tbuckley/cabot-search huggingface dataset:
Incremental value of T-SPOT.<i>TB</i>for diagnosis of active pulmonary tuberculosis in children in a high-burden setting: a multivariable analysis
Authors: Daphne I Ling, Mark P Nicol, Madhukar Pai, Sandra Pienaar, Nandini Dendukuri, Heather J Zar
Journal: Thorax (2013)

<h3>Introduction</h3> Interferon γ release assays (IGRAs) are increasingly used for tuberculosis (TB) infection, but their incremental value beyond patient demographics, clinical signs and conventional tests for active disease has not been evaluated in children. <h3>Methods</h3> The incremental value of T-SPOT.<i>TB</i> was assessed in 491 smear-negative children from two hospitals in Cape Town, South Africa. Bayesian model averaging was used to select the optimal set of patient demographics and clinical signs for predicting culture-confirmed TB. The added value of T-SPOT.<i>TB</i> over and above patient characteristics and conventional tests was measured using statistics such as the difference in the area under the receiver operating characteristic curve (AUC), the net reclassification improvement (NRI) and the integrated discrimination improvement (IDI). <h3>Results</h3> Cough longer than 2 weeks, fever longer than 2 weeks, night sweats, malaise, history of household contact and HIV status were the most important predictors of culture-confirmed TB. Binary T-SPOT.<i>TB</i> results did not have incremental value when added to the baseline model with clinical predictors, chest radiography and the tuberculin skin test. The AUC difference was 3% (95% CI 0% to 7%). Using risk cut-offs of &lt;10%, 10–30% and &gt;30%, the NRI was 7% (95% CI −8% to 31%) but the CI included the null value. The IDI was 3% (95% CI 0% to 11%), meaning that the average predicted probability across all possible cut-offs improved marginally by 3%. <h3>Conclusions</h3> In a high-burden setting, the T-SPOT.<i>TB</i> did not have added value beyond clinical data and conventional tests for diagnosis of TB disease in smear-negative children.
MGMT and MLH1 promoter methylation versus APC, KRAS and BRAF gene mutations in colorectal cancer: indications for distinct pathways and sequence of events
Authors: S. de Vogel, M.P. Weijenberg, J.G. Herman, K.A.D. Wouters, A.F.P.M. de Goeij, P.A. van den Brandt, A.P. de Bruïne, M. van Engeland
Journal: Annals of Oncology (2009)
Deficiency of P62, a putative collagen receptor, in platelets from a patient with defective collagen‐induced platelet aggregation
Authors: Ryukichi Ryo, Akinori Yoshida, Wataru Sugano, Mutsumi Yasunaga, Katsuji Nakayama, Katsuyasu Saigo, Masashi Adachi, Nobuo Yamaguchi, Minoru Okuma
Journal: American Journal of Hematology (1992)

Abstract Recently, we described a platelet antibody against a putative collagen receptor (P62), which was found in a patient with idiopathic thrombocytopenic purpura (ITP) (Blood 69:1712). We now report a deficiency of the P62 receptor in a young man whose platelets showed defective collagen‐induced platelet aggregation. He had a mild bleeding tendency and slight thrombocytopenia. The results of coagulation and fibrinolysis studies were normal. The patient's platelets were partially unresponsive to collagen, although aggregation in response to ADP, thrombin, ristocetin, and calcium ionophore (A23187) was almost normal. Adhesion of his platelets to bovine collagen was markedly reduced. Addition of collagen caused no synthesis of thromboxane (TX)B 2 , in platelet rich plasma (PRP) from this patient. Furthermore, collagen produced no rise of cytosolic free calcium ([Ca 2+ ]i) in fura2‐loaded platelets. In contrast, thrombin caused TXB 2 , formation and an increase of [Ca 2+ ]i in his platelets. These results suggest defective interaction between the platelets and collagen. The lgG from the ITP‐patient induced irreversible aggregation in normal PRP, but caused no aggregation of the young man's platelets. Immunoblot studies showed that normal platelets had antigens with a molecular weight of 62 KDa under reducing conditions and of 57 KDa under nonreducing conditions. In contrast, the young man's platelets had no P62 band, although GPla/lla and thrombospondin were normally present. These results indicate that impaired collagen‐induced aggregation in the patient's platelets was due to a deficiency of P62 and confirm that P62 may play a crucial role as a collagen receptor in platelet activation.
A Type VI Secretion-Related Pathway in Bacteroidetes Mediates Interbacterial Antagonism
Authors: Alistair B. Russell, Aaron G. Wexler, Brittany N. Harding, John C. Whitney, Alan J. Bohn, Young Ah Goo, Bao Q. Tran, Natasha A. Barry, Hongjin Zheng, S. Brook Peterson, Seemay Chou, Tamir Gonen, David R. Goodlett, Andrew L. Goodman, Joseph D. Mougous
Journal: Cell Host & Microbe (2014)
Intrinsic misalignment in dialogue: Why there is no unique context in a conversation
Authors: Jonathan Ginzburg
Journal: Behavioral and Brain Sciences (2004)

