tbuckley/cabot-search huggingface dataset:
Abdominal Aortic Aneurysm Expansion
Authors: Anthony R. Brady, Simon G. Thompson, F. Gerald R. Fowkes, Roger M. Greenhalgh, Janet T. Powell
Journal: Circulation (2004)

Intervention to reduce abdominal aortic aneurysm (AAA) expansion and optimization of screening intervals would improve current surveillance programs. The aim of this study was to characterize AAA growth in a national cohort of patients with AAA both overall and by cardiovascular risk factors.In this study, 1743 patients were monitored for changes in AAA diameter by ultrasonography over a mean follow-up of 1.9 years. Mean initial AAA diameter and growth rate were 43 mm (range 28 to 85 mm) and 2.6 mm/year (95% range, -1.0 to 6.1 mm/year), respectively. Baseline diameter was strongly associated with growth, suggesting that AAA growth accelerates as the aneurysm enlarges. AAA growth rate was lower in those with low ankle/brachial pressure index and diabetes but higher for current smokers (all P<0.001). No other factor (including lipids and blood pressure) was associated with AAA growth. Intervals of 36, 24, 12, and 3 months for aneurysms of 35, 40, 45, and 50 mm, respectively, would restrict the probability of breaching the 55-mm limit at rescreening to below 1%.Annual, or less frequent, surveillance intervals are safe for all AAAs < or =45 mm in diameter. Smoking increases AAA growth, but atherosclerosis plays a minor role.
THALLIUM ACETATE AS A DEPILATORY IN RINGWORM OF THE SCALP
Authors: H. M. Mitchell
Journal: BMJ (1930)

Experiments were made with milaniy methods of preven- tioIi.The Seliultz-Charlton test miierely corroborated what wi.as uisuially know-n-namely, that a briglht rash indicated scarlet fevler; the Dick test uwas found to be of little value iii. the positive cases-wlhere the immu-nitv had n-ot had ttime to develop or where there was susceptibility to the di,ease.If the Dick test is repeated at the end of a week s',eful information is obtained, b-ut suisceptible patients are mneanw-hile exposed to infection.Active immunizationi by means of scarlet fe-er prophylactic develops too slowly to be of any real value; andl barrier isolation, though em- p)loyed to some pJuipose, was ineffective in wards where all the patients were niot confined to bed.'T'he productioni of passive immuiiitv by means of scarlet feve-r antitoxin was then considered.A ssmall dose was said to gi-e a passive immunity for ten to fourteen days.This period was not considered to be long enouigh, as " peeling in many mild cases often -does niot occu1r until about the fou,1rth wveek.If a dose is repeated w-ithiin ten days there il)l)e.rs to be no danger of anaphlax-is, as senisitizationl to ,a foreign protein does not begini uiitil after that period.T'lie r'isk was lessened by admiiinistlerinlg onily 2.1.c.cm. at first.
Effect of improved housing on illness in children under 5 years old in northern Malawi: cross sectional study
Authors: C. G Wolff
Journal: BMJ (2001)

<h3>Abstract</h3> <b>Objective:</b> To evaluate the effects of a Habitat for Humanity housing improvement programme in northern Malawi on the prevalence of childhood illnesses. <b>Design:</b> Household based cross sectional study. <b>Setting:</b> Rural communities centred near the small northern Malawi town of Ekwendeni. <b>subjects:</b> 318 children under 5 years old. <b>Main outcome measures:</b> Prevalence of respiratory, gastrointestinal, and malarial infections according to maternal recall, laboratory, or clinical data. <b>Results:</b> Children living in improved homes were less likely to have respiratory, gastrointestinal, or malarial illnesses (odds ratio 0.56, 95% confidence interval 0.35 to 0.91) after confounding factors were controlled for. The reductions in individual diseases were not significant. <b>Conclusion:</b> Improved housing significantly reduced the burden of disease among children under 5 years old. <h3>What is already known on this topic</h3> Poor quality housing is generally accepted as an important contributor to ill health Few designed studies have quantified the impact of improved housing on health in the developing world <h3>What this study adds</h3> Improved housing reduced the odds of respiratory infection, gastrointestinal illness, or malaria by 44% in children under 5 years old The reductions in individual illnesses were not significant Housing development programmes are an important component of efforts to improve global health
Dietary fish oil as a photoprotective agent in hydroa vacciniforme
Authors: None Rhodes, None White
Journal: British Journal of Dermatology (1998)

