tbuckley/cabot-search huggingface dataset:
Pro-inflammatory Aorta-Associated Macrophages Are Involved in Embryonic Development of Hematopoietic Stem Cells
Authors: Samanta Antonella Mariani, Zhuan Li, Siobhan Rice, Carsten Krieg, Stamatina Fragkogianni, Mark Robinson, Chris Sebastiaan Vink, Jeffrey William Pollard, Elaine Dzierzak
Journal: Immunity (2019)

Hematopoietic stem cells (HSCs) are generated from specialized endothelial cells of the embryonic aorta. Inflammatory factors are implicated in regulating mouse HSC development, but which cells in the aorta-gonad-mesonephros (AGM) microenvironment produce these factors is unknown. In the adult, macrophages play both pro- and anti-inflammatory roles. We sought to examine whether macrophages or other hematopoietic cells found in the embryo prior to HSC generation were involved in the AGM HSC-generative microenvironment. CyTOF analysis of CD45+ AGM cells revealed predominance of two hematopoietic cell types, mannose-receptor positive macrophages and mannose-receptor negative myeloid cells. We show here that macrophage appearance in the AGM was dependent on the chemokine receptor Cx3cr1. These macrophages expressed a pro-inflammatory signature, localized to the aorta, and dynamically interacted with nascent and emerging intra-aortic hematopoietic cells (IAHCs). Importantly, upon macrophage depletion, no adult-repopulating HSCs were detected, thus implicating a role for pro-inflammatory AGM-associated macrophages in regulating the development of HSCs.
Targeting peptide-decorated biomimetic lipoproteins improve deep penetration and cancer cells accessibility in solid tumor
Authors: Tao Tan, Yuqi Wang, Jing Wang, Zhiwan Wang, Hong Wang, Haiqiang Cao, Jie Li, Yaping Li, Zhiwen Zhang, Siling Wang
Journal: Acta Pharmaceutica Sinica B (2019)

The limited penetration of nanoparticles and their poor accessibility to cancer cell fractions in tumor remain essential challenges for effective anticancer therapy. Herein, we designed a targeting peptide-decorated biomimetic lipoprotein (termed as BL-RD) to enable their deep penetration and efficient accessibility to cancer cell fractions in a tumor, thereby improving the combinational chemo-photodynamic therapy of triple negative breast cancer. BL-RD was composed of phospholipids, apolipoprotein A1 mimetic peptide (PK22), targeting peptide-conjugated cytotoxic mertansine (RM) and photodynamic agents of DiIC18(5) (DiD). The counterpart biomimetic lipoprotein system without RM (termed as BL-D) was fabricated as control. Both BL-D and BL-RD were nanometer-sized particles with a mean diameter of less than 30 nm and could be efficiently internalized by cancer cells. After intravenous injection, they can be specifically accumulated at tumor sites. When comparing to the counterpart BL-D, BL-RD displayed superior capability to permeate across the tumor mass, extravasate from tumor vasculature to distant regions and efficiently access the cancer cell fractions in a solid tumor, thus producing noticeable depression of the tumor growth. Taken together, BL-RD can be a promising delivery nanoplatform with prominent tumor-penetrating and cancer cells-accessing capability for effective tumor therapy.
Mobility and self-care trajectories for individuals with cerebral palsy (aged 1–21 years): a joint longitudinal analysis of cohort data from the Netherlands and Canada
Authors: Dirk-Wouter Smits, Jan Willem Gorter, Corinne A Riddell, Jeanine M Voorman, Peter L Rosenbaum, Robert J Palisano, Stephen D Walter, Steven E Hanna, Leontien van Wely, Marjolijn Ketelaar
Journal: The Lancet Child & Adolescent Health (2019)
Abstract 15311: Noninvasive and Instantaneous Diagnostics of Acute Myocardial Infarction Using Intrinsic Frequency Method
Authors: Niema M Pahlevan, Wangde Dai, Robert A Kloner
Journal: Circulation (2018)

Introduction: Acute myocardial ischemia and infarction diagnosis is traditionally based on clinical (e.g. pain) and ECG criteria. Other advanced diagnostic techniques have limitations including inv...
Multiple adverse outcomes following first discharge from inpatient psychiatric care: a national cohort study
Authors: Florian Walter, Matthew J Carr, Pearl L H Mok, Sussie Antonsen, Carsten B Pedersen, Louis Appleby, Seena Fazel, Jenny Shaw, Roger T Webb
Journal: The Lancet Psychiatry (2019)

