tbuckley/cabot-search huggingface dataset:
Long-Term Outcomes Among Adult Survivors of Childhood Central Nervous System Malignancies in the Childhood Cancer Survivor Study
Authors: Gregory T. Armstrong, Qi Liu, Yutaka Yasui, Sujuan Huang, Kirsten K. Ness, Wendy Leisenring, Melissa M. Hudson, Sarah S. Donaldson, Allison A. King, Marilyn Stovall, Kevin R. Krull, Leslie L. Robison, Roger J. Packer
Journal: JNCI Journal of the National Cancer Institute (2009)

Adult survivors of childhood central nervous system (CNS) malignancies are at high risk for long-term morbidity and late mortality. However, patterns of late mortality, the long-term risks of subsequent neoplasms and debilitating medical conditions, and sociodemographic outcomes have not been comprehensively characterized for individual diagnostic and treatment groups. We collected information on treatment, mortality, chronic medical conditions, and neurocognitive functioning of adult 5-year survivors of CNS malignancies diagnosed between 1970 and 1986 within the Childhood Cancer Survivor Study. Using competing risk framework, we calculated cumulative mortality according to cause of death and cumulative incidence of subsequent neoplasms according to exposure and dose of cranial radiation therapy (RT). Neurocognitive impairment and socioeconomic outcomes were assessed with respect to dose of CNS radiotherapy to specific brain regions. Cumulative incidence of chronic medical conditions was compared between survivors and siblings using Cox regression models. All tests of statistical significance were two-sided. Among all eligible 5-year survivors (n = 2821), cumulative late mortality at 30 years was 25.8% (95% confidence interval [CI] = 23.4% to 28.3%), due primarily to recurrence and/or progression of primary disease. Patients who received cranial RT of 50 Gy or more (n = 813) had a cumulative incidence of a subsequent neoplasm within the CNS of 7.1% (95% CI = 4.5% to 9.6%) at 25 years from diagnosis compared with 1.0% (95% CI = 0% to 2.3%) for patients who had no RT. Survivors had higher risk than siblings of developing new endocrine, neurological, or sensory complications 5 or more years after diagnosis. Neurocognitive impairment was high and proportional to radiation dose for specific tumor types. There was a dose-dependent association between RT to the frontal and/or temporal lobes and lower rates of employment, and marriage. Survivors of childhood CNS malignancies are at high risk for late mortality and for developing subsequent neoplasms and chronic medical conditions. Care providers should be informed of these risks so they can provide risk-directed care and develop screening guidelines.
High-density genotyping of immune loci in Koreans and Europeans identifies eight new rheumatoid arthritis risk loci
Authors: Kwangwoo Kim, So-Young Bang, Hye-Soon Lee, Soo-Kyung Cho, Chan-Bum Choi, Yoon-Kyoung Sung, Tae-Hwan Kim, Jae-Bum Jun, Dae Hyun Yoo, Young Mo Kang, Seong-Kyu Kim, Chang-Hee Suh, Seung-Cheol Shim, Shin-Seok Lee, Jisoo Lee, Won Tae Chung, Jung-Yoon Choe, Hyoung Doo Shin, Jong-Young Lee, Bok-Ghee Han, Swapan K Nath, Steve Eyre, John Bowes, Dimitrios A Pappas, Joel M Kremer, Miguel A Gonzalez-Gay, Luis Rodriguez-Rodriguez, Lisbeth Ärlestig, Yukinori Okada, Dorothée Diogo, Katherine P Liao, Elizabeth W Karlson, Soumya Raychaudhuri, Solbritt Rantapää-Dahlqvist, Javier Martin, Lars Klareskog, Leonid Padyukov, Peter K Gregersen, Jane Worthington, Jeffrey D Greenberg, Robert M Plenge, Sang-Cheol Bae
Journal: Annals of the Rheumatic Diseases (2014)

