tbuckley/cabot-search huggingface dataset:
AB0033 MACROPHAGE ACTIVATION IN PATIENTS WITH ACTIVE RHEUMATOID ARTHRITIS AND SYSTEMIC LUPUS ERYTHEMATOSUS (PRELIMINARY DATA)
Authors: E. Gerasimova, T. Popkova, T. Kirichenko, А . Markin, Y. Markina, D. Gerasimova, A. Bogatyreva, A. Orekhov
Journal: Annals of the Rheumatic Diseases (2021)

Background: The study of the ability of monocytes to activate associated with the clinical activity of immunological markers of inflammation in rheumatoid arthritis (RA) and systemic lupus erythematosus (SLE) will provide important and fundamentally new information on the involvement of these cells in the development of autoimmune rheumatic diseases (ARDs). Objectives: To study macrophage activation in rheumatoid arthritis (RA) and systemic lupus erythematosus (SLE) patients (pts). Methods: A total of 21 active ARDs pts (11 RA, 10 SLE) were enrolled in the study (median age was 55[44; 63] years; disease duration was 8 [2; 14] months). There are 11 pts with early RA (disease duration was ≤12 months), moderate to high activity (DAS28 was 6.1[4.9;6.7]; SDAI was 25(22;31); ACCP was positive in 73% and RF in 87% cases) and 10 pts with active SLE (SLADAI-2K was 7 [6;8]) in the study. All early RA pts and 4 SLE pts were not treated with glucocorticoids and disease-modifying antirheumatic drugs. Six SLE pts received low-dose glucocorticoids and hydroxychloroquine. All pts were assessed for macrophage activation and laboratory data: ESR, RF, ACCP, CRP, ANA, anti-dsDNA. Isolation of monocytes was carried out according to the standard procedure for obtaining a leukocyte fraction in a Ficoll gradient and subsequent selection of CD14 + cells using magnetic separation. After isolation, the cells were cultured in X-Vivo medium. To assess the degree of monocyte activation, cells were stimulated by the addition of LPS. The value of monocyte activation was expressed as a ratio of the level of secretion of proinflammatory cytokines by monocytes cultured with and without LPS addition. Secretion levels were determined by ELISA. The belonging of the isolated cells to CD14 + monocytes was additionally confirmed by flow cytometry. Results: Macrophage activation was 2.6 (2.0;5.4) and 4.8 (2.8;7.3) in RA and SLE pts, respectively (p&gt;0.05). In RA and SLE pts macrophage activation was independent of age, sex, body mass index, traditional risk factors (arterial hypertension, overweight, smoking, family history of cardiovascular diseases), RA activity scores (DAS28, SDAI), and SLADAI-2K. No association was found between macrophage activation and levels of ESR, RF, ACCP, CRP, ANA, and anti-dsDNA. Conclusion: No differences in macrophage activation were found in RA and SLE pts. Macrophage activation was independent of age, sex, traditional risk factors, and ARD-related parameters. A study on a larger number of pts will clarify the link between macrophage activation and autoimmune disorders. This work was supported by the Russian Science Foundation (Grant № 21-15-00225). Disclosure of Interests: None declared
POS1232 COVID-19 IN PATIENTS WITH SYSTEMIC SCLEROSIS: ONE RHEUMATOLOGY CENTER EXPERIENCE
Authors: M. Starovoytova, O. Desinova, L. P. Ananyeva, O. Koneva, L. Garzanova, O. Ovsyannikova, R. Shayakhmetova, V. Babak, T. Beketova
Journal: Annals of the Rheumatic Diseases (2021)