Hydroa vacciniforme is a troublesome and scarring photosensitivity disorder for which treatment is unsatisfactory. Dietary fish oil rich in ω‐3 polyunsaturated fatty acids reportedly increases the resistance to ultraviolet‐induced erythema and rash provocation in polymorphic light eruption. We report for the first time the response of hydroa vacciniforme to dietary fish oil. Three Caucasian boys with the condition were placed on MaxEPA, five capsules daily. Phototesting was performed at baseline and after 3 months supplementation. At baseline, low erythemal thresholds were seen to monochromated UVA at 350 and 370 nm in all three boys, while one also had a low threshold to 320 nm (UVA) and another showed a low threshold to 300 nm (UVB). Broad‐band UVA provocation challenge produced typical skin lesions in all the subjects. Following fish oil, all the boys showed reduced erythemal sensitivity to UVA and one also showed reduced sensitivity to UVB. Provocation challenge revealed a reduced response in all three children. Clinically, these changes were accompanied by pronounced improvement in one child, mild improvement in the second child, but no improvement in the third. The third boy subsequently showed good clinical response to azathioprine.
Degradation of HER2 by Cbl-Based Chimeric Ubiquitin Ligases
Authors: Xia Li, Liangliang Shen, Jing Zhang, Jin Su, Lan Shen, Xinping Liu, Hua Han, Wei Han, Libo Yao
Journal: Cancer Research (2007)

Abstract Targeting disease-causing proteins for ubiquitination and degradation by chimeric molecules represents a promising alternative therapeutic strategy in cancer. Here, several Cbl-based chimeric ubiquitin ligases were recombined to achieve effective down-regulation of HER2. These chimeric molecules consisted of the Cbl NH2-terminal tyrosine kinase binding domain, linker, and RING domain, with the Src homology 2 domain replaced with that from growth factor receptor binding protein 2 (Grb2), Grb7, p85, or Src. The chimeric proteins not only interacted with HER2 but also enhanced the down-regulation of endogenous overexpressed HER2. After the chimeric proteins were introduced into HER2-overexpressing breast cancer SK-BR-3 cells or ovarian cancer SK-OV-3 cells, they effectively promoted HER2 ubiquitination and degradation in a RING finger domain–dependent manner. Consequently, expression of these chimeric molecules led to an inhibition of colony formation, increased the proportion of cells in the G1 cycle, and suppressed tumorigenicity. Collectively, our findings suggest that the Cbl-based chimeric ubiquitin ligases designed in the present study may represent a novel approach for the targeted therapy of HER2-overexpressing cancers. [Cancer Res 2007;67(18):8716–24]
Unhelpful information about adverse drug reactions
Authors: K. Tan, K. J. Petrie, K. Faasse, M. J. Bolland, A. Grey
Journal: BMJ (2014)

<b>Kirin Tan and colleagues</b> find that information about adverse drug reactions for commonly prescribed drugs is excessive, inconsistent, often poorly presented, and contaminated by symptoms commonly experienced in daily life. They suggest how we could do better
EphA2 Reexpression Prompts Invasion of Melanoma Cells Shifting from Mesenchymal to Amoeboid-like Motility Style
Authors: Matteo Parri, Maria Letizia Taddei, Francesca Bianchini, Lido Calorini, Paola Chiarugi
Journal: Cancer Research (2009)

