tbuckley/cabot-search huggingface dataset:
Severely ill patients with COVID-19 display impaired exhaustion features in SARS-CoV-2–reactive CD8 <sup>+</sup> T cells
Authors: Anthony Kusnadi, Ciro Ramírez-Suástegui, Vicente Fajardo, Serena J. Chee, Benjamin J. Meckiff, Hayley Simon, Emanuela Pelosi, Grégory Seumois, Ferhat Ay, Pandurangan Vijayanand, Christian H. Ottensmeier
Journal: Science Immunology (2021)

Fewer SARS-CoV-2–reactive memory CD8 + T cells with “exhaustion” features are present in patients with severe versus mild COVID-19.
IL-21 arming potentiates the anti-tumor activity of an oncolytic vaccinia virus in monotherapy and combination therapy
Authors: Tianyue Chen, Xiangqing Ding, Qibin Liao, Nan Gao, Ye Chen, Chen Zhao, Xiaoyan Zhang, Jianqing Xu
Journal: Journal for ImmunoTherapy of Cancer (2021)

Oncolytic viruses (OVs) have shown promise in containing cancer progression in both animal models and clinical trials. How to further improve the efficacy of OVs are intensively explored. Arming OVs with immunoregulatory molecules has emerged as an important means to enhance their oncolytic activities majorly based on the mechanism of reverting the immunosuppressive nature of tumor environment. In this study, we aimed to identify the optimal combination of different OVs and immunomodulatory molecules for solid tumor treatment as well as the underlying mechanism, and subsequently evaluated its potential synergy with other immunotherapies.Panels of oncolytic viruses and cells stably expressing immunoregulatory molecules were separately evaluated for treating solid tumors in mouse model. A tumor-targeted replicating vaccinia virus Tian Tan strain with deletion of TK gene (TTVΔTK) was armed rationally with IL-21 to create rTTVΔTK-IL21 through recombination. CAR-T cells and iNKT cells were generated from human peripheral blood mononuclear cells. The impact of rTTVΔTK-IL21 on tumor-infiltrating lymphocytes was assessed by flow cytometry, and its therapeutic efficacy as monotherapy or in combination with CAR-T and iNKT therapy was assessed in mouse tumor models.IL-21 and TTV was respectively identified as most potent immunomodulatory molecule and oncolytic virus for solid tumor suppression in mouse models. A novel recombinant oncolytic virus that resulted from their combination, namely rTTVΔTK-mIL21, led to significant tumor regression in mice, even for noninjected distant tumor. Mechanistically, rTTV∆TK-mIL21 induced a selective enrichment of immune effector cells over Treg cells and engage a systemic response of therapeutic effect. Moreover, its human form showed a notable synergy with CAR-T or iNKT therapy for tumor treatment when coupled in humanized mice.With a strong potency of shaping tumor microenvironment toward favoring TIL activities, rTTVΔTK-IL21 represents a new opportunity worthy of further exploration in clinical settings for solid tumor control, particularly in combinatorial strategies with other immunotherapies.IL21-armed recombinant oncolytic vaccinia virus has potent anti-tumor activities as monotherapy and in combination with other immunotherapies.
Abstract 10094: Upregulation of Cardiac Beta3-Adrenergic Signaling Promotes Cardiac Aging: Evidence from Chronic Beta3-Adrenoceptor Deficiency Mice
Authors: Zhe Chen, Che Ping Cheng, Peng Zhou, Yixi Liu, Zhi Zhang, Satoshi Masutani, Michael F Callahan, Dalane Kitzman, Heng-Jie Cheng
Journal: Circulation (2019)

Background: Cardiac aging (CA) leads to myocardial function decline with diminished inotropic response to β-adrenergic receptor (AR) stimulation. The molecular mechanism remains unclear. We hypothe...
The European tiered approach for virucidal efficacy testing – rationale for rapidly selecting disinfectants against emerging and re-emerging viral diseases
Authors: Maren Eggers, Ingeborg Schwebke, Miranda Suchomel, Valerie Fotheringham, Jürgen Gebel, Bernhard Meyer, Graziella Morace, Hans Joachim Roedger, Christine Roques, Pilar Visa, Katrin Steinhauer
Journal: Eurosurveillance (2021)

