tbuckley/cabot-search huggingface dataset:
Dose and Timing of N‐Cadherin Mimetic Peptides Regulate MSC Chondrogenesis within Hydrogels
Authors: Mi Y. Kwon, Sebastián L. Vega, William M. Gramlich, Minwook Kim, Robert L. Mauck, Jason A. Burdick
Journal: Advanced Healthcare Materials (2018)

Abstract The transmembrane glycoprotein N‐cadherin (NCad) mediates cell–cell interactions found during mesenchymal condensation and chondrogenesis. Here, NCad‐derived peptides (i.e., HAV) are incorporated into hyaluronic acid (HA) hydrogels with encapsulated mesenchymal stem cells (MSCs). Since the dose and timing of NCad signaling are dynamic, HAV peptide presentation is tuned via alterations in peptide concentration and incorporation of an ADAM10‐cleavable domain between the hydrogel and the HAV motif, respectively. HA hydrogels functionalized with HAV result in dose‐dependent increases in early chondrogenesis of encapsulated MSCs and resultant cartilage matrix production. For example, type II collagen and glycosaminoglycan production increase ≈9‐ and 2‐fold with the highest dose of HAV (i.e., 2 × 10 −3 m ), respectively, when compared to unmodified hydrogels, while incorporation of an efficient ADAM10‐cleavable domain between the HAV peptide and hydrogel abolishes increases in chondrogenesis and matrix production. Treatment with a small‐molecule ADAM10 inhibitor restores the functional effect of the HAV peptide, indicating that timing and duration of HAV peptide presentation is crucial for robust chondrogenesis. This study demonstrates a nuanced approach to the biofunctionalization of hydrogels to better emulate the complex cell microenvironment during embryogenesis toward stem‐cell‐based cartilage production.
Commensal regulation of T cell survival through Erdr1
Authors: Allison M. Weis, Raymond Soto, June L. Round
Journal: Gut Microbes (2018)

The commensal microbiota influences many aspects of immune system regulation, including T cells, but molecular details of how this occurs are largely unknown. Here we review our findings that the microbiota regulates Erdr1, a secreted apoptotic factor, to control T cell survival. Erdr1 is highly upregulated in CD4+ T cells from germfree mice and antibiotic treated animals, and our study shows that Erdr1 is suppressed by the microbiota via Toll-like receptor signaling and MyD88 dependent pathways. Erdr1 functions in an autocrine fashion and promotes apoptosis through the FAS/FASL pathway. Suppression of Erdr1 leads to survival of autoreactive T cells and exacerbated autoimmune disease in the EAE model, and overexpression of Erdr1 results in lessened disease. This novel T cell apoptotic factor has implications for autoimmunity, cancer biology, and invasive pathogens and thus represents a novel therapeutic target in disease.
I Solemnly Share
Authors: Rahael Gupta
Journal: JAMA (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 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
Lost in Translation: Linking Biomedical Research and Clinical Practice at the National Institutes of Health, 1977 to 2013
Authors: Todd M. Olszewski
Journal: Annals of Internal Medicine (2018)

This article examines the history and effect of the Consensus Development Program (CDP) at the National Institutes of Health (NIH). Introduced at a time when the relationship between the U.S. public and the medical profession was at a nadir, the CDP frequently placed the NIH in the middle of broader debates in medical practice and health policy during the last quarter of the 20th century. Drawing on published and archival sources, this paper sheds light on the challenges associated with collecting, assessing, and communicating evidence to medical professionals and convincing them to act on it in the name of improved health care. Administrators at the NIH sought a middle ground between changing medical practice and respecting professional autonomy, with varying degrees of success. This debate has continued implications today as tensions persist between scientific guidelines and the clinical medicine practiced by physicians and expected by patients.
The prognostic significance of tumor-infiltrating lymphocytes for primary melanoma varies by sex
Authors: Andrew J. Sinnamon, Cimarron E. Sharon, Yun Song, Madalyn G. Neuwirth, David E. Elder, Xiaowei Xu, Emily Y. Chu, Michael E. Ming, Douglas L. Fraker, Phyllis A. Gimotty, Giorgos C. Karakousis
Journal: Journal of the American Academy of Dermatology (2018)
Recognizing the Top Reviewers of 2017 for <i>Circulation Research</i>
Authors: Roberto Bolli
Journal: Circulation Research (2018)

