tbuckley/cabot-search huggingface dataset:
Sex Differences in Cardiovascular Pathophysiology
Authors: Anna L. Beale, Philippe Meyer, Thomas H. Marwick, Carolyn S.P. Lam, David M. Kaye
Journal: Circulation (2018)

Consistent epidemiological data demonstrate that patients with heart failure with preserved ejection fraction (HFpEF) are more likely to be women than men. Exploring mechanisms behind this sex difference in heart failure epidemiology may enrich the understanding of underlying HFpEF pathophysiology and phenotypes, with the ultimate goal of identifying therapeutic approaches for the broader HFpEF population. In this review we evaluate the influence of sex on the key domains of cardiac structure and function, the systemic and pulmonary circulation, as well as extracardiac factors and comorbidities that may explain the predisposition of women to HFpEF. We highlight the potential role of factors exclusive to or more prevalent in women such as pregnancy, preeclampsia, and iron deficiency. Finally, we discuss existing controversies and gaps in knowledge, as well as the clinical importance of known sex differences in the context of the potential need for sex-specific diagnostic criteria, improved risk stratification models, and targeted therapies.
When fats commit crimes: fatty acid metabolism, cancer stemness and therapeutic resistance
Authors: Ching‐Ying Kuo, David K. Ann
Journal: Cancer Communications (2018)

Abstract The role of fatty acid metabolism, including both anabolic and catabolic reactions in cancer has gained increasing attention in recent years. Many studies have shown that aberrant expression of the genes involved in fatty acid synthesis or fatty acid oxidation correlate with malignant phenotypes including metastasis, therapeutic resistance and relapse. Such phenotypes are also strongly associated with the presence of a small percentage of unique cells among the total tumor cell population. This distinct group of cells may have the ability to self‐renew and propagate or may be able to develop resistance to cancer therapies independent of genetic alterations. Therefore, these cells are referred to as cancer stem cells/tumor‐initiating cells/drug‐tolerant persisters, which are often refractory to cancer treatment and difficult to target. Moreover, interconversion between cancer cells and cancer stem cells/tumor‐initiating cells/drug‐tolerant persisters may occur and makes treatment even more challenging. This review highlights recent findings on the relationship between fatty acid metabolism, cancer stemness and therapeutic resistance and prompts discussion about the potential mechanisms by which fatty acid metabolism regulates the fate of cancer cells and therapeutic resistance.
DIGITAL CHOLANGIOPANCREATOSCOPY: THE DIAGNOSTIC YIELD AND IMPACT ON MANAGEMENT OF PATIENTS WITH INDETERMINATE BILIARY AND PANCREATIC LESIONS
Authors: O Urban, E Skanderova, P Fojtik, V Zoundjiekpon, M Loveček, P Falt
Journal: Endoscopy (2018)

Single operator cholangiopancreatoscopy (SOC) is an adjunct to endoscopic retrograde cholangiopancreatography used either for diagnostics of ductal lesions or navigated intraductal therapy. The purpose of this study is to evaluate operating characteristics and impact on management of patients with indeterminate biliary and pancreatic lesions.
Oral fingolimod for chronic inflammatory demyelinating polyradiculoneuropathy (FORCIDP Trial): a double-blind, multicentre, randomised controlled trial
Authors: Richard Hughes, Marinos C Dalakas, Ingemar Merkies, Norman Latov, Jean-Marc Léger, Eduardo Nobile-Orazio, Gen Sobue, Angela Genge, David Cornblath, Martin Merschhemke, Carolyn Marie Ervin, Catherine Agoropoulou, Hans-Peter Hartung, Timothy Day, Judith Spies, Leslie Roberts, Philip Van Damme, Peter YK Van den Bergh, Alain Maertens de Noordhout, Annie Dionne, Sandrine Larue, Rami Massie, Michel Melanson, William Camu, Jérôme De Seze, Gwendal Le Masson, Jean Pouget, Jens Schmidt, Vasilios K Kimiskidis, Joab Chapman, Vivian E Drory, Raffaella Fazio, Francesca Gallia, Susumu Kusunoki, Masahiro Mori, Masahiro Iijima, Tomoko Okamoto, Masayuki Baba, Catharina G Faber, Ivo N van Schaik, Waldemar Fryze, Ewa Motta, Krzysztof Selmaj, Carlos Casasnovas, Antonio Guerrero Sola, Isabel Illa, James Holt, James AL Miller, Michael P Lunn, Thomas H Brannagan, Martin Brown, John Kelemen, Stanley Iyadurai, Kourosh Rezania, Khema R Sharma, Rup Tandan, Mark Gudesblatt, Victoria Lawson, Anthony A Amato
Journal: The Lancet Neurology (2018)
A PROSPECTIVE STUDY TO ASSESS SAFETY AND EFFICACY OF USING AIR CHOLANGIOGRAPHY IN PATIENTS WITH HILAR STRICTURES, CHOLANGIOCARCINOMA IN CHD SECONDARY TO CARCINOMA GALL BLADDER
Authors: Z Pradeep Sharma, R Pradeep Sharma
Journal: Endoscopy (2018)

