tbuckley/cabot-search huggingface dataset:
Assessment of methylated BCAT1 and IKZF1 circulating tumor DNA as a potential diagnostic and prognostic biomarker in esophagogastic cancers.
Authors: Mei Mei Chan, Jean M. Winter, Susanne Kartin Pedersen, Amitesh Chandra Roy, David I. Watson, Damian Hussey, Graeme P. Young, Erin L. Symonds
Journal: Journal of Clinical Oncology (2022)

348 Background: Esophagogastric cancers (EG cancers) are associated with high mortality and poor treatment outcomes due to advanced disease at diagnosis. Reliable non-invasive biomarkers are lacking for detection and prognostication. The aim of this study was to assess the clinical utility of methylated BCAT1 and IKZF1 circulating tumour DNA (ctDNA) for detection and prognosis of EG cancers. Methods: Blood samples were collected from patients diagnosed with either esophageal or gastric adenocarcinoma prior to commencing any treatment. DNA was extracted from plasma and analysed for methylation of BCAT1 and IKZF1, and ACTB as the reference gene, by multiplex qPCR. ctDNA positivity rates were assessed against cancer clinicopathological features using chi-squared tests and age-adjusted logistic regression with odds ratios (OR). Secondary outcome was overall survival after 12 months using cox-proportional hazard ratio (HR). Results: Ninety-seven patients (77/97 (79%) male; 70 (72%) with esophageal cancer and 27 (28%) with gastric cancer) were enrolled with median age 72 years (IQR = 61-79). Fifty-three (55%) were ctDNA positive. There was no difference between the ctDNA positivity rate of esophageal and gastric cancers (p &gt; 0.05). Positivity was significantly associated with node positive tumours (N0 = 6/23 (20.7%), N1 = 5/10 (50%), N2 = 11/17 (64.7%), N3 = 3/4 (75%); p = 0.01) and depth of invasion (T1 = 0/9 (0%), T2 = 5/12 (41.7%), T3 = 17/36 (47.2%), T4 = 5/6 (83.3%), p = 0.049). ctDNA positivity was independent of history of GORD or Barrett’s disease (p &gt; 0.05). There was a significant association between ctDNA and advanced stage disease (Stage I = 1/13 (7.7%), Stage II = 2/12 (16.7%), Stage III = 25/40 (62.5%), Stage IV = 25/32 (78.1%)), with stage IV cases having a 43-fold increased odds for a positive ctDNA result compared to stage I (OR = 43.1, 95%CI 4.7-392.0; p = 0.001). Patients testing positive for ctDNA had poorer overall survival outcomes compared to those testing negative (HR 4.23, 95% CI 1.84-9.68, p &lt; 0.001). Conclusions: Our study demonstrates a potential role for methylated BCAT1 and IKZF1 ctDNA as a biomarker for the detection of EG cancers. The detection of ctDNA is significantly associated with poorer survival outcomes, with further studies warranted to determine whether ctDNA can be an independent predictor of survival. The integration of this ctDNA assay into clinical practice could further improve risk stratification, which may guide treatment strategies.
News &amp; Notes
Journal: Journal of Allergy and Clinical Immunology (2020)

The decision to cancel the 2020 AAAAI Annual Meeting was a difficult one, but it was also ultimately the right one.Many people were looking forward to this year's event, and we've been hard at work putting together a virtual option that highlights some of the amazing work done by our speakers and researchers this year.While we understand it isn't quite the same as attending a live event, we hope this year's Virtual Annual Meeting sparks thought, discussion, and practice changes just as our live event does every year.Here is a guide to help you easily navigate our 2020 Virtual Annual Meeting and find the education you're most interested in.
KRAS mutation methylation clonality in early-stage pancreatic cancer.
Authors: Jeanne Kowalski, Qi Xu, Hsueh Ping Chao, Heta Gandhi, Kyaw Lwin Aung, William H. Matsui
Journal: Journal of Clinical Oncology (2022)

