tbuckley/cabot-search huggingface dataset:
Tuberculosis comorbidity with communicable and non-communicable diseases: integrating health services and control efforts
Authors: Ben J Marais, Knut Lönnroth, Stephen D Lawn, Giovanni Battista Migliori, Peter Mwaba, Philippe Glaziou, Matthew Bates, Ruth Colagiuri, Lynn Zijenah, Soumya Swaminathan, Ziad A Memish, Michel Pletschette, Michael Hoelscher, Ibrahim Abubakar, Rumina Hasan, Afia Zafar, Guiseppe Pantaleo, Gill Craig, Peter Kim, Markus Maeurer, Marco Schito, Alimuddin Zumla
Journal: The Lancet Infectious Diseases (2013)

Recent data for the global burden of disease reflect major demographic and lifestyle changes, leading to a rise in non-communicable diseases. Most countries with high levels of tuberculosis face a large comorbidity burden from both non-communicable and communicable diseases. Traditional disease-specific approaches typically fail to recognise common features and potential synergies in integration of care, management, and control of non-communicable and communicable diseases. In resource-limited countries, the need to tackle a broader range of overlapping comorbid diseases is growing. Tuberculosis and HIV/AIDS persist as global emergencies. The lethal interaction between tuberculosis and HIV coinfection in adults, children, and pregnant women in sub-Saharan Africa exemplifies the need for well integrated approaches to disease management and control. Furthermore, links between diabetes mellitus, smoking, alcoholism, chronic lung diseases, cancer, immunosuppressive treatment, malnutrition, and tuberculosis are well recognised. Here, we focus on interactions, synergies, and challenges of integration of tuberculosis care with management strategies for non-communicable and communicable diseases without eroding the functionality of existing national programmes for tuberculosis. The need for sustained and increased funding for these initiatives is greater than ever and requires increased political and funder commitment.
Atrial natriuretic peptide inhibits growth of hepatoblastoma (HEP G2) cells by means of activation of clearance receptors
Authors: Hani M. Rashed, Hui Sun, Tarun B. Patel
Journal: Hepatology (1993)

To investigate whether atrial natriuretic factor regulates the growth of hepatocytes and to determine the receptor subtype involved in such modulation, we studied the effect of atrial natriuretic factor 103-126 and clearance receptor binding analogs of atrial natriuretic factor, (des-(Q 116 , S 117 , G 118 , L 119 , G 120 ) atrial natriuretic factor 102-121 and des-(C 105,121 ) atrial natriuretic factor 104-126) on growth of human hepatoblastoma cells. Atrial natriuretic factor 103-126 and des-(Q 116 , S 117 , G 118 , L 119 , G 120 ) atrial natriuretic factor 102-121 inhibited thymidine incorporation into human hepatoblastoma cells cultured in the presence of bovine serum albumin and epidermal growth factor but not in cells cultured in bovine serum albumin alone. Moreover, atrial natriuretic factor 103-126, des-(Q 116 , S 117 , G 118 , L 119 , G 120 ) atrial natriuretic factor 102-121 and des-(C 105,121 ) atrial natriuretic factor 104-126, in a concentration-dependent manner, inhibited thymidine incorporation and cell proliferation. As monitored by the ability of des-(Q 116 , S 117 , G 118 , L 119 , G 120 ) atrial natriuretic factor 102-121 to displace 125 I-labeled atrial natriuretic factor, epidermal growth factor increased the expression of cell surface clearance receptors. Epidermal growth factor also transiently increased the cellular content of atrial natriuretic factor clearance receptor messenger RNA without altering the levels of guanylyl cyclase-linked atrial natriuretic factor receptor messenger RNA levels. Maximal increase in atrial natriuretic factor clearance receptor messenger RNA coincided with the maximal increase in des-(Q 116 , S 117 , G 118 , L 119 , G 120 ) atrial natriuretic factor 102-121-displaceable 125 I-atrial natriuretic factor binding sites. The ability of atrial natriuretic factor clearance receptor-binding ligands to inhibit thymidine incorporation and cell proliferation-coupled with the selective upregulation of clearance receptor expression by epidermal growth factor, which facilitates the growth modulatory actions of atriopeptins-indicates that the atrial natriuretic factor clearance receptors mediate the growth regulatory actions of atrial natriuretic factor. Additionally, the clearance receptor-binding ligands decreased cellular cyclic AMP content only under conditions in which clearance receptors are expressed, suggesting that modulation of cyclic AMP by activation of these receptors regulates growth. (Hepatology 1993;17:677-684.)
Single-cell analysis reveals key roles for Bcl11a in regulating stem cell fate decisions
Authors: Ashley N Powers, Rahul Satija
Journal: Genome biology (2015)

