tbuckley/cabot-search huggingface dataset:
Education, Implementation, and Teams: 2020 International Consensus on Cardiopulmonary Resuscitation and Emergency Cardiovascular Care Science With Treatment Recommendations
Authors: Robert Greif, Farhan Bhanji, Blair L. Bigham, Janet Bray, Jan Breckwoldt, Adam Cheng, Jonathan P. Duff, Elaine Gilfoyle, Ming-Ju Hsieh, Taku Iwami, Kasper G. Lauridsen, Andrew S. Lockey, Matthew Huei-Ming Ma, Koenraad G. Monsieurs, Deems Okamoto, Jeffrey L. Pellegrino, Joyce Yeung, Judith C. Finn, Enrico Baldi, Stefanie Beck, Stefan K. Beckers, Audrey L. Blewer, Adam Boulton, Liu Cheng-Heng, Chi-Wie Yang, Alison Coppola, Katie N. Dainty, Domagoj Damjanovic, Therese Djärv, Aaron Donoghue, Marios Georgiou, Imogen Gunson, Jamillee L. Krob, Artem Kuzovlev, Ying-Chih Ko, Marion Leary, Yiqun Lin, Mary E. Mancini, Tasuku Matsuyama, Kenneth Navarro, Ziad Nehme, Aaron M. Orkin, Tommaso Pellis, Lucas Pflanzl-Knizacek, Luca Pisapia, Michela Saviani, Taylor Sawyer, Andrea Scapigliati, Sebastian Schnaubelt, Barnaby Scholefield, Federico Semeraro, Salma Shammet, Michael A. Smyth, Abigail Ward, Drieda Zace
Journal: Circulation (2020)

For this 2020 International Consensus on Cardiopulmonary Resuscitation and Emergency Cardiovascular Care Science With Treatment Recommendations, the Education, Implementation, and Teams Task Force applied the population, intervention, comparator, outcome, study design, time frame format and performed 15 systematic reviews, applying the Grading of Recommendations, Assessment, Development, and Evaluation guidance. Furthermore, 4 scoping reviews and 7 evidence updates assessed any new evidence to determine if a change in any existing treatment recommendation was required. The topics covered included training for the treatment of opioid overdose; basic life support, including automated external defibrillator training; measuring implementation and performance in communities, and cardiac arrest centers; advanced life support training, including team and leadership training and rapid response teams; measuring cardiopulmonary resuscitation performance, feedback devices, and debriefing; and the use of social media to improve cardiopulmonary resuscitation application.
The role of p53 and p21 in cancer therapy with MDM2 inhibitor.
Authors: Mianen Sun, Zhuo Zhang, Gautam Prasad, Ying Wang, Sudhir Agrawal, Ruiwen Zhang, Hui Wang
Journal: Cancer Research (2004)

