tbuckley/cabot-search huggingface dataset:
Socioeconomic factors and outcomes from exercise-related sudden cardiac arrest in high school student-athletes in the USA
Authors: Jared Schattenkerk, Kristen Kucera, Danielle F Peterson, Robert A Huggins, Jonathan A Drezner
Journal: British Journal of Sports Medicine (2021)

Minority student-athletes have a lower survival rate from sudden cardiac arrest (SCA) than non-minority student-athletes. This study examined the relationship between high school indicators of socioeconomic status (SES) and survival in student-athletes with exercise-related SCA.High school student-athletes in the USA with exercise-related SCA on school campuses were prospectively identified from 1 July 2014 to 30 June 2018 by the National Center for Catastrophic Sports Injury Research. High school indicators of SES included the following: median household and family income, proportion of students on free/reduced lunch and percent minority students. Resuscitation details included witnessed arrest, presence of an athletic trainer, bystander cardiopulmonary resuscitation and use of an on-site automated external defibrillator (AED). The primary outcome was survival to hospital discharge. Differences in survival were analysed using risk ratios (RR) and univariate general log-binomial regression models.Of 111 cases identified (mean age 15.8 years, 88% male, 49% white non-Hispanic), 75 (68%) survived. Minority student-athletes had a lower survival rate compared with white non-Hispanic student-athletes (51.1% vs 75.9%; RR 0.67, 95% CI 0.49 to 0.92). A non-significant monotonic increase in survival was observed with increasing median household or family income and with decreasing percent minority students or proportion on free/reduced lunch. The survival rate was 83% if an athletic trainer was on-site at the time of SCA and 85% if an on-site AED was used.Minority student-athletes with exercise-related SCA on high school campuses have lower survival rates than white non-Hispanic athletes, but this difference is not fully explained by SES markers of the school.
A broadly cross-reactive antibody neutralizes and protects against sarbecovirus challenge in mice
Authors: David R. Martinez, Alexandra Schäfer, Sophie Gobeil, Dapeng Li, Gabriela De la Cruz, Robert Parks, Xiaozhi Lu, Maggie Barr, Victoria Stalls, Katarzyna Janowska, Esther Beaudoin, Kartik Manne, Katayoun Mansouri, Robert J. Edwards, Kenneth Cronin, Boyd Yount, Kara Anasti, Stephanie A. Montgomery, Juanjie Tang, Hana Golding, Shaunna Shen, Tongqing Zhou, Peter D. Kwong, Barney S. Graham, John R. Mascola, David C. Montefiori, S. Munir Alam, Gregory D. Sempowski, Surender Khurana, Kevin Wiehe, Kevin O. Saunders, Priyamvada Acharya, Barton F. Haynes, Ralph S. Baric
Journal: Science Translational Medicine (2021)

Severe acute respiratory syndrome coronaviruses 1 (SARS-CoV) and 2 (SARS-CoV-2), including SARS-CoV-2 variants of concern, can cause deadly infections. The mortality associated with sarbecovirus infection underscores the importance of developing broadly effective countermeasures against them, which could be key in the prevention and mitigation of current and future zoonotic events. Here, we demonstrate the neutralization of SARS-CoV; bat coronaviruses WIV-1 and RsSHC014; and SARS-CoV-2 variants D614G, B.1.1.7, B.1.351, P.1, B.1.429, B.1.526, B.1.617.1, and B.1.617.2 by a receptor binding domain (RBD)–specific human antibody, DH1047. Prophylactic and therapeutic treatment with DH1047 was protective against SARS-CoV, WIV-1, RsSHC014, and SARS-CoV-2 B.1.351 infection in mice. Binding and structural analysis showed high affinity binding of DH1047 to an epitope that is highly conserved among sarbecoviruses. Thus, DH1047 is a broadly protective antibody that can prevent infection and mitigate outbreaks caused by SARS-related strains and SARS-CoV-2 variants. Our results also suggest that the conserved RBD epitope bound by DH1047 is a rational target for a universal sarbecovirus vaccine.
Comparison of Haematopoietic Stem Cell Transplantation Approaches in Primary Plasma Cell Leukaemia
Authors: Sarah Lawless, Iacobelli Simona, Anja van Biezen, Linda Koster, Patrice Chevallier, Didier Blaise, Roberto Foà, Reza Tabrizi, Nicolaas PM Schaap, Stig Lenhoff, Nigel H. Russell, Xavier Poiré, Eefke Petersen, Jan J. Cornelissen, Paolo Di Bartolomeo, Keith Wilson, Martin Schipperus, Bruno Lioure, William Arcese, Ghulam J Mufti, John A Snowden, Jurgen Finke, Curly Morris, Laurent Garderet, Nicolaus Kröger, Stefan Schönland
Journal: Blood (2016)
Design of CX-3543, a novel multi-targeting antitumor agent
Authors: William G. Rice, John K. C. Lim, Michael K. Schwaebe, Adam Siddiqui-Jain, Nicole H. Streiner, Katharine B. Trent, Jeffrey P. Whitten, Laurence H. Hurley, Daniel D. Von Hoff
Journal: Cancer Research (2005)

