tbuckley/cabot-search huggingface dataset:
Development and Validation of a Simple-to-Use Nomogram for Predicting 5-, 10-, and 15-Year Survival in Asymptomatic Adults Undergoing Coronary Artery Calcium Scoring
Authors: Bríain Ó Hartaigh, Heidi Gransar, Tracy Callister, Leslee J. Shaw, Joshua Schulman-Marcus, Wijnand J. Stuijfzand, Valentina Valenti, Iksung Cho, Jackie Szymonifka, Fay Y. Lin, Daniel S. Berman, Hyuk-Jae Chang, James K. Min
Journal: JACC. Cardiovascular imaging (2017)

The purpose of this study was to develop and validate a simple-to-use nomogram for prediction of 5-, 10-, and 15-year survival among asymptomatic adults. Simple-to-use prognostication tools that incorporate robust methods such as coronary artery calcium scoring (CACS) for predicting near-, intermediate- and long-term mortality are warranted. In a consecutive series of 9,715 persons (mean age: 53.4 ± 10.5 years; 59.3% male) undergoing CACS, we developed a nomogram using Cox proportional hazards regression modeling that included: age, sex, smoking, hypertension, dyslipidemia, diabetes, family history of coronary artery disease, and CACS. We developed a prognostic index (PI) summing the number of risk points corresponding to weighted covariates, which was used to configure the nomogram. Validation of the nomogram was assessed by discrimination and calibration applied to a separate cohort of 7,824 adults who also underwent CACS. A total of 936 and 294 deaths occurred in the derivation and validation sets at a median follow-up of 14.6 years (interquartile range: 13.7 to 15.5 years) and 9.4 years (interquartile range: 6.8 to 11.5 years), respectively. The developed model effectively predicted 5-, 10-, and 15-year probability of survival. The PI displayed high discrimination in the derivation and validation sets (C-index 0.74 and 0.76, respectively), indicating suitable external performance of our nomogram model. The predicted and actual estimates of survival in each dataset according to PI quartiles were similar (though not identical), demonstrating improved model calibration. A simple-to-use nomogram effectively predicts 5-, 10- and 15-year survival for asymptomatic adults undergoing screening for cardiac risk factors. This nomogram may be considered for use in clinical care.
Microarray analysis of bone marrow lesions in osteoarthritis demonstrates upregulation of genes implicated in osteochondral turnover, neurogenesis and inflammation
Authors: Anasuya Kuttapitiya, Lena Assi, Ken Laing, Caroline Hing, Philip Mitchell, Guy Whitley, Abiola Harrison, Franklyn A Howe, Vivian Ejindu, Christine Heron, Nidhi Sofat
Journal: Annals of the Rheumatic Diseases (2017)

<h3>Objective</h3> Bone marrow lesions (BMLs) are well described in osteoarthritis (OA) using MRI and are associated with pain, but little is known about their pathological characteristics and gene expression. We evaluated BMLs using novel tissue analysis tools to gain a deeper understanding of their cellular and molecular expression. <h3>Methods</h3> We recruited 98 participants, 72 with advanced OA requiring total knee replacement (TKR), 12 with mild OA and 14 non-OA controls. Participants were assessed for pain (using Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC)) and with a knee MRI (using MOAKS). Tissue was then harvested at TKR for BML analysis using histology and tissue microarray. <h3>Results</h3> The mean (SD) WOMAC pain scores were significantly increased in advanced OA 59.4 (21.3) and mild OA 30.9 (20.3) compared with controls 0.5 (1.28) (p&lt;0.0001). MOAKS showed all TKR tissue analysed had BMLs, and within these lesions, bone marrow volume was starkly reduced being replaced by dense fibrous connective tissue, new blood vessels, hyaline cartilage and fibrocartilage. Microarray comparing OA BML and normal bone found a significant difference in expression of 218 genes (p&lt;0.05). The most upregulated genes included stathmin 2, thrombospondin 4, matrix metalloproteinase 13 and Wnt/Notch/catenin/chemokine signalling molecules that are known to constitute neuronal, osteogenic and chondrogenic pathways. <h3>Conclusion</h3> Our study is the first to employ detailed histological analysis and microarray techniques to investigate knee OA BMLs. BMLs demonstrated areas of high metabolic activity expressing pain sensitisation, neuronal, extracellular matrix and proinflammatory signalling genes that may explain their strong association with pain.
Estimating the causal influence of body mass index on risk of Parkinson disease: A Mendelian randomisation study
Authors: Alastair J. Noyce, Demis A. Kia, Gibran Hemani, Aude Nicolas, T. Ryan Price, Eduardo De Pablo-Fernandez, Philip C. Haycock, Patrick A. Lewis, Thomas Foltynie, George Davey Smith, Anette Schrag, Andrew J. Lees, John Hardy, Andrew Singleton, Mike A. Nalls, Neil Pearce, Debbie A. Lawlor, Nicholas W. Wood
Journal: PLoS Medicine (2017)