A prospective study to assess the safety and efficacy of using air for cholangiography in patients with hilar strictures, high cholangio carcinoma in CHD and CHD strictures secondary to carcinoma gall bladder.
Splicing heterogeneity: separating signal from noise
Authors: Yihan Wan, Daniel R. Larson
Journal: Genome biology (2018)

Single-cell analyses have revealed a tremendous variety among cells in the abundance and chemical composition of RNA. Much of this heterogeneity is due to alternative splicing by the spliceosome. Little is known about how many of the resulting isoforms are biologically functional or just provide noise with little to no impact. The dynamic nature of the spliceosome provides numerous opportunities for regulation but is also the source of stochastic fluctuations. We discuss possible origins of splicing stochasticity, the experimental approaches for studying heterogeneity in isoforms, and the potential biological significance of noisy splicing in development and disease.
Delivery Strategies for Immune Checkpoint Blockade
Authors: Qian Chen, Chao Wang, Guojun Chen, Quanyin Hu, Zhen Gu
Journal: Advanced Healthcare Materials (2018)

Immune checkpoint blockade, which blocks the regulatory pathways that express on immune cells to improve antitumor immunological responses, is becoming one of the most promising approaches for antitumor therapy. This therapy has achieved important clinical advancement and provided a new opportunity against a variety of cancers. However, limitations of checkpoint inhibitors application, including the risk of autoimmune disease, low objective response rates, and high cost, still largely affect their broad applications in patients. Therefore, it is desirable to seek effective delivery methods to further enhance the therapeutic efficacy and reduce drawbacks of immune checkpoint blockade. This brief review summarizes strategies to increase the antitumor immunity, including the local and targeted delivery of checkpoint inhibitors, and a combination of different checkpoint inhibitors or with other therapeutic treatments.
New Surviving Sepsis Campaign guidelines: back to the art of medicine
Authors: Raffaele Scala, Marcus Schultz, Lieuwe D.J. Bos, Antonio Artigas
Journal: European Respiratory Journal (2018)

<b>Surviving Sepsis Campaign guidelines represent an advanced step in the implementation of precision medicine in this field of respiratory and intensive care medicine, where evidence-based recommendations are integrated with best-practice suggestions</b>http://ow.ly/hlk230ko1GN
Erbin Suppresses KSR1-Mediated RAS/RAF Signaling and Tumorigenesis in Colorectal Cancer
Authors: Payton D. Stevens, Yang-An Wen, Xiaopeng Xiong, Yekaterina Y. Zaytseva, Austin T. Li, Chi Wang, Ashley T. Stevens, Trevor N. Farmer, Tong Gan, Heidi L. Weiss, Masaki Inagaki, Sylvie Marchetto, Jean-Paul Borg, Tianyan Gao
Journal: Cancer Research (2018)

Erbin belongs to the LAP (leucine-rich repeat and PDZ domain) family of scaffolding proteins that plays important roles in orchestrating cell signaling. Here, we show that Erbin functions as a tumor suppressor in colorectal cancer. Analysis of Erbin expression in colorectal cancer patient specimens revealed that Erbin was downregulated at both mRNA and protein levels in tumor tissues. Knockdown of Erbin disrupted epithelial cell polarity and increased cell proliferation in 3D culture. In addition, silencing Erbin resulted in increased amplitude and duration of signaling through Akt and RAS/RAF pathways. Erbin loss induced epithelial-mesenchymal transition, which coincided with a significant increase in cell migration and invasion. Erbin interacted with kinase suppressor of Ras 1 (KSR1) and displaced it from the RAF/MEK/ERK complex to prevent signal propagation. Furthermore, genetic deletion of Erbin in Apc knockout mice promoted tumorigenesis and significantly reduced survival. Tumor organoids derived from Erbin/Apc double knockout mice displayed increased tumor initiation potential and activation of Wnt signaling. Results from gene set enrichment analysis revealed that Erbin expression associated positively with the E-cadherin adherens junction pathway and negatively with Wnt signaling in human colorectal cancer. Taken together, our study identifies Erbin as a negative regulator of tumor initiation and progression by suppressing Akt and RAS/RAF signaling in vivoSignificance: These findings establish the scaffold protein Erbin as a negative regulator of EMT and tumorigenesis in colorectal cancer through direct suppression of Akt and RAS/RAF signaling. Cancer Res; 78(17); 4839-52. ©2018 AACR.
The Obesity Paradigm and Lifetime Risk of Cardiovascular Disease
Authors: Salvatore Carbone, Carl J. Lavie, Ross Arena
Journal: JAMA Cardiology (2018)

