tbuckley/cabot-search huggingface dataset:
469 GENETIC MAPPING QUANTITATIVE TRAIT LOCI FOR HOST CONTROL OF HBV VIRAL LOAD IN THE HLA REGION AMONG FAMILIES OF HEPATOCELLULAR CARCINOMA
Authors: W.-Y. Kao, S.-Y. Chou, J.-W. Jian, P.-J. Chen, C.-L. Lin, C.-J. Liu, Y.-F. Liaw, S.-M. Lin, S.-D. Lee, M.-W. Yu
Journal: Journal of Hepatology (2012)
A1.82 Limited role of microrna 155 innate immunity dependent arthritis
Authors: Eliana Goncalves-Alves, Victoria Saferding, Antonia Puchner, Josef Smolen, Kurt Redlich, Stephan Blüml
Journal: Annals of the Rheumatic Diseases (2014)

<h3>Background</h3> MicroRNA 155 (miR155) has been demonstrated to be essential for the development of collagen induced arthritis by controlling the generation of autoreactive T and B cells. However, the contribution of miR155 in innate immune cells is not known. <h3>Materials and Methods</h3> We analysed activation and cytokine production of macrophages and dendritic cells (DCs) <i>in vitro</i> and <i>in vivo</i>. We analysed T-cells stimulatory capacity of DCs. We crossed miR155 deficient mice into hTNFtg mice and analysed arthritis development clinically as well as histologically. <h3>Results</h3> MiR155 deficiency did not alter the differentiation of BMDC from bone marrow cells or the expression of costimulatory molecules or MHCII expression after stimulation of macrophages and DCs <i>in vitro</i> and <i>in vivo</i>. Proinflammatory cytokine production (IL-12p40, IL-6) after LPS challenge in <i>vivo</i> was not different in serum of wt mice and miR155<sup>-/-</sup>mice. We also Facs-sorted DCs after stimulation with LPS in vivo and determined the production of proinflammatory cytokines such as IL-23, IL-6 as well as TNF. We did not detect differences between wt and miR155<sup>-/-</sup> mice. In addition, the T cell stimulatory capacity of wt and miR155<sup>-/-</sup>was identical <i>in vitro</i> and <i>in vivo</i>. When we analysed miR155<sup>-/-</sup>mice compared to wt mice in the hTNFtg model of inflammatory arthritis, which is independent of the adaptive immune system, we did not detect differences in the clinical signs and symptoms of arthritis. Histologically, we even found slightly increased synovial inflammation in hTNFtg/ miR155<sup>-/-</sup>mice compared to wt mice. <h3>Conclusion</h3> In contrast to the pivotal role of miR155 in autoimmunity requiring the adaptive immune system, the role of miR155 in innate immunity seems to be limited. This is emphasised by the fact that miR155 hardly influences the course of TNF-driven arthritis, which is mainly dependent on components of the innate immune system.
On the Road (to a Cure?) — Stem-Cell Tourism and Lessons for Gene Editing
Authors: R. Alta Charo
Journal: New England Journal of Medicine (2016)

Interview with Prof. R. Alta Charo on recent advances in gene editing and concerns about medical tourism. (11:24)Download Many desperate patients have left the United States seeking unproven and risky stem-cell interventions available in countries with less rigorous regulation. How can we keep gene editing from triggering a new wave of medical tourism?
Klippel-Feil Syndrome With Spinal Dysraphism
Authors: Emmanuel W. Hudson, William Makis
Journal: Clinical Nuclear Medicine (2016)

A 49-year-old woman with known Klippel-Feil syndrome had a CT scan for staging of stage IIIA invasive carcinoma of the left breast. She was found to have cervicothoracic spinal dysraphism with diastematomyelia. An F-NaF bone PET done as part of the metastatic workup showed the characteristic sagittal bone spur, and MRI demonstrated a complete split of the cervical and upper thoracic spinal cord, previously unknown to the patient.
Seroprevalence of hantavirus infections in Switzerland in 2009: difficulties in determining prevalence in a country with low endemicity
Authors: O Engler, J Klingström, E Aliyev, C Niederhauser, S Fontana, M Strasser, J Portmann, J Signer, S Bankoul, F Frey, C Hatz, A Stutz, A Tschaggelar, M Mütsch
Journal: Eurosurveillance (2013)

