tbuckley/cabot-search huggingface dataset:
Abstract LB-092: Programmed death-ligand 1 is overexpressed in bronchial preneoplastic lesions: can it be a risk indicator
Authors: Hee Sun Park, Bo Mi Park, Dong Il Park, Chung Jae Uk, Jae Young Moon, Jung Sung Soo, Choong Sik Lee, Ju Ock Kim, Sun Young Kim, Jaseok Peter Koo
Journal: Cancer Research (2015)

Abstract Compared to the vigorous development of targeted drugs and some of them are already become one of the best treatment of choices in lung adenocarcinoma, squamous lung carcinoma has no definite targets and treatment outcome is not yet superior to lung adenocarcinoma. Demonstration of initial carcinogenesis is benefitial in two aspects: cancer prevention and development of its targets. Studying preneoplastic lesions of bronchus can answer those questions. Preneoplastic lesion, which is considered to have malignant potential, may develop into invasive cancer by escaping from host immune response. CD274 (programmed death-ligand 1, PD-L1) interacts with PD-1, is known to inhibit CD8+ cytotoxic T lymphocyte and induce apoptosis and, also to promote the differentiation of CD4+ T cells into regulatory T cells, so finally evade immune surveillance. We hypothesized that PD-L1 may work as an immune evader in preneoplastic lesion during its carcinogenesis. We performed white light and/or autofluorescence bronchoscopy in patients who have risk factor(s) of lung cancer or are suspected to have a lung cancer. Interestingly, PD-L1 was also overexpressed in preneoplastic lesions especially in severe dysplasia of the bronchus. This finding implies overexpression of PD-L1 can involve at early step of carcinogenesis. Further studies are needed to demonstrate the role of PD-L1 in preneoplastic bronchial lesion potential to develop invasive cancer. Citation Format: Hee Sun Park, Bo Mi Park, Dong Il Park, Chung Jae Uk, Jae Young Moon, Jung Sung Soo, Choong Sik Lee, Ju Ock Kim, Sun Young Kim, Jaseok Peter Koo. Programmed death-ligand 1 is overexpressed in bronchial preneoplastic lesions: can it be a risk indicator. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr LB-092. doi:10.1158/1538-7445.AM2015-LB-092
Potential Economic Impact of Using a Restrictive Transfusion Trigger Among Patients Undergoing Major Abdominal Surgery
Authors: Aslam Ejaz, Steven M. Frank, Gaya Spolverato, Yuhree Kim, Timothy M. Pawlik
Journal: JAMA Surgery (2015)

Transfusion practice among surgeons varies despite several evidence-based recommendations supporting the restrictive use of blood products.To define the economic impact of liberal blood transfusions as assessed through an analysis of hemoglobin (Hb) triggers.Using a prospective database, data on Hb levels that triggered a transfusion and overall blood product use were obtained for patients undergoing pancreas, liver, or colorectal surgery between January 1, 2010, and August 31, 2013, at Johns Hopkins Hospital. An economic analysis was performed using a range of costs for a single unit of packed red blood cells (PRBCs) based on actual institutional acquisition costs ($220/unit) and an estimated activity-based cost ($760/unit). Guidelines define a liberal Hb trigger as transfusion of PRBCs for an intraoperative Hb level of 10 g/dL or greater or a postoperative Hb level of 8 g/dL or greater (to convert to grams per liter, multiply by 10.0).Numbers of surgical patients who received PRBC transfusion, estimated cost per transfusion, and estimated cost of excessive blood transfusions.Among 3027 patients, 942 (31.1%) received at least 1 PRBC transfusion, intraoperatively in 264 patients (8.7%), postoperatively in 429 (14.2%), or both in 249 (8.2%). A total of 4000 units of PRBCs (range, 0-167 units/patient) were transfused in the intraoperative (1581 units [39.5%]) and postoperative (2419 units [60.5%]) periods. Estimated total costs of PRBC transfusion ranged from $880,000 to $3,040,000, with marked variation in costs per patient across procedure type and surgeon. Among the 942 patients who received a transfusion, 456 units (11.4%) were transfused using a liberal trigger (intraoperative, 122 patients [13.0%]; postoperative, 79 patients [8.4%]). By adopting a restrictive trigger, total overall PRBC transfusion costs may have been reduced by $100,320 to $346,560 during the 44-month study period or $27,360 to $94,516 per year for patients undergoing a pancreas, liver, or colorectal resection.More than 1 in 10 units of PRBCs were transfused using a liberal Hb trigger. Patient blood management programs should aim to identify and reduce liberal transfusion practice in the surgical patient.
MicroRNA-29c and 223 Are Powerful Prognostic Factors for Chronic Lymphocytic Leukemia and Improve Risk Stratification When Combined with ZAP70 and LPL in a qPCR Score.
Authors: Basile Stamatopoulos, Nathalie Meuleman, Dominique Bron, Benjamin Haibe-Kains, Pascale Saussoy, Philippe Martiat, Laurence Lagneaux
Journal: Blood (2008)
Adaptive developmental plasticity might not contribute much to the adaptiveness of reproductive strategies
Authors: Lars Penke
Journal: Behavioral and Brain Sciences (2009)

