tbuckley/cabot-search huggingface dataset:
Patients use fewer analgesics following supervised exercise therapy and patient education: an observational study of 16 499 patients with knee or hip osteoarthritis
Authors: Jonas Bloch Thorlund, Ewa M Roos, Patricia Goro, Emily Gromelsky Ljungcrantz, Dorte Thalund Grønne, Søren T Skou
Journal: British Journal of Sports Medicine (2020)

To investigate changes in analgesic use before and after supervised exercise therapy and patient education in patients with knee or hip osteoarthritis (OA).We recruited 16 499 of 25 933 eligible patients (64%; mean age 64.9; SD 9.6; 73% women) from the Good Life with osteoArthritis in Denmark (GLA:D) registry. Change in proportions of analgesic users (categorised according to analgesic risk profile; opioids > non-steroidal anti-inflammatory drugs > paracetamol) was assessed from before to after an 8-week supervised exercise therapy and patient education programme targeting knee or hip OA pain and functional limitations.Patients reported 13.2 mm (95% CI 12.8 to 13.6) less pain (visual analogue scale 0-100 mm) at follow-up compared with baseline. The proportion of analgesic users reduced from 62.2% (95% CI 61.5 to 63.0) at baseline to 44.1% (95% CI 43.3 to 44.9) at follow-up (absolute change: 18.1% (95% CI 17.3 to 19.0)). Among patients using analgesics at baseline, 52% changed to a lower risk analgesic or discontinued analgesic use. The proportion of opioid users after the exercise therapy was 2.5% (95% CI 2.1 to 2.9) lower than baseline; this represents a relative reduction of 36%.Among patients with knee or hip OA using analgesics, more than half either discontinued analgesic use or shifted to lower risk analgesics following an 8-week structured exercise therapy and patient education programme (GLA:D). These data encourage randomised controlled trial evaluation of whether supervised exercise therapy, combined with patient education, can reduce analgesic use, including opioids, among patients with knee and hip OA pain.
Deep learning-based triage and analysis of lesion burden for COVID-19: a retrospective study with external validation
Authors: Minghuan Wang, Chen Xia, Lu Huang, Shabei Xu, Chuan Qin, Jun Liu, Ying Cao, Pengxin Yu, Tingting Zhu, Hui Zhu, Chaonan Wu, Rongguo Zhang, Xiangyu Chen, Jianming Wang, Guang Du, Chen Zhang, Shaokang Wang, Kuan Chen, Zheng Liu, Liming Xia, Wei Wang
Journal: The Lancet Digital Health (2020)
Effect of post‐procedural evidence‐based therapy on 2‐year prognosis after transcatheter mitral valve repair
Authors: Magnus J. Hagnäs, Carmelo Grasso, Maria Elena Di Salvo, Andrea Sardone, Paola Rapisarda, Matteo Pelliccia, Francesco Dipasquale, Giuseppe Castania, Sarah Mangiafico, Piera Capranzano, Marco Barbanti, Alessandro Denaro, Salvatore Scandura, Timo Mäkikallio, Davide Capodanno, Corrado Tamburino
Journal: European Journal of Heart Failure (2020)
Reassessing the Ethics of Molecular HIV Surveillance in the Era of Cluster Detection and Response: Toward HIV Data Justice
Authors: Stephen Molldrem, Anthony K J Smith
Journal: The American Journal of Bioethics (2020)

In the United States, clinical HIV data reported to surveillance systems operated by jurisdictional departments of public health are re-used for epidemiology and prevention. In 2018, all jurisdictions began using HIV genetic sequence data from clinical drug resistance tests to identify people living with HIV in "clusters" of others with genetically similar strains. This is called "molecular HIV surveillance" (MHS). In 2019, "cluster detection and response" (CDR) programs that re-use MHS data became the "fourth pillar" of the national HIV strategy. Public health re-uses of HIV data are done without consent and are a source of concern among stakeholders. This article presents three cases that illuminate bioethical challenges associated with re-uses of clinical HIV data for public health. We focus on evidence-base, risk-benefit ratio, determining directionality of HIV transmission, consent, and ethical re-use. The conclusion offers strategies for "HIV data justice." The essay contributes to a "bioethics of the oppressed."
Distinguishing High-Performing Health Systems Using a Composite of Publicly Reported Measures of Ambulatory Care
Authors: Denis Agniel, Amelia Haviland, Paul Shekelle, Adam Scherling, Cheryl L. Damberg
Journal: Annals of Internal Medicine (2020)