Pickering & Garrod's (P&G's) claim that conversationalists do not explicitly keep track of their interlocuters' information states is important. Nonetheless, via alignment, they seem to create a virtually symmetrical view of the information states of speaker and addressee - a key component of their accounts of collaborative utterances and of self-monitoring. As I show, there is significant evidence for intrinsic contextual misalignment between conversationalists that can persist across turns.
Shedding new light on wood smoke: a risk factor for respiratory health
Authors: C. Boman, B. Forsberg, T. Sandström
Journal: European Respiratory Journal (2006)

The burning of wood is probably our oldest source for heating and cooking, and has been used by man for tens of thousands of years. Combustion of biomass, such as wood, animal dung and crop residues, is still used for cooking and heating by a large proportion of the global population, especially in less developed countries. In the industrialised world, and in countries with a cold winter climate, wood and other biomasses are widely used for heat production in residential wood log boilers, stoves and fireplaces. With the recognition of the limitations in amounts and durability of petroleum-based products, as well as an increasing concern regarding the issue of global warming, the interest in wood and other biomasses as alternative, sustainable and CO2-neutral energy sources for fuel production and heating has emerged.

In the present issue of the European Respiratory Journal , Orozco-Levi et al . 1 studied wood-smoke exposure and the risk of chronic obstructive pulmonary disease (COPD) in Spain. This contradicts the common assumption that “natural and biological materials” are generally friendly and harmless, as they have been in use since ancient times. Concerning the emissions from domestic wood and charcoal combustion, there is clearly a background of a large number of organic and inorganic components that may be associated with adverse biological events. The potential health effects of by-products, such as volatile organic …
Erlotinib Resistance in Lung Cancer Cells Mediated by Integrin β1/Src/Akt-Driven Bypass Signaling
Authors: Rina Kanda, Akihiko Kawahara, Kosuke Watari, Yuichi Murakami, Kahori Sonoda, Masashi Maeda, Hideaki Fujita, Masayoshi Kage, Hidetaka Uramoto, Carlota Costa, Michihiko Kuwano, Mayumi Ono
Journal: Cancer Research (2013)

Abstract EGF receptor (EGFR) kinase inhibitors, including gefitinib and erlotinib, exert potent therapeutic efficacy in non–small cell lung cancers harboring EGFR-activating mutations. However, most patients ultimately develop resistance to these drugs. Here, we report a novel mechanism of acquired resistance to EGFR tyrosine kinase inhibitors and the reversal of which could improve clinical outcomes. In erlotinib-resistant lung cancer cells harboring activating EGFR mutations that we established, there was increased expression of Src, integrin β1, α2, and α5 along with enhanced cell adhesion activity. Interestingly, RNAi-mediated silencing of integrin β1 restored erlotinib sensitivity and reduced activation of Src and Akt after erlotinib treatment. Furthermore, Src silencing inhibited Akt phosphorylation and cell growth, with this inhibitory effect further augmented by erlotinib treatment. Increased expression of integrin β1, α5, and/or α2 was also observed in refractory tumor samples from patients with lung cancer treated with erlotinib and/or gefitinib. Together, our findings identify the integrin β1/Src/Akt signaling pathway as a key mediator of acquired resistance to EGFR-targeted anticancer drugs. Cancer Res; 73(20); 6243–53. ©2013 AACR.
Narrative Review: Diseases That Masquerade as Infectious Cellulitis
Authors: Matthew E. Falagas, Paschalis I. Vergidis
Journal: Annals of Internal Medicine (2005)