Background: Severe Acute Respiratory Syndrome-Coronavirus-2 (SARS-CoV-2) virus infection or COVID-19 is a serious problem for patients with systemic autoimmune diseases Given the serious complications, including acute lung injury, patients with systemic sclerosis (SSc), especially SSs associated with interstitial lung disease (ILD), may represent a high risk group for infection and the development of severe COVID-19. Objectives: We present an analysis of the COVID-19 course and outcomes in 110 SSc pts. Methods: The study included 147 patients with SSc. The information was clarified by means of telephone survey after 10 months of the pandemic (December 2020). Covid-19 was diagnosed when confirmed by positive oral /nasopharyngeal swab, in the presence of positive antibodies and/or characteristic symptoms, and data from chest computed tomography (CT). 110 pts (77%) out of 147 patients in the SSc registry, gave the necessary information. COVID-19 was diagnosed in 59 pts (53 %). 42 pts (71%) had SSc-ILD. Pts mean age was 54.96 (s.d.11, min 31, max 79), 83% women (49 women and 10 men). 38 pts (65%) had a limited form of SSc, 15 (26%) pts had diffuse form SSc, 6% had overlap (SSc-polymyositis (PM) and SSc had rheumatoid arthritis (RA) and 3% had visceral form of SSc). All patients received low-dose prednisone, and more than half of the pts received immunosuppressive therapy. Rituximab therapy was performed in 24 pts (41%). Results: Almost all patients had positive swab from the oral cavity/nasopharynx. And only in 4 (7%) pts nasopharyngeal swabs were negative, in these patients specific antibodies and characteristic CT changes were detected. Chest CT was performed in 51 (86%) pts. Novel coronavirus pneumonia developed in the vast majority of pts - in 46 (78 %) pts. CT1 (up to 25% of lung lesions) had 10 (17%) pts, CT2 (25-50%) – 21(36%) pts, CT 3 (50-75%) – 15(25%) pts. In 5 (8.5%) pts no changes were detected on CT. The course of COVID-19 was mild and moderate (20 (34%) pts and 18 (31%) pts respectively), severe course was observed in 21 (35%) pts, including fatal in 12 (20%) pts. Among the deceased pts, only 1 patient with SSc-PM had not had ILD, but 7 patients had been treated with rituximab. Conclusion: SSc SARS-CoV-2-infected patients may be at risk of severe disease and mortality due to the frequent presence of ILD and the frequent use of immunosuppressive, including biological, therapy. Disclosure of Interests: None declared
In vivo delivery of CRISPR-Cas9 therapeutics: Progress and challenges
Authors: Matthew Behr, Jing Zhou, Bing Xu, Hongwei Zhang
Journal: Acta Pharmaceutica Sinica B (2021)

Within less than a decade since its inception, CRISPR-Cas9-based genome editing has been rapidly advanced to human clinical trials in multiple disease areas. Although it is highly anticipated that this revolutionary technology will bring novel therapeutic modalities to many diseases by precisely manipulating cellular DNA sequences, the low efficiency of in vivo delivery must be enhanced before its therapeutic potential can be fully realized. Here we discuss the most recent progress of in vivo delivery of CRISPR-Cas9 systems, highlight innovative viral and non-viral delivery technologies, emphasize outstanding delivery challenges, and provide the most updated perspectives.
Deep learning-based detection of eosinophilic esophagitis
Authors: Pedro Guimarães, Andreas Keller, Tobias Fehlmann, Frank Lammert, Markus Casper
Journal: Endoscopy (2021)

For eosinophilic esophagitis (EoE), a substantial diagnostic delay is still a clinically relevant phenomenon. Deep learning-based algorithms have demonstrated potential in medical image analysis. Here we establish a convolutional neuronal network (CNN)-based approach that can distinguish the appearance of EoE from normal findings and candida esophagitis.We trained and tested a CNN using 484 real-world endoscopic images from 134 subjects consisting of three classes (normal, EoE, and candidiasis). Images were split into two completely independent datasets. The proposed approach was evaluated against three trainee endoscopists using the test set. Model-explainability was enhanced by deep Taylor decomposition.Global accuracy (0.915 [95 % confidence interval (CI) 0.880-0.940]), sensitivity (0.871 [95 %CI 0.819-0.910]), and specificity (0.936 [95 %CI 0.910-0.955]) were significantly higher than for the endoscopists on the test set. Global area under the receiver operating characteristic curve was 0.966 [95 %CI 0.954-0.975]. Results were highly reproducible. Explainability analysis found that the algorithm identified the characteristic signs also used by endoscopists.Complex endoscopic classification tasks including more than two classes can be solved by CNN-based algorithms. Therefore, our algorithm may assist clinicians in making the diagnosis of EoE.
AniProtDB: A Collection of Consistently Generated Metazoan Proteomes for Comparative Genomics Studies
Authors: Sofia N Barreira, Anh-Dao Nguyen, Mark T Fredriksen, Tyra G Wolfsberg, R Travis Moreland, Andreas D Baxevanis
Journal: Molecular Biology and Evolution (2021)

