tbuckley/cabot-search huggingface dataset:
Abstract 331: Genome-wide Analysis of Cardiac and Cardiac Fibroblasts Regulatory Elements Reveals Combinatorial Control of Gene Expression
Authors: Tal Golan Lagziel, Lilac Caspi, Yair Lewis, Izhak Kehat
Journal: Circulation Research (2017)

The mammalian body contains several hundred cell types that share the same genome, but can express distinct gene signatures. This specification of gene expression is achieved through the activity of cis-regulatory genomic elements (CRE), such as enhancers, promoters, and silencers. The Assay for Transposase-Accessible Chromatin followed by sequencing (ATAC-seq) can identify nucleosome evicted open chromatin, an established marker of regulatory regions. Using a differential ATAC-seq approach, coupled with RNA-seq, H3K27ac ChiP-seq, and computational transcription factor (TFs) binding analysis we comprehensively mapped cell-type and condition specific cis regulatory elements for cardiac fibroblasts and cardiomyocytes, and outlined the TFs that control them. We show that in cardiomyocytes six main transcription factor groups, that control their own and each other’s expression, cooperatively bind discrete distal enhancers that are located at a variable distance from the transcription start site of their target genes. None of these factors is entirely tissue specific in expression, yet various combination of binding sites for these factors, densely clustered within a nucleosome length of genomic stretch make these CREs tissue specific. Multiple tissue specific CREs in turn, are clustered around highly tissue specific genes, and multiple factors, acting from the same and from different CREs can converge on these genes to control their tissue specific expression. Together our data puts forward a mechanistic multi-level combinatorial model for cardiac specific genes expression
Возможность замены внутривенной формы омепразола на пероральную у пациентов с язвенным кровотечением
Authors: A.V. Savustyanenko
Journal: GASTROENTEROLOGY (2014)

Результаты исследований свидетельствуют об одинаковой терапевтической эффективности пероральной и внутривенной форм омепразола у пациентов с язвенным кровотечением. При этом препарат должен назначаться в высокой дозе (при пероральном приеме первая доза 80 мг, затем 40 мг через каждые 12 ч). Назначение пероральной формы омепразола экономически более выгодно в связи с более дешевой стоимостью таблеток и возможностью выписывать пациентов из стационара в более ранние сроки. Ингибиторы протонной помпы более эффективны и экономически более выгодны по сравнению с Н2-блокаторами у пациентов с язвенными кровотечениями.Большинство исследователей считает, что уже в ближайшем будущем будут пересмотрены действующие руководства по ведению больных с язвенным кровотечением в пользу замены рекомендаций по использованию внутривенных форм ингибиторов протонной помпы на пероральные.
Performance of Fully Automated Plasma Assays as Screening Tests for Alzheimer Disease–Related β-Amyloid Status
Authors: Sebastian Palmqvist, Shorena Janelidze, Erik Stomrud, Henrik Zetterberg, Johann Karl, Katharina Zink, Tobias Bittner, Niklas Mattsson, Udo Eichenlaub, Kaj Blennow, Oskar Hansson
Journal: JAMA Neurology (2019)

