tbuckley/cabot-search huggingface dataset:
Kaiser Permanente's experience of implementing an electronic medical record: a qualitative study
Authors: J Tim Scott, Thomas G Rundall, Thomas M Vogt, John Hsu
Journal: BMJ (2005)

<h3>Abstract</h3> <b>Objective</b> To examine users9 attitudes to implementation of an electronic medical record system in Kaiser Permanente Hawaii. <b>Design</b> Qualitative study based on semistructured interviews. <b>Setting</b> Four primary healthcare teams in four clinics, and four specialty departments in one hospital, on Oahu, Hawaii. Shortly before the interviews, Kaiser Permanente stopped implementation of the initial system in favour of a competing one. <b>Participants</b> Twenty six senior clinicians, managers, and project team members. <b>Results</b> Seven key findings emerged: users perceived the decision to adopt the electronic medical record system as flawed; software design problems increased resistance; the system reduced doctors9 productivity, especially during initial implementation, which fuelled resistance; the system required clarification of clinical roles and responsibilities, which was traumatic for some individuals; a cooperative culture created trade-offs at varying points in the implementation; no single leadership style was optimal—a participatory, consensus-building style may lead to more effective adoption decisions, whereas decisive leadership could help resolve barriers and resistance during implementation; the process fostered a counter climate of conflict, which was resolved by withdrawal of the initial system. <b>Conclusions</b> Implementation involved several critical components, including perceptions of the system selection, early testing, adaptation of the system to the larger organisation, and adaptation of the organisation to the new electronic environment. Throughout, organisational factors such as leadership, culture, and professional ideals played complex roles, each facilitating and hindering implementation at various points. A transient climate of conflict was associated with adoption of the system.
Heart Rate Variability during Chronic Hemodialysis and after Renal Transplantation
Authors: DVORA RUBINGER, DAN SAPOZNIKOV, ARTHUR POLLAK, MORDECAI M. POPOVTZER, MYRON H. LURIA
Journal: Journal of the American Society of Nephrology (1999)

Abstract. The present study was undertaken to compare heart rate variability (HRV) values in patients on maintenance hemodialysis with no evidence of ischemic or hypertensive heart diseases to those of age- and gender-matched healthy individuals and those of patients after renal transplantation. To assess the effects of a common confounding factor, HRV values were also determined in patients with systemic amyloidosis, in chronic hemodialysis, and after successful renal transplantation. Spectral analyses of RR intervals from continuous electrocardiogram recordings were performed to quantify ultra low frequency, very low frequency, low frequency, and high frequency powers. HRV determinations were all significantly reduced in uremic patients undergoing hemodialysis compared with the healthy control subjects, especially in those with systemic amyloidosis. Renal transplantation normalized HRV in most patients; HRV, however, remained reduced in isolated amyloidosis patients with cardiac or adrenal involvement. HRV circadian day/night differences were preserved in hemodialysis patients and after renal transplantation in those without amyloidosis but not in those with amyloidosis. These data suggest that reduced HRV in chronic hemodialysis patients may precede other manifestations of cardiovascular disease. In uremic patients with amyloidosis, a more severe form of autonomic failure may occur. Successful transplantation corrects HRV abnormalities in most patients, suggesting that the autonomic dysfunction of uremia is caused by humoral factors reversed by the normalization of the renal function.
Purifying Selection and Birth-and-death Evolution in the Histone H4 Gene Family
Authors: Helen Piontkivska, Alejandro P. Rooney, Masatoshi Nei
Journal: Molecular Biology and Evolution (2002)

