tbuckley/cabot-search huggingface dataset:
Contributions of Depressive Mood and Circulating Inflammatory Markers to Coronary Heart Disease in Healthy European Men
Authors: J.P. Empana, D.H. Sykes, G. Luc, I. Juhan-Vague, D. Arveiler, J. Ferrieres, P. Amouyel, A. Bingham, M. Montaye, J.B. Ruidavets, B. Haas, A. Evans, X. Jouven, P. Ducimetiere
Journal: Circulation (2005)

Background— Data on the possible association between depressive disorders and inflammatory markers are scarce and inconsistent. We investigated whether subjects with depressive mood had higher levels of a wide range of inflammatory markers involved in coronary heart disease (CHD) incidence and examined the contribution of these inflammatory markers and depressive mood to CHD outcome. Methods and Results— We built a nested case-referent study within the Prospective Epidemiological Study of Myocardial Infarction (PRIME) study of healthy middle-aged men from Belfast and France. We considered the baseline plasma sample from 335 future cases (angina pectoris, nonfatal myocardial infarction, coronary death) and 670 matched controls (2 controls per case). Depressive mood characterized men whose baseline depression score (13-item modification of the Welsh depression subscale) was in the fourth quartile (mean score, 5.75; range, 4 to 12). On average, men with depressive mood had 46%, 16%, and 10% higher C-reactive protein, interleukin-6, and intercellular adhesion molecule-1 levels, respectively, independently of case-control status, social characteristics, and classic cardiovascular risk factors; no statistical difference was found for fibrinogen. The odds ratios of depressive mood for CHD were 1.35 (95% CI, 1.05 to 1.73) in univariate analysis and 1.50 (95% CI, 1.04 to 2.15) after adjustment for social characteristics and classic cardiovascular risk factors. The latter odds ratio remained unchanged when each inflammatory marker was added separately, and in this analysis, each inflammatory marker contributed significantly to CHD event risk. Conclusions— These data support an association of depressive mood with inflammatory markers and suggest that depressive mood is related to CHD even after adjustment for these inflammatory markers.
Gene-gene and gene-environment interactions: new insights into the prevention, detection and management of coronary artery disease
Authors: Matthew B Lanktree, Robert A Hegele
Journal: Genome Medicine (2009)

Despite the recent success of genome-wide association studies (GWASs) in identifying loci consistently associated with coronary artery disease (CAD), a large proportion of the genetic components of CAD and its metabolic risk factors, including plasma lipids, type 2 diabetes and body mass index, remain unattributed. Gene-gene and gene-environment interactions might produce a meaningful improvement in quantification of the genetic determinants of CAD. Testing for gene-gene and gene-environment interactions is thus a new frontier for large-scale GWASs of CAD. There are several anecdotal examples of monogenic susceptibility to CAD in which the phenotype was worsened by an adverse environment. In addition, small-scale candidate gene association studies with functional hypotheses have identified gene-environment interactions. For future evaluation of gene-gene and gene-environment interactions to achieve the same success as the single gene associations reported in recent GWASs, it will be important to pre-specify agreed standards of study design and statistical power, environmental exposure measurement, phenomic characterization and analytical strategies. Here we discuss these issues, particularly in relation to the investigation and potential clinical utility of gene-gene and gene-environment interactions in CAD.
Genetic Cardiomyopathies Causing Heart Failure
Authors: Thomas J. Cahill, Houman Ashrafian, Hugh Watkins
Journal: Circulation Research (2013)