For cellulitis that does not respond to conventional antimicrobial treatment, clinicians should consider, among other explanations, several noninfectious disorders that might masquerade as infectious cellulitis. Diseases that commonly masquerade as this condition include thrombophlebitis, contact dermatitis, insect stings, drug reactions, eosinophilic cellulitis (the Wells syndrome), gouty arthritis, carcinoma erysipelatoides, familial Mediterranean fever, and foreign-body reactions. Diseases that uncommonly masquerade as infectious cellulitis include urticaria, lymphedema, lupus erythematosus, sarcoidosis, lymphoma, leukemia, Paget disease, and panniculitis. Clinicians should do an initial diagnostic work-up directed by the findings from a detailed history and complete physical examination. In many cases, skin biopsy is the only tool that helps identify the correct diagnosis. Special tests may also be needed.
MID-TERM RESULTS OF AUTOLOGOUS MATRIX INDUCED CHONDROGENESIS (AMIC) IN CARTILAGE KNEE SURGERY
Authors: Ralf Oheim, Peter Behrens, Piero Volpi, Laura de Girolamo, Edgar Reiss Eric, Werner Zoch, Sven Anders, Justus Gille
Journal: British Journal of Sports Medicine (2013)

Introduction The regeneration capacity of articular cartilage is very limited. Therefore, cartilage defects heal poorly and are known as prearthrotic lesions. Autologous Matrix-Induced Chondrogenesis (AMIC) is an innovative treatment concept for localized full-thickness cartilage defects. This technique combines the well-established microfracturing with a collagen I/III scaffold fixated by fibrin glue. Methods Presented are medium-term results of two different prospective studies of patients treated with AMIC. Symptomatic full-thickness cartilage lesions (Outerbridge grade III or IV) were treated using AMIC (Chondro-Gide, Geistlich Pharma, Switzerland). Patients were initially evaluated by established knee scores (e.g. Lysholm score, IKDC score) and in selected cases by magnetic resonance imaging (MRI). Patients were re-evaluated up to 5 years after the initial procedure. Results In total 84 patients could be followed up. The average age of patients was in both groups 37 years (16–61 years). The mean defect size was 3.4 cm 2 respectively 4.2 cm 2 . The majority of patients were satisfied with the postoperative outcome, reporting a significant decrease of pain level. Significant improvement of the mean Lysholm score was observed as early as 1 year after AMIC and further increased values were noted up to two years postoperatively. MRI analysis showed moderate to complete filling with a normal to incidentally hyperintense signal in most cases. Conclusion AMIC is an effective and safe method of treating symptomatic full-thickness chondral defects of the knee in appropriately selected cases. However, further studies with long-term follow-up are needed to determine whether the grafted area will maintain structural and functional integrity over time. Level of evidence: Prognostic study, Level IV.
Depression and impotence
Authors: R P Snaith
Journal: BMJ (1994)

EDITOR, - For a long period erectile dysfunction (impotence) was assumed to have primarily a psychological basis. Except in cases of severe neurological impairment and endocrinopathies, the management of the disorder was handed to psychotherapists, marriage counsellors, or whoever else might be found to offer guidance. In the 1960s Masters and Johnson set out a view of the nature of sexually dysfunctional disorders together with a plan of treatment that was persuasive and partially successful1; they provided …
Selective use of diagnostic tests inpatients with syncope of unknown cause
Authors: Roberto Garcia-Civera, Ricardo Ruiz-Granell, Salvador Morell-Cabedo, Rafael Sanjuan-Mañez, Francisco Perez-Alcala, Eva Plancha, Alejandro Navarro, Segismundo Botella, Angel LLacer
Journal: Journal of the American College of Cardiology (2003)
A MicroRNA Cluster at 14q32 Drives Aggressive Lung Adenocarcinoma
Authors: Ernest Nadal, Jinjie Zhong, Jules Lin, Rishindra M. Reddy, Nithya Ramnath, Mark B. Orringer, Andrew C. Chang, David G. Beer, Guoan Chen
Journal: Clinical Cancer Research (2014)

