tbuckley/cabot-search huggingface dataset:
CAROTID INFLAMMATION INDEPENDENTLY PREDICTS INCREASED ONE-YEAR CARDIOVASCULAR EVENT RATE
Authors: Georgios Benetos, Konstantinos Toutouzas, Maria Drakopoulou, Fotini Mitropoulou, Iosif Koutagiar, Charalampia Nikolaou, Nikolaos Barampoutis, Periklis Davlouros, Elias Siores, Dimitris Tousoulis
Journal: Journal of the American College of Cardiology (2016)
Oncologists Discuss Barriers To Providing Treatment
Authors: L. Schwab
Journal: JNCI Journal of the National Cancer Institute (1991)

Journal Article Oncologists Discuss Barriers To Providing Treatment Get access Linda Schwab Linda Schwab Search for other works by this author on: Oxford Academic PubMed Google Scholar JNCI: Journal of the National Cancer Institute, Volume 83, Issue 7, 3 April 1991, Pages 468–469, https://doi.org/10.1093/jnci/83.7.468 Published: 03 April 1991
Abstract 3023: Rapid methylation profiling of multiple genes at the same time using the methylation ligation-dependent macroarray (MLM)
Authors: Jean Benhattar, Isabelle Guilleret
Journal: Cancer Research (2011)

Abstract Background: Aberrant methylation of multiple promoter CpG islands is a common event in human cancers. Methylation profile of cancer-related genes has extraordinary potential in basic research as well as translational medicine. The aim of this study was to replace the tedious and inefficient bisulfite-based methods with a simple technology which could permit a rapid and robust analysis of large numbers of genes in large numbers of tumor samples simultaneously. Materials and methods: Genomic DNA was first sonicated, then couples of primers for each specific gene promoter were annealed to this DNA. In a one-step reaction, the CfoI methylation-sensitive enzyme digested unmethylated DNA, whereas the Taq ligase joined primers annealed to the methylated sequence. Tagged ligation products were amplified by PCR and finally hybridized to a nylon membrane macroarray. Methylation Ligation-dependent Macroarray (MLM) allows the establishment of DNA methylation profiles on many samples (up to 21) and on many gene promoters (up to 45) in a simple reaction in 2-3 days. To validate this novel method, we used it to detect aberrant methylation in 14 cell lines and in DNA samples of 40 patients with a colorectal cancer. Results: In tumor cell lines, among the 42 genes investigated 23.7 (11-32) were found methylated whereas only 9 have been observed methylated in a normal fibroblast cell line (BJ). In normal colorectal tissues, about 12/40 gene promoters were found methylated; in colorectal cancers 16 to 36 genes were methylated. Methylated gene promoters identified in colorectal cancers were ADAMTS18 (78%), APC (28%), CDKN2A (20%), DKK2 (50%), GPx3 (48%), Mal (72%), MLH1 (30%), NELL1 (72%), SFRP4 (35%), SFRP5 (52%) and WRN (20%): Conclusion: The MLM is a fast, non expensive and reliable technology that profiles the DNA methylation status of &amp;gt;40 promoter CpG islands in various human samples. This technology can be used in research for rapid methylation profiling of numerous samples and for identification of new epigenetic biomarkers, but also in clinic for rapid cancer diagnosis, for predictive response to cancer therapy and for distinction between progressive and non-progressive diseases. 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 3023. doi:10.1158/1538-7445.AM2011-3023
Abstract 3313: Novel roles of CCN6 in mesenchymal-epithelial transition (MET) and loss of stem cell properties of breast cancer cells
Authors: Wei Huang, Celina G. Kleer
Journal: Cancer Research (2012)

