tbuckley/cabot-search huggingface dataset:
Cluster analyses in a sample of COPD patients
Authors: Stephania Margotto, Laura Caram, Suzana Tanni, Renata Ferrari, André Bertani, Thaís Garcia, Sérgio Paiva, Irma Godoy
Journal: European Respiratory Journal (2014)

Defining phenotype of COPD patients has been necessary to optimize pharmacological treatment and recognize mortality risk factors. The aim of this study was to identify clusters in a sample of 166 COPD patients (GOLD stage: I:31, II:58, III:30, IV:47). All individuals underwent to medical history and physical examination, clinical and laboratory assessments and pre-and post-bronchodilator spirometry. Comorbidities were registered based on medical chart diagnoses and clinical evaluation and the burden classified according to Charlson index. Arterial blood gases, inflammatory mediators, exercise capacity (six minute walk distance-6MWD) and quality of life (St. George9s Respiratory Questionnaire - SGRQ) were evaluated. All statistical analyses were performed using Viscovery Profiler 5.3 by Viscovery Software GmbH (www.viscovery.net;Vienna,Austria). The variables included in the analyses were: Charlson index, smoking history, 6MWD, SGRQ scores (impact, symptoms and activity), baseline dyspnea index (BDI), PaO 2 , PaCO 2 , FEV 1 , hematocrit, lymphocytes, albumin, interleukin 6 (IL6) and C-reactive protein (CRP), glycemia, triglycerides, LDL, HDL and body mass index (BMI). We identified six different clusters. C1: comorbidity [SGRQ impact score, Charlson index] 36.31%, C2: quality of life impairment [SGRQ activity, impact, symptoms scores] 23.81%, C3: metabolic profile [LDL, triglycerides and 6MWD] 16.07%, C4: severe COPD [BDI, FEV 1 , PaO 2 , SGRQ activity score and 6MWD] 9.52%, C5: inflammatory systemic [IL6 and 6MWD] 10.12% and C6: obstructive sleep apnea [glycemia, BMI and PaCO 2 ] 4.17%. In conclusion, the findings show that COPD patients can be classified in different clusters that could interfere in the management and outcomes during follow-up.
Liver stiffness in nonalcoholic fatty liver disease: A comparison of supersonic shear imaging, FibroScan, and ARFI with liver biopsy
Authors: Christophe Cassinotto, Jérome Boursier, Victor de Lédinghen, Jérome Lebigot, Bruno Lapuyade, Paul Cales, Jean‐Baptiste Hiriart, Sophie Michalak, Brigitte Le Bail, Victoire Cartier, Amaury Mouries, Frédéric Oberti, Isabelle Fouchard‐Hubert, Julien Vergniol, Christophe Aubé
Journal: Hepatology (2015)