Accurate blood-based biomarkers for Alzheimer disease (AD) might improve the diagnostic accuracy in primary care, referrals to memory clinics, and screenings for AD trials.To examine the accuracy of plasma β-amyloid (Aβ) and tau measured using fully automated assays together with other blood-based biomarkers to detect cerebral Aβ.Two prospective, cross-sectional, multicenter studies. Study participants were consecutively enrolled between July 6, 2009, and February 11, 2015 (cohort 1), and between January 29, 2000, and October 11, 2006 (cohort 2). Data were analyzed in 2018. The first cohort comprised 842 participants (513 cognitively unimpaired [CU], 265 with mild cognitive impairment [MCI], and 64 with AD dementia) from the Swedish BioFINDER study. The validation cohort comprised 237 participants (34 CU, 109 MCI, and 94 AD dementia) from a German biomarker study.The cerebrospinal fluid (CSF) Aβ42/Aβ40 ratio was used as the reference standard for brain Aβ status. Plasma Aβ42, Aβ40 and tau were measured using Elecsys immunoassays (Roche Diagnostics) and examined as predictors of Aβ status in logistic regression models in cohort 1 and replicated in cohort 2. Plasma neurofilament light chain (NFL) and heavy chain (NFH) and APOE genotype were also examined in cohort 1.The mean (SD) age of the 842 participants in cohort 1 was 72 (5.6) years, with a range of 59 to 88 years, and 446 (52.5%) were female. For the 237 in cohort 2, mean (SD) age was 66 (10) years with a range of 23 to 85 years, and 120 (50.6%) were female. In cohort 1, plasma Aβ42 and Aβ40 predicted Aβ status with an area under the receiver operating characteristic curve (AUC) of 0.80 (95% CI, 0.77-0.83). When adding APOE, the AUC increased significantly to 0.85 (95% CI, 0.82-0.88). Slight improvements were seen when adding plasma tau (AUC, 0.86; 95% CI, 0.83-0.88) or tau and NFL (AUC, 0.87; 95% CI, 0.84-0.89) to Aβ42, Aβ40 and APOE. The results were similar in CU and cognitively impaired participants, and in younger and older participants. Applying the plasma Aβ42 and Aβ40 model from cohort 1 in cohort 2 resulted in slightly higher AUC (0.86; 95% CI, 0.81-0.91), but plasma tau did not contribute. Using plasma Aβ42, Aβ40, and APOE in an AD trial screening scenario reduced positron emission tomography costs up to 30% to 50% depending on cutoff.Plasma Aβ42 and Aβ40 measured using Elecsys immunoassays predict Aβ status in all stages of AD with similar accuracy in a validation cohort. Their accuracy can be further increased by analyzing APOE genotype. Potential future applications of these blood tests include prescreening of Aβ positivity in clinical AD trials to lower the costs and number of positron emission tomography scans or lumbar punctures.
Overuse of Urine Eosinophils in the Diagnosis of Acute Interstitial Nephritis
Authors: Anna Strasma, Shradha A. Kulkarni
Journal: JAMA Internal Medicine (2019)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA Internal Medicine HomeNew OnlineCurrent IssueFor Authors Podcast Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA Internal Medicine journal
PS1338 TEMPORAL TRENDS IN TRANSFUSION BURDEN AMONG NEWLY DIAGNOSED PATIENTS WITH MYELODYSPLASTIC SYNDROMES: A U.S. CLAIMS DATABASE STUDY
Authors: S.L. Slabaugh, E.S. Mearns, R. Copher, J. Johnson, P. Buzinec, S. Mukherjee
Journal: HemaSphere (2019)

