tbuckley/cabot-search huggingface dataset:
Methamphetamine and young men who have sex with men.
Authors: Robert Garofalo, Brian S Mustanski, David J McKirnan, Amy Herrick, Geri R Donenberg
Journal: JAMA Pediatrics (2007)

The objective was to examine patterns consequences and correlates of methamphetamine use among adolescent and young adult men who have sex with men (YMSM). Design: Descriptive bivariate and hierarchical regression analyses of cross-sectional data. Setting: Howard Brown Health Center a community-based facility in Chicago Ill from August 2004 to September 2005. Participants: Three hundred ten YMSM who completed an anonymous computer-assisted survey. Main Outcome Measure: Methamphetamine use in the past year. Participants ranged in age from 16 to 24 years (mean age 20.3 years); 30% were white and 70% were of other race/ethnicity (African American 33%; Hispanic 26%; Asian or Pacific Islander 3%; and other 8%). Participants reported many high-risk sexual and substance use behaviors. Thirteen percent used methamphetamine in the past year. Methamphetamine use was more common among human immunodeficiency virus-infected participants (odds ratio 2.8; 95% confidence interval 1.3-5.3) and varied by age and race/ethnicity; substantially higher prevalence was reported by older and non-African American YMSM (P less than .001). Compared with other illicit substance users methamphetamine users reported more memory difficulties impairments in daily activities and unintended risky sex resulting from substance use (all P less than .01). Hierarchical regression identified sexual risk (unprotected intercourse and multiple partners) sexualized social context (eg Internet sex sex in a bathhouse or sex club sex with older partners and commercial sex) lower self-esteem and psychological distress as correlated with methamphetamine use among participants (P less than .05). A substantial percentage of YMSM in this sample used methamphetamine. Methamphetamine use is a public health problem with significant implications for the health and well-being of YMSM. Methamphetamine use was associated with human immunodeficiency virus-related risk and patterns of use were predicted by demographic data sexualized social contexts and psychological variables. (authors)
Randomized comparison of weekly or every-3-week (q3w) nab-paclitaxel compared to q3w docetaxel as first-line therapy in patients (pts) with metastatic breast cancer (MBC)
Authors: W. Gradishar, D. Krasnojon, S. Cheporov, A. Makhson, G. Manikhas, A. Clawson, M. J. Hawkins
Journal: Journal of Clinical Oncology (2007)

1032 Background: 130-nM albumin-bound (nab™) paclitaxel combines paclitaxel with albumin without solvents or altering either component. A cross analysis of 2 clinical trials comparing solvent-based (SB) paclitaxel 175 mg/m 2 q3w to nab- paclitaxel (Gradishar et al, JCO, 2005) and SB docetaxel (Jones et al, JCO, 2005) suggested comparable antitumor activity between nab-paclitaxel and SB docetaxel and better tolerability with nab-paclitaxel in pts with MBC. The aim of this study was to compare the toxicity and antitumor activity of 3 regimens of nab-paclitaxel (q3w and 2 weekly) with each other and that of SB docetaxel in MBC. Methods: In this open-label study, first-line pts with MBC were randomly assigned to nab-paclitaxel 300 mg/m 2 q3w (A); nab-paclitaxel 100 mg/m 2 (B) or 150 mg/m 2 (C) days 1, 8, and 15, q28 days (q 3/4 w); or SB docetaxel 100 mg/m 2 q3w (D). The primary endpoints were overall response rate (complete response + partial response, evaluated q8w) and toxicity. Progression-free survival (PFS) was also determined. Results: 302 pts (median age, 54 years; 99% Caucasian; 75% postmenopausal; ECOG PS =2 [94% =1]) either had at least 2 response assessments (94%) or had discontinued due to PD (6%). The efficacy results are shown in the Table . Neutropenia (N) was greater with D than with A, B, or C (p &lt; 0.001). Grade 4 N was: A) 4%, B) 3%, C) 7%, and D) 74%. Febrile neutropenia (FN) was: A) 1%, B) 1%, C) 1%, and D) 7%. Gr 3 peripheral neuropathy was: A) 14%, B) 7%, C) 12%, and D) 5%. Conclusions: The response rates of q3w nab-paclitaxel and solvent-based docetaxel were comparable. Q 3/4 W nab-paclitaxel resulted in higher response rates than solvent-based docetaxel. Grade 4 N and FN were less frequent with nab-paclitaxel as compared with solvent-based docetaxel. To date, all 3 nab-paclitaxel regimens have a longer PFS than SB docetaxel although the data are not yet mature (33% of events). Final data for a radiological review of response data, PFS, and toxicity will be presented. [Table: see text] No significant financial relationships to disclose.
Myeloid differentiation protein 2 facilitates pollen- and cat dander–induced innate and allergic airway inflammation
Authors: Koa Hosoki, Istvan Boldogh, Leopoldo Aguilera-Aguirre, Qian Sun, Toshiko Itazawa, Tapas Hazra, Allan R. Brasier, Alexander Kurosky, Sanjiv Sur
Journal: Journal of Allergy and Clinical Immunology (2015)
Abstract P6-13-08: The DCIS Score - Potential for healthcare savings?
Authors: Rebekah Young, Kimberly Gergelis, Shalom Kalnicki, Jana L Fox
Journal: Cancer Research (2015)

