bluuebunny/crossref_metadata_2025 huggingface dataset:
A Complementary Herbal Product for Controlling Giardiasis
Authors: Abd-Elhamid Tarek Hamdy , Abdel-Rahman Iman A. M. , Mahmoud Amany Refaat , Allemailem Khaled S. , Almatroudi Ahmad , Fouad Samer S. , Abdella Osama H. , Elshabrawy Hatem A. , El-Kady Asmaa M.
Published: April 2021

Giardiasis is an intestinal protozoal disease caused by Giardia lamblia. The disease became a global health issue due to development of resistance to commonly used drugs. Since many plant-derived products have been used to treat many parasitic infestations, we aimed to assess the therapeutic utility of Artemisia annua (A. annua) for giardiasis. We showed that NO production was significantly reduced whereas serum levels of IL-6, IFN-γ, and TNF-α were elevated in infected hamsters compared to uninfected ones. Additionally, infection resulted in increased numbers of intraepithelial lymphocytes and reduced villi heights, goblet cell numbers, and muscularis externa thickness. We also showed that inducible NO synthase (iNOS) and caspase-3 were elevated in the intestine of infected animals. However, treatment with A. annua significantly reduced the intestinal trophozoite counts and IEL numbers, serum IL-6, IFN-γ, and TNF-α, while increasing NO and restoring villi heights, GC numbers, and ME thickness. Moreover, A. annua treatment resulted in lower levels of caspase-3, which indicates a protective effect from apoptotic cell death. Interestingly, A. annua therapeutic effects are comparable to metronidazole. In conclusion, our results show that A. annua extract is effective in alleviating infection-induced intestinal inflammation and pathological effects, which implies its potential therapeutic utility in controlling giardiasis.
Size-Segregated Atmospheric Humic-Like Substances (HULIS) in Shanghai: Abundance, Seasonal Variation, and Source Identification
Authors: Sun Tianming , Li Rui , Meng Ya , Han Yu , Cheng Hanyun , Fu Hongbo
Published: April 2021

Humic-like substances (HULIS) are of great interest due to their optical and chemical characteristics. In this study, a total of 180 samples of atmospheric particulate matter (PM) of different sizes were collected from summer 2018 to spring 2019, in order to analyze the size distribution, to investigate the seasonal variation and then to identify the key sources of HULIS. The annual mean concentration of HULIS in the total suspended particulates reached 5.12 ± 1.42 μg/m3. The HULIS concentration was extremely higher in winter (8.35 ± 2.06 μg/m3) than in autumn (4.88 ± 0.95 μg/m3), in summer (3.62 ± 1.68 μg/m3) and in spring (3.36 ± 0.99 μg/m3). The average annual ratio of water-soluble organic carbon (WSOC) to OC and the ratio of HULIS to WSOC reached 0.546 ± 0.092 and 0.56 ± 0.06, respectively. Throughout the whole year, the size distributions of WSOC and HULIS-C were relatively smooth. The peaks of WSOC appeared at 1.8~3.2 μm and 0.56~1.0 μm, while the peaks of HULIS-C were located at 3.2~5.6 μm, 1.0~1.8 μm and 0.18~0.32 μm. The distribution of the HULIS particle mode was similar in spring, summer and autumn, while there was a lower proportion of the coarse mode and a higher proportion of the condensation mode in winter. By using the comprehensive analysis of principal component analysis (PCA), air mass backward trajectories (AMBTs) and fire point maps, key sources of WSOC and HULIS in Shanghai were identified as biomass combustion (48.42%), coal combustion (17.49%), secondary formation (16.07%) and vehicle exhaust (5.37%). The remaining part might be contributed by crustal dust sources, marine sources and/or other possible sources. This study provides new insight into the characteristics and size distribution of HULIS in Shanghai, thereby providing a practical base for further modeling.
Occurrence of Reading Skills in a National Age Cohort of Norwegian Children with Down Syndrome: What Characterizes Those Who Develop Early Reading Skills?
Authors: Næss Kari-Anne , Nygaard Egil , Smith Elizabeth
Published: April 2021

Children with Down syndrome are at risk of reading difficulties. Reading skills are crucial for social and academic development, and thus, understanding the nature of reading in this clinical group is important. This longitudinal study investigated the occurrence of reading skills in a Norwegian national age cohort of 43 children with Down syndrome from the beginning of first grade to third grade. Data were collected to determine which characteristics distinguished those who developed early reading skills from those who did not. The children′s decoding skills, phonological awareness, nonverbal mental ability, vocabulary, verbal short-term memory, letter knowledge and rapid automatized naming (RAN) performance were measured annually. The results showed that 18.6% of the children developed early decoding skills by third grade. Prior to onset, children who developed decoding skills had a significantly superior vocabulary and letter knowledge than non-readers after controlling for nonverbal mental abilities. These findings indicate that early specific training that focuses on vocabulary and knowledge of words and letters may be particularly effective in promoting reading onset in children with Down syndrome.
Infectious Morbidity in Pediatric Patients Receiving Neoadjuvant Chemotherapy for Sarcoma
Authors: Willmer Denise , Zöllner Stefan K. , Schaumburg Frieder , Jürgens Heribert , Lehrnbecher Thomas , Groll Andreas H.
Published: April 2021

