tbuckley/cabot-search huggingface dataset:
Analysis of Clonal Contributions to T Lymphoid and Myeloid Lineages during Early Hematopoiesis Following Autologous Transplantation in the Rhesus Macaque.
Authors: Rima L. Adler, Peiman Hematti, Boris Calmels, Cole J. Ferguson, Keyvan Keyvanfar, Colin Wu, Dean Follmann, Cynthia E. Dunbar
Journal: Blood (2004)
Primary Stroke Center Hospitalization for Elderly Patients With Stroke
Authors: Kimon Bekelis, Nancy J. Marth, Kendrew Wong, Weiping Zhou, John D. Birkmeyer, Jonathan Skinner
Journal: JAMA Internal Medicine (2016)

<h3>Importance</h3> Physicians often must decide whether to treat patients with acute stroke locally or refer them to a more distant Primary Stroke Center (PSC). There is little evidence on how much the increased risk of prolonged travel time offsets benefits of a specialized PSC care. <h3>Objectives</h3> To examine the association of case fatality with receiving care in PSCs vs other hospitals for patients with stroke and to identify whether prolonged travel time offsets the effect of PSCs. <h3>Design, Setting, and Participants</h3> Retrospective cohort study of Medicare beneficiaries with stroke admitted to a hospital between January 1, 2010, and December 31, 2013. Drive times were calculated based on zip code centroids and street-level road network data. We used an instrumental variable analysis based on the differential travel time to PSCs to control for unmeasured confounding. The setting was a 100% sample of Medicare fee-for-service claims. <h3>Exposures</h3> Admission to a PSC. <h3>Main Outcomes and Measures</h3> Seven-day and 30-day postadmission case-fatality rates. <h3>Results</h3> Among 865 184 elderly patients with stroke (mean age, 78.9 years; 55.5% female), 53.9% were treated in PSCs. We found that admission to PSCs was associated with 1.8% (95% CI, −2.1% to −1.4%) lower 7-day and 1.8% (95% CI, −2.3% to −1.4%) lower 30-day case fatality. Fifty-six patients with stroke needed to be treated in PSCs to save one life at 30 days. Receiving treatment in PSCs was associated with a 30-day survival benefit for patients traveling less than 90 minutes, but traveling at least 90 minutes offset any benefit of PSC care. <h3>Conclusions and Relevance</h3> Hospitalization of patients with stroke in PSCs was associated with decreased 7-day and 30-day case fatality compared with noncertified hospitals. Traveling at least 90 minutes to receive care offset the 30-day survival benefit of PSC admission.
Re: Halford et al.: Detailed phenotypic and genotypic characterization of Bietti crystalline dystrophy (Ophthalmology 2014;121:1174-84) reply
Authors: S Halford, G Liew, D S Mackay, P I Sergouniotis, R Holt, S Broadgate, E V Volpi, L Ocaka, A G Robson, G E Holder, A T Moore, M Michaelides, A R Webster
Journal: Ophthalmology (2015)
Abstract LB-157: Chromatin alterations induce C-MYC and BRD4 downregulation in pediatric sarcoma
Authors: Elodie Da Costa, Gregory Armaos, Simon Jacques-Ricard, Annie Beaudry, Noël Raynal.
Journal: Cancer Research (2016)

