tbuckley/cabot-search huggingface dataset:
Sleeping Beauty transposon mutagenesis identifies genes driving the initiation and metastasis of uterine leiomyosarcoma
Authors: Michiko Kodama, Hiroko Shimura, Jean C. Tien, Justin Y. Newberg, Takahiro Kodama, Zhubo Wei, Roberto Rangel, Kosuke Yoshihara, Airi Kuruma, Aya Nakae, Kae Hashimoto, Kenjiro Sawada, Tadashi Kimura, Nancy A. Jenkins, Neal G. Copeland
Journal: Cancer Research (2021)

Abstract Uterine leiomyosarcoma (ULMS) is a malignancy, which arises from the uterine smooth muscle. Because of its rarity, aggressive nature, and extremely poor prognosis, the molecular mechanisms driving ULMS remain elusive. To identify candidate cancer genes (CCG) driving ULMS, we conducted an in vivo Sleeping Beauty (SB) transposon mutagenesis screen in uterine myometrium–specific, PTEN knockout, KRAS mutant (PTEN KO/KRAS) mice. ULMS quickly developed in SB PTEN KO/KRAS mice, but not in PTEN KO/KRAS mice, demonstrating the critical importance of SB mutagenesis for driving ULMS in this model. Subsequent sequencing of SB insertion sites in these tumors identified 19 ULMS CCGs that were significantly enriched in known cancer genes. Among them, Zfp217 and Sfmbt2 functioned at early stages of tumor initiation and appeared to be oncogenes. Expression of ZNF217, the human homolog of ZFP217, was shown to be elevated in human ULMS compared with paired normal uterine smooth muscle, where it negatively correlated with patient prognosis. Inhibition of ZNF217 suppressed, whereas overexpression induced, proliferation, survival, migration, and stemness of human ULMS. In a second ex vivo ULMS SB metastasis screen, three CCGs were identified that may drive ULMS metastasis to the lung. One of these CCGs, Nrd1 (NRDC in humans), showed stronger expression in human metastatic tumors compared with primary ULMS and negatively associated with patient survival. NRDC knockdown impaired migration and adhesion without affecting cell proliferation, whereas overexpression had the opposite effect. Together, these results reveal novel mechanism driving ULMS tumorigenesis and metastasis and identify ZNF217 and NRDC as potential targets for ULMS therapy. Significance: An in vivo Sleeping Beauty transposon mutagenesis screen identifies candidate cancer genes that drive initiation and progression of uterine leiomyosarcoma and may serve as therapeutic targets.
Clinical Characteristics and Outcomes in ESKD Patients with COVID-19 Infection in an Urban Community Hospital in Brooklyn, New York, During the Global Pandemic
Authors: Carlos M. Zapata, Yariana E. Rodriguez, Olawale Akande, Laurie Ward, Premila Bhat
Journal: Journal of the American Society of Nephrology (2020)

Zapata, Carlos M.; Rodriguez, Yariana E.; Akande, Olawale; Ward, Laurie; Bhat, Premila Author Information
A Dual‐Nanozyme‐Catalyzed Cascade Reactor for Enhanced Photodynamic Oncotherapy against Tumor Hypoxia
Authors: Miaomiao Chen, Jitao Song, Jialong Zhu, Gaobo Hong, Jing An, Erting Feng, Xiaojun Peng, Fengling Song
Journal: Advanced Healthcare Materials (2021)

Abstract Tumor hypoxia is a typical characteristic of tumor microenvironment (TME), which seriously compromises the therapeutic effect of photodynamic therapy (PDT). The development of nanozymes with oxygen‐generation ability is a promising strategy to overcome the oxygen‐dependent of PDT but remained a great challenge. Herein, a dual‐nanozymes based cascade reactor HAMF is proposed to alleviate tumor hypoxia for enhanced PDT. The hollow mesoporous silica nanoparticles (HMSNs) are constructed as an excellent nanocarrier to load ultra‐small gold nanoparticles (Au NPs) and manganese dioxide (MnO 2 ) shell via in situ reduction method, and further coordination with an efficient photosensitizer 4‐DCF‐MPYM (4‐FM), a thermally activated delayed fluorescence (TADF) fluorescein derivative. With the response to TME, MnO 2 can catalyze endogenous H 2 O 2 into O 2 and subsequently accelerating glucose oxidation by Au NPs to produce additional H 2 O 2 , which is reversely used as the substrate for MnO 2 ‐catalyzed reaction, thereby constantly producing singlet oxygen ( 1 O 2 ) for enhanced PDT upon light irradiation. This work proposed a cascade reactor based on dual‐nanozyme to relieve tumor hypoxia for effective tumor suppression, which may enrich the application of multi‐nanozymes in biomedicine.
LeafGo: Leaf to Genome, a quick workflow to produce high-quality de novo plant genomes using long-read sequencing technology
Authors: Patrick Driguez, Salim Bougouffa, Karen Carty, Alexander Putra, Kamel Jabbari, Muppala Reddy, Richard Soppe, Ming Sin Cheung, Yoshinori Fukasawa, Luca Ermini
Journal: Genome biology (2021)

