tbuckley/cabot-search huggingface dataset:
Abstract 421: Activated Cardiac Myofibroblasts Can Revert Back to Become Resident Fibroblasts Upon Injury Cessation
Authors: Onur Kanisicak, Jason Karch, Hadi Khalil, Bryan Maliken, Jeffery D Molkentin
Journal: Circulation Research (2016)

Resident cardiac fibroblasts (CFs) are potential therapeutic targets in treating heart failure given the prominent role that fibrosis plays in this disorder. CFs directly convert to myofibroblasts (MFs) with injury where they mediate both adaptive wound healing after acute myocardial infarction as well as long-standing fibrosis during chronic disease states. However, the fate of activated MFs after injury recovery or when an infarction scar is stabilized remains poorly understood, in part because the field has lacked a definitive strategy for identifying and tracing MFs and CFs in vivo. To address this issue we recently generated a novel mouse model that permits lineage tracing of all MFs in the heart after injury or stress stimulation, which we used to address the fate of MFs after injury resolution. MFs were lineage traced with a tamoxifen inducible periostin allele knockin of the MerCreMer cDNA (PostnMCM), with a Rosa26-eGFP dependent reporter. PostnMCM x R26-eGFP mice were transiently injured with the combined infusion of angiotensin II and phenylephrine (Ang/PE) for 2 weeks, during which time tamoxifen was also given to trace all newly formed MFs. Mice were then allowed to “rest” for 2 weeks or longer with no Ang/PE as the fibrotic response regressed, and the fate of the eGFP + cells was assessed. The data show that immediately after 2 weeks of Ang/PE infusion nearly all the eGFP+ periostin lineage-traced myofibroblasts were αSMA positive and have an activated myofibroblast gene expression profile. However, when the fibrotic response regressed weeks later, a number of periostin-lineage traced eGFP+ cells were still present in the heart and these cells showed a phenotypic and molecular reversion back to CFs with a loss of myofibroblast marker genes. These results suggest that CFs are very unique cell types that can differentiate to MFs then back again to resident CFs.
Abstract 16595: NAD+ Precursor Nicotinamide Riboside Alleviates Alcoholic Cardiomyopathy via Mitophagy Induction: A Novel SIRT3-PGAM5-FUNDC1 Axis
Authors: Sai Ma, Feng Cao, Jun Ren
Journal: Circulation (2017)

Nicotinamide riboside (NR) is widely used as a NAD+ precursor vitamin. Supplementation with NR has been shown to protect against metabolic and age-related diseases in mammals. However, the potentia...
Indoor allergen levels in settled airborne dust are higher in day‐care centers than at home
Authors: I. Sander, A. Lotz, H. D. Neumann, C. Czibor, A. Flagge, E. Zahradnik, M. Raulf
Journal: Allergy (2017)

Abstract Background Early‐life sensitization to indoor allergens predicts asthma development. The aim of this study was to compare allergen concentrations in day‐care centers ( DCC ) with those in private homes. Methods Settled airborne dust was collected 4 times a year from 20 German DCC (620 samples) and from the homes of children and day‐care workers (602 samples) using electrostatic dust collectors ( EDC ). The samples were analyzed with fluorescence enzyme immunoassays recognizing domestic mite allergens ( DM ), Fel d 1, Can f 1, and Mus m 1. Pet allergen thresholds that discriminate samples from homes with cats or dogs from those without were calculated using receiver‐operating characteristics. Influences on allergen levels were analyzed using multilevel models. Results Allergen loads were on average higher in DCC than in homes. In DCC , 96% of the samples were positive for DM , 95% for Can f 1, 90% for Fel d 1, and 83% for Mus m 1. In homes, 84% contained DM , 48.5% Can f 1, 33% Fel d 1, and 43% Mus m 1. The threshold level for homes with dogs was 75 ng/m² Can f 1 (96.8% sensitivity, 96% specificity), and the threshold level for homes with cats was 46 ng/m² Fel d 1 (92% sensitivity, 94.9% specificity). In DCC , Can f 1 and Fel d 1 loads were higher than these thresholds in 37% and 54% of the samples, respectively. Allergen levels were significantly influenced by the season and room type; however, carpets on floors had no influence. Conclusions Mite, mouse, cat, and dog allergens were mostly higher in DCC than in homes. Exposure to dog and cat allergens in DCC often reached levels of households with pets.
Median Time to Antiretroviral Therapy Initiation in a Cohort of Chinese Infants Born With HIV
Authors: Yan Zhao, Yuexin Wang, Ailing Wang, Jennifer M. McGoogan, Zunyou Wu
Journal: JAMA Pediatrics (2017)

