tbuckley/cabot-search huggingface dataset:
Clinical utility of a circulating tumor cell assay in Merkel cell carcinoma
Authors: Astrid Blom, Shailender Bhatia, Stephanie Pietromonaco, Karen Koehler, Jayasri G. Iyer, Kotaro Nagase, Kelly Paulson, Daniel E. Sabath, Paul Nghiem
Journal: Journal of the American Academy of Dermatology (2014)
Conversations with Lasker giants
Authors: Ushma S. Neill
Journal: Journal of Clinical Investigation (2014)

For the last five years, the JCI has had the privilege of working with the Albert and Mary Lasker Foundation to write profiles on the prizewinners. Coverage of the 2014 laureates will be featured in the October issue. In addition to the news features on the prizes, I’ve had the pleasure of interviewing several of the previous years’ laureates (Figure ​(Figure1)1) for the series “Conversations with Giants in Medicine.”



Figure 1

Lasker laureates interviewed in the series Conversations with Giants in Medicine. 



The interviews provide rich insights into scientific breakthroughs and inspiring glimpses of the researchers themselves. I can appreciate, however, that not everyone has the 30–45 minutes of free time necessary to watch an entire interview, so I’ve spliced together some of the laureates’ finer moments into a highlight reel, narrated together with Claire Pomeroy, the President of the Albert and Mary Lasker Foundation.

Many of the laureates faced scientific and life challenges and triumphed over them with perseverance, resilience, support of colleagues and loved ones, and often a marvelous sense of humor. We can all be inspired by their stories. The video can be found at http://www.jci.org/videos/cgm and will also be featured on the Lasker web site.

After watching the clips, I hope you are able to identify a bit more with these remarkable scientists. Many of them have humble beginnings and had no idea they’d end up as scientists and doctors. And many of them dream of what else they could have become — tennis players, teachers, and bartenders. Some had similar struggles, and all have experienced the joy of discovery. The true common thread among them is that they’ve all had extraordinary lives in science, as marked by being recipients of one of the most prestigious prizes in science, the Lasker Award.
Loteprednol Etabonate Ophthalmic Suspension, 0.2% Is As Safe as Olopatadine Hydrochloride Ophthalmic Solution, 0.1% With Superior Relief of Signs and Symptoms In The Treatment of Seasonal Allergic Conjunctivitis
Authors: A. Elion-Mboussa, L. Gong, L. Roy, B. Zhu, H. DeCory, E. Chu
Journal: Journal of Allergy and Clinical Immunology (2012)
Everolimus in Advanced Pancreatic Neuroendocrine Tumors: The Clinical Experience
Authors: James C. Yao, Alexandria T. Phan, Valentine Jehl, Gaurav Shah, Funda Meric-Bernstam
Journal: Cancer Research (2013)

Abstract The incidence of neuroendocrine tumors (NET) has increased dramatically in the past 30 years. This information has revitalized basic and clinical research into the molecular biology of NET and has resulted in the recent approval of new therapies for pancreatic NET (pNET), including the oral inhibitor of the mTOR everolimus. Everolimus significantly improved progression-free survival among patients with pNET in the phase III RADIANT-3 study. Here, we review the clinical studies showing the efficacy of everolimus in pNET and summarize the translational science from these studies. To understand the mechanisms of resistance and cause of treatment failure, we compared the type of progression events observed in the everolimus and placebo arms of the RADIANT-3 study. Comparison of the everolimus arm to the placebo arm indicated the fractions of progression events due to new metastasis only (21% vs. 22%), growth of preexisting lesions only (54% vs. 49%), and new metastasis along with growth of preexisting lesions (24% vs. 27%) were similar. These results suggest that although everolimus delays disease progression in patients with pNET, patients who experience disease progression while on everolimus do not appear to have a more aggressive metastatic phenotype than those whose disease progresses while on placebo. Cancer Res; 73(5); 1449–53. ©2013 AACR.
Abstract LB-86: Dependent and independent tumor suppression function of ARF and p53 in murine BCC carcinogenesis in Ptch1+/- mice
Authors: Grace Y. Wang, Carla Wood, Hiroe Hu, John Dolorito, Eileen Libove, Ervin H. Eptein
Journal: Cancer Research (2014)

