tbuckley/cabot-search huggingface dataset:
Junctional Adhesion Molecules in Cancer: A Paradigm for the Diverse Functions of Cell–Cell Interactions in Tumor Progression
Authors: Adam Lauko, Zhaomei Mu, David H. Gutmann, Ulhas P. Naik, Justin D. Lathia
Journal: Cancer Research (2020)

Tight junction (TJ) proteins are essential for mediating interactions between adjacent cells and coordinating cellular and organ responses. Initial investigations into TJ proteins and junctional adhesion molecules (JAM) in cancer suggested a tumor-suppressive role where decreased expression led to increased metastasis. However, recent studies of the JAM family members JAM-A and JAM-C have expanded the roles of these proteins to include protumorigenic functions, including inhibition of apoptosis and promotion of proliferation, cancer stem cell biology, and epithelial-to-mesenchymal transition. JAM function by interacting with other proteins through three distinct molecular mechanisms: direct cell-cell interaction on adjacent cells, stabilization of adjacent cell surface receptors on the same cell, and interactions between JAM and cell surface receptors expressed on adjacent cells. Collectively, these diverse interactions contribute to both the pro- and antitumorigenic functions of JAM. In this review, we discuss these context-dependent functions of JAM in a variety of cancers and highlight key areas that remain poorly understood, including their potentially diverse intracellular signaling networks, their roles in the tumor microenvironment, and the consequences of posttranslational modifications on their function. These studies have implications in furthering our understanding of JAM in cancer and provide a paradigm for exploring additional roles of TJ proteins.
Intention to Quit Vaping Among United States Adolescents
Authors: Tracy T. Smith, Georges J. Nahhas, Matthew J. Carpenter, Lindsay M. Squeglia, Vanessa A. Diaz, Adam M. Leventhal, Jennifer Dahne
Journal: JAMA Pediatrics (2020)

ally associated with single-feature SRT (β = -0.35;P = .05),with no association at 12 (β = 0.18; P = .65)or 18 months (β = -0.02;P = .96).Discussion | Toddler touch screen use is associated with faster single feature but not conjunction search, indicative of greater saliency-driven attention without impaired endogenous control.Results are specific to concurrent usage, suggesting recent touch screen experience may prime attention for exogenous control.Faster high-user SRTs in block 1 suggests a possible saliency bias coming into the task, rather than faster within-task learning.The real-world consequences, particularly when saliency and endogenous goals conflict (eg, focusing on schoolwork in a busy classroom), remain to be established.Future studies should use objective tracking of the child's complex media environment to assess the specificity across platforms, content, and type of use, as well as establish whether touch screen use has a causal influence on attention control.
FRI0115 Systemic lupus erythematosus in men
Authors: PV Voulgari, P Katsimbri, Y Alamanos, AA Drosos
Journal: Annals of the Rheumatic Diseases (2001)

<h3>Background</h3> <h3>Objectives</h3> To evaluate whether gender influences the clinical course and outcome in systemic lupus erythematosus (SLE). <h3>Methods</h3> Four hundred eighty-nine SLE patients were followed up at the University Hospital of Ioannina, Greece between 1981 and December 2000. These patients were reevaluated and the demographic, clinical, serological, radiological and therapeutic information were entered in a database. We divided our patients in two groups according to the gender. The disease activity and outcome were measured using the European Lupus Activity Score (ECLAM). <h3>Results</h3> There were 421 women and 68 men, ratio 7:1. There were no differences between men and women concerning age, disease duration, age at disease onset and disease follow up. Except for serositis in men, which was significantly more frequent (p = 0.01), organ involvement was not statistically different between the two groups. Laboratory evaluation showed that women had significantly higher levels of erythrocyte sedimentation rate compared to men (p = 0.001), while positive anti-nuclear antibodies and raised complement levels were more frequent in women (p = 0.08). There were no significant differences in ECLAM scores between the two groups as well as in the disease outcome for SLE patients. <h3>Conclusion</h3> SLE in men is a rare disease and the clinical expression and disease outcome seem to be similar to those described in women.
Intake of Dietary Fruit, Vegetables, and Fiber and Risk of Colorectal Cancer According to Molecular Subtypes: A Pooled Analysis of 9 Studies
Authors: Akihisa Hidaka, Tabitha A. Harrison, Yin Cao, Lori C. Sakoda, Richard Barfield, Marios Giannakis, Mingyang Song, Amanda I. Phipps, Jane C. Figueiredo, Syed H. Zaidi, Amanda E. Toland, Efrat L. Amitay, Sonja I. Berndt, Ivan Borozan, Andrew T. Chan, Steven Gallinger, Marc J. Gunter, Mark A. Guinter, Sophia Harlid, Heather Hampel, Mark A. Jenkins, Yi Lin, Victor Moreno, Polly A. Newcomb, Reiko Nishihara, Shuji Ogino, Mireia Obón-Santacana, Patrick S. Parfrey, John D. Potter, Martha L. Slattery, Robert S. Steinfelder, Caroline Y. Um, Xiaoliang Wang, Michael O. Woods, Bethany Van Guelpen, Stephen N. Thibodeau, Michael Hoffmeister, Wei Sun, Li Hsu, Daniel D. Buchanan, Peter T. Campbell, Ulrike Peters
Journal: Cancer Research (2020)

