bluuebunny/crossref_metadata_2025 huggingface dataset:
TATSSI: A Free and Open-Source Platform for Analyzing Earth Observation Products with Quality Data Assessment
Authors: Tecuapetla-Gómez Inder , López-Saldaña Gerardo , Cruz-López María Isabel , Ressl Rainer
Published: April 2021

Earth observation (EO) data play a crucial role in monitoring ecosystems and environmental processes. Time series of satellite data are essential for long-term studies in this context. Working with large volumes of satellite data, however, can still be a challenge, as the computational environment with respect to storage, processing and data handling can be demanding, which sometimes can be perceived as a barrier when using EO data for scientific purposes. In particular, open-source developments which comprise all components of EO data handling and analysis are still scarce. To overcome this difficulty, we present Tools for Analyzing Time Series of Satellite Imagery (TATSSI), an open-source platform written in Python that provides routines for downloading, generating, gap-filling, smoothing, analyzing and exporting EO time series. Since TATSSI integrates quality assessment and quality control flags when generating time series, data quality analysis is the backbone of any analysis made with the platform. We discuss TATSSI’s 3-layered architecture (data handling, engine and three application programming interfaces (API)); by allowing three APIs (a native graphical user interface, some Jupyter Notebooks and the Python command line) this development is exceptionally user-friendly. Furthermore, to demonstrate the application potential of TATSSI, we evaluated MODIS time series data for three case studies (irrigation area changes, evaluation of moisture dynamics in a wetland ecosystem and vegetation monitoring in a burned area) in different geographical regions of Mexico. Our analyses were based on methods such as the spatio-temporal distribution of maxima over time, statistical trend analysis and change-point decomposition, all of which were implemented in TATSSI. Our results are consistent with other scientific studies and results in these areas and with related in-situ data.
The Urokinase Receptor: A Multifunctional Receptor in Cancer Cell Biology. Therapeutic Implications
Authors: Li Santi Anna , Napolitano Filomena , Montuori Nunzia , Ragno Pia
Published: April 2021

Proteolysis is a key event in several biological processes; proteolysis must be tightly controlled because its improper activation leads to dramatic consequences. Deregulation of proteolytic activity characterizes many pathological conditions, including cancer. The plasminogen activation (PA) system plays a key role in cancer; it includes the serine-protease urokinase-type plasminogen activator (uPA). uPA binds to a specific cellular receptor (uPAR), which concentrates proteolytic activity at the cell surface, thus supporting cell migration. However, a large body of evidence clearly showed uPAR involvement in the biology of cancer cell independently of the proteolytic activity of its ligand. In this review we will first describe this multifunctional molecule and then we will discuss how uPAR can sustain most of cancer hallmarks, which represent the biological capabilities acquired during the multistep cancer development. Finally, we will illustrate the main data available in the literature on uPAR as a cancer biomarker and a molecular target in anti-cancer therapy.
Vincristine-Induced Peripheral Neuropathy (VIPN) in Pediatric Tumors: Mechanisms, Risk Factors, Strategies of Prevention and Treatment
Authors: Triarico Silvia , Romano Alberto , Attinà Giorgio , Capozza Michele Antonio , Maurizi Palma , Mastrangelo Stefano , Ruggiero Antonio
Published: April 2021

Vincristine-induced peripheral neurotoxicity (VIPN) is a very common side effect of vincristine chemotherapy among pediatric patients with cancer. Neuropathy may be sensory, motor and/or autonomic, with consequent reduction, delay or discontinuation of vincristine-chemotherapy, but also pain, disability, reduced quality of life of patients and an increase in medical costs. Vincristine acts out its antineoplastic function by altering the normal assembly and disassembly of microtubules, with their consequent mitosis block and death. Vincristine leads to VIPN through a complex mechanism of damage, which occurs not only on the microtubules, but also on the endothelium and the mitochondria of nerve cells. Furthermore, both patient-related risk factors (age, race, ethnicity and genetic polymorphisms) and treatment-related risk factors (dose, time of infusion and drug–drug interactions) are involved in the pathogenesis of VIPN. There is a lack of consensus about the prophylaxis and treatment of VIPN among pediatric oncologic patients, despite several molecules (such as gabapentin, pyridoxine and pyridostigmine, glutamic acid and glutamine) having been already investigated in clinical trials. This review describes the molecular mechanisms of VIPN and analyzes the risk factors and the principal drugs adopted for the prophylaxis and treatment of VIPN in pediatric patients with cancer.
Glucose Metabolism in Osteoblasts in Healthy and Pathophysiological Conditions
Authors: Donat Antonia , Knapstein Paul-Richard , Jiang Shan , Baranowsky Anke , Ballhause Tobias-Malte , Frosch Karl-Heinz , Keller Johannes
Published: April 2021

Bone tissue in vertebrates is essential to performing movements, to protecting internal organs and to regulating calcium homeostasis. Moreover, bone has also been suggested to contribute to whole-body physiology as an endocrine organ, affecting male fertility; brain development and cognition; and glucose metabolism. A main determinant of bone quality is the constant remodeling carried out by osteoblasts and osteoclasts, a process consuming vast amounts of energy. In turn, clinical conditions associated with impaired glucose metabolism, including type I and type II diabetes and anorexia nervosa, are associated with impaired bone turnover. As osteoblasts are required for collagen synthesis and matrix mineralization, they represent one of the most important targets for pharmacological augmentation of bone mass. To fulfill their function, osteoblasts primarily utilize glucose through aerobic glycolysis, a process which is regulated by various molecular switches and generates adenosine triphosphate rapidly. In this regard, researchers have been investigating the complex processes of energy utilization in osteoblasts in recent years, not only to improve bone turnover in metabolic disease, but also to identify novel treatment options for primary bone diseases. This review focuses on the metabolism of glucose in osteoblasts in physiological and pathophysiological conditions.
Antibody Libraries as Tools to Discover Functional Antibodies and Receptor Pleiotropism
Authors: Lin Chih-Wei , Lerner Richard A.
Published: April 2021

