tbuckley/cabot-search huggingface dataset:
Urologists' Use of Intensity-Modulated Radiation Therapy for Prostate Cancer
Authors: Jean M. Mitchell
Journal: New England Journal of Medicine (2013)

Some urology groups have integrated intensity-modulated radiation therapy (IMRT), a radiation treatment with a high reimbursement rate, into their practice. This is permitted by the exception for in-office ancillary services in the federal prohibition against self-referral. I examined the association between ownership of IMRT services and use of IMRT to treat prostate cancer.Using Medicare claims from 2005 through 2010, I constructed two samples: one comprising 35 self-referring urology groups in private practice and a matched control group comprising 35 non-self-referring urology groups in private practice, and the other comprising non-self-referring urologists employed at 11 National Comprehensive Cancer Network centers matched with 11 self-referring urology groups in private practice. I compared the use of IMRT in the periods before and during ownership and used a difference-in-differences analysis to evaluate changes in IMRT use according to self-referral status.The rate of IMRT use by self-referring urologists in private practice increased from 13.1 to 32.3%, an increase of 19.2 percentage points (P<0.001). Among non-self-referring urologists, the rate of IMRT use increased from 14.3 to 15.6%, an increase of 1.3 percentage points (P=0.05). The unadjusted difference-in-differences effect was 17.9 percentage points (P<0.001). The regression-adjusted increase in IMRT use associated with self-referral was 16.4 percentage points (P<0.001). The rate of IMRT use by urologists working at National Comprehensive Cancer Network centers remained stable at 8.0% but increased by 33.0 percentage points among the 11 matched self-referring urology groups. The regression-adjusted difference-in-differences effect was 29.3 percentage points (P<0.001).Urologists who acquired ownership of IMRT services increased their use of IMRT substantially more than urologists who did not own such services. Allowing urologists to self-refer for IMRT may contribute to increased use of this expensive therapy. (Funded by the American Society for Radiation Oncology.).
HDL and cholesterol handling in the brain
Authors: Cecilia Vitali, Cheryl L Wellington, Laura Calabresi
Journal: Cardiovascular Research (2014)

Cholesterol is an essential component of both the peripheral nervous system and central nervous system (CNS) of mammals. Brain cholesterol is synthesized in situ by astrocytes and oligodendrocytes and is almost completely isolated from other pools of cholesterol in the body, but a small fraction can be taken up from the circulation as 27-hydroxycholesterol, or via the scavenger receptor class B type I. Glial cells synthesize native high-density lipoprotein (HDL)-like particles, which are remodelled by enzymes and lipid transfer proteins, presumably as it occurs in plasma. The major apolipoprotein constituent of HDL in the CNS is apolipoprotein E, which is produced by astrocytes and microglia. Apolipoprotein A-I, the major protein component of plasma HDL, is not synthesized in the CNS, but can enter and become a component of CNS lipoproteins. Low HDL-C levels have been shown to be associated with cognitive impairment and various neurodegenerative diseases. On the contrary, no clear association with brain disorders has been shown in genetic HDL defects, with the exception of Tangier disease. Mutations in a wide variety of lipid handling genes can result in human diseases, often with a neuronal phenotype caused by dysfunctional intracellular lipid trafficking.
Reduced FOXP3+ regulatory T cells in patients with primary sclerosing cholangitis are associated with IL2RA gene polymorphisms
Authors: Marcial Sebode, Moritz Peiseler, Björn Franke, Dorothee Schwinge, Tanja Schoknecht, Frederike Wortmann, Alexander Quaas, Britt-Sabina Petersen, Eva Ellinghaus, Udo Baron, Sven Olek, Christiane Wiegard, Christina Weiler-Normann, Ansgar W. Lohse, Johannes Herkel, Christoph Schramm
Journal: Journal of Hepatology (2014)
The Relationship Between Alcohol Consumption and Vascular Complications and Mortality in Individuals With Type 2 Diabetes
Authors: Juuso I. Blomster, Sophia Zoungas, John Chalmers, Qiang Li, Clara K. Chow, Mark Woodward, Giuseppe Mancia, Neil Poulter, Bryan Williams, Stephen Harrap, Bruce Neal, Anushka Patel, Graham S. Hillis
Journal: Diabetes Care (2014)