Abstract Del Giudice's model belongs among those that highlight the role of adaptive developmental plasticity in human reproductive strategies; but at least three other forms of evolutionary adaptation also influence reproductive behavior. Similar to earlier models, the existing evidence suggests that Del Giudice's hypothesized effects are rather weak. In particular, adult attachment styles are hardly predictive of outcomes visible to natural selection.
NT-Probnp levels to perspectively assess acut cardiac failure after adjuvant doxorubicine therapy in early breast cancer patients
Authors: T. Cil, A. Altintas, S. Pasa, M. A. Kaplan, S. Alan, A. Isikdogan
Journal: Journal of Clinical Oncology (2008)

13541 Background: Anthracyclines are well established as highly efficacious antineoplastic agents for various hemopoietic and solid tumors such as in breast cancer. Radionuclide angiocardiography and two-dimensional echocardiography are extensively used in monitoring for early anthracycline-induced cardiotoxicity on the basis of its proven value in reducing the incidence of cardiac failure from early anthracycline cardiotoxicity. The aim of this prospective study, was to document the association with the plasma levels of N-terminal pro-brain natriuretic peptide (NT-proBNP) in breast cancer patients with adjuvan anthracycline treatment. Patients and Methods: Newly diagnosed thirty-three early breast cancer patients who received total 240 mg/m2 doxorubicin as parts of adjuvan chemotherapy after curative breast surgery were included in this study. Results: NT-pro BNP levels were significantly higher in low systolic ejection fraction patients who had normal ejection fraction levels before doxorubicine therapy (p=0,020) (Table). No difference was demonstrated in cardiac systolic ejection fraction after doxorubine CT between the patients who had high and normal NT-pro BNP levels before doxorubine CT. None of the factors that were studied (grade, ER, PgR, HER-2, age), was found to be significantly related to NT- proBNP. Conclusion: Anthracyclin chemotherapy is a widely-used and effective treatment for breast cancer. Its use is limited by associated progressive and clinically significant cardiotoxic effects. N-terminal proBNP have been shown to be sensitive markers in predicting early cardiac dysfunction and their plasma levels are significantly elevated in patients with heart failure. The association of higher NT-pro BNP levels with reduced cardiac ejection fraction in breast cancer patients after anthracycline administration could be an early indication of cardiotoxicity. No significant financial relationships to disclose.
Neurochemical abnormalities of anorexia nervosa and bulimia nervosa
Authors: M Fava, P M Copeland, U Schweiger, D B Herzog
Journal: American Journal of Psychiatry (1989)

