tbuckley/cabot-search huggingface dataset:
From evidence cart to smart phone
Authors: Kamran Abbasi
Journal: Journal of the Royal Society of Medicine (2016)

Where do you stand on Brexit? You might find this a hard question since facts are difficult to establish. Sober analysis is lost amid the feverish passions of protagonists. The effects on health and science may not be top priorities for politicians, but they should be important considerations. In an attempt to cut through the red rage of emotion, clinicians and scientists from Imperial College explain why a vote for Brexit is a mistake.1

I expect many readers will disagree with our editorialists, and even if they do agree with them their vote will be won or lost for other reasons. Whatever the outcome of the referendum on 23 June, the challenges to UK’s health services remain stark. In the dash for health service reform, new care models, and the promised land of innovation, the value of evidence needs to be reinforced.

Like other innovations, those designed to improve evidence-informed practice are difficult to implement and evaluate. The world famous ‘evidence cart’ pioneered at Oxford’s John Radcliffe Hospital in the 1990s was an attempt to bring the library to the bedside. While the cart helped improve decision-making based on searches of evidence resources, its bulk and reliance on power cables made it an impractical companion on wards rounds and emergency departments. Smart phones have made these issues irrelevant, but the challenge remains of integrating relevant evidence with clinical data to promote optimal patient care.2

Marshall et al.3 argue that the ‘know-do’ gap in health services research may be greater than in clinical research. Many service changes are implemented, they say, unguided by research evidence. Walk-in centres, integrated care programmes and independent sector treatment centres are just three examples of service changes ‘that have gone badly awry’. In an age where Barnsley Football Club has a poet in residence and the All England Tennis Club employs an artist in residence, a researcher in residence on a clinical team might be the catalyst to achieving participatory research that brings about successful service transformation?

Whether in or out of Europe, you might want to consider the main finding of this month’s research paper, which finds no support for low, aspirational, BMIs among adult patients on hospital discharge.4 Whether you prefer your evidence best delivered by cart, smart phone or researcher in residence, research evidence has the power to surprise and challenge received wisdom.
MUFFINN: cancer gene discovery via network analysis of somatic mutation data
Authors: Ara Cho, Jung Eun Shim, Eiru Kim, Fran Supek, Ben Lehner, Insuk Lee
Journal: Genome biology (2016)

A major challenge for distinguishing cancer-causing driver mutations from inconsequential passenger mutations is the long-tail of infrequently mutated genes in cancer genomes. Here, we present and evaluate a method for prioritizing cancer genes accounting not only for mutations in individual genes but also in their neighbors in functional networks, MUFFINN (MUtations For Functional Impact on Network Neighbors). This pathway-centric method shows high sensitivity compared with gene-centric analyses of mutation data. Notably, only a marginal decrease in performance is observed when using 10 % of TCGA patient samples, suggesting the method may potentiate cancer genome projects with small patient populations.
Phosphodiesterase Type 5 Inhibitors and Risk of Malignant Melanoma: Matched Cohort Study Using Primary Care Data from the UK Clinical Practice Research Datalink
Authors: Anthony Matthews, Sinéad M. Langan, Ian J. Douglas, Liam Smeeth, Krishnan Bhaskaran
Journal: PLoS Medicine (2016)