Nonalcoholic fatty liver disease (NAFLD) has become a major public health issue. The goal of this study was to assess the clinical use of liver stiffness measurement (LSM) evaluated by supersonic shear imaging (SSI), FibroScan, and acoustic radiation force impulse (ARFI) in a cohort of NAFLD patients who underwent liver biopsy. A total of 291 NAFLD patients were prospectively enrolled from November 2011 to February 2015 at 2 French university hospitals. LSM was assessed by SSI, FibroScan (M probe), and ARFI within two weeks prior to liver biopsy. Calculations of the area under the receiver operating curve (AUROC) were performed and compared for the staging of liver fibrosis. AUROC for SSI, FibroScan, and ARFI were 0.86, 0.82, and 0.77 for diagnoses of ≥F2; 0.89, 0.86, and 0.84 for ≥F3; and 0.88, 0.87, and 0.84 for F4, respectively. SSI had a higher accuracy than ARFI for diagnoses of significant fibrosis (≥F2) (P = 0.004). Clinical factors related to obesity such as body mass index ≥ 30 kg/m(2) , waist circumference ≥102 cm or increased parietal wall thickness were associated with LSM failures when using SSI or FibroScan and with unreliable results when using ARFI. In univariate analysis, FibroScan values were slightly correlated with NAFLD activity score and steatosis (R = 0.28 and 0.22, respectively), whereas SSI and ARFI were not; however, these components of NAFLD did not affect LSM results in multivariate analysis. The cutoff values for SSI and FibroScan for staging fibrosis with a sensitivity ≥90% were very close: 6.3/6.2 kPa for ≥F2, 8.3/8.2 kPa for ≥F3, and 10.5/9.5 kPa for F4.Although obesity is associated with an increase in LSM failure, the studied techniques and especially SSI provide high value for the diagnosis of liver fibrosis in NAFLD patients. (Hepatology 2016;63:1817-1827).
Collaborative Modeling of the Benefits and Harms Associated With Different U.S. Breast Cancer Screening Strategies
Authors: Jeanne S. Mandelblatt, Natasha K. Stout, Clyde B. Schechter, Jeroen J. van den Broek, Diana L. Miglioretti, Martin Krapcho, Amy Trentham-Dietz, Diego Munoz, Sandra J. Lee, Donald A. Berry, Nicolien T. van Ravesteyn, Oguzhan Alagoz, Karla Kerlikowske, Anna N.A. Tosteson, Aimee M. Near, Amanda Hoeffken, Yaojen Chang, Eveline A. Heijnsdijk, Gary Chisholm, Xuelin Huang, Hui Huang, Mehmet Ali Ergun, Ronald Gangnon, Brian L. Sprague, Sylvia Plevritis, Eric Feuer, Harry J. de Koning, Kathleen A. Cronin
Journal: Annals of Internal Medicine (2016)

Background: Controversy persists about optimal mammography screening strategies. Objective: To evaluate screening outcomes, taking into account advances in mammography and treatment of breast cancer. Design: Collaboration of 6 simulation models using national data on incidence, digital mammography performance, treatment effects, and other-cause mortality. Setting: United States. Patients: Average-risk U.S. female population and subgroups with varying risk, breast density, or comorbidity. Intervention: Eight strategies differing by age at which screening starts (40, 45, or 50 years) and screening interval (annual, biennial, and hybrid [annual for women in their 40s and biennial thereafter]). All strategies assumed 100% adherence and stopped at age 74 years. Measurements: Benefits (breast cancer–specific mortality reduction, breast cancer deaths averted, life-years, and quality-adjusted life-years); number of mammograms used; harms (false-positive results, benign biopsies, and overdiagnosis); and ratios of harms (or use) and benefits (efficiency) per 1000 screens. Results: Biennial strategies were consistently the most efficient for average-risk women. Biennial screening from age 50 to 74 years avoided a median of 7 breast cancer deaths versus no screening; annual screening from age 40 to 74 years avoided an additional 3 deaths, but yielded 1988 more false-positive results and 11 more overdiagnoses per 1000 women screened. Annual screening from age 50 to 74 years was inefficient (similar benefits, but more harms than other strategies). For groups with a 2- to 4-fold increased risk, annual screening from age 40 years had similar harms and benefits as screening average-risk women biennially from 50 to 74 years. For groups with moderate or severe comorbidity, screening could stop at age 66 to 68 years. Limitation: Other imaging technologies, polygenic risk, and nonadherence were not considered. Conclusion: Biennial screening for breast cancer is efficient for average-risk populations. Decisions about starting ages and intervals will depend on population characteristics and the decision makers' weight given to the harms and benefits of screening. Primary Funding Source: National Institutes of Health.
The NEDD8 Conjugation Pathway Inhibitor MLN4924 Activates AMPK and Induces The ER Stress/UPR-Mediated Cell Death Pathway In Acute Lymphoblastic Leukemia
Authors: Gilles M. Leclerc, Shuhua Zheng, Ronan T. Swords, Guy J. Leclerc, Julio C. Barredo
Journal: Blood (2013)
Abstract 16343: Normal Values and Age Related Changes of Left and Right Atrial Phasic Functions by Speckle Tracking Echocardiography
Authors: Roxana Cristina G Rimbas, Simona Ionela Calin, Oana Aurelia Enescu, Sorina Mihaila, Dragos Vinereanu
Journal: Circulation (2014)

