tbuckley/cabot-search huggingface dataset:
VE-Cadherin–Mediated Epigenetic Regulation of Endothelial Gene Expression
Authors: Marco F. Morini, Costanza Giampietro, Monica Corada, Federica Pisati, Elisa Lavarone, Sara I. Cunha, Lei L. Conze, Nicola O’Reilly, Dhira Joshi, Svend Kjaer, Roger George, Emma Nye, Anqi Ma, Jian Jin, Richard Mitter, Michela Lupia, Ugo Cavallaro, Diego Pasini, Dinis P. Calado, Elisabetta Dejana, Andrea Taddei
Journal: Circulation Research (2017)

The mechanistic foundation of vascular maturation is still largely unknown. Several human pathologies are characterized by deregulated angiogenesis and unstable blood vessels. Solid tumors, for instance, get their nourishment from newly formed structurally abnormal vessels which present wide and irregular interendothelial junctions. Expression and clustering of the main endothelial-specific adherens junction protein, VEC (vascular endothelial cadherin), upregulate genes with key roles in endothelial differentiation and stability.
Predictors and outcomes of heart failure with mid‐range ejection fraction
Authors: Vijeta Bhambhani, Jorge R. Kizer, Joao A.C. Lima, Pim van der Harst, Hossein Bahrami, Matthew Nayor, Christopher R. de Filippi, Danielle Enserro, Michael J. Blaha, Mary Cushman, Thomas J. Wang, Ron T. Gansevoort, Caroline S. Fox, Hanna K. Gaggin, Willem J. Kop, Kiang Liu, Ramachandran S. Vasan, Bruce M. Psaty, Douglas S. Lee, Frank P. Brouwers, Hans L. Hillege, Traci M. Bartz, Emelia J. Benjamin, Cheeling Chan, Matthew Allison, Julius M. Gardin, James L. Januzzi, Daniel Levy, David M. Herrington, Wiek H. van Gilst, Alain G. Bertoni, Martin G. Larson, Rudolf A. de Boer, John S. Gottdiener, Sanjiv J. Shah, Jennifer E. Ho
Journal: European Journal of Heart Failure (2017)
Will the FDA’s New Tobacco Strategy Be a Game Changer?
Authors: Rita Rubin
Journal: JAMA (2017)

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 HomeNew OnlineCurrent IssueFor Authors Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More 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 journal
Biomaterials‐Based Approaches to Tumor Spheroid and Organoid Modeling
Authors: Pradip Shahi Thakuri, Chun Liu, Gary D. Luker, Hossein Tavana
Journal: Advanced Healthcare Materials (2017)

Evolving understanding of structural and biological complexity of tumors has stimulated development of physiologically relevant tumor models for cancer research and drug discovery. A major motivation for developing new tumor models is to recreate the 3D environment of tumors and context-mediated functional regulation of cancer cells. Such models overcome many limitations of standard monolayer cancer cell cultures. Under defined culture conditions, cancer cells self-assemble into 3D constructs known as spheroids. Additionally, cancer cells may recapitulate steps in embryonic development to self-organize into 3D cultures known as organoids. Importantly, spheroids and organoids reproduce morphology and biologic properties of tumors, providing valuable new tools for research, drug discovery, and precision medicine in cancer. This Progress Report discusses uses of both natural and synthetic biomaterials to culture cancer cells as spheroids or organoids, specifically highlighting studies that demonstrate how these models recapitulate key properties of native tumors. The report concludes with the perspectives on the utility of these models and areas of need for future developments to more closely mimic pathologic events in tumors.
Public health concerns arising from interventions designed to circumvent polluted surface drinking water in Shenqiu County, Henan, China
Authors: Weidong Qu, Weiwei Zheng, Peter Spencer, Jianheng Zheng, Lan Yang, Fengchan Han, Liyun Yan, Wuren Ma, Ying Zhou, Yuxin Zheng, Youfa Wang
Journal: The Lancet (2017)
Abstract 62: Loss of PERP p53/p63 target gene may indicate tumorigenesis at the margin and local recurrence
Authors: Amanda Simmons, Christina Kong, Rie von Eyben, Laura Attardi, Xiaohui Ma, Quynh-Thu Le, Cherie-Ann Nathan
Journal: Clinical Cancer Research (2017)

