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NKG7 mRNA therapy increases the anti-tumor cytotoxicity of CD8+ T cells and improves response to immune checkpoint inhibitors

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NKG7 mRNA therapy increases the anti-tumor cytotoxicity of C...

NKG7 mRNA therapy increases the anti-tumor cytotoxicity of CD8+ T cells and improves response to immune checkpoint inhibitors

2021年中国肿瘤标志物学术大会暨第十五届肿瘤标志物青年科学家论坛

作者： Ti Wen whitney barham Ying Li Henan Zhang Joanina K.Gicobi Jacob B.Hirdler Xin Liu Hyoungjun Ham Fabrice Lucien Daniel D.Billadeau Haidong Dong The First Hospital of China Medical University Mayo Clinic Mayo Clinic College of Medicine and Science

Translating information gained from single cell RNA-sequencing(scRNA-seq) analyses into clinical therapeutics remains a challenge. However, with the advent of technology that makes mRNA-based modulation of primary cells possible, targets identified in scRNA-seq datasets can now be manipulated directly. Here we model this approach in the context of cancer immunotherapy. We performed scRNA-seq analysis of peripheral CD8 T cells from patients who received anti-PD-1 checkpoint blockade and found that natural killer cell granule protein-7(NKG7) gene expression was decreased in non-responding patients. Functional assays revealed that reduced NKG7 levels compromised cytolytic granule localization and release. Furthermore, transfection of CD8 T cells with NKG7 mRNA promoted tumor cell killing both in vitro and in vivo. Thus, we identify NKG7 as critical for response to anti-PD-1 treatment, demonstrate the efficacy of NKG7 mRNA as a therapeutic strategy for improving cancer immunotherapy, and provide a model for translating scRNA-seq findings into mRNA-based therapy.

关键词： cancer immunotherapy anti-PD-1 treatment scRNA-seq NKG7

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NKG7 mRNA therapy increases the anti-tumor cytotoxicity of C...

An augmented and interactive exhibition of an archived model for Frederick Kiesler's Endless House, 1959

第十四届全国免疫学学术大会

作者： Ti Wen whitney barham Ying Li Henan Zhang Joanina K. Gicobi Jacob B. Hirdler Xin Liu Hyoungjun Ham Fabrice Lucien Hu Li Daniel D. Billadeau Haidong Dong Department of Medical Oncology the First Hospital of China Medical University Mayo Clinic Mayo Clinic College of Medicine and Science

Translating information gained from single cell RNA-sequencing(scRNA-seq) analyses into clinical therapeutics remains a challenge. However, with the advent of technology that makes mRNA-based modulation of primary cells possible, targets identified in scRNA-seq datasets can now be manipulated directly. Here we model this approach in the context of cancer immunotherapy. We performed scRNA-seq analysis of peripheral CD8+ T cells from patients who received anti-PD-1 checkpoint blockade and found that natural killer cell granule protein-7(NKG7) gene expression was decreased in non-responding patients. Functional assays revealed that reduced NKG7 levels compromised cytolytic granule localization and release. Furthermore, transfection of CD8+ T cells with NKG7 mRNA promoted tumor cell killing both in vitro and in vivo. Thus, we identify NKG7 as critical for response to anti-PD-1 treatment, demonstrate the efficacy of NKG7 mRNA as a therapeutic strategy for improving cancer immunotherapy, and provide a model for translating scRNA-seq findings into mRNA-based therapy.

关键词： Cancer Immunotherapy anti-PD-1 response NKG7 scRNA-seq

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Frontiers of Architectural Research 2022年第6期11卷 993-1006页

作者： Chantelle Niblock Laura McGuire John Harding Gerd Zillner Chris Hamill Andrew whitney School of Natural and Built Environment Queens University of BelfastNorthern IrelandBT71NNUK School of Architecture University of Hawaii at MānoaHonoluluHI96822USA School of Architecture University of ReadingReadingBerkshireRG66URUK Austrian Frederick and Lillian Kiesler Private Foundation Mariahilfer Straße1060WienAustria Hotknife Digital Media NottinghamNG13HDUK

This research explores the potential of an immersive and interactive online archive to enhance our understanding of historic architecture through the study of *** reports on implementing an augmented reality mobile application that exhibits a model for the unbuilt Endless House,1959,by Frederick Kiesler.A reflective critique,from the researcher’s point of view,and initial feedback from a small sample of architecture students,provides an insight into users’experience of the exhibition,its value as a research tool,and as an educational *** on existing technologies and established research methods,we present an alternative way of exhibiting a large-scaled model for public engagement and research collaboration between academics,archivists,and *** discuss the development of the mobile application with interactive features specifically designed for an architectural *** touches on issues associated with documenting,interpreting,and exhibiting architectural models,emphasizing accessibility,accuracy,engagement,combining 3D and 2D digital assets,and user *** was found that the interactive and immersive features of the exhibition enhanced the researchers’scope to spatially inspect the model,visually experience it,collaborate with others,and strengthen connections between the model and other examples of Kiesler’s textual and visual archival materials.

