tbuckley/cabot-search huggingface dataset:
Basic thoracic ultrasound skills for chest physicians
Authors: Elspeth Potton
Journal: BMJ (2008)

A recent alert from the National Patient Safety Agency has highlighted to clinicians the risks associated with insertion of chest drains.1 There has been an increase in the number of reported adverse incidents during chest drain insertion. The reasons behind this apparent increase are not clear and are likely to be multifactorial. Many clinicians feel it is safer for pleural procedures to be done under ultrasound or radiological guidance. Traditionally, thoracic ultrasound examinations have been performed by radiologists, but opinion is growing that they could, and perhaps should, be done by the clinicians (usually chest physicians) who perform …
Abstract P1-01-08: DPYSL3 modulates proliferation and migration in claudin-low breast cancer
Authors: R Matsunuma, DW Chan, B-J Kim, P Singh, A Han, A Malovannaya, CM Perou, MJ Ellis
Journal: Cancer Research (2018)

Abstract Cancer is often driven by deregulated protein kinases pathways including breast cancer. To profile the kinome at the protein level we are developing a kinase pulldown (KiP) proteomic platform that uses multiple kinase inhibitors conjugated to sepharose beads for protein kinase profiling. Mass spectrometry-base tryptic peptide sequencing is used to identify and quantify the kinome in an unbiased manner. To date, we have profiled and analyzed the kinomes of more than 50 breast cancer PDX model systems that include all five breast cancer subtypes. In these analyses we have begun to explore the kinome interactome because we have observed that KiP also pulls down breast cancer subtype specific kinase interacting proteins that may represent new biological insights. For example we have consistently identified dihydropyrimidinase-like 3 (DPYSL3) in p21-activated kinase (PAK) inhibitor KiP interactome in the claudin-low WHIM12 PDX model. DPYSL3 is an intracellular phosphoprotein known to play a role in cell migration and metastasis. However it remains to be seen if DPYSL3 functions as a suppressor or a promoter of metastasis. We therefore generated DPYSL3 knock-down cell lines to evaluate function in claudin-low breast cancer. Proliferation levels of DPYSL3 depleted Claudin-low WHIM12 cells (DPYSL3-) were lower than those of control WHIM 12 (DPYSL3+) cells. In contrast, migration levels of DPYSL3- WHIM12 were greater than those of control cells, suggesting a pivotal role for DPYSL3 in several cellular physiologies. Additionally the activity of a PAK inhibitor (FRAX597) on migration appeared to require DPYSL3, as the inhibitory effect of FRAX579 on migration in WHIM12 was lost when DPYSL3 expression was depleted. Additionally we find that only the long isoform of DPYSL3, not a short isoform, interacts with PAK to regulate migration, suggesting that alternative splicing of DPYSL3 may an important to the control of migration. Furthermore Snail is also negatively regulated DPYSL3 with elevated expression in DYPSL3- cells. In conclusion, the study of the kinome interactome in breast cancer PDX identified DPYSL3 as regulator of the PAK family of kinases in a claudin low breast cancer. DPYSL3 is necessary for PAK to promote migration and may play a pivotal role in complex cellular transitions from a proliferative state versus an EMT/cell migratory state. Citation Format: Matsunuma R, Chan DW, Kim B-J, Singh P, Han A, Malovannaya A, Perou CM, Ellis MJ. DPYSL3 modulates proliferation and migration in claudin-low breast cancer [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 P1-01-08.
BMA issues detailed rebuttal of 2013-14 QOF proposals
Authors: Helen Jaques
Journal: BMJ (2013)

Proposed changes to the Quality and Outcomes Framework (QOF) element of the GP contract for England were likely to have “serious implications” for patients and practices, the BMA has said.

The association has submitted an early response to the government’s consultation on the new general medical services (GMS) contract for 2013-14 that outlines its concerns about the proposals for QOF.

