tbuckley/cabot-search huggingface dataset:
Genetic Predictors of Response to Serotonergic and Noradrenergic Antidepressants in Major Depressive Disorder: A Genome-Wide Analysis of Individual-Level Data and a Meta-Analysis
Authors: Katherine E. Tansey, Michel Guipponi, Nader Perroud, Guido Bondolfi, Enrico Domenici, David Evans, Stephanie K. Hall, Joanna Hauser, Neven Henigsberg, Xiaolan Hu, Borut Jerman, Wolfgang Maier, Ole Mors, Michael O'Donovan, Tim J. Peters, Anna Placentino, Marcella Rietschel, Daniel Souery, Katherine J. Aitchison, Ian Craig, Anne Farmer, Jens R. Wendland, Alain Malafosse, Peter Holmans, Glyn Lewis, Cathryn M. Lewis, Tine Bryan Stensbøl, Shitij Kapur, Peter McGuffin, Rudolf Uher
Journal: PLoS Medicine (2012)

Testing whether genetic information could inform the selection of the best drug for patients with depression, Rudolf Uher and colleagues searched for genetic variants that could predict clinically meaningful responses to two major groups of antidepressants.
Coding and Transformations in the Olfactory System
Authors: Naoshige Uchida, Cindy Poo, Rafi Haddad
Journal: Annual Review of Neuroscience (2014)

How is sensory information represented in the brain? A long-standing debate in neural coding is whether and how timing of spikes conveys information to downstream neurons. Although we know that neurons in the olfactory bulb (OB) exhibit rich temporal dynamics, the functional relevance of temporal coding remains hotly debated. Recent recording experiments in awake behaving animals have elucidated highly organized temporal structures of activity in the OB. In addition, the analysis of neural circuits in the piriform cortex (PC) demonstrated the importance of not only OB afferent inputs but also intrinsic PC neural circuits in shaping odor responses. Furthermore, new experiments involving stimulation of the OB with specific temporal patterns allowed for testing the relevance of temporal codes. Together, these studies suggest that the relative timing of neuronal activity in the OB conveys odor information and that neural circuits in the PC possess various mechanisms to decode temporal patterns of OB input.
New approaches under development: cardiovascular embryology applied to heart disease
Authors: Karl Degenhardt, Manvendra K. Singh, Jonathan A. Epstein
Journal: Journal of Clinical Investigation (2013)

Despite many innovative advances in cardiology over the past 50 years, heart disease remains a major killer. The steady progress that continues to be made in diagnostics and therapeutics is offset by the cardiovascular consequences of the growing epidemics of obesity and diabetes. Truly innovative approaches on the horizon have been greatly influenced by new insights in cardiovascular development. In particular, research in stem cell biology, the cardiomyocyte lineage, and the interactions of the myocardium and epicardium have opened the door to new approaches for healing the injured heart.
Ultrafine particles in urban air and respiratory health among adult asthmatics
Authors: P. Penttinen, K.L. Timonen, P. Tiittanen, A. Mirme, J. Ruuskanen, J. Pekkanen
Journal: European Respiratory Journal (2001)

Airborne particles are associated with adverse health effects and contribute to excess mortality in epidemiological studies. A recent hypothesis proposes that the high numbers of ultrafine (&lt;0.1 μm diameter) particles in ambient air might provoke alveolar inflammation and subsequently cause exacerbations in pre-existing cardiopulmonary diseases. To test the hypothesis adult asthmatics were followed with daily peak expiratory flow (PEF) measurements and symptom and medication diaries for six months, while simultaneously monitoring particulate pollution in ambient air. The associations between daily health endpoints of 57 asthmatics and indicators of air pollution were examined by multivariate regression models. Daily mean number concentration of particles, but not particle mass (PM 10 (particle mass &lt;10 μm), PM 2.5–10 , PM 2.5 , PM 1 ), was negatively associated with daily PEF deviations. The strongest effects were seen for particles in the ultrafine range. However, the effect of ultrafine particles could not definitely be separated from other traffic generated pollutants, namely nitric oxide, nitrogen dioxide and carbon monoxide. No associations were observed with respiratory symptoms or medication use. Particle mass measurements can be strongly influenced by mechanically produced, soil-derived particles, which may not be associated with adverse health effects. Therefore, air quality monitoring should include particle number concentrations, which mainly reflect ultrafine particles.
Nature and biological significance of free radicals generated during bicarbonate hemodialysis.
Authors: M M Epperlein, J Nourooz-Zadeh, S D Jayasena, J S Hothersall, A Noronha-Dutra, G H Neild
Journal: Journal of the American Society of Nephrology (1998)

