tbuckley/cabot-search huggingface dataset:
Using comparative genomics to reorder the human genome sequence into a virtual sheep genome
Authors: Brian P Dalrymple, Ewen F Kirkness, Mikhail Nefedov, Sean McWilliam, Abhirami Ratnakumar, Wes Barris, Shaying Zhao, Jyoti Shetty, Jillian F Maddox, Margaret O'Grady, Frank Nicholas, Allan M Crawford, Tim Smith, Pieter J de Jong, John McEwan, V Hutton Oddy, Noelle E Cockett
Journal: Genome biology (2007)

Is it possible to construct an accurate and detailed subgene-level map of a genome using bacterial artificial chromosome (BAC) end sequences, a sparse marker map, and the sequences of other genomes? A sheep BAC library, CHORI-243, was constructed and the BAC end sequences were determined and mapped with high sensitivity and low specificity onto the frameworks of the human, dog, and cow genomes. To maximize genome coverage, the coordinates of all BAC end sequence hits to the cow and dog genomes were also converted to the equivalent human genome coordinates. The 84,624 sheep BACs (about 5.4-fold genome coverage) with paired ends in the correct orientation (tail-to-tail) and spacing, combined with information from sheep BAC comparative genome contigs (CGCs) built separately on the dog and cow genomes, were used to construct 1,172 sheep BAC-CGCs, covering 91.2% of the human genome. Clustered non-tail-to-tail and outsize BACs located close to the ends of many BAC-CGCs linked BAC-CGCs covering about 70% of the genome to at least one other BAC-CGC on the same chromosome. Using the BAC-CGCs, the intrachromosomal and interchromosomal BAC-CGC linkage information, human/cow and vertebrate synteny, and the sheep marker map, a virtual sheep genome was constructed. To identify BACs potentially located in gaps between BAC-CGCs, an additional set of 55,668 sheep BACs were positioned on the sheep genome with lower confidence. A coordinate conversion process allowed us to transfer human genes and other genome features to the virtual sheep genome to display on a sheep genome browser. We demonstrate that limited sequencing of BACs combined with positioning on a well assembled genome and integrating locations from other less well assembled genomes can yield extensive, detailed subgene-level maps of mammalian genomes, for which genomic resources are currently limited.
Standards of Reporting for MRI-targeted Biopsy Studies (START) of the Prostate: Recommendations from an International Working Group
Authors: Caroline M. Moore, Veeru Kasivisvanathan, Scott Eggener, Mark Emberton, Jurgen J. Fütterer, Inderbir S. Gill, Robert L. Grubb III, Boris Hadaschik, Laurence Klotz, Daniel J.A. Margolis, Leonard S. Marks, Jonathan Melamed, Aytekin Oto, Suzanne L. Palmer, Peter Pinto, Philippe Puech, Shonit Punwani, Andrew B. Rosenkrantz, Ivo G. Schoots, Richard Simon, Samir S. Taneja, Baris Turkbey, Osamu Ukimura, Jan van der Meulen, Arnauld Villers, Yuji Watanabe
Journal: European Urology (2013)
Sporadic fundic gland polyps and proximal polyposis associated with gastric adenocarcinoma share a common antral G cell hyperplasia
Authors: Paolo Declich, Gloria Silvia Arrigoni, Barbara Omazzi, Massimo Devani, Enrico Tavani, Alessandro Sioli, Stefano Bellone, Claudio Gozzini, Aurora Bortoli, Alberto Prada
Journal: Gut (2013)

We read with great interest the article by Worthley et al 1 that recently appeared in your Journal, and the subsequent letter on the same subject.2 We would like to make some comments on this interesting topic.

Worthley et al reported a new autosomal dominant syndrome that they named gastric adenocarcinoma and proximal polyposis of the stomach (GAPPS). GAPPS appears to be characterised by proximal gastric polyposis, particularly of the fundic gland type that often displays low and high grade dysplasia with early development of gastric cancer. These patients showed no evidence of colonic polyps, and other genetic syndromes were excluded. Yanaru-Fujisawa et al reported a further family with GAPPS.

