tbuckley/cabot-search huggingface dataset:
Abstract MP84: Trans-ethnic Meta-analysis of Exome Chip Data Reveals Novel Low-frequency Variants Contributing to Central Adiposity
Authors: Kristin L Young, Anne Justice, Tugce Karaderi, Heather Highland, Mariaelisa Graff, Valerie Turcot, Paul Auer, Nancy Heard-Costa, Claudia Schurmann, Yingchang Lu, Dorota Pasko, L Adrienne Cupples, Caroline Fox, Thomas Winkler, Robert Scott, Mark McCarthy, Karen Mohlke, Ruth JF Loos, Kari North, Ingrid Borecki, Cecilia Lindgren
Journal: Circulation (2016)

Central adiposity is a leading risk factor for cardiovascular disease, and genetic factors contribute both to fat distribution, measured as waist-to-hip ratio adjusted for BMI (WHRa), and to differences in central adiposity prevalence. To date, 49 loci have been associated with WHRa, based on studies of common [minor allele frequency (MAF) ≥5%] single nucleotide variants (SNVs), primarily in European descent populations. Our aim was to identify low frequency (LFV: MAF &lt;5%) and rare (RV: MAF &lt;1%) coding variants associated with WHRa using Exome-Chip data from 344,369 individuals of European (84%), South Asian (8%), African (5%), East Asian(2%), and Hispanic/Latino (1%) ancestry. We performed fixed effects meta-analyses of study-specific WHRa associations stratified by sex and ancestry and then combined across strata for both SNV and gene-based results. We used a strict definition of variants annotated as damaging by 5 algorithms to perform gene-based analyses using the sequence kernel association test (SKAT). Analyses included up to 284,499 SNVs (218,195 with MAF&lt;5%), and 15,063 genes with at least one SNV that met our inclusion criteria. Five LFVs reached chip-wide significance (CWS: P&lt;2.5E-7) in our all ancestry sex-combined analyses, including one novel non-synonymous LFV in RAPGEF3 [MAF=0.01, β (SE) = -0.09 (0.012), P=1.28E-13]. In addition, one novel RV reached CWS in men for UGGT2 [MAF&lt;0.01, β (SE) = -0.142 (0.025), P=9.71E-9], and one RV reached CWS in women for ACVR1C [MAF&lt;0.01, β (SE) = -0.09 (0.018), P=1.09E-7]. Gene-based analyses identified RAPGEF3 (P=1.18E-11) as significantly associated with WHRa in the all ancestry sex combined analyses after correction for multiple tests (P&lt;2.5E-6), though conditional analysis revealed that this result is driven by the top SV identified in this region. RAPGEF3 also shows a significant association (p=4.68E-12) in all ancestry, sex combined gene-based analysis of BMI. RAPGEF3 is expressed in subcutaneous and visceral adipose tissue, and has been implicated in insulin regulation. RAPGEF3 plays a role in the GLP1 pathway, which controls insulin secretion in response to blood glucose concentration. Our results highlight the importance of large-scale genomic studies for identifying LFV and RV influencing central fat distribution. Understanding these genetic effects may provide insights into the progression of central adiposity and highlight potential population-specific variants that increase susceptibility.
Interim Safety Data in a Prospective, Open-label, Multi-center Study of the Efficacy, Safety, Tolerability, and Pharmacokinetics of Plasmacap Ig in Patients with Primary Immunodeficiency Diseases (Pidd)
Authors: Richard L. Wasserman, Jacinthe Guindon, Jen Seda
Journal: Journal of Allergy and Clinical Immunology (2019)
Extending Antenatal Pertussis Immunization to Second Trimester or At-Birth Pertussis Immunization of Premature Infants?
Authors: Bahaa Abu-Raya, Michelle L. Giles
Journal: JAMA Pediatrics (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 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
Abstract 20574: Osteopontin Mediates Adhesion, Migration and Proliferation of Cardiac Progenitor Cells Through the Chemokine Receptor CXCR4
Authors: Philippe Bouaziz, Avishag Emanuelov, Suzan Salman, Jussi Leinonen, Chaim Lotan, Ronen Beeri
Journal: Circulation (2017)

