tbuckley/cabot-search huggingface dataset:
Abstract 17619: Interstage Growth Trajectory is Associated With Interstage Survival in the Absence of Post-operative Complications Following the Norwood Procedure
Authors: Charles F Evans, Danielle S Abraham, Sunjay Kaushal, Geoffrey L Rosenthal
Journal: Circulation (2015)

Introduction: Low birth and procedure weight have been identified as risk factors for mortality after the Norwood operation. There are no strong data to show that growth during the interstage period is associated with interstage survival. Hypothesis: We hypothesize that positive growth trajectory following the Norwood operation is associated with improved interstage transplant-free survival. Methods: We conducted a retrospective cohort study using the National Pediatric Cardiology Quality Improvement Database. The exposure, growth trajectory, was the slope of the least-squares regression line of body mass index-for-age Z-scores over time. The outcome was interstage transplant-free survival. We constructed a multivariable logistic regression model to examine the association between interstage growth trajectory and interstage transplant-free survival. Results: The study population included 1501 infants who were discharged alive from the Norwood operation between June 2008 and January 2015. The most common diagnosis was hypoplastic left heart syndrome with aortic and mitral atresia (34%). The most common operation was the Norwood procedure with a right ventricle to pulmonary artery shunt (55%). Interstage survival was 89%. Growth trajectory was positive in 945/1392 (68%) for whom sufficient data were available. The occurrence of at least one post-operative complication was identified as an effect measure modifier (p=0.02). When adjusted for sex, birth weight, presence of a secondary cardiac diagnosis, type of operation and post-operative arrhythmia, positive growth trajectory was significantly associated with interstage survival in the absence (OR=3.7, 95% CI 1.7, 8.0) but not in the presence (OR=1.1, 95% CI 0.7, 1.7) of post-operative complications. Conclusions: Positive interstage growth trajectory is significantly associated with transplant-free interstage survival in the absence of post-operative complications.
A grounded theory analysis of oncology nurses' perceptions of early palliative care in the context of ambulatory care.
Authors: Shan Darrel Mohammed, Pamela Savage, Camilla Zimmermann
Journal: Journal of Clinical Oncology (2017)

96 Background: In early palliative care (EPC), palliative supports and resources are provided at an earlier stage in the treatment trajectory. As major care providers, nurses play a pivotal role in ensuring the success of EPC as an emerging model of care delivery. In this study, we examine nurses’ perceptions of EPC in the context of ambulatory oncology care and explore how EPC fits within the broader professional mandate of nursing. Methods: We recruited nurses from several ambulatory care oncology clinics in a tertiary cancer hospital in Ontario, Canada. Nurses participated in semi-structured interviews seeking to qualitatively examine their attitudes and perceptions about EPC. Constructivist grounded theory guided our methods and analysis. Results: A total of 20 nurses that included six staff nurses, ten nurse practitioners, and four advanced practice nurses completed interviews. Participants worked in a variety of clinic settings such as breast, pancreatic, head and neck, and hematology. The core category Perceiving EPC as Synonymous with Fundamental Nursing Care encompasses three subcategories: (1) Prioritizing immediate care needs – recognizing the need for EPC to manage immediate pain and symptom management concerns; (2) Care coordination – viewing EPC as linking resources and organizing interprofessional care; and (3) Safeguarding and preventative care – initiating EPC to protect against difficult transitions between phases of treatment and to prevent being unprepared for active dying. Conclusions: This was the first study to qualitatively examine nurses’ perception of EPC. Nurses not only recognize the value of EPC to ensure good quality care for patients with cancer and their families, but also perceive this care as deeply embedded within the core values of nursing. Recognizing how nurses view EPC has implications for expanding the professional scope of nursing in palliative care and for preparing nurses for the complexities of this work.
H3K27me3 dynamics dictate evolving uterine states in pregnancy and parturition
Authors: Patrice Nancy, Johan Siewiera, Gabrielle Rizzuto, Elisa Tagliani, Ivan Osokine, Priyanka Manandhar, Igor Dolgalev, Caterina Clementi, Aristotelis Tsirigos, Adrian Erlebacher
Journal: Journal of Clinical Investigation (2017)