Binary file ES_Abstracts_Final_ECDC.txt matches
CULPRIT VERSUS MULTIVESSEL 1-STAGE PERCUTANEOUS CORONARY INTERVENTION IN ST ELEVATION MYOCARDIAL INFARCTION: A SYSTEMATIC REVIEW AND META-ANALYSIS OF RANDOMIZED CONTROL TRIALS
Authors: Pedro Villablanca Spinetto, David Briceno, Joseph Donnelly, Cesar Guerrero-Miranda, Salvador Villablanca, Vankeepuram Srinivas, Mark Menegus, Anna Bortnick, Michael Johnson, Ernest Monrad, Mark Greenberg, David Slovut, Robert Pyo
Journal: Journal of the American College of Cardiology (2015)
Evaluation of Pulmonary Hypertension and Surgical Outcome by Dynamic Pulmonary Perfusion Imaging in Patients With Valvular Disease
Authors: Xuemei Wang, Rongfang Shi, Shiwei Pan, Wei Fang
Journal: Clinical Nuclear Medicine (2011)

The gold standard for assessing the degree of pulmonary hypertension is by right ventricular catheterization, an invasive procedure. This study was carried out to evaluate a noninvasive method using dynamic pulmonary perfusion imaging (DPPI) for assessing pulmonary hypertension and surgical outcome in patients with valvular heart disease.A total of 116 patients (50 men, 66 women, mean age: 45.8 ± 10.7 years) with valvular disease and 10 healthy volunteers (4 men, 6 women; mean age: 40.2 ± 12.8 years) were included in this study. Baseline DPPI with Tc-99m macroaggregated albumin and right ventricular catheterization were performed in all patients, before mitral valve replacement with or without aortic valve replacement surgery, and healthy volunteers. At 7 to 14 days postsurgery, 105 patients were re-evaluated with DPPI. A total lung region of interest was used to calculate a time-activity curve from the DPPI. The lung equilibrium time (LET: time from Tc-99m macroaggregated albumin entering the lungs to equilibrium) was measured. Receiver operating characteristic analysis of LET for diagnosing pulmonary hypertension was carried out.LET in patients with valvular heart disease was significantly prolonged compared with those in 10 healthy volunteers (P < 0.001). LET was 14.79 ± 4.37 seconds and 27.78 ± 10.26 seconds in 10 healthy volunteers and patients, respectively). A strong correlation between LET and mean pulmonary arterial pressure (r = 0.827, P < 0.001) was found. Using mean pulmonary arterial pressure as a gold standard and threshold value of LET at 22.7 seconds, the sensitivity and specificity of LET for assessing pulmonary hypertension were found to be 94.7% and 78.0%, respectively. The pre- and postsurgery LET were found to be significantly different (27.48 ± 9.83 seconds vs. 21.33 ± 6.18 seconds, P < 0.001).DPPI is an accurate and noninvasive method for evaluating pulmonary hypertension and surgical outcome in patients with valvular heart disease.
Abstract 3476: Hyaluronan-mediated motility receptor as a novel target for inhibiting glioblastoma stem cells
Authors: Mingyao Ying, Jessica Tilghman, John Laterra
Journal: Cancer Research (2012)

Abstract Introduction: Glioblastoma stem cells (GSCs) are a subpopulation of tumor cells that promote tumor invasion and angiogenesis, therapeutic resistance and tumor recurrence. Here, we study the function of hyaluronan-mediated motility receptor (HMMR) in human GSCs. HMMR is hyper-expressed in human glioblastoma samples relative to lower-grade glioma and non-neoplastic specimens. Hyper-expression of HMMR also correlates with poor survival in glioma patients. HMMR is a multifunctional oncogenic protein that plays essential roles in tumorgenesis. Extracellular HMMR forms a complex with CD44 that upon binding to hyaluronan activates intracellular signaling pathways that regulate tumor cell survival, proliferation and invasion. Intracellular HMMR associates with microtubules, interacts with the mitotic spindle and contributes to tumor progression by promoting genomic instability. HMMR and CD44 are two ubiquitous receptors for hyaluronan, which is a prominent component of the microenvironment in most malignant tumors. CD44 has been identified as a cancer stem cell marker and CD44 directly regulates cancer stem cells in a variety of cancers including glioblastoma. Critical evidence regarding the function of HMMR in actual glioblastoma tumors and in the context of tumor-initiating GSCs is still lacking. Results: We found that HMMR is ubiquitously expressed in a panel of human glioblastoma-derived neurosphere cultures that are enriched for GSCs. Targeting HMMR by lentivirus-mediated shRNA delivery potently disrupted in vitro self-renewal of GSCs and inhibited the expression of key GSC markers, such as CD133, SOX2 and Olig2. HMMR knockdown also blocked the in vivo tumorigenic potential of GSCs in mouse orthotopic xenograft model. Notably, disruption of HMMR in GSCs attenuated the activity of Notch signaling, which supports the cancer stem cell hierarchy in glioblastoma and various other cancer types. Significance: This research identifies HMMR as a novel therapeutic target in the treatment of glioblastoma by depleting the tumor-initiating GSCs. It also introduces a novel hypothesis regarding the mechanistic crosstalk between HMMR-mediated signaling and Notch signaling pathway. Understanding this crosstalk between HMMR and Notch signaling will have a significant impact on current efforts to target Notch driven mechanisms for GBM therapy. Overall, these studies will lay an essential foundation for the development of HMMR-targeting strategies, such as HMMR inhibitors or monoclonal antibodies, as new therapeutic approaches targeting glioblastoma. 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 3476. doi:1538-7445.AM2012-3476
Conflict of interest in the Times
Authors: R. Smith
Journal: BMJ (1995)