Moderate alcohol consumption has been associated with a reduced risk of mortality and coronary artery disease. The relationship between cardiovascular health and alcohol use in type 2 diabetes is less clear. The current study assesses the effects of alcohol use among participants in the Action in Diabetes and Vascular Disease: Preterax and Diamicron Modified-Release Controlled Evaluation (ADVANCE) trial.The effects of alcohol use were explored using Cox regression models, adjusted for potential confounders. The study end points were cardiovascular events (cardiovascular death, myocardial infarction, and stroke), microvascular complications (new or worsening nephropathy or retinopathy), and all-cause mortality.During a median of 5 years of follow-up, 1,031 (9%) patients died, 1,147 (10%) experienced a cardiovascular event, and 1,136 (10%) experienced a microvascular complication. Compared with patients who reported no alcohol consumption, those who reported moderate consumption had fewer cardiovascular events (adjusted hazard ratio [aHR] 0.83; 95% CI 0.72-0.95; P = 0.008), less microvascular complications (aHR 0.85; 95% CI 0.73-0.99; P = 0.03), and lower all-cause mortality (aHR 0.87; 96% CI 0.75-1.00; P = 0.05). The benefits were particularly evident in participants who drank predominantly wine (cardiovascular events aHR 0.78, 95% CI 0.63-0.95, P = 0.01; all-cause mortality aHR 0.77, 95% CI 0.62-0.95, P = 0.02). Compared with patients who reported no alcohol consumption, those who reported heavy consumption had dose-dependent higher risks of cardiovascular events and all-cause mortality.In patients with type 2 diabetes, moderate alcohol use, particularly wine consumption, is associated with reduced risks of cardiovascular events and all-cause mortality.
Prospective Study of Moderate Alcohol Consumption and Risk of Peripheral Arterial Disease in US Male Physicians
Authors: Carlos A. Camargo, Meir J. Stampfer, Robert J. Glynn, J. Michael Gaziano, JoAnn E. Manson, Samuel Z. Goldhaber, Charles H. Hennekens
Journal: Circulation (1997)

Background Moderate alcohol consumption decreases the risk of coronary heart disease, but its relation to peripheral arterial disease (PAD) is uncertain. Methods and Results In the Physicians' Health Study, a randomized trial of the use of aspirin and β-carotene in 22 071 apparently healthy men, we documented 433 incident cases of PAD during 11 years of follow-up. After we controlled for age and treatment assignment, daily drinkers (≥7 drinks per week) had a relative risk (RR) of PAD of 0.92 (95% confidence interval, 0.72 to 1.17) compared with the reference group (&lt;1 drink per week). After additional control for smoking, however, the RR was 0.68 (0.52 to 0.89). Further control for exercise, diabetes mellitus, and parental history of myocardial infarction revealed an RR of 0.74 (0.57 to 0.97). Conclusions Moderate alcohol consumption appears to decrease the risk of PAD in apparently healthy men.
Impact of erectile dysfunction and its subsequent treatment with sildenafil: qualitative study
Authors: John Tomlinson, David Wright
Journal: BMJ (2004)

Objectives To determine the effects of erectile dysfunction and to explore the impact of treatment with sildenafil (Viagra). Design An exploratory qualitative study with semistructured interviews. Setting Men's health clinic in NHS hospital. Participants 40 men who had had erectile dysfunction and had attended the clinic during the year before interview. Main outcome measures Impact of erectile dysfunction on men, their expectations ofsildenafil, and impact of treatment on men and their relationships. Issues explored with exploratory qualitative approach. Results Erectile dysfunction caused serious distress to all those men who experienced it, with marked effects on their self esteem and their relationships. Sildenafil, when it worked, caused a great improvement in wellbeing. The expectations raised by media hyperbole with the launch of sildenafil had an adverse effect on the morale of those who found it did not work. When, according to the patient, treatment did not work, the distress was severe and for many confirmed their lack of self worth. Conclusions Further study is needed to explore the feelings of men affected by erectile dysfunction and their perception of treatment. Health professionals should be aware of the extreme distress erectile dysfunction can cause.
Do pregnant women follow exercise guidelines? Prevalence data among 3482 women, and prediction of low-back pain, pelvic girdle pain and depression
Authors: Kristin Gjestland, Kari Bø, Katrine Mari Owe, Malin Eberhard-Gran
Journal: British Journal of Sports Medicine (2012)

