tbuckley/cabot-search huggingface dataset:
Chemoablation of melanoma with intralesional rose bengal (PV-10)
Authors: S. S. Agarwala, J. Thompson, M. Smithers, M. Ross, B. Coventry, D. Minor, C. Scoggins, P. Hersey, E. Wachter
Journal: Journal of Clinical Oncology (2009)

9060 Background: Intralesional rose bengal (PV-10, a sterile 10% solution in saline) can elicit selective ablation of solid tumors and an apparent bystander response in untreated lesions. In phase 1 testing in 20 subjects with AJCC Stage III (19 subjects) or IV (1 subject) melanoma, a single injection of PV-10 into 1–20 lesions led to durable objective response (OR) at 12–24 weeks in 40% of subjects (20% CR + 20% PR by modified RECIST) and locoregional disease control (CR + PR + SD) in 75% of subjects. Untreated bystander lesions achieved an OR in 15% of subjects, and all subjects with an OR of their injected lesions achieved disease control of their bystander lesions. PV-10 was well tolerated, with only one Grade 3 adverse event (photosensitivity reaction). The most common AEs were transient pain at the treatment site (75% of subjects), followed by local inflammation or infection (25%). Methods: Expanded phase 2 testing commenced in late 2007 in up to 80 subjects with measurable Stage III or IV melanoma. After an initial treatment of 1–20 cutaneous, subcutaneous or nodal lesions, new or incompletely responsive lesions can be retreated at weeks 8, 12 or 16, with follow-up to 52 weeks. An additional 1–2 lesions, including visceral lesions, remain untreated for assessment of bystander response. Seven centers in Australia and the USA are enrolling subjects, with completion of enrolment expected by mid-2009. A modified Fleming design allows interim assessment of safety and OR at weeks 4 and 24, respectively, after treatment of the 20 th and 40 th subjects. The primary end-point is OR of injected lesions in the intent-to-treat population; secondary endpoints include OR of bystander lesions and PFS. Results: Interim safety data for the first 40 subjects treated is comparable to phase 1, with transient mild to moderate locoregional pain, vesicles or edema most common; Grade 3 AEs have been rare (1 case each of vesicles and skin flap necrosis), with no Grade 4 or 5 AEs attributed to PV-10. Interim efficacy for the first 20 subjects is also comparable to that of phase 1 (15% CR + 15% PR); efficacy data for the first 40 subjects will be presented at the meeting. Conclusions: The safety and efficacy profile of intralesional therapy with PV-10 compares favorably with available therapeutic options for this patient population. No significant financial relationships to disclose.
Detecting Genomic Signatures of Natural Selection with Principal Component Analysis: Application to the 1000 Genomes Data
Authors: Nicolas Duforet-Frebourg, Keurcien Luu, Guillaume Laval, Eric Bazin, Michael G.B. Blum
Journal: Molecular Biology and Evolution (2015)

To characterize natural selection, various analytical methods for detecting candidate genomic regions have been developed. We propose to perform genome-wide scans of natural selection using principal component analysis (PCA). We show that the common FST index of genetic differentiation between populations can be viewed as the proportion of variance explained by the principal components. Considering the correlations between genetic variants and each principal component provides a conceptual framework to detect genetic variants involved in local adaptation without any prior definition of populations. To validate the PCA-based approach, we consider the 1000 Genomes data (phase 1) considering 850 individuals coming from Africa, Asia, and Europe. The number of genetic variants is of the order of 36 millions obtained with a low-coverage sequencing depth (3×). The correlations between genetic variation and each principal component provide well-known targets for positive selection (EDAR, SLC24A5, SLC45A2, DARC), and also new candidate genes (APPBPP2, TP1A1, RTTN, KCNMA, MYO5C) and noncoding RNAs. In addition to identifying genes involved in biological adaptation, we identify two biological pathways involved in polygenic adaptation that are related to the innate immune system (beta defensins) and to lipid metabolism (fatty acid omega oxidation). An additional analysis of European data shows that a genome scan based on PCA retrieves classical examples of local adaptation even when there are no well-defined populations. PCA-based statistics, implemented in the PCAdapt R package and the PCAdapt fast open-source software, retrieve well-known signals of human adaptation, which is encouraging for future whole-genome sequencing project, especially when defining populations is difficult.
Effects of anaerobiosis upon morphology and energy metabolism of alveolar macrophages cultured in gas phase
Authors: M Cazin, D Paluszezak, A Bianchi, JC Cazin, C Aerts, C Voisin
Journal: European Respiratory Journal (1990)

