tbuckley/cabot-search huggingface dataset:
Avoiding the effect of BCG vaccination in detecting Mycobacterium tuberculosis infection with a blood test
Authors: R. Diel
Journal: European Respiratory Journal (2006)

Bacille Calmette-Guérin (BCG) vaccination can confound tuberculin skin test (TST) reactions in the diagnosis of latent tuberculosis infection (LTBI). The TST was compared with a Mycobacterium tuberculosis (MTB)-specific enzyme-linked immunospot (ELISPOT) assay during an outbreak of MTB infection at a police academy in Germany. Participants were grouped according to their risk of LTBI in close (n = 36) or occasional (n = 333) contacts to the index case. For the TST, the positive response rate was 53% (19 out of 36) among close and 16% (52 out of 333) among occasional contacts. In total, 56 TST-positive contacts (56 out of 71 = 78.9%) and 27 TST-negative controls (27 out of 298 = 9.1%) underwent ELISPOT testing. The odds ratio (OR) of a positive test result across the two groups was 29.2 (95% confidence interval (CI) 3.5-245.0) for the ELISPOT and 19.7 (95% CI 2.0-190.2) for the TST with a 5 mm cut-off. Of 369 contacts, 158 (42.8%) had previously received BCG vaccination. The overall agreement between the TST and the ELISPOT was low, and positive TST reactions were confounded by BCG vaccination (OR 4.8 (95% CI 1.3-18.0)). In contrast, use of a 10-mm induration cut-off for the TST among occasional contacts showed strong agreement between TST and ELISPOT in nonvaccinated persons. In bacille Calmette-Guérin-vaccinated individuals, the Mycobacterium tuberculosis-specific enzyme-linked immunospot assay is a better indicator for the risk of latent tuberculosis infection than the tuberculin skin test.
Association of Pretransplant Glycemic Control With Posttransplant Outcomes in Diabetic Kidney Transplant Recipients
Authors: Miklos Z. Molnar, Edmund Huang, Junichi Hoshino, Mahesh Krishnan, Allen R. Nissenson, Csaba P. Kovesdy, Kamyar Kalantar-Zadeh
Journal: Diabetes Care (2011)

Observational studies have yielded inconsistent findings regarding the association of hemoglobin A(1c) (HbA(1c)) with survival in diabetic patients on dialysis. The association between pretransplant glycemic control and short- and long-term posttransplant outcomes in kidney transplant recipients is not clear.Linking the 5-year patient data of a large dialysis organization (DaVita) to the Scientific Registry of Transplant Recipients, we identified 2,872 diabetic dialysis patients who underwent first kidney transplantation. Mortality or graft failure and delayed graft function (DGF) risks were estimated by Cox regression (hazard ratio [HR]) and logistic regression (odds ratio), respectively.Patients were 53 ± 11 years old and included 36% women and 24% African Americans. In our fully adjusted model, allograft failure-censored, all-cause death HR and 95% CI for time-averaged pretransplant HbA(1c) categories of 7 to <8%, 8 to <9%, 9 to 10%, and ≥10%, compared with 6 to <7% (reference), were 0.89 (0.59-1.36), 2.06 (1.31-3.24), 1.41 (0.73-2.74), and 3.43 (1.56-7.56), respectively; and graft failure-censored cardiovascular death HR was 0.38 (0.13-1.05), 1.78 (0.69-4.55), 1.59 (0.44-5.76), and 4.28 (0.85-21.64), respectively. We did not find any difference in risk of death-censored graft failure or DGF with different pretransplant HbA(1c) levels.Poor pretransplant glycemic control appears associated with decreased posttransplant survival in kidney transplant recipients, whereas allograft outcomes may not be affected.
Radiofrequency Ablation as Initial Therapy in Paroxysmal Atrial Fibrillation
Authors: Jens Cosedis Nielsen, Arne Johannessen, Pekka Raatikainen, Gerhard Hindricks, Håkan Walfridsson, Ole Kongstad, Steen Pehrson, Anders Englund, Juha Hartikainen, Leif Spange Mortensen, Peter Steen Hansen
Journal: New England Journal of Medicine (2012)

