tbuckley/cabot-search huggingface dataset:
Abstract P330: Childhood Material Deprivation and Self-reported, Physician-diagnosed Myocardial Infarction in a Southern Cohort of Middle-aged African American Men and Women
Authors: Debbie S Barrington, Sherman A James
Journal: Circulation (2017)

Introduction: The antecedents of cardiovascular disease occur early in life. However, most studies reporting associations between childhood social conditions and adult myocardial infarction (MI) have been conducted on European and US white populations. Hypothesis: We hypothesized that adverse childhood social conditions would be associated with increased risk for MI in a Southern cohort of middle-aged African American men and women. Methods: Multiple logistic regression models were used to investigate sex-specific associations between childhood material deprivation and 13 year incidence of self-reported-physician diagnosed MI among 413 Black men and 754 Black women in the Pitt County (NC) Study. Cohort members were aged 25 to 50 years in 1988, the baseline year, and were re-interviewed in 2001. For this study, childhood was defined as birth to age 13 years; and childhood material deprivation was measured by a composite index of receipt of public assistance, food insecurity, and the lack of household heat, electricity, or plumbing. Odds ratios (OR) of the association between childhood material deprivation and adult MI were estimated after adjusting for both childhood and adulthood socioeconomic position, demographics, lifestyle, co-morbidities and psychosocial factors. For women, menopausal status was also controlled. Results: Men exposed to 1-2 types of childhood material deprivation had 38% lower odds of MI than men unexposed to such deprivation during childhood, OR = 0.62; 95%CI: (0.41, 0.92). However, men exposed to 3+ types of material deprivation during childhood were 3 times more likely to report a physician-diagnosed heart attack than men who were unexposed, OR = 3.07; 95%CI: (1.79, 5.29). No difference in 13 year MI risk was observed between women exposed to 1-2 types of childhood material deprivation and women who were unexposed, OR = 1.23; 95%CI: (0.70, 2.16). However, women exposed to 3+ types of early-life material deprivation were 5 times more likely to report a physician-diagnosed MI compared to women who were unexposed, OR = 5.20; 95%CI: (2.58, 10.48). Conclusions: Our findings suggest that early childhood is a sensitive period wherein severe socioeconomic disadvantage may trigger, or exacerbate, biological processes that increase risk of MI, by middle age, in African American men and women.
Outcomes of lenalidomide in diffuse large B-cell (DLBCL) and high-grade NHL (HGBCL): A single-center retrospective analysis.
Authors: Thomas David Rodgers, Andrea M Baran, Patrick Michael Reagan, Carla Casulo, Andrew Evans, Walter Richard Burack, Jonathan W. Friedberg, Paul M. Barr
Journal: Journal of Clinical Oncology (2019)

7547 Background: Outcomes remain poor for patients with relapsed refractory DLBCL and HGBCL, especially those ineligible for a stem cell transplant or CAR T-cell therapy. Lenalidomide has efficacy in these groups, most notably in the activated B-cell like (ABC) subtype when defined by gene expression profiling. We analyzed the outcomes of consecutive patients with DLBCL treated with lenalidomide, focusing on characteristics such as transformed histology and MYC translocation status. Methods: We performed a retrospective review of consecutive patients with transformed indolent NHL, DLBCL, and HGBCL treated with lenalidomide at the University of Rochester between 2011-2018. Cell of origin was determined by Hans algorithm and FISH was performed to detect MYC, BCL2, and BCL6 translocations. Kaplan Meier estimates and descriptive statistics were utilized for analysis. Results: 62 patients were identified with a median age of 76 years, the majority with &gt; 2 prior therapies. ORR was 43.5%, including 14 patients with a CR. Median PFS was 4.6 months with 18 patients achieving a PFS &gt; 1 year. Median OS was 14 months. No difference in PFS, OS, or ORR was observed between the de novo germinal center b-cell (GCB) and non-GCB populations (PFS 4 vs. 5 months, p = 0.87). 16 patients with transformed FL had a median PFS of 24 months and a median OS of 46.7 months (vs. de novo GCB OS of 7.8 months, p = 0.02). Notably, 6/7 MYC+ patients achieved an objective response, including 3 with a CR. All patients with double and triple hit disease had an objective response, including two PRs and one CR. Conclusions: Our experience confirms the clinical activity of lenalidomide in heavily pretreated older adults with DLBCL. Outcomes did not differ by cell of origin using the Hans immunohistochemistry algorithm and durable responses were observed, particularly in transformed FL. Nearly all of the MYC+ patients responded, including those with double/triple hit genetics, and almost half achieved a CR. Based on our data, lenalidomide may be an optimal bridge to consolidative cellular therapy in high-risk patients irrespective of genotype, particularly in transformed indolent histologies.
Abstract #1185: Loss of N-myc downstream-regulated gene 1 (NDRG1) increases prostate cancer cell invasion by upregulating CCL5
Authors: Lan Chun Tu, Xiaowei Yan, Biaoyang Lin, Lee Hood, Qiang Tian
Journal: Cancer Research (2009)

