tbuckley/cabot-search huggingface dataset:
Controversies in Radiation for Upper Rectal Cancers
Authors: Emily Chan, Paul E. Wise, A. Bapsi Chakravarthy
Journal: Journal of the National Comprehensive Cancer Network (2012)

Over the past few decades substantial improvement has occurred in the diagnosis and treatment of rectal cancers. This disease requires the close cooperation of a multidisciplinary team, including radiologists, gastroenterologists, surgeons, medical oncologists, and radiation oncologists, to provide optimum treatment with minimal morbidity. The widespread use of total mesorectal excision (TME) and improvements in chemotherapy and radiation delivery have resulted in decreases in locoregional recurrence. Large randomized studies have shown a benefit with the use of preoperative chemoradiation for most patients with transmural and/or node-positive disease. Controversy remains, however, regarding whether this treatment paradigm should be applied uniformly to all patients regardless of tumor location. As the risk of local recurrence decreases with high rectal tumors and the benefit in terms of sphincter preservation is not applicable to this subgroup of patients, up-front surgery to allow for more accurate pathologic staging prior to making final treatment decisions is recommended. In patients with pathologically staged T3,N0,M0 tumors of the upper rectum who have undergone TME with 12 or more nodes removed, the addition of chemoradiation has very little benefit.
Fibrolamellar hepatocellular carcinoma versus conventional hepatocellular carcinoma: better 5-year survival or artifactual result of research methodology?
Authors: Basile Njei
Journal: Gut (2013)

Among the primary hepatic malignant tumours, hepatocellular carcinoma (HCC) is the most common, while fibrolamellar carcinoma is a rare variant of HCC. In a recent article by Eggert et al examining the epidemiology of fibrolamellar hepatocellular carcinoma (fHCC) in the USA from 2000 to 2010,1 the authors reported better 5-year survival for fHCC compared with conventional HCC similar to previous studies.2–⇓⇓⇓⇓7 Even though several previous studies have advocated that fHCC is less aggressive than conventional HCC, some recent studies have failed to confirm the observation of a better outcome in fHCC.8–⇓⇓11 Cirrhosis is a well …
What is newsworthy? Longitudinal study of the reporting of medical research in two British newspapers
Authors: C. Bartlett
Journal: BMJ (2002)