Payers and policymakers are rewarding high-performing health care providers on the basis of summaries of overall quality performance, and the methods they use for measuring performance are increasingly important.To develop and evaluate a measure that ranks health care systems by ambulatory care quality.Systems were ranked using a composite model that summarizes individual measures of quality, accounts for their correlation, and does not require health care systems to report every measure. The composite measure's suitability was evaluated by examining whether it captured the quality indicated by component measures (validity), whether differences in rank between health care systems were larger than statistical noise (reliability), and whether year-to-year changes in rank were small (stability).California and Minnesota, 2014 to 2016.55 health care systems.Publicly reported measures of ambulatory care quality.The composite measure was valid in that it was broadly representative of the component measures and was not dominated by any single measure. The measure was reliable because the ranks for 93% of California systems and 80% of Minnesota systems were unlikely to be more than 2 places lower or higher. The measure was stable because fewer than half of systems changed ranks by more than 2 ranks from year to year.The analysis is limited to available measures of ambulatory care quality and includes only 2 states.This composite measure uses publicly reported data to produce valid, reliable, and stable ranks of ambulatory care quality for health care systems in Minnesota and California, and this approach could be used in other applications.Agency for Healthcare Research and Quality.
The global burden of chronic urticaria for the patient and society*
Authors: M. Gonçalo, A. Gimenéz‐Arnau, M. Al‐Ahmad, M. Ben‐Shoshan, J.A. Bernstein, L.F. Ensina, D. Fomina, C.A. Galvàn, K. Godse, C. Grattan, M. Hide, C.H. Katelaris, M. Khoshkhui, E. Kocatürk, K. Kulthanan, I. Medina, I. Nasr, J. Peter, P. Staubach, L. Wang, K. Weller, M. Maurer
Journal: British Journal of Dermatology (2020)

Chronic urticaria (CU) affects about 1% of the world population of all ages, mostly young and middle‐aged women. It usually lasts for several years (> 1 year in 25–75% of patients) and often takes > 1 year before effective management is implemented. It presents as chronic spontaneous urticaria (CSU), chronic inducible urticaria (CIndU) or both in the same person. More than 25% of cases are resistant to H1‐antihistamines, even at higher doses, and third‐ and fourth‐line therapies (omalizumab and ciclosporin) control the disease only in two‐thirds of H1‐antihistamine‐resistant patients. Here we review the impact of CU on different aspects of patients' quality of life and the burden of this chronic disease for the patient and society. CU may have a strong impact on health‐related quality of life (HRQoL), particularly when CSU is associated with angio‐oedema and/or CIndU (Dermatology Life Quality Index > 10 in 30% of patients). Comorbidities, such as anxiety and depression, which are present in more than 30% of patients with CSU, compound HRQoL impairment. Severe pruritus and the unpredictable occurrence of weals and angio‐oedema are responsible for sleep disorders; sexual dysfunction; limitations on daily life, work and sports activities; interfering with life within the family and in society; and patients' performance at school and work (6% absenteeism and 25% presenteeism). Apart from treatment costs, with annual values between 900 and 2400 purchasing power parity dollars (PPP$) in Europe and the USA, CU is associated with a high consumption of medical resources and other indirect costs, which may reach a total annual cost of PPP$ 15 550.
Covid-19: Act now to avoid second lockdown, says Independent SAGE
Authors: Jacqui Wise
Journal: BMJ (2020)

The Independent Scientific Advisory Group for Emergencies has published an emergency 10 point plan to avoid a national lockdown,1 while criticising the government for abdicating its reasonability to provide such a plan.