So far, dysplasia has been described …
What Is the Contemporary Role of Radiofrequency Ablation in the Management of Small Renal Masses? Are Small Lesions the Radiologist's Tumors?
Authors: Maciej Salagierski, Bülent Akdogan, Sabine Brookman-May, Barbara Dobrowolska-Glazar, Vincenzo Ficarra, Johan F. Langenhuijsen, Martin Marszalek, Andrea Minervini, Oscar Rodriguez-Faba, Marco Roscigno, Alkuin Vandromme, Alessandro Volpe, Steven Joniau
Journal: European Urology (2012)
Triple-negative breast cancer: epidemiological considerations and recommendations
Authors: P. Boyle
Journal: Annals of Oncology (2012)

<h2>ABSTRACT</h2> Breast cancer is a major problem for global public health. Breast Cancer is the most common incident form of cancer in women around the world. The incidence is increasing while mortality is declining in many high-income countries. The last decade has seen a revolution in the understanding of breast cancer, with new classifications proposed that have significant prognostic value and provide guides to treatment options. Breast cancers that demonstrate the absence of oestrogen receptor and progesterone receptor and no overexpression of human epidermal growth factor receptor 2 (HER2) are referred to as triple-negative breast cancer (TNBC). There is now evidence emerging from epidemiological studies regarding important characteristics of this group of tumours that carry a relatively poorer prognosis than the major breast cancer sub-types. From this review of available data and information, there are some consistent findings that emerge. Women with TNBC experience the peak risk of recurrence within 3 years of diagnosis, and the mortality rates appear to be increased for 5 years after diagnosis. TNBC represents 10%–20% of invasive breast cancers and has been associated with African-American race, deprivation status, younger age at diagnosis, more advanced disease stage, higher grade, high mitotic indices, family history of breast cancer and <i>BRCA1</i> mutations. TNBC is regularly reported to be three times more common in women of African descent and in pre-menopausal women, and carries a poorer prognosis than other forms of breast cancer. Although prospects for prevention of non-hormone-dependent breast cancer are currently poor, it is still important to understand the aetiology of such tumours. There remains a great deal of work to be done to arrive at a comprehensive picture of the aetiology of breast cancer. Key recommendations are that there is a clear and urgent need to have more epidemiological studies of the breast cancer sub-types to integrate aetiological and lifestyle factors for prevention of incidence and death, and to have more population-based information of the clinical and biological relevance from cancer registries.
Clinical efficacy of leflunomide in primary Sjögren's syndrome is associated with regulation of T-cell activity and upregulation of IL-7 receptor α expression
Authors: Angela Bikker, Jan-Maarten van Woerkom, Aike A Kruize, Kim M G van der Wurff-Jacobs, Johannes W J Bijlsma, Floris P J G Lafeber, Joel A G van Roon
Journal: Annals of the Rheumatic Diseases (2012)

<h3>Objectives</h3> To investigate whether the immunomodulatory capacities of leflunomide are associated with clinical efficacy in the treatment of primary Sjögren9s syndrome (SS) in a phase II pilot study. <h3>Methods</h3> Peripheral blood mononuclear cells from 13 primary SS patients were obtained at baseline and after 24 weeks of leflunomide treatment. Ex-vivo production of interleukin (IL) 1β and tumour necrosis factor α (TNFα) and of interferon (IFN), IL-4, as well as TNFα ELISA measured production on T-cell and monocyte stimulation. In addition, the authors investigated the ability of leflunomide to influence systemic levels of inflammatory cytokines, as well as T-cell activation markers and the expression of IL-7 receptor α by flow cytometry. Correlations between changes in cytokine levels and changes in clinical response parameters were studied. <h3>Results</h3> Ex-vivo production of IL-1β and TNFα was decreased at 24 weeks in the whole patient group, whereas IFN and IL-4 production were not significantly changed. However, a significant decrease in T-cell-stimulated IFN and TNFα production was observed in clinical responders, but not in non-responders. Moreover, significant correlations were found between increased sialometry values and decreased IFN and TNFα production. In addition, leflunomide reduced levels of inflammatory serum cytokines and CD40L expression, whereas it upregulated IL-7Rα expression on CD4 T cells with persistent serum IL-7 concentrations. <h3>Conclusions</h3> Leflunomide treatment suppressed cytokine release from circulating immune cells. Inhibition of T-helper 1 cell cytokine production was related to clinical efficacy. This suggests that selective T-cell targeting might be a relevant therapeutic strategy in primary SS, possibly enhancing clinical efficacy and safety.
Randomized Clinical Trial of the Effectiveness of a Self-Care Intervention to Improve Cancer Pain Management
Authors: Christine Miaskowski, Marylin Dodd, Claudia West, Karen Schumacher, Steven M. Paul, Debu Tripathy, Peter Koo
Journal: Journal of Clinical Oncology (2004)

