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Response to osimertinib in a colorectal cancer patient with an EGFR T790M mutation: A case report

World Journal of Gastrointestinal Oncology 2023年第10期15卷 1829-1834页

作者： Blake Buzard Lindsey Douglass beth gustafson Jennifer Buckley Marc Roth Lara Kujtan Dhruv Bansal Cancer Institute St.Luke's HospitalKansasMO 64111United States Department of Medical Oncology University of Missouri-Kansas CityKansasMO 64108United States Department of Hematology/Oncology St.Luke's Cancer InstituteKansasMO 64111United States

BACKGROUND Although common in lung cancer,somatic epidermal growth factor receptor(EGFR)mutations are rarely found in colorectal cancer,occurring in approximately 3%of *** with anti-EGFR antibodies is commonplace,but EGFR tyrosine kinase inhibitors are not standard treatments in colorectal *** we report a case of sustained response to osimertinib in a colorectal cancer patient with an EGFR T790M mutation on cell-free DNA *** SUMMARY A 72-year old woman with a past medical history of post-polio syndrome confined to a wheelchair,scoliosis and hypothyroidism presented with metastatic sigmoid colon adenocarcinoma with hepatic *** generation sequencing revealed a RAS/RAF wild-type,microsatellite stable,PD-L1 negative *** in TP3 and APC were also identified,as well as EGFR ***-free DNA analysis revealed an EGFR T790M *** was unable to tolerate first-line treatment with panitumumab,5-fluorouracil and leucovorin,progressed on second-line treatment with trifluridine/tipiracil plus bevacizumab,and was unable to tolerate third-line treatment with *** was started on fourth-line treatment with off-label osimertinib,with clinical response–decrease in size of hepatic metastases and a pericardial *** remained on treatment with osimertinib for seven *** This case shows the benefit of multi-gene sequencing assays to identify potential therapeutic options in patients with refractory disease.

关键词： Colorectal cancer Osimertinib Epidermal growth factor receptor T790M Precision oncology Tyrosine kinase inhibitor Case report

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COVID-19 vaccination produces exercise-responsive SARS-CoV-2 specific T-cells regardless of infection history

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Journal of Sport and Health Science 2024年第1期13卷 99-107页

作者： Kyle A.Smith Tiffany M.Zúñiga Forrest L.Baker Helena Batatinha Charles R.Pedlar Shane C.Burgess Michael P.gustafson Emmanuel Katsanis Richard J.Simpson School of Nutritional Sciences and Wellness The University of ArizonaTucsonAZ 85721USA Department of Pediatrics The University of ArizonaTucsonAZ 85724USA Faculty of Sport Allied Health and Performance ScienceSt.Mary's UniversityTwickenham TW14SXUK Institute of Sport Exercise and Health University College LondonLondon WC1E 7HUUK Department of Animal and Comparative Biomedical Sciences The University of ArizonaTucsonAZ 85721USA The University of Arizona Cancer Center The University of ArizonaTucsonAZ 85719USA Laboratory Medicine and Pathology Mayo Clinic ArizonaPhoenixAZ 85054USA Department of Immunobiology The University of ArizonaTucsonAZ 85724USA Department of Medicine The University of ArizonaTucsonAZ 85724USA Department of Pathology The University of ArizonaTucsonAZ 85724USA

Background:The mobilization and redistribution of severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)specific T-cells and neutralizing antibodies(nAbs)during exercise is purported to increase immune surveillance and protect against severe coronavirus disease 2019(COVID-19).We sought to determine if COVID-19 vaccination would elicit exercise-responsive SARS-CoV-2 T-cells and transiently alter nAb ***:Eighteen healthy participants completed a 20-min bout of graded cycling exercise before and/or after receiving a COVID-19 *** major leukocyte subtypes were enumerated before,during,and after exercise by flow cytometry,and immune responses to SARS-CoV-2 were determined using whole blood peptide stimulation assays,T-cell receptor(TCR)-βsequencing,and SARS-CoV-2 nAb ***:COVID-19 vaccination had no effect on the mobilization or egress of major leukocyte subsets in response to intensity-controlled graded ***,non-infected participants had a significantly reduced mobilization of CD4+and CD8+naive T-cells,as well as CD4+central memory T-cells,after vaccination(synthetic immunity group);this was not seen after vaccination in those with prior SARS-CoV-2 infection(hybrid immunity group).Acute exercise after vaccination robustly mobilized SARS-CoV-2 specific T-cells to blood in an intensity-dependent *** groups mobilized T-cells that reacted to spike protein;however,only the hybrid immunity group mobilized T-cells that reacted to membrane and nucleocapsid *** increased significantly during exercise only in the hybrid immunity ***:These data indicate that acute exercise mobilizes SARS-CoV-2 specific T-cells that recognize spike protein and increases the redistribution of nAbs in individuals with hybrid immunity.