<h3>Abstract</h3> <b>Objective:</b> To assess the characteristics of medical research that is press released by general medical journals and reported in newspapers. <b>Design:</b> Longitudinal study. <b>Data sources:</b> All original research articles published in <i>Lancet</i> and <i>BMJ</i> during 1999 and 2000. <b>Main outcome measures:</b> Inclusion of articles in <i>Lancet</i> or <i>BMJ</i> press releases, and reporting of articles in <i>Times</i> or <i>Sun</i> newspapers. <b>Results:</b> Of 1193 original research articles, 517 (43%) were highlighted in a press release and 81 (7%) were reported in one or both newspapers. All articles covered in newspapers had been press released. The probability of inclusion in press releases was similar for observational studies and randomised controlled trials, but trials were less likely to be covered in the newspapers (odds ratio 0.15 (95% confidence interval 0.06 to 0.37)). Good news and bad news were equally likely to be press released, but bad news was more likely to be reported in newspapers (1.74 (1.07 to 2.83)). Studies of women9s health, reproduction, and cancer were more likely to be press released and covered in newspapers. Studies from industrialised countries other than Britain were less likely to be reported in newspapers (0.51 (0.31 to 0.82)), and no studies from developing countries were covered. <b>Conclusions:</b> Characteristics of articles were more strongly associated with selection for reporting in newspapers than with selection for inclusion in press releases, although each stage influenced the reporting process. Newspapers underreported randomised trials, emphasised bad news from observational studies, and ignored research from developing countries. <h3>What is already known on this topic</h3> Newspapers are an important source of information about the results of medical research There are two stages on the path to newspaper coverage—selection by medical journal editors of articles to be press released and the selection of newsworthy articles by journalists <h3>What this study adds</h3> Examination of press releasing by the <i>Lancet</i> and <i>BMJ</i> and reporting by the <i>Times</i> and <i>Sun</i> showed that selection processes acted at both stages The net effect meant that newspapers emphasised results from observational studies, in particular studies of women9s health, reproduction, and cancer Good news and bad news were equally likely to be press released, but bad news was more likely to be reported in newspaper articles
Genome-wide association identifies multiple ulcerative colitis susceptibility loci
Authors: Dermot P B McGovern, Agnès Gardet, Leif Törkvist, Philippe Goyette, Jonah Essers, Kent D Taylor, Benjamin M Neale, Rick T H Ong, Caroline Lagacé, Chun Li, Todd Green, Christine R Stevens, Claudine Beauchamp, Phillip R Fleshner, Marie Carlson, Mauro D'Amato, Jonas Halfvarson, Martin L Hibberd, Mikael Lördal, Leonid Padyukov, Angelo Andriulli, Elisabetta Colombo, Anna Latiano, Orazio Palmieri, Edmond-Jean Bernard, Colette Deslandres, Daan W Hommes, Dirk J de Jong, Pieter C Stokkers, Rinse K Weersma, Yashoda Sharma, Mark S Silverberg, Judy H Cho, Jing Wu, Kathryn Roeder, Steven R Brant, L Phillip Schumm, Richard H Duerr, Marla C Dubinsky, Nicole L Glazer, Talin Haritunians, Andy Ippoliti, Gil Y Melmed, David S Siscovick, Eric A Vasiliauskas, Stephan R Targan, Vito Annese, Cisca Wijmenga, Sven Pettersson, Jerome I Rotter, Ramnik J Xavier, Mark J Daly, John D Rioux, Mark Seielstad
Journal: Nature Genetics (2010)
Prevalence of penicillin and erythromycin resistance among invasive Streptococcus pneumoniae isolates reported by laboratories in the southern and eastern Mediterranean region
Authors: M.A. Borg, E. Tiemersma, E. Scicluna, N. van de Sande-Bruinsma, M. de Kraker, J. Monen, H. Grundmann
Journal: Clinical Microbiology and Infection (2009)
Loss of the Ciliary Kinase Nek8 Causes Left-Right Asymmetry Defects
Authors: Danielle K. Manning, Mikhail Sergeev, Roy G. van Heesbeen, Michael D. Wong, Jin-Hee Oh, Yan Liu, R. Mark Henkelman, Iain Drummond, Jagesh V. Shah, David R. Beier
Journal: Journal of the American Society of Nephrology (2012)

A missense mutation in mouse Nek8, which encodes a ciliary kinase, produces the juvenile cystic kidneys (jck) model of polycystic kidney disease, but the functions of Nek8 are incompletely understood. Here, we generated a Nek8-null allele and found that homozygous mutant mice die at birth and exhibit randomization of left-right asymmetry, cardiac anomalies, and glomerular kidney cysts. The requirement for Nek8 in left-right patterning is conserved, as knockdown of the zebrafish ortholog caused randomized heart looping. Ciliogenesis was intact in Nek8-deficient embryos and cells, but we observed misexpression of left-sided marker genes early in development, suggesting that nodal ciliary signaling was perturbed. We also generated jck/Nek8 compound heterozygotes; these mutants developed less severe cystic disease than jck homozygotes and provided genetic evidence that the jck allele may encode a gain-of-function protein. Notably, NEK8 and polycystin-2 (PC2) proteins interact, and we found that Nek8(-/-) and Pkd2(-/-) embryonic phenotypes are strikingly similar. Nek8-deficient embryos and cells did express PC2 normally, which localized properly to the cilia. However, similar to cells lacking PC2, NEK8-depleted inner medullary collecting duct cells exhibited a defective response to fluid shear, suggesting that NEK8 may play a role in mediating PC2-dependent signaling.
Incidence of inflammatory bowel disease in Scottish children between 1968 and 1983; marginal fall in ulcerative colitis, three-fold rise in Crohn's disease.
Authors: J R Barton, S Gillon, A Ferguson
Journal: Gut (1989)

