tbuckley/cabot-search huggingface dataset:
PGS Scaffolds Promote the In Vivo Survival and Directional Differentiation of Bone Marrow Mesenchymal Stem Cells Restoring the Morphology and Function of Wounded Rat Uterus
Authors: Bang Xiao, Wenjun Yang, Dong Lei, Jinfeng Huang, Yupeng Yin, Yiqing Zhu, Zhengwei You, Fang Wang, Shuhan Sun
Journal: Advanced Healthcare Materials (2019)

Abstract Intrauterine adhesion (IUA) causing infertility and recurrent miscarriage of reproductive female mammals usually results from endometrium injury. Nevertheless, there is no efficient therapeutic method to avoid IUA. Bone marrow derived mesenchymal stem cells (BMSCs) are an important cell source for tissue regeneration. This study designs and explores the ability of BMSC‐loaded elastic poly(glycerol sebacate) (PGS) scaffold to prevent IUA and compares the effect of PGS with poly(lactic‐co‐glycolic acid) (PLGA) and collagen scaffolds in resumption of damaged rat uteruses. The 3D architecture provided by PGS scaffolds favors the attachment and growth of rat BMSCs. In vivo bioluminescence imaging shows that compared with direct BMSC intrauterine injection, PLGA, and collagen scaffolds, the PGS scaffold significantly prolongs the retention time of BMSCs in a wounded rat uterus model. More importantly, BMSCs can directly differentiate into endometrial stromal cells after transplantation of PGS/BMSCs constructs, but not PLGA/BMSCs and collagen/BMSCs. It is found that the level of transforming growth factor β1 (TGF‐β1), basic fibroblast growth factor (bFGF), vascular endothelial growth factor, and insulin‐like growth factors in the injured endometrium adjacent to PGS/BMSCs constructs is higher than those of rats receiving PLGA/BMSCs, collagen/BMSCs, or BMSCs intrauterine transplantation. Besides, transplantation of PGS/BMSCs leads to better morphology recovery of the damaged uterus than PLGA/BMSCs and collagen/BMSCs. The receptive fertility of PGS/BMSCs is 72.2 ± 6.4%, similar to the one of collagen/BMSCs, but significantly higher than 42.3 ± 3.9% in PLGA/BMSCs. Taken together, PGS/BMSCs may be a promising candidate for preventing IUA.
Promoter orientation of the immunomodulatory<i>Bacteroides fragilis</i>capsular polysaccharide A (PSA) is off in individuals with inflammatory bowel disease (IBD)
Authors: Lucy E. Blandford, Emma L. Johnston, Jeremy D. Sanderson, William G. Wade, Alistair J. Lax
Journal: Gut Microbes (2019)

Bacteroides fragilis is a member of the normal microbiota of the lower gastrointestinal tract, but some strains produce the putative tumourigenic B. fragilis toxin (BFT). In addition, B. fragilis can produce multiple capsular polysaccharides that comprise a microcapsule layer, including an immunomodulatory, zwitterionic, polysaccharide A (PSA) capable of stimulating anti-inflammatory interleukin-10 (IL-10) production.It is known that the PSA promoter can undergo inversion, thereby regulating the expression of PSA. A PCR digestion technique was used to investigate B. fragilis capsular PSA promoter orientation using human samples for the first time. It was found that approximately half of the B. fragilis population in a healthy patient population had PSA orientated in the 'ON' position. However, individuals with inflammatory bowel disease (IBD) had a significantly lower percentage of the B. fragilis population with PSA orientated 'ON' in comparison with the other patient cohorts studied. Similarly, the putative tumourigenic bft-positive B. fragilis populations were significantly associated with a lower proportion of the PSA promoter orientated 'ON'.These results suggest that the proportion of the B. fragilis population with the PSA promoter 'ON' may be an indicator of gastrointestinal health.
Abstract 16746: Serum Paraoxonase Activity is a Better Predictor of Mortality than Serum HDL Cholesterol Level in Patients on Maintenance Hemodialysis
Authors: Yasunori Suematsu, Christina Park, Wanghui Jing, Melissa Soohoo, Elani Streja, Connie Rhee, Moti L Kashyap, Nosratola D Vaziri, Kamyar Kalantar-Zadeh, Hamid Moradi
Journal: Circulation (2017)