Uncovering the causes of pregnancy complications such as preterm labor requires greater insight into how the uterus remains in a noncontractile state until term and then surmounts this state to enter labor. Here, we show that dynamic generation and erasure of the repressive histone modification tri-methyl histone H3 lysine 27 (H3K27me3) in decidual stromal cells dictate both elements of pregnancy success in mice. In early gestation, H3K27me3-induced transcriptional silencing of select gene targets ensured uterine quiescence by preventing the decidua from expressing parturition-inducing hormone receptors, manifesting type 1 immunity, and most unexpectedly, generating myofibroblasts and associated wound-healing responses. In late gestation, genome-wide H3K27 demethylation allowed for target gene upregulation, decidual activation, and labor entry. Pharmacological inhibition of H3K27 demethylation in late gestation not only prevented term parturition, but also inhibited delivery while maintaining pup viability in a noninflammatory model of preterm parturition. Immunofluorescence analysis of human specimens suggested that similar regulatory events might occur in the human decidua. Together, these results reveal the centrality of regulated gene silencing in the uterine adaptation to pregnancy and suggest new areas in the study and treatment of pregnancy disorders.
The paradox of tragedy and emotional response to simulation
Authors: Patrick Colm Hogan
Journal: Behavioral and Brain Sciences (2017)

Abstract The insightful analysis of Menninghaus et al. could be deepened and rendered more systematic by recognizing that our emotional enjoyment of tragedy – and our response to fiction more generally – are versions of what happens with simulation. They derive from the operation and evolutionary function of simulation. Once we understand emotion in simulation, we largely understand emotion in tragedy (and fiction).
Procedimentos de investigação em epidemias internacionais de toxinfecções alimentares pela Enter-net
Authors: J C Desenclos, I. S.T. Fisher, O N Gill
Journal: Eurosurveillance (1999)

A livre circulacao de pessoas, bens e alimentos, no seio dos paises da Uniao Europeia (UE), fez aumentar a oportunidade para a ocorrencia de surtos internacionais de toxinfeccoes alimentares, apesar dos esforcos para reduzir a contaminacao microbiologica dos produtos alimentares. A implementacao da rede internacional de vigilância Enter-net (anterior Salm-net) deve tornar possivel a identificacao precoce e a investigacao destes surtos internacionais (1).
Early drop of LV ejection fraction can predict trastuzumab-related cardiotoxicity in patients with breast cancer
Authors: J. Cho, E.K. Kim, K.H. Yoo, H. Lee, H.K. Kim, M.H. Heo, J. Park, J.S. Ahn, Y-H Im, Y.H. Park
Journal: Annals of Oncology (2017)
What is art and how does it differ from aesthetics?
Authors: Robert Kreuzbauer
Journal: Behavioral and Brain Sciences (2017)

Abstract Art objects differ from other objects because they are intentionally created to embody a producer's (i.e., artist's) expression. Hence, art objects are social objects whose appeal and value are determined largely by the strategic interaction between the artist and the audience. I discuss several aspects of how strategic interaction can affect an art object's perceived value and aesthetic appeal.
P3.01-024 Drastic Morphological and Molecular Differences between Lymph Node Micrometastatic Tumors and Macrometastatic Tumors of Lung Adenocarcinoma
Authors: Nao Aramaki, Genichiro Ishii, Keiju Aokage, Tomoyuki Hishida, Junji Yoshida, Masahiro Tsuboi, Naohiro Kajiwara, Tatsuo Ohira, Norihiko Ikeda
Journal: Journal of Thoracic Oncology (2017)
Left or right? Directions to stem cell engraftment
Authors: Mirjam E. Belderbos, Leonid Bystrykh, Gerald de Haan
Journal: The Journal of Experimental Medicine (2017)

In this issue of JEM, Wu et al. (https://doi.org/10.1084/jem.20171341) use genetic barcoding of macaque hematopoietic stem cells to demonstrate that, after transplantation, HSCs are very asymmetrically distributed and uncover a thymus-independent pathway for mature T cell production in the bone marrow.
Abstract 12229: Myocardial Ischemia During Mental Stress: Role of Coronary Artery Disease Burden and Vasomotion
Authors: Ronnie Ramadan, David Sheps, A. Maziar Zafari, Fabio Esteves, Douglas Bremner, Viola Vaccarino, Arshed Quyyumi
Journal: Circulation (2013)