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 Cardiology 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 Cardiology journal
Pharmacokinetics and biodistribution of polymeric micelles containing miRNA and small-molecule drug in orthotopic pancreatic tumor-bearing mice
Authors: Virender Kumar, Vaibhav Mundra, Yang Peng, Yingzhe Wang, Chalet Tan, Ram I Mahato
Journal: Theranostics (2018)

Rationale: Successful treatment of pancreatic cancer remains a challenge due to desmoplasia and prevalence of KRAS mutation. While hedgehog (Hh) ligand levels are upregulated in pancreatic cancer cells and contribute to desmoplasia, there is significant downregulation of tumor suppressor let-7b, which targets mutant KRAS, C-MYC and several other genes involved in pancreatic cancer progression, invasion, and metastasis. We recently explored combination therapy of GDC-0449 (Hh inhibitor) and let-7b mimic using poly(ethylene glycol)-block-poly(2-methyl-2-carboxyl-propylene carbonate-graft-dodecanol-graft-tetraethylenepentamine) (PEG-b-PCC-g-DC-g-TEPA) micelles in pancreatic tumor mouse model. Here, our objective was to determine the biodistribution (BD), pharmacokinetics (PK), therapeutic efficacy and toxicity of this micellar formulation. Methods: We determined the PK of micelles encapsulating Cy5.5-let-7b and GDC-0449 following intravenous injection in orthotopic pancreatic tumor-bearing NSG mice at doses of 2 mg/kg and 10 mg/kg, respectively. Mice were scanned for fluorescence by IVIS to determine the biodistribution of Cy5.5-let-7b at the whole-body level, and its concentration in plasma and major organs was determined by measuring fluorescence using a fluorimeter and by real-time RT-PCR. GDC-0449 concentration was determined by LC/MS/MS. Therapeutic efficacy and toxicity of the micellar formulation of let-7b and GDC-0449 was also determined after two weeks of treatment. Results: The use of a micellar formulation markedly prolonged the elimination half-life (t1/2, e) of Cy5.5-let-7b in plasma from 0.49 ± 0.19 h to 2.65 ± 0.46 h and increased the area-under-the-curve (AUC 0-∞ ) by 7-fold, while t1/2,e and AUC 0-∞ of GDC-0449 were increased by 1.78-fold and 3.2-fold, respectively. The micelles significantly decreased the clearance of both encapsulated let-7b mimic and GDC-0449 compared to the emulsion formulation. Compared to the emulsion counterpart, the micellar formulation elevated the delivery of Cy5.5-let-7b and GDC-0449 to the orthotopic pancreatic tumor tissue by 7.8- and 4.2-fold, respectively. Furthermore, there was a significant reduction in tumor volume and negligible systemic toxicity as evident by hematological parameters and histological evaluation. Conclusion: PEG-b-PCC-g-DC-g-TEPA micelles carrying GDC-0449 and let-7b mimic have great potential to improve drug delivery for pancreatic cancer treatment.
Abstract 9577: 25-year Trends In First-time Hospitalization For Acute Myocardial Infarction, Subsequent Short- And Long-term Mortality, And The Prognostic Impact Of Gender And Comorbidity: A Danish Nationwide Cohort Study
Authors: Morten Schmidt, Jacob Jacobsen, Timothy L Lash, Hans E Bøtker, Henrik T Sørensen
Journal: Circulation (2011)

