tbuckley/cabot-search huggingface dataset:
Docetaxel plus oxaliplatin with or without fluorouracil or capecitabine in metastatic or locally recurrent gastric cancer: a randomized phase II study
Authors: E. Van Cutsem, C. Boni, J. Tabernero, B. Massuti, G. Middleton, F. Dane, P. Reichardt, F.L. Pimentel, A. Cohn, P. Follana, M. Clemens, A. Zaniboni, V. Moiseyenko, M. Harrison, D.A. Richards, H. Prenen, S. Pernot, E. Ecstein-Fraisse, S. Hitier, P. Rougier
Journal: Annals of Oncology (2014)
The cDNA cloning and molecular evolution of reptile and pigeon lactate dehydrogenase isozymes
Authors: H. Mannen, S. C. Tsoi, J. S. Krushkal, W. H. Li, S. S. Li
Journal: Molecular Biology and Evolution (1997)

The cDNAs encoding lactate dehydrogenase isozymes LDH-A (muscle) and LDH-B (heart) from alligator and turtle and LDH-A, LDH-B, and LDH-C (testis) from pigeon were cloned and sequenced. The evolutionary relationships among vertebrate LDH isozymes were analyzed. Contrary to the traditional belief that the turtle lineage branched off before the divergence between the lizard/alligator and bird lineages, the turtle lineage was found to be clustered with either the alligator lineage or the alligator-bird clade, while the lizard lineage was found to have branched off before the divergence between the alligator/turtle and bird lineages. The pigeon testicular LDH-C isozyme was evidently duplicated from LDH-B (heart), so it is not orthologous to the mammalian testicular LDH-C isozymes.
IL10 and PD-1 Cooperate to Limit the Activity of Tumor-Specific CD8+ T Cells
Authors: Zhaojun Sun, Julien Fourcade, Ornella Pagliano, Joe-Marc Chauvin, Cindy Sander, John M. Kirkwood, Hassane M. Zarour
Journal: Cancer Research (2015)

Abstract Immune checkpoint inhibitors show great promise as therapy for advanced melanoma, heightening the need to determine the most effective use of these agents. Here, we report that programmed death-1high (PD-1high) tumor antigen (TA)–specific CD8+ T cells present at periphery and at tumor sites in patients with advanced melanoma upregulate IL10 receptor (IL10R) expression. Multiple subsets of peripheral blood mononucleocytes from melanoma patients produce IL10, which acts directly on IL10R+ TA-specific CD8+ T cells to limit their proliferation and survival. PD-1 blockade augments expression of IL10R by TA-specific CD8+ T cells, thereby increasing their sensitivity to the immunosuppressive effects of endogenous IL10. Conversely, IL10 blockade strengthened the effects of PD-1 blockade in expanding TA-specific CD8+ T cells and reinforcing their function. Collectively, our findings offer a rationale to block both IL10 and PD-1 to strengthen the counteraction of T-cell immunosuppression and to enhance the activity of TA-specific CD8+ T cell in advanced melanoma patients. Cancer Res; 75(8); 1635–44. ©2015 AACR.
Issues for DSM-5: Whither Melancholia? The Case for Its Classification as a Distinct Mood Disorder
Authors: Gordon Parker, Max Fink, Edward Shorter, Michael Alan Taylor, Hagop Akiskal, German Berrios, Tom Bolwig, Walter A. Brown, Bernard Carroll, David Healy, Donald F. Klein, Athanasios Koukopoulos, Robert Michels, Joel Paris, Robert T. Rubin, Robert Spitzer, Conrad Swartz
Journal: American Journal of Psychiatry (2010)

Melancholia, a syndrome with a long history and distinctly specific psychopathological features, is inadequately differentiated from major depression by the DSM-IV specifier.It is neglected in clinical assessment (e.g., in STAR*D [1]) and treatment selection (e.g., in the Texas Medication Algorithm Project [2]).Nevertheless, it possesses a distinctive biological homogeneity in clinical experience and laboratory test markers, and it is differentially responsive to specific treatment interventions.It therefore deserves recognition as a separate identifiable mood disorder.Melancholia has been variously described as "endogenous," "endogenomorphic," "autonomous," "type A," "psychotic," and "typical" depression (3-6).In contrast to the current DSM criteria for the melancholia specifier (features of which are often shared with major depression), it has characteristic clinical features (5-7).
Neurohumoral Features of Myocardial Stunning Due to Sudden Emotional Stress
Authors: Ilan S. Wittstein, David R. Thiemann, Joao A.C. Lima, Kenneth L. Baughman, Steven P. Schulman, Gary Gerstenblith, Katherine C. Wu, Jeffrey J. Rade, Trinity J. Bivalacqua, Hunter C. Champion
Journal: New England Journal of Medicine (2005)

