tbuckley/cabot-search huggingface dataset:
Abstract P220: The Effect of Diet-Induced Weight Loss on HDL Functionality in Individuals with Metabolic Syndrome: Investigating Alteration of the Initial Step in Reverse Cholesterol Transport as a Function of Plasma Lipoprotein Composition
Authors: Madhuri M Vasudevan, Urban Tchoua, Baiba Gillard, Hu Yu Lin, Peter Jones, Christie Ballantyne, Henry Pownall
Journal: Circulation (2012)

The prevalence of metabolic syndrome (MetS) with obesity-linked diabetes continues to increase globally and is associated with atherogenic dyslipidemia characterized by high triglycerides (TG), small, dense low-density lipoprotein cholesterol (LDL-C), and low high-density lipoprotein cholesterol (HDL-C) levels. HDL orchestrates the reverse cholesterol transport (RCT) process, initiated by macrophage cholesterol efflux (MCE). The traditional hypothesis is that individuals with dyslipidemia have impaired RCT that leads to atherogenesis. However, a recent study showed that one metric of HDL function, macrophage cholesterol efflux (MCE) to diluted patient plasma, inversely correlated with atherosclerotic burden, independent of plasma HDL-C levels. Moreover, cholesterol efflux from ABCA1-upregulated macrophage cell lines to sera of diabetic hypertriglyceridemic subjects is enhanced compared to normolipidemic (NL) controls. The effect of weight loss on MCE in obese individuals with MetS is unknown. The purpose of this study is to evaluate MCE in obese individuals with MetS as a function of plasma dyslipidemia, and to determine the effect of weight loss on the RCT process. We measured the rate of MCE from human monocytic leukemia THP1 cells to plasma of NL controls (n=24) and obese MetS (n=24) patients before and after 4 to 6 weeks of very low calorie, diet-induced weight loss. Weight loss in the MetS patients was significant, averaged 21.3 lbs, with concurrent significant decreases in TG, apoB, TC, LDL-C and non-HDL-C. Measures of insulin resistance, systolic blood pressure and kidney function improved with weight loss. HDL-C was not significantly altered, but apoA-I decreased with weight loss. MCE to plasma of obese MetS patients was higher than MCE to control plasma ((7.44 + 1.36) % vs (6.39 + 1.23) %, p=0.0069). MCE to plasma of obese MetS patients significantly decreased after weight loss (6.23 + 1.69) %, comparable to control values. MCE was strongly correlated to apoB levels (r 2 = 0.13 - 0.38), consistent with apoB lipoprotein function as a cholesterol sink. This was confirmed by size exclusion chromatography analysis of the distribution of effluxed cholesterol among plasma lipoproteins in 1 control and 2 Mets patients. In conclusion, obese patients with MetS demonstrate increased MCE, a measure of HDL function, compared to NL controls, which significantly decreases in response to diet-induced weight loss, concurrent with a reduction in triglyceride and apoB levels. These results suggest that the high apoB lipoprotein levels in MetS pateints facilitate MCE, and may at least partially compensate for the low HDL-C to promote RCT in these patients.
CBIO-34MiR-126 AND miR-369-5p ARE DRIVERS OF GBM INVASION: AN IN VIVO STUDY IN PATIENT-TUMOR DERIVED ORTHOTOPIC XENOGRAFT MOUSE MODELS
Authors: Lin Qi, Yulun Huang, Hua Mao, Mari Kogiso, Xiumei Zhao, Yuchen Du, Holly Lindsay, Patricia Baxter, Chris Man, Laszlo Perlaky, Zhong Wang, You-Xing Zhou, Xiao-Nan Li
Journal: Neuro-Oncology (2015)

