bluuebunny/crossref_metadata_2025 huggingface dataset:
A Genomic Study of Myxomatous Mitral Valve Disease in Cavalier King Charles Spaniels
Authors: Bionda Arianna , Cortellari Matteo , Bagardi Mara , Frattini Stefano , Negro Alessio , Locatelli Chiara , Brambilla Paola Giuseppina , Crepaldi Paola
Published: October 2020

Cavalier King Charles spaniels (CKCSs) show the earliest onset and the highest incidence of myxomatous mitral valve disease (MMVD). Previous studies have suggested a polygenic inheritance of the disease in this breed and revealed an association with regions on canine chromosomes 13 and 14. Following clinical and echocardiographic examinations, 33 not-directly-related CKCSs were selected and classified as cases (n = 16) if MMVD was present before 5 years of age or as controls (n = 17) if no or very mild MMVD was present after 5 years of age. DNA was extracted from whole blood and genotyped with a Canine 230K SNP BeadChip instrument. Cases and controls were compared with three complementary genomic analyses (Wright’s fixation index—FST, cross-population extended haplotype homozygosity—XP-EHH, and runs of homozygosity—ROH) to identify differences in terms of heterozygosity and regions of homozygosity. The top 1% single-nucleotide polymorphisms (SNPs) were selected and mapped, and the genes were thoroughly investigated. Ten consensus genes were found localized on chromosomes 3-11-14-19, partially confirming previous studies. The HEPACAM2, CDK6, and FAH genes, related to the transforming growth factor β (TGF-β) pathway and heart development, also emerged in the ROH analysis. In conclusion, this work expands the knowledge of the genetic basis of MMVD by identifying genes involved in the early onset of MMVD in CKCSs.
Effect of Aging Time on Meat Quality of Longissimus Dorsi from Yunling Cattle: A New Hybrid Beef Cattle
Authors: Fan Yongliang , Han Ziyin , ARBAB Abdelaziz Adam Idriss , Yang Yi , Yang Zhangping
Published: October 2020

The beef aging process is essential for compliance with certain major requisites, such as sensory characteristics for cooking and meat processing. Meat quality analysis of Yunling cattle, a new hybrid beef cattle bred by Chinese researchers, during the aging process, represents a major research gap. To explore Yunling beef initially, indicators associated with meat quality during the aging process of Yunling, Simmental, and Wenshan cattle were measured. In addition, some important economic traits were detected in the three breeds, including growth performance and carcass characteristics. The results showed that the growth performance, carcass traits, pH, and water holding capacity of Yunling and Simmental cattle were basically the same and better, respectively, than those of Wenshan cattle. The proportions of individual fatty acids in Yunling beef were healthier than in the other two breeds. Aging time did not affect the fatty acid profiles of the beef (p > 0.05). The contents of certain fatty acids in the three beef types displayed some differences in terms of days of aging (p < 0.05). The tenderness and meat color were better in the Yunling beef as the aging time increased, indicating that Yunling beef aged for 7 days was more suitable for cooking, exhibiting better sensory characteristics. Thus, a 7-day short-term aging process is very effective in improving the quality of Yunling beef. Our study attempted to fill a gap in the Yunling beef quality analysis during aging, providing further evidence for Yunling beef improvement.
The Epidemiology of African Swine Fever, Its Complexity and the Requirement for Multiple Solution Approaches
Authors: Schulz Katja , Boklund Anette
Published: October 2020

Searching for the term “African swine fever” (ASF) in the title of publications in the Web of Science, PubMed and Scopus during the period of 1955–2020 resulted in an average of 2009 detected articles [...]
Prevalence and Epidemiology of Multidrug-Resistant Pathogens in the Food Chain and the Urban Environment in Northwestern Germany
Authors: Klees Sylvia , Effelsberg Natalie , Stührenberg Birgit , Mellmann Alexander , Schwarz Stefan , Köck Robin
Published: October 2020

The surveillance of antimicrobial resistance among humans and food-producing animals is important to monitor the zoonotic transmission of multidrug-resistant bacteria (MDRB). We assessed the prevalence of four MDRB within the meat production chain, including extended-spectrum β-lactamase (ESBL)-producing, carbapenemase-producing Enterobacterales (CPE) and colistin-resistant Enterobacterales (Col-E), as well as vancomycin-resistant enterococci (VRE). In total, 505 samples from four stages of meat production, i.e., slaughterhouses, meat-processing plants, fresh food products and the urban environment, were collected in northwestern Germany in 2018/2019 and screened for the presence of MDRB using both culture-based and PCR-based techniques. We detected genes encoding for carbapenemases in 9–56% (blaOXA-48, blaKPC, blaNDM, blaVIM) and colistin resistance-encoding mcr genes in 9–26% of the samples from all stages. Culture-based analysis found CPE and VRE only in environmental samples (11% and 7%, respectively), but Col-E and ESBL-producers in 1–7% and 12–46% of samples from all stages, respectively. Overall, our results showed that ESBL-producers and mcr-carrying Col-E were common in food-producing animals at slaughterhouses, in meat-processing plants and in food items at retail, while CPE and VRE were only found in the environment. The discrepancy between detected carbapenemase genes and isolated CPE emphasizes the need for more sensitive detection methods for CPE monitoring.
Eucalyptol Inhibits Amyloid-β-Induced Barrier Dysfunction in Glucose-Exposed Retinal Pigment Epithelial Cells and Diabetic Eyes
Authors: Kim Dong Yeon , Kang Min-Kyung , Lee Eun-Jung , Kim Yun-Ho , Oh Hyeongjoo , Kim Soo-Il , Oh Su Yeon , Na Woojin , Kang Young-Hee
Published: October 2020