There are limited data comparing radiofrequency catheter ablation with antiarrhythmic drug therapy as first-line treatment in patients with paroxysmal atrial fibrillation.We randomly assigned 294 patients with paroxysmal atrial fibrillation and no history of antiarrhythmic drug use to an initial treatment strategy of either radiofrequency catheter ablation (146 patients) or therapy with class IC or class III antiarrhythmic agents (148 patients). Follow-up included 7-day Holter-monitor recording at 3, 6, 12, 18, and 24 months. Primary end points were the cumulative and per-visit burden of atrial fibrillation (i.e., percentage of time in atrial fibrillation on Holter-monitor recordings). Analyses were performed on an intention-to-treat basis.There was no significant difference between the ablation and drug-therapy groups in the cumulative burden of atrial fibrillation (90th percentile of arrhythmia burden, 13% and 19%, respectively; P=0.10) or the burden at 3, 6, 12, or 18 months. At 24 months, the burden of atrial fibrillation was significantly lower in the ablation group than in the drug-therapy group (90th percentile, 9% vs. 18%; P=0.007), and more patients in the ablation group were free from any atrial fibrillation (85% vs. 71%, P=0.004) and from symptomatic atrial fibrillation (93% vs. 84%, P=0.01). One death in the ablation group was due to a procedure-related stroke; there were three cases of cardiac tamponade in the ablation group. In the drug-therapy group, 54 patients (36%) underwent supplementary ablation.In comparing radiofrequency ablation with antiarrhythmic drug therapy as first-line treatment in patients with paroxysmal atrial fibrillation, we found no significant difference between the treatment groups in the cumulative burden of atrial fibrillation over a period of 2 years. (Funded by the Danish Heart Foundation and others; MANTRA-PAF ClinicalTrials.gov number, NCT00133211.).
Evaluation Of Basal Serum Tryptase And Mastocytosis In Patients With Anaphylaxis Caused By Food Or Drug Allergy
Authors: B. Caruso, M. Pagani, R. Zanotti, P. Bonadonna, E. Olivieri, A. Dama, M. Schiappoli, G. Senna, A. Antico, G. Passalacqua
Journal: Journal of Allergy and Clinical Immunology (2009)
Oncogenic role of the ubiquitin ligase subunit Skp2 in human breast cancer
Authors: Sabina Signoretti, Lucia Di Marcotullio, Andrea Richardson, Sridhar Ramaswamy, Beth Isaac, Montserrat Rue, Franco Monti, Massimo Loda, Michele Pagano
Journal: Journal of Clinical Investigation (2002)

Estrogen receptor (ER) expression and Her-2 amplification define specific subsets of breast tumors for which specific therapies exist. The S-phase kinase-associated protein Skp2 is required for the ubiquitin-mediated degradation of the cdk-inhibitor p27 and is a bona fide proto-oncoprotein. Using microarray analysis and immunohistochemistry, we determined that higher levels of Skp2 are present more frequently in ER-negative tumors than in ER-positive cases. Interestingly, the subset of ER-negative breast carcinomas overexpressing Skp2 are also characterized by high tumor grade, negativity for Her-2, basal-like phenotype, high expression of certain cell cycle regulatory genes, and low levels of p27 protein. We also found that Skp2 expression is cell adhesion-dependent in normal human mammary epithelial cells but not in breast cancer cells and that an inhibition of Skp2 induces a decrease of adhesion-independent growth in both ER-positive and ER-negative cancer cells. Finally, forced expression of Skp2 abolished effects of antiestrogens, suggesting that deregulated Skp2 expression might play a role in the development of resistance to antiestrogens. We conclude that Skp2 has oncogenic potential in breast epithelial cells and is overexpressed in a subset of breast carcinomas (ER- and Her-2 negative) for which Skp2 inhibitors may represent a valid therapeutic option.
The Epilepsy-Linked Lgi1 Protein Assembles into Presynaptic Kv1 Channels and Inhibits Inactivation by Kvβ1
Authors: Uwe Schulte, Jörg-Oliver Thumfart, Nikolaj Klöcker, Claudia A. Sailer, Wolfgang Bildl, Martin Biniossek, Doris Dehn, Thomas Deller, Silke Eble, Karen Abbass, Tanja Wangler, Hans-Günther Knaus, Bernd Fakler
Journal: Neuron (2006)
Management of rib pain in rowers: emerging issues
Authors: Anders Vinther, Jane S Thornton
Journal: British Journal of Sports Medicine (2015)

