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A Comprehensive Overview of Skeletal Phenotypes Associated with Alterations in Wnt/β-catenin Signaling in Humans and Mice

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Bone Research 2013年第1期1卷 27-71页

作者： Kevin A.Maupin casey j.droscha Bart O.Williams Program for Skeletal Pathobiology and Center for Tumor Metastasis Van Andel Research Institute333 Bostwick NEGrand RapidsMI 49503USA

The Wnt signaling pathway plays key roles in differentiation and development and alterations in this signaling pathway are causally associated with numerous human diseases. While several laboratories were examining roles for Wnt signaling in skeletal development during the 1990s, interest in the pathway rose exponentially when three key papers were published in 2001-2002. One report found that loss of the Wnt co-receptor, Low-density lipoprotein related protein-5 （LRPS）, was the underlying genetic cause of the syndrome Osteoporosis pseudoglioma （OPPG）. OPPG is characterized by early-onset osteoporosis causing increased susceptibility to debilitating fractures. Shortly thereafter, two groups reported that individuals carrying a specific point mutation in LRP5 （G171V） develop high-bone mass. Subsequent to this, the causative mechanisms for these observations heightened the need to understand the mechanisms by which Wnt signaling controlled bone development and homeostasis and encouraged significant investment from biotechnology and pharmaceutical companies to develop methods to activate Wnt signaling to increase bone mass to treat osteoporosis and other bone disease. In this review, we will briefly summarize the cellular mechanisms underlying Wnt signaling and discuss the observations related to OPPG and the high-bone mass disorders that heightened the appreciation of the role of Wnt signaling in normal bone development and homeostasis. We will then present a comprehensive overview of the core components of the pathway with an emphasis on the phenotypes associated with mice carrying genetically engineered mutations in these genes and clinical observations that further link alterations in the pathway to changes in human bone.

关键词： Wnt signaling mouse models Lrp5/Lrp6 -catenin skeletal phenotypes

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^(99m)TC-Methylene diphosphonate uptake at injury site correlates with osteoblast differentiation and mineralization during bone healing in mice

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Bone Research 2015年第2期3卷 92-99页

作者： Zhendong A Zhong Anderson Peck Shihong Li jeff Van Oss john Snider casey j droscha Tingtung A Chang Bart O Williams Center for Skeletal Disease Research Van Andel Research Institute Department of Internal Medicine Center for Musculoskeletal Health UC Davis Medical Center Small Animal Imaging Facility Van Andel Research Institute

99mTc-Methylene diphosphonate （99mTc-MDP） is widely used in clinical settings to detect bone abnormalities. However, the mechanism of 99mTc-MDP uptake in bone is not well elucidated. In this study, we utilized a mouse tibia injury model, single-photon emission computed tomography （gamma scintigraphy or SPECT）, ex vivo micro-computed tomography, and histology to monitor 99mTc-MDP uptake in injury sites during skeletal healing. In an ex vivo culture system, calvarial cells were differentiated into osteoblasts with osteogenic medium, pulsed with 99mTc-MDP at different time points, and quantitated for 99mTc-MDP uptake with a gamma counter. We demonstrated that 99mTc-MDP uptake in the injury sites corresponded to osteoblast generation in those sites throughout the healing process. The 99mTc-MDP uptake within the injury sites peaked on day 7 post-injury, while the injury sites were occupied by mature osteoblasts also starting from day 7. ~mTc-MDP uptake started to decrease 14 days post-surgery, when we observed the highest level of bony tissue in the injury sites. We also found that 99mTc-MDP uptake was associated with osteoblast maturation and mineralization in vitro. This study provides direct and biological evidence for 99mTc-MDP uptake in osteoblasts during bone healing in vivo and in vitro.

关键词： MDP bone TC-Methylene diphosphonate uptake at injury site correlates with osteoblast differentiation and mineralization during bone healing in mice SPECT

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Development of donor specific antibodies after SARS-CoV-2 vaccination:What do we know so far?

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World journal of Meta-Analysis 2024年第2期12卷 1-4页

作者： Ahmed Daoud Karim Soliman Maria Aurora Posadas Salas Sakshi Vaishnav Genta Uehara AhmedAbdelkader Tibor Fulop Michael j casey Department of Medicine Division of NephrologyMedical University of South CarolinaCharlestonSC 29425United States Department of Medicine Cairo University Medical SchoolCairo 11211Egypt Department of Medicine Medical ServicesRalph H.Johnson VA Medical CenterCharlestonSC 29425United States Department of Medicine Division of NephrologyMedical ServicesRalph H.Johnson VA Medical CenterCharlestonSC 29425United States