Introduction: Limited data are reported about age related changes of LA and RA functions, and interatrial relationship. Methods: 131 normal subjects (19-78 yrs, 89 women), divided in 4 age groups, were studied by conventional and speckle tracking echo (STE). LA and RA volumes were measured: pre atrial contraction (Vp), minimal (Vmin), and maximal (Vmax), and computed to define atrial ejection fractions: active EF = (Vp-Vmin)/Vp; expansion index EI = (Vmax-Vmin)/Vmin; passive EF = (Vmax-Vp)/Vmax. Active function was assessed from negative strain at atrial contraction (GSA-) and time from P onset to peak (TGSA-), and late diastolic strain rate (GSRL); passive function from positive global strain (GSA+) and time from R to peak (TGSA+), and from early negative diastolic SR (GSRE); reservoir function from the sum of GSA- and GSA+ (SUMGSA), positive global SR at the beginning of ventricular systole (GSR+) and derived time from P onset (TGSR+). We defined for LA a maximal difference (DIF) of all derived times, as a measurement of LA synchrony, and also a difference between RA times and maximal correspondent LA times, as an interatrial synchrony. Results: All LAEFs, Vmin, and Vp decreased over 50 yrs, and Vmax over 60 yrs. RA reservoir function decreased over 60 yrs, while passive RA function over 50 yrs. Active LA function (GSRL) decreased over 60 yrs. LA reservoir and conduit function decreased over 50 yrs. All derived times were increased over 40 yrs. LA and also interatrial contraction and relaxation synchrony were altered only after 60 yrs (all p&lt;0.001) (Tables). Correspondent RA and LA functions are significantly correlated, irrespective of age (r=0.6, p&lt;0.001). Conclusion: Although LA and RA functions are strongly correlated, they have different age related changes. RA volumes, EFs, and active function were not affected by age, whereas LAEFs, volumes, passive and reservoir LA and RA functions decreased over 50 yrs. LA and also interatrial synchrony were altered after 60 yrs.
Selective Targeting of a Novel Epsin–VEGFR2 Interaction Promotes VEGF-Mediated Angiogenesis
Authors: H.N. Ashiqur Rahman, Hao Wu, Yunzhou Dong, Satish Pasula, Aiyun Wen, Ye Sun, Megan L. Brophy, Kandice L. Tessneer, Xiaofeng Cai, John McManus, Baojun Chang, Sukyoung Kwak, Negar S. Rahman, Wenjia Xu, Conrad Fernandes, John Michael Mcdaniel, Lijun Xia, Lois Smith, R. Sathish Srinivasan, Hong Chen
Journal: Circulation Research (2016)

Rationale : We previously reported that vascular endothelial growth factor (VEGF)-induced binding of VEGF receptor 2 (VEGFR2) to epsins 1 and 2 triggers VEGFR2 degradation and attenuates VEGF signaling. The epsin ubiquitin interacting motif (UIM) was shown to be required for the interaction with VEGFR2. However, the molecular determinants that govern how epsin specifically interacts with and regulates VEGFR2 were unknown. Objective : The goals for the present study were as follows: (1) to identify critical molecular determinants that drive the specificity of the epsin and VEGFR2 interaction and (2) to ascertain whether such determinants were critical for physiological angiogenesis in vivo. Methods and Results : Structural modeling uncovered 2 novel binding surfaces within VEGFR2 that mediate specific interactions with epsin UIM. Three glutamic acid residues in epsin UIM were found to interact with residues in VEGFR2. Furthermore, we found that the VEGF-induced VEGFR2–epsin interaction promoted casitas B-lineage lymphoma–mediated ubiquitination of epsin, and uncovered a previously unappreciated ubiquitin-binding surface within VEGFR2. Mutational analysis revealed that the VEGFR2–epsin interaction is supported by VEGFR2 interacting specifically with the UIM and with ubiquitinated epsin. An epsin UIM peptide, but not a mutant UIM peptide, potentiated endothelial cell proliferation, migration and angiogenic properties in vitro, increased postnatal retinal angiogenesis, and enhanced VEGF-induced physiological angiogenesis and wound healing. Conclusions : Distinct residues in the epsin UIM and VEGFR2 mediate specific interactions between epsin and VEGFR2, in addition to UIM recognition of ubiquitin moieties on VEGFR2. These novel interactions are critical for pathophysiological angiogenesis, suggesting that these sites could be selectively targeted by therapeutics to modulate angiogenesis.
SYDNEY E. SALMON, MD
Authors: Raymond Alexanian, Kenneth Anderson, Bart Barlogie, James Berenson, William S. Dalton, Robert A. Kyle
Journal: Journal of Clinical Oncology (2000)