Background: Myelodysplastic syndromes (MDS) are a heterogeneous group of clonal hematologic stem cell disorders characterized by ineffective hematopoiesis resulting in peripheral cytopenias. Anemia is the most prevalent of all cytopenias and is often treated with red blood cell transfusion (RBCT). There is a paucity of data on how the transfusion requirements of MDS patients change early in their clinical course. Understanding the temporal changes in transfusion needs in patients with MDS can provide data on the clinical need of MDS‐specific therapies based on the pace and burden of transfusion dependency. Aims: This retrospective study assessed the status and temporal trends in RBCTs among newly diagnosed patients with MDS in the United States, using a large administrative claims data set, Optum Research Database. Methods: All patients aged ≥ 18 years with newly diagnosed MDS (≥ 2 medical claims with an International Classification of Diseases, 9th or 10th Revision [ICD‐9 or ICD‐10] diagnosis codes ≥ 30 days apart) and in continuous health plan enrollment for ≥ 6 months pre‐ and 3 months post‐index date between January 2012 and May 2018 were included. Index was defined as date of first diagnosis. Transfusion status was evaluated during the 6‐month pre‐, and at 3‐month, 6‐month, and 9‐month post‐index periods for patients managed with observation alone, or with RBCT with or without erythropoiesis‐stimulating agents (ESAs). Transfusion independence (TI) was defined as patients receiving no transfusions; transfusion users (TU) was defined as 1 transfusion episode; and transfusion dependence (TD) was defined as patients receiving ≥ 2 transfusions during the observation periods. Results: Among the 3,803 patients identified, 56.3% were male, 85.4% were ≥ 65 years old (median age was 76), 78.0% were enrolled in a Medicare Advantage with Part D plan, and mean Quan‐Charlson Comorbidity Index was 1.98. Most patients (61.7%) were diagnosed with MDS, unspecified (ICD‐9‐CM 238.75, ICD‐10‐CM D46.9) on index date. Anemia was the presenting cytopenia in 78.8% of patients and 24.4% needed ≥ 1 RBCT (11.5% were TD and 12.9% were TU) preceding the MDS diagnosis. Common comorbidities observed in the pre‐index period were: hypertension (69.6%), cardiac diseases (58.1%), and dyslipidemia (54.8%). ESAs were administered to 40.7% of patients during the post‐index period. During the 9 months following diagnosis, a steady increase in TD was observed (Table). Summary/Conclusion: Disease burden in patients with MDS remains considerable. Considering that RBCT needs increased steadily despite ESA use with up to 37% still reliant on RBCT at 9 months post diagnosis indicates a critical unmet need for newer therapies for MDS patients who have TD anemia and for whom limited therapies exist beyond ESAs and RBCT. image
NHS needs to “cross the rubicon” of explaining service closures to patients, regional health boss says
Authors: Tom Moberly
Journal: BMJ (2019)

The NHS still needs to work out how to explain service closures to patients, the leader of a local health system has said.

Pat Flaherty, sustainability and transformation partnership lead for Somerset, said that he saw communicating service change as one of the key challenges lying ahead for the NHS. Flaherty, who is also chief executive of Somerset County Council, raised the matter …
An in situ microenvironmental nano-regulator to inhibit the proliferation and metastasis of 4T1 tumor
Authors: Huijuan Zhang, Xiaoge Zhang, Yanping Ren, Fang Cao, Lin Hou, Zhenzhong Zhang
Journal: Theranostics (2019)

Tumor microenvironment, such as hypoxia and presence of immune cells, plays a critical role in cancer initiation, growth as well as progression, and seriously affects antitumor effect. Accordingly, we constructed a kind of multifunctional nanoparticles (NPs) with macrophage transformation and oxygen (O2) generation characteristics, to regulate the tumor microenvironment. Methods: In this study, we synthesized mesoporous Prussian blue (MPB) NPs with low molecular weight hyaluronic acid (LMWHA) surface modification (LMWHA-MPB), and discovered that LMWHA-MPB could be used as an in situ macrophages converter and O2 generator. Results:In vitro results showed after uptake by M2 macrophages, LMWHA-MPB displayed the potential in remodeling tumor-associated macrophages (TAMs) phenotype (pro-tumor M2→anti-tumor M1), and anti-metastatic effect on 4T1 cells. Furthermore, in vivo visualized near-infrared (NIR) imaging data proved IR783 labeled LMWHA-MPB NPs could selectively accumulate in tumor sites. Then plenty of O2 generated to alleviate tumor hypoxia via catalytic decomposition of endogenous hydrogen peroxide (H2O2). Based on these outstanding characteristics, LMWHA-MPB NPs were adopted as multifunctional nanocarriers to load sonosensitizer hematoporphyrin monomethyl ether (HMME) for O2 self-provided sonodynamic therapy (SDT). In vivo anti-tumor results showed LMWHA-MPB/HMME could effectively inhibit the proliferation and metastasis of 4T1 tumors by improving tumor microenvironment. Conclusion: The multifunctional NPs can be used as in situ microenvironmental nano-regulators to inhibit the proliferation and metastasis of 4T1 tumor.
In vivo liquid biopsy using Cytophone platform for photoacoustic detection of circulating tumor cells in patients with melanoma
Authors: Ekaterina I. Galanzha, Yulian A. Menyaev, Aayire C. Yadem, Mustafa Sarimollaoglu, Mazen A. Juratli, Dmitry A. Nedosekin, Stephen R. Foster, Azemat Jamshidi-Parsian, Eric R. Siegel, Issam Makhoul, Laura F. Hutchins, James Y. Suen, Vladimir P. Zharov
Journal: Science Translational Medicine (2019)

