tbuckley/cabot-search huggingface dataset:
Abstract 1288: Endothelium-Dependent Hyperpolarizations Are Totally Dependent on Endothelial Nitric Oxide Synthases System -Lessons from Mice Lacking All Nitric Oxide Synthase Isoforms-
Authors: Aya Takaki, Keiko Morikawa, Yoshinori Murayama, Ender Tekes, Masato Tsutsui, Nobuyuki Yanagihara, Hiroaki Shimokawa
Journal: Circulation (2007)

Background: We have previously demonstrated in animals and humans that endothelium-derived hydrogen peroxide (H2O2) is an endothelium-derived hyperpolarizing factor (EDHF) and that endothelial nitr...
FRI0701-HPR EFFICACY OF INTERMITTENT AEROBIC EXERCISE ON SLEEP EFFICIENCY IN PATIENTS WITH RHEUMATOID ARTHRITIS. A RANDOMIZED CONTROLLED TRIAL
Authors: Katrine Løppenthin, Julie Midtgaard, Bente Appel Esbensen, Mikkel Ǿstergaard, Jesper Frank Christensen, Tanja Thomsen, Anders Tolver, Poul Jennum
Journal: Annals of the Rheumatic Diseases (2019)

<h3>Background</h3> Insomnia is seen in &gt;60% of patients with rheumatoid arthritis (RA). While cross-sectional studies have shown a positive association between regular physical activity and good sleep, there is a lack of knowledge on the effect of physical activity on insomnia in patients with RA. <h3>Objectives</h3> To examine the efficacy of intermittent aerobic exercise on sleep efficiency as well as the effect on fatigue and depressive symptoms. <h3>Methods</h3> 38 patients with RA were randomly assigned to either intermittent aerobic exercise training; 3 session/week for 6 weeks; intervention group (n=17) or usual care (controls group n=21). The primary outcome was change in polysomnography (PSG) assessed sleep efficiency while secondary outcomes included sleep (Pittsburgh Sleep Quality Index), fatigue (Bristol Rheumatoid Arthritis Fatigue Multi-Dimensional Questionnaire) and depression (The Center for Epidemiological Studies-Depression). <h3>Results</h3> Sleep efficiency improved significantly in the intervention group from baseline 0.84 (95% CI 0.80-0.87) to end of the intervention 0.88 (95% CI 0.84-0.92) p=0.03, while for the control group the mean change was not significant. No between-group difference in change was observed. Fatigue was significantly reduced in the intervention group compared to the control group -16.0 (95%CI -25.1 - -7,04), including physical fatigue -4.99 (95%CI -7.25 - -2.74), cognitive fatigue -2.43 (95%CI -4.22 - -0.63) and living with fatigue -2.50 (95%CI -4.45- -0.54). <h3>Conclusion</h3> An intermittent aerobic exercise intervention presented no statistically significant effect on sleep efficiency in patients with RA compared with usual care. However, significant between-group differences were seen in subjectively reported fatigue including physical fatigue and cognitive fatigue and on depressive symptoms. <h3>References</h3> [1] Loppenthin K, Esbensen BA, Jennum P, et al. Effect of intermittent aerobic exercise on sleep quality and sleep disturbances in patients with rheumatoid arthritis - design of a randomized controlled trial. BMC musculoskeletal disorders2014 <h3>Disclosure of Interests</h3> Katrine Løppenthin: None declared, Julie Midtgaard: None declared, Bente Appel Esbensen Speakers bureau: For Pfizer, Mikkel Ǿstergaard Grant/research support from: Abbvie, Celgene, Centocor, Merck, Novartis, Consultant for: Abbvie, BMS, Boehringer-Ingelheim, Celgene, Eli Lilly, Hospira, Janssen, Merck, Novartis, Novo, Orion, Pfizer, Regeneron, Roche, and UCB, Speakers bureau: Abbvie, BMS, Boehringer-Ingelheim, Celgene, Eli Lilly, Hospira, Janssen, Merck, Novartis, Novo, Orion, Pfizer, Regeneron, Roche, and UCB, Jesper Frank Christensen: None declared, Tanja Thomsen: None declared, Anders Tolver: None declared, Poul Jennum: None declared
18F-FDG Whole-body PET/MRI of a 30-Week Pregnant Woman With Breast Cancer Revealed Interesting Fetal Findings
Authors: Paul Blanc-Durand, Milan Milliner, Virginie Huchet, Alain Luciani, Emmanuel Itti
Journal: Clinical Nuclear Medicine (2019)

