tbuckley/cabot-search huggingface dataset:
SARS-CoV-2 Transmission and Infection Among Attendees of an Overnight Camp — Georgia, June 2020
Authors: Christine M. Szablewski, Karen T. Chang, Marie M. Brown, Victoria T. Chu, Anna R. Yousaf, Ndubuisi Anyalechi, Peter A. Aryee, Hannah L. Kirking, Maranda Lumsden, Erin Mayweather, Clinton J. McDaniel, Robert Montierth, Asfia Mohammed, Noah G. Schwartz, Jaina A. Shah, Jacqueline E. Tate, Emilio Dirlikov, Cherie Drenzek, Tatiana M. Lanzieri, Rebekah J. Stewart
Journal: MMWR Morbidity and Mortality Weekly Report (2020)

Limited data are available about transmission of SARS-CoV-2, the virus that causes coronavirus disease 2019 (COVID-19), among youths. During June 17-20, an overnight camp in Georgia (camp A) held orientation for 138 trainees and 120 staff members; staff members remained for the first camp session, scheduled during June 21-27, and were joined by 363 campers and three senior staff members on June 21. Camp A adhered to the measures in Georgia's Executive Order* that allowed overnight camps to operate beginning on May 31, including requiring all trainees, staff members, and campers to provide documentation of a negative viral SARS-CoV-2 test ≤12 days before arriving. Camp A adopted most† components of CDC's Suggestions for Youth and Summer Camps§ to minimize the risk for SARS-CoV-2 introduction and transmission. Measures not implemented were cloth masks for campers and opening windows and doors for increased ventilation in buildings. Cloth masks were required for staff members. Camp attendees were cohorted by cabin and engaged in a variety of indoor and outdoor activities, including daily vigorous singing and cheering. On June 23, a teenage staff member left camp A after developing chills the previous evening. The staff member was tested and reported a positive test result for SARS-CoV-2 the following day (June 24). Camp A officials began sending campers home on June 24 and closed the camp on June 27. On June 25, the Georgia Department of Public Health (DPH) was notified and initiated an investigation. DPH recommended that all attendees be tested and self-quarantine, and isolate if they had a positive test result.
Transmission of SARS-CoV-2 in Australian educational settings: a prospective cohort study
Authors: Kristine Macartney, Helen E Quinn, Alexis J Pillsbury, Archana Koirala, Lucy Deng, Noni Winkler, Anthea L Katelaris, Matthew V N O'Sullivan, Craig Dalton, Nicholas Wood, D Brogan, C Glover, N Dinsmore, A Dunn, A Jadhav, R Joyce, R Kandasamy, K Meredith, L Pelayo, L Rost, G Saravanos, S Bag, S Corbett, M Staff, K Alexander, S Conaty, K Leadbeater, B Forssman, S Kakar, D Dwyer, J Kok, K Chant
Journal: The Lancet Child & Adolescent Health (2020)

School closures have occurred globally during the COVID-19 pandemic. However, empiric data on transmission of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) among children and in educational settings are scarce. In Australia, most schools have remained open during the first epidemic wave, albeit with reduced student physical attendance at the epidemic peak. We examined SARS-CoV-2 transmission among children and staff in schools and early childhood education and care (ECEC) settings in the Australian state of New South Wales (NSW).Laboratory-confirmed paediatric (aged ≤18 years) and adult COVID-19 cases who attended a school or ECEC setting while considered infectious (defined as 24 h before symptom onset based on national guidelines during the study period) in NSW from Jan 25 to April 10, 2020, were investigated for onward transmission. All identified school and ECEC settings close contacts were required to home quarantine for 14 days, and were monitored and offered SARS-CoV-2 nucleic acid testing if symptomatic. Enhanced investigations in selected educational settings included nucleic acid testing and SARS-CoV-2 antibody testing in symptomatic and asymptomatic contacts. Secondary attack rates were calculated and compared with state-wide COVID-19 rates.15 schools and ten ECEC settings had children (n=12) or adults (n=15) attend while infectious, with 1448 contacts monitored. Of these, 633 (43·7%) of 1448 had nucleic acid testing, or antibody testing, or both, with 18 secondary cases identified (attack rate 1·2%). Five secondary cases (three children; two adults) were identified (attack rate 0·5%; 5/914) in three schools. No secondary transmission occurred in nine of ten ECEC settings among 497 contacts. However, one outbreak in an ECEC setting involved transmission to six adults and seven children (attack rate 35·1%; 13/37). Across all settings, five (28·0%) of 18 secondary infections were asymptomatic (three infants [all aged 1 year], one adolescent [age 15 years], and one adult).SARS-CoV-2 transmission rates were low in NSW educational settings during the first COVID-19 epidemic wave, consistent with mild infrequent disease in the 1·8 million child population. With effective case-contact testing and epidemic management strategies and associated small numbers of attendances while infected, children and teachers did not contribute significantly to COVID-19 transmission via attendance in educational settings. These findings could be used to inform modelling and public health policy regarding school closures during the COVID-19 pandemic.NSW Government Department of Health.
