tbuckley/cabot-search huggingface dataset:
Concussion management by paediatricians: a national survey of Canadian paediatricians
Authors: Kevin Gordon, Minh T Do, Wendy Thompson, Steven McFaull
Journal: British Journal of Sports Medicine (2013)

Objective To determine: (a) concussion/mTBI guideline use, (b) criteria used in initiating return to play (RTP), and (c) the management of RTP by Canadian paediatricians. Design Cross-sectional survey. Subjects Sample of 2599 Canadian paediatric specialists and subspecialists. Methods The Canadian Paediatric Surveillance Program provided the sampling frame and survey management. Potential participants were sent a seven-item survey inquiring whether they managed children with concussion, and if so, which guidelines they used, and their initiating RTP criteria and duration. Results 809 paediatricians responded (31%), with 503 eligible for the study by indicating that they managed children/youth with newly diagnosed with concussion/mTBI. They reported collectively managing approximately 6700 children/youth within the last 12 months (2010–2011). They reported using many concussion/mTBI guidelines: Canadian Paediatric Society (n=244), American Academy of Paediatrics (n=101), Concussion in Sport Group (n=68), Canadian Academy of Sport and Exercise Medicine (n=58), and the American Academy of Neurology (n=25). Similarly, different criteria were used to determine asymptomatic status. Most common were: free from all concussion symptoms, by patient report (n=323), by proxy report (parent/other) (n=269), and free from continuous daily (unremitting) headache (n=162). Of those reporting, most (∼85%) indicated that they did not initiate RTP immediately after their patients became asymptomatic. The median recommend time before initiating RTP was 7 days. Conclusions Concussions/mTBI are frequently encountered by Canadian paediatricians. There is heterogeneity in the guidelines used and the criteria used to determine when patients become asymptomatic with most recommending asymptomatic time before starting RTP. Competing interests None.
Evolution of a Genome-Encoded Bias in Amino Acid Biosynthetic Pathways Is a Potential Indicator of Amino Acid Dynamics in the Environment
Authors: Rick A. Fasani, Michael A. Savageau
Journal: Molecular Biology and Evolution (2014)

Overcoming the stress of starvation is one of an organism’s most challenging phenotypic responses. Those organisms that frequently survive the challenge, by virtue of their fitness, will have evolved genomes that are shaped by their specific environments. Understanding this genotype–environment–phenotype relationship at a deep level will require quantitative predictive models of the complex molecular systems that link these aspects of an organism’s existence. Here, we treat one of the most fundamental molecular systems, protein synthesis, and the amino acid biosynthetic pathways involved in the stringent response to starvation. These systems face an inherent logical dilemma: Building an amino acid biosynthetic pathway to synthesize its product—the cognate amino acid of the pathway—may require that very amino acid when it is no longer available. To study this potential “catch-22,” we have created a generic model of amino acid biosynthesis in response to sudden starvation. Our mathematical analysis and computational results indicate that there are two distinctly different outcomes: Partial recovery to a new steady state, or full system failure. Moreover, the cell’s fate is dictated by the cognate bias, the number of cognate amino acids in the corresponding biosynthetic pathway relative to the average number of that amino acid in the proteome. We test these implications by analyzing the proteomes of over 1,800 sequenced microbes, which reveals statistically significant evidence of low cognate bias, a genetic trait that would avoid the biosynthetic quandary. Furthermore, these results suggest that the pattern of cognate bias, which is readily derived by genome sequencing, may provide evolutionary clues to an organism’s natural environment.
Prediction of Specific Airway Responsiveness from Skin Sensitivity to Allergen and Airway Hyperresponsiveness to Methacholine in Baker's Asthma
Authors: S. Quirce, M. Fernández-Nieto, C. Escudero, J. Cuesta, M. de las Heras, J. Sastre
Journal: Journal of Allergy and Clinical Immunology (2006)
A Clinico-microbiological Study of Diabetic Foot Ulcers in an Indian Tertiary Care Hospital
Authors: Ravisekhar Gadepalli, Benu Dhawan, Vishnubhatla Sreenivas, Arti Kapil, A.C. Ammini, Rama Chaudhry
Journal: Diabetes Care (2006)

