bluuebunny/crossref_metadata_2025 huggingface dataset:
Galectin-2 Has Bactericidal Effects against Helicobacter pylori in a β-galactoside-Dependent Manner
Authors: Sasaki Takaharu , Saito Rei , Oyama Midori , Takeuchi Tomoharu , Tanaka Toru , Natsume Hideshi , Tamura Mayumi , Arata Yoichiro , Hatanaka Tomomi
Published: April 2020

Helicobacter pylori is associated with the onset of gastritis, peptic ulcers, and gastric cancer. Galectins are a family of β-galactoside-binding proteins involved in diverse biological phenomena. Galectin-2 (Gal-2), a member of the galectin family, is predominantly expressed in the gastrointestinal tract. Although some galectin family proteins are involved in immunoreaction, the role of Gal-2 against H. pylori infection remains unclear. In this study, the effects of Gal-2 on H. pylori morphology and survival were examined. Gal-2 induced H. pylori aggregation depending on β-galactoside and demonstrated a bactericidal effect. Immunohistochemical staining of the gastric tissue indicated that Gal-2 existed in the gastric mucus, as well as mucosa. These results suggested that Gal-2 plays a role in innate immunity against H. pylori infection in gastric mucus.
Auditory Neuropathy Spectrum Disorders: From Diagnosis to Treatment: Literature Review and Case Reports
Authors: De Siati Romolo Daniele , Rosenzweig Flora , Gersdorff Guillaume , Gregoire Anaïs , Rombaux Philippe , Deggouj Naïma
Published: April 2020

Auditory neuropathy spectrum disorder (ANSD) refers to a range of hearing impairments characterized by deteriorated speech perception, despite relatively preserved pure-tone detection thresholds. Affected individuals usually present with abnormal auditory brainstem responses (ABRs), but normal otoacoustic emissions (OAEs). These electrophysiological characteristics have led to the hypothesis that ANSD may be caused by various dysfunctions at the cochlear inner hair cell (IHC) and spiral ganglion neuron (SGN) levels, while the activity of outer hair cells (OHCs) is preserved, resulting in discrepancies between pure-tone and speech comprehension thresholds. The exact prevalence of ANSD remains unknown; clinical findings show a large variability among subjects with hearing impairment ranging from mild to profound hearing loss. A wide range of prenatal and postnatal etiologies have been proposed. The study of genetics and of the implicated sites of lesion correlated with clinical findings have also led to a better understanding of the molecular mechanisms underlying the various forms of ANSD, and may guide clinicians in better screening, assessment and treatment of ANSD patients. Besides OAEs and ABRs, audiological assessment includes stapedial reflex measurements, supraliminal psychoacoustic tests, electrocochleography (ECochG), auditory steady-state responses (ASSRs) and cortical auditory evoked potentials (CAEPs). Hearing aids are indicated in the treatment of ANSD with mild to moderate hearing loss, whereas cochlear implantation is the first choice of treatment in case of profound hearing loss, especially in case of IHC presynaptic disorders, or in case of poor auditory outcomes with conventional hearing aids.
Transcranial Direct Current Stimulation of the Occipital Cortex in Medication Overuse Headache: A Pilot Randomized Controlled Cross-Over Study
Authors: Mansour Anthony G. , Ahdab Rechdi , Khazen Georges , El-Khoury Christelle , Sabbouh Toni M. , Salem Maher , Yamak Wissam , Chalah Moussa A. , Ayache Samar S. , Riachi Naji
Published: April 2020

Background: Medication overuse headache (MOH) is a chronic pain syndrome that arises from the frequent use of acute antimigraine drugs. Transcranial direct current stimulation (tDCS) is a non-invasive brain stimulation technique with a possible therapeutic effect in this particular context. Methods: This was a randomized, sham-controlled, cross-over study. Eighteen patients with MOH (17 women, age range: 20–38 years) received three sets of three consecutive daily sessions of tDCS: anodal tDCS over the prefrontal cortex, cathodal tDCS over the occipital cortex ipsilateral to the dominant side of migraine pain, and sham. The order in which the tDCS blocks were delivered was randomly defined based on a 1:1:1 ratio. Patients filled in a migraine diary that allowed recording of the pain intensity (visual analogue scale) and the daily consumption of analgesic pills from one week before to two weeks after each condition. Results: Both prefrontal and occipital tDCS lowered the total number of migraine days and the number of severe migraine days per week at week 1, but only the effects of occipital tDCS on these two outcomes lasted until week 2. Only occipital tDCS decreased the daily analgesic pills consumption, at weeks 1 and 2. Conclusion: Three consecutive days of cathodal occipital tDCS appear to improve the clinical outcomes in patients with MOH.
Prognostic Value of Non-Contrast CT Markers and Spot Sign for Outcome Prediction in Patients with Intracerebral Hemorrhage under Oral Anticoagulation
Authors: Zimmer Sebastian , Meier Jörn , Minnerup Jens , Wildgruber Moritz , Broocks Gabriel , Nawabi Jawed , Morotti Andrea , Kemmling Andre , Psychogios Marios , Hanning Uta , Sporns Peter B.
Published: April 2020