Abstract Sarcoma accounts for 15% of all pediatric cancers diagnosed every year. Refractory patients have a poor prognosis with a 5-year survival rate of 10%, demonstrating the need for development of new therapeutic approaches. Epigenetic events, including DNA methylation and post-translational histone modifications (such as histone acetylation), are responsible for silencing tumor suppressor genes and overexpressing oncogenes. In sarcomas, a better understanding of epigenetic alterations is needed to develop new epigenetic targeted therapies. Several epigenetics drugs have demonstrated anticancer activity against sarcoma cell lines but the identification of a specific target is still missing. We demonstrated that targeting histone acetylation may represent a specific epigenetic mark in pediatric sarcomas. We identified that proscillaridin A, a newly defined epigenetic drug, has epigenetic and anticancer effects on osteosarcoma (U2OS) and rhabdomyosarcoma (RD) cell lines. Our findings show a decrease of histone 3 acetylation on specific lysine residues after a 48h-treatment with proscillaridin A at 5 nM, a clinically relevant dose. These effects correlate with downregulation of histone acetylation associated proteins such as bromodomain BRD4 and oncogene C-MYC. A 48h-treatment with proscillaridin A produces a G2/M block and a reduction in the clonogenic potential of both U2OS and RD cells with IC50 value of approximately 6 nM. Interestingly, remaining colonies of RD cells fully lost their abilities to growth after drug removal, suggesting a long-term epigenetic reprograming. We demonstrated that proscillaridin A epigenetic effects occurred through calcium signaling since its mechanism of action may be dependent on calcium-calmodulin kinase activity.These promising results illustrate the epigenetic and anticancer potential of proscillaridin A against pediatric sarcoma. Additional experiments are currently ongoing in order to further characterize the mechanism of action of proscillaridin A in vitro and in vivo. Citation Format: Elodie Da Costa, Gregory Armaos, Simon Jacques-Ricard, Annie Beaudry, Noël Raynal. Chromatin alterations induce C-MYC and BRD4 downregulation in pediatric sarcoma. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr LB-157.
Epidemiology, risk factors, and outcomes of invasive fungal infection in adults with acute myelogenous leukemia undergoing intensive induction chemotherapy.
Authors: K. Lu, D. Neofytos, A. Blackford, A. H. Seung, J. E. Karp
Journal: Journal of Clinical Oncology (2010)

