tbuckley/cabot-search huggingface dataset:
Nephrin Signaling Results in Integrin β1 Activation
Authors: Christopher Philipp Dlugos, Cara Picciotto, Carolin Lepa, Malte Krakow, Antje Stöber, Mee-Ling Eddy, Thomas Weide, Astrid Jeibmann, Michael P. Krahn, Veerle Van Marck, Jürgen Klingauf, Andrea Ricker, Roland Wedlich-Söldner, Hermann Pavenstädt, Christian Klämbt, Britta George
Journal: Journal of the American Society of Nephrology (2019)

Significance Statement The slit diaphragm protein Nephrin, which is essential for an intact glomerular filter, signals from the podocyte slit diaphragm to the Actin cytoskeleton and induces lamellipodia formation. The authors present evidence that Nephrin activation results in activation of Integrin β 1 in a cultured human podocyte model, and that C3G, a guanine nucleotide exchange factor of the small GTPase Rap1, is involved in Nephrin signaling to Integrin β 1. In vivo , in Drosophila nephrocytes, the Nephrin ortholog Sticks and stones is necessary for correct targeting of Integrin β 1. These findings indicate that Nephrin can mediate a signaling pathway that results in activation of Integrin β 1 at focal adhesions, which may affect podocyte attachment to the extracellular matrix. Background Patients with certain mutations in the gene encoding the slit diaphragm protein Nephrin fail to develop functional slit diaphragms and display severe proteinuria. Many adult-onset glomerulopathies also feature alterations in Nephrin expression and function. Nephrin signals from the podocyte slit diaphragm to the Actin cytoskeleton by recruiting proteins that can interact with C3G, a guanine nucleotide exchange factor of the small GTPase Rap1. Because Rap activity affects formation of focal adhesions, we hypothesized that Nephrin transmits signals to the Integrin receptor complex, which mediates podocyte adhesion to the extracellular matrix. Methods To investigate Nephrin’s role in transmitting signals to the Integrin receptor complex, we conducted genetic studies in Drosophila nephrocytes and validated findings from Drosophila in a cultured human podocyte model. Results Drosophila nephrocytes form a slit diaphragm–like filtration barrier and express the Nephrin ortholog Sticks and stones (Sns). A genetic screen identified c3g as necessary for nephrocyte function. In vivo , nephrocyte-specific gene silencing of sns or c3g compromised nephrocyte filtration and caused nephrocyte diaphragm defects. Nephrocytes with impaired Sns or C3G expression displayed an altered localization of Integrin and the Integrin-associated protein Talin. Furthermore, gene silencing of c3g partly rescued nephrocyte diaphragm defects of an sns overexpression phenotype, pointing to genetic interaction of sns and c3g in nephrocytes. We also found that activated Nephrin recruited phosphorylated C3G and resulted in activation of Integrin β 1 in cultured podocytes. Conclusions Our findings suggest that Nephrin can mediate a signaling pathway that results in activation of Integrin β 1 at focal adhesions, which may affect podocyte attachment to the extracellular matrix.
An injectable implant to stimulate the sphenopalatine ganglion for treatment of acute ischaemic stroke up to 24 h from onset (ImpACT-24B): an international, randomised, double-blind, sham-controlled, pivotal trial
Authors: Natan M Bornstein, Jeffrey L Saver, Hans Christoph Diener, Philip B Gorelick, Ashfaq Shuaib, Yoram Solberg, Lisa Thackeray, Milan Savic, Tamar Janelidze, Natia Zarqua, David Yarnitsky, Carlos A Molina, Ashfaq Shuaib, Michael Hill, Daniel Vaclavik, David Skoloudik, Jan Fiksa, Grethe Andersen, Pekka Jakala, Turgut Tatlisumak, Igor Kuzmanovski, Benoit Guillon, Hugues Chabriat, Marie Helene Mahagne, Serge Timsit, Thomas Ronziere, Gocha Ingorokva, Maya Beridze, Mzia Beridze, Natia Zarqua, Nino Kharaishvili, Nodar Kakabadze, Tamar Janelidze, Bernd Griewing, Carsten Hobohm, Dietmar Schneider, Christian Weimar, Holger Poppert, Hubert Kimmig, Joerg Berrouschot, Peter Ringleb, Stefan Schwab, Martin Kohrmann, Bernd Kallmunzer, Rainer Kollmar, Matthias Endres, Karl-Georg Hausler, Raymond Cheung, Thomas Wai Hong Leung, Elena Dorodnicov, Hen Halevi, Eitan Auriel, Jonathan Streifler, Ronen Leker, Yvonne Schwammenthal, Danilo Toni, Giancarlo Agnelli, Valeria Caso, Agnieszka Słowik, Anna Czlonkowska, Ignacy Lubinski, Jan Kochanowicz, Piotr Sobolewski, Waldemar Brola, Antonio Vasco Salgado, Carlos Correia, Elsa Azevedo, Jose Roriz, Marija Zarkov, Milan Savic, Zarko Petrovic, Georgi Krastev, Miloslav Dvorak, Ana Rodriguez Campello, Antonio Gil Nunez, Carlos Molina, Francisco Purroy, Joan Marti-Fabregas, Juan Arenillas, Maria Alonso, Pedro Cardona, Miguel Blanco Gonzalez, Silvia Tur, Tomas Segura Martin, Payenok Anzhelika, Harish Shownkeen, Mauricio Concha, Pramod Sethi, Souvik Sen, Syed Zaidi, Syed Zaidi, Thomas Devlin
Journal: The Lancet (2019)
Abstract IA10: Deconstructing and reconstructing the ovarian cancer microenvironment
Authors: Frances R. Balkwill
Journal: Clinical Cancer Research (2018)

