bluuebunny/crossref_metadata_2025 huggingface dataset:
Nonlocal Problem for a Third-Order Equation with Multiple Characteristics with General Boundary Conditions
Authors: Khashimov Abdukomil Risbekovich , Smetanová Dana
Published: June 2021

The article considers third-order equations with multiple characteristics with general boundary value conditions and non-local initial data. A regular solution to the problem with known methods is constructed here. The uniqueness of the solution to the problem is proved by the method of energy integrals. This uses the theory of non-negative quadratic forms. The existence of a solution to the problem is proved by reducing the problem to Fredholm integral equations of the second kind. In this case, the method of Green’s function and potential is used.
Seeing Is Believing: Gap Junctions in Motion
Authors: Li Xinbo
Published: June 2021

Gap junctional intercellular communication (GJIC) channels between cells are composed of connexin proteins that form hexamers (connexons) in adjacent plasma membranes [...]
Functions and Regulation of Endogenous Retrovirus Elements during Zygotic Genome Activation: Implications for Improving Somatic Cell Nuclear Transfer Efficiency
Authors: Fu Bo , Ma Hong , Liu Di
Published: June 2021

Endogenous retroviruses (ERVs), previously viewed as deleterious relics of ancestral retrovirus infections, are silenced in the vast majority of cells to minimize the risk of retrotransposition. Counterintuitively, bursts of ERV transcription usually occur during maternal-to-zygotic transition (MZT) in preimplantation embryos; this is regarded as a major landmark event in the zygotic genome activation (ZGA) process, indicating that ERVs play an active part in ZGA. Evolutionarily, the interaction between ERVs and hosts is mutually beneficial. The endogenization of retrovirus sequences rewires the gene regulatory network during ZGA, and ERV repression may lower germline fitness. Unfortunately, owing to various limitations of somatic cell nuclear transfer (SCNT) technology, both developmental arrest and ZGA abnormalities occur in a high percentage of cloned embryos, accompanied by ERV silencing, which may be caused by the activation failure of upstream ERV inducers. In this review, we discuss the functions and regulation of ERVs during the ZGA process and the feasibility of temporal control over ERVs in cloned embryos via exogenous double homeobox (DUX). We hypothesize that further accurate characterization of the ERV-rewired gene regulatory network during ZGA may provide a novel perspective on the development of preimplantation embryos.
Molecular Perspective of Nanoparticle Mediated Therapeutic Targeting in Breast Cancer: An Odyssey of Endoplasmic Reticulum Unfolded Protein Response (UPRER) and Beyond
Authors: Rahman Safikur , Kumar Vijay , Kumar Anuj , Abdullah Tasduq S. , Rather Irfan A. , Jan Arif Tasleem
Published: June 2021

Breast cancer (BC) is the second most frequent cause of death among women. Representing a complex and heterogeneous type of cancer, its occurrence is attributed by both genetic (gene mutations, e.g., BRCA1, BRCA2) and non-genetic (race, ethnicity, etc.) risk factors. The effectiveness of available treatment regimens (small molecules, cytotoxic agents, and inhibitors) decreased due to their poor penetration across biological barriers, limited targeting, and rapid body clearance along with their effect on normal resident cells of bone marrow, gastrointestinal tract, and hair follicles. This significantly reduced their clinical outcomes, which led to an unprecedented increase in the number of cases worldwide. Nanomedicine, a nano-formulation of therapeutics, emerged as a versatile delivering module for employment in achieving the effective and target specific delivery of pharmaceutical payloads. Adoption of nanotechnological approaches in delivering therapeutic molecules to target cells ensures not only reduced immune response and toxicity, but increases the stability of therapeutic entities in the systemic circulation that averts their degradation and as such increased extravasations and accumulation via enhanced permeation and the retention (EPR) effect in target tissues. Additionally, nanoparticle (NP)-induced ER stress, which enhances apoptosis and autophagy, has been utilized as a combative strategy in the treatment of cancerous cells. As nanoparticles-based avenues have been capitalized to achieve better efficacy of the new genera of therapeutics with enhanced specificity and safety, the present study is aimed at providing the fundamentals of BC, nanotechnological modules (organic, inorganic, and hybrid) employed in delivering different therapeutic molecules, and mechanistic insights of nano-ER stress induced apoptosis and autophagy with a perspective of exploring this avenue for use in the nano-toxicological studies. Furthermore, the current scenario of USA FDA approved nano-formulations and the future perspective of nanotechnological based interventions to overcome the existing challenges are also discussed.
Tungsten-Based Catalysts for Environmental Applications
Authors: Can Fabien , Courtois Xavier , Duprez Daniel
Published: June 2021

This review aims to give a general overview of the recent use of tungsten-based catalysts for wide environmental applications, with first some useful background information about tungsten oxides. Tungsten oxide materials exhibit suitable behaviors for surface reactions and catalysis such as acidic properties (mainly Brønsted sites), redox and adsorption properties (due to the presence of oxygen vacancies) and a photostimulation response under visible light (2.6–2.8 eV bandgap). Depending on the operating condition of the catalytic process, each of these behaviors is tunable by controlling structure and morphology (e.g., nanoplates, nanosheets, nanorods, nanowires, nanomesh, microflowers, hollow nanospheres) and/or interactions with other compounds such as conductors (carbon), semiconductors or other oxides (e.g., TiO2) and precious metals. WOx particles can be also dispersed on high specific surface area supports. Based on these behaviors, WO3-based catalysts were developed for numerous environmental applications. This review is divided into five main parts: structure of tungsten-based catalysts, acidity of supported tungsten oxide catalysts, WO3 catalysts for DeNOx applications, total oxidation of volatile organic compounds in gas phase and gas sensors and pollutant remediation in liquid phase (photocatalysis).
Gene Expression Analysis of Environmental Temperature and High-Fat Diet-Induced Changes in Mouse Supraclavicular Brown Adipose Tissue
Authors: Shi Yufeng , Zhai Honglei , John Sharon , Shen Yi-Ting , Ran Yali , Hoang Giang , Chen Miao-Hsueh
Published: June 2021

