tbuckley/cabot-search huggingface dataset:
Dietary Management of the Malabsorption Syndrome
Authors: E M UPTON, B A McLAREN
Journal: JAMA (1963)

The purpose of this report is to emphasize the importance of strict dietary control of patients suffering from the malabsorption syndrome and to announce the availability of a gluten-free bread-substitute, called "Unimix", from the Scientific Development Committee, Room 14, Medical Building, University of Toronto. Science a gluten-free diet is difficult to follow because of the widespread use of wheat flour and other cereals in the production of many common foods, a suggested gluten-free meal pattern is presented, which conforms with Canada's Food Guide and permits a number of choices of menu within certain limits.
Desensitization to Methylprednisolone Succinate in a Patient with Multiple Sclerosis
Authors: Denisse Angel Pereira, Ricardo Madrigal-Burgaleta, Pilar Berges, Maria Alicia Urena Tavera, Ximena Rodríguez, Emilio Alvarez-Cuesta
Journal: Journal of Allergy and Clinical Immunology (2013)
Autoantibodies From Single Circulating Plasmablasts React With Citrullinated Antigens and <i>Porphyromonas gingivalis</i> in Rheumatoid Arthritis
Authors: Song Li, Yangsheng Yu, Yinshi Yue, Hongyan Liao, Wanqin Xie, Jessica Thai, Ted R. Mikuls, Geoffrey M. Thiele, Michael J. Duryee, Harlan Sayles, Jeffrey B. Payne, Lynell W. Klassen, James R. O'Dell, Zhixin Zhang, Kaihong Su
Journal: Arthritis & Rheumatology (2015)

Anti-citrullinated protein antibodies (ACPAs) are highly specific for rheumatoid arthritis (RA). However, the molecular basis for ACPA production is still unclear. The purpose of this study was to determine if circulating plasmablasts from RA patients produce ACPAs and whether Porphyromonas gingivalis facilitates the generation of ACPAs.Using a single-cell antibody cloning approach, we generated 217 and 110 monoclonal recombinant antibodies from circulating plasmablasts from 7 RA patients and 4 healthy controls, respectively. Antibody reactivity with citrullinated antigens was tested by a second-generation anti-cyclic citrullinated peptide (anti-CCP) kit and by enzyme-linked immunosorbent assays (ELISAs) against citrullinated human antigens. Antibody reactivity with P gingivalis was tested by ELISAs against outer membrane antigens (OMAs) and citrullinated enolase from P gingivalis.Approximately 19.5% of plasmablast-derived antibodies from anti-CCP-positive RA patients, but none from 1 anti-CCP-negative RA patient or the healthy controls, specifically recognized citrullinated antigens. The immunoglobulin genes encoding these ACPAs were highly mutated, with increased ratios of replacement mutations to silent mutations, suggesting the involvement of active antigen selection in ACPA generation. Interestingly, 63% of the ACPAs cross-reacted with OMAs and/or citrullinated enolase from P gingivalis. The reactivity of ACPAs against citrullinated proteins from P gingivalis was confirmed by immunoblotting and mass spectrometry. Furthermore, some germline-reverted ACPAs retained their reactivity with P gingivalis antigens but completely lost their reactivity with citrullinated human antigens.These results suggest that circulating plasmablasts in RA patients produce ACPAs and that this process may be facilitated by anti-P gingivalis immune responses.
Selective Serotonin Reuptake Inhibitors and Violent Crime: A Cohort Study
Authors: Yasmina Molero, Paul Lichtenstein, Johan Zetterqvist, Clara Hellner Gumpert, Seena Fazel
Journal: PLoS Medicine (2015)