Discharged psychiatric inpatients are at elevated risk of serious adverse outcomes, but no previous study has comprehensively examined an array of multiple risks in a single cohort.
The Next Stage of Buprenorphine Care for Opioid Use Disorder
Authors: Herbert Malinoff
Journal: Annals of Internal Medicine (2019)

Letters4 June 2019The Next Stage of Buprenorphine Care for Opioid Use DisorderHerbert Malinoff, MDHerbert Malinoff, MDUniversity of Michigan, Ypsilanti, Michigan (H.M.)Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/L19-0141 SectionsAboutFull TextPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail TO THE EDITOR:How upsetting. The conflict-of-interest information at the end of Martin and colleagues' article (1) indicates that it was funded by CleanSlate Addiction Treatment Centers. In 2016, this organization settled with the U.S. Drug Enforcement Administration to avoid prosecution for fraudulent buprenorphine prescribing.Is this article “fake news”? Does Annals have any editorial judgment? What peer-review process took place?This article has reinforced my decision to cancel my membership in the American College of Physicians and my subscription to Annals.Reference1. Martin SA, Chiodo LM, Bosse JD, Wilson A. The next stage of buprenorphine care for opioid use disorder. Ann Intern Med. 2018;169:628-35. [PMID: 30357262]. doi:10.7326/M18-1652 LinkGoogle Scholar Author, Article, and Disclosure InformationAffiliations: University of Michigan, Ypsilanti, Michigan (H.M.)Disclosures: The author has disclosed no conflicts of interest. The form can be viewed at www.acponline.org/authors/icmje/ConflictOfInterestForms.do?msNum=L19-0141. PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetailsSee AlsoThe Next Stage of Buprenorphine Care for Opioid Use Disorder Stephen A. Martin , Lisa M. Chiodo , Jordon D. Bosse , and Amanda Wilson The Next Stage of Buprenorphine Care for Opioid Use Disorder Barbara Scolnick The Next Stage of Buprenorphine Care for Opioid Use Disorder Robert Sherrick The Next Stage of Buprenorphine Care for Opioid Use Disorder Mark H. Duncan , Anna D. Ratzliff , Diane M. Powers , Caleb J. Banta-Green , and Andrew J. Saxon The Next Stage of Buprenorphine Care for Opioid Use Disorder Stephen A. Martin , Lisa M. Chiodo , Jordon D. Bosse , and Amanda Wilson Metrics 4 June 2019Volume 170, Issue 11Page: 819KeywordsConflicts of interestDisclosureDrug administrationDrugsOpioid addiction ePublished: 4 June 2019 Issue Published: 4 June 2019 Copyright & PermissionsCopyright © 2019 by American College of Physicians. All Rights Reserved.PDF downloadLoading ...
Treatment-Related Toxicity Using Prostate-Only Versus Prostate and Pelvic Lymph Node Intensity-Modulated Radiation Therapy: A National Population-Based Study
Authors: Matthew G. Parry, Arunan Sujenthiran, Thomas E. Cowling, Julie Nossiter, Paul Cathcart, Noel W. Clarke, Heather Payne, Jan van der Meulen, Ajay Aggarwal
Journal: Journal of Clinical Oncology (2019)

There is a debate about the effectiveness and toxicity of pelvic lymph node (PLN) irradiation for the treatment of men with high-risk prostate cancer. This study compared the toxicity of intensity-modulated radiation therapy (IMRT) to the prostate and the pelvic lymph nodes (PPLN-IMRT) with prostate-only IMRT (PO-IMRT).
What should we do about vaccine hesitancy?
Authors: Fiona Godlee
Journal: BMJ (2019)

With the resurgence of measles—a disease we thought had been all but conquered—gaps in vaccination coverage are gaining increasing public attention. If vaccination rates continue their downward trajectory measles may once again become endemic. What should we do in the face of growing “vaccine hesitancy,” now listed as one of the World Health Organization’s 10 threats to global health (www.who.int/emergencies/ten-threats-to-global-health-in-2019)? Should we blame the parents, censor social media, enforce vaccination through school exclusion, or penalise non-vaccination through fines or loss of benefits?