This study investigates evidence of oxidative stress during bicarbonate hemodialysis by measuring total glutathione and lipid peroxidation products in plasma, and characterizes the free radicals produced by neutrophils from healthy volunteers when incubated in vitro with increasing concentrations of bicarbonate. Blood samples were taken from nine hemodialysis patients before and after two hemodialysis sessions. Plasma hydroperoxides and total glutathione were measured. A significant increase was found in total glutathione (1.04 +/- 0.4 versus 2.11 +/- 0.9 microM, P < 0.001) and hydroperoxides by ferrous oxidation in xylenol orange version 2 method (4.6 +/- 0.53 versus 6.4 +/- 0.63 microM, P < 0.001) after hemodialysis, which indicated increased oxidative injury during hemodialysis. Normal neutrophils, activated by contact adhesion, produced a dose-dependent increase in free radical production (measured by luminol-enhanced chemiluminescence) when incubated with increasing concentrations of bicarbonate (up to 35 mM). Bicarbonate had the same effect on the chemiluminescence of a cell-free hypoxanthine/acetaldehyde system generating superoxide, but not on a glucose oxidase/myeloperoxidase system generating hydrogen peroxide and hypochlorous acid. These findings are consistent with (1) the hypothesis that superoxide generated during hemodialysis reacts with bicarbonate to form the toxic carbonate and formate radicals and (2) our previous observation that some patients undergoing bicarbonate (but not lactate) dialysis have increased plasma concentrations of formate after hemodialysis. It is suggested that the increased plasma total glutathione and hydroperoxide concentrations are a result of lipid peroxidation by these species. These reactive radicals can initiate lipid peroxidation and contribute to the cardiovascular complications of hemodialysis patients.
Hemodynamic resistance as a measure of functional impairment in aortic valvular stenosis.
Authors: L E Ford, T Feldman, Y C Chiu, J D Carroll
Journal: Circulation Research (1990)

Calculated valve area depicts anatomical stenosis but does not quantify hemodynamic impairment. We propose that hemodynamic resistance, defined as the mean pressure gradient across the valve divided by mean flow rate during systolic ejection, gives a better indication of hemodynamic obstruction. This index was compared with Gorlin valve area in 40 patients with aortic stenosis. Calculated area ranged from 0.22 to 1.26 cm2, and mean transvalvular resistance ranged from 117 to 1,244 dyne.sec.cm-5. In general, resistance varied inversely with calculated area, but there was substantial variation about the mean relation. All of the variation could be accounted for by variations in the pressure gradients at each value of calculated area. Resistance was higher in proportion to area when flow and pressure gradient were high. Analysis of five published studies of a total of 83 valves showed that calculated area changed at least three times more than resistance when pressure gradient was varied. The utility of resistance as an index of stenosis is demonstrated by example calculations that show how during exercise a stenotic valve increases the ventricular work rate out of proportion to the work done on the peripheral resistance. These calculations are possible because hemodynamic resistance defines functional impairment in units commonly used for quantification of opposition to flow. Furthermore, resistance appears to be less dependent than area on conditions of measurement and does not require an empirical constant.
Characteristics of patients with rheumatoid arthritis in France: a study of 1109 patients managed by hospital based rheumatologists
Authors: J Sany, P Bourgeois, A Saraux, S Durieux, A Lafuma, J P Daurès, F Guillemin, J Sibilia
Journal: Annals of the Rheumatic Diseases (2004)

