bluuebunny/crossref_metadata_2025_split huggingface dataset:
Retinoic Acid Induces Functionally Suppressive Foxp3+RORγt+ T Cells In Vitro
Authors: Martínez-Blanco Mónica , Lozano-Ojalvo Daniel , Pérez-Rodríguez Leticia , Benedé Sara , Molina Elena , López-Fandiño Rosina 
Published: August 2021

IntroductionCD4+ T cells with regulatory function co-expressing Foxp3 and RORγt are linked to the development of oral tolerance towards innocuous food antigens in mice. This study aimed to discern the role played by IL-6 and retinoic acid (RA) in the in vitro generation of Foxp3+RORγt+ T cells and to investigate whether such cells have suppressive properties.MethodsCD4+CD25- T cells isolated from the spleen of BALB/c mice, were stimulated in the presence of IL-2 alone or together with TFG-β and different concentrations of IL-6 and/or RA. Percentage of Foxp3+, RORγt+, IL-17+, Foxp3+RORγt-, Foxp3+RORγt+, and Foxp3-RORγt+ T cells within the total CD4+ T cell population, production of cytokines (IL-10 and IL-17A) and gene expression (Foxp3, Rorc, Tgfb1, Il6, Il10, and Il17) were assessed at different time points. The phenotype and ability of cells generated from CD4+CD44-CD62L+ cells in the presence of RA to suppress effector T cell proliferation was assessed.ResultsTGF-β plus IL-6 induced the generation of Foxp3+ and double positive Foxp3+RORγt+ T cells to a higher extent than TGF-β alone at the beginning of the incubation period, although expression of Foxp3 subsequently declined. RA, added to TGF-β, increased Foxp3 and Rorc expression and Foxp3 and RORγt transcription and promoted the differentiation of Foxp3+RORγt- and Foxp3+RORγt+ cells that expressed and secreted IL-17. Foxp3+ T cells generated in vitro in presence of RA were functionally suppressive.ConclusionsUnder the influence of IL-2 and TGF-β, suppressive Foxp3+RORγt+ T cells that express and secrete IL-17 can be produced in vitro and RA further contributes to stabilize this phenotype.
Surface and Size Effects on the Behaviors of Point Defects in Irradiated Crystalline Solids
Authors: Ozturk Abdurrahman , Gencturk Merve , Ahmed Karim 
Published: August 2021

We present an elaborate study of the surface and size effects on the transient and steady-state behaviors of point defects in irradiated solids. In this investigation, both pure Ni and binary Ni-Cr were utilized as model systems. We utilize the spatially-resolved rate-theory (SRRT) modeling approach, and directly account for the effects of dose rate, production bias, and defects recombination, reactions with volumetric sinks, and diffusion to surface sinks. Several simulations were conducted to investigate the effects of these parameters in both coupled and decoupled manners. In the presence of production bias, the effects of surface and size persist even as the surface to volume ratio decreases. This was associated with a surface-induced and size-regulated instability. This instability is only triggered above a critical size between 100 and 500 nm. The critical size decreases with increasing dose rate, increasing production bias, or lowering the temperature. Moreover, this instability results in a pattern that favors the separation of vacancies and interstitials. Once this pattern develops, anomalies in the dependence on size for the transient and steady-state concentrations of point defects and the surface/boundary sink strength are observed. These anomalies tend to render irradiation damage more severe. For pure Ni, it was shown that vacancy supersaturation increases with size, and the rate of increase also rises with size. For the binary Ni-Cr system, it was shown that the magnitude of enrichment/depletion of Ni/Cr at the boundary increases with size, and the width of the enrichment/depletion layer also increases with size. The results obtained here agree well with experimental observations in irradiated materials such as the formation of void denuded zones adjacent to grain boundaries and the size and temperature dependence of the radiation resistance of nanomaterials. The size-dependent behaviors reported here also shed new light on the radiation tolerance of nanomaterials, i.e., the irradiation-induced instabilities are suppressed in such materials. Lastly, the implications of the results obtained here on the development of efficient reduced order models or the utilization of ion irradiation as a surrogate to neutron irradiation are discussed.
Urinary Proteomics Identifying Novel Biomarkers for the Diagnosis and Phenotyping of Carotid Artery Stenosis
Authors: Wang Wei , Wu Jianqiang , Liu Peng , Tang Xiaoyue , Pang Haiyu , Xie Ting , Xu Fang , Shao Jiang , Chen Yuexin , Liu Bao , Zheng Yuehong 
Published: August 2021