A journal can only be as good as its reviewers.The Editors of Circulation Research wish to acknowledge the following reviewers, who have distinguished themselves for exemplary performance and outstanding contributions to the journal.They have selflessly donated their time (often on weekends and evenings), their energy, and their expertise to assist the editors in the difficult task of selecting
The Changing Face of Noncardia Gastric Cancer Incidence Among US Non-Hispanic Whites
Authors: William F Anderson, Charles S Rabkin, Natalie Turner, Joseph F Fraumeni, Philip S Rosenberg, M Constanza Camargo
Journal: JNCI Journal of the National Cancer Institute (2017)

The initial step for noncardia gastric carcinogenesis is atrophic gastritis, driven by either Helicobacter pylori infection or autoimmunity. In recent decades, the prevalence rates of these two major causes declined and increased, respectively, with changes in Western lifestyles. We therefore assessed gastric cancer incidence trends for US race/ethnic groups, 1995-2013.Age-standardized rates (ASRs) from 45 North American Association of Central Cancer Tumor Registries were summarized by estimated annual percentage change (EAPC) and 95% confidence intervals (CIs). Age period cohort models supplemented standard descriptive techniques and projected future trends.There were 137 447 noncardia cancers in 4.4 billion person-years of observation. Among non-Hispanic whites, the ASR was 2.2 per 100 000 person-years, with an EAPC of -2.3% (95% CI = -2.0% to -2.6%). Notwithstanding this overall decline, EAPCs rose 1.3% (95% CI = 0.6% to 2.1%) for persons younger than age 50 years and fell -2.6% (95% CI = -2.4% to -2.9%) for older individuals. These converging trends manifested a birth cohort effect more pronounced among women than men, with incidence among women born in 1983 twofold (95% CI = 1.1-fold to 3.6-fold) greater than those born in 1951. Age interaction was also statistically significant among Hispanic whites, with slightly increasing vs decreasing EAPCs for younger and older individuals, respectively. Incidence declined regardless of age for other races. Current trends foreshadow expected reversals in both falling incidence and male predominance among non-Hispanic whites.Dysbiosis of the gastric microbiome associated with modern living conditions may be increasing risk of autoimmune gastritis and consequent noncardia cancer. The changing face by age and sex of gastric cancer warrants analytical studies to identify potential causal mechanisms.
Niclosamide in combination with abiraterone and prednisone in men with castration-resistant prostate cancer (CRPC): initial results from a phase Ib/II trial.
Authors: Chong-xian Pan, Primo Lara, Christopher P. Evans, Mamta Parikh, Marc Dall'era, Chengfei Liu, Daniel Robles, Allen Gao
Journal: Journal of Clinical Oncology (2018)