The purpose of this retrospective, single-center cohort study was to assess the infectious burden in pediatric sarcoma patients during neoadjuvant chemotherapy. The review included all patients with a new diagnosis of Ewing sarcoma, osteosarcoma or soft tissue sarcoma between September 2009 and December 2018 who were enrolled in the EWING 2008, CWS SoTiSaR and EURAMOS clinical trial or registry. Primary endpoints were the occurrence of febrile neutropenia (FN) and microbiologically documented infection (MDI). Parameters with a potential impact on FN and MDI were also analyzed. A total of 170 sarcoma patients (median age: 13 years, range: 0–21; 96 m/74 f) received 948 chemotherapy courses (median: 6; range: 2–8). Of these patients, 58.8% had ≥1 FN episode and 20.6% ≥ 1 MDI. FN occurred in 272/948 courses (28.7%) with fever of unknown origin (FUO) in 231 courses and 45 MDI and 19 clinically documented infections (CDI) occurring in a total of 57 courses. Patients enrolled in EWING 2008 had significantly more FN (p < 0.001), infections (p = 0.02) and MDI (p = 0.035). No infection-related deaths were observed. Younger age, tumor type and localization, and higher median and maximum mucositis grades were significantly associated with higher numbers of FN (p < 0.001), and younger age (p = 0.024) and higher median mucositis grade (p = 0.017) with MDI. The study shows substantial infectious morbidity in sarcoma patients during neoadjuvant chemotherapy treatment and opportunities to improve prevention and management.
Lipidomics as a Diagnostic Tool for Prostate Cancer
Authors: Buszewska-Forajta Magdalena , Pomastowski Paweł , Monedeiro Fernanda , Walczak-Skierska Justyna , Markuszewski Marcin , Matuszewski Marcin , Markuszewski Michał J. , Buszewski Bogusław
Published: April 2021

The main goal of this study was to explore the phospholipid alterations associated with the development of prostate cancer (PCa) using two imaging methods: matrix-assisted laser desorption ionization with time-of-flight mass spectrometer (MALDI-TOF/MS), and electrospray ionization with triple quadrupole mass spectrometer (ESI-QqQ/MS). For this purpose, samples of PCa tissue (n = 40) were evaluated in comparison to the controls (n = 40). As a result, few classes of compounds, namely phosphatidylcholines (PCs), lysophosphatidylcholines (LPCs), sphingomyelins (SMs), and phosphatidylethanolamines (PEs), were determined. The obtained results were evaluated by univariate (Mann–Whitney U-test) and multivariate statistical analysis (principal component analysis, correlation analysis, volcano plot, artificial neural network, and random forest algorithm), in order to select the most discriminative features and to search for the relationships between the responses of these groups of substances, also in terms of the used analytical technique. Based on previous literature and our results, it can be assumed that PCa is linked with both the synthesis of fatty acids and lipid oxidation. Among the compounds, phospholipids, namely PC 16:0/16:1, PC 16:0/18:2, PC 18:0/22:5, PC 18:1/18:2, PC 18:1/20:0, PC 18:1/20:4, and SM d18:1/24:0, were assigned as metabolites with the best discriminative power for the tested groups. Based on the results, lipidomics can be found as alternative diagnostic tool for CaP diagnosis.
The Use of Cabozantinib in Advanced Hepatocellular Carcinoma in Hong Kong—A Territory-Wide Cohort Study
Authors: Wong Jeffrey Sum-Lung , Dong Yawen , Tang Vikki , Leung Thomas , Yeung Cynthia S. Y. , Tai Anna , Law Ada , Shum Tracy , Kwok Gerry Gin-Wai , Li Bryan Cho-Wing , Leung Roland , Chiu Joanne , Ma Ka-Wing , She Wong-Hoi , Tsang Josephine , Cheung Tan-To , Yau Thomas
Published: April 2021

(1) Background: Cabozantinib is approved in sorafenib-exposed advanced hepatocellular carcinoma (aHCC). We evaluated the real-life pattern of use, efficacy, and tolerability of cabozantinib in aHCC. (2) Methods: This territory-wide study included consecutive aHCC patients who received cabozantinib between February 2018 and September 2020 in Hong Kong. The objective response rate (ORR), disease control rate (DCR), overall survival (OS), and adverse events (AE) were assessed. (3) Results: Overall, 42 patients were included. Approximately 83.3% had Child-Pugh A cirrhosis. About 64.3% received cabozantinib as a single agent, and the remaining 35.7% received cabozantinib as an add-on to immune checkpoint inhibitors (ICIs). For single-agent patients, the median follow-up was 6.7 months. The ORR was 3.7%, DCR was 44.4%, and the median OS was 8.28 months. About 74.1% of patients experienced any AEs with 7.4% having grade ≥3 AEs. Among patients who received prior ICIs (n = 16), the ORR was 6.3%, and the median OS was 8.28 months. An exploratory analysis of patients who received cabozantinib as an add-on to ICIs showed an ORR of 6.7% and a median OS of 15.1 months, with 73.3% having any AE and 13.3% having grade ≥3 AEs. (4) Conclusions: Cabozantinib had good anti-tumor activity, survival benefits, and acceptable tolerability in real-life aHCC patients.
RGB-Marking to Identify Patterns of Selection and Neutral Evolution in Human Osteosarcoma Models
Authors: Gambera Stefano , Patiño-Garcia Ana , Alfranca Arantzazu , Garcia-Castro Javier
Published: April 2021

