tbuckley/cabot-search huggingface dataset:
Abstract 189: HuR, RNA Stabilizing Protein, Regulation of Pluripotency and Differentiation in iPSCs
Authors: Sahana Suresh Babu, Johnson Rajasingh, Wing Tak Wong, Prasanna Krishnamurthy
Journal: Circulation Research (2017)

Background: The Hu family of RNA-binding proteins, HuR (also known as ELAVL1 or human embryonic lethal abnormal vision-like protein), binds to the 3’-untranslated region of mRNAs and regulates transcript stability and translation. Global deletion of HuR is embryonically lethal in mice and plays a critical role in progenitor cell survival and biology. Induced-pluripotent stem cells (iPSC) have distinct transcriptional machinery for the maintenance of pluripotency and achievement of differentiation. However, the exact role of HuR in pluripotency or differentiation of iPSC to cardiomyocytes (iCM) remains unclear. Methods: HuR knockdown in human dermal fibroblast-derived iPSCs was achieved by CRISPR/Cas9 or lentiviral shRNA transduction and subsequently differentiated into cardiomyocytes (iCM). Then, the expression of HuR, pluripotency and cardiomyocyte markers were evaluated on days 0, 1, 3, 6, 8 and 17 following the initiation of differentiation. Results: At basal level, HuR expression was higher in the iPSCs compared to dermal fibroblasts. Upon differentiation of iPSCs into iCM, HuR mRNA expression gradually reduced with significantly lower levels on day 17. As expected, pluripotency markers gradually reduced upon differentiation with significantly lower levels from day 6 onwards. We observed a corresponding increase in ISL1, MESP1 (mesoderm/cardiac progenitor markers) from day 3 through day 8 with a steep fall from day 8 to day 17. This was associated with Myosin light chain-2V and GATA4 expression increases from day 8 through day 17. Interestingly, knockdown of HuR resulted in clumps of colonies with differentiated cells and a corresponding increase in cardiac-troponin positive cells. However, as a general observation, HuR knockdown reduced beating intensity compared to wild type cells. Conclusions: Based on these data, we could speculate that HuR might be necessary for maintenance of pluripotency and loss of which renders cells to differentiate in culture. HuR knockdown yields higher number of c-troponin positive cells but its effect on functional maturity of iCM needs to be further evaluated.
Recent Advances in Physiology.
Journal: JAMA (1963)

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
Targeting disialoganglioside GD2 with chimeric antigen receptor-redirected T cells in lung cancer
Authors: Loïc Reppel, Ourania Tsahouridis, Jason Akulian, Ian J Davis, Hong Lee, Giovanni Fucà, Jared Weiss, Gianpietro Dotti, Chad V Pecot, Barbara Savoldo
Journal: Journal for ImmunoTherapy of Cancer (2022)

Background We explored whether the disialoganglioside GD2 (GD2) is expressed in small cell lung cancer (SCLC) and non-SCLC (NSCLC) and can be targeted by GD2-specific chimeric antigen receptor (CAR) T cells. Methods GD2 expression was evaluated in tumor cell lines and tumor biopsies by flow cytometry and immunohistochemistry. We used a GD2.CAR that coexpress the IL-15 to promote T-cell proliferation and persistence, and the inducible caspase 9 gene safety switch to ablate GD2.CAR-T cells in case of unforeseen toxicity. The antitumor activity of GD2.CAR-T cells was evaluated using in vitro cocultures and in xenograft models of orthotopic and metastatic tumors. The modulation of the GD2 expression in tumor cell lines in response to an epigenetic drug was also evaluated. Results GD2 was expressed on the cell surface of four of fifteen SCLC and NSCLC cell lines (26.7%) tested by flow cytometry, and in 39% of SCLC, 72% of lung adenocarcinoma and 56% of squamous cell carcinoma analyzed by immunohistochemistry. GD2 expression by flow cytometry was also found on the cell surface of tumor cells freshly isolated from tumor biopsies. GD2.CAR-T cells exhibited antigen-dependent cytotoxicity in vitro and in vivo in xenograft models of GD2-expressing lung tumors. Finally, to explore the applicability of this approach to antigen low expressing tumors, we showed that pretreatment of GD2 low/neg lung cancer cell lines with the Enhancer of zeste homolog 2 inhibitor tazemetostat upregulated GD2 expression at sufficient levels to trigger GD2.CAR-T cell cytotoxic activity. Conclusions GD2 is a promising target for CAR-T cell therapy in lung cancer. Tazemetostat treatment could be used to upregulate GD2 expression in tumor cells, enhancing their susceptibility to CAR-T cell targeting.
Effect of Orlistat on Weight and Body Composition in Obese Adolescents: A Randomized Controlled Trial—Correction
Authors: Ekachai Jenwitheesuk, Ram Samudrala
Journal: JAMA (2005)

