tbuckley/cabot-search huggingface dataset:
Carcinoma of the bronchus: survival following conservative resection.
Authors: S J MacHale
Journal: Thorax (1966)

Atarax (hydroxyzine hydrochloride - Pfizer) was first marketed in 1956, at a time when different terms were competing to describe the drugs that in Britain eventually came to be called the tranquillisers. ‘Ataractics’ was one such term, and at that time ‘Atarax’ must have seemed a best-selling name. But it was never a very useful drug (‘It does not quieten angry animals. It is of dubious value in therapeutics’.<sup>1</sup>), and although it has continued to be available, it has not been marketed with especial vigour.
Cardiovascular Manifestations of HIV Infection
Authors: Giuseppe Barbaro
Journal: Circulation (2002)

S tudies published over the past 3 years have tracked the incidence and course of human immunodeficiency virus (HIV) infection in relation to cardiac illness in both children and adults. 1 These studies show that subclinical echocardiographic abnormalities independently predict adverse outcomes and identify high-risk groups to target for early intervention and therapy.The Joint United Nations Program on HIV/AIDS estimates that 36.1 million people were living with HIV infection at the end of the year 2000. 2 If 8% to 10% of patients develop symptomatic heart failure over a 2-to 5-year period, 3 then 3 million cases of HIV-related heart failure will present during that period. 1 Cardiovascular manifestations of HIV have been altered by the introduction of highly active antiretroviral therapy (HAART) regimens.On one hand, HAART has significantly modified the course of HIV disease, lengthened survival, and improved the quality of life of HIV-infected patients.On the other hand, the early data have raised concerns that HAART is associated with an increase in both peripheral and coronary arterial diseases. 1The HAART-associated changes are relevant only to the minority of HIV-infected individuals worldwide who have access to HAART.Thus, studies conducted before HAART became available remain globally applicable.In this review article, the principal HIV-associated cardiovascular manifestations will be discussed, with an emphasis on new knowledge about prevalence, pathogenesis, and treatment.
Smoke Without Fire: Most Reported Cases of Intron Gain in Nematodes Instead Reflect Intron Losses
Authors: S. W. Roy, D. Penny
Journal: Molecular Biology and Evolution (2006)

Identification of recently gained spliceosomal introns would provide crucial evidence in the continuing debate concerning the age and evolutionary significance of introns. A previously published genomic analysis reported to have identified 122 introns that had been gained since the divergence of the nematodes Caenorhabidits elegans and Caenorhabditis briggsae ∼100 MYA. However, using newly available genomic sequence from additional Caenorhabditis species, we show that 74% (60/81) of the reported gains in C. elegans are present in a C. briggsae relative. This pattern indicates that these introns represent losses in C. briggsae, not gains in C. elegans. In addition, 61% (25/41) of the reported gains in C. briggsae are present in the more distant C. briggsae relative, in a pattern suggesting that additional reported gains in C. elegans and/or C. briggsae may in fact represent unrecognized losses. These results underscore the dominance of intron loss over intron gain in recent eukaryotic evolution, the pitfalls associated with parsimony in inferring intron gains, and the importance of genomic sequencing of clusters of closely related species for drawing accurate inferences about genome evolution.
A consensus prognostic gene expression classifier for ER positive breast cancer.
Authors: Andrew E Teschendorff, Ali Naderi, Nuno L Barbosa-Morais, Sarah E Pinder, Ian O Ellis, Sam Aparicio, James D Brenton, Carlos Caldas
Journal: Genome biology (2006)

Abstract Background A consensus prognostic gene expression classifier is still elusive in heterogeneous diseases such as breast cancer. Results Here we perform a combined analysis of three major breast cancer microarray data sets to hone in on a universally valid prognostic molecular classifier in estrogen receptor (ER) positive tumors. Using a recently developed robust measure of prognostic separation, we further validate the prognostic classifier in three external independent cohorts, confirming the validity of our molecular classifier in a total of 877 ER positive samples. Furthermore, we find that molecular classifiers may not outperform classical prognostic indices but that they can be used in hybrid molecular-pathological classification schemes to improve prognostic separation. Conclusion The prognostic molecular classifier presented here is the first to be valid in over 877 ER positive breast cancer samples and across three different microarray platforms. Larger multi-institutional studies will be needed to fully determine the added prognostic value of molecular classifiers when combined with standard prognostic factors.
A Coccidioidomycosis Outbreak Following the Northridge, Calif, Earthquake
Authors: Eileen Schneider, Rana A. Hajjeh, Richard A. Spiegel, Randall W. Jibson, Edwin L. Harp, Grant A. Marshall, Robert A. Gunn, Michael M. McNeil, Robert W. Pinner, Roy C. Baron, Ronald C. Burger, Lori C. Hutwagner, Casey Crump, Leo Kaufman, Susan E. Reef, Gary M. Feldman, Demosthenes Pappagianis, S. Benson Werner
Journal: JAMA (1997)

