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关键词： Mathematical and Computational Engineering  

摘要： The extensive progression in the Internet of Vehicles (IoV) and the exponential upsurge in data consumption reflect the importance of big data in IoV. In general, big data has gained a significant attraction in academia and industry to provide valuable business intelligence and evidence-based decisions. This has been a key enabler for the advancement of the Internet of Vehicles (IoV) in which big data can be leveraged for efficient processing and valuable decisions. Moreover, data acquired from connected vehicles, traffic monitoring, social media feeds, and, crowd-sourcing can strengthen urban development and management. The purpose of this study is to synthesize a systematic review of all related research articles from January 2014 to September 2020 in well-alleged venues. We have rigorously surveyed the research papers to understand potential opportunities, methodologies, and challenges of using big data in IoV. This review shows that big data can play a key role in providing sound and valuable predictions and also provide a comprehensive analysis of several methods, tools, and techniques for the use of big data in IoV. Apart from reviewing the state-of-the-art studies of using big data in IoV, a taxonomy of the said also has been proposed. Furthermore, the article outlined and discussed several key challenges in IoV with notable recommendations and open research dimensions for using big data in IoV.

关键词： NMR   Biomacromolecule interaction   INPPL1   ITIM   Tyrosine phosphorylation   INOSITOL 5-PHOSPHATASE SHIP2   SH2 DOMAIN   PHOSPHATIDYLINOSITOL 3,4,5-TRISPHOSPHATE   EXPRESSION   PROTEIN   RHOA  

摘要： SH2 domain-containing inositol 5-phosphatase 2 (SHIP2) plays an essential role in regulating phosphatidylinositol level in human cell, and is recruited to many phosphotyrosine (pY)-dependent signal transduction pathways by the SH2 domain. In immunity signaling, immunoreceptor Fc gamma RIIB binds to SHIP2-SH2 via its Y292-phosphorylated immunoreceptor tyrosine-based inhibitory motif (ITIM) and transmits inhibitory signal, which regulates B cell and neuronal cell activity and is associated with immune diseases and Alzheimer's disease. To date, the interaction between SHIP2 and Fc gamma RIIB has not been analyzed from a structural point of view. Here, the binding of SHIP2-SH2 with Y292-phosphorylated Fc gamma RIIB-ITIM was analyzed using NMR spectroscopy. The results demonstrated that SHIP2-SH2 mainly utilizes two regions including a pY-binding pocket and a specificity pocket formed by beta D, beta E, and EF-loop, to bind with Fc gamma RIIB-ITIM in high affinity. In addition to the two regions, the BG-loop of SHIP2-SH2 functions as an auxiliary interface enhancing affinity. By comparing the binding of SHIP2-SH2 with ligands from Fc gamma RIIB and c-MET, a hepatocyte growth factor receptor associated with tumorigenesis, significant differences in interface and affinity were found, suggesting that SHIP2-SH2 applies diverse patterns for binding to different ligand proteins. Moreover, S49, S51, and R70 of SHIP2 were identified to mediate the binding of both Fc gamma RIIB and c-MET, while R28 and Q107 were found to only participate in the binding of c-MET and Fc gamma RIIB respectively. Taken together, this study reveals the diverse mechanisms of SHIP2-SH2 for recognizing different ligands, and provides important clues for selectively manipulating various signaling pathways and specific drug design.

关键词： Seizure   Red blood cell distribution width   Intensive care unit   In-hospital mortality   eICU-CRD database   OXIDATIVE STRESS   HEART-FAILURE   LYMPHOCYTE RATIO   ACUTE PHYSIOLOGY   EPILEPSY   INFLAMMATION   IMPROVES   DISEASE   COHORT   SCORE  

摘要： Purpose The aim of this study was to determine the predictive value of red blood cell distribution width (RDW) in patients with a primary diagnosis of seizures admitted to the intensive care unit (ICU) in terms of in-hospital mortality. Methods This was a retrospective study of the eICU Collaborative Research Database of adult patients (aged 18-88 years) with a primary diagnosis of seizures in 2014 and 2015. The prognostic value of RDW was investigated using a receiver operating characteristic (ROC) curve, multiple logistic regression model, and net reclassification index (NRI). Results We identified 1568 patients who met the inclusion criteria. High RDW was significantly correlated with in-hospital mortality after adjusting for potential confounders with an odds ratio (OR) of 3.513 (95% confidence interval [CI]:1.699-7.266). The area under the ROC curve of RDW for in-hospital mortality was 0.7225. Compared with the prediction of in-hospital mortality using APACHE IV score alone, the continuous NRI with the RDW variable was 0.3507 (95%CI: 0.0584-0.6431, p < 0.05). The length of stay in the ICU of patients with an RDW >14.65% was significantly increased compared to those with normal RDW (log-rank test, p < 0.0001). Conclusion RDW width can be useful for prediction of in-hospital mortality in patients with seizures admitted to the ICU, and it provides additional prognostic value beyond the APACHE IV score alone.

