tbuckley/cabot-search huggingface dataset:
WHO Rapid Advice Guidelines for pharmacological management of sporadic human infection with avian influenza A (H5N1) virus
Authors: Holger J Schünemann, Suzanne R Hill, Meetali Kakad, Richard Bellamy, Timothy M Uyeki, Frederick G Hayden, Yazdan Yazdanpanah, John Beigel, Tawee Chotpitayasunondh, Chris Del Mar, Jeremy Farrar, Tran Tinh Hien, Bülent Özbay, Norio Sugaya, Keiji Fukuda, Nikki Shindo, Lauren Stockman, Gunn E Vist, Alice Croisier, Azim Nagjdaliyev, Cathy Roth, Gail Thomson, Howard Zucker, Andrew D Oxman
Journal: The Lancet Infectious Diseases (2006)
Maternal cardiac metabolism in pregnancy
Authors: L. X. Liu, Z. Arany
Journal: Cardiovascular Research (2014)

Pregnancy causes dramatic physiological changes in the expectant mother. The placenta, mostly foetal in origin, invades maternal uterine tissue early in pregnancy and unleashes a barrage of hormones and other factors. This foetal 'invasion' profoundly reprogrammes maternal physiology, affecting nearly every organ, including the heart and its metabolism. We briefly review here maternal systemic metabolic changes during pregnancy and cardiac metabolism in general. We then discuss changes in cardiac haemodynamic during pregnancy and review what is known about maternal cardiac metabolism during pregnancy. Lastly, we discuss cardiac diseases during pregnancy, including peripartum cardiomyopathy, and the potential contribution of aberrant cardiac metabolism to disease aetiology.
Epidemiology, management and prognosis of colorectal cancer with lung metastases: a 30-year population-based study
Authors: E. Mitry, B. Guiu, S. Cosconea, V. Jooste, J. Faivre, A.-M. Bouvier
Journal: Gut (2010)

<h3>Objective</h3> Epidemiological data on synchronous and metachronous lung metastases from colorectal cancer are scarce. The aim of this study was to determine trends in the incidence, treatment and survival in colorectal cancer with lung metastases in the general population. <h3>Design and patients</h3> All cases of lung metastases from colorectal cancer registered in the Burgundy digestive cancer registry between 1976 and 2005 were included. Trends in the incidence of synchronous colorectal cancer lung metastases were estimated. A Cox model was used to analyse the risk of developing a metachronous metastasis. Multivariate analyses were performed using a relative survival model with proportional hazard applied to the net survival by interval. <h3>Results</h3> Overall, 11.0% of patients had synchronous lung metastases. The frequency of synchronous lung metastases significantly increased for both sexes over time, with a nearly threefold increase between the periods 1976–1985 and 1996–2005. The overall 5-year cumulative risk of developing metachronous lung metastases was 5.8%. It did not significantly vary with time. Compared to colon cancer, rectal cancers had a higher risk of developing synchronous (OR: 2.80 (1.65–4.76)) and metachronous (OR: 2.63 (1.69–4.08)) lung metastases. Overall, 4.1% of synchronous lung metastases and 14.3% of metachronous lung metastases were resected for cure. The 3-year relative survival was 11.3% for synchronous lung metastases and 13.8% for metachronous lung metastases. It was, respectively, 53.0% and 59.2% after resection for cure. In multivariate analysis, the relative risk of death for the 1996–2005 period was about one fifth of that for the 1976–1985 period. <h3>Conclusions</h3> The incidence of synchronous lung metastases increased over time, whereas the incidence of metachronous lung metastases remained stable. Lung metastases were more frequent in rectal cancer than in colon cancer. Unless surgical resection is possible, the prognosis for lung metastases remains very poor.
Diagnostic Relevance of Clonal Cytogenetic Aberrations in Malignant Soft-Tissue Tumors
Authors: Jonathan A. Fletcher, Harry P. Kozakewich, Fredric A. Hoffer, Janice M. Lage, Noel Weidner, Robert Tepper, Geraldine S. Pinkus, Cynthia C. Morton, Joseph M. Corson
Journal: New England Journal of Medicine (1991)

Malignant soft-tissue tumors often present substantial diagnostic challenges. Chromosome aberrations that might be diagnostic have been identified in some types of soft-tissue tumors, but the overall frequency and diagnostic relevance of these aberrations have not been established.
Lumbar spine region pathology and hamstring and calf injuries in athletes: is there a connection?
Authors: J W Orchard, P Farhart, C Leopold
Journal: British Journal of Sports Medicine (2004)