Background:  Myocardial ischemia induced by mental stress (MSI) portends a worse prognosis in patients with CAD, irrespective of traditional risk factors or physical stress ischemia (PSI). Yet, the mechanisms underlying MSI and whether they differ from those underlying PSI remain unclear.   Hypothesis:  Compared to PSI that is largely secondary to epicardial atherosclerotic burden, MSI is primarily due to vasomotor changes.   Methods:  Patients (n=384) with angiographically documented CAD underwent 99m-Tc-sestamibi myocardial perfusion imaging at rest and following both mental and physical stress testing, performed on separate days. The angiographic severity and extent of CAD were quantified using the Gensini and Sullivan coronary scoring systems. Peripheral arterial tonometry (PAT) was used to assess the digital microvascular tone during mental stress as a ratio of pulse wave amplitude during speech compared to baseline with a ratio≤1 signifying a vasoconstrictor response.   Results:  MSI occurred in 52 (14%) patients and PSI in 125 (33%). All hemodynamic measures increased in response to mental stress (P≤0.001), and the increase was similar in those with or without MSI. CAD severity and extent scores were similar in those with and without MSI (P>0.7 for all), whereas they were greater in those with compared to those without PSI (p≤0.001 for all). Notably, in those with PSI, the occurrence of MSI was not associated with more severe CAD (Figure). The PAT ratio was lower in those with compared to those without MSI (0.6±0.4 vs. 0.8±0.5, P=0.009). In a multivariate analysis, a lower PAT ratio during mental stress was the only independent predictor of MSI (P=0.009), whereas angiographic severity and extent of CAD independently predicted PSI.   Conclusions:  The degree of digital microvascular constriction, and not the angiographic burden of CAD, is associated with MSI. Varying etiologies of MSI compared to PSI may require different therapeutic interventions that require further study.
Public spending cuts are linked to 120 000 excess deaths in England, study suggests
Authors: Abi Rimmer
Journal: BMJ (2017)

Cuts to public spending on healthcare and social care are linked to around 120 000 excess deaths from 2010 to 2017, researchers have found. In a paper published in BMJ Open , they said that spending constraints had produce a substantial mortality gap in England.1

The study found that deaths in England fell by an average of 0.77% a year from 2001 to 2010 but then rose by an average of 0.87% a year from 2011 to 2014.

From 2010 to 2014 the NHS in England had a real terms annual increase in government funding of …
Inflammatory Cytokines Stabilize SOXC Transcription Factors to Mediate the Transformation of Fibroblast-Like Synoviocytes in Arthritic Disease
Authors: Pallavi Bhattaram, George Muschler, Viktor Wixler, Véronique Lefebvre
Journal: Arthritis & Rheumatology (2017)

Objective Fibroblast‐like synoviocytes (FLS) produce key synovial fluid and tissue components to ensure joint integrity under healthy conditions, whereas they become cancer‐like and aggressively contribute to joint degeneration in inflammatory arthritis. The aim of this study was to determine whether the SOXC transcription factors SOX4 and SOX11, whose functions are critical in joint development and many cancer types, contribute to FLS activities under normal and inflammatory conditions. Methods We inactivated the SOXC genes in FLS from adult mice and studied the effect on joint homeostasis and tumor necrosis factor (TNF)–induced arthritis. We used primary cells and synovial biopsy specimens from arthritis patients to analyze the interactions between inflammatory signals and SOXC proteins. Results Postnatal inactivation of the SOXC genes had no major effect on joint integrity in otherwise healthy mice. However, it hampered synovial hyperplasia and joint degeneration in transgenic mice expressing human TNF. These effects were explained by the ability of SOX4/11 to amplify the pathogenic impact of TNF on FLS by increasing their survival and migration. SOXC RNA levels were not changed by TNF and other proinflammatory cytokines, but SOXC proteins were strongly stabilized and able to potentiate the TNF‐induced up‐regulation of genes involved in FLS transformation. Substantiating the relevance of these findings in human disease, SOXC protein levels, but not RNA levels, were significantly higher in inflamed synovium than in noninflamed synovium from arthritis patients. Conclusion SOXC proteins are targets and pivotal mediators of proinflammatory cytokines during FLS transformation in arthritic diseases. Targeting of these proteins could thus improve current strategies to treat arthritic diseases and possibly other inflammatory diseases.
The behavioral constellation of deprivation may be best understood as risk management
Authors: Dorsa Amir, Matthew R. Jordan
Journal: Behavioral and Brain Sciences (2017)

