tbuckley/cabot-search huggingface dataset:
Abstract 12690: The Contribution of Circulating Platelets to AAA Growth and Rupture
Authors: Ayman Elbadawi, Doran S Mix, Adam J Doyle, Gbolahan O Ogunbayo, Mohamed A Omer, Albert P Owens, Scott J Cameron
Journal: Circulation (2019)

Introduction: There is paucity of data on the role of platelets in the pathophysiology of abdominal aortic aneurysm (AAA), yet most AAA are coincident with luminal thrombus. Hypothesis: Platelets a...
Abstract 9884: Cardiac Iron Concentration in Relation to Systemic Iron Status and Disease Severity in Dilated Cardiomyopathy
Authors: Valentin G Hirsch, Jörn Tonges, Julia Bode, Dominik Berliner, Julian D Widder, Felicitas Escher, Vitalii Mutsenko, Bomee Chung, Fatemeh Rostami, Anja Guba-Quint, Evangelos Giannitsis, Heinz-Peter Schultheiss, Carla Vogt, Johann B Bauersachs, Kai C Wollert, Tibor Kempf
Journal: Circulation (2019)

Aims: Low cardiac iron levels promote heart failure in experimental models. While cardiac iron concentration (CI) is decreased in patients with advanced heart failure with reduced ejection fraction...
Peter Searell Andrews
Authors: Neil Andrews
Journal: BMJ (2020)

Peter Searell Andrews was consultant pathologist at Kettering General Hospital (1958-90) and Home Office pathologist for the East Midlands. Wartime measures shortened his training at Cambridge but added the experience of being a night time dispatch motorcyclist. His postgraduate training at the Middlesex Hospital included national service as a pathologist in Benghazi, followed by a MD research thesis into rodent ulcers …
Transmission of SARS-CoV-2 Involving Residents Receiving Dialysis in a Nursing Home — Maryland, April 2020
Authors: Benjamin F. Bigelow, Olive Tang, Gregory R. Toci, Norberth Stracker, Fatima Sheikh, Kara M. Jacobs Slifka, Shannon A. Novosad, John A. Jernigan, Sujan C. Reddy, Morgan J. Katz
Journal: MMWR Morbidity and Mortality Weekly Report (2020)

SARS-CoV-2, the virus that causes coronavirus disease 2019 (COVID-19), can spread rapidly in nursing homes once it is introduced (1,2). To prevent outbreaks, more data are needed to identify sources of introduction and means of transmission within nursing homes. Nursing home residents who receive hemodialysis (dialysis) might be at higher risk for SARS-CoV-2 infections because of their frequent exposures outside the nursing home to both community dialysis patients and staff members at dialysis centers (3). Investigation of a COVID-19 outbreak in a Maryland nursing home (facility A) identified a higher prevalence of infection among residents undergoing dialysis (47%; 15 of 32) than among those not receiving dialysis (16%; 22 of 138) (p<0.001). Among residents with COVID-19, the 30-day hospitalization rate among those receiving dialysis (53%) was higher than that among residents not receiving dialysis (18%) (p = 0.03); the proportion of dialysis patients who died was 40% compared with those who did not receive dialysis (27%) (p = 0.42).Careful consideration of infection control practices throughout the dialysis process (e.g., transportation, time spent in waiting areas, spacing of machines, and cohorting), clear communication between nursing homes and dialysis centers, and coordination of testing practices between these sites are critical to preventing COVID-19 outbreaks in this medically vulnerable population.
High oligoclonality of immunoglobulins in SARS-CoV2 positive patients
Authors: Marie Kolopp-Sarda, Pierre Miossec
Journal: Annals of the Rheumatic Diseases (2020)

