tbuckley/cabot-search huggingface dataset:
Hard Brexit could cripple UK science, warn top scientists
Authors: Matthew Limb
Journal: BMJ (2018)

Leading scientists have renewed warnings that a “hard” Brexit threatens European research progress, amid fresh signs that the UK will struggle to retain top scientists.

Paul Nurse, head of the Francis Crick Institute in London, said that exiting the EU without a deal in place could “cripple” UK science.

He was among 35 Nobel laureates and Fields medallists from around Europe to warn against new barriers emerging to scientific partnerships, in letters sent to the UK prime minister, Theresa May, and the European Commission president, Jean-Claude Juncker.1

The letters called for a Brexit deal on science and innovation that allows “the closest possible cooperation between the UK and the EU, now and in the future.” They highlighted the need for “the flow …
Kinetics of adult hematopoietic stem cell differentiation in vivo
Authors: Samik Upadhaya, Catherine M. Sawai, Efthymia Papalexi, Ali Rashidfarrokhi, Geunhyo Jang, Pratip Chattopadhyay, Rahul Satija, Boris Reizis
Journal: The Journal of Experimental Medicine (2018)

Adult hematopoiesis has been studied in terms of progenitor differentiation potentials, whereas its kinetics in vivo is poorly understood. We combined inducible lineage tracing of endogenous adult hematopoietic stem cells (HSCs) with flow cytometry and single-cell RNA sequencing to characterize early steps of hematopoietic differentiation in the steady-state. Labeled cells, comprising primarily long-term HSCs and some short-term HSCs, produced megakaryocytic lineage progeny within 1 wk in a process that required only two to three cell divisions. Erythroid and myeloid progeny emerged simultaneously by 2 wk and included a progenitor population with expression features of both lineages. Myeloid progenitors at this stage showed diversification into granulocytic, monocytic, and dendritic cell types, and rare intermediate cell states could be detected. In contrast, lymphoid differentiation was virtually absent within the first 3 wk of tracing. These results show that continuous differentiation of HSCs rapidly produces major hematopoietic lineages and cell types and reveal fundamental kinetic differences between megakaryocytic, erythroid, myeloid, and lymphoid differentiation.
Abstract 16226: 3d Cell Printed Cardiac Patch With Engineering Mesenchymal Stem Cells Improves Cardiac Function After Myocardial Infarction
Authors: Bong-Woo Park, Seok-Won Kim, Ju Ha Seo, Yu-mi Cho, Jinah Jang, Sang Hoon Park, Sung Mook Kim, Brandon S Ra, Hun-Jun Park, Dong-Woo Cho
Journal: Circulation (2017)

Background: A major challenge of the therapeutic use of stem cells for cardiac repair is poor cell engraftment in vivo after transplantation. 3D cell printing technology can rapidly create cardiac ...
GW29-e1041 The mechanism research of Bushen Kangshuai tablets affecting the progression of atherosclerosis by intervening Macrophages autophagy and polarization
Authors: Yingyu Xie, Lijun Tian, Zihan Fang, Aiqin Zhong, Shixin Xu, Junping Zhang
Journal: Journal of the American College of Cardiology (2018)
Effect of a workplace-based group training programme combined with financial incentives on smoking cessation: a cluster-randomised controlled trial
Authors: Floor A van den Brand, Gera E Nagelhout, Bjorn Winkens, Niels H Chavannes, Onno C P van Schayck
Journal: The Lancet Public Health (2018)

