tbuckley/cabot-search huggingface dataset:
Structure and Function of the HMGI(Y) Family of Architectural Transcription Factors
Authors: R Reeves
Journal: Environmental Health Perspectives (2000)

The three known members of the HMGI(Y) family of high-mobility group (HMG) mammalian nonhistone nuclear proteins (HMG-I, HMG-Y, and HMGI-C) are thought to participate in numerous biological processes (transcription, replication, retroviral integration, genetic recombination, etc.) by virtue of their ability to recognize and alter the structure of both DNA and chromatin substrates. In vitro and in vivo the HMGI(Y) proteins preferentially bind to the narrow minor groove of stretches of AT-rich DNA by means of highly conserved peptide motifs called AT hooks. In vitro the HMGI(Y) proteins also have the ability to selectively bind to distorted DNA structures and to bend, unwind, and supercoil DNA substrates. Additionally, the HMGI(Y) proteins have the ability to interact with various protein transcription factors both in vitro and in vivo. Specific protein-DNA and protein-protein interactions permit the HMGI(Y) proteins to function as architectural transcription factors that regulate gene expression in vivo by controlling the formation of stereospecific multiprotein complexes on the AT-rich regions of certain gene promoters. Transcriptional overexpression of the HMGI(Y) genes is highly correlated with both cancerous transformation and increased metastatic potential of a number of different cancers, and chromosomal rearrangements involving AT-hook motifs have been associated with various types of benign human mesenchymal tumors. The levels of HMGI(Y) proteins in human cells have been proposed to be sensitive diagnostic indicators of both neoplastic transformation and metastatic progression. Drugs based on the AT-hook motif offer the potential for development of new tumor therapeutic reagents.
IMPROVED LEFT VENTRICULAR FUNCTION IN ISCHEMIC HEART FAILURE PATIENTS AFTER PERCUTANEOUS LEFT VENTRICULAR PARTITIONING SYSTEM IMPLANTATION: AN ANALYSIS FROM THE PARACHUTE CHINA STUDY
Authors: Vivian G. Ng, Lissa Sugeng, Alexandra Lansky, Mary Jo Rizzo, Yong Huo, YueJin Yang, Runlin Gao
Journal: Journal of the American College of Cardiology (2016)
A Serologic Follow-up of the 1942 Epidemic of Post-Vaccination Hepatitis in the United States Army
Authors: Leonard B. Seeff, Gilbert W. Beebe, Jay H. Hoofnagle, James E. Norman, Zelma Buskell-Bales, Jeanne G. Waggoner, Neil Kaplowitz, Raymond S. Koff, John L. Petrini, Eugene R. Schiff, James Shorey, Malcolm M. Stanley
Journal: New England Journal of Medicine (1987)

An epidemic of icteric hepatitis in 1942 affected approximately 50,000 U.S. Army personnel. This outbreak was linked to specific lots of yellow-fever vaccine stabilized with human serum. To identify the responsible virus and the consequences of the epidemic, during 1985 we interviewed and serologically screened 597 veterans who had been in the army in 1942. These subjects were selected from three groups. Group I consisted of patients who had received the implicated vaccine and had jaundice; Group II had received the implicated vaccine but remained well; Group III had received a new, serum-free vaccine, with no subsequent jaundice. Ninety-seven percent of Group I, 76 percent of Group II, and 13 percent of Group III were positive for antibodies to hepatitis B virus. Only one subject had hepatitis B surface antigen, for a carrier rate of 0.26 percent among recipients of the implicated vaccine. The prevalence of hepatitis A antibody was similar in all three groups, and no subject had antibody to hepatitis delta virus. We conclude that hepatitis B caused the outbreak, that about 330,000 persons may have been infected, that the hepatitis B virus carrier state was a rare consequence, and that the outbreak induced hepatitis B antibodies that appear to persist for life.
Stricter rules and powers will help prevent another NHS scandal, says CQC chief
Authors: G. Iacobucci
Journal: BMJ (2013)

England’s healthcare regulator will be able to root out potential repeats of the Mid Staffordshire hospital scandal by enhancing its powers to scrutinise services, its chief executive has claimed.