Vaccination against Coronavirus disease-19(COVID-19)was pivotal to limit spread,morbidity and *** aim is to find out whether vaccines against COVID-19 lead to an immunological response stimulating the production of de novo donor specific antibodies(DSAs)or increase in mean fluorescence intensity(MFI)of pre-existing DSAs in kidney transplant recipients(KTRs).This study involved a detailed literature search through December 2nd,2023 using PubMed as the primary *** search strategy incorporated a combination of relevant Medical Subject Headings terms and keywords:"COVID-19","SARS-CoV-2 Vaccination","Kidney,Renal Transplant",and"Donor specific antibodies".The results from related studies were collated and analyzed.A total of 6 studies were identified,encompassing 460 KTRs vaccinated against *** responses were detected in 8 KTRs of which 5 had increased MFIs,1 had de novo DSA,and 2 were categorized as either having de novo DSA or increased *** were 48 KTRs with pre-existing DSAs prior to vaccination,but one study(Massa et al)did not report whether pre-existing DSAs were associated with post vaccination *** the remaining 5 studies,35 KTRs with pre-existing DSAs were identified of which 7 KTRs(20%)developed de novo DSAs or increased ***,no immunological response was detected in 452(98.3%)*** study affirms prior reports that COVID-19 vaccination is safe for KTRs,especially if there are no pre-existing ***,if KTRs have pre-existing DSAs,then an increased immunological risk may be *** findings need to be taken cautiously as they are based on a limited number of patients so further studies are still needed for confirmation.

关键词： COVID-19 SARS-CoV-2 vaccination Kidney Renal transplant Donor specific antibodies

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Effect of ethanol on pro-apoptotic mechanisms in polarizedhepatic cells

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World journal of Gastroenterology 2007年第37期13卷 4960-4966页

作者： Benita L McVicker Dean j Tuma Carol A casey Liver Study Unit Department of Veterans Affairs Medical Center and Departments of Internal Medicine and Biochemistry & Molecular Biology University of Nebraska Medical Center Omaha NE 68105 United States

Chronic ethanol consumption is associated with serious and potentially fatal alcohol-related liver injuries such as hepatomegaly, alcoholic hepatitis and cirrhosis. Moreover, it has been documented that the clinical progression of alcohol-induced liver damage may be associated with an increase in hepatocellular death that involves apoptotic mechanisms. Although much information has been learned about the clinical manifestations associated with alcohol-related diseases, the search continues for a better understanding of the molecular and/or cellular mechanisms by which ethanol exerts its deleterious effects such as the induction of pro-apoptotic mechanisms and related cell damaging events. As part of the effort to enhance our understanding of those particular cellular pathways and mechanisms associated with ethanol toxicity, researchers over the years have utilized a variety of model systems. Recently, work has come forth demonstrating the utility of a hybrid cell line (WIF-B) as a cell culture model system for the study of alcohol-associated alterations in hepatocellular mechanisms. Success with such emerging model systems could aid in the development of potential therapeutic treatments for the prevention of alcohol- induced apoptotic cell death that may ultimately serve as a significant target in delaying the onset and/or progression of clinical symptoms of alcohol-mediated liver disease. This review article summarizes the current understanding of ethanol-mediated modifications in cell survival and thus the promotion of pro-apoptotic events with emphasis on analyses made in various experimental model systems, particularly the more recently characterized WIF-B cell system.

关键词： Hepatoma hybrid cells Ethanol Apoptosis Fas receptor Caspase

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Kinematic analysis of penile reflexes in a rat model of spinal cord injury

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Asian journal of Andrology 2021年第1期23卷 30-35页

作者： casey j Steadman Sai S Vangoor Charles H Hubscher Department of Anatomical Sciences and Neurobiology University of LouisvilleLouisvilleKY 40202USA Kentucky Spinal Cord Injury Research Center LouisvilleKY 40202USA.

The ex-copula penile dorsiflexion reflex(PDFR)is an established measure of sexual dysfunction in male rat models of spinal cord *** the PDFR after complete spinal transection is well described,information regarding the more clinically relevant incomplete spinal contusion injury model is *** study examined,using two-dimensional(2D)kinematic analysis,the relationship between the PDFR and degree of white matter sparing(WMS).Male Wistar rats received a T9 contusion with varying degrees of impactor *** kinematic recordings of the PDFR were made 3-8 weeks *** reflex components examined included maximum angle of penile dorsiflexion,total penile event duration,and penile ascent *** hoc comparison between animals grouped based upon injury severity(moderate-severe:13.33%-17.15%WMS vs moderate:20.85%-33.50%WMS)ndicated PDFR ***,the numbers of animals with more moderate contusions having data points above the median n both maximum angle of penile dorsiflexion and penile ascent speed were significantly lower than animals with more severe *** penile event duration was also affected but only at more chronic time points(6-8 weeks).Thus,2D kinematic analysis of the PDFR allows for more consistent and quantifiable analysis of the subtle differences that can occur between injury severity groups in the rat contusion model.

