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Open AccessArticle
Inhibition of JAK-STAT Signaling with Baricitinib Reduces Inflammation and Improves Cellular Homeostasis in Progeria Cells
Cells 2019, 8(10), 1276; https://doi.org/10.3390/cells8101276 (registering DOI) - 18 Oct 2019
Abstract
Hutchinson-Gilford progeria syndrome (HGPS), a rare premature aging disorder that leads to death at an average age of 14.7 years due to myocardial infarction or stroke, is caused by mutations in the LMNA gene. Nearly 90% of HGPS cases carry the G608G mutation [...] Read more.
Hutchinson-Gilford progeria syndrome (HGPS), a rare premature aging disorder that leads to death at an average age of 14.7 years due to myocardial infarction or stroke, is caused by mutations in the LMNA gene. Nearly 90% of HGPS cases carry the G608G mutation within exon 11 that generates a truncated prelamin A protein “progerin”. Progerin accumulates in HGPS cells and induces premature senescence at the cellular and organismal levels. Children suffering from HGPS develop numerous clinical features that overlap with normal aging, including atherosclerosis, arthritis, hair loss and lipodystrophy. To determine whether an aberrant signaling pathway might underlie the development of these four diseases (atherosclerosis, arthritis, hair loss and lipodystrophy), we performed a text mining analysis of scientific literature and databases. We found a total of 17 genes associated with all four pathologies, 14 of which were linked to the JAK1/2-STAT1/3 signaling pathway. We report that the inhibition of the JAK-STAT pathway with baricitinib, a Food and Drug Administration-approved JAK1/2 inhibitor, restored cellular homeostasis, delayed senescence and decreased proinflammatory markers in HGPS cells. Our ex vivo data using human cell models indicate that the overactivation of JAK-STAT signaling mediates premature senescence and that the inhibition of this pathway could show promise for the treatment of HGPS and age-related pathologies. Full article
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Open AccessFeature PaperArticle
Bending and Torsion Fatigue-Testing Machine Developed for Multiaxial Non-Proportional Loading
Metals 2019, 9(10), 1115; https://doi.org/10.3390/met9101115 (registering DOI) - 18 Oct 2019
Abstract
A new fatigue-testing machine was developed to perform high-cycle multiaxial fatigue tests at 50 Hz, in order to reduce testing time. The developed machine can combine bending and torsion loading and perform fatigue tests at a high frequency, under proportional and non-proportional loading [...] Read more.
A new fatigue-testing machine was developed to perform high-cycle multiaxial fatigue tests at 50 Hz, in order to reduce testing time. The developed machine can combine bending and torsion loading and perform fatigue tests at a high frequency, under proportional and non-proportional loading conditions, where the principal stress direction changes during a cycle. The proportional loading is cyclic bending loading, and the non-proportional loading is cyclic, combining bending and reversed torsion loading. In this study, the effectiveness of the testing machine was verified by conducting tests under these loading conditions, using specimens of type 490A hot-rolled steel and type 304 stainless steel. The fatigue life linked to bending loading obtained using the new testing machine was slightly extended compared with that obtained using the conventional fatigue-testing machine. The fatigue life derived as a result of a combination of bending and torsion was comparable to that obtained using the conventional fatigue-testing machine, although a fatigue limit reduction of 100 MPa was observed compared to the former study. The feasibility of tests using the developed multiaxial fatigue-testing machine was confirmed. Full article
(This article belongs to the Special Issue Multiaxial Fatigue: Testing and Modelling)
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Open AccessArticle
Radiotherapy for the Palliation of Advanced Sarcomas—The Effectiveness of Radiotherapy in Providing Symptomatic Improvement for Advanced Sarcomas in a Single Centre Cohort
Healthcare 2019, 7(4), 120; https://doi.org/10.3390/healthcare7040120 (registering DOI) - 18 Oct 2019
Abstract
Background: Sarcomas are rare and heterogeneous tumours with a large proportion of patients requiring palliative intervention. They are regarded as relatively radioresistant and therefore achieving good palliation with radiation may require larger doses than for more common solid tumour types. Limited data [...] Read more.
