tbuckley/cabot-search huggingface dataset:
Abstract 466: Consideration of an Optimal Educational Strategy for High-Quality Cardiopulmonary Resuscitation and Chest Compression Fraction in Basic Life Support Simulation Training
Authors: Hiroshi Sekiguchi, Kanako Saito, Masataka Fukami, Takayuki Taira, Gen Ouchi, Yuichiro Tamaki, Tatsuma Fukuda, Kazuhiko Hanashiro, Kazuhiko Hanashiro, Kawazuma Yoshikazu, koji Yonemoto, Shigeyoshi Nakajima, Taizo Terada, Ichiro Kukita
Journal: Circulation (2019)

Introduction: The American Heart Association (AHA) is pursuing higher-quality simulation training with the goal of “Optimizing educational strategies for healthcare providers” as one of the Science Gaps in the 2015 Cardiac Arrest Guidelines. The latest guidelines suggest that increasing CCF as much as possible during CPR increases the chance of ROSC. However, in simulation training, it is important to evaluate the percentage of CCF and maintain high-quality CPR. We evaluated CPR for 10 minutes in a “High-Performance Teams Activity” of an AHA-BLS course using the HQCPR quotient and CCF indexes. Methods: We measured the rhythm chest compressions (CCs), duration of two breaths, and chest rise two times using a bag valve mask, interruption and alternation time of CC, CC resumption time after AED (shock or no shock), and CCF, which was calculated from CPR recorded for 10 minutes using the video camera. This data was evaluated using the criteria of high-quality CPR based on AHA-BLS guidelines comprising 7 items, such as “100-120 frequency per min for CC,” and the HQCPR quotient was determined. The HQCPR quotient and CCF of each team were analyzed using logistic analysis. Moreover, the BLS techniques of each teams, such as the rhythm CCs were compared with the CCF of each teams, respectively. This study was approved by the Ethics Committee of Ryukyu University and the Japan ACLS Association. Results and Conclusions: Overall, 48 teams comprising 215 subjects participated in the study. The HQCPR achievement rate for the 48 teams was 65.9%. There was no correlation between the HQCPR quotient and CCF (R2 = 0.0003). In simulation training, the CCF height did not necessarily guarantee high-quality CPR (Figure 1). In particular, as CCF increased, the duration of two breaths decreased (R2 = 0.46). An adverse effect of breaths for a very short time was noted. We propose that it is essential to evaluate CCF with HQCPR quotient to achieve “Optimizing educational strategies for healthcare providers.”
Ionizable lipid-assisted efficient hepatic delivery of gene editing elements for oncotherapy
Authors: Chunhui Li, Tongren Yang, Yuhua Weng, Mengjie Zhang, Deyao Zhao, Shuai Guo, Bo Hu, Wanxuan Shao, Xiaoxia Wang, Abid Hussain, Xing-Jie Liang, Yuanyu Huang
Journal: Bioactive Materials (2021)

CRISPR/Cas9-based gene editing has emerged as a powerful biotechnological tool, that relies on Cas9 protein and single guided RNA (sgRNA) to edit target DNA. However, the lack of safe and efficient delivery carrier is one of the crucial factors restricting its clinical transformation. Here, we report an ionizable lipid nanoparticle (iLP181, pKa = 6.43) based on iLY1809 lipid enabling robust gene editing in vitro and in vivo. The iLP181 effectively encapsulate psgPLK1, the best-performing plasmid expressing for both Cas9 protein and sgRNA targeting Polo-like kinase 1 (PLK1). The iLP181/psgPLK1 nanoformulation showed uniformity in size, regular nanostructure and nearly neutral zeta potential at pH 7.4. The nanoformulation effectively triggered editing of PLK1 gene with more than 30% efficiency in HepG2-Luc cells. iLP181/psgPLK1 significantly accumulated in the tumor for more than 5 days after a single intravenous injection. In addition, it also achieved excellent tumor growth suppression compared to other nucleic acid modalities such as siRNA, without inducing adverse effects to the main organs including the liver and kidneys. This study not only provides a clinically-applicable lipid nanocarrier for delivering CRISPR/Cas system (even other bioactive molecules), but also constitutes a potential cancer treatment regimen base on DNA editing of oncogenes.
Correction: Corrigendum: Persisting positron emission tomography lesion activity and Mycobacterium tuberculosis mRNA after tuberculosis cure
Authors: Stephanus T Malherbe, Shubhada Shenai, Katharina Ronacher, Andre G Loxton, Gregory Dolganov, Magdalena Kriel, Tran Van, Ray Y Chen, James Warwick, Laura E Via, Taeksun Song, Myungsun Lee, Gary Schoolnik, Gerard Tromp, David Alland, Clifton E Barry, Jill Winter, Gerhard Walzl
Journal: Nature Medicine (2017)
Pediatrics. The Hygienic and Medical Treatment of Children.
Journal: JAMA (1907)