Financial incentives are potentially useful tools to aid smoking cessation, but robust evidence to support their efficacy, particularly in combination with other interventions (eg, group counselling), has not been reported. We aimed to investigate whether financial incentives combined with a smoking cessation group training programme (compared with a training programme with no incentives) organised at the workplace would increase 12-month abstinence rates in tobacco-smoking employees with different education and income levels.This cluster-randomised controlled trial was done in the Netherlands with companies that offer a smoking cessation group training programme to all of their smoking employees. Eligible participants were tobacco-smoking employees and spouses of employees who were at least 18 years of age. Participants in the control group received a weekly 90-min session of smoking cessation group training for 7 weeks at the workplace; in addition to the group training, participants in the intervention group received vouchers for being abstinent (€50 at the end of the training programme, €50 3 months after completion of the programme, €50 after 6 months, and €200 after 12 months). Companies were randomly assigned by an independent research assistant to the intervention group or the control group with a digital randomisation programme, using a biased urn method. The primary outcome was carbon monoxide-validated continuous abstinence at 12 months. All randomised participants were included in the modified intention-to-treat analyses, with the exception of unavoidable loss (participants who had died or moved to an untraceable address (according to the Russell Standard), and in the sensitivity analyses, except the complete case analysis, which included only participants for whom all variables included in the model were not missing. This study is registered with the Dutch Trial Register, number NTR5657.Between March 1, 2016, and March 1, 2017, 61 companies with 604 participating smokers were enrolled. 31 companies (319 smokers) were randomly assigned to the intervention group and 30 companies (285 smokers) to the control group. 12 months after finishing the smoking cessation programme, the proportion of individuals abstaining from smoking in the intervention group was significantly higher than that in the control group (131 [41%] of 319 vs 75 [26%] of 284; adjusted odds ratio 1·93, 95% CI 1·31-2·85, p=0·0009; adjusted for education level, income level, and Fagerström score).Financial incentives in addition to a smoking cessation group training programme can significantly increase long-term smoking abstinence. The results of the current study could motivate employers to facilitate a workplace smoking cessation programme with financial incentives to help employees to quit smoking.Dutch Cancer Society.
Use of Qtracker™ 655 to monitor the interaction of metastatic breast cancer cells with osteoblasts in co-culture
Authors: Laurie Shuman, Ravi Dhurjati, Venkatesh Krishnan, Gang Ning, Erwin Vogler, Andrea Mastro
Journal: Cancer Research (2007)

