tbuckley/cabot-search huggingface dataset:
The western painted turtle genome, a model for the evolution of extreme physiological adaptations in a slowly evolving lineage
Authors: H Bradley Shaffer, Patrick Minx, Daniel E Warren, Andrew M Shedlock, Robert C Thomson, Nicole Valenzuela, John Abramyan, Chris T Amemiya, Daleen Badenhorst, Kyle K Biggar, Glen M Borchert, Christopher W Botka, Rachel M Bowden, Edward L Braun, Anne M Bronikowski, Benoit G Bruneau, Leslie T Buck, Blanche Capel, Todd A Castoe, Mike Czerwinski, Kim D Delehaunty, Scott V Edwards, Catrina C Fronick, Matthew K Fujita, Lucinda Fulton, Tina A Graves, Richard E Green, Wilfried Haerty, Ramkumar Hariharan, Omar Hernandez, LaDeana W Hillier, Alisha K Holloway, Daniel Janes, Fredric J Janzen, Cyriac Kandoth, Lesheng Kong, AP Jason de Koning, Yang Li, Robert Literman, Suzanne E McGaugh, Lindsey Mork, Michelle O'Laughlin, Ryan T Paitz, David D Pollock, Chris P Ponting, Srihari Radhakrishnan, Brian J Raney, Joy M Richman, John St John, Tonia Schwartz, Arun Sethuraman, Phillip Q Spinks, Kenneth B Storey, Nay Thane, Tomas Vinar, Laura M Zimmerman, Wesley C Warren, Elaine R Mardis, Richard K Wilson
Journal: Genome biology (2013)

We describe the genome of the western painted turtle, Chrysemys picta bellii, one of the most widespread, abundant, and well-studied turtles. We place the genome into a comparative evolutionary context, and focus on genomic features associated with tooth loss, immune function, longevity, sex differentiation and determination, and the species' physiological capacities to withstand extreme anoxia and tissue freezing.Our phylogenetic analyses confirm that turtles are the sister group to living archosaurs, and demonstrate an extraordinarily slow rate of sequence evolution in the painted turtle. The ability of the painted turtle to withstand complete anoxia and partial freezing appears to be associated with common vertebrate gene networks, and we identify candidate genes for future functional analyses. Tooth loss shares a common pattern of pseudogenization and degradation of tooth-specific genes with birds, although the rate of accumulation of mutations is much slower in the painted turtle. Genes associated with sex differentiation generally reflect phylogeny rather than convergence in sex determination functionality. Among gene families that demonstrate exceptional expansions or show signatures of strong natural selection, immune function and musculoskeletal patterning genes are consistently over-represented.Our comparative genomic analyses indicate that common vertebrate regulatory networks, some of which have analogs in human diseases, are often involved in the western painted turtle's extraordinary physiological capacities. As these regulatory pathways are analyzed at the functional level, the painted turtle may offer important insights into the management of a number of human health disorders.
Children of Depressed Mothers 1 Year After the Initiation of Maternal Treatment: Findings From the STAR*D-Child Study
Authors: Daniel J. Pilowsky, Priya Wickramaratne, Ardesheer Talati, Min Tang, Carroll W. Hughes, Judy Garber, Erin Malloy, Cheryl King, Gabrielle Cerda, A. Bela Sood, Jonathan E. Alpert, Madhukar H. Trivedi, Maurizio Fava, A. John Rush, Stephen Wisniewski, Myrna M. Weissman
Journal: American Journal of Psychiatry (2008)

Maternal depression is a consistent and well-replicated risk factor for child psychopathology. The authors examined the changes in psychiatric symptoms and global functioning in children of depressed women 1 year following the initiation of treatment for maternal major depressive disorder.Participants were 1) 151 women with maternal major depression who were enrolled in the Sequenced Treatment Alternatives to Relieve Depression (STAR*D) study and 2) their eligible offspring who, along with the mother, participated in the child STAR*D (STAR*D-Child) study (mother-child pairs: N=151). The STAR*D study was a multisite study designed to determine the comparative effectiveness and acceptability of various treatment options for adult outpatients with nonpsychotic major depressive disorder. The STAR*D-Child study examined children of depressed women at baseline and involved periodic follow-ups for 1 year after the initiation of treatment for maternal major depressive disorder to ascertain the following data: 1) whether changes in children's psychiatric symptoms were associated with changes in the severity of maternal depression and 2) whether outcomes differed among the offspring of women who did and did not remit (mother-child pairs with follow-up data: N=123). Children's psychiatric symptoms in the STAR*D-Child study were assessed using the Schedule for Affective Disorders and Schizophrenia for School-Age Children-Present and Lifetime Version (K-SADS-PL), and maternal depression severity in the STAR*D study was assessed by an independent clinician, using the 17-item Hamilton Depression Rating Scale (HAM-D).During the year following the initiation of treatment, maternal depression severity and children's psychiatric symptoms continued to decrease over time. Decreases in the number of children's psychiatric symptoms were significantly associated with decreases in maternal depression severity. When children's outcomes were examined separately, a statistically significant decrease in symptoms was evident in the offspring of women who remitted early (i.e., within the first 3 months after the initiation of treatment for maternal depression) or late (i.e., over the 1-year follow-up interval) but not in the offspring of nonremitting women.Continued efforts to treat maternal depression until remission is achieved are associated with decreased psychiatric symptoms and improved functioning in the offspring.
B cell-stimulatory factor 1 (BSF-1) promotes growth of helper T cell lines.
Authors: R Fernandez-Botran, P H Krammer, T Diamantstein, J W Uhr, E S Vitetta
Journal: The Journal of Experimental Medicine (1986)