Introduction: In patients with spontaneous intracerebral hemorrhage (ICH), several non-contrast computed tomography (NCCT) markers and the spot sign (SS) in computed tomography (CT) angiography (CTA) have been established for the prediction of hematoma growth and neurological outcome. However, the prognostic value of these markers in patients under oral anticoagulation (ORAC) is unclear. We hypothesized that outcome prediction by these imaging markers may be significantly different between patients with and without ORAC. Therefore, we aimed to investigate the predictive value of NCCT markers and SS in patients with ICH under ORAC. Methods: This is a retrospective study of the database for patients with ICH at a German tertiary stroke center. Inclusion criteria were (1) patients with ICH, (2) oral anticoagulation within the therapeutic range, and (3) NCCT and CTA performed on admission within 6 h after onset of symptoms. We defined a binary outcome: modified Rankin Scale (mRS) ≤ 3 = good outcome versus mRS > 3 = poor outcome at discharge. The predictive value of each sign was assessed in uni- and multivariable logistic regression models. Results: Of 129 patients with ICH under ORAC, 76 (58.9%) presented with hypodensities within the hematoma in admission NCCT, 64 (52.7%) presented with an irregular shape of the hematoma, 60 (46.5%) presented with a swirl sign, 49 (38.0%) presented with a black hole sign, and 46 (35.7%) presented with a heterogeneous density of the hematoma. Moreover, 44 (34.1%) patients had a satellite sign, in 20 (15.5%) patients, an island sign was detected, 18 (14.0%) patients were blend-sign positive, and 14 (10.9%) patients presented with a CTA spot sign. Inter-rater agreement was very high for all included characteristics between the two readers. Multivariable logistic regression analysis identified the presence of black hole sign (odds ratio 10.59; p < 0.001), swirl sign (odds ratio 14.06; p < 0.001), and satellite sign (odds ratio 6.38; p = 0.011) as independent predictors of poor outcome. Conclusions: The distribution and prognostic value of several NCCT markers and CTA spot sign in ICH patients under ORAC is comparable to those with spontaneous ICH, even though these parameters are partly based on coagulant status. These findings suggest that a similar approach can be used for further research regarding outcome prediction in ICH patients under ORAC and those with spontaneous ICH.
Treatment of Rheumatoid Arthritis-Associated Interstitial Lung Disease: Lights and Shadows
Authors: Cassone Giulia , Manfredi Andreina , Vacchi Caterina , Luppi Fabrizio , Coppi Francesca , Salvarani Carlo , Sebastiani Marco
Published: April 2020

Rheumatoid arthritis (RA) is a chronic and systemic inflammatory disease affecting 0.5–1% of the population worldwide. Interstitial lung disease (ILD) is a serious pulmonary complication of RA and it is responsible for 10–20% of mortality, with a mean survival of 5–8 years. However, nowadays there are no therapeutic recommendations for the treatment of RA-ILD. Therapeutic options for RA-ILD are complicated by the possible pulmonary toxicity of many disease modifying anti-rheumatic drugs (DMARDs) and by their unclear efficacy on pulmonary disease. Therefore, joint and lung involvement should be evaluated independently of each other for treatment purposes. On the other hand, some similarities between RA-ILD and idiopathic pulmonary fibrosis and the results of the recent INBIULD trial suggest a possible future role for antifibrotic agents. From this perspective, we review the current literature describing the pulmonary effects of drugs (immunosuppressants, conventional, biological and target synthetic DMARDs and antifibrotic agents) in patients with RA and ILD. In addition, we suggest a framework for the management of RA-ILD patients and outline a research agenda to fill the gaps in knowledge about this challenging patient cohort.
A New System for Assessing Visual Disability Using a Digital Visor
Authors: Sangiuolo Raffaele , Amore Filippo , Bacci Mauro , Brusini Paolo , Cruciani Filippo , Gualtieri Giacomo , Lancia Massimo , Sangiuolo Giulia , Sangiuolo Mario
Published: April 2020

Background: Considering the lack of universally accepted visual requirements for driving and for defining various grades of visual disability, the aim of this study is to propose a new method that provides a numerical score resulting from a combined assessment of the visual field and visual acuity loss obtained using a digital technology visor. Methods: This study presents a new system for calculating the percentage of visual disability by combining binocular visual acuity and binocular visual field assessments. A new Global Vision Evaluation System digital technology visor uses standardized, reproducible criteria to produce well-defined, numerically expressed test results. Through a specific algorithm, the device produces a numerical value expressing the percentage of visual disability. Results: Eighty-six subjects with various types of visual impairment underwent visual acuity and visual field test examinations carried out employing both traditional methods and the new digital visor. The two methods provided homogeneously similar results regarding the positioning of the subjects on the visual disability scale. Conclusions: The new digital visor seems to be a valid method to ensure that visual disability assessments are more homogeneous and reliable, and that, consequently, the resources available for this purpose are more fairly distributed.
Long-Term Redistribution of Peripheral Lymphocyte Subpopulations after Switching from Calcineurin to mTOR Inhibitors in Kidney Transplant Recipients
Authors: Llinàs-Mallol Laura , Redondo-Pachón Dolores , Raïch-Regué Dàlia , Pérez-Sáez María José , Yélamos José , Duran Xavier , Faura Anna , López-Botet Miguel , Pascual Julio , Crespo Marta
Published: April 2020

