gebhart/patrepeval huggingface dataset:
Dopaminergic Properties and Experimental Anti-Parkinsonian Effects of IPX750 in Rodent Models of Parkinson Disease (2004)

With a view toward improving the neural bioavailability of administered dopaminergic compounds, including dopamine, synthetic efforts have been directed toward enhancing the brain bioavailability of these compounds by accessing cellular sugar transport systems with stereoselective dopaminergic drugs. While synthesis and chemistry of the resultant class of compounds has recently been described in US Patent No. 6,548,484, the associated biologic properties have not previously been reported. One member of this new class, IPX-750, is a pro-drug dopamine-gluconamine designed to retain stereospecificity of binding at: glucose transporters (GLUT 1/GLUT 3 and intestinal Na/glucose co-transporters SGLT1), dopamine transporter (DAT); and, dopaminergic receptors of the D1/D2 families. Designed to be cleavable by tissue amidases, results reported here show that intact IPX-750 pro-drug retains dopaminergic agonist binding and biologic activities both in vitro and in vivo. IPX-750, like dopamine, exhibited predominant D5/D1 binding specificity with lower binding activity at D2. As expected, binding was highly stereo-specific, ie, IPX-760, a benzamide differing in just a hydrogen atom and keto oxygen from IPX-750, bound with 6-fold lower activity at D5. In cell culture, activation resulted from binding of IPX-750 at D1 or D5 in transfected cells was measured by increased intracellular cAMP. Interestingly, considering prior reported in vitro toxicity of dopamine oxidized and metabolic product dopamine, no evidence of in vitro toxicity was observed at up to 72 hrs in cell cultures at the EC50 of IPX-750 for increasing intracellular cAMP. IPX-750 was evaluated in the Parkinson's disease animal models, including MPTP mouse model, the 6-hydroxydopamine (6-OHDA) rat model and the Nurr1(+/-) knockout mouse model. In MPTP-lesioned and Nurr1+/- knockout mice, IPX-750 significantly increased Rota-rod time. In 6-OHDA-lesioned rats, IPX-750 significantly decreased apomorphine (APO)-induced rotation. Worthy of note, after cessation of IPX-750 treatments the anti-parkinsonian activity in MPTP-lesioned and Nurr1+/- mice required about 2 weeks to washout, suggesting a possible biologic reservoir of drug. In addition, after eight weeks of twice daily administration of 20 mg/kg IPX-750, mice did not show statistical difference in the total number of TH-positive neurons in substantia nigra (SN). These combined results suggest (i) that stereo-specific glycoconjugation may be an effective method to improve penetrability of drugs through the blood brain barrier; (ii) treatment with bioavailable IPX-750 in vitro did not show evidence for neurotoxicity; and, (iii) IPX-750 possesses dopaminergic properties and exerts anti-parkinsonian effects in three different PD rodent models, suggesting therapeutic potential for this new class of drugs in treating dopamine deficiency diseases.
Controlled study of oxatomide vs disodium chromoglycate for treating adverse reactions to food. (1992)

A controlled, cross-over trial was carried out to compare the efficacy and safety of oxatomide vs disodium chromoglycate (DSCG) for treating food allergy and intolerance. Twenty patients (15F, 5M; mean age 36.6 years), with chronic urticaria (twelve patients) or eczema (eight patients) caused by food allergy (ten cases) or food intolerance (ten cases), were treated with oxatomide (60 mg/day in a single evening administration) and with DSCG (2000 mg/day) for six weeks. The two treatments were separated by a 3-week wash-out period. All the patients completed the trial. During the treatment, both drugs succeeded in controlling the symptoms. With oxatomide, the wheals totally disappeared from 75% of the patients (p = 0.00135), the eczematous lesions disappeared from 64% (p = 0.056), and the itching from 70% (p = 0.00012); the figures for DSCG were 33%, 50% (p = 0.038) and 50%, respectively. Both drugs were well tolerated and there was no need to discontinue the treatment of any of the patients.
Visual Interfaces for Recommendation Systems (2018)

