tbuckley/cabot-search huggingface dataset:
RUNX1 Upregulation by Cytotoxic Drugs Promotes Apoptosis
Authors: Daniel Speidel, Jasmin Wellbrock, Melissa Abas
Journal: Cancer Research (2017)

Mutations in the RUNX1 gene have been associated with chemotherapy resistance and poor prognosis in patients with acute myeloid leukemia (AML), T-cell acute lymphoblastic leukemia, and myelodysplastic syndromes. However, the underlying mechanisms connecting RUNX1 to the success of therapy remain elusive. Here we explore the hypothesis that RUNX1 is directly involved in the response of hematopoietic cells to cytotoxic agents. RUNX1 was upregulated posttranscriptionally by cytotoxic agents in C57BL/6 mice in vivo and hematopoietic cell lines. Upregulation was also seen in primary human AML cells after treatment with cytarabine in vitro Upon overexpression, RUNX1 restricted proliferation, promoted apoptosis, and augmented the DNA damage response. This unknown activity of RUNX1 required an intact runt homology domain (RHD), a domain where most leukemia-associated point mutations cluster. Consistent with this, two RHD-defective RUNX1 proteins lacked any antiproliferative or apoptotic activity, and RHD-defective (K83N, N109D) mutant RUNX1 conferred resistance to ionizing radiation when overexpressed in Ba/F3 cells under certain conditions. Our experiments reveal a novel function of RUNX1 and offer an explanation for the link between RUNX1 mutations and chemotherapy and radiation resistance. Moreover, these data suggest that pharmacologic modulation of RUNX1 might be an attractive new approach to treat hematologic malignancies. Cancer Res; 77(24); 6818-24. ©2017 AACR.
Cardiotoxicity and cardiac monitoring during adjuvant trastuzumab in daily Dutch practice.
Authors: Vivianne C. Tjan-Heijnen, Shanly C. Seferina, Maaike De Boer, Franchette W.P.J. van den Berkmortel, Roel JW Van Kampen, Agnes W Van de Wouw, Manuela A Joore, George F Borm, Adri C Voogd
Journal: Journal of Clinical Oncology (2013)

e11558 Background: In this study we assessed the cardiotoxic effects of adjuvant trastuzumab in daily practice after its introduction in the Netherlands in 2005. Methods: We included all patients with stage I-III breast cancer diagnosed in the years 2005 to 2007 in 5 hospitals in the South of the Netherlands. We studied guidelines adherence on left ventricular ejection fraction (LVEF) monitoring and the incidence of cardiotoxicity in patients with HER2 positive disease treated with adjuvant trastuzumab, using similar cardiac-endpoints as in prior randomized trials. In addition, we determined predictors of onset of cardiotoxicity. Results: Of 2685 patients included, 494 (18.4%) had a HER2 positive tumor. From these 494, 266 (53.8%) were treated with adjuvant chemotherapy and 228 (85.7%) received trastuzumab. Anthracycline based chemotherapy was given to 218 (96%) patients prior to trastuzumab treatment. LVEF measurements were done in 222 patients (97.4%). Fifty eight patients (25.4%) had ‘symptomatic cardiotoxicity’ during trastuzumab treatment, of whom 43 (18.9%) patients had a drop in LVEF of ≥ 10 percentage points. In 36 (15.8%) patients, cardiotoxicity led to permanent discontinuation of trastuzumab although in 50% LVEF recovered to levels permitting continuation, and in 22 (9.6%) patients treatment was temporary discontinued. No cardiac deaths were seen. The largest drops in LVEF occurred between baseline and the first 3-month assessment. Only 3.1% permanently discontinued treatment ≥ 6 months measurement. Patients with trastuzumab related cardiotoxicity did not show more cardiac comorbidities at baseline (14% vs. 24% p=0.12) and did not receive a higher cumulative dose of anthracyclines (mean 549mg vs. 546mg, p=0.48) than those without trastuzumab related cardiotoxicity. Conclusions: Regarding cardiotoxicity,trastuzumab was cautiously implemented in the Netherlands. In the first years, physicians based their decision to discontinue treatment frequently on patient ‘symptoms’ apart from LVEF outcome. Treatment discontinuation occurred mainly in the first three months after start of trastuzumab. Funding:Netherlands Organization for Health Research and Development and Roche Netherlands.
Haplotype-specific MAPT exon 3 expression regulated by common intronic polymorphisms associated with Parkinsonian disorders
Authors: Mang Ching Lai, Anne-Laure Bechy, Franziska Denk, Emma Collins, Maria Gavriliouk, Judith B. Zaugg, Brent J. Ryan, Richard Wade-Martins, Tara M. Caffrey
Journal: Molecular Neurodegeneration (2017)

