tbuckley/cabot-search huggingface dataset:
Emergency endoscopic variceal ligation in cirrhotic patients with blood clots in the stomach but no active bleeding or stigmata increases the risk of rebleeding
Authors: Su Jin Kim, Cheol Woong Choi, Dae Hwan Kang, Hyung Wook Kim, Su Bum Park, Young Mi Hong, Ki Tae Yoon, Mong Cho, Hyung Seok Nam, SM Bakhtiar UI Islam
Journal: Clinical and Molecular Hepatology (2016)

This study aimed to evaluate the efficacy and safety of emergency variceal ligation for the prevention of rebleeding in cirrhotic patients who are found on initial endoscopy to have blood clots in the stomach but no actively bleeding esophageal and gastric varices or stigmata.This study included 28 cirrhotic patients who underwent emergency prophylactic EVL and 41 who underwent an elective intervention between January 2009 and June 2014. Clinical outcomes were analyzed, including the rebleeding, 6-week mortality, and rebleeding-free survival rates.The rebleeding rate was higher in the emergency than in the elective group (28.6% vs. 7.3%, P=0.041). Multivariate analysis showed that emergency prophylactic EVL (odds ratio [OR] = 7.4, 95% confidence interval [CI]=1.634.8, P=0.012) and Child-Pugh score C (OR=10.6, 95% CI=1.4-80.8, P=0.022) were associated with rebleeding. In the emergency group, the gastric varices were associated with rebleeding (OR=12.0, 95% CI=1.7-83.5, P=0.012).Emergency EVL may be associated with variceal rebleeding when blood clots are present in the stomach without active esophageal and gastric variceal bleeding or stigmata. Elective intervention should be considered as a safer strategy for preventing variceal rebleeding in this situation.
Automated Diabetic Retinopathy Image Assessment Software
Authors: Adnan Tufail, Caroline Rudisill, Catherine Egan, Venediktos V. Kapetanakis, Sebastian Salas-Vega, Christopher G. Owen, Aaron Lee, Vern Louw, John Anderson, Gerald Liew, Louis Bolter, Sowmya Srinivas, Muneeswar Nittala, SriniVas Sadda, Paul Taylor, Alicja R. Rudnicka
Journal: Ophthalmology (2016)

With the increasing prevalence of diabetes, annual screening for diabetic retinopathy (DR) by expert human grading of retinal images is challenging. Automated DR image assessment systems (ARIAS) may provide clinically effective and cost-effective detection of retinopathy. We aimed to determine whether ARIAS can be safely introduced into DR screening pathways to replace human graders.Observational measurement comparison study of human graders following a national screening program for DR versus ARIAS.Retinal images from 20 258 consecutive patients attending routine annual diabetic eye screening between June 1, 2012, and November 4, 2013.Retinal images were manually graded following a standard national protocol for DR screening and were processed by 3 ARIAS: iGradingM, Retmarker, and EyeArt. Discrepancies between manual grades and ARIAS results were sent to a reading center for arbitration.Screening performance (sensitivity, false-positive rate) and diagnostic accuracy (95% confidence intervals of screening-performance measures) were determined. Economic analysis estimated the cost per appropriate screening outcome.Sensitivity point estimates (95% confidence intervals) of the ARIAS were as follows: EyeArt 94.7% (94.2%-95.2%) for any retinopathy, 93.8% (92.9%-94.6%) for referable retinopathy (human graded as either ungradable, maculopathy, preproliferative, or proliferative), 99.6% (97.0%-99.9%) for proliferative retinopathy; Retmarker 73.0% (72.0 %-74.0%) for any retinopathy, 85.0% (83.6%-86.2%) for referable retinopathy, 97.9% (94.9%-99.1%) for proliferative retinopathy. iGradingM classified all images as either having disease or being ungradable. EyeArt and Retmarker saved costs compared with manual grading both as a replacement for initial human grading and as a filter prior to primary human grading, although the latter approach was less cost-effective.Retmarker and EyeArt systems achieved acceptable sensitivity for referable retinopathy when compared with that of human graders and had sufficient specificity to make them cost-effective alternatives to manual grading alone. ARIAS have the potential to reduce costs in developed-world health care economies and to aid delivery of DR screening in developing or remote health care settings.
An Analysis of the Costs Associated with Peripheral Blood Hematopoietic Progenitor Cell Mobilization, Collection and Cryopreservation in Patients with Lymphomas Undergoing Autologous Stem Cell Transplantation
Authors: Chitra Hosing, Veronica R. Smith, Beverly A. Rhodes, Kent H. Walters, Muzaffar H. Qazilbash, John D. McMannis, Amin M. Alousi, Marcos De Lima, Partow Kebriaei, Sergio Giralt, Issa Khouri, Richard Champlin, Uday Popat
Journal: Blood (2008)
CheckMate 067: a phase III randomized double-blind study of nivolumab (NIVO) monotherapy or NIVO combined with ipilimumab (IPI) versus IPI monotherapy in previously untreated patients (pts) with advanced melanoma (MEL)
Authors: J.D. Wolchok, V. Chiarion-Sileni, R. Gonzalez, P. Rutkowski, J. Grob, C.L. Cowey, C.D. Lao, D. Schadendorf, P.F. Ferrucci, M. Smylie, R. Dummer, A. Hill, J. Haanen, M. Maio, G. McArthur, A. Yang, L. Rollin, C. Horak, J. Larkin, F.S. Hodi
Journal: Annals of Oncology (2015)
Abstract 98: Genetic alterations of KDM4 subfamily and therapeutic effect of novel demethylase inhibitor in breast cancer
Authors: Andreana N. Holowatyj, Qin Ye, Jack Wu, Hui Liu, Lihong Zhang, Takayoshi Suzuki, Zeng-Quan Yang
Journal: Cancer Research (2015)

