tbuckley/cabot-search huggingface dataset:
In COPD, prophylactic macrolides, but not tetracyclines or quinolones, reduce exacerbations, with fewer serious adverse events
Authors: Sandra G. Adams, Jay I. Peters
Journal: Annals of Internal Medicine (2021)

Janjua S, Mathioudakis AG, Fortescue R, et al. Prophylactic antibiotics for adults with chronic obstructive pulmonary disease: a network meta-analysis. Cochrane Database Syst Rev. 2021;1:CD013198. 33448349.
Omentin attenuates angiotensin II-induced abdominal aortic aneurysm formation in apolipoprotein E-knockout mice
Authors: Lixin Fang, Koji Ohashi, Naoya Otaka, Hayato Ogawa, Mizuho Hiramatsu-Ito, Hiroshi Kawanishi, Yasuko K Bando, Rei Shibata, Yuuki Shimizu, Katsuhiro Kato, Tomonobu Takikawa, Yuta Ozaki, Mikito Takefuji, Toyoaki Murohara, Noriyuki Ouchi
Journal: Cardiovascular Research (2021)

Abdominal aortic aneurysm (AAA) is an increasing and life-threatening disease. Obesity contributes to an increased risk of AAA. Omentin is a circulating adipokine, which is downregulated in obese complications. Here, we examined whether omentin could modulate angiotensin (Ang) II-induced AAA formation in apolipoprotein E-knockout (apoE-KO) mice.apoE-KO mice were crossed with transgenic mice expressing the human omentin gene in fat tissue (OMT-Tg mice) to generate apoE-KO/OMT-Tg mice. apoE-KO/OMT-Tg and apoE-KO mice were subjected to continuous Ang II infusion by using osmotic mini pumps. apoE-KO/OMT-Tg mice exhibited a lower incidence of AAA formation and a reduced maximal diameter of AAA compared with apoE-KO mice. apoE-KO/OMT-Tg mice showed attenuated disruption of medial elastic fibres in response to Ang II compared with apoE-KO mice. apoE-KO/OMT-Tg mice also displayed reduced expression levels of matrix metalloproteinase (MMP) 9, MMP2, and pro-inflammatory genes in aortic walls compared with apoE-KO mice. Furthermore, systemic administration of omentin also attenuated AAA formation and disruption of medial elastic fibres in response to Ang II in apoE-KO mice. Treatment of human monocyte-derived macrophages with omentin protein attenuated expression of MMP9 and pro-inflammatory mediators, and MMP9 activation after stimulation with lipopolysaccharide. Treatment of human vascular smooth muscle cells (VSMCs) with omentin protein reduced expression and activation of MMP2 after stimulation with tumour necrosis factor α. Omentin treatment increased phosphorylation levels of Akt in human macrophages and VSMCs. The suppressive effects of omentin on MMP9 and MMP2 expression were reversed by inhibition of integrin-αVβ3/PI3-kinase/Akt signalling in macrophages and VSMCs, respectively.These data suggest that omentin acts as an adipokine that can attenuate Ang II-induced development of AAA through suppression of MMP9 and MMP2 expression and inflammatory response in the vascular wall.
Lockdown as a last resort option in case of COVID-19 epidemic rebound: a modelling study
Authors: Cécile Tran Kiem, Pascal Crépey, Paolo Bosetti, Daniel Levy Bruhl, Yazdan Yazdanpanah, Henrik Salje, Pierre-Yves Boëlle, Simon Cauchemez
Journal: Eurosurveillance (2021)

Background Given its high economic and societal cost, policymakers might be reluctant to implement a large-scale lockdown in case of coronavirus disease (COVID-19) epidemic rebound. They may consider it as a last resort option if alternative control measures fail to reduce transmission. Aim We developed a modelling framework to ascertain the use of lockdown to ensure intensive care unit (ICU) capacity does not exceed a peak target defined by policymakers. Methods We used a deterministic compartmental model describing transmission of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and the trajectories of COVID-19 patients in healthcare settings, accounting for age-specific mixing patterns and an increasing probability of severe outcomes with age. The framework is illustrated in the context of metropolitan France. Results The daily incidence of ICU admissions and the number of occupied ICU beds are the most robust indicators to decide when a lockdown should be triggered. When the doubling time of hospitalisations estimated before lockdown is between 8 and 20 days, lockdown should be enforced when ICU admissions reach 3.0–3.7 and 7.8–9.5 per million for peak targets of 62 and 154 ICU beds per million (4,000 and 10,000 beds for metropolitan France), respectively. When implemented earlier, the lockdown duration required to get back below a desired level is also shorter. Conclusions We provide simple indicators and triggers to decide if and when a last-resort lockdown should be implemented to avoid saturation of ICU. These metrics can support the planning and real-time management of successive COVID-19 pandemic waves.
Rationally Designed, Self‐Assembling, Multifunctional Hydrogel Depot Repairs Severe Spinal Cord Injury
Authors: Jingjia Ye, Shuang Jin, Wanxiong Cai, Xiangfeng Chen, Hanyu Zheng, Tianfang Zhang, Wujie Lu, Xiaojian Li, Chengzhen Liang, Qixin Chen, Yaxian Wang, Xiaosong Gu, Bin Yu, Zuobing Chen, Xuhua Wang
Journal: Advanced Healthcare Materials (2021)