Abstract Currently, different sequencing platforms are used to generate plant genomes and no workflow has been properly developed to optimize time, cost, and assembly quality. We present LeafGo, a complete de novo plant genome workflow, that starts from tissue and produces genomes with modest laboratory and bioinformatic resources in approximately 7 days and using one long-read sequencing technology. LeafGo is optimized with ten different plant species, three of which are used to generate high-quality chromosome-level assemblies without any scaffolding technologies. Finally, we report the diploid genomes of Eucalyptus rudis and E. camaldulensis and the allotetraploid genome of Arachis hypogaea .
Additional Insights Into the Use of Preterm Formula Among Neonates—Reply
Authors: Akash Sharma, Arunambika Chinnappan, M. Jeeva Sankar
Journal: JAMA Pediatrics (2021)

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 Journals 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
Redefining β-blocker response in heart failure patients with sinus rhythm and atrial fibrillation: a machine learning cluster analysis
Authors: Andreas Karwath, Karina V Bunting, Simrat K Gill, Otilia Tica, Samantha Pendleton, Furqan Aziz, Andrey D Barsky, Saisakul Chernbumroong, Jinming Duan, Alastair R Mobley, Victor Roth Cardoso, Karin Slater, John A Williams, Emma-Jane Bruce, Xiaoxia Wang, Marcus D Flather, Andrew J S Coats, Georgios V Gkoutos, Dipak Kotecha
Journal: The Lancet (2021)

Background Mortality remains unacceptably high in patients with heart failure and reduced left ventricular ejection fraction (LVEF) despite advances in therapeutics.We hypothesised that a novel artificial intelligence approach could better assess multiple and higher-dimension interactions of comorbidities, and define clusters of β-blocker efficacy in patients with sinus rhythm and atrial fibrillation. MethodsNeural network-based variational autoencoders and hierarchical clustering were applied to pooled individual patient data from nine double-blind, randomised, placebo-controlled trials of β blockers.All-cause mortality during median 1•3 years of follow-up was assessed by intention to treat, stratified by electrocardiographic heart rhythm.The number of clusters and dimensions was determined objectively, with results validated using a leave-one-trial-out approach.This study was prospectively registered with ClinicalTrials.gov(NCT00832442) and the PROSPERO database of systematic reviews (CRD42014010012).Findings 15 659 patients with heart failure and LVEF of less than 50% were included, with median age 65 years (IQR 56-72) and LVEF 27% (IQR 21-33).3708 (24%) patients were women.In sinus rhythm (n=12 822), most clusters demonstrated a consistent overall mortality benefit from β blockers, with odds ratios (ORs) ranging from 0•54 to 0•74.One cluster in sinus rhythm of older patients with less severe symptoms showed no significant efficacy (OR 0•86, 95% CI 0•67-1•10; p=0•22).In atrial fibrillation (n=2837), four of five clusters were consistent with the overall neutral effect of β blockers versus placebo (OR 0•92, 0•77-1•10; p=0•37).One cluster of younger atrial fibrillation patients at lower mortality risk but similar LVEF to average had a statistically significant reduction in mortality with β blockers (OR 0•57, 0•35-0•93; p=0•023).The robustness and consistency of clustering was confirmed for all models (p<0•0001 vs random), and cluster membership was externally validated across the nine independent trials.Interpretation An artificial intelligence-based clustering approach was able to distinguish prognostic response from β blockers in patients with heart failure and reduced LVEF.This included patients in sinus rhythm with suboptimal efficacy, as well as a cluster of patients with atrial fibrillation where β blockers did reduce mortality.
Wireless and Flexible Skin Moisture and Temperature Sensor Sheets toward the Study of Thermoregulator Center (Adv. Healthcare Mater. 17/2021)
Authors: Yuyao Lu, Yusuke Fujita, Satoko Honda, Shin‐Hsin Yang, Yan Xuan, Kaichen Xu, Takayuki Arie, Seiji Akita, Kuniharu Takei
Journal: Advanced Healthcare Materials (2021)
Metabolomics and lipidomics in NAFLD: biomarkers and non-invasive diagnostic tests
Authors: Mojgan Masoodi, Amalia Gastaldelli, Tuulia Hyötyläinen, Enara Arretxe, Cristina Alonso, Melania Gaggini, Julia Brosnan, Quentin M. Anstee, Oscar Millet, Pablo Ortiz, Jose M. Mato, Jean-Francois Dufour, Matej Orešič
Journal: Nature Reviews Gastroenterology & Hepatology (2021)
Fluticasone furoate nasal spray (FFNS) 110 lg once-daily is effective in seasonal allergic rhinitis (SAR) caused by grass pollen
Authors: Wytske Fokkens, Rain Jõgi, I Sidorenko, Brigita Šitkauskienė, Jacqueline van Tongeren, M Faris, A Ellsworth, M Caldwell
Journal: Allergy (2007)
Letter to the Editor: The Differences Between the Reverse Transcriptional Efficiency of HBV Pregenomic RNA and Transcriptional Efficiency of HBV Covalently Closed Circular DNA
Authors: Hao Liao, Yan Liu, Jun Wang, Guanxun Cheng, Dongping Xu, Junhui Chen, Fengmin Lu
Journal: Hepatology (2021)
PRMT5 disruption drives antitumor immunity in cervical cancer by reprogramming T cell-mediated response and regulating PD-L1 expression
Authors: Yongshuai Jiang, Yuanyang Yuan, Ming Chen, Shengzhe Li, Jun Bai, Yuanteng Zhang, Ying Sun, Guojue Wang, Haiyan Xu, Ziyu Wang, Yingxia Zheng, Hong Nie
Journal: Theranostics (2021)