This paper discusses the theory that subtle lumbosacral canal impingement of the L5 nerve root may be a relatively common occurrence in older footballers and may in fact be a common underlying basis for the age related predisposition towards hamstring and calf strains.
Use of high potency statins and rates of admission for acute kidney injury: multicenter, retrospective observational analysis of administrative databases
Authors: C. R. Dormuth, B. R. Hemmelgarn, J. M. Paterson, M. T. James, G. F. Teare, C. B. Raymond, J.-P. Lafrance, A. Levy, A. X. Garg, P. Ernst
Journal: BMJ (2013)

<b>Objective</b> To quantify an association between acute kidney injury and use of high potency statins versus low potency statins. <b>Design</b> Retrospective observational analysis of administrative databases, using nine population based cohort studies and meta-analysis. We performed as treated analyses in each database with a nested case-control design. Rate ratios for different durations of current and past statin exposure to high potency or low potency statins were estimated using conditional logistic regression. Ratios were adjusted for confounding by high dimensional propensity scores. Meta-analytic methods estimated overall effects across participating sites. <b>Setting</b> Seven Canadian provinces and two databases in the United Kingdom and the United States. <b>Participants</b> 2 067 639 patients aged 40 years or older and newly treated with statins between 1 January 1997 and 30 April 2008. Each person hospitalized for acute kidney injury was matched with ten controls. <b>Intervention</b> A dispensing event was new if no cholesterol lowering drug or niacin prescription was dispensed in the previous year. High potency statin treatment was defined as ≥10 mg rosuvastatin, ≥20 mg atorvastatin, and ≥40 mg simvastatin; all other statin treatments were defined as low potency. Statin potency groups were further divided into cohorts with or without chronic kidney disease. <b>Main outcome measure</b> Relative hospitalization rates for acute kidney injury. <b>Results</b> Of more than two million statin users (2 008 003 with non-chronic kidney disease; 59 636 with chronic kidney disease), patients with similar propensity scores were comparable on measured characteristics. Within 120 days of current treatment, there were 4691 hospitalizations for acute kidney injury in patients with non-chronic kidney injury, and 1896 hospitalizations in those with chronic kidney injury. In patients with non-chronic kidney disease, current users of high potency statins were 34% more likely to be hospitalized with acute kidney injury within 120 days after starting treatment (fixed effect rate ratio 1.34, 95% confidence interval 1.25 to 1.43). Users of high potency statins with chronic kidney disease did not have as large an increase in admission rate (1.10, 0.99 to 1.23). χ<sup>2</sup> tests for heterogeneity confirmed that the observed association was robust across participating sites. <b>Conclusions</b> Use of high potency statins is associated with an increased rate of diagnosis for acute kidney injury in hospital admissions compared with low potency statins. The effect seems to be strongest in the first 120 days after initiation of statin treatment.
Persistent Methicillin-resistant <i>Staphylococcus aureus</i> and Rate of FEV<sub>1</sub> Decline in Cystic Fibrosis
Authors: Elliott C. Dasenbrook, Christian A. Merlo, Marie Diener-West, Noah Lechtzin, Michael P. Boyle
Journal: American Journal of Respiratory and Critical Care Medicine (2008)

Rationale: The prevalence in cystic fibrosis (CF) of respiratory cultures with methicillin-resistant Staphylococcus aureus (MRSA) has dramatically increased over the last 10 years, but the effect of MRSA on FEV1 decline in CF is unknown.Objectives: To determine the association between MRSA respiratory infection and FEV1 decline in children and adults with CF.Methods: This was a 10-year cohort study using the Cystic Fibrosis Foundation patient registry from 1996–2005. We studied individuals who developed new MRSA respiratory tract infection. Repeated-measures regression was used to assess the association between MRSA and FEV1 decline, adjusted for confounders, in individuals aged 8–21 years and adults (aged 22–45 yr). Two different statistical models were used to assess robustness of results.Measurements and Main Results: The study cohort included 17,357 patients with an average follow-up of 5.3 years. During the study period, 1,732 individuals developed new persistent MRSA infection (≥3 MRSA cultures; average, 6.8 positive cultures) and were subsequently followed for an average of 3.5 years. Even after adjustment for confounders, rate of FEV1 decline in individuals aged 8–21 years with persistent MRSA was more rapid in both statistical models. Their average FEV1 decline of 2.06% predicted/year was 43% more rapid than the 1.44% predicted/year in those without MRSA (difference, −0.62% predicted/yr; 95% confidence interval, −0.70 to −0.54; P < 0.001). Effect of MRSA on FEV1 decline in adults was not clinically significant.Conclusions: Persistent infection with MRSA in individuals with CF between the ages of 8 and 21 years is associated with a more rapid rate of decline in lung function.
Tumor Hypoxia Predicts Biochemical Failure following Radiotherapy for Clinically Localized Prostate Cancer
Authors: Michael Milosevic, Padraig Warde, Cynthia Ménard, Peter Chung, Ants Toi, Adrian Ishkanian, Michael McLean, Melania Pintilie, Jenna Sykes, Mary Gospodarowicz, Charles Catton, Richard P. Hill, Robert Bristow
Journal: Clinical Cancer Research (2012)