Its General Practitioners Committee added that it was “surprised” that detailed guidance on the framework for 2013-14 had …
OSCEs in Psychiatry
Authors: Maire Cooney
Journal: BMJ (2005)

Edited by Ranga Rao

Gaskell Publications, 2005, £20, 208 pages

ISBN 1-904671-17-9

Rating: ⋆⋆⋆⋆⋆/5



Someone once told me the MRCPsych was like a driving test. I think it was meant as reassurance. Both cost me a small fortune. There are similarities though; you won't pass a driving test by reading about it and the same goes for clinical exams. OSCEs in Psychiatry makes that clear—none of that “the only revision book you'll ever need” nonsense. Edited by consultant psychiatrist and MRCPsych course organiser Ranga Roa, it's interactive and calls …
Application of light sheet microscopy for qualitative and quantitative analysis of bronchus-associated lymphoid tissue in mice
Authors: David Twapokera Mzinza, Henrike Fleige, Kristin Laarmann, Stefanie Willenzon, Jasmin Ristenpart, Julia Spanier, Gerd Sutter, Ulrich Kalinke, Peter Valentin-Weigand, Reinhold Förster
Journal: Cellular and Molecular Immunology (2018)

Bronchus-associated lymphoid tissue (BALT) develops at unpredictable locations around lung bronchi following pulmonary inflammation. The formation and composition of BALT have primarily been investigated by immunohistology that, due to the size of the invested organ, is usually restricted to a limited number of histological sections. To assess the entire BALT of the lung, other approaches are urgently needed. Here, we introduce a novel light sheet microscopy-based approach for assessing lymphoid tissue in the lung. Using antibody staining of whole lung lobes and optical clearing by organic solvents, we present a method that allows in-depth visualization of the entire bronchial tree, the lymphatic vasculature and the immune cell composition of the induced BALT. Furthermore, three-dimensional analysis of the entire lung allows the qualitative and quantitative enumeration of the induced BALT. Using this approach, we show that a single intranasal application of the replication-deficient poxvirus MVA induces BALT that constitutes up to 8% of the entire lung volume in mice deficient in CCR7, in contrast to wild type mice (WT). Furthermore, BALT induced by heat-inactivated E. coli is dominated by a pronounced T cell infiltration in Cxcr5-deficient mice, in contrast to WT mice.
Perspectives of health care professionals on active surveillance for the management of prostate cancer.
Authors: Fred Saad, Kittie Pang, Margaret Fitch, Veronique Ouellet, Simone Chevalier, Darrel Drachenberg, Antonio Finelli, Jean-Baptiste Lattouf, Alan So, Simon Sutcliffe, Simon Tanguay, Anne-Marie Mes-Masson
Journal: Journal of Clinical Oncology (2018)

81 Background: Active surveillance has gained widespread acceptance as a safe approach for patients with low risk prostate cancer. Despite presenting several advantages for both patients and the health care system, active surveillance is not adopted by all eligible patients. In this study, we evaluated the factors that influence physicians to recommend active surveillance and the barriers that impact adherence to this approach. Methods: We conducted five focus groups with a total of 48 health care providers (HCP) including family physicians, urologists, surgeons, radiation oncologists, fellows, and residents/medical students. These participants were all providing care for men with low risk prostate cancer and had engaged in conversations with men and their families about active surveillance. The experience of these HCP from academic hospitals in four Canadian provinces was captured. A content and theme analysis was performed on the verbatim transcripts to understand HCP decisions in proposing active surveillance and reveal the facilitators that affect the adherence to this approach. Results: Participants agreed that active surveillance is a suitable approach for low risk prostate cancer patients, but expressed concerns on the rapidly evolving and non-standardized guidelines for patient follow-up. They raised the need for additional tools to appropriately identify the patients best suited for active surveillance. Collaborations between urologists, radiation-oncologists, and medical oncologists were favoured, however, the role of general practitioners remained controversial once patients were referred to a specialist. Conclusions: Integration of more reliable tools and/or markers, and more specific guidelines for patient follow-up would help both patients and physicians in the decision-making for active surveillance.
Prevalence of Housing Problems Among Community Health Center Patients
Authors: Travis P. Baggett, Seth A. Berkowitz, Vicki Fung, Jessie M. Gaeta
Journal: JAMA (2018)

Prevalence of Housing Problems Among Community Health Center PatientsIn 2016, the Health Resources and Services Administration (HRSA) Health Center Program provided primary care to more than 25 million medically underserved patients through a nationwide network of community health center (CHC), health care for the homeless, migrant health center, and public housing primary care clinics. 1 Although the latter 3 clinic types serve individuals with housing problems by definition, little is known about the scope of housing problems among CHC patients, who constitute 91% of Health Center Program patients nationally. 1 We used data from a national survey to assess the prevalence and health-related correlates of housing problems among CHC patients.
Politics and Professionalism
Authors: William P. Sexauer
Journal: Annals of Internal Medicine (2018)