AB1123 PROGRESSION OF FINGER JOINT CARTILAGE DAMAGE EVALUATED BY ULTRASOUND IN PATIENTS WITH RHEUMATOID ARTHRITIS
Authors: T. Ogura, A. Hirata, S. Takenaka, Y. Inoue, T. Kagtagiri, Y. Takakura, H. Ito, H. Kameda
Journal: Annals of the Rheumatic Diseases (2020)

Background: Cartilage damage in rheumatoid arthritis (RA) has been evaluated by joint space narrowing (JSN) in X-ray, despite the fact that it is not a direct evaluation of cartilage. We have recently reported that direct evaluation of finger joint cartilage thickness evaluated by ultrasound (US) is valid and useful for patients with RA 1) . Objectives: In this study, we aimed to examine the progression of cartilage damage in RA patients. Methods: Forty-six patients with RA who had completed the US evaluation of finger joint cartilage thickness at baseline and after 1 year were included in this study. The cartilage thickness of metacarpophalangeal (MCP) and proximal interphalangeal (PIP) joints of 2nd to 5th fingers were bilaterally visualized and measured at the middle portion of MCP and PIP joints from a longitudinal dorsal view, with approximately 90 degrees flexion. Cartilage thickness was measured from the base of the cartilage to the interface artefact at the cartilage surface by calculating the pixel counts on DICOM images. Results: In patients, 78% were female, the median age was 68 years and the median disease duration of the patients was 6 years. The median DAS28-CRP at baseline was 2.6. The sum of total cartilage thickness from 16 joints per patient ranged from 3.1 to 9.1 mm (median 6.4 mm) at baseline, and it was significantly correlated with disease duration (ρ=-0.423, p=0.003). A significant decrease from the baseline in the cartilage thickness (median -1.6%) was observed after 1 year (p=0.041). Furthermore, patients with persistently moderate/high disease activity for 1 year by DAS28-CRP (n=9) showed a greater decrease in the cartilage thickness than the remaining patients with controlled disease activity (n=37) (median -5.9% versus -1.5%, respectively, p=0.029). Conclusion: This study further supported the validity and usefulness of joint cartilage thickness evaluation by US in patients with RA. References: [1]Ogura T, et al. Arthritis Care Res 2019 Oct 25. Disclosure of Interests: Takehisa Ogura: None declared, Ayako Hirata: None declared, Sayaka Takenaka: None declared, Yuki Inoue: None declared, Takaharu Kagtagiri: None declared, Yuto Takakura: None declared, Hideki Ito: None declared, Hideto Kameda Grant/research support from: Abbvie, Asahi-Kasei, Chugai, Eisai, Mitsubishi-Tanabe and Novartis, Consultant of: Abbvie, Boehringer, Celgene, Eli Lilly, Janssen, Novartis, Sanofi, UCB, Speakers bureau: Abbvie, Asahi-Kasei, BMS, Chugai, Eisai, Eli Lilly, Janssen, Mitsubishi-Tanabe, Novartis and Pfizer
AB0379 IS MYCOPHENOLATE SODIUM (MYFORTIC) SIMILARLY EFFECTIVE AS MYCOPHENOLATE MOFETIL (CELLCEPT) IN TREATMENT OF LUPUS NEPHRITIS? EXPERIENCE FROM NON-MEDICAL SWITCHING REAL WORLD DATA IN TAIWAN
Authors: W. N. Huang, Y. M. Chen, W. T. Hung, K. T. Tang, Y. W. Liao, Y. H. Chen
Journal: Annals of the Rheumatic Diseases (2020)

Background: Lupus nephritis is the most important predictive factor of morbidity and mortality in SLE. Though Mycophenolate mofetil is recommended for induction and maintenance treatment of class III, IV V lupus nephritis, it is not approved by US or Taiwan FDA (TFDA). In previous reports of kidney transplantation, no efficacy differences were observed between mycophenolate sodium (Myfortic) and mycophenolate mofetil (Cellcept). However, no clinical trial was conducted to compare these two widely-used mycophenolic acid derivatives in lupus nephritis. In December, 2016, TFDA approved Mycophenolate sodium in treatment of lupus nephritis. For reimbursement issue, patients treated with mycophenolate mofetil were non-medically