tbuckley/cabot-search huggingface dataset:
Abstract 2753: Observation of Long-Term Efficacy and Safety of an ATR12181 Vaccine Against Hypertension in SHR
Authors: Feng Zhu, Yu-Hua Liao, Liudong Li, Yu-miao Wei, Min Wang, Ming Chen, Fen Wei
Journal: Circulation (2006)

Background:  We have established previously that vaccine-ATR12181 could effectively reduce blood pressure (BP) and ameliorated the remodeling of target organs of SHR in 5 months. Long-term efficacy and safety are necessary for the vaccine against hypertension.   Methods and results:  We performed a 16 months long-term observation of the vaccine. Male SHR of 6 weeks age were immunized against the peptide from rat AT 1A  receptor by repeated subcutaneous injections of peptide-tetanus-toxoid complex in combination with Freund’s adjuvant (ATR, n=6). SHR in control group were received 0.9% sodium chloride (Con, n=6). As expect, SHR in ATR group had lower systolic BP than Con group (16 th  month, ATR, 180 ± 6mmHg; Con, 197 ± 4mmHg, P   Conclusion:  The results indicated that long-term vaccination with the vaccine-ATR12181 could effectively reduce BP and reverse remodeling of target organs in SHR, meanwhile vaccine-ATR12181 was safe during the long-term antihypertensive therapy.
A New Concept in the Treatment of Obesity
Authors: Edgar S. Gordon
Journal: JAMA (1963)

OBESITY is a problem of affluent society and occurs only in those geographical areas and during those periods of human history that are characterized by an abundance of food available to great masses of people. Conversely, during war, famine, and economic catastrophe, when food becomes scarce, obesity and related diseases rapidly disappear. At mid-20th century Americans have been made acutely aware that, over many huge, underdeveloped areas of the earth representing more than one half of the world's population, a base subsistence level of food supply or actual famine and starvation are still the "normal" ways of life. Among these people obesity is unknown. In other countries, such as the US and those of western Europe, a superabundance of food has led to a high and continuously rising incidence of obesity. There could be no more eloquent testimony to overeating as the basic cause of this problem. Within any
Rehabilitation after Sensory Neuronopathy Syndrome
Authors: Jonathan Cole
Journal: Journal of the Royal Society of Medicine (1998)

The acute sensory neuronopathy syndrome, first described by Schaumberg et al. in 19791, is amongst the rarest of neuropathies, with around a dozen cases reported. It is also amongst the most selective, affecting only the large myelinated sensory fibres of the body (and in some cases the lower trigeminal nerve), leaving patients with intact pain and temperature sensation and motor nerve function but without touch and movement/joint position sense over the trunk and limbs. The responses of individuals with this condition allow insights not only into neurophysiological function but also into the ways in which patients mitigate the effects of such profound and irreversible neurological damage.
Phase II Trial of SBRT for Stage I NSCLC: Survival, Local Control, and Lung Function at 36 Months
Authors: Arturo Navarro-Martin, Samantha Aso, Jon Cacicedo, Maria Arnaiz, Valentin Navarro, Samuel Rosales, Rodolfo de Blas, Ricard Ramos, Ferran Guedea
Journal: Journal of Thoracic Oncology (2016)
IL-7 primes IL-17 in mucosal-associated invariant T (MAIT) cells, which contribute to the Th17-axis in ankylosing spondylitis
Authors: Eric Gracey, Zoya Qaiyum, Ibrahim Almaghlouth, Daeria Lawson, Susan Karki, Naga Avvaru, Zhenbo Zhang, Yuchen Yao, Vidya Ranganathan, Yuriy Baglaenko, Robert D Inman
Journal: Annals of the Rheumatic Diseases (2016)

