tbuckley/cabot-search huggingface dataset:
Abstract 18: Spatiotemporal and Demographic Trends in Cardiovascular Disease in the US Elderly Based on 108 Million Hospitalization Records
Authors: Gitanjali M Singh, Melissa Cruz, José L Peñalvo, Jianyi Zhang, Dariush Mozaffarian, Elena N Naumova
Journal: Circulation (2017)

Background: The US population is rapidly aging, with concurrent increases in chronic disease burdens, particularly CVD. Yet, to-date, the spatial, temporal, and demographic distributions and trends in CVD incidence in the US elderly have not been characterized in detail using data with full coverage of this population. Objective: To characterize trends, 1991-2004, in CVD hospitalizations among US elderly, by single year of age/ sex/race/county/state using records from US Centers for Medicare and Medicaid (CMS), which provide full coverage of the US population aged 65+. Methods: We abstracted 108,357,431 hospitalization records compiled by CMS indicating CVD in any of 10 diagnosis codes, and tabulated total cases of CVD by sex, single year of age, state and calendar year (1991-2004). CVD incidence rates were calculated using stratum-specific population data from the US Census in conjunction with CMS records. We characterized distributions of CVD cases by single year of age for the US and further by state and calendar year, determining the sex-specific age at which the largest number of incident CVD cases were registered (peak age). Results: CVD hospitalization rates increased from 1991-2004 for women aged 65-90 and men aged 65-80, but declined in the oldest-old. In 1991, CVD hospitalization rates for women aged 75 were 48 per 100,000 population, rising to 70 per 100,000 in 2004; men aged 75 had rates of 66 per 100,000 in 1991 versus 87 per 100,000 in 2004. Nationally, peak age of CVD hospitalizations increased 1991-2004, from 77 to 83 years of age for women and from 70 to 77 years of age for men. Men and women in Southern states had among the lowest peak ages of CVD in the nation in 1991 as well as 2004. ( Figure ) Trends by race/CVD subtype are forthcoming. Conclusions: Emerging national trends and regional heterogeneity in CVD hospitalization rates and peak age of CVD hospitalization in the US elderly emphasize the need for targeted population-level policy/interventions to reduce CVD burdens and promote healthy aging.
Predictor of effectiveness of treatment intensification on overall survival in head and neck cancer (HNC)
Authors: K. Zakeri, F. Rotolo, B. Lacas, L.K. Vitzthum, Q.-T.X. Le, V. Gregoire, J. Overgaard, J. Tobias, B. Zackrisson, M.K. Parmar, B.A. Burtness, M.G. Ghi, G. Sanguineti, B. O'Sullivan, C. Fortpied, J. Bourhis, H. Shen, J. Harris, J.-P. Pignon, L.K. Mell
Journal: Annals of Oncology (2018)
The clinical relevance of visualising the peripheral retina
Authors: Nicola Quinn, Lajos Csincsik, Erin Flynn, Christine A. Curcio, Szilard Kiss, SriniVas R. Sadda, Ruth Hogg, Tunde Peto, Imre Lengyel
Journal: Progress in Retinal and Eye Research (2018)

Recent developments in imaging technologies now allow the documentation, qualitative and quantitative evaluation of peripheral retinal lesions. As wide field retinal imaging, capturing both the central and peripheral retina up to 200° eccentricity, is becoming readily available the question is: what is it that we gain by imaging the periphery? Based on accumulating evidence it is clear that findings in the periphery do not always associate to those observed in the posterior pole. However, the newly acquired information may provide useful clues to previously unrecognised disease features and may facilitate more accurate disease prognostication. In this review, we explore the anatomy and physiology of the peripheral retina, focusing on how it differs from the posterior pole, recount the history of peripheral retinal imaging, describe various peripheral retinal lesions and evaluate the overall relevance of peripheral retinal findings to different diseases.
Abstract 9812: Cardioprotection by Postconditioning With Lactate-enriched Blood in Patients With ST-elevation Myocardial Infarction
Authors: Takashi Koyama, Masahito Munakata, Takashi Akima, Masaru Shibata, Kazunori Moritani, Toshimi Kageyama, Mika Nagaoka, Hideaki Kanki, Shiro Ishikawa, Hideo Mitamura
Journal: Circulation (2015)