Introduction: End stage renal disease (ESRD) is associated with a significantly higher risk of mortality. Serum high density lipoprotein cholesterol (HDL-C) level is not an accurate predictor of mortality in ESRD as elevated levels can be paradoxically associated with worse outcomes. Markers of HDL function including antioxidant activity may be more accurate predictors of death in this ESRD population. Paraoxonase (PON), a major antioxidant enzyme associated with serum HDL, is thought to play a major role in HDL antioxidant activity. Methods: Serum PON activity was measured in 299 maintenance hemodialysis (MHD) patients who enrolled in a prospective cohort study between 06/2014-10/2014 and followed for 629.1 patient-years and 21 healthy age- and gender-matched controls. Multilevel Cox models were used to assess the association between all-cause mortality and serum PON activity, adjusting for case-mix, diabetes and dialysis vintage covariates, and rank scores were created. Results: Serum PON activity was s...
Bone Marrow-Based and Longitudinal Blood-Based MRD Tracking in Newly Diagnosed Multiple Myeloma Patients Treated with Daratumumab, Carfilzomib, Lenalidomide and Dexamethasone (DKRd): A Correlative and Clinical Phase II Study
Authors: Ola Landgren, Katie Thoren, Malin Hultcrantz, Alexander M. Lesokhin, Nikoletta Lendvai, Sham Mailankody, Eric L. Smith, Hani Hassoun, Sydney X. Lu, Donna Mastey, Meghan Salcedo, Victoria Diab, Allison Sams, Dennis Verducci, Katie Jones, Angela Harrison, Even H Rustad, Venkata Yellapantula, Theresia Akhlaghi, Heather J. Landau, Michael Scordo, David J. Chung, Gunjan L. Shah, Oscar B Lahoud, Maria E Arcila, Caleb Ho, Mikhail Roshal, Ahmet Dogan, Sergio Giralt, Neha Korde
Journal: Blood (2018)
Distribution of insulin growth factor-1 (IGF-1) binding proteins in hepatocellular carcinoma with and without cirrhosis.
Authors: Ahmed Abdelhakeem, Ahmed Omar Kaseb, Rikita Hatia, Reham Abdel-Wahab, Hesham M. Amin, Manal Hassan
Journal: Journal of Clinical Oncology (2019)

193 Background: Circulating insulin-like growth factor-1 (IGF-1) significantly declines in patients (pts) with cirrhosis and hepatocellular carcinoma (HCC), reflecting damaged hepatocytes. The bioavailability of IGF-1 is controlled by insulin-like growth factor binding proteins (IGFBPs), which bind IGF-1. IGFBPs transcription is cell specific, and are secreted mainly by the liver. Variations in circulating IGFBPs in HCC pts, especially those with non-cirrhotic HCC, has not been elucidated. We investigated the expression of these proteins in HCC with and without cirrhosis. Methods: Under Institutional Review Board approval, we measured plasma levels of seven IGFBPs in 489 cirrhotic HCC pts, 274 non-cirrhotic HCC pts, 75 pts with cirrhosis without HCC, and 200 healthy controls. Also, we assessed variations in IGFBPs plasma level between early and advanced stage HCC in the presence and absence of cirrhosis. Levels of circulating biomarkers were summarized by descriptive statistics, and both Chi-square and ANOVA tests were used to compare levels between groups. Results: IGFBPs levels varied significantly between groups (Table). Moreover, IGFBP-3 was lower in HCC pts than in healthy controls ( P ≤ 0.001), and IGFBP-1, -2, -4, and -7 were higher in HCC without cirrhosis than in healthy controls ( P = 0.001 for all). Additionally, in non-cirrhotic HCC pts, a similar pattern was observed in advanced Stage HCC compared with early stage HCC. Conclusions: Levels of circulating IGFBPs may be associated with risk of non-cirrhotic HCC and could be used as markers for underlying liver damage. [Table: see text]
Sensitization and Respiratory symptoms induced by Peach tree pollen in highly exposed Children and Adolescents.
Authors: Maria Luisa Somoza, Laura Victorio Puche, Natalia Blanca-Lopez, Elisa Haroun Diaz, Maria Garrido Arandia, J Damian López Sánchez, Araceli Diaz Perales, Gabriela Canto, Miguel Blanca
Journal: Journal of Allergy and Clinical Immunology (2019)
Chromothripsis and Chromoplexy Are Associated with DNA Instability and Adverse Clinical Outcome in Multiple Myeloma
Authors: Cody Ashby, Michael A Bauer, Yan Wang, Christopher P. Wardell, Ruslana G. Tytarenko, Purvi Patel, Erin Flynt, Maria Ortiz, Andrew Dervan, Jake Gockley, Aneta Mikulasova, Carolina D. Schinke, Sharmilan Thanendrarajan, Maurizio Zangari, Frits van Rhee, Faith E. Davies, Jonathan J Keats, Daniel Auclair, Anjan Thakurta, Brian A Walker, Gareth Morgan
Journal: Blood (2018)
Liver fat independently associates with impaired cardiac and autonomic function
Authors: David Houghton, Pawel Zalewski, Kate Hallsworth, Sophie Cassidy, Christian Thoma, Leah Avery, Joanna Slomko, Timothy Hardy, Alastair Burt, Dina Tiniakos, Kieron Hollingsworth, Roy Taylor, Christopher Day, Steven Masson, Stuart McPherson, Quentin Anstee, Julia Newton, Michael Trenell
Journal: Journal of Hepatology (2019)
miR-183-5p Inhibits Occurrence and Progression of Acute Myeloid Leukemia via Targeting Erbin
Authors: Zhuojun Zheng, Xiao Zheng, Yuandong Zhu, Xiaoyan Gu, Weiying Gu, Xiaobao Xie, Wenwei Hu, Jingting Jiang
Journal: Molecular Therapy (2019)

