tbuckley/cabot-search huggingface dataset:
PTH-017 Large proportions of patients with renal failure have significant upper gastrointestinal findings at endoscopy. Results from a tertiary referral centre
Authors: S K Butt, S Greenfield, M Carter, D Rowlands, I Sargeant
Journal: Gut (2010)

<h3>Introduction</h3> The demand for endoscopy is ever increasing as is the rise in overall costs of endoscopy and waiting times. Adherence to appropriate indications is essential to prevent the rise in proportions of negative and hence unnecessary endoscopies. Patients with chronic renal impairment are one group of patients who may have significant gastrointestinal symptoms and often form an important number of referrals to the endoscopy unit for upper GI endoscopy. These patients are of variable complexity and often have multi-organ disease. Anaemia can often be the indication for referral despite this being part of the disease complex. We wanted to investigate the indications and endoscopic findings in renal patients from a busy tertiary referral centre. <h3>Methods</h3> The aim was to assess the findings at gastroscopy in patients with renal failure from a renal tertiary referral centre. This was a single centre, retrospective analysis of renal patients who were referred for gastroscopy. Patient details were obtained from the CIPTS database by isolating patients under the named renal physician referrer. Gastroscopy reports between 2006 until April 2009 were obtained and analysed for indications and diagnosis at endoscopy. <h3>Results</h3> A total of 90 gastroscopies in 73 patients were conducted during the study period. The age range was 45–92 and 58% were male patients. 86% of the gastroscopies were inpatient procedures. The majority of indications for gastroscopies included anaemia, haematemesis or melaena and these accounted for the indication 75 times either alone or in combination. Out of 90 gastroscopies 31 (34%) were considered as normal. Those gastroscopies in the normal category included reports of normal gastroscopies, hiatus hernias or minimal gastritis. All else was classed as abnormal (66%). Erosive lesions within the upper GI tract were diagnosed 47 times in the 90 reports (52%). These included oesophageal, gastric and duodenal ulcers, mallory weiss tears, duodenal erosions, and pyloric and duodenal stenoses. Three reports had cancer (1 duodenal, 2 oesophageal), and vascular lesions (angiodysplasia, telangiectasia, portal gastropathy, varices) were reported 14 (16%) times. <h3>Conclusion</h3> Two-thirds of patients with renal failure referred for an upper GI endoscopy have abnormal findings. The majority have erosive disorders as opposed to vascular lesions as previously reported to be associated in the literature. Our study demonstrates a high pick-up rate of in-patients with renal failure and we recommend that the threshold to endoscopy in such patients should be low, and anaemia should not be ascribed to one of chronic disease without performing a gastroscopy.
Basal Ganglia Dysfunction Contributes to Physical Inactivity in Obesity
Authors: Danielle M. Friend, Kavya Devarakonda, Timothy J. O’Neal, Miguel Skirzewski, Ioannis Papazoglou, Alanna R. Kaplan, Jeih-San Liow, Juen Guo, Sushil G. Rane, Marcelo Rubinstein, Veronica A. Alvarez, Kevin D. Hall, Alexxai V. Kravitz
Journal: Cell Metabolism (2016)
TRAF6-Dominant Negative Peptides Show Potent Inhibitory Effects On Multiple Myeloma, Osteoclast Formation and Bone Resorption.
Authors: Mingjie Li, Eric Sanchez, Jennifer Li, Cathy S Wang, Jing Shen, Mengyin Hu, Crystal Leung, Jessica Wang, Emily Wong, Anoushka Adler, Zhi-Wei Li, Haiming Chen, Benjamin Bonavida, James R. Berenson
Journal: Blood (2009)
OC-004 Effect of hookworm treatment on active Crohn's disease
Authors: P Fortun, V Shepherd, V Moroz, D Pritchard, C J Hawkey
Journal: Gut (2010)

