tbuckley/cabot-search huggingface dataset:
Implementation and Evolution of Mitigation Measures, Testing, and Contact Tracing in the National Football League, August 9–November 21, 2020
Authors: Christina D. Mack, Erin B. Wasserman, Cria G. Perrine, Adam MacNeil, Deverick J. Anderson, Emily Myers, Sabrina Smith, L. Clifford McDonald, Michael Osterholm, Gary S. Solomon, Thom Mayer, Allen Sills, Dawn Aponte, Michele Best, Paul Blalock, Meghan C. Carroll, M. Anthony Casolaro, Molly Delaney, Daniel Eichner, Larry Ferazani, Jacob Frank, Christopher J. Hostler, Tiffany Koch, John Lynch, Jimmie Mancell, Damion Martins, John Mellody, Jeff Miller, Navdeep Singh, Eric Sugarman, Leah Triola, Patti Walton
Journal: MMWR Morbidity and Mortality Weekly Report (2021)

the 2020 football season in July, implementing extensive mitigation and surveillance measures in facilities and during travel and gameplay.Mitigation protocols* were evaluated and modified based on data from routine reverse transcription-polymerase chain reaction (RT-PCR) tests for SARS-CoV-2, the virus that causes coronavirus 2019 (COVID-19); proximity tracking devices; and detailed interviews.Midseason, transmission was observed in persons who had cumulative interactions of <15 minutes' duration, leading to a revised definition of highrisk contacts that required consideration of mask use, setting and room ventilation in addition to proximity and duration of interaction.The NFL also developed an intensive protocol that imposed stricter infection prevention precautions when a case was identified at an NFL club.The intensive protocol effectively prevented the occurrence of high-risk interactions, with no high-risk contacts identified for 71% of traced cases at clubs under the intensive protocol.The incorporation of the nature and location of the interaction, including mask use, indoor versus outdoor setting, and ventilation, in addition to proximity and duration, likely improved identification of exposed persons at higher risk for SARS-CoV-2 infection.Quarantine of these persons, along with testing and intensive protocols, can reduce spread of infection.The NFL consists of 32 member clubs based in 24 states.The NFL-NFLPA implemented a standard COVID-19 mitigation protocol in July that included mandatory masking; physical distancing; frequent handwashing; facility disinfection; restricted facility access; and regular, frequent testing of players and staff members (1).Contact tracing was performed by trained staff members and supported by KINEXON wearable proximity devices (https://kinexon.com)that were required to be worn by players and personnel when in club environments (2).Device recordings captured consecutive and cumulative minutes/seconds of interactions among persons within 1.8 meters (6 feet) of one another.When testing identified a new COVID-19 case, trained staff members conducted interviews to identify contacts
The Global Landscape of Treatment Standards for Breast Cancer
Authors: Dario Trapani, Jean Yves Douillard, Eric P Winer, Harold Burstein, Lisa Anne Carey, Javier Cortes, Gilberto Lopes, Julie R Gralow, William J Gradishar, Nicola Magrini, Giuseppe Curigliano, Andrè M Ilbawi
Journal: JNCI Journal of the National Cancer Institute (2021)