Abstract A 35-year-old 30-week pregnant woman was referred to our institution for initial staging of a triple negative invasive ductal carcinoma of the left breast. To avoid fetal radiation exposure from CT, a whole-body 18 F-FDG PET/MRI was performed. Simultaneous acquisition of PET, T1-, T2-, and diffusion-weighted sequences revealed left axillary node extension and no distant metastases. Fetal radiation dose was estimated at 1.9 mGy. Interestingly, low fetal brain uptake and high symmetrical myocardial metabolism in both ventricles were found. Delivery was induced at 37 weeks of amenorrhea, and the patient underwent 4 cycles of neoadjuvant chemotherapy.
More friend than foe: the emerging role of neutrophils in tissue repair
Authors: Moritz Peiseler, Paul Kubes
Journal: Journal of Clinical Investigation (2019)

Neutrophils are the most abundant immune cells in humans and serve as first responders to a myriad of host perturbations. Equipped with a plethora of antimicrobial molecules, neutrophils invade sites of inflammation to eradicate pathogens and clear debris. Traditionally, neutrophils were thought to cause collateral tissue damage before dying at the site. However, the presence of neutrophil infiltration into sterile injuries (in the absence of infections) suggests additional roles for these cells. Now, the view of neutrophils as indiscriminate killers seems to be changing as evolving evidence suggests that neutrophils actively orchestrate resolution of inflammation and contribute to tissue repair. Novel concepts include the idea that neutrophils are key to revascularization and subsequently reverse-transmigrate back to the vasculature, actively leaving sites of tissue damage to re-home to functional niches in the lung and bone marrow. This Review scrutinizes the role of neutrophils in tissue damage and repair, discussing recent findings and raising unresolved questions around this intriguing immune cell.
Tobacco industry’s investment in sweetness comes full circle
Authors: Sven-Eric Jordt, Sairam Jabba
Journal: BMJ (2019)

Nguyen and colleagues clearly describe how the tobacco industry marketing juggernaut firmly established artificially flavoured, sugar sweetened drinks as part of children’s diets, contributing to today’s obesity and diabetes epidemic.1

Tobacco companies sold their sugary beverage assets years ago, but this groundwork probably underlies today’s strong preference of adolescents and young adults for intensely flavoured and sweetened tobacco products marketed by the same companies, including Reynolds and Altria (which owns Philip Morris). …
Abstract 13595: Folic Acid Protects Embryo From Environmental Effects on Lipid Metabolism During Cardiac and Placental Development
Authors: Kersti K Linask, Mingda Han
Journal: Circulation (2015)

Introduction: Congenital heart defects (CHDs) are the most prevalent of human birth defects with males exhibiting more severe types of CHDs. Cardiac cell and placental trophoblast differentiation are two embryonic processes occurring early between E6.5-E8.0 of mouse gestation (16-19 days of human pregnancy) that can be interfered with by environmental factors to induce anomalies. Objective: To determine the predominant pathway(s) targeted by exposures to lithium (Li+), homocysteine (HCys) , or alcohol (ethanol, EtOH) that result in CHDs and that can be protected by high dose folic acid (FA) supplementation. Method: On morning of conception, pregnant mice were placed on a protective, high FA diet (10 mg/kg) or on a health maintenance FA diet (3.3 mg/kg) that did not prevent CHDs. At gastrulation (E6.75) the mice received an i.p. injection of Li, HCys, or EtOH. Pregnant control groups received either the protective high FA or the normal FA maintenance diet and an i.p. injection of physiological saline only. Echocardiography on E15.5 determined embryos with abnormal cardiac function. All abnormal hearts and normal control hearts were removed, total RNA extracted. Microarrays were used to evaluate gene changes. Results: Significant expression changes among 12 treatment groups with Li and HCys exposures indicated that Gene Ontology (GO) categories involving lipid metabolism were chiefly altered. When the GO sets were sorted according to gender, male embryos displayed greater changes in lipid-related categories than the female. Validation studies demonstrated that Acyl CoA dehydrogenase medium length chain (Acadm) and its protein product important in fatty acid oxidation were modulated by the exposures, including by alcohol. Oil Red O (ORO) localization of neutral lipids in the heart and placenta demonstrated that lipids are highly altered possibly related to altered umbilical blood flow seen with embryos showing abnormal cardiac function. High FA restored normal ORO patterns, placental blood flow, and heart function. Conclusions: Li, HCys and alcohol exposed embryos display altered lipid metabolism. Early gestational supplementation with high-dose FA protects lipid metabolism at control levels, maintains placental physiology, and prevents CHDs.
Uptake of the 21-Gene Assay Among Women With Node-Positive, Hormone Receptor−Positive Breast Cancer
Authors: Megan C. Roberts, Allison W. Kurian, Valentina I. Petkov
Journal: Journal of the National Comprehensive Cancer Network (2019)