Background: A marked decrease in incidence of acute myocardial infarction and associated mortality has occurred since 1980. No studies have reported on 25-year trends in a nationwide unselected population. We examined 25-year trends in first-time hospitalization for acute myocardial infarction in Denmark, subsequent short- and long-term mortality, and the prognostic impact of gender and comorbidity. Methods: We conducted this nationwide population-based cohort study using medical registries. We identified all 234,331 patients with a first-time hospitalization for myocardial infarction from 1984 through 2008. We calculated the standardized incidence rate of myocardial infarction and 30-day and 31-365-day mortality by gender. We defined no, low, moderate, and high comorbidity levels according to the Charlson Comorbidity Index. We used Cox regression to compute mortality rate ratios comparing comorbidity categories. Results: The standardized incidence rate per 100,000 persons decreased in the 25-year period by 37% for women (from 209 to 131) and by 48% for men (from 410 to 213). The 30-day mortality declined from 31.4% in 1984-1988 to 14.8% in 2004-2008. The 31-365-day mortality declined from 15.6% in 1984-1988 to 11.1% in 2004-2008. After adjustment for age at time of myocardial infarction, men and women had the same one-year risk of dying. The mortality reduction was independent of comorbidity level. Comparing patients with high and with no comorbidity during 2004-2008, the mortality rate ratio, adjusted for age and gender, was 1.96 (95% confidence interval: 1.83 to 2.11) within 30 days and 3.89 (95% confidence interval: 3.58 to 4.24) between 31 and 365 days. Conclusion: The rate of first-time hospitalization for myocardial infarction and subsequent short-term mortality both declined by nearly half between 1984 and 2008. The reduction in mortality occurred for all patients, independent of gender and comorbidity. However, comorbidity burden was a strong prognostic factor for short and long-term mortality, while gender was not.
Synovial macrophage M1 polarisation exacerbates experimental osteoarthritis partially through R-spondin-2
Authors: Haiyan Zhang, Chuangxin Lin, Chun Zeng, Zhenyu Wang, Hua Wang, Jiansen Lu, Xin Liu, Yan Shao, Chang Zhao, Jianying Pan, Song Xu, Yue Zhang, Denghui Xie, Daozhang Cai, Xiaochun Bai
Journal: Annals of the Rheumatic Diseases (2018)

Objectives To investigate the roles and regulatory mechanisms of synovial macrophages and their polarisation in the development of osteoarthritis (OA). Methods Synovial tissues from normal patients and patients with OA were collected. M1 or M2-polarised macrophages in synovial tissues of patients with OA and OA mice were analysed by immunofluorescence and immunohistochemical staining. Mice with tuberous sclerosis complex 1 (TSC1) or Rheb deletion specifically in the myeloid lineage were generated and subjected to intra-articular injection of collagenase (collagenase-induced osteoarthritis, CIOA) and destabilisation of the medial meniscus (DMM) surgery to induce OA. Cartilage damage and osteophyte size were measured by Osteoarthritis Research Society International score and micro-CT, respectively. mRNA sequencing was performed in M1 and control macrophages. Mice and ATDC5 cells were treated with R-spondin-2 (Rspo2) or anti-Rspo2 to investigate the role of Rspo2 in OA. Results M1 but not M2-polarised macrophages accumulated in human and mouse OA synovial tissue. TSC1 deletion in the myeloid lineage constitutively activated mechanistic target of rapamycin complex 1 (mTORC1), increased M1 polarisation in synovial macrophages and exacerbated experimental OA in both CIOA and DMM models, while Rheb deletion inhibited mTORC1, enhanced M2 polarisation and alleviated CIOA in mice. The results show that promoting the macrophage M1 polarisation leads to exacerbation of experimental OA partially through secretion of Rspo2 and activation of β-catenin signalling in chondrocytes. Conclusions Synovial macrophage M1 polarisation exacerbates experimental CIOA partially through Rspo2. M1 macrophages and Rspo2 are potential therapeutic targets for OA treatment.
Mucin 1 deficiency mediates corticosteroid insensitivity in asthma
Authors: Javier Milara, Anselm Morell, Alfredo de Diego, Enrique Artigues, Esteban Morcillo, Julio Cortijo
Journal: Allergy (2018)