Background Laboratory evidence suggests that reduced phosphodiesterase type 5 (PDE5) expression increases the invasiveness of melanoma cells; hence, pharmacological inhibition of PDE5 could affect melanoma risk. Two major epidemiological studies have investigated this and come to differing conclusions. We therefore aimed to investigate whether PDE5 inhibitor use is associated with an increased risk of malignant melanoma, and whether any increase in risk is likely to represent a causal relationship. Methods and Findings We conducted a matched cohort study using primary care data from the UK Clinical Practice Research Datalink. All men initiating a PDE5 inhibitor and with no prior cancer diagnosis were identified and matched on age, diabetes status, and general practice to up to four unexposed controls. Ever use of a PDE5 inhibitor and time-updated cumulative number of PDE5 inhibitor prescriptions were investigated as exposures, and the primary outcome was malignant melanoma. Basal cell carcinoma, solar keratosis, and colorectal cancer were investigated as negative control outcomes to exclude bias. Hazard ratios (HRs) were estimated from Cox models stratified by matched set and adjusted for potential confounders. 145,104 men with ≥1 PDE5 inhibitor prescription, and 560,933 unexposed matched controls were included. In total, 1,315 incident malignant melanoma diagnoses were observed during 3.44 million person-years of follow-up (mean 4.9 y per person). After adjusting for potential confounders, there was weak evidence of a small positive association between PDE5 inhibitor use and melanoma risk (HR = 1.14, 95% CI 1.01–1.29, p = 0.04). A similar increase in risk was seen for the two negative control outcomes related to sun exposure (HR = 1.15, 95% CI 1.11–1.19, p < 0.001, for basal cell carcinoma; HR = 1.21, 95% CI 1.17–1.25, p < 0.001, for solar keratosis), but there was no increased risk for colorectal cancer (HR = 0.91, 95% CI 0.85–0.98, p = 0.01). There was no evidence that risk increased with number of prescriptions received (p-trend = 0.83). In a post hoc analysis, there was strong evidence that solar keratosis was associated with future PDE5 inhibitor use (odds ratio = 1.28, 95% CI 1.23–1.34, p < 0.001), suggesting that men with higher sun exposure were more likely to become PDE5 inhibitor users. However, a limitation of our study was that we did not have individual-level data on sun exposure, so we could not directly control for this in the primary analysis. Conclusions Our results were not consistent with PDE5 inhibitors being causally associated with melanoma risk, and strongly suggest that observed risk increases are driven by greater sun exposure among patients exposed to a PDE5 inhibitor.
Studies on Tumor Antigens&lt;xref ref-type="fn" rid="FN1"&gt;2&lt;/xref&gt;
Authors: Zilber, L. A.
Journal: JNCI Journal of the National Cancer Institute (1957)

Journal Article Studies on Tumor Antigens Get access L. A. Zilber L. A. Zilber Member of the Academy of Medical Sciences of the U. S. S. R. Department of Immunology and Oncology, N. F. Gamaleya Institute of Epidemiology and Microbiology, Moscow, U. S. S. R. Search for other works by this author on: Oxford Academic PubMed Google Scholar JNCI: Journal of the National Cancer Institute, Volume 18, Issue 3, March 1957, Pages 341–358, https://doi.org/10.1093/jnci/18.3.341 Published: 01 March 1957 Article history Received: 27 July 1956 Published: 01 March 1957
ACRODERMATITIS ENTEROPATHICA
Authors: Ian Sneddon
Journal: British Journal of Dermatology (1974)

Journal Article ACRODERMATITIS ENTEROPATHICA Get access Ian Sneddon Ian Sneddon Rupert Hallam Department of Dermatology, Sheffield Search for other works by this author on: Oxford Academic Google Scholar British Journal of Dermatology, Volume 91, Issue 6, 1 December 1974, Page 716, https://doi.org/10.1111/j.1365-2133.1974.tb12465.x Published: 01 December 1974
Cardiopulmonary resuscitation
Authors: J Castillo Monsegur
Journal: JAMA (1986)

<h3>To the Editor.—</h3> The June 6,1986, issue of<i>JAMA</i>contains much valuable information in "Standards and Guidelines for Cardiopulmonary Resuscitation (CPR) and Emergency Cardiac Care (ECC)."<sup>1</sup>However, there is an error on page 2941 regarding the dosage of sodium nitroprusside. While the solution is commonly prepared by adding 50 mg to 250 to 1000 mL of dextrose in water as stated, the dose is usually 0.5 to 10 μg/kg/min, with an average of 3 μg/kg/min. We believe it is important to call it to the attention of readers as early as possible to avoid the effects of the larger dose of milligrams.
Letter to the editor: Application of Bayesian methods to the inference of phylogeny for enterovirus surveillance
Authors: J A Roberts, A Hung, B R Thorley
Journal: Eurosurveillance (2013)

Preview this article: Letter to the editor: Application of Bayesian methods to the inference of phylogeny for enterovirus surveillance, Page 1 of 1 < Previous page | Next page > /docserver/preview/fulltext/eurosurveillance/18/9/art20409-en-1.gif
Leukoedema and Keratosis in Relation to Leukoplakia of the Buccal Mucosa in Man
Authors: Harold R. Sandstead, Jere W. Lowe
Journal: JNCI Journal of the National Cancer Institute (1953)