To address the void in the availability of high-quality proteomic data traversing the animal tree, we have implemented a pipeline for generating de novo assemblies based on publicly available data from the NCBI Sequence Read Archive, yielding a comprehensive collection of proteomes from 100 species spanning 21 animal phyla. We have also created the Animal Proteome Database (AniProtDB), a resource providing open access to this collection of high-quality metazoan proteomes, along with information on predicted proteins and protein domains for each taxonomic classification and the ability to perform sequence similarity searches against all proteomes generated using this pipeline. This solution vastly increases the utility of these data by removing the barrier to access for research groups who do not have the expertise or resources to generate these data themselves and enables the use of data from nontraditional research organisms that have the potential to address key questions in biomedicine.
Tumor innervation: peripheral nerves take control of the tumor microenvironment
Authors: Stefan M. Gysler, Ronny Drapkin
Journal: Journal of Clinical Investigation (2021)

In recent decades, cancer research has expanded exponentially beyond the study of abnormally dividing cells to include complex and extensive heterotypic interactions between cancer and noncancer cells that constitute the tumor microenvironment (TME). Modulation of stromal, immune, and endothelial cells by cancer cells promotes proliferation, survival, and metabolic changes that support tumor growth and metastasis. Recent evidence demonstrates that tumors can recruit peripheral nerves to the TME, leading to enhanced tumor growth in a range of cancer models through distinct mechanisms. This process, termed tumor innervation, is associated with an aggressive tumor phenotype and correlates with poor prognosis in clinical studies. Therefore, the peripheral nervous system may play an underrecognized role in cancer development, harboring targetable pathways that warrant investigation. To date, nerves have been implicated in driving proliferation, invasion, metastasis, and immune evasion through locally delivered neurotransmitters. However, emerging evidence suggests that cell-cell communication via exosomes induces tumor innervation, and thus exosomes may also mediate neural regulation of the TME. In this Review, seminal studies establishing tumor innervation are discussed, and known and putative signaling mechanisms between peripheral nerves and components of the TME are explored as a means to identify potential opportunities for therapeutic intervention.
Newly diagnosed and relapsed mantle cell lymphoma: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up
Authors: M. Dreyling, C. Geisler, O. Hermine, H.C. Kluin-Nelemans, S. Le Gouill, S. Rule, O. Shpilberg, J. Walewski, M. Ladetto
Journal: Annals of Oncology (2014)
Miniaturized electromechanical devices for the characterization of the biomechanics of deep tissue
Authors: Enming Song, Zhaoqian Xie, Wubin Bai, Haiwen Luan, Bowen Ji, Xin Ning, Yu Xia, Janice Mihyun Baek, Yujin Lee, Raudel Avila, Huang-Yu Chen, Jae-Hwan Kim, Surabhi Madhvapathy, Kuanming Yao, Dengfeng Li, Jingkun Zhou, Mengdi Han, Sang Min Won, Xinyuan Zhang, Daniel J. Myers, Yongfeng Mei, Xu Guo, Shuai Xu, Jan-Kai Chang, Xinge Yu, Yonggang Huang, John A. Rogers
Journal: Nature Biomedical Engineering (2021)
COVID-19 Severity and COVID-19–Associated Deaths Among Hospitalized Patients with HIV Infection — Zambia, March–December 2020
Authors: Duncan Chanda, Peter A. Minchella, Davies Kampamba, Megumi Itoh, Jonas Z. Hines, Sombo Fwoloshi, Mary Adetinuke Boyd, Kalongo Hamusonde, Lameck Chirwa, Kotey Nikoi, Robert Chirwa, Mpanji Siwingwa, Suilanji Sivile, Khozya D. Zyambo, Aggrey Mweemba, Nyuma Mbewe, Katongo H. Mutengo, Kennedy Malama, Simon Agolory, Lloyd B. Mulenga
Journal: MMWR Morbidity and Mortality Weekly Report (2021)