Objective: The beneficial effects of reperfusion therapy for ST-elevation myocardial infarction (STEMI) are attenuated by reperfusion injury. We reported that postconditioning with lactate-enriched blood (PCLeB) resulted in excellent microcirculation recovery and less inflammation in STEMI patients in our small-scale studies (AHA 2012, ACC 14). Here we analyzed all STEMI patients treated by PCLeB in our hospitals up to now. Methods: We treated 66 consecutive STEMI patients (age, 65.2 ± 14.9 y; 80.3% males) using PCLeB within 12 h of MI onset (mean ischemia time, 5.0 ± 3.0 h), including 31 patients with proximal LAD occlusion. Our modified protocol aims to achieve controlled reperfusion with cellular oxygenation and minimal lactate washout. The duration of each brief reperfusion was prolonged stepwise from 10 to 60 s. Lactated Ringer’s solution (20-30 mL), containing 28 mM lactate, was injected directly into the culprit coronary artery at the end of each reperfusion, and a balloon was quickly inflated at the lesion site, trapping lactate inside the ischemic myocardium. Each brief ischemic period lasted 60 s. After 7 cycles of balloon inflation and deflation, full reperfusion was performed, and stenting was performed thereafter. Results: The mean peak CK and CK-MB values were 2932 ± 2098 and 306 ± 224 IU/L, respectively. The mean corrected TIMI frame count after PCI was 18.5 ± 10.2 frames (normal value, 21 frames). After excluding 6 patients with extra-cardiac inflammatory disorders, the mean peak CRP value within 7 days of MI onset was 3.4 ± 2.9 mg/dL in the remaining 60 patients. Thallium-201 scintigraphy before discharge consistently revealed well-preserved myocardial viability, which appeared disproportionate to peak CK values. Thallium images of the last 10 patients with proximal LAD occlusion are presented in the Figure as a bull’s eye display labeled with each corresponding peak CK value (IU/L). Conclusion: PCLeB provides good cardioprotection in STEMI patients.
Alarming global rise in caesarean births, figures show
Authors: Jacqui Wise
Journal: BMJ (2018)

Caesarean section use is growing at an “alarming” rate, accounting for 21% of births globally in 2015—up from 12% in 2000—experts have warned.

A series of three papers published in the Lancet shows that 106 out of 169 countries have caesarean section rates above the 10% to 15% of births that is thought to be optimal.123 In at least 15 countries the caesarean rate exceeds 40%, including the Dominican Republic (58.1%), Brazil (55.5%), Egypt (55.5%), and Turkey (53.1%). In the UK, caesarean section deliveries have increased from 19.7% of births in 2000 to 26.2% in 2015.

A caesarean section can be a life saving intervention when medically indicated and should be universally available, …
Evaluation of stemness and proliferation of human breast cancer stem cells (ALDH+) supplemented with heat-activated TGF-beta1 in the secretomes of stem cells from human exfoliated deciduous teeth (SHED)
Authors: S.I. Wanandi, G. Wideani, M. Zainuri, R.R. Putri, E.W. Bachtiar, S.W.A. Jusman
Journal: Annals of Oncology (2018)
Effects of alteplase beyond 3 h after stroke in the Echoplanar Imaging Thrombolytic Evaluation Trial (EPITHET): a placebo-controlled randomised trial
Authors: Stephen M Davis, Geoffrey A Donnan, Mark W Parsons, Christopher R Levi, Kenneth S Butcher, Andre Peeters, Peter Alan Barber, Christopher Bladin, Deidre Anne De Silva, Graham Byrnes, Jonathan B Chalk, John N Fink, Thomas E Kimber, David Schultz, Peter J Hand, Judith Frayne, Graeme J Hankey, Keith Muir, Richard P Gerraty, Brian M Tress, Patricia Desmond
Journal: The Lancet (2008)
Abstract 13688: Patients With Autoimmune Disease: Not a Contraindication for Heart Transplantation
Authors: Jamie Yabuno, Jignesh Patel, Michelle Kittleson, Minh Luu, Frank Liou, Saira Siddiqui, David H Chang, Lawrence Czer, Michele Hamilton, Jon A Kobashigawa
Journal: Circulation (2015)