David Behan, the chief executive of the Care Quality Commission, said that stricter requirements for registration coupled with increased surveillance through tougher inspections would allow the regulator to identify potential risks more quickly.1

In a speech at the Commissioning in Healthcare conference in London on 8 October, Behan acknowledged that there had been “a lot of controversy” about what the regulator’s role was and said that this had …
AB0736 Strategy for the Early Detection and Referral of Patients with Suspected Spondyloarthritis: Table 1
Authors: X. Juanola, E. Collantes, F. Leόn, A. Torres, M.J. García de Yébenes, R. Queiro, J. Gratacόs, E. García Criado, S. Giménez, L. Carmona
Journal: Annals of the Rheumatic Diseases (2014)

<h3>Objectives</h3> To design a strategy for early detection and referral of patients with suspected spondyloarthritis (SpA) by primary care physicians (PCP). <h3>Methods</h3> We used a modified RAND/UCLA methodology and systematic review (SR). A discussion group, formed by rheumatologists and PCP, discussed the process map and proposed recommendations and algorithms. These, together with the results of the SR, underwent 2 Delphi rounds to assess acceptance by a large group of users. <h3>Results</h3> The recommendations and grade of agreement are presnted in Table 1). <h3>Conclusions</h3> Any chronic (&gt;3 months) LBP in &lt;45 years patients should be investigated in 4 phases 1) key questions, 2) extra questions, 3) physical examination, and 4) additional tests. They should be referred to rheumatology if having 1) IBP, 2) signs suggestive of SpA, or 3) HLA B27+, elevated CRP, or sacroiliitis. Recommendations on the referral process are included. <h3>Acknowledgements</h3> This project was supported by a grant from MSD. <h3>Disclosure of Interest</h3> X. Juanola: None declared, E. Collantes: None declared, F. Leόn: None declared, A. Torres: None declared, M. J. García de Yébenes: None declared, R. Queiro: None declared, J. Gratacόs: None declared, E. García Criado: None declared, S. Giménez: None declared, L. Carmona Grant/research support: Abbvie, MSD, Roche, Speakers bureau: Roche, Pfizer <h3>DOI</h3> 10.1136/annrheumdis-2014-eular.1812
AB0965 Learning Curve in RAMRIS Scoring of Rheumatoid Hand Mri:
Authors: F. Barbieri, V. Tomatis, C. Cosso, E. Aleo, V. Prono, S. Migone, M. Cutolo, M.A. Cimmino
Journal: Annals of the Rheumatic Diseases (2014)

<h3>Background</h3> The "Rheumatoid Arthritis MRI Score" (RAMRIS) is a standardized method for evaluating MRI images of the hand and wrist of rheumatoid arthritis (RA) patients. Although widely used in research, it is associated with a long learning curve and considered time consuming. In addition, its good reproducibility may be limited to experienced users. <h3>Objectives</h3> We evaluated the proficiency of RAMRIS readings by two inexperienced readers before and after a brief training period. <h3>Methods</h3> Two sets of 12 MRIs each of hand and wrist of RA patients were used for the study. Patients of the two sets were matched for MRI disease severity. Pre- and post gadolinium Turbo 3D T1 sequences in the coronal plane with reconstruction in the axial plane and STIR sequences in the coronal and axial planes were obtained on a extremity-dedicated 0.2 T machine (Artoscan, Esaote, Genova, Italy). The RAMRIS reference (R) was the score given in agreement by two experienced readers (FB, MAC). Two rheumatology trainees graduated from 2 years and without direct experience in RAMRIS reading (A, B) were explained how to perform it and independently evaluated the first set of images using as reference the RAMRIS atlas. After one week, the MRIs of 6 of the patients of the first set and of 6 other patients were jointly evaluated and commented by all readers. Finally, A and B evaluated the second set of MRI images. The absolute differences in scores between R, A, and B were calculated for individual bones (erosions and bone marrow oedema, BME) in hand and wrist and for synovitis locations in the wrist only. <h3>Results</h3> The median per patient absolute differences with R was 3 (range 0-30) for A and 4 (range 0-30) for B, considering all 24 patients (p=0.019). Differences with R decreased between the first and second readings (A= from 4 (range 0-21) to 2 (range 0-30), p=0.06; B= from 7.5 (range 0-30) to 3 (range 0-21), p=0.0003). κ values compared with R are shown in table 1 for the individual lesions and total RAMRIS. The mean time necessary for reading the first and second set was 54.6±14.5 min and 48.8±8.3 min for A and 32.0±8.5 min and 29.6±1.4 min for B, respectively (both ns changes). <h3>Conclusions</h3> Ability in RAMRIS reading varied between observers according to the different lesion scored. A one week intensive training with readings of 12 MRIs of RA patients significantly increased the proficiency of inexperienced RAMRIS readers. <h3>Disclosure of Interest</h3> None declared <h3>DOI</h3> 10.1136/annrheumdis-2014-eular.2348
Abstract 197: Epigenetic regulation of miRNA expression in osteosarcoma
Authors: Magne Skarn, Heidi M. Namlos, Deeqa Ahmed, Guro E. Lind, Leonardo A. Meza-Zepeda, Ola Myklebost
Journal: Cancer Research (2012)

