tbuckley/cabot-search huggingface dataset:
Abstract 37: Limited Knowledge of the Crash Call Number Among Hospital Staff - a Call for Standardization
Authors: Bo Løfgren, Camilla Blindbæk Larsen, Maja Lynge Rasmussen, Finn Lund Henriksen, Niels Henrik Krarup
Journal: Circulation (2010)

Introduction:  In-hospital cardiac arrest carries a poor prognosis. Any delay in activating the hospital resuscitation team may jeopardize survival. Hospital staff often works at multiple sites and a lack of a uniform crash call number may contribute to delayed activation of the resuscitation team. The aim of this study was to quantify crash call numbers in all public hospitals in Denmark, and furthermore to determine the knowledge of the crash call number among hospital staff.   Methods:  All public Danish hospitals were contacted by telephone to quantify the crash call numbers in use. We randomly sampled two university hospitals and five county hospitals, and questionnaires were distributed among hospital staff to investigate the knowledge of the crash call number. The questionnaire included questions on occupation, knowledge of crash call number and how that knowledge was obtained. In addition, the staff was asked to disclose employments at other hospitals within the last 12 months and their respective crash call numbers.   Results:  At 74 hospitals 41 different crash call numbers were used. The most prevalent numbers were “2222” (n=12), “4444” (n=2), “7000” (n=2) and “2011” (n=2). Based on 648 questionnaires (response rate 78%) the overall average knowledge of the crash call number was 49.5% (Physicians: 48% (n=179); nursing personal: 58% (n=201); service personal: 52% (n=168); miscellaneous: 31% (n=100)). The primary source of knowledge was introduction to the hospital (36%), boards or labels on phones (23%) and participation in an emergency situation (12%). A minor part of the staff (18%) had 1 – 3 employments at other hospitals within the previous 12 months. Recollection of the crash call numbers at these hospitals were 21%, 2% and 4% respectively.   Conclusions:  We demonstrate a pronounced diversity in the crash call numbers in use. The knowledge of the crash call number is limited among hospital staff. A standardized crash call number may strengthen knowledge and improve activation of the resuscitation team.
Marketing of unproven stem cell–based interventions: A call to action
Authors: Douglas Sipp, Timothy Caulfield, Jane Kaye, Jan Barfoot, Clare Blackburn, Sarah Chan, Michele De Luca, Alastair Kent, Christopher McCabe, Megan Munsie, Margaret Sleeboom-Faulkner, Jeremy Sugarman, Esther van Zimmeren, Amy Zarzeczny, John E. J. Rasko
Journal: Science Translational Medicine (2017)

Commercial promotion of unsupported therapeutic uses of stem cells is a global problem that should be addressed by coordinated approaches at the national and international levels.
Targeting the mesenchymal subtype in glioblastoma and other cancers via inhibition of diacylglycerol kinase alpha
Authors: Inan Olmez, Shawn Love, Aizhen Xiao, Laryssa Manigat, Peyton Randolph, Brian D McKenna, Brian P Neal, Salome Boroda, Ming Li, Breanna Brenneman, Roger Abounader, Desiree Floyd, Jeongwu Lee, Ichiro Nakano, Jakub Godlewski, Agnieszka Bronisz, Erik P Sulman, Marty Mayo, Daniel Gioeli, Michael Weber, Thurl E Harris, Benjamin Purow
Journal: Neuro-Oncology (2017)

