tbuckley/cabot-search huggingface dataset:
Caring for our kids or bullying the nation?
Authors: Nyla Khan
Journal: BMJ (2012)

Labour MP Alex Cunningham’s private member’s bill is to be given a second reading in Parliament this year.1 If the bill comes into effect, it will become illegal to smoke in private vehicles carrying children in the UK. The British Medical Association has supported the proposal and suggested extending it to all vehicles.2 In a statement released in October last year, the Royal College of Paediatrics and Child Health stood by the BMA.3

The rationale behind the legislation is not difficult to appreciate; we are aware of …
Abstract BS1-1: High resolution intravital imaging of the mechanism of how breast cancer initiates and sustains systemic dissemination
Authors: J Condeelis
Journal: Cancer Research (2019)

Abstract Multiphoton microscopy of live animals (IVI) has revolutionized our understanding of cancer metastasis. IVI demonstrates that TMEM, the intravasation doorway, composed of a three cell complex: Mena-Hi tumor cell, endothelial cell and Tie2-Hi/VEGF-Hi macrophage, is the only site in breast tumors where tumor cell intravasation occurs1. During tumor progression, macrophage progenitor cells undergo unidirectional transition from migratory to TMEM-associated macrophages2. During and after this macrophage programming, tumor cells migrate with macrophages and chemotax with high persistence to blood vessels under the control of HGF gradients3 arriving at TMEM1. The TMEM structure itself, as well as the signaling pathways unique to tumor cells interacting with TMEM, have been validated as prognostic markers for predicting metastasis in breast cancer patients4-6. These were the first markers of metastasis in clinical use derived from multiphoton intravital imaging. TMEM are found in both primary and metastatic tumor sites of breast cancer7 and in primary and metastatic sites of pancreatic ductal and neuro-endocrine tumors. Clinical trials of TMEM inhibitors, targeting TMEM in both primary and secondary sites8,9, are now underway in breast cancer patients (clinical trials study number NCT02824575). As tumor cells interact with TMEM, MenaINV. expression in the tumor cells occurs in response to macrophage-induced NOTCH signaling10, which drives invadopod assembly/ function, and metastatic seeding11,12. MenaINV expression is necessary for invadopod-mediated transendothelial migration during intravasation at TMEM13 and assures the efficient dissemination of seeding competent and non-dividing tumor cells which, after a delay, contribute to metastatic recurrence at multiple systemic sites. These findings support TMEM as a critical therapeutic target for inhibiting breast cancer metastasis. 1.Harney, A.S. et al. (2015) PMC4560669 2.Arwert, E.N. et al. (2018) PMC5946803 3.Leung, E. et al. (2017) PMC5426963 4.Karagiannis, G.S. et al (2016) PMC4893654 5.Rohan, T.E. et al. (2014) PMC4133559 6.Sparano, J.A. et al. (2017)PMC5678158 7.Entenberg, D. et al. (2018)PMC5755704 8.Harney, A.S. et al. (2017)PMC5669998 9.Karagiannis, G.S. et al. (2017) PMC5592784 10.Pignatelli, J. et al. (2016) PMC5129016 11.Eddy, R.J. et al (2017) PMC5524604 12.Linde, N. et al. (2018) PMC5750231 13.Pignatelli, J. et al.(2014) PMC4266931 Citation Format: Condeelis J. High resolution intravital imaging of the mechanism of how breast cancer initiates and sustains systemic dissemination [abstract]. In: Proceedings of the 2018 San Antonio Breast Cancer Symposium; 2018 Dec 4-8; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2019;79(4 Suppl):Abstract nr BS1-1.
Bacteroides-Derived Sphingolipids Are Critical for Maintaining Intestinal Homeostasis and Symbiosis
Authors: Eric M. Brown, Xiaobo Ke, Daniel Hitchcock, Sarah Jeanfavre, Julian Avila-Pacheco, Toru Nakata, Timothy D. Arthur, Nadine Fornelos, Cortney Heim, Eric A. Franzosa, Nicki Watson, Curtis Huttenhower, Henry J. Haiser, Glen Dillow, Daniel B. Graham, B. Brett Finlay, Aleksandar D. Kostic, Jeffrey A. Porter, Hera Vlamakis, Clary B. Clish, Ramnik J. Xavier
Journal: Cell Host & Microbe (2019)
Sitting in Limbo — Obamacare under Divided Government
Authors: Jonathan Oberlander
Journal: New England Journal of Medicine (2019)