Abstract Objectives: PERP (p53 apoptosis effector related to PMP22) localizes to the desmosomal adhesion complexes and is involved in suppressing squamous cell carcinoma (SCC) development. Loss of PERP expression leads to destabilization of desmosome complexes, resulting in enhanced tumor aggressiveness and worse local control in head and neck SCC (HNSCC). We had previously examined PERP loss at surgical margins in a small cohort of HNSCC patients. Results suggested that the loss of PERP may serve as a marker for persistent tumor and predictive of local relapse. Here we validate these findings in an independent patient cohort and report on the combined results of both groups. Materials and Methods: We previously examined the PERP protein expression by immunohistochemistry (IHC) in the surgical mucosal margins of 17 HNSCC patients. The validation cohort consists of 31 patients (15 oral cavity, 11 hypopharynx, 5 larynx). PERP expression was similarly assessed by IHC in the surgical margins of these patients. Finally, we combined the results of both groups to yield 48 patients with HNSCC (18 oral cavity, 12 hypopharynx, 4 oral pharynx, 14 larynx) for competing risk analysis. The relationship between local relapse and PERP expression (positive or negative) was analyzed in a competing risk model with death as a competing risk. Results: In the initial cohort, the 2-year cumulative incidence rate of local relapse was 37.5% for the negative PERP group compared to a 20% for the positive PERP group (p = 0.177). In the validation cohort, the 2-year cumulative incidence rate of local relapse was 50% for the negative PERP group compared to a 15% for the positive PERP group (p = 0.063). Since the results were similar between two groups, we combined them together for additional analyses. In this combined dataset, PERP expression was negative in 18, positive in 26, and not assessable in three patients. Of the 45 analyzable patients, the 2-year cumulative incidence rate of local relapse was 44.4% for the negative PERP group compared to a 16.4% for the positive PERP group (p = 0.010). There was also a trend for worse progression-free survival (p = 0.059) and overall survival (p = 0.085) with the loss of PERP. Conclusions: PERP loss at the surgical margins appears to be associated with a higher risk of local recurrence in HNSCC. These promising results need to be tested in a larger prospective study. Citation Format: Amanda Simmons, Christina Kong, Rie von Eyben, Laura Attardi, Xiaohui Ma, Quynh-Thu Le, Cherie-Ann Nathan. Loss of PERP p53/p63 target gene may indicate tumorigenesis at the margin and local recurrence [abstract]. In: Proceedings of the AACR-AHNS Head and Neck Cancer Conference: Optimizing Survival and Quality of Life through Basic, Clinical, and Translational Research; April 23-25, 2017; San Diego, CA. Philadelphia (PA): AACR; Clin Cancer Res 2017;23(23_Suppl):Abstract nr 62.
Abstract 18273: Novel Anti-Inflammatory Roles of Ikkε in Cardiac Macrophages Contributed to the Cardiac Recovery After Myocardial Infarction
Authors: Ju Hee Kim, Wan Seok Kang, Hye-yun Jeong, Meeyoung Cho, Yong Sook Kim, Youngkeun Ahn
Journal: Circulation (2016)

Introduction:  In the macrophages, NF-κB is a well-known master regulator of inflammation. IKK is an upstream kinase in NF-κB and the role of non-canonical IKKe is unknown in myocardial infarction (MI).   Methods and Results:  RAW264.7 cells were stimulated with LPS with or without ChemA, an NF-κB inhibiting compound. MI was induced in rats and mice, and cardiac function by echocardiography. Mouse bone marrow was isolated and differentiated into macrophages (BMDM) by M-CSF. In stimulated RAW 264.7 cells, proinflammatory mediators such as iNOS, p65 NF-κB, canonical IKKα/β/γ, as well as noncanonical IKKe/TBK1 were notably inhibited by ChemA. Vehicle (Veh) or ChemA were given to MI rats for 2 weeks, and EF was 33.5±4.7 % in the Veh group and 43.5±2.0 % in the ChemA group (p   Conclusions:  The therapeutic effect of ChemA was resulted from stronger inhibition of canonical NF-κB over noncanonical IKKe. Our findings showed IKKe limited chronic inflammation in cardiac macrophages. Here, we suggest that selective inhibition of canonical NF-κB and discriminated activation of IKKe might be an outstanding strategy for cardiac repair.
Surveillance de la résistance aux antibiotiques des pathogènes invasifs : l’expérience de l’Estonie
Authors: K Loivukene, K Kermes, E Sepp, V Adamson, P Mitt, Ü Kallandi, K Otter, P Naaber
Journal: Eurosurveillance (2006)

