tbuckley/cabot-search huggingface dataset:
Screening for latent tuberculosis infection: performance of tuberculin skin test and interferon-γ release assays under real-life conditions
Authors: S Kleinert, H-P Tony, K Krueger, J Detert, F Mielke, K Rockwitz, R Schwenke, G R Burmester, R Diel, M Feuchtenberger, C Kneitz
Journal: Annals of the Rheumatic Diseases (2012)

Objectives To characterise optimal screening strategies for latent tuberculosis infection (LTBI) prior to the initiation of anti-tumour necrosis factor therapy. Methods Patients in 62 German rheumatology centres were evaluated for LTBI. Each patient was screened with a tuberculin skin test (TST) and one form of an interferon-γ release assay (IGRA), either TSPOT.TB (TSPOT) or Quantiferon TB Gold (QFT). Results A total of 1529 patients with rheumatological disease were tested with a TST, 844 with TSPOT and 685 with QFT. TST was positive in 11.3% (n=173). The prevalence of LTBI was 8.0% when defined as a positive TST and no previous Bacille Calmette-Guérin (BCG) vaccination and 7.9% when based on a positive IGRA. Combining both estimates increased the prevalence of LTBI to 11.1%. Clinical risk factors for LTBI were found in 122 patients (34 with a history of prior TB, 81 close contacts and 27 with suggestive chest x-ray lesions). A compound risk factor (CRF) was defined as the presence of at least one of these three risk factors. Statistical analyses were conducted to examine the association between CRF and LTBI test outcomes. In multivariate analysis, TST was influenced by CRF (OR 6.2; CI 4.08 to 9.44, p&lt;0.001) and BCG vaccination status (OR 2.9; CI 2.00 to 4.35, p&lt;0.001). QFT and TSPOT were only influenced by CRF (QFT: OR 2.6; CI 1.15 to 5.98, p=0.021; TSPOT: OR 8.7; CI 4.83 to 15.82, p&lt;0.001). ORs and the agreement of TST and IGRA test results varied by rheumatological disease. Conclusion LTBI test results in an individual patient need to be considered in the context of prior BCG vaccination and clinical risk factors. In patient populations with low rates of TB incidence and BCG vaccination, the use of both TST and IGRA may maximise sensitivity in detecting LTBI but may also reduce specificity.
Contribution of H. pylori and Smoking Trends to US Incidence of Intestinal-Type Noncardia Gastric Adenocarcinoma: A Microsimulation Model
Authors: Jennifer M. Yeh, Chin Hur, Deb Schrag, Karen M. Kuntz, Majid Ezzati, Natasha Stout, Zachary Ward, Sue J. Goldie
Journal: PLoS Medicine (2013)

Jennifer Yeh and colleagues examine the contribution of IHelicobacter pyloriI and smoking trends to the incidence of past and future intestinal-type noncardia gastric adenocarcinoma. Please see later in the article for the Editors' Summary
Mutations in PROP1 cause familial combined pituitary hormone deficiency
Authors: Wei Wu, Joy D. Cogan, Roland W. Pfäffle, Jeremy S. Dasen, Herwig Frisch, Shawn M. O'Connell, Sarah E. Flynn, Milton R. Brown, Primus E. Mullis, John S. Parks, John A. Phillips III, Michael G. Rosenfeld
Journal: Nature Genetics (1998)
Prophylaxis of early ventricular fibrillation by inhibition of acylcarnitine accumulation.
Authors: P B Corr, M H Creer, K A Yamada, J E Saffitz, B E Sobel
Journal: Journal of Clinical Investigation (1989)

