tbuckley/cabot-search huggingface dataset:
NKX3.1 Suppresses <i>TMPRSS2–ERG</i> Gene Rearrangement and Mediates Repair of Androgen Receptor–Induced DNA Damage
Authors: Cai Bowen, Tian Zheng, Edward P. Gelmann
Journal: Cancer Research (2015)

Abstract TMPRSS2 gene rearrangements occur at DNA breaks formed during androgen receptor–mediated transcription and activate expression of ETS transcription factors at the early stages of more than half of prostate cancers. NKX3.1, a prostate tumor suppressor that accelerates the DNA repair response, binds to androgen receptor at the ERG gene breakpoint and inhibits both the juxtaposition of the TMPRSS2 and ERG gene loci and also their recombination. NKX3.1 acts by accelerating DNA repair after androgen-induced transcriptional activation. NKX3.1 influences the recruitment of proteins that promote homology-directed DNA repair. Loss of NKX3.1 favors recruitment to the ERG gene breakpoint of proteins that promote error-prone nonhomologous end-joining. Analysis of prostate cancer tissues showed that the presence of a TMPRSS2–ERG rearrangement was highly correlated with lower levels of NKX3.1 expression consistent with the role of NKX3.1 as a suppressor of the pathogenic gene rearrangement. Cancer Res; 75(13); 2686–98. ©2015 AACR.
“Borrelia-associated early-onset morphea”: A particular type of scleroderma in childhood and adolescence with high titer antinuclear antibodies?
Authors: Joerg C. Prinz, Zsuzsanna Kutasi, Peter Weisenseel, László Pótó, Zita Battyáni, Thomas Ruzicka
Journal: Journal of the American Academy of Dermatology (2008)
Combined kidney and pancreatic transplantation
Authors: A Kumar, C G Newstead, J P A Lodge, A M Davison
Journal: BMJ (1999)

Diabetes mellitus is the single most common cause of end stage renal failure in Western societies. Despite rigorous glycaemic control, dietary changes, exercise, and use of disease modifying drugs, some patients with diabetes, mostly but not exclusively those with type 1 disease, will develop renal failure requiring dialysis.1 In the first five years after transplantation, kidney graft survival is similar in diabetic and non-diabetic populations,2 but overall mortality in the diabetic group is three times that in non-diabetic transplant recipients.3Accelerated coronary atherosclerosis, sudden death related to autonomic neuropathy, and infection account for much of this excess mortality. Strict control of blood glucose with intensive insulin therapy reduces, but does not eliminate, these risks.1 In the United States simultaneous kidney and pancreas transplantation is now regarded by many clinicians as the treatment of choice for uraemic diabetic …
Possible Positive Selection for an Arsenic-Protective Haplotype in Humans
Authors: Carina M. Schlebusch, Cecil M. Lewis, Marie Vahter, Karin Engström, Raúl Y. Tito, Alexandra J. Obregón-Tito, Doris Huerta, Susan I. Polo, Ángel C. Medina, Tom D. Brutsaert, Gabriela Concha, Mattias Jakobsson, Karin Broberg
Journal: Environmental Health Perspectives (2012)

Arsenic in drinking water causes severe health effects. Indigenous people in the South American Andes have likely lived with arsenic-contaminated drinking water for thousands of years. Inhabitants of San Antonio de los Cobres (SAC) in the Argentinean highlands generally carry an AS3MT (the major arsenic-metabolizing gene) haplotype associated with reduced health risks due to rapid arsenic excretion and lower urinary fraction of the monomethylated metabolite.We hypothesized an adaptation to high-arsenic living conditions via a possible positive selection for protective AS3MT variants and compared AS3MT haplotype frequencies among different indigenous groups.Indigenous groups we evaluated were a) inhabitants of SAC and villages near Salta in northern Argentina (n = 346), b) three Native American populations from the Human Genome Diversity Project (HGDP; n = 25), and c) five Peruvian populations (n = 97). The last two groups have presumably lower historical exposure to arsenic.We found a significantly higher frequency of the protective AS3MT haplotype in the SAC population (68.7%) compared with the HGDP (14.3%, p < 0.001, Fisher exact test) and Peruvian (50.5%, p < 0.001) populations. Genome-wide microsatellite (n = 671) analysis showed no detectable level of population structure between SAC and Peruvian populations (measure of population differentiation FST = 0.006) and low levels of structure between SAC and HGDP populations (FST < 0.055 for all pairs of populations compared).Because population stratification seems unlikely to explain the differences in AS3MT haplotype frequencies, our data raise the possibility that, during a few thousand years, natural selection for tolerance to the environmental stressor arsenic may have increased the frequency of protective variants of AS3MT. Further studies are needed to investigate this hypothesis.
Coping with bioterrorism
Authors: P. Rosen
Journal: BMJ (2000)