switched to mycophenolate sodium in Taiwan. Objectives: To compare the treatment efficacy of mycophenolate mofetil and mycophenolate sodium in lupus nephritis patients with non-medical switching. Methods: Between 2016 and 2018, a retrospective observational study enrolled 50 biopsy-proven LN patients in Taichung Veterans General Hospital, Taiwan. All these patients were initially treated with Cellcept for at least one year. Treatment response was evaluated by urinalysis and daily urine protein one year before and after switching to Myfortic. Results: Before switching, 72% patients were classified as responder if complete remission or partial remission were achieved, while 28% patients were categorized as non-responders (Table 1). After switching to Myfortic, 75% of the responder group achieved or maintained complete remission or partial response. In for non-responder group, 85.7% exhibited complete remission or partial response (Table 2). We did not observe new safety signals after switching. Table 2. Laboratory features Non-responder (N=14) Responder* (N=36) Total (n=50) p value Age 31.12±11.48 32.58±9.39 0.660 Female 23(88.5%) 20(76.9%) 43(82.7%) 0.465 Daily urine protein (g) 4.44±4.40 4.43±3.81 0.835 Creatine (mg/dl) 1.44±0.92 1.22±1.16 0.212 Renal pathology class 0.649 III 6(23.1%) 4(15.4%) 10(19.2%) III+V 2(7.7%) 4(15.4%) 6(11.5%) IV 16(61.5%) 15(57.7%) 31(59.6%) IV+V 2(7.7%) 3(11.5%) 5(9.6%) *complete remission and partial remission. Table 1. Comparative analysis of 328 SLE patients with and without lupus fatigue Initial treatment with Cellcept Non-responder Responder p value Non-medical switch to Myfortic 0.705 Non-responder 2(14.3) 9(25) Responder 12(85.7) 27(75) Conclusion: This real-world data indicated similar efficacy of Cellcept and Myfortic. Further prospective study is needed to confirm our findings. Disclosure of Interests: None declared
VPS4B mutation impairs the osteogenic differentiation of dental follicle cells derived from a patient with dentin dysplasia type I
Authors: Qiang Li, Fangli Lu, Tianxuan Chen, Ke Zhang, Yuping Lu, Xiaocong Li, Yingying Wang, Ling Liu, Qing Tian, Fu Xiong, Dong Chen
Journal: International Journal of Oral Science (2020)

A splicing mutation in VPS4B can cause dentin dysplasia type I (DD-I), a hereditary autosomal-dominant disorder characterized by rootless teeth, the etiology of which is genetically heterogeneous. In our study, dental follicle cells (DFCs) were isolated and cultured from a patient with DD-I and compared with those from an age-matched, healthy control. In a previous study, this DD-I patient was confirmed to have a loss-of-function splicing mutation in VPS4B (IVS7 + 46C > G). The results from this study showed that the isolated DFCs were vimentin-positive and CK14-negative, indicating that the isolated cells were derived from the mesenchyme. DFCs harboring the VPS4B mutation had a significantly higher proliferation rate from day 3 to day 8 than control DFCs, indicating that VPS4B is involved in cell proliferation. The cells were then replenished with osteogenic medium to investigate how the VPS4B mutation affected osteogenic differentiation. Induction of osteogenesis, detected by alizarin red and alkaline phosphatase staining in vitro, was decreased in the DFCs from the DD-I patient compared to the control DFCs. Furthermore, we also found that the VPS4B mutation in the DD-I patient downregulated the expression of osteoblast-related genes, such as ALP, BSP, OCN, RUNX2, and their encoded proteins. These outcomes confirmed that the DD-I-associated VPS4B mutation could decrease the capacity of DFCs to differentiate during the mineralization process and may also impair physiological root formation and bone remodeling. This might provide valuable insights and implications for exploring the pathological mechanisms underlying DD-I root development.