L’etude presentee ici a pour but d’evaluer les besoins en termes de surveillance des pathogenes invasifs a Gram negatif en Estonie. Les donnees de sensibilite aux antibiotiques des isolats invasifs de Acinetobacter baumannii, Pseudomonas aeruginosa, Klebsiella spp, Escherichia coli, Staphylococcus aureus, Streptococcus pneumoniae et des enterocoques ont ete collectees conformement aux protocoles d’EARSS (European Antimicrobial Resistance Surveillance System). Si le taux de pathogenes a Gram positif est superieur a celui des Gram negatif, en revanche le taux de resistance aux antibiotiques chez les premieres est moindre. Le plus fort taux de resistance etait associe, en particulier, a A. baumannii et P. aeruginosa. La proportion de souches productrices de beta-lactamases a spectre elargi (BLSE) etait de 23% pour Klebsiella spp. et de 3,6% pour E. coli. Inclure les pathogenes invasifs a Gram negatif dans la surveillance de la resistance antimicrobienne permet de disposer d’informations utiles sur la sensibilite des pathogenes locaux, ainsi que pour le traitement empirique d’infections suspectees.
Role of Lymphoid Blasts and Derived Microparticles in Thromboembolic Events during Acute Lymphoblastic Leukaemia: Study of Procoagulant Effect of Vincristine on Jurkat Acute Lymphoid Leukaemia Cell Line
Authors: Claire Pluchart, Gregory Guimard, Maud Colinart, Gael Poitevin, Philippe Nguyen
Journal: Blood (2016)
Should postgraduate training places be reserved for UK graduates? No
Authors: Edwin Borman
Journal: BMJ (2007)

Rumblings of revolution can be heard within the medical profession. What with relentless reforms to the health service, threats to our professionalism, the chaos of the medical training application service (MTAS), and a very real risk of doctors being unemployed, the forces of “blame someone,” “get rid of all of them,” and “I want the best for me and my own” have been let loose.

But that does not justify shutting the door on our colleagues who have come from abroad to work and train beside us in the United Kingdom. Just the opposite; when we prepare to “staff” the barricades, it is worth remembering that “United we stand, divided we fall.”

For most of the lifespan of the NHS, the UK has had an implicit policy to rely on international medical graduates to “top-up” the number of UK graduates. Such a system is cheaper (doctors coming from abroad bring their qualifications to the UK for free), it is more amenable to changing needs (recruitment of trained doctors within a year, rather than having to wait for them to graduate), and it provides for a sharing of experience and the development of healthcare links in a world where disease is globalised and medicine needs to be. The current medical workforce figures confirm this: 36% of doctors registered to practise in the NHS qualified abroad.1
Control of polarization and tumoricidal activity of macrophages by multicellular spheroid formation
Authors: Yutaro Tanaka, Makiya Nishikawa, Yuya Mizukami, Kosuke Kusamori, Yuka Ogino, Shunsuke Nishimura, Kazunori Shimizu, Satoshi Konishi, Yuki Takahashi, Yoshinobu Takakura
Journal: Journal of Controlled Release (2017)
Acute rotator cuff tears
Authors: Richard Craig, Tim Holt, Jonathan Lloyd Rees
Journal: BMJ (2017)

### What you need to know

A 45 year old woman falls on ice and injures her shoulder. Assessment at her local hospital reveals bruising only and no bony injury on plain radiographs. Despite ongoing reassurance and participation in a physiotherapy programme for three months, she continues to complain of pain, weakness, and inability to raise her arm. Eventually she is referred to a specialist shoulder clinic, where an ultrasound scan confirms she has suffered an acute full thickness tear of her supraspinatus tendon. 

Failing to identify an acute full thickness rotator cuff tear is a common problem, and this article is aimed at raising awareness of the condition and its correct management. The article is directed to all clinicians, but especially emergency department clinicians, trauma clinic clinicians, and general practitioners, who tend to see such cases.

The rotator cuff comprises four important muscles (supraspinatus, infraspinatus, teres minor, and subscapularis) which attach close to the humeral head via tendons and are critically involved in stability and function of the shoulder. A rotator cuff tear is when one or more of these tendons tears or detaches from the humerus (fig 1). These tears can vary in size and be acute or chronic. Chronic full and partial thickness tears are due to tendon degeneration and attrition, and these patients …
Abstract IA24: Biomarkers and checkpoint inhibition in HNSCC
Authors: Ezra E. W. Cohen
Journal: Clinical Cancer Research (2017)

