tbuckley/cabot-search huggingface dataset:
PTH-091 Is the diagnosis of coeliac disease associated with socio-economic status? A population-based study: Abstract PTH-091
Authors: N R Lewis, R F A Logan, D S Sanders, J West
Journal: Gut (2010)

<h3>Introduction</h3> The rate of diagnosis of coeliac disease in developed countries has increased dramatically since the introduction of serological tests without an obvious environmental precipitant. Little is known about the socio-economic distribution of coeliac disease; there is some evidence that it is less common in more deprived social groups.1 We quantified the incidence of new diagnoses of coeliac disease by socio-economic status in a large, contemporary and population-based cohort. <h3>Methods</h3> The postcode of residence at diagnosis in consecutive incident adult cases of coeliac disease (n = 837) between January 2000 and December 2006 at Nottingham University Hospital and Royal Hallamshire Hospital was used to determine the Index of Multiple Deprivation 2007 (IMD07) score.2 Incidence rates were calculated using the total adult population for Sheffield and Nottingham derived from UK 2001 National Census categorised into corresponding IMD07 quintiles and Poisson models were fitted. <h3>Results</h3> There was a strong, independent graded association between the incidence rate of new diagnoses of coeliac disease and socio-economic status. The incidence rate of coeliac disease was twice as high for the least deprived quintile (age- and sex-adjusted IRR* 1.93, 95% CI 1.61 to 2.44) compared with the most deprived quintile. Socio-economic status in incident coeliac disease was not associated with more severe coeliac disease (OR for quintile V to quintile I for presence of malabsorption 1.04, 95% CI 0.47 to 2.28; and for Marsh 3b, 3c histological change OR 0.87, 95% CI 0.56 to 1.34) (Abstract 091). <h3>Conclusion</h3> The rate of new diagnoses of coeliac disease was twice as high in people from affluent areas compared with that in people living in poorer areas. This striking difference could be due to variation in environmental exposures such as breastfeeding practices3 or could be accounted for by differences in uptake and utilisation of health services.
Safety and Efficacy of Cytotoxic Chemotherapy after Allogeneic Hematopoietic Stem Cell Transplantation for Relapsed Hematologic Malignancy.
Authors: Nancy M. Hardy, Jeanne Odom, Kelly Snow, Robert Dean, Steven Pavletic, Claude Sportes, Ronald Gress, Daniel H. Fowler, Michael R. Bishop
Journal: Blood (2006)
An Inhibitor of TGF-β Promotes Proliferation of Normal but Not MPN Hematopoietic Cells and Is a Candidate Therapeutic Agent for the Treatment of MPN Patients Carrying JAK2 V617F or Calr pQ365fs Mutations
Authors: Anna Rita Migliaccio, Camelia Iancu-Rubin, Rona Singer Weinberg, Ronald Hoffman, Amylou Constance Dueck, John O. Mascarenhas
Journal: Blood (2015)
White Scale Sign for Xeroderma
Authors: Amrei Klemmer, Florian Anzengruber, Dmitry Kazakov, Alexander A. Navarini
Journal: JAMA Dermatology (2016)

Results | The survey yielded an estimated 85% response rate, with 204 patients out of an estimated 240 patients agreeing to participate.The population was 56.37% male and 43.63% female with no statistically significant difference, and 62.25% of participants had a college degree or higher level of education.The highest ranked notification preferences were the online portal (59.40%) and telephone call (48.95%).About 54% of patients reported their preference would change depending on whether biopsy results were normal or abnormal (P < .001).For a normal skin biopsy result, most patients (n = 143) reported a preference for an online portal (55.20%).For abnormal results, most patients (n = 145) indicated a preference for a telephone call (69.2%).Among participants with previous online portal experience, 52.05% indicated a preference for online portals.Of the participants who did not have experience using online portals, 61.11% indicated a preference for a telephone call; χ 2 tests suggested a correlation between age and online portal experience, as well as age and online portal notification preference (P = .05).Most participants ranked depth of information received (44.78%) and amount of time to discuss results (35.82%) as their most important factors for selecting a notification modality when receiving abnormal results.Other demographic data did not significantly influence ranking of preferred factors for being notified of abnormal results.Patients who indicated that they preferred a quicker method of skin biopsy result notification did not differ based on history of skin biopsies or skin cancers.However, the odds of patients with online portal experience preferring a quicker method was statistically significant (Table ).Discussion | Our findings support that online portals are the most preferred method of skin biopsy result disclosure among patients, particularly when results are normal.Patients reported that amount of information and time to discuss results were their most important factors for choosing a modality for receiving abnormal results.In addition, the odds of patients with online portal experience preferring a quicker notification method was significant.There were study limitations that warrant discussion.We had a small sample size.Our location in a metropolitan area and large percentage of participants with college degrees or higher education may not be representative of other communities in the United States.We also did not collect demographic information regarding participant racial/ ethnic group.
