tbuckley/cabot-search huggingface dataset:
Seasonality and Children’s Blood Lead Levels: Developing a Predictive Model Using Climatic Variables and Blood Lead Data from Indianapolis, Indiana, Syracuse, New York, and New Orleans, Louisiana (USA)
Authors: Mark A.S. Laidlaw, Howard W. Mielke, Gabriel M. Filippelli, David L. Johnson, Christopher R. Gonzales
Journal: Environmental Health Perspectives (2005)

On a community basis, urban soil contains a potentially large reservoir of accumulated lead. This study was undertaken to explore the temporal relationship between pediatric blood lead (BPb), weather, soil moisture, and dust in Indianapolis, Indiana; Syracuse, New York; and New Orleans, Louisiana. The Indianapolis, Syracuse, and New Orleans pediatric BPb data were obtained from databases of 15,969, 14,467, and 2,295 screenings, respectively, collected between December 1999 and November 2002, January 1994 and March 1998, and January 1998 and May 2003, respectively. These average monthly child BPb levels were regressed against several independent variables: average monthly soil moisture, particulate matter < 10 μm in diameter (PM10), wind speed, and temperature. Of temporal variation in urban children's BPb, 87% in Indianapolis (R2 = 0.87, p = 0.0004), 61% in Syracuse (R2 = 0.61, p = 0.0012), and 59% in New Orleans (R2 = 0.59, p = 0.0000078) are explained by these variables. A conceptual model of urban Pb poisoning is suggested: When temperature is high and evapotranspiration maximized, soil moisture decreases and soil dust is deposited. Under these combined weather conditions, Pb-enriched PM10 dust disperses in the urban environment and causes elevated Pb dust loading. Thus, seasonal variation of children's Pb exposure is probably caused by inhalation and ingestion of Pb brought about by the effect of weather on soils and the resulting fluctuation in Pb loading.
Increased Occipital Cortex GABA Concentrations in Depressed Patients After Therapy With Selective Serotonin Reuptake Inhibitors
Authors: Gerard Sanacora, Graeme F Mason, Douglas L Rothman, John H Krystal
Journal: American Journal of Psychiatry (2002)

OBJECTIVE: Studies have demonstrated low concentrations of γ-aminobutyric acid (GABA) in the plasma and CSF of individuals with major depression, and low GABA concentrations have also been found in the occipital cortex of depressed subjects. The goal of this study was to determine whether these occipital cortex GABA concentrations are altered after administration of selective serotonin reuptake inhibitors (SSRIs) in the treatment of depression. METHOD: By means of proton magnetic resonance spectroscopy, occipital cortex GABA concentrations were measured in 11 medication-free depressed patients before initiation of treatment with SSRI medications and after an average of 2 months of treatment. RESULTS: A significant increase in occipital cortex GABA concentrations was seen after SSRI treatment. CONCLUSIONS: SSRI treatment of major depression is associated with increased occipital cortex GABA concentrations. This appears to result in a normalization of low pretreatment GABA concentrations, an effect that may contribute to a common mechanism of antidepressant action.
Defective B cell tolerance in adenosine deaminase deficiency is corrected by gene therapy
Authors: Aisha V. Sauer, Henner Morbach, Immacolata Brigida, Yen-Shing Ng, Alessandro Aiuti, Eric Meffre
Journal: Journal of Clinical Investigation (2012)