Background: Carotid artery stenosis (CAS) is caused by the formation of atherosclerotic plaques inside the arterial wall and accounts for 20–30% of all strokes. The development of an early, noninvasive diagnostic method and the identification of high-risk patients for ischemic stroke is essential to the management of CAS in clinical practice.Methods: We used the data-independent acquisition (DIA) technique to conduct a urinary proteomic study in patients with CAS and healthy controls. We identified the potential diagnosis and risk stratification biomarkers of CAS. And Ingenuity pathway analysis was used for functional annotation of differentially expressed proteins (DEPs). Furthermore, receiver operating characteristic (ROC) analysis was performed to evaluate the diagnostic values of DEPs.Results: A total of 194 DEPs were identified between CAS patients and healthy controls by DIA quantification. The bioinformatics analysis showed that these DEPs were correlated with the pathogenesis of CAS. We further identified 32 DEPs in symptomatic CAS compared to asymptomatic CAS, and biological function analysis revealed that these proteins are mainly related to immune/inflammatory pathways. Finally, a biomarker panel of six proteins (ACP2, PLD3, HLA-C, GGH, CALML3, and IL2RB) exhibited potential diagnostic value in CAS and good discriminative power for differentiating symptomatic and asymptomatic CAS with high sensitivity and specificity.Conclusions: Our study identified novel potential urinary biomarkers for noninvasive early screening and risk stratification of CAS.
Visual Field Reconstruction in Hemianopia Using fMRI Based Mapping Techniques
Authors: Halbertsma Hinke N. , Bridge Holly , Carvalho Joana , Cornelissen Frans W. , Ajina Sara 
Published: August 2021

PurposeA stroke that includes the primary visual cortex unilaterally leads to a loss of visual field (VF) representation in the hemifield contralateral to the damage. While behavioral procedures for measuring the VF, such as perimetry, may indicate that a patient cannot see in a particular area, detailed psychophysical testing often detects the ability to perform detection or discrimination of visual stimuli (“blindsight”). The aim of this study was to determine whether functional magnetic resonance imaging (fMRI) could be used to determine whether perimetrically blind regions of the VF were still represented in VF maps reconstructed on the basis of visually evoked neural activity.MethodsThirteen patients with hemianopia and nine control participants were scanned using 3T MRI while presented with visual stimulation. Two runs of a dynamic “wedge and ring” mapping stimulus, totaling approximately 10 min, were performed while participants fixated centrally. Two different analysis approaches were taken: the conventional population receptive field (pRF) analysis and micro-probing (MP). The latter is a variant of the former that makes fewer assumptions when modeling the visually evoked neural activity. Both methods were used to reconstruct the VF by projecting modeled activity back onto the VF. Following a normalization step, these “coverage maps” can be compared to the VF sensitivity plots obtained using perimetry.ResultsWhile both fMRI-based approaches revealed regions of neural activity within the perimetrically “blind” sections of the VF, the MP approach uncovered more voxels in the lesioned hemisphere in which a modest degree of visual sensitivity was retained. Furthermore, MP-based analysis indicated that both early (V1/V2) and extrastriate visual areas contributed equally to the retained sensitivity in both patients and controls.ConclusionIn hemianopic patients, fMRI-based approaches for reconstructing the VF can pick up activity in perimetrically blind regions of the VF. Such regions of the VF may be particularly amenable for rehabilitation to regain visual function. Compared to conventional pRF modeling, MP reveals more voxels with retained visual sensitivity, suggesting it is a more sensitive approach for VF reconstruction.
Modern Technology in Multi-Shell Diffusion MRI Reveals Diffuse White Matter Changes in Young Adults With Relapsing-Remitting Multiple Sclerosis
Authors: Beaudoin Ann-Marie , Rheault François , Theaud Guillaume , Laberge Frédéric , Whittingstall Kevin , Lamontagne Albert , Descoteaux Maxime 
Published: August 2021