Many areas of the UK are currently in some form of local lockdown, and the government is considering further national measures as numbers of covid-19 cases continue to rise.

Launching the plan, Stephen Reicher, professor of social psychology at the University of St Andrews, said, “We are in a crisis. Infections are spiking and our testing system is broken. The one thing that is absolutely clear is if we do nothing the pandemic will soon …
Sirtuin 5 promotes arterial thrombosis by blunting the fibrinolytic system
Authors: Luca Liberale, Alexander Akhmedov, Nikolaos I Vlachogiannis, Nicole R Bonetti, Vanasa Nageswaran, Melroy X Miranda, Yustina M Puspitasari, Lena Schwarz, Sarah Costantino, Francesco Paneni, Jürg H Beer, Frank Ruschitzka, Fabrizio Montecucco, Thomas F Lüscher, Kimon Stamatelopoulos, Konstantinos Stellos, Giovanni G Camici
Journal: Cardiovascular Research (2020)

Abstract Aims Arterial thrombosis as a result of plaque rupture or erosion is a key event in acute cardiovascular events. Sirtuin 5 (SIRT5) belongs to the lifespan-regulating sirtuin superfamily and has been implicated in acute ischaemic stroke and cardiac hypertrophy. This project aims at investigating the role of SIRT5 in arterial thrombus formation. Methods and results Sirt5 transgenic (Sirt5Tg/0) and knock-out (Sirt5−/−) mice underwent photochemically induced carotid endothelial injury to trigger arterial thrombosis. Primary human aortic endothelial cells (HAECs) were treated with SIRT5 silencing-RNA (si-SIRT5) as well as peripheral blood mononuclear cells from acute coronary syndrome (ACS) patients and non-ACS controls (case–control study, total n = 171) were used to increase the translational relevance of our data. Compared to wild-type controls, Sirt5Tg/0 mice displayed accelerated arterial thrombus formation following endothelial-specific damage. Conversely, in Sirt5−/− mice, arterial thrombosis was blunted. Platelet function was unaltered, as assessed by ex vivo collagen-induced aggregometry. Similarly, activation of the coagulation cascade as assessed by vascular and plasma tissue factor (TF) and TF pathway inhibitor expression was unaltered. Increased thrombus embolization episodes and circulating D-dimer levels suggested augmented activation of the fibrinolytic system in Sirt5−/− mice. Accordingly, Sirt5−/− mice showed reduced plasma and vascular expression of the fibrinolysis inhibitor plasminogen activator inhibitor (PAI)-1. In HAECs, SIRT5-silencing inhibited PAI-1 gene and protein expression in response to TNF-α. This effect was mediated by increased AMPK activation and reduced phosphorylation of the MAP kinase ERK 1/2, but not JNK and p38 as shown both in vivo and in vitro. Lastly, both PAI-1 and SIRT5 gene expressions are increased in ACS patients compared to non-ACS controls after adjustment for cardiovascular risk factors, while PAI-1 expression increased across tertiles of SIRT5. Conclusion SIRT5 promotes arterial thrombosis by modulating fibrinolysis through endothelial PAI-1 expression. Hence, SIRT5 may be an interesting therapeutic target in the context of atherothrombotic events.
Correspondence on ‘Interleukin-6 receptor blockade with subcutaneous tocilizumab in severe COVID-19 pneumonia and hyperinflammation: case–control study’
Authors: Martin Sebastian Winkler, Peter Korsten, Claudia Binder, Björn Tampe
Journal: Annals of the Rheumatic Diseases (2020)