2530  Selective targeting of cell signaling pathways has gained favor as a therapeutic strategy, as evidenced by the dramatic successes of molecular-targeting cancer drugs that are now known to act on a cluster of related targets (such as related tyrosine kinase enzymes). In a novel targeted therapeutic approach, a G-quadruplex DNA motif in the promoter regions of many well characterized oncogenes is targeted by a drug-like small molecule, CX-3543, which demonstrates in vivo efficacy in multiple solid tumor xenograft models. The design of CX-3543 utilized a fluoroquinolone core having DNA recognition properties. Medicinal chemistry efforts introduced drug-like moieties to achieve desirable molecular recognition and ADMET properties and to remove undesired activity against bacterial Gyrase and eukaryotic Topoisomerase enzymes. Using customized screening and molecular selectivity assays, CX-3543 was designed and optimized to bind to a parallel-type quadruplex with significant molecular selectivity relative to other types of quadruplex conformations or other forms of DNA. CX-3543 selectively binds to the quadruplex structures that form in the promoter regions of several major oncogenes including VEGF, PDGF-A, HIF-1a, H-Ras, c-Myc and others. CX-3543 displays no significant inhibition of liver CYP450 enzymes, demonstrates metabolic stability with human hepatocytes, and is non-mutagenic in the Ames genotoxicity test. Moreover, CX-3543 displays favorable pharmacokinetic properties in mice, rats and dogs, and is well tolerated in murine xenograft models at doses substantially above those needed to demonstrate an antitumor effect. In in vivo tests, CX-3543 inhibits tumor growth in pancreatic cancer (MiaPaCa), refractory prostate cancer (PC-3), and colorectal cancer (HCT-116) xenograft models. Clinical development is planned to test the safety and efficacy of CX-3543 in cancers with significant unmet medical needs, specifically in tumors driven by relevant oncogenes, including certain lymphomas and colorectal, renal, lung, prostate, ovarian, pancreatic and breast cancers.
Tips and tricks on how to use Twitter
Authors: Daniel Rzewnicki, Nikki Nabavi
Journal: BMJ (2021)

Four expert users at Emory University School of Medicine, Atlanta, Georgia, talk Twitter to Daniel Rzewnicki and give some invaluable advice for those wanting to use this platform in a healthcare environment

Twitter is a common communication tool for individuals, organisations, scientific journals, and learned bodies such as the Royal Colleges,1 and it has been recognised as a useful tool for medical education, networking and connecting with other students or faculty, and a tool for creative writing and reflection.23

BMJ Student spoke to doctors with a following on Twitter (box 1) who share their advice on how to use this social media application effectively.

Box 1 
### Meet the doctors from Emory University School of Medicine, Georgia, Atlanta

#### Kimberly Manning (@gradydoctor)

Kimberly Manning is a professor and associate vice chair of diversity, equity, and inclusion. The Oprah Magazine described her blog as “one of the top four medical blogs you should read.” Manning is active on Twitter and has more than 80 000 followers.