<h3>Introduction</h3> Parasites are under consideration as therapy for Crohn9s disease and hookworm treatment is marketed for this purpose, despite a lack of controlled evidence. We therefore conducted a study of the effects of the hookworm <i>Necator americanus</i> on patients with mild to moderately active Crohn9s. <h3>Methods</h3> Fifty-six patients with a Crohn9s disease activity index (CDAI) of 220–450 were randomised to receive 10 hookworm larvae or placebo (histamine) under a plaster patch on the forearm. Clinical activity and immunological changes were monitored over 12 weeks before hookworm was eradicated by treatment with mebendazole, and there was a final visit at 24 weeks. The primary analysis of effect was of the change from baseline at 12 weeks in the CDAI assessed by a generalised linear model (analysis of covariance) with change from baseline as response with terms for treatment arm and baseline CDAI as explanatory variables. Assuming a standard deviation of the change in the Crohn9s disease activity index of 110 this study of 56 patients had 80% power to detect a difference of 85 in the CDAI with hookworm treatment compared to control (α=0.05). <h3>Results</h3> Clean file was declared and the treatment code broken at 5 p, on 30 November 2009. Groups were well matched for age (mean 38.2±11.7 (SD) years for hookworm treatment, 42.2±13.2 for placebo), sex (50% vs 54% female), smoking, drug use and disease location. Preliminary analysis of the primary endpoint appeared to show a strong trend against any evidence of therapeutic benefit with hookworm. Patients treated with hookworm had a 64 point increase in CDAI (95% CIs ranging from a 15-point benefit to a 143-point deterioration). There was no obvious difference in advers events in each group. <h3>Conclusion</h3> Our preliminary analysis appears to exclude any significant overall benefit from treatment with 10 <i>Necator americanus</i> larvae in active Crohn9s Disease and raises the possibility that such treatment may even be harmful. Further analysis will be needed to determine whether apparent deteriorations in CDAI may reflect gastrointestinal symptoms induced by hookworm infection and whether there might be benefit in subgroups. Further work could explore whether different dosing regimens would be more successful.
Prognostic Implications of the Immunophenotype in Biphenotypic Acute Leukemia.
Authors: Je-Hwan Lee, Yoo-Hong Min, Chul Won Chung, Byoung Kook Kim, Hwi-Joong Yoon, Deog-Yeon Jo, Ho-Jin Shin, Soo-Mee Bang, Jong-Ho Won, Dae Young Zang, Hyeoung Joon Kim, Hyun-Sook Chi, Kyoo Hyung Lee, June-Won Cheong, Jin Seok Kim, Sun-Hee Kim, Seonyang Park, Su Yon Park, Jooseop Chung, Jae-Hoon Lee, Chan-Jeoung Park
Journal: Blood (2006)
335. High Content Analysis Platform for Optimization of Lipid Mediated CRISPR-Cas9 Delivery Strategies in Human Cells
Authors: Benjamin Steyer, Jared Carlson-Stevermer, Nicolas Angenent-Mari, Andrew Khalil, Ty Harkness, Krishanu Saha
Journal: Molecular Therapy (2016)

Background: Non-viral gene-editing of human cells using the CRISPR-Cas9 system requires optimized delivery of multiple components. Both the Cas9 endonuclease and a single guide RNA, that defines the genomic target, need to be present and co-localized within the nucleus for efficient gene-editing to occur. This work describes a new high-throughput screening platform for the optimization of CRISPR-Cas9 delivery strategies. Methods: By exploiting high content image analysis and microcontact printed plates, multi-parametric gene-editing outcome data from hundreds to thousands of isolated cell populations can be screened simultaneously. Employing this platform, we systematically screened four commercially available cationic lipid transfection materials with a range of RNAs encoding the CRISPR-Cas9 system. Analysis of Cas9 expression and editing of an endogenous and fluorescent mCherry reporter transgene within human embryonic cells was monitored over several days after transfection. Design of experiments analysis enabled rigorous evaluation of delivery materials and RNA concentration conditions. Results: The results of this analysis indicated that the concentration and identity of transfection material have significantly greater effect on gene-editing than ratio or total amount of RNA. Cell subpopulation analysis on microcontact printed plates, further revealed that low cell number and high Cas9 expression 24 hours after CRISPR-Cas9 delivery, were strong predictors of gene-editing outcomes. After purifying the population for high Cas9 expression, 24 hours after CRISPR-Cas9 delivery, greater than 92% of cells were properly edited. Significance: These results suggest design principles for the development of materials and transfection strategies with lipid-based materials. This platform could be applied to rapidly optimize materials for gene-editing in a variety of cell/tissue types in order to advance genomic medicine, regenerative biology and drug discovery.
An interdisciplinary early simultaneous palliative approach in metastatic non-small cell lung cancer: preliminary data in outpatient setting
Authors: A. Catino, D. Galetta, F. Aloè, A. Misino, M.E. Piccininno, A. Daniele, D. Ricci, A. Logroscino, C. Cormio
Journal: Annals of Oncology (2015)
Allogeneic Hematopoeitic Stem Cell Transplantation (AHSCT) Versus Hypomethylating Agents (HMA) in Patients (pts) with Myelodysplastic Syndrome (MDS): A Case-Control Study
Authors: Maria F Tanaka, Elias Jabbour, Hagop M. Kantarjian, Sherry Pierce, Richard Champlin, Marcos De Lima, Guillermo Garcia-Manero
Journal: Blood (2011)
Long-Term Outcome for De Novo Lymphoblastic Lymphoma (LL) After Frontline Therapy with Hyper-CVAD Regimen and Variants.
Authors: Deborah A. Thomas, Stefan Faderl, Susan O'Brien, William G. Wierda, Guillermo Garcia-Manero, Srdan Verstovsek, Marina Konopleva, Tapan Kadia, Steven M. Kornblau, Luis Fayad, Jorge Romaguera, Jorge E. Cortes, Hagop Kantarjian
Journal: Blood (2010)
Effect of High-Dose Rituximab on Peripheral Blood Stem Cell Mobilization in Intermediate Grade Non-Hodgkin’s Lymphomas.
Authors: Chitra Hosing, Rima M. Saliba, Martin Korbling, Sandra Acholonu, Safa Karandish, Sergio Giralt, Jo Lauppe, Marcos de Lima, Grace-Julia Okoroji, Daniel R. Couriel, Richard Champlin, Issa F. Khouri, Michele L. Donato
Journal: Blood (2004)
In Vivo Ischemia Detection by Luminescent Nanothermometers
Authors: Erving Clayton Ximendes, Uéslen Rocha, Blanca del Rosal, Alberto Vaquero, Francisco Sanz‐Rodríguez, Luis Monge, Fuqiang Ren, Fiorenzo Vetrone, Dongling Ma, José García‐Solé, Carlos Jacinto, Daniel Jaque, Nuria Fernández
Journal: Advanced Healthcare Materials (2016)