We read with great interest the recent article by Potere et al using interleukin (IL)-6 receptor blockade with subcutaneous tocilizumab in SARS-CoV-2 COVID-19 pneumonia and hyperinflammatory syndrome.1 A potential preventive or therapeutic effect of certain immunomodulatory therapies in COVID-19 has been hypothesised. Among them, corticosteroids, IL-6 or IL-1 antagonists have been reported and successfully used in severe COVID-19 and associated hyperinflammatory syndromes.1–4 The hyperinflammation observed in adult patients with severe COVID-19 resembles a cytokine release syndrome (CRS) associated with CD4+ and CD8+ T-cell lymphopaenia and increased cytokine levels, including IL-6, correlating with clinical severity.5–9 In contrast to CRS, immune reconstitution inflammatory syndrome (IRIS) is an exaggerated inflammatory response driven by predominant CD4+ T helper cells that have been reported secondary to previous initiation of antiretroviral therapy (ART) when the immune system begins to recover following treatment with ART.10 Since ART for COVID-19 is among the leading drug candidates in this pandemic, a clear sense for associated hyperinflammatory syndromes is required.11 We describe here a case of IRIS …
Noncanonical effector functions of the T-memory–like T-PLL cell are shaped by cooperative TCL1A and TCR signaling
Authors: S. Oberbeck, A. Schrader, K. Warner, D. Jungherz, G. Crispatzu, J. von Jan, M. Chmielewski, A. Ianevski, H. H. Diebner, P. Mayer, A. Kondo Ados, L. Wahnschaffe, T. Braun, T. A. Müller, P. Wagle, A. Bouska, T. Neumann, S. Pützer, L. Varghese, N. Pflug, M. Thelen, J. Makalowski, N. Riet, H. J. M. Göx, G. Rappl, J. Altmüller, M. Kotrová, T. Persigehl, G. Hopfinger, M. L. Hansmann, H. Schlößer, S. Stilgenbauer, J. Dürig, D. Mougiakakos, M. von Bergwelt-Baildon, I. Roeder, S. Hartmann, M. Hallek, R. Moriggl, M. Brüggemann, T. Aittokallio, J. Iqbal, S. Newrzela, H. Abken, M. Herling
Journal: Blood (2020)
18F-Fluciclovine Uptake in a Ureterocele
Authors: Ryan Bitar, Janio Szklaruk, Lucia Martiniova, Amado J. Zurita, Lisly J. Chery, Gregory Ravizzini
Journal: Clinical Nuclear Medicine (2020)

Abstract A 60-year-old man with prostate adenocarcinoma status post radical prostatectomy and bilateral pelvic lymph node dissection referred for restaging 18 F-fluciclovine PET/CT due to rising serum prostate-specific antigen levels (1.1 ng/mL at that time of imaging). PET/CT images were obtained from the proximal thighs to the vertex of the skull approximately 3 to 5 minutes after the IV administration of 347.8 MBq (9.4 mCi) of 18 F-fluciclovine. PET/CT imaging demonstrated a focus of abnormally increased 18 F-fluciclovine uptake at the right ureterovesical junction. Subsequent MRI of the pelvis revealed that this focus corresponded to a benign ureterocele.
Polyphenism of a Novel Trait Integrated Rapidly Evolving Genes into Ancestrally Plastic Networks
Authors: Sofia Casasa, Joseph F Biddle, Georgios D Koutsovoulos, Erik J Ragsdale
Journal: Molecular Biology and Evolution (2020)

Abstract Developmental polyphenism, the ability to switch between phenotypes in response to environmental variation, involves the alternating activation of environmentally sensitive genes. Consequently, to understand how a polyphenic response evolves requires a comparative analysis of the components that make up environmentally sensitive networks. Here, we inferred coexpression networks for a morphological polyphenism, the feeding-structure dimorphism of the nematode Pristionchus pacificus. In this species, individuals produce alternative forms of a novel trait—moveable teeth, which in one morph enable predatory feeding—in response to environmental cues. To identify the origins of polyphenism network components, we independently inferred coexpression modules for more conserved transcriptional responses, including in an ancestrally nonpolyphenic nematode species. Further, through genome-wide analyses of these components across the nematode family (Diplogastridae) in which the polyphenism arose, we reconstructed how network components have changed. To achieve this, we assembled and resolved the phylogenetic context for five genomes of species representing the breadth of Diplogastridae and a hypothesized outgroup. We found that gene networks instructing alternative forms arose from ancestral plastic responses to environment, specifically starvation-induced metabolism and the formation of a conserved diapause (dauer) stage. Moreover, loci from rapidly evolving gene families were integrated into these networks with higher connectivity than throughout the rest of the P. pacificus transcriptome. In summary, we show that the modular regulatory outputs of a polyphenic response evolved through the integration of conserved plastic responses into networks with genes of high evolutionary turnover.
Engineered cell-degradable poly(2-alkyl-2-oxazoline) hydrogel for epicardial placement of mesenchymal stem cells for myocardial repair
Authors: Yaqi You, Kazuya Kobayashi, Burcu Colak, Piaopiao Luo, Edward Cozens, Laura Fields, Ken Suzuki, Julien Gautrot
Journal: Biomaterials (2020)