Abstract Following severe spinal cord injury (SCI), dysregulated neuroinflammation causes neuronal and glial apoptosis, resulting in scar and cystic cavity formation during wound healing and ultimately the formation of an atrophic microenvironment that inhibits nerve regrowth. Because of this complex and dynamic pathophysiology, a systemic solution for scar‐ and cavity‐free wound healing with microenvironment remodeling to promote nerve regrowth has rarely been explored. A one‐step solution is proposed through a self‐assembling, multifunctional hydrogel depot that punctually releases the anti‐inflammatory drug methylprednisolone sodium succinate (MPSS) and growth factors (GFs) locally according to pathophysiology to repair severe SCI. Synergistically releasing the anti‐inflammatory drug MPSS and GFs in the hydrogel depot throughout SCI pathophysiology protects spared tissues/axons from secondary injury, promotes scar boundary‐ and cavity‐free wound healing, and results in permissive bridges for remarkable axonal regrowth. Behavioral and electrophysiological studies indicate that remnants of spared axons, not regenerating axons, mediate functional recovery, strongly suggesting that additional interventions are still required to render the rebuilt neuronal circuits functional. These findings pave the way for the development of a systemic solution to treat acute SCI.
POS1043 NETAKIMAB REDUCES PSORIATIC ARTHRITIS ACTIVITY IN PATIENTS WITH OR WITHOUT AXIAL DISEASE: SUBANALYSIS OF THE PATERA STUDY
Authors: T. Korotaeva, I. Gaydukova, V. Mazurov, A. Samtsov, V. Khayrutdinov, A. Bakulev, A. Kundzer, N. Soroka, A. Eremeeva
Journal: Annals of the Rheumatic Diseases (2021)

Background: PATERA is an ongoing phase 3 international double-blind, placebo-controlled clinical study of netakimab (NTK) in psoriatic arthritis (PsA) ( NCT03598751 ). Netakimab (NTK) is an anti-interleukin-17A monoclonal antibody approved for psoriasis, ankylosing spondylitis, PsA in Russia and Belarus. Objectives: A subanalysis was performed to define the impact of NTK on PsA activity depending on the presence of axial disease: a subset of patients with inflammatory back pain (IBP) according to self-reported ASAS IBP criteria, 2009 (IBP(+) was compared to those without IBP (IBP(-)). Methods: 194 eligible adult patients with PsA fulfilling the CASPAR criteria, with inadequate response to csDMARD or one TNFi, were randomly assigned to receive NTK 120mg or placebo at weeks 0,1,2,4,6,8,10,14,18,22. Patients with missing values for categorical variables were considered as non-responders in the analysis. For quantitative variables, missing values were replaced using the multiple imputation method. Results: 97 PsA patients (N=54 IBP(+), N=43 IBP(-)) received NTK. Both subpopulations were comparable in gender, age and PsA activity at baseline. The treatment led to a pronounced decline in PsA activity in both subpopulations, significant differences between arms were observed only in DAPSA remission and very low disease activity (VLDA) at week 24 (Figure 1A). Changes from baseline in DAS28-CRP were consistent between IBP(+) and IBP(-) patients with a rapid decline during the first month with further improvement up to week 24 (Figure 1B). A similar trend was observed PsA-specific composite responder index (PSARC) (data not shown). A comparable percentage of IBP(+) and IBP(-) patients achieved PSARC at each timepoint of evaluation with 87% and 86% of responders respectively at week 24. Conclusion: NTK significantly improved PsA activity regardless of the presence of IBP. Figure 1. PsA activity after 24-week treatment with NTK. (A) Percentage of patients with DAPSA remission (0-4), very low disease activity (VLDA), minimal disease activity (MDA) at week 24; (B) change from baseline in DAS28-CRP Acknowledgements: This study was sponsored by JSC BIOCAD. Disclosure of Interests: Tatiana Korotaeva Speakers bureau: Abbvie, Biocad, Eli Lilly, Johnson &amp; Johnson, Janssen, Novartis, Pfizer, UCB, Inna Gaydukova Speakers bureau: Abbvie, Biocad, Eli Lilly, MSD, Novartis, Pfizer, Sandoz, V Mazurov: None declared, Aleksey Samtsov: None declared, Vladislav Khayrutdinov: None declared, Andrey Bakulev: None declared, Alena Kundzer: None declared, Nikolaj Soroka: None declared, Anna Eremeeva Employee of: Biocad.
POS0441 DEVELOPMENT OF RHEUMATOID ARTHRITIS AMONG ANTI-CITRULLINATED PROTEIN ANTIBODIES POSITIVE ASYMPTOMATIC INDIVIDUALS: A PROSPECTIVE OBSERVATIONAL STUDY
Authors: S. Mizuki, K. Horie, K. Imabayashi, K. Mishima, K. Oryoji
Journal: Annals of the Rheumatic Diseases (2021)