Doctors who offer advice through the media may be tempted to be somewhat cavalier as they are not dealing with individual patients. But many people continue to take very seriously what these doctors have to say. Doctor journalists must therefore be careful what they write, not leastbecause other doctors can analyse their advice.

Dr Thomas Stuttaford, a former Tory member of parliament, has written for the Times for many years and has cultivated an image of the amiable, avuncular, home counties doctor who may not be quite at the cutting edge but who can be relied upon for solid advice. In reality, as he told us in an article published last week in the Times (16 May, p 15), Dr Stuttaford has worked with BUPA, the “brand leader” in medical screening, for 25 years. By telling us this he might be said to have declared his conflict of interest for writing a long piece on screening, but unfortunately the declaration appears in the 12th paragraph and has nothing like the prominence of the headings: “Dr …
TRIDIONE THERAPY
Authors: MEYER A. PERLSTEIN
Journal: American Journal of Psychiatry (1947)

1. A progress report of clinical observations in the therapeutic use of tridione on 136 cases of varied neurological manifestations, over a period of 2 years, is presented. 2. As previously reported, most spectacular benefits were obtained in cases of petit mal, where clinical improvement was immediate, associated with improvement in [SEE TABLE2 IN SOURCE PDF] the EEG pattern, and sustained often after cessation of the drug. 3. Tridione appears to be useful as an adjuvant drug in the treatment of grand mal seizures, though it does seem to aggravate some cases. 4. Both grand and petit mal of the idiopathic type were more responsive than those due to organic lesions. 5. Anticonvulsant action is indicated by its beneficial effects in cases of tetanus. 6. Tridione is of value in cerebral palsy, especially for reducing tension of the athetoid type. 7. Some forms of behavior disturbances are sedated by tridione. 8. Site of action for tridione appears to be the midbrain and (with some selectivity) the basal nuclei, an inference drawn from its failure to help patients with pyramidal lesions, while markedly benefiting extra-pyramidal lesions, with the exception of chorea, parkinsonism, and dystonia. 9. Toxic side-effects in the use of tridione, in our experience, were rare in children, were generally innocuous, and seemed readily reversible with cessation of the drug. More severe reactions were seen in adults.
Re: Relationship Between Environmental Tobacco Smoke Exposure and Carcinogen-Hemoglobin Adduct Levels in Nonsmokers
Authors: MARK J. REASOR
Journal: JNCI Journal of the National Cancer Institute (1993)

Journal Article Re: Relationship Between Environmental Tobacco Smoke Exposure and Carcinogen-Hemoglobin Adduct Levels in Nonsmokers Get access MARK J. REASOR MARK J. REASOR Search for other works by this author on: Oxford Academic PubMed Google Scholar JNCI: Journal of the National Cancer Institute, Volume 85, Issue 20, 20 October 1993, Pages 1693–1694, https://doi.org/10.1093/jnci/85.20.1693-a Published: 20 October 1993
Abstract 2583: Regulation of AKT-FoxO signaling by PKG2 inhibits colon cancer cell growth.
Authors: Rui Wang, In-Kiu Kwon, Muhan Hu, Darren D. Browning
Journal: Cancer Research (2013)