Linked hospital admission data for 1968-1983 were used to identify 723 children aged 16 years or less at the time of first admission to any Scottish hospital with an ICD coded diagnosis of Crohn9s disease (282) or ulcerative colitis (441). The accuracy of the coded diagnoses was checked by examination of the hospital notes of 144 patients. The coded diagnosis was incorrect in 11/83 coded as Crohn9s disease and 13/61 as ulcerative colitis; frequency of incorrect coding did not change significantly with time. Despite an 18% fall in the population aged less than or equal to 16 during this time, the number of new cases of Crohn9s disease rose from 10 in 1968 to 28 in 1983. Thus the recorded incidence of Crohn9s disease in Scottish children has risen more than three-fold in 16 years, from 6.6 to 22.9 per million (p less than 0.0001), with no difference between the sexes. Parallel data for ulcerative colitis were rendered inaccurate by miscoding of infective gastroenteritis as colitis. In an attempt to reduce this source of error cases aged five years and under were excluded from analysis, resulting in an incidence of 19.1 cases per million aged six to 16 in 1968 and 15.6 in 1983, not a significant change (r = 0.42, p = 0.052). When males and females were analysed separately, however, there was a significant decrease in the incidence of UC in male children (r = -0.4, p = 0.028), with no change for female children (r = 0.1, p = 0.595).
The New Medical Schools and Curriculum Innovation
Authors: Edwin F. Rosinki
Journal: JAMA (1971)

When the federal government made its commitment to support medical school construction and education almost nine years ago, many educators looked toward the schools that would be created as places where educational innovation would be accepted as a way of life. As of July 1970, a total of 11 of these new medical schools had become operational, ie, they admitted their first class of students. Yet the question remains: How innovative have these schools been? Few data are available but a review of schools' curricula is discouraging. "Innovative," "exciting," "progressive," "relevant," and "meaningful" are words used to describe the curriculum and courses of study. It would appear that the new schools are truly centers of innovation in education. But to anyone familiar with medical education, the curricula of these schools look like either the traditional basic-clinical science approach taught by discipline, or a variation of the curriculum pioneered by Case
Update in the understanding of altitude-induced limitations to performance in team-sport athletes
Authors: François Billaut, Robert J Aughey
Journal: British Journal of Sports Medicine (2013)

The internationalism of field-based team sports (TS) such as football and rugby requires teams to compete in tournaments held at low to moderate altitude (∼1200-2500 m). In TS, acceleration, speed and aerobic endurance are physical characteristics associated with ball possession and, ultimately, scoring. While these qualities are affected by the development of neuromuscular fatigue at sea level, arterial hypoxaemia induced by exposure to altitude may further hinder the capacity to perform consecutive accelerations (CAC) or sprint endurance and thereby change the outcome of a match. The higher the altitude, the more severe the hypoxaemia, and thus, the larger the expected decline in aerobic endurance, CAC and match running performance. Therefore, it is critical for athletes and coaches to understand how arterial hypoxaemia affects aerobic endurance and CAC and the magnitude of decline they may face at altitude for optimal preparation and increased chances of success. This mini review summarises the effects of acute altitude/hypoxia exposure on aerobic endurance, CAC and activity profiles of TS athletes performing in the laboratory and during matches at natural altitude, and analyses the latest findings about the consequences of arterial hypoxaemia on the relationship between peripheral perturbations, neural adjustments and performance during repeated sprints or CAC. Finally, we briefly discuss how altitude training can potentially help athletes prepare for competition at altitude.
Coupling of Fcγ Receptor I to Fcγ Receptor IIB by Src Kinase Mediates C-Reactive Protein Impairment of Endothelial Function
Authors: Nathan C. Sundgren, Weifei Zhu, Ivan S. Yuhanna, Ken L. Chambliss, Mohamed Ahmed, Keiji Tanigaki, Michihisa Umetani, Chieko Mineo, Philip W. Shaul
Journal: Circulation Research (2011)