2805  Breast cancer metastasis to bone occurs frequently and results in the formation of painful osteolytic lesions. Bisphosphonates, drugs that inhibit osteoclasts, slow lesion progression; but pre-existing lesions do not heal, suggesting that breast cancer cells also prevent the osteoblasts (OB) from depositing bone.  We have found that metastatic breast cancer cell (BCC) conditioned medium prevents MC3T3-E1 OB differentiation, while causing an increase in the production of inflammatory cytokines. We hypothesize that BCC contact with the OBs, not just the BCC conditioned medium, is important for the cancer cell-OB interaction. Recently, our laboratory has examined the co-culture of cancer cells with MC3T3-E1 OBs using GFP expressing metastatic breast cancer cells (MDA-MB-231-GFP). We found that BCCs attached to OBs within minutes and colonized the OBs regardless of their stage of differentiation. They also brought about an increase in inflammatory cytokines of the type known to recruit and activate osteoclasts. In addition, BCCs caused distinct morphological changes in more immature OBs.  To more closely examine the physical interaction of metastatic BCCs with OBs, we are carryinng out transmission electron microscopy (TEM). However, the GFP fluorescence does not survive the fixation; and it is difficult to distinguish the cancer cells from the OBs. To overcome this problem, we labeled MDA-MB-231-GFP cells with Quantum dots (Qtracker 655™, Invitrogen-Molecular Probes, Qdots), which are photostable fluorophores (20nm in size), which allow for live cell imaging over time at 655nm (Red). In addition, because of their cadmium core, they are electron dense. We monitored Qdot labeled MDA- MB-231-GFP cells for up to 11 days in culture and saw no significant decrease in the intensity of the fluorescence or effects on cell viability. At one hour, Qdots were localized at the plasma membrane, but by 24 hours they were seen in perinuclear vacuoles, where they remained.  By TEM, BCCs could be readily distinguished from the OBs through the presence of the Qdots. At the point of OB-cancer cell interaction, the OBs had a thickened membrane and protrusions containing microtubules. The collagen immediately surrounding the cancer cells was aligned differently from that further away. Moreover, the area adjacent to the leading edge of the cancer cell was devoid of collagen. These studies have shown that BCCs interact with OBs via direct cell-cell contact. Qdots are a useful tool that has allowed us to label and identify breast cancer cells in a co-culture system and will help to further define the interaction of BCCs with OBs.  Huck Institute Innovation Group; The Penn State Cancer Institute, NFCR Center, US Army Medical Research and Materiel Command W81XWH-06-1-0432, Susan G. Koman Breast Cancer Foundation BCTR104406.
P3.13-08 Assessment of EGFR Gene Mutations In cf-DNA in Monitoring of Response to EGFR TKIs in Patients with Lung Adenocarcinoma
Authors: M. Nicoś, K. Wojas-Krawczyk, P. Krawczyk, I. Chmielewska, M. Wojcik-Superczynska, K. Reszka, R. Kieszko, A. Gora-Florek, M. Dudek, D. Swiniuch, W. Papiewski, P. Calka, M. Ciesielka, R. Ramlau, J. Milanowski
Journal: Journal of Thoracic Oncology (2018)
Lesion detection by ceCT, 89Zr-girentuximab and FDG PET/CT in newly diagnosed patients (pts) with metastatic clear cell renal cell carcinoma (mccRCC)
Authors: S.R. Verhoeff, S. Es, E. Boon, E. van Helden, L. Angus, S. Elias, S. Oosting, E. Aarntzen, A. Brouwers, S. Heskamp, O.S. Hoekstra, H.M. Verheul, A.A.M. Van der Veldt, E.G.E. de Vries, O. Boerman, W.T.A. van der Graaf, W.J.G. Oyen, C.M.L. van Herpen
Journal: Annals of Oncology (2018)
Abstract MP010: A Prospective Study of DNA Methylation Age Acceleration and Incidence of Coronary Heart Disease, Heart Failure, and Peripheral Arterial Disease in the Atherosclerosis Risk in Communities (ARIC) Study
Authors: Nicholas Roetker, James Pankow, Jan Bressler, Alanna Morrison, Eric Boerwinkle
Journal: Circulation (2017)

