bluuebunny/crossref_metadata_2025 huggingface dataset:
Chitosan-Stabilized Selenium Nanoparticles and Metformin Synergistically Rescue Testicular Oxidative Damage and Steroidogenesis-Related Genes Dysregulation in High-Fat Diet/Streptozotocin-Induced Diabetic Rats
Authors: Abd El-Hakim Yasmina M. , Abdel-Rahman Mohamed Amany , Khater Safaa I. , Hamed Arisha Ahmed , Metwally Mohamed M. M. , Nassan Mohamed A. , Hassan Manal Ewaiss
Published: December 2020

Background: this study examined the metformin (MF) and/or chitosan stabilized selenium nanoparticles (CH-SeNPs) efficacy to alleviate the male reproductive function impairment in a high-fat diet feed with low-dose streptozotocin (HFD/STZ) induced type 2 diabetes mellitus (T2DM) diabetic rat model. Methods: control non-diabetic, HFD/STZ diabetic, HFD/STZ+MF, HFD/STZ+CH-SeNPs, and HFD/STZ+MF+CH-SeNPs rat groups were used. After 60 days, semen evaluation, hormonal assay, enzymatic antioxidant, lipid peroxidation, testis histopathology, and the steroidogenesis-related genes mRNA expressions were assessed. Results: in the HFD/STZ diabetic rats, sperm count and motility, male sexual hormones, and testicular antioxidant enzymes were significantly reduced. However, sperm abnormalities and testicular malondialdehyde were significantly incremented. The steroidogenesis-related genes, including steroidogenic acute regulatory protein (StAr), cytochrome11A1 (CYP11A1), cytochrome17A1 (CYP17A1), and hydroxysteroid 17-beta dehydrogenase 3 (HSD17B3), and the mitochondrial biogenesis related genes, including peroxisome proliferator-activated receptor gamma coactivator 1-alpha (PGCα) and sirtuin (SIRT), were significantly downregulated in the HFD/STZ diabetic rats. However, CYP19A1mRNA expression was significantly upregulated. In contrast, MF and/or CH-SeNPs oral dosing significantly rescued the T2DM-induced sperm abnormalities, reduced sperm motility, diminished sexual hormones level, testicular oxidative damage, and steroidogenesis-related genes dysregulation. In the MF and CH-SeNP co-treated group, many of the estimated parameters differ considerably from single MF or CH-SeNPs treated groups. Conclusions: the MF and CH-SeNPs combined treatment could efficiently limit the diabetic complications largely than monotherapeutic approach and they could be considered a hopeful treatment option in the T2DM.
Iterative MLFMA-MADBT Technique for Analysis of Antenna Mounted on Large Platforms
Authors: Pang Mingjie , Wang Han , Lin Hai
Published: December 2020

A hybrid technique combining the multi-level fast multipole algorithm (MLFMA) and the modified adaptive division beam tracing (MADBT) is presented to analyze the radiation patterns of the antennas mounted on large-scale complex platforms. In this technique, the MLFMA is used to characterize the antenna and the transition region that cannot be analyzed accurately by high-frequency asymptotic methods. The MADBT method is used to analyze the contribution of the platforms to the entire radiation pattern by tracing all beams effectively. By applying the beam-based MADBT method instead of the conventional current-based physical optics (PO) method to the platforms, the multi-bounce effects inside the platforms are considered, which enhances the accuracy of the radiation patterns, especially for the complex platforms with corner reflector. An iteration method is proposed to model the interaction between the antennas and the platforms strictly. The proposed iterative MLFMA-MADBT method is mesh-independent and can avoid the matrix-vector production (MVP) of the iterative MLFMA-PO method in each iteration. These characters significantly reduce the memory and time consumption in computation while keeping high accuracy. Numerical results are presented to demonstrate the accuracy and efficiency of the proposed hybrid technique.
A Study on Mechanical Characteristics of Cement Composites Fabricated with Nano-Silica and Carbon Nanotube
Authors: Raza Ali , Bhandari Manan , Kim Hyeong-Ki , Son Hyeong-Min , Huang Baofeng , Nam Il-Woo
Published: December 2020

In this study, cement composites were fabricated with various contents of added nano-silica (NS) and multi-walled carbon nanotubes (MWNTs). The compressive and flexural strengths of the resultant cement composites were examined. To explore the microstructures and MWNT distribution, electrical conductivity tests, and scanning electron microscopy were conducted. In addition, the strength results were analyzed based on thermal analysis and porosity evaluations. The electrical conductivity results indicated that MWNTs were satisfactorily distributed in the cement composites. In the mechanical strength tests, the composite with a 0.6% MWNT and 5% NS content and another with a 0.3% MWNT and 5% NS content yielded enhancements in the compressive and flexural strengths of 17.2% and 52% compared with the control samples, respectively. However, composites containing relatively large amounts of both NS and MWNTs showed degradation in the mechanical strength. The enhancement or degradation of the strength was supported by porosity evaluations and thermal analysis results. In particular, the degradation of the strength due to the incorporation of large amounts of both MWNTs and NS was explained by thermogravimetric analysis, which indicated a limited generation of calcium silicate hydrate (C-S-H) hydration products. The lower generation of C-S-H was likely due to the dense microstructure of MWNT/NS-incorporated cement hindering the reactions between calcium hydroxide and the NS.
Morphological Study of Bacillus thuringiensis Crystals and Spores
Authors: Loutfi Hadi , Fayad Nancy , Pellen Fabrice , Le Jeune Bernard , Chakroun Maissa , Benfarhat Dalel , Lteif Roger , Kallassy Mireille , Le Brun Guy , Abboud Marie
Published: December 2020