Background: Sarcomas are rare and heterogeneous tumours with a large proportion of patients requiring palliative intervention. They are regarded as relatively radioresistant and therefore achieving good palliation with radiation may require larger doses than for more common solid tumour types. Limited data is available regarding appropriate palliative radiotherapy dose fractionation. This case series aims to assess the effectiveness of radiotherapy in providing symptomatic improvement for advanced sarcomas. Method: Data was retrospectively collected for patients treated with palliative radiotherapy between July 2010 and April 2019 at one institution. The primary outcome was documented symptomatic improvement following radiotherapy. Secondary outcome was overall survival. Results: One hundred and five patients had a total of 137 sites treated using 25 different dose fractionation schedules. The median patient age was 54 (range 8–90) years. Treated sites included 114 soft tissue and 23 bone sarcomas. Data on symptomatic improvement was available in 56% and 67% of cases respectively. A total of 70% of soft tissue and 55% of bone sarcoma patients reported symptomatic improvement. Symptomatic response rates appeared to increase to a biological effective dose (BED) of 50Grey4 (Gy4) (alpha beta ratio (α/β) = 4 for tumour) but did not continue to improve with further rises in dose beyond this. Conclusion: Palliative radiotherapy offers symptomatic improvement for sarcoma patients with two-thirds of patients reporting reduction in symptoms. These results are limited by the heterogeneous study population including different sarcoma subtypes each with a probable different radio-sensitivity, treated with different radiotherapy schedules. Further prospective data collection is needed considering sarcoma subtype radio-sensitivity, to determine appropriate palliative dose fractionation schedules. Full article
(This article belongs to the Special Issue Radiotherapy and Cancer)
Open AccessArticle
Low Cross-Polarization Improved-Gain Rectangular Patch Antenna
Electronics 2019, 8(10), 1189; https://doi.org/10.3390/electronics8101189 (registering DOI) - 18 Oct 2019
Abstract
In this paper, a low cross-polarization improved-gain rectangular patch antenna is presented. A patch-ground shorting pin with defected patch structure (DPS) is introduced to suppress the cross-polarization level. A High Reflective Frequency Selective Surface (HRFSS) superstrate is designed and placed over the proposed [...] Read more.
In this paper, a low cross-polarization improved-gain rectangular patch antenna is presented. A patch-ground shorting pin with defected patch structure (DPS) is introduced to suppress the cross-polarization level. A High Reflective Frequency Selective Surface (HRFSS) superstrate is designed and placed over the proposed antenna at an optimized position to intensify the gain. To characterize the unit-cell of the superstrate, its transmission characteristics are extracted and discussed. Integration of the superstrate achieves a beam contraction resulting in a gain enhancement to 10.65 dBi. The proposed antenna has perfect broadside radiation with a cross-polarization level of below −30 dB in the entire half power beamwidth. The prototype of the antenna exhibits good agreement between experimental and simulated results. Full article
(This article belongs to the Section Microwave and Wireless Communications)
Open AccessCommunication
Equine Rhinitis A Virus Infection in Thoroughbred Racehorses—A Putative Role in Poor Performance?
Viruses 2019, 11(10), 963; https://doi.org/10.3390/v11100963 (registering DOI) - 18 Oct 2019
Abstract
The aim of this study was to identify respiratory viruses circulating amongst elite racehorses in a training yard by serological testing of serial samples and to determine their impact on health status and ability to race. A six-month longitudinal study was conducted in [...] Read more.
The aim of this study was to identify respiratory viruses circulating amongst elite racehorses in a training yard by serological testing of serial samples and to determine their impact on health status and ability to race. A six-month longitudinal study was conducted in 30 Thoroughbred racehorses (21 two-year-olds, five three-year-olds and four four-year-olds) during the Flat racing season. Sera were tested for the presence of antibodies against equine herpesvirus 1 and 4 (EHV-1 and EHV-4) and equine rhinitis viruses A and B (ERAV and ERBV) by complement fixation (CF) and equine arteritis virus (EAV) by ELISA. Antibodies against equine influenza (EI) were measured by haemagglutination inhibition (HI). Only ERAV was circulating in the yard throughout the six-month study period. Seroconversion to ERAV frequently correlated with clinical respiratory disease and was significantly associated with subsequent failure to race (p = 0.0009). Over 55% of the two-year-olds in the study seroconverted to ERAV in May and June. In contrast, only one seroconversion to ERAV was observed in the older horses. They remained free of any signs of respiratory disease and raced successfully throughout the study period. The importance of ERAV as a contributory factor in the interruption of training programmes for young horses may be underestimated. Full article
(This article belongs to the Special Issue Equine Viruses)
Open AccessArticle
Seismic Imaging of the Mesozoic Bedrock Relief and Geological Structure under Quaternary Sediment Cover: The Bolmin Syncline (SW Holy Cross Mountains, Poland)
Geosciences 2019, 9(10), 447; https://doi.org/10.3390/geosciences9100447 (registering DOI) - 18 Oct 2019
Abstract
The clear and detailed images of geological structures that can be obtained by seismic methods are one of the main drivers of their popularity in geological research. The quality of final geophysical images and models relies strongly on the amount of data that [...] Read more.