Hyperglycemia elicits tight junction disruption and blood-retinal barrier breakdown, resulting in diabetes-associated vison loss. Eucalyptol is a natural compound found in eucalyptus oil with diverse bioactivities. This study evaluated that eucalyptol ameliorated tight junctions and retinal barrier function in glucose/amyloid-β (Aβ)-exposed human retinal pigment epithelial (RPE) cells and in db/db mouse eyes. RPE cells were cultured in media containing 33 mM glucose or 5 μM Aβ for 4 days in the presence of 1–20 μM eucalyptol. The in vivo animal study employed db/db mice orally administrated with 10 mg/kg eucalyptol. Nontoxic eucalyptol inhibited the Aβ induction in glucose-loaded RPE cells and diabetic mouse eyes. Eucalyptol reversed the induction of tight junction-associated proteins of ZO-1, occludin-1 and matrix metalloproteinases in glucose- or Aβ-exposed RPE cells and in diabetic eyes, accompanying inhibition of RPE detachment from Bruch’s membrane. Adding eucalyptol to glucose- or Aβ-loaded RPE cells, and diabetic mouse eyes reciprocally reversed induction/activation of apoptosis-related bcl-2, bax, cytochrome C/Apaf-1 and caspases. Eucalyptol attenuated the generation of reactive oxygen species and the induction of receptor for advanced glycation end products in Aβ-exposed RPE cells and diabetic eyes. Eucalyptol may ameliorate RPE barrier dysfunction in diabetic eyes through counteracting Aβ-mediated oxidative stress-induced RPE cell apoptosis.
Antioxidant Carbon Nanoparticles Inhibit Fibroblast-Like Synoviocyte Invasiveness and Reduce Disease Severity in a Rat Model of Rheumatoid Arthritis
Authors: Tanner Mark R. , Huq Redwan , Sikkema William K. A. , Nilewski Lizanne G. , Yosef Nejla , Schmitt Cody , Flores-Suarez Carlos P. , Raugh Arielle , Laragione Teresina , Gulko Pércio S. , Tour James M. , Beeton Christine
Published: October 2020

Reactive oxygen species have been involved in the pathogenesis of rheumatoid arthritis (RA). Our goal was to determine the effects of selectively scavenging superoxide (O2•−) and hydroxyl radicals with antioxidant nanoparticles, called poly(ethylene glycol)-functionalized hydrophilic carbon clusters (PEG-HCCs), on the pathogenic functions of fibroblast-like synoviocytes (FLS) from patients with rheumatoid arthritis (RA) and on the progression of an animal model of RA. We used human FLS from patients with RA to determine PEG-HCC internalization and effects on FLS cytotoxicity, invasiveness, proliferation, and production of proteases. We used the pristane-induced arthritis (PIA) rat model of RA to assess the benefits of PEG-HCCs on reducing disease severity. PEG-HCCs were internalized by RA-FLS, reduced their intracellular O2•−, and reduced multiple measures of their pathogenicity in vitro, including proliferation and invasion. In PIA, PEG-HCCs caused a 65% reduction in disease severity, as measured by a standardized scoring system of paw inflammation and caused a significant reduction in bone and tissue damage, and circulating rheumatoid factor. PEG-HCCs did not induce lymphopenia during PIA. Our study demonstrated a role for O2•− and hydroxyl radicals in the pathogenesis of a rat model of RA and showed efficacy of PEG-HCCs in treating a rat model of RA.
Establishment and Application of the Spatial Decomposition Method (SDM) for Tunnels Passing Through Large Karst Caves
Authors: Shi Zhenyue , Wang Qingbiao , Pang Chuming , Yuan Yueming , Wang Fuqiang , Song Hongxu , Liu Jichang , Zhang Zijie , Sun Rongbo , Liu Yan
Published: October 2020

Karst tunnels commonly pass through large karst caves during their construction and operation. Although treatment technologies are relatively mature, a systematic treatment method to guide the selection of treatment technologies is lacking. To solve this problem, a spatial decomposition method (SDM) of large karst caves is proposed that is based on analyzing the spatial relationship between tunnels and karst caves and summarizing the relevant treatment techniques. In this method, the space between the tunnel and the cavern is divided into eight parts using a space dividing line (SDL), which makes the spatial position relationship between the tunnel and cavern more intuitive. A geometric model of the SDM is established, and the numerical values of each geometric parameter are determined by field surveys and drawings. Constructing a three-dimensional spatial diagram by applying relevant parameters to the geometric model provides a reference for selecting a treatment technology. The SDM of the arch top, arch bottom, and two wings matching the treatment technology is proposed. Seven principles of technical selection—namely, safety, convenience, scientificity, sustainability, economy, feasibility, and openness—are mentioned in order to overcome the difficulty of technology selection due to such factors as technological diversity, materials, equipment, and environment. Finally, the SDM is used to solve the problem of the Shangyuan tunnel passing through a large karst cave. The implementation of the SDM in tunnel construction would represent a significant breakthrough and has important engineering value in solving the problem of tunnel passes through large karst caves.
High-Accuracy Location of Microseismic Events in a Strong Inhomogeneous Mining Environment by Optimized Global Full Waveform Inversion
Authors: Wang Yi , Shang Xueyi , Wang Zewei , Gao Rui
Published: October 2020