Abstract Introduction The Oncotype Dx Recurrence Score for DCIS (DCIS Score) is a 12-gene assay derived from the original Oncotype DX test that evaluates recurrence risk among women with invasive carcinoma of the breast. The DCIS Score provides a local recurrence risk estimate at 10 years following lumpectomy for ductal carcinoma in situ (DCIS). Results can help guide decisions regarding adjuvant radiation (RT). Foregoing RT can be a source of significant healthcare savings. We investigated the actual healthcare dollar savings to-date in our patient population. Methods We evaluated patients in whom the DCIS Score was ordered (x) and calculated total cost of testing. Potential cost of RT was that of IMRT as reimbursed by Medicare for a hypofractionated (16 fraction) course, multiplied by x. Many of our large-breasted patients require IMRT to increase dose homogeneity and to limit dose to normal tissues. We also calculated potential cost with 3D conformal (3D-CRT). Total potential cost was the sum of testing and treatment costs, determined for each modality. The number of patients ultimately treated (y) was also multiplied by these costs. Total actual cost was the sum of test expenses and actual treatment costs. Savings was the difference between the total actual and total potential cost. Results From February, 2012 to May, 2014 the DCIS Score was performed in 38 patients (x= 38). Median age was 66 (40-85). Grade was low in 39%, intermediate in 45%, and high in 16%. 50% had necrosis present, and the median size of DCIS was 0.5cm (0.1 - 3.1cm). The total cost of testing was $4125 * 38 = $156,750. IMRT reimburses at approximately $23, 000 and 3D-CRT at approximately $11,000 per treatment. (Medicare reimbursement rates can vary among states.) The potential total cost of RT ranged from $418,000 - $874, 000; testing brought the total potential costs to $574, 750 - $1,030, 750. Upon receipt of the test results, 12 (y) patients ultimately underwent therapy. IMRT was given in 11 patients and 3D-CRT in 1, for a total treatment cost of $264, 000. Therefore, total actual expenditures were $420, 750. Savings amounted to (574, 750 – 420, 750) = $154, 000 to (1,030, 750– 420, 750) = $ 610, 000. Conclusions In the era of rising healthcare costs, it is imperative to examine instances of possible over-treatment. The DCIS Score has the potential to save not only healthcare dollars, but to spare patients radiation side effects, time lost from work, and transportation expenses. While there are costs associated with the assay, if ordered judiciously, these can be offset by the subsequent savings from eliminating treatment. Citation Format: Rebekah Young, Kimberly Gergelis, Shalom Kalnicki, Jana L Fox. The DCIS Score - Potential for healthcare savings? [abstract]. In: Proceedings of the Thirty-Seventh Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2014 Dec 9-13; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2015;75(9 Suppl):Abstract nr P6-13-08.
Receptor editing and genetic variability in human autoreactive B cells
Authors: Julie Lang, Takayuki Ota, Margot Kelly, Pamela Strauch, Brian M. Freed, Raul M. Torres, David Nemazee, Roberta Pelanda
Journal: The Journal of Experimental Medicine (2015)

