tbuckley/cabot-search huggingface dataset:
Association Between Rosacea and Parkinson Disease
Authors: Athanasia Alexoudi, Iliana Alexoudi, Stylianos Gatzonis
Journal: JAMA Neurology (2016)

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Clinical and Genetic Risk Assessment for Overall Survival in Haematopoietic Stem Cell Transplantation (HSCT).
Authors: Anne M Dickinson, Kim F Pearce, Graham H Jackson, Matthew Collin, Jean Norden, Ernst Holler, Heike Bickeboller, Yesilda Balavarca, Vanderson Rocha, Hans-Jochem Kolb, Alvaro Aubano, Ilona Hromadnikova, Petr Sedlacek, Alois Gratwohl
Journal: Blood (2009)
Topical delivery of low-cost protein drug candidates made in chloroplasts for biofilm disruption and uptake by oral epithelial cells
Authors: Yuan Liu, Aditya C. Kamesh, Yuhong Xiao, Victor Sun, Michael Hayes, Henry Daniell, Hyun Koo
Journal: Biomaterials (2016)

Protein drugs (PD) are minimally utilized in dental medicine due to high cost and invasive surgical delivery. There is limited clinical advancement in disrupting virulent oral biofilms, despite their high prevalence in causing dental caries. Poor efficacy of antimicrobials following topical treatments or to penetrate and disrupt formed biofilms is a major challenge. We report an exciting low-cost approach using plant-made antimicrobial peptides (PMAMPs) retrocyclin or protegrin with complex secondary structures (cyclic/hairpin) for topical use to control biofilms. The PMAMPs rapidly killed the pathogen Streptococcus mutans and impaired biofilm formation following a single topical application of tooth-mimetic surface. Furthermore, we developed a synergistic approach using PMAMPs combined with matrix-degrading enzymes to facilitate their access into biofilms and kill the embedded bacteria. In addition, we identified a novel role for PMAMPs in delivering drugs to periodontal and gingival cells, 13-48 folds more efficiently than any other tested cell penetrating peptides. Therefore, PDs fused with protegrin expressed in plant cells could potentially play a dual role in delivering therapeutic proteins to gum tissues while killing pathogenic bacteria when delivered as topical oral formulations or in chewing gums. Recent FDA approval of plant-produced PDs augurs well for clinical advancement of this novel concept.
Structured outpatient palliative care family conferences to enhance early integration of palliative care in advanced cancer.
Authors: Cheruppolil R. Santhosh-Kumar, Deborah Gray, Stephanie Struve, Carol Huibregtse
Journal: Journal of Clinical Oncology (2015)

36 Background: Integrating early palliative care with cancer treatment improves quality of life and survival. Effective communication among physicians, patients and their loved ones is crucial to end-of-life, hospice and palliative care discussions. To address the inherent challenges in these discussions, we implemented a structured outpatient palliative care family conference (OFC) program at our community cancer clinic. Methods: A team comprising a hematologist/oncologist, cancer nurse navigator and social worker developed a toolkit for conducting an OFC, recognizing that each family conference is a unique adaptive challenge. New patients with advanced malignancies and limited life expectancy (&lt;12 months) were offered a 90-minute structured OFC attended by the care team, patient and family members and or friends. Pre and post-conference patient satisfaction surveys and other data were collected prospectively. Results: From March 2014 through May 2015, fortyOFC were conducted (16 female and 24 male patients, median age: 67 years). Diagnoses were advanced gastrointestinal (14), lung (12), hematologic (6) and other (8) malignancies. As a direct result of the OFC program, 18 patients ordered do-not-resuscitate bracelets, 15 completed advanced directives, 7 submitted paperwork for disabled parking permits, 7 were referred to hospice and 4 for rehabilitation therapy. Further results are shown in the table. Conclusions: Structured outpatient palliative care family conferences improve satisfaction of end-of-life discussions and facilitate integration of palliative care options. Enhanced communication between providers, patients and loved ones eases the challenges of such discussions. The OFC approach could be a model for integrating palliative care in community cancer clinics. [Table: see text]
Abstract 2950: The European Study of Epidemiology and Treatment of Cardiac Inflammatory Diseases (ESETCID) - Intermediate Analysis of Immunosuppressive Therapy
Authors: Bernhard Maisch, Susanne Koelsch, Guenter Hufnagel, Sabine Pankuweit
Journal: Circulation (2006)

Treatment of inflammatory dilated Cardiomyopathy (iDCM) is still controversial. In ESETCID pts with autoreactive (virus-negative) myocarditis and an ejection fraction < 45% were randomised for 6 months of treatment with azathioprin (2mg/kg BW/day for 1 month and 0.85mg/kg BW/day for 5 months) + prednisolone (1.25mg/kg BW/for 1 month and 0.3mg/kg BW/day for 5 months) or placebo on top of their heart failure treatment.

