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Review of clinically Relevant Drug Interactions with Next Generation Hepatitis c Direct-acting Antiviral Agents

Journal of clinical and Translational Hepatology 2020年第3期8卷 322-335页

作者： Jenny Hong robert c.wright Nilu Partovi Eric M.Yoshida Trana Hussaini Pharmaceutical Sciences Vancouver General HospitalVancouverBCCanada Faculty of Pharmaceutical Sciences University of British ColumbiaVancouverBCCanada Liver Transplant Program Vancouver General HospitalVancouverBCCanada Division of Gastroenterology Faculty of MedicineUniversity of British ColumbiaVancouverBCCanada

In this review,we examine the pharmacokinetics and clinically relevant drug interactions of the newer generation direct-acting antivirals(DAAs)for the treatment of chronic hepatitis c,specifically sofosbuvir/velpatasvir(Epclusa®),sofosbuvir/velpatasvir/voxilaprevir(Vosevi®),glecaprevir/pibrentasvir(Maviret®),and elbasvir/grazoprevir(Zepatier®).We searched MEDLINE(1948-January 2020),Embase(1964-January 2020),Google,and GoogleScholar using the terms pharmacokinetics,drug interaction,drug metabolism,sofosbuvir,velpatasvir,Epclusa,voxilaprevir,Vosevi,glecaprevir,pibrentasvir,Maviret,elbasvir,grazoprevir,and Zepatier,from inception to January 13,*** search was limited to randomized controlled trials,in vitro studies,prospective and retrospective human studies,drug monographs,abstracts,and conference *** relevant published literature on pharmacokinetic and pharmacodynamic interactions involving DAAs were reviewed and the data *** clinically relevant drug-drug interactions(DDIs)were identified with the newer generation DAAs and commonly prescribed ***3/4A protease inhibitors are more likely to be involved in DDIs,followed by NS5A inhibitors and NS5B polymerase *** majority of clinically relevant DDIs are predictable,according to known pharmacokinetic,pharmacodynamics,and physicochemical properties of DAAs;however,in select cases,unpredictable DDIs do *** expected,many drug interactions exist between newer generation DAAs and commonly prescribed *** the majority of clinically relevant interactions are predictable,many require therapeutic dose adjustment or careful selection of non-interacting *** select cases,severe and unpredictable drug interactions can *** should consult hepatitis c virus pharmacotherapy experts and tertiary drug interaction resources when initiating DAA therapy in patients taking other medications.

关键词： Hepatitis c Drug interactions Pharmacokinetics Direct-acting antiviral agents

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Airway management of a patient with linear immunoglobulin A bullous dermatosis:A case report

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World Journal of clinical cases 2024年第13期12卷 2263-2268页

作者： Olga c Nin robert Hutnik Neil N chheda David Hutchinson Department of Anesthesiology University of Florida College of MedicineGainesvilleFL 32610United States Department of Otolaryngology University of Florida College of MedicineGainesvilleFL 32610United States

BAcKGROUND There is limited literature on managing the airway of patients with linear immunoglobulin A(IgA)bullous dermatosis,a rare mucocutaneous disorder that leads to the development of friable *** clinical decision making is necessary when there is a risk of bleeding into the airway,and a multidisciplinary team approach may lead to decreased patient morbidity during these high-risk scenarios,especially when confronted with an unusual cause for *** SUMMARY A 45-year-old African American female presented to our ambulatory surgical center for right corneal transplantation due to corneal perforation after blunt trauma in the setting of cicatricial conjunctivitis and diffuse corneal neovascularization from linear IgA bullous *** diagnosis of IgA dermatosis was recent,and the patient had been lost to *** severity of the disease and extent of airway involvement was unknown at the time of the *** airway bleeding was noticed upon intubation and the otorhinolaryngology team had to be called to the operating *** patient required transfer to the intensive care unit where a multidisciplinary team was involved in her *** patient was extubated on postoperative day *** A multidisciplinary approach to treating this disease is the best course of action before a surgical *** our case,key communication between the surgery,anesthesia,and dermatology teams led to the quick and safe treatment of our patient’s *** surgery should not be considered for these cases unless they are in full remission and there is no mucous membrane involvement.

