tbuckley/cabot-search huggingface dataset:
Late-breaking abstract: Elevated cardiovascular risk as measured by QRISK2 score in patients hospitalized for acute COPD exacerbation versus stable COPD outpatients
Authors: Elisa Pagliaroli, Divya Mohan, Vijay Padmanaban, Sarah Elkin, Paolo Palange, Michael Polkey
Journal: European Respiratory Journal (2014)

Introduction:  Cardiovascular (CV) disease is the second commonest cause of death in COPD, and exacerbations increase risk of a CV event. We wished to evaluate the QRISK2 score as a predictor of the CV risk in patients with acute COPD exacerbations versus a stable COPD cohort.   Methods:  We studied 180 patients hospitalized for COPD exacerbation retrospectively and 61 COPD outpatients prospectively, exacerbation free for >4 weeks. Hospitalized patients were split according to the presence (Group 1) or the absence (Group 2) of previous CV events. Stable patients formed Group 3.We recorded medical history, CRP, lipids, BMI and spirometry. BNP levels were available for only 39 patients. Mann-Whitney and ANOVA tests were used for statistics.   Results:  Relative risk (RR), or absolute risk (AR)/theoretical risk ratio, was higher in the hospitalized group (p  In the hospitalized patients AR correlated with BNP (r= 0.44, p=0.006), FEV 1 %pred (r= 0.40, p 1 /FVC (r=0.24, p=0.02), but not with CRP. No correlation was present in Group 3.   Conclusion:  Patients hospitalized for COPD exacerbations appear to have an higher CV risk at admission than stable COPD outpatients. For this, QRISK2 score could be a useful tool to stratify risk and guide treatment.
Neuropsychological Measures of Attention and Impulse Control among 8-Year-Old Children Exposed Prenatally to Organochlorines
Authors: Sharon K. Sagiv, Sally W. Thurston, David C. Bellinger, Larisa M. Altshul, Susan A. Korrick
Journal: Environmental Health Perspectives (2012)

We previously reported associations between organochlorines and behaviors related to attention deficit hyperactivity disorder among boys and girls at 8 years of age using a teacher's rating scale for a birth cohort in New Bedford, Massachusetts (USA).Our goal was to corroborate these findings using neuropsychological measures of inattentive and impulsive behaviors.We investigated the association between cord serum polychlorinated biphenyls (PCBs) and p,p'-dichlorodiphenyl dichloroethylene (p,p'-DDE) and attention and impulse control using a Continuous Performance Test (CPT) and components of the Wechsler Intelligence Scale for Children, 3rd edition (WISC-III). Participants came from a prospective cohort of children born during 1993-1998 to mothers residing near a PCB-contaminated harbor in New Bedford. Median (range) cord serum levels for the sum of four prevalent PCBs [congeners 118, 138, 153, and 180 (ΣPCB4)] and p,p'-DDE were 0.19 (0.01-2.59) and 0.31 (0-14.93) ng/g serum, respectively.We detected associations between PCBs and neuropsychological deficits for 578 and 584 children with CPT and WISC-III measures, respectively, but only among boys. For example, boys with higher exposure to ΣPCB4 had a higher rate of CPT errors of omission [rate ratio for the exposure interquartile range (IQR) = 1.12; 95% confidence interval (CI): 0.98, 1.27] and slower WISC-III Processing Speed (change in score for the IQR = -2.0; 95% CI: -3.5, -0.4). Weaker associations were found for p,p'-DDE. For girls, associations were in the opposite direction for the CPT and null for the WISC-III.These results support an association between organochlorines (mainly PCBs) and neuropsychological measures of attention among boys only. Sex-specific effects should be considered in studies of organochlorines and neurodevelopment.
Anthracofibrosis attributed to mixed mineral dust exposure: report of three cases
Authors: J-M Naccache, I Monnet, H Nunes, M-A Billon-Galland, J-C Pairon, F Guillon, D Valeyre
Journal: Thorax (2008)

Anthracofibrosis, defined as bronchial luminal narrowing with black pigmentation of the overlying mucosa, has been attributed to tuberculosis. Three patients with anthracofibrosis without mycobacterial infection are described who had previous occupational exposure to mixed dusts. CT scans showed calcified hilar lymph nodes in two patients. Surgical biopsy in one patient and autopsy in another revealed fibrotic lymph nodes with black pigmentation. Mineralogical analysis by transmission electron microscopy of pulmonary, hilar and/or bronchial samples found high levels of particle retention, raised percentages of free crystalline silica and mica in two patients, and free crystalline silica, kaolin and other silicates in the third. No evidence of any other contributory factor was found, suggesting that mixed mineral dust was the most probable cause. These observations suggest that exposure to mixed mineral dust should be added to the aetiology of anthracofibrosis.
Upper body contribution to high intensity cycle ergometer exercise: implications for blood lactate measurements and power profiles
Authors: J S Baker
Journal: British Journal of Sports Medicine (2004)