High-accuracy determination of a microseismic (MS) location is the core task in MS monitoring. In this study, a 3D multi-scale grid Green’s function database, depending on recording wavefield frequency band for the target mining area, is pre-generated based on the reciprocity theorem and 3D spectral element method (SEM). Then, a multi-scale global grid search strategy is performed based on this pre-stored Green’s function database, which can be effectively and hierarchically processed by searching for the spatial location. Numerical wavefield modeling by SEM effectively overcomes difficulties in traditional and simplified ray tracing modeling, such as difficult wavefield amplitude and multi-path modeling in 3D focusing and defusing velocity regions. In addition, as a key step for broadband waveform simulation, the source-time function estimated from a new data-driven singular value decomposition averaged fractional derivative based wavelet function (DD-SVD-FD wavelet) was proposed to generate high-precision synthetic waveforms for better fitting observed broadband waveform than those by simple and traditional source-time function. Combining these sophisticated processing procedures, a new robust grid search and waveform inversion-based location (GSWI location) approach is integrated. In the synthetic test, we discuss and demonstrate the importance of 3D velocity model accuracy to waveform inversion-based location results for a practical MS monitoring configuration. Furthermore, the average location error of the 3D GSWI location for eight real blasting events is only 15.0 m, which is smaller than error from 3D ray tracing-based location (26.2 m) under the same velocity model. These synthetic and field application investigations prove the crucial role of 3D velocity model, finite-frequency travel-time sensitivity kernel characteristics and accurate numerical 3D broadband wavefield modeling for successful MS location in a strong heterogeneous velocity model that are induced by the presence of ore body, host rocks, complex tunnels, and large excavations.
A Simplified CityGML-Based 3D Indoor Space Model for Indoor Applications
Authors: Sun Qun , Zhou Xiaoguang , Hou Dongyang
Published: October 2020

With the continuous development of indoor positioning technology, various indoor applications, such as indoor navigation and emergency rescue, have gradually received widespread attention. Indoor navigation and emergency rescue require access to a variety of indoor space information, such as accurate geometric information, rich semantic information and indoor spatial adjacency information; hence, a suitable 3D indoor model is needed. However, the available models, such as BIM and CityGML, mainly represent geometric and semantic information of indoor spaces, and rarely describe the topological adjacency relationship of interior spaces. To address the requirements of indoor navigation and emergency rescue, a simplified 3D indoor model is proposed in this research. The building components and indoor functional spaces of buildings are described in a simplified way. The geometric and semantic information are described based on CityGML, and the topological relationships of indoor adjacent spaces are represented by CityGML XLinks. While describing the indoor level of detail (LOD) of buildings in detail, the model simplifies building components and indoor spaces, which can preserve the characteristics of indoor spaces to the maximum extent and serve as a basis for indoor applications.
THz Reflective Imaging System Utilizing Broadband Homodyne Amplification for Artifact-Free See-Through Imaging
Authors: Moon Kiwon , Lee Il-Min , Lee Eui Su , Park Kyung Hyun
Published: October 2020

Terahertz (THz) technology offers unique see-through imaging capability for various non-destructive inspection applications. In this work, we implemented a broadband continuous-wave THz imaging system to study technical issues related to the see-through imaging, including frequency-dependent resolution, material loss, and interference-induced artifacts. The interference-induced false contrast and artifacts were observed, which were suppressed by broadband imaging techniques adopting the homodyne signal amplification by interferometric setup to overcome the material loss.
Performance of the RegCM4.6 for High-Resolution Climate and Extreme Simulations over Tibetan Plateau
Authors: Gu Huanghe , Wang Xiaoyan
Published: October 2020

This paper presents an evaluation of the Regional Climate Model version 4.6.1 (RegCM4) at a high-resolution simulation at 10 km applied over the Tibetan Plateau. This simulation covers the period from 1980 to 2010 and is nested in a RegCM4 simulation at 30-km resolution, which is driven by the main European Centre for Medium-Range Weather and Forecasting reanalysis (ERA-Interim reanalysis) dataset. A new daily observational dataset is employed as reference data to evaluate the temperature and precipitation simulations for the inner model domain and the five largest river basins that originated in the Tibetan Plateau (TP) (i.e., the source region of Yangtze River, Yellow River, Mekong River, Salween River, and Brahmaputra River). In comparison with the low-resolution model run (R30), the cold biases for the area-averaged temperature were reduced from −2.5 to −0.1° C and the wet biases in summer mean precipitation were reduced from 58% to 25% in the high-resolution model run (R10). The substantial warming trends and slight wetting trends were basically reproduced by both RegCM4 simulations. Annual mean precipitation trends from both simulations show a better agreement with the observations than the ERA-Interim, which underestimates the annual mean precipitation trends in most regions, whereas both the RegCM4 and ERA-Interim consistently underestimate the annual mean temperature trends when compared with the observations. In addition, the overall improvement in the modeling trends for annual mean temperature and precipitation in R10 is limited when compared with R30. The extreme precipitation was also captured reasonably in both RegCM4 simulations, and the better performance is detected in the R10 simulation. The findings above show that RegCM4 with a high-resolution of 10 km is capable of reproducing the major regional climate features over the TP, but a great deal of uncertainties still exist, especially in the subregion of the Brahmaputra River basin. Thus, the 10-km resolution simulation in RegCM4 may still not be fine enough to resolve the topoclimates over the complex Himalayan terrain in the Brahmaputra River basin.
Diversity of Bioaerosols in Selected Rooms of Two Schools and Antibiotic Resistance of Isolated Staphylococcal Strains (Bydgoszcz, Poland): A Case Study
Authors: Małecka-Adamowicz Marta , Koim-Puchowska Beata , Dembowska Ewa A.
Published: October 2020

