bluuebunny/crossref_metadata_2025 huggingface dataset:
Heterogeneity of Metabolic Vulnerability in Imatinib-Resistant Gastrointestinal Stromal Tumor
Authors: Huang Wen-Kuan , Gao Jiwei , Chen Ziqing , Shi Hao , Yuan Juan , Cui Huanhuan L. , Yeh Chun-Nan , Bränström Robert , Larsson Catharina , Li Shuijie , Lui Weng-Onn
Published: May 2020

Metabolic reprogramming is a hallmark of cancer cells in response to targeted therapy. Decreased glycolytic activity with enhanced mitochondrial respiration secondary to imatinib has been shown in imatinib-sensitive gastrointestional stromal tumors (GIST). However, the role of energy metabolism in imatinib-resistant GIST remains poorly characterized. Here, we investigated the effect of imatinib treatment on glycolysis and oxidative phosphorylation (OXPHOS), as well as the effect of inhibition of these energy metabolisms on cell viability in imatinib-resistant and -sensitive GIST cell lines. We observed that imatinib treatment increased OXPHOS in imatinib-sensitive, but not imatinib-resistant, GIST cells. Imatinib also reduced the expression of mitochondrial biogenesis activators (peroxisome proliferator-activated receptor coactivator-1 alpha (PGC1α), nuclear respiratory factor 2 (NRF2), and mitochondrial transcription factor A (TFAM)) and mitochondrial mass in imatinib-sensitive GIST cells. Lower TFAM levels were also observed in imatinib-sensitive GISTs than in tumors from untreated patients. Using the Seahorse system, we observed bioenergetics diversity among the GIST cell lines. One of the acquired resistant cell lines (GIST 882R) displayed a highly metabolically active phenotype with higher glycolysis and OXPHOS levels compared with the parental GIST 882, while the other resistant cell line (GIST T1R) had a similar basal glycolytic activity but lower mitochondrial respiration than the parental GIST T1. Further functional assays demonstrated that GIST 882R was more vulnerable to glycolysis inhibition than GIST 882, while GIST T1R was more resistant to OXPHOS inhibition than GIST T1. These findings highlight the diverse energy metabolic adaptations in GIST cells that allow them to survive upon imatinib treatment and reveal the potential of targeting the metabolism for GIST therapy.
The Network of Angiotensin Receptors in Breast Cancer
Authors: Acconcia Filippo
Published: May 2020

The renin-angiotensin system (RAS) is a network of proteins regulating many aspects of human physiology, including cardiovascular, pulmonary, and immune system physiology. The RAS is a complicated network of G-protein coupled receptors (GPCRs) (i.e., AT1R, AT2R, MASR, and MRGD) orchestrating the effects of several hormones (i.e., angiotensin II, angiotensin (1–7), and alamandine) produced by protease-based transmembrane receptors (ACE1 and ACE2). Two signaling axes have been identified in the RAS endocrine system that mediate the proliferative actions of angiotensin II (i.e., the AT1R-based pathway) or the anti-proliferative effects of RAS hormones (i.e., the AT2R-, MAS-, and MRGD-based pathways). Disruption of the balance between these two axes can cause different diseases (e.g., cardiovascular pathologies and the severe acute respiratory syndrome coronavirus 2- (SARS-CoV-2)-based COVID-19 disease). It is now accepted that all the components of the RAS endocrine system are expressed in cancer, including cancer of the breast. Breast cancer (BC) is a multifactorial pathology for which there is a continuous need to identify novel drugs. Here, I reviewed the possible roles of both axes of the RAS endocrine network as potential druggable pathways in BC. Remarkably, the analysis of the current knowledge of the different GPCRs of the RAS molecular system not only confirms that AT1R could be considered a drug target and that its inhibition by losartan and candesartan could be useful in the treatment of BC, but also identifies Mas-related GPCR member D (MRGD) as a druggable protein. Overall, the RAS of GPCRs offers multifaceted opportunities for the development of additional compounds for the treatment of BC.
Reactive Oxygen Species and Redox Signaling in Chronic Kidney Disease
Authors: Irazabal Maria V. , Torres Vicente E.
Published: May 2020

Chronic kidney disease (CKD) remains a worldwide public health problem associated with serious complications and increased mortality rates. Accumulating evidence indicates that elevated intracellular levels of reactive oxygen species (ROS) play a major role in the pathogenesis of CKD. Increased intracellular levels of ROS can lead to oxidation of lipids, DNA, and proteins, contributing to cellular damage. On the other hand, ROS are also important secondary messengers in cellular signaling. Consequently, normal kidney cell function relies on the “right” amount of ROS. Mitochondria and NADPH oxidases represent major sources of ROS in the kidney, but renal antioxidant systems, such as superoxide dismutase, catalase, or glutathione peroxidase counterbalance ROS-mediated injury. This review discusses the main sources of ROS and antioxidant systems in the kidney, and redox signaling pathways leading to inflammation and fibrosis, which result in abnormal kidney function and CKD progression. We further discuss the important role of the nuclear factor erythroid 2-related factor 2 (Nrf2) in regulating antioxidant responses, and other mechanisms of redox signaling.
Modeling Height–Diameter Relationships for Mixed-Species Plantations of Fraxinus mandshurica Rupr. and Larix olgensis Henry in Northeastern China
Authors: Xie Longfei , Widagdo Faris Rafi Almay , Dong Lihu , Li Fengri
Published: May 2020