Metabolic and morphological effects of anoxia were studied in alveolar macrophages obtained by lung lavage from guinea-pigs by means of an original method of cell culture allowing direct contact with air without interposition of liquid medium. After selection by glass adherence, alveolar cells were layered on a porous membrane applied to the surface of a reservoir filled with nutrient medium. Alveolar macrophages were then cultured in gas phase under either aerobic or anaerobic conditions for 24, 48 and 72 h. Cellular adenosine triphosphate (ATP) content, an indicator of cell vitality, significantly decreased by 68 and 88% after 48 and 72 h of exposure to anaerobic environment, respectively. Significant increases in lactate production (68% at 24 h) and in glucose uptake (125% at 24 h), evidence of marked glycolytic activity, occurred before these falls in intracellular ATP and parallel decreases in culture medium pyruvate level (76 and 85% at 48 and 72 h, respectively). The shift of energy metabolism resulted in cell death after 72 h, as noted by morphological degeneration and decreased cellular ATP content. Twenty-four hour re-exposure to normoxic atmosphere showed that recovery was possible when duration of anaerobiosis did not exceed 48 h. This reversibility in anoxic cell injury has been related to plasma membrane integrity. The results of these studies indicate that alveolar macrophage resistance to anaerobiosis is limited as ATP content falls and morphological degeneration occurs after 48 h. This novel approach of anaerobic effects at the cell level should be adaptable to investigations of activity and, in particular, the mechanisms of metabolic activity of antianoxic drugs.
Increased incidence of Merkel cell polyoma virus in non-small-cell lung cancer
Authors: Katerina Antoniou, Ismini Lasithiotaki, Stavros Derdas, Emmanuela Sarchianaki, Anna Psaraki, Demetrios Spandidos, Eustathios Stathopoulos, Nikolaos Siafakas, George Sourvinos
Journal: European Respiratory Journal (2012)

Introduction and aim of the study: Polyoma viruses such as BK virus (BKV), JC virus (JCV) and Merkel Cell Polyoma virus (McPyV) are typically non-oncogenic. The evidence for their role in human cancer remains controversial although they have been detected in a variety of human neoplasms. The aim of this study is to determine the incidence of the most common polyoma viruses in adults McPyV, BKV and JCV in a large non-small cell lung cancer (NSCLC) patient population.

Methods: Real Time PCR and nested PCR were employed to assess the presence of BKV, MCPyV and JCV DNA in tissue biopsies from 100 patients with primary NSCLC as well as lung tissue specimens from macroscopically healthy sites of their lung.

Results: BKV and JCV DNA were not detected in lung tissues biopsies or control specimens. However, ten specimens from lung cancer tissue were found positive for the presence of MCPyV DNA (10/100, 10%), whereas no control sample was tested positive for the virus. The MCPyV positive samples were obtained from male patients in 90% (9/10) of the cases, with a mean age of 64 years and the following histological types: adenocarcinoma 5/10 cases (50%), squamous cell carcinoma 3/10 cases (30%), bronchoalveolar carcinoma 1/10 cases (10%) and undifferentiated large cell lung carcinoma 1/10 cases (10%).

Conclusion: The detected MCPyV prevalence in NSCLC may suggest a pathogenetic role of this virus in NSCLC of the lung. These results may implicate MCPyV mainly with lung adenocarcinoma, while providing evidence of the potential oncogenic role of this virus in NSCLC.
Clinical application of genomic profiling in breast cancer and the TAILORx trial
Authors: Joseph A. Sparano
Journal: Clinical Cancer Research (2010)