Ankylosing spondylitis (AS) is a chronic inflammatory disease of unknown origin in which interleukin (IL) 17 has been genetically and therapeutically recognised as a key player. Identification of the cellular sources and inducers of IL-17 is crucial in our understanding of the drivers of inflammation in AS. Recently, mucosal-associated invariant T (MAIT) cells have been implicated in autoimmune diseases. Their gut origin, effector phenotype and expression of multiple AS-associated genes, such as IL7R and IL23R, makes them potential contributors to the pathogenesis of AS.Mononuclear cells from patients with AS, healthy controls (HCs) and patients with rheumatoid arthritis were isolated from blood and synovial fluid (SF). Flow cytometry was used to identify MAIT cells. Phenotype was assessed by intracellular staining for cytokines and granzyme. Function was assessed by antigen-specific stimulation using Salmonella, or antigen non-specific activation via priming with IL-7 or IL-23.MAIT cells were reduced in frequency in the blood of patients with AS compared with HCs, yet patients with AS had an elevated frequency IL-17A+ MAIT cells. There was an enrichment of MAIT cells in SF, which had an exaggerated IL-17 phenotype. IL-17 elevation in AS MAIT cells was dependent on priming with IL-7 but not IL-23 or antigen stimulation. The AS-associated IL7R single nucleotide polymorphism (SNP), rs11742270, had no effect on IL-7R expression or function in the experiments performed.This study reveals a potential role for MAIT cells in patients with AS and is the first linking IL-7 to the elevated IL-17 profile in patients through the AS-associated risk gene IL7R.
EPID-28PROGNOSTIC AND PREDICTIVE BIOMARKERS IN RECURRENT WHO GRADE 3 GLIOMA PATIENTS TREATED WITH BEVACIZUMAB AND IRINOTECAN
Authors: Anders Toft, Thomas Urup, Kirsten Grunnet, Ib Jarle Christensen, Signe Regner Michaelsen, Helle Broholm, Babloo Lukram, Vibeke André Larsen, Michael Kosteljanetz, Ulrik Lassen, Hans Skovgaard Poulsen
Journal: Neuro-Oncology (2015)

BACKGROUND: Bevacizumab, a monoclonal antibody targeting vascular endothelial growth factor A (VEGF-A) has shown activity in the treatment of recurrent malignant glioma. Predictive markers and prognostic models are required in order to individualize treatment for grade 3 glioma patients. The primary endpoint of this study was to identify predictive biomarkers associated with response to bevacizumab therapy. The secondary endpoint was to identify prognostic factors associated with progression-free survival (PFS) and overall survival (OS). METHODS: A total of 62 consecutive, recurrent grade 3 glioma patients were administered bevacizumab and irinotecan between December 2005 and November 2014 according to a previously published clinical protocol. A wide range of clinical, histopathological and molecular factors were screened for significant correlation (p < 0.05) with response and survival endpoints using logistic and Cox regression, respectively. Potentially predictive biomarkers were subjected to multivariate analysis. The landmark method was employed for analysis of survival by response. RESULTS: Twenty-two of 57 evaluable patients (38.6 %) demonstrated a response at the time of their best response MRI (RANO criteria). Responders had significantly prolonged OS (p = 0.007) and trended toward longer PFS (p = 0.067) as compared to non-responders (OS: 12.4 vs 4.3 months, PFS: 5.6 vs 3.2 months). A favorable WHO performance status (PS) and absence of necrosis were significantly more common in responders than non-responders. Multivariate analysis also identified a poor PS as the only prognostic factor for PFS, while an unfavorable PS and immunohistochemical p53 accumulation were prognostic of reduced OS. CONCLUSIONS: A poor baseline PS and the presence of necrosis were negatively associated with response to bevacizumab. An unfavorable PS and p53 positivity are prognostic of worse outcome in this patient population.
Mesalazine Changes Apoptosis and Proliferation in Normal Mucosa of Patients with Sporadic Polyps of the Large Bowel
Authors: A. Reinacher-Schick, F. Seidensticker, S. Petrasch, M. Reiser, S. Philippou, D. Theegarten, G. Freitag, W. Schmiegel
Journal: Endoscopy (2000)

