tbuckley/cabot-search huggingface dataset:
Cross-National Epidemiology of Major Depression and Bipolar Disorder
Authors: Myrna M. Weissman
Journal: JAMA (1996)

To estimate the rates and patterns of major depression and bipolar disorder based on cross-national epidemiologic surveys.Population-based epidemiologic studies using similar methods from 10 countries: the United States, Canada, Puerto Rico, France, West Germany, Italy, Lebanon, Taiwan, Korea, and New Zealand.Approximately 38000 community subjects.Rates, demographics, and age at onset of major depression and bipolar disorder. Symptom profiles, comorbidity, and marital status with major depression.The lifetime rates for major depression vary widely across countries, ranging from 1.5 cases per 100 adults in the sample in Taiwan to 19.0 cases per 100 adults in Beirut. The annual rates ranged from 0.8 cases per 100 adults in Taiwan to 5.8 cases per 100 adults in New Zealand. The mean age at onset shows less variation (range, 24.8-34.8 years). In every country, the rates of major depression were higher for women than men. By contrast, the lifetime rates of bipolar disorder are more consistent across countries (0.3/100 in Taiwan to 1.5/100 in New Zealand); the sex ratios are nearly equal; and the age at first onset is earlier (average, 6 years) than the onset of major depression. Insomnia and loss of energy occurred in most persons with major depression at each site. Persons with major depression were also at increased risk for comorbidity with substance abuse and anxiety disorders at all sites. Persons who were separated or divorced had significantly higher rates of major depression than married persons in most of the countries, and the risk was somewhat greater for divorced or separated men than women in most countries.There are striking similarities across countries in patterns of major depression and of bipolar disorder. The differences in rates for major depression across countries suggest that cultural differences or different risk factors affect the expression of the disorder.
Electrophilic nitro-fatty acids inhibit vascular inflammation by disrupting LPS-dependent TLR4 signalling in lipid rafts
Authors: Luis Villacorta, Lin Chang, Sonia R. Salvatore, Tomonaga Ichikawa, Jifeng Zhang, Danica Petrovic-Djergovic, Lingyun Jia, Harald Carlsen, Francisco J. Schopfer, Bruce A. Freeman, Y. Eugene Chen
Journal: Cardiovascular Research (2013)

AimsElectrophilic fatty acid nitroalkene derivatives, products of unsaturated fatty acid nitration, exert long-term cardiovascular protection in experimental models of metabolic and cardiovascular diseases. The goal of this study is to examine the effects of nitro-fatty acids in the regulation of upstream signalling events in nuclear factor-κB (NF-κB) activation and determine whether low-dose acute administration of nitro-fatty acids reduces vascular inflammation in vivo.
Effect of acute L-arginine supplementation on 20 km time trial performance in competitive male cyclists
Authors: M K Ranchordas, T Whitehead
Journal: British Journal of Sports Medicine (2011)

Increasing literature has studied the effects of dietary nitrates and moreover, L-arginine supplementation on tolerance to exercise and O 2 consumption during exercise. However, few studies have investigated the effects of L-arginine on performance measures such as a time trial. It was hypothesised that an acute 3-day L-arginine supplementation would elicit a significant improvement in performance and reduce oxygen consumption during a 20 km time trial. 6 healthy male competitive cyclists (23 ± 5 y) participated in a double-blind crossover study, and consumed either one 500 m placebo (PLA) or L-arginine (ARG) beverage, containing 6 g of L-arginine, over a 2 week testing period. Following a 3-day supplementation, participants completed a ramped incremental test to exhaustion, followed by an hours rest and subsequently a 20 km time trial. Time trial completion time was reduced by 34 s (PLA 32:38 ± 1:50 vs ARG 32:04 ± 1:38 min, P &lt;0.05), O 2 consumption during the time trial was also reduced (PLA 51.6 ± 8.2 vs ARG 47.5 ± 6.1 mL . kg . min -1 , P &lt;0.05). Furthermore, both systolic and diastolic blood pressure were greatly reduced (PLA 132 ± 7 vs ARG 127 ± 7 mm Hg P &lt;0.05 and PLA 79 ± 5 vs ARG 74 ± 5 mm Hg respectively, P &lt;0.05). However, no differences were seen in participants' VO 2 max during the ramped incremental test to exhaustion (58 ± 8 vs 58 ± 8 ml . kg . min -1 , P &gt;0.05) although W peak was higher during the same test (PLA 385 ± 38 vs ARG 395 ± 39 W). In conclusion, acute 3-day L-arginine supplementation at a dose of 6 g . day -1 increases 20 km time trial performance and reduces O 2 consumption during time trial performance, in addition to reducing systolic and diastolic blood pressure. However, L-arginine appears to have no effect upon VO 2 max
Enrollment Update of the Epidemiologic Study of Xolair: Evaluating the Long-Term Safety and Clinical Effectiveness in Patients with Moderate to Severe Asthma (EXCELS)
Authors: M.K. Miller, J.H. Lee, D. Forer, A. Vaghar, E. Israel, M. Kraft, F. Martinez, D. Miller, G. Shaprio, R. Tarone, S. Szefler
Journal: Journal of Allergy and Clinical Immunology (2006)
A Phase 1 Escalating Single-Dose and Weekly Fixed-Dose Study of Cetuximab: Pharmacokinetic and Pharmacodynamic Rationale for Dosing
Authors: Paula M. Fracasso, Howard Burris, Matthew A. Arquette, Ramaswamy Govindan, Feng Gao, Lisa P. Wright, Sherry A. Goodner, F. Anthony Greco, Suzanne F. Jones, Noel Willcut, Catherine Chodkiewicz, Amit Pathak, Gregory M. Springett, George R. Simon, Daniel M. Sullivan, Raphaël Marcelpoil, Shelley D. Mayfield, David Mauro, Christopher R. Garrett
Journal: Clinical Cancer Research (2007)