Abstract Breast cancer is characterized by clinical and molecular heterogeneity. Microarray-based gene expression has identified distinct expression profiles associated differing prognosis and response to therapy. Newer technologies now permit evaluation not only of gene expression, but also single nucleotide polymorphisms, gene copy number, genomic mutations, and epigenomic or microRNA patterns that modulate gene expression. These state-of-the-art molecular approaches offer new insights into the pathogenesis of breast cancers, and offer the promise to improve the prevention, diagnosis, and management of the disease. Although many gene expression assays have been shown to provide prognostic information that is complementary to classical clinicopathologic features, the clinical utility of such assays is uncertain — that is, how do the results alter patient care, and do patients benefit from that change? Most attention has focused on using these assays to reduce overtreatment in patients with estrogen-receptor positive, lymph node negative breast cancer, which accounts for about one-half of all breast cancers, and about 8% of all cancers in the United States. Evidence suggest that some assays do have clinical utility when used appropriately, usually by reducing overtreatment with chemotherapy in patients who may otherwise have an excellent prognosis with local therapy plus endocrine therapy alone — or “treatment sparing”. Other potential examples of clinical utility include “treatment selection” (selecting individuals for chemotherapy when standard clinicopathologic features would have suggested otherwise) and “treatment direction” (selecting individuals for chemotherapy when clinicopathologic features suggested therapeutic equipoise). There are three breast cancer clinical trials which have integrated multiparameter assays into the clinical decision making, including the TAILORx and CHORUS trials (which use the 21 gene assay) and the MINDACT trial (which uses the 70 gene assay). The results of these trials will inform us regarding the clinical utility of these assays, and provide a valuable resource for evaluating other clinical cancer tests in the future.
Prognostic Value of <i>p53</i> Genetic Changes in Colorectal Cancer
Authors: Ulf Kressner, Mats Inganäs, Sara Byding, Ingrid Blikstad, Lars Påhlman, Bengt Glimelius, Gudrun Lindmark
Journal: Journal of Clinical Oncology (1999)

PURPOSE: To explore whether there is a linkage between different mutations in the p53 gene in primary colorectal cancer and the risk of death from colorectal cancer in a large group of patients with long follow-up. We also compared a complementary DNA-based sequencing method and an immunohistochemical (IHC) method for detecting p53 protein overexpression in colorectal cancer. MATERIALS AND METHODS: The entire coding region of the p53 gene was sequenced in 191 frozen tumor samples collected from January 1988 to November 1992. RNA was extracted and synthesized to cDNA. p53 was amplified by the polymerase chain reaction, and the DO-7 monoclonal antibody was used in the IHC assessments. RESULTS: Mutations were detected in 99 samples (52%) from 189 patients. There was a significant relationship between the p53 mutational status and the cancer-specific survival time, with shorter survival time for patients who had p53 mutations than for those who did not (P = .01, log-rank test). Mutations outside the evolutionarily conserved regions were associated with the worst prognosis. Multivariate analysis showed that the presence of p53 mutations was an independent prognostic factor (relative hazard, 1.7, P = .03). There was no significant relationship between overexpression of p53 protein, as determined by IHC analysis, and cancer-specific survival. CONCLUSION: Mutational analyses of the p53 gene, using cDNA sequencing in colorectal cancer, provide useful prognostic information. In addition, cDNA sequencing gives better prognostic information than IHC assessment of p53 protein overexpression.
Doctor-Patient Communication in Surgery
Authors: Jessica Richards, Peter McDonald
Journal: Journal of the Royal Society of Medicine (1985)

The efficiency of communication between junior hospital doctors and 77 general surgical patients was assessed by using standardized questionnaires before and after the doctor/patient interview on both the patient and the house doctor. Patients were better informed about their illness than their surgery, and doctors wrongly estimated patients' knowledge in 41% of cases. Self-reported preoperative anxiety of patients was low and was estimated wrongly by house doctors in 58% of cases. In 52% of cases house doctors were considered by patients to be the most important source of information, but patients had little comprehension of the seniority of other doctors. Although 60% of patients were satisfied with the communication, the majority complained of lack of information concerning convalescence, postoperative pain and routine ward procedures.
Bladder Muscle Biopsy and Urethral Sphincter EMG in Patients with Bladder Dysfunction after Pelvic Surgery
Authors: R S Kirby, C J Fowler, S A Gilpin J A Gosling, E J G Milroy, R T Turner-Warwick
Journal: Journal of the Royal Society of Medicine (1986)

