tbuckley/cabot-search huggingface dataset:
Abstract P5-09-07: Impact of germinalcenter-associated nuclear protein polymorphisms on breast cancer risk and prognosis in a Japanese population
Authors: H Kotani, H Ito, K Kuwahara, K Kuzushima, H Iwata, N Tsunoda, M Nagino, H Tanaka, K Matsuo
Journal: Cancer Research (2017)

Abstract Background: Germinal center-associated nuclear protein (GANP) is a phosphoprotein which is involved in mRNA export and the regulation of DNA recombination. We have previously demonstrated that deficiency of GANP led to spontaneous development of mammary gland tumors in a mouse model. In addition, we found that decreased GANP expression in human breast cancer tissue was an independent prognostic factor. Here, we conducted a case-control study and a retrospective cohort study to investigate whether single nucleotide polymorphisms (SNPs) of GANP are associated with sporadic breast cancer risk and prognosis in a Japanese population. Subjects and Methods: Six hundred-ninety-four breast cancer cases and 1,376 age- and menopausal status-matched controls were selected within the framework of the Hospital-based Epidemiologic Research Program at Aichi Cancer Center. Cases and controls were genotyped using an Infinium iSelect custom array (iCOGS, Illumina Inc., San Diego, CA, USA). We assessed 13 SNPs at the GANP locus, 2 SNPs (rs2839178 and rs11702450) were selected for further analysis by considering linkage disequilibrium. Conditional logistic regression methods were used to estimate odds ratios (ORs) and 95% confidence intervals. In addition, the survival impact of the two SNPs was retrospectively analyzed using the 694 breast cancer cases. To evaluate the effect of SNPs on overall survival (OS) and disease-free survival (DFS), multivariate Cox proportional hazards modeling was applied. Results: Compared to the AA genotype of rs2839178, the GG genotype showed statistically significant associations with breast cancer risk (OR: 0.48, 95%CI:0.30–0.76, P = 0.002). In prognostic analysis, compared to those with the genotype AA at rs2839178, patients with AG or GG showed longer DFS (HR: 0.71, 95%CI: 0.49–1.04 and 0.42, 0.13–1.42, respectively, P for trend = 0.04). The GG genotype of rs2839178 also showed a positive tendency for longer OS although it was not statistically significant (HR: 0.69, 95%CI: 0.44–1.08, P = 0.11). We did not find that rs11702450 was associated with either breast cancer risk or prognosis. Conclusion: This is the first study to investigate the association between GANP SNPs and breast cancer risk and prognosis. The direction of association with DFS was consistent with that of susceptibility. These results demonstrate that GANP SNPs presumably prevent the occurrence and malignant advancement of sporadic breast cancers. Citation Format: Kotani H, Ito H, Kuwahara K, Kuzushima K, Iwata H, Tsunoda N, Nagino M, Tanaka H, Matsuo K. Impact of germinalcenter-associated nuclear protein polymorphisms on breast cancer risk and prognosis in a Japanese population [abstract]. In: Proceedings of the 2016 San Antonio Breast Cancer Symposium; 2016 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2017;77(4 Suppl):Abstract nr P5-09-07.
Electronic Cigarette Use in US Households With Children
Authors: Jenny L. Carwile, Abby F. Fleisch, Kirsten Young, Katherine A. Ahrens
Journal: JAMA Pediatrics (2019)

The reliability (ICC) of the number of sit-to-stands was excellent, but a learning effect (t test) was observed (Table 2).The number of repetitions was greater in STST2 than in STST1 in 43 patients (83%).The repeatability of the number of sit-tostands was verified with a bias of 2.5 (95% CI, 1.5-3.5)and limits of agreement of -4.9% (lower) and 9.9% (upper).Discussion | To our knowledge, this study demonstrated for the first time the concurrent validity and reliability of the STST to quantify the HR response during submaximal exercise in healthy children.Indeed, the cardiorespiratory responses to the STST and the 6MWT were similar and associated in the sample of healthy children.This result means that the STST is a good alternative field test to the 6MWT to evaluate cardiorespiratory demand.The STST is interesting because its submaximal exercise is similar to the 6MWT, but it is less time-consuming while also requiring fewer resources and no long hallway.Moreover, the reliability of the cardiorespiratory response measured by the STST at a 1-week interval was verified.Although we cannot consider the STST as a surrogate for the 6MWT for measuring the functional exercise capacity in children because of the lack of association with the walked distance, the STST was reliable for the number of repetitions measurement.The associated learning effect observed for the number of sit-to-stands, which contrasted with the adult results, could be explained by the differences in intrinsic motivation 5 and time perception 6 between adults and children.The STST could be used complementarily with the maximum incremental cardiopulmonary exercise test or when that test cannot be performed.
Management of agitated patients
Authors: Jason Luty, Robin Touquet
Journal: BMJ (2010)

