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Integrated chromatin and transcriptomic profiling of patient-derived colon cancer organoids identifies personalized drug targets to overcome oxaliplatin resistance

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Genes & Diseases 2021年第2期8卷 203-214页

作者： Kuei-ling Tung Kai-Yuan Chen Marcos Negrete Tianyi Chen Alexias Safi Abed Alhalim Aljamal lingyun Song gregory E.Crawford Shengli Ding David S.Hsu Xiling Shen Department of Biological and Environmental Engineering Cornell UniversityIthacaNY14853USA Department of Biomedical Engineering Pratt School of EngineeringDuke UniversityDurhamNC27708USA Center for Genomics and Computational Biology Duke UniversityDurhamNC27708USA Department of Medical Oncology Duke University Medical CenterDurhamNC27708USA Department of Pediatrics Division of Medical GeneticsDuke UniversityDurhamNC27708USA Duke Cancer Institute Duke UniversityDurhamNC27708USA

Colorectal cancer is a leading cause of cancer *** colorectal cancer patients eventually develop chemoresistance to the current standard-of-care ***,we used patient-derived colorectal cancer organoids to demonstrate that resistant tumor cells undergo significant chromatin changes in response to oxaliplatin *** transcriptomic and chromatin accessibility analyses using ATAC-Seq and RNA-Seq identified a group of genes associated with significantly increased chromatin accessibility and upregulated gene ***/Cas9 silencing of fibroblast growth factor receptor 1(FGFR1)and oxytocin receptor(OXTR)helped overcome oxaliplatin ***,treatment with oxaliplatin in combination with an FGFR1 inhibitor(PD166866)or an antagonist of OXTR(l-368,899)suppressed chemoresistant ***,oxaliplatin treatment did not activate either FGFR1 or OXTR expression in another resistant organoid,suggesting that chromatin accessibility changes are *** use of patient-derived cancer organoids in combination with transcriptomic and chromatin profiling may lead to precision treatments to overcome chemoresistance in colorectal cancer.

关键词： Chromatin accessibility Drug screening Patient-derived organoids Personalized medicine Target discovery

Stool DNA-based versus colonoscopy-based colorectal cancer screening: Patient perceptions and preferences

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Family Medicine and Community Health 2015年第3期3卷 2-8页

作者： Matthew V.Abola Todd F.Fennimore Marcia M.Chen Zhengyi Chen Ashutosh K.Sheth gregory Cooper li li Department of Family Medicine and Community Health Case Western Reserve University School of Medicine11001 Cedar AvenueSuite 200ClevelandOH 44106USA Division of Gastroenterology University Hospitals Case Medical Center11100 Euclid AvenueClevelandOH 44106USA Case Comprehensive Cancer Center Case Western Reserve University School of Medicine10900 Euclid AvenueClevelandOH 44106USA Swetland Center for Environmental Health Case Western Reserve University11000 Cedar AvenueSuite 402ClevelandOH 44106USA

Objective:Stool DNA(sDNA)tests offer a noninvasive form of colon cancer screening for pa-tients,and although the test is expected to increase uptake of colon cancer screening,it is unknown if patients’perceptions of the sDNA test differ according to race and other patient ***:We conducted a self-administered survey of patients undergoing both a colonoscopy and an sDNA test to evaluate perceptions of sDNA ***:Of the 613 participants who were sent surveys,423 responded(69%response rate).Respondents self-identified as African American(n=127,30%),Caucasian(n=284,67%),and other ethnicity(n=12,3%).In general,participants found the sDNA test more suitable than a colonos-copy(n=309,75%).In univariate analyses,a higher percentage of Caucasians as compared with African Americans found the sDNA test more suitable than a colonoscopy(89%vs.76%,pl differences to no significance.A family history of colo-rectal cancer remains a significant factor for patient’s preferences for screening regardless of ***:Our study shows no racial differences in the perception of and preference for sDNA testing for colon *** to increase the uptake of sDNA testing may help reduce racial disparities in colorectal cancer.