On Being a Doctor20 February 2018Politics and ProfessionalismWilliam P. Sexauer, MDWilliam P. Sexauer, MDSidney Kimmel Medical College at Thomas Jefferson University, Philadelphia, Pennsylvania (W.P.S.)Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/M16-2926 Audio Reading - “Politics and Professionalism” Audio. Virginia L. Hood, MD, Annals Associate Editor, reads "Politics and Professionalism," by W.P. Sexauer. Your browser does not support the audio element. Audio player progress bar Step backward in current audio track Play current audio trackPause current audio track Step forward in current audio track Mute current audio trackUnmute current audio track 00:00/ SectionsAboutFull TextPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail After a busy morning of rounding and note writing in the ICU, I decided to use some downtime to catch up on my institutional online training sessions. The title of the latest module struck me as curious: Professionalism. I had always thought of medical professionalism as a set of qualities whose nidus was screened for at medical school and training program admissions and cultivated throughout that education and training. Could professionalism be instilled or enforced through a 10-minute online session akin to those modules teaching us how to respond to a fire in the building? I proceeded to view the ... Author, Article, and Disclosure InformationAffiliations: Sidney Kimmel Medical College at Thomas Jefferson University, Philadelphia, Pennsylvania (W.P.S.)Corresponding Author: William P. Sexauer, MD, Division of Pulmonary and Critical Care Medicine, 834 Walnut Street, Philadelphia, PA 19107; e-mail, william.[email protected]edu. PreviousarticleNextarticle Advertisement Audio Reading - “Politics and Professionalism” Audio. Virginia L. Hood, MD, Annals Associate Editor, reads "Politics and Professionalism," by W.P. Sexauer. Your browser does not support the audio element. Audio player progress bar Step backward in current audio track Play current audio trackPause current audio track Step forward in current audio track Mute current audio trackUnmute current audio track 00:00/ FiguresReferencesRelatedDetailsSee AlsoPolitics and Professionalism William Berger Politics and Professionalism William P. Sexauer Metrics Cited byCivility: A concept analysis revisitedPolitics and ProfessionalismWilliam Berger, MD 20 February 2018Volume 168, Issue 4Page: 299-300KeywordsBehaviorCritical careForecastingHealth careHearingIntensive care unitsMedical educationRacial and ethnic issues ePublished: 20 February 2018 Issue Published: 20 February 2018 Copyright & PermissionsCopyright © 2018 by American College of Physicians. All Rights Reserved.PDF downloadLoading ...
Behavioral Counseling to Prevent Skin Cancer
Authors: David C. Grossman, Susan J. Curry, Douglas K. Owens, Michael J. Barry, Aaron B. Caughey, Karina W. Davidson, Chyke A. Doubeni, John W. Epling, Alex R. Kemper, Alex H. Krist, Martha Kubik, Seth Landefeld, Carol M. Mangione, Michael Silverstein, Melissa A. Simon, Chien-Wen Tseng
Journal: JAMA (2018)

<h3>Importance</h3> Skin cancer is the most common type of cancer in the United States. Although invasive melanoma accounts for only 2% of all skin cancer cases, it is responsible for 80% of skin cancer deaths. Basal and squamous cell carcinoma, the 2 predominant types of nonmelanoma skin cancer, represent the vast majority of skin cancer cases. <h3>Objective</h3> To update the 2012 US Preventive Services Task Force (USPSTF) recommendation on behavioral counseling for the primary prevention of skin cancer and the 2009 recommendation on screening for skin cancer with skin self-examination. <h3>Evidence Review</h3> The USPSTF reviewed the evidence on whether counseling patients about sun protection reduces intermediate outcomes (eg, sunburn or precursor skin lesions) or skin cancer; the link between counseling and behavior change, the link between behavior change and skin cancer incidence, and the harms of counseling or changes in sun protection behavior; and the link between counseling patients to perform skin self-examination and skin cancer outcomes, as well as the harms of skin self-examination. <h3>Findings</h3> The USPSTF determined that behavioral counseling interventions are of moderate benefit in increasing sun protection behaviors in children, adolescents, and young adults with fair skin types. The USPSTF found adequate evidence that behavioral counseling interventions result in a small increase in sun protection behaviors in adults older than 24 years with fair skin types. The USPSTF found inadequate evidence on the benefits and harms of counseling adults about skin self-examination to prevent skin cancer. <h3>Conclusions and Recommendation</h3> The USPSTF recommends counseling young adults, adolescents, children, and parents of young children about minimizing exposure to UV radiation for persons aged 6 months to 24 years with fair skin types to reduce their risk of skin cancer. (B recommendation) The USPSTF recommends that clinicians selectively offer counseling to adults older than 24 years with fair skin types about minimizing their exposure to UV radiation to reduce risk of skin cancer. Existing evidence indicates that the net benefit of counseling all adults older than 24 years is small. In determining whether this service is appropriate in individual cases, patients and clinicians should consider the presence of risk factors for skin cancer. (C recommendation) The USPSTF concludes that the current evidence is insufficient to assess the balance of benefits and harms of counseling adults about skin self-examination to prevent skin cancer. (I statement)
Low frequency of soya allergy in peanut‐allergic children: Relevance to allergen labelling on medicines
Authors: N. Patel, M. Vazquez‐Ortiz, S. Lindsley, D. E. Campbell, P. J. Turner
Journal: Allergy (2018)

