tbuckley/cabot-search huggingface dataset:
Circulation of Carcinogenic Polycyclic Aromatic Hydrocarbons in the Human Environment and Cancer Prevention
Authors: Shabad Lm
Journal: JNCI Journal of the National Cancer Institute (1980)

This editorial discusses the distribution of carcinogens in the human environment and stresses the idea that both the accumulation processes and the breakdown of carcinogens can coexist in humans. Therefore, prevention of tumors depends on comprehensive studies of the carcinogenic action of some chemicals and on information not only on the transmission of these compounds in the human environment but also on their metabolism within the body.
Use of systemic corticosteroids for atopic dermatitis: International Eczema Council consensus statement
Authors: A.M. Drucker, K. Eyerich, M.S. de Bruin-Weller, J.P. Thyssen, P.I. Spuls, A.D. Irvine, G. Girolomoni, S. Dhar, C. Flohr, D.F. Murrell, A.S. Paller, E. Guttman-Yassky
Journal: British Journal of Dermatology (2017)

Guidelines discourage the use of systemic corticosteroids for atopic dermatitis (AD), but their use remains widespread. To reach consensus among an international group of AD experts on the use of systemic corticosteroids for AD. A survey consisting of statements accompanied by visual analogue scales ranging from 'strongly disagree' to 'neutral' to 'strongly agree' was distributed to the International Eczema Council (IEC). Consensus was reached in agreement on a statement if < 30% of respondents marked to the left of 'neutral' towards 'strongly disagree'. Sixty of 77 (78%) IEC members participated. Consensus was reached on 12 statements, including that systemic corticosteroids should generally be avoided but can be used rarely for severe AD under certain circumstances, including a lack of other treatment options, as a bridge to other systemic therapies or phototherapy, during acute flares in need of immediate relief, in anticipation of a major life event or in the most severe cases. If used, treatment should be limited to the short term. Most respondents agreed that systemic corticosteroids should never be used in children, but consensus was not reached on that statement. The conclusions of our expert group are limited by a dearth of high‐quality published evidence. If more stringent consensus criteria were applied (e.g. requiring < 20% of respondents marking towards 'strongly disagree'), consensus would have been reached on fewer statements. Based on expert opinion from the IEC, routine use of systemic corticosteroids for AD is generally discouraged and should be reserved for special circumstances.
血管周囲細胞外マトリックスヒドロゲルは天然マトリックス微細構造を模倣し,塩基性線維芽細胞増殖因子を介して血管新生を促進する【Powered by NICT】
Authors: R Fercana George, Yerneni Saigopalakrishna, Billaud Marie, C Hill Jennifer, VanRyzin Paul, D Richards Tara, M Sicari Brian, A Johnson Scott, F Badylak Stephen, G Campbell Phil, G Gleason Thomas, A Phillippi Julie
Journal: Biomaterials (2017)
Understanding the functions and relationships of the glymphatic system and meningeal lymphatics
Authors: Antoine Louveau, Benjamin A. Plog, Salli Antila, Kari Alitalo, Maiken Nedergaard, Jonathan Kipnis
Journal: Journal of Clinical Investigation (2017)

Recent discoveries of the glymphatic system and of meningeal lymphatic vessels have generated a lot of excitement, along with some degree of skepticism. Here, we summarize the state of the field and point out the gaps of knowledge that should be filled through further research. We discuss the glymphatic system as a system that allows CNS perfusion by the cerebrospinal fluid (CSF) and interstitial fluid (ISF). We also describe the recently characterized meningeal lymphatic vessels and their role in drainage of the brain ISF, CSF, CNS-derived molecules, and immune cells from the CNS and meninges to the peripheral (CNS-draining) lymph nodes. We speculate on the relationship between the two systems and their malfunction that may underlie some neurological diseases. Although much remains to be investigated, these new discoveries have changed our understanding of mechanisms underlying CNS immune privilege and CNS drainage. Future studies should explore the communications between the glymphatic system and meningeal lymphatics in CNS disorders and develop new therapeutic modalities targeting these systems.
THU0134 Interstitial lung disease and rheumatoid arthritis. multicenter study with tocilizumab
Authors: C Fernández-Díaz, J Narvaez-García, M Martín-Lόpez, P Rubio-Muñoz, S Castañeda-Sanz, N Vegas-Revenga, L Dominguez-Casas, V Calvo-Rio, M Gonzalez-Gay, R Blanco
Journal: Annals of the Rheumatic Diseases (2017)

