tbuckley/cabot-search huggingface dataset:
The Composition of the B Cell Receptor Repertoire In 7428 Cases of Chronic Lymphocytic Leukemia: One Third Stereotyped, Two Thirds Heterogeneous - What Does This Mean?
Authors: Andreas Agathaggelidis, Nikos Darzentas, Anastasia Hadzidimitriou, Xavier Brochet, Fiona Murray, Xiao-Jie Yan, Zadie Davis, Ellen van Gastel, Cristina Tresoldi, Charles C Chu, Nicola Cahill, Veronique Giudicelli, Boris Tichy, Lone Bredo Pedersen, Letizia Foroni, Paola Francia di Celle, Agnieszka Janus, Karin Smedby, Achilles Anagnostopoulos, Helene Merle-Beral, Nikolaos Laoutaris, Gunnar Juliusson, Sarka Pospisilova, Jesper Jurlander, Athanasios Tsaftaris, Marie-Paule Lefranc, Anton W. Langerak, David Graham Oscier, Nicholas Chiorazzi, Chrysoula Belessi, Frederic Davi, Richard Rosenquist, Paolo Ghia, Kostas Stamatopoulos
Journal: Blood (2010)
Abstract 11815: Prolonged Space Flight Induced Alterations in the Structure of Medaka Cardiac Muscle and Gene Expression
Authors: Hirokazu Enomoto, Nishant Mittal, Shinji Makino, Keiichi Fukuda
Journal: Circulation (2015)

Introduction: Cardiovascular deconditioning (reduction of ventricular mass and blood pressure) induced by prolonged spaceflight. Little has been reported about histology and gene expression pattern of heart after long time in the international space station (ISS). The purpose of this study is to examine how microgravity affects the structure and gene expression of medaka cardiac muscle. Methods: Fifteen medaka fishes were sent to ISS. The fish lived in a space aquarium of ISS. Control medaka lived in same aquarium on the ground. After 2 weeks and 2 months of swimming in microgravity, medaka fish (N=5, each) were fixed in 4% paraformaldehyde at ISS. Cardiac morphology and structure were assessed by hematoxylin and eosin (HE), Azan and immuno-staining. The remaining 5 medaka fish, after 2 months at ISS, were treated by RNAlater for preservation of RNA for RT-PCR and RNA-Seq analysis. Results: The fishes at ISS were swimming in loops rather than straight line and tend to standstill. The body sizes were normal. Spaceflight heart looked normal without apparent histological abnormalities in 2 weeks samples. However, 2 month sampled spaceflight heart showed thinner cardiac fibers, exhibited circular lacunas and higher cardiac fibrosis. Using RNA-seq and RT-PCR, mRNA expression of cardiac contractile genes (myosin heavy chain, myosin light chain II and troponin T) were decreased in spaceflight heart. Interestingly, autophagy related genes (atg3, atg4, atg14 and atg16) expression were higher in spaceflight heart. However, Atg genes expressions were not changed in skeletal muscle. Although, myocardium mass was lower in spaceflight heart, mRNA expressions of muscle-specific ubiquitin ligases (MuRF1 and Atrogin1) and brain natriuretic peptide (BNP) were normal. Immuno-staining showed increased ULK1 expression in 2 weeks and LC3-II level (autophagosomes formation subtype) in 2 months spaceflight samples. Prolonged weightlessness produced substantial loss of cardiac fiber mass by autophagy. Conclusion: Microgravity increases autophagy related genes and decreases sarcomeric protein gene expression, which lead cardiac atrophy after prolonged spaceflight.
FRI0300 Bone Turnover and Fracture Risk Analysis in Patients with Prostate Cancer
Authors: J. Ivorra Cortés, C. Vera Donoso, D. Hervás Marín, L. González Puig, I. Chalmeta Verdejo, I. Martínez Cordellat, C. Núñez-Cornejo Piquer, R. Negueroles Albuixech, C.M. Feced Olmos, E. Labrador Sánchez, F.M. Ortiz Sanjuán, J.L. Valero Sanz, E. Grau García, K. Arévalo Ruales, C. Alcañiz Escandell, J.A. Román Ivorra
Journal: Annals of the Rheumatic Diseases (2015)

