bluuebunny/crossref_metadata_2025 huggingface dataset:
Food Environment Typology: Advancing an Expanded Definition, Framework, and Methodological Approach for Improved Characterization of Wild, Cultivated, and Built Food Environments toward Sustainable Diets
Authors: Downs Shauna M. , Ahmed Selena , Fanzo Jessica , Herforth Anna
Published: April 2020

The food environment is a critical place in the food system to implement interventions to support sustainable diets and address the global syndemic of obesity, undernutrition, and climate change, because it contains the total scope of options within which consumers make decisions about which foods to acquire and consume. In this paper, we build on existing definitions of the food environment, and provide an expanded definition that includes the parameter of sustainability properties of foods and beverages, in order to integrate linkages between food environments and sustainable diets. We further provide a graphical representation of the food environment using a socio-ecological framework. Next, we provide a typology with descriptions of the different types of food environments that consumers have access to in low-, middle-, and high-income countries including wild, cultivated, and built food environments. We characterize the availability, affordability, convenience, promotion and quality (previously termed desirability), and sustainability properties of food and beverages for each food environment type. Lastly, we identify a methodological approach with potential objective and subjective tools and metrics for measuring the different properties of various types of food environments. The definition, framework, typology, and methodological toolbox presented here are intended to facilitate scholars and practitioners to identify entry points in the food environment for implementing and evaluating interventions that support sustainable diets for enhancing human and planetary health.
Analyzing Lung Disease Using Highly Effective Deep Learning Techniques
Authors: Sriporn Krit , Tsai Cheng-Fa , Tsai Chia-En , Wang Paohsi
Published: April 2020

Image processing technologies and computer-aided diagnosis are medical technologies used to support decision-making processes of radiologists and medical professionals who provide treatment for lung disease. These methods involve using chest X-ray images to diagnose and detect lung lesions, but sometimes there are abnormal cases that take some time to occur. This experiment used 5810 images for training and validation with the MobileNet, Densenet-121 and Resnet-50 models, which are popular networks used to classify the accuracy of images, and utilized a rotational technique to adjust the lung disease dataset to support learning with these convolutional neural network models. The results of the convolutional neural network model evaluation showed that Densenet-121, with a state-of-the-art Mish activation function and Nadam-optimized performance. All the rates for accuracy, recall, precision and F1 measures totaled 98.88%. We then used this model to test 10% of the total images from the non-dataset training and validation. The accuracy rate was 98.97% for the result which provided significant components for the development of a computer-aided diagnosis system to yield the best performance for the detection of lung lesions.
Sleep and Wellbeing, Now and in the Future
Authors: Chow Chin Moi
Published: April 2020

The processes of sleeping, eating and moving, in concert with cognition and learning, support health and life [...]
Multiple Stressor Effects of Radon and Phthalates in Children: Background Information and Future Research
Authors: Kwan W. S. , Nikezic D. , Roy Vellaisamy A. L. , Yu K. N.
Published: April 2020

The present paper reviews available background information for studying multiple stressor effects of radon (222Rn) and phthalates in children and provides insights on future directions. In realistic situations, living organisms are collectively subjected to many environmental stressors, with the resultant effects being referred to as multiple stressor effects. Radon is a naturally occurring radioactive gas that can lead to lung cancers. On the other hand, phthalates are semi-volatile organic compounds widely applied as plasticizers to provide flexibility to plastic in consumer products. Links of phthalates to various health effects have been reported, including allergy and asthma. In the present review, the focus on indoor contaminants was due to their higher concentrations and to the higher indoor occupancy factor, while the focus on the pediatric population was due to their inherent sensitivity and their spending more time close to the floor. Two main future directions in studying multiple stressor effects of radon and phthalates in children were proposed. The first one was on computational modeling and micro-dosimetric studies, and the second one was on biological studies. In particular, dose-response relationship and effect-specific models for combined exposures to radon and phthalates would be necessary. The ideas and methodology behind such proposed research work are also applicable to studies on multiple stressor effects of collective exposures to other significant airborne contaminants, and to population groups other than children.
Chemokine Ligand 13 (CXCL13) in Neuroborreliosis and Neurosyphilis as Selected Spirochetal Neurological Diseases: A Review of Its Diagnostic Significance
Authors: Gudowska-Sawczuk Monika , Mroczko Barbara
Published: April 2020

Neuroborreliosis (NB) and neurosyphilis (NS) are abnormal conditions caused by spirochetal bacteria which affect the nervous system. Diagnosis of neuroborreliosis and neurosyphilis is determined by clinical examination of visible symptoms, serum and cerebrospinal fluid (CSF) analysis, and serological detection of antibodies against Borrelia burgdorferi sensu lato and Treponema pallidum, respectively. Establishing a diagnosis may sometimes pose a number of diagnostic difficulties. A potential role of chemokine ligand 13 (CXCL13) as an accurate diagnostic biomarker of intrathecal inflammation has been suggested. In this review, we focused on changes in serum and cerebrospinal fluid concentration of chemokine ligand 13 in selected spirochetal neurological diseases neuroborreliosis and neurosyphilis reported in the available literature. We performed an extensive search of the literature relevant to our investigation via the MEDLINE/PubMed database. It has been proven that CXCL13 determination can provide rapid information regarding central nervous system inflammation in patients with selected spirochetosis. We described that neuroborreliosis and neurosyphilis are associated with an elevated CXCL13 concentration, mainly in the cerebrospinal fluid. Moreover, literature data suggest that CXCL13 determination is the most interesting additional marker for diagnosis and monitoring of neuroborreliosis and neurosyphilis thanks to its high sensitivity. Based on these published findings, we suggest that CXCL13 has high diagnostic utility and may be applied in laboratory diagnostics as a potential diagnostic marker in human spirochetal neurologic diseases.
Non-Starch Polysaccharides in Durum Wheat: A Review
Authors: Marcotuli Ilaria , Colasuonno Pasqualina , Hsieh Yves S. Y. , Fincher Geoffrey B. , Gadaleta Agata
Published: April 2020

