tbuckley/cabot-search huggingface dataset:
The angiotensin-receptor blocker candesartan for treatment of acute stroke (SCAST): a randomised, placebo-controlled, double-blind trial
Authors: Else Charlotte Sandset, Philip MW Bath, Gudrun Boysen, Dalius Jatuzis, Janika Kõrv, Stephan Lüders, Gordon D Murray, Przemyslaw S Richter, Risto O Roine, Andreas Terént, Vincent Thijs, Eivind Berge
Journal: The Lancet (2011)
Pathways Mediating Resistance to Vascular Endothelial Growth Factor–Targeted Therapy
Authors: Lee M. Ellis, Daniel J. Hicklin
Journal: Clinical Cancer Research (2008)

Abstract Vascular endothelial growth factor (VEGF)–targeted therapy has become an important treatment option for the management of a number of human malignancies. Unfortunately, a significant number of patients do not respond to VEGF-targeted therapy when used as a single agent or in combination with chemotherapy. Furthermore, the duration of benefit from VEGF-targeted therapy can be relatively short (weeks to months). Ultimately, the vast majority of patients who initially respond to therapy will develop resistance. To date, the molecular and cellular mechanisms associated with resistance to VEGF-targeted agents are poorly understood. The mechanisms of action of anti-VEGF therapy are diverse, and it is entirely possible that resistance mechanisms are similarly diverse and depend on the tumor type. A better understanding of these mechanisms will help in the selection of those patients that are more likely to benefit from VEGF-targeted therapy and also provide for the rational development of therapies that circumvent or overcome resistance.
Reply to U. Tirelli et al
Authors: Katherine S. Virgo, Catherine C. Lerro, Carrie N. Klabunde, Craig Earle, Patricia A. Ganz
Journal: Journal of Clinical Oncology (2013)

Author(s): Virgo, Katherine S; Lerro, Catherine C; Klabunde, Carrie N; Earle, Craig; Ganz, Patricia A
Genome-wide mutagenesis of Zea mays L. using RescueMu transposons.
Authors: John Fernandes, Qunfeng Dong, Bret Schneider, Darren J Morrow, Guo-Ling Nan, Volker Brendel, Virginia Walbot
Journal: Genome biology (2004)

Abstract Derived from the maize Mu1 transposon, RescueMu provides strategies for maize gene discovery and mutant phenotypic analysis. 9.92 Mb of gene-enriched sequences next to RescueMu insertion sites were co-assembled with expressed sequence tags and analyzed. Multiple plasmid recoveries identified probable germinal insertions and screening of RescueMu plasmid libraries identified plants containing probable germinal insertions. Although frequently recovered parental insertions and insertion hotspots reduce the efficiency of gene discovery per plasmid, RescueMu targets a large variety of genes and produces knockout mutants.
Application of Positron Emission Tomography in the Heart
Authors: George M. Bohigian
Journal: JAMA (1988)

This report discusses experimental and clinical applications of positron emission tomography to the heart, including measurements of blood flow to the myocardium and studies of metabolism and experimental injury. Most initial clinical studies have concentrated on ischemic heart disease, but the technique also has potential for investigation of cardiomyopathies, studying the neural control of the heart, and evaluating the effects of drugs on cardiac tissues. (<i>JAMA</i>1988;259:2438-2445)
Commentary on “Open versus closed kinetic chain exercises for patellar chondromalaciaOpen versus closed kinetic chain exercises for patellar chondromalacia”
Authors: Asghar Rezasoltani
Journal: British Journal of Sports Medicine (2008)

This study investigated and compared the effect of two different training programmes to treat patients with patellar chondromalacia. The authors initiated an intervention by applying two types of quadriceps muscle exercise therapy programmes. They measured …
The Distribution of Organs for Liver Transplantation
Authors: D. J. Norman
Journal: JAMA (1994)