关键词： erection penile sexual dysfunction spinal cord injury

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Should we have a guard against therapeutic nihilism for patients with severe traumatic brain injury?

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Neural Regeneration Research 2017年第11期12卷 1801-1803页

作者： Ryan Hirschi casey Rommel Gregory W.j.Hawryluk School of Medicine University of UtahSalt Lake CityUTUSA Department of Biomedical Informatics School of MedicineUniversity of UtahSalt Lake CityUTUSA Department of Neurological Surgery University of UtahClinical Neurosciences CenterSalt Lake CityUTUSA

Many clinicians would agree that a vegetative outcome is a fate worse than death after a severe traumatic brain injury （TBI）. In an effort to avoid poor outcomes of this nature, neurotrauma practitioners draw from their training and experience to make the monumental decision of when to recommend against aggressive care in severe TBI patients. Such judgements are,

关键词： guard against therapeutic evere traumatic

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Synchronous formation of the‘forearc’Bay of Islands ophiolite and its basal high-temperature metamorphic sole constrained by U-Pb zircon ages

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Geoscience Frontiers 2023年第6期14卷 234-272页

作者： Weiyao Yan john F.casey Department of Earth and Atmospheric Sciences University of HoustonHoustonTXUSA

The welded metamorphic sole at the base of the Bay of Islands Ophiolite Complex(BOIC)in the Northern Appalachians of Newfoundland shows a typical inverted pressure-temperature(P-T)metamorphic gradient from HT-MP granulite to LT-LP greenschist *** incorporates mafic volcanic/plutonic protoliths mixed with pelagic,hemi-pelagic and coarser epiclastic sedimentary *** LA-ICP-MS U–Pb concordia ages,trace elements,and Ti-in-zircon geothermometry for -250 zircon analyses from three metabasites of the upper HT sole amphibolites with N-MORB-like protoliths are *** samples collected within meters of the ophiolite peridotite-sole contact of the Blow Me Down Mountain and North Arm Mountain massifs yielded the oldest comparable concordia ages of 487.7±2.6 Ma and 489.1±3.1 Ma,respectively,that are both within error of the igneous age of 488.3±1.5 Ma of the directly overlying BOIC ophiolite,which formed at a supra-subduction zone(SSZ)forearc spreading center.A third slightly younger age of 484.2±2.4 Ma was obtained for an upper HT amphibolite sample with similar phase assemblages but collected30 m below the peridotite contact of the Table Mountain *** crystals analyzed have similar size and morphologies,subparallel rare earth element(REE)variation patterns,and steep heavy REE-enrichments((Lu/Gd)_(cn)>20),significant positive Ce anomalies(dominantly>5)and slight positive to dominantly negative Eu anomalies(1.2–0.4).Zircon shows Th/U mean values of 0.37–0.48 with little to no rim to core *** Ti-in-zircon mean crystallization temperatures range from764–787℃.These neocrystallized zircon crystals appear to be derived from thin leucosomes within the three *** other samples also from the upper HT sole show evidence of inherited detrital zircon with core dates spanning the Cambrian Notre Dame Arc through older Laurentian-like basement and rift age *** of the sole took place below a hot forearc asthenospheric wed

关键词： Ophiolite metamorphic sole U-Pb zircon ages Hot subduction interface Supra-subduction forearc spreading center Arc-continent collision Taconic Orogeny

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改写恐惧,拯救青春期焦虑

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环球科学 2024年第13期 64-69页

作者： Bj·凯西海蒂·迈耶林颖(翻译) 盛文哲(翻译) 美国巴纳德学院美国波士顿大学系统神经科学中心不详

有关大脑发育和行为发展的研究,为帮助治疗患有常见焦虑及相关障碍的青少年,提供了新的方法。青春期是人类发育和学习的重要时期。在这个阶段,青少年会开始探索自己的社交世界,适应其中所发生的种种变化,逐渐形成对自己身份的认同感,拥... 详细信息

有关大脑发育和行为发展的研究,为帮助治疗患有常见焦虑及相关障碍的青少年,提供了新的方法。青春期是人类发育和学习的重要时期。在这个阶段,青少年会开始探索自己的社交世界,适应其中所发生的种种变化,逐渐形成对自己身份的认同感,拥有理想和抱负。也是在这个阶段,他们会从对父母(或其他照顾者)的依赖过渡到相对独立的状态,首次展示出特定的认知和情感需求,以及对生理变化、社交和性等方面的惊人适应力。不幸的是,该阶段也是绝大多数心理健康问题爆发的高峰期。

关键词：大脑发育青春期适应力社交世界生理变化照顾者青少年心理健康问题

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The role of emergency incident type in identifying first responders' health exposure risks