Interview with Dr. Jonathan Oberlander on the latest legal challenge to the Affordable Care Act and the ongoing health policy stalemate in Washington. (07:50)Download Even today, the Affordable Care Act remains in limbo. The Trump administration’s recent change of position on invalidating it underscores the ongoing conflict over health care reform. Yet the ensuing controversy illustrates the formidable barriers to overturning it.
Higher alveolar nitric oxide in COPD is related to poorer physical capacity and lower oxygen saturation after physical testing
Authors: Marieann Högman, Alexandra Thornadtsson, Kristina Bröms, Christer Janson, Karin Lisspers, Björn Ställberg, Hans Hedenström, Andrei Malinovschi
Journal: European Respiratory Journal (2019)

<b>Nitric oxide from the gas exchange area, but not from the airways, is increased in subjects with chronic obstructive pulmonary disease with low oxygen saturation after physical testing</b>http://bit.ly/2ItUJy6
The changing burden of long-term health outcomes in survivors of childhood acute lymphoblastic leukaemia: a retrospective analysis of the St Jude Lifetime Cohort Study
Authors: Daniel A Mulrooney, Geehong Hyun, Kirsten K Ness, Nickhill Bhakta, Ching-Hon Pui, Matthew J Ehrhardt, Kevin R Krull, Deborah B Crom, Wassim Chemaitilly, Deokumar K Srivastava, Mary V Relling, Sima Jeha, Daniel M Green, Yutaka Yasui, Leslie L Robison, Melissa M Hudson
Journal: The Lancet Haematology (2019)
Abstract P4-12-03: Prospective study: Impact of adjuvant chemotherapy with anthracyclines and taxanes in cognitive skills
Authors: SR Bella, AI Ferrari, MC Baiud, MN Cortes, JR Llugdar, ME Vigil
Journal: Cancer Research (2019)

Abstract Introduction Adjuvant chemotherapy is one of the outstanding treatments in the treatment of breast cancer. Many of its side effects are well known, while others are under study, as cognitive impairment. One/eight women have breast cancer, which often affects a young population. Cognitive disorders produced by chemotherapy were studied with controversial results. It seems convenient to study whether chemotherapy produces a cognitive impairment in a homogeneous group of patients receiving adjuvant chemotherapy with concomitant anthracycline cyclophosphamide followed by weekly paclitaxel (AC-T) in a prospective design. Methods Included patients had early-stage breast cancer (Stage I-II) and received AC-T (Anthracycline 60 mg/sqm - cyclophosphamide 600 mg/sqm and sequential weekly paclitaxel 80 mg/sqm) following surgery and before radiation therapy, as indicated. Her 2 positive patients also received adjuvant Trastuzumab therapy. The cognitive deficit was estimated through the Addenbrooke's Cognitive Examination test, taken the day of the beginning of treatment, and at 3, 6 and 12 months later. Beck Depression Inventory Test was used to assess depression. It was taken at the beginning of treatment and at 12 months later. Control group was built by healthy people, which were examined with the same test just once. Results From October 2016 to April 2014, 108 patients were included in chemotherapy group and 50 in a healthy control group. 51 patients completed 12 months follow up examination. Significant differences were found between patients and control group in attention, concentration, verbal fluency, language, visuospatial abilities and memory parameters. These parameters were found impaired at the beginning of the treatment, having a favorable evolution at twelve months, with a complete resolution. Orientation did not suffer significant changes during all study. 27/108 patients were found to be depressed at the beginning of treatment, with a favorable evolution of this parameter at twelve months. Control group did not suffer from any cognitive deficit or depression. Conclusions In this prospective study, patients suffered cognitive deterioration at the beginning of treatment, which was recovered at the twelve-month follow-up. Given the prevalence of depression in the chemotherapy group patients at the beginning of treatment versus the control group, this is probably the cause of the cognitive disorder. Citation Format: Bella SR, Ferrari AI, Baiud MC, Cortes MN, Llugdar JR, Vigil ME. Prospective study: Impact of adjuvant chemotherapy with anthracyclines and taxanes in cognitive skills [abstract]. In: Proceedings of the 2018 San Antonio Breast Cancer Symposium; 2018 Dec 4-8; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2019;79(4 Suppl):Abstract nr P4-12-03.
The clinical significance of interleukin‐6 in heart failure: results from the BIOSTAT‐CHF study
Authors: George Markousis‐Mavrogenis, Jasper Tromp, Wouter Ouwerkerk, Matt Devalaraja, Stefan D. Anker, John G. Cleland, Kenneth Dickstein, Gerasimos S. Filippatos, Pim van der Harst, Chim C. Lang, Marco Metra, Leong L. Ng, Piotr Ponikowski, Nilesh J Samani, Faiez Zannad, Aeilko H. Zwinderman, Hans L. Hillege, Dirk J. van Veldhuisen, Rahul Kakkar, Adriaan A. Voors, Peter van der Meer
Journal: European Journal of Heart Failure (2019)