Article Tools IN MEMORIAM Article Tools OPTIONS & TOOLS Export Citation Track Citation Add To Favorites Rights & Permissions COMPANION ARTICLES No companion articles ARTICLE CITATION DOI: 10.1200/JCO.2000.18.1.1 Journal of Clinical Oncology - published online before print September 21, 2016 SYDNEY E. SALMON, MD , Raymond AlexanianxRaymond AlexanianSearch for articles by this author , Kenneth AndersonxKenneth AndersonSearch for articles by this author , Bart BarlogiexBart BarlogieSearch for articles by this author , James BerensonxJames BerensonSearch for articles by this author , William S. DaltonxWilliam S. DaltonSearch for articles by this author , Robert A. KylexRobert A. KyleSearch for articles by this author Show More University of Texas M.D. Anderson Cancer Center, Houston, TXDana-Farber Cancer Institute, Boston, MA Arkansas Cancer Research Center University of Arkansas for Medical Sciences, Little Rock, AR University of California at Los Angeles, Los Angeles, CAH. Lee Moffitt Cancer Center, Tampa, FL Mayo Clinic, Rochester, MN https://doi.org/10.1200/JCO.2000.18.1.1 Full Text PDF Figures and Tables "SYDNEY E. SALMON, MD." Journal of Clinical Oncology, 18(1), p. 1© 2000 by American Society of Clinical Oncology
Sexual misconduct by psychiatrists: the ethical and clinical dilemma of confidentiality
Authors: A A Stone
Journal: American Journal of Psychiatry (1983)

Psychiatrists have an ethical obligation to expose colleagues who sexually abuse their patients. However, this obligation often conflicts with the ethical obligation of confidentiality. The principled ethical dilemma is grounded in practical clinical considerations. The author suggests systematic use of consultation as a potential method to address both ethical and clinical responsibilities.
A randomized trial of anthracycline dose intensification during induction of younger patients with acute myeloid leukemia: Results of Eastern Cooperative Oncology Group study E1900
Authors: H. F. Fernandez, Z. Sun, M. R. Litzow, S. M. Luger, E. M. Paietta, G. Dewald, R. P. Ketterling, J. M. Rowe, H. M. Lazarus, M. S. Tallman
Journal: Journal of Clinical Oncology (2009)

7003 Background: In younger adults with newly diagnosed acute myeloid leukemia (AML), anthracycline dose intensification during induction may improve complete remission (CR) rates; however, an improvement in overall survival (OS) in a randomized trial has not been demonstrated. This unresolved issue led the ECOG to compare standard dose (SDD) to high-dose daunorubicin (HDD) in induction. Methods: Adult patients with previously untreated AML were randomized to receive either SDD (45 mg/m 2 /d) or HDD (90 mg/m 2 /d) each for 3days combined with standard-dose cytarabine (100 mg/m 2 /d) for 7 days by continuous intravenous infusion. Those achieving a CR were allocated to allogeneic hematopoietic stem cell transplantation (HSCT) or high-dose cytarabine (with or without a single dose of gemtuzumab ozogamicin) prior to autologous HSCT. Intravenous busulfan and cyclophosphamide was the preparative regimen for both allogeneic and autologous HSCT. The primary end point of this study was OS from the time of induction randomization. Results: 633 patients, age 18 to 60 (median 48) years, were entered in this study. There were no differences in patient demographics or disease characteristics between the two groups at presentation. In an intention-to-treat analysis, HDD resulted in a significantly higher CR rate (63.3% vs. 47.7%, p = 0.0003) than SDD. Induction deaths were similar between the two groups (5.4 vs. 5.0%, p = ns). 334 (52.8%) patients entered the consolidation phase. 57.4% of HDD and 48.1% of the SDD patients, received consolidation therapy on study, and 28.7% and 23.1% proceeded to HSCT respectively. Median OS was superior for the HDD (23.7 months) over the SDD (15.1 months) group (p = 0.005). In subgroup analysis, patients with favorable or intermediate-risk cytogenetics or age &lt;55 years benefited from the HDD. Conclusions: We demonstrate for the first time in a prospective randomized trial that intensifying induction therapy through a higher daily anthracycline dose, in the setting of identical intensive consolidation therapy, results in a higher CR rate as well as prolonged OS. In younger AML patients a higher dose of anthracycline in induction should be considered the new standard of care. No significant financial relationships to disclose.
Japan to test a million cattle after discovery of first case of BSE
Authors: Joe Lamar
Journal: BMJ (2001)