<h3>Background</h3> Interstitial Lung Disease (ILD) is a severe extraarticular manifestation of rheumatoid arthritis (RA). AntiTNFα drugs and conventional disease-modifying anti-rheumatic drugs (DMARDs) such as methotrexate (MTX) have been involved in the development of ILD. IL6 has been implicated in the pathogenesis of ILD (Kobayashi J et al). However, a fatal case of exacerbation of ILD has been described with tocilizumab (TCZ) (Kawashiri SY el at). <h3>Objectives</h3> Our aim was to assess the efficacy and safety of TCZ in ILD associated with AR. <h3>Methods</h3> Multicenter study of RA patients with ILD treated with TCZ. ILD was diagnosed by high-resolution computed tomography (HRCT). TCZ was used at standard dose (8 mg/k/iv/4 weeks). We have analyzed the following variables: a) 1-point change in the degree of dyspnea according to the Modified Medical Research Council (MMRC); b) Forced Vital Capacity (FVC) improvement ≥10%; and improvement ≥10% in DLCO; c) HRCT, and d) joint assessment (DAS28 score). <h3>Results</h3> We studied 12 patients (9 women/3 men) with ILD related to RA. The mean age±SD was 57.1±16.1 years. The mean evolution of RA was 9±5.8 years. The patients had previously received the following DMARDs; MTX (n=12), leflunomide (LFN) (8) sulfasalazine (SSZ) (3) hydroxichloroquine (HCQ) (1) azathioprine (AZA) (2), gold salts (2). In addition, 11 patients had previously received biological drugs: adalimumab (4) anakinra: (1), etarnecept (4), rituximab (4), infliximab (1), certolizumab (1), abatacept (1). RA was seropositive in 11 cases (92%). Besides HRCT, the diagnosis of ILD was confirmed by biopsy in 4 patients. In 2 patients ILD was drug-related: MTX (n=2). TCZ was prescribed in monotherapy (n=8) or combined with other DMARDs (4). These DMARDs were: LFN (2), MTX (1), AZA (1). In many patients the dyspnea and DLCO remain stable (Table). After a follow-up of 12 months, 2 patients withdrew TCZ, 1 patient for ILD worsening and 1 patient for joint inefficacy. <h3>Conclusions</h3> In our knowledge, this is the largest series that assess the EPID associated with RA treated with TCZ. We observed that in many cases pulmonary involvement remains stable. <h3>References</h3> Kobayashi J et al. Chest 1995; 108: 311. Kawashiri SY el at. Rheumatol Int 2012; 32: 4023–6. <h3>Disclosure of Interest</h3> None declared
Light-switchable systems for remotely controlled drug delivery
Authors: Gayong Shim, Seungbeom Ko, Dongyoon Kim, Quoc-Viet Le, Gyu Thae Park, Jaiwoo Lee, Taekhyun Kwon, Han-Gon Choi, Young Bong Kim, Yu-Kyoung Oh
Journal: Journal of Controlled Release (2017)
Enhanced Acid Sphingomyelinase Activity Drives Immune Evasion and Tumor Growth in Non–Small Cell Lung Carcinoma
Authors: Katerina Kachler, Maximilian Bailer, Lisanne Heim, Fabian Schumacher, Martin Reichel, Corinna D. Holzinger, Sonja Trump, Susanne Mittler, Juliana Monti, Denis I. Trufa, Ralf J. Rieker, Arndt Hartmann, Horia Sirbu, Burkhard Kleuser, Johannes Kornhuber, Susetta Finotto
Journal: Cancer Research (2017)