The N-myc downstream regulated gene 1 (NDRG1) is an androgen-induced gene that can suppress metastasis of prostate cancer. However, the mechanism for this suppression remains unknown. This study set out to elucidate the molecular events underlying NDRG1-regulated metastasis. We demonstrated that silencing NDRG1 by siRNA knock-down from androgen-treated LNCaP cells increased cell invasion through matrigel without affecting cell proliferation. Gene expression profiling of the androgen-treated cells after NDRG1 silencing identified CCL5 as a potential downstream target. We found that the secretion of CCL5 protein was significantly increased in response to NDRG1 knock-down, and that the CCL5-containing conditional medium stimulated cell invasion _ an effect that could be reversed in the presence of a specific blocking antibody_indicating that CCL5 is involved in cell invasion mediated by the loss of NDRG1. Furthermore, we showed that CCL5 stimulated protein tyrosine phosphorylation in both LNCaP and DU145 cells. Our findings, for the first time, link NDRG1 to CCL5 signaling and may lead to new strategies for interfering NDRG1-regulated cell invasion and provide important markers for evaluating prostate cancer prognosis.  Citation Information: In: Proc Am Assoc Cancer Res; 2009 Apr 18-22; Denver, CO. Philadelphia (PA): AACR; 2009. Abstract nr 1185.
Abstract 2701: Functionally specialized subsets of exhausted CD8+ T cells mediate tumor control and differentially respond to checkpoint blockade
Authors: Brian C. Miller, Debattama R. Sen, Rose Al Abosy, Kevin Bi, Yamini V. Virkud, Martin W. LaFleur, Kathleen B. Yates, Ana Lako, Kristen Felt, Girish S. Naik, Michael Manos, Evisa Gjini, F. Stephen Hodi, Scott J. Rodig, Arlene H. Sharpe, W. Nicholas Haining
Journal: Cancer Research (2019)

