tbuckley/cabot-search huggingface dataset:
A zebrafish model of tauopathy allows in vivo imaging of neuronal cell death and drug evaluation
Authors: Dominik Paquet, Ratan Bhat, Astrid Sydow, Eva-Maria Mandelkow, Stefan Berg, Sven Hellberg, Johanna Fälting, Martin Distel, Reinhard W. Köster, Bettina Schmid, Christian Haass
Journal: Journal of Clinical Investigation (2009)

Our aging society is confronted with a dramatic increase of patients suffering from tauopathies, which include Alzheimer disease and certain frontotemporal dementias. These disorders are characterized by typical neuropathological lesions including hyperphosphorylation and subsequent aggregation of TAU protein and neuronal cell death. Currently, no mechanism-based cures are available. We generated fluorescently labeled TAU transgenic zebrafish, which rapidly recapitulated key pathological features of tauopathies, including phosphorylation and conformational changes of human TAU protein, tangle formation, neuronal and behavioral disturbances, and cell death. Due to their optical transparency and small size, zebrafish larvae are well suited for both in vivo imaging and drug development. TAU-induced neuronal cell death was imaged by time-lapse microscopy in vivo. Furthermore, we used this zebrafish model to identify compounds targeting the TAU kinase glycogen synthase kinase 3beta (GSK3beta). We identified a newly developed highly active GSK3beta inhibitor, AR-534, by rational drug design. AR-534 reduced TAU phosphorylation in TAU transgenic zebrafish. This transgenic zebrafish model may become a valuable tool for further studies of the neuropathology of dementia.
Picropodophyllotoxin or Podophyllotoxin Does Not Induce Cell Death via Insulin-like Growth Factor-I Receptor
Authors: Stig Linder, Maria C. Shoshan, Radhey S. Gupta
Journal: Cancer Research (2007)

To the Editor: 

The cyclolignan picropodophyllotoxin (PPP) was recently launched as an anticancer drug specifically targeting insulin-like growth factor-I receptor (IGF-IR; ref. [1][1]). PPP is an epimer of podophyllotoxin (PPT), an established inhibitor of microtubule assembly used to treat
Association Between Hospitalization With Community-Acquired Laboratory-Confirmed Influenza Pneumonia and Prior Receipt of Influenza Vaccination
Authors: Carlos G. Grijalva, Yuwei Zhu, Derek J. Williams, Wesley H. Self, Krow Ampofo, Andrew T. Pavia, Chris R. Stockmann, Jonathan McCullers, Sandra R. Arnold, Richard G. Wunderink, Evan J. Anderson, Stephen Lindstrom, Alicia M. Fry, Ivo M. Foppa, Lyn Finelli, Anna M. Bramley, Seema Jain, Marie R. Griffin, Kathryn M. Edwards
Journal: JAMA (2015)

<h3>Importance</h3> Few studies have evaluated the relationship between influenza vaccination and pneumonia, a serious complication of influenza infection. <h3>Objective</h3> To assess the association between influenza vaccination status and hospitalization for community-acquired laboratory-confirmed influenza pneumonia. <h3>Design, Setting, and Participants</h3> The Etiology of Pneumonia in the Community (EPIC) study was a prospective observational multicenter study of hospitalizations for community-acquired pneumonia conducted from January 2010 through June 2012 at 4 US sites. In this case-control study, we used EPIC data from patients 6 months or older with laboratory-confirmed influenza infection and verified vaccination status during the influenza seasons and excluded patients with recent hospitalization, from chronic care residential facilities, and with severe immunosuppression. Logistic regression was used to calculate odds ratios, comparing the odds of vaccination between influenza-positive (case) and influenza-negative (control) patients with pneumonia, controlling for demographics, comorbidities, season, study site, and timing of disease onset. Vaccine effectiveness was estimated as (1 − adjusted odds ratio) × 100%. <h3>Exposure</h3> Influenza vaccination, verified through record review. <h3>Main Outcomes and Measures</h3> Influenza pneumonia, confirmed by real-time reverse-transcription polymerase chain reaction performed on nasal/oropharyngeal swabs. <h3>Results</h3> Overall, 2767 patients hospitalized for pneumonia were eligible for the study; 162 (5.9%) had laboratory-confirmed influenza. Twenty-eight of 162 cases (17%) with influenza-associated pneumonia and 766 of 2605 controls (29%) with influenza-negative pneumonia had been vaccinated. The adjusted odds ratio of prior influenza vaccination between cases and controls was 0.43 (95% CI, 0.28-0.68; estimated vaccine effectiveness, 56.7%; 95% CI, 31.9%-72.5%). <h3>Conclusions and Relevance</h3> Among children and adults hospitalized with community-acquired pneumonia, those with laboratory-confirmed influenza-associated pneumonia, compared with those with pneumonia not associated with influenza, had lower odds of having received influenza vaccination.
Human Vascular Smooth Muscle Cells but Not Endothelial Cells Express Prostaglandin E Synthase
Authors: Marta Soler, Mercedes Camacho, José-Román Escudero, Miguel A. Iñiguez, Luís Vila
Journal: Circulation Research (2000)