ObjectiveTo characterize microstructural white matter changes related to relapsing-remitting multiple sclerosis using advanced diffusion MRI modeling and tractography. The association between imaging data and patient’s cognitive performance, fatigue severity and depressive symptoms is also explored.MethodsIn this cross-sectional study, 24 relapsing-remitting multiple sclerosis patients and 11 healthy controls were compared using high angular resolution diffusion imaging (HARDI). The imaging method includes a multi-shell scheme, free water correction to obtain tissue-specific measurements, probabilistic tracking algorithm robust to crossing fibers and white matter lesions, automatic streamlines and bundle dissection and tract-profiling with tractometry. The neuropsychological evaluation included the Symbol Digit Modalities Test, Paced Auditory Serial Addition Test, Modified Fatigue Impact Scale and Beck Depression Inventory-II.ResultsBundle-wise analysis by tractometry revealed a difference between patients and controls for 11 of the 14 preselected white matter bundles. In patients, free water corrected fractional anisotropy was significantly reduced while radial and mean diffusivities were increased, consistent with diffuse demyelination. The fornix and left inferior fronto-occipital fasciculus exhibited a higher free water fraction. Eight bundles showed an increase in total apparent fiber density and four bundles had a higher number of fiber orientations, suggesting axonal swelling and increased organization complexity, respectively. In the association study, depressive symptoms were associated with diffusion abnormalities in the right superior longitudinal fasciculus.ConclusionTissue-specific diffusion measures showed abnormalities along multiple cerebral white matter bundles in patients with relapsing-remitting multiple sclerosis. The proposed methodology combines free-water imaging, advanced bundle dissection and tractometry, which is a novel approach to investigate cerebral pathology in multiple sclerosis. It opens a new window of use for HARDI-derived measures and free water corrected diffusion measures. Advanced diffusion MRI provides a better insight into cerebral white matter changes in relapsing-remitting multiple sclerosis, namely diffuse demyelination, edema and increased fiber density and complexity.
Chronic Sensing of Subthalamic Local Field Potentials: Comparison of First and Second Generation Implantable Bidirectional Systems Within a Single Subject
Authors: Cummins Daniel D. , Kochanski Ryan B. , Gilron Roee , Swann Nicole C. , Little Simon , Hammer Lauren H. , Starr Philip A. 
Published: August 2021

BackgroundMany adaptative deep brain stimulation (DBS) paradigms rely upon the ability to sense neural signatures of specific clinical signs or symptoms in order to modulate therapeutic stimulation. In first-generation bidirectional neurostimulators, the ability to sense neural signals during active stimulation was often limited by artifact. Newer devices, with improved design specifications for sensing, have recently been developed and are now clinically available.ObjectiveTo compare the sensing capabilities of the first-generation Medtronic PC + S and second-generation Percept PC neurostimulators within a single patient.MethodsA 42-year-old man with Parkinson’s disease was initially implanted with left STN DBS leads connected to a PC + S implantable pulse generator. Four years later, the PC + S was replaced with the Percept PC. Local field potential (LFP) signals were recorded, both with stimulation OFF and ON, at multiple timepoints with each device and compared. Offline processing of time series data included artifact removal using digital filtering and template subtraction, before subsequent spectral analysis. With Percept PC, embedded processing of spectral power within a narrow frequency band was also utilized.ResultsIn the absence of stimulation, both devices demonstrated a peak in the beta range (approximately 20 Hz), which was stable throughout the 4-year period. Similar to previous reports, recordings with the PC + S during active stimulation demonstrated significant stimulation artifact, limiting the ability to recover meaningful LFP signal. In contrast, the Percept PC, using the same electrodes and stimulation settings, produced time series data during stimulation with spectral analysis revealing a peak in the beta-band. Online analysis by the Percept demonstrated a reduction in beta-band activity with increasing stimulation amplitude.ConclusionThis report highlights recent advances in implantable neurostimulator technology for DBS, demonstrating improvements in sensing capabilities during active stimulation between first- and second-generation devices. The ability to reliably sense during stimulation is an important step toward both the clinical implementation of adaptive algorithms and the further investigation into the neurophysiology underlying movement disorders.
Chronic Cadmium Exposure Alters Cardiac Matrix Metalloproteinases in the Heart of Sprague-Dawley Rat
Authors: Das Sandra Concepcion , Varadharajan Kavitha , Shanmugakonar Muralitharan , Al-Naemi Hamda A. 
Published: August 2021