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
Epigenetic silencing of SFRP1 in hepatocellular carcinoma
Authors: Ya-Wen Lin, Yu-Lueng Shih, Ming-Der Yan, Chung-Bao Hsieh, Tsai-Yuan Hsieh
Journal: Cancer Research (2007)

1147  Oncogenic activation of the Wnt/β-catenin signaling pathway is common in hepatocellular carcinoma (HCC). The secreted frizzled-related proteins (SFRPs) function as negative regulators of Wnt signaling and have important implications in carcinogenesis. Frequent promoter hypermethylation of SFRPs has been identified in human cancer. However, the role of SFRPs in hepatocellular carcinoma (HCC) is not clear. Recently, we have shown that SFRP1 is frequently downregulated through promoter hypermethylation by methylation specific polymerase chain reaction (MS-PCR) and bisulfite sequencing. To investigate the role of SFRP1 in hepatoma cells, we uses reexpression of SFRP1 in these β-catenin-dependent hepatoma cell lines (Huh6 and HepG2). Restoration of SFRP1 could attenuate Wnt signaling in the Huh6 hepatoma cells with β-catenin point mutation, decrease abnormal accumulation of free β-catenin in the nucleus, and then suppresses cell growth. Conversely, restoration of SFRP1 in HepG2 hepatoma cells with truncated β-catenin could not block Wnt signaling pathway. Furthermore, knocking down SFRP1 by RNA interfering in β-catenin-deficient cell lines (SK-Hep1) expressing SFRP1 stimulates Wnt signaling, promotes cell growth, and inhibits cancer invasion. Our results suggest that methylation silencing of SFRP1 may play an important role in aberrant Wnt activation in hepatomas. Our data also suggest that β-catenin-independent noncanonical pathway may be involved in the cell transformation caused by the activation of Wnt signaling.
Disease, and treatment / thematic poster session lung ultrasound b-lines are frequently found in two easily accessible imaging sites in COVID-19 and relate to disease severity: Implications for screening, triage and prognosis
Authors: R. Shi, E. M. Tran, P. M. Resnikoff, J. N. Phan, S. R. Spierling Bagsic, B. J. Kimura
Journal: American Journal of Respiratory and Critical Care Medicine (2021)

Rationale: Lung ultrasound B-lines artifacts represent abnormal interstitial thickening or edema, have been related to patient mortality, and are often visualized when imaging the anteroapex of the lung. Unlike other probe locations, these 2 sites on the upper chest can be readily accessed by healthcare givers and patients alike. In COVID-19 infection, the potential value of these sites for detecting early lung involvement depends not only on accessibility, but also on the relationship of its findings with significant disease. Therefore, as few ultrasound data exist from the lung apex in hospitalized COVID-19 pneumonia, we sought to report the prevalence of apical lung B-line artifacts in inpatients and their association with illness severity. Methods: In a 300-bed community hospital, medical and imaging data from inpatients with known COVID-19 infection who had been referred for echocardiography with lung imaging or who had received a lung point-of-care ultrasound study was reviewed for the presence of ≥3 B-lines (COMETS) in either anteroapex of the lungs. COVID-19 disease was categorized by the CDC Clinical Severity Scale on presentation as mild (no dyspnea, normal CXR/CT), moderate (abnormal CXR/CT, O2 sat>94%), severe (tachypnea, O2 sat  50%), or critical (respiratory failure, shock, multiorgan system failure). Age, gender, diabetes, hypertension, obesity, and time from onset of symptoms to the imaging study were analyzed for univariable associations with COMET presence and then considered with severity category in a reduced multivariable model using backwards elimination. Results: Of n=56 patients, age (mean±SD) was 63±16 years. COMETS were present in 35/56 (63%) of patients overall, and in 30/37 (81%) of severe-critical disease vs. 5/19 (26)% of mild-moderate disease (p=0.0002). Of the patients with vs. without COMETS, 31 (76%) vs. 10 (24%) had an abnormal CXR and 30 (79%) vs. 8 (21%) had O2 sat 80% in severe/critical disease. This imaging site, in particular, may be ideal for outpatient screening, ER triage, or patient home imaging, where it may herald the need for early respiratory diagnosis, therapies or hospitalization. Future studies involving the prevalence, timing and outcome of outpatient ultrasound lung imaging may consider the use of this easily-accessed site on the chest wall. .
Developmental Consequences of Defective ATG7-Mediated Autophagy in Humans
Authors: Jack J. Collier, Claire Guissart, Monika Oláhová, Souphatta Sasorith, Florence Piron-Prunier, Fumi Suomi, David Zhang, Nuria Martinez-Lopez, Nicolas Leboucq, Angela Bahr, Silvia Azzarello-Burri, Selina Reich, Ludger Schöls, Tuomo M. Polvikoski, Pierre Meyer, Lise Larrieu, Andrew M. Schaefer, Hessa S. Alsaif, Suad Alyamani, Stephan Zuchner, Inês A. Barbosa, Charu Deshpande, Angela Pyle, Anita Rauch, Matthis Synofzik, Fowzan S. Alkuraya, François Rivier, Mina Ryten, Robert McFarland, Agnès Delahodde, Thomas G. McWilliams, Michel Koenig, Robert W. Taylor
Journal: New England Journal of Medicine (2021)