614 Background: KRAS is mutated in 90% of pancreatic cancers making it a seemingly ideal target for treatment and yet, with the exception of the rare G12C mutation, KRAS is undruggable for the vast majority of pancreatic patients. Herein, we characterize, in silico, KRAS methylation-derived mutation clonal and subclonal diversity in PDAC and examine their impact upon clinical outcomes. Methods: We developed a mutation methylation (MM) clonality workflow for gene mutation assignment as clonal versus subclonal and applied it genome-wide to TCGA data. For comparison, we used the cancer cell fraction (CCF) clonality prediction. We examined clinical outcomes by comparing in months (mos), Kaplan-Meier estimated overall survival (OS) using a log-rank test and a cox model for testing several features. We performed differential gene expression, differential gene correlation, and gene set enrichment analyses (GSEA) between KRAS MM clonal versus subclonal early stage pancreatic patients. Results: Using 104 TCGA early stage pancreatic cancer patient tumors from TCGA with mutation, methylation and clinical outcomes data, we defined KRAS MM clonality (n = 70 clonal, n = 34 subclonal) and CCF clonality (n = 74 clonal, n = 28 subclonal) tumors. Clonality assignment between methods was 53% clonal and 17% subclonal concordant, and 19% discordant among samples. KRAS MM clonality was associated with significantly (p = 0.046) shorter OS (median OS = 11.5 mos) as compared to the KRAS subclonal group (median OS = 15 mos). By comparison, KRAS CCF clonal and subclonal patient groups did not differ in their OS. When RNA-Seq derived subtypes for pancreatic cancer were included in a model with our KRAS MM clonality marker, only our marker remained as significantly associated with OS. Median KRAS gene expression was significantly (p = 0.01) higher in the KRAS MM clonal versus subclonal group. A GSEA showed enrichment of MYC targets in the KRAS clonal group. We identified 72, mostly protein coding genes residing on chromosomes 5q, 7p and 8p that correlated with KRAS gene expression only in the subclonal group. Conclusions: Our analyses shows a potential clonality dissection of the established 90% KRAS mutation rate in pancreatic cancer, which based on our MM workflow, may be dissected into 61% KRAS clonal and 30% KRAS subclonal. By assigning clonality based on another DNA data type using CCF, we obtain 65% KRAS clonal and 25% KRAS subclonal. Thus, regardless of which DNA-based workflow, overall, the KRAS clonality rates are similar. There is a notable difference however in patient-level assignment of KRAS clonality as only our workflow showed poor OS associated with KRAS clonality. The introduction of a methylation-based mutation clonality marker could prove invaluable when used in combination with methylation-based circulating tumor DNA assays for patient and treatment selection, and clinical trial monitoring of tumor responses.
Weight-for-Height, Body Fat, and Development in Children in the East Asia and Pacific Region
Authors: Fanny Petermann-Rocha, Nirmala Rao, Jill P. Pell, Carlos Celis-Morales, Ian C. K. Wong, Frederick K. Ho, Patrick Ip
Journal: JAMA Network Open (2022)

Weight-for-height z score (WHZ) is a standard indicator of children's nutritional status even though it does not fully reflect body fat.To examine the combined association of WHZ and body fat with early development in the East Asia and Pacific region.Children from the East Asia-Pacific Early Child Development Scales validation study, with full data available regarding their nutritional status and outcomes, were included in this cross-sectional analysis. In brief, a multilevel stratified random sampling was used to select representative samples from each participating country in the study. WHZ and body fat were independently trichotomized using established references and were combined to form a 9-category exposure variable. Data collection was performed between 2012 and 2014, and the analyses were conducted in June 2021.The binary outcome variable of not being developmentally on track (hereafter referred to as poor development) was defined as a score less than the 25th percentile in the following domains: cognitive, language, socioemotional, motor development, and total development score. Poisson regression models were used to analyze the associations between the combined categories and poor development, adjusted for sociodemographic factors.A total of 6815 children (mean [SD] age, 4.02 [0.8] years; 3434 girls [50.4%]) had full data available and were included in this study. Compared with children with normal weight and normal fat, those with wasting and low body fat had the highest likelihood of total poor development (prevalence ratio, 1.47; 95% CI, 1.28-1.70), followed by those with normal weight but low fat (prevalence ratio, 1.23; 95% CI, 1.11-1.36). Similar associations were found in language, cognitive, and socioemotional development, but not in motor development.Poor development was more commonly found in children with low body fat independent of WHZ (wasted or normal weight). Early public health strategies may consider using a combination of WHZ and body fat as an indicator of poor development.
Abstract P238: Cardiovascular Risk Factors for Intimal and Medial Calcification in a High-risk Population
Authors: Eva Hendriks, Sabine Zwakenberg, Pim de Jong, Jan Westerink, Gert Jan de Borst, Maarten Jan Cramer, Yvonne van der Schouw, Joline Beulens
Journal: Circulation (2017)