Recommendation applications can guide users in making important life choices by referring to the activities of similar peers. For example, students making academic plans may learn from the data of similar students, while patients and their physicians may explore data from similar patients to select the best treatment. Selecting an appropriate peer group has a strong impact on the value of the guidance that can result from analyzing the peer group data. In this article, we describe a visual interface that helps users review the similarity and differences between a seed record and a group of similar records and refine the selection. We introduce the LikeMeDonuts, Ranking Glyph, and History Heatmap visualizations. The interface was refined through three rounds of formative usability evaluation with 12 target users, and its usefulness was evaluated by a case study with a student review manager using real student data. We describe three analytic workflows observed during use and summarize how users’ input shaped the final design.
Insulin-like growth factor-II mRNA-binding protein 3 predicts a poor prognosis for colorectal adenocarcinoma (2013)

Insulin-like growth factor-II mRNA-binding protein 3 (IMP3) has been recently identified as a marker of aggressive behavior in several types of tumors. The aim of the present study was to detect the expression of the IMP3 protein in colorectal adenocarcinoma (CRA) and to identify a correlation with the clinicopathological features of the disease. IMP3 was evaluated in 186 samples of CRA using immunohistochemical methods. The correlation between IMP3 expression and the clinicopathological features of colorectal cancer was evaluated by the χ<sup>2</sup> and Fisher's exact tests. Survival rates were calculated using the Kaplan-Meier method and the correlation between IMP3 protein expression and the prognosis of patients with CRA was analyzed using Cox analysis. Of the 186 adjacent normal mucosa (ANM) cases, the 22 that exhibited dysplasia demonstrated weak IMP3 expression and the 164 without dysplasia showed no expression. Of the 186 CRA cases, immunohistochemical staining for IMP3 was observed in 143 cases (76.9%). A comparison of IMP3 expression between the CRA and ANM samples revealed stronger immunohistochemical reactivity in the CRA tissues (P<0.01). High IMP3 expression was associated with differentiation, lymphoid metastasis, TNM stage, Ki-67 labeling index and a poor patient outcome (P<0.05). In the multivariate analysis, IMP3 emerged as an independent predictor of survival. The present study demonstrated that IMP3 is able to promote the aggressiveness of cancer behavior, resulting in a poor prognosis for patients with CRA. Consequently, IMP3 may be regarded as a novel proliferation and prognostic indicator for patients with CRA.
Common and Rare Variants in SCN10A Modulate the Risk of Atrial Fibrillation (2014)

The common variant A1073 is associated with increased susceptibility to AF. Both rare and common variants have effect on the function of the channel, indicating that these variants influence susceptibility to AF. Hence, our study suggests that SCN10A variations are involved in the genesis of AF.
Edge Computing for the Internet of Things (2018)

By moving data computation and service supply from the cloud to the edge, edge computing has become a promising solution to address the limitations of cloud computing in supporting delay-sensitive and context-aware services in the Internet of Things (IoT) era. Instead of performing data storage and computing in a cluster of clouds, edge computing emphasizes leveraging the power of local computing and using different types of nearby devices/architectures as edge servers to provide timely and intelligent services. In this way, it can bring many advantages, including highly improved scalability by timely and intelligent service supply and local distributed computing that makes full use of client computing capabilities to meet the requirements of contextual computing. However, to truly realize edge computing in IoT applications, there are still many challenges that need to be addressed, such as how to efficiently distribute and manage data storage and computing, how to make edge computing collaborate with cloud computing for more scalable services, as well as how to secure and preserve the privacy of the whole system. The purpose of this Special Issue is to investigate the current research trends, and to help stakeholders in industry and academia to better understand challenges, recent advances, and potential research directions in the developing field of edge computing. Through an open call for papers and rigorous peer review, we selected 20 articles from 63 submissions as representatives of ongoing research and development activities. These 20 articles not only encompass a wide range of research topics in edge computing, but also bring some prominent research outcomes in transparent computing. We briefly divide the accepted articles into categories and discuss them briefly.
CRISPR-Cas: New Tools for Genetic Manipulations from Bacterial Immunity Systems (2015)

