tbuckley/cabot-search huggingface dataset:
Vaccine effectiveness against symptomatic SARS-CoV-2 infection in adults aged 65 years and older in primary care: I-MOVE-COVID-19 project, Europe, December 2020 to May 2021
Authors: Esther Kissling, Mariette Hooiveld, Virginia Sandonis Martín, Iván Martínez-Baz, Naoma William, Ana-Maria Vilcu, Clara Mazagatos, Lisa Domegan, Simon de Lusignan, Adam Meijer, Ausenda Machado, Mia Brytting, Itziar Casado, Josephine-L K. Murray, Sylvie Belhillil, Amparo Larrauri, Joan O’Donnell, Ruby Tsang, Marit de Lange, Ana Paula Rodrigues, Maximilian Riess, Jesús Castilla, Mark Hamilton, Alessandra Falchi, Francisco Pozo, Linda Dunford, Jade Cogdale, Tessa Jansen, Raquel Guiomar, Theresa Enkirch, Cristina Burgui, Debbie Sigerson, Thierry Blanchon, Eva María Martínez Ochoa, Jeff Connell, Joanna Ellis, Rianne van Gageldonk-Lafeber, Irina Kislaya, Angela MC Rose, Marta Valenciano
Journal: Eurosurveillance (2021)

We measured COVID-19 vaccine effectiveness (VE) against symptomatic SARS-CoV-2 infection at primary care/outpatient level among adults ≥ 65 years old using a multicentre test-negative design in eight European countries. We included 592 SARS-CoV-2 cases and 4,372 test-negative controls in the main analysis. The VE was 62% (95% CI: 45–74) for one dose only and 89% (95% CI: 79–94) for complete vaccination. COVID-19 vaccines provide good protection against COVID-19 presentation at primary care/outpatient level, particularly among fully vaccinated individuals.
TRIM8 modulates the EWS/FLI oncoprotein to promote survival in Ewing sarcoma
Authors: Bo Kyung A. Seong, Neekesh V. Dharia, Shan Lin, Katherine A. Donovan, Shasha Chong, Amanda Robichaud, Amy Conway, Amanda Hamze, Linda Ross, Gabriela Alexe, Biniam Adane, Behnam Nabet, Fleur M. Ferguson, Björn Stolte, Emily Jue Wang, Jialin Sun, Xavier Darzacq, Federica Piccioni, Nathanael S. Gray, Eric S. Fischer, Kimberly Stegmaier
Journal: Cancer Cell (2021)

Fusion-transcription factors (fusion-TFs) represent a class of driver oncoproteins that are difficult to therapeutically target. Recently, protein degradation has emerged as a strategy to target these challenging oncoproteins. The mechanisms that regulate fusion-TF stability, however, are generally unknown. Using CRISPR-Cas9 screening, we discovered tripartite motif-containing 8 (TRIM8) as an E3 ubiquitin ligase that ubiquitinates and degrades EWS/FLI, a driver fusion-TF in Ewing sarcoma. Moreover, we identified TRIM8 as a selective dependency in Ewing sarcoma compared with >700 other cancer cell lines. Mechanistically, TRIM8 knockout led to an increase in EWS/FLI protein levels that was not tolerated. EWS/FLI acts as a neomorphic substrate for TRIM8, defining the selective nature of the dependency. Our results demonstrate that fusion-TF protein stability is tightly regulated and highlight fusion oncoprotein-specific regulators as selective therapeutic targets. This study provides a tractable strategy to therapeutically exploit oncogene overdose in Ewing sarcoma and potentially other fusion-TF-driven cancers.
Abstract 17503: Role of Blood Coagulation Factor V Expressed by Vascular Smooth Muscle Cells in vascular Remodeling
Authors: Poorna R Karuparthi, Tammy Strawn, Qiong Zhang, William Fay, Hongmin Sun
Journal: Circulation (2011)