The clear and detailed images of geological structures that can be obtained by seismic methods are one of the main drivers of their popularity in geological research. The quality of final geophysical images and models relies strongly on the amount of data that goes into them. Analysing several complementary seismic datasets allow an improved interpretation. Responding to this challenge, this article proposed an optimal combination of geophysical methods for near-surface applications. Multi-channel analysis of surface waves, first-arrival travel-time tomography, and ground-penetrating radar were the key supports for standard reflection seismic imaging. Ease of use and fast and cheap acquisition are some of the advantages of the mentioned methods. Considering that all recorded wave fields required minimal additional processing while offering a significant improvement in the final stack, it was worth the extra effort. Thanks to that, the better-estimated velocity filed allowed high quality images to be obtained up to 200 m. The Mesozoic bedrock was a distinct and very strong reflector in the resulting reflection seismic imaging. There was also a clearly visible depression of the horizon corresponding to erosion or a structure (syncline). Deeper, it was possible to track two or even four detachments of faulting origin. Full article
(This article belongs to the Section Geophysics)
Open AccessArticle
Cerium Oxide Nanoparticles Absorption through Intact and Damaged Human Skin
Molecules 2019, 24(20), 3759; https://doi.org/10.3390/molecules24203759 (registering DOI) - 18 Oct 2019
Abstract
Cerium oxide (CeO2) nanoparticles (NPs) are used in polishing products and absorbents, as promoters in wound healing, and as organopesticide decontaminants. While systemic bioaccumulation and organ toxicity has been described after inhalation, data on CeO2 NPs’ transdermal permeation are lacking. [...] Read more.
Cerium oxide (CeO2) nanoparticles (NPs) are used in polishing products and absorbents, as promoters in wound healing, and as organopesticide decontaminants. While systemic bioaccumulation and organ toxicity has been described after inhalation, data on CeO2 NPs’ transdermal permeation are lacking. Our study was an in vitro investigation of the permeation of 17-nm CeO2 NPs dispersed in synthetic sweat (1 g L−1) using excised human skin on Franz cells. Experiments were performed using intact and needle-abraded skin, separately. The average amount of Ce into intact and damaged skin samples was 3.64 ± 0.15 and 7.07 ± 0.78 µg cm−2, respectively (mean ± SD, p = 0.04). Ce concentration in the receiving solution was 2.0 ± 0.4 and 3.3 ± 0.7 ng cm−2 after 24 h (p = 0.008). The Ce content was higher in dermal layers of damaged skin compared to intact skin (2.93 ± 0.71 µg cm−2 and 0.39 ± 0.16 µg cm−2, respectively; p = 0.004). Our data showed a very low dermal absorption and transdermal permeation of cerium, providing a first indication of Ce skin uptake due to contact with CeO2. Full article
(This article belongs to the Special Issue Biomedical Applications of Cerium-Doped Materials and Nanoceria)
Open AccessArticle
The Oncogenic Signaling Pathways in BRAF-Mutant Melanoma Cells are Modulated by Naphthalene Diimide-Like G-Quadruplex Ligands
Cells 2019, 8(10), 1274; https://doi.org/10.3390/cells8101274 (registering DOI) - 18 Oct 2019
Abstract
Melanoma is the most aggressive and deadly type of skin cancer. Despite the advent of targeted therapies directed against specific oncogene mutations, melanoma remains a tumor that is very difficult to treat, and ultimately remains incurable. In the past two decades, stabilization of [...] Read more.