Erbin has been shown to have significant effects on the development of solid tumors. However, little is known about its function and regulatory mechanism in hematological malignancies. The biological function of Erbin on cell proliferation was measured in vitro and in vivo. The predicted target of Erbin was validated by dual-luciferase reporter assay and rescue experiment. We found that overexpression of Erbin could inhibit the cell proliferation and promote the cell differentiation of acute myeloid leukemia (AML) cells, whereas depletion of Erbin could enhance the cell proliferation and block the cell differentiation in AML cells in vitro and in vivo. Besides, miR-183-5p was identified as the upstream regulator that negatively regulated the Erbin expression. The results were confirmed by dual-luciferase reporter and RNA pull-down assay. Furthermore, we found that miR-183-5p negatively regulated Erbin, resulting in enhanced cell proliferation of AML cells via activation of RAS/RAF/MEK/ERK and PI3K/AKT/FoxO3a pathways. The activation of RAS/RAF/MEK/ERK and PI3K/AKT/FoxO3a pathways was mediated by Erbin interacting with Grb2. These results were also validated by rescue experiments in vitro and in vivo. All above-mentioned findings indicated that the miR-183-5p/Erbin signaling pathway might represent a novel prognostic biomarker or therapeutic target for treatment of AML. Erbin has been shown to have significant effects on the development of solid tumors. However, little is known about its function and regulatory mechanism in hematological malignancies. The biological function of Erbin on cell proliferation was measured in vitro and in vivo. The predicted target of Erbin was validated by dual-luciferase reporter assay and rescue experiment. We found that overexpression of Erbin could inhibit the cell proliferation and promote the cell differentiation of acute myeloid leukemia (AML) cells, whereas depletion of Erbin could enhance the cell proliferation and block the cell differentiation in AML cells in vitro and in vivo. Besides, miR-183-5p was identified as the upstream regulator that negatively regulated the Erbin expression. The results were confirmed by dual-luciferase reporter and RNA pull-down assay. Furthermore, we found that miR-183-5p negatively regulated Erbin, resulting in enhanced cell proliferation of AML cells via activation of RAS/RAF/MEK/ERK and PI3K/AKT/FoxO3a pathways. The activation of RAS/RAF/MEK/ERK and PI3K/AKT/FoxO3a pathways was mediated by Erbin interacting with Grb2. These results were also validated by rescue experiments in vitro and in vivo. All above-mentioned findings indicated that the miR-183-5p/Erbin signaling pathway might represent a novel prognostic biomarker or therapeutic target for treatment of AML.
IgE reactivity to Pacific cod (Gadus macrocephalus) fish allergens in dogs with canine atopic dermatitis
Authors: Ichiro Imanishi, Jumpei Uchiyama, Takako Matsuda, Keijiro Mizukami, Hidekatsu Shimakura, Tadahiro Nasukawa, Junichi Kamiie, Keigo Kurata, Masato Fujimura, Kuniyoshi Shimakura, Koji Nishifuji, Masahiro Sakaguchi
Journal: Journal of Allergy and Clinical Immunology (2019)
Abstract 18320: Layperson CPR and Defibrillation are Associated With Lower Antidepressant Use in Out-of-Hospital Cardiac Arrest Survivors
Authors: Kristian Kragholm, Kristian Bundgaard Ringgren, Rikke Nørmark Mortensen, Steen Møller Hansen, Kathrine Bach Søndergaard, Lena Karlsson, Mads Wissenberg, Fredrik Folke, Freddy Lippert, Gunnar Gislason, Lars Køber, Christian Torp-Pedersen
Journal: Circulation (2017)

