tbuckley/cabot-search huggingface dataset:
Diagnostic accuracy of point-of-care tests in acute community-acquired lower respiratory tract infections. A systematic review and meta-analysis
Authors: Elisa Gentilotti, Pasquale De Nardo, Eleonora Cremonini, Anna Górska, Fulvia Mazzaferri, Lorenzo Maria Canziani, Mona Mustafa Hellou, Yudith Olchowski, Itamar Poran, Mariska Leeflang, Jorge Villacian, Herman Goossens, Mical Paul, Evelina Tacconelli
Journal: Clinical Microbiology and Infection (2021)

Point-of-care tests could be essential in differentiating bacterial and viral acute community-acquired lower respiratory tract infections and driving antibiotic stewardship in the community.To assess diagnostic test accuracy of point-of-care tests in community settings for acute community-acquired lower respiratory tract infections.Multiple databases (MEDLINE, EMBASE, Web of Science, Cochrane Library, Open Gray) from inception to 31 May 2021, without language restrictions.Diagnostic test accuracy studies involving patients at primary care, outpatient clinic, emergency department and long-term care facilities with a clinical suspicion of acute community-acquired lower respiratory tract infections. The comparator was any test used as a comparison to the index test. In order not to limit the study inclusion, the comparator was not defined a priori.Four investigators independently extracted data, rated risk of bias, and assessed the quality using QUADAS-2.The measures of diagnostic test accuracy were calculated with 95% CI.A total of 421 studies addressed at least one point-of-care test. The diagnostic performance of molecular tests was higher compared with that of rapid diagnostic tests for all the pathogens studied. The accuracy of stand-alone signs and symptoms or biomarkers was poor. Lung ultrasound showed high sensitivity and specificity (90% for both) for the diagnosis of bacterial pneumonia. Rapid antigen-based diagnostic tests for influenza, respiratory syncytial virus, human metapneumovirus, and Streptococcus pneumoniae had sub-optimal sensitivity (range 49%-84%) but high specificity (>80%).Physical examination and host biomarkers are not sufficiently reliable as stand-alone tests to differentiate between bacterial and viral pneumonia. Lung ultrasound shows higher accuracy than chest X-ray for bacterial pneumonia at emergency department. Rapid antigen-based diagnostic tests cannot be considered fully reliable because of high false-negative rates. Overall, molecular tests for all the pathogens considered were found to be the most accurate.
1569P A multicenter analysis of the outcome of cancer patients with neutropenia and COVID-19 infection optionally treated with granulocyte colony-stimulating factor (G-CSF): A comparative analysis
Authors: M. Sereno Moyano, G. Colmenarejo, J. Baena, C. Aguado de la Rosa, X. Mielgo, A. Pertejo, R. Alvarez Alvarez, A. Sánchez, J.L. López, R. Molina, A. Lopez-Alfonso, B. Hernandez, L.E. Chiara Velarde, A.M. Martin, A. López Martin, M. Dorta Suarez, A. Collazo, E. Casado, A. Jimenez Gordo
Journal: Annals of Oncology (2021)
888P Clinical predictors for survival with the addition of chemotherapy in patients with recurrent-metastatic squamous cell carcinoma of the head and neck after progression on immune checkpoint inhibitors
Authors: M. Issa, B. Klamer, P. Bhateja, V. Karivedu, G. Laliotis, K. Dibs, N. Mladkova, X. Pan, M. Old, M. Gamez, J. Grecula, S. Jhawar, D. Mitchell, S. Baliga, R. Carrau, J. Rocco, M. Bonomi, D. Blakaj
Journal: Annals of Oncology (2021)
584P Health-related quality of life (HRQoL) in ACIS: A phase III trial of apalutamide with abiraterone acetate and prednisone (APA + AAP) vs AAP in metastatic castration-resistant prostate cancer (mCRPC)
Authors: S.M. Oudard, K.B. Bevans, G. Attard, E. Efstathiou, T.W. Flaig, F.A. Franke, O.B. Goodman, U. De Giorgi, C.M. Pieczonka, K. Yeruva, P. De Porre, S.D. Brookman-May, S. Dibaj, D. Wu, S.D. Mundle, S. McCarthy, T. Steuber, H. Suzuki, D.E. Rathkopf, F. Saad
Journal: Annals of Oncology (2021)
Antibody Responses to <scp>Epstein‐Barr</scp> Virus in the Preclinical Period of Rheumatoid Arthritis Suggest the Presence of Increased Viral Reactivation Cycles
Authors: Sabrina Fechtner, Heather Berens, Elizabeth Bemis, Rachel L. Johnson, Carla J. Guthridge, Nichole E. Carlson, M. Kristen Demoruelle, John B. Harley, Jess D. Edison, Jill A. Norris, William H. Robinson, Kevin D. Deane, Judith A. James, V. Michael Holers
Journal: Arthritis & Rheumatology (2021)