Histones are small basic proteins encoded by a multigene family and are responsible for the nucleosomal organization of chromatin in eukaryotes. Because of the high degree of protein sequence conservation, it is generally believed that histone genes are subject to concerted evolution. However, purifying selection can also generate a high degree of sequence homogeneity. In this study, we examined the long-term evolution of histone H4 genes to determine whether concerted evolution or purifying selection was the major factor for maintaining sequence homogeneity. We analyzed the proportion (p(S)) of synonymous nucleotide differences between the H4 genes from 59 species of fungi, plants, animals, and protists and found that p(S) is generally very high and often close to the saturation level (p(S) ranging from 0.3 to 0.6) even though protein sequences are virtually identical for all H4 genes. A small proportion of genes showed a low level of p(S) values, but this appeared to be caused by recent gene duplication. Our findings suggest that the members of this gene family evolve according to the birth-and-death model of evolution under strong purifying selection. Using histone-like genes in archaebacteria as outgroups, we also showed that H1, H2A, H2B, H3, and H4 histone genes in eukaryotes form separate clusters and that these classes of genes diverged nearly at the same time, before the eukaryotic kingdoms diverged.
A genome-wide approach to identify genetic loci with a signature of natural selection in the Irish population.
Authors: Valeria Mattiangeli, Anthony W Ryan, Ross McManus, Daniel G Bradley
Journal: Genome biology (2006)

Abstract Background In this study we present a single population test (Ewens-Waterson) applied in a genomic context to investigate the presence of recent positive selection in the Irish population. The Irish population is an interesting focus for the investigation of recent selection since several lines of evidence suggest that it may have a relatively undisturbed genetic heritage. Results We first identified outlier single nucleotide polymorphisms (SNPs), from previously published genome-wide data, with high F ST branch specification in a European-American population. Eight of these were chosen for further analysis. Evidence for selective history was assessed using the Ewens-Watterson's statistic calculated using Irish genotypes of microsatellites flanking the eight outlier SNPs. Evidence suggestive of selection was detected in three of these by comparison with a population-specific genome-wide empirical distribution of the Ewens-Watterson's statistic. Conclusion The cystic fibrosis gene, a disease that has a world maximum frequency in Ireland, was among the genes showing evidence of selection. In addition to the demonstrated utility in detecting a signature of natural selection, this approach has the particular advantage of speed. It also illustrates concordance between results drawn from alternative methods implemented in different populations.
Fasting-induced G0/G1 switch gene 2 and FGF21 expression in the liver are under regulation of adipose tissue derived fatty acids
Authors: Doris Jaeger, Gabriele Schoiswohl, Peter Hofer, Renate Schreiber, Martina Schweiger, Thomas O. Eichmann, Nina M. Pollak, Nadja Poecher, Gernot F. Grabner, Kathrin A. Zierler, Sandra Eder, Dagmar Kolb, Franz P.W. Radner, Karina Preiss-Landl, Achim Lass, Rudolf Zechner, Erin E. Kershaw, Guenter Haemmerle
Journal: Journal of Hepatology (2015)

<h3>Background & Aims</h3> Adipose tissue (AT)-derived fatty acids (FAs) are utilized for hepatic triacylglycerol (TG) generation upon fasting. However, their potential impact as signaling molecules is not established. Herein we examined the role of exogenous AT-derived FAs in the regulation of hepatic gene expression by investigating mice with a defect in AT-derived FA supply to the liver. <h3>Methods</h3> Plasma FA levels, tissue TG hydrolytic activities and lipid content were determined in mice lacking the lipase co-activator comparative gene identification-58 (CGI-58) selectively in AT (<i>CGI-58-</i>ATko) applying standard protocols. Hepatic expression of lipases, FA oxidative genes, transcription factors, ER stress markers, hormones and cytokines were determined by qRT-PCR, Western blotting and ELISA. <h3>Results</h3> Impaired AT-derived FA supply upon fasting of <i>CGI-58-</i>ATko mice causes a marked defect in liver PPARα-signaling and nuclear CREBH translocation. This severely reduced the expression of respective target genes such as the ATGL inhibitor G0/G1 switch gene-2 (G0S2) and the endocrine metabolic regulator FGF21. These changes could be reversed by lipid administration and raising plasma FA levels. Impaired AT-lipolysis failed to induce hepatic G0S2 expression in fasted <i>CGI-58-</i>ATko mice leading to enhanced ATGL-mediated TG-breakdown strongly reducing hepatic TG deposition. On high fat diet, impaired AT-lipolysis counteracts hepatic TG accumulation and liver stress linked to improved systemic insulin sensitivity. <h3>Conclusions</h3> AT-derived FAs are a critical regulator of hepatic fasting gene expression required for the induction of G0S2-expression in the liver to control hepatic TG-breakdown. Interfering with AT-lipolysis or hepatic G0S2 expression represents an effective strategy for the treatment of hepatic steatosis.
Stimulatory effects of induced phagocytosis on the function of isolated thyroid cells
Authors: K. Kowalski, D. Babiarz, S. Sato, G. Burke
Journal: Journal of Clinical Investigation (1972)