Abstract LB-141: Specific and potent silencing of K-Ras by asymmetric silencing RNA (aiRNA) reveals addiction of cancer stem cells to mutant K-Ras amplification
Authors: Jun Oishi, Hiroki Umehara, Nithya Jesuraj, Jelena Barbulovic, Xiangao Sun, Chiang J. Li
Journal: Cancer Research (2015)

Abstract K-Ras, the first oncogene identified in human cancer, is mutated in about 30% of human solid tumors. K-Ras protein, a small membrane-bound GTP-binding protein, acts as a molecular switch to transduce cell proliferation signals. Activating mutations of K-Ras lock the Ras protein into the hyper-active GTP-bound state, resulting in the activation of numerous signaling pathways that control cell survival and proliferation. Ras is also an important oncoprotein in many cancers where it is not mutated since Ras can be functionally activated through aberrant activation of other signal transduction elements. Activated K-Ras proteins are, therefore, found in a large proportion of all human cancers, and occupy a central position of interest. Hypermalignant cancer cells, termed cancer stem cells (CSCs), that are highly tumorigenic and metastatic have been isolated from cancer patients with a variety of tumor types and found to have high stemness properties. These stemness-high cancer cells are hypothesized to be fundamentally responsible for cancer metastasis and relapse. Furthermore, a number of stemness genes, such as beta-catenin, nanog, Sox2, Oct3/4 have been implicated in cancer cell stemness. The role of oncogenes such as K-Ras in cancer cell stemness, however, is not clear. To elucidate the role of K-Ras in the maintenance of cancer cell stemness, we employed asymmetric silencing RNA technology (aiRNA) which is able to silence target genes with high potency and precision. Moreover, aiRNA technology can be readily applied to CSCs. Here we report, to our surprise, that CSCs are not simply addicted to activating mutations of K-Ras, or activation of downstream regulators of the Ras pathway. However, CSCs with amplified mutant K-Ras are highly sensitive to K-Ras silencing. Moreover, the DNA copy number of the mutant K-Ras directly predicts the sensitivity of CSCs to K-Ras silencing. Our studies suggest that amplified mutated K-Ras is required for the maintenance of malignancy and cancer cell stemness, which may have significant implications for understanding the connections between oncogenes and cancer cell stemness, and for developing cancer stem cell inhibitors. Citation Format: Jun Oishi, Hiroki Umehara, Nithya Jesuraj, Jelena Barbulovic, Xiangao Sun, Chiang J. Li. Specific and potent silencing of K-Ras by asymmetric silencing RNA (aiRNA) reveals addiction of cancer stem cells to mutant K-Ras amplification. [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 LB-141. doi:10.1158/1538-7445.AM2015-LB-141
Up-Front Window Trial of Gemtuzumab Ozogamicin (GO) in Previously Untreated Elderly Patients with AML: An EORTC Leukemia Group Study.
Authors: Sergio Amadori, S. Suciu, R. Willemze, F. Mandelli, D. Selleslag, R. Stauder, A. Ho, C. Denzlinger, G. Leone, G. Fillet, P. Muus, F. Beeldens, O. Anak, T. De Witte
Journal: Blood (2004)
The Multikinase Inhibitor Sorafenib Inhibts Proliferation in B- and T-Lymphoblastic Cell Lines Via the PI3K/Akt Pathway.