To describe a coccidioidomycosis outbreak in Ventura County following the January 1994 earthquake, centered in Northridge, Calif, and to identify factors that increased the risk for acquiring acute coccidioidomycosis infection.Epidemic investigation, population-based skin test survey, and case-control study.Ventura County, California.In Ventura County, between January 24 and March 15, 1994, 203 outbreak-associated coccidioidomycosis cases, including 3 fatalities, were identified (attack rate [AR], 30 cases per 100,000 population). The majority of cases (56%) and the highest AR (114 per 100,000 population) occurred in the town of Simi Valley, a community located at the base of a mountain range that experienced numerous landslides associated with the earthquake. Disease onset for cases peaked 2 weeks after the earthquake. The AR was 2.8 times greater for persons 40 years of age and older than for younger persons (relative risk, 2.8; 95% confidence interval [CI], 2.1-3.7; P<.001). Environmental data indicated that large dust clouds, generated by landslides following the earthquake and strong aftershocks in the Santa Susana Mountains north of Simi Valley, were dispersed into nearby valleys by northeast winds. Simi Valley case-control study data indicated that physically being in a dust cloud (odds ratio, 3.0; 95% CI, 1.6-5.4; P<.001) and time spent in a dust cloud (P<.001) significantly increased the risk for being diagnosed with acute coccidioidomycosis.Both the location and timing of cases strongly suggest that the coccidioidomycosis outbreak in Ventura County was caused when arthrospores were spread in dust clouds generated by the earthquake. This is the first report of a coccidioidomycosis outbreak following an earthquake. Public and physician awareness, especially in endemic areas following similar dust cloud-generating events, may result in prevention and early recognition of acute coccidioidomycosis.
<i>Mixed Lineage Leukemia</i>–Rearranged Childhood Pro-B and CD10-Negative Pre-B Acute Lymphoblastic Leukemia Constitute a Distinct Clinical Entity
Authors: Andishe Attarbaschi, Georg Mann, Margit König, Manuel Steiner, Sabine Strehl, Anita Schreiberhuber, Björn Schneider, Claus Meyer, Rolf Marschalek, Arndt Borkhardt, Winfried F. Pickl, Thomas Lion, Helmut Gadner, Oskar A. Haas, Michael N. Dworzak
Journal: Clinical Cancer Research (2006)

Abstract Purpose:Mixed lineage leukemia (MLL) abnormalities occur in ∼50% of childhood pro-B acute lymphoblastic leukemia (ALL). However, the incidence and type of MLL rearrangements have not been determined in common ALL (cALL) and CD10+ or CD10− pre-B ALL. Experimental Design: To address this question, we analyzed 29 patients with pro-B ALL, 11 patients with CD10− pre-B ALL, 23 pre-B, and 26 cALL patients with CD10 on 20% to 80%, as well as 136 pre-B and 143 cALL patients with CD10 ≥80% of blasts. They were all enrolled in four Austrian ALL multicenter trials. Conventional cytogenetics were done to detect 11q23 abnormalities and in parallel the potential involvement of the MLL gene was evaluated with a split apart fluorescence in situ hybridization probe set. Results: We found that 15 of 29 pro-B ALL, 7 of 11 CD10− pre-B ALL, and 1 of 2 French-American-British classification L1 mature B-cell leukemia cases had a MLL rearrangement. However, no 11q23/MLL translocation was identified among the CD10+ pre-B and cALL patients. MLL-rearranged pro-B and CD10− pre-B ALL cases had similar clinical and immunophenotypic (coexpression of CDw65 and CD15) features at initial diagnosis. Conclusions: The striking similarities between the two CD10− ALL subsets imply that CD10− pre-B ALL variants may represent pro-B ALL cases that maintained the propensity to rearrange and express their immunoglobulin heavy chain rather than actual pre-B ALL forms transformed at this later stage of B-cell differentiation. However, direct experimental data are needed to confirm this observation.
Fludarabine, mitoxantrone, dexamethasone (FND) compared with an alternating triple therapy (ATT) regimen in patients with stage IV indolent lymphoma
Authors: Apostolia M. Tsimberidou, Peter McLaughlin, Anas Younes, Maria A. Rodriguez, Fredrick B. Hagemeister, Andreas Sarris, Jorge Romaguera, Mark Hess, Terry L. Smith, Ying Yang, Ana Ayala, Alejandro Preti, Ming-Sheng Lee, Fernando Cabanillas
Journal: Blood (2002)
A Phase I Trial of a Human Papillomavirus DNA Vaccine for HPV16+ Cervical Intraepithelial Neoplasia 2/3
Authors: Cornelia L. Trimble, Shiwen Peng, Ferdynand Kos, Patti Gravitt, Raphael Viscidi, Elizabeth Sugar, Drew Pardoll, T.C. Wu
Journal: Clinical Cancer Research (2008)