Prevalence of Homes Withoul Guns, % Potentially preventable homicides and suiCIdes by prevalence of homes withou1 guns: United States.1988 through 1990.RR Indicates unadjusted risk of homICide or suicide from guns in home; and p. baseline prevalence of homes with guns.effort to kill.Also, there is no evidence of compensatory increases in homicides involving other weapons when societal firearm access is restricted.Case fatality rates for suicides attempted with a gun are much higher than for suicides attempted otherwise.s Crossnational evidence suggests that where the favored means of committing suicide is removed there is a decrease in suicide.s ~iven th~t guns are the favored means of committing suicide In the Uruted States, some people may be less likely to choose other means if denied firearm access.Suicidal people are typically ambivalent about taking their lives, and the period at risk may be fleeting.Cook's view reflects our own: "The argument here is not that the availability onethal means is the sole determinant of.suicide rates but, rather, that the availability oflethal means Influences the extent to which suicidal impulses are translated into complete suicides."sThe limitations of our approach include using risk estimates l .2 that may not accurately reflect the population's risk and not adjusting for all confounding factors (note that the adjusted risk estimates of both case-control studies were higher than the unadjusted estimates l .2).It would appear that decreasing the prevalence of guns in the home could be an important part of a national strategy to prevent homicide and suicide.
Strategies for control of trachoma: observational study with quantitative PCR
Authors: Anthony W Solomon, Martin J Holland, Matthew J Burton, Sheila K West, Neal DE Alexander, Aura Aguirre, Patrick A Massae, Harran Mkocha, Beatriz Muñoz, Gordon J Johnson, Rosanna W Peeling, Robin L Bailey, Allen Foster, David CW Mabey
Journal: The Lancet (2003)
Surgical Treatment of Aortic Regurgitation due to Takayasu Arteritis
Authors: Kaoru Matsuura, Hitoshi Ogino, Junjiro Kobayashi, Hatsue Ishibashi-Ueda, Hitoshi Matsuda, Kenji Minatoya, Hiroaki Sasaki, Ko Bando, Kazuo Niwaya, Osamu Tagusari, Hiroyuki Nakajima, Toshikatsu Yagihara, Soichiro Kitamura
Journal: Circulation (2005)

The goal of this retrospective study was to determine the late outcome of surgical treatment for aortic valve regurgitation due to Takayasu arteritis and correlate it with evidence of inflammation on pathological examination.Ninety consecutive patients who underwent surgery for aortic valve regurgitation due to Takayasu arteritis between 1979 and 2003 were studied. Intraoperative pathological specimens of the aortic wall from 69 patients were retrospectively examined for inflammation. Aortic valve replacement was performed in 63 patients (group A) and composite graft repair in 27 patients (group B). The aortic root diameter was 39.9+/-9.5 mm in group A and 54.4+/-13.6 mm in group B (P<0.0001). Preoperative steroid therapy was performed in 40 patients (44.4%). Hospital mortality was 4.8% (3/63) in group A and 7.4% (2/27) in group B. The overall 15-year survival rate was 76.1%. Detachment of the valve or graft occurred in 11.1% (7/63) of group A and in 3.7% (1/27) of group B patients (P=0.43). Late dilatation (>50 mm) of the residual ascending aorta occurred in 11.1% (7/63) of group A and in 3.7% (1/27) of group B patients (P=0.43). Active inflammation was confirmed in intraoperative pathological specimens of 10 patients, and detachment of the valve or graft occurred in 4 of these patients. Univariate analysis of background variables revealed active inflammation to be a risk factor for detachment (P=0.0001; risk ratio 55).Late dilatation of the ascending aorta after aortic valve replacement is a clinically important finding. Active inflammation could be related to valve or graft detachment.
‘Parcours de Femme 2001’: a French opinion survey on overall disease and everyday life management in 1870 women presenting with gynecological or breast cancer and their caregivers
Authors: D. Serin, J.M. Dilhuydy, P. Romestaing, N. Guiochet, J. Gledhill, P. Bret, J. Savary, A. Flinois
Journal: Annals of Oncology (2004)

The aim of the survey 'Parcours de Femmes 2001' was to evaluate the overall management and care of women with female cancers and to determine their needs.Women with breast or gynecological cancer who had either received at least 3 months of treatment or had completed treatment <1 year before the study were enrolled in this cross-sectional, observational study.From February to November 2001, 2839 questionnaires were distributed; 1870 were returned (66% response rate), mainly by breast cancer patients (87%). While 92% of women reported having received information at diagnosis, 34% of relapsed patients complained of lack of information concerning their disease and treatment. Only 18% of patients were included in the treatment decision process and 66% of women obtained complementary information from the media, patients and care professionals. Fatigue was the most severe problem quoted (78% of cases) and was poorly managed by caregivers due to diagnostic and treatment difficulties. Problems relating to family and to affective and socio-professional life were poorly identified and remained largely unmanaged.Information given to female cancer patients must be improved in relapsed patients, particularly regarding the adverse effects of treatment. Psychosocial management requires a more holistic approach through new channels, together with the coordination of existing structures.
Identification of Factors Associated With Sural Nerve Regeneration and Degeneration in Diabetic Neuropathy
Authors: Junguk Hur, Kelli A. Sullivan, Brian C. Callaghan, Rodica Pop-Busui, Eva L. Feldman
Journal: Diabetes Care (2013)