Epicardial placement of mesenchymal stromal cells (MSCs) is a promising strategy for cardiac repair post-myocardial infarction, but requires the design of biomaterials to maximise the retention of donor cells on the heart surface and control their phenotype. To this end, we propose the use of a poly(2-alkyl-2-oxazoline) (POx) derivative, based on 2-ethyl-2-oxazoline and 2-butenyl-2-oxazoline. This POx polymer can be cured rapidly (less than 2 min) via photo-irradiation due to the use of di-cysteine cell degradable peptides. We report that the cell-degradable properties of the resulting POx hydrogels enables the regulation of cell protrusion in corresponding 3D matrices and that this, in turn, regulates the secretory phenotype of MSCs. In particular, the expression of pro-angiogenic genes was upregulated in partially cell-degradable POx hydrogels. Improved angiogenesis was confirmed in an in vitro microfluidic assay. Finally, we confirmed that, owing to the excellent tissue adhesive properties of thiol-ene crosslinked hydrogels, the epicardial placement of MSC-loaded POx hydrogels promoted the recovery of cardiac function and structure with reduced interstitial fibrosis and improved neovascular formation in a rat myocardial infarction model. This report demonstrates that engineered synthetic hydrogels displaying controlled mechanical, cell degradable and bioactive properties are particularly attractive candidates for the epicardial placement of stem cells to promote cardiac repair post myocardial infarction.
Targeted delivery of miR-99b reprograms tumor-associated macrophage phenotype leading to tumor regression
Authors: Liang Wang, Yi-Yang Hu, Jun-Long Zhao, Fei Huang, Shi-Qian Liang, Lei Dong, Yan Chen, Heng-Chao Yu, Jian Bai, Jia-Meng Yang, Jie-Yi Fan, Lei Feng, San-Zhong Li, Hua Han, Hong-Yan Qin
Journal: Journal for ImmunoTherapy of Cancer (2020)