In this paper, we report a morphological study of the crystals and spores of different shapes synthesized by seven different strains of Bacillus thuringiensis. Crystals and spores were separated after 48 h of culture on T3 agar medium and imaged under a scanning electron microscope (SEM). Sizes of the crystals and spores were determined using Image J software. The results showed that crystal and spore sizes were normally distributed. In addition, the volumes and aspect ratios of the crystals and spores were calculated. The statistical analysis of the data showed the variability of the size distribution and morphological data of the crystals produced by the analyzed strains. Furthermore, variations in spore size and shape within the same serovar were observed, indicating that, perhaps, there are still some unexplored differences between strains of this serovar, making them less identical than what was believed so far.
Distribution of Growth-Inhibiting Bacteria against the Toxic Dinoflagellate Alexandrium catenella (Group I) in Akkeshi-Ko Estuary and Akkeshi Bay, Hokkaido, Japan
Authors: Onishi Yuka , Tuji Akihiro , Yamaguchi Atsushi , Imai Ichiro
Published: December 2020

The distribution of growth-inhibiting bacteria (GIB) against the toxic dinoflagellate Alexandrium catenella (Group I) was investigated targeting seagrass leaves and surface waters at the seagrass bed of Akkeshi-ko Estuary and surface waters of nearshore and offshore points of Akkeshi Bay, Japan. Weekly samplings were conducted from April to June in 2011. GIBs were detected from surface of leaves of the seagrass Zostera marina in Akkeshi-ko Estuary (7.5 × 105–4.7 × 106 colony-forming units: CFU g−1 wet leaf) and seawater at the stations in Akkeshi Bay (6.7 × 100–1.1 × 103 CFU mL−1). Sequence analyses revealed that the same bacterial strains with the same 16S rRNA sequences were isolated from the surface biofilm of Z. marina and the seawater in the Akkeshi Bay. We therefore strongly suggested that seagrass beds are the source of algicidal and growth-inhibiting bacteria in coastal ecosystems. Cells of A.catenella were not detected from seawaters in Akkeshi-ko Estuary and the coastal point of Akkeshi Bay, but frequently detected at the offshore point of Akkeshi Bay. It is suggested that A.catenella populations were suppressed by abundant GIBs derived from the seagrass bed, leading to the less toxin contamination of bivalves in Akkeshi-ko Estuary.
A Cyanobacteria-Based Biofilm System for Advanced Brewery Wastewater Treatment
Authors: Papadopoulos Konstantinos P. , Economou Christina N. , Tekerlekopoulou Athanasia G. , Vayenas Dimitris V.
Published: December 2020

Algal/cyanobacterial biofilm photobioreactors provide an alternative technology to conventional photosynthetic systems for wastewater treatment based on high biomass production and easy biomass harvesting at low cost. This study introduces a novel cyanobacteria-based biofilm photobioreactor and assesses its performance in post-treatment of brewery wastewater and biomass production. Two different supporting materials (glass/polyurethane) were tested to investigate the effect of surface hydrophobicity on biomass attachment and overall reactor performance. The reactor exhibited high removal efficiency (over 65%) of the wastewater’s pollutants (chemical oxygen demand, nitrate, nitrite, ammonium, orthophosphate, and total Kjeldahl nitrogen), while biomass per reactor surface reached 13.1 and 12.8 g·m−2 corresponding to 406 and 392 mg·L−1 for glass and polyurethane, respectively, after 15 days of cultivation. The hydrophilic glass surface favored initial biomass adhesion, although eventually both materials yielded complete biomass attachment, highlighting that cell-to-cell interactions are the dominant adhesion mechanism in mature biofilms. It was also found that the biofilm accumulated up to 61% of its dry weight in carbohydrates at the end of cultivation, thus making the produced biomass a suitable feedstock for bioethanol production.
Organizational Factors That Drive to BIM Effectiveness: Technological Learning, Collaborative Culture, and Senior Management Support
Authors: Villena-Manzanares Francisco , García-Segura Tatiana , Pellicer Eugenio
Published: December 2020

Senior management support is a key dynamic capacity for design companies in the architecture, engineering, and construction (AEC) industry, given the fact that they must identify changes in the competitive environment, which are increasingly becoming more and more technological. In addition, senior management support is obliged to react in the most efficient and effective way. Currently, the project design teams that have adopted building information modeling (BIM) are subject to constant changes in the technological environment, of which the activity is influenced by the behavior of senior management support. This research focuses on this issue by analyzing the role played by the variables of technological learning, collaborative culture, and support provided by senior management as precedents of BIM technology effectiveness. The data set has been obtained from 92 AEC companies in Spain. Using partial least squares (PLS), this research finds evidence of the previously mentioned relationships and the existence of partial mediation effects generated by technological learning and collaborative culture within the support of senior management in BIM technology effectiveness. In addition, this model achieves an appropriate level of predictive validation to explain BIM technology effectiveness in engineering project designs. The results highlight that senior management support needs to promote a technological learning and collaborative culture to improve the technological capabilities. The contribution and original value of the paper is to provide empirical evidence that the effectiveness of BIM factors in project design teams is influenced by the behavior of top management support.
Preparation of the Orange Flavoured “Boba” Ball in Milk Tea and Its Shelf-Life
Authors: Liu Ying , Cheng Huan , Wu Dan
Published: December 2020