Journal Article Leukoedema and Keratosis in Relation to Leukoplakia of the Buccal Mucosa in Man Get access Harold R. Sandstead, Harold R. Sandstead Search for other works by this author on: Oxford Academic PubMed Google Scholar Jere W. Lowe Jere W. Lowe Search for other works by this author on: Oxford Academic PubMed Google Scholar JNCI: Journal of the National Cancer Institute, Volume 14, Issue 2, October 1953, Pages 423–437, https://doi.org/10.1093/jnci/14.2.423 Published: 01 October 1953 Article history Received: 27 March 1953 Published: 01 October 1953
AT-15ATYPICAL TERATOID/RHABDOID TUMOURS: CYCLIN D1 OVEREXPRESSION AND MYC GENE EVALUATION IN A SERIES OF 56 CASES
Authors: Sridhar Epari, T.S. Nagaraj, Akash Sali, Girish Chinaswamy, Jayantsastri Goda, Prakash Shetty, Aliasagar Moiyadi, Tejpal Gupta, Rakesh Jalali
Journal: Neuro-Oncology (2016)
The Hearst trial and the confidentiality of residency records
Authors: L C Terr
Journal: American Journal of Psychiatry (1977)

Review of the Hearst trial transcript reveals that the subpoena Dr. Joel Fort's residency files met with very little effective resistance on the part of the hospital that had trained him. There are few legal mechanisms to stop such a subpoena. The only truly effective solution may be the abstraction and destruction of residency files once the residency has been successfully completed.
Muscular dystrophy in young girls.
Authors: B A Kakulas, P E Cullity, P Maguire
Journal: BMJ (1970)

Muscular dystrophy occurred in four girls. In only one of these was the syndrome both proximal and with pseudo-hypertrophy, thus clinically resembling the x-linked Duchenne type of the disease. The evidence for a primary dystrophic process existing in the four individuals is based on the laboratory findings of very high serum creatine kinase levels, myopathic E.M.G. appearances and muscle biopsies. However, each case is clinically different (one is proximal with contractures, another limb girdle with facial involvement and the fourth is distal) and worthy of documentation. The recent demonstration of a neurogenic basis for several myopathies previously considered to be dystrophic in nature has not caused us to revise our view that true muscular dystrophy does occur in girls but that the "Duchenne-like" type is rare.
Trends in drug consumption and risk of transmission of HIV and hepatitis C virus among injecting drug users in Switzerland, 1993-2006
Authors: F Dubois-Arber, H Balthasar, T Huissoud, F Zobel, S Arnaud, S Samitca, A Jeannin, D Schnoz, J P Gervasoni
Journal: Eurosurveillance (2008)

As a part of the HIV behavioural surveillance system in Switzerland, repeated cross-sectional surveys were conducted in 1993, 1994, 1996, 2000 and 2006 among attenders of all low threshold facilities (LTFs) with needle exchange programmes and/or supervised drug consumption rooms for injection or inhalation in Switzerland. Data were collected in each LTF over five consecutive days, using a questionnaire that was partly completed by an interviewer and partly self administered. The questionnaire was structured around three topics: socio-demographic characteristics, drug consumption, health and risk/preventive behaviour. Analysis was restricted to attenders who had injected drugs during their lifetime (IDUs). Between 1993 and 2006, the median age of IDUs rose by 10 years. IDUs are severely marginalised and their social situation has improved little. The borrowing of used injection equipment (syringe or needle already used by other person) in the last six months decreased (16.5% in 1993, 8.9% in 2006) but stayed stable at around 10% over the past three surveys. Other risk behaviour, such as sharing spoons, cotton or water, was reported more frequently, although also showed a decreasing trend. The reported prevalence of HIV remained fairly stable at around 10% between 1993 and 2006; reported levels of hepatitis C virus (HCV) prevalence were high (56.4% in 2006). In conclusion, the overall decrease in the practice of injection has reduced the potential for transmission of infections. However as HCV prevalence is high this is of particular concern, as the current behaviour of IDUs indicates a potential for further spreading of the infection. Another noteworthy trend is the significant decrease in condom use in the case of paid sex.
Targeting histone methylation for cancer therapy: enzymes, inhibitors, biological activity and perspectives
Authors: Yongcheng Song, Fangrui Wu, Jingyu Wu
Journal: Journal of Hematology & Oncology (2016)