Purpose We describe exercise level in mid-pregnancy, associated sociodemographic variables, and investigate the association between exercise in mid-pregnancy and subsequent low-back pain, pelvic girdle pain and depression at 32 weeks of pregnancy. Material and methods The study included 3482 pregnant women participating in the Akershus Birth Cohort study (response rate 80.5%). Data were collected by a questionnaire in pregnancy weeks 17–21, pregnancy week 32 and electronic birth journal. The results were analysed by logistic regression and are presented as crude (cOR) and adjusted OR (aOR) with 95% CI. Results Only 14.6% of the respondents followed the current exercise prescription for exercise during pregnancy (≥3 times a week, &gt;20 min at moderate intensity). One-third of the study sample exercised less than once a week at pregnancy weeks 17–21. Women exercising either 1–2 times or ≥3 times a week at mid-pregnancy were more often primiparous, higher-educated and had less often prepregnacy body mass index &gt;30 kg/m 2 compared with women exercising less than once a week. Women who exercised ≥3 times a week were less likely to report pelvic girdle pain (aOR: 0.76, 95% CI 0.61 to 0.96), while women exercising 1–2 times a week were less likely to report low-back pain (aOR: 0.80, 95% CI 0.66 to 0.97) and depression (aOR: 0.66, 95% CI 0.48 to 0.91). Conclusions Few Norwegian women follow current exercise prescriptions for exercise in mid-pregnancy. The results may indicate an association between exercising mid-pregnancy and lower prevalence of low-back pain, pelvic girdle pain and depression in late pregnancy.
The repertoire of T-lymphocytes recovered by bronchoalveolar lavage from healthy nonsmokers
Authors: SE Burastero, B Borgonovo, D Gaffi, E Frittoli, A Wack, GA Rossi, E Crimi
Journal: European Respiratory Journal (1996)

We reasoned that persistent exposure to a limited set of airborne antigens could drive the preferential expansion of single T-cell clones in the lower respiratory tract of normal individuals. To explore this issue, the normal human alpha/beta T-cell receptor repertoire was studied in lung lymphocytes obtained by bronchoalveolar lavage (BAL) from the humen of the lower respiratory tract. BAL T-cells obtained from five healthy volunteers were first analysed using polymerase chain reaction to amplify all known V alpha and V beta genes of the T-cell receptor. T-cells from peripheral blood were used as an internal control. Heteroduplex analysis of the amplified products was then performed, to assess the clonal composition of the repertoire of lung- versus blood-derived T-lymphocytes within each amplified variable gene family. In all subjects, the T-cell repertoire in the lung was largely as heterogeneous as peripheral blood in terms of clonal composition. This indicated lack of preferential expansion of single T-cell clones. A few T-cell clones were simultaneously expanded in blood and lung in all individuals within a limited number of V beta (mean 2.4; range 2-4) and V alpha (mean 1.6; range 1-3) genes. We also found that lung T-lymphocytes expressed all of the V gene families of the T-cell receptor that were expressed by peripheral blood T-cells. Our results indicate that T-cell clones in the lower respiratory tract of normal individuals are distributed according to a largely polyclonal pattern, which corresponds to that found in peripheral blood.
Nucleotide Polymorphism at a Gene (Pgi) under Balancing Selection in a Butterfly Metapopulation
Authors: C. W. Wheat, C. R. Haag, J. H. Marden, I. Hanski, M. J. Frilander
Journal: Molecular Biology and Evolution (2009)

The Glanville fritillary butterfly (Melitaea cinxia, Nymphalidae) has a large, well-studied metapopulation in the Aland Islands in Finland. Previous studies have found that the common allozyme genotypes at the phosphoglucose isomerase (PGI) locus are associated with individual variation in performance and fitness, with phenotypic data suggesting ongoing balancing selection via heterozygote advantage. Here, we analyze nucleotide polymorphism in the coding region of the Pgi gene. Pgi is exceptionally polymorphic, in contrast to three other metabolic genes (Mdh, Idh, and Gapdh) with low levels of polymorphism. Most of the variation is due to two common haplotype clades, which are highly divergent and exhibit extensive linkage disequilibrium. These two clades correspond to the two most common allozyme alleles previously studied. Molecular tests of selection and coalescence simulations indicate that patterns of nucleotide polymorphism depart from neutrality and are consistent with long-term balancing selection. The split between the two main haplotype clades is estimated to predate the last common ancestor of a clade of five extant Melitaea species. Comparative structural analysis of Pgi polymorphism in M. cinxia and the unrelated Colias eurytheme butterfly suggests a similar but not identical target of balancing selection. Our results indicate convergent evolution between these two species at both the phenotypic and molecular levels.
Phase I Trial of Bortezomib (PS-341; NSC 681239) and “Nonhybrid” (Bolus) Infusion Schedule of Alvocidib (Flavopiridol; NSC 649890) in Patients with Recurrent or Refractory Indolent B-cell Neoplasms
Authors: Beata Holkova, Maciej Kmieciak, E. Brent Perkins, Prithviraj Bose, Rachid C. Baz, G. David Roodman, Robert K. Stuart, Viswanathan Ramakrishnan, Wen Wan, Cody J. Peer, Jana Dawson, Loveleen Kang, Connie Honeycutt, Mary Beth Tombes, Ellen Shrader, Caryn Weir-Wiggins, Martha Wellons, Heidi Sankala, Kevin T. Hogan, A. Dimitrios Colevas, L. Austin Doyle, William D. Figg, Domenico Coppola, John D. Roberts, Daniel Sullivan, Steven Grant
Journal: Clinical Cancer Research (2014)

