tbuckley/cabot-search huggingface dataset:
Functionalization of SF/HAP Scaffold with GO-PEI-miRNA inhibitor Complexes to Enhance Bone Regeneration through Activating Transcription Factor 4
Authors: Lingling Ou, Yong Lan, Zhiqiang Feng, Longbao Feng, Junjie Yang, Yu Liu, Liming Bian, Jiali Tan, Renfa Lai, Rui Guo
Journal: Theranostics (2019)

Evidence indicates that microRNAs (miRNAs) play vital roles in regulating osteogenic differentiation and bone formation. Methods: Here, we show that a polyethyleneimine (PEI)-functionalized graphene oxide (GO) complex efficiently loaded with the miR-214 inhibitor is assembled into silk fibroin/hydroxyapatite (SF/HAP) scaffolds that spatially control the release of the miR-214 inhibitor. Results: SF/HAP/GO scaffolds with nanosized GO show high mechanical strength, and their hierarchical microporous structures promote cell adhesion and growth. The SF/HAP/GO-PEI scaffolds loaded with mir-214 inhibitor (SF/HAP/GPM) were tested for their ability to enhance osteogenic differentiation by inhibiting the expression of miR-214 while inversely increasing the expression of activating transcription factor 4 (ATF4) and activating the Akt and ERK1/2 signaling pathways in mouse osteoblastic cells (MC3T3-E1) in vitro. Similarly, the scaffolds activated the osteoblastic activity of endogenous osteoblast cells to repair critical-sized bone defects in rats without the need for loading osteoblast cells. Conclusion: This technology is used to increase osteogenic differentiation and mineralized bone formation in bone defects, which helps to achieve cell-free scaffold-based miRNA-inhibitor therapy for bone tissue engineering.
Light‐Induced Redox‐Responsive Smart Drug Delivery System by Using Selenium‐Containing Polymer@MOF Shell/Core Nanocomposite
Authors: Zheng Luo, Lu Jiang, Shaoxiong Yang, Zibiao Li, Wee Mia Wilson Soh, Liyan Zheng, Xian Jun Loh, Yun‐Long Wu
Journal: Advanced Healthcare Materials (2019)

Abstract Rational design of controllable drug release systems is important for tumor treatments due to the nonspecific toxicity of many chemotherapeutics. Herein, laser or light responsive pharmaceutical delivery nanoparticles are designed, by taking the advantages of redox responsive selenium (Se) substituted polymer as shell and photosensitive porphyrin zirconium metal–organic frameworks (MOF) as core. In detail, redox cleavable di‐(1‐hydroxylundecyl) selenide (DH‐Se), biocompatible poly(ethylene glycol) (PEG), and poly(propylene glycol) (PPG) are randomly polymerized to form poly(DH‐Se/PEG/PPG urethane), which is used to coat the reactive oxygen species' (ROS) producible porous porphyrin zirconium metal organization formulation (PCN‐224 MOF) to form the final poly(DH‐Se/PEG/PPG urethane)@MOF shell–core nanoparticle with spherical shape by emulsion approach. Interestingly, poly(DH‐Se/PEG/PPG urethane)@MOF nanoparticles with loading of chemotherapeutic doxorubicin (DOX) experience a fast and controllable release, which can realize the combination of chemotherapy and photodynamic therapy upon irradiation with laser light, due to the light‐triggered ROS production by MOF which further causes the cleavage of poly(DH‐Se/PEG/PPG urethane) polymer chain and the release of encapsulated DOX. To the best of the authors' knowledge, this is the first design of utilizing MOF and selenium substituted polymer as controllable drug release carriers, which might be beneficial for precise chemotherapy and photodynamic therapy combination.
Abstract 24068: Developing a Cardiomyocyte Pipeline for Gene Edited hiPSCs
Authors: Kaytlyn Gerbin, Angelique Nelson, Brock Roberts, Joy Arakaki, Tanya Grancharova, Colette DeLizo, Ru Gunawardane
Journal: Circulation (2017)