192 Background: Prostate cancer is driven by androgen receptor (AR) signaling. The variant AR-V7 lacks the ligand binding domain, constitutively activates the AR pathway, and confers resistance to Abiraterone (Abi) and enzalutamide (Enza). We discovered that the anti-helminthic drug niclosamide targets AR-V7 and sensitizes resistant CRPC to Enza and Abi. We hypothesize that niclosamide/PDMX1001 potentiates the efficacy of Abi against CRPC. Here we report the initial results of this ongoing investigator-initiated phase Ib/II trial. Methods: Eligible patients (pts) have progressive CRPC with serum testosterone &lt; 50 ng/dl. No prior Abi was allowed. In the Phase Ib cohort, pts received Abi 1000 mg PO qd, prednisone 5 mg PO bid, with intrapatient dose-escalation of niclosamide/PDMX1001 from 400 mg PO bid to 1600 mg PO tid. Trough niclosamide/PDMX1001 levels were measured. The Phase II cohort will enroll 27 patients with detectable AR-V7 in the peripheral blood. Co-primary endpoints include toxicity and response as determined by the Prostate Cancer Working Group 2 criteria. Results: Of 6 pts (age 74-83) in the Phase Ib cohort, five pts tolerated a niclosamide/PDMX1001 dose of 1,600 mg po tid without dose limiting toxicity; per protocol, this is the recommended Phase II dose. Niclosamide/PDMX1001 trough level was 0.305 and 0.496 µM in the two pts analyzed thus far, higher than the target level of 0.1µM required for anti-cancer activity. Of 6 pts, two pts achieved complete PSA response ( &lt; 0.01 ng/ml), compared to historical control 0/30 pts treated with Abi alone; two with partial PSA response (≥50% decrease). Of the remaining two pts, one was prematurely taken off from the study after one cycle because of rising PSA, and the other had PSA decrease of 17.1%, but biopsy of the only enlarged lymph node showed all necrotic tissue. The only toxicity was Grade 1 nausea and diarrhea. The Phase II cohort will now enroll. Molecular correlative studies will be presented. Conclusions: The combination of niclosamide/PDMX1001, Abi and prednisone is well tolerated with promising safety and efficacy data. Targeted serum trough levels of niclosamide are clinically achievable. Clinical trial information: NCT02807805.
ROLE OF GALECTIN 3, NGAL AND CYSTATIN C IN RISK ASSESSMENT IN THE SETTING OF ACUTE CORONARY SYNDROME
Authors: Slayman Nabih Obeid, Arnold von Eckardstein, Ruben Loretz, Andrea Denegri, Fiona Koestler, Roland Klingenberg, Baris Gencer, Francois Mach, Lorenz Raber Räber, Stephan Windecker, David Nanchen, Frank Ruschitzka, Felix Tanner, Christian Matter, Thomas F. Luscher
Journal: Journal of the American College of Cardiology (2018)
ABNORMAL MYOCARDIAL BLOOD FLOW WITH NORMAL QUALITATIVE PERFUSION WITH POSITRON EMISSION TOMOGRAPHY MYOCARDIAL PERFUSION IMAGING IN HEART TRANSPLANT RECIPIENTS
Authors: Andrew Noll, Ghina Alaaeddine, Serge Harb, Emer Joyce, Miriam Jacob, Rory Hachamovitch, Paul Cremer, Wael Jaber
Journal: Journal of the American College of Cardiology (2018)
Diploma of the Royal College of Ophthalmologists, London (DRCOphth)
Authors: Lik Thai Lim
Journal: BMJ (2008)

The DRCOphth examination is open to any medically qualified persons with a medical degree which is approved by the General Medical Council. They must have done one year in a preregistration house officer post (or equivalent) acceptable by the GMC and have some ophthalmology experience at postgraduate level (no minimum time specified). It is intended mainly for medical doctors with an interest in ophthalmology who do not wish to practise as a consultant ophthalmologist in the United Kingdom.

I did it in July 2007. This sitting was …
Paediatric CCTs exceed consultant vacancies by 150 a year, college warns
Authors: Abi Rimmer
Journal: BMJ (2013)

The Royal College of Paediatrics and Child Health has raised concern that numbers of newly qualified paediatricians exceeds the number of consultant posts available.