The mixture of tree species has gradually become the focus of forest research, especially native species mixing. Mixed-species plantations of Manchurian ash (Fraxinus mandshurica Rupr.) and Changbai larch (Larix olgensis Henry) have successfully been cultivated in Northeast China. Height–diameter (H–D) models were found to be effective in designing the silvicultural planning for mixed-species plantations. Thus, this study aimed to develop a new system of H–D models for juvenile ash and larch mixed-species plantations, based on competition information and tree and stand attributes. The leave-one-out cross-validation was utilized for model validation. The result showed that the H–D relationship was affected not only by the tree attributes (i.e., tree size and competition information) but also by stand characteristics, such as site quality and species proportion of basal area. The best model explained more than 80% and 85% variation of the tree height of ash and larch, respectively. Moreover, model validation also confirmed the high accuracy of the newly developed model’s predictions. We also found that, in terms of total tree height, ash in middle rows were higher than those in side rows, while larch in the middle rows were higher in the early growth period but then became lower than those in the side rows, as the diameter increased. The newly established H–D models would be useful for forestry inventory practice and have the potential to aid decisions in mixed-species plantations of ash and larch.
Simulating Resource Management across the Cloud-to-Thing Continuum: A Survey and Future Directions
Authors: Bendechache Malika , Svorobej Sergej , Takako Endo Patricia , Lynn Theo
Published: May 2020

In recent years, there has been significant advancement in resource management mechanisms for cloud computing infrastructure performance in terms of cost, quality of service (QoS) and energy consumption. The emergence of the Internet of Things has led to the development of infrastructure that extends beyond centralised data centers from the cloud to the edge, the so-called cloud-to-thing continuum (C2T). This infrastructure is characterised by extreme heterogeneity, geographic distribution, and complexity, where the key performance indicators (KPIs) for the traditional model of cloud computing may no longer apply in the same way. Existing resource management mechanisms may not be suitable for such complex environments and therefore require thorough testing, validation and evaluation before even being considered for live system implementation. Similarly, previously discounted resource management proposals may be more relevant and worthy of revisiting. Simulation is a widely used technique in the development and evaluation of resource management mechanisms for cloud computing but is a relatively nascent research area for new C2T computing paradigms such as fog and edge computing. We present a methodical literature analysis of C2T resource management research using simulation software tools to assist researchers in identifying suitable methods, algorithms, and simulation approaches for future research. We analyse 35 research articles from a total collection of 317 journal articles published from January 2009 to March 2019. We present our descriptive and synthetic analysis from a variety of perspectives including resource management, C2T layer, and simulation.
Clotting Properties of Onopordum tauricum (Willd.) Aqueous Extract in Milk of Different Species
Authors: Mozzon Massimo , Foligni Roberta , Mannozzi Cinzia , Zamporlini Federica , Raffaelli Nadia , Aquilanti Lucia
Published: May 2020

Plant proteases used in cheesemaking are easily available and could increase the acceptability of cheeses, otherwise hindered by ethical issues (e.g., religions, dietary habits, aversion to genetically engineered food and food ingredients). The milk clotting potential of Onopordum tauricum (Willd.) aqueous extract as an alternative to animal rennet was assessed for the first time in milk of different species (ewe, goat, cow). Among the aerial anatomical parts, i.e., receptacle, leaves, stems, and flowers, only the latter ones showed clotting properties. A response surface methodology (RSM) was used to explore the effects of three independent variables (temperature, pH, volume of coagulant) on the milk clotting activity (MCA) of the flower extract. A second-order polynomial model adequately described the experimental data and predicted a temperature value of 55 °C, a pH value of 4.9–5.7, and a volume of coagulant of 300–500 μL (added to 5 mL of milk) as optimal conditions to maximize the MCA. At a 35 °C temperature and natural milk pH of 6.7–6.8, the estimated MCA of the O. tauricum extract was 72–87, 69–86, and 75–151, in goat’s, ewe’s, and cow’s milk, respectively. In comparison, the MCA of calf rennet was 5.4–4.9, 3.3–14.7, and 4.9–16.7 times higher than that of the plant extract in goat’s, ewe’s, and cow’s milk, respectively.
Changes in the Content and Bioavailability of Onion Quercetin and Grape Resveratrol During In Vitro Human Digestion
Authors: Lee Seung Yun , Lee Seung Jae , Yim Dong Gyun , Hur Sun Jin
Published: May 2020

We investigated the effects of in vitro human digestion on the content and bioavailability of onion quercetin and grape resveratrol caused by the composition of saliva or gastric, duodenal, or bile juice. We observed the digestibility of extracted onion quercetin and grape resveratrol, respectively, in the small intestine of the in vitro human digestion system. By liquid chromatography–mass spectroscopy, we found that the degradation of quercetin and resveratrol was influenced by small intestine digestion. Before and after in vitro human digestion, the 2,2-diphenyl-1-picrylhydrazyl (DPPH) radical scavenging activities of homogenized water- and ethanol-extracted grapes were higher than those of onion extracts. DPPH radical scavenging activity in both quercetin and resveratrol was decreased by in vitro digestion. These results will improve our understanding of how human digestion influences the contents and free radical scavenging activities of quercetin and resveratrol.
NIPT Technique Based on the Use of Long Chimeric DNA Reads
Authors: Belova Vera , Plakhina Daria , Evfratov Sergey , Tsukanov Kirill , Khvorykh Gennady , Rakitko Alexander , Konoplyannikov Alexander , Ilinsky Valery , Rebrikov Denis , Korostin Dmitriy
Published: May 2020