3635  MDM2 is amplified or overexpressed in many human malignancies and high MDM2 levels are associated with poor prognosis. We and others have shown that MDM2 may be a valuable target for human cancer therapy. Recently, we have developed a second-generation antisense oligonucleotide targeting human MDM2 mRNA, which has demonstrated antitumor activity in more than 15 cell lines and xenografts of human cancers with various p53 statuses (Clin. Cancer. Res. 2001; 7, 3613-3624; Mol. Med.2002,8, 185–199; Prostate 2003,54, 194–205; PNAS 2003,100, 11636–11641). These results further confirm that MDM2 has both p53-dependent and p53-independent activities. In addition, up-regulation of p21WAF1/CIP1 has consistently been observed following MDM2 inhibition, regardless of p53 status. The present study was designed to determine the role of p53 and p21 in the therapeutic effectiveness of the MDM2 inhibitor, using four genetically modified HCT116 colon cancer cell lines with various p53 and p21 gene backgrounds, parental (p53+/+ and p21+/+), p53 knockout (KO) (p53−/−), p21 KO (p21−/− ), and p53 and p21 double KO (p53−/− and p21−/−) cells. At least five novel and significant results were generated. First, in a dose-dependent manner, the antisense oligonucleotide specifically inhibited MDM2 expression in all cell lines. Second, compared with parental cells, the p53 KO cells were less sensitive to the anti-MDM2 antisense oligonucleotide, as measured by in vitro cell growth, proliferation, and apoptosis assays. Compared with p21 KO cells, p53/p21 double KO cells showed less sensitivity to anti-MDM2 antisense treatment in vitro. Third, overexpression of MDM2 by transfection of pcDNA3-MDM2 significantly decreased p21 levels in parental and p53 KO cells, promoting proliferation and inhibiting apoptosis. Fourth, the in vivo study demonstrated that p53 KO and p21 KO xenografts were less responsive to antisense MDM2 oligonucleotide compared with parental cells. The p53/p21 double KO cells were the fastest growing xenografts among the test cells and also less responsive to MDM2 inhibition. Fifth, compared to parental cells, p53 KO cells were resistant to radiation treatment in vitro and in vivo. In summary, we provide evidence supporting the importance of p53 and p21 in therapy with an antisense MDM2 inhibitor. These newly identified mechanisms may have potential in the development of novel anticancer agents. (Supported by NIH/NCI grant CA80698.)
Combined genetic analysis of juvenile idiopathic arthritis clinical subtypes identifies novel risk loci, target genes and key regulatory mechanisms
Authors: Elena López-Isac, Samantha L Smith, Miranda C Marion, Abigail Wood, Marc Sudman, Annie Yarwood, Chenfu Shi, Vasanthi Priyadarshini Gaddi, Paul Martin, Sampath Prahalad, Stephen Eyre, Gisela Orozco, Andrew P Morris, Carl D Langefeld, Susan D Thompson, Wendy Thomson, John Bowes
Journal: Annals of the Rheumatic Diseases (2020)

Juvenile idiopathic arthritis (JIA) is the most prevalent form of juvenile rheumatic disease. Our understanding of the genetic risk factors for this disease is limited due to low disease prevalence and extensive clinical heterogeneity. The objective of this research is to identify novel JIA susceptibility variants and link these variants to target genes, which is essential to facilitate the translation of genetic discoveries to clinical benefit.
TCT CONNECT-243 Hospitalization Rates Before and After Percutaneous Coronary Intervention for Chronic Total Occlusion. A Nationwide Cohort Sample
Authors: Ahmed Elkaryoni, Ivo Genev, Adel Muhanna, Kirolos Barssoum, Islam Abdelkarim, Anne Arnason, Amir Darki
Journal: Journal of the American College of Cardiology (2020)
TCT CONNECT-232 Development and Validation of Prediction Model of Angiographic Perforation During Chronic Total Occlusion Percutaneous Coronary Intervention: Open-Clean Score
Authors: Taishi Hirai, J. Aaron Grantham, James Sapontis, William Nicholson, William Lombardi, Dimitrios Karmpaliotis, Jeffrey Moses, Kensey Gosch, Adam Salisbury
Journal: Journal of the American College of Cardiology (2020)
Flexible Bronchoscopic Thrombus Cryoextraction in a Neonate on Extracorporeal Membrane Oxygenation
Authors: John J. Brewington, Dan T. Benscoter, Cherie A. Torres-Silva, Carolyn M. McHendry, Foong-Yen Lim, DonnaMaria E. Cortezzo, Erik B. Hysinger
Journal: American Journal of Respiratory and Critical Care Medicine (2020)

"Flexible Bronchoscopic Thrombus Cryoextraction in a Neonate on Extracorporeal Membrane Oxygenation." American Journal of Respiratory and Critical Care Medicine, 203(5), pp. 633–635
Dietary cellulose induces anti-inflammatory immunity and transcriptional programs via maturation of the intestinal microbiota
Authors: Florence Fischer, Rossana Romero, Anne Hellhund, Uwe Linne, Wilhelm Bertrams, Olaf Pinkenburg, Hosam Shams Eldin, Kai Binder, Ralf Jacob, Alesia Walker, Bärbel Stecher, Marijana Basic, Maik Luu, Rouzbeh Mahdavi, Anna Heintz-Buschart, Alexander Visekruna, Ulrich Steinhoff
Journal: Gut Microbes (2020)