Background Although selective serotonin reuptake inhibitors (SSRIs) are widely prescribed, associations with violence are uncertain. Methods and Findings From Swedish national registers we extracted information on 856,493 individuals who were prescribed SSRIs, and subsequent violent crimes during 2006 through 2009. We used stratified Cox regression analyses to compare the rate of violent crime while individuals were prescribed these medications with the rate in the same individuals while not receiving medication. Adjustments were made for other psychotropic medications. Information on all medications was extracted from the Swedish Prescribed Drug Register, with complete national data on all dispensed medications. Information on violent crime convictions was extracted from the Swedish national crime register. Using within-individual models, there was an overall association between SSRIs and violent crime convictions (hazard ratio [HR] = 1.19, 95% CI 1.08–1.32, p < 0.001, absolute risk = 1.0%). With age stratification, there was a significant association between SSRIs and violent crime convictions for individuals aged 15 to 24 y (HR = 1.43, 95% CI 1.19–1.73, p < 0.001, absolute risk = 3.0%). However, there were no significant associations in those aged 25–34 y (HR = 1.20, 95% CI 0.95–1.52, p = 0.125, absolute risk = 1.6%), in those aged 35–44 y (HR = 1.06, 95% CI 0.83–1.35, p = 0.666, absolute risk = 1.2%), or in those aged 45 y or older (HR = 1.07, 95% CI 0.84–1.35, p = 0.594, absolute risk = 0.3%). Associations in those aged 15 to 24 y were also found for violent crime arrests with preliminary investigations (HR = 1.28, 95% CI 1.16–1.41, p < 0.001), non-violent crime convictions (HR = 1.22, 95% CI 1.10–1.34, p < 0.001), non-violent crime arrests (HR = 1.13, 95% CI 1.07–1.20, p < 0.001), non-fatal injuries from accidents (HR = 1.29, 95% CI 1.22–1.36, p < 0.001), and emergency inpatient or outpatient treatment for alcohol intoxication or misuse (HR = 1.98, 95% CI 1.76–2.21, p < 0.001). With age and sex stratification, there was a significant association between SSRIs and violent crime convictions for males aged 15 to 24 y (HR = 1.40, 95% CI 1.13–1.73, p = 0.002) and females aged 15 to 24 y (HR = 1.75, 95% CI 1.08–2.84, p = 0.023). However, there were no significant associations in those aged 25 y or older. One important limitation is that we were unable to fully account for time-varying factors. Conclusions The association between SSRIs and violent crime convictions and violent crime arrests varied by age group. The increased risk we found in young people needs validation in other studies.
2 month evening and night closed-loop glucose control in patients with type 1 diabetes under free-living conditions: a randomised crossover trial
Authors: Jort Kropff, Simone Del Favero, Jerome Place, Chiara Toffanin, Roberto Visentin, Marco Monaro, Mirko Messori, Federico Di Palma, Giordano Lanzola, Anne Farret, Federico Boscari, Silvia Galasso, Paolo Magni, Angelo Avogaro, Patrick Keith-Hynes, Boris P Kovatchev, Daniela Bruttomesso, Claudio Cobelli, J Hans DeVries, Eric Renard, Lalo Magni
Journal: The Lancet Diabetes & Endocrinology (2015)
Long-Term Effects of Frequent In–Center Hemodialysis
Authors: Glenn M. Chertow, Nathan W. Levin, Gerald J. Beck, John T. Daugirdas, Paul W. Eggers, Alan S. Kliger, Brett Larive, Michael V. Rocco, Tom Greene
Journal: Journal of the American Society of Nephrology (2015)

The Frequent Hemodialysis Network Daily Trial randomized 245 patients to receive six (frequent) or three (conventional) in–center hemodialysis sessions per week for 12 months. As reported previously, frequent in–center hemodialysis yielded favorable effects on the coprimary composite outcomes of death or change in left ventricular mass and death or change in self–reported physical health. Here, we determined the long-term effects of the 12-month frequent in–center hemodialysis intervention. We determined the vital status of patients over a median of 3.6 years (10%–90% range, 1.5–5.3 years) after randomization. Using an intention to treat analysis, we compared the mortality hazard in randomized groups. In a subset of patients from both groups, we reassessed left ventricular mass and self–reported physical health a year or more after completion of the intervention; 20 of 125 patients (16%) randomized to frequent hemodialysis died during the combined trial and post–trial observation periods in contrast to 34 of 120 patients (28%) randomized to conventional hemodialysis. The relative mortality hazard for frequent versus conventional hemodialysis was 0.54 (95% confidence interval, 0.31 to 0.93); with censoring of time after kidney transplantation, the relative hazard was 0.56 (95% confidence interval, 0.32 to 0.99). Bayesian analysis suggested a relatively high probability of clinically significant benefit and a very low probability of harm with frequent hemodialysis. In conclusion, a 12-month frequent in–center hemodialysis intervention significantly reduced long-term mortality, suggesting that frequent hemodialysis may benefit selected patients with ESRD.
The herbal medicine black cohosh increases the cytotoxicity of doxorubicin to breast cancer cells by inhibiting doxorubicin efflux
Authors: Iwona Dobrucki, Susan Higgins, Sara Rockwell
Journal: Cancer Research (2008)