Durum wheat is one of most important cereal crops that serves as a staple dietary component for humans and domestic animals. It provides antioxidants, proteins, minerals and dietary fibre, which have beneficial properties for humans, especially as related to the health of gut microbiota. Dietary fibre is defined as carbohydrate polymers that are non-digestible in the small intestine. However, this dietary component can be digested by microorganisms in the large intestine and imparts physiological benefits at daily intake levels of 30–35 g. Dietary fibre in cereal grains largely comprises cell wall polymers and includes insoluble (cellulose, part of the hemicellulose component and lignin) and soluble (arabinoxylans and (1,3;1,4)-β-glucans) fibre. More specifically, certain components provide immunomodulatory and cholesterol lowering activity, faecal bulking effects, enhanced absorption of certain minerals, prebiotic effects and, through these effects, reduce the risk of type II diabetes, cardiovascular disease and colorectal cancer. Thus, dietary fibre is attracting increasing interest from cereal processors, producers and consumers. Compared with other components of the durum wheat grain, fibre components have not been studied extensively. Here, we have summarised the current status of knowledge on the genetic control of arabinoxylan and (1,3;1,4)-β-glucan synthesis and accumulation in durum wheat grain. Indeed, the recent results obtained in durum wheat open the way for the improvement of these important cereal quality parameters.
Hemokinin-1 Gene Expression Is Upregulated in Trigeminal Ganglia in an Inflammatory Orofacial Pain Model: Potential Role in Peripheral Sensitization
Authors: Aczél Timea , Kecskés Angéla , Kun József , Szenthe Kálmán , Bánáti Ferenc , Szathmary Susan , Herczeg Róbert , Urbán Péter , Gyenesei Attila , Gaszner Balázs , Helyes Zsuzsanna , Bölcskei Kata
Published: April 2020

A large percentage of primary sensory neurons in the trigeminal ganglia (TG) contain neuropeptides such as tachykinins or calcitonin gene-related peptide. Neuropeptides released from the central terminals of primary afferents sensitize the secondary nociceptive neurons in the trigeminal nucleus caudalis (TNC), but also activate glial cells contributing to neuroinflammation and consequent sensitization in chronic orofacial pain and migraine. In the present study, we investigated the newest member of the tachykinin family, hemokinin-1 (HK-1) encoded by the Tac4 gene in the trigeminal system. HK-1 had been shown to participate in inflammation and hyperalgesia in various models, but its role has not been investigated in orofacial pain or headache. In the complete Freund’s adjuvant (CFA)-induced inflammatory orofacial pain model, we showed that Tac4 expression increased in the TG in response to inflammation. Duration-dependent Tac4 upregulation was associated with the extent of the facial allodynia. Tac4 was detected in both TG neurons and satellite glial cells (SGC) by the ultrasensitive RNAscope in situ hybridization. We also compared gene expression changes of selected neuronal and glial sensitization and neuroinflammation markers between wild-type and Tac4-deficient (Tac4-/-) mice. Expression of the SGC/astrocyte marker in the TG and TNC was significantly lower in intact and saline/CFA-treated Tac4-/- mice. The procedural stress-related increase of the SGC/astrocyte marker was also strongly attenuated in Tac4-/- mice. Analysis of TG samples with a mouse neuroinflammation panel of 770 genes revealed that regulation of microglia and cytotoxic cell-related genes were significantly different in saline-treated Tac4-/- mice compared to their wild-types. It is concluded that HK-1 may participate in neuron-glia interactions both under physiological and inflammatory conditions and mediate pain in the trigeminal system.
The Separation and Characterization of Extracellular Vesicles from Medium Conditioned by Bovine Embryos
Authors: Pavani Krishna Chaitanya , Lin Xiaoyuan , Hamacher Joachim , Broeck Wim Van Den , Couck Liesbeth , Peelman Luc , Hendrix An , Van Soom Ann
Published: April 2020

Extracellular vesicles (EVs) have been identified as one of the communication mechanisms amongst embryos. They are secreted into the embryo culture medium and, as such, represent a source of novel biomarkers for identifying the quality of cells and embryos. However, only small amounts of embryo-conditioned medium are available, which represents a challenge for EV enrichment. Our aim is to assess the suitability of different EV separation methods to retrieve EVs with high specificity and sufficient efficiency. Bovine embryo-conditioned medium was subjected to differential ultracentrifugation (DU), OptiPrepTM density gradient (ODG) centrifugation, and size exclusion chromatography. Separated EVs were characterized by complementary characterization methods, including Western blot, electron microscopy, and nanoparticle tracking analysis, to assess the efficiency and specificity. OptiPrepTM density gradient centrifugation outperformed DU and SEC in terms of specificity by substantial removal of contaminating proteins such as ribonucleoprotein complexes (Argonaute-2 (AGO-2)) and lipoproteins (ApoA-I) from bovine embryo-derived EVs (density: 1.02–1.04, 1.20–1.23 g/mL, respectively). In conclusion, ODG centrifugation is the preferred method for identifying EV-enriched components and for improving our understanding of EV function in embryo quality and development.
PACAP Modulates the Autophagy Process in an In Vitro Model of Amyotrophic Lateral Sclerosis
Authors: D’Amico Agata Grazia , Maugeri Grazia , Saccone Salvatore , Federico Concetta , Cavallaro Sebastiano , Reglodi Dora , D’Agata Velia
Published: April 2020