Non-invasive prenatal testing (NIPT) for aneuploidy on Chromosomes 21 (T21), 18 (T18) and 13 (T13) is actively used in clinical practice around the world. One of the limitations of the wider implementation of this test is the high cost of the analysis itself, as high-throughput sequencing is still relatively expensive. At the same time, there is an increasing trend in the length of reads yielded by sequencers. Since extracellular DNA is short, in the order of 140–160 bp, it is not possible to effectively use long reads. The authors used high-performance sequencing of cell-free DNA (cfDNA) libraries that went through additional stages of enzymatic fragmentation and random ligation of the resulting products to create long chimeric reads. The authors used a controlled set of samples to analyze a set of cfDNA samples from pregnant women with a high risk of fetus aneuploidy according to the results of the first trimester screening and confirmed by invasive karyotyping of the fetus using laboratory and analytical approaches developed by the authors. They evaluated the sensitivity, specificity, PPV (positive predictive value), and NPV (negative predictive value) of the results. The authors developed a technique for constructing long chimeric reads from short cfDNA fragments and validated the test using a control set of extracellular DNA samples obtained from pregnant women. The obtained sensitivity and specificity parameters of the NIPT developed by the authors corresponded to the approaches proposed earlier (99.93% and 99.14% for T21; 100% and 98.34% for T18; 100% and 99.17% for T13, respectively).
Interpreting Mixture Profiles: Comparison Between Precision ID GlobalFiler™ NGS STR Panel v2 and Traditional Methods
Authors: Ragazzo Michele , Carboni Stefania , Caputo Valerio , Buttini Carlotta , Manzo Laura , Errichiello Valeria , Puleri Giulio , Giardina Emiliano
Published: May 2020

Forensic investigation for the identification of offenders, recognition of human remains, and verification of family relationships requires the analysis of particular types of highly informative DNA markers, which have high discriminatory power and are efficient for typing degraded samples. These markers, called STRs (Short Tandem Repeats), can be amplified by multiplex-PCR (Polymerase Chain Reaction) allowing attainment of a unique profile through which it is possible to distinguish one individual from another with a high statistical significance. The rapid and progressive evolution of analytical techniques and the advent of Next-Generation Sequencing (NGS) have completely revolutionized the DNA sequencing approach. This technology, widely used today in the diagnostic field, has the advantage of being able to process several samples in parallel, producing a huge volume of data in a short time. At this time, although default parameters of interpretation software are available, there is no general agreement on the interpretation rules of forensic data produced via NGS technology. Here we report a pilot study aimed for a comparison between NGS (Precision ID GlobalFiler™ NGS STR Panel v2, Thermo Fisher Scientific, Waltham, MA, USA) and traditional methods in their ability to identify major and minor contributors in DNA mixtures from saliva and urine samples. A quantity of six mixed samples were prepared for both saliva and urine samples from donors. A total of 12 mixtures were obtained in the ratios of 1:2; 1:4; 1:6; 1:8; 1:10; and 1:20 between minor and major contributors. Although the number of analyzed mixtures is limited, our results confirm that NGS technology offers a huge range of additional information on samples, but cannot ensure a higher sensitivity in respect to traditional methods. Finally, the Precision ID GlobalFiler™ NGS STR Panel v2 is a powerful method for kinship analyses and typing reference samples, but its use in biological evidence should be carefully considered on the basis of the characteristics of the evidence.
CDK-Independent and PCNA-Dependent Functions of p21 in DNA Replication
Authors: Mansilla Sabrina Florencia , De La Vega María Belén , Calzetta Nicolás Luis , Siri Sebastián Omar , Gottifredi Vanesa
Published: May 2020

p21Waf/CIP1 is a small unstructured protein that binds and inactivates cyclin-dependent kinases (CDKs). To this end, p21 levels increase following the activation of the p53 tumor suppressor. CDK inhibition by p21 triggers cell-cycle arrest in the G1 and G2 phases of the cell cycle. In the absence of exogenous insults causing replication stress, only residual p21 levels are prevalent that are insufficient to inhibit CDKs. However, research from different laboratories has demonstrated that these residual p21 levels in the S phase control DNA replication speed and origin firing to preserve genomic stability. Such an S-phase function of p21 depends fully on its ability to displace partners from chromatin-bound proliferating cell nuclear antigen (PCNA). Vice versa, PCNA also regulates p21 by preventing its upregulation in the S phase, even in the context of robust p21 induction by γ irradiation. Such a tight regulation of p21 in the S phase unveils the potential that CDK-independent functions of p21 may have for the improvement of cancer treatments.
Epigenetic Factors that Control Pericentric Heterochromatin Organization in Mammals
Authors: Fioriniello Salvatore , Marano Domenico , Fiorillo Francesca , D’Esposito Maurizio , Della Ragione Floriana
Published: May 2020