Background Both positive and negative associations between higher body mass index (BMI) and Parkinson disease (PD) have been reported in observational studies, but it has been difficult to establish causality because of the possibility of residual confounding or reverse causation. To our knowledge, Mendelian randomisation (MR)—the use of genetic instrumental variables (IVs) to explore causal effects—has not previously been used to test the effect of BMI on PD. Methods and findings Two-sample MR was undertaken using genome-wide association (GWA) study data. The associations between the genetic instruments and BMI were obtained from the GIANT consortium and consisted of the per-allele difference in mean BMI for 77 independent variants that reached genome-wide significance. The per-allele difference in log-odds of PD for each of these variants was estimated from a recent meta-analysis, which included 13,708 cases of PD and 95,282 controls. The inverse-variance weighted method was used to estimate a pooled odds ratio (OR) for the effect of a 5-kg/m2 higher BMI on PD. Evidence of directional pleiotropy averaged across all variants was sought using MR–Egger regression. Frailty simulations were used to assess whether causal associations were affected by mortality selection. A combined genetic IV expected to confer a lifetime exposure of 5-kg/m2 higher BMI was associated with a lower risk of PD (OR 0.82, 95% CI 0.69–0.98). MR–Egger regression gave similar results, suggesting that directional pleiotropy was unlikely to be biasing the result (intercept 0.002; p = 0.654). However, the apparent protective influence of higher BMI could be at least partially induced by survival bias in the PD GWA study, as demonstrated by frailty simulations. Other important limitations of this application of MR include the inability to analyse non-linear associations, to undertake subgroup analyses, and to gain mechanistic insights. Conclusions In this large study using two-sample MR, we found that variants known to influence BMI had effects on PD in a manner consistent with higher BMI leading to lower risk of PD. The mechanism underlying this apparent protective effect warrants further study.
Consistent Terminology Needed for Estimation of Outcomes of Prematurity
Authors: Shilpi Chabra
Journal: JAMA Pediatrics (2017)

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
Managing Cancer and Living Meaningfully (CALM): A Randomized Controlled Trial of a Psychological Intervention for Patients With Advanced Cancer
Authors: Gary Rodin, Christopher Lo, Anne Rydall, Joanna Shnall, Carmine Malfitano, Aubrey Chiu, Tania Panday, Sarah Watt, Ekaterina An, Rinat Nissim, Madeline Li, Camilla Zimmermann, Sarah Hales
Journal: Journal of Clinical Oncology (2018)