Classical immunosuppression based on steroids, calcineurin inhibitors, and mycophenolate results in several unwanted effects and unsatisfactory long-term outcomes in kidney transplantation (KT). New immunosuppressors search for fewer adverse events and increased graft survival but may have a distinct impact on graft function and immunological biomarkers according to their mechanism of action. This prospective study evaluates the immunological effect of tacrolimus to serine/threonine protein kinase mechanistic target of rapamycin inhibitors (mTORi) conversion in 29 KT recipients compared with 16 controls maintained on tacrolimus. We evaluated renal function, human leukocyte antigen (HLA) antibodies and peripheral blood lymphocyte subsets at inclusion and at 3, 12, and 24 months later. Twenty immunophenotyped healthy subjects served as reference. Renal function remained stable in both groups with no significant change in proteinuria. Two patients in the mTORi group developed HLA donor-specific antibodies and none in the control group (7% vs. 0%, p = 0.53). Both groups showed a progressive increase in regulatory T cells, more prominent in patients converted to mTORi within the first 18 months post-KT (p < 0.001). All patients showed a decrease in naïve B cells (p < 0.001), excepting those converted to mTORi without receiving steroids (p = 0.31). Transitional B cells significantly decreased in mTORi patients (p < 0.001), independently of concomitant steroid treatment. Finally, CD56bright and CD94/NK group 2 member A receptor positive (NKG2A+) Natural Killer (NK) cell subsets increased in mTORi- compared to tacrolimus-treated patients (both p < 0.001). Patients switched to mTORi displayed a significant redistribution of peripheral blood lymphocyte subpopulations proposed to be associated with graft outcomes. The administration of steroids modified some of these changes.
Association of HSV-1 and Reduced Oral Bacteriota Diversity with Chemotherapy-Induced Oral Mucositis in Patients Undergoing Autologous Hematopoietic Stem Cell Transplantation
Authors: Lee Ahreum , Hong Junshik , Shin Dong-Yeop , Koh Youngil , Yoon Sung-Soo , Kim Pil-Jong , Kim Hong-Gee , Kim Inho , Park Hee-Kyung , Choi Youngnim
Published: April 2020

Oral mucositis (OM) is a common complication of chemotherapy and remains a significant unmet need. The aim of this study was to investigate the role of oral bacteriota and HSV-1 in OM. Forty-six patients admitted for autologous hematopoietic stem cell transplantation were longitudinally evaluated for OM, Candida, HSV-1, and leukocyte count, and buccal mucosal bacterial samples were obtained during their admission period. The bacterial communities collected at the baseline and post-chemotherapy, chosen from the time with the highest severity, were analyzed by sequencing the 16S rRNA gene. Twenty (43.5%) patients developed OM, the severity of which ranged from 1 to 5 according to the Oral Mucositis Assessment Scale (OMAS). Chemotherapy significantly increased the prevalence of HSV-1 detection but not that of Candida. The bacterial communities of patients after conditioning chemotherapy were characterized by aberrant enrichment of minor species and decreased evenness and Shannon diversity. After adjustment for age, gender, and neutropenia, the presence of HSV-1 was associated with the incidence of OM (odds ratio = 3.668, p = 0.004), while the decrease in Shannon diversity was associated with the severity of OM (β = 0.533 ± 0.220, p = 0.015). The control of HSV-1 and restoration of oral bacterial diversity may be a novel option to treat or prevent OM.
The Clinical Role of Insulin Degludec/Insulin Aspart in Type 2 Diabetes: An Empirical Perspective from Experience in Australia
Authors: Glastras Sarah J. , Cohen Neale , Dover Thomas , Kilov Gary , MacIsaac Richard J. , McGill Margaret , Fulcher Greg R.
Published: April 2020

Treatment intensification in people with type 2 diabetes following failure of basal insulin commonly involves the addition of a rapid-acting insulin analogue (basal plus one or more prandial doses; multiple daily injections) or by a switch to premixed insulin. Insulin degludec/insulin aspart (IDegAsp), comprising rapid-acting insulin aspart and ultra-long-acting insulin degludec in solution, enables both fasting and post-prandial glucose control, with some advantages over other treatment intensification options. These include straightforward dose titration, flexibility in dose timing, low injection burden, simplicity of switching and a lower risk of hypoglycaemia. In Australia, where insulin degludec on its own is not available, IDegAsp enables patients to still benefit from its ultra-long-acting properties. This review aims to provide guidance on where and how to use IDegAsp. Specifically, guidance is included on the initiation of IDegAsp in insulin-naïve patients, treatment intensification from basal insulin, switching from premixed or basal-bolus insulin to IDegAsp, up-titration from once- to twice-daily IDegAsp and the use of IDegAsp in special populations or situations.
Vessel Density and Vessel Tortuosity Quantitative Analysis of Arteritic and Non-arteritic Anterior Ischemic Optic Neuropathies: An Optical Coherence Tomography Angiography Study
Authors: Pierro Luisa , Arrigo Alessandro , Aragona Emanuela , Cavalleri Michele , Bandello Francesco
Published: April 2020

The aim of this study was to perform quantitative optical coherence tomography angiography (OCTA) assessment of arteritic and non-arteritic anterior ischemic optic neuropathies (AION; NAION). The study was designed as an observational, cross-sectional case series. All patients underwent complete ophthalmologic evaluation including LogMAR best-corrected visual acuity (BCVA), structural optical coherence tomography (OCT) and OCTA images, and dye-based angiography. Retinal nerve fiber layer (RNFL) thickness was obtained from structural OCT, and vessel density (VD) and vessel tortuosity (VT) were measured for each optic nerve head vascular plexus. After selecting the quadrants showing visual field defects, measured by Humphrey 30.2 perimetry (Zeiss Meditec, Dublin, CA, USA), we assessed the correlation between the localization of visual field defects and the quadrants showing impairments of RNFL, VD, and VT. Thirty naïve AION patients (15 arteritic AION (AAION) and 15 non-arteritic AION (NAION)) were included. LogMAR BCVA was 0.6 ± 0.2 for AAION and 0.3 ± 0.3 for NAION (p < 0.01). AAION and NAION eyes showed significant differences in terms of visual field involvement as well as VD and VT values, with remarkably worse alterations affecting AAION eyes. VD values perfectly matched with the quadrants showing RNFL and visual field defects. On the contrary, VT resulted remarkably decreased in all the quadrants, with even worse values in the quadrants showing RNFL and visual field alterations. The present study showed that AAION eyes are more injured than NAION ones. VD represents a good parameter for the detection of the main site on vascular impairment. Remarkably, VT resulted in a more sensitive parameter for the quantitative detection of blood flow impairment in AION disease.
Inositol 1,4,5-Trisphosphate Receptors in Human Disease: A Comprehensive Update
Authors: Gambardella Jessica , Lombardi Angela , Morelli Marco Bruno , Ferrara John , Santulli Gaetano
Published: April 2020