Melanoma is the most aggressive and deadly type of skin cancer. Despite the advent of targeted therapies directed against specific oncogene mutations, melanoma remains a tumor that is very difficult to treat, and ultimately remains incurable. In the past two decades, stabilization of the non-canonical nucleic acid G-quadruplex structures within oncogene promoters has stood out as a promising approach to interfere with oncogenic signaling pathways in cancer cells, paving the way toward the development of G-quadruplex ligands as antitumor drugs. Here, we present the synthesis and screening of a library of differently functionalized core-extended naphthalene diimides for their activity against the BRAFV600E-mutant melanoma cell line. The most promising compound was able to stabilize G-quadruplexes that formed in the promoter regions of two target genes relevant to melanoma, KIT and BCL-2. This activity led to the suppression of protein expression and thus to interference with oncogenic signaling pathways involved in BRAF-mutant melanoma cell survival, apoptosis, and resistance to drugs. This G-quadruplex ligand thus represents a suitable candidate for the development of melanoma treatment options based on a new mechanism of action and could reveal particular significance in the context of resistance to targeted therapies of BRAF-mutant melanoma cells. Full article
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Open AccessArticle
A Novel Dermaseptin Isolated from the Skin Secretion of Phyllomedusa tarsius and Its Cationicity-Enhanced Analogue Exhibiting Effective Antimicrobial and Anti-Proliferative Activities
Biomolecules 2019, 9(10), 628; https://doi.org/10.3390/biom9100628 (registering DOI) - 18 Oct 2019
Abstract
A novel dermaseptin peptide, dermaseptin-PT9 (DPT9), was isolated and identified from Phyllomedusa tarsius by the combination of molecular cloning and LC-MS analysis. Chemically synthesised DPT9 was broadly effective against the tested microorganisms through the disruption of cell membranes and showed weak haemolytic activity [...] Read more.
A novel dermaseptin peptide, dermaseptin-PT9 (DPT9), was isolated and identified from Phyllomedusa tarsius by the combination of molecular cloning and LC-MS analysis. Chemically synthesised DPT9 was broadly effective against the tested microorganisms through the disruption of cell membranes and showed weak haemolytic activity towards horse erythrocytes. It also exhibited anti-proliferative effect against various human cancer cells. Moreover, an analogue with enhanced cationicity, K8, 23-DPT9, in which Asp8 and Glu23 were substituted by lysine residues, had a markedly increased antimicrobial effect against all tested microorganisms and disrupted microbial cell membranes. This analogue also showed no haemolysis at its effective antimicrobial concentrations. In addition, K8, 23-DPT9 displayed an enhanced anti-proliferative effect against cancer cells, while displayed weak activity against the normal human cell line, HMEC-1. Full article
Open AccessArticle
Considering Patients’ Empowerment in Chronic Care Management: A Cross-Level Approach
Eur. J. Investig. Health Psychol. Educ. 2020, 10(1), 134-142; https://doi.org/10.3390/ejihpe10010012 (registering DOI) - 18 Oct 2019
Abstract
This paper consists of an analysis of the concept of empowerment—which is often defined as a key issue in health care—at the macro, meso, and micro levels by focusing on health care reform in Belgium. Three research teams collected data and combined them [...] Read more.
This paper consists of an analysis of the concept of empowerment—which is often defined as a key issue in health care—at the macro, meso, and micro levels by focusing on health care reform in Belgium. Three research teams collected data and combined them in an inductive secondary analysis. Our preliminary results demonstrate that patient empowerment does not always encompass the same scientific reality. At the macro level, this concept is linked to the authorities’ wish to support at-home care for chronic patients. At the meso level, the role of caregivers in maintaining patients’ autonomy, but also the social conditions of their lives, is a salient component of empowerment. At the micro level, individual and personal features such as identity can influence patient empowerment and behavior in the health care system. This cross-level research suggests that patient empowerment is not sufficiently clearly defined at each level of the care production chain, which could impede the reform of health care. This paper underlines the polysemy of a concept viewed as a milestone in European health care policy and the necessity of a clear, collective definition to operationalize and implement it. Full article
Open AccessArticle
A Series of Field-Induced Single-Ion Magnets Based on the Seven-Coordinate Co(II) Complexes with the Pentadentate (N3O2) H2dapsc Ligand
Magnetochemistry 2019, 5(4), 58; https://doi.org/10.3390/magnetochemistry5040058 (registering DOI) - 18 Oct 2019
Abstract
A series of five new mononuclear pentagonal bipyramidal Co(II) complexes with the equatorial 2,6-diacetylpyridine bis(semicarbazone) ligand (H2dapsc) and various axial pseudohalide ligands (SCN, SeCN, N(CN)2, C(CN)3, and N3) was prepared and structurally characterizated: [Co(H2 [...] Read more.