Authors: Catrin Schult, Meike Dahlhaus, Sonja Boldt, Änne Glass, Sabine Ruck, Mandy Sawitzky, Sandra Lange, Francesca Amoroso, Mathias Freund, Luca Maria Neri, Christian Junghanss
Journal: Blood (2008)
561. CRISPR-Induced Deletion (CinDel) Method Allows Permanent and Efficient Restoration of the DMD Gene Reading Frame in Duchenne Patient Myoblasts and Preserves Truncated Dystrophin Structure
Authors: Jean-Paul Iyombe-Engembe, Dominique L. Ouellet, Xavier Barbeau, Joël Rousseau, Pierre Chapdelaine, Patrick Lagüe, Jacques P. Tremblay
Journal: Molecular Therapy (2016)

The CRISPR/Cas9 system is a great revolution in biology. This technology allows the modification of genes in vitro and in vivo in a wide variety of living organisms. In most Duchenne Muscular Dystrophy (DMD) patients, expression of dystrophin (DYS) protein is disrupted because exon deletions result in a frame shift. Here we present CRISPR-induced deletion (CinDel), a new gene therapy approach to correct the DMD gene in Duchenne patients with one or more exons deletions. By using adequate pair of gRNAs targeting specifically the exons precede and follow the patient deletion in DMD gene, CinDel induces precise DSB in targeted sequences and allows an additional deletion. The remaining parts of the exons were fusioned by NHEJ to form a hybrid exon and restored the DMD reading frame in 62 % of hybrid exons in vitro in patient myoblasts and in vivo in electroporated muscle hDMD/mdx mice. Moreover, adequate pairs of gRNAs also restored the normal spectrin-like repeat of the dystrophin rod domain; such restoration is not obtained by exon skipping or deletion of complete exons. The expression of an internally deleted dystrophin protein was detected following the formation of myotubes by the unselected treated DMD myoblasts. Given that CinDel induces permanent reparation of the DMD gene this treatment would not have to be repeated as it is the case for exon skipping induced by oligonucleotides.
Phase II study of low-dose paclitaxel with timed thoracic radiotherapy (TTR) followed by gemcitabine and carboplatin consolidation in patients with unresectable stage III non-small cell lung cancer (NSCLC): NCT 00449657.
Authors: J. Zhang, S. M. Russo, H. A. Gay, T. Parent, Z. Nelson, S. Eubanks, P. R. Walker
Journal: Journal of Clinical Oncology (2011)

7044 Background: Concurrent chemoradiotherapy (CRT) is a curative potential treatment for unresectable stage III NSCLC, yet the optimal treatment paradigm and choice of regimen is unclear. Previous phase I/II study (Chen et al Clin Can Res 9:969-975, 2003) using low-dose paclitaxel with timed thoracic radiotherapy (TTR) has shown high local response by inducing maximum radiosensitization through G2-M cell cycle arrest. We conducted a phase II study of low-dose paclitaxel with TTR as induction, followed by systemic adjuvant full-dosing chemotherapy for unresectable stage III NSCLC patients. Methods: From 4/2007 to 12/2009, 30 patients with unresectable stage III NSCLC and ECOG PS 0-2 were enrolled. Patients received paclitaxel 15mg/m2 IV over 1 hour at 8am on Monday/Wednesday/Friday with total 55Gy TTR delivered at 4pm Monday/Wednesday/Friday and 8am Tuesday/Thursday over 5 weeks, followed by Carboplatin (AUC 5) day 1 and gemcitabine 1000mg/m2 IV days 1 and 8, q21d for 4 cycles. Primary end point was overall survival (OS); secondary end points were overall response rate (ORR), progression-free survival (PFS) and toxicities. Results: 27 pts were evaluable. Patient characteristics: M 70%; median age 67 (39-82), 41% over age 70; stage IIIB 56%. 30 month OS 28% (95% CI: 15-53); 30 month PFS 20% (95% CI: 9-44). ORR was 63%, 6 CR, 11 PR, 6 SD, 1 PD. TTR was delivered as planned in 26/27 patients (1 pt died after 3rd week TTR). TTR related grade 3 toxicities: esophagitis 2, pneumonitis 1, neutropenia 1. CT consolidation related grade 3/4 toxicities: pneumonitis 6, cytopenias 7, esophagitis 2, which limited median delivery of CT to 2 cycles. One patient died of sepsis. 2 patients developed pulmonary embolism. Conclusions: Low-dose paclitaxel with timed thoracic radiotherapy is an effective concurrent CRT regimen with minimal toxicity in nonsurgical stage III NSCLC patients, especially the elderly population. Gemcitabine radiation recall and hematological toxicity were limiting adjuvant CT dose delivery.