Abstract Protective associations of fruits, vegetables, and fiber intake with colorectal cancer risk have been shown in many, but not all epidemiologic studies. One possible reason for study heterogeneity is that dietary factors may have distinct effects by colorectal cancer molecular subtypes. Here, we investigate the association of fruit, vegetables, and fiber intake with four well-established colorectal cancer molecular subtypes separately and in combination. Nine observational studies including 9,592 cases with molecular subtypes for microsatellite instability (MSI), CpG island methylator phenotype (CIMP), and somatic mutations in BRAF and KRAS genes, and 7,869 controls were analyzed. Both case-only logistic regression analyses and polytomous logistic regression analyses (with one control set and multiple case groups) were used. Higher fruit intake was associated with a trend toward decreased risk of BRAF-mutated tumors [OR 4th vs. 1st quartile = 0.82 (95% confidence interval, 0.65–1.04)] but not BRAF-wildtype tumors [1.09 (0.97–1.22); P difference as shown in case-only analysis = 0.02]. This difference was observed in case–control studies and not in cohort studies. Compared with controls, higher fiber intake showed negative association with colorectal cancer risk for cases with microsatellite stable/MSI-low, CIMP-negative, BRAF-wildtype, and KRAS-wildtype tumors (Ptrend range from 0.03 to 3.4e-03), which is consistent with the traditional adenoma-colorectal cancer pathway. These negative associations were stronger compared with MSI-high, CIMP-positive, BRAF-mutated, or KRAS-mutated tumors, but the differences were not statistically significant. These inverse associations for fruit and fiber intake may explain, in part, inconsistent findings between fruit or fiber intake and colorectal cancer risk that have previously been reported. Significance: These analyses by colorectal cancer molecular subtypes potentially explain the inconsistent findings between dietary fruit or fiber intake and overall colorectal cancer risk that have previously been reported.
OP0007 MRI of the wrist and finger joints in inflammatory joint diseases at one year interval. MRI features to predict bone erosions
Authors: A Savnik, H Malmskov, HS Thomsen, LB Graff, H Nielsen, H Bliddal
Journal: Annals of the Rheumatic Diseases (2001)