Rationale: Protein arginine methyltransferase 5 (PRMT5) is an oncogene that promotes tumor cell proliferation, invasion and metastasis. However, the underlying mechanisms by which PRMT5 contributes to the progression of cervical cancer and especially the tumor microenvironment remain poorly understood. Methods: PRMT5 expression level was analyzed by Q-PCR, western blot, immunohistochemistry, and TCGA database. The role of PRMT5 in tumor growth was observed by transplanted tumor models, and the function of T cells in tumor microenvironment and in vitro co-culture system was investigated through flow cytometry. The transcriptional regulation of PRMT5 was analyzed using luciferase reporter and chromatin immunoprecipitation (ChIP) assay. The therapeutic effect of PRMT5 inhibitor was evaluated in a cervical cancer cell line transplanted tumor model. Results: We observed that the mRNA and protein expression levels of PRMT5 were increased in cervical cancer tissues, and the high expression of PRMT5 was associated with poor outcomes in cervical cancer patients. The absence of PRMT5 significantly inhibited tumor growth in a cervical cancer transplanted tumor model, and importantly, PRMT5 absence in tumors led to increase the number and enhance the function of tumor infiltrating T cells. Mechanistically, PRMT5 enhanced the transcription of STAT1 through symmetric dimethylation of histone H3R2 and thus promoted PD-L1 expression in cervical cancer cells. Moreover, in an in vitro co-culture system, knockdown of PRMT5 in tumor cells could directly enhance the expression of IFN-γ, TNF-α and granzyme B in T cells. These results suggested that PRMT5 promoted the development of cervical cancer by the crosstalk between tumor cells and T cells. Furthermore, the PRMT5 inhibitor EPZ015666 treatment could suppress tumor growth in a cervical cancer transplanted tumor model. Conclusion: Our results clarify a new mechanism which PRMT5 knockdown in cervical cancer cells drives an antitumor function via reprogramming T cell-mediated response and regulating PD-L1 expression. Thus, our study highlights that PRMT5 may be a potential target for cervical cancer therapy.
Rising Use of Multitarget Stool DNA Testing for Colorectal Cancer
Authors: Richard M. Hoffman, Barcey T. Levy, James E. Allison
Journal: JAMA Network Open (2021)

Deborah A. Fisher, MD; Nicole Princic, MS; Lesley-Ann Miller-Wilson, PhD; Kathleen Wilson, MPH; A. Mark Fendrick, MD; Paul Limburg, MD
Conjugation‐Free Multilamellar Protein‐Lipid Hybrid Vesicles for Multifaceted Immune Responses
Authors: Bon Il Koo, Seon‐Mi Jin, Hayeon Kim, Dong Jae Lee, Eunji Lee, Yoon Sung Nam
Journal: Advanced Healthcare Materials (2021)

