tbuckley/cabot-search huggingface dataset:
Modification of PLGA Scaffold by MSC‐Derived Extracellular Matrix Combats Macrophage Inflammation to Initiate Bone Regeneration via TGF‐<i>β</i>‐Induced Protein
Authors: Moyuan Deng, Jiulin Tan, Chengshen Hu, Tianyong Hou, Wei Peng, Juan Liu, Bo Yu, Qijie Dai, Jiangling Zhou, Yusheng Yang, Rui Dong, Changshun Ruan, Shiwu Dong, Jianzhong Xu
Journal: Advanced Healthcare Materials (2020)

Abstract The immunologic response toward chronic inflammation or bone regeneration via the accumulation of M1 or M2 macrophages after injury could determine the fate of biomaterial. Human umbilical cord mesenchymal stem cells (hUCMSCs) have a pivotal immunomodulatory property on directing macrophage behaviors. Herein, for the first time, 3D‐printed poly(lactide‐ co ‐glycolide) (PLGA) scaffolds modified with hUCMSC‐derived extracellular matrix (PLGA‐ECM) are prepared by a facile tissue engineering technique with physical decellularization and 2.44 ± 0.29 mg cm −3 proteins immobilized on the PLGA‐ECM contain multiple soluble cytokines with a sustainable release profile. The PLGA‐ECM not only attenuates the foreign body response, but also improves bone regeneration by increasing the accumulation of M2 macrophages in an improved heterotopic transplantation model of SCID mice. Furthermore, the PLGA‐ECM scaffolds with the knockdown of transforming growth factor‐ β ‐induced protein (TGF β I/ β ig‐H3) demonstrate that M2 macrophage accumulation improved by the PLGA‐ECM could be attributed to increasing the migration of M2 macrophages and the repolarization of M1 macrophages to M2 phenotype, which are mediated by multiple integrin signaling pathways involving in integrin β 7, integrin α 9, and integrin β 1 in a TGF β I‐dependent manner. This study presents an effective surface modification strategy of polymeric scaffolds to initiate tissue regeneration and combat inflammatory response by increasing M2 macrophage accumulation.
Covid-19: Two antibody tests are “highly specific” but vary in sensitivity, evaluations find
Authors: Elisabeth Mahase
Journal: BMJ (2020)

Covid-19: Two antibody tests are "highly specific" but vary in sensitivity, evaluations find Elisabeth MahaseThe BMJ Two tests for covid-19 antibodies developed by the drug companies Roche and Abbott are "highly specific" but one was found to have lower sensitivity than was previously reported by the company, evaluation by Public Health England has shown.Abbott had reported that its assays had a sensitivity of 100% (the true positive rate) 14 days after symptom onset.However, PHE found that it had a sensitivity of 93.4% at 14 days, respectively.PHE published the reports after experts called for transparency in relation to the evaluation results, so that any claims could be fully scrutinised. 1 Now that the evaluations have been made public, experts have said it is not clear whether these tests are any better than other available antibody tests and emphasised that the evaluations did not meet the standard needed for accreditation.Roche's Anti-SARS-CoV-2 serology assay was tested between 5 and 7 May by the PHE diagnostic support group, 2 which used 93 serum samples from convalescent patients and 472 negative samples.The team reported that all negative samples tested negative, giving a specificity of 100%, while the overall sensitivity was 83.87%, rising to 87.0% at 14 days after onset of symptoms, 87.7% 21 days after, and 100% more than 40 days after.Abbott's SARS-CoV-2 IgG kit was tested between 4 and 7 May, 3 with 96 samples from convalescent patients and 759 negative samples.The assay was found to be 99.63%specific, with a sensitivity of 93.90% at 14 days after symptom onset, dropping to 93.40% at 21 days and 87.5% at 40 days.
How Academic Health Systems Can Move Forward Once COVID-19 Wanes
Authors: Steven D. Shapiro, Paul B. Rothman
Journal: JAMA (2020)