The mechanisms by which B cells undergo tolerance, such as receptor editing, clonal deletion, and anergy, have been established in mice. However, corroborating these mechanisms in humans remains challenging. To study how autoreactive human B cells undergo tolerance, we developed a novel humanized mouse model. Mice expressing an anti–human Igκ membrane protein to serve as a ubiquitous neo self-antigen (Ag) were transplanted with a human immune system. By following the fate of self-reactive human κ+ B cells relative to nonautoreactive λ+ cells, we show that tolerance of human B cells occurs at the first site of self-Ag encounter, the bone marrow, via a combination of receptor editing and clonal deletion. Moreover, the amount of available self-Ag and the genetics of the cord blood donor dictate the levels of central tolerance and autoreactive B cells in the periphery. Thus, this model can be useful for studying specific mechanisms of human B cell tolerance and to reveal differences in the extent of this process among human populations.
Use of Coronary Artery Calcium Scanning to Screen for Coronary Atherosclerosis Among Early Middle-Age Adults⁎⁎Editorials published in JACC: Cardiovascular Imaging reflect the views of the authors and do not necessarily represent the views of JACC: Cardiovascular Imaging or the American College of Cardiology.
Authors: Alan Rozanski, Daniel S. Berman
Journal: JACC. Cardiovascular imaging (2012)
Omentin attenuates atherosclerotic lesion formation in apolipoprotein E-deficient mice
Authors: Mizuho Hiramatsu-Ito, Rei Shibata, Koji Ohashi, Yusuke Uemura, Noriyoshi Kanemura, Takahiro Kambara, Takashi Enomoto, Daisuke Yuasa, Kazuhiro Matsuo, Masanori Ito, Satoko Hayakawa, Hayato Ogawa, Naoya Otaka, Shinji Kihara, Toyoaki Murohara, Noriyuki Ouchi
Journal: Cardiovascular Research (2015)

Obesity is associated with the development of atherosclerosis. We previously demonstrated that omentin is a circulating adipokine that is downregulated in association with atherosclerotic diseases. Here, we examined the impact of omentin on the development of atherosclerosis with gain-of-function genetic manipulations and dissected its potential mechanism. Apolipoprotein E-deficient (apoE-KO) mice were crossed with transgenic mice expressing the human omentin gene (OMT-Tg) mice in fat tissue to generate apoE-KO/OMT-Tg mice. ApoE-KO/OMT-Tg mice exhibited a significant reduction of the atherosclerotic areas in aortic sinus, compared with apoE-KO mice despite similar lipid levels. ApoE-KO/OMT-Tg mice also displayed significant decreases in macrophage accumulation and mRNA expression of proinflammatory mediators including tumour necrosis factor-α, interleukin-6, and monocyte chemotactic protein-1 in aorta when compared with apoE-KO mice. Treatment of human monocyte-derived macrophages with a physiological concentration of human omentin protein led to reduction of lipid droplets and cholesteryl ester content. Treatment with human omentin protein also reduced lipopolysaccharide-induced expression of proinflammatory genes in human macrophages. Treatment of human macrophages with omentin promoted the phosphorylation of Akt. Inhibition of Akt signalling abolished the anti-inflammatory actions of omentin in macrophages. These data document for the first time that omentin reduces the development of atherosclerosis by reducing inflammatory response of macrophages through the Akt-dependent mechanisms.
Oncostatin M induces VEGF through regulation of HIF-1α
Authors: David Chang, Sujatha Kadaba, Bengt Phung, Alexander Ide, Cheryl Jorcyk
Journal: Cancer Research (2008)

2044  Oncostatin M (OSM), a gp130-multifunctional cytokine, has been shown to inhibit the proliferation of breast and other tumor cell line, and attention has been given to OSM as a potential cancer therapeutic. However, more recent studies have shown that OSM stimulates cell detachment and invasion and induces vascular endothelial growth factor (VEGF) in endothelial and astroglioma cells suggesting that OSM may play a role in angiogenesis and tumor progression. We demonstrate a novel property of OSM in the upregulation of hypoxia-inducible factor-1α (HIF-1α), a potent pro-angiogenic transcription factor necessary for the induction of VEGF. We subjected MDA-MB-231 and T47D human breast cancer cells to hypoxia or normoxia along with small molecule inhibitors to determine the mechanism of OSM-upregulated HIF-1α. We show that OSM inducement of HIF-1α is primarily through protein synthesis. In addition, we find that the expression of OSM-induced VEGF and HIF-1α is dependent on STAT3 involvement. Finally, unlike some gp130-cytokines, OSM appears to activate multiple signaling pathways necessary for the induction of VEGF. These results suggest the importance of designing therapeutics to inhibit OSM during breast cancer progression and subsequent metastasis.
Influence of Sex on Long-Term Outcomes After Implantation of Bare-Metal Stent
Authors: Kyohei Yamaji, Hiroki Shiomi, Takeshi Morimoto, Toshiaki Toyota, Koh Ono, Yutaka Furukawa, Yoshihisa Nakagawa, Kazushige Kadota, Kenji Ando, Shinichi Shirai, Masayuki Kato, Yoshiki Takatsu, Osamu Doi, Hirofumi Kambara, Satoru Suwa, Tomoya Onodera, Hirotoshi Watanabe, Masahiro Natsuaki, Takeshi Kimura
Journal: Circulation (2015)