A delayed start to antiretroviral therapy (ART) endangers the survival of HIV-infected infants and is a particular concern in resource-limited settings.In China, the health care system has dramatically scaled up its response to HIV, and as of 2012, immediate initiation of ART was recommended for all perinatally infected infants younger than 2 years. 1 This study aimed to assess outcomes for infants diagnosed with HIV from 2011 to 2015.Methods | The present study involves a nationwide cohort of infants reported to China's HIV/AIDS Comprehensive Re-sponse Information Management System (CRIMS), which contains information about all HIV cases in China. 2 However, CRIMS does not collect information on infant HIV testing dates, whether the tests were via serological vs virological methods, and CD4 percentage, because these data points fall under separate, specialized programs aimed at the prevention of mother-to-child transmission. 2,3The study protocol was approved by the institutional review board of the National Center for AIDS/STD Control and Prevention at the Chinese Center for Disease Control and Prevention.This study was exempt from informed consent procedures, because it is a secondary analysis of existing program data.
A randomized phase II study of bevacizumab versus bevacizumab plus lomustine versus lomustine single agent in recurrent glioblastoma: The Dutch BELOB study.
Authors: Walter Taal, Hendrika M Oosterkamp, Annemiek M.E. Walenkamp, Laurens Victor Beerepoot, Monique Hanse, J. Buter, Aafke Honkoop, Dolf Boerman, Filip Yves Francine Leon De Vos, Rob L. Jansen, Franchette W.P.J. van den Berkmortel, Dieta Brandsma, Johan M Kros, Jacoline E Bromberg, Irene van Heuvel, Marion Smits, Bronno van der Holt, Rene Vernhout, Martin J. Van Den Bent
Journal: Journal of Clinical Oncology (2013)

2001 Background: Bevacizumab (BEV) is widely used in recurrent glioblastoma, alone or in combination with other agents. There is however no well-controlled trial to support the use for this indication. Methods: In a three-arm Dutch multicenter randomized phase II study (NTR 1929) patients were assigned to either BEV 10 mg/kg iv every 2 weeks, BEV 10 mg/kg iv every 2 weeks and 110 mg/m 2 lomustine every 6 weeks, or lomustine 110 mg/m 2 every 6 weeks. Eligible were patients with histologically proven glioblastoma, with a first recurrence after chemo-irradiation with temozolomide, having concluded radiotherapy more than 3 months ago, with adequate bone marrow, renal and hepatic function, and WHO performance status (PS) 0-2. Primary endpoint was 9 months overall survival (OS); P 0 was set at 35% and P 1 at 55%. Progression was defined using RANO criteria. A safety review after the first 10 patients in the combination arm was preplanned. Results: Between December 2009 and November 2011, 153 patients were enrolled of whom 148 were considered eligible. Median age was 57 years (range, 24-77) and median WHO PS was 1. With respect to prognostic factors groups were well balanced. After review of the safety cohort the dosage lomustine in the combination arm was lowered to 90 mg/m 2 because of hematological toxicity (predominantly thrombocytopenia without symptoms). At this lower lomustine dose level the combination treatment was in general well tolerated. Outcome: see Table. Conclusions: In this first well-controlled study on BEV in recurrent glioblastoma with a primary OS endpoint, combination treatment with bevacizumab and lomustine met the prespecified criterion for further investigation in clinical trials, whereas both drugs given as single agent failed to meet this criterion. Clinical trial information: NTR1929. [Table: see text]
Identifying prognostic subgroups for outcomes in wild-type RAS metastatic colorectal cancer (mCRC) treated with anti-EGFR drugs
Authors: L. Vladimirova, O. Kit, N. Abramova, A. Storozhakova, I. Popova, N. Tikhanovskaya, M. Ezhova
Journal: Annals of Oncology (2017)
Enhancement of cutaneous immunity during aging by blocking p38 mitogen-activated protein (MAP) kinase–induced inflammation
Authors: Milica Vukmanovic-Stejic, Emma S. Chambers, Mayte Suárez-Fariñas, Daisy Sandhu, Judilyn Fuentes-Duculan, Neil Patel, Elaine Agius, Katie E. Lacy, Carolin T. Turner, Anis Larbi, Veronique Birault, Mahdad Noursadeghi, Neil A. Mabbott, Malcolm H.A. Rustin, James G. Krueger, Arne N. Akbar
Journal: Journal of Allergy and Clinical Immunology (2017)