Stimulation of endocytosis is a very early effect of thyrotropin on thyroid. However, the relationship of the endocytotic process to the many other thyrotropin effects on thyroid is not clearly defined. Since phagocytosis in isolated thyroid cells is a presumed model for in vivo endocytosis of colloid, we induced phagocytosis in isolated thyroid cells by incubating them at 37 degrees C with 0.109-mu diameter polystyrene microbeads; phagocytosis was confirmed in each experiment by electron microscopy and/or spectrophotometric analysis of dioxane cell extracts. Cells incubated with 50-100-mu diameter polystyrene macrobeads (too large to ingest) served as controls. Microbead-induced phagocytosis in isolated thyroid cells was consistently accompanied by increases in: (a) cyclic 3',5'-adenosine monophosphate-(14)C formation from adenine-8-(14)C (66%); (b) iodide-(131)I trapping (40%); (c) protein and RNA synthesis (30%); (d) phospholipogenesis (50%); (e) alpha-aminoisobutyric acid-1-(14)C uptake (15%). 50- to 100-mu diameter polystyrene macrobeads did not influence cell function in any of these experiments. Aminotriazole, 5 x 10(-3) (M), a peroxidase inhibitor, blocked the stimulatory effect of microbead-induced phagocytosis on phospholipogenesis only. These studies indicate that in isolated thyroid cells the phagocytotic process, per se, may alter activity of the membrane-bound adenyl cyclase enzyme. The resultant increase in cyclic 3',5'-adenosine monophosphate may be a triggering mechanism for (some) subsequent metabolic changes occuring during phagocytosis. Since these changes mimic those induced by thyrotropin, it is suggested that a variety of thyrotropin effects on thyroid may be secondary to stimulation of colloid resorption and hormone secretion.
Non-invasive mapping of connections between human thalamus and cortex using diffusion imaging
Authors: T E J Behrens, H Johansen-Berg, M W Woolrich, S M Smith, C A M Wheeler-Kingshott, P A Boulby, G J Barker, E L Sillery, K Sheehan, O Ciccarelli, A J Thompson, J M Brady, P M Matthews
Journal: Nature Neuroscience (2003)
Gluteal muscle activity and patellofemoral pain syndrome: a systematic review
Authors: Christian J Barton, Simon Lack, Peter Malliaras, Dylan Morrissey
Journal: British Journal of Sports Medicine (2012)

Objective There is growing evidence to support the association of gluteal muscle strength deficits in individuals with patellofemoral pain syndrome (PFPS) and the effectiveness of gluteal strengthening when treating PFPS. In additiona, an impressive body of work evaluating gluteal electromyography (EMG) has recently emerged, further supporting the importance of gluteal muscle function in PFPS. This systematic review synthesises these EMG findings in order to better understand the role of gluteal muscle activity in the aetiology, presentation and management of PFPS. Methods MEDLINE, EMBASE, CINAHL, Web of Knowledge and Google Scholar databases were searched in September 2011 for prospective and case–control studies evaluating the association of gluteal EMG with PFPS. Two independent reviewers assessed each paper for inclusion and quality. Means and SDs were extracted from each included study to allow effect size calculations and comparison of results. Results Ten case–control, but no prospective studies were identified. Moderate-to-strong evidence indicates gluteus medius (GMed) activity is delayed and of shorter duration during stair negotiation in PFPS sufferers. In addition, limited evidence indicates GMed activity is delayed and of shorter duration during running, and gluteus maximus (GMax) activity is increased during stair descent. Conclusions Delayed and shorter duration of GMed EMG may indicate impaired ability to control frontal and transverse plane hip motion. Further research evaluating the value of gluteal muscle activity screening in identifying individuals most likely to develop PFPS, and the effectiveness of interventions targeting changes to gluteal muscle activation patterns is needed.
Big hits on the small screen: an evaluation of concussion-related videos on YouTube
Authors: David Williams, S John Sullivan, Anthony G Schneiders, Osman Hassan Ahmed, Hopin Lee, Arun Prasad Balasundaram, Paul R McCrory
Journal: British Journal of Sports Medicine (2013)