When facing an emerging virus outbreak such as severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), a quick reaction time is key to control the spread. It takes time to develop antivirals and vaccines, and implement vaccination campaigns. Therefore, preventive measures such as rapid isolation of cases and identification and early quarantine of cases’ close contacts—as well as masks, physical distancing, hand hygiene, surface disinfection and air control—are crucial to reduce the risk of transmission. In this context, disinfectants and antiseptics with proven efficacy against the outbreak virus should be used. However, biocidal formulations are quite complex and may include auxiliary substances such as surfactants or emollients in addition to active substances. In order to evaluate disinfectants’ efficacy objectively, meaningful efficacy data are needed. Therefore, the European Committee for Standardisation technical committee 216 ‘Chemical disinfectants and antiseptics’ Working Group 1 (medical area) has developed standards for efficacy testing. The European tiered approach grades the virucidal efficacy in three levels, with corresponding marker test viruses. In the case of SARS-CoV-2, disinfectants with proven activity against vaccinia virus, the marker virus for the European claim ‘active against enveloped viruses’, should be used to ensure effective hygiene procedures to control the pandemic.
Physicians' Conflicts of Interest
Authors: M A Rodwin
Journal: New England Journal of Medicine (1989)

Conflicts between physicians' personal financial interests and those of their patients are now becoming a prominent issue in U.S. health care policy and medical ethics. Physicians' conflicts of interest have been discussed in the Journal and elsewhere.1 2 3 4 5 6 7 8 9 10 11 12 The Institute of Medicine has addressed the problem.13 So has the American College of Physicians.14 The American Medical Association has issued reports and opinions.15 16 17 Congress is now considering legislation that would prohibit physicians from referring Medicare patients to facilities in which they have a financial interest.18 19 20 Conflicts of interest are ubiquitous, and some should be tolerated because eliminating them would cause patients more . . .
Association between human papillomavirus vaccination and serious adverse events in South Korean adolescent girls: nationwide cohort study
Authors: Dongwon Yoon, Ji-Ho Lee, Hyesung Lee, Ju-Young Shin
Journal: BMJ (2021)

Abstract Objective To evaluate the association between human papillomavirus (HPV) vaccination and serious adverse events in adolescent girls in South Korea. Design Cohort study. Setting A large linked database created by linking the Korea Immunization Registry Information System and the National Health Information Database, between January 2017 and December 2019. Participants 441 399 girls aged 11-14 years who had been vaccinated in 2017: 382 020 had been vaccinated against HPV and 59 379 had not been vaccinated against HPV. Main outcome measures Outcomes were 33 serious adverse events, including endocrine, gastrointestinal, cardiovascular, musculoskeletal, haematological, dermatological, and neurological diseases. A cohort design was used for the primary analysis and a self-controlled risk interval design for the secondary analysis; both analyses used a risk period of one year after HPV vaccination for each outcome. Incidence rate and adjusted rate ratios were estimated using Poisson regression in the primary analysis, comparing the HPV vaccinated group with the HPV unvaccinated group, and adjusted relative risks were estimated using conditional logistic regression in the secondary analysis. Results Among the 33 predefined serious adverse events, no associations were found with HPV vaccination in the cohort analysis, including Hashimoto’s thyroiditis (incidence rate per 100 000 person years: 52.7 v 36.3 for the vaccinated and unvaccinated groups; adjusted rate ratio 1.24, 95% confidence interval 0.78 to 1.94) and rheumatoid arthritis (incidence rate per 100 000 person years: 168.1 v 145.4 for the vaccinated and unvaccinated groups; 0.99, 0.79 to 1.25), with the exception of an increased risk observed for migraine (incidence rate per 100 000 person years: 1235.0 v 920.9 for the vaccinated and unvaccinated groups; 1.11, 1.02 to 1.22). Secondary analysis using self-controlled risk intervals confirmed no associations between HPV vaccination and serious adverse events, including migraine (adjusted relative risk 0.67, 95% confidence interval 0.58 to 0.78). Results were robust to varying follow-up periods and for vaccine subtypes. Conclusions In this nationwide cohort study, with more than 500 000 doses of HPV vaccines, no evidence was found to support an association between HPV vaccination and serious adverse events using both cohort analysis and self-controlled risk interval analysis. Inconsistent findings for migraine should be interpreted with caution considering its pathophysiology and the population of interest.
Preparation of Stretchable Nanofibrous Sheets with Sacrificial Coaxial Electrospinning for Treatment of Traumatic Muscle Injury
Authors: Oanh‐Vu Pham‐Nguyen, Young Ju Son, Tae‐wan Kwon, Junhyung Kim, Yun Chan Jung, Jong Bae Park, Byung‐Jae Kang, Hyuk Sang Yoo
Journal: Advanced Healthcare Materials (2021)