The college has estimated that, between 2014 and 2019, there could be an average surplus of 150 holders of certificates of completion of training (CCTs) in paediatrics.1 The findings come after a survey by the Royal College of Physicians found that, across the profession as a whole, the number of newly qualified …
P063 Effect of adipokines and IL-17 on synovial fibroblast from different rheumatic disease backgrounds
Authors: KW Frommer, S Rehart, M Sauerbier, U Müller-Ladner, E Neumann
Journal: Annals of the Rheumatic Diseases (2018)

<h3>Introduction</h3> Rheumatoid arthritis (RA) and psoriatic arthritis (PsA) have several features in common but also possess distinct differences. Synovial fibroblasts (SF) are known key effector cells in the pathophysiology of RA. We hypothesised that differential responses of SF from patients with PsA and RA to various stimuli including adipokines and cytokines may contribute to those differences. For example, IL-17 (also found in synovial tissue) is of particular therapeutic significance in PsA but not as effective in RA. Thus far, IL-17 in its isoform IL-17A has been the major therapeutic target in PsA but IL-17F also plays a role in the IL-23/IL-17 axis of inflammatory diseases. <h3>Objectives</h3> Therefore, we analysed the responses of SF from patients with PsA, RA or no rheumatic disease to IL-17A/F±TNF-α and selected adipokines. <h3>Methods</h3> SF were isolated from patients with PsA, RA or non-rheumatic disease controls (N), each undergoing joint surgery. PsASF, RASF and NSF were stimulated with recombinant IL-17A/F, TNF-, visfatin, and resistin. A neutralising anti-IL-17A antibody was used to verify specificity of the IL-17A effects. Secretion of the proinflammatory cytokine IL-6 was used as the initial readout parameter and was quantified using a commerical immunoassay. <h3>Results</h3> Stimulation with visfatin caused a strong increase in IL-6 secretion in all SF types (n=3 each), while resistin had no effect. Differences in responses were not statistically significant between the SF types studied. IL-17A at concentrations found in serum or synovial fluid did not induce IL-6 secretion in any of the SF. Dose-response curve analysis showed that considerably higher concentrations of IL–17A, which may occur locally in tissue, are required for the induction of IL-6 secretion. An anti-IL–17A antibody abolished the effect, thus showing that the effect is specific for IL-17A. The effects of IL-17A and IL–17F on IL-6 secretion by PsASF could be strongly amplified by a co–stimulation with TNF-α (IL-17A: 5-fold vs 113-fold; IL-17F: 1.7-fold vs 39-fold; TNF-α alone: 12-fold). The effects were stronger for IL-17A than for IL–17F with or without TNF co–stimulation. No effect of IL–17F alone was observed on NSF (n=1). <h3>Conclusions</h3> SF from RA and PsA were not differentially affected by the adipokines visfatin and resistin or IL-17A when used at serum or synovial fluid concentrations. The property of IL-17F not affecting NSF but PsASF (and RASF) may be beneficial in its use as therapeutic target. <h3>Acknowledgements</h3> This work was supported by an unrestricted educational grant from Celgene GmbH. <h3>Disclosure of interest</h3> None declared
STATIN USE IN US ADULTS WITH CHRONIC KIDNEY DISEASE: A COMPARISON OF TREATMENT GUIDELINES
Authors: Matthew Mefford, Robert Rosenson, Vera Bittner, Rikki Tanner, Luqin Deng, Monika M. Safford, Blai Coll, Katherine Mues, Keri Monda, Paul Muntner
Journal: Journal of the American College of Cardiology (2018)
Abstract P4-09-10: Nomogram for predicting lymph node involvement in patients with invasive micropapillary carcinoma of breast: A SEER population-based study
Authors: F Ye, X Hu, Z Shao
Journal: Cancer Research (2018)