If you have a burning desire to respond to a paper published in BJSM, why not make use of our ''rapid response'' option?Log onto our website (www.bjsportmed.com), find the paper that interests you, and send your response via email by clicking on the ''eLetters'' option in the box at the top right hand corner.Providing it isn't libellous or obscene, it will be posted within seven days.You can retrieve it by clicking on ''read eLetters'' on our homepage. Mandatory wearing of helmets for elite cyclists: new perspectives in prevention of head injuriesCycling related injuries, especially those to the head, are common causes of morbidity, death, and disability and could largely be prevented by the proper use of hard shell helmets. 1 2 Unfortunately, obvious evidence is often not acknowledged, and the use of such a valuable preventive measure has been too long ignored.Media coverage of elite competitions, showing most athletes racing without helmets, has unfavourably influenced amateur and young cyclists for a long time.However, owing to the progressive increase in severe and fatal injuries, especially involving elite cyclists, and the evidence that the outcome of most of these tragedies might have been prevented, 1 2 the International Cycling Union announced that, from 5 May 2003, it is mandatory to wear a hard shell helmet in elite men's events for classes 4 and above.This decision was taken in agreement with the Professional Riders Association, who supported the initiative despite some internal differences of opinion.Images transmitted world wide during the 2003 Tour de France, a sporting event second in popularity only to the Olympics, are encouraging, showing all athletes wearing helmets throughout most of the race.This is a valuable message for both amateur cyclists and adolescents, as awareness is often more productive than restrictive measures.In addition, individual persuasion to wear helmets does not have the side effect of reducing the incentive to do cycling.Less cycling, in reaction to restrictive legislation, may counterbalance the beneficial effects on head injury prevention, as regular recreational aerobic activity, such as cycling, has manifest benefits on health, preventing the development of chronic disorders, including atherosclerosis, diabetes, osteoporosis, obesity, depression, and cancer.
Evolving Concepts of Cardiac Valve Dynamics
Authors: Frederick J. Schoen
Journal: Circulation (2008)

Considerable progress has been made in recent years toward elucidating a conceptual framework that integrates the dynamic functional structure, mechanical properties, and pathobiological behavior of the cardiac valves. This communication reviews the evolving paradigm of a continuum of heart valve structure, function, and pathobiology and explores its implications. Specifically, we discuss (1) the interactions of valve biology and biomechanics (eg, correlations of function with structure at the cell, tissue, and organ levels and mechanical considerations, development, endothelial cell and interstitial cell biology, extracellular matrix biology, homeostasis, and adaptation to environmental change); (2) mechanisms of disease (eg, valve cell and matrix pathobiology in congenital anomalies, aortic valve calcification, and mitral valve prolapse); (3) considerations in replacement and repair (eg, cell/matrix biology of tissue valve substitutes and their degeneration and durability of repairs); and (4) the potential for tissue engineering approaches to therapeutic regeneration of the cardiac valves. Opportunities for research and clinical translation are highlighted.
Knob-independent cytoadherence of Plasmodium falciparum to the leukocyte differentiation antigen CD36.
Authors: B A Biggs, L Goozé, K Wycherley, D Wilkinson, A W Boyd, K P Forsyth, L Edelman, G V Brown, J H Leech
Journal: The Journal of Experimental Medicine (1990)

The survival of Plasmodium falciparum-infected erythrocytes is enhanced by the sequestration of mature trophozoites and schizonts from the peripheral circulation. Cytoadherence of infected erythrocytes in vivo is associated with the presence of knobs on the erythrocyte surface, but we and others have shown recently that cytoadherence to C32 melanoma cells may occur in vitro in the absence of knobs. We show here that a knobless clone of P. falciparum adheres to the leukocyte differentiation antigen, CD36, suggesting that binding to CD36 is independent of the presence of knobs on the surface of the infected erythrocyte. This clone showed little cytoadherence to immobilized thrombospondin or to endothelial cells expressing the intercellular adhesion molecule 1. Furthermore, an Mr approximately 300-kD trypsin-sensitive protein doublet was immunoprecipitated from knobless trophozoite-infected erythrocytes. Finding a P. falciparum erythrocyte membrane protein 1 (PfEMP1)-like molecule on these infected erythrocytes is consistent with a role for PfEMP1 in cytoadherence to CD36 and C32 melanoma cells.
Molecular Pathways: The Role of Primary Cilia in Cancer Progression and Therapeutics with a Focus on Hedgehog Signaling
Authors: Nadia B. Hassounah, Thomas A. Bunch, Kimberly M. McDermott
Journal: Clinical Cancer Research (2012)