Aims Inflammation is a central process in the pathophysiology of heart failure (HF), but trials targeting tumour necrosis factor (TNF)‐α were largely unsuccessful. Interleukin (IL)‐6 is an important inflammatory mediator and might constitute a potential pharmacologic target in HF. However, little is known regarding the association between IL‐6 and clinical characteristics, outcomes and other inflammatory biomarkers in HF. We thus aimed to identify and characterize these associations. Methods and results Interleukin‐6 was measured in 2329 patients [89.4% with a left ventricular ejection fraction (LVEF) ≤ 40%] of the BIOSTAT‐CHF cohort. The primary outcome was all‐cause mortality and HF hospitalization during 2 years, with all‐cause, cardiovascular (CV), and non‐CV death as secondary outcomes. Approximately half (56%) of all included patients had plasma IL‐6 values greater than the previously determined 95th percentile of normal values at baseline. Elevated N‐terminal pro‐brain natriuretic peptide, procalcitonin and hepcidin, younger age, TNF‐α/IL‐1‐related biomarkers, or having iron deficiency, atrial fibrillation and LVEF &gt; 40% independently predicted elevated IL‐6 levels. IL‐6 independently predicted the primary outcome [HR (95% confidence interval) per doubling: 1.16 (1.11–1.21), P &lt; 0.001], all‐cause mortality [1.22 (1.16–1.29), P &lt; 0.001] and CV as well as non‐CV mortality [1.16 (1.09–1.24), P &lt; 0.001; 1.31 (1.18–1.45), P &lt; 0.001], but did not improve discrimination in previously published risk models. Conclusions In a large, heterogeneous cohort of HF patients, elevated IL‐6 levels were found in more than 50% of patients and were associated with iron deficiency, reduced LVEF, atrial fibrillation and poorer clinical outcomes. These findings warrant further investigation of IL‐6 as a potential therapeutic target in specific HF subpopulations.
Brodalumab in the treatment of moderate to severe psoriasis in patients when previous anti-interleukin 17A therapies have failed
Authors: Grace Kimmel, Margot Chima, Hee Jin Kim, Jennifer Bares, Christopher J. Yao, Giselle Singer, Soo Jung Kim, Jerry Bagel, Mark Lebwohl
Journal: Journal of the American Academy of Dermatology (2019)
Reexamining visual cognition in human infants: On the necessity of representation
Authors: Matthew Schlesinger
Journal: Behavioral and Brain Sciences (2001)

The sensorimotor account of vision proposed by O'Regan &amp; Noë (O&amp;N) challenges the classical view of visual cognition as a process of mentally representing the world. Many infant cognition researchers would probably disagree. I describe the surprising ability of young infants to represent and reason about the physical world, and ask how this capacity can be explained in non-representational terms. As a first step toward answering this question, I suggest that recent models of embodied cognition may help illustrate a way of escaping the representational trap.
Useful apps for interpreting electrocardiograms: ECG Guide
Authors: Tom Lewis
Journal: BMJ (2012)

ECG Guide is a concise, authoritative reference that contains detailed information on electrocardiograms. The “book” has essential information required to understand and interpret an electrocardiogram. The app is comprehensive, with sections including ventricular/atrial enlargement, assessment of ischaemia, approach to arrhythmia, …
What is the point? Finding meaning in research for the current generation of medical students
Authors: Daniel J Mulder
Journal: BMJ (2012)

It is becoming more difficult to recruit and train clinician scientists. Although this is a multifaceted problem, I wonder if one of the root problems might be motivation. Many of us medical trainees perceive research as an unnecessary part of the medical curriculum. But such attitudes endanger the future of medical science.