Abstract Background: Invasive micropapillary carcinoma (IMPC) is an unusual and distinct subtype of invasive breast tumor with high propensity for regional lymph node metastases. Because of its lymphotropic nature at initial presentation, IMPC is considered to have an unfavorable prognosis when compared with invasive ductal carcinoma (IDC). The aim of this study was to identify risk factors accounting for its lymphotropic features and to develop a nomogram to predict the probability of lymph node involvement in IMPC. Patients and Methods: A retrospective review of the clinical and pathology records was performed in patients diagnosed with IMPC between 2003 and 2014 from Surveillance, Epidemiology, and End Results (SEER) database. Training set comprised patients diagnosed between 2003 and 2009, while validation set included patients diagnosed thereafter. Ethical approval of the study was granted by the Institutional Review Board of Fudan University Shanghai Cancer Center. Multiple logistic regression analysis was conducted. A logistic regression model was used to construct the nomogram in the training set and then validated in the validation set. Nomogram performance was quantified with respect to discrimination and calibration. Results: Overall, 1407 patients diagnosed with IMPC were enrolled, of which 527 in training set and 880 in validation set. The demographic characteristics were comparable within sets. Larger lesion, younger age at diagnosis, black ethnic and lack of hormone receptor expression were significantly related to regional nodes involvement. The AUC of the nomogram was 0.735 (95 percent confidence interval 0.692 to 0.777), demonstrating a good prediction performance. A calibration curve for the nomogram was plotted to evaluate the agreement between actual (observed) outcomes and expected probabilities. The slope of the calibration curve was close to 1, which indicated excellent calibration of the nomogram. The performance of the nomogram was further validated in the validation set, in which AUC was 0.734 (95 percent confidence interval 0.701 to 0.767). Conclusions: The striking difference between IMPC and IDC remains the increased lymph node involvement in IMPC and therefore merits aggressive treatment. The nomogram based on the clinical parameters was established, which could accurately predict regional lymph node status. This nomogram would facilitate evaluating lymph node state preoperatively and thus treatment decision-making of individual patients, especially in neoadjuvant settings. Citation Format: Ye F, Hu X, Shao Z. Nomogram for predicting lymph node involvement in patients with invasive micropapillary carcinoma of breast: A SEER population-based study [abstract]. In: Proceedings of the 2017 San Antonio Breast Cancer Symposium; 2017 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2018;78(4 Suppl):Abstract nr P4-09-10.
A Life in Food: A Grain of Salt and Some Humble Pie
Authors: Michael J. Gibney
Journal: Annual Review of Nutrition (2018)

From my senior school days, I had wanted to pursue a career in food. In quite what capacity I was not too sure. So my starting points were within the fields of animal nutrition before moving for the major part of my career to medical schools to study human nutrition and health. My career scientific achievements lie within the Kuhnian spectrum of normal science, but within that normality, I was always one to challenge conventional wisdom. An academic career is about more than just research. It is about teaching and not just the minutiae of nutrition, but about life and living, about challenges and failures. Reflecting on the experience of that career, my advice to early stage researchers is this: Be patient, determined, and resilient in the very early stages. Hold no fear of change and be courageous in challenging conventional wisdom. Always favor openness and collaboration and always seek to help others. Citation indices are important to your career, but these other avenues that I advise you to follow are what you will eventually be most proud of.
Handling information overload
Authors: Mark Griffiths
Journal: BMJ (2005)

Information management is an important skill that can be learned. We are all bombarded by information daily and need to know how to handle it.

Know what, where, and who you need to know —Time can be saved by knowing where to look and who can help you. It helps to have a mentor to help know where to find it. Also, only look for what you need …
Female doctors should form personal relationships with senior role models, researchers say
Authors: Abi Rimmer
Journal: BMJ (2014)

Female doctors must be given opportunities to develop close personal relationships with senior colleagues who can act as role models, Exeter University researchers have argued.

A study carried out by Kim Peters and Michelle Ryan from the university, in partnership with the Medical Women’s Federation, examined whether female doctors benefited from having role models. The researchers found that female doctors benefited from role models with whom they had formed close personal relationships. However, other, more standard, interventions designed to support women in their careers, such as increasing the …
Caspase-3, a key apoptotic protein, as a prognostic marker in gastric cancer after curative surgery
Authors: Kuo-Hung Huang, Wen-Liang Fang, Anna Fen-Yau Li, Po-Huang Liang, Chew-Wun Wu, Yi-Ming Shyr, Muh-Hwa Yang
Journal: International Journal of Surgery (2018)