Introduction: DNA methylation patterns used to characterize rate of aging (i.e., epigenetic age acceleration) predict all-cause mortality independently of chronological age and traditional risk factors. It remains unclear how epigenetic age acceleration is associated with cardiovascular disease risk and subclinical atherosclerosis. Hypothesis: Higher epigenetic age acceleration is associated prospectively with greater risk of coronary heart disease (CHD), heart failure (HF), and peripheral arterial disease (PAD) and cross-sectionally with higher carotid intima-medial thickness (IMT). Methods: Age acceleration of blood was estimated by two published methods (Horvath and Hannum) using DNA methylation levels (Illumina 450K array) at 353 and 71 CpG sites in African Americans of the Atherosclerosis Risk in Communities study in 1990-95 (baseline). Among those without prevalent disease at baseline, Cox and linear regression models were used to estimate the association of age acceleration with incident cardiovascular events occurring through 2013 and with carotid IMT cross-sectionally at baseline. Results were stratified by follow-up time for HF due to violation of the proportional hazards assumption. Results: Participants [mean baseline age: 57 years (range: 47-72)] were followed prospectively for a mean 17 years. In fully-adjusted models (Figure), a 1 SD increment in Hannum epigenetic age acceleration was associated with 15-31% greater hazard of incident cardiovascular outcomes, except for HF in later follow-up. Associations using Horvath age acceleration were similar, except it was not associated with myocardial infarction. Cross-sectionally, a 1 SD increment in each age acceleration measure was associated with 0.01 higher baseline carotid IMT (both P ≤ 0.01). Conclusion: This study of African Americans provides evidence that epigenetic age acceleration is associated with greater risk of CHD, HF, and PAD events and higher extent of carotid atherosclerosis, independently of traditional risk factors.
GW29-e0461 Selenium alleviates Endoplasmic Reticulum Stress-induced myocardial fibrosis in mice with alcoholic cardiomyopathy by inhibiting ROS- TGFβ1 pathway
Authors: Suqin Wang, Fang Yuan, Hongzhi Liu, Yanhe Zhu, Chuanyu Gao
Journal: Journal of the American College of Cardiology (2018)
Tumor necrosis factor-α inhibitors for the treatment of pyoderma gangrenosum not associated with inflammatory bowel diseases: A multicenter retrospective study
Authors: Laurie Rousset, Adèle de Masson, Edouard Begon, Axel Villani, Maxime Battistella, Michel Rybojad, Marie Jachiet, Martine Bagot, Jean-David Bouaziz, Clémence Lepelletier
Journal: Journal of the American Academy of Dermatology (2018)
Ixekizumab efficacy and safety in moderate-to-severe genital psoriasis
Authors: C. Ryan, A. Menter, L. Guenther, A. Blauvelt, R. Bissonnette, K. Meeuwis, J. Sullivan, J.C. Cather, G. Yosipovitch, A.B. Gottlieb, J.F. Merola, K. Callis Duffin, S. Fretzin, O.O. Osuntokun, R. Burge, A.N. Naegeli, F.E. Yang, C.-Y. Lin, K. Todd, A. Potts Bleakman
Journal: British Journal of Dermatology (2018)

Psoriasis is a common skin disease that affects about 2% of people worldwide. It presents with red, scaly, and often itchy patches that can affect skin anywhere on the body. About 63% of patients have psoriasis in the genital region at some point in the course of their disease. Genital psoriasis is difficult to treat and it can be a particularly painful, itchy, uncomfortable, and embarrassing form of psoriasis. It also leads to difficulties in personal relationships, sexual health, and overall quality of life. This study aimed to determine whether ixekizumab, a drug used to treat overall psoriasis, also successfully treats genital psoriasis. Patients with genital psoriasis from multiple global countries were treated with either ixekizumab or a placebo (a dummy injection lacking an active drug). The effect of ixekizumab was compared to placebo over 12 weeks of treatment using a combination of clinical tools to measure genital psoriasis severity as well as patient‐completed questionnaires about the impact of their genital psoriasis on their quality of life and sexual health. Ixekizumab provided greater improvements in genital psoriasis severity, with over 73% of patients having minimal or no genital psoriasis and 56% having no genital psoriasis at Week 12. The effect of ixekizumab was rapid, with clear improvements observed as early as the first week of treatment. Rapid and greater improvements were also seen in the severity of genital itching and the impact of genital psoriasis on the frequency of sexual activity. This study suggests that ixekizumab is an effective treatment for genital psoriasis.
A highly collateralized thalamic cell type with arousal-predicting activity serves as a key hub for graded state transitions in the forebrain
Authors: Ferenc Mátyás, Gergely Komlósi, Ákos Babiczky, Kinga Kocsis, Péter Barthó, Boglárka Barsy, Csaba Dávid, Vivien Kanti, Cesar Porrero, Aletta Magyar, Iván Szűcs, Francisco Clasca, László Acsády
Journal: Nature Neuroscience (2018)
GW29-e0469 Critical Appraisal of International Guidelines for the Screening and Treatment of Asymptomatic Coronary Artery Disease: An Issue in Tiny Guidelines Land
Authors: Qinchang Chen, Xiaodong Zhuang, Huimin Zhou, Shaozhao Zhang, Xiuting Sun, Xiangbin Zhong, Zhimin Du, Xinxue Liao
Journal: Journal of the American College of Cardiology (2018)
Radial Fracture Due to Parathyroid Carcinoma
Authors: Taku Suzuki, Yumi Tomiie
Journal: New England Journal of Medicine (2018)