The present study is aimed at evaluating microbiological air pollution in libraries, cafeterias and selected classrooms of two schools in Bydgoszcz city, northern Poland and determining the antibiotic resistance of Staphylococcal strains isolated from the indoor air. One of the investigated schools (School A) is located in the very center of the city, in the vicinity of a park, among old houses and stone-lined streets, while the other (School B), among modern residential buildings, close to a street with heavy traffic. In each school, air samples were collected in the morning, always from all three sampling sites, using the MAS-100 sampler. Selective growth media were used for bacteria and mold isolation and quantifying analysis. The antibiotic resistance of the isolated mannitol-positive staphylococci was assessed using the disc diffusion method in accordance with EUCAST recommendations. The highest mean concentration of heterotrophic bacteria was recorded in the cafeterias: 884 CFU m−3 in School A and 1906 CFU m−3 in School B. Molds were the most abundant in the library and cafeteria in School B, where their average concentration exceeded 300 CFU m−3. Cladosporium and Penicillium species prevailed, while Fusarium, Acremonium and Aspergillus were less abundant. Airborne mannitol-positive staphylococci were recorded at low concentrations, ranging from 6 to 11 CFU m−3 on average. According to the taxonomic analysis, Staphylococcus aureus isolates were the most abundant in both schools, followed by S. xylosus, S. haemolyticus and S. saprophyticus. The antibiograms indicated that resistance to erythromycin was common in 62.5% of the isolated staphylococcal strains. Levofloxacin and gentamicin were the most effective antibiotics. No multidrug-resistant strains were identified.
Interdecadal Change in the Relationship between Northern and Southern Hemisphere Meridional Circulation over the Western Pacific Ocean
Authors: Gao Ya , Chen Dong , Wang Huijun
Published: October 2020

The western North Pacific monsoon in the Northern Hemisphere (NH) and the local Hadley circulation in the Southern Hemisphere (SH) are important components of the vertical meridional circulation over the western Pacific Ocean. Here, we define the SH meridional circulation (SHMC) and NH meridional circulation (NHMC) and investigate their relationship over the western Pacific Ocean. Although they are consistent integrally in the climatological circulation, the NHMC and SHMC do not have a positive change relationship but a significantly negative relationship. In addition, this negative correlation experiences an interdecadal change, with one closely related period during 1989–2003 (Period 2, P2) and two weakened related periods during 1979–1988 (Period 1, P1) and 2004–2017 (Period 3, P3). Through the analysis of the meridional wind field at lower and upper levels, we found that the SHMC moves northward during P2, which can result in a close relationship with the NHMC. The possible mechanism is as follows: The Walker circulation strengthened in P2, which strengthened the ascending motion over the western Pacific Ocean, thus inducing the SHMC to strengthen and move northward, resulting in a significantly stronger relationship with the NHMC.
Ammonia Emissions from Differing Manure Storage Facilities at Two Midwestern Free-Stall Dairies
Authors: Grant Richard H. , Boehm Matthew T.
Published: October 2020

Dairies contribute a major portion of agricultural ammonia emissions in the United States. Emissions were monitored over two years from an anaerobic lagoon receiving manure from cows in the milking parlor and holding area in Indiana (IN), USA and a storage basin receiving manure from cows in barns as well as the milking parlor and holding area in Wisconsin (WI), USA. Emissions were monitored using open-path tunable diode lasers, sonic anemometers, and two emission models. The mean annual daily emissions at the WI storage basins (30 µg m−2 s−1) was nearly equal to that at the IN lagoon (27 µg m−2 s−1). The mean annual daily ammonia (NH3) emissions on a per animal basis were greater at the WI basins (33 g NH3 hd−1 d−1; 26 g NH3 AU−1 d−1) (hd = animal; AU = 500 kg animal mass) than at the IN lagoon (9 g NH3 hd−1 d−1; 7 g NH3 AU−1 d−1). Emissions from both storage systems were highest in the summer, lowest in the winter, and similar during the spring and fall. Emissions were strongly correlated with air temperature and weakly correlated with wind conditions. Greater emissions at the WI basins appeared to be related primarily to the characteristics of the stored manure.
Green and Cost-Effective Synthesis of Metallic Nanoparticles by Algae: Safe Methods for Translational Medicine
Authors: Uzair Bushra , Liaqat Ayesha , Iqbal Haroon , Menaa Bouzid , Razzaq Anam , Thiripuranathar Gobika , Fatima Rana Nosheen , Menaa Farid
Published: October 2020

Metal nanoparticles (NPs) have received much attention for potential applications in medicine (mainly in oncology, radiology and infectiology), due to their intriguing chemical, electronical, catalytical, and optical properties such as surface plasmon resonance (SPR) effect. They also offer ease in controlled synthesis and surface modification (e.g., tailored properties conferred by capping/protecting agents including N-, P-, COOH-, SH-containing molecules and polymers such as thiol, disulfide, ammonium, amine, and multidentate carboxylate), which allows (i) tuning their size and shape (e.g., star-shaped and/or branched) (ii) improving their stability, monodispersity, chemical miscibility, and activity, (iii) avoiding their aggregation and oxidation over time, (iv) increasing their yield and purity. The bottom-up approach, where the metal ions are reduced in the NPs grown in the presence of capping ligands, has been widely used compared to the top-down approach. Besides the physical and chemical synthesis methods, the biological method is gaining much consideration. Indeed, several drawbacks have been reported for the synthesis of NPs via physical (e.g., irradiation, ultrasonication) and chemical (e.g., electrochemisty, reduction by chemicals such as trisodium citrate or ascorbic acid) methods (e.g., cost, and/ortoxicity due to use of hazardous solvents, low production rate, use of huge amount of energy). However, (organic or inorganic) eco-friendly NPs synthesis exhibits a sustainable, safe, and economical solution. Thereby, a relatively new trend for fast and valuable NPs synthesis from (live or dead) algae (i.e., microalgae, macroalgae and cyanobacteria) has been observed, especially because of its massive presence on the Earth’s crust and their unique properties (e.g., capacity to accumulate and reduce metallic ions, fast propagation). This article discusses the algal-mediated synthesis methods (either intracellularly or extracellularly) of inorganic NPs with special emphasis on the noblest metals, i.e., silver (Ag)- and gold (Au)-derived NPs. The key factors (e.g., pH, temperature, reaction time) that affect their biosynthesis process, stability, size, and shape are highlighted. Eventually, underlying molecular mechanisms, nanotoxicity and examples of major biomedical applications of these algal-derived NPs are presented.
The Polar Lipidome of Cultured Emiliania huxleyi: A Source of Bioactive Lipids with Relevance for Biotechnological Applications
Authors: Aveiro Susana S. , Melo Tânia , Figueiredo Ana , Domingues Pedro , Pereira Hugo , Maia Inês B. , Silva Joana , Domingues M. Rosário , Nunes Cláudia , Moreira Ana S. P.
Published: October 2020