There is an urgent need to develop new diagnosis tools for real in vivo detection of first stages of ischemia for the early treatment of cardiovascular diseases and accidents. However, traditional approaches show low sensitivity and a limited penetration into tissues, so they are only applicable for the detection of surface lesions. Here, it is shown how the superior thermal sensing capabilities of near infrared-emitting quantum dots (NIR-QDs) can be efficiently used for in vivo detection of subcutaneous ischemic tissues. In particular, NIR-QDs make possible ischemia detection by high penetration transient thermometry studies in a murine ischemic hindlimb model. NIR-QDs nanothermometers are able to identify ischemic tissues by means of their faster thermal dynamics. In addition, they have shown to be capable of monitoring both the revascularization and damage recovery processes of ischemic tissues. This work demonstrates the applicability of fluorescence nanothermometry for ischemia detection and treatment, as well as a tool for early diagnosis of cardiovascular disease.
Impact of Examined Lymph Node Count on Precise Staging and Long-Term Survival of Resected Non–Small-Cell Lung Cancer: A Population Study of the US SEER Database and a Chinese Multi-Institutional Registry
Authors: Wenhua Liang, Jiaxi He, Yaxing Shen, Jianfei Shen, Qihua He, Jianrong Zhang, Gening Jiang, Qun Wang, Lunxu Liu, Shugeng Gao, Deruo Liu, Zheng Wang, Zhihua Zhu, Calvin S.H. Ng, Chia-chuan Liu, René Horsleben Petersen, Gaetano Rocco, Thomas D’Amico, Alessandro Brunelli, Haiquan Chen, Xiuyi Zhi, Bo Liu, Yixin Yang, Wensen Chen, Qian Zhou, Jianxing He
Journal: Journal of Clinical Oncology (2017)

Purpose We investigated the correlation between the number of examined lymph nodes (ELNs) and correct staging and long-term survival in non–small-cell lung cancer (NSCLC) by using large databases and determined the minimal threshold for the ELN count. Methods Data from a Chinese multi-institutional registry and the US SEER database on stage I to IIIA resected NSCLC (2001 to 2008) were analyzed for the relationship between the ELN count and stage migration and overall survival (OS) by using multivariable models. The series of the mean positive LNs, odds ratios (ORs), and hazard ratios (HRs) were fitted with a LOWESS smoother, and the structural break points were determined by Chow test. The selected cut point was validated with the SEER 2009 cohort. Results Although the distribution of ELN count differed between the Chinese registry (n = 5,706) and the SEER database (n = 38,806; median, 15 versus seven, respectively), both cohorts exhibited significantly proportional increases from N0 to N1 and N2 disease (SEER OR, 1.038; China OR, 1.012; both P &lt; .001) and serial improvements in OS (N0 disease: SEER HR, 0.986; China HR, 0.981; both P &lt; .001; N1 and N2 disease: SEER HR, 0.989; China HR, 0.984; both P &lt; .001) as the ELN count increased after controlling for confounders. Cut point analysis showed a threshold ELN count of 16 in patients with declared node-negative disease, which were examined in the derivation cohorts (SEER 2001 to 2008 HR, 0.830; China HR, 0.738) and validated in the SEER 2009 cohort (HR, 0.837). Conclusion A greater number of ELNs is associated with more-accurate node staging and better long-term survival of resected NSCLC. We recommend 16 ELNs as the cut point for evaluating the quality of LN examination or prognostic stratification postoperatively for patients with declared node-negative disease.
Abstract 341: Breast cancer cell adhesion and degradome interact to drive metastasis
Authors: Asif Rizwan, Menglin Cheng, Zaver M. Bhujwalla, Balaji Krishnamachary, Lu Jiang, Kristine Glunde
Journal: Cancer Research (2015)