We hypothesize that direct comparison of the matched invasive and tumor core GBM cells would facilitate the discovery of drivers of GBM invasion. However, GBM cells that infiltrate deep into  brain tissues (GBMinv) are extremely difficult to obtain from patients. To overcome this barrier, we utilized a panel of 7 (1 adult and 6 pediatric) patient-tumor derived orthotopic xenograft (PDOX) mouse models to isolate matched GBMinv and GBMTC cells by cutting whole mouse brains into 10 slices (1 mm thick), followed by microscopic dissection of tumor mass (to harvest GBMTC cells) and the normal mouse brains (to harvest GBMinv cells), respectively. After the mouse cells were decontaminated through FACS, matched GBMinv and GBMTC cells were subjected to microRNA profiling using Taqman MicroRNA array (768 microRNAs). Compared with the GBMTC cells, 23 microRNAs were upregulated in the GBMinv cells in at least 5 of the 7 GBM models. Functional validation showed that silencing miR-126 and mir-369-5p, the top two overexpressed microRNA in GBMinv, did not significantly alter cell proliferation but suppressed tumor cell migration (both as neurospheres and as monolayer cultures) in vitro. To confirm their role as drivers of GBM invasion in vivo, purified GBMinv cells were transduced with lentiviruses (silencing miR-126 and mir-369-5p, respectively) and implanted into the brains of NOD/SCID mice. Compared with the untreated parental cells and tumor cells transduced with non-target control lentiviruses, silencing miR-126 or miR-369-5p significantly suppressed GBM invasion. Not only the areas but also the depth of the invasive front were remarkably decreased, exhibiting sharp or well-demarcated margins between tumor and  mouse brains. In conclusion, we identified a set of microRNAs that are selectively over-expressed in the invasive front of GBM cells and functionally confirmed that miR-126 and miR-369-5p as drivers of GBM invasion.
Myeloid-Epithelial-Reproductive Receptor Tyrosine Kinase and Milk Fat Globule Epidermal Growth Factor 8 Coordinately Improve Remodeling After Myocardial Infarction via Local Delivery of Vascular Endothelial Growth Factor
Authors: Kiave-Yune Howangyin, Ivana Zlatanova, Cristina Pinto, Anta Ngkelo, Clément Cochain, Marie Rouanet, José Vilar, Mathilde Lemitre, Christian Stockmann, Bernd K. Fleischmann, Ziad Mallat, Jean-Sébastien Silvestre
Journal: Circulation (2016)

In infarcted heart, improper clearance of dying cells by activated neighboring phagocytes may precipitate the transition to heart failure. We analyzed the coordinated role of 2 major mediators of efferocytosis, the myeloid-epithelial-reproductive protein tyrosine kinase (Mertk) and the milk fat globule epidermal growth factor (Mfge8), in directing cardiac remodeling by skewing the inflammatory response after myocardial infarction.We generated double-deficient mice for Mertk and Mfge8 (Mertk(-/-)/Mfge8(-/-)) and challenged them with acute coronary ligature. Compared with wild-type, Mertk-deficient (Mertk(-/-)), or Mfge8-deficient (Mfge8(-/-)) animals, Mertk(-/-)/Mfge8(-/-) mice displayed greater alteration in cardiac function and remodeling. Mertk and Mfge8 were expressed mainly by cardiac Ly6C(High and Low) monocytes and macrophages. In parallel, Mertk(-/-)/Mfge8(-/-) bone marrow chimeras manifested increased accumulation of apoptotic cells, enhanced fibrotic area, and larger infarct size, as well as reduced angiogenesis. We found that the abrogation of efferocytosis affected neither the ability of circulating monocytes to infiltrate cardiac tissue nor the number of resident Ly6C(High) and Ly6C(How) monocytes/macrophages populating the infarcted milieu. In contrast, combined Mertk and Mfge8 deficiency in Ly6C(High)/Ly6C(Low) monocytes/macrophages either obtained from in vitro differentiation of bone marrow cells or isolated from infarcted hearts altered their capacity of efferocytosis and subsequently blunted vascular endothelial growth factor A (VEGFA) release. Using LysMCre(+)/VEGFA(fl/fl) mice, we further identified an important role for myeloid-derived VEGFA in improving cardiac function and angiogenesis.After myocardial infarction, Mertk- and Mfge8-expressing monocyte/macrophages synergistically engage the clearance of injured cardiomyocytes, favoring the secretion of VEGFA to locally repair the dysfunctional heart.
Reconstitution of the &lt;italic&gt;W/W&lt;/italic&gt;&lt;sup&gt;&lt;italic&gt;v&lt;/italic&gt;&lt;/sup&gt; Stem Cell Differentiation Defect by Infection With Rauscher Leukemia Virus&lt;xref ref-type="fn" rid="FN2"&gt;2&lt;/xref&gt;
Authors: S Merchav, G Wagemaker, D W van Bekkum
Journal: JNCI Journal of the National Cancer Institute (1985)