Rib stress fracture (RSF) is one of the most hotly debated and least understood of all rowing injuries. It has recently been stated that ‘the pathology and prevention of rib stress fractures will be one of the most useful areas of research in rowing injuries’.1 There is a pressing need for more quality research of RSF aetiology and epidemiology that will inform effective prevention strategies. The current ‘best practice’ management of RSF is principally based on clinical experience and expert opinions from the 20th century.2–4 This is likely due to few major advances within the field of stress fracture healing. Current management strategies, therefore, focus mainly on fitness maintenance and a graded return to rowing.

As previously described2 ,3 a pain-dependent approach is taken, involving a period of complete rest until breathing deeply remains pain free, a period of non-rowing exercise—that is, stationary bicycling and lower extremity strength training—and, eventually, a gradual return …
Oxidant-induced DNA damage of target cells.
Authors: I Schraufstätter, P A Hyslop, J H Jackson, C G Cochrane
Journal: Journal of Clinical Investigation (1988)

In this study we examined the leukocytic oxidant species that induce oxidant damage of DNA in whole cells. H2O2 added extracellularly in micromolar concentrations (10-100 microM) induced DNA strand breaks in various target cells. The sensitivity of a specific target cell was inversely correlated to its catalase content and the rate of removal of H2O2 by the target cell. Oxidant species produced by xanthine oxidase/purine or phorbol myristate acetate-stimulated monocytes induced DNA breakage of target cells in proportion to the amount of H2O2 generated. These DNA strand breaks were prevented by extracellular catalase, but not by superoxide dismutase. Cytotoxic doses of HOCl, added to target cells, did not induce DNA strand breakage, and myeloperoxidase added extracellularly in the presence of an H2O2-generating system, prevented the formation of DNA strand breaks in proportion to its H2O2 degrading capacity. The studies also indicated that H2O2 formed hydroxyl radical (.OH) intracellularly, which appeared to be the most likely free radical responsible for DNA damage: .OH was detected in cells exposed to H2O2; the DNA base, deoxyguanosine, was hydroxylated in cells exposed to H2O2; and intracellular iron was essential for induction of DNA strand breaks.
Paracrine Hedgehog Signaling Drives Metabolic Changes in Hepatocellular Carcinoma
Authors: Isaac S. Chan, Cynthia D. Guy, Yuping Chen, Jiuyi Lu, Marzena Swiderska-Syn, Gregory A. Michelotti, Gamze Karaca, Guanhua Xie, Leandi Krüger, Wing-Kin Syn, Blair R. Anderson, Thiago A. Pereira, Steve S. Choi, Albert S. Baldwin, Anna Mae Diehl
Journal: Cancer Research (2012)

Hepatocellular carcinoma (HCC) typically develops in cirrhosis, a condition characterized by Hedgehog (Hh) pathway activation and accumulation of Hh-responsive myofibroblasts. Although Hh signaling generally regulates stromal-epithelial interactions that support epithelial viability, the role of Hh-dependent myofibroblasts in hepatocarcinogenesis is unknown. Here, we used human HCC samples, a mouse HCC model, and hepatoma cell/myofibroblast cocultures to examine the hypothesis that Hh signaling modulates myofibroblasts' metabolism to generate fuels for neighboring malignant hepatocytes. The results identify a novel paracrine mechanism whereby malignant hepatocytes produce Hh ligands to stimulate glycolysis in neighboring myofibroblasts, resulting in release of myofibroblast-derived lactate that the malignant hepatocytes use as an energy source. This discovery reveals new diagnostic and therapeutic targets that might be exploited to improve the outcomes of cirrhotic patients with HCCs.
Sex and Race Differences in Right Ventricular Structure and Function
Authors: Steven M. Kawut, João A.C. Lima, R. Graham Barr, Harjit Chahal, Aditya Jain, Harikrishna Tandri, Amy Praestgaard, Emilia Bagiella, Jorge R. Kizer, W. Craig Johnson, Richard A. Kronmal, David A. Bluemke
Journal: Circulation (2011)