Polar lipids from microalgae have aroused greater interest as a natural source of omega-3 (n-3) polyunsaturated fatty acids (PUFA), an alternative to fish, but also as bioactive compounds with multiple applications. The present study aims to characterize the polar lipid profile of cultured microalga Emiliania huxleyi using hydrophilic interaction liquid chromatography coupled with high-resolution mass spectrometry (HILIC–MS) and fatty acids (FA) analysis by gas chromatography (GC–MS). The lipidome of E. huxleyi revealed the presence of distinct n-3 PUFA (40% of total FA), namely docosahexaenoic acid (22:6n-3) and stearidonic acid (18:4n-3), which give this microalga an increased commercial value as a source of n-3 PUFA present in the form of polar lipids. A total of 134 species of polar lipids were identified and some of these species, particularly glycolipids, have already been reported for their bioactive properties. Among betaine lipids, the diacylglyceryl carboxyhydroxymethylcholine (DGCC) class is the least reported in microalgae. For the first time, monomethylphosphatidylethanolamine (MMPE) has been found in the lipidome of E. huxleyi. Overall, this study highlights the potential of E. huxleyi as a sustainable source of high-value polar lipids that can be exploited for different applications, namely human and animal nutrition, cosmetics, and pharmaceuticals.
Classical Examples of the Concept of the ASIA Syndrome
Authors: Borba Vânia , Malkova Anna , Basantsova Natalia , Halpert Gilad , Andreoli Laura , Tincani Angela , Amital Howard , Shoenfeld Yehuda
Published: October 2020

Autoimmune/inflammatory syndrome induced by adjuvants (ASIA) was first introduced in 2011 by Shoenfeld et al. and encompasses a cluster of related immune mediated diseases, which develop among genetically prone individuals as a result of adjuvant agent exposure. Since the recognition of ASIA syndrome, more than 4400 documented cases have been reported so far, illustrated by heterogeneous clinical manifestations and severity. In this review, five enigmatic conditions, including sarcoidosis, Sjögren’s syndrome, undifferentiated connective tissue disease, silicone implant incompatibility syndrome (SIIS), and immune-related adverse events (irAEs), are defined as classical examples of ASIA. Certainly, these disorders have been described after an adjuvant stimulus (silicone implantation, drugs, infections, metals, vaccines, etc.) among genetically predisposed individuals (mainly the HLA-DRB1 and PTPN22 gene), which induce an hyperstimulation of the immune system resulting in the production of autoantibodies, eventually leading to the development of autoimmune diseases. Circulating autonomic autoantibodies in the sera of patients with silicone breast implants, as well as anatomopathological aspects of small fiber neuropathy in their skin biopsies have been recently described. To our knowledge, these novel insights serve as a common explanation to the non-specific clinical manifestations reported in patients with ASIA, leading to the redefinition of the ASIA syndrome diagnostic criteria.
Decrypting UFMylation: How Proteins Are Modified with UFM1
Authors: Banerjee Sayanika , Kumar Manoj , Wiener Reuven
Published: October 2020

Besides ubiquitin (Ub), humans have a set of ubiquitin-like proteins (UBLs) that can also covalently modify target proteins. To date, less is known about UBLs than Ub and even less is known about the UBL called ubiquitin-fold modifier 1 (UFM1). Currently, our understanding of protein modification by UFM1 (UFMylation) is like a jigsaw puzzle with many missing pieces, and in some cases it is not even clear whether these pieces of data are in the right place. Here we review the current data on UFM1 from structural biology to biochemistry and cell biology. We believe that the physiological significance of protein modification by UFM1 is currently underestimated and there is more to it than meets the eye.
S-Methylcysteine (SMC) Ameliorates Intestinal, Hepatic, and Splenic Damage Induced by Cryptosporidium parvum Infection Via Targeting Inflammatory Modulators and Oxidative Stress in Swiss Albino Mice
Authors: Elmahallawy Ehab Kotb , Elshopakey Gehad E. , Saleh Amira A. , Agil Ahmad , El-Morsey Ahmed , EL-shewehy Dina M. M. , Sad Ahmed S. , Yanai Tokuma , Abdo Walied
Published: October 2020