Cell-cycle fluctuations drive significant transcriptomic heterogeneity in murine hematopoietic stem cells. Additionally, deletion of Bcl11a alters the regulation of hematopoietic stem cell quiescence, self-renewal, and fate choice. Please see related Research article: http://www.genomebiology.com/2015/16/1/178
Somatic generation of hybrid antibody H chain genes in transgenic mice via interchromosomal gene conversion.
Authors: A M Giusti, T Manser
Journal: The Journal of Experimental Medicine (1994)

We have constructed lines of mice with transgenes containing an antibody heavy (H) chain variable region (VHDJH) gene and various amounts of natural immunoglobulin (Ig) and plasmid flanking DNA. In these lines, recombination of the transgene and the endogenous Igh locus takes place in B cells, leading to the expression of functional H chains partially encoded by the transgenic VHDJH gene. Here, we demonstrate that the transgenic VHDJH gene, and various amounts of flanking sequence are recombined with Igh locus DNA via interchromosomal gene conversion. The structures of the resulting "hybrid" transgene-Igh H chain loci are consistent with the 3' end of the conversion occurring in regions of sequence identity, and the 5' end taking place between regions of little or no homology. This mode of antibody transgene recombination with the Igh locus is fundamentally different from the previously reported "trans H chain class switching" that results in reciprocal translocations. In contrast, this recombination resembles events previously observed in mammalian tissue culture cells between adjacent homologous chromosomal sequences, or transfected DNA and a homologous chromosomal target. Our data indicate that this recombination takes place at a low frequency, and that the frequency is influenced by both the length and extent of homology between the transgene and the Igh locus, but is not greatly affected by transgene copy number. This recombination pathway provides a novel approach for the subtle alteration of the clonal composition of the mouse B cell compartment in vivo using VH genes with defined structures and functions.
Practice Guidelines for Treatment of Peptic Ulcer Disease
Authors: M. Brian Fennerty
Journal: JAMA (1996)

To the Editor.  —Dr Soll and colleagues 1 acknowledge that treatment regimens for peptic ulcer disease remain cumbersome and recognize the need for more data from rigorous controlled trials; I am in total agreement. However, they follow this statement by mentioning that 3 regimens (a bismuth-based triple-therapy regimen, a proton pump inhibitor [PPI], and a PPI with 2 of these antibiotics: clarithromycin, metronidazole, or amoxicillin), out of the many described in the literature, are cautiously recommended. To my knowledge, there are no controlled prospective trials of US patients on which to base this recommendation. Furthermore, there are no community-based studies looking at the effectiveness of any single regimen.  It is further stated that the combination of ranitidine bismuth subcitrate and clarithromycin, despite having received approval by the Food and Drug Administration (FDA), should not be used without the addition of tetracycline or amoxicillin. I am unaware of any such data suggesting
Incidence of paramalignant disorders in bronchogenic carcinoma.
Authors: J W Rassam, G Anderson
Journal: Thorax (1975)

The incidence of paramalignant disorders was studied in 280 consecutive patients with early lung cancer confirmed histologically. The commonest disorders were weight loss exceeding 6.4 kg (30.7 percent of the series), finger clubbing (29 percent), fever (21.1 percent), and endocrinopathies (12.1 percent). Paramalignant diseases are common even in early lung cancer and all patients should have investigations for their detection.
Autoantibodies as biomarkers for the prediction of neuropsychiatric events in systemic lupus erythematosus
Authors: J G Hanly, M B Urowitz, L Su, S-C Bae, C Gordon, A Clarke, S Bernatsky, A Vasudevan, D Isenberg, A Rahman, D J Wallace, P R Fortin, D Gladman, J Romero-Dirz, J Sanchez-Guerrero, M A Dooley, I Bruce, K Steinsson, M Khamashta, S Manzi, R Ramsey-Goldman, G Sturfelt, O Nived, R van Vollenhoven, M Ramos-Casals, C Aranow, M Mackay, K Kalunian, G S Alarcón, B J Fessler, G Ruiz-Irastorza, M Petri, S Lim, D Kamen, C Peschken, V Farewell, K Thompson, C Theriault, J T Merrill
Journal: Annals of the Rheumatic Diseases (2011)

