tbuckley/cabot-search huggingface dataset:
P161 Global prevalence of chronic pulmonary aspergillosis (CPA) following pulmonary tuberculosis (PTB)
Authors: D. W. Denning, A. Pleuvry, D. C. Cole
Journal: Thorax (2010)

<h3>Background</h3> One of the sequelae of PTB is the development of CPA, with or without an aspergilloma. We estimated the global 5 year period prevalence of CPA. <h3>Methods</h3> Estimation of the number of cases of PTB and deaths was made by the WHO. The frequency of pulmonary cavities after PTB treatment varied from 8% (Vietnam) to 35% (Taiwan), with rates in South Africa and US of 21–23% and Brazil of 30%; we used a rate of 22% except in Europe (12%). CPA (pulmonary cavity(s) + positive Aspergillus serology) annual incidence was estimated from PTB cases with cavities (22%) and without cavities (2%). Annual mortality following PTB varies from 5% (Denmark) to 15% (Uzbekistan) and is higher in HIV infected patients (26%) and those with MDR PTB (12%). We calculated the 5 year prevalence using annual attrition rates of 10–25%. <h3>Results</h3> In 2007, WHO estimated 7.7M PTB cases globally, with 77.1% 1-year survival. We estimate that 372 385 patients worldwide developed CPA following PTB in 2007, distributed 11 420 (Europe), 12 610 (Americas), 98 551 (Africa), 20 615 (E. Mediterranean), 83 815 (W. Pacific) and 145 372 (SE Asia). In the UK, the annual new CPA caseload from PTB is estimated to be 118 cases with an estimated 5 year period prevalence of 433 cases. 5 year estimated CPA prevalence using median estimates above was: Sensitivity analyses using 10% or 30% rates of cavity formation after PTB and CPA rates in those without cavities (1% or 4%) alter the estimates from a low global 5 year prevalence rate of 546 844 to a high of 1 786 421 patients living with CPA, at a 15% attrition rate. <h3>Conclusions</h3> CPA following PTB is a significant public health problem in Africa, W. Pacific and SE Asia. A lack of contemporary research limits the precision of estimates regionally and globally.
Phase III study of ACVBP versus ACVBP plus rituximab for patients with localized low-risk diffuse large B-cell lymphoma (LNH03-1B)
Authors: N. Ketterer, B. Coiffier, C. Thieblemont, C. Fermé, J. Brière, O. Casasnovas, S. Bologna, B. Christian, T. Connerotte, C. Récher, D. Bordessoule, C. Fruchart, R. Delarue, C. Bonnet, F. Morschhauser, B. Anglaret, C. Soussain, B. Fabiani, H. Tilly, C. Haioun
Journal: Annals of Oncology (2012)
Myelomatous Involvement Of The Central Nervous System: Mayo Clinic Experience
Authors: Jonas Paludo, Utkarsh Painuly, Shaji Kumar, Francis Buadi, Suzanne R Hayman, Martha Q. Lacy, Angela Dispenzieri, John A. Lust, David Dingli, Arleigh McCurdy, Stephen J. Russell, Nelson Leung, Steven R Zeldenrust, Vincent Rajkumar, Morie A Gertz, Robert Kyle, Prashant Kapoor
Journal: Blood (2013)
The debate over digital technology and young people
Authors: Vaughan Bell, Dorothy V M Bishop, Andrew K Przybylski
Journal: BMJ (2015)

Needs less shock and more substance

Through appearances, interviews, and a recent book1 Susan Greenfield, a senior research fellow at Lincoln College, Oxford, has promoted the idea that internet use and computer games can have harmful effects on the brain, emotions, and behaviour, and she draws a parallel between the effects of digital technology and climate change. Despite repeated calls for her to publish these claims in the peer reviewed scientific literature, where clinical researchers can check how well they are supported by evidence, this has not happened, and the claims have largely been aired in the media. As scientists working in mental health, developmental neuropsychology, and the psychological impact of digital technology, we are concerned that Greenfield’s claims are not based on a fair scientific appraisal of the evidence, often confuse correlation for causation, give undue weight to anecdote and poor quality studies, and are misleading to parents and the public at large.