Prokaryotic CRISPR-Cas loci encode proteins that function as an adaptive immune system against infectious viruses and plasmids. Immunity is mediated by Cas nucleases and small RNA guides, which specify a cleavage site within the genome of the invader. In type II CRISPR-Cas systems, the RNA-guided Cas9 nuclease cleaves the DNA. Cas9 can be reprogrammed to create double-strand DNA breaks in the genomes of a variety of organisms, from bacteria to human cells. Repair of Cas9 lesions by homologous recombination or nonhomologous end joining mechanisms can lead to the introduction of specific nucleotide substitutions or indel mutations, respectively. Furthermore, a nuclease-null Cas9 has been developed to regulate endogenous gene expression and to label genomic loci in living cells. Targeted genome editing and gene regulation mediated by Cas9 are easy to program, scale, and multiplex, allowing researchers to decipher the causal link between genetic and phenotypic variation. In this review, we describe the most notable applications of Cas9 in basic biology, translational medicine, synthetic biology, biotechnology, and other fields.
Fractures of the facial skeleton (2015)

fractures of the facial skeleton , fractures of the facial skeleton , کتابخانه دیجیتالی دانشگاه علوم پزشکی ارومیه
Immunocytological detection of residual marrow disease at clinical remission predicts metastatic relapse in small cell lung cancer. (1990)

A panel of monoclonal antibodies against neural and epithelial associated antigens was used to examine bone marrow from patients in clinical remission from small cell lung cancer (SCLC). A standard peroxidase-antiperoxidase technique and Ficoll-Hypaque enrichment were used to detect SCLC-like cells at the 1-2% level of contamination in 8 of 12 patients who were disease free by conventional criteria, including routine marrow cytology and histology and endobronchoscopic biopsy or cytology. Six of these patients ultimately relapsed, with metastatic sites found between 2 and 6 months after restaging. Furthermore, 6 patients had undergone chemointensification including autologous marrow rescue with radical irradiation to the primary lung tumor. Four of these 6 subsequently relapsed, also with metastatic sites. Of the 4 patients without bone marrow metastases at restaging using this technique, 2 relapsed, with cells found at the primary site, and 2 remained in complete remission. Serum free cell culture was attempted in 9 of 12 cases and SCLC-like cell colonies grew, in suspension, in 4. The SCLC-like nature of these cells has been confirmed by electron microscopy in 1 case and by repeat immunocytochemistry for small cell associated antigens in 3 cases. Bone marrow positivity using these techniques appears to predict a high risk of metastatic relapse regardless of further therapy.
Endovascular Restorative Neurosurgery: A Novel Concept for Molecular and Cellular Therapy of the Nervous System (2003)

The amalgam of molecular biology and neurosurgery offers immense promise for neurorestoration and the management of neurodegenerative deficiencies, developmental disorders, neoplasms, stroke, and trauma. This article summarizes present strategies for and impediments to gene therapy and stem cell therapy of the central nervous system and advances the concept of a potential new approach, namely endovascular restorative neurosurgery. The objectives of gene transfer to the central nervous system are efficient transfection of host cells, selective sustained expression of the transgene, and lack of toxicity or immune excitation. The requisite elements of this process are the identification of candidate diseases, the construction of vehicles for gene transfer, regulated expression, and physical delivery. In the selection of target disorders, the underlying genetic events to be overcome, as well as their spatial and temporal distributions, must be considered. These factors determine the requirements for the physical dispersal of the transgene, the duration of transgene expression, and the quantity of transgene product needed to abrogate the disease phenotype. Vehicles for conveying the transgene to the central nervous system include viral vectors (retroviruses, lentiviruses, adenoviruses, adeno-associated viruses, and herpes simplex virus), liposomes, and genetically engineered cells, including neural stem cells. Delivery of the transgene into the brain presents several challenges, including limited and potentially risky access through the cranium, sensitivity to volumetric changes, restricted diffusion, and the blood-brain barrier. Genetic or cellular therapeutic agents may be injected directly into the brain parenchyma (via stereotaxy or craniotomy), into the cerebrospinal fluid (in the ventricles or cisterns), or into the bloodstream (intravenously or intra-arterially). The advantages of the endovascular route include the potential for widespread distribution, the ability to deliver large volumes, limited perturbation of neural tissue, and the feasibility of repeated administration.
Donepezil, a centrally acting acetylcholinesterase inhibitor,alleviates learning deficits in hypocholinergic models in rats (2000)