Abstract Basal cell carcinoma (BCC), the most commonly diagnosed human cancer, is driven by aberrant activation of hedgehog (HH) signaling. In addition, we have found that p53 is a potent inhibitor of HH-driven BCC carcinogenesis - ablation of p53 in Ptch1+/- K14CreER2 p53fl/fl (PF mice) dramatically accelerates BCC formation with a shorter tumor latency and a 10 fold increase of tumor burden. To begin to determine how p53 is activated in this Ptch1+/- murine BCC model, we investigated the role of p19ARF in translating oncogene-induced stress (OIS) into p53 activation. We bred Ptch1+/- mice with ARFGFP/GFP to generate Ptch1+/- ARFGFP/GFP (ARF mice), lacking functional ARF. In addition, we crossed ARF mice and PF mice to generate ARF/p53 double deletion mice (DD mice), treated ARF, PF and DD mice as well as Ptch1+/- (ARF+/+, p53+/+) with IR at mouse age 8w, and quantified BCC formation. .As assessed in age 5m skin biopsies, PF and DD mice had a significantly higher microscopic BCC tumor burden than did ARF and Ptch1+/- mice. There was no significant difference between PF and DD or between ARF and Ptch1+/-. ARF and PF mice developed visible BCC starting at 5-6 m. By contrast, DD mice had visible BCCs as early as age 4m, a statistically different age of onset. Consistent with our previous findings, Ptch1+/- mice did not form any visible BCCs until age 9 m or later. These data indicate that loss of functional ARF or of p53 promotes malignant conversion of microscopic BCCs to visible BCCs. However, only loss of p53, but not loss of ARF, enhances tumor initiation. To gain further insights in the molecular mechanisms differentiating these tumors, we examined the whole genome expression analysis by RNA-seq. Taken together, our findings suggest that both ARF-dependent and -independent activation of p53 is involved in BCC carcinogenesis. ARF-mediated p53 activation, presumably via the OIS pathway, appears to be crucial in regulating malignant transformation of BCC, while ARF-independent p53 activation inhibits tumor initiation. Citation Format: Grace Y. Wang, Carla Wood, Hiroe Hu, John Dolorito, Eileen Libove, Ervin H. Eptein. Dependent and independent tumor suppression function of ARF and p53 in murine BCC carcinogenesis in Ptch1+/- mice. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr LB-86. doi:10.1158/1538-7445.AM2014-LB-86
Screening and confirmatory testing of cadaver organ donors for hepatitis C virus infection: A U.S. National Collaborative Study
Authors: Brian J.G. Pereira, Teresa L. Wright, Christopher H. Schmid, Christopher F. Bryan, Ramsey C. Cheung, E. Shannon Cooper, Henry Hsu, Randall Heyn-Lamb, Jimmy A. Light, Douglas J. Norman, David H. Van Thiel, Barbara G. Werner, Charles E. Wright, Andrew S. Levey
Journal: Kidney International (1994)
Trichophyton Rubrum Infection in Families
Authors: M. P. English
Journal: BMJ (1957)

ACUTE AMPHETAMINE POISONING BRxTIsw)~~~~~E ICQ JOURKU the contents of one and a half benzedrine inhalers, an unorthodox but readily available source of the drug.One case developed an acute psychosis, a common feature of severe amphetamine intoxication which requires heavy barbiturate sedation both for prophy- laxis and for treatment.We thank Dr. Clifford Hoyle for his guidance and for permis- sion to publish these cases.We are also indebted to-Dr.P. H. Connell (Maudsley Hospital) for estimating the amphetamine ex- cretion in two of the cases and for much valuable advice.
Abstract IA15: VEGF-targeted therapies: Biomarkers, biology, and understanding resistance
Authors: Lee M. Ellis
Journal: Clinical Cancer Research (2012)