Cryptosporidiosis has been proposed to be one of the major causes of diarrhoeal disease in humans worldwide that possesses zoonotic concern. Thereby, this study investigated the potential effects of s-Methylcysteine (SMC) on the parasite in vivo followed by the measurement of cytokines, oxidative stress parameters, and an investigation of the major histopathological changes. Sixty male Swiss albino mice weighing 20–25 g were allocated equally into five groups and orally administered saline only (control), SMC only (SMC50) (50 mg/kg b.w.), and 104Cryptosporidium parvum oocysts per mouse via an esophageal tube (C + ve untreated). The fourth and fifth groups (C + SMC25, C + SMC50) administrated 104C. parvum oocysts combined with SMC25 (low dose) and 50 (high dose) mg/kg b.w., respectively. At days 7 and 14 post-infection (PI), the feces was collected from each group in order to count C. parvum oocysts. After two weeks of treatment, the animals were euthanized and the serum was collected for biochemical analysis. Next, the intestinal, spleen, and liver sections were dissected for histopathological examination. The results revealed lower oocyst numbers in the C + SMC25 and C + SMC50 groups compared to the infected untreated group. Moreover, higher doses of SMC treatment significantly reduced the enteritis induced by C. parvum in a dose-dependent manner. The hepatic lesions were also mitigated as demonstrated in C + SMC25 and C + SMC50 groups unlike the infected group via lowering the serum alanine aminotransferase (ALT), aspartate aminotransferase (AST), and alkaline phosphatase (ALP) enzymes and increasing albumin and globulin serum levels. SMC administration also reduced cytokines production (SAP, TNF-α, IL-6, and IFN-γ) mediated by Cryptosporidium infection in contrast to the infected untreated group. There were marked lymphoid depletion and amyloidosis observed in the infected untreated group, while the treated groups showed obvious increase in the lymphoid elements. Moreover, the scoring of intestinal parasites, hepatic, and splenic lesions in the SMC-treated groups exhibited significantly lower pathological lesions in different organs in a dose-dependent manner, compared to the infected untreated group. Our results also revealed a significant change in the malondialdehyde content with an elevation of glutathione and superoxide dismutase in the intestines collected from C + SMC25 and C + SMC50 mice relative to the untreated group. Taken together, our results indicated that SMC could be a promising effective compound for treating and declining C. parvum infestation via restoring structural alterations in different tissues, enhancing antioxidant enzymes, and suppressing the cytokines liberation.
Development of a Multifunctional Bioerodible Nanocomposite Containing Metronidazole and Curcumin to Apply on L-PRF Clot to Promote Tissue Regeneration in Dentistry
Authors: Murgia Denise , Angellotti Giuseppe , Conigliaro Alice , Carfi Pavia Francesco , D'Agostino Fabio , Contardi Marco , Mauceri Rodolfo , Alessandro Riccardo , Campisi Giuseppina , De Caro Viviana
Published: October 2020

Teeth extractions are often followed by alveolar bone reabsorption, although an adequate level of bone is required for reliable rehabilitations by dental implants. Leukocyte and platelet-rich fibrin (L-PRF) has been widely applied in regenerative procedures and with antibiotic and antioxidant agents could play an essential role in hard and soft tissue healing. In this work, a nanocomposite (Sponge-C-MTR) consisting of a hyaluronate-based sponge loaded with metronidazole (MTR) and nanostructured lipid carriers containing curcumin (CUR-NLC) was designed to be wrapped in the L-PRF™ membrane in the post-extraction sockets and characterized. CUR-NLCs, obtained by homogenization followed by high-frequency sonication of the lipid mixture, showed loading capacity (5% w/w), drug recovery (95% w/w), spherical shape with an average particle size of 112.0 nm, and Zeta potential of −24 mV. Sponge-C-MTR was obtained by entrapping CUR-NLC in a hydrophilic matrix by a freeze-drying process, and physico-chemical and cytocompatibility properties were evaluated. Moreover, the aptitude of CUR and MTR to the penetrate and/or permeate both L-PRF™ and porcine buccal tissue was assessed, highlighting MTR penetration and CUR accumulation promoted by the system. The results positively support the action of nanocomposite in dental tissues regeneration when applied together with the L-PRF™.
Brain Magnetic Resonance Findings in 117 Children with Autism Spectrum Disorder under 5 Years Old
Authors: Rochat Magali Jane , Distefano Giacomo , Maffei Monica , Toni Francesco , Posar Annio , Scaduto Maria Cristina , Resca Federica , Cameli Cinzia , Bacchelli Elena , Maestrini Elena , Visconti Paola
Published: October 2020

We examined the potential benefits of neuroimaging measurements across the first 5 years of life in detecting early comorbid or etiological signs of autism spectrum disorder (ASD). In particular, we analyzed the prevalence of neuroradiologic findings in routine magnetic resonance imaging (MRI) scans of a group of 117 ASD children younger than 5 years old. These data were compared to those reported in typically developing (TD) children. MRI findings in children with ASD were analyzed in relation to their cognitive level, severity of autistic symptoms, and the presence of electroencephalogram (EEG) abnormalities. The MRI was rated abnormal in 55% of children with ASD with a significant prevalence in the high-functioning subgroup compared to TD children. We report significant incidental findings of mega cisterna magna, ventricular anomalies and abnormal white matter signal intensity in ASD without significant associations between these MRI findings and EEG features. Based on these results we discuss the role that brain MRI may play in the diagnostic procedure of ASD.
Electrically Conductive MXene-Coated Glass Fibers for Damage Monitoring in Fiber-Reinforced Composites
Authors: Hatter Christine B. , Sarycheva Asia , Levitt Ariana , Anasori Babak , Nataraj Latha , Gogotsi Yury
Published: October 2020