Osteosarcoma (OS) is a highly aggressive tumor characterized by malignant cells producing pathologic bone; the disease presents a natural tendency to metastasize. Genetic studies indicate that the OS genome is extremely complex, presenting signs of macro-evolution, and linear and branched patterns of clonal development. However, those studies were based on the phylogenetic reconstruction of next-generation sequencing (NGS) data, which present important limitations. Thus, testing clonal evolution in experimental models could be useful for validating this hypothesis. In the present study, lentiviral LeGO-vectors were employed to generate colorimetric red, green, blue (RGB)-marking in murine, canine, and human OS. With this strategy, we studied tumor heterogeneity and the clonal dynamics occurring in vivo in immunodeficient NOD.Cg-Prkdcscid-Il2rgtm1Wjl/SzJ (NSG) mice. Based on colorimetric label, tumor clonal composition was analyzed by confocal microscopy, flow cytometry, and different types of supervised and unsupervised clonal analyses. With this approach, we observed a consistent reduction in the clonal composition of RGB-marked tumors and identified evident clonal selection at the first passage in immunodeficient mice. Furthermore, we also demonstrated that OS could follow a neutral model of growth, where the disease is defined by the coexistence of different tumor sub-clones. Our study demonstrates the importance of rigorous testing of the selective forces in commonly used experimental models.
Myelopoiesis during Solid Cancers and Strategies for Immunotherapy
Authors: Wildes Tyler J. , DiVita Dean Bayli , Flores Catherine T.
Published: April 2021

Our understanding of the relationship between the immune system and cancers has undergone significant discovery recently. Immunotherapy with T cell therapies and checkpoint blockade has meaningfully changed the oncology landscape. While remarkable clinical advances in adaptive immunity are occurring, modulation of innate immunity has proven more difficult. The myeloid compartment, including macrophages, neutrophils, and dendritic cells, has a significant impact on the persistence or elimination of tumors. Myeloid cells, specifically in the tumor microenvironment, have direct contact with tumor tissue and coordinate with tumor-reactive T cells to either stimulate or antagonize cancer immunity. However, the myeloid compartment comprises a broad array of cells in various stages of development. In addition, hematopoietic stem and progenitor cells at various stages of myelopoiesis in distant sites undergo significant modulation by tumors. Understanding how tumors exert their influence on myeloid progenitors is critical to making clinically meaningful improvements in these pathways. Therefore, this review will cover recent developments in our understanding of how solid tumors modulate myelopoiesis to promote the formation of pro-tumor immature myeloid cells. Then, it will cover some of the potential avenues for capitalizing on these mechanisms to generate antitumor immunity.
CRISPR-Cas and Its Wide-Ranging Applications: From Human Genome Editing to Environmental Implications, Technical Limitations, Hazards and Bioethical Issues
Authors: Piergentili Roberto , Del Rio Alessandro , Signore Fabrizio , Umani Ronchi Federica , Marinelli Enrico , Zaami Simona
Published: April 2021

The CRISPR-Cas system is a powerful tool for in vivo editing the genome of most organisms, including man. During the years this technique has been applied in several fields, such as agriculture for crop upgrade and breeding including the creation of allergy-free foods, for eradicating pests, for the improvement of animal breeds, in the industry of bio-fuels and it can even be used as a basis for a cell-based recording apparatus. Possible applications in human health include the making of new medicines through the creation of genetically modified organisms, the treatment of viral infections, the control of pathogens, applications in clinical diagnostics and the cure of human genetic diseases, either caused by somatic (e.g., cancer) or inherited (mendelian disorders) mutations. One of the most divisive, possible uses of this system is the modification of human embryos, for the purpose of preventing or curing a human being before birth. However, the technology in this field is evolving faster than regulations and several concerns are raised by its enormous yet controversial potential. In this scenario, appropriate laws need to be issued and ethical guidelines must be developed, in order to properly assess advantages as well as risks of this approach. In this review, we summarize the potential of these genome editing techniques and their applications in human embryo treatment. We will analyze CRISPR-Cas limitations and the possible genome damage caused in the treated embryo. Finally, we will discuss how all this impacts the law, ethics and common sense.
Morphological Heterogeneity of the Endoplasmic Reticulum within Neurons and Its Implications in Neurodegeneration
Authors: Sree Sreesha , Parkkinen Ilmari , Their Anna , Airavaara Mikko , Jokitalo Eija
Published: April 2021

The endoplasmic reticulum (ER) is a multipurpose organelle comprising dynamic structural subdomains, such as ER sheets and tubules, serving to maintain protein, calcium, and lipid homeostasis. In neurons, the single ER is compartmentalized with a careful segregation of the structural subdomains in somatic and neurite (axodendritic) regions. The distribution and arrangement of these ER subdomains varies between different neuronal types. Mutations in ER membrane shaping proteins and morphological changes in the ER are associated with various neurodegenerative diseases implying significance of ER morphology in maintaining neuronal integrity. Specific neurons, such as the highly arborized dopaminergic neurons, are prone to stress and neurodegeneration. Differences in morphology and functionality of ER between the neurons may account for their varied sensitivity to stress and neurodegenerative changes. In this review, we explore the neuronal ER and discuss its distinct morphological attributes and specific functions. We hypothesize that morphological heterogeneity of the ER in neurons is an important factor that accounts for their selective susceptibility to neurodegeneration.
Comparative Transcriptomic Analysis of the Hematopoietic System between Human and Mouse by Single Cell RNA Sequencing
Authors: Gao Shouguo , Wu Zhijie , Kannan Jeerthi , Mathews Liza , Feng Xingmin , Kajigaya Sachiko , Young Neal S.
Published: April 2021