Background— Right ventricular (RV) morphology is an important predictor of outcomes in heart and lung disease; however, determinants of RV anatomy have not been well studied. We examined the demographic factors associated with RV morphology and function in a population-based multiethnic sample free of clinical cardiovascular disease. Methods and Results— In the Multi-Ethnic Study of Atherosclerosis (MESA), cardiac magnetic resonance imaging was performed on 5098 participants. Right ventricular volumes and mass were available for 4204 participants. Normative equations for RV parameters were derived with an allometric approach. The study sample (n=4123) was 61.5±10.1 years of age and 47.5% men. Older age was associated with lower RV mass (≈5% lower mass per decade), with larger age-related decrements in men than in women ( P &lt;0.05 for interaction). Older age was also associated with higher RV ejection fraction, an association that differed between races/ethnicities ( P ≤0.01 for interaction). Overall, men had greater RV mass (≈8%) and larger RV volumes than women, but had lower RV ejection fraction (4% in absolute terms; P &lt;0.001). Blacks had lower RV mass than whites ( P ≤0.002), whereas Hispanics had higher RV mass ( P ≤0.02). When the derived normative equations were used, 7.3% (95% confidence interval, 6.5 to 8.1) met the criteria for RV hypertrophy, and 5.9% (95% confidence interval, 5.2 to 6.6) had RV dysfunction. Conclusion— Age, sex, and race are associated with significant differences in RV mass, RV volumes, and RV ejection fraction, potentially explaining distinct responses of the RV to cardiopulmonary disease.
Comparative study between Delorme operation with or without postanal repair and levateroplasty in treatment of complete rectal prolapse
Authors: Mohamed Youssef, Waleed Thabet, Ayman El Nakeeb, Alaa Magdy, Emad Abd Alla, Mahmoud Abd El Nabeey, El Yamani Fouda, Waleed Omar, Mohamed Farid
Journal: International Journal of Surgery (2012)
Cardiac shunt in COPD as a cause of severe hypoxaemia: probably not so uncommon after all
Authors: B.G. Boerrigter, A. Boonstra, N. Westerhof, P.E. Postmus, A. Vonk-Noordegraaf
Journal: European Respiratory Journal (2011)

Cardiac shunt in COPD as a cause of severe hypoxaemia: probably not so uncommon after all
Successful treatment of choking.
Authors: N Richards
Journal: BMJ (1976)

wound primarily in perforated appendicitis and possibly in purulent and gangrenous cases too.(When else would one sew up tissues steeped in faecal pus ?)An acceptable alterna- tive is delayed primary suture, with a wet gauze pack to the intermuscular layers for four days.I am grateful to my colleagues who kindly allowed me to examine their patients' records, so illustrating the need for another look at appendicectomy.
Formula One and global road safety
Authors: I. Roberts
Journal: Journal of the Royal Society of Medicine (2007)

Formula One, motorist organizations and car makers have manoeuvred themselves into pole position in global road safety politics. The FIA, the governing body of motor sport, has established a Commission for Global Road Safety that aims to set the policy agenda for road safety in poor countries.1 Formula One's ability to access and influence leading political figures has undoubtedly raised the profile of road traffic crashes as a global public health crisis, but the policies it promotes are neither the most effective in preventing injury, nor the most environmentally sustainable.
Hyposplenism in Primary Systemic Amyloidosis
Authors: MORIE A. GERTZ
Journal: Annals of Internal Medicine (1983)

Twenty-two of 91 (24%) patients with primary systemic amyloidosis were functionally hyposplenic. This group, identified by blood smear findings, had a different survival distribution when compared with a normosplenic group (p < 0.0001). The peripheral blood smear was more sensitive than the splenic scan for a diagnosis of hyposplenism. Amyloidosis should be included in the differential diagnosis of acquired hyposplenism in the adult.
Calcium Movements, Distribution, and Functions in Smooth Muscle
Authors: H Karaki, H Ozaki, M Hori, M Mitsui-Saito, K Amano, K Harada, S Miyamoto, H Nakazawa, K J Won, K Sato
Journal: Pharmacological Reviews (1997)

Contraction of smooth muscle is regulated by the cytosolic Ca2+ level ([Ca2+]i)b, and the sensitivity to Ca2+ of the contractile elements in response to changes in the environment surrounding the cell. The first sequence of events in regulation includes the binding of endogenous substances, such as
Acute tropical polyarthritis in Zimbabwe: a prospective search for a gonococcal aetiology.
Authors: C M Stein, M G Hanly
Journal: Annals of the Rheumatic Diseases (1987)