Background— Female sex was reported to be associated with lower risk for midterm restenosis and repeat revascularization after bare-metal stent implantation. However, the influence of sex on very long-term outcomes after bare-metal stent implantation has not been yet reported. Methods and Results— Among the 9877 patients in the multicenter Coronary Revascularization Demonstrating Outcome study in Kyoto (CREDO-Kyoto) registry cohort-1, bare-metal stent implantation was performed in 5313 patients (men, n=3742 and women, n=1571). Follow-up was completed in 4515 patients (85.0%) at 10 years (duration, 10.3±3.1 [0.0–14.1] years). The cumulative incidence of target-lesion revascularization (TLR) was 27% at 1 year and 34% at 10 years (0.8%/y beyond 1 year). Non–target-lesion revascularization (non-TLR) was the dominant coronary revascularization beyond 1 year (13% at 1 year and 31% at 10 years [2.0%/y beyond 1 year]). Cumulative incidence of stent thrombosis was low (1.2% at 1 year and 1.9% at 10 years). Women were older and had greater prevalence of cardiovascular risk factors than men. The cumulative 10-year incidences of and adjusted risk for TLR were significantly higher in men than in women (36% versus 30%, P &lt;0.001; adjusted hazard ratio, 1.29; 95% confidence interval, 1.15–1.46; P &lt;0.001). The higher risk of men relative to women for TLR was consistent regardless of age (&lt;75 years and ≥75 years). Men in comparison with women were also associated with significantly higher adjusted risks for all-cause death, myocardial infarction, stroke, coronary artery bypass grafting, TLR, and non-TLR. Conclusions— TLR and stent thrombosis continued to occur without attenuation up to 10 years after bare-metal stent implantation. Men in comparison with women were associated with higher adjusted 10-year risks for all-cause death, myocardial infarction, stroke, coronary artery bypass grafting, TLR, and non-TLR.
Albumin serum levels and malnutrition are associated with toxicity secondary to paclitaxel-cisplatin chemotherapy in patients with advanced non-small cell lung cancer: A prospective study
Authors: K. Sanchez-Lara, C. Diaz-Romero, D. Motola-Kuba, C. Rodriguez, R. Sosa Sánchez, T. Ceron, D. Green, O. G. Arrieta
Journal: Journal of Clinical Oncology (2008)

9623 Background: Paclitaxel (P), is an hydrophobic molecule, the binding with plasma proteins like albumin could be an important determinant of its pharmacokinetic behavior; malnutrition and hypoalbuminemia are common in non-small cell lung cancer (NSCLC) patients, specially in non-developed countries. The aim of this study was to assess the effect of albumin serum levels and malnutrition with the presence of chemotherapy induced toxicity in this patients. Methods: We evaluated prospectively 70 stage IV NSCLC patients treated with chemotherapy based on P (175mg/m2) and cisplatin (80 mg/m2). Toxicity effects were graded according to the National Cancer Institute Criteria. Chi squared, Mann-Whitney´s U, multivariate analysis were made with logistical regression, and were used to associate clinical, biochemical parameters, and malnutrition. Malnutrition was assessed using the Subjective Global Assessment before starting treatment and after the 2nd chemotherapy cycle. Informed consent was obtained for all subjects and the study was approved by the hospital ethics committee. Results: Median age was 58± 9 years. 31% of all patients had malnutrition grade 1 and 11.5% grade 2. Grade III and IV toxicity was observed in 18% of patients. The main observed toxicities were alopecia (70%), neuropathy (42%), anemia (38%), loss weight (37%), and leucopenia (17%). More patients with grade 2 and 3 malnutrition had chemotherapy induced toxicity compared with patients without malnutrition (mean ranks 16 vs 10.6 p=0.05). Low albumin serum levels were also associated with toxicity, more patients with albumin levels ≤3.4 mg/mL had toxicity compared to patients with normal albumin (mean ranks 35.7 vs 20.9 p=0.02). The presence of Hipoalbuminemia was statistically associated with anemia (60 vs 27% p=0.032), nausea (70 vs 58% p=0.05) and loss of apetite (30 vs 10.9% p=0.003). Malnutrition compared with normal nutrition was associated to nausea (100% vs 53% p<0.05) and alopecy (88 vs 55% p<0.05). Conclusions: Malnutrition and hypoalbuminemia are associated with presence of chemotherapy induced toxicity in NSCLC patients treated with P and cisplatin. No significant financial relationships to disclose.
Novel statistical analysis of long-term survival to account for crossover in a phase III trial of sunitinib (SU) vs. placebo (PL) in advanced GIST after imatinib (IM) failure
Authors: G. D. Demetri, X. Huang, C. R. Garrett, P. Schöffski, M. E. Blackstein, M. H. Shah, J. Verweij, V. Tassell, C. M. Baum, P. G. Casali
Journal: Journal of Clinical Oncology (2008)