Abstract Abnormal Hedgehog (Hh) pathway activity has been reported in many cancers, including basal cell carcinomas, medulloblastomas, rhabdomyosarcomas, glioblastomas, and breast and prostate cancers. For this reason, the Hh pathway is a flourishing area for development of anticancer drugs such as Hh ligand antagonists (e.g., 5E1 and robotnikinin), Smo inhibitors (e.g., GDC-0449 and IPI-926), and Gli transcriptional activity inhibitors (e.g., GANT58 and GANT61). It is now clear that primary cilia are required for activation of the Hh pathway in normal vertebrate cells. It is in the primary cilium that both positive and negative effectors of the Hh pathway are processed by posttranslational modifications. In many cancers, preliminary results suggest that primary cilia are lost. As drugs that inhibit different steps of the Hh pathway are developed, it will be important to consider how these drugs will function in the context of primary cilia in the tumor environment. Here, we discuss why some of the Hh inhibitors may be ineffective if primary cilia are lost on cancer cells. Understanding the relationships between clinical inhibitors of the Hh pathway and the presence or absence of primary cilia may turn out to be critical for targeting these therapeutics to the correct population of patients and improving their efficacy. Further work is needed in this area to maximize the potential of these exciting therapeutic targets. Clin Cancer Res; 18(9); 2429–35. ©2012 AACR.
Distinct ErbB-2–Coupled Signaling Pathways Promote Mammary Tumors with Unique Pathologic and Transcriptional Profiles
Authors: Babette Schade, Sonya H.L. Lam, Daniela Cernea, Virginie Sanguin-Gendreau, Robert D. Cardiff, Boonim L. Jung, Michael Hallett, William J. Muller
Journal: Cancer Research (2007)

Abstract ErbB-2 overexpression and amplification occurs in 15% to 30% of human invasive breast carcinomas associated with poor clinical prognosis. Previously, we have shown that four ErbB-2/Neu tyrosine-autophosphorylation sites within the cytoplasmic tail of the receptor recruit distinct adaptor proteins and are sufficient to mediate transforming signals in vitro. Two of these sites, representing the growth factor receptor binding protein 2 (Grb2; Neu-YB) and the Src homology and collagen (Shc; Neu-YD) binding sites, can induce mammary tumorigenesis and metastasis. Here, we show that transgenic mice bearing the two other ErbB-2 autophosphorylation sites (Neu-YC and Neu-YE) develop metastatic mammary tumors. A detailed comparison of biological profiles among all Neu mutant mouse models revealed that Neu-YC, Neu-YD, and Neu-YE mammary tumors shared similar pathologic and transcriptional features. By contrast, the Neu-YB mouse model displayed a unique pathology with a high metastatic potential that correlates with a distinct transcriptional profile, including genes that promote malignant tumor progression such as metalloproteinases and chemokines. Furthermore, Neu-YB tumor epithelial cells showed abundant intracellular protein level of the chemokine CXCL12/SDF-1α, which may reflect the aggressive nature of this Neu mutant mouse model. Taken together, these findings indicate that activation of distinct Neu-coupled signaling pathways has an important impact on the biological behavior of Neu-induced tumors. [Cancer Res 2007;67(16):7579–88]
Maternal Hyperglycemia During Pregnancy Predicts Adiposity of the Offspring
Authors: Ai Kubo, Assiamira Ferrara, Gayle C. Windham, Louise C. Greenspan, Julianna Deardorff, Robert A. Hiatt, Charles P. Quesenberry, Cecile Laurent, Anousheh S. Mirabedi, Lawrence H. Kushi
Journal: Diabetes Care (2014)