<h3>Objective</h3> A highly polygenic aetiology and high degree of allele-sharing between ancestries have been well elucidated in genetic studies of rheumatoid arthritis. Recently, the high-density genotyping array Immunochip for immune disease loci identified 14 new rheumatoid arthritis risk loci among individuals of European ancestry. Here, we aimed to identify new rheumatoid arthritis risk loci using Korean-specific Immunochip data. <h3>Methods</h3> We analysed Korean rheumatoid arthritis case–control samples using the Immunochip and genome-wide association studies (GWAS) array to search for new risk alleles of rheumatoid arthritis with anticitrullinated peptide antibodies. To increase power, we performed a meta-analysis of Korean data with previously published European Immunochip and GWAS data for a total sample size of 9299 Korean and 45 790 European case–control samples. <h3>Results</h3> We identified eight new rheumatoid arthritis susceptibility loci (<i>TNFSF4</i>, <i>LBH</i>, <i>EOMES</i>, <i>ETS1–FLI1</i>, <i>COG6</i>, <i>RAD51B</i>, <i>UBASH3A</i> and <i>SYNGR1</i>) that passed a genome-wide significance threshold (p&lt;5×10<sup>−8</sup>), with evidence for three independent risk alleles at 1q25/<i>TNFSF4</i>. The risk alleles from the seven new loci except for the <i>TNFSF4</i> locus (monomorphic in Koreans), together with risk alleles from previously established RA risk loci, exhibited a high correlation of effect sizes between ancestries. Further, we refined the number of single nucleotide polymorphisms (SNPs) that represent potentially causal variants through a trans-ethnic comparison of densely genotyped SNPs. <h3>Conclusions</h3> This study demonstrates the advantage of dense-mapping and trans-ancestral analysis for identification of potentially causal SNPs. In addition, our findings support the importance of T cells in the pathogenesis and the fact of frequent overlap of risk loci among diverse autoimmune diseases.
Robotic Versus Laparoscopic Partial Nephrectomy: A Systematic Review and Meta-Analysis
Authors: Omar M. Aboumarzouk, Robert J. Stein, Remi Eyraud, Georges-Pascal Haber, Piotr L. Chlosta, Bhaskar K. Somani, Jihad H. Kaouk
Journal: European Urology (2012)
Combination of p53 Cancer Vaccine with Chemotherapy in Patients with Extensive Stage Small Cell Lung Cancer
Authors: Scott J. Antonia, Noweeda Mirza, Ingo Fricke, Alberto Chiappori, Patricia Thompson, Nicholas Williams, Gerold Bepler, George Simon, William Janssen, Ji-Hyun Lee, Kerstin Menander, Sunil Chada, Dmitry I. Gabrilovich
Journal: Clinical Cancer Research (2006)

Abstract Purpose: The initial goal of this study was to test the immunologic and clinical effects of a new cancer vaccine consisting of dendritic cells (DC) transduced with the full-length wild-type p53 gene delivered via an adenoviral vector in patients with extensive stage small cell lung cancer. Experimental Design: Twenty-nine patients with extensive stage small cell lung cancer were vaccinated repeatedly at 2-week intervals. Most of the patients received three immunizations. p53-specific responses were evaluated, and phenotype and function of T cells, DCs, and immature myeloid cells were analyzed and correlated with antigen-specific immune responses. Objective clinical response to vaccination as well as subsequent chemotherapy was evaluated. Results: p53-specific T cell responses to vaccination were observed in 57.1% of patients. Immunologic responses to vaccination were positively associated with a moderate increase in the titer of antiadenovirus antibodies, and negatively with an accumulation of immature myeloid cells. One patient showed a clinical response to vaccination whereas most of the patients had disease progression. However, we observed a high rate of objective clinical responses to chemotherapy (61.9%) that immediately followed vaccination. Clinical response to subsequent chemotherapy was closely associated with induction of immunologic response to vaccination. Conclusions: This study provides clinical support for an emerging paradigm in cancer immunotherapy, wherein optimal use of vaccination might be more effective, not as a separate modality, but in direct combination with chemotherapy.
Sexual behaviour of heterosexual men and women receiving antiretroviral pre-exposure prophylaxis for HIV prevention: a longitudinal analysis
Authors: Kenneth K Mugwanya, Deborah Donnell, Connie Celum, Katherine K Thomas, Patrick Ndase, Nelly Mugo, Elly Katabira, Kenneth Ngure, Jared M Baeten
Journal: The Lancet Infectious Diseases (2013)
THE EFFECT OF CLOPENTHIXOL ON CHRONIC PSYCHIATRIC PATIENTS
Authors: T. A. BAN, K. FERGUSON, H. E. LEHMANN
Journal: American Journal of Psychiatry (1963)