Safety and efficacy trial of preoperative sequential chemo-radiation therapy for the surgery sparing treatment (SST) in early breast cancer (EBC): Japan Clinical Oncology Group trial (JCOG0306)
Authors: H. Mukai, T. Watanabe, M. Mitsumori, H. Tsuda, S. Nakamura, N. Masuda, T. Asaga, N. Yamamoto, H. Kaba, K. Aogi
Journal: Journal of Clinical Oncology (2006)

10717 Background: The combination of preoperative anthracycline-containing regimen and taxane can obtain a pathological complete response (pCR) rate of around 30% for patients (pts) with EBC. To pursue higher pCR rate with maintaining good systemic control is necessary to put the SST practical in the future. The objective of this trial was to determine whether the addition of radiation therapy (RT) to chemotherapy (CT) could surpass the pCR rate of 50% in pts with EBC. Methods: We conducted a safety and efficacy trial of CT (4 courses of doxorubicin and cyclophosphmide (60/600 mg/m 2 ) followed by 12 courses of weekly paclitaxel (80 mg/m 2 ) and RT (whole breast 45Gy + boost 10Gy) sequentially as a primary therapy in pts with stage I-IIIA (5.0 cm ≥ tumor size ≥ 2.0 cm) BC. All pts received mastectomy or lumpectomy 12–16 weeks after completion of RT to maximize the effect of RT. pCR was assessed by the central pathological review board according to the pCR classification adopted by the National Surgical Adjuvant Breast and Bowel Project (NSABP). The study was designed to enroll 104 eligible pts with threshold pCR 35%, expected pCR 50%, alpha 0.05, beta 0.1, and additionally to have the width of 95% confidence interval (CI) within ±10% for sufficient precision of pCR. Results: Between June 2004 and April 2005, 108 pts were enrolled in this trial. Median age was 50 years (range 23–69). 1 pt had T1, 95 T2, and 3 T3 tumors (2 pts’ data are missing and 7 pts’ data have not been collected). 58% (59/101) were ER+, 49% (49/101) were PgR+ and 31% (31/101) had HER2 overexpression. Based on the planned interim analysis, the Data Monitoring Committee recommended to terminate the trial for insufficient pCR rate of the first 7 eligible patients (0% (0/7), 95% CI: 0–41.0%). Toxicities were within expected range. Conclusions: Preoperative sequential chemo (AC followed by paclitaxel) -radiation therapy is not considered to be promising for accomplishing enough pCR rate. No significant financial relationships to disclose.
A novel class of apical sodium--dependent bile salt transporter inhibitors: 1-(2,4-bifluorophenyl)-7-dialkylamino-1,8-naphthyridine-3-carboxamides
Authors: Hongtao Liu, Guoxun Pang, Jinfeng Ren, Yue Zhao, Juxian Wang
Journal: Acta Pharmaceutica Sinica B (2016)

The apical sodium--dependent bile acid transporter (ASBT) is the main transporter to promote re-absorption of bile acids from the intestinal tract into the enterohepatic circulation. Inhibition of ASBT could increase the excretion of bile acids, thus increasing bile acid synthesis and consequently cholesterol consumption. Therefore, ASBT is an attractive target for developing new cholesterol-lowering drugs. In this report, a series of 1-(2,4-bifluorophenyl)-7-dialkylamino-1,8-naphthyridine-3-carboxamides were designed as inhibitors of ASBT. Most of them demonstrated potency against ASBT transport of bile acids. In particular, compound 4a1 was found to have the best activity, resulting in 80.1% inhibition of ASBT at 10 μmol/L.