Obesity, a dysregulation of adipose tissue, is a major health risk factor associated with many diseases. Brown adipose tissue (BAT)-mediated thermogenesis can potentially regulate energy expenditure, making it an attractive therapeutic target to combat obesity. Here, we characterize the effects of cold exposure, thermoneutrality, and high-fat diet (HFD) feeding on mouse supraclavicular BAT (scBAT) morphology and BAT-associated gene expression compared to other adipose depots, including the interscapular BAT (iBAT). scBAT was as sensitive to cold induced thermogenesis as iBAT and showed reduced thermogenic effect under thermoneutrality. While both scBAT and iBAT are sensitive to cold, the expression of genes involved in nutrient processing is different. The scBAT also showed less depot weight gain and more single-lipid adipocytes, while the expression of BAT thermogenic genes, such as Ucp1, remained similar or increased more under our HFD feeding regime at ambient and thermoneutral temperatures than iBAT. Together, these findings show that, in addition to its anatomical resemblance to human scBAT, mouse scBAT possesses thermogenic features distinct from those of other adipose depots. Lastly, this study also characterizes a previously unknown mouse deep neck BAT (dnBAT) depot that exhibits similar thermogenic characteristics as scBAT under cold exposure and thermoneutrality.
Single-Cell Transcriptional Heterogeneity of Lymphatic Endothelial Cells in Normal and Inflamed Murine Lymph Nodes
Authors: Sibler Eliane , He Yuliang , Ducoli Luca , Keller Nadja , Fujimoto Noriki , Dieterich Lothar C. , Detmar Michael
Published: June 2021

The lymphatic system plays a crucial role in immunity and lymph nodes (LNs) undergo drastic remodeling during inflammation. Here, we used single-cell RNA sequencing to investigate transcriptional changes in lymphatic endothelial cells (LECs) in LNs draining naïve and inflamed skin. We found that subsets of LECs lining the different LN sinuses responded individually to skin inflammation, suggesting that they exert distinct functions under pathological conditions. Among the genes dysregulated during inflammation, we confirmed an up-regulation of CD200 in the LECs lining the subcapsular sinus floor with a possible function in immune regulation. Furthermore, by in silico analysis, we predicted numerous possible interactions of LECs with diverse immune cells in the LNs and found similarities in the transcriptional changes of LN LECs in different skin inflammation settings. In summary, we provide an in-depth analysis of the transcriptional landscape of LN LECs in the naïve state and in skin inflammation.
CuxO Nanostructure-Based Gas Sensors for H2S Detection: An Overview
Authors: Navale Sachin , Shahbaz Mehrdad , Majhi Sanjit Manohar , Mirzaei Ali , Kim Hyoun Woo , Kim Sang Sub
Published: June 2021

H2S gas is a toxic and hazardous byproduct of the oil and gas industries. It paralyzes the olfactory nerves, with concentrations above 100 ppm, resulting in loss of smell; prolonged inhalation may even cause death. One of the most important semiconducting metal oxides for the detection of H2S is CuxO (x = 1, 2), which is converted to CuxS upon exposure to H2S, leading to a remarkable modulation in the resistance and appearance of an electrical sensing signal. In this review, various morphologies of CuxO in the pristine form, composites of CuxO with other materials, and decoration/doping of noble metals on CuxO nanostructures for the reliable detection of H2S gas are thoroughly discussed. With an emphasis to the detection mechanism of CuxO-based gas sensors, this review presents findings that are of considerable value as a reference.
Pediatric Palliative Care in the Heart Failure, Ventricular Assist Device and Transplant Populations: Supporting Patients, Families and Their Clinical Teams
Authors: Hope Kyle D. , Bhat Priya N. , Dreyer William J. , Elias Barbara A. , Jump Jaime L. , Santucci Gina , Afonso Natasha S. , Ninemire Margaret R. , Achuff Barbara-Jo , Kritz Erin M. , Gowda Sharada H. , Puri Kriti
Published: June 2021

Heart failure is a life-changing diagnosis for a child and their family. Pediatric patients with heart failure experience significant morbidity and frequent hospitalizations, and many require advanced therapies such as mechanical circulatory support and/or heart transplantation. Pediatric palliative care is an integral resource for the care of patients with heart failure along its continuum. This includes support during the grief of a new diagnosis in a child critically ill with decompensated heart failure, discussion of goals of care and the complexities of mechanical circulatory support, the pensive wait for heart transplantation, and symptom management and psychosocial support throughout the journey. In this article, we discuss the scope of pediatric palliative care in the realm of pediatric heart failure, ventricular assist device (VAD) support, and heart transplantation. We review the limited, albeit growing, literature in this field, with an added focus on difficult conversation and decision support surrounding re-transplantation, HF in young adults with congenital heart disease, the possibility of destination therapy VAD, and the grimmest decision of VAD de-activation.
Optimal Halbach Configuration for Flow-through Immunomagnetic CTC Enrichment
Authors: Stevens Michiel , Liu Peng , Niessink Tom , Mentink Anouk , Abelmann Leon , Terstappen Leon
Published: June 2021