Two consultants discuss how to manage anxious and agitated patients Irritability is the tendency to display impatience, anger, or displeasure. Any agitated or ill person is likely to be irritable. People can become irritable and angry because they are harassed, apprehensive, lonely, and tired (HALT). For example, they may have had an argument with their partner, or have been kept waiting too long. Management of the irritable or agitated patient is not really about treatment of illness, but about the doctor-patient relationship. It is essential to know how to put someone at ease and establish a good rapport, and to know what to do if you become angry or upset when you encounter agitated patients. You also need to recognise when to clinically manage irritability and agitation. A good way to start when dealing with an irritable or agitated patient is to introduce yourself and say why you are there. Psychiatrists usually start a consultation with, “What problems have you been having lately?” or “How can I help you?” Box 1 gives some tips on how to put someone at ease. #### Box 1: Putting someone at ease
A new concept: “PSA clearance” predicts biochemical relapse risk of patients with prostate cancer in the first month following radical prostatectomy.
Authors: Benoit You, Paul Perrin, Gilles Freyer, Claire Falandry, Benjamin Ribba, Emilie Henin, Alain Ruffion, Philippe Paparel, Brigitte Tranchand, Olivier Tredan, Jean-Pierre Droz, Pascal Girard
Journal: Cancer Research (2008)

969  Purpose: Feasibility study for a new method to accurately assess PSA decrease in patients with prostate cancer after radical prostatectomy (PSA clearance (CLPSA)) and to identify relationships between PSA decrease profile and relapse free survival (RFS) . Indeed the current method used to describe PSA decrease after surgery (individual PSA half-life calculation, nadir) in patients with prostate tumors is source of biases and inaccuracies and may alter the prognostic value of PSA decline profile. We propose to apply the same population kinetic approach that is used in drug pharmacokinetic studies in order to estimate PSA clearance (CLPSA) which dynamically quantifies body PSA elimination.  Method: This was a retrospective study on 67 consecutive patients undergoing radical prostatectomy in the same center from November 2000 to December 2006. Fifty five patients had at least 3 PSA dosages in the first month after the procedure (total 162 PSA dosages). A population model was investigated with NONMEM software. We searched for all patient covariates potentially increasing accuracy of the model. The prognostic factors regarding 2 year biochemical RFS (bRFS) were assessed using univariate (log-rank) and multivariate analysis (Cox model).  Results: The best model describing PSA post-operative decrease was bi-compartmental. Only inclusion of “biochemical relapse” covariate (RLPS: Yes=1, No=0) statistically improved PSA elimination prediction. The final model was: [CLPSA= 0.0320 -0.0141 * RLPS]. There was a great agreement between predicted and observed PSA values. The significant prognostic factors associated with a better 2 year bRFS with univariate analysis were CLPSA >0.0234 (2 year bRFS=92.8% vs 66.7%, p=0.002) as well as preoperative PSA
Abstract LB-240: Clustering of phospho-proteins targeted by enzastaurin identifies significant biomarker association with patient outcome and novel associations between biomarker groupings in a glioblastoma multiforme cohort
Authors: Marisa Dolled-Fillhart, Robert Pinard, Don Waldron, Agnes Ang, Leo Goodrich, Scott Myrand, Don Thornton, Jeremy Graff, Brian Mullaney
Journal: Cancer Research (2008)

