tbuckley/cabot-search huggingface dataset:
Non-viral Gene Therapy for Stargardt Disease with ECO/pRHO-ABCA4 Self-Assembled Nanoparticles
Authors: Da Sun, Rebecca M. Schur, Avery E. Sears, Song-Qi Gao, Amita Vaidya, Wenyu Sun, Akiko Maeda, Timothy Kern, Krzysztof Palczewski, Zheng-Rong Lu
Journal: Molecular Therapy (2019)

Stargardt disease (STGD) is an autosomal recessive retinal disorder caused by a monogenic ABCA4 mutation. Currently, there is no effective therapy to cure Stargardt disease. The replacement of mutated ABCA4 with a functional gene remains an attractive strategy. In this study, we have developed a non-viral gene therapy using nanoparticles self-assembled by a multifunctional pH-sensitive amino lipid ECO and a therapeutic ABCA4 plasmid. The nanoparticles mediated efficient intracellular gene transduction in wild-type (WT) and Abca4−/− mice. Specific ABCA4 expression in the outer segment of photoreceptors was achieved by incorporating a rhodopsin promoter into the plasmids. The ECO/pRHO-ABCA4 nanoparticles induced substantial and specific ABCA4 expression for at least 8 months, 35% reduction in A2E accumulation on average, and a delayed Stargardt disease progression for at least 6 months in Abca4−/− mice. ECO/plasmid nanoparticles constitute a promising non-viral gene therapy platform for Stargardt disease and other visual dystrophies. Stargardt disease (STGD) is an autosomal recessive retinal disorder caused by a monogenic ABCA4 mutation. Currently, there is no effective therapy to cure Stargardt disease. The replacement of mutated ABCA4 with a functional gene remains an attractive strategy. In this study, we have developed a non-viral gene therapy using nanoparticles self-assembled by a multifunctional pH-sensitive amino lipid ECO and a therapeutic ABCA4 plasmid. The nanoparticles mediated efficient intracellular gene transduction in wild-type (WT) and Abca4−/− mice. Specific ABCA4 expression in the outer segment of photoreceptors was achieved by incorporating a rhodopsin promoter into the plasmids. The ECO/pRHO-ABCA4 nanoparticles induced substantial and specific ABCA4 expression for at least 8 months, 35% reduction in A2E accumulation on average, and a delayed Stargardt disease progression for at least 6 months in Abca4−/− mice. ECO/plasmid nanoparticles constitute a promising non-viral gene therapy platform for Stargardt disease and other visual dystrophies.
New Opportunities With School-Based Telehealth
Authors: Sean M. Frey, Andrea Milne Wenderlich, Jill S. Halterman
Journal: JAMA Pediatrics (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 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
Functional flow cytometry of monocytes for routine diagnosis of innate primary immunodeficiencies
Authors: Sandra Ammann, Sebastian Fuchs, Lydia Martin-Martin, Carla N. Castro, Benedikt Spielberger, Christian Klemann, Roland Elling, Maximilian Heeg, Carsten Speckmann, Ina Hainmann, Petra Kaiser-Labusch, Gerd Horneff, Julian Thalhammer, Robbert G. Bredius, Udo zur Stadt, Kai Lehmberg, Ilka Fuchs, Caroline von Spee-Mayer, Philipp Henneke, Stephan Ehl
Journal: Journal of Allergy and Clinical Immunology (2019)
Is the End Close for the Graft-Versus-Host Disease That Is a Big Problem Following Allogeneic Hematopoetic Stem Cell Transplantation?
Authors: Osman Ilhan, Guldane Cengiz Seval, Zubeyde Nur Ozkurt, Ali Ugur Ural, Meltem Ayli, Omur Gokmen Sevindik, Sinem Civriz Bozdag, Meltem Kurt Yuksel, Zafer Gulbas, Muhit Özcan
Journal: Blood (2018)
Phase II Study of Dasatinib (SPRYCEL™) in Philadelphia Chromosome-Negative Acute and Chronic Myeloid Diseases, Including Systemic Mastocytosis.
Authors: Srdan Verstovsek, Tefferi Ayalew, Cortes Jorge, Susan O’Brien, Guillermo Garcia-Manero, Animesh Pardanani, Cem Akin, Stefan Faderl, Deborah Thomas, Hagop Kantarjian
Journal: Blood (2007)
A phase II study of intratumoral administration of the autologous immature dendritic cell (DC) vaccine used after lesion photodynamic therapy (PhDT) and immunomodulation with cyclophosphamide (Cy) in pretreated patients with disseminated malignant melanoma.
Authors: Alexey Viktorovich Novik, Irina Alexandrovma Baldueva, Mark Lvovich Gelfond, Svetlana Protsenko, Tatyana Leonidovna Nehaeva, Andrei Ivanovich Waal, Eugene Vladimirovich Vorobeychikov, Anna Borisovna Danilova, Alexey Olegovich Danilov, Anna Igorevna Semenova, Gulfiya Midhatovna Teletaeva, Vladimir Moiseyenko
Journal: Journal of Clinical Oncology (2013)