Patients : 2452 pts were screened, 89 pts (mean age 47 ± 9 years, 70 male, 19 female) with iDCM could be randomized for ESETCID after informed consent.

Methods: Endomyocardial biopsies (EMB) were examined for lymphocytes & macrophages by immunhistochemistry according to the World Heart Federation (WHF)-criteria (≥ 14 infiltrating cells/mm2). Pts with viral or bacterial genomes for Parvo B19, coxsackie, influenza-, adeno-, cytomegalo-, herpes, EB virus, chlamydia and borreli the immunosuppression. 51 pts (41 m) were treated with verum, 37 pts ( 38m) with placebo.

Results : Inflammation was eradicated in 59% in the treatment group, but it also vanished spontaneously in 40% in the placebo arm. The difference was significant.(p < 0,05). NYHA-association class and Minnesota Heart Failure Score improved in treatment and placebo arm to a similar extend. Ejection fraction by echo and radionuclidventriculography improved in both arms. Independent from the immunosuppressive treatment patients with no inflammation in the follow-up biopsy (n = 45) showed a more improved NYHA-class by Class 2 + 0,73 when compared to those with persisting inflammation (n = 43) with NYHA 2,37 + 0,8 (p < 0,05). Similarily ejection fraction after 6 months was more reduced in persisting inflammation (EF = 38,3 + 14,15%) when compared to healed myocarditis (EF = 40,6 + 12,2%) (p < 0,05).

Conclusion: Immunosuppression is superior to conventional heart failure treatment in the eradication of the inflammatory infiltrate iDCM patients. Patients with no infiltrate at the end of treatment of the study had improved more than those, in whom inflammation had persisted.
My Sampler of Editors
Authors: William B. Bean
Journal: New England Journal of Medicine (1980)

Morris Fishbein was born in St. Louis in 1889 and moved, before he remembered anything, to Indianapolis, where he grew up, advancing along the socioeconomic scale as his father's business changed and expanded. His formative influences were a close-knit, religious family, a reverence for learning and scholarship, and the understanding that a book was a natural object, not a pathologic one, to be read rather than avoided. Earnest and gregarious, he was also wary because he was smaller than his contemporaries. In time, Morris Fishbein became the patriarch of his clan, and as his accomplishments and fame extended, their response . . .
Cross-platform comparison of techniques to detect BRAF mutations in circulating tumor DNA of melanoma patients.
Authors: Marc G. Denis, Anne-Chantal Knol, Audrey Vallee, Sandrine Theoleyre, Guillaume Herbreteau, Amir Khammari, Brigitte Dréno
Journal: Journal of Clinical Oncology (2016)