Background Accumulating evidence has shown that tumor-associated macrophages (TAMs) play a critical role in tumor progression. Targeting TAMs is a potential strategy for tumor immunotherapy. However, the mechanism underlying the TAM phenotype and function needs to be resolved. Our previous studies have demonstrated that miR-125a can reverse the TAM phenotype toward antitumor. Meanwhile, we have found that miR-125a and miR-99b cluster in the first intron of the same host gene, and are transcribed simultaneously in bone marrow-derived macrophages (BMDMs) following LPS+IFNγ stimulation. However, it remains unclear whether miR-99b by itself can exert an antitumor effect by regulating macrophage phenotype. Methods miR-99b and/or miR-125a were delivered into TAMs of orthotopic hepatocellular carcinoma (HCC) or subcutaneous Lewis lung cancer (LLC) mice. The effect of treatment was evaluated by live imaging, TUNEL staining and survival tests. The phenotype of the immune cells was determined by qRT-PCR, ELISA, western blot and FACS. The capability of miR-99b-mediated macrophage phagocytosis and antigen presentation was detected by FACS and immunofluorescence staining. The underlying molecular mechanism was examined by qRT-PCR, reporter assay and western blot, and further verified in the tumor model. The expression of miR-99b and its target genes was determined in TAMs sorted from tumor and adjacent tissues in patients with liver cancer. Results Targeted delivery of miR-99b and/or miR-125a into TAMs significantly impeded the growth of HCC and LLC, especially after miR-99b delivery. More importantly, the delivery of miR-99b re-educated TAM toward antitumor phenotype with enhanced immune surveillance. Further investigation of mechanisms showed that macrophage-specific overexpression of miR-99b promoted M1 while suppressing M2 macrophage polarization by targeting κB-Ras2 and/or mTOR, respectively. miR-99b-overexpressed M1 macrophage was characterized by stronger capability of phagocytosis and antigen presentation. Additionally, delivery of simTOR or siκB-Ras2 into TAMs inhibited miR-99b antagomir-triggered tumor growth. Finally, miR-99b expression was lower in TAMs of patients with liver cancer than that in adjacent tissues, while the expression of κB-Ras2 and mTOR was reversed. Conclusions Our results reveal the mechanism of miR-99b-mediated TAM phenotype, indicating that TAM-targeted delivery of miR-99b is a potential strategy for cancer immunotherapy.
Efficacy and Safety of Tocilizumab for Polyarticular‐Course Juvenile Idiopathic Arthritis in the Open‐Label Two‐Year Extension of a Phase III Trial
Authors: Hermine I. Brunner, Nicolino Ruperto, Zbigniew Zuber, Rubén Cuttica, Vladimir Keltsev, Ricardo M. Xavier, Ruben Burgos‐Vargas, Inmaculada Calvo Penades, Earl D. Silverman, Graciela Espada, Manuel Ferrandiz Zavaler, Yukiko Kimura, Carolina Duarte, Chantal Job‐Deslandre, Rik Joos, Wendy Douglass, Sunethra Wimalasundera, Kamal N. Bharucha, Chris Wells, Daniel J. Lovell, Alberto Martini, Fabrizio de Benedetti
Journal: Arthritis & Rheumatology (2020)

To report the 2-year efficacy and safety of tocilizumab (TCZ) in patients with polyarticular-course juvenile idiopathic arthritis (JIA).Patients ages 2-17 years with active polyarticular-course JIA, in whom treatment with methotrexate was unsuccessful, received 16 weeks of open-label intravenous TCZ in part 1 (once every 4 weeks: 8 mg/kg or 10 mg/kg for body weight [BW] <30 kg; 8 mg/kg for BW ≥30 kg). Assessments were based on the JIA-American College of Rheumatology (ACR) response (defined as percentage of improvement in ≥3 of the 6 JIA core response variables [CRVs]). Patients with at least a JIA-ACR30 response (defined as ≥30% improvement in ≥3 of the 6 JIA CRVs without worsening in >1 of the remaining JIA CRVs by >30%) at week 16 were randomly assigned (1:1) to receive TCZ or placebo in part 2. Patients remained in part 2 until either week 40 or the occurrence of JIA flare. Upon starting part 3, all patients received open-label TCZ. At week 104 of the study, efficacy was assessed using JIA-ACR50/70/90 response rates (defined as 50%, 70%, or 90% improvement, respectively), achievement of inactive disease, and the Juvenile Arthritis Disease Activity Score in 71 joints (JADAS-71). Safety was assessed in the all-exposure population per 100 patient-years of exposure.Overall, 188 patients entered part 1, 166 patients entered part 2, and 160 patients entered part 3. By week 104, among the 188 patients in the modified intent-to-treat group who received TCZ, JIA-ACR50/70/90 response rates were 80.3%/77.1%/59.6%, respectively, the median JADAS-71 score decreased from 3.6 at week 40 to 0.7 at week 104, 51.1% of patients had achieved inactive disease, and 31 of 66 patients who had been receiving glucocorticoids discontinued them. Adverse event (AE) and serious AE rates were 406.5 per 100 patient-years and 11.1 per 100 patient-years, respectively. The infection rate was 151.4 per 100 patient-years, and the serious infection rate was 5.2 per 100 patient-years.Patients treated with TCZ for polyarticular-course JIA showed high-level disease control for up to 2 years. The TCZ safety profile was consistent with that previously reported.