To investigate associations between maternal pregnancy hyperglycemia, gestational diabetes mellitus (GDM), and offspring adiposity.We evaluated these associations in a longitudinal study of 421 mother-daughter pairs at Kaiser Permanente Northern California. Maternal pregnancy glucose values were obtained from maternal medical records. Outcomes included three measures of girls' adiposity, measured annually: (1) ≥85th age-specific percentile for BMI; (2) percent body fat (%BF); and (3) waist-to-height ratio (WHR).Adjusting for maternal age at delivery, race/ethnicity, pregravid BMI, girl's age, and girl's age at onset of puberty, having a mother with GDM increased a girl's risk of having a BMI ≥85th percentile or having %BF or WHR in the highest quartile (Q4), compared with those in the lowest quintile of blood glucose (odds ratio [OR] 3.56 [95% CI 1.28-9.92]; OR 3.13 [95% CI 1.08-9.09]; and OR 2.80 [95% CI 1.00-7.84], respectively). There was a significant interaction between the presence of GDM and pregravid BMI; girls whose mothers had both risk factors had the highest odds of having a BMI ≥85th percentile (OR 5.56 [95%CI 1.70-18.2]; Q4 %BF, OR 6.04 [95% CI 1.76-20.7]; and Q4 WHR, OR 3.60 [95% CI 1.35-9.58]). Similar, although weaker, associations were found in the association between hyperglycemia and offspring adiposity.Girls who were exposed to maternal GDM or hyperglycemia in utero are at higher risk of childhood adiposity; risk increases if the mother is overweight or obese. Screening and intervention for this high-risk group is warranted to slow the intergenerational transmission of obesity and its sequelae.
Mid-Term Comparative Follow-Up After Aortic Valve Replacement with Carpentier-Edwards and Pericarbon Pericardial Prostheses
Authors: T. Le Tourneau, C. Savoye, E. P. McFadden, D. Grandmougin, H.-F. Carton, J.-L. Hennequin, A. Dubar, G. Fayad, H. Warembourg
Journal: Circulation (1999)

The first generation of pericardial valves had a high rate of premature deterioration. The aim of this study was to compare the outcome after aortic valve replacement with second generation pericardial prostheses (Pericarbon and Carpentier-Edwards).Between 1987 and 1994, 162 patients underwent aortic valve replacement with either a Pericarbon (n=81, 69+/-11 years) or a Carpentier-Edwards (n=81, 70+/-11 years) pericardial prosthesis. Mean follow-up was 4.4+/-2.7 years for Pericarbon and 4.8+/-2.4 years for Carpentier-Edwards valves (P=0. 27), giving a total follow-up of 745 patient-years. Thirty-day mortality and 5-year actuarial survival were, respectively, 6.2% and 63.2+/-5.7% in the Pericarbon group and 6.2% and 63.5+/-5.6% in the Carpentier-Edwards group. At 8 years, freedom from (and linearized rates per patient-year) thromboembolism, structural failure, and all valve-related events were, respectively, 91.8+/-3.6% (1.4%), 76. 9+/-8.7% (2.5%), and 58.4+/-9.3% (5.6%) in the Pericarbon group and 94.4+/-2.7% (1%), 100% (0%, P<0.01), and 88.8+/-3.7% (2%, P<0.05) in the Carpentier-Edwards group. There were 9 (11.1%) Pericarbon structural failures related predominantly to severe calcification and stenosis. The actual reoperation rate was 7.4% (1.6% per patient-year) in the Pericarbon group for fibrocalcific degeneration (n=3), periprosthetic leak (n=1), endocarditis (n=1), and aortic dissection (n=1). There was neither structural valve failure nor valve reoperation in the Carpentier-Edwards group. Echocardiographic review of 70 patients from 85 survivors (82.3%) found 4 additional Pericarbon valves with signs of early structural failure but no Carpentier-Edwards valve with such changes.Eight years after aortic valve replacement, Pericarbon pericardial prostheses compared unfavorably with Carpentier-Edwards pericardial prostheses, with a high incidence of structural valve failure and reoperation.
Sodium and the Cachexia and Hypophagia of Tumor Growth
Authors: S. D. Morrison
Journal: JNCI Journal of the National Cancer Institute (1974)

The possibility that salt depletion generated by tumor growth is responsible for the depression of food intake induced by tumor growth was reexamined by three different methods of salt supplement administration during growth of Walker carcinoma 256. The effect of the salt supplement on changes in energy exchange and water exchange of the host was also measured. Salt supplement increased water intake in normal and tumor-bearing rats. It increased water retention and body-weight gain in tumorbearing rats, and these animals retained most of the sodium administered. There was no systematic effect on food intake, on energy expenditure, or on the motor activity compartment of energy expenditure in normal or tumorbearing rats.
Age-Dependent Changes in Health Status in the Childhood Cancer Survivor Cohort
Authors: Melissa M. Hudson, Kevin C. Oeffinger, Kendra Jones, Tara M. Brinkman, Kevin R. Krull, Daniel A. Mulrooney, Ann Mertens, Sharon M. Castellino, Jacqueline Casillas, James G. Gurney, Paul C. Nathan, Wendy Leisenring, Leslie L. Robison, Kirsten K. Ness
Journal: Journal of Clinical Oncology (2014)