Abstract Various lipid‐based nanocarriers have been developed for the co‐delivery of protein antigens with immunological adjuvants. However, their in vivo potency in vaccine delivery is limited by structural instability, which causes off‐target delivery and low cross‐presentation efficacies. Recent works employ covalent cross‐linking to stabilize the lipid nanostructures, though the immunogenicity and side effects of chemically modified protein antigens and lipids can cause a long‐lasting safety issue. Here robust “conjugation‐free” multilamellar protein antigen‐lipid hybrid nanovesicles (MPLVs) are introduced through the antigen‐mediated self‐assembly of unilamellar lipid vesicles for the co‐delivery of protein antigens and immunologic adjuvants. The nanocarriers coated with monophosphoryl lipid A and hyaluronic acids elicit highly increase antigen‐specific immune responses in vitro and in vivo. The MPLVs increase the generation of immunological surface markers and cytokines in mouse‐derived bone‐marrow dendritic cells compared to soluble antigens with adjuvants. Besides, the vaccination of mice with the MPLVs significantly increase the production of anti‐antigen antibody and interferon‐gamma via the activation of CD4 + and CD8 + T cells, respectively. These findings suggest that MPLVs can serve as a promising nanovaccine delivery platform for efficient antigen cross‐presentation through the efficient co‐delivery of protein antigens with adjuvants.
Medicare for More — Why We Still Need a Public Option and How to Get There
Authors: Jacob S. Hacker
Journal: New England Journal of Medicine (2021)

Interview with Prof. Erin Fuse Brown on lessons from U.S. states that have enacted public option health plans (11:46)Download Public Option 2.0 may be the most realistic way to guarantee universal coverage with a broad choice of providers and with medical prices held down by the government. If the United States is to achieve this elusive goal, however, advocates need to lay the groundwork now.
Metabolic improvement after gastric bypass correlates with changes in IGF-regulatory proteins stanniocalcin-2 and IGFBP-4
Authors: Rikke Hjortebjerg, Kirstine N. Bojsen-Møller, Mette Søeby, Claus Oxvig, Sten Madsbad, Jan Frystyk
Journal: Metabolism (2021)

Pregnancy-associated plasma protein-A (PAPP-A) is an enzyme that increases IGF-activity through cleavage of IGF-binding proteins (IGFBPs), primarily IGFBP-4, whereby bound IGF-I becomes released as a free molecule. The enzymatic activity of PAPP-A is irreversibly suppressed by the glycoprotein stanniocalcin-2 (STC2). Pre-clinical and clinical studies suggest that the STC2 - PAPP-A - IGFBP-4 axis is important in controlling local IGF-action. STC2, PAPP-A and IGFBP-4 are expressed in adipose tissue, and as bariatric surgery markedly reduces the amount of fat, we found it relevant to study the impact of Roux-en-Y gastric bypass (RYGB) on circulating concentrations of this IGF-regulatory network.Analysis of fasting blood samples from 20 obese subjects, hereof 10 with preoperative type 2 diabetes, investigated before RYGB, and 1 week, 3 months and 12 months post-surgery. Members of the IGF-system were analyzed by immunoassays, bioactive IGF by cell-based IGF-I receptor activation assay. We compared changes in IGF-system components with changes in fasting plasma insulin and glucose, and HbA1c.PAPP-A remained unchanged, but STC2 decreased following RYGB (p < 0.05). The PAPP-A substrate IGFBP-4 declined (p < 0.01), whereas levels of PAPP-A specific IGFBP-4 fragments increased (p < 0.05), indicating an increased PAPP-A enzymatic activity post-RYGB. Further, the reduction in intact IGFBP-4 correlated with increased levels of bioactive IGF (p < 0.05). In multivariable regression analyses, an improved glucose metabolism correlated with reductions in STC2 and IGFBP-4, and with increases in bioactive IGF and IGF-I (p < 0.05).After 12 months, RYGB caused reduced serum concentrations of intact IGFBP-4 and STC2, whereas serum PAPP-A remained at pre-operative levels. However, concentrations of PAPP-A generated IGFBP-4 fragments increased, pointing to an overall increased PAPP-A enzymatic activity following RYGB. Notably, reductions in intact IGFBP-4 and STC2 associated with improvements in glucose metabolism. Therefore, we propose that STC2 and IGFBP-4 are involved in the metabolic improvement that follows RYGB.
Surveillance for Adverse Events After COVID-19 mRNA Vaccination
Authors: Nicola P. Klein, Ned Lewis, Kristin Goddard, Bruce Fireman, Ousseny Zerbo, Kayla E. Hanson, James G. Donahue, Elyse O. Kharbanda, Allison Naleway, Jennifer Clark Nelson, Stan Xu, W. Katherine Yih, Jason M. Glanz, Joshua T. B. Williams, Simon J. Hambidge, Bruno J. Lewin, Tom T. Shimabukuro, Frank DeStefano, Eric S. Weintraub
Journal: JAMA (2021)