Abstract Although primary breast tumors are detected early in most cases, it is inevitable that many patients remain at risk for future recurrence and death due to micrometastases. We investigated the metastatic process with a focus on matrix metalloproteases (MMPs) within the degradome and on integrins and E-cadherin within the adhesome. We have performed comparative studies with a set of non-metastatic (BT-474, T47D, MCF7) versus metastatic (MDA-MB-231, SUM149, SUM159) human breast cancer cell lines and xenografts. Experiments were performed to measure growth rate, migration, invasion, and colony formation. Immunoblotting and immunohistochemistry revealed a higher expression of MMPs and heterophilic cell adhesion molecules integrin β1 and lower expression of homophilic cell adhesion molecule E-cadherin in the metastatic tumor cells and xenografts. Using zymography and activatable fluorescent probes for noninvasive imaging of MMPs, we demonstrated that metastatic breast cancer cells and tumors displayed an elevated degradome activity as compared to non-metastatic cells and tumors. Cell adhesion and cell aggregation assays showed an increased heterophilic and decreased homophilic adhesion in the metastatic models. Inhibiting MMPs reduced the expression of integrin β1, and stimulating integrin β1 resulted in higher MMP activities in metastatic cells. Re-expression of E-cadherin in metastatic cells led to a reduced expression of active integrin β1. Finally, circulating breast cancer cells and cells from lung metastatic nodules generated from metastatic tdTomato-fluorescing breast cancer cells displayed a reduced expression of active integrin β1 and less epithelial-mesenchymal-transition (EMT) marker protein S100A4. Our results indicate that proteolytic ECM remodeling by MMPs and cell adhesion by integrin β1 and E-cadherin are interdependent processes that control transformation from benign to invasive carcinoma and are critical for metastasis. Citation Format: Asif Rizwan, Menglin Cheng, Zaver M. Bhujwalla, Balaji Krishnamachary, Lu Jiang, Kristine Glunde. Breast cancer cell adhesion and degradome interact to drive metastasis. [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 341. doi:10.1158/1538-7445.AM2015-341
Assessment of a cell-line-derived HIF1α gene signature in tumor tissue from a metastatic renal cell carcinoma (RCC) trial of pazopanib.
Authors: Robert C. Gagnon, Yuan Liu, Toni K. Choueiri, Anne-Marie Martin, Jonathan E. Rosenberg, Sabina Signoretti, Lini N. Pandite
Journal: Journal of Clinical Oncology (2012)