6579 Background: The epidemiology and outcomes of invasive fungal infections (IFI) in patients with acute myelogenous leukemia (AML) have been poorly described. Methods: We performed a single center, retrospective analysis of the epidemiology, risk factors and clinical outcomes of IFIs in newly-diagnosed AML patients undergoing intensive, multi-agent induction timed sequential therapy (TST). Patients did not receive antifungal prophylaxis. IFIs were defined using EORTC/MSG criteria. Results: Of 97 consecutive patients (58% male; median age 53, range 22-72) admitted in 2007 and 2008, 27 (28%) had IFI, of which 7 (26%) were proven, 1 (4%) probable, and 17 (68%) possible with lung CT findings characteristic of fungal (mold) pneumonia. Of 8 proven/probable cases, 4 were due to molds and 4 were due to yeasts. Of 91 (94%) receiving antifungal therapy beginning median day 7 (range day -14 through day 25) of AML treatment; 41 (42%) received monotherapy (66% liposomal amphotericin B, 34% voriconazole) and the rest received multiple antifungals. Using univariate analysis, we identified risk factors for IFIs (Table 1). Occurrence of IFI was associated with lower complete remission rate (52% vs. 70% -IFI, p=0.06) and a decrease in 6 month survival (58% vs. 85% -IFI, p=0.01). Conclusions: AML patients with IFIs are more likely to die within 6 months of beginning intensive induction TST. Through this analysis, we are able to identify risk factors that may be associated with development of IFIs. Such identification may help to develop effective preventive antifungal strategies for high risk AML patients. Risk factors for + IFI cohort (overall), and for IFIs due to yeasts and molds No IFI (N=70) IFI (N=27) P- value IFI- yeasts (N=4) P-value IFI-moulds (N=23) P-value Age > 50 years (%) 49 70 0.07 75 NS 70 0.09 Presenting blast count > 10,000 (%) 26 44 0.09 50 NS 43 0.12 Time to ANC < 100 cells/mm3* 7 5 0.08 4 0.16 5 0.16 Time to recovery of ANC >100 cells/mm3* 22.5 26 0.07 25 NS 27 0.12 Onset of mucositis** 14 11.5 0.03 8.5 0.14 12 0.06 Duration of parenteral nutrition* 10 15 0.04 15 NS 14.5 0.07 NS: Non significant, ANC: Absolute neutrophil count. * Median Days of AML therapy (begins on Day 1) No significant financial relationships to disclose.
BETA-3-ADRENOCEPTOR-AGONISTS LEAD TO INTRAHEPATIC VASODILATION VIA GS/CAMP STIMULATION AND DECREASED RHO-KINASE ACTIVITY IN LIVER CIRRHOSIS
Authors: Jonel Trebicka, Martin Hennenberg, Michaela Granzow, Sabine Klein, Wim Laleman, Frederik Nevens, Johan Zaagsma, Joerg Heller, Tilman Sauerbruch
Journal: Hepatology (2009)
Interleukin-6 Promoter and Receptor Polymorphisms, Body Mass Index and Risk of Multiple Myeloma.
Authors: Wendy Cozen, Mulugeta Gebregziabher, David Vandenberg, David Conti, Gerhard Coetzee, Leslie Bernstein, Sophia S. Wang, Nathaniel Rothman, Patricia Hartge, Wei Wang, Simon Coetzee, Sue Ann Ingles
Journal: Blood (2005)
Abstract 16058: Comparing Symptoms and Quality of Life in Women and Men with Atrial Fibrillation: Results from the Orbit-AF Registry
Authors: Jonathan P Piccini, DaJuanicia N Holmes, Laine Thomas, Larry A Allen, Gregg C Fonarow, Bernard J Gersh, Peter R Kowey, James A Reiffel, Gerald V Naccarelli, Paul Chang, Paul S Chan, John A Spertus, Eric D Peterson
Journal: Circulation (2012)