A 45-year-old man with primary hyperparathyroidism due to parathyroid carcinoma presented with pain in his left forearm. Imaging revealed a radial fracture and a diffusely low-density, mottled appearance of the radius and ulna.
Extraintestinal translocation of microbes and tissue specificity in rheumatic musculoskeletal disease (RMD): its more than a gut feeling
Authors: Timothy R D J Radstake
Journal: Annals of the Rheumatic Diseases (2018)

Millions of micro-organisms populate our orifices from the moment we are born until we die. The microbiome represents the totality of micro-organisms that coexist with us rather peacefully and which we acquire purposefully from our environment. Health is associated with a balance between commensal and pathogenic microbes, which control the intestinal barrier integrity through the production of mucus and lipid metabolites, such as short-chain fatty acids. In the case of a disbalance (dysbiosis), leakage of these microbial products negatively affects the immune system, thereby contributing to a chronic proinflammatory state or worse, cancer. Accumulating evidence implicates the microbiota to a plethora of diseases among which rheumatological musculoskeletal disease (RMD).

For instance, the idea that the microbiota is associated with the development of rheumatoid arthritis (RA) has been put forward by several investigators, many of those who have sought the link to intestinal microbes.1–3 On a different take, the oral microbiota, more specifically the presence of Porphyromonas gingivalis , in patients with RA with accompanying periodontitis has been linked to the presence of anticitrullinated protein antibodies.4 In addition, dendritic cells from patients with RA were reported to have a blunted response towards Porphyromonas gingivalis further supporting the notion of an altered systemic immune response to microbiota in RA.5 More recently, the proposed relation between the microbiota and RMD has been extended to systemic sclerosis (SSc) and primary Sjogrens syndrome (pSS).6 7 

Hitherto, all these …
Abstract 15384: Laminar Flow Regulates Endothelial Cell Metabolism via Long Non-coding RNA lncflow2 <i>(Best of Basic Science Abstract)</i>
Authors: Larissa Pfisterer, Teresa Hartung, Katharina M Michalik, Wei Chen, Andreas M Zeiher, Reinier A Boon, Stefanie Dimmeler
Journal: Circulation (2015)