2303  Despite the lack of rigorous studies examining the efficacy and safety of black cohosh (BC), many breast cancer patients use this herbal alternative medicine while receiving chemotherapy. We showed previously that BC increases the cytotoxicity of doxorubicin to breast cancer cells in vitro (Breast Cancer Res Treat, 90:233-239, 2005); this sensitization increased with the BC dose but was significant at BC doses in the range used by some women. The studies presented here test the hypothesis that BC modulates the effect of doxorubicin by altering the uptake or efflux of this drug.  All studies were performed using EMT6 mouse mammary tumor cells. A standardized liquid commercial extract of BC (Gaia) was used at a concentration estimated to be equivalent to 100x the human dose; control cultures were treated with the vehicle for this extract. For transport studies, suspension cultures were preincubated for 6 h with BC extract or vehicle, then doxorubicin (10 or 100 µg/mL) was added and cells were incubated for an additional 2 h. Cells were collected at frequent intervals during doxorubicin treatment, spun through oil, collected, washed and lysed; the released cell-associated doxorubicin was measured by spectrofluorometry. Doxorubicin levels in cells were calculated using cell counts assessed with a Coulter Counter. At the end of the 2 h uptake period, cells were collected by centrifugation, washed and resuspended in culture medium containing BC or vehicle. Cell-associated doxorubicin was measured at frequent intervals over the next 3 h to assess drug efflux.  The concentration of cell-associated doxorubicin increased progressively throughout the 2 h incubation; uptake was indistinguishable in BC treated and control cells. However, BC decreased the efflux of doxorubicin, resulting in about 40% higher levels of cell-associated drug at the end of efflux.  Cytotoxicity studies were performed to test the hypothesis that changes in efflux were responsible for the sensitizing effect of BC. Cells were incubated with BC (or vehicle) before, during, or after treatment with 1.6 μg/mL doxorubicin then assayed for survival using a clonogenic assay. Preincubation with BC for 2-24 h before doxorubicin treatment or co-incubation with BC during doxorubicin treatment had no significant effects on doxorubicin cytotoxicity. However, incubation with BC after doxorubicin treatment markedly reduced cell survival; this effect increased as the duration of BC treatment increased from 2 to 24 h.  These studies indicate that the increased sensitivity of BC-treated cells to doxorubicin reflects BC-induced changes in drug efflux. Further studies are in progress to elucidate the mechanism underlying the effect and to examine its potential clinical implications using doxorubicin-sensitive and -resistant human and murine cell lines.  Supported by grant BCT R0503838 from the Susan G. Komen Cancer Foundation
Restoring Anticancer Immune Response by Targeting Tumor-Derived Exosomes With a HSP70 Peptide Aptamer
Authors: Jessica Gobbo, Guillaume Marcion, Marine Cordonnier, Alexandre M. M. Dias, Nicolas Pernet, Arlette Hammann, Sarah Richaud, Hajare Mjahed, Nicolas Isambert, Victor Clausse, Cédric Rébé, Aurélie Bertaut, Vincent Goussot, Frédéric Lirussi, François Ghiringhelli, Aurélie de Thonel, Pierre Fumoleau, Renaud Seigneuric, Carmen Garrido
Journal: JNCI Journal of the National Cancer Institute (2015)

Exosomes, via heat shock protein 70 (HSP70) expressed in their membrane, are able to interact with the toll-like receptor 2 (TLR2) on myeloid-derived suppressive cells (MDSCs), thereby activating them. We analyzed exosomes from mouse (C57Bl/6) and breast, lung, and ovarian cancer patient samples and cultured cancer cells with different approaches, including nanoparticle tracking analysis, biolayer interferometry, FACS, and electron microscopy. Data were analyzed with the Student's t and Mann-Whitney tests. All statistical tests were two-sided. We showed that the A8 peptide aptamer binds to the extracellular domain of membrane HSP70 and used the aptamer to capture HSP70 exosomes from cancer patient samples. The number of HSP70 exosomes was higher in cancer patients than in healthy donors (mean, ng/mL ± SD = 3.5±1.7 vs 0.17±0.11, respectively, P = .004). Accordingly, all cancer cell lines examined abundantly released HSP70 exosomes, whereas "normal" cells did not. HSP70 had higher affinity for A8 than for TLR2; thus, A8 blocked HSP70/TLR2 association and the ability of tumor-derived exosomes to activate MDSCs. Treatment of tumor-bearing C57Bl/6 mice with A8 induced a decrease in the number of MDSCs in the spleen and inhibited tumor progression (n = 6 mice per group). Chemotherapeutic agents such as cisplatin or 5FU increase the amount of HSP70 exosomes, favoring the activation of MDSCs and hampering the development of an antitumor immune response. In contrast, this MDSC activation was not observed if cisplatin or 5FU was combined with A8. As a result, the antitumor effect of the drugs was strongly potentiated. A8 might be useful for quantifying tumor-derived exosomes and for cancer therapy through MDSC inhibition.
Growth Factors and Cytokines in Bone Cell Metabolism
Authors: E Canalis, T L McCarthy, M Centrella
Journal: Annual Review of Medicine (1991)