Abstract Purpose: This phase I study was conducted to determine the dose-limiting toxicities (DLT) and maximum tolerated dose (MTD) for the combination of bortezomib and alvocidib in patients with B-cell malignancies (multiple myeloma, indolent lymphoma, Waldenstrom macroglobulinemia, and mantle cell lymphoma). Experimental Design: Patients received bortezomib (intravenous push), followed by alvocidib (1-hour infusion), on days 1, 4, 8, and 11 of a 21-day treatment cycle. Patients experiencing responses or stable disease continued on treatment at the investigator's discretion. A standard 3+3 dose-escalation design was used to identify the MTD based on DLTs, and pharmacokinetic and pharmacodynamic studies were conducted. Results: A total of 44 patients were enrolled, with 39 patients assessed for response. The MTD was established as 1.3 mg/m2 for bortezomib and 40 mg/m2 for alvocidib. The most common hematologic toxicities included leukopenia, lymphopenia, neutropenia, and thrombocytopenia. The most common nonhematologic toxicities included diarrhea, fatigue, and sensory neuropathy. Three complete remissions (8%) and 10 partial remissions (26%) were observed for a total response rate of 33%. Pharmacokinetic findings with the current dosing regimen were consistent with the comparable literature and the hybrid dosing regimen. Pharmacodynamic study results did not correlate with clinical responses. Conclusions: The combination of bortezomib and alvocidib is tolerable, and an MTD has been established for this schedule. The regimen appears to be efficacious in patients with relapsed/refractory multiple myeloma or indolent non-Hodgkin lymphoma. As the nonhybrid regimen is less cumbersome than the previous hybrid dosing schedule regimen, the current schedule is recommended for successor studies. Clin Cancer Res; 20(22); 5652–62. ©2014 AACR.
Early Retinal Arteriolar Changes and Peripheral Neuropathy in Diabetes
Authors: Jie Ding, Carol Y. Cheung, M. Kamran Ikram, Ying-Feng Zheng, Ching-Yu Cheng, Ecosse L. Lamoureux, E. Shyong Tai, Tavintharan Subramaniam, Tien Yin Wong
Journal: Diabetes Care (2012)

OBJECTIVE To examine the association between early retinal arteriolar abnormalities and diabetic peripheral neuropathy (DPN). RESEARCH DESIGN AND METHODS Data from 608 people (aged 40–80 years) with diabetes from the population-based Singapore Malay Eye Study were analyzed. Participants underwent binocular two-field digital retinal photography and quantitative sensory testing. DPN was defined as an abnormal response to a monofilament or neurothesiometer test. Quantitative changes of retinal vascular caliber and arteriolar bifurcation geometry were measured using a computer-based program. Qualitative retinal signs of retinopathy and retinal arteriolar wall signs were graded by standardized methods. RESULTS DPN was present in 155 people (25.5%). After adjusting for age, sex, diabetes duration, HbA1c, cardiovascular risk factors, antihypertensive medication use, and peripheral arterial disease, people with suboptimal arteriolar caliber (odds ratio 1.94 [95% CI 1.22–3.10]), larger arteriolar branching coefficient (1.58 [1.03–2.42]), diabetic retinopathy (1.82 [1.20–2.75]), and focal arteriolar narrowing (2.92 [1.48–5.76]) were more likely to have DPN. Participants with a greater number of retinal microvascular signs were more likely to have DPN than those without retinal changes (6.11 [2.11–17.71] for two or more signs and 3.47 [1.18–10.21] for one sign compared with none). CONCLUSIONS Individuals with diabetes with early retinal arteriolar abnormalities are more likely to have DPN, independent of hyperglycemia and major vascular risk factors. These data support the hypothesis that early microvascular dysfunction, evident in the retina, is an independent risk factor for DPN.
Lung Cancer Survival and Functional Polymorphisms in MBL2, an Innate-Immunity Gene
Authors: Sharon R. Pine, Leah E. Mechanic, Stefan Ambs, Elise D. Bowman, Stephen J. Chanock, Christopher Loffredo, Peter G. Shields, Curtis C. Harris
Journal: JNCI Journal of the National Cancer Institute (2007)