(1) Background: mouse models are fundamental to the study of hematopoiesis, but comparisons between mouse and human in single cells have been limited in depth. (2) Methods: we constructed a single-cell resolution transcriptomic atlas of hematopoietic stem and progenitor cells (HSPCs) of human and mouse, from a total of 32,805 single cells. We used Monocle to examine the trajectories of hematopoietic differentiation, and SCENIC to analyze gene networks underlying hematopoiesis. (3) Results: After alignment with Seurat 2, the cells of mouse and human could be separated by same cell type categories. Cells were grouped into 17 subpopulations; cluster-specific genes were species-conserved and shared functional themes. The clustering dendrogram indicated that cell types were highly conserved between human and mouse. A visualization of the Monocle results provided an intuitive representation of HSPC differentiation to three dominant branches (Erythroid/megakaryocytic, Myeloid, and Lymphoid), derived directly from the hematopoietic stem cell and the long-term hematopoietic stem cells in both human and mouse. Gene regulation was similarly conserved, reflected by comparable transcriptional factors and regulatory sequence motifs in subpopulations of cells. (4) Conclusions: our analysis has confirmed evolutionary conservation in the hematopoietic systems of mouse and human, extending to cell types, gene expression and regulatory elements.
Construction of a Highly Selective Membrane Sensor for the Determination of Cobalt (II) Ions
Authors: Khalil Sabry , El-Sharnouby Mohamed
Published: April 2021

A highly Co (II) liquid ion-selective electrode depending on the reaction of cobalt ions with the reagent 2-(5-Bromo-2-pyridylazo)-5-[N-n-propyl-N-(3-sulfopropyl) amino] aniline is successfully fabricated. The characteristic slope (56.66 mV), the linear range response from 3.4 × 10−8 to 2.4 × 10−2 molar, the detection limit (2.7 × 10−8) molar, the selectivity coefficient toward some metal ions, the time of response (10 s), lifetime (seven months), the pH effect on the sensor potential and the basic analytical parameters were studied. The sensor was used to estimate the concentration of cobalt ions in food products and pharmaceutical formulations. The obtained results of the developed sensor were statistically analyzed and compared with those of other different reported electrodes.
Applying Telemedicine to Multidisciplinary Pediatric Inflammatory Bowel Disease Care
Authors: Michel Hilary K. , Maltz Ross M. , Boyle Brendan , Donegan Amy , Dotson Jennifer L.
Published: April 2021

Multidisciplinary care is essential to the delivery of comprehensive, whole-person care for children and adolescents with inflammatory bowel disease (IBD). Team members may include medical, psychosocial, and ancillary providers as well as patient and family advocates. There is significant variability in how this care is delivered from center to center, though prior to the COVID-19 pandemic, most care occurred during in-person visits. At the onset of the pandemic, medical systems world-wide were challenged to continue delivering high quality, comprehensive care, requiring many centers to turn to telemedicine technology. The aim of this manuscript is to describe the process by which we converted our multidisciplinary pediatric and adolescent IBD visits to a telemedicine model by leveraging technology, a multidisciplinary team, and quality improvement (QI) methods. Finally, we put our experience into context by summarizing the literature on telemedicine in IBD care, with a focus on pediatrics and multidisciplinary care.
A Nanoscale Photonic Crystal Cavity Optomechanical System for Ultrasensitive Motion Sensing
Authors: Xia Ji , Wang Fuyin , Cao Chunyan , Hu Zhengliang , Yang Heng , Xiong Shuidong
Published: April 2021

Optomechanical nanocavities open a new hybrid platform such that the interaction between an optical cavity and mechanical oscillator can be achieved on a nanophotonic scale. Owing to attractive advantages such as ultrasmall mass, high optical quality, small mode volume and flexible mechanics, a pair of coupled photonic crystal nanobeam (PCN) cavities are utilized in this paper to establish an optomechanical nanosystem, thus enabling strong optomechanical coupling effects. In coupled PCN cavities, one nanobeam with a mass meff~3 pg works as an in-plane movable mechanical oscillator at a fundamental frequency of πΩm/2π=4.148 MHz. The other nanobeam couples light to excite optical fundamental supermodes at 1542.858 and 1554.464 nm with a Qo larger than 4 × 104. Because of the optomechanical backaction arising from an optical force, abundant optomechanical phenomena in the unresolved sideband are observed in the movable nanobeam. Moreover, benefiting from the in-plane movement of the flexible nanobeam, we achieved a maximum displacement of the movable nanobeam as 1468 fm/Hz1/2. These characteristics indicate that this optomechanical nanocavity is capable of ultrasensitive motion measurements.
Simulating the Evolution of Business Models for Electricity Recharging Infrastructure Development by 2030: A Case Study for Greece
Authors: Statharas Stergios , Moysoglou Yannis , Siskos Pelopidas , Capros Pantelis
Published: April 2021

It is widely accepted that the market uptake of electric vehicles is essential for the decarbonisation of transport. However, scaling up the roll out of electric vehicles (EV) is challenging considering the lack of charging infrastructure. The latter is, currently, developing in an uneven way across the EU countries. A charging infrastructure with wide coverage addresses range limitations but requires high investment with uncertain returns during the early years of deployment. The aim of this paper is to assess how different policy options affect EV penetration and the involvement of private sector in infrastructure deployment. We propose a mathematical programming model of the decision problem and the interaction between the actors of EV charging ecosystem and apply it to the case of Greece from the time period until 2030. Greece represents a typical example of a country with ambitious targets for EV penetration by 2030 (10% of the total stock) with limited effort made until now. The results indicate that it is challenging to engage private investors in the early years, even using subsidies; thus, publicly financed infrastructure deployment is important for the first years. In the mid-term, subsidization on the costs of charging points is necessary to positively influence the uptake of private investments. These are mainly attracted from 2025 onwards, after a critical mass of EVs and infrastructure has been deployed.
Insights into Mechanical Behavior and Biological Properties of Chia Seed Mucilage Hydrogels
Authors: Sacco Pasquale , Lipari Sara , Cok Michela , Colella Matilde , Marsich Eleonora , Lopez Francesco , Donati Ivan
Published: April 2021