Over the past few months, as the coronavirus disease 2019 (COVID-19) pandemic has spread across the world, academic medical centers have provided indispensable service in caring for patients and advancing science, including launching hundreds of clinical trials and other studies focused on treatments and vaccines.To fully focus on COVID-19, many academic health systems (AHSs), as well as clinicians in other health care settings, have radically transformed their operations.AHSs have created additional critical care and acute care capacity, and redeployed physicians, nurses, and trainees to support the needs of patients.The changes have not been limited to the hospitals.Both clinical and nonclinical staff are working from home; AHSs and other groups have deferred a significant amount of nonurgent care; many, if not most, clinicians have begun using telemedicine widely for nonurgent care; and education has become largely virtual.Under normal circumstances these changes might occur over months, years, or even decades.Instead, they have happened in weeks.As the pandemic begins to show signs of receding, life will slowly return to something closer to its pre-COVID-19 patterns.When this happens, AHSs have an opportunity to be reshaped.
Chaperone-Mediated Autophagy in the Light of Evolution: Insight from Fish
Authors: Laury Lescat, Vincent Véron, Brigitte Mourot, Sandrine Péron, Nathalie Chenais, Karine Dias, Natàlia Riera-Heredia, Florian Beaumatin, Karine Pinel, Muriel Priault, Stéphane Panserat, Bénédicte Salin, Yann Guiguen, Julien Bobe, Amaury Herpin, Iban Seiliez
Journal: Molecular Biology and Evolution (2020)

Chaperone-mediated autophagy (CMA) is a major pathway of lysosomal proteolysis recognized as a key player of the control of numerous cellular functions, and whose defects have been associated with several human pathologies. To date, this cellular function is presumed to be restricted to mammals and birds, due to the absence of an identifiable lysosome-associated membrane protein 2A (LAMP2A), a limiting and essential protein for CMA, in nontetrapod species. However, the recent identification of expressed sequences displaying high homology with mammalian LAMP2A in several fish species challenges that view and suggests that CMA likely appeared earlier during evolution than initially thought. In the present study, we provide a comprehensive picture of the evolutionary history of the LAMP2 gene in vertebrates and demonstrate that LAMP2 indeed appeared at the root of the vertebrate lineage. Using a fibroblast cell line from medaka fish (Oryzias latipes), we further show that the splice variant lamp2a controls, upon long-term starvation, the lysosomal accumulation of a fluorescent reporter commonly used to track CMA in mammalian cells. Finally, to address the physiological role of Lamp2a in fish, we generated knockout medaka for that specific splice variant, and found that these deficient fish exhibit severe alterations in carbohydrate and fat metabolisms, in consistency with existing data in mice deficient for CMA in liver. Altogether, our data provide the first evidence for a CMA-like pathway in fish and bring new perspectives on the use of complementary genetic models, such as zebrafish or medaka, for studying CMA in an evolutionary perspective.
Response to: ‘Risk of systemic lupus erythematosus in patients with idiopathic thrombocytopenic purpura: a need for a more accurate control group?’ by Mertz and Arnaud
Authors: Fang Xiao Zhu, Jing-Yang Huang, Wen Qingqing, James Cheng Chung Wei
Journal: Annals of the Rheumatic Diseases (2020)

We thank Dr Mertz and Arnaud1 for their comments on our recent article in the Annals of the Rheumatic Diseases entitled ‘Risk of systemic lupus erythematosus in patients with idiopathic thrombocytopenic purpura: a population-based cohort study’.2 They raised the question about selection of control group and suggest a control group consisting of patients with other autoimmune diseases, such as autoimmune haemolytic anaemia (AIHA), Evans syndrome and thyroiditis, instead of using a standard control group.

We agree that many immune-mediated diseases or chronic infectious diseases might also be attributed to systemic …
Cessation of Attacks of Auricular Paroxysmal Tachycardia by the Use of Calcium
Authors: Joseph B. Wolffe, Samuel Bellet
Journal: Annals of Internal Medicine (2020)

Excerpt The object of this paper is to report a series of five cases of auricular paroxysmal tachycardia, three of which were successfully arrested by the use of calcium intravenously. In all three...
N‐Terminal PreS1 Sequence Regulates Efficient Infection of Cell‐Culture–Generated Hepatitis B Virus
Authors: Asako Murayama, Norie Yamada, Yoshiki Osaki, Masaaki Shiina, Hussein Hassan Aly, Masashi Iwamoto, Senko Tsukuda, Koichi Watashi, Mami Matsuda, Ryosuke Suzuki, Tomohisa Tanaka, Kohji Moriishi, Tetsuro Suzuki, Hironori Nishitsuji, Masaya Sugiyama, Masashi Mizokami, Kunitada Shimotohno, Takaji Wakita, Masamichi Muramatsu, T. Jake Liang, Takanobu Kato
Journal: Hepatology (2020)