Traumatic muscle injury with massive loss of muscle volume requires intramuscular implantation of proper scaffolds for fast and successful recovery. Although many artificial scaffolds effectively accelerate formation and maturation of myotubes, limited studies are showing the therapeutic effect of artificial scaffolds in animal models with massive muscle injury. In this study, improved myotube differentiation is approved on stepwise stretched gelatin nanofibers and applied to damaged muscle recovery in an animal model. The gelatin nanofibers are fabricated by a two-step process composed of co-axial electrospinning of poly(ɛ-caprolactone) and gelatin and subsequent removal of the outer shells. When stepwise stretching is applied to the myoblasts on gelatin nanofibers for five days, enhanced myotube formation and polarized elongation are observed. Animal models with volumetric loss at quadriceps femoris muscles (>50%) are transplanted with the myotubes cultivated on thin and flexible gelatin nanofiber. Treated animals more efficiently recover exercising functions of the leg when myotubes and the gelatin nanofiber are co-implanted at the injury sites. This result suggests that mechanically stimulated myotubes on gelatin nanofiber is therapeutically feasible for the robust recovery of volumetric muscle loss.
Dynamic of Telomeric Parameters in Relapsing or Refractory (R/R) Chronic Lymphocytic Leukemia (CLL), an Analysis of the Filo ICLL001 Bomp Trial
Authors: Laura Bounaix, Andrei Tchirkov, Florence Nguyen-Khac, Patricia Combes, Pierre Feugier, Laurence Sanhes, Marie-Sarah Dilhuydy, Hussam Saad, Loic Ysebaert, Choquet Sylvain, Jean-Pierre Vilque, Annie Brion, Carla Araujo, Emmanuelle Ferrant, Brigitte Dreyfus, Alain Jacques Delmer, Malgorzata Truchan-Graczyk, Stéphane Leprêtre, Sophie de Guibert, Romain Guieze, Lauren Veronese, Richard Lemal, Philippe Vago, Jacques-Olivier Bay, Marc G. Berger, Anna Schuh, Christophe Ferrand, Roselyne Delepine, Véronique Leblond, Olivier Tournilhac
Journal: Blood (2017)
FRI0021 Combination therapy with cyclosporin-a and methotrexate in patients with early potentially aggressive rheumatoid arthritis, a randomised double blind placebo controlled trial
Authors: AH Gerards, RB Landewé, AP Prins, GA Bruijn, HS Goei Thé, BA Dijkmans
Journal: Annals of the Rheumatic Diseases (2001)

<h3>Background</h3> Patients with advanced RA with a suboptimal response on low dose methotrexate (MTX) have shown to respond well after the addition of cyclosporin-A (CsA).<sup>1</sup> The combination of CsA and MTX has never been tested in a parallel design in patients with early RA. <h3>Objectives</h3> To assess in patients with early, and potentially aggressive RA whether combination therapy with CsA and MTX compared to CsA mono therapy, results in a higher number of clinical improvements. <h3>Methods</h3> 120 RA-patients with active disease who were rheumatoid factor positive (95%) and/or had signs of radiological damage (49%) received CsA and MTX or CsA and placebo for 48 weeks. MTX was started ad a dose of 7.5 mg/week, and increased to 15 mg/wk at week 16. CsA was started at a dose of 2.5 mg/kg/day and increased to a maximum of 5 mg/kg/day. Patients who did not have an ACR20 response after 24 weeks were withdrawn. ACR responses at the 20%, 50% and 70% levels were calculated on basis of intention to treat with the last visit put forward in case of premature discontinuation. <h3>Results</h3> Baseline demography was comparable between the two groups. 26 patients in the CsA and MTX group and 27 patients in the CsA and placebo group stopped study medication because of lack of efficacy (14 vs. 21, p = 0.23) or adverse events (12 vs. 6, p = 0.20). Data from week 48 are shown in the Table 1. <h3>Conclusion</h3> In patients with early, potentially aggressive RA, CsA and MTX combination therapy, compared to CsA mono therapy, results in a higher number of major clinical improvements. <h3>Reference</h3> Tugwell, <i>et al</i>. NEJM 1995;3333:137–41
Efficacy and safety of lenvatinib in the real-world treatment of hepatocellular carcinoma: Results from a Canadian multicenter database (HCC CHORD).
Authors: Carla Pires Amaro, Michael J Allen, Jennifer J. Knox, Erica S Tsang, Howard John Lim, Richard M. Lee-Ying, Jessica Qian, Brandon M. Meyers, Alia Thawer, Sulaiman Mohammed Saif Al-Saadi, Tina Hsu, Ravi Ramjeesingh, Hatim Karachiwala, Tasnima Abedin, Vincent C. Tam
Journal: Journal of Clinical Oncology (2021)