Most antibodies currently in use have been selected based on their binding affinity. However, nowadays, antibodies that can not only bind but can also alter the function of cell surface signaling components are increasingly sought after as therapeutic drugs. Therefore, the identification of such functional antibodies from a large antibody library is the subject of intensive research. New methods applied to combinatorial antibody libraries now allow the isolation of functional antibodies in the cellular environment. These selected agonist antibodies have provided new insights into important issues of signal transduction. Notably, when certain antibodies bind to a given receptor, the cell fate induced by them may be the same or different from that induced by natural agonists. In addition, combined with phenotypic screening, this platform allows us to discover unexpected experimental results and explore various phenomena in cell biology, such as those associated with stem cells and cancer cells.
Induction of Axonal Outgrowth in Mouse Hippocampal Neurons via Bacterial Magnetosomes
Authors: De Vincentiis Sara , Falconieri Alessandro , Mickoleit Frank , Cappello Valentina , Schüler Dirk , Raffa Vittoria
Published: April 2021

Magnetosomes are membrane-enclosed iron oxide crystals biosynthesized by magnetotactic bacteria. As the biomineralization of bacterial magnetosomes can be genetically controlled, they have become promising nanomaterials for bionanotechnological applications. In the present paper, we explore a novel application of magnetosomes as nanotool for manipulating axonal outgrowth via stretch-growth (SG). SG refers to the process of stimulation of axonal outgrowth through the application of mechanical forces. Thanks to their superior magnetic properties, magnetosomes have been used to magnetize mouse hippocampal neurons in order to stretch axons under the application of magnetic fields. We found that magnetosomes are avidly internalized by cells. They adhere to the cell membrane, are quickly internalized, and slowly degrade after a few days from the internalization process. Our data show that bacterial magnetosomes are more efficient than synthetic iron oxide nanoparticles in stimulating axonal outgrowth via SG.
Emerging Roles of Gut Virome in Pediatric Diseases
Authors: Fulci Valerio , Stronati Laura , Cucchiara Salvatore , Laudadio Ilaria , Carissimi Claudia
Published: April 2021

In the last decade, the widespread application of shotgun metagenomics provided extensive characterization of the bacterial “dark matter” of the gut microbiome, propelling the development of dedicated, standardized bioinformatic pipelines and the systematic collection of metagenomic data into comprehensive databases. The advent of next-generation sequencing also unravels a previously underestimated viral population (virome) present in the human gut. Despite extensive efforts to characterize the human gut virome, to date, little is known about the childhood gut virome. However, alterations of the gut virome in children have been linked to pathological conditions such as inflammatory bowel disease, type 1 diabetes, malnutrition, diarrhea and celiac disease.
An Integrated—Omics/Chemistry Approach Unravels Enzymatic and Spontaneous Steps to Form Flavoalkaloidal Nudicaulin Pigments in Flowers of Papaver nudicaule L.
Authors: Dudek Bettina , Warskulat Anne-Christin , Vogel Heiko , Wielsch Natalie , Menezes Riya Christina , Hupfer Yvonne , Paetz Christian , Gebauer-Jung Steffi , Svatoš Aleš , Schneider Bernd
Published: April 2021

Flower colour is an important trait for plants to attract pollinators and ensure their reproductive success. Among yellow flower pigments, the nudicaulins in Papaver nudicaule L. (Iceland poppy) are unique due to their rarity and unparalleled flavoalkaloid structure. Nudicaulins are derived from pelargonidin glycoside and indole, products of the flavonoid and indole/tryptophan biosynthetic pathway, respectively. To gain insight into the molecular and chemical basis of nudicaulin biosynthesis, we combined transcriptome, differential gel electrophoresis (DIGE)-based proteome, and ultra-performance liquid chromatography–high resolution mass spectrometry (UPLC-HRMS)-based metabolome data of P. nudicaule petals with chemical investigations. We identified candidate genes and proteins for all biosynthetic steps as well as some key metabolites across five stages of petal development. Candidate genes of amino acid biosynthesis showed a relatively stable expression throughout petal development, whereas most candidate genes of flavonoid biosynthesis showed increasing expression during development followed by downregulation in the final stage. Notably, gene candidates of indole-3-glycerol-phosphate lyase (IGL), sharing characteristic sequence motifs with known plant IGL genes, were co-expressed with flavonoid biosynthesis genes, and are probably providing free indole. The fusion of indole with pelargonidin glycosides was retraced synthetically and promoted by high precursor concentrations, an excess of indole, and a specific glycosylation pattern of pelargonidin. Thus, nudicaulin biosynthesis combines the enzymatic steps of two different pathways with a spontaneous fusion of indole and pelargonidin glycoside under precisely tuned reaction conditions.
Role of α2-Adrenoceptor Subtypes in Suppression of L-Type Ca2+ Current in Mouse Cardiac Myocytes
Authors: Evdokimovskii Edward V. , Jeon Ryounghoon , Park Sungjo , Pimenov Oleg Y. , Alekseev Alexey E.
Published: April 2021