Reversible left ventricular dysfunction precipitated by emotional stress has been reported, but the mechanism remains unknown.
Health Effects of Arsenic and Chromium in Drinking Water: Recent Human Findings
Authors: Allan H. Smith, Craig M. Steinmaus
Journal: Annual Review of Public Health (2008)

Even at high concentrations, arsenic-contaminated water is translucent, tasteless, and odorless. Yet almost every day, studies report a continually increasing plethora of toxic effects that have manifested in exposed populations throughout the world. In this article we focus on recent findings, in particular those associated with major contributions since 2006. Early life exposure, both in utero and in childhood, has been receiving increased attention, and remarkable increases in consequent mortality in young adults have been reported. New studies address the dose-response relationship between drinking-water arsenic concentrations and skin lesions, and new findings have emerged concerning arsenic and cardiovascular disease. We also review the increasing epidemiological evidence that the first step of methylation of inorganic arsenic to monomethylated arsenic (MMA) is actually an activation step rather than the first step in detoxification, as once thought. Hexavalent chromium differs from arsenic in that it discolors water, turning the water yellow at high concentrations. A controversial issue is whether chromium causes cancer when ingested. A recent publication supports the original findings in China of increased cancer mortality in a population where well water turned yellow with chromium.
On-line computation of cardiac output with the thermodilution method, using a digital minicomputer
Authors: L. H. SNOECKX, J. L. VERHEYEN, A. V. D. WATER, P. LEWI, R. S. RENEMAN
Journal: Cardiovascular Research (1976)

In the present study, several techniques for calculating cardiac output were evaluated in order to find an accurate technique suitable for on-line digital computation. The thermodilution method was evaluated by different calculation techniques and by comparing these techniques with electromagnetic flowmeter values. Comparison of thermal dilution curves, manually calculated by the log-normal and the exponential assumption, showed a correlation coefficient of 0.978 between the two methods, the former values being 11% higher. The exponential method correlated very well with the technique, using a correction factor for injection errors (r = 0.999). Since the exponential technique correlated well with the electromagnetic values (r = 0.84) and since it was less complicated than the technique, using correction factors, this technique was chosen for automation. Comparison of exponential calculated thermodilution values with a digital computer and manually, showed a correlation coefficient of 0.991. Therefore, it was concluded that on-line computation of thermodilution curves improves the applicability of the thermodilution techniques as a means of measuring cardiac output.
Comparison of the sensitivity and specificity of two whole blood interferon-gamma assays for M. tuberculosis infection
Authors: Nobuyuki Harada, Kazue Higuchi, Takashi Yoshiyama, Yoshiko Kawabe, Akira Fujita, Yuka Sasaki, Masahide Horiba, Satoshi Mitarai, Makoto Yonemaru, Hideo Ogata, Haruhiko Ariga, Atsuyuki Kurashima, Akihiko Wada, Mikio Takamori, Fumio Yamagishi, Kiminori Suzuki, Toru Mori, Nobukatsu Ishikawa
Journal: Journal of Infection (2008)
An assessment of physicians knowledge of the GINA guidelines
Authors: Victor Umoh, Effiong Akpan, Anthony Aluka, Datonye Alasia, John Ekott
Journal: European Respiratory Journal (2011)

Introduction: The Global Strategy for Asthma Management and Prevention (GINA) is useful in the management of asthma patients.

Aims and objectives: We hypothesized that many physicians who attend to asthma patients are not familiar with the components of the GINA guidelines.

Methods: Based on the GINA guidelines, a multiple choice questionnaire which addressed various components of the guidelines was distributed to physicians who attend to asthma patients.

Results: 54 Physicians were randomly selected from among 118 physicians from 2 Teaching Hospitals in Nigeria: 31 from Internal medicine, 20 from Family Medicine and 3 from Respiratory unit. There were 10 general internists, 2 medical officers, 28 junior residents, 11 senior residents and 3 consultants. 72.2% of the respondents did not attend any Continued Medical Education (CME) in asthma after graduation. Those of them who attended a CME post graduation scored higher than those who had not attended but this was not significant (39.78% Vs 31.2%) There was also an improvement in total performance with hierarchy but this was not statistically significant. Respiratory physicians scored significantly higher than the Internal medicine and the Family physicians (70.96% Vs 34.13% Vs 37.09%). The knowledge of pathological basis of asthma had the highest sub-score (50%) followed by diagnosis (48.7%) with asthma education having the least score (16.6%). Overall the average total score was poor (37.2%).