Abstract Signaling through cGMP has emerged as a potentially important suppressor of tumorigenesis in the colon, but the mechanism is poorly defined. Studies of guanylyl-cyclase (GCC) knockout mice indicate that cGMP signaling suppresses proliferation in the colon epithelium, and more recently that inhibition of AKT has an important role. Type-2 cGMP-dependent protein kinase (PKG2) is a central effector of cGMP in the colon epithelium and is a likely mediator of the homeostatic effects of cGMP signaling. The present study sought to determine whether PKG2 can regulate AKT signaling in colon cancer cells and in the colon mucosa. Activation of PKG2 in LS174T and HT29 colon cancer cells inhibited cell proliferation and increased G1 arrest. PKG2 activation also inhibited AKT activity in these cells as determined by immunoblotting for phospho-AKT and downstream phospho-S6. Suggestive of a mechanism, analysis of upstream components revealed that PKG2 increased the levels of phosphatase and tensin homolog (PTEN). Central to the growth-promoting role of AKT signaling is the inactivation of forkhead transcription factors (FoxO), which regulate growth-inhibitory and pro-apoptotic target gene expression. Consistent with the inhibition of AKT signaling, activation of PKG2 significantly increased luciferase reporter activity driven by FoxO-responsive elements in colon cancer cells. This activation was associated with increased levels of several FoxO target genes, including catalase, p27kip. The regulation of AKT/FoxO pathway by PKG2 in vivo was supported by increased phospho-AKT levels, and reduced FoxO target gene expression in the colon mucosa of Prkg2-/- mice compared to wild type siblings. Moreover, activation of cGMP signaling in the colon mucosa led to increased expression of FoxO targets, and suppression of both proliferation and redox stress. Taken together these data define a novel signaling pathway in the colon epithelium, where of PKG2 leads to activation of FoxO. The established tumor suppressor role of the FoxO proteins highlights the potential therapeutic role for cGMP signaling in the prevention of colon cancer. Citation Format: Rui Wang, In-Kiu Kwon, Muhan Hu, Darren D. Browning. Regulation of AKT-FoxO signaling by PKG2 inhibits colon cancer cell growth. [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 2583. doi:10.1158/1538-7445.AM2013-2583
A6.04 CRISPR/CAS9 mediated genome engineering of human mesenchymal stem cells
Authors: G van den Akker, H van Beuningen, E Blaney Davidson, P van der Kraan
Journal: Annals of the Rheumatic Diseases (2016)

<h3>Background and objectives</h3> CRISPR/Cas9 is a novel technique for genomic inactivation of genes. In this study we assessed the feasibility of generating knock-out cell populations from human mesenchymal stem cells, without sub-cloning of cells. <h3>Materials and methods</h3> CRISPR guide RNAs were designed and cloned into a lentiviral Cas9 expression system. HEK293 cells or MSC were transduced with lentivirus and selected with puromycin. CRISPR efficiency for genomic modification was determined by genomic PCR, surveyor nuclease digestion while protein expression was assessed by immunoblotting. <h3>Results</h3> Transforming Growth Factor β (TGFβ) signalling is crucial for chondrogenic differentiation of MSC and the maintenance of the articular chondrocyte phenotype. Currently the exact role of individual downstream SMAD transcription factors is unknown. Efficient RNA interference mediated knock-down of SMAD proteins might still allow signal transduction via the remaining SMAD protein. To generate knock-out cell populations, CRISPRs (guide RNAs) were designed to target the second coding exon of the five R-SMAD genes. The CRISPR efficiency was assessed using the surveyor nuclease assay on HEK293 cells and MSC. The evaluated CRISPRs had a variable efficiency in HEK293 cells: 20–90% genomic modification of the target gene was observed. Increasing the viral load (MOI) clearly improved this efficiency in MSC, while increased antibiotic selection pressure did not. To further improve the on-target efficiency we used a double guide RNA targeting strategy to excise a 100 base pair fragment. By regular PCR it was estimated that 25% of the total cell population carried the truncated form of the gene. The surveyor nuclease assay showed an even higher percentage of genomic modification. Importantly, this double targeting strategy decreased SMAD protein expression in HEK293T by 90%. MSC were expected to be more vulnerable to CRISPR/Cas9 genome engineering and/or high viral loads. Following careful optimisation of lentiviral transduction and antibiotic selection protocols for MSC, we evaluated the effect of four control CRISPR/Cas9 constructs targeting GFP. Our preliminary findings indicate that MSC stably expressing CRISPR/Cas9 exhibit normal differentiation characteristics. <h3>Conclusions</h3> We show that efficient targeting of genes using CRISPR/Cas9 in MSC cell populations, leading to strongly decreased protein expression, is feasible without clonal selection.
Abstract 3397: Synergistic activity of the Akt inhibitor perifosine and 5-fluorouracil in 5-FU resistant gastric cancer.
Authors: Kim Hyo Song, You Keun Shin, Xianglan Zhang, Jung Min Kim Kim, Tae Soo Kim, Chan Hee Park, Woo Ick Jang, Juergen Engel, Sun Young Rha Rha
Journal: Cancer Research (2013)