Sarcolemmal α2 adrenoceptors (α2-AR), represented by α2A, α2B and α2C isoforms, can safeguard cardiac muscle under sympathoadrenergic surge by governing Ca2+ handling and contractility of cardiomyocytes. Cardiomyocyte-specific targeting of α2-AR would provide cardiac muscle-delimited stress control and enhance the efficacy of cardiac malfunction treatments. However, little is known about the specific contribution of the α2-AR subtypes in modulating cardiomyocyte functions. Herein, we analyzed the expression profile of α2A, α2B and α2C subtypes in mouse ventricle and conducted electrophysiological antagonist assay evaluating the contribution of these isoforms to the suppression of L-type Ca2+ current (ICaL). Patch-clamp electro-pharmacological studies revealed that the α2-agonist-induced suppression of ICaL involves mainly the α2C, to a lesser extent the α2B, and not the α2A isoforms. RT-qPCR evaluation revealed the presence of adra2b and adra2c (α2B and α2C isoform genes, respectively), but was unable to identify the expression of adra2a (α2A isoform gene) in the mouse left ventricle. Immunoblotting confirmed the presence only of the α2B and the α2C proteins in this tissue. The identified α2-AR isoform-linked regulation of ICaL in the mouse ventricle provides an important molecular substrate for the cardioprotective targeting.
Chemical, Thermal, Time, and Enzymatic Stability of Silk Materials with Silk I Structure
Authors: Zhao Meihui , Qi Zhenzhen , Tao Xiaosheng , Newkirk Chad , Hu Xiao , Lu Shenzhou
Published: April 2021

The crystalline structure of silk fibroin Silk I is generally considered to be a metastable structure; however, there is no definite conclusion under what circumstances this crystalline structure is stable or the crystal form will change. In this study, silk fibroin solution was prepared from B. Mori silkworm cocoons, and a combined method of freeze-crystallization and freeze-drying at different temperatures was used to obtain stable Silk I crystalline material and uncrystallized silk material, respectively. Different concentrations of methanol and ethanol were used to soak the two materials with different time periods to investigate the effect of immersion treatments on the crystalline structure of silk fibroin materials. X-ray diffraction (XRD), Fourier transform infrared spectroscopy (FTIR), Raman scattering spectroscopy (Raman), Scanning electron microscope (SEM), and Thermogravimetric analysis (TGA) were used to characterize the structure of silk fibroin before and after the treatments. The results showed that, after immersion treatments, uncrystallized silk fibroin material with random coil structure was transformed into Silk II crystal structure, while the silk material with dominated Silk I crystal structure showed good long-term stability without obvious transition to Silk II crystal structure. α-chymotrypsin biodegradation study showed that the crystalline structure of silk fibroin Silk I materials is enzymatically degradable with a much lower rate compared to uncrystallized silk materials. The crystalline structure of Silk I materials demonstrate a good long-term stability, endurance to alcohol sterilization without structural changes, and can be applied to many emerging fields, such as biomedical materials, sustainable materials, and biosensors.
High-Quality Nucleic Acid Isolation from Hard-to-Lyse Bacterial Strains Using PMAP-36, a Broad-Spectrum Antimicrobial Peptide
Authors: Cho Hye-sun , Choi Munjeong , Lee Yunjung , Jeon Hyoim , Ahn Byeongyong , Soundrarajan Nagasundarapandian , Hong Kwonho , Kim Jin-Hoi , Park Chankyu
Published: April 2021

The efficiency of existing cell lysis methods to isolate nucleic acids from diverse bacteria varies depending on cell wall structures. This study tested a novel idea of using broad-spectrum antimicrobial peptides to improve the lytic efficiency of hard-to-lyse bacteria and characterized their differences. The lysis conditions of Staphylococcus aureus using recombinant porcine myeloid antimicrobial peptide 36 (PMAP-36), a broad-spectrum pig cathelicidin, was optimized, and RNA isolation was performed with cultured pellets of ten bacterial species using various membranolytic proteins. Additionally, three other antimicrobial peptides, protegrin-1 (PG-1), melittin, and nisin, were evaluated for their suitability as the membranolytic agents of bacteria. However, PMAP-36 use resulted in the most successful outcomes in RNA isolation from diverse bacterial species. The amount of total RNA obtained using PMAP-36 increased by ~2-fold compared to lysozyme in Salmonella typhimurium. Streptococci species were refractory to all lytic proteins tested, although the RNA yield from PMAP-36 treatment was slightly higher than that from other methods. PMAP-36 use produced high-quality RNA, and reverse transcription PCR showed the efficient amplification of the 16S rRNA gene from all tested strains. Additionally, the results of genomic DNA isolation were similar to those of RNA isolation. Thus, our findings present an additional option for high quality and unbiased nucleic acid isolation from microbiomes or challenging bacterial strains.
An Academic Text Recommendation Method Based on Graph Neural Network
Authors: Yu Jie , Pan Chenle , Li Yaliu , Wang Junwei
Published: April 2021

Academic text recommendation, as a kind of text recommendation, has a wide range of application prospects. Predicting texts of interest to scholars in different fields based on anonymous sessions is a challenging problem. However, the existing session-based method only considers the sequential information, and pays more attention to capture the session purpose. The relationship between adjacent items in the session is not noticed. Specifically in the field of session-based text recommendation, the most important semantic relationship of text is not fully utilized. Based on the graph neural network and attention mechanism, this paper proposes a session-based text recommendation model (TXT-SR) incorporating the semantic relations, which is applied to the academic field. TXT-SR makes full use of the tightness of semantic connections between adjacent texts. We have conducted experiments on two real-life academic datasets from CiteULike. Experimental results show that TXT-SR has better effectiveness than existing session-based recommendation methods.
Dose–Response Assay for Synthetic Mosquito (Diptera: Culicidae) Attractant Using a High-Throughput Screening System
Authors: Kim Dae-Yun , Leepasert Theerachart , Bangs Michael J. , Chareonviriyaphap Theeraphap
Published: April 2021