The effect of HIV infection on COVID-19 outcomes is unclear.Studies in South Africa (1) and the United Kingdom (2) found an independent association between HIV infection and COVID-19 mortality; however, other studies have not found an association between poor COVID-19 outcomes and either HIV status among hospitalized patients (3-5) or HIV-associated factors such as CD4 count, viral load, or type of antiretroviral therapy (ART) (6).The effect of HIV infection on COVID-19 outcomes remains an urgent question in sub-Saharan Africa, where many countries are experiencing dual HIV and COVID-19 epidemics, and capacity to treat severe COVID-19 is limited.Using data from patients with probable or confirmed COVID-19 admitted to specialized treatment centers during March-December 2020 in Zambia, the Zambian Ministry of Health and CDC assessed the relationship between HIV infection and severe COVID-19 and COVID-19associated death.Among 443 patients included in the study, 122 (28%) were HIV-positive, and of these, 91 (89%) were receiving ART at the time of hospitalization.HIV status alone was not significantly associated with severe COVID-19 at admission or during hospitalization or with COVID-19-associated death.However, among HIV-positive persons, those with severe HIV disease were more likely to develop severe COVID-19 and were at increased risk for COVID-19-associated death.Ensuring that persons maintain HIV disease control, including maintaining ART continuity and adherence, achieving viral suppression, and addressing and managing underlying medical conditions, could help reduce COVID-19-associated morbidity and mortality in sub-Saharan Africa.Zambia is a landlocked country in southeastern Africa, with an estimated population of 17.4 million* and a generalized HIV/AIDS epidemic with HIV prevalence among persons aged ≥15 years of 12.1% (7).Beginning in March 2020, patients with a diagnosis of probable or laboratory-confirmed COVID-19 in Zambia were admitted to one of five Zambia Ministry of Health specialized COVID-19 treatment centers located in the capital city of Lusaka (two treatment centers) and in Ndola, Kabwe, and Livingstone.Confirmed cases were those with positive reverse transcription-polymerase chain
SARS-CoV-2 variants of concern partially escape humoral but not T cell responses in COVID-19 convalescent donors and vaccine recipients
Authors: Daryl Geers, Marc C. Shamier, Susanne Bogers, Gerco den Hartog, Lennert Gommers, Nella N. Nieuwkoop, Katharina S. Schmitz, Laurine C. Rijsbergen, Jolieke A. T. van Osch, Emma Dijkhuizen, Gaby Smits, Anouskha Comvalius, Djenolan van Mourik, Tom G. Caniels, Marit J. van Gils, Rogier W. Sanders, Bas B. Oude Munnink, Richard Molenkamp, Herbert J. de Jager, Bart L. Haagmans, Rik L. de Swart, Marion P. G. Koopmans, Robert S. van Binnendijk, Rory D. de Vries, Corine H. GeurtsvanKessel
Journal: Science Immunology (2021)

Infection- or vaccination-induced SARS-CoV-2 S–specific CD4 + T cells are indifferent to the S mutations of variants of concern.
POS0633 DURATION OF STARTING bDMARDs ARE ALMOST 3 TIMES LONGER IN RA PATIENTS THAN PsA PATIENTS: HUR-BIO REAL LIFE RESULTS
Authors: G. K. Yardimci, B. Farisoğullari, E. C. Bolek, E. Bilgin, E. Duran, G. Ayan, Z. Özsoy, G. Sandal Uzun, L. Kiliç, A. Akdoğan, O. Karadag, Ş. A. Bilgen, S. Kiraz, A. İ. Ertenli, U. Kalyoncu
Journal: Annals of the Rheumatic Diseases (2021)