The mesenchymal phenotype in glioblastoma (GBM) and other cancers drives aggressiveness and treatment resistance, leading to therapeutic failure and recurrence of disease. Currently, there is no successful treatment option available against the mesenchymal phenotype.We classified patient-derived GBM stem cell lines into 3 subtypes: proneural, mesenchymal, and other/classical. Each subtype's response to the inhibition of diacylglycerol kinase alpha (DGKα) was compared both in vitro and in vivo. RhoA activation, liposome binding, immunoblot, and kinase assays were utilized to elucidate the novel link between DGKα and geranylgeranyltransferase I (GGTase I).Here we show that inhibition of DGKα with a small-molecule inhibitor, ritanserin, or RNA interference preferentially targets the mesenchymal subtype of GBM. We show that the mesenchymal phenotype creates the sensitivity to DGKα inhibition; shifting GBM cells from the proneural to the mesenchymal subtype increases ritanserin activity, with similar effects in epithelial-mesenchymal transition models of lung and pancreatic carcinoma. This enhanced sensitivity of mesenchymal cancer cells to ritanserin is through inhibition of GGTase I and downstream mediators previously associated with the mesenchymal cancer phenotype, including RhoA and nuclear factor-kappaB. DGKα inhibition is synergistic with both radiation and imatinib, a drug preferentially affecting proneural GBM.Our findings demonstrate that a DGKα-GGTase I pathway can be targeted to combat the treatment-resistant mesenchymal cancer phenotype. Combining therapies with greater activity against each GBM subtype may represent a viable therapeutic option against GBM.
The role of serum tumour markers, inflammation-based markers and circulating tumour cells as surrogate biomarkers of early response to neoadjuvant systemic treatment in patients with resectable gastric cancer.
Authors: Katarzyna Marcisz-Grzanka, Tomasz Olesinski, Jakub Pałucki, Małgorzata Fuksiewicz, Maria Kowalska, Beata Kotowicz, Andrzej Tysarowski, Jacek Krynski, Anna Cencelewicz-Lesikow, Jacek Zwolinski, Ewa Kosakowska, Dorota Czyżewska, Katarzyna Seliga, Lucjan Wyrwicz
Journal: Annals of Oncology (2017)
Gene Expression Analysis and Correlation with Pathological Outcome to Neoadjuvant Chemoradiation in Oesophageal Cancer
Authors: CM Gillham, N Miller, C Muldoon, S Duggan, FM Smith, N Ravi, D Hollywood, JV Reynolds
Journal: Endoscopy (2006)

Aims: A complete pathological response (pCR) to neoadjuvant chemoradiation is associated with optimum outcomes in resectable oesophageal cancer. Predicting the approximate 20% who achieve a pCR may have great therapeutic implications, and this study aimed to identify a predictive molecular signature using gene expression microarray technology.
Prognostic and predictive role of neutrophil/lymphocytes ratio in metastatic colorectal cancer: a retrospective analysis of the TRIBE study by GONO
Authors: E. Dell’Aquila, C. Cremolini, T. Zeppola, S. Lonardi, F. Bergamo, G. Masi, M. Stellato, F. Marmorino, M. Schirripa, F. Urbano, M. Ronzoni, G. Tomasello, A. Zaniboni, P. Racca, A. Buonadonna, G. Allegrini, E. Fea, S. Di Donato, S. Chiara, G. Tonini, D. Tomcikova, L. Boni, A. Falcone, D. Santini
Journal: Annals of Oncology (2018)

Neutrophil/lymphocyte ratio (NLR), defined as absolute neutrophils count divided by absolute lymphocytes count, has been reported as poor prognostic factor in several neoplastic diseases but only a few data are available about unresectable metastatic colorectal cancer (mCRC) patients (pts). The aim of our study was to evaluate the prognostic and predictive role of NLR in the TRIBE trial.Pts enrolled in TRIBE trial were included. TRIBE is a multicentre phase III trial randomizing unresectable and previously untreated mCRC pts to receive FOLFOXIRI or FOLFIRI plus bevacizumab. A cut-off value of 3 was adopted to discriminate pts with low (NLR < 3) versus high (NLR ≥ 3) NLR, as primary analysis. As secondary analysis, NLR was treated as an ordinal variable with three levels based on terciles distribution.NLR at baseline was available for 413 patients. After multiple imputation at univariate analysis, patients with high NLR had significantly shorter progression-free survival (PFS) [hazard ratio (HR) 1.27 (95% CI 1.05-1.55), P = 0.017] and overall survival (OS) [HR 1.56 (95% CI 1.25-1.95), P < 0.001] than patients with low NLR. In the multivariable model, NLR retained a significant association with OS [HR 1.44 (95% CI 1.14-1.82), P = 0.014] but not with PFS [HR 1.18 (95% CI 0.95-1.46), P = 0.375]. No interaction effect between treatment arm and NLR was evident in terms of PFS (P for interaction = 0.536) or OS (P for interaction = 0.831). Patients with low [HR 0.84 (95% CI 0.64-1.08)] and high [HR 0.73 (95% CI 0.54-0.97)] NLR achieved similar PFS benefit from the triplet and consistent results were obtained in terms of OS [HR 0.83 (95% CI 0.62-1.12) for low NLR; HR 0.82 (95% CI 0.59-1.12) for high NLR].This study confirmed the prognostic role of NLR in mCRC pts treated with bevacizumab plus chemotherapy in the first line, showing the worse prognosis of pts with high NLR. The advantage of the triplet is independent of NLR at baseline.
Abstract 110: The Estrogen-related Receptor Gamma Promotes Maturation of iPSC-derived Cardiac Myocytes
Authors: Tomoya Sakamoto, Teresa C Leone, Huei-Sheng Vincent Chen, Rick B Vega, Daniel P Kelly
Journal: Circulation Research (2016)