Autophagy is the major intracellular degradation route in mammalian cells. Systemic ablation of core autophagy-related (ATG) genes in mice leads to embryonic or perinatal lethality, and conditional models show neurodegeneration. Impaired autophagy has been associated with a range of complex human diseases, yet congenital autophagy disorders are rare.
Variability of Nutritional Practices in Peritransplant Period after Allogeneic Hematopoietic Stem Cell Transplantation: A Survey By the Complications and Quality of Life Working Party of the EBMT
Authors: Zinaida Peric, Stefano Botti, Joanna Krawczyk, Steffie van der Werf, Anja van Biezen, Mahmoud Aljurf, John Murray, Jacqui Stringer, Sarah J Liptrott, Diana M Greenfield, Rafael F Duarte, Tapani Ruutu, Grzegorz W Basak
Journal: Blood (2017)
Myocarditis Following Immunization With mRNA COVID-19 Vaccines in Members of the US Military
Authors: Jay Montgomery, Margaret Ryan, Renata Engler, Donna Hoffman, Bruce McClenathan, Limone Collins, David Loran, David Hrncir, Kelsie Herring, Michael Platzer, Nehkonti Adams, Aliye Sanou, Leslie T. Cooper
Journal: JAMA Cardiology (2021)

Myocarditis has been reported with COVID-19 but is not clearly recognized as a possible adverse event following COVID-19 vaccination.To describe myocarditis presenting after COVID-19 vaccination within the Military Health System.This retrospective case series studied patients within the US Military Health System who experienced myocarditis after COVID-19 vaccination between January and April 2021. Patients who sought care for chest pain following COVID-19 vaccination and were subsequently diagnosed with clinical myocarditis were included.Receipt of a messenger RNA (mRNA) COVID-19 vaccine between January 1 and April 30, 2021.Clinical diagnosis of myocarditis after COVID-19 vaccination in the absence of other identified causes.A total of 23 male patients (22 currently serving in the military and 1 retiree; median [range] age, 25 [20-51] years) presented with acute onset of marked chest pain within 4 days after receipt of an mRNA COVID-19 vaccine. All military members were previously healthy with a high level of fitness. Seven received the BNT162b2-mRNA vaccine and 16 received the mRNA-1273 vaccine. A total of 20 patients had symptom onset following the second dose of an appropriately spaced 2-dose series. All patients had significantly elevated cardiac troponin levels. Among 8 patients who underwent cardiac magnetic resonance imaging within the acute phase of illness, all had findings consistent with the clinical diagnosis of myocarditis. Additional testing did not identify other etiologies for myocarditis, including acute COVID-19 and other infections, ischemic injury, or underlying autoimmune conditions. All patients received brief supportive care and were recovered or recovering at the time of this report. The military administered more than 2.8 million doses of mRNA COVID-19 vaccine in this period. While the observed number of myocarditis cases was small, the number was higher than expected among male military members after a second vaccine dose.In this case series, myocarditis occurred in previously healthy military patients with similar clinical presentations following receipt of an mRNA COVID-19 vaccine. Further surveillance and evaluation of this adverse event following immunization is warranted. Potential for rare vaccine-related adverse events must be considered in the context of the well-established risk of morbidity, including cardiac injury, following COVID-19 infection.
CRISPR-Cas9 In Vivo Gene Editing for Transthyretin Amyloidosis
Authors: Julian D. Gillmore, Ed Gane, Jorg Taubel, Justin Kao, Marianna Fontana, Michael L. Maitland, Jessica Seitzer, Daniel O’Connell, Kathryn R. Walsh, Kristy Wood, Jonathan Phillips, Yuanxin Xu, Adam Amaral, Adam P. Boyd, Jeffrey E. Cehelsky, Mark D. McKee, Andrew Schiermeier, Olivier Harari, Andrew Murphy, Christos A. Kyratsous, Brian Zambrowicz, Randy Soltys, David E. Gutstein, John Leonard, Laura Sepp-Lorenzino, David Lebwohl
Journal: New England Journal of Medicine (2021)