The terror attacks on the World Trade Center in Manhattan in 1993 and the Federal Building in Oklahoma City in 1995, together with the Sarin attack on the Tokyo subway in 1995, have forced upon America an unwanted awareness of its vulnerability to terror attack. So far there have been no biological attacks within the United States, but many feel that this may only be a matter of time. Recently the Institute of Medicine and the National Academy of Sciences have made recommendations for research that would help in managing chemical and biological terror attacks against the civilian community.1

There are specific problems that are unique to biological attacks. Firstly, whatever the agent, and however it is delivered, there will be time lags between exposure and onset of the first symptoms and the development of the full blown disease. Thus the disease will be dispersed before we become aware that an attack has occurred (assuming no public announcement by the terrorists). Since the population exposed in a large community will approach the health system in many different ways there may be no clumping of cases to trigger awareness of an attack.

Secondly, the early manifestations caused by virtually any of the biological agents will look identical clinically. It is currently impossible to distinguish viral from bacterial disease until a specific organ pathophysiology declares itself, and this will probably be true also for a biological weapon. Moreover, …
Phylogenetic groups and virulence factors of Escherichia coli strains causing pyelonephritis in children with and without urinary tract abnormalities
Authors: V. Houdouin, S. Bonacorsi, F. Mahjoub-Messai, P. Mariani-Kurkdjian, P. Bidet, G. Sebag, C. Loirat, A. Bourrillon, E. Bingen
Journal: Clinical Microbiology and Infection (2007)
Malignant Pleural Mesothelioma
Authors: David S. Ettinger, Wallace Akerley, Hossein Borghaei, Andrew Chang, Richard T. Cheney, Lucian R. Chirieac, Thomas A. D'Amico, Todd L. Demmy, Apar Kishor P. Ganti, Ramaswamy Govindan, Frederic W. Grannis, Leora Horn, Thierry M. Jahan, Mohammad Jahanzeb, Anne Kessinger, Ritsuko Komaki, Feng-Ming (Spring) Kong, Mark G. Kris, Lee M. Krug, Inga T. Lennes, Billy W. Loo, Renato Martins, Janis O'Malley, Raymond U. Osarogiagbon, Gregory A. Otterson, Jyoti D. Patel, Mary Pinder Schenck, Katherine M. Pisters, Karen Reckamp, Gregory J. Riely, Eric Rohren, Scott J. Swanson, Douglas E. Wood, Stephen C. Yang
Journal: Journal of the National Comprehensive Cancer Network (2012)

Mesothelioma is a rare cancer that is estimated to occur in approximately 2500 people in the United States every year. 1,2These NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines) focus on malignant pleural mesothelioma (MPM), which is the most common type; mesothelioma can also occur in other sites (e.g., peritoneum, pericardium, tunica vaginalis testis).The disease is difficult to treat;
Abstract 592: Enhance Fibroblast Growth Factor Receptor Signaling in VE-Cadherin-RTEF-1 Transgenic Mice
Authors: Qinhui Song, Isabelle Lubenec, Cuili Zhang, Dongmei Li, Jian Li
Journal: Circulation (2007)

Background: We have recently demonstrated that Related Transcription Enhancer Factor-1 (RTEF-1) is a transcription factor in endothelial cells. We also established that RTEF-1 regulated VEGF promot...
Late-breaking abstract: Repeated analysis of alpha-1-antitrypsin concentrations in sputum, lavage and serum of smokers with and without COPD
Authors: Olaf Holz, Stefan Roepcke, Gereon Lauer, Norbert Krug, Peter Ernst, Claudia Diefenbach, Gezim Lahu, Jens Hohlfeld
Journal: European Respiratory Journal (2011)

Introduction: Alpha-1-antitrypsin (A1AT)-deficiency is a hereditary disease that can lead to the development of emphysema. Serum levels of A1AT are used for diagnosis and monitoring during substitution therapy.

Aim: We have previously shown that A1AT levels differ between smokers with and without COPD (Roepcke et al. ERS2010). Here we assessed the repeatability of A1AT levels in serum, induced sputum (IS) and bronchoalveolar lavage (BAL) over a period of 6 weeks and compared the concentrations between compartments.

Methods: 24 COPD patients (GOLD II) and 23 age and gender matched healthy controls were included into the study. All were current smokers (≥ ten pack-years). Blood, BAL, and IS were collected on two occasions. A1AT was analyzed by ELISA, CRP by Luminex.