Due to the low frequency of circulating tumor cells (CTC), the standard CellSearch method of enumeration and isolation using a single tube of blood is insufficient to measure treatment effects consistently, or to steer personalized therapy. Using diagnostic leukapheresis this sample size can be increased; however, this also calls for a suitable new method to process larger sample inputs. In order to achieve this, we have optimized the immunomagnetic enrichment process using a flow-through magnetophoretic system. An overview of the major forces involved in magnetophoretic separation is provided and the model used for optimizing the magnetic configuration in flow through immunomagnetic enrichment is presented. The optimal Halbach array element size was calculated and both optimal and non-optimal arrays were built and tested using anti-EpCAM ferrofluid in combination with cell lines of varying EpCAM antigen expression. Experimentally measured distributions of the magnetic moment of the cell lines used for comparison were combined with predicted recoveries and fit to the experimental data. Resulting predictions agree with measured data within measurement uncertainty. The presented method can be used not only to optimize magnetophoretic separation using a variety of flow configurations but could also be adapted to optimize other (static) magnetic separation techniques.
Mobile Learning in Pre-Service Teacher Education: Perceived Usefulness of AR Technology in Primary Education
Authors: Gómez-García Gerardo , Hinojo-Lucena Francisco-Javier , Alonso-García Santiago , Romero-Rodríguez José-María
Published: June 2021

Mobile learning is a resource that can enhance the teaching-learning process of students and improve the training of future teachers. Specifically, augmented reality (AR) technology allows for immersive and experiential learning without the need to leave the classroom. The purposes of this paper were to apply AR technology in the training of future Primary Education teachers and to analyze the perceived usefulness of AR in the classroom by future teachers. A quantitative approach was used based on a design with a control group and two experimental groups with a post-test using a sample of 171 second-year students studying an education degree. The results showed that experimentation with AR promoted a slight increase in student motivation. However, no significant differences were found between the control group and the experimental groups. Finally, the findings allowed us to establish that the implementation of resources such as AR does not differ in the opinion of future teachers about the inclination to implement AR in the classroom.
In-House Validation of an SPE-GC-FID Method for the Detection of Free and Esterified Hydroxylated Minor Compounds in Virgin Olive Oils
Authors: Valli Enrico , Milani Andrea , Srbinovska Ana , Moret Erica , Moret Sabrina , Bendini Alessandra , Moreda Wenceslao , Toschi Tullia Gallina , Lucci Paolo
Published: June 2021

Minor compounds in vegetable oils are distributed between free and esterified forms, and the ratio of these two fractions could represent an important parameter for assessment of oil authenticity. A simple method based on offline SPE-GC-FID for the analysis of free and esterified hydroxylated minor compounds in olive and sunflower oils has been developed and in-house validated. A satisfactory repeatability relative standard deviation (<7.5%) was obtained in all cases. The method, which requires simple instrumentation, allows for reliable quantification in a single chromatographic run with the advantages of minimizing sample manipulation, use of toxic solvents and reagents, and time consumption. The analytical procedure was applied to pure oil samples, including 15 authentic extra virgin olive oils collected from different European countries (Spain, Italy, Greece, and Portugal). Finally, the proposed SPE-GC-FID methodology could detect changes in the ratio between the free and esterified forms in pure extra virgin olive oil when mixed with refined sunflower oil at different percentages of 2, 5, 10, 15, and 20% (w/w) to simulate adulteration.
Physical Properties of Chitosan Films Containing Pomegranate Peel Extracts Obtained by Deep Eutectic Solvents
Authors: Kyriakidou Aikaterini , Makris Dimitris P. , Lazaridou Athina , Biliaderis Costas G. , Mourtzinos Ioannis
Published: June 2021

Pomegranate peel is a byproduct of pomegranate juice production, and is rich in polyphenol compounds. The objective of this study was to investigate the incorporation of pomegranate peel extract in chitosan films. Green deep eutectic solvents (DESs) were used as extraction solvents. Choline chloride (ChCl) and glycerol (Gly) were used as the hydrogen bond acceptor and hydrogen bond donor, respectively; the molar ratio of the DES ingredients, ChCl:Gly, was 1:11. The extraction process was optimized by deploying response surface methodology. Under the optimized conditions, the extraction yield in total polyphenols amounted to 272.98 mg of gallic acid equivalents per g of dry matter and, for total flavonoids, 20.12 mg of quercetin equivalents per g of dry matter, with a liquid to solid ratio of 47 mL g−1, time of 70 min, and 30% (v/v) water concentration in the DES. Afterwards, composite chitosan films were prepared by using five different formulations; the DES containing extract was incorporated as a plasticizer in the chitosan films. Specimens of every recipe were submitted to large deformation tensile testing in Texture Analyzer. Furthermore, water sorption behavior and color parameters of the films were determined.
Analysis of Geotagging Behavior: Do Geotagged Users Represent the Twitter Population?
Authors: Karami Amir , Kadari Rachana Redd , Panati Lekha , Nooli Siva Prasad , Bheemreddy Harshini , Bozorgi Parisa
Published: June 2021