Boba milk tea is very popular around the world. The “boba” balls in milk tea are usually made of tapioca. Reports on calcium alginate ball encapsulation in fruit-flavoured drinks have rarely been seen. The preparation method for this kind ball was studied. The “boba” balls were obtained by membrane formation on the interface through the addition of calcium chloride fluids into a sodium alginate solution. The operation conditions were studied, including drop height, flow velocity, sodium alginate and calcium chloride solution concentration. The diameter, mechanical strength, loading ratio and encapsulation rate of the “boba” balls are discussed. The optimized preparation conditions were as follows: the diameter of adding tube was 8 mm, the drop height was 25 cm, the drop flow rate was 60 mL/min, 1.0% sodium alginate, 1.0% calcium chloride. The prepared “boba” balls were stored at different temperatures. No microorganisms were detected in 90 days, and the sensory quality decreased with storage time. Shelf life was predicted using the Arrhenius equation; when the storage temperature was less than 10 °C, it could be stored for more than 1 year. This preparation technology of “boba” balls has potential for application by milk tea ingredient companies or relevant beverage manufacturing factories.
Effect of Iron Loading on the Catalytic Activity of Fe/N-Doped Reduced Graphene Oxide Catalysts via Irradiation
Authors: Rahman Kazi Rumanna , Kok Kuan Ying , Wong Wai Yin , Yang Hsiharng , Lim Kean Long
Published: December 2020

The aim of this study is to produce noble-metal-free oxygen reduction reaction (ORR) catalyst via irradiation. Gamma ray irradiation reduction has been utilized to produce N-doped reduced graphene oxide (rGO)-supported iron (Fe)-based catalysts, whose weight percent (wt.%) of Fe loading varies from 10% to 20%. In this study, the physicochemical properties of Fe/N-rGO with various loadings of Fe (10 wt.%, 15 wt.% and 20 wt.%) were explored through X-ray diffraction (XRD), field emission scanning electron microscopy-energy dispersive spectroscopy (FESEM-EDS), Raman spectroscopy and Fourier transform infrared spectroscopy (FTIR). XRD showed that a broad-peak nanocrystallite Fe2O3 phase formed. Raman spectroscopy revealed that Fe insertion increased the disordered GO structure. Fourier transform infrared (FTIR) demonstrated that N was functionalized into rGO. FESEM-EDX presented that Fe nanoparticles existed on the wrinkled rGO surface but their amount was low. Linear sweep voltammetry (LSV) was performed with a rotating disk electrode in 0.1 M KOH at a scanning rate of 20 mVs−1 and revolution rates of 400, 900 and 1600 rpm and the corresponding electron transfer numbers were investigated with a Koutecky–Levich model. This model indicated that the number of electron transfers of 20% Fe/N-rGO was above 2 and its performance toward ORR was higher than those of 10% Fe/N-rGO and 15% Fe/N-rGO.
Thermoelastic Investigation of Carbon-Fiber-Reinforced Composites Using a Drop-Weight Impact Test
Authors: Andleeb Zahra , Malik Sohail , Abbas Khawaja Hassan , Samuelsen Nordli Anders , Antonsen Ståle , Hussain Ghulam , Moatamedi Mojtaba
Published: December 2020

Composite materials are becoming more popular in technological applications due to the significant weight savings and strength offered by these materials compared to metallic materials. In many of these practical situations, the structures suffer from drop-impact loads. Materials and structures significantly change their behavior when submitted to impact loading conditions compared to quasi-static loading. The present work is devoted to investigating the thermal process in carbon-fiber-reinforced polymers (CFRP) subjected to a drop test. A novel drop-weight impact test experiment is performed to evaluate parameters specific to 3D composite materials. A strain gauge rosette and infrared thermography are employed to record the kinematic and thermal fields on the composites’ surfaces. This technique is nondestructive and offers an extensive full-field investigation of a material’s response. The combination of strain and infrared thermography data allows a comprehensive analysis of thermoelastic effects in CFRP when subjected to impacts. The experimental results are validated using numerical analysis by developing a MATLAB® code to analyze whether the coupled heat and wave equation phenomenon exists in a two-dimensional polar coordinate system by discretizing through a forward-time central-space (FTCS) finite-difference method (FDM). The results show the coupling has no significant impact as the waves generated due to impact disappears in 0.015 s. In contrast, heat diffusion happens for over a one-second period. This study demonstrates that the heat equation alone governs the CFRP heat flow process, and the thermoelastic effect is negligible for the specific drop-weight impact load.
Stability Assessment of Current Controller with Harmonic Compensator for LCL-Filtered Grid-Connected Inverter under Distorted Weak Grid
Authors: Yoon Seung-Jin , Tran Thuy Vi , Kim Kyeong-Hwa
Published: December 2020

An assessment of the stability and performance of current controllers with harmonic compensators is presented for an inductive-capacitive-inductive (LCL)-filtered grid-connected inverter under distorted weak grid conditions. By using two typical current control schemes which are the direct current controller with the capacitor current-based active damping and integral-resonant state feedback current controller, the closed-loop system stability and current control performance are investigated in the presence of both uncertain grid impedance and distorted grid. Even though the controller stability has been investigated under weak grid in several studies, the stability assessment of the entire current control scheme, including the harmonic resonant controllers, still needs a further comprehensive investigation. The system stability is analyzed by obtaining the movement of the closed-loop poles in the discrete-time domain when the grid impedance varies. To fully study the impact of distorted weak grid condition on the LCL filters, three LCL filter parameter sets giving the resonance frequency in different frequency bands are chosen for the purpose of evaluating the system robustness and grid-injected current quality. In order to support the presented theoretical analyses, comprehensive simulation and experimental results based on 32-bit DSP TMS320F28335 to control 2 kVA grid-connected inverter are presented in terms of grid current quality and control stability in the environment of both uncertain grid impedance and distorted grid.
Culture Media and Sampling Collection Method for Aspergillus spp. Assessment: Tackling the Gap between Recommendations and the Scientific Evidence
Authors: Viegas Carla , Dias Marta , Carolino Elisabete , Sabino Raquel
Published: December 2020