Eleven patients who suffered persistent bladder dysfunction after pelvic surgery have been investigated by needle urethral sphincter electromyography (EMG) and bladder muscle biopsy, and the results compared with those obtained in a series of controls. Individual motor units recorded from the urethral sphincter in patients who had undergone pelvic surgery were strikingly abnormal, suggesting the presence of reinnervation, and the density of detrusor innervation was significantly reduced. However, since reduction in the density of detrusor innervation may occur in circumstances other than peripheral nerve injury, we conclude that urethral sphincter EMG provides the most effective means of assessing damage to vesico-urethral innervation as a result of previous pelvic surgery.
Lung function following preterm premature rupture of membranes (PPROM)
Authors: Emma Satrell, Benedikte Lea, Ola Røksund, Maria Vollsæter, Hege Clemm, Hallvard Reigstad, Thomas Halvorsen
Journal: European Respiratory Journal (2014)

Introduction: Preterm premature rupture of membranes (PPROM) is an uncommon complication of pregnancy and is associated with neonatal lung disease and high mortality. Long-term pulmonary consequences are unknown.  Aim: To assess lung function in children born after pregnancies complicated by PPROM.  Methods: Lung function was examined in children born at Haukeland University Hospital in Norway during 1999-2005 with PPROM before 20 weeks9 gestation and of at least 2 weeks9 duration, and in controls born after a pregnancy with intact membranes and matched for gestational age (GA) and postnatal age.  Results: Of 18 PPROM infants, 5 died and 11/13 survivors were examined. Mean (range) GA and weight at birth were 28.0 (25-32) vs. 28.8 (25-33) weeks and 1194 (680-1694) vs. 1238 (650-1830) grams for the PPROM vs. control group, and mean (range) age at examination was 10.3 (7.5-13.3) vs. 10.4 (7.9-13.3) years. There were no significant differences in any of the variables listed in the Table.  Conclusion: Lung function in childhood of survivors of pregnancies complicated by PPROM was similar to that of controls born at the same GA.
Adaptation of prevotella during acute infectious pulmonary exacerbation
Authors: Stuart Elborn, Denver Mooney, Michael Tunney, Stephanie McGrath, Leanne McIlreavey, Elinor Johnston, Thomas Matier
Journal: European Respiratory Journal (2014)

Introduction:   Prevotella  species are the predominant anaerobes detected in sputum samples from CF patients. Little is known about how these organisms survive interaction with the influx of immune components that occurs during pulmonary inflammation. Therefore, this study aimed to determine if the resistance of these organisms to the bactericidal activities of neutrophils and/or the complement system increased during CF pulmonary exacerbation   Methods:   Prevotella  isolates, highly similar by PFGE, were cultured from 2 CF patients prior to and immediately after antibiotic treatment of an infective pulmonary exacerbation. The 4 isolates were incubated with pooled human serum (t=60 mins), which contains complement, and with human neutrophils (t=20 mins). Decreases in bacterial cell viability were calculated relative to controls performed in the absence of the respective immune components   Results:   Post exacerbation isolates were significantly more resistant to the bactericidal effects of human serum (P    Conclusion:  Resistance of  Prevotella  species to complement mediated immune clearance increases during pulmonary exacerbation. Up-regulation of this key virulence determinant may reflect adaptation to prolonged exposure to complement during pulmonary exacerbation.
Mammary Tumor Virus Potentiation of Endogenous Prolactin Effect on Mammary Gland Differentiation
Authors: Menashe Ben-David, Walter E. Heston, David Rodbard
Journal: JNCI Journal of the National Cancer Institute (1969)

Mammary growth and differentiation were evaluated histologically in several inbred strains of virgin female mice with or without mammary tumor virus (MTV). The response to estradiol alone, perphenazine (a prolactin releaser) alone, and estradiol plus perphenazine, and the interaction of these treatments with the presence of MTV and genetic factors were evaluated in a multifactorial experiment. Statistical analysis and interpretation of the data were facilitated by use of Ridit analysis. Estradiol priming alone induced a significant degree of mammotropic response for nearly all treatment categories, but the responsiveness to estradiol varied significantly among the several strains. The presence or absence of MTV or of perphenazine did not change the estradiol effect. All strains of virus-free mice, with or without estradiol priming, showed an increase in the mammotropic index in response to perphenazine treatment. This perphenazine effect was significantly potentiated by MTV, whether the virus had been present since neonatal foster nursing, or whether it was injected concurrently with perphenazine. It is concluded that the MTV potentiates the mammotropic effect of endogenous prolactin released by perphenazine.
LSC 2013 abstract - Serum YKL-40 is increased in children with bronchopulmonary dysplasia compared to children with asthma
Authors: Anna James, Jon Konradsen, Björn Nordlund, Christina Ebersjö, Eva Berggren Boström, Ewa Henckel, Sven-Erik Dahlén, Gunilla Hedlin
Journal: European Respiratory Journal (2013)