10524 Background: SU is an oral multitargeted tyrosine kinase inhibitor of KIT, PDGFRs, VEGFRs, FLT3, CSF-1R and RET, approved multinationally for treatment of advanced GIST after IM failure. Interim analysis of a double-blind, PL-controlled phase III trial in this pt population showed a significant difference in OS between pts randomized to SU (50 mg/d administered in 6-wk cycles of 4 wk on treatment, 2 wk off; N=207) or PL (N=105) favoring SU (HR 0.49; P=0.007), without medians having been reached. The study design allowed PL pts to cross over to SU at PD or unblinding of the trial. While efficacy and safety/tolerability continue to be assessed, conventional statistical methods yield biased treatment-effect estimates for mature OS data because of the crossover. Methods: In addition to the log-rank test, Cox model and Kaplan-Meier method, OS was analyzed using the rank-preserving structural failure time (RPSFT) method to account for crossover. Results: Across the entire study (double-blind + open-label phases), 243 pts were randomized to receive SU and 118 pts to receive PL, 104 of whom crossed over to SU. As of Nov. 2007, conventional analysis showed that OS converged in the two treatment groups (SU median 74.7 wk, 95% CI 61.4–85.7; PL 64.9 wk, 45.7–98.4; HR 0.82, P=0.128) as expected, given the crossover design. However, RPSFT analysis yielded an estimated median OS for PL of 36.0 wk (95% CI 25.9–51.0), revealing a significant SU treatment effect (HR 0.46, P<0.0001) comparable to that of the blinded phase. As in the blinded phase, the most common treatment-related AEs throughout the entire study were fatigue, diarrhea, nausea and skin discoloration, mainly grade 1/2; incidences increased slightly with extended SU treatment. The frequencies of hematologic laboratory abnormalities were similar for shorter-term and extended SU treatment. The incidence of cardiac AEs was low with SU across the study (4.3%). Conclusions: Use of RPSFT analysis to account for crossover confirmed the long-term OS benefit provided by SU vs. PL to pts with IM-resistant/intolerant GIST in this phase III study, with implications for other crossover trials. SU demonstrated acceptable, predictable safety with long-term treatment. Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Expert Testimony Other Remuneration Pfizer Inc. GlaxoSmithKline, Infinity, MedImmune, Novartis, Pfizer Inc., sanofi-aventis Pfizer Inc. Novartis, Pfizer Inc., PharmaMar, SigmaTau Infinity, Jansen Cilag, Novartis, Pfizer Inc., SigmaTau Infinity, Novartis, Pfizer Inc. Novartis, PharmaMar
Citrus Flavonoids as Regulators of Lipoprotein Metabolism and Atherosclerosis
Authors: Erin E. Mulvihill, Amy C. Burke, Murray W. Huff
Journal: Annual Review of Nutrition (2016)

Citrus flavonoids are polyphenolic compounds with significant biological properties. This review summarizes recent advances in understanding the ability of citrus flavonoids to modulate lipid metabolism, other metabolic parameters related to the metabolic syndrome, and atherosclerosis. Citrus flavonoids, including naringenin, hesperitin, nobiletin, and tangeretin, have emerged as potential therapeutics for the treatment of metabolic dysregulation. Epidemiological studies reveal an association between the intake of citrus flavonoid-containing foods and a decreased incidence of cardiovascular disease. Studies in cell culture and animal models, as well as a limited number of clinical studies, reveal the lipid-lowering, insulin-sensitizing, antihypertensive, and anti-inflammatory properties of citrus flavonoids. In animal models, supplementation of rodent diets with citrus flavonoids prevents hepatic steatosis, dyslipidemia, and insulin resistance primarily through inhibition of hepatic fatty acid synthesis and increased fatty acid oxidation. Citrus flavonoids blunt the inflammatory response in metabolically important tissues including liver, adipose, kidney, and the aorta. The mechanisms underlying flavonoid-induced metabolic regulation have not been completely established, although several potential targets have been identified. In mouse models, citrus flavonoids show marked suppression of atherogenesis through improved metabolic parameters as well as through direct impact on the vessel wall. Recent studies support a role for citrus flavonoids in the treatment of dyslipidemia, insulin resistance, hepatic steatosis, obesity, and atherosclerosis. Larger human studies examining dose, bioavailability, efficacy, and safety are required to promote the development of these promising therapeutic agents.