Objective Neuropsychiatric events occur unpredictably in systemic lupus erythematosus (SLE) and most biomarker associations remain to be prospectively validated. This study examined a disease inception cohort of 1047 SLE patients to determine which autoantibodies at enrolment predicted subsequent neuropsychiatric events. Methods Patients with a recent SLE diagnosis were assessed prospectively for up to 10 years for neuropsychiatric events using the American College of Rheumatology case definitions. Decision rules of graded stringency determined whether neuropsychiatric events were attributable to SLE. Associations between the first neuropsychiatric event and baseline autoantibodies (lupus anticoagulant (LA), anticardiolipin, anti-β 2 glycoprotein-I, anti-ribosomal P and anti-NR2 glutamate receptor) were tested by Cox proportional hazards regression. Results Disease duration at enrolment was 5.4±4.2 months, follow-up was 3.6±2.6 years. Patients were 89.1% female with mean (±SD) age 35.2±13.7 years. 495/1047 (47.3%) developed one or more neuropsychiatric event (total 917 events). Neuropsychiatric events attributed to SLE were 15.4% (model A) and 28.2% (model B). At enrolment 21.9% of patients had LA, 13.4% anticardiolipin, 15.1% anti-β 2 glycoprotein-I, 9.2% anti-ribosomal P and 13.7% anti-NR2 antibodies. LA at baseline was associated with subsequent intracranial thrombosis (total n=22) attributed to SLE (model B) (HR 2.54, 95% CI 1.08 to 5.94). Anti-ribosomal P antibody was associated with subsequent psychosis (total n=14) attributed to SLE (model B) (HR 3.92, 95% CI 1.23 to 12.5, p=0.02). Other autoantibodies did not predict neuropsychiatric events. Conclusion In a prospective study of 1047 recently diagnosed SLE patients, LA and anti-ribosomal P antibodies are associated with an increased future risk of intracranial thrombosis and lupus psychosis, respectively.
Creating Healthy Food and Eating Environments: Policy and Environmental Approaches
Authors: Mary Story, Karen M. Kaphingst, Ramona Robinson-O'Brien, Karen Glanz
Journal: Annual Review of Public Health (2007)

Food and eating environments likely contribute to the increasing epidemic of obesity and chronic diseases, over and above individual factors such as knowledge, skills, and motivation. Environmental and policy interventions may be among the most effective strategies for creating population-wide improvements in eating. This review describes an ecological framework for conceptualizing the many food environments and conditions that influence food choices, with an emphasis on current knowledge regarding the home, child care, school, work site, retail store, and restaurant settings. Important issues of disparities in food access for low-income and minority groups and macrolevel issues are also reviewed. The status of measurement and evaluation of nutrition environments and the need for action to improve health are highlighted.
Cerebral metastases (CM) in breast cancer (BC) with focus on triple-negative tumors
Authors: F. Heitz, P. Harter, A. Traut, H. J. Lueck, B. Beutel, A. du Bois
Journal: Journal of Clinical Oncology (2008)

1010 Background: We analysed the impact of a specific biologic subtype— triple-negative breast cancer (TN-BC)—characterized by lacking expression of steroid receptors and Her2neu (ER-/PR-/Her2neu-) on the occurrence of CM. Methods: Retrospective analysis of in 3,193 BC pts. treated consecutively between 1989 and 2006 in our EUSOMA breast unit. All pts. developing CM were included. Results: 338 pts. suffered from TN-BC (10.58%) and 80 pts. (2.5%) developed CM within a median observation period of 51 months (mos). 19 pts (23.75%) of all pts with CM had TN-BC and 5,6% of all pts with TN-BC had CM. Multivariate analysis indicated the highest risk for developing CM for TN-BC compared with all other types of BC (OR:4.16; 95%CI:2.26–7.64; p<0.001). Further independent risk factors were: ER-/PR-/Her2neu+ (OR:3.43; 95%CI:1.46–8.05; p=0.005), age ≤ 50 years (OR:2.02; 95%CI:1.17–3.49; p=0.012), UICC-stages III/IV (OR:2.49; 95%CI:1.19–5.22; p=0,016) and positive nodal-status (OR:2.37; 95%CI:1.10- 5.10; p=0.028). In addition, TN-BC showed inferior PFS and OS with 23 and 31.5 mos compared to 49.5 and 72 mos in other BC types (PFS:OR:3.2; 95%CI:2.1–18.1; p<0.0001/OS:OR 3.3;95%CI:2.7–18.8; p<0.0001), respectively. The median interval between primary diagnosis and occurrence of CM was 22 mos in TN- BC and 51 mos in other BC (OR:2.7; 95%CI:2.4–11.4; p<0.0001). OS after occurrence of CM was 4 mos in TN-BC and 8 mos on other BC, this trend was not significant. Conclusions: Patients with TN-BC have a higher risk for developing CM compared to other types of BC. This adds to a generally poorer prognosis in these pts. Even in pts. with CM, TN-BC represent a poor prognostic subgroup and CM occurred earlier and showed a trend for poorer outcome. Specific treatment regimens for this poor prognostic subgroup are warranted. Furthermore, the relative high incidence of CM in TN-BC questions if extended diagnostics (e.g. routine CNS MRI) should be applied to these pts. No significant financial relationships to disclose.
EphA2 Expression Is a Key Driver of Migration and Invasion and a Poor Prognostic Marker in Colorectal Cancer
Authors: Philip D. Dunne, Sonali Dasgupta, Jaine K. Blayney, Darragh G. McArt, Keara L. Redmond, Jessica-Anne Weir, Conor A. Bradley, Takehiko Sasazuki, Senji Shirasawa, Tingting Wang, Supriya Srivastava, Chee Wee Ong, Ken Arthur, Manuel Salto-Tellez, Richard H. Wilson, Patrick G. Johnston, Sandra Van Schaeybroeck
Journal: Clinical Cancer Research (2015)