#### Jennifer Spicer (@JenniferSpicer4)

Jennifer Spicer is an assistant professor of medicine in the Division of Infectious Diseases and director of the Distinction in Medical Education for the internal medicine residency programme. She is passionate about curriculum development and instructional methods in medical education.

#### Meredith Greer (@EmmGeezee)

Meredith Greer is a newly appointed assistant professor in pulmonary and critical care and sleep medicine with a clinical interest in neuromuscular pulmonology. She is passionate about medical education and she is a constant source of positivity on Twitter.

#### Caroline Coleman (@cg_coleman)

Caroline Coleman finished medical school at Emory University in May 2020 and stayed on for an internal medicine residency. She is a graphic artist whose illustrations have appeared in board review books, infographics, and visual abstracts.RETURN TO TEXT

If you are new to Twitter or social media, helpful summaries are available to get you started on the basics, such as finding your way around the app or understanding …
Brain injury after cardiac arrest: pathophysiology, treatment, and prognosis
Authors: Claudio Sandroni, Tobias Cronberg, Mypinder Sekhon
Journal: Intensive Care Medicine (2021)

Post-cardiac arrest brain injury (PCABI) is caused by initial ischaemia and subsequent reperfusion of the brain following resuscitation. In those who are admitted to intensive care unit after cardiac arrest, PCABI manifests as coma, and is the main cause of mortality and long-term disability. This review describes the mechanisms of PCABI, its treatment options, its outcomes, and the suggested strategies for outcome prediction.
Amniotic fluid stabilized lipid nanoparticles for in utero intra-amniotic mRNA delivery
Authors: Kelsey L. Swingle, Margaret M. Billingsley, Sourav K. Bose, Brandon White, Rohan Palanki, Apeksha Dave, Savan K. Patel, Ningqiang Gong, Alex G. Hamilton, Mohamad-Gabriel Alameh, Drew Weissman, William H. Peranteau, Michael J. Mitchell
Journal: Journal of Controlled Release (2021)
Humoral immunogenicity of the seasonal influenza vaccine before and after CAR-T-cell therapy: a prospective observational study
Authors: Carla S Walti, Andrea N Loes, Kiel Shuey, Elizabeth M Krantz, Jim Boonyaratanakornkit, Jacob Keane-Candib, Tillie Loeffelholz, Caitlin R Wolf, Justin J Taylor, Rebecca A Gardner, Damian J Green, Andrew J Cowan, David G Maloney, Cameron J Turtle, Steven A Pergam, Helen Y Chu, Jesse D Bloom, Joshua A Hill
Journal: Journal for ImmunoTherapy of Cancer (2021)

Recipients of chimeric antigen receptor-modified T (CAR-T) cell therapies for B cell malignancies have profound and prolonged immunodeficiencies and are at risk for serious infections, including respiratory virus infections. Vaccination may be important for infection prevention, but there are limited data on vaccine immunogenicity in this population. We conducted a prospective observational study of the humoral immunogenicity of commercially available 2019–2020 inactivated influenza vaccines in adults immediately prior to or while in durable remission after CD19-, CD20-, or B cell maturation antigen-targeted CAR-T-cell therapy, as well as controls. We tested for antibodies to all four vaccine strains using neutralization and hemagglutination inhibition (HAI) assays. Antibody responses were defined as at least fourfold titer increases from baseline. Seroprotection was defined as a HAI titer ≥40. Enrolled CAR-T-cell recipients were vaccinated 14–29 days prior to (n=5) or 13–57 months following therapy (n=13), and the majority had hypogammaglobulinemia and cellular immunodeficiencies prevaccination. Eight non-immunocompromised adults served as controls. Antibody responses to ≥1 vaccine strain occurred in 2 (40%) individuals before CAR-T-cell therapy and in 4 (31%) individuals vaccinated after CAR-T-cell therapy. An additional 1 (20%) and 6 (46%) individuals had at least twofold increases, respectively. One individual vaccinated prior to CAR-T-cell therapy maintained a response for &gt;3 months following therapy. Across all tested vaccine strains, seroprotection was less frequent in CAR-T-cell recipients than in controls. There was evidence of immunogenicity even among individuals with low immunoglobulin, CD19 + B cell, and CD4 + T-cell counts. These data support consideration for vaccination before and after CAR-T-cell therapy for influenza and other relevant pathogens such as SARS-CoV-2, irrespective of hypogammaglobulinemia or B cell aplasia. However, relatively impaired humoral vaccine immunogenicity indicates the need for additional infection-prevention strategies. Larger studies are needed to refine our understanding of potential correlates of vaccine immunogenicity, and durability of immune responses, in CAR-T-cell therapy recipients.
Reconciling Supported Decision Making with Shared Decision Making in the Context of Potential Vulnerability
Authors: Devora Shapiro, Lauren R. Sankary, Paul J. Ford
Journal: The American Journal of Bioethics (2021)