YouTube is one of the largest social networking websites, allowing users to upload and view video content that provides entertainment and conveys many messages, including those related to health conditions, such as concussion. However, little is known about the content of videos relating to concussion.To identify and classify the content of concussion-related videos available on YouTube.An observational study using content analysis.YouTube's video database was systematically searched using 10 search terms selected from MeSH and Google Adwords. The 100 videos with the largest view counts were chosen from the identified videos. These videos and their accompanying text were analysed for purpose, source and description of content by a panel of assessors who classified them into data-driven thematic categories.434 videos met the inclusion criteria and the 100 videos with the largest view counts were chosen. The most common categories of the videos were the depiction of a sporting injury (37%) and news reports (25%). News and media organisations were the predominant source (51%) of concussion-related videos on YouTube, with very few being uploaded by professional or academic organisations. The median number of views per video was 26 191.Although a wide range of concussion-related videos were identified, there is a need for healthcare and educational organisations to explore YouTube as a medium for the dissemination of quality-controlled information on sports concussion.
Site-Specific Structural Constraints on Protein Sequence Evolutionary Divergence: Local Packing Density versus Solvent Exposure
Authors: So-Wei Yeh, Jen-Wei Liu, Sung-Huan Yu, Chien-Hua Shih, Jenn-Kang Hwang, Julian Echave
Journal: Molecular Biology and Evolution (2013)

Protein sequences evolve under selection pressures imposed by functional and biophysical requirements, resulting in site-dependent rates of amino acid substitution. Relative solvent accessibility (RSA) and local packing density (LPD) have emerged as the best candidates to quantify structural constraint. Recent research assumes that RSA is the main determinant of sequence divergence. However, it is not yet clear which is the best predictor of substitution rates. To address this issue, we compared RSA and LPD with site-specific rates of evolution for a diverse data set of enzymes. In contrast with recent studies, we found that LPD measures correlate better than RSA with evolutionary rate. Moreover, the independent contribution of RSA is minor. Taking into account that LPD is related to backbone flexibility, we put forward the possibility that the rate of evolution of a site is determined by the ease with which the backbone deforms to accommodate mutations.
t-DARPP regulates phosphatidylinositol-3-kinase-dependent cell growth in breast cancer
Authors: Bhavatarini Vangamudi, Dun-Fa Peng, Qiuyin Cai, Wael El-Rifai, Wei Zheng, Abbes Belkhiri
Journal: Molecular Cancer (2010)

Abstract Background Recent reports have shown that t-DARPP (truncated isoform of DARPP-32) can mediate trastuzumab resistance in breast cancer cell models. In this study, we evaluated expression of t-DARPP in human primary breast tumors, and investigated the role of t-DARPP in regulating growth and proliferation in breast cancer cells. Results Quantitative real time RT-PCR analysis using primers specific for t-DARPP demonstrated overexpression of t-DARPP in 36% of breast cancers (13/36) as opposed to absent to very low t-DARPP expression in normal breast tissue (p &lt; 0.05). The mRNA overexpression of t-DARPP was overwhelmingly observed in ductal carcinomas, including invasive ductal carcinomas and intraductal carcinomas, rather than other types of breast cancers. The immunohistochemistry analysis of DARPP-32/t-DARPP protein(s) expression in breast cancer tissue microarray that contained 59 tumors and matched normal tissues when available indicated overexpression in 35.5% of primary breast tumors that were more frequent in invasive ductal carcinomas (43.7%; 21/48). In vitro studies showed that stable overexpression of t-DARPP in MCF-7 cells positively regulated proliferation and anchorage-dependent and -independent growth. Furthermore, this effect was concomitant with induction of phosphorylation of AKT ser473 and its downstream target phospho ser9 GSK3β, and increased Cyclin D1 and C-Myc protein levels. The knockdown of endogenous t-DARPP in HCC1569 cells led to a marked decrease in phosphorylation of AKTs ser473 and GSK3β ser9 . The use of PI3K inhibitor LY294002 or Akt siRNA abrogated the t-DARPP-mediated phosphorylation of AKT ser473 and led to a significant reduction in cell growth. Conclusions Our findings underscore the potential role of t-DARPP in regulating cell growth and proliferation through PI3 kinase-dependent mechanism.
<i>p53 Arg72Pro</i> Polymorphism, HPV Status and Initiation, Progression, and Development of Cervical Cancer: A Systematic Review and Meta-Analysis
Authors: Steven Habbous, Vincent Pang, Lawson Eng, Wei Xu, Goldie Kurtz, Fei-Fei Liu, Helen Mackay, Eitan Amir, Geoffrey Liu
Journal: Clinical Cancer Research (2012)