Abstract Purpose: To evaluate the safety and immunogenicity of a therapeutic human papillomavirus (HPV)16 DNA vaccine administered to women with HPV16+cervical intraepithelial neoplasia (CIN)2/3. Experimental Design: This phase I trial incorporated the standard ′3+3″ dose-escalation design with an additional 6 patients allocated to the maximally tolerated dose. Healthy adult women with colposcopically directed, biopsy-proven HPV16+ CIN2/3 received 3 i.m. vaccinations (0.5, 1, or 3 mg) of a plasmid expressing a Sig-E7(detox)-heat shock protein 70 fusion protein on days 0, 28, and 56, and underwent standard therapeutic resection of the cervical squamocolumnar junction at day 105 (week 15). The safety and immunogenicity of the vaccine and histologic outcome based on resection at week 15 were assessed. Results: Fifteen patients were evaluable (3 each at 0.5 and 1mg, 9 at 3 mg). The vaccine was well tolerated: most adverse events were mild, transient injection-site discomfort; no dose-limiting toxicities were observed. Although HPVE7-specific T-cell responses to E7 detected by enzyme-linked immunospot assays (IFN-γ) were of low frequency and magnitude, detectable increases in response subsequent to vaccination were identified in subjects in the second and third cohorts. Complete histologic regression occurred in 3 of 9 (33%; 7-70% confidence interval) individuals in the highest-dose cohort. Although the difference is not significant, it is slightly higher than would be expected in an unvaccinated cohort (25%). Conclusions: This HPV16 DNA vaccine was safe and well tolerated. Whereas it seems possible to elicit HPV-specific T-cell responses in patients with established dysplastic lesions, other factors are likely to play a role in lesion regression.
Developmental Demands of Cognitive Behavioral Therapy for Depression in Children and Adolescents: Cognitive, Social, and Emotional Processes
Authors: Judy Garber, Sarah A. Frankel, Catherine G. Herrington
Journal: Annual Review of Clinical Psychology (2016)

Although some treatments for depression in children and adolescents have been found to be efficacious, the effects sizes have tended to be modest. Thus, there is considerable room to improve upon existing depression treatments. Some children may respond poorly because they do not yet have the cognitive, social, or emotional maturity needed to understand and apply the skills being taught in therapy. Therefore, treatments for depression may need to be tailored to match children's ability to both comprehend and implement the therapeutic techniques. This review outlines the steps needed for such developmental tailoring: (a) Specify the skills being taught in depression treatments; (b) identify what cognitive, social, and emotional developmental abilities are needed to attain these skills; (c) describe the normative developmental course of these skills and how to determine a child's developmental level; and (d) use this information to design an individualized treatment plan. Possible approaches to intervening include: alter the therapy to meet the child's level of development, train the child on the skills needed to engage in the therapy, or apply a dynamic assessment approach that integrates evaluation into treatment and measures children's current abilities as well as their potential.
Mechanism of <i>In vitro</i> Pancreatic Cancer Cell Growth Inhibition by Melanoma Differentiation–Associated Gene-7/Interleukin-24 and Perillyl Alcohol
Authors: Irina V. Lebedeva, Zhao-zhong Su, Nichollaq Vozhilla, Lejuan Chatman, Devanand Sarkar, Paul Dent, Mohammad Athar, Paul B. Fisher
Journal: Cancer Research (2008)