Abstract Purpose: To determine whether different subtypes of lung adenocarcinoma (AC) have distinct microRNA (miRNA) expression profiles, and to identify miRNAs associated with aggressive subgroups of resected lung AC. Experimental Design: miRNA expression profile analysis was performed in 91 resected lung AC and 10 matched nonmalignant lung tissues using a PCR-based array. An independent cohort of 60 lung ACs was used for validating by quantitative PCR the top 3 prognostic miRNAs. Gene-expression data from 51 miRNA profiled tumors was used for determining transcript-specific miRNA correlations and gene-enrichment pathway analysis. Results: Unsupervised hierarchical clustering of 356 miRNAs identified 3 major clusters of lung AC correlated with stage (P = 0.023), tumor differentiation (P &amp;lt; 0.003), and IASLC histologic subtype of lung AC (P &amp;lt; 0.005). Patients classified in cluster 3 had worse survival as compared with the other clusters. Eleven of 22 miRNAs associated with poor survival were encoded in a large miRNA cluster at 14q32. The top 3 prognostic 14q32 miRNAs (miR-411, miR-370, and miR-376a) were validated in an independent cohort of 60 lung AC. A significant association with cell migration and cell adhesion was found by integrating gene-expression data with miR-411, miR-370, and miR-376a expression. miR-411 knockdown significantly reduced cell migration in lung AC cell lines and this miRNA was overexpressed in tumors from patients who relapsed systemically. Conclusions: Different morphologic subtypes of lung AC have distinct miRNA expression profiles, and 3 miRNAs encoded at 14q32 (miR-411, miR-370, and miR-376a) were associated with poor survival after lung AC resection. Clin Cancer Res; 20(12); 3107–17. ©2014 AACR.
Extranodal Marginal Zone B-Cell Lymphoma of Mucosa-Associated Lymphoid Tissue Type Developing in Gonarthritis Deformans
Authors: Jun-ichiro Ikeda, Eiichi Morii, Amane Yamauchi, Masaharu Kohara, Nobuyuki Hashimoto, Hideki Yoshikawa, Masafumi Iwasaki, Katsuyuki Aozasa
Journal: Journal of Clinical Oncology (2007)
CD4+CD25+ T Cells Regulate Virus-specific Primary and Memory CD8+ T Cell Responses
Authors: Susmit Suvas, Uday Kumaraguru, Christopher D. Pack, Sujin Lee, Barry T. Rouse
Journal: The Journal of Experimental Medicine (2003)

Naturally occurring CD4+CD25+ regulatory T cells appear important to prevent activation of autoreactive T cells. This article demonstrates that the magnitude of a CD8+ T cell-mediated immune response to an acute viral infection is also subject to control by CD4+CD25+ T regulatory cells (Treg). Accordingly, if natural Treg were depleted with specific anti-CD25 antibody before infection with HSV, the resultant CD8+ T cell response to the immunodominant peptide SSIEFARL was significantly enhanced. This was shown by several in vitro measures of CD8+ T cell reactivity and by assays that directly determine CD8+ T cell function, such as proliferation and cytotoxicity in vivo. The enhanced responsiveness in CD25-depleted animals was between three- and fourfold with the effect evident both in the acute and memory phases of the immune response. Surprisingly, HSV infection resulted in enhanced Treg function with such cells able to suppress CD8+ T cell responses to both viral and unrelated antigens. Our results are discussed both in term of how viral infection might temporarily diminish immunity to other infectious agents and their application to vaccines. Thus, controlling suppressor effects at the time of vaccination could result in more effective immunity.
Observer variation in the diagnosis of superficial oesophageal adenocarcinoma: another spanner in the works?
Authors: D Alderson
Journal: Gut (2002)

The distinction between high grade dysplasia and intramucosal carcinoma is not easily made by expert pathologists, with little improvement even after agreeing on uniform criteria for the use of

The rapidly rising incidence of oesophageal adenocarcinoma in the Western world has stimulated considerable experimental and clinical research in recent years. After a long period of uncertainty, it is now generally held that the majority, if not all, of these cancers arise on a background of intestinal metaplasia (Barrett’s oesophagus), secondary to chronic gastro-oesophageal reflux. While there has been much debate on the risk of cancer development, it is again accepted that in a proportion of patients, this metaplastic epithelium becomes unstable, leading to a sequential progression through dysplasia to carcinoma. Considerable effort has gone into characterising the changes which seem to occur at the molecular level 1.

In this issue, Ormsby and colleagues2 suggest that it may be important to distinguish high grade dysplasia (HGD) from intramucosal carcinoma (IMC) in order to reach a decision about endoscopic surveillance and how this might influence the nature and timing of subsequent therapy [see page 671]. They show that the distinction between HGD and IMC is not easily …
Inflatable hollow obturator prostheses for patients undergoing an extensive maxillectomy: a case report
Authors: Yue-Zhong Hou, Zhi Huang, Hong-Qiang Ye, Yong-Sheng Zhou
Journal: International Journal of Oral Science (2012)