T cell-derived supernatants (SN) that contain B cell-stimulatory factor 1 (BSF-1) and lack IL-2 promote the growth of the IL-2-dependent T cell line, HT-2, as well as three other clones or lines of T cells that can provide help to B cells. The BSF-1 purified from these SNs promotes growth of HT-2 cells approximately 50% as effectively as purified IL-2. A potential involvement for contaminating IL-2 in the BSF-1 preparations was excluded by the demonstration that anti-BSF-1 mAbs blocked the BSF-1-induced growth of HT-2 cells; in contrast, these antibodies did not block the IL-2-induced proliferation of the HT-2 cells. In addition, anti-IL-2 mAbs or anti-IL-2-R antibodies blocked the HT-2 growth-promoting activity of purified IL-2, but not BSF-1. Finally, BSF-1 promoted only a very modest growth of Con A-induced T cell blasts, and failed to induce significant growth in seven other cytotoxic, alloreactive, and long-term T cell lines. Taken together, these results indicate that in addition to its known effects on resting and LPS-stimulated B cells, BSF-1 can promote growth of certain subsets of activated T cells, in particular, those that provide help to B cells.
Prognostic Factors in Patients With Advanced Cancer: Use of the Patient-Generated Subjective Global Assessment in Survival Prediction
Authors: Lisa Martin, Sharon Watanabe, Robin Fainsinger, Francis Lau, Sunita Ghosh, Hue Quan, Marlis Atkins, Konrad Fassbender, G. Michael Downing, Vickie Baracos
Journal: Journal of Clinical Oncology (2010)

To determine whether elements of a standard nutritional screening assessment are independently prognostic of survival in patients with advanced cancer.A prospective nested cohort of patients with metastatic cancer were accrued from different units of a Regional Palliative Care Program. Patients completed a nutritional screen on admission. Data included age, sex, cancer site, height, weight history, dietary intake, 13 nutrition impact symptoms, and patient- and physician-reported performance status (PS). Univariate and multivariate survival analyses were conducted. Concordance statistics (c-statistics) were used to test the predictive accuracy of models based on training and validation sets; a c-statistic of 0.5 indicates the model predicts the outcome as well as chance; perfect prediction has a c-statistic of 1.0.A training set of patients in palliative home care (n = 1,164) was used to identify prognostic variables. Primary disease site, PS, short-term weight change (either gain or loss), dietary intake, and dysphagia predicted survival in multivariate analysis (P < .05). A model including only patients separated by disease site and PS with high c-statistics between predicted and observed responses for survival in the training set (0.90) and validation set (0.88; n = 603). The addition of weight change, dietary intake, and dysphagia did not further improve the c-statistic of the model. The c-statistic was also not altered by substituting physician-rated palliative PS for patient-reported PS.We demonstrate a high probability of concordance between predicted and observed survival for patients in distinct palliative care settings (home care, tertiary inpatient, ambulatory outpatient) based on patient-reported information.
Somatic<i>CALR</i>Mutations in Myeloproliferative Neoplasms with Nonmutated<i>JAK2</i>
Authors: J. Nangalia, C.E. Massie, E.J. Baxter, F.L. Nice, G. Gundem, D.C. Wedge, E. Avezov, J. Li, K. Kollmann, D.G. Kent, A. Aziz, A.L. Godfrey, J. Hinton, I. Martincorena, P. Van Loo, A.V. Jones, P. Guglielmelli, P. Tarpey, H.P. Harding, J.D. Fitzpatrick, C.T. Goudie, C.A. Ortmann, S.J. Loughran, K. Raine, D.R. Jones, A.P. Butler, J.W. Teague, S. O'Meara, S. McLaren, M. Bianchi, Y. Silber, D. Dimitropoulou, D. Bloxham, L. Mudie, M. Maddison, B. Robinson, C. Keohane, C. Maclean, K. Hill, K. Orchard, S. Tauro, M.-Q. Du, M. Greaves, D. Bowen, B.J.P. Huntly, C.N. Harrison, N.C.P. Cross, D. Ron, A.M. Vannucchi, E. Papaemmanuil, P.J. Campbell, A.R. Green
Journal: New England Journal of Medicine (2013)