Greenfield claims that social networking sites could negatively affect social interaction, interpersonal empathy, and personal identity.1 However, the bulk of research does not …
How common are myeloproliferative neoplasms? A systematic review and meta‐analysis
Authors: Glen J. Titmarsh, Andrew S. Duncombe, Mary Frances McMullin, Michael O'Rorke, Ruben A Mesa, Frank De Vocht, Sarah Horan, Lin Fritschi, Mike Clarke, Lesley A. Anderson
Journal: American Journal of Hematology (2015)
Microbial aetiology of healthcare associated pneumonia in Spain: a prospective, multicentre, case–control study
Authors: Eva Polverino, Antoni Torres, Rosario Menendez, Catia Cillóniz, Jose Manuel Valles, Alberto Capelastegui, M Angeles Marcos, Inmaculada Alfageme, Rafael Zalacain, Jordi Almirall, Luis Molinos, Salvador Bello, Felipe Rodríguez, Josep Blanquer, Antonio Dorado, Noelia Llevat, Jordi Rello
Journal: Thorax (2013)

<h3>Introduction</h3> Healthcare-associated pneumonia (HCAP) is actually considered a subgroup of hospital-acquired pneumonia due to the reported high risk of multidrug-resistant pathogens in the USA. Therefore, current American Thoracic Society/Infectious Diseases Society of America guidelines suggest a nosocomial antibiotic treatment for HCAP. Unfortunately, the scientific evidence supporting this is contradictory. <h3>Methods</h3> We conducted a prospective multicentre case–control study in Spain, comparing clinical presentation, outcomes and microbial aetiology of HCAP and community-acquired pneumonia (CAP) patients matched by age (±10 years), gender and period of admission (±10 weeks). <h3>Results</h3> 476 patients (238 cases, 238 controls) were recruited for 2 years from June 2008. HCAP cases showed significantly more comorbidities (including dysphagia), higher frequency of previous antibiotic use in the preceding month, higher pneumonia severity score and worse clinical status (Charslon and Barthel scores). While microbial aetiology did not differ between the two groups (HCAP and CAP: <i>Streptococcus</i><i>pneumoniae</i>: 51% vs 55%; viruses: 22% vs 12%; <i>Legionella</i>: 4% vs 9%; Gram-negative bacilli: 5% vs 4%; <i>Pseudomonas aeruginosa</i>: 4% vs 1%), HCAP patients showed worse mortality rates (1-month: HCAP, 12%; CAP 5%; 1-year: HCAP, 24%; CAP, 9%), length of hospital stay (9 vs 7 days), 1-month treatment failure (5.5% vs 1.5%) and readmission rate (18% vs 11%) (p&lt;0.05, each). <h3>Conclusions</h3> Despite a similar clinical presentation, HCAP was more severe due to patients’ conditions (comorbidities) and showed worse clinical outcomes. Microbial aetiology of HCAP did not differ from CAP indicating that it is not related to increased mortality and in Spain most HCAP patients do not need nosocomial antibiotic coverage.
Effectiveness of Diabetic Therapeutic Footwear in Preventing Reulceration
Authors: Matthew L. Maciejewski, Gayle E. Reiber, Douglas G. Smith, Carolyn Wallace, Shane Hayes, Edward J. Boyko
Journal: Diabetes Care (2004)

OBJECTIVE—To review the evidence for the effectiveness of therapeutic footwear in preventing foot reulceration in individuals with diabetes and foot risk factors. RESEARCH DESIGN AND METHODS—We conducted a structured literature review based on a Medline search for studies of therapeutic footwear that examined prevention of reulceration. Nine published articles were identified. Characteristics of the study population, components of the intervention, and level of adherence were evaluated. U.S. Preventive Services Task Force criteria for evaluating research were applied to rate each study on study design and internal validity. RESULTS—Risk ratios in all studies assessing the association between therapeutic footwear and reulceration were below 1.0, suggesting some protective footwear benefit. However, in the most rigorous experimental study, no statistically significant benefit was observed between control patients wearing their own footwear and intervention patients wearing study footwear. Annual reulceration in these studies’ control groups ranged from 8.4 to 59.3%. In patients with severe foot deformity or prior toe or ray amputation, observational studies suggested a significant protective benefit from therapeutic footwear. CONCLUSIONS—Therapeutic footwear has been used for decades as one of many strategies to prevent reulceration in patients with diabetes and foot risk factors. The findings of several studies reporting statistically significant protective effects from therapeutic footwear may have been influenced by several design issues. When considering the appropriateness of therapeutic footwear recommendations for moderate-risk patients, clinicians and patients should jointly explore individual strategies to decrease events that lead to foot ulcers.
Diagnosing TB infection in children: analysis of discordances using in vitro tests and the tuberculin skin test
Authors: N. Altet-Gomez, M. De Souza-Galvao, I. Latorre, C. Mila, M. A. Jimenez, J. Solsona, A. Cantos, J. J. Zamora, J. Ruiz-Manzano, V. Ausina, J. Dominguez
Journal: European Respiratory Journal (2010)