Pericentric heterochromatin (PCH) is a particular form of constitutive heterochromatin that is localized to both sides of centromeres and that forms silent compartments enriched in repressive marks. These genomic regions contain species-specific repetitive satellite DNA that differs in terms of nucleotide sequences and repeat lengths. In spite of this sequence diversity, PCH is involved in many biological phenomena that are conserved among species, including centromere function, the preservation of genome integrity, the suppression of spurious recombination during meiosis, and the organization of genomic silent compartments in the nucleus. PCH organization and maintenance of its repressive state is tightly regulated by a plethora of factors, including enzymes (e.g., DNA methyltransferases, histone deacetylases, and histone methyltransferases), DNA and histone methylation binding factors (e.g., MECP2 and HP1), chromatin remodeling proteins (e.g., ATRX and DAXX), and non-coding RNAs. This evidence helps us to understand how PCH organization is crucial for genome integrity. It then follows that alterations to the molecular signature of PCH might contribute to the onset of many genetic pathologies and to cancer progression. Here, we describe the most recent updates on the molecular mechanisms known to underlie PCH organization and function.
Pitt-Hopkins Syndrome: Clinical and Molecular Findings of a 5-Year-Old Patient
Authors: Tripon Florin , Bogliș Alina , Micheu Cristian , Streață Ioana , Bănescu Claudia
Published: May 2020

Pitt Hopkins syndrome (PTHS) is a very rare condition and until now, approximately 500 patients were reported worldwide, of which not all are genetically confirmed. Usually, individuals with variants affecting exons 1 to 5 in the TCF4 gene associate mild intellectual disability (ID), between exons 5 to 8, moderate to severe ID and sometimes have some of the characteristics of PTHS, and variants starting from exon 9 to exon 20 associate a typical PTHS phenotype. In this report, we describe the clinical and molecular findings of a Caucasian boy diagnosed with PTHS. PTHS phenotype is described including craniofacial dysmorphism with brachycephaly, biparietal narrowing, wide nasal bridge, thin and linear lateral eyebrows, palpebral edema, full cheeks, short philtrum, wide mouth with prominent and everted lips, prominent Cupid’s bow, downturned corners of the mouth, microdontia and also the clinical management of the patient. The previously and the current diagnosis scores are described in this report and also the challenges and their benefits for an accurate and early diagnosis.
Duplication in ECR near HMX1 and a SNP in GATA6 Genes Regulate Microtia in Awassi Sheep
Authors: Jawasreh Khaleel I. Z. , Al-Omari Haitham Daif-Allah
Published: May 2020

Microtia and anotia are hereditary traits characterized by an underdevelopment or complete absence of the outer ear. These congenital malformations observed in many species can exist as part of various syndromes or as an isolated trait as seen in the fat-tailed Awassi sheep breed. Our study aims to identify the genetic mutations causing microtia in Awassi sheep by DNA sequencing. DNA was extracted from blood samples randomly collected from 84 Awassi sheep (16 earless, 41 short ear and 27 normal ear) across different farms. GATA6 exons 1, 2, 4, 6 and 7, CLRN1 intron 3, DCC intron 2, ECR near HMX1 and the intergenic region between GATA6 and MIB1 genes were screened, amplified and sequenced. Allele and genotype frequencies were calculated by direct counting. Association was performed using chi-squared test for goodness-of-fit. Results showed mutations in only two genes significantly associated with microtia in Awassi: duplication in part of ECR near HMX1 (6:114293121-6:114293196) and a SNP at GATA6 exon 7 (23:34498242). Association results revealed that the ECR locus accounts for the microtia phenotype, while GATA6 exon 7 acts as a modifier gene. Genetic screening for these loci can be used to improve selection against microtia in Awassi sheep.
Epidemiological Trend of Sepsis in Patients with Hospital Admissions Related to Hepatitis C in Spain (2000–2015): A Nationwide Study
Authors: Alvaro-Meca Alejandro , Maté-Cano Irene , Ryan Pablo , Briz Verónica , Resino Salvador
Published: May 2020

Background: Hepatitis C virus (HCV) infection predisposes patients to other infectious diseases, such as sepsis. We aimed to analyze epidemiological trends of sepsis-related admissions, deaths, and costs in hospital admissions with chronic hepatitis C who had a hospital admission in Spain. Methods: We performed a retrospective study of all hospitalizations involving chronic hepatitis C in the Spanish Minimum Basic Data Set (MBDS) between 2000 and 2015. This period was divided into four calendar periods (2000–2004, 2005–2007, 2008–2011, and 2012–2015). Results: We selected 868,523 hospital admissions of patients with chronic hepatitis C over 16 years in the Spanish MBDS. Among them, we found 70,976 (8.17%) hospital admissions of patients who developed sepsis, of which 13,915 (19.61%) died during admission. We found an upward trend, from 2000–2003 to 2012–2015, in the rate of sepsis-related admission (from 6.18% to 10.64%; p < 0.001), the risk of sepsis-related admission (from 1.31 to 1.55; p < 0.001), and the sepsis-related cost per hospital admission (from 7198€ to above 9497€; p < 0.001). However, we found a downward trend during the same study period in the sepsis case-fatality rate (from 21.99% to 18.16%; p < 0.001), the risk of sepsis-related death (from 0.81 to 0.56; p < 0.001), and the length of hospital stay (LOHS) (from 16.9 to 13.9; p < 0.001). Moreover, the rate of bacterial Gram-positive and candidiasis infections decreased, while Gram-negative microorganisms increased from 2000–2003 to 2012–2015. Conclusions: Sepsis, in chronic hepatitis C patients admitted to the hospital, has increased the period 2000–2015 and has been an increasing burden for the Spanish public health system. However, there has also been a significant reduction in lethality and LOHS during the study period. In addition, the most prevalent specific microorganisms have also changed in this period.
Gender, Albuminuria and Chronic Kidney Disease Progression in Treated Diabetic Kidney Disease
Authors: Fernandez-Fernandez Beatriz , Mahillo Ignacio , Sanchez-Rodriguez Jinny , Carriazo Sol , Sanz Ana B. , Sanchez-Niño Maria Dolores , Ortiz Alberto
Published: May 2020