Adenosine deaminase (ADA) gene defects are among the most common causes of SCID. Restoration of purine metabolism and immune functions can be achieved by enzyme replacement therapy, or more effectively by bone marrow transplant or HSC gene therapy (HSC-GT). However, autoimmune complications and autoantibody production, including anti-nuclear antibodies (ANAs), frequently occur in ADA-SCID patients after treatment. To assess whether ADA deficiency affects the establishment of B cell tolerance, we tested the reactivity of recombinant antibodies isolated from single B cells of ADA-SCID patients before and after HSC-GT. We found that before HSC-GT, new emigrant/transitional and mature naive B cells from ADA-SCID patients contained more autoreactive and ANA-expressing clones, indicative of defective central and peripheral B cell tolerance checkpoints. We further observed impaired B cell receptor (BCR) and TLR functions in B cells after ADA inhibition, which may underlie the defects in B cell tolerance. Strikingly, after HSC-GT, ADA-SCID patients displayed quasi-normal early B cell tolerance checkpoints, as evidenced by restored removal of developing autoreactive and ANA-expressing B cells. Hence, ADA plays an essential role in controlling autoreactive B cell counterselection by regulating BCR and TLR functions.
Indolo[3, 2-b]carbazole: a Dietary-Derived Factor That Exhibits Both Antiestrogenic and Estrogenic Activity
Authors: H. Liu, M. Wormke, S. H. Safe
Journal: JNCI Journal of the National Cancer Institute (1994)

Journal Article Indolo[3, 2-b]carbazole: a Dietary-Derived Factor That Exhibits Both Antiestrogenic and Estrogenic Activity Get access Hong Liu, Hong Liu Department of Veterinary Physiology and Pharmacology, Texas A&M University, College Station.L. F. Bjeldanes, Department of Nutritional Sciences, University of CaliforniaBerkeley, Calif Search for other works by this author on: Oxford Academic PubMed Google Scholar Mark Wormke, Mark Wormke Department of Veterinary Physiology and Pharmacology, Texas A&M University, College Station.L. F. Bjeldanes, Department of Nutritional Sciences, University of CaliforniaBerkeley, Calif Search for other works by this author on: Oxford Academic PubMed Google Scholar Stephen H. Safe Stephen H. Safe Department of Veterinary Physiology and Pharmacology, Texas A&M University, College Station.L. F. Bjeldanes, Department of Nutritional Sciences, University of CaliforniaBerkeley, Calif Correspondence to : Stephen H. Safe, Ph.D., Department of Veterinary Physiology and Pharmacology, Texas A&M University. College Station. TX 77843-4466. Search for other works by this author on: Oxford Academic PubMed Google Scholar JNCI: Journal of the National Cancer Institute, Volume 86, Issue 23, 7 December 1994, Pages 1758–1765, https://doi.org/10.1093/jnci/86.23.1758 Published: 07 December 1994 Article history Received: 04 May 1994 Revision received: 01 September 1994 Accepted: 01 September 1994 Published: 07 December 1994
Comparison of Long-term Prognosis of Patients With AIDS Treated and Not Treated With Zidovudine
Authors: Jens D. Lundgren
Journal: JAMA (1994)

<h3>Objective.</h3> —To determine the association between elapsed time since starting zidovudine and survival in patients with acquired immunodeficiency syndrome (AIDS). <h3>Design.</h3> —Inception cohort and observational study of patients treated and not treated with zidovudine. <h3>Setting.</h3> —Fifty-one centers in 17 European countries. <h3>Patients.</h3> —A total of 4484 patients diagnosed as having AIDS from 1979 to 1989 who survived their initial AIDS-defining event and who had not started zidovudine before AIDS diagnosis. <h3>Main Outcome Measures.</h3> —Use of zidovudine and mortality. <h3>Results.</h3> —Among patients who did not receive zidovudine, the death rate was approximately constant for the first 5 years after AIDS diagnosis. For patients treated with zidovudine, the death rate within the first year since starting zidovudine was markedly lower than for untreated patients who had developed AIDS at the same time (relative rate, 0.47; 95% confidence interval [CI] 0.42 to 0.51). For longer times since starting zidovudine, the association with reduced mortality rate was diminished, and for patients surviving more than 2 years since starting zidovudine, the death rate was greater than for untreated patients who had developed AIDS at the same time (relative rate, 1.35; 95% CI, 1.15 to 1.58). Adjustment for other prognostic factors failed to substantially affect this observation. <h3>Conclusions.</h3> —When initiated after the time of AIDS diagnosis, zidovudine was associated with improved prognosis but for no more than 2 years after starting therapy. (<i>JAMA</i>. 1994;271:1088-1092)
Phase II study of temozolomide in heavily pretreated cancer patients with brain metastases
Authors: C. Christodoulou, D. Bafaloukos, P. Kosmidis, E. Samantas, A. Bamias, P. Papakostas, A. Karabelis, C. Bacoyiannis, D.V. Skarlos
Journal: Annals of Oncology (2001)
Effects of Exenatide (Exendin-4) on Glycemic Control Over 30 Weeks in Patients With Type 2 Diabetes Treated With Metformin and a Sulfonylurea
Authors: David M. Kendall, Matthew C. Riddle, Julio Rosenstock, Dongliang Zhuang, Dennis D. Kim, Mark S. Fineman, Alain D. Baron
Journal: Diabetes Care (2005)