Introduction: Autoimmune diseases such as lupus, scleroderma, sarcoidosis, and psoriasis are associated with an increased immune response through autoantibody formation.There has been concern that this up-regulation of the immune system may increase the risk of rejection after heart transplantation. Therefore, we evaluated our patients with autoimmune diseases who subsequently underwent heart transplantation at our institution. Methods: Between 2009 and 2013 we assessed 26 patients who had a concomitant history of autoimmune disease prior to heart transplantation. Autoimmune diseases included psoriasis (5), Grave’s disease (5), sarcoidosis (5), CREST syndrome (2), Hashimoto thyroiditis (1), dermatomyositis (1), ulcerative colitis (1), systemic lupus erythematosus (1), multiple sclerosis (1), antiphospholipid syndrome (1), polymyalgia rheumatic (1), celiac disease (1), and ANCA vasculitis (1). These patients were compared to a control group of patients who did not have pre-transplant autoimmune disease (n=363). Results: Patients with pre-transplant autoimmune disease did not have any significant difference in 1- year survival, 1-year actuarial freedom from any treated rejection, 1-year actuarial freedom from treated cellular rejection, 1- year actuarial freedom from treated antibody- mediated rejection, and 1-year actuarial freedom from biopsy negative rejection (see table). Conclusions: Pre-transplant autoimmune diseases do not appear to affect post-transplant outcomes. Therefore, preexisting autoimmune disease is not a contraindication to proceed with heart transplant.
Switch to checkpoint inhibition (CPI) after targeted therapy (TT) at time of progression or during ongoing response: A retrospective analysis of patients with advanced BRAF mutated melanoma
Authors: I.L.M. Reijers, E.A. Rozeman, H. Mallo, W. Uyterlinde, S. Adriaansz, J. Lijnsvelt, S. Wilgenhof, J.V. van Thienen, J.B.A.G. Haanen, C.U. Blank
Journal: Annals of Oncology (2018)
Neoadjuvant radio-chemotherapy for esophageal cancer: A multicenter European study comparing paclitaxel/carboplatin, 5FU/cisplatin and FOLFOX
Authors: P. Allemann, S. Mantziari, M. Winiker, A.D. Wagner, A. Digklia, M. van Berge Henegouwen, S.S. Gisbertz, A. Slaman, R. van Hillegersberg, J.P. Ruurda, H. Brenkman, M. Nilsson, K. Satoshi, G. Piessen, D. Collet, C. Gronnier, N. Carrere, A. Marinho, N. Demartines, M. Schafer
Journal: Annals of Oncology (2018)
Initial results from a phase I/IIa trial evaluating BMS-986158, an inhibitor of the bromodomain and extra-terminal (BET) proteins, in patients (pts) with advanced cancer
Authors: J. Hilton, M.C. Cristea, M. Voskoboynik, S. Postel-Vinay, W. Edenfield, A. Gavai, S. Wee, N. Srivastava, A. Klippel, D. Jackson, A. Apfel, S.D. Chasalow, D. Williams, M. Donovan, B. Fischer, S. Khaldoyanidi, J.R. Diamond
Journal: Annals of Oncology (2018)
Leveraging Bioorthogonal Click Chemistry to Improve 225Ac-Radioimmunotherapy of Pancreatic Ductal Adenocarcinoma
Authors: Sophie Poty, Lukas M. Carter, Komal Mandleywala, Rosemery Membreno, Dalya Abdel-Atti, Ashwin Ragupathi, Wolfgang W. Scholz, Brian M. Zeglis, Jason S. Lewis
Journal: Clinical Cancer Research (2018)