The Japanese government has announced that it will test one million cattle for bovine spongiform encephalopathy (BSE) after the discovery of Asia's first case of mad cow disease. The cows will be tested after they have been slaughtered for meat.

The mass testing, along with a ban on meat and bone feed and the start of new research into Creutzfeldt-Jakob disease, is designed to allay consumers' concerns, which have been heightened by a blundered official response to the discovery.

Brain tissue from a 5 year old Holstein dairy cow from a farm in Chiba, just outside Tokyo, tested positive for the disease in late August. The government says it will not confirm that the cow was infected until a further examination is carried out in Britain, but several nations, including the United States, South Korea, Malaysia, and Taiwan, have already banned Japanese beef.
Benefit of Atrasentan in Men with Hormone Refractory Prostate Cancer Metastatic to Bone
Authors: A. Lipton, D. J. Sleep, S. M. Hulting, J. D. Isaacson, A. R. Allen
Journal: Journal of Clinical Oncology (2004)

4687 Background: Bone alkaline phosphatase (BAP) predicts time to progression (TTP) and survival in patients with hormone refractory prostate cancer (HRPC). We tested 2 hypotheses: a) BAP at baseline is predictive of both TTP and survival in HRPC patients with bony metastases only and b) BAP predicts response to atrasentan therapy in these men. Methods: Data were analyzed from 474 men with HRPC metastastic only to bone from a randomized, double-blind, placebo-controlled phase 3 trial of atrasentan 10 mg QD. Kaplan-Meier and Cox proportional hazard methodologies were used to compare TTP (a composite of radiological and clinical outcomes) between treatments. Values from 451 patients with baseline BAP values were analyzed. Data from treatment arms were pooled and stratified by baseline BAP < and >/= the median value. TTP and survival and the effect of treatment within the 2 groups were compared using Kaplan-Meier methodology. Results: 253 patients received atrasentan, 221 received placebo; atrasentan resulted in a significant delay in TTP versus placebo (p=0.026). The median baseline BAP value was 31.5 ng/mL. Median TTP for patients whose baseline BAP < median was 168 days versus 85 days for patients with baseline BAP >/= median (p<0.001) and median time to death was 741 days vs 461 days for patients with BAP < median and >/= median, respectively (p<0.001). In patients with a baseline BAP >/= median, atrasentan significantly delayed TTP versus placebo, while in patients with baseline BAP < median, treatment effect did not reach significance (table). Conclusions: These data confirm that high baseline BAP is predictive of early disease progression and reduced survival in HRPC patients with only bone metastases, independent of therapy. Atrasentan therapy significantly delayed TTP versus placebo in subjects with bone metastases only. It also significantly increased TTP in bony metastatic HRPC patients with a high baseline BAP. Author Disclosure Employment or Leadership Consultant or Advisory Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Abbott Laboratories Abbott Laboratories
Synergistic growth inhibition of RCC and NSCLC cell lines by sorafenib plus vorinostat and induction of angiogenic genes by ER stress
Authors: H. A. Drabkin, G. Sharma, L. J. Costa, C. Korch, R. M. Gemmill
Journal: Journal of Clinical Oncology (2009)