Regular intake of nonsteroidal anti-inflammatory drugs (NSAIDs) may reduce the occurrence of colorectal adenoma and carcinoma, possibly by inducing apoptosis and/or decreasing proliferation in colorectal epithelial cells. Mesalazine is widely used in the treatment of patients with inflammatory bowel disease, and well tolerated. We investigated its effect on apoptosis and proliferation of colorectal mucosa in 21 patients with sporadic polyps of the large bowel.In total, 17 patients with sporadic colorectal polyps (> or = 5 mm) underwent polypectomy and biopsy of uninvolved mucosa before and after treatment with 1 g/d mesalazine for 1, 3, 7 or 14 days. Four additional patients served as untreated controls. Apoptotic index (AI) was measured by terminal deoxynucleotidyl transferase-mediated d-uridine triphosphate nick-end labeling (TUNEL) assay; proliferation index (PI) was measured by immunohistochemical examination with anti-Ki67 antibody.AI was significantly increased 1 and 3 days after initiation of treatment with mesalazine compared with controls (P= 0.0107 for the 1-day treatment group and P=0.0142 for the 3-day treatment group), and seemed to remain largely unchanged after longer treatment duration. Proliferation appeared to be decreased by mesalazine in all treatment groups, while proliferation in controls did not change (P=0.0107 for the 1-day treatment group and P= 0.0142 for the 3-day treatment group compared with controls.Mesalazine significantly induces apoptosis and decreases proliferation in colorectal mucosa in patients with sporadic polyps of the large bowel. This may be clinically relevant in that it may lower the rate of polyp recurrence after polypectomy, thereby possibly contributing to the chemoprevention of sporadic colorectal carcinoma.
Neuroendocrine differentiation: a prognostic feature of non-small-cell lung cancer?
Authors: S B Baylin
Journal: Journal of Clinical Oncology (1989)

Article Tools Article Tools OPTIONS & TOOLS Export Citation Track Citation Add To Favorites Rights & Permissions COMPANION ARTICLES No companion articles ARTICLE CITATION DOI: 10.1200/JCO.1989.7.10.1375 Journal of Clinical Oncology - published online before print September 22, 2016 PMID: 2550589 Neuroendocrine differentiation: a prognostic feature of non-small-cell lung cancer? S B BaylinxS B BaylinSearch for articles by this author https://doi.org/10.1200/JCO.1989.7.10.1375 PDF "Neuroendocrine differentiation: a prognostic feature of non-small-cell lung cancer?." Journal of Clinical Oncology, 7(10), pp. 1375–1376© 1989 by American Society of Clinical Oncology
In-Hospital Mortality after Surgical Lung Biopsy for Interstitial Lung Disease in the United States. 2000 to 2011
Authors: John P. Hutchinson, Andrew W. Fogarty, Tricia M. McKeever, Richard B. Hubbard
Journal: American Journal of Respiratory and Critical Care Medicine (2015)

Rationale: Surgical lung biopsy can help to determine a specific diagnosis in interstitial lung disease but has associated risks. Most currently available mortality data are derived from case series and may not be generalizable to broader populations.Objectives: To assess in-hospital mortality after surgical lung biopsy for interstitial lung disease in a national secondary care dataset from the United States.Methods: Data were obtained from the 2000–2011 Nationwide Inpatient Sample. Cases were identified using International Classification of Diseases codes for interstitial lung disease and surgical lung biopsies. Lung resections and cases of lung cancer were excluded. Weighted data were used to estimate numbers of biopsies nationwide and in-hospital mortality, and multivariable logistic regression was used to adjust for sex, age, geographic region, comorbidity, type of operation, and provisional diagnosis.Measurements and Main Results: We estimated there to be around 12,000 surgical lung biopsies performed annually for interstitial lung disease in the United States, two-thirds of which were performed electively. In-hospital mortality was 1.7% for elective procedures but significantly higher for nonelective procedures (16.0%). Male sex, increasing age, increasing comorbidity, open surgery, and a provisional diagnosis of idiopathic pulmonary fibrosis or connective tissue disease–related interstitial lung disease were risk factors for increased mortality.Conclusions: In-hospital mortality after elective surgical lung biopsy for interstitial lung disease is just under 2% but significantly higher for nonelective procedures. Identified risk factors for death should be taken into account when counseling patients on whether to pursue a histologic diagnosis.
Transplantable Calcitonin-Secreting Medullary Carcinomas of the Thyroid in the WAG/Rij Rat
Authors: G. A. Boorman, J. N. M. Heersche, C. F. Hollande
Journal: JNCI Journal of the National Cancer Institute (1974)

