface Integrity of Dimethacrylate Composite Resins with Low Shrinkage Comonomers
Authors: He Jingwei , Garoushi Sufyan , Säilynoja Eija , Vallittu Pekka , Lassila Lippo
Published: March 2021

The goal of current research was to investigate the influence of adding low shrinkage “Phene” like comonomers hexaethylene glycol bis(carbamate-isoproply-α-methylstyrene) (HE-Phene) and triethylene glycol bis(carbamate-isoproply-α-methylstyrene) (TE-Phene) on the surface and color characteristics of composite resin. A range of weight fractions (0, 10, 20, 30, 40 wt.%) of HE/TE-Phene monomers were mixed with bisphenol A glycidyl methacrylate (GMA)/triethylene glycol dimethacrylate (TEGDMA) monomer. Experimental composite resins were made by mixing 71 wt.% of silica fillers to 29 wt.% of the resin matrix. A Vickers indenter and glossmeter were used for testing surface hardness (SH) and gloss (SG) at 60°. A chewing-simulator was used to evaluate the surface wear after 15,000 cycles. Color change (∆E) and translucency parameter (TP) were measured using a spectrophotometer. Data showed that HE/TE-Phene monomer had no negative impact (p > 0.05) on surface gloss, wear, color change and translucency of experimental composite resins. Surface hardness was in a reducing direction with the increas in HE/TE-Phene weight fraction (p < 0.05). The study results suggested that incorporating HE/TE-Phene monomers up to 30 wt.% with Bis-GMA/TEGDMA resin did not negatively influence the surface integrity of composite resins except for SH.
Spicy Bitumen: Curcumin Effects on the Rheological and Adhesion Properties of Asphalt
Authors: Abe Abraham A. , Oliviero Rossi Cesare , Caputo Paolino , De Santo Maria Penelope , Godbert Nicolas , Aiello Iolinda
Published: March 2021

Over the years, the need for the synthesis of biodegradable materials has facilitated the drift of the asphalt industry towards eco-sustainable and cost-effective production of road pavements. The principal additives in the asphalt industry to improve the performance of road pavements and increase its lifespan are majorly rheological modifiers, adhesion promoters and anti-oxidant agents. Rheological modifiers increase physico-chemical properties such as transition temperature of asphalt binder (bitumen), adhesion promoters increase the affinity between binder and stone aggregates while anti-oxidant agents reduce the effects of oxidation caused by exposure to air, water and other natural elements during the production of asphalt pavements. In this study, we tested the effectiveness of a food grade bio-additive on these three aforementioned properties. We also sought to hypothesize the mechanisms by which the additive confers these desired features on bitumen. We present this study to evaluate the effects of turmeric, a food-based additive, on bitumen. The study was conducted through dynamic shear rheology (DSR), atomic force microscopy, scanning electron microscopy (SEM) and boiling test analysis.
Cutting Forces and Tool Wear Investigation during Turning of Sintered Nickel-Cobalt Alloy with CBN Tools
Authors: Zębala Wojciech , Struzikiewicz Grzegorz , Rumian Ksenia
Published: March 2021

This article describes issues related to the machining of parts made of sintered nickel-cobalt alloy. Longitudinal turning with a CBN (cubic boron nitride) tool was analyzed. The results of experiments showed the influence of cutting parameters in the field of finishing machining on the values of cutting forces and specific cutting force, taking into account the wear of the cutting edge. Measurements and analysis of the topography and roughness parameters of the machined surface, as well as the cutting tool wear, were presented. The microscopic examination showed that the average grain size of the sintered nickel-cobalt alloy was 3.22 ± 0.1 (μm). The presence of the hardening state variability of the material during machining, as well as the value of the cutting force fluctuation as a function of the tool wear VB, were stated. The specific cutting force values increased to a small degree for the tool wear in the range of VB = 0–0.2 mm, and reached similar values in the range kc = 5500–7500 N/mm2. The specific cutting force values increased significantly for wear VB > 0.2 mm and were characterized by a large variability. The occurring phenomena were analyzed and several explanations were proposed. A recommendation was developed for the machining of parts made of sintered nickel-cobalt alloy. The Taguchi method was used in the experiment methodology.
Characterization and Programming Algorithm of Phase Change Memory Cells for Analog In-Memory Computing
Authors: Antolini Alessio , Franchi Scarselli Eleonora , Gnudi Antonio , Carissimi Marcella , Pasotti Marco , Romele Paolo , Canegallo Roberto
Published: March 2021