EphA2, a member of the Eph receptor tyrosine kinases family, is an important regulator of tumor initiation, neovascularization, and metastasis in a wide range of epithelial and mesenchymal cancers; however, its role in colorectal cancer recurrence and progression is unclear.EphA2 expression was determined by immunohistochemistry in stage II/III colorectal tumors (N = 338), and findings correlated with clinical outcome. The correlation between EphA2 expression and stem cell markers CD44 and Lgr5 was examined. The role of EphA2 in migration/invasion was assessed using a panel of KRAS wild-type (WT) and mutant (MT) parental and invasive colorectal cancer cell line models.Colorectal tumors displayed significantly higher expression levels of EphA2 compared with matched normal tissue, which positively correlated with high CD44 and Lgr5 expression levels. Moreover, high EphA2 mRNA and protein expression were found to be associated with poor overall survival in stage II/III colorectal cancer tissues, in both univariate and multivariate analyses. Preclinically, we found that EphA2 was highly expressed in KRASMT colorectal cancer cells and that EphA2 levels are regulated by the KRAS-driven MAPK and RalGDS-RalA pathways. Moreover, EphA2 levels were elevated in several invasive daughter cell lines, and downregulation of EphA2 using RNAi or recombinant EFNA1 suppressed migration and invasion of KRASMT colorectal cancer cells.These data show that EpHA2 is a poor prognostic marker in stage II/III colorectal cancer, which may be due to its ability to promote cell migration and invasion, providing support for the further investigation of EphA2 as a novel prognostic biomarker and therapeutic target.
Colocalization of F-actin and talin during Fc receptor-mediated phagocytosis in mouse macrophages.
Authors: S Greenberg, K Burridge, S C Silverstein
Journal: The Journal of Experimental Medicine (1990)

We have studied the distribution of talin in J774 cells and mouse peritoneal macrophages undergoing Fc receptor-mediated phagocytosis. At early stages of phagocytosis, talin accumulates in the cells' cortical cytoplasm adjacent to the forming phagosome and extends into pseudopods that are encircling the particle. Talin colocalizes with F-actin at these sites. After particle ingestion is completed, F-actin and talin are no longer concentrated adjacent to phagosomes. Thus, talin and F-actin undergo dynamic and coordinate changes in their cytoplasmic location during Fc receptor-mediated phagocytosis.
Phase II Trial of a Transplantation Regimen of Yttrium-90 Ibritumomab Tiuxetan and High-Dose Chemotherapy in Patients With Non-Hodgkin's Lymphoma
Authors: Amrita Krishnan, Auayporn Nademanee, Henry C. Fung, Andrew A. Raubitschek, Arturo Molina, Dave Yamauchi, Roberto Rodriguez, Ricardo T. Spielberger, Peter Falk, Joycelynne M. Palmer, Stephen J. Forman
Journal: Journal of Clinical Oncology (2007)