Cell based cardiac repair offers an innovative strategy to repair the heart and all its damaged components. Achieving targeted trafficking of resident stem cell is critical for effective cardiac repair. More recent approaches have focused on taking lessons from molecular programming of cardiac progenitors (CPC) that build the developing heart. During vertebrate development, the heart is the first organ to function and cardiac progenitors are among the first cell lineages to be established from the mesoderm. However, migrations of cardiac progenitors have never been directly observed and the factor(s) controlling their movement are still unknown. We previously described niches of different CPCs in the left atrial appendage (LAA). Objectives and Methods: We aimed to characterize the LAA CPCs migration factors signatures using their genetic blueprint by gene array combined with both protein Orbitrape MS/MS analysis Osteopontin (OPN) is the most abundant factor related to migratory pathways in CPC lineages(by...
Racial disparities in the receipt of adjuvant chemotherapy in patients with resected stage I-III pancreatic adenocarcinoma.
Authors: Nina Niu Sanford, Xiaohan Xu, David J. Sher
Journal: Journal of Clinical Oncology (2019)

357 Background: Adjuvant chemotherapy for resected pancreatic adenocarcinoma is a category 1 NCCN recommendation, however studies have shown that many patients do not go on to receive chemotherapy after definitive surgery. Whether racial disparities exist for receipt of adjuvant chemotherapy is unknown. Methods: The National Cancer Database was used to identify 28,255 patients with non-metastatic pancreatic adenocarcinoma who underwent definitive surgery between 2005-2014. Multivariable logistic regression defined adjusted odds ratio (AOR) and 95% confidence intervals (CI) of receipt of adjuvant chemotherapy by race. Additional variables included in the model were age, sex, stage, node positivity, comorbidity index, facility type and insurance. Among those receiving chemotherapy, multivariable logistic regression assessed odds of treatment with multiagent chemotherapy and among those not receiving chemotherapy, predictors of chemotherapy refusal were assessed. Results: Compared to white patients, black patients were less likely to receive adjuvant chemotherapy (AOR 0.74, 95% CI 0.64-0.85, p &lt; 0.001) and multiagent adjuvant chemotherapy (AOR 0.80, 95% CI 0.72-0.88, p &lt; 0.001). The disparities were limited to patients with comorbidity score of 0 and persisted when analyses were restricted to only academic cancer centers. Among 2,405 patients not treated with chemotherapy, black patients had lower odds of refusing chemotherapy (AOR 0.72, 95% CI 0.55-0.93, p = 0.01). Conclusions: In this nationally representative study, black patients were less likely to receive NCCN-guideline concordant treatment for resected pancreatic adenocarcinoma; this disparity did not appear to be driven by increased refusal of treatment by black patients. Given that differences in quality of care may contribute to disparities in cancer survival, our findings suggest that outcomes for black patients could be improved by increasing the proportion receiving guideline-concordant adjuvant chemotherapy. Further investigation is needed to identify factors leading to the observed differences in this study, such that appropriate interventions can be undertaken to mitigate this disparity.
Abstract 18551: Impact of Potassium on Survival in Chronic Heart Failure Patients
Authors: Mette Aldahl, Anne-Sofie C Jensen, Line Davidsen, Matilde A Eriksen, Steen M Hansen, Berit J Nielsen, Maria L Krogager, Lars Køber, Christian Torp-Pedersen, Peter Søgaard
Journal: Circulation (2016)

Introduction: Diuretic therapy is frequently prescribed to patients suffering from chronic heart failure and carries an increased risk of impaired serum potassium homeostasis. Furthermore, chronic ...
Hypersensitivity reactions to antituberculosis drugs confirmed by interferon gamma enzyme-linked Immunospot assay
Authors: Amornrat Prasertcharoensuk, Yuda Chongpison, Pattarawat Thantiworasit, Nithikan Suthumcha, Supranee Buranapraditkun, Pawinee Rerknimitr, Hiroshi Chantaphakul, Jettanong Klaewsongkram
Journal: Journal of Allergy and Clinical Immunology (2019)
Safety and Efficiency of the YEARS Diagnostic Algorithm for Pregnant Patients with Clinically Suspected Acute Pulmonary Embolism —the Artemis Study
Authors: Liselotte M. Van Der Pol, Cecile Tromeur, Ingrid Bistervels, Thomas van Bemmel, Francis Couturaud, Laura M. Faber, Albert T.A. Mairuhu, Saskia Middeldorp, Marije ten Wolde, Erik A Klok, Menno V. Huisman
Journal: Blood (2018)
A randomized phase II study comparing oral S-1 plus 24-hour infusion of irinotecan (Iri) and bevacizumab (Bev) with FOLFIRI plus bevacizumab in patients with metastatic colorectal cancer (MCRC).
Authors: Sotaro Sadahiro, Toshiyuki Suzuki, Akira Tanaka, Kazutake Okada, Gota Saito, Hiroshi Miyakita, Takashi Ogimi, Lin Fung Chan
Journal: Journal of Clinical Oncology (2019)

