| 1. |
- Engström, Joakim, et al.
(författare)
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Investigating the adsorption of anisotropic diblock copolymer worms onto planar silica and nanocellulose surfaces using a quartz crystal microbalance
- 2021
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Ingår i: Polymer Chemistry. - : Royal Society of Chemistry (RSC). - 1759-9954 .- 1759-9962. ; 12:42, s. 6088-6100
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Tidskriftsartikel (refereegranskat)abstract
- Electrostatic adsorption of cationic polyelectrolytes onto anionic cellulosic substrates is an attractive route for facile surface modification of biorenewable materials. Recently, attention has focused on adsorbing cationic spherical diblock copolymer nanoparticles onto model cellulose and/or nanocellulosic substrates. Herein, we investigate physical adsorption of highly anisotropic copolymer worms bearing either anionic or cationic charge onto planar silica, cellulose nanocrystal (CNC) or cellulose nanofibril (CNF) surfaces using quartz crystal microbalance with dissipation monitoring. Electrostatic interactions dominate in the case of anionic silica and CNC surfaces because the adsorbed mass of cationic worms was greater than that of anionic worms. However, either anionic or cationic worms could be adsorbed onto in situ generated CNF substrates, suggesting that additional interactions were involved: hydrogen bonding, van der Waals forces, and possibly covalent bond formation. Scanning electron and atomic force microscopy studies of the dried planar substrates after adsorption experiments confirmed the presence of adsorbed copolymer worms. Finally, composite worm/CNF films exhibited restricted swelling behavior when immersed in water compared to reference CNF films, suggesting that the worms reinforce CNF films by acting as a physical crosslinker. This study is the first investigation of the physical adsorption of highly anisotropic diblock copolymer worms onto cellulosic surfaces.
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| 2. |
- Pisano, F., et al.
(författare)
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Risk factors for residual disease at re-TUR in a large cohort of T1G3 patients
- 2021
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Ingår i: Actas Urológicas Españolas. - : ENE EDICIONES SL. - 0210-4806 .- 1699-7980. ; 45:6, s. 473-478
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Tidskriftsartikel (refereegranskat)abstract
- Introduction and objectives: The goals of transurethral resection of a bladder tumor (TUR) are to completely resect the lesions and to make a correct diagnosis in order to adequately stage the patient. It is well known that the presence of detrusor muscle in the specimen is a prerequisite to minimize the risk of under staging. Persistent disease after resection of bladder tumors is not uncommon and is the reason why the European Guidelines recommended a re-TUR for all T1 tumors. It was recently published that when there is muscle in the specimen, re-TUR does not influence progression or cancer specific survival. We present here the patient and tumor factors that may influence the presence of residual disease at re-TUR.Material and methods: In our retrospective cohort of 2451 primary T1G3 patients initially treated with BCG, pathology results for 934 patients (38.1%) who underwent re-TUR are available. 74% had multifocal tumors, 20% of tumors were more than 3 cm in diameter and 26% had concomitant CIS. In this subgroup of patients who underwent re-TUR, there was no residual disease in 267 patients (29%) and residual disease in 667 patients (71%): Ta in 378 (40%) and T1 in 289 (31%) patients. Age, gender, tumor status (primary/recurrent), previous intravesical therapy, tumor size, tumor multi-focality, presence of concomitant CIS, and muscle in the specimen were analyzed in order to evaluate risk factors of residual disease at re-TUR, both in univariate analyses and multivariate logistic regressions.Results: The following were not risk factors for residual disease: age, gender, tumor status and previous intravesical chemotherapy. The following were univariate risk factors for presence of residual disease: no muscle in TUR, multiple tumors, tumors >= 3 cm, and presence of concomitant CIS. Due to the correlation between tumor multi-focality and tumor size, the multivariate model retained either the number of tumors or the tumor diameter (but not both), p < 0.001. The presence of muscle in the specimen was no longer significant, while the presence of CIS only remained significant in the model with tumor size, p < 0.001.Conclusions: The most significant factors for a higher risk of residual disease at re-TUR in T1G3 patients are multifocal tumors and tumors more than 3 cm. Patients with concomitant CIS and those without muscle in the specimen also have a higher risk of residual disease.