drug binding affinity in terms of the inhibitory constant (K i ) was calculated every time the drug molecule was moved.After repeating this procedure for all of the drugs for each protein, the 20 drugs with the lowest K i values were considered high-affinity drug candidates.Further details of the molecular dynamics simulation and docking protocols are available elsewhere. 5Results.We predicted 20 multitarget drugs that showed high affinity across 2 or more proteins (FIGURE).Four are drugs approved by the US Food and Drug Administration for treatment of diseases other than malaria: KN62 (targeting 3 proteins), protoporphyrin IX, phthalylsulfathiazole, and sulfaphenazole (targeting 2 proteins each).The other 16 are experimental, each targeting up to 6 proteins.The best drugs in terms of multitarget functionality were STI-571 (targeting 6 proteins), bisindolylmaleimide x, GW8510, and Piper (targeting 5 proteins each).The best combination of 2 drugs was bisindolylmaleimide x and GW8510, which together target 10 Plasmodium proteins.An analysis of 3 known single-target antimalarial drugs against these proteins showed that our calculated K i s for these drugs compared well with experimentally determined values (when available) and that the inhibitory activity usually ranked within the top 5th percentile compared with our entire set of drugs (TABLE ).Conclusions.Promising vaccines targeting multiple Plasmodium proteins have been evaluated. 9,10In a similar fashion, we propose designing new antimalarial drugs that simultaneously target multiple Plasmodium proteins.Our computational drug screening protocol provides evidence for 20 approved or experimental drugs that bind strongly to 13 Plasmodium proteins.We recommend that these drug candidates be experimentally tested for inhibition of Plasmodium growth and used as a starting point for further design of a high-efficacy multitarget antimalarial drug.
IS IT THE PLAGUE?
Journal: JAMA (1900)

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
Associations of Income Volatility With Incident Cardiovascular Disease and All-Cause Mortality in a US Cohort
Authors: Tali Elfassy, Samuel L. Swift, M. Maria Glymour, Sebastian Calonico, David R. Jacobs, Elizabeth R. Mayeda, Kiarri N. Kershaw, Catarina Kiefe, Adina Zeki Al Hazzouri
Journal: Circulation (2019)

Background: Income volatility is on the rise and presents a growing public health problem. Because in many epidemiological studies income is measured at a single point in time, the association of long-term income volatility with incident cardiovascular disease (CVD) and mortality has not been adequately explored. The goal of this study was to examine associations of income volatility from 1990 to 2005 with incident CVD and all-cause mortality in the subsequent 10 years. Methods: The Coronary Artery Risk Development in Young Adults Study is an ongoing prospective cohort study conducted within urban field centers in Birmingham, AL; Chicago, IL; Minneapolis, MN; and Oakland, CA. We studied 3937 black and white participants 23 to 35 years of age in 1990 (our study baseline). Income volatility was defined as the intraindividual SD of the percent change in income across 5 assessments from 1990 to 2005. An income drop was defined as a decrease of ≥25% from the previous visit and less than the participant’s average income from 1990 to 2005. CVD events (fatal and nonfatal) and all-cause mortality between 2005 and 2015 were adjudicated with the use of medical records and death certificates. CVD included primarily acute events related to heart disease and stroke. Results: A total of 106 CVD events and 164 deaths occurred between 2005 and 2015 (incident rate, 2.76 and 3.66 per 1000 person-years, respectively). From Cox models adjusted for sociodemographic, behavioral, and CVD risk factors, higher income volatility and more income drops were associated with greater CVD risk (high versus low volatility: hazard ratio, 2.07; 95% CI, 1.10–3.90; ≥2 versus 0 income drops: hazard ratio, 2.54; 95% CI, 1.24–5.19) and all-cause mortality (high versus low volatility: hazard ratio, 1.78; 95% CI,1.03–3.09; ≥2 versus 0 income drops: hazard ratio, 1.92; 95% CI, 1.07–3.44). Conclusions: In a cohort of relatively young adults, income volatility and drops during a 15-year period of formative earning years were independently associated with a nearly 2-fold risk of CVD and all-cause mortality.
Criteria for judging the immune markers of COVID‐19 disease vaccines
Authors: Nan Lin, Haoxuan Fu, Dan Pu, Yuxin Quan, Yueyi Li, Xiaomeng Yin, Yuhao Wei, Hang Wang, Xuelei Ma, Xiawei Wei
Journal: MedComm (2021)

As severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) sweeping the world, effective and affordable vaccines are in urgent need. A reliable system for the assessment of SARS-CoV-2 vaccines would boost the development of vaccines and reduce the research cost. We constructed a logistic regression model and analyzed the relationship between antibody (Ab) level and efficacy of different vaccine types. The relationship between assessment dates and Ab levels was depicted by plotting the mean of Ab levels evolved over time and a fitted cubic polynomial model. Anti-spike immunoglobulin G (IgG) could best estimate the vaccine efficacy (VE) (adjusted R2 = 0.731) and neutralizing Ab to live SARS-CoV-2 also explained a fine relationship (adjusted R2 = 0.577). Neutralizing Abs to live SARS-CoV-2 in inactivated virus vaccines reached a peak during days 40-60, and their receptor-binding domain (RBD)-IgG peaked during days 40-50. For messenger RNA (mRNA) and viral vector vaccines, their neutralizing Ab to live SARS-CoV-2 peaked later than day 40, and for RBD-IgG during days 30-50. For mRNA and viral vector vaccines, their peak time of Abs was later than that in inactivated virus vaccines. RBD-IgG peaked earlier than Ab to live SARS-CoV-2. Anti-spike IgG and Ab to live SARS-CoV-2 may be good immune markers for VE assessment.
Lipid level alterations in the Helsinki Heart Study
Authors: Mark R. Goldstein
Journal: JAMA (1989)

<h3>To the Editor. —</h3> The Helsinki Heart Study<sup>1</sup>demonstrated a significant decrease in coronary heart disease morbidity and mortality in middle-aged dyslipidemic men treated with gemfibrozil vs a placebo. Unfortunately, overall mortality was unchanged because of an increase in violence, accidents, and intracranial hemorrhage in the treated group. Further analysis<sup>2</sup>of that study published in the Aug 5 issue of<i>JAMA</i>revealed that the reduction in coronary heart disease incidence over the placebo group was largest in the Fredrickson type IIB and smallest in the type IIA dyslipidemic men, despite the fact that the largest reductions in low-density lipoprotein cholesterol levels were in the type IIA group. Also, changes in lipoprotein levels in the gemfibrozil group were related to medication compliance—subjects were arbitrarily divided into quartiles based on average capsule counts. Data comparing overall mortality in each of the gemfibrozil-treated IIA, IIB, and IV Fredrickson types would be
Clinical Impact of Clonal and Subclonal TP53, SF3B1, BIRC3, and ATM Mutations in Chronic Lymphocytic Leukemia
Authors: Ferran Nadeu, Julio Delgado, Cristina Royo, Tycho Bauman, Tatjana Stankovic, Magda Pinyol, Pedro Jares, Alba Navarro, David Martín-García, Sílvia Beà, Itziar Salaverria, Ceri Oldreive, Marta Aymerich, Helena Suárez-Cisneros, Maria Rozman, Neus Villamor, Dolors Colomer, Armando López-Guillermo, Marcos González, Miguel Alcoceba, María José Terol, Enrique Colado, Xose S Puente, Carlos López-Otín, Anna Enjuanes, Elías Campo
Journal: Blood (2015)
Multiparametric 18F-FDG and 68GA-DOTATOC PET Imaging in Bone Metastatic Meningioma Before Radionuclide Therapy
Authors: Elise Mairal, Elodie Chevalier, Laetitia Imbert, Caroline Boursier-Joppin, Antoine Verger
Journal: Clinical Nuclear Medicine (2022)