Elevations in C-reactive protein (CRP) are associated with increased cardiovascular disease risk and endothelial dysfunction. CRP antagonizes endothelial nitric oxide synthase (eNOS) through processes mediated by the IgG receptor Fcγ receptor IIB (FcγRIIB), its immunoreceptor tyrosine-based inhibitory motif, and SH2 domain-containing inositol 5'-phosphatase 1. In mice, CRP actions on eNOS blunt carotid artery re-endothelialization.How CRP activates FcγRIIB in endothelium is not known. We determined the role of Fcγ receptor I (FcγRI) and the basis for coupling of FcγRI to FcγRIIB in endothelium.In cultured endothelial cells, FcγRI-blocking antibodies prevented CRP antagonism of eNOS, and CRP activated Src via FcγRI. CRP-induced increases in FcγRIIB immunoreceptor tyrosine-based inhibitory motif phosphorylation and SH2 domain-containing inositol 5'-phosphatase 1 activation were Src-dependent, and Src inhibition prevented eNOS antagonism by CRP. Similar processes mediated eNOS antagonism by aggregated IgG used to mimic immune complex. Carotid artery re-endothelialization was evaluated in offspring from crosses of CRP transgenic mice (TG-CRP) with either mice lacking the γ subunit of FcγRI (FcRγ(-/-)) or FcγRIIB(-/-) mice. Whereas re-endothelialization was impaired in TG-CRP vs wild-type, it was normal in both FcRγ(-/-); TG-CRP and FcγRIIB(-/-); TG-CRP mice.CRP antagonism of eNOS is mediated by the coupling of FcγRI to FcγRIIB by Src kinase and resulting activation of SH2 domain-containing inositol 5'-phosphatase 1, and consistent with this mechanism, both FcγRI and FcγRIIB are required for CRP to blunt endothelial repair in vivo. Similar mechanisms underlie eNOS antagonism by immune complex. FcγRI and FcγRIIB may be novel therapeutic targets for preventing endothelial dysfunction in inflammatory or immune complex-mediated conditions.
hSETD1A Regulates Wnt Target Genes and Controls Tumor Growth of Colorectal Cancer Cells
Authors: Tal Salz, Guangyao Li, Frederic Kaye, Lei Zhou, Yi Qiu, Suming Huang
Journal: Cancer Research (2013)

Abstract hSETD1A is a member of the trithorax (TrxG) family of histone methyltransferases (HMT) that methylate H3K4 at promoters of active genes. Although misregulation of mixed lineage leukemia (MLL) family proteins has been associated with acute leukemia, the role of hSETD1A in cancer remains unknown. In this study, we report that hSETD1A and its associated H3K4me3 are upregulated in human colorectal cancer cells and patient samples. Depletion of hSETD1A inhibits colorectal cancer cell growth, colony formation, and tumor engraftment. Genome-wide expression profiling of colorectal cancer cells reveals that approximately 50% of Wnt/β-catenin target genes are affected by the hSETD1A knockdown. We further demonstrate that hSETD1A is recruited to promoters of those Wnt signaling target genes through its interaction with β-catenin, a master regulator of the Wnt signaling pathway. The recruitment of the hSETD1A HMT complex confers promoter-associated H3K4me3 that leads to assembly of transcription preinitiation complex and transcriptional activation. Furthermore, the expression levels of hSETD1A are positively correlated with H3K4me3 enrichment at the promoters of Wnt/β-catenin target genes and the aberrant activation of these genes in human colorectal cancer. These results provide new biologic and mechanistic insights into the cooperative role of hSETD1A and β-catenin in regulation of Wnt target genes as well as in colorectal cancer cell growth in vitro and in vivo. Cancer Res; 74(3); 775–86. ©2013 AACR.
Reed-Elsevier, academics and the arms trade
Authors: D. N. Gill
Journal: Journal of the Royal Society of Medicine (2007)