To describe the characteristics of rheumatoid arthritis in patients managed by hospital based rheumatologists in France.All public and non-profit private hospitals in France were invited to participate in a cross sectional study. Clinical data on the day of inclusion and health resources used for rheumatoid arthritis over the previous 12 months (treatments, medical devices, physician visits, examinations, hospital admissions, and other health professional care) were recorded.1109 patients from 75 centres located throughout the country were included (846 female; mean disease duration, 10.6 years; mean age, 56.7 years). Active disease (swollen joint count > or =6, tender joint count > or =6, and two of: morning stiffness > or =45 min, C reactive protein > or =20 mg/l, erythrocyte sedimentation rate >28 mm/h) was observed in 146 patients (13.2%). Mean (SD) DAS(28) was 4.51 (1.55). Severe extra-articular manifestations were reported in 8.4%. ACR functional status was: class I, 19%; class II, 28%; class III, 31%; class IV, 22%. Comorbidity was observed in 44.9% of cases, particularly chronic pulmonary disease and coronary or peripheral vascular disease. Average AIMS2-SF dimension scores were between 4.56 and 6.18, and mean HAQ was 1.32 (0.77). Disease modifying antirheumatic drugs (DMARDs) were prescribed for 82.1% of the patients. During the previous four weeks, one DMARD was used in 62.5%, and two or more in 19.5%. Corticosteroids were prescribed in 72%.In a rheumatoid arthritis population managed by hospital based rheumatologists, the disease was active in 13% and severe in more than one third of cases.
When Right May Not Be Right
Authors: Karoly Kaszala, Kenneth A. Ellenbogen
Journal: Circulation (2010)

C ardiac resynchronization therapy (CRT) in appropriately selected patients has been shown to improve cardiac function, heart failure symptoms, and survival. 1,2On the basis of results of large, randomized trials, current American Heart Association/American College of Cardiology/Heart Rhythm Society guidelines recommend consideration of CRT in patients with cardiomyopathy on optimal medical therapy with left ventricular ejection fraction Ͻ35%, New York Heart Association class III or IV symptoms, and QRS duration Ͼ120 ms. 3 The idea of resynchronization therapy was derived from the seminal observations that intraventricular conduction abnormalities, extensively characterized in patients with left bundle-branch block (LBBB), adversely affect left ventricular mechanics.LBBB produces predictable changes in the left ventricular activation sequence. 4,5Abnormal activation of the interventricular septum and markedly delayed activation of the lateral left ventricle are typically seen in patients with LBBB.However, left ventricular activation patterns may be highly variable and more complex in patients with underlying cardiomyopathy. 6Delayed, dyssynchronous electromechanical activation in these segments leads to increased cardiac work, less efficient cardiac contraction, and lower cardiac output. 7Electric (and mechanical) preactivation of the late-activating left ventricular region with CRT has been accepted to be prerequisite for successful clinical response. 8Although remarkable symptomatic improvement is seen in many patients, up to 30% of subjects who participated in CRT trials failed to respond to therapy or may have worsened. 2Several clinical features have been identified that carry adverse clinical prognosis and predict less response to CRT therapy (Table ).Despite extensive efforts, preimplant identification of nonresponders remains a significant problem and erodes the overall clinical (and cost) effectiveness of CRT therapy.
Comparison of hirudin and heparin as adjuncts to streptokinase thrombolysis in a canine model of coronary thrombosis.
Authors: D F Rigel, R W Olson, R W Lappe
Journal: Circulation Research (1993)