Hematopoietic stem cells of W/Wv mice failed to produce macroscopically visible hematopoietic spleen colonies in irradiated recipient mice. Infection of W/Wv mice of the spleen focus-forming virus-susceptible genotype Fv-2ss (DBA/2) or Fv-2rs (BD2F1) with Rauscher leukemia virus (RLV) restored the spleen colony-forming capacity of the stem cells. The resulting spleen colonies had normal size and cellularity; the frequency of and ratio between granulocyte-macrophage and erythroid progenitor cells were also normal, without excessive production of erythroid cells. The frequency of spleen colony-forming units (CFU-S) appeared to be strongly reduced in W/Wv mice. The seeding fraction of RLV-infected W/Wv stem cells in the recipient spleens did not differ from that of uninfected or RLV-infected +/+ stem cells. At equivalent numbers of CFU-S, spleen suspensions of RLV-infected W/Wv mice were equally effective as +/+ control suspensions in protecting irradiated mice from death due to bone marrow failure. Thus the number of CFU-S observed appeared to be predictive for the number of W/Wv cells required for effective radioprotection. In irradiated W/Wv mice that received transplants of RLV-infected W/Wv cells, circulating erythrocyte numbers approached those of control mice; the erythrocytes were of normal size, in contrast to the macrocytic red cells of untreated W/Wv mice. The reduced frequency of CFU-S in RLV-infected W/Wv mice can be readily explained by a reduced self-replicating capacity, attributable to the W/Wv genes, which was not reconstituted by infection with RLV. The data indicate a direct involvement of pluripotent stem cells upon infection with RLV.
Abstract 15606: Clevidipine Improves Dyspnea in Emergency Department Acute Heart Failure: A Randomized, Open Label Study
Authors: William F Peacock, Abhinav Chandra, Sean Collins, Gregg Fonarow, Norman Garrison, Alexandre Mebazaa
Journal: Circulation (2012)

Purpose: Dyspnea from hypertensive acute heart failure (AHF) may improve rapidly with BP reduction. Clevidipine (CLV), a short acting arteriospecific calcium antagonist may be effective in this coh...
Many Americans have problems with cost and access to healthcare, poll finds
Authors: Michael McCarthy
Journal: BMJ (2016)

While most Americans were satisfied with the healthcare they received, around 20% said that the quality had been “fair” to “poor,” and many reported having problems with the cost of, and access to, care, a new poll has found.1

The poll, conducted by National Public Radio, the Robert Wood Johnson Foundation, and Harvard TH Chan School of Public Health, surveyed 1000 adults nationwide and 1000 adults each in seven states—Florida, Kansas, New Jersey, …
Clinician-friendly physical performance tests in athletes part 3: a systematic review of measurement properties and correlations to injury for tests in the upper extremity
Authors: Daniel T Tarara, Lucas K Fogaca, Jeffrey B Taylor, Eric J Hegedus
Journal: British Journal of Sports Medicine (2015)