Abstract Despite major advances in the clinical development of VEGF-targeted therapy, most patients' tumors are considered to be inherently resistant. When response is obtained, the benefit of VEGF inhibitors is transient, lasting weeks to months, in contrast to the original hypothesis that cancer would be converted to a chronic disease with this therapeutic approach. The mechanisms of action of this class of drugs vary among tumor types and therefore resistance mechanisms and biomarkers are likely to be tumor-type specific. Clinical studies have begun to uncover potential biomarkers that require validation in prospective studies. For example, data reported at the 2011 ESMO meeting suggested that circulating VEGF, as detected by a new ELISA, may be able to determine the population of patients likely to benefit from the use of bevacizumab, in some, but not all studies. In addition, several clinical studies reported this past year have shown that continued VEGF-inhibition through multiple lines of therapy may be of benefit to patients. These clinical studies suggest that resistance may be a relative term: although patients eventually progress, continued VEGF inhibition beyond initial progression may be of clinical benefit in selected patients. There is much work to be done in the field of biomarkers for VEGF-targeted therapies, but these recent clinical studies provide insights that will hopefully provide the foundation for significant improvements in patient outcomes.
Clinical Methods of Neuro-Ophthalmologic Examinations
Authors: J. Lawton Smith
Journal: JAMA (1962)

The second edition of this text has long been awaited since the 1946 edition has been out of print for many years. The book has the most complete discussion of optokinetic nystagmus available in any text. Topical diagnosis of 3 nerve palsies is presented in the most thorough fashion of any available text. The differential diagnosis of anisocoria is handled quite well. Excellent sections on the chiasm, nystagmus, sylvian aqueduct syndrome, and gaze movements are included, besides being a good source of eponyms. The main criticism of the second edition is the omissions. Many subjects of current neuro-ophthalmologic interest are not included. However, although restricted in size, there are new sections on electromyography, electroretinography, and pupillography. In summary, although not a complete reference source of neuro-ophthalmology, this is a valuable textbook.
PROX1 promotes hepatocellular carcinoma metastasis by way of up-regulating hypoxia-inducible factor 1α expression and protein stability
Authors: Yanfeng Liu, Ju-Bo Zhang, Yi Qin, Wei Wang, Lili Wei, Yigang Teng, Lei Guo, Bo Zhang, Zhenhai Lin, Jing Liu, Zheng-Gang Ren, Qing-Hai Ye, Youhua Xie
Journal: Hepatology (2013)

Hepatocellular carcinoma (HCC) is one of the most common cancers and the third leading cause of death from cancer worldwide. HCC has a very poor prognosis because of tumor invasiveness, frequent intrahepatic spread, and extrahepatic metastasis. The molecular mechanism of HCC invasiveness and metastasis is poorly understood. The homeobox protein PROX1 is required for hepatocyte migration during mouse embryonic liver development. In this study, we show that high PROX1 protein expression in primary HCC tissues is associated with significantly worse survival and early tumor recurrence in postoperative HCC patients. Knockdown of PROX1 expression in HCC cells inhibited cell migration and invasiveness in vitro and HCC metastasis in nude mice while overexpression of PROX1 in HCC cells promoted these processes. PROX1's pro -metastasis activity is most likely attributed to its up-regulation of hypoxia-inducible factor 1α ( HIF-1α ) transcription and stabilization of HIF-1α protein by recruiting histone deacetylase 1 (HDAC1) to prevent the acetylation of HIF-1α, which subsequently induces an epithelial-mesenchymal transition response in HCC cells. We further demonstrated the prognostic value of using the combination of PROX1 and HDAC1 levels to predict postoperative survival and early recurrence of HCC. Conclusion : PROX1 is a critical factor that promotes HCC metastasis. (Hepatology 2013;58:692-705)
Aspirin use after diagnosis but not prediagnosis improves established colorectal cancer survival: a meta-analysis
Authors: Peiwei Li, Han Wu, Honghe Zhang, Yu Shi, Jinming Xu, Yao Ye, Dajing Xia, Jun Yang, Jianting Cai, Yihua Wu
Journal: Gut (2014)