Abstract Epigenetic and genetic alterations of microRNAs (miRNAs) are frequently seen in cancer, and are responsible for the deregulation of differentiation and proliferation programs. The levels of transcription of miRNAs have been directly linked to epigenetic silencing, i.e. hypermethylation of CpG islands in tumors. Osteosarcoma is the most common primary malignant bone tumor and shows complex genomic aberrations. Using Illumina's Infinium technology we have profiled global promoter methylation of the EuroBoNeT osteosarcoma cell line panel (eurobonet.eu), in addition to a small panel of normal samples (osteoblast primary cultures and normal bone). A list of miRNAs that could be associated to a promoter CpG island was generated by identifying miRNAs that are encoded within transcripts of protein-coding host genes, or within 10 kb from a CpG island. Using an integrative approach, we have analyzed miRNA expression patterns together with DNA methylation data. Interestingly, hypermethylation of the upstream promoter seems to strongly suppress miRNA expression, and a high inverse correlation was observed between the degree of DNA methylation and expression of 17 miRNAs. The identified miRNAs were associated with hypermethylation in a high proportion of the osteosarcoma cell lines and hypomethylation in normal samples, suggesting that their transcription is regulated by promoter methylation, and that their silencing may play a role in osteosarcoma biology. To study this further, a subset of the cell lines was treated with a DNA demethylation agent. The relative expression levels of 8 miRNAs were found to increase upon treatment, as determined by quantitative RT-PCR. Thus, the transcription of these miRNAs seems to be regulated by epigenetic mechanisms. The methylation status of CpG islands associated with the most interesting miRNAs was then analyzed in more detail using methylation-specific PCR and direct bisulphite sequencing. We are currently expanding these investigations to a large tumor set where we will use quantitative methylation-specific PCR as a tool to determine the methylation status. Based on our findings, methylation of CpG islands seems to play a crucial role in controlling miRNA expression in osteosarcomas. This reveals new possibilities for activation of tumor-suppressing miRNAs by epigenetic treatment of osteosarcomas. 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 197. doi:1538-7445.AM2012-197
Removal of a migrated gastric band using the Soehendra bile stone lithotripter
Authors: Juan Gutiérrez, Fernando Acosta, Hector Geninazzi, Horacio Galiana
Journal: Endoscopy (2013)

A rare but disturbing complication of the placement of a laparoscopy-assisted gastric band (LAGB) is luminal migration into the stomach [1] [2]. Although there are various techniques described to remove a migrated band, most require expensive or specialized equipment, which is not always readily available [3] [4] [5]. Herein, we present a novel, simple and effective technique that was used to remove a migrated gastric band using the Soehendra lithotripter.
RELEVANCE OF THE CYP2C19 POLYMORPHISM FOR LOADING AND MAINTENANCE DOSE OF PRASUGREL AND CLOPIDOGREL TREATMENT EFFECT IN CORONARY ARTERY DISEASE PATIENTS UNDERGOING PERCUTANEOUS CORONARY INTERVENTION PCI : THE PRAISE-GENE STUDY
Authors: Moo Hyun Kim, Long Zhe Guo, Eun-Seok Shin, Soe Hee Ann, Sun Young Choi, Young Seok Lee, Tae Hyung Kim
Journal: Journal of the American College of Cardiology (2016)
Diffuse soft tissue uptake on a bone scan in a patient receiving alpha-interferon therapy.
Authors: Djamil Fertikh, Gary S. Greene
Journal: Clinical Nuclear Medicine (2002)

Alpha-interferon is an antiviral drug, often used to treat chronic viral hepatitis C (HCV). Many adverse reactions attributed to the drug have been described, but cases of polymyositis have been rare. The authors report a case of a symptomatic myopathy in a patient with chronic HCV treated with α-interferon as a rare cause of diffuse soft tissue uptake on a nuclear bone scan. Many causes have been described. However, a review of the literature revealed no similar cases.
Initial evaluation of a novel multibending backward-oblique viewing duodenoscope in endoscopic retrograde cholangiopancreatography
Authors: H. Imazu, K. Kanazawa, K. Ikeda, H. Kakutani, K. Sumiyama, T. Ang, S. Omar, H. Tajiri
Journal: Endoscopy (2011)