This randomized clinical trial tested the effectiveness of the PRO-SELF Pain Control Program compared with standard care in decreasing pain intensity scores, increasing appropriate analgesic prescriptions, and increasing analgesic intake in oncology outpatients with pain from bone metastasis.Patients were randomly assigned to the PRO-SELF intervention (n = 93) or standard care (n = 81). Patients in the standard care arm were seen by a research nurse three times and were called three times by phone between the home visits. PRO-SELF group patients were seen by specially trained intervention nurses and received a psychoeducational intervention, were taught how to use a pillbox, and were given written instructions on how to communicate with their physician about unrelieved pain and the need for changes in their analgesic prescriptions. Patients were coached during two follow-up home visits and three phone calls on how to improve their cancer pain management.Pain intensity scores decreased significantly from baseline (all P <.0001) in the PRO-SELF group (ie, least pain, 28.4%; average pain, 32.5%; and worst pain, 27.0%) compared with the standard care group (ie, least increased by 14.6%, average increased by 1.9%, and worst decreased by 1.2%). The percentage of patients in the PRO-SELF group with the most appropriate type of analgesic prescription increased significantly from 28.3% to 37.0% (P =.008) compared with a change from 29.6% to 32.5% in the standard care group.The use of a psychoeducational intervention that incorporates nurse coaching within the framework of self-care can improve the management of cancer pain.
Rat angiotensin II (type 1A) receptor mRNA regulation and subtype expression in myocardial growth and hypertrophy.
Authors: J Suzuki, H Matsubara, M Urakami, M Inada
Journal: Circulation Research (1993)

Two subtypes of angiotensin II (Ang II) receptors (AT1 and AT2) are distinguished by using the respective specific antagonists. In the present study, we report the regulation of cardiac AT1 type A (AT1A) receptor mRNA levels and the expression pattern of AT1 and AT2 receptors in the growth of the heart and the development and regression of cardiac hypertrophy. The ventricular AT1A mRNA level and the density of Ang II receptors at the neonatal period were significantly increased (3.5-fold and 2.5-fold, respectively) and then downregulated with maturation. The cardiac hypertrophy established in spontaneously hypertensive rats or two-kidney one-clip renovascular hypertensive rats resulted in substantial increases in ventricular AT1A mRNA levels (threefold) and Ang II receptor densities (twofold) as compared with those in respective control rats, whereas the receptor affinity was similar. The proportion of AT1 and AT2 subtypes in the specific Ang II binding in ventricular membranes prepared from normal adult rats was nearly equal. This proportion did not change significantly in the development of myocardial hypertrophy. The regression of cardiac hypertrophy by the normalization of elevated blood pressure completely reversed the increased levels of AT1A mRNA and the receptor density to the control level. Thus, AT1 and AT2 receptors are present in rat ventricular myocardium, and their expression is developmentally regulated and upregulated in response to hypertrophic change. Ang II action exerted through the increased number of Ang II receptors may contribute to the growth of the heart and thus to the maintenance of established hypertrophy as one of the hormones involved in hypertrophy development.
Effects of Environmental Enrichment at Ages 3–5 Years on Schizotypal Personality and Antisocial Behavior at Ages 17 and 23 Years
Authors: Adrian Raine, Kjetil Mellingen, Jianghong Liu, Peter Venables, Sarnoff A. Mednick
Journal: American Journal of Psychiatry (2003)

Methods to prevent two major mental disorders, schizophrenia and conduct disorder, have been elusive. This study assessed the effects of an early nutritional, educational, and physical exercise enrichment program on adult outcome for schizotypal personality, conduct disorder, and criminal behavior.Eighty-three children were assigned to an experimental enrichment program from ages 3 to 5 years and matched on temperament, nutritional, cognitive, autonomic, and demographic variables with 355 children who experienced usual community conditions (control group). Both self-report and objective measures of schizotypal personality and antisocial behavior were obtained when the subjects were ages 17 and 23 years.Subjects who participated in the enrichment program at ages 3-5 years had lower scores for schizotypal personality and antisocial behavior at age 17 years and for criminal behavior at age 23 years, compared with the control subjects. The beneficial effects of the intervention were greater for children who showed signs of malnutrition at age 3 years, particularly with respect to outcomes for schizotypy at ages 17 and 23 and for antisocial behavior at age 17.The results are consistent with an increasing body of knowledge that implicates an enriched, stimulating environment in beneficial psychological and behavioral outcomes. These findings have potential implications for the prevention of schizophrenia and criminal behavior.
Cardiovascular Events and Their Reduction With Pravastatin in Diabetic and Glucose-Intolerant Myocardial Infarction Survivors With Average Cholesterol Levels
Authors: Ronald B. Goldberg, Margot J. Mellies, Frank M. Sacks, Lemuel A. Moyé, Barbara V. Howard, William James Howard, Barry R. Davis, Thomas G. Cole, Marc A. Pfeffer, Eugene Braunwald
Journal: Circulation (1998)