In our clinical trial with 20 male chronic patients on a mental hospital ward, clopenthixol appeared to have observable antipsychotic properties with relatively little toxicity. The observation that this drug was therapeutically effective in certain chronic sohizaphrenic patients where previous treatments had failed is in accordance with the findings of other clinical investigators and suggests that clopenthixol may deserve a place among the clinically used antipsychotic compounds.
Genotype-Phenotype Comparison of German <i>MLH1</i> and <i>MSH2</i> Mutation Carriers Clinically Affected With Lynch Syndrome: A Report by the German HNPCC Consortium
Authors: Timm Goecke, Karsten Schulmann, Christoph Engel, Elke Holinski-Feder, Constanze Pagenstecher, Hans K. Schackert, Matthias Kloor, Erdmute Kunstmann, Holger Vogelsang, Gisela Keller, Wolfgang Dietmaier, Elisabeth Mangold, Nicolaus Friedrichs, Peter Propping, Stefan Krüger, Johannes Gebert, Wolff Schmiegel, Josef Rueschoff, Markus Loeffler, Gabriela Moeslein
Journal: Journal of Clinical Oncology (2006)

Lynch syndrome is linked to germline mutations in mismatch repair genes. We analyzed the genotype-phenotype correlations in the largest cohort so far reported.Following standard algorithms, we identified 281 of 574 unrelated families with deleterious germline mutations in MLH1 (n = 124) or MSH2 (n = 157). A total of 988 patients with 1,381 cancers were included in this analysis.We identified 181 and 259 individuals with proven or obligatory and 254 and 294 with assumed MLH1 and MSH2 mutations, respectively. Age at diagnosis was younger both in regard to first cancer (40 v 43 years; P < .009) and to first colorectal cancer (CRC; 41 v 44 years; P = .004) in MLH1 (n = 435) versus MSH2 (n = 553) mutation carriers. In both groups, rectal cancers were remarkably frequent, and the time span between first and second CRC was smaller if the first primary occurred left sided. Gastric cancer was the third most frequent malignancy occurring without a similarly affected relative in most cases. All prostate cancers occurred in MSH2 mutation carriers.The proportion of rectal cancers and shorter time span to metachronous cancers indicates the need for a defined treatment strategy for primary rectal cancers in hereditary nonpolyposis colorectal cancer patients. Male MLH1 mutation carriers require earlier colonoscopy beginning at age 20 years. We propose regular gastric surveillance starting at age 35 years, regardless of the familial occurrence of this cancer. The association of prostate cancer with MSH2 mutations should be taken into consideration both for clinical and genetic counseling practice.
Referral for lung transplantation: experience of a Birmingham Adult Cystic Fibrosis Centre between 1987 and 1994.
Authors: P J Ryan, D E Stableforth
Journal: Thorax (1996)