e16114 Sorafenib, vorinostat and the combination were examined in 34 RCC and NSCLC cell lines. In growth assays, sorafenib at 8 μM resulted in synergy with multiple vorinostat doses, whereas no synergy was seen with lower doses. Changes in phospho-ERK and AKT were not predictive of growth inhibition, whereas frequent inhibition of cyclin D1 and upregulation of p21 Waf1 was observed. To anticipate resistance mechanisms to the anti-angiogenic effects of sorafenib, we studied the expression of 13 angiogenic factors in 10 selected lines. At baseline, bFGF, VEGF and IL-8 were highly expressed in RCCs, whereas Gro-α, VEGF, and IL-8 predominated in NSCLCs. Multiple angiogenic factors were upregulated by sorafenib and vorinostat, especially VEGF, IL-6, CTGF, EDN1, PDGFβ, and IL-8. Importantly, sorafenib at 8 μM, but not lower doses, induced ER stress in these cell lines and thapsigargin or tunicamycin treatment recapitulated many, but not all, of the observed angiogenic gene responses to sorafenib. In fact, CHOP induction by sorafenib plus vorinostat was the only parameter, other than growth inhibition, that changed in a synergistic manner. In summary, sorafenib plus vorinostat potently inhibits the in vitro growth of RCC and NSCLC cell lines. Upregulation of multiple angiogenic genes, in part by an ER-stress mechanism, may contribute to acquired resistance in vivo. No significant financial relationships to disclose.
Large-Effect Beneficial Synonymous Mutations Mediate Rapid and Parallel Adaptation in a Bacterium
Authors: Deepa Agashe, Mrudula Sane, Kruttika Phalnikar, Gaurav D. Diwan, Alefiyah Habibullah, Norma Cecilia Martinez-Gomez, Vinaya Sahasrabuddhe, William Polachek, Jue Wang, Lon M. Chubiz, Christopher J. Marx
Journal: Molecular Biology and Evolution (2016)

Contrary to previous understanding, recent evidence indicates that synonymous codon changes may sometimes face strong selection. However, it remains difficult to generalize the nature, strength, and mechanism(s) of such selection. Previously, we showed that synonymous variants of a key enzyme-coding gene (fae) of Methylobacterium extorquens AM1 decreased enzyme production and reduced fitness dramatically. We now show that during laboratory evolution, these variants rapidly regained fitness via parallel yet variant-specific, highly beneficial point mutations in the N-terminal region of fae. These mutations (including four synonymous mutations) had weak but consistently positive impacts on transcript levels, enzyme production, or enzyme activity. However, none of the proposed mechanisms (including internal ribosome pause sites or mRNA structure) predicted the fitness impact of evolved or additional, engineered point mutations. This study shows that synonymous mutations can be fixed through strong positive selection, but the mechanism for their benefit varies depending on the local sequence context.
Evidence by Cellular Mosaicism for Monoclonal Metastasis of Spontaneous Mouse Mammary Tumors&lt;xref ref-type="fn" rid="FN2"&gt;2&lt;/xref&gt;&lt;xref ref-type="fn" rid="FN3"&gt;3&lt;/xref&gt;
Authors: A Ootsuyama, K Tanaka, H Tanooka
Journal: JNCI Journal of the National Cancer Institute (1987)

Female (SHN × C3H/He)F1 mice carrying spontaneous mammary tumors with cellular mosaicism with respect to isozymes of phosphoglycerate kinase (PGK) showed a high incidence of lung metastases. On resection of successively appearing mammary tumors, mice survived a maximum of 8 tumors. In these mice with multiple primary mammary tumors and multiple metastases, not only each individual metastasis but also alt the metastases in the same lung had the same pattern of PGK isozymes and the same histologic type in the PGK-mosaic background of the host, indicating the monoclonal origin of these metastases. In several cases, this single pattern of metastatic colonies coincided with that of only one of several primary tumors, indicating that this tumor had metastasized. In these cases, these tumors were not necessarily the earliest of the primary tumors, and they were not located in any particular site.