tbuckley/cabot-search huggingface dataset:
Emergence of immunoregulatory Ym1 <sup>+</sup> Ly6C <sup>hi</sup> monocytes during recovery phase of tissue injury
Authors: Naoki Ikeda, Kenichi Asano, Kenta Kikuchi, Yoshimi Uchida, Hiroki Ikegami, Ryo Takagi, Satoshi Yotsumoto, Takumi Shibuya, Chieko Makino-Okamura, Hidehiro Fukuyama, Takashi Watanabe, Masaki Ohmuraya, Kimi Araki, Gen Nishitai, Masato Tanaka
Journal: Science Immunology (2018)

Ly6Chi monocytes migrate to injured sites and induce inflammation in the acute phase of tissue injury. However, once the causes of tissue injury are eliminated, monocyte-derived macrophages contribute to the resolution of inflammation and tissue repair. It remains unclear whether the emergence of these immunoregulatory macrophages is attributed to the phenotypic conversion of inflammatory monocytes in situ or to the recruitment of bone marrow-derived regulatory cells de novo. Here, we identified a subpopulation of Ly6Chi monocytes that contribute to the resolution of inflammation and tissue repair. Ym1+Ly6Chi monocytes greatly expanded in bone marrow during the recovery phase of systemic inflammation or tissue injury. Ym1+Ly6Chi monocytes infiltrating into an injured site exhibited immunoregulatory and tissue-reparative phenotypes. Deletion of Ym1+Ly6Chi monocytes resulted in delayed recovery from colitis. These results demonstrate that a distinct monocyte subpopulation destined to act in immunoregulation is generated in bone marrow and participates in resolution of inflammation and tissue repair.
Prognostic value of the Breslow:diameter ratio in cutaneous melanoma
Authors: Antonio Piñero-Madrona, Alvaro Jesús Goméz-Ruiz, Guadalupe Ruiz-Merino, Enrique Martínez-Barba, Pablo Cerezuela-Fuentes, José Neptuno Rodríguez-López, Juan Cabezas-Herrera
Journal: Journal of the American Academy of Dermatology (2018)
Effects of dietary sterols on prostate cancer formation, progression and prevention
Authors: Yi Lu, Jun Zhang
Journal: Cancer Research (2007)