Inositol 1,4,5-trisphosphate receptors (ITPRs) are intracellular calcium release channels located on the endoplasmic reticulum of virtually every cell. Herein, we are reporting an updated systematic summary of the current knowledge on the functional role of ITPRs in human disorders. Specifically, we are describing the involvement of its loss-of-function and gain-of-function mutations in the pathogenesis of neurological, immunological, cardiovascular, and neoplastic human disease. Recent results from genome-wide association studies are also discussed.
Human Wharton’s Jelly—Cellular Specificity, Stemness Potency, Animal Models, and Current Application in Human Clinical Trials
Authors: Stefańska Katarzyna , Ożegowska Katarzyna , Hutchings Greg , Popis Małgorzata , Moncrieff Lisa , Dompe Claudia , Janowicz Krzysztof , Pieńkowski Wojciech , Gutaj Paweł , Shibli Jamil , Prado Walterson , Piotrowska-Kempisty Hanna , Mozdziak Paul , Bruska Małgorzata , Zabel Maciej , Kempisty Bartosz , Nowicki Michał
Published: April 2020

Stem cell therapies offer a great promise for regenerative and reconstructive medicine, due to their self-renewal and differentiation capacity. Although embryonic stem cells are pluripotent, their utilization involves embryo destruction and is ethically controversial. Therefore, adult tissues that have emerged as an alternative source of stem cells and perinatal tissues, such as the umbilical cord, appear to be particularly attractive. Wharton’s jelly, a gelatinous connective tissue contained in the umbilical cord, is abundant in mesenchymal stem cells (MSCs) that express CD105, CD73, CD90, Oct-4, Sox-2, and Nanog among others, and have the ability to differentiate into osteogenic, adipogenic, chondrogenic, and other lineages. Moreover, Wharton’s jelly-derived MSCs (WJ-MSCs) do not express MHC-II and exhibit immunomodulatory properties, which makes them a good alternative for allogeneic and xenogeneic transplantations in cellular therapies. Therefore, umbilical cord, especially Wharton’s jelly, is a promising source of mesenchymal stem cells.
Diagnostics, Risk Factors, Treatment and Outcomes of Acute Kidney Injury in a New Paradigm
Authors: Thongprayoon Charat , Hansrivijit Panupong , Kovvuru Karthik , Kanduri Swetha R. , Torres-Ortiz Aldo , Acharya Prakrati , Gonzalez-Suarez Maria L. , Kaewput Wisit , Bathini Tarun , Cheungpasitporn Wisit
Published: April 2020

Acute kidney injury (AKI) is a common clinical condition among patients admitted in the hospitals. The condition is associated with both increased short-term and long-term mortality. With the development of a standardized definition for AKI and the acknowledgment of the impact of AKI on patient outcomes, there has been increased recognition of AKI. Two advances from past decades, the usage of computer decision support and the discovery of AKI biomarkers, have the ability to advance the diagnostic method to and further management of AKI. The increasingly widespread use of electronic health records across hospitals has substantially increased the amount of data available to investigators and has shown promise in advancing AKI research. In addition, progress in the finding and validation of different forms of biomarkers of AKI within diversified clinical environments and has provided information and insight on testing, etiology and further prognosis of AKI, leading to future of precision and personalized approach to AKI management. In this this article, we discussed the changing paradigms in AKI: From mechanisms to diagnostics, risk factors, and management of AKI.
Galectin-3 is Associated with Cardiovascular Events in Post-Acute Coronary Syndrome Patients with Type-2 Diabetes
Authors: Lorenzo-Almorós Ana , Pello Ana , Aceña Álvaro , Martínez-Milla Juan , González-Lorenzo Óscar , Tarín Nieves , Cristóbal Carmen , Blanco-Colio Luis M , Martín-Ventura José Luis , Huelmos Ana , Gutiérrez-Landaluce Carlos , López-Castillo Marta , Kallmeyer Andrea , Cánovas Ester , Alonso Joaquín , López Bescós Lorenzo , Egido Jesús , Lorenzo Óscar , Tuñón Jose
Published: April 2020

Introduction: Type-2 diabetes mellitus (T2DM) is associated with early and severe atherosclerosis. However, few biomarkers can predict cardiovascular events in this population. Methods: We followed 964 patients with coronary artery disease (CAD), assessing plasma levels of galectin-3, monocyte chemoattractant protein-1 (MCP-1), and N-terminal fragment of brain natriuretic peptide (NT-proBNP) at baseline. The secondary outcomes were acute ischemia and heart failure or death. The primary outcome was the combination of the secondary outcomes. Results. Two hundred thirty-two patients had T2DM. Patients with T2DM showed higher MCP-1 (144 (113–195) vs. 133 (105–173) pg/mL, p = 0.006) and galectin-3 (8.3 (6.5–10.5) vs. 7.8 (5.9–9.8) ng/mL, p = 0.049) levels as compared to patients without diabetes. Median follow-up was 5.39 years (2.81–6.92). Galectin-3 levels were associated with increased risk of the primary outcome in T2DM patients (Hazard ratio (HR) 1.57 (1.07–2.30); p = 0.022), along with a history of cerebrovascular events. Treatment with clopidogrel was associated with lower risk. In contrast, NT-proBNP and MCP-1, but not galectin-3, were related to increased risk of the event in nondiabetic patients (HR 1.21 (1.04–1.42); p = 0.017 and HR 1.23 (1.05–1.44); p = 0.012, respectively), along with male sex and age. Galectin-3 was also the only biomarker associated with the development of acute ischemic events and heart failure or death in T2DM patients, while, in nondiabetics, MCP-1 and NT-proBNP, respectively, were related to these events. Conclusion: In CAD patients, galectin-3 plasma levels are associated with cardiovascular events in patients with T2DM, and MCP-1 and NT-proBNP in those without T2DM.
Promises of Big Data and Artificial Intelligence in Nephrology and Transplantation
Authors: Thongprayoon Charat , Kaewput Wisit , Kovvuru Karthik , Hansrivijit Panupong , Kanduri Swetha R. , Bathini Tarun , Chewcharat Api , Leeaphorn Napat , Gonzalez-Suarez Maria L. , Cheungpasitporn Wisit
Published: April 2020