BACKGROUND: Whilst much is known of the outcome of lung transplantation for patients with cystic fibrosis, less is known about those patients who are either not referred for transplantation or who die before a donor is available. The referral practice and outcome of all the cystic fibrosis patients in one clinic was documented, whether or not they were assessed for lung transplantation. The results give a perspective on the impact of the current transplantation programmes on the adult cystic fibrosis population as a whole. METHODS: A retrospective study was made of patient deaths and referrals for lung transplantation between 1987 and 1994 from the Adult Cystic Fibrosis Clinic at Birmingham Heartlands Hospital. RESULTS: The Birmingham Heartlands Adult Cystic Fibrosis Clinic has managed 192 patients since its beginning and currently cares for 141 patients. Since 1987 there have been 16 deaths in patients with cystic fibrosis who were considered unsuitable for lung transplantation. Of 49 patients referred for lung transplantation, 47 were accepted on to a provisional or active waiting list. The mean (SE) age at referral was 23.9 (0.7) years and mean (SE) forced expiratory volume in one second (FEV1) was 0.87 (0.04) 1. Fourteen patients died whilst awaiting transplantation and 19 received donor lungs. There have been 10 deaths in the transplanted group. Survival following transplantation was 58% at one year and 52% at two years. CONCLUSION: Most of the deaths that occurred in the Cystic Fibrosis Clinic were in patients who either were not considered suitable for transplantation or were still awaiting transplantation. Whilst lung transplantation is the focus for many adults with cystic fibrosis, lack of donor organs has limited the impact of transplant programmes on the clinic.
Sleep on the cheap: the role of overnight oximetry in the diagnosis of sleep apnoea hypopnoea syndrome
Authors: J A BENNETT, W J M KINNEAR
Journal: Thorax (1999)

The obstructive sleep apnoea hypopnoea syndrome (SAHS) has been recognised for over 30 years and an effective treatment—namely, nasal continuous positive airway pressure (nCPAP)—has been available for almost 20 years. Research into SAHS has risen exponentially during this time, providing us with greater understanding of the epidemiology, pathophysiology, and morbidity associated with the disease. Despite this research, the most cost effective pathway for the diagnosis and management of SAHS has yet to be established and remains the subject of debate.

The gold standard diagnostic test for SAHS is overnight multichannel polysomnography (PSG) which enables detection of obstructive apnoeas, hypopnoeas, and arousals. However, PSG has several drawbacks. It is an expensive system to set up and run. The sleep laboratory is an artificial environment and some patients have a disturbed sleep pattern due to the foreign setting and thus interpretation of the PSG findings in these patients is problematic. The definition and quantification of apnoeas, hypopnoeas, and arousals remain subjects of debate.1-3 The apnoea hypopnoea index (AHI) increases in normal subjects with age, has moderate interobserver variation, and is poorly correlated with symptoms of excessive daytime somnolence.4 5 Thus, despite full PSG, identification of those patients with SAHS who benefit …
Thirty Years of HIV and AIDS: Future Challenges and Opportunities
Authors: Carl W. Dieffenbach, Anthony S. Fauci
Journal: Annals of Internal Medicine (2011)

As the third decade since AIDS was first recognized comes to an end, extraordinary advances have occurred in the understanding, treatment, and prevention of HIV infection and AIDS. As a result of these successes, it is now time to focus on future challenges. Paramount among these is reaching the goal of truly controlling and ultimately ending the HIV and AIDS pandemic. To that end, AIDS researchers and public health personnel worldwide are aggressively pursuing 3 key areas of scientific research. Given the availability of highly effective therapeutic regimens for HIV infection, the first challenge is efficiently identifying a maximum number of HIV-infected persons through voluntary HIV testing and initiating antiretroviral therapy (ART). Second, scientists are trying to develop a cure for HIV infection, which would alleviate the need for lifelong ART. Finally, preventing new cases of HIV infection, which currently number approximately 2.6 million per year globally, is critical to any attempt to end this pandemic. This article addresses each of these challenges and provides directions for the future.
Oral Magnesium Supplementation Improves Insulin Sensitivity and Metabolic Control in Type 2 Diabetic Subjects
Authors: Martha Rodríguez-Morán, Fernando Guerrero-Romero
Journal: Diabetes Care (2003)