Patients with established rheumatoid arthritis (RA) demonstrate altered immune responses to Epstein-Barr virus (EBV), but the presence and roles of EBV have not been fully explored during the pre-clinical disease period. This study was undertaken to determine if EBV infection, as evidenced by an altered anti-EBV antibody response, either plays an important role in driving the development of RA or is a result of expanded RA-related autoimmunity.A total of 83 subjects with RA according to the 1987 American College of Rheumatology (ACR) criteria and 83 age-, sex-, and race-matched control subjects without RA were included in our study. We collected sera from RA subjects and matched controls during the pre-RA and post-RA diagnosis periods and tested the sera for the presence of 5 anti-EBV antibodies (anti-EBV nuclear antigen 1 IgG isotype, anti-viral capsid antigen [anti-VCA] isotypes IgG and IgA, and anti-early antigen [EA] isotypes IgG and IgA), 7 RA-related autoantibodies (rheumatoid factor measured by nephelometry [RF-Neph] as well as isotype-specific IgA-RF, IgM-RF, and IgG-RF, and anti-cyclic citrullinated peptide [anti-CCP] antibodies, including anti-CCP2, anti-CCP3, and anti-CCP3.1), 22 cytokines/chemokines, 36 individual anti-citrullinated protein antibodies, and IgG-cytomegalovirus (CMV) antibodies. Random forest classification, mixed modeling, and joint mixed modeling were used to determine differences in anti-EBV antibody levels between RA subjects and controls.Random forest analysis identified the presence of preclinical EBV antibodies in the serum that differentiated RA subjects from controls without RA. Specifically, IgG-EA antibody levels were higher in RA subjects (mean ± SD 0.82 ± 0.72 international standardized ratio [ISR]) compared to controls (mean ± SD 0.49 ± 0.28 ISR). In subjects with RA, elevated serum IgG-EA levels in the preclinical period before seroconversion were significantly correlated with increased serum IgM-RF levels (P = 0.007), whereas this correlation was not seen in control subjects without RA (P = 0.15). IgG-CMV antibody levels did not differ between groups.Subjects whose serum IgG-EA antibody levels are elevated in the preclinical period will eventually develop RA, which suggests that EBV reactivation cycles are increased during the preclinical period of RA. A combination of RF and EBV reactivation may play an important role in the development of RA.
Nestin promotes pulmonary fibrosis <i>via</i> facilitating recycling of TGF-β receptor I
Authors: Jiancheng Wang, Xiaofan Lai, Senyu Yao, Hainan Chen, Jianye Cai, Yulong Luo, Yi Wang, Yuan Qiu, Yinong Huang, Xiaoyue Wei, Boyan Wang, Qiying Lu, Yuanjun Guan, Tao Wang, Shiyue Li, Andy Peng Xiang
Journal: European Respiratory Journal (2021)

Idiopathic pulmonary fibrosis (IPF) is a progressive fibrotic lung disease that is characterised by aberrant proliferation of activated myofibroblasts and pathological remodelling of the extracellular matrix. Previous studies have revealed that the intermediate filament protein nestin plays key roles in tissue regeneration and wound healing in different organs. Whether nestin plays a critical role in the pathogenesis of IPF needs to be clarified.Nestin expression in lung tissues from bleomycin-treated mice and IPF patients was determined. Transfection with nestin short hairpin RNA vectors in vitro that regulated transcription growth factor (TGF)-β/Smad signalling was conducted. Biotinylation assays to observe plasma membrane TβRI, TβRI endocytosis and TβRI recycling after nestin knockdown were performed. Adeno-associated virus serotype (AAV)6-mediated nestin knockdown was assessed in vivo.We found that nestin expression was increased in a murine pulmonary fibrosis model and IPF patients, and that the upregulated protein primarily localised in lung α-smooth muscle actin-positive myofibroblasts. Mechanistically, we determined that nestin knockdown inhibited TGF-β signalling by suppressing recycling of TβRI to the cell surface and that Rab11 was required for the ability of nestin to promote TβRI recycling. In vivo, we found that intratracheal administration of AAV6-mediated nestin knockdown significantly alleviated pulmonary fibrosis in multiple experimental mice models.Our findings reveal a pro-fibrotic function of nestin partially through facilitating Rab11-dependent recycling of TβRI and shed new light on pulmonary fibrosis treatment.
Sickle cell disease: first new treatment in two decades becomes available in England
Authors: Jacqui Wise
Journal: BMJ (2021)

The first new treatment for sickle cell disease in 20 years is to become available for patients in England under a managed access agreement, although the National Institute for Health and Care Excellence (NICE) has not yet recommended its routine use in the NHS.1

Crizanlizumab is an intravenous treatment recommended as an option for preventing recurrent sickle cell crisis in people aged 16 or over. It can be taken on its own or alongside hydroxycarbamide.