The aim of the present study was to compare the performance of the interferon (IFN)-γ tests (QuantiFERON®-TB Gold In-Tube (QFT-G-IT) and T-SPOT®.<i>TB</i>) with the tuberculin skin test (TST) in diagnosing tuberculosis (TB) infection in children, and to analyse discordant results. This was a prospective study including 98 children from contact-tracing studies and 68 children with TST indurations ≥5 mm recruited during public health screenings. Positive IFN-γ tests results were associated with risk of exposure (p&lt;0.0001). T-SPOT.<i>TB</i> was positive in 11 (78.6%) out of 14 cases with active TB and QFT-G-IT in nine (64.3%) out of 14 cases. Sensitised T-cells against <i>Mycobacterium avium</i> were detected in six out of 12 children not vaccinated with bacille Calmette-Guérin (BCG), a TST induration 5–9 mm in diameter and both IFN-γ tests negative. In concordant IFN-γ tests results, a positive correlation was found (p = 0.0001) between the number of responding cells and the amount of IFN-γ released. However, in discordant IFN-γ tests results this correlation was negative (p = 0.371): an increase in the number of spot-forming cells correlated with a decrease in the amount of IFN-γ released. The use of IFN-γ tests is helpful for the diagnosis of TB infection, avoiding cross-reactions with BCG immunisation and nontuberculous mycobacterial infections. The analysis of highly discordant results requires further investigation to elucidate possible clinical implications.
THE EFFECT OF VARIOUS PROTEIN RATIONS ON THE SERUM PROTEIN CONCENTRATION OF THE RAT
Authors: Arthur L. Bloomfield
Journal: The Journal of Experimental Medicine (1935)

1. The effect of various percentages of protein (casein) in the diet on the serum protein concentration of the rat was studied. 2. With high protein rations (50 per cent or over) there is no drop at all of serum protein concentration, even though the diet is otherwise poorly balanced and inadequate as evidenced by weight loss. 3. With protein rations under 20 per cent the serum protein concentration falls promptly to a level of about 5.25–5.50 gm. per cent, where it is maintained regardless of whether the diet contains 1, 5, or 10 per cent of protein. Further depletion of the blood colloid concentration seems to meet with resistance on the part of the body.
Stimulation of fibroblast chemotaxis by human recombinant tumor necrosis factor alpha (TNF-alpha) and a synthetic TNF-alpha 31-68 peptide.
Authors: A E Postlethwaite, J M Seyer
Journal: The Journal of Experimental Medicine (1990)

Macrophages are a major source of fibrogenic factors that promote healing of injured tissue. The recruitment of fibroblasts to sites of tissue injury is a prerequisite for optimal repair of tissue damage. In the present study, human recombinant tumor necrosis factor alpha (hrTNF-alpha), a major macrophage-derived cytokine, was demonstrated to be a potent fibroblast chemoattractant, inducing migration at picomolar concentrations. Anti-hrTNF-alpha monoclonal antibody neutralized most of the fibroblast chemotactic activity generated during short-term culture of human peripheral blood monocytes stimulated with bacterial lipopolysaccharide, suggesting that TNF-alpha is a major monocyte-derived fibroblast chemoattractant. The portion of the human TNF-alpha molecule responsible for its chemotactic stimulation of fibroblasts appears to reside in residues 31-68. This region is highly conserved between TNF-alpha and lymphotoxin. This peptide is not only itself chemotactic but is also able to block the chemotactic response of fibroblasts to hrTNF-alpha and vice versa, suggesting that they each mediate fibroblast migration through similar mechanisms. These data further underscore the potential importance of TNF-alpha in modulating a variety of fibroblast functions, including chemotaxis and synthesis of collagen, glycosaminoglycans, interleukin 1 alpha (IL-1 alpha) and -beta, human histocompatibility leukocyte antigen A and B antigens, collagenase, prostaglandin E2, and IL-6.
Renal Production, Uptake, and Handling of Circulating αKlotho
Authors: Ming Chang Hu, Mingjun Shi, Jianning Zhang, Tayo Addo, Han Ju Cho, Sarah L. Barker, Priya Ravikumar, Nancy Gillings, Ao Bian, Sachdev S. Sidhu, Makoto Kuro-o, Orson W. Moe
Journal: Journal of the American Society of Nephrology (2015)