Natural volatile host cues play a critical role for mosquito orientation and locating a blood source for egg production. Similar olfactory activation responses have allowed the use and development of artificial chemical attractants to lure mosquitoes to trapping devices. Using a pre-formulated commercial product mixture of different attractant chemicals, a high-throughput screening system (HITSS) is used to screen varying doses of chemical required to activate behavioral responses. Two strains of Aedes aegypti (L.): permethrin-susceptible (USDA) and -resistant (Pu Teuy) phenotypes and one Culex quinquefasciatus Say. (NIH) laboratory strain were tested. Overall, mosquitoes showed repellency between 1.0 g and to 10.0 g dose of each compound. However, by progressively reducing the dose, Cx. quinquefasciatus showed a greater positive percent attraction (88.9%) at 0.025 g, whereas the USDA and Pu Teuy Ae. aegypti produced optimum attractant activation at 0.005 g (72.6% and 58.9%, respectively) without significant difference within species (p > 0.05). In parallel control assays, Cx. quinquefasciatus was significantly attracted to 1 g of dry ice (carbon dioxide) (76%) more than Ae. aegypti (USDA) (12.2%). The HITSS was originally designed to measure three chemical actions to sublethal concentrations of chemicals by mosquitoes: toxicity and the two primary behavior avoidance responses (contact excitation and spatial repellency). These findings demonstrate that the HITSS assay, with only minor modifications, allows comparison screening of candidate compounds as potential attractants for anemotactic responses under laboratory-controlled conditions. Further investigations will be required to equate measurements obtained from controlled laboratory assays to more varied field conditions for attracting natural mosquito populations.
The Effects of Exposure to Flupyradifurone on Survival, Development, and Foraging Activity of Honey Bees (Apis mellifera L.) under Field Conditions
Authors: Guo Yi , Diao Qing-Yun , Dai Ping-Li , Wang Qiang , Hou Chun-Sheng , Liu Yong-Jun , Zhang Li , Luo Qi-Hua , Wu Yan-Yan , Gao Jing
Published: April 2021

Flupyradifurone (FPF) is a novel systemic nAChR agonist that interferes with signal transduction in the central nervous system of sucking pests. Despite claims that FPF is potentially “bee-safe” by risk assessments, laboratory data have suggested that FPF has multiple sub-lethal effects on individual honey bees. Our study aimed to expand the studies to the effects of field-realistic concentration of FPF. We found a statistically significant decrease in the survival rate of honey bees exposed to FPF, whereas there were no significantly negative effects on larvae development durations nor foraging activity. In addition, we found that the exposed foragers showed significantly higher expression of ApidNT, CYP9Q2, CYP9Q3, and AmInR-2 compared to the CK group (control group), but no alteration in the gene expression was observed in larvae. The exposed newly emerged bees showed significantly higher expression of Defensin and ApidNT. These results indicate that the chronic exposure to the field-realistic concentration of FPF has negligible effects, but more important synergistic and behavioral effects that can affect colony fitness should be explored in the future, considering the wide use of FPF on crops pollinated and visited by honey bees.
Selection and Validation of Suitable Reference Genes for RT-qPCR Analysis in the Rare Aquatic Firefly Aquatica leii (Coleoptera: Lampyridae)
Authors: Fu Xinhua , Meyer-Rochow Victor Benno
Published: April 2021

Aquatica leii Fu and Ballantyne is a species of rare aquatic firefly and endemic in China. It is considered good material to study the molecular mechanism of sexual flash communication systems. To improve conservation and behavioral research strategies, large-scale genetic studies involving gene-expression analysis are required and reverse transcription-quantitative polymerase chain reaction (RT-qPCR) is the most commonly used method. However, there have been very few reports on appropriate reference genes in any species of firefly. Here, we evaluated eight widely utilized reference genes including 18S, Actin, Reep5, Odc1, Tub, Gapdh, Ef1a and S27Ae for their expression stabilities in A. leii under three different conditions, i.e., life stage, tissue and dsRNA injection. Based on the gene stability ranking calculated by RefFinder, which integrates four algorithms (geNorm, delta Ct method, NormFinder, and BestKeeper), we recommend S27Ae and Reep5 as the most appropriate reference genes for molecular studies in different life stages; Ef1a and Odc1 for different tissues; Tub and Odc1 for RNAi studies. The most appropriate reference genes in all treatments are S27Ae and Tub. The results of this study will help improve accuracy and reliability to normalize RT-qPCR data in A. leii for further molecular analysis.
Ischemic Etiology and Prognosis in Men and Women with Acute Heart Failure
Authors: Vicent Lourdes , Guerra Jose , Vazquez-García Rafael , Gonzalez-Juanatey José R. , Dolz Luis Martínez , Segovia Javier , Pascual-Figal Domingo , Bover Ramón , Worner Fernando , Delgado Juan , Fernández-Avilés Francisco , Martínez-Sellés Manuel
Published: April 2021