Amanda Pritchard, NHS chief executive, said the drug …
1497P Cancer patients’ awareness about clinical research: The ELPIS study preliminary results
Authors: C. Cagnazzo, V. Franchina, G. Toscano, F. Fagioli, T. Franchina, G.R.R. Ricciardi, L. Antonuzzo, A. Di Costanzo, A. Russo, S. Cusenza, S. Gori, F. Marchetti, M. Tambaro, P. Piccirillo, O. Nanni, S. Delfanti, M. Di Maio, F. D'Ascanio, V. Adamo
Journal: Annals of Oncology (2021)
72P The association between skeletal muscle measures and chemotherapy-induced toxicity in non-small cell lung cancer patients treated with first-line platinum-based chemotherapy: A prospective follow-up study
Authors: C. de Jong, N. Chargi, G. Herder, S. van Haarlem, F. van der Meer, A.V. Lindert, A. ten Heuvel, J. Brouwer, P. de Jong, L.A. Devriese, A. Huitema, T. Egberts, R. de Bree, V.H. Deneer
Journal: Annals of Oncology (2021)
Progress Toward Poliomyelitis Eradication — Pakistan, January 2020–July 2021
Authors: Chukwuma Mbaeyi, Shahzad Baig, Zainul Khan, Hamish Young, Millhia Kader, Jaume Jorba, Muhammad Rana Safdar, Hamid Jafari, Richard Franka
Journal: MMWR Morbidity and Mortality Weekly Report (2021)

SIAs are mass house-to-house vaccination campaigns targeting children aged <5 years with OPV, regardless of the child's vaccination history.
994P PCR-based analysis of PD-L1 RNA expression in lung cancer: Comparison with commonly utilized immunohistochemical assays
Authors: E.N. Imyanitov, A. Venina, A.O. Ivantsov, E.S. Kuligina, A. Iyevleva, N. Savelov, G. Raskin, S. Aleksakhina
Journal: Annals of Oncology (2021)
Individual- and Community-Level Factors Associated With Detectable and Elevated Blood Lead Levels in US Children
Authors: Marissa Hauptman, Justin K. Niles, Jeffrey Gudin, Harvey W. Kaufman
Journal: JAMA Pediatrics (2021)

<h3>Importance</h3> No safe level of exposure to lead has been identified. <h3>Objective</h3> To evaluate individual- and community-level factors associated with detectable and elevated blood lead levels (BLLs) in children. <h3>Design, Setting, and Participants</h3> This cross-sectional, retrospective study analyzed deidentified results from blood lead tests performed at a large clinical laboratory from October 1, 2018, to February 29, 2020. Participants were 1 141 441 children younger than 6 years living in all 50 US states and the District of Columbia who underwent blood lead testing during the study period. Children who underwent lead testing of unknown source and those with elevated BLLs who received capillary blood lead testing without confirmatory venous testing were excluded. <h3>Exposures</h3> Individual demographic categories included sex, age, and insurance type; community-level demographic categories included pre-1950s housing, poverty, predominant race and ethnicity, and geographical regions. <h3>Main Outcomes and Measures</h3> Proportions of children with detectable (≥1.0 μg/dL) and elevated (≥5.0 μg/dL) BLLs, by exposure category. <h3>Results</h3> Of the 1 141 441 children (586 703 boys [51.4%]; mean [SD] age, 2.3 [1.4] years) in the study, more than half of the children tested (576 092 [50.5%; 95% CI, 50.4%-50.6%]) had detectable BLLs, and 21 172 children (1.9% [95% CI, 1.8%-1.9%]) had BLLs of 5.0 μg/dL or more. In multivariable analyses, children with public insurance had greater odds of having detectable BLLs (adjusted odds ratio [AOR], 2.01 [95% CI, 1.99-2.04]) and elevated BLLs (AOR, 1.08 [95% CI, 1.04-1.12]). The proportion of children with detectable and elevated BLLs increased significantly for progressive pre-1950s housing and poverty quintiles (<i>P</i> &lt; .001). The odds of detectable BLLs were significantly higher among children in the highest vs lowest quintile of pre-1950s housing (AOR, 1.65 [95% CI, 1.62-1.68]) and of poverty (AOR, 1.89 [95% CI, 1.86-1.93]). A similar association was found for those with elevated BLLs, with an AOR of 3.06 (95% CI, 2.86-3.27) for the highest vs lowest quintile of pre-1950 housing and 1.99 (95% CI, 1.88-2.11) for the highest quintile of poverty. Children residing in zip codes with predominantly Black non-Hispanic and non-Latinx populations had higher odds of detectable BLLs (AOR, 1.13 [95% CI, 1.11-1.15]) but lower odds for elevated BLL (AOR, 0.83 [95% CI, 0.80-0.88]). <h3>Conclusions and Relevance</h3> This study suggests that, despite progress in reducing pediatric lead exposure, substantial individual- and community-level disparities persist.
Dual checkpoint blockade of CD47 and PD-L1 using an affinity-tuned bispecific antibody maximizes antitumor immunity
Authors: Shih-Hsun Chen, Pawel K Dominik, Jessica Stanfield, Sheng Ding, Wenjing Yang, Nadia Kurd, Ryan Llewellyn, Jonathan Heyen, Carole Wang, Zea Melton, Thomas Van Blarcom, Kevin C Lindquist, Javier Chaparro-Riggers, Shahram Salek-Ardakani
Journal: Journal for ImmunoTherapy of Cancer (2021)