An efficient cell-culture system for hepatitis B virus (HBV) is indispensable for research on viral characteristics and antiviral reagents. Currently, for the HBV infection assay in cell culture, viruses derived from HBV genome-integrated cell lines of HepG2.2.15 or HepAD-38 are commonly used. However, these viruses are not suitable for the evaluation of polymorphism-dependent viral characteristics or resistant mutations against antiviral reagents. HBV obtained by the transient transfection of the ordinary HBV molecular clone has limited infection efficiencies in cell culture.We found that an 11-amino-acid deletion (d11) in the preS1 region enhances the infectivity of cell-culture-generated HBV (HBVcc) to sodium taurocholate cotransporting polypeptide-transduced HepG2 (HepG2/NTCP) cells. Infection of HBVcc derived from a d11-introduced genotype C strain (GTC-d11) was ~10-fold more efficient than infection of wild-type GTC (GTC-wt), and the number of infected cells was comparable between GTC-d11- and HepG2.2.15-derived viruses when inoculated with the same genome equivalents. A time-dependent increase in pregenomic RNA and efficient synthesis of covalently closed circular DNA were detected after infection with the GTC-d11 virus. The involvement of d11 in the HBV large surface protein in the enhanced infectivity was confirmed by an HBV reporter virus and hepatitis D virus infection system. The binding step of the GTC-d11 virus onto the cell surface was responsible for this efficient infection.This system provides a powerful tool for studying the infection and propagation of HBV in cell culture and also for developing the antiviral strategy against HBV infection.
Dilation with rigid dilators as primary treatment of subglottic stenosis in pediatrics
Authors: E.J. Romero Manteola, C. Patiño González, P. Ravetta, V. Defago, C. Tessi
Journal: Pulmonology (2020)

Acquired subglottic stenosis (SGS) occurs in 1-2% of children with a history of intubation. An alternative treatment is endoscopic dilation with rigid dilators.Seventy-four patients with SGS grade I to III were treated between 2003 and 2017. Dilations were performed with Hegar-type rigid dilators every 2-3 weeks.Eighty-two percentage of patients responded to the treatment. 10% presented SGS grade I, 35% grade II and 55% grade III. Previous intubation time in successful cases was 12.4 days and it was 32 days in those that failed (p=0.02). The average number of dilations was 3.23 in the group that responded and 2.98 for those that did not respond (p=0.51). The presence of tracheostomy reduced the effectiveness of the treatment (p=0.002). The average follow-up was 43.5 months.The use of rigid dilators under endoscopic control is an effective minimally invasive method for treating patients with SGS grades I to III. Previous intubation time and the presence of tracheostomy were identified as poor prognostic factors.
83P Impact of treatment duration of extended adjuvant therapy with neratinib in early stage HER2+ HR+ breast cancer after trastuzumab-based therapy on patient outcomes
Authors: M. Martin Jimenez, M.I. Gnant, B. Ejlertsen, J.L. Mansi, M. Ruiz-Borrego, E.H. Jakobsen, C.K. Osborne, R. Birhiray, B. Zhang, A. Wong, B. Moy, F.A. Holmes
Journal: Annals of Oncology (2020)
Effect of Nivolumab vs Bevacizumab in Patients With Recurrent Glioblastoma
Authors: David A. Reardon, Alba A. Brandes, Antonio Omuro, Paul Mulholland, Michael Lim, Antje Wick, Joachim Baehring, Manmeet S. Ahluwalia, Patrick Roth, Oliver Bähr, Surasak Phuphanich, Juan Manuel Sepulveda, Paul De Souza, Solmaz Sahebjam, Michael Carleton, Kay Tatsuoka, Corina Taitt, Ricardo Zwirtes, John Sampson, Michael Weller
Journal: JAMA Oncology (2020)