Culturing is still the most widely used method for determining fungal growth. Thus, is important to identify the most suitable culture media to assess Aspergillus spp. The aim of this study was to analyze data obtained from previous studies, aiming at identifying the most suitable culture media (malt extract agar (MEA) or dichloran-glycerol agar (DG18) to assess Aspergillus spp. isolation and growth. This study was conducted by using environmental samples (n = 1153). Most of the active sampling methods (air samples) were impacted directly onto both culture media. As for passive sampling methods, fungi were extracted from environmental matrices inoculated onto both media. Overall, total Aspergillus counts were higher in MEA (n = 617, 53.5%) than in DG18 (n = 536, 46.5%). Regarding Aspergillus sections, significant associations were detected with the media (χ2 (7) = 241.118, p < 0.001), the sampling approach (p < 0.001, 95% CI = (0.3 × 10−4), and the indoor environment (p < 0.001, 95% CI = (0.3 × 10−4)). As such, sampling approach and the culture media should be accurately selected when dealing with Aspergillus spp. exposure assessment.
The Bone Buttress Theory: The Effect of the Mechanical Loading of Bone on the Osseointegration of Dental Implants
Authors: Chavarri-Prado David , Brizuela-Velasco Aritza , Álvarez-Arenal Ángel , Dieguez-Pereira Markel , Pérez-Pevida Esteban , Viteri-Agustín Iratxe , Estrada-Martínez Alejandro
Published: December 2020

Objectives: To determine the effect of mechanical loading of bone on the stability and histomorphometric variables of the osseointegration of dental implants using an experimental test in an animal model. Materials and Methods: A total of 4 human implants were placed in both tibiae of 10 New Zealand rabbits (n = 40). A 6-week osseointegration was considered, and the rabbits were randomly assigned to two groups: Group A (Test group) included 5 rabbits that ran on a treadmill for 20 min daily during the osseointegration period; Group B (Controls) included the other 5 that were housed conventionally. The monitored variables were related to the primary and secondary stability of the dental implants (implant stability quotient—ISQ), vertical bone growth, bone to implant contact (BIC), area of regenerated bone and the percentage of immature matrix. Results: The results of the study show a greater vertical bone growth (Group A 1.26 ± 0.48 mm, Group B 0.32 ± 0.47 mm, p < 0.001), higher ISQ values (Group A 11.25 ± 6.10 ISQ, 15.73%; Group B 5.80 ± 5.97 ISQ, 7.99%, p = 0.006) and a higher BIC (Group A 19.37%, Group B 23.60%, p = 0.0058) for implants in the test group, with statistically significant differences. A higher percentage of immature bone matrix was observed for implants in the control group (20.68 ± 9.53) than those in the test group (15.38 ± 8.84) (p = 0.108). A larger area of regenerated bone was also observed for the test implants (Group A 280.50 ± 125.40 mm2, Group B 228.00 ± 141.40 mm2), but it was not statistically significant (p = 0.121). Conclusions: The mechanical loading of bone improves the stability and the histomorphometric variables of the osseointegration of dental implants.
Role of TGF-Beta and Smad7 in Gut Inflammation, Fibrosis and Cancer
Authors: Stolfi Carmine , Troncone Edoardo , Marafini Irene , Monteleone Giovanni
Published: December 2020

The human gastrointestinal tract contains the largest population of immune cells in the body and this is a reflection of the fact that it is continuously exposed to a myriad of dietary and bacterial antigens. Although these cells produce a variety of inflammatory cytokines that could potentially promote tissue damage, in normal conditions the mucosal immune response is tightly controlled by counter-regulatory factors, which help induce and maintain gut homeostasis and tolerance. One such factor is transforming growth factor (TGF)-β1, a cytokine produced by multiple lineages of leukocytes, stromal cells and epithelial cells, and virtually targets all the gut mucosal cell types. Indeed, studies in animals and humans have shown that defects in TGF-β1 production and/or signaling can lead to the development of immune-inflammatory pathologies, fibrosis and cancer in the gut. Here, we review and discuss the available evidence about the role of TGF-β1 and Smad7, an inhibitor of TGF-β1 activity, in gut inflammation, fibrosis and cancer with particular regard to the contribution of these two molecules in the pathogenesis of inflammatory bowel diseases and colon cancer.
The Molecular Mechanisms Associated with Aerobic Exercise-Induced Cardiac Regeneration
Authors: Bo Bing , Zhou Yang , Zheng Qingyun , Wang Guandong , Zhou Ke , Wei Jianshe
Published: December 2020

The leading cause of heart failure is cardiomyopathy and damage to the cardiomyocytes. Adult mammalian cardiomyocytes have the ability to regenerate, but this cannot wholly compensate for myocardial cell loss after myocardial injury. Studies have shown that exercise has a regulatory role in the activation and promotion of regeneration of healthy and injured adult cardiomyocytes. However, current research on the effects of aerobic exercise in myocardial regeneration is not comprehensive. This review discusses the relationships between aerobic exercise and the regeneration of cardiomyocytes with respect to complex molecular and cellular mechanisms, paracrine factors, transcriptional factors, signaling pathways, and microRNAs that induce cardiac regeneration. The topics discussed herein provide a knowledge base for physical activity-induced cardiomyocyte regeneration, in which exercise enhances overall heart function and improves the efficacy of cardiac rehabilitation.
Low Molecular Weight Hyaluronic Acid Effect on Dental Pulp Stem Cells In Vitro
Authors: Schmidt Jan , Pilbauerova Nela , Soukup Tomas , Suchankova-Kleplova Tereza , Suchanek Jakub
Published: December 2020