275 Background: The REFLECT trial establishedlenvatinib (LEN) as a first-line treatment option for hepatocellular carcinoma (HCC). Compared to sorafenib (S), LEN has a higher objective response rate (ORR) and progression-free survival (PFS) with a slightly different toxicity profile. The aim of this study was to gather data regarding the efficacy and safety of LEN when used in the real-world treatment of HCC. To our knowledge, this is the first study to examine LEN use in HCC patients treated outside of Asia. Methods: HCC patients treated with LEN from 10 cancer centers in the Canadian provinces of British Columbia, Alberta, Ontario and Nova Scotia between July 2018 to July 2020 were included. Overall survival (OS), PFS, disease control rate (DCR) and ORR were retrospectively analyzed and compared across first- and second-to-fourth line use of LEN. ORR was determined radiographically according to the treating physician´s opinion in clinical notes and not RECIST 1.1 or mRECIST. Toxicities were also examined. Results: A total of 220 patients were included in this analysis. Median age was 67 years, 80% were men and 25.5% East Asian. The most frequent causes of liver disease were hepatitis C (37%) and B (26%). 62% of patients received any localized treatment before LEN, of those 26% had TACE, 15% TARE and 7.7% had liver transplant. Before starting LEN 29% of patients were ECOG 0 and 59% were ECOG 1. Most patients were Child-Pugh A (81%) and BCLC stage C (75.5%). Main portal vein invasion was present in 14% of the patients. Median follow-up was 4.5 months. A total of 173 patients (79%) received LEN as first line therapy and 47 patients (21%) were treated in second-to-fourth line. Of patients receiving LEN in first line, 22 (13%) started treatment with S, but switched to LEN before progression due to poor tolerance of S. ORR, DCR, PFS and OS are shown in the table. Toxicities occurred in 86% of patients and led to dose reductions in 76 (35%) patients and drug discontinuation in 53 (24%) patients. The most common side effects were fatigue (59%), hypertension (41%), decreased appetite (25%) and diarrhea (22%). Conclusions: Outcomes of HCC patients treated in Canada with LEN in the first line are comparable to those demonstrated in the REFLECT trial, despite the inclusion of Child-Pugh B and ECOG &gt;1 patients. LEN use in second or later lines also showed similar outcomes, although more conclusions are difficult to draw due to the small numbers. LEN appears to be effective and safe in real world practice outside of Asia in first- and second-to-fourth line treatment of HCC. [Table: see text]
THU0217 Joint hipermobility sindrome: a prospective study of articular and non-rheumatic manifestation in a venezuelan population
Authors: F Riano, O Sanchez, N Pena, Z Tinedo
Journal: Annals of the Rheumatic Diseases (2001)

