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Predicting disruptions to drug pharmacokinetics and the risk of adverse drug reactions in nonalcoholic steatohepatitis patients

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Acta Pharmaceutica Sinica B 2023年第1期13卷 1-28页

作者： Solène Marie Kayla L.Frost Raymond K.Hau Lucy Martinez-Guerrero Jailyn M.Izu Cassandra M.myers Stephen H.Wright Nathan J.Cherrington College of Pharmacy Department of Pharmacology&ToxicologyUniversity of ArizonaTucsonAZ 85721USA College of Medicine Department of PhysiologyUniversity of ArizonaTucsonAZ 85724USA

The liver plays a central role in the pharmacokinetics of drugs through drug metabolizing enzymes and ***-alcoholic steatohepatitis(NASH)causes disease-specific alterations to the absorption,distribution,metabolism,and excretion(ADME)processes,including a decrease in protein expression of basolateral uptake transporters,an increase in efflux transporters,and modifications to enzyme *** can result in increased drug exposure and adverse drug reactions(ADRs).Our goal was to predict drugs that pose increased risks for ADRs in NASH *** research identified 71 drugs with reported ADRs in patients with liver disease,mainly non-alcoholic fatty liver disease(NAFLD),54 of which are known substrates of transporters and/or metabolizing *** NASH is the progressive form of NAFLD but is most frequently undiagnosed,we identified other drugs at risk based on NASH-specific alterations to ADME ***,we present another list of 71 drugs at risk of pharmacokinetic disruption in NASH,based on their transport and/or metabolism *** encompasses drugs from various pharmacological classes for which ADRs may occur when used in NASH patients,especially when eliminated through multiple pathways altered by the ***,these results may inform clinicians regarding the selection of drugs for use in NASH patients.

关键词： Non-alcoholic steatohepatitis Hepatic elimination Transporter Enzyme Pharmacokinetics Drug-drug interaction Liver Adverse drug reaction

Anesthesia for fetal intervention and surgery /

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Colorectal cancer susceptibility loci associate with disease prognosis

2005年

作者： myers Laura B.

来源：畅想之星图书光盘版（南... 评论

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Colorectal cancer susceptibility loci associate with disease...

Spatial Interpolation of Tidal Data Using a Multiple-Order Harmonic Equation for Unstructured Grids

2010’全国肿瘤分子标志及应用学术研讨会暨第五届中国中青年肿瘤专家论坛

作者： Ronald E.myers Terry Hyslop Division of Population Science Department of Medical OncologyDivision of BiostatisticsDepartment of Pharmacology and Experimental TherapeuticsThomas Jefferson UniversityPhiladelphiaPA 19107U.S.A.

Extensive evidence has suggested that risk factors of cancer development may also modulate the clinical outcome of the same *** genome-wide association (GWA) studies have identified several single nucleotide polymorph...

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International Journal of Geosciences 2013年第10期4卷 1425-1437页

作者： Lei Shi Kurt W. Hess Edward P. myers 1Coast Survey Development Laboratory NOAA Silver Spring USA 2Chesapeake Research Consortium Edgewater USA 1Coast Survey Development Laboratory NOAA Silver Spring USA 2Earth Resources Technology Laurel USA Coast Survey Development Laboratory NOAA Silver Spring USA

A general spatial interpolation method for tidal properties has been developed by solving a partial differential equation with a combination of different orders of harmonic operators using a mixed finite element method. Numerically, the equation is solved implicitly without iteration on an unstructured triangular mesh grid. The paper demonstrates the performance of the method for tidal property fields with different characteristics, boundary complexity, number of input data points, and data point distribution. The method has been successfully applied under several different tidal environments, including an idealized distribution in a square basin, coamplitude and cophase lines in the Taylor semi-infiite rotating channel, and tide coamplitude and cophase lines in the Bohai Sea and Chesapeake Bay. Compared to Laplace’s equation that NOAA/NOS currently uses for interpolation in hydrographic and oceanographic applications, the multiple-order harmonic equation method eliminates the problem of singularities at data points, and produces interpolation results with better accuracy and precision.