αKlotho is a multifunctional protein highly expressed in the kidney. Soluble αKlotho is released through cleavage of the extracellular domain from membrane αKlotho by secretases to function as an endocrine/paracrine substance. The role of the kidney in circulating αKlotho production and handling is incompletely understood, however. Here, we found higher αKlotho concentration in suprarenal compared with infrarenal inferior vena cava in both rats and humans. In rats, serum αKlotho concentration dropped precipitously after bilateral nephrectomy or upon treatment with inhibitors of αKlotho extracellular domain shedding. Furthermore, the serum half-life of exogenous αKlotho in anephric rats was four- to five-fold longer than that in normal rats, and exogenously injected labeled recombinant αKlotho was detected in the kidney and in urine of rats. Both in vivo (micropuncture) and in vitro (proximal tubule cell line) studies showed that αKlotho traffics from the basal to the apical side of the proximal tubule via transcytosis. Thus, we conclude that the kidney has dual roles in αKlotho homeostasis, producing and releasing αKlotho into the circulation and clearing αKlotho from the blood into the urinary lumen.
Development of mass spectrometry approaches to quantifying lipid mediators in airway disease
Authors: David Balgoma, Susanna L. Lundström, Anders Eklund, Johan Grunewald, Craig E. Wheelock
Journal: European Respiratory Journal (2011)

Background:  Lipid mediators (LMs, such as prostaglandins and leukotrienes) have been extensively studied for their role in both the onset and resolution of inflammation in airway diseases. We report here the development of a state-of-the-art quantitative lipidomics-based method for the analysis of LMs using Liquid Chromatography with Tandem Mass Spectrometry (LC-MS/MS).   Aims:  Develop a sensitive LC-MS/MS platform to quantify LMs from multiple biological matrices including urine, bronchoalveolar lavage fluid (BALF) and sputum. The method should encompass LMs from arachidonic (AA), linoleic (LA), dihomo-γ-linolenic (DGHLA), α-linolenic (α-LA), eicosapentaenoic (EPA) and docosahexaenoic (DHA) fatty acid pathways.   Methods:  Pooled BALF from patients with sarcoidosis (n=5) was extracted by Solid Phase Extraction and analytes were quantified by LC-MS/MS (Acquity-Xevo, Waters). The method assess 87 LMs in combination with 16 deuterated internal standards.   Results:  In BALF from sarcoidosis patients, 29 LMs from six fatty acid were detected; but only 8 LMs from each of the AA and LA pathways were quantifiable. The fatty acid origin and biosynthesis pathway of the 29 LMs is shown in Fig. 1.   Conclusions:  LC-MS/MS methods for LM quantification are applicable for exploring the etiology and pathology of respiratory diseases as exemplified with BALF from sarcoidosis patients. These methods will be useful in examining inflammatory processes.
Hypertrophic defect unmasked by calcineurin expression in asymptomatic tropomodulin overexpressing transgenic mice
Authors: M Sussman
Journal: Cardiovascular Research (2000)

Objective: Dilation and hypertrophy often occur concurrently in cardiomyopathy, yet the interaction between these two functionally distinct conditions remains unknown. Methods: Combinatorial effects of hypertrophy and dilation were investigated by cross-breeding of two cardiomyopathic transgenic mouse lines which develop either hypertrophy (calcineurin-mediated) or dilation (tropomodulin-mediated). Results: Altering the intensity of signals driving hypertrophy and dilation in cross-bred litters resulted in novel disease phenotypes different from either parental line. Augmenting the calcineurin-dependent hypertrophic stimulus in tropomodulin overexpressing transgenics elevated heart:body weight ratios, increased ventricular wall thickness, and significantly accelerated mortality. These effects were evident in calcineurin cross-breeding to tropomodulin backgrounds of transgene homozygosity (severe dilation) or heterozygosity (mild dilation to asymptomatic). Molecular analyses indicated that tropomodulin and calcineurin signaling events in the first week after birth were critical for determination of disease outcome, substantiated by demonstration that temporary neonatal inhibition of tropomodulin expression prevents dilation. Conclusions: This study shows that postnatal timing of altered signaling in cardiomyopathic transgenic mouse models is a pivotal part of determining outcome. In addition, intensifying hypertrophic stimulation exacerbates dilated cardiomyopathy, supporting the concept of shared molecular signaling between hypertrophy and dilation.
FGFR4 Blockade Exerts Distinct Antitumorigenic Effects in Human Embryonal versus Alveolar Rhabdomyosarcoma
Authors: Lisa E.S. Crose, Katherine T. Etheridge, Candy Chen, Brian Belyea, Lindsay J. Talbot, Rex C. Bentley, Corinne M. Linardic
Journal: Clinical Cancer Research (2012)