Hypoxia in isolated myocytes results in accumulation of long-chain acylcarnitines (LCA) in sarcolemma. Inhibition of carnitine acyltransferase I (CAT-I) with sodium 2-[5-(4-chlorophenyl)-pentyl]-oxirane-2-carboxylate (POCA) prevents both the accumulation of LCA in the sarcolemma and the initial electrophysiologic derangements associated with hypoxia. Another amphiphilic metabolite, lysophosphatidylcholine (LPC), accumulates in the ischemic heart in vivo, in part because of inhibition of its catabolism by accumulating LCA. It induces electrophysiologic alterations in vitro analogous to early changes induced by ischemia in vivo. The present study was performed to determine whether POCA could prevent accumulation of both LCA and LPC induced by ischemia in vivo and if so, whether attenuation of early arrhythmogenesis would result. LAD coronary artery occlusions were induced for 5 min in chloralose-anesthetized cats. Coronary occlusion in untreated control animals elicited prompt, threefold increases of LCA (73 +/- 8 to 286 +/- 60 pmol/mg protein) and twofold increase of LPC (3.3 +/- 0.4 to 7.5 +/- 0.9 nmol/mg protein) selectively in the ischemic zone, associated with ventricular tachycardia (VT) or ventricular fibrillation (VF) occurring within the 5-min interval before acquisition of myocardial samples in 64% of the animals. POCA prevented the increase of both LCA and LPC. It also prevented the early occurrence of VT or VF (within 5 min of occlusion) in all animals studied. The antiarrhythmic effect of POCA was not attributable to favorable hemodynamic changes or to changes in myocardial perfusion measured with radiolabeled microspheres. Thus, inhibition of CAT-I effectively reduced the incidence of lethal arrhythmias induced early after the onset of ischemia. Accordingly, pharmacologic inhibition of this enzyme provides a promising approach for prophylaxis of sudden cardiac death, that typically occurs very soon after the onset of acute ischemia, in man.
REM (Risk of Endometrial Malignancy): A Proposal for a New Scoring System to Evaluate Risk of Endometrial Malignancy
Authors: Roberto Angioli, Stella Capriglione, Alessia Aloisi, Daniela Luvero, Ester Valentina Cafà, Nella Dugo, Roberto Montera, Carlo De Cicco Nardone, Corrado Terranova, Francesco Plotti
Journal: Clinical Cancer Research (2013)

Abstract Purpose: It is often difficult to distinguish a benign endometrial disease from a malignancy and tools to help the physician are needed to triage patients into high and low risk of endometrial cancer. The purpose of this study was to obtain a predictive model to assess the risk of endometrial malignancy (REM) in women with ultrasound endometrial abnormalities. Experimental Design: Women, between ages 45 to 80 years, diagnosed through ultrasound with endometrial abnormalities and scheduled to have surgery were enrolled on a prospective study at the Department of Gynaecologic Oncology of Campus Bio-Medico, University of Rome. Preoperative clinical, ultrasound and laboratory characteristics were taken into account. Logistic regression algorithm was used to categorize patients into low- and high-risk groups for endometrial cancer. Results: A total of 675 patients were considered for the analysis: 88 with endometrial cancer and 587 with benign endometrial disease. We divided the patients into two groups: training set (TS) and verification set (VS). Preoperative age, symptom, HE4 levels, and ultrasound endometrial thickness were found statistically significant, and were included into a multivariate logistic regression model to determine the probability to have endometrial cancer. In the TS, REM reported 93.3% sensitivity and 97.1% specificity [positive predictive value (PPV), 0.83; negative predictive value (NPV), 0.98; AUC, 0.957; 95% confidence interval (CI), 0.908–0.984]. In the VS, REM reported 89.3% sensitivity and 95.4% specificity (PPV, 0.73; NPV, 0.98; AUC, 0.919; 95% CI, 0.829–0.970). Conclusions: Our data support the use of REM to triage patients into low- and high-risk groups for endometrial cancer, even if an external validation of the model is needed. Clin Cancer Res; 19(20); 5733–9. ©2013 AACR.
Morphologic characteristics of erythroleukemia (Acute Myeloid Leukemia; FAB‐M6): A CALGB study
Authors: F. R. Davey, N. Abraham, V. L. Brunetto, J. M. Maccallum, D. A. Nelson, E. D. Ball, J. D. Griffin, M. R. Baer, D. Wurster‐Hill, R. J. Mayer, C. A. Schiffer, C. D. Bloomfield
Journal: American Journal of Hematology (1995)