Introduction: Arterial calcification is associated with an increased cardiovascular risk. Intimal calcification has long been held responsible for this association, whereas the role of medial calcification was unclear. Hypothesis: We hypothesize that the risk factor profile in patients with high cardiovascular risk differs for those with intimal or medial calcification of the lower extremity arteries. Methods: We conducted a cross-sectional study of 203 patients included in the Second Manifestations of ARTerial Disease (SMART) study, comprising of patients with CVD as well as patients at high risk for CVD, who underwent CT (computed tomography) scanning of the lower extremities. Calcification in the femoral and crural arteries was scored as absent, dominant intimal, dominant medial or indistinguishable according to a previously validated algorithm scoring linearity and circularity. We fitted multinomial regression models assessing the associations of cardiovascular risk factors with different patterns of calcification. Results: No calcification was present in 18% for the femoral and 28% for the crural arteries, while prevalence of intimal calcification was 44% and 38%. Medial calcification prevalences were 25% and 20% for the femoral and crural arteries, respectively. We found considerable consistency in the predominant calcification pattern of the crural and femoral arteries (linear weighted Cohen’s kappa [0.41, 95%CI 0.29-0.52]). Patients with dominant medial calcification were older, more often male and more often had diabetes than patients with intimal calcification. Conversely, patients with intimal calcification were more often smokers than patients with medial calcification. In multinomial logistic regression models, age was a significant risk factor for all types of calcification compared with no calcification. Male sex was associated with an increased risk of medial calcification [OR femoral 10.37, 95%CI 2.14-50.32], but not with intimal or indistinguishable calcification, compared with no calcification. Current smoking was associated with intimal calcification[OR femoral 3.25, 95%CI 0.98;10.83], but not with medial calcification. No significant relationships were found with other cardiovascular risk factors. Conclusions: Within the same individual, a predominant arterial calcification type (intimal or medial) often exists throughout the lower extremity. These patterns of calcification appear to have different associated risk factor profiles.
Disparities by Sex and Race and Ethnicity in Death Rates Due to Opioid Overdose Among Adults 55 Years or Older, 1999 to 2019
Authors: Maryann Mason, Rebekah Soliman, Howard S. Kim, Lori Ann Post
Journal: JAMA Network Open (2022)