Results: The median (IQR) A1AT concentrations was 1.69 (0.53) g/L in serum, 505 (596) μg/L in BAL and 568 (475) μg/L in IS. The reproducibility between visits within each matrix was good (serum: r=0.55, p<0.001; BAL: r=0.72, p<0.001; IS: r=0.72, p<0.001). While there was a weak relationship between mean BAL and IS A1AT concentrations (r=0.36, p=0.03), no relationship was observed between serum and lung concentrations. BAL and IS A1AT levels did not correlate with neutrophils in the respective compartment or serum CRP, and only a weak correlation between serum A1AT, blood neutrophils (r=0.31, p=0.04) and CRP (r=0.32, p=0.04) was observed.

Conclusion: A1AT appears to be stable within compartments in healthy smokers and smokers with moderate COPD. The lack of relationship between lung and serum A1AT should be considered when interpreting serum A1AT for diagnostic and monitoring purposes.
Reducing hospital admission through computer supported education for asthma patients
Authors: L M Osman, M I Abdalla, J A G Beattie, S J Ross, I T Russell, J A Friend, J S Legge, J G Douglas
Journal: BMJ (1994)

To evaluate a personalised computer supported education programme for asthma patients.Pragmatic randomised trial comparing outcomes over 12 months between patients taking part in an enhanced education programme (four personalised booklets, sent by post) and patients receiving conventional oral education at outpatient or surgery visits.Hospital outpatient clinics and general practices in north east Scotland.801 adults attending hospital outpatient clinics, with a diagnosis of asthma confirmed by a chest physician and pulmonary function reversibility of at least 20%.Numbers of hospital admissions, consultations with general practitioner for asthma, steroid courses used, bronchodilators and inhaled steroids prescribed, days of restricted activity, and disturbed nights.Patients with asthma judged too severe for randomisation between clinic care and integrated care and thus retained in clinic care had 54% fewer hospital admissions after receiving enhanced education than did the control group (95% confidence interval 30% to 97%; P < 0.05) over the study year. Patients had not all spent a full year as "educated" patients within the study year: when "educated days" were controlled for, annual admission rates for the entire enhanced education group were 49% (31% to 78%) of those in the control group. Among patients with sleep variation, sleep disturbance in the education group in the week before a regular review was 80% (65% to 97%) of that in the control group. There was no significant difference in days of restricted activity, prescription of bronchodilators or inhaled steroids, use of oral steroids, or number of general practitioner consultations for asthma, and no significant interaction between ownership of a peak flow meter and education.An asthma education programme based on computerised booklets can reduce hospital admissions and improve morbidity among hospital outpatients.
Community Psychiatry at UCLA : A Decade of Training
Authors: MARVIN KARNO, JOHN G. KENNEDY, SANDRA LIPSCHULTZ
Journal: American Journal of Psychiatry (1974)

The community psychiatry training program at the University of California, Los Angeles (UCLA), a two-year postresidency program leading to a Master of Social Psychiatry degree, has been in existence for more than ten years. The authors describe the development of the curriculum and other aspects of the program and give results of a questionnaire returned by 41 of the 44 graduates of the program describing its effect on their careers.
Assessment of the physiologic significance of coronary disease with dipyridamole real-time myocardial contrast echocardiography
Authors: Marcel Peltier, David Vancraeynest, Agnès Pasquet, Taniyel Ay, Véronique Roelants, Anne-Marie D'hondt, Jacques A. Melin, Jean-Louis J. Vanoverschelde
Journal: Journal of the American College of Cardiology (2004)
Sexual identity of 37 children raised by homosexual or transsexual parents
Authors: Richard Green
Journal: American Journal of Psychiatry (1978)

The author reports on 37 children who are being raised by female homosexuals or by parents who have changed sex (transsexuals): 21 by female homosexuals, 7 by male-to-female transsexuals, and 9 by female-to-male transsexuals. The children range in age from 3 to 20 years (mean = 9.3) and have lived in the sexually atypical households for 1-16 years (mean = 4.9). Thirty-six of the children report or recall childhood toy, game, clothing, and peer group preferences that are typical for their sex. The 13 older children who report erotic fantasies or overt sexual behaviors are all heterosexually oriented.
Therapy of Gastrointestinal Fistulas with Fibrin Sealant
Authors: M. Jung, B. C. Manegold
Journal: Endoscopy (1995)

