tbuckley/cabot-search huggingface dataset:
The Phenotypic and Genetic Structure of Depression and Anxiety Disorder Symptoms in Childhood, Adolescence, and Young Adulthood
Authors: Monika A. Waszczuk, Helena M. S. Zavos, Alice M. Gregory, Thalia C. Eley
Journal: JAMA Psychiatry (2014)

The DSM-5 classifies mood and anxiety disorders as separate conditions. However, some studies in adults find a unidimensional internalizing factor that underpins anxiety and depression, while others support a bidimensional model where symptoms segregate into distress (depression and generalized anxiety) and fear factors (phobia subscales). However, little is known about the phenotypic and genetic structure of internalizing psychopathology in children and adolescents.To investigate the phenotypic associations between depression and anxiety disorder symptom subscales and to test the genetic structures underlying these symptoms (DSM-5-related, unidimensional and bidimensional) across 3 developmental stages: childhood, adolescence, and early adulthood.Two population-based prospective longitudinal twin/sibling studies conducted in the United Kingdom. The child sample included 578 twins (mean age, approximately 8 and 10 years at waves 1 and 2, respectively). The adolescent and early adulthood sample included 2619 twins/siblings at 3 waves (mean age, 15, 17, and 20 years at each wave).Self-report symptoms of depression and anxiety disorders.Phenotypically, when controlling for other anxiety subscales, depression symptoms were only associated with generalized anxiety disorder symptoms in childhood (r = 0.20-0.21); this association broadened to panic and social phobia symptoms in adolescence (r = 0.17-0.24 and r = 0.14-0.16, respectively) and all anxiety subscales in young adulthood (r = 0.06-0.19). The genetic associations were in line with phenotypic results. In childhood, anxiety subscales were influenced by a single genetic factor that did not contribute to genetic variance in depression symptoms, suggesting largely independent genetic influences on anxiety and depression. In adolescence, genetic influences were significantly shared between depression and all anxiety subscales in agreement with DSM-5 conceptualization. In young adulthood, a genetic internalizing factor influencing depression and all anxiety subscales emerged, alongside a small significant genetic fear factor.These results provide preliminary evidence for different phenotypic and genetic structures of internalizing disorder symptoms in childhood, adolescence, and young adulthood, with depression and anxiety becoming more associated from adolescence. The results inform molecular genetics research and transdiagnostic treatment approaches. The findings affirm the need to continue examining the classification of mood and anxiety disorders in diagnostic systems.
Long-term efficacy of early versus delayed radiotherapy for low-grade astrocytoma and oligodendroglioma in adults: the EORTC 22845 randomised trial
Authors: MJ van den Bent, D Afra, O de Witte, M Ben Hassel, S Schraub, K Hoang-Xuan, P-O Malmström, L Collette, M Piérart, R Mirimanoff, ABMF Karim
Journal: The Lancet (2005)
A phase I/II and pharmacokinetic study of irinotecan in combination with capecitabine as first-line therapy for advanced colorectal cancer
Authors: D.W. Rea, J.W.R. Nortier, W.W. Ten Bokkel Huinink, S. Falk, D.J. Richel, T. Maughan, G. Groenewegen, J.M. Smit, N. Steven, J.M. Bakker, D. Semiond, D.J. Kerr, C.J.A. Punt
Journal: Annals of Oncology (2005)
VEGF Gene Delivery to Myocardium
Authors: Randall J. Lee, Matthew L. Springer, William E. Blanco-Bose, Robin Shaw, Philip C. Ursell, Helen M. Blau
Journal: Circulation (2000)