<h3>Introduction</h3> The Rehabilitation Training (ReTrain) intervention aims to improve functional mobility, adherence to poststroke exercise guidelines and quality of life for people after stroke. A definitive randomised controlled trial (RCT) is required to assess the clinical and cost-effectiveness of ReTrain, which is based on Action for Rehabilitation from Neurological Injury (ARNI). The purpose of this pilot study is to assess the feasibility of such a definitive trial and inform its design. <h3>Methods and analysis</h3> A 2-group, assessor-blinded, randomised controlled external pilot trial with parallel mixed-methods process evaluation and economic evaluation. 48 participants discharged from clinical rehabilitation despite residual physical disability will be individually randomised 1:1 to ReTrain (25 sessions) or control (exercise advice booklet). Outcome assessment at baseline, 6 and 9 months include Rivermead Mobility Index; Timed Up and Go Test; modified Patient-Specific Functional Scale; 7-day accelerometry; Stroke Self-efficacy Questionnaire, exercise diary, Fatigue Assessment Scale, exercise beliefs and self-efficacy questionnaires, SF-12, EQ-5D-5L, Stroke Quality of Life, Carer Burden Index and Service Receipt Inventory. Feasibility, acceptability and process outcomes include recruitment and retention rates; with measurement burden and trial experiences being explored in qualitative interviews (20 participants, 3 intervention providers). Analyses include descriptive statistics, with 95% CI where appropriate; qualitative themes; intervention fidelity from videos and session checklists; rehearsal of health economic analysis. <h3>Ethics and dissemination</h3> National Health Service (NHS) National Research Ethics Service approval granted in April 2015; recruitment started in June. Preliminary studies suggested low risk of serious adverse events; however (minor) falls, transitory muscle soreness and high levels of postexercise fatigue are expected. Outputs include pilot data to inform whether to proceed to a definitive RCT and support a funding application; finalised Trainer and Intervention Delivery manuals for multicentre replication of ReTrain; presentations at conferences, public involvement events; internationally recognised peer-reviewed journal publications, open access sources and media releases. <h3>Trial registration number</h3> NCT02429180; Pre-results.
Implications of Nonphysiological Ovarian Primordial Follicle Activation for Fertility Preservation
Authors: Johanne Grosbois, Melody Devos, Isabelle Demeestere
Journal: Endocrine Reviews (2020)

Abstract In recent years, ovarian tissue cryopreservation has rapidly developed as a successful method for preserving the fertility of girls and young women with cancer or benign conditions requiring gonadotoxic therapy, and is now becoming widely recognized as an effective alternative to oocyte and embryo freezing when not feasible. Primordial follicles are the most abundant population of follicles in the ovary, and their relatively quiescent metabolism makes them more resistant to cryoinjury. This dormant pool represents a key target for fertility preservation strategies as a resource for generating high-quality oocytes. However, development of mature, competent oocytes derived from primordial follicles is challenging, particularly in larger mammals. One of the main barriers is the substantial knowledge gap regarding the regulation of the balance between dormancy and activation of primordial follicles to initiate their growing phase. In addition, experimental and clinical factors also affect dormant follicle demise, while the mechanisms involved remain largely to be elucidated. Moreover, most of our basic knowledge of these processes comes from rodent studies and should be extrapolated to humans with caution, considering the differences between species in the reproductive field. Overcoming these obstacles is essential to improving both the quantity and the quality of mature oocytes available for further fertilization, and may have valuable biological and clinical applications, especially in fertility preservation procedures. This review provides an update on current knowledge of mammalian primordial follicle activation under both physiological and nonphysiological conditions, and discusses implications for fertility preservation and priorities for future research.
Decitabine- and 5-azacytidine resistance emerges from adaptive responses of the pyrimidine metabolism network
Authors: Xiaorong Gu, Rita Tohme, Benjamin Tomlinson, Nneha Sakre, Metis Hasipek, Lisa Durkin, Caroline Schuerger, Dale Grabowski, Asmaa M. Zidan, Tomas Radivoyevitch, Changjin Hong, Hetty Carraway, Betty Hamilton, Ronald Sobecks, Bhumika Patel, Babal K. Jha, Eric D. Hsi, Jaroslaw Maciejewski, Yogen Saunthararajah
Journal: Leukemia (2020)

Mechanisms-of-resistance to decitabine and 5-azacytidine, mainstay treatments for myeloid malignancies, require investigation and countermeasures. Both are nucleoside analog pro-drugs processed by pyrimidine metabolism into a deoxynucleotide analog that depletes the key epigenetic regulator DNA methyltranseferase 1 (DNMT1). Here, upon serial analyses of DNMT1 levels in patients' bone marrows on-therapy, we found DNMT1 was not depleted at relapse. Showing why, bone marrows at relapse exhibited shifts in expression of key pyrimidine metabolism enzymes in directions adverse to pro-drug activation. Further investigation revealed the origin of these shifts. Pyrimidine metabolism is a network that senses and regulates deoxynucleotide amounts. Deoxynucleotide amounts were disturbed by single exposures to decitabine or 5-azacytidine, via off-target depletion of thymidylate synthase and ribonucleotide reductase respectively. Compensating pyrimidine metabolism shifts peaked 72-96 h later. Continuous pro-drug exposures stabilized these adaptive metabolic responses to thereby prevent DNMT1-depletion and permit exponential leukemia out-growth as soon as day 40. The consistency of the acute metabolic responses enabled exploitation: simple treatment modifications in xenotransplant models of chemorefractory leukemia extended noncytotoxic DNMT1-depletion and leukemia control by several months. In sum, resistance to decitabine and 5-azacytidine originates from adaptive responses of the pyrimidine metabolism network; these responses can be anticipated and thus exploited.
Abstract 17080: A 3D Printed Ex Vivo Left Heart Simulator Quantifies and Validates Posterior Ventricular Anchoring Neochordoplasty
Authors: Michael J Paulsen, Jung Hwa Bae, Annabel M Imbrie-Moore, Hanjay Wang, Justin M Farry, Michael A Lin, Camille E Hironaka, Haley J Lucian, Bryan B Edwards, Akshara D Thankore, John W MacArthur, Amanda N Steele, Lyndsay Stapleton, Kiah M Williams, Daniela Deschamps, Rohun Kulkarni, Mark R Cutkosky, Y. Joseph Woo
Journal: Circulation (2018)