In this contribution we report insights on the rheological properties of chia (Salvia hispanica) seed mucilage hydrogels. Creep experiments performed in steady state conditions allowed calculation of Newtonian viscosities for chia hydrogels with different polymer concentration, pointing at inter-chain interactions as the main responsible for the different behavior toward network slipping under constant stress. A combination of oscillatory frequency and stress sweep tests highlighted a moderate effect of temperature in influencing hydrogel mechanics. The latter results prompted us to investigate potential biological functions for this set of biomaterials. Lactate Dehydrogenase assay proved the lack of cytotoxicity of chia suspensions toward Human Mesenchymal Stem Cells from adipose tissue used here as a cell model. Differentiation experiments were finally undertaken to verify the influence of chia samples on osteo-induction triggered by chemical differentiation factors. Alkaline Phosphatase enzyme activity assay and Alizarin red staining demonstrated that chia mucilage did not alter in vitro stem cell differentiation. Collectively, this set of experiments revealed an almost inert role associated with chia suspensions, indicating a possible application of chia-based networks as scaffold models to study osteogenesis in vitro.
Leisure-Time Physical Activity before and during Pregnancy Is Associated with Improved Insulin Resistance in Late Pregnancy
Authors: Cai Chenxi , Zhang Zhengxiao , Mcdonald Samantha , Strom Cody , Skow Rachel J. , May Linda E. , Steinback Craig D. , Davenport Margie H.
Published: April 2021

A total of 83 third trimester pregnant women were recruited to examine the role of pre-pregnancy versus late-pregnancy physical activity on maternal insulin resistance. Principal component analysis plots demonstrated a distinction between the high and low Homeostatic Model Assessment for Insulin Resistance (HOMA-IR) groups. The variation was driven primarily by exercise prior to and during pregnancy. Specifically, higher levels of physical activity prior to pregnancy was associated with a lower HOMA-IR and is not modified by other variables. Women who were active prior to pregnancy were more active during pregnancy. These results suggest that being active before pregnancy may be a good strategy for mitigating the risk of insulin resistance during late pregnancy.
Role and Modulation of TRPV1 in Mammalian Spermatozoa: An Updated Review
Authors: Ramal-Sanchez Marina , Bernabò Nicola , Valbonetti Luca , Cimini Costanza , Taraschi Angela , Capacchietti Giulia , Machado-Simoes Juliana , Barboni Barbara
Published: April 2021

Based on the abundance of scientific publications, the polymodal sensor TRPV1 is known as one of the most studied proteins within the TRP channel family. This receptor has been found in numerous cell types from different species as well as in spermatozoa. The present review is focused on analyzing the role played by this important channel in the post-ejaculatory life of spermatozoa, where it has been described to be involved in events such as capacitation, acrosome reaction, calcium trafficking, sperm migration, and fertilization. By performing an exhaustive bibliographic search, this review gathers, for the first time, all the modulators of the TRPV1 function that, to our knowledge, were described to date in different species and cell types. Moreover, all those modulators with a relationship with the reproductive process, either found in the female tract, seminal plasma, or spermatozoa, are presented here. Since the sperm migration through the female reproductive tract is one of the most intriguing and less understood events of the fertilization process, in the present work, chemotaxis, thermotaxis, and rheotaxis guiding mechanisms and their relationship with TRPV1 receptor are deeply analyzed, hypothesizing its (in)direct participation during the sperm migration. Last, TRPV1 is presented as a pharmacological target, with a special focus on humans and some pathologies in mammals strictly related to the male reproductive system.
Phage Display Screening of Bovine Antibodies to Foot-and-Mouth Disease Virus and Their Application in a Competitive ELISA for Serodiagnosis
Authors: Jeong Sukyo , Ahn Hyun Joo , Min Kyung Jin , Byun Jae Won , Pyo Hyun Mi , Park Mi Young , Ku Bok Kyung , Nah Jinju , Ryoo Soyoon , Wee Sung Hwan , Kim Sang Jick
Published: April 2021

For serodiagnosis of foot-and-mouth disease virus (FMDV), monoclonal antibody (MAb)-based competitive ELISA (cELISA) is commonly used since it allows simple and reproducible detection of antibody response to FMDV. However, the use of mouse-origin MAb as a detection reagent is questionable, as antibody responses to FMDV in mice may differ in epitope structure and preference from those in natural hosts such as cattle and pigs. To take advantage of natural host-derived antibodies, a phage-displayed scFv library was constructed from FMDV-immune cattle and subjected to two separate pannings against inactivated FMDV type O and A. Subsequent ELISA screening revealed high-affinity scFv antibodies specific to a serotype (O or A) as well as those with pan-serotype specificity. When BvO17, an scFv antibody specific to FMDV type O, was tested as a detection reagent in cELISA, it successfully detected FMDV type O antibodies for both serum samples from vaccinated cattle and virus-challenged pigs with even higher sensitivity than a mouse MAb-based commercial FMDV type O antibody detection kit. These results demonstrate the feasibility of using natural host-derived antibodies such as bovine scFv instead of mouse MAb in cELISA for serological detection of antibody response to FMDV in the susceptible animals.
Nusinersen Modulates Proteomics Profiles of Cerebrospinal Fluid in Spinal Muscular Atrophy Type 1 Patients
Authors: Bianchi Laura , Sframeli Maria , Vantaggiato Lorenza , Vita Gian Luca , Ciranni Annamaria , Polito Francesca , Oteri Rosaria , Gitto Eloisa , Di Giuseppe Fabrizio , Angelucci Stefania , Versaci Antonio , Messina Sonia , Vita Giuseppe , Bini Luca , Aguennouz M’hammed
Published: April 2021