<h3>Background</h3> Prostate cancer is the most common male malignancy. Due to its condition of androgen-dependent cancer, the androgenic inhibition by LHRH agonists and/or testosterone receptors blockage are a basic treatment pillar. The loss of bone mass and the increased fracture risk are secondary effects of the anti-androgen therapy. On the other hand, prostate cancer incidence increases with age, so the affected population has a baseline high fracture risk. <h3>Objectives</h3> To analyze the bone turnover, osteoporosis prevalence and fracture risk in prostate cancer patients with and without anti-androgen therapy. <h3>Methods</h3> We included 45 prostate cancer patients from H.U.P La Fe that were visited consecutively by the rheumatologist to evaluate associated bone disease. Analytical parameters included were calcium, phosphorous, alkaline phosphatase, 25 OH vitamin D, PTH, P1NP and βCTX. Lower back and hipbone densitometry was performed in all patients. The fracture risk estimation was by the FRAX scoring system. A mixed linear regression model and a segmented regression model, as well as the Wilcoxon test, were used for statistical analysis. <h3>Results</h3> Patients mean age was 74 years (48-89). An osteoporosis prevalence of 18% and osteopenia prevalence of 40% was found in the densitometric analysis. Hipbone fracture risk evaluated by FRAX is higher than 3% in 10 patients (3 with densitometric osteoporosis and 7 with densitometric osteopenia. No results of patients having fracture risk evaluated by FRAX higher than 10% were found. 78% of the total number of patients was treated with LHRH agonists and 51% with bicalutamide (testosterone receptors blockers). LHRH agonist treatment interval showed a median of 3 months. Vitamin D values lower than 30ng/mL were observed in 73% of patients, and values lower than 15ng/mL were observed in 24% of patients. There was an inverse relationship between vitamin D and P1NP levels (P=0.0101). Moreover, there was an inverse relationship between P1NP and bCTX levels, and hipbone t-score (P=0.007 femoral neck and P=0.023 hipbone, and P=0.003 femoral neck and P=0.008 hipbone, respectively). Patients treated with LHRH agonists showed high P1NP levels (40.4ng/mL vs 29.4ng/mL; P=0.046) and bCTX levels (0.7ng/mL vs 0.3ng/mL; P=0.0006). <h3>Conclusions</h3> In our patients is remarkably the high prevalence of hypovitaminosis D (73%). LHRH agonist treatment increased bone turnover biomarker levels. The increase of these biomarkers is related to a hipbone mass decrease. FRAX score could help to identify high fracture risk patients with low bone density (osteopenia). <h3>Disclosure of Interest</h3> None declared
Rectal bleeding and colorectal cancer
Authors: T. Fahey
Journal: BMJ (2001)

Editor—Wauters et al report on the diagnostic value of rectal bleeding in terms of subsequent development of colorectal cancer.1 We feel that this study requires clarification for several reasons.

Firstly, the authors do not report the pre-test probability of colorectal cancer in age specific categories in their population. The diagnostic value of a symptom such as rectal bleeding and the impact on post-test probability and subsequent referral threshold are maximised when the pre-test probability of the disease is known.2

Secondly, they fail to mention that less than half of patients with rectal bleeding have no other symptoms.3 More often it is associated with other bowel symptoms that have higher diagnostic value than rectal bleeding alone.4

Thirdly, the reported positive likelihood ratio of 68.3 “rules in” a diagnosis of colorectal cancer, irrespective of the pre-test probability of the disease.2 The reported specificity of 99.5% has the same effect of ruling in the target disorder of colorectal cancer. These findings imply that any patients attending their general practitioner with rectal bleeding need referral and further evaluation. Our own clinical experience and other community based studies of rectal bleeding indicate that such a high specificity and likelihood ratio is unlikely and may well be misleading.4,5

Finally, the most likely explanation for the results relates to general practitioners underreporting rectal bleeding in the prospective arm of the study. Wauters et al chose “rectal bleeding as the reason for visiting a general practitioner” as the inclusion criterion for their study. They should clarify whether this means that patients in whom rectal bleeding was not the primary reason for consulting their general practitioner were excluded. A prospective study in the Netherlands showed that among patients presenting with rectal bleeding, 51% stated this as the primary reason for consulting their general practitioner; 49% consulted for a different reason, but rectal blood loss was subsequently mentioned during the consultation.4 Another prospective study found that 3% (95% confidence interval 1.4% to 5.8%) of patients with rectal bleeding subsequently developed colorectal cancer, and even in this study patients with “clinically relevant rectal bleeding” were overrepresented.5 In Wauters et al's study, 27 patients with rectal bleeding (7%, 4.6% to 10%) developed colorectal cancer.