613 Background: FOLFOX or FOLFIRI plus Bev is a first-line treatment for MCRC. Recent studies have confirmed that oral S-1 combined with Iri and Bev is equivalent to FOLFIRI plus Bev. Iri is usually administered as a short-term 90-min. infusion. However, the cytocidal activity is S-phase specific, and carboxylesterases, that convert Iri into SN-38, are less likely to become saturated when Iri is given as a long-term infusion. Therefore, a low dose of Iri given as a long-term infusion is expected to enhance antitumor activity. We conducted a randomized phase II study to compare this regimen with FOLFIRI plus Bev. Methods: The subjects comprised 120 chemotherapy-naïve patients with MCRC. The study group received 24-hr infusion of Iri at a dose of 125 mg/m 2 on days 1 and 15, combined with oral S-1 80 mg/m 2 on days 1 to 14. The FOLFIRI group received Iri at a dose of 150 mg/m 2 , 5-FU given at a dose of 400 mg/m 2 as a bolus injection and at a dose of 2400 mg/m 2 as a 46 hr-infusion, 200 mg/m 2 of leucovorin on days 1 and 15. Bev was given at a dose of 5.0 mg/kg on days 1 and 15 in both groups. Treatment was repeated every 4 weeks. The primary endpoint was the 1 y progression-free survival (PFS). Secondary endpoints were PFS, response rates (RR), overall survival (OS), and adverse events (AEs). Results: From October 2013 through December 2017, a total of 61 patients assigned to receive IRIS plus Bev (the A group) and 59 patients assigned to receive FOLFIRI plus Bev (the B group) were included in the analysis. The 1y RFS was 37.3% in the A group and 17.0% in the B group (p = 0.0281). The PFS was 10.2 mon in the A group and 10.0 mon in the B group, and the median OS was 27.0 mon and 28.6 mon, respectively (p = 0.26, p = 0.68). RR was significantly higher in the A group (87.0%) than in the B group (61.7%) (p = 0.005). The main grade 3 or 4 AEs were neutropenia (27.8%) and diarrhea (11.1%) in the A group and neutropenia (23.4%) and leukopenia (6.4%) in the B group. Conclusions: Our results showed that Iri, given biweekly as a 24-hour infusion in combination with oral S-1 and Bev, is a highly effective and well-tolerated regimen for the first-line treatment of MCRC. Clinical trial information: UMIN000014664.
Septal dysembryoplastic neuroepithelial tumor: a comprehensive clinical, imaging, histopathologic, and molecular analysis
Authors: Jason C H Chiang, Julie H Harreld, Ryuma Tanaka, Xiaoyu Li, Ji Wen, Chenran Zhang, Daniel R Boué, Tracy M Rauch, J Todd Boyd, Jie Chen, Joseph C Corbo, Thomas W Bouldin, Scott W Elton, Le-Wen L Liu, Deborah Schofield, Sunhee C Lee, John-Paul Bouffard, Maria-Magdalena Georgescu, Rimal H Dossani, Maria A Aguiar, Richard A Sances, Ali G Saad, Frederick A Boop, Ibrahim Qaddoumi, David W Ellison
Journal: Neuro-Oncology (2019)