Abstract —In a previous work, we postulated that endothelial cells possess only the following 2 enzymes involved in prostanoid synthesis: cyclooxygenase and prostacyclin synthase. The present work focused on investigating the expression of prostaglandin (PG) E synthase (PGES) in vascular cells. After incubation of vascular smooth muscle cells (SMCs) and human umbilical vein endothelial cells (HUVECs) with [ 14 C]arachidonic acid, the profile of prostanoid synthesis was assessed by HPLC. Untransformed PGH 2 released by the cells was evaluated as the difference in the formation of PGF 2α in the incubations performed in the presence and in the absence of SnCl 2 . Resting SMCs and SMCs stimulated with phorbol 12-myristate 13-acetate (PMA), lipopolysaccharide (LPS), interleukin (IL)-1β, and tumor necrosis factor (TNF)-α formed PGE 2 and PGI 2 (evaluated as 6-oxo-PGF 1α ), and in the presence of SnCl 2 only a small amount of PGE 2 was deviated toward PGF 2α . In contrast, resting and stimulated HUVECs produced PGI 2 , PGE 2 , PGF 2α , and PGD 2 , and SnCl 2 completely diverted PGE 2 and PGD 2 toward PGF 2α . Reverse transcriptase–polymerase chain reaction analysis shows that mRNA encoding for PGES was not present in HUVECs and in endothelial cells from saphenous vein. Nevertheless, PGES was expressed in SMCs and induced by IL-1β and TNF-α, and by PMA and LPS, although to a lesser extent. Whereas SMC stimulation led to an increase in the synthesis of PGE 2 and PGI 2 but not of untransformed PGH 2 , stimulation of endothelial cells resulted in an enhanced release of the vasoconstricting prostanoid PGH 2 .
Impaired Tubular Uptake Explains Albuminuria in Early Diabetic Nephropathy
Authors: Leileata M. Russo, Ruben M. Sandoval, Silvia B. Campos, Bruce A. Molitoris, Wayne D. Comper, Dennis Brown
Journal: Journal of the American Society of Nephrology (2009)

Understanding the pathogenesis of albuminuria in diabetic nephropathy is important to improve methods for early diagnosis and treatment. In this study, we addressed whether albuminuria in diabetes results from altered glomerular filtration and/or altered processing of filtered albumin by the proximal tubule. Type 1 diabetic Munich Wistar rats developed albuminuria after 12 wk of diabetes. Intravital two-photon microscopy revealed similar glomerular permeability in the diabetic and control animals, assessed using both albumin-Alexa568 and 69-kD FITC-dextran; however, diabetic animals demonstrated significantly less filtered fluorescent albumin in renal proximal tubule (PT) cells compared with control animals. We also observed increased albumin-derived urinary peptide excretion in diabetic animals, and hyperglycemia modulated this peptideuria. In conclusion, in the early stages of diabetic nephropathy, the PT plays a major role in the development of albuminuria, which may be preceded by peptideuria.
Role of Surgery in the Treatment of Patients With Stage 4 Neuroblastoma Age 18 Months or Older at Diagnosis
Authors: Thorsten Simon, Beate Häberle, Barbara Hero, Dietrich von Schweinitz, Frank Berthold
Journal: Journal of Clinical Oncology (2013)