Although it is generally accepted that dietary fiber is health promoting, the underlying immunological and molecular mechanisms are not well defined, especially with respect to cellulose, the most ubiquitous dietary fiber. Here, the impact of dietary cellulose on intestinal microbiota, immune responses and gene expression in health and disease was examined. Lack of dietary cellulose disrupted the age-related diversification of the intestinal microbiota, which subsequently remained in an immature state. Interestingly, one of the most affected microbial genera was Alistipes which is equipped with enzymes to degrade cellulose. Absence of cellulose changed the microbial metabolome, skewed intestinal immune responses toward inflammation, altered the gene expression of intestinal epithelial cells and mice showed increased sensitivity to colitis induction. In contrast, mice with a defined microbiota including A. finegoldii showed enhanced colonic expression of intestinal IL-22 and Reg3γ restoring intestinal barrier function. This study supports the epidemiological observations and adds a causal explanation for the health promoting effects of the most common biopolymer on earth.
Isatuximab as monotherapy and combined with dexamethasone in patients with relapsed/refractory multiple myeloma
Authors: Meletios Dimopoulos, Sara Bringhen, Pekka Anttila, Marcelo Capra, Michele Cavo, Craig Cole, Cristina Gasparetto, Vania Hungria, Matthew Jenner, Vladimir Vorobyev, Eduardo Yanez Ruiz, Jian Y. Yin, Rao Saleem, Maeva Hellet, Sandrine Macé, Bruno Paiva, Ravi Vij
Journal: Blood (2020)
RAAS Inhibitors and Risk of Covid-19
Authors: Martin H Strauss, Alistair S Hall, Carl J Lavie
Journal: New England Journal of Medicine (2020)

tent with a drug-induced process 3 but rather with the patients' underlying disease.Treatment with givosiran was associated with small increases in creatinine (0.07 mg per deciliter at 3 months) in the overall trial population, changes that were mainly reversible.Some patients with preexisting renal disease had reductions in renal function that stabilized with ongoing administration of givosiran.However, consistent with labeling, monitoring of renal function during givosiran treatment is recommended as clinically indicated.
Recurrent Malignant Pheochromocytoma With Unusual Peritoneal Carcinomatosis Detected on 131I-MIBG SPECT/CT
Authors: Hui Wang, Junjun Cheng, Xiaohong Ou
Journal: Clinical Nuclear Medicine (2020)

The most common sites of metastasis for pheochromocytoma are the lymph nodes, bones, lungs, and liver. Peritoneal metastasis or implantation is very rare. We present a case of recurrent malignant pheochromocytoma with unusual multiple peritoneal carcinomatosis on I-MIBG SPECT/CT after laparoscopic adrenalectomy.
TCT CONNECT-480 Impact of Cusp-Overlap Technique on Pacemaker Requirement among Patients Receiving Transcatheter Aortic Valve Replacement
Authors: Matias Sztejfman, Carlos Giuliani, Ezequiel Zaidel, Sebastian Peralta, Guillermo Jubany, Luis Murillo, José Rojas, Juan Grieve, Carlos Sztejfman, Marcelo Bettinotti
Journal: Journal of the American College of Cardiology (2020)
TCT CONNECT-462 Temporal Incidence and Predictors of High-Grade Atrioventricular Block After Transcatheter Aortic Valve Replacement
Authors: Bassim El-Sabawi, Garrett Welle, Yong-Mei Cha, Raul Espinosa, Rajiv Gulati, Gurpreet Sandhu, Kevin Greason, Juan Crestanello, Paul Friedman, Thomas Munger, Chet Rihal, Mackram Eleid
Journal: Journal of the American College of Cardiology (2020)
TCT CONNECT-139 Hemodynamic Comparison of Transcatheter Aortic Valve Replacement With the SAPIEN 3 Ultra Versus SAPIEN 3: The HomoSAPIEN Registry
Authors: Noriaki Moriyama, Heidi Lehtola, Hirokazu Miyashita, Jarkko Piuhola, Matti Niemela, Mika Laine
Journal: Journal of the American College of Cardiology (2020)
Antibacterial Hydrogels: Injectable and Self‐Healing Hydrogel with Anti‐Bacterial and Anti‐Inflammatory Properties for Acute Bacterial Rhinosinusitis with Micro Invasive Treatment (Adv. Healthcare Mater. 20/2020)
Authors: Zhengming Chen, Zhengwei Cai, Chengjing Zhu, Xianmin Song, Yanghua Qin, Minhui Zhu, Tao Zhang, Wenguo Cui, Haihong Tang, Hongliang Zheng
Journal: Advanced Healthcare Materials (2020)