In parts 1 and 2 of this systematic review, the methodological quality as well as the quality of the measurement properties of physical performance tests (PPTs) of the lower extremity in athletes was assessed. In this study, part 3, PPTs of the upper extremity in athletes are examined.Database and hand searches were conducted to identify primary literature addressing the use of upper extremity PPTs in athletes. The Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines were followed and the Consensus-based Standards for the selection of health Measurement Instruments (COSMIN) checklist was used to critique the methodological quality of each paper. The Terwee Scale was used to analyse the quality of the measurement properties of each test.11 articles that examined 6 PPTs were identified. The 6 PPTs were: closed kinetic chain upper extremity stability test (CKCUEST), seated shot put (2 hands), unilateral seated shot put, medicine ball throw, modified push-up test and 1-arm hop test. Best evidence synthesis provided moderate positive evidence for the CKCUEST and unilateral seated shot put. Limited positive evidence was available for the medicine ball throw and 1-arm hop test.There are a limited number of upper extremity PPTs used as part of musculoskeletal screening examinations, or as outcome measures in athletic populations. The CKCUEST and unilateral seated shot put are 2 promising PPTs based on moderate evidence. However, the utility of the PPTs in injured populations is unsubstantiated in literature and warrants further investigation.
Differential role of Id1 in MLL-AF9–driven leukemia based on cell of origin
Authors: Na Man, Xiao-Jian Sun, Yurong Tan, Marta García-Cao, Fan Liu, Guoyan Cheng, Megan Hatlen, Haiming Xu, Ronit Shah, Nolan Chastain, Na Liu, Gang Huang, Yuan Zhou, Mengyao Sheng, Junhong Song, Feng-Chun Yang, Robert Benezra, Stephen D. Nimer, Lan Wang
Journal: Blood (2016)
Regression of Established Intradermal Tumors and Lymph Node Metastases in Guinea Pigs After Systemic Transfer of Immune Lymphoid Cells
Authors: H. G. Smith, R. P. Harmel, M.G. Hanna, B.S. Zwilling, B. Zbar, H. J. Rapp
Journal: JNCI Journal of the National Cancer Institute (1977)

Strain-2 male guinea pigs with established intradermal (id) tumors and microscopic regional lymph node metastases were treated by systemic transfer of syngeneic peritoneal exudate (PE) cells from tumor-immune guinea pigs. This treatment produced complete regressions of established id tumor nodules (10–11 mm in diameter) and prevented the growth of lymph node metastases in 32 (80%) of the 40 treated animals. All untreated animals died with progressive id and lymphatic tumor growth. Lymph node tumor metastases that remained after id tumor excision were also suppressed by immune cell transfer. PE cells from guinea pigs immune to an antigenically distinct tumor line (line-1), BCG, or PE cells from nonimmune guinea pigs failed to produce tumor regression or prolongation of survival time. PE cells from allogeneic guinea pigs and from sheep immune to line-10 failed to transfer tumor immunity to strain-2 guinea pigs. The effectiveness of therapy was reduced by increasing the tumor burden or decreasing the number of transferred lymphoid cells. This study demonstrated that systemic transfer of cells from syngeneic immune donors could effectively eliminate tumors as well as early metastases.
Zika cases climb to 147 in US and Puerto Rico
Authors: Michael McCarthy
Journal: BMJ (2016)

A total of 147 cases of Zika virus infection in the United States and Puerto Rico have been reported to the US Centers for Disease Control and Prevention as at 26 February. Of these, 107 occurred in 24 US states and 40 on the island of Puerto Rico.

In a teleconference briefing with reporters, the CDC’s director, Tom Frieden, said that all of the 107 cases reported within the US had been travel related but that most of the 40 cases reported in Puerto Rico had been acquired on the island through local transmission. “There is the potential for hundreds of thousands of Zika cases in Puerto Rico,” …
Chronicles of a cancer foretold: 35 years of gastric cancer risk assessment
Authors: Massimo Rugge, Robert M Genta, David Y Graham, Francesco Di Mario, Luiz Gonzaga Vaz Coelho, Nayoung Kim, Peter Malfertheiner, Kentaro Sugano, Vladislav Tsukanov, Pelayo Correa
Journal: Gut (2016)