This study assessed uptake of the Oncotype DX 21-gene assay over time and characterized which sociodemographic and clinical factors are associated with test uptake among women with lymph node-positive (LN+), hormone receptor-positive, HER2-negative breast cancer.Invasive breast cancer cases diagnosed in 2010 through 2013 were included from a SEER database linked to 21-gene assay results performed at Genomic Health's Clinical Laboratory. Factors associated with 21-gene assay uptake were identified using a multivariable logistic regression model.Uptake of the 21-gene assay increased over time and differed by race, socioeconomic status (SES), and age. In the multivariable model, when clinical and SES variables were controlled for, racial differences in test uptake were no longer observed. Private insurance status was associated with higher odds of 21-gene assay uptake (Medicaid vs private insurance: adjusted odds ratio, 0.86; P=.02), and high area-level SES was associated with an increased odds of uptake (quintile 5 vs 1: adjusted odds ratio, 1.6; P<.001). Demographic factors such as age and marital status influenced test uptake, and use varied greatly by geographic region. Uptake of the 21-gene assay increased over time and preceded the assay's inclusion in the NCCN Guidelines for LN+ breast cancer. Differences in uptake by race, SES, and age have persisted over time. However, when clinical and SES variables were controlled for, racial differences in assay uptake were no longer observed. Socioeconomic variables, such as health insurance type and area-level SES, were associated with assay uptake.Future research should continue to document practice patterns related to the 21-gene assay. Given variation in testing associated with area-level SES, insurance coverage, and geographic region, interventions to understand and reduce differential uptake are needed to ensure equitable access to this genomic test.
AB0979 CORTICOSTEROID TREATMENT IN PEDIATRIC RHEUMATIC DISEASES AND SUPPRESSION OF THE HYPOTHALAMIC-PITUITARY AXIS
Authors: Teresa Giani, Francesca Falorni, Rolando Cimaz
Journal: Annals of the Rheumatic Diseases (2019)

<h3>Background</h3> Corticosteroids are the mainstay in the treatment of several chronic inflammatory diseases. Long-term treatment may lead to suppression of hypothalamic-pituitary-adrenal axis, which in turn can be dangerous in stress situations such as after surgical interventions. Oral replacement therapy may be needed in some cases. Data on pediatric populations are scanty. <h3>Objectives</h3> The aim of our study has been to evaluate hypothalamic-pituitary-adrenal function during corticosteroid tapering by measuring serum cortisol. <h3>Methods</h3> During long term corticosteroid treatment, serum cortisol levels were evaluated when oral prednisone dose was decreased to 7.5 mg/day and also after 4-6 weeks, and if below range ACTH levels were also determined. All patients aged &lt; 18 years seen in our center during the last 6 months who were on corticosteroid treatment for &gt; 1 month were included. Serum cortisol levels were considered normal if in the range of 5-25 µg/dL in a morning fasting blood drawing, while ACTH levels were considered normal in between 6 and 55 ng/L (with chemiluminescent method). Clinical and demographic data were recorded from clinical charts in a customized database. <h3>Results</h3> We have included in this preliminary study 12 patients (7F, 5M) affected by uveitis (n=4), JIA (n=4), scleroderma (n=3), lupus (n=1). The mean age (at the time of sampling) was 11.5 years, with a median of 10 and a range of 8-17. Prednisone starting dose was 1 mg/kg/day. Four out of 12 patients had decreased cortisol levels. Characteristics of these four patients (none of whom had additional steroid pulses) are detailed in the table. <h3>Conclusion</h3> One third of our patients had decreased cortisol levels, after three months of prednisone treatment. In one case, who showed persistent low levels, oral supplementation with hydrocortisone 20 mg/day for two months was needed. Our study is ongoing and results could help in identifying patients at risk for adrenal crisis. <h3>References</h3> [1] Gangadharan A, McCoy P, Phyo A, McGuigan MP, Dharmaraj P, Ramakrishnan R, McNamara PS, Blair J, "Recovery of hypothalamo-pituitary-adrenal axis suppression during treatment with inhaled corticosteroids for childhood asthma", J Asthma Allergy. 2017Dec15; [2] Sidoroff M, Kolho KL, "Screening for adrenal suppression in children with inflammatory bowel disease discontinuing glucocorticoid therapy", BMC Gastroenterol. 2014Mar24; [3] Ahmet A, Brienza V, Tran A, Lemieux J, Aglipay M, Barrowman N, Duffy C, Roth J, Jurencak R, "Frequency and Duration of Adrenal Suppression Following Glucocorticoid Therapy in ChildrenWith Rheumatic Diseases";Arthritis Care Res (Hoboken). 2017 Aug; <h3>Disclosure of Interests</h3> None declared
STRIDE: Species Tree Root Inference from Gene Duplication Events
Authors: David M Emms, Steven Kelly
Journal: Molecular Biology and Evolution (2017)