This phase 1 study evaluated the pharmacokinetic and pharmacodynamic effects of cetuximab on patients with epithelial malignancies.Following a skin and tumor biopsy, patients with advanced epithelial malignancies were randomized to receive a single dose of cetuximab at 50, 100, 250, 400, or 500 mg/m2 i.v. Repeat skin (days 2, 8, 15, and 22) and tumor (day 8) biopsies were obtained. Immunohistochemical expression of epidermal growth factor receptor (EGFR) and its pathway members was done on biopsies. Blood samples were obtained over 22 days for pharmacokinetic analyses. After day 22, all patients received weekly 250 mg/m2 cetuximab until disease progression or unacceptable toxicity.Thirty-nine patients enrolled. Rash was noted in 26 (67%) patients. Three patients (two with colon cancer and one with laryngeal cancer) achieved a partial response and 13 patients had stable disease. Pharmacokinetic data revealed mean maximum observed cetuximab concentrations and mean area under the concentration-time curve from time zero to infinity increased in a dose-dependent manner up to 400 mg/m2 cetuximab. Mean clearance was similar at cetuximab doses>or=100 mg/m2, supporting saturation of EGFR binding at 250 mg/m2. Pharmacodynamic evaluation revealed that patients with partial response/stable disease had a higher-grade rash and higher cetuximab trough levels than those with progressive disease (P=0.032 and 0.002, respectively). Administration of single doses (250-500 mg/m2) of cetuximab resulted in a dose-dependent decrease in EGFR protein expression levels in skin over time, supporting a minimal dose of cetuximab at 250 mg/m2 for a pharmacodynamic effect.This study provides a pharmacokinetic and pharmacodynamic rationale for the dosing of cetuximab.
URBAN HEALTH: Evidence, Challenges, and Directions
Authors: Sandro Galea, David Vlahov
Journal: Annual Review of Public Health (2004)

Urbanization is one of the most important demographic shifts worldwide during the past century and represents a substantial change from how most of the world's population has lived for the past several thousand years. The study of urban health considers how characteristics of the urban environment may affect population health. This paper reviews the empirical research assessing urban living's impact on population health and our rationale for considering the study of urban health as a distinct field of inquiry. The key factors affecting health in cities can be considered within three broad themes: the physical environment, the social environment, and access to health and social services. The methodologic and conceptual challenges facing the study of urban health, arising both from the limitations of the research to date and from the complexities inherent in assessing the relations among complex urban systems, disease causation, and health are discussed.
Randomised controlled trials for Ebola: practical and ethical issues
Authors: Clement Adebamowo, Oumou Bah-Sow, Fred Binka, Roberto Bruzzone, Arthur Caplan, Jean-François Delfraissy, David Heymann, Peter Horby, Pontiano Kaleebu, Jean-Jacques Muyembe Tamfum, Piero Olliaro, Peter Piot, Abdul Tejan-Cole, Oyewale Tomori, Aissatou Toure, Els Torreele, John Whitehead
Journal: The Lancet (2014)
A phase 1 clinical trial of nerve growth factor gene therapy for Alzheimer disease
Authors: Mark H Tuszynski, Leon Thal, Mary Pay, David P Salmon, Hoi Sang U, Roy Bakay, Piyush Patel, Armin Blesch, H Lee Vahlsing, Gilbert Ho, Gang Tong, Steven G Potkin, James Fallon, Lawrence Hansen, Elliott J Mufson, Jeffrey H Kordower, Christine Gall, James Conner
Journal: Nature Medicine (2005)
Keratinocyte growth factor and the transcription factors C/EBPα, C/EBPδ, and SREBP-1c regulate fatty acid synthesis in alveolar type II cells
Authors: Robert J. Mason, Tianli Pan, Karen E. Edeen, Larry D. Nielsen, Feijie Zhang, Malinda Longphre, Michael R. Eckart, Steven Neben
Journal: Journal of Clinical Investigation (2003)