The Allen Institute for Cell Science (AICS) is creating an open source collection of fluorescently tagged human induced pluripotent stem cell (hiPSC) lines to model cell organization and dynamics of stem cells and differentiated hiPSC-cardiomyocytes. Understanding the sub-cellular organization and the structure/function relationships of organelles within cardiomyocytes will contribute to the development of better disease models, therapies, and regenerative medicine approaches for cardiac disease. Using the WTC human iPSC line and the CRISPR/Cas9 system, we have fluorescently tagged ~20 target genes representing key cellular organelles including a few cardiac-specific genes. Edited iPSC lines are differentiated into cardiomyocytes using established protocols with either small molecules or a combination of cytokines and small molecules, which produce high-purity monolayers of beating cardiomyocytes within 1-2 weeks. Differentiation into cardiomyocytes serves as an important quality control criterion for our gene editing efforts, but also comprises an important aspect of our predictive cell modeling efforts. We plan to study the changes in localization and organization of these tagged organelles as the stem cells differentiate into cardiomyocytes using live fluorescent cell imaging. Here, we present our cardiac differentiation methods for multiple edited hiPSC lines and the quantitative and qualitative assays used to determine the efficacy of differentiation, including myofibril contraction, cardiac protein expression, and transcriptome profiling by bulk and single cell RNAseq. Additionally, we confirm the localization of cardiac proteins such as troponin T and alpha-actinin to the myofibrils in differentiated cells using image-based assays. In experiments initiated to date we have successfully differentiated multiple gene edited iPSC lines representing major cellular structures, 2 of which are specific to cardiomyocytes (ssTNNi1 and ACTN2). Some of the gene edited hiPSC lines are fluorescently-tagged for structures including focal adhesions, actin and microtubule cytoskeleton, mitochondria, nuclear envelope, desmosomes, and endoplasmic reticulum, which are all publically available to the community.
PF779 VIABILITY OF HEMATOPOETIC STEM CELLS FOLLOWING STORAGE AT −80OC WITH 5% DIMETHYLSULFOXIDE AND HEMATOLOGIC RECOVERY IN TRANSPLANTED MYELOMA PATIENTS
Authors: I. Tonev, S. Simeonov, I. Mitkov, M. Ilieva, Y. Petrov, P. Ganeva, G. Arnaudov, B. Spassov, M. Mincheff
Journal: HemaSphere (2019)

Background: Dimethylsulfoxide (DMSO) is a major intracellular cryoprotectant, used for cryopreservation of stem cells. It is toxic to both cells and patients at temperatures above 0 o C. Reduction of this effect is achieved by either washing of cells after thawing or by reduction of DMSO during freezing and storage. The latter requires addition of extracellular cryoprotectants to the freezing media. Aims: We assessed the effect of low DMSO concentration and different hematocrits of the frozen cells on cell viability and hematologic recovery in patients, transplanted for multiple myeloma. Methods: Cells were non‐programmed frozen and stored at −80 o C in a cryoprotectant solution achieving final concentrations of 5% DMSO, 3.6% of hydroxyethyl starch (HES, Weight average molecular weight 450 000 Da) and 3% of human serum albumin. The cell concentration in the frozen product for the first 77 patients (84 transplantations) varied between 100x10 6 and 250x10 6 cells/ml. In an attempt to reduce the amount of DMSO infused, for the rest of the patients (n = 172; 192 transplantations) we further decreased the volume of the freezing suspension by removal of the entire plasma. The average age of the transplanted patients was 55 (35 ‐ 71). The cells were bedside thawed at 37 o C water bath. The average cell dose was 2,95x10 6 /kg (1,3 – 9,2x10 6 /kg). Results: Viability of the stem cells following thawing assessed by trypan blue exclusion was 95,34% (70–99). The hematocrit of the frozen cells had no effect on cell viability (94,80%(low) vs 95,52%(high)). The major complaints, if any, during stem cell infusion were coughing and an increase in nausea and vomiting induced by the prior conditioning. The average time for hematological recovery was 11,66 days (between 9 and 19) for the neutrophils, and 12,17 (between 9 and 20) days for the platelets. There was no significant difference in viability and hematologic recovery (11,86 and 12,60 vs 11,59 and 12,02) between patients receiving cells frozen with low or high hematocrit. Summary/Conclusion: Dimethylsulfoxide, despite its cryoprotective properties, is toxic for stem cells at temperatures above zero C and induces many side effects (cardiac, neurologic, respiratory, etc.) in the patients. To reduce those side effects we use lower DMSO concentration, high hematocrit resulting in lower volume of the frozen cell suspension, thus reducing the final quantity of DMSO to be infused to the patients. This does not affect the cell viability or the hematologic recovery of patients after transplantation. Our easily performed method for unprogrammed freezing of stem cells with final DMSO concentration 5% at −80 o C is safe, well tolerated, and provides cryopreservation, which allows high viability and stable cell engraftment, while reducing the undesired side effects of DMSO.
Linked-read analysis identifies mutations in single-cell DNA-sequencing data
Authors: Craig L. Bohrson, Alison R. Barton, Michael A. Lodato, Rachel E. Rodin, Lovelace J. Luquette, Vinay V. Viswanadham, Doga C. Gulhan, Isidro Cortés-Ciriano, Maxwell A. Sherman, Minseok Kwon, Michael E. Coulter, Alon Galor, Christopher A. Walsh, Peter J. Park
Journal: Nature Genetics (2019)
Absolute Risk Estimates of the Association Between Concussion and Suicide
Authors: David W. Lawrence, Michael G. Hutchison
Journal: JAMA Neurology (2019)