Background: Reducing symptoms and improving quality of life (QoL) are important treatment goals in atrial fibrillation (AF). Yet little is known about how patient-reported QoL differs between women...
An outbreak of a possibly new Salmonella enterica subspecies enterica serovar with the antigenic formula 11:z41:e,n,z15, Greece, March to May 2016: preliminary results
Authors: Georgia Mandilara, Kassiani Mellou, Kleon Karadimas, Leonidas Georgalis, Michalis Polemis, Theano Georgakopoulou, Alkiviades Vatopoulos
Journal: Eurosurveillance (2016)

Eleven Salmonella spp. isolates with the antigenic type 11:z 41 :e,n,z 15 - not referred to in the 9th edition of the White-Kauffman–Le Minor Scheme - were identified at the National Reference Laboratory for Salmonella in Greece. Their pulsed-field gel electrophoresis profiles were indistinguishable. No apparent epidemiological link has yet been identified; the results of a case–case study are pending.
“Nonfunctional” Adrenal Tumors and the Risk for Incident Diabetes and Cardiovascular Outcomes
Authors: Diana Lopez, Miguel Angel Luque-Fernandez, Amy Steele, Gail K. Adler, Alexander Turchin, Anand Vaidya
Journal: Annals of Internal Medicine (2016)

Benign adrenal tumors are commonly discovered on abdominal imaging. Most are classified as nonfunctional and are considered to pose no health risk, but some are considered functional because they secrete hormones that increase risk for metabolic and cardiovascular diseases.To evaluate the hypothesis that nonfunctional adrenal tumors (NFATs) increase risk for cardiometabolic outcomes compared with absence of adrenal tumors.Cohort study.Integrated hospital system.Participants with benign NFATs ("exposed"; n = 166) and those with no adrenal tumor ("unexposed"; n = 740), with at least 3 years of follow-up.Medical records were reviewed from the time of abdominal imaging for development of incident outcomes (hypertension, composite diabetes [prediabetes or type 2 diabetes], hyperlipidemia, cardiovascular events, and chronic kidney disease) (mean, 7.7 years). Primary analyses evaluated independent associations between exposure status and incident outcomes by using adjusted generalized linear models. Secondary analyses evaluated relationships between NFATs and cortisol physiology.Participants with NFATs had significantly higher risk for incident composite diabetes than those without adrenal tumors (30 of 110 [27.3%] vs. 72 of 615 [11.7%] participants; absolute risk, 15.6% [95% CI, 6.9% to 24.3%]; adjusted risk ratio, 1.87 [CI, 1.17 to 2.98]). No significant associations between NFATs and other outcomes were observed. Higher "normal" postdexamethasone cortisol levels (≤50 nmol/L) were associated with larger NFAT size and higher prevalence of type 2 diabetes.Potential bias in the selection of participants and ascertainment of outcomes.Participants with NFATs had a significantly higher risk for diabetes than those without adrenal tumors. These results should prompt a reassessment of whether the classification of benign adrenal tumors as "nonfunctional" adequately reflects the continuum of hormone secretion and metabolic risk they may harbor.National Institutes of Health and Doris Duke Charitable Foundation.
Comprehensive genomic profiling of 295 cases of clinically advanced urothelial carcinoma of the urinary bladder to reveal frequency of clinically relevant genomic alterations.
Authors: Matthew J. Hawryluk, Kai Wang, Siraj Mahamed Ali, Hugh Fisher, Badar Mian, Tipu Nazeer, Julia Andrea Elvin, Juliann Chmielecki, Roman Yelensky, Doron Lipson, Vincent A. Miller, Philip J. Stephens, Jeffrey S. Ross
Journal: Journal of Clinical Oncology (2015)

4526 Background: Clinically advanced metastatic urothelial carcinoma (UC) is a devastating disease lacking effective systemic therapies. Herein, we present a comprehensive genomic profile-based (CGP) study of UC designed to detect clinically relevant genomic alterations (CRGA) that could inform the selection of established and novel targeted therapies. Methods: DNA was extracted from 295 consecutive cases of relapsed/metastatic UC. CGP was performed on hybridization-captured, adaptor ligation based libraries to a mean coverage depth of 688X for 236 cancer-related genes. The CGP assay included base substitutions (SUB), INDELs, copy number alterations (CNA) and fusions/rearrangements. CRGA were defined as GA linked to drugs on the market or under evaluation in mechanism driven clinical trials. Results: There were 75% male and 25% female patients with a mean age of 66 years. 295/295 (100%) of UC were high grade and advanced stage (III and IV). 294/295 (99.7%) UC had at least 1 GA on CGP with a mean of 6.4 GA/UC with 61% SUB + INDEL, 37% CNA and 2% fusions. 275 (93%) UC had at least 1 CRGA involving 75 individual genes with a mean of 2.6 CRGA/UC. The most common CRGA involved CDKN2A (34%), FGFR3 (21%), PIK3CA (20%) and ERBB2 (16%). FGFR3 GA were of diverse type and included 10% fusions. ERBB2 GA were equally divided between amplifications (CNA) and SUB. ERBB2 SUB were predominantly in the extracellular domain and were highly enriched in the micropapillary UC subgroup. Multiple clinical antitumor responses to therapies targeting FGFR3 and ERBB2 will be presented. Conclusions: Using a CGP assay capable of detecting all classes of GA simultaneously, an extraordinary high frequency of CRGA were identified in a large series of patients with clinically advanced UC. More than one-third of these relapsed/refractory cases of UC harbored alterations in FGFR3 and ERBB2 that are showing active responses to targeted therapies. Continued evaluation of CGP for UC and the development of genomic driven clinical trials designed to employ targeted agents potentially in combination with cytotoxic drugs for this challenging disease appears warranted.
Regulation and revalidation of doctors
Journal: BMJ (2006)