Considering that the transcriptome consists largely of non-coding transcripts, we analysed the impact of atheroprotective laminar flow (20 dynes/cm2) on the expression of long non-coding RNAs (lncRNA) in human endothelial cells (EC) by RNA deep sequencing. Among the significantly up-regulated lncRNAs, we specifically confirmed the up-regulation of lncflow2 upon laminar flow (3.4±1.5, p&lt;0.05) and by overexpressing the flow-induced transcription factor KLF2 (1.95+0.2, p&lt;0.05) by qRT-PCR. Lncflow2 is preferentially localized to the nucleus and RNA immunoprecipitation data indicate an association with the chromatin mark H3K27me3 suggesting that lncflow2 might epigenetically control gene expression. Functionally, the reduction of lncflow2 using LNA-Gapmers suppressed spheroid sprout formation of ECs (34.7 % reduction, p&lt;0.05) and increased expression of endothelial adhesion molecules suggesting that lncflow2 improves EC function and reduces endothelial inflammation. Furthermore, gene ontology analysis of exon microarray analysis with RNA of lncflow2-silenced ECs revealed a significant regulation of metabolic pathways, such as the mevalonate pathway, indicated by elevated acetyl-CoA-acetyltransferase-2, HMG-CoA-reductase and HMG-CoA-synthase-1 expression (confirmed by RT-PCR; all p&lt;0.05). In this context, inhibition of the HMG-Co-reductase by atorvastatin rescued the diminished spheroid sprouting upon loss of lncflow2. To elucidate additional effects on endothelial metabolic function, a mass spectrometry metabolome screening revealed significant alterations in amino acid, glucose and lipid metabolism. Seahorse analysis confirmed these data showing an elevated respiration and fatty acid oxidation in lncflow2 silenced ECs. Our data identify lncflow2 as a flow-regulated lncRNA that modifies EC metabolic responses by controlling metabolism-associated genes- particularly of the mevalonate pathway. Thereby, lncflow2 critically modifies EC functions and may play a regulating role in cellular metabolic adaption to stressors.
FIGO position paper: how to stop the caesarean section epidemic
Authors: Gerard H A Visser, Diogo Ayres-de-Campos, Eytan R Barnea, Luc de Bernis, Gian Carlo Di Renzo, Maria Fernanda Escobar Vidarte, Isabel Lloyd, Anwar H Nassar, Wanda Nicholson, P K Shah, William Stones, Luming Sun, Gerhard B Theron, Salimah Walani
Journal: The Lancet (2018)
Mitochondrial apoptosis is induced by Alkoxy phenyl-1-propanone derivatives through PP2A-mediated dephosphorylation of Bad and Foxo3A in CLL
Authors: Mario Angelo Pagano, Elena Tibaldi, Pierfrancesco Molino, Federica Frezzato, Valentina Trimarco, Monica Facco, Giuseppe Zagotto, Giovanni Ribaudo, Luigi Leanza, Roberta Peruzzo, Ildikò Szabò, Andrea Visentin, Martina Frasson, Gianpietro Semenzato, Livio Trentin, Anna Maria Brunati
Journal: Leukemia (2018)
Abstract 15945: A Novel Defibrillation Tool: Percutaneously Delivered, Partially-insulated Epicardial Defibrillation
Authors: Ammar Killu, Niyada Naksuk, Christopher DeSimone, Faisal Syed, Prakriti Gaba, Dorothy Ladewig, Joanne Powers, Scott Suddendorf, David O Hodge, Gaurav Satam, Michal Crha, Martin Pesl, Frantisek Lehar, Jiri Wolf, Pavel Leinveber, Miroslav Novak, Zdenek Starek, Tomas Kara, Charles Bruce, Paul Friedman, Samuel Asirvatham
Journal: Circulation (2016)

Introduction: Epicardial defibrillator systems typically require surgical access for implantation. Hypothesis: To develop an entirely percutaneous defibrillator system with partially insulated epic...
Evidence for a CD38+ active subset enriched in proliferating cells, within the clonal population in chronic lymphocytic leukemia patients
Authors: Rajendra Damle, Sonal Temburni, Taraneh Banapour, Steven Allen, Kanti Rai, Nicholas Chiorazzi
Journal: Cancer Research (2007)

LB-340  Historically, chronic lymphocytic leukemia (B-CLL) is known as a lymphoid neoplasm characterized by the accumulation of CD5+ B cells showing morphologic features of resting cells. In the last decade several studies have revealed the existence of at least two clinically distinct subgroups among B-CLL cases. These cases can be distinguished by the existence of somatic mutations in Ig V genes and by their expression of cell activation markers such as CD38 and ZAP-70, which have now achieved prognostic significance. To assess which aspects of the immunobiology of B-CLL cells are impacted by expression of CD38 by clonal members within a B-CLL case we flow-sorted B-CLL cells from peripheral blood of 20 patients (% CD38 expression pre-sort, ranging from 1- 90%), into CD38- and CD38+ subsets and quantified telomere lengths as a measure of their replicative history. As a measure of cellular activation we studied telomerase activity in these flow-sorted cells. In addition, expression of activation-associated (CD27, CD69 and CD62L), signaling-associated (ZAP-70) and cell cycle-associated (Ki-67) markers were studied on CD38- and CD38+ cell subsets by immunofluorecence and multi-color flow cytometry in 95 cases (including those used for cell sorting experiments). Telomerase activity was markedly higher in the CD38+ subset compared to the CD38- subset in each case (p