关键词： Anti-viral COVID-19 Exercise immunology SARS-CoV-2 T-Cells Vaccine

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Quantifying Kinematic Tremor in an NGLY1-Deficient Individual: A Case Study

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Case Reports in Clinical Medicine 2024年第1期13卷 25-36页

作者： Brock Futrell Christopher Alexander Malaya Dacia Martinez Diaz Christian Alfaro Hannah Elizabeth gustafson Subhalakshmi Chandrasekaran Rhea Mohan Phatak Bernhard Suter Charles Shannon Layne Department of Health and Human Performance University of Houston Houston USA Center for Neuromotor and Biomechanics Research University of Houston Houston USA Department of Computer Science and Engineering Texas A&M University College Station USA Blue Bird Circle Rett Center Texas Children’s Hospital Houston USA Baylor College of Medicine Houston USA Center for NeuroEngineering and Cognitive Science University of Houston Houston USA

NGLY1 Deficiency is an autosomal recessive congenital disorder that has been identified in less than 100 individuals. Most individuals with NGLY1 Deficiency display hyperkinetic movement disorders, including choreiform, athetoid, dystonic myoclonic, dyskinetic, and dysmetric movements. Developing a consistent and concise consensus on the classification and evaluation of tremors is essential to forward the research and treatment of tremors. It has also been reported that some individuals with NGLY1 Deficiency demonstrate tremor, but such tremor has never been formally investigated. The primary objective of this study is to determine if an individual with NGLY1 Deficiency demonstrates an identifiable tremor during a series of arm movements and, if so, describe the frequency and power characteristics of that tremor. Arm movement kinematics were obtained using a 16-camera Vicon system, and time series trajectory waveforms for three planes of a marker placed on the hand were developed. Custom MATLAB scripts were utilized to compute Fast Fourier Transformations of the data within the identified waveform segments. A mean frequency of 2.30 Hz (SD = 1.05) with a mean power of 5.02 |P1(f)| (SD = 4.63) suggests that our participant’s kinematic data did display a persistent tremor in both hands across all tasks and movement planes. Analyses of the reaching hand and the non-reaching hand suggest the participant displayed an action tremor in both postural and intention (kinetic) tremors. Future directions should include assessing additional individuals with NGLY1 Deficiency to determine if the tremor is a distinguishable disorder behavior. Additionally, evaluating other anatomical sites, such as the elbow, head, and lower limbs, would provide further insights into the characteristics of this tremor.

关键词： Tremor NGLY Fast Fourier Transformation Reaching Hyperkinetic Movement

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3-Dimensional Kinematic Comparison of Arm Movements between an Individual with NGLY1 Deficiency and a Neurotypical Individual

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Case Reports in Clinical Medicine 2024年第4期13卷 122-146页

作者： Charles S. Layne Christopher A. Malaya Brock Futrell Dacia Martinez Diaz Christian Alfaro Hannah E. gustafson Subhalakshmi Chandrasekaran Rhea M. Phatak Bernhard Suter Department of Health and Human Performance University of Houston Houston TX USA Center for Neuromotor and Biomechanics Research University of Houston Houston TX USA Center for Neuro Engineering and Cognitive Science University of Houston Houston TX USA Department of Computer Science and Engineering Texas A&M University College Station TX USA Blue Bird Circle Rett Center Texas Children&#8217s Hospital Houston TX USA Baylor College of Medicine Houston TX USA

