Conjugation of polyethylene glycols (PEGs) to proteins or drug delivery nanosystems is a widely accepted method to increase the therapeutic index of complex nano-biopharmaceuticals. Nevertheless, ...these drugs and agents are often immunogenic, triggering the rise of anti-drug antibodies (ADAs). Among these ADAs, anti-PEG IgG and IgM were shown to account for efficacy loss due to accelerated blood clearance of the drug (ABC phenomenon) and hypersensitivity reactions (HSRs) entailing severe allergic symptoms with occasionally fatal anaphylaxis. In addition to recapitulating the basic information on PEG and its applications, this review expands on the physicochemical factors influencing its immunogenicity, the prevalence, features, mechanism of formation and detection of anti-PEG IgG and IgM and the mechanisms by which these antibodies (Abs) induce ABC and HSRs. In particular, we highlight the in vitro, animal and human data attesting to anti-PEG Ab-induced complement (C) activation as common underlying cause of both adverse effects. A main message is that correct measurement of anti-PEG Abs and individual proneness for C activation might predict the rise of adverse immune reactions to PEGylated drugs and thereby increase their efficacy and safety.
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We investigate the location of an ultra-hard X-ray selected sample of active galactic nuclei (AGN) from the Swift Burst Alert Telescope (BAT) catalogue with respect to the main sequence (MS) of ...star-forming galaxies using Herschel-based measurements of the star formation rate (SFR) and M
*'s from Sloan Digital Sky Survey photometry where the AGN contribution has been carefully removed. We construct the MS with galaxies from the Herschel Reference Survey and Herschel Stripe 82 Survey using the exact same methods to measure the SFR and M
* as the Swift/BAT AGN. We find that a large fraction of the Swift/BAT AGN lie below the MS indicating decreased specific SFR (sSFR) compared to non-AGN galaxies. The Swift/BAT AGN are then compared to a high-mass galaxy sample (CO Legacy Database for GALEX Arecibo SDSS Survey, COLD GASS), where we find a similarity between the AGN in COLD GASS and the Swift/BAT AGN. Both samples of AGN lie firmly between star-forming galaxies on the MS and quiescent galaxies far below the MS. However, we find no relationship between the X-ray luminosity and distance from the MS. While the morphological distribution of the BAT AGN is more similar to star-forming galaxies, the sSFR of each morphology is more similar to the COLD GASS AGN. The merger fraction in the BAT AGN is much higher than the COLD GASS AGN and star-forming galaxies and is related to distance from the MS. These results support a model in which bright AGN tend to be in high-mass star-forming galaxies in the process of quenching which eventually starves the supermassive black hole itself.
Mondor's disease (MD) is a rare disease that manifests with a palpable cord-like induration on the body surface. In general, MD is a self-limited, benign thrombophlebitis that resolves in four to ...eight weeks without any specific treatment. Cases of MD can be roughly categorized into three different groups based on the site of the lesion as follows: original MD of the anterolateral thoracoabdominal wall, penile MD with dorsum and dorsolateral aspects of the penis, and axillary web syndrome with mid-upper arm after axillary surgery. The diagnosis of MD is rather straightforward and based on a physical examinations. However, some case occur "secondary" with another underlying disease, including malignancy, a hypercoagulative state, and vasculitis. Therefore, it is critical to identify MD precisely, evaluate any possible underlying disease, and avoid any unnecessary invasive tests or treatment. In this paper, we comprehensively review the clinical characteristics of MD.
Improving diagnosis has been one of the most critical issues in medicine for the last two decades. In the context of the rise of digital health and its augmentation and human diagnostic thinking, it ...has become necessary to integrate the concept of digital diagnosis into dual-process theory (DPT), which is the fundamental axis of the diagnostic thinking process physicians. Particularly, since the clinical decision support system (CDSS) corresponds to analytical thinking (system 2) in DPT, it is necessary to redefine system 2 to include the CDSS. However, to the best of my knowledge there has been no concrete conceptual model based on this need. The innovation and novelty of this paper are that it redefines system 2 to include new concepts and shows the relationship among the breakdown of system 2. In this definition, system 2 is divided into "inside" and "outside" brains, where "inside" includes symptomatologic, anatomical, biomechanical-physiological, and etiological thinking approaches, and "outside" includes CDSS. Moreover, this paper discusses the actual and possible future interplay between "inside" and "outside." The author envisions that this paper will serve as a cornerstone for the future development of system 2 diagnostic thinking strategy.