Breast cancer (BC) is a leading cause of morbidity, mortality, and disability for women worldwide. There is substantial variation in treatment outcomes, which is function of multiple variables, including access to treatment. Treatment standards can promote quality and improve survival; thus, their development should be a priority for the cancer-control planning.We extracted the guidelines for the treatment of BC from a systematic review of the literature. We evaluated the development process, the methodology, and the recommendations formulated and surveyed the country resource stratification. Metrics of health-system capacity were selected to study the guidelines context appropriateness.We analyzed 49 distinct guidelines for BC, mostly in English language (n = 23), developed in upper-middle and high-income countries of the European and American regions (n = 39). A resource-stratified approach was identified in a quarter of the guidelines (n = 11), mostly from resource-constrained settings. Only one-half of the guidelines reached a gender balance of the authorship, and 10.2% were based on a multidisciplinary steering committee. A number of efforts and solutions of resource adaptations were recognized, mostly in low- and middle-income countries. Overall, the national guidelines appeared not sensitive enough of the local health-system capacity in formulating recommendations, with possible exception for the radiation therapy availability.This global landscape of treatment standards for BC demonstrates that the majority is not context appropriate. Research on the formulation of cancer treatment standards is highly warranted, along with novel platforms for developing and disseminating resource-appropriate guidance.
Hand eczema in children referred for patch testing: North American Contact Dermatitis Group Data, 2000–2016*
Authors: J.I. Silverberg, E.M. Warshaw, H.I. Maibach, J.G. DeKoven, J.S. Taylor, A.R. Atwater, D. Sasseville, K.A. Zug, M.J. Reeder, J.F. Fowler, M.D. Pratt, A.F. Fransway, M.J. Zirwas, D.V. Belsito, J.G. Marks, V.A. DeLeo
Journal: British Journal of Dermatology (2021)

Background Little is known about the aetiologies and relevant allergens in paediatric patients with hand eczema (HE). Objectives To characterize the aetiologies and determine the proportion of positive and currently relevant allergens in children/adolescents (age < 18 years) with HE referred for patch testing. Methods A retrospective analysis (2000–2016) of North American Contact Dermatitis Group data was performed. Results Of 1634 paediatric patients, 237 (14·5%) had involvement of the hands. Final physician diagnoses included allergic contact dermatitis (49·4%), atopic dermatitis (37·1%) and irritant contact dermatitis (16·9%). In multivariable logistic regression models, employment was the only association with increased odds of any HE or primary HE. Children with HE vs. those without HE had similar proportions of positive patch tests (56·1% vs. 61·7%; χ2-test, P = 0·11). The five most common currently relevant allergens were nickel, methylisothiazolinone, propylene glycol, decyl glucoside and lanolin. In multivariable logistic regression models of the top 20 relevant allergens, HE was associated with significantly higher odds of currently relevant reactions to lanolin, quaternium-15, Compositae mix, thiuram mix, 2-mercaptobenzathiazole and colophony. The allergens with the highest mean significance-prevalence index number were methylisothiazolinone, carba mix, thiuram mix, nickel and methylchloroisothiazolinone/methylisothiazolinone. Conclusions Children with HE who were referred for patch testing had a high proportion of positive patch tests, which was similar to the proportion found in children without HE. Children with HE had a distinct and fairly narrow profile of currently relevant allergens.
Therapeutic targeting of argininosuccinate synthase 1 (ASS1)-deficient pulmonary fibrosis
Authors: Ji-Min Li, David C. Yang, Justin Oldham, Angela Linderholm, Jun Zhang, Jun Liu, Nicholas J. Kenyon, Ching-Hsien Chen
Journal: Molecular Therapy (2021)