Abstract Background: Epithelial-mesenchymal transition (EMT) and its reverse process, mesenchymal-epithelial transition (MET), play key roles in regulating embryogenesis. Recent studies have shown that aberrant EMT activation contributes to cancer progression and metastasis. Links between EMT and the gain of stem cell properties have been suggested in physiological and pathological situations. CCN family protein 6 (CCN6/WISP3) is a novel tumor suppressor that regulates diverse cellular functions. Our previous studies have shown the blockade of CCN6 by short hairpin RNA triggers EMT program in benign breast epithelial cells, with decreased expression of epithelial marker E-cadherin and increased activation of corresponding transcriptional repressor, Zeb1 and Snail. Moreover, loss of CCN6 expression also endows benign breast epithelial cells with growth factor-independent properties, such as cell survival and anoikis resistance. However, little is known regarding the functions of CCN6 overexpression in breast cancer progression. Methods: We overexpressed CCN6 in breast cancer cell lines, MDA-MB-231 and SUM-159, which are aggressive, have mesenchymal-like features and low levels of endogenous CCN6. CCN6 provoked functions were studied in vitro by proliferation, motility and invasion assays. Aldehyde dehydrogenase (ALDH1) was used to identify and investigate CCN6 roles in human breast cancer stem cells. Results: We showed that overexpression of CCN6 inhibits cell proliferation, motility and invasion. Importantly, CCN6 overexpression in these cells led to phenotypic changes towards mesenchymal-epithelial transition (MET), characterized by loss of mesenchymal cell marker Vimentin and downregulation of transcriptional factor, Zeb1. CCN6 overexpression significantly reduced the stem cell population of MDA-MB-231 and SUM-159 breast cancer cells. Conclusions: Our data suggest a novel function of CCN6 in regulating MET and reducing the stem cell population of aggressive breast cancer cells. 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 3313. doi:1538-7445.AM2012-3313
Symposium on Tobacco Bridges Research Gaps
Authors: F. Donodeo
Journal: JNCI Journal of the National Cancer Institute (1996)

Newsexists.Clinic notes and radiotherapy summaries are expected to come online soon.The third module, for outcome analysis, will produce 60 or 70 standard reports on a variety of clinical and financial outcomes, as well as ad hoc reports.On the clinical side, the module can analyze individual physicians to see, for instance, how often their patients on 5-FU become dehydrated or how often they progress down a pathway arm toward second-line therapy as opposed to complete remission. Financial AnalysisOn the financial side, the outcome module can perform analyses such as MSK Disease Management Teams Cancer treatment under the new disease management program at Memorial Sloan-Kettering Cancer Center is being divided among 17 disease management teams: Bone Breast Central nervous system (brain) Colorectal Genitourinary (except prostate) Gynecological Head and neck
Abstract 2021: Mechanism of the coordinate regulation of liver cancer by nuclear receptor CAR and beta catenin
Authors: Bingning Dong, David Moore
Journal: Cancer Research (2011)

Abstract Aberrant activation of β-catenin is a critical contributor to many different cancers, including up to 34% of human hepatocellular carcinogenesis. Liver-specific activation of β-catenin is not sufficient to drive tumorigenesis in mice. However, nearly all of the tumors produced in the widely used diethylnitrosamine (DEN; carcinogen) plus phenobarbital (PB; promoter) mouse liver cancer model have activating mutations in β-catenin. The nuclear receptor CAR, a primary regulator of drug metabolism and detoxification, is the target of PB in the DEN-PB model, suggesting a synergistic functional interaction of these two transcription factors. Thus, we hypothesize that β-catenin and CAR synergistically induce liver tumorigenesis. We induced CAR and full β-catenin activation by TC treatment (CAR agonist) of liver specific-Cre/catnb lox/lox(ex3) mice (homozygous β-catenin activation by knockout of phosphorylation sites in exon3). Consistent with previous studies, activation of either CAR or β-catenin only induces mild hepatomegaly but not tumorigenesis in one month. However, the combined activation of both CAR and β-catenin causes uncontrolled liver growth (up to 25% liver/body weight ratio). Ki67 staining reveals significant hepatocyte proliferation in the double activation group, but not in any of the single activation groups. This indicates that CAR and β-catenin coordinately regulates liver growth. Uncontrolled liver growth leads to mouse death, which prevents us studying tumorigenesis. Accordingly, we also treated liver specific-Cre/catnb wt/lox(ex3) mice (heterozygous β-catenin activation) with TC. After 8 month, HCC were observed in 13 out of 15 experimental treated mice whereas no tumor was observed in the control mice (either TC treated catnb wt/lox(ex3) mice or CRE treated catnb wt/lox(ex3) mice, suggesting a cooperative and synergistic role of CAR and β-catenin in HCC formation. Bioinformatic gene array analysis shows that tumors generated in our mouse model share similar expression signature with human HCC carrying β-catenin mutation. Thus, the study on the mechanism of our mouse model will provide new therapeutic approaches in liver cancer and its prevention. 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 2021. doi:10.1158/1538-7445.AM2011-2021
Doing medicine
Authors: Trisha Greenhalgh
Journal: BMJ (2007)