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 Neurology 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 Neurology journal
Transition from Environmental to Partial Genetic Sex Determination in<i>Daphnia</i>through the Evolution of a Female-Determining Incipient W Chromosome
Authors: Céline M.O. Reisser, Dominique Fasel, Evelin Hürlimann, Marinela Dukič, Cathy Haag-Liautard, Virginie Thuillier, Yan Galimov, Christoph R. Haag
Journal: Molecular Biology and Evolution (2016)

Sex chromosomes can evolve during the evolution of genetic sex determination (GSD) from environmental sex determination (ESD). Despite theoretical attention, early mechanisms involved in the transition from ESD to GSD have yet to be studied in nature. No mixed ESD-GSD animal species have been reported, except for some species of Daphnia, small freshwater crustaceans in which sex is usually determined solely by the environment, but in which a dominant female sex-determining locus is present in some populations. This locus follows Mendelian single-locus inheritance, but has otherwise not been characterized genetically. We now show that the sex-determining genomic region maps to the same low-recombining peri-centromeric region of linkage group 3 (LG3) in three highly divergent populations of D. magna, and spans 3.6 Mb. Despite low levels of recombination, the associated region contains signs of historical recombination, suggesting a role for selection acting on several genes thereby maintaining linkage disequilibrium among the 36 associated SNPs. The region carries numerous genes involved in sex differentiation in other taxa, including transformer2 and sox9. Taken together, the region determining the genetic females shows characteristics of a sex-related supergene, suggesting that LG3 is potentially an incipient W chromosome despite the lack of significant additional restriction of recombination between Z and W. The occurrence of the female-determining locus in a pre-existing low recombining region illustrates one possible form of recombination suppression in sex chromosomes. D. magna is a promising model for studying the evolutionary transitions from ESD to GSD and early sex chromosome evolution.
Antibodies Predict Pegaspargase Allergic Reactions and Failure of Rechallenge
Authors: Yiwei Liu, Colton A. Smith, John C. Panetta, Wenjian Yang, Lauren E. Thompson, Jacob P. Counts, Alejandro R. Molinelli, Deqing Pei, Nancy M. Kornegay, Kristine R. Crews, Hope Swanson, Cheng Cheng, Seth E. Karol, William E. Evans, Hiroto Inaba, Ching-Hon Pui, Sima Jeha, Mary V. Relling
Journal: Journal of Clinical Oncology (2019)