Role of IL‐25, IL‐33, and TSLP in triggering united airway diseases toward type 2 inflammation
Authors: Haiyu Hong, Shumin Liao, Fenghong Chen, Qintai Yang, De‐Yun Wang
Journal: Allergy (2020)

Under the concept of "united airway diseases," the airway is a single organ wherein upper and lower airway diseases are commonly comorbid. The upper and lower airways are lined with respiratory epithelium that plays a vital role in immune surveillance and modulation as the first line of defense to various infective pathogens, allergens, and physical insults. Recently, there is a common hypothesis emphasizing epithelium-derived cytokines, namely IL-25, IL-33, and TSLP, as key regulatory factors that link in immune-pathogenic mechanisms of allergic rhinitis (AR), chronic rhinosinusitis (CRS), and asthma, mainly involving in type 2 inflammatory responses and linking innate and adaptive immunities. Herein, we review studies that elucidated the role of epithelium-derived triple cytokines in both upper and lower airways with the purpose of expediting better clinical treatments and managements of AR, CRS, asthma, and other associated allergic diseases via applications of the modulators of these cytokines.
Transcatheter tricuspid valve repair in the setting of heart failure with preserved or reduced left ventricular ejection fraction
Authors: Karl‐Patrik Kresoja, Alexander Lauten, Mathias Orban, Karl‐Philipp Rommel, Brunilda Alushi, Christian Besler, Daniel Braun, Matthias Unterhuber, Karl Stangl, Ulf Landmesser, Steffen Massberg, Holger Thiele, Jörg Hausleiter, Philipp Lurz
Journal: European Journal of Heart Failure (2020)
Abstract AP08: DEVELOPMENT OF A MULTI-PROTEIN CLASSIFIER FOR OVARIAN CANCER DETECTION BY SIMULTANEOUS MEASUREMENT OF 92 SERUM PROTEINS ON PROSEEK MULTIPLEX ONCOLOGY II PLATES
Authors: Amy P.N. Skubitz, Kristin L.M. Boylan, Kate Geschwind, Qing Cao, Timothy K. Starr, Melissa A. Geller, Joseph Celestino, Robert C. Bast, Karen H. Lu, Joseph S. Koopmeiners
Journal: Clinical Cancer Research (2019)

Abstract There are no FDA approved screening tools for detecting ovarian cancer in the general population. The two best known ovarian cancer biomarkers, CA125 and HE4, are neither adequately sensitive nor specific when used alone to screen the general population for early stage disease. By using a combination of protein biomarkers for screening, it may be possible to increase the sensitivity and specificity over CA125 alone. In this study, we used Proseek Multiplex Oncology II plates to simultaneously measure the expression of 92 cancer-related proteins in serum using proximity extension assays. This technology combines the sensitivity of the polymerase chain reaction with the specificity of antibody-based detection methods, allowing multiplex biomarker detection and high throughput quantification. We analyzed one microliter of serum from 61 women with advanced stage high grade serous ovarian cancer and compared the values obtained to 88 age-matched healthy women. Principle component analysis and unsupervised hierarchical clustering separated the ovarian cancer patients from the healthy, with minimal misclassification. Data from the Proseek plates for CA125 levels exhibited a strong correlation with previously measured clinical values for CA125 (correlation coefficient of 0.91). CA125 and HE4 were detected at low levels in samples from healthy women, while higher levels were observed in the ovarian cancer cases. We identified 52 proteins that differed significantly (p &amp;lt; 0.006) between ovarian cancer and healthy samples; several of which are novel serum biomarkers for ovarian cancer. In total, 40 proteins had an estimated area under the ROC curve of 0.70 or greater. CA125 alone achieved