Argininosuccinate synthase 1 (ASS1) serves as a critical enzyme in arginine biosynthesis; however, its role in interstitial lung diseases, particularly idiopathic pulmonary fibrosis (IPF), remains largely unknown. This study aims at characterization and targeting of ASS1 deficiency in pulmonary fibrosis. We find that ASS1 was significantly decreased and inversely correlated with fibrotic status. Transcriptional downregulation of ASS1 was noted in fibroblastic foci of primary lung fibroblasts isolated from IPF patients. Genetic manipulations of ASS1 studies confirm that ASS1 expression inhibited fibroblast cell proliferation, migration, and invasion. We further show that the hepatocyte growth factor receptor (Met) receptor was activated and acted upstream of the Src-STAT3 axis signaling in ASS1-knockdown fibroblasts. Interestingly, both arginine-free conditions and arginine deiminase treatment were demonstrated to kill fibrotic fibroblasts, attenuated bleomycin-induced pulmonary fibrosis in mice, as well as synergistically increased nintedanib efficacy. Our data suggest ASS1 deficiency as a druggable target and also provide a unique therapeutic strategy against pulmonary fibrosis. Argininosuccinate synthase 1 (ASS1) serves as a critical enzyme in arginine biosynthesis; however, its role in interstitial lung diseases, particularly idiopathic pulmonary fibrosis (IPF), remains largely unknown. This study aims at characterization and targeting of ASS1 deficiency in pulmonary fibrosis. We find that ASS1 was significantly decreased and inversely correlated with fibrotic status. Transcriptional downregulation of ASS1 was noted in fibroblastic foci of primary lung fibroblasts isolated from IPF patients. Genetic manipulations of ASS1 studies confirm that ASS1 expression inhibited fibroblast cell proliferation, migration, and invasion. We further show that the hepatocyte growth factor receptor (Met) receptor was activated and acted upstream of the Src-STAT3 axis signaling in ASS1-knockdown fibroblasts. Interestingly, both arginine-free conditions and arginine deiminase treatment were demonstrated to kill fibrotic fibroblasts, attenuated bleomycin-induced pulmonary fibrosis in mice, as well as synergistically increased nintedanib efficacy. Our data suggest ASS1 deficiency as a druggable target and also provide a unique therapeutic strategy against pulmonary fibrosis.
Hematologic disorder–associated <i>Cxcr4</i> gain-of-function mutation leads to uncontrolled extrafollicular immune response
Authors: Nagham Alouche, Amélie Bonaud, Vincent Rondeau, Rim Hussein-Agha, Julie Nguyen, Valeria Bisio, Mélanie Khamyath, Etienne Crickx, Niclas Setterblad, Nicolas Dulphy, Matthieu Mahevas, David H. McDermott, Philip M. Murphy, Karl Balabanian, Marion Espéli
Journal: Blood (2021)
Relationship and improvement strategies between drug nanocarrier characteristics and hemocompatibility: What can we learn from the literature
Authors: Shiqi Guo, Yanan Shi, Yanzi Liang, Lanze Liu, Kaoxiang Sun, Youxin Li
Journal: Asian Journal of Pharmaceutical Sciences (2021)

This article discusses the various blood interactions that may occur with various types of nano drug-loading systems. Nanoparticles enter the blood circulation as foreign objects. On the one hand, they may cause a series of inflammatory reactions and immune reactions, resulting in the rapid elimination of immune cells and the reticuloendothelial system, affecting their durability in the blood circulation. On the other hand, the premise of the drug-carrying system to play a therapeutic role depends on whether they cause coagulation and platelet activation, the absence of hemolysis and the elimination of immune cells. For different forms of nano drug-carrying systems, we can find the characteristics, elements and coping strategies of adverse blood reactions that we can find in previous researches. These adverse reactions may include destruction of blood cells, abnormal coagulation system, abnormal effects of plasma proteins, abnormal blood cell behavior, adverse immune and inflammatory reactions, and excessive vascular stimulation. In order to provide help for future research and formulation work on the blood compatibility of nano drug carriers.
Glomerular Exostosin Deposits in Membranous Lupus Nephritis—a Dialogue
Authors: Marc Hilhorst, Hans-Joachim Anders
Journal: Journal of the American Society of Nephrology (2021)

