tbuckley/cabot-search huggingface dataset:
Correlation between confocal laser endomicroscopy of distal airways and pulmonary high resolution computed tomography features
Authors: Olesya Danilevskaya, Alexander Averyanov, Anna Sotnikova, Viktor Lesnyak, Dmitry Sazonov, Oleg Kuzovlev, Oleg Shablovsky
Journal: European Respiratory Journal (2013)

Probe-based confocal laser endomicroscopy (pCLE) is a new method of visualization of distal airways also known as alveoscopy.   Aim  to compare the pCLE images with HRCT data in corresponding lung segments.   Methods  HRCT scans were studied in 15 patients with pneumonia, 10 with pulmonary sarcoidosis, 7 with emphysema, 5 with adenocarcinoma and 3 with pulmonary alveolar proteinosis (PAP). The following radiologic signs were analyzed: low-density areas (LDA) and consolidation areas (CA), ground-glass opacity (GGO) and crazy paving (CP). pCLE images were assessed on following criteria: quantity of alveolar macrophages and floating intraalveolar substances, microvessels diameter, elastic fibers thickness.   Results  The most expressed correlations at LDA, CA and CP were with the amount of alveolar macrophages, floating substances, and thickness of elastic fibers.  GGO feature had correlations with the thickness of elastic fibers, and with the amount of floating substances.   Conclusion  Some pCLE signs have strong correlation with HRCT data. Alveoscopy can be used as additional diagnostic method of lung diseases.
Deep sequencing and SNP array analyses of pediatric T-cell acute lymphoblastic leukemia reveal NOTCH1 mutations in minor subclones and a high incidence of uniparental isodisomies affecting CDKN2A
Authors: Kristina Karrman, Anders Castor, Mikael Behrendtz, Erik Forestier, Linda Olsson, Mats Ehinger, Andrea Biloglav, Thoas Fioretos, Kajsa Paulsson, Bertil Johansson
Journal: Journal of Hematology & Oncology (2015)

Pediatric T-cell acute lymphoblastic leukemia (T-ALL) is a genetically heterogeneous disease that arises in a multistep fashion through acquisition of several genetic aberrations, subsequently giving rise to a malignant, clonal expansion of T-lymphoblasts. The aim of the present study was to identify additional as well as cooperative genetic events in T-ALL. A population-based pediatric T-ALL series comprising 47 cases was investigated by SNP array and deep sequencing analyses of 75 genes, in order to ascertain pathogenetically pertinent aberrations and to identify cooperative events. The majority (92%) of cases harbored copy number aberrations/uniparental isodisomies (UPIDs), with a median of three changes (range 0–11) per case. The genes recurrently deleted comprised CDKN2A, CDKN2B, LEF1, PTEN, RBI, and STIL. No case had a whole chromosome UPID; in fact, literature data show that this is a rare phenomenon in T-ALL. However, segmental UPIDs (sUPIDs) were seen in 42% of our cases, with most being sUPID9p that always were associated with homozygous CDKN2A deletions, with a heterozygous deletion occurring prior to the sUPID9p in all instances. Among the 75 genes sequenced, 14 (19%) were mutated in 28 (72%) of 39 analyzed cases. The genes targeted are involved in signaling transduction, epigenetic regulation, and transcription. In some cases, NOTCH1 mutations were seen in minor subclones and lost at relapse; thus, such mutations can be secondary events. Deep sequencing and SNP array analyses of T-ALL revealed lack of wUPIDs, a high proportion of sUPID9p targeting CDKN2A, NOTCH1 mutations in subclones, and recurrent mutations of genes involved in signaling transduction, epigenetic regulation, and transcription.
Elder siblings enhance the effect of filaggrin mutations on childhood eczema: Results from the 2 birth cohort studies LISAplus and GINIplus
Authors: Claudia Cramer, Elke Link, Maike Horster, Sibylle Koletzko, Carl-P. Bauer, Dietrich Berdel, Andrea von Berg, Irina Lehmann, Olf Herbarth, Michael Borte, Beate Schaaf, Heidrun Behrendt, Chih-Mei Chen, Stefanie Sausenthaler, Thomas Illig, H.-Erich Wichmann, Joachim Heinrich, Ursula Krämer
Journal: Journal of Allergy and Clinical Immunology (2010)
Inside Information: Financial Conflicts of Interest for Research Subjects in Early Phase Clinical Trials
Authors: P. R. Helft, M. J. Ratain, R. A. Epstein, M. Siegler
Journal: JNCI Journal of the National Cancer Institute (2004)