Introduction:  Bronchopulmonary dysplasia (BPD) caused by prematurity is associated with more remodeling and fibrosis than asthma, yet symptoms and treatment of these two disorders are similar. The chitinase-like protein YKL-40, is a novel biomarker of asthma although the mechanisms involved are unknown. YKL-40 levels correlate with airway remodeling (Chupp et al. NEJM 2007) and YKL-40 increases smooth muscle proliferation (Bara et al. AJRCCM 2012). We aimed to compare serum YKL-40 in children with asthma and BPD.   Methods:  Age- and sex-matched children with diagnosed asthma (n=27) or BPD (n=28) were included in the study at 10 yrs of age. Serum YKL-40 levels were measured by ELISA.   Results:  YKL-40 was higher in children with BPD compared to asthma, fig 1, whereas FEV1 (%pred) was reduced in BPD (77.1 vs 84.1, p=0.03). Patients with high YKL-40 (upper quartile mean 17.5 ng/ml) had a lower FEV1 than those with low YKL-40 (lower quartile mean 11.5 ng/ml), (73% vs 85%, p 1 month than those with CPAP treatment for    Conclusion:  Serum YKL-40 levels are increased in BPD and relate to lung function and BPD severity suggesting that YKL-40 may be involved in airway remodeling and fibrosis.
Safety of Trastuzumab and Pertuzumab for Patients with Previously Treated Her2 Positive Advanced Breast Cancer
Authors: Haruna Sakaguchi, Mikiya Ishihara, Akihiko Sawaki, Keiki Nagaharu, Hiroyasu Oda, Yumiko Sugawara, Satoshi Tamaru, Yoshiki Yamashita, Toshiro Mizuno, Naoyuki Katayama
Journal: Annals of Oncology (2014)
Cardiovascular events related to the use of varenicline
Authors: Agustín S. Valido Morales, Patricia Guerrero Zamora, Ana Gomez Bastero Fernandez, Concepción Romero Muñoz, Andrés H. Vega Arias, Virginia Almadana Pacheo, Teodoro Montemayor Rubio
Journal: European Respiratory Journal (2012)

Lately, the FDA warned that varenicline may increase the risk of myocardial infarction or other cardiovascular events,being higher in patients with prior history.  Objective: To determine an increase in the number of cardiovascular events in a group of patients treated with varenicline vs bupropion.  Material and Methods:  Prospective study with the patients attending our smoking cessation practice in the last 6 months.We analyzed different variables and Cardiovascular events.  This evalution was carried out 3 and 6 months after the treatment initiation which lasted up to 2 months.We carried out a descriptive analysis.  Results:  From a total of 313 patients(175 varenicline;138 bupropion).The treatment with varenicline was more frequent in men who were older, with a main smoking history, diabetes, ischemic heart disease and higher scores in the Richmond test.We observed no significant differences regarding the cardiovascular events in both groups.  Conclusions:  Both drugs have shown the same safety profile for cardiovascular events.  We observed a higher frequency regarding the blood pressure increase.
Prevalence of undiagnosed psoriatic arthritis among psoriasis patients: Systematic review and meta-analysis
Authors: Axel Patrice Villani, Marie Rouzaud, Morgane Sevrain, Thomas Barnetche, Carle Paul, Marie-Aleth Richard, Marie Beylot-Barry, Laurent Misery, Pascal Joly, Michel Le Maitre, Selim Aractingi, François Aubin, Alain Cantagrel, Jean-Paul Ortonne, Denis Jullien
Journal: Journal of the American Academy of Dermatology (2015)