tbuckley/cabot-search huggingface dataset:
Abstract 210: Soluble Tumor Necrosis Factor Receptors, Marker of Arterial Stiffness in Patients With Coronary Atherosclerosis
Authors: Sang-Hyun Kim, Hack-Lyoung Kim, Jae-Bin Seo, Joo-Hee Zo, Myung-A Kim
Journal: Circulation Research (2017)

Background: Soluble forms of tumor necrosis factor receptors (sTNFRs) are emerging target molecules of inflammatory disease. However, their role in vascular biology is not well known. This study was performed to investigate the association between serum concentrations of sTNFRs and arterial stiffness. Methods and Results: A total of 117 consecutive patients with suspected coronary artery disease (CAD) (63.6 ± 11.0 years; men, 65%) who were referred for invasive coronary angiography (ICA) were prospectively enrolled. Arterial blood sTNFR1 and sTNFR2 were measured using commercially available ELISA kits. Brachial-ankle pulse wave velocity (baPWV) measurements were made within 24 hours of blood sampling for sTNFRs measurement. Most of the patients (86.3%) had significant CAD (stenosis ≥ 50%) in ICA. In simple linear regression analyses, there were significant positive correlations of baPWV with sTNFR1 ( β = 0.483, P &lt; 0.001) and sTNFR2 ( β = 0.366, P &lt; 0.001). The baPWV values increased proportionally with increasing sTNFR1 ( P = 0.002) and sTNFR2 ( P = 0.076) tertiles. In multiple linear regression analyses, sTNFR1 ( β = 0.300, P &lt; 0.001) and sTNFR2 ( β = 0.206, P = 0.013) had independent association with baPWV even after controlling for potential confounders including age, gender, systolic blood pressure, diabetes mellitus and hypertension. Conclusions: Taken together, sTNFR1 and sTNFR2 were independently associated with baPWV in patients undergoing ICA. This study suggests that sTNFR1 and sTNFR2 can be considered therapeutic targets as well as new makers of arterial stiffness.
Abstract P227: Cardiovascular Disease (CVD) Risk Factors Have Opposite Associations with Abdominal Aortic Calcium (AAC) Density and Volume: The Multi-Ethnic Study of Atherosclerosis (MESA)
Authors: Nketi I Forbang, Joachim H Ix, Rosemay A Remigo-Baker, Matthew A Allison, Robyn L McClelland, Veit Sandfort, Michael H Criqui
Journal: Circulation (2016)

Background: AAC predicts future CVD events independently of CVD risk factors. The standard AAC score, the Agatston method, up-weights for greater calcium density, thus models higher calcium density as associated with increased CVD risk. We evaluated this model by investigating associations of CVD risk factors with AAC density and volume separately. Methods: Multivariable linear regression was used to investigate the independent cross-sectional associations of CVD risk factors, markers of inflammation, and potential promoters of calcification with AAC density and ln (AAC volume). AAC density was calculated as: Density = Agatston / (volume, mm 3 / CT scan slice thickness, mm). Agatston = area, mm 2 X density. Results: In 1413 MESA participants with prevalent AAC, mean age was 65 ± 9 years, mean AAC density was 3.0 ± 0.6, 52% were men, 44% were European-, 24% were Hispanic-, 18% were African-, and 14% were Chinese Americans (EA, HA, AA, and CA respectively). In fully adjusted models, older age was non-significantly associated with lower AAC density, but significantly associated with higher ln (AAC volume) (Figure). Compared to EA, we observed AAC density was significantly higher in CA, non-significantly higher HA and AA, but ln (AAC volume) was significantly lower in CA, HA, and AA. Also, smoking, alcohol use, family history of myocardial infarction, higher systolic blood pressure, elevated total cholesterol, and interluken-6 were significantly associated with higher ln (AAC volume), but not AAC density. Lastly, lower body mass index, higher serum HDL and calcium were significantly associated with higher AAC density, but associations with ln (AAC volume) were in the opposite direction. Conclusion: A greater burden of CVD risk factors was associated with higher AAC volume, but not AAC density. Thus, the Agatston method of up-weighting AAC scores for greater density in CVD risk prediction may be inappropriate. Investigators should evaluate separately associations of AAC density and volume with CVD events.
Oncogenic alterations detected by droplet digital PCR in patients with metastatic colorectal cancer resistant to cetuximab.
Authors: Rujiao Liu, Zhi-Yu Chen, Weijian Guo, Xiaodong Zhu, Mingzhu Huang, Wen Zhang, Xiaoying Zhao, Lixin Qiu, Xiaowei Zhang, Zhe Zhang, Chenchen Wang, Wenhua Li
Journal: Journal of Clinical Oncology (2019)