关键词： Airway management Bleeding risk Linear immunoglobulin A bullous dermatosis Multidisciplinary approach Outpatient procedure case report

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Integrins and their potential roles in mammalian pregnancy

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Journal of Animal Science and Biotechnology 2024年第1期15卷 1-19页

作者： Gregory A.Johnson robert c.Burghardt Fuller W.Bazer Heewon Seo Joe W.cain Department of Veterinary Integrative Biosciences School of Veterinary Medicine and Biomedical SciencesTexas A&M UniversityCollege StationTX 77843‑4459USA Department of Animal Science College of Agriculture and Life SciencesTexas A&M UniversityCollege StationTX 77843‑2471USA

Integrins are a highly complex family of receptors that, when expressed on the surface of cells, can mediate reciprocal cell-to-cell and cell-to-extracellular matrix(EcM) interactions leading to assembly of integrin adhesion complexes(IAcs) that initiate many signaling functions both at the membrane and deeper within the cytoplasm to coordinate processes including cell adhesion, migration, proliferation, survival, differentiation, and metabolism. All metazoan organisms possess integrins, and it is generally agreed that integrins were associated with the evolution of multicellularity, being essential for the association of cells with their neighbors and surroundings, during embryonic development and many aspects of cellular and molecular biology. Integrins have important roles in many aspects of embryonic development, normal physiology, and disease processes with a multitude of functions discovered and elucidated for integrins that directly influence many areas of biology and medicine, including mammalian pregnancy, in particular implantation of the blastocyst to the uterine wall, subsequent placentation and conceptus(embryo/fetus and associated placental membranes) development. This review provides a succinct overview of integrin structure, ligand binding, and signaling followed with a concise overview of embryonic development, implantation, and early placentation in pigs, sheep, humans, and mice as an example for rodents. A brief timeline of the initial localization of integrin subunits to the uterine luminal epithelium(LE) and conceptus trophoblast is then presented, followed by sequential summaries of integrin expression and function during gestation in pigs, sheep, humans, and rodents. As appropriate for this journal, summaries of integrin expression and function during gestation in pigs and sheep are in depth, whereas summaries for humans and rodents are brief. Because similar models to those illustrated in Fig. 1, 2, 3, 4, 5 and 6 are present throughout the sc

关键词： Humans Implantation Integrins Pigs Pregnancy Rodents Sheep

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Non-linear dynamic state-space network modeling for decoding neurodegeneration

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Neural Regeneration Research 2024年第9期19卷 1879-1880页

作者： Venkata c.chirumamilla chi Wang Ip Martin Reich robert Peach Jens Volkmann Bahman Nasseroleslami Muthuraman Muthuraman Prenatal Pediatrics Institute Children’s National HospitalWashingtonDCUSA Neural Engineering with Signal Analytics and Artificial Intelligence Department of NeurologyUniversity of WürzburgWürzburgGermany Academic Unit of Neurology Trinity Biomedical Sciences InstituteTrinity College DublinUniversity of DublinDublinIreland

Neurodegenerative disorders represent a pervasive global health challenge,yet therapeutic options remain conspicuously *** disorders are inherently dynamic processes within the central nervous system,unfolding across distinct sub-stages:initial structural neuronal alterations(sub-stage 1),functional impairment(sub-stage 2),and culminating in neuronal death(sub-stage 3).

关键词： alterations impairment dynamic

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The concept of gene therapy for glaucoma:the dream that has not come true yet

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Neural Regeneration Research 2024年第1期19卷 92-99页

作者： robert Sulak Xiaonan Liu Adrian Smedowski Department of Physiology Faculty of Medical Sciences in KatowiceMedical University of Silesia in KatowiceKatowicePoland Institute of Biotechnology HiLIFEUniversity of HelsinkiHelsinkiFinland GlaucoTech co. KatowicePoland