Abstract The histone lysine demethylase KDM4 subfamily, comprised of four members (A, B, C, and D), play critical roles in controlling transcription, chromatin architecture and cellular differentiation. Although KDM4 family members have a high degree of homology, they may play different roles in various types of breast cancer. The goal of this study is to analyze the genomic and transcriptomic alterations of the KDM4 subfamily in different subtypes of breast cancer, and explore the therapeutic potential of a novel KDM4 inhibitor in aggressive basal breast cancer. We conducted a large-scale meta-analysis of KDM4A, B, C, and D in breast cancer and identified associations among recurrent copy number alterations, gene expression and breast cancer subtypes. We examined KDM4 expression in a panel of non-tumorigenic and cancerous breast epithelial cell lines using quantitative RT-PCR and Western blot assays, and assessed global histone 3 methylation levels by Western blot in a panel of breast cancer cell lines. Next, we tested a novel inhibitor of the KDM4 demethylases, small molecule NCDM-32B, for its ability to attenuate basal breast cancer cell growth and impair metastatic potential. Finally, to examine gene expression changes induced by NCDM-32B, we conducted expression profiling and pathway analyses. We found that the KDM4 members show different expression patterns in subtypes of breast cancer. Our findings suggest that H3 global methylation levels vary among different breast cancer cell lines. We demonstrated that NCDM-32B significantly impaired viability, cellular growth and transforming phenotypes of basal breast cancer in vitro. Furthermore, NCDM-32B impaired several critical pathways and classical oncogenes, including MET, CDC26, and CDK6, that drive cellular proliferation and transformation in breast cancer. In summary, our findings add layers of information to the genomic and transcriptomic profiles of the KDM4 subfamily in different subtypes of breast cancer. We provide the first evidence that a novel KDM4 demethylase inhibitor, the small molecule NCDM-32B, led to significant inhibition of cellular growth of basal breast cancer in vitro. These findings lay the foundation for evaluating KDM4 inhibitors as therapeutic approaches against aggressive breast cancer. Citation Format: Andreana N. Holowatyj, Qin Ye, Jack Wu, Hui Liu, Lihong Zhang, Takayoshi Suzuki, Zeng-Quan Yang. Genetic alterations of KDM4 subfamily and therapeutic effect of novel demethylase inhibitor in breast cancer. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 98. doi:10.1158/1538-7445.AM2015-98
243. The Use of Thymidine Kinase Mutants as a Safeguard Switch for IPS Cells
Authors: Masashi Urabe, Ryosuke Uchibori, Akihiro Kume, Hiroaki Mizukami, Keiya Ozawa
Journal: Molecular Therapy (2016)