A series of five new mononuclear pentagonal bipyramidal Co(II) complexes with the equatorial 2,6-diacetylpyridine bis(semicarbazone) ligand (H2dapsc) and various axial pseudohalide ligands (SCN, SeCN, N(CN)2, C(CN)3, and N3) was prepared and structurally characterizated: [Co(H2dapsc)(SCN)2]∙0.5C2H5OH (1), [Co(H2dapsc)(SeCN)2]∙0.5C2H5OH (2), [Co(H2dapsc)(N(CN)2)2]∙2H2O (3), [Co(H2dapsc)(C(CN)3)(H2O)](NO3)∙1.16H2O (4), and {[Co(H2dapsc)(H2O)(N3)][Co(H2dapsc)(N3)2]}N3∙4H2O (5). The combined analyses of the experimental and AC magnetic data of the complexes (1–5) and two other earlier described those of this family [Co(H2dapsc)(H2O)2)](NO3)2∙2H2O (6) and [Co(H2dapsc)(Cl)(H2O)]Cl∙2H2O (7), their theoretical description and the ab initio CASSCF/NEVPT2 calculations reveal large easy-plane magnetic anisotropies for all complexes (D = + 35 − 40 cm1). All complexes under consideration demonstrate slow magnetic relaxation with dominant Raman and direct spin–phonon processes at static magnetic field and so they belong to the class of field-induced single-ion magnets (SIMs). Full article
(This article belongs to the Special Issue Feature Papers in Magnetochemistry)
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Open AccessArticle
Satisfaction Level of Tuberculosis Patients Regarding Their Access to TB Care and Prevention Services, Delivered Through a Public–Private Mix Model in Pakistan
Healthcare 2019, 7(4), 119; https://doi.org/10.3390/healthcare7040119 (registering DOI) - 18 Oct 2019
Abstract
Objective: The private healthcare providers (PHCP) are believed to improve access to healthcare services in public–private mix (PPM) projects, as they are considered first point of contact for healthcare. The purpose of this study was to determine the satisfaction level of tuberculosis (TB) [...] Read more.
Objective: The private healthcare providers (PHCP) are believed to improve access to healthcare services in public–private mix (PPM) projects, as they are considered first point of contact for healthcare. The purpose of this study was to determine the satisfaction level of tuberculosis (TB) patients. Design: A questionnaire-based, cross-sectional study was carried out during November and December 2017 for 572 under-treatment patients registered with PHCPs in the PPM project. Lot quality assurance sampling technique was used to randomly select 19 districts from a sample frame of 75 districts. In each selected district, the data collector retrieved a TB register of 8 months (January–August 2017) and systematically selected patients by fixed periodic interval. SPSS version 24.0 (IBM Corp, Amonk, NY, USA) was used to analyze the data. Results: This study included 53% (n = 301) males and 47% (n = 271) females, with mean age of 38 years (SD, ±18). Almost half of the participants were illiterate (51%, n = 289), and 64% (n = 365) were non-earning members of the family. In practice, most of the participants visit private providers (71%, n = 407), including private hospitals/clinics (44%) and traditional practitioners (27%; n = 153); 55% of participants visited their current doctor because of the clinic’s proximity to their residence. Of the participants, 82% (n = 469) were satisfied with TB care services and 85% (n = 488) said that they would recommend this clinic to others. Conclusion: PHCPs are preferred providers for individuals, which is consistent with findings of other studies. Though they are satisfied with TB care and services, interventions should be introduced to reduce the financial burden on the patient. Partnering PHCP is a way forward to ensure universal health coverage and better health outcomes of the population. Full article
Open AccessArticle
Lithuanian Speech Recognition Using Purely Phonetic Deep Learning
Computers 2019, 8(4), 76; https://doi.org/10.3390/computers8040076 (registering DOI) - 18 Oct 2019
Abstract
Automatic speech recognition (ASR) has been one of the biggest and hardest challenges in the field. A large majority of research in this area focuses on widely spoken languages such as English. The problems of automatic Lithuanian speech recognition have attracted little attention [...] Read more.