The death rate for pancreatic cancer approximates the number of new cases each year, and when diagnosed, current therapeutic regimens provide little benefit in extending patient survival. These dire statistics necessitate the development of enhanced single or combinatorial therapies to decrease the pathogenesis of this invariably fatal disease. Melanoma differentiation-associated gene-7/interleukin-24 (mda-7/IL-24) is a potent cancer gene therapeutic because of its broad-spectrum cancer-specific apoptosis-inducing properties as well as its multipronged indirect antitumor activities. However, pancreatic cancer cells show inherent resistance to mda-7/IL-24 that is caused by a block of translation of mda-7/IL-24 mRNA in these tumor cells. We now reveal that a dietary agent perillyl alcohol (POH) in combination with Ad.mda-7 efficiently reverses the mda-7/IL-24 "protein translational block" by inducing reactive oxygen species, thereby resulting in mda-7/IL-24 protein production, growth suppression, and apoptosis. Pharmacologic inhibitor and small interfering RNA studies identify xanthine oxidase as a major source of superoxide radical production causing these toxic effects. Because both POH and Ad.mda-7 are being evaluated in clinical trials, combining a dietary agent and a virally delivered therapeutic cytokine provides an innovative approach for potentially treating human pancreatic cancer.
Regional changes in hemodynamics and cardiac myocyte size in rats with aortocaval fistulas. 2. Long-term effects.
Authors: Z Liu, D R Hilbelink, A M Gerdes
Journal: Circulation Research (1991)

Regional changes in hemodynamics and cardiac myocyte size were examined in adult rats 5 months after creating a large aortocaval fistula. At that time, cardiac output, left and right ventricular pressures, and left and right ventricular dP/dtmax were measured. Subsequently, isolated cardiac myocytes were collected from the left ventricle, right ventricle, and septum for cell size measurements. Compared with sham-operated controls, percent dry weight was reduced in the liver and kidney but was unchanged in the lung. Heart rate, left ventricular systolic pressure, left ventricular dP/dtmax, and systolic aortic pressure were not changed in rats with fistulas. However, cardiac output, stroke volume, left ventricular end-diastolic pressure, and all measured parameters in the right ventricle were significantly increased. Mean cell volume and the ratio of heart weight to body weight were both elevated 92%. Cell volume, cell length, and cross-sectional area increased significantly in each heart region examined. Hypertrophy was more pronounced in cells from the right ventricle and the endomyocardium of the left ventricle. The percentage of cells with mononucleation or binucleation was not changed in any heart region of rats with fistulas. In summary, despite evidence of renal and hepatic congestion, most indexes of cardiac function were normal or elevated 5 months after creation of a large volume-overload-induced hypertrophy. Data from isolated cardiac myocytes suggested that cellular hypertrophy, rather than hyperplasia, was responsible for the increased cardiac mass.
A novel immune regulator links malaria and inflammatory bowel disease
Authors: Brandon K. Sack, Stefan H. Kappe
Journal: The Journal of Experimental Medicine (2014)

The Journal of Experimental Medicine Malaria is caused by Plasmodium parasites and is commonly thought of as a disease resulting from the cyclic infection and destruction of red blood cells.However, a subset of infected individuals will develop "cerebral malaria"-a pathogenic neuroinflammation, presumably caused by parasitized red blood cells sequestering in the brain.Those affected, usually children under the age of five, can die or suffer permanent cognitive impairment long after successful treatment of infection.The exact causes of cerebral malaria are poorly understood, but mouse models of experimental cerebral malaria have identified CD8 + T cells as key players in the development of this debilitating condition.In this issue, Kennedy et al. used an unbiased genome-wide screen of ENU-mutagenized mice to identify a novel gene, Ccdc88b, that influences T cell activation and function and that is associated with resistance to cerebral malaria following infection with the mouse malaria parasite Plasmodium berghei.They found Ccdc88b to be expressed in T cells and myeloid cells.T cells from Ccdc88b / knockout mice were impaired in their ability to become activated and to secrete effector cytokines in response to stimulation via their T cell receptor.Importantly, unlike T cells from wild-type mice, adoptive transfer of T cells from knockout mice did not confer cerebral malaria to recipient mice.With over 300 million malaria infections each year, cerebral malaria causes substantial mortality.Understanding the molecular and cellular etiology of cerebral malaria will lead to better identification and treatment of those most at risk.Furthermore, CD8 + T cells have a duplicitous role in malaria infection-both helping to clear the parasite from the liver and blood and in orchestrating the damaging neuroinflammation seen in cerebral malaria.Understanding the events leading to a pathogenic T cell response could also help inform the design of malaria vaccines that eliminate, but do not exacerbate, disease.The authors' work also extends beyond models of malaria, as a region in the human genome that contains Ccdc88b has been implicated in autoimmune disorders such as inflammatory bowel disease, multiple sclerosis, and Crohn's disease.This further supports the idea that Ccdc88b is a novel and important regulator of immune function.It will be fascinating to confirm the role of Ccdc88b in other immune disease models and to determine whether this pathway could be manipulated to quell overzealous T cells in malaria pathogenesis and beyond.
Caution Should Be Used When Interpreting Alterations Affecting the Exon 3 of the <i>BRCA2</i> Gene in Breast/Ovarian Cancer Families
Authors: Orland Díez, Sara Gutiérrez-Enríquez, Teresa Ramón y Cajal, Carmen Alonso, Judith Balmaña, Gemma Llort
Journal: Journal of Clinical Oncology (2007)
Internists' Practices in Health Promotion and Disease Prevention
Authors: J. Sanford Schwartz, Charles E. Lewis, Carolyn Clancy, Monica S. Kinosian, Margaret H. Radany, Jeffrey P. Koplan
Journal: Annals of Internal Medicine (1991)