In article number 2001032 by Haihong Tang, Hongliang Zheng, and co-workers, an injectable and self-healing hydrogel is first developed to treat acute bacterial rhinosinusitis based on high affinity and reversible combination between thiol and Ag+. This dynamic hydrogel with antibacterial and anti-inflammatory properties is suitable for sinus micro invasive treatment which not only effectively eliminates pathogens, but also reduces mucosal edema. This approach provides a new strategy for avoiding systemic abuse of antibiotics.
TCT CONNECT-233 Coronary Artery Perforations in Patients Treated Using Percutaneous Coronary Interventions Within Chronic Total Occlusions: Analysis Based on a Large National Registry
Authors: Leszek Bryniarski, Zbigniew Siudak, Krzysztof Malinowski, Slawomir Surowiec, Aleksander Zelias, Roman Wojdyla, Krzysztof Bryniarski, Magdalena Jędrychowska, Dominika Dykla, Wojciech Wańha, Krzysztof Bartus, Wojciech Wojakowski, Jaroslaw Wojcik, Jacek Legutko, Andrzej Surdacki, Stanisław Bartuś, Rafał Januszek
Journal: Journal of the American College of Cardiology (2020)
Home treatment of pulmonary embolism: are all the questions answered now after the HOME-PE trial?
Authors: Stavros V Konstantinides
Journal: Cardiovascular Research (2020)

Pulmonary • sPESI • Hestia • thrombosis With annual incidence rates ranging between 39 and 115 per 100 000 population, 1 acute pulmonary embolism (PE) is the third most frequent acute cardiovascular syndrome after myocardial infarction and stroke.Importantly, both the incidence rates of venous thromboembolism and the PE-related mortality rates rise exponentially among the elderly, 2,3 which is an alarming fact in view of the progressive ageing of the population in most countries.Fortunately, only a minority of all cases of acute PE are lifethreatening.In fact, clinical severity ranges from haemodynamic collapse due to fulminant right ventricular (RV) failure to mildly symptomatic disease or even an incidental finding on a computer tomogram performed for another indication.It is therefore crucial that management strategies for acute PE take into account its broad risk spectrum in order to ensure appropriate allocation of hospital resources to the patients who urgently need them, while allowing for early discharge of those who can be treated at home safely.If feasible and safe, treatment outside the hospital can minimize hospitalization-related complications, reduce healthcare costs, and improve the patients' quality of life.Following these principles, the recent (2019) update of the European Society of Cardiology (ESC) Guidelines for acute PE, developed in collaboration with the European Respiratory Society (ERS), elaborated a risk-adjusted stepwise approach to PE treatment. 4pecifically, criteria for identifying patients whose risk is 'sufficiently low' to permit early discharge and ambulatory treatment were proposed, based on the results of trials conducted in the vitamin K antagonist era 5,6 and on more recent data. 7,8However, while awaiting the impact of these recommendations on clinical practice, we continue to to acknowledge that most of the patients with acute PE currently admitted to large European centres spend (far) more than 5 days in hospital. 2,9The Hospitalization or Outpatient Management of Patients with Pulmonary Embolism (HOME-PE) study, recently presented at the ESC Congress 2020, may provide some helpful insights on the way to improve this situation.HOME-PE was an investigator-initiated multicentre prospective management trial, aiming to compare two sets of clinical criteria, the simplified version of the Pulmonary Embolism Severity Index (sPESI) and the Hestia rule, in their ability to identify the 'optimal' candidates for early discharge among patients with acute PE.The key features of the study design are shown in Table 1.It is important to highlight some aspects that determined the flow and the results of the trial:
We must be cautious when reintroducing appraisal and revalidation for UK doctors
Authors: Carter Singh
Journal: BMJ (2020)