关键词： ENVI-met   Model evaluation   Sensitivity analysis   Thermal-radiative performance   Urban greening   Urban climate   MEAN RADIANT TEMPERATURE   URBAN HEAT-ISLAND   MICROCLIMATE MODEL   MITIGATION   COMFORT   ENERGY   TREES   SIMULATIONS   STRATEGIES   FREIBURG  

摘要： Microclimate knowledge has been intensively integrated into urban planning and design to improve the buildings' energy performance and outdoor thermal comfort. To assess the climatic mitigation strategies, numerical modeling is gaining higher relevance. ENVI-met, a microclimate model to simulate the complex surfacevegetation-atmosphere interactions in the built environment, is receiving increasing popularity. This study aims to systematically evaluate the thermal-radiative performance of the ENVI-met model based on its recent updates. First, a field measurement was conducted in a subtropical city. Thermal-radiative parameters were collected besides three green infrastructure (GI) typologies (i.e., green roof, green wall, ground tree) and three corresponding reference sites. Second, sensitivity tests were conducted for the inputs and settings of ENVI-met model, including new radiation module IVS (Indexed View Sphere), meteorological boundary conditions, materials settings, and output intervals. Third, the thermal-radiative performance of ENVI-met was compared among the six measurement sites, three output intervals, and nine microclimate variables, based on four evaluation metrics. The results showed that 1) recent updates of ENVI-met can improve the estimation accuracy, especially with IVS on, radiation forcing, and localized materials settings; 2) ENVI-met was capable of simulating the thermal-radiative performance of three GI typologies simultaneously; 3) mobile measurement can be used for ENVI-met validation, and 4) model evaluation results were sensitive to the metrics. Overall, this study emphasized proper validation for ENVI-met before applications, when full forcing and localized settings are essential. The strengths and limitations of ENVI-met were discussed and implications were provided for model developers and users.

关键词： Giant cell arteritis   Major relapse   Prognosis   Stroke   PLACEBO-CONTROLLED TRIAL   LARGE-VESSEL INVOLVEMENT   DOUBLE-BLIND   POLYMYALGIA-RHEUMATICA   TEMPORAL ARTERITIS   INFLAMMATORY RESPONSE   METHOTREXATE   RISK   MULTICENTER   MAINTENANCE  

摘要： Objective: The relapse rate of giant cell arteritis (GCA) is around 48%. Major relapse of GCA is defined by the European League Against Rheumatism as severe ischemic or aortic (stenosis, aneurysm, or aortic dissection) disease of GCA. The objective of the present study was to determine the prevalence and incidence, as well as the spectrum of major relapse in GCA using published data. Methods: The MEDLINE and Cochrane databases were searched up to March 2020. Studies that included patients with newly diagnosed or relapsed GCA receiving glucocorticoids (GC) alone and/or GC-sparing therapy, detailing the number of relapsing patients and the characteristics of relapses were included. The prevalence and incidence of major relapse were pooled using a random-effects model. Results: Twenty-six studies (including eight randomised controlled trials) involving 2754 patients with GCA were included. The prevalence and incidence of major relapse in this population was 3.3% (95%CI [1.7;5.6]; I-2 = 86%) and 14.5/100 patient-years (95%CI [5.2;27.2]; I-2 = 90%). The clinical manifestations were jaw claudication (44.3%), ophthalmological involvement (32.7%), peripheral limb ischemia (12.5%), aortic (7.7%), and neurological involvements (4.8%). In the meta-regression analysis, the duration of follow-up was negatively associated with the incidence of major relapse (Beta = 0.015, 95%CI [ 0.026; 0.0042]; p = 0.0063). The incidence of major relapse was significantly higher in prospective studies (55.2/100 person-years, 95%CI [15.3;114.3] than in retrospective studies (4.1/100 patient-years, 95%CI[1.1;8.4]; pinteraction = 0.000.2). Conclusion: This study found that there was heterogeneity among studies, and this is partially related to study design. Jaw claudication was frequent and increases the prevalence and incidence of relapses major.