Strategies to stimulate endogenous surfactant production require a detailed understanding of the regulation of lipogenesis in alveolar type II cells. We developed culture conditions in which keratinocyte growth factor (KGF) stimulates fatty acid and phospholipid synthesis. KGF stimulated acetate incorporation into phosphatidylcholine, disaturated phosphatidylcholin, and phosphatidylglycerol more than 5% rat serum alone. To determine the mRNA levels of lipogenic enzymes and transport proteins, we analyzed gene expression by oligonucleotide microarrays. KGF increased the mRNA levels for fatty acid synthase, stearoyl-CoA desaturase-1 (SCD-1), and epidermal fatty acid–binding protein more than rat serum alone. In addition, KGF increased the mRNA levels of the transcription factors CCAAT/enhancer-binding protein α (C/EBPα) and C/EBPδ as well as SREBP-1c (ADD-1), but not PPARγ. These changes in C/EBPα and C/EBPδ were confirmed by in situ hybridization. SCD-1 was also found to be highly expressed in alveolar type II cells in vivo. Furthermore, KGF increased protein levels of fatty acid synthase, C/EBPα, C/EBPδ, SREBP-1, epidermal fatty acid–binding protein, and SCD. Finally, the liver X receptor agonist T0901317 increased acetate incorporation and SREBP-1 but not SREBP-2 protein levels. In summary, KGF stimulates lipogenesis in type II cells by a coordinated expression of lipogenic enzymes and transport proteins regulated by C/EBP isoforms and SREBP-1c.
Aspirin Use, 8q24 Single Nucleotide Polymorphism rs6983267, and Colorectal Cancer According to CTNNB1 Alterations
Authors: Hongmei Nan, Teppei Morikawa, Miia Suuriniemi, Yu Imamura, Lillian Werner, Aya Kuchiba, Mai Yamauchi, David J. Hunter, Peter Kraft, Edward L. Giovannucci, Charles S. Fuchs, Shuji Ogino, Matthew L. Freedman, Andrew T. Chan
Journal: JNCI Journal of the National Cancer Institute (2013)

Regular aspirin use reduces the risk for colorectal cancer (CRC), possibly through inhibition of WNT/cadherin-associated protein β1 (CTNNB1 or β-catenin) signaling. The single nucleotide polymorphism (SNP) rs6983267 on chromosome 8q24 is a CRC susceptibility locus that affects binding activity of transcription factor 7 like-2 (TCF7L2) to CTNNB1, thereby altering expression of target oncogenes, including MYC . We evaluated regular aspirin use and CRC risk according to genotypes of SNP rs6983267 and CTNNB1 expression status in two prospective case–control studies (840 CRC case patients and 1686 age- and race-matched control subjects) nested within the Nurses' Health Study and the Health Professionals Follow-up Study. We estimated odds ratios (ORs) and 95% confidence intervals (CIs) using unconditional logistic regression models. All statistical tests were two-sided. A lower risk of CRC was associated with regular aspirin use and the T allele of rs6983267. The effect of aspirin was confined to individuals with protective T allele of rs6983267 (additive matching factors–adjusted OR for T allele = 0.83; 95% CI = 0.74 to 0.94; Ptrend = .002; Pinteraction = .01). Additionally, the T allele of rs6983267 was associated with a reduced expression of MYC oncogene ( Ptrend = .03). Moreover, among individuals with protective T allele, the effect of regular aspirin use was limited to those with positive nuclear CTNNB1 expression. In a functional analysis, in vitro treatment of LS174T cells (a cell line heterozygous for rs6983267) with aspirin was statistically significantly associated with higher G/T allelic ratio of TCF7L2 immunoprecipitated DNA ( P = .03). Our results support an influence of aspirin on WNT/CTNNB1 signaling and suggest that aspirin chemoprevention may be tailored according to rs6983267 genotype.
Report on Infection and Immunity
Authors: G. E. C. Wood
Journal: BMJ (1896)