The relationship among chronic inflammation, innate immunity, and cancer is well established. Mannose-binding lectin (MBL) is a key player in innate immunity. Five polymorphisms in the promoter and first exon of the MBL2 gene alter the expression and function of MBL in humans and are associated with inflammation-related disease susceptibility. These five polymorphisms create six well-characterized haplotypes that result in lower (i.e., LYB, LYC, HYD, and LXA) or higher (i.e., HYA and LYA) serum MBL concentrations. We investigated whether survival of patients with lung cancer was associated with these polymorphisms.We used a multivariable Cox proportional hazards model to study the association between MBL2 polymorphisms and their haplotypes and diplotypes in 558 white and 173 African American patients with non-small-cell lung cancer in the Baltimore, MD, area and lung cancer mortality. Smoking history and race were obtained from interviews, tumor stage was obtained from medical records, and cause of death was obtained from the National Death Index. All statistical tests were two-sided.We found a statistically significant association between the X allele of the promoter Y/X polymorphism (which results in a lower serum MBL concentration) and improved lung cancer survival among white patients (risk ratio [RR] of death from lung cancer with X/X or X/Y genotype compared with Y/Y genotype = 0.61, 95% confidence interval [CI] = 0.46 to 0.81) but not among African American patients (RR = 1.11, 95% CI = 0.69 to 1.77). The associations among white patients were strongest in heavy smokers and were independent of stage. We also found a statistically significant interaction between the Y/X polymorphism and race for lung cancer survival (P(interaction) = .019). The MBL2 LXA haplotype and XA/B diplotype, which are also associated with low serum MBL levels, were statistically significantly associated with improved lung cancer survival among white patients.The functional Y/X polymorphism of the innate-immunity gene MBL2 and MBL2 haplotypes and diplotypes appear to be associated with lung cancer survival among white patients.
High-Level Expression of Chemokine CXCL16 by Tumor Cells Correlates with a Good Prognosis and Increased Tumor-Infiltrating Lymphocytes in Colorectal Cancer
Authors: Shozo Hojo, Keiichi Koizumi, Koichi Tsuneyama, Yoshihisa Arita, Zhengguo Cui, Kanna Shinohara, Takayuki Minami, Isaya Hashimoto, Takashi Nakayama, Hiroaki Sakurai, Yasuo Takano, Osamu Yoshie, Kazuhiro Tsukada, Ikuo Saiki
Journal: Cancer Research (2007)

CXCL16 is a new member of the chemokine superfamily, which exists in a transmembrane as well as a soluble form. Its receptor CXCR6 is detected on CD4(+) T cells, CD8(+) T cells, and natural killer T cells. Here, we report a significant correlation of CXCL16 expression by tumor cells with the infiltration of T cells and prognosis in colorectal cancer (CRC). We first found that CXCL16 expression was consistently up-regulated more in tumor tissues than in normal mucosa derived from the same CRC patients. Four human CRC cell lines also expressed CXCL16 mRNA and secreted soluble CXCL16. We next examined the expression of CXCL16 and infiltration of lymphocytes in CRC specimens (n = 58) by immunohistochemistry. CRC patients with high levels of CXCL16 expression (n = 43) had higher levels of CD4(+) and CD8(+) tumor-infiltrating lymphocytes (TIL; P < 0.01) than those with low levels of CXCL16 expression (n = 15). Furthermore, the high CXCL16 expression group showed significantly better prognosis than the low CXCL16 expression group (P < 0.05). Collectively, our data suggest that the expression of CXCL16 by tumor cells enhances the recruitment of TILs, thereby bringing about a better prognosis in CRC. Thus, CXCL16 is a new prognostic biomarker and may be useful for the development of a more effective therapeutic strategy for CRC.