关键词： Cytoreductive Surgery   Ipilimumab   Nephrectomy   Nivolumab   Renal cell carcinoma   SOLID TUMORS   SUNITINIB  

摘要： Objectives: With the emergence of several effective combination therapies, information on their effects at the primary site will be crucial for planning future cytoreductive nephrectomy (CN). The present study focused exclusively on changes in primary tumor sizes following treatment with nivolumab plus ipilimumab and investigated the clinical factors associated with a good response in primary tumors. Methods and materials: We retrospectively assessed 27 patients diagnosed with advanced renal cell carcinoma (RCC) who started treatment with nivolumab plus ipilimumab. Changes in tumor sizes at the primary site were described using waterfall and spider plots, respectively. We analyzed the correlation of tumor shrinkage between primary and metastatic site. The parameters analyzed between responders and non-responders according to primary tumor sizes were International Metastatic Renal Cell Carcinoma Database Consortium (IMDC) risk scores, peripheral blood markers, and CRP. Results: The median age and follow-up period were 66 years and 9.3 months, respectively. The median IMDC risk score was 3 (range: 1-6). Nineteen patients were diagnosed with clear-cell RCC (ccRCC) and 8 patients with non-ccRCC. Among ccRCC patients, 9 (47.4%) achieved a significant response with a maximum reduction of 30% or more in the size of the primary tumor from baseline within 4 months, while 3 (37.5%) out of 8 patients with non-ccRCC achieved a significant response. Shrinkage of the primary tumor correlated with the metastatic tumors in both ccRCC and non-ccRCC cases. Of note, 6 patients underwent CN and no viable tumor cells were detected in the surgical specimens of 3 patients whose primary tumors shrank by approximately 50%-60% with a reduction to 4 cm or less. Among ccRCC patients, the neutrophil-to-lymphocyte ratio and monocyte-to-lymphocyte ratio were slightly lower in responders than in non-responders (P = 0.0944 and P = 0.0691). The platelet-to-lymphocyte ratio was significantly lower in

关键词： Sanfilippo   MPS-III   Heparan sulfate   Metabolic labeling   Cell line   HEPARAN-SULFATE PROTEOGLYCAN   EXPRESSION   CULTURE  

摘要： To evaluate a new approach to Mucopolysaccharidosis type IIIA (MPS-IIIA), work was initiated on primary fibroblasts from a well-known mouse model in which sulfamidase deficiency correlates with the accumulation of heparan sulfate - the hallmark of this disease. Once the culture of fibroblasts was established, we observed continuous proliferation with a rapid growth rate, loss of contact inhibition and late passage stability, corresponding to a spontaneously immortalized cell line. The presence of the single point D31N mutation was verified and both rapid and abundant intracellular accumulation of low molecular weight HS was observed, confirming both genotype and phenotype. This cell line is a potential in vitro model system for future studies of MPS-IIIA prior to employing animal models.

关键词： Human induced pluripotent stem cells   Multi-electrode arrays   Patch-clamp electrophysiology   Human neurons   Glutamate   GABA   Benchmarking   NETWORK ACTIVITY   MICROELECTRODE ARRAYS   SEIZURE LIABILITY   SYNAPTIC ACTIVITY   CORTICAL-NEURONS   GLUTAMATE   BURST   NMDA   EXPRESSION   CULTURES  

摘要： Human induced pluripotent stem cell (iPSC)-derived neurons are of interest for studying neurological disease mechanisms, developing potential therapies and deepening our understanding of the human nervous system. However, compared to an extensive history of practice with primary rodent neuron cultures, human iPSC-neurons still require more robust characterization of expression of neuronal receptors and ion channels and functional and predictive pharmacological responses. In this study, we differentiated human amniotic fluid-derived iPSCs into a mixed population of neurons (AF-iNs). Functional assessments were performed by evaluating electrophysiological (patch-clamp) properties and the effect of a panel of neuropharmacological agents on spontaneous activity (multi-electrode arrays; MEAs). These electrophysiological data were benchmarked relative to commercially sourced human iPSC-derived neurons (CNS.4U from Ncardia), primary human neurons (ScienCell (TM)) and primary rodent cortical/hippocampal neurons. Patch-clamp whole-cell recordings showed that mature AF-iNs generated repetitive firing of action potentials in response to depolarizations, similar to that of primary rodent cortical/hippocampal neurons, with nearly half of the neurons displaying spontaneous post-synaptic currents. Immunochemical and MEA-based analyses indicated that AF-iNs were composed of functional glutamatergic excitatory and inhibitory GABAergic neurons. Principal component analysis of MEA data indicated that human AF-iN and rat neurons exhibited distinct pharmacological and electrophysiological properties. Collectively, this study establishes a necessary prerequisite for AF-iNs as a human neuron culture model suitable for pharmacological studies. Graphic Abstract