Introduction - Blood coagulation factor V (fV) is synthesized in liver and present in blood, where it plays a central role in blood coagulation. FV is also expressed by cultured vascular smooth muscle cells (VSMC), and fV antigen has been detected in atherosclerotic plaque, suggesting that extrahepatic expression of fV plays an important role in vascular wall function and disease. However, very little is known about the functional impact of fV expression by VSMC, and it is unknown if fV is expressed locally within the arterial wall in vivo. Methods - We generated transgenic (Tg) mice with liver-specific fV transgene expression and crossed them to mice carrying a null fV mutation (fV +/- mice) to generate Tg rescue mice lacking native expression of fV (Tg+ fV -/- ). We isolated, cultured, and characterized aortic VSMC from Tg + fV -/- mice and compared results to control Tg + fV +/+ or wild-type (C57BL/6J) mouse VSMC. We studied the effect of fV expression on VSMC proliferation in vitro, and used reverse transcriptase (RT) PCR to assess fV expression in murine aorta. Results VSMC from Tg + fV +/+ mice proliferated faster than Tg + fV -/- VSMC, at time points ranging from 24-96 hrs (Absorbance values, as noted with MTT assay, at all time points were statistically significant; at 48 hrs, Tg + fV +/+ vs Tg + fV -/- , n = 4; P &lt;0.001). Cell cycle analysis with flowcytometry suggested that there were fewer cells in active division phases at different time points in the Tg + fV -/- VSMC. The difference in VSMC proliferation rates between groups persisted in the presence of hirudin, a potent and highly specific thrombin inhibitor (P &lt; 0.05). RT-PCR demonstrated that fV was expressed in both WT mouse cultured VSMC and aortic tissue in vivo. Conclusions - Expression of fV by VSMC promotes cell proliferation. This effect appears to be partly mediated not only by downstream thrombin, which activates VSMC, but also by a thrombin independent mechanism. fV is expressed in vivo in vascular tissue. These results offer important insights into the biological effects of fV and suggest that it has vascular functions distinct from its role in blood coagulation.
Long-term live-cell lipid droplet-targeted biosensor development for nanoscopic tracking of lipid droplet-mitochondria contact sites
Authors: Chengying Zhang, Huarong Shao, Jie Zhang, Xinyan Guo, Yue Liu, Zhigang Song, Fei Liu, Peixue Ling, Longguang Tang, Kang-Nan Wang, Qixin Chen
Journal: Theranostics (2021)