Introduction: The posterior ventricular anchoring neochordal (PVAN) repair is a nonresectional, single-suture technique for correcting posterior leaflet prolapse. While this technique has demonstrated clinical efficacy, a possible limitation is the stability of the suture anchored into myocardium as opposed to the fibrous portion of a papillary muscle. Hypothesis: We hypothesize that the PVAN suture serves only to position the leaflet for coaptation, after which systolic forces will be distributed throughout the valve, resulting in low peak forces on the suture. Methods: A left heart simulator was constructed using 3D printing, tuned to generate physiological pressure and flow waveforms, then validated. Porcine mitral valves (n=9) were dissected and mounted within the simulator. Chordal forces were measured using Fiber Bragg Grating (FBG) sensors, sewn in place using PTFE suture. FBG sensors are strain gauges made of 125 μ m optical fibers that use reflected peak wavelength changes to measure strain. Hemodynamic and echocardiographic data were also collected. Isolated severe mitral regurgitation (MR) was induced by cutting P2 primary chordae. The valve was repaired using the PVAN technique, anchoring the suture to a customized force-sensing post positioned to mimic in vivo placement. Results: Forces on 1° and 2° chordae of both anterior and posterior leaflets were significantly elevated in the prolapse condition ( P &lt; 0.05). PVAN resulted in elimination of MR in all valves, as well as normalization of chordae forces to baseline levels for posterior primary ( P &lt; 0.01 ) , posterior secondary ( P &lt; 0.01 ) , and anterior primary chordae ( P &lt; 0.05 ) , with reduction in anterior secondary chordal forces approaching significance ( P = 0.055 ) . Peak forces on the PVAN stitch were minimal, even compared to the forces experienced by primary chordae of normal, healthy valves ( P &lt; 0.05). Conclusions: The PVAN technique eliminates MR by effectively positioning the posterior leaflet for optimal coaptation, distributing the forces amongst the subvalvular apparatus. Given the extremely low forces involved, the strength of the ventricular anchoring suture and myocardial anchoring point should not be a limiting factor.
A Hydrogen‐Bonded Extracellular Matrix‐Mimicking Bactericidal Hydrogel with Radical Scavenging and Hemostatic Function for pH‐Responsive Wound Healing Acceleration
Authors: Zainab Ahmadian, Alexandra Correia, Masoud Hasany, Patrícia Figueiredo, Faramarz Dobakhti, Mohammad Reza Eskandari, Seyed Hojjat Hosseini, Ramin Abiri, Shiva Khorshid, Jouni Hirvonen, Hélder A. Santos, Mohammad‐Ali Shahbazi
Journal: Advanced Healthcare Materials (2020)