1650  Prostate cancer is the most frequently diagnosed malignancy and the second leading cause of cancer deaths in American men today. The discrepancy of prostate cancer incidence between males in Western societies and males in Asian countries correlates to the different dietary styles. We hypothesize that dietary animal and plant sterols may play critical roles in prostate cancer formation/progression, or prevention, respectively. To explore the possibility that cholesterol, the animal sterol, may promote, whereas plant sterols inhibit, prostate cancer formation and progression, we treated human prostate cancer cell lines (PC-3, DU145, LNCaP and C4-2B) with cholesterol or β-sitosterol (β-SIT), the major dietary plant sterol, and analyze the effects of dietary sterols on several parameters of tumor cells related to malignant progression, including proliferation, adhesion, migration and invasion. We found that in general cholesterol promoted prostate cancer cell proliferation, adhesion, migration and invasion ability. In contrast, β-sitosterol suppressed prostate cancer cell proliferation, migration and invasion, but had no or minor effects on adhesion (except for DU145). Specifically, cholesterol significantly promoted proliferation of prostate cancer cell line PC-3 (50.0% increase by comparing with the untreated control group), DU145 (62.5% increase), and LNCaP (31.1% increase), but only a minor promotion on C4-2B (4.2%); whereas β-sitosterol effectively suppressed proliferation of PC-3 (38.3% decrease by comparing with the untreated control group), DU145 (36.3% decrease), LNCaP (33.3% decrease) and C4-2B (60.0% decrease). In addition, by an in vitro invasion assay measuring cell penetration ability through matrigel, cholesterol promoted cell invasion ability of PC-3 (24.6% increase), DU145 (9.8% increase), LNCaP (58.8% increase) and C4-2B (37.0% increase); whereas β-sitosterol suppressed cell invasion ability of PC-3 (28.7% decrease), DU145 (86.8% decrease), LNCaP (41.2% decrease) and C4-2B (17.7% decrease). The potential mechanisms of how dietary sterols mediate promotion or inhibition of prostate cancer progression are also explored. These results suggest that consumption of plant sterol, a naturally present dietary nutrition, and reduction of cholesterol intake, will effectively prevent or retard prostate cancer formation and progression.  	This research project was supported by Cancer Research and Prevention Foundation grant and in part by NIH grant (DK65962).
Integration of gene expression and brain-wide connectivity reveals the multiscale organization of mouse hippocampal networks
Authors: Michael S. Bienkowski, Ian Bowman, Monica Y. Song, Lin Gou, Tyler Ard, Kaelan Cotter, Muye Zhu, Nora L. Benavidez, Seita Yamashita, Jaspar Abu-Jaber, Sana Azam, Darrick Lo, Nicholas N. Foster, Houri Hintiryan, Hong-Wei Dong
Journal: Nature Neuroscience (2018)
Cigarette smoke and HIV synergistically affect lung pathology in cynomolgus macaques
Authors: Hitendra S. Chand, Rodrigo Vazquez-Guillamet, Christopher Royer, Karin Rudolph, Neerad Mishra, Shashi P. Singh, Shah S. Hussain, Edward Barrett, Shannon Callen, Siddappa N. Byrareddy, Maria Cristina Vazquez Guillamet, Jawad Abukhalaf, Aryaz Sheybani, Vernat Exil, Veena Raizada, Hemant Agarwal, Madhavan Nair, Francois Villinger, Shilpa Buch, Mohan Sopori
Journal: Journal of Clinical Investigation (2018)

In the era of combined antiretroviral therapy (cART), lung diseases such as chronic bronchitis (CB) and chronic obstructive pulmonary disease (COPD) are common among persons living with HIV (PLWH), particularly smokers. Although smoking is highly prevalent among PLWH, HIV may be an independent risk factor for lung diseases; however, the role of HIV and cigarette smoke (CS) and their potential interaction in the development of chronic lung diseases among PLWH has not been delineated. To investigate this interaction, cynomolgus macaques were exposed to CS and/or simian-adapted human immunodeficiency virus (SHIV) and treated with cART. The development of CB and the lung functions were evaluated following CS±SHIV treatment. The results showed that in the lung, SHIV was a strong independent risk factor for goblet cell metaplasia/hyperplasia and mucus formation, MUC5AC synthesis, loss of tight junction proteins, and increased expression of Th2 cytokines/transcription factors. In addition, SHIV and CS synergistically reduced lung function and increased extrathoracic tracheal ring thickness. Interestingly, SHIV infection generated significant numbers of HIV-gp120+ epithelial cells (HGECs) in small airways and alveoli, and their numbers doubled in CS+SHIV-infected lungs. We conclude that even with cART, SHIV independently induces CB and pro-COPD changes in the lung, and the effects are exacerbated by CS.
Abstract 9941: Baseline Vitamin D Levels, Vitamin D Deficiency and Changes in Vitamin D With Statin Therapy Do Not Predict Statin Myalgia
Authors: Beth Taylor, Heather Swales, Lindsay Lorson, C. Michael White, Paul D Thompson
Journal: Circulation (2015)