Abstract Purpose Akt/PI3K pathway has been known to confer resistance to conventional chemotherapy. Perifosine is a synthetic novel alkylophospholid which inhibits Akt activation. Because 5-fluorouracil (5-FU) is a common cytotoxic agent used in gastric cancer, we evaluated the role of perifosine overcoming 5-FU chemoresistance. Experimental design We checked the correlation between pAkt expression and 5-FU sensitivity in 25 gastric cancer cell lines. Cytotoxic effects of 5-FU and perifosine combination were assessed using in vitro assays (cell growth and apoptosis analysis). Whether this synergistic combination of two drugs has significant effect on their downstram targets and on biochemical markers were also tested with western blotting analysis. Tumor inhibition and pAkt expression were measured using xenograft mice treated with perifosine and 5-FU combination. Results More 5-FU resistant cell lines demonstrated higher pAkt expression levels (mean 1.35 IU vs 0.49 IU, p=0.019). Among the 14 5-FU resistant cell lines, majority of the cell lines (57.1%) showed synergistic effect with perifosine combination. Perifosine and 5-FU combination caused marked Akt and extracellular signal-regulated kinase (Erk) 1/2 dephosphorylation in synergistic cell line. Moreover, combination results in a substantial induction of apoptosis by JNK pathway activation in synergistic cell line. In vivo model, treatment with tolerated doses of 5-FU derivatives, capecitabine and perifosine resulted in significantly enhanced antitumor efficacy relative to that of either agent alone (P=0.006). Histopathologic analysis of pAkt expression also revealed prominent pAkt reduction in combination groups. In the gene expression profiling analysis, Akt1 and MAPK4K genes were up-regulated in synergistic cell lines implicating those genes as predictive markers for restoring 5-FU resistance in combination treatment. Conclusions These results indicate that activated Akt pathway confers 5-FU chemoresistance. In addition, perifosine and 5-FU combination restored those chemoresistance via pAkt, pErk dephosphorylation and JNK activation. Taken together, 5-FU and perifosine combination may be a promising therapeutic strategy to improve patient outcome in gastric cancer patients. Citation Format: Kim Hyo Song, You Keun Shin, Xianglan Zhang, Jung Min Kim Kim, Tae Soo Kim, Chan Hee Park, Woo Ick Jang, Juergen Engel, Sun Young Rha Rha. Synergistic activity of the Akt inhibitor perifosine and 5-fluorouracil in 5-FU resistant gastric cancer. [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 3397. doi:10.1158/1538-7445.AM2013-3397 Note: This abstract was not presented at the AACR Annual Meeting 2013 because the presenter was unable to attend.
DOES STATIN THERAPY PREVENT NEOATHEROSCLEROSIS?
Authors: Sining Hu, Haibo Jia, Rocco Vergallo, Jinwei Tian, Tsunenari Soeda, Yoshiyasu Minami, Lei Gao, Daniel Ong, Hang Lee, Shaosong Zhang, Bo Yu, Ik-Kyung Jang
Journal: Journal of the American College of Cardiology (2015)
A Case of Olfactory Neuroblastoma Detected by 18F-FDG PET/CT
Authors: Kenichi Tanaka, Yuka Yamamoto, Hiroshi Hoshikawa, Yoshihiro Nishiyama
Journal: Clinical Nuclear Medicine (2014)

Olfactory neuroblastoma is an uncommon malignant neoplasm of the superior nasal cavity. We report a case of a 78-year-old woman who presented with frontal headache and proptosis of the right eye. CT revealed a nasoethmoid mass with diffuse calcifications. FDG PET/CT demonstrated intense FDG uptake by a main nasoethmoid tumor and metastatic lesions in the cervical lymph nodes. Histologic examination confirmed olfactory neuroblastoma.