Twitter’s APIs are now the main data source for social media researchers. A large number of studies have utilized Twitter data for diverse research interests. Twitter users can share their precise real-time location, and Twitter APIs can provide this information as longitude and latitude. These geotagged Twitter data can help to study human activities and movements for different applications. Compared to the mostly small-scale data samples in different domains, such as social science, collecting geotagged data offers large samples. There is a fundamental question whether geotagged users can represent non-geotagged users. While some studies have investigated the question from different perspectives, they did not investigate profile information and the contents of tweets of geotagged and non-geotagged users. This empirical study addresses this limitation by applying text mining, statistical analysis, and machine learning techniques on Twitter data comprising more than 88,000 users and over 170 million tweets. Our findings show that there is a significant difference (p-value < 0.001) between geotagged and non-geotagged users based on 73% of the features obtained from the users’ profiles and tweets. The features can also help to distinguish between geotagged and non-geotagged users with around 80% accuracy. This research illustrates that geotagged users do not represent the Twitter population.
An Analysis of Existing Production Frameworks for Statistical and Geographic Information: Synergies, Gaps and Integration
Authors: Ariza-López Francisco Javier , Rodríguez-Pascual Antonio , Lopez-Pellicer Francisco J. , Vilches-Blázquez Luis M. , Villar-Iglesias Agustín , Masó Joan , Díaz-Díaz Efrén , Ureña-Cámara Manuel Antonio , González-Yanes Alberto
Published: June 2021

The production of official statistical and geospatial data is often in the hands of highly specialized public agencies that have traditionally followed their own paths and established their own production frameworks. In this article, we present the main frameworks of these two areas and focus on the possibility and need to achieve a better integration between them through the interoperability of systems, processes, and data. The statistical area is well led and has well-defined frameworks. The geospatial area does not have clear leadership and the large number of standards establish a framework that is not always obvious. On the other hand, the lack of a general and common legal framework is also highlighted. Additionally, three examples are offered: the first is the application of the spatial data quality model to the case of statistical data, the second of the application of the statistical process model to the geospatial case, and the third is the use of linked geospatial and statistical data. These examples demonstrate the possibility of transferring experiences/advances from one area to another. In this way, we emphasize the conceptual proximity of these two areas, highlighting synergies, gaps, and potential integration.
Perspectives on the Role of Magnetic Resonance Imaging (MRI) for Noninvasive Evaluation of Diabetic Kidney Disease
Authors: Mora-Gutiérrez José María , Fernández-Seara María A. , Echeverria-Chasco Rebeca , Garcia-Fernandez Nuria
Published: June 2021

Renal magnetic resonance imaging (MRI) techniques are currently in vogue, as they provide in vivo information on renal volume, function, metabolism, perfusion, oxygenation, and microstructural alterations, without the need for exogenous contrast media. New imaging biomarkers can be identified using these tools, which represent a major advance in the understanding and study of the different pathologies affecting the kidney. Diabetic kidney disease (DKD) is one of the most important diseases worldwide due to its high prevalence and impact on public health. However, its multifactorial etiology poses a challenge for both basic and clinical research. Therefore, the use of novel renal MRI techniques is an attractive step forward in the comprehension of DKD, both in its pathogenesis and in its detection and surveillance in the clinical practice. This review article outlines the most promising MRI techniques in the study of DKD, with the purpose of stimulating their clinical translation as possible tools for the diagnosis, follow-up, and monitoring of the clinical impacts of new DKD treatments.
Correlation between Potential Risk Factors and Pulmonary Embolism in Sarcoidosis Patients Timely Treated
Authors: Ruaro Barbara , Confalonieri Paola , Santagiuliana Mario , Wade Barbara , Baratella Elisa , Kodric Metka , Berria Maria , Jaber Mohamad , Torregiani Chiara , Bruni Cosimo , Confalonieri Marco , Salton Francesco
Published: June 2021

Background. Some studies with inconclusive results have reported a link between sarcoidosis and an increased risk of pulmonary embolism (PE). This study aimed at assessing a possible correlation between potential risk factors and PE in sarcoidosis patients. Methods. A total of 256 sarcoidosis patients (84 males and 172 females; mean age at diagnosis 49 ± 13) were enrolled after giving written informed consent. Clinical evaluations, laboratory and radiology tests were performed to evaluate the presence of pulmonary embolism. Results. Fifteen sarcoidosis patients with PE (4 males and 11 females; mean age at diagnosis 50 ± 11), diagnosed by lung scintigraphy and 241 sarcoidosis patients without PE (80 males and 161 females; mean age at diagnosis 47 ± 13), were observed. There was a statistically significant increase of the presence of antiphospholipid antibodies in the sarcoidosis group with pulmonary embolism. There was no statistically significant difference between the two groups as to smoking habit, obesity or hereditary thrombophilia frequency (p > 0.05, respectively). Conclusions. This study demonstrates a significant correlation between the presence of antiphospholipid antibody positivity and the pulmonary embolism events in our sarcoidosis patients. Furthermore, we propose screening for these antibodies and monitoring, aimed at timely treatment.
Human Nonmercaptalbumin Is a New Biomarker of Motor Function
Authors: Ito Sadayuki , Nakashima Hiroaki , Ando Kei , Kobayashi Kazuyoshi , Machino Masaaki , Seki Taisuke , Ishizuka Shinya , Kanbara Shunsuke , Inoue Taro , Koshimizu Hiroyuki , Fujii Ryosuke , Yamada Hiroya , Ando Yoshitaka , Ueyama Jun , Kondo Takaaki , Suzuki Koji , Hasegawa Yukiharu , Imagama Shiro
Published: June 2021