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| 3. |
- Pisano, F, et al.
(författare)
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Risk factors for residual disease at re-TUR in a large cohort of T1G3 patients.
- 2021
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Ingår i: Actas urologicas espanolas. - : Elsevier BV. - 2173-5786. ; 45:6, s. 473-478
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Tidskriftsartikel (refereegranskat)abstract
- INTRODUCTION AND OBJECTIVES: The goals of transurethral resection of a bladder tumor (TUR) are to completely resect the lesions and to make a correct diagnosis in order to adequately stage the patient. It is well known that the presence of detrusor muscle in the specimen is a prerequisite to minimize the risk of under staging. Persistent disease after resection of bladder tumors is not uncommon and is the reason why the European Guidelines recommended a re-TUR for all T1 tumors. It was recently published that when there is muscle in the specimen, re-TUR does not influence progression or cancer specific survival. We present here the patient and tumor factors that may influence the presence of residual disease at re-TUR.MATERIAL AND METHODS: In our retrospective cohort of 2451 primary T1G3 patients initially treated with BCG, pathology results for 934 patients (38.1%) who underwent re-TUR are available. 74% had multifocal tumors, 20% of tumors were more than 3 cm in diameter and 26% had concomitant CIS. In this subgroup of patients who underwent re-TUR, there was no residual disease in 267 patients (29%) and residual disease in 667 patients (71%): Ta in 378 (40%) and T1 in 289 (31%) patients. Age, gender, tumor status (primary/recurrent), previous intravesical therapy, tumor size, tumor multi-focality, presence of concomitant CIS, and muscle in the specimen were analyzed in order to evaluate risk factors of residual disease at re-TUR, both in univariate analyses and multivariate logistic regressions.RESULTS: The following were not risk factors for residual disease: age, gender, tumor status and previous intravesical chemotherapy. The following were univariate risk factors for presence of residual disease: no muscle in TUR, multiple tumors, tumors > 3 cm, and presence of concomitant CIS. Due to the correlation between tumor multi-focality and tumor size, the multivariate model retained either the number of tumors or the tumor diameter (but not both), p < 0.001. The presence of muscle in the specimen was no longer significant, while the presence of CIS only remained significant in the model with tumor size, p < 0.001.CONCLUSIONS: The most significant factors for a higher risk of residual disease at re-TUR in T1G3 patients are multifocal tumors and tumors more than 3 cm. Patients with concomitant CIS and those without muscle in the specimen also have a higher risk of residual disease.
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| 4. |
- Ringlander, Johan, et al.
(författare)
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Hepatitis B virus particles in serum contain minus strand DNA and degraded pregenomic RNA of variable and inverse lengths
- 2024
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Ingår i: LIVER INTERNATIONAL. - 1478-3223 .- 1478-3231.
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Tidskriftsartikel (refereegranskat)abstract
- This study utilized digital PCR to quantify HBV RNA and HBV DNA within three regions of the HBV genome. Analysis of 75 serum samples from patients with chronic infection showed that HBV RNA levels were higher in core than in S and X regions (median 7.20 vs. 6.80 and 6.58 log copies/mL; p < .0001), whereas HBV DNA levels showed an inverse gradient (7.71 vs. 7.73 and 7.77 log copies/mL, p < .001). On average 80% of the nucleic acid was DNA by quantification in core. The core DNA/RNA ratio was associated with viral load and genotype. In individual patients, the relations between RNA levels in core, S and X were stable over time (n = 29; p = .006). The results suggest that pregenomic RNA is completely reverse transcribed to minus DNA in approximate to 75% of the virus particles, whereas the remaining 25% contain both RNA and DNA of lengths that reflect variable progress of the polymerase.
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| 5. |
- Ritchie, C., et al.