Hyaluronic acid (HA) and dental pulp stem cells (DPSCs) are attractive research topics, and their combined use in the field of tissue engineering seems to be very promising. HA is a natural extracellular biopolymer found in various tissues, including dental pulp, and due to its biocompatibility and biodegradability, it is also a suitable scaffold material. However, low molecular weight (LMW) fragments, produced by enzymatic cleavage of HA, have different bioactive properties to high molecular weight (HMW) HA. Thus, the impact of HA must be assessed separately for each molecular weight fraction. In this study, we present the effect of three LMW-HA fragments (800, 1600, and 15,000 Da) on DPSCs in vitro. Discrete biological parameters such as DPSC viability, morphology, and cell surface marker expression were determined. Following treatment with LMW-HA, DPSCs initially presented with an acute reduction in proliferation (p < 0.0016) and soon recovered in subsequent passages. They displayed significant size reduction (p = 0.0078, p = 0.0019, p = 0.0098) while maintaining high expression of DPSC markers (CD29, CD44, CD73, CD90). However, in contrast to controls, a significant phenotypic shift (p < 0.05; CD29, CD34, CD90, CD106, CD117, CD146, CD166) of surface markers was observed. These findings provide a basis for further detailed investigations and present a strong argument for the importance of HA scaffold degradation kinetics analysis.
Phellodendron amurense Extract Protects Human Keratinocytes from PM2.5-Induced Inflammation via PAR-2 Signaling
Authors: Choi Jiyoung , Moon Mi Yeon , Han Gi Yeon , Chang Moon Sik , Yang Dongki , Cha Joonseok
Published: December 2020

Dietary supplement and personal care products aiming to provide protection from air pollution have been of great interest for decades. Epidemiology demonstrated that PM10 and PM2.5 particulate matter (PM) are an actual threat to public health worldwide, but the detailed processes of how these particles attack the cells are not fully understood. Here, we report that the measurement of intracellular calcium concentration ([Ca2+]i) using human respiratory or skin cells can illustrate pollutant challenges by triggering Ca2+ influx in these cells. This signal was generated by proteinase-activated receptor-2 (PAR-2), confirmed by competition analyses, and Phellodendron amurense bark extract (PAE), a traditional medicine, was able to control the response and expression of PAR-2. Increase in proinflammatory cytokines and decrease in cell adhesion components could suggest a severe damage status by air pollutants and protection by PAE. Finally, we identified 4-O-feruloylquinic acid (FQA), an active compound of PAE, showing the same effects on Ca2+ influx and PAR-2 regulation. The results presented here should help understand the underlying mechanism of PM insults and the beneficial effect of standardized PAE as dietary supplement or cosmetical ingredient.
Interstitial Pneumonia with Autoimmune Features: Why Rheumatologist-Pulmonologist Collaboration Is Essential
Authors: Sebastiani Marco , Faverio Paola , Manfredi Andreina , Cassone Giulia , Vacchi Caterina , Stainer Anna , Pozzi Maria Rosa , Salvarani Carlo , Pesci Alberto , Luppi Fabrizio
Published: December 2020

In 2015 the European Respiratory Society (ERS) and the American Thoracic Society (ATS) “Task Force on Undifferentiated Forms of Connective Tissue Disease-associated Interstitial Lung Disease” proposed classification criteria for a new research category defined as “Interstitial Pneumonia with Autoimmune Features” (IPAF), to uniformly define patients with interstitial lung disease (ILD) and features of autoimmunity, without a definite connective tissue disease. These classification criteria were based on a variable combination of features obtained from three domains: a clinical domain consisting of extra-thoracic features, a serologic domain with specific autoantibodies, and a morphologic domain with imaging patterns, histopathological findings, or multicompartment involvement. Features suggesting a systemic vasculitis were excluded. Since publication of ERS/ATS IPAF research criteria, various retrospective studies have been published focusing on prevalence; clinical, morphological, and serological features; and prognosis of these patients showing a broad heterogeneity in the results. Recently, two prospective, cohort studies were performed, confirming the existence of some peculiarities for this clinical entity and the possible progression of IPAF to a defined connective tissue disease (CTD) in about 15% of cases. Moreover, a non-specific interstitial pneumonia pattern, an anti-nuclear antibody positivity, and a Raynaud phenomenon were the most common findings. In comparison with idiopathic pulmonary fibrosis (IPF), IPAF patients showed a better performance in pulmonary function tests and less necessity of oxygen delivery. However, at this stage of our knowledge, we believe that further prospective studies, possibly derived from multicenter cohorts and through randomized control trials, to further validate the proposed classification criteria are needed.
Endothelial Dysfunction in Diabetes Is Aggravated by Glycated Lipoproteins; Novel Molecular Therapies
Authors: Toma Laura , Stancu Camelia Sorina , Sima Anca Volumnia
Published: December 2020