The ratio of human nonmercaptalbumin (HNA) and reduced albumin (HMA) may be a new marker for oxidative stress. Locomotive syndrome (LS) is reduced mobility due to impairment of locomotive organs. We investigated whether the HNA/HMA ratio could be a new biomarker of LS. This study included 306 subjects (mean age 64.24 ± 10.4 years) who underwent LS tests, grip strength, walking speed, and tests for HNA and HMA. Oxidative stress was measured by the ratio of HMA (f(HMA) = (HMA/(HMA + HNA) × 100)), and the subjects were divided into normal (N group; f[HMA] ≥ 70%) and low (L group; f[HMA] < 70%) groups. There were 124 non-elderly (<65 years) and 182 elderly subjects (≥65 years). There were no significant differences in LS, grip strength, and walking speed between the L and N groups in the non-elderly subjects. However, significant differences were found in the elderly subjects. In logistic regression analysis, there was an association between f(HMA) and the LS severity at older ages. LS in the elderly is associated with a decline in HMA and, thus, an increase in oxidative stress. Thus, f(HMA) is a new biomarker of LS.
Zinc Administration and Improved Serum Markers of Hepatic Fibrosis in Patients with Autoimmune Hepatitis
Authors: Moriya Kei , Nishimura Norihisa , Namisaki Tadashi , Takaya Hiroaki , Sawada Yasuhiko , Kawaratani Hideto , Kaji Kosuke , Shimozato Naotaka , Sato Shinya , Furukawa Masanori , Douhara Akitoshi , Akahane Takemi , Mitoro Akira , Yamao Junichi , Yoshiji Hitoshi
Published: June 2021

Aim: The aim of the present study is to investigate the effect of long-term zinc supplementation, which is important for the activation of various enzymes that contribute to antioxidant and antifibrotic activities, on the improvement of serum fibrotic markers in patients with autoimmune hepatitis (AIH). Methods: A total of 38 patients with AIH under regular treatment at our hospital who provided their consent for being treated with polaprezinc (75 mg twice daily) were included and classified into 2 groups: the patients with zinc elevation (n = 27) and the patients without zinc elevation (n = 11). Serum biomarker of fibrosis, protein expression levels of matrix metalloproteinases (MMPs), and their inhibitors (TIMPs) were evaluated. Results: A significant difference was found between the variability of serum procollagen type Ⅲ and collagen type Ⅳ-7S between the 2 groups before and after zinc administration for more than 24 months (p = 0.043 and p = 0.049). In the patients with zinc elevation, no significant changes were found in collagenase (MMP-1 and MMP-13) before and after zinc administration, whereas a significant increase in the expression of gelatinase (MMP-2 and MMP-9) was found after administration (p = 0.021 and p = 0.005). As for the relative ratio of MMPs to TIMPs, only MMP-9 to TIMP-1 showed a significant increase (p = 0.004). Conclusions: Long-term treatment with polaprezinc has been demonstrated to safely improve serum fibrosis indices through increases in MMP-2/-9 and MMP-9/TIMP-1 and is expected to be well combined with direct antifibrotic therapies such as molecularly targeted agents.
Probiotics, Prebiotics and Synbiotics in Inflammatory Bowel Diseases
Authors: Akutko Katarzyna , Stawarski Andrzej
Published: June 2021

Inflammatory bowel diseases (IBD), which include Crohn’s disease (CD) and ulcerative colitis (UC), are chronic inflammatory diseases of the digestive tract with periods of remission and relapses. The etiopathogenesis of IBD is multifactorial and has not been fully understood. Hence, only symptomatic treatment of these diseases is possible. The current pharmacological treatment has variable efficacy and is associated with the risk of significant side effects. Therefore, there is a constant need to search for new types of therapies with a high safety profile. Considering that the qualitative and quantitative profile of the gastrointestinal microbiome is often different in patients with IBD than in healthy individuals, there is a need for looking for therapies aimed at restoring intestinal microbiome homeostasis. Thus, the use of strictly defined probiotics, prebiotics and synbiotics may become an alternative form of IBD therapy. There is evidence that treatment with certain probiotic strains, e.g., VSL#3 and Escherischia coli Nissle 1917, is an effective form of therapy to induce remission in patients with mild to moderate UC. So far, the effectiveness of the use of probiotics, prebiotics and synbiotics in inducing or maintaining remission in patients with CD has not been confirmed. There are also reports of possible beneficial effects of fecal microbiota transplantation (FMT) on the course of IBD, especially UC. Further, well-planned studies on a large group of patients are needed to determine the role of specific probiotic strains, prebiotics, synbiotics and FMT in the treatment of IBD in adults and in children.
Molecular Fingerprints of Malignant Pleural Mesothelioma: Not Just a Matter of Genetic Alterations
Authors: Lorenzini Eugenia , Ciarrocchi Alessia , Torricelli Federica
Published: June 2021

Malignant pleural mesothelioma (MPM) is a clinical emergency of our time. Being strongly associated with asbestos exposure, incidence of this cancer is ramping up these days in many industrialized countries and it will soon start to increase in many developing areas where the use of this silicate derivate is still largely in use. Deficiency of reliable markers for the early identification of these tumors and the limited efficacy of the currently available therapeutic options are the basis of the impressive mortality rate of MPM. These shortcomings reflect the very poor information available about the molecular basis of this disease. Results of the recently released deep profiling studies point to the epigenome as a central element in MPM development and progression. First, MPM is characterized by a low mutational burden and a highly peculiar set of mutations that hits almost exclusively epigenetic keepers or proteins controlling chromatin organization and function. Furthermore, asbestos does not seem to be associated with a distinctive mutational signature, while the precise mapping of epigenetic changes caused by this carcinogen has been defined, suggesting that alterations in epigenetic features are the driving force in the development of this disease. Last but not least, consistent evidence also indicates that, in the setting of MPM, chromatin rewiring and epigenetic alterations of cancer cells heavily condition the microenvironment, including the immune response. In this review we aim to point to the relevance of the epigenome in MPM and to highlight the dependency of this tumor on chromatin organization and function. We also intend to discuss the opportunity of targeting these mechanisms as potential therapeutic options for MPM.
Association of Frailty with Adverse Outcomes in Patients with Suspected COVID-19 Infection
Authors: Simon Noemi R. , Jauslin Andrea S. , Rueegg Marco , Twerenbold Raphael , Lampart Maurin , Osswald Stefan , Bassetti Stefano , Tschudin-Sutter Sarah , Siegemund Martin , Nickel Christian H. , Bingisser Roland
Published: June 2021