NGLY1 Deficiency is an ultra-rare autosomal recessively inherited disorder. Characteristic symptoms include among others, developmental delays, movement disorders, liver function abnormalities, seizures, and problems with tear formation. Movements are hyperkinetic and may include dysmetric, choreo-athetoid, myoclonic and dystonic movement elements. To date, there have been no quantitative reports describing arm movements of individuals with NGLY1 Deficiency. This report provides quantitative information about a series of arm movements performed by an individual with NGLY1 Deficiency and an aged-matched neurotypical participant. Three categories of arm movements were tested: 1) open ended reaches without specific end point targets;2) goal-directed reaches that included grasping an object;3) picking up small objects from a table placed in front of the participants. Arm movement kinematics were obtained with a camera-based motion analysis system and “initiation” and “maintenance” phases were identified for each movement. The combination of the two phases was labeled as a “complete” movement. Three-dimensional analysis techniques were used to quantify the movements and included hand trajectory pathlength, joint motion area, as well as hand trajectory and joint jerk cost. These techniques were required to fully characterize the movements because the NGLY1 individual was unable to perform movements only in the primary plane of progression instead producing motion across all three planes of movement. The individual with NGLY1 Deficiency was unable to pick up objects from a table or effectively complete movements requiring crossing the midline. The successfully completed movements were analyzed using the above techniques and the results of the two participants were compared statistically. Almost all comparisons revealed significant differences between the two participants, with a notable exception of the 3D initiation area as a percentage of the complete movement. The stati

关键词： NGLY1 Deficiency Developmental Disorders Kinematics 3 Dimensional Analyses

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Mental health-related healthcare service utilisation and psychotropic drug dispensation trends in British Columbia during COVID-19 pandemic:a population-based study

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General Psychiatry 2023年第1期36卷 50-57页

作者： Moe Zandy Sylvia El Kurdi Hasina Samji Geoff McKee Reka gustafson Kate Smolina BC Centre for Disease Control VancouverBritish ColumbiaCanada Faculty of Health Sciences Simon Fraser UniversityBurnabyBritish ColumbiaCanada School of Population and Public Health The University of British ColumbiaVancouverBritish ColumbiaCanada BC Children's Hospital Research Institute VancouverBritish ColumbiaCanada

Background The impact of the COVID-19 pandemic on the population’s mental health is vital for informing public health policy and ***,information on mental health-related healthcare service utilisation trends beyond the first year of the pandemic is *** We examined mental health-related healthcare service utilisation patterns and psychotropic drug dispensations in British Columbia,Canada,during the COVID-19 pandemic compared with the prepandemic *** We conducted a retrospective population-based secondary analysis using administrative health data to capture outpatient physician visits,emergency department visits,hospital admissions and psychotropic drug *** examined time trends of mental health-related healthcare service utilisation and psychotropic drug dispensations between January to December 2019(prepandemic period)and January 2020 to December 2021(pandemic period).In addition,we calculated age-standardised rates and rate ratios to compare mental health-related healthcare service utilisation before and during the first two years of the COVID-19 pandemic,stratified by year,sex,age and *** By late 2020,except for emergency department visits,utilisation of healthcare services recovered to prepandemic *** 2019 and 2021,the monthly average rate for overall mental health-related outpatient physician visits,emergency department visits and psychotropic drug dispensations increased significantly by 24%,5%and 8%,*** and statistically significant increases were observed among 10–14 year-olds(44%in outpatient physician visits,30%in emergency department visits,55%in hospital admissions and 35%in psychotropic drug dispensations)and 15–19 year-olds(45%in outpatient physician visits,14%in emergency department visits,18%in hospital admissions and 34%in psychotropic drug dispensations).Additionally,these increases were more prominent among females than males,with some variation for specif

关键词： service consequences Canada

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Introduction:innovative heritage-based post-crisis urban recovery strategies

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Built Heritage 2023年第2期7卷 1-2页

作者： Christer Gustafsson Matthias Ripp Department of Art History Uppsala University(SE)UppsalaSweden Department for cultural heritage RegensburgGermany

Resilience is a concept that has become more and more common during the last *** used in physics and psychology,just recently it has been transferred to the feld of urban planning,urban development and cultural *** purpose of this Special Issue of the international journal Built Heritage is to examine,and discuss,how the concept of resilience can be related to cultural *** understand resilience here in the sense of the SHELTER Resilience defnition which defnes diferent phases before,during and after a disaster or crisis.