<h3>Background</h3> Magnetic resonance imaging (MRI) has important applications in inflammatory joint diseases since it allows a direct visualisation of both bony and soft tissue. The wrist and finger joints are first affected in rheumatoid arthritis and of prime interest in predictive studies. Bone oedema is important MRI feature in inflammatory joint diseases and it has been suggested to be a forerunner of bone erosion. <h3>Objectives</h3> To compare the ability of the outlined synovial volumes before and after Gadodiamide injection, presence of bone marrow oedema, bone erosions and enhancement after Gadodiamide injection to predict progressions in bone erosions after 1 year follow up in patients with different types of inflammatory joint diseases. <h3>Methods</h3> 84 patients underwent MRI, laboratory and clinical examination at baseline and 1 year later. MRI of the wrist and finger joints was performed in 22 patients with rheumatoid arthritis less than 3 years (group 1), 18 patients with spondylarthropathies (group 2), 22 patients with more than 3 years duration of rheumatoid arthritis (group 3) and 20 patients with arthralgia (group 4). <h3>Results</h3> The total outlined synovial volumes in the finger joints before Gadodiamide injection and the number of bone erosions at baseline MRI were highly predictive of bone erosions one year later in patients with rheumatoid arthritis (group 1 and 3). The number of bones with erosions and oedema varied significantly between the patient groups. The strongest individual predictor of bone erosions at one year follow up was bone marrow oedema, if present at the wrist at baseline. Bone erosions on baseline MRI were in few cases reversible at follow up MRI. <h3>Conclusion</h3> The total synovial volume in the finger joints before contrast, the number of bone erosions and presence of bone oedema in the wrist at baseline seems to be predictive for the number of bone erosions 1 year later and may be used in screening. The importance of very early bone changes on MRI and the importance of these findings reversibility remain to be clarified. <h3>References</h3> Ostergaard M, Gideon P, Henriksen O, Lorenzen I. Synovial volume-a marker of disease severity in rheumatoid arthritis? Quantification by MRI. Scand J Rheumatol. 1994;23:197–202 McQueen FM. Magnetic resonance imaging in early inflammatory arthritis: what is its role? Rheumatology 2000;39:700–706 McGonagle D, Gibbon W, O'Connor P, Green M, Pease C, Ridgway J, Emery P. An anatomical explanation for good-prognosis rheumatoid arthritis. Lancet 1999;353:123–4
THU0117 The bias for th1 differentiation of rheumatoid arthritis t cells is characteristic of memory but not of naive t cells
Authors: A Skapenko, J Wendler, PE Lipsky, JR Kalden, H Schulze-Koops
Journal: Annals of the Rheumatic Diseases (2001)

<h3>Background</h3> Rheumatoid arthritis (RA) is likely to be driven by activated Th1 cells. In contrast, Th2 cells and their cytokines, in particular IL-4, are rarely found in RA. <h3>Objectives</h3> To determine whether memory or naive CD4<sup>pos</sup> T cells in RA manifest an intrinsic bias for Th1 differentiation. <h3>Methods</h3> Th differentiation was assessed in an <i>ex vivo</i> cell culture system in CD4<sup>pos</sup>, CD45RA<sup>pos</sup> (naive) and CD45RO <sup>pos</sup> (memory) T cells isolated from the peripheral blood from patients with active, early RA (mean disease duration &lt; 7 months) who had never been treated with disease modifying anti rheumatic drugs or corticosteroids. The phenotype of freshly isolated and effector cells was determined by flow cytometrical analysis of cytoplasmic cytokines. <h3>Results</h3> Th2 effectors could be induced from memory T cells in all healthy controls by stimulation with anti-CD28 and IL-4 but in only one third of the RA patients. Priming conditions that were optimal for the differentiation of Th2 effectors from memory T cells, e.g. priming with anti-CD28 and IL-4 in the absence of TCR-ligation, did not result in Th2 differentiation from resting naive T cells in any individual. In contrast to memory T cells, however, Th2 cells could be induced from naive T cells in all healthy donors and in all RA patients by priming with anti-CD3 in the presence of anti-CD28. <h3>Conclusion</h3> CD4<sup>pos</sup> memory T cells from the majority of patients with early RA manifest a deficiency in the capacity to differentiate into Th2 effectors. In contrast, naive T cells are capable of differentiating into Th2 cells with appropriate stimulation suggesting that the bias in Th1 differentiation of most RA patients is acquired during T cell maturation presumably in response to antigenic stimulation.
The Association of Veterans’ PSA Screening Rates With Changes in USPSTF Recommendations
Authors: Daniel J Becker, Temitope Rude, Dawn Walter, Chan Wang, Stacy Loeb, Huilin Li, Shannon Ciprut, Matthew Kelly, Steven B Zeliadt, Angela Fagerlin, Herbert Lepor, Scott Sherman, Joseph E Ravenell, Danil V Makarov
Journal: JNCI Journal of the National Cancer Institute (2020)