Gastrointestinal and respiratory fistulas are commonly associated with a prolonged and complicated clinical course. The technique of endoscopic fistula treatment using fibrin tissue adhesives was developed during the past decade. Fibrin sealing can be achieved by endoscopic application of a two-component system (Tissucol) which promotes the normal process of wound healing. The substance was first used in babies in closing isolated hair fistulas and esophageal recurrent fistulas after surgical correction of esophageal atresia. From 1974–1990, 14 babies with recurrent fistulas were treated with Tissucol (n = 12) and formerly with Histoacryl (n = 2). Endoscopic closure was successful in 11 out of the 14 babies. In two further children endoscopic therapy was successful in gluing broad submucosal lesions in the colonic wall following bougienage and sealing a small perforation in the esophagus following dilatation of a benign stenosis. Since 1984 indication for sealing gastrointestinal and tracheobronchial fistulas in adults has been extended. Esophageal fistulas seem to be a very suitable field for fibrin sealant application. Critically ill patients with anastomotic leakages in the esophagus, perforation due to radiotherapy, trauma, endoscopic procedure, or inflammatory disease were treated as well as patients with tumor fistulas. Endoscopic closures of fistulas were successful in 19 out of 24 patients in one to four sessions. Fibrin sealing failed in nearly all cases of tumor fistulas and in wide infected leakiness. Ineffective results can be caused by incorrect preparation and application of the substance and by early stressing the fibrin clot within the first 24 h. Nevertheless, the endoscopic procedure is especially of interest in critically ill patients and may be today an attractive alternative to major surgical procedures.
Celastrol Protects against Obesity and Metabolic Dysfunction through Activation of a HSF1-PGC1α Transcriptional Axis
Authors: Xinran Ma, Lingyan Xu, Anna Teresa Alberobello, Oksana Gavrilova, Alessia Bagattin, Monica Skarulis, Jie Liu, Toren Finkel, Elisabetta Mueller
Journal: Cell Metabolism (2015)
Female Hormonal Factors and the Risk of Endometrial Cancer in Lynch Syndrome
Authors: Seyedeh Ghazaleh Dashti, Rowena Chau, Driss Ait Ouakrim, Daniel D. Buchanan, Mark Clendenning, Joanne P. Young, Ingrid M. Winship, Julie Arnold, Dennis J. Ahnen, Robert W. Haile, Graham Casey, Steven Gallinger, Stephen N. Thibodeau, Noralane M. Lindor, Loïc Le Marchand, Polly A. Newcomb, John D. Potter, John A. Baron, John L. Hopper, Mark A. Jenkins, Aung Ko Win
Journal: JAMA (2015)

IMPORTANCE Apart from hysterectomy, there is no consensus recommendation for reducing endometrial cancer risk for women with a mismatch repair gene mutation (Lynch syndrome).OBJECTIVE To investigate the association between hormonal factors and endometrial cancer risk in Lynch syndrome. DESIGN, SETTING, AND PARTICIPANTSA retrospective cohort study included 1128 women with a mismatch repair gene mutation identified from the Colon Cancer Family Registry.Data were analyzed with a weighted cohort approach.Participants were recruited between 1997 and 2012 from centers across the United States, Australia, Canada, and New Zealand.EXPOSURES Age at menarche, first and last live birth, and menopause; number of live births; hormonal contraceptive use; and postmenopausal hormone use. MAIN OUTCOMES AND MEASURES Self-reported diagnosis of endometrial cancer.RESULTS Endometrial cancer was diagnosed in 133 women (incidence rate per 100 person-years, CONCLUSIONS AND RELEVANCE For women with a mismatch repair gene mutation, some endogenous and exogenous hormonal factors were associated with a lower risk of endometrial cancer.These directions and strengths of associations were similar to those for the general population.If replicated, these findings suggest that women with a mismatch repair gene mutation may be counseled like the general population in regard to hormonal influences on endometrial cancer risk.
Association of Electrocardiographic and Imaging Surrogates of Left Ventricular Hypertrophy With Incident Atrial Fibrillation
Authors: Jonathan Chrispin, Aditya Jain, Elsayed Z. Soliman, Eliseo Guallar, Alvaro Alonso, Susan R. Heckbert, David A. Bluemke, João A.C. Lima, Saman Nazarian
Journal: Journal of the American College of Cardiology (2014)
Primary Prevention Lipid-Lowering Drug Therapy
Authors: Donald O. Fedder, Carol E. Koro, Gilbert J. L’Italien
Journal: Circulation (2002)