In recent years, several research subjects have told us that they had bought or intended to buy stock in the companies sponsoring the clinical trials in which they were enrolled. This situation has led us to ask what, if any, are physician-investigators' scientific, ethical, and legal responsibilities concerning research subjects who choose to buy stock in the companies sponsoring the clinical trials in which they are participating. Although the scope of this problem is unknown and is likely to be small, this commentary examines the scientific, ethical, and legal concerns raised by such activities on the part of research subjects enrolled in early phase clinical trials. In addition, this commentary also outlines the basis for our opinion that research subjects involved in an early phase clinical trial should avoid the financial conflicts of interest created by trading stock in the company sponsoring the clinical trial.
Pretargeted Dual-Modality Immuno-SPECT and Near-Infrared Fluorescence Imaging for Image-Guided Surgery of Prostate Cancer
Authors: Susanne Lütje, Mark Rijpkema, David M. Goldenberg, Catharina M. van Rij, Robert M. Sharkey, William J. McBride, Gerben M. Franssen, Cathelijne Frielink, Wijnand Helfrich, Wim J.G. Oyen, Otto C. Boerman
Journal: Cancer Research (2014)

Radical removal of malignant lesions may be improved using tumor-targeted dual-modality probes that contain both a radiotracer and a fluorescent label to allow for enhanced intraoperative delineation of tumor resection margins. Because pretargeting strategies yield high signal-to-background ratios, we evaluated the feasibility of a pretargeting strategy for intraoperative imaging in prostate cancer using an anti-TROP-2 x anti-HSG bispecific antibody (TF12) in conjunction with the dual-labeled diHSG peptide (RDC018) equipped with both a DOTA chelate for radiolabeling purposes and a fluorophore (IRdye800CW) to allow near-infrared optical imaging. Nude mice implanted s.c. with TROP-2-expressing PC3 human prostate tumor cells or with PC3 metastases in the scapular and suprarenal region were injected i.v. with 1 mg of TF12 and, after 16 hours of tumor accumulation and blood clearance, were subsequently injected with 10 MBq, 0.2 nmol/mouse of either (111)In-RDC018 or (111)In-IMP288 as a control. Two hours after injection, both microSPECT/CT and fluorescence images were acquired, both before and after resection of the tumor nodules. After image acquisition, the biodistribution of (111)In-RDC018 and (111)In-IMP288 was determined and tumors were analyzed immunohistochemically. The biodistribution of the dual-label RDC018 showed specific accumulation in the TROP-2-expressing PC3 tumors (12.4 ± 3.7% ID/g at 2 hours postinjection), comparable with (111)In-IMP288 (9.1 ± 2.8% ID/g at 2 hours postinjection). MicroSPECT/CT and near-infrared fluorescence (NIRF) imaging confirmed this TROP-2-specific uptake of the dual-label (111)In-RDC018 in both the s.c. and metastatic growing tumor model. In addition, PC3 metastases could be visualized preoperatively with SPECT/CT and could subsequently be resected by image-guided surgery using intraoperative NIRF imaging, showing the preclinical feasibility of pretargeted dual-modality imaging approach in prostate cancer.
Accessibility, acceptability, and effectiveness in primary care of routine telephone review of asthma: pragmatic, randomised controlled trial
Authors: H. Pinnock
Journal: BMJ (2003)

<h3>Abstract</h3> <b>Objective:</b> To determine whether routine review by telephone of patients with asthma improves access and is a good alternative to face to face reviews in general practices. <b>Design:</b> Pragmatic, randomised controlled trial. <b>Setting:</b> Four general practices in England. <b>Participants:</b> 278 adults who had not been reviewed in the previous 11 months. <b>Intervention:</b> Participants were randomised to either telephone review or face to face consultation with the asthma nurse. <b>Main outcome measures:</b> Primary outcome measures were the proportion of participants who were reviewed within three months of randomisation and disease specific quality of life, as measured by the Juniper mini asthma quality of life questionnaire. Secondary outcome measures included the validated "short Q" asthma morbidity score, nursing care satisfaction questionnaire score, and length of consultation. <b>Results:</b> Of 137 people randomised to telephone consultation, 101 (74%) were reviewed, compared with 68 reviewed (48%) of the 141 people in the surgery group, a difference of 26% (95% confidence interval 14% to 37%; P&lt;0.001; number needed to treat 3.8). Three months after randomisation the two groups did not differ in the Juniper score (risk difference −0.07 (95% confidence interval −0.40 to 0.27) or in satisfaction with the consultation (risk difference −0.07 (−0.27 to 0.13)). Telephone consultations were on average 10 minutes shorter than reviews held in the surgery (mean difference 10.7 minutes (12.6 to 8.8; P&lt;0.001)). <b>Conclusions:</b> Compared with face to face consultations in the surgery, telephone consultations enable more people with asthma to be reviewed, without clinical disadvantage or loss of satisfaction. A shorter duration means that telephone consultations are likely to be an efficient option in primary care for routine review of asthma. <h3>What is already known on the topic</h3> Regular review of patients with asthma reduces morbidity and is endorsed as good practice by UK and international guidelines, but only about a third of patients attend for their annual review Most studies of telephone consultation in primary care have focused on consultations requested by patients rather than their use in the routine review of chronic disease <h3>What this study adds</h3> Telephone consultations enable more people with asthma to be reviewed Telephone consultations are shorter than face to face consultations, without any apparent clinical disadvantage Patients are satisfied with telephone consultations
Clinical application of a rapid lung-orientated immunoassay in individuals with possible tuberculosis
Authors: R A M Breen, S M Barry, C J Smith, R J Shorten, J P Dilworth, I Cropley, T D McHugh, S H Gillespie, G Janossy, M C I Lipman
Journal: Thorax (2007)