Abstract Background In 2012, the United States Preventative Services Task Force (USPSTF) formally recommended against all prostate-specific antigen (PSA) screening for prostate cancer. Our goal was to characterize PSA screening trends in the Veterans Health Administration (VA) before and after the USPSTF recommendation and to determine if PSA screening was more likely to be ordered based on a veteran’s race or age. Methods Using the VA Corporate Data Warehouse, we created 10 annual groups of PSA-eligible men covering 2009-2018. We identified all PSA tests performed in the VA to determine yearly rates of PSA screening. All statistical tests were 2-sided. Results The overall rate of PSA testing in the VA decreased from 63.3% in 2009 to 51.2% in 2018 (P &amp;lt; .001). PSA screening rates varied markedly by age group during our study period, with men aged 70-80 years having the highest initial rate and greatest decline (70.6% in 2009 to 48.4% in 2018, P &amp;lt; .001). Men aged 55-69 years had a smaller decline (65.2% in 2009 to 58.9% in 2018, P &amp;lt; .001) whereas the youngest men, aged 40-54 years, had an increase in PSA screening (26.2% in 2009 to 37.8% in 2018, P &amp;lt; .001). Conclusions In this analysis of PSA screening rates among veterans before and after the 2012 USPSTF recommendation against screening, we found that overall PSA screening decreased only modestly, continuing for more than one-half of the men in our study. Veterans of different races had similar screening rates, suggesting that VA care may minimize racial disparities. Veterans of varying ages experienced statistically significantly differences in PSA screening trends.
CDK1/2/5 inhibition overcomes IFNG-mediated adaptive immune resistance in pancreatic cancer
Authors: Jin Huang, Pan Chen, Ke Liu, Jiao Liu, Borong Zhou, Runliu Wu, Qiu Peng, Ze-Xian Liu, Changfeng Li, Guido Kroemer, Michael Lotze, Herbert Zeh, Rui Kang, Daolin Tang
Journal: Gut (2020)

Objective Adaptive immune resistance mediated by the cytokine interferon gamma (IFNG) still constitutes a major problem in cancer immunotherapy. We develop strategies for overcoming IFNG-mediated adaptive immune resistance in pancreatic ductal adenocarcinoma cancer (PDAC). Design We screened 429 kinase inhibitors for blocking IFNG-induced immune checkpoint (indoleamine 2,3-dioxygenase 1 (IDO1) and CD274) expression in a human PDAC cell line. We evaluated the ability of the cyclin-dependent kinase (CDK) inhibitor dinaciclib to block IFNG-induced IDO1 and CD274 expression in 24 human and mouse cancer cell lines as well as in primary cancer cells from patients with PDAC or ovarian carcinoma. We tested the effects of dinaciclib on IFNG-induced signal transducer and activator of transcription 1 activation and immunological cell death, and investigated the potential utility of dinaciclib in combination with IFNG for pancreatic cancer therapy in vivo, and compared gene expression levels between human cancer tissues with patient survival times using the Cancer Genome Atlas datasets. Results Pharmacological (using dinaciclib) or genetic (using shRNA or siRNA) inactivation of CDK1/2/5 not only blocks JUN-dependent immune checkpoint expression, but also triggers histone-dependent immunogenic cell death in immortalised or primary cancer cells in response to IFNG. This dual mechanism turns an immunologically ‘cold’ tumour microenvironment into a ‘hot’ one, dramatically improving overall survival rates in mouse pancreatic tumour models (subcutaneous, orthotopic and transgenic models). The abnormal expression of CDK1/2/5 and IDO1 was associated with poor patient survival in several cancer types, including PDAC. Conclusion CDK1/2/5 kinase activity is essential for IFNG-mediated cancer immunoevasion. CDK1/2/5 inhibition by dinaciclib provides a novel strategy to overcome IFNG-triggered acquired resistance in pancreatic tumour immunity.
Abstract IA11: Chemotherapy remodels the bladder cancer immune microenvironment
Authors: William Y. Kim
Journal: Clinical Cancer Research (2020)