The authors review the research on anorexia nervosa and bulimia nervosa, emphasizing the neurotransmitters and neuromodulators that regulate eating behavior. Anorexia nervosa is associated with changes in the noradrenergic, serotonergic, and opioid systems; bulimia nervosa is accompanied by marked alterations in serotonin and norepinephrine activity. These neurochemical changes may perpetuate pathological eating behavior and may be responsible for several associated psychiatric symptoms, including anxiety and depression. The authors also summarize studies of several drugs that are used in the treatment of eating disorders and are known to modify neurotransmitter activity. Understanding the neurochemistry of eating disorders seems crucial for the rational development of both psychopharmacological and behavioral treatments.
Hepatic Mitochondrial Pyruvate Carrier 1 Is Required for Efficient Regulation of Gluconeogenesis and Whole-Body Glucose Homeostasis
Authors: Lawrence R. Gray, Mst Rasheda Sultana, Adam J. Rauckhorst, Lalita Oonthonpan, Sean C. Tompkins, Arpit Sharma, Xiaorong Fu, Ren Miao, Alvin D. Pewa, Kathryn S. Brown, Erin E. Lane, Ashley Dohlman, Diana Zepeda-Orozco, Jianxin Xie, Jared Rutter, Andrew W. Norris, James E. Cox, Shawn C. Burgess, Matthew J. Potthoff, Eric B. Taylor
Journal: Cell Metabolism (2015)
Carboplatin/Ifosfamide Window Therapy for Osteosarcoma: Results of the St Jude Children’s Research Hospital OS-91 Trial
Authors: William H. Meyer, Charles B. Pratt, Catherine A. Poquette, Bhaskar N. Rao, David M. Parham, Neyssa M. Marina, Alberto S. Pappo, Hazem H. Mahmoud, Jesse J. Jenkins, James Harper, Michael Neel, Barry D. Fletcher
Journal: Journal of Clinical Oncology (2001)

PURPOSE: To determine the activity of carboplatin/ifosfamide in patients with previously untreated osteosarcoma and to estimate patient outcomes after a multiagent chemotherapy protocol that eliminated cisplatin. PATIENTS AND METHODS: Sixty-nine patients with newly diagnosed, previously untreated osteosarcoma received three cycles of carboplatin (560 mg/m 2 × 1) and ifosfamide (2.65 g/m 2 /d × 3). Assessment of response was evaluated after two (week 6) and three (week 9) chemotherapy cycles. At week 9, histologic response was assessed. Adjuvant therapy comprised two additional carboplatin/ifosfamide cycles, doxorubicin, and high-dose methotrexate. Patients were stratified at enrollment: stratum A, resectable primary tumor without metastases; stratum B, unresectable primary tumor; and stratum C, metastatic disease at diagnosis. Week 6 response was compared with that of a historic group that received only ifosfamide during the initial window evaluation. RESULTS: The clinical and radiographic response rate to three cycles of carboplatin/ifosfamide was 67.7% (95% confidence interval, 55.0% to 78.8%). Compared with the historic population who received only ifosfamide, the combination of carboplatin and ifosfamide reduced the progressive disease rate at week 6 (31.9% v 9%, P = .003). For patients in stratum A, the 3-year event-free survival and survival were 72.3% ± 6.7% and 76.4% ± 6.4%, respectively. Patients who received carboplatin-based therapy had less long-term renal toxicity and ototoxicity. CONCLUSION: This pilot trial suggests that carboplatin/ifosfamide combination chemotherapy has substantial antitumor activity. In the context of a multiagent chemotherapy protocol comprising high-dose methotrexate and doxorubicin, we found that the addition of carboplatin/ifosfamide resulted in patient outcomes comparable to trials using cisplatin-based therapy with less long-term toxicity.
LSC 2013 abstract - Regulation of microRNAs in response to herpes simplex virus type-1 (HSV-1) infection in idiopathic pulmonary fibrosis (IPF): Preliminary results
Authors: Eliza Tsitoura, Katerina Antoniou, Anna Psaraki, Ismini Lasithiotaki, Demetrios Spandidos, Nikolaos Siafakas, George Sourvinos
Journal: European Respiratory Journal (2013)