Background: Lipid droplets (LDs) establish a considerable number of contact sites with mitochondria to enable energy transfer and communication. In this study, we developed a fluorescent biosensor to image LD-mitochondria interactions at the nanoscale and further explored the function of LD-mediated matrix transmission in processes involving multi-organelle interactions. Methods: A fluorescent probe called C-Py (C21H19N3O2, 7-(diethylamino) coumarin-3-vinyl-4-pyridine acetonitrile) was designed and synthesized. Colocalization of C-Py and the commercial LD stain Nile Red was analyzed in HeLa cells. The fluorescence stability and signal to background ratio of C-Py under structured illumination microscopy (SIM) were compared to those of the commercial probe BODIPY493/503. The cytotoxicity of C-Py was assessed using CCK-8 assays. The uptake pattern of C-Py in HeLa cells was then observed under various temperatures, metabolic levels, and endocytosis levels. Contact sites between LDs and various organelles, such as mitochondria, nuclei, and cell membrane, were imaged and quantitated using SIM. Physical changes to the contact sites between LDs and mitochondria were monitored after lipopolysaccharide induction. Results: A LD-targeted fluorescent biosensor, C-Py, with good specificity, low background signal, excellent photostability, low cytotoxicity, and high cellular permeability was developed for tracking LD contact sites with multiple organelles using SIM. Using C-Py, the subcellular distribution and dynamic processes of LDs in living cells were observed under SIM. The formation of contact sites between LDs and multiple organelles was visualized at a resolution below ~200 nm. The number of LD-mitochondria contact sites formed was decreased by lipopolysaccharide treatment inducing an inflammatory environment. Conclusions: C-Py provides strategies for the design of ultra-highly selective biosensors and a new tool for investigating the role and regulation of LDs in living cells at the nanoscale.
O13-4 Tepotinib safety in MET exon 14 (METex14) skipping NSCLC: Updated results from the VISION trial
Authors: Masahiro Morise, Hiroshi Sakai, Remi Veillon, Xiuning Le, Enriqueta Felip, Marina Chiara Garassino, Alexis B. Cortot, Egbert Smit, Keunchil Park, Frank Griesinger, Christian Britschgi, Yi-Long Wu, Karin Berghoff, Gordon Otto, Rolf Bruns, Paul Paik
Journal: Annals of Oncology (2021)
Human autoinflammatory disease reveals ELF4 as a transcriptional regulator of inflammation
Authors: Paul M. Tyler, Molly L. Bucklin, Mengting Zhao, Timothy J. Maher, Andrew J. Rice, Weizhen Ji, Neil Warner, Jie Pan, Raffaella Morotti, Paul McCarthy, Anne Griffiths, Annemarie M. C. van Rossum, Iris H.I.M. Hollink, Virgil A.S.H. Dalm, Jason Catanzaro, Saquib A. Lakhani, Aleixo M. Muise, Carrie L. Lucas
Journal: Nature Immunology (2021)
<b>Erratum to:</b> Hypertension, the renin–angiotensin system, and the risk of lower respiratory tract infections and lung injury: implications for COVID-19: European Society of Hypertension COVID-19 Task Force Review of Evidence
Authors: Reinhold Kreutz, Engi Abd El-Hady Algharably, Michel Azizi, Piotr Dobrowolski, Tomasz Guzik, Andrzej Januszewicz, Alexandre Persu, Aleksander Prejbisz, Thomas Günther Riemer, Ji-Guang Wang, Michel Burnier
Journal: Cardiovascular Research (2021)

Systemic arterial hypertension (referred to as hypertension herein) is a major risk factor of mortality worldwide, and its importance is further emphasized in the context of the novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection referred to as COVID-19  Patients with severe COVID-19 infections commonly are older and have a history of hypertension  Almost 75% of patients who have died in the pandemic in Italy had hypertension  This raised multiple questions regarding a more severe course of COVID-19 in relation to hypertension itself as well as its treatment with renin-angiotensin system (RAS) blockers, e g  angiotensin-converting enzyme inhibitors (ACEIs) and angiotensin receptor blockers (ARBs)  We provide a critical review on the relationship of hypertension, RAS, and risk of lung injury  We demonstrate lack of sound evidence that hypertension per se is an independent risk factor for COVID-19  Interestingly, ACEIs and ARBs may be associated with lower incidence and/or improved outcome in patients with lower respiratory tract infections  We also review in detail the molecular mechanisms linking the RAS to lung damage and the potential clinical impact of treatment with RAS blockers in patients with COVID-19 and a high cardiovascular and renal risk  This is related to the role of angiotensin-converting enzyme 2 (ACE2) for SARS-CoV-2 entry into cells, and expression of ACE2 in the lung, cardiovascular system, kidney, and other tissues  In summary, a critical review of available evidence does not support a deleterious effect of RAS blockers in COVID-19 infections  Therefore, there is currently no reason to discontinue RAS blockers in stable patients facing the COVID-19 pandemic
Abstract 14878: Baroreflex Failure Induces Striking Volume Intolerance In A Rat Model With Normal Left Ventricular Function
Authors: Kouta Funakoshi, Kazuya Hosokawa, Atsushi Tanaka, Takafumi Sakamoto, Ken Onitsuka, Kazuo Sakamoto, Tomoyuki Tobushi, Takeo Fujino, Keita Saku, Yoshinori Murayama, Tomomi Ide, Kenji Sunagawa
Journal: Circulation (2011)