OBJECTIVE—This study evaluated the effects of exenatide, a novel incretin mimetic, in hyperglycemic patients with type 2 diabetes unable to achieve glycemic control with metformin-sulfonylurea combination therapy. RESEARCH DESIGN AND METHODS—A 30-week, double-blind, placebo-controlled study was performed in 733 subjects (aged 55 ± 10 years, BMI 33.6 ± 5.7 kg/m2, A1C 8.5 ± 1.0%; means ± SD) randomized to 5 μg subcutaneous exenatide b.i.d. (arms A and B) or placebo for 4 weeks. Thereafter, arm A remained at 5 μg b.i.d. and arm B escalated to 10 μg b.i.d. Subjects continued taking their dose of metformin and were randomized to either maximally effective (MAX) or minimum recommended (MIN) doses of sulfonylurea. RESULTS—Week 30 A1C changes from baseline (±SE) were −0.8 ± 0.1% (10 μg), −0.6 ± 0.1% (5 μg), and +0.2 ± 0.1% (placebo; adjusted P &amp;lt; 0.0001 vs. placebo), yielding placebo-adjusted reductions of −1.0% (10 μg) and −0.8% (5 μg). In the evaluable population, exenatide-treated subjects were more likely to achieve A1C ≤7% than placebo-treated subjects (34% [10 μg], 27% [5 μg], and 9% [placebo]; P &amp;lt; 0.0001). Both exenatide arms demonstrated significant weight loss (−1.6 ± 0.2 kg from baseline each exenatide arm, −0.9 ± 0.2 kg placebo; P ≤ 0.01 vs. placebo). Mild or moderate nausea was the most frequent adverse event. The incidence of mild/moderate hypoglycemia was 28% (10 μg), 19% (5 μg), and 13% (placebo) and appeared lower with MIN than with MAX sulfonylurea treatment. CONCLUSIONS—Exenatide significantly reduced A1C in patients with type 2 diabetes unable to achieve adequate glycemic control with maximally effective doses of combined metformin-sulfonylurea therapy. This improvement in glycemic control was associated with no weight gain and was generally well tolerated.
NVP-LAQ824 is a potent novel histone deacetylase inhibitor with significant activity against multiple myeloma
Authors: Laurence Catley, Ellen Weisberg, Yu-Tzu Tai, Peter Atadja, Stacy Remiszewski, Teru Hideshima, Nicholas Mitsiades, Reshma Shringarpure, Richard LeBlanc, Dharminder Chauhan, Nikhil C. Munshi, Robert Schlossman, Paul Richardson, James Griffin, Kenneth C. Anderson
Journal: Blood (2003)
An electronic nose can distinguish between different asthma phenotypes
Authors: Timm Greulich, Peter J. Sterk, David Hamm, Janine Koepke, Akira Hattesohl, Christoph Nell, Claus F. Vogelmeier, Carola Seifart, Andreas R. Koczulla
Journal: European Respiratory Journal (2013)

Rationale: As current research in asthma reveals an increasing number of clinically relevant phenotypes, targeted therapy becomes increasingly important. The diagnosis of eosinophilic asthma via sputum induction is technically demanding, cost-intensive and time-consuming. Electronic noses can assess distinct molecular patterns of volatile organic compounds by in exhaled breath of different patient groups. We determined the diagnostic accuracy of an electronic nose in the distinction between patients with eosinophilic asthma, non-eosinophilic asthma and non-asthmatic controls.