Amyotrophic lateral sclerosis (ALS) is a progressive neurodegenerative disease of complex etiology leading to motor neuron degeneration. Many gene alterations cause this pathology, including mutation in Cu, Zn superoxide dismutase (SOD1), which leads to its gain of function. Mutant SOD1 proteins are prone to aberrant misfolding and create aggregates that impair autophagy. The hypoxic stress is strictly linked to the disease progression since it induces uncontrolled autophagy activation and the consequent high rates of cell death. Previously, we showed that pituitary adenylate cyclase-activating polypeptide (PACAP) exerts neurotrophic activity in cultured mSOD1 motor neurons exposed to serum deprivation. To date, no studies have examined whether the protective effect of PACAP on mSOD1 cells exposed to hypoxic insult is mediated through the regulation of the autophagy process. In the present study, we used the neuroblastoma-spinal cord-34 (NSC-34) cell line, stably expressing human wild type or mutant SOD1 G93A, to represent a well characterized in vitro model of a familial form of ALS. These cells were exposed to 100-µM desferrioxamine mesylate salt for 24h, to mimic the hypoxic stress affecting motor neurons during the disease progression. Our results showed that PACAP treatment significantly reduced cell death and hypoxia-induced mSOD1 accumulation by modulating the autophagy process in G93A motor neurons, as revealed by the decreased LC3II and the increased p62 levels, two autophagy indicators. These results were also confirmed by evaluating the vacuole formation detected through light chain 3 (LC3) immunofluorescence. Furthermore, the PACAP effects on autophagy seem to be mediated through the activation of the MAPK/ERK signaling pathway. Overall, our data demonstrated that PACAP exerts an ameliorative effect on the mSOD1 motor neuron viability by modulating a hypoxia-induced autophagy process through activation of MAPK/ERK signaling cascade.
Sex-Specific SARS-CoV-2 Mortality: Among Hormone-Modulated ACE2 Expression, Risk of Venous Thromboembolism and Hypovitaminosis D
Authors: La Vignera Sandro , Cannarella Rossella , Condorelli Rosita A. , Torre Francesco , Aversa Antonio , Calogero Aldo E.
Published: April 2020

Severe acute respiratory syndrome coronavirus (SARS-CoV-2) disease (COVID-19) appears to have a higher mortality rate in presence of comorbidities and in men. The latter suggests the presence of a possible sex-dependent susceptibility. An enzymatic system involved in this different predisposition could be represented by angiotensin converting enzyme 2 (ACE2). ACE2 is activated and down-regulated by the spike protein of the virus and allows the penetration of SARS-CoV-2 into epithelial cells and myocardium. Data on the experimental animal have shown that 17ß-estradiol increases the expression and activity of ACE2 in both adipose tissue and kidney. Spontaneously hypertensive male mice have a higher myocardial ACE2 expression than females and its levels decrease after orchiectomy. In addition to this first aspect, the recent evidence of an increased frequency of venous thromboembolism in patients with COVID-19 (a clinical element associated with a worse prognosis) calls the attention on the safety of treatment with testosterone, in particular in hypogonadal men with greater genetic predisposition. Evidence that sex hormones are able to modulate the expression of ACE2 could help in interpreting epidemiological results and in designing more appropriate intervention strategies. Moreover, the vitamin D deficiency in elderly men may be worthy of further study regarding the epidemiological aspects of this different susceptibility and lethality between sexes.
Kisspeptin and Testicular Function—Is It Necessary?
Authors: Sharma Aditi , Thaventhiran Thilipan , Minhas Suks , Dhillo Waljit S. , Jayasena Channa N.
Published: April 2020

The role of kisspeptin in stimulating hypothalamic GnRH is undisputed. However, the role of kisspeptin signaling in testicular function is less clear. The testes are essential for male reproduction through their functions of spermatogenesis and steroidogenesis. Our review focused on the current literature investigating the distribution, regulation and effects of kisspeptin and its receptor (KISS1/KISS1R) within the testes of species studied to date. There is substantial evidence of localised KISS1/KISS1R expression and peptide distribution in the testes. However, variability is observed in the testicular cell types expressing KISS1/KISS1R. Evidence is presented for modulation of steroidogenesis and sperm function by kisspeptin signaling. However, the physiological importance of such effects, and whether these are paracrine or endocrine manifestations, remain unclear.
Deeping in the Role of the MAP-Kinases Interacting Kinases (MNKs) in Cancer
Authors: Pinto-Díez Celia , Ferreras-Martín Raquel , Carrión-Marchante Rebeca , González Víctor M. , Martín María Elena
Published: April 2020

The mitogen-activated protein kinase (MAPK)-interacting kinases (MNKs) are involved in oncogenic transformation and can promote metastasis and tumor progression. In human cells, there are four MNKs isoforms (MNK1a/b and MNK2a/b), derived from two genes by alternative splicing. These kinases play an important role controlling the expression of specific proteins involved in cell cycle, cell survival and cell motility via eukaryotic initiation factor 4E (eIF4E) regulation, but also through other substrates such as heterogeneous nuclear ribonucleoprotein A1, polypyrimidine tract-binding protein-associated splicing factor and Sprouty 2. In this review, we provide an overview of the role of MNK in human cancers, describing the studies conducted to date to elucidate the mechanism involved in the action of MNKs, as well as the development of MNK inhibitors in different hematological cancers and solid tumors.
Overcoming Intrinsic Doxorubicin Resistance in Melanoma by Anti-Angiogenic and Anti-Metastatic Effects of Liposomal Prednisolone Phosphate on Tumor Microenvironment
Authors: Licarete Emilia , Rauca Valentin Florian , Luput Lavinia , Drotar Denise , Stejerean Ioana , Patras Laura , Dume Bogdan , Toma Vlad Alexandru , Porfire Alina , Gherman Claudia , Sesarman Alina , Banciu Manuela
Published: April 2020