(författare)
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A systematic review shows minimal evidence for measurement properties of psychological functioning outcomes in whiplash
- 2022
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Ingår i: Journal of Clinical Epidemiology. - : Elsevier Inc.. - 0895-4356 .- 1878-5921. ; 151, s. 29-44
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Tidskriftsartikel (refereegranskat)abstract
- Objectives: The aim of this study was to systematically identify, synthesize, and appraise studies on the measurement properties of patient-reported outcome measures (PROMs) for anxiety, depression, fear of movement, pain catastrophizing, post-traumatic stress, self-efficacy, and stress in people with whiplash-associated disorders (WAD). Study Design and Setting: PsycINFO, MEDLINE, EMBASE, CINAHL, PILOTS, Web of Science, and Scopus were searched (November 9, 2021). Studies evaluating any measurement property of relevant PROMs in WAD were included. Two reviewers independently screened the studies and assessed the measurement properties in accordance with the COSMIN guidelines. Results: Measurement properties of 10 PROMs were evaluated in WAD: Pictorial Fear of Activity Scale-Cervical (PFActS-C), Tampa Scale of Kinesiophobia-11, Pain Catastrophizing Scale (PCS), Pain Self-Efficacy Questionnaire (PSEQ), PSEQ-4 item, PSEQ-2a, PSEQ-2b, Self-Efficacy Scale, Harvard Trauma Questionnaire, and Post-Traumatic Stress Diagnostic Scale. Content validity was not examined in any of these PROMs in whiplash. Moderate- or high-quality evidence showed adequate internal structure for the PSEQ, PCS, and PFActS-C, whereas the original structures of the remaining seven PROMs were not confirmed in whiplash. Conclusion: Until further research on the measurement properties of these PROMs is available, researchers may opt to use the PSEQ, PCS, or PFActS-C if the construct is aligned with research aims. © 2022 Elsevier Inc.
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| 6. |
- Torres-Sangiao, E, et al.
(författare)
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Quantification of Adaptive Immune Responses Against Protein-Binding Interfaces in the Streptococcal M1 Protein
- 2024
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Ingår i: Molecular & Cellular Proteomics. - : Elsevier. - 1535-9476 .- 1535-9484. ; 23:5
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Tidskriftsartikel (refereegranskat)abstract
- Bacterial or viral antigens can contain subdominant protein regions that elicit weak antibody responses upon vaccination or infection although there is accumulating evidence that antibody responses against subdominant regions can enhance the protective immune response. One proposed mechanism for subdominant protein regions is the binding of host proteins that prevent antibody production against epitopes hidden within the protein binding interfaces. Here, we used affinity purification combined with quantitative mass spectrometry (AP-MS) to examine the level of competition between antigen-specific antibodies and host-pathogen protein interaction networks using the M1 protein from Streptococcus pyogenes as a model system. As most humans have circulating antibodies against the M1 protein, we first used AP-MS to show that the M1 protein interspecies protein network formed with human plasma proteins is largely conserved in naïve mice. Immunizing mice with the M1 protein generated a time-dependent increase of anti-M1 antibodies. AP-MS analysis comparing the composition of the M1-plasma protein network from naïve and immunized mice showed significant enrichment of 292 IgG peptides associated with 56 IgG chains in the immune mice. Despite the significant increase of bound IgGs, the levels of interacting plasma proteins were not significantly reduced in the immune mice. The results indicate that the antigen-specific polyclonal IgG against the M1 protein primarily targets epitopes outside the other plasma protein binding interfaces. In conclusion, this study demonstrates that AP-MS is a promising strategy to determine the relationship between antigen-specific antibodies and host-pathogen interaction networks that could be used to define subdominant protein regions of relevance for vaccine development.
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| 7. |
- Asem, H., et al.
