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Impact of high dose vitamin C on platelet function

World Journal of Critical Care Medicine 2017年第1期6卷 37-47页

作者： Bassem M Mohammed Kimberly W Sanford Bernard J Fisher Erika J Martin daniel contaifer jr Urszula Osinska Warncke Dayanjan S Wijesinghe Charles E Chalfant Donald F Brophy Alpha A Fowler Ⅲ Ramesh Natarajan Department of Clinical Pharmacy Faculty of Pharmacy Cairo University Department of Pharmacotherapy and Outcomes Science Virginia Commonwealth University Department of Pathology Virginia Commonwealth University Division of Pulmonary Disease and Critical Care Medicine De-partment of Internal Medicine Virginia Commonwealth University Research and Development Hunter Holmes Mc Guire Veterans Administration Medical Center the Department of Biochemistry and Molecular Biology the VCU Massey Cancer Center the VCU Institute of Molecular Medicine and the VCU Johnson Center for Critical Care and Pulmonary Research Virginia Commonwealth University

AIM To examine the effect of high doses of vitamin C(VitC) on ex vivo human platelets(PLTs).METHODS Platelet concentrates collected for therapeutic or prophylactic transfusions were exposed to:(1) normal saline(control);(2) 0.3 mmol/L VitC(Lo VitC); or(3) 3 mmol/L VitC(Hi VitC, final concentrations) and stored appropriately. The Vit C additive was preservative-free buffered ascorbic acid in water, pH 5.5 to 7.0, adjusted with sodium bicarbonate and sodium hydroxide. The doses of Vit C used here correspond to plasma Vit C levels reported in recently completed clinical trials. Prior to supplementation, a baseline sample was collected for analysis. PLTs were sampled again on days 2, 5 and 8 and assayed for changes in PLT function by: Thromboelastography(TEG), for changes in viscoelastic properties; aggregometry, for PLT aggregation and adenosine triphosphate(ATP) secretion in response to collagen or adenosine diphosphate(ADP); and flow cytometry, for changes in expression of CD-31, CD41 a, CD62 p and CD63. In addition, PLT intracellular Vit C content was measured using a fluorimetric assay for ascorbic acid and PLT poor plasma was used for plasma coagulation tests [prothrombin time(PT), partial thrombplastin time(PTT), functional fibrinogen] and Lipidomics analysis(UPLC ESI-MS/MS).RESULTS VitC supplementation significantly increased PLTs intracellular ascorbic acid levels from 1.2 mmol/L at baseline to 3.2 mmol/L(Lo VitC) and 15.7 mmol/L(Hi VitC, P 0.05). PLT function assayed by TEG, aggregometry and flow cytometry was not significantly altered by Lo or Hi VitC for up to 5 d. However, PLTs exposed to 3 mmol/L VitC for 8 d demonstrated significantly increased R and K times by TEG and a decrease in the α-angle(P < 0.05). There was also a fall of 20 mm in maximum amplitude associated with the Hi VitC compared to both baseline and d

关键词： Platelet function Thromboelastography Flow cytometry Platelet lipidomics Vitamin C

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Sickle cell retinopathy and systemic disease

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Annals of Eye Science 2024年第2期9卷 53-61页

作者： Oladipupo O.Anibire daniel ABrill Basil K.Williams jr Meharry Medical College NashvilleTNUSA Department of Ophthalmology University of Cincinnati College of MedicineCincinnatiOHUSA Cincinnati Eye Institute CincinnatiOHUSA Bascom Palmer Eye Institute University of Miami Miller School of MedicineMiamiFLUSA

Sickle cell disease(SCD)is a widespread hemoglobinopathy that results in significant patient morbidity and *** occlusion can cause acute pain,acute chest syndrome,and avascular necrosis,while hemolysis and endothelial disruption can cause ischemic stroke,leg ulcers,pulmonary hypertension,and *** ocular and orbital structures can be affected by SCD ischemic events,including orbital bone infarction,ischemic optic neuropathy,retinal artery occlusion,hyphema,secondary glaucoma,sickle cell maculopathy,and sickle cell *** sickle cell retinopathy(PSR)is the most common cause of vision *** PSR can lead to macular ischemia,vitreous hemorrhage,and tractional retinal *** screening exams and multimodal imaging can lead to earlier detection of sickle cell retinopathy and improved patient *** patients undergoing vitreoretinal surgery may require coordination of care with hematologists to avoid ischemic *** hydroxyurea was the only United States Food and Drug Administration approved treatment for several decades,patients with SCD now have several more treatment *** the United States screening all infants for SCD,there can be delays in diagnosis and *** review article aims to provide an overview of sickle disease for the ophthalmologist,and to discuss emerging treatment options and current management of SCD ocular complications.