575 Background: Anti-EGFR therapy is the standard of care for metastatic colorectal cancer (mCRC) patients with RAS and BRAF genes wild type (wt). Secondary alterations of several genes have been identified as possibly resistant mechanisms to EGFR blockade, these including mutations of KRAS, NRAS, BRAF, MEK and EGFR ectodomain, as well as amplifications of HER2 and c-MET. In this study, we investigated alterations of these targeted genes for mCRC patients with acquired resistance to cetuximab treatment by using non-invasive droplet digital PCR (ddPCR) method within circulating DNA. Methods: We enrolled 38 RAS and BRAF wt patients, who progressed after failure of cetuximab contained regimens between Jul 2015 and Jan 2018. Plasma samples from all 38 patients were collected and detected for seven candidates (mutation of KRAS, NRAS, EGFR, BRAF, MEK, amplification of HER2, c-MET) by using ddPCR at the time of baseline, each evaluation by interval of 2 months and documented progression. All clinical parameters were collected simultaneously. Results: A total of 23 secondary alterations were found in 17 (17/38,44.7%) cetuximab resistant patients. The targeted gene alterations were detected as follows: 9 (9/23,39%) RAS mutations, 5 (22%) HER2 amplifications, 5 (22%) EGFR mutations, 2 (9%) c-MET amplifications, 1 (4%) BRAF and 1 MEK mutation. Among 17 patients, 6 patients had multiple alterations, including 2 patients with KRAS+EGFR mutations, 2 patients with HER2+c-MET co-amplifications and 2 patients with KRAS gene exon 2 and 3 multiple mutations. Primary sites were 15 left sides and 2 right sides, descending colon (12 cases) was the most common origins. Eleven patients were synchronous disease. Twelve patients received cetuximab as first line therapy, whereas 5 patients in the ≥ 2 nd line setting. All of these 17 patients, plasma levels of oncogenic alterations detected by ddPCR were showed dynamic changing and good agreement with tumor responding status. Conclusions: Oncogenic alterations detected by ddPCR were found in almost half mCRC patients resistant to cetuximab. Dynamic changes of specific alteration may facilitate making decisions for selection of anti-EGFR mAb during the treatment course.
Demographic Characteristics, Comorbidities, and Exacerbation Frequency Among Patients Enrolled in the Chronicle Study: A Real-World, Prospective, Observational Study of US, Subspecialist-Treated Adults with Severe Asthma
Authors: Weily Soong, Warner Carr, Bradley E. Chipps, Dennis K. Ledford, Njira Lugogo, Wendy C. Moore, Reynold A. Panettieri, Jennifer Trevor, Laura Belton, Frank Trudo, Christopher S. Ambrose
Journal: Journal of Allergy and Clinical Immunology (2019)
“Exercise pulmonary haemodynamics: a test in search of purpose.” J. Gerry Coghlan and Harm Jan Bogaard. <i>Eur Respir J</i> 2016; 47: 1315–1317.
Authors: Ville-Pekka Seppä, Anna Pelkonen, Anne Kotaniemi-Syrjänen, Jari Viik, Mika Mäkelä, L Pekka, Malmberg Eur
Journal: European Respiratory Journal (2016)
Rhinovirus Infection Augments Th1 Responses in Allergic Asthmatics
Authors: Lyndsey M. Muehling, Rachana Agrawal, Holly T. Carper, Thomas A.E. Platts-Mills, William W. Kwok, Peter W. Heymann, Judith A. Woodfolk
Journal: Journal of Allergy and Clinical Immunology (2019)
Matched Sibling Donor Hematopoietic Stem Cell Transplantation to Prevent Stroke in Children With Sickle Cell Anemia
Authors: Janet L. Kwiatkowski
Journal: JAMA (2019)