Abstract In the United States urothelial carcinoma (UC) of the bladder is the 4th and 9th most frequent malignancy in men and women, respectively, with around 74,000 new cases and 16,000 deaths in 2017. High-grade (HG), muscle-invasive bladder tumors account for the majority of those deaths as patients with metastatic disease have a 5-year survival rate of only 15%. The current standard-of-care first-line therapy for metastatic disease is cisplatin-based combination chemotherapy or immune checkpoint inhibition in patients who are platinum ineligible. Novel immune checkpoint (IC) inhibitors, including anti-PD1 and anti-PD-L1, represent a paradigm shift in cancer therapy and have demonstrated substantial clinical benefits in patients with advanced UC. Despite the enthusiasm engendered by PD-1/PD-L1 axis blockade in metastatic UC, only 15-25% of patients treated in published trials had objective responses. Preliminary studies from our laboratory show that chemotherapy remodels the immune microenvironment of muscle-invasive bladder cancers. We have begun to investigate the mechanisms by which chemotherapy drives a heightened immune response using our recently described genetically engineered murine (GEM) models of bladder cancer. Citation Format: William Y. Kim. Chemotherapy remodels the bladder cancer immune microenvironment [abstract]. In: Proceedings of the AACR Special Conference on Bladder Cancer: Transforming the Field; 2019 May 18-21; Denver, CO. Philadelphia (PA): AACR; Clin Cancer Res 2020;26(15_Suppl):Abstract nr IA11.
Abstract 323: A Peptide Inhibitor of PTEN Improves Mouse Survival After Cardiac Arrest
Authors: Xiangdong Zhu, Jing Li, Huashan Wang, Chunpei Lee, Zhiyi Zhu, Terry Vanden Hoek
Journal: Circulation (2018)

Introduction: Prior works from our laboratory found that cooling protection after cardiac arrest is mediated by enhanced Akt activation and in cardiomyocyte the cooling protection can be reproduced using PTEN chemical inhibitor. The current study extend these works by designing a cell-permeable peptide, TAT-PTEN9c, which is more specific for PTEN. Hypothesis: We hypothesized that TAT-PTEN9c interferes with endogenous PTEN binding to cell membrane adaptor resulting in increased Akt activation, enhanced glucose utilization and improved mouse survival after cardiac arrest. Methods: Mouse cardiomyocytes were isolated from 1-3 day old mouse pups. Western blot was used to determine the efficacy of TAT-PTEN9c for Akt activation. The effect of TAT-PTEN9c on mouse survival after cardiac arrest was determined in a mouse model. TAT-PTEN9c (7.5 mg/kg) was given intravenously (IV) after CPR. As a measure of impaired glucose utilization, sorbitol content in heart and brain was determined by a fluorescence assay of NADH formation using sorbitol dehydrogenase and NAD + . Results: TAT-PTEN9c peptide enhanced Akt activation in mouse cardiomyocytes in a concentration-dependent manner. Akt phosphorylation was observed at 1 μM and further increased with 10 μM TAT-PTEN9c. TAT-PTEN9c blocked the binding of endogenous PTEN to MAGI2 in a co-immunoprecipitation assay, while TAT-PTEN3a control had no inhibitory effect. In a mouse model of cardiac arrest, survival was significantly increased in the TAT-PTEN9c treated group compared to saline controls at 4 h (10/15, 67% vs. 6/15, 40%, P &lt; 0.05) after CPR. TAT-PTEN9c improved MAP at both R30 min and R2h. The treated mice had increased Akt phosphorylation at R15 min in both heart and brain tissues with significantly decreased sorbitol content and reduced release of taurine and glutamate into blood, suggesting improved metabolic recovery and glucose utilization. Conclusion: TAT-PTEN9c can be used after CPR in a mouse SCA model to rapidly enhance Akt activation and decrease glucose shunting to the polyol pathway in critical organs, preventing osmotic injury and early cardiovascular collapse and death.
Abstract 15341: Coronary Arteriolar Vasomotor Dysfunction Precedes Cardiac Diastolic Dysfunction in Diabetic Cardiomyopathy
Authors: Carl W Tong, Heidi A Creed, Shu-Huai Tsai, Lih Kuo, Travis W Hein
Journal: Circulation (2019)

Diabetic cardiomyopathy (DbCM) consists of cardiac dysfunction and absence of significant occlusive coronary artery disease. Coronary microvascular dysfunction exists in DbCM, but the temporal link...
Vaccine Refusal and Measles Outbreaks in the US
Authors: Varun K. Phadke, Robert A. Bednarczyk, Saad B. Omer
Journal: JAMA (2020)

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
Role of C-Reactive Protein for Late-Onset Neonatal Sepsis
Authors: Brett Burstein, Marc Beltempo, Patricia S. Fontela
Journal: JAMA Pediatrics (2020)

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 Pediatrics 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 Pediatrics journal