Abstract Introduction: Enzastaurin (LY317615.HCl) is a novel acyclic bisindolylmaleimide currently in Phase II clinical trials in combination with temozolomide and radiation for the front-line treatment of glioblastoma multiforme. Enzastaurin was identified as an ATP-competitive inhibitor of PKC-β subsequently as an inhibitor of other AGC-family kinases, including other PKC isoforms, p90RSK, GSK3β, and p70S6K. In a wide array of human cancer cell lines, including glioblastoma cell lines, enzastaurin treatment blocks signaling through the PI3 kinase/AKT/mTOR pathway. Accordingly, enzastaurin suppresses the phosphorylation of GSK3Bser9, AKTser473, CREBser133, and the S6 ribosomal protein at ser235/236 and ser240/244. We therefore sought to evaluate the levels of these key phosphorylation events in a series of primary human glioblastoma multiforme tissues in order to determine whether any or all of these phosphorylation events might be related to patient survival. Methods: A retrospective glioblastoma multiforme cohort of 115 patients was evaluated by quantitative immunofluoresence using AQUA® analysis for PhosphoCREB ser133, PhosphoS6 ser240/244, PhosphoGSK3B ser9, and total GSK3B. AQUA® technology quantitatively measured protein expression in patient samples, allowing for relative concentrations of the phosphorylated markers to be calculated and grouping of patients by clustering of AQUA® scores. Results: Spearman-Rho analysis identified strong direct correlations between PhosphoCREB ser133 and PhosphoS6 ser240/244 and between PhosphoCREB ser133 and PhosphoGSK3Bser9 expression in this cohort of patients. Univariate Kaplan Meier survival analysis of these patients based on clustered AQUA® scores revealed that these markers were indeed inversely related to disease-specific survival (phosphoGSK3B ser9 P&amp;lt;0.05). Multiparametric Correlative Discovery™ analysis also indicated a strong association of the cluster of patients with low levels of phosphoprotein expression and better survival. Conclusions: These data reveal that the signaling pathways targeted by enzastaurin were activated specifically in patients with the poorest survival and also suggest that these phosphomarkers, alone or in concert, may be useful for patient stratification.
In the lifeboat
Authors: Gloria Onwuneme
Journal: BMJ (2013)

In 1841, the sailing ship the William Brown , which was carrying 65 Scottish and Irish emigrants who were searching for a new life in the United States, hit an iceberg and sank. The ship had just two lifeboats, and only half the passengers managed to get a place on board. These survivors were to face another danger, however. The next night, the passengers of one lifeboat, worried that their vessel was in danger of being submerged, quietly pushed 16 of their number overboard. This chilling story has become a paradigm case for “lifeboat ethics,” which tackles the question of whom medicine should save when resources are scarce.

But, Thieves of Virtue: When Bioethics Stole Medicine by Tom Koch, questions the assumptions that underlie lifeboat ethics, and, indeed, much of modern medical ethics. …
PhyloToL: A Taxon/Gene-Rich Phylogenomic Pipeline to Explore Genome Evolution of Diverse Eukaryotes
Authors: Mario A Cerón-Romero, Xyrus X Maurer-Alcalá, Jean-David Grattepanche, Ying Yan, Miguel M Fonseca, L A Katz
Journal: Molecular Biology and Evolution (2019)

Abstract Estimating multiple sequence alignments (MSAs) and inferring phylogenies are essential for many aspects of comparative biology. Yet, many bioinformatics tools for such analyses have focused on specific clades, with greatest attention paid to plants, animals, and fungi. The rapid increase in high-throughput sequencing (HTS) data from diverse lineages now provides opportunities to estimate evolutionary relationships and gene family evolution across the eukaryotic tree of life. At the same time, these types of data are known to be error-prone (e.g., substitutions, contamination). To address these opportunities and challenges, we have refined a phylogenomic pipeline, now named PhyloToL, to allow easy incorporation of data from HTS studies, to automate production of both MSAs and gene trees, and to identify and remove contaminants. PhyloToL is designed for phylogenomic analyses of diverse lineages across the tree of life (i.e., at scales of &gt;100 My). We demonstrate the power of PhyloToL by assessing stop codon usage in Ciliophora, identifying contamination in a taxon- and gene-rich database and exploring the evolutionary history of chromosomes in the kinetoplastid parasite Trypanosoma brucei, the causative agent of African sleeping sickness. Benchmarking PhyloToL’s homology assessment against that of OrthoMCL and a published paper on superfamilies of bacterial and eukaryotic organellar outer membrane pore-forming proteins demonstrates the power of our approach for determining gene family membership and inferring gene trees. PhyloToL is highly flexible and allows users to easily explore HTS data, test hypotheses about phylogeny and gene family evolution and combine outputs with third-party tools (e.g., PhyloChromoMap, iGTP).
How are we measuring physical activity and sedentary behaviour in the four home nations of the UK? A narrative review of current surveillance measures and future directions
Authors: Tessa Strain, Karen Milton, Philippa Dall, Martyn Standage, Nanette Mutrie
Journal: British Journal of Sports Medicine (2019)