Induced pluripotent stem (iPS) cells have great potential for a number of applications in gene therapy and regenerative medicine. However, transplanted iPS cells spontaneously form teratoma in vivo. Residual undifferentiated iPS cells in terminally differentiated population hampers accelerated translation to human applications. In addition, forced reprogramming of somatic cells to generate iPS cells and their ability to proliferate indefinitely also raises the concern about their tumorigenicity. Introducing a suicide gene to iPS cells in advance is one of strategies to prevent tumor development. Thymidine kinase of herpes simplex virus (HSV-TK) has been applied to humans in many studies, particularly for cancer treatment. The HSV-TK phosphorylates the prodrug ganciclovir (GCV), an analog of guanosine nucleoside. The phosphorylated GCV is incorporated into host DNA and terminates the elongation of DNA strands, resulting in cell death. The therapeutic range of GCV is narrow and the administration of GCV often induces adverse reactions. Aiming at a more potent and thus less toxic TK, mutations in the HSV-TK had been screened in previous studies. However, no studies have been conducted on the direct comparison of the efficacy of mutant TKs for iPS cells. In the current study, we examined some TK mutants with substitution at the nucleoside binding site that had been reported before (Black, et al., 1996; Black, et al., 2001; Mercer, et al., 2002; Balzarini, et al., 2006). We made iPS cell clones that constitutively express individual mutant TK. Treatment of the TK-iPS clones with GCV revealed that cells with mutant SR11 (IF160 LL+A168Y), SR39 (LIF159IFL+AL168FM), Q7530 (IF160LL+AL168YF), and A168H were 10-fold more sensitive to GCV than wild type TK. Some other mutants that had been shown to have an enhanced killing activity in their original reports did not show an advantage over the wild type. These results suggested that TK mutants were more potent than the wild type and have to be screened and selected for a specific purpose.
Magnetic resonance perfusion image features uncover an angiogenic subgroup of glioblastoma patients with poor survival and better response to antiangiogenic treatment
Authors: Tiffany T. Liu, Achal S. Achrol, Lex A. Mitchell, Scott A. Rodriguez, Abdullah Feroze, Christine Kim, Navjot Chaudhary, Olivier Gevaert, Josh M. Stuart, Griffith R. Harsh, Steven D. Chang, Daniel L. Rubin
Journal: Neuro-Oncology (2016)

In previous clinical trials, antiangiogenic therapies such as bevacizumab did not show efficacy in patients with newly diagnosed glioblastoma (GBM). This may be a result of the heterogeneity of GBM, which has a variety of imaging-based phenotypes and gene expression patterns. In this study, we sought to identify a phenotypic subtype of GBM patients who have distinct tumor-image features and molecular activities and who may benefit from antiangiogenic therapies.Quantitative image features characterizing subregions of tumors and the whole tumor were extracted from preoperative and pretherapy perfusion magnetic resonance (MR) images of 117 GBM patients in 2 independent cohorts. Unsupervised consensus clustering was performed to identify robust clusters of GBM in each cohort. Cox survival and gene set enrichment analyses were conducted to characterize the clinical significance and molecular pathway activities of the clusters. The differential treatment efficacy of antiangiogenic therapy between the clusters was evaluated.A subgroup of patients with elevated perfusion features was identified and was significantly associated with poor patient survival after accounting for other clinical covariates (P values <.01; hazard ratios > 3) consistently found in both cohorts. Angiogenesis and hypoxia pathways were enriched in this subgroup of patients, suggesting the potential efficacy of antiangiogenic therapy. Patients of the angiogenic subgroups pooled from both cohorts, who had chemotherapy information available, had significantly longer survival when treated with antiangiogenic therapy (log-rank P=.022).Our findings suggest that an angiogenic subtype of GBM patients may benefit from antiangiogenic therapy with improved overall survival.
Abstract 1720: HO-3867, a selective inhibitor of stat3, suppress ovarian tumor growth and metastasis in human tissue culture and in an orthotopic mouse model
Authors: Shan Naidu, Uksha Saini, Adam C. ElNaggar, Hemant K. Bid, Ross Wanner, Kristin Bixel, Adrian A. Suarez, Chelsea Bolyard, Balveen Kaur, Paul J. Goodfellow, Periannan Kuppusamy, David Cohn, Karuppaiyah Selvendiran
Journal: Cancer Research (2015)