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journal of Safety Science and Resilience 2023年第2期4卷 167-173页

作者： Emily j.Haas Katherine N.Yoon Alexa Furek Megan casey Susan M.Moore National Personal Protective Technology Laboratory(NPPTL) National Institute for Ocupational Safety and Health(NIOSH)PittsburghPA 15236United States National Personal Protective Technology Laboratory(NPPTL) National Institute forOccupational Safety and Health(NIOSH)MorgantownWV2605United States

Fire-based emergency management service(EMS)personnel are dispatched to various incidents daily,many of which have unique occupational *** fully understand the variability of incident types and how to best pre-pare and respond,an exploration of the *** system of incident types is *** study uses potential exposure to SARS-CoV-2 as a case example to understand if and how coding categories for incident call types may be updated to improve data standardization and emergency response decision *** received emergency response incident data generated by three fire department computer-aided dispatch(CAD)systems between March and September *** incident was labeled EMS,Fire,or *** the 162,766 incidents,approximately 8.1%(n=13,144)noted potential SARS-CoV-2 exposure within their narrative descriptions of which 86.3%were coded as EMS,9.9%as Fire,and 3.9%as *** assess coding variability across incident types,researchers used the original 3-incident type variable and a new 5-incident type variable reassigned by researchers into EMS,Fire,Other,Hazmat,and Motor *** regressions compared differences in potential exposure using the 3-and 5-incident type *** evaluating the 3-incident type variable,those respond-ing to a Fire versus an EMS incident were 84%less likely to be associated with potential exposure to *** the 5-incident type variable,those responding to Fire incidents were 77%less likely to be associated with a potential exposure than those responding to EMS *** in potential exposure between the 3-and 5-incident type models show the need to understand how incident types are *** demonstrates the need for data standardization to accurately categorize incident types to improve emergency preparedness and *** have implications for incident type coding at fire department municipality and national levels.

关键词： Emergencymedical se Firefighter Incident type Surveillance Telecommunicator

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No association between cyclooxygenase-2 and uridine diphosphate glucuronosyltransferase 1A6 genetic polymorphisms and colon cancer risk

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World journal of Gastroenterology 2009年第18期15卷 2240-2244页

作者： Cheryl L Thompson Sarah j Plummer Alona Merkulova Iona Cheng Thomas C Tucker Graham casey Li Li Departments of Family Medicine and Epidemiology and Biostatistics Case Centerfor Transdisciplinary Research on Energetics and CancerCase Comprehensive Cancer Center Case Western Reserve University. Cleveland OH 44106-7136 United States Department of Preventive Medicine University of Southern California Los Angeles CA90033-1006 United States Department of Cancer Biology Cleveland Clinic Foundation Cleveland OH 44195-0001 United States Department of Epidemiology and Biostatisticsand Institute for Human Genetics University of California SanFrancisco San Francisco CA 94143-0644 United States Markey Cancer Center University of Kentucky Lexington KY 40504-3381 United States

AIM：To investigate the association of variations in the cyclooxygenase-2 （COX2） and uridine diphosphate glucuronosyltransferase 1A6 （UGTIA6） genes and non-steroidal anti-inflammatory drugs （NSAIDs） use with risk of colon ***： NSAIDs, which are known to reduce the risk of colon cancer, act directly on COX2 and reduce its activity. Epidemiological studies have associated variations in the COX2 gene with colon cancer risk, but others were unable to replicate this finding. Similarly,enzymes in the UGT1A6 gene have been demonstrated to modify the therapeutic effect of NSAIDs on colon adenomas. Polymorphisms in the UGTIA6 gene have been statistically shown to interact with NSAID intake to influence risk of developing colon adenomas, but not colon cancer. Here we examined the association of tagging single nucleotide polymorphisms （SNPs） in the COX2 and UGTIA6 genes, and their interaction with NSAID consumption, on risk of colon cancer in a population of 422 colon cancer cases and 481 population ***： No SNP in either gene was individually statistically significantly associated with colon cancer, nor did they statistically significantly change the protective effect of NSAID consumption in our sample. Like others, we were unable to replicate the association of variants in the COX2 gene with colon cancer risk （P 〉 0.05）,and we did not observe that these variants modify the protective effect of NSAIDs （P 〉 0.05）. We were able to confirm the lack of association of variants in UGT1A6 with colon cancer risk, although further studies will have to be conducted to confirm the association of these variants with colon ***： Our study does not support a role of COX2 and UGTIA6 genetic variations in the development of colon cancer.

关键词： Uridine diphosphate glucuronosyltransferase 1A6 Cyclooxygenase-2 Non-steroidal anti-inflammatorydrugs Colon cancer Genetic association studies Singlenucleotide polymorphisms

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