In the letter we call on Reed to cease all involvement in arms fairs.In particular we state that Reed's involvement in the arms trade 'is entirely at odds with the ethical and social obligations we have to promote the beneficial applications of our work and prevent its misuse, to anticipate and evaluate the possible unintended consequences of scientific and technological developments, and to consider at all times the moral responsibility we carry for our work.'
Pacing-Induced Heart Failure in Dogs Enhances the Expression of p53 and p53-Dependent Genes in Ventricular Myocytes
Authors: Annarosa Leri, Yu Liu, Ashwani Malhotra, Qiong Li, Peter Stiegler, Pier Paolo Claudio, Antonio Giordano, Jan Kajstura, Thomas H. Hintze, Piero Anversa
Journal: Circulation (1998)

Background —Rapid ventricular pacing in dogs is characterized by a dilated myopathy in which myocyte cell death by apoptosis may play a significant role in the impairment of cardiac pump function. However, the molecular mechanisms implicated in the modulation of programmed cell death under this setting remain to be identified. Moreover, questions have been raised on the specificity and sensitivity of the histochemical detection of DNA strand breaks in nuclei by the terminal deoxynucleotidyl transferase (TdT) reaction. Methods and Results —Changes in the expression of Bcl -2 and Bax and their transcriptional regulator, p53, were determined by Western blot analysis in myocytes isolated from dogs affected by pacing-induced heart failure. A mobility shift assay for p53 binding activity was also performed. In addition, apoptosis was measured by confocal microscopy, which allowed the simultaneous detection of chromatin alterations and DNA damage. p53 DNA binding activity to the bax promoter was increased in nuclear extracts from myocytes obtained from failing hearts, and this response was associated with enhanced expression of Bax protein, 52%, and attenuation of Bcl -2, −92%. Immunolabeling of p53 in myocyte nuclei, measured by confocal microscopy, was 100% higher in cells from paced hearts. The combination of the TdT assay and confocal microscopy demonstrated that 20 myocyte nuclei per 10 6 were undergoing apoptosis in control myocardium and 4000 per 10 6 after pacing. Moreover, DNA laddering was shown in myocytes by agarose gel electrophoresis of DNA fragments. Conclusions —The activation of p53 and p53-dependent genes may be critical in the modulation of myocyte apoptosis in pacing-induced heart failure.
Valproic acid‐induced hepatotoxicity in alpers syndrome is associated with mitochondrial permeability transition pore opening‐dependent apoptotic sensitivity in an induced pluripotent stem cell model
Authors: Shengbiao Li, Jingyi Guo, Zhongfu Ying, Shen Chen, Liang Yang, Keshi Chen, Qi Long, Dajiang Qin, Duanqing Pei, Xingguo Liu
Journal: Hepatology (2015)