Abstract The tumor microenvironment (TME) is critical for cancer growth and spread. However, the relationships between molecular components of the TME and higher-order features, tissue stiffness, extent of disease, and cellularity are not known. Using clinical samples of metastatic high-grade serous ovarian cancer (HGSOC) that ranged from minimal to extensive disease, we have defined RNA and protein profiles that evolved with these higher-order features. We obtained a unique profile of the evolving metastatic microenvironment of HGSOC that includes data not only on gene expression and proteomics but also cytokine/chemokine expression, ECM organization, and biophysical properties. This “deconstruction” of a metastatic microenvironment provides a critical reference for our mouse model systems and a template for reconstruction of 3D multicellular human ovarian cancer models as will be detailed in this presentation. Although our work was conducted on omental metastases of HGSOC, we found evidence for a conserved mechanism that may be relevant to many human solid tumors: a pattern of matrix-associated gene expression that we termed the matrix index. In the HGSOC samples, the matrix index significantly associated with various leukocyte signaling pathways of cells associated with poor prognosis including Th2 cells and macrophage-associated genes and correlated with extent of disease and tissue stiffness. Interrogating transcriptional datasets from a wide range of human solid cancers, including HGSOC, we found that the matrix index had prognostic significance irrespective of patient age, stage of disease, or first response to therapy. This led us to suggest that there may be a common matrix response to human cancer. Citation Format: Frances R. Balkwill. Deconstructing and reconstructing the ovarian cancer microenvironment. [abstract]. In: Proceedings of the AACR Conference: Addressing Critical Questions in Ovarian Cancer Research and Treatment; Oct 1-4, 2017; Pittsburgh, PA. Philadelphia (PA): AACR; Clin Cancer Res 2018;24(15_Suppl):Abstract nr IA10.
Abstract 20656: Publication Rates of Abstracts Presented at Major Cardiovascular Subspecialty Conferences
Authors: Brittany Owen, Jason Hoff, David Aguilar, Ali Denktas, Salim Virani, Nasser Lakkis, Biykem Bozkurt, Anita Deswal, Tina Shah, Arunima Misra, Hani Jneid, Christie Ballantyne, Vijay Nambi
Journal: Circulation (2016)

Introduction: Peer review and publication of all research is a vital requirement in science. Scientific meetings aim to educate and introduce new scientific advances. Although abstracts submitted t...
Immune cell trafficking and retention in inflammatory bowel disease: mechanistic insights and therapeutic advances
Authors: Sebastian Zundler, Emily Becker, Lisa Lou Schulze, Markus F Neurath
Journal: Gut (2019)

Intestinal immune cell trafficking has been identified as a central event in the pathogenesis of inflammatory bowel diseases (IBD). Intensive research on different aspects of the immune mechanisms controlling and controlled by T cell trafficking and retention has led to the approval of the anti-α4β7 antibody vedolizumab, the ongoing development of a number of further anti-trafficking agents (ATAs) such as the anti-β7 antibody etrolizumab or the anti-MAdCAM-1 antibody ontamalimab and the identification of potential future targets like G-protein coupled receptor 15. However, several aspects of the biology of immune cell trafficking and regarding the mechanism of action of ATAs are still unclear, for example, which impact these compounds have on the trafficking of non-lymphocyte populations like monocytes and how precisely these therapies differ with regard to their effect on immune cell subpopulations. This review will summarise recent advances of basic science in the field of intestinal immune cell trafficking and discuss these findings with regard to different pharmacological approaches from a translational perspective.
Bone seeking matrix metalloproteinase-2 (MMP-2) inhibitors can prevent bone metastatic breast cancer
Authors: M. Tauro, C.C. Lynch
Journal: Annals of Oncology (2019)