Immunity decreases with age, which leads to reactivation of varicella zoster virus (VZV). In human subjects age-associated immune changes are usually measured in blood leukocytes; however, this might not reflect alterations in tissue-specific immunity.We used a VZV antigen challenge system in the skin to investigate changes in tissue-specific mechanisms involved in the decreased response to this virus during aging.We assessed cutaneous immunity based on the extent of erythema and induration after intradermal VZV antigen injection. We also performed immune histology and transcriptomic analyses on skin biopsy specimens taken from the challenge site in young (<40 years) and old (>65 years) subjects.Old human subjects exhibited decreased erythema and induration, CD4+ and CD8+ T-cell infiltration, and attenuated global gene activation at the site of cutaneous VZV antigen challenge compared with young subjects. This was associated with increased sterile inflammation in the skin in the same subjects related to p38 mitogen-activated protein kinase-related proinflammatory cytokine production (P < .0007). We inhibited systemic inflammation in old subjects by means of pretreatment with an oral small-molecule p38 mitogen-activated protein kinase inhibitor (Losmapimod; GlaxoSmithKline, Brentford, United Kingdom), which reduced both serum C-reactive protein levels and peripheral blood monocyte secretion of IL-6 and TNF-α. In contrast, cutaneous responses to VZV antigen challenge were increased significantly in the same subjects (P < .0003).Excessive inflammation in the skin early after antigen challenge retards antigen-specific immunity. However, this can be reversed by inhibition of inflammatory cytokine production that can be used to promote vaccine efficacy and the treatment of infections and malignancy during aging.
Payment Reform to Enhance Collaboration of Primary Care and Cardiology
Authors: Steven A. Farmer, Paul N. Casale, Linda D. Gillam, John S. Rumsfeld, Shari Erickson, Neil M. Kirschner, Kevin de Regnier, Bruce R. Williams, R. Shawn Martin, Mark B. McClellan
Journal: JAMA Cardiology (2017)