Abstract We have reviewed the clinical, morphologic, immunophenotypic, and cytogenetic features of 52 patients with erythroleukemia (FAB Cooperative Group; AML‐M6) studied by the Cancer and Leukemia Group B (CALGB). The purpose of this study was to correlate morphology with the clinical features, immunophenotypes, and karyotypes of neoplastic cells, and with the response to therapy of patients with AML‐M6. Thirty‐three patients (63%) were male, median age 59 (range 16‐81) years, 47 patients (90%) were white, and 42 patients (81%) had a performance status of &lt;2. Myelodysplastic changes were observed in at least 1 cell lineage in all cases, and in 2 cell lineages in 45 of 52 (86%) cases. Fifty percent or more of cases studied were positive for CD11b, CD13, CD15, CD33, glycophorin‐A, and HLA‐DR markers. Fourteen of 27 cases (52%) in whom karyotypic analyses were conducted had cytogenetic abnormalities. Five (19%) were simple (&lt;3 karyotypic abnormalities), while 9 (33%) were complex (≥ abnormalities). We observed either a complete or partial loss of chromosomes 5, 7, or 12p, or the presence of trisomy 8, in 11 of 27 (41%) patients. Cases of AML‐M6 were divided into group 1 (14 patients with bone marrow proerythroblasts and basophilic erythroblasts &gt;25% of all erythroblasts) and group 2 (38 patients with proerythroblasts and basophilic erythroblasts ≤25% of all erythroblasts). We observed no significant differences between groups 1 and 2 in regard to sex, age, race, performance status, percentage of blood erythroblasts or myeloblasts, percentage of bone marrow erythroblasts, and periodic acid‐Schiff (PAS) or myelodysplasia scores. Six of 6 (100%) patients of group 1, and 7 of 21 (33%) patients of group 2, had normal karyotypes (P = .006). Nine of 13 (69%) patients of group 1 and 15 of 33 (45%) patients of group 2 had a complete remission (CR) (P = .2). Eight of 11 (73%) cytogenetically normal patients achieved CR: 5 of 6 (83%) in group 1, and 3 of 5 (60%) in group 2. Five of 12 (42%) cytogenetically abnormal patients achieved CR. No difference in duration of survival (group 1, median = 4.6 months vs. group 2, median = 10.2 months; P = .93) was observed between the 2 groups. We conclude that AML‐M6 is typified by multilineage involvement of hematopoietic cells. The morphology of erythroblasts in patients with AML‐M6 may correlate with cytogenetic abnormalities and rate of CR. © 1995 Wiley‐Liss, Inc.
Neurobiology of Smooth Pursuit Eye Movement Deficits in Schizophrenia: An fMRI Study
Authors: Jason R. Tregellas, Jody L. Tanabe, David E. Miller, Randal G. Ross, Ann Olincy, Robert Freedman
Journal: American Journal of Psychiatry (2004)

Smooth pursuit eye movements are abnormal in patients with schizophrenia. The investigators used functional magnetic resonance imaging (fMRI) to compare brain hemodynamic response during a smooth pursuit eye movement task in patients with schizophrenia and healthy comparison subjects.Fourteen patients with schizophrenia and 14 healthy comparison subjects performed a smooth pursuit eye movement task while undergoing 1.5-T fMRI. Echo-planar images from the blocked design were evaluated with both a whole-brain random-effects analysis and a region-of-interest analysis. Smooth pursuit deficits were assessed outside the fMRI apparatus by using infrared oculography and were assessed during scanning by evaluating echo-planar time-series data from the eyes.Compared to the healthy subjects, the patients with schizophrenia exhibited greater activity in both posterior hippocampi and the right fusiform gyrus during smooth pursuit eye movements. The region-of-interest analysis revealed subtle activity deficits in frontal and occipital regions in the patients with schizophrenia. Smooth pursuit deficits in the subjects with schizophrenia included lower gain (eye velocity relative to target velocity) and a higher percentage of total eye movements due to anticipatory saccades, compared with the healthy subjects.The observed group differences are consistent with evidence for diminished inhibitory function in the hippocampus as well as for a disturbance in a frontotemporal network subserving smooth pursuit eye movements in schizophrenia.
Sarcoid pleural effusion: three cases and review of the literature.
Authors: A J Nicholls, J A Friend, J S Legge
Journal: Thorax (1980)

