tbuckley/cabot-search huggingface dataset:
Abstract 122: Hypoxia-enhanced proliferation and effector function of NK cells
Authors: Yunwon Moon, Seon Ah Lim, Kyung-Mi Lee, Hyunsung Park
Journal: Cancer Research (2018)

Abstract Hypoxia promotes tumor cell survival while providing immune cell shaping and resistance. Although NK cells function within hypoxic lymphatics and inflamed tissues, they were shown to mount impaired anti-tumor effector functions in ex-vivo hypoxic environment. This raises a question that additional cues exist in vivo to allow full NK cell activation. By varying the percentage and time of pO2 exposure ex-vivo, we were able to fine-tune a condition that reverses hypoxia-induced NK cell suppression to become highly proliferative and enhanced cytolytic phenotypes. We found that exposing NK cells to moderate hypoxia in the presence of IL-2 and feeder cells allowed HIF-1α stabilization and its target gene expression, metabolic changes toward glycolysis, specific upregulation of NKp44 receptor, and increased STAT3 phosphorylation with concomitant reduction of apoptosis and p16 senescence pathways. Therefore, the hypoxic exposure allows HIF-1α-mediated adaptation of mature NK cells toward highly proliferative and cytolytic NK phenotypes, which may occur in vivo at the time of tumor growth and inflammation. [This work was supported by the National Research Foundation of Korea (NRF), grants NRF-2013M3A9D3046248] Citation Format: Yunwon Moon, Seon Ah Lim, Kyung-Mi Lee, Hyunsung Park. Hypoxia-enhanced proliferation and effector function of NK cells [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 122.
Abstract 12767: Trajectory of Exercise Capacity in Childhood and Its Impact on Their Adult Pathophysiology in Patients After the Fontan Operation
Authors: Hideo Ohuchi, Jun Negishi, Yosuke Hayama, Kanae Noritake, Aya Miyazaki, Isao Shiraishi
Journal: Circulation (2016)

Background: Preserved exercise capacity in childhood may predict better long-term outcome in patients after the Fontan operation. Purpose: This study was to elucidate an impact of trajectory of exercise capacity in childhood on the long-term exercise capacity and non-cardiac multi-organ function. Method and Results: Since 1990, consecutive 197 Fontan patients had undergone two serial cardiopulmonary exercise testing (CPX) at the age of 8±2 and 14±2 years and we measured the change in %-predicted peak oxygen uptake (dPVO 2 : %). Of these, 94 patients had performed CPX in the adulthood (24±4 years). Our patients were subdivided into 2 groups; those with positive dPVO 2 (n=113, group I) and those with negative dPVO 2 (n=84, group D). Early era at operation, heterotaxy, protein losing enteropathy, high PVO 2 and plasma brain natriuretic peptide levels (BNP) at 1 st CPX had independent negative impact on dPVO 2 (p&lt;0.05-0.0001). Group I showed significantly higher PVO 2 and lower BNP in their adulthood, while 49 clinical events, including 9 deaths occurred after 2 nd CPX. When compared with group I, group D had high hazard ratio of 2.1 and 6.5 for morbidity and mortality, respectively (p&lt;0.05 for both); however, there were no differences in high prevalence of impaired glucose tolerance, liver MELD XI score, or 24-hour creatinine clearance between two groups in their adulthood. Conclusions: The trajectory of exercise capacity in childhood is improving in current Fontan children which is associated with better prognosis, higher PVO 2 and lower BNP in the adulthood. However, the non-cardiac multi-organ dysfunction may progress regardless of the trajectory.
Dynamics of Genome Alterations in Crohn's Disease–Associated Colorectal Carcinogenesis
Authors: Daniela Hirsch, Darawalee Wangsa, Yuelin J. Zhu, Yue Hu, Daniel C. Edelman, Paul S. Meltzer, Kerstin Heselmeyer-Haddad, Claudia Ott, Peter Kienle, Christian Galata, Karoline Horisberger, Thomas Ried, Timo Gaiser
Journal: Clinical Cancer Research (2018)