Study Participants/Methods: We included 40 adult, steroid-naive participants (9 eosinophilic asthma, 11 non-eosinophilic asthma, 10 allergic rhinitis, 10 healthy controls) in this study. Sputum induction, spirometry, measurement of fraction of exhaled nitric oxide (FeNO), and exhaled breath analysis via the Cyranose 320™ was done. For statistical analysis the linear discriminant analysis was performed.

Results: We identified a Linear Discriminant function separating the eNose derived volatile organic compound pattern from eosinophilic vs. non-eosinophilic asthma (p<0.0001). The corresponding area under the Receiver Operating Curve (AUC, 95%CI, p-value) to predict sputum eosinophilia was 1.0 (0.96 – 1.0; p<0.0001; cross validation value 59.1%) and superior to the ability of blood eosinophils (0.93, 0.81 – 1.0; p=0.0013) and FeNO (0.82, 0.58 – 1.1, p=0.0208).

Conclusion: An electronic nose may be able to distinguish exhaled breath from eosinophilic and non-eosinophilic asthma patients who are steroid-naive. In general, our results provide the opportunity to guide steroid treatment by non-invasive, real time breath analysis.
A study on the epidemiology of rosacea in the U.K.
Authors: J. Spoendlin, J.J. Voegel, S.S. Jick, C.R. Meier
Journal: British Journal of Dermatology (2012)

Background Rosacea is a chronic facial skin disease of unclear origin. Epidemiological data are scarce and controversial, with reported prevalences ranging from 0·09% to 22%. To our knowledge, incidence rates have not been quantified before. Objectives In this observational study we quantified incidence rates of diagnosed rosacea in the U.K. and described demographic characteristics and the prevalence of ocular symptoms in patients with rosacea. We compared lifestyle factors such as smoking and alcohol consumption between patients with rosacea and controls. Methods Using the U.K.-based General Practice Research Database, we identified patients with an incident diagnosis of rosacea between 1995 and 2009 and matched them (1 : 1) to rosacea-free control patients. We assessed person-time of all patients at risk and assessed incidence rates of rosacea, stratified by age, sex, year of diagnosis and region. Results We identified 60 042 rosacea cases and 60 042 controls (61·5% women). The overall incidence rate for diagnosed rosacea in the U.K. was 1·65 per 1000 person-years. Rosacea was diagnosed in some 80% of cases after the age of 30 years. Ocular symptoms were recorded in 20·8% of cases at the index date. We observed a significantly reduced relative risk of developing rosacea among current smokers (odds ratio 0·64, 95% confidence interval 0·62–0·67). Alcohol consumption was associated with a marginal risk increase. Conclusions We quantified incidence rates and characteristics of patients with rosacea diagnosed in clinical practice in a large epidemiological study using primary care data from the U.K. Smoking was associated with a substantially reduced risk of developing rosacea.
Retrospective Analysis of Induction Chemotherapy with Docetaxel, CDDP and S-1 Followed by CRT for Nasopharyngeal Cancer
Authors: T. Yamazaki, H. Ishiki, T. Enokida, S. Fujii, S. Zenda, S. Arahira, M. Kawashima, T. Akimoto, M. Tahara
Journal: Annals of Oncology (2013)
TR-02 * INHIBITION OF AKT SIGNALING AND TUMOR GROWTH BY SUPERCRITICAL CO2 EXTRACT OF MANGO GINGER (CURCUMA AMADA ROXB.) IN HUMAN GLIOBLASTOMA CELL LINE IN VITRO AND IN NUDE MICE XENOGRAFTS
Authors: C. Ramachandran, G. Portalatin, K.-W. Quirin, E. Escalon, Z. Khatib, S. Melnick
Journal: Neuro-Oncology (2015)