Genome wide association studies have identified microtubule associated protein tau (MAPT) H1 haplotype single nucleotide polymorphisms (SNPs) as leading common risk variants for Parkinson's disease, progressive supranuclear palsy and corticobasal degeneration. The MAPT risk variants fall within a large 1.8 Mb region of high linkage disequilibrium, making it difficult to discern the functionally important risk variants. Here, we leverage the strong haplotype-specific expression of MAPT exon 3 to investigate the functionality of SNPs that fall within this H1 haplotype region of linkage disequilibrium.In this study, we dissect the molecular mechanisms by which haplotype-specific SNPs confer allele-specific effects on the alternative splicing of MAPT exon 3. Firstly, we use haplotype-hybrid whole-locus genomic MAPT vectors studies to identify functional SNPs. Next, we characterise the RNA-protein interactions at two loci by mass spectrometry. Lastly, we knockdown candidate splice factors to determine their effect on MAPT exon 3 using a novel allele-specific qPCR assay.Using whole-locus genomic DNA expression vectors to express MAPT haplotype variants, we demonstrate that rs17651213 regulates exon 3 inclusion in a haplotype-specific manner. We further investigated the functionality of this region using RNA-electrophoretic mobility shift assays to show differential RNA-protein complex formation at the H1 and H2 sequence variants of SNP rs17651213 and rs1800547 and subsequently identified candidate trans-acting splicing factors interacting with these functional SNPs sequences by RNA-protein pull-down experiment and mass spectrometry. Finally, gene knockdown of candidate splice factors identified by mass spectrometry demonstrate a role for hnRNP F and hnRNP Q in the haplotype-specific regulation of exon 3 inclusion.We identified common splice factors hnRNP F and hnRNP Q regulating the haplotype-specific splicing of MAPT exon 3 through intronic variants rs1800547 and rs17651213. This work demonstrates an integrated approach to characterise the functionality of risk variants in large regions of linkage disequilibrium.
Chlamydia trachomatis mutante en Dinamarca
Authors: S Hoffmann, J S Jensen
Journal: Eurosurveillance (2007)

En 2006 se detecto una variante mutante de Chlamydia trachomatis en Suecia y, desde entonces, se ha diagnosticado tambien en Noruega, pero no en Irlanda, ni en los Paises Bajos. En este documento se describe un estudio dirigido a valorar la presencia de la nueva variante en Dinamarca.
Comparison of Two Doses of lnterferon-Alpha-2b in Intravesical Prophylaxis of Superficial Bladder Tumors
Authors: Fernando Calais da Silva, Linhares Furtado, Mário Reis, Fernando Carreira, Vitor Dias, Gomes Oliveira, None Members of the Portuguese Genito-Urinary Group
Journal: European Urology (1995)
Evaluation of Fatigue in Previously Untreated CLL Patients with Comorbidities Treated with Obinutuzumab (GA101) + Chlorambucil (GClb) or Rituximab + Chlorambucil (RClb)
Authors: Valentin Goede, Peter C Trask, Katharina Ziesel, Marianne Uguen, Alexandra Bazeos, Kirsten Fischer, Michael Hallek
Journal: Blood (2016)
Abstract 20593: miR376c is Down Regulated in Thoracic Aortic Aneurysms in Marfan Syndrome
Authors: Elizabeth N Robertson, Stefanie S Portelli, Yaxin Lu, Andrew G Sherrah, Morvarid Emmani, Sanaz Maleki, Donna Lai, Michael Vallely, Michael Wilson, Paul Bannon, Murat Kekic, Cris G dos Remedios, Brett D Hambly, Richmond W Jeremy
Journal: Circulation (2016)