To compare age-dependent changes in health status among childhood cancer survivors and a sibling cohort.Adult survivors of childhood cancer and siblings, all participants of the Childhood Cancer Survivor Study, completed three surveys assessing health status. At each of three time points, participants were classified as having poor outcomes in general health, mental health, function, or daily activities if they indicated moderate to extreme impairment. Generalized linear mixed models were used to compare survivors with siblings for each outcome as a function of age and to identify host- and treatment-related factors associated with age-dependent worsening health status.Adverse health status outcomes were more frequent among survivors than siblings, with evidence of a steeper trajectory of age-dependent change among female survivors with impairment in at least one health status domain (P = .01). In adjusted models, survivors were more likely than siblings to report poor general health (prevalence ratio [PR], 2.37; 95% CI, 2.09 to 2.68), adverse mental health (PR, 1.66; 95% CI, 1.52 to 1.80), functional impairment (PR, 4.53; 95% CI, 3.91 to 5.24), activity limitations (PR, 2.38; 95% CI, 2.12 to 2.67), and an adverse health status outcome in any domain (PR, 2.10; 95% CI, 1.97 to 2.23). Cancer treatment and health behaviors influence the magnitude of differences by age groups. Chronic conditions were associated with adverse health status outcomes across organ systems.The prevalence of poor health status is higher among survivors than siblings, increases rapidly with age, particularly among female participants, and is related to an increasing burden of chronic health conditions.
The BMJ is wrong: doctor assisted dying would overmedicalise death
Authors: M. McCartney
Journal: BMJ (2014)

The BMJ has decided to support the Assisted Dying Bill.1 This is a mistake.

Medicine wields at once too much power and too little. We are rather impotent, for example, around social inequalities.2 Despite evidence that financial gradients make health worse, we lack the clout to influence government policy to tackle them. Yet, on the flipside, medical power can be exerted firmly in places where a much lighter touch would have been far better.

We have already overmedicalised birth, such that many women have had interventions that they or their child could not benefit from and that only disadvantaged them.3 We have told healthy people that they need to be screened or have …
The Pattern of Amino Acid Replacements in α/β-Barrels
Authors: Antony M. Dean, Claudia Neuhauser, Elise Grenier, G. Brian Golding
Journal: Molecular Biology and Evolution (2002)

The determinants of site-to-site variability in the rate of amino acid replacement in alpha/beta-barrel enzyme structures are investigated. Of 125 available alpha/beta-barrel structures, only 25 meet a variety of phylogenetic and statistical criteria necessary to ensure sufficient data for reliable analysis. These 25 enzyme structures (from a wide variety of taxa with diverse lifestyles in diverse habitats) differ greatly in size, number, and topology of domains in addition to the alpha/beta-barrel, quaternary structure, metabolic role, reaction catalyzed, presence of prosthetic groups, regulatory mechanisms, use of cofactors, and catalytic mechanisms. Yet, with the exception of ribulose-1,5-bisphosphate carboxylase, all structures have similar frequency distributions of amino acid replacement rates. Hence, site-specific variability in rates of evolution is largely independent of differences in biology, biochemistry, and molecular structure. A correlation between site-specific rate variation and (1) distance from the active site, (2) solvent accessibility, and (3) treating glycines in unusual main-chain conformations as a separate class, explains approximately half the causal variation. Secondary structure exerts little influence on the pattern and distribution of replacements. Additional domains and subunits, side-chain hydrogen bonds, unusual side-chain rotamers, nonplanar peptide bonds, strained main-chain conformations, and buried hydrophilic-charged residues contribute little to variability among sites because they are rare. Nonlinear models do not improve the fits. In several enzymes, deviations from the typical pattern of replacements suggest the possible action of natural selection. A statistical analysis shows that, in all cases, much of the remaining unexplained variation is not attributable to chance and that other, as yet unidentified, causal relations must exist.
Describing right ventricular function
Authors: Anton Vonk-Noordegraaf, Nico Westerhof
Journal: European Respiratory Journal (2013)

In pulmonary hypertension and other conditions, such as acute respiratory distress syndrome and left heart failure, right ventricular dysfunction is a prognostic determinant. Therefore, functional parameters pertaining to the right heart alone, i.e. independent of its loading conditions, should be used to quantify right ventricular disease progression and the results of treatment. Two methods to quantitatively describe right ventricular function are reviewed, the pressure–volume relationship and the pump function graph; examples of each method are given. How to estimate wall stress and how to describe diastolic ventricular properties are also discussed.