Background T cell checkpoint immunotherapies have shown promising results in the clinic, but most patients remain non-responsive. CD47-signal regulatory protein alpha (SIRPα) myeloid checkpoint blockade has shown early clinical activity in hematologic malignancies. However, CD47 expression on peripheral blood limits αCD47 antibody selectivity and thus efficacy in solid tumors. Methods To improve the antibody selectivity and therapeutic window, we developed a novel affinity-tuned bispecific antibody targeting CD47 and programmed death-ligand 1 (PD-L1) to antagonize both innate and adaptive immune checkpoint pathways. This PD-L1-targeted CD47 bispecific antibody was designed with potent affinity for PD-L1 and moderate affinity for CD47 to achieve preferential binding on tumor and myeloid cells expressing PD-L1 in the tumor microenvironment (TME). Results The antibody design reduced binding on red blood cells and enhanced selectivity to the TME, improving the therapeutic window compared with αCD47 and its combination with αPD-L1 in syngeneic tumor models. Mechanistically, both myeloid and T cells were activated and contributed to antitumor activity of αCD47/PD-L1 bispecific antibody. Distinct from αCD47 and αPD-L1 monotherapies or combination therapies, single-cell RNA sequencing (scRNA-seq) and gene expression analysis revealed that the bispecific treatment resulted in unique innate activation, including pattern recognition receptor-mediated induction of type I interferon pathways and antigen presentation in dendritic cells and macrophage populations. Furthermore, treatment increased the Tcf7 + stem-like progenitor CD8 T cell population in the TME and promoted its differentiation to an effector-like state. Consistent with mouse data, the compounds were well tolerated and demonstrated robust myeloid and T cell activation in non-human primates (NHPs). Notably, RNA-seq analysis in NHPs provided evidence that the innate activation was mainly contributed by CD47-SIRPα but not PD-L1-PD-1 blockade from the bispecific antibody. Conclusion These findings provide novel mechanistic insights into how myeloid and T cells can be uniquely modulated by the dual innate and adaptive checkpoint antibody and demonstrate its potential in clinical development ( NCT04881045 ) to improve patient outcomes over current PD-(L)1 and CD47-targeted therapies.
VAPIng into ARDS: Acute Respiratory Distress Syndrome and Cardiopulmonary Failure
Authors: Mark A. Sussman
Journal: Pharmacology & Therapeutics (2021)