关键词： Sickle cell anemia sickle cell disease(SCD) sickle cell retinopathy retinal detachment vitreous hemorrhage(VH)

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Envita’s Precision Cancer Care: 35-Fold Improvement in Response Rates

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Journal of Cancer Therapy 2024年第4期15卷 99-120页

作者： Sheba Goklany John C. Oertle III Ronald Matthias jr. daniel Warren David Medina Rory Sears Robert Zieve Kendra Quart Christopher Aussems Jon Moma Shannon Miller Zach Poteet Conner Coffin Courtney Middleton Erika Ware Phylicia Zarnosky Julie Nowak Winlove Suasin daniel Conway Chad Burk Ruth Tan-Lim Dino Prato Envita Medical Centers Scottsdale AZ USA

New clinical approaches are imperative beyond the widely adopted National Comprehensive Cancer Network (NCCN) guidelines, utilized by prominent cancer institutions. Cancer is the leading cause of death among individuals younger than 85 years within the United States. Despite significant technological advances, including the expenditure of hundreds of billions, treatment outcomes and overall survival have not notably improved for most types of advanced cancer over the last several decades. Over the past 24 years, Envita Medical Centers has pioneered a unique form of personalized treatment approach for late-stage and refractory cancer patients, introducing groundbreaking innovations in the field. Our integrated algorithm utilizes advanced genomics, transcriptomics, and highly tailored immunotherapy, resulting in remarkable outcome improvements. This study presents Envita’s innovative personalized treatment algorithms and examines the response outcomes of 199 late-stage cancer patients treated at Envita Medical Centers over a two-year period. Compared to standard of care and palliative chemotherapy, Envita’s treatment demonstrated a remarkable 35-fold improvement in overall response rates (Figure 1). Moreover, 88% of the patients, the majority presenting with Stage 3 or 4 cancer, experienced a 43-fold improvement in quality of life with minimal side effects, as compared to standard of care chemotherapy and palliative care. This revolutionary success is attributed to Envita’s personalized therapeutic algorithms, which incorporate customized immunotherapy. Envita’s precision care approach has also achieved a 100% better response rate compared to over 65 global chemotherapy clinical trials with more than 2700 patients. The results from this study suggest that a wider utilization of Envita’s personalized approach can significantly benefit patients with late-stage and refractory cancer.

关键词： Envita Medical Centers Late-stage Cancer Overall Response Rate Quality of Life Circulating Tumor Cells (CTCs) Mutant Allele Frequency (MAF) Precision Care

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The Iberian Roma Population Variant Server(IRPVS)

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Journal of Genetics and Genomics 2024年第7期51卷 769-773页

作者： Fabiola Mavillard Javier Perez-Florido Francisco M.Ortuño Amador Valladares Miren L.Álvarez-Villegas Gema Roldán Rosario Carmona Manuel Soriano Santiago Susarte Pilar Fuentes daniel López-López Ana María Nuñez-Negrillo Alejandra Carvajal Yolanda Morgado daniel Arteaga Rosa Ufano Pablo Mir Juan F.Gamella Joaquín Dopazo Carmen Paradas Macarena Cabrera-Serrano Instituto de Biomedicina de Sevilla(IBiS) Hospital Universitario Virgen del Rocío/CSIC/Universidad de SevillaSevillaSpain Centro Investigación Biomédica en Red Enfermedades Neurodegenerativas(CIBERNED) Instituto de Salud CarlosⅢSevillaSpain Plataforma Andaluza de Medicina Computacional Fundación Progreso y Salud(FPS)Hospital Virgen del RocíoSevillaSpain Grupo de medicina computacional de sistemas Instituto de Biomedicina de Sevilla(IBiS)Hospital Virgen del RocíoSevillaSpain Nodo de Genómica Funcional (INB-ELIXIR-es)Fundación Progreso y Salud(FPS)Hospital Virgen del RocíoSevilla 41013Spain Bioinformática en Enfermedades raras(BiER) Centro de Investigación Biomédica en Red de Enfermedades Raras(CIBERER)Instituto de salud CarlosⅢSevillaSpain Departamento de Ingeniería de Computadores Automática y RobóticaUniversidad de GranadaGranadaSpain Servicio de Urgencias de Atención Primaria Distrito SevillaSevillaSpain Centro de Servicios Sociales Negociado de Servicios EspecializadosAyuntamiento de SevillaSevillaSpain Departamento de Enfermería Facultad de Ciencias de la SaludUniversidad de GranadaGranadaSpain Departamento de Neurología Hospital Virgen de las NievesGranadaSpain Departamento de Neurología Hospital Virgen de ValmeSevillaSpain Centro de Salud Utrera Sur SevillaSpain Centro de Salud Polígono Sur SevillaSpain Unidad de Trastornos del Movimiento Servicio de Neurología y Neurofisiología ClínicaHospital Universitario Virgen del RocíoSevillaSpain Departamento de Medicina Facultad de MedicinaUniversidad de SevillaSevilleSpain Departamento de Antropología Social Universidad de GranadaSpain Unidad Enfermedades Neuromusculares Servicio de Neurología y Neurofisiología ClínicaHospital Universitario Virgen del RocíoSevillaSpain