Older age and frailty are predictors of adverse outcomes in patients with COVID-19. In emergency medicine, patients do not present with the diagnosis, but with suspicion of COVID-19. The aim of this study was to assess the association of frailty and age with death or admission to intensive care in patients with suspected COVID-19. This single-centre prospective cohort study was performed in the Emergency Department of a tertiary care hospital. Patients, 65 years and older, with suspected COVID-19 presenting to the Emergency Department during the first wave of the pandemic were consecutively enrolled. All patients underwent nasopharyngeal SARS-CoV-2 PCR swab tests. Patients with a Clinical Frailty Scale (CFS) > 4, were considered to be frail. Associations between age, gender, frailty, and COVID-19 status with the composite adverse outcome of 30-day-intensive-care-admission and/or 30-day-mortality were tested. In the 372 patients analysed, the median age was 77 years, 154 (41.4%) were women, 44 (11.8%) were COVID-19-positive, and 125 (33.6%) were frail. The worst outcome was seen in frail COVID-19-patients with six (66.7%) adverse outcomes. Frailty (CFS > 4) and COVID-19-positivity were associated with an adverse outcome after adjustment for age and gender (frailty: OR 5.01, CI 2.56–10.17, p < 0.001; COVID-19: OR 3.47, CI 1.48–7.89, p = 0.003). Frailty was strongly associated with adverse outcomes and outperformed age as a predictor in emergency patients with suspected COVID-19.
The Role of Premorbid IQ and Age of Onset as Useful Predictors of Clinical, Functional Outcomes, and Recovery of Individuals with a First Episode of Psychosis
Authors: Molina-García Mariola , Fraguas David , del Rey-Mejías Ángel , Mezquida Gisela , Sánchez-Torres Ana M. , Amoretti Silvia , Lobo Antonio , González-Pinto Ana , Andreu-Bernabeu Álvaro , Corripio Iluminada , Vieta Eduard , Baeza Inmaculada , Mané Anna , Cuesta Manuel , de la Serna Elena , Payá Beatriz , Zorrilla Iñaki , Arango Celso , Bernardo Miquel , Rapado-Castro Marta , Parellada Mara
Published: June 2021

Background: premorbid IQ (pIQ) and age of onset are predictors of clinical severity and long-term functioning after a first episode of psychosis. However, the additive influence of these variables on clinical, functional, and recovery rates outcomes is largely unknown. Methods: we characterized 255 individuals who have experienced a first episode of psychosis in four a priori defined subgroups based on pIQ (low pIQ < 85; average pIQ ≥ 85) and age of onset (early onset < 18 years; adult onset ≥ 18 years). We conducted clinical and functional assessments at baseline and at two-year follow-up. We calculated symptom remission and recovery rates using the Positive and Negative Symptoms of Schizophrenia Schedule (PANSS) and the Global Assessment Functioning (GAF or Children-GAF). We examined clinical and functional changes with pair-wise comparisons and two-way mixed ANOVA. We built hierarchical lineal and logistic regression models to estimate the predictive value of the independent variables over functioning or recovery rates. Results: early-onset patients had more severe positive symptoms and poorer functioning than adult-onset patients. At two-year follow-up, only early-onset with low pIQ and adult-onset with average pIQ subgroups differed consistently, with the former having more negative symptoms (d = 0.59), poorer functioning (d = 0.82), lower remission (61% vs. 81.1%), and clinical recovery (34.1% vs. 62.2%). Conclusions: early-onset individuals with low pIQ may present persistent negative symptoms, lower functioning, and less recovery likelihood at two-year follow-up. Intensive cognitive and functional programs for these individuals merit testing to improve long-term recovery rates in this subgroup.
Atrial and Ventricular Structural and Functional Alterations in Obese Children
Authors: Šileikienė Rima , Adamonytė Karolina , Ziutelienė Aristida , Ramanauskienė Eglė , Vaškelytė Jolanta Justina
Published: June 2021