The lipid hydrolase enzyme acid sphingomyelinase (ASM) is required for the conversion of the lipid cell membrane component sphingomyelin into ceramide. In cancer cells, ASM-mediated ceramide production is important for apoptosis, cell proliferation, and immune modulation, highlighting ASM as a potential multimodal therapeutic target. In this study, we demonstrate elevated ASM activity in the lung tumor environment and blood serum of patients with non-small cell lung cancer (NSCLC). RNAi-mediated attenuation of SMPD1 in human NSCLC cells rendered them resistant to serum starvation-induced apoptosis. In a murine model of lung adenocarcinoma, ASM deficiency reduced tumor development in a manner associated with significant enhancement of Th1-mediated and cytotoxic T-cell-mediated antitumor immunity. Our findings indicate that targeting ASM in NSCLC can act by tumor cell-intrinsic and -extrinsic mechanisms to suppress tumor cell growth, most notably by enabling an effective antitumor immune response by the host. Cancer Res; 77(21); 5963-76. ©2017 AACR.
Association Between Psychotic Experiences and Subsequent Suicidal Thoughts and Behaviors
Authors: Evelyn J. Bromet, Matthew K. Nock, Sukanta Saha, Carmen C. W. Lim, Sergio Aguilar-Gaxiola, Ali Al-Hamzawi, Jordi Alonso, Guilherme Borges, Ronny Bruffaerts, Louisa Degenhardt, Giovanni de Girolamo, Peter de Jonge, Silvia Florescu, Oye Gureje, Josep M. Haro, Yanling He, Chiyi Hu, Elie G. Karam, Viviane Kovess-Masfety, Sing Lee, Jean-Pierre Lepine, Zeina Mneimneh, Fernando Navarro-Mateu, Akin Ojagbemi, José Posada-Villa, Nancy A. Sampson, Kate M. Scott, Juan C. Stagnaro, Maria C. Viana, Miguel Xavier, Ronald C. Kessler, John J. McGrath
Journal: JAMA Psychiatry (2017)

Community-based studies have linked psychotic experiences (PEs) with increased risks of suicidal thoughts and behaviors (STBs). However, it is not known if these associations vary across the life course or if mental disorders contribute to these associations.To examine the temporal association between PEs and subsequent STBs across the life span as well as the influence of mental disorders (antecedent to the STBs) on these associations.A total of 33 370 adult respondents across 19 countries from the World Health Organization World Mental Health Surveys were assessed for PEs, STBs (ie, ideation, plans, and attempts), and 21 DSM-IV mental disorders. Discrete-time survival analysis was used to investigate the associations of PEs with subsequent onset of STBs.Prevalence and frequency of STBs with PEs, and odds ratios and 95% CIs.Of 33 370 included participants, among those with PEs (n = 2488), the lifetime prevalence (SE) of suicidal ideation, plans, and attempts was 28.5% (1.3), 10.8% (0.7), and 10.2% (0.7), respectively. Respondents with 1 or more PEs had 2-fold increased odds of subsequent STBs after adjusting for antecedent or intervening mental disorders (suicidal ideation: odds ratio, 2.2; 95% CI, 1.8-2.6; suicide plans: odds ratio, 2.1; 95% CI, 1.7-2.6; and suicide attempts: odds ratio, 1.9; 95% CI, 1.5-2.5). There were significant dose-response relationships of number of PE types with subsequent STBs that persisted after adjustment for mental disorders. Although PEs were significant predictors of subsequent STB onset across all life stages, associations were strongest in individuals 12 years and younger. After adjustment for antecedent mental disorders, the overall population attributable risk proportions for lifetime suicidal ideation, plans, and attempts associated with temporally prior PEs were 5.3%, 5.7%, and 4.8%, respectively.Psychotic experiences are associated with elevated odds of subsequent STBs across the life course that cannot be explained by antecedent mental disorders. These results highlight the importance of including information about PEs in screening instruments designed to predict STBs.
Automated brightfield multiplex immunohistochemistry to quantify biomarkers related to immune senescence: Relationships with survival in non-small cell lung cancer patients.
Authors: Paul Hofman, Mélanie Beaulande, Saima Ben Hadj, Gilles Erb, Jean-François Pomerol, Sandra Lassalle, Catherine Butori, Elodie Long, Kevin Washetine, Olivier Guerin, Joel Guigay, Jerome Mouroux, Sylvie Leroy, Charles Hugo Marquette, Veronique Hofman, Marius Ilie
Journal: Journal of Clinical Oncology (2017)