Post-translational methylation of histone lysine or arginine residues plays important roles in gene regulation and other physiological processes. Aberrant histone methylation caused by a gene mutation, translocation, or overexpression can often lead to initiation of a disease such as cancer. Small molecule inhibitors of such histone modifying enzymes that correct the abnormal methylation could be used as novel therapeutics for these diseases, or as chemical probes for investigation of epigenetics. Discovery and development of histone methylation modulators are in an early stage and undergo a rapid expansion in the past few years. A number of highly potent and selective compounds have been reported, together with extensive preclinical studies of their biological activity. Several compounds have been in clinical trials for safety, pharmacokinetics, and efficacy, targeting several types of cancer. This review summarizes the biochemistry, structures, and biology of cancer-relevant histone methylation modifying enzymes, small molecule inhibitors and their preclinical and clinical antitumor activities. Perspectives for targeting histone methylation for cancer therapy are also discussed.
Acute Hepatic Failure Associated with the Use of Sodium Valproate
Authors: Frederick J. Suchy, William F. Balistreri, John J. Buchino, Judith M. Sondheimer, Stephen R. Bates, Gregory L. Kearns, John D. Stull, Kevin E. Bove
Journal: New England Journal of Medicine (1979)

SODIUM valproate, a recently introduced anticonvulsant, is particularly useful in the management of absence seizures and has gained widespread popularity.1 Initial European studies reported infrequ...
Abstract 1089: Dissecting the potential distinct role/s of the four RNA binding domains in a phosphoprotein nucleolin using bioinformatics tools
Authors: Ruchama Chaya Steinberg, Shaneen Singh, Anjana D. Saxena
Journal: Cancer Research (2015)

Abstract Nucleolin is an abundant RNA binding protein within the nucleolus containing four copies of a consensus RNA-binding domain (RBD1-4). Two of these contiguous RNA-binding domains (RBD12) are sufficient to bind to a variety of RNAs (e.g. rRNA, mRNA, ncRNA) through their highly conserved RNP-1/2 motifs. Nucleolin controls gene expression either post-transcriptionally through mRNA stability or by post-translational regulation, targeting mRNAs with ARE (AU-rich elements), NRE (nucleolin recognition elements) and/or G-rich regions. Nucleolin's RNA binding functions are directly implicated in various pathological conditions e.g. Alzheimer's disease, cancer and viral infection. Interestingly, nucleolin RNA binding properties and phosphorylation pattern change during the cellular response to stress suggesting possible collaboration in regulating gene expression. However, most RNA binding properties of nucleolin studied to date exclude its highly acidic N-terminus phosphorylation domain. Importantly, NMR structures are only available for RBD12 although RBD1-4 of nucleolin is required to interact with the evolutionary conserved motif (ECM) on pre-RNAs, which have important role/s in RNA processing. Our work in accordance with others has shown that the N-terminus domain plays a vital role in cell proliferation and therefore has potential to influence RNA-binding properties of nucleolin to regulate gene expression. Here we use bioinformatics tools to elucidate the RNA binding functions of all four RBDs of nucleolin individually and in various combinations. Using I-TASSER, a tertiary structure prediction algorithm, and the available structural data for RBD12, we first predicted models for RBD3 and 4.These models displayed nearly perfect superimposition of RBD34 with RBD12 where RBD3/2 and RBD4/1 align. Our central hypothesis is that nucleolin RBD3/4 domains can replace RBD1/2 domains in binding to RNAs. To test our hypothesis we have generated a variety of theoretical constructs of RBD1-4 with mutations in the RNP1/2 conserved sites of individual RBDs. We present the computational analyses of these constructs to predict the role/s of RBD3/4. We further predict any role/s imparted by N-terminus phosphorylation and/or the C-terminus GAR (Gly-Arg rich) domains in regulating RNA binding by nucleolin. This bioinformatics-based knowledge will provide useful insights about nucleolin-RNA interactions that can be framed into rationally designed experiments. Citation Format: Ruchama Chaya Steinberg, Shaneen Singh, Anjana D. Saxena. Dissecting the potential distinct role/s of the four RNA binding domains in a phosphoprotein nucleolin using bioinformatics tools. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 1089. doi:10.1158/1538-7445.AM2015-1089
Blocking NF-κB Is Essential for the Immunotherapeutic Effect of Recombinant IL18 in Pancreatic Cancer
Authors: Xingjun Guo, Lei Zheng, Jianxin Jiang, Yan Zhao, Xin Wang, Ming Shen, Feng Zhu, Rui Tian, Chengjian Shi, Meng Xu, Xu Li, Feng Peng, Hang Zhang, Yechen Feng, Yu Xie, Xiaodong Xu, Wei Jia, Ruizhi He, Chencheng Xie, Jun Hu, Dawei Ye, Min Wang, Renyi Qin
Journal: Clinical Cancer Research (2016)