Background and Objective: Low Vitamin D levels have been implicated as contributing to statin myalgia, but studies on the relationship between Vitamin D and statin-associated muscle side effects (SAMS) have produced discrepant results. We examined the influence of baseline and change in Vitamin D levels in patients with self-reported statin myalgia who developed muscle symptoms during a statin-placebo cross-over trial. Methods: Statin myalgia was verified in 120 patients with prior statin muscle complaints using an 8-week randomized, double-blind crossover trial of simvastatin (SIMVA) 20 mg/d and placebo. Anthropometrics, medical histories, demographics and serologic data (including 25 (OH)Vitamin D) were measured at each phase of the trial. Results: Forty three (35.8%) patients met the study criteria for myalgia, experiencing muscle pain on SIMVA but not placebo. Serum Vitamin D levels (mean ± standard deviation) prior to simvastatin treatment were not different between patients who did (31.7 ±12.1 ng/mL) or did not (31.6 ±10.3 ng/mL) develop myalgia and did not predict SAMS (r 2 = 0.00; p = 0.96). The change in Vitamin D with SIMVA (post-pre treatment) was also not different between myalgic and non-myalgic patients (0.3 ± 5.9 vs. 0.2 ±8.3 ng/mL, respectively) and again did not predict SAMS (r 2 = 0.00; p = 0.96). In addition, the proportion of patients classified as Vitamin D deficient (&lt; 20 ng/mL) did not differ between myalgics and non-myalgics (n=7 vs. n=8; χ 2 =1.45; p = 0.23), nor did the proportion of patients classified as Vitamin D insufficient (&lt; 30 ng/mL) (n=18 vs. n=37; χ 2 &lt; 0.01 and p = 0.94, respectively). Conclusions: Our results suggest that baseline levels of Vitamin D, Vitamin D deficiency/insufficiency and changes in Vitamin D with statin therapy do not predict statin myalgia in patients in whom SAMS are verified using a rigorous double-blind, cross-over study design. The failure to verify SAMS in other studies may explain the discordant results on Vitamin D as a risk factor and potential treatment for statin myalgia. Trial Registration: NCT01140308
Cardiovascular disease models: A game changing paradigm in drug discovery and screening
Authors: Houman Savoji, Mohammad Hossein Mohammadi, Naimeh Rafatian, Masood Khaksar Toroghi, Erika Yan Wang, Yimu Zhao, Anastasia Korolj, Samad Ahadian, Milica Radisic
Journal: Biomaterials (2018)

Cardiovascular disease is the leading cause of death worldwide. Although investment in drug discovery and development has been sky-rocketing, the number of approved drugs has been declining. Cardiovascular toxicity due to therapeutic drug use claims the highest incidence and severity of adverse drug reactions in late-stage clinical development. Therefore, to address this issue, new, additional, replacement and combinatorial approaches are needed to fill the gap in effective drug discovery and screening. The motivation for developing accurate, predictive models is twofold: first, to study and discover new treatments for cardiac pathologies which are leading in worldwide morbidity and mortality rates; and second, to screen for adverse drug reactions on the heart, a primary risk in drug development. In addition to in vivo animal models, in vitro and in silico models have been recently proposed to mimic the physiological conditions of heart and vasculature. Here, we describe current in vitro, in vivo, and in silico platforms for modelling healthy and pathological cardiac tissues and their advantages and disadvantages for drug screening and discovery applications. We review the pathophysiology and the underlying pathways of different cardiac diseases, as well as the new tools being developed to facilitate their study. We finally suggest a roadmap for employing these non-animal platforms in assessing drug cardiotoxicity and safety.
Abstract 17241: Conversion of Recurrent Arrhythmia by the Wearable Cardioverter-defibrillator
Authors: Steven Ringquist, Nicole R Bianco, Steven J Szymkiewicz
Journal: Circulation (2015)