Diabetes and its vascular complications affect an increasing number of people. This disease of epidemic proportion nowadays involves abnormalities of large and small blood vessels, all commencing with alterations of the endothelial cell (EC) functions. Cardiovascular diseases are a major cause of death and disability among diabetic patients. In diabetes, EC dysfunction (ECD) is induced by the pathological increase of glucose and by the appearance of advanced glycation end products (AGE) attached to the plasma proteins, including lipoproteins. AGE proteins interact with their specific receptors on EC plasma membrane promoting activation of signaling pathways, resulting in decreased nitric oxide bioavailability, increased intracellular oxidative and inflammatory stress, causing dysfunction and finally apoptosis of EC. Irreversibly glycated lipoproteins (AGE-Lp) were proven to have an important role in accelerating atherosclerosis in diabetes. The aim of the present review is to present up-to-date information connecting hyperglycemia, ECD and two classes of glycated Lp, glycated low-density lipoproteins and glycated high-density lipoproteins, which contribute to the aggravation of diabetes complications. We will highlight the role of dyslipidemia, oxidative and inflammatory stress and epigenetic risk factors, along with the specific mechanisms connecting them, as well as the new promising therapies to alleviate ECD in diabetes.
Biosensors for the Multiplex Detection of Inflammatory Disease Biomarkers
Authors: Mobasheri Ali
Published: December 2020

A biosensor is an analytical device used for the real-time detection and measurement of a chemical or biochemical substance [...]
Insulin Resistance in Skeletal Muscle of Chronic Stroke
Authors: Ryan Alice S. , Hafer-Macko Charlene , Ortmeyer Heidi K.
Published: December 2020

A stroke can lead to reduced mobility affecting skeletal muscle mass and fatty infiltration which could lead to systemic insulin resistance, but this has not been examined and the mechanisms are currently unknown. The objective was to compare the effects of in vivo insulin on skeletal muscle glycogen synthase (GS) activity in paretic (P) and nonparetic (NP) skeletal muscle in chronic stroke, and to compare to nonstroke controls. Participants were mild to moderately disabled adults with chronic stroke (n = 30, 60 ± 8 years) and sedentary controls (n = 35, 62 ± 8 years). Insulin sensitivity (M) and bilateral GS activity were determined after an overnight fast and during a hyperinsulinemic-euglycemic clamp. Stroke subjects had lower aerobic capacity than controls, but M was not significantly different. Insulin-stimulated activities of GS (independent, total, fractional), as well as absolute differences (insulin minus basal) and the percent change (insulin minus basal, relative to basal) in GS activities, were all significantly lower in P versus NP muscle. Basal GS fractional activity was 3-fold higher, and the increase in GS fractional activity during the clamp was 2-fold higher in control versus P and NP muscle. Visceral fat and intermuscular fat were associated with lower M. The effect of in vivo insulin to increase GS fractional activity was associated with M in control and P muscle. A reduction in insulin action on GS in paretic muscle likely contributes to skeletal muscle-specific insulin resistance in chronic stroke.
MTHFR Gene Polymorphisms and Cardiovascular Risk Factors, Clinical-Imagistic Features and Outcome in Cerebral Venous Sinus Thrombosis
Authors: Gogu Anca Elena , Jianu Dragos Catalin , Dumitrascu Victor , Ples Horia , Stroe Alina Zorina , Docu Axelerad Daniel , Docu Axelerad Any
Published: December 2020

Cerebral venous sinus thrombosis (CVST) as a severe neurological emergency, is represented by variable conditions in its clinic presentation, onset, risk factors, neuroimagistic features and outcome. The genetic polymorphism of the methylenetetrahydrofolate reductase (MTHFR) gene C677T and A1298C was associated with CVST. We aimed to characterize the prevalence of MTHFR gene polymorphisms associated with cardiovascular risk factors in the group of patients with CVST. Also, we studied additional causes associated with CVST including local infections, general infections, obstetric causes (pregnancy, puerperium) and head injury. This is a retrospective study including 114 patients which referred to our hospital between February 2012–February 2020. The protocol included demographic (age, sex), clinical, neuroimagistic features, paraclinic (genetic polymorphism of MTHFR, factor V G1691A—Leiden, prothrombin G20210A, PAI-1 675 4G/5G; Homocysteine level, the lipid profile, blood glucose and Glycohemoglobin HbA1c, high- sensitive C- reactive protein- hsCRP) data, as well as treatment and outcome. The mean age was 37.55 years with a female predominance (65.79%). In the first group of patients with inherited thrombophilia (60 cases; 52.63%) we found genetic mutation includes MTHFR C677T (38.59%) and A1298C (14.03%), factor V G1691A- Leiden (15.78%), prothrombin G20210A (2.63%), PAI-1 675 4G/5G (42.98%), and hyperhomocysteinemia (35.08%). At the second group with other etiology of CVST, except thrombophilia, we included 54 patients (47.36%). The most common sites of thrombosis were the superior sagittal sinus (52.63%). Headache was the most common symptom (91.22%) and seizures were the main clinical presentation (54.38%). The MTHFR polymorphism was significantly correlated with higher total cholesterol (TC) (p = 0.023), low- density lipoprotein cholesterol (LDL) (p = 0.008), homocysteine level (tHcy) (p < 0.001). Inside the first group with MTHFR polymorphism we have found a significant difference between the levels of homocysteine at the patients with MTHFR C677T versus MTHFR A1298C polymorphism (p < 0.001). The high-sensitive C-reactive protein (hsCRP) was increased in both groups of patients, but the level was much higher in the second group (p = 0.046). Mortality rate was of 2.63%. Demographic, clinical and neuroimagistic presentation of CVST in our study was similar with other studies on the matter, with a high frequency of thrombophilia causes. MTHFR gene polymorphisms (C677T and A1298C) are increased in prevalence in CVST. PAI-1 675 4G/5G gene mutation seems to be involved in CVST etiology. Plasma C-reactive protein level and hyperhomocysteinemia should be considered as a prognostic factor in CVST.
Human Papillomavirus in Sinonasal Squamous Cell Carcinoma: A Systematic Review and Meta-Analysis
Authors: Chang Sing Pang Kim J. W. , Mur Taha , Collins Louise , Rao Sowmya R. , Faden Daniel L.
Published: December 2020