Multifunctional fiber-reinforced composites play a significant role in advanced aerospace and military applications due to their high strength and toughness resulting in superior damage tolerance. However, early detection of structural changes prior to visible damage is critical for extending the lifetime of the part. MXenes, an emerging class of two-dimensional (2D) nanomaterials, possess hydrophilic surfaces, high electrical conductivity and mechanical properties that can potentially be used to identify damage within fiber-reinforced composites. In this work, conductive Ti3C2Tx MXene flakes were successfully transferred onto insulating glass fibers via oxygen plasma treatment improving adhesion. Increasing plasma treatment power, time and coating layers lead to a decrease in electrical resistance of MXene-coated fibers. Optimized uniformity was achieved using an alternating coating approach with smaller flakes helping initiate and facilitate adhesion of larger flakes. Tensile testing with in-situ electrical resistance tracking showed resistances as low as 1.8 kΩ for small-large flake-coated fiber bundles before the break. Increased resistance was observed during testing, but due to good adhesion between the fiber and MXene, most connective pathways within fiber bundles remained intact until fiber bundles were completely separated. These results demonstrate a potential use of MXene-coated glass fibers in damage-sensing polymer-matrix composites.
Aptamers: Novel Therapeutics and Potential Role in Neuro-Oncology
Authors: Amero Paola , Khatua Soumen , Rodriguez-Aguayo Cristian , Lopez-Berestein Gabriel
Published: October 2020

A relatively new paradigm in cancer therapeutics is the use of cancer cell–specific aptamers, both as therapeutic agents and for targeted delivery of anticancer drugs. After the first therapeutic aptamer was described nearly 25 years ago, and the subsequent first aptamer drug approved, many efforts have been made to translate preclinical research into clinical oncology settings. Studies of aptamer-based technology have unveiled the vast potential of aptamers in therapeutic and diagnostic applications. Among pediatric solid cancers, brain tumors are the leading cause of death. Although a few aptamer-related translational studies have been performed in adult glioblastoma, the use of aptamers in pediatric neuro-oncology remains unexplored. This review will discuss the biology of aptamers, including mechanisms of targeting cell surface proteins, various modifications of aptamer structure to enhance therapeutic efficacy, the current state and challenges of aptamer use in neuro-oncology, and the potential therapeutic role of aptamers in pediatric brain tumors.
Novel Concepts of Treatment for Patients with Myelofibrosis and Related Neoplasms
Authors: Bose Prithviraj , Masarova Lucia , Verstovsek Srdan
Published: October 2020

Janus kinase (JAK) inhibition forms the cornerstone of the treatment of myelofibrosis (MF), and the JAK inhibitor ruxolitinib is often used as a second-line agent in patients with polycythemia vera (PV) who fail hydroxyurea (HU). In addition, ruxolitinib continues to be studied in patients with essential thrombocythemia (ET). The benefits of JAK inhibition in terms of splenomegaly and symptoms in patients with MF are undeniable, and ruxolitinib prolongs the survival of persons with higher risk MF. Despite this, however, “disease-modifying” effects of JAK inhibitors in MF, i.e., bone marrow fibrosis and mutant allele burden reduction, are limited. Similarly, in HU-resistant/intolerant PV, while ruxolitinib provides excellent control of the hematocrit, symptoms and splenomegaly, reduction in the rate of thromboembolic events has not been convincingly demonstrated. Furthermore, JAK inhibitors do not prevent disease evolution to MF or acute myeloid leukemia (AML). Frontline cytoreductive therapy for PV generally comprises HU and interferons, which have their own limitations. Numerous novel agents, representing diverse mechanisms of action, are in development for the treatment of these three classic myeloproliferative neoplasms (MPNs). JAK inhibitor-based combinations, all of which are currently under study for MF, have been covered elsewhere in this issue. In this article, we focus on agents that have been studied as monotherapy in patients with MF, generally after JAK inhibitor resistance/intolerance, as well as several novel compounds in development for PV/ET.
Advances in Natural or Synthetic Nanoparticles for Metastatic Melanoma Therapy and Diagnosis
Authors: Arasi Maria Beatrice , Pedini Francesca , Valentini Sonia , Felli Nadia , Felicetti Federica
Published: October 2020

Advanced melanoma is still a major challenge in oncology. In the early stages, melanoma can be treated successfully with surgery and the survival rate is high, nevertheless the survival rate drops drastically after metastasis dissemination. The identification of parameters predictive of the prognosis to support clinical decisions and of new efficacious therapies are important to ensure patients the best possible prognosis. Recent progress in nanotechnology allowed the development of nanoparticles able to protect drugs from degradation and to deliver the drug to the tumor. Modification of the nanoparticle surface by specific molecules improves retention and accumulation in the target tissue. In this review, we describe the potential role of nanoparticles in advanced melanoma treatment and discuss the current efforts of designing polymeric nanoparticles for controlled drug release at the site upon injection. In addition, we highlight the advances as well as the challenges of exosome-based nanocarriers as drug vehicles. We place special focus on the advantages of these natural nanocarriers in delivering various cargoes in advanced melanoma treatment. We also describe the current advances in knowledge of melanoma-related exosomes, including their biogenesis, molecular contents and biological functions, focusing our attention on their utilization for early diagnosis and prognosis in melanoma disease.
CD99–PTPN12 Axis Suppresses Actin Cytoskeleton-Mediated Dimerization of Epidermal Growth Factor Receptor
Authors: Lee Kyoung-Jin , Kim Yuri , Kim Min Seo , Ju Hyun-Mi , Choi Boyoung , Lee Hansoo , Jeoung Dooil , Moon Ki-Won , Kang Dongmin , Choi Jiwon , Yook Jong In , Hahn Jang-Hee
Published: October 2020