Background: Breast to bone metastasis is a common event during breast cancer progression. The resultant lesions are painful and currently, despite medical advances, are incurable. Therefore, identifying the underpinning molecular mechanisms in the bone microenvironment is vital for the development of new therapies. Gene expression analysis and validation in human and murine specimens of bone metastases revealed matrix metalloproteinases, such as MMP-2, are highly expressed in the bone metastatic microenvironment. These data support the rationale for the development of a highly specific MMP-2 inhibitor for the eradication of active bone metastatic breast cancer. Methods: Given that previous broad-spectrum MMP inhibitor (MMPI) trials were unsuccessful due to dose limiting systemic side effects, we utilized a novel chemical approach to synthesize bone seeking MMP inhibitors (BMMPIs) on a bisphosphonic backbone, with specificity for MMP-2 in the nanomolar range (IC50=140 nM). Based on our previous data about BMMPI's ability to significantly reduce breast cancer growth in the bone microenvironment, we decided to investigate the role of BMMPI such as ML115 in preventing dissemination of cancer cells into the skeleton. Balb-c female mice (n = 10/group), pretreated for 7 days with vehicle, standard of care bisphosphonate (Zoledronate= 1 mg/kg) and BMMPIs (ML115= 1 mg/kg), were randomized and intra-cardiac injected with luciferase expressing 4T1 (2x105) breast cancer cell line. Tumor growth was assessed via luminescence quantitation overtime. Results: Our preliminary total body bioluminescent data suggest that pretreatment with ML115 can significantly reduce the amount of breast cancer cells homing into the bone, compared to vehicle and standard bisphosphonate. Cancer induced bone disease was measured ex vivo by μCT, Xray and histomorphometry. Ex vivo analysis also illustrated the significant beneficial effects of the BMMPIs in reducing the size of osteolytic lesions. We are currently measuring MMP activity in vivo and ex vivo via specific activatable MMP probes, in order to confirm BMMPI mechanism of action. Conclusions: We predict that BMMPIs could be used as preventive treatment to impair breast cancer to bone metastasis in clinic. Legal entity responsible for the study: H Lee Moffitt Cancer Center. Funding: Susan G Komen Breast Cancer Foundation and American Airlines. Disclosure: All authors have declared no conflicts of interest.
New-onset atrial fibrillation in adult critically ill patients: a scoping review
Authors: Mik Wetterslev, Nicolai Haase, Christian Hassager, Emilie P. Belley-Cote, William F. McIntyre, Youzhong An, Jiawei Shen, Alexandre Biasi Cavalcanti, Fernando G. Zampieri, Helio Penna Guimaraes, Anders Granholm, Anders Perner, Morten Hylander Møller
Journal: Intensive Care Medicine (2019)
High Time for Complete Ban on Asbestos Use in Developing Countries
Authors: Tianhui Chen, Xiao-Ming Sun, Licun Wu
Journal: JAMA Oncology (2019)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA Oncology 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 Oncology journal
Apport de la CPRE dans la prise en charge des kystes hydatiques du foie rompus dans les voies biliaires
Authors: S Mrabti, H Seddik, S Berrag, H Boutallaka, S Morabit, A Sair, I El Koti, S Sentissi, A Benkirane
Journal: Endoscopy (2019)

Le kyste hydatique du foie est une affection parasitaire due au développement de la forme larvaire du tænia du chien: Echinococcus Granulosus. La fistulisation dans les voies biliaires est la complication la plus fréquente. Le traitement endoscopique s'impose en raison des risques liés à la chirurgie. L'objectif de notre étude est d'évaluer l'efficacité de la Cholangiopancréatografie rétrograde endoscopique dans la prise en charge des kystes hydatiques du foie rompus dans les voies biliaires.
The “Conscience” Rule: How Will It Affect Patients’ Access to Health Services?
Authors: Lawrence O. Gostin
Journal: JAMA (2019)