Membranous nephropathy (MN) is a paradigmatic disease entity that combines severe proteinuria with a classic histopathologic and ultrastructural lesion pattern. Traditionally, MN has been divided into primary (idiopathic) and secondary forms. Among the latter, chronic infections and systemic lupus
Clinical characteristics and outcomes of COVID-19 in haematopoietic stem-cell transplantation recipients: an observational cohort study
Authors: Akshay Sharma, Neel S Bhatt, Andrew St Martin, Muhammad Bilal Abid, Jenni Bloomquist, Roy F Chemaly, Christopher Dandoy, Jordan Gauthier, Lohith Gowda, Miguel-Angel Perales, Stuart Seropian, Bronwen E Shaw, Eileen E Tuschl, Amer M Zeidan, Marcie L Riches, Gunjan L Shah
Journal: The Lancet Haematology (2021)
Neoadjuvant Chemotherapy, Endocrine Therapy, and Targeted Therapy for Breast Cancer: ASCO Guideline
Authors: Larissa A. Korde, Mark R. Somerfield, Lisa A. Carey, Jennie R. Crews, Neelima Denduluri, E. Shelley Hwang, Seema A. Khan, Sibylle Loibl, Elizabeth A. Morris, Alejandra Perez, Meredith M. Regan, Patricia A. Spears, Preeti K. Sudheendra, W. Fraser Symmans, Rachel L. Yung, Brittany E. Harvey, Dawn L. Hershman
Journal: Journal of Clinical Oncology (2021)

To develop guideline recommendations concerning optimal neoadjuvant therapy for breast cancer.
THU0089 Inhibition of rheumatoid arthrirtis synoviocytes growth by taurine chloramine
Authors: E Kontny, J Kowalczewski, I Janicka, M Kurowska, J Marcinkiewicz, W Maslinski
Journal: Annals of the Rheumatic Diseases (2001)

<h3>Background</h3> Hyperplasia of synovial membrane, a characteristic feature of rheumatoid arthritis (RA), is proposed to result from either the enhanced proliferation of fibroblast-like synoviocytes (FLS) or the resistance of these cells to apoptotic death. Therapeutic approaches to inhibit an excessive growth of RA FLS are not satisfactory. We have previously shown that taurine chloramine (Tau-Cl), a chlorinated derivative of a dominant free amino acid taurine (Tau), formed by neutrophils during respiratory burst, inhibits FGF-triggered proliferation of RA FLS (Arthritis Rheum 1999;42:2552). <h3>Objectives</h3> The aim of present study was to investigate the mechanism of Tau-Cl inhibition of RA FLS growth. <h3>Methods</h3> FLS, isolated from the synovial membrane of RA patients, were stimulated <i>in vitro</i> for 18–72 h with 10 ng/ml of either rhPDGF or rhTNF-α. Tau or Tau-Cl were added (at 100–500 μM concentration) together with the stimuli. Cell proliferation was determined by incorporation of 3H-TdR. To evaluate the cytotoxicity of tested compounds, and to estimate the recovery of the cells from the cultures, the lactate dehydrogenase (LDH) activity was measured in culture supernatants and in cell lysates, respectively. The expression of proteins regulating the cell-cycle progression or apoptosis, was estimated by Western bloting. <h3>Results</h3> The rate of spontaneous proliferation of FLS ranged from 176 to 4639 cpm. Both, PDGF and TNF-α raised it significantly by 6 and 2 times, respectively. Tau was neither cytotoxic nor affected the recovery/proliferation of RA FLS. In contrast, Tau-Cl inhibited both the proliferation and the cell recovery in a dose-dependent manner. Independent of the type of stimulus, both responses were reduced by 70% in the presence of 250 μM, and were almost completely blocked (by 90%) in the presence of 500 μM concentration of Tau-Cl. At the same concentrations (250 and 500 μM) Tau-Cl inhibited PDGF- and TNF-α -triggered expression of PCNA (proliferating cell nuclear antigen) but has no effect on the expression of either the Cdk-4 (the cyclin-dependent kinase-4), Cdk-inhibitors (p16, p21, p27) or the anti-apoptotic, Bcl-2, protein. At the late time points (48–72 hrs) only the higher (500 μM) concentration of Tau-Cl exerted cytotoxic (50%) effect. <h3>Conclusion</h3> We report that Tau-Cl, a physiologic factor originated from activated neutrophils, blocks proliferation of RA FLS by affecting the common event critical for the cell cycle progression: the expression of PCNA protein, known to act as a cofactor for DNA polimerase δ. Thus, Tau-Cl might be promising therapeutic agent for RA. Whether Tau-Cl triggers apoptosis of RA FLS is under investigation.
Low-Risk Essential Thrombocythemia: A Comprehensive Review
Authors: Andrew J. Robinson, Anna L. Godfrey
Journal: HemaSphere (2021)