In summary, there may have been a systematic bias in excluding less severe forms of rectal bleeding which may have not been the primary reason for consulting a general practitioner. This has resulted in inflated values for specificity and positive likelihood ratio. Before their results are incorporated into clinical practice Wauters et al should clarify their inclusion criteria and provide age specific two by two tables so that readers can judge for themselves the diagnostic value of isolated rectal bleeding in general practice.
GENO-30DISTINCT GENE EXPRESSION PROFILE THAT IS NOT A KNOWN SURVIVAL PREDICTOR IN TUMORS FROM LONG-TERM HIGH GRADE GLIOMA SURVIVORS TREATED WITH A RETROVIRAL REPLICATING VECTOR ENCODING YEAST CYTOSINE DEAMINASE
Authors: Derek Ostertag, Daniel Hogan, Michael Vogelbaum, Santosh Kesari, Steven Kalkanis, Tom Mikkelsen, Joseph Landolfi, J Bradley Elder, Clark Chen, Andreas Niethammer, Alice Chu, Douglas Jolly, Harry Gruber, Timothy Cloughesy
Journal: Neuro-Oncology (2015)

A dose escalating clinical study (NCT01985256) using a retroviral replicating vector (RRV), Toca 511, in combination with oral Toca FC (extended-release 5-fluorocytosine [5-FC]) is ongoing to evaluate safety and preliminary efficacy of this investigational therapy in patients with recurrent HGG. Toca 511 (vocimagene amiretrorepvec) encodes a yeast-derived, codon-optimized and heat-stabilized cytosine deaminase (CD) that converts 5-FC to the anti-cancer drug 5-FU in infected tumors. This virus replicates preferentially in malignant tissue and may have wide application in cancer therapies. In the study discussed here, Toca 511 is injected into resection cavity walls at time of tumor resection, and followed with multiple courses of Toca FC. RNA sequencing results in subject tumor samples reveal a unique gene expression profile associated with survival in Toca 511-treated subjects, which may be predictive. RNA expression profiles of resected tumors from 27 subjects were obtained via next-generation sequencing. Quality RNA sequencing results were obtained from two or three spatially distinct pieces of tumor from each subject. Expression profiles from separate regions of the same tumor were generally more similar to each other than to expression profiles of other subjects' tumors, but considerable heterogeneity was observed. A disproportionate number of the subjects that survived greater than one year displayed a unique expression subtype profile in multiple tumor samples that was distinct from normal brain and resembled samples isolated and analyzed in an orthogonal study from non-enhancing regions at the advancing edge of GBM tumors. Expression profiles that tracked with survival in the current study were not in general prognostic in orthogonal primary tumor datasets from TCGA and Rembrandt. These results suggest underlying molecular features and pathological stage of the tumor may help define the ability of Toca 511 and Toca FC therapy to prolong survival. Multivariate analysis using molecular and clinical factors will be presented.
Clinical Staging in Cancer of the Larynx: A Report on 788 Cases Using the American Joint Committee's Method of Stage Classification
Authors: Heise, Herman, Baylis, Paula
Journal: JNCI Journal of the National Cancer Institute (1966)

Journal Article Clinical Staging in Cancer of the Larynx: A Report on 788 Cases Using the American Joint Committee's Method of Stage Classification Get access Herman Heise, Herman Heise Biometry Branch, National Cancer Institute2, Bethesda, Maryland Search for other works by this author on: Oxford Academic PubMed Google Scholar Paula Baylis Paula Baylis Biometry Branch, National Cancer Institute2, Bethesda, Maryland Search for other works by this author on: Oxford Academic PubMed Google Scholar JNCI: Journal of the National Cancer Institute, Volume 36, Issue 1, January 1966, Pages 45–52, https://doi.org/10.1093/jnci/36.1.45 Published: 01 January 1966 Article history Received: 22 April 1965 Published: 01 January 1966
A phase I study of sequential versus concurrent interleukin-3 and granulocyte-macrophage colony-stimulating factor in advanced breast cancer patients treated with FLAC (5-fluorouracil, leucovorin, doxorubicin, cyclophosphamide) chemotherapy
Authors: JA O'Shaughnessy, DJ Venzon, M Gossard, MH Noone, A Denicoff, A Tolcher, D Danforth, J Jacobson, P Keegan, L Miller
Journal: Blood (1995)
Endoscopy evaluation to predict oral appliance outcomes in obstructive sleep apnoea
Authors: Kentaro Okuno, Yasuhiro Sasao, Kanji Nohara, Takayoshi Sakai, Benjamin T. Pliska, Alan A. Lowe, C. Frank Ryan, Fernanda R. Almeida
Journal: European Respiratory Journal (2016)

