tbuckley/cabot-search huggingface dataset:
Evolution of Population Structure in a Highly Social Top Predator, the Killer Whale
Authors: A. Rus Hoelzel, Jody Hey, Marilyn E. Dahlheim, Colin Nicholson, Vladimir Burkanov, Nancy Black
Journal: Molecular Biology and Evolution (2007)

Intraspecific resource partitioning and social affiliations both have the potential to structure populations, though it is rarely possible to directly assess the impact of these mechanisms on genetic diversity and population divergence. Here, we address this for killer whales (Orcinus orca), which specialize on prey species and hunting strategy and have long-term social affiliations involving both males and females. We used genetic markers to assess the structure and demographic history of regional populations and test the hypothesis that known foraging specializations and matrifocal sociality contributed significantly to the evolution of population structure. We find genetic structure in sympatry between populations of foraging specialists (ecotypes) and evidence for isolation by distance within an ecotype. Fitting of an isolation with migration model suggested ongoing, low-level migration between regional populations (within and between ecotypes) and small effective sizes for extant local populations. The founding of local populations by matrifocal social groups was indicated by the pattern of fixed mtDNA haplotypes in regional populations. Simulations indicate that this occurred within the last 20,000 years (after the last glacial maximum). Our data indicate a key role for social and foraging behavior in the evolution of genetic structure among conspecific populations of the killer whale.
Norepinephrine Uptake, Smooth Muscle Sensitivity, and Metabolizing Enzyme Activity in Rabbit Veins
Authors: JOHN A. BEVAN, DAVID W. HOSMER, BENGT LJUNG, BARBARA L. PEGRAM, CHE SU
Journal: Circulation Research (1974)

Some parameters of the adrenergic neuroeffector mechanism were measured in vitro in the central ear (near the base of the ear), common jugular, pulmonary, brachial, femoral, renal, superficial cervical, cephalic, and small saphenous veins, a branch of the deep circumflex iliac vein, the parietal branch of the internal iliac vein, branches of the anterior mesenteric vein, the inferior vena cava (immediately distal to the left renal vein), and a subcutaneous vein of the back. Although extraneuronal uptake of 3 H-norepinephrine was the same in all of the veins except the mesenteric, the neuronal uptake of norepinephrine varied widely. A number of veins, including the femoral and superficial cervical veins, showed no neuronal uptake, and the uptake of others, including the cephalic and mesenteric veins, was greater than that measured in any previously studied vascular tissue. The median effective dose for the contractile effect of norepinephrine on the veins was on the same order of magnitude as that for the aorta and the ear artery. Catechol-O-methyl transferase, but not monoamine oxidase, activity appeared to be related to innervation density. It is concluded that veins show a remarkable variation in the dimensions of their adrenergic parameters, particularly those related to innervation density.
Antiseptic Incision and Drainage in Empyema
Authors: F. R. Cross
Journal: BMJ (1882)

6ii the common Mole, a complete study of the earlier stages of the man- dibular arch yields the following results.In the Mole (Talpa europwa), which has, in the adult, extremely small ossicula auditfts, the embryonic mandible is as large as in the Sauropsida; the top of the bar forms a very distinct quadrate lobe, and there is below a short posterior and a long internal process.The rod then runs on, thick and solid, inside the thickening tissues which form the ramus, together with the internal branch of the third division of the fifth nerve and the chorda tympani from the seventh on its inner side, and the outer branch of the third division of the fifth on its outer side.The two Meckel's cartilages meet, unite, and form a basi-mandibular rod, which, hewever, does not become segmented off.
Development of a List of High-Risk Operations for Patients 65 Years and Older
Authors: Margaret L. Schwarze, Amber E. Barnato, Paul J. Rathouz, Qianqian Zhao, Heather B. Neuman, Emily R. Winslow, Gregory D. Kennedy, Yue-Yung Hu, Christopher M. Dodgion, Alvin C. Kwok, Caprice C. Greenberg
Journal: JAMA Surgery (2015)

No consensus exists regarding the definition of high-risk surgery in older adults. An inclusive and precise definition of high-risk surgery may be useful for surgeons, patients, researchers, and hospitals.
Changes in bronchial inflammation during acute exacerbations of chronic bronchitis
Authors: S. Gompertz, C. O'Brien, D.L. Bayley, S.L. Hill, R.A. Stockley
Journal: European Respiratory Journal (2001)