Conclusion: By identifying the areas of deficiency in each group of Doctors we can design education intervention programmes to improve the understanding of the GINA guidelines among physicians and ultimately the quality of care.
Macrophage Stimulating Protein May Promote Tubular Regeneration after Acute Injury
Authors: Vincenzo Cantaluppi, Luigi Biancone, Giuseppe Mauriello Romanazzi, Federico Figliolini, Silvia Beltramo, Francesco Galimi, Maria Gavina Camboni, Elisa Deriu, Piergiulio Conaldi, Antonella Bottelli, Viviana Orlandi, Maria Beatriz Herrera, Alfonso Pacitti, Giuseppe Paolo Segoloni, Giovanni Camussi
Journal: Journal of the American Society of Nephrology (2008)

Macrophage-stimulating protein (MSP) exerts proliferative and antiapoptotic effects, suggesting that it may play a role in tubular regeneration after acute kidney injury. In this study, elevated plasma levels of MSP were found both in critically ill patients with acute renal failure and in recipients of renal allografts during the first week after transplantation. In addition, MSP and its receptor, RON, were markedly upregulated in the regenerative phase after glycerol-induced tubular injury in mice. In vitro, MSP stimulated tubular epithelial cell proliferation and conferred resistance to cisplatin-induced apoptosis by inhibiting caspase activation and modulating Fas, mitochondrial proteins, Akt, and extracellular signal-regulated kinase. MSP also enhanced migration, scattering, branching morphogenesis, tubulogenesis, and mesenchymal de-differentiation of surviving tubular cells. In addition, MSP induced an embryonic phenotype characterized by Pax-2 expression. In conclusion, MSP is upregulated during the regeneration of injured tubular cells, and it exerts multiple biologic effects that may aid recovery from acute kidney injury.
Regulation of cell cycle transition and induction of apoptosis in HL-60 leukemia cells by lipoic acid: role in cancer prevention and therapy
Authors: Elangovan Selvakumar, Tze-chen Hsieh
Journal: Journal of Hematology & Oncology (2008)

Lipoic acid (LA), a potent antioxidant, has been used as a dietary supplement to prevent and treat many diseases, including stroke, diabetes, neurodegenerative and hepatic disorders. Recently, potent anti-tumorigenic effects induced by LA were also reported and evident as assayed by suppression of cell proliferation and induction of apoptosis in malignant cells. However, the mechanism by which LA elicits its chemopreventive effects remains unclear.Herein, we investigated whether LA elicits its anti-tumor effects by inducing cell cycle arrest and cell death in human promyelocytic HL-60 cells. The results showed that LA inhibits both cell growth and viability in a time- and dose-dependent manner. Disruption of the G1/S and G2/M phases of cell cycle progression accompanied by the induction of apoptosis was also observed following LA treatment. Cell cycle arrest by LA was correlated with dose-dependent down regulation of Rb phosphorylation, likely via suppression of E2F-dependent cell cycle progression with an accompanying inhibition of cyclin E/cdk2 and cyclin B1/cdk1 levels. Evidence supporting the induction of apoptosis by LA was based on the appearance of sub-G1 peak in flow cytometry analysis and the cleavage of poly(ADP-ribose) polymerase (PARP) from its native 112-kDa form to the 89-kDa truncated product in immunoblot assays. Apoptosis elicited by LA was preceded by diminution in the expression of anti-apoptotic protein bcl-2 and increased expression of apoptogenic protein bax, and also the release and translocation of apoptosis inducing factor AIF and cytochrome c from the mitochondria to the nucleus, without altering the subcellular distribution of the caspases.This study provides evidence that LA induces multiple cell cycle checkpoint arrest and caspase-independent cell death in HL-60 cells, in support of its efficacious potential as a chemopreventive agent.
Reduction of granulocyte activation during hemodialysis with regional citrate anticoagulation
Authors: J Böhler, P Schollmeyer, B Dressel, G Dobos, W H Hörl
Journal: Journal of the American Society of Nephrology (1996)