Abstract Generation of reactive oxygen species, delayed blood clotting, prolonged inflammation, bacterial infection, and slow cell proliferation are the main challenges of effective wound repair. Herein, a multifunctional extracellular matrix‐mimicking hydrogel is fabricated through abundant hydrogen bonding among the functional groups of gelatin and tannic acid (TA) as a green chemistry approach. The hydrogel shows adjustable physicochemical properties by altering the concentration of TA and it represents high safety features both in vitro and in vivo on fibroblasts, red blood cells, and mice organs. In addition to the merit of facile encapsulation of cell proliferation‐inducing hydrophilic drugs, accelerated healing of skin injury is obtained through pH‐dependent release of TA and its multifaceted mechanisms as an antibacterial, antioxidant, hemostatic, and anti‐inflammatory moiety. The developed gelatin‐TA (GelTA) hydrogel also shows an outstanding effect on the formation of extracellular matrix and wound closure in vivo via offered cell adhesion sites in the backbone of gelatin that provide increased re‐epithelialization and better collagen deposition. These results suggest that the multifunctional GelTA hydrogel is a promising candidate for the clinical treatment of full‐thickness wounds and further development of wound dressing materials that releases active agents in the neutral or slightly basic environment of infected nonhealing wounds.
Maternal High-Dose Vitamin D Supplementation and Offspring Bone Mineralization Until Age 6 Years
Authors: Pengxiang Zhou, Xiaomei Tong
Journal: JAMA Pediatrics (2020)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA Pediatrics HomeNew OnlineCurrent IssueFor Authors Podcast Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA Pediatrics journal
Antagonistic anti-LILRB1 monoclonal antibody regulates antitumor functions of natural killer cells
Authors: Heyu Chen, Yuanzhi Chen, Mi Deng, Samuel John, Xun Gui, Ankit Kansagra, Weina Chen, Jaehyup Kim, Cheryl Lewis, Guojin Wu, Jingjing Xie, Lingbo Zhang, Ryan Huang, Xiaoye Liu, Hisashi Arase, Yang Huang, Hai Yu, Wenxin Luo, Ningshao Xia, Ningyan Zhang, Zhiqiang An, Cheng Cheng Zhang
Journal: Journal for ImmunoTherapy of Cancer (2020)

Background Current immune checkpoint blockade strategies have been successful in treating certain types of solid cancer. However, checkpoint blockade monotherapies have not been successful against most hematological malignancies including multiple myeloma and leukemia. There is an urgent need to identify new targets for development of cancer immunotherapy. LILRB1, an immunoreceptor tyrosine-based inhibitory motif-containing receptor, is widely expressed on human immune cells, including B cells, monocytes and macrophages, dendritic cells and subsets of natural killer (NK) cells and T cells. The ligands of LILRB1, such as major histocompatibility complex (MHC) class I molecules, activate LILRB1 and transduce a suppressive signal, which inhibits the immune responses. However, it is not clear whether LILRB1 blockade can be effectively used for cancer treatment. Methods First, we measured the LILRB1 expression on NK cells from cancer patients to determine whether LILRB1 upregulated on NK cells from patients with cancer, compared with NK cells from healthy donors. Then, we developed specific antagonistic anti-LILRB1 monoclonal antibodies and studied the effects of LILRB1 blockade on the antitumor immune function of NK cells, especially in multiple myeloma models, in vitro and in vivo xenograft model using non-obese diabetic (NOD)-SCID interleukin-2Rγ-null mice. Results We demonstrate that percentage of LILRB1 + NK cells is significantly higher in patients with persistent multiple myeloma after treatment than that in healthy donors. Further, the percentage of LILRB1 + NK cells is also significantly higher in patients with late-stage prostate cancer than that in healthy donors. Significantly, we showed that LILRB1 blockade by our antagonistic LILRB1 antibody increased the tumoricidal activity of NK cells against several types of cancer cells, including multiple myeloma, leukemia, lymphoma and solid tumors, in vitro and in vivo . Conclusions Our results indicate that blocking LILRB1 signaling on immune effector cells such as NK cells may represent a novel strategy for the development of anticancer immunotherapy.
Hnf4a Is Required for the Development of Cdh6-Expressing Progenitors into Proximal Tubules in the Mouse Kidney
Authors: Sierra S. Marable, Eunah Chung, Joo-Seop Park
Journal: Journal of the American Society of Nephrology (2020)

Hepatocyte NF 4α (Hnf4a) is a major regulator of renal proximal tubule (PT) development. In humans, a mutation in HNF4A impairs PT functions and is associated with Fanconi renotubular syndrome (FRTS). In mice, mosaic deletion of Hnf4a in the developing kidney reduces the population of PT cells, leading to FRTS-like symptoms. The molecular mechanisms underlying the role of Hnf4a in PT development remain unclear.The gene deletion tool Osr2Cre removed Hnf4a in developing nephrons in mice, generating a novel model for FRTS. Immunofluorescence analysis characterized the mutant phenotype, and lineage analysis tested whether Cadherin-6 (Cdh6)-expressing cells are PT progenitors. Genome-wide mapping of Hnf4a binding sites and differential gene analysis of Hnf4a mutant kidneys identified direct target genes of Hnf4a.Deletion of Hnf4a with Osr2Cre led to the complete loss of mature PT cells, lethal to the Hnf4a mutant mice. Cdh6high, lotus tetragonolobus lectin-low (LTLlow) cells serve as PT progenitors and demonstrate higher proliferation than Cdh6low, LTLhigh differentiated PT cells. Additionally, Hnf4a is required for PT progenitors to differentiate into mature PT cells. Genomic analyses revealed that Hnf4a directly regulates the expression of genes involved in transmembrane transport and metabolism.Hnf4a promotes the differentiation of PT progenitors into mature PT cells by regulating the expression of genes associated with reabsorption, the major function of PT cells.
Interferon Regulatory Factor 4 Orchestrates the Response to B-Cell Receptor in Chronic Lymphocytic Leukemia Cells By Regulating Ikaros
Authors: Rossana Maffei, Stefania Fiorcari, Silvia Martinelli, Stefania Benatti, Patrizia Zucchini, Giulia Debbia, Leonardo Potenza, Mario Luppi, Roberto Marasca
Journal: Blood (2017)
Unsupervised Inference of Protein Fitness Landscape from Deep Mutational Scan
Authors: Jorge Fernandez-de-Cossio-Diaz, Guido Uguzzoni, Andrea Pagnani
Journal: Molecular Biology and Evolution (2020)