Safety surveillance of vaccines against COVID-19 is critical to ensure safety, maintain trust, and inform policy.To monitor 23 serious outcomes weekly, using comprehensive health records on a diverse population.This study represents an interim analysis of safety surveillance data from Vaccine Safety Datalink. The 10 162 227 vaccine-eligible members of 8 participating US health plans were monitored with administrative data updated weekly and supplemented with medical record review for selected outcomes from December 14, 2020, through June 26, 2021.Receipt of BNT162b2 (Pfizer-BioNTech) or mRNA-1273 (Moderna) COVID-19 vaccination, with a risk interval of 21 days for individuals after vaccine dose 1 or 2 compared with an interval of 22 to 42 days for similar individuals after vaccine dose 1 or 2.Incidence of serious outcomes, including acute myocardial infarction, Bell palsy, cerebral venous sinus thrombosis, Guillain-Barré syndrome, myocarditis/pericarditis, pulmonary embolism, stroke, and thrombosis with thrombocytopenia syndrome. Incidence of events that occurred among vaccine recipients 1 to 21 days after either dose 1 or 2 of a messenger RNA (mRNA) vaccine was compared with that of vaccinated concurrent comparators who, on the same calendar day, had received their most recent dose 22 to 42 days earlier. Rate ratios (RRs) were estimated by Poisson regression, adjusted for age, sex, race and ethnicity, health plan, and calendar day. For a signal, a 1-sided P < .0048 was required to keep type I error below .05 during 2 years of weekly analyses. For 4 additional outcomes, including anaphylaxis, only descriptive analyses were conducted.A total of 11 845 128 doses of mRNA vaccines (57% BNT162b2; 6 175 813 first doses and 5 669 315 second doses) were administered to 6.2 million individuals (mean age, 49 years; 54% female individuals). The incidence of events per 1 000 000 person-years during the risk vs comparison intervals for ischemic stroke was 1612 vs 1781 (RR, 0.97; 95% CI, 0.87-1.08); for appendicitis, 1179 vs 1345 (RR, 0.82; 95% CI, 0.73-0.93); and for acute myocardial infarction, 935 vs 1030 (RR, 1.02; 95% CI, 0.89-1.18). No vaccine-outcome association met the prespecified requirement for a signal. Incidence of confirmed anaphylaxis was 4.8 (95% CI, 3.2-6.9) per million doses of BNT162b2 and 5.1 (95% CI, 3.3-7.6) per million doses of mRNA-1273.In interim analyses of surveillance of mRNA COVID-19 vaccines, incidence of selected serious outcomes was not significantly higher 1 to 21 days postvaccination compared with 22 to 42 days postvaccination. While CIs were wide for many outcomes, surveillance is ongoing.
Regulatory Network of PD1 Signaling Is Associated with Prognosis in Glioblastoma Multiforme
Authors: Camila M. Lopes-Ramos, Tatiana Belova, Tess H. Brunner, Marouen Ben Guebila, Daniel Osorio, John Quackenbush, Marieke L. Kuijjer
Journal: Cancer Research (2021)

Abstract Glioblastoma is an aggressive cancer of the brain and spine. While analysis of glioblastoma ‘omics data has somewhat improved our understanding of the disease, it has not led to direct improvement in patient survival. Cancer survival is often characterized by differences in gene expression, but the mechanisms that drive these differences are generally unknown. We therefore set out to model the regulatory mechanisms associated with glioblastoma survival. We inferred individual patient gene regulatory networks using data from two different expression platforms from The Cancer Genome Atlas. We performed comparative network analysis between patients with long- and short-term survival. Seven pathways were identified as associated with survival, all of them involved in immune signaling; differential regulation of PD1 signaling was validated to correspond with outcome in an independent dataset from the German Glioma Network. In this pathway, transcriptional repression of genes for which treatment options are available was lost in short-term survivors; this was independent of mutational burden and only weakly associated with T-cell infiltration. Collectively, these results provide a new way to stratify patients with glioblastoma that uses network features as biomarkers to predict survival. They also identify new potential therapeutic interventions, underscoring the value of analyzing gene regulatory networks in individual patients with cancer. Significance: Genome-wide network modeling of individual glioblastomas identifies dysregulation of PD1 signaling in patients with poor prognosis, indicating this approach can be used to understand how gene regulation influences cancer progression.