Transthyretin amyloidosis, also called ATTR amyloidosis, is a life-threatening disease characterized by progressive accumulation of misfolded transthyretin (TTR) protein in tissues, predominantly the nerves and heart. NTLA-2001 is an in vivo gene-editing therapeutic agent that is designed to treat ATTR amyloidosis by reducing the concentration of TTR in serum. It is based on the clustered regularly interspaced short palindromic repeats and associated Cas9 endonuclease (CRISPR-Cas9) system and comprises a lipid nanoparticle encapsulating messenger RNA for Cas9 protein and a single guide RNA targeting TTR.
mRNA therapeutics: beyond vaccine applications
Authors: Balkrishen Bhat, Shrirang Karve, Daniel G. Anderson
Journal: Trends in Molecular Medicine (2021)

The basic principle of mRNA therapeutics involves delivery of in vitro transcribed mRNA into a target cell, where cellular machinery translates the mRNA into a functional protein. In vaccine applications, an mRNA encoding a viral protein will elicit a protective immune response, whereas in therapeutic applications, an mRNA encoding an absent (or dysfunctional) protein in a patient provides functional protein expression. Thus, mRNAs can be widely used in vaccine development, protein replacement therapy, and the treatment of genetic diseases. Lipid nanoparticles (LNPs) are the most common delivery system being developed to effectively deliver mRNA medicines for many therapeutic indications, protecting the mRNA from degradation. The LNPs are customized for delivery to specific tissues, focusing on optimal size, surface charge, and lipid composition. Significant progress has been made in developing safe mRNA therapeutics for a number of disease indications. Enables druggability of intracellular, transmembrane, and secreted proteins. Restores gene expression without risk of genomic integration. Druglike behavior: ability to repeat dose and adjust dose/dose interval. Endogenous post-transcriptional modifications increase probability of correct folding, glycosylation, and trafficking of the protein and decrease risk of immunogenicity. Minimal changes to the manufacturing process for multiple targets. Rapid development from target gene selection to product candidate. Stability: mRNA is susceptible to degradation. Delivery: LNPs must be tissue-specific and biodegradable. Immunogenicity: risk of activating the immune system via Toll-like and retinoic acid–inducible gene–like receptors. Manufacturing: difficult to achieve high quality and highly pure mRNA with scalable manufacturing processes/ Because of the central role of mRNA in protein expression, mRNA technology has broad applicability in the treatment or prevention of disease. Two mRNA-based coronavirus disease 2019 (COVID-19) vaccines have Emergency Use Authorization, demonstrating the clinical validation of this revolutionary approach. mRNA replacement therapy for genetic diseases is being developed for lung and liver diseases (inhaled and intravenous delivery). Immuno-oncologic approaches can leverage the intrinsic immune adjuvant effects of mRNA. The authors have no interests to declare.
Spying on the Polarity Dynamics during Wound Healing of Zebrafish by Using Rationally Designed Carbon Dots
Authors: Jingyu Hu, Ran Yang, Haoyue Qin, Yuanqiang Sun, Lingbo Qu, Zhaohui Li
Journal: Advanced Healthcare Materials (2021)