Purpose Individuals with advanced cancer experience substantial distress in response to disease burden and impending mortality. Managing Cancer And Living Meaningfully (CALM) is a novel, brief, manualized psychotherapeutic intervention intended to treat and prevent depression and end-of-life distress in patients with advanced cancer. We conducted a randomized controlled trial to compare CALM with usual care (UC) in this population. Methods Patients with advanced cancer were recruited from outpatient oncology clinics at a comprehensive cancer center into an unblinded randomized controlled trial. Permuted block randomization stratified by Patient Health Questionnaire-9 depression score allocated participants to CALM plus UC or to UC alone. Assessments of depressive symptoms (primary outcome), death-related distress, and other secondary outcomes were conducted at baseline, 3 months (primary end point), and 6 months (trial end point). Analyses were by intention to treat. Analysis of covariance was used to test for outcome differences between groups at follow-up, controlling for baseline. Mixed-model results are reported. Results Participants (n = 305) were recruited between February 3, 2012, and March 4, 2016, and randomly assigned to CALM (n = 151) or UC (n = 154). CALM participants reported less-severe depressive symptoms than UC participants at 3 months (Δ = 1.09; P = .04; Cohen’s d = 0.23; 95% CI, 0.04 to 2.13) and at 6 months (Δ = 1.29; P = .02; d = 0.29; 95% CI, 0.24 to 2.35). Significant findings for greater end-of-life preparation at 6 months also favored CALM versus UC. No adverse effects were identified. Conclusion Findings suggest that CALM is an effective intervention that provides a systematic approach to alleviating depressive symptoms in patients with advanced cancer and addresses the predictable challenges these patients face.
Identification of Immune Phenotypes Associated with Improved Progression Free and Overall Survival for Patients with Multiple Myeloma Treated with Autologous Hematopoietic Cell Transplantation
Authors: Christine M. Ho, Theresa Hahn, Paul K. Wallace, Yali Zhang, Ahmad Fora, George L. Chen, Sarah A. Holstein, Patrick Mellors, Benjamin McCarthy, Sophia R. Balderman, Philip L. McCarthy
Journal: Blood (2016)
Correlation of Serum Ferritin Levels with Liver and Heart Mri T2 and Liver Iron Concentration in Beta Thalassemia Intermediate Patients: A Contemporary Issue
Authors: Mehran Karimi, Fatemeh Amirmoezi, Sezaneh Haghpanah, Seyed pouria Ostad, Mehrzad Lotfi, Sepideh Sefidbakht, Shahed Rezaian
Journal: Blood (2016)
Does frailty affect response to chemotherapy in older men with metastatic castration-resistant prostate cancer?
Authors: Shabbir M.H. Alibhai, Tharsika Manokumar, Salman Aziz, Faraz Rizvi, Henriette Breunis, Anthony M. Joshua
Journal: Journal of Clinical Oncology (2015)

e20528 Background: There is increasing recognition that frailty, which is common in older adults with cancer, may negatively impact treatment and survival. Few data exist, however, in specific disease settings. We examined the impact of frailty on elder-relevant outcomes in men with metastatic castration-resistant prostate cancer (mCRPC). Methods: Men aged 65+ with mCRPC starting first-line chemotherapy with docetaxel and prednisone were enrolled in an observational study. Frailty was evaluated with the Vulnerable Elders Survey (VES-13) questionnaire. Three main elder-relevant outcomes were assessed: physical function (timed up and go (TUG) test, timed chair stands, and grip strength), functional status (OARS-IADL), and quality of life (QOL, with the FACT-P and FACT-G for prostate-specific and general QOL, respectively). Assessments were completed before each cycle of chemotherapy. Pre-post within-group comparisons were done using student’s T-tests and linear regression, stratified by frailty status. Results: 44 patients (mean age 75) receiving chemotherapy were enrolled, of whom 56% were frail by VES-13. Frail men had worse physical function, functional status, and QOL at baseline than non-frail men (all p < 0.05). From baseline to end-of-study, functional status remained stable and both general and prostate-specific QOL improved in the majority of men. TUG scores and grip strength were stable over time in the majority of men. For all of these outcomes the trajectory was similar among frail and non-frail men. Only timed chair stand performance differed by frailty status over time; non-frail men demonstrated improvement whereas frail men declined by end-of-study. Frailty status at baseline (frail/non-frail) remained stable in the vast majority of men at chemotherapy completion. Conclusions: Contrary to our hypothesis, frail older men with mCRPC had similar changes during docetaxel-based chemotherapy in most areas of physical function, functional status, and QOL compared to non-frail older men. Although chemotherapy appears to be well-tolerated in these men, confirmation in a larger dataset is required. Importantly, the VES-13 may not be a suitable frailty measure in this population.
Is Telomere Length shortening a Predictive Biomarker for Cancer Risk in Ulcerative Colitis?
Authors: J O'Sullivan, C O'Riain, J Gorman, D Keegan, H Mulcahy, J Hyland, D Fennelly, K Sheahan, D O'Donoghue
Journal: Endoscopy (2004)

Aims: Neoplastic progression in Ulcerative Colitis (UC) is accompanied by genetic abnormalities and telomere shortening is a candidate for producing such genomic instability. Our overall goal is to examine if telomere shortening can distinguish UC patients at greatest risk of dysplasia/Colorectal Cancer (CRC). We hypothesize that continuous telomere length shortening may correlate with UC progression.
Frequency of use and outcome of surgical resection in the management of malignant mesothelioma in a community-based population: Results in 5,937 patients
Authors: R. M. Flores, E. Riedel, J. S. Donington, L. Krug, K. Rosenzweig, P. Adusumilli, M. Carbone, V. W. Rusch, H. I. Pass
Journal: Journal of Clinical Oncology (2009)