Patients with diabetic neuropathy (DN) demonstrate variable degrees of nerve regeneration and degeneration. Our aim was to identify risk factors associated with sural nerve degeneration in patients with DN.Demographic, anthropometric, biochemical, and anatomical data of subjects with DN from a 52-week trial of acetyl-L-carnitine were retrospectively examined. Based on the change in sural nerve myelinated fiber density (ΔMFD%), subjects were divided into three groups: regenerator (top 16 percentiles, n = 67), degenerator (bottom 16 percentiles, n = 67), and intermediate (n = 290), with dramatically increased, decreased, and steady ΔMFD%, respectively. ANOVA, Fisher exact test, and multifactorial logistic regression were used to evaluate statistical significance.ΔMFD%s were 35.6 ± 17.4 (regenerator), -4.8 ± 12.1 (intermediate), and -39.8 ± 11.0 (degenerator). HbA1c at baseline was the only factor significantly different across the three groups (P = 0.01). In multifactorial logistic regression, HbA1c at baseline was also the only risk factor significantly different between regenerator (8.3 ± 1.6%) and degenerator (9.2 ± 1.8%) (odds ratio 0.68 [95% CI 0.54-0.85]; P < 0.01). Support Vector Machine classifier using HbA1c demonstrated 62.4% accuracy of classifying subjects into regenerator or degenerator. A preliminary microarray experiment revealed that upregulated genes in the regenerator group are enriched with cell cycle and myelin sheath functions, while downregulated genes are enriched in immune/inflammatory responses.These data, based on the largest cohort with ΔMFD% information, suggest that HbA1c levels predict myelinated nerve fiber regeneration and degeneration in patients with DN. Therefore, maintaining optimal blood glucose control is likely essential in patients with DN to prevent continued nerve injury.
Characterization of <i>KRAS</i> Rearrangements in Metastatic Prostate Cancer
Authors: Xiao-Song Wang, Sunita Shankar, Saravana M. Dhanasekaran, Bushra Ateeq, Atsuo T. Sasaki, Xiaojun Jing, Daniel Robinson, Qi Cao, John R. Prensner, Anastasia K. Yocum, Rui Wang, Daniel F. Fries, Bo Han, Irfan A. Asangani, Xuhong Cao, Yong Li, Gilbert S. Omenn, Dorothee Pflueger, Anuradha Gopalan, Victor E. Reuter, Emily Rose Kahoud, Lewis C. Cantley, Mark A. Rubin, Nallasivam Palanisamy, Sooryanarayana Varambally, Arul M. Chinnaiyan
Journal: Cancer Discovery (2011)

Using an integrative genomics approach called amplification breakpoint ranking and assembly analysis, we nominated KRAS as a gene fusion with the ubiquitin-conjugating enzyme UBE2L3 in the DU145 cell line, originally derived from prostate cancer metastasis to the brain. Interestingly, analysis of tissues revealed that 2 of 62 metastatic prostate cancers harbored aberrations at the KRAS locus. In DU145 cells, UBE2L3-KRAS produces a fusion protein, a specific knockdown of which attenuates cell invasion and xenograft growth. Ectopic expression of the UBE2L3-KRAS fusion protein exhibits transforming activity in NIH 3T3 fibroblasts and RWPE prostate epithelial cells in vitro and in vivo. In NIH 3T3 cells, UBE2L3-KRAS attenuates MEK/ERK signaling, commonly engaged by oncogenic mutant KRAS, and instead signals via AKT and p38 mitogen-activated protein kinase (MAPK) pathways. This is the first report of a gene fusion involving the Ras family, suggesting that this aberration may drive metastatic progression in a rare subset of prostate cancers.This is the first description of an oncogenic gene fusion of KRAS, one of the most studied proto-oncogenes. KRAS rearrangement may represent the driving mutation in a rare subset of metastatic prostate cancers, emphasizing the importance of RAS-RAF-MAPK signaling in this disease.
Recent advances in hearing restoration
Authors: Kunal Kulkarni, Douglas EH Hartley
Journal: Journal of the Royal Society of Medicine (2008)