Purpose: Patients with inflammatory bowel diseases, that is, ulcerative colitis and Crohn's disease (CD), face an increased risk of developing colorectal cancer (CRC). Evidence, mainly from ulcerative colitis, suggests that TP53 mutations represent an initial step in the progression from inflamed colonic epithelium to CRC. However, the pathways involved in the evolution of CRC in patients with CD are poorly characterized.Experimental Design: Here, we analyzed 73 tissue samples from 28 patients with CD-CRC, including precursor lesions, by targeted next-generation sequencing of 563 cancer-related genes and array-based comparative genomic hybridization. The results were compared with 24 sporadic CRCs with similar histomorphology (i.e., mucinous adenocarcinomas), and to The Cancer Genome Atlas data (TCGA).Results: CD-CRCs showed somatic copy-number alterations (SCNAs) similar to sporadic CRCs with one notable exception: the gain of 5p was significantly more prevalent in CD-CRCs. CD-CRCs had a distinct mutation signature: TP53 (76% in CD-CRCs vs. 33% in sporadic mucinous CRCs), KRAS (24% vs. 50%), APC (17% vs. 75%), and SMAD3 (3% vs. 29%). TP53 mutations and SCNAs were early and frequent events in CD progression, while APC, KRAS, and SMAD2/4 mutations occurred later. In four patients with CD-CRC, at least one mutation and/or SCNAs were already present in non-dysplastic colonic mucosa, indicating occult tumor evolution.Conclusions: Molecular profiling of CD-CRCs and precursor lesions revealed an inflammation-associated landscape of genome alterations: 5p gains and TP53 mutations occurred early in tumor development. Detection of these aberrations in precursor lesions may help predicting disease progression and distinguishes CD-associated from sporadic colorectal neoplasia. Clin Cancer Res; 24(20); 4997-5011. ©2018 AACR.
Assessing the Competence of Aging Physicians Who Are Young at Heart
Authors: Warren R. Heymann
Journal: JAMA Dermatology (2018)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA Dermatology HomeNew OnlineCurrent IssueFor Authors Podcast Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA Dermatology journal
Association of Future Orientation With Violence Perpetration Among Male Youths in Low-Resource Neighborhoods
Authors: Alison J. Culyba, Kaleab Z. Abebe, Steven M. Albert, Kelley A. Jones, Taylor Paglisotti, Marc A. Zimmerman, Elizabeth Miller
Journal: JAMA Pediatrics (2018)

Association of Future Orientation With Violence Perpetration Among Male Youths in Low-Resource NeighborhoodsYouth violence is pervasive and increases risk of injury and incarceration. 1 Future orientation, defined as hopes and plans for the future, is associated with multiple prosocial outcomes, including school engagement and successful transition to adulthood. 2Research on the potentially protective role of future orientation in preventing violence perpetration is limited, and it has tended to focus narrowly on perceived life expectancy and, to a lesser extent, job aspirations. 3,4 With use of a more comprehensive measure, we examined the association between future orientation and violence perpetration, including fighting and weapon-related violence, among male youths in low-resource neighborhoods.Methods | Participants.We enrolled 866 males aged 13 to 19 years through youth-serving community agencies in 20 lowresource neighborhoods in Pittsburgh, Pennsylvania, from August 2015 to June 2017, in an ongoing cluster-randomized violence prevention trial.Eligible youths were residents in intervention site neighborhoods who were willing to participate in the prevention program.Participants completed baseline in-person surveys on tablets (iPad Air; Apple) about future orientation, violence perpetration, school enrollment, and demographic characteristics.Study personnel obtained verbal participant assent (for participants 13 to 17 years of age) or consent (for participants ≥18 years of age).Data were deidentified with a secret code that was used to link survey responses to study participants.This involved answering a series of survey questions that were then combined to generate the code.
Abstract 10641: Rheb-mTOR Signaling Pathway Regulates Protein Synthesis but Not Degradation in Post Neonatal Cardiomyocyte Growth
Authors: Takahito Tamai, Shungo Hikoso, Tomokazu Murakawa, Jota Oyabu, Takafumi Oka, Manabu Taneike, Toshihiro Takeda, Osamu Yamaguchi, Hiroyuki Nakayama, Kazuhiko Nishida, Issei Komuro, Kinya Otsu
Journal: Circulation (2011)