Although the relaxed approach to appraisal and revalidation has been a welcome respite for most hardworking doctors in the challenging times of the covid-19 pandemic, we need to be acutely aware that any overbearing or bureaucratic aspects of regulation are reintroduced with caution when we may be …
Preventive digital mental health interventions for children and young people: a review of the design and reporting of research
Authors: Aislinn D. Bergin, Elvira Perez Vallejos, E. Bethan Davies, David Daley, Tamsin Ford, Gordon Harold, Sarah Hetrick, Megan Kidner, Yunfei Long, Sally Merry, Richard Morriss, Kapil Sayal, Edmund Sonuga-Barke, Jo Robinson, John Torous, Chris Hollis
Journal: npj Digital Medicine (2020)

Digital health interventions (DHIs) have frequently been highlighted as one way to respond to increasing levels of mental health problems in children and young people. Whilst many are developed to address existing mental health problems, there is also potential for DHIs to address prevention and early intervention. However, there are currently limitations in the design and reporting of the development, evaluation and implementation of preventive DHIs that can limit their adoption into real-world practice. This scoping review aimed to examine existing evidence-based DHI interventions and review how well the research literature described factors that researchers need to include in their study designs and reports to support real-world implementation. A search was conducted for relevant publications published from 2013 onwards. Twenty-one different interventions were identified from 30 publications, which took a universal (n = 12), selective (n = 3) and indicative (n = 15) approach to preventing poor mental health. Most interventions targeted adolescents, with only two studies including children aged ≤10 years. There was limited reporting of user co-design involvement in intervention development. Barriers and facilitators to implementation varied across the delivery settings, and only a minority reported financial costs involved in delivering the intervention. This review found that while there are continued attempts to design and evaluate DHIs for children and young people, there are several points of concern. More research is needed with younger children and those from poorer and underserved backgrounds. Co-design processes with children and young people should be recognised and reported as a necessary component within DHI research as they are an important factor in the design and development of interventions, and underpin successful adoption and implementation. Reporting the type and level of human support provided as part of the intervention is also important in enabling the sustained use and implementation of DHIs.
TCT CONNECT-356 Incidence of New-Onset Atrial Fibrillation Following Transcatheter Mitral Valve Repair: Insights From the Nationwide Readmissions Database
Authors: Fabio Lima, Kevin Kennedy, Dhaval Kolte, Marwan Saad, Chirag Bavishi, Eyal Ben-Assa, Anshul Parulkar, Wasiq Sheikh, Igor Palacios, Paul Gordon, Antony Chu
Journal: Journal of the American College of Cardiology (2020)
TCT CONNECT-167 Comparison of Stent Expansion Between Xience and Orsiro Stents in Heavily Calcified Coronary Arteries in Cadaver Heart
Authors: Yu Sato, Hiroyuki Jinnouchi, Atsushi Sakamoto, Anne Cornelissen, Masayuki Mori, Rika Kawakami, Kenji Kawai, Laura Perkins, Renu Virmani, Aloke Finn
Journal: Journal of the American College of Cardiology (2020)
Clinico-Radio-Pathological and Molecular Features of Hepatocellular Carcinomas with Keratin 19 Expression
Authors: Hyungjin Rhee, Haeryoung Kim, Young Nyun Park
Journal: Liver Cancer (2020)