A novel multibending backward-oblique viewing duodenoscope was developed to overcome the difficult technical aspect of deep cannulation into the bile duct during endoscopic retrograde cholangiopancreatography (ERCP). The aim of the present study was to evaluate the initial experience of a novel multibending backward-oblique viewing duodenoscope (M-D scope) for ERCP. This was a retrospective review of 23 patients with native papilla who received biliary ERCP with the M-D scope between April and December 2010. The procedures were performed by two well-experienced endoscopists. In all patients, biliary cannulation and therapeutic procedure were successfully completed. In two patients with Billroth I gastrectomy, ERCP were initially attempted with a conventional single-bending duodenoscope, but biliary cannulations were unsuccessful. However, with the use of the M-D scope, biliary cannulation and therapeutic procedures were successfully completed. A novel multibending backward-oblique viewing duodenoscope is safe and feasible for therapeutic and diagnostic ERCP.
Allergic Rhinitis Symptoms in Infancy: Prevalence, Clinical Characteristics and Treatment
Authors: H.J. Chong Neto, N.A. Rosário, F.C. Silva, L.F.M. Bojarski, E.A. Grasselli, C.S. Rosario, F.H. Chong, B.A. Rosario
Journal: Journal of Allergy and Clinical Immunology (2012)
Abstract 4372: Evaluating TBK1 as a cancer therapeutic target in cancer cell lines with activated IRF3.
Authors: Asli Muvaffak, Qi Pan, Richard Middleton, Erick Morris, Rafael Fernandez, Jonwong Lim, Brian Dolinski, Thi T. Nguyen, Peter Strack, Haiyan Yan, Rossana Chung, Stephen Wu, Weiqun Zhang, Chris Hulton, Heather Hirsch, Kumiko Nagashimo, Yan Wang
Journal: Cancer Research (2013)

Abstract TBK1 is a non-canonical IκB protein kinase that phosphorylates and activates downstream targets such as IRF3 and cRel and, reportedly mediates NFkB activation in cancer. We used both genetic and pharmacological approaches to evaluate TBK1 function in cancer cells. In oncogenic KRAS mutant lung cancer cell lines, the TBK1 knockdown did not correlate with reduction in a 2D viability assay. Using TBK1 small molecule inhibitors, we found that the inhibition of cell growth in 2D viability assays did not correlate with Kras dependency or RAS genetic signature. Since the pIRF3(S386) levels in lung lines were too low to assess TBK1 target engagement, we identified cell lines with high pIRF3(S386) levels. We discovered a subset of pancreatic and colorectal cell lines that have high constitutive pIRF3(S386) levels and this correlated with high levels of pTBK1(S172). TBK1 inhibitors were able to dose-dependently inhibit pIRF3S386 in pancreatic &amp; colon lines. These observations indicate that pIRF3(S386) could be used as a biomarker for direct target engagement of TBK1 in cancer cell lines with activated TBK1 pathway. pTBK1(S172), a phosphorylation site within the TBK1 kinase domain activation loop, does not decrease upon inhibition with TBK1 inhibitors but, instead increases. This suggests stimulation of a feedback loop resulting in the activation of an upstream kinase(s) responsible for activating TBK1 in cancer cell lines. Although several pancreatic and colon cell lines were identified to have low μM sensitivity to TBK1 inhibitors, TBK1 shRNA knockdown did not impact proliferation in these cell lines even though pIRF3(S386) levels were reduced. Further studies using knockdown of the related IKKe homolog in cell lines with activated pathway are also being pursued to determine if IKKe knockdown alone or in combination with TBK1 knockdown would result in more substantial growth reduction. It is likely that inhibition of additional nodes in the NF-kB pathway and other pathways are needed to achieve robust anti-tumor efficacy. Citation Format: Asli Muvaffak, Qi Pan, Richard Middleton, Erick Morris, Rafael Fernandez, Jonwong Lim, Brian Dolinski, Thi T. Nguyen, Peter Strack, Haiyan Yan, Rossana Chung, Stephen Wu, Weiqun Zhang, Chris Hulton, Heather Hirsch, Kumiko Nagashimo, Yan Wang. Evaluating TBK1 as a cancer therapeutic target in cancer cell lines with activated IRF3. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 4372. doi:10.1158/1538-7445.AM2013-4372
Thinking tools: Acquired skills, cultural niche construction, and thinking with things
Authors: Ben Jeffares
Journal: Behavioral and Brain Sciences (2012)