Donepezil is a member of a new class of centrally acting cholinesterase inhibitors which preferentially inhibit acetylcholinesterase rather than butyrylcholinesterase. The effects of donepezil on learning impairments were investigated in some hypocholinergic models in rats. In nucleus basalis magnocellularis (NBM)-lesioned rats, donepezil alleviated deficits in passive avoidance response at a dose of 0.125 mg/kg and higher, while tacrine had only a tendency toward improved performance. Donepezil at 0.5 mg/kg effectively counteracted acquisition impairments in the water maze task induced by lesions of the medial septum; tacrine had no significant effects on impairments in this task. Scopolamine caused an increase of errors in the 8-arm radial maze. Donepezil significantly decreased scopolamine-induced errors in the radial maze at 0.5 mg/kg, whereas tacrine decreased errors at 2 mg/kg. These results suggest that donepezil can clearly minimize learning impairments induced by treatments that cause central cholinergic deficiencies in rats. These findings support the clinical efficacy of donepezil in Alzheimer's disease.
Abstract 21281: Cardiosphere-Derived Cell and Mesenchymal Stem Cell Extracellular Vesicles Contain Distinct RNA Cargo (2017)

Introduction: Cardiosphere-derived cells (CDCs) possess regenerative, immunomodulatory and cardioprotective characteristics when delivered to the heart post-myocardial infarction (MI). CDCs derived from different donors possess variable regenerative potency in a MI model. We previously demonstrated that human CDC-derived extracellular vesicles (CDC-EVs) recapitulate the effects of CDCs in acute and chronic in vivo MI models. We are testing the hypothesis that a distinct cargo profile defines the functional efficacy between CDC-EVs and mesenchymal stem cell-derived EVs (MSC-EVs). Also, we assessed the immunomodulatory role of CDC-EVs derived from potent and non-potent CDCs in comparison with MSC-EVs. Methods: CDCs or MSCs were cultured in serum-free medium for 15 days and the conditioned media was concentrated by ultrafiltration to isolate EVs. The miRNeasy Serum/Plasma kit was used to extract total RNA from EVs followed by small RNA sequencing (NextSeq 500, Illumina) (CDC-EVs, n =12; MSC-EVs, n =4). We performed an in vitro and in vivo macrophage assay to assess the immunomodulatory role of EVs. Results: RNA sequencing analysis of CDC-EVs and MSC-EVs revealed a greater overall abundance of Y-RNA fragments and miRNA in CDC-EVs. Examining the specific Y-RNA classes, we found that MSC-EVs contained an expression profile with lower Y4 (p&lt;0.05) but higher Y5 (p&lt;0.05) Y-RNA fragments. Four miRNAs (miR-146a, miR-151, miR-409, miR-423) were highly enriched in CDC-EVs while miR-10a and miR-4792 were more abundant in MSC-EVs. EVs from potent CDCs showed a stronger upregulation of anti-inflammatory genes in activated macrophages ( in vitro ) and prevented accumulation of macrophages ( in vivo ) when compared with EVs obtained from non-potent CDCs or MSCs. Conclusions: We demonstrated that CDC-EVs contain a unique RNA cargo set that can differentiate CDC-EVs from MSC-EVs. The higher presence of Y-RNA in CDC-EVs as compared to MSC-EVs could be responsible for the ability of CDCs to regulate stem cell activation and tissue regeneration. The highly enriched panel of miRNAs observed in CDC-EVs and the ability to reduce the inflammatory reaction by macrophages, in contrast to MSC-EVs, suggest that they may support some of the functional benefits observed post-MI.
Hierarchical Vertex Regression-Based Segmentation of Head and Neck CT Images for Radiotherapy Planning (2017)