Recombinant desulfatohirudin (HI), a potent and specific thrombin inhibitor, was compared with heparin (HE) as an adjunct to streptokinase thrombolysis. In pentobarbital-anesthetized dogs, an occlusive thrombus (whole blood+thrombin) was introduced into the left anterior descending coronary artery (LAD) with superimposed endothelial damage and distal high-grade stenosis. Intravenous infusion of saline (vehicle), HI (0.3 mg/kg followed by 0.3 mg/kg per hour, 1 mg/kg followed by 1 mg/kg per hour, or 2 mg/kg followed by 2 mg/kg per hour), or HE (60 units/kg followed by 40 units/kg per hour or 100 units/kg followed by 60 units/kg per hour) was initiated 15 minutes before streptokinase (750,000 units for 60 minutes) administration. Vessel patency was monitored for 180 minutes after streptokinase administration with a volume flow probe on the proximal LAD. In dogs treated with no adjunctive agent (saline control), none of the vessels were recanalized with streptokinase. Both HI and HE promoted reperfusion, inhibited reocclusion, and reduced the residual thrombus mass in a dose-dependent fashion. However, at comparable levels of therapeutic anticoagulation (activated partial thromboplastin time [APTT] = 1.5-2.0 times baseline) HI exhibited a higher incidence of reperfusion (eight of eight dogs [100%] versus one of eight dogs [12%]), a shorter time to reperfusion (33 +/- 6 versus 59 minutes), a longer duration of initial reperfusion (106 +/- 21 versus 10 minutes), and a smaller residual thrombus mass than did HE. Likewise, the slope of the relation between the APTT prolongation and the total reperfusion time ("anticoagulation/antithrombosis profile") was almost five times higher for the combined HI data than for the HE data. Our results indicate that HI is more effective than HE in enhancing and sustaining coronary recanalization with streptokinase at a HI dose that modestly prolongs coagulation time and does not alter bleeding times.
Molecular Staging in Stage II and III Melanoma Patients and Its Effect on Long-Term Survival
Authors: Christiane Voit, Martina Kron, Juergen Rademaker, Markus Schwürzer-Voit, Wolfram Sterry, Lutz Weber, Cueneyt Özdemir, Thomas Proebstle, Ulrich Keilholz
Journal: Journal of Clinical Oncology (2005)

Purpose To assess the prognostic value of serial reverse transcriptase polymerase chain reaction (RT-PCR) -based measurements of tyrosinase mRNA in peripheral blood of stage II and III melanoma patients. Patients and Methods During routine follow-up of American Joint Committee on Cancer stage II and III melanoma patients, serial testing for tyrosinase transcripts in peripheral blood was performed by RT-PCR. The PCR results were compared with the clinical data collected during the follow-up. Results Over a period of 3 years, 111 patients (78 stage II and 33 stage III patients) were enrolled, and tyrosinase determinations were carried out. The 6-year disease-specific survival probability was 97% for patients always showing negative RT-PCR results and 67% for patients who tested positive at least once. In a Cox proportional hazards model, the prognostic value of sex, age, site of primary tumor, histologic subtype, stage, Breslow's tumor thickness, Clark level, and the time-dependent variable PCR result was assessed. Patients with a positive RT-PCR test had a distinctly higher risk of dying from melanoma, with a hazard ratio of 12.6 (95% CI, 3.4 to 46.3; P &lt; .001). Conclusion Our study shows a strong association between PCR and disease-specific survival time. Detection of tyrosinase mRNA in peripheral blood may be of similar importance for the clinical course of melanoma as the detection of micrometastatic disease in the sentinel lymph node. Whether a combination of these two factors leads to a better definition of the prognosis of melanoma patients is under investigation in current studies.
Bone marrow histology in marginal zone B-cell lymphomas: correlation with clinical parameters and flow cytometry in 120 patients
Authors: E. Boveri, L. Arcaini, M. Merli, F. Passamonti, S. Rizzi, L. Vanelli, E. Rumi, S. Rattotti, M. Lucioni, C. Picone, A. Castello, C. Pascutto, U. Magrini, M. Lazzarino, M. Paulli
Journal: Annals of Oncology (2008)
Dr Lazarus Explains
Authors: B. A. St. Andrews
Journal: JAMA (2000)

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Cytokine-induced meningitis is dramatically attenuated in mice deficient in endothelial selectins.
Authors: T Tang, P S Frenette, R O Hynes, D D Wagner, T N Mayadas
Journal: Journal of Clinical Investigation (1996)

Leukocyte accumulation in cerebrospinal fluid and disruption of the blood-brain barrier are central components of meningitis and are associated with a poor prognosis. Genetically engineered deficiencies or functional inhibition of endothelial leukocyte adhesion receptors P-, or P- plus E-selectins, lead to deficits in leukocyte rolling and extravasation. However, their impact on meningeal inflammation has not been tested previously. An acute cytokine-induced meningitis model associated with significant cerebrospinal fluid leukocyte accumulation (averaging 14,000 leukocytes/microl as early as 4 h) and blood-brain barrier permeability was developed in adult mice. This model was applied to mice deficient in P-selectin and mice doubly deficient in P- and E-selectins. Partial inhibition of cerebrospinal fluid leukocyte influx and permeability was noted in P-selectin-deficient mice. Mice doubly deficient in P- and E-selectins displayed a near complete inhibition of these parameters. Our results suggest that P- and E-selectins cooperatively contribute to meningitis and that functional blocking of both endothelial selectins in conjunction with antibiotics may provide a therapeutic approach for treatment of bacterial meningitis.
Postoperative Radiation Therapy for Endometrial Cancer: American Society of Clinical Oncology Clinical Practice Guideline Endorsement of the American Society for Radiation Oncology Evidence-Based Guideline
Authors: Larissa A. Meyer, Kari Bohlke, Matthew A. Powell, Amanda N. Fader, Gregg E. Franklin, Larissa J. Lee, Daniela Matei, Lourie Coallier, Alexi A. Wright
Journal: Journal of Clinical Oncology (2015)