Pegaspargase (PEG-ASP) has largely replaced native Escherichiacoli asparaginase (L-ASP) in the treatment of acute lymphoblastic leukemia because of its longer half-life and lower immunogenicity. Risk factors for allergic reactions to PEG-ASP remain unclear. Here, we identify risk factors for reactions in a front-line acute lymphoblastic leukemia trial and assess the usefulness of serum antibodies for diagnosing allergy and predicting rechallenge outcome.PEG-ASP was administered to 598 patients in St Jude's Total XVI study. Results were compared with Total XV study (ClinicalTrials.gov identifiers: NCT00549848 and NCT00137111), which used native L-ASP. Serum samples (n = 5,369) were analyzed for anti-PEG-ASP immunoglobulin G by enzyme-linked immunosorbent assay. Positive samples were tested for anti-polyethylene glycol (PEG) and anti-L-ASP. We analyzed potential risk factors for reactions and associations between antibodies and reactions, rechallenge outcomes, and PEG-ASP pharmacokinetics.Grade 2 to 4 reactions were less common in the Total XVI study with PEG-ASP (81 [13.5%] of 598) than in the Total XV study with L-ASP (169 [41.2%] of 410; P = 1.4 × 10-23). For Total XVI, anti-PEG, not anti-L-ASP, was the predominant component of anti-PEG-ASP antibodies (96%). In a multivariable analysis, more intrathecal therapy (IT) predicted fewer reactions (P = 2.4 × 10-5), which is consistent with an immunosuppressant contribution of IT. Anti-PEG-ASP was associated with accelerated drug clearance (P = 5.0 × 10-6). Failure of rechallenge after initial reactions was associated with anti-PEG-ASP (P = .0078) and was predicted by the occurrence of angioedema with first reaction (P = .01).Less IT therapy was the only independent clinical risk factor for reactions to PEG-ASP. PEG, and not L-ASP, is the major antigen that causes allergic reactions. Anti-PEG-ASP has utility in predicting and confirming clinical reactions to PEG-ASP as well as in identifying patients who are most likely to experience failure with rechallenge.
A Review of Perspectives on the Use of Randomization in Phase II Oncology Trials
Authors: Michael J Grayling, Munyaradzi Dimairo, Adrian P Mander, Thomas F Jaki
Journal: JNCI Journal of the National Cancer Institute (2019)

Historically, phase II oncology trials assessed a treatment's efficacy by examining its tumor response rate in a single-arm trial. Then, approximately 25 years ago, certain statistical and pharmacological considerations ignited a debate around whether randomized designs should be used instead. Here, based on an extensive literature review, we review the arguments on either side of this debate. In particular, we describe the numerous factors that relate to the reliance of single-arm trials on historical control data and detail the trial scenarios in which there was general agreement on preferential utilization of single-arm or randomized design frameworks, such as the use of single-arm designs when investigating treatments for rare cancers. We then summarize the latest figures on phase II oncology trial design, contrasting current design choices against historical recommendations on best practice. Ultimately, we find several ways in which the design of recently completed phase II trials does not appear to align with said recommendations. For example, despite advice to the contrary, only 66.2% of the assessed trials that employed progression-free survival as a primary or coprimary outcome used a randomized comparative design. In addition, we identify that just 28.2% of the considered randomized comparative trials came to a positive conclusion as opposed to 72.7% of the single-arm trials. We conclude by describing a selection of important issues influencing contemporary design, framing this discourse in light of current trends in phase II, such as the increased use of biomarkers and recent interest in novel adaptive designs.
Abstract P047: Ideal Cardiovascular Health Score and Oxidative Stress
Authors: Heval Mohamed Kelli, Chang Liu, Ayman Samman-Tahhan, Talal Alghamdi, Yi-An Ko, Fahad Choudhary, Vanessa Engineer, Muhammad Hammadah, Pratik Sandesara, Ibhar Al Mheid, Wesley O'Neal, Viola Vaccarino, Thomas Ziegler, Laurence Sperling, Michelle Lampl, Kenneth Brigham, Greg Martin, Arshed Quyyumi
Journal: Circulation (2018)