There are little data describing noncellular changes in bronchial inflammation during exacerbations of chronic bronchitis. The relationship between sputum colour and airway inflammation at presentation has been assessed during an exacerbation in patients with chronic bronchitis and a primary care diagnosis of chronic obstructive pulmonary disease. Sputum myeloperoxidase, neutrophil elastase, leukotriene B 4 (LTB 4 ), interleukin-8 (IL-8), sol:serum albumin ratio and serum C-reactive protein were measured in patients presenting with an exacerbation and mucoid (n=27) or purulent sputum (n=42). Mucoid exacerbations were associated with little bronchial or systemic inflammation at presentation, and sputum bacteriology was similar to that obtained in the stable state. Purulent exacerbations were associated with marked bronchial and systemic inflammation (p&lt;0.025 for all features) and positive sputum cultures (90%). Resolution was related to a significant reduction in LTB 4 (p&lt;0.01), but no change in IL-8, suggesting that LTB 4 may be more important in neutrophil recruitment in these mild, purulent exacerbations. In the stable state, IL-8 remained higher in patients who had experienced a purulent exacerbation (2p&lt;0.02). The presented results indicate that exacerbations of chronic bronchitis, defined by sputum colour, differ in the degree of bronchial and systemic inflammation. Purulent exacerbations are related to bacterial infection, and are associated with increased neutrophilic inflammation and increased leukotriene B 4 concentrations.
Point-of-Care Measured Platelet Inhibition Correlates With a Reduced Risk of an Adverse Cardiac Event After Percutaneous Coronary Intervention
Authors: Steven R. Steinhubl, J. David Talley, Gregory A. Braden, James E. Tcheng, Peter J. Casterella, David J. Moliterno, Frank I. Navetta, Peter B. Berger, Jeffrey J. Popma, George Dangas, Richard Gallo, David C. Sane, Jorge F. Saucedo, Gang Jia, A. Michael Lincoff, Pierre Theroux, David R. Holmes, Paul S. Teirstein, Dean J. Kereiakes
Journal: Circulation (2001)

Background —The optimal level of platelet inhibition with a glycoprotein (GP) IIb/IIIa antagonist necessary to minimize thrombotic complications in patients undergoing a percutaneous coronary intervention (PCI) is currently unknown. Methods and Results —Five hundred patients undergoing a PCI with the planned use of a GP IIb/IIIa inhibitor had platelet inhibition measured at 10 minutes, 1 hour, 8 hours, and 24 hours after the initiation of therapy with the Ultegra Rapid Platelet Function Assay (Accumetrics). Major adverse cardiac events (MACEs: composite of death, myocardial infarction, and urgent target vessel revascularization) were prospectively monitored, and the incidence correlated with the measured level of platelet function inhibition at all time points. One quarter of all patients did not achieve ≥95% inhibition 10 minutes after the bolus and experienced a significantly higher incidence of MACEs (14.4% versus 6.4%, P =0.006). Patients whose platelet function was &lt;70% inhibited at 8 hours after the start of therapy had a MACE rate of 25% versus 8.1% for those ≥70% inhibited ( P =0.009). By multivariate analysis, platelet function inhibition ≥95% at 10 minutes after the start of therapy was associated with a significant decrease in the incidence of a MACE (odds ratio 0.46, 95% CI 0.22 to 0.96, P =0.04). Conclusions —Substantial variability in the level of platelet function inhibition is achieved with GP IIb/IIIa antagonist therapy among patients undergoing PCI. The level of platelet function inhibition as measured by a point-of-care assay is an independent predictor for the risk of MACEs after PCI.
Validation of the paediatric logistic organ dysfunction (PELOD) score: prospective, observational, multicentre study
Authors: Stéphane Leteurtre, Alain Martinot, Alain Duhamel, François Proulx, Bruno Grandbastien, Jacques Cotting, Ronald Gottesman, Ari Joffe, Jurg Pfenninger, Philippe Hubert, Jacques Lacroix, Francis Leclerc
Journal: The Lancet (2003)
Impact of a Peer-Delivered Telephone Intervention for Women Experiencing a Breast Cancer Recurrence
Authors: Carolyn Cook Gotay, Carol M. Moinpour, Joseph M. Unger, Caroline S. Jiang, Dorothy Coleman, Silvana Martino, Beverly J. Parker, James D. Bearden, Shaker Dakhil, Howard M. Gross, Scott Lippman, Kathy S. Albain
Journal: Journal of Clinical Oncology (2007)