The mammalian heart has a tremendous energy requirement to support normal contractile function. Recently, our group discovered that the estrogen-related receptor γ (ERRγ) coordinately controls oxidative energy metabolism and the type I fiber program in skeletal muscle. We hypothesized that this circuit is also operative in heart, serving to match capacity to produce ATP with energy utilizing processes such as contraction and ion transport. To identify downstream targets and pathways of ERRγ in cardiac myocytes, RNA-sequencing (RNA-seq) was conducted in neonatal rat ventricular myocytes (NRVMs) overexpressing ERRγ. ERRγ induced the expression of genes involved in mitochondrial oxidative phosphorylation, fatty acid oxidation, and the TCA cycle. Interestingly, ERRγ also induced expression of a broad program of adult cardiac contractile and structural genes including Myh6 (αMHC) and Ca 2+ handling genes such as Atp2a2 (SERCA2A). ERRγ-mediated activation of adult genes occurred concomitant with the suppression of fetal cardiac and embryonic/perinatal fast skeletal isoform contractile protein gene expression including Myh7 (βMHC), Myl1 and Myh3/8 . These results prompted us to explore the role of ERRγ in differentiation and maturation of human iPS-derived cardiac myocytes (iPSC-CM). The expression level of ERRγ was markedly upregulated during the transition to cardiac lineage commitment in parallel with induction of cardiogenic transcription factors (e.g. NKX2.5 and GATA4). Forced expression of ERRγ in iPSC-CM activated the broad adult cardiac myocyte program including oxidative metabolism and adult contractile gene expression. Of note, ERRγ increased MYH6 expression while decreasing expression of MYH7 and the fetal gene markers NPPA (ANF) and NPPB (BNP). The expression of TNNI3 , thought to be a marker of mature adult cardiomyocytes, was also induced by ERRγ. Conversely, CRISPR-Cas9n deletion of ERRγ in iPSC-CM resulted in diminished mitochondrial energy metabolic and adult cardiac contractile gene expression. These data provide evidence that ERRγ is a key nodal regulator of cardiac myocyte determination and terminal maturation. ERR signaling is a candidate target for driving iPSC-CM to the “adult” cardiac myocyte phenotype.
Prospective registry of multiplex testing (PROMPT): A web-based platform to assess cancer risk of genetic variants.
Authors: Michael Francis Walsh, Pragna Gaddam, Laura Digiovanni, Judith Balmaña, Jill S Dolinsky, Taylor Sittler, Rachel Klein, Stephen E Lincoln, Brian Allen, Justin Leighton, Charles Strom, Vanessa Ranger-Miller, Kyle Brown, Judy Ellen Garber, Fergus J. Couch, Susan M. Domchek, Mark E. Robson, Kenneth Offit
Journal: Journal of Clinical Oncology (2016)