The objective of this meta-analysis was to systematically assess the survival benefit of aspirin use before or after diagnosis for patients with colorectal cancer (CRC).Relevant studies were identified through searching PubMed, Embase and Cochrane databases before May 2014. Two investigators extracted data independently for baseline characteristics and outcomes from the included studies. Either a fixed-effects or a random-effects model was derived to composite the pooled HR for overall mortality and CRC-specific mortality of CRC.Seven studies on postdiagnosis aspirin therapy and seven studies on prediagnosis aspirin use were finally included in this meta-analysis. The overall survival benefit associated with postdiagnosis aspirin use represented an HR of 0.84 (95% CI 0.75 to 0.94). This effect was observed both in colon cancer (HR=0.78, 95% CI 0.64 to 0.96) and in rectal cancer (HR=0.90, 95% CI 0.83 to 0.98). Besides, the survival benefit of postdiagnosis aspirin use appeared to be confined to those patients with positive prostaglandin endoperoxide synthase 2 (PTGS2, also known as cyclooxygenase-2, COX-2) expression (HR=0.65, 95% CI 0.50 to 0.85) and with mutated PIK3CA tumours (HR=0.58, 95% CI 0.37 to 0.90). Aspirin use postdiagnosis was not associated with CRC-specific mortality (HR=0.77, 95% CI 0.52 to 1.14). We observed no evidence of an association between prediagnosis aspirin use and CRC overall mortality (HR=1.01, 95% CI 0.96 to 1.06) or CRC-specific mortality (HR=0.93, 95% CI 0.82 to 1.05).These findings provide further indication that postdiagnosis aspirin therapy improved CRC overall survival, especially for patients with positive PTGS2 (COX-2) expression and mutated PIK3CA tumours.
Cardiac Status in Juvenile Borderline Hypertension
Authors: WALTER S. CULPEPPER
Journal: Annals of Internal Medicine (1983)

A prospective M-mode echocardiographic study was done to look for early cardiovascular changes in children prone to hypertension with blood pressures between the 75th and 95th percentiles for age. Average systolic/diastolic pressures in 27 children with borderline hypertension were 137/89 mm Hg compared to 110/68 mm Hg for the 26 controls. Echocardiographic measurements were normalized for comparison using two methods. The borderline hypertensive group mean values were significantly greater than controls for left ventricular wall thickness (p < 0.05 for method 1; p < 0.001 for method 2), left ventricular mass (p < 0.001; p < 0.005) and left ventricular wall thickness to radius ratio (p < 0.001, both methods). Echocardiographic estimates of left ventricular function were lower in the hypertensive group. This study suggests that cardiac hypertrophy can be shown by noninvasive means in some children before arterial pressure becomes elevated. To assess the incidence and possible consequences of early target organ changes, more extensive clinical evaluation of borderline hypertension in children is recommended.
N-acetylcysteine potentiates platelet inhibition by endothelium-derived relaxing factor.
Authors: J Stamler, M E Mendelsohn, P Amarante, D Smick, N Andon, P F Davies, J P Cooke, J Loscalzo
Journal: Circulation Research (1989)