To determine the microbiological profile and antibiotic susceptibility patterns of organisms isolated from diabetic foot ulcers. Also, to assess potential risk factors for infection of ulcers with multidrug-resistant organisms (MDROs) and the outcome of these infections.Pus samples for bacterial culture were collected from 80 patients admitted with diabetic foot infections. All patients had ulcers with Wagner's grade 3-5. Fifty patients (62.5%) had coexisting osteomyelitis. Gram-negative bacilli were tested for extended spectrum beta-lactamase (ESBL) production by double disc diffusion method. Staphylococcal isolates were tested for susceptibility to oxacillin by screen agar method, disc diffusion, and mec A-based PCR. Potential risk factors for MDRO-positive samples were explored.Gram-negative aerobes were most frequently isolated (51.4%), followed by gram-positive aerobes and anaerobes (33.3 and 15.3%, respectively). Seventy-two percent of patients were positive for MDROs. ESBL production and methicillin resistance was noted in 44.7 and 56.0% of bacterial isolates, respectively. MDRO-positive status was associated with presence of neuropathy (P = 0.03), osteomyelitis (P = 0.01), and ulcer size >4 cm(2) (P < 0.001) but not with patient characteristics, ulcer type and duration, or duration of hospital stay. MDRO-infected patients had poor glycemic control (P = 0.01) and had to be surgically treated more often (P < 0.01).Infection with MDROs is common in diabetic foot ulcers and is associated with inadequate glycemic control and increased requirement for surgical treatment. There is a need for continuous surveillance of resistant bacteria to provide the basis for empirical therapy and reduce the risk of complications.
Chemopreventative Potential of the Cruciferous Vegetable Constituent Phenethyl Isothiocyanate in a Mouse Model of Prostate Cancer
Authors: Anna A. Powolny, Ajay Bommareddy, Eun-Ryeong Hahm, Daniel P. Normolle, Jan H. Beumer, Joel B. Nelson, Shivendra V. Singh
Journal: JNCI Journal of the National Cancer Institute (2011)

BackgroundThis study was undertaken to determine the chemopreventative efficacy of phenethyl isothiocyanate (PEITC), a bioactive constituent of many edible cruciferous vegetables, in a mouse model of prostate cancer, and to identify potential biomarker(s) associated with PEITC response.
No Significant Correlation Exists Between Core Promoter Mutations, Viral Replication, and Liver Damage in Chronic Hepatitis B Infection
Authors: Yoon Keun Chun, Jee Youn Kim, Hong Jung Woo, Soo Myung Oh, Insug Kang, Joohun Ha, Sung Soo Kim
Journal: Hepatology (2000)

Hepatitis B virus (HBV) core promoter mutants have been proposed to contribute to severe liver damage by increasing viral loads, but this has not yet been clearly shown. To examine the effects of core promoter mutants on viral load and liver damage, we first developed a polymerase chain reaction (PCR)-based semiquantitative HBV DNA detection method with a high sensitivity (able to detect as low as 10(3) molecules/mL). Then we cloned 12 predominant core promoter mutants from 41 chronic hepatitis B patients. The in vitro promoter and replication activities of these mutants were similar to those of wild-type virus. However, viral load was highly variable, and this was dependent on individual patients rather than mutant type. In addition, there was no mutant type that showed any unique correlation with alanine transaminase (ALT) levels. Viral load was not significantly correlated with ALT level in both cross-sectional and longitudinal studies. Quantitation of HBV levels also revealed no clear correlation between hepatitis B e antigen (HBeAg) status and viral load. Taken together, these results indicated that the replication activity of core promoter mutants has little effect on viral load, and that viral load does not correlate with the severity of liver damage or with HBeAg status.
Molecular cloning and characterization of the constitutive bovine aortic endothelial cell nitric oxide synthase.
Authors: K Nishida, D G Harrison, J P Navas, A A Fisher, S P Dockery, M Uematsu, R M Nerem, R W Alexander, T J Murphy
Journal: Journal of Clinical Investigation (1992)