Gene therapies,despite of being a relatively new therapeutic approach,have a potential to become an important alternative to current treatment strategies in *** glaucoma is not considered a single gene disease,the identified goals of gene therapy would be rather to provide neuroprotection of retinal ganglion cells,especially,in intraocular-pressure-independent *** most commonly reported type of vector for gene delivery in glaucoma studies is adeno-associated virus serotype 2 that has a high tro pism to retinal ganglion cells,res ulting in long-term expression and low immunogenic *** gene thera py studies recruit inducible and genetic animal models of optic neuropathy,like DBA/2J mice model of high-tension glaucoma and the optic nerve *** gene therapy-based neuroprotection of retinal ganglion cells is targeting specific genes translating to growth factors(i.e.,brain derived neurotrophic factor,and its receptor TrkB),regulation of apoptosis and neurodegeneration(i.e.,Bcl-xl,Xiap,FAS system,nicotinamide mononucleotide adenylyl transferase 2,Digit3 and Sarm1),immunomodulation(i.e.,crry,c3 complement),modulation of neuroinflammation(i.e.,e rythropoietin),reduction of excitotoxicity(i.e.,com KIlα)and transcription regulation(i.e.,Max,Nrf2).On the other hand,some of gene therapy studies focus on lowering intra ocular pressure,by impacting genes involved in both,decreasing aqueous humor production(i.e.,aquaporin 1),and increasing outflow facility(i.e.,cOX2,prostaglandin F2a receptor,RhoA/RhoA kinase signaling pathway,MMP1,Myocilin).The goal of this review is to summarize the current stateof-art and the direction of development of gene therapy strategies for glaucomatous neuropathy.

关键词： adeno-associated virus gene editing gene therapy glaucoma IOP lowering IOP-independent mechanisms neuroprotection optic nerve optic neuropathy retinal ganglion cells

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Seismic attribute and well-log analysis for channel characterization in the upper San Andres and Grayburg formations of the Midland Basin,Texas

Energy Geoscience

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Energy Geoscience 2024年第2期5卷 263-278页

作者： Sumit Verma Esra Yalçın Yılmaz Laura Ortiz Sanguino Justin Yandell Miles A.Henderson robert c.Trentham Department of Geosciences The University of Texas Permian BasinOdessaTXUSA School of Geosciences The University of OklahomaNormanOKUSA

The Permian Basin is one of the most prolific,and currently one of the most active,oil and gas basins in the *** Lower Permian strata in the Permian Basin have produced more than 14 billion barrels of oil(BBO),making it the largest volume of hydrocarbon in the *** in the Midland Basin during late Leonardian through early Guadalupian(ca.272e269 Ma)resulted in progradation of shelf edge and ultimately closure of the basin by Middle Permian *** analyzed a merged seismic survey covering parts of the Permian Basin(i.e.,central Basin Platform and Midland Basin)in Andrews,Ector,and Midland counties,*** seismic survey and well logs show the presence of gently dipping(ca.1°)clinoforms in the Upper San Andres and Grayburg Formations on the eastern edge of the central Basin Platform and western Midland *** seismic attributes,curvature,and spectral decomposition identify low sinuosity slope channels oriented north-south,but such channels do not appear beyond the *** shelf edge shifts from north to south during deposition of the Upper San Andres and Grayburg *** identify five basinward shifts noted by the migration of the shelf edge toward the basin center and the presence of channel features along the depositional *** petrophysical analysis indicates that channels cut into carbonate rocks and are filled by siliciclastic sediments;this interpretation is supported by the most negative curvature anomalies along the channel axes caused by the differential compaction between the carbonate and siliciclastic *** are a few channels with a northwest-southeast strike,which matches the direction of the concho Lineament observed by satellite *** observations are consistent with previous interpretations of the northern Midland Basin closure during Middle-Late Permian time.

关键词： Permian shelf carbonate

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Protocol for the development and validation of a clinical measurement tool for fear of disease progression and recurrence in cardiac patients

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chronic Diseases and Translational Medicine 2024年第3期10卷 195-204页

作者： Sarah T.clarke Michael Le Grande Barbara M.Murphy robert Hester Alun c.Jackson Melbourne School of Psychological Sciences University of MelbourneParkvilleVictoriaAustralia Australian centre for Heart Health MelbourneVictoriaAustralia centre on Behavioral Health University of Hong KongPokfulamHong KongChina