Clinical outcomes for glioblastoma remain poor. Treatment with immune checkpoint blockade has shown benefits in many cancer types. To our knowledge, data from a randomized phase 3 clinical trial evaluating a programmed death-1 (PD-1) inhibitor therapy for glioblastoma have not been reported.To determine whether single-agent PD-1 blockade with nivolumab improves survival in patients with recurrent glioblastoma compared with bevacizumab.In this open-label, randomized, phase 3 clinical trial, 439 patients with glioblastoma at first recurrence following standard radiation and temozolomide therapy were enrolled, and 369 were randomized. Patients were enrolled between September 2014 and May 2015. The median follow-up was 9.5 months at data cutoff of January 20, 2017. The study included 57 multicenter, multinational clinical sites.Patients were randomized 1:1 to nivolumab 3 mg/kg or bevacizumab 10 mg/kg every 2 weeks until confirmed disease progression, unacceptable toxic effects, or death.The primary end point was overall survival (OS).A total of 369 patients were randomized to nivolumab (n = 184) or bevacizumab (n = 185). The MGMT promoter was methylated in 23.4% (43/184; nivolumab) and 22.7% (42/185; bevacizumab), unmethylated in 32.1% (59/184; nivolumab) and 36.2% (67/185; bevacizumab), and not reported in remaining patients. At median follow-up of 9.5 months, median OS (mOS) was comparable between groups: nivolumab, 9.8 months (95% CI, 8.2-11.8); bevacizumab, 10.0 months (95% CI, 9.0-11.8); HR, 1.04 (95% CI, 0.83-1.30); P = .76. The 12-month OS was 42% in both groups. The objective response rate was higher with bevacizumab (23.1%; 95% CI, 16.7%-30.5%) vs nivolumab (7.8%; 95% CI, 4.1%-13.3%). Grade 3/4 treatment-related adverse events (TRAEs) were similar between groups (nivolumab, 33/182 [18.1%]; bevacizumab, 25/165 [15.2%]), with no unexpected neurological TRAEs or deaths due to TRAEs.Although the primary end point was not met in this randomized clinical trial, mOS was comparable between nivolumab and bevacizumab in the overall patient population with recurrent glioblastoma. The safety profile of nivolumab in patients with glioblastoma was consistent with that in other tumor types.ClinicalTrials.gov Identifier: NCT02017717.
Extrafine triple therapy in patients with asthma and persistent airflow limitation
Authors: Dave Singh, Johann Christian Virchow, Giorgio Walter Canonica, Andrea Vele, Maxim Kots, George Georges, Alberto Papi
Journal: European Respiratory Journal (2020)

<b>These <i>post hoc</i> analyses suggest that extrafine triple therapy with beclometasone dipropionate, formoterol fumarate and glycopyrronium may be particularly beneficial in the phenotype of patients with asthma and persistent airflow limitation</b>https://bit.ly/2y3XsvJ
Abstract 28: Automated Characterization and Quantification of Cardiomyocyte Proliferation and Apoptosis in Post Myocardial Infarction Tissue Images
Authors: Polina Gross, Nicolas Honnorat, Erdem Varol, Markus Wallner, Danielle Trappanese, Thomas Sharp, Timothy Starosta, Jason Duran, Sarah Koller, Christos Davatzikos, Steven Houser
Journal: Circulation Research (2016)

Detection of cardiac cell death and cardiomyocyte (CM) proliferation after ischemic injury often hinges on quantitative image analysis of cardiac histopathology. Currently, the analysis of cardiac images has greatly relied on manual measurements of the number or percentages of apoptotic CM nuclei, as well as newly forming CM nuclei. The current manual methodology for image analysis is a tedious, subjective and inconsistent approach. Nuquantus (Nuclei quantification utility software) is a novel machine learning-based analytical method, which classifies and quantifies CM nuclei in post myocardial infarction (MI) fluorescent images. Nuquantus accelerated the image analysis by 6 fold from 12.6 ± 5.6 minutes per image by manual approach to 2.2 ± 0.9 minutes (mean ± standard deviation). The analysis variability reflected by the inter-observer agreement Fleiss Kappa was improved from 0.511 ± 0.006 to 0.695 ± 0.006 (Fleiss Kappa ± standard error (***P&lt;0.0001). The percentage of proliferating CMs out of all proliferating cell types in the heart was compared between Nuquantus and manual approaches in 1 week post MI mouse heart. CM nuclei positive to 5-ethynyl-2′-deoxyuridine (EdU) and DAPI stainings were determined to undergo DNA synthesis in the following regions: Infarct Area 0.95 ± 0.26% vs. 0.24 ± 0.07%, Border Zone 0.67±0.40% vs. 0.21±0.10%, Remote Zone 1.39±0.80% vs. 1.40±0.60% and sham 3.85±2.56% vs. 1.32±1.32% (mean ± standard error) Nuquantus vs. manual count, respectively (N=4). Nuquantus identified and quantified CM nuclear DNA fragmentation in wild-type mouse hearts stained by TUNEL assay and DAPI. In the TUNEL negative controls, we detected 0% vs. 0.1±0.1% apoptotic CM nuclei, and in the positive TUNEL control 84.77±3.49% vs. 95.64±0.69% apoptotic CM nuclei (mean ± standard error, Nuquantus vs. manual). No statistical significance was detected between the different methods. In summary, Nuquantus provides innovative computerized methodology to reliably analyze cardiac tissue images, significantly facilitates image analysis and minimizes human bias. Moreover, validation of Nuquantus indicates that CM proliferation in the remodeling heart is a very rare event.
Reply: Sperm retrieval rates by micro-TESE versus conventional TESE in men with non-obstructive azoospermia—the assumption of independence in effects sizes might lead to misleading conclusions
Authors: Giovanni Corona, Suks Minhas, Carlo Bettocchi, Csilla Krausz, Alessandro Pizzocaro, Walter Vena, Mario Maggi, Nikolaos Sofikitis
Journal: Human Reproduction Update (2020)
Abstract 12009: Temporal Changes in Left Ventricular Ejection Fraction and Their Prognostic Impacts in Patients With Stage B Heart Failure: Insights From the Chart-2 Study
Authors: Hajime Aoyanagi, Kotaro Nochioka, Yasuhiko Sakata, Masanobu Miura, Takashi Shiroto, Ruri Abe, Shintaro Kasahara, Masayuki Sato, Takahide Fujihashi, Shinsuke Yamanaka, Hideka Hayashi, Koichiro Sugimura, Jun Takahashi, Satoshi Miyata, Hiroaki Shimokawa
Journal: Circulation (2019)