In recent years,the number of known disease genes has exponentially grown due to the widespread adoption of cost-effective massive parallel *** identify new disease variants,especially in monogenic disorders,a frequen... 详细信息

关键词： Server filtering massive

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Distribution Control Centers in the US and Europe:Commonalities,Differences,and Lessons

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Journal of Modern Power Systems and Clean Energy 2022年第2期10卷 259-268页

作者： Subramanian Vadari Izudin Dzafic Dan'l Koch Ryan Murphy daniel Hayes jr. Tarik Donlagic Modem Grid Solutions New YorkUSA University of Sarajevo Faculty of Electrical EngineeringSarajevoBosnia and Herzegovina R.Murphy are with Puget Sound Energy BellevueUSA Commonwealth Edison ChicagoUSA Siemens AG ErlanglenGermany

The distribution control center(DCC)has evolved from a sideshow in the traditional distribution service center to a major centerpiece of the utility moving into the decentralized ***,this is the place where much of the action is happening due to new forms of energy that are coining into the distribution *** creates the flexibility of operation and in-creased complexity due to the need for increased coordination between the transmission control center and ***,the US and European utilities have adapted to this change in very different ***,we describe the research works done in a DCC and their evolutions from the perspectives of major US utilities,and those enhanced by the European perspective focusing on the coordination of distribution system operator and transmission system operator(DSO-TSO).We pres-ent the insights into the systems used in these control centers and the role of vendors in their *** this paper,we present the perspectives of challenges,operational capabilities,and the involvement of various parties who will be re-sponsible to make the transition *** differences are pointed out on how distribution operations are conducted between the US and Europe.

关键词： Distribution control center(DCC) power system operation distributed generation asset flexibility volt-var optimization and control.

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Improved speciation of dissolved organic nitrogen in natural waters: amide hydrolysis with fluorescence derivatization

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Journal of Environmental Sciences 2008年第10期20卷 1273-1280页

作者： Ryan L.Fimmen Tamara D.Trouts daniel D.Richter jr. Dharni Vasudevan School of Earth Sciences The Ohio State University 125 S.Oval MallColumbus OH 43210 USA.Nicholas School of the Environment and Earth Sciences Duke University Durham NC 27708 USA School of Earth Sciences The Ohio State University 125 S.Oval MallColumbus OH 43210 USA Nicholas School of the Environment and Earth Sciences Duke UniversityDurham NC 27708 USA. Nicholas School of the Environment and Earth Sciences Duke UniversityDurham NC 27708 USA.Department of Chemistry Bowdoin CollegeBrunswick ME 04011 USA

The objective of this study was to improve primary-amine nitrogen (1°-N) quantification in dissolved organic matter (DOM) originating from natural waters where inorganic forms of N, which may cause analytical interference, are commonly encountered. Efforts were targeted at elucidating organic-N structural criteria influencing the response of organic amines to known colorimetric and fluorescent reagents and exploring the use of divalent metal-assisted amide hydrolysis in combination with fluorescence analyse...

关键词： dissolved organic matter/nitrogen (DOM/DON) o-phthaldialdehyde fluorescamine ninhydrin amino acids amide hydrolysis peptides

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Vivid birds do not initiate flight sooner despite their potential conspicuousness

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Current Zoology 2015年第4期61卷 773-780页

作者： Nicholai M. HENSLEY Jonathan P. DRURY Theodore GARLAND, jr. daniel T. BLUMSTEIN Department of Ecology Evolution and Marine Biology University of Califomia Santa Barbara CA USA Department of Ecology and Evolutionary Biology University of California Los Angeles CA 90095-1606 USA Institude de Biologie de I'ENS 46 Rue d'Ulm 75005 Paris France Department of Biology University of California Riverside CA 92521 USA

The distance from an approaching threat at which animals initiate flight - flight-initiation distance （FID） -- is a sensitive metric of variation in risk, but the effects on FID associated with the risk of possessing highly detectable external coloration are unknown. We tested whether variation in the degree of plumage vividness in birds explained variation in flight-initiation distance. After controlling for body mass, the distance at which the experimental approach began, and phylogenetic relatedness, plumage vividness was not a predictor of FID. Contrary to the expectation that vividness affects risk, and therefore risk assess- ment, these results suggest that birds do not compensate for greater visual conspicuousness by fleeing sooner from approaching threats [Current Zoology 61 （4）： 773-780, 2015].