Mango ginger (Curcuma amada Roxb.), a tropical medicinal plant and spice from Asia, has not been well-investigated for its anticancer properties unlike turmeric (Curcuma longa L.) or the active ingredient curcumin. The inhibitory effect of supercritical CO2 extract of mango ginger (CA) on AKT signaling was investigated in U-87MG glioblastoma cells. CA was highly cytotoxic to glioblastoma cell line (IC50 = 4.92 ± 0.81 µg/ml) compared to mHypoE-N1 normal mouse hypothalamus cell line (IC50 = 40.57 ± 0.06 µg/ml). When CA was combined with irinotecan (IR), temozolomide or vincristine, CA showed synergistic cytotoxicity with combination index values of <1 in glioblastoma cells. CA inhibits AKT and AMPKα phosphorylation significantly in a dose-dependent manner. The cell migration, which is necessary for invasion and metastasis, was also inhibited by CA treatment with about 43% inhibition at 20 µg/ml concentration. Analysis of mRNA and protein expression of genes showed that CA modulates expression of genes associated with apoptosis (Bax, Bcl-2, Bcl-X, BNIP3, caspase-3, mutant p53, and p21), cell proliferation (Ki67) and angiogenesis (VEGF). Additionally, HSP90 and AMPKα which interact with the AKT signaling pathway were down regulated by CA treatment. Analysis of tumor growth inhibition in nude mice xenografts transplanted with U-87MG glioblastoma cells showed that CA treatment has reduced tumor growth rate by 40.2%, IR by 23.7% and CA + IR by 99.5%. Both CA and CA + IR treated xenografts showed better survival rate than IR and control (saline) groups (*p < 0.0328). These results indicated the molecular targets underlying the anticancer effect of CA in human glioblastoma cells and the potential use of CA as an adjuvant for therapeutic management of glioblastoma.
Human Immunodeficiency Virus Transmission at Each Step of the Care Continuum in the United States
Authors: Jacek Skarbinski, Eli Rosenberg, Gabriela Paz-Bailey, H. Irene Hall, Charles E. Rose, Abigail H. Viall, Jennifer L. Fagan, Amy Lansky, Jonathan H. Mermin
Journal: JAMA Internal Medicine (2015)

Human immunodeficiency virus (HIV) transmission risk is primarily dependent on behavior (sexual and injection drug use) and HIV viral load. National goals emphasize maximizing coverage along the HIV care continuum, but the effect on HIV prevention is unknown.To estimate the rate and number of HIV transmissions attributable to persons at each of the following 5 HIV care continuum steps: HIV infected but undiagnosed, HIV diagnosed but not retained in medical care, retained in care but not prescribed antiretroviral therapy, prescribed antiretroviral therapy but not virally suppressed, and virally suppressed.A multistep, static, deterministic model that combined population denominator data from the National HIV Surveillance System with detailed clinical and behavioral data from the National HIV Behavioral Surveillance System and the Medical Monitoring Project to estimate the rate and number of transmissions along the care continuum. This analysis was conducted January 2013 to June 2014. The findings reflect the HIV-infected population in the United States in 2009.Estimated rate and number of HIV transmissions.Of the estimated 1,148,200 persons living with HIV in 2009, there were 207,600 (18.1%) who were undiagnosed, 519,414 (45.2%) were aware of their infection but not retained in care, 47,453 (4.1%) were retained in care but not prescribed ART, 82,809 (7.2%) were prescribed ART but not virally suppressed, and 290,924 (25.3%) were virally suppressed. Persons who are HIV infected but undiagnosed (18.1% of the total HIV-infected population) and persons who are HIV diagnosed but not retained in medical care (45.2% of the population) were responsible for 91.5% (30.2% and 61.3%, respectively) of the estimated 45,000 HIV transmissions in 2009. Compared with persons who are HIV infected but undiagnosed (6.6 transmissions per 100 person-years), persons who were HIV diagnosed and not retained in medical care were 19.0% (5.3 transmissions per 100 person-years) less likely to transmit HIV, and persons who were virally suppressed were 94.0% (0.4 transmissions per 100 person-years) less likely to transmit HIV. Men, those who acquired HIV via male-to-male sexual contact, and persons 35 to 44 years old were responsible for the most HIV transmissions by sex, HIV acquisition risk category, and age group, respectively.Sequential steps along the HIV care continuum were associated with reduced HIV transmission rates. Improvements in HIV diagnosis and retention in care, as well as reductions in sexual and drug use risk behavior, primarily for persons undiagnosed and not receiving antiretroviral therapy, would have a substantial effect on HIV transmission in the United States.
The Mood Spectrum in Unipolar and Bipolar Disorder: Arguments for a Unitary Approach
Authors: Giovanni B Cassano, Paola Rucci, Ellen Frank, Andrea Fagiolini, Liliana Dell'Osso, M Katherine Shear, David J Kupfer
Journal: American Journal of Psychiatry (2004)