Purpose A first breast cancer recurrence creates considerable distress, yet few psychosocial interventions directed at this population have been reported. The Southwest Oncology Group conducted a phase III randomized trial to evaluate the effectiveness of a brief telephone intervention. Patients and Methods Three hundred five women experiencing a first recurrence of breast cancer were randomly assigned to standard care or intervention. The intervention consisted of four to eight telephone calls delivered over a 1-month period. The calls were conducted by trained peer counselors at a breast cancer advocacy organization, the Y-ME National Breast Cancer Organization, and followed a standard curriculum. Psychosocial distress (Cancer Rehabilitation Evaluation System–Short Form [CARES-SF]) and depressive symptoms (Center for Epidemiologic Studies Depression Scale [CES-D]) outcomes were assessed at baseline and 3 and 6 months. The 3-month assessment was the primary end point and is the focus of this article. Results Analysis revealed no differences in distress or depressive symptoms at 3 months between the intervention and control groups; at 3 months, 70% of control patients and 66% of intervention patients reported psychosocial distress, and 40% of control patients and 47% of intervention patients exhibited depressive symptoms. Conclusion Telephone peer counseling did not lead to better psychosocial outcomes. The persistent distress in these women supports the urgent need for the development and testing of more intensive or different supportive interventions for this group of patients.
Rosuvastatin: winner in the statin wars, patients' health notwithstanding
Authors: S. Wolfe
Journal: BMJ (2015)

More is spent in the US on rosuvastatin than any other statin. Yet the evidence of its health benefits has always been weak and there is growing evidence of harmful side effects. <b>Sidney Wolfe</b> explains why he thinks the drug should have been withdrawn and why it should not be used
COX-2 inhibition with rofecoxib does not increase intestinal permeability in healthy subjects: a double blind crossover study comparing rofecoxib with placebo and indomethacin
Authors: G Sigthorsson
Journal: Gut (2000)

<h3>BACKGROUND</h3> Acute and chronic use of non-steroidal anti-inflammatory drugs can increase intestinal permeability. Rofecoxib, which selectively inhibits cyclooxygenase 2 (COX-2), is a novel anti-inflammatory drug with the potential to produce minimal gastrointestinal toxic effects while retaining clinical efficacy. <h3>AIMS</h3> To assess the potential for rofecoxib to affect the intestine adversely, in comparison with placebo and indomethacin. <h3>SUBJECTS</h3> Thirty nine healthy subjects (aged 24–30 years). <h3>METHOD</h3> We performed a four period crossover trial to assess intestinal permeability before and after seven days of treatment. Permeability was measured by the urinary ratio of chromium-51 labelled ethylene diamine tetraacetate (<sup>51</sup>CrEDTA)/l-rhamnose (five hour collection). <h3>RESULTS</h3> Indomethacin 50 mg three times daily produced greater increases in intestinal permeability compared with placebo or rofecoxib (25 or 50 mg) (p⩽0.001); rofecoxib was not significantly different from placebo. Mean day 7 to baseline ratios (95% confidence intervals) for<sup>51</sup>CrEDTA/l-rhamnose were 0.97 (0.82, 1.16), 0.80 (0.68, 0.95), 0.98 (0.82, 1.17), and 1.53 (1.27, 1.85) for placebo, rofecoxib 25 mg, rofecoxib 50 mg, and indomethacin groups, respectively. Rofecoxib was generally well tolerated. <h3>CONCLUSION</h3> In this study, treatment for one week with indomethacin 50 mg three times daily significantly increased intestinal permeability compared with placebo, while treatment with rofecoxib 25 mg or 50 mg daily did not. The absence of a significant effect of rofecoxib on intestinal permeability at doses at least twice those recommended to treat osteoarthritis was consistent with other studies that have demonstrated little or no injury to the gastrointestinal mucosa associated with rofecoxib therapy.
Nails - more than just an ectodermal appendage: the genetics behind isolated nail disorders
Authors: R.C. Betz
Journal: British Journal of Dermatology (2015)