Background/objectives To explore and describe the comparability between the surveys of the UK home nations (England, Northern Ireland, Scotland, Wales) that monitor compliance with the Chief Medical Officers’ physical activity (PA) recommendations. We also suggest ways to improve the UK national PA and sedentary behaviour (SB) surveillance systems. Methods We identified national surveys that monitor PA and SB through searching UK-wide and devolved administration websites, the Global Observatory for Physical Activity Country Cards and the Active Healthy Kids Report Cards. Subsequently, we extracted information from survey documentation on the survey commissioners and contractors, method of administration, current questionnaire details relevant to the PA recommendations, questionnaire changes over the previous decade and the most recent prevalence figures. Results For adults and older adults, five surveys assess the moderate-to-vigorous PA (MVPA) recommendation, three assess muscle strengthening and three assess SB. For older adults only, three assess balance and co-ordination. For children, seven assess MVPA, none assess muscle strengthening and five assess SB. Only one survey reports on the under 5 PA recommendation. There is no part of the recommendations for which comparable estimates can be calculated across all four home nations. The greatest variation is among the SB questions and reporting. No survey has regularly used device-based measures. Conclusion UK surveillance of the PA recommendations is complex, undertaken separately in the home nations, using multiple surveys that cover adults and children separately. We recommend that the costs and benefits of harmonising the existing questionnaires are considered, along with the potential introduction of device-based measures.
Ignorance Isn’t Bliss: Retaining a Meaningful Comprehension Requirement for Consent to Research
Authors: Paul S. Appelbaum
Journal: The American Journal of Bioethics (2019)

In their summary of an impressive program of research on consent to biobanking studies, Beskow and Weinfurt (2019) adumbrate a key dilemma in research ethics: Informed consent to research would see...
Nasopharyngeal Aspirate (npa): is the Ideal viral sampling method in children with chronic respiratory symptoms
Authors: D. F. Wurzel, J. Marchant, I. M. Mackay, C. Y. Wang, T. P. Sloots, J. W. Upham, S. Yerkovich, S. Anderson-James, P. Baker, A. B. Chang
Journal: American Journal of Respiratory and Critical Care Medicine (2013)
Abstract P5-12-08: Not presented
Authors: A Botticelli, B Cerbelli, A Pisano, G Naso, M Monti, PA Ascierto, L Costarelli, V Magri, M Mauri, MG Pignataro, D Campagna, A Pernazza, M Nuti, L Fortunato, C Della Rocca, G D'Amati, P Marchetti
Journal: Cancer Research (2019)

Abstract This abstract was not presented at the conference. Citation Format: Botticelli A, Cerbelli B, Pisano A, Naso G, Monti M, Ascierto PA, Costarelli L, Magri V, Mauri M, Pignataro MG, Campagna D, Pernazza A, Nuti M, Fortunato L, Della Rocca C, D'Amati G, Marchetti P. Not presented [abstract]. In: Proceedings of the 2018 San Antonio Breast Cancer Symposium; 2018 Dec 4-8; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2019;79(4 Suppl):Abstract nr P5-12-08.
Discovery and Characterization of SY-1365, a Selective, Covalent Inhibitor of CDK7
Authors: Shanhu Hu, Jason J. Marineau, Nisha Rajagopal, Kristin B. Hamman, Yoon Jong Choi, Darby R. Schmidt, Nan Ke, Liv Johannessen, Michael J. Bradley, David A. Orlando, Sydney R. Alnemy, Yixuan Ren, Stephane Ciblat, Dana K. Winter, Anzhelika Kabro, Kevin T. Sprott, J. Graeme Hodgson, Christian C. Fritz, John P. Carulli, Emmanuelle di Tomaso, Eric R. Olson
Journal: Cancer Research (2019)

Abstract Recent studies suggest that targeting transcriptional machinery can lead to potent and selective anticancer effects in cancers dependent on high and constant expression of certain transcription factors for growth and survival. Cyclin-dependent kinase 7 (CDK7) is the catalytic subunit of the CDK-activating kinase complex. Its function is required for both cell-cycle regulation and transcriptional control of gene expression. CDK7 has recently emerged as an attractive cancer target because its inhibition leads to decreased transcript levels of oncogenic transcription factors, especially those associated with super-enhancers. Here, we describe a selective CDK7 inhibitor SY-1365, which is currently in clinical trials in populations of patients with ovarian and breast cancer (NCT03134638). In vitro, SY-1365 inhibited cell growth of many different cancer types at nanomolar concentrations. SY-1365 treatment decreased MCL1 protein levels, and cancer cells with low BCL2L1 (BCL-XL) expression were found to be more sensitive to SY-1365. Transcriptional changes in acute myeloid leukemia (AML) cell lines were distinct from those following treatment with other transcriptional inhibitors. SY-1365 demonstrated substantial antitumor effects in multiple AML xenograft models as a single agent; SY-1365–induced growth inhibition was enhanced in combination with the BCL2 inhibitor venetoclax. Antitumor activity was also observed in xenograft models of ovarian cancer, suggesting the potential for exploring SY-1365 in the clinic in both hematologic and solid tumors. Our findings support targeting CDK7 as a new approach for treating transcriptionally addicted cancers. Significance: These findings demonstrate the molecular mechanism of action and potent antitumor activity of SY-1365, the first selective CDK7 inhibitor to enter clinical investigation.
Bright spots, physical activity investments that work: INDER, the Institute of Sport and Recreation of Medellín in Colombia
Authors: Gary O"Donovan, Jenyfer Tabares García, Diana Brunal Berrocal, Nelson Gaviria García
Journal: British Journal of Sports Medicine (2019)