e21026 Background: Circulating tumor DNA is an alternative source of tumor DNA that could be used for noninvasive identification of BRAF mutations at various time-points during the course of the disease. The main objective of our work was to compare the performance of several assays to detect mutant BRAF in plasma. Methods: A total of 54 patients with stage IIIc-IV melanoma (38 BRAF V600 mutated and 16 BRAF wild type) were tested prior to any treatment. Blood samples were collected in EDTA-containing tubes. Cell-free DNA was extracted from plasma using the QIAmp Circulating Nucleic Acid (Qiagen). We evaluated 3 technologies : 2 assays based on allele-specific PCR, the Therascreen BRAF RGQ kit (Qiagen) and the ctBRAF Mutation Detection Kit (Entrogen), and a digital PCR platform, the QuantStudio 3D system (Life Technologies). Results: Using the Therascreen assay, we were able to detect a BRAF mutation in plasma of 28/38 patients, yielding a positive percent agreement (PPA) of 73.7% when compared with tumor as the reference sample. Similar results were obtained using the Entrogen assay, with a PPA of 68.4% (26/38). The 2 most common activating mutations, V600E and V600K, had a similar PPA with both Qiagen and Entrogen tests. For all patients with wild type BRAF tumors, the research was negative on plasma DNA with both techniques (negative percent agreement, NPA = 100%). The QS3D digital PCR system concluded on the presence of a BRAF mutation in only 20/34 samples (PPA = 58.8%) mostly because of an insufficient number of circulating DNA copies to reach a relevant statistic value. Conclusions: The Qiagen and the Entrogen assays are based on allele-specific amplification, a technique easy to use without a specific training, unlike dPCR which requires specific equipment and training to acquire technical and interpretation skills. The unexpectedly low PPA of dPCR was attributed to the limited amount of DNA extracted from some samples. These findings suggest that the Qiagen and Entrogen plasma tests are more adapted as a screening tool for non-invasive assessment of BRAF mutation in metastatic melanoma but could be complemented with dPCR as an absolute quantification tool for follow-up. Supported in part by a grant from Roche Pharma.
Abstract 13727: How much Reduction of Radiation Exposure is Feasible in Ablation Procedures Without Affecting the Outcome? a Single Center Study on Cryoballoon Ablation in Paroxysmal Atrial Fibrillation
Authors: Vanessa Rubesch-Kütemeyer, Stephan Molatta, M. Sajid Hossain, Frauke Koch, Jürgen Vogt, Dieter Horstkotte, Klaus-Jürgen Gutleben, Georg Nölker
Journal: Circulation (2014)

Introduction:  Cryoballoon (CB) ablation has been widely adopted as a valuable alternative technique in pulmonary vein isolation (PVI) for paroxysmal atrial fibrillation (pxAF). The population treated is relatively young and radiation protection is of major importance.   Hypothesis:  We aimed to demonstrate that radiation exposure can markedly be reduced by intracardiac echocardiography (ICE) and optimized settings of the Xray system.   Methods:  A total of 140 patients were studied. In 57 consecutive patients (31 male, 58±14 years, BMI 26.7±4.2 kg/m 2 , LA 38±6 mm, LVEF 54.9±0.7) (group 1) undergoing CB PVI for treatment of pxAF, ICE was applied for transseptal puncture, confirmation of PV occlusion, guidance of wires, mapping catheters and CB and monitoring of complications. PV angiography prior to CB inflation was skipped. Thereby, fluoroscopy was avoided whenever possible. During fluoroscopy a reduced frame rate (3/s instead of 7.5/s) was chosen, distance of patient and detector was kept minimal and collimation was applied consequently. The “Care Position” functionality (Siemens, Forchheim, Germany) was used to avoid fluoroscopy during table movements. Patients from group 1 were compared to 73 similar preceding consecutive patients (45 male, 61±12 years, BMI 26.5±3.8 kg/m 2 , LA 40±6 mm, LVEF 55±3%) (group 2).   Results:  No complications occurred. Total fluoroscopy time could be reduced from 18.7±6.2 to 12.1±5.5 s (p 2  in group 1 compared to 5134±2451 μGy*m 2  in group 2 (p   Conclusions:  Radiation exposure in CB PVI could be markedly reduced without prolonging procedure times or affecting the outcome. Moreover, ICE seems to reduce total freezing times. Twelve-month follow-up will be available and presented at the meeting.
Intestinal cell damage and systemic immune activation in individuals reporting sensitivity to wheat in the absence of coeliac disease
Authors: Melanie Uhde, Mary Ajamian, Giacomo Caio, Roberto De Giorgio, Alyssa Indart, Peter H Green, Elizabeth C Verna, Umberto Volta, Armin Alaedini
Journal: Gut (2016)