关键词： Antipredator behavior Body size Coloration Comparative method Conspicuousness Flight Initiation Distance

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Takotsubo cardiomyopathy:A comprehensive review

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World Journal of Cardiology 2022年第6期14卷 355-362页

作者： Walker Barmore Himax Patel Sean Harrell daniel Garcia Joe B Calkins jr Department of Internal Medicine Augusta University Medical CenterAugustaGA 30912United States Department of Cardiovascular Medicine Augusta University Medical CenterAugustaGA 30912United States

Takotsubo cardiomyopathy(TCM),also known as stress cardiomyopathy,occurs in the setting of catecholamine surge from an acute *** cardiomyopathy mimics acute myocardial infarction in the absence of coronary *** classic feature of TCM is regional wall motion abnormalities with characteristic ballooning of the left *** etiology of the stressor is often physical or emotional stress,however iatrogenic causes of TCM have been reported in the *** our review,we discuss medications,primarily the exogenous administration of catecholamines,and a wide array of procedures with subsequent development of iatrogenic *** is unique in that it is transient and has favorable outcomes in most ***,beta-blockers and ACE-inhibitors have been prescribed in individuals with cardiomyopathy;however,unique to TCM,no specific treatment is required other than temporary supportive measures as this process is ***,no improvement in mortality or recurrence have been reported in patients on these *** aim of this review is to elucidate on the iatrogenic causes of TCM,allowing for prompt recognition and management by clinicians.

关键词： Takotsubo Cardiomyopathy Iatrogenic Heart Failure Myocardial Infarction

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Dynamic Response of Structure under Blast Load

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Journal of Civil Engineering and Architecture 2016年第4期10卷 421-429页

作者： daniel Makovicka jr. daniel Makovicka Department of Mechanics KIokner Institute Czech Technical University Prague CZ 166 08 Czech Republic Static and Dynamic Consulting Firm Kutna Hora CZ 284 01 Czech Republic

The paper follows from the theory of explosion and interaction of an impact wave formed by the explosion and a structure. Firstly, the paper determines the parameters of the blast wave excited by a small charge explosion. The empirical formulas on the basis of our own experimental results are shown and used for the structure analysis. Evaluations of structures loaded by an explosion based on dynamic response in rotations round the central line of plate or beam systems during the dynamic load of this type is discussed in the paper and comparison of own limit values and published ones is presented. Blast loads typically produce very high strain rates in the range of 102 to 10-4 s-1. The effect of strain rate for concrete material is discussed. The formulas for increased compressive strength of concrete and steel reinforcement are presented. The ductility of structural members is influenced by the corresponding values under high strain rate of reinforcement, Damage to the structure is assessed accordingly firstly by the angle of rotation of the middle axis/surface, and secondly by the limit internal forces of the selected structure. The extreme nature of blast resistance makes it necessary to accept that structural members have some degree of inelastic response in most cases. This enables the application of structure dissipation using the ductility factor and increased of concrete strength. The limits are correlated with qualitative damage expectations. The methodology of dynamic response assessment and its application to the simple bridge structure is discussed.

关键词： Explosion blast wave dynamic load response assumption bridge structure.

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Simulations of a logistic-type model with delays for Chagas disease with insecticide spraying

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International Journal of Biomathematics 2017年第3期10卷 41-60页

作者： Nofe Al-Asuoad Tyler Pleasant Meir Shillor Hrishikesh Munugala daniel J. Coffield jr. Anna Maria Spagnuolo Department of Mathematics and Statistics Oakland University Rochester MI 48309 USA Harrison High School MI USA Novi High School Novi MI 48375 USA Mathematics Department University of Michigan-Flint Flint MI 48502 USA

This work studies and numerically simulates a logistic-type model for the dynamics of Chagas disease, which is caused by the parasite T. cruzi and affects millions of humans and domestic mammals throughout rural areas in Central and South America. A basic model for the disease dynamics that includes insecticide spraying was developed in Spagnuolo et al. （2010） [271 and consists of a delay-differential equation for the vectors and three nonlinear ordinary differential equations for the populations of the infected vectors, infected humans and infected domestic mammals. In this work, the vector equation is modified by using a logistic term with zero, one or two delays or time lags. The aim of this study is three-fold： to numerically study the effects of using different numbers of delays on the model behavior; to find if twice yearly insecticide spraying schedules improve vector control; and to study the sensitivity of the system to the delays in the case of two delays, by introducing randomness in the delays. It is found that the vector equation with different number of delays has very different solutions. The ＂best＂ day of spraying is the middle of Spring and twice annual sprayings cause only minor improvements in disease control. Finally, the model is found to be insensitive to the values of the delays, when the delays are randomly distributed within rather narrow intervals or ranges centered on the parameter values used in Coffield et al. （2014） [8].

关键词： Chagas disease logistic equation with delays epidemic dynamics nonlinear dynamical system simulations.

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