Background and objectives: Childhood obesity has reached epidemic levels in the world. Obesity in children is defined as a body mass index (BMI) equal to or above the 95th percentile for age and sex. The aim of this study was to determine early changes in cardiac structure and function in obese children by comparing them with their nonobese peers, using echocardiography methods. Materials and methods: The study enrolled 35 obese and 37 age-matched nonobese children. Standardized 2-dimensional (2D), pulsed wave tissue Doppler, and 2D speckle tracking echocardiography were performed. The z-score BMI and lipid metabolism were assessed in all children. Results: Obese children (aged 13.51 ± 2.15 years; 20 boys; BMI z-score of 0.88 ± 0.63) were characterized by enlarged ventricular and atrial volumes, a thicker left ventricular posterior wall, and increased left ventricular mass. Decreased LV and RV systolic and diastolic function was found in obese children. Atrial peak negative (contraction) strain (−2.05% ± 2.17% vs. −4.87% ± 2.97%, p < 0.001), LV and RV global longitudinal strain (−13.3% ± 2.88% vs. −16.87% ± 3.39%; −12.51% ± 10.09% vs. −21.51% ± 7.42%, p < 0.001), and LV global circumferential strain (−17.0 ± 2.7% vs. −19.5 ± 2.9%, p < 0.001) were reduced in obese children. LV torsion (17.94° ± 2.07° vs. 12.45° ± 3.94°, p < 0.001) and normalized torsion (2.49 ± 0.4°/cm vs. 1.86 ± 0.61°/cm, p = 0.001) were greater in obese than nonobese children. A significant inverse correlation was found between LV and RV global longitudinal strain and BMI (r = −0.526, p < 0.01; r = −0.434, p < 0.01) and total cholesterol (r = −0.417, p < 0.01). Multivariate analysis revealed that the BMI z-score was independently related to LV and RV global longitudinal strain as well as LV circumferential and radial strain. Conclusion: 2D speckle tracking echocardiography is beneficial in the early detection of regional LV systolic and diastolic dysfunctions, with preserved ejection fraction as well as additional RV and atrial involvement, in obese children. Obesity may negatively influence atrial and ventricular function, as measured by 2D speckle tracking echocardiography. Obese children, though they are apparently healthy, may have subclinical myocardial dysfunction.
β-Thujaplicin Enhances TRAIL-Induced Apoptosis via the Dual Effects of XIAP Inhibition and Degradation in NCI-H460 Human Lung Cancer Cells
Authors: Seno Saki , Kimura Minori , Yashiro Yuki , Kimura Ryutaro , Adachi Kanae , Terabayashi Aoi , Takahashi Mio , Oyama Takahiro , Abe Hideaki , Abe Takehiko , Tanuma Sei-ichi , Takasawa Ryoko
Published: June 2021

Background: β-thujaplicin, a natural tropolone derivative, has anticancer effects on various cancer cells via apoptosis. However, the apoptosis regulatory proteins involved in this process have yet to be revealed. Methods: Trypan blue staining, a WST-8 assay, and a caspase-3/7 activity assay were used to investigate whether β-thujaplicin sensitizes cancer cells to TNF-related apoptosis-inducing ligand (TRAIL)-mediated apoptosis. Additionally, western blotting was performed to clarify the effects of β-thujaplicin on X-linked inhibitor of apoptosis protein (XIAP) in NCI-H460 cells and a fluorescence polarization binding assay was used to evaluate the binding-inhibitory activity of β-thujaplicin against XIAP-BIR3. Results: β- and γ-thujaplicins decreased the viability of NCI-H460 cells in a dose-dependent manner; they also sensitized the cells to TRAIL-induced cell growth inhibition and apoptosis. β-thujaplicin significantly potentiated the apoptosis induction effect of TRAIL on NCI-H460 cells, which was accompanied by enhanced caspase-3/7 activity. Interestingly, β-thujaplicin treatment in NCI-H460 cells decreased XIAP levels. Furthermore, β-thujaplicin was able to bind XIAP-BIR3 at the Smac binding site. Conclusions: These findings indicate that β-thujaplicin could enhance TRAIL-induced apoptosis in NCI-H460 cells via XIAP inhibition and degradation. Thus, the tropolone scaffold may be useful for designing novel nonpeptidic small-molecule inhibitors of XIAP and developing new types of anticancer drugs.
Hepatocrinology
Authors: Kalra Sanjay , Bhattacharya Saptarshi , Rawal Pawan
Published: June 2021

Hepatocrinology is defined as a bidirectional, complex relationship between hepatic physiology and endocrine function, hepatic disease and endocrine dysfunction, hepatotropic drugs and endocrine function, and endocrine drugs and hepatic health. The scope of hepatocrinology includes conditions of varied etiology (metabolic, infectious, autoimmune, and invasive) that we term as hepato-endocrine syndromes. This perspective shares the definition, concept, and scope of hepatocrinology and shares insight related to this aspect of medicine. It is hoped that this communication will encourage further attention and research in this critical field.
Plasma Metabolites, Productive Performance and Rumen Volatile Fatty Acid Profiles of Northern Australian Bos indicus Steers Supplemented with Desmanthus and Lucerne
Authors: Suybeng Bénédicte , Charmley Edward , Gardiner Christopher P. , Malau-Aduli Bunmi S. , Malau-Aduli Aduli E. O.
Published: June 2021

The hypothesis tested was that tropical steers supplemented with the Desmanthus legume and lucerne, a widely characterized temperate legume of high nutritive value, would elicit similar responses in plasma metabolite profiles, productive performance, nitrogen retention, and volatile fatty acids (VFA). The tannin-binding compound, polyethylene glycol-4000 (PEG), was added to the diets (160 g/kg Desmanthus dry matter) with the objective of further exploring nitrogen (N) utilization in the animals supplemented with Desmanthus relative to lucerne. From February to June 2020, sixteen yearling Brangus steers (average liveweight of 232 ± 6 kg) were fed a background diet of Rhodes grass (Chloris gayana) hay for 28 days, before introducing three Desmanthus cultivars (Desmanthus virgatus cv. JCU2, D. bicornutus cv. JCU4, D. leptophyllus cv. JCU7) and lucerne (Medicago sativa) at 30% dry matter intake (DMI). Relative to the backgrounding period, all supplemented steers exhibited similar growth performance. Steers supplemented with Desmanthus recorded a lower DMI and animal growth performance, but higher fecal N concentration than animals supplemented with lucerne. Among the three Desmanthus cultivars, there were no significant differences in N concentrations, VFA, and plasma metabolite profiles. The addition of PEG induced higher rumen iso-acid concentrations and fecal N excretion. However, feeding Desmanthus spp. to tropical Bos indicus steers could be a valuable means of increasing N utilization, which is attributable to the presence of tannins, and, consequently, improve animal productive performance. Since supplementation with lucerne resulted in higher liveweight, daily liveweight gains, and overall animal performance than supplementing with Desmanthus, the tested hypothesis that both supplements will elicit similar animal performance does not hold and must be rejected. Further in vivo investigation is needed to better understand the impact of tannins in Desmanthus on N utilization.
Saffron Pre-Treatment Promotes Reduction in Tissue Inflammatory Profiles and Alters Microbiome Composition in Experimental Colitis Mice
Authors: Banskota Suhrid , Brim Hassan , Kwon Yun Han , Singh Gulshan , Sinha Sidhartha R. , Wang Huaqing , Khan Waliul I. , Ashktorab Hassan
Published: June 2021