1518 Background: Multiplex genetic testing results in detection of pathogenic mutations of low, intermediate and high penetrance, as well as variants of uncertain clinical significance. Methods: A web-based interface was constructed to allow individual patients and families who have had germline panel testing to consent to ongoing research under an IRB approved protocol. Phase one recruitment was facilitated by engagement of 7 commercial testing laboratories, genetic counselors, academic centers and crowd sourcing. Genetic variant, personal and family history, other phenotypic data were recorded. In phase two, individuals will be asked to consent to ascertainment of samples from family members for cosegregation studies, and collection of biospecimens for functional genomic analysis. Data collected will be deposited in public databases. Results: As of January 14th, 2016,1537 individuals from 4 continents have enrolled onto PROMPT. Of these, 34% had no personal history of cancer, 50% were diagnosed with breast cancer, 4% ovarian cancer, 3% colon cancer, 3% skin cancer, and 6% with other cancer types. Most of the cohort (94%) was female. Of 756 variants in the PROMPT database, 36.2% were pathogenic, 3.4% pathogenic or likely pathogenic, 2% likely pathogenic, 1.9 % likely benign, 1.6% benign, 14.4% alterations with conflicting interpretation, 1.9% other designations and 38.6% variants of uncertain significance. Genes most commonly reported as altered included: ATM, CHEK2, BRCA2, PALB2, BRCA1, BARD1, CDH1, BRIP1, TP53, MSH6, MSH2, APC, NBN, RAD51C, MUTYH, PMS2, RAD50, PTEN, RAD51D, MLH1, and NF1. Conclusions: The first phase of PROMPT collected and classified genotypic and phenotypic information associated with variants detected by multiplex testing. Continued ascertainment is underway. The second phase of the study will entail segregation and functional studies. Cancer care providers and laboratories are encouraged to refer their patients to PROMPT. With ENIGMA, ClinVar, ClinGen and other efforts, web based registries such as PROMPT provide a means to assess both the frequency, as well as clinical validity and clinical utility of genomic variants detected by multiplex testing.
Plasma pharmacokinetics, oral bioavailability, and interspecies scaling of the DNA methyl transferase inhibitor, zebularine (NSC 309132), in mice, rats, and Rhesus monkeys
Authors: Julianne L. Holleran, Robert A. Parise, Erin Joseph, Julie L. Eiseman, Joseph M. Covey, Elizabeth R. Glaze, Alexander V. Lyubimov, Ya-Fei Chen, David Z. D’Argenio, Merrill J. Egorin
Journal: Cancer Research (2005)

4167    Purpose : We developed and validated a liquid chromatography/mass spectrometric (LC/MS) method and performed pharmacokinetic studies in mice, rats, and monkeys to define the plasma pharmacokinetics and bioavailability of zebularine, an inhibitor of DNA methyltransferase being considered for clinical evaluation.  Experimental Design : Stability and protein binding of zebularine were characterized in mouse, rat, dog, monkey, and human plasma. Pharmacokinetic studies were performed in CD 2 F 1  mice (100 mg/kg i.v. or 1,000 mg/kg p.o.), Fischer 344 rats (50 mg/kg i.v., 250 mg/kg p.o., or 500 mg/kg p.o.), and rhesus monkeys (either 500 mg/kg or 1,000 mg/kg i.v. and p.o.). Plasma zebularine concentration versus time data were analyzed with non-compartmental and compartmental methods. Interspecies scaling was performed according to standard methods.  Results : In mice, plasma zebularine concentrations declined with terminal half-lives (t 1/2 ) of 40 min and 91 min after 100 mg/kg i.v. and 1,000 mg/kg p.o., respectively. Zebularine plasma concentration versus time curves (AUC) after 100 mg/kg i.v. and 1,000 mg/kg p.o.doses were 7,323 μg/ml · min and 4,935 μg/ml · min, respectively, corresponding to a total body clearance (Cl tb ) of 13.65 ml/min/kg, an apparent total body clearance (Cl app ) of 203 ml/min/kg, and an oral bioavailability of 6.7%. In rats, plasma zebularine concentration declined with t 1/2  of 363 min, 110 min, and 126 min after 50 mg/kg i.v., 250 mg/kg p.o., and 500 mg/kg p.o. doses, respectively. The zebularine AUC’s after 50 mg/kg i.v., 250 mg/kg p.o., and 500 mg/kg p.o. doses were 12,526 μg/ml · min, 1,969 μg/ml · min, and 7,612 μg/ml · min, corresponding to a Cl tb  3.99 ml/min/kg for the 50 mg/kg i.v. dose and Cl app  of 127 and 66 ml/min/kg for the 250 mg/kg and 500 mg/kg p.o. doses, respectively. Oral bioavailabilities of 3.1% and 6.1% were calculated for the 250 mg/kg and 500 mg/kg p.o. doses, respectively. In rhesus monkeys, the zebularine t 1/2  ranged from 70 to 150 min, Cl tb  ranged from 3.55 to 10.85 ml/min/kg after i.v. administration and Cl app  ranged from 886 to 39,572 ml/min/kg after oral administration of 500 and 1,000 mg/kg. Zebularine oral bioavailability was less than 1% in each of the four monkeys studied. Species scaling produced a relationship described by the equation: CL tb  = 6.46 (weight 0.9 )  Conclusions : Zebularine has limited oral bioavailability, which is lower in non-human primates than in rodents. Interspecies scaling projects a zebularine CL tb  of 296 ml/min in a 70-kg human, but clinical studies will be required to characterize the actual CL tb  and oral bioavailability in humans. The LC/MS assay developed should be applicable in those studies.
Elimination of mother-to-child transmission of HIV and Syphilis (EMTCT): Process, progress, and program integration
Authors: Melanie Taylor, Lori Newman, Naoko Ishikawa, Maura Laverty, Chika Hayashi, Massimo Ghidinelli, Razia Pendse, Lali Khotenashvili, Shaffiq Essajee
Journal: PLoS Medicine (2017)