408 Background: Microarray and clinical data from a randomized phase II RCC clinical trial were evaluated to examine the HIF1α kidney cancer gene signature developed from cell lines by Shen et al (Cancer Discovery 2011). Methods: Archival FFPE tumor samples were collected from patients (pts) enrolled in a Phase II RCC study of pazopanib (Hutson, JCO 2009). RNA was isolated and microarray analysis was performed at Response Genetics, Inc. (Los Angeles, CA) using the Affymetrix (Affy) U133 plus Array. Affy data were normalized using the MAS5 algorithm. Genes (n=69) identified from experiments in 10 cancer cell lines were mapped to genes on the U133 array. Patterns of expression (exp) among the mapped genes were assessed using multivariate analyses. Putative patterns were assessed for association with HIF1α gene exp levels, and both patterns and HIF1α levels were assessed for association with response rate (RR) (RECIST), and PFS, using nonparametric and Kaplan-Meier analyses. Gene set enrichment analysis (GSEA) was applied to determine if mapped genes were enriched for HIF1α gene exp. Results: RNA was available for 46 of 225 patients; baseline characteristics were similar to the overall study. 41/46 patients had VHL heterozygous mutations; 5/46 patients were VHL wild type. HIF1a gene expression was detected in all 46 patients. 64/69 genes were mapped to the Affy platform. For genes which mapped to multiple probes, the probe closest to the 3` end was used. A potential 4 cluster pattern was identified. These clusters were associated with HIF1α gene exp, but neither clusters nor HIF1α gene exp were associated with clinical response to pazopanib. Conclusions: The observed pattern of gene exp among 46 pts with available data from a Phase II RCC study of pazopanib is consistent with the cell line derived gene set proposed by Shen et al. Patterns are associated with HIF1α exp; neither patterns nor HIF1α exp are associated with clinical response in this small subset of pts. These data support the on-going efforts in bench-to-bedside research.
Dynamic Pattern of Adhesion Receptor Expression during the Maturation of Ex-Vivo Generated Human Adult and Neonatal Erythroid Cells.
Authors: Giovanni Migliaccio, Massimo Sanchez, Francesca Masiello, Valentina Tirelli, Katija Iliecic, Annalisa Mancini, Paul S. Frenette, Anna Rita Migliaccio
Journal: Blood (2008)
Abstract 4495: Small molecule approach for targeting tumor-associated macrophages via a functional FRβ
Authors: Leroy W. Wheeler, Yingjuan Lu, Vicky Cross, Alex Lloyd, Nikki Parker, Longwu Qi, Kevin Wang, Ian Wang, Spencer Hahn, Jeremy Vaughn, Iontcho P. Vlahov, Philip S. Low, Christopher P. Leamon
Journal: Cancer Research (2015)

Abstract Tumor-associated macrophages (TAMs) are considered an attractive target for oncotherapy because of their important role in tumor microenvironment. While TAMs mostly arise from inflammatory blood monocytes, they become quickly programmed to the pro-tumor phenotype. In response to tumor-derived factors, these M2-biased TAMs are essentially tumor helper cells, as both cancer cells and TAMs promote each another through a paracrine signaling loop involving epidermal growth factor and colony stimulating factor-1. This important cellular interaction is critical at all stages of tumor progression including angiogenesis, invasion, growth and metastasis. In recent years, TAMs (CD68+, CD163+) have been found to express a functional folate receptor-β (FRβ) that displays high-affinity ligand binding and subsequent ligand-initiated endocytosis. FRβ-expressing TAMs are present in various cancer subtypes, the perivascular region, and the tumor invasive front. The abundance of FRβ+ TAMs has been linked to poor patient survival in pancreatic ductal adenocarcinoma. In the present study, we first characterized the phenotype of FRβ+ TAMs ex-vivo from both syngeneic and xenographic tumor models (breast, lung, melanoma, and pancreatic cancers). Using thioglycollate-elicited macrophages as positive controls, we estimated FRβ levels on TAMs with monoclonal antibodies and functional folate ligands. Using a ligand conjugation approach, we focused on targeting FRβ+ TAMs in tumors arising from cancer cells that do not express functional FR themselves. Preliminary proof-of-concept was established in the highly aggressive FR-negative 4T1 mammary tumor with a folate-targeted DNA alkylating agent. In addition, immunohistochemical analysis showed high FRβ expression in human anaplastic thyroid cancer, a TAM-rich disease with very poor prognosis. Collectively, our data suggest that targeting a TAM-rich cancer via FRβ may be a viable therapeutic approach with potential applications in FR-negative tumors. Citation Format: Leroy W. Wheeler, Yingjuan Lu, Vicky Cross, Alex Lloyd, Nikki Parker, Longwu Qi, Kevin Wang, Ian Wang, Spencer Hahn, Jeremy Vaughn, Iontcho P. Vlahov, Philip S. Low, Christopher P. Leamon. Small molecule approach for targeting tumor-associated macrophages via a functional FRβ. [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 4495. doi:10.1158/1538-7445.AM2015-4495
Histological subtype analysis of colon cancer: a population-based study. Is mucinous carcinoma a different disease? What clinical dilemma
Authors: A. De Giorgi, F. Negri, E.M. Silini, P. Sgargi, A. Gilli, M. Michiara, C. Azzoni, L. Bottarelli, C. Pinto
Journal: Annals of Oncology (2015)
Supervised injection centers could save millions of dollars in health costs, US study finds
Authors: Michael McCarthy
Journal: BMJ (2016)

Opening a supervised injection facility, where drug users can inject drugs under medical supervision, could save US cities millions of dollars in health related costs each year, a study has found.

These facilities reduce injection related infections and prevent overdose deaths, said senior author Alex Kral, epidemiologist and director of the Behavioral and Urban Health Program at RTI International, a non-profit research institution in North Carolina.1 There are 66 injections centers in 11 countries, but none in the US. “The goal of our study was to …