We have showed that primary cell cultures of IPF patients were permissive to HSV-1 in vivo.Information on the miRNA profiles in bronchoalveolar lavage fluid(BALF) in IPF remains scarce.Our study was focused on the BALF of IPF patients and the expression patterns of several miRNAs previously implicated in fibrogenesis. We have also examined the changes in the miRNA expression patterns of BAL cells induced by HSV-1 infection.Methodology:TaqMan miRNA assays were used to analyse the expression of miRNAs from total RNA isolated from IPF BALFs and controls.miRNAs demonstrating the lowest variability across samples and between control and IPF groups were selected using the NormFinder algorithm for normalization of miRNA expression and were validated with REST2009. Analysis of miRNA relative expression was performed using REST2009 algorithm. BALF cells were infected with the 17syn strain of HSV-1 for 1, 3 and 8 hrs and miRNA expression was analysed. TNF-α and IL-6 levels were finally determined in the supernatants of HSV-1 infected BALF primary cultures.Results: Preliminary analyses on IPF (n=5) and control (n=4) BALF cells revealed that among the miRNAs which are differentially regulated between IPF and control groups, miR-210 were significantly upregulated whereas miR-29c and miR-185 were downregulated in IPF samples. HSV-1 infection of BAL cells from IPF patients (n=3), resulted in the downregulation of miR-29b and the upregulation of miR-155 in 2 out of 3 cases whereas TNF-α and IL-6 cytokine expression was also induced by HSV-1 infection.Conclusions: HSV-1 seems capable to enhance the profibrotic patterns in IPF BALF cells.
Direct to consumer advertising of prescription drugs
Authors: Jerome R Hoffman, Michael Wilkes
Journal: BMJ (1999)

Direct to consumer (DTC) advertising of prescription drugs is expanding dramatically in the United States, and there is some sentiment in favour of allowing this practice to come to the United Kingdom.1 Such advertising is a powerful tool, designed to create a demand, in order to maximise profits. Extending the scope of already ubiquitous promotions about “post-nasal drip,” “unsightly rashes,” or “cures” for baldness has little to do with educating patients or relieving suffering. It will, however, inevitably drain healthcare dollars, dramatically increase unnecessary prescribing, and strain patient-doctor relationships.

Typical direct to consumer advertising for prescription drugs in the US consists of glossy promotional materials suggesting that the advertised product represents a major medical advance, accompanied (because of Federal Drug Administration regulations, and over the objections of the pharmaceutical industry) by tiny print “information” presented in medical jargon which virtually no consumers can understand. 1 2 These advertisements—whose “rules for doing DTC right” include “always focus on benefits, not problems”3 …
Knowledge, attitude and practice of smoking and lung cancer
Authors: Subir Kumar Dey
Journal: European Respiratory Journal (2013)

BACKGROUND: Lung cancer(Primary) commonest cancer in the world,50% of these are occurring in developing countries now, mostly due to smoking.However 15% in males(M) & 55% in females(Fe) are not due to smoking ,with neversmokers(NS) accounting for 25%. In West, M & Fe smoke with equal frequency, a shift in histological types of lung cancer is occurring with a decline in Squamous cell carcinoma(SqCC) and a surge of Adenocarcinoma(AdC), predominating in Fe – NS & in M- NS.  OBJECTS: Pattern of lung cancer in eversmokers (ES) & NS in Eastern India, % of people who smoked despite knowing its harmful effects.  METHODS: Primary Lung cancer diagnosed adults in Chest Medicine,CNMC,2009-2012.  RESULTS: 132 cases mean 57.9 yrs(Range 30-88 yrs),M-107.Cough 86.36%,Chest pain 72.72%,Dyspnea61.36%,Hemoptysis46.21%H ES – 113 (M 102) &NS 19 (M 5).Mean packyear-M-24.87&Fe 12.4.  Among ES commonest type of lung cancer was NSCLC 95/113 (84.07%) SqCC (37/58) the commonest followed by AdC(17/58)& Others .SCLC was 14/113.NS 19/132 contributed 14.39% of all lung cancers. AdCC - commonest type 8/19&higher in Fe 6/8 followed by SqCC .Against a background of 70% literacy level, majority 85.8 % (97/113, M 93/102 and Fe 4/11) continued smoking despite knowing its health hazards thereby questioning the effectiveness of warning advertisements on cigarette/ bidi packets.  CONCLUSION: Though the no of subjects in our study was small,the shift in current histological patterns in our study matches the current global data. Of 85.8% ES who continued smoking despite knowing its hazards,significantly more M than Fe have done this (p=0.000 – Chisquare test ,Yates corrected ± 24.54,DF=1).
Abstract 16834: Assessment of The Pharmacological Response to Aspirin by Quantitation of Platelet Cyclooxygenase Acetylation.
Authors: Xuanwen Li, Fries Susanne, Emanuela Ricciotti, John A Lawson, Ian A Blair, Garret A FitzGerald, Tilo Grosser
Journal: Circulation (2010)