3088 Background: Immature DC can be loaded in vivo with tumor-specific antigens after tissue destruction and induce specific immune response even in pretreated patients with unfavorable prognosis. We assess clinical efficacy of this approach in melanoma patients after at least 1 line of drug therapy in metastatic setting. Methods: Totally, 14 pts were enrolled: 11 men, 3 women. Stage M1a in 4 (28%) pts, M1b in 1 (7%) and M1c was in 9 (64%) pts. Patient received Cy 300 mg IM at D0, photoditasine (PH) at D3, PhDT therapy on injectable lesion 2 hrs after PH (662 nm, 300 J). The immature DC derived from peripheral blood stem-cells were injected in irradiated lesion 6 hrs after photodynamic therapy at D3 and daily until D7 of the 21-day cycle. Vaccine dose was 60-100*10^6 cells. Toxicity was measured by CTC AE v4, efficacy by RECIST 1.0. Primary endpoint was clinical benefit rate (CBR), secondary – overall survival (OS), response rate (RR), time to progression (TTP) and toxicity. Results: 14 pts were evaluable for toxicity, 13 for response. 37 cycles of therapy were performed. 2 patients achieved PR lasting 393 and 218+ days. 5 patients were stable for 33+, 108, 113, 168 and 239 days. RR was 15 (95% CI 2-39)%, CBR – 54 (95% CI 27-81)%. Median OS was 334 days, TTP – 113 days. RR was well correlated with OS (p=0,014). No SAE or AE of 4 th degree occurred. The only grade 3 toxicity was fever. All grade 1-2 AEs were immune-related: fever (the most frequent AE), pain in the lesions, flu-like reactions, myalgia as well as high serum ALT, AST and bilirubin in patients with liver metastases. Conclusions: Thus, using the described approach for immunotherapy of melanoma has clinical efficacy and worth further developing.
Carboxyamidotriazole combined with IDO1-Kyn-AhR pathway inhibitors profoundly enhances cancer immunotherapy
Authors: Jing Shi, Chen Chen, Rui Ju, Qingzhu Wang, Juan Li, Lei Guo, Caiying Ye, Dechang Zhang
Journal: Journal for ImmunoTherapy of Cancer (2019)

<h3>Background</h3> Cancer immunotherapy has generated significant excitement, mainly as a result of the development of immune checkpoint inhibitors. The blockade of PD-1 or its ligand with antibodies has resulted in impressive clinical efficacy. However, a subset of patients does not respond to biologic therapeutics, and another subset suffers from severe immune-related adverse events in certain cases. The modulation of the immune system with small molecules might yield surprising benefits. <h3>Methods</h3> CD8<sup>+</sup> cells were obtained through a magnetic cell sorting system (MACS), and their capabilities for IFN-γ release and PD-1 expression were analyzed. The in vitro effects of drugs were studied in a coculture system of tumor cells and activated CD8<sup>+</sup> cells. We further isolated the primary tumor cells in tumor-bearing mice treated with CAI, DMF, 1-MT or a combination (CAI and DMF/CAI and 1-MT) and analyzed the percentages of CD8<sup>+</sup> T cells and PD-1<sup>+</sup>CD8<sup>+</sup> T cells among TILs. The selective anti-tumor immune reactions of the two drug combinations were confirmed in a coculture system consisting of B16-OVA cells and OVA-specific CTLs derived from OT-1 transgenic mice. The anti-tumor effects of the single drugs or combined therapies were assessed according to their capability to slow tumor growth and extend the life span of tumor-bearing mice, and they were compared with the effects of PD-1 antibody. <h3>Results</h3> CAI increased IFN-γ release from activated T cells, which might strengthen the anti-proliferative and anti-metastatic effects on cancer cells. However, CAI also stimulated IDO1-Kyn metabolic circuitry in the tumor microenvironment and facilitated tumor cell immune evasion. Combining CAI with 1-MT or DMF disrupted PD-1 expression and promoted IFN-γ production in CD8<sup>+</sup> T cells, and it also increased T lymphocyte infiltration in the tumor microenvironment, inhibited tumor growth and prolonged the life spans of tumor-bearing mice. <h3>Conclusion</h3> Inhibitors of the IDO1-Kyn-AhR pathway could abolish the negative effects of CAI on CD8<sup>+</sup> T cells and result in complementary and beneficial anti-tumor immune effects. The combination of CAI with 1-MT or DMF greatly augmented the ability of CD8<sup>+</sup> T cells to kill malignant cells and showed a strong anti-cancer capability that was superior to that of either of the single agents was is comparable with that of anti-PD-1 antibody. The combinations of small molecules utilized in this study may serve as valuable new immunotherapy strategies for cancer treatment.
Real-time toxicity prediction of Aconitum stewing system using extractive electrospray ionization mass spectrometry
Authors: Zi-Dong Qiu, Jin-Long Chen, Wen Zeng, Ying Ma, Tong Chen, Jin-Fu Tang, Chang-Jiang-Sheng Lai, Lu-Qi Huang
Journal: Acta Pharmaceutica Sinica B (2019)