Somatic mutations in the Janus kinase 2 gene (JAK2) occur in many myeloproliferative neoplasms, but the molecular pathogenesis of myeloproliferative neoplasms with nonmutated JAK2 is obscure, and the diagnosis of these neoplasms remains a challenge.
Transient memory impairment and transient global amnesia induced by photodynamic therapy
Authors: M. Reinholz, M.V. Heppt, F.S. Hoffmann, N. Lummel, T. Ruzicka, P. Lehmann, C. Berking
Journal: British Journal of Dermatology (2015)

Photodynamic therapy (PDT) is a commonly used and effective treatment option for nonmelanoma skin cancer. Apart from local side‐effects such as pain, oedema and erythema, no major adverse events occur in the majority of cases. Here we report on five patients who developed memory deficits such as transient global amnesia immediately after PDT for actinic keratosis. All PDT treatments were performed according to standard therapy protocols. The reported patients had a memory gap for the entire procedure, as well as for the consecutive emergency medical care. Other common neurological causes such as stroke or epileptic seizures were excluded. No focal neurological deficits were detectable. The symptoms had a fairly rapid onset following red‐light illumination and were reversible without sequelae within 1–24 h. No correlation of the condition and pain during the illumination could be revealed. Magnetic resonance imaging of the brain revealed punctuated lesions in the hippocampus as a potential morphological correlate in one patient. The association between amnestic syndromes and PDT is novel and has not previously been reported. Even though PDT is considered a safe treatment modality, the possibility of neurological adverse events, albeit rare, should be kept in mind.
Rapamycin Inhibits Growth of Premalignant and Malignant Mammary Lesions in a Mouse Model of Ductal Carcinoma <i>In situ</i>
Authors: Ruria Namba, Lawrence J.T. Young, Craig K. Abbey, Lisa Kim, Patrizia Damonte, Alexander D. Borowsky, Jinyi Qi, Clifford G. Tepper, Carol L. MacLeod, Robert D. Cardiff, Jeffrey P. Gregg
Journal: Clinical Cancer Research (2006)

Rapamycin has been shown to have antitumor effects in various tumor models. To study the effect of rapamycin at different stages of breast cancer development, we used two unique mouse models of breast cancer with activated phosphatidylinositol 3-kinase (PI3K) pathway. Met-1 tumors are highly invasive and metastatic, and mammary intraepithelial neoplasia-outgrowths (MIN-O), a model for human ductal carcinoma in situ, are transplantable premalignant mammary lesions that develop invasive carcinoma with predictable latencies. Both of these models were derived from mammary lesions in Tg(MMTV-PyV-mT) mice.Met-1 tumors were used to study the effect of rapamycin treatment on invasive disease. Transplanted MIN-O model was used to study the effect of rapamycin on premalignant mammary lesions. Animals were in vivo micro-positron emission tomography imaged to follow the lesion growth and transformation to tumor during the treatment. Cell proliferation, angiogenesis, and apoptosis was assayed by immunohistochemistry.Rapamycin inhibited in vitro tumor cell proliferation and in vivo Met-1 tumor growth. The growth inhibition was correlated with dephosphorylation of mammalian target of rapamycin (mTOR) targets. Rapamycin treatment significantly reduced the growth of the premalignant MIN-O lesion, as well as tumor incidence and tumor burden. Growth inhibition was associated with reduced cell proliferation and angiogenesis and increased apoptosis.In PyV-mT mouse mammary models, rapamycin inhibits the growth of premalignant lesions and invasive tumors. Although the inhibitory effect of rapamycin was striking, rapamycin treatment did not completely obliterate the lesions.
Bronchoscopic thermal vapour ablation therapy in the management of heterogeneous emphysema
Authors: Gregory Snell, Felix J.F. Herth, Peter Hopkins, Kimberley M. Baker, Christian Witt, Mark H. Gotfried, Arschang Valipour, Manfred Wagner, Franz Stanzel, Jim J. Egan, Steven Kesten, Armin Ernst
Journal: European Respiratory Journal (2011)