Eph tyrosine kinases instruct cell for a repulsive behavior, regulating cell shape, adhesion, and motility. Beside its role during embryogenesis, neurogenesis, and angiogenesis, EphA2 kinase is frequently up-regulated in tumor cells of different histotypes, including prostate, breast, colon, and lung carcinoma, as well as melanoma. Although a function in both tumor onset and metastasis has been proposed, the role played by EphA2 is still debated. Here, we showed that EphA2 reexpression in B16 murine melanoma cells, which use a defined mesenchymal invasion strategy, converts their migration style from mesenchymal to amoeboid-like, conferring a plasticity in tumor cell invasiveness. Indeed, in response to reexpression and activation of EphA2, melanoma cells activate a nonproteolytic invasive program that proceeds through the activation of cytoskeleton motility, the retraction of cell protrusions, a Rho-mediated rounding of the cell body, and squeezing among three-dimensional matrix, giving rise to successful lung and peritoneal lymph node metastases. Our results suggest that, among the redundant mechanisms operating in tumor cells to penetrate the anatomic barriers of host tissues, EphA2 plays a pivotal role in the adaptive switch in migration pattern and mechanism, defining and distinguishing tumor cell invasion strategies. Thus, targeting EphA2 might represent a future approach for the therapy of cancer dissemination.
Regional Patterns of Brain Activity in Adults With a History of Childhood-Onset Depression: Gender Differences and Clinical Variability
Authors: Anita Miller, Nathan A. Fox, Jeffrey F. Cohn, Erika E. Forbes, Joel T. Sherrill, Maria Kovacs
Journal: American Journal of Psychiatry (2002)

OBJECTIVE: The study investigated the hypothesis that EEG asymmetry scores (indicating higher right and lower left frontal brain activity) are associated with vulnerability to negative mood states and depressive disorders. Gender and clinical history variables were examined as factors that may influence the relation between EEG and depression. METHOD: EEG measures of asymmetrical alpha frequency (7.5–12.5 Hz) suppression were analyzed in 55 young adults with a documented clinical history of childhood-onset depression and 55 comparison subjects with no history of major psychopathology. EEG patterns were examined in relation to operational diagnoses of mental disorders during childhood and adulthood. RESULTS: Differences in EEG asymmetry between childhood depression probands and comparison subjects varied with gender, diagnostic history, and current symptoms. Women with childhood depression had higher right midfrontal alpha suppression, and men with childhood depression had higher left midfrontal alpha suppression, relative to comparison subjects. At all scalp sites, women showed greater alpha power than men. Probands with a bipolar spectrum course had the most extreme midfrontal asymmetry. Frontal asymmetry was more extreme in probands with current depressive symptoms than in those without current symptoms. CONCLUSIONS: Regional brain activity is influenced by gender and variability in clinical course. The findings have implications for investigating brain correlates of mood disorder and may help to develop more refined phenotypes.
Long-term follow-up after bronchoscopic lung volume reduction in patients with emphysema
Authors: Federico Venuta, Marco Anile, Daniele Diso, Carolina Carillo, Tiziano De Giacomo, Antonio D'Andrilli, Francesco Fraioli, Erino A. Rendina, Giorgio F. Coloni
Journal: European Respiratory Journal (2011)