Supported decision making, as outlined by Peterson et al. highlights real-world challenges in the messy context of clinical care (Peterson et al. 2021). We agree with Peterson et al. that patients ...
In situ delivery of apoptotic bodies derived from mesenchymal stem cells via a hyaluronic acid hydrogel: A therapy for intrauterine adhesions
Authors: Liaobing Xin, Cheng Wei, Xiaomei Tong, Yangyang Dai, Dong Huang, Jianmin Chen, Lie Ma, Songying Zhang
Journal: Bioactive Materials (2021)

Stem cell-based and stem cell-derived exosome-based therapies have shown promising potential for endometrial regeneration and the clinical treatment of intrauterine adhesions (IUAs). Evidence shows that apoptosis occurs in a majority of grafted stem cells, and apoptotic bodies (ABs) play a critical role in compensatory tissue regeneration. However, the therapeutic potential of AB-based therapy and its mechanism have not been explored in detail. Here, a cell-free therapeutic strategy was developed by incorporating mesenchymal stem cell-derived ABs into a hyaluronic acid (HA) hydrogel to achieve endometrial regeneration and fertility restoration. Specifically, we found that the ABs could induce macrophage immunomodulation, cell proliferation, and angiogenesis in vitro. The HA hydrogel promoted the retention of ABs and facilitated their continuous release. In a murine model of acute endometrial damage and a rat model of IUAs, in situ injection of the AB-laden HA hydrogel could efficiently reduce fibrosis and promote endometrial regeneration, resulting in the fertility restoration. Consequently, ABs show good potential as therapeutic vesicles, and the AB-laden HA hydrogel appears to be a clinically feasible and cell-free alternative for endometrial regeneration and IUA treatment.
Fungal lysozyme leverages the gut microbiota to curb DSS-induced colitis
Authors: Ida Søgaard Larsen, Benjamin A. H. Jensen, Erica Bonazzi, Béatrice S. Y. Choi, Nanna Ny Kristensen, Esben Gjerløff Wedebye Schmidt, Annika Süenderhauf, Laurence Morin, Peter Bjarke Olsen, Lea Benedicte Skov Hansen, Torsten Schröder, Christian Sina, Benoît Chassaing, André Marette
Journal: Gut Microbes (2021)