Dysembryoplastic neuroepithelial tumors (DNETs) are uncommon neural tumors presenting most often in children and young adults and associated with intractable seizures. Rare midline neoplasms with similar histological features to those found in DNETs have been described near the septum pellucidum and termed "DNET-like neoplasms of the septum pellucidum." Due to their rarity, these tumors have been described in just a few reports and their genetic alterations sought only in small series. We collected 20 of these tumors for a comprehensive study of their clinical, radiological, and pathological features. RNA sequencing or targeted DNA sequencing was undertaken on 18 tumors, and genome-wide DNA methylation profiling was possible with 11 tumors. Published cases (n = 22) were also reviewed for comparative purposes. The commonest presenting symptoms and signs were related to raised intracranial pressure; 40% of cases required cerebrospinal fluid diversion. Epilepsy was seen in approximately one third of cases. All patients had an indolent disease course, despite metastasis within the neuraxis in a few cases. Radiologically, the septum verum/septal nuclei were involved in all cases and are the proposed site of origin for septal DNET (sDNET). Septal DNET showed a high frequency (~80%) of mutations of platelet derived growth factor receptor A (PDGFRA), and alterations in fibroblast growth factor receptor 1 (FGFR1) and neurofibromatosis type 1 (NF1) were also identified. In a genomic DNA methylation analysis alongside other neural tumors, sDNETs formed a separate molecular group. Genetic alterations that are different from those of cerebral DNETs and a distinct methylome profile support the proposal that sDNET is a distinct disease entity.
Hormone replacement therapy: changes in prescribing practice
Authors: Melanie Davies, Haitham Hamoda
Journal: BMJ (2019)

Vinogradova and colleagues’ study is a welcome addition to the literature on the association between hormone replacement therapy (HRT) and risk of venous thromboembolism.1 The results are broadly in keeping with other research in this area, but this study provides greater detail about the potential risks of different HRT preparations, including the different types of oestrogen and progestogens, …
Aspirin and statin use and the risk of gallbladder cancer.
Authors: Kritika Prasai, Mohamed Mady, Siddhartha Yadav, Mohamed Abdelrahim Muddathir Hassan, Lewis R. Roberts, Amit Mahipal
Journal: Journal of Clinical Oncology (2019)

243 Background: The risk factors for gallbladder cancer (GBC) are poorly understood and preventive therapeutic options have not been identified. The use of aspirin (ASA) and/or statin has been associated with reduced risk of several gastrointestinal cancers. In this study, we explore if the use of ASA or statin is associated with a reduced risk of GBC. Methods: We identified patients with GBC diagnosed between the years 2000 and 2016 at Mayo Clinic. We identified matched controls in 2:1 fashion for age, gender and country of residence from patients who underwent cholecystectomy at Mayo Clinic. We collected information on co-morbidities and use of statins or ASA by retrospective chart review. We compared baseline characteristics between cases and controls using Fisher’s exact test for categorical variables and Mann-Whitney U test for continuous variables. We used binomial logistic regression to calculate the odds ratio (OR) and 95% confidence intervals (CI) to estimate the association of ASA or statin use with GBC. The logistic regression model included history of cholelithiasis, diabetes, hypercholesterolemia (HCL), hypertension (HTN), hyperthyroidism, hypothyroidism, primary sclerosing cholangitis (PSC), inflammatory bowel disease (IBD), cirrhosis and statin or ASA use as covariates. Results: 633 cases and 1,266 controls were included in our final analysis. The median age at diagnosis of cases and controls was 67 years. The control group had a significantly (p &lt; 0.05) higher proportion of patients with cholelithiasis, HCL, HTN, hypothyroidism and liver cirrhosis compared to the cases. The case group,contrarily, had a significantly higher proportion of patients with PSC and IBD. In univariate analysis, ASA (OR: 0.41; 95% CI: 0.33-0.52) or statin (OR: 0.48; 95% CI: 0.38-0.60) use was associated with a lower risk of GBC (p &lt; 0.001). However, in multivariate analysis, ASA use was associated with a lower risk of GBC (OR: 0.52; 95% CI: 0.41-0.67, p &lt; 0.001) whereas statin use was not (OR: 0.76; 95% CI: 0.56-1.03, p = 0.08). Conclusions: Our study demonstrates that aspirin use is associated with a reduced risk of GBC, whereas statin use is not. Further studies on GBC are needed to confirm these results and to elucidate mechanisms that explain the risk reduction with aspirin.
A multivariate model to define risk groups among patients with curatively resected stage I and II colon carcinoma: Final report of a retrospective cohort study.
Authors: Luis F. Onate-Ocana
Journal: Journal of Clinical Oncology (2019)