关键词： Cell cycle   Adjuvant chemotherapy   Immunotherapy   Pancreatic ductal adenocarcinoma   R/BIOCONDUCTOR PACKAGE   CANCER   SUBTYPES   TUMORS   GEMCITABINE  

摘要： A major clinical challenge for treating patients with pancreatic ductal adenocarcinoma (PDAC) is identifying those that may benefit from adjuvant chemotherapy versus those that will not. Thus, there is a need for a robust and convenient biomarker for predicting chemotherapy response in PDAC patients. In this study, network inference was conducted by integrating the differentially expressed cell cycle signatures and target genes between the basal-like subtype and classical subtype of PDAC. As a result from this statistical analysis, two dominant cell cycle genes, RASAL2 and ASPM, were identified. Based on the expression levels of these two genes, we constructed a "Enhanced Cell Cycle" scoring system (ECC score). Patients were given an ECC score, and respectively divided into ECC-high and ECC-low groups. Survival, pathway enrichment, immune environment characteristics, and chemotherapy response analysis' were performed between the two groups in a total of 891 patients across 5 cohorts. ECC-high patients exhibited shortened recurrence-free survival (RFS) and overall survival (OS) rates. In addition, it was found that adjuvant chemotherapy could significantly improve the outcome of the ECC-high patients while ECC-low patients did not benefit from adjuvant chemotherapy. It was also found that there was less CD8+ T cell, natural killer (NK) cell, M1 macrophage, and plasma cell infiltration in ECC-high patients when compared to ECC-low patients. Also, the expression of CD73, an immune suppressor gene, and it's related hypoxia pathway were elevated in the ECC-high group when compared to the ECC-low group. In conclusion, this study showed that patients characterized as ECC-high not only had reduced RFS and OS rates, but were also more sensitive to adjuvant chemotherapy and could potentially be less sensitive to immune checkpoint inhibitors. Being able to characterize patients by these parameters would allow doctors to make more informed decisions on patient treatment regimen

关键词： Continuous glucose monitoring   HbA1c   Insulin therapy   Type 2 diabetes   TECHNOLOGY  

摘要： Aim: This prospective, observational cohort study aimed to measure HbA1c change over 3-6 months in type 2 diabetes managed with basal-bolus insulin and FreeStyle Libre (R) Flash Glucose Monitoring System (FSL) use compared to self-monitored blood glucose (SMBG). Methods: Sixteen Italian hospitals enrolled patients with type 2 diabetes (n = 322, [109 FSL, 213 SMBG users]) using basal-bolus insulin therapy for >= 1 year, HbA1c 8.0-12.0% (64-108 mmol/mol), new to FSL use (<3 months) or continuing with SMBG (controls). Eligible FSL and SMBG users were matched (1:2 ratio) for baseline HbA1c (within +/- 0.5%, recorded <= 3 months previously), study site and baseline data collection date. Results: Overall, baseline HbA1c was 8.9 +/- 0.8% (74 +/- 9 mmol/mol), age 67.2 +/- 10.0 years, BMI 30.5 +/- 6.5 kg/m(2) and insulin use duration 8.6 +/- 6.6 years (mean +/- SD), 56.2% were males. After 3-6 months, 234 complete cases (83 FSL, 151 SMBG users) demonstrated significantly reduced HbA1c for FSL use compared to SMBG (0.3% +/- 0.12 [3 mmol/mol +/- 1.3, (mean +/- SE)], p = 0.0112). The difference remained statistically significant after adjusting for confounders. Conclusions: HbA1c significantly improved in basal-bolus treated type 2 diabetes after flash glucose monitoring use for 3-6 months compared to SMBG. (C) 2021 The Authors. Published by Elsevier B.V.