The recent technological advances underlying the screening of large combinatorial libraries in high-throughput mutational scans deepen our understanding of adaptive protein evolution and boost its applications in protein design. Nevertheless, the large number of possible genotypes requires suitable computational methods for data analysis, the prediction of mutational effects, and the generation of optimized sequences. We describe a computational method that, trained on sequencing samples from multiple rounds of a screening experiment, provides a model of the genotype-fitness relationship. We tested the method on five large-scale mutational scans, yielding accurate predictions of the mutational effects on fitness. The inferred fitness landscape is robust to experimental and sampling noise and exhibits high generalization power in terms of broader sequence space exploration and higher fitness variant predictions. We investigate the role of epistasis and show that the inferred model provides structural information about the 3D contacts in the molecular fold.
The Utility of Early Broncholaveolar Lavage in Prolonged Neutropenic Patients with Pulmonary Nodules
Authors: Dina Khalaf, Steven M. Chan, Vikas Gupta, Andrzej Lutynski, Dawn Maze, Mark D. Minden, Yoichiro Natori, Rhea Pavan, Amr Rostom, Anna Rydlewski, Aaron Schimmer, Andre Schuh, Hassan Sibai, Karen W.L. Yee, Shahid Husain
Journal: Blood (2017)
Second Autologous Stem Cell Transplantation in Poor Stem Cell Mobilizers Multiple Myeloma Patients
Authors: Matjaz Sever, Giulia Sbianchi, Simona Iacobelli, Steffie van der Werf, Wiktor-Jedrzejczak Wieslaw, Didier Blaise, Jane F. Apperley, Mohamad Mohty, Christof Scheid, Keith Wilson, Nigel H Russel, Peter Kalhs, Patrice Chevallier, Mark Ringhoffer, Guido Kobbe, Jiri Mayer, Edgar Jost, Teresa Zudaire, Xaver Schiel, Cecilia Isaksson, Marek Trneny, Stefan Schönland, Curly Morris, Laurent Garderet, Nicolaus Kroeger
Journal: Blood (2017)
Self‐Amplified Apoptosis Targeting Nanoplatform for Synergistic Magnetic–Thermal/Chemo Therapy In Vivo
Authors: Wei Liu, Li Chen, Ming Chen, Wu Wang, Xiaoling Li, Hong Yang, Shiping Yang, Zhiguo Zhou
Journal: Advanced Healthcare Materials (2020)

Abstract The low efficiency homing of nanomaterials in tumors remains a major challenge in nanomedicine. Inspired by the apoptosis targeting properties of phosphatidylserine (PS), a self‐amplified apoptosis targeting nanoplatform (MNPs‐ZnDPA/ β ‐Lap) is fabricated combining Zn 0.4 Co 0.6 Fe 2 O 4 @Zn 0.4 Mn 0.6 Fe 2 O 4 nanoparticles (MNPs) with an excellent magnetic hyperthermia effect, a chemotherapeutic drug of β ‐lapachone ( β ‐Lap) with the promotion of cell apoptosis, and the good apoptosis targeting moiety of Zn(II)‐bis(dipicolylamine) (bis‐ZnDPA) for PS. In an apoptotic 4T1 xenograft model, MNPs‐ZnDPA/ β ‐Lap can first accumulate in tumors by the EPR effect. The released β ‐Lap triggers the apoptosis of cancer cells in the tumor and increases the apoptotic target, which results in amplifying their apoptosis targeting properties. This self‐amplified apoptosis targeting efficiency of MNPs‐ZnDPA/ β ‐Lap almost inhibits the growth of tumors with the synergistic magnetic–thermal/chemo therapy, which can offer a significant promise for targeting cancer theranostics.