<h3>Importance</h3> Rates of opioid overdose deaths are increasing for older adults. Less is known about these deaths compared with those of younger adults. <h3>Objective</h3> To analyze rate variation among opioid overdose deaths in older adults by sex and by race and ethnicity over time. <h3>Design, Setting, and Participants</h3> This 21-year longitudinal cross-sectional study of adults who died due to opioid overdose at 55 years or older stratified by sex and by race and ethnicity used data from the Multiple Cause of Death database from the Centers for Disease Control and Prevention Wide-Ranging Online Data for Epidemiologic Research. The data include all opioid overdose deaths among this age group that occurred between January 1, 1999, and December 31, 2019 (N = 79 893). <h3>Exposures</h3> Sex and racial and ethnic groups. <h3>Main Outcomes and Measures</h3> Rates of opioid overdose deaths per 100 000 population by sex and by race and ethnicity for persons 55 years or older. <h3>Results</h3> During the period 1999 to 2019, 79 893 US residents 55 years or older died due to an opioid overdose. Among these individuals, 79.97% were aged 55 to 64 years, and 58.98% were men. Annual numbers of deaths increased over time from 518 in 1999 to 10 292 in 2019. Annual rates of opioid overdose deaths per 100 000 persons 55 years or older increased over time and ranged from 0.90 in 1999 to 10.70 in 2019. Substantial variation by sex and by race and ethnicity was found. In 2013, rates among non-Hispanic Black men began to diverge from those of other demographic subgroups. By 2019, the opioid overdose fatality rate among non-Hispanic Black men 55 years or older was 40.03 per 100 000 population, 4 times greater than the overall opioid overdose fatality rate of 10.70 per 100 000 for persons of the same age. <h3>Conclusions and Relevance</h3> In this longitudinal cross-sectional study of US adults who died due to opioid overdose, the burden of opioid overdose deaths among older adults since 2013 was most concentrated among non-Hispanic Black men. Deaths among non-Hispanic Black men were disproportionality represented in the overall increase in the rate of opioid overdose deaths among older adults. Further research is needed to inform policy and practice.
Consensus Conferences
Authors: Don Riesenberg
Journal: JAMA (1987)

Two articles in this issue ofTHE JOURNALpertain to the National Institutes of Health Consensus Development Program. One is the Consensus Conference statement on the management of clinically localized prostate cancer.<sup>1</sup>The other is an investigation by Kosecoff and colleagues<sup>2</sup>into the effect of Consensus Conference recommendations on how physicians practice. The former summarizes clinical and histological grading of, and surgical and radiation therapy for, a common malignancy. The latter suggests that the former will make little difference. Kosecoff et al<sup>2</sup>reviewed charts from ten Washington State hospitals before and after four Consensus Conferences, two on various aspects of breast cancer and one each on coronary artery bypass surgery and cesarean childbirth. Although there was a trend across time toward greater "compliance" with consensus-panel recommendations, that trend peaked<i>prior</i>to the conferences. And compliance with six of 11 recommendations remained at less than 50% two years
Estudos cirurgicos
Journal: JAMA (1941)

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
Implementation of INHERET, an Online Family History and Cancer Risk Interpretation Program for Primary Care and Specialty Clinics
Authors: Lynn A. McCain, Kara J. Milliron, Amanda M. Cook, Robert Paquette, Jasmine B. Parvaz, Susan D. Ernst, Anne L. Kittendorf, Diane M. Harper, Phillip Zazove, Jim Arthurs, Jerry A. Tippie, Bailey Hulswit, Lee F. Schroeder, David F. Keren, Sofia D. Merajver
Journal: Journal of the National Comprehensive Cancer Network (2022)

Background: Individuals at increased risk for cancer are ascertained at low rates of 1% to 12% in primary care (PC). Underserved populations experience disparities of ascertainment, but data are lacking. INHERET is an online personal and family history tool to facilitate the identification of individuals who are eligible, according to guidelines, to be counseled on germline genetic testing and risk management. Patients and Methods: INHERET data entry uses cancer genetics clinic questionnaires and algorithms that process patient data through NCCN Clinical Practice Guidelines in Oncology and best practice guidelines. The tool was tested in silico on simulated and retrospective patients and prospectively in a pilot implementation trial. Patients in cancer genetics and in PC clinics were invited to participate via email or a card. Informed consent was completed online. Results: INHERET aimed to integrate patient data by algorithms based on professional and best practice guidelines to elicit succinct, actionable recommendations that providers can use without affecting clinic workflow or encounter length. INHERET requires a 4th-grade reading level, has simple navigation, and produces data lists and pedigree graphs. Prospective implementation testing revealed understandability of 90% to 100%, ease of use of 85%, and completion rates of 85% to 100%. Physicians using INHERET reported no added time to their encounters when patients were identified for counseling. In a specialty genetics clinic, INHERET’s data were input, on average, within 72 hours compared with 4 to 6 weeks through standard care, and the queue for scheduling patients decreased from 400 to fewer than 15 in &lt;6 months. Conclusions: INHERET was found to be accessible for all education and age levels, except patients aged &gt;70 years, who encountered more technical difficulties. INHERET aided providers in conveying high-risk status to patients and eliciting appropriate referrals, and, in a specialty clinic, it produced improved workflows and shortened queues.
<i>ERJ</i>Podcast October 2017: Lessons from IPF clinical trials over the past 25 years
Journal: European Respiratory Journal (2017)