Background: Sudden cardiac arrest (SCA) due to ventricular tachycardia (VT) or fibrillation (VF) reportedly reoccurs after an initial successful defibrillation in 60% or more of patients (pts). First responder programs have been associated with 25-71% return of spontaneous circulation (ROSC) and 73% survival to hospital admission when pts require additional, more than one, defibrillation treatment shock. Although VT/VF SCA occurring in wearable cardioverter defibrillator (WCD) pts has a 98% first shock success and 94% survival, the incidence and outcomes of recurrent VT/VF after an initial, successful shock is unknown. Methods: The ZOLL registry of WCD pts was used to identify 1,219 USA pts appropriately treated from Oct 2009 through Aug 2014. Pts were included if they met the following: Group A, 1 shock in response to a detection cycle triggered by a single VT/VF episode; Group B, 1 shock in response to the first of two consecutive detection cycles, and 1 or more appropriate shocks delivered in response to a second, recurring VT/VF episode. Results: There were 1,145 pts successfully converted with the first shock to VT/VF. Of these, 846 (74%) did not have VT/VF recurrence (Group A), while 299 (26%) were defibrillated again for recurrent VT/VF (Group B), with a median time between treatments of 71 minutes. Demographic and clinical characteristics of Group A and Group B differed only in the frequency of implantable cardioverter defibrillator explant pts (p&lt;.01), which was increased 2-fold in Group B. First shock efficacy among Group A was high with 97% conversion success and 92% acute survival observed. Among Group B pts the recurring VT/VF shock conversion (97%) and acute survival (92%) was not significantly different, and conversion success was independent of the elapsed time between episodes. Deaths in Group B were primarily associated with a shorter elapsed time (10 minutes or less) between new VT/VF episodes (Pearson’s correlation 0.99). Conclusions: A smaller fraction of WCD pts (26%) experience recurrent VT/VF than reported during first responder resuscitation. Conversion success of recurrent VT/VF among WCD pts was 97% and independent of the elapsed time between VT/VF episodes. SCA survival regardless of VT/VF recurrence was high, 92%.
Notes from the Field: Lead Exposures Among Employees at a Bullet Manufacturing Company — Missouri, 2017
Authors: David A. Jackson, Gregory A. Burr, Carol R. Braun, Marie A. de Perio
Journal: MMWR Morbidity and Mortality Weekly Report (2018)

In October 2017, at the request of a Missouri bullet manufacturing, CDCâs National Institute for Occupational Safety and Health conducted a health hazard evaluation to determine routes and extent of lead exposure. Their findings indicated elevated blood lead levels among almost all employees and air lead conentrations below federal guidelines and recommended a workplace lead control program be used.
SP0066 Biological dmard case presentation
Authors: J. Kedra
Journal: Annals of the Rheumatic Diseases (2018)

<h3></h3> We present the case of a male patient, who developped in 2002 (at the age of 37) rheumatoid arthritis, at that time positive for RF and ACPA without erosions on X-rays. He was first treated with salazopyrine, stopped in 2003 because of residual disease activity and structural damage progression on X-rays (MTP 5 erosion, JSN on both carpal joints), then methotrexate, which was efficient but was finally stopped in 2004 for suspicion of MTX pulmonary toxicity (cough, short breath, with CT-scan abnormality). Leflunomide 20 mg/day was started with adequate response up to 2009, when loss of efficacy was recorded. Addition of adalimumab 40 mg every other week was decided, leading to sustained remission. In 2011, he was on remission with this combination of treatments, and he stopped adalimumab abruptly on his own, resulting in a flare after 4 months (7 tender joints and 5 swollen joints). Adalimumab every other week was restarted, and remission was obtained a few weeks later. In 2013, he remained on sustained remission, which lead to his inclusion in a trial testing the progressive spacing of adalimumab. Every 6 months, the disease activity was assessed in consultation, and hands and feet X-rays were repeated every year: the patient remained on sustained remission according to DAS28, and there was no additional structural damage. Finally, in May 2017, DAS28 was at 1.71 with leflunomide 20 mg/day and adalimumab 40 mg every 2 months, so we proposed to stop adalimumab. When last seen, in November 2017, the patient was still on remission with leflunomide monotherapy. <h3>Disclosure of Interest</h3> None declared
Hypoglycemia and Elevated Troponin in Patients With Diabetes and Coronary Artery Disease
Authors: Paulo C. Rezende, Brendan M. Everett, Maria Mori Brooks, Helen Vlachos, Trevor J. Orchard, Robert L. Frye, Deepak L. Bhatt, Mark A. Hlatky
Journal: Journal of the American College of Cardiology (2018)
Efficacy and tolerability of a cocktail of bacteriophages to treat burn wounds infected by Pseudomonas aeruginosa (PhagoBurn): a randomised, controlled, double-blind phase 1/2 trial
Authors: Patrick Jault, Thomas Leclerc, Serge Jennes, Jean Paul Pirnay, Yok-Ai Que, Gregory Resch, Anne Françoise Rousseau, François Ravat, Hervé Carsin, Ronan Le Floch, Jean Vivien Schaal, Charles Soler, Cindy Fevre, Isabelle Arnaud, Laurent Bretaudeau, Jérôme Gabard
Journal: The Lancet Infectious Diseases (2018)
Presence of High-Intensity Sweeteners in Popular Cigarillos of Varying Flavor Profiles
Authors: Hanno C. Erythropel, Grace Kong, Tamara M. deWinter, Stephanie S. O’Malley, Sven E. Jordt, Paul T. Anastas, Julie B. Zimmerman
Journal: JAMA (2018)