Coronary heart disease is common in heart failure (HF). Our aim was to determine the impact of ischemic etiology on prognosis among men and women with HF. This study is a prospective national multicenter registry. The primary endpoint was 12-month mortality. Patients with HF and ischemic heart disease were stratified according to sex. A total of 1830 patients were enrolled of which 756 (41.3%) were women. Ischemic etiology was more common in men (446 (41.6%)) than in women (167 (22.2%)). Among patients with ischemic HF, diabetes was more frequent in women than in men. Ischemic etiology was not associated with higher mortality risk, and this was true for women (Hazard Ratio [HR] 1.51, 95% Confidence Interval [CI] 0.98–2.32; p = 0.61) and men (HR 1.14, 95% CI 0.81–1.61; p = 0.46), p-value for interaction: 0.067. Mortality/readmission risk in ischemic HF increased in men with previous readmissions (HR 1.15, 95% CI 1.02–1.29; p = 0.022), chronic obstructive pulmonary disease (HR1.20, 95% CI 1.02–1.41; p = 0.026) and in women with diabetes (HR 2.23, 95% CI 1.05–4.47; p = 0.035). Ischemic etiology was not associated with mortality in HF patients. In ischemic HF, the variables associated with a poor prognosis were diabetes in women and previous readmissions and chronic obstructive pulmonary disease in men.
Host Epigenetic Alterations and Hepatitis B Virus-Associated Hepatocellular Carcinoma
Authors: Zeisel Mirjam B. , Guerrieri Francesca , Levrero Massimo
Published: April 2021

Hepatocellular carcinoma (HCC) is the most frequent primary malignancy of the liver and a leading cause of cancer-related deaths worldwide. Although much progress has been made in HCC drug development in recent years, treatment options remain limited. The major cause of HCC is chronic hepatitis B virus (HBV) infection. Despite the existence of a vaccine, more than 250 million individuals are chronically infected by HBV. Current antiviral therapies can repress viral replication but to date there is no cure for chronic hepatitis B. Of note, inhibition of viral replication reduces but does not eliminate the risk of HCC development. HBV contributes to liver carcinogenesis by direct and indirect effects. This review summarizes the current knowledge of HBV-induced host epigenetic alterations and their association with HCC, with an emphasis on the interactions between HBV proteins and the host cell epigenetic machinery leading to modulation of gene expression.
Changes in the Composition and Function of Lipoproteins after Bariatric Surgery in Patients with Severe Obesity
Authors: Genua Idoia , Puig Núria , Miñambres Inka , Benítez Sonia , Gil Pedro , Grau-Agramunt Margarida , Rivas-Urbina Andrea , Balagué Carme , Fernández-Alanin Sonia , García-Osuna Álvaro , Pérez Antonio , Sánchez-Quesada José Luis
Published: April 2021

The effect of bariatric surgery on lipid profile and the qualitative characteristics of lipoproteins was analyzed in morbidly obese subjects. Thirteen obese patients underwent bariatric surgery. Plasma samples were obtained before surgery and at 6 and 12 months after the intervention. Thirteen healthy subjects comprised the control group. Lipid profile, hsCRP, and the composition and functional characteristics of VLDL, LDL, and HDL were assessed. At baseline, plasma from subjects with obesity had more triglycerides, VLDLc, and hsCRP, and less HDLc than the control group. These levels progressively normalized after surgery, although triglyceride and hsCRP levels remained higher than those in the controls. The main differences in lipoprotein composition between the obese subjects and the controls were increased apoE in VLDL, and decreased cholesterol and apoJ and increased apoC-III content in HDL. The pro-/anti-atherogenic properties of LDL and HDL were altered in the subjects with obesity at baseline compared with the controls, presenting smaller LDL particles that are more susceptible to modification and smaller HDL particles with decreased antioxidant capacity. Bariatric surgery normalized the composition of lipoproteins and improved the qualitative characteristics of LDL and HDL. In summary, patients with obesity present multiple alterations in the qualitative properties of lipoproteins compared with healthy subjects. Bariatric surgery reverted most of these alterations.
The Diagnostic Usefulness of Circulating Profile of Extracellular Matrix Components: Sulfated Glycosaminoglycans (sGAG), Hyaluronan (HA) and Extracellular Part of Syndecan-1 (sCD138) in Patients with Crohn’s Disease and Ulcerative Colitis
Authors: Derkacz Alicja , Olczyk Paweł , Jura-Półtorak Agnieszka , Olczyk Krystyna , Komosinska-Vassev Katarzyna
Published: April 2021

The described research focused on the diagnostic usefulness of sulfated glycosaminoglycans (sGAG), hyaluronan (HA), and extracellular part of syndecan-1 (sCD138) as new markers related to extracellular matrix (ECM) remodeling in the intestine during the two most common forms of inflammatory bowel diseases (IBD), i.e., ulcerative colitis (UC) and Crohn’ disease (CD). Inflammatory markers belonging to ECM components were assessed in serum of patients with IBD using an immunoenzymatic method (HA and sCD138) and a method based on the reaction with dimethylmethylene blue (sulfated GAG). Measurements were carried out twice: at baseline and after one year of therapy with prednisone (patients with CD) or adalimumab (patients with UC). No quantitative changes were observed in serum sGAG, HA, and sCD138 concentrations between patients newly diagnosed with CD and the healthy group. In the case of patients with UC, the parameter which significantly differentiated healthy subjects and patients with IBD before biological therapy was HA. Significant correlation between serum HA level and inflammation activity, expressed as Mayo score, was also observed in patients with UC. Moreover, the obtained results have confirmed that steroid therapy with prednisone significantly influenced the circulating profile of all examined ECM components (sGAG, HA, and sCD138), whereas adalimumab therapy in patients with UC led to a significant change in only circulating sGAG levels. Moreover, the significant differences in serum HA levels between patients with UC and CD indicate that quantification of circulating HA may be useful in the differential diagnosis of CD and UC.
Urinary Biomarkers for Early Diagnosis of Lung Cancer
Authors: Gasparri Roberto , Sedda Giulia , Caminiti Valentina , Maisonneuve Patrick , Prisciandaro Elena , Spaggiari Lorenzo
Published: April 2021