As part of the October issue, the European Respiratory Journal presents the latest in its series of podcasts. Chief editor Marc Humbert discusses the lessons learned from clinical trials in idiopathic pulmonary fibrosis over the past 25 years with Prof. Ganesh Raghu from the University of Washington, Seattle, WA, USA.
Developing a Flexible National Wastewater Surveillance System for COVID-19 and Beyond
Authors: Aparna Keshaviah, Xindi C. Hu, Marisa Henry
Journal: Environmental Health Perspectives (2021)

Wastewater testing offers a cost-effective strategy for measuring population disease prevalence and health behaviors. For COVID-19, wastewater surveillance addresses testing gaps and provides an early warning for outbreaks. As U.S. federal agencies build a National Wastewater Surveillance System around the pandemic, thinking through ways to develop flexible frameworks for wastewater sampling, testing, and reporting can avoid unnecessary system overhauls for future infectious disease, chronic disease, and drug epidemics.
Final Results of a Phase 2 Study of Bendamustine in Combination with Dexamethasone in Patients with Previously Treated Systemic Light-Chain (AL) Amyloidosis
Authors: Galina Grigoriev Lagos, Suzanne Lentzsch, Raymond L. Comenzo, Jeffrey Zonder, Keren Osman, Julia Gould, Wei-Yann Tsai, Silva Pregja, Mariamne Reyna, Shahzad Raza, Vaishali Sanchorawala, Heather Landau
Journal: Blood (2016)
BOOK REVIEWS
Authors: B. LEYLAND-JONES
Journal: JNCI Journal of the National Cancer Institute (1989)

BOOK REVIEWS Cancer Growth and Progression. Hans E. Kaiser. Dordrecht, The Netherlands: Kluwer Academic Publishers, 1989. Volume 1: Fundamental Aspects of Cancer. Ronald H. Goldfarb, ed. 211 pp. $99.50. Volume 2: Mechanisms of Carcinogenesis. Elizabeth K. Weisburger, ed. 199 pp. $9.50. Volume 3: Influence of Tumor Development on the Host. Lance A. Liotta, ed. 240 pp. $99.50. Volume 4: Influence of the Host on Tumor Development. Ronald B. Herberman, ed. 191 pp. $99.50. Volume 5: Comparative Aspects of Tumor Development. Hans E. Kaiser, ed. 259 pp. $99.50. BRIAN LEYLAND-JONES BRIAN LEYLAND-JONES Investigational Drug Branch, CTEP, National Cancer InstituteExecutive Plaza North, Rm. 731-B Bethesda, MD 20852 Search for other works by this author on: Oxford Academic PubMed Google Scholar JNCI: Journal of the National Cancer Institute, Volume 81, Issue 17, 6 September 1989, Pages 1328–1329, https://doi.org/10.1093/jnci/81.17.1328 Published: 06 September 1989
Error in Author Affiliation
Authors: Elliott Norrish, Juan Kaski
Journal: JAMA Cardiology (2020)

Hongwei Ji, MD; Andy Kim, BA; Joseph E. Ebinger, MD; Teemu J. Niiranen, MD; Brian L. Claggett, PhD; C. Noel Bairey Merz, MD; Susan Cheng, MD, MPH, MMSc
Leads from the MMWR
Journal: JAMA (1987)

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
Elevated plasma level of asymmetric dimethylarginine (ADMA) is associated with atherosclerotic disease of the thoracic aorta Carol P. Cardinale, Ali Fard, Marc S. Eisenberg, Melissa A. Kazanowski, Marco R. DiTullio, Shunichi Homma. Columbia University, New York, NY
Journal: Journal of the American College of Cardiology (2001)