Kidney diseases form part of the major health burdens experienced all over the world. Kidney diseases are linked to high economic burden, deaths, and morbidity rates. The great importance of collecting a large quantity of health-related data among human cohorts, what scholars refer to as “big data”, has increasingly been identified, with the establishment of a large group of cohorts and the usage of electronic health records (EHRs) in nephrology and transplantation. These data are valuable, and can potentially be utilized by researchers to advance knowledge in the field. Furthermore, progress in big data is stimulating the flourishing of artificial intelligence (AI), which is an excellent tool for handling, and subsequently processing, a great amount of data and may be applied to highlight more information on the effectiveness of medicine in kidney-related complications for the purpose of more precise phenotype and outcome prediction. In this article, we discuss the advances and challenges in big data, the use of EHRs and AI, with great emphasis on the usage of nephrology and transplantation.
Comparative Study of Salivary, Duodenal, and Fecal Microbiota Composition Across Adult Celiac Disease
Authors: Panelli Simona , Capelli Enrica , Lupo Giuseppe Francesco Damiano , Schiepatti Annalisa , Betti Elena , Sauta Elisabetta , Marini Simone , Bellazzi Riccardo , Vanoli Alessandro , Pasi Annamaria , Cacciatore Rosalia , Bacchi Sara , Balestra Barbara , Pastoris Ornella , Frulloni Luca , Corazza Gino Roberto , Biagi Federico , Ciccocioppo Rachele
Published: April 2020

Background: Growing evidence suggests that an altered microbiota composition contributes to the pathogenesis and clinical features in celiac disease (CD). We performed a comparative analysis of the gut microbiota in adulthood CD to evaluate whether: (i) dysbiosis anticipates mucosal lesions, (ii) gluten-free diet restores eubiosis, (iii) refractory CD has a peculiar microbial signature, and (iv) salivary and fecal communities overlap the mucosal one. Methods: This is a cross-sectional study where a total of 52 CD patients, including 13 active CD, 29 treated CD, 4 refractory CD, and 6 potential CD, were enrolled in a tertiary center together with 31 controls. A 16S rRNA-based amplicon metagenomics approach was applied to determine the microbiota structure and composition of salivary, duodenal mucosa, and stool samples, followed by appropriate bioinformatic analyses. Results: A reduction of both α- and β-diversity in CD, already evident in the potential form and achieving nadir in refractory CD, was evident. Taxonomically, mucosa displayed a significant abundance of Proteobacteria and an expansion of Neisseria, especially in active patients, while treated celiacs showed an intermediate profile between active disease and controls. The saliva community mirrored the mucosal one better than stool. Conclusion: Expansion of pathobiontic species anticipates villous atrophy and achieves the maximal divergence from controls in refractory CD. Gluten-free diet results in incomplete recovery. The overlapping results between mucosal and salivary samples indicate the use of saliva as a diagnostic fluid.
The Impact of Tax Preferences on the Investment Attractiveness of Bonds for Retail Investors: The Case of Russia
Authors: Boldyreva Natalia B. , Reshetnikova Liudmila G. , Tarkhanova Elena A. , Pisarenko Zhanna V. , Kalayda Svetlana A.
Published: April 2020

The impact of tax incentives on the investment attractiveness of bonds for retail investors is assessed in the article. The paper presents a comparative empirical analysis of investment attractiveness of Russian bonds and bank deposits for domestic retail investors. We identify investment preferences of retail investors in Russia, analyze investment characteristics of deposits in Russian banks and a variety of bonds available for retail investors. Given the tax benefits of the recently introduced Individual Investment Account, we show that the real yield of investment in government bonds is over eight times higher than the yield of bank deposits. Despite higher risks of investing in bonds, we conclude that government bonds taking into account the tax benefits of the Individual Investment Account could be a realistic alternative to bank deposits for Russian retail investors.
Characterization of 4H- and 6H-Like Stacking Faults in Cross Section of 3C-SiC Epitaxial Layer by Room-Temperature μ-Photoluminescence and μ-Raman Analysis
Authors: Scuderi Viviana , Calabretta Cristiano , Anzalone Ruggero , Mauceri Marco , La Via Francesco
Published: April 2020