Regardless of recent progress, melanoma is very difficult to treat, mainly due to the drug resistance modulated by tumor cells as well as by the tumor microenvironment (TME). Among the immune cells recruited at the tumor site, tumor associated macrophages (TAMs) are the most abundant, promoting important tumorigenic processes: angiogenesis, inflammation and invasiveness. Furthermore, it has been shown that TAMs are involved in mediating the drug resistance of melanoma cells. Thus, in the present study, we used liposomal formulation of prednisolone disodium phosphate (LCL-PLP) to inhibit the protumor function of TAMs with the aim to sensitize the melanoma cells to the cytotoxic drug doxorubicin (DOX) to which human melanoma has intrinsic resistance. Consequently, we evaluated the in vivo effects of the concomitant administration of LCL-PLP and liposomal formulation of DOX (LCL-DOX) on B16.F10 melanoma growth and on the production of key molecular markers for tumor development. Our results demonstrated that the concomitant administration of LCL-PLP and LCL-DOX induced a strong inhibition of tumor growth, primarily by inhibiting TAMs-mediated angiogenesis as well as the tumor production of MMP-2 and AP-1. Moreover, our data suggested that the combined therapy also affected TME as the number of infiltrated macrophages in melanoma microenvironment was reduced significantly.
SGLT2 Inhibitor Empagliflozin and DPP4 Inhibitor Linagliptin Reactivate Glomerular Autophagy in db/db Mice, a Model of Type 2 Diabetes
Authors: Korbut Anton I. , Taskaeva Iuliia S. , Bgatova Nataliya P. , Muraleva Natalia A. , Orlov Nikolai B. , Dashkin Maksim V. , Khotskina Anna S. , Zavyalov Evgenii L. , Konenkov Vladimir I. , Klein Thomas , Klimontov Vadim V.
Published: April 2020

Recent data have indicated the emerging role of glomerular autophagy in diabetic kidney disease. We aimed to assess the effect of the SGLT2 inhibitor empagliflozin, the DPP4 inhibitor linagliptin, and their combination, on glomerular autophagy in a model of type 2 diabetes. Eight-week-old male db/db mice were randomly assigned to treatment with empagliflozin, linagliptin, empagliflozin–linagliptin or vehicle for 8 weeks. Age-matched non-diabetic db/+ mice acted as controls. To estimate glomerular autophagy, immunohistochemistry for beclin-1 and LAMP-1 was performed. Podocyte autophagy was assessed by counting the volume density (Vv) of autophagosomes, lysosomes and autolysosomes by transmission electron microscopy. LC3B and LAMP-1, autophagy markers, and caspase-3 and Bcl-2, apoptotic markers, were evaluated in renal cortex by western blot. Vehicle-treated db/db mice had weak glomerular staining for beclin-1 and LAMP-1 and reduced Vv of autophagosomes, autolysosomes and lysosomes in podocytes. Empagliflozin and linagliptin, both as monotherapy and in combination, enhanced the areas of glomerular staining for beclin-1 and LAMP-1 and increased Vv of autophagosomes and autolysosomes in podocytes. Renal LC3B and Bcl-2 were restored in actively treated animals. LAMP-1 expression was enhanced in the empagliflozin group; caspase-3 expression decreased in the empagliflozin–linagliptin group only. Mesangial expansion, podocyte foot process effacement and urinary albumin excretion were mitigated by both agents. The data provide further explanation for the mechanism of the renoprotective effect of SGLT2 inhibitors and DPP4 inhibitors in diabetes.
A Novel CD147 Inhibitor, SP-8356, Attenuates Pathological Fibrosis in Alkali-Burned Rat Cornea
Authors: Joung Chanmin , Noh Hyojin , Jung Jeein , Song Hwa Young , Bae Hwanse , Pahk Kisoo , Kim Won-Ki
Published: April 2020

The corneal fibrotic responses to corneal damage often lead to severe corneal opacification thereby resulting in severe visual impairment or even blindness. The persistence of corneal opacity depends heavily on the activity of corneal myofibroblast. Myofibroblasts are opaque and synthesize a disorganized extracellular matrix (ECM) and thus promoting opacification. Cluster of differentiation 147 (CD147), a member of the immunoglobulin superfamily, is known to play important roles in the differentiation process from fibroblast to myofibroblast in damaged cornea and may therefore be an effective target for treatment of corneal opacity. Here, we examined the therapeutic efficacy of novel CD147 inhibiting verbenone derivative SP-8356 ((1S,5R)-4-(3,4-dihydroxy-5-methoxystyryl)-6,6-dimethylbicyclo[3.1.1]hept-3-en-2-one) on corneal fibrosis. Topical SP-8356 significantly reduced corneal haze and fibrosis in the alkali-burned cornea. In detail, SP-8356 inhibited both alpha-smooth muscle actin (α-SMA) expressing myofibroblast and its ECM-related products, such as matrix-metalloproteinase-9 and collagen type III and IV. Similar to SP-8356, topical corticosteroid (prednisolone acetate, PA) also reduced the ECM-related products and opacification. However, prednisolone acetate failed to decrease the population of α-SMA-positive corneal myofibroblast. In conclusion, SP-8356 is capable enough to prevent corneal haze by preventing pathological fibrosis after severe corneal damage. Therefore, SP-8356 could be a potentially promising therapeutic drug for corneal fibrosis.
Current Advances in the Diagnostic Imaging of Atherosclerosis: Insights into the Pathophysiology of Vulnerable Plaque
Authors: Mushenkova Nataliya V. , Summerhill Volha I. , Zhang Dongwei , Romanenko Elena B. , Grechko Andrey V. , Orekhov Alexander N.
Published: April 2020