Abstract Purpose: Tumor hypoxia is an important determinant of outcome in many human malignancies and is associated with treatment resistance and metastases. The aim of this study was to determine the effect of hypoxia in patients with prostate cancer treated with radiotherapy. Experimental Design: Tumor hypoxia was measured in 247 patients with clinically localized prostate cancer before radiotherapy, with or without hormonal therapy. The median pO2 was 6.8 mm Hg and the median hypoxic percentage less than 10 mm Hg (HP10) was 63%. The median follow-up was 6.6 years. Results: The 5-year biochemical relapse-free rate (bRFR) was 78%. Prostrate-specific antigen and Gleason score were both associated with biochemical relapse and formed a baseline clinical model. The effect of hypoxia was found to vary with the duration of patient follow-up. HP10, when added to the clinical model, was an independent predictor of early bRFR (P = 0.019). The relationship between hypoxia and early bRFR was more pronounced when the analysis was restricted to 142 patients with bulk tumor at the site of the oxygen measurements (P = 0.004). Hypoxia was the only factor predictive of local recurrence in 70 patients who had biopsies conducted during follow-up (P = 0.043), again with the effect being greatest early after completing treatment. Conclusions: This is the largest clinical study of prostate cancer hypoxia with direct measurement of tumor oxygen levels. It shows that hypoxia is associated with early biochemical relapse after radiotherapy and also with local recurrence in the prostate gland. Clin Cancer Res; 18(7); 2108–14. ©2012 AACR.
Evaluation of Patients With Suspected Acute Pulmonary Embolism: Best Practice Advice From the Clinical Guidelines Committee of the American College of Physicians
Authors: Ali S. Raja, Jeffrey O. Greenberg, Amir Qaseem, Thomas D. Denberg, Nick Fitterman, Jeremiah D. Schuur
Journal: Annals of Internal Medicine (2015)

Pulmonary embolism (PE) can be a severe disease and is difficult to diagnose, given its nonspecific signs and symptoms. Because of this, testing patients with suspected acute PE has increased dramatically. However, the overuse of some tests, particularly computed tomography (CT) and plasma d-dimer measurement, may not improve care while potentially leading to patient harm and unnecessary expense.The literature search encompassed studies indexed by MEDLINE (1966-2014; English-language only) and included all clinical trials and meta-analyses on diagnostic strategies, decision rules, laboratory tests, and imaging studies for the diagnosis of PE. This document is not based on a formal systematic review, but instead seeks to provide practical advice based on the best available evidence and recent guidelines. The target audience for this paper is all clinicians; the target patient population is all adults, both inpatient and outpatient, suspected of having acute PE.Clinicians should use validated clinical prediction rules to estimate pretest probability in patients in whom acute PE is being considered.Clinicians should not obtain d-dimer measurements or imaging studies in patients with a low pretest probability of PE and who meet all Pulmonary Embolism Rule-Out Criteria.Clinicians should obtain a high-sensitivity d-dimer measurement as the initial diagnostic test in patients who have an intermediate pretest probability of PE or in patients with low pretest probability of PE who do not meet all Pulmonary Embolism Rule-Out Criteria. Clinicians should not use imaging studies as the initial test in patients who have a low or intermediate pretest probability of PE.Clinicians should use age-adjusted d-dimer thresholds (age × 10 ng/mL rather than a generic 500 ng/mL) in patients older than 50 years to determine whether imaging is warranted.Clinicians should not obtain any imaging studies in patients with a d-dimer level below the age-adjusted cutoff.Clinicians should obtain imaging with CT pulmonary angiography (CTPA) in patients with high pretest probability of PE. Clinicians should reserve ventilation-perfusion scans for patients who have a contraindication to CTPA or if CTPA is not available. Clinicians should not obtain a d-dimer measurement in patients with a high pretest probability of PE.
Gold Nanoshelled Liquid Perfluorocarbon Magnetic Nanocapsules: a Nanotheranostic Platform for Bimodal Ultrasound/Magnetic Resonance Imaging Guided Photothermal Tumor Ablation
Authors: Hengte Ke, Jinrui Wang, Sheng Tong, Yushen Jin, Shumin Wang, Enze Qu, Gang Bao, Zhifei Dai
Journal: Theranostics (2014)