We study the luminosity line ratio in a sample of nearby (z < 0.05) galaxies: 25 star-forming galaxies (SFGs) from the xCOLD GASS survey, 36 hard X-ray-selected active galactic nucleus (AGN) host ...galaxies from the BAT AGN Spectroscopic Survey, and 37 infrared-luminous galaxies from the SCUBA Local Universe Galaxy Survey. We find a trend for r31 to increase with star formation efficiency (SFE). We model r31 using the UCL-PDR code and find that the gas density is the main parameter responsible for the variation of r31, while the interstellar radiation field and cosmic-ray ionization rate play only a minor role. We interpret these results to indicate a relation between SFE and gas density. We do not find a difference in the r31 value of SFGs and AGN host galaxies, when the galaxies are matched in SSFR (〈r31〉 = 0.52 0.04 for SFGs and 〈r31〉 = 0.53 0.06 for AGN hosts). According to the results of the UCL-PDR models, the X-rays can contribute to the enhancement of the CO line ratio, but only for strong X-ray fluxes and for high gas density (nH > 104 cm−3). We find a mild tightening of the Kennicutt-Schmidt relation when we use the molecular gas mass surface density traced by CO(3-2) (Pearson correlation coefficient R = 0.83), instead of the molecular gas mass surface density traced by CO(1-0) (R = 0.78), but the increase in correlation is not statistically significant (p-value = 0.06). This suggests that the CO(3-2) line can be reliably used to study the relation between SFR and molecular gas for normal SFGs at high redshift and to compare it with studies of low-redshift galaxies, as is common practice.
ABSTRACT
We report on our combined analysis of HST, VLT/MUSE, VLT/SINFONI, and ALMA observations of the local Seyfert 2 galaxy, NGC 5728 to investigate in detail the feeding and feedback of the ...active galactic nucleus (AGN). The data sets simultaneously probe the morphology, excitation, and kinematics of the stars, ionized gas, and molecular gas over a large range of spatial scales (10 pc to 10 kpc). NGC 5728 contains a large stellar bar that is driving gas along prominent dust lanes to the inner 1 kpc where the gas settles into a circumnuclear ring. The ring is strongly star forming and contains a substantial population of young stars as indicated by the lowered stellar velocity dispersion and gas excitation consistent with H ii regions. We model the kinematics of the ring using the velocity field of the CO (2–1) emission and stars and find it is consistent with a rotating disc. The outer regions of the disc, where the dust lanes meet the ring, show signatures of inflow at a rate of 1 M$\odot$ yr−1. Inside the ring, we observe three molecular gas components corresponding to the circular rotation of the outer ring, a warped disc, and the nuclear stellar bar. The AGN is driving an ionized gas outflow that reaches a radius of 250 pc with a mass outflow rate of 0.08 M$\odot$ yr−1 consistent with its luminosity and scaling relations from previous studies. While we observe distinct holes in CO emission which could be signs of molecular gas removal, we find that largely the AGN is not disrupting the structure of the circumnuclear region.
Limited therapeutic efficacy of polyethylene glycol-conjugated (PEGylated) protein drugs has been recently reported in animals and human following repeat injections. Since there are reports that an ...accelerated blood clearance (ABC) phenomenon is caused by repeated injection of PEGylated liposome, there is an assumption that PEGylated proteins lose their long circulating property when they are injected repeatedly due to the induction of anti-PEG antibody. Although induction of anti-PEG antibody by PEGylated protein has been reported, there is little evidence of accelerated blood clearance of PEGylated protein upon repeated injection. Herein, we investigated the blood concentration of PEGylated ovalbumin (PEG-OVA), a model PEGylated protein, upon its repeated injection. A single intravenous administration of PEG-OVA elicited an anti-PEG IgM response but not anti-PEG IgG response, while the administration did not elicit antibody against OVA. At 24 h postinjection of test PEG-OVA, although control mice showed 41.6% dose of PEG-OVA in blood, the mice pretreated with PEG-OVA showed rapid clearance of test PEG-OVA from blood and undetectable level of PEG-OVA. Interestingly, the anti-PEG IgM induced by PEGylated liposome did not affect the blood concentration of subsequent dose of PEG-OVA. Our result suggests that anti-PEG IgM is a major contributor to the accelerated blood clearance of PEG-conjugated protein, but the presence of anti-PEG IgM in blood circulation does not necessarily affect circulating property of entire PEGylated materials.
Emphysematous cystitis (EC) is a rare form of complicated urinary tract infection, its characteristic feature being gas within the bladder wall and lumen. Patients with EC present with variable ...clinical manifestations ranging from asymptomatic to severe sepsis. EC is typically observed in elderly women with severe diabetes mellitus. Escherichia coli and Klebsiella pneumoniae are often isolated from urine cultures. Imaging methods, such as plain conventional abdominal radiography and computed tomography, are pivotal for obtaining a definitive diagnosis of EC. Most cases can be treated with a combination of antibiotics, bladder drainage and glycemic control. EC is potentially life-threatening, with a mortality rate of 7%. Early medical intervention can contribute to achieving a favorable prognosis without the need for surgical intervention. In this review, we provide a comprehensive description of the clinical characteristics of EC.
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