INFECTION AND IMMUNITY.[L hUL Jo8N 833 the case, however, the period of convalescence is fraught with considerable danger to life, and even in the most favourable cases is often protracted for several months and not infrequently marked by serious relapses.Thus f find that among ioo consecutive cases of chronic gastro-intestinal catarrh in infants which have come under my care at the Evelina Hospital and elsewhere, no fewer than 24 died after the symptoms of the primary disease had appaxently subsided.Of this number I3 succumbed to an attack of whooping-cough (g) or measles (4), 6 died either from broncho-pneumonia or tuberculosis, while the remaining 5 were subsequently attacked by acute intestinal catarrh, which proved rapidly fatal.
Report of a workshop: quantitative computed tomography scanning in longitudinal studies of emphysema
Authors: J.D. Newell, J.C. Hogg, G.L. Snider
Journal: European Respiratory Journal (2004)

It has been reported that quantitative computed tomography (CT) scanning of the lungs showed decreased progression of emphysema in a randomised clinical trial in patients with severe α<sub>1</sub>‐antitrypsin (α<sub>1</sub>‐AT) deficiency receiving monthly intravenous augmentation therapy with human α<sub>1</sub>‐AT. Comparable results were not obtained using rate of decline of forced expiratory volume in one second. Accordingly, the Alpha‐1 Foundation convened a workshop to explore the feasibility of using quantitative CT data as a primary outcome variable in trials of drugs for treating α<sub>1</sub>‐AT deficiency. This report reviews the following: the principles for the use of modern CT scanners for quantifying emphysema; the methods and data on validation by comparison with measurements of severity of emphysema in inflation-fixed specimens of lungs; and the possibility of decreasing radiation dosage from CT to make it safe and ethically possible to use CT in longitudinal studies. The workshop concluded that it is feasible, safe and ethically possible to use computed tomography in longitudinal studies of emphysema. It recommended that the primary end-point should be a significant shift in the 15th percentile of lung density.
Yield of Screening for Long-Term Complications Using the Children's Oncology Group Long-Term Follow-Up Guidelines
Authors: Wendy Landier, Saro H. Armenian, Jin Lee, Ola Thomas, F. Lennie Wong, Liton Francisco, Claudia Herrera, Clare Kasper, Karla D. Wilson, Meghan Zomorodi, Smita Bhatia
Journal: Journal of Clinical Oncology (2012)

The Children's Oncology Group Long-Term Follow-Up (COG-LTFU) Guidelines use consensus-based recommendations for exposure-driven, risk-based screening for early detection of long-term complications in childhood cancer survivors. However, the yield from these recommendations is not known.Survivors underwent COG-LTFU Guideline-directed screening. Yield was classified as negligible/negative (< 1%), intermediate (≥ 1% to < 10%), or high (≥ 10%). For long-term complications with high yield, logistic regression was used to identify subgroups more likely to screen positive.Over the course of 1,188 clinic visits, 370 childhood cancer survivors (53% male; 47% Hispanic; 69% leukemia/lymphoma survivors; median age at diagnosis, 11.1 years [range, 0.3 to 21.9 years]; time from diagnosis, 10.5 years [range, 5 to 55.8 years]) underwent 4,992 screening tests. High-yield tests included thyroid function (hypothyroidism, 10.1%), audiometry (hearing loss, 22.6%), dual-energy x-ray absorptiometry scans (low bone mineral density [BMD], 23.2%), serum ferritin (iron overload, 24.0%), and pulmonary function testing/chest x-ray (pulmonary dysfunction, 84.1%). Regression analysis failed to identify subgroups more likely to result in high screening yield, with the exception of low BMD (2.5-fold increased risk for males [P = .04]; 3.3-fold increased risk for nonobese survivors [P = .01]). Screening tests with negligible/negative (< 1%) yield included complete blood counts (therapy-related leukemia), dipstick urinalysis for proteinuria and serum blood urea nitrogen/creatinine (glomerular defects), microscopic urinalysis for hematuria (hemorrhagic cystitis, bladder cancer), ECG (anthracycline-related conduction disorder), and hepatitis B and HIV serology.Screening tests with a high yield are appropriate for risk groups targeted for screening by the COG-LTFU Guidelines. Elimination of screening tests with negligible/negative yield should be given consideration.
Natural killer cell stimulatory factor (interleukin 12 [IL-12]) induces T helper type 1 (Th1)-specific immune responses and inhibits the development of IL-4-producing Th cells.
Authors: R Manetti, P Parronchi, M G Giudizi, M P Piccinni, E Maggi, G Trinchieri, S Romagnani
Journal: The Journal of Experimental Medicine (1993)