Purpose Although intensive multimodal treatment has improved the prognosis of patients with metastatic neuroblastoma, the impact of primary tumor resection on outcome is a matter of medical debate. Patients and Methods Patients from the German prospective clinical trial NB97 with stage 4 neuroblastoma and age 18 months or older at diagnosis were included. Operation notes and imaging reports were reviewed by two independent experienced physicians. Finally, the extent of tumor resections was correlated with local control rate and outcome. Results A total of 278 patients were included in this study. Image-defined risk factors present at diagnosis were found to be predictive for the extent of tumor resection at first (P &lt; .001) and best (P &lt; .001) operation. No patient died from surgery. Before chemotherapy, complete resection, incomplete resection, and biopsy or no surgery were performed in 6.1%, 5.0%, and 88.5% of patients, respectively. The extent of first operation had no impact on event-free survival (EFS; P = .207), local progression–free survival (LPFS; P = .195), and overall survival (OS; P = .351). After induction chemotherapy, 54.7% of patients underwent complete resection of the primary tumor, 30.6% underwent incomplete resection, and 13.3% had only biopsy or no surgery of the primary tumor. The extent of best operation also had no impact on EFS (P = .877), LPFS (P = .299), and OS (P = .778). Moreover, multivariate analyses showed that surgery did not affect EFS, LPFS, and OS. Conclusion In intensively treated patients with stage 4 neuroblastoma age 18 months or older at diagnosis, surgery of the primary tumor site has no impact on local control rate and outcome.
Estrogen Protects Lenses against Cataract Induced by Transforming Growth Factor-β (TGFβ)
Authors: Angela M. Hales, Coral G. Chamberlain, Christopher R. Murphy, John W. McAvoy
Journal: The Journal of Experimental Medicine (1997)

Cataract, already a major cause of visual impairment and blindness, is likely to become an increasing problem as the world population ages. In a previous study, we showed that transforming growth factor-β (TGFβ) induces rat lenses in culture to develop opacities and other changes that have many features of human subcapsular cataracts. Here we show that estrogen protects against cataract. Lenses from female rats are more resistant to TGFβ-induced cataract than those from males. Furthermore, lenses from ovariectomized females show increased sensitivity to the damaging effects of TGFβ and estrogen replacement in vivo, or exposure to estrogen in vitro, restores resistance. Sex-dependent and estrogen-related differences in susceptibility to cataract formation, consistent with a protective role for estrogen, have been noted in some epidemiological studies. The present study in the rat indicates that estrogen provides protection against cataract by countering the damaging effects of TGFβ. It also adds to an increasing body of evidence that hormone replacement therapy protects postmenopausal women against various diseases.
Assessment of Flow Events at the Ductus VenosusInferior Vena Cava Junction and at the Foramen Ovale in Fetal Sheep by Use of Multimodal Ultrasound
Authors: Klaus G. Schmidt, Norman H. Silverman, Abraham M. Rudolph
Journal: Circulation (1996)

Background Previous techniques for the study of the fetal circulation did not permit assessment of phasic events associated with the cardiac cycle. We used multimodal ultrasound techniques to examine flow events that occur in the major veins and across the foramen ovale in the circulation of the fetal lamb. Methods and Results We studied eight fetal lambs instrumented with catheters in the superior and inferior venae cavae and a peripheral umbilical vein and performed ultrasound studies that included M-mode and two-dimensional imaging, pulsed and Doppler color flow ultrasound, and contrast echocardiography to evaluate flow in the ductus venosus, in both venae cavae, and through the foramen ovale. Two blood streams of different flow velocities were identified within the cephalic portion of the inferior vena cava. The stream that originated from the narrowed ductus venosus had a higher velocity than that from the caudal inferior vena cava (mean velocity, 57±13 versus 16±3 cm/s; P &lt;.0002). Facilitated by the eustachian valve and the septum primum, the ductus venosus stream preferentially passed through the foramen ovale to the left atrium. This flow occurred during most of the cardiac cycle, except for 19.6±2.3% of the cycle when the foramen ovale was closed during atrial contraction. Superior vena cava flow passed almost exclusively into the right atrium and tricuspid valve; a small amount that was refluxed from the right atrium into the inferior vena cava subsequently passed through the foramen into the left atrium. Conclusions Visualization of fetal circulatory streaming at the venous sites by ultrasound techniques aids in understanding the function of the fetal circulation and may be helpful in detecting the human fetus that is hemodynamically compromised.
Ghrelin treatment reverses the reduction in weight gain and body fat in gastrectomised mice
Authors: C Dornonville de la Cour, A Lindqvist, E Egecioglu, Y C L Tung, V Surve, C Ohlsson, J-O Jansson, C Erlanson-Albertsson, S L Dickson, R Håkanson
Journal: Gut (2005)