a sensitivity of 93.4% at a specificity of 98%. However, by adding five proteins to CA125, we increased the assay sensitivity to 98.4%, while holding the specificity fixed at 98%. Our data demonstrate that the Proseek technology can replicate the results established by conventional clinical assays for known biomarkers, identify new candidate biomarkers, and improve the sensitivity and specificity of CA125 alone. Citation Format: Amy P.N. Skubitz, Kristin L.M. Boylan, Kate Geschwind, Qing Cao, Timothy K. Starr, Melissa A. Geller, Joseph Celestino, Robert C. Bast Jr., Karen H. Lu, and Joseph S. Koopmeiners. DEVELOPMENT OF A MULTI-PROTEIN CLASSIFIER FOR OVARIAN CANCER DETECTION BY SIMULTANEOUS MEASUREMENT OF 92 SERUM PROTEINS ON PROSEEK MULTIPLEX ONCOLOGY II PLATES [abstract]. In: Proceedings of the 12th Biennial Ovarian Cancer Research Symposium; Sep 13-15, 2018; Seattle, WA. Philadelphia (PA): AACR; Clin Cancer Res 2019;25(22 Suppl):Abstract nr AP08.
Covid-19: Campaigners demand to see contracts for £10bn track and trace services
Authors: Elisabeth Mahase
Journal: BMJ (2020)

Covid-19: Campaigners demand to see contracts for £10bn track and trace services Elisabeth MahaseMore than 100 public figures, including public health experts, academics, journalists, and trade union leaders, have written to England's health and social care secretary demanding that he publish details of the contracts given to private companies to run the national test and trace system for covid-19. 11 We deserve to see the test and trace contracts with private companies.We Own It. 29 Jul 2020.
Modeling the conversion between specific IgE test platforms for nut allergens in children and adolescents
Authors: Jennifer A. Hoang, Alper Celik, Christian Lupinek, Rudolf Valenta, Lucy Duan, Ruixue Dai, May G. Brydges, Aimée Dubeau, Claire Lépine, Samantha Wong, Mara Alexanian‐Farr, Ahuva Magder, Padmaja Subbarao, Julia E. M. Upton, Klara Schmidthaler, Zsolt Szépfalusi, Arun Ramani, Thomas Eiwegger
Journal: Allergy (2020)

Multiplex tests allow for measurement of allergen-specific IgE responses to multiple extracts and molecular allergens and have several advantages for large cohort studies. Due to significant methodological differences, test systems are difficult to integrate in meta-analyses/systematic reviews since there is a lack of datasets with direct comparison. We aimed to create models for statistical integration of allergen-specific IgE to peanut/tree nut allergens from three IgE test platforms.Plasma from Canadian and Austrian children/adolescents with peanut/tree nut sensitization and a cohort of sensitized, high-risk, pre-school asthmatics (total n = 166) were measured with three R&D multiplex IgE test platforms: Allergy Explorer version 1 (ALEX) (Macro Array Dx), MeDALL-chip (Mechanisms of Development of Allergy) (Thermo Fisher), and EUROLINE (EUROIMMUN). Skin prick test (n = 51) and ImmunoCAP (Thermo Fisher) (n = 62) results for extracts were available in a subset. Regression models (Multivariate Adaptive Regression Splines, local polynomial regression) were applied if >30% of samples were positive to the allergen. Intra-test correlations between PR-10 and nsLTP allergens were assessed.Using two regression methods, we demonstrated the ability to model allergen-specific relationships with acceptable measures of fit (r2 = 94%-56%) for peanut and tree nut sIgE testing at the extract and molecular-level, in order from highest to lowest: Ara h 2, Ara h 6, Jug r 1, Ana o 3, Ara h 1, Jug r 2, and Cor a 9.Our models support the notion that quantitative conversion is possible between sIgE multiplex platforms for extracts and molecular allergens and may provide options to aggregate data for future meta-analysis.