The US health care system faces an unsustainable trajectory of high costs and inconsistent outcomes. The fee-for-service payment model has contributed to inefficiency, and new payment methods are a promising approach to improving value. Health reforms are needed to increase patient access, reduce costs, and improve health care quality, and the landmark Medicare Access and CHIP Reauthorization Act presents a roadmap for reform. The product of a collaboration between primary care and cardiology clinicians, this review describes a conceptual approach to delivery and payment reforms that aim to better support primary care-cardiology comanagement of chronic cardiovascular disease (CVD).Few existing alternative payment models specifically address long-term management of CVD. Primary care medical homes and accountable care organizations come closest, but both emphasize primary care, and cardiologists have often not been well engaged. A collaborative care framework should articulate distinct roles and responsibilities for primary care and cardiology in CVD comanagement. Finally, a series of payment models aim to better support clinicians in providing accountable, seamless, and patient-centered cardiac care.Clinical leadership is essential during this time of change in the health care system. Patients often struggle to navigate a fragmented and expensive system, whereas clinicians often practice with incomplete information about tests, treatments, and recommendations by their colleagues. The payment models described in this review offer an opportunity to create more satisfying approaches to patient care while improving value. These models have potential to support more effective coordination and to facilitate broader health care system transformation.
Gastrointestinal Stromal Tumor of the Prostate
Authors: Yazan Z. Alabed
Journal: Clinical Nuclear Medicine (2017)

Abstract A 49-year-old man presented for routine general physical examination was found with an enlarged prostate gland without associated symptoms. Ultrasound followed by computed tomography (CT) of abdomen and pelvis confirmed a markedly enlarged heterogeneous prostate gland. Subsequently, a staging flourine-18 fluorodeoxyglucose ( 18 F-FDG) positron emission tomography (PET/CT) scan revealed intensely FDG-avid mass involving the prostate, which was biopsied as gastrointestinal stromal tumor (GIST). The patient was treated with imatinib and a follow-up PET/CT scan showed complete metabolic response. 18 F-FDG PET/CT scan is useful in staging and follow-up of this very rare extragastrointestinal stromal tumor (EGIST).
A comparison of Numeric Pain Rating Scale (NPRS) and the Visual Analog Scale (VAS) in patients with chronic cancer-associated pain.
Authors: Shagufta Firdous, Zankhana Mehta, Carlos Fernandez, Bertarnd Behm, Mellar Davis
Journal: Journal of Clinical Oncology (2017)

217 Background: Though numerical rating scales (NRS) are frequently used, a subset of patients do not understand the abstract nature on NRS and use quality descriptors of severity. We used a visual analog scale (VAS) using descriptors of “good day”, “average day” and “bad day” along a 10-cm line and compared it to a NRS in patients with cancer diagnosis and pain 1 month or longer. Methods: Eligible patients were verbally consented and completed the two scales. We asked patients thoughts about which they felt was the more appropriate scale to gauge their pain. The scales were compared by the distance from the extreme left of the line to the mark the patient placed on the VAS. Additional data included demographic and diagnosis information. The VAS and NRS were compared using two-sample t-tests or Wilcoxon rank-sum tests and Pearson’s chi-square or Fisher’s exact tests, as appropriate. The relationship between the numeric pain scale and the visual analog scale is described using Pearson’s correlation coefficient. Results: Full data was provided from 94 patient surveys who completed surveys. The mean age was 61 years old, 56.4% were female, and 78.0% had metastatic cancer. Numerous cancer types were reported with gastrointestinal and lung cancers being the most common (30.1% and 23.7%, respectively). The mean NRS rating reported by patients was 5.9 and for the VAS 4.9. Sixty patients (63.8%) preferred the NRS, 32 (34.0%) preferred the VAS, and 2 (2.1%) reported no preference. Patients who preferred the NRS reported a higher NRS rating than patients who preferred the VAS (mean NRS of 6.3 compared to 5.2, p = 0.0409). VAS ratings were higher among patients who preferred the NRS but the difference was not statistically significant (mean rating of 5.2 vs. 4.4, p = 0.1894). There were no differences in patient characteristics between the two groups. There was a moderate association between patients’ NRS and VAS ratings. The Pearson correlation coefficient was 0.653 (p &lt; 0.0001). Conclusions: Majority of patients of all ages and both genders prefer NRS. Future studies involving larger number of patients and adding a question about the reason of scale preference may provide better understanding for scale preference.
Engagement of MHC class I by the inhibitory receptor LILRB1 suppresses macrophages and is a target of cancer immunotherapy
Authors: Amira A. Barkal, Kipp Weiskopf, Kevin S. Kao, Sydney R. Gordon, Benyamin Rosental, Ying Y. Yiu, Benson M. George, Maxim Markovic, Nan G. Ring, Jonathan M. Tsai, Kelly M. McKenna, Po Yi Ho, Robin Z. Cheng, James Y. Chen, Layla J. Barkal, Aaron M. Ring, Irving L. Weissman, Roy L. Maute
Journal: Nature Immunology (2017)
Abstract 15571: Pathological Stress Response in Adult Hearts after Disturbed Prenatal Development
Authors: Jette Strasen, Patrick Langner, Manuela Magarin, Arnd Heuser, Timothy C Cox, Ludwig Thierfelder, Jorg-Detlef Drenckhahn
Journal: Circulation (2010)