The gastric hormone ghrelin has been reported to stimulate food intake, increase weight gain, and cause obesity but its precise physiological role remains unclear. We investigated the long term effects of gastrectomy evoked ghrelin deficiency and of daily ghrelin injections on daily food intake, body weight, fat mass, lean body mass, and bone mass in mice.Ghrelin was given by subcutaneous injections (12 nmol/mouse once daily) for eight weeks to young female mice subjected to gastrectomy or sham operation one week previously.Gastrectomy reduced plasma concentrations of total ghrelin (octanoylated and des-octanoylated) and active (octanoylated) ghrelin by approximately 80%. Immediately after injection of ghrelin, the plasma concentration was supraphysiological and was still elevated 16 hours later. Daily food intake was not affected by either gastrectomy or ghrelin treatment. The effect of ghrelin on meal initiation was not studied. At the end point of the study, mean body weight was 15% lower in gastrectomised mice than in sham operated mice (p<0.001); daily ghrelin injections for eight weeks partially prevented this weight loss. In sham operated mice, ghrelin had no effect on body weight. The weight of fat was reduced in gastrectomised mice (-30%; p<0.01). This effect was reversed by ghrelin, enhancing the weight of fat in sham operated mice also (+20%; p<0.05). Gastrectomy reduced lean body mass (-10%; p<0.01) and bone mass (-20%; p<0.001) compared with sham operated mice. Ghrelin replacement prevented the gastrectomy induced decrease in lean body mass but did not affect bone. In sham operated mice, ghrelin affected neither of these two parameters.Ghrelin replacement partially reversed the gastrectomy induced reduction in body weight, lean body mass, and body fat but not in bone mass. In sham operated mice, ghrelin only increased fat mass. Our results suggest that ghrelin is mainly concerned with the control of fat metabolism and that ghrelin replacement therapy may alleviate the weight loss associated with gastrectomy.
ISOKINETIC MUSCLE PERFORMANCE IN MALE PROFESSIONAL HANDBALL PLAYERS
Authors: P Kaczmarek, P Lubiatowski, P Cisowski, W Dudzinski, M Grygorowicz, M Dzianach, L Romanowski
Journal: British Journal of Sports Medicine (2014)

Background Muscle strength and endurance of the shoulder rotators is important for overhead throwing performance and dynamic glenohumeral stability. Isokinetic assessment of shoulder internal and external rotators is commonly used by clinicians to assess muscle performance. Objective To evaluate the external (ER) and internal rotator (IR) muscles isokinetic peak torque, total work and strength ratios in handball players. Design Prospective study with control group and descriptive analysis. Setting Elite division handball players. Participants The pilot studies included 48 professional handball players of average age 24.0 (±4.5 years), height 187.1 (±5.9) and weight 9.0 (±11.6). Interventions Isokinetic tests were performed concentrically at 180 and 270 deg/s using Biodex System 3 PRO in standard sitting position. Main outcome measurements Isokinetic peak torque, total work and strength ratios. Results: The differences between the athletes and controls regarding the peak torque at 180 deg/s and total work at 270 deg/s of the ER and IR muscles for dominant and non dominant shoulder were statistically significant. The control group presented higher ratios (D 85.8±26.9; ND 82.8±23.4) than handball players (D 65.4±13.3; ND 63.0±16.0)–differences were statistically significant. There were statistical differences between dominant and non dominant shoulder in both group for total work of the ER muscles. There were no statistical differences between dominant and non dominant shoulder in both group for peak torque of the ER and IR muscles. Conclusions Handball players present higher isokinetic parameters comparing to normal population. The study establishes additional normative data on ER and IR muscle torque and total work on high-level male handball players.
Photodynamic therapy with BF-200 ALA for the treatment of actinic keratosis: results of a prospective, randomized, double-blind, placebo-controlled phase III study
Authors: R.-M. Szeimies, P. Radny, M. Sebastian, F. Borrosch, T. Dirschka, G. Krähn-Senftleben, K. Reich, G. Pabst, D. Voss, M. Foguet, R. Gahlmann, H. Lübbert, U. Reinhold
Journal: British Journal of Dermatology (2010)