OBJECTIVE—To determine whether oral magnesium supplementation (as magnesium chloride [MgCl2] solution) improves both insulin sensitivity and metabolic control in type 2 diabetic subjects with decreased serum magnesium levels. RESEARCH DESIGN AND METHODS—This study was a clinical randomized double-blind placebo-controlled trial. A total of 63 subjects with type 2 diabetes and decreased serum magnesium (serum magnesium levels ≤0.74 mmol/l) treated by glibenclamide received either 50 ml MgCl2 solution (containing 50 g MgCl2 per 1,000 ml solution) or placebo daily for 16 weeks. Chronic diarrhea, alcoholism, use of diuretic and/or calcium antagonist drugs, and reduced renal function were exclusion criteria. Homeostasis model assessment for insulin resistance (HOMA-IR) was used as the parameter of insulin sensitivity and glucose and HbA1c as parameters of metabolic control. RESULTS—At the end of the study, subjects who received magnesium supplementation showed significant higher serum magnesium concentration (0.74 ± 0.10 vs. 0.65 ± 0.07 mmol/l, P = 0.02) and lower HOMA-IR index (3.8 ± 1.1 vs. 5.0 ± 1.3, P = 0.005), fasting glucose levels (8.0 ± 2.4 vs. 10.3 ± 2.1 mmol/l, P = 0.01), and HbA1c (8.0 ± 2.4 vs. 10.1 ± 3.3%, P = 0.04) than control subjects. CONCLUSIONS—Oral supplementation with MgCl2 solution restores serum magnesium levels, improving insulin sensitivity and metabolic control in type 2 diabetic patients with decreased serum magnesium levels.
Abiraterone and Increased Survival in Metastatic Prostate Cancer
Authors: Johann S. de Bono, Christopher J. Logothetis, Arturo Molina, Karim Fizazi, Scott North, Luis Chu, Kim N. Chi, Robert J. Jones, Oscar B. Goodman, Fred Saad, John N. Staffurth, Paul Mainwaring, Stephen Harland, Thomas W. Flaig, Thomas E. Hutson, Tina Cheng, Helen Patterson, John D. Hainsworth, Charles J. Ryan, Cora N. Sternberg, Susan L. Ellard, Aude Fléchon, Mansoor Saleh, Mark Scholz, Eleni Efstathiou, Andrea Zivi, Diletta Bianchini, Yohann Loriot, Nicole Chieffo, Thian Kheoh, Christopher M. Haqq, Howard I. Scher
Journal: New England Journal of Medicine (2011)

Biosynthesis of extragonadal androgen may contribute to the progression of castration-resistant prostate cancer. We evaluated whether abiraterone acetate, an inhibitor of androgen biosynthesis, prolongs overall survival among patients with metastatic castration-resistant prostate cancer who have received chemotherapy.We randomly assigned, in a 2:1 ratio, 1195 patients who had previously received docetaxel to receive 5 mg of prednisone twice daily with either 1000 mg of abiraterone acetate (797 patients) or placebo (398 patients). The primary end point was overall survival. The secondary end points included time to prostate-specific antigen (PSA) progression (elevation in the PSA level according to prespecified criteria), progression-free survival according to radiologic findings based on prespecified criteria, and the PSA response rate.After a median follow-up of 12.8 months, overall survival was longer in the abiraterone acetate-prednisone group than in the placebo-prednisone group (14.8 months vs. 10.9 months; hazard ratio, 0.65; 95% confidence interval, 0.54 to 0.77; P<0.001). Data were unblinded at the interim analysis, since these results exceeded the preplanned criteria for study termination. All secondary end points, including time to PSA progression (10.2 vs. 6.6 months; P<0.001), progression-free survival (5.6 months vs. 3.6 months; P<0.001), and PSA response rate (29% vs. 6%, P<0.001), favored the treatment group. Mineralocorticoid-related adverse events, including fluid retention, hypertension, and hypokalemia, were more frequently reported in the abiraterone acetate-prednisone group than in the placebo-prednisone group.The inhibition of androgen biosynthesis by abiraterone acetate prolonged overall survival among patients with metastatic castration-resistant prostate cancer who previously received chemotherapy. (Funded by Cougar Biotechnology; COU-AA-301 ClinicalTrials.gov number, NCT00638690.).
External validation of blood eosinophils, FE<sub>NO</sub>and serum periostin as surrogates for sputum eosinophils in asthma
Authors: A H Wagener, S B de Nijs, R Lutter, A R Sousa, E J M Weersink, E H Bel, P J Sterk
Journal: Thorax (2014)