Abstract Background The loss of corticosteroid efficacy is an important issue in severe asthma management and may lead to poor asthma control and deterioration of airflow. Recent data indicate that Mucin 1 ( MUC 1) membrane mucin can mediate corticosteroid efficacy in chronic rhinosinusitis, but the role of MUC 1 in uncontrolled severe asthma is unknown. The objective was to analyze the previously unexplored role of MUC 1 on corticosteroid efficacy in asthma. Methods Mucin 1 expression was evaluated by real‐time PCR in human bronchial epithelial cells ( HBEC ) and blood neutrophils from uncontrolled severe asthma (n = 27), controlled mild asthma (n = 16), and healthy subjects (n = 13). IL ‐8, MMP 9, and GM ‐ CSF were measured by ELISA in HBEC and neutrophils. An asthma model of ovalbumin ( OVA ) was used in MUC 1 KO and WT C57 BL /6 mice according to ARRIVE guidelines. Results Mucin 1‐ CT expression was downregulated in bronchial epithelial cells and peripheral blood neutrophils from severe asthma patients compared with mild asthma and healthy subjects ( P &lt; 0.05). Daily dose of inhaled corticosteroids ( ICS ) inversely correlated with MUC 1 expression in neutrophils from mild and severe asthma (ρ = −0.71; P &lt; 0.0001). Dexamethasone showed lower anti‐inflammatory effects in severe asthma peripheral blood neutrophils and HBEC s stimulated with lipopolysaccharide ( LPS ) than in cells from mild asthma. Glucocorticoid receptor ( GR )‐α phosphorylated at serine 226 was increased in cells from severe asthma, and the MUC 1‐ CT / GR α complex was downregulated in severe asthma cells. OVA asthma model in MUC 1 KO mice was resistant to the anti‐inflammatory effects of dexamethasone. Conclusion Mucin 1‐ CT modulates corticosteroid efficacy in vitro and in vivo asthma models.
Lesson of the week: cyclosporin treatment for ulcerative colitis complicated by fatal pneumocystis carinii pneumonia
Authors: V. A Quan, B. P Saunders, B. H Hicks, G. E Sladen
Journal: BMJ (1997)

Iron deficiency is the commonest cause of anaemia worldwide and is frequently seen in general practice.The anaemia of iron deficiency is caused by defective synthesis of haemoglobin, resulting in red cells that are smaller than normal (microcytic) and contain reduced amounts of haemoglobin (hypochromic). Iron metabolismIron has a pivotal role in many metabolic processes, and the average adult contains 3-5 g of iron, of which two thirds is in the oxygen-carrying molecule haemoglobin.A normal Western diet provides about 15 mg of iron daily, of which 5-10% is absorbed, principally in the duodenum and upper jejunum, where the acidic conditions help the absorption of iron in the ferrous form.Absorption is helped by the presence of other reducing substances, such as hydrochloric acid and ascorbic acid.The body has the capacity to increase its iron absorption in the face of increased demand-for example, in pregnancy, lactation, growth spurts, and iron deficiency.Once absorbed from the bowel, iron is transported across the mucosal cell to the blood, where it is carried by the protein transferrin to developing red cells in the bone marrow.Iron stores comprise ferritin, a labile and readily accessible source of iron, and haemosiderin, an insoluble form found predominantly in macrophages.About 1 mg of iron a day is shed from the body in urine, faeces, sweat, and cells shed from the skin and gastrointestinal tract.Menstrual losses of an additional 20 mg a month and the increased requirements of pregnancy (500-1000 mg) contribute to the higher incidence of iron deficiency in women of reproductive age.
The Amino Acid Composition of Hemoglobin. V. The Preparation of Purified Hemoglobin Fractions by Chromatography on Cellulose Exchangers and Their Identification by Starch Gel Electrophoresis Using Tris-Borate-EDTA Buffer
Authors: AMOZ I. CHERNOFF, NELSON PETTIT, JO NORTHROP
Journal: Blood (1965)
Assessment of Lung Cancer Risk on the Basis of a Biomarker Panel of Circulating Proteins
Authors: Florence Guida, Nan Sun, Leonidas E. Bantis, David C. Muller, Peng Li, Ayumu Taguchi, Dilsher Dhillon, Deepali L. Kundnani, Nikul J. Patel, Qingxiang Yan, Graham Byrnes, Karel G. M. Moons, Anne Tjønneland, Salvatore Panico, Claudia Agnoli, Paolo Vineis, Domenico Palli, Bas Bueno-de-Mesquita, Petra H. Peeters, Antonio Agudo, Jose M. Huerta, Miren Dorronsoro, Miguel Rodriguez Barranco, Eva Ardanaz, Ruth C. Travis, Karl Smith Byrne, Heiner Boeing, Annika Steffen, Rudolf Kaaks, Anika Hüsing, Antonia Trichopoulou, Pagona Lagiou, Carlo La Vecchia, Gianluca Severi, Marie-Christine Boutron-Ruault, Torkjel M. Sandanger, Elisabete Weiderpass, Therese H. Nøst, Kostas Tsilidis, Elio Riboli, Kjell Grankvist, Mikael Johansson, Gary E. Goodman, Ziding Feng, Paul Brennan, Mattias Johansson, Samir M. Hanash
Journal: JAMA Oncology (2018)

There is an urgent need to improve lung cancer risk assessment because current screening criteria miss a large proportion of cases.