tbuckley/cabot-search huggingface dataset:
Proxy-reported questionnaires for young children with asthma: a structured review
Authors: Amy Barrett, Marci Clark, Carla DeMuro, Dirk Esser
Journal: European Respiratory Journal (2012)

Which proxy-reported outcome measures have been developed for use with children aged 6 years and younger to assess asthma symptoms, asthma control, and asthma-specific health-related quality of life, and do these questionnaires' measurement properties support their use as end-points in clinical trials? A two-phase literature search was conducted: 1) studies describing relevant questionnaires were identified, and the questionnaires were assessed against predefined criteria; 2) studies providing information on the measurement properties of questionnaires meeting the predefined inclusion criteria were identified. Literature sources included PubMed and EMBASE databases, scientific conference proceedings, a clinical trial registry, and a quality of life instrument database. The initial search of literature databases and conference abstracts identified 631 records. 20 paediatric asthma proxy-reported outcome instruments were identified; seven met the inclusion criteria: Childhood Asthma Control Test, Control de Asma en Niños Questionnaire, Pediatric Asthma Caregiver Diary, Pediatric Asthma Control Tool, PedsQL 3.0 Short-Form 22 Asthma Module, PedsQL Asthma Symptoms Scale, and Test for Respiratory and Asthma Control in Kids. Three proxy-reported outcome instruments were considered suitable for use as end-points in paediatric asthma clinical trials; the Pediatric Asthma Caregiver Diary possesses the strongest measurement properties of the three.
Fes-Cre Targets Phosphatidylinositol Glycan Class a (Piga) Inactivation to Hematopoietic Stem Cells in the Bone Marrow
Authors: Peter Keller, Jennifer L. Payne, Gabi Tremml, Peter A. Greer, Mirella Gaboli, Pier P. Pandolfi, Monica Bessler
Journal: The Journal of Experimental Medicine (2001)

A somatic mutation in the X-linked phosphatidylinositol glycan class A (PIGA) gene causes the loss of glycosyl phosphatidylinositol (GPI)-linked proteins on blood cells from patients with paroxysmal nocturnal hemoglobinuria. Because all blood cell lineages may be affected it is thought that the mutation occurs in a hematopoietic stem cell. In transgenic mice, germline transmission of an inactive Piga gene is embryonic lethal. To inactivate the murine Piga gene in early hematopoiesis we therefore chose conditional gene inactivation using the Cre/loxP system. We expressed Cre recombinase under the transcription regulatory sequences of the human c-fes gene. FES-Cre inactivated PIGA in hematopoietic cells of mice carrying a floxed Piga allele (LF mice). PIGA− cells were found in all hematopoietic lineages of definitive but not primitive hematopoiesis. Their proportions were low in newborn mice but subsequently increased continuously to produce for the first time mice that have almost exclusively PIGA− blood cells. The loss of GPI-linked proteins occurred mainly in c-kit+CD34+Lin− progenitor cells before the CFU-GEMM stage. Using bone marrow reconstitution experiments with purified PIGA− cells we demonstrate that LF mice have long-term bone marrow repopulating cells that lack GPI-linked proteins, indicating that recombination of the floxed Piga allele occurs in the hematopoietic stem cell.
Saline or Albumin for Fluid Resuscitation in Patients with Traumatic Brain Injury
Authors: John Myburgh, D. James Cooper, Rinaldo Bellomo, Robyn Norton, Nicole Bish
Journal: New England Journal of Medicine (2007)

The Saline versus Albumin Fluid Evaluation study suggested that patients with traumatic brain injury resuscitated with albumin had a higher mortality rate than those resuscitated with saline. We conducted a post hoc follow-up study of patients with traumatic brain injury who were enrolled in the study.
Does Yohimbine Hydrochloride Facilitate Fear Extinction in Virtual Reality Treatment of Fear of Flying? A Randomized Placebo-Controlled Trial
Authors: Katharina Meyerbroeker, Mark B. Powers, Anda van Stegeren, Paul M.G. Emmelkamp
Journal: Psychotherapy and Psychosomatics (2011)