Abstract Purpose: Rhabdomyosarcoma (RMS) is a malignancy with features of skeletal muscle, and the most common soft tissue sarcoma of childhood. Survival for high-risk groups is approximately 30% at 5 years and there are no durable therapies tailored to its genetic aberrations. During genetic modeling of the common RMS variants, embryonal RMS (eRMS) and alveolar RMS (aRMS), we noted that the receptor tyrosine kinase (RTK) fibroblast growth factor receptor 4 (FGFR4) was upregulated as an early event in aRMS. Herein, we evaluated the expression of FGFR4 in eRMS compared with aRMS, and whether FGFR4 had similar or distinct roles in their tumorigenesis. Experimental Design: Human RMS cell lines and tumor tissue were analyzed for FGFR4 expression by immunoblot and immunohistochemistry. Genetic and pharmacologic loss-of-function of FGFR4 using virally transduced short hairpin RNA (shRNA) and the FGFR small-molecule inhibitor PD173074, respectively, were used to study the role of FGFR4 in RMS cell lines in vitro and xenografts in vivo. Expression of the antiapoptotic protein BCL2L1 was also examined. Results: FGFR4 is expressed in both RMS subtypes, but protein expression is higher in aRMS. The signature aRMS gene fusion product, PAX3-FOXO1, induced FGFR4 expression in primary human myoblasts. In eRMS, FGFR4 loss-of-function reduced cell proliferation in vitro and xenograft formation in vivo. In aRMS, it diminished cell survival in vitro. In myoblasts and aRMS, FGFR4 was necessary and sufficient for expression of BCL2L1 whereas in eRMS, this induction was not observed, suggesting differential FGFR4 signaling. Conclusion: These studies define dichotomous roles for FGFR4 in RMS subtypes, and support further study of FGFR4 as a therapeutic target. Clin Cancer Res; 18(14); 3780–90. ©2012 AACR.
Sex Chromosomes Evolved from Independent Ancestral Linkage Groups in Winged Insects
Authors: James B. Pease, Matthew W. Hahn
Journal: Molecular Biology and Evolution (2012)

The evolution of a pair of chromosomes that differ in appearance between males and females (heteromorphic sex chromosomes) has occurred repeatedly across plants and animals. Recent work has shown that the male heterogametic (XY) and female heterogametic (ZW) sex chromosomes evolved independently from different pairs of homomorphic autosomes in the common ancestor of birds and mammals but also that X and Z chromosomes share many convergent molecular features. However, little is known about how often heteromorphic sex chromosomes have either evolved convergently from different autosomes or in parallel from the same pair of autosomes and how universal patterns of molecular evolution on sex chromosomes really are. Among winged insects with sequenced genomes, there are male heterogametic species in both the Diptera (e.g., Drosophila melanogaster) and the Coleoptera (Tribolium castaneum), female heterogametic species in the Lepidoptera (Bombyx mori), and haplodiploid species in the Hymenoptera (e.g., Nasonia vitripennis). By determining orthologous relationships among genes on the X and Z chromosomes of insects with sequenced genomes, we are able to show that these chromosomes are not homologous to one another but are homologous to autosomes in each of the other species. These results strongly imply that heteromorphic sex chromosomes have evolved independently from different pairs of ancestral chromosomes in each of the insect orders studied. We also find that the convergently evolved X chromosomes of Diptera and Coleoptera share genomic features with each other and with vertebrate X chromosomes, including excess gene movement from the X to the autosomes. However, other patterns of molecular evolution—such as increased codon bias, decreased gene density, and the paucity of male-biased genes on the X—differ among the insect X and Z chromosomes. Our results provide evidence for both differences and nearly universal similarities in patterns of evolution among independently derived sex chromosomes.
Short consensus repeat-3 domain of recombinant decay-accelerating factor is recognized by Escherichia coli recombinant Dr adhesin in a model of a cell-cell interaction.
Authors: B Nowicki, A Hart, K E Coyne, D M Lublin, S Nowicki
Journal: The Journal of Experimental Medicine (1993)

A bacterial pathogen that is important in both urinary tract and intestinal infections is Escherichia coli which expresses Dr or related adhesins. In this report, we present a model for testing cell-cell interaction, using both molecularly characterized laboratory cells that express recombinant molecules of human decay-accelerating factor (DAF), and recombinant bacterial Dr colonization factors. Dr adhesin ligand was identified as DAF (CD55), a membrane protein that protects autologous tissues from damage due to the complement system. Structure-function studies mapped the adhesin-binding site on the DAF molecule. A single-point substitution in the third short consensus repeat domain, Ser165 to Leu, corresponding to the Dra to Drb allelic polymorphism, caused complete abolition of adhesin binding to DAF.