Inflammatory bowel disease (IBD) is a chronic inflammatory condition of the gastrointestinal tract with an incompletely understood pathogenesis. Long-standing colitis is associated with increased risk of colon cancer. Despite the availability of various anti-inflammatory and immunomodulatory drugs, many patients fail to respond to pharmacologic therapy and some experience drug-induced adverse events. Dietary supplements, particularly saffron (Crocus sativus), have recently gained an appreciable attention in alleviating some symptoms of digestive diseases. In our study, we investigated whether saffron may have a prophylactic effect in a murine colitis model. Saffron pre-treatment improved the gross and histopathological characteristics of the colonic mucosa in murine experimental colitis. Treatment with saffron showed a significant amelioration of colitis when compared to the vehicle-treated mice group. Saffron treatment significantly decreased secretion of serotonin and pro-inflammatory cytokines, such as TNF-α, IL-1β, and IL-6, in the colon tissues by suppressing the nuclear translocation of NF-κB. The gut microbiome analysis revealed distinct clusters in the saffron-treated and untreated mice in dextran sulfate sodium (DSS)-induced colitis by visualization of the Bray–Curtis diversity by principal coordinates analysis (PCoA). Furthermore, we observed that, at the operational taxonomic unit (OTU) level, Cyanobacteria were depleted, while short-chain fatty acids (SCFAs), such as isobutyric acid, acetic acid, and propionic acid, were increased in saffron-treated mice. Our data suggest that pre-treatment with saffron inhibits DSS-induced pro-inflammatory cytokine secretion, modulates gut microbiota composition, prevents the depletion of SCFAs, and reduces the susceptibility to colitis.
Soft, Formstable (Co)Polyester Blend Elastomers
Authors: Neffe Axel , Izraylit Victor , Hommes-Schattmann Paul , Lendlein Andreas
Published: June 2021

High crystallization rate and thermomechanical stability make polylactide stereocomplexes effective nanosized physical netpoints. Here, we address the need for soft, form-stable degradable elastomers for medical applications by designing such blends from (co)polyesters, whose mechanical properties are ruled by their nanodimensional architecture and which are applied as single components in implants. By careful controlling of the copolymer composition and sequence structure of poly[(L-lactide)-co-(ε-caprolactone)], it is possible to prepare hyperelastic polymer blends formed through stereocomplexation by adding poly(D-lactide) (PDLA). Low glass transition temperature Tg ≤ 0 °C of the mixed amorphous phase contributes to the low Young’s modulus E. The formation of stereocomplexes is shown in DSC by melting transitions Tm > 190 °C and in WAXS by distinct scattering maxima at 2θ = 12° and 21°. Tensile testing demonstrated that the blends are soft (E = 12–80 MPa) and show an excellent hyperelastic recovery Rrec = 66–85% while having high elongation at break εb up to >1000%. These properties of the blends are attained only when the copolymer has 56–62 wt% lactide content, a weight average molar mass >140 kg·mol−1, and number average lactide sequence length ≥4.8, while the blend is formed with a content of 5–10 wt% of PDLA. The devised strategy to identify a suitable copolymer for stereocomplexation and blend formation is transferable to further polymer systems and will support the development of thermoplastic elastomers suitable for medical applications.
Hedgehogs and Squirrels as Hosts of Zoonotic Bartonella Species
Authors: Majerová Karolina , Gutiérrez Ricardo , Fonville Manoj , Hönig Václav , Papežík Petr , Hofmannová Lada , Lesiczka Paulina Maria , Nachum-Biala Yaarit , Růžek Daniel , Sprong Hein , Harrus Shimon , Modrý David , Votýpka Jan
Published: June 2021

Free-living animals frequently play a key role in the circulation of various zoonotic vector-borne pathogens. Bacteria of the genus Bartonella are transmitted by blood-feeding arthropods and infect a large range of mammals. Although only several species have been identified as causative agents of human disease, it has been proposed that any Bartonella species found in animals may be capable of infecting humans. Within a wide-ranging survey in various geographical regions of the Czech Republic, cadavers of accidentally killed synurbic mammalian species, namely Eurasian red squirrel (Sciurus vulgaris), European hedgehog (Erinaceus europaeus) and Northern white-breasted hedgehog (Erinaceus roumanicus), were sampled and tested for Bartonella presence using multiple PCR reaction approach targeting several DNA loci. We demonstrate that cadavers constitute an available and highly useful source of biological material for pathogen screening. High infection rates of Bartonella spp., ranging from 24% to 76%, were confirmed for all three tested mammalian species, and spleen, ear, lung and liver tissues were demonstrated as the most suitable for Bartonella DNA detection. The wide spectrum of Bartonella spp. that were identified includes three species with previously validated zoonotic potential, B. grahamii, B. melophagi and B. washoensis, accompanied by ‘Candidatus B. rudakovii’ and two putative novel species, Bartonella sp. ERIN and Bartonella sp. SCIER.