The epidermal growth factor receptor (EGFR), a member of ErbB receptor tyrosine kinase (RTK) family, is activated through growth factor-induced reorganization of the actin cytoskeleton and subsequent dimerization. We herein explored the molecular mechanism underlying the suppression of ligand-induced EGFR dimerization by CD99 agonists and its relevance to tumor growth in vivo. Epidermal growth factor (EGF) activated the formation of c-Src/focal adhesion kinase (FAK)-mediated intracellular complex and subsequently induced RhoA-and Rac1-mediated actin remodeling, resulting in EGFR dimerization and endocytosis. In contrast, CD99 agonist facilitated FAK dephosphorylation through the HRAS/ERK/PTPN12 signaling pathway, leading to inhibition of actin cytoskeletal reorganization via inactivation of the RhoA and Rac1 signaling pathways. Moreover, CD99 agonist significantly suppressed tumor growth in a BALB/c mouse model injected with MDA-MB-231 human breast cancer cells. Taken together, these results indicate that CD99-derived agonist ligand inhibits epidermal growth factor (EGF)-induced EGFR dimerization through impairment of cytoskeletal reorganization by PTPN12-dependent c-Src/FAK inactivation, thereby suppressing breast cancer growth.
Positron Emission Tomography in Merkel Cell Carcinoma
Authors: Sachpekidis Christos , Sidiropoulou Polytimi , Hassel Jessica C. , Drakoulis Nikolaos , Dimitrakopoulou-Strauss Antonia
Published: October 2020

Merkel cell carcinoma (MCC) is a rare neuroendocrine skin malignancy usually arising as a nonspecific nodule on sun-exposed areas of the head and neck. Given the poor prognosis of this aggressive tumor, assessment of disease burden in pre- and post-treatment care may ensure an optimal management with significant implications for patient surveillance and prognosis. Although imaging has established its role in locally advanced or distant metastatic MCC, a standard imaging algorithm is yet to be determined and respective recommendations are mainly based on melanoma. Positron emission tomography/computed tomography (PET/CT) is increasingly evolving as a valuable imaging tool in metastatic or unresectable MCC, mostly utilizing the glucose analogue 18F-fluorodeoxyglucose (18F-FDG) as a radiotracer. Despite being inferior in detecting the disease in its early stages compared to the “gold standard” of sentinel lymph node biopsy, recent evidence suggests an important role for 18F-FDG PET/CT in the routine workup of localized MCC. Moreover, 68Ga-labeled somatostatin analogues have been employed as PET tracers in the field of MCC with promising, yet comparable to 18F-FDG, results. This article provides a structured literature review of the most important studies investigating the role of PET or PET/CT in the clinical practice of MCC.
Efficacy of HDAC Inhibitors Belinostat and Panobinostat against Cisplatin-Sensitive and Cisplatin-Resistant Testicular Germ Cell Tumors
Authors: Lobo João , Guimarães-Teixeira Catarina , Barros-Silva Daniela , Miranda-Gonçalves Vera , Camilo Vânia , Guimarães Rita , Cantante Mariana , Braga Isaac , Maurício Joaquina , Oing Christoph , Honecker Friedemann , Nettersheim Daniel , Looijenga Leendert H. J. , Henrique Rui , Jerónimo Carmen
Published: October 2020

Novel treatment options are needed for testicular germ cell tumor (TGCT) patients, particularly important for those showing or developing cisplatin resistance, the major cause of cancer-related deaths. As TGCTs pathobiology is highly related to epigenetic (de)regulation, epidrugs are potentially effective therapies. Hence, we sought to explore, for the first time, the effect of the two most recently FDA-approved HDAC inhibitors (HDACis), belinostat and panobinostat, in (T)GCT cell lines including those resistant to cisplatin. In silico results were validated in 261 patient samples and differential expression of HDACs was also observed across cell lines. Belinostat and panobinostat reduced cell viability in both cisplatin-sensitive cells (NCCIT-P, 2102Ep-P, and NT2-P) and, importantly, also in matched cisplatin-resistant subclones (NCCIT-R, 2102Ep-R, and NT2-R), with IC50s in the low nanomolar range for all cell lines. Treatment of NCCIT-R with both drugs increased acetylation, induced cell cycle arrest, reduced proliferation, decreased Ki67 index, and increased p21, while increasing cell death by apoptosis, with upregulation of cleaved caspase 3. These findings support the effectiveness of HDACis for treating TGCT patients in general, including those developing cisplatin resistance. Future studies should explore them as single or combination agents.
Exploring Essential Issues for Improving Therapeutic Cancer Vaccine Trial Design
Authors: Baxevanis Constantin N. , Fortis Sotirios P. , Ardavanis Alexandros , Perez Sonia A.
Published: October 2020

Therapeutic cancer vaccines have been at the forefront of cancer immunotherapy for more than 20 years, with promising results in phase I and—in some cases—phase II clinical trials, but with failures in large phase III studies. After dozens of clinical studies, only Dendreon’s dendritic cell vaccine Sipuleucel-T has succeeded in receiving US FDA approval for the treatment of metastatic castrate-resistant prostate cancer. Although scientists working on cancer immunotherapy feel that this is an essential breakthrough for the field, they still expect that new vaccine regimens will yield better clinical benefits compared to the four months prolonged median overall survival (OS) Sipuleucel-T demonstrated in the IMPACT phase III clinical trial. Clinical development of cancer vaccines has been unsuccessful due to failures either in randomized phase II or—even worse—phase III trials. Thus, rigorous re-evaluation of these trials is urgently required in order to redefine aspects and optimize the benefits offered by therapeutic cancer vaccines. The scope of this review is to provide to the reader our thoughts on the key challenges in maximizing the therapeutic potentials of cancer vaccines, with a special focus on issues that touch upon clinical trial design.