Journal Article Photodynamic therapy with BF‐200 ALA for the treatment of actinic keratosis: results of a prospective, randomized, double‐blind, placebo‐controlled phase III study Get access R.‐M. Szeimies, R.‐M. Szeimies Department of Dermatology, Regensburg University Hospital, Regensburg, Germany Search for other works by this author on: Oxford Academic Google Scholar P. Radny, P. Radny Private Practice, Friedrichshafen, Germany Search for other works by this author on: Oxford Academic Google Scholar M. Sebastian, M. Sebastian Private Practice, Mahlow, Germany Search for other works by this author on: Oxford Academic Google Scholar F. Borrosch, F. Borrosch Private Practice, Vechta, Germany Search for other works by this author on: Oxford Academic Google Scholar T. Dirschka, T. Dirschka Private Practice, Wuppertal‐Barmen, Germany Search for other works by this author on: Oxford Academic Google Scholar G. Krähn‐Senftleben, G. Krähn‐Senftleben Private Practice, Blaubeuren, Germany Search for other works by this author on: Oxford Academic Google Scholar K. Reich, K. Reich Dermatologikum Hamburg, Hamburg, Germany Search for other works by this author on: Oxford Academic Google Scholar G. Pabst, G. Pabst FOCUS Clinical Drug Development GmbH, Neuss, Germany Search for other works by this author on: Oxford Academic Google Scholar D. Voss, D. Voss FOCUS Clinical Drug Development GmbH, Neuss, Germany Search for other works by this author on: Oxford Academic Google Scholar M. Foguet, M. Foguet Biofrontera Bioscience GmbH, Leverkusen, Germany Search for other works by this author on: Oxford Academic Google Scholar ... Show more R. Gahlmann, R. Gahlmann Biofrontera Bioscience GmbH, Leverkusen, Germany Reinhold Gahlmann. E‐mail: r.gahlmann@biofrontera.com Search for other works by this author on: Oxford Academic Google Scholar H. Lübbert, H. Lübbert Biofrontera Bioscience GmbH, Leverkusen, Germany Search for other works by this author on: Oxford Academic Google Scholar U. Reinhold U. Reinhold Medical Centre Bonn, Bonn, Germany Search for other works by this author on: Oxford Academic Google Scholar British Journal of Dermatology, Volume 163, Issue 2, 1 August 2010, Pages 386–394, https://doi.org/10.1111/j.1365-2133.2010.09873.x Published: 01 August 2010
Value of the Selvester 32-point QRS-score after acute myocardial infarctlon treated with primary percutaneous transluminal coronary angioplasty
Authors: J.H. De Sutter, C. Van de Wiele, Y. Taeymans, R. Dierckx, G. De Backer, D.L. Clement
Journal: Journal of the American College of Cardiology (1998)
A new health services platform for patient centred and personalised care
Authors: S. Ali, A. Schulte, R. Pope, D. Muir
Journal: BMJ (2014)

Social cues, such as eye gaze and pointing fingers, can increase the prioritisation of specific locations for cognitive processing.A previous study using a manual reaching task showed that, although both gaze and pointing cues altered target prioritisation (reaction times [RTs]), only pointing cues affected action execution (trajectory deviations).These differential effects of gaze and pointing cues on action execution could be because the gaze cue was conveyed through a disembodied head; hence, the model lacked the potential for a body part (i.e., hands) to interact with the target.In the present study, the image of a male gaze model, whose gaze direction coincided with two potential target locations, was centrally presented.The model either had his arms and hands extended underneath the potential target locations, indicating the potential to act on the targets (Experiment 1), or had his arms crossed in front of his chest, indicating the absence of potential to act (Experiment 2).Participants reached to a target that followed a nonpredictive gaze cue at one of three stimulus onset asynchronies.RTs and reach trajectories of the movements to cued and uncued targets were analysed.RTs showed a facilitation effect for both experiments, whereas trajectory analysis revealed facilitatory and inhibitory effects, but only in Experiment 1 when the model could potentially act on the targets.The results of this study suggested that when the gaze model had the potential to interact with the cued target location, the model's gaze affected not only target prioritisation but also movement execution.
ORAL CONTRACEPTIVES AND RHEUMATOID ARTHRITIS: FURTHER EVIDENCE FOR A PREVENTIVE EFFECT
Authors: J.P. Vandenbroucke, J.W. Boersma, J.J.M. Festen, H.A. Valkenburg, A. Cats, O. Huber-Bruning, J.J. Rasker
Journal: The Lancet (1982)
A Prospective Randomized Open Label Phase III Study of Geftinib Versus Docetaxel as Second or Third Line Therapy in Patients with Advanced Non Small Cell Lung Cancer in Asian Indians
Authors: A. Kapoor, N. Kumar, S. Narayan, R.K. Nirban, S. Maharia, S.K. Beniwal, S.L. Jakhar, H.S. Kumar
Journal: Annals of Oncology (2015)