Recent evidence suggests that endothelium-derived relaxing factor exhibits properties of nitric oxide. Like nitric oxide, it inhibits platelet function and mediates its effects by elevating intracellular cyclic GMP. In this study we have investigated the role of reduced thiol in the mechanism of action of endothelium-derived relaxing factor on platelets. Bovine aortic endothelial cells were grown on microcarrier beads and pretreated with aspirin before use. Endothelial cells stimulated with bradykinin or exposed to stirred medium expressed a dose-dependent inhibition of platelet aggregation that was potentiated by the reduced thiol, N-acetylcysteine. Endothelial cell-mediated platelet inhibition was attenuated by methylene blue. Inhibition of platelet aggregation by endothelial cells was associated with a rise in platelet intracellular cyclic GMP, an effect that was enhanced by N-acetylcysteine. These data show that 1) the reduced thiol N-acetylcysteine potentiates platelet inhibition by endothelium-derived relaxing factor and 2) this effect is associated with increasing intracellular platelet cyclic GMP levels.
Abstract 5449: Down-regulation of miR-200b and induction of ZEB1 and ZEB2 promote arsenic-transformed cell migration and invasion
Authors: Zhishan Wang, Theresa Fisher, Chengfeng Yang
Journal: Cancer Research (2012)

Abstract Arsenic is one of the most common environmental contaminants and a well-recognized human carcinogen. Long-term exposure to arsenic causes human bronchial epithelial cell (HBEC) malignant transformation and lung cancer. However, the mechanism of arsenic lung carcinogenesis is not clear; and the migratory and invasive properties of arsenic-transformed cells have been rarely studied. We found that arsenic-transformed HBECs (As-HBECs) were highly migratory and invasive. MicroRNA-200b (miR-200b) expression was down-regulated and epithelial-to-mesenchymal transition-inducing transcription factors ZEB1 (zinc-finger E-box-binding homeobox factor 1) and ZEB2 were up-regulated in As-HBECs. Akt and extracellular signal-regulated protein kinase 1/2 (Erk1/2) were strongly activated in As-HBECs. Stably expressing miR-200b in As-HBECs abolished Akt and Erk1/2 activation, and completely suppressed cell migration and invasion. Pharmacological inactivation of Akt but not Erk1/2 significantly decreased cell migration and invasion. Inhibition of Akt reduced the expression of ZEB1 and ZEB2 and impaired As-HBEC migration and invasion. Our findings indicate that Akt activation plays a critical role in enabling arsenic-transformed HBEC migration and invasion through promoting ZEB1 and ZEB2 expression. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 5449. doi:1538-7445.AM2012-5449
Comparison of peripheral blood lymphocyte subtypes in renal transplant patients with or without hepatitis C infection
Authors: Meltem Sezis, Galip Ersoz, Huseyin Toz, Zeki Karasu, Ali Kokuludag, Ercan Ok, Arzu Celebi, Ulus Akarca, Ender Terzioglu
Journal: Journal of Hepatology (2002)
A perceptual theory of knowledge: Specifying some details
Authors: Aaro Toomela
Journal: Behavioral and Brain Sciences (1999)

We attempt to resolve some details of Barsalou's theory. (1) The mechanism that guides selection of perceptual information may be the efferent control of activity. (2) Information about a world that is not accessible to the senses can be constructed in the process of semiotic mediation. (3) Introspection may not be a kind of perception; rather, semiotically mediated information processing might be necessary for the emergence of introspection.
Reduction of infarct size by gentle reperfusion without activation of reperfusion injury salvage kinases in pigs
Authors: J. Musiolik, P. van Caster, A. Skyschally, K. Boengler, P. Gres, R. Schulz, G. Heusch
Journal: Cardiovascular Research (2009)