Despite the striking advances in medical and surgical therapy, the morbidity, mortality, and economic burden of heart failure (HF) remain unacceptably high. There is increasing evidence that the risk and course of HF depend on genetic predisposition; however, the genetic contribution to HF is heterogeneous and complex. At one end of the spectrum are the familial monogenic HF syndromes in which causative mutations are rare but highly penetrant. At the other, HF susceptibility and course may be influenced by more common, less penetrant genetic variants. As detailed in this review, efforts to unravel the basis of the familial cardiomyopathies at the mendelian end of the spectrum already have begun to deliver on the promise of informative mechanisms, novel gene-based diagnostics, and therapies for distinct subtypes of HF. However, continued progress requires the differentiation of pathogenic mutations, disease modifiers, and rare, benign variants in the deluge of data emerging from increasingly accessible novel sequencing technologies. This represents a significant challenge and demands a sustained effort in analysis of extended family pedigrees, diligent clinical phenotyping, and systematic annotation of human genetic variation.
Counting alleles to predict recurrence of early-stage colorectal cancers
Authors: Wei Zhou, Steven N Goodman, Gennaro Galizia, Eva Lieto, Francesca Ferraraccio, Carlo Pignatelli, Colin A Purdie, Juan Piris, Robert Morris, David J Harrison, Philip B Paty, Al Culliford, Katharine E Romans, Elizabeth A Montgomery, Michael A Choti, Kenneth W Kinzler, Bert Vogelstein
Journal: The Lancet (2002)
Risk of Heart Failure in Breast Cancer Patients After Anthracycline and Trastuzumab Treatment: A Retrospective Cohort Study
Authors: E. J. A. Bowles, R. Wellman, H. S. Feigelson, A. A. Onitilo, A. N. Freedman, T. Delate, L. A. Allen, L. Nekhlyudov, K. A. B. Goddard, R. L. Davis, L. A. Habel, M. U. Yood, C. Mccarty, D. J. Magid, E. H. Wagner, None Pharmacovigilance Study Team
Journal: JNCI Journal of the National Cancer Institute (2012)

BackgroundClinical trials demonstrated that women treated for breast cancer with anthracycline or trastuzumab are at increased risk for heart failure and/or cardiomyopathy (HF/CM), but the generalizability of these findings is unknown. We estimated real-world adjuvant anthracycline and trastuzumab use and their associations with incident HF/CM.
Inquiry will study claims that Sellafield workers' body parts were removed without families' consent
Authors: Owen Dyer
Journal: BMJ (2007)

An independent inquiry will look into claims that body parts were removed from deceased workers at Sellafield nuclear power plant in Cumbria without their families' consent.

Michael Redfern QC, the barrister who led the inquiry into the retention of children's organs at Liverpool's Alder Hey Hospital, will examine what procedures were followed, whether consent was obtained, and what use was made of the tissues, said Alistair Darling, the trade and industry secretary, last week.

Sixty five cases in which tissue was taken from …
MEK Inhibition Leads to PI3K/AKT Activation by Relieving a Negative Feedback on ERBB Receptors
Authors: Alexa B. Turke, Youngchul Song, Carlotta Costa, Rebecca Cook, Carlos L. Arteaga, John M. Asara, Jeffrey A. Engelman
Journal: Cancer Research (2012)

Abstract The phosphoinositide 3-kinase (PI3K)/AKT and RAF/MEK/ERK signaling pathways are activated in a wide range of human cancers. In many cases, concomitant inhibition of both pathways is necessary to block proliferation and induce cell death and tumor shrinkage. Several feedback systems have been described in which inhibition of one intracellular pathway leads to activation of a parallel signaling pathway, thereby decreasing the effectiveness of single-agent targeted therapies. In this study, we describe a feedback mechanism in which MEK inhibition leads to activation of PI3K/AKT signaling in EGFR and HER2-driven cancers. We found that MEK inhibitor–induced activation of PI3K/AKT resulted from hyperactivation of ERBB3 as a result of the loss of an inhibitory threonine phosphorylation in the conserved juxtamembrane domains of EGFR and HER2. Mutation of this amino acid led to increased ERBB receptor activation and upregulation of the ERBB3/PI3K/AKT signaling pathway, which was no longer responsive to MEK inhibition. Taken together, these results elucidate an important, dominant feedback network regulating central oncogenic pathways in human cancer. Cancer Res; 72(13); 3228–37. ©2012 AACR.
Efforts to Diversify the Academic Pediatric Workforce
Authors: Darcy A. Thompson, Lee M. Pachter, David Keller
Journal: JAMA Pediatrics (2014)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA Pediatrics HomeNew OnlineCurrent IssueFor Authors Podcast Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA Pediatrics journal
Introduction: ASCO-ESMO Consensus Statement on Quality Cancer Care
Authors: Sandra J. Horning, Håkan Mellstedt
Journal: Journal of Clinical Oncology (2006)