Human CLEC9A antibodies deliver NY-ESO-1 antigen to CD141<sup>+</sup> dendritic cells to activate naïve and memory NY-ESO-1-specific CD8<sup>+</sup> T cells
Authors: Kelly-Anne Masterman, Oscar L Haigh, Kirsteen M Tullett, Ingrid M Leal-Rojas, Carina Walpole, Frances E Pearson, Jonathon Cebon, Christopher Schmidt, Liam O'Brien, Nikita Rosendahl, Ghazal Daraj, Irina Caminschi, Eric H Gschweng, Roger P Hollis, Donald B Kohn, Mireille H Lahoud, Kristen J Radford
Journal: Journal for ImmunoTherapy of Cancer (2020)

Background Dendritic cells (DCs) are crucial for the efficacy of cancer vaccines, but current vaccines do not harness the key cDC1 subtype required for effective CD8 + T-cell-mediated tumor immune responses. Vaccine immunogenicity could be enhanced by specific delivery of immunogenic tumor antigens to CD141 + DCs, the human cDC1 equivalent. CD141 + DCs exclusively express the C-type-lectin-like receptor CLEC9A, which is important for the regulation of CD8 + T cell responses. This study developed a new vaccine that harnesses a human anti-CLEC9A antibody to specifically deliver the immunogenic tumor antigen, NY-ESO-1 (New York esophageal squamous cell carcinoma 1), to human CD141 + DCs. The ability of the CLEC9A-NY-ESO-1 antibody to activate NY-ESO-1-specific naïve and memory CD8 + T cells was examined and compared with a vaccine comprised of a human DEC-205-NY-ESO-1 antibody that targets all human DCs. Methods Human anti-CLEC9A, anti-DEC-205 and isotype control IgG4 antibodies were genetically fused to NY-ESO-1 polypeptide. Cross-presentation to NY-ESO-1-epitope-specific CD8 + T cells and reactivity of T cell responses in patients with melanoma were assessed by interferon γ (IFNγ) production following incubation of CD141 + DCs and patient peripheral blood mononuclear cells with targeting antibodies. Humanized mice containing human DC subsets and a repertoire of naïve NY-ESO-1-specific CD8 + T cells were used to investigate naïve T cell priming. T cell effector function was measured by expression of IFNγ, MIP-1β, tumor necrosis factor and CD107a and by lysis of target tumor cells. Results CLEC9A-NY-ESO-1 antibodies (Abs) were effective at mediating delivery and cross-presentation of multiple NY-ESO-1 epitopes by CD141 + DCs for activation of NY-ESO-1-specific CD8 + T cells. When benchmarked to NY-ESO-1 conjugated to an untargeted control antibody or to anti-human DEC-205, CLEC9A-NY-ESO-1 was superior at ex vivo reactivation of NY-ESO-1-specific T cell responses in patients with melanoma. Moreover, CLEC9A-NY-ESO-1 induced priming of naïve NY-ESO-1-specific CD8 + T cells with polyclonal effector function and potent tumor killing capacity in vitro. Conclusions These data advocate human CLEC9A-NY-ESO-1 Ab as an attractive strategy for specific targeting of CD141 + DCs to enhance tumor immunogenicity in NY-ESO-1-expressing malignancies.