Cervical cancer develops through progression from normal cervical epithelium through squamous intraepithelial lesions (SIL) to invasive cancer. Cervical cancer is associated with oncogenic human papillomavirus (HPV). The HPV E6 oncoprotein binds to the tumor suppressor gene product p53, promoting its degradation; the Arg allele of p53 Arg72Pro polymorphism binds more ardently with HPV E6 than the Pro variant. Here we evaluate the role of p53 Arg72Pro polymorphism and HPV status on the initiation, progression, and development of cervical cancer. A systematic review and meta-analysis were conducted. Events of interest were the initiation of neoplasia (SIL vs. normal), progression to invasive cancer (cervical cancer vs. SIL), and risk of invasive cancer (cervical cancer vs. normal) by HPV status. OR were extracted from individual studies and pooled using generic inverse variance and random effects modeling. Forty-nine studies were included. In individuals showing HPV positivity, there was a significantly higher odds of progression from SIL to cervical cancer with the p53 Arg allele [OR 1.37; 95% confidence intervals (CI), 1.15-1.62; P < 0.001]. This association was not seen in HPV-negative individuals. p53 Arg72Pro was not associated with the risk of cervical cancer or initiation of SIL in either HPV-positive or HPV-negative patient subsets. The Arg variant of p53 Arg72Pro is associated with progression of SIL to cervical cancer only in the presence of HPV positivity. There were no associations of this variant with overall risk or initiation of cancer in either HPV-positive or HPV-negative patients. Clin Cancer Res; 18(23); 6407-15.
EXACERBATIONS OF CHRONIC BRONCHITIS TREATMENT WITH OXYTETRACYCLINE
Authors: D.G. Berry, John Fry, C.P. Hindley, J.M. Hodson, E.J. Horder, J.P. Horder, E.A.W. Marien, J.N. Rea, Anthony Ryle, M.P. Curwen, A.J.H. Tomlinson
Journal: The Lancet (1960)
Endophenotypes in the Genetic Analyses of Mental Disorders
Authors: Tyrone D. Cannon, Matthew C. Keller
Journal: Annual Review of Clinical Psychology (2005)

Common mental disorders such as schizophrenia, bipolar disorder, and severe major depression are highly heritable, but differ from single-gene (Mendelian) diseases in that they are the end products of multiple causes. Although this fact may help explain their prevalence from an evolutionary perspective, the complexity of the causes of these disorders makes identification of disease-promoting genes much more difficult. The "endophenotype" approach is an alternative method for measuring phenotypic variation that may facilitate the identification of susceptibility genes for complexly inherited traits. Here we examine the endophenotype construct in context of psychiatric genetics. We first develop an evolutionary theoretical framework for common mental disorders and differentiate them from simpler, single-gene disorders. We then provide a definition and description of endophenotypes, elucidating several features that will make a proposed endophenotype useful in psychiatric genetic research and evaluating the methods for detecting and validating such endophenotypes. We conclude with a review of recent results in the schizophrenia literature that illustrate the usefulness of endophenotypes in genetic analyses of mental disorders, and discuss implications of these findings for models of disease causation and nosology. Given that in mental disorders as in behavior generally, the pathways from genotypes to phenotypes are circuitous at best, discernment of endophenotypes more proximal to the effects of genetic variation will aid attempts to link genes to disorders.