Bioassay of medullary thyroid carcinomas occurring spontaneously in older WAG/Rij rats revealed high levels of calcitonin activity in the tumor tissue. Of 10 such spontaneous carcinomas transplanted toyoung WAG/Rij recipients, 7 grew. Several transplantation lines are being maintained. The tumors usually grew slowly and progressively. The hosts died 7–11 months after receiving the transplant, often from an adenoma of the pituitary. Calcitonin activity has been demonstrated both in the tumor transplant and in the serum of the tumor-bearing rats. In a preliminary experiment, calcitonin secretion by tumor tissue in vitro was stimulated by addition of pentagastrin.
NGR-hTNF plus chemotherapy as first-line therapy of non-small cell lung cancer (NSCLC).
Authors: Vanesa Gregorc, Nicoletta Zilembo, Francesco Grossi, Tommaso M De Pas, Gilda Rossoni, Filippo Pietrantonio, Erika Rijavec, Monica Giovannini, Giovanni Citterio, Antonio Lambiase, Claudio Bordignon
Journal: Journal of Clinical Oncology (2012)

7581 Background: NGR-hTNF (asparagine-glycine-arginine human tumor necrosis factor) is a selective vascular targeting agent able to improve intratumoral chemotherapy uptake. Methods: Chemo-naive, stage IIIb-IV NSCLC patients (pts), stratified by histology (nonsquamous or squamous) and PS (0 or 1), were randomized to cisplatin 80 mg/m 2 /day(d)1 plus either pemetrexed 500 mg/m 2 /d1 (nonsquamous) or gemcitabine 1,250 mg/m 2 /d1+8 (squamous) every 3 weeks (q3w) up to 6 cycles with (arm A) or without (arm B) NGR-hTNF 0.8 μg/m 2 /d1 q3w until progression. Progression free survival (PFS) was primary end point of this phase 2 trial (β=20%, α=20%, HR=0.62, and n=102). Secondary end points included adverse events (AEs), response rate (RR) and overall survival (OS). Results: 59 pts were assigned to arm A and 57 to arm B. Baseline characteristics in arm A/B were: median age 62/63; male 34/37; PS 1 21/21; squamous 15/15; nonsmokers 14/12; EGFR mutations 5/5. For the nonsquamous group, 281 cycles (mean 6.5; range 1-18) were given in arm A and 190 (mean 4.7; range 1-6) in arm B, while for the squamous group, 88 (mean 6.3; range 1-19) in arm A and 48 (mean 3.7; range 1-6) in arm B. Most common grade 3/4 AEs were neutropenia 14% vs 17% and fatigue 7% vs 11% in arm A and B, respectively. No grade 3/4 AEs related to NGR-hTNF or bleeding in pts with squamous histology were noted. Median follow-up was 12.4 months. In the whole study population, median (m)PFS was 5.8 vs 5.7 months (HR=0.95), RR was 23% vs 19%, and 1-year OS was 62% vs 62% in arm A and B, respectively. In the nonsquamous subset, a trend toward longer mPFS in arm A compared to arm B was noted in pts with a PS of 1 (6.7 vs 4.6 months, respectively), nonsmoking history (6.2 vs 3.4), younger age (6.5 vs 3.4), and EGFR mutations (7.2 vs 3.3). In the squamous subset, mPFS was 5.1 vs 3.9 months (HR=0.71) and mOS was 14.2 vs 10.8 months (HR=0.73) in arm A and B, respectively. In these pts, ORR was 36% in arm A and 23% in arm B, while median changes from baseline in target tumor size after 2, 4, and 6 cycles were -29%, -45%, and -41%, respectively in arm A, and -18%, -22%, and -14%, respectively in arm B. Conclusions: Regardless of histology, NGR-hTNF can be safely given with standard chemotherapy, showing tolerability and hint of activity in squamous NSCLC.
Father’s age and lifestyle link to birth defects in offspring, review finds
Authors: Susan Mayor
Journal: BMJ (2016)