关键词： Augmented model Unbuilt architecture Frederick Kiesler Interactive exhibition Endless house

Cost Effective Trend in Epistaxis Management

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International Journal of Otolaryngology and Head & Neck Surgery 2023年第3期12卷 85-91页

作者： Roman Sereda whitney Hall Department of Physician Assistant Medicine University of Tampa Tampa Florida USA

Background: Epistaxis affects much of the population and is a common medical complaint seen across a variety of medical settings. Current standard of care treatment includes a range of options from topical therapy to invasive intranasal device insertion in the absence of on-demand specialist involvement. Aim: The aim of this article is to not only highlight superior outcomes in patients with acute nontraumatic epistaxis that are treated with noninvasive nebulized tranexamic acid instead of more invasive options, but also monetary benefit to the community through reduced costs. Case Presentation: this case report highlights a successful epistaxis resolution with use of tranexamic acid in a 64-year-old female after she was subjected to intranasal device insertion that did not resolve bleeding. Conclusion: Nebulized tranexamic acid is a cost-effective medication that not only reduces rates of recurrence, but it also increases patient satisfaction while minimizing overall healthcare costs, and therefore should be the first choice therapy in uncomplicated epistaxis management.

关键词： Epistaxis TXA Tranexamic Acid Rhinorocket Nasal Packing

Vestibular rehabilitation in cerebellar ataxia with neuropathy and vestibular areflexia syndrome(CANVAS)-A case report

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中华耳科学杂志:英文版 2023年第4期18卷 199-207页

作者： R.G.Harrell A.R.Cassidy B.N.Klatt P.Hovareshti S.L.whitney School of Health and Rehabilitation Sciences Department of Physical TherapyUniversity of PittsburghPittsburghPA15219USA Rehabilitation Institute University of Pittsburgh Medical CenterPittsburghPA15219USA BlueHalo Intelligent AutomationRockvilleMD20855USA Department of Otolaryngology University of Pittsburgh Medical SchoolPittsburghPA15219USA The University of Pittsburgh Department of Physical Therapy100 Technology Dr.Pittsburgh PA 15219

Background and purpose:Cerebellar ataxia,neuropathy,and vestibular areflexia syndrome(CANVAS)is a neurodegenerative disease of the *** disease progression is slow,with up to 25%of people diagnosed needing to use a wheelchair after 15 years from *** symptoms arise from centrally-mediated ocular movement degradation and the reduced vestibular-ocular reflex functioning *** date,no report has shown an improvement in VOR gain or gait outcome measures in someone with CANVAS after a course of vestibular physical *** description:A 65-year-old male,Patient X,first noticed symptoms in his fourth decade of life and was diagnosed with(CANVAS)in his seventh *** X reported numbness and tingling in his hands and feet,decreased ability to perform daily activities,and several ***:Patient X completed a four-month course of vestibular physical therapy,including vestibular ocular reflex exercises,balance training,gait training,and the VestAid application for eye gaze compliance *** Vestaid application uses eyes and facial recognition software to record the percentage of time that the patient kept their eyes on the ***:After vestibular therapy,Patient X had a clinically meaningful improvement in gait speed:from 1.02 m/s to 1.13 m/s and in the Functional Gait Assessment from 20/30 to 27/*** X's eye gaze compliance improved from a median of 43%(range 25e68%)to a median of 67%(58e83%).Discussion:This case study demonstrates that vestibular rehabilitation improved eye gaze compliance and functional outcomes in a person living with CANVAS.

关键词： vestibular neuropathy meaningful

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Exposure to air pollutants in Vietnam:Assessing potential risk for tourists

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Journal of Environmental Sciences 2018年第11期30卷 147-154页

作者： Pallavi Pant whitney Huynh Richard E.Peltier Department of Environmental Health Sciences School of Public Health and Health SciencesUniversity of Massachusetts

Tourism can form an important component of a nation＇s GDP, and Vietnam is among the most visited countries in Southeast Asia. Most studies on personal exposure focus on the general population, or occupational cohorts with exposure to specific pollutants. However, short-term exposure to air pollutants while visiting regions with high levels of air pollution can lead to acute health effects. A personal exposure study was conducted across three cities in Vietnam to estimate exposure to particulate matter （PM2.5） and black carbon for tourists. Measurements were conducted during the wet season in 2014 in Ho Chi Minh City, Da Lat and Nha Trang using portable instrumentation. Average 24-hr PM2.5 and BC exposures were estimated as 18.9 ± 9.24 and 3.41 ± 1.33 μg/m3 and among the three cities, Ho Chi Minh was found to have the highest PM2.5 concentrations. Environmental tobacco smoke, commuting and street food stands were found to contribute to highest levels of exposure to PM2.s and BC across all cities.