Introduction: One in two cardiac patients fear having another heart event or their heart condition getting worse. Research in other chronic illnesses demonstrates that screening for fear of progression and recurrence is vital for adequately addressing such concerns in clinical care. The current project aims to develop and validate a measure for fear of progression and recurrence in cardiac ***: The Fear of cardiac Recurrence and Progression Scale (FcRP) will be developed through a multistep process. An initial item pool will be generated through a review of the literature and existing measures and consultation with and feedback from key informants. The item pool will be tested in a sample of over 250 adults who have ever had an acute coronary event, undergone cardiac surgery, or a chronic cardiac condition. Exploratory factor analysis will be used to identify the underlying factors, and Rasch analysis will be used to reduce the number of items. A short form version of the FcRP will be developed for use as a brief screening tool, informed by clinical relevance and Rasch psychometric ***: While many cardiac patients experience fears related to the progression or recurrence of their illness, there remains the need for a validated tool with which these concerns can be identified and measured. It is expected that the design and validation of the FcRP will aid identification of cardiac patients suffering from clinically significant levels of fear of progression and recurrence and facilitate the design of tailored psychological interventions to target these fears.

关键词： anxiety cardiac anxiety cardiac recovery cardiac rehabilitation depression fear of progression fear of recurrence psychological measurement psychosocial screening

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Does MgSO_(4) protect the preterm brain?Dissecting its role in the pathophysiology of hypoxic ischemic encephalopathy

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Neural Regeneration Research 2024年第9期19卷 1861-1862页

作者： robert Galinsky Laura Bennet Alistair J.Gunn The Ritchie centre Hudson Institute of Medical ResearchMelbourneVICAustralia Department of Obstetrics and Gynaecology Monash UniversityMelbourneVICAustralia Department of Physiology The University of AucklandAucklandNew Zealand

Mitigating preterm encephalopathy continues to be one of the greatest challenges in perinatal *** encephalopathy is associated with high mortality,serious morbidity,and significant socio-economic impacts on the individuals,their families,and public health sectors and welfare systems that last a *** cost of disability associated with preterm brain injury continues to *** of this injury,and disability,would significantly reduce this socioeconomic burden.

关键词： encephalopathy mortality hypoxic

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A general mirror equivalence theorem for coset vertex operator algebras

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Science china Mathematics 2024年

作者： robert McRae Yau Mathematical Sciences center Tsinghua University

We prove a general mirror duality theorem for a subalgebra U of a simple conformal vertex algebra A and its commutant V=comA（U）.Specifically,we assume that A≌⊕i∈IUi×Uias a U×V-module,where the U-modules Uiare simple and distinct and are objects of a semisimple braided ribbon category of U-modules,and the V-modules Viare semisimple and contained in a （not necessarily rigid） braided tensor category of *** also assume U=comA（V）.Under these conditions,we construct a braid-reversed tensor equivalenceτ:UA→VA,where UAis the semisimple category of U-modules with simple objects Ui,i∈I,and VAis the category of V-modules whose objects are finite direct sums of *** particular,the V-modules Viare simple and distinct,and VAis a rigid tensor *** an application,we find a rigid semisimple tensor subcategory of modules for the Virasoro algebra at central charge 13+6p+6p-1,p∈Z 2,which is braided tensor equivalent to an abelian 3-cocycle twist of the category of finite-dimensional ***,the Virasoro vertex operator algebra at central charge 13+6p+6p-1is the PSL2（c）-fixed-point subalgebra of a simple conformal vertex algebra W（-p）,analogous to the realization of the Virasoro vertex operator algebra at central charge 13-6p-6p-1as the PSL2（c）-fixed-point subalgebra of the triplet algebra W（p）.

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commentary on “Why people should run after positive affective experiences instead of health benefits”

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Journal of Sport and Health Science 2024年第4期13卷 451-452页

作者： Ting Wang Jinghua chen robert Schinke Liye Zou Body-Brain-Mind Laboratory School of PsychologyShenzhen UniversityShenzhen 518060China School of Kinesiology and Health Sciences Laurentian UniversitySudburyON P3E 2C6Canada

Maltagliati et al.1 recently highlighted the vital role of affective experiences in promoting physical activity(PA).The authors suggested that positive affective experiences,rather than health benefits,can tip the balance in favor of PA over sedentary *** authors proposed a new formal decision model between PA and sedentary alternatives and reported that when health benefits are the unique reason to action,the costs of PA(e.g.,effort)and the subjective value(SV)of sedentary alternatives(V_(sed))are the main drivers of decision-making processes.

关键词： benefits formal decision

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