The aim of this study was to evaluate the role of chronic cadmium exposure in modulating cardiac matrix metalloproteinases (MMPs) in the heart of rats. Adult male Sprague-Dawley rats were exposed to 15 ppm CdCl2 in drinking water for 10 weeks followed by withdrawal of cadmium treatment for 4 weeks. Following the completion of the treatment, gene expression of inflammatory mediators (IL-1β, IL-6, IL-10, TNF-α and NF-κB), protein expression of MMP-2, MMP-9 and their respective inhibitors- TIMP-1 and TIMP-2, and gelatinolytic activity of MMP-2 and MMP-9 were determined. At the protein level, cadmium incites a differential effect on the expression and activity of gelatinases and their endogenous inhibitors in an exposure-dependent manner. Results also show that the administered cadmium dose elicits an inflammatory response until week 10 that slightly diminishes after 4 weeks. This study provides evidence of cadmium-induced imbalance in the MMP-TIMP system in the cardiac tissue. This imbalance may be mediated by cadmium-induced inflammation that could contribute to various cardiovascular pathologies.
Preclinical Pharmacokinetics, Tissue Distribution, and Primary Safety Evaluation of Indo5, a Novel Selective Inhibitor of c-Met and Trks
Authors: Luo Teng , Zhang Fei-Xiang , Zhao Ke , Gao Hui-Ying , Zhang Shou-Guo , Wang Lin , Dou Gui-Fang , Liu Ting , Yu Miao , Zhan Yi-Qun , Chen Hui , Yang Xiao-Ming , Li Chang-Yan 
Published: August 2021

The compound [3-(1H-benzimidazol-2-methylene)-5-(2-methylphenylaminosulfo)-2-indolone], known as Indo5, is a novel selective inhibitor of c-Met and Trks, and it is a promising anticancer candidate against hepatocellular carcinoma (HCC). Assessing the pharmacokinetic properties, tissue distribution, and toxicity of Indo5 is critical for its medicinal evaluation. A series of sensitive and specific liquid chromatography-tandem mass spectrometry methods were developed and validated to determine the concentration of Indo5 in rat plasma and tissue homogenates. These methods were then applied to investigate the pharmacokinetics and tissue distribution of Indo5 in rats. After intravenous injection of Indo5, the maximum concentration (Cmax) and the time at which Cmax was reached (Tmax) were 1,565.3 ± 286.2 ng/ml and 1 min, respectively. After oral administration, Cmax and Tmax were 54.7 ± 10.4 ng/ml and 2.0 ± 0.48 h, respectively. We calculated the absolute oral bioavailability of Indo5 in rats to be 1.59%. Following intravenous injection, the concentrations of Indo5 in various tissues showed the following order: liver &gt; kidney ≈ heart &gt; lung ≈ large intestine ≈ small intestine ≈ stomach &gt; spleen &gt; brain ≈ testes; hence, Indo5 distributed highest in the liver and could not cross the blood–brain or blood–testes barriers. Continuous injection of Indo5 for 21 days did not lead to liver injury, considering unchanged ALT and AST levels, normal histological architecture of the liver, and normal number and frequencies of immune cells in the liver, indicating a very low toxicity of Indo5 in vivo. Collectively, our findings provide a comprehensive understanding of the biological actions of Indo5 in vivo and further support its development as an antitumor treatment for HCC patients.
D-Serine: A Cross Species Review of Safety
Authors: Meftah Amir , Hasegawa Hiroshi , Kantrowitz Joshua T. 
Published: August 2021

Background:D-Serine, a direct, full agonist at theD-serine/glycine modulatory site of the N-methyl-D-aspartate-type glutamate receptors (NMDAR), has been assessed as a treatment for multiple psychiatric and neurological conditions. Based on studies in rats, concerns of nephrotoxicity have limitedD-serine research in humans, particularly using high doses. A review ofD-serine's safety is timely and pertinent, asD-serine remains under active study for schizophrenia, both directly (R61 MH116093) and indirectly throughD-amino acid oxidase (DAAO) inhibitors. The principal focus is on nephrotoxicity, but safety in other physiologic and pathophysiologic systems are also reviewed.Methods:Using the search terms “D-serine,” “D-serine and schizophrenia,” “D-serine and safety,” “D-serine and nephrotoxicity” in PubMed, we conducted a systematic review onD-serine safety.D-serine physiology, dose-response and efficacy in clinical studies anddAAO inhibitor safety is also discussed.Results:WhenD-serine doses &gt;500 mg/kg are used in rats, nephrotoxicity, manifesting as an acute tubular necrosis syndrome, seen within hours of administration is highly common, if not universal. In other species, however,D-serine induced nephrotoxicity has not been reported, even in other rodent species such as mice and rabbits. Even in rats,D--serine related toxicity is dose dependent and reversible; and does not appear to be present in rats at doses producing an acute Cmax of &lt;2,000 nmol/mL. For comparison, the Cmax ofD-serine 120 mg/kg, the highest dose tested in humans, is ~500 nmol/mL in acute dosing. Across all published human studies, only one subject has been reported to have abnormal renal values related toD-serine treatment. This abnormality did not clearly map on to the acute tubular necrosis syndrome seen in rats, and fully resolved within a few days of stopping treatment.DAAO inhibitors may be nephroprotective.D-Serine may have a physiologic role in metabolic, extra-pyramidal, cardiac and other systems, but no other clinically significant safety concerns are revealed in the literature.Conclusions:Even before considering human to rat differences in renal physiology, using current FDA guided monitoring paradigms,D-serine appears safe at currently studied maximal doses, with potential safety in combination withDAAO inhibitors.
Early Surveillance and Public Health Emergency Responses Between Novel Coronavirus Disease 2019 and Avian Influenza in China: A Case-Comparison Study
Authors: Zhang Tiantian , Wang Qian , Wang Ying , Bai Ge , Dai Ruiming , Luo Li 
Published: August 2021