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 Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More 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 journal
Association of Single Nucleotide Polymorphisms in PTGS1 and PTGS2 with Aspirin-Induced Urticaria/Angioedema
Authors: Raquel Jurado-Escobar, Inmaculada Doña, James R. Perkins, Gador Bogas, Natalia Pérez-sanchez, Joan Bartra, María Isidoro-García, Maria Jose Torres Jaén, Cristobalina Mayorga, Jose A. Cornejo-Garcia
Journal: Journal of Allergy and Clinical Immunology (2019)
Pleiotropic Effects of PPARD Accelerate Colorectal Tumorigenesis, Progression, and Invasion
Authors: Yi Liu, Yasunori Deguchi, Rui Tian, Daoyan Wei, Ling Wu, Weidong Chen, Weiguo Xu, Min Xu, Fuyao Liu, Shen Gao, Jonathan C. Jaoude, Sarah P. Chrieki, Micheline J. Moussalli, Mihai Gagea, Jeffrey Morris, Russell R. Broaddus, Xiangsheng Zuo, Imad Shureiqi
Journal: Cancer Research (2019)

Abstract APC mutations activate aberrant β-catenin signaling to drive initiation of colorectal cancer; however, colorectal cancer progression requires additional molecular mechanisms. PPAR-delta (PPARD), a downstream target of β-catenin, is upregulated in colorectal cancer. However, promotion of intestinal tumorigenesis following deletion of PPARD in Apcmin mice has raised questions about the effects of PPARD on aberrant β-catenin activation and colorectal cancer. In this study, we used mouse models of PPARD overexpression or deletion combined with APC mutation (ApcΔ580) in intestinal epithelial cells (IEC) to elucidate the contributions of PPARD in colorectal cancer. Overexpression or deletion of PPARD in IEC augmented or suppressed β-catenin activation via up- or downregulation of BMP7/TAK1 signaling and strongly promoted or suppressed colorectal cancer, respectively. Depletion of PPARD in human colorectal cancer organoid cells inhibited BMP7/β-catenin signaling and suppressed organoid self-renewal. Treatment with PPARD agonist GW501516 enhanced colorectal cancer tumorigenesis in ApcΔ580 mice, whereas treatment with PPARD antagonist GSK3787 suppressed tumorigenesis. PPARD expression was significantly higher in human colorectal cancer–invasive fronts versus their paired tumor centers and adenomas. Reverse-phase protein microarray and validation studies identified PPARD-mediated upregulation of other proinvasive pathways: connexin 43, PDGFRβ, AKT1, EIF4G1, and CDK1. Our data demonstrate that PPARD strongly potentiates multiple tumorigenic pathways to promote colorectal cancer progression and invasiveness. Significance: These findings address long-standing, important, and unresolved questions related to the potential role of PPARD in APC mutation-dependent colorectal tumorigenesis by showing PPARD activation enhances APC mutation-dependent tumorigenesis.
Association Between April 20 Cannabis Celebration and Fatal Crashes
Authors: John A. Staples, Donald A. Redelmeier
Journal: JAMA Internal Medicine (2019)

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 Internal Medicine 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 Internal Medicine journal
Abstract 19741: Role of Ganglionated Plexus for the Maintenance of Atrial Fibrillation: Analysis of the Effect of Ganglionated Plexus Stimulation on the Atrial Activation Sequence
Authors: Shozo Kaneko, Hiroshige Yamabe, Hisanori Kanazawa, Miwa Ito, Yusuke Kanemaru, Takuya Kiyama, Kenichi Tsujita
Journal: Circulation (2017)