&lt;i&gt;Background:&lt;/i&gt; Research suggests that yohimbine hydrochloride (YOH), a noradrenaline agonist, can facilitate fear extinction. It is thought that the mechanism of enhanced emotional memory is stimulated through elevated noradrenaline levels. This randomized placebo-controlled trial examined the potential exposure-enhancing effects of YOH in a clinical sample of participants meeting DSM-IV criteria for a specific phobia (fear of flying). &lt;i&gt;Methods:&lt;/i&gt; Sixty-seven participants with fear of flying were randomized to 4 sessions of virtual reality exposure therapy (VRET) combined with YOH (10 mg), or 4 sessions of VRET combined with a placebo. Treatment consisted of 4 weekly 1-hour exposure sessions consisting of two 25-minute virtual flights. At pre- and post- treatment, fear of flying was assessed. The YOH or placebo capsules were administered 1 h prior to exposures. The manipulation of the noradrenaline activity was confirmed by salivary α-amylase (sAA) samples taken pre-, during and post-exposure. &lt;i&gt;Results:&lt;/i&gt; Forty-eight participants completed treatment. Manipulation of noradrenaline levels with YOH was successful, with significantly higher levels of sAA in the YOH group when entering exposure. Results showed that both groups improved significantly from pre- to post-treatment with respect to anxiety reduction. However, although the manipulation of noradrenaline activity was successful, there was no evidence that YOH enhanced outcome. &lt;i&gt;Conclusions:&lt;/i&gt; Participants improved significantly on anxiety measures independently of drug condition, after 4 sessions of VRET. These data do not support the initial findings of exposure-enhancing effects of YOH in this dosage in clinical populations.
Chlamydia trachomatis and Risk of Prevalent and Incident Cervical Premalignancy in a Population-Based Cohort
Authors: Mahboobeh Safaeian, Koen Quint, Mark Schiffman, Ana Cecilia Rodriguez, Sholom Wacholder, Rolando Herrero, Allan Hildesheim, Raphael P. Viscidi, Wim Quint, Robert D. Burk
Journal: JNCI Journal of the National Cancer Institute (2010)

Cofactors might affect the risk of the rare progression from infection with carcinogenic human papillomavirus (HPV) to cervical premalignancy to invasive cancer. Some studies have observed that Chlamydia trachomatis infection is associated with increased risk for cervical cancer. In a large prospective cohort, we assessed the role of C trachomatis in cervical premalignancy and addressed confounding by HPV. We identified 182 women with prevalent and 132 women with incident histological cervical intraepithelial neoplasia grade 2 (CIN2), grade 3 (CIN3), or cervical cancer (CIN2+) in the Costa Rica HPV Natural History Study. Control subjects were 995 (approximately 10% of the 10 049) subjects who were randomly selected from the same study. Cervical HPV status at enrollment was determined by MY09/MY11 polymerase chain reaction amplification and dot-blot hybridization. The presence of C trachomatis DNA in cervical exfoliated cells at enrollment was determined by a novel serovar-specific polymerase chain reaction–based C trachomatis detection and genotyping assay. Plasma drawn at enrollment from each subject was used to determine C trachomatis immunoglobulin G (IgG) status. Logistic regression was used to examine the association between C trachomatis and CIN2+, taking into account possible confounding by HPV. C trachomatis positivity at enrollment was associated with CIN2+ and concurrent and subsequent carcinogenic HPV infection. To account for confounding by HPV status, we restricted the analysis to women positive for carcinogenic HPV DNA at enrollment and found no association between C trachomatis status (as assessed by DNA or IgG) at enrollment and combined prevalent and/or incident CIN2+ (for C trachomatis DNA positivity, odds ratio = 0.77, 95% confidence interval = 0.42 to 1.41; for C trachomatis seropositivity, odds ratio = 1.09, 95% confidence interval = 0.85 to 1.41). We found no association between C trachomatis status, as assessed by DNA or IgG, and risk of cervical premalignancy, after controlling for carcinogenic HPV-positive status. Previous positive associations between C trachomatis and cervical premalignancy could have been caused, in part, by an increased susceptibility to HPV infection.
The “Milk Factor” in Carcinoma of the Human Breast
Authors: Herbert W. Horne
Journal: New England Journal of Medicine (1950)