<h3>Background</h3> Monitoring sputum eosinophils in asthma predicts exacerbations and improves management of asthma. Thus far, blood eosinophils and FE<sub>NO</sub> show contradictory results in predicting eosinophilic airway inflammation. More recently, serum periostin was proposed as a novel biomarker for eosinophilic inflammation. <h3>Objectives</h3> Quantifying the mutual relationships of blood eosinophils, FE<sub>NO</sub>, and serum periostin with sputum eosinophils by external validation in two independent cohorts across various severities of asthma. <h3>Methods</h3> The first cohort consisted of 110 patients with mild to moderate asthma (external validation cohort). The replication cohort consisted of 37 patients with moderate to severe asthma. Both cohorts were evaluated cross-sectionally. Sputum was induced for the assessment of eosinophils. In parallel, blood eosinophil counts, serum periostin concentrations and FE<sub>NO</sub> were assessed. The diagnostic accuracy of these markers to identify eosinophilic asthma (sputum eosinophils ≥3%) was calculated using receiver operating characteristics area under the curve (ROC AUC). <h3>Results</h3> In the external validation cohort, ROC AUC for blood eosinophils was 89% (p&lt;0.001) and for FE<sub>NO</sub> level 78% (p&lt;0.001) to detect sputum eosinophilia ≥3%. Serum periostin was not able to distinguish eosinophilic from non-eosinophilic airway inflammation (ROC AUC=55%, p=0.44). When combining these three variables, no improvement was seen. The diagnostic value of blood eosinophils was confirmed in the replication cohort (ROC AUC 85%, p&lt;0.001). <h3>Conclusions</h3> In patients with mild to moderate asthma, as well as patients with more severe asthma, blood eosinophils had the highest accuracy in the identification of sputum eosinophilia in asthma. The use of blood eosinophils can facilitate individualised treatment and management of asthma. <h3>Trial registration</h3> NTR1846 and NTR2364.
Incremental Value of the Preoperative Echocardiogram to Predict Mortality and Major Morbidity in Coronary Artery Bypass Surgery
Authors: Jonathan Afilalo, Aidan W. Flynn, Avi Shimony, Lawrence G. Rudski, Arvind K. Agnihotri, Jean-Francois Morin, Cristina Castrillo, David M. Shahian, Michael H. Picard
Journal: Circulation (2012)

Although echocardiography is commonly performed before coronary artery bypass surgery, there has yet to be a study examining the incremental prognostic value of a complete echocardiogram.Patients undergoing isolated coronary artery bypass surgery at 2 hospitals were divided into derivation and validation cohorts. A panel of quantitative echocardiographic parameters was measured. Clinical variables were extracted from the Society of Thoracic Surgeons database. The primary outcome was in-hospital mortality or major morbidity, and the secondary outcome was long-term all-cause mortality. The derivation cohort consisted of 667 patients with a mean age of 67.2±11.1 years and 22.8% females. The following echocardiographic parameters were found to be optimal predictors of mortality or major morbidity: severe diastolic dysfunction, as evidenced by restrictive filling (odds ratio, 2.96; 95% confidence interval, 1.59-5.49), right ventricular dysfunction, as evidenced by fractional area change <35% (odds ratio, 3.03; 95% confidence interval, 1.28-7.20), or myocardial performance index >0.40 (odds ratio, 1.89; 95% confidence interval, 1.13-3.15). These results were confirmed in the validation cohort of 187 patients. When added to the Society of Thoracic Surgeons risk score, the echocardiographic parameters resulted in a net improvement in model discrimination and reclassification with a change in c-statistic from 0.68 to 0.73 and an integrated discrimination improvement of 5.9% (95% confidence interval, 2.8%-8.9%). In the Cox proportional hazards model, right ventricular dysfunction and pulmonary hypertension were independently predictive of mortality over 3.2 years of follow-up.Preoperative echocardiography, in particular right ventricular dysfunction and restrictive left ventricular filling, provides incremental prognostic value in identifying patients at higher risk of mortality or major morbidity after coronary artery bypass surgery.