Background: Women are reported to have a lower incidence of renal replacement therapy, despite a higher prevalence of chronic kidney disease (CKD). Aim: To analyze diabetic kidney disease (DKD) progression in men and women. Methods: Prospective cohort: n = 261, 35% women, new consecutive nephrology DKD referrals. Results: Women smoked less and better complied with the dietary phosphate and sodium restrictions. Despite a less frequent nephrology referral, women had lower baseline albuminuria. Over a 30 ± 10-month follow-up, albuminuria decreased in women and the estimated glomerular filtration rate (eGFR) loss was slower than in men. However, the percentage of rapid progressors was similar in both sexes. The best multivariate model predicting rapid progression in men (area under curve (AUC) = 0.92) and women differed. Albuminuria and fractional excretion of phosphate (FEphosphate) were part of the men multivariable model, but not of women. The AUC for the prediction of rapid progression by albuminuria was higher in men than in women, and the albuminuria cut-off points also differed. In women, there was a higher percentage of rapid progressors who had baseline physiological albuminuria. Conclusions: Female DKD differs from male DKD: albuminuria was milder and better responsive to therapy, the loss of eGFR was slower and the predictors of rapid progression differed from men: albuminuria was a better predictor in men than in women. Lifestyle factors may contribute to the differences.
Analysis of Usage Data from a Self-Guided App-Based Virtual Reality Cognitive Behavior Therapy for Acrophobia: A Randomized Controlled Trial
Authors: Donker Tara , van Klaveren Chris , Cornelisz Ilja , Kok Robin N. , van Gelder Jean-Louis
Published: May 2020

This study examined user engagement with ZeroPhobia, a self-guided app-based virtual reality (VR) Cognitive Behavior Therapy for acrophobia symptoms using cardboard VR viewers. Dutch acrophobic adults (n = 96) completed assessments at baseline and immediately following treatment. Primary outcome measures were the Acrophobia Questionnaire (AQ) and the Igroup Presence Questionnaire (IPQ). Usage data consisted of number of VR sessions practiced, practice time, and fear ratings directly after practicing. Results show that of the 66 participants who played at least one level, the majority continued to finish all levels, spending on average 24.4 min in VR. Self-reported fear consistently decreased between the start and finish of levels. Post-test AQ scores depended quadratically on time spent in VR. Higher pre-test AQ scores were significantly associated with subjective anxiety after the first level and a reduction of post-test AQ scores, but not with number of sessions, suggesting it might be more beneficial to play one level for a longer time period instead of practicing many VR levels. Results also show an optimum exposure level at which increasing practice time does not result in increased benefit. Self-guided VR acrophobia treatment is effective and leads to consistent reductions in self-reported anxiety both between levels and after treatment. Most participants progressed effectively to the highest self-exposure level, despite the absence of a therapist.
Enhanced Resorption of Liposomal Packed Vitamin C Monitored by Ultrasound
Authors: Prantl Lukas , Eigenberger Andreas , Gehmert Sebastian , Haerteis Silke , Aung Thiha , Rachel Reinhard , Jung Ernst Michael , Felthaus Oliver
Published: May 2020

Vitamin C is an essential nutrient for humans and is involved in a plethora of health-related functions. Several studies have shown a connection between vitamin C intake and an improved resistance to infections that involves the immune system. However, the body cannot store vitamin C and both the elevated oral intake, and the intravenous application have certain disadvantages. In this study, we wanted to show a new formulation for the liposomal packaging of vitamin C. Using freeze etching electron microscopy, we show the formed liposomes. With a novel approach of post-processing procedures of real-time sonography that combines enhancement effects by contrast-like ultrasound with a transducer, we wanted to demonstrate the elevated intestinal vitamin C resorption on four participants. With the method presented in this study, it is possible to make use of the liposomal packaging of vitamin C with simple household materials and equipment for intake elevation. For the first time, we show the enhanced resorption of ingested liposomes using microbubble enhanced ultrasound imaging.
Retinal Vascular Changes in Radiation Maculopathy after Intravitreal Ranibizumab by Optical Coherence Tomography Angiography
Authors: Cennamo Gilda , Montorio Daniela , Bernardo Roberta , Farella Antonio , Liuzzi Raffaele , Breve Maria Angelica , Reibaldi Michele , Cennamo Giovanni
Published: May 2020

In this prospective study, we investigated the structural and vascular retinal changes at baseline and after Ranibizumab injections at the last follow up to one year in patients affected by Radiation Maculopathy (RM) after plaque brachytheraphy in choroidal melanoma, using Spectral Domain Optical Coherence Tomography (SD-OCT) and OCT Angiography (OCTA). A total of 40 eyes with RM of 40 patients (18 females, 22 males, mean age 51.9 ± 11 years) that underwent ruthenium-106 plaque brachytherapy were included. All patients received one monthly intravitreal injection of Ranibizumab (Pro Re Nata regimen). We analyzed the Foveal Avascular Zone (FAZ) area, the retinal vessel density (VD) of the superficial capillary plexus (SCP) and of the deep capillary plexus (DCP), using OCTA, and we detected the Central Foveal Thickness (CFT) by SD-OCT at baseline and after treatment. At the last follow up, we found a significant improvement of the CFT (p < 0.001) while OCTA parameters revealed no change in VD of the SCP (p = 0.402), DCP (p = 0.282), and FAZ area (p = 0.255), resulting in a stabilization of the visual acuity (p = 0.210) respect to baseline. The absence of functional improvement, despite the anatomical recovery of the macula, could be due to the absence of improvement in FAZ area and in retinal VD after treatment. OCTA parameters could represent predictive biomarkers to anti-vascular endothelial growth factor (anti-VEGF) intravitreal response and to help to better understand the physiopathological mechanisms of the RM.
A Translational In Vivo and In Vitro Metabolomic Study Reveals Altered Metabolic Pathways in Red Blood Cells of Type 2 Diabetes
Authors: Palomino-Schätzlein Martina , Lamas-Domingo Rubén , Ciudin Andreea , Gutiérrez-Carcedo Patricia , Marés Rosó , Aparicio-Gómez Carolina , Hernández Cristina , Simó Rafael , Herance José Raúl
Published: May 2020