Valproic acid (VPA) is widely used to treat epilepsy, migraine, chronic headache, bipolar disorder, and as adjuvant chemotherapy, but potentially causes idiosyncratic liver injury. Alpers‐Huttenlocher syndrome (AHS), a neurometabolic disorder caused by mutations in mitochondrial DNA polymerase gamma (POLG), is associated with an increased risk of developing fatal VPA hepatotoxicity. However, the mechanistic link of this clinical mystery remains unknown. Here, fibroblasts from 2 AHS patients were reprogrammed to induced pluripotent stem cells (iPSCs) and then differentiated to hepatocyte‐like cells (AHS iPSCs‐Hep). Both AHS iPSCs‐Hep are more sensitive to VPA‐induced mitochondrial‐dependent apoptosis than controls, showing more activated caspase‐9 and cytochrome c release. Strikingly, levels of both soluble and oligomeric optic atrophy 1, which together keep cristae junctions tight, are reduced in AHS iPSCs‐Hep. Furthermore, POLG mutation cells show reduced POLG expression, mitochondrial DNA (mtDNA) amount, mitochondrial adenosine triphosphate production, as well as abnormal mitochondrial ultrastructure after differentiation to hepatocyte‐like cells. Superoxide flashes, spontaneous bursts of superoxide generation, caused by opening of the mitochondrial permeability transition pore (mPTP), occur more frequently in AHS iPSCs‐Hep. Moreover, the mPTP inhibitor, cyclosporine A, rescues VPA‐induced apoptotic sensitivity in AHS iPSCs‐Hep. This result suggests that targeting mPTP opening could be an effective method to prevent hepatotoxicity by VPA in AHS patients. In addition, carnitine or N ‐acetylcysteine, which has been used in the treatment of VPA‐induced hepatotoxicity, is able to rescue VPA‐induced apoptotic sensitivity in AHS iPSCs‐Hep. Conclusion : AHS iPSCs‐Hep are more sensitive to the VPA‐induced mitochondrial‐dependent apoptotic pathway, and this effect is mediated by mPTP opening. Toxicity models in genetic diseases using iPSCs enable the evaluation of drugs for therapeutic targets. (H epatology 2015;61:1730‐1739)
No impact of serum uric acid on the outcome of recent-onset arthritis
Authors: Anna Luczak, Rachel Knevel, T W J Huizinga, Jessica A B van Nies, Annette van der Helm-van Mil, Jeska Kirsten De Vries-Bouwstra
Journal: Annals of the Rheumatic Diseases (2012)

Patients with rheumatoid arthritis (RA) have an almost twofold increase of cardiovascular (CV) mortality and morbidity as compared with the general population and it is thought that chronic inflammation contributes to this association.1 Serum uric acid (SUA) can contribute to low-grade inflammation via increased production of C reactive protein (CRP) and influences cytokine and superoxide production by circulating neutrophils.2 ,3 In RA, higher levels of SUA have been associated with a higher prevalence of CV disease.4 At the joint level, monosodium urate crystals can negatively influence local bone remodelling by excessive osteoclast formation and reduced osteoblast differentiation.5, …
<i>De novo</i> Induction of Genetically Engineered Brain Tumors in Mice Using Plasmid DNA
Authors: Stephen M. Wiesner, Stacy A. Decker, Jon D. Larson, Katya Ericson, Colleen Forster, Jose L. Gallardo, Chunmei Long, Zachary L. Demorest, Edward A. Zamora, Walter C. Low, Karen SantaCruz, David A. Largaespada, John R. Ohlfest
Journal: Cancer Research (2009)

Abstract Spontaneous mouse models of cancer show promise to more accurately recapitulate human disease and predict clinical efficacy. Transgenic mice or viral vectors have been required to generate spontaneous models of glioma, a lethal brain tumor, because nonviral gene transfer is typically transient. To overcome this constraint, we used the Sleeping Beauty transposable element to achieve chromosomal integration of human oncogenes into endogenous brain cells of immunocompetent mice. Genetically engineered, spontaneous brain tumors were induced with plasmid DNA in a matter of weeks in three separate mouse strains. The phenotype of tumors was influenced by the combination of oncogenes delivered, resembling human astrocytoma or glioblastoma in the majority of cases. At least five different genes can be cotransfected simultaneously including reporters, allowing measurement of tumor viability by in vivo imaging. This model can accelerate brain tumor research in a variety of ways such as generation of “humanized” models for high throughput drug screening and candidate gene validation with exceptional speed and flexibility. [Cancer Res 2009;69(2):431–9]