Abstract Wound healing is an essential and complex biological process. Research into its mechanism and factors that influence its effectiveness has led to better treatments. Changes in the microenvironment are demonstrated to affect wound healing. Cell polarity is a significant microenvironment‐related parameter that is associated with many physiological and pathological activities. However, dynamic changes in polarity during wound healing have not been investigated. Monitoring cell polarity during wound healing may open up a new avenue for developing better treatments. Here, a method is developed to monitor cell polarity that involved taking advantage of the fascinating optical properties and biocompatibility of carbon dots (CDs). Specifically, near‐infrared (NIR) polarity‐sensitive N‐phenyl‐p‐phenylenediamine (PPh‐CDs) are successfully prepared, which exhibit high sensitivity to polarity, with 509‐fold stronger fluorescence in dioxane than in water. The PPh‐CDs are successfully applied to monitor the changes of lysosomal polarity during starvation conditions. Using this method, dynamic changes of polarity during wound healing of zebrafish are monitored for the first time. Upon an amputation performed at the zebrafish tail, stronger PPh‐CDs fluorescence appeared at the wound sites, and the intensity increased for 25 min and then gradually decreased. This report provides an important experimental basis for investigating wound healing by employing polarity‐sensitive CDs.
Patients Responding to Any First Line Therapy for Multiple Myeloma Should Proceed to Autologous Stem Cell Transplantation Instead of Receiving Second Line Therapy to Deepen Response
Authors: Nino Aleksidze, Phyllis McKiernan, David Siegel, Scott D. Rowley, David H. Vesole, Tracy Andrews, Andrea Ortega, Alan P Skarbnik, Noa Biran, Joshua R Richter, Andrew L. Pecora, Andre Goy, Rima M Panchal, Michele L. Donato
Journal: Blood (2017)
Prognostic Impact of Metabolic Heterogeneity in Patients With Newly Diagnosed Multiple Myeloma Using 18F-FDG PET/CT
Authors: Toshiki Terao, Youichi Machida, Kenji Hirata, Ayumi Kuzume, Rikako Tabata, Takafumi Tsushima, Daisuke Miura, Kentaro Narita, Masami Takeuchi, Ukihide Tateishi, Kosei Matsue
Journal: Clinical Nuclear Medicine (2021)

Purpose This study aimed to investigate the prognostic impact of metabolic heterogeneity (MH) in patients with multiple myeloma (MM). Patients and Methods We retrospectively analyzed MH with 18 F-FDG PET/CT in 203 patients with newly diagnosed MM. Metabolic heterogeneity was estimated using the area under the curve of the cumulative SUV volume histogram. To evaluate MH, we selected 2 lesions: “MH-SUV max ,” a lesion with SUV max , and “MH–metabolic tumor volume (MTV),” a lesion with the largest MTV. Results Metabolic heterogeneity from an MH-SUV max lesion showed more prognostic relevance than that from a lesion with the largest MTV. The progression-free survival (PFS) and overall survival (OS) rates were significantly lower in the high-MH-SUV max group than in the low-MH-SUV max group (median PFS: 25.2 vs 33.9 months; median OS: 41.6 vs 112.0 months; P = 0.004 and 0.046, respectively), whereas high MH-SUV max retained independent prognostic power on multivariate analysis. Even among patients with high whole-body MTV, those with high MH-SUV max tended to show poorer prognosis than those without (median PFS, 23.8 vs 30.2 months; P = 0.085). Moreover, patients with high MH-SUV max and high-risk cytogenetic abnormalities showed dismal outcomes even with standard treatment (median PFS and OS, 10.0 and 33.3 months, respectively). Conclusions Our results suggested that high MH-SUV max based on pretreatment with 18 F-FDG PET/CT is a novel prognostic factor for cases of MM.
Induction of EBV latent membrane protein-2A (LMP2A)-specific T cells and construction of individualized TCR-engineered T cells for EBV-associated malignancies
Authors: Chaoting Zhang, Qin Tan, Shance Li, Luyan Shen, Jingtao Zhang, Ying Liu, Wenjun Yang, Zheming Lu
Journal: Journal for ImmunoTherapy of Cancer (2021)

Background Latent membrane protein-2A (LMP2A)-specific TCR-engineered T cells could be a promising treatment approach to Epstein–Barr virus-associated malignancies. However, previous studies mainly reported LMP2A-reactive TCRs only focusing on specific HLA subtypes and corresponding epitopes, and thus, they were only suitable for patients with specific HLA. Methods Due to hugely varied HLA subtypes and presented LMP2A epitopes in different individuals, our study attempted to develop an individualized approach, based on the weekly in vitro stimulation of peripheral T cells for 2 weeks with autologous dendritic cells (DCs) pulsed with a pool of LMP2A peptides covering LMP2A whole protein and combination analysis of high throughput TCRβ sequencing of prestimulated and poststimulated T cells and single-cell TCR sequencing of poststimulated T cells, and to identify LMP2A-specific TCRs of which poststimulated frequencies significantly increased than corresponding prestimulated frequencies. Results Following this approach, multiple LMP2A-reactive TCRs were identified, optimized and cloned into lentiviral vector, and then transduced into peripheral T cells. These engineerd T cells were demonstrated to specifically recognize the LMP2A presented by autologous DCs and lymphoblastoid cell lines in vitro and in vivo. Conclusions This approach provides an efficient procedure to isolate individualized LMP2A-specific TCRs for basic and translational research, as well as for clinical applications.