关键词： Vietnam PM2.5 BC Exposure ETS Commute

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猫和土拨鼠

中学生英语 2022年第27期 14-17页

作者： Mary Z.whitney 陈佳武汉市光谷五小

“我不想再在我们的院子里看到那只猫了。”丈夫一边说着,一边发出嘘声将那只漂亮的花斑猫赶过小溪,赶回到邻居的院子里。“祝你好运!猫不像狗,亲爱的。它们非常独立,喜欢随处游荡,尤其是当它们在捕鼠的时候。”

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Cool-season annual pastures with clovers to supplement wintering beef cows nursing calves

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Journal of Animal Science and Biotechnology 2012年第4期3卷 221-226页

作者： Stacey A Gunter whitney A Whitworth T Gregory Montgomery Paul A Beck United States Department of Agriculture Agricultural Research Service Southern Plains Range Research Station University of Arkansas at Monticello Division of Agriculture Southeast Research & Extension Center University of Arkansas Division of Agriculture Southwest Research & Extension Center University of Arkansas

In December of 3 years, 87 beef cows with nursing calves （.594 ± 9.8 kg; calving season, September to November） at side were stratified by body condition score, body weight, cow age, and calf gender and divided randomly into 6 groups assigned to 1 of 6 cool-season annual pastures （0.45 ha/cow） that had been interseeded into a dormant common bermudagrass （Cynodon dactylon [L.] Pers.）/bahiagrass （Paspalum notatum Flugge） sod. Pastures contained 1 of the following 3 seeding mixtures （2 pastures/mixture）： 1） wheat （Triticum aestivurn L.） and ryegrass （Lofium multiflorum Lain., WRG）, 2） wheat and ryegrass plus red clover （Trifolium pretense L, WRR）, or 3） wheat and ryegrass plus white （Trifofium repens L.） and crimson clovers （Trifolium incarnatum L., WRW）. All groups had ad libitum access to grass hay （12% crude protein; 58% total digestible nutrients）. The second week in December, cow estrous cycles were synchronized and artificially inseminated. In late December, a bull was placed with each group for 60-d. Data were analyzed with an analysis of variance using a mixed model containing treatment as the fixed effect and year as the random effect. Body weight and condition scores did not differ （P ≥ 0.27） among cows between February and June. Calf birth weights or average daily gain did not differ （P≥ 0.17） among treatments; however, calves grazing pastures with clovers did tend （P= 0.06） to weigh more than calves grazing grass only. Weaning weight per cow exposed to a bull was greater （P= 0.02） for WRR and WRW than WRG. Cows grazing winter-annual pastures containing clovers tended to wean more calf body weight per cow exposed to a bull than cows grazing the grass only pastures.

关键词： Annual ryegrass Beef cows Clovers Nitrogen Pasture 1

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Non-pharmacological therapies for inflammatory bowel disease: Recommendations for self-care and physician guidance

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World Journal of Gastroenterology 2018年第28期24卷 3055-3070页

作者： whitney Duff Natasha Haskey Gillian Potter Jane Alcorn Paulette Hunter Sharyle Fowler College of Kinesiology University of Saskatchewan Irving K Barber School of Arts and Science University of British Columbia-Okanagan Department of Psychology University of Saskatchewan College of Pharmacy and Nutrition University of Saskatchewan St Thomas More College University of Saskatchewan Department of Medicine University of Saskatchewan

We performed a scoping review on sought-after complementary therapies for patients with inflammatory bowel disease(IBD), specifically diet, physical activity and exercise(PA/E), and psychotherapy. We aim to update patients with IBD on therapies for self-care and provide physicians with guidance on how to direct their patients for the management of IBD. A search of MEDLINE, EMBASE, and PUBMED was completed in Sept 2016. Studies on diet, PA/E, or psychotherapy in patients with IBD were included. Medical Subject Heading terms and Boolean operators were used. The search was limited to full-text English articles describing an adult population. This review included 67 studies: Diet(n = 19); PA/E(n = 19); and psychotherapy(n = 29). We have made the following recommendations:(1) Diet: Consumption of diets rich in vegetables, fruit and soluble fiber may be beneficial in IBD. A trial of a low FODMAP diet can be considered in those patients with functional gastrointestinal symptoms. Restrictive diets are lacking in evidence and should be avoided;(2) PA/E: Regular lowmoderate intensity activity, including cardiovascular and resistance exercise, has been shown to improve quality of life(QOL) and may improve inflammation; and(3) psychotherapy: Therapies such as cognitive-behavioural interventions, mindfulness, hypnosis, and stress management have been shown to improve QOL, but evidence is limited on their impact on anxiety, depression, and disease activity. Overall, these complementary therapies are promising and should be used to treat patients with IBD from a more holistic perspective.

关键词： Scoping review Inflammatory bowel disease Diet Exercise Psychotherapy