The correct interpretation of any phylogenetic tree is dependent on that tree being correctly rooted. We present STRIDE, a fast, effective, and outgroup-free method for identification of gene duplication events and species tree root inference in large-scale molecular phylogenetic analyses. STRIDE identifies sets of well-supported in-group gene duplication events from a set of unrooted gene trees, and analyses these events to infer a probability distribution over an unrooted species tree for the location of its root. We show that STRIDE correctly identifies the root of the species tree in multiple large-scale molecular phylogenetic data sets spanning a wide range of timescales and taxonomic groups. We demonstrate that the novel probability model implemented in STRIDE can accurately represent the ambiguity in species tree root assignment for data sets where information is limited. Furthermore, application of STRIDE to outgroup-free inference of the origin of the eukaryotic tree resulted in a root probability distribution that provides additional support for leading hypotheses for the origin of the eukaryotes.
Dysregulated Tgfbr2/ERK-Smad4/SOX2 Signaling Promotes Lung Squamous Cell Carcinoma Formation
Authors: Yanxiao Wang, Xiaohong Tan, Yuling Tang, Chong Zhang, Jiaqian Xu, Jian Zhou, Xuan Cheng, Ning Hou, Wenjia Liu, Guan Yang, Yan Teng, Xiao Yang
Journal: Cancer Research (2019)

Lung squamous cell carcinoma (SCC) is a common type of lung cancer. There is limited information on the genes and pathways that initiate lung SCC. Here, we report that loss of TGFβ type II receptor (Tgfbr2), frequently deleted in human lung cancer, led to predominant lung SCC development in KrasG12D mice with a short latency, high penetrance, and extensive metastases. Tgfbr2-loss-driven lung SCCs resembled the salient features of human lung SCC, including histopathology, inflammatory microenvironment, and biomarker expression. Surprisingly, loss of Smad4, a key mediator of Tgfbr2, failed to drive lung SCC; instead, low levels of phosphorylated ERK1/2, a Smad-independent downstream effector of Tgfbr2, were tightly associated with lung SCC in both mouse and human. Mechanistically, inhibition of phosphorylated ERK1/2 significantly upregulated the expression of SOX2, an oncogenic driver of lung SCC, and cooperated with SMAD4 repression to elevate SOX2. Inhibition of ERK1/2 in Smad4fl/fl ;KrasG12D mice led to extensive lung SCC formation that resembled the SCC phenotype of Tgfbr2-deficient mice. Overall, we reveal a key role of ERK1/2 in suppressing SCC formation and demonstrate that dysregulated Tgfbr2/ERK-Smad4/SOX2 signaling drives lung SCC formation. We also present a mouse model of metastatic lung SCC that may be valuable for screening therapeutic targets. SIGNIFICANCE: This study sheds new light on the mechanisms underlying lung SCC formation driven by mutated Kras.
PB2390 THE ROLE OF T REGULATORY CELLS IN THE PATHOGENS AND IMMUNITY OF BETA‐THALASSEMIA MAJOR PATIENTS
Authors: A. Adly, E. Ismail, M. Saleh, G. Hamed
Journal: HemaSphere (2019)