Abstract There has been tremendous progress made in development of checkpoint inhibitors in HNSCC with antibodies directed against the PD1/PDL1 axis leading the way. Recent data reveal that these agents are active in patients with refractory disease and improve survival compared with standard of care even in unselected patient populations. Nonetheless, the need for biomarkers to predict which patients benefit most from PD1/PDL1 blockade remains acute while interrogating tissue samples to define mechanisms of resistance is just beginning. To date, it appears that PDL1 expression has some utility to predict activity of PD1/PDL1 blockade. Moreover, gene expression signatures corresponding to an interferon-gamma antitumor response or quantifying mutational burden seem to provide survival predictability. Furthermore, immune signatures of gene expression have been correlated with survival in patients with locally advanced disease. These aspects of checkpoint blockade will be discussed in detail with a view towards where the field is moving in the near term and what to anticipate in the extended future. Citation Format: Ezra E. W. Cohen. Biomarkers and checkpoint inhibition in HNSCC [abstract]. In: Proceedings of the AACR-AHNS Head and Neck Cancer Conference: Optimizing Survival and Quality of Life through Basic, Clinical, and Translational Research; April 23-25, 2017; San Diego, CA. Philadelphia (PA): AACR; Clin Cancer Res 2017;23(23_Suppl):Abstract nr IA24.
Closing In on Treatment for Hemophilia B
Authors: Matthew Porteus
Journal: New England Journal of Medicine (2017)

Hemophilia is an X-linked recessive genetic bleeding disorder that occurs in two major forms. Approximately 80% of patients with hemophilia have mutations in the factor VIII clotting-factor gene (hemophilia A), and approximately 20% have mutations in the factor IX clotting factor gene (hemophilia B). The untreated severe forms of hemophilia (<1% of normal functional clotting activity) are characterized by recurrent spontaneous bleeds into deep tissues and joints that result in severe disabilities and early death. Hemophilia therapy has been characterized by stepwise improvements as new therapies improve on previous ones. One remarkable improvement was the development of recombinant clotting factors . . .
Optimization of Dose Regimen for ALXN1210, a Novel Complement C5 Inhibitor, in Patients with Paroxysmal Nocturnal Hemoglobinuria (PNH): Results of 2 Phase 1/2 Studies
Authors: Alexander Roeth, Scott T. Rottinghaus, Anita Hill, Jin Seok Kim, Hubert Schrezenmeier, Louis Terriou, Alvaro Urbano-Ispizua, Richard A. Wells, Jun Ho Jang, Jeff Szer, Rasha Aguzzi, Eric Scott Bachman, Andrew I. Damokosh, Lori Shafner, Jong-Wook Lee
Journal: Blood (2017)
La estrategia de la Comunidad europea contra la resistencia antimicrobiana
Authors: S Bronzwaer, A Lönnroth, R Haigh
Journal: Eurosurveillance (2004)

En 2001, la Comision europea presentaba una  Estrategia comunitaria contra la resistencia antimicrobiana . Durante los anos anteriores, se instituyeron un numero siempre creciente de medidas aisladas para enfrentar ese problema. La estrategia definida por la Comision permite un enfoque comunitario global en todos los sectores concernidos. Quince acciones en cuatro sectores esenciales incluyen la vigilancia, la prevencion, la busqueda y el incremento de productos, y la cooperacion internacional. Las  recomendaciones del Consejo sobre el uso prudente de antibioticos en medicina humana  tienen un papel importante en esta estrategia. Este documento proporciona un conjunto detallado de las acciones de salud publica para controlar la resistencia antimicrobiana. 
El articulo presenta los once puntos de accion de la estrategia directamente ligada a la medicina humana, asi como las actividades de la Comunidad europea en relacion a este asunto. La resistencia antimicrobiana es una prioridad en el nuevo programa de busqueda de la Union europea.
Dalla sorveglianza epidemiologica all'integrazione europea
Authors: F Tissot
Journal: Eurosurveillance (1999)