Vascular endothelial growth factor (VEGF) is being investigated for therapeutic angiogenesis in ischemic myocardium. Primarily, transient delivery systems have been tested. The goal of this study was to investigate the effects of continuous expression of VEGF in myocardium by use of myoblast-mediated delivery.Primary murine myoblasts (5 x 10(5) cells in 10 microL of PBS with 0.5% BSA) expressing both the murine VEGF gene and the beta-galactosidase (beta-gal) gene from a retroviral promoter were implanted in the ventricular wall of immunodeficient mice (n=11) via a subdiaphragmatic approach. Control immunodeficient mice (n=12) were injected with the same number of myoblasts expressing only the beta-gal gene. Between days 14 and 16, surviving mice were euthanized and the hearts processed for histology. In the experimental group, 11 of 11 mice demonstrated failure to thrive by day 13; 5 deaths occurred between days 8 and 15. There were no complications in the control mice. Histochemistry documented successful implantation of myoblasts (positive beta-gal reaction product) in 6 of 6 surviving experimental mice and 12 of 12 controls. Histology disclosed intramural vascular tumors resembling hemangiomas in the VEGF-myoblast-injected myocardium in 6 of 6 surviving mice. beta-Gal-expressing cells were present at the site of the vascular tumors. Immunohistochemistry localized abundant endothelial nitric oxide synthase and CD31 (platelet and endothelial cell adhesion molecule) within the lesion, consistent with the presence of endothelial cells.In this model, unregulated continuous expression of VEGF is associated with (1) a high rate of failure to thrive/death and (2) formation of endothelial cell-derived intramural vascular tumors in the implantation site. These results underscore the importance of regulating VEGF expression for therapeutic angiogenesis.
Physiological Observations During Induced Dyspnea
Authors: ALBERT J. WASSERMAN, Joux L. PATTERSON
Journal: Circulation Research (1961)

In 17 iiormal subjects, dyspiiea was induced by exercise at 500 Kg.-M. per minute, with added external airway resistance. Arterial blood gas tensions and p transpulmonary I)reSsure, and pulmonary ventilation were measured iii the control period, at the onset of dyspnea, and at the disappearance of dysp ilea, which followedi cessation of exercise. Close correlation of the symptom with the functions measured was obtained through the use of hand signals by the subject to denote the onset and disappearance of ally unpleas ant sensation. The meaning of the signals was later obtained liv description. Except for a difference in time required for the devel opment of dyspnea, the results were similar whether the subject was exercised in the Su pine or in the 65-degree head-up position. In every instance, while the subjects were breath ing air, at the time of appearance of dyspnea, the arterial oxygen tension had fallen below control, levels, and at the disappearance of the symptom, the oxygen tension had returned to or near the control value. No such correla tion was obtanieci between the symptom mid the other variables measured. Subjects who did not develop dyspnea showed no fall ill arterial oxygen tension. The subjects exer (Ismg while breathing 100 per cent oxygen required longer periods for the development of dyspnea, and six of eight subjects who de veloped clysl)llea while breathing air experi enced partial Or complete relief of dyspnea despite the continuance of exercise when, un known to them, the inspired gas was switched from air to 1.00 Per cent oxygen. These resuggest that dyspnea, under the conditions of these experiments, was related to the sum- mated load of respiratory stimuli. In these experiments, the arterial oxygen tension ap pareritly was the critical variable.
INTRAVENTRICULAR GENTAMICIN IN MENINGITIS
Authors: AllenB. Kaiser, PeterF. Wright, ZellA. Mcgee, WilliamD. Dupont, R.E. Warren, N.R.C. Roberton, L. Corbeel, K. De Boeck, N. Logghe, E. Eggermont, R. Eeckels, P. Casaer, J. Vandepitte, L. Verbist, Wilhelm Frederiksen, Per Schouenborg, GeorgeH. McCracken, SusanG. Mize
Journal: The Lancet (1980)
Progress Toward Embracing Exercise Training As an Integral Part of Prostate Cancer Treatment
Authors: Liam Bourke, Phillip K. Dahm, Derek J. Rosario
Journal: Journal of Clinical Oncology (2014)