Spinal muscular atrophy (SMA) type 1 is a severe infantile autosomal-recessive neuromuscular disorder caused by a survival motor neuron 1 gene (SMN1) mutation and characterized by progressive muscle weakness. Without supportive care, SMA type 1 is rapidly fatal. The antisense oligonucleotide nusinersen has recently improved the natural course of this disease. Here, we investigated, with a functional proteomic approach, cerebrospinal fluid (CSF) protein profiles from SMA type 1 patients who underwent nusinersen administration to clarify the biochemical response to the treatment and to monitor disease progression based on therapy. Six months after starting treatment (12 mg/5 mL × four doses of loading regimen administered at days 0, 14, 28, and 63), we observed a generalized reversion trend of the CSF protein pattern from our patient cohort to that of control donors. Notably, a marked up-regulation of apolipoprotein A1 and apolipoprotein E and a consistent variation in transthyretin proteoform occurrence were detected. Since these multifunctional proteins are critically active in biomolecular processes aberrant in SMA, i.e., synaptogenesis and neurite growth, neuronal survival and plasticity, inflammation, and oxidative stress control, their nusinersen induced modulation may support SMN improved-expression effects. Hence, these lipoproteins and transthyretin could represent valuable biomarkers to assess patient responsiveness and disease progression.
Upgrading the Topical Delivery of Poorly Soluble Drugs Using Ionic Liquids as a Versatile Tool
Authors: Caparica Rita , Júlio Ana , Fernandes Filipe , Araújo Maria Eduarda M. , Costa João Guilherme , Santos de Almeida Tânia
Published: April 2021

Numerous studies are continuously being carried out in pursuit of formulations with higher performance. Problems such as poor drug solubility, which hinders drug incorporation into delivery systems and bioavailability, or limitations concerning the stability and performance of the formulations may cause difficulties, since solving all these drawbacks at once is a huge challenge. Ionic liquids (ILs), due to their tunable nature, may hypothetically be synthesized for a particular application. Therefore, predicting the impact of a particular combination of ions within an IL in drug delivery could be a useful strategy. Eight ILs, two choline amino acid ILs, two imidazole halogenated ILs, and four imidazole amino acid ILs, were prepared. Their applicability at non-toxic concentrations, for improving solubility and the incorporation of the poorly soluble, ferulic, caffeic, and p-coumaric acids, as well as rutin, into topical emulsions, was assessed. Next, the impact of the ILs on the performance of the formulations was investigated. Our study showed that choosing the appropriate IL leads to a clear upgrade of a topical emulsion, by optimizing multiple features of its performance, such as improving the delivery of poorly soluble drugs, altering the viscosity, which may lead to better sensorial features, and increasing the stability over time.
The Role of Sarcopenic Obesity in Cancer and Cardiovascular Disease: A Synthesis of the Evidence on Pathophysiological Aspects and Clinical Implications
Authors: Silveira Erika Aparecida , da Silva Filho Rômulo Roosevelt , Spexoto Maria Claudia Bernardes , Haghighatdoost Fahimeh , Sarrafzadegan Nizal , de Oliveira Cesar
Published: April 2021

Obesity is globally a serious public health concern and is associated with a high risk of cardiovascular disease (CVD) and various types of cancers. It is important to evaluate various types of obesity, such as visceral and sarcopenic obesity. The evidence on the associated risk of CVD, cancer and sarcopenic obesity, including pathophysiological aspects, occurrence, clinical implications and survival, needs further investigation. Sarcopenic obesity is a relatively new term. It is a clinical condition that primarily affects older adults. There are several endocrine-hormonal, metabolic and lifestyle aspects involved in the occurrence of sarcopenic obesity that affect pathophysiological aspects that, in turn, contribute to CVD and neoplasms. However, there is no available evidence on the role of sarcopenic obesity in the occurrence of CVD and cancer and its pathophysiological interplay. Therefore, this review aims to describe the pathophysiological aspects and the clinical and epidemiological evidence on the role of sarcopenic obesity related to the occurrence and mortality risk of various types of cancer and cardiovascular disease. This literature review highlights the need for further research on sarcopenic obesity to demonstrate the interrelation of these various associations.
EBI2 Is Temporarily Upregulated in MO3.13 Oligodendrocytes during Maturation and Regulates Remyelination in the Organotypic Cerebellar Slice Model
Authors: Velasco-Estevez Maria , Koch Nina , Klejbor Ilona , Laurent Stephane , Dev Kumlesh K. , Szutowicz Andrzej , Sailer Andreas W. , Rutkowska Aleksandra
Published: April 2021