关键词： Tides Tidal Data Approximation Harmonic Functions Finite Element Method Spatial Interpolation Taylor Basin Bohai Sea Chesapeake Bay

PERIOPERATIVE STROKE AFTER CAROTID ENDARTERECTOMY ETIOLOGICAL RISK FACTORS AND MANAGEMENT

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Chinese Medical Journal 1994年第6期 62-65页

作者：叶建荣 K.A.myers D.F.Scott T.J.Devine C.Flanc

291 patients were subjected to carotid endarterectomy from January 1985 to June 1992 in two Australian medical institutions. Of the 291 patients, perioperative stroke occurred in 22 (6.3%) after 347 operations (moderate 17 and severe 5). The 22 patients were studied with Doppler scan, angiography, reexploration and CT. Reexploration showed that 12 of 14 patients had thrombosis in the internal carotid artery at operation. The etiological factors for perioperative strokes included thrombosis at the operative sites in 14 patients (64%), cerebral embolism after operation in 4, clamping ischemia in 2, intracerebral hemorrhage in 1 and unknown cause in 1. Six patients (27%) recovered completely in 4 weeks, 10 (45%) had mild residual neurological deficits, 5 (23%) had moderate neurological deficits and 1 died 3 days after operation. Only 6 patients had permanent neurological deficits (6 / 347, 17%).

关键词： In PERIOPERATIVE STROKE AFTER CAROTID ENDARTERECTOMY ETIOLOGICAL RISK FACTORS AND MANAGEMENT

Role of ESR Pathway Genes in Breast Cancer: A Review

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Advances in Breast Cancer Research 2018年第2期7卷 134-186页

作者： Deepak Kumar Marilyn Rae myers Ussama Al Homsi Valentin Ilyin Computational Biology Carnegie Mellon University in Qatar (CMU-Q) Doha Qatar Pennsylvania State University University Park USA Hematology and Oncology Department NCCCR Hamad Medical Corporation Doha Qatar

Breast cancer is the leading cause of death in women. Prognosis of breast cancer is often pessimistic because the tumors are prone to metastasizing to the bone, brain, and lung. The estrogen signaling receptor (ESR) pathway contains 39 main genes and proteins which makes it one of the larger signaling pathways. Predominately this pathway and the proteins within are involved in breast growth and development, making it a prospective area of study for breast cancer. While the healthy ESR pathway has been constructed and is well established, a mechanistic model of mutated genes of ESR pathway has not been delved upon. Such mutated models could be utilized for selecting combinational targets for drug therapies, as well as elucidating crosstalk between other pathways and feedback mechanisms. To construct the mutated models of the ESR pathway it is imperative to assess what is currently understood in the literature and what inconsistencies exist in order to resolve them. Without this information, a model of the ESR pathway will be unreliable and likely unproductive. This review is the detailed literature survey of the biological studies performed on ESR pathways genes, and their respective roles in breast cancer. Furthermore, the details mentioned in the review can be beneficial for the integrated study of the ESR pathway genes, which includes, structural and dynamics study of the genes products, to have a holistic understanding of the cancer mechanism.

关键词： Estrogen Signaling Receptor (ESR) Pathway Breast Cancer ESR Genes Mechanistic Modeling Integrated Study Kyoto Encyclopedia of Genes and Genomes (KEGG) PubMed Literature Survey

Upper-gastrointestinal bleeding secondary to peptic ulcer disease:Incidence and outcomes

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World Journal of Gastroenterology 2014年第46期20卷 17568-17577页

作者： Samuel Quan Alexandra Frolkis Kaylee Milne Natalie Molodecky Hong Yang Elijah Dixon Chad G Ball Robert P myers Subrata Ghosh Robert Hilsden Sander Veldhuyzen van Zanten Gilaad G Kaplan Departments of Medicine University of CalgaryCalgary T2N-4N1AlbertaCanada Departments of Community Health Sciences Calgary T2N-4N1AlbertaCanada Departments of Surgery University of CalgaryCalgary T2N-4N1AlbertaCanada Department of Medicine University of AlbertaEdmonton T6G-2R7AlbertaCanada

AIM: To evaluate the incidence, surgery, mortality, and readmission of upper gastrointestinal bleeding (UGIB) secondary to peptic ulcer disease (PUD).