Background: It has been suggested that ganglionated plexus (GP) have a role to play in the initiation and maintenance of atrial fibrillation (AF) and is associated with the complex fractionated atr...
Collagen scaffolds functionalised with copper-eluting bioactive glass reduce infection and enhance osteogenesis and angiogenesis both in vitro and in vivo
Authors: Emily J. Ryan, Alan J. Ryan, Arlyng González-Vázquez, Anahí Philippart, Francesca E. Ciraldo, Christopher Hobbs, Valeria Nicolosi, Aldo R. Boccaccini, Cathal J. Kearney, Fergal J. O'Brien
Journal: Biomaterials (2019)
Resistance and Surrender — Remembering to Bow to Strength, Not Power
Authors: Jennifer Tsai
Journal: New England Journal of Medicine (2019)

Despite having conducted numerous speculum exams, the medical student had yet to submit to her own first pelvic exam. In college, she had been sexually assaulted in her dorm room, and the idea of the exam brought up ferocious anxiety, metallic bile, fear, and refusal.
Easy-to-build and affordable continuous positive airway pressure CPAP device for adult patients in low-income countries
Authors: Ramon Farré, Josep M. Montserrat, Gorka Solana, David Gozal, Daniel Navajas
Journal: European Respiratory Journal (2019)

<b>Teams from developed and developing countries have collaborated to design and test a low-cost, high-performance device to apply continuous positive airway pressure for treating patients in low-income countries</b>http://ow.ly/Cllj30nMGQq
AVID200, a Potent Trap for TGF-β Ligands Inhibits TGF-β1 Signaling in Human Myelofibrosis
Authors: Lilian Varricchio, John Mascarenhas, Anna Rita Migliaccio, Maureen O'Connor-McCourt, Gilles Tremblay, Jean-François Denis, Camelia Iancu-Rubin, Ronald Hoffman
Journal: Blood (2018)
Acidification of Tumor at Stromal Boundaries Drives Transcriptome Alterations Associated with Aggressive Phenotypes
Authors: Nazanin Rohani, Liangliang Hao, Maria S. Alexis, Brian A. Joughin, Konstantin Krismer, Mira N. Moufarrej, Anthony R. Soltis, Douglas A. Lauffenburger, Michael B. Yaffe, Christopher B. Burge, Sangeeta N. Bhatia, Frank B. Gertler
Journal: Cancer Research (2019)

Acidosis is a fundamental feature of the tumor microenvironment, which directly regulates tumor cell invasion by affecting immune cell function, clonal cell evolution, and drug resistance. Despite the important association of tumor microenvironment acidosis with tumor cell invasion, relatively little is known regarding which areas within a tumor are acidic and how acidosis influences gene expression to promote invasion. Here, we injected a labeled pH-responsive peptide to mark acidic regions within tumors. Surprisingly, acidic regions were not restricted to hypoxic areas and overlapped with highly proliferative, invasive regions at the tumor-stroma interface, which were marked by increased expression of matrix metalloproteinases and degradation of the basement membrane. RNA-seq analysis of cells exposed to low pH conditions revealed a general rewiring of the transcriptome that involved RNA splicing and enriched for targets of RNA binding proteins with specificity for AU-rich motifs. Alternative splicing of Mena and CD44, which play important isoform-specific roles in metastasis and drug resistance, respectively, was sensitive to histone acetylation status. Strikingly, this program of alternative splicing was reversed
Immunological nomograms predicting prognosis and guiding adjuvant chemotherapy in stage II colorectal cancer.
Authors: Junjie Peng, Yaqi Li, Yang Feng
Journal: Journal of Clinical Oncology (2019)