The presence of a large palatal or maxillary defect after partial or total maxillectomy for tumor, trauma or congenital deformation poses a challenge to prosthodontists, particularly when the use of an implant cannot be considered. This case report described the use of an air valve in a hollow silicone obturator to manufacture an inflatable obturator that could be extended further into undercut area to retain itself. The inflatable obturator exhibited adequate retention, stability and border sealing, thereby improving the masticatory,pronunciation and swallowing functions of patients. It may be a suitable alternative treatment option to an implant-retained obturator.
Genetic Variation in NCAM1 Contributes to Left Ventricular Wall Thickness in Hypertensive Families
Authors: Donna K. Arnett, Kristin J. Meyers, Richard B. Devereux, Hemant K. Tiwari, Charles C. Gu, Laura K. Vaughan, Rodney T. Perry, Amit Patki, Steven A. Claas, Yan V. Sun, Ulrich Broeckel, Sharon L. Kardia
Journal: Circulation Research (2011)

Left ventricular (LV) mass and related phenotypes are heritable, important predictors of cardiovascular disease, particularly in hypertensive individuals.Identify genetic predictors of echocardiographic phenotypes in hypertensive families.A multistage genome-wide association study (GWAS) was conducted in hypertensive-ascertained black families (HyperGEN, stage I; GENOA, stage II); findings were replicated in HyperGEN white families (stage III). Echocardiograms were collected using a common protocol, and participants were genotyped with the Affymetrix Genome-Wide Human SNP 6.0 Array. The following were analyzed using mixed models adjusted for ancestry: in stages I and II, 1258 and 989 blacks, respectively; and in stage III, 1316 whites. Phenotypes included LV mass, LV internal dimension (LVID), wall thicknesses (posterior [PWT] and intraventricular septum [IVST]), and relative wall thickness (RWT). In stage I, 5 single nucleotide polymorphisms (SNPs) had P≤10(-6). In stage II, 1 SNP (rs1436109; NCAM1 intron 1) replicated with the same phenotype (PWT, P=0.025) in addition to RWT (P=0.032). In stage III, rs1436109 was associated with RWT (P=5.47×10(-4)) and LVID (P=1.86×10(-4)). Fisher combined probability value for all stages was RWT=3.80×10(-9), PWT=3.12×10(-7), IVST=8.69×10(-7), LV mass=2.52×10(-3), and LVID=4.80×10(-4).This GWAS conducted in hypertensive families identified a variant in NCAM1 associated with LV wall thickness and RWT. NCAM is upregulated during the remodeling period of hypertrophy to heart failure in Dahl salt-sensitive rats. Our initial screening in hypertensive blacks may have provided the context for this novel locus.
Co-targeting of convergent nucleotide biosynthetic pathways for leukemia eradication
Authors: David A. Nathanson, Amanda L. Armijo, Michelle Tom, Zheng Li, Elizabeth Dimitrova, Wayne R. Austin, Julian Nomme, Dean O. Campbell, Lisa Ta, Thuc M. Le, Jason T. Lee, Ryan Darvish, Ari Gordin, Liu Wei, Hsiang-I Liao, Moses Wilks, Colette Martin, Saman Sadeghi, Jennifer M. Murphy, Nidal Boulos, Michael E. Phelps, Kym F. Faull, Harvey R. Herschman, Michael E. Jung, Johannes Czernin, Arnon Lavie, Caius G. Radu
Journal: The Journal of Experimental Medicine (2014)

Pharmacological targeting of metabolic processes in cancer must overcome redundancy in biosynthetic pathways. Deoxycytidine (dC) triphosphate (dCTP) can be produced both by the de novo pathway (DNP) and by the nucleoside salvage pathway (NSP). However, the role of the NSP in dCTP production and DNA synthesis in cancer cells is currently not well understood. We show that acute lymphoblastic leukemia (ALL) cells avoid lethal replication stress after thymidine (dT)-induced inhibition of DNP dCTP synthesis by switching to NSP-mediated dCTP production. The metabolic switch in dCTP production triggered by DNP inhibition is accompanied by NSP up-regulation and can be prevented using DI-39, a new high-affinity small-molecule inhibitor of the NSP rate-limiting enzyme dC kinase (dCK). Positron emission tomography (PET) imaging was useful for following both the duration and degree of dCK inhibition by DI-39 treatment in vivo, thus providing a companion pharmacodynamic biomarker. Pharmacological co-targeting of the DNP with dT and the NSP with DI-39 was efficacious against ALL models in mice, without detectable host toxicity. These findings advance our understanding of nucleotide metabolism in leukemic cells, and identify dCTP biosynthesis as a potential new therapeutic target for metabolic interventions in ALL and possibly other hematological malignancies.