Selection bias, however, was discussed in 14 reviews, 10 of which did not report or were unclear about the method of selection of patients.So, though many reviews discussed different types of bias, they did not always provide the information that would enable a reader to assess the risk of bias.In our sample we found the quality of reviews completed for the purpose of clinical guidelines was poor, with worrying implications if these are the reviews guiding clinical practice.Reviews of diagnostic tests would be better carried out separately from the preparation of clinical guidelines. ConclusionsSystematic reviews of diagnostic tests are complex and require reporting of detailed information about the design, conduct, and results of the included primary studies to ensure reviews are useful.We have shown the current poor quality of published reviews and indicated areas for improvement.
ANGIOGENESIS IN BENIGN HUMAN HEPATIC TUMORS A ROLE FOR ANG-1/TIE-2?
Authors: Annette S. Gouw, Wenjiao Zeng, Marijke Buiskool, Inge Platteel, Marius C. van den Heuvel, Sibrand Poppema, Koert P. De Jong, Grietje Molema
Journal: Hepatology (2009)
Alternative Splicing of Titin Restores Diastolic Function in an HFpEF-Like Genetic Murine Model ( <i>Ttn</i> <sup>ΔIAjxn</sup> )
Authors: Mathew Bull, Mei Methawasin, Joshua Strom, Pooja Nair, Kirk Hutchinson, Henk Granzier
Journal: Circulation Research (2016)

Patients with heart failure with preserved ejection fraction (HFpEF) experience elevated filling pressures and reduced ventricular compliance. The splicing factor RNA-binding motif 20 (RBM20) regulates the contour length of titin's spring region and thereby determines the passive stiffness of cardiomyocytes. Inhibition of RBM20 leads to super compliant titin isoforms (N2BAsc) that reduce passive stiffness.To determine the therapeutic potential of upregulating compliant titin isoforms in an HFpEF-like state in the mouse.Constitutive and inducible cardiomyocyte-specific RBM20-inhibited mice were produced on a Ttn(ΔIAjxn) background to assess the effect of upregulating compliant titin at the cellular and organ levels. Genetic deletion of the I-band-A-band junction (IAjxn) in titin increases strain on the spring region and causes a HFpEF-like syndrome in the mouse without pharmacological or surgical intervention. The increased strain represents a mechanical analog of deranged post-translational modification of titin that results in increased passive myocardial stiffness in patients with HFpEF. On inhibition of RBM20 in Ttn(ΔIAjxn) mice, compliant titin isoforms were expressed, diastolic function was normalized, exercise performance was improved, and pathological hypertrophy was attenuated.We report for the first time a benefit from upregulating compliant titin isoforms in a murine model with HFpEF-like symptoms. Constitutive and inducible RBM20 inhibition improves diastolic function resulting in greater tolerance to exercise. No effective therapies exists for treating this pervasive syndrome; therefore, our data on RBM20 inhibition are clinically significant.
Myeloid Cells Exert Immunosuppressive Activity and Have Prognostic Value In Hodgkin Lymphoma
Authors: Alessandra Romano, Nunziatina Parrinello, Calogero Vetro, Piera La Cava, Cesarina Giallongo, Daniele Tibullo, Giovanna Motta, Ugo Consoli, Annalisa Chiarenza, Giuseppe A Palumbo, Francesco Di Raimondo
Journal: Blood (2013)
Trends in the diagnosis and clinical features of melanoma in situ (MIS) in US men and women: A prospective, observational study
Authors: Erin X. Wei, Abrar A. Qureshi, Jiali Han, Tricia Y. Li, Eunyoung Cho, Jennifer Y. Lin, Wen-Qing Li
Journal: Journal of the American Academy of Dermatology (2016)
Abstract 759: Sunitinib has opposite roles to regulate the myeloid-derived suppressor cells in tumors and peripheral blood
Authors: Fang-Hsin Chen, Sheng-Yung Fu, Chun-Chieh Wang, Chi-Shiun Chiang, Ji-Hong Hong
Journal: Cancer Research (2016)