Clinical parameters used in type 2 diabetes mellitus (T2D) diagnosis and monitoring such as glycosylated haemoglobin (HbA1c) are often unable to capture important information related to diabetic control and chronic complications. In order to search for additional biomarkers, we performed a pilot study comparing T2D patients with healthy controls matched by age, gender, and weight. By using 1H-nuclear magnetic resonance (NMR) based metabolomics profiling of red blood cells (RBCs), we found that the metabolic signature of RBCs in T2D subjects differed significantly from non-diabetic controls. Affected metabolites included glutathione, 2,3-bisphophoglycerate, inosinic acid, lactate, 6-phosphogluconate, creatine and adenosine triphosphate (ATP) and several amino acids such as leucine, glycine, alanine, lysine, aspartate, phenylalanine and tyrosine. These results were validated by an independent cohort of T2D and control patients. An analysis of the pathways in which these metabolites were involved showed that energetic and redox metabolism in RBCs were altered in T2D, as well as metabolites transported by RBCs. Taken together, our results revealed that the metabolic profile of RBCs can discriminate healthy controls from T2D patients. Further research is needed to determine whether metabolic fingerprint in RBC could be useful to complement the information obtained from HbA1c and glycemic variability as well as its potential role in the diabetes management.
Combined Coronary CT-Angiography and TAVI-Planning: A Contrast-Neutral Routine Approach for Ruling-Out Significant Coronary Artery Disease
Authors: Gohmann Robin F. , Lauten Philipp , Seitz Patrick , Krieghoff Christian , Lücke Christian , Gottschling Sebastian , Mende Meinhard , Weiß Stefan , Wilde Johannes , Kiefer Philipp , Noack Thilo , Desch Steffen , Holzhey David , Borger Michael A. , Thiele Holger , Abdel-Wahab Mohamed , Gutberlet Matthias
Published: May 2020

Background: Significant coronary artery disease (CAD) is a common finding in patients undergoing transcatheter aortic valve implantation (TAVI). Assessment of CAD prior to TAVI is recommended by current guidelines and is mainly performed via invasive coronary angiography (ICA). In this study we analyzed the ability of coronary CT-angiography (cCTA) to rule out significant CAD (stenosis ≥ 50%) during routine pre-TAVI evaluation in patients with high pre-test probability for CAD. Methods: In total, 460 consecutive patients undergoing pre-TAVI CT (mean age 79.6 ± 7.4 years) were included. All patients were examined with a retrospectively ECG-gated CT-scan of the heart, followed by a high-pitch-scan of the vascular access route utilizing a single intravenous bolus of 70 mL iodinated contrast medium. Images were evaluated for image quality, calcifications, and significant CAD; CT-examinations in which CAD could not be ruled out were defined as positive (CAD+). Routinely, patients received ICA (388/460; 84.3%; Group A), which was omitted if renal function was impaired and CAD was ruled out on cCTA (Group B). Following TAVI, clinical events were documented during the hospital stay. Results: cCTA was negative for CAD in 40.2% (188/460). Sensitivity, specificity, PPV, and NPV in Group A were 97.8%, 45.2%, 49.6%, and 97.4%, respectively. Median coronary artery calcium score (CAC) was higher in CAD+-patients but did not have predictive value for correct classification of patients with cCTA. There were no significant differences in clinical events between Group A and B. Conclusion: cCTA can be incorporated into pre-TAVI CT-evaluation with no need for additional contrast medium. cCTA may exclude significant CAD in a relatively high percentage of these high-risk patients. Thereby, cCTA may have the potential to reduce the need for ICA and total amount of contrast medium applied, possibly making pre-procedural evaluation for TAVI safer and faster.
Regulation of Angiogenesis Discriminates Tissue Resident MSCs from Effective and Defective Osteogenic Environments
Authors: Cuthbert R. J. , Jones E. , Sanjurjo-Rodríguez C. , Lotfy A. , Ganguly P. , Churchman S. M. , Kastana P. , Tan H. B. , McGonagle D. , Papadimitriou E. , Giannoudis P. V.
Published: May 2020