Melanie Taylor and colleagues discuss progress towards eliminating vertical transmission of HIV and syphilis.
Acquired Immune Resistance Follows Complete Tumor Regression without Loss of Target Antigens or IFNγ Signaling
Authors: Marco Donia, Katja Harbst, Marit van Buuren, Pia Kvistborg, Mattias F. Lindberg, Rikke Andersen, Manja Idorn, Shamaila Munir Ahmad, Eva Ellebæk, Anja Mueller, Paolo Fagone, Ferdinando Nicoletti, Massimo Libra, Martin Lauss, Sine Reker Hadrup, Henrik Schmidt, Mads Hald Andersen, Per thor Straten, Jonas A. Nilsson, Ton N. Schumacher, Barbara Seliger, Göran Jönsson, Inge Marie Svane
Journal: Cancer Research (2017)

Abstract Cancer immunotherapy can result in durable tumor regressions in some patients. However, patients who initially respond often experience tumor progression. Here, we report mechanistic evidence of tumoral immune escape in an exemplary clinical case: a patient with metastatic melanoma who developed disease recurrence following an initial, unequivocal radiologic complete regression after T-cell–based immunotherapy. Functional cytotoxic T-cell responses, including responses to one mutant neoantigen, were amplified effectively with therapy and generated durable immunologic memory. However, these immune responses, including apparently effective surveillance of the tumor mutanome, did not prevent recurrence. Alterations of the MHC class I antigen-processing and presentation machinery (APM) in resistant cancer cells, but not antigen loss or impaired IFNγ signaling, led to impaired recognition by tumor-specific CD8+ T cells. Our results suggest that future immunotherapy combinations should take into account targeting cancer cells with intact and impaired MHC class I–related APM. Loss of target antigens or impaired IFNγ signaling does not appear to be mandatory for tumor relapse after a complete radiologic regression. Personalized studies to uncover mechanisms leading to disease recurrence within each individual patient are warranted. Cancer Res; 77(17); 4562–6. ©2017 AACR.
Punctate Radiation Dermatitis of the Foot and Ankle Caused by Distal Embolization of 90Y Microspheres During Liver Directed Therapy
Authors: Benjamin B. Nia, Emily S. Nia, Ryan J. Avery, Phillip H. Kuo, Charles T. Hennemeyer
Journal: Clinical Nuclear Medicine (2017)

A 41-year-old man with gastric adenocarcinoma presented with hepatic metastases. The metastases were refractory to systemic chemotherapy, so radioembolization with Y microspheres was performed. Because of stasis or saturation of the tumor with embolic particles, 79% of the microspheres were injected. At follow-up, the patient complained of "red bumps" that had developed on his right foot/ankle the day after the radioembolization. Because a portion of the dose was still in the catheter when withdrawn from the right femoral artery, the interventional radiologist used a Geiger counter to confirm radioactivity in the cutaneous lesions and thus the distal embolization of the microspheres.
Trial of Electrical Direct-Current Therapy versus Escitalopram for Depression
Authors: Andre R Brunoni, Adriano H Moffa, Bernardo Sampaio-Junior, Lucas Borrione, Marina L Moreno, Raquel A Fernandes, Beatriz P Veronezi, Barbara S Nogueira, Luana V M Aparicio, Lais B Razza, Renan Chamorro, Luara C Tort, Renerio Fraguas, Paulo A Lotufo, Wagner F Gattaz, Felipe Fregni, Isabela M Benseñor
Journal: New England Journal of Medicine (2017)