Essential thrombocythemia (ET) is a chronic myeloproliferative neoplasm characterized by a persistently elevated platelet count in the absence of a secondary cause. The clinical consequences of uncontrolled thrombocytosis can include both thrombosis and hemorrhage. Patients with features conferring a “high risk” of vascular events benefit from reduction of the platelet count through cytoreductive therapy. The management of patients who lack such high-risk features has until recently been less well defined, but it is now apparent that many require minimal or even no intervention. In this review, we discuss the diagnostic pathway for younger patients with unexplained thrombocytosis, including screening molecular investigations, the role of bone marrow biopsy, and investigations in those patients negative for the classic myeloproliferative neoplasm driver mutations ( JAK2 , CALR , MPL ). We discuss conventional and novel risk stratification methods in essential thrombocythemia and how these can be best applied in clinical practice, particularly in the era of more comprehensive genomic testing. The treatment approach for “low risk” patients is discussed including antiplatelets and the options for cytoreductive therapy, if indicated, together with areas of clinical need for future study.
Abstract 16263: High Precision Acute Haemodynamic Evaluation of Personalisation of Endocardial Left Ventricular Pacing Site in Patients With Heart Failure
Authors: Charles Butcher, Sayed Sohaib, Matthew Shun-Shin, Ross Haynes, Habib Khan, Andreas Kyriacou, Rui Shi, Emily Cantor, Zhong Chen, Sandeep Panikker, Shouvik Haldar, John Cleland, Hussain Wajid, Vias Markides, David Jones, Rebecca E Lane, Zachary I Whinnett, Mark Mason, Darrel Francis, Tom Wong
Journal: Circulation (2019)

Introduction: In patients with a broad QRS and heart failure, the effects on acute systolic blood pressure (SBP) augmentation during biventricular pacing (BVP) when pacing at different LV endocardi...
When will it be better? Lenvatinib combined with TACE for unresectable hepatocellular carcinoma: A retrospective analysis of real-world evidence in China.
Authors: Lan Zhang, Yanhong Wang, Ningling Ge, Yu-Hong Gan, ZhengGang Ren, Yi Chen
Journal: Journal of Clinical Oncology (2021)

281 Background: TACE and lenvatinib has each shown to prolong overall survival in patients with unresectable HCC, combination of which may also improve clinical outcomes and have been widely used in the real world accordingly. However, the optimal timing of adding on lenvatinb to TACE remains unclear. We are aiming to evaluate the efficacy and safety between two combination strategies. Methods: From Nov 2018 to Jun 2020, 79 consecutive patients had received a combination treatment of lenvatinib and TACE. Patients followed up for more than 2 months were included in this analysis. They were classified as early-combination group(add on lenvatinib before or after the first TACE ) and late-combination group(add on lenvatinib after at least two procedures of TACE ). Tumor response and progression-free survival (PFS,time from the first day of prescribing lenvatinib to progression or death) were assessed according to RECIST1.1 criteria. Liver function were also evaluated at baseline and every 2 months later. AEs were recorded during the combination treatment period according to CTCAE 5.0. Results: A total of 48 u-HCC patients was finally enrolled. Median follow-up in all patients was 9.3(5.3-14.3)months. Patients’ baseline characteristics were similar in two groups. For early-combination group(n=22)and late-combination group(n=26), the mean age was 65±9.7 and 61±11.6years(p=0.2);BCLC stage C HCC was 59% and 54%(p=0.89);and Child-Pugh A proportion was 81.8% and 77%(p=0.73) respectively. The objective response rate(ORR) was 22.9% in total 48 cases. There was no significant difference in response rate (18.2% vs 26.9%, P=0.51) or disease control rate (90.9% vs 92.3%, P=1.00). Median PFS was significantly longer in the early-combination group than that in late-combination group (14.5 vs 8.9 months; p=0.048). The safety profile was similar between two groups. Grade 3/4 adverse events were 3 (13.6%) and 2 cases(7.7%) respectively (P=0.65). Conclusions: This is to date the first real-world data of the combination timing of lenvatinib with TACE in u-HCC patients. Early-combination strategy may be a better option for the u-HCC patients with a longer mPFS.
Liposome induction of CD8+ T cell responses depends on CD169+ macrophages and Batf3-dependent dendritic cells and is enhanced by GM3 inclusion
Authors: J. Grabowska, A.J. Affandi, D. van Dinther, M.K. Nijen Twilhaar, K. Olesek, L. Hoogterp, M. Ambrosini, D.A.M. Heijnen, L. Klaase, A. Hidalgo, K. Asano, P.R. Crocker, G. Storm, Y. van Kooyk, J.M.M. den Haan
Journal: Journal of Controlled Release (2021)