Background: The biological mechanisms that contribute to atrophic long bone non-union are poorly understood. Multipotential mesenchymal stromal cells (MSCs) are key contributors to bone formation and are recognised as important mediators of blood vessel formation. This study examines the role of MSCs in tissue formation at the site of atrophic non-union. Materials and Methods: Tissue and MSCs from non-union sites (n = 20) and induced periosteal (IP) membrane formed following the Masquelet bone reconstruction technique (n = 15) or bone marrow (n = 8) were compared. MSC content, differentiation, and influence on angiogenesis were measured in vitro. Cell content and vasculature measurements were performed by flow cytometry and histology, and gene expression was measured by quantitative polymerase chain reaction (qPCR). Results: MSCs from non-union sites had comparable differentiation potential to bone marrow MSCs. Compared with induced periosteum, non-union tissue contained similar proportion of colony-forming cells, but a greater proportion of pericytes (p = 0.036), and endothelial cells (p = 0.016) and blood vessels were more numerous (p = 0.001) with smaller luminal diameter (p = 0.046). MSCs showed marked differences in angiogenic transcripts depending on the source, and those from induced periosteum, but not non-union tissue, inhibited early stages of in vitro angiogenesis. Conclusions: In vitro, non-union site derived MSCs have no impairment of differentiation capacity, but they differ from IP-derived MSCs in mediating angiogenesis. Local MSCs may thus be strongly implicated in the formation of the immature vascular network at the non-union site. Attention should be given to their angiogenic support profile when selecting MSCs for regenerative therapy.
Prevalence and Comorbidity of Atopic Dermatitis in Children: A Large-Scale Population Study Based on Real-World Data
Authors: Gilaberte Yolanda , Pérez-Gilaberte Juan Blas , Poblador-Plou Beatriz , Bliek-Bueno Kevin , Gimeno-Miguel Antonio , Prados-Torres Alexandra
Published: May 2020

This study aimed at exploring atopic dermatitis (AD) prevalence in children and exhaustively analyzing their comorbidity. We conducted a descriptive analysis of their socio-demographic and comorbidity characteristics in the EpiChron Cohort (Aragón, Spain). Adjusted odds ratios (OR) were calculated for each comorbidity using logistic regression models. In total, 33,591 children had a diagnosis of AD, resulting in an overall prevalence of 15.5%. AD prevalence was higher in girls compared to boys, in 3–9-year-olds compared to children of other ages, and in Spanish children compared to those of other nationalities. Multimorbidity was present in 43% of children, with the most frequent chronic comorbidities being asthma (13.1%), psychosocial disorders (7.9%), and visual impairment (7.8%). Many diseases were, regardless of their prevalence, statistically associated with AD. The strongest associations (odds ratio (OR) (95% confidence interval (CI))) were found in asthma (2.10 (2.02–2.17)), allergic rhinitis (2.00 (1.91–2.10)), and irritable bowel syndrome (1.90 (1.56–2.31)). A better understanding of the array of comorbidities associated with AD in children might help improve their clinical management. Future longitudinal studies are encouraged to shed light on the potential underlying pathophysiological mechanisms involved in the identified associations.
Association between Non-Alcoholic Fatty Liver Disease and Chronic Kidney Disease: A Cross-Sectional Study
Authors: Akahane Takemi , Akahane Manabu , Namisaki Tadashi , Kaji Kosuke , Moriya Kei , Kawaratani Hideto , Takaya Hiroaki , Sawada Yasuhiko , Shimozato Naotaka , Fujinaga Yukihisa , Furukawa Masanori , Kitagawa Koh , Ozutsumi Takahiro , Tsuji Yuki , Kaya Daisuke , Mitoro Akira , Yoshiji Hitoshi
Published: May 2020

It is unclear whether the link between non-alcoholic fatty liver disease (NAFLD) and chronic kidney disease (CKD) is mediated by common risk factors. We aimed to elucidate the association between NAFLD and CKD using propensity score (PS)-matched analysis. We assessed 3725 Japanese individuals, excluding those with hepatitis B or C infection and men and women who consumed >30 and >20 g/day of alcohol, respectively. Of these, we enrolled 1097 Japanese subjects with NAFLD diagnosed by ultrasonography and 1097 PS-matched subjects without NAFLD. The prevalence of CKD was higher in subjects with NAFLD than in those without NAFLD before PS matching, but there was no significant difference between these groups in terms of CKD prevalence after PS matching. There was no difference in the prevalence of CKD between those with and without NAFLD in the subgroup analyses. Logistic regression analysis demonstrated that obesity, hypertension, and hyperuricemia were independent predictors of CKD, but NAFLD was not independently associated with CKD. In subjects with NAFLD, obesity, hypertension, and hyperuricemia were independent predictors of CKD. Thus, the link between NAFLD and CKD may be mediated by common risk factors. We recommend screening for CKD when patients with NAFLD have the aforementioned comorbidities.
Introducing the Journal of Nuclear Engineering: An Interdisciplinary Open Access Journal Dedicated to Publishing Research in Nuclear and Radiation Sciences and Applications
Authors: Cacuci Dan
Published: May 2020

In 1938, Strassmann, Hahn and Meitner discovered neutron-induced nuclear fission in uranium, forever changing our world and opening multiple paths to developing nuclear energy, nuclear medicine, instrumentation, space propulsion, environmental monitoring, remediation and nuclear security [...]
Yield and Metabolite Production of Pelargonium sidoides DC. in Response to Irrigation and Nitrogen Management
Authors: Mofokeng Motiki , Prinsloo Gerhard , Araya Hintsa , du Plooy Christian , Sathekge Ntshakga , Amoo Stephen , Steyn J.
Published: May 2020