The cuddly yellow doggie in the room that I use for my GP consultations comes in for a lot of attention. If I need to examine a child with earache, we first look in the doggie's ears with my little light. If the child has a sore bottom, the doggie usually hides under the couch roll because he is embarrassed, but then obediently comes out and allows me to look, ever so gently. He wags his tail to show it didn't hurt, and then I ask the child if I may examine him or her.

Sometimes it's easier for a child to say how the doggie would be feeling right now than how they are feeling themselves. The doggie is useful to hold if you are about to get an injection, and afterwards, he can sniff his way to where the Smarties jar is kept. And if you are middle aged and working your way through a complex narrative of sadness and struggle, absent mindedly stroking the doggie will help the words come out.

Although I have occasionally got through an evening surgery without my stethoscope, I doubt if I could do it without the doggie. Yet in six years at medical school, nobody explained to me how much easier my work as a doctor would be if I recognised the consultation for what it is: a piece of theatre. Like most people reading this article, I completed entire courses at undergraduate and postgraduate level in which both student and examiner were required to sign up to the misconception that the clinical consultation is an exercise in pure deductive logic.

Thirty years since failing an audition with Cambridge Footlights on the grounds that I had no dramatic talent, I was chuffed to the core when a medical student described my double act with the doggie as “awesome.” Recently plucked from the predictable environment of the lecture theatre and hospital ward, he had quickly discovered that his well thumbed textbook of evidence based general practice did not actually tell him what to do with the fuzzy and multidimensional reality of illness in the community. And the essence of medical skill—in both primary and secondary care—is knowing what to do.

The difference between “knowing medicine” and “doing medicine” is the difference between a logical deduction and an outcome that is relevant to the patient. It is also the reason why all first year medical students should be issued with a soft toy or comparable prop and encouraged to improvise creatively with it in at least 50% of their interactions with patients.
Phenylketonuria Due to a Deficiency of Dihydropteridine Reductase
Authors: Seymour Kaufman, Neil A. Holtzman, Sheldon Milstien, Ian J. Butler, Allan Krumholz
Journal: New England Journal of Medicine (1975)

The onset of neurologic symptoms in a child who had markedly elevated blood phenylalanine levels during the first two weeks of life and who was promptly treated with a low phenylalanine diet, with excellent control of serum phenylalanine levels, suggested that this child had an unusual form of phenylketonuria. In assays of the components of the phenylalanine hydroxylating system (open liver biopsy at 14 months), the activity of phenylalanine hydroxylase was 20 per cent of the average normal adult value. By contrast, no dihydropteridine reductase activity was detected in the patient's liver, brain or cultured skin fibroblasts. Since dihydropteridine reductase is also essential for the biosynthesis of dopamine, norepinephrine, and serotonin, disturbed neurotransmitter function may be responsible for the patient's neurologic deterioration. On the basis of these results, assay of reductase in cultured skin fibroblasts may be advisable in the initial diagnosis of phenylketonuria.
Abstract 1213: Clinicopathological significance of ALK alterations in colorectal carcinoma.
Authors: Zeenath Jehan, Sarita Esther Prabhakaran, Rong Bu, Nasser Al-Sanea, Alaa Abduljabbar, Luai Ashari, Samar Al-Homoud, Fouad Al Dayel, Shahab Uddin, Prashant Bavi, Khawla Sami Al-Kuraya
Journal: Cancer Research (2013)