Figure 1 
How Institute of Sport and Recreation (INDER) embraces all seven best investments for physical activity.



The Institute of Sport and Recreation (INDER, according to its initials in Spanish) of Medellin in Colombia is the decentralised department of the mayor’s office that is responsible for promoting physical activity, sport and recreation. INDER was created in 1993 in response to the state’s new constitution of 1991, which stated in Article 52 that1: ‘The practice of sport… has as its goal the shaping of well-rounded people, protecting and enhancing their health.’ And, that: ‘Sport and recreation are part of one’s education and are the subject of public funds. The right of all people to sport, recreation and the best use of their free time is recognised. The state will promote these activities and will inspect, monitor and control sport and recreation organisations, whose structure and ownership must be democratic.’1 The mission and vision of INDER is still very much in keeping with the constitution: to promote physical activity, sport and recreation through programmes and facilities that help shape well-rounded people, help improve quality of life and help make Medellin a fairer, more inclusive and more tolerant city.2 

INDER has grown from a workforce of …
Sequencing Disparity in the Genomic Era
Authors: Kyle T David, Alan E Wilson, Kenneth M Halanych
Journal: Molecular Biology and Evolution (2019)

Advances in sequencing technology have resulted in the expectation that genomic studies will become more representative of organismal diversity. To test this expectation, we explored species representation of nonhuman eukaryotes in the Sequence Read Archive. Though species richness has been increasing steadily, species evenness is decreasing over time. Moreover, the top 1% most studied organisms increasingly represent a larger proportion of total experiments, demonstrating growing bias in favor of a small minority of species. To better understand molecular processes and patterns, genomic studies should reverse current trends by adopting more comparative approaches.
Abstract P011: Serum Magnesium and the Incidence of Coronary Heart Disease Over 20 Years of Follow-up: The Atherosclerosis Risk in Communities Study
Authors: Jeffrey R Misialek, Alvaro Alonso, Aaron R Folsom, Erin D Michos, Casey M Rebholz, Pamela L Lutsey
Journal: Circulation (2016)

Background: Low serum magnesium (Mg) may be linked to higher cardiovascular risk through impaired glucose levels, elevated blood pressure, chronic inflammation, impaired vasomotor tone or peripheral blood flow, and electrocardiogram abnormalities. Relatively few studies have examined the association of serum Mg and coronary heart disease (CHD). Hypothesis: Individuals with low serum Mg levels will have an increased risk for CHD. Methods: We studied 13,349 participants (75% white, 57% women, mean age 54) free of CHD at baseline from the Atherosclerosis Risk in Communities study. Serum Mg, assessed at baseline (1987-89) and a second visit (1990-92), was averaged. Incident CHD cases through 2012 were ascertained from hospital discharge codes and death certificates and adjudicated by physician review. Multivariate Cox proportional hazards regression was used to estimate hazard ratios and 95% confidence intervals. Interactions by age, race, and sex were tested. Results: Over a median follow-up time of 23.4 years, 1,606 incident CHD cases were identified. Low serum Mg was associated with higher CHD risk after adjustment for demographics and behaviors (Table, Model 2). Although the test for trend was significant, most of the excess risk was for the lowest Mg category. The association persisted after adjustment for potential mediators (Table, Mediation Model). There was no evidence of significant interactions between serum Mg and age, race, or sex. Conclusion: Low serum Mg was associated with higher CHD risk, which is consistent with the proposed mechanisms and prior studies that have suggested a relationship. Interventional primary prevention studies could be considered to evaluate whether raising low serum Mg levels might lower CHD risk.