We were encouraged to read the recently published systematic review by Gardner et al 1 concerning the beneficial effects of exercise training interventions on physical function and fatigue in men undergoing androgen-deprivation therapy (ADT) for prostate cancer.Although we share the author's general conclusion, several important issues deserve the readers' attention.First, through no fault of the authors, but given the time lapse between the latest literature update (June 2013) and the date of publication (December 2013), two recent randomized controlled trials 2,3 (RCTs) that were published in October 2013 were not evaluated.This is unfortunate, given the general rarity of RCTs in this arena, because the finding of clinically relevant improvements in prostate cancerspecific quality of life in one of the studies was noteworthy, particularly because that study has been the only RCT to explicitly include sedentary men with documented metastatic disease receiving long-term ADT. 2 Second, the relatively uncritical side-by-side presentation of evidence that was derived from experimental and observational study designs and the failure to rate the quality of evidence on an outcomespecific basis are concerns. 4Finally, efforts toward a meta-analysis of RCT data using standardized effect size measures for select outcomes could have greatly improved the practical value of this important review. 5A Cochrane systematic review using a rigorous peer-reviewed methodology, which will also evaluate any available non-Englishlanguage manuscripts, is ongoing and is expected to address these issues later this year.Many in the field are particularly excited about the potential benefit of exercise training in regard to the effect on disease progression.The editorial by Parsons 6 that accompanied the study by Gardner et al 1 highlighted this but suggested that there are no planned randomized trials in the field to address this issue.We are pleased to announce the Prostate Cancer Novel Therapy (PANTERA) trial has recently been granted support by Cancer Research United Kingdom.This study will evaluate the effect of 12 months of aerobic exercise training on disease progression and time to invasive therapy in men with low-and intermediate-risk localized prostate cancer undergoing active surveillance, with the first phase focusing on feasibility of the intervention.We look forward to seeing treating urologists and oncologists begin to embrace the growing evidence for the beneficial effects of exercise training in men with prostate cancer, and we also eagerly anticipate a commitment from health care providers to support the integration of such interventions as the standard in cancer treatment.
Omitting Radiotherapy in Early Positron Emission Tomography–Negative Stage I/II Hodgkin Lymphoma Is Associated With an Increased Risk of Early Relapse: Clinical Results of the Preplanned Interim Analysis of the Randomized EORTC/LYSA/FIL H10 Trial
Authors: John M.M. Raemaekers, Marc P.E. André, Massimo Federico, Theodore Girinsky, Reman Oumedaly, Ercole Brusamolino, Pauline Brice, Christophe Fermé, Richard van der Maazen, Manuel Gotti, Reda Bouabdallah, Catherine J. Sebban, Yolande Lievens, Allessandro Re, Aspasia Stamatoullas, Frank Morschhauser, Pieternella J. Lugtenburg, Elisabetta Abruzzese, Pierre Olivier, Rene-Olivier Casasnovas, Gustaaf van Imhoff, Tiana Raveloarivahy, Monica Bellei, Thierry van der Borght, Stephane Bardet, Annibale Versari, Martin Hutchings, Michel Meignan, Catherine Fortpied
Journal: Journal of Clinical Oncology (2014)

Purpose Combined-modality treatment is standard treatment for patients with clinical stage I/II Hodgkin lymphoma (HL). We hypothesized that an early positron emission tomography (PET) scan could be used to adapt treatment. Therefore, we started the randomized EORTC/LYSA/FIL Intergroup H10 trial evaluating whether involved-node radiotherapy (IN-RT) could be omitted without compromising progression-free survival in patients attaining a negative early PET scan after two cycles of ABVD (doxorubicin, bleomycin, vinblastine, and dacarbazine) as compared with standard combined-modality treatment. Patients and Methods Patients age 15 to 70 years with untreated clinical stage I/II HL were eligible. Here we report the clinical outcome of the preplanned interim futility analysis scheduled to occur after documentation of 34 events in the early PET–negative group. Because testing for futility in this noninferiority trial corresponds to testing the hypothesis of no difference, a one-sided superiority test was conducted. Results The analysis included 1,137 patients. In the favorable subgroup, 85.8% had a negative early PET scan (standard arm, one event v experimental arm, nine events). In the unfavorable subgroup, 74.8% had a negative early PET scan (standard arm, seven events v experimental arm, 16 events). The independent data monitoring committee concluded it was unlikely that we would show noninferiority in the final results for the experimental arm and advised stopping random assignment for early PET–negative patients. Conclusion On the basis of this analysis, combined-modality treatment resulted in fewer early progressions in clinical stage I/II HL, although early outcome was excellent in both arms. The final analysis will reveal whether this finding is maintained over time.
Circulatory Responses to Electrical and Reflex Activation of the Nervous System after Cardiac Denervation
Authors: CLARENCE N. PEISS, THEODORE COOPER, V. L. WILLMAN, WALTER C. RANDALL
Journal: Circulation Research (1966)