OBJECTIVE: This study examined the extent to which individuals with a lifetime diagnosis of recurrent unipolar disorder endorse experiencing manic/hypomanic symptoms over their lifetimes and compared their reports with those of patients with bipolar I disorder. METHOD: The study group included 117 patients with remitted recurrent unipolar depression and 106 with bipolar I. Subjects had their clinical diagnosis confirmed by the Mini International Neuropsychiatric Interview and were administered the Structured Clinical Interview for the Mood Spectrum, which assesses lifetime symptoms, traits, and lifestyles that characterize threshold and subthreshold mood episodes as well as "temperamental" features related to mood dysregulation. RESULTS: The patients with recurrent unipolar depression endorsed experiencing a substantial number of manic/hypomanic symptoms over their lifetimes. In both patients with recurrent unipolar depression and patients with bipolar I disorder, the number of manic/hypomanic items endorsed was related to the number of depressive items endorsed. In the group with recurrent unipolar depression, the number of manic/hypomanic items was related to an increased likelihood of endorsing paranoid and delusional thoughts and suicidal ideation. In the bipolar I group, the number of lifetime manic/hypomanic items was related to suicidal ideation and just one indicator of psychosis. CONCLUSIONS: The presence of a significant number of manic/hypomanic items in patients with recurrent unipolar depression seems to challenge the traditional unipolar-bipolar dichotomy and bridge the gap between these two categories of mood disorders. The authors argue that their mood spectrum approach is useful in making a more accurate diagnostic evaluation in patients with mood disorders.
Molecular Insights on the Peripheral and Intratumoral Effects of Systemic High-Dose rIL-2 (Aldesleukin) Administration for the Treatment of Metastatic Melanoma
Authors: Geoffrey R. Weiss, William W. Grosh, Kimberly A. Chianese-Bullock, Yingdong Zhao, Hui Liu, Craig L. Slingluff, Francesco M. Marincola, Ena Wang
Journal: Clinical Cancer Research (2011)

We have previously shown that within tumors, recombinant interleukin-2 (rIL-2, aldesleukin) consistently activates tumor-associated macrophages and upregulates IFN-stimulated genes while inducing minimal migration, activation, or proliferation of T cells. These effects are independent of tumor response to treatment. Here, we prospectively evaluated transcriptional alterations induced by rIL-2 in peripheral blood mononuclear cells (PBMC) and within melanoma metastases.We evaluated gene expression changes by serially comparing pre- to posttreatment samples in 13 patients and also compared transcriptional differences among lesions displaying different responsiveness to therapy, focusing on 2 lesions decreasing in size and 2 remaining stable (responding lesions) compared with nonresponding ones.As previously described, the effects of rIL-2 were dramatic within PBMCs, whereas effects within the tumor microenvironment were lesion specific and limited. However, distinct signatures specific to response could be observed in responding lesions pretreatment that were amplified following rIL-2 administration. These signatures match the functional profile observed in other human or experimental models in which immune-mediated tissue-specific destruction (TSD) occurs, underscoring common pathways leading to rejection. Moreover, the signatures observed in pretreatment lesions were qualitatively similar to those associated with TSD, underlining a determinism to immune responsiveness that depends upon the genetic background of the host or the intrinsic genetic makeup of individual tumors.This is the first prospectively collected insight on global transcriptional events occurring during high-dose rIL-2 therapy in melanoma metastases responding to treatment.