Background: We have recently shown that left ventricular (LV) ejection fraction (LVEF) dynamically changes over time with prognostic impacts in patients with Stage C/D heart failure (HF). However, ...
Response to: ‘Hydroxychloroquine shortages during the COVID-19 pandemic’ by Mendel<i>et al</i>
Authors: Iain McInnes
Journal: Annals of the Rheumatic Diseases (2020)

As the COVID-19 crisis moves to its next phase, from 'acute to chronic' as it were, it is important to note that a variety of immune modifier medicines are now being proposed or actively trialled in pursuit of a novel effective intervention for early through to poor prognosis coronavirus infection.Such imaginative and creative approaches are to be welcomed.Given the current mathematical models of COVID-19 pandemic resolution, it seems that this may be a lengthy scenario.In the meantime, some disease-modifying antirheumatic drugs (DMARD) are being used on a presumptive basis, for understandable compassionate reasons, though not always based on robust medical evidence.One consequence of widespread uptake of DMARD use in COVID-19 is that drug availability may be diminished and thereby hamper the management of existing immune-mediated inflammatory diseases and particularly rheumatic and musculoskeletal diseases (RMDs).Many people with RMDs are reliant on such DMARDs to retain their well-being and loss of therapeutics may lead potentially to flare, and disease progression.Mendel et al provide us with important evidence of hydroxychloroquine shortages in Canada provided via a survey of Canadian rheumatologists. 1 They are to be commended for seeking evidence of the same.This aligns well with numerous similar reports emerging across European countries.The European League Against Rheumatism is committed to ensuring equitable access to the medicines necessary to optimally treat RMDs during the COVID-19 pandemic. 2This is especially the case when as yet, few or no randomised controlled data support the use of immune modifiers in the management of COVID-19.Thus, while we are supportive of high-quality clinical trial medicine and indeed are hopeful that successful outcomes will emerge in pursuit of a solution for COVID-19, we prefer that the use of agents such as hydroxychloroquine is reserved in the context of appropriate trials, be they of controlled or wellannotated cohort design.
Abstract 19818: Local, but Not Systemic, Blockade of Autonomic Nervous System Activity is Antiarrhythmic in the Dog With Dofetilide Induced Torsade de Pointes Arrhythmias
Authors: Valerie Y van Weperen, Alexandre Bossu, Jet D Beekman, Marcel A van der Heyden, Marc A Vos
Journal: Circulation (2017)

Introduction: Improper activity of the autonomic nervous system (ANS) is a potent extracardiac trigger for ventricular arrhythmias. Hypothesis: We compared pharmacological blockade of the ANS to bi...
168P Development of a combined clinical model to predict progression-free survival (PFS) in advanced breast cancer (ABC) treated with CDK4/6 inhibitors (CDK4/6i)
Authors: O. Martínez-Sáez, A. Menichetti, L. Pare Brunet, G. Griguolo, A. Rodriguez Hernandez, T. Pascual, M.V. Dieci, P.F. Conte, C.A. Giorgi, F. Brasó-Maristany, N. Chic, D. Martínez, A. Rodríguez, F. Schettini, B. Conte, M. Vidal, B. Adamo, M. Muñoz, A. Prat, V. Guarneri
Journal: Annals of Oncology (2020)