The problem could derive in part from the fact that my generation sees the world differently from previous generations in many aspects that apply to research and medicine. We …
Abstract P1-11-13: Depomedroxyprogesterone therapy for hot flashes in survivors of ER-expressing breast cancer: Impact on recurrence and survival
Authors: N Ertz-Archambault, L Rogoff, H Kosiorek, B Ernst, K Anderson, B Pockaj, R Gray, D Northfelt
Journal: Cancer Research (2019)

Abstract Background Survivors of ER-expressing operable breast cancer (ER+BC) generally do not receive hormone replacement therapy for menopausal symptoms due to concern about provoking recurrence of disease. Single dose depomedroxyprogesterone acetate (MPA) 400 mg IM has previously been shown (Loprinzi CL, et al. J Clin Oncol 2006;24:1409) to be the most effective non-estrogen therapy available for menopausal hot flashes (HF) but long-term evidence of safety in survivors of ER+BC is lacking. Methods Consecutive patients previously diagnosed with ER+BC who received MPA for HF between January 2007 and December 2012 were retrospectively identified in the breast cancer patient database at Mayo Clinic Arizona. Medical records were audited for breast cancer outcomes in these cases and in contemporaneous control patients with ER+BC who did not receive MPA, matched for age, stage of disease, and year of diagnosis. Statistical comparisons of local-regional recurrence and event-free survival were performed. Results 92 patients who received MPA were identified and matched 1:1 with contemporaneous controls. Median follow-up duration was 5.7 years in cases and 4.5 years in controls. Estimated local-regional recurrence free survival at 10 years was 85% (95% CI, 72-100%) in cases and 95% (95% CI, 86-100%) in controls. Matched pairs hazard ratio was 1.0 (95% CI, 0.06-16.0) for local-regional recurrence free survival. Estimated event-free survival at 10 years was 81% (95% CI, 69-97%) in cases and 76% (95% CI, 64-92%) in controls. Matched pairs hazard ratio was 0.38 (95% CI, 0.10-1.41) for event-free survival. The majority (77%) of case patients experienced satisfactory relief of hot flashes from MPA injection. Conclusion In this retrospective case-control study we were unable to identify a detrimental effect of MPA therapy for HF in survivors of ER+BC. MPA may be acceptable for management of HF in this population. Citation Format: Ertz-Archambault N, Rogoff L, Kosiorek H, Ernst B, Anderson K, Pockaj B, Gray R, Northfelt D. Depomedroxyprogesterone therapy for hot flashes in survivors of ER-expressing breast cancer: Impact on recurrence and survival [abstract]. In: Proceedings of the 2018 San Antonio Breast Cancer Symposium; 2018 Dec 4-8; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2019;79(4 Suppl):Abstract nr P1-11-13.
Extracellular Volume Associates With Outcomes More Strongly Than Native or Post-Contrast Myocardial T1
Authors: Thomas A Treibel, Yaron Fridman, Patrick Bering, Aatif Sayeed, Maren Maanja, Fredrika Frojdh, Louise Niklasson, Eric Olausson, Timothy C Wong, Peter Kellman, Christopher A Miller, James C Moon, Martin Ugander, Erik B Schelbert
Journal: JACC. Cardiovascular imaging (2019)
Women and their weight
Authors: Isabella Laws
Journal: BMJ (2013)

The fact that many women have an obsession with being the “right” weight is hardly a revelation. But in her latest book, The Ministry of Being Thin , Emma Woolf discusses the various factors and industries that fuel our fascination with food, and our relationship with it. She says “we delay our lives, we put our happiness on hold, we tell ourselves how great everything will be when we’ve lost weight.” According to Woolf, our life choices in everything from sex to surgery are dictated by how we look, and how that in turn makes us feel. The book is able to offer …
Abstract TS3-2: Modulation of anti-tumor immunity using CDK4/6 inhibitors
Authors: S Goel
Journal: Cancer Research (2019)

Abstract Several pharmacological inhibitors of cyclin-dependent kinases 4 and 6 (CDK4/6) have now been approved for the treatment of metastatic estrogen receptor-positive breast cancer. Although CDK4/6 inhibitors were initially developed to prevent cancer cell proliferation, preclinical studies have now demonstrated that they can also exert other biological effects in solid tumors including augmentation of anti-tumor immunity. The detailed mechanisms underlying this are currently under investigation, and likely include enhanced antigen presentation by tumor cells as well as an increase in the ratio of effector to regulatory T lymphocytes. In this presentation, I will discuss our current understanding of how CDK4/6 inhibitors might stimulate anti-tumor immune responses, focusing on breast cancer. I will also discuss if and how this unexpected phenomenon might be leveraged for therapeutic benefit. Citation Format: Goel S. Modulation of anti-tumor immunity using CDK4/6 inhibitors [abstract]. In: Proceedings of the 2018 San Antonio Breast Cancer Symposium; 2018 Dec 4-8; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2019;79(4 Suppl):Abstract nr TS3-2.
Development of immune checkpoint therapy for cancer
Authors: Jill M. Fritz, Michael J. Lenardo
Journal: The Journal of Experimental Medicine (2019)