Abstract The investigative strategy that Vaesen uses presumes that cognitive skills are to some extent hardwired; developmentally plastic traits would not provide the relevant comparative information. But recent views of cognition that stress external resources, and evolutionary accounts such as cultural niche construction, urge us to think carefully about the role of technology in shaping cognition.
Engineered in India — Patent Law 2.0
Authors: John J Castellani
Journal: New England Journal of Medicine (2013)

To the Editor: The intellectual-property system in India has severely deteriorated, and if left unchecked, it could affect patients not only in India but across the world. The assertion by Kapczynski in her Perspective article (Aug. 8 issue)1 that India should serve as a model for others does not withstand scrutiny and does a deep disservice to patients, doctors, and biopharmaceutical innovators in India and elsewhere. Our industry is predicated on research, progress, and hope. Innovative biopharmaceutical companies invest substantial resources in complex scientific endeavors to develop treatments and cures. Such investments rely on effective, predictable, and enforceable intellectual-property protections. . . .
EPICARDIAL FAT AND MAXIMAL FUNCTIONAL PERFORMANCE ASSESSED BY GAS EXCHANGE ANALYSIS IN A POPULATION OF PATIENTS AT RISK FOR CV EVENTS: A EURO-EX SUBSTUDY ANALYSIS
Authors: Marta Pellegrino, Vincenzo Tufaro, Greta Generati, Eleonora Alfonzetti, Francesco Bandera, Marco Guazzi
Journal: Journal of the American College of Cardiology (2016)
Source of Abnormal Bile in Patients with Cholesterol Gallstones
Authors: D. M. Small, S. Rapo
Journal: New England Journal of Medicine (1970)

Cholesterol gallstones are formed when excess cholesterol precipitates from bile supersaturated with cholesterol. Either the gallbladder, by alteration of the composition of normal hepatic bile, or the liver, by production of an abnormal bile, could be the source of the bile supersaturated by cholesterol. Since cholesterol gallstones are very prevalent among American Indians of the Southwest, we analyzed their gallbladder and hepatic bile to determine which organ is responsible for the disease. The composition of the liquid phase of gallbladder bile indicated that it was saturated with cholesterol, whereas the composition and physical state of hepatic bile indicated that it was a liquid highly supersaturated with cholesterol. Thus, in patients with cholesterol gallstones, the liver apparently secretes a bile supersaturated with cholesterol. This excess cholesterol is precipitated in the gallbladder, where this substance contributes to the production and continued growth of stones.
Abstract 4400: Blockade of Her2 binding to Hsp90 by emodin azide methyl anthraquinone derivative induces proteasomal degradation of Her2
Authors: Liwu Fu, Lisheng Zheng, Yan-yan Yan
Journal: Cancer Research (2011)

Abstract Overexpression of HER2/neu, a transmembrane tyrosine kinase acting as a coreceptor for other EGFR family members, is well known to be associated with a poor prognosis in cancer. In the present study, we observed that emodin AMAD, a novel emodin azide methyl anthraquinone derivative, extracted from the nature giant knotweed rhizome of traditional Chinese herbs, potently decreased Her2/neu protein in dose- and time-dependent manners and also inhibited the downstream MAPK and PI3K-Akt signaling pathway. Intriguingly, reserve transcription-PCR and protein turn-over assay revealed that the decrease of Her2/neu was independent of mRNA level but primarily owing to its protein stability. Meanwhile, proteasome inhibitor MG132 but not lysosome inhibitor chloroquine could restore Her2/neu and polyubiquitination of Her2/neu was augmented during emodin AMAD treatment. Furthermore, immunofluorescence study with anti-Her2/neu antibody showed that emodin AMAD disturbed the subcellular distribution of Her2/neu, with decreased location in the plasma membrane. Importantly, coimmunoprecipitation with anti-Hsp90 antibody revealed that emodin AMAD markedly impaired the binding between Hsp90 and Her2/neu. In addition, combination of emodin AMAD treatment and SiRNA against Her2 synergistically inhibited proliferation and induced apoptosis. Taken together, these data suggest that blockade of Her2/neu binding to Hsp90 and following proteasomal degradation of Her2/neu was involved in emodin AMAD-induced apoptosis in Her2/neu-overexpressing cancer cells. Our results provide suggestions that emodin AMAD could be promising as a new targeting therapeutic strategy in the treatment of Her2/neu-overexpressing cancers. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 4400. doi:10.1158/1538-7445.AM2011-4400