e20500 Background: Elderly patients have an eroded immune characterized by a progressive decline in immune surveillance that favors infection and cancer development. Tumor cells can escape immune surveillance by upregulating inhibitory immune checkpoint such as PD-L1. High expression of PD-L1 was reported in association with CD8 + T-cell exhaustion and increased levels of CD33 + myeloid-derived suppressor cells. Although low CD4/CD8 ratio is associated with increased mortality, the status of the CD4 + T-cells as a clinical marker of immunosenescence is less well characterized in the field of aging. The aim of this study was to determine the presence of immunosenescence biomarkers according to age in non-small cell lung cancer (NSCLC) patients and to evaluate them as predictive biomarkers of patients’ outcome. Methods: One hundred NSCLC patients, matched by age (50 patients &lt; 70 years, 50 patients ≥70 years) were included. An automated 4-Plex optical IHC assay was developed on the Discovery ULTRA automated stainer using monoclonal antibodies PD-L1 (SP263), CD4, CD8, and CD33. The stained slides were scanned with Nanozoomer HT 2.0 Scanner, and analyzed with Calopix software. Results: The CD4/CD8 ratio and PD-L1 expression in tumor and immune cells were significantly lower in elderly NSCLC patients ≥70 years than in age-paired patients, while absolute count of CD33 + was increased. Patients with CD4/CD8 ratio higher than two, high PD-L1 density and low CD33 + frequency achieved increase in median disease-free survival. Conclusions: Distribution of PD-L1, CD4, CD8, and CD33 cells was influenced by age in NSCLC patients. The proportion of CD8 + CD28- T cells, CD4+ T cells and CD4/CD8 ratio may be used as predictive biomarkers of anti-PD-L1 therapy efficacy in NSCLC patients. The automated 4-Plex IHC assay together with its respective digital analysis could serve as a tool for further characterizing tumors and their microenvironment and provide a better understanding of which patients may benefit from immunotherapy.
The Exaggerated Collagen Expression in Gvhd-Fibroblasts Is Effectively Inhibited By Therapeutic Concentration of Nilotinib
Authors: Elena Marinelli Busilacchi, Jacopo Olivieri, Nadia Viola, Antonella Poloni, Giorgia Mancini, Francesco Saraceni, Anna Campanati, Gaia Goteri, Silvia Svegliati, Armando Gabrielli, Attilio Olivieri
Journal: Blood (2016)
Polyglycerolated nanocarriers with increased ligand multivalency for enhanced in vivo therapeutic efficacy of paclitaxel
Authors: Trang Huyen Le Kim, Jeong Heon Yu, Hwiseok Jun, Moon Young Yang, Mi-Jin Yang, Jae-Woo Cho, Jin Woong Kim, Jee Seon Kim, Yoon Sung Nam
Journal: Biomaterials (2017)
A Spontaneous, Transplantable, Adrenal Cortical Tumor Arising in a Strain C Mouse&lt;xref ref-type="fn" rid="fn1"&gt;&lt;sup&gt;1&lt;/sup&gt;&lt;/xref&gt;
Authors: Dalton, Albert J., Edwards, Jesse E., Andervont, Howard B., Briggs, Virginia C.
Journal: JNCI Journal of the National Cancer Institute (1943)