Noninvasive label-free photoacoustic detection of circulating tumor cells was demonstrated directly in the bloodstream of patients with melanoma.
PB1784 BCL-2 EXPRESSION IS A GOOD PREDICTOR OF PROGNOSIS FOR PATIENTS WITH DIFFUSE LARGE B CELL LYMPHOMA
Authors: W. Jandamnernpong, K. Prayongratana, K. Satayasoontorn, C. Laoruangroj, A. Leelasiri, W. Prayoonwiwat
Journal: HemaSphere (2019)

Background: Although diffuse large B cell lymphoma (DLBCL) is the most common subtype of lymphoma in all ethnic groups, it is highly heterogeneous in term of natural course of disease and treatment outcome. Previous studies indicated that patients with double expression of the MYC and BCL-2 associated with a poorer response to treatment and long-term survival. According to previous study indicated impact of MYC, but the impact for BCL-2 expression on prognosis is still controversial. Aims: To evaluate BCL-2 immunohistochemistry expression grading as a predictor of prognosis in DLBCL. Methods: Patients with de-novo DLBCL and treated with chemotherapy (CMT) with/without rituximab were included. Primary mediastinum B cell lymphoma, CNS lymphoma and HIV patients were excluded. We designed a four-grade BCL-2 scoring criteria, from 0 to 3+, to evaluate immunohistochemistry grade by hematopathologists (Gr0 = negative; 1+ ≤ 50%; 2+ < 75%; 3+ ≥75%). The treatment options for these patients were CHOP or intensified regimen (EPOCH, DA-EPOCH) ± rituximab. The intensified regimen was given in patients with double (BCL2+MYC+ or BCL6+MYC+) or triple expression. Progression-free survival (PFS) and overall survival (OS) rates were analyzed in accordance with level of BCL2 expression. Results: One hundred patients were included to this study with a median follow-up 22 months (range, 4-48 months). BCL-2, BCL-6, and MYC expression were presence in 65%, 63%, and 73% of patients, respectively. Double expression and triple expression were detected in 36% and 32% of patients, respectively. The survival analyses showed that patients with BCL-2 expression grade 0 had significant better outcome in PFS compared to other group (p-value = 0.046); however, OS was not significant (p-value = 0.207). Subgroup analysis showed that patients with both non-GCB and BCL-2 protein expression grade 0 had strongly significant better outcome in PFS (Figure 1). The analysis for impact of chemotherapy regimen on each subgroup showed that patients with BCL2 grade 0 received R-intensified CMT had a better survival outcome compared to the other groups (p-value = 0.048; Figure 2). Most of the patients with BCL2 grade 0 who received R-intensified CMT were patients with double expression of BCL-6 and MYC indicated that these patients respond well to intensified regimen.Summary/Conclusion: BCL-2 expression was an independent prognostic factor in DLBCL and probably starts the cut-point of ≥1+ to predict treatment outcome.
BayFish: Bayesian inference of transcription dynamics from population snapshots of single-molecule RNA FISH in single cells
Authors: Mariana Gómez-Schiavon, Liang-Fu Chen, Anne E. West, Nicolas E. Buchler
Journal: Genome biology (2017)