Abstract T cell dysfunction in the tumor microenvironment (TME) is a hallmark of many cancers. Reinvigoration of T cell function by PD-1 checkpoint blockade can result in striking clinical responses, but is only effective in a minority of patients. The basis for T cell dysfunction in the TME, as well as the mechanisms by which anti-PD-1 therapy acts on dysfunctional T cells are not fully understood. Here we show that anti-PD-1 therapy acts on a specific subpopulation of CD8+ tumor-infiltrating lymphocytes (TILs) in melanoma mouse models, which can also be found in patients with melanoma. We find that dysfunctional CD8+ TILs possess canonical epigenetic and transcriptional features of T cell exhaustion, mirroring those seen in chronic viral infection. Similar to chronic viral infection, exhausted CD8+ TILs contain a subpopulation of “progenitor exhausted” T cells that have a distinct regulatory state. Progenitor exhausted TILs also have critical functional attributes that are not shared by the majority “terminally exhausted” TILs: they retain more polyfunctionality, persist following transfer into tumor-bearing mice, and differentiate to repopulate terminally exhausted TILs in the TME. As a result, progenitor exhausted CD8+ TILs are better able to control tumor growth than terminally exhausted cells. Progenitor exhausted, but not terminally exhausted, CD8+ TILs can respond to anti-PD-1 therapy but this occurs without reversion of their exhausted epigenetic state. Human melanomas contain CD8+ T cells with a progenitor exhausted phenotype and patients with a higher fraction of this subpopulation in their tumors have a significantly longer duration of response to combination checkpoint blockade therapy. Therefore, approaches to expand progenitor exhausted CD8+ T cells in the tumor microenvironment may be an important component of improving checkpoint blockade response. Citation Format: Brian C. Miller, Debattama R. Sen, Rose Al Abosy, Kevin Bi, Yamini V. Virkud, Martin W. LaFleur, Kathleen B. Yates, Ana Lako, Kristen Felt, Girish S. Naik, Michael Manos, Evisa Gjini, F. Stephen Hodi, Scott J. Rodig, Arlene H. Sharpe, W. Nicholas Haining. Functionally specialized subsets of exhausted CD8+ T cells mediate tumor control and differentially respond to checkpoint blockade [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr 2701.
Childhood Maltreatment and Amygdala Threat Reactivity in Young Adults—Timing Is Everything
Authors: Gregory A. Fonzo
Journal: JAMA Psychiatry (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 Psychiatry 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 Psychiatry journal
Abstract 2172: Quantification of ERK activity in cancer cell lysates and tumor extract using differential sensing methods
Authors: Diana Zamora-Olivares, Tamer S. Kaoud, Lingyu Zeng, Mitchell Telles, Eric V. Anslyn, Kevin N. Dalby
Journal: Cancer Research (2019)

Abstract The activity of protein kinases in biological samples is typically estimated by determining the phosphorylation status of either the kinase itself, or a known cellular substrate. This is typically evaluated by multi-step western blotting, or proteomics procedures. Such procedures typically provide qualitative estimates of the modifications in question. While immunoblotting and proteomics procedures can be used in a quantitative manner, their complicated workflow diminishes reproducibility. Futhermore, modifications do not necessarily correlate closely with a protein kinase’s activity. The motivation for this work was to assess the potential of a peptide array to quantify ERK activity in cancer cell lines and tumor samples, without the need to suppress related kinase activities. This work shows that a library of cross-reactive peptide-based biosensors, along with chemometric analysis can be used to profile a kinase activity in cancer cell lines. Significantly, the array is suitable for quantifying unknown levels of ERK activity in unfractionated cancer cell lysates and tumor samples using a multivariate regression model. The predicted values provided by our model were found to be comparable to those obtained by immune complex kinase assays. Note: This abstract was not presented at the meeting. Citation Format: Diana Zamora-Olivares, Tamer S. Kaoud, Lingyu Zeng, Mitchell Telles, Eric V. Anslyn, Kevin N. Dalby. Quantification of ERK activity in cancer cell lysates and tumor extract using differential sensing methods [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr 2172.
The prognostic impact of age in patients with triple-negative breast cancer.
Authors: C. Liedtke, O. Gluz, L. Kiesel, G. N. Hortobagyi, L. Pusztai, A. M. Gonzalez-Angulo
Journal: Journal of Clinical Oncology (2010)