Wheat gluten and related proteins can trigger an autoimmune enteropathy, known as coeliac disease, in people with genetic susceptibility. However, some individuals experience a range of symptoms in response to wheat ingestion, without the characteristic serological or histological evidence of coeliac disease. The aetiology and mechanism of these symptoms are unknown, and no biomarkers have been identified. We aimed to determine if sensitivity to wheat in the absence of coeliac disease is associated with systemic immune activation that may be linked to an enteropathy.Study participants included individuals who reported symptoms in response to wheat intake and in whom coeliac disease and wheat allergy were ruled out, patients with coeliac disease and healthy controls. Sera were analysed for markers of intestinal cell damage and systemic immune response to microbial components.Individuals with wheat sensitivity had significantly increased serum levels of soluble CD14 and lipopolysaccharide (LPS)-binding protein, as well as antibody reactivity to bacterial LPS and flagellin. Circulating levels of fatty acid-binding protein 2 (FABP2), a marker of intestinal epithelial cell damage, were significantly elevated in the affected individuals and correlated with the immune responses to microbial products. There was a significant change towards normalisation of the levels of FABP2 and immune activation markers in a subgroup of individuals with wheat sensitivity who observed a diet excluding wheat and related cereals.These findings reveal a state of systemic immune activation in conjunction with a compromised intestinal epithelium affecting a subset of individuals who experience sensitivity to wheat in the absence of coeliac disease.
Abstract 4873: ImmTACs re-direct the immune system efficiently to eradicate cancer
Authors: Giovanna Bossi, Rupert Kenefeck, Caroline Caroline Boudousquie, Jane Harper, Joseph Dukes, Nathaniel Liddy, Samantha Paston, Tara Mahon, Peter Molloy, Malkit Sami, Emma Baston, Brian Cameron, Annelise Vuidepot, Namir Hassan, Bent K. Jakobsen
Journal: Cancer Research (2016)

Abstract Immunotherapy strategies that are able to induce T cell infiltration into tumors and activate a cytotoxic T cell response have the potential to destroy the tumor. Although T cells can mediate clearance of a tumor, thymic selection and the suppressive microenvironment limit their effectiveness. To overcome poor tumor immunogenicity, we have developed a unique platform that enables the generation of ImmTACs (Immune-mobilising monoclonal TCRs Against Cancer); these are comprised of an affinity enhanced TCR specific for a cancer antigen fused to an anti-CD3 scFv. The TCR end targets and binds MHC class I/peptide complex displayed on cancerous cells while the anti-CD3 scFv end engages polyclonal T cells to mediate a potent anti-tumor response. The most advanced ImmTAC, IMCgp100, targets the HLA-A2/gp100280-288 epitope presented by melanoma cells. IMCgp100 is currently in a Phase I/IIa clinical trial for advance malignant melanoma and is showing promising clinical efficacy in some patients. Here we report a series of in vitro experiments evaluating IMCgp100 mechanism of action. IMCgp100 is able to redirect T cells from healthy donors or from melanoma patients to destroy cancer cells and secrete a range of inflammatory cytokines and chemokines associated with T cell trafficking into tumors; some of these cytokines also induce upregulation of inhibitory pathway molecules. We show that effector memory cells in the CD8+ and CD4+ T cell compartments are very efficient in eliminating melanoma cells and in expanding upon IMCgp100 engagement. The effects of combining IMCgp100 with agents that relieve the suppression imposed by immune check-point molecules have also been investigated. Citation Format: Giovanna Bossi, Rupert Kenefeck, Caroline Caroline Boudousquie, Jane Harper, Joseph Dukes, Nathaniel Liddy, Samantha Paston, Tara Mahon, Peter Molloy, Malkit Sami, Emma Baston, Brian Cameron, Annelise Vuidepot, Namir Hassan, Bent K. Jakobsen. ImmTACs re-direct the immune system efficiently to eradicate cancer. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 4873.
Abstract 1895: Metastasis-associated protein 1 drives prostate cancer progression and metastasis through regulation of onco-epimicroRNAs
Authors: Swati Dhar, Nasir A. Butt, Avinash Kumar, Xu Zhang, Anait S. Levenson
Journal: Cancer Research (2016)