Neutropenia and degranulation of neutrophils during hemodialysis with cellulosic membranes have been linked to complement activation, whereas in the synthetic polymethyl methacrylate (PMMA) membrane, degranulation occurs without notable complement activation. The mechanisms of neutrophil degranulation under these conditions have not yet been elucidated. Ionized calcium is an important prerequisite of granulocyte activation during in vitro blood contact with both types of artificial surfaces. This study compared the effect of normal ionized calcium during heparin anticoagulation with the effect of extracorporeal calcium depletion during regional citrate anticoagulation on activation of blood components. Because ionized calcium is reduced only in the extra-corporeal circuit, citrate anticoagulation in addition helps to differentiate between extracorporeal and systemic activation phenomena. Twelve chronic hemodialysis patients were dialyzed with polymethyl methacrylate (PMMA, 16 treatments) or cuprophane (CUP, 16 treatments) membranes either during regional citrate anticoagulation or while anticoagulated with heparin. During hemodialysis with CUP, anticoagulation with citrate significantly reduced neutropenia, C3a levels, and lactoferrin release. Elastase concentrations, however, were not reduced by citrate, probably because elastase release occurred not locally in the cuprophane dialyzer, but mostly in the systemic circulation of the patient. PMMA did not elevate C3a levels, and neutropenia was only mild. Both parameters were not influenced by citrate anti-coagulation. However, PMMA profoundly induced elastase and lactoferrin release during heparin anti-coagulation. Depletion of ionized calcium markedly reduced PMMA-mediated neutrophil degranulation in the extracorporeal circuit. The results indicate that ionized calcium is a requirement for neutrophil degranulation during hemodialysis. In PMMA membranes, neutrophil degranulation occurs independent of high complement levels, occurs at least partially inside the dialyzer, and requires the presence of ionized calcium in the extracorporeal circuit. In cuprophane membranes, degranulation was uncoupled from neutropenia and did not correlate with the degree of complement activation. Even in cuprophane dialysis, degranulation of secondary granules was markedly dependent on ionized calcium levels in the extracorporeal circuit.
Selenoprotein Gene Variants, Toenail Selenium Levels, and Risk for Advanced Prostate Cancer
Authors: Milan S. Geybels, Piet A. van den Brandt, Leo J. Schouten, Frederik J. van Schooten, Simone G. van Breda, Margaret P. Rayman, Fiona R. Green, Bas A. J. Verhage
Journal: JNCI Journal of the National Cancer Institute (2014)

Lower selenium levels have been associated with increased risk of prostate cancer (PCa), and genetic variation in the selenoprotein genes selenoprotein P (SEPP1) and glutathione peroxidase 1 (GPX1) is thought to modify this relationship. We investigated whether the association between toenail selenium levels and advanced PCa risk in the prospective Netherlands Cohort Study is modified by common genetic variation in SEPP1 and GPX1. Toenail clippings were used to determine selenium levels and to isolate DNA for genotyping. This case–cohort study, which included 817 case subjects with advanced PCa and 1048 subcohort members, was analyzed with Cox regression models. All statistical tests were two-sided. Three genetic variants were associated with advanced (stage III/IV or IV) PCa risk: SEPP1 rs7579 (lower risk; Ptrend = .01), GPX1 rs17650792 (higher risk; Ptrend = .03), and GPX1 rs1800668 (lower risk; Ptrend = .005). Toenail selenium levels were inversely associated with advanced PCa risk, independently of common genetic variation in SEPP1 and GPX1.
A mindfulness-based group intervention to reduce psychological distress and fatigue in patients with inflammatory rheumatic joint diseases: a randomised controlled trial
Authors: Heidi A Zangi, Petter Mowinckel, Arnstein Finset, Liv R Eriksson, Turid Ø Høystad, Anne Kristine Lunde, Kåre B Hagen
Journal: Annals of the Rheumatic Diseases (2011)

<h3>Objective</h3> To evaluate the effects of a mindfulness-based group intervention, the Vitality Training Programme (VTP), in adults with inflammatory rheumatic joint diseases. <h3>Methods</h3> In a randomised controlled trial, the VTP—a 10-session mindfulness-based group intervention including a booster session after 6 months—was compared with a control group that received routine care plus a CD for voluntary use with mindfulness-based home exercises. The primary outcome was psychological distress measured by the General Health Questionnaire-20. Self-efficacy (pain and symptoms) and emotion-focused coping (emotional processing and expression) were used as co-primary outcomes. Secondary outcomes included pain, fatigue, patient global disease activity, self-care ability and well-being. Effects were estimated by mixed models repeated measures post-intervention and at 12-month follow-up. <h3>Results</h3> Of 73 participants randomised, 68 completed assessments post-intervention and 67 at 12 months. Significant treatment effects in favour of the VTP group were found post-treatment and maintained at 12 months in psychological distress (adjusted mean between-group difference −3.7, 95% CI −6.3 to −1.1), self-efficacy pain (9.1, 95% CI 3.4 to 14.8) and symptoms (13.1, 95% CI 6.7 to 19.3), emotional processing (0.3, 95% CI 0.02 to 0.5), fatigue (−1.1, 95% CI −1.8 to −0.4), self-care ability (1.0, 95% CI 0.5 to 1.6) and overall well-being (0.6, 95% CI 0.1 to 1.2). No significant group differences were found in emotional expression, pain or disease activity. <h3>Conclusion</h3> The VTP improved most primary and secondary outcomes compared with individual use of CD exercises. Improvements were maintained at 12 months, suggesting that the VTP is a beneficial complement to existing treatments for patients with inflammatory rheumatic joint diseases.
Predicting bone loss following orthotopic liver transplantation
Authors: O M Crosbie, R Freaney, M J McKenna, M P Curry, J E Hegarty
Journal: Gut (1999)