7510 Background: Multimodality therapy of mesothelioma patients treated at specialized tertiary hospitals report surgical resection rates of 42% (Flores RM et al. Prognostic Factors in the Treatment of Malignant Pleural Mesothelioma at a Large Tertiary Referral Center. J Thorac Oncol 2007;2(10):957–965.). Treatment strategies in the community are less well defined and surgical expertise is not readily available. We undertook this study to evaluate the rate of surgical resection and its association with survival in a non-tertiary based population. Methods: The Surveillance, Epidemiology, and End Results (SEER) database was searched from 1990 - 2004. Variables analyzed included age, sex, race, year of diagnosis, laterality, vital status, stage, surgery, and reasons for no surgery. The association of resection on overall survival was estimated by the Kaplan-Meier method and examined in a Cox proportional hazards model adjusting for covariates. Results: Pathologically proven malignant pleural mesothelioma was identified in 5,937 patients: 1,166 women, 4,771 men; median age was 70 years. Surgical resection rate was 11% (n=636). Univariate analysis demonstrated a median survival of 13 months with surgical resection and a median survival of 7 months in the non-resected group (p&lt;0.0001). Multivariate analysis demonstrated improved survival for surgically resected patients (HR 0.7, p&lt;0.0001), controlling for age, gender, and stage. Conclusions: Surgical resection was associated with improved survival when controlling for age, stage, and gender. However, the rate of surgical resection was much lower in the community when compared to tertiary referral centers. Treatment efforts should be focused on a multidisciplinary approach which includes surgical evaluation. No significant financial relationships to disclose.
Allele-Specific Silencing of Mutant mRNA Rescues Ultrastructural and Arrhythmic Phenotype in Mice Carriers of the R4496C Mutation in the Ryanodine Receptor Gene ( <i>RYR2</i> )
Authors: Rossana Bongianino, Marco Denegri, Andrea Mazzanti, Francesco Lodola, Alessandra Vollero, Simona Boncompagni, Silvia Fasciano, Giulia Rizzo, Damiano Mangione, Serena Barbaro, Alessia Di Fonso, Carlo Napolitano, Alberto Auricchio, Feliciano Protasi, Silvia G. Priori
Journal: Circulation Research (2017)

Mutations in the cardiac Ryanodine Receptor gene (RYR2) cause dominant catecholaminergic polymorphic ventricular tachycardia (CPVT), a leading cause of sudden death in apparently healthy individuals exposed to emotions or physical exercise.We investigated the efficacy of allele-specific silencing by RNA interference to prevent CPVT phenotypic manifestations in our dominant CPVT mice model carriers of the heterozygous mutation R4496C in RYR2.We developed an in vitro mRNA and protein-based assays to screen multiple siRNAs for their ability to selectively silence mutant RYR2-R4496C mRNA over the corresponding wild-type allele. For the most performant of these siRNAs (siRYR2-U10), we evaluated the efficacy of an adeno-associated serotype 9 viral vector (AAV9) expressing miRYR2-U10 in correcting RyR2 (Ryanodine Receptor type 2 protein) function after in vivo delivery by intraperitoneal injection in neonatal and adult RyR2R4496C/+ (mice heterozygous for the R4496C mutation in the RyR2) heterozygous CPVT mice. Transcriptional analysis showed that after treatment with miRYR2-U10, the ratio between wild-type and mutant RYR2 mRNA was doubled (from 1:1 to 2:1) confirming the ability of miRYR2-U10 to selectively inhibit RYR2-R4496C mRNA, whereas protein quantification showed that total RyR2 was reduced by 15% in the heart of treated mice. Furthermore, AAV9-miRYR2-U10 effectively (1) reduced isoproterenol-induced delayed afterdepolarizations and triggered activity in infected cells, (2) reduced adrenergically mediated ventricular tachycardia in treated mice, (3) reverted ultrastructural abnormalities of junctional sarcoplasmic reticulum and transverse tubules, and (4) attenuated mitochondrial abnormalities.The study demonstrates that allele-specific silencing with miRYR2-U10 prevents life-threatening arrhythmias in CPVT mice, suggesting that the reduction of mutant RyR2 may be a novel therapeutic approach for CPVT.
ARHGAP18 Downregulation by miR-200b Suppresses Metastasis of Triple-Negative Breast Cancer by Enhancing Activation of RhoA
Authors: Brock Humphries, Zhishan Wang, Yunfei Li, Jing-Ru Jhan, Yiguo Jiang, Chengfeng Yang
Journal: Cancer Research (2017)