Please note: The publisher is not responsible for the content or functionality of any supporting information supplied by the authors. Any queries (other than missing content) should be directed to the corresponding author for the article.
Abstract P4-04-07: Characterization of the effects of estrogen receptor alpha Y537S and D538G mutations on receptor function and pharmacology
Authors: RA Blake, SJ Hartman, TL Kleinheinz, J White, S Daly, R Goodwin, W Zhou, J Liang, X Wang, M O'Rourke, C Metcalfe, L Friedman
Journal: Cancer Research (2018)

Abstract The frontline therapy for estrogen receptor alpha (ERα) positive Breast Cancer (ER+BC) involves various forms of endocrine therapy, consisting of either Selective Estrogen Receptor Modulators (SERMs) or aromatase inhibitors. An emerging mechanism of ER+BC resistance to endocrine therapy, and consequently disease relapse, has been associated with a set of “hotspot” mutations in and near to helix-12 of the ERα ligand binding domain. Selective Estrogen Receptor Degraders/Down-regulators (SERDs), such as GDC-0810, AZD9496 and GDC-0927, represent a current major pharmacological strategy being applied to develop treatments for such resistant ER+BC. Here, we compare 2 of the most frequent ERα hotspot mutations (Y537S and D538G), with ERα wildtype (WT) and the ability of a set of ERα ligands (including GDC-0810, AZD9496 and GDC-0927) to bind, antagonize and degrade ERα. The concentration of each drug required to bind, antagonize or degrade ERα Y537S or ERα D538G was typically higher than that required for ERα WT. Importantly, ERα Y537S is resistant to estradiol stimulated protein degradation and 4-hydroxy-tamoxifen (a major active metabolite of tamoxifen) stabilizes ERα Y537S protein. This represents a potential mechanism of resistance of ERα Y537S ER+BC to Tamoxifen therapy. Citation Format: Blake RA, Hartman SJ, Kleinheinz TL, White J, Daly S, Goodwin R, Zhou W, Liang J, Wang X, O'Rourke M, Metcalfe C, Friedman L. Characterization of the effects of estrogen receptor alpha Y537S and D538G mutations on receptor function and pharmacology [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 P4-04-07.
Abstract PD4-02: Advantageous polypharmacology of abemaciclib revealed by omics profiling of CDK4/6 inhibitors
Authors: M Hafner, CE Mills, K Subramanian, C Chen, SA Boswell, RA Everley, D Juric, PK Sorger
Journal: Cancer Research (2018)