499 Background: The type, abundance, and location of tumor-infiltrating lymphocytes (TILs) have been associated with prognosis in colorectal cancer. The objective of this study was to assess the prognostic role of TILs and develop a nomogram for accurate prognostication of stage II colorectal cancer. Methods: Immunohistochemistry was conducted to assess the densities of intraepithelial and stromal CD3+, CD8+, CD45RO+ and FOXP3+ TILs, and to estimate PD-L1 expression in tumor cells for 168 patients with stage II colorectal cancer. The prognostic roles of these features were evaluated using COX regression model, and nomograms were established to stratify patients into low and high-risk groups and compare the benefit from adjuvant chemotherapy. Results: In univariate analysis, patients with high intraepithelial or stromal CD3+, CD8+, CD45RO+ and FOXP3+ TILs were associated significantly with better relapse-free survival (RFS) and overall survival (OS), except for stromal CD45RO+ TILs, whereas PD-L1 expression wasn't associated with RFS or OS. In multivariate analysis, patients with high intraepithelial CD3+ and stromal FOXP3+ TILs were associated with better RFS (p &lt; 0.001 and p = 0.032, respectively), while only stromal FOXP3+ TILs was an independent prognostic factor for OS (p = 0.031). The nomograms were well calibrated and showed a c-index of 0.751 and 0.757 for RFS and OS, respectively. After stratifying into low and high-risk groups, the high-risk group exhibited a better OS from adjuvant chemotherapy (3-year OS of 81.9% v 34.3%, p = 0.006). Conclusions: These results may help improve the prognostication of stage II colorectal cancer and identify a high-risk subset of patients who appeared to benefit from adjuvant chemotherapy.
Prospective Validation of The RAPID Clinical Risk Prediction Score in Patients with Pleural Infection: The Pleural Infection Longitudinal Outcome Study (PILOT)
Authors: J P Corcoran, I Psallidas, S Gerry, F Piccolo, C F Koegelenberg, T Saba, C Daneshvar, I Fairbairn, R Heinink, A West, A E Stanton, J Holme, J A Kastelik, H Steer, N J Downer, M Haris, E H Baker, C F Everett, J Pepperell, T Bewick, L B Yarmus, F Maldonado, B Khan, A Hart-Thomas, G Hands, G Warwick, M Munavvar, A Guhan, M Shahidi, Z E Pogson, L Dowson, N Ward, J Saba, C Read, R Bhatnagar, R J Hallifax, M Dobson, R Shaw, E L Hedley, A Sabia, B Robinson, G S Collins, H E Davies, L Yu, N A Maskell, R F Miller, N M Rahman
Journal: American Journal of Respiratory and Critical Care Medicine (2018)
Baseline RANKL:OPG ratio and markers of bone and cartilage degradation predict annual radiological progression over 11 years in rheumatoid arthritis
Authors: L. H. D. van Tuyl, A. E. Voskuyl, M. Boers, P. Geusens, R. B. M. Landewe, B. A. C. Dijkmans, W. F. Lems
Journal: Annals of the Rheumatic Diseases (2010)

<h3>Objective</h3> To determine to what extent baseline measurements of the ratio receptor activator of nuclear factor-κB ligand (RANKL):osteoprotegerin (OPG) and C-terminal cross linking of type-I and type-II (CTX-I and CTX-II), in addition to traditional markers of disease severity, could predict annual radiological progression. <h3>Methods</h3> A cohort of 155 patients with early, active, untreated rheumatoid arthritis (RA) who participated in the Combination Therapy in Early Rheumatoid Arthritis trial (COBRA trial) was followed up for 11 years. Urine was sampled at baseline and after 3 months from the start of treatment and analysed for CTX-I and CTX-II. Baseline serum samples were analysed for RANKL and OPG. Available traditional markers of disease severity included baseline measurements of erythrocyte sedimentation rate, rheumatoid factor and baseline radiological damage. A digital database of frequent radiographs was available, scored according to the Sharp/van der Heijde method. Individual annual progression rates were calculated and used as outcome variable. Multiple linear regression analyses identified the strongest predictors of annual radiological progression. <h3>Results</h3> In multivariable analyses the RANKL:OPG ratio and CTX-I or CTX-II proved to be independent predictors of annual radiological damage over 11 years. The prediction of annual radiological progression was strongest when the RANKL:OPG ratio and CTX-I or CTX-II were evaluated in the same model (36–39% explained variance). Adding the effect of treatment at 3 months to the baseline models improved the predictive ability of the models up to 44–46%. <h3>Conclusion</h3> Unfavourable baseline levels of the RANKL:OPG ratio as well as CTX-I and CTX-II in patients with early, active, untreated RA are strong independent predictors of rapid and persistent damage progression over the 11-year follow-up. Early improvement in bone markers by treatment predicts a better outcome.