Rheb (Ras homologue enriched in brain) is a major activator of mTOR. Rheb-mTOR pathway is a critical mechanism for maintenance of homeostasis, cell growth and stress response by regulating both protein synthesis and degradation. In this study, we attempted to clarify the role of Rheb-mTOR pathway in the heart using cardiac-specific Rheb-deficient mice (Rheb-/-). We generated floxed Rheb mice and crossed them with transgenic mice expressing Cre recombinase in cardiac-specific mannner to generate Rheb-/-. Rheb-/- were born in Mendelian ratio, but they started to die 8 days after birth and all of them had died until 10 days after birth. Echocardiographic analysis revealed that chamber dimension and contractile function of Rheb-/- were indistinguishable from those of control mice (Rheb+/+) 5 days after birth. However, Rheb-/- exhibited cardiac dilatation and reduced contractility 8 days after birth (LV end diastolic dimension, Rheb-/-: 2.5 ± 0.2 mm vs. Rheb+/+: 2.1 ± 0.2 mm, p
Abstract 120: HIF1 Alpha Can be Inhibited in the Heart by Protein Kinase C Binding Protein 1
Authors: Kathryn J Schunke, Karen H Chang, Chad B Walton, Ralph V Shohet
Journal: Circulation Research (2016)

Hypoxia-inducible factor 1 alpha (HIF-1α) is a key transcription factor responsible for the induction of genes that facilitate adaptation to hypoxia. The HIF-1 heterodimer (HIF-1α and HIF-1ß) recognizes a consensus element designated the hypoxia response element (HRE) within the enhancer regions of target genes that are implicated in many different cellular functions that ameliorate hypoxic stress. To study HIF-1 signaling in the heart, our lab developed a mouse model in which an oxygen-stable form of HIF-1α can be inducibly expressed in cardiac myocytes with a tet-off system . Remarkably, expression of the transgene generated two distinct phenotypes. One was the expected expression of HIF-regulated transcripts and associated HIF–related changes in cardiac angiogenesis and contractility. The other was a “resistant phenotype” with much less expression of typical HIF-response genes and substantial expression of a zinc-finger protein, a receptor for protein kinase C called PRKCBP1, also known as ZMYND8. We have demonstrated that this second phenotype is due to an insertion of a fragment of DNA upstream of the PRKCBP1 gene that contains two additional HREs and leads to substantial HIF binding, assessed by ChIP, and transcriptional activation. This inserted allele is found only in the FVB strain of mice that contributed the αMHC-tet binding protein allele to the transgenic strain. In HEK293 cells transfected with oxygen-stable HIF1α and PRKCBP1 we demonstrated inhibition of HIF-1 activity by a luciferase reporter assay. In the MCF-7 breast cancer cell line we have shown that increased expression of PRKCBP1 produces inhibition of HIF degradation in normoxia. This and co-immunoprecipitation of HIF with PRKCBP1 suggests a direct interaction of the two proteins that acts to inhibit HIF action. We have genetic, transcriptional, biochemical, and physiological evidence that PRKCBP1 inhibits HIF activity through direct interaction in a homeostatic mechanism mediated by transcriptional control.
Impact of Graphene on the Efficacy of Neuron Culture Substrates
Authors: Rachel A. Fischer, Yuchen Zhang, Michael L. Risner, Deyu Li, Yaqiong Xu, Rebecca M. Sappington
Journal: Advanced Healthcare Materials (2018)