<h3>Background:</h3> Immunological ex vivo assays to diagnose tuberculosis (TB) have great potential but have largely been blood-based and poorly evaluated in active TB. Lung sampling enables combined microbiological and immunological testing and uses higher frequency antigen-specific responses than in blood. <h3>Methods:</h3> A prospective evaluation was undertaken of a flow cytometric assay measuring the percentage of interferon-γ synthetic CD4+ lymphocytes following stimulation with purified protein derivative of <i>Mycobacterium tuberculosis</i> (PPD) in bronchoalveolar lavage fluid from 250 sputum smear-negative individuals with possible TB. A positive assay was defined as &gt;1.5%. <h3>Results:</h3> Of those who underwent lavage and were diagnosed with active TB, 95% (106/111) had a positive immunoassay (95% CI 89% to 98%). In 139 individuals deemed not to have active TB, 105 (76%) were immunoassay negative (95% CI 68% to 82%). Of the remaining 24% (34 cases) with a positive immunoassay, a substantial proportion had evidence of untreated TB; in two of these active TB was subsequently diagnosed. Assay performance was unaffected by HIV status, disease site or BCG vaccination. In culture-positive pulmonary cases, response to PPD was more sensitive than nucleic acid amplification testing (94% vs 73%). The use of early secretory antigen target-6 (ESAT-6) responses in 71 subjects was no better than PPD, and 19% of those with culture-confirmed TB and a positive PPD immunoassay had no detectable response to ESAT-6. <h3>Conclusions:</h3> These findings suggest that lung-orientated immunological investigation is a potentially powerful tool in diagnosing individuals with sputum smear-negative active TB, regardless of HIV serostatus.
Relationship Between Number of Ovulatory Cycles and Accumulation of Mutant p53 in Epithelial Ovarian Cancer
Authors: P. M. Webb, D. M. Purdie, M. C. Cummings, M. D. Walsh, A. Green, G. Chenevix-Trench
Journal: JNCI Journal of the National Cancer Institute (1998)

It has been suggested that increased numbers of ovulations might increase the risk of p53 gene (also known as TP53) mutation in the ovarian epithelium, thereby leading to the development of cancer. The data supporting this hypothesis have come from an observation that accumulation of p53 protein in epithelial ovarian cancer was strongly associated with increasing numbers of ovulatory cycles. We have further investigated the association between ovulatory history and p53 gene mutation by use of data from a large case-control study of ovarian cancer in Australia.Tissue blocks were available for immunohistochemical analysis of p53 protein from 234 case subjects, aged 18-79 years, who had invasive epithelial ovarian cancer. Epidemiologic data were also available for these women and for 855 control subjects. Case-case comparisons were made by use of prevalence ratios and 95% confidence intervals (CIs), and case-control comparisons were made by use of odds ratios (ORs) and 95% CIs. All statistical tests were two-sided.There was no association between p53 accumulation and years of ovulation. Women with p53-positive cancers had undergone an average of 29.3 years of ovulation compared with 29.0 years of ovulation for women with p53-negative cancers (P=.8). Although the overall risk of ovarian cancer development was significantly increased in women who had undergone more years of ovulation (OR=2.17; 95% CI =1.54-3.05-for > or =35 years versus <23 years of ovulation), there was no difference in the risk associated with p53-positive and p53-negative cancers.These results confirm the association between increased ovulation and ovarian cancer risk but do not support the hypothesis that this association is due to an increased risk of p53 mutation with a greater number of ovulatory cycles.
Enigma homolog 1 scaffolds protein kinase D1 to regulate the activity of the cardiac L-type voltage-gated calcium channel
Authors: Andrés D. Maturana, Sébastien Wälchli, Miki Iwata, Stephan Ryser, Johannes Van Lint, Masahiko Hoshijima, Werner Schlegel, Yasuhiro Ikeda, Katsuyuki Tanizawa, Shun'ichi Kuroda
Journal: Cardiovascular Research (2008)