On behalf of the American Society of Clinical Oncology (ASCO) and the European Society for Medical Oncology (ESMO), we are pleased to present the ASCO-ESMO Consensus Statement on Quality Cancer Care. The statement reflects the collective efforts of an international working group composed of volunteers from both ASCO and ESMO and was chaired by Heinz Ludwig, MD, of Austria, a Past President of ESMO and a 2005-2006 member of the ASCO International Affairs committee, and Tony Mok, MD, of Hong Kong, also a 2005-2006 member of the ASCO International Affairs committee. In 2006, patients with cancer face vast global discrepancies regarding their access to healthcare services, high quality cancer care, innovative drugs, clinical trials, multidisciplinary care, pain management, palliative care, healthcare information, and access to medical records, as well as regarding respect for their dignity, privacy, confidentiality, and the quality of physician-patient relationships. These gaps in various regions of our planet result in suboptimal outcomes and care, and account for the premature or even unnecessary deaths of thousands of patients today. If every cancer patient was treated and cared for in accordance with the best standards, much suffering and dying could be prevented. Both ASCO and ESMO are aware of inequalities in cancer care, consider them unacceptable, and strive to improve the situation of millions of patients with cancer. Hence, the societies have jointly drafted a statement that defines what we presently consider to be important to protect the interests of patients with cancer and to enable them to obtain high quality cancer care. We hope that this Consensus Statement will set the standard for the essential components of quality cancer care for policy makers, physicians, nurses, and other healthcare personnel. If widely applied, the Consensus Statement should not only improve patients’ autonomy and the quality of their cancer care, but most importantly, it will also prevent unnecessary suffering and save millions of lives. If supported by the many thousands of members of ASCO and ESMO, the Consensus Statement on Quality Cancer Care will become an eminently important global initiative.
The transplant iron score as a predictor of stem cell transplant survival
Authors: Jonathan A Storey, Rebecca F Connor, Zachary T Lewis, David Hurd, Gregory Pomper, Yi K Keung, Manisha Grover, James Lovato, Suzy V Torti, Frank M Torti, István Molnár
Journal: Journal of Hematology & Oncology (2009)

Abstract Recent studies have suggested that the presence of iron overload prior to stem cell transplantation is associated with decreased survival. Within these studies, the criteria used to define iron overload have varied considerably. Given the lack of consensus regarding the definition of iron overload in the transplant setting, we sought to methodically examine iron status among transplant patients. We studied 78 consecutive patients at risk for transfusion-related iron overload (diagnoses included AML, ALL, MDS, and aplastic anemia) who received either autologous or allogeneic stem cell transplant. Multiple measures of iron status were collected prior to transplantation and examined for their association with survival. Using this data, three potentially prognostic iron measures were identified and incorporated into a rational and unified scoring system. The resulting Transplant Iron Score assigns a point for each of the following variables: (1) greater than 25 red cell units transfused prior to transplantation; (2) serum ferritin &gt; 1000 ng/ml; and (3) a semi-quantitative bone marrow iron stain of 6+. In our cohort, the score (range 0 to 3) was more closely associated with survival than any available single iron parameter. In multivariate analysis, we observed an independent effect of iron overload on transplant survival (p = 0.01) primarily attributable to an increase in early treatment-related deaths (p = 0.02) and lethal infections. In subgroup analysis, the predictive power of the iron score was most pronounced among allogeneic transplant patients, where a high score (≥ 2) was associated with a 50% absolute decrease in survival at one year. In summary, our results lend further credence to the notion that iron overload prior to transplant is detrimental and suggest iron overload may predispose to a higher rate of lethal infections.
Factors predicting change in interpretation in PFTs when using FVC vs. the largest measured vital capacity
Authors: Denitza Blagev, Justin Dickerson, Olinto Linares-Perdomo, Dean Sorenson, Alan Morris
Journal: European Respiratory Journal (2014)