The constitutive endothelial cell nitric oxide synthase (NOS) importantly regulates vascular homeostasis. To gain understanding of this enzyme, a pEF BOS cDNA library of 5 x 10(5) clones was prepared from bovine aortic endothelial cells (BAEC) and screened with a 2.8-kb cDNA BamHI fragment of rat brain NOS. Clone pBOS13 was found to express NO synthase activity when transfected into COS-7 cells. Sequence analysis revealed sequences compatible with binding domains for calcium/calmodulin, flavin mononucleotide, flavin adenine nucleotide and NADPH. The deduced amino acid sequence revealed a protein with a relative mol mass of 133,286, which is 58% homologous to the rat cerebellar NOS and 51% homologous to the mouse macrophage NOS. The amino-terminal portion of the protein exhibits several characteristics peculiar to the endothelial cell NOS. These include a proline-rich region and several potential sites for proline-directed phosphorylation as well as a potential substrate site for acyl transferase. Northern hybridization to mRNA from cultured BAEC revealed an abundant 4.8-kb message, which was not increased by coincubation with tumor necrosis factor alpha, but was markedly increased by exposure to shear stress for 24 h. The unique features of the endothelial cell NO synthase, particularly in the amino terminal portion of the molecule, may provide for novel regulatory influences of enzyme activity and localization.
Urokinase Receptor Deficiency Accelerates Renal Fibrosis in Obstructive Nephropathy
Authors: Guoqiang Zhang, Heungsoo Kim, Xiaohe Cai, Jesús M. López-Guisa, Charles E. Alpers, Youhua Liu, Peter Carmeliet, Allison A. Eddy
Journal: Journal of the American Society of Nephrology (2003)

ABSTRACT. The urokinase cellular receptor (uPAR) recognizes the N-terminal growth factor domain of urokinase-type plasminogen activator (uPA) and is expressed by several cell types. The present study was designed to test the hypothesis that uPAR regulates the renal fibrogenic response to chronic injury. Groups of uPAR wild-type (+/+) and deficient (−/−) mice were investigated between 3 and 14 d after unilateral ureteral obstruction (UUO) or sham surgery. Not detected in normal kidneys, uPAR mRNA was expressed in response to UUO in the +/+ mice. By <i>in situ</i> hybridization, uPAR mRNA transcripts were detected in renal tubules and interstitial cells of the obstructed uPAR+/+ kidneys. The severity of renal fibrosis, based on the measurement of total collagen (13.5 ± 1.5 <i>versus</i> 9.8 ± 1.0 μg/mg kidney on day 14; −/− <i>versus</i> +/+) and interstitial area stained by Masson trichrome (22 ± 4% <i>versus</i> 14 ± 3% on day 14; −/− <i>versus</i> +/+) was significantly greater in the uPAR−/− mice. In the absence of uPAR, renal uPA activity was significantly decreased compared with the wild-type animals after UUO (62 ± 20 <i>versus</i> 135 ± 13 units at day 3 UUO; 74 ± 17 <i>versus</i> 141 ± 16 at day 7 UUO; 98 ± 20 <i>versus</i> 165 ± 10 at day 14 UUO; −/− <i>versus</i> +/+). In contrast, renal expression of several genes that regulate plasmin activity were similar in both genotypes, including uPA, tPA, PAI-1, protease nexin-1, and α2-antiplasmin. Worse renal fibrosis in the uPAR−/− mice appears to be TGF-β-independent, as TGF-β activity was actually reduced by 65% in the −/− mice despite similar renal TGF-β1 mRNA levels. Significantly lower levels of the major 2.3-kb transcript and the 69-kd active protein of hepatocyte growth factor (HGF), a known anti-fibrotic growth factor, in the uPAR−/− mice suggests a potential link between HGF and the renoprotective effects of uPAR. These data suggest that renal uPAR attenuates the fibrogenic response to renal injury, an outcome that is mediated in part by urokinase-dependent but plasminogen-independent functions. E-mail: allison.eddy@seattlechildrens.org
A DNA Repair Pathway–Focused Score for Prediction of Outcomes in Ovarian Cancer Treated With Platinum-Based Chemotherapy
Authors: Josephine Kang, Alan D. D’Andrea, David Kozono
Journal: JNCI Journal of the National Cancer Institute (2012)

BackgroundNew tools are needed to predict outcomes of ovarian cancer patients treated with platinum-based chemotherapy. We hypothesized that a molecular score based on expression of genes that are involved in platinum-induced DNA damage repair could provide such prognostic information.
Fluid Mechanics of Vascular Systems, Diseases, and Thrombosis
Authors: David M. Wootton, David N. Ku
Journal: Annual Review of Biomedical Engineering (1999)