Bronchoscopic lung volume reduction (BLVR) is a novel emphysema therapy. We evaluated long-term outcome in patients with heterogeneous emphysema undergoing BLVR with one-way valves. 40 patients undergoing unilateral BLVR entered our study. Pre-operative mean forced expiratory volume in 1 s (FEV<sub>1</sub>) was 0.88 L·s<sup>−1</sup> (23%), total lung capacity was 7.45 L (121%), intrathoracic gas volume was 6 L (174%), residual volume (RV) was 5.2 L (232%), and the 6-min walk test (6MWT) was 286 m. All patients required supplemental oxygen; the Medical Research Council (MRC) dyspnoea score was 3.9. High-resolution computed tomography (HRCT) results were reviewed to assess the presence of interlobar fissures. 33 patients had a follow-up of &gt;12 months (median 32 months). 37.5% of the patients had visible interlobar fissures. 40% of the patients died during follow-up. Three patients were transplanted and one underwent lung volume reduction surgery. Supplemental oxygen, FEV<sub>1</sub>, RV, 6MWT and MRC score showed a statistically significant improvement (p≤0.0001, p=0.004, p=0.03, p=0.003 and p&lt;0.0001, respectively). Patients with visible fissures had a functional advantage. BLVR is feasible and safe. Long-term sustained improvements can be achieved. HRCT-visible interlobar fissures are a favourable prognostic factor.
Dynamic Microtubules Regulate Dendritic Spine Morphology and Synaptic Plasticity
Authors: Jacek Jaworski, Lukas C. Kapitein, Susana Montenegro Gouveia, Bjorn R. Dortland, Phebe S. Wulf, Ilya Grigoriev, Paola Camera, Samantha A. Spangler, Paola Di Stefano, Jeroen Demmers, Harm Krugers, Paola Defilippi, Anna Akhmanova, Casper C. Hoogenraad
Journal: Neuron (2009)
Protection From Clinical Peripheral Sensory Neuropathy in Alström Syndrome in Contrast to Early-Onset Type 2 Diabetes
Authors: Richard B. Paisey, Rosamund M. Paisey, Mary P. Thomson, Lynne Bower, Pietro Maffei, Julian P.H. Shield, Sue Barnett, Jan D. Marshall
Journal: Diabetes Care (2008)

Alström syndrome, with type 2 diabetes, and blindness could confer a high risk of foot ulceration. Clinical testing for neuropathy in Alström syndrome and matched young-onset type 2 diabetic subjects was therefore undertaken.Fifty-eight subjects with Alström syndrome (18 insulin-resistant nondiabetic and 40 diabetic; aged 8-43 years) and 30 young-onset diabetic subjects (aged 13-35 years) were studied. Neuropathy symptom questionnaires were administered. Graded monofilament and 128-MHz tuning fork vibration perception were assessed in both feet.Neuropathic symptoms, loss of monofilament, and/or vibration perception were reported by 12 of the 30 young-onset type 2 diabetic subjects (6 had neuropathic ulceration) but none of the subjects with Alström syndrome.The striking preservation of protective foot sensation in Alström syndrome may provide a clue to the causes of differential susceptibility to neuropathy in the wider diabetic population.
The Incidence and Pathogenesis of Cardiopulmonary Deterioration after Abrupt Withdrawal of Inhaled Nitric Oxide
Authors: JEFFERY CHRISTENSON, ANNICK LAVOIE, MICHAEL O'CONNOR, SANGEETA BHORADE, ANNE POHLMAN, JESSE B. HALL
Journal: American Journal of Respiratory and Critical Care Medicine (2000)