Due to numerous obstacles such as complex matrices, real-time monitoring of complex reaction systems (e.g., medicinal herb stewing system) has always been a challenge though great values for safe and rational use of drugs. Herein, facilitated by the potential ability on the tolerance of complex matrices of extractive electrospray ionization mass spectrometry, a device was established to realize continuous sampling and real-time quantitative analysis of herb stewing system for the first time. A complete analytical strategy, including data acquisition, data mining, and data evaluation was proposed and implemented with overcoming the usual difficulties in real-time mass spectrometry quantification. The complex Fuzi (the lateral root of Aconitum)-meat stewing systems were real-timely monitored in 150 min by qualitative and quantitative analysis of the nine key alkaloids accurately. The results showed that the strategy worked perfectly and the toxicity of the systems were evaluated and predicated accordingly. Stewing with trotters effectively accelerated the detoxification of Fuzi soup and reduced the overall toxicity to 68%, which was recommended to be used practically for treating rheumatic arthritis and enhancing immunity. The established strategy was versatile, simple, and accurate, which would have a wide application prospect in real-time analysis and evaluation of various complex reaction systems.
Abstract 18822: Insurance Trends Among Low-Income Non-Elderly Adults in the United States by Cardiovascular Disease Status: MEPS 2007-2014
Authors: Javier Valero-Elizondo, Haider J Warraich, Joseph A Salami, Victor Okunrintemi, Rohan Khera, Jonathan C Hong, Emir Veledar, Ron Blankstein, Khurram Nasir
Journal: Circulation (2017)

Introduction: The Affordable Care Act (ACA) was enacted to expand healthcare access for uninsured & low income/poor, particularly from the expansion of Medicaid. We sought to describe the trends in...
Abstract 14345: Cardioprotective Effect of Trait Forgiveness on Elevated Heart Rates in Patients With Schizophrenia
Authors: Brian Villa, Ross W May, Frank D Fincham, Marcos A Sanchez-Gonzalez
Journal: Circulation (2015)

Background: Schizophrenia (SCH), which reduces the average life expectancy by 10-25 years, is associated with an increased risk of diabetes and cardiovascular disease. Elevated resting HR has been associated with increased risk for the development of cardiometabolic disease, which is common in SCH patients. This association may be due in part to increased sympathovagal tone inducing elevated resting HR. However, the impact of cardioprotective positive emotions such as trait forgiveness (TF) on HR and cardiac autonomic modulation via HRV in patients with SCH is not well known. We hypothesized that TF would be a significant predictor of HR in SCH patients. Methods: A total of 250 subjects (SCH patients = 80; male = 68; healthy controls [CON] = 170; Male = 115) participated in this study. SCH patients stopped antipsychotic medications 24-hrs before the experiments and were body weight (M ± SEM) (82 ± 5 Kg), aged matched (42 ± 4 years) with CON. Standardized scales were used to measure affectivity including depression (CESD), positivity of relationships (PR), rumination, and TF. After a 10-min rest period, 5-min ECG tracings were collected for HRV analysis. The non-parametric Mann-Whitney U Tests were used to evaluate the differences in HRV parameters at rest between SCH and CON. Hierarchical multiple regression (HMR) analyses were conducted to test the association between HR and affectivity to demonstrate the incremental contribution of sets of predictors in accounting for HR variance. Results: There were significant (p&lt;0.01) differences between the groups (CON vs. SCH) in HR (72 ± 1.0 vs. 87 ± 1.4) and HRV the parameters Total Power (1822 ± 134 vs. 1183 ± 148), RMSSD (32.0 ± 1.7 vs. 19.0 ± 1.6), LF (762.7 ± 80.1 vs. 337.4 ± 45.0; surrogate of baroreflex function), and PR (26.1 ± 0.4 vs. 23.5 ± 0.7), but not TF. The HMR models showed that among affective symptoms, TF had an inverse relationship with heart rates and was the only significant predictor (p&lt;.05) in the full model accounting for 8.1% in HR variance in the SCH group. Conclusions: These findings suggest that TF positively influences cardiac autonomic modulation in patients with SCH. Prospective studies aimed at examining TF as a cardioprotective behavioral intervention in SCH patients at increased cardiovascular risk.
Conditional survival probability of patients with pancreatic cancer.
Authors: Mahvish Muzaffar
Journal: Journal of Clinical Oncology (2012)