Single-molecule RNA fluorescence in situ hybridization (smFISH) provides unparalleled resolution in the measurement of the abundance and localization of nascent and mature RNA transcripts in fixed, single cells. We developed a computational pipeline (BayFish) to infer the kinetic parameters of gene expression from smFISH data at multiple time points after gene induction. Given an underlying model of gene expression, BayFish uses a Monte Carlo method to estimate the Bayesian posterior probability of the model parameters and quantify the parameter uncertainty given the observed smFISH data. We tested BayFish on synthetic data and smFISH measurements of the neuronal activity-inducible gene Npas4 in primary neurons.
Abstract 15008: Results of the Brazilian Get With the Guidelines Program
Authors: Fabio P Taniguchi, Sabrina Bernardez-Pereira, Suzana A Silva, Camila P Pinto, Erica Morosov, Bernardete Weber, Enia L Coutinho, Luiz G Passaglia, Antonio L Ribeiro, Joao D Souza Neto, Vera L Pessoa, Sergio Montenegro, Dario C Sobral Filho, Luis E Rohde, Mariana V Furtado, Denilson C Albuquerque, Maria E Magalhães, Kleber R Pereira, Sheila Santos, Maria A Rivera, Ivan R Rivera, Marco A Guedes, Daniela C Dorta, Vitor S Barzilai, Diego M Mesquita, Marilia Vasconcelos, Tereza C Guimarães, Jose A Figueiredo Neto, Rafael A Gomes, Louise Morgan, Anne Curtis, Kathryn Taubert, SmithSidney C, Angelo A Paola
Journal: Circulation (2018)

Introduction: Quality improvement programs have shown a positive impact on important patient outcomes but data from developing countries are scarce. A Best Practice in Cardiology (BPC) program has ...
Ethnic differences in tumor proliferation in women with early-stage breast cancer.
Authors: Kevin Kalinsky, Emerson A. Lim, Eleni Andreopoulou, Avni Mukund Desai, Antai Wang, Matthew A. Maurer, Katherine D. Crew, Heather Greenlee, Hanina Hibshoosh, Joseph A. Sparano, Dawn L. Hershman
Journal: Journal of Clinical Oncology (2013)

560 Background: Hispanic women have a higher mortality rate and lower incidence of breast cancer (BC) compared to Caucasian women. Studies report higher tumor proliferation in African American (AA) women compared to Caucasian women. The 21-gene assay (OncotypeDX) Recurrence Score (Score) is based on the expression of 16 cancer related genes, including 5 proliferation genes that are grouped to provide the proliferation axis score (PAS). We evaluated the differences in the Score and PAS between Hispanic and Caucasian women with early-stage BC in a matched cohort analysis. Methods: Women with early-stage BC who had a Score obtained from 2005- 2011 were identified. Hispanic women were matched to Caucasians in a 1:2 ratio, based on age (+/- 10 years), stage, and nodal status. Lymphovascular invasion (LVI) and grade were collected. The Score result, 10-year distant recurrence, ER/PR/HER2 expression, and PAS were obtained from the OncotypeDX assay. Assuming equal variances, we expected &gt; 90% power to detect a difference in the mean PAS between Hispanic and Caucasian women Results: We identified 219 women who had OncotypeDX testing (74 Hispanic: 145 Caucasian). Of the 74 Hispanic women, 84% were from the Dominican Republic or Puerto Rico. Mean age was similar between groups (56.3 and 56.8). All but 8 patients were node(-). Mean PAS was higher in Hispanic (5.53, range: 3.9-7.8) vs Caucasian women (5.26, 3.7-7.3) (p=0.03, 95% CI: 0.03-0.51). The mean Score was 18.3 (0-54) and 16.3 (1-50) for Hispanic vs Caucasian women. There was no statistical difference in Score (p= 0.17) or 10-year distant recurrence (p=0.13) between groups. No differences were observed in median ER (9.8% vs 9.9%: Hispanic vs Caucasian), PR (7.3% vs 7.6%), or HER2 (9.1% vs 9.0%) by RT-PCR. Rates of LVI and grade 3 tumors were also not statistically different. Conclusions: Similar to higher PAS in AA women, Hispanic women with ER/PR(+), HER2(-) early-stage BC have higher tumor proliferation markers, measured by RT-PCR in the Oncotype DX assay, than Caucasian women. This may contribute to ethnic differences in BC mortality. We plan to evaluate ethnic differences in the 5 single PAS genes (CCNB1, MKI17, MYBL2, BIRC5, AURKA) to determine which are driving proliferation differences.
THU0036 ACTIVATED MEMORY T CELLS PRODUCE LIGANDS THAT CAUSE NF-κB-DEPENDENT INFLAMMATORY ACTIVATION OF THE ENDOTHELIUM: IDENTIFICATION OF NOVEL THERAPEUTIC TARGETS
Authors: Kim Jeucken, Jan Piet van Hamburg, Sander W. Tas
Journal: Annals of the Rheumatic Diseases (2019)