AimsIn cardiomyocytes, protein kinase D1 (PKD1) plays a central role in the response to stress signals. From a yeast two-hybrid assay, we have identified Enigma Homolog 1 (ENH1) as a new binding partner of PKD1. Since in neurons, ENH1, associated with protein kinase Cε, was shown to modulate the activity of N-type calcium channels, and the pore-forming subunit of the cardiac L-type voltage-gated calcium channel, α1C, possesses a potential phosphorylation site for PKD1, we studied here a possible role of ENH1 and PKD1 in the regulation of the cardiac L-type voltage-gated calcium channel.
Fc Optimization of Therapeutic Antibodies Enhances Their Ability to Kill Tumor Cells<i>In vitro</i>and Controls Tumor Expansion<i>In vivo</i>via Low-Affinity Activating Fcγ Receptors
Authors: Jeffrey B. Stavenhagen, Sergey Gorlatov, Nadine Tuaillon, Christopher T. Rankin, Hua Li, Stephen Burke, Ling Huang, Syd Johnson, Ezio Bonvini, Scott Koenig
Journal: Cancer Research (2007)

Abstract Monoclonal antibodies (mAb) are widely used in the treatment of non-Hodgkin's lymphoma and autoimmune diseases. Although the mechanism of action in vivo is not always known, the therapeutic activity of several approved mAbs depends on the binding of the Fcγ regions to low-affinity Fcγ receptors (FcγR) expressed on effector cells. We did functional genetic screens to identify IgG1 Fc domains with improved binding to the low-affinity activating Fc receptor CD16A (FcγRIIIA) and reduced binding to the low-affinity inhibitory Fc receptor, CD32B (FcγRIIB). Identification of new amino acid residues important for FcγR binding guided the construction of an Fc domain that showed a dramatically enhanced CD16A binding and greater than a 100-fold improvement in antibody-dependent cell-mediated cytotoxicity. In a xenograft murine model of B-cell malignancy, the greatest enhancement of an Fc-optimized anti-human B-cell mAb was accounted for by improved binding to FcγRIV, a unique mouse activating FcγR that is expressed by monocytes and macrophages but not natural killer (NK) cells, consistent with experimental and clinical data suggesting that mononuclear phagocytes, effector cells expressing both activating and inhibitory FcγR, are critical mediators of B-cell depletion in vivo. By using mice transgenic for human CD16A, enhanced survival was observed due to expression of CD16A-158phe on monocytes and macrophages as well as on NK cells in these mice. The design of new generations of improved antibodies for immunotherapy should aim at Fc optimization to increase the engagement of activating FcγR present on the surface of tumor-infiltrating effector cell populations. [Cancer Res 2007;67(18):8882–90]
Extending the benefits of breast cancer screening
Authors: U. Werneke, K. McPherson
Journal: BMJ (1998)

Papers pp 376, 388

Ever since the implementation of the NHS breast screening programme in 1988 two important questions have been consistently raised. Should the age range of women invited be extended from the current range of 50-64 years, and should the screening interval be reduced from the current three years? If we are to believe the cost effectiveness analysis by Boer et al in this week's issue (p 376),1 an increase in age to 69 and a two year interval would each generate substantial benefits in life years saved and deaths averted—but, needless to say, at a substantial cost. Moreover, the authors'conclusion that extending the age range is expected to prevent more deaths, whereas shortening the screening interval would save more life years leaves policymakers with a—not unfamiliar—ethical dilemma.