e14693 Background: Conditional survival gives more accurate estimate of survival probability for patients who have survived one or more years since initial diagnosis. The aim of this study was to analyze conditional survival probability for pancreatic cancer patients and impact of gender, age and extent of disease on conditional survival. Methods: Using the Surveillance, Epidemiology, and End Results database we analyzed 57,409 patients with pancreatic cancer diagnosed between 1990 and 2008. SEER*Stat: Version7.0.5 software was used to calculate conditional survival, defined as the calculated probability of survival having already survived a specified number of years from diagnosis, with sub-stratification by age(less than 65 yrs and above/equal 65yrs ), gender and stage summary (localized, regional and distant). Results: Conditional survival probability for patients with pancreatic cancer increased from 8.3% to 47.1% having survived one year after diagnosis. Conditional survival per gender increased from 8.5% to 49.8% in women and for men from 8.1% to 44.3%. Conditional survival probability per summary stage increased most for patients with localized disease (from 25.5% to 70.2%) as opposed to distant disease (3.2% to 37.0%). Age may have a slight impact on conditional survival probability, with increase from 12.5% to 50.7% in patient younger than 65 years, as opposed to from 5.7% to 42.3% in age group more than or equal to 65yrs. Conclusions: The expected 5-year conditional survival increases for pancreatic cancer patients who survive a number of years post diagnosis. The increase in conditional survival probability may be to a lesser extent than other cancers, but provides more useful longer term prognostic information.
Agonist Selectivity and Ion Permeation in the alpha 3 beta 4 Ganglionic Nicotinic Receptor
Authors: Anant Gharpure, Jinfeng Teng, Yuxuan Zhuang, Colleen M. Noviello, Richard M. Walsh, Rico Cabuco, Rebecca J. Howard, Nurulain T. Zaveri, Erik Lindahl, Ryan E. Hibbs
Journal: Neuron (2019)
Initial Salvage Approaches for Relapsed/Refractory Mantle Cell Lymphoma Have Comparable Response Rates, Progression-Free and Overall Survival
Authors: Sarah Caulfield, Danielle Schlafer, Jeffrey M. Switchenko, Irl Brian Greenwell, Ashley D. Staton, Kristie A. Blum, Natalie Grover, Steven I Park, Alexey Danilov, Narendranath Epperla, Timothy S. Fenske, Mehdi Hamadani, Max J Gordon, Stephanie Mathews, Kelly Valla, Christopher Flowers, Jonathon B Cohen
Journal: Blood (2017)
Negative impact of polycystic ovary syndrome on bone health: a systematic review and meta-analysis
Authors: Júlia Mottecy Piovezan, Melissa Orlandin Premaor, Fábio Vasconcellos Comim
Journal: Human Reproduction Update (2019)