The objective of this study was to determine the utility of nasoendoscopy of the upper airway as a predictor of the efficacy of oral appliance treatment in obstructive sleep apnoea (OSA). A total of 61 consecutive patients with moderate-to-severe polysomnographically diagnosed OSA were recruited for this study. Using nasoendoscopy, we prospectively assessed the velopharynx and oro/hypopharynx in each patient while awake and in the supine position. We measured cross-sectional area (CSA), and anteroposterior and lateral diameters of the airway before and after mandibular advancement, and expressed the changes in dimensions as expansion ratios (after/before). We then compared the measurements of responders and nonresponders with oral appliance treatment. The expansion ratio (median (interquartile range)) for the CSA was greater in responders compared with nonresponders in the velopharynx (2.9 (2.3–5.0) versus 1.7 (1.5–1.9), p&lt;0.001) and in the oro/hypopharynx (3.4 (2.5–5.6) versus 2.4 (1.8–3.7), p&lt;0.05). Baseline apnoea–hypopnoea index and the CSA expansion ratio of the velopharynx were independent predictors of oral appliance treatment outcome based on a multivariate logistic regression analysis. The estimated area under the receiver operator characteristic curve was 0.87 and the cut-off value of the expansion ratio was 2.00. These results indicate that nasoendoscopy may have significant clinical utility in predicting the success of oral appliance treatment.
Case 29-2004
Authors: Adolf W. Karchmer, David F. Torchiana, Claudia U. Chae, Nadeem A. Afridi, Stuart L. Houser
Journal: New England Journal of Medicine (2004)

A 75-year-old woman with a history of aortic-valve stenosis and coronary artery disease awoke in the night with chest pain. The electrocardiogram showed ST-segment depression, and the troponin T levels were elevated. The chest pain resolved, but fever developed. Blood cultures were positive for the Streptococcus milleri group; fever persisted despite antibiotic therapy. A cardiologist, an infectious-disease specialist, and a cardiac surgeon discuss the diagnosis and management of this case.
Effect of Oxygen Tension on the Sensitivity of Normal and Tumor Tissues to Alkylating Agents&lt;xref ref-type="fn" rid="fn1"&gt;2&lt;/xref&gt;&lt;xref ref-type="fn" rid="fn2"&gt;3&lt;/xref&gt;
Authors: N BACK, J L AMBRUS
Journal: JNCI Journal of the National Cancer Institute (1963)

In view of the potentiation of the biologic effects of ionizing radiation by increased oxygen tension in tissues, the relationship of oxygen tension to the therapeutic and toxic actions of alkylating agents has been examined. Changes in oxygen concentration at 1 atmosphere of pressure from 8 to 100 percent did not alter the toxicity of nitrogen mustard to ICR/Ha mice. Similarly, no changes were seen when 100 percent oxygen was given at 2 to 5 atmospheres of pressure. Increase in oxygen tension in tissues was demonstrated by continuous polarography. This increase did not alter the effect of nitrogen mustard on increasing survival time or decreasing tumor growth of mice inoculated with Ehrlich adenocarcinoma, Sarcoma 180, and Leukemia L1210 in either the ascites or the solid form. Exposure of ascites tumors to nitrogen mustard in vitro produced equal prolongation of survival time of the recipient mice whether exposure was undertaken under normal atmospheric conditions or increased oxygen tension. With paramagnetic resonance spectroscopy, no free radicals were detected in frozen solutions of nitrogen mustard, chlorambucil, triethylenemelamine, busulfan, and triethylenethiophosphoramide. Mechanisms of the biologic effects of alkylating agents as compared to those of ionizing radiation are discussed.
Moral dimensions
Authors: Torbjörn Tännsjö
Journal: BMJ (2005)

<i>Doctors in the United Kingdom can accompany their patients every step of the way, up until the last. The law stops them helping their patients take the final step, even if that is the patient9s fervent wish. Next month9s debate in the House of Lords could begin the process of changing the law. To help doctors decide where they stand we publish a range of opinions</i>
Letter by Chan Regarding Article, “The Utility of Therapeutic Hypothermia for Post–Cardiac Arrest Syndrome Patients With an Initial Nonshockable Rhythm”
Authors: Paul S. Chan
Journal: Circulation (2016)