Abstract ALK has been shown to be a putative oncogene in lung cancer and neuroblastoma that can be potentially targeted with selective inhibitors. Ongoing clinical trials using ALK inhibitors such as Crizotinib have shown promising results. ALK gene copy gain number in colorectal cancer (CRC) patients have been shown to be associated with tumors that have a more aggressive phenotype. We investigated the alterations in ALK gene by FISH analysis, immunohistochemistry and screened for ALK mutations by sequencing the ALK gene in 737 CRC. We screened for mutations in ALK by sequencing the tyrosine kinase domain that covers exons 20 -28. ALK alterations were correlated with tumor pathological features including TNM staging, MSI status, KRAS and BRAF mutations, as well as clinical outcome. Overall survival was analyzed using Kaplan Meyer plots. On FISH analysis in colorectal cancers, ALK amplifications were observed in 2.6%. Amplifications and gain with increase in gene copy number(4 to 6 copies) were seen in 3.4%. No translocations were seen in our study. There were no associations with nodal metastasis and other clinical or molecular parameters. However in Stage III &amp; IV, ALK amplification was associated with KRAS mutations. CRC subgroup with ALK amplifications showed a poor overall survival overall survival and ALK gene amplifications was an independent prognostic marker in multivariate Cox proportional Hazards model. IHC showed cytoplasmic overexpression in 14.7% CRCs and no associations with any clinical or molecular parameters. We are screening for ALK mutations in 100 CRC samples and results are awaited. The insights gained from our current study and future clinical trials are likely to directly benefit subgroups of CRC patients whose tumors are driven by ALK and will pave the way to more targeted approaches to cancer treatment. Citation Format: Zeenath Jehan, Sarita Esther Prabhakaran, Rong Bu, Nasser Al-Sanea, Alaa Abduljabbar, Luai Ashari, Samar Al-Homoud, Fouad Al Dayel, Shahab Uddin, Prashant Bavi, Khawla Sami Al-Kuraya. Clinicopathological significance of ALK alterations in colorectal carcinoma. [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 1213. doi:10.1158/1538-7445.AM2013-1213
INFLUENCE OF AORTIC REGURGITANT JET DIRECTIONS ON MITRAL VALVE APPARATUS IN CHRONIC AORTIC REGURGITATION: A REAL-TIME THREE-DIMENSIONAL TRANSESOPHAGEAL ECHOCARDIOGRAPHY STUDY
Authors: Kensuke Hirasawa, Masaki Izumo, Taro Sasaoka, Takashi Ashikaga, Suzuki Kengo, Tomoo Harada, Mitsuaki Isobe, Yoshihiro Akashi
Journal: Journal of the American College of Cardiology (2016)
M20 Finding the missing millions: case finding for COPD in people attending other long term condition clinics in primary care
Authors: DMG Halpin, S Holmes, J Calvert, D McInerney
Journal: Thorax (2013)

<h3></h3> Over 40% of people with COPD remain undiagnosed. Co-morbidities are common in people with COPD but COPD is also a comorbidity of other long term conditions. As SHA respiratory leads in the SW we used this fact to develop a pilot programme to case find people with COPD among patients attending other long term clinics in primary care. The project was developed by the Leads and partially supported by Astra Zeneca, Boehringer Ingelheim, Chiesi &amp; Novartis who provided support for additional health care professional time, but it was also adopted by Bristol CCG. Practices were asked to show all current or ex-smokers aged ≥ 35 attending a long term condition clinic who were not known to have COPD a Patient Information Sheet and ask them to complete a questionnaire designed to help identify people with COPD (1). Patients were also asked to perform microspirometry using an ASMA-1 device, their age, height, &amp; smoking status were recorded. If they scored highly on the questionnaire and had an FEV1 below the lower limit of normal (LLN), their MRC breathlessness and CAT scores were recorded and they were offered further assessment within the practice to confirm the diagnosis. Smokers were offered referral to cessation services. 573 patients (323 men) were seen in 11 practices between Sep 2012 &amp; May 2013. Mean age 64.6 (range 36–90). 265 had high questionnaire scores and 115 of these also had FEV1 less than LLN–20% of all patients seen. The mean FEV1 (%pred) in these patients was 58.6 (range 5.5–77.6). 86 had an FEV 50–80% predicted, 25 30–50% predicted. 44 had an MRC score of 0, 13 of 1, 44 of 2, 8 of 3 and 4 of 5. The mean CAT score was 13.4 (range 2–40). 44 (38%) were still smoking and 17 of these accepted referral to cessation services. 27 of the other 125 smokers assessed but not thought to have COPD also accepted referral. Case finding using this method in people already attending primary care clinics has a high yield (1 in 5) takes little time and deserves wider adoption. <h3>References</h3> <i>Respiration</i> 2006;73:285–95.
Congenital Syphilis Presenting in Infants after the Newborn Period
Authors: David H. Dorfman, Joy H. Glaser
Journal: New England Journal of Medicine (1990)