Aspirin inhibits platelet activity irreversibly by covalent acetylation of cyclooxygenase-1 (COX-1). Variable non-responsiveness to aspirin has been reported based on clinical outcome measures, pla...
Effect of positive expiratory pressure (PEP) on breathing pattern characteristics in cystic fibrosis children
Authors: Lucien Gualdi, Rêncio Bento Florêmcio, Sílvia Brilhante, Vanessa Resqueti, Armele Dornelas de Andrade, Andrea Aliverti, Guilherme Fregonezi
Journal: European Respiratory Journal (2014)

Objective : to evaluate the effects of different levels of PEP in cystic fibrosis (CF) children breathing pattern. Methods : 8 patients with CF (12±2.7 years, FVC%: 84.3±17.5, FEV1/FVC%: 68.2±12) and 7 age-matched healthy controls (CG) with normal lung function were included in the study. Ventilatory parameters were assessed by Optoelectronic Plethysmography during 3 minutes of quite breathing (QB) and 3 minutes breathing against different levels of PEP (10, 15 and 20 cmH2O). Results : chest wall tidal volume (VTCW) was significantly increased during the use of PEP compared to QB in both groups and significantly higher in CG compared to CF at PEP20 cmH2O (0.44±0.16 vs. 0.77±0.26; p<0.01). Respiratory rate (RR) was significantly higher in CF compared to CG at QB and during PEP (QB: 36.3±7 vs. 28.9±5.1; P10: 33.8±14 vs. 30.6±17.6; P15: 37.5±16.6 vs. 22.5±8.3; P20: 37.8±14.1 vs. 22.5±8.3 min-1) (p <0.005). Minute ventilation was significantly higher during the use of PEP compared to QB in both groups (QB: 10.4±3.3 vs. 8.1±1.2; P10: 15.6±6.2 vs. 19.5±8.4; P15: 19.4±7.6 vs. 16±9.2; P20: 16.6±8.1 vs. 17.8±9.6 for CFG and CG, respectively; p<0.005).

![Figure][1] 



In conclusion, during PEP patients with CF show a more rapid and shallow breathing pattern, with higher respiratory rate and lower tidal volume compared to controls. This should be taken into account for an optimal setting of PEP level.

 [1]: pending:yes
R-spondins induce canonical Wnt signaling in lung epithelial cells
Authors: Wioletta Skronska-Wasek, Kathrin Mutze, Melanie Königshoff
Journal: European Respiratory Journal (2014)