The need for a less invasive procedure than surgical lung volume reduction that can produce consistent improvements with reduced morbidity remains a medical goal in patients with emphysema. We sought to determine the effect of bronchoscopic thermal vapour ablation (BTVA) on lung volumes and outcomes in patients with emphysema. 44 patients with upper lobe-predominant emphysema were treated unilaterally with BTVA. Entry criteria included: age 40–75 yrs, forced expiratory volume in 1 s (FEV 1 ) 15–45% predicted, previous pulmonary rehabilitation and a heterogeneity index (tissue/air ratio of lower lobe/upper lobe) from high-resolution computed tomography (HRCT) ≥1.2. Changes in FEV 1 , St George's Respiratory Questionnaire (SGRQ), 6-min walk distance (6MWD), modified Medical Research Council (mMRC) dyspnoea score, and hyperinflation were measured at baseline, and 3 and 6 months post-BTVA. At 6 months, mean± se FEV 1 improved by 141±26 mL (p&lt;0.001) and residual volume was reduced by 406±113 mL (p&lt;0.0001). SGRQ total score improved by 14.0±2.4 points (p&lt;0.001), with 73% improving by ≥4 points. Improvements were observed in 6MWD (46.5±10.6 m) and mMRC dyspnoea score (0.9±0.2) (p&lt;0.001 for both). Lower respiratory events (n=11) were the most common adverse event and occurred most often during the initial 30 days. BTVA therapy results in clinically relevant improvements in lung function, quality of life and exercise tolerance in upper lobe predominant emphysema.
Association of methotrexate and tumour necrosis factor antagonists with risk of infectious outcomes including opportunistic infections in the CORRONA registry
Authors: J D Greenberg, G Reed, J M Kremer, E Tindall, A Kavanaugh, C Zheng, W Bishai, M C Hochberg
Journal: Annals of the Rheumatic Diseases (2009)

Objective: To examine the association of methotrexate (MTX) and tumour necrosis factor (TNF) antagonists with the risk of infectious outcomes including opportunistic infections in patients with rheumatoid arthritis (RA). Methods: Patients with RA enrolled in the Consortium of Rheumatology Researchers of North America (CORRONA) registry prescribed MTX, TNF antagonists or other disease-modifying antirheumatic drugs (DMARDs) were included. The primary outcomes were incident overall and opportunistic infections. Incident rate ratios were calculated using generalised estimating equation Poisson regression models adjusted for demographics, comorbidities and RA disease activity measures. Results: A total of 7971 patients with RA were followed. The adjusted rate of infections per 100 person-years was increased among users of MTX (30.9, 95% CI 29.2 to 32.7), TNF antagonists (40.1, 95% CI 37.0 to 43.4) and a combination of MTX and TNF antagonists (37.1, 95% CI 34.9 to 39.3) compared with users of other non-biological DMARDs (24.5, 95% CI 21.8 to 27.5). The adjusted incidence rate ratio (IRR) was increased in patients treated with MTX (IRR 1.30, 95% CI 1.12 to 1.50) and TNF antagonists (IRR 1.52, 95% CI 1.30 to 1.78) compared with those treated with other DMARDs. TNF antagonist use was associated with an increased risk of opportunistic infections (IRR 1.67, 95% CI 0.95 to 2.94). Prednisone use was associated with an increased risk of opportunistic infections (IRR 1.63, 95% CI 1.20 to 2.21) and an increased risk of overall infection at doses &gt;10 mg daily (IRR 1.30, 95% CI 1.11 to 1.53). Conclusions: MTX, TNF antagonists and prednisone at doses &gt;10 mg daily were associated with increased risks of overall infections. Low-dose prednisone and TNF antagonists (but not MTX) increased the risk of opportunistic infections.
Ionophore and Arachidonic Acid Stimulation of Airway Responses in Rhesus Monkeys
Authors: Roy Patterson, Kathleen E. Harris, Paul A. Greenberger
Journal: Journal of Clinical Investigation (1979)