Introduction: Ideal cardiovascular health (CVH) promotion is effective for cardiovascular disease prevention. Whether increased CVH score improves oxidative stress is less clear. Our study examined the correlation between changes in ideal CVH status and oxidative stress. Hypothesis: Improvement in CVH score is correlated with changes in oxidative stress. Methods: A total of 569 actively working adult employees (51±11 years, 64% women, 21% Black) underwent a health partner-mediated lifestyle intervention. Serial counseling was delivered by a trained HP focused on promoting clinical self-knowledge and adoption of a healthier lifestyle, based on the subject’s personal schedule. Anthropometric, dietary and laboratory measurements were obtained at baseline and 1- and 2-year follow-up visits. Plasma levels of reduced (glutathione) and oxidized (cystine) aminothiols were measured by high performance liquid chromatography at baseline and follow-up to assess oxidative stress. Ratios of oxidized to reduced aminothiols (cystine/glutathione) were calculated. Linear mixed-effects model was used to examine the correlation between the changes in CVH score and changes in oxidative stress metrics overall 2 years follow-up. Results: Over 2-years, cystine (p=0.01) improved while cystine/glutathione (p=0.03) and glutathione (p&lt;0.001) decreased in the entire cohort. At baseline, CVH score was significantly associated with improvement in cystine by -0.39 μM (95% CI, -0.45, -0.32), glutathione by 0.22 μM (95% CI, 0.14, 0.29) and cystine/glutathione by -0.40 (95% CI, -0.46, -0.33). Overall, one unit increase in the CVH score was associated with a decrease of -0.33 μM (95% CI, -0.42, -0.24) in cystine and -0.38 (95% CI, -0.46, -0.29) in the cystine/glutathione ratio over 2 years. Similarly, an improvement in CVH score by one unit at 2 years was associated with improvement in glutathione by 0.30 μM (95% CI, 0.21, 0.39). Furthermore, reduction in BMI, systolic blood pressure and fasting glucose level was significantly associated with improvement in cystine (all p&lt;0.01), glutathione (all p&lt;0.01) and cystine/glutathione (all p&lt;0.01) over 2 years. Conclusion: Improvement in CVH with a lifestyle intervention was associated with early and sustained improvement in oxidative stress. Whether the impact of changes in CVH metrics on oxidative stress improves long-term morbidity and mortality needs further investigation in a controlled design.
A novel anti-CD19 chimeric T cell therapy platform ET019002 was safe and effective in inducing CR in blast crisis of CML: A case study.
Authors: Pengcheng He, Hong Liu, Haibo Liu, Qijing Li, Mina Luo, Hui Feng, Kai Ye, Bijan Nejadnik, Bingyin Shi, Cheng Liu
Journal: Journal of Clinical Oncology (2019)

e18540 Background: CML can progress to blast crisis in which the disease behaves like an acute leukemia. A novel chimeric T-cell therapy ET019002 is built upon Eureka Therapeutics ARTEMIS platform and co-expressed with an additional anti-CD19 scFv fused to the CD28 protein. ET019002 demonstrated superior preclinical anti-tumor activities to the classical anti-CD19 CAR-T cells. Herein we describe the first-in-human clinical study of ET019002 in a blast crisis of CML subject with T315I mutation, breast, skin, nasal sinus, liver, CNS involvement and heavily previous lines of therapy. Methods: The subject received infusions of ET019002 T cells at the dose of 1x10 6 receptor + T cells/kg on Day 0, 66 and 122. The primary objective is safety and the secondary objectives include ET019002 T-cell engraftment and anti-tumor efficacy. Results: The subject developed a transient fever and chills with a maximum temperature of 40.2°C 4 days post the 1 st infusion. Fever was resolved within 3 days after giving NSAIDs. No inflammatory cytokines except IL-6 were elevated during the study. IL-6 elevated 4 days post the 1 st infusion, reached peak level at 507.18 pg/ml on Day 6 and decreased to 37 pg/ml on Day 8. This was not seen after the 2 nd and the 3 rd infusion. Lumps from breast and skin disappeared and the enlarged liver and spleen were back to normal size. Bone marrow biopsy at day 12 showed lymphoblast cells were significantly decreased from baseline of 38% to the level of 1%. The leukemic cells in cerebrospinal fluid were cleared on Day 14. The copy number of tumor-related fusion gene BCR-ABL/ABL was reduced from 1.489 x 10 0 to 3.942 x 10 -5 . However, 2 months post the 1 st infusion, BCR-ABL/ABL rebounded to 3.795 x 10 -4 . The 2 nd infusion showed no effect on the relapse of the leukemia in molecular level. The 3 rd infusion resulted in CR which relapsed 1 month post the infusion. Flow cytometry analysis showed the loss of CD19 on the leukemic cells. Conclusions: Repeated infusion of autologous ET019002 was safe and achieved a three-month CR after the ET019002 T cells therapy, which could provide a window for the patient to receive curative therapies such as bridging allogeneic hematopoietic stem cells. Clinical trial information: NCT03642496.
The effect of entry and retention in opioid agonist treatment on contact with the criminal justice system among opioid-dependent people: a retrospective cohort study
Authors: Natasa Gisev, Chrianna Bharat, Sarah Larney, Timothy Dobbins, Don Weatherburn, Matthew Hickman, Michael Farrell, Louisa Degenhardt
Journal: The Lancet Public Health (2019)

Evidence on the effectiveness of opioid agonist treatment (OAT) in reducing crime is mixed. We aimed to assess the effect of OAT on crime in terms of delaying time to first charge and reducing overall charge rates, as well as the relationship between OAT retention and overall charge rates.