Pleural sarcoidosis is rare--it is little recognised in Birtian although several cases have been reported in the international literature. Three white men with pleural effusions caused by sacroidosis have been seen in a two-year period when approximately 60 new cases of thoracic sarcoidosis have been presented. In one patient a recurrent massive effusion was only diagnosed as being caused by sarcoidosis after thoractomy, and in two further patients small symptomatic pleural effusions were present at the onset of typical sarcoidosis. Two patients were successfully treated with steroids and the third improved spontaneously. Percutaneous biopsy is not always helpful in diagnosing pleural sarcoidosis, but a lymphocytic, often blood-stained, pleural aspirate is highly characteristic. While other diseases may coexist, a pleural effusion in a patient with histologically proven sarcoidosis is more likely to be caused by the primary disease than by any other condition.
Insulin resistance is associated with reduced fasting and insulin-stimulated glycogen synthase phosphatase activity in human skeletal muscle.
Authors: Y Kida, A Esposito-Del Puente, C Bogardus, D M Mott
Journal: Journal of Clinical Investigation (1990)

Insulin-stimulated glycogen synthase activity in human skeletal muscle correlates with insulin-mediated glucose disposal rate (M) and is reduced in insulin-resistant subjects. We have previously reported reduced insulin-stimulated glycogen synthase activity associated with reduced fasting glycogen synthase phosphatase activity in skeletal muscle of insulin-resistant Pima Indians. In this study we investigated the time course for insulin stimulation of glycogen synthase and synthase phosphatase during a 2-h high-dose insulin infusion (600 mU/min per m2) in six insulin-sensitive caucasians (group S) and in five insulin-resistant Pima Indians (group R). Percutaneous muscle biopsies were obtained from the quadriceps femoris muscle after insulin infusion for 0, 10, 20, 40, and 120 min. In group S, insulin-stimulated glycogen synthase activity increased with time and was significantly higher than in group R. In group S, synthase phosphatase activity increased significantly by 25% at 10 min and then decreased gradually. No significant change in synthase phosphatase was seen in group R and activity was lower than group S at 0 to 20 min. These data suggest that a low basal synthase phosphatase activity and a defect in its response to insulin explain, at least in part, reduced insulin stimulation of skeletal muscle glycogen synthase associated with insulin resistance.
Effective Suppression of Vascular Network Formation by Combination of Antibodies Blocking VEGFR Ligand Binding and Receptor Dimerization
Authors: Denis Tvorogov, Andrey Anisimov, Wei Zheng, Veli-Matti Leppänen, Tuomas Tammela, Simonas Laurinavicius, Wolfgang Holnthoner, Hanna Heloterä, Tanja Holopainen, Michael Jeltsch, Nisse Kalkkinen, Hilkka Lankinen, Päivi M. Ojala, Kari Alitalo
Journal: Cancer Cell (2010)
Early-stage Hodgkin's disease: Long-term results with radiotherapy alone or combined radiotherapy and chemotherapy
Authors: E. Brusamolino, M. Lazzarino, E. Orlandi, A. Canevari, E. Morra, G. Castelli, E.P. Alessandrino, G. Pagnucco, C. Astori, A. Livraghi, F. Corbella, P. Franchini, C. Bernasconi
Journal: Annals of Oncology (1994)
Monoamine oxidase-B (MAO-B) inhibitors: implications for disease-modification in Parkinson’s disease
Authors: Kay Cheong Teo, Shu-Leong Ho
Journal: Translational Neurodegeneration (2013)