The embryonic mouse heart has recently been shown to have a remarkable regenerative capacity in response to tissue mosaicism for mitochondrial dysfunction. Despite the functional loss of 50% of myo...
Enhancing proteasome-inhibitory activity and specificity of bortezomib by CD38 targeted nanoparticles in multiple myeloma
Authors: Pilar de la Puente, Micah J. Luderer, Cinzia Federico, Abbey Jin, Rebecca C. Gilson, Christopher Egbulefu, Kinan Alhallak, Shruti Shah, Barbara Muz, Jennifer Sun, Justin King, Daniel Kohnen, Noha Nabil Salama, Samuel Achilefu, Ravi Vij, Abdel Kareem Azab
Journal: Journal of Controlled Release (2017)
Dacomitinib, a pan-ErbB inhibitor, inhibits proliferation and invasion of pancreatic ductal adenocarcinoma cells
Authors: F. Esmaeili, M. Momeny, H. Yousefi, H. Eyvani, Z. Sabourinejad, F. Barghi, S. Vaezijoze, Z. Alishahi, G. Zarrinrad, A. Poursheikhani, E. Aboutorabi, G. Sankanian, F. Moghaddaskho, S. Shamsaiegahkani, J. Tavakkoly-Bazzaz, K. Alimoghaddam, A. Ghavamzadeh, S. Ghaffari
Journal: Annals of Oncology (2017)
Emotional granularity and the musical enjoyment of sadness itself
Authors: Nathaniel F Barrett, Jay Schulkin, Javier Bernacer
Journal: Behavioral and Brain Sciences (2017)

Abstract We contest the claim that musically induced sadness cannot be enjoyable in itself. This possibility is supported by closer attention to a musical experience as well as cases of affective reversal, such as the “hedonic flip” of painful feelings. We propose that the affective reversal of sadness in music is due to the high granularity of musically induced emotion.
Gene mutational profiling of Chinese EGFR-T790M mutation NSCLC patients required resistance to osimertinib by next generation sequencing
Authors: C. Xu, W. Wang, W. Zhuang, Z. Song, G. Lin, X. Chen, Y. Zhu, M. Fang, H. Zhang, H. Wang, J. Zhang, Z. Yu, R. Chen, Y. Guan, X. Yi, Y. Chen, G. Chen, T. Lv, Y. Song
Journal: Annals of Oncology (2017)
Atypical G Protein β5 Promotes Cardiac Oxidative Stress, Apoptosis, and Fibrotic Remodeling in Response to Multiple Cancer Chemotherapeutics
Authors: Sreemoyee Chakraborti, Arnab Pramanick, Sudipta Saha, Somnath Singha Roy, Arnab Ray Chaudhuri, Madhusudan Das, Sujoy Ghosh, Adele Stewart, Biswanath Maity
Journal: Cancer Research (2017)