关键词： Epidemiology Peptic ulcer hemorrhage Digestive system surgical procedures Mortality Endoscopy Validation studies Incidence

Short-duration transient visual evoked potentials and color reflectivity discretization analysis in glaucoma patients and suspects

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International Journal of Ophthalmology(English edition) 2017年第2期10卷 254-261页

作者： Michael Waisbourd Rebekah H.Gensure Ardalan Aminlari Sonya B.Shah Nitasha Khanna Neil Sood Jeanne Molineaux Alberto Gonzalez Jonathan S.myers L.Jay Katz Wills EyeHospital Glaucoma Research Center PhiladelphiaPA 19107USA Diopsys Inc. Pine BrookNJ 07058USA

AIM： To evaluate the use of short-duration transient visual evoked potentials（VEP） and color reflectivity discretization analysis（CORDA） in glaucomatous eyes,eyes suspected of having glaucoma,and healthy ***： The study included 136 eyes from 136 subjects： 49 eyes with glaucoma,45 glaucoma suspect eyes,and 42 healthy *** underwent Humphrey visual field（VF） testing,VEP testing,as well as peripapillary retinal nerve fiber layer optical coherence tomography imaging studies with post-acquisition CORDA *** analysis was performed using means and ranges,ANOVA,post-hoc comparisons using Turkey＇s adjustment,Fisher＇s Exact test,area under the curve,and Spearman correlation ***： Parameters from VEP and CORDA correlated significantly with VF mean deviation（MD）（P〈0.05）.In distinguishing glaucomatous eyes from controls,VEP demonstrated area under the curve（AUC） values of 0.64-0.75 for amplitude and 0.67-0.81 for *** CORDA HR1 parameter was highly discriminative for glaucomatous eyes vs controls（AUC=0.94）.CONCLUSION： Significant correlations are found between MD and parameters of short-duration transient VEP and CORDA,diagnostic modalities which warrant further consideration in identifying glaucoma characteristics.

关键词： short-duration transient visual evoked potentials optical coherence tomography color reflectivity discretization analysis glaucoma

Proton-pump inhibitor use does not affect semen luality in subfertile men

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Asian Journal of Andrology 2018年第3期20卷 290-293页

作者： Sorena Keihani James R Craig Chong Zhang Angela P Presson Jeremy B myers William O Brant Kenneth I Aston Benjamin R Emery Timothy G Jenkins Douglas T Carrell James M Hotaling Division of Urology Department of Surgery University of Utah Salt Lake City Utah 84132 USA Division of Epidemiology Department of Internal Medicine University of Utah Salt Lake City Utah 84132 USA Andrology and IVF Laboratory Department of Surgery (Urology) University of Utah Salt Lake City Utah 84108 USA

Proton-pump inhibitors （PPIs） are among the most widely used drugs worldwide. PPI use has recently been linked to adverse changes in semen quality in healthy men; however, the effects of PPI use on semen parameters remain largely unknown specifically in cases with male factor infertility. We examined whether PPI use was associated with detrimental effects on semen parameters in a large population of subfertile men. We retrospectively reviewed data from 12 257 subfertile men who had visited our fertility clinic from 2003 to 2013. Patients who reported using any PPIs for 〉3 months before semen sample collection were included; 7698 subfertile men taking no medication served as controls. Data were gathered on patient age, medication use, and conventional semen parameters; patients taking any known spermatotoxic medication were excluded. Linear mixed-effect regression models were used to test the effect of PPI use on semen parameters adjusting for age. A total of 248 patients （258 samples） used PPIs for at least 3 months before semen collection. In regression models, PPI use （either as the only medication or when used in combination with other nonspermatotoxic medications） was not associated with statistically significant changes in semen parameters. To our knowledge, this is the largest study to compare PPI use with semen parameters in subfertile men. Using PPIs was not associated with detrimental effects on semen quality in this retrospective study.

关键词： infertility proton-pump inhibitors semen analysis sperm quality spermatozoa