Abstract Our recent studies in prostate-specific tumor suppressor Pten gene compromised transgenic mice, revealed a strategic role for Metastasis Associated protein 1 (MTA1), a component of the chromatin remodeling NuRD complex and a key regulator of metastasis, in the progression of prostate cancer. Chromatin Immunoprecipitation Sequencing (ChIP-Seq) analyses from the mouse prostate tissues showed MTA1 occupancy of several potential oncogenic miRNA target promoters including miR-22. Retrospective investigation of microRNA microarray experiments revealed downregulation of these candidate miRNAs in LNCaP cells silenced for MTA1 expression (shMTA1). Real time PCR evaluation of shMTA1 cell lines, LNCaP, DU145 and PC3M attested the microarray findings. Using miRNA-mRNA target prediction algorithms, miRanda, miRDB and Targetscan, E-cadherin (CDH1) was identified as a potential target with high context score for miR-22. Interestingly, E-cadherin, which has a pivotal role in preventing Epithelial to Mesenchymal Transition (EMT) of tumor cells was also identified as a MTA1 target gene by ChIP-Seq analysis. Further, qRT-PCR and western blot experiments validated that MTA1 levels had an inverse correlation with E-cadherin expression in these cell lines. Transient transfection of miR-22 mimics diminished E-cadherin levels while this expression was restored by miR-22 sponge inhibitors showing that miR-22 can control E-cadherin expression. Ongoing experiments aim to address the direct targeting of E-cadherin 3′UTR by miR-22 using Dual-Glo luciferase reporter assay and the functional consequences of miR-22 promoter regulation by MTA1 utilizing chromatin and RNA immunoprecipitation assays. Our studies reveal a novel and previously unrecognized role for MTA1-mediated miR-22 regulation of E-cadherin. Citation Format: Swati Dhar, Nasir A. Butt, Avinash Kumar, Xu Zhang, Anait S. Levenson. Metastasis-associated protein 1 drives prostate cancer progression and metastasis through regulation of onco-epimicroRNAs. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 1895.
Abstract 1730: Cancer stem cells might sustain stemness by the induction of autophagy in starvation stress
Authors: Go Masuda, Masakazu Yashiro, Kishu Kitayama, Yuichiro Miki, Hiroaki Kasashima, Tamami Morisaki, Tatsunari Fukuoka, Tsuyoshi Hasegawa, Masaichi Ohira, Kosei Hirakawa
Journal: Cancer Research (2016)

Abstract Background: Cancer stem cells (CSCs), which have capacity for self-renewal and cancer cell supply, have been thought to be responsible for tumor initiation, distant metastasis, and chemoresistance. Side population (SP) cells extracted by the fluorescence-activated cell sorting technique using Hoechst 33342 are thought to be enriched for CSCs. Autophagy is an intracellular degradation system that is induced under stress, such as starvation. Although autophagy has been reported to be associated with tumor progression under various stresses, the significance of autophagy in CSCs has still remained to be unknown. The aim of this study is to clarify the role of autophagy of CSCs under starvation stress. Materials and Methods: Two gastric cancer cell lines, OCUM-2MD3 and OCUM-12 were used. Two side population (SP) cell lines, OCUM-2MD3/SP and OCUM-12/SP were sorted by flow cytometry as CSC-rich cells from the parent OCUM-2MD3 and OCUM-12 cells, respectively. The effects of starvation stress, including low glucose, low amino acid, or low serum, on the stemness of CSCs were examined. The expression level of autophagy associated proteins, LC3A and LC3B, was evaluated by RT-PCR and western blotting. The effects of autophagy on the stemness and the proliferation of CSCs were examined by SP fraction and MTT assay. Chloroquine was used as an autophagy inhibitor. Results: The percentages of SP cells were significantly higher in the OCUM-12/SP cells (10.2%) and OCUM-2MD3/SP cells (12.3%) than in their parent OCUM-12 cells (2.1%) and OCUM-2MD3 cells (1.2%). The expression level of LC3A and LC3B was high in both OCUM-2MD3/SP cells and OCUM-12/SP cells, in comparison to that in OCUM-2MD3 cells and OCUM-12 cells. Starvation stress increased the autophagy status of OCUM-2MD3/SP and OCUM-12/SP cells. Chloroquine significantly decreased the SP fraction and proliferation activity of OCUM-2MD3/SP cells and OCUM-12/SP cells. Conclusion: Autophagy acts as a survival pathway in CSCs under starvation stress. CSCs might sustain stemness by the induction of autophagy in sarvation status. The autophagy inhibitor might be a promising therapy for CSCs. Citation Format: Go Masuda, Masakazu Yashiro, Kishu Kitayama, Yuichiro Miki, Hiroaki Kasashima, Tamami Morisaki, Tatsunari Fukuoka, Tsuyoshi Hasegawa, Masaichi Ohira, Kosei Hirakawa. Cancer stem cells might sustain stemness by the induction of autophagy in starvation stress. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 1730.