These are just some of the approaches …
Abstract 18115: Are State Policies to Permit Pre-hospital Bypass Associated With Better Treatment Patterns Among Patients With ST-Elevation Myocardial Infarction? A Report From AHA's Mission: Lifeline Program
Authors: Jacqueline L Green, Alice K Jacobs, DaJuanicia N Simon, Karen Chiswell, Rosalia Blanco, Eric R Bates, William French, Douglas F Kupas, Greg Mears, Matthew Roe, Brahmajee K Nallamothu
Journal: Circulation (2015)

Introduction: Early success with regionalization of STEMI care has led many states to adopt statewide pre-hospital STEMI destination policies, allowing emergency medical services (EMS) to bypass non-PCI capable hospitals. The association with adoption of these policies and patterns of care among STEMI patients is unknown. Hypothesis: Compared with similar states without STEMI bypass policies, we hypothesized states with bypass policies would have a higher proportion of eligible STEMI patients 1) arrive by direct EMS transport to PCI hospitals (less transfer-in); 2) receive any reperfusion; and 3) receive timely PCI. Methods: Using data from Jan 1, 2013 to Dec 31, 2014 from the NCDR ACTION Registry, six states with bypass policies (cases) were matched to six states without bypass policies (controls) a priori on region, hospital density, and percent state participation in the registry. Using the matched sample, logistic regression models were adjusted for patient- and state-level characteristics. Outcomes were: 1) transfer-in status, 2) receipt of reperfusion, and 3) receipt of timely PCI. Results: Case states: Delaware, Iowa, Maryland, North Carolina, Pennsylvania, and Massachusetts, were matched to the respective control states: South Carolina, Minnesota, Virginia, Texas, New York and Connecticut, with 19,287 patients at 379 sites. Patients from states with bypass policies were similar in age, gender, and comorbidities to patients from states without bypass policies. They were more likely to be white, have private insurance, and reside in rural areas. They were less likely to transfer into a PCI hospital (aOR=0.60, 95% CI 0.26-1.35) and more likely to receive reperfusion therapy (aOR=1.77, 95% CI 0.96-3.24), but these trends were not statistically significant. They were also significantly more likely to receive primary PCI within 90 minutes (aOR=1.59, 95% CI 1.19-2.12) or 120 minutes (aOR=1.44, 95% CI 1.06-1.95) of first medical contact. Conclusions: Statewide adoption of STEMI destination policies allowing EMS to bypass non-PCI capable facilities is associated with shorter time from first medical contact to PCI and non-significant trends toward increased arrival by direct EMS transport and more receipt of reperfusion therapy.
Regional Heterogeneity in Gene Expression, Regulation, and Coherence in the Frontal Cortex and Hippocampus across Development and Schizophrenia
Authors: Leonardo Collado-Torres, Emily E. Burke, Amy Peterson, JooHeon Shin, Richard E. Straub, Anandita Rajpurohit, Stephen A. Semick, William S. Ulrich, Amanda J. Price, Cristian Valencia, Ran Tao, Amy Deep-Soboslay, Thomas M. Hyde, Joel E. Kleinman, Daniel R. Weinberger, Andrew E. Jaffe
Journal: Neuron (2019)
Bawa-Garba: “At rock bottom I had to remember why I wanted to be a doctor”
Authors: Elisabeth Mahase
Journal: BMJ (2019)

We need to focus on learning and changing, and if we go down a criminal route we will only create a blame culture, Hadiza Bawa-Garba told the Risky Business conference in London this week.

The trainee paediatrician’s words echoed the newly published findings of the independent review of medical manslaughter cases in the UK, commissioned by the GMC in response to the Bawa-Garba case, which has called for root and branch reform to ensure a “learning not blame” culture that was fair to patients and doctors.1

Bawa-Garba, who appeared through a video link, spoke about going through the current system and the fear that almost overwhelmed her.



Hadiza Bawa-Garba: “If I can serve humanity and have the tools to do that, then I should keep doing it. It’s almost a privilege to practise medicine

Press Association

Describing what it was like to appear in the dock as a defendant in a criminal court, she said, “I waited for the prosecution to …
Five-Year Outcomes with Dabrafenib plus Trametinib in Metastatic Melanoma
Authors: Caroline Robert, Jean J. Grob, Daniil Stroyakovskiy, Boguslawa Karaszewska, Axel Hauschild, Evgeny Levchenko, Vanna Chiarion Sileni, Jacob Schachter, Claus Garbe, Igor Bondarenko, Helen Gogas, Mario Mandalá, John B.A.G. Haanen, Celeste Lebbé, Andrzej Mackiewicz, Piotr Rutkowski, Paul D. Nathan, Antoni Ribas, Michael A. Davies, Keith T. Flaherty, Paul Burgess, Monique Tan, Eduard Gasal, Maurizio Voi, Dirk Schadendorf, Georgina V. Long
Journal: New England Journal of Medicine (2019)