Introduction: Layperson resuscitative efforts are associated with increased survival after out-of-hospital cardiac arrest (OHCA). We examined the association between layperson resuscitative efforts and antidepressant use as a marker of psychological and neurological disabilities among OHCA survivors. Methods: We included all eligible 30-day OHCA survivors from the Danish Cardiac Arrest Registry during 2001-2014. Survivors who redeemed antidepressant prescriptions within a six-month period prior to OHCA, had emergency medical service (EMS)-witnessed arrests, had OHCA of presumed non-cardiac etiology, and who were <18 years of age were excluded. We reported cumulative incidence of redeemed antidepressants and all-cause mortality within one year after OHCA according to 1) no layperson resuscitation, 2) layperson cardiopulmonary resuscitation (CPR/chest compressions) and 3) layperson defibrillation (with or without layperson chest compressions). We used multivariable adjusted cause-specific Cox regression to ...
The world is complex, not just noisy
Authors: Romain Brette
Journal: Behavioral and Brain Sciences (2018)

Abstract To deny that human perception is optimal is not to claim that it is suboptimal. Rahnev &amp; Denison (R&amp;D) point out that optimality is often ill defined. The fundamental issue is framing perception as a statistical inference problem. Outside of the lab, the real perceptual challenge is to determine the lawful structure of the world, not variables of a predetermined statistical model.
Hepatocellular carcinoma and liver metastasis treated by hafnium oxide nanoparticles activated by SBRT: A phase I/II trial.
Authors: Enrique Chajon, Marc Pracht, Thierry De Baere, France Nguyen, Jean-Pierre Bronowicki, Veronique Vendrely, Anne-Sophie Baumann, Laurent Valérie, Emmanuel Rio, Yan Rolland, Samuel Le Sourd, Pierre Gustin, Christophe Perret, Francoise Mornex, Didier Peiffert, Philippe Merle, Eric Deutsch
Journal: Journal of Clinical Oncology (2019)

340 Background: Hafnium oxide nanoparticles, NBXTR3, were developed to increase the tumor-localized high energy deposit once activated by ionizing radiation such as stereotactic body radiotherapy (SBRT) and thus to increase tumor cell death compared to the same dose of radiation. NBTXR3 is characterized by a single intratumor/intralesional (IL) administration and fits into standard RT schedule with no change in patient’s flow, treatment protocol or equipment. Herein the preliminary results of a phase I/II clinical trial evaluating this combination in patients (pts) with hepatocellular carcinoma (HCC) or liver metastasis (mets). Methods: HCC and liver mets patients were treated with an IL injection of NBTXR3 followed by SBRT (15 Gy∗3 fractions). The phase I part of the trial follows a 3+3 dose escalation design at dose levels of NBTXR3 corresponding to 10%, 15%, 22%, 33% of the baseline tumor volume. This study aims primarily to identify the Recommended Dose and the incidence of early Dose Limiting Toxicities (DLTs) of NBTXR3 activated by SBRT. Secondary endpoints include assessment of global safety profile, liver function evaluated by Child-Pugh score (CPS), AST to Platelet Ratio Index (APRI), and response rate (mRECIST/RECIST 1.1). Results: Enrollment is at the last dose level, 33%, and completed at 10% (6 pts), 15% (4 pts) and 22% (4 pts). So far, no early DLTs nor severe adverse events related to NBTXR3 were observed. Both CPS and APRI did not reveal important variations in accordance to NBTXR3 low toxicity. The best observed target lesions responses, among 7 evaluable HCC pts for response (mRECIST), were: 3 complete responses, 3 partial responses (PR) and 1 stable disease (SD) and among 5 evaluable liver mets pts: 1 PR, 3 SD and 1 progressive disease (RECIST 1.1). Conclusions: NBTXR3 is well tolerated at the 22% dose level with an overall positive safety profile. This innovative approach might constitute a valuable solution for pts with liver tumors beyond standard treatment lines. NBTXR3 was successful in a phase II/III in soft tissue sarcoma [NCT02379845] and is currently evaluated in head and neck [NCT01946867; NCT02901483], prostate [NCT02805894] and rectum cancers. Clinical trial information: NCT02721056.
Differential risk factors for slowly and rapidly-growing nontuberculous mycobacteria: A retrospective cross-sectional study
Authors: A. Santos-Silva, F. Pereira, R. Gaio, R. Duarte
Journal: Pulmonology (2019)