关键词： Colon cancer screening race stool DNA test patient perceptions

Formal Safety Assessment of a Marine Seismic Survey Vessel Operation,Incorporating Risk Matrix and Fault Tree Analysis

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Journal of Marine Science and Application 2020年第2期19卷 155-172页

作者： gregory Asuelimen Eduardo Blanco-Davis Jin Wang Zaili Yang Dante Benjamin Matellini Department of Maritime and Mechanical Engineering LOOM Research InstituteLiverpool John Moores UniversityJames Parsons BuildingByrom StreetLiverpool L33AFUK

In maritime safety research,risk is assessed usually within the framework of formal safety assessment(FSA),which provides a formal and systematic methodology to improve the safety of lives,assets,and the environment.A bespoke application of FSA to mitigate accidents in marine seismic surveying is put forward in this paper,with the aim of improving the safety of seismic vessel operations,within the context of developing an economically viable *** work herein takes a close look at the hazards in North Sea offshore seismic surveying,in order to identify critical risk factors,leading to marine seismic survey *** risk factors leading to undesirable events are analysed both qualitatively and quantitatively.A risk matrix is introduced to screen the identified undesirable *** to the screening,Fault Tree Analysis(FTA)is presented to investigate and analyse the most critical risks of seismic survey operation,taking into account the lack of historical *** obtained results show that man overboard(MOB)event is a major risk factor in marine seismic survey operation;lack of training on safe work practice,slippery deck as a result of rain,snow or water splash,sea state affecting human judgement,and poor communication are identified as the critical risk contributors to the MOB ***,the risk control options are focused on the critical risk contributors for ***,suggestions for the introduction and development of the FSA methodology are highlighted for safer marine and offshore operations in general.

关键词： Seismic vessel Formal safety assessment Maritime safety Hazard identification Risk assessment Risk control option Cost-benefit assessment

Systemic evidence of acute seizureassociated elevation in serum neuronal injury biomarker in patients with temporal lobe epilepsy

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Acta Epileptologica 2019年第1期1卷 3-17页

作者： Shailaja Kunda Reghann G.laFrance-Corey Fatemeh Khadjevand gregory A.Worrell Charles l.Howe Department of Neurology Mayo ClinicRochesterMN 55905USA. Translational Neuroimmunology lab Mayo ClinicGuggenheim 15-42C200 First St SWRochesterMN 55905USA. Epilepsy and Neurophysiology lab Mayo ClinicRochesterMN 55905USA. Department of Physiology and Biomedical Engineering Mayo ClinicRochesterMN 55905USA. Center for Multiple Sclerosis and Autoimmune Neurology Mayo ClinicRochesterMN 55905USA.

Background:Patients with drug refractory temporal lobe epilepsy frequently accumulate cognitive impairment over time,suggesting loss of neurons induced by *** objective was to determine whether there is a temporal association between changes in serum levels of neural injury markers and electroencephalographic(EEG)evidence of seizures and interictal ***:We measured serum levels of neuron-specific enolase(NSE),a neuronal injury marker,relative to levels of S100β,a marker of glial injury,at 6 AM,9 AM,noon,3 PM,and 6 PM over the course of several days in 7 epilepsy patients undergoing continuous video-EEG monitoring and in 4 healthy ***:All epilepsy patients exhibited significant deviations in NSE levels through time,and 4 of the epilepsy patients exhibited large sample entropy values and large signal variation metrics for NSE relative to S100β.Controls did not exhibit such *** analysis revealed that NSE levels were significantly elevated after *** was also a highly significant relationship between increased EEG spike frequency and an increase in serum NSE levels measured 24 h ***:The detection of large but transient post-ictal increases in NSE suggests that even self-limited seizures may cause an injury to neurons that underlies cognitive decline in some *** this study used a small patient population,the pilot findings suggest that post-ictal assessment of serum NSE may serve as a biomarker for measuring the efficacy of future acute neuroprotective strategies in epilepsy patients.

关键词： Neuroprotection Neuron-specific enolase Biomarker Temporal lobe epilepsy Entropy Spike frequency

Particle Association of Enterococcus and Total Bacteria in the lower Hudson River Estuary, USA

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Journal of Water Resource and Protection 2011年第10期3卷 715-725页

作者： Elizabeth Suter Andrew R. Juhl gregory D. O’Mullan 不详

Bacterial particle association has important consequences for water-quality monitoring and modeling. Particle association can change vertical and horizontal transport of bacterial cells, as well as patterns of persistence and production. In this study, the abundance and particle association of total bacteria and the fecal-indicator, Enterococcus, were quantified between June and October 2008 in the lower Hudson River Estuary (HRE). Twelve sites were sampled, including mid-channel, near shore, and tributary habitats, plus a sewage outfall. Total bacterial cell counts averaged 9.2 × 109 ± 6.4 × 109 cell l–1 (1 standard deviation), comparable to previous sampling in the HRE. Unlike earlier studies, bacterial abundance did not change consistently along the north/south estuarine salinity gradient. Enterococcus concentrations were highly variable, but mid-channel stations had significantly lower values than other habitat categories. Counts of total bacteria and Enterococcus were both correlated with turbidity, which was also significantly lower at mid-channel stations. A larger fraction of Enterococci were associated with particles (52.9 ± 20.9%, 1 standard deviation) than in the pool of total bacteria (23.8 ± 15.0%). This high frequency of particle association, relative to total bacteria, could cause Enterococcus to be preferentially retained near input sources because of enhanced deposition to bottom sediments, where they would be available for later resuspension. In turn, retention and resuspension in nearshore environments may explain the observed cross-channel variability of turbidity and Enterococcus. Assessments and predictive models of estuarine water quality may be improved by incorporating cross-channel variability and the effects of particle association on key indicators.