Human papillomavirus (HPV) drives tumorigenesis in a subset of oropharyngeal squamous cell carcinomas (OPSCC) and is increasing in prevalence across the world. Mounting evidence suggests HPV is also involved in a subset of sinonasal squamous cell carcinomas (SNSCC), yet small sample sizes and variability of HPV detection techniques in existing literature hinder definitive conclusions. A systematic review was performed by searching literature through March 29th 2020 using PubMed, Embase, and Web of Science Core Collection databases. Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines were followed by two authors independently. A meta-analysis was performed using the random-effects model. Sixty studies (n = 1449) were eligible for statistical analysis estimating an overall HPV prevalence of 25.5% (95% CI 20.7–31.0). When stratified by HPV detection method, prevalence with multiple substrate testing (20.5%, 95% CI 14.5–28.2) was lower than with single substrate testing (31.7%, 95% CI 23.6–41.1), highest in high-exposure anatomic subsites (nasal cavity and ethmoids) (37.6%, 95% CI 26.5–50.2) vs. low-exposure (15.1%, 95% CI 7.3–28.6) and highest in high HPV+ OPSCC prevalence geographic regions (North America) (30.9%, 95% CI 21.9–41.5) vs. low (Africa) (13.1, 95% CI 6.5–24.5)). While small sample sizes and variability in data cloud firm conclusions, here, we provide a new reference point prevalence for HPV in SNSCC along with orthogonal data supporting a causative role for virally driven tumorigenesis, including that HPV is more commonly found in sinonasal subsites with increased exposure to refluxed oropharyngeal secretions and in geographic regions where HPV+ OPSCC is more prevalent.
Gene Expression Signatures of a Preclinical Mouse Model during Colorectal Cancer Progression under Low-Dose Metronomic Chemotherapy
Authors: Ho-Xuan Hung , Lehmann Gerhard , Glazar Petar , Gypas Foivos , Eichner Norbert , Heizler Kevin , Schlitt Hans J. , Zavolan Mihaela , Rajewsky Nikolaus , Meister Gunter , Hackl Christina
Published: December 2020

Understanding the molecular signatures of colorectal cancer progression under chemotherapeutic treatment will be crucial for the success of future therapy improvements. Here, we used a xenograft-based mouse model to investigate, how whole transcriptome signatures change during metastatic colorectal cancer progression and how such signatures are affected by LDM chemotherapy using RNA sequencing. We characterized mRNAs as well as non-coding RNAs such as microRNAs, long non-coding RNAs and circular RNAs in colorectal-cancer bearing mice with or without LDM chemotherapy. Furthermore, we found that circZNF609 functions as oncogene, since over-expression studies lead to an increased tumor growth while specific knock down results in smaller tumors. Our data represent novel insights into the relevance of non-coding and circRNAs in colorectal cancer and provide a comprehensive resource of gene expression changes in primary tumors and metastases. In addition, we present candidate genes that could be important modulators for successful LDM chemotherapy.
Prognostic Clinical and Biologic Features for Overall Survival after Relapse in Childhood Medulloblastoma
Authors: Huybrechts Sophie , Le Teuff Gwénaël , Tauziède-Espariat Arnault , Rossoni Caroline , Chivet Anaïs , Indersie Émilie , Varlet Pascale , Puget Stéphanie , Abbas Rachid , Ayrault Olivier , Guerrini-Rousseau Léa , Grill Jacques , Valteau-Couanet Dominique , Dufour Christelle
Published: December 2020

Given the very poor prognosis for children with recurrent medulloblastoma, we aimed to identify prognostic factors for survival post-relapse in children with childhood medulloblastoma. We retrospectively collected clinico-biological data at diagnosis and main clinical characteristics at relapse of children newly diagnosed with a medulloblastoma between 2007 and 2017 at Gustave Roussy and Necker Hospital. At a median follow-up of 6.6 years (range, 0.4–12.3 years), relapse occurred in 48 out 155 patients (31%). The median time from diagnosis to relapse was 14.3 months (range, 1.2–87.2 months). Relapse was local in 9, metastatic in 22 and combined (local and metastatic) in 17 patients. Second-line treatment consisted of chemotherapy in 31 cases, radiotherapy in 9, SHH-inhibitor in four and no treatment in the remaining four. The 1-year overall survival rate post-relapse was 44.8% (CI 95%, 31.5% to 59.0%). While molecular subgrouping at diagnosis was significantly associated with survival post-relapse, the use of radiotherapy at relapse and time to first relapse (>12 months) might also have a potential impact on post-relapse survival.
Interpretable Machine Learning Model for Locoregional Relapse Prediction in Oropharyngeal Cancers
Authors: Giraud Paul , Giraud Philippe , Nicolas Eliot , Boisselier Pierre , Alfonsi Marc , Rives Michel , Bardet Etienne , Calugaru Valentin , Noel Georges , Chajon Enrique , Pommier Pascal , Morelle Magali , Perrier Lionel , Liem Xavier , Burgun Anita , Bibault Jean Emmanuel
Published: December 2020