<h3>Background</h3> Endothelial cells (EC) are important contributors to inflammation via expression of inflammatory mediators, including cytokines, chemokines and adhesion molecules. Production of these inflammatory mediators can be induced via canonical and NF-κB-inducing kinase (NIK)-dependent noncanonical NF-κB signalling. The ligands activating these pathways are well studied, but less is known about the cells producing ligands that can activate NF-κB signalling in EC. <h3>Objectives</h3> To study the effects of factors produced by activated memory T (T<sub>m</sub>) cells on NF-κB dependent inflammatory activation of EC. <h3>Methods</h3> CD4<sup>+</sup>CD45RO<sup>+</sup> memory T cells were isolated from healthy PBMC using MACS sorting and cultured in presence of anti-CD3 and anti-CD28 for 72h, after which supernatant was harvested. Endothelial cells were stimulated for 72h with 50% T<sub>m</sub> supernatant (T<sub>m</sub> sup) after which protein and RNA was harvested followed by analysis of NF-κB signalling and downstream expression of inflammatory mediators using qPCR and western blot. Culture supernatants were analysed by ELISA for various inflammatory mediators. To repress canonical NF-κB signalling an inhibitor of IKKβ (iIKKβ) was used and to repress NIK-dependent NF-κB signaling an inhibitor of NIK (iNIK) was used in the EC cultures. <h3>Results</h3> Stimulation with T<sub>m</sub> sup led to activation of both canonical NF-κB signalling (increased levels of phosphorylated IκBα) and noncanonical NF-κB signalling (increased p100 to p52 processing). After stimulation with T<sub>m</sub> sup EC had increased mRNA levels of all tested inflammatory mediators compared to non-treated cells. Gene expression of chemokines, cytokines, and growth factors (CXCL1, CXCL5, IL6, IL8 and GM-CSF) in T<sub>m</sub> sup stimulated EC was significantly reduced after treatment with iIKKβ and to a lesser, but still significant, extent after treatment with iNIK. Treatment with iIKKβ also led to a reduction in mRNA levels of the adhesion molecules VCAM-1 and ICAM-1, while this effect was less pronounced after iNIK treatment. Of note, treatment with either IKKβ or iNIK led to a significant reduction of CXCL5 in the culture supernatant of T<sub>m</sub> sup stimulated EC. <h3>Conclusion</h3> This study provides new insights into the cellular interactions leading to production of inflammatory mediators by EC. Our findings demonstrate that activated T<sub>m</sub> cells produce factors that can cause NF-κB-dependent inflammatory activation of EC. Targeting canonical NF-κB signaling via IKKβ or NIK-dependent NF-κB signaling reduces inflammatory activation of the endothelium and may be a potential novel therapeutic target. Disclosure of Interests: None declared