Journal Article A Spontaneous, Transplantable, Adrenal Cortical Tumor Arising in a Strain C Mouse Get access Albert J. Dalton, Albert J. Dalton cytologist National Cancer Institute, National Institute of Health, United States Public Health Service Search for other works by this author on: Oxford Academic PubMed Google Scholar Jesse E. Edwards, Jesse E. Edwards formerly research fellow National Cancer Institute, National Institute of Health, United States Public Health Service Search for other works by this author on: Oxford Academic PubMed Google Scholar Howard B. Andervont, Howard B. Andervont principal biologist National Cancer Institute, National Institute of Health, United States Public Health Service Search for other works by this author on: Oxford Academic PubMed Google Scholar Virginia C. Briggs Virginia C. Briggs technical assistance National Cancer Institute, National Institute of Health, United States Public Health Service Search for other works by this author on: Oxford Academic PubMed Google Scholar JNCI: Journal of the National Cancer Institute, Volume 4, Issue 3, December 1943, Pages 329–338, https://doi.org/10.1093/jnci/4.3.329 Published: 01 December 1943
Abstract 13604: Physical and Affective Symptom Clusters Are Strongly Associated in Heart Failure
Authors: Quin E Denfeld, Jill M Gelow, Shirin O Hiatt, James O Mudd, Christopher V Chien, Christopher S Lee
Journal: Circulation (2015)

Introduction: The syndrome of heart failure (HF) is a constellation of both physical and affective symptoms. How physical and affective symptom clusters are associated, however, is not well understood. Hypothesis: There is a strong association between physical symptom clusters and affective symptom clusters among adults with moderate to advanced HF. Methods: This was a secondary analysis of combined data collected during two prospective cohort studies of symptoms among adults with moderate to advanced HF. Physical symptoms of dyspnea and wake disturbances were measured with the Heart Failure Somatic Perception Scale Dyspnea subscale (HFSPS-D) and the Epworth Sleepiness Scale (ESS), respectively. Affective symptoms of depression and anxiety were measured with the Patient Health Questionnaire-9 (PHQ-9) and the Brief Symptom Inventory Anxiety subscale (BSIANX), respectively. Physical and affective symptoms were clustered separately using latent mixture modeling and then compared using cross classification modeling and traditional comparative statistics (i.e. student’s t, Kendall’s tau-b and chi-square tests). Results: The average age of the sample (n=291) was 56.7±13.3 years, and most were male (61.9%). A majority of subjects were classified as NYHA Class III HF (56.4%), and most had non-ischemic etiology (65.2%). Two physical symptom clusters (severe physical (26.3%) and mild physical (73.7%); dyspnea t=7.35, p&lt;0.001; wake disturbances t=16.80, p&lt;0.001) and two affective symptom clusters (severe affective (21.2%) and mild affective (78.8%); depression t=22.1, p&lt;0.001; anxiety t=7.87, p&lt;0.001) were identified in a model with good fit (entropy=0.80). Subjects with severe physical symptoms were more likely to have severe than mild affective symptoms, and those with mild physical symptoms were more likely to have mild than severe affective symptoms (χ2=106.8, p&lt;0.001; tau b=0.62). Conclusions: There is a strong association between physical and affective symptom clusters among adults with moderate to advanced HF that may be helpful in identifying adults with HF at risk for multiple, co-occurring symptoms.
Prognostic significance of baseline metabolic tumor volume in relapsed and refractory Hodgkin lymphoma
Authors: Alison J. Moskowitz, Heiko Schöder, Somali Gavane, Katie L. Thoren, Martin Fleisher, Joachim Yahalom, Susan J. McCall, Briana R. Cadzin, Stephanie Y. Fox, John Gerecitano, Ravinder Grewal, Paul A. Hamlin, Steven M. Horwitz, Anita Kumar, Matthew Matasar, Andy Ni, Ariela Noy, M. Lia Palomba, Miguel-Angel Perales, Carol S. Portlock, Craig Sauter, David Straus, Anas Younes, Andrew D. Zelenetz, Craig H. Moskowitz
Journal: Blood (2017)
Haploinsufficiency for DNA methyltransferase 3A predisposes hematopoietic cells to myeloid malignancies
Authors: Christopher B. Cole, David A. Russler-Germain, Shamika Ketkar, Angela M. Verdoni, Amanda M. Smith, Celia V. Bangert, Nichole M. Helton, Mindy Guo, Jeffery M. Klco, Shelly O’Laughlin, Catrina Fronick, Robert Fulton, Gue Su Chang, Allegra A. Petti, Christopher A. Miller, Timothy J. Ley
Journal: Journal of Clinical Investigation (2017)

