tbuckley/cabot-search huggingface dataset:
Translating Evidence into Population Health Improvement: Strategies and Barriers
Authors: Steven H. Woolf, Jason Q. Purnell, Sarah M. Simon, Emily B. Zimmerman, Gabriela J. Camberos, Amber Haley, Robert P. Fields
Journal: Annual Review of Public Health (2015)

Among the challenges facing research translation-the effort to move evidence into policy and practice-is that key questions chosen by investigators and funders may not always align with the information priorities of decision makers, nor are the findings always presented in a form that is useful for or relevant to the decisions at hand. This disconnect is a problem particularly for population health, where the change agents who can make the biggest difference in improving health behaviors and social and environmental conditions are generally nonscientists outside of the health professions. To persuade an audience that does not read scientific journals, strong science may not be enough to elicit change. Achieving influence in population health often requires four ingredients for success: research that is responsive to user needs, an understanding of the decision-making environment, effective stakeholder engagement, and strategic communication. This article reviews the principles and provides examples from a national and local initiative.
Primary Mediastinal Large B-Cell Lymphoma With Sclerosis in Pediatric and Adolescent Patients: Treatment and Results From Three Therapeutic Studies of the Berlin-Frankfurt-Münster Group
Authors: K. Seidemann, M. Tiemann, I. Lauterbach, G. Mann, I. Simonitsch, K. Stankewitz, M. Schrappe, M. Zimmermann, C. Niemeyer, R. Parwaresch, H. Riehm, A. Reiter
Journal: Journal of Clinical Oncology (2003)

Primary mediastinal large B-cell lymphoma with sclerosis (PMLBL) is a rare entity of non-Hodgkin's lymphoma (NHL) arising from thymic mature B cells. Optimal treatment strategies remain to be established, especially in pediatric patients.This study analyzes clinical characteristics and treatment outcome of 30 pediatric patients with PMLBL, diagnosed in multicenter therapy NHL-Berlin-Frankfurt-Münster Group (BFM) trials. Treatment was stratified by stage and serum lactate dehydrogenase (LDH) and consisted of four to six 5-day courses of chemotherapy using steroids, oxazaphosphorine alkylating agents, methotrexate, cytarabine, etoposide, and doxorubicin. Radiation was not part of the protocol.From April 1986 to August 1999, 1,650 patients with newly diagnosed NHL were enrolled in the NHL-BFM trials; 30 patients (1.8%) had PMLBL. Median age was 14.3 years (range, 1.4 to 16.7 years); 15 patients were male and 15 patients were female. With a median observation time of 5 years (range, 1 to 12 years), probability of event-free survival (pEFS) at 5 years was 0.70 (SE, 0.08). Two patients erroneously diagnosed as T-cell NHL received non-B-cell therapy and died from progress of disease. Events in 28 patients receiving B-cell therapy included early progress during therapy (n = 1) and relapse (n = 6). Residual mediastinal masses were present in 23 patients after two courses of therapy and in 15 patients after the end of therapy. LDH > or = 500 U/L was associated with increased risk of failure in multivariate analysis.PMLBL mainly is found in adolescents. Dose-intense chemotherapy including high-dose methotrexate yields a pEFS at 5 years of 0.70 (SE, 0.08). LDH is of prognostic value in pediatric patients with PMLBL.
Studies of amiodarone during experimental myocardial infarction: beneficial effects on hemodynamics and infarct size.
Authors: L W DeBoer, J J Nosta, R A Kloner, E Braunwald
Journal: Circulation (1982)

The effect of amiodarone was investigated in a canine model of myocardial infarction. The left anterior descending coronary artery was occluded in 24 anesthetized dogs. After 15 minutes of coronary artery occlusion, the ischemic myocardium at risk of necrosis was determined by labeling the heart with technetium-99m-labeled human albumin microspheres injected into the systemic circulation through the left atrium, and the dogs were than randomized to either a saline-treated control group (n = 13) or an amiodarone-treated group (n = 11) that received i.v. amiodarone, 10 mg/kg, administered in a single bolus 30 minutes after coronary artery occlusion. Myocardial infarct size was determined directly after 6 hours of coronary occlusion by incubation of sections of myocardium in triphenyltetrazolium chloride, a dehydrogenase stain, and expressed as a percentage of left ventricle below occlusion. Autoradiography of the stained myocardial sections was performed to determine the ischemic myocardium at risk of necrosis, which was similar in the control and amiodarone-treated groups (31.8 +/- 2.8% vs 32.5 +/- 3.3% of the left ventricle, respectively). In the amiodarone-treated group, only 67.1 +/- 8.4% of the myocardium at risk became necrotic; in the control group, 97.5 +/- 7.7% of the myocardium at risk became necrotic (p less than 0.01), representing 21.8 +/- 3.5% vs 31.1 +/- 2.8% of the left ventricle below occlusion, respectively (p less than 0.025). Amiodarone decreased heart rate, contractility and afterload. Its beneficial action on infarct size is related presumably to reduced myocardial oxygen demand.
Loss-of-function variants in endothelial lipase are a cause of elevated HDL cholesterol in humans
Authors: Andrew C. Edmondson, Robert J. Brown, Sekar Kathiresan, L. Adrienne Cupples, Serkalem Demissie, Alisa Knodle Manning, Majken K. Jensen, Eric B. Rimm, Jian Wang, Amrith Rodrigues, Vaneeta Bamba, Sumeet A. Khetarpal, Megan L. Wolfe, Stephanie DerOhannessian, Mingyao Li, Muredach P. Reilly, Jens Aberle, David Evans, Robert A. Hegele, Daniel J. Rader
Journal: Journal of Clinical Investigation (2009)