In this paper, a thorough characterization of phase-change memory (PCM) cells was carried out, aimed at evaluating and optimizing their performance as enabling devices for analog in-memory computing (AIMC) applications. Exploiting the features of programming pulses, we discuss strategies to reduce undesired phenomena that afflict PCM cells and are particularly harmful in analog computations, such as low-frequency noise, time drift, and cell-to-cell variability of the conductance. The test vehicle is an embedded PCM (ePCM) provided by STMicroelectronics and designed in 90-nm smart power BCD technology with a Ge-rich Ge-Sb-Te (GST) alloy for automotive applications. On the basis of the results of the characterization of a large number of cells, we propose an iterative algorithm to allow multi-level cell conductance programming, and its performances for AIMC applications are discussed. Results for a group of 512 cells programmed with four different conductance levels are presented, showing an initial conductance spread under 6%, relative current noise less than 9% in most cases, and a relative conductance drift of 15% in the worst case after 14 h from the application of the programming sequence.
Stress Intensity Factor Assessment for the Reinforcement of Cracked Steel Plates Using Prestressed or Non-Prestressed Adhesively Bonded CFRP
Authors: Lepretre Emilie , Chataigner Sylvain , Dieng Lamine , Gaillet Laurent
Published: March 2021

The use of adhesively bonded carbon fiber reinforced polymer (CFRP) materials to reinforce cracked steel elements has gained widespread acceptance in order to extend the lifespan of metallic structures. This allows an important reduction of the stress intensity factor (SIF) at the crack tip and thus a significant increase of the fatigue life. This paper deals with the assessment of the SIF for repaired cracked steel plates, using semi-empirical analysis and finite element analysis. Metallic plates with only one crack originating from a center hole were investigated. Virtual crack closure technique (VCCT) was used to define and evaluate the stress intensity factor at crack tip. The obtained modeling results are compared with experimental investigations led by the authors for different reinforcement configurations including symmetrical and non-symmetrical reinforcement, normal modulus and ultra-high-modulus CFRP plates, and pre-stressed CFRP plates. Results show that finite element model (FEM) analysis can obviously simulate the fatigue performance of the CFRP bonded steel plates with different reinforcement configurations. Moreover, a parametric analysis of the influence of the pre-stressing level was also conducted. The results show that an increase of the pre-stressing level results in an increase of the fatigue life of the element.
Physical Characterization of Bismuth Oxide Nanoparticle Based Ceramic Composite for Future Biomedical Application
Authors: Jagdale Pravin , Serino Gianpaolo , Oza Goldie , Audenino Alberto Luigi , Bignardi Cristina , Tagliaferro Alberto , Alvarez-Gayosso Carlos
Published: March 2021

Employment and the effect of eco-friendly bismuth oxide nanoparticles (BiONPs) in bio-cement were studied. The standard method was adopted to prepare BiONPs-composite. Water was adopted for dispersing BiONPs in the composite. A representative batch (2 wt. % of BiONPs) was prepared without water to study the impact of water on composite properties. For each batch, 10 samples were prepared and tested. TGA (thermogravimetric analysis) performed on composite showed 0.8 wt. % losses in samples prepared without water whereas, maximum 2 wt. % weight losses observed in the water-based composite. Presence of BiONPs resulted in a decrease in depth of curing. Three-point bending flexural strength decreased for increasing BiONPs content. Comparative study between 2 wt. % samples with and without water showed 10.40 (±0.91) MPa and 28.45 (±2.50) MPa flexural strength values, respectively, indicating a significant (p < 0.05) increase of the mechanical properties at the macroscale. Nanoindentation revealed that 2 wt. % without water composites showed significant (p < 0.05) highest nanoindentation modulus 26.4 (±1.28) GPa and hardness 0.46 (±0.013) GPa. Usage of water as dispersion media was found to be deleterious for the overall characteristics of the composite but, at the same time, the BiONPs acted as a very promising filler that can be used in this class of composites.
Impact of TiO2 Nanostructures on Dye-Sensitized Solar Cells Performance
Authors: Gnida Paweł , Jarka Paweł , Chulkin Pavel , Drygała Aleksandra , Libera Marcin , Tański Tomasz , Schab-Balcerzak Ewa
Published: March 2021

The effect of TiO2 nanostructures such as nanoparticles, nanowires, nanotubes on photoanode properties, and dye-sensitized solar cells photovoltaic parameters were studied. The series of dye-sensitized solar cells based on two dyes, that is, commercially N719 and synthesized 3,7′-bis(2-cyano-1-acrylic acid)-10-ethyl-phenothiazine were tested. Additionally, the devices containing a mixture of this sensitizer and chenodeoxycholic acid as co-adsorbent were fabricated. The amount of adsorbed dye molecules to TiO2 was evaluated. The prepared photoanodes with different TiO2 nanostructures were investigated using UV-Vis spectroscopy, optical, atomic force, and scanning electron microscopes. Photovoltaic response of constructed devices was examined based on current-voltage characteristics and electrochemical impedance spectroscopy measurements. It was found that the highest UV-Vis absorption exhibited the photoanode with nanotubes addition. This indicates the highest number of sensitizer molecules anchored to the titanium dioxide photoanode, which was subsequently confirmed by dye-loading tests. The highest power conversion efficiency was (6.97%) for solar cell containing nanotubes and a mixture of the dyes with a co-adsorbent.
Characterization of High-Temperature Superconductor Bulks for Electrical Machine Application
Authors: Douine Bruno , Berger Kevin , Ivanov Nickolay
Published: March 2021