In 1980, an international group of pathologists and clinicians led by Basil Morson published a critical review entitled Precancerous Conditions and Epithelial Dysplasia in the Stomach. 1 This seminal article attempted to merge Eastern and Western pathological experiences in the evaluation of preneoplastic conditions into a systematic approach to the evaluation of gastric precancerous conditions.Thirty-five years after its publication, we pay homage to Professor Morson's team by revisiting their positions in light of the dramatic advances of our understanding of gastric disease that have occurred during this time.To this end, we have selected from the original article those statements that warranted reappraisal and, after reproducing them verbatim, have provided our comments.
A cluster of Legionnaires' disease caused by Legionella longbeachae linked to potting compost in Scotland, 2008-2009
Authors: S J Pravinkumar, G Edwards, D Lindsay, S Redmond, J Stirling, R House, J Kerr, E Anderson, D Breen, O Blatchford, E McDonald, A Brown
Journal: Eurosurveillance (2010)

Binary file ES_Abstracts_Final_ECDC.txt matches
Abstract 16685: Depletion of Circulating CD34+/KDR+ Cells in Type 2 Diabetes is Associated With Glycemic Control
Authors: Nagma Zafar, Sathya S Krishnasamy, Jasmit Shah, James McCracken, Candice R Holden, Natasha K DeJarnett, Wesley T Abplanalp, Bradford Hill, Daniel Conklin, Timothy O’Toole, Shesh Rai, Aruni Bhatnagar
Journal: Circulation (2014)

Background and Hypothesis: Circulating levels of endothelial progenitor cells have been found to be predictive of cardiovascular events and mortality. Although the levels of these cells reflect overall cardiovascular disease (CVD) risk, studies assessing their association with major CVD factors - hypertension, dyslipidemia and diabetes have yielded inconsistent results and the mechanisms contributing to EPC depletion remain unknown. We hypothesized that EPC depletion occurring in diabetes is mediated in part by hyperglycemia or insulin resistance. Methods: Circulating levels of progenitor cells were measured by flow cytometry in 108 diabetic or non-diabetic subjects recruited from the University of Louisville Health System. Reactive hyperemia index (RHI) was measured by the EndoPAT. Demographic information was acquired and blood, plasma and urine were used for biochemical analyses. Subjects were divided into high and low EPC count groups using the median split. Data was analyzed using a Chi-square test, a two-sample rank sum test, and univariable and multivariable logistic regressions. Results: Levels of CD34 + /KDR + /CD14 − /CD16 − cells (EPCs) were associated with the diagnosis of diabetes (p=0.04), but not with other demographic covariates, hypertension or dyslipidemia. Levels of CD34 + , AC133 + and CD34 + /AC133 + /CD45 + cells also displayed significant association with diabetes (p=0.038, 0.014 and 0.038 respectively). RHI was strongly associated with diabetes (p&lt;0.0001) hypertension and dyslipidemia, however, no significant associations were observed between RHI and EPCs. EPC levels were inversely associated with HbA1C (p=0.047) and fasting blood glucose, but not with insulin levels or the HOMA-IR score. In the complete model, the association between EPCs and diabetes was strengthened by the inclusion of RHI, indicating more robust EPC depletion in those with endothelial dysfunction. Conclusion: Circulating EPC levels are a robust index of long-term glycemic control and are associated with hyperglycemia rather than contemporaneous insulin levels or endothelial dysfunction. These findings may help in prognosis and early identification of CVD risk in patients with diabetes, independent of other risk estimates.
The immunosuppressant rapamycin blocks in vitro responses to hematopoietic cytokines and inhibits recovering but not steady-state hematopoiesis in vivo
Authors: VF Quesniaux, S Wehrli, C Steiner, J Joergensen, HJ Schuurman, P Herrman, MH Schreier, W Schuler
Journal: Blood (1994)
Further studies of value of spiral computed tomography are needed
Authors: E. J R van Beek
Journal: BMJ (1998)

EDITOR—An editorial by Hansell and Flower dealt with the challenge of adequately diagnosing pulmonary embolism with spiral computed tomography.1Although I am in favour of changing one's diagnostic algorithm in line with improvements in diagnostic modalities, I would like to take a closer look at the proof in support of this new technique.