On May 2, 2019, the US Department of Health and Human Services (HHS) and Office of Civil Rights (OCR) released a final rule that heightens the rights of hospitals and health workers to refuse to participate in patients’ medical care based on religious or moral grounds. The rule covers OCR’s authority to investigate and enforce violations of 25 federal “conscience protection” laws. Tied to the US Constitution’s spending power, the rule applies to state and local governments, as well as public and private health care professionals and entities if they receive federal funds such as Medicare or Medicaid. The rule applies to a range of important health services such as abortions, sterilizations, assisted suicide, and advance directives — extending to sex reassignment and HIV treatment.
Quantitative CMR population imaging on 20,000 subjects of the UK Biobank imaging study: LV/RV quantification pipeline and its evaluation
Authors: Rahman Attar, Marco Pereañez, Ali Gooya, Xènia Albà, Le Zhang, Milton Hoz de Vila, Aaron M. Lee, Nay Aung, Elena Lukaschuk, Mihir M. Sanghvi, Kenneth Fung, Jose Miguel Paiva, Stefan K. Piechnik, Stefan Neubauer, Steffen E. Petersen, Alejandro F. Frangi
Journal: Medical Image Analysis (2019)
La myotomie per-orale endoscopique pour achalasie: faut-il choisir la voie antérieure ou postérieure? Etude randomisée prospective multicentrique internationale
Authors: M Pioche, J Rivory, S Roman, F Mion, T Ponchon
Journal: Endoscopy (2019)

La myotomie endoscopique perorale (POEM) est une procédure qui a révolutionné le traitement de l'achalasie depuis sa création en 2008. Les POEMs peuvent être effectuées par voie antérieure ou postérieure. L'objectif principal de cette étude était de comparer l'efficacité et la morbidité des approches antérieure et postérieure à 12 mois après la myotomie.
Getting stuck or choosing to stay? Neutrophil transit times in the lung in acute inflammation and COPD
Authors: Elizabeth Sapey, Robert A Stockley
Journal: Thorax (2019)

The neutrophil is generally recognised as a key cellular mediator in the pathophysiology of chronic obstructive pulmonary disease (COPD). This is based on the propensity for the cell to release proinflammatory mediators including superoxide radicals and importantly serine proteinases. These products have been shown to replicate many of the pathological changes typical of COPD in cell-based and animal models1 and have significant potential for bystander tissue damage, especially when the neutrophil is primed or activated and degranulates more readily.2 Further, studies have consistently shown increased numbers of neutrophils, neutrophil-associated cytokines and neutrophil chemoattractants in COPD airway fluids (be they collected as spontaneous3 or induced sputum4 or as bronchoalveolar lavage5) and the numbers of neutrophils and their products correlate with disease severity/activity, as determined by the degree of airway obstruction, decline in FEV1 (Forced Expiratory Volume in 1 Second) or severity of emphysema present.6 Also, neutrophilia in COPD lung secretions is seen regardless of the clinical phenotype; although some phenotypes are associated with a greater burden of neutrophilic inflammation or a reduced capacity for neutrophil proteinase inhibition, including those patients with chronic bronchitis, frequent exacerbators or those colonised with bacteria, as recently reviewed.7 However, this wealth of data supporting neutrophils in COPD pathogenesis is tempered by two potentially conflicting observations. First, histological studies have not reported a neutrophilia within the airway wall in COPD8 and second, neutrophils are avid phagocytes but COPD patients are still commonly colonised with potentially pathogenic bacteria.9 This leads to several key questions. (1) Do neutrophils accumulate in the lungs in COPD? (2) If so, where? (3) Why are they there? (4) Can therapeutics modulate neutrophil accumulation to preserve host health?

The neutrophil is usually considered a transitory rather than tissue resident cell, migrating to areas of …
Cancer prevalence is increased in females with sleep apnoea: data from the ESADA study
Authors: Athanasia Pataka, Maria R. Bonsignore, Silke Ryan, Renata L. Riha, Jean-Louis Pepin, Sofia Schiza, Ozen K. Basoglu, Pawel Sliwinski, Ondrej Ludka, Paschalis Steiropoulos, Ulla Anttalainen, Walter T. McNicholas, Jan Hedner, Ludger Grote
Journal: European Respiratory Journal (2019)

<b>In a cross-sectional analysis of the European Sleep Apnoea Database (ESADA), cancer prevalence was higher in females with OSA and nocturnal hypoxia, but not in males. Further studies are needed to assess causality of gender, OSA and cancer incidence.</b>http://bit.ly/2YuxyZA
ESD WITH DOUBLE CLIP AND RUBBER BAND TRACTION OF NEOPLASTIC LESIONS DEVELOPED IN THE APPENDICEAL ORIFICE IS EFFECTIVE AND SAFE
Authors: B Oung, J Jacques, J Rivory, R Legros, F Rostain, E Chabrun, V Hervieu, M Moreno-Garcia, JC Saurin, T Ponchon, M Pioche
Journal: Endoscopy (2019)