Reperfusion is mandatory to salvage ischaemic myocardium from infarction, but also induces additional reperfusion injury and contributes to infarct size (IS). Gentle reperfusion (GR) has been proposed to attenuate reperfusion injury, but this remains contentious. We now investigated whether (i) GR reduces IS and (ii) GR is associated with the activation of reperfusion injury salvage kinases (RISK). Anaesthetized pigs were subjected to 90 min left anterior descending coronary artery hypoperfusion and 120 min reperfusion. GR was induced by slowly increasing coronary inflow back to baseline over 30 min, using an exponential algorithm [F(t) = Fi+e−(0.1t(min)−3)·(Fb−Fi); Fb, coronary inflow at baseline; Fi, coronary inflow during ischaemia; n = 12]. Pigs subjected to immediate full reperfusion (IFR; n = 13) served as controls. IS was determined by triphenyl tetrazolium chloride staining. The expression level of phosphorylated RISK proteins was determined by western blot analysis in myocardial biopsies taken at baseline, after 80–85 min ischaemia and at 10, 30, and 120 min reperfusion. In additional experiments with IFR (n = 3) and GR (n = 3), the PI3–AKT and MEK1/2–ERK1/2 pathways were pharmacologically blocked (BL). IS was 37 ± 2% (mean ± SEM) of the area at risk with IFR and 29 ± 1% (P < 0.05) with GR. RISK phosphorylation was similar between GR and IFR at baseline and 85 min ischaemia. At 10 min reperfusion, RISK phosphorylation was increased with IFR, but not with GR. At 30 and 120 min reperfusion, RISK phosphorylation was still greater with IFR than GR. RISK blockade did not abolish the IS reduction by GR (BL-IFR: 27 ± 4% of the area at risk; BL-GR: 42 ± 5%; P < 0.05). Gentle reperfusion reduces infarct size in pigs, but RISK activation is not causally involved in this infarct size reduction.
Packages of Care for Attention-Deficit Hyperactivity Disorder in Low- and Middle-Income Countries
Authors: Alan J. Flisher, Katherine Sorsdahl, Sean Hatherill, Sonia Chehil
Journal: PLoS Medicine (2010)

This is the last in a series of articles highlighting the delivery of ''packages of care'' for mental health disorders in low-and middleincome countries.Packages of care are combinations of treatments aimed at improving the recognition and management of conditions to achieve optimal outcomes.
A COMPLICATED CASE OF APPENDICITIS
Authors: E. S. Stevenson
Journal: BMJ (1906)

O*,-all the surgical diseases there are few, if any, which present the same constant similarity of symptoms, which result,in so many different pathological changes, and lead toisuch a variety of complications as acute appendicitis.The following is an illustration: Miss Z., a school teacher, aged 23, had been for several months failing in health, losing flesb, anaemic, suffering from
IGFBP-3, a sensitive marker of physical training and overtraining
Authors: M Elloumi, N El Elj, M Zaouali, F Maso, E Filaire, Z Tabka, G Lac
Journal: British Journal of Sports Medicine (2005)

To investigate the response of the somatotrope axis (insulin-like growth factor-1 (IGF-1), insulin-like growth factor binding protein-3 (IGFBP-3)) to intense exercise in relation to tiredness. The study involved 11 rugby players who completed a questionnaire intended to evaluate fitness or, conversely, overtraining and who agreed to plasma samples being taken before and after an international rugby match. The main finding of our study is that we observed strong negative correlations between IGF-1 (r = 0.652) and IGFBP-3 (r = 0.824) levels and the overtraining state estimated using the French Society of Sport Medicine questionnaire. In particular, there was a fall (of up to 25%) in IGFBP-3 levels after the match in the more fatigued subjects compared to an increase (of up to 40%) in fit subjects. A fall in IGFBP-3 in response to an intense bout of exercise may represent an index of tiredness in highly trained sportsmen, as indicated by the scores obtained from the overtraining questionnaire.
Cancer Stem Cells and Vascular NICHE
Authors: N. Takakura, T. Shimizu, H. Saya, N. Haraguchi, D. Sakai, T. Satoh, H. Yamamoto, H. Nagano, H. Ishii, Y. Doki, M. Mori, F. Ishikawa, K. Akashi
Journal: Annals of Oncology (2012)