Aerosolized doses of the ionophore, A23187, and arachidonic acid individually resulted in no airway response in rhesus monkeys. When these two agents were given simultaneously, by aerosol, an airway response occurred. The pulmonary function abnormalities that occurred qualitatively simulated those of an antigen-induced airway response. This is the first demonstration in our laboratory of two agents which singly will not produce a response but which are reactive when delivered in combination. Other fatty acids did not produce a similar response. The response to A23187 and arachidonic acid occurred only in rhesus monkeys from our colony which had been demonstrated to have airway responses to aerosolized antigen challenge, a response shown previously to be associated with hyperreactive airways to pharmacologic stimuli. The A23187 and arachidonic acid response was inhibited by aerosolized 5,8,11,14-eicosatetraynoic acid, an inhibitor of the cyclooxygenase and lipoxygenase pathways of arachidonic acid metabolism. Further, indomethacin, a prostaglandin synthetase inhibitor of the cyclooxygenase pathway, inhibited the response, although previous studies showed that this drug will potentiate an antigen-induced response in this animal model of asthma. The slow-reacting substance of anaphylaxis antagonist, FPL 55712, did not inhibit the A23187-arachidonic acid response under the conditions of these experiments. The mechanism of the A23187-arachidonic acid airway response in rhesus monkeys may or may not be the same as the antigen-induced response.
Folic Acid Supplements in Pregnancy and Severe Language Delay in Children
Authors: Christine Roth, Per Magnus, Synnve Schjølberg, Camilla Stoltenberg, Pål Surén, Ian W. McKeague, George Davey Smith, Ted Reichborn-Kjennerud, Ezra Susser
Journal: JAMA (2011)

<h3>Context</h3>Prenatal folic acid supplements reduce the risk of neural tube defects and may have beneficial effects on other aspects of neurodevelopment.<h3>Objective</h3>To examine associations between mothers' use of prenatal folic acid supplements and risk of severe language delay in their children at age 3 years.<h3>Design, Setting, and Patients</h3>The prospective observational Norwegian Mother and Child Cohort Study recruited pregnant women between 1999 and December 2008. Data on children born before 2008 whose mothers returned the 3-year follow-up questionnaire by June 16, 2010, were used. Maternal use of folic acid supplements within the interval from 4 weeks before to 8 weeks after conception was the exposure. Relative risks were approximated by estimating odds ratios (ORs) with 95% CIs in a logistic regression analysis.<h3>Main Outcome Measure</h3>Children's language competency at age 3 years measured by maternal report on a 6-point ordinal language grammar scale. Children with minimal expressive language (only 1-word or unintelligible utterances) were rated as having severe language delay.<h3>Results</h3>Among 38 954 children, 204 (0.5%) had severe language delay. Children whose mothers took no dietary supplements in the specified exposure interval were the reference group (n = 9052 [24.0%], with severe language delay in 81 children [0.9%]). Adjusted ORs for 3 patterns of exposure to maternal dietary supplements were (1) other supplements, but no folic acid (n = 2480 [6.6%], with severe language delay in 22 children [0.9%]; OR, 1.04; 95% CI, 0.62-1.74); (2) folic acid only (n = 7127 [18.9%], with severe language delay in 28 children [0.4%]; OR, 0.55; 95% CI, 0.35-0.86); and (3) folic acid in combination with other supplements (n = 19 005 [50.5%], with severe language delay in 73 children [0.4%]; OR, 0.55; 95% CI, 0.39-0.78).<h3>Conclusion</h3>Among this Norwegian cohort of mothers and children, maternal use of folic acid supplements in early pregnancy was associated with a reduced risk of severe language delay in children at age 3 years.
Physical Activity of Moderate Intensity and Risk of Type 2 Diabetes
Authors: Christie Y. Jeon, R. Peter Lokken, Frank B. Hu, Rob M. van Dam
Journal: Diabetes Care (2007)

To systematically evaluate the evidence for an association between physical activity of moderate intensity and risk of type 2 diabetes.We searched EMBASE and Medline through March 2006 and examined reference lists of retrieved articles. We excluded studies that did not assess physical activity of moderate intensity independent of activities of vigorous intensity (more than six times the resting metabolic rate). Information on study design, participant characteristics, assessment of physical activity, and outcomes and estimates of associations were extracted independently by two investigators. We calculated summary relative risks (RRs) using a random-effects model for the highest versus the lowest reported duration of activities.We identified 10 prospective cohort studies of physical activity of moderate intensity and type 2 diabetes, including a total of 301,221 participants and 9,367 incident cases. Five of these studies specifically investigated the role of walking. The summary RR of type 2 diabetes was 0.69 (95% CI 0.58-0.83) for regular participation in physical activity of moderate intensity as compared with being sedentary. Similarly, the RR was 0.70 (0.58-0.84) for regular walking (typically > or = 2.5 h/week brisk walking) as compared with almost no walking. The associations remained significant after adjustment for BMI. Similar associations were observed in men and women and in the U.S. and Europe.These findings indicate that adherence to recommendations to participate in physical activities of moderate intensity such as brisk walking can substantially reduce the risk of type 2 diabetes.