Lung cancer is the leading cause of cancer deaths worldwide. Its early detection has the potential to significantly impact the burden of the disease. The screening and diagnostic techniques in current use suffer from limited specificity. The need therefore arises for a reliable biomarker to identify the disease earlier, which can be integrated into a test. This test would also allow for the recurrence risk after surgery to be stratified. In this context, urine could represent a non-invasive alternative matrix, with the urinary metabolomic profile offering a potential source for the discovery of diagnostic biomarkers. This paper aims to examine the current state of research and the potential for translation into clinical practice.
Utility of Transient Elastography for the Screening of Liver Disease in Patients with Alpha1-Antitrypsin Deficiency
Authors: Pons Mònica , Núñez Alexa , Esquinas Cristina , Torres-Durán María , Rodríguez-Hermosa Juan , Calle Myriam , Tubio-Pérez Ramón , Belmonte Irene , Rodríguez-Frías Francisco , Rodríguez Esther , Genescà Joan , Miravitlles Marc , Barrecheguren Miriam
Published: April 2021

Screening of liver disease in alpha-1 antitrypsin deficiency (AATD) is usually carried out with liver enzymes, with low sensitivity. We conducted a multicenter cross-sectional study aiming to describe the utility of transient elastography for the identification of liver disease in patients with AATD. A total of 148 AATD patients were included. Among these, 54.7% were Pi*ZZ and 45.3% were heterozygous for the Z allele. Between 4.9% and 16.5% of patients had abnormal liver enzymes, without differences among genotypes. Liver stiffness measurement (LSM) was significantly higher in Pi*ZZ individuals than in heterozygous Z (5.6 vs. 4.6 kPa; p = 0.001). In total, in 8 (5%) individuals LSM was >7.5 kPa, considered significant liver fibrosis, and ≥10 kPa in 3 (1.9%) all being Pi*ZZ. Elevated liver enzymes were more frequently observed in patients with LSM > 7.5 kPa, but in 5 out of 8 of these patients all liver enzymes were within normal range. In patients with AATD, the presence of abnormal liver enzymes is frequent; however, most of these patients do not present significant liver fibrosis. Transient elastography can help to identify patients with liver fibrosis even with normal liver enzymes and should be performed in all Z-allele carriers to screen for liver disease.
Effectiveness of Equine-Assisted Activities and Therapies for Improving Adaptive Behavior and Motor Function in Autism Spectrum Disorder
Authors: Zoccante Leonardo , Marconi Michele , Ciceri Marco Luigi , Gagliardoni Silvia , Gozzi Luigi Alberto , Sabaini Sara , Di Gennaro Gianfranco , Colizzi Marco
Published: April 2021

Equine-assisted activities and therapies (EAAT) have been suggested to improve adaptive behavior, and possibly motor function, in autism spectrum disorder (ASD). This study investigated the effects of EAAT on adaptive behavior and motor function in 15 children with ASD (13 males) aged 7–15 years as well as the impact of EAAT on the magnitude of stress in the parent–child system and the evolution in the child interaction with both the trained therapist and the therapeutic animal through the 20 weekly sessions of EAAT. EAAT were associated with greater adaptive behavior and coordination (all p ≤ 0.01) as well as a progressive improvement in the child’s abilities to respond to the increasing complexity of such form of positive behavioral support (all p < 0.001). However, EAAT did not prove to be effective in reducing parental distress. Collectively, preliminary evidence presented here may have important public health implications and gives reason to hope that EAAT could possibly be an effective option in ASD, warranting further investigation of its potential benefits in clinical trials among larger samples.
Risk Factor Analysis for Infection after Medial Open Wedge High Tibial Osteotomy
Authors: Liu Ta-Wei , Chiu Chih-Hao , Chen Alvin Chao-Yu , Chang Shih-Sheng , Chan Yi-Sheng
Published: April 2021

Background: Medial open wedge high tibial osteotomy (MOWHTO) is a well-established treatment for osteoarthritis of the medial tibiofemoral compartment. Surgical site infection (SSI) after MOWHTO is a devastating complication that may require further surgery. In this study, we aimed to identify the risk factors for infection after MOWHTO over 1 to 4 years of follow-up. Methods: Fifty-nine patients who underwent MOWHTO combined with knee arthroscopic surgery were included in this prospective study. Artificial bone grafts were used in all cases. Possible risk factors, including sex, age, body mass index (BMI), underlying disease, hospitalization length, correction angle, and surgery time, were recorded. Both univariate and multivariate analysis were used. Results: A total of 59 patients who underwent 61 operations were included. Eleven patients (18.0%) were reported to have SSI. Univariate analysis showed that smoking and diabetes mellitus were positively associated with SSI. Multivariate analysis showed that smoking and age were positively associated with SSI. Three patients (4.9%) were reported to suffer from deep SSI, requiring surgical debridement, all of whom were male smokers. Conclusion: Smoking, diabetes mellitus, and old age were identified to be possible risk factors of SSI after MOWHTO. These findings are common risk factors of SSI after orthopedic surgery according to the literature. Patient selection should be performed cautiously, and postoperative prognosis for MOWHTO should be carefully explained to patients who smoke.
Mechanistic Insight into Orthodontic Tooth Movement Based on Animal Studies: A Critical Review
Authors: Jeon Hyeran Helen , Teixeira Hellen , Tsai Andrew
Published: April 2021