关键词： journal disaster heritage

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EEG/ERP evidence of possible hyperexcitability in older adults with elevated beta-amyloid

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Translational Neurodegeneration 2022年第1期11卷 835-844页

作者： Hannes Devos Kathleen gustafson Ke Liao Pedram Ahmadnezhad Bradley Estes Laura E.Martin Jonathan D.Mahnken William M.Brooks Jeffrey M.Burns Department of Physical Therapy Rehabilitation Scienceand Athletic TrainingUniversity of Kansas Medical CenterKansas CityKS 66160USA Department of Neurology University of Kansas Medical CenterKansas CityKS 66160USA Hoglund Biomedical Imaging Center University of Kansas Medical CenterKansas CityKS 66160USA Department of Population Health University of Kansas Medical CenterKansas CityKS 66160USA Department of Biostatistics and Data Science University of Kansas Medical CenterKansas CityKS 66160USA University of Kansas Alzheimer’s Disease Center University of Kansas Medical CenterKansas CityKS 66160USA.

Background: Although growing evidence links beta-amyloid (Aβ) and neuronal hyperexcitability in preclinical mouse models of Alzheimer’s disease (AD), a similar association in humans is yet to be established. The first aim of the study was to determine the association between elevated Aβ (Aβ+) and cognitive processes measured by the P3 event-related potential (ERP) in cognitively normal (CN) older adults. The second aim was to compare the event- related power between CNAβ+ and CNAβ−. Methods: Seventeen CNAβ+ participants (age: 73 ± 5, 11 females, Montreal Cognitive Assessment [MoCA] score 26 ± 2) and 17 CNAβ- participants group-matched for age, sex, and MOCA completed a working memory task (n-back with n = 0, 1, 2) test while wearing a 256-channel electro-encephalography net. P3 peak amplitude and latency of the target, nontarget and task difference effect (nontarget−target), and event-related power in the delta, theta, alpha, and beta bands, extracted from Fz, Cz, and Pz, were compared between groups using linear mixed models. P3 ampli-tude of the task difference effect at Fz and event-related power in the delta band were considered main outcomes. Correlations of mean Aβ standard uptake value ratios (SUVR) using positron emission tomography with P3 amplitude and latency of the task difference effect were analyzed using Pearson Correlation Coefficient r. Results: The P3 peak amplitude of the task difference effect at Fz was lower in the CNAβ+ group (P = 0.048). Simi-larly, power was lower in the delta band for nontargets at Fz in the CNAβ+ participants (P = 0.04). The CNAβ+ partici-pants also demonstrated higher theta and alpha power in channels at Cz and Pz, but no changes in P3 ERP. Strong correlations were found between the mean Aβ SUVR and the latency of the 1-back (r = − 0.69;P = 0.003) and 2-back (r = − 0.69;P = 0.004) of the task difference effect at channel Fz in the CNAβ+ group. Conclusions: Our data suggest that the elevated amyloid in cognitively normal ol

关键词： Event-related potentials Electro-encephalography Working memory Older adults Preclinical Beta-amyloid

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Plaque herniation after stenting the culprit lesion with myocardial bridging in ST elevation myocardial infarction: A case report

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World Journal of Cardiology 2020年第2期12卷 91-96页

作者： Jeffrey Ma Gregory M gustafson Xuming Dai Division of Cardiology Theresa and Eugene M.Lang Center for Research and Education New York Presbyterian–Queens Hospital

BACKGROUND Myocardial bridging(MB)is increasingly recognized to stimulate atherogenesis,which may contribute to an acute coronary *** the coronary segment with MB has been recognized to have an increased risk of in-stent restenosis,stent fracture and coronary *** safety and efficacy of stenting the culprit lesion with overlaying MB in ST elevation myocardial infarction(STEMI)as primary reperfusion therapy has not been *** SUMMARY We reported a patient who presented with inferior STEMI with a culprit lesion of an acute thrombotic occlusion in the right coronary artery and thrombolysis and thrombin inhibition in myocardial infarction 0 *** the stent placement during primary percutaneous coronary intervention,intravascular ultrasound revealed MB overlying the stented segment where heavy atherosclerotic plaque were *** due to the combination of plaque herniation or prolapse caused by MB,as well as local increased inflammation and thrombogenicity,acute stent thrombosis occurred at this region,which led to acute stent *** patient required an emergent repeated cardiac catheterization and placing a second layer of stent to enhance the radial strength and reduce the inter-strut *** Plaque herniation or prolapse after stenting a MB segment in STEMI is a potential etiology for acute stent failure.