Growth factors regulate the growth and differentiated function of cells. Skeletal cells synthesize fibroblast growth factor, platelet-derived growth factor, insulin-like growth factor, transforming growth factor beta, and additional cytokines. Some of the growth factors produced by bone cells primarily stimulate bone cell replication, whereas others also affect the differentiated function of the osteoblast. Skeletal growth factors also may play a role in the pathogenesis and therapy of metabolic bone disease.
Germline Variants in Asporin Vary by Race, Modulate the Tumor Microenvironment, and Are Differentially Associated with Metastatic Prostate Cancer
Authors: Paula J. Hurley, Debasish Sundi, Brian Shinder, Brian W. Simons, Robert M. Hughes, Rebecca M. Miller, Benjamin Benzon, Sheila F. Faraj, George J. Netto, Ismael A. Vergara, Nicholas Erho, Elai Davicioni, R. Jeffrey Karnes, Guifang Yan, Charles Ewing, Sarah D. Isaacs, David M. Berman, Jennifer R. Rider, Kristina M. Jordahl, Lorelei A. Mucci, Jessie Huang, Steven S. An, Ben H. Park, William B. Isaacs, Luigi Marchionni, Ashley E. Ross, Edward M. Schaeffer
Journal: Clinical Cancer Research (2015)

Abstract Purpose: Prostate cancers incite tremendous morbidity upon metastatic growth. We previously identified Asporin (ASPN) as a potential mediator of metastatic progression found within the tumor microenvironment. ASPN contains an aspartic acid (D)-repeat domain and germline polymorphisms in D-repeat-length have been associated with degenerative diseases. Associations of germline ASPN D polymorphisms with risk of prostate cancer progression to metastatic disease have not been assessed. Experimental Design: Germline ASPN D-repeat-length was retrospectively analyzed in 1,600 men who underwent radical prostatectomy for clinically localized prostate cancer and in 548 noncancer controls. Multivariable Cox proportional hazards models were used to test the associations of ASPN variations with risk of subsequent oncologic outcomes, including metastasis. Orthotopic xenografts were used to establish allele- and stroma-specific roles for ASPN D variants in metastatic prostate cancer. Results: Variation at the ASPN D locus was differentially associated with poorer oncologic outcomes. ASPN D14 [HR, 1.72; 95% confidence interval (CI), 1.05–2.81, P = 0.032] and heterozygosity for ASPN D13/14 (HR, 1.86; 95% CI, 1.03–3.35, P = 0.040) were significantly associated with metastatic recurrence, while homozygosity for the ASPN D13 variant was significantly associated with a reduced risk of metastatic recurrence (HR, 0.44; 95% CI, 0.21–0.94, P = 0.035) in multivariable analyses. Orthotopic xenografts established biologic roles for ASPN D14 and ASPN D13 variants in metastatic prostate cancer progression that were consistent with patient-based data. Conclusions: We observed associations between ASPN D variants and oncologic outcomes, including metastasis. Our data suggest that ASPN expressed in the tumor microenvironment is a heritable modulator of metastatic progression. Clin Cancer Res; 22(2); 448–58. ©2015 AACR.
Effect of discussion and deliberation on public's views of priority setting
Authors: B. Hanratty, D. Lawlor, P. Dolan, R. Cookson, B. Ferguson
Journal: BMJ (1999)

Cholesterol lowering margarine may not be useful in healthy fat modified dietEditor-A new margarine spread that reduces intestinal absorption of cholesterol was launched in the United Kingdom in April. 1 Benecol contains stanol esters derived from wood pulp.National press advertisements indicate that it reduces serum concentrations of low density lipoprotein cholesterol by an average of 14% when taken as three servings daily as part of a healthy diet.This is based on the findings of a study of mildly hypercholesterolaemic subjects in North Karelia, Finland. 2 During this study, intake of dietary fat was about 35% of total energy intake and cholesterol intake above 300 mg per day.A mean reduction in total cholesterol concentration of 7.4% was achieved after 6 months and of 10.2% after 12 months.Such a 10% reduction translates into a 13% reduction in the risk of coronary disease over 10 years, using the computer program for risk estimation provided with the new British guidelines. 3 A review of clinical trials with phytosterols found that the serum lipid response varies widely (reductions in the concentrations of low density lipoprotein cholesterol of 2-33%) depending on study design, amount of phytosterol intake, and initial cholesterol concentration. 4 When sitostanol was used with a low intake of fat (less than 30% of total energy intake) and cholesterol (less than 200 mg/day) it did not lower cholesterol concentration significantly. 5 The evidence therefore suggests that this margarine spread may reduce cholesterol concetntration in people consuming an average British diet, but in those following a healthy fat modified diet this costly product is unlikely further to reduce lipid concentrations.
Targeting BAFF/BLyS in lupus: is the glass half-full or half-empty?: Table 1
Authors: Frédéric A Houssiau, Andrea Doria
Journal: Annals of the Rheumatic Diseases (2015)