Alveolar bone remodeling in orthodontic tooth movement (OTM) is a highly regulated process that coordinates bone resorption by osteoclasts and new bone formation by osteoblasts. Mechanisms involved in OTM include mechano-sensing, sterile inflammation-mediated osteoclastogenesis on the compression side and tensile force-induced osteogenesis on the tension side. Several intracellular signaling pathways and mechanosensors including the cilia and ion channels transduce mechanical force into biochemical signals that stimulate formation of osteoclasts or osteoblasts. To date, many studies were performed in vitro or using human gingival crevicular fluid samples. Thus, the use of transgenic animals is very helpful in examining a cause and effect relationship. Key cell types that participate in mediating the response to OTM include periodontal ligament fibroblasts, mesenchymal stem cells, osteoblasts, osteocytes, and osteoclasts. Intercellular signals that stimulate cellular processes needed for orthodontic tooth movement include receptor activator of nuclear factor-κB ligand (RANKL), tumor necrosis factor-α (TNF-α), dickkopf Wnt signaling pathway inhibitor 1 (DKK1), sclerostin, transforming growth factor beta (TGF-β), and bone morphogenetic proteins (BMPs). In this review, we critically summarize the current OTM studies using transgenic animal models in order to provide mechanistic insight into the cellular events and the molecular regulation of OTM.
Methodological Aspects of Randomized Controlled Trials for Tinnitus: A Systematic Review and How a Decision Support System Could Overcome Barriers
Authors: Kikidis Dimitrios , Vassou Evgenia , Schlee Winfried , Iliadou Eleftheria , Markatos Nikolaos , Triantafyllou Aikaterini , Langguth Berthold
Published: April 2021

Although a wide range of tinnitus management interventions is currently under research and a variety of therapeutic interventions have already been applied in clinical practice, no optimal and universal tinnitus treatment has been reached yet. This fact is to some extent a consequence of the high heterogeneity of the methodologies used in tinnitus related clinical studies. In this manuscript, we have identified, summarized, and critically appraised tinnitus-related randomized clinical trials since 2010, aiming at systematically mapping the research conducted in this area. The results of our analysis of the 73 included randomized clinical trials provide important insight on the identification of limitations of previous works, methodological pitfalls or gaps in current knowledge, a prerequisite for the adequate interpretation of current literature and execution of future studies.
Circulating MicroRNA: Incident Asthma Prediction and Vitamin D Effect Modification
Authors: Li Jiang , Tiwari Anshul , Mirzakhani Hooman , Wang Alberta L. , Kho Alvin T. , McGeachie Michael J. , Litonjua Augusto A. , Weiss Scott T. , Tantisira Kelan G.
Published: April 2021

Of children with recurrent wheezing in early childhood, approximately half go on to develop asthma. MicroRNAs have been described as excellent non-invasive biomarkers due to their prognostic utility. We hypothesized that circulating microRNAs can predict incident asthma and that that prediction might be modified by vitamin D. We selected 75 participants with recurrent wheezing at 3 years old from the Vitamin D Antenatal Asthma Reduction Trial (VDAART). Plasma samples were collected at age 3 and sequenced for small RNA-Seq. The read counts were normalized and filtered by depth and coverage. Logistic regression was employed to associate miRNAs at age 3 with asthma status at age 5. While the overall effect of miRNA on asthma occurrence was weak, we identified 38 miRNAs with a significant interaction effect with vitamin D and 32 miRNAs with a significant main effect in the high vitamin D treatment group in VDAART. We validated the VDAART results in Project Viva for both the main effect and interaction effect. Meta-analysis was performed on both cohorts to obtain the combined effect and a logistic regression model was used to predict incident asthma at age 7 in Project Viva. Of the 23 overlapped miRNAs in the stratified and interaction analysis above, 9 miRNAs were replicated in Project Viva with strong effect size and remained in the meta-analysis of the two populations. The target genes of the 9 miRNAs were enriched for asthma-related Kyoto Encyclopedia of Genes and Genomes (KEGG) signaling pathways. Using logistic regression, microRNA hsa-miR-574-5p had a good prognostic ability for incident asthma prognosis with an area under the receiver operating characteristic (AUROC) of 0.83. In conclusion, miRNAs appear to be good biomarkers of incident asthma, but only when vitamin D level is considered.
Hypoxia Transcriptomic Modifications Induced by Proton Irradiation in U87 Glioblastoma Multiforme Cell Line
Authors: Bravatà Valentina , Tinganelli Walter , Cammarata Francesco P. , Minafra Luigi , Calvaruso Marco , Sokol Olga , Petringa Giada , Cirrone Giuseppe A.P. , Scifoni Emanuele , Forte Giusi I. , Russo Giorgio
Published: April 2021