597 Background: Triple-negative breast cancer (TNBC) is characterized by lack of expression of estrogen and progesterone receptor as well as lack of overexpression/amplification of HER2/neu. Patients with TNBC suffer from a particularly unfavorable prognosis. We investigate the prognostic impact of age at diagnosis among patients with TNBC. Methods: We performed a retrospective analysis of 1,896 patients with primary TNBC. Patients were stratified according to age at diagnosis (≤40, 41-50, 51-60, >60 years). Additional patient characteristics comprised tumor size, nodal stage, nuclear grade, treatment characteristics and family history. Statistical analysis was performed using chi-square, log-rank, and Kaplan-Meier as well as Cox regression analysis (as a model including tumor size, nodal status, administration of adjuvant chemotherapy, grade, and family history). Results: Patients with TNBC aged ≤40 compared to patients aged >60 years were more often diagnosed with grade 3 tumors (93.5% vs. 82.5%, p<0.0001) and were more likely to have received cytotoxic neoadjuvant (36.2 vs. 24.4%, p=0.004) and adjuvant chemotherapy (62.0% vs. 43.0%, p<0.0001). Neoadjuvant chemotherapy response rates did not differ between age groups (p=0.898). Interestingly, patients ≤ 40 years at diagnosis showed significantly decreased median deasease-free survival (DFS) (p<0.001, see Table), distant disease-free survival (DDFS) (p<0.001) and even overall survival (OS) (p=0.002) compared to older patients. In multivariate analysis, age ≤40 years was a significant independent predictor of decreased DFS as well as large tumor size (<0.0001), positive nodal status, lack of administration of adjuvant chemotherapy, grade, use of adjuvant chemotherapy and family history with a trend for grade 3 tumors (p=0.059). Conclusions: Patient age at diagnosis younger than 40 years comprises an important and clinically significant unfavorable prognostic factor among patients with TNBC independent of nodal status, tumor size and use of chemotherapy. 95%CI Median DFS Lower limit Upper limit 31-40 398 40 29 52 41-50 569 90 66 115 51-60 541 99 58 140 > 60 years 374 111 60 161 No significant financial relationships to disclose.
Distinct Patterns of Neural Habituation and Generalization in Children and Adolescents With Autism With Low and High Sensory Overresponsivity
Authors: Shulamite A. Green, Leanna Hernandez, Katherine E. Lawrence, Janelle Liu, Tawny Tsang, Jillian Yeargin, Kaitlin Cummings, Elizabeth Laugeson, Mirella Dapretto, Susan Y. Bookheimer
Journal: American Journal of Psychiatry (2019)

Sensory overresponsivity (SOR), an atypical negative reaction to sensory stimuli, is highly prevalent in autism spectrum disorder (ASD). Previous work has related SOR to increased brain response in sensory-limbic regions. This study investigated where these atypical responses fall in three fundamental stages of sensory processing: arousal (i.e., initial response), habituation (i.e., change in response over time), and generalization of response to novel stimuli. Different areas of atypical response would require distinct intervention approaches.Functional MRI was used to examine these patterns of neural habituation to two sets of similar mildly aversive auditory and tactile stimuli in 42 high-functioning children and adolescents with ASD (21 with high levels of SOR and 21 with low levels of SOR) and 27 age-matched typically developing youths (ages 8-17). The relationship between SOR and change in amygdala-prefrontal functional connectivity across the sensory stimulation was also examined.Across repeated sensory stimulation, high-SOR participants with ASD showed reduced ability to maintain habituation in the amygdala and relevant sensory cortices and to maintain inhibition of irrelevant sensory cortices. These results indicate that sensory habituation is a dynamic, time-varying process dependent on sustained regulation across time, which is a particular deficit in high-SOR participants with ASD. However, low-SOR participants with ASD also showed distinct, nontypical neural response patterns, including reduced responsiveness to novel but similar stimuli and increases in prefrontal-amygdala regulation across the sensory exposure.The results suggest that all children with autism have atypical brain responses to sensory stimuli, but whether they express atypical behavioral responses depends on top-down regulatory mechanisms. Results are discussed in terms of targeted intervention approaches.
Abstract LB-180: Underreporting of race in genomic sequencing studies increases cancer health information disparities
Authors: Adrienne Nugent, Kelly R. Conatser, Llaran L. Turner, James T. Nugent, Esther May Sarino, Luisel J. Ricks-Santi
Journal: Cancer Research (2019)