There has been a recent, dramatic increase in the incidence of congenital syphilis, particularly in urban areas. We describe seven infants seen during one year who were first given a diagnosis of congenital syphilis at 3 to 14 weeks of age, when symptoms developed. We reviewed these infants' charts in order to ascertain the reasons for the failure to diagnose syphilis at birth and to identify the signs and symptoms of congenital syphilis in this group of infants.At delivery, four of the infants and their mothers had negative qualitative rapid-plasma-reagin tests for syphilis. The other three mothers had been seronegative during the pregnancy and were therefore not tested at delivery; two of their infants were seronegative at birth, and one was not tested. When the infants became symptomatic between 3 and 14 weeks of age and were admitted to the hospital, all seven infants and the five mothers available for testing were found to be seropositive for syphilis. Four infants presented with a characteristic diffuse rash; the other three presented with fever and were found on admission to have aseptic meningitis. All these infants had multisystem disease, as evidenced by hepatomegaly, increased aminotransferase and alkaline phosphatase levels, anemia, and monocytosis. In all the infants syphilis responded to parenteral penicillin.Congenital syphilis may be missed if serologic tests are not performed for both the mother and her infant at the time of delivery. Even when these tests are performed, some infants are not identified as having syphilis, probably because the infection is very recent and there has been insufficient time for an antibody response to develop. Some infants with congenital syphilis of later onset do not present with a typical rash; therefore, at least in areas where the disease is prevalent, serologic tests for syphilis should be included in the evaluation of all febrile infants, even those with negative results on serologic testing at birth.
NEW GENERATION DRUG-ELUTING STENT SUPERIOR TO BENCHMARK XIENCE DRUG-ELUTING STENT
Authors: Masato Nakamura, Satoru Otsuji, Yoshihisa Nakagawa, Yuji Oikawa, Nobuo Shiode, Masatoshi Miyahara, Gaku Nakazawa, Hiroyoshi Yokoi
Journal: Journal of the American College of Cardiology (2016)
Clinical Significance of Rapid (Accelerated) Gastric Emptying
Authors: Amolak Singh, Humara Gull, Rubin J. Singh
Journal: Clinical Nuclear Medicine (2003)

The purpose of this study was to determine the significance and frequency of rapid gastric emptying (RGE) in clinical practice and to examine its relationship to age, gender, and presenting symptoms.The review included 750 patients who underwent scintigraphic gastric emptying studies (GES) within the past 11 years. In 80 patients with RGE, the mean gastric emptying time (GET) in female and male patients was compared with study gender differences. Similarly, the mean GET in young and old patients was compared with study age differences. The presenting symptoms and conditions indicating GES were noted.RGE was found in 80 of 750 study patients (10.7%). RGE was equally common in both sexes. Younger patients (mean age, 34.3 +/- 9.5 years) and older patients (mean age, 67.3 +/- 11.6 years) had similar mean GETs. Most patients with RGE presented with symptoms that mimicked gastroparesis.RGE has no relationship to age or gender. RGE may be representative of early dumping syndrome in most patients. GES help make a clear distinction between early dumping syndrome and gastroparesis, which can present with similar symptoms.