The effects exerted on the in vitro development of antigen-specific T cell lines and T cell clones by addition or neutralization of interleukin 12 (IL-12) in lymphocyte bulk culture were examined. T cell lines specific for Dermatophagoides pteronyssinus group I (Der p I) derived in the presence of IL-12 exhibited reduced ability to produce IL-4 and increased ability to produce interferon gamma (IFN-gamma), and developed into Der p I-specific CD4+ T cell clones showing a T helper type 0 (Th0)- or Th1-, instead of Th2-, like cytokine profile. In contrast, purified protein derivative (PPD)-specific T cell lines derived in the presence of anti-IL-12 antibody exhibited an increased ability to produce IL-4 and developed into PPD-specific CD4+ T cell clones showing a Th0-, instead of Th1-, like profile. The influence of IL-12 on the cytokine secretion profile of Der p I-specific T cell lines was not prevented by addition to lymphocyte bulk cultures of anti-IFN-gamma antibody, but could be at least partially inhibited by the removal from bulk cultures of CD16+ cells. Thus, IL-12 and CD16+ cells appear to have inhibitory effects on the development of IL-4-producing cells and to play an inductive role in promoting Th1-like responses.
Length dependence of activation studied in the isovolumic blood-perfused dog heart.
Authors: P J Tucci, E A Bregagnollo, J Spadaro, A C Cicogna, M C Ribeiro
Journal: Circulation Research (1984)

In studies utilizing the isolated isovolumic blood-perfused canine heart, left ventricular pressure was measured following a sudden expansion of ventricular volume. An increase in performance occurred in two phases: first, there was an instantaneous rise of developed pressure simultaneous with ventricular distension; in the second phase, developed pressure continued to increase for several minutes until a final steady state was reached. The immediate increase in developed pressure occurred with a prolongation of the time-to-peak pressure, and there was no further change of time-to-peak pressure during the time-dependent increase of developed pressure. In another series of experiments, systolic pressure was elevated without changing resting volume, and mechanical performance changed in a different manner: after an increase in systolic load, there was a modest and transient decrease of developed pressure; thereafter, ventricular pressure recovered only to original values. The influence of different degrees of ventricular expansion, calcium, and verapamil were studied. Under higher ventricular dilations the immediate as well as the slow increase of contraction were heightened and the time to reach half of the slow increase was shortened. When ventricular dilation was induced during an infusion of calcium chloride, higher values for the immediate pressure increase were observed, whereas the time-dependent increase and the time to reach half of the slow increase did not change in comparison with control studies. Verapamil decreased the immediate and the time-dependent enhancement of contraction. The time-dependent increase in developed pressure occurs more slowly with verapamil.(ABSTRACT TRUNCATED AT 250 WORDS)
Treatment of Isolated Systolic Hypertension Is Most Effective in Older Patients With High-Risk Profile
Authors: Luigi Ferrucci, Curt D. Furberg, Brenda W.J.H. Penninx, Mauro DiBari, Jeff D. Williamson, Jack M. Guralnik, John G. Chen, William B. Applegate, Marco Pahor
Journal: Circulation (2001)

Although present guidelines suggest that treatment of hypertension is more effective in patients with multiple risk factors and higher risk of cardiovascular events, this hypothesis was never verified in older patients with systolic hypertension.Using data from the Systolic Hypertension in the Elderly Program, we calculated the global cardiovascular risk score according to the American Heart Association Multiple Risk Factor Assessment Equation in 4,189 participants free of cardiovascular disease (CVD) and in 264 participants with CVD at baseline. In the placebo group, rates of cardiovascular events over 4.5 years were progressively higher according to higher quartiles of CVD risk. The protection conferred by treatment was similar across quartiles of risk. However, the numbers needed to treat (NNTs) to prevent one cardiovascular event were progressively smaller according to higher cardiovascular risk quartiles. In participants with baseline CVD, the NNTs to prevent one cardiovascular event were similar to those estimated for CVD-free participants in the highest-risk quartile.Treatment of systolic hypertension is most effective in older patients who, because of additional risk factors or prevalent CVD, are at higher risk of developing a cardiovascular event. These patients are prime candidates for antihypertensive treatment.
Suicide Risk Among Soldiers
Authors: Matthew J. Friedman
Journal: JAMA Psychiatry (2014)

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