Tra i mesi di Marzo e Giugno del 1999, sono arrivati in Albania 442.000 profughi kosovari. Poiche il sistema di sorveglianza nazionale non era preparato a questo evento, e stato istituito un sistema di sorveglianza d'emergenza sulle malattie infettive, per identificare e controllare potenziali focolai epidemici tra i profughi. In questo numero, Eurosurveillance presenta un articolo con i risultati delle prime nove settimane di sorveglianza sulle malattie infettive tra profughi kosovari in Albania, a distanza di cinque mesi dall'inizio dei conflitti nella ex-Jugoslavia. Gli epidemiologi dell'Institut de Veille Sanitaire (InVS), su richiesta del governo francese, hanno partecipato agli aiuti umanitari dal momento che i profughi sono arrivati in Albania. Infatti, esperienze precedenti ci hanno insegnato come sia importante agire tempestivamente, per valutare le condizioni di salute dei profughi, creare collegamenti con la rete di sorveglianza locale o definire e migliorare strategie e strumenti di sorveglianza e di intervento adeguato.
The PNPLA3 SNP rs738409:G allele is associated with increased liver disease-associated mortality but reduced overall mortality in a population-based cohort
Authors: Peter J. Meffert, Katja D. Repp, Henry Völzke, F. Ulrich Weiss, Georg Homuth, Jens P. Kühn, Markus M. Lerch, Ali A. Aghdassi
Journal: Journal of Hepatology (2017)
NKG2D-Based CAR T Cells and Radiotherapy Exert Synergistic Efficacy in Glioblastoma
Authors: Tobias Weiss, Michael Weller, Matthias Guckenberger, Charles L. Sentman, Patrick Roth
Journal: Cancer Research (2017)

Chimeric antigen receptor (CAR) T-cell therapy is an emerging immunotherapy against several malignancies including glioblastoma, the most common and most aggressive malignant primary brain tumor in adults. The challenges in solid tumor immunotherapy comprise heterogenously expressed tumor target antigens and restricted trafficking of CAR T cells to and impaired long-term persistence at the tumor site, as well as the unaddressed integration of CAR T-cell therapy into conventional anticancer treatments. We addressed these questions using a NKG2D-based chimeric antigen receptor construct (chNKG2D) in fully immunocompetent orthotopic glioblastoma mouse models. ChNKG2D T cells demonstrated high IFNγ production and cytolytic activity in vitro Upon systemic administration in vivo, chNKG2D T cells migrated to the tumor site in the brain, did not induce adverse events, prolonged survival, and cured a fraction of glioma-bearing mice. Surviving mice were protected long-term against tumor rechallenge. Mechanistically, this was not solely the result of a classical immune memory response, but rather involved local persistence of chNKG2D T cells. A subtherapeutic dose of local radiotherapy in combination with chNKG2D T-cell treatment resulted in synergistic activity in two independent syngeneic mouse glioma models by promoting migration of CAR T cells to the tumor site and increased effector functions. We thus provide preclinical proof-of-concept of NKG2D CAR T-cell activity in mouse glioma models and demonstrate efficacy, long-term persistence, and synergistic activity in combination with radiotherapy, providing a rationale to translate this immunotherapeutic strategy to human glioma patients.Significance: These findings provide evidence for synergy of conventional anticancer therapy and CAR T cells and heralds future studies for other treatment combinations. Cancer Res; 78(4); 1031-43. ©2017 AACR.
Differential impact of RB status on E2F1 reprogramming in human cancer
Authors: Christopher McNair, Kexin Xu, Amy C. Mandigo, Matteo Benelli, Benjamin Leiby, Daniel Rodrigues, Johan Lindberg, Henrik Gronberg, Mateus Crespo, Bram De Laere, Luc Dirix, Tapio Visakorpi, Fugen Li, Felix Y. Feng, Johann de Bono, Francesca Demichelis, Mark A. Rubin, Myles Brown, Karen E. Knudsen
Journal: Journal of Clinical Investigation (2017)

The tumor suppressor protein retinoblastoma (RB) is mechanistically linked to suppression of transcription factor E2F1-mediated cell cycle regulation. For multiple tumor types, loss of RB function is associated with poor clinical outcome. RB action is abrogated either by direct depletion or through inactivation of RB function; however, the basis for this selectivity is unknown. Here, analysis of tumor samples and cell-free DNA from patients with advanced prostate cancer showed that direct RB loss was the preferred pathway of disruption in human disease. While RB loss was associated with lethal disease, RB-deficient tumors had no proliferative advantage and exhibited downstream effects distinct from cell cycle control. Mechanistically, RB loss led to E2F1 cistrome expansion and different binding specificity, alterations distinct from those observed after functional RB inactivation. Additionally, identification of protumorigenic transcriptional networks specific to RB loss that were validated in clinical samples demonstrated the ability of RB loss to differentially reprogram E2F1 in human cancers. Together, these findings not only identify tumor-suppressive functions of RB that are distinct from cell cycle control, but also demonstrate that the molecular consequence of RB loss is distinct from RB inactivation. Thus, these studies provide insight into how RB loss promotes disease progression, and identify new nodes for therapeutic intervention.