issue of Circulation, 2 but we wish to respond to several issues raised.The methodology used to project population size is standard for the Third National Health and Nutrition Examination Survey (NHANES III) and is described thoroughly in the publication by the National Center for Health Statistics, which we reference 3 in our article.We did not feel it necessary to reiterate that method.We assume that the phrase "significance of the data" is a reference to statistical significance testing which remains a controversial issue in some epidemiological analyses. 4Given the large sample size inherent to these types of studies, even small differences can be declared statistically significant with very low probability values.We therefore felt that a list of highly significant probability values would not add to the interpretation of results.With regard to under-reporting of coronary heart disease, as Gotto and Kuller admit, the estimates in the survey reflect the misdiagnosis of coronary heart disease in women and elderly in actual practice.Because these same criteria will be used to determine eligibility for treatment in the clinician's office, we maintain that the same level of misclassification will occur in the office as in the NHANES III survey.Thus, our estimates represent those who would be so classified (as primary) in actual practice.Admittedly, "other forms of cardiovascular disease (CVD)," such as peripheral artery disease and symptomatic carotid disease, would be detectable in clinical practice.These will not constitute a large percentage of the total misclassified.Lastly, our estimates for primary prevention treatment-eligible patients under Adult Treatment Panel II correspond closely to those reported by Hoerger et al. 5 That study reported 15.7 million patients aged Ն20 years as treatment eligible.Our study reported a similar number (15.1 million) for those aged 20 to 79 years.We disagree with the conclusion that "more women than men aged 20 to 29 years are eligible for primary prevention."In fact, the observed difference is actually very small (78 735) relative to the total eligible population in that age group (2.4 million).We agree that global risk assessment is preferable to the narrow application of the Adult Treatment Panel III algorithm.However, it is unclear how the clinician will combine the algorithm's quantitative output with the list of global risk factors (Table 2 of the editorial 1 ) to decide treatment.That subjective judgment could not be reliably incorporated into our analyses.The fact remains that Ͼ70% of the eligible patients can be selected for treatment solely on the basis of having a low-density lipoprotein cholesterol level Ն160 mg/dL.
In praise of small studies
Authors: B.L. Diffey
Journal: British Journal of Dermatology (2011)

Conflicts of interest None declared. It is a profound and necessary truth that the deep things in science are not found because they are useful; they are found because it was possible to find them.– Robert Oppenheimer Melanoma and vitamin D synthesis are the two impacts of cutaneous sun exposure that provoke the greatest concern, debate and controversy and these are brought together in a study reported in this issue by researchers from Copenhagen.1 In a small study they showed that following a diagnosis of melanoma, patients changed their habits to receive lower sun exposure than before diagnosis, using changes in serum 25‐hydroxyvitamin D [25(OH)D] and skin pigmentation before and after diagnosis as proxy measures of ultraviolet (UV) exposure. Furthermore, they showed that winter levels of 25(OH)D immediately following diagnosis were higher than in a control group or in patients diagnosed up to 6 years previously and inferred from this that in the summer leading up to diagnosis, sun exposure was especially high.
Targeting CD123 In Leukemic Stem Cells Using Dual Affinity Re-Targeting Molecules (DARTs®)
Authors: Muneera H. AL Hussaini, Julie Ritchey, Michael P. Rettig, Linda Eissenberg, Geoffrey L. Uy, Gurunadh Chichili, Paul A Moore, Syd Johnson, Lynne Collins, Ezio Bonvini, John F. DiPersio
Journal: Blood (2013)
Rapid cycling affective disorder: contributing factors and treatment responses in 51 patients
Authors: T A Wehr, D A Sack, N E Rosenthal, R W Cowdry
Journal: American Journal of Psychiatry (1988)

For 51 patients with rapid cycling affective disorder, clinical and family history data indicated that the illness was phenotypically and genetically related to more typical forms of affective disorder, was characterized by a bipolar course (100%), and was more common in women (92%). Manic-depressive cycles were separate from menstrual cycles. At the time of onset of rapid cycling, 73% of the patients were taking antidepressant drugs; the continuation of rapid cycling was associated with antidepressant drug therapy in 51% of the patients. Although most patients had been referred to a research ward because they were considered to be refractory to treatment, 37% attained essentially complete remissions, usually during treatment with lithium and/or monoamine oxidase inhibitors.
Abstract 5795: 2D vs 3D Transesophageal Echo in the Assessment of the Aortic Annulus for Transcatheter Aortic Valve Implantation
Authors: Amit Bhan, Stamatis Kapetanakis, Karen Wilson, Peter Pearson, Olaf Wendler, Ahmed El-Gamel, Philip MacCarthy, Martyn R Thomas, Mark J Monaghan
Journal: Circulation (2008)

Transcatheter aortic valve implantation (TAVI) is a relatively new procedure, currently for those in whom conventional surgery is too high risk. Preliminary data has been encouraging and a number o...