BACKGROUND Hepatic osteodystrophy occurs in the majority of patients with advanced chronic liver disease with the abnormalities in bone metabolism accelerating following orthotopic liver transplantation (OLT). AIMS To examine changes in bone mineral density (BMD) following OLT and to investigate factors that lead to bone loss. METHODS Twelve patients had BMD (at both the lumbar spine (LS) and femoral neck (FN)) and biochemical markers measured preoperatively and for 24 months following OLT. RESULTS BMD was low in 75% of patients prior to OLT and decreased significantly from baseline at the LS at three months and the FN at six months. BMD began to increase thereafter at both sites, approaching baseline values at the LS by 12 months. Bone formation markers, osteocalcin and procollagen type I carboxy propeptide, decreased immediately post-OLT, with a concomitant increase seen in the resorption markers pyridinoline and deoxypyridinoline. This resulted in a negative uncoupling index early post-OLT, that rebounded to positive values after six months. There was a significant correlation between the change in the uncoupling index between six and three months which preceded the increase in BMD at 12 months. The decrease in BMD recorded early post-OLT correlated with vitamin D levels at three months. CONCLUSIONS Results suggest that increased resorption and inadequate formation are the major contributors to additional bone loss following OLT. Non-invasive biochemical markers precede later changes in BMD in this patient group following OLT and may have a role in investigating and planning intervention strategies to prevent bone loss in future studies.
Elevated Transferrin Saturation and Risk of Diabetes
Authors: Christina Ellervik, Thomas Mandrup-Poulsen, Henrik Ullits Andersen, Anne Tybjærg-Hansen, Merete Frandsen, Henrik Birgens, Børge G. Nordestgaard
Journal: Diabetes Care (2011)

We tested the hypothesis that elevated transferrin saturation is associated with an increased risk of any form of diabetes, as well as type 1 or type 2 diabetes separately.We used two general population studies, The Copenhagen City Heart Study (CCHS, N = 9,121) and The Copenhagen General Population Study (CGPS, N = 24,195), as well as a 1:1 age- and sex-matched population-based case-control study with 6,129 patients with diabetes from the Steno Diabetes Centre and 6,129 control subjects, totaling 8,535 patients with diabetes and 37,039 control subjects.In the combined studies, odds ratios in those with transferrin saturation ≥50% vs. <50% were 2.1 (95% CI 1.3-3.4; P = 0.003) for any form of diabetes; 2.6 (1.2-5.6; P = 0.01) for type 1 diabetes; and 1.7 (1.4-2.1; P = 0.001) for type 2 diabetes.Elevated transferrin saturation confers a two- to threefold increased risk of developing any form of diabetes, as well as type 1 and type 2 diabetes separately.
Recommendations of the National Heart, Lung, and Blood Institute Working Group on Future Direction in Cardiac Surgery
Authors: William A. Baumgartner, Stephanie Burrows, Pedro J. del Nido, Timothy J. Gardner, Suzanne Goldberg, Robert C. Gorman, George V. Letsou, Alice Mascette, Robert E. Michler, John D. Puskas, Eric A. Rose, Todd K. Rosengart, Frank W. Sellke, Sara J. Shumway, Norbert Wilke
Journal: Circulation (2005)

New surgical procedures, imaging modalities, and medical devices have improved therapy for many patients and made treatment possible for others who have had few options in the past. In February 2004, the National Heart, Lung, and Blood Institute's (NHLBI) Advisory Council proposed that the institute evaluate the status and future directions in cardiac surgery. In response to this recommendation, the NHLBI convened a working group of cardiac surgeons on May 7 and 8, 2004, to assess the state of cardiac surgery research, identify critical gaps in current knowledge, determine areas of opportunity, and obtain specific recommendations for future research activities. The working group discussed surgical revascularization, novel surgical approaches, valvular research directions, biotechnology and cell-based therapy, heart failure, imaging modalities, and barriers to clinical research and presents its recommendations here.