Segmenting organs at risk from head and neck CT images is a prerequisite for the treatment of head and neck cancer using intensity modulated radiotherapy. However, accurate and automatic segmentation of organs at risk is a challenging task due to the low contrast of soft tissue and image artifact in CT images. Shape priors have been proved effective in addressing this challenging task. However, conventional methods incorporating shape priors often suffer from sensitivity to shape initialization and also shape variations across individuals. In this paper, we propose a novel approach to incorporate shape priors into a hierarchical learning-based model. The contributions of our proposed approach are as follows: 1) a novel mechanism for critical vertices identification is proposed to identify vertices with distinctive appearances and strong consistency across different subjects; 2) a new strategy of hierarchical vertex regression is also used to gradually locate more vertices with the guidance of previously located vertices; and 3) an innovative framework of joint shape and appearance learning is further developed to capture salient shape and appearance features simultaneously. Using these innovative strategies, our proposed approach can essentially overcome drawbacks of the conventional shape-based segmentation methods. Experimental results show that our approach can achieve much better results than state-of-the-art methods.
Predicting progression of Alzheimer's disease (2010)

A simple, calculated progression rate at the initial visit gives reliable information regarding performance over time on cognition, global performance and activities of daily living. The slowest progression group also survives longer. This baseline measure should be considered in the design of long duration Alzheimer's disease clinical trials.
Interfacial Phenomena and Colloid Stability: Basic Principles (2015)

Interfacial Phenomena and Colloid Stability deals with the fundamental aspects of interfacial phenomena, which form the basis of applications of interface and colloid science to various disperse systems. These include suspensions, emulsions, nano-dispersions, wetting, spreading, deposition and adhesion of particles to surfaces. This book is valuable for research scientists and PhDs. investigating various aspects of interface and colloid science
Enhancing the in vivo expansion of adoptively transferred EBV-specific CTL with lymphodepleting CD45 monoclonal antibodies in NPC patients (2008)

Treatment of Epstein-Barr virus (EBV)-positive nasopharyngeal carcinoma (NPC) with EBV-specific cytotoxic T cells (EBV-specific CTL) has been promising, producing clinical responses. However, infused EBV-specific CTL did not expand in vivo, likely limiting their antitumor activity. Lymphodepleting patients with chemotherapy before T-cell transfer enhances in vivo T-cell expansion, but results in nonspecific destruction of the resident immune system and can have significant toxicity. To evaluate if monoclonal antibodies (mAbs) can produce a more selective lymphodepletion, we conducted a clinical study in which NPC patients received a pair of lymphodepleting mAbs targeted to the CD45 antigen (CD45 mAbs) before EBV-specific CTL infusion. Eight patients with recurrent NPC received CD45 mAbs followed by escalating doses of autologous EBV-specific CTL. Infusion of CD45 mAbs resulted in transient lymphopenia in all patients and an increase in interleukin-15 (IL-15) levels in 6 out 8 patients. All patients had an increase in their peripheral blood frequency of EBV-specific T cells after CTL infusion. Three patients with a persistent increase had clinical benefits including 1 complete response (> 24 months) and 2 with stable disease (for 12 and 15 months). Lymphodepleting mAbs prior CTL transfer may represent an alternative to chemotherapy to enhance expansion of infused CTL. This study is registered at (http://www.clinialtrials.gov) as NCT00608257.
Vascular endothelial growth factor inhibition is not an effective therapeutic strategy for relapsed or refractory multiple myeloma: a phase 2 study of pazopanib (GW786034) (2009)

To the editor:

Vascular endothelial growth factor (VEGF) stimulates plasma cell proliferation and migration in vitro, and preclinical studies have demonstrated that these effects can be blocked by inhibition of VEGF receptors (VEGFRs) in multiple myeloma (MM) cell lines.[1][1] Pazopanib (GW786034