We studied the effect of abrupt discontinuation of inhaled nitric oxide (iNO) in patients receiving this drug for treatment of acute hypoxemic respiratory failure (AHRF), in order to determine the need for continued therapy, the incidence and nature of adverse events, and the risk factors predicting these adverse events. Thirty-one patients who showed an initial increase in PaO2 of > 20 mm Hg in response to iNO underwent a discontinuation trial at 10 to 30 h after beginning iNO. Indwelling arterial and pulmonary artery catheters facilitated monitoring of hemodynamic and gas-exchange parameters. For the group, discontinuation of iNO caused a significant decrease in PaO2 , arterial and mixed venous oxygen saturation, and ratio of PaO2 to fraction of inspired oxygen (Fi O2 ). Three patterns of response were observed. Eight of 31 (25.8%) patients had minimal changes in oxygenation or hemodynamics, suggesting no need for ongoing therapy. Fifteen of 31 (48%) patients had worsened gas exchange as a predominant response. Eight of 31 patients exhibited hemodynamic collapse, defined as > 20% fall in cardiac output and/or mean arterial blood pressure. In this last subgroup, the pattern of cardiovascular changes suggested that this response arose from an acute increase in right ventricular afterload, and was not a consequence of gas-exchange abnormalities. In all cases, reinstitution of iNO promptly reversed worsened hemodynamics and gas exchange. Independent factors associated with an increased risk of cardiovascular collapse included multisystem organ failure, older age, and initial blood pressure increase in response to iNO; a smaller change in the ratio of PaO2 to Fi O2 with initiation of iNO therapy also tended to correlate with this phenomenon. We conclude that careful and monitored discontinuation of iNO in patients with AHRF will identify substantial fractions of patients who are either receiving no benefit from this therapy or who require iNO to maintain an adequate circulation and are therefore at risk for adverse outcome with transport or inadvertent discontinuation of iNO. Future trials of iNO should recognize this complication of such therapy and include assessments for it.
Predicting low disease activity and remission using early treatment response to antitumour necrosis factor therapy in patients with rheumatoid arthritis: exploratory analyses from the TEMPO trial
Authors: Jeffrey R Curtis, Shuo Yang, Lang Chen, Grace S Park, Bojena Bitman, Brian Wang, Iris Navarro-Millan, Arthur Kavanaugh
Journal: Annals of the Rheumatic Diseases (2011)

To derive and validate decision trees to categorise rheumatoid arthritis (RA) patients 12 weeks after starting etanercept with or without methotrexate into three groups: patients predicted to achieve low disease activity (LDA) at 1 year; patients predicted not to achieve LDA at 1 year and patients who needed additional time on therapy to be categorised.Data from RA patients enrolled in the TEMPO trial were analysed. Classification and regression trees were used to develop and validate decision tree models with week 12 and earlier assessments that predicted long-term LDA. LDA, defined as disease activity score in 28 joints (DAS28) ≤3.2 or clinical disease activity index ≤10.0, was measured at 52 or 48 weeks. Demographics, laboratory data and clinical data at baseline and to week 12 were analysed as predictors of response.39% (67/172) of patients receiving etanercept and 60% (115/193) of patients receiving etanercept plus methotrexate achieved LDA at week 52. For patients receiving etanercept, 53% were predicted to have LDA, 39% were predicted not to have LDA and 8% could not be categorised using DAS28 criteria at week 12. For patients receiving etanercept plus methotrexate, 63% were predicted to have LDA, 25% were predicted not to have LDA and 12% could not be categorised.Most (80-90%) patients in TEMPO initiating etanercept with or without methotrexate could be predicted within 12 weeks of starting therapy as likely to have LDA or not at week 52. However, approximately 10-20% of patients needed additional time on therapy to decide whether to continue treatment.
Increase of Plasma VEGF after Intravenous Administration of Bevacizumab Is Predicted by a Pharmacokinetic Model
Authors: Marianne O. Stefanini, Florence T. H. Wu, Feilim Mac Gabhann, Aleksander S. Popel
Journal: Cancer Research (2010)

Abstract Vascular endothelial growth factor (VEGF) is one of the most potent cytokines targeted in antiangiogenic therapies. Bevacizumab, a recombinant humanized monoclonal antibody to VEGF, is being used clinically in combination with chemotherapy for colorectal, non–small cell lung and breast cancers, and as a single agent for glioblastoma and is being tested for other types of cancer in numerous clinical trials. It has been reported that the intravenous injection of bevacizumab leads to an increase of plasma VEGF concentration in cancer patients. The mechanism responsible for this counterintuitive increase has not been elucidated, although several hypotheses have been proposed. We use a multiscale systems biology approach to address this problem. We have constructed a whole-body pharmacokinetic model comprising three compartments: blood, normal tissue, and tumor tissue. Molecular interactions among VEGF-A family members, their major receptors, the extracellular matrix, and an anti-VEGF ligand are considered for each compartment. Diffusible molecules extravasate, intravasate, are removed from the healthy tissue through the lymphatics, and are cleared from the blood. Cancer Res; 70(23); 9886–94. ©2010 AACR.
The clinical course of cirrhosis: The importance of multistate models and competing risks analysis
Authors: Peter Jepsen, Hendrik Vilstrup, Per Kragh Andersen
Journal: Hepatology (2014)