Polycystic ovary syndrome (PCOS) has reproductive and metabolic aspects that may affect bone health. Controversial results from different studies regarding the risk of fractures, bone mineral density (BMD) or bone markers led to uncertainty whether PCOS might improve or deteriorate bone health.This study aimed to investigate the impact of PCOS on bone markers, BMD and fracture risk.A systematic review and a meta-analysis were carried out. PubMed, EMBASE and Cochrane databases were searched for eligible studies from 1st of January of 1990 to 9th of October of 2018. Eligible studies enrolled women older than 18 years with PCOS, which should be diagnosed according to the Rotterdam Consensus, the Androgen Excess Society, the National Institutes of Health Consensus or the International Classification of Diseases. The studies were grouped according to patient mean BMI: <27 kg/m2 or ≥27 kg/m2. The results were polled as mean difference (MD), standardized MD (SMD) and hazard ratio (HR).Overall, 921 studies were retrieved, and 31 duplicated studies were removed. After screening the titles and abstracts, 80 studies were eligible for full text reading. Of those, 23 studies remained for qualitative synthesis. With the exception of one study, all studies were considered high quality based on the Newcastle-Ottawa scale (NOS; score ≥6). Meta-analysis was performed in 21 studies, with a total of 31 383 women with PCOS and 102 797 controls. Women with PCOS with BMI <27 kg/m2 had lower BMD of the total femur (MD, -0.04; 95% CI, -0.07 to 0.00; I2 = 31%; P = 0.22) and spine (MD, -0.07; 95% CI, -0.13 to -0.01; I2 = 70%; P < 0.01) when compared with the control group, whereas for women with BMI ≥27 kg/m2 no difference was observed (femur: MD, 0.02; 95% CI, -0.02 to 0.05; I2 = 20%, P = 0.29; spine: MD, 0.02; 95% CI, -0.06 to 0.05; I2 = 0%; P = 0.84). Osteocalcin was remarkably reduced in women with PCOS with BMI <27 kg/m2 (SMD, -2.68; 95% CI, -4.70 to -0.67; I2 = 98%; P < 0.01), but in women with BMI ≥27 kg/m2, there were no differences between PCOS and controls. Few studies (n = 3) addressed the incidence of bone fractures in women with PCOS. The HR for total bone fractures did not identify differences between women with PCOS and controls.On the basis of the available evidence, it is possible to assume that PCOS in women with BMI <27 kg/m2 is associated with reduced BMD in the spine and femur, and decreased bone formation, as manifested by lower levels of circulating osteocalcin. These findings suggest that bone parameters in PCOS may be linked, to some extent, to adiposity. These studies included premenopausal women, who have already achieved peak bone mass. Hence, further prospective studies are necessary to clarify the existence of increased risk of fractures in women with PCOS.
Open-Label Early-Access Programs (EAPs) for Ibrutinib in Patients with Relapsed/ Refractory Chronic Lymphocytic Leukemia (CLL) or Mantle-Cell Lymphoma (MCL)
Authors: Carlos Sérgio Chiattone, Nelson Hamerschlak, Laura Fogliatto, Phillip Scheinberg, Ricardo Bigni, Celso Rodrigues, Bernardo Garicochea, Alex Pimenta, Tiago Oliveira Boechat, Juliane Musacchio, Jaisson Bortolini, Iara Zapparoli Goncalves, Garles Miller Matias Vieira, Valeria Buccheri, Telma Santos, Mariana Grings, Lori Parisi, Paula Barreyro
Journal: Blood (2018)
Outcome of Primary Mediastinal B Cell Lymphoma: Comparative Analysis of 123 Patients Treated with Different Strategies
Authors: Hian Li Esther Chan, Liang Piu Koh, Tiffany Tang, Soon Thye Lim, Miriam Tao, Mohamad Farid, Colin Phipps Diong, Yuh Shan Lee, Xin Liu, Koh Lay Poh, Suk Teng Chin, Yee Mei Lee, Yen-Lin Chee, Anand Jeyasekharan, Sanjay De Mel, Joanne Shu Xian Lee, Shi Wang, Gwyneth Soon, Christopher Mcnamara, LM Poon
Journal: Blood (2017)
Canadian Association of Gastroenterology Clinical Practice Guideline on the Management of Bile Acid Diarrhea
Authors: Daniel C. Sadowski, Michael Camilleri, William D. Chey, Grigorios I. Leontiadis, John K. Marshall, Eldon A. Shaffer, Frances Tse, Julian R.F. Walters
Journal: Clinical Gastroenterology and Hepatology (2019)
Increased FDG Uptake in the Center of the Gallbladder Stone
Authors: Xia Ji, Aisheng Dong
Journal: Clinical Nuclear Medicine (2019)

Abstract We present a case with a large gallbladder stone showing central hypermetabolism detected incidentally by an FDG PET/CT scan. However, the same gallbladder stone did not showed any FDG activity on the FDG PET/CT scan performed 2 years ago. The mechanism of variable FDG uptake in the same gallbladder stone is unclear, which needs further investigation.
Dictionary of Medical Science.
Journal: JAMA (1893)

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 HomeNew OnlineCurrent IssueFor Authors 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) Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More 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 journal