THE purpose of this study was to explore the possibility of the vertical transfer through breast feeding of an agent that might be a factor in the development of human mammary cancer. Complete bibliographic material on the subject is presented by Berner elsewhere in this issue of the Journal.The difficulties of this type of study, in which the memory of the mother for an event that took place often forty or fifty years before serves as the major criterion, are fully realized. At the start of the investigation, it appeared necessary to have a control group. The possibility . . .
Signal Transducer and Activator of Transcription 1 Is Required for Optimal Foam Cell Formation and Atherosclerotic Lesion Development
Authors: Sudesh Agrawal, Maria Febbraio, Eugene Podrez, Martha K. Cathcart, George R. Stark, Guy M. Chisolm
Journal: Circulation (2007)

Background— Signal transducer and activator of transcription 1 (Stat1) potently regulates gene expression after stimulation by certain cytokines involved in tumorigenesis and host defenses. The present study investigated a novel role for Stat1 in foam cell formation and atherosclerosis. Methods and Results— Inhibition of Stat1 activity by a Stat1-specific DNA “decoy” oligomer transfected into differentiated human THP-1 cells, and deficiency of stat1 in mouse macrophages significantly inhibited foam cell formation assessed by lipid staining and cholesteryl ester accumulation compared with control cells. The mechanism of Stat1 regulation of foam cell formation was uniquely dependent on the scavenger receptor CD36. Blunted Stat1 activity and stat1 deficiency significantly decreased expression of CD36 but not of scavenger receptor-A compared with controls, as assessed by immunoblotting and flow cytometry. Deficiency of CD36 but not scavenger receptor-A in mouse macrophages removed any dependency of foam cell formation on Stat1. In an intraperitoneal model of foam cell formation in which foam cells form in vivo independently of the model ligands used in vitro, stat1 deficiency significantly inhibited foam cell formation and CD36 expression. Transplantation of bone marrow from apolipoprotein e − / − × stat1 − / − mice into lethally irradiated, atherosclerosis-susceptible apolipoprotein e −/− recipients significantly reduced both en face aortic lesion coverage and aortic root lesions compared with recipients of bone marrow from genetically matched apolipoprotein e −/− mice. Conclusions— Stat1 regulates CD36 expression and foam cell formation in macrophages in vitro; the Stat1 regulation of foam cell formation requires CD36. The regulation of CD36 expression by Stat1 may be important in other pathophysiological CD36-dependent events. Stat1 deficiency reduces atherosclerosis in an apolipoprotein e −/− atherosclerosis-susceptible bone marrow transplantation model.
Risk Factors for Accelerated Decline Among Patients with Chronic Obstructive Pulmonary Disease
Authors: Huib A. M. Kerstjens, Paul L. P. Brand, Dirkje S. Postma
Journal: American Journal of Respiratory and Critical Care Medicine (1996)

"Risk Factors for Accelerated Decline Among Patients with Chronic Obstructive Pulmonary Disease." American Journal of Respiratory and Critical Care Medicine, 154(6_pt_2), pp. S266–S272
Proinflammatory Modulation of the Surface and Cytokine Phenotype of Monocytes in Patients With Acute Charcot Foot
Authors: Luigi Uccioli, Anna Sinistro, Cristiana Almerighi, Chiara Ciaprini, Antonella Cavazza, Laura Giurato, Valeria Ruotolo, Francesca Spasaro, Erika Vainieri, Giovanni Rocchi, Alberto Bergamini
Journal: Diabetes Care (2009)

Despite increased information on the importance of an inappropriate inflammatory response in the acute Charcot process, there has been no previous attempt to define the specific pathways that mediate its pathogenesis. Here, the role played by monocytes was analyzed.The immune phenotype of peripheral monocytes was studied by fluorescence-activated cell sorter analysis comparing patients with acute Charcot (n = 10) in both the active and recovered phase, diabetic patients with neuropathy (with or without osteomyelitis), and normal control subjects.When compared with diabetic control subjects and healthy subjects, monocytes from acute Charcot patients showed a proinflammatory immune phenotype characterized by increased production of proinflammatory cytokines, reduced secretion of anti-inflammatory cytokines, increased expression of surface costimulatory molecules, and increased resistance to serum withdrawal-induced apoptosis. In addition, the pattern of circulating cytokines confirmed activation of proinflammatory cytokines. No modulation of the monocyte phenotype was documented in diabetic control subjects and healthy subjects, thus indicating that the proinflammatory alterations of monocytes are specific and causative of acute Charcot.Together, these data provide evidence for the role of proinflammatory changes in the immune phenotype of monocytes in the pathogenesis of acute Charcot. These alterations may explain the abnormally intense and prolonged inflammatory response that characterizes this disorder and may represent a potential therapeutic target for specific pharmacological interventions.
Cardiovascular <i>Ecto</i> -5′-Nucleotidase
Authors: Ray A. Olsson
Journal: Circulation Research (2004)