Abstract How graphene influences the behavior of living cells or tissues remains a critical issue for its application in biomedical studies, despite the general acceptance that graphene is biocompatible. While direct contact between cells and graphene is not a requirement for all biomedical applications, it is often mandatory for biosensing. Therefore, it is important to clarify whether graphene impedes the ability of cells to interact with biological elements in their environment. Here, a systematic study is reported to determine whether applying graphene on top of matrix substrates masks interactions between these substrates and retinal ganglion cells (RGCs). Six different platforms are tested for primary RGC cultures with three platforms comprised of matrix substrates compatible with these neurons, and another three having a layer of graphene placed on top of the matrix substrates. The results demonstrate that graphene does not impede interactions between RGCs and underlying substrate matrix, such that their positive or negative effects on neuron viability and vitality are retained. However, direct contact between RGCs and graphene reduces the number, but increases basal activity, of functional cation channels. The data indicate that, when proper baselines are established, graphene is a promising biosensing material for in vitro applications in neuroscience.
Abstract 16899: Change in Cardiorespiratory Fitness is Inversely Related to Mortality Among Black and White Patients: Data From the Henry Ford Exercise Testing (FIT) Project
Authors: Jonathan K Ehrman, Clinton A Brawner, Mouaz H Al-Mallah, Waqas T Qureshi, John R Schairer, Michael J Blaha, Steven J Keteyian
Journal: Circulation (2015)

Background: Cardiorespiratory fitness (CRF) is inversely related to all-cause mortality and cardiovascular-related morbidity and mortality. However, there is limited data describing whether change in CRF is associated with improved outcomes. Hypothesis: Change in CRF between two clinical exercise stress tests is related to risk of all-cause mortality. Methods: In this retrospective, observational study, we identified 14,305 patients (age = 55 ± 11 y; 39% women; 30% non-white) who completed two clinically-indicated exercise tests that were at least 12 mo apart between 1991 and 2009 within the Henry Ford Health System. CRF was quantified in metabolic equivalents of task (METs) estimated from peak treadmill speed and grade. All-cause mortality was identified through April 2013 using the Social Security Death Index. Cox regression analysis was used to evaluate the risk of mortality associated with change in CRF between tests 1 and 2. Change in CRF was analyzed as the change in categorization between Poor Fitness (&lt;7 METs) and Fit (≥ 7 METs) and as an absolute change in peak METs. Based on data at test 1, covariates included age; sex; race; cardiovascular risk factors; medications; and history of coronary artery disease, heart failure, and atrial fibrillation; as well as year of test 1 and years between tests 1 and 2. Results: The mean time between test 1 and 2 was 4.3 ± 2.8 y. During 9.4 ± 3.9 y of follow-up after test 2, there were 1,980 (14%) deaths. Adjusted Cox regression results are shown in the Table. Among all patients, each 1 MET increase in CRF at test 2 was associated with a 5% lower risk of mortality (hazard ratio 95% confidence interval 0.94, 0.97; p &lt; 0.001). Conclusions: Among men and women referred for a clinical exercise test, change in CRF from Poor Fitness to Fit is associated with a 38% lower risk of all-cause mortality relative to patients who remain Unfit. These data support the importance of improving CRF and the clinical utility of serial assessments of CRF in risk assessment.
Abstract 16449: Uric Acid Levels Predict Coronary Artery Disease but Not Stroke in Essential Hypertension: Data From a Greek 8-Year-Follow-Up Study
Authors: Costas Tsioufis, Kyriakos Dimitriadis, Athanasios Kordalis, Costas Thomopoulos, Lefki Nikolopoulou, Eirini Andrikou, Thodoris Kalos, Dimitrios Tousoulis
Journal: Circulation (2016)

Introduction: The exact role of uric acid in cardiovascular risk prediction remains to be further determined. Hypothesis: The aim of the present study was to assess the predictive role of uric acid...
Copy number profiling across glioblastoma populations has implications for clinical trial design
Authors: Patrick J Cimino, Lisa McFerrin, Hans-Georg Wirsching, Sonali Arora, Hamid Bolouri, Raul Rabadan, Michael Weller, Eric C Holland
Journal: Neuro-Oncology (2018)