<h3>Background:</h3> Before using biological DMARDs, EULAR suggests the use of synthetic DMARDs (especially methotrexate) for RA and PsA [1-2]. <h3>Objectives:</h3> It was aimed to evaluate the differences of disease duration and csDMARDs till first bDMARD in RA and PsA patients. <h3>Methods:</h3> HUR-BIO (Hacettepe University Biologic Registry) is a prospective, single center database of biological treatments since 2005 and to date 2070 RA and 520 PsA patients have been recorded. Demographic, clinical and laboratory data before bDMARDs of the patients were noted. When investigating the differences between groups, the effects of gender, age and disease duration wereadjusted using two-way ANOVA and ANCOVA tests. The selection was made for the gender, age and for indifference of the relevant groups by using prospensity score matching. <h3>Results:</h3> We incuded 481 RA, and 482 PsA age and gender matched patients in the study. Age, gender and disease duration information were given in the Table 1. 72.8% of the RA patients were RF or anti-CCP positive. Overall, 56.3, 100% of the RA, and PsA patients first biologic therapies were anti-TNFs, respectively. All RA patients started with csDMARDs before bDMARD treatments, whereas 450 of 482 (93.4%) PsA patients. Methotrexate was the anchor csDMARD for both diseases. RA patients more frequently used all csDMARDs included methotrexate, leflunomide, sulphasalazine hydroxychloroquine and corticosteroids as well. Median disease duration till bDMARD treatments in RA and PsA patients were 55 and 18.5 months respectively (p&lt;0.001) (Table 1). <h3>Conclusion:</h3> According to HUR-BIO real life data, for inflammatory arthritis patients who started bDMARDs, the periods of time between diagnosis and bDMARDs were more reasonable (18 months) in PsA patients than RA patient’s periods which were approximately three times longer. RA patients were used much more and longer duration of csDMARDs. This explicit distinction may be explained by synthetic DMARDs on activity differences between the RA and PsA. <h3>References:</h3> [1]Gossec, L., et al., EULAR recommendations for the management of psoriatic arthritis with pharmacological therapies: 2019 update. Ann Rheum Dis, 2020. 79(6): p. 700-712. [2]Smolen, J.S., et al., EULAR recommendations for the management of rheumatoid arthritis with synthetic and biological disease-modifying antirheumatic drugs: 2019 update. Ann Rheum Dis, 2020. 79(6): p. 685-699. <h3>Disclosure of Interests:</h3> None declared
Olaparib Inhibits Tumor Growth of Hepatoblastoma in Patient‐Derived Xenograft Models
Authors: Michael Edward Johnston, Maria Prates Rivas, Delphine Nicolle, Aurore Gorse, Ruhi Gulati, Meenasri Kumbaji, Matthew T. Weirauch, Alexander Bondoc, Stefano Cairo, James Geller, Gregory Tiao, Nikolai Timchenko
Journal: Hepatology (2021)

Hepatoblastoma (HBL) is a devastating pediatric liver cancer with multiple treatment options, but it ultimately requires surgery for a cure. The most malicious form of HBL is a chemo-resistant aggressive tumor that is characterized by rapid growth, metastases, and poor response to treatment. Very little is known of the mechanisms of aggressive HBL, and recent focuses have been on developing alternative treatment strategies. In this study, we examined the role of human chromosomal regions, called aggressive liver cancer domains (ALCDs), in liver cancer and evaluated the mechanisms that activate ALCDs in aggressive HBL.We found that ALCDs are critical regions of the human genome that are located on all human chromosomes, preferentially in intronic regions of the oncogenes and other cancer-associated genes. In aggressive HBL and in patients with Hepatocellular (HCC), JNK1/2 phosphorylates p53 at Ser6, which leads to the ph-S6-p53 interacting with and delivering the poly(adenosine diphosphate ribose) polymerase 1 (PARP1)/Ku70 complexes on the oncogenes containing ALCDs. The ph-S6-p53-PARP1 complexes open chromatin around ALCDs and activate multiple oncogenic pathways. We found that the inhibition of PARP1 in patient-derived xenografts (PDXs) from aggressive HBL by the Food and Drug Administration (FDA)-approved inhibitor olaparib (Ola) significantly inhibits tumor growth. Additionally, this is associated with the reduction of the ph-S6-p53/PARP1 complexes and subsequent inhibition of ALCD-dependent oncogenes. Studies in cultured cancer cells confirmed that the Ola-mediated inhibition of the ph-S6-p53-PARP1-ALCD axis inhibits proliferation of cancer cells.In this study, we showed that aggressive HBL is moderated by ALCDs, which are activated by the ph-S6-p53/PARP1 pathway. By using the PARP1 inhibitor Ola, we suppressed tumor growth in HBL-PDX models, which demonstrated its utility in future clinical models.
Cardiologist from Poland must improve his English before he resumes practice, says tribunal
Authors: Clare Dyer
Journal: BMJ (2021)