Multistate models are models of disease progression that, for a patient group, define multiple outcome events, each of which may affect the time to develop another outcome event. Multistate models are highly relevant for studies of patients with cirrhosis; both the classical perception of cirrhosis as either compensated or decompensated and the recent, more complex models of cirrhosis progression are multistate models. Therefore, researchers who conduct clinical studies of patients with cirrhosis must realize that most of their research questions assume a multistate disease model. Failure to do so can result in severely biased results and bad clinical decisions. The analyses that can be used to study disease progression in a multistate disease model may be called competing risks analysis , named after the competing risks disease model, which is the simplest multistate disease model. In this review article, we introduce multistate disease models and competing risks analysis and explain why the standard armamentarium of Kaplan‐Meier survival estimates and Cox regression sometimes gives bad answers to good questions. We also use real data to answer typical research questions about the course of cirrhosis and illustrate biases resulting from inadequate methods. Finally, we suggest statistical software packages that are helpful and accessible to the clinician‐researcher. (H epatology 2015;62:292‐302)
Charting the landscape of priority problems in psychiatry, part 1: classification and diagnosis
Authors: Klaas E Stephan, Dominik R Bach, Paul C Fletcher, Jonathan Flint, Michael J Frank, Karl J Friston, Andreas Heinz, Quentin J M Huys, Michael J Owen, Elisabeth B Binder, Peter Dayan, Eve C Johnstone, Andreas Meyer-Lindenberg, P Read Montague, Ulrich Schnyder, Xiao-Jing Wang, Michael Breakspear
Journal: The Lancet Psychiatry (2015)
Baroreflex sensitivity and electrophysiological correlates in patients after acute myocardial infarction.
Authors: T G Farrell, V Paul, T R Cripps, M Malik, E D Bennett, D Ward, A J Camm
Journal: Circulation (1991)

Several studies have identified transient disturbances of autonomic function during the acute and recovery phases of myocardial infarction, and it has recently been suggested that survivors of acute myocardial infarction with depressed vagal tone may be at increased risk of sudden or arrhythmic death.To investigate this hypothesis, parasympathetic function was assessed by arterial baroreflex sensitivity (BRS) testing (using the phenylephrine method) and by heart rate variability (HRV) analysis from 24-hour Holter recording in 68 patients at day 7-10 after infarction. The relation between autonomic tone and markers of arrhythmic propensity, including programmed ventricular stimulation (PVS) and late potentials in addition to other clinical variables, was examined. BRS for the whole group was 7.0 +/- 4.7 msec/mm Hg and was inversely correlated with age (r = 0.53, p less than 0.001) but not with left ventricular ejection fraction (r = 0.035, p = NS). In those patients in whom sustained monomorphic ventricular tachycardia (SMVT) was induced, BRS was significantly reduced (p = 0.001) as was HRV (p = 0.007) and left ventricular ejection fraction (p = 0.022). The strongest association between any variable (including HRV, BRS, late potentials, left ventricular ejection fraction, exercise testing, Q waves, and infarct site) and the induction of sustained monomorphic ventricular tachycardia was depressed BRS with a relative risk of 36.28 (95% confidence interval, 5-266).This study confirms that depressed BRS identifies a subgroup at high risk for arrhythmic events after myocardial infarction and that programmed ventricular stimulation may be safely limited to this group without any loss of predictive accuracy.