Background: In patients with heart failure with preserved ejection fraction (HFpEF), minor (intravascular) volume reduction often rapidly resolves pulmonary edema. Major risk factors of HFpEF such ...
Disparities in COVID-19 Vaccination Coverage Among Health Care Personnel Working in Long-Term Care Facilities, by Job Category, National Healthcare Safety Network — United States, March 2021
Authors: James T. Lee, Sandy P. Althomsons, Hsiu Wu, Daniel S. Budnitz, Elizabeth J. Kalayil, Megan C. Lindley, Cassandra Pingali, Carolyn B. Bridges, Andrew I. Geller, Amy Parker Fiebelkorn, Samuel B. Graitcer, James A. Singleton, Suchita A. Patel
Journal: MMWR Morbidity and Mortality Weekly Report (2021)

Residents of long-term care facilities (LTCFs) and health care personnel (HCP) working in these facilities are at high risk for COVID-19-associated mortality.As of March 2021, deaths among LTCF residents and HCP have accounted for almost one third (approximately 182,000) of COVID-19-associated deaths in the United States (1).Accordingly, LTCF residents and HCP were prioritized for early receipt of COVID-19 vaccination and were targeted for on-site vaccination through the federal Pharmacy Partnership for Long-Term Care Program (2).In December 2020, CDC's National Healthcare Safety Network (NHSN) launched COVID-19 vaccination modules, which allow U.S. LTCFs to voluntarily submit weekly facility-level COVID-19 vaccination data.*CDC analyzed data submitted during March 1-April 4, 2021, to describe COVID-19 vaccination coverage among a convenience sample of HCP working in LTCFs, by job category, and compare HCP vaccination coverage rates with social vulnerability metrics of the surrounding community using zip code tabulation area (zip code area) estimates.Through April 4, 2021, a total of 300 LTCFs nationwide, representing approximately 1.8% of LTCFs enrolled in NHSN, reported that 22,825 (56.8%) of 40,212 HCP completed COVID-19 vaccination.† Vaccination coverage was highest among physicians and advanced practice providers (75.1%) and lowest among nurses (56.7%) and aides (45.6%).Among aides (including certified nursing assistants, nurse aides, medication aides, and medication assistants), coverage was lower in facilities located in zip code areas with higher social vulnerability (social and structural factors associated with adverse health outcomes), corresponding to vaccination disparities present in the wider community (3).Additional efforts are needed to improve LTCF immunization policies and practices, build confidence in COVID-19 vaccines, and promote COVID-19 vaccination.CDC and partners have prepared education and training resources to help educate HCP and promote COVID-19 vaccination coverage among LTCF staff members.
Assessment of Prostate Cancer Treatment Among Black and White Patients During the COVID-19 Pandemic
Authors: Adrien N. Bernstein, Ruchika Talwar, Elizabeth Handorf, Kaynaat Syed, John Danella, Serge Ginzburg, Laurence Belkoff, Adam C. Reese, Jeffery Tomaszewski, Edouard Trabulsi, Eric A. Singer, Bruce Jacobs, Alexander Kutikov, Robert Uzzo, Jay D. Raman, Thomas Guzzo, Marc C. Smaldone, Andres Correa
Journal: JAMA Oncology (2021)

Early in the COVID-19 pandemic, racial/ethnic minority communities disproportionately experienced poor outcomes; however, the association of the pandemic with prostate cancer (PCa) care is unknown.
Mobilization of the nonconjugative virulence plasmid from hypervirulent Klebsiella pneumoniae
Authors: Yanping Xu, Jianfeng Zhang, Meng Wang, Meng Liu, Guitian Liu, Hongping Qu, Jialin Liu, Zixin Deng, Jingyong Sun, Hong-Yu Ou, Jieming Qu
Journal: Genome Medicine (2021)