Abstract Although the authors make a compelling case that early-life deprivation leads to present orientation, we believe that such behaviors may be better understood in terms of an underlying risk-management strategy, in which those who experience such deprivation are more risk-averse. The model we sketch accommodates the authors' present-orientation observations and further explains differences in risk preferences and social preferences.
Phase Ib study of ribociclib (RIB) + letrozole (LET) in a subset of Asian patients (pts) with hormone receptor-positive (HR+), human epidermal growth factor receptor 2-negative (HER2–) advanced breast cancer (ABC)
Authors: Y-S Yap, Y. Ito, O. Bornstein, Y. Han, T. Samant, X. Liu, J. Chiu
Journal: Annals of Oncology (2017)
Abstract 17999: Synthetic HGF-Mimetic Induces Endothelial Phenotype in Wharton’s Jelly Mesenchymal Stem Cells and Promotes Angiogenesis
Authors: Zubair Shah, Tanner Buehler, Lei Chen, Robert Vincent, Brandon Blount, Alex Burnett, Jeryl Hauptman, Magdy Girgis, Bhaskar Das, Buddhadeb Dawn
Journal: Circulation (2016)

Introduction: Although hepatocyte growth factor (HGF) has been shown to increase capillary density, short half-life remains a major limiting factor for therapeutic use. The potential utility of umb...
P2.07-017 Association between Thyroid Dysfunction and Progression-Free Survival in Patients with Non-Small Cell Lung Cancer Received Nivolumab
Authors: T. Funazo, H. Ozasa, T. Nomizo, Y. Yasuda, T. Tsuji, H. Yoshida, Y. Sakamori, H. Nagai, T. Hirai, Y. Kim
Journal: Journal of Thoracic Oncology (2017)
Rheumatic disorders associated with immune checkpoint inhibitors in patients with cancer—clinical aspects and relationship with tumour response: a single-centre prospective cohort study
Authors: Marie Kostine, Léa Rouxel, Thomas Barnetche, Rémi Veillon, Florent Martin, Caroline Dutriaux, Léa Dousset, Anne Pham-Ledard, Sorilla Prey, Marie Beylot-Barry, Amaury Daste, Marine Gross-Goupil, Julie Lallier, Alain Ravaud, Edouard Forcade, Bernard Bannwarth, Marie-Elise Truchetet, Christophe Richez, Nadia Mehsen, Thierry Schaeverbeke
Journal: Annals of the Rheumatic Diseases (2017)

Objectives To evaluate the prevalence and type of rheumatic immune-related adverse events (irAEs) in patients receiving immune checkpoint inhibitors (ICIs), as well as the correlation with tumour response. Methods This was a single-centre prospective observational study including all cancer patients receiving ICIs. The occurrence of irAEs and tumour response was assessed on a regular basis. Patients who experienced musculoskeletal symptoms were referred to the department of rheumatology for clinical evaluation and management. Results From September 2015 to May 2017, 524 patients received ICIs and 35 were referred to the department of rheumatology (6.6%). All but one of the rheumatic irAEs occurred with anti-programmed cell death protein 1(PD-1)/PD-1 ligand 1(PD-L1) antibodies, with a median exposure time of 70 days. There were two distinct clinical presentations: (1) inflammatory arthritis (3.8%) mimicking either rheumatoid arthritis (n=7), polymyalgia rheumatica (n=11) or psoriatic arthritis (n=2) and (2) non-inflammatory musculoskeletal conditions (2.8%; n=15). One patient with rheumatoid arthritis was anti-cyclic citrullinated peptide (anti-CCP) positive. Nineteen patients required glucocorticoids, and methotrexate was started in two patients. Non-inflammatory disorders were managed with non-steroidal anti-inflammatory drugs, analgesics and/or physiotherapy. ICI treatment was pursued in all but one patient. Patients with rheumatic irAEs had a higher tumour response rate compared with patients without irAEs (85.7% vs 35.3%; P&lt;0.0001). Conclusion Since ICIs are used with increasing frequency, knowledge of rheumatic irAEs and their management is of major interest. All patients were responsive either to low-to-moderate doses of prednisone or symptomatic therapies and did not require ICI discontinuation. Furthermore, tumour response was significantly higher in patients who experienced rheumatic irAEs.
Interferon-γ Signaling in Melanocytes and Melanoma Cells Regulates Expression of CTLA-4
Authors: Xuan Mo, Hanghang Zhang, Sarah Preston, Kayla Martin, Bo Zhou, Nish Vadalia, Ana M. Gamero, Jonathan Soboloff, Italo Tempera, M. Raza Zaidi
Journal: Cancer Research (2017)