High-temperature superconducting (HTS) bulks can be used in electrical applications. Experimental characterization of large-size HTS bulks is a tricky issue. The relevant parameters for their application were directly measured in this study. This paper has three main aims. Firstly, features of YBaCuO bulks are presented. Secondly, an electrical motor application is developed using magnetic field shielding and trapping. Thirdly, the HTS bulks are characterized. Several classical methods were used, which are mainly magnetic methods only available for small samples. The complete penetration magnetic field and the critical current density were found to be the main parameters relevant for applications. An innovative entire HTS bulk characterization method is presented. This characterization method is useful for end users and engineers to better implement HTS bulks.
Molecular Characterization of the Von Willebrand Factor Type D Domain of Vitellogenin from Takifugu flavidus
Authors: Qiao Kun , Jiang Caiyun , Xu Min , Chen Bei , Qiu Wenhui , Su Yongchang , Hao Hua , Lin Zhiyong , Cai Shuilin , Su Jie , Liu Zhiyu , Huang Wenshu
Published: March 2021

The von Willebrand factor type D (VWD) domain in vitellogenin has recently been found to bind tetrodotoxin. The way in which this protein domain associates with tetrodotoxin and participates in transporting tetrodotoxin in vivo remains unclear. A cDNA fragment of the vitellogenin gene containing the VWD domain from pufferfish (Takifugu flavidus) (TfVWD) was cloned. Using in silico structural and docking analyses of the predicted protein, we determined that key amino acids (namely, Val115, ASP116, Val117, and Lys122) in TfVWD mediate its binding to tetrodotoxin, which was supported by in vitro surface plasmon resonance analysis. Moreover, incubating recombinant rTfVWD together with tetrodotoxin attenuated its toxicity in vivo, further supporting protein–toxin binding and indicating associated toxicity-neutralizing effects. Finally, the expression profiling of TfVWD across different tissues and developmental stages indicated that its distribution patterns mirrored those of tetrodotoxin, suggesting that TfVWD may be involved in tetrodotoxin transport in pufferfish. For the first time, this study reveals the amino acids that mediate the binding of TfVWD to tetrodotoxin and provides a basis for further exploration of the molecular mechanisms underlying the enrichment and transfer of tetrodotoxin in pufferfish.
Validation of Cognitive Rehabilitation as a Balance Rehabilitation Strategy in Patients with Parkinson’s Disease: Study Protocol for a Randomized Controlled Trial
Authors: Arroyo-Ferrer Aida , Sánchez-Cuesta Francisco José , González-Zamorano Yeray , del Castillo María Dolores , Sastre-Barrios Carolina , Ríos-Lago Marcos , Romero Juan Pablo
Published: March 2021

Background: Parkinson’s disease (PD) is the second most common neurodegenerative disorder. This disease is characterized by motor symptoms, such as bradykinesia, tremor, and rigidity. Although balance impairment is characteristic of advanced stages, it can be present with less intensity since the beginning of the disease. Approximately 60% of PD patients fall once a year and 40% recurrently. On the other hand, cognitive symptoms affect up to 20% of patients with PD in early stages and can even precede the onset of motor symptoms. There are cognitive requirements for balance and can be challenged when attention is diverted or reduced, linking a worse balance and a higher probability of falls with a slower cognitive processing speed and attentional problems. Cognitive rehabilitation of attention and processing speed can lead to an improvement in postural stability in patients with Parkinson’s. Methods: We present a parallel and controlled randomized clinical trial (RCT) to assess the impact on balance of a protocol based on cognitive rehabilitation focused on sustained attention through the NeuronUP platform (Neuronup SI, La Rioja, Spain) in patients with PD. For 4 weeks, patients in the experimental group will receive cognitive therapy three days a week while the control group will not receive any therapy. The protocol has been registered at trials.gov NCT04730466. Conclusions: Cognitive therapy efficacy on balance improvement may open the possibility of new rehabilitation strategies for prevention of falls in PD, reducing morbidity, and saving costs to the health care system.
Numerical Modeling of Plasticity-Induced Fatigue Crack Growth Retardation Due to Deflection in the Near-Tip Area
Authors: Toribio Jesús , Matos Juan-Carlos , González Beatriz
Published: March 2021

This article studies the retardation effect in plasticity-induced fatigue crack growth rate for a low-medium strength steel, due to the appearance of microdeflections in the crack path. To this end, the finite element method was used to model the crack with its kinked tip under several stress intensity factor (SIF) ranges. The results allowed a calculation (after a small number of cycles) of the fatigue crack propagation rate for the multiaxial and uniaxial fatigue configurations at the microscopic level. It was observed that the retardation effect rose with an increase in the initial kinked crack tip angle, an increase in the initial projected kinked crack tip length, and with a decrease in the SIF range.