Although diabetes is a major risk factor for coronary heart disease (CHD), little information is available on the effects of lipid lowering in diabetic patients. We determined whether lipid-lowering treatment with pravastatin prevents recurrent cardiovascular events in diabetic patients with CHD and average cholesterol levels.The Cholesterol And Recurrent Events (CARE) trial, a 5-year trial that compared the effect of pravastatin and placebo, included 586 patients (14.1%) with clinical diagnoses of diabetes. The participants with diabetes were older, more obese, and more hypertensive. The mean baseline lipid concentrations in the group with diabetes--136 mg/dL LDL cholesterol, 38 mg/dL HDL cholesterol, and 164 mg/dL triglycerides--were similar to those in the nondiabetic group. LDL cholesterol reduction by pravastatin was similar (27% and 28%) in the diabetic and nondiabetic groups, respectively. In the placebo group, the diabetic patients suffered more recurrent coronary events (CHD death, nonfatal myocardial infarction [MI], CABG, and PTCA) than did the nondiabetic patients (37% versus 25%). Pravastatin treatment reduced the absolute risk of coronary events for the diabetic and nondiabetic patients by 8.1% and 5.2% and the relative risk by 25% (P=0.05) and 23% (P<0.001), respectively. Pravastatin reduced the relative risk for revascularization procedures by 32% (P=0.04) in the diabetic patients. In the 3553 patients who were not diagnosed as diabetic, 342 had impaired fasting glucose at entry defined by the American Diabetes Association as 110 to 125 mg/dL. These nondiabetic patients with impaired fasting glucose had a higher rate of recurrent coronary events than those with normal fasting glucose (eg, 13% versus 10% for nonfatal MI). Recurrence rates tended to be lower in the pravastatin compared with placebo group (eg, -50%, P=0.05 for nonfatal MI).Diabetic patients and nondiabetic patients with impaired fasting glucose are at high risk of recurrent coronary events that can be substantially reduced by pravastatin treatment.
EFFECT OF SILICATE ON GRAM STAINING AND VIABILITY OF PNEUMOCOCCI AND OTHER BACTERIA
Authors: Colin M. MacLeod, Amy S. Roe
Journal: The Journal of Experimental Medicine (1956)

Application of silicate solutions to living or heat-killed pneumococci and to certain "viridans" streptococci causes their conversion from a Gram-positive to a Gram-negative state. The original staining properties can be restored by suspending the silicate-treated bacteria in alkaline solutions of various salts but not by simple washing in water. Living pneumococci and the strains of streptococci whose staining properties are similarly affected are killed when suspended in silicate solutions. In other Gram-positive species silicate causes conversion to Gram negativity but restoration to positivity occurs upon washing in water. In a third group of Gram-positive organisms silicate has no effect on the Gram reaction. The viability of organisms in these two groups is unaffected by silicate under the conditions employed. No effect on staining or viability of Gram-negative bacteria has been observed. The effects of silicate on staining and viability are inhibited by nutrient broth or whole serum but not by purified serum albumin. Lecithin, choline, and other substituted ammonium compounds also inhibit the effects of silicate on pneumococci.
The role of inflammatory biomarkers and health related quality of life questionnaires in distinction of exacerbation and stable chronic obstructive pulmonary diseases
Authors: Balam Er Dedekarginoglu, Elif Kupeli, Nilufer Bayraktar, Ersin Ogus, Gaye Ulubay
Journal: European Respiratory Journal (2014)

COPD is a preventable and treatable disease which is characterized by recurrent symptoms and exacerbations. Exacerbation diagnosis is established by according to patients' history and subjective symptoms. Although there is not any objective and definite parameters for diagnosis, emerging physical examination findings and inflammatory biomarkers can mostly be a guide in clinical practice.