Abstract The lack of an efficient pre-clinical model predicting a drug's clinical response before it enters into clinical trials is a major reason behind the limited success or complete failure of most of the traditional anti-cancer compounds. In this study, we evaluate our novel, safe and selective STAT3 inhibitor HO-3867 for its anti-cancer efficacy/bio-availability using a pre-clinical relevant, orthotopic ovarian tumor model and ex-vivo human tumor tissue culture. Treatment with HO-3867 (100PPM) significantly suppressed ovarian tumor growth and metastasis when compared to the standard Cisplatin (4mg/kg). A substantial amount of HO-3867 was detected in the ovarian tumor tissues and quantified using EPR spectroscopy. Markers specific to cell proliferation (Ki-67, Cyclin D1), angiogenesis (VEGF and Kinase array) and apoptosis (caspase-3 activity) were significantly altered by treatment with HO-3867. In vivo histopathological evaluation of internal organs collected from treated tumor mice revealed no evidence of toxicity specific to HO-3867. Normal and malignant tissues were collected and TUNEL/8-OHdG staining revealed selective induction of apoptosis limited to neoplastic cells and concomitant increase in reactive oxygen species within the orthotopic tumor. Suppression of STAT3 and its downstream target proteins (cell proliferative, anti-apoptotic and angiogenic) was confirmed with proteomic array. HO-3867 treated samples had significantly reduced vessel formation (∼4 times) as compared to the untreated control as is evident by in vivo Matrigel assay. HO-3867 was also found to have cytotoxic effects in ex vivo culture of freshly collected human tumor samples, including patients with chemotherapy resistant form of the disease. Overall, these results highlight the clinical anti-cancer potential of HO-3867 using a relevant preclinical orthotopic ovarian tumor model, and provide a rationale for the inclusion of ex vivo patient tumor slice culture in oncologic drug development processes. Citation Format: Shan Naidu, Uksha Saini, Adam C. ElNaggar, Hemant K. Bid, Ross Wanner, Kristin Bixel, Adrian A. Suarez, Chelsea Bolyard, Balveen Kaur, Paul J. Goodfellow, Periannan Kuppusamy, David Cohn, Karuppaiyah Selvendiran. HO-3867, a selective inhibitor of stat3, suppress ovarian tumor growth and metastasis in human tissue culture and in an orthotopic mouse model. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 1720. doi:10.1158/1538-7445.AM2015-1720
C-10. Inducible Caspase-9 Suicide Gene Controls Adverse Effects from Alloreplete T Cells after Haploidentical Stem Cell Transplantation
Authors: Xiaoou Zhou, Gianpietro Dotti, Robert A. Krance, Caridad Martinez, Rammurti T. Kamble, Swati Naik, April G. Durett, Olga Dakhova, Barbara Savoldo, Antonio Di Stasi, David M. Spencer, Yu-Feng Lin, Hao Liu, Bambi J. Grilley, Adrian P. Gee, Cliona M. Rooney, Helen E. Heslop, Malcolm K. Brenner
Journal: Molecular Therapy (2015)

Haploidentical hematopoietic stem cell transplantation (haplo-HSCT) is an effective therapeutic strategy for transplant candidates lacking an MHC-matched donor. Removal of T cells from the graft is required, however, to prevent lethal graft-versus-host disease (GvHD). Removal of all T cells increases the risk of graft rejection, relapse, and viral and other opportunistic infections. Several strategies have been used to overcome these barriers, but it is difficult to develop a single T-cell manipulation that both eliminates alloreactivity and spares T cells representing all the available anti-viral and anti-tumor specificities in the donor's peripheral blood. We determined whether alloreplete haploidentical T cells expressing the human caspase-9 (iC9) safety gene can produce immune reconstitution in patients undergoing haplo-HSCT, and whether any resultant GvHD from these alloreplete cells can be controlled by administration of a dimerizing drug (AP1903). After transplant, patients were infused with iC9-T cells using a dose-escalation schedule from 1×104 cells/kg to 5×106 cells/kg. We measured the subsequent immune reconstitution of iC9-T cell recipients. Subjects received dimerizing drug (AP1903) if they developed GvHD. Here we reported ten patients (median age, 13 years; range, 3 – 50 years) who received increasing numbers of alloreplete donor-T cells expressing iC9 (iC9-T). All patients receiving >104 alloreplete iC9 T-lymphocytes/kg engrafted with these cells. There was rapid reconstitution of immune responses toward EBV, CMV, HHV6, VZV and BK viruses, and concomitant control of any active infections. Four patients received a single dose of AP1903, and 85-95% of circulating Cd3+CD19+ T cells were eliminated within 30 minutes of dimerizer infusion, with no recurrence of GvHD within 90 days. In one of these patients with an associated cytokine release syndrome (CRS- hyperpyrexia, high levels of pro-inflammatory cytokines and rash), symptoms and signs of this disorder resolved within 2 hours of dimerizer infusion. One patient with VZV meningitis and acute GvHD had iC9-T cells present in the CSF which were reduced by >90% after dimerizing drug. Notably, virus-specific T cells recovered even after administration of AP1903 and continued to protect the patients against infection. Hence alloreplete iC9-T cells can reconstitute immunity post-transplant and can be eliminated both from peripheral blood and CNS by administration of dimerizing drug, leading to a rapid resolution of GvHD and CRS. The approach may therefore be useful for the rapid and effective treatment of toxicities associated with infusion of engineered T lymphocytes.
Proteomic Profiling of Multiple Myeloma Using iTRAQ Labeling Followed by Multidimensional Liquid Chromatography and Tandem Mass Spectrometry.
Authors: Dominik Dytfeld, Malathi Hari, John Strahler, Dattatreya Mellacheruvu, Suchitra Subramani, Alexey Nesvizhskii, Arun Sreekumar, Andrzej J Jakubowiak
Journal: Blood (2009)
Abstract 5362: Andrographolide inhibits prostate cancer by modulating chemokine and cytokines
Authors: Hina Mir, Neeraj Kapur, Rajesh Singh, Guru Sonpavde, James W. Lillard, Shailesh Singh
Journal: Cancer Research (2015)