Patients who have unresectable or metastatic melanoma with a BRAF V600E or V600K mutation have prolonged progression-free survival and overall survival when receiving treatment with BRAF inhibitors plus MEK inhibitors. However, long-term clinical outcomes in these patients remain undefined. To determine 5-year survival rates and clinical characteristics of the patients with durable benefit, we sought to review long-term data from randomized trials of combination therapy with BRAF and MEK inhibitors.
Evidence for Network-Based Cortical Thickness Reductions in Schizophrenia
Authors: Cassandra M.J. Wannan, Vanessa L. Cropley, M. Mallar Chakravarty, Chad Bousman, Eleni P. Ganella, Jason M. Bruggemann, Thomas W. Weickert, Cynthia Shannon Weickert, Ian Everall, Patrick McGorry, Dennis Velakoulis, Stephen J. Wood, Cali F. Bartholomeusz, Christos Pantelis, Andrew Zalesky
Journal: American Journal of Psychiatry (2019)

Cortical thickness reductions in schizophrenia are irregularly distributed across multiple loci. The authors hypothesized that cortical connectivity networks would explain the distribution of cortical thickness reductions across the cortex, and, specifically, that cortico-cortical connectivity between loci with these reductions would be exceptionally strong and form an interconnected network. This hypothesis was tested in three cross-sectional schizophrenia cohorts: first-episode psychosis, chronic schizophrenia, and treatment-resistant schizophrenia.Structural brain images were acquired for 70 patients with first-episode psychosis, 153 patients with chronic schizophrenia, and 47 patients with treatment-resistant schizophrenia and in matching healthy control groups (N=57, N=168, and N=54, respectively). Cortical thickness was compared between the patient and respective control groups at 148 regions spanning the cortex. Structural connectivity strength between pairs of cortical regions was quantified with structural covariance analysis. Connectivity strength between regions with cortical thickness reductions was compared with connectivity strength between 5,000 sets of randomly chosen regions to establish whether regions with reductions were interconnected more strongly than would be expected by chance.Significant (false discovery rate corrected) and widespread cortical thickness reductions were found in the chronic schizophrenia (79 regions) and treatment-resistant schizophrenia (106 regions) groups, with more circumscribed reductions in the first-episode psychosis group (34 regions). Cortical thickness reductions with the largest effect sizes were found in frontal, temporal, cingulate, and insular regions. In all cohorts, both the patient and healthy control groups showed significantly increased structural covariance between regions with cortical thickness reductions compared with randomly selected regions.Brain network architecture can explain the irregular topographic distribution of cortical thickness reductions in schizophrenia. This finding, replicated in three distinct schizophrenia cohorts, suggests that the effect is robust and independent of illness stage.
Annual Out-of-Pocket Expenditures and Financial Hardship Among Cancer Survivors Aged 18–64 Years — United States, 2011–2016
Authors: Donatus U. Ekwueme, Jingxuan Zhao, Sun Hee Rim, Janet S. de Moor, Zhiyuan Zheng, Jaya S. Khushalani, Xuesong Han, Erin E. Kent, K. Robin Yabroff
Journal: MMWR Morbidity and Mortality Weekly Report (2019)

In the United States in 2019, an estimated 16.9 million persons are living after receiving a cancer diagnosis (1). These cancer survivors face many challenges, including functional limitations, serious psychological distress (2), and other lasting and late effects of cancer treatments. Because of the high cost of cancer therapy, many cancer survivors are more likely to face substantial out-of-pocket health care expenditures and financial hardship, compared with persons without a history of cancer (3,4). Out-of-pocket expenditures and financial hardship associated with cancer have been higher among survivors aged 18-64 years than they have been among older survivors (5). To estimate annual out-of-pocket expenditures and financial hardship among cancer survivors aged 18-64 years, compared with persons without a cancer history, CDC, the American Cancer Society, and the National Cancer Institute analyzed data from the 2011-2016 Medical Expenditure Panel Survey (MEPS).* The average annual out-of-pocket spending per person was significantly higher among cancer survivors ($1,000; 95% confidence interval [CI] = $886-$1,113) than among persons without a cancer history ($622; CI = $606-$639). Financial hardship was common; 25.3% of cancer survivors reported material hardship (e.g., problems paying medical bills), and 34.3% reported psychological hardship (e.g., worry about medical bills). These findings add to accumulating evidence documenting the financial difficulties of many cancer survivors. Mitigating the negative impact of cancer in the United States will require implementation of strategies aimed at alleviating the disproportionate financial hardship experienced by many survivors. These strategies include systematic screening for financial hardship at cancer diagnosis and throughout cancer care, integration of discussions about the potential for adverse financial consequences of treatments in shared treatment decision-making, and linkage of patients and survivors to available resources to ensure access to high-quality evidence-based care.
Use of Peripherally Inserted Central Catheters in Patients With Advanced Chronic Kidney Disease
Authors: David Paje, Mary A.M. Rogers, Anna Conlon, Scott A. Flanders, Steven J. Bernstein, Vineet Chopra
Journal: Annals of Internal Medicine (2019)