Abstract Background Klebsiella pneumoniae , as a global priority pathogen, is well known for its capability of acquiring mobile genetic elements that carry resistance and/or virulence genes. Its virulence plasmid, previously deemed nonconjugative and restricted within hypervirulent K. pneumoniae (hvKP), has disseminated into classic K. pneumoniae (cKP), particularly carbapenem-resistant K. pneumoniae (CRKP), which poses alarming challenges to public health. However, the mechanism underlying its transfer from hvKP to CRKP is unclear. Methods A total of 28 sequence type (ST) 11 bloodstream infection-causing CRKP strains were collected from Ruijin Hospital in Shanghai, China, and used as recipients in conjugation assays. Transconjugants obtained from conjugation assays were confirmed by Xba I and S1 nuclease pulsed-field gel electrophoresis, PCR detection and/or whole-genome sequencing. The plasmid stability of the transconjugants was evaluated by serial culture. Genetically modified strains and constructed mimic virulence plasmids were employed to investigate the mechanisms underlying mobilization. The level of extracellular polysaccharides was measured by mucoviscosity assays and uronic acid quantification. An in silico analysis of 2608 plasmids derived from 814 completely sequenced K. pneumoniae strains available in GenBank was performed to investigate the distribution of putative helper plasmids and mobilizable virulence plasmids. Results A nonconjugative virulence plasmid was mobilized by the conjugative plasmid belonging to incompatibility group F (IncF) from the hvKP strain into ST11 CRKP strains under low extracellular polysaccharide-producing conditions or by employing intermediate E. coli strains. The virulence plasmid was mobilized via four modes: transfer alone, cotransfer with the conjugative IncF plasmid, hybrid plasmid formation due to two rounds of single-strand exchanges at specific 28-bp fusion sites or homologous recombination. According to the in silico analysis, 31.8% (242) of the putative helper plasmids and 98.8% (84/85) of the virulence plasmids carry the 28-bp fusion site. All virulence plasmids carry the origin of the transfer site. Conclusions The nonconjugative virulence plasmid in ST11 CRKP strains is putatively mobilized from hvKP or E. coli intermediates with the help of conjugative IncF plasmids. Our findings emphasize the importance of raising public awareness of the rapid dissemination of virulence plasmids and the consistent emergence of hypervirulent carbapenem-resistant K. pneumoniae (hv-CRKP) strains.
Distinct Outcome Based on Fusion Transcript in t(16;21) Rearranged Pediatric AML, a Collaborative Retrospective Analysis By the I-BFM SG
Authors: Sanne Noort, Martin Zimmermann, Dirk Reinhardt, Wendy Cuccuini, Pigazzi Martina, Todd A Alonzo, Betsy A Hirsch, Daisuke Tomizawa, Franco Locatelli, Tanja A. Gruber, Susana C. Raimondi, Edwin Sonneveld, Daniel K.L. Cheuk, Michael Dworzak, Jan Stary, Jonas Abrahamsson, Nira Arad-Cohen, Walentyna Balwierz, Barbara De Moerloose, Marry M. Van den Heuvel-Eibrink, C. Michel Zwaan
Journal: Blood (2017)
Pathogen-free diagnosis of tuberculosis
Authors: Jan Heyckendorf, Maja Reimann, Sebastian Marwitz, Christoph Lange, Korkut Avsar, Andrew R. DiNardo, Gunar Günther, Michael Hoelscher, Elmira Ibraim, Barbara Kalsdorf, Stefan H.E. Kaufmann, Irina Kontsevaya, Frank van Leth, Anna M. Mandalakas, Florian Maurer, Marius Müller, Dörte Nitschkowski, Ioana D. Olaru, Cristina Popa, Andrea Rachow, Thierry Rolling, Jan Rybniker, Helmut J.F. Salzer, Patricia Sanchez-Carballo, Maren Schuhmann, Dagmar Schaub, Victor Spinu, Isabelle Suárez, Elena Terhalle, Markus Unnewehr, January Weiner, Torsten Goldmann
Journal: The Lancet Infectious Diseases (2021)
Length and Redundancy of Outpatient Progress Notes Across a Decade at an Academic Medical Center
Authors: Adam Rule, Steven Bedrick, Michael F. Chiang, Michelle R. Hribar
Journal: JAMA Network Open (2021)