The Use of 2nd generation Tyrosine Kinase Inhibitors (TKI) after Failure to 2 Prior TKI: Long-Term Follow-up.
Authors: Ravi n Jain Garg, Hagop M Kantarjian, Susan O’Brien, Alfonso Quintas-Cardama, Stefan Faderl, Zeev Estrov, Jorge Cortes
Journal: Blood (2008)
Promiscuous Antigen Reactivity May Underlie Clinical Aggressiveness and Increased Risk for Richter's Syndrome in Chronic Lymphocytic Leukemia with Stereotyped IGHV4-39/IGKV1(D)-39 B Cell Receptors
Authors: Maria Gounari, Stavroula Ntoufa, Charles C. Chu, Athanasios Tsaftaris, Nicholas Chiorazzi, Kostas Stamatopoulos, Paolo Ghia
Journal: Blood (2012)
Bortezomib- and Thalidomide-Induced Peripheral Neuropathy (PN) in Multiple Myeloma (MM): Clinical and Molecular Analysis of 474 Patients Treated with Thalidomide-Dexamethasone (TD) or Bortezomib-TD (VTD)
Authors: Paola Tacchetti, Carolina Terragna, Gioacchino Catania, Magda Marcatti, Andrea Nozza, Felicetto Ferrara, Francesco Nobile, Catello Califano, Anna Baraldi, Andrea Gallamini, Pellegrino Musto, Patrizia Tosi, Piero Galieni, Annalisa Pezzi, Francesco Lanza, Michela Ceccolini, Filippo Ballerini, Lucio Catalano, Clotilde Cangialosi, Antonio Lazzaro, Giorgio Paladini, Ruggero Mozzana, Beatrice Anna Zannetti, Graziella Pinotti, Francesca Elice, Michele Baccarani, Mario Boccadoro, Guido Cavaletti, Michele Cavo
Journal: Blood (2011)
Imatinib in the Treatment of CML Patients ≥ 65 Years Old in Late Chronic Phase: Results of a Phase II Study of the GIMEMA CML Working Party.
Authors: Simona Bassi, Fausto Castagnetti, Marilina Amabile, Barbara Giannini, Daniela Cilloni, Barbara Izzo, Antonio De Vivo, Simona Luatti, Nicoletta Testoni, Giovanna Rege-Cambrin, Ilaria Iacobucci, Enrico Gottardi, Fabrizio Pane, Francesco Salvatore, Alessandra Dorigo, Giuseppe Saglio, Giovanni Martinelli, Gianantonio Rosti, Michele Baccarani
Journal: Blood (2004)
Abstract LB-295: Analysis of miR-21 isomiRs in lung cancer
Authors: Jennie D. Leikin, Adriana Zingone, Derek Brown, Khadijah Mitchell, Mohammed Khan, Oscar Vidal, Brid Ryan
Journal: Cancer Research (2015)

Abstract microRNAs (miRNA) are small non-coding RNAs that target mRNA transcripts. Primarily, they bind to the 3′UTR of mRNA sequences and repress protein translation. They are involved in the regulation of over 60% of human genes. miRNAs are deregulated in cancer and expression signatures have been correlated with cancer diagnosis, progression and prognosis. Thus, they are being pursued for clinical application. isomiRs, or miRNA variants that are generated post-transcriptionally, were originally classified as experimental error in cloning and next generation sequencing studies. However, over the past five years it has become increasingly clear that isomiRs are evolutionarily conserved, prevalent and functional. miR-21 is overexpressed and associated with poor prognosis in multiple malignancies and as such it is currently under development as a therapeutic target. Thus, we examined the isomiR landscape of miR-21 in lung cancer using data from The Cancer Genome Atlas (lung adenocarcinoma n = 420 and squamous cell carcinoma n = 296). Raw sequence files were extracted from TCGA, cleaned and analyzed using STATA 13. We observed that there are significantly more isomiRs of miR-21 in both lung adenocarcinoma (LUAD) and squamous cell carcinoma (LUSC) compared to non-involved adjacent lung tissue. Specifically, LUAD had total of 244 5p variants and LUSC had 232 5p variants, compared with 74 and 105 in non-involved tissue, respectively. The most prevalent isomiR of miR-21 was not the canonical ‘miRBase’ isomiR and the most common edit was a 5′ deletion with 3′ addition. There were 15 miR-21-5p isomiRs