Abstract Treatment options for androgen independent prostate cancer (PCa) are limited. Hence, new treatment strategies are needed to treat/prevent hormone refractory advance disease. Major focus of this study was to develop non-toxic therapeutic/preventive option for PCa. Andrographolide (AG), a bioactive diterpenoid isolated from Andrographis paniculata showed dose and time dependent inhibition of PCa cells (PC3, DU145 and LNCaP). This inhibition in growth was due to selective modulation of chemokines and cytokines required for PCa cell growth and proliferation. Specifically, CXCR3 and CXCR7 expression was reduced after AG treatment. Interestingly, AG inhibited IL-6 expression, which is known to be associated with advance PCa and also highly produced by the aggressive PCa cell compared to less aggressive or normal prostatic epithelial cells. Hence, AG may be offered as a new therapeutic/preventive agent against PCa due to its ability to inhibit key chemokines and cytokines required for PCa progression and supporting hormone refractory PCa. Citation Format: Hina Mir, Neeraj Kapur, Rajesh Singh, Guru Sonpavde, James W. Lillard, Shailesh Singh. Andrographolide inhibits prostate cancer by modulating chemokine and cytokines. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 5362. doi:10.1158/1538-7445.AM2015-5362
Physical activity promotion in physiotherapy practice: a systematic scoping review of a decade of literature
Authors: Anna Lowe, Melanie Gee, Sionnadh McLean, Chris Littlewood, Carolyn Lindsay, Simon Everett
Journal: British Journal of Sports Medicine (2016)

The health benefits of physical activity (PA) have been extensively documented. Globally PA levels are low with only a small proportion of the population reaching recommended levels. Insufficient PA is seen as a major public health problem with high cost to society. Physiotherapists work with people to manage long-term conditions and are well placed to deliver individual interventions to increase PA. Despite this, little is known about the evidence that exists in this field.This scoping review comprises a comprehensive search of key databases using predetermined search terms. This is supplemented with a parallel search that incorporated novel social media strands. In line with current guidance, a robust screening process took place using agreed inclusion and exclusion criteria.31 studies met the inclusion criteria. The number of studies published annually increased over the decade. Ireland and USA yielded the largest number of publications with only 1 study from the UK. The target populations included physiotherapists and service users from a range of clinical populations. The studies were mainly quantitative and observational in design with a predominance of studies that scoped attitudes, perceptions, barriers and current practice.This reconnaissance has shown the state of the evidence to be sparse and disparate. However, the sharp rise in published work in recent years is encouraging. The predominance of scoping studies and the clear social, economic and political drivers for change in this area highlights a need for more pragmatic, interventional studies that can inform clinical practice.
Targeting STAT5 Expression Resulted in Molecular Response Improvement in Patients with Chronic Phase CML Treated with Imatinib
Authors: Philippe Rousselot, Lydia Roy, Gabriel Etienne, Laurence Legros, Aude Charbonnier, Valérie Coiteux, Pascale Cony-Makhoul, Francois-Xavier Mahon, Joelle Guilhot, Jean-Michel Cayuela, Francis Relouzat, Philippe Leboulche, Stephane Prost
Journal: Blood (2012)