Abstract Small molecule inhibitors of cyclin-dependent kinases (CDK) 4/6 have created new opportunities for the treatment of advanced hormone-receptor positive (HR+) breast cancer and show promise in other malignancies. Three CDK4/6 inhibitors, palbociclib (PD0332991; Ibrance), ribociclib (LEE011; Kisqali), and abemaciclib (LY2835219), which have been approved or are in late stage trials, are reported to be broadly similar although recent data suggest that abemaciclib has distinct single-agent activity in patients and a unique adverse effects profile. Differences in pharmacokinetics and relative potency for CDK4 versus CDK6 are postulated to account for these differences. In this paper, we use molecular and functional profiling by mRNA sequencing, mass spectrometry-based proteomics, and GR-based dose-response assays to obtain complementary views of the mechanisms of action of CDK4/6 inhibitors. We show that abemaciclib, but not ribociclib or palbociclib, is a potent inhibitor of kinases other than CDK4/6, including CDK1/Cyclin B, which appears to cause arrest in the G2 phase of the cell cycle, and CDK2/Cyclin E/A, which is implicated in resistance to palbociclib. Whereas ribociclib and palbociclib induce cytostasis, and cells adapt to these drugs within 2-3 days of exposure, abemaciclib induces cell death and durably blocks cell proliferation. Abemaciclib is active even in retinoblastoma protein (pRb)-deficient cells in which CDK4/6 inhibition by palbociclib or ribociclib is completely ineffective. The degree of polypharmacology of small molecule drugs is increasingly viewed as an important consideration in their design, with implications for efficacy, toxicity, and acquired resistance. In the case of CDK4/6 inhibitors, we propose that abemaciclib polypharmacology elicits unique molecular responses that are likely to be therapeutically advantageous. More generally, we propose that multi-omic approaches are required to fully elucidate the spectrum of targets relevant to drug action in tumor cells. We expect such understanding to assist in stratifying patient populations and ordering sequential therapies when resistance arises. Citation Format: Hafner M, Mills CE, Subramanian K, Chen C, Boswell SA, Everley RA, Juric D, Sorger PK. Advantageous polypharmacology of abemaciclib revealed by omics profiling of CDK4/6 inhibitors [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 PD4-02.
Trends in Racial/Ethnic and Nativity Disparities in Cardiovascular Health Among Adults Without Prevalent Cardiovascular Disease in the United States, 1988 to 2014
Authors: Arleen F. Brown, Li-Jung Liang, Stefanie D. Vassar, Jose J. Escarce, Sharon Stein Merkin, Eric Cheng, Adam Richards, Teresa Seeman, W.T. Longstreth
Journal: Annals of Internal Medicine (2018)

Background: Trends in cardiovascular disparities are poorly understood, even as diversity increases in the United States. Objective: To examine U.S. trends in racial/ethnic and nativity disparities in cardiovascular health. Design: Repeated cross-sectional study. Setting: NHANES (National Health and Nutrition Examination Survey), 1988 to 2014. Participants: Adults aged 25 years or older who did not report cardiovascular disease. Measurements: Racial/ethnic, nativity, and period differences in Life's Simple 7 (LS7) health factors and behaviors (blood pressure, cholesterol, hemoglobin A1c, body mass index, physical activity, diet, and smoking) and optimal composite scores for cardiovascular health (LS7 score ≥10). Results: Rates of optimal cardiovascular health remain below 40% among whites, 25% among Mexican Americans, and 15% among African Americans. Disparities in optimal cardiovascular health between whites and African Americans persisted but decreased over time. In 1988 to 1994, the percentage of African Americans with optimal LS7 scores was 22.8 percentage points (95% CI, 19.3 to 26.4 percentage points) lower than that of whites in persons aged 25 to 44 years and 8.0 percentage points (CI, 6.4 to 9.7 percentage points) lower in those aged 65 years or older. By 2011 to 2014, differences decreased to 10.6 percentage points (CI, 7.4 to 13.9 percentage points) and 3.8 percentage points (CI, 2.5 to 5.0 percentage points), respectively. Disparities in optimal LS7 scores between whites and Mexican Americans were smaller but also decreased. These decreases were due to reductions in optimal cardiovascular health among whites over all age groups and periods: Between 1988 to 1994 and 2011 to 2014, the percentage of whites with optimal cardiovascular health decreased 15.3 percentage points (CI, 11.1 to 19.4 percentage points) for those aged 25 to 44 years and 4.6 percentage points (CI, 2.7 to 6.5 percentage points) for those aged 65 years or older. Limitation: Only whites, African Americans, and Mexican Americans were studied. Conclusion: Cardiovascular health has declined in the United States, racial/ethnic and nativity disparities persist, and decreased disparities seem to be due to worsening cardiovascular health among whites rather than gains among African Americans and Mexican Americans. Multifaceted interventions are needed to address declining population health and persistent health disparities. Primary Funding Source: National Institute of Neurological Disorders and Stroke and National Center for Advancing Translational Sciences of the National Institutes of Health.