The EBI2 receptor regulates the immune system and is expressed in various immune cells including B and T lymphocytes. It is also expressed in astrocytes in the central nervous system (CNS) where it regulates pro-inflammatory cytokine release, cell migration and protects from chemically induced demyelination. Its signaling and expression are implicated in various diseases including multiple sclerosis, where its expression is increased in infiltrating immune cells in the white matter lesions. Here, for the first time, the EBI2 protein in the CNS cells in the human brain was examined. The function of the receptor in MO3.13 oligodendrocytes, as well as its role in remyelination in organotypic cerebellar slices, were investigated. Human brain sections were co-stained for EBI2 receptor and various markers of CNS-specific cells and the human oligodendrocyte cell line MO3.13 was used to investigate changes in EBI2 expression and cellular migration. Organotypic cerebellar slices prepared from wild-type and cholesterol 25-hydroxylase knock-out mice were used to study remyelination following lysophosphatidylcholine (LPC)-induced demyelination. The data showed that EBI2 receptor is present in OPCs but not in myelinating oligodendrocytes in the human brain and that EBI2 expression is temporarily upregulated in maturing MO3.13 oligodendrocytes. Moreover, we show that migration of MO3.13 cells is directly regulated by EBI2 and that its signaling is necessary for remyelination in cerebellar slices post-LPC-induced demyelination. The work reported here provides new information on the expression and role of EBI2 in oligodendrocytes and myelination and provides new tools for modulation of oligodendrocyte biology and therapeutic approaches for demyelinating diseases.
Academic Activities Recommendation System for Sustainable Education in the Age of COVID-19
Authors: Villegas-Ch. William , Sánchez-Viteri Santiago , Román-Cañizares Milton
Published: April 2021

Currently, universities are going through a critical moment due to the coronavirus disease in 2019. To prevent its spread, countries have declared quarantines and isolation in all sectors of society. This has caused many problems in the learning of students, since, when moving from a face-to-face educational model to a remote model, several academic factors such as psychological, financial, and methodological have been overlooked. To exactly identify the variables and causes that affect learning, in this work a data analysis model using a Hadoop framework is proposed. By processing the data, it is possible to identify and classify students to determine the problems they present in different learning activities. The results are used by an artificial intelligence system that takes student information and converts it into knowledge, evaluates the academic performance problems they present, and determines what type of activity aligns with the students. The artificial intelligence system processes the information and recommends activities that focus on each student’s abilities and needs. The integration of these systems to universities creates an adaptive educational model that responds to the new challenges of society.
Synthesis and Characterisation of Molecular Polarised-Covalent Thorium-Rhenium and -Ruthenium Bonds
Authors: Ostrowski Joseph P. A. , Wooles Ashley J. , Liddle Stephen T.
Published: April 2021

Separate reactions of [Th{N(CH2CH2NSiMe2But)2(CH2CH2NSi(Me)(But)(μ-CH2)]2 (1) with [Re(η5-C5H5)2(H)] (2) or [Ru(η5-C5H5)(H)(CO)2] (3) produced, by alkane elimination, [Th(TrenDMBS)Re(η5-C5H5)2] (ThRe, TrenDMBS = {N(CH2CH2NSiMe2But)3}3-), and [Th(TrenDMBS)Ru(η5-C5H5)(CO)2] (ThRu), which were isolated in crystalline yields of 71% and 62%, respectively. Complex ThRe is the first example of a molecular Th-Re bond to be structurally characterised, and ThRu is only the second example of a structurally authenticated Th-Ru bond. By comparison to isostructural U-analogues, quantum chemical calculations, which are validated by IR and Raman spectroscopic data, suggest that the Th-Re and Th-Ru bonds reported here are more ionic than the corresponding U-Re and U-Ru bonds.
Nectar Uptake of a Long-Proboscid Prosoeca Fly (Nemestrinidae)—Proboscis Morphology and Flower Shape
Authors: Krenn Harald W. , Karolyi Florian , Lampert Peter , Melin Annalie , Colville Jonathan F.
Published: April 2021

Several Prosoeca (Nemestinidae) species use a greatly elongated proboscis to drink nectar from long-tubed flowers. We studied morphological adaptations for nectar uptake of Prosoecamarinusi that were endemic to the Northern Cape of South Africa. Our study site was a small isolated area of semi-natural habitat, where the long-tubed flowers of Babiana vanzijliae (Iridaceae) were the only nectar source of P. marinusi, and these flies were the only insects with matching proboscis. On average, the proboscis measured 32.63 ± 2.93 mm in length and less than 0.5 mm in diameter. The short labella at the tip are equipped with pseudotracheae that open at the apical margin, indicating that nectar is extracted out of the floral tube with closed labella. To quantify the available nectar resources, measurements of the nectar volume were taken before the flies were active and after observed flower visits. On average, an individual fly took up approximately 1 µL of nectar per flower visit. The measured nectar quantities and the flower geometry allowed estimations of the nectar heights and predictions of necessary proboscis lengths to access nectar in a range of flower tube lengths.
An Analytic Approach for Pricing American Options with Regime Switching
Authors: Chan Leunglung , Zhu Song-Ping
Published: April 2021

This paper investigates the American option price in a two-state regime-switching model. The dynamics of underlying are driven by a Markov-modulated Geometric Wiener process. That means the interest rate, the appreciation rate, and the volatility of underlying rely on hidden states of the economy which can be interpreted in terms of Markov chains. By means of the homotopy analysis method, an explicit formula for pricing two-state regime-switching American options is presented.
Special Solicitude: Religious Freedom at America’s Public Universities
Authors: Thro William E.
Published: April 2021