The clinical use of multiple classes of cancer chemotherapeutics is limited by irreversible, dose-dependent, and sometimes life-threatening cardiotoxicity. Though distinct in their mechanisms of action, doxorubicin, paclitaxel, and 5-FU all induce rapid and robust upregulation of atypical G protein Gβ5 in the myocardium correlating with oxidative stress, myocyte apoptosis, and the accumulation of proinflammatory and profibrotic cytokines. In ventricular cardiac myocytes (VCM), Gβ5 deficiency provided substantial protection against the cytotoxic actions of chemotherapeutics, including reductions in oxidative stress and simultaneous attenuation of ROS-dependent activation of the ATM and CaMKII proapoptotic signaling cascades. In addition, Gβ5 loss allowed for maintenance of Δψm, basal mitochondrial calcium uniporter expression, and mitochondrial Ca2+ levels, effects likely to preserve functional myocyte excitation-contraction coupling. The deleterious effects of Gβ5 are not restricted to VCM, however, as Gβ5 knockdown also reduces chemotherapy-induced release of proinflammatory cytokines (e.g., TNFα), hypertrophic factors (e.g., ANP), and profibrotic factors (e.g., TGFβ1) from both VCM and ventricular cardiac fibroblasts, with the most dramatic reduction occurring in cocultured cells. Our experiments suggest that Gβ5 facilitates the myofibroblast transition, the persistence of which contributes to pathologic remodeling and heart failure. The convergence of Gβ5-mediated, ROS-dependent signaling pathways in both cell types represents a critical etiological factor in the pathogenesis of chemotherapy-induced cardiotoxicity. Indeed, intracardiac injection of Gβ5-targeted shRNA allowed for heart-specific protection against the damaging impact of chronic chemotherapy. Together, our results suggest that inhibition of Gβ5 might represent a novel means to circumvent cardiotoxicity in cancer patients whose treatment regimens include anthracyclines, taxanes, or fluoropyrimidines.Significance: These findings suggest that inhibiting an atypical G-protein might provide a strategy to limit the cardiotoxicity in cancer patients treated with anthracyclines, taxanes, or fluoropyrimidines. Cancer Res; 78(2); 528-41. ©2017 AACR.
Multiple Innovations in Genetic and Epigenetic Mechanisms Cooperate to Underpin Human Brain Evolution
Authors: Mainá Bitar, Guy Barry
Journal: Molecular Biology and Evolution (2017)

Our knowledge of how the human brain differs from those of other species in terms of evolutionary adaptations and functionality is limited. Comparative genomics reveal valuable insight, especially the expansion of human-specific noncoding regulatory and repeat-containing regions. Recent studies add to our knowledge of evolving brain function by investigating cellular mechanisms such as protein emergence, extensive sequence editing, retrotransposon activity, dynamic epigenetic modifications, and multiple noncoding RNA functions. These findings present an opportunity to combine newly discovered genetic and epigenetic mechanisms with more established concepts into a more comprehensive picture to better understand the uniquely evolved human brain.
Michael Gerald FitzGerald
Authors: Alex Wright, Robert FitzGerald
Journal: BMJ (2017)

Widely known as “Fitz,” Michael Gerald FitzGerald was a respected and well liked consultant physician specialising in clinical diabetes and thyroid disease at the General Hospital Birmingham, where he led the department from 1964 to his retirement in 1989. A fine physician, a man of great integrity and a delightful personality, he was popular with patients, their families, and the staff who worked with him at the hospital where he both started and finished his medical career.

Born in Birmingham on 25 August 1924, the only child of Winifred and Major Lancelot FitzGerald, Michael was schooled during the war years. Perhaps a slow starter, he nonetheless achieved a scholarship for King Edward’s School, he took his school certificates during the Birmingham blitz. He was an active sportsman, representing the school in cricket, hockey, and rugby, and he ended up achieving good results in his highers, a scholarship in biology, and a scholarship entrance into Birmingham University Medical School.

His medical school years (1942-47) gave him many happy memories. He studied exceptionally hard, but he also became an integral part of the hospitals social life. He won the Bertram Windle anatomy prize 1944, the Samson Gamgee …