Background: In the idividuals with genetic and enviromental risk factors, immune events at mucosal surfaces occur and may precede systemic autoimmunity. Anti-citrullinated protein antibodies (ACPA) are present in the serum for an average of 3-5 years prior to the onset of rheumatoid arthritis (RA) during an asymptomatic period. In ACPA-positivite individuals, the additional presence of RA-related risk factors appears to add significant power for the development of RA. To date, there have been few reports in which clinical courses of ACPA-positive asymptomatic individuals were investigated prospectively. Objectives: To observe the clinical time course of ACPA-positive healthy population for the development of RA. Methods: Healthy volunteers without joint pain or stiffness, who attended the comprehensive health screening of our hospital, were enrolled in this prospective observational study. The serum ACPA levels were quantified by Ig-G anti-cyclic citrullinated peptide enzyme-linked immunosorbent assay with levels &gt; 4.4 U/mL considered positive. ACPA-positive subjects were followed by rheumatologists of our department clinically or a questionnaire sent by mail for screening to detect arthritis. Results: 5,971 healthy individuals without joint symptons were included. Ninty-two (1.5%) were positive for ACPA. Of these, 19 (20.7%) developed RA and two were suspected as RA by mail questionnaire. Their average age were 58-years, and women were 68%. The average duration between the date of serum sampling and diagnosis was 10.7 months. ACPA-positive individuals who developed to RA had higher serum ACPA and Ig-M rheumatoid factor levels than ACPA-positive individuals who did not (P value by Mann-Whitney U test: 0.002, 0.005, respectively). Conclusion: Among ACPA-positive asymptomatic individuals, 20% developed RA. The higher titer of ACPA and Ig-M rheumatoid factor levels are risk factors for devoloping RA. Disclosure of Interests: None declared
UK still lacks a coherent and clearly articulated covid-19 strategy
Authors: Graham Winyard
Journal: BMJ (2021)

Raffle and Gill shine an uncomfortable light on a major strand of UK government policy-mass screening for asymptomatic SARS-CoV-2 infection. 1Presumably there are convincing counter arguments or we would not be spending so much energy and money pursuing mass screening, but it is hard to identify them.What is fundamentally concerning is that, more than a year into the pandemic, this is but one of many aspects of the government's public health approach that is shrouded in controversy.We still lack a coherent and clearly articulated strategy that is securely based on public health principles and promoted from the heart of government.Instead, public debate is conducted by an assortment of distinguished advisers with different connections to the government's Scientific Advisory Group for Emergencies and its subgroups, "speaking in a personal capacity," whereas the chief medical officer and colleagues' principal roles seem as adjuncts to Downing Street press conferences.There is little reason to believe that the new UK Health Security Agency will fill this gap. 2In the early days, uncertainty and confusion were to be expected.Politicians cannot be controlled by their medical advisers, nor should they be.But even in the extraordinary environment of the Trump White House, Anthony Fauci and the National Institute of Allergy and Infectious Diseases made clear what ought to be done.The UK needs and deserves such evidence based clarity.
Detection of cryptogenic malignancies from metagenomic whole genome sequencing of body fluids
Authors: Wei Gu, Eric Talevich, Elaine Hsu, Zhongxia Qi, Anatoly Urisman, Scot Federman, Allan Gopez, Shaun Arevalo, Marc Gottschall, Linda Liao, Jack Tung, Lei Chen, Harumi Lim, Chandler Ho, Maya Kasowski, Jean Oak, Brittany J. Holmes, Iwei Yeh, Jingwei Yu, Linlin Wang, Steve Miller, Joseph L. DeRisi, Sonam Prakash, Jeff Simko, Charles Y. Chiu
Journal: Genome Medicine (2021)