Background: Since the novel coronavirus disease (COVID-19) has been a worldwide pandemic, the early surveillance and public health emergency disposal are considered crucial to curb this emerging infectious disease. However, studies of COVID-19 on this topic in China are relatively few.Methods: A case-comparison study was conducted using a set of six key time nodes to form a reference framework for evaluating early surveillance and public health emergency disposal between H7N9 avian influenza (2013) in Shanghai and COVID-19 in Wuhan, China.Findings: A report to the local Center for Disease Control and Prevention, China, for the first hospitalized patient was sent after 6 and 20 days for H7N9 avian influenza and COVID-19, respectively. In contrast, the pathogen was identified faster in the case of COVID-19 than in the case of H7N9 avian influenza (12 vs. 31 days). The government response to COVID-19 was 10 days later than that to avian influenza. The entire process of early surveillance and public health emergency disposal lasted 5 days longer in COVID-19 than in H7N9 avian influenza (46 vs. 41 days).Conclusions: The identification of the unknown pathogen improved in China between the outbreaks of avian influenza and COVID-19. The longer emergency disposal period in the case of COVID-19 could be attributed to the government's slower response to the epidemic. Improving public health emergency management could lessen the adverse social effects of emerging infectious diseases and public health crisis in the future.
Simultaneous Aerosol and Ocean Properties From the PolCube CubeSat Polarimeter
Authors: Stamnes Snorre , Baize Rosemary , Bontempi Paula , Cairns Brian , Chemyakin Eduard , Choi Young-Jun , Chowdhary Jacek , Hu Yongxiang , Jeong Minsup , Kang Kyung-In , Kim Sungsoo S. , Liu Xu , Loughman Robert , MacDonnell Dave , McCormick M. Patrick , Moon Bongkon , Omar Ali , Roithmayr Carlos M. , Sim Chae Kyung , Sun Wenbo , van Diedenhoven Bastiaan , Videen Gorden , Wasilewski Andrzej 
Published: August 2021

We quantify the performance of aerosol and ocean remote sensing products from the PolCube instrument using a previously developed polarimeter retrieval algorithm based on optimal estimation. PolCube is a modified version of the PolCam lunar instrument on the Korea Pathfinder Lunar Orbiter that has been optimized for Earth-Science observations of aerosol, ocean, and thin cloud optical properties. The objective of the PolCube instrument is to retrieve detailed fine-mode (pollution and smoke) and coarse-mode (sea-salt and dust) aerosol properties over the ocean for a range of light to heavy aerosol loadings using its polarimetric-imaging capability at multiple angles and wavelengths from 410−865 nm. An additional objective is to discriminate aerosols from thin clouds. PolCube’s retrieval performance of aerosol optical and microphysical properties and ocean products is quantitatively assessed. We estimate that PolCube can retrieve total aerosol optical depth at 555 nm (AOD555) within ±0.068, fine-mode AOD555 within ±0.078, and fine-mode single-scattering albedo within ±0.036, where all uncertainties are expressed as one standard deviation (1σ). PolCube’s accurate and high-resolution aerosol-retrieval products will provide unique spatial and temporal coverage of the Earth that can be used synergistically with other instruments, such as the Geostationary Environmental Monitoring Spectrometer to improve air-quality forecasting.