A Polish cardiologist who came to work in the UK 15 years ago has been suspended by a medical practitioners tribunal and told he must pass an English language test before he can resume practice.

Tomasz Fryzlewicz, 62, moved to England from Krakow in 2006 and was employed for six years by a company called Cardio Analytics. But his employer reported him to the General Medical Council in 2013, claiming that his English had deteriorated and that he had resisted advice to take lessons.

At the GMC’s urging, he took International English Language Testing System (IELTS) tests but failed to achieve the required score. A medical practitioners tribunal in 2015 imposed conditions on his registration for …
Michael Atkinson: gastroenterology pioneer
Authors: John Illman
Journal: BMJ (2021)

Michael Atkinson’s towering status in gastroenterology was highlighted by a device he made from household utensils. The Atkinson tube helps patients with oesophageal cancer to swallow. But asked on retirement for his outstanding career memory, he replied: “Watching Geoffrey Boycott score his 100th century in the test match at Leeds.”

Atkinson was the stereotypical Yorkshireman. Innately kind and dedicated, he also had his prickly side, according to friends and colleagues. One of the pioneers who turned gastroenterology from something of a clinical sideshow into a wide ranging specialty, he knew what he wanted. Born in Rawdon near Leeds to Herbert, a plumber’s merchant, and Janet, a postmistress, he went to Aireborough Grammar School and was the first member of his family to go to university.

Atkinson studied medicine at University College London during the second world war, winning the Fellowes gold medal as the best student of the year. He became house physician to the illustrious firm of Harold Hemsworth, later secretary to the Medical Research Council, and Max Rosenheim, later Lord Rosenheim, president of the Royal College of Physicians.

Atkinson …
Efficacy and Safety of Intensive Etoposide Aracytine Consolidation Following Rituximab Methotrexate Temozolomide Induction in Newly Diagnosed Primary Central Nervous System Lymphoma
Authors: Rudy Birsen, Estelle Blanc, Barbara Burroni, Chloe Broudin, Lise Willems, Marielle Legoff, Emmanuelle Leray, Sylvain Pilorge, Sawsen Salah, Aude Quentin, Bénédicte Deau-Fisher, Patricia Franchi, Marguerite Vignon, Laurence Mabille, Charles Nguyen, Youlia Kirova, Pascale Varlet, Arnault tauziede-Espariat, Myriam Edjlali, Dezamis Edouard, Carole Soussain, Caroline Houillier, Johan Pallud, Diane Damotte, Didier Bouscary, Jerome Tamburini Bonnefoy
Journal: Blood (2017)
Effect of the use of an endotracheal tube and stylet versus an endotracheal tube alone on first-attempt intubation success: a multicentre, randomised clinical trial in 999 patients
Authors: Samir Jaber, Amélie Rollé, Thomas Godet, Nicolas Terzi, Béatrice Riu, Pierre Asfar, Jeremy Bourenne, Séverin Ramin, Virginie Lemiale, Jean-Pierre Quenot, Christophe Guitton, Eloi Prudhomme, Cyril Quemeneur, Raiko Blondonnet, Mathieu Biais, Laurent Muller, Alexandre Ouattara, Martine Ferrandiere, Piehr Saint-Léger, Thomas Rimmelé, Julien Pottecher, Gerald Chanques, Fouad Belafia, Claire Chauveton, Helena Huguet, Karim Asehnoune, Emmanuel Futier, Elie Azoulay, Nicolas Molinari, Audrey De Jong
Journal: Intensive Care Medicine (2021)