Nontuberculous mycobacteria (NTM) are usually classified based on the time to colony formation in subculture: rapidlygrowing mycobacteria (RGM) (<7 days), and slowly-growing mycobacteria (SGM) (≥7 days). 1,2linical patterns of disease may vary ---lung infection in patients with structural disease is mostly caused by SGM, although RGM may display a similar clinical and radiological presentation.The pattern of disseminated disease is also somewhat different: RGM usually spread from a contaminated source with direct inoculation, most commonly manifesting as skin and soft tissue infection.Conversely, SGM typically affect severely immunocompromised patients, mostly affecting deep lymph nodes, liver and spleen.Our main goal was to identify relevant features associated with an increased risk of either RGM or SGM infection.
OC-006 Halo 360 express radio-frequency ablation in the treatment of barrett’s oesophagus – the first 100 cases treated in the united kingdom
Authors: C Magee, C Gordon, J Dunn, I Penman, R Willert, H Smart, J Fernandez-Sorto, MDi Pietro, N Ravi, A Morris, P Dunne, S Subramaniam, K Kandiah, P Bhandari, L Lovat, R Haidry
Journal: Gut (2017)

Introduction  Radio-frequency ablation (RFA) for the treatment of Barrett’s oesophagus (BE) related neoplasia has become the preferred ablative intervention after endoscopic resection (ER) over the past decade. For circumferential BE, the 3 cm HALO 360 balloon can be used to treat large areas. A new device, HALO 360 Express self-sizing catheter was recently launched and can potentially allow quicker ablation times and better coverage of the mucosa due to the improved tissue/catheter contact and 4 cm balloon length.  Method  Specialist centres in the UK and Ireland submitted cases where Halo 360 express had been used.  Patients returned for follow up at 3 months after index RFA express treatment. They were analysed for surface area regression of BE and stricture formation. For those patients who went on to complete RFA treatment histological regression of intestinal metaplasia (EoT (End of Treatment) CR-IM) and dysplasia (EoT CR-D) were analysed.  Results  11 centres across the UK and Ireland submitted 116 patients treated with the Halo 360 Express Catheter. The mean age was 66 years+/-9.8. 83% were male. 38 patients had low grade dysplasia as baseline histology (32.7%); 59 patients had high grade dysplasia (50.8%) and 19 patients had intra-mucosal carcinoma (16.5%). The mean pre-treatment circumferential length of BE (C) was 5.5 cm +/-4.3 cm and the mean maximal length (M) was 7.7 cm +/-3.6 cm. 47% had had previous ER.  80/116 had at least 3 month follow up. In these, the mean% reduction in C was 77.4%+/-36.8% and the mean% reduction in M was 53.2%+/-38.2%.  11/80 (14%) patients developed strictures that required dilation at 3 months. 2/11 had been treated with 12J dose and 2/11 had had previous ER. The median number of dilations required was 2 (IQR 1–3).  19 patients had reached end of treatment biopsies. 16/19 (84%) had achieved CR-D and 16/19 (84%) had achieved CR-IM.  Conclusion  Early experience from the UK and Ireland suggest that the new RFA express is effective in reducing the SA of visible BE by 50% after the index treatment. However, the stricture rate appears high. Although the EoT numbers are small disease eradication in patients with BE neoplasia is good following index RFA express application.  Disclosure of Interest  None Declared
Abstract 20722: The Insulin-Like Growth Factor Binding Protein 5 (IGFBP5) - A Potential Biomarker for Heart Failure Transition
Authors: Monique Wölfer, Sara Khadjeh, Lavanya M Iyer, Malte Tiburcy, Gerd Hasenfuss, Wolfram-Hubertus Zimmermann, Laura C Zelarayan
Journal: Circulation (2017)

Introduction: Available pharmacological treatments for cardiovascular diseases (CVD) delay, but do not prevent the onset of heart failure (HF). To succeed with novel interventions preventing HF, it...
Structure-Based Vaccine Antigen Design
Authors: Barney S. Graham, Morgan S.A. Gilman, Jason S. McLellan
Journal: Annual Review of Medicine (2019)

Enabled by new approaches for rapid identification and selection of human monoclonal antibodies, atomic-level structural information for viral surface proteins, and capacity for precision engineering of protein immunogens and self-assembling nanoparticles, a new era of antigen design and display options has evolved. While HIV-1 vaccine development has been a driving force behind these technologies and concepts, clinical proof-of-concept for structure-based vaccine design may first be achieved for respiratory syncytial virus (RSV), where conformation-dependent access to neutralization-sensitive epitopes on the fusion glycoprotein determines the capacity to induce potent neutralizing activity. Success with RSV has motivated structure-based stabilization of other class I viral fusion proteins for use as immunogens and demonstrated the importance of structural information for developing vaccines against other viral pathogens, particularly difficult targets that have resisted prior vaccine development efforts. Solving viral surface protein structures also supports rapid vaccine antigen design and application of platform manufacturing approaches for emerging pathogens.