Thoracic aortic aneurysms (TAA) in Marfan syndrome (MFS) are associated with an increase in TGF-β in the aortic wall. Changes in post-transcriptional modifiers, such as miRNA, can lead to altered expression of signaling proteins. We hypothesized that altered expression of miRNA occur in MFS, leading to aberrant post-transcriptional regulation of gene expression for signaling proteins, such as TGF-β, that interact with the variant fibrillin in MFS. Total RNA was isolated from aortic tissue collected at time of surgery and snap frozen in liquid nitrogen, from 3 MFS patients with aortic dilatation (1F, 2M; Age 36±18yrs; Ao Diameter 47±3mm) and 3 controls (2F, 1M; Age 45±8yrs). The RNA was reverse transcribed with custom primers for 31 pre-selected miRNA, that were chosen from a list of altered miRNA identified on a microarray performed on peripheral blood of patients with MFS. qPCR was performed on the subsequent cDNA using a custom TaqMan® Array Card (ThermoFisher). miRNA expression was considered to be significantly altered if there was >±2 fold change (p
“Hyped” papers by disgraced Karolinska surgeon should be retracted, says ethics board
Authors: Nigel Hawkes
Journal: BMJ (2017)

Sweden’s top ethical review board has called for six papers published by the disgraced surgeon Paolo Macchiarini to be retracted.

They include a key 2011 paper published in the Lancet in which Macchiarini and colleagues claimed success in transplanting an artificial trachea seeded with the patient’s own cells into a 36 year old man.1 The operation took place at the Karolinska University Hospital in Stockholm.

Since doubts first emerged about Macchiarini’s work, a series of reviews has been carried out.23 At first the Karolinska Institute, which employed him, declined to accept that there was evidence of misconduct but was …
Genotype/Phenotype Correlations in 103 Children from 87 Families with Hereditary Spherocytosis
Authors: Jakob Pugi, Luke J. Drury, Jacob C. Langer, Sheila Butchart, Michelle Fantauzzi, Jillian Baker, Victor S. Blanchette, Melanie Ann Kirby-Allen, Manuel Carcao
Journal: Blood (2016)
Vigilancia de la gripe en Europa entre octubre de 1999 y febrero de 2000
Authors: K Mantey, A Mosnier
Journal: Eurosurveillance (2000)

La vigilancia de la gripe realizada mediante el Sistema Europeo para la Vigilancia de la Gripe (European Influenza Surveillance Scheme; -EISS-) durante la temporada invernal 1999-2000 ha puesto de manifiesto que la gripe afecto a la mayoria de los 11 paises participantes y que su mayor actividad se observo en diciembre de 1999 y en enero de 2000. El virus de la gripe A(H3N2), responsable de una de las tres grandes epidemias de los ultimos diez anos en algunos paises de la region EISS, circulo ampliamente. En Belgica, la Republica Checa, Francia, Alemania, Italia, Paises Bajos, Espana y Suiza se registro una actividad generalizada. La falta de una definicion unica de caso sigue siendo un obstaculo para la comparacion de datos y una de las prioridades clave para el desarrollo del EISS es estandarizar, de forma inmediata, los principales indicadores recogidos y los umbrales epidemicos.
Adverse Outcomes of Reducing Foreign Aid for HIV Programs
Authors: M.J. Friedrich
Journal: JAMA (2017)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA HomeNew OnlineCurrent IssueFor Authors Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA journal
The Progression of Geographic Atrophy Secondary to Age-Related Macular Degeneration
Authors: Monika Fleckenstein, Paul Mitchell, K. Bailey Freund, SriniVas Sadda, Frank G. Holz, Christopher Brittain, Erin C. Henry, Daniela Ferrara
Journal: Ophthalmology (2017)