in LUAD and 12 in LUSC that were prevalent (defined as detected in more than 50% of patients) and were expressed at a significantly higher level defined as detected with a FPKM value greater than 50) in tumor versus non-involved tissue samples. The average fold change was 5.7 in LUAD (range 2.8-21.1) and 2.7 in LUSC (range 1.7-5.6). Of the prevalent miR-21-5p isomiRs, 6 in LUAD and 4 in LUSC had a change in the canonical miR-21 seed sequence. An analysis of the targets of these isomiRs using the target prediction algorithms Targetscan and Diana revealed limited overlap in gene targets (0% to 54%) compared with canonical miR-21-5p targets. Our work highlights a high complexity of miRNA sequence heterogeneity in lung cancer. Combining the characterization of miR-21 isomiRs and pursuing translational laboratory studies will allow us to determine the functionality of these isomiRs and their relevance for human cancer diagnosis and treatment. Citation Format: Jennie D. Leikin, Adriana Zingone, Derek Brown, Khadijah Mitchell, Mohammed Khan, Oscar Vidal, Brid Ryan. Analysis of miR-21 isomiRs in lung 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 LB-295. doi:10.1158/1538-7445.AM2015-LB-295
Neurological Injury and Cerebral Blood Flow in Single Ventricles Throughout Staged Surgical Reconstruction
Authors: Mark A. Fogel, Christine Li, Okan U. Elci, Tom Pawlowski, Peter J. Schwab, Felice Wilson, Susan C. Nicolson, Lisa M. Montenegro, Laura Diaz, Thomas L. Spray, J. William Gaynor, Stephanie Fuller, Christopher Mascio, Marc S. Keller, Matthew A. Harris, Kevin K. Whitehead, Jim Bethel, Arastoo Vossough, Daniel J. Licht
Journal: Circulation (2016)

Patients with a single ventricle experience a high rate of brain injury and adverse neurodevelopmental outcome; however, the incidence of brain abnormalities throughout surgical reconstruction and their relationship with cerebral blood flow, oxygen delivery, and carbon dioxide reactivity remain unknown.Patients with a single ventricle were studied with magnetic resonance imaging scans immediately prior to bidirectional Glenn (pre-BDG), before Fontan (BDG), and then 3 to 9 months after Fontan reconstruction.One hundred sixty-eight consecutive subjects recruited into the project underwent 235 scans: 63 pre-BDG (mean age, 4.8±1.7 months), 118 BDG (2.9±1.4 years), and 54 after Fontan (2.4±1.0 years). Nonacute ischemic white matter changes on T2-weighted imaging, focal tissue loss, and ventriculomegaly were all more commonly detected in BDG and Fontan compared with pre-BDG patients (P<0.05). BDG patients had significantly higher cerebral blood flow than did Fontan patients. The odds of discovering brain injury with adjustment for surgical stage as well as ≥2 coexisting lesions within a patient decreased (63%-75% and 44%, respectively) with increasing amount of cerebral blood flow (P<0.05). In general, there was no association of oxygen delivery (except for ventriculomegaly in the BDG group) or carbon dioxide reactivity with neurological injury.Significant brain abnormalities are commonly present in patients with a single ventricle, and detection of these lesions increases as children progress through staged surgical reconstruction, with multiple coexisting lesions more common earlier than later. In addition, this study demonstrated that BDG patients had greater cerebral blood flow than did Fontan patients and that an inverse association exists of various indexes of cerebral blood flow with these brain lesions. However, CO2 reactivity and oxygen delivery (with 1 exception) were not associated with brain lesion development.URL: http://www.clinicaltrials.gov. Unique identifier: NCT02135081.