Journal Article Nails – more than just an ectodermal appendage: the genetics behind isolated nail disorders Get access R.C. Betz R.C. Betz Institute of Human Genetics Biomedical Center (BMZ) University of Bonn Sigmund‐Freud‐Str. 25 D‐53127 Bonn Germany https://orcid.org/0000-0001-5024-3623 Search for other works by this author on: Oxford Academic Google Scholar British Journal of Dermatology, Volume 173, Issue 4, 1 October 2015, Page 886, https://doi.org/10.1111/bjd.14148 Published: 01 October 2015
THE EFFECT OF CHANGES IN THE PULMONARY VASCULAR BED PRODUCED BY ATROPINE, PULMONARY ENGORGEMENT, AND POSITIVE-PRESSURE BREATHING ON DIFFUSING AND MECHANICAL PROPERTIES OF THE LUNG*
Authors: Walter J. Daly, Joseph C. Ross, Roy H. Behnke
Journal: Journal of Clinical Investigation (1963)

Several factors probably have some role in de- termining the volume of the effectively ventilated pulmonary capillary bed, including pulmonary blood flow, pulmonary vascular pressures, pul- monary blood volume, alveolar and blood gas ten- sions, and mechanical effects of ventilation.Others have found that atropine sulfate, 2.0 mg iv, increases cardiac output (1, 2), decreases central venous pressure (1, 2), and affects the dis- tribution of the blood volume as shown by plethys- mographic study of extremity venous volume (3).This drug, then, provides an unusual rearrange- ment of some of the determinants of pulmonary capillary function and, for the present study, was used either alone or in combination with positivepressure breathing or pulmonary vascular en- gorgement produced by G-suit inflation.This study was carried out to provide further information concerning the interaction of cardiac output, pulmonary vascular pressure, and pulmonary blood volume as determinants of the vol- ume of effectively ventilated capillaries by de- termining the effects of changes in the pulmonary vascular bed produced by atropine, pulmonary engorgement, and positive-pressure breathing on the diffusing and mechanical properties of the lung.
CRISPR-mediated genome editing of Plasmodium falciparum malaria parasites
Authors: Marcus Cs Lee, David A Fidock
Journal: Genome Medicine (2014)

The development of the CRISPR-Cas system is revolutionizing genome editing in a variety of organisms. The system has now been used to manipulate the genome of Plasmodium falciparum, the most lethal malaria-causing species. The ability to generate gene deletions or nucleotide substitutions rapidly and economically promises to accelerate the analysis of novel drug targets and to help elucidate the function of specific genes or gene families, while complementing genome-wide association studies.
O4.05 * GENETIC DIVERSITY AND INTRA-TUMOR HETEROGENEITY IN HUMAN GLIOBLASTOMA
Authors: S. G. M. Piccirillo, I. Spiteri, A. Sottoriva, A. Touloumis, P. Collins, C. Curtis, J. Marioni, S. Tavare', C. Watts
Journal: Neuro-Oncology (2014)

BACKGROUND: Glioblastoma (GB) is the most common and aggressive primary brain malignancy. The disease is advanced at the time of clinical presentation and response to treatment may be confounded by clonal heterogeneity and differential patterns of resistance in spatially distinct parts of the same tumor. However, we do not understand how this complex environment evolves. Accumulating evidence suggests that intra-tumor heterogeneity is likely to be the key to understanding treatment failure, however the dynamics of such heterogeneity are still poorly understood. METHODS: Using a Fluorescence-Guided Multiple Sampling technique we obtained samples from the tumor mass, the sub-ependymal zone and the non-fluorescent tumor margin. We performed an integrated genomic analysis based on copy number alteration and molecular clock data to develop a phylogenetic and spatial reconstruction of tumor evolution in individual patients. Temporal analysis was performed using patient-derived xenografts obtained by serial transplantation of tumor cells in immunosuppressed mice. RESULTS: Phylogenetic reconstruction of the fragments from each GB identifies copy number alterations in EGFR and CDKN2A/B/p14ARF as early evolutionary events while aberrations in PDGFRA and PTEN occur later in the disease progression. Transcriptional profiling reveals that many patients display multiple GB subtypes within their tumor while deconstruction of the clonal organization of each tumor fragment at single-molecule level identified multiple coexisting cell lineages. Ancestral tumor precursors that gave rise to the tumor mass were found in the sub-ependymal zone of a subset of GB patients. When used in in vivo experiments, tumor cells show variable competitive capacity for disease propagation and further genetic diversification suggesting that GB evolves through complex dynamics of sub-clonal fitness advantage and acquisitions of mutations and copy number alterations. CONCLUSION: Our integrated genomic analysis reports the evolution of GB in individual patients across multiple spatial scales. Our data reveals early clonal diversification generating a genetically complex and highly evolved disease environment at clinical presentation. In serial transplant experiments, subclonal growth advantage results in genetic diversification that ultimately produces additional heterogeneity. We propose that these fundamental patient-specific tumor evolutionary dynamics underlie clinical phenotypic heterogeneity and may have implications for the emergence of resistant disease.
Identification of mismatch repair gene mutations in young patients with colorectal cancer and in patients with multiple tumours associated with hereditary non-polyposis colorectal cancer
Authors: R C Niessen, M J W Berends, Y Wu, R H Sijmons, H Hollema, M J L Ligtenberg, H E K de Walle, E G E de Vries, A Karrenbeld, C H C M Buys, A G J van der Zee, R M W Hofstra, J H Kleibeuker
Journal: Gut (2006)