We report a comprehensive investigation on stacking faults (SFs) in the 3C-SiC cross-section epilayer. 3C-SiC growth was performed in a horizontal hot-wall chemical vapour deposition (CVD) reactor. After the growth (85 microns thick), the silicon substrate was completely melted inside the CVD chamber, obtaining free-standing 4 inch wafers. A structural characterization and distribution of SFs was performed by μ-Raman spectroscopy and room-temperature μ-photoluminescence. Two kinds of SFs, 4H-like and 6H-like, were identified near the removed silicon interface. Each kind of SFs shows a characteristic photoluminescence emission of the 4H-SiC and 6H-SiC located at 393 and 425 nm, respectively. 4H-like and 6H-like SFs show different distribution along film thickness. The reported results were discussed in relation with the experimental data and theoretical models present in the literature.
Erratum: Abdou, A. A. N. and Khamsi, M.A. Fixed Points of Kannan Maps in the Variable Exponent Sequence Spaces ℓp(·). Mathematics 2020, 8, 76
Authors: Abdou Afrah A. N. , Khamsi Mohamed Amine
Published: April 2020

Kannan maps have inspired a branch of metric fixed point theory devoted to the extension of the classical Banach contraction principle. The study of these maps in modular vector spaces was attempted timidly and was not successful. In this work, we look at this problem in the variable exponent sequence spaces lp(·). We prove the modular version of most of the known facts about these maps in metric and Banach spaces. In particular, our results for Kannan nonexpansive maps in the modular sense were never attempted before.
Comparative Transcriptomics Reveals Distinct Gene Expressions of a Model Ciliated Protozoan Feeding on Bacteria-Free Medium, Digestible, and Digestion-Resistant Bacteria
Authors: Zou Songbao , Zhang Qianqian , Gong Jun
Published: April 2020

Bacterivory is an important ecological function of protists in natural ecosystems. However, there are diverse bacterial species resistant to protistan digestion, which reduces the carbon flow to higher trophic levels. So far, a molecular biological view of metabolic processes in heterotrophic protists during predation of bacterial preys of different digestibility is still lacking. In this study, we investigated the growth performance a ciliated protozoan Tetrahymena thermophila cultivated in a bacteria-free Super Proteose Peptone (SPP) medium (control), and in the media mixed with either a digestion-resistant bacterial species (DRB) or a digestible strain of E. coli (ECO). We found the protist population grew fastest in the SPP and slowest in the DRB treatment. Fluorescence in situ hybridization confirmed that there were indeed non-digested, viable bacteria in the ciliate cells fed with DRB, but none in other treatments. Comparative analysis of RNA-seq data showed that, relative to the control, 637 and 511 genes in T. thermophila were significantly and differentially expressed in the DRB and ECO treatments, respectively. The protistan expression of lysosomal proteases (especially papain-like cysteine proteinases), GH18 chitinases, and an isocitrate lyase were upregulated in both bacterial treatments. The genes encoding protease, glycosidase and involving glycolysis, TCA and glyoxylate cycles of carbon metabolic processes were higher expressed in the DRB treatment when compared with the ECO. Nevertheless, the genes for glutathione metabolism were more upregulated in the control than those in both bacterial treatments, regardless of the digestibility of the bacteria. The results of this study indicate that not only bacterial food but also digestibility of bacterial taxa modulate multiple metabolic processes in heterotrophic protists, which contribute to a better understanding of protistan bacterivory and bacteria-protists interactions on a molecular basis.
Checking NEKs: Overcoming a Bottleneck in Human Diseases
Authors: Peres de Oliveira Andressa , Kazuo Issayama Luidy , Betim Pavan Isadora Carolina , Riback Silva Fernando , Diniz Melo-Hanchuk Talita , Moreira Simabuco Fernando , Kobarg Jörg
Published: April 2020

In previous years, several kinases, such as phosphoinositide 3-kinase (PI3K), mammalian target of rapamycin (mTOR), and extracellular-signal-regulated kinase (ERK), have been linked to important human diseases, although some kinase families remain neglected in terms of research, hiding their relevance to therapeutic approaches. Here, a review regarding the NEK family is presented, shedding light on important information related to NEKs and human diseases. NEKs are a large group of homologous kinases with related functions and structures that participate in several cellular processes such as the cell cycle, cell division, cilia formation, and the DNA damage response. The review of the literature points to the pivotal participation of NEKs in important human diseases, like different types of cancer, diabetes, ciliopathies and central nervous system related and inflammatory-related diseases. The different known regulatory molecular mechanisms specific to each NEK are also presented, relating to their involvement in different diseases. In addition, important information about NEKs remains to be elucidated and is highlighted in this review, showing the need for other studies and research regarding this kinase family. Therefore, the NEK family represents an important group of kinases with potential applications in the therapy of human diseases.
Sugar Content in Processed Foods in Spain and a Comparison of Mandatory Nutrition Labelling and Laboratory Values
Authors: Yusta-Boyo María José , Bermejo Laura M. , García-Solano Marta , López-Sobaler Ana M. , Ortega Rosa M. , García-Pérez Marta , Dal-Re Saavedra María Ángeles ,   on behalf of the SUCOPROFS Study Researchers
Published: April 2020

To reduce the sugar content of processed foods through reformulation, the first step is to determine the content of the largest sources of sugars in each country’s diet. The aim of this work was to describe the sugar content in the most commonly consumed processed foods in Spain and to compare that sugar’s labelling and laboratory analysis values (LVs and AVs, respectively) to confirm its adequacy. A sample of the 1173 most commonly consumed processed foods in Spain (28 groups; 77 subcategories) was collected. For each product, the total sugar content was compared according to its AV and LV. The median (25th –75th percentiles, interquartile range) sugar content by group was calculated for the total sample, and the groups were classified as “high sugar content” when this value was above 22.5 g/100g of product. The adequacy of the LV, according to the European Union (EU) tolerance requirements, was then evaluated, and each subcategory median was compared with the AV to determine its appropriateness via a median test for independent samples (p < 0.05). In total, 10 out of 28 groups presented high sugar content. Moreover, 98.4% of the products met the EU tolerance ranges. Finally, only one subcategory (“cured ham”) presented significant differences between the AV and LV median values (0.4 g vs. 0.1 g sugar/100g, p < 0.05). The groups of food products whose sugar content reduction could have the greatest impact on public health were identified. In addition, our study showed the high adequacy of LV with the EU labeling tolerance requirements, as well as the LV’s appropriateness as a tool to implement actions aimed at reducing sugar consumption.
L-Type Amino Acid Transporter 1-Utilizing Prodrugs of Ketoprofen Can Efficiently Reduce Brain Prostaglandin Levels
Authors: Montaser Ahmed , Lehtonen Marko , Gynther Mikko , Huttunen Kristiina M.
Published: April 2020