Metagenomic next-generation sequencing (mNGS) of body fluids is an emerging approach to identify occult pathogens in undiagnosed patients. We hypothesized that metagenomic testing can be simultaneously used to detect malignant neoplasms in addition to infectious pathogens.
An Open-Source, Automated Tumor-Infiltrating Lymphocyte Algorithm for Prognosis in Triple-Negative Breast Cancer
Authors: Yalai Bai, Kimberly Cole, Sandra Martinez-Morilla, Fahad Shabbir Ahmed, Jon Zugazagoitia, Johan Staaf, Ana Bosch, Anna Ehinger, Emma Nimeus, Johan Hartman, Balazs Acs, David L. Rimm
Journal: Clinical Cancer Research (2021)

Abstract Purpose: Although tumor-infiltrating lymphocytes (TIL) assessment has been acknowledged to have both prognostic and predictive importance in triple-negative breast cancer (TNBC), it is subject to inter and intraobserver variability that has prevented widespread adoption. Here we constructed a machine-learning based breast cancer TIL scoring approach and validated its prognostic potential in multiple TNBC cohorts. Experimental Design: Using the QuPath open-source software, we built a neural-network classifier for tumor cells, lymphocytes, fibroblasts, and “other” cells on hematoxylin–eosin (H&amp;E)–stained sections. We analyzed the classifier-derived TIL measurements with five unique constructed TIL variables. A retrospective collection of 171 TNBC cases was used as the discovery set to identify the optimal association of machine-read TIL variables with patient outcome. For validation, we evaluated a retrospective collection of 749 TNBC patients comprised of four independent validation subsets. Results: We found that all five machine TIL variables had significant prognostic association with outcomes (P ≤ 0.01 for all comparisons) but showed cell-specific variation in validation sets. Cox regression analysis demonstrated that all five TIL variables were independently associated with improved overall survival after adjusting for clinicopathologic factors including stage, age, and histologic grade (P ≤ 0.0003 for all analyses). Conclusions: Neural net-driven cell classifier-defined TIL variables were robust and independent prognostic factors in several independent validation cohorts of TNBC patients. These objective, open-source TIL variables are freely available to download and can now be considered for testing in a prospective setting to assess clinical utility. See related commentary by Symmans, p. 5446
OP0113 FEMALE REPRODUCTIVE FACTORS AND RISK OF JOINT REPLACEMENT ARTHROPLASTY OF KNEE AND HIP DUE TO OSTEOARTHRITIS IN POSTMENOPAUSAL WOMEN: A NATIONWIDE COHORT STUDY OF 1.36 MILLION WOMEN
Authors: Y. Eun, J. E. Yoo, K. D. Han, D. H. Kim, J. Lee, D. Y. Lee, D. H. Lee, H. Kim, D. W. Shin
Journal: Annals of the Rheumatic Diseases (2021)

Background: Previous studies on the link between female reproductive factors and osteoarthritis (OA) have shown conflicting results. Objectives: This study attempted to explore the association between reproductive factors and joint replacement arthroplasty of knee (TKRA) and hip (THRA) in a large nationwide population-based cohort of postmenopausal women. Methods: 1,218,257 subjects who participated in national health examination in 2009 were included in the study. The study outcomes is incident THRA or TKRA due to severe hip or knee OA. The association of reproductive factors and THRA or TKRA was evaluated using a multivariate-adjusted proportional hazards model. Results: During the mean follow-up duration of 8.2 years, 1,733 incident THRA cases and 65,108 incident TKRA cases were observed. Later age at menarche (aHR 1.12 in 13-14 years; aHR 1.24 in 15-16 years; aHR 1.32 in ≥ 17 years), longer breastfeeding (aHR 1.24 in &lt; 6 months; aHR 1.24 in 6-12 months; aHR 1.50 in ≥ 12 months), HRT (aHR 1.06 in &lt; 2 years; aHR 1.11 in 2-5 years; aHR 1.21 ≥ 5 years) and OC use (aHR 1.11 in &lt; 1 year; aHR 1.17 ≥ 1 year) was associated with increased risk of TKRA for severe knee OA, while later age at menopause (aHR 0.93 in 45-49 years; aHR 0.89 in 50-54 years), longer reproductive span (aHR 0.91 in 30-34 years; aHR 0.87 in 35-39 years; aHR 0.91 in ≥ 40 years) was associated with decreased risk. With regard to THRA for severe hip OA, later menarche (aHR 1.21 ≥ 17 years), longer breastfeeding (aHR 1.39 in &lt; 6 months; aHR 1.31 in ≥ 12 months), and HRT more than 5 years (aHR 1.49) were associated with higher risk. The association between reproductive factors and severe OA was more pronounced in underweight and younger subjects. Conclusion: Our study found that shorter estrogen exposure was associated with higher risk of joint replacement therapy due to severe OA, and such association was more pronounced in underweight and younger subjects. Disclosure of Interests: None declared
Outbreak of pre- and extensively drug-resistant tuberculosis in northern Italy: urgency of cross-border, multidimensional, surveillance systems
Authors: Simone Villa, Elisa Tagliani, Emanuele Borroni, Paola Francesca Castellotti, Maurizio Ferrarese, Arash Ghodousi, Anna Lamberti, Sabrina Senatore, Marino Faccini, Daniela Maria Cirillo, Luigi Ruffo Codecasa
Journal: European Respiratory Journal (2021)