Elevated plasma concentrations of HDL cholesterol (HDL-C) are associated with protection from atherosclerotic cardiovascular disease. Animal models indicate that decreased expression of endothelial lipase (LIPG) is inversely associated with HDL-C levels, and genome-wide association studies have identified LIPG variants as being associated with HDL-C levels in humans. We hypothesized that loss-of-function mutations in LIPG may result in elevated HDL-C and therefore performed deep resequencing of LIPG exons in cases with elevated HDL-C levels and controls with decreased HDL-C levels. We identified a significant excess of nonsynonymous LIPG variants unique to cases with elevated HDL-C. In vitro lipase activity assays demonstrated that these variants significantly decreased endothelial lipase activity. In addition, a meta-analysis across 5 cohorts demonstrated that the low-frequency Asn396Ser variant is significantly associated with increased HDL-C, while the common Thr111Ile variant is not. Functional analysis confirmed that the Asn396Ser variant has significantly decreased lipase activity both in vitro and in vivo, while the Thr111Ile variant has normal lipase activity. Our results establish that loss-of-function mutations in LIPG lead to increased HDL-C levels and support the idea that inhibition of endothelial lipase may be an effective mechanism to raise HDL-C.
Histology predicts cirrhotic evolution of post transplant hepatitis C
Authors: M Guido
Journal: Gut (2002)

Background: Hepatitis C recurring after orthotopic liver transplantation varies in severity and some patients rapidly develop fully established liver cirrhosis. Neither clinical nor biological markers of such rapid cirrhotic evolution are available. Aim: To assess the value of histology in identifying patients who will develop cirrhosis shortly after liver transplantation. Patients and methods: Only cases of recurrent hepatitis C diagnosed by both hepatitis C virus-RNA positive serum and liver changes consistent with hepatitis, with no other causes of allograft injury, were considered. A total of 128 liver biopsies were scored from 29 consecutive patients with a mean follow up of 48 (13.97) months. The histological activity index was evaluated according to Ishak <i>et al</i>. The time of the first histological diagnosis of recurrent hepatitis C in the absence of rejection was defined as time of histological recurrence (RHC-T). Results: First histological diagnosis of recurrent hepatitis with no features of rejection was obtained at the six month biopsy in 23 of 29 cases. By the end of follow up, nine patients had developed cirrhosis (mean follow up 38 (14.39) months (range 18–60)). The remainder (mean follow up 46 (13.40) months (24–72)) showed a spectrum of fibrosis but no cirrhosis. Severe necroinflammatory lesions at RHC-T significantly correlated with rapid development of cirrhosis. At the RHC-T biopsy, only cases evolving into cirrhosis showed confluent necrosis. The median value of the histological activity index was 11 (mean 11.11 (1.76) (range 9–14)) in patients who developed cirrhosis and four (mean 4 (1.78) (range 1–8)) in the others (p&lt;0.0001). A histological activity index ≥9 was associated with rapid development of cirrhosis in 100% of cases. Conclusions: After liver transplantation, the histological activity of recurrent hepatitis C predicts the risk of development of cirrhosis. By adopting Ishak9s scoring system, a histological activity index ≥9 was 100% sensitive/specific in identifying subjects who rapidly developed cirrhosis.
Ikaros Modulates Cholesterol Uptake: A Link between Tumor Suppression and Differentiation
Authors: Siobhan Loeper, Sylvia L. Asa, Shereen Ezzat
Journal: Cancer Research (2008)