Bridget K. Ambrose, PhD, MPH; Hannah R. Day, PhD; Brian Rostron, PhD; Kevin P. Conway, PhD; Nicolette Borek, PhD; Andrew Hyland, PhD; Andrea C. Villanti, PhD, MPH
Endothelial cell α-globin and its molecular chaperone α-hemoglobin–stabilizing protein regulate arteriolar contractility
Authors: Christophe Lechauve, Joshua T. Butcher, Abdullah Freiwan, Lauren A. Biwer, Julia M. Keith, Miranda E. Good, Hans Ackerman, Heather S. Tillman, Laurent Kiger, Brant E. Isakson, Mitchell J. Weiss
Journal: Journal of Clinical Investigation (2018)

Arteriolar endothelial cell–expressed (EC-expressed) α-globin binds endothelial NOS (eNOS) and degrades its enzymatic product, NO, via dioxygenation, thereby lessening the vasodilatory effects of NO on nearby vascular smooth muscle. Although this reaction potentially affects vascular physiology, the mechanisms that regulate α-globin expression and dioxygenase activity in ECs are unknown. Without β-globin, α-globin is unstable and cytotoxic, particularly in its oxidized form, which is generated by dioxygenation and recycled via endogenous reductases. We show that the molecular chaperone α-hemoglobin–stabilizing protein (AHSP) promotes arteriolar α-globin expression in vivo and facilitates its reduction by eNOS. In Ahsp−/− mice, EC α-globin was decreased by 70%. Ahsp−/− and Hba1−/− mice exhibited similar evidence of increased vascular NO signaling, including arteriolar dilation, blunted α1-adrenergic vasoconstriction, and reduced blood pressure. Purified α-globin bound eNOS or AHSP, but not both together. In ECs in culture, eNOS or AHSP enhanced α-globin expression posttranscriptionally. However, only AHSP prevented oxidized α-globin precipitation in solution. Finally, eNOS reduced AHSP-bound α-globin approximately 6-fold faster than did the major erythrocyte hemoglobin reductases (cytochrome B5 reductase plus cytochrome B5). Our data support a model whereby redox-sensitive shuttling of EC α-globin between AHSP and eNOS regulates EC NO degradation and vascular tone.
c-Myc directly regulates nucleotide metabolism
Authors: Mikhail Nikiforov, Michael Im, Dazhong Zhuang, Sudha Mannava, Vladimir Grachtchouk, Linda J. Wheeler, Christopher Mathews, Donna Shewach
Journal: Cancer Research (2008)