Atherosclerosis is a lipoprotein-driven inflammatory disorder leading to a plaque formation at specific sites of the arterial tree. After decades of slow progression, atherosclerotic plaque rupture and formation of thrombi are the major factors responsible for the development of acute coronary syndromes (ACSs). In this regard, the detection of high-risk (vulnerable) plaques is an ultimate goal in the management of atherosclerosis and cardiovascular diseases (CVDs). Vulnerable plaques have specific morphological features that make their detection possible, hence allowing for identification of high-risk patients and the tailoring of therapy. Plaque ruptures predominantly occur amongst lesions characterized as thin-cap fibroatheromas (TCFA). Plaques without a rupture, such as plaque erosions, are also thrombi-forming lesions on the most frequent pathological intimal thickening or fibroatheromas. Many attempts to comprehensively identify vulnerable plaque constituents with different invasive and non-invasive imaging technologies have been made. In this review, advantages and limitations of invasive and non-invasive imaging modalities currently available for the identification of plaque components and morphologic features associated with plaque vulnerability, as well as their clinical diagnostic and prognostic value, were discussed.
Extracellular Matrix Derived from High Metastatic Human Breast Cancer Triggers Epithelial-Mesenchymal Transition in Epithelial Breast Cancer Cells through αvβ3 Integrin
Authors: Machado Brandão-Costa Renata , Helal-Neto Edward , Maia Vieira Andreza , Barcellos-de-Souza Pedro , Morgado-Diaz Jose , Barja-Fidalgo Christina
Published: April 2020

Alterations in the composition and architecture of the extracellular matrix (ECM) can influence cancer growth and dissemination. During epithelial-mesenchymal transition (EMT), epithelial cells assume a mesenchymal cell phenotype, changing their adhesion profiles from cell-cell contacts to cell-matrix interactions, contributing to metastasis. Breast cancer cells present at different stages of differentiation, producing distinct ECMs in the same tumor mass. However, the contribution of ECM derived from metastatic tumor cells to EMT is unclear. Here, we showed the mechanisms involved in the interaction of MCF-7, a low-metastatic, epithelial breast cancer cell line, with the ECM produced by a high metastatic breast tumor cell, MDA-MB-231 (MDA-ECM). MDA-ECM induced morphological changes in MCF-7 cells, decreased the levels of E-cadherin, up-regulated mesenchymal markers, and augmented cell migration. These changes were accompanied by the activation of integrin-associated signaling, with increased phosphorylation of FAK, ERK, and AKT and activation canonical TGF-β receptor signaling, enhancing phosphorylation of SMAD2 and SMAD4 nuclear translocation in MCF-7 cells. Treatment with Kistrin (Kr), a specific ligand of integrin αvβ3 EMT induced by MDA-ECM, inhibited TGF-β receptor signaling in treated MCF-7 cells. Our results revealed that after interaction with the ECM produced by a high metastatic breast cancer cell, MCF-7 cells lost their characteristic epithelial phenotype undergoing EMT, an effect modulated by integrin signaling in crosstalk with TGF-β receptor signaling pathway. The data evidenced novel potential targets for antimetastatic breast cancer therapies.
Minimum Winter Temperature as a Limiting Factor of the Potential Spread of Agrilus planipennis, an Alien Pest of Ash Trees, in Europe
Authors: Orlova-Bienkowskaja Marina J. , Bieńkowski Andrzej O.
Published: April 2020

The emerald ash borer, EAB (Agrilus planipennis) is a devastating alien pest of ash trees. It is spreading in European Russia and Ukraine and will appear in other European countries. Our aim was to determine the regions of Europe where the winter temperature drops low enough to prevent A. planipennis establishment. We calculated the minimum daily air temperature from 2003–2019 for each grid square (0.5° × 0.5°) in East Asia, North America and Europe and determined the minimum daily temperature in the grid squares where A. planipennis was recorded. Temperatures of −30 to −33 °C occur in the northern portions of the pest range on all continents. No established population has been recorded in localities where temperatures below −34 °C occur. This temperature is close to the absolute supercooling point of A. planipennis larva (−35.3 °C). It is unlikely that low temperatures could prevent the spread of A. planipennis in northern Western Europe (Sweden, Norway, Finland, etc.), since the temperature in this area did not fall to −34 °C from 2003–2019. However, such temperatures are not rare in eastern European Russia (Kostroma, Vologda, Orenburg regions, etc.), where Fraxinus pennsylvanica and F. excelsior occur. These regions could potentially become refuges for these ash species.
Helmet CPAP to Treat Acute Hypoxemic Respiratory Failure in Patients with COVID-19: A Management Strategy Proposal
Authors: Radovanovic Dejan , Rizzi Maurizio , Pini Stefano , Saad Marina , Chiumello Davide Alberto , Santus Pierachille
Published: April 2020

Since the beginning of March 2020, the coronavirus disease 2019 (COVID-19) pandemic has caused more than 13,000 deaths in Europe, almost 54% of which has occurred in Italy. The Italian healthcare system is experiencing a stressful burden, especially in terms of intensive care assistance. In fact, the main clinical manifestation of COVID-19 patients is represented by an acute hypoxic respiratory failure secondary to bilateral pulmonary infiltrates, that in many cases, results in an acute respiratory distress syndrome and requires an invasive ventilator support. A precocious respiratory support with non-invasive ventilation or high flow oxygen should be avoided to limit the droplets’ air-dispersion and the healthcare workers’ contamination. The application of a continuous positive airway pressure (CPAP) by means of a helmet can represent an effective alternative to recruit diseased alveolar units and improve hypoxemia. It can also limit the room contamination, improve comfort for the patients, and allow for better clinical assistance with long-term tolerability. However, the initiation of a CPAP is not free from pitfalls. It requires a careful titration and monitoring to avoid a delayed intubation. Here, we discuss the rationale and some important considerations about timing, criteria, and monitoring requirements for patients with COVID-19 respiratory failure requiring a CPAP treatment.
Transcranial Direct Current Stimulation and Migraine—The Beginning of a Long Journey
Authors: Ayache Samar S. , Chalah Moussa A.
Published: April 2020