Colitis is characterized by colonic inflammation and impaired gut health. Both features aggravate obesity and insulin resistance. Host defense peptides (HDPs) are key regulators of gut homeostasis and generally malfunctioning in above-mentioned conditions. We aimed here to improve bowel function in diet-induced obesity and chemically induced colitis through daily oral administration of lysozyme, a well-characterized HDP, derived from Acremonium alcalophilum.C57BL6/J mice were fed either low-fat reference diet or HFD ± daily gavage of lysozyme for 12 weeks, followed by metabolic assessment and evaluation of colonic microbiota encroachment. To further evaluate the efficacy of intestinal inflammation, we next supplemented chow-fed BALB/c mice with lysozyme during Dextran Sulfate Sodium (DSS)-induced colitis in either conventional or microbiota-depleted mice. We assessed longitudinal microbiome alterations by 16S amplicon sequencing in both models.Lysozyme dose-dependently alleviated intestinal inflammation in DSS-challenged mice and further protected against HFD-induced microbiota encroachment and fasting hyperinsulinemia. Observed improvements of intestinal health relied on a complex gut flora, with the observation that microbiota depletion abrogated lysozyme's capacity to mitigate DSS-induced colitis.Akkermansia muciniphila associated with impaired gut health in both models, a trajectory that was mitigated by lysozyme administration. In agreement with this notion, PICRUSt2 analysis revealed specific pathways consistently affected by lysozyme administration, independent of vivarium, disease model and mouse strain.Taking together, lysozyme leveraged the gut microbiota to curb DSS-induced inflammation, alleviated HFD-induced gastrointestinal disturbances and lowered fasting insulin levels in obese mice. Collectively, these data present A. alcalophilum-derived lysozyme as a promising candidate to enhance gut health.
Community transmission and viral load kinetics of the SARS-CoV-2 delta (B.1.617.2) variant in vaccinated and unvaccinated individuals in the UK: a prospective, longitudinal, cohort study
Authors: Anika Singanayagam, Seran Hakki, Jake Dunning, Kieran J Madon, Michael A Crone, Aleksandra Koycheva, Nieves Derqui-Fernandez, Jack L Barnett, Michael G Whitfield, Robert Varro, Andre Charlett, Rhia Kundu, Joe Fenn, Jessica Cutajar, Valerie Quinn, Emily Conibear, Wendy Barclay, Paul S Freemont, Graham P Taylor, Shazaad Ahmad, Maria Zambon, Neil M Ferguson, Ajit Lalvani, Anjna Badhan, Simon Dustan, Chitra Tejpal, Anjeli V Ketkar, Janakan Sam Narean, Sarah Hammett, Eimear McDermott, Timesh Pillay, Hamish Houston, Constanta Luca, Jada Samuel, Samuel Bremang, Samuel Evetts, John Poh, Charlotte Anderson, David Jackson, Shahjahan Miah, Joanna Ellis, Angie Lackenby
Journal: The Lancet Infectious Diseases (2021)
TCT-178 Clinical Outcomes in Troponin-Negative Patients Treated With Short DAPT Undergoing Percutaneous Coronary Intervention: A Subanalysis of the ReCre8 Trial
Authors: Nicole van Hemert, Michiel Voskuil, Rik Rozemeijer, Adriaan Kraaijeveld, Saskia Rittersma, Geert Leenders, Mera Stein, Peter Frambach, Pim van der Harst, Pierfrancesco Agostoni, Pieter Stella
Journal: Journal of the American College of Cardiology (2021)
Benchmarking off-the-shelf statistical shape modeling tools in clinical applications
Authors: Anupama Goparaju, Krithika Iyer, Alexandre Bône, Nan Hu, Heath B. Henninger, Andrew E. Anderson, Stanley Durrleman, Matthijs Jacxsens, Alan Morris, Ibolya Csecs, Nassir Marrouche, Shireen Y. Elhabian
Journal: Medical Image Analysis (2021)
TCT-185 Change in Left Ventricular Diastolic Dysfunction After Transcatheter Aortic Valve Replacement and Outcomes in Patients With Severe Aortic Stenosis
Authors: Ali Malik, David Cohen, John Spertus, John Saxon, Philippe Pibarot, Rebecca Hahn, Maria Alu, Kan Shang, Erin Rogers, Susheel Kodali, Vinod Thourani, Michael Mack, Adnan Chhatriwalla
Journal: Journal of the American College of Cardiology (2021)
Rome declaration: G20 leaders fail to make specific commitments to limit temperature rises
Authors: Jacqui Wise
Journal: BMJ (2021)

World leaders meeting at the G20 summit in Rome agreed that countries must take “meaningful and effective actions” to limit global average temperature increase to 1.5°C above pre-industrial levels but failed to make any specific commitments to meet that target.