Abstract Ikaros is a transcription factor that directs lymphoid lineage commitment and pituitary neuroendocrine cell expansion and function. Here, we show that Ikaros regulates the low-density lipoprotein receptor (LDL-R) to alter metabolism in pituitary corticotroph cells. The DNA-binding Ikaros isoform Ik1 binds and enhances activity of the LDL-R promoter. Ik1 decreases methylation and increases acetylation of histone H3 (Lys9) at the LDL-R promoter. Confocal microscopy and quantitative fluorometry show enhanced LDL endocytosis in Ik1-transfected cells that exhibit abundant endoplasmic reticulum, large Golgi complexes, and prominent secretory granule formation, consistent with more robust cholesterol incorporation into functionally relevant membrane-rich organelles. Consistent with these data, LDL-R−/− mice, like Ik−/− mice, have decreased circulating levels of adrenocorticotropic hormone. These findings expand the repertoire of Ikaros actions to include regulation of the cholesterol uptake metabolic pathway with therapeutic implications for lipid-modifying drugs in Ikaros-associated cancers. [Cancer Res 2008;68(10):3715–23]
Human Prostate Cancer in a Clinically Relevant Xenograft Mouse Model: Identification of β(1,6)-Branched Oligosaccharides as a Marker of Tumor Progression
Authors: Tobias Lange, Sebastian Ullrich, Imke Müller, Michael F. Nentwich, Katrin Stübke, Susanne Feldhaus, Christine Knies, Olaf J.C. Hellwinkel, Robert L. Vessella, Claudia Abramjuk, Mario Anders, Jennifer Schröder-Schwarz, Thorsten Schlomm, Hartwig Huland, Guido Sauter, Udo Schumacher
Journal: Clinical Cancer Research (2012)

To establish xenograft mouse models of metastatic and nonmetastatic human prostate cancer and to apply these models to the search for aberrant glycosylation patterns associated with tumor progression in vivo and in patients.Prostate cancer cells (LNCaP, PC-3, LuCaP 23.1, and DU-145) were xenografted subcutaneously into immunodeficient pfp(-/-)/rag2(-/-) mice. Tumor growth and metastasis formation were quantified and as altered glycosylation patterns have been associated with metastasis formation in several other malignancies, prostate cancer cells were profiled by a quantitative real-time PCR (qRT-PCR) glycosylation array and compared with normal human prostate cells. The activity of upregulated glycosyltransferases was analyzed by their sugar residues end products using lectin histochemistry on primary tumors and metastases in the animal experiments and on 2,085 clinical samples.PC-3 cells produced the largest number of spontaneous lung metastases, followed by LNCaP and LuCaP 23.1, whereas DU-145 was nonmetastatic. qRT-PCR revealed an upregulation of β1,6-N-acetylglucosaminyltransferase-5b (Mgat5b) in all prostate cancer cell lines. Mgat5b products [β(1,6)-branched oligosaccharides] were predominantly detectable in metastatic xenografts as shown by increased binding of Phaseolus vulgaris leukoagglutinin (PHA-L). The percentage of prostate cancer patients who were PHA-L positive was 86.5. PHA-L intensity correlated with serum prostate-specific antigen and a cytoplasmic staining negatively affected disease-free survival.We show a novel xenograft mouse model for human prostate cancer respecting the complete metastatic cascade. Specific glycosylation patterns reveal Mgat5b products as relevant markers of both metastatic competence in mice and disease-free survival in patients. This is the first description of Mgat5b in prostate cancer indicating a significant biologic importance of β(1,6)-branched oligosaccharides for prostate cancer progression.
Mechanics of intercostal space and actions of external and internal intercostal muscles.
Authors: A De Troyer, S Kelly, P T Macklem, W A Zin
Journal: Journal of Clinical Investigation (1985)

It is conventionally considered that because of their fiber orientations, the external intercostal muscles elevate the ribs, whereas the internal interosseous intercostals lower the ribs. The mechanical action of the intercostal muscles, however, has never been studied directly, and the electromyographic observations supporting this conventional thinking must be interpreted with caution. In the present studies, the external and internal interosseous intercostal muscles have been separately stimulated in different interspaces at, above, and below end-expiratory rib cage volume in anesthetized dogs. The axial (cephalo-caudal) displacements of the ribs were measured using linear displacement transducers. The results indicate that when contracting in a single interspace and other muscles are relaxed, both the external and internal intercostals have a net rib elevating action at end-expiratory rib cage volume. This action increases as rib cage volume decreases, but it progressively decreases as rib cage volume increases such that at high rib cage volumes, both the external and internal intercostals lower the ribs. Stimulating the intercostal muscles in three adjacent intercostal spaces simultaneously produced similar directional rib motion results. We conclude that (a) in contrast with the conventional thinking, the external and internal interosseous intercostals acting alone have by and large a similar effect on the ribs into which they insert; (b) this effect is very much dependent on rib cage (lung) volume; and (c) intercostal muscle action is primarily determined by the resistance of the upper ribs to caudad displacement relative to the resistance of the lower ribs to cephalad displacement. The lateral intercostals, however, might be more involved in postural movements than in respiration. Their primary involvement in rotations of the trunk might account for the presence of two differently oriented muscle layers between the ribs.
Fetuin-A Levels Are Increased in Patients With Type 2 Diabetes and Peripheral Arterial Disease
Authors: David Peter Lorant, Milan Grujicic, Clemens Hoebaus, Johanna-Maria Brix, Florian Hoellerl, Guntram Schernthaner, Renate Koppensteiner, Gerit-Holger Schernthaner
Journal: Diabetes Care (2010)