1682   To identify c-Myc targets rate-limiting for proliferation of tumor cells, we stably inhibited c-Myc in several human melanoma lines  via  lentivirus-based shRNAs approximately to the levels detected in normal melanocytes. c-Myc depletion resulted in the repression of several genes encoding enzymes rate-limiting for dNTP metabolism including thymidylate synthase (TS), inosine monophosphate dehydrogenase 2 (IMPDH2) and phosphoribosyl pyrophosphate synthetase 2 (PRPS2), reduction in the amounts of deoxyribonucleoside triphosphates (dNTPs) and inhibition of proliferation. Individual suppression of TS, IMPDH2 or PRPS2 via specific shRNAs resulted in the decrease of dNTP pools and inhibition of proliferation of melanoma cells, thus reproducing effects caused in these cells by depletion of c-Myc. Reciprocally, concurrent overexpression of cDNAs for TS, IMPDH2 and PRPS2 in melanoma cells delayed proliferative arrest caused by inhibition of c-Myc. Overexpression of c-Myc in normal melanocytes enhanced mRNA and protein expression of the above genes and increased dNTP pools. Chromatin immunoprecipitation confirmed that TS, IMPDH2 and PRPS2 genes are direct c-Myc targets. Our data establish a direct control of dNTP metabolism by c-Myc and identify the role of such control in proliferation of tumor cells.
CHARACTERIZATION OF RADIOTHERAPY-INDUCED CEREBRAL MICROBLEEDS WITH ULTRA-HIGH FIELD MRI: EXPERIENCE IN YOUNG AND ADULT BRAIN TUMOUR POPULATION
Authors: Melanie Morrison, Angela Jakary, Erin Felton, Christopher Hess, Jennifer Clarke, Nicholas Butowski, Susan Chang, Sabine Mueller, Janine Lupo
Journal: Neuro-Oncology (2018)
Exosomes: natural nanoparticles as bio shuttles for RNAi delivery
Authors: Saber Ghazizadeh Darband, Mohammad Mirza-Aghazadeh-Attari, Mojtaba Kaviani, Ainaz Mihanfar, Shirin Sadighparvar, Bahman Yousefi, Maryam Majidinia
Journal: Journal of Controlled Release (2018)
Abstract 15832: Survival and Clinical Characteristics of Atrial Fibrillation in Wild-type Transthyretin (ATTRwt) Cardiac Amyloidosis
Authors: Yuliya Mints, Gheorghe Doros, John L Berk, Lawreen Connors, Frederick L Ruberg
Journal: Circulation (2017)

Introduction: Wild-type transthyretin (ATTRwt) cardiac amyloidosis has emerged as an important cause of heart failure in the elderly. Atrial fibrillation (AF) also commonly affects older adults wit...
Abstract 18184: High-Sensitivity C-Reactive Protein Predicts the Risk of Sudden Cardiac Arrest in Ischemic Cardiomyopathy
Authors: Umesh C Sharma, Suraj Dahal, Milind Chaudhari, Changxing Ma, James Fallavollita, John M Canty
Journal: Circulation (2017)

Introduction: The most common modes of death in patients with ischemic cardiomyopathy are sudden cardiac arrest (SCA) or heart failure (HF). Currently, LV function is the only parameter identifying...
CQC-style inspections don’t raise standards or improve patient safety, say RCGP members
Authors: Gareth Iacobucci
Journal: BMJ (2018)

Inspections such as those carried out by the Care Quality Commission (CQC) are not effective in raising standards or ensuring patient safety, delegates at the Royal College of General Practitioners’ annual conference have argued.

The conference hosted a debate on the merits of inspection, in which Rebecca Payne, a GP and clinical adviser to the CQC, spoke in favour of the current regulatory model and Miles Mack, a Scottish GP, argued against.

After a passionate debate the delegates rejected a motion put forward by Payne that read, “This house believes that CQC-type inspection is an essential lever in raising standards and …
Use of topical rapamycin in the treatment of superficial lymphatic malformations
Authors: Pablo García-Montero, Javier del Boz, Eulalia Baselga-Torres, José Manuel Azaña-Defez, Manuel Alcaraz-Vera, Jesús Tercedor-Sánchez, Lucero Noguera-Morel, Ángel Vera-Casaño
Journal: Journal of the American Academy of Dermatology (2018)