Abstract Purpose: Interest in targeted alpha-therapy has surged due to α-particles' high cytotoxicity. However, the widespread clinical use of this approach could be limited by on-/off-target toxicities. Here, we investigated the inverse electron-demand Diels–Alder ligation between an 225Ac-labeled tetrazine radioligand and a trans-cyclooctene–bearing anti-CA19.9 antibody (5B1) for pretargeted α-radioimmunotherapy (PRIT) of pancreatic ductal adenocarcinoma (PDAC). This alternative strategy is expected to reduce nonspecific toxicities as compared with conventional radioimmunotherapy (RIT). Experimental Design: A side-by-side comparison of 225Ac-PRIT and conventional RIT using a directly 225Ac-radiolabeled immunoconjugate evaluates the therapeutic efficacy and toxicity of both methodologies in PDAC murine models. Results: A comparative biodistribution study of the PRIT versus RIT methodology underscored the improved pharmacokinetic properties (e.g., prolonged tumor uptake and increased tumor-to-tissue ratios) of the PRIT approach. Cerenkov imaging coupled to PRIT confirmed the in vivo biodistribution of 225Ac-radioimmunoconjugate but—importantly—further allowed for the ex vivo monitoring of 225Ac's radioactive daughters' redistribution. Human dosimetry was extrapolated from the mouse biodistribution and confirms the clinical translatability of 225Ac-PRIT. Furthermore, longitudinal therapy studies performed in subcutaneous and orthotopic PDAC models confirm the therapeutic efficacy of 225Ac-PRIT with the observation of prolonged median survival compared with control cohorts. Finally, a comparison with conventional RIT highlighted the potential of 225Ac-PRIT to reduce hematotoxicity while maintaining therapeutic effectiveness. Conclusions: The ability of 225Ac-PRIT to deliver a radiotherapeutic payload while simultaneously reducing the off-target toxicity normally associated with RIT suggests that the clinical translation of this approach will have a profound impact on PDAC therapy.
Interim results of fight-201, a phase II, open-label, multicenter study of INCB054828 in patients (pts) with metastatic or surgically unresectable urothelial carcinoma (UC) harboring fibroblast growth factor (FGF)/FGF receptor (FGFR) genetic alterations (GA)
Authors: A. Necchi, D. Pouessel, R. Leibowitz-Amit, A. Flechon, S. Gupta, P. Barthelemy, M. Maio, X. Zhu, E. Asatiani, G. Serbest, H. Zhen, Y. Loriot
Journal: Annals of Oncology (2018)
Phase I study of the AXL inhibitor DS-1205c in combination with osimertinib in subjects with metastatic or unresectable EGFR-mutant NSCLC
Authors: D. Planchard, P.A. Janne, H.A. Yu, D. Moro-Sibilot, T. Goldberg, X. Gu, J. Li, J. McGill, C. Yu, E. Slosberg
Journal: Annals of Oncology (2018)
Pan-HDAC Inhibitors Restore PRDM1 Response to IL21 in CREBBP-Mutated Follicular Lymphoma
Authors: Fabienne Desmots, Mikaël Roussel, Céline Pangault, Francisco Llamas-Gutierrez, Cédric Pastoret, Eric Guiheneuf, Jérôme Le Priol, Valérie Camara-Clayette, Gersende Caron, Catherine Henry, Marc-Antoine Belaud-Rotureau, Pascal Godmer, Thierry Lamy, Fabrice Jardin, Karin Tarte, Vincent Ribrag, Thierry Fest
Journal: Clinical Cancer Research (2018)

Abstract Purpose: Follicular lymphoma arises from a germinal center B-cell proliferation supported by a bidirectional crosstalk with tumor microenvironment, in particular with follicular helper T cells (Tfh). We explored the relation that exists between the differentiation arrest of follicular lymphoma cells and loss-of-function of CREBBP acetyltransferase. Experimental Design: The study used human primary cells obtained from either follicular lymphoma tumors characterized for somatic mutations, or inflamed tonsils for normal germinal center B cells. Transcriptome and functional analyses were done to decipher the B- and T-cell crosstalk. Responses were assessed by flow cytometry and molecular biology including ChIP-qPCR approaches. Results: Conversely to normal B cells, follicular lymphoma cells are unable to upregulate the transcription repressor, PRDM1, required for plasma cell differentiation. This defect occurs although the follicular lymphoma microenvironment is enriched in the potent inducer of PRDM1 and IL21, highly produced by Tfhs. In follicular lymphoma carrying CREBBP loss-of-function mutations, we found a lack of IL21-mediated PRDM1 response associated with an abnormal increased enrichment of the BCL6 protein repressor in PRDM1 gene. Moreover, in these follicular lymphoma cells, pan-HDAC inhibitor, vorinostat, restored their PRDM1 response to IL21 by lowering BCL6 bound to PRDM1. This finding was reinforced by our exploration of patients with follicular lymphoma treated with another pan-HDAC inhibitor. Patients showed an increase of plasma cell identity genes, mainly PRDM1 and XBP1, which underline the progression of follicular lymphoma B cells in the differentiation process. Conclusions: Our data uncover a new mechanism by which pan-HDAC inhibitors may act positively to treat patients with follicular lymphoma through the induction of the expression of plasma cell genes.
Prediction of Arteriovenous Fistula Clinical Maturation from Postoperative Ultrasound Measurements: Findings from the Hemodialysis Fistula Maturation Study
Authors: Michelle L. Robbin, Tom Greene, Michael Allon, Laura M. Dember, Peter B. Imrey, Alfred K. Cheung, Jonathan Himmelfarb, Thomas S. Huber, James S. Kaufman, Milena K. Radeva, Prabir Roy-Chaudhury, Yan-Ting Shiu, Miguel A. Vazquez, Heidi R. Umphrey, Lauren Alexander, Carl Abts, Gerald J. Beck, John W. Kusek, Harold I. Feldman
Journal: Journal of the American Society of Nephrology (2018)