Objective : Emphysema, one of the main features of chronic obstructive pulmonary disease (COPD), is characterized by destruction of the lung parenchyma and limited endogenous lung repair. Recently, Wnt/β-catenin signal activation has been shown to induce lung repair in experimental emphysema. Here, we aim to investigate the potential of the Wnt pathway agonist R-spondin (RSPO) to initiate lung repair.  Methods : To determine the influence of RSPO on Wnt/β-catenin signaling in lung epithelial cells and fibroblasts, we performed TOPflash luciferase assays, qPCR and Western blot.  Results:  We demonstrate that RSPO1 and 2 induced β-catenin dependent gene transcription in murine lung epithelial cells, but not in murine lung fibroblasts, as analyzed by luciferase activity. This suggests that lung epithelial cells have a different capability to respond to RSPO. To investigate the underlying mechanisms, we examined Wnt receptor expression and found Frizzled 4, 5, 7, 9 and 10, and Lgr5 co-receptor to be enriched in murine lung epithelial cells in comparison with murine lung fibroblasts. Interestingly, we observed that Lgr5 was down-regulated on protein level in COPD patients and on mRNA level in a murine model of experimental emphysema. Moreover, RSPO treatment induced alterations in Wnt receptor expression in lung epithelial cells and led to induction of alveolar epithelial markers expression.  Conclusions:  RSPOs potentiate Wnt/β-catenin signaling in the murine lung epithelial cells and alter the expression of Wnt receptors. Thus, RSPO treatment might contribute to the induction of lung repair processes.
Abstract 2825: A Large Chinese Family With Type-1 Short QT Syndrome
Authors: Yaxun Sun, Ping Zhang, Haicheng Zhang, Li Zhang, Jihong Guo
Journal: Circulation (2009)

Background: The short QT syndrome (SQTS), a newly recognized and extremely rare channelopathy, is featured by short QT interval associated with increased risks of sudden death (SD). Here, we report...
Wire-Guided Balloon Coloplasty – a New Treatment for Colorectal Strictures?
Authors: A K Banerjee, T K Walters, R Wilkins, M Burke
Journal: Journal of the Royal Society of Medicine (1991)

A new technique for dilatation of colorectal anastomotic strictures – wire-guided balloon coloplasty – is described. It is suitable for high strictures, may be performed without general anaesthetic and is repeatable. It does not require endoscopy and may be used to relieve obstructive symptoms in both benign and malignant strictures so avoiding the need for a defunctioning colostomy.
The Role of Matrix Metalloproteinases in Leukocyte Transmigration in Murine Experimental Autoimmune Encephalomyelitis
Authors: Smriti Agrawal
Journal: The Journal of Experimental Medicine (2006)

Murine experimental autoimmune encephalomyelitis (EAE) is a commonly used model in the investigation of the human disease multiple sclerosis (MS), a debilitating inflammatory disease of the central nervous system (CNS). MS and EAE involve multiple steps, primarily, auto-antigenic leukocyte (mainly T-cells and macrophages) crossing the blood-brain barrier and later their invasion into the CNS where they degrade myelin basic protein, eventually resulting in axonal degradation and CNS inflammation. Major MS/EAE research focuses their attention on the detrimental effects of leukocytes within the CNS and the role of proteases in these inflamed areas of the CNS. Our work, in contrast focuses mainly on the first step of leukocyte migration through the blood-brain barrier. This is the rate limiting step in both EAE and MS, without which clinical symptoms of the disease do not appear. In this study we demonstrates that the gelatinases, MMP-2 and MMP-9 are the major MMPs active in EAE and localize their activity in the CNS parenchyma subjacent to the parenchymal basement membrane/astroglial border, and we identify ?-dystroglycan to be a specific substrate for the active MMPs at the level of the blood-brain barrier. This is the first identification of a gelatinase substrate at the level of the blood-brain barrier. We further identify macrophages as the major source of MMP-2 and MMP-9, and demonstrate that elimination of both MMP-2 and MMP-9 (double KO mice, and treatment with specific inhibitors) protects mice against EAE. Our date further suggest that MMP-2 and MMP-9 not only have an effect at the BBB, but also at earlier stages of EAE induction. Finally, we examine the TNF-? KO mouse, which have a characteristic delay in EAE onset with prolonged retention of leukocytes in the perivascular cuff. (Less)