Endoscopic resection of Superficial Colorectal lesions in close proximity to the Appendiceal Orifice (L-PAO) was shown to be feasible but is considered impossible in case of deep invasion into the appendix (type 3). We report here a series of Endoscopic Submucosal Dissection with double clip and rubber band traction (DCT-ESD) of L-PAO to determine the outcomes.
Management of mental health emergencies in elite athletes: a narrative review
Authors: Alan Currie, David McDuff, Allan Johnston, Phil Hopley, Mary E Hitchcock, Claudia L Reardon, Brian Hainline
Journal: British Journal of Sports Medicine (2019)

Mental health emergencies require a rapid, effective response. We searched the literature on mental health emergencies in athletes and found five papers. None of these addressed elite athletes. Nonetheless, common mental health emergencies may present in the sports environment and may place the athlete and others at risk. Sports teams and organisations should anticipate which emergencies are likely and how medical and support staff can best respond. Responses should be based on general non-sporting guidelines. We stress the importance of clinicians following standard procedures.
Reproducibility of Three-Dimensional Vascular Ultrasound for the Detection and Quantification of Early Atherosclerosis: A FAMILIA Substudy
Authors: Rodrigo Fernandez-Jimenez, Christine Graziano-Zill, Latifa Benkader, Raquel Diaz-Munoz, Risa Jaslow, Andrew Kasarskis, Roger J Hajjar, Daniella Kadian-Dodov, Zahi A Fayad, Valentin Fuster
Journal: Circulation (2018)

Introduction: Three-dimensional vascular ultrasound (3DVUS) offers promise for cardiovascular risk stratification in the general population. However, 3DVUS reproducibility in early stages of athero...
Occupational health outcomes among international migrant workers: a systematic review and meta-analysis
Authors: Sally Hargreaves, Kieran Rustage, Laura B Nellums, Alys McAlpine, Nicola Pocock, Delan Devakumar, Robert W Aldridge, Ibrahim Abubakar, Kristina L Kristensen, Jan W Himmels, Jon S Friedland, Cathy Zimmerman
Journal: The Lancet Global Health (2019)

Globally, there are more than 150 million international migrant workers-individuals who are employed outside of their country of origin-comprising the largest international migrant group. A substantial number of migrants work in hazardous and exploitative environments, where they might be at considerable risk of injury and ill health. However, little data on occupational health outcomes of migrant workers exist, with which to inform global policy making and delivery of health services.
ELECTROHYDRAULIC LITHOTRIPSY IN CASE OF SEVERE BILE DUCT STONES AFTER BILROTH-II
Authors: A Filin
Journal: Endoscopy (2019)

Patient, male, 76 years old, addmitted to our hospital with diagnosis: bile stone disease, obstructive jaundice with bilirubin 21 mg/dl, bile duct stones with biliary hypertension. Bilroth-II stomach resection due to ulcer bleeding 30 years ago. Common bile duct – 20 mm, common hepatic duct – 15 mm, cystic duct – 8 mm. Multiple bile duct stones of barrel and cubic shape, 25*20 mm in size. According to our experience, side-viewing duodenoscope is not a best choice in Bilroth-II cases. We performed duodenoscopy with forward-viewing HD-scope, canulated papilla, initiated cholangiography. We performed sphincerotomy with a sphincterotome, developed for reverse EST in Bilroth-II cases. Barrel-shaped triangular and cubic stones are the most challenging for endoscopic extraction. So, we failed to treat patient in routine way. Further methods of treatment offered: extracorporal distant shockwave lithotripsy, percutaneous transhepatic drainage, surgery and endoscopic choledohoscopy with direct lithotripsy. Endoscopt seemed to be the most balanced between risks and benefits of treatment. We repeated duodenoscopy with standart forward-looking 9 mm diameter HD-scope with instrumental channel 2.8 mm. As EST was already performed we could easily enter the bile duct with the scope. Cholangioscopy was performed wth water filling and without gas inflation. We visualised bile duct stones and crushed them with direct contact electrohydraulic lithotripsy with WALZ system. The procedure took onr hour and 20 minutes. The procedure was performed with propofol sedation in our ERCP room.