A father’s age, alcohol use, and exposure to environmental factors have been linked by increasing research evidence to birth defects in his offspring, a review has found, suggesting that these defects result from epigenetic alterations that can potentially affect several generations.1

The review’s authors, led by Joanna Kitlinska, of Georgetown University in Washington, DC, USA, said, “Historically, research into congenital defects has focused on maternal impacts on the fetal genome during …
Photothermal Therapy: Cancer Cell Internalization of Gold Nanostars Impacts Their Photothermal Efficiency In Vitro and In Vivo: Toward a Plasmonic Thermal Fingerprint in Tumoral Environment (Adv. Healthcare Mater. 9/2016)
Authors: Ana Espinosa, Amanda K. A. Silva, Ana Sánchez‐Iglesias, Marek Grzelczak, Christine Péchoux, Karine Desboeufs, Luis M. Liz‐Marzán, Claire Wilhelm
Journal: Advanced Healthcare Materials (2016)

Because the ultimate target for photothermal therapy is the cancer cell, heating performances must be evaluated intracellularly. On page 1040 C. Wilhelm and team provide the first in vitro and in vivo photothermal measurements in cancer cells with gold nanostars. They demonstrate that once nanostars are internalized within endosomes, heat generation can change significantly.
Abstract 13973: Circulating Eicosapentaenoic Acid to Oleic Acid Ratio and Risk for Cardiovascular Events in Patients With Coronary Artery Disease; Sub-analysis of SHINANO Registry
Authors: Hirofumi Hioki, Takashi Miura, Yusuke Miyashita, Souichirou Ebisawa, Hirohiko Motoki, Atsushi Izawa, Jun Koyama, Uichi Ikeda
Journal: Circulation (2015)

Background: Until now, Omega-3/Omega-6 polyunsaturated fatty acid (PUFA) ratio, particularly in ratio of eicosapentaenoic acid (EPA) to arachnidonic acid (AA), has been reported to associate with the incidence of cardiovascular events. However, the clinical impact of monounsaturated fatty acid (MUFA) on cardiovascular events has not been well understood. Objective: In this study, we evaluate whether ratio of MUFA to PUFA, especially EPA/Oleic acid (OA), could predict clinical outcome in patients with coronary artery disease (CAD) who underwent percutaneous coronary intervention (PCI). Methods: SHINANO registry was prospective, observational, multicenter cohort study, enrolling 1,923 consecutive patients with CAD. From this registry, we identified 182 patients who measured fatty acid on admission. We stratified according to median of EPA/OA ratio. The primary endpoint was net adverse clinical events (NACE) including cardiac death, nonfatal myocardial infarction, ischemic stroke, PCI for ACS, heart failure, and major bleeding (Bleeding Academic Research Consortium II-IV) for 1-years. Results: Mean age was 72±10 years, 24% female, and 27% was acute coronary syndrome. One-years follow-up was completed in 181 patients (99.5%). Cumulative incidence of NACE was 22 cases. In Kaplan-Meier analysis, incidence of NACE was significantly higher in patients with EPA/OA of 0.03 to 0.12 compared to 0.13 to 0.54 (16.6% vs. 6.6%, Log-rank p=0.025). After adjusting for the calculated propensity score for EPA/OA ≥ 0.13 or not, EPA/OA ≥ 0.13 was remained an independent predictor of NACE (hazard ratio, 0.36; 95% confidence interval [CI], 0.14-0.96; p-value 0.042). The ROC curve of EPA/OA for NACE demonstrated that the area under the ROC curve (ACU) was 0.73 (95% CI; 0.61-0.85). Conclusions: This study firstly demonstrated that the patients with high EPA/OA ratio would have low incidence of NACE in patients with CAD who underwent PCI.
North American Multicenter Volumetric CT Study for Clinical Staging of Malignant Pleural Mesothelioma: Feasibility and Logistics of Setting Up a Quantitative Imaging Study
Authors: Ritu R. Gill, David P. Naidich, Alan Mitchell, Michelle Ginsberg, Jeremy Erasmus, Samuel G. Armato, Christopher Straus, Sharyn Katz, Demetrois Patios, William G. Richards, Valerie W. Rusch, Valerie Rusch, Michelle Ginsberg, David Rice, Jeremy Erasmus, Harvey Pass, David Naidich, Hedy L. Kindler, Samuel Armato, Christopher Straus, Wickii Vigneshwaran, Joseph Friedberg, Sharyn Katz, Marc de Perrot, Demetrios Patios, Dori Giroux, Lynn Shemanski, Alan Mitchell, William G. Richards, Ritu R. Gill
Journal: Journal of Thoracic Oncology (2016)