Background  Although ERS/ATS guidelines recommend using the largest measured vital capacity, VCmax, the FVC is commonly used in PFT interpretations. 6% of PFTs in a large database of all comers have a change in PFT interpretation based on which vital capacity is used in the interpretation.  Objective  To determine which factors predict increased likelihood of an interpretive change when FVC or VCmax are used.  Methods  12,238 PFTs obtained as part of routine clinical care were interpreted using both FVC and VCmax and 6% (710) of interpretations were changed. We examined all variables using a logistic regression model reporting adjusted odds ratios. The model satisfying our diagnostic criteria, generating the highest c-statistic, and achieving the most parsimonious solution was used to determine which variables increased the odds of recategorization.  Results  Compared to no bronchodilator test, bronchodilator test with a positive response increased the odds of recategorization to 18 (CI 13-24), and even a lack of a bronchodilator response increased the odds of recategorization to 7 (CI 5-9). Larger FVCs decreased the odds of recategorization (0.68, CI 0.63-0.74). The number of tests performed did not increase the odds of recategorization.  Conclusion  Bronchodilator testing and a positive bronchodilator response were the most likely to recategorize interpretations based on VCmax.
An unusual case of ankle arthropathy
Authors: S Abraham
Journal: Annals of the Rheumatic Diseases (2004)

A 65 year old white woman presented with a 5 year history of pain and intermittent swelling of the left ankle. There had been no preceding trauma to the ankle and the symptoms were initially gradual in onset with aching and stiffness but then evolved into a continuous pain, particularly nocturnally. Her previous medical history included a right total hip replacement aged 53, menopause aged 53, and essential hypertension. There was no family history of rheumatological illness and her mother died of a myocardial infarction aged 56 years.

Examination disclosed evidence of osteoarthritis in her hands and an unusual symmetrical bony swelling of her 1st and 2nd metacarpophalangeal joints. Her left ankle was swollen and warm to the touch (fig 1).



 Figure 1  
Left ankle demonstrating a palpable bony swelling.



Investigations disclosed …
The Central Governor Model in 2012: eight new papers deepen our understanding of the regulation of human exercise performance
Authors: Timothy D Noakes
Journal: British Journal of Sports Medicine (2011)

<h3>Abstract</h3> <h3>Motivation</h3> With an increasing number of patient-derived xenograft (PDX) models being created and subsequently sequenced to study tumor heterogeneity and to guide therapy decisions, there is a similarly increasing need for methods to separate reads originating from the graft (human) tumor and reads originating from the host species’ (mouse) surrounding tissue. Two kinds of methods are in use: On the one hand, alignment-based tools require that reads are mapped and aligned (by an external mapper/aligner) to the host and graft genomes separately first; the tool itself then processes the resulting alignments and quality metrics (typically BAM files) to assign each read or read pair. On the other hand, alignment-free tools work directly on the raw read data (typically FASTQ files). Recent studies compare different approaches and tools, with varying results. <h3>Results</h3> We show that alignment-free methods for xenograft sorting are superior concerning CPU time usage and equivalent in accuracy. We improve upon the state of the art sorting by presenting a fast lightweight approach based on three-way bucketed quotiented Cuckoo hashing. Our hash table requires memory comparable to an FM index typically used for read alignment and less than other alignment-free approaches. It allows extremely fast lookups and uses less CPU time than other alignment-free methods and alignment-based methods at similar accuracy. <h3>Availability</h3> Our software <i>xengsort</i> is available under the MIT license at http://gitlab.com/genomeinformatics/xengsort. It is written in numba-compiled Python and comes with Snakemake workflows for hash table construction and dataset processing. <h3>Contact</h3> Sven.Rahmann@uni-due.de
Cell cycle-dependent expression of Kv3.4 channels modulates proliferation of human uterine artery smooth muscle cells
Authors: Eduardo Miguel-Velado, Francisco D. Pérez-Carretero, Olaia Colinas, Pilar Cidad, Magda Heras, José R. López-López, M. Teresa Pérez-García
Journal: Cardiovascular Research (2010)