Background The utility of early postoperative ultrasound measurements in predicting arteriovenous fistula (AVF) clinical maturation is uncertain. Methods We investigated the relationships of ultrasound parameters with AVF clinical maturation in newly created AVF, measured at 1 day and 2 and 6 weeks, in 602 participants of a multicenter, observational cohort study. A backward elimination algorithm identified ultrasound measurements that independently predicted unassisted and overall AVF maturation. Candidate variables included AVF blood flow, diameter, and depth, upper arm arterial diameter, presence of stenosis, presence of accessory veins, seven case-mix factors (age, sex, black race, AVF location, diabetes, dialysis status, and body mass index), and clinical center. We evaluated the accuracy of the resulting models for clinical prediction. Results At each ultrasound measurement time, AVF blood flow, diameter, and depth each predicted in a statistically significant manner both unassisted and overall clinical maturation. Moreover, neither the remaining ultrasound parameters nor case-mix factors were associated with clinical AVF maturation after accounting for blood flow, diameter, and depth, although maturation probabilities differed among clinical centers before and after accounting for these parameters. The crossvalidated area under the receiver operating characteristic curve for models constructed using these three ultrasound parameters was 0.69, 0.74, and 0.79 at 1 day and 2 and 6 weeks, respectively, for unassisted AVF clinical maturation and 0.69, 0.71, and 0.76, respectively, for overall AVF maturation. Conclusions AVF blood flow, diameter, and depth moderately predicted unassisted and overall AVF clinical maturation. The other factors considered did not further improve AVF maturation prediction.
Identification of selective inhibition of phospho-S6 ribosomal protein in XK469 sensitive leukemia cell lines using functional proteomic analysis
Authors: Raoul Tibes, Yiling Lu, Doris R. Siwak, Brian Hennessy, Ruth Lapushin, Gordon Mills
Journal: Cancer Research (2005)

3279  Introduction XK469 is a new potent anti-tumor agent sponsored by the NCI for clinical development. XK469’s proposed mechanism of action is selective Topoisomerase IIβ inhibition. However, recent studies demonstrate a dissociation between concentrations required to inhibit topoisomerase and those inhibiting cell proliferation. Alternative suggested modes of action are interference with cell cycle progression or signaling pathways, such as MAPK inhibition. Using a new high throughput functional proteomic technology, reverse phase protein array (RPPA), we identified selective inhibition of the mTor/p70S6K downstream target phosphoS6 ribosomal protein, a key translational regulatory protein, by XK469. Methods The RPPA technique was used to concurrently study six different leukemia cell lines (U937, HL60, OCI-AML3, KG-1, MO7e, TF-1) for expression change of 20 proteins and their corresponding phospho-proteins during XK469 treatment. Proliferation was assessed by MTT dye conversion and apoptosis by flow-cytometric AnnexinV staining. Results TF-1, MO7e and OCI-AML3 cell lines were dose dependently more sensitive (50-65% growth inhibition at max. concentrations of 100 μM), than U937, HL60 and KG-1 cells (20-30% inhibition). The more sensitive cell lines demonstrated higher basal levels of phospho-S6 ribosomal protein and p53 than did the less sensitive cell lines. There was selective and marked decrease in phospho-S6protein levels in the XK469 sensitive cell lines (TF-1, MO7e, OCI-AML3), as determined by RPPA, but also in the less sensitive KG-1 cells.Apoptosis was only minimally increased (TF-1, Mo7e cells) and other signaling pathways (STAT, MAPK and upstream Akt members including mTor, p70S6K, GSK, PTEN) were not affected at the doses assessed. In the less sensitive cell lines (U937, HL60) phospho-S6protein levels were reduced to a lesser extent, while apoptosis was more than doubled. There was mild decrease in phosphorylated mTor levels in these cell lines. The strength and validation of comprehensive phosphoproteomics profiling using RPPA was demonstrated, for example, in correctly identifying U937 as a PTEN mutant. Conclusion Selective inhibition of S6 ribosomal protein in XK469 sensitive leukemia cells suggests a novel mechanism of action for XK469. This action seems to be independent of apoptosis and mediated through antiproliferative signals downstream of mTor/p70S6K. Further, the activity of the AKT/mTOR pathway and its downstream effectors (including S6protein and p53), if confirmed in further studies, could potentially be used to identify patients likely to show increased response to XK469. To validate the identified biological targets and to assess molecular markers of response, we will apply the RPPA technology to samples from leukemia patients enrolled in the XK469 clinical trial at MD Anderson Cancer Center.