Summary This review is based on Pubmed, Medline and Internet literature searches, supplemented by knowledge from textbooks, conference presentations, and personal communications with experts in the field of hearing restoration and patients. We have not specifically selected a time limit for our literature searches; however, the majority are articles from the past 5 years.
Physical Activity Improves Long-Term Stroke Outcome via Endothelial Nitric Oxide Synthase–Dependent Augmentation of Neovascularization and Cerebral Blood Flow
Authors: Karen Gertz, Josef Priller, Golo Kronenberg, Klaus B. Fink, Benjamin Winter, Helmut Schröck, Shengbo Ji, Milan Milosevic, Christoph Harms, Michael Böhm, Ulrich Dirnagl, Ulrich Laufs, Matthias Endres
Journal: Circulation Research (2006)

Physical activity upregulates endothelial nitric oxide synthase (eNOS), improves endothelium function, and protects from vascular disease. Here, we tested whether voluntary running would enhance neovascularization and long-term recovery following mild brain ischemia. Wild-type mice were exposed to 30 minutes of middle-cerebral artery occlusion (MCAo) and reperfusion. Continuous voluntary running on wheels conferred long-term upregulation of eNOS in the vasculature and of endothelial progenitor cells (EPCs) in the spleen and bone marrow (BM). This was associated with higher numbers of circulating EPCs in the blood and enhanced neovascularization. Moreover, engraftment of TIE2/LacZ-positive BM-derived cells was increased in the ischemic brain. Four weeks after the insult, trained animals showed higher numbers of newly generated cells in vascular sites, increased density of perfused microvessels and sustained augmentation of cerebral blood flow within the ischemic striatum. Moreover, running conferred tissue sparing and improved functional outcome at 4 weeks. The protective effects of running on angiogenesis and outcome were completely abolished when animals were treated with a NOS inhibitor or the antiangiogenic compound endostatin after brain ischemia, and in animals lacking eNOS expression. Voluntary physical activity improves long-term stroke outcome by eNOS-dependent mechanisms related to improved angiogenesis and cerebral blood flow.
EXPERIMENTAL STUDIES OF THE NASOPHARYNGEAL SECRETIONS FROM INFLUENZA PATIENTS
Authors: Peter K. Olitsky, Frederick L. Gates
Journal: The Journal of Experimental Medicine (1923)

Although Bacterium pneumosintes is a stable organism which agglutinates only in low dilutions of the serum of actively immunized rabbits, the serological reactions of this microorganism have always been found to be consistent and specific. The results of the agglutination and precipitation reactions described in this paper indicate that the serum of normal persons does not contain demonstrable agglutinins or precipitins for Bacterium pneumosintes. By contrast, agglutinins have been demonstrated in the serum of seventeen persons among nineteen who were examined from 10 days to 5 months after recovery from epidemic influenza. The serum of ten persons who had influenza, followed in three instances by pneumonia, 2(1/2) to 3(1/2) years before, proved negative. In one instance the appearance of specific agglutinins against Bacterium pneumosintes was found to be coincident with an attack of uncomplicated influenza. In twelve of fifteen instances in which agglutinins were found, precipitins against Bacterium pneumosintes were demonstrated also. It is noteworthy that these antibodies may persist in the blood at least 5 months after recovery from the disease.
Arrestin-Independent Internalization and Recycling of the Urotensin Receptor Contribute to Long-Lasting Urotensin II–Mediated Vasoconstriction
Authors: Günter Giebing, Markus Tölle, Jana Jürgensen, Jenny Eichhorst, Jens Furkert, Michael Beyermann, Frank Neuschäfer-Rube, Walter Rosenthal, Walter Zidek, Markus van der Giet, Alexander Oksche
Journal: Circulation Research (2005)