Using data from the 6-center Penn Alliance for Therapeutic Hypothermia (PATH) registry, Perman et al 1 found that patients with a nonshockable cardiac arrest treated with therapeutic hypothermia had a ≈3-fold increased odds of both survival to hospital discharge and favorable neurological survival.The authors posited that their analysis was more rigorous than previous observational studies, because they used a propensity score analysis to mimic a quasi-experimental design.Although the authors are to be lauded for addressing this important clinical question, their analyses are limited in several ways.First, a propensity score is only as useful as the measured covariates for which it accounts.The propensity score in this study adjusted for only 5 variables: age, sex, location of arrest, witnessed arrest, and duration of arrest.None of these variables reflect patients' severity of illness, especially among those with in-hospital cardiac arrest, and the latter 3 variables pertain to only out-of-hospital cardiac arrest.Given the paucity of variables in deriving the propensity score in this study, differences in unmeasured covariates between treated and untreated patients could have affected survival outcomes.Second, did the authors consider including in their propensity score 2 variables they did have at their disposal-the calendar year of the arrest and the PATH hospital site?Their Figure 1 shows that many patients from the nonhypothermia cohort were from years 2000 to 2007, whereas the hypothermia cohort did not have any cases before 2005, and the patients in that cohort were enrolled mostly after 2007.Because out-of-hospital and in-hospital cardiac arrest survival have both improved during this time period, 2,3 nonadjustment of the year of cardiac arrest may have biased their results.Moreover, given that significant variation in cardiac arrest survival has been documented among hospitals, 4 it would only strengthen their results if they had included the PATH hospital site (and the year of the arrest, as well) in their propensity score model.Results of previous studies of hypothermia treatment for nonshockable cardiac arrest rhythms have varied widely. 5Given the small sample size and the limited number of variables for propensity score adjustment in this study, the verdict remains inconclusive as to whether patients with cardiac arrests attributable to asystole or pulseless electric activity benefit from hypothermia treatment.Short of a large clinical trial, a much larger cohort study that uses a robust propensity score that can adequately adjust for patient severity of illness remains a high priority to demonstrate the effectiveness of hypothermia treatment for patients with nonshockable cardiac arrest rhythms.
Diagnosis of cholangiocarcinoma in primary sclerosing cholangitis: finding a needle in a haystack
Authors: Udayakumar Navaneethan
Journal: Endoscopy (2016)

Primary sclerosing cholangitis (PSC) is a chronic inflammatory disease of the biliary tree, characterized by fibrosis and stricturing of the bile ducts and leading to cirrhosis [1]. It is a premalignant disease that confers a significant risk for the development of cholangiocarcinoma (CCA) [2] [3]. The risk of CCA among patients with PSC is increased 400-fold compared with the general population, with a 20 % lifetime risk, and CCA remains one of the leading causes of liver-related mortality in this patient population [2] [3].
Risk Factors That Discriminate 'High-Risk' From 'Low-Risk' Japanese Patients With Coronary Artery Disease
Authors: Kunihisa Miwa, Keiko Nakagawa
Journal: Circulation (2000)

Although various risk factors have been implicated in the progression of coronary artery disease (CAD), coronary risk factors specifically related to the long-term prognosis for high-risk CAD have not been determined. The study enrolled 311 consecutive Japanese patients with CAD who underwent diagnostic coronary arteriography and divided them into 2 groups: (i) 135 high-risk patients with either impaired left ventricular function (ejection fraction <50%) or multivessel disease and (ii) 176 low-risk patients with normal left ventricular function and 0- or 1-vessel disease. The prevalence of risk factors including age, gender, smoking, hypertension, diabetes mellitus (DM), obesity and lipid variables were compared between the 2 groups. The prevalence of DM, a serum high-density lipoprotein (HDL)-cholesterol level below 35 mg/dl and a serum lipoprotein (Lp) (a) level above 25 mg/dl was significantly higher in the high-risk group as compared with the low-risk group. Multiple logistic regression analysis demonstrated that DM (odds ratio (OR): 1.72, 95% confidence intervals (CI): 1.02-2.92, p<0.05), a low HDL-cholesterol level (OR: 2.49, 95% CI: 1.49-4.17, p<0.001) and a high Lp(a) level (OR: 1.68, 95% CI: 1.02-2.76, p<0.05) were all independent risk factors for high-risk CAD. However, if the patients with 0-vessel disease were excluded from the low-risk group, a low HDL-cholesterol level was found to be the only independent predictor for high-risk CAD (OR: 2.07, 95% CI: 1.15-3.70, p<0.05). Among both men and smokers in this population, a higher Lp(a) level was found to be a significant predictor for high-risk CAD. A low serum level of HDL-cholesterol, a high serum level of Lp(a) and DM were significant predictors of high-risk in patients with CAD. Among patients with a significant coronary stenosis or left ventricular dysfunction, a low serum level of HDL-cholesterol was the only significant predictor for high-risk CAD.