▪ Abstract The cardiovascular system is an internal flow loop with multiple branches circulating a complex liquid. The hallmarks of blood flow in arteries are pulsatility and branches, which cause wall stresses to be cyclical and nonuniform. Normal arterial flow is laminar, with secondary flows generated at curves and branches. Arteries can adapt to and modify hemodynamic conditions, and unusual hemodynamic conditions may cause an abnormal biological response. Velocity profile skewing can create pockets in which the wall shear stress is low and oscillates in direction. Atherosclerosis tends to localize to these sites and creates a narrowing of the artery lumen—a stenosis. Plaque rupture or endothelial injury can stimulate thrombosis, which can block blood flow to heart or brain tissues, causing a heart attack or stroke. The small lumen and elevated shear rate in a stenosis create conditions that accelerate platelet accumulation and occlusion. The relationship between thrombosis and fluid mechanics is complex, especially in the post-stenotic flow field. New convection models have been developed to predict clinical occlusion from platelet thrombosis in diseased arteries. Future hemodynamic studies should address the complex mechanics of flow-induced, large-scale wall motion and convection of semisolid particles and cells in flowing blood.
Leapfrogging Data
Authors: Marc A. Pfeffer, Frank M. Sacks
Journal: Circulation (2008)

P roperly designed and conducted randomized controlled clinical trials (RCTs) are the premier tool for both testing mechanistic hypotheses and critically ascertaining the risks and benefits of a therapy or strategy for clinical care.The sample size of a trial is mainly a function of the rates of its primary objectives and the presumed influence of the intervention.Trials focusing on a primary outcome variable that can be readily quantified in each subject, such as blood pressure or plasma cholesterol levels, require substantially fewer participants and shorter durations to determine whether their predefined measurement is altered compared with a morbidity and mortality trial.Trials designed to determine whether clinical prognosis is altered by an intervention depend on the proportion of patients experiencing the predefined adverse clinical event(s) and often require 100s-foldgreater patient-time exposures to test their primary hypothesis and provide even modest information about safety.These resource-intense morbidity and mortality trials are generally only performed when information from observational studies as well as smaller mechanistic and surrogate-outcomes RCTs are so highly supportive of a favorable outcome that they justify the effort.Despite this understandable stacking of the cards with the best available information, many of the morbidity and mortality trials conducted to test for a potential favorable impact of an intervention conclude by not supporting the prestudy hypothesis-generating data. 1 The lessons in humility offered by these neutral or negative outcomes trials underscore the importance of obtaining crucial risk-benefit data before widespread adoption of even an apparently favorable therapy.
Distal Colorectal Cancers with Microsatellite Instability (MSI) Display Distinct Gene Expression Profiles that Are Different from Proximal MSI Cancers
Authors: Toshiaki Watanabe, Takashi Kobunai, Etsuko Toda, Yoko Yamamoto, Takamitsu Kanazawa, Yoshihiro Kazama, Junichiro Tanaka, Toshiaki Tanaka, Tsuyosi Konishi, Yoshihiro Okayama, Yoshikazu Sugimoto, Toshinori Oka, Shin Sasaki, Tetsuichiro Muto, Hirokazu Nagawa
Journal: Cancer Research (2006)