Urotensin II (UII), which acts on the G protein-coupled urotensin (UT) receptor, elicits long-lasting vasoconstriction. The role of UT receptor internalization and intracellular trafficking in vasoconstriction has yet not been analyzed. Therefore, UII-mediated contractile responses of aortic ring preparations in wire myography and rat UT (rUT) receptor internalization and intracellular trafficking in binding and imaging analyses were compared. UII elicited a concentration-dependent vasoconstriction of rat aorta (−log EC50, mol/L:9.0±0.1). A second application of UII after 30 minutes elicited a reduced contraction (36±4% of the initial response), but when applied after 60 minutes elicited a full contraction. In internalization experiments with radioactive labeled VII ( 125 I-UII), ≈70% of rUT receptors expressed on the cell surface of human embryonic kidney 293 cells were sequestered within 30 minutes (half life [t h ]: 5.6±0.2 minutes), but recycled quantitatively within 60 minutes (t h 31.9±2.6 minutes). UII-bound rUT receptors were sorted to early and recycling endosomes, as evidenced by colocalization of rUT receptors with the early endosomal antigen and the transferrin receptor. Real-time imaging with a newly developed fluorescent UII (Cy3-UII) revealed that rUT receptors recruited arrestin3 green fluorescent protein to the plasma membrane. Arrestin3 was not required for the endocytosis of the rUT receptor, however, as internalization of Cy3-UII was not altered in mouse embryonic fibroblasts lacking endogenous arrestin2/arrestin3 expression. The data demonstrate that the rUT receptor internalizes arrestin independently and recycles quantitatively. The continuous externalization of rUT receptors provides the basis for repetitive and lasting UII-mediated vasoconstriction.
European registry of babies born to mothers with antiphospholipid syndrome
Authors: Arsene Mekinian, Eric Lachassinne, Pascale Nicaise-Roland, Lionel Carbillon, Mario Motta, Eric Vicaut, Catherine Boinot, Tadej Avcin, Philippe Letoumelin, Sara De Carolis, Patrizia Rovere-Querini, Marc Lambert, Sophie Derenne, Olivier Pourrat, Jerome Stirnemann, Sylvie Chollet-Martin, Chiara Biasini-Rebaioli, Rosanna Rovelli, Andrea Lojacono, Ales Ambrozic, Angela Botta, Amelie Benbara, Fabrice Pierre, Flavio Allegri, Monica Nuzzo, Pierre-Yves Hatron, Angela Tincani, Olivier Fain, Marie-Helene Aurousseau, Marie-Claire Boffa
Journal: Annals of the Rheumatic Diseases (2012)

This study aimed to describe the long-term outcome and immunological status of children born to mothers with antiphospholipid syndrome, to determine the factors responsible for childhood abnormalities, and to correlate the child's immunological profile with their mothers.A prospective follow-up of a European multicentre cohort was conducted. The follow-up consisted of clinical examination, growth data, neurodevelopmental milestones and antiphospholipid antibodies (APL) screening. Children were examined at 3, 9, 24 months and 5 years.134 children were analysed (female sex in 65 cases, birth weight 3000±500 g, height 48±3 cm). Sixteen per cent had a preterm birth (<37 weeks; n=22), and 14% weighted less than 2500 g at birth (n=19). Neonatal complications were noted in 18 cases (13%), with five infections (4%). During the 5-year follow-up, no thrombosis or systemic lupus erythematosus (SLE) was noted. Four children displayed behavioural abnormalities, which consisted of autism, hyperactive behaviour, feeding disorder with language delay and axial hypotony with psychomotor delay. At birth lupus anticoagulant was present in four (4%), anticardiolipin antibodies (ACL) IgG in 18 (16%), anti-β(2) glycoprotein-I (anti-β2GPI) IgG/M in 16 (15%) and three (3%), respectively. ACL IgG and anti-β2GPI disappeared at 6 months in nine (17%) and nine (18%), whereas APL persisted in 10% of children. ACL and anti-β2GPI IgG were correlated with the same mother's antibodies before 6 months of age (p<0.05).Despite the presence of APL in children, thrombosis or SLE were not observed. The presence of neurodevelopmental abnormalities seems to be more important in these children, and could justify long-term follow-up.
Human reproductive strategies: An emerging synthesis?
Authors: Marco Del Giudice
Journal: Behavioral and Brain Sciences (2009)

Abstract In the first part of this response, commentators' critiques to the target article are reviewed and addressed. The main discussion topics are the role of attachment in developmental plasticity; the relationship between attachment, mating, and reproductive strategies; the existence, magnitude, and developmental timing of sex differences in attachment; the adaptiveness of insecure styles; and the neurobiology of attachment and reproduction. The model's assumptions are clarified, and a number of methodological issues that can confound the interpretation of research findings are examined. In the second part, various proposals made by commentators are synthesized, and directions for future research and theoretical improvement are outlined. In addition, the issue of disorganized and fearful attachment is tentatively addressed. It is argued that different theoretical perspectives are converging toward a consistent and comprehensive theory of human reproductive strategies.