The gene that encodes de novo DNA methyltransferase 3A (DNMT3A) is frequently mutated in acute myeloid leukemia genomes. Point mutations at position R882 have been shown to cause a dominant negative loss of DNMT3A methylation activity, but 15% of DNMT3A mutations are predicted to produce truncated proteins that could either have dominant negative activities or cause loss of function and haploinsufficiency. Here, we demonstrate that 3 of these mutants produce truncated, inactive proteins that do not dimerize with WT DNMT3A, strongly supporting the haploinsufficiency hypothesis. We therefore evaluated hematopoiesis in mice heterozygous for a constitutive null Dnmt3a mutation. With no other manipulations, Dnmt3a+/– mice developed myeloid skewing over time, and their hematopoietic stem/progenitor cells exhibited a long-term competitive transplantation advantage. Dnmt3a+/– mice also spontaneously developed transplantable myeloid malignancies after a long latent period, and 3 of 12 tumors tested had cooperating mutations in the Ras/MAPK pathway. The residual Dnmt3a allele was neither mutated nor downregulated in these tumors. The bone marrow cells of Dnmt3a+/– mice had a subtle but statistically significant DNA hypomethylation phenotype that was not associated with gene dysregulation. These data demonstrate that haploinsufficiency for Dnmt3a alters hematopoiesis and predisposes mice (and probably humans) to myeloid malignancies by a mechanism that is not yet clear.
Safety and efficacy of current direct‐acting antiviral regimens in kidney and liver transplant recipients with hepatitis C: Results from the HCV‐TARGET study
Authors: Varun Saxena, Vandana Khungar, Elizabeth C. Verna, Josh Levitsky, Robert S. Brown, Mohamed A. Hassan, Mark S. Sulkowski, Jacqueline G. O'Leary, Farrukh Koraishy, Joseph S. Galati, Alexander A. Kuo, Monika Vainorius, Lucy Akushevich, David R. Nelson, Michael W. Fried, Norah Terrault, K. Rajender Reddy
Journal: Hepatology (2017)

Data outside of clinical trials with direct‐acting antiviral regimens with or without ribavirin as treatment of chronic hepatitis C virus in solid organ transplant recipients are limited. Liver transplant (LT), kidney transplant (KT), and dual liver kidney (DLK) transplant recipients from the Hepatitis C Therapeutic Registry and Research Network database, a multicenter, longitudinal clinical care treatment cohort, treated with direct‐acting antiviral regimens between January 1, 2014, and February 15, 2016, were included to assess safety and efficacy. Included were 443 posttransplant patients (KT = 60, LT = 347, DLK = 36); 42% had cirrhosis, and 54% had failed prior antiviral therapy. Most had genotype (GT) 1 (87% with 52% GT1a, 27% GT1b, and 8% GT1 no subtype) and were treated with sofosbuvir (SOF)/ledipasvir ± ribavirin (85%) followed by SOF + daclatasvir ± ribavirin (9%) and ombitasvir/paritaprevir/ritonavir + dasabuvir ± ribavirin (6%). Rates of sustained virologic response (SVR) at 12 weeks were available on 412 patients, and 395 patients (95.9%) achieved SVR at 12 weeks: 96.6%, 94.5%, and 90.9% among LT, KT, and DLK transplant recipients, respectively. Ribavirin did not influence SVR rates and was more often used in those with higher BMI, higher estimated glomerular filtration rate and lower creatinine. Female gender, baseline albumin ≥3.5 g/dL, baseline total bilirubin ≤1.2 mg/dL, absence of cirrhosis, and hepatic decompensation predicted SVR at 12 weeks. Six episodes of acute rejection (n = 2 KT, 4 LT) occurred, during hepatitis C virus treatment in 4 and after cessation of treatment in 2. Conclusion: In a large prospective observational cohort study, direct‐acting antiviral therapy with SOF/ledipasvir, ombitasvir/paritaprevir/ritonavir + dasabuvir, and SOF plus daclatasvir was efficacious and safe in LT, KT, and DLK transplant recipients; ribavirin did not influence SVR, and graft rejection was rare. (H epatology 2017;66:1090‐1101).