Cancer vaccines aim to efficiently prime cytotoxic CD8+ T cell responses which can be achieved by vaccine targeting to dendritic cells. CD169+ macrophages have been shown to transfer antigen to dendritic cells and could act as an alternative target for cancer vaccines. Here, we evaluated liposomes containing the CD169/Siglec-1 binding ligand, ganglioside GM3, and the non-binding ligand, ganglioside GM1, for their capacity to target antigens to CD169+ macrophages and to induce immune responses. CD169+ macrophages demonstrated specific uptake of GM3 liposomes in vitro and in vivo that was dependent on a functional CD169 receptor. Robust antigen-specific CD8+ and CD4+ T and B cell responses were observed upon intravenous administration of GM3 liposomes containing the model antigen ovalbumin in the presence of adjuvant. Immunization of B16-OVA tumor bearing mice with all liposomes resulted in delayed tumor growth and improved survival. The absence of CD169+ macrophages, functional CD169 molecules, and cross-presenting Batf3-dependent dendritic cells (cDC1s) significantly impaired CD8+ T cell responses, while B cell responses were less affected. In conclusion, we demonstrate that inclusion of GM3 in liposomes enhance immune responses and that splenic CD169+ macrophages and cDC1s are required for induction of CD8+ T cell immunity after liposomal vaccination.
A novel CD4+ CTL subtype characterized by chemotaxis and inflammation is involved in the pathogenesis of Graves’ orbitopathy
Authors: Yue Wang, Ziyi Chen, Tingjie Wang, Hui Guo, Yufeng Liu, Ningxin Dang, Shiqian Hu, Liping Wu, Chengsheng Zhang, Kai Ye, Bingyin Shi
Journal: Cellular and Molecular Immunology (2021)

Abstract Graves’ orbitopathy (GO), the most severe manifestation of Graves’ hyperthyroidism (GH), is an autoimmune-mediated inflammatory disorder, and treatments often exhibit a low efficacy. CD4+ T cells have been reported to play vital roles in GO progression. To explore the pathogenic CD4+ T cell types that drive GO progression, we applied single-cell RNA sequencing (scRNA-Seq), T cell receptor sequencing (TCR-Seq), flow cytometry, immunofluorescence and mixed lymphocyte reaction (MLR) assays to evaluate CD4+ T cells from GO and GH patients. scRNA-Seq revealed the novel GO-specific cell type CD4+ cytotoxic T lymphocytes (CTLs), which are characterized by chemotactic and inflammatory features. The clonal expansion of this CD4+ CTL population, as demonstrated by TCR-Seq, along with their strong cytotoxic response to autoantigens, localization in orbital sites, and potential relationship with disease relapse provide strong evidence for the pathogenic roles of GZMB and IFN-γ-secreting CD4+ CTLs in GO. Therefore, cytotoxic pathways may become potential therapeutic targets for GO.