In order to efficiently combat neuroinflammation, it is essential to deliver the anti-inflammatory drugs to their target sites in the brain. Pro-drugs utilizing the L-type amino acid transporter 1 (LAT1) can be transported across the blood-brain barrier (BBB) and the cellular barriers of the brain’s parenchymal cells. In this study, we evaluated, for the first time, the efficacy of LAT1-utilizing prodrugs of ketoprofen (KPF) on cyclooxygenase (COX) enzymes in vitro and prostaglandin E2 production in vivo by using an enzymatic assay and liquid chromatography- tandem mass spectrometry method, respectively. Aliphatic amino acid-conjugated pro-drugs inhibited the peroxidase activity of COX in vitro in their intact form (85% inhibition, IC50 ≈ 1.1 µM and 79%, IC50 ≈ 2.3 µM), which was comparable to KPF (90%, IC50 ≈ 0.9). Thus, these compounds acted more as KPF derivatives rather than pro-drugs. In turn, aromatic amino acid-conjugated pro-drugs behaved differently. The ester pro-drug inhibited the COX peroxidase activity in vitro (90%, IC50 ≈ 0.6 µM) due to its bioconversion to KPF, whereas the amide pro-drug was inactive toward COX enzymes in vitro. However, the amide pro-drug released KPF in the mouse brain in sufficient and effective amounts measured as reduced PGE2 levels.
Imbalance of Drug Transporter-CYP450s Interplay by Diabetes and Its Clinical Significance
Authors: Yang Yiting , Liu Xiaodong
Published: April 2020

The pharmacokinetics of a drug is dependent upon the coordinate work of influx transporters, enzymes and efflux transporters (i.e., transporter-enzyme interplay). The transporter–enzyme interplay may occur in liver, kidney and intestine. The influx transporters involving drug transport are organic anion transporting polypeptides (OATPs), peptide transporters (PepTs), organic anion transporters (OATs), monocarboxylate transporters (MCTs) and organic cation transporters (OCTs). The efflux transporters are P-glycoprotein (P-gp), multidrug/toxin extrusions (MATEs), multidrug resistance-associated proteins (MRPs) and breast cancer resistance protein (BCRP). The enzymes related to drug metabolism are mainly cytochrome P450 enzymes (CYP450s) and UDP-glucuronosyltransferases (UGTs). Accumulating evidence has demonstrated that diabetes alters the expression and functions of CYP450s and transporters in a different manner, disordering the transporter–enzyme interplay, in turn affecting the pharmacokinetics of some drugs. We aimed to focus on (1) the imbalance of transporter-CYP450 interplay in the liver, intestine and kidney due to altered expressions of influx transporters (OATPs, OCTs, OATs, PepTs and MCT6), efflux transporters (P-gp, BCRP and MRP2) and CYP450s (CYP3As, CYP1A2, CYP2E1 and CYP2Cs) under diabetic status; (2) the net contributions of these alterations in the expression and functions of transporters and CYP450s to drug disposition, therapeutic efficacy and drug toxicity; (3) application of a physiologically-based pharmacokinetic model in transporter–enzyme interplay.
Recent Advances in Manufacturing Innovative Stents
Authors: Beshchasna Natalia , Saqib Muhammad , Kraskiewicz Honorata , Wasyluk Łukasz , Kuzmin Oleg , Duta Oana Cristina , Ficai Denisa , Ghizdavet Zeno , Marin Alexandru , Ficai Anton , Sun Zhilei , Pichugin Vladimir F. , Opitz Joerg , Andronescu Ecaterina
Published: April 2020

Cardiovascular diseases are the most distributed cause of death worldwide. Stenting of arteries as a percutaneous transluminal angioplasty procedure became a promising minimally invasive therapy based on re-opening narrowed arteries by stent insertion. In order to improve and optimize this method, many research groups are focusing on designing new or improving existent stents. Since the beginning of the stent development in 1986, starting with bare-metal stents (BMS), these devices have been continuously enhanced by applying new materials, developing stent coatings based on inorganic and organic compounds including drugs, nanoparticles or biological components such as genes and cells, as well as adapting stent designs with different fabrication technologies. Drug eluting stents (DES) have been developed to overcome the main shortcomings of BMS or coated stents. Coatings are mainly applied to control biocompatibility, degradation rate, protein adsorption, and allow adequate endothelialization in order to ensure better clinical outcome of BMS, reducing restenosis and thrombosis. As coating materials (i) organic polymers: polyurethanes, poly(ε-caprolactone), styrene-b-isobutylene-b-styrene, polyhydroxybutyrates, poly(lactide-co-glycolide), and phosphoryl choline; (ii) biological components: vascular endothelial growth factor (VEGF) and anti-CD34 antibody and (iii) inorganic coatings: noble metals, wide class of oxides, nitrides, silicide and carbide, hydroxyapatite, diamond-like carbon, and others are used. DES were developed to reduce the tissue hyperplasia and in-stent restenosis utilizing antiproliferative substances like paclitaxel, limus (siro-, zotaro-, evero-, bio-, amphi-, tacro-limus), ABT-578, tyrphostin AGL-2043, genes, etc. The innovative solutions aim at overcoming the main limitations of the stent technology, such as in-stent restenosis and stent thrombosis, while maintaining the prime requirements on biocompatibility, biodegradability, and mechanical behavior. This paper provides an overview of the existing stent types, their functionality, materials, and manufacturing conditions demonstrating the still huge potential for the development of promising stent solutions.
The Spread and Transmission of Sweet Potato Virus Disease (SPVD) and Its Effect on the Gene Expression Profile in Sweet Potato
Authors: Zhang Kai , Lu Huixiang , Wan Chuanfang , Tang Daobin , Zhao Yong , Luo Kai , Li Shixi , Wang Jichun
Published: April 2020