Since the early 20th century, immunologists have investigated mechanisms that protect vertebrates from damaging immune responses against self-antigens by mature lymphocytes, i.e., peripheral tolerance. These mechanisms have been increasingly delineated at the molecular level, ultimately culminating in new therapeutics that have revolutionized clinical oncology. Here, we describe basic science and clinical discoveries that converge mainly on two molecules, CTLA-4 and PD-1, that were recognized with the 2018 Nobel Prize in Physiology or Medicine awarded to James Allison and Tasuku Honjo. We discuss their investigations and those of many others in the field that contravene tolerance through checkpoint inhibition to boost immune killing of malignant cells. We also discuss the mechanisms underlying each therapy, the efficacy achieved, and the complications of therapy. Finally, we hint at research questions for the future that could widen the success of cancer immunotherapy.
Making the most of Christmas
Authors: Katherine Bettany
Journal: BMJ (2013)

I have an unashamed love for Christmas. For many of you, it will mean a short break and time to catch up with family and friends, on sleep, and other happiness restoring activities that easily get put aside during term time. For me, it also means a chance to watch my favourite Christmas film— Home Alone —over and over. If you feel compelled to learn something, though, why not watch or read the books and films we’ve suggested (doi:10.1136/sbmj.f7459), which all have a medical theme. It’s like revision, but …
Abstract 4741: Application of nanotechnology for enhanced early detection of prostate cancer in African-American men
Authors: Catherine M Phelan, Sergei Ostapenko, Anna Chornokur, Richard Tanner, jin zhang, Julio Pow-Sang, John Jack Steel, Thomas Sellers
Journal: Cancer Research (2008)

Abstract Background: African American men in the US have the highest incidence and mortality from prostate cancer in the world. Five-year survival rates are almost 100% of African American men diagnosed with early stage prostate cancer but only 29% for men diagnosed in the late stages of the disease. Early detection is thus the key to improved mortality and morbidity. We are investigating nanotechnologies to enhance the detection of prostate cancer biomarkers at extremely low levels in blood serum. Our goal is to engineer a multi-biomarker panel that will provide sufficiently high sensitivity and specificity such that it can be applied as a screening test and decrease prostate cancer morbidity and mortality among African-American men. Objectives: 1.To engineer quantum dot - antibody conjugates targeting established prostate cancer biomarkers (antigens): prostate specific antigen (PSA), Kallikrein 2 (KLK2), Kallikrein 14 (KLK14), Osteoprotegerin (OPG), Antip53Ab, Caveolin-1 (Cav-1) and Interleukin-6 (IL-6) 2. To define the photoluminescence signatures of bound versus unbound QDs, reflecting antigen-antibody complex formation. 3. To derive optimal cutpoints for the sensitivity and specificity of the novel QD-conjugated biomarkers individually, and in combination, for the early detection of prostate cancer in African-American men. Results: We have established an African American prostate cancer case-control collection. We have successfully conjugated antibodies to the above biomarkers to quantum dots and these are undergoing characterization. We have observed that the bio-conjugated QD shows a spectral shift of the maximum position on average by 4 nm in comparison to non-conjugated QDs. The shift is towards a shorter wavelengths “blue” shift for conjugated quantum dots. Its existence was confirmed with repetition of the conjugation scheme with identical parameters and the “blue” shift was observed in all repeated experiments. The PL spectral shift observed on bio-conjugated QDs with antigens may be attributed to the existence of an external local electric field that is imposed by the surrounding biomolecules (Stark effect). The shift varied depending on the different antibodies attached and on QDs of different wavelengths. Conclusions: We have observed a spectral shift of the bio-conjugated quantum dots compared to unconjugated quantum dots. The benefit of this observation may lie in the fact that the shift is different for each antibody, thus will show a peak at different wavelengths. This effect may provide a powerful tool for multiplexing proteins for early cancer detection. This study has enormous potential impact on improved detection of this disease in the early and more curable stage which in turn would lead to decreased morbidity and mortality.
Daily Aspirin Use Associated With Reduced Risk For Fibrosis Progression In Patients With Nonalcoholic Fatty Liver Disease
Authors: Tracey G. Simon, Jacqueline Henson, Stephanie Osganian, Ricard Masia, Andrew T. Chan, Raymond T. Chung, Kathleen E. Corey
Journal: Clinical Gastroenterology and Hepatology (2019)