Rigorous testing procedures assessed the extent of extrinsic cardiac denervation in three groups of animals subjected to cardiac extirpation and reimplantation (E&amp;R), mediastinal neural ablation (MNA) or thoracic ganglionectomy (BSTG). After E&amp;R, all dogs were completely denervated. Evidence for vagal reinnervation appeared as early as 26 days and for both vagal and sympathetic reinnervation in 74 days. After one, two and three years, the functional responses to reflex and electrical activation of the nervous system were similar to those in normal dogs. After MNA, only one animal of eight was totally denervated. Seven showed varying degrees of cardiac activation in response to diencephalic stimulation or stimulation of the cardiac sympathetic nerves. Thus MNA, though surgically feasible, cannot be assumed to be successful without rigorous testing. After BSTG, four of eight dogs showed complete separation of sympathetic cardiac outflow from the CNS; in all eight, moderate to large cardio-accelerator responses were elicited from the distal vagosympathetic trunk after atropinization. There is little correlation between the over-all cardiac responses persisting in all operated animals and total cardiac catecholamine content, or between cardio-accelerator responses and right atrial catecholamine content.
Epidemiology of injuries and illnesses in America’s Cup yacht racing
Authors: V J Neville, J Molloy, J H M Brooks, D B Speedy, G Atkinson
Journal: British Journal of Sports Medicine (2006)

Objectives: To determine the incidence and severity of injuries and illnesses incurred by a professional America’s Cup yacht racing crew during the preparation for and participation in the challenge for the 2003 America’s Cup. Methods: A prospective study design was used over 74 weeks of sailing and training. All injuries and illnesses sustained by the 35 professional male crew members requiring medical treatment were recorded, including the diagnosis, nature, location, and mechanism of injury. The volume of sailing and training were recorded, and the severity of incidents were determined by the number of days absent from both sailing and training. Results: In total, 220 injuries and 119 illnesses were recorded, with an overall incidence of 8.8 incidents/1000 sailing and training hours (injuries, 5.7; illnesses, 3.1). The upper limb was the most commonly injured body segment (40%), followed by the spine and neck (30%). The most common injuries were joint/ligament sprains (27%) and tendinopathies (20%). The incidence of injury was significantly higher in training (8.6) than sailing (2.2). The most common activity or mechanism of injury was non-specific overuse (24%), followed by impact with boat hardware (15%) and weight training (13%). “Grinders” had the highest overall injury incidence (7.7), and “bowmen” had the highest incidence of sailing injuries (3.2). Most of the illnesses were upper respiratory tract infections (40%). Conclusions: The data from this study suggest that America’s Cup crew members are at a similar risk of injury to athletes in other non-collision team sports. Prudent allocation of preventive and therapeutic resources, such as comprehensive health and medical care, well designed conditioning and nutritional programmes, and appropriate management of recovery should be adopted by America’s Cup teams in order to reduce the risk of injury and illness.
CHARACTERIZATION OF CYSTIC FIBROSIS FACTOR AND ITS INTERACTION WITH HUMAN IMMUNOGLOBULIN
Authors: B. Shannon Danes, Stephen D. Litwin, Thomas H. Hütteroth, Hartwig Cleve, Alexander G. Bearn
Journal: The Journal of Experimental Medicine (1973)

Cystic fibrosis factor activity (CFFA), assayed as the ability to stop oyster ciliary movement, was present in serum-free medium from actively growing cystic fibrosis skin fibroblast cultures. CFFA was associated with a low molecular weight, negatively charged molecule that contained no uronic acid and was heat and pH labile. When CFFA-positive media were mixed with human IgG1, the CFFA was chromatographically displaced and emerged with the IgG1 fraction on column chromatography. Experiments in which various immunoglobulins were added to CFFA-positive culture media and then incubated with specific anti-immunoglobulins suggested that CFFA binding was class specific for human IgG, subclass specific for IgG1 and IgG2, and occurred with intact unaggregated heavy chains but not with κ- and λ-light chains, or Fab, Fc, and F(ab')2 fragments. The serum protein ß2-microglobulin, which has structural homology to IgG, also bound CFFA.
Metastasis Suppressor Function of Tumor Necrosis Factor–Related Apoptosis-Inducing Ligand-R in Mice: Implications for TRAIL-Based Therapy in Humans?
Authors: Anne Grosse-Wilde, Christopher J. Kemp
Journal: Cancer Research (2008)