<h3>Background</h3> <h3>Objectives</h3> Although Joint Hypermobility Sindrome (JHS) is a common condition, there are clearly a number of articular and non-articular manifestations. Because of this, one study of subjects with JHS was performed in our country. <h3>Methods</h3> A prospective, descriptive and analytical of 41 patients attending our Unit from February up to September 1999, and who fulfilled the Beighton Scale for JHS (Beighton P, Grahame R, Bird H (1999) Assessment of hipermobility. In Beighton P (ed) Hypermobility of Joints. Spring, London, pp:9–22) was made. The mean age was 32 years, there were 35 females (85.4%) and 6 males (14.6%). All over the group were evaluated through Beighton Scale (BS), being 4 points the lowest and 9 points the highest. All subjects were examined for echocardiogram and a gynaecological exam was performed in all sexually active women. <h3>Results</h3> 11 patients (26.8%) had 9 points in the BS and 1 patient (2.4%), being the mean of the group of 6 points. The dorsiflexion of fifth finger was found in all subjects. When comparing passive apposition of the thumb of the flexor aspect of the forearm, with the highest point, there was a good correlation (p = 0.003). Patients under 30 years had higher points in the BS (p = 0.005). Arthralgia was present in 29 subjects (70.78%), mainly in women (p = 0.001). Flat feet was found in 23 patients (56.09%) and Marfanoid habitus in 23 patients. Mitral valve prolapse (MVP) was found in 24 patients (58.53%), the great majority under 30 years and with higher points in the BS. Uterine prolapse was diagnosed in 12 women of the 24 examined (50.0%), most of them over 30 years, no significance correlation was showed between uterine prolapse and points in the BS. <h3>Conclusion</h3> In our study arthralgias particularly of the knees was found, and among extrarticular MVP was the commonest one. We also found a higher incidence of uterine prolapse than expected for women in this age.
Erratum. Coronary Artery Disease and Type 2 Diabetes: A Proteomic Study. Diabetes Care 2020;43:843–851
Authors: Giulia Ferrannini, Maria Laura Manca, Marco Magnoni, Felicita Andreotti, Daniele Andreini, Roberto Latini, Attilio Maseri, Aldo P. Maggioni, Rachel M. Ostroff, Stephen A. Williams, Ele Ferrannini
Journal: Diabetes Care (2021)

In the above article, all mentions of “cartilage intermediate-layer protein” refer to “cartilage intermediate-layer protein 2.” The isoform number was misstated in the abstract and one place in the …
SAT0026 Is radiographic examination sufficient for detection of non traumatic spinal fractures in ankylosig spondylitis: comparison of radiographic and mri findings
Authors: H Przepiera-Bedzak, L Cyrylowski, M Brzosko
Journal: Annals of the Rheumatic Diseases (2001)

<h3>Background</h3> <h3>Objectives</h3> To compare plain radiographic and MRI findings in evaluation of non traumatic spinal fractures in patients with ankylosing spondylitis (AS), and to find correlation between spinal fractures and disease activity, age of patients, and disease duration. <h3>Methods</h3> 21 males and 2 females with AS, mean aged 49.8, were studied. Lateral radiographs and MRI examinations of lumbar, thoracic and cervical spine were performed in all patients. To detect vertebral body fractures with radiographs, the anterior, posterior and central heights of each vertebral body were measured. The ratio of each height to that of the two adjacent vertebrae, the ratio of the anterior height to the posterior height and of the central height to the posterior height were calculated. The subjects were considered to have fracture if any of these ratios was less than 0,85 for lumbar spine and less than 0,8 for thoracic and cervical spine. We assessed also the following indexes of disease activity: BASFI, BASDAI, BASG-t, BASG-6, BSMI. <h3>Results</h3> Total 25 fractures were found with the radiographic method: 7 fractures in lumbar spine, 15 in thoracic and 3 in cervical. The MRI examinations revealed total 51 fractures: 24 fractures in lumbar spine, 18 in thoracic and 9 in cervical. Out of 25 fractures detected by X-ray examination, MRI confirmed the site of fracture only in 10 (40%). Age of patients and disease duration correlated positively with total number of fractures, number of fractures in lumbar spine and number of fractures in thoracic detected by MRI. There was no such correlation for fractures detected by X-ray. Assessing indexes of disease activity we found positive correlation between BASFI, BASDAI, BASMI and total number of fractures and number of fractures in lumbar spine detected by MRI. <h3>Conclusion</h3> The significant difference between radiographic and MRI findings in detecting of vertebral fractures was found. The results suggest that plain X-rays cannot be considered as a sufficient method for detection vertebral fractures in patients with AS. MRI should be considered as the method of choice in revealing spinal fractures in AS patients. Disease activity may contribute in developing of non – traumatic spinal fractures in this group of patients.