Low levels of fetuin-A, a systemic calcification inhibitor, are linked to mortality in patients on dialysis. In contrast, elevated fetuin-A is associated with cardiovascular events in non-renal patients. We investigated fetuin-A in patients with type 2 diabetes and peripheral arterial disease (PAD).We studied fetuin-A in 76 patients with PAD and normal glucose metabolism (NGM-PAD) and in 129 patients with PAD and type 2 diabetes (type 2 diabetes-PAD). Additionally, 40 patients with diabetes without any complications (type 2 diabetes-non-PAD) were examined.Type 2 diabetes-PAD subjects (399 ± 155 μg/ml) had significantly higher fetuin-A levels than type 2 diabetes-non-PAD subjects (247 ± 42; P < 0.001). In NGM-PAD subjects (376 ± 144), fetuin-A was significantly higher than in type 2 diabetes-non-PAD subjects (P < 0.001). Type 2 diabetes-PAD patients with mediasclerosis had lower fetuin-A than subjects without (P < 0.03). Regression analysis in type 2 diabetes-PAD subjects revealed that glycated A1C (P < 0.001) and mediasclerosis (P = 0.004) were the strongest predictors of fetuin-A. Multivariate regression revealed that a 1-SD increase in fetuin-A was associated with an odds ratio (OR) of 2.1 (95% CI 1.1-3.3; P < 0.001) for the prevalence of PAD and an OR of 1.4 (1.0-1.7, P = 0.039) for the prevalence of myocardial infarction.In contrast to previous findings, fetuin-A was higher in type 2 diabetes-PAD patients than in type 2 diabetes-non-PAD patients. In NGM-PAD patients, fetuin-A was also higher than in type 2 diabetes-non-PAD patients. In type 2 diabetes-PAD patients, fetuin-A was inversely associated with mediasclerosis-the calcification process pathognomonic for diabetic PAD. This association persisted in multivariate regression, which is in line with the calcification inhibition in coronary heart or renal disease.
Perfluorocarbon Liquid in the Management of Retinal Detachment with Proliferative Vitreoretinopathy
Authors: Gustavo E. Coll, Stanley Chang, Jennifer Sun, Mark R. Wieland, Maria H. Berrocal
Journal: Ophthalmology (1995)

To describe the techniques and results of perfluoro-N-octane used during vitrectomy for managing retinal detachment with severe proliferative vitreoretinopathy (PVR).The authors retrospectively studied 223 consecutive patients who underwent vitreoretinal surgery for severe PVR (93% D1-D3). Patients underwent an average of 1.72 prior vitreoretinal surgeries. Perfluoro-N-octane was used intraoperatively to flatten the retina, avoiding posterior drainage retinotomy, to identify areas of residual retinal traction and periretinal membranes, to stabilize the peripheral retina during dissection of anterior PVR, and to help determine the extent and location of relaxing retinotomies. Extended-term gas tamponade was used in 91% of eyes. All patients were followed for a minimum of 6 months.Seventy-eight percent of the retinas were reattached posterior to the scleral buckle after a single vitreoretinal surgery and 96% were reattached after multiple surgeries. An average of 1.24 vitrectomy surgeries were required. The final visual acuity was 20/400 or better in 74% of eyes and 20/80 or better in 30% (P = 0.004). Preoperative hypotony (intraocular pressure < or = 5 mmHg) and multiple prior vitreoretinal surgeries were associated with a poor final visual acuity (P = 0.01 and 0.02, respectively). Preoperative hypotony (intraocular pressure < or = 5 mmHg) was associated with a greater frequency of relaxing retinotomies (P = 0.02). Retained perfluoro-N-octane was observed postoperatively in the vitreous cavity in 1.3% and subretinal perfluoro-N-octane in 0.9%.Experience with perfluoro-N-octane has demonstrated its usefulness both diagnostically and therapeutically as an intraoperative tool and improved the anatomic and visual outcome for retinal detachment complicated by severe PVR.
Phenotypic Variability Associated with the D226N Allele of IMPDH1
Authors: Shahbaz Ali, Shahid Y. Khan, Muhammad Asif Naeem, Shaheen N. Khan, Tayyab Husnain, Saima Riazuddin, Radha Ayyagari, Sheikh Riazuddin, J. Fielding Hejtmancik, S. Amer Riazuddin
Journal: Ophthalmology (2014)
Two visual systems but only one theory of perception
Authors: Darren Burke, William G. Hayward
Journal: Behavioral and Brain Sciences (2002)