lsewhere in this issue, Koszalka et al 1 add another chapter to the long-running saga of the significance of ecto-5Ј-nucleotidase (CD-73) in cardiovascular function, showing that this enzyme catalyzes the formation of adenosine in amounts sufficient to have important physiological effects.A brief sketch of the tortuous path to our present understanding of the role of this enzyme puts this work in perspective.It also illustrates how science evolves stepwise, testing hypotheses based on available evidence and modifying them to fit the new evidence.In the early 1960s, Berne 2 and, independently, Gerlach et al 3 showed that hypoxia stimulated adenosine production in the heart.Within a few years, histochemists showed phosphatase activity able to hydrolyze AMP on the surface of cardiac and skeletal muscle myocytes.At first this seemed to provide an explanation for the adenosine released from hypoxic heart muscle, but there was a serious problem.The enzyme was outside the cell, but its substrate, AMP, was in the cytoplasm, separated by a sarcolemma thought at the time to be impermeable to nucleotides.Theories advanced to resolve this dilemma included the idea that the ectoenzyme also had transport capacity, but this faltered for lack of direct evidence.There was little further progress for approximately a decade, in part because the discovery of nitric oxide-mediated vasodilation 4 dispelled the notion that adenosine was "the" regulator of coronary vascular resistance.Then, Japanese and American workers isolated cytosolic nucleotidases, and Andrew Newby clinched the importance of the cytosolic enzyme by showing that leukocytes poisoned with 2-deoxyglucose still produced adenosine despite inactivation of the ectoenzyme by antibodies directed against it. 5Cloning the genes for the cytosolic enzyme in the late 1990s seemed the final step in establishing the cytosol as the site of adenosine production.By then, thinking about the function of CD73 had largely shifted to its role as a B lymphocyte adhesion molecule. 6owever, there were still inconsistencies in the evidence supporting a solely cytosolic origin of cardiac adenosine.Inhibitors of the equilibrative nucleoside transporter, which
Clinicopathological Characteristics and Outcomes of Breast Cancer Patients with Collagen Disorders
Authors: A. Osaki, H. Shimada, I. Sugitani, M. Sugiyama, E. Hirokawa, H. Sano, N. Nakamiya, S. Ueda, T. Shigekawa, H. Takeuchi, T. Takahashi, T. Saeki
Journal: Annals of Oncology (2014)
Modeling Boundary Conditions for Balanced Proliferation in Metastatic Latency
Authors: Donald P. Taylor, Jakob Z. Wells, Andrej Savol, Chakra Chennubhotla, Alan Wells
Journal: Clinical Cancer Research (2013)

Nearly half of cancer metastases become clinically evident five or more years after primary tumor treatment; thus, metastatic cells survived without emerging for extended periods. This dormancy has been explained by at least two countervailing scenarios: cellular quiescence and balanced proliferation; these entail dichotomous mechanistic etiologies. To examine the boundary parameters for balanced proliferation, we conducted in silico modeling.To illuminate the balanced proliferation hypothesis, we explored the specific boundary probabilities under which proliferating micrometastases would remain dormant. A two-state Markov chain Monte Carlo model simulated micrometastatic proliferation and death according to stochastic survival probabilities. We varied these probabilities across 100 simulated patients each with 1,000 metastatic deposits and documented whether the micrometastases exceeded one million cells, died out, or remained dormant (survived 1,218 generations).The simulations revealed a narrow survival probability window (49.7-50.8%) that allowed for dormancy across a range of starting cell numbers, and even then for only a small fraction of micrometastases. The majority of micrometastases died out quickly even at survival probabilities that led to rapid emergence of a subset of micrometastases. Within dormant metastases, cell populations depended sensitively on small survival probability increments.Metastatic dormancy as explained solely by balanced proliferation is bounded by very tight survival probabilities. Considering the far larger survival variability thought to attend fluxing microenvironments, it is more probable that these micrometastatic nodules undergo at least periods of quiescence rather than exclusively being controlled by balanced proliferation.
Should patients with sleep apnoea/hypopnoea syndrome be diagnosed and managed on the basis of home sleep studies?
Authors: O Parra, N Garcia-Esclasans, JM Montserrat, L Garcia Eroles, J Ruiz, JA Lopez, JM Guerra, JJ Sopena
Journal: European Respiratory Journal (1997)