<b>An outbreak of (pre-)extensively drug-resistant tuberculosis was detected in Northern Italy using whole genome sequencing and epidemiological study. This experience suggests that integrated and cross-border surveillance systems should be urgently employed.</b>https://bit.ly/3wtQkBp
Detection of SARS-CoV-2 RNA using RT-LAMP and molecular beacons
Authors: Scott Sherrill-Mix, Young Hwang, Aoife M. Roche, Abigail Glascock, Susan R. Weiss, Yize Li, Leila Haddad, Peter Deraska, Caitlin Monahan, Andrew Kromer, Jevon Graham-Wooten, Louis J. Taylor, Benjamin S. Abella, Arupa Ganguly, Ronald G. Collman, Gregory D. Van Duyne, Frederic D. Bushman
Journal: Genome biology (2021)

Abstract Background Rapid spread of SARS-CoV-2 has led to a global pandemic, resulting in the need for rapid assays to allow diagnosis and prevention of transmission. Reverse transcription-polymerase chain reaction (RT-PCR) provides a gold standard assay for SARS-CoV-2 RNA, but instrument costs are high and supply chains are potentially fragile, motivating interest in additional assay methods. Reverse transcription and loop-mediated isothermal amplification (RT-LAMP) provides an alternative that uses orthogonal and often less expensive reagents without the need for thermocyclers. The presence of SARS-CoV-2 RNA is typically detected using dyes to report bulk amplification of DNA; however, a common artifact is nonspecific DNA amplification, which complicates detection. Results Here we describe the design and testing of molecular beacons, which allow sequence-specific detection of SARS-CoV-2 genomes with improved discrimination in simple reaction mixtures. To optimize beacons for RT-LAMP, multiple locked nucleic acid monomers were incorporated to elevate melting temperatures. We also show how beacons with different fluorescent labels can allow convenient multiplex detection of several amplicons in “single pot” reactions, including incorporation of a human RNA LAMP-BEAC assay to confirm sample integrity. Comparison of LAMP-BEAC and RT-qPCR on clinical saliva samples showed good concordance between assays. To facilitate implementation, we developed custom polymerases for LAMP-BEAC and inexpensive purification procedures, which also facilitates increasing sensitivity by increasing reaction volumes. Conclusions LAMP-BEAC thus provides an affordable and simple SARS-CoV-2 RNA assay suitable for population screening; implementation of the assay has allowed robust screening of thousands of saliva samples per week.
Subcutaneous Rituximab Given to Patients for Other Indications Than CD20+ B-Cell Lymphoma: A Monocentric Study of 20 Cases
Authors: Pierre Peterlin, Thierry Guillaume, Alice Garnier, Amandine Le Bourgeois, Beatrice Mahe, Viviane Dubruille, Nicolas Blin, Pierre Gallas, Cyrille Touzeau, Thomas Gastinne, Anne Lok, Patrick Thomaré, Cécile Chauvin, Steven Le Gouill, Philippe Moreau, Patrice Chevallier
Journal: Blood (2017)
Corrigendum to “Biodegradable zwitterionic polymer membrane coating endowing nanoparticles with ultra-long circulation and enhanced tumor photothermal therapy”[Biomaterials 231 (2020) 119680]
Authors: Shaojun Peng, Boshu Ouyang, Yongzhi Men, Yang Du, Yongbin Cao, Ruihong Xie, Zhiqing Pang, Shun Shen, Wuli Yang
Journal: Biomaterials (2021)