Abstract CTLA4 is a cell surface receptor on T cells that functions as an immune checkpoint molecule to enforce tolerance to cognate antigens. Anti–CTLA4 immunotherapy is highly effective at reactivating T-cell responses against melanoma, which is postulated to be due to targeting CTLA4 on T cells. Here, we report that CTLA4 is also highly expressed by most human melanoma cell lines, as well as in normal human melanocytes. Interferon-γ (IFNG) signaling activated the expression of the human CTLA4 gene in a melanocyte and melanoma cell–specific manner. Mechanistically, IFNG activated CTLA4 expression through JAK1/2-dependent phosphorylation of STAT1, which bound a specific gamma-activated sequence site on the CTLA4 promoter, thereby licensing CBP/p300-mediated histone acetylation and local chromatin opening. In melanoma cell lines, elevated baseline expression relied upon constitutive activation of the MAPK pathway. Notably, RNA-seq analyses of melanoma specimens obtained from patients who had received anti–CTLA4 immunotherapy (ipilimumab) showed upregulation of an IFNG-response gene expression signature, including CTLA4 itself, which correlated significantly with durable response. Taken together, our results raise the possibility that CTLA4 targeting on melanoma cells may contribute to the clinical immunobiology of anti–CTLA4 responses. Significance: These findings show that human melanoma cells express high levels of the immune checkpoint molecule CTLA4, with important possible implications for understanding how anti-CTLA4 immunotherapy mediates its therapeutic effects. Cancer Res; 78(2); 436–50. ©2017 AACR.
Updated findings of a first-in-human, phase I study of margetuximab (M), an Fc-optimized chimeric monoclonal antibody (MAb), in patients (pts) with HER2-positive advanced solid tumors.
Authors: Howard A. Burris, Giuseppe Giaccone, Seock-Ah Im, Todd Michael Bauer, Do-Youn Oh, Suzanne Fields Jones, Jeffrey L. Nordstrom, Hua Li, David A Carlin, Jan E. Baughman, Robert Joseph Lechleider, Yung-Jue Bang
Journal: Journal of Clinical Oncology (2015)

523 Background: Fc-dependent mechanisms such as antibody-dependent cellular cytotoxicity (ADCC) may be important for the activity of MAbs. M is a MAb to HER2 engineered for increased Fc-domain binding affinity to both low affinity variants of the activating Fcγ receptor, CD16A. In preclinical studies, M showed enhanced ADCC compared to an unmodified precursor. Results from the initial dose escalation have previously been reported. Here we describe pharmacokinetics (PK), safety and activity data for the expansion cohort and an alternative schedule, including responses in patients with refractory breast cancer (BC). Methods: Pts with refractory carcinomas that overexpress HER2 for whom no standard therapy was available were enrolled. Pt cohorts received escalating doses of M weekly for 3 of every 4 weeks (Regimen A) or every 3 weeks (Regimen B) by intravenous infusion in a 3+3 (Regimen A) or 6+6 (Regimen B) design. Additional safety and activity data were obtained in expansion cohorts of each regimen. Tumor response was determined using RECISTv1.1. PK was evaluated during all cycles. Results: Fifty-two patients received M (34 patients received 0.1 to 6.0 mg/kg in Regimen A and 18 patients received 10 to 18 mg/kg in Regimen B). The maximum tolerated dose was not exceeded for either regimen. Treatment was well-tolerated, with mostly Grade 1 and 2 toxicities consisting of infusion-related reactions and constitutional symptoms such as pyrexia, nausea, anemia, diarrhea, and fatigue. Partial responses were observed in 8 patients and stable disease in 21 patients. Tumor reductions were observed in 11 of 19 patients with BC, including 4 patients with confirmed partial responses, 3 of whom had received prior trastuzumab and lapatinib, with several durable responses of > 30 weeks. Median progression free survival for patients with BC was 169 days. PK analysis showed that doses of 3 mg/kg in Regimen A and all doses in Regimen B achieved steady state trough levels sufficient to inhibit HER2 signaling. Conclusions: The results indicate that M is tolerated well and has promising activity in HER2-positive tumors including BC. Further development is ongoing. Clinical trial information: NCT01148849.