Competition for water between agricultural and non-agricultural economic sectors hampers agricultural production, especially in water-scarce regions. Understanding crop responses in terms of yield and quality to irrigation is an important factor in designing appropriate irrigation management for optimal crop production and quality. Pelargonium sidoides DC., often harvested from the wild, is in high demand in the informal market and for commercial formulations. Agricultural production of high-quality materials through cultivation can help reduce pressure on its wild populations. This study aimed at determining the effects of water and nitrogen on P. sidoides yield and metabolite production. The irrigation treatments applied were 30%, 50%, and 70% of an allowable depletion level (ADL), while the nitrogen (N) levels were 0 (control), 50, 100, and 150 kg ha−1. The 30% ADL resulted in a significantly higher biomass and root yield. Nitrogen at 50 and 100 kg ha−1 resulted in a significantly higher biomass yield, compared to the N control. An increase in sugars and citrate cycle components was observed for the well-watered 30% ADL treatment, whereas water-stressed (50% and 70% ADL) treatments increased alanine, aspartate, and glutamate metabolism, increasing levels of asparagine, 4-aminobutyrate, and arginine. The treatments had no significant effect on the root content of esculin, scopoletin, and umckalin. Water stress induced metabolite synthesis to mitigate the stress condition, whereas under no water stress primary metabolites were synthesized. Moreover, cultivation of P. sidoides as a conservation strategy can increase yield without affecting its bioactivity, while providing sustenance for the rural communities.
Editorial for the Special Issue “Innovative and Applied Research on Platinum-Group and Rare Earth Elements”
Authors: Economou-Eliopoulos Maria , Zaccarini Federica , Garuti Giorgio
Published: May 2020

This Special Issue “Innovative and Applied Research on Platinum-group and Rare Earth Elements” is dedicated to the work and memory of Demetrios Eliopoulos, IGME (Institute of Geology and Mineral Exploration), Greece who passed away on 19 April 2019 [...]
Time Series Clustering: A Complex Network-Based Approach for Feature Selection in Multi-Sensor Data
Authors: Bonacina Fabrizio , Miele Eric Stefan , Corsini Alessandro
Published: May 2020

Distributed monitoring sensor networks are used in an ever increasing number of applications, particularly with the advent of IoT technologies. This has led to a growing demand for unconventional analytical tools to cope with a large amount of different signals. In this scenario, the modeling of time series in similar groups represents an interesting area especially for feature subset selection (FSS) purposes. Methods based on clustering algorithms are very promising for FSS, but in their original form they are unsuitable to manage the complexity of temporal dynamics in time series. In this paper we propose a clustering approach, based on complex network analysis, for the unsupervised FSS of time series in sensor networks. We used natural visibility graphs to map signal segments in the network domain, then extracted features in the form of node degree sequences of the graphs, and finally computed time series clustering through community detection algorithms. The approach was tested on multivariate signals monitored in a 1 MW cogeneration plant and the results show that it outperforms standard time series clustering in terms of both redundancy reduction and information gain. In addition, the proposed method demonstrated its merit in terms of retention of information content with respect to the original dataset in the analyzed condition monitoring system.
Synthesis, Crystal Structures and Luminescence Properties of Three New Cadmium 3D Coordination Polymers
Authors: Ju Hai-Yan , Zhang Gang , Yang Ming , Liu De-Zheng , Yang Yong-Sheng , Zhang Yan-Bo
Published: May 2020

The new rigid planar ligand 2,5-bis(3-(pyridine-4-yl)phenyl)thiazolo[5,4-d]thiazole (BPPT) has been synthesized, which is an excellent building block for assembling coordination polymer. Under solvothermal reaction conditions, cadmium ion with BPPT in the presence of various carboxylic acids including (1,1′-biphenyl)-4,4′-dicarboxylic acid (BPDC), isophthalic acid (IP), and benzene-1,3,5-tricarboxylic acid (BTC) gave rise to three coordination complexes, viz, [Cd(BPPT)(BPDA)](BPPT)n (1), [Cd(BPPT) (IP)] (CH3OH) (2), and [Cd3(BPPT)3(BTC)2(H2O)2] (3). The structures of 1, 2, and 3 were characterized by single crystal X-ray diffraction. The IR spectra as well as thermogravimetric and luminescence properties were also investigated. Complex 1 is a two-dimensional (2D) network and further stretched to a 3D supramolecular structure through π–π stacking interaction. The complexes 2 and 3 show 3D framework. The complexes 1, 2, and 3 exhibited luminescence property at room temperature.
Collective Locomotion of Human Cells, Wound Healing and Their Control by Extracts and Isolated Compounds from Marine Invertebrates
Authors: Luparello Claudio , Mauro Manuela , Lazzara Valentina , Vazzana Mirella
Published: May 2020

The collective migration of cells is a complex integrated process that represents a common theme joining morphogenesis, tissue regeneration, and tumor biology. It is known that a remarkable amount of secondary metabolites produced by aquatic invertebrates displays active pharmacological properties against a variety of diseases. The aim of this review is to pick up selected studies that report the extraction and identification of crude extracts or isolated compounds that exert a modulatory effect on collective cell locomotion and/or skin tissue reconstitution and recapitulate the molecular, biochemical, and/or physiological aspects, where available, which are associated to the substances under examination, grouping the producing species according to their taxonomic hierarchy. Taken all of the collected data into account, marine invertebrates emerge as a still poorly-exploited valuable resource of natural products that may significantly improve the process of skin regeneration and restrain tumor cell migration, as documented by in vitro and in vivo studies. Therefore, the identification of the most promising invertebrate-derived extracts/molecules for the utilization as new targets for biomedical translation merits further and more detailed investigations.