Migraine, a benign yet disturbing condition, is one of the frequent neurological disorders, affecting up to 15–20% of the worldwide population [...]
Resistance Mechanisms towards CD38−Directed Antibody Therapy in Multiple Myeloma
Authors: Franssen Laurens E. , Stege Claudia A. M. , Zweegman Sonja , van de Donk Niels W. C. J. , Nijhof Inger S.
Published: April 2020

Antibodies targeting CD38 are rapidly changing the treatment landscape of multiple myeloma (MM). CD38−directed antibodies have several mechanisms of action. Fc−dependent immune effector mechanisms include complement-dependent cytotoxicity (CDC), antibody−dependent cell−mediated cytotoxicity (ADCC), antibody-dependent cellular phagocytosis (ADCP) and apoptosis. In addition, direct effects and immunomodulatory effects contribute to the efficacy of CD38−directed antibodies. Daratumumab, the first−in−class anti−CD38 monoclonal antibody, is now part of standard treatment regimens of both newly diagnosed as well as relapsed/refractory MM patients. The FDA has recently approved isatuximab in combination with pomalidomide and dexamethasone for relapsed/refractory MM patients after at least two prior therapies. Further, the other CD38−targeting antibodies (i.e., MOR202 and TAK-079) are increasingly used in clinical trials. The shift to front-line treatment of daratumumab will lead to an increase in patients refractory to CD38 antibody therapy already after first−line treatment. Therefore, it is important to gain insight into the mechanisms of resistance to CD38−targeting antibodies in MM, and to develop strategies to overcome this resistance. In the current review, we will briefly describe the most important clinical data and mechanisms of action and will focus in depth on the current knowledge on mechanisms of resistance to CD38-targeting antibodies and potential strategies to overcome this.
Questionnaire on Perception of Threat from COVID-19
Authors: Pérez-Fuentes María del Carmen , Molero Jurado María del Mar , Oropesa Ruiz Nieves Fátima , Martos Martínez África , Simón Márquez María del Mar , Herrera-Peco Iván , Gázquez Linares José Jesús
Published: April 2020

The ravages caused by the disease known as COVID-19 has led to a worldwide healthcare and social emergency requiring an effective combined effort from everyone to reduce contagion. Under these circumstances, the perception of the disease is going to have a relevant role in the individual’s psychological adjustment. However, at the present time there is no validated instrument for evaluating adult perception of threat from COVID-19. Considering the importance of perception or representation of the disease in a state of social alert, our study intended to validate an instrument measuring the psychological process of the disease caused by the coronavirus (COVID-19). In view of the above, this study evaluated the factor structure and reliability of the version of the Illness Perception Questionnaire (IPQ) for COVID-19 in a sample of adults. The sample consisted of 1014 Spanish adults (67.2% women and 32.8% men). The exploratory and confirmatory factor analyses supported a unidimensional model of the scale, which was the one that showed the best fit and explained 43.87% of the variance. This brief version has adequate psychometric properties and may be used to evaluate the perception of threat from COVID-19 in an adult Spanish population. The validation of this instrument contributes to progress in representation of COVID-19 in our culture.
Iron Deficiency: Impact on Functional Capacity and Quality of Life in Heart Failure with Preserved Ejection Fraction
Authors: Alcaide-Aldeano Alex , Garay Alberto , Alcoberro Lídia , Jiménez-Marrero Santiago , Yun Sergi , Tajes Marta , García-Romero Elena , Díez-López Carles , González-Costello José , Mateus-Porta Gemma , Cainzos-Achirica Miguel , Enjuanes Cristina , Comín-Colet Josep , Moliner Pedro
Published: April 2020

The effects of iron deficiency (ID) have been widely studied in heart failure (HF) with reduced ejection fraction. On the other hand, studies in HF with preserved ejection fraction (HFpEF) are few and have included small numbers of participants. The aim of this study was to assess the role that ID plays in functional capacity and quality of life (QoL) in HFpEF while comparing several iron-related biomarkers to be used as potential predictors. ID was defined as ferritin <100 ng/mL or transferrin saturation <20%. Submaximal exercise capacity, measured by the 6-min walking test (6MWT), and QoL, assessed by the Minnesotta Living with Heart Failure Questionnaire (MLHFQ), were compared between iron deficient patients and patients with normal iron status. A total of 447 HFpEF patients were included in the present cross-sectional study, and ID prevalence was 73%. Patients with ID performed worse in the 6MWT compared to patients with normal iron status (ID 271 ± 94 m vs. non-ID 310 ± 108 m, p < 0.01). They also scored higher in the MLHFQ, denoting worse QoL (ID 49 ± 22 vs. non-ID 43 ± 23, p = 0.01). Regarding iron metabolism biomarkers, serum soluble transferrin receptor (sTfR) was the strongest independent predictor of functional capacity (β = −63, p < 0.0001, R2 0.39) and QoL (β = 7.95, p < 0.0001, R2 0.14) in multivariate models. This study postulates that ID is associated with worse functional capacity and QoL in HFpEF as well, and that sTfR is the best iron-related biomarker to predict both. Our study also suggests that the effects of ID could differ among HFpEF patients by left ventricular ejection fraction.
Long Non-Coding RNAs in Biliary Tract Cancer—An Up-to-Date Review
Authors: Bekric Dino , Neureiter Daniel , Ritter Markus , Jakab Martin , Gaisberger Martin , Pichler Martin , Kiesslich Tobias , Mayr Christian
Published: April 2020