Vascular smooth muscle cell (VSMC) proliferation is involved in cardiovascular pathologies associated with unwanted arterial wall remodelling. Coordinated changes in the expression of several K+ channels have been found to be important elements in the phenotypic switch of VSMCs towards proliferation. We have previously demonstrated the association of functional expression of Kv3.4 channels with proliferation of human uterine VSMCs. Here, we sought to gain deeper insight on the relationship between Kv3.4 channels and cell cycle progression in this preparation. Expression and function of Kv3.4 channels along the cell cycle was explored in uterine VSMCs synchronized at different checkpoints, combining real-time PCR, western blotting, and electrophysiological techniques. Flow cytometry, Ki67 expression and BrdU incorporation techniques allowed us to explore the effects of Kv3.4 channels blockade on cell cycle distribution. We found cyclic changes in Kv3.4 and MiRP2 mRNA and protein expression along the cell cycle. Functional studies showed that Kv3.4 current amplitude and Kv3.4 channels contribution to cell excitability increased in proliferating cells. Finally, both Kv3.4 blockers and Kv3.4 knockdown with siRNA reduced the proportion of proliferating VSMCs. Our data indicate that Kv3.4 channels exert a permissive role in the cell cycle progression of proliferating uterine VSMCs, as their blockade induces cell cycle arrest after G2/M phase completion. The modulation of resting membrane potential (VM) by Kv3.4 channels in proliferating VSMCs suggests that their role in cell cycle progression could be at least in part mediated by their contribution to the hyperpolarizing signal needed to progress through the G1 phase.
How infants begin to extract words from speech
Authors: Peter W. Jusczyk
Journal: Trends in Cognitive Sciences (1999)

A crucial step for acquiring a native language vocabulary is the ability to segment words from fluent speech. English-learning infants first display some ability to segment words at about 7.5 months of age. However, their initial attempts at segmenting words only approximate those of fluent speakers of the language. In particular, 7.5-month-old infants are able to segment words that conform to the predominant stress pattern of English words. The ability to segment words with other stress patterns appears to require the use of other sources of information about word boundaries. By 10.5 months, English learners display sensitivity to additional cues to word boundaries such as statistical regularities, allophonic cues and phonotactic patterns. Infants' word segmentation abilities undergo further development during their second year when they begin to link sound patterns with particular meanings. By 24 months, the speed and accuracy with which infants recognize words in fluent speech is similar to that of native adult listeners. This review describes how infants use multiple sources of information to locate word boundaries in fluent speech, thereby laying the foundations for language understanding.
The adaptor molecules LAT and SLP-76 are specifically targeted by <i>Yersinia</i> to inhibit T cell activation
Authors: Christiane Gerke, Stanley Falkow, Yueh-hsiu Chien
Journal: The Journal of Experimental Medicine (2005)

T cell responses are critical to the survival of Yersinia-infected animals. Yersinia have the ability to directly suppress T lymphocyte activation through the virulence factor YopH, a tyrosine phosphatase. Using single cell video microscopy and FACS analysis, here we show that even an average of one Yersinia per T cell is sufficient to inhibit or alter T cell responses. This efficient inhibition is traced to specific targeting by YopH of the adaptor proteins, linker for activation of T cells (LAT) and SH2-domain-containing leukocyte protein of 76 kD (SLP-76), which are crucial for T cell antigen receptor (TCR) signaling. A catalytically inactive YopH translocated via the type III secretory pathway from the bacteria into T cells primarily binds to LAT and SLP-76. Furthermore, among the proteins of the TCR signaling pathway, the tyrosine phosphorylation levels of LAT and SLP-76 are the most affected in T cells exposed to low numbers of Yersinia pseudotuberculosis. This is the first example showing that a pathogen targets these adaptor proteins in the TCR signaling pathway, suggesting a novel mechanism by which pathogens may efficiently alter T cell-mediated immune responses.
Prospective comparison of recipient-site preparation with fractional carbon dioxide laser vs. dermabrasion and recipient-site dressing composition in melanocyte-keratinocyte transplantation procedure in vitiligo: a preliminary study
Authors: N. Silpa-archa, J.L. Griffith, M.S. Williams, H.W. Lim, I.H. Hamzavi
Journal: British Journal of Dermatology (2015)