Sweet potato virus disease (SPVD) is the most devastating viral disease in sweet potato (Ipomoea batatas (L.) Lam.), causing substantial yield losses worldwide. We conducted a systemic investigation on the spread, transmission, and pathogenesis of SPVD. Field experiments conducted over two years on ten sweet potato varieties showed that SPVD symptoms first occurred in newly developed top leaves, and spread from adjacent to distant plants in the field. The SPVD incidence was mainly (but not only) determined by the resistance of the varieties planted, and each variety exhibited a characteristic subset of SPVD symptoms. SPVD was not robustly transmitted through friction inoculation, but friction of the main stem might contribute to a higher SPVD incidence rate compared to friction of the leaf and branch tissues. Furthermore, our results suggested that SPVD might be latent in the storage root. Therefore, using virus-free storage roots and cuttings, purposeful monitoring for SPVD according to variety-specific symptoms, and swiftly removing infected plants (especially during the later growth stages) would help control and prevent SPVD during sweet potato production. Comparative transcriptome analysis revealed that numerous genes involved in photosynthesis, starch and sucrose metabolism, flavonoid biosynthesis, and carotenoid biosynthesis were downregulated following SPVD, whereas those involved in monolignol biosynthesis, zeatin biosynthesis, trehalose metabolism, and linoleic acid metabolism were upregulated. Notably, critical genes involved in pathogenesis and plant defense were significantly induced or suppressed following SPVD. These data provide insights into the molecular changes of sweet potato in response to SPVD and elucidate potential SPVD pathogenesis and defense mechanisms in sweet potato. Our study provides important information that can be used to tailor sustainable SPVD control strategies and guide the molecular breeding of SPVD-resistant sweet potato varieties.
Genetic Network between Leaf Senescence and Plant Immunity: Crucial Regulatory Nodes and New Insights
Authors: Zhang Yi , Wang Hou-Ling , Li Zhonghai , Guo Hongwei
Published: April 2020

Leaf senescence is an essential physiological process that is accompanied by the remobilization of nutrients from senescent leaves to young leaves or other developing organs. Although leaf senescence is a genetically programmed process, it can be induced by a wide variety of biotic and abiotic factors. Accumulating studies demonstrate that senescence-associated transcription factors (Sen-TFs) play key regulatory roles in controlling the initiation and progression of leaf senescence process. Interestingly, recent functional studies also reveal that a number of Sen-TFs function as positive or negative regulators of plant immunity. Moreover, the plant hormone salicylic acid (SA) and reactive oxygen species (ROS) have been demonstrated to be key signaling molecules in regulating leaf senescence and plant immunity, suggesting that these two processes share similar or common regulatory networks. However, the interactions between leaf senescence and plant immunity did not attract sufficient attention to plant scientists. Here, we review the regulatory roles of SA and ROS in biotic and abiotic stresses, as well as the cross-talks between SA/ROS and other hormones in leaf senescence and plant immunity, summarize the transcriptional controls of Sen-TFs on SA and ROS signal pathways, and analyze the cross-regulation between senescence and immunity through a broad literature survey. In-depth understandings of the cross-regulatory mechanisms between leaf senescence and plant immunity will facilitate the cultivation of high-yield and disease-resistant crops through a molecular breeding strategy.
Flax (Linum usitatissimum L.): A Potential Candidate for Phytoremediation? Biological and Economical Points of View
Authors: Saleem Muhammad Hamzah , Ali Shafaqat , Hussain Saddam , Kamran Muhammad , Chattha Muhammad Sohaib , Ahmad Shoaib , Aqeel Muhammad , Rizwan Muhammad , Aljarba Nada H. , Alkahtani Saad , Abdel-Daim Mohamed M.
Published: April 2020

Flax (Linum usitatissimum L.) is an important oil seed crop that is mostly cultivated in temperate climates. In addition to many commercial applications, flax is also used as a fibrous species or for livestock feed (animal fodder). For the last 40 years, flax has been used as a phytoremediation tool for the remediation of different heavy metals, particularly for phytoextraction when cultivated on metal contaminated soils. Among different fibrous crops (hemp, jute, ramie, and kenaf), flax represents the most economically important species and the majority of studies on metal contaminated soil for the phytoextraction of heavy metals have been conducted using flax. Therefore, a comprehensive review is needed for a better understanding of the phytoremediation potential of flax when grown in metal contaminated soil. This review describes the existing studies related to the phytoremediation potential of flax in different mediums such as soil and water. After phytoremediation, flax has the potential to be used for additional purposes such as linseed oil, fiber, and important livestock feed. This review also describes the phytoremediation potential of flax when grown in metal contaminated soil. Furthermore, techniques and methods to increase plant growth and biomass are also discussed in this work. However, future research is needed for a better understanding of the physiology, biochemistry, anatomy, and molecular biology of flax for increasing its pollutant removal efficiency.