The term long non-coding RNA (lncRNA) describes non protein-coding transcripts with a length greater than 200 base pairs. The ongoing discovery, characterization and functional categorization of lncRNAs has led to a better understanding of the involvement of lncRNAs in diverse biological and pathological processes including cancer. Aberrant expression of specific lncRNA species was demonstrated in various cancer types and associated with unfavorable clinical characteristics. Recent studies suggest that lncRNAs are also involved in the development and progression of biliary tract cancer, a rare disease with high mortality and limited therapeutic options. In this review, we summarize current findings regarding the manifold roles of lncRNAs in biliary tract cancer and give an overview of the clinical and molecular consequences of aberrant lncRNA expression as well as of underlying regulatory functions of selected lncRNA species in the context of biliary tract cancer.
Radiofrequency Chondroplasty May Not Have a Long-Lasting Effect in the Treatment of Concomitant Grade II Patellar Cartilage Defects in Humans
Authors: Koller Ulrich , Springer Bernhard , Rentenberger Colleen , Szomolanyi Pavol , Waldstein Wenzel , Windhager Reinhard , Trattnig Siegfried , Apprich Sebastian
Published: April 2020

The effect of radiofrequency chondroplasty on cartilage tissue is not well studied. This prospective pilot study investigates the effect of radiofrequency chondroplasty on International Cartilage Repair Society (ICRS) grade II patellar cartilage defects using high-resolution magnetic resonance imaging (MRI) with T2 mapping. Six consecutive patients were treated for ICRS grade II patellar cartilage defects using radiofrequency chondroplasty. Before surgery and at defined follow-ups (2 weeks, 4 and 12 months) a high-resolution morphological 3 Tesla MRI with quantitative T2 mapping was performed. At baseline MRI, global T2 values of cartilage defects were increased (46.8 ms ± 9.7) compared to healthy cartilage (35.2 ms ± 4.5) in the same knee which served as reference. Two weeks after treatment, global T2 values (39.2 ms ± 7.7) of the defect areas decreased. However, global T2 values of the defect areas increased beyond the preoperative levels at 4 months (47.4 ms ± 3.1) and 12 months (51.5 ms ± 5.9), respectively. Zonal T2 mapping revealed that the predominant changes in T2 values occurred at the superficial cartilage layer. T2 mapping appears to be an ideal method to monitor cartilage degeneration after chondroplasty. Based on the small sample size of this pilot study, radiofrequency chondroplasty may cause cartilage damage and may not have a long-lasting effect in the treatment of grade II patellar cartilage defects. In five out of six patients, postoperative cartilage damage was observed on quantitative MRI. This study was therefore terminated before completion. We recommend only addressing the pathology which indicated arthroscopy and leaving concomitant cartilage lesions untreated.
Viral Loads in Ocular Fluids of Acute Retinal Necrosis Eyes Infected by Varicella-Zoster Virus Treated with Intravenous Acyclovir Treatment
Authors: Sato Tomohito , Yamamoto Wataru , Tanaka Atsushi , Shimazaki Haruna , Sugita Sunao , Kaburaki Toshikatsu , Takeuchi Masaru
Published: April 2020

Acute retinal necrosis (ARN) is a rare viral endophthalmitis, and human herpesvirus is the principal pathogen. Early diagnosis and treatment are critical to avoid visual impairment by ARN, and pars plana vitrectomy (PPV) is required in advanced cases. In this study, we evaluated the transition of viral load in ocular fluids of ARN eyes with varicella-zoster virus (VZV) after intravenous acyclovir treatment. Fourteen eyes of 13 patients were analyzed retrospectively. All patients received intravenous acyclovir treatment, and eventually, all eyes underwent PPV. A polymerase chain reaction (PCR) test showed a 100% detection rate in all aqueous humor samples collected before the treatment (Pre-AH), as well as aqueous humor (Post-AH) and vitreous fluid samples (VF), collected during PPV conducted after the treatment. Within eight days or less of acyclovir treatment, viral loads both in AH and VF did not decrease significantly. Furthermore, the viral load of Pre-AH had a strong correlation with that of VH. These data suggest that in ARN eyes with VZV infection, the AH sample for the PCR test was reliable to confirm the pathogen. We propose that short-term treatment of intravenous acyclovir may be insufficient for reducing intraocular viral load, and the Pre-AH sample could be a predictor of viral activity in the eyes after acyclovir treatment.
Integrative Analysis and Machine Learning Based Characterization of Single Circulating Tumor Cells
Authors: Iyer Arvind , Gupta Krishan , Sharma Shreya , Hari Kishore , Lee Yi , Ramalingam Neevan , Yap Yoon , West Jay , Bhagat Ali , Subramani Balaram , Sabuwala Burhanuddin , Tan Tuan , Thiery Jean , Jolly Mohit , Ramalingam Naveen , Sengupta Debarka
Published: April 2020