The final G20 leaders’ declaration said that they will accelerate actions to achieving global net zero greenhouse gas emissions or carbon neutrality “by or around mid-century” but did not include a commitment to net zero by 2050. They did however acknowledge the science on the need to act faster and committed to take further action …
Editor's Note: Castration Therapy Results in Decreased Ku70 Levels in Prostate Cancer
Authors: Firas L.T. Al-Ubaidi, Niklas Schultz, Olga Loseva, Lars Egevad, Torvald Granfors, Thomas Helleday
Journal: Clinical Cancer Research (2021)

The editors are publishing this note to alert readers to a concern about this article (1): in Fig. 2A, the last two enlarged insets shown beneath the main image were unintentionally duplicated. The middle inset is correct.
Therapeutic targeting of inflammation in hypertension: from novel mechanisms to translational perspective
Authors: E C Murray, R Nosalski, N MacRitchie, M Tomaszewski, P Maffia, D G Harrison, T J Guzik
Journal: Cardiovascular Research (2021)

Both animal models and human observational and genetic studies have shown that immune and inflammatory mechanisms play a key role in hypertension and its complications. We review the effects of immunomodulatory interventions on blood pressure, target organ damage, and cardiovascular risk in humans. In experimental and small clinical studies, both non-specific immunomodulatory approaches, such as mycophenolate mofetil and methotrexate, and medications targeting T and B lymphocytes, such as tacrolimus, cyclosporine, everolimus, and rituximab, lower blood pressure and reduce organ damage. Mechanistically targeted immune interventions include isolevuglandin scavengers to prevent neo-antigen formation, co-stimulation blockade (abatacept, belatacept), and anti-cytokine therapies (e.g. secukinumab, tocilizumab, canakinumab, TNF-α inhibitors). In many studies, trial designs have been complicated by a lack of blood pressure-related endpoints, inclusion of largely normotensive study populations, polypharmacy, and established comorbidities. Among a wide range of interventions reviewed, TNF-α inhibitors have provided the most robust evidence of blood pressure lowering. Treatment of periodontitis also appears to deliver non-pharmacological anti-hypertensive effects. Evidence of immunomodulatory drugs influencing hypertension-mediated organ damage are also discussed. The reviewed animal models, observational studies, and trial data in humans, support the therapeutic potential of immune-targeted therapies in blood pressure lowering and in hypertension-mediated organ damage. Targeted studies are now needed to address their effects on blood pressure in hypertensive individuals.
Local Delivery of Senolytic Drug Inhibits Intervertebral Disc Degeneration and Restores Intervertebral Disc Structure
Authors: Songhyun Lim, Seong Bae An, Mungyo Jung, Hari Prasad Joshi, Hemant Kumar, Cheesue Kim, Seuk Young Song, Ju‐Ro Lee, Mikyung Kang, Inbo Han, Byung‐Soo Kim
Journal: Advanced Healthcare Materials (2021)

Intervertebral disc (IVD) degeneration (IVDD) is a leading cause of chronic low back pain. There is a strong clinical demand for more effective treatments for IVDD as conventional treatments provide only symptomatic relief rather than arresting IVDD progression. This study shows that senolytic therapy with local drug delivery can inhibit IVDD and restore IVD integrity. ABT263, a senolytic drug, is loaded in poly(lactic-co-glycolic acid) nanoparticles (PLGA-ABT) and intradiscally administered into injury-induced IVDD rat models. The single intradiscal injection of PLGA-ABT may enable local delivery of the drug to avascular IVD, prevention of potential systemic toxicity caused by systemic administration of senolytic drug, and morbidity caused by repetitive injections of free drug into the IVD. The strategy results in the selective elimination of senescent cells from the degenerative IVD, reduces expressions of pro-inflammatory cytokines and matrix proteases in the IVD, inhibits progression of IVDD, and even restores the IVD structure. This study demonstrates for the first time that local delivery of senolytic drug can effectively treat senescence-associated IVDD. This approach can be extended to treat other types of senescence-associated degenerative diseases.
TCT-411 Prognostic Implications of the HFA-PEFF Score in Patients With Preserved Ejection Fraction After Transcatheter Aortic Valve Replacement
Authors: Hatim Seoudy, Mira von Eberstein, Johanne Frank, Maren Thomann, Thomas Puehler, Georg Lutter, Matthias Lutz, Peter Bramlage, Norbert Frey, Mohammed Saad, Derk Frank
Journal: Journal of the American College of Cardiology (2021)