Background: Existing guidelines, including Choosing Wisely recommendations, endorse avoiding placement of peripherally inserted central catheters (PICCs) in patients with chronic kidney disease (CKD). Objective: To describe the frequency of and characteristics associated with PICC use in hospitalized patients with stage 3b or greater CKD (glomerular filtration rate [GFR] <45 mL/min/1.73 m2). Design: Prospective cohort study. Setting: 52 hospitals participating in the Michigan Hospital Medicine Safety Consortium. Participants: Hospitalized medical patients who received a PICC between November 2013 and September 2016. Measurements: Percentage of patients receiving PICCs who had CKD, frequency of PICC-related complications, and variation in the proportion of PICCs placed in patients with CKD. Results: Of 20 545 patients who had PICCs placed, 4743 (23.1% [95% CI, 20.9% to 25.3%]) had an estimated GFR (eGFR) less than 45 mL/min/1.73 m2 and 699 (3.4%) were receiving hemodialysis. In the intensive care unit (ICU), 30.9% (CI, 29.7% to 32.2%) of patients receiving PICCs had an eGFR less than 45 mL/min/1.73 m2; the corresponding percentage in wards was 19.3% (CI, 18.8% to 19.9%). Among patients with an eGFR less than 45 mL/min/1.73 m2, multilumen PICCs were placed more frequently than single-lumen PICCs. In wards, PICC-related complications occurred in 15.3% of patients with an eGFR less than 45 mL/min/1.73 m2 and in 15.2% of those with an eGFR of 45 mL/min/1.73 m2 or higher. The corresponding percentages in ICU settings were 22.4% and 23.9%. In patients with an eGFR less than 45 mL/min/1.73 m2, PICC placement varied widely across hospitals (interquartile range, 23.7% to 37.8% in ICUs and 12.8% to 23.7% in wards). Limitation: Nephrologist approval for placement could not be determined, and 2.7% of eGFR values were unknown and excluded. Conclusion: In this sample of hospitalized patients who received PICCs, placement in those with CKD was common and not concordant with clinical guidelines. Primary Funding Source: Blue Cross Blue Shield of Michigan and Blue Care Network.
Abstract 15385: Challenges Encountered in the Pediatric Heart Network Echocardiogram Z-Score Study
Authors: Dongngan Truong, Leo Lopez, Peter Frommelt, Brenda Ni, Meryl Cohen, Ashwin Prakash, Steven Colan, Christopher Spurney, Jonathan Soslow, Gail Pearson, Joseph Mahgerefteh, Ritu Sachdeva, Ricardo Pignatelli, Felicia Trachtenberg, Mario Stylianou, Karen Altmann, Kathleen Ash, Joseph Camarda, Shahryar Chowdhury, Andreea Dragulescu, Michele Frommelt, Olukayode Garuba, Brian Soriano, Shubhika Srivastava, Poonam Thankavel, Mary van der Velde, LuAnn Minich
Journal: Circulation (2018)

Introduction: The Pediatric Heart Network (PHN) Echo Z-score Study collected retrospective demographic and echo data from 3215 healthy children at 19 centers over 3 years. We sought to describe the...
Association of Changes in Heart Failure Treatment With Patients’ Health Status
Authors: Merrill Thomas, Yevgeniy Khariton, Gregg C. Fonarow, Suzanne V. Arnold, Larry Hill, Michael E. Nassif, Puza P. Sharma, Javed Butler, Laine Thomas, Carol I. Duffy, Adam D. DeVore, Adrian Hernandez, Nancy M. Albert, J. Herbert Patterson, Fredonia B. Williams, Kevin McCague, John A. Spertus
Journal: JACC Heart Failure (2019)