Objective: To estimate internists' use of disease prevention and health promotion activities, and to explore demographic, professional, behavioral, psychological, cognitive, and organizational factors associated with the use of such practices. Design: Mail survey. Setting and Subjects: A sample of 2610 members and fellows of the American College of Physicians (ACP) participated in the study. They engaged in patient care activities more than 20 hours per week and were stratified by gender and region. They lived in four geographic areas of the United States (Northeast, Southeast, Central, and West), comprising 21 ACP regions. Measurements: A questionnaire requesting background information as well as information about personal health; record keeping; use of immunizations (pneumococcal, influenza, tetanus, hepatitis B); use of screening tests and procedures for detecting cancer (breast examination, Papanicolaou smear, stool occult blood test) and other diseases (electrocardiograms, cholesterol level tests, chest radiographs); and behavioral counseling to promote health (in the areas of smoking, exercise, and alcohol and seat belt use). Main Results: Internists used effective preventive interventions less frequently and ineffective practices more frequently than experts recommend. Internists' use of health promotion and disease prevention activities is associated with habit, attitude, and a lack of adequate knowledge. Younger physician age, general internal medicine practice, and personal health promotion and disease prevention practices were strongly associated with more appropriate use of recommended practices (P < 0.01). Conclusions: Internists' use of disease prevention and health promotion activities falls short of expert recommendations. Programs to improve the delivery of preventive services might be aimed at improving physicians' personal health practices, might be directed toward patients, and might include the development of effective systems to remind physicians.
Characterisation of patients with a complete biochemical response to ursodeoxycholic acid.
Authors: R A Jorgensen, E R Dickson, A F Hofmann, S S Rossi, K D Lindor
Journal: Gut (1995)

Ursodeoxycholic acid (UDCA) leads to biochemical and clinical improvement in many patients with primary biliary cirrhosis (PBC); although, the response is variable. This study compared UDCA treated patients with complete normalisation of biochemical functions to those without such improvement. Of the 65 patients receiving UDCA, 12 (19%) showed normalisation of liver biochemical functions at two years. The remaining 53 patients showed a less complete response. Mean (SD) alkaline phosphatase and total serum bilirubin values were significantly lower at entry in the patients whose liver biochemistry tests normalised (912 (732) U/l v 1417 (1021) U/l, p = 0.003, and 0.7 (12.1 (5.2) mumol/l v 38.9 (48.5) mumol/l, p = 0.0002, respectively), and percentage of UDCA in biliary bile acid was higher (56.3 (9.5)% v 38.3 (21.1)%, p = 0.03). Patients with biochemically and histologically less severe disease, and greater enrichment of biliary bile with UDCA, are more likely to respond favourably to the drug. The main objective of continued study will be to find out if normal liver biochemical functions can retard disease progression. The association of greater UDCA enrichment with complete biochemical responses suggests that higher doses of UDCA should be evaluated.
Medicines for children in Europe: from proposals to practicalities
Authors: A. Bush, M. Zach
Journal: European Respiratory Journal (2009)

Where then are we going, and how far have we got?It is clear that new initiatives in medicines for children represent a oncein-a-career opportunity.We need the reality of truly evidencebased therapy for children, not merely in common conditions, but also in rarities.The hope is that the current ERS and EAP initiatives will help to move this important field forward in a good way for children.