Geographic atrophy (GA) is an advanced form of age-related macular degeneration (AMD) that leads to progressive and irreversible loss of visual function. Geographic atrophy is defined by the presence of sharply demarcated atrophic lesions of the outer retina, resulting from loss of photoreceptors, retinal pigment epithelium (RPE), and underlying choriocapillaris. These lesions typically appear first in the perifoveal macula, initially sparing the foveal center, and over time often expand and coalesce to include the fovea. Although the kinetics of GA progression are highly variable among individual patients, a growing body of evidence suggests that specific characteristics may be important in predicting disease progression and outcomes. This review synthesizes current understanding of GA progression in AMD and the factors known or postulated to be relevant to GA lesion enlargement, including both affected and fellow eye characteristics. In addition, the roles of genetic, environmental, and demographic factors in GA lesion enlargement are discussed. Overall, GA progression rates reported in the literature for total study populations range from 0.53 to 2.6 mm2/year (median, ∼1.78 mm2/year), assessed primarily by color fundus photography or fundus autofluorescence (FAF) imaging. Several factors that could inform an individual's disease prognosis have been replicated in multiple cohorts: baseline lesion size, lesion location, multifocality, FAF patterns, and fellow eye status. Because best-corrected visual acuity does not correspond directly to GA lesion enlargement due to possible foveal sparing, alternative assessments are being explored to capture the relationship between anatomic progression and visual function decline, including microperimetry, low-luminance visual acuity, reading speed assessments, and patient-reported outcomes. Understanding GA progression and its individual variability is critical in the design of clinical studies, in the interpretation and application of clinical trial results, and for counseling patients on how disease progression may affect their individual prognosis.
TCT-530 The combination of rosuvastatin (10mg) and eicosapentaenoic acid (1800mg) improved native coronary plaques &gt; 5.7 years after stent implantation
Authors: Youichirou Sugizaki, Hiromasa Otake, Toshiro Shinke, Hiroyuki Kawamori, Koji Kuroda, Takayoshi Toba, Yuto Shinkura, Yuichiro Nagano, Hiroyuki Yamamoto, Hiroyuki Onishi
Journal: Journal of the American College of Cardiology (2017)
Interrupção da transmissão do sarampo em Gipuzkoa (País Basco), Espanha
Authors: G Cilla, M Basterretxea, J Artieda, D Vicente, E Pérez-Trallero
Journal: Eurosurveillance (2004)

A vacina do sarampo foi introduzida em Gipuzkoa (Pais Basco, Espanha) em 1978 e foi substituida pela vacina do sarampo, papeira e rubeola (MMR) para criancas dos 12 a 15 meses em 1981. Em 1992 foi introduzida uma segunda dose da vacina MMR. As duas doses da vacina MMR foram bem aceites pela populacao, tendo-se obtido uma cobertura elevada (95% e 91% para a primeira e segunda doses, respectivamente, para o periodo de 1993 a 2002). A circulacao do virus do sarampo foi interrompida na segunda metade dos anos noventa: nao foi notificado nenhum caso do sarampo indigena entre 1998 e 2003 e foram apenas confirmados casos importados durante este periodo. Estes dados indicam que o prgrama de vacinacao contra o sarampo implementado foi eficaz. Nao obstante, para se evitarem epidemias do sarampo apos a introducao viral, e necessario manter niveis elevados de cobertura da vacina MMR para as duas doses (g95%).
Characterization of HER family receptor expression and activation in 15 human mammary tumors
Authors: Kartiki V. Desai, Justin L. Simmons, Antonio Fargiano, Gert Van Den Eynden, Peter B. Vermeulen, Luc Y. Dirix, Maria Merino, Jeffrey E. Green
Journal: Cancer Research (2005)