Copy number alterations form prognostic molecular subtypes of glioblastoma with clear differences in median overall survival. In this study, we leverage molecular data from several glioblastoma cohorts to define the distribution of copy number subtypes across random cohorts as well as cohorts with selection biases for patients with inherently better outcome. Copy number subtype frequency was established for 4 glioblastoma patient cohorts. Two randomly selected cohorts include The Cancer Genome Atlas (TCGA) and the German Glioma Network (GGN). Two more selective cohorts include the phase II trial ARTE in elderly patients with newly diagnosed glioblastoma and a multi-institutional cohort focused on paired resected initial/recurrent glioblastoma. The paired initial/recurrent cohort also had exome data available, which allowed for evaluation of multidimensional scaling analysis. Smaller selective glioblastoma cohorts are enriched for copy number subtypes that are associated with better survival, reflecting the selection of patients who do well enough to enter a clinical trial or who are deemed well enough to undergo resection at recurrence. Adding exome data to copy number data provides additional data reflective of outcome. The overall outcome for diffuse glioma patients is predicted by DNA structure at initial tumor resection. Molecular signature shifts across glioblastoma populations reflect the inherent bias of patient selection toward longer survival in clinical trials. Therefore it may be important to include molecular profiling, including copy number, when enrolling patients for clinical trials in order to balance arms and extrapolate relevance to the general glioblastoma population.
Short contact with nickel causes allergic contact dermatitis: an experimental study
Authors: M.G. Ahlström, J.P. Thyssen, T. Menné, K. Midander, A. Julander, C. Lidén, C.R. Johnsen, J.D. Johansen
Journal: British Journal of Dermatology (2018)

Knowledge about the required duration of exposure for elicitation of allergic nickel dermatitis in nickel-allergic individuals is limited. However, it often has been proposed that short skin contact is safe.To examine whether repeated skin contact with nickel over short time periods (3 × 10 min) can elicit allergic nickel dermatitis.Sixteen nickel-allergic adults and 10 controls were exposed to, respectively, nickel- and aluminium-containing discs on each volar forearm and on each earlobe for 3 × 10 min. One arm was pretreated for 24 h with sodium lauryl sulfate (SLS) 0·5% under occlusion before exposure. One aluminium and one nickel exposure site were clinically evaluated, and blood flow was measured with laser Doppler flowmetry at day 2 and day 4.Ten of 16 (63%) nickel-allergic participants developed allergic nickel dermatitis on SLS-pretreated arm skin and three of 16 (19%) developed it on normal skin on the earlobe. On the SLS-pretreated arms of nickel-allergic participants, blood flow increased significantly more on the nickel-exposed skin than on the aluminium-exposed skin on days 2 and 4. No change in clinical reactivity or blood flow was found on normal forearm skin in nickel-allergic participants or on any skin in controls.This experimental study showed that relatively short repeated skin contact (3 × 10 min) with metallic nickel elicits allergic nickel dermatitis in irritated skin and at sites with previous dermatitis. The results support the restrictions in current nickel regulation.
ADAP deficiency impairs megakaryocyte polarization with ectopic proplatelet release and causes microthrombocytopenia
Authors: Markus Spindler, Judith M. M. van Eeuwijk, Yvonne Schurr, Paquita Nurden, Bernhard Nieswandt, David Stegner, Annegret Reinhold, Markus Bender
Journal: Blood (2018)
Correction to: miR-153 suppresses IDO1 expression and enhances CAR T cell immunotherapy
Authors: Qian Huang, Jiajia Xi, Lei Wang, Xu Wang, Xiaodong Ma, Qipan Deng, Yong Lu, Munish Kumar, Zhiyuan Zhou, Ling Li, Zhaoyang Zeng, Ken H. Young, Qing Yi, Mingzhi Zhang, Yong Li
Journal: Journal of Hematology & Oncology (2018)

The original article [1] contains a spelling error in the authorship; the authors would like to note the correct spelling of the second author, Jiajia Xi.
Replacing the Pap Test With Screening Based on Human Papillomavirus Assays
Authors: L. Stewart Massad
Journal: JAMA (2018)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA HomeNew OnlineCurrent IssueFor Authors Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA journal