Rejecting the Obama Administration’s argument that the First Amendment requires identical treatment for religious organizations and secular organizations, the Supreme Court held such a “result is hard to square with the text of the First Amendment itself, which gives special solicitude to the rights of religious organizations.” (Hosanna-Tabor, 565 U.S. at 189). This “special solicitude” guarantees religious freedom from the government in all aspects of society, but particularly on public university campuses. At a minimum, religious expression and religious organizations must have equal rights with secular expression and secular organizations. In some instances, religious expression and religious expression may have greater rights. The Court’s 2020 decisions in Espinoza v. Montana Department of Revenue, and Our Lady of Guadalupe School v. Morrissey-Berru, reinforce and expand the “special solicitude” of religion. Indeed, Espinoza and Our Lady have profound implications for student religious groups at America’s public campuses. This article examines religious freedom at America’s public universities. This article has three parts. First, it offers an overview of religious freedom prior to Espinoza and Our Lady. Second, it briefly discusses those two cases. Third, it explores the implications of those decisions on America’s public campuses.
A New Model to Identify the Reliability and Trust of Internet Banking Users Using Fuzzy Theory and Data-Mining
Authors: Bekamiri Hamid , Ghasempour Ganji Seyedeh Fatemeh , Simonetti Biagio , Seno Seyed Amin Hosseini
Published: April 2021

As a result of changes in approach from traditional to virtual banking system, security in data exchange has become more important; thus, it seems essentially necessary to present a pattern based on smart models in order to reduce fraud in this field. A new algorithm has been provided in this article to improve security and to specify the limits of giving special services to Internet banking users in order to pave appropriate ground for virtual banking. In addition to identifying behavioral models of customers, this algorithm compares the behaviors of any customer with this model and finally computes the rate of trust in customer’s behavior. The hybrid data-mining and knowledge based structure has been adapted in this algorithm according to fuzzy systems. In this research, qualitative data was gathered from interviews with banking experts, analyzed by Expert Choice to identify the most important variables of customer behavior analysis, and to analyze customer behavior and customer bank Internet transaction data for a period of one year by MATLAB and Clementine. The results of this survey indicate that the potential of the given structure to recognize the rate of trust in Internet bank user’s behavior might be at reasonable level for experts in this area.
F-Operators for the Construction of Closed Form Solutions to Linear Homogenous PDEs with Variable Coefficients
Authors: Navickas Zenonas , Telksnys Tadas , Marcinkevicius Romas , Cao Maosen , Ragulskis Minvydas
Published: April 2021

A computational framework for the construction of solutions to linear homogenous partial differential equations (PDEs) with variable coefficients is developed in this paper. The considered class of PDEs reads: ∂p∂t−∑j=0m∑r=0njajrtxr∂jp∂xj=0 F-operators are introduced and used to transform the original PDE into the image PDE. Factorization of the solution into rational and exponential parts enables us to construct analytic solutions without direct integrations. A number of computational examples are used to demonstrate the efficiency of the proposed scheme.
Model for the Prediction of Deformations in the Manufacture of Thin-Walled Parts by Wire Arc Additive Manufacturing Technology
Authors: Casuso Mikel , Veiga Fernando , Suárez Alfredo , Bhujangrao Trunal , Aldalur Eider , Artaza Teresa , Amondarain Jaime , Lamikiz Aitzol
Published: April 2021

Gas Metal Arc Welding (GMAW) is a manufacturing technology included within the different Wire Arc Additive Manufacturing alternatives. These technologies have been generating great attention among scientists in recent decades. Its main qualities that make it highly productive with a large use of material with relatively inexpensive machine solutions make it a very advantageous technology. This paper covers the application of this technology for the manufacture of thin-walled parts. A finite element model is presented for estimating the deformations in this type of parts. This paper presents a simulation model that predicts temperatures with less than 5% error and deformations of the final part that, although quantitatively has errors of 20%, qualitatively allows to know the deformation modes of the part. Knowing the part areas subject to greater deformation may allow the future adaptation of deposition strategies or redesigns for their adaptation. These models are very useful both at a scientific and industrial level since when we find ourselves with a technology oriented to Near Net Shape (NNS) manufacturing where deformations are critical for obtaining the final part in a quality regime.
Can Markerless Pose Estimation Algorithms Estimate 3D Mass Centre Positions and Velocities during Linear Sprinting Activities?
Authors: Needham Laurie , Evans Murray , Cosker Darren P. , Colyer Steffi L.
Published: April 2021

The ability to accurately and non-invasively measure 3D mass centre positions and their derivatives can provide rich insight into the physical demands of sports training and competition. This study examines a method for non-invasively measuring mass centre velocities using markerless human pose estimation and Kalman smoothing. Marker (Qualysis) and markerless (OpenPose) motion capture data were captured synchronously for sprinting and skeleton push starts. Mass centre positions and velocities derived from raw markerless pose estimation data contained large errors for both sprinting and skeleton pushing (mean ± SD = 0.127 ± 0.943 and −0.197 ± 1.549 m·s−1, respectively). Signal processing methods such as Kalman smoothing substantially reduced the mean error (±SD) in horizontal mass centre velocities (0.041 ± 0.257 m·s−1) during sprinting but the precision remained poor. Applying pose estimation to activities which exhibit unusual body poses (e.g., skeleton pushing) appears to elicit more erroneous results due to poor performance of the pose estimation algorithm. Researchers and practitioners should apply these methods with caution to activities beyond sprinting as pose estimation algorithms may not generalise well to the activity of interest. Retraining the model using activity specific data to produce more specialised networks is therefore recommended.