关键词： Attachment Fecal Indicator Bacteria Sedimentation Sinking Rate Sewage

A pilot prospective prevalence study of chronic rhinosinusitis associated with inflammatory bowel disease

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World Journal of Otorhinolaryngology-Head and Neck Surgery 2022年第4期8卷 339-344页

作者： India Dhillon Jennifer Ham Ximena Maul gregory Rosenfeld Andrew Thamboo Division of Otolaryngology St.Paul's Sinus CentreUniversity of British ColumbiaVancouverBritish ColumbiaCanada Division of Gastroenterology University of British ColumbiaVancouverBritish ColumbiaCanada

Background:Inflammatory bowel disease(IBD)is characterized by chronic inflammation of the gastrointestinal ***-intestinal manifestations such as pulmonary diseases have been *** rhinosinusitis(CRS),an inflammatory condition of the sinonasal mucosa,has been associated with several lung *** the relationship between lung and intestinal pathologies,and lung and sinus pathologies,we aimed to determine the prevalence of IBD among CRS ***:Pilot prevalence ***-two CRS patients were screened for IBD symptoms from October 2018 to January ***-reported disease symptoms and overall quality of life were evaluated using the Sino-Nasal Outcome Test 22(SNOT-22),Short Inflammatory Bowel Disease Questionnaire(SIBDQ),and EuroQol 5 Dimension 5 level(EQ-5D-5l)*** Modified lund-Kennedy(MlK)endoscopic and lund-Mackay(lM)grading systems were used to confirm CRS *** who reported subjective symptoms of IBD were referred to a gastroenterologist clinic for further ***:Twenty of the 92(20.2%,95%CI:12.6%-29.8%)CRS patients reported symptoms of IBD and four individuals(4.26%,95%CI:1.17%-10.50%)were sub-sequently diagnosed with *** to patients without IBD symptoms(n=72),those with symptoms(n=20)reported significantly worse SNOT-22(P=0.002),SIBDQ(Pl(P=0.0063)***,these patients did not exhibit significantly different MlK(P=0.81)or lM(P=0.04)***:The prevalence of IBD may be elevated among individuals with CRS relative to the general Canadian *** pilot study suggests that CRS with IBD is associated with lower quality of *** cross-sectional studies with larger sample sizes are required.

关键词： chronic rhinosinusitis microbiome Modified lund–Kennedy quality of life Sino-Nasal Outcome Test 22(SNOT-22)

Secondary Prevention Following Coronary Artery Bypass Surgery: A Pilot Study for Improved Patient Education

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International Journal of Clinical Medicine 2012年第4期3卷 286-294页

作者： Jeffrey B. Kramer Patricia A. Howard Brian J. Barnes Bashar Ababneh Purna Mukhopadhyay Mazda Biria gregory F. Muehlebach Emmanuel Daon George l. Zorn William A. Reed James l. Vacek Cardiovascular Division Department of Internal Medicine School of Medicine The University of Kansas Medical Center Kansas City Kansas Cardiovascular Division Department of Internal Medicine School of Medicine.The University of Kansas Medical Center Kansas City Kansas Department of Biostatistics School of Medicinel The University of Kansas Medical Center Kansas City Kansas Department of Pharmacy Practice School of Pharmacy The University of Kansas Medical Center Kansas City Kansas Mid-America Thoracic and Cardiovascular Surgeons The University of Kansas Medical Center Kansas City Kansas Mid-America Thoracic and Cardiovascular Surgeons The University of Kansas Medical Center Kansas City Kansas.