We collated publicly available single-cell expression profiles of circulating tumor cells (CTCs) and showed that CTCs across cancers lie on a near-perfect continuum of epithelial to mesenchymal (EMT) transition. Integrative analysis of CTC transcriptomes also highlighted the inverse gene expression pattern between PD-L1 and MHC, which is implicated in cancer immunotherapy. We used the CTCs expression profiles in tandem with publicly available peripheral blood mononuclear cell (PBMC) transcriptomes to train a classifier that accurately recognizes CTCs of diverse phenotype. Further, we used this classifier to validate circulating breast tumor cells captured using a newly developed microfluidic system for label-free enrichment of CTCs.
Temperament and Character Traits of Female Eating Disorder Patients with(out) Non-Suicidal Self-Injury
Authors: Buelens Tinne , Luyckx Koen , Verschueren Margaux , Schoevaerts Katrien , Dierckx Eva , Depestele Lies , Claes Laurence
Published: April 2020

Eating disorder (ED) patients show alarmingly high prevalence rates of Non-Suicidal Self-Injury (NSSI). Adolescents seem to be particularly at risk, as EDs and NSSI both have their onset in mid-adolescence. It has been suggested that personality could be a transdiagnostic mechanism underlying both EDs and NSSI. However, little attention has been given to adolescent clinical samples compared to adult and/or community samples. Therefore, the current study investigated the role of personality in a sample of 189 female inpatients with an ED (M = 15.93, SD = 0.98). Our results confirmed the high prevalence of NSSI in EDs, specifically in patients with bingeing/purging behaviours (ED-BP). Temperamental differences were found between ED-BP and the restrictive ED subtype (ED-R). Namely, ED-BP patients showed more harm avoidance and less self-directedness compared to ED-R. Temperamental differences were found in NSSI as well, regardless of ED subtype: ED patients who had engaged in NSSI during their lifetime reported less self-directedness and more harm avoidance. Interestingly, only ED patients who recently engaged in NSSI showed less novelty seeking. These temperamental profiles should be recognised as key mechanisms in the treatment of adolescent ED patients with and without NSSI.
Mucoadhesive Chitosan Delivery System with Chelidonii Herba Lyophilized Extract as a Promising Strategy for Vaginitis Treatment
Authors: Paczkowska Magdalena , Chanaj-Kaczmarek Justyna , Romaniuk-Drapała Aleksandra , Rubiś Błażej , Szymanowska Daria , Kobus-Cisowska Joanna , Szymańska Emilia , Winnicka Katarzyna , Cielecka-Piontek Judyta
Published: April 2020

Chelidonium majus (also known as celandine) contains pharmacologically active compounds such as isoquinoline alkaloids (e.g., chelidonine, sanguinarine), flavonoids, saponins, carotenoids, and organic acids. Due to the presence of isoquinoline alkaloids, Chelidonii herba extracts are widely used as an antibacterial, antifungal, antiviral (including HSV-1 and HIV-1), and anti-inflammatory agent in the treatment of various diseases, while chitosan is a biocompatible and biodegradable carrier with valuable properties for mucoadhesive formulations preparation. Our work aimed to prepare mucoadhesive vaginal drug delivery systems composed of Chelidonii herba lyophilized extract and chitosan as an effective way to treat vaginitis. The pharmacological safety of usage of isoquinoline alkaloids, based on MTT test, were evaluated for the maximum doses 36.34 ± 0.29 µg/mL and 0.89 ± 1.16 µg/mL for chelidonine and sanguinarine, respectively. Dissolution rate profiles and permeability through artificial membranes for chelidonine and sanguinarine after their introduction into the chitosan system were studied. The low permeability for used save doses of isoquinoline alkaloids and results of microbiological studies allow confirmation that system Chelidonii herba lyophilized extract chitosan 80/500 1:1 (w/w) is a promising strategy for vaginal use. Ex vivo studies of mucoadhesive properties and evaluation of tableting features demonstrated that the formulation containing Chelidonii herba lyophilized extract (120.0 mg) with chitosan (80/500—100.0 mg) and polymer content (HPMC—100.0 mg, microcrystalline cellulose—50.0 mg, lactose monohydrate—30.0 mg and magnesium stearate—4.0 mg) is a vaginal dosage form with prolonging dissolution profile and high mucoadhesion properties (up to 4 h).
Clinical and Radiologic Features Together Better Predict Lung Nodule Malignancy in Patients with Soft-Tissue Sarcoma
Authors: Tetta Cecilia , Giugliano Antonio , Tonetti Laura , Rocca Michele , Longhi Alessandra , Londero Francesco , Parise Gianmarco , Parise Orlando , Micali Linda Renata , La Meir Mark , Maessen Jos G. , Gelsomino Sandro
Published: April 2020

We test the hypothesis that a model including clinical and computed tomography (CT) features may allow discrimination between benign and malignant lung nodules in patients with soft-tissue sarcoma (STS). Seventy-one patients with STS undergoing their first lung metastasectomy were examined. The performance of multiple logistic regression models including CT features alone, clinical features alone, and combined features, was tested to evaluate the best model in discriminating malignant from benign nodules. The likelihood of malignancy increased by more than 11, 2, 6 and 7 fold, respectively, when histological synovial sarcoma sub-type was associated with the following CT nodule features: size ≥ 5.6 mm, well defined margins, increased size from baseline CT, and new onset at preoperative CT. Likewise, in the case of grade III primary tumor, the odds ratio (OR) increased by more than 17 times when the diameter of pulmonary nodules (PNs) was >5.6 mm, more than 13 times with well-defined margins, more than 7 times with PNs increased from baseline CT, and more than 20 times when there were new-onset nodules. Finally, when CT nodule was ≥5.6 in size, it had well-defined margins, it increased in size from baseline CT, and when new onset nodules at preoperative CT were concomitant to residual primary tumor R2, the risk of malignancy increased by more than 10, 6, 25 and 28 times, respectively. The combination of clinical and CT features has the highest predictive value for detecting the malignancy of pulmonary nodules in patients with soft tissue sarcoma, allowing early detection of nodule malignancy and treatment options.