Imaging guided ablation therapy has been applied in both biomedical research and clinical trials and turned out to be one of the most promising approaches for cancer treatment. Herein, the multifunctional nanocapsules were fabricated through loading perfluorooctylbromide (PFOB) and superparamagnetic iron oxide nanoparticles (SPIOs) into poly(lactic acid) (PLA) nanocapsules (NCs), followed by the formation of PEGylated gold nanoshell on the surface. The resulting multi-component NCs were proved to be able to act as nanotheranostic agent to achieve successful bimodal ultrasound (US)/magnetic resonance imaging (MRI) guided photothermal ablation in human tumor xenograft models non-invasively. Such a single theranostic agent with the combination of real-time US and high-resolution MR imaging would be of great value to offer more comprehensive diagnostic information and dynamics of disease progression for the accurate location of therapeutic focusing spot in the targeted tumor tissue, showing great potential as an effective nanoplatform for contrast imaging guided photothermal therapy.
Instrument-, age- and site-dependent variations of dermoscopic patterns of congenital melanocytic naevi: a multicentre study
Authors: S. Seidenari, G. Pellacani, A. Martella, F. Giusti, G. Argenziano, P. Buccini, P. Carli, C. Catricalà, V. De Giorgi, A. Ferrari, V. Ingordo, A.M. Manganoni, K. Peris, D. Piccolo, M.A. Pizzichetta
Journal: British Journal of Dermatology (2006)

Background Recently, we identified and described dermoscopic aspects, present with a higher frequency in congenital melanocytic lesions with respect to acquired naevi. We also classified small- and medium-sized congenital naevi (CN) into nine subtypes according to their macroscopic and dermoscopic aspects. Objectives Because the recognition of dermoscopic features may be instrument dependent, in this study, we wanted to check whether dermoscopic patterns specific for CN can be identified in digital images acquired by means of different instruments. We also wanted to check the validity of our previously proposed classification and assess possible age- and site-dependent variations of dermoscopic patterns and naevus subtypes. Patients/methods Images corresponding to 384 small- or medium-sized CN were collected in eight different centres employing four different instruments. Lesion images were evaluated and checked for the presence of specific dermoscopic criteria, classified, and compared with a database of 350 acquired naevi. Results Specific and unspecific dermoscopic features were identifiable in images acquired by means of all four instrument types. The mean number of identified features per lesion did not vary according to the instrument employed for the acquisition of the images; however, it was lower for lesions recorded employing low magnifications. The previously proposed classification was easily applied to the whole image database. The variegated naevus type was identified as a highly specific clinical/dermoscopic pattern. Dermoscopic features varied according to age and location. The globular type prevailed in subjects under 11 years of age and on the trunk, whereas the majority of reticular lesions were located on the limbs. Conclusions Because definite clinical and histological criteria for the diagnosis of the congenital nature of naevi are lacking, the use of dermoscopy can be of great help in identifying those lesions where the presence of specific dermoscopic features makes the diagnosis of CN more likely. Moreover, dermoscopy can be useful both for the classification of lesions already identified as congenital according to definite clinical and anamnestic data and for a possible correlation of naevus phenotype and dermoscopic patterns to the risk of developing a malignant melanoma in prospective studies.
Mitigating nuclear disaster
Authors: P. Sims, D. Josephs
Journal: BMJ (1985)