Background: Sustained positive outcomes after coronary artery bypass grafting (CABG) requires risk factor modification and secondary prevention medications. Much attention has been focused on planning at hospital discharge;however longer-term patient compliance is not well described. Hypothesis: A follow-up multidisciplinary educational program improves disease understanding, motivation to reduce cardiovascular risk, and secondary prevention medication prescribing following hospital discharge. Methods: Using a prospective, randomized, controlled design, patients undergoing CABG completed surveys over a year period, assessing disease understanding and motivation. Four to six weeks after CABG, intervention subjects completed a one-time educational program with a multidisciplinary team. The primary endpoint was a composite score of reduced risk factors, medication use, and awareness of prescribed medications. Secondary endpoints evaluated survey scores and medication use rates. Wilcoxon Rank Sum and Chi Square tests compared data between specific time points. Generalized estimating equations and linear contrasts of the parameter estimates compared data at the three time points. Results: The final analysis included 98 subjects (Intervention = 49, Control = 49). The composite score was not different between groups (I = 12.8 ± 4.5 points, C = 12.7 ± 4.9 points, p = 0.9405). Improvements were noted in understanding and motivation in the entire cohort, but these changes were not influenced by the intervention. Medication prescribing declined at 3 and 12 months after CABG without significant differences between the groups. Conclusions: Disease understanding, motivation to reduce risk, and medication use are robust at hospital discharge but the latter declines with time and was not improved by our intervention. These findings are concerning and warrant further study.

关键词： Secondary Prevention Coronary Artery Disease Coronary Artery Bypass

Reprogramming mouse ear mesenchymal stem cells (EMSC) expressing the Dlk1-Dio3 imprinted gene cluster

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Stem Cell Discovery 2013年第1期3卷 64-71页

作者： Ru Gao Jong S. Rim Karen l. Strickler Christian W. Barnes lettie l. Harkins Jaroslaw Staszkiewicz Jeffery M. Gimble Barbara Gawronska-Kozak gregory H. leno Kenneth J. Eilertsen Department of Anatomy & Cell Biology Carver College of Medicine University of Iowa Iowa City USA Institute of Animal Reproduction and Food Research of Polish Academy of Sciences Olsztyn Poland NuPotential Inc. Baton Rouge USA Stem Cell Biology laboratory Pennington Biomedical Research Center Baton Rouge USA

The identification of a single, early marker for full developmental potential of induced pluripotent stem (iPS) cells has proven elusive. Recently, however, activation of the imprinted gene cluster, Dlk1-Dio3 has emerged as a viable candidate in the mouse. To explore the relationship between Dlk1-Dio3 expression and developmental potential more fully, we used murine ear mesenchymal stem cells (mEMSC) for iPS cell induction. Mouse EMSC are easily obtained and share functional characteristics with embryonic stem (ES) cells and therefore, may be a reliable non-embryonic source for iPS cell production. We report that mEMSC express high levels of Gtl2, a maternally expressed gene within the Dlk1-Dio3 imprinted cluster. Moreover, mEMSC produce Gtl2 expressing (Gtl2on) iPSC clones that share functional characteristics with ES cell clones. The production of Gtl2on iPS cell clones from mEMSC provides a new model with which to investigate the regulation of Dlk1-Dio3 cluster activity during direct cell reprogramming.

关键词： iPSCs Reprogramming Pluripotent Stem Cell

用于中国人群的压力管理、心身增弹方案(SMART-C)及其子方案健康睡眠(HS)的编制

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世界睡眠医学杂志 2017年第2期4卷 72-75页

作者：王芳 Herbert Benson gregory l.Fricchione John W.Denninger 中国中医科学院广安门医院睡眠心理科北京100053 哈佛大学医学院麻省总医院本森亨利心身医学研究所波士顿02114

压力的定义有很多,与慢性压力相关的疾病谱系非常广泛。压力管理相关疗法与心身医学密切相关。压力反应和放松反应的发现,为心身疗法应用于压力管理提供了依据。哈佛大学医学院麻省总医院本森亨利心身医学研究所的赫伯特·本森教授团队... 详细信息

压力的定义有很多,与慢性压力相关的疾病谱系非常广泛。压力管理相关疗法与心身医学密切相关。压力反应和放松反应的发现,为心身疗法应用于压力管理提供了依据。哈佛大学医学院麻省总医院本森亨利心身医学研究所的赫伯特·本森教授团队一直致力于运用心身疗法来干预慢性压力的临床和科研工作。他们开发出压力管理、弹性训练方案(SMART),专门针对压力相关症状或疾病工作。笔者通过在哈佛大学医学院麻省总医院本森亨利心身医学研究所两年博士后的工作和学习,结合自身临床经验,在充分考虑中美两国文化背景差异的基础上,编制出适用于中国人群的压力管理、心身增弹方案(SMARTC)及以健康睡眠(HS)为代表的若干子方案。用于临床实践,取得了一定的疗效。

关键词：心身医学压力管理睡眠质量