Abstract Purpose: Minorities are often underrepresented in clinical cancer research and the frequency of reporting of race in genomic sequencing studies of cancer is unknown. Disproportionate reporting of race can widen health information disparities and impair clinical decision-making in the underrepresented minority populations in whom cancer disease burden is greatest. This study determined the extent to which race is reported as a clinical variable in sequencing studies of cancer in the United States, the factors associated with reporting of race, and the participation rates of minority populations. Methods: PubMed was systematically searched from January 1, 2010 through November 15, 2018 and a total of 9,410 non-duplicated studies were assessed for eligibility. Publications reporting whole genome or exome sequencing data for patients with one of the ten most common cancers in the United States at sufficient depth to identify rare variants were included in this study. Results: 234 publications containing sequencing data from 16,358 unique patients met inclusion criteria. 36% of studies reported race as a clinical variable compared to 84% of studies reporting age and 83% of studies reporting gender. Reporting of race was associated with cancer type, cohort size, sequencing method, and tissue acquisition date. Minority populations were significantly underpowered to detect recurrent mutations in the majority of cancer types due to small sample size. Conclusion: Race is underreported as a clinical variable in whole genome and exome sequencing studies of cancer in the United States. As the patient populations represented in research studies directly inform clinical decision-making and outcomes, substantially increased efforts are needed to sequence patients from underrepresented populations in order to reduce health disparities in patients of non-European ancestry. Citation Format: Adrienne Nugent, Kelly R. Conatser, Llaran L. Turner, James T. Nugent, Esther May Sarino, Luisel J. Ricks-Santi. Underreporting of race in genomic sequencing studies increases cancer health information disparities [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr LB-180.
Esophageal cancer: 5 years of experience in a Mexican oncology reference center
Authors: C. Salazar-Mejia, A. Burguete-Torres, O. Vidal-Gutierrez, D. Hernández Barajas, O. Borjas-Almaguer, B. Wimer-Castillo, J. Cessa-Zanatta
Journal: Annals of Oncology (2019)
The whistleblowing drama behind Astellas’s suspension from the ABPI
Authors: Deborah Cohen, Shai Mulinari, Piotr Ozieranski
Journal: BMJ (2019)

The Japanese drug company Astellas has had its knuckles rapped for wrongdoing four times in less than three years. Now <b>Deborah Cohen</b>, <b>Shai Mulinari</b>, and <b>Piotr Ozieranski</b> reveal fresh claims about the treatment of an employee who offered to help it clean up its act
Disappearance of the National Guideline Clearinghouse
Authors: Karen Schoelles
Journal: Annals of Internal Medicine (2019)

Letters2 July 2019Disappearance of the National Guideline ClearinghouseKaren Schoelles, MD, SMKaren Schoelles, MD, SMECRI Institute, Plymouth Meeting, Pennsylvania (K.S.)Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/L19-0151 SectionsAboutFull TextPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail TO THE EDITOR:I read Munn and colleagues' commentary (1) with interest. ECRI Institute served as the contractor of the Agency for Healthcare Research and Quality (AHRQ's) to develop and maintain the National Guideline Clearinghouse since its inception 20 years ago. The Institute will continue to provide a repository of summaries of current, evidence-based clinical practice guidelines. The Web site (www.ecri.org/guidelines), which is funded by a grant from the Gordon and Betty Moore Foundation, will enable users to search and retrieve its summarizations of guidelines and evaluations of the rigor and transparency of these guidelines against the National Academy of ...Reference1. Munn Z, Qaseem A; American College of Physicians and the Joanna Briggs Institute.. Disappearance of the National Guideline Clearinghouse: a huge loss for evidence-based health care. Ann Intern Med. 2018;169:648-9. [PMID: 30167676]. doi:10.7326/M18-2216 LinkGoogle Scholar Author, Article, and Disclosure InformationAffiliations: ECRI Institute, Plymouth Meeting, Pennsylvania (K.S.)Disclaimer: Dr. Schoelles is an employee of ECRI Institute.Disclosures: Disclosures can be viewed at www.acponline.org/authors/icmje/ConflictOfInterestForms.do?msNum=L19-0151. PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetailsSee AlsoDisappearance of the National Guideline Clearinghouse: A Huge Loss for Evidence-Based Health Care Zachary Munn , Amir Qaseem , and Disappearance of the National Guideline Clearinghouse Arlene S. Bierman and Mary P. Nix Metrics 2 July 2019Volume 171, Issue 1Page: 71KeywordsDisclosureHealth care qualityHealth services researchResearch quality assessmentTreatment guidelines ePublished: 2 July 2019 Issue Published: 2 July 2019 Copyright & PermissionsCopyright © 2019 by American College of Physicians. All Rights Reserved.PDF downloadLoading ...