BAFF/BLyS, a pivotal cytokine in B-cell development, survival and proliferation,1 became a trusted target in systemic lupus erythematosus (SLE) more than 15 years ago when the growth factor was shown to be involved in the pathogenesis of both preclinical models and human SLE.2 ,3

Anti-BLyS monoclonal antibody belimumab (BEL) was licensed in 2011 for the treatment of SLE based on the results of the BLISS 52 and 76 phase III trials, which showed superiority compared with placebo, based on the percentage of patients achieving the SLE Responder Index 4 (SRI-4), a composite endpoint requiring (a) a reduction of ≥4 points in SELENA-SLEDAI score, (b) no new British Isles Lupus Assessment Group 2004 (BILAG) index score A or no more than 1 new BILAG B score and (c) no worsening (increase ≥0.3 points from baseline) in Physician's Global Assessment. At week 52, the delta efficacy between BEL and placebo (both on top of standard of care) was 14.0% and 9.7% in favour of the study drug in BLISS 52 and 76, respectively.4 ,5 …
Ongoing transmission of avian influenza A viruses in Hong Kong despite very comprehensive poultry control measures: A prospective seroepidemiology study
Authors: Kelvin K.W. To, Ivan F.N. Hung, Yin-Ming Lui, Florence K.Y. Mok, Andy S.F. Chan, Patrick T.W. Li, Tin-Lun Wong, Deborah T.Y. Ho, Jasper F.W. Chan, Kwok-Hung Chan, Kwok-Yung Yuen
Journal: Journal of Infection (2015)
Differentiating between health and respiratory disease using speech breathing pattern analysis
Authors: Rokhsaneh Tehrany, Anna Barney, Anne Bruton
Journal: European Respiratory Journal (2014)

Background:  While breathing patterns produced during speech have been reported to differ between healthy adults and patients with respiratory disease, it is not known whether the type of speech influences the detection of these differences.   Aim:  To compare speech breathing patterns between healthy adults and patients with chronic respiratory disease during a spontaneous speech task and an oral reading task.   Method:  Breathing patterns were recorded non-invasively using Respiratory Inductive Plethysmography (RIP) from 29 healthy adults (mean age 33.7 ± 12.64) and 20 patients (mean age 69.7 ± 8.81) with chronic respiratory disease during a spontaneous speech and oral reading task, each lasting two minutes. Offline analysis was performed using Matlab and six breathing parameters were extracted: Inspiration and expiration time (T I  and T E ), breathing cycle duration (Ttot), respiratory rate (RR) and inspiration and expiration volume (Iv and Ev).   Results:  A statistically significant difference ( p  I  ( p  = 0.02), T E  ( p  = 0.02), Ttot ( p  = 0.04), RR ( p  = 0.02), Iv ( p  = 0.00), Ev ( p  = 0.00)) during the spontaneous speech task. Statistically significant differences were found for two breathing parameters (Iv ( p  = 0.02) and Ev ( p  = 0.01)) during the reading task.   Conclusion:  These findings suggest that a spontaneous speech task is more useful than an oral reading task for differentiating between respiratory disease patients and healthy people. If confirmed in larger samples, this has implications for monitoring respiratory health using speech breathing patterns.
National Trends in the Use of Cardiac Resynchronization Therapy With or Without Implantable Cardioverter-Defibrillator
Authors: Charlotta Lindvall, Neal A. Chatterjee, Yuchiao Chang, Betty Chernack, Vicki A. Jackson, Jagmeet P. Singh, Joshua P. Metlay
Journal: Circulation (2015)

Candidates for cardiac resynchronization therapy (CRT) receive either a biventricular pacemaker or a biventricular pacemaker with an implantable cardioverter-defibrillator (CRT-D). Optimal device selection remains challenging because the benefit of implantable cardioverter-defibrillator therapy may not be uniform, particularly in patients at competing risk of nonsudden death.