Abstract Promoter methylation of the mismatch repair gene plays a key role in sporadic microsatellite instability (MSI) colorectal cancers. However, promoter methylation often occurs in proximal colon cancers, and molecular phenotypes underlying MSI cancers in distal colon have not been fully clarified. Our goal was to clarify the difference between MSI and microsatellite stability (MSS) cancers and, furthermore, to determine distinct characteristics of proximal and distal MSI cancers. By DNA microarray analysis of 84 cancers (33 MSI and 51 MSS), we identified discriminating genes (177 probe sets), which predicted MSI status with a high accuracy rate (97.6%). These genes were related to phenotypic characteristics of MSI cancers. Next, we identified 24 probe sets that were differentially expressed in proximal and distal MSI cancers. These genes included promoter methylation-mediated genes, whose expression was significantly down-regulated in proximal MSI cancers. Among discriminating genes between MSI and MSS, nine methylation-mediated genes showed down-regulation in MSI cancers. Of these, 7 (77.8%) showed down-regulation in proximal MSI cancers. Furthermore, methylation-specific PCR confirmed that frequency of hMLH1 promoter methylation was significantly higher in proximal MSI cancers (P = 0.0317). These results suggested that there is a difference between proximal and distal MSI cancers in methylation-mediated influence on gene silencing. In conclusion, using DNA microarray, we could distinguish MSI and MSS cancers. We also showed distinct characteristics of proximal and distal MSI cancers. The inactivation form of hMLH, per se, differed between proximal and distal MSI cancers. These results suggested that distal MSI cancers constitute a distinct subgroup of sporadic MSI cancers. (Cancer Res 2006; 66(20): 9804-8)
Activity and safety of crizotinib in patients with ALK-positive non-small-cell lung cancer: updated results from a phase 1 study
Authors: D Ross Camidge, Yung-Jue Bang, Eunice L Kwak, A John Iafrate, Marileila Varella-Garcia, Stephen B Fox, Gregory J Riely, Benjamin Solomon, Sai-Hong I Ou, Dong-Wan Kim, Ravi Salgia, Panagiotis Fidias, Jeffrey A Engelman, Leena Gandhi, Pasi A Jänne, Daniel B Costa, Geoffrey I Shapiro, Patricia LoRusso, Katherine Ruffner, Patricia Stephenson, Yiyun Tang, Keith Wilner, Jeffrey W Clark, Alice T Shaw
Journal: The Lancet Oncology (2012)
Regression of Peyer's patches in Galphai2 deficient mice prior to colitis is associated with reduced expression of Bcl-2 and increased apoptosis
Authors: L Ohman
Journal: Gut (2002)

<h3>ABSTRACT</h3> <h3>Objective</h3> To determine whether handheld widefield optical coherence tomography (OCT) can be used to document retinopathy of prematurity (ROP) stage while using scleral depression to improve peripheral views. <h3>Design</h3> Prospective observational study <h3>Participants</h3> Consecutive neonates admitted to the neonatal intensive care unit (NICU) in a single academic medical center who also met criteria for ROP screening and consented for research imaging. <h3>Methods</h3> Scleral depression was combined with widefield OCT using an investigational 400-kHz, 55-degree field of view handheld OCT during ROP screening from October 28, 2020 to March 03, 2021. <h3>Main Outcome Measures</h3> Acquisition of <i>en face</i> and B-scan imaging of the peripheral retina to objectively assess early vitreoretinal pathology, including the demarcation between vascularized and anterior avascular retina, the presence of early ridge formation, and small neovascular tufts. <h3>Results</h3> Various stages of ROP were detected using a rapid acquisition OCT system. In one neonate, serial OCT imaging over a five-week period demonstrated accumulation of neovascular tufts with progression to stage 3 ROP with extraretinal fibrovascular proliferation along the ridge. Videography of this technique is included in this report for instructional purposes. <h3>Conclusions</h3> Serial examinations using widefield OCT and scleral depression may improve detection and documentation of ROP disease progression. Earlier detection of ROP-related proliferation may prevent vitreoretinal traction, retinal detachment, and blindness.
Accuracy of an Unattended Home CPAP Titration in the Treatment of Obstructive Sleep Apnea
Authors: F. SÉRIÈS
Journal: American Journal of Respiratory and Critical Care Medicine (2000)

Treatment of sleep apnea–hypopnea syndrome (SAHS) by fixed continuous positive airway pressure (CPAP) requires an in-laboratory titration procedure to determine the effective pressure level (Peff ). We recently reported that one auto-CPAP machine can be used without titration study allowing Peff determination. The aim of this study was to evaluate the accuracy of an auto CPAP trial at home. A 1- or 2-wk automatic CPAP trial was done at home in 40 patients by estimating the reference pressure (Pref ) to be set and a Pref + 3 cm H2O/ − 4 cm H2O pressure interval. Peff was then determined according to the percentage of CPAP time that was spent ⩽ Pref. This Peff value was set on a fixed CPAP machine for two additional weeks and a control sleep study was done. The pressure setting on fixed CPAP had to be increased by 1 ± 1 cm H2O (mean ± SD) above estimated Pref. Sleep improved with fixed CPAP, with a normalization of the apnea + hypopnea index (AHI) in 38 of 40 and resumption of diurnal hypersomnolence. CPAP compliance remained excellent (CPAP use: 6.1 ± 1.7 h/ night) after 6.5 ± 2.8 mo of CPAP treatment. These results indicate that auto-CPAP therapy represents a new useful and accurate way to identify conventional CPAP setting outside hospital and sleep laboratories.