关键词： Case report ST elevation myocardial infarction Myocardial bridging Plaque herniation Plaque prolapse Intravascular ultrasound Acute stent thrombosis

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Remodeled structure and reduced contractile responsiveness of ocular ciliary artery in spontaneously hypertensive rats

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International Journal of Ophthalmology(English edition) 2019年第3期12卷 363-368页

作者： Ya-Ru Dong Claire E gustafson Jun Wang Ji-Zhe Cui Takeshi Yoshitomi Department of Ophthalmology the Second Hospital of Jilin University Department of Ophthalmology Akita University School of Medicine Division of Immunology and Rheumatology Department of Medicine Stanford University

AIM: To investigate the alterations in both structure and contractile responsiveness of ocular ciliary artery(OCA) in spontaneously hypertensive rat(SHR).METHODS: In this experiment, 20-week-old male SHR and Wistar Kyoto rat(WKY) were studied. The heart rate(HR), the blood pressure(BP; the systolic BP and the diastolic BP) of rats with an electronic sphygmomanometer were measured. Vascular morphometry and isometric tension measurement were used to investigate the alterations in structure and contractility of ***: A general narrowing of OCAs was observed in SHR compared to the control WYK. In SHR, the media of OCAs were thicker, the luminal diameters were smaller, and the media-to-lumen ratios were higher when compared with WKY(P0.05). Indomethacin(10 μmol/L) decreased the contractions induced by norepinephrine in OCAs from WKY(P0.05).CONCLUSION: Our results demonstrate that the structure and function of OCAs are altered in hypertension. OCAs from SHR are remodeled with decreased lumen diameter and increased media-to-lumen ratio. Moreover, the contractile responsiveness of OCAs from SHR is diminished due to the disruption of vasoconstrictive effect of prostaglandins.

关键词： remodeled structure contractile responsiveness ocular ciliary artery hypertension spontaneously hypertensive rat

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Extrapolating plot-scale CO_(2) and ozone enrichment experimental results to novel conditions and scales using mechanistic modeling

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Ecological Processes 2018年第1期7卷 348-367页

作者： Eric J.gustafson Mark E.Kubiske Brian R.Miranda Yasutomo Hoshika Elena Paoletti Institute for Applied Ecosystem Studies Northern Research StationUSDA Forest Service5985 Highway KRhinelanderWIUSA Institute of Sustainable Plant Protection National Council of ResearchVia Madonna del Piano 1050019 Sesto FiorentinoItaly

Introduction:The Aspen-FACE experiment was an 11-year study of the effect of elevated CO_(2) and ozone(alone and in combination)on the growth of model aspen communities(pure aspen,aspen-birch,and aspen-maple)in the field in northern Wisconsin,*** remains about how these short-term plotlevel responses might play out over broader temporal and spatial scales where climate change,competition,succession,and disturbances interact with tree-level *** this study,we used a new physiologybased approach(PnET-Succession v3.1)within the forest landscape model LANDIS-II to extrapolate the FACE results to broader temporal scales(and ultimately to landscape scale)by mechanistically accounting for the globally changing drivers of temperature,precipitation,CO_(2),and *** added novel algorithms to the model to mechanistically simulate the effects of ozone on photosynthesis through ozone-induced impairment of stomatal control(i.e.,stomatal sluggishness)and damage of photosynthetic capacity at the chloroplast ***:We calibrated the model to empirical observations of competitive interactions on the elevated CO_(2) and O_(3) plots of the Aspen-FACE experiment and successfully validated it on the combined factor *** used the validated model to extend the Aspen-FACE experiment for 80 *** only aspen clones competed,we found that clone 271 always dominated,although the ozone-tolerant clone was co-dominant when ozone was *** all treatments,when aspen clone 216 and birch competed,birch was always dominant or co-dominant,and when clone 216 and maple competed,clone 216 was dominant,although maple was able to grow steadily because of its shade *** also predicted long-term competitive outcomes for novel assemblages of taxa under each treatment and discovered that future composition and dominant taxa depend on treatment,and that short-term trends do not always persist in the long ***:We identified the strengths and weakne

关键词： Scaling Global change Elevated CO_(2) Ozone pollution Aspen-FACE Forest composition Carbon dynamics Forest landscape modeling LANDIS-II PnET-succession

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