Abstract Recent studies indicate that sunitinib, a tyrosine kinase inhibitor, could decease accumulation of myeloid-derived suppressor cells (MDSC) in tumors and also in peripheral blood. This study aims to investigate the behavior and dynamic profile of myeloid-derived suppressor cells in tumor tissues and peripheral blood of sunitinib-treated mice bearing prostate adenocarcinoma TRAMP-C1 tumors. To this end, 3×106 TRAMP-C1 tumor cells were inoculated at shank muscle of C57BL6/J mouse and sunitinib was administered by intraperitoneal injection of a daily dose of 20mg/kg into mice bearing 4 mm diameter tumor. Comparing to tumors in untreated group, sunitinib administration slightly delayed tumor growth delay for 2 days, but significantly decreased micro-vascular density and induced chronic hypoxia in tumors, resulting in the specific accumulation of CD11b+Gr-1+ MDSCs at the tumor necrotic region within CA-IX positive chronic hypoxic area. Flow cytometry was used to analyze the change of CD11b+ myeloid cells within tumor tissues and peripheral blood. Results showed that sunitinib treatment decreased the percentage of CD11b+Ly6G-LyC- tumor-associated macrophages (TAMs), but increased the percentage of CD11b+Ly6G-Ly6C+ monocytic MDSCs (M-MDSCs) while had no effect on CD11b+Ly6G+Ly6C+ neutrophilic MDSCs (N-MDSCs) within tumor tissues. In contrast, both the percentage of N-MDSCs and M-MDSC were expanded in peripheral blood of sunitinib-treated mice. Multiplex immunoassay showed significant increase of CCL2, CCL3, CCL5, CXCL5, IL-17a, GM-CSF, G-CSF and VEGF-A in tumor tissues, but only CXCL5, IL-á, IL-6 and G-CSF in the peripheral blood of sunitinib-treated mice were affected. In conclusion, this study shows that sunitinib has anti-vascular effect and could disrupt the recruitment of CD11b+Ly6G-Ly6C- TAMs into tumors. We also propose that sunitinib might exert different effects on tumor microenvironment and peripheral blood. Citation Format: Fang-Hsin Chen, Sheng-Yung Fu, Chun-Chieh Wang, Chi-Shiun Chiang, Ji-Hong Hong. Sunitinib has opposite roles to regulate the myeloid-derived suppressor cells in tumors and peripheral blood. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 759.
Abstract 826: Benzyl isothiocyanate inhibits breast cancer-induced osteoclastogenesis
Authors: Subrata K. Pore, Anuradha Sehrawat, Shivendra V. Singh
Journal: Cancer Research (2016)

Abstract Breast cancer is a major public health issue for women worldwide and 70% of the disease preferentially metastasizes to bone resulting in its destruction. Advanced breast cancer releases osteoclastogenic factors to promote bone resorption. As bone metastasis with breast cancer is associated with high mortality, osteoclastogenesis is a potential therapeutic target. We have shown previously that benzyl isothiocyanate (BITC), which is present in edible cruciferous vegetables, inhibits breast cancer development in a transgenic mouse model. The present study was designed to determine effect of BITC on breast cancer-induced osteoclastogenesis. We employed well-established in vitro osteoclast co-culture system of Raw 264.7 murine macrophage cells with human breast cancer cells for this assessment. BITC treatment significantly inhibited the number as well as size of osteoclasts in a dose dependent manner in every co-culture experiment. In addition, BITC downregulated both mRNA and protein levels of macrophage colony stimulating factor (MCSF) and receptor activator of NF-êB ligand (RANKL) which are key factors for formation of osteoclasts. Moreover, receptor activator of NF-êB ligand (RANKL)-induced osteoclast differentiation as well as bone resorption was suppressed in the presence of BITC. On the other hand, BITC induced osteoprotegerin (OPG) acting as a decoy receptor of RANKL and negatively regulated osteoclast formation. Quantitative PCR analysis revealed that mRNA levels of osteoclastogenesis-related cytokines and proteins (IL-1â, IL-6, TNF-á, GM-CSF, OPG, RUNX2) were repressed in BITC-treated breast cancer cells. Taken together, BITC showed inhibitory activity on breast cancer-mediated osteoclastogenesis. This study was supported by the grant CA129347 awarded by the National Cancer Institute. Citation Format: Subrata K. Pore, Anuradha Sehrawat, Shivendra V. Singh. Benzyl isothiocyanate inhibits breast cancer-induced osteoclastogenesis. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 826.