Automatic speech recognition (ASR) has been one of the biggest and hardest challenges in the field. A large majority of research in this area focuses on widely spoken languages such as English. The problems of automatic Lithuanian speech recognition have attracted little attention so far. Due to complicated language structure and scarcity of data, models proposed for other languages such as English cannot be directly adopted for Lithuanian. In this paper we propose an ASR system for the Lithuanian language, which is based on deep learning methods and can identify spoken words purely from their phoneme sequences. Two encoder-decoder models are used to solve the ASR task: a traditional encoder-decoder model and a model with attention mechanism. The performance of these models is evaluated in isolated speech recognition task (with an accuracy of 0.993) and long phrase recognition task (with an accuracy of 0.992). Full article
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Open AccessArticle
Deformation Modeling of Flexible Pavement in Expansive Subgrade in Texas
Geosciences 2019, 9(10), 446; https://doi.org/10.3390/geosciences9100446 (registering DOI) - 18 Oct 2019
Abstract
The tendency of expansive subgrade soil to undergo swelling and shrinkage with the change in moisture has a significant impact on the performance of the pavement. The repeated cycles of wet and dry periods throughout a year lead to considerable stress concentration in [...] Read more.
The tendency of expansive subgrade soil to undergo swelling and shrinkage with the change in moisture has a significant impact on the performance of the pavement. The repeated cycles of wet and dry periods throughout a year lead to considerable stress concentration in the pavement subgrade soil. Such stress concentrations leads to the formation of severe pavement cracks. The objective of the research is to develop a prediction model to estimate the deformation of pavement over expansive subgrade. Two pavement sites—one farm to market road and one state highway—were monitored regularly using moisture and temperature sensors along with rain gauges. Additionally, geophysical testing was performed to obtain a continuous profile of the subgrade soil over time. Topographical surveying and horizontal inclinometer readings were taken to determine pavement deformation. The field monitoring data resulted in a maximum movement up to 80 mm in the farm to market road, and almost 38 mm in the state highway. The field data were statistically evaluated to develop a deformation prediction model. The validation of the model indicated that only a fraction of the deformation was reflected by seasonal variation, while inclusion of rainfall events in the equation significantly improved the model. Furthermore, the prediction model also incorporated the effects of change in temperature and resistivity values. The generated model could find its application in predicting pavement deformation with respect to rainfall at any time of the year. Full article
(This article belongs to the Special Issue Behavior of Expansive Soils and its Shrinkage Cracking)
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Open AccessArticle
Connectedness Between Natural Gas Price and BRICS Exchange Rates: Evidence from Time and Frequency Domains
Energies 2019, 12(20), 3970; https://doi.org/10.3390/en12203970 (registering DOI) - 18 Oct 2019
Abstract
In this paper, we investigate the connectedness between natural gas and BRICS (Brazil, Russia, India, China, and South Africa)’s exchange rate in terms of time and frequency. This empirical work is based on the approach of connectedness proposed by Diebold and Yilmaz, who [...] Read more.
In this paper, we investigate the connectedness between natural gas and BRICS (Brazil, Russia, India, China, and South Africa)’s exchange rate in terms of time and frequency. This empirical work is based on the approach of connectedness proposed by Diebold and Yilmaz, who provided an effective way of valuing how much variation in one variable is responsible for the value of other variables, and the method proposed by Baruník and Křehlík, who decomposed the results from Diebold and Yilmaz into different frequencies. We also use the rolling-window method to conduct time-varying analysis. The data used in this paper are from 23 August 2010 to 20 June 2019. We find that the natural gas price hardly influences BRICS’s exchange rates, which provides an important practical implication for policymakers, especially in oil-dependent countries. Full article
(This article belongs to the Special Issue Empirical Analysis of Natural Gas Markets)
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