Fifteen consecutive patients with acute arthritis were studied. Careful culture and microscopy of swabs from mucosal sites were performed to examine the hypothesis that the acute tropical polyarthritis commonly seen in Zimbabwe is due to undiagnosed gonococcal infection. Rheumatic fever and Reiter9s disease accounted for two cases each. Gram negative intracellular diplococci were found in three patients who would otherwise have been diagnosed as having tropical polyarthritis. Except for two of the remaining eight patients, who had raised anti-streptolysin O titres suggesting recent streptococcal infection, no explanation for the arthritis was found. The clinical entity of tropical polyarthritis may not be due to a single aetiological agent.
An Experimentally Determined Evolutionary Model Dramatically Improves Phylogenetic Fit
Authors: Jesse D. Bloom
Journal: Molecular Biology and Evolution (2014)

All modern approaches to molecular phylogenetics require a quantitative model for how genes evolve. Unfortunately, existing evolutionary models do not realistically represent the site-heterogeneous selection that governs actual sequence change. Attempts to remedy this problem have involved augmenting these models with a burgeoning number of free parameters. Here, I demonstrate an alternative: Experimental determination of a parameter-free evolutionary model via mutagenesis, functional selection, and deep sequencing. Using this strategy, I create an evolutionary model for influenza nucleoprotein that describes the gene phylogeny far better than existing models with dozens or even hundreds of free parameters. Emerging high-throughput experimental strategies such as the one employed here provide fundamentally new information that has the potential to transform the sensitivity of phylogenetic and genetic analyses.
CD103+ pulmonary dendritic cells preferentially acquire and present apoptotic cell–associated antigen
Authors: A. Nicole Desch, Gwendalyn J. Randolph, Kenneth Murphy, Emmanuel L. Gautier, Ross M. Kedl, Mireille H. Lahoud, Irina Caminschi, Ken Shortman, Peter M. Henson, Claudia V. Jakubzick
Journal: The Journal of Experimental Medicine (2011)

Cells undergoing programmed cell death (apoptosis) are removed in situ by macrophages and dendritic cells (DCs) through a specialized form of phagocytosis (efferocytosis). In the lung, there are two primary DC subsets with the potential to migrate to the local lymph nodes (LNs) and initiate adaptive immune responses. In this study, we show that only CD103+ DCs were able to acquire and transport apoptotic cells to the draining LNs and cross present apoptotic cell–associated antigen to CD8 T cells. In contrast, both the CD11bhi and the CD103+ DCs were able to ingest and traffic latex beads or soluble antigen. CD103+ DCs selectively exhibited high expression of TLR3, and ligation of this receptor led to enhanced in vivo cytotoxic T cell responses to apoptotic cell–associated antigen. The selective role for CD103+ DCs was confirmed in Batf3−/− mice, which lack this DC subtype. Our findings suggest that CD103+ DCs are the DC subset in the lung that captures and presents apoptotic cell–associated antigen under homeostatic and inflammatory conditions and raise the possibility for more focused immunological targeting to CD8 T cell responses.
Crashes involving young drivers
Authors: S. Jones, F. McKenna, S. Stradling, N. Christie, T. Mullarkey, D. Davies, E. Box, J. Townsend, J. Dalton
Journal: BMJ (2015)

Still waiting for government action despite their costs in lives and money

A year after our call to the UK government to take urgent action to reduce deaths and injuries associated with young drivers1 there has been no progress. In the two years since the government’s promise of a green paper on young drivers’ safety, it is estimated that we could have avoided almost 9000 people being injured in road crashes involving young drivers, with 866 seriously or fatally injured and at a cost of £400m (€530m; $600m).2

One of the suggested reasons for delay is enthusiasm for motor insurance policies based on telematics or black box technology. This technology could play an important part in reducing young driver crashes, but it is unlikely to be the whole solution; telematics does not assess the presence of passengers, their behaviour, or their alcohol consumption. It will take some years to show the effect of telematics on crashes and casualties. Current users are self selected and may be significantly different from non-users. In the meantime, deaths and injuries are still occurring, and one intervention has repeatedly been shown to be effective—graduated licensing. …