BackgroundClinical tumor (T), node, and metastasis staging is based on a qualitative assessment of features defining T descriptors and has been found to be suboptimal for predicting the prognosis of patients with malignant pleural mesothelioma (MPM). Previous work suggests that volumetric computed tomography (VolCT) is prognostic and, if found practical and reproducible, could improve clinical MPM classification.MethodsSix North American institutions electronically submitted clinical, pathologic, and imaging data on patients with stages I to IV MPM to an established multicenter database and biostatistical center. Two reference radiologists blinded to clinical data independently reviewed the scans; calculated clinical T, node, and metastasis stage by standard criteria; performed semiautomated tumor volume calculations using commercially available software; and submitted the findings to the biostatistical center. Study end points included the feasibility of a multi-institutional VolCT network, concordance of independent VolCT assessments, and association of VolCT with pathological T classification.ResultsOf 164 submitted cases, 129 were evaluated by both reference radiologists. Discordant clinical staging of most cases confirmed the inadequacy of current criteria. The overall correlation between VolCT estimates was good (Spearman correlation 0.822), but some were significantly discordant. Root cause analysis of the most discordant estimates identified four common sources of variability. Despite these limitations, median tumor volume estimates were similar within subgroups of cases representing each pathological T descriptor and increased monotonically for each reference radiologist with increasing pathological T status.ConclusionsThe good correlation between VolCT estimates obtained for most cases reviewed by two independent radiologists and qualitative association of VolCT with pathological T status combine to encourage further study. The identified sources of user error will inform design of a follow-up prospective trial to more formally assess interobserver variability of VolCT and its potential contribution to clinical MPM staging.
Magnesium sulphate and pre-eclampsia
Authors: L. Duley, J. P Neilson
Journal: BMJ (1999)

<h3>Objective:</h3> To investigate the expression of α-synuclein in colonic biopsies of patients with idiopathic REM sleep behavior disorder (iRBD) and address if α-synuclein immunostaining of tissue obtained via colonic biopsies holds promise as a diagnostic biomarker for prodromal Parkinson disease (PD). <h3>Methods:</h3> Patients with iRBD, patients with PD, and healthy controls were prospectively recruited to undergo colonic biopsies for comparison of α-synuclein immunoreactivity patterns between the groups by using 2 different antibodies. <h3>Results:</h3> There was no difference in colonic mucosal and submucosal immunostaining between groups using the 15G7 α-synuclein antibody, which was found in almost all participants enrolled in this study. By contrast, immunostaining for serine 129-phosphorylated α-synuclein (pSyn) in submucosal nerve fibers or ganglia was found in none of 14 controls but was observed in 4 of 17 participants with iRBD and 1 out of 19 patients with PD. <h3>Conclusions:</h3> The present findings of pSyn immunostaining of colonic biopsies in a substantial proportion of iRBD participants raise the possibility that this tissue marker may be a suitable candidate to study further as a prodromal PD marker in at-risk cohorts.