<h3>Importance</h3> There is widespread concern that clinical notes have grown longer and less informative over the past decade. Addressing these concerns requires a better understanding of the magnitude, scope, and potential causes of increased note length and redundancy. <h3>Objective</h3> To measure changes between 2009 and 2018 in the length and redundancy of outpatient progress notes across multiple medical specialties and investigate how these measures associate with author experience and method of note entry. <h3>Design, Setting, and Participants</h3> This cross-sectional study was conducted at Oregon Health &amp; Science University, a large academic medical center. Participants included clinicians and staff who wrote outpatient progress notes between 2009 and 2018 for a random sample of 200 000 patients. Statistical analysis was performed from March to August 2020. <h3>Exposures</h3> Use of a comprehensive electronic health record to document patient care. <h3>Main Outcomes and Measures</h3> Note length, note redundancy (ie, the proportion of text identical to the patient’s last note), and percentage of templated, copied, or directly typed note text. <h3>Results</h3> A total of 2 704 800 notes written by 6228 primary authors across 46 specialties were included in this study. Median note length increased 60.1% (99% CI, 46.7%-75.2%) from a median of 401 words (interquartile range [IQR], 225-660 words) in 2009 to 642 words (IQR, 399-1007 words) in 2018. Median note redundancy increased 10.9 percentage points (99% CI, 7.5-14.3 percentage points) from 47.9% in 2009 to 58.8% in 2018. Notes written in 2018 had a mean value of just 29.4% (99% CI, 28.2%-30.7%) directly typed text with the remaining 70.6% of text being templated or copied. Mixed-effect linear models found that notes with higher proportions of templated or copied text were significantly longer and more redundant (eg, in the 2-year model, each 1% increase in the proportion of copied or templated note text was associated with 1.5% [95% CI, 1.5%-1.5%] and 1.6% [95% CI, 1.6%-1.6%] increases in note length, respectively). Residents and fellows also wrote significantly (26.3% [95% CI, 25.8%-26.7%]) longer notes than more senior authors, as did more recent hires (1.8% for each year later [95% CI, 1.3%-2.4%]). <h3>Conclusions and Relevance</h3> In this study, outpatient progress notes grew longer and more redundant over time, potentially limiting their use in patient care. Interventions aimed at reducing outpatient progress note length and redundancy may need to simultaneously address multiple factors such as note template design and training for both new and established clinicians.
Audio Interview: The Impact of Covid-19 on Trainees and Junior Faculty
Authors: Eric J. Rubin, Lindsey R. Baden, Katrina A. Armstrong, Stephen Morrissey
Journal: New England Journal of Medicine (2021)

The Impact of Covid-19 on Trainees and Junior Faculty In this audio interview conducted on July 20, 2021, the editors are joined by Katrina Armstrong, physician-in-chief at Massachusetts General Ho...
A 35-YEAR-OLD WOMAN WITH RECURRENT STROKES, AN INTRACARDIAC LESION, ANEMIA, AND THROMBOCYTOPENIA - ANTIPHOSPHOLIPID-ANTIBODY SYNDROME - ANA-NEGATIVE SYSTEMIC LUPUS-ERYTHEMATOSUS
Authors: Df Giansiracusa, F Staffordbrady, Re Scully, Kj Momose, Me King, Ep Richardson
Journal: New England Journal of Medicine (1988)
Hyporeninemic hypertension
Authors: S. Vaisrub
Journal: JAMA (1973)

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Immunogenicity and safety of the CoronaVac inactivated vaccine in patients with autoimmune rheumatic diseases: a phase 4 trial
Authors: Ana C. Medeiros-Ribeiro, Nadia E. Aikawa, Carla G. S. Saad, Emily F. N. Yuki, Tatiana Pedrosa, Solange R. G. Fusco, Priscila T. Rojo, Rosa M. R. Pereira, Samuel K. Shinjo, Danieli C. O. Andrade, Percival D. Sampaio-Barros, Carolina T. Ribeiro, Giordano B. H. Deveza, Victor A. O. Martins, Clovis A. Silva, Marta H. Lopes, Alberto J. S. Duarte, Leila Antonangelo, Ester C. Sabino, Esper G. Kallas, Sandra G. Pasoto, Eloisa Bonfa
Journal: Nature Medicine (2021)