It is obviously desirable to improve life expectancy in those women already eligible for screening. Reducing the interval cancer rate, which is particularly high in the third year of …
THetA: inferring intra-tumor heterogeneity from high-throughput DNA sequencing data
Authors: Layla Oesper, Ahmad Mahmoody, Benjamin J Raphael
Journal: Genome biology (2013)

Tumor samples are typically heterogeneous, containing admixture by normal, non-cancerous cells and one or more subpopulations of cancerous cells. Whole-genome sequencing of a tumor sample yields reads from this mixture, but does not directly reveal the cell of origin for each read. We introduce THetA (Tumor Heterogeneity Analysis), an algorithm that infers the most likely collection of genomes and their proportions in a sample, for the case where copy number aberrations distinguish subpopulations. THetA successfully estimates normal admixture and recovers clonal and subclonal copy number aberrations in real and simulated sequencing data. THetA is available at http://compbio.cs.brown.edu/software/.
Surgery of the stomach, duodenum and small intestine
Authors: C G Clark
Journal: Gut (1988)

Crohn's or poisoning?SIR,-Recent work by Bjarnason et al' on blood and protein loss through small intestinal inflammation induced by non-steroidal anti-inflammatory drugs (NSAIDs) would appear to have potential medico- legal implications on the result of a celebrated murder trial which took place in 1859.A certain Dr Smethurst was found by jury trial to have murdered his wife by administration of an unknown poison.The Home Secretary, however, taking the advice of Sir Benjamin Brodie, Surgeon to St George's Hospital, granted Dr Smethurst a free pardon since there was not 'absolute and complete evidence of his guilt'.2The necropsy findings have suggested subsequently that his wife had Crohn's disease.'In the small intestine 'nothing remarkable was observed until the lower end of the ileum was reached, when at about three feet from its termination in the caecum, the mucous membrane commenced to exhibit an inflammatory response'.In the caecum 'inflammation of the most acute and violent character was observed . . . the bare muscular coat was seen beneath.The muscular coat itself in the caecum was likewise infiltrated with this exudation . . .and there is no doubt that through this part of the intestine some transudation had occurred which had set up the peritonitis.No actual perforation was discoverable.'4 These findings could also be explained by severe NSAID induced ileitis.Salicylic acids are present in large concentrations in oil of wintergreen and admin- istration of such medication, which was in common use at the time, may have resulted in the first reported case of non-steroidal drug induced intestinal inflam- mation in man.
Role of Sodium-Calcium Exchanger in Modulating the Action Potential of Ventricular Myocytes From Normal and Failing Hearts
Authors: Antonis A. Armoundas, Ion A. Hobai, Gordon F. Tomaselli, Raimond L. Winslow, Brian O’Rourke
Journal: Circulation Research (2003)

Increased Na + -Ca 2+ exchange (NCX) activity in heart failure and hypertrophy may compensate for depressed sarcoplasmic reticular Ca 2+ uptake, provide inotropic support through reverse-mode Ca 2+ entry, and/or deplete intracellular Ca 2+ stores. NCX is electrogenic and depends on Na + and Ca 2+ transmembrane gradients, making it difficult to predict its effect on the action potential (AP). Here, we examine the effect of [Na + ] i on the AP in myocytes from normal and pacing-induced failing canine hearts and estimate the direction of the NCX driving force using simultaneously recorded APs and Ca 2+ transients. AP duration shortened with increasing [Na + ] i and was correlated with a shift in the reversal point of the NCX driving force. At [Na + ] i ≥10 mmol/L, outward NCX current during the plateau facilitated repolarization, whereas at 5 mmol/L [Na + ] i , NCX had a depolarizing effect, confirmed by partially inhibiting NCX with exchange inhibitory peptide. Exchange inhibitory peptide shortened the AP duration at 5 mmol/L [Na + ] i and prolonged it at [Na + ] i ≥10 mmol/L. With K + currents blocked, total membrane current was outward during the late plateau of an AP clamp at 10 mmol/L [Na + ] i and became inward close to the predicted reversal point for the NCX driving force. The results were reproduced using a computer model. These results indicate that NCX plays an important role in shaping the AP of the canine myocyte, helping it to repolarize at high [Na + ] i , especially in the failing heart, but contributing a depolarizing, potentially arrhythmogenic, influence at low [Na + ] i .
Pancreatitis and lipase. A reevaluation with a five-minute turbidimetric lipase determination
Authors: L. J. Lifton
Journal: JAMA (1974)

Lipase activity was simultaneously determined with amylase activity in the sera of 30 hospitalized patients with acute pancreatitis. On admission to the study, 70% of patients with acute pancreatitis had increased serum amylase, 63% had increased lipase, and 83% had increased lipase, increased amylase, or both. All patients had either lipase or amylase increase at some time during the course of their disease. Lipase level elevation paralleled the amylase in the majority of cases. There were several instances of earlier elevation of the lipase level. The traditional thesis that lipase level elevation occurs later and lasts longer than that of amylase was not confirmed. Measurement of serum amylase and lipase levels together will improve diagnostic accuracy in acute pancreatitis. (<i>JAMA</i>229:47-50, 1974)