696 Background: Patients with stage I or II colon carcinoma (CC) have a 10 or 20% risk, respectively, of presenting recurrent disease after a potentially curative surgical resection and adjuvant chemotherapy have not improved survival in this setting. In this study, we present a multivariate model to define risk groups. Methods: Consecutive cases with stage I and II CC treated at a single cancer center in Mexico City, from January 1992 to December 2016, were included in this 25-year cohort. Clinical history and biochemical data were registered, and colon resection was performed with curative intention with standard lymphadenectomy. Standard hematoxylin-eosin slides and CDX2 immunohistochemistry (IHC) slides were analyzed by two independent pathologists. The Kaplan-Meier method and Cox model were used to analyze the association of prognostic factors and overall survival (OS). Results: 3,301 cases of colorectal cancer were treated during this study, but only 556 patients with stage I and II CC were included in the database: 266 women (47.8%) and 290 males (52.2%) (mean age 57.9 years); 52 (9.4%), 431 (77.5%), 36 (6.5%) and 37 (6.7%) were pTNM stages I, IIa, IIb, and IIc, respectively. R0 resection was performed in 548 patients (98.6) and R1 in 8 (1.4%). Location in the left colon (HR 1.63), hemoglobin (HR 0.93), serum albumin (HR 2.45), prognostic nutritional index 0.915), platelet count (HR 0.998), body mass index (HR 0.94), basal carcinoembryonic antigen (HR 1.0), TNM stage [stage I reference category, IIa (HR 5.46), IIb (HR 4.42), IIc (HR 9.28)], R1 residual disease (HR 2.8), negative CDX2 IHC (HR 2.1), and use of adjuvant chemotherapy (HR 0.629) were included in the final model as independent predictors of OS (model p &lt; 0.0001).Predicted survival functions using this model defined three distinct risk groups. Conclusions: This multivariate model adds significant prognostic value to the pTNM classification. This model can be useful for stratifying prognosis in patients with CC and will aid in the design of randomized clinical trials evaluating the usefulness of adjuvant chemotherapy in this subgroup of patients with CC.
Response to ‘IgA vasculitis in adults: few certainties and many uncertainties’ by Hočevar <i>et al</i>
Authors: Alexander Tracy, Anuradhaa Subramanian, Nicola J Adderley, Lorraine Harper, Krishnarajah Nirantharakumar
Journal: Annals of the Rheumatic Diseases (2019)

We thank Hocevar and colleagues for their comments on our recently published work on the epidemiology of IgA vasculitis (IgAV) in adults and children.1 2 We agree that there is some uncertainty regarding the incidence of adult-onset IgAV as this has not previously been widely studied.

Our calculated incidence of 2.20 (95% CI 2.08 to 2.37) per 100 000 person-years in adults is slightly higher than most previous work has suggested, but is lower than that reported by Hocevar et al in a Slovenian tertiary centre study with no clearly demarcated denominator population.2–4 This disparity may be related to interpopulation differences, for example, in exposure to environmental risk factors such as viral infections.5 Alternatively, the difference may be due to contrasting strategies used to identify cases of IgAV. Hocevar and colleagues used both clinical and …
Dexamethasone—Friend or Foe for Patients With Glioblastoma?
Authors: Eric T. Wong, Kenneth D. Swanson
Journal: JAMA Neurology (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 Neurology 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 Neurology journal
A multi-omics evaluation of the non-lesional skin surface identifies atopic dermatitis with food allergy (AD FA+) as a unique endotype
Authors: Donald Y.M. Leung, Agustin Calatroni, Livia S. Zaramela, Nathan T. Dyjack, Kanwaljit K. Brar, Petra LeBeau, Gloria L. David, Keli Johnson, Susan B. Leung, Simion Kreimer, C. Conover Talbot, Robert N. Cole, Marco A. Ramirez-Gama, Bo Liang, Cydney Rios, Michael T. Montgomery, John Jung, Irina Bronova, Max A. Seibold, Karsten Zengler, Evgeny Berdyshev, Elena Goleva
Journal: Journal of Allergy and Clinical Immunology (2019)
Inflammation-induced glycolytic switch controls suppressivity of mesenchymal stem cells via STAT1 glycosylation
Authors: R. Jitschin, M. Böttcher, D. Saul, S. Lukassen, H. Bruns, R. Loschinski, A. B. Ekici, A. Reis, A. Mackensen, D. Mougiakakos
Journal: Leukemia (2019)