"Modern" vaping involving battery-operated electronic devices began approximately one dozen years and has quickly evolved into a multibillion dollar industry providing products to an estimated 50 million users worldwide. Originally developed as an alternative to traditional cigarette smoking, vaping now appeals to a diverse demographic including substantial involvement of young people who often have never used cigarettes. The rapid rise of vaping fueled by multiple factors has understandably outpaced understanding of biological effects, made even more challenging due to wide ranging individual user habits and preferences. Consequently while vaping-related research gathers momentum, vaping-associated pathological injury (VAPI) has been established by clinical case reports with severe cases manifesting as acute respiratory distress syndrome (ARDS) with examples of right ventricular cardiac failure. Therefore, basic scientific studies are desperately needed to understand the impact of vaping upon the lungs as well as cardiopulmonary structure and function. Experimental models that capture fundamental characteristics of vaping-induced ARDS are essential to study pathogenesis and formulate recommendations to mitigate harmful effects attributable to ingredients or equipment. So too, treatment strategies to promote recovery from vaping-associated damage require development and testing at the preclinical level. This review summarizes the back story of vaping leading to present day conundrums with particular emphasis upon VAPI-associated ARDS and prioritization of research goals.
2021 update of the EULAR points to consider on the use of immunomodulatory therapies in COVID-19
Authors: Alessia Alunno, Aurélie Najm, Pedro M Machado, Heidi Bertheussen, Gerd-Rüdiger R Burmester, Francesco Carubbi, Gabriele De Marco, Roberto Giacomelli, Olivier Hermine, John D Isaacs, Isabelle Koné-Paut, César Magro-Checa, Iain B McInnes, Pier Luigi Meroni, Luca Quartuccio, A V Ramanan, Manuel Ramos-Casals, Javier Rodríguez Carrio, Hendrik Schulze-Koops, Tanja A Stamm, Sander W Tas, Benjamin Terrier, Dennis G McGonagle, Xavier Mariette
Journal: Annals of the Rheumatic Diseases (2021)

Objectives To update the EULAR points to consider (PtCs) on the use of immunomodulatory therapies in COVID-19. Methods According to the EULAR standardised operating procedures, a systematic literature review up to 14 July 2021 was conducted and followed by a consensus meeting of an international multidisciplinary task force. The new statements were consolidated by formal voting. Results We updated 2 overarching principles and 12 PtC. Evidence was only available in moderate to severe and critical patients. Glucocorticoids alone or in combination with tocilizumab are beneficial in COVID-19 cases requiring oxygen therapy and in critical COVID-19. Use of Janus kinase inhibitors (baricitinib and tofacitinib) is promising in the same populations of severe and critical COVID-19. Anti-SARS-CoV-2 monoclonal antibodies and convalescent plasma may find application in early phases of the disease and in selected subgroups of immunosuppressed patients. There was insufficient robust evidence for the efficacy of other immunomodulators with further work being needed in relation to biomarker-based stratification for IL-1 therapy Conclusions Growing evidence supports incremental efficacy of glucocorticoids alone or combined with tocilizumab/Janus kinase inhibitors in moderate to severe and critical COVID-19. Ongoing studies may unmask the potential application of other therapeutic approaches. Involvement of rheumatologists, as systemic inflammatory diseases experts, should be encouraged in clinical trials of immunomodulatory therapy in COVID-19.
Treatments for poorly controlled asthma
Authors: Orla O’Carroll, Cormac McCarthy, Marcus W Butler
Journal: BMJ (2021)

### What you need to know

A 35 year old man with a prior diagnosis of mild asthma presents to his general practitioner with a three month history of intermittently waking at night with cough and shortness of breath. He works as a chef and has found it difficult to complete a full shift during this time. He has been prescribed beclometasone 200 μg twice a day for a long time and asks if there is a need to change his treatment in light of his new persistent symptoms. 

Poorly controlled or moderate asthma occurs when patients experience either daily symptoms of asthma, nocturnal awakenings, more than two exacerbations per year, or some limitation of their daily activities.12 With frequent alterations of guidelines, and continual development of new medications and delivery devices, choosing a suitable treatment strategy can pose a challenge in clinical practice. In this article, we present the latest guidance on drugs used in primary care for poorly controlled asthma in adults.

### ICS/LABA combination

Inhaled corticosteroids (ICS, eg, beclometasone dipropionate, budesonide, fluticasone furoate, etc) and long acting β agonists (LABA, eg, formoterol, salmeterol, vilanterol, etc) are the mainstay of treatment for poorly controlled or moderate asthma (table 1). ICS suppress airway inflammation leading to reduced bronchial hyperresponsiveness. LABAs act on …
Obesity and hyperinsulinemia drive adipocytes to activate a cell cycle program and senesce
Authors: Qian Li, Carolina E. Hagberg, Helena Silva Cascales, Shuai Lang, Mervi T. Hyvönen, Firoozeh Salehzadeh, Ping Chen, Ida Alexandersson, Eleni Terezaki, Matthew J. Harms, Maria Kutschke, Nahida Arifen, Niels Krämer, Myriam Aouadi, Carole Knibbe, Jeremie Boucher, Anders Thorell, Kirsty L. Spalding
Journal: Nature Medicine (2021)
78P Prognostic value of thyroid transcription factor-1 expression in lung adenocarcinoma in patients treated with anti PD-1/PD-L1
Authors: L. Galland, J. Lecuelle, A.L. Lepage, F. Bibeau, V. Derangere, C. Truntzer, F. Ghiringhelli
Journal: Annals of Oncology (2021)