Background: There is no evidence to support surgery or radiotherapy as the best treatment for resectable oropharyngeal cancers with a negative HPV status. Predictive algorithms may help to decide which strategy to choose, but they will only be accepted by caregivers and European authorities if they are interpretable. As a proof of concept, we developed a predictive and interpretable algorithm to predict locoregional relapse at 18 months for oropharyngeal cancers as a first step towards that goal. Methods: The model was based on clinical and Pyradiomics features extracted from the dosimetric CT scan. Intraclass correlation was used to filter out features dependant on delineation. Correlated redundant features were also removed. An XGBoost model was cross-validated and optimised on the HN1 cohort (79 patients), and performances were assessed on the ART ORL cohort (45 patients). The Shapley Values were used to provide an overall and local explanation of the model. Results: On the ART ORL cohort, the model trained on HN1 yielded a precision—or predictive positive value—of 0.92, a recall of 0.42, an area under the curve of the receiver operating characteristic of 0.68 and an accuracy of 0.64. The most contributory features were shape Voxel Volume, grey level size zone matrix Small Area Emphasis (glszmSAE), gldm Dependence Non Uniformity Normalized (gldmDNUN), Sex and Age. Conclusions: We developed an interpretable and generalizable model that could yield a good precision—positive predictive value—for relapse at 18 months on a different test cohort.
Microvascular Density, Endothelial Area, and Ki-67 Proliferative Index Correlate Each Other in Cat Post-Injection Fibrosarcoma
Authors: Patruno Rosa , Passantino Giuseppe , Laface Carmelo , Tinelli Antonella , Zito Alfredo , Ruggieri Roberta , Luposella Francesco , Gadaleta Pietro , Laforgia Mariarita , Lacitignola Luca , Ammendola Michele , Ranieri Girolamo , Zizzo Nicola
Published: December 2020

Soft tissue sarcomas are a large group of different tumor types both in humans and in animals. Among them, fibrosarcoma is the most frequent malignant mesenchymal tumoral form in cats, representing up to 28% of all cat skin tumors, while human fibrosarcoma, fortunately, only represents 5% of all sarcomas and 0.025% of the world-wide burden of tumors. This low incidence in humans leads to consideration of this group of tumoral diseases as rare, so therapeutic options are few due to the difficulty of starting clinical trials. In this context, the identification of research models for fibrosarcomas could be of great interest to deepen knowledge in this field and recognize new or possible biological pathways involved in tumor progression and metastasis. Angiogenesis is considered a fundamental scattering cause of tumor aggressiveness and progression in all forms of cancer, but only a few research parameters were developed and reported to express them quantitatively and qualitatively. The role in angiogenesis of microenvironmental stromal cells, such as fibroblasts, lymphocytes, mast cells, and macrophages, was largely demonstrated since this topic was first approached, while quantification of new vessels and their blood capacity in tumoral area is a relatively recent approach that could be well developed thanks to expertise in immunohistochemistry and image analysis. In this paper, a crossing study evaluating microvascular density (MVD), endothelial area (EA), and Ki-67 proliferative index was reported for a series of formalin-fixed and paraffin-embedded tissue samples from 99 cat patients, affected by cat post-injection fibrosarcoma, by using a till ×400 magnification light microscopy. We aim to demonstrate that cat pets may be considered a useful animal model for better studying the correspondent human diseases and we report, for the first time to our knowledge, experimental data in terms of correlation among MVD, EA, and Ki-67 strictly involved in aggressiveness and tumoral progression.
The Measurement of Strength in Children: Is the Peak Value Truly Maximal?
Authors: Ozaki Hayao , Abe Takashi , Dankel Scott J. , Loenneke Jeremy P. , Natsume Toshiharu , Deng Pengyu , Naito Hisashi
Published: December 2020

It is unclear whether the measurement of maximum muscle strength in younger children can be performed accurately due to factors such as motivation and maturity (i.e., the ability to receive instruction). If there is a large change in a ratio between muscular strength and size from the youngest to the oldest, then this might provide some indication that the youngest may not have been able to voluntarily activate their muscles for reasons mentioned previously. The purpose of this study was to observe the ratio between handgrip strength (HGS) and forearm muscle thickness (MT) across differing ages in younger children. A total of 1133 preschool children (559 boys and 574 girls) between the ages of 4.5 and 6.5 years had MT and HGS measurements and calculated the ratio of HGS/MT (kg/cm). Linear regression was used to assess the impact of age and sex on the dependent variables of MT, HGS, and the HGS/MT ratio. The HGS/MT ratio increases moderately from age 4.5 to 6.5 in both boys and girls. However, the difference in this ratio was small between the age ranges in this sample. Our results indicate children as young as 4.5 may be accurately measured with the handgrip strength test.
Head and Neck Squamous Cell Carcinoma: Epigenetic Landscape
Authors: Romanowska Kamila , Sobecka Agnieszka , Rawłuszko-Wieczorek Agnieszka A. , Suchorska Wiktoria M. , Golusiński Wojciech
Published: December 2020

Head and neck squamous carcinoma (HNSCC) constitutes the sixth most prevalent cancer worldwide. The molecular pathogenesis of HNSCC includes disorders in cell cycle, intercellular signaling, proliferation, squamous cell differentiation and apoptosis. In addition to the genetic mutations, changes in HNSCC are also characterized by the accumulation of epigenetic alterations such as DNA methylation, histone modifications, non-coding RNA activity and RNA methylation. In fact, some of them may promote cancer formation and progression by controlling the gene expression machinery, hence, they could be used as biomarkers in the clinical surveillance of HNSCC or as targets for therapeutic strategies. In this review, we focus on the current knowledge regarding epigenetic modifications observed in HNSCC and its predictive value for cancer development.