Purpose To provide guidance on the role of adjuvant radiation therapy in the treatment of endometrial cancer. Methods “The Role of Postoperative Radiation Therapy for Endometrial Cancer: An ASTRO Evidence-Based Guideline” by Klopp et al, published in 2014 in Practical Radiation Oncology, was reviewed for developmental rigor by methodologists. The American Society for Radiation Oncology (ASTRO) guideline content and recommendations were further reviewed by the American Society of Clinical Oncology (ASCO) Endorsement Panel. Results The ASCO Endorsement Panel determined that the recommendations from the ASTRO guideline are clear, thorough, and based on the most relevant scientific evidence. ASCO endorsed the ASTRO guideline with several qualifying statements. Recommendations Surveillance without adjuvant radiation therapy is a reasonable option for women without residual disease in the hysterectomy specimen and for women with grade 1 or 2 cancer and &lt; 50% myometrial invasion, especially when no other high-risk features are present. For women with grade 1 or 2 cancer and ≥ 50% myometrial invasion or grade 3 cancer and &lt; 50% myometrial invasion, vaginal brachytherapy is as effective as pelvic radiation therapy at preventing vaginal recurrence and is preferred. Patients with grade 3 cancer and ≥ 50% myometrial invasion or cervical stroma invasion may benefit from pelvic radiation to prevent pelvic recurrence. For women with high-risk early-stage disease and advanced disease, the ASCO Endorsement Panel added qualifying statements to the ASTRO recommendations to provide stronger statements in favor of chemotherapy (with or without radiation therapy).
Measuring Quality of Life in Routine Oncology Practice Improves Communication and Patient Well-Being: A Randomized Controlled Trial
Authors: Galina Velikova, Laura Booth, Adam B. Smith, Paul M. Brown, Pamela Lynch, Julia M. Brown, Peter J. Selby
Journal: Journal of Clinical Oncology (2004)

To examine the effects on process of care and patient well-being, of the regular collection and use of health-related quality-of-life (HRQL) data in oncology practice.In a prospective study with repeated measures involving 28 oncologists, 286 cancer patients were randomly assigned to either the intervention group (regular completion of European Organization for Research and Treatment of Cancer-Core Quality of Life Questionnaire version 3.0, and Hospital Anxiety and Depression Scale on touch-screen computers in clinic and feedback of results to physicians); attention-control group (completion of questionnaires, but no feedback); or control group (no HRQL measurement in clinic before encounters). Primary outcomes were patient HRQL over time, measured by the Functional Assessment of Cancer Therapy-General questionnaire, physician-patient communication, and clinical management, measured by content analysis of tape-recorded encounters. Analysis employed mixed-effects modeling and multiple regression.Patients in the intervention and attention-control groups had better HRQL than the control group (P =.006 and P =.01, respectively), but the intervention and attention-control groups were not significantly different (P =.80). A positive effect on emotional well-being was associated with feedback of data (P =.008), but not with instrument completion (P =.12). A larger proportion of intervention patients showed clinically meaningful improvement in HRQL. More frequent discussion of chronic nonspecific symptoms (P =.03) was found in the intervention group, without prolonging encounters. There was no detectable effect on patient management (P =.60). In the intervention patients, HRQL improvement was associated with explicit use of HRQL data (P =.016), discussion of pain, and role function (P =.046).Routine assessment of cancer patients' HRQL had an impact on physician-patient communication and resulted in benefits for some patients, who had better HRQL and emotional functioning.