The purpose of this study was to analyse the validity and the economic efficiency of a portable monitor of respiratory parameters (PMRP), used in a home setting for the diagnosis of sleep apnoea/hypopnoea syndrome (SAHS). Eighty nine patients with suspected SAHS were studied in two settings: in the sleep laboratory using full-polysomnography (full-PSG); and at the patient's home using a PMRP. In the home setting, 50 patients were assisted by a technician and 39 set up the equipment themselves. SAHS (apnoea/hypopnoea index (AHI) &gt;10 events x h(-1) by means of full-PSG) was diagnosed in 75 of the 89 patients. An acceptable agreement was obtained between the AHI measured by full-PSG and PMRP, according to the Bland and Altman method of concordance (mean bias 2.56; 95% confidence interval 3.25). Sensitivity and specificity of PMRP were adequate for diagnostic purposes; however, their values rely on the prior PMRP-AHI cut-off point selected with reference to full-PSG-AHI &gt;10. The clinical therapeutic decision taken after PMRP agreed with that taken with full-PSG in 79 patients (89%). Although 10% of the studies with an individual set-up needed repetition, both of the domiciliary modalities (with and without a technician's intervention) were, economically, about three times more efficient than full-PSG. In conclusion, we believe that patients with a suspected sleep apnoea/hypopnoea syndrome should initially be studied in a home setting with a portable monitor of respiratory parameters, since it is a reliable method with an acceptable cost-effective profile.
Short, Full-Dose Adjuvant Chemotherapy in High-Risk Adult Soft Tissue Sarcomas: A Randomized Clinical Trial From the Italian Sarcoma Group and the Spanish Sarcoma Group
Authors: Alessandro Gronchi, Sergio Frustaci, Mario Mercuri, Javier Martin, Antonio Lopez-Pousa, Paolo Verderio, Lidia Mariani, Pinuccia Valagussa, Rosalba Miceli, Silvia Stacchiotti, Angelo Paolo Dei Tos, Antonino De Paoli, Alessandra Longhi, Andres Poveda, Vittorio Quagliuolo, Alessandro Comandone, Paolo Giovanni Casali, Piero Picci
Journal: Journal of Clinical Oncology (2012)

Purpose A previous randomized clinical trial by the Italian Sarcoma Group (ISG) had shown a survival benefit of adjuvant chemotherapy (CT) in high-risk extremity soft tissue sarcoma (STS). However, the dose-intensity of the last two cycles was suboptimal. We then undertook a multicentric international phase III study to compare three and five cycles of the same CT. Patients and Methods Patients were randomly assigned either to receive three cycles of preoperative CT with epirubicin 120 mg/m 2 and ifosfamide 9 g/m 2 and granulocyte colony-stimulating factor (arm A) or to receive the same three cycles of preoperative CT followed by two further cycles of postoperative CT (arm B). Noninferiority of the primary end point, overall survival (OS), was assessed by the CI of the hazard ratio (HR; arm A/arm B) obtained from the Cox model. Results Between January 2002 and April 2007, 328 patients were recruited (164 patients in each arm). At a median follow-up of 63 months (interquartile range, 49 to 77 months), 100 deaths were recorded, 49 in arm A and 51 in arm B. Five-year OS probability was 0.70 for the entire group of patients (0.68 in arm A and 0.71 in arm B). The HR of arm A versus arm B was 1.00 (90% CI, 0.72 to 1.39). Conclusion In this population of patients with high-risk localized STS, three cycles of full-dose preoperative CT were not inferior to five cycles. The outcome compares favorably with the expected survival of patients with high-risk STS and was superimposable on the CT arm of the previous ISG trial.
Acute vertebral osteomyelitis complicating Streptococcus sanguis endocarditis.
Authors: C Demers, M Tremblay, Y Lacourciere
Journal: Annals of the Rheumatic Diseases (1988)

The first well documented case of acute pyogenic vertebral osteomyelitis presenting as the initial manifestation of Streptococcus sanguis endocarditis is reported. The importance of suspecting vertebral osteomyelitis in the presence of disc infection and the diagnostic value of imaging procedures are underlined.