Hepatocellular carcinoma (HCC) is a heterogeneous neoplasm, both from the molecular and histomorphological aspects. One example of heterogeneity is the expression of keratin 19 (K19) in a subset (4–28%) of HCCs. The presence of K19 expression in HCCs has important clinical implications, as K19-positive HCCs have been associated with aggressive tumor biology and poor prognosis. Histomorphologically, K19-positive HCCs demonstrate a more infiltrative appearance, poor histological differentiation, more frequent vascular invasion, and more intratumoral fibrous stroma than K19-negative conventional HCCs. From the molecular aspect, K19-positive HCCs have been matched with various gene signatures that have been associated with stemness and poor prognosis, including the G1–3 groups, S2 class, cluster A, proliferation signature, and vascular invasion signature. K19-positive HCCs also show upregulated signatures related to transforming growth factor-β pathway and epithelial-to-mesenchymal transition. The main regulators of K19 expression include hepatocyte growth factor-MET paracrine signaling by cancer-associated fibroblast, epidermal growth factor-epidermal growth factor receptor signaling, laminin, and DNA methylation. Clinically, higher serum alpha-fetoprotein levels, frequent association with chronic hepatitis B, more invasive growth, and lymph node metastasis have been shown to be characteristics of K19-positive HCCs. Radiologic features including atypical enhancement patterns, absence of tumor capsules, and irregular tumor margins can be a clue for K19-positive HCCs. From a therapeutic standpoint, K19-positive HCCs have been associated with poor outcomes after curative resection or liver transplantation, and resistance to systemic chemotherapy and locoregional treatment, including transarterial chemoembolization and radiofrequency ablation. In this review, we summarize the currently available knowledge on the clinico-radio-pathological and molecular features of K19-expressing HCCs, including a detailed discussion on the regulation mechanism of these tumors.
Additional Concerns Regarding Children With Coronavirus Disease 2019
Authors: Danni He, Qi Zhang
Journal: JAMA Pediatrics (2020)

Riccardo Castagnoli, MD; Martina Votto, MD; Amelia Licari, MD; Ilaria Brambilla, MD, PhD; Raffaele Bruno, MD; Stefano Perlini, MD; Francesca Rovida, PhD; Fausto Baldanti, MD; Gian Luigi Marseglia, MD
Mucosal‐Associated Invariant T Cell Dysregulation Correlates With Conjugated Bilirubin Level in Chronic HBV Infection
Authors: Yu Liu, Peng Zhu, Wei Wang, Xiaosheng Tan, Chuanqiao Liu, Yingshan Chen, Rongjuan Pei, Xue Cheng, Mi Wu, Qing Guo, Hongmei Liang, Zhihui Liang, Jia Liu, Yang Xu, Xiongwen Wu, Xiufang Weng
Journal: Hepatology (2020)

Mucosal-associated invariant T (MAIT) cells are nonconventional T cells restricted to major histocompatibility complex class I-related protein 1 (MR1). They are highly abundant in human liver and activated by T-cell receptor (TCR)-dependent and TCR-independent mechanisms to exhibit rapid, innate-like effector responses. However, the roles of MAIT cells in chronic HBV infection are still open for study. This study aims to test their antiviral potential and investigate their dynamic changes and regulating factors during chronic HBV infection.Blood samples from 257 chronic HBV-infected patients were enrolled, and nontumor liver specimens were collected from 58 HBV-infected HCC patients. Combining cell-culture experiments and human data, we showed that MAIT cells had strong cytotoxicity against HBV-transfected hepatocytes in an MR1-dependent way. However, circulating and hepatic MAIT cells in HBV-infected patients decreased significantly compared to controls. Correlation analysis suggested that MAIT cell frequency was associated with disease progression and inversely correlated with serum-conjugated bilirubin level. In particular, conjugated bilirubin not only directly promoted MAIT cell activation and apoptosis, but also impaired TCR-induced proliferation and expansion of MAIT cells, which could be partially rescued by IL-2 in the absence of conjugated bilirubin. Despite that MAIT cells from patients with high conjugated bilirubin levels showed decreased cytokine-producing capacity, the increased TCR-dependent antiviral cytokine production suggested MAIT cells as an important guardian of chronic HBV with high conjugated bilirubin.We reveal the MR1-dependent, anti-HBV potential of MAIT cells and identify conjugated bilirubin as a major factor dysregulating its frequency and function in chronic HBV-infected patients, suggesting a therapeutic target for MAIT-cell-based immunity against chronic HBV infection.