There is a substantial amount of evidence from experimental parkinsonian models to show the neuroprotective effects of monoamine oxidase-B (MAOB) inhibitors. They have been studied for their potential disease-modifying effects in Parkinson's disease (PD) for over 20 years in various clinical trials. This review provides a summary of the clinical trials and discusses the implications of their results in the context of disease-modification in PD. Earlier clinical trials on selegiline were confounded by symptomatic effects of this drug. Later clinical trials on rasagiline using delayed-start design provide newer insights in disease-modification in PD but success in achieving the aims of this strategy remain elusive due to obstacles, some of which may be insurmountable.
Kissing Cousins, Arranged Marriages, and Genetic Diversity
Authors: Joseph Caspermeyer
Journal: Molecular Biology and Evolution (2015)

In the first study of its kind, Guillot et al. (2015) have examined the effects of arranged marriages on genetic diversity. From hemophilia and color blindness among British and Russian monarchies, people have long known the potential damaging genetic consequences of inbreeding. But until recently, no one could measure or understand the impact of marriage rules on genetic diversity. Among the traditional culture of the Indonesian Rindi, with an isolated population of just a few thousand on the island of Sumba, marriage rules dictate that a man ideally marries his first cousin on his mother’s side, with an aim to consolidate wealth and power by bringing the bride into his family’s sphere of social influence. Armed with new DNA sequencing data and a computer simulation tool called SMARTPOP, the team wanted to understand two key questions: 1) What are the expected genetic consequences of following the marriage rules? 2) From their genetic detective work, how closely do the Rindi actually follow the rules? According to the team’s simulations, the Rindi marriage rules should lead to a reduction in genetic diversity. But in a surprising result, their data show that the Rindi do not always strictly follow the rules, showing a relaxed compliance (long-term averages indicate two of three adhere to the rules, based on their analyses) that produced a genetic diversity similar to random mating. The authors conclude that, in the end, the Rindi marriage rules are treated with enough flexibility to form social connections without having a harmful effect on biological diversity. “People like to say they follow the rules, but actually we’re all really good at looking the other way if people don’t. Our work suggests that sometimes that’s a good thing,” Cox said. With SMARTPOP, the research team has developed a useful open-source tool for the research community to examine how other marriage rules throughout the world may affect human diversity.
Population Variation Revealed High-Altitude Adaptation of Tibetan Mastiffs
Authors: Yan Li, Dong-Dong Wu, Adam R. Boyko, Guo-Dong Wang, Shi-Fang Wu, David M. Irwin, Ya-Ping Zhang
Journal: Molecular Biology and Evolution (2014)

With the assistance of their human companions, dogs have dispersed into new environments during the expansion of human civilization. Tibetan Mastiff (TM), a native of the Tibetan Plateau, was derived from the domesticated Chinese native dog and, like Tibetans, has adapted to the extreme environment of high altitude. Here, we genotyped genome-wide single-nucleotide polymorphisms (SNPs) from 32 TMs and compared them with SNPs from 20 Chinese native dogs and 14 gray wolves (Canis lupus). We identified 16 genes with signals of positive selection in the TM, with 12 of these candidate genes associated with functions that have roles in adaptation to high-altitude adaptation, such as EPAS1, SIRT7, PLXNA4, and MAFG that have roles in responses to hypoxia. This study provides important information on the genetic diversity of the TM and potential mechanisms for adaptation to hypoxia.
Severe periodontal disease associated with severe rheumatoid arthritis is a predictive factor for clinical infliximab response
Authors: H Marotte, P Miossec, L Grange, B Pallot-Prades, P Gaudin, T Thomas
Journal: Annals of the Rheumatic Diseases (2012)