<h3>Abstract</h3> <h3>Purpose of review:</h3> To present emerging issues in neurometabolic disorders, with an emphasis on the diagnostic workup of patients with suspected neurometabolic disorders and some future challenges in the care for these patients. <h3>Recent findings:</h3> Next-generation sequencing and next-generation metabolic screening increase the speed and yield of the diagnostic process in neurometabolic disorders. Furthermore, they deepen our insights into the underlying disease mechanisms. Care of adult patients with neurometabolic disorders is an expanding subspecialty, especially in internal medicine and neurology. <h3>Summary:</h3> We briefly discuss some novel genetic and biochemical laboratory techniques and changing insights in the molecular basis of disease, and illustrate the importance of MRI pattern recognition in the diagnostic process. Furthermore, we discuss gene therapy that is cautiously entering the field, and pay attention to the new field of (transition of) care for adult patients with inborn errors of metabolism.
Ablation of Cardiac Myosin-Binding Protein-C Accelerates Stretch Activation in Murine Skinned Myocardium
Authors: Julian E. Stelzer, Sandy B. Dunning, Richard L. Moss
Journal: Circulation Research (2006)

Cardiac myosin binding protein-C (cMyBP-C) is a thick filament accessory protein that binds tightly to myosin, but despite evidence that mutations in the cMyBP-C gene comprise a frequent cause of hypertrophic cardiomyopathy, relatively little is known about the role(s) of cMyBP-C in myocardium. Based on earlier studies demonstrating the potential importance of stretch activation in cardiac contraction, we examined the effects of cMyBP-C on the stretch activation responses of skinned ventricular preparations from wild-type (WT) and homozygous cMyBP-C knockout mice (cMyBP-C(-/-)) previously developed in our laboratory. Sudden stretch of skinned myocardium during maximal or submaximal Ca2+ activations resulted in an instantaneous increase in force that quickly decayed to a minimum and was followed by a delayed redevelopment of force (ie, stretch activation) to levels greater than prestretch force. Ablation of cMyBP-C dramatically altered the stretch activation response, ie, the rates of force decay and delayed force transient were accelerated compared with WT myocardium. These results suggest that cMyBP-C normally constrains the spatial position of myosin cross-bridges, which, in turn, limits both the rate and extent of interaction of cross-bridges with actin. We propose that ablation of cMyBP-C removes this constraint, increases the likelihood of cross-bridge binding to actin, and speeds the rate of delayed force development following stretch. Regardless of the specific mechanism, acceleration of cross-bridge cycling in cMyBP-C(-/-) myocardium could account for the abbreviation of systolic ejection in this mouse as a direct consequence of premature stretch activation of ventricular myocardium.
Effect on Tumor Cells of Blocking Survival Response to Glucose Deprivation
Authors: H.-R. Park, A. Tomida, S. Sato, Y. Tsukumo, J. Yun, T. Yamori, Y. Hayakawa, T. Tsuruo, K. Shin-ya
Journal: JNCI Journal of the National Cancer Institute (2004)

Background: Glucose deprivation, a feature of poorly vascularized solid tumors, activates the unfolded protein response (UPR), a stress-signaling pathway, in tumor cells. We recently isolated a novel macrocyclic compound, versipelostatin (VST), that inhibits transcription from the promoter of GRP78, a gene that is activated as part of the UPR. We examined the effect of VST on the UPR induced by glucose deprivation or other stressors and on tumor growth in vivo. Methods: Human colon cancer HT-29, fibrosarcoma HT1080, and stomach cancer MKN74 cells were cultured in the absence of glucose or in the presence of glucose and a UPR-inducing chemical stressor (the N -glycosylation inhibitor tunicamycin, the calcium ionophore A23187, or the hypoglycemia-mimicking agent 2-deoxyglucose [2DG]). The effect of VST on UPR induction was determined by reverse transcription–polymerase chain reaction and immunoblot analysis of the UPR target genes GRP78 and GRP94; by immunoblot analysis of the UPR transcriptional activators ATF6, XBP1, and ATF4; and by analyzing reporter gene expression in cells transiently transfected with a GRP78 promoter–reporter gene. Cell sensitivity to VST was examined with a colony formation assay and flow cytometry. In vivo antitumor activity of VST was assessed with an MKN74 xenograft model. Results: VST inhibited expression of UPR target genes in glucose-deprived or 2DG-treated cells but not in cells treated with tunicamycin or A23187. VST also inhibited the production of the UPR transcriptional activators XBP1 and ATF4 during glucose deprivation. The UPR-inhibitory action of VST was seen only in conditions of glucose deprivation and caused selective and massive killing of the glucose-deprived cells. VST alone and in combination with cisplatin statistically significantly ( P = .004 and P <.001 for comparisons with untreated control, respectively) inhibited tumor growth of MKN74 xenografts. Conclusion: Disruption of the UPR may provide a novel therapeutic approach to targeting glucose-deprived solid tumors.