We compared transcranial direct-current stimulation (tDCS) with a selective serotonin-reuptake inhibitor for the treatment of depression.In a single-center, double-blind, noninferiority trial involving adults with unipolar depression, we randomly assigned patients to receive tDCS plus oral placebo, sham tDCS plus escitalopram, or sham tDCS plus oral placebo. The tDCS was administered in 30-minute, 2-mA prefrontal stimulation sessions for 15 consecutive weekdays, followed by 7 weekly treatments. Escitalopram was given at a dose of 10 mg per day for 3 weeks and 20 mg per day thereafter. The primary outcome measure was the change in the 17-item Hamilton Depression Rating Scale (HDRS-17) score (range, 0 to 52, with higher scores indicating more depression). Noninferiority of tDCS versus escitalopram was defined by a lower boundary of the confidence interval for the difference in the decreased score that was at least 50% of the difference in the scores with placebo versus escitalopram.A total of 245 patients underwent randomization, with 91 being assigned to escitalopram, 94 to tDCS, and 60 to placebo. In the intention-to-treat analysis, the mean (±SD) decrease in the score from baseline was 11.3±6.5 points in the escitalopram group, 9.0±7.1 points in the tDCS group, and 5.8±7.9 points in the placebo group. The lower boundary of the confidence interval for the difference in the decrease for tDCS versus escitalopram (difference, -2.3 points; 95% confidence interval [CI], -4.3 to -0.4; P=0.69) was lower than the noninferiority margin of -2.75 (50% of placebo minus escitalopram), so noninferiority could not be claimed. Escitalopram and tDCS were both superior to placebo (difference vs. placebo, 5.5 points [95% CI, 3.1 to 7.8; P<0.001] and 3.2 points [95% CI, 0.7 to 5.5; P=0.01], respectively). Patients receiving tDCS had higher rates of skin redness, tinnitus, and nervousness than did those in the other two groups, and new-onset mania developed in 2 patients in the tDCS group. Patients receiving escitalopram had more frequent sleepiness and obstipation than did those in the other two groups.In a single-center trial, tDCS for the treatment of depression did not show noninferiority to escitalopram over a 10-week period and was associated with more adverse events. (Funded by Fundação de Amparo à Pesquisa do Estado de São Paulo and others; ELECT-TDCS ClinicalTrials.gov number, NCT01894815 .).
Discrepancy between the clinical and histopathologic diagnosis of soft tissue vascular malformations
Authors: Sophie E.R. Horbach, Amalia M. Utami, Lorine B. Meijer-Jorna, J.H. Sillevis Smitt, Phyllis I. Spuls, Chantal M.A.M. van der Horst, Allard C. van der Wal
Journal: Journal of the American Academy of Dermatology (2017)
Bifidobacterium infantis Modulates Pathogen-Induced CCL20 Secretion by Human Intestinal Epithelial Cells
Authors: AM O'Hara, J Ryan, B Sheil, A Fanning, L O'Mahony, F Shanahan
Journal: Endoscopy (2006)

Aims: The chemokine CCL20 is secreted by human intestinal epithelial cells (IEC) in response to infection by various enteropathogenic bacteria or stimulation with bacterial flagellin. Here we investigated IEC responses to individual pathogenic and commensal bacteria as well as the modulatory effects of commensal bacteria on pathogen-induced CCL20 secretion.
Direct Conversion of Adult Endothelial Cells into Immunecompetent Long-Term Engraftable Clinically Scalable Hematopoietic Stem Cells: Pathway to Therapeutic Translation
Authors: Raphael Lis, Charles Harrasch, Michael Gustave Poulos, Jose Gabriel Duran, William Schachterle, Michael Ginsberg, Arash Rafii, Koji Shido, Nancy A. Speck, Jason M. Butler, Joseph M. Scandura, Shahin Rafii
Journal: Blood (2016)