In Glioblastoma Multiforme (GBM), hypoxia is associated with radioresistance and poor prognosis. Since standard GBM treatments are not always effective, new strategies are needed to overcome resistance to therapeutic treatments, including radiotherapy (RT). Our study aims to shed light on the biomarker network involved in a hypoxic (0.2% oxygen) GBM cell line that is radioresistant after proton therapy (PT). For cultivating cells in acute hypoxia, GSI’s hypoxic chambers were used. Cells were irradiated in the middle of a spread-out Bragg peak with increasing PT doses to verify the greater radioresistance in hypoxic conditions. Whole-genome cDNA microarray gene expression analyses were performed for samples treated with 2 and 10 Gy to highlight biological processes activated in GBM following PT in the hypoxic condition. We describe cell survival response and significant deregulated pathways responsible for the cell death/survival balance and gene signatures linked to the PT/hypoxia configurations assayed. Highlighting the molecular pathways involved in GBM resistance following hypoxia and ionizing radiation (IR), this work could suggest new molecular targets, allowing the development of targeted drugs to be suggested in association with PT.
Rifaximin as a Potential Treatment for IgA Nephropathy in a Humanized Mice Model
Authors: Di Leo Vincenzo , Gleeson Patrick J. , Sallustio Fabio , Bounaix Carine , Da Silva Jennifer , Loreto Gesualdo , Ben Mkaddem Sanae , Monteiro Renato C.
Published: April 2021

IgA Nephropathy (IgAN) is the most common glomerulonephritis worldwide, characterized by the mesangial deposition of abnormally glycosylated IgA1 (Gd-IgA). The production of Gd-IgA occurs in mucose-associated lymphoid tissue (MALT). The microbiota plays a role in MALT modulation. Rifaximin (NORMIX®), a non-absorbable oral antibiotic, induces positive modulation of the gut microbiota, favoring the growth of bacteria beneficial to the host. Here, we evaluate the effect of rifaximin on a humanized mice model of IgAN (α1KI-CD89Tg). Methods: The α1KI-CD89Tg mice were treated by the vehicle (olive oil) or rifaximin (NORMIX®). Serum levels of hIgA, hIgA1–sCD89, and mIgG–hIgA1 immune complexes were determined. Glomerular hIgA1 deposit and CD11b+ cells recruitment were revealed using confocal microscopy. Furthermore, the mRNA of the B-Cell Activating Factor (BAFF), polymeric immunoglobulin receptor (pIgR), and Tumor Necrosing Factor-α (TNF-α) in gut samples were detected by qPCR. Results: Rifaximin treatment decreased the urinary protein-to-creatinine ratio, serum levels of hIgA1–sCD89 and mIgG–hIgA1 complexes, hIgA1 glomerular deposition, and CD11b+ cell infiltration. Moreover, rifaximin treatment decreased significantly BAFF, pIgR, and TNF-α mRNA expression. Conclusions: Rifaximin decreased the IgAN symptoms observed in α1KI-CD89Tg mice, suggesting a possible role for it in the treatment of the disease.
Challenges of Prevention for a Sustainable Personalized Medicine
Authors: Pastorino Roberta , Loreti Claudia , Giovannini Silvia , Ricciardi Walter , Padua Luca , Boccia Stefania
Published: April 2021

The development and implementation of the approaches of personalized medicine for disease prevention are still at infancy, although preventive activities in healthcare represent a key pillar to guarantee health system sustainability. There is an increasing interest in finding informative markers that indicate the disease risk before the manifestation of the disease (primary prevention) or for early disease detection (secondary prevention). Recently, the systematic collection and study of clinical phenotypes and biomarkers consented to the advance of Rehabilomics in tertiary prevention. It consents to identify relevant molecular and physiological factors that can be linked to plasticity, treatment response, and natural recovery. Implementation of these approaches would open avenues to identify people at high risk and enable new preventive lifestyle interventions or early treatments targeted to their individual genomic profile, personalizing prevention and rehabilitation. The integration of personalized medicine into prevention may benefit citizens, patients, healthcare professionals, healthcare authorities, and industry, and ultimately will seek to contribute to better health and quality of life for Europe’s citizens.
Changes in Land-Use and Ecosystem Service Value in Guangdong Province, Southern China, from 1990 to 2018
Authors: Ye Yanqiong , Zhang Jiaen , Wang Ting , Bai Hui , Wang Xuan , Zhao Wei
Published: April 2021

Land-use/cover is one of the major factors that affect the ecosystem and the services it provides. The impact of land-use change on ecosystem service value is a hotspot in developing countries, especially China—a region with rapid economic development and rapid population growth. As the leading area of China’s reform and opening-up, Guangdong province in southern China is subjected to land-use conversion that significantly alters the capacity of natural ecosystem to provide ecosystem services supporting human well-being. We analyzed the characteristics of land-use changes from 1990 to 2018 using the four-phase land-use data interpreted from Landsat satellite images. We estimated the ecosystem service value through a well-established benefit transfer method using modified local value coefficients, analyzed the trade-offs and synergies among ecosystem services through ecosystem service trade-off degree, and compared the relationship between ecosystem services value, economic development, and population in Guangdong province. The results indicated that the following: (1) Built-Up Area drastically expanded from 6783.1 km2 in 1990 to 13,142.0 km2 in 2018 (93.7%), especially in the Pearl River Delta, where the growth rate of Built-Up Area expansion was up to 169.0%. The other land-use types were all contracted as Cropland (−10.9%), Forestland (−1.0%), Grassland (−4.0%), Water Body (−2.1%), and Unused Land (−24.4%). (2) Total ecosystem service value decreased from US$121,666 billion in 1990 to US$116,432 billion in 2018 (−4.3%). Cropland, Forestland, and Water Body played the most important roles for the total ecosystem service value. Water supply experienced the largest declines in ecosystem services value (US$ −1866.3 million, −10.1%), followed by waste treatment (7.6%) and gas regulation (−4.9%). (3) Synergy was the dominant relationship among ecosystem services. The above results can not only serve as reference case for other provinces/regions/countries/ to carry out relevant research work but also provide much focus on land-use planning to manage the impacts of land-use change on regional ecosystem services function.