Patients with early-onset colorectal cancer (CRC) or those with multiple tumours associated with hereditary non-polyposis colorectal cancer (HNPCC) raise suspicion of the presence of germline DNA mismatch repair (MMR) gene mutations.To analyse the value of family history, microsatellite instability (MSI) analysis and MMR protein staining in the tumour to predict the presence of an MMR gene mutation in such patients.In 281 patients diagnosed with CRC before the age of 50 years or with CRC and at least one additional HNPCC-associated cancer, germline mutation analysis in MLH1, MSH2 and MSH6 was carried out with denaturing gradient gel electrophoresis and multiplex ligation-dependent probe amplification. MSI analysis with five consensus markers and MMR protein staining for MLH1, MSH2 and MSH6 were carried out in the tumours.25 pathogenic mutations (8 in MLH1, 9 in MSH2 and 8 in MSH6) were found. MSI analysis missed three and immunohistochemistry (IHC) missed two mutation carriers. Sensitivities of family history, MSI analysis and IHC for the presence of a mutation were 76%, 82% and 88%, specificities were 64%, 70% and 84%, and positive predictive values were 19%, 23% and 38%, respectively. Multivariate analysis showed the highest odds ratio for IHC (38.3, 95% confidence interval 9.0 to 184). Prevalence of pathogenic germline MMR gene mutations in patients with CRC before the age of 50 years was 6% and in those with > or =2 HNPCC-associated tumours was 22%. In the second group, no mutation carriers were found among the 29 patients who were diagnosed with their first tumour after the age of 60 years.Family history, MSI analysis and IHC are indicative parameters to select patients with CRC for MMR gene mutation analysis. The data show that IHC is the best single selection criterion.
STAT3 Mediates Resistance to MEK Inhibitor through MicroRNA miR-17
Authors: Bingbing Dai, Jieru Meng, Michael Peyton, Luc Girard, William G. Bornmann, Lin Ji, John D. Minna, Bingliang Fang, Jack A. Roth
Journal: Cancer Research (2011)

AZD6244 is a small molecule inhibitor of the MEK (MAP/ERK kinase) pathway currently in clinical trials. However, the mechanisms mediating intrinsic resistance to MEK inhibition are not fully characterized. To define molecular mechanisms of MEK inhibitor resistance, we analyzed responses of 38 lung cancer cell lines following AZD6244 treatment and their genome-wide gene expression profiles and identified a panel of genes correlated with sensitivity or resistance to AZD6244 treatment. In particular, ingenuity pathway analysis revealed that activation of the STAT3 pathway was associated with MEK inhibitor resistance. Inhibition of this pathway by JSI-124, a STAT3-specific small molecule inhibitor, or with STAT3-specific siRNA sensitized lung cancer cells to AZD6244 and induced apoptosis. Moreover, combining a STAT3 inhibitor with AZD6244 induced expression of BIM and PARP cleavage, whereas activation of the STAT3 pathway inhibited BIM expression and elicited resistance to MEK inhibitors. We found that the STAT3-regulated microRNA miR-17 played a critical role in MEK inhibitor resistance, such that miR-17 inhibition sensitized resistant cells to AZD6244 by inducing BIM and PARP cleavage. Together, these results indicated that STAT3-mediated overexpression of miR-17 blocked BIM expression and caused resistance to AZD6244. Our findings suggest novel approaches to overcome resistance to MEK inhibitors by combining AZD6244 with STAT3 or miR-17 inhibitors.