Background: The basis of the pathogenesis of the immunodeficiency in thalassemia is iron overload and allogenic stimulation caused by multiple blood transfusions. T regulatory cells (Tregs) are a component of the immune system that constitutes a key mechanism in maintaining peripheral self‐tolerance through the control of auto‐reactive lymphocyte activation. Aim: To determine the frequency of Tregs in children and adolescents with β‐thalassemia major and assessed their relation to the clinical and laboratory characteristics of patients including transfusion therapy, iron overload and alloimmunization. Methods: Sixty β‐TM patients studied focusing on transfusion history and chelation therapy. Hematological and biochemical data including markers of hemolysis and serum ferritin were assessed. Patients’ records were analyzed for the presence of alloantibodies. Assessment of T regulatory cells was done using flow cytometry. Patients were compared with 30 healthy controls. Results: The percentages of CD4 + T lymphocytes and Tregs were significantly reduced in β‐TM patients compared with the control group (p &lt; 0.05). Patients with patients with splenectomy, heart disease and pulmonary hypertension risk had lower levels of these cells than those without. The percentage of Tregs was decreased among patients with serum ferritin ≥2500 μg/L compared with patients below this cutoff and in patients with history of alloimmune antibodies. There were significant negative correlations between Tregs and each of indirect bilirubin and ferritin levels while they were positively correlated with WBCs counts and hemoglobin. Summary/Conclusion: Conclusion: Children and adolescents with β‐TM may encounter a state of immune dysfunction. Low frequency of Tregs in β‐TM patients may contribute to the formation of alloantibodies. Alterations in Tregs are more evident in relation to iron overload. It is important to assess the suppressive activity of these cells in standard proliferation assays to examine whether their function is disrupted in β‐TM together with the alteration in their frequency or not.
PB1888 FEATURES OF CYSTEIN-RICH PROTEIN METALLOTHIONEIN FUNCTIONING IN CHRONIC B-LYMPHOCYTIC LEUKEMIA CELLS
Authors: Y. Harmaza, A. Tamashevski, E. Slobozhanina
Journal: HemaSphere (2019)

Background: The main approach to the hematological cancers treatment is an intensive chemotherapy. However, often its ineffectiveness could be result of the phenomenon of multiple drug resistance (MDR) – immunity of cancer cells to cytostatic drugs. The most important MDR pathways are increased drug efflux resulting in reduced its accumulation, activation of detoxification mechanisms in tumor cells, altered activities of certain enzymes and level of intracellular thiols such as metallothioneins or reduced glutathione which bind compounds toxic for cells. Study and comprehension of these mechanisms will enable the design of suitable techniques and procedures for malignant tumor treatment. Aims: To investigate the level of expression of cystein-rich proteins metallothioneins in lymphocytes of patients with chronic B-lymphocytic leukemia (B-CLL) and to find out their role in the maintenance of redox state under this pathological state. Methods: Lymphocytes were separated from the B-CLL patient's and healthy donor's peripheral blood by density gradient centrifugation on histopaque. Monoclonal antibodies UC1MT (Abcam), UIC2 (Immunotech), MRP1 (R&D) were used to evaluate MTs I-II types, ABCB1, ABCC1 expression, respectively. Reactive oxygen species (ROS) level was assessed using fluorescent probe CM-H2DCFDA (Invitrogen). All investigations were carried out on the FACScanto II (BD). Results: A significant reduction (1.5–2.0-fold) of the MT expression level in B-CLL lymphocytes in comparison to the last one in healthy donors was reveled, despite the proven role of this protein in the detoxification processes from drugs. Additionally a comparative evaluation of expression of the membrane protein-transporters ABC family associated with MDR – ABCB1/P-gp and ABCC1/MRP1 was conducted. Theirs significant rise was found in tested group of B-CLL patients. Moreover, the rise of the ABCC1/ABCB1 expression ratio in leukemia cells reveled under enhanced ROS level compare to normal cells. Summary/Conclusion: Thus, in B-CLL cells the role of MT in the maintaining of redox state (ROS sequestration) is decreased under the rise of ABCC1 function. It is clear that the potential of MT as the scavengers of ROS is not fully understood, but the present data show that this protein could be selected as a target for novel treatment strategies for patients with leukemia.
Whorlton Hall: CQC denies publishing “whitewash” report of hospital accused of abusing patients
Authors: Adrian O’Dowd
Journal: BMJ (2019)

There was no cover up or whitewash of what took place at a specialist hospital for people with learning disabilities who were found to have been abused by staff,1 the regulator of the NHS in England, the Care Quality Commission, has told MPs and peers.

CQC officials appeared before the parliamentary joint committee on human rights during an evidence session on Wednesday 12 June as part of the committee’s inquiry into detention of children and young adults with learning disabilities or autism.

The session focused largely on the CQC’s inspection of the specialist hospital Whorlton Hall in County Durham, where abuse was exposed by the BBC’s Panorama television programme last month.2

Before the session the committee had asked the CQC for the previously unpublished findings of a 2015 inspection of Whorlton Hall, which the regulator submitted.

The committee’s chair, Harriet Harman, challenged the witnesses about the findings of the …
A New Index for Pre-Operative Cardiovascular Evaluation
Authors: Habib A. Dakik, Omar Chehab, Mahmoud Eldirani, Eman Sbeity, Cynthia Karam, Ossama Abou Hassan, Mayyas Msheik, Hussein Hassan, Ahmad Msheik, Chris Kaspar, Maha Makki, Hani Tamim
Journal: Journal of the American College of Cardiology (2019)