In our study, we aimed to demonstrate the benefit of COPD Assessment Test (CAT) scores to diagnose exacerbation of COPD.

With this purpose, all COPD patients(n=53, M/F=40/13, mean±SD age= 68,6±1,1years) who was admitted to our hospital at the time of exacerbation were included in the study. The CAT score and inflammatory biomarkers of the patients were compared in both exacerbation period(EP) and stable period(SP) to evaluate whether CAT score of COPD patients could diagnose EP or not. We also examined the correlation between CAT score and, IL-6), CRP and SF-36 score of the patients.

The CAT score of the patients in SP was lower than in EP (mean ±CAT exacerbation=23,2±1,7 and mean±CATstable=15,0±1,0)(p<0,01). Likewise there was an improvement in SF-36 physical health scores in SP when compared with EP(p<0,05). The CAT score was correlated with IL-6(p=0,01), CRP(p= 0,01) and leucocytes(p=0,03) in the EP. No correlation has been found between the CAT scores in SP and the number of hospital admissions in the last one year due to exacerbations(p=0,02).

We suggested that, CAT could be a useful questionnaire to diagnose exacerbation of COPD regarding to its correlation with inflammatory biomarkers like CRP and IL-6.
Future of Royal Masonic Hospital
Authors: E J. Davies
Journal: BMJ (1993)

questionnaire.Overall we found that awareness of complementary medicine was high.All respondents recognised at least one kind of complementary treatment on being prompted, and 21 could name at least one spontaneously.Most (80%) had obtained their information from the media or friends and relatives rather than from health workers.Fourteen respondents had used complementary medicine at some time, four within the past year.Use was slightly more common among those of higher social class (p0-061).Only three people had used it together with orthodox medicine; the others had used it as the only treatment for their particular problem.All 14 users were satisfied with the results of complementary treatment, and 10 agreed that they would recommend it to others.Osteopathy, herbalism, homoeopathy, massage, and special diets were the commonest treatments used.Most (10) respondents had obtained their alternative treatments in Settle, where there were various sources, including an osteopath, two shops selling homoeopathic treatments, and a herbalist offering consultations in the weekly market.This study suggests that complementary treatments are readily available and that elderly patients have a high awareness of them and regard them positively.
Leptospira Outer Membrane Protein Activates NF-κB and Downstream Genes Expressed in Medullary Thick Ascending Limb Cells
Authors: CHIH-WEI YANG, MAI-SZU WU, MING-JENG PAN, JENN-JYE HONG, CHUN-CHEN YU, ALAIN VANDEWALLE, CHIU-CHING HUANG
Journal: Journal of the American Society of Nephrology (2000)

Abstract. Tubulointerstitial nephritis is the main manifestation of acute renal damage caused by leptospirosis, but the mechanism remains unexplored. Patients infected with Leptospira shermani in Taiwan disclosed tubular dysfunction particularly in the medullary thick ascending limb of loop of Henle (mTAL), and the related renal damage seems to be underestimated. To elucidate the mechanism of tubular damage, outer membrane protein extract from Leptospira was administered to a model of cultured mTAL cells derived from normal mice. The addition of outer membrane protein extract from L. shermani to cultured mTAL cells induced a significant nuclear DNA binding of the NF-κ B transcription factor by electrophoresis mobility shift assay. Forty-eight h after adding the outer membrane protein extract (0.2 μg/ml) to the cultured cells, the expression of inducible nitric oxide mRNA increased by 4.2-fold, monocyte chemoattractant protein-1 by 3-fold, and tumor necrosis factor-α by 2.4-fold when compared with untreated cells examined by reverse transcription competitive-PCR. Supernatant nitrite, monocyte chemoattractant protein-1, and tumor necrosis factor-α protein levels also increased by 1.8-, 7.1-, and 5-fold, respectively. An antiserum raised against L. shermani largely prevented these effects. Outer membrane protein extract from L. bratislava induced fewer effects than L. shermani , and the avirulent nonpathogenic L. biflexa serovar patoc did not induce significant effects in the mTAL cells. In conclusion, L. shermani infection may cause mTAL cell damage and inflammation through the NF-κ B—associated pathway. Findings of this study may be important in understanding the pathogenesis of tubulointerstitial nephritis caused by these organisms.