Abstract This report presents the case of a 61-year-old woman with assessment of fronto-temporo-sphenoidal refractory meningioma before radionuclide therapy with pretherapeutic 68 Ga-DOTATOC PET/CT. Given the discovery of osteolytic lesions, 18 F-FDG PET/CT is planned to search for the primitive origin. Meningioma bone metastasis is confirmed with spine biopsies. The presence of dedifferentiated meningioma lesions indicating that high somatostatin receptor expression does not necessarily coincide with areas of increased glucose metabolism. 18 F-FDG and 68 Ga-DOTATOC PET/CT allows optimal characterization of tumor heterogeneity and guide targeted therapeutic management before PPRT.
Neuron-Restrictive Silencer Factor Limits Myocyte Gα <sub>O</sub> Expression and Is Protective in Heart Failure Progression
Authors: Samuel Sossalla, Donald M. Bers
Journal: Circulation Research (2022)

any signaling pathways have been implicated in the development and progression of cardiac hypertrophy to heart failure (HF) and arrhythmias.These include multiple GPCRs (G-protein-coupled receptors; eg, angiotensin II), kinases (PKA, PKC, CaMKII [Ca-calmodulin-dependent protein kinase]), phosphatases (eg, CaN [calcineurin]), and transcriptional modifiers (eg, NFATs, HDACs [histone deacetylases], MEF2, and GATA4) that drive structural remodeling and altered excitation-contraction coupling signaling to result in altered contraction/relaxation and electrophysiology.
Patient-reported outcomes with first-line nivolumab plus cabozantinib versus sunitinib in patients with advanced renal cell carcinoma treated in CheckMate 9ER: an open-label, randomised, phase 3 trial
Authors: David Cella, Robert J Motzer, Cristina Suarez, Steven I Blum, Flavia Ejzykowicz, Melissa Hamilton, Joel F Wallace, Burcin Simsek, Joshua Zhang, Cristina Ivanescu, Andrea B Apolo, Toni K Choueiri
Journal: The Lancet Oncology (2022)
Study: Business Booms for Unlicensed and Unproven Stem Cell Treatments
Authors: Rita Rubin
Journal: JAMA (2022)

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 Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More 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 journal
Zika-Associated Birth Defects Reported in Pregnancies with Laboratory Evidence of Confirmed or Possible Zika Virus Infection — U.S. Zika Pregnancy and Infant Registry, December 1, 2015–March 31, 2018
Authors: Nicole M. Roth, Megan R. Reynolds, Elizabeth L. Lewis, Kate R. Woodworth, Shana Godfred-Cato, Augustina Delaney, Amanda Akosa, Miguel Valencia-Prado, Maura Lash, Amanda Elmore, Peter Langlois, Salma Khuwaja, Aifili Tufa, Esther M. Ellis, Eirini Nestoridi, Caleb Lyu, Nicole D Longcore, Monika Piccardi, Leah Lind, Sharon Starr, Loletha Johnson, Shea E. Browne, Michael Gosciminski, Paz E. Velasco, Fern Johnson-Clarke, Autumn Locklear, Mary Chan, Jane Fornoff, Karrie-Ann E. Toews, Julius Tonzel, Natalie S. Marzec, Shelby Hale, Amy E. Nance, Teri Willabus, Dianna Contreras, Sowmya N. Adibhatla, Lisa Iguchi, Emily Potts, Elizabeth Schiffman, Katherine Lolley, Brandi Stricklin, Elizabeth Ludwig, Helentina Garstang, Meghan Marx, Emily Ferrell, Camille Moreno-Gorrin, Kimberly Signs, Paul Romitti, Vinita Leedom, Brennan Martin, Louisa Castrodale, Amie Cook, Carolyn Fredette, Lindsay Denson, Laura Cronquist, John F. Nahabedian, Neha Shinde, Kara Polen, Suzanne M. Gilboa, Stacey W. Martin, Janet D. Cragan, Dana Meaney-Delman, Margaret A. Honein, Van T. Tong, Cynthia A. Moore
Journal: MMWR Morbidity and Mortality Weekly Report (2022)