The parallel drawn by Norman between the dorsal and ventral systems and direct and indirect approaches is based on two misrepresentations of the direct approach – that it is concerned only with the unconscious control of action, and that it cannot explain learning. We propose a way of understanding the visual system differences from within the direct approach.
Effect of Continuous Glucose Monitoring on Hypoglycemia in Type 1 Diabetes
Authors: Tadej Battelino, Moshe Phillip, Natasa Bratina, Revital Nimri, Per Oskarsson, Jan Bolinder
Journal: Diabetes Care (2011)

To assess the impact of continuous glucose monitoring on hypoglycemia in people with type 1 diabetes.In this randomized, controlled, multicenter study, 120 children and adults on intensive therapy for type 1 diabetes and a screening level of glycated hemoglobin A(1c) (HbA(1c)) <7.5% were randomly assigned to a control group performing conventional home monitoring with a blood glucose meter and wearing a masked continuous glucose monitor every second week for five days or to a group with real-time continuous glucose monitoring. The primary outcome was the time spent in hypoglycemia (interstitial glucose concentration <63 mg/dL) over a period of 26 weeks. Analysis was by intention to treat for all randomized patients.The time per day spent in hypoglycemia was significantly shorter in the continuous monitoring group than in the control group (mean ± SD 0.48 ± 0.57 and 0.97 ± 1.55 h/day, respectively; ratio of means 0.49; 95% CI 0.26-0.76; P = 0.03). HbA(1c) at 26 weeks was lower in the continuous monitoring group than in the control group (difference -0.27%; 95% CI -0.47 to -0.07; P = 0.008). Time spent in 70 to 180 mg/dL normoglycemia was significantly longer in the continuous glucose monitoring group compared with the control group (mean hours per day, 17.6 vs. 16.0, P = 0.009).Continuous glucose monitoring was associated with reduced time spent in hypoglycemia and a concomitant decrease in HbA(1c) in children and adults with type 1 diabetes.
Major histocompatibility complex class II+B7-1+ tumor cells are potent vaccines for stimulating tumor rejection in tumor-bearing mice.
Authors: S Baskar, L Glimcher, N Nabavi, R T Jones, S Ostrand-Rosenberg
Journal: The Journal of Experimental Medicine (1995)

Mice carrying large established major histocompatibility complex (MHC) class 1+ sarcoma tumors can be successfully treated by immunization with genetically engineered sarcoma cells transfected with syngeneic MHC class II plus B7-1 genes. This approach is significantly more effective than previously described strategies using cytokine- or B7-transduced tumor cells which are only effective against smaller tumor loads, and which cannot mediate regression of longer-term established tumors. The most efficient tumor rejection occurs if both the class II and B7-1 molecules are coexpressed on the same tumor cell. Immunity induced by immunization with class II+B7-1(+)-transfected sarcoma cells involves CD4+ and CD8+ T cells, suggesting that the increased effectiveness of the transfectants is due to their ability to activate both of these T cell populations.
Gentamicin-Induced Correction of CFTR Function in Patients with Cystic Fibrosis and<i>CFTR</i>Stop Mutations
Authors: Michael Wilschanski, Yaacov Yahav, Yasmin Yaacov, Hannah Blau, Lea Bentur, Joseph Rivlin, Micha Aviram, Tali Bdolah-Abram, Zsuzsa Bebok, Liat Shushi, Batsheva Kerem, Eitan Kerem
Journal: New England Journal of Medicine (2003)

Mutations in the cystic fibrosis transmembrane conductance regulator (CFTR) gene containing a premature termination signal cause a deficiency or absence of functional chloride-channel activity. Aminoglycoside antibiotics can suppress premature termination codons, thus permitting translation to continue to the normal end of the transcript. We assessed whether topical administration of gentamicin to the nasal epithelium of patients with cystic fibrosis could result in the expression of functional CFTR channels.