We sought to find new immune-based treatments for pancreatic cancer.We detected IL18 expression in plasma and specimens from patients with pancreatic cancer. We then investigated whether IL18 had a therapeutic effect for pancreatic cancer in vitro and in vivo and any underlying mechanisms.Higher plasma IL18 was associated with longer overall survival (OS), but higher IL18 in pancreatic cancer tissues was associated with shorter OS and increased invasion and metastasis. Recombinant IL18 alone had no antitumor effect in the syngeneic mice with orthotopically transplanted tumors and promoted tumors in immunocompromised mice; it also facilitated immune responses in vitro and in vivo by augmenting the activity of cytotoxic T cells and NK cells in peripheral blood and lymph nodes. However, IL18 promoted the proliferation and invasion of pancreatic cancer cells, in vitro and in vivo, through the NF-κB pathway. Nevertheless, by coadministrating IL18 with BAY11-7082, an NF-κB inhibitor, we were able to prevent the procancerous effects of IL18 and prolong the survival time of the mice.IL18 has both cancer-promoting and cancer-suppressing functions. Although its single-agent treatment has no therapeutic effect on pancreatic cancer, when combined with the NF-κB pathway inhibitor, IL18 improved survival in a murine pancreatic cancer model. Our study implies the possibility of a combinational immunotherapy that uses IL18 and targets NF-κB pathway. Clin Cancer Res; 22(23); 5939-50. ©2016 AACR.
Electrophysiological (H-reflex) studies of patients with tardive dyskinesia
Authors: J W Crayton, R C Smith, D Klass, S Chang, S E Ericksen
Journal: American Journal of Psychiatry (1977)

The authors studied the H-reflex recovery curves of 31 schizophrenic patients with tardive dyskinesia in response to acute administrations of apomorphine, amphetamine, or physostigmine and compared them with curves of chronic schizophrenic patients without tardive dyskinesia and normal volunteers. Their most unexpected finding was the absence of an H-reflex in 9 of the 31 patients with tardive dyskinesia. They also found a relationship between severity of tardive dyskinesia and the value of the facilitatory peak Hchi: patients with more severe tardive dyskinesia symptoms had significantly higher values for Hchi.
Primary Malignant Bone Tumors
Authors: George White, Milton Elkin
Journal: New England Journal of Medicine (1951)

NINETY-THREE cases of primary malignant bone tumor have been observed at the Pondville Hospital in the past twenty-one years. The group under consideration consists of: Ewing's tumor, osteogenic sarcoma, osteogenic sarcoma arising from Paget's disease, chondrosarcoma and periosteal fibrosarcoma. These cases correspond to other reported series in respect to age grouping, sex distribution, site of the primary tumor, presenting symptoms, metastases and longevity. Bone tumors usually manifest themselves early through pain and swelling; methods for definitive diagnosis are easily available; the tumor site is usually accessible for radical therapy. Yet in spite of these seemingly favorable circumstances, the over-all salvage . . .
Activation of liver X receptor/retinoid X receptor pathway ameliorates liver disease in Atp7B−/− (Wilson disease) mice
Authors: James P. Hamilton, Lahari Koganti, Abigael Muchenditsi, Venkata S. Pendyala, David Huso, Joseph Hankin, Robert C. Murphy, Dominik Huster, Uta Merle, Christopher Mangels, Nan Yang, James J. Potter, Esteban Mezey, Svetlana Lutsenko
Journal: Hepatology (2015)

Wilson disease (WD) is a hepatoneurological disorder caused by mutations in the copper-transporter, ATP7B. Copper accumulation in the liver is a hallmark of WD. Current therapy is based on copper chelation, which decreases the manifestations of liver disease, but often worsens neurological symptoms. We demonstrate that in Atp7b(-/-) mice, an animal model of WD, liver function can be significantly improved without copper chelation. Analysis of transcriptional and metabolic changes in samples from WD patients and Atp7b(-/-) mice identified dysregulation of nuclear receptors (NRs), especially the liver X receptor (LXR)/retinoid X receptor heterodimer, as an important event in WD pathogenesis. Treating Atp7b(-/-) mice with the LXR agonist, T0901317, ameliorated disease manifestations despite significant copper overload. Genetic markers of liver fibrosis and inflammatory cytokines were significantly decreased, lipid profiles normalized, and liver function and histology were improved.The results demonstrate the major role of an altered NR function in the pathogenesis of WD and suggest that modulation of NR activity should be explored as a supplementary approach to improving liver function in WD. (Hepatology 2016;63:1828-1841).