Purpose This phase II trial evaluated the safety and efficacy of combining yttrium-90 ( 90 Y) ibritumomab tiuxetan with high-dose carmustine, cytarabine, etoposide, and melphalan (BEAM) and autologous stem-cell transplantation in patients with non-Hodgkin's lymphoma who were considered ineligible for total-body irradiation because of older age or prior radiotherapy. Patients and Methods Between May 2002 and January 2006, 14 days before autologous stem-cell transplantation, 41 patients with non-Hodgkin's lymphoma received standard-dose 90 Y ibritumomab tiuxetan (14.8 MBq/kg [0.4 mCi/kg]) followed by high-dose BEAM. Results The median age was 60 years (range, 19 to 78 years), and the median number of previous therapies was two (range, one to six). Disease histologies were diffuse large B-cell (n = 20), mantle cell (n = 13), follicular (n = 4), and transformed lymphoma (n = 4). With a median follow-up of 18.4 months (range, 5.5 to 53.3 months) the estimated 2-year overall and progression-free survival were 88.9% (95% CI, 75.3% to 95.2%) and 69.8% (95% CI, 56.4% to 79.7%). The median time to WBC engraftment was 11 days (range, 9 to 26 days) and time to platelet engraftment was 12 days (range, 3 to 107 days). Adverse events were similar to those seen historically with high-dose BEAM alone, and included grade 3 or 4 pulmonary toxicity in 10 patients. Conclusion Adding 90 Y ibritumomab tiuxetan to high-dose BEAM with autologous stem-cell transplantation is feasible and has a toxicity and tolerability profile similar to that observed with BEAM alone. Rates of progression-free survival seen in these patients are promising and warrant additional study.
SCN5A Mutations Associate With Arrhythmic Dilated Cardiomyopathy and Commonly Localize to the Voltage-Sensing Mechanism
Authors: William P. McNair, Gianfranco Sinagra, Matthew R.G. Taylor, Andrea Di Lenarda, Debra A. Ferguson, Ernesto E. Salcedo, Dobromir Slavov, Xiao Zhu, John H. Caldwell, Luisa Mestroni
Journal: Journal of the American College of Cardiology (2011)
When Is It Appropriate to Order an Ionized Calcium?
Authors: Laura M. Calvi, David A. Bushinsky
Journal: Journal of the American Society of Nephrology (2008)

Convincing evidence demonstrates that ionized calcium and not total calcium is the physiologically relevant component of blood calcium. Direct measurement of ionized calcium, however, is limited by difficulties in accurate analysis, lack of standardization, and need for special handling, all resulting in increased cost; therefore, strategies have been developed to estimate ionized calcium from total calcium adjusted for levels of albumin, measurements that are more available and relatively inexpensive. This commentary compares the advantages and limitations of direct or calculated determinations of ionized calcium. Also examined are available data illustrating the settings in which measurement of ionized calcium is preferred and, in some cases, necessary for clinical decision-making.
Added Value of Soluble Tumor Necrosis Factor-α Receptor 1 as a Biomarker of ESRD Risk in Patients With Type 1 Diabetes
Authors: Carol Forsblom, John Moran, Valma Harjutsalo, Tony Loughman, Johan Wadén, Nina Tolonen, Lena Thorn, Markku Saraheimo, Daniel Gordin, Per-Henrik Groop, Merlin C. Thomas
Journal: Diabetes Care (2014)

Recent studies have suggested that circulating levels of the tumor necrosis factor-α receptor 1 (sTNFαR1) may be a useful predictor for the risk of end-stage renal disease (ESRD) in patients with diabetes. However, its potential utility as a biomarker has not been formally quantified.Circulating levels of sTNFαR1 were assessed in 429 patients with type 1 diabetes and overt nephropathy from the Finnish Diabetic Nephropathy (FinnDiane) cohort study. Predictors of incident ESRD over a median of 9.4 years of follow-up were determined by Cox regression and Fine-Gray competing risk analyses. The added value of sTNFαR1 was estimated via time-dependent receiver operating characteristic curves, net reclassification index (NRI), and integrated discrimination improvement (IDI) for survival data.A total of 130 individuals developed ESRD (28%; ESRD incidence rate of 3.4% per year). In cause-specific modeling, after adjusting for baseline renal status, predictors of increased incidence of ESRD in patients with overt nephropathy were an elevated HbA1c, shorter duration of diabetes, and circulating levels of sTNFαR1. Notably, sTNFαR1 outperformed estimated glomerular filtration rate in terms of R(2). Circulating levels of the sTNFαR1 also remained associated with ESRD after adjusting for the competing risk of death. A prediction model including sTNFαR1 (as a -0.5 fractional polynomial) was superior to a model without it, as demonstrated by better global fit, an increment of R(2), the C index, and area under the curve. Estimates of IDI and NRI(>0) were 0.22 (95% CI 0.16-0.28; P < 0.0001) and 0.98 (0.78-1.23; P < 0.0001), respectively. The median increment in the risk score after including sTNFαR1 in the prediction model was 0.18 (0.12-0.30; P < 0.0001).Circulating levels of sTNFαR1 are independently associated with the cumulative incidence of ESRD. This association is both significant and biologically plausible and appears to provide added value as a biomarker, based on the absolute values of NRI and IDI.