As the …
Bruton's Tyrosine Kinase Deficiency Inhibits Autoimmune Arthritis in Mice but Fails to Block Immune Complex–Mediated Inflammatory Arthritis
Authors: Lindsay E. Nyhoff, Bridgette L. Barron, Elizabeth M. Johnson, Rachel H. Bonami, Damian Maseda, Benjamin A. Fensterheim, Wei Han, Timothy S. Blackwell, Leslie J. Crofford, Peggy L. Kendall
Journal: Arthritis & Rheumatology (2016)

Objective Bruton's tyrosine kinase (BTK) is a B cell signaling protein that also contributes to innate immunity. BTK inhibitors prevent autoimmune arthritis but have off‐target effects, and the mechanisms of protection remain unknown. We undertook these studies using genetic deletion to investigate the role of BTK in adaptive and innate immune responses that drive inflammatory arthritis. Methods BTK‐deficient K/BxN mice were generated to study the role of BTK in a spontaneous model that requires both adaptive and innate immunity. The K/BxN serum‐transfer model was used to bypass the adaptive system and elucidate the role of BTK in innate immune contributions to arthritis. Results BTK deficiency conferred disease protection to K/BxN mice, confirming outcomes of BTK inhibitors. B lymphocytes were profoundly reduced, more than in other models of BTK deficiency. Subset analysis revealed loss of B cells at all developmental stages. Germinal center B cells were also decreased, with downstream effects on numbers of follicular helper T cells and greatly reduced autoantibodies. In contrast, total IgG was only mildly decreased. Strikingly, and in contrast to small molecule inhibitors, BTK deficiency had no effect in the serum‐transfer model of arthritis. Conclusion BTK contributes to autoimmune arthritis primarily through its role in B cell signaling and not through innate immune components.
Abstract 32: Investigating the Autoactivation of p38α Mitogen-Activated Protein Kinase Mediated by Transforming Growth Factor-β-Activated Protein Kinase Binding Protein 1
Authors: Gian Felice De Nicola, E D Martin, Rekha Bassi, Sharwari Verma, Maria Conte, Michael S Marber
Journal: Circulation Research (2012)

Activation of p38α MAPK (p38α), by phosphorylation of two residues in the TGY motif of the activation loop, can occur independently of upstream kinases. One such mechanism involves the scaffolding protein Transforming Growth Factor-β-activated protein kinase binding protein 1 (TAB1). Under certain circumstances, such as myocardial ischemia, this activation can aggravate lethal injury. It is one of a few examples of activating autophosphorylation and poses a conundrum. How does an inactive kinase, and therefore with low affinity for ATP, phosphorylate its own activation loop when ATP binding is a prerequisite step for phosphotransfer? The aim of this study was to characterize the TAB1 binding of p38α. The binding characteristics of p38α and TAB1 were determined by Isothermal Titration Calorimetry, followed by the binding of p38α and ATPγS, a slowly hydrolysable form of ATP, in the presence and absence of TAB1. The binding of TAB1 to p38α increased significantly the affinity of p38α for ATP. Following the identification of a key region in TAB1 responsible for p38α binding, a synthetic peptide encompassing this region was used to analyze the biophysical and biological consequences of TAB1 binding. In vitro kinase assays were used to test the biochemical characteristics using a combination of wildtype kinase, kinase dead (K53M) or both in the absence or presence of TAB1(371-416). Using an antibody specific to the dual phosphorylation of the TGY motif as a readout, TAB1 binding to p38α increased p38α autophosphorylation in cis . NMR was employed to map the interaction surfaces between of p38α and TAB1 and to analyze the effect of TAB1-binding on p38α. The residues identified as important for the interaction between TAB1 and p38α were mutated and tested in cell free and biological systems to confirm their role as critical determinants for binding. In conclusion, we have further elucidated a mechanism whereby TAB1 binding to p38α alters the conformation of p38α, increasing its affinity for ATP and thereby facilitating autophosphorylation. We have identified the binding contacts of TAB1 and p38α that may be important in the design of therapeutics enabling selective and circumstance-specific inhibition of p38α activation.