Abstract Tumor necrosis factor–related apoptosis-inducing ligand (TRAIL) is a promising candidate for cancer therapy, as it can induce apoptosis specifically in tumor cells but not in normal cells. Although earlier mouse tumor studies revealed a strong tissue dependency of TRAIL and its death receptor in suppressing primary tumorigenesis or experimental metastases, we recently found that TRAIL-R inhibits lymph node metastases without affecting primary tumor formation in a mouse model of multistage skin tumorigenesis. This finding uncouples the role of TRAIL in primary tumorigenesis from metastasis formation, likely by sensitization of previously TRAIL-resistant tumor cells upon detachment, an early step required for metastasis formation. Therefore, TRAIL-R is a novel metastasis suppressor, suggesting that TRAIL-related tumor therapy might be most effective in primary tumors and early metastatic cancers, before selection for TRAIL resistance occurs. [Cancer Res 2008;68(15):6035–7]
Acid-Base Transport by the Renal Proximal Tubule
Authors: Walter F. Boron
Journal: Journal of the American Society of Nephrology (2006)

One of the major tasks of the renal proximal tubule is to secrete acid into the tubule lumen, thereby reabsorbing approximately 80% of the filtered HCO3- as well as generating new HCO3- for regulating blood pH. This review summarizes the cellular and molecular events that underlie four major processes in HCO3- reabsorption. The first is CO2 entry across the apical membrane, which in large part occurs via a gas channel (aquaporin 1) and acidifies the cell. The second process is apical H+ secretion via Na-H exchange and H+ pumping, processes that can be studied using the NH4+ prepulse technique. The third process is the basolateral exit of HCO3- via the electrogenic Na/HCO3 co-transporter, which is the subject of at least 10 mutations that cause severe proximal renal tubule acidosis in humans. The final process is the regulation of overall HCO3- reabsorption by CO2 and HCO3- sensors at the basolateral membrane. Together, these processes ensure that the proximal tubule responds appropriately to acute acid-base disturbances and thereby contributes to the regulation of blood pH.
Personality pattern and emotional stress in the genesis of gastric ulcer
Authors: M. H. Alp, J. H. Court, A. K. Grant
Journal: Gut (1970)

In a group of 181 persons with a past history of chronic gastric ulcer, a greatly increased incidence of domestic and financial stress has been found, when compared with age-and sex-matched persons with no previous history of gastric ulcer. The consumption of aspirin, alcohol, and cigarettes was also significantly increased. Persons with chronic gastric ulcer were characterized by a personality pattern of independence and self sufficiency, and they are prone to anxiety and depression. This pattern was three times as common as in matched individuals without chronic gastric ulcer. It is possible that internal conflict between a genetic and an environmentally induced sex role, together with an inability to externalize aggression, may be significant factors in the causation of chronic gastric ulcer.
Lung microbiome and disease progression in idiopathic pulmonary fibrosis: an analysis of the COMET study
Authors: MeiLan K Han, Yueren Zhou, Susan Murray, Nabihah Tayob, Imre Noth, Vibha N Lama, Bethany B Moore, Eric S White, Kevin R Flaherty, Gary B Huffnagle, Fernando J Martinez
Journal: The Lancet Respiratory Medicine (2014)
Acute effects of cigarette smoke on inflammation and oxidative stress: a review
Authors: H van der Vaart, D S Postma, W Timens, N H T ten Hacken
Journal: Thorax (2004)

Compared with the effects of chronic smoke exposure on lung function and airway inflammation, there are few data on the acute effects of smoking. A review of the literature identified 123 studies investigating the acute effects of cigarette smoking on inflammation and oxidative stress in human, animal, and in vitro models. An acute smoking model is a relatively easy and sensitive method of investigating the specific effects of cigarette smoke on oxidative stress and inflammation. Acute smoke exposure can result in tissue damage, as suggested by increased products of lipid peroxidation and degradation products of extracellular matrix proteins. Acute cigarette smoke has a suppressive effect on the number of eosinophils and several inflammatory cytokines, possibly due to the anti-inflammatory effect of carbon monoxide. An acute smoking model can supplement other ways of studying the effects of smoking and is an as yet underinvestigated method for intervention studies in smoking related diseases.