<h3>Background</h3> Prediction of tumour necrosis factor α (TNFα) response remains a huge challenge. Recently, a bad dental hygiene was described to be associated with a poor response to TNFα blockers in 20 rheumatoid arthritis (RA) patients. Previously, the authors reported an association between dental bone loss and joint damage in established 147 RA. Here, the authors investigated association between severe periodontal disease (PD) with or without joint damage and response to infliximab in RA patients. <h3>Methods</h3> All 101 RA patients enrolled in the study had typical clinical and biological features of severe RA. Their mean (SD) age was 50.6 (15.5) years. Patients were predominantly women (77.2%) with mean disease duration of 12.3 (9.8) years, and 81.2% were RF positive. Most patients had active disease with a disease activity score-28 (DAS28) at 5.1 (1.12) despite methotrexate treatment. They all were treated with infliximab according to the usual regimen in association with methotrexate. American College of Rheumatology 20 response was evaluated at 6 months and DAS28 improvement was calculated. Severe PD was defined by a periodontal bone destruction according to the Hugoson and Jordan criteria by an alveolar bone loss with a horizontal alveolysis over one third of the normal bone height. Joint damage was defined according to the Larsen wrist x-ray score with a right Larsen wrist score ≥2. χ2 test and non-parametric test were performed. <h3>Results</h3> Among our population, 62 patients had severe PD and 73 patients had joint damage. An association between severe PD and joint damage was observed (χ2 test=3.9; p&lt;0.05). However, only 48 patients had destruction at both wrist and periondotal sites while 16 had no destruction at these two sites; 23 had only wrist destruction; and 14 had only periodontal destruction. At 6 months, 71 patients reached the ACR20 response criteria. No association between PD severity or joint damage and ACR20 response was observed. Then, the authors compared DAS28 improvement according to PD severity. Likewise, DAS28 improvement was similar in RA patients with severe PD (median (25th–75th quartile)) at 1.85 (0.59–3.07)) compared to RA patients without severe PD (1.63 (1.01–2.68); not significant). Similarly, DAS28 improvement was equal according to the joint damage status (1.85 (1.05–3.11)) in RA patients with joint damage compared to RA patients without joint damage (1.53 (0.11–2.79); not significant). <h3>Conclusion</h3> These results suggested no association between severe periodontal disease and response to infliximab. RA severity markers are not predictor to infliximab response.
Incidence, Risk Factors, and Outcomes of Catheter-Related Thrombosis in Adult Patients With Cancer
Authors: Agnes Y.Y. Lee, Mark N. Levine, Gregory Butler, Carolyn Webb, Lorrie Costantini, Chushu Gu, Jim A. Julian
Journal: Journal of Clinical Oncology (2006)

Thrombosis of long-term central venous catheters (CVC) is a serious complication that causes morbidity and interrupts the infusion of chemotherapy, intravenous medication, and blood products. We performed a prospective study to examine the incidence, risk factors, and long-term complications of symptomatic catheter-related thrombosis (CRT) in adults with cancer. Consecutive patients with cancer, undergoing insertion of a CVC, were enrolled and prospectively followed while their catheter remained in place plus 4 subsequent weeks or a maximum of 52 weeks, whichever came first. Patients with symptomatic CRT were followed for an additional 52 weeks from the date of CRT diagnosis. The end points were symptomatic CRT, symptomatic pulmonary embolism (PE), postphlebitic syndrome, and catheter life span. Over 76,713 patient-days of follow-up, 19 of 444 patients (4.3%) had symptomatic CRT in 19 of 500 catheters (0.3 per 1,000 catheter-days). The median time to CRT was 30 days and the median catheter life span was 88 days. Significant baseline risk factors for CRT were: more than one insertion attempt (odds ratio [OR] = 5.5; 95% CI, 1.2 to 24.6; P = .03); ovarian cancer (OR = 4.8; 95% CI, 1.5 to 15.1; P = .01); and previous CVC insertion (OR = 3.8; 95% CI, 1.4 to 10.4; P = .01). Nine of the 19 CRT patients were treated with anticoagulants alone, eight patients were treated with anticoagulants and catheter removal, while two patients did not receive anticoagulation. None had recurrent CRT or symptomatic PE. Postphlebitic symptoms were infrequent. In adults with cancer, the incidence of symptomatic CRT is low and long-term complications are uncommon.