Zika virus infection during pregnancy can cause serious birth defects of the brain and eyes, including intracranial calcifications, cerebral or cortical atrophy, chorioretinal abnormalities, and optic nerve abnormalities (1,2). The frequency of these Zika-associated brain and eye defects, based on data from the U.S. Zika Pregnancy and Infant Registry (USZPIR), has been previously reported in aggregate (3,4). This report describes the frequency of individual Zika-associated brain and eye defects among infants from pregnancies with laboratory evidence of confirmed or possible Zika virus infection. Among 6,799 live-born infants in USZPIR born during December 1, 2015-March 31, 2018, 4.6% had any Zika-associated birth defect; in a subgroup of pregnancies with a positive nucleic acid amplification test (NAAT) for Zika virus infection, the percentage was 6.1% of live-born infants. The brain and eye defects most frequently reported included microcephaly, corpus callosum abnormalities, intracranial calcification, abnormal cortical gyral patterns, ventriculomegaly, cerebral or cortical atrophy, chorioretinal abnormalities, and optic nerve abnormalities. Among infants with any Zika-associated birth defect, one third had more than one defect reported. Certain brain and eye defects in an infant might prompt suspicion of prenatal Zika virus infection. These findings can help target surveillance efforts to the most common brain and eye defects associated with Zika virus infection during pregnancy should a Zika virus outbreak reemerge, and might provide a signal to the reemergence of Zika virus, particularly in geographic regions without ongoing comprehensive Zika virus surveillance.
Jet injectors: Perspectives for small volume delivery with lasers
Authors: Jelle Schoppink, David Fernandez Rivas
Journal: Advanced Drug Delivery Reviews (2022)

Needle-free jet injectors have been proposed as an alternative to injections with hypodermic needles. Currently, a handful of commercial needle-free jet injectors already exist. However, these injectors are designed for specific injections, typically limited to large injection volumes into the deeper layers beneath the skin. There is growing evidence of advantages when delivering small volumes into the superficial skin layers, namely the epidermis and dermis. Injections such as vaccines and insulin would benefit from delivery into these superficial layers. Furthermore, the same technology for small volume needle-free injections can serve (medical) tattooing as well as other personalized medicine treatments. The research dedicated to needle-free jet injectors actuated by laser energy has increased in the last decade. In this case, the absorption of the optical energy by the liquid results in an explosively growing bubble. This bubble displaces the rest of the liquid, resulting in a fast microfluidic jet which can penetrate the skin. This technique allows for precise control over volumes (pL to µL) and penetration depths (µm to mm). Furthermore, these injections can be tuned without changing the device, by varying parameters such as laser power, beam diameter and filling level of the liquid container. Despite the published research on the working principles and capabilities of individual laser-actuated jet injectors, a thorough overview encompassing all of them is lacking. In this perspective, we will discuss the current status of laser-based jet injectors and contrast their advantages and limitations, as well as their potential and challenges.
Dysfunction of striatal MeCP2 is associated with cognitive decline in a mouse model of Alzheimer's disease
Authors: Sangjoon Lee, Tae Kyoo Kim, Ji Eun Choi, Yunjung Choi, Minsu You, Jeewon Ryu, Yoo Lim Chun, Suji Ham, Seung Jae Hyeon, Hoon Ryu, Hye-Sun Kim, Heh-In Im
Journal: Theranostics (2022)

Cerebral Methyl-CpG binding Protein 2 (MeCP2) is involved in several psychiatric disorders that are concomitant with cognitive dysfunction. However, the regulatory function of striatal MeCP2 and its association with Alzheimer's disease (AD) has been largely neglected due to the absence of amyloid plaque accumulation in the striatal region until the later stages of AD progression. Considerable evidence indicates that neuropsychiatric symptoms related to cognitive decline are involved with striatal dysfunction. To this respect, we investigated the epigenetic function of striatal MeCP2 paralleling the pathogenesis of AD.