1893   Numerous studies have shown that overexpression of the human epidermal growth factor receptor type 2 (HER2/erbB2) is associated with poor prognosis of breast cancer. HER2 overexpression is now used as a diagnostic marker to select patients for antibody therapy with trastuzumab. In addition, HER2 may play an important role in tumor growth even when not overexpressed: being the preferred dimerization partner for other HER family members it can effectively boost anti-apoptotic and proliferation-stimulating signaling by growth-factor-activated receptors like HER1/EGFR and HER3. Pertuzumab is the first in a new class of targeted therapeutic agents known as HER dimerization inhibitors (HDIs) and is currently undergoing clinical testing in several phase II trials (Franklin et al., 2004). Previous studies using human tumor xenografts grown on nude mice indicated that the presence of HER2-containing heterodimers (HER2hd) correlated with response to pertuzumab treatment (Bossenmaier et al., 2004). These results suggest assessing patient tumors for possible indicators of HER2 activation that, in future studies, could be evaluated as response prediction markers. Here we investigated 15 freshly resected mammary tumors from untreated patients by immunohistochemistry, immunoprecipitation (IP) and Western blotting (WB) techniques. In particular, expression of HER family receptors, HER2 phosphorylation (pHER2) and HER2hd were assayed. From 5 patients, axillary lymph node metastases were available for analyses and comparison with the respective primary tumors. Our results confirm that IP/WB is a sensitive method to detect and quantify HER-family receptor proteins and HER2hd in nearly all patient tumor lysates. Receptor mRNA was compared to the respective protein expression and the presence of HER2hd complexes. Furthermore, the co-presence of HER2hd and pHER2, both of which would indicate activated HER2, was not always observed and was not predicted by receptor expression. In a subset of 5 patients, 3 lymph node metastases showed higher HER2 expression, increased HER2hd and elevated pHER2 compared to the respective primary tumors. Only one of the primary tumors indicated enhanced HER2 activation compared to the lymph node metastasis from the same patient at time of surgery. In conclusion, different markers of HER2 activation are expressed at different levels in primary breast cancer and there is a clear trend toward increased activation signals in lymph node metastases. The presence of HER2hd does not perfectly correlate with pHER2 and HER2 protein expression. The parameter most reliably predicting response to HER2-targeting therapies remains to be determined in future clinical trials.
Clinical Management of Insomnia Disorder
Authors: Daniel J. Buysse, A. John Rush, Charles F. Reynolds
Journal: JAMA (2017)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA HomeNew OnlineCurrent IssueFor Authors Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA journal
Implications of Elevated C‐Reactive Protein and Serum Amyloid A Levels in IgG4‐Related Disease: Comment on the Article by Perugino et al
Authors: A. Faiz Karim, Laura E. M. Eurelings, P. Martin van Hagen, Jan A. M. van Laar
Journal: Arthritis & Rheumatology (2017)

We read with great interest the published article by Perugino et al (1) providing an excellent overview on IgG4-related disease (IgG4-RD). However, the authors have not included the value of C-reactive protein (CRP) in IgG4-RD and the potential secondary complications due to this. Herewith, we want to highlight the clinical relevance of elevated CRP in IgG4-RD.

This article is protected by copyright. All rights reserved.
Epidemiología de las infecciones asociadas a Streptococcus pyogenes en Europa
Authors: T L Lamagni, A Efstratiou, J Vuopio-Varkila, A Jasir, C Schalén
Journal: Eurosurveillance (2005)

A finales de los anos 80, varios paises europeos notificaron brotes de enfermedad grave producida por Streptococcus pyogenes. Esto marco el inicio de un nuevo periodo tras decadas previas, donde se habian notificado muy pocos brotes de estas caracteristicas. Estos cambios en la ocurrencia de la enfermedad formaron parte de un fenomeno global, cuyas razones aun tienen que ser explicadas. Los resultados de las actividades de vigilancia de las infecciones invasivas por S. pyogenes dentro de Europa en los ultimos 15 anos identificaron un incremento en muchos paises. Sin embargo, las diferencias entre los metodos de vigilancia de los paises hacen dificiles las comparaciones, lo que demuestra la necesidad de una estrategia unificada de vigilancia en toda Europa. El Programa Strep-EURO se introdujo en 2002 para responder a tal necesidad.
TCT-62 Thirty-Day Readmissions After Endovascular or Surgical Revascularization for Chronic Mesenteric Ischemia: Insights from the National Readmissions Database
Authors: Fabio Lima, Dhaval Kolte, David Louis, Kevin Kennedy, J. Dawn Abbott, Peter Soukas, Omar Hyder, Shafiq Mamdani, Herbert Aronow
Journal: Journal of the American College of Cardiology (2017)
TCT-543 Long-term outcome after successful MitraClip implantation in high-risk patients
Authors: Edith Lubos, Eike Tigges, Daniel Kalbacher, Christina Thomas, Florian Deuschl, Niklas Schofer, Lenard Conradi, Johannes Schirmer, Ulrich Schäfer, Hermann Reichenspurner, Stefan Blankenberg
Journal: Journal of the American College of Cardiology (2017)