Rho GTPases activated in cancer cells drive proliferation, migration, and metastasis. Thus, RhoGAP proteins, which negatively regulate Rho GTPases, are generally thought to function as tumor suppressors. Here this expectation was challenged by characterization of ARHGAP18, a RhoGAP family member that is selectively overexpressed in highly migratory triple-negative breast cancer (TNBC) cells. In human breast tumors, higher ARHGAP18 levels associated with worse overall survival, recurrence-free survival, and metastasis-free survival. In TNBC cells, ARHGAP18 deletion increased RhoA activation but reduced growth, migration, and metastatic capacity. Mechanistic investigations revealed that ARHGAP18 levels were controlled by miR-200b, the enforced expression of which was sufficient to activate RhoA, enhanced formation of focal adhesions and actin stress fibers, and reduced migration and metastasis. Enforced elevation of ARHGAP18 where miR-200b was stably expressed reduced RhoA activity but increased cell migration. Pharmacologic inhibition of the Rho effector kinase ROCK blocked RhoA signaling and reversed the inhibitory effect of miR-200b on cell migration. Finally, ARHGAP18 overexpression or ROCK inhibition was sufficient to overcome metastatic blockade by miR-200b. Taken together, these results define opposing roles for oncogenic ARHGAP18 and tumor suppressive miR-200b in determining TNBC cell migration and metastatic prowess. Cancer Res; 77(15); 4051-64. ©2017 AACR.
Abstract 127: Txnip-Mediated NLRP3 Inflammasome Activation as a Novel Mechanism of Myocardial Ischemia-Reperfusion Injury
Authors: Yi Liu, Lijian Zhang, Yan Qu, Chao Gao, Jingyi Liu, Wenjun Yan, Peilin Liu, Lu Sun, Lu Yang, Haichang Wang, Ling Tao
Journal: Circulation Research (2012)

As an inhibitor of the antioxidant thioredoxin, thioredoxin-interacting protein (Txnip) is linked to insulin resistance. NLRP3 inflammasome, a major regulator of innate immunity, has been reported to be activated by Txnip, thus contributing to the pathogenesis of type 2 diabetes mellitus. However, the role of Txnip and its NLRP3 inflammasome activation in the myocardial ischemia/reperfusion (MI/R) injury has not been previously investigated. C57BL/6J mice were subjected to 30 min of ischemia and 3 or 24 hrs of reperfusion. The ischemic heart exhibited increased Txnip and NLRP3 expressions, increased interaction between Txnip and NLRP3 (by immunoprecipitation, 1.8-fold increase over sham), and increased IL-1β, IL-18 and caspase-1 expressions (%increase: 80%, 77% and 110%, respectively) (n=8, all P &lt;0.05). Compared with vehicle group, those mice either receiving intramyocardial small-interfering RNA (siRNA) injection to specifically knockdown the myocardial NLRP3 or intraperitoneal injection of the inflammasome inhibitor (BAY 11-7082) exhibited significantly improved cardiac function (by 28% and 25%), decreased the infarct size (by 40% and 38%), and decreased the cardiomyocytes apoptosis (all P &lt;0.05). NLRP3 knockdown or inflammasome inhibitor also decreased the inflammatory cells infiltration (macrophages and neutrophils) and cytokines (TNF-α, INF-γ and IL-6) production (all P &lt;0.05). To elucidate the role of Txnip in the NLRP3 activation in MI/R, intramyocardial injection of Txnip siRNA was performed to specifically knockdown the myocardial Txnip expression. Compared with vehicle, the Txnip knockdown significantly decreased Txnip/NLRP3 interaction and NLRP3activation as evidenced by lower expressions of IL-1β and caspase-1, decreased inflammatory cells infiltration and cytokines expressions, and consequently decreased the myocardial infarct size and increased the heart function (all P &lt;0.05). Collectively, we demonstrated for the first time that Txnip mediatedNLRP3 inflammasome activation is a novel mechanism of MI/R injury. Interventions targeted to blocking the activation of NLRP3 by inhibiting Txnip may have therapeutic potential for preventing MI/R injury.