(författare)
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Functional Nanocarriers for Drug Delivery by Surface Engineering of Polymeric Nanoparticle Post-Polymerization-Induced Self-Assembly
- 2021
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Ingår i: ACS Applied Bio Materials. - : American Chemical Society. - 2576-6422. ; 4:1, s. 1045-1056
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Tidskriftsartikel (refereegranskat)abstract
- Engineered polymeric nanoparticles (NPs) have been comprehensively explored as potential platforms for diagnosis and targeted therapy for several diseases including cancer. Herein, we designed functional poly(acrylic acid)-b-poly(butyl acrylate) (PAA-b-PBA) NPs using reversible addition-fragmentation chain-transfer (RAFT)-mediated emulsion polymerization via polymerization-induced self-assembly (PISA). The hydrophilic PAA-macroRAFT, forming a stabilizing shell (i.e., corona), was chain-extended using the hydrophobic monomer n-butyl acrylate (n-BA), resulting in stable, monodisperse, and reproducible PAA-b-PBA NPs, typically having a diameter of 130 nm. The surface engineering of the PAA-b-PBA NP post-PISA were explored using a two-step approach. The hydrophilic NP-shell corona was modified with allyl groups under mild conditions, using allylamine in water, which resulted in stable allyl-functional NPs (allyl-NPs) suitable for further bioconjugation. The allyl-NPs were subsequently conjugated with a thiol-functional fluorescent dye (BODIPY-SH) to the allyl groups using "thiol-ene"-click chemistry, to mimic the attachment of a thiol-functional target ligand. The successful attachment of BODIPY-SH to the allyl-NPs was corroborated by UV-vis spectroscopy, showing the characteristic absorbance of the BODIPY-fluorophore at 500 nm. Despite modification of NPs with allyl groups and attachment of BODIPY-SH, the NPs retained their colloidal stability and monodispersity as indicated by DLS. This demonstrates that post-PISA functionalization is a robust method for synthesizing functional NPs. Neither the NPs nor allyl-NPs showed significant cytotoxicity toward RAW264.7 or MCF-7 cell lines, which indicates their desirable safety profile. The cellular uptake of the NPs using J774A cells in vitro was found to be time and concentration dependent. The anti-cancer drug doxorubicin was efficiently (90%) encapsulated into the PAA-b-PBA NPs during NP formation. After a small initial burst release during the first 2 h, a controlled release pattern over 7 days was observed. The present investigation demonstrates a potential method for functionalizing polymeric NP post-PISA to produce carriers designed for targeted drug delivery.
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| 8. |
- Bady, Pierre, et al.
(författare)
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DNA methylation-based age acceleration observed in IDH wild-type glioblastoma is associated with better outcome - including in elderly patients
- 2022
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Ingår i: Acta neuropathologica communications. - : BMC. - 2051-5960. ; 10:1
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Tidskriftsartikel (refereegranskat)abstract
- Elderly patients represent a growing proportion of individuals with glioblastoma, who however, are often excluded from clinical trials owing to poor expected prognosis. We aimed at identifying age-related molecular differences that would justify and guide distinct treatment decisions in elderly glioblastoma patients. The combined DNA methylome (450 k) of four IDH wild-type glioblastoma datasets, comprising two clinical trial cohorts, was interrogated for differences based on the patients age, DNA methylation (DNAm) age acceleration (DNAm age "Horvath-clock" minus patient age), DNA methylation-based tumor classification (Heidelberg), entropy, and functional methylation of DNA damage response (DDR) genes. Age dependent methylation included 19 CpGs (p-value <= 0.1, Bonferroni corrected), comprising a CpG located in the ELOVL2 gene that is part of a 13-gene forensic age predictor. Most of the age related CpGs (n = 16) were also associated with age acceleration that itself was associated with a large number of CpGs (n = 50,551). Over 70% age acceleration-associated CpGs (n = 36,348) overlapped with those associated with the DNA methylation based tumor classification (n = 170,759). Gene set enrichment analysis identified associated pathways, providing insights into the biology of DNAm age acceleration and respective commonalities with glioblastoma classification. Functional methylation of several DDR genes, defined as correlation of methylation with gene expression (r <= -0.3), was associated with age acceleration (n = 8), tumor classification (n = 12), or both (n = 4), the latter including MGMT. DNAm age acceleration was significantly associated with better outcome in both clinical trial cohorts, whereof one comprised only elderly patients. Multivariate analysis included treatment (RT, RT/TMZ -> TMZ; TMZ, RT), MGMT promoter methylation status, and interaction with treatment. In conclusion, DNA methylation features of age acceleration are an integrative part of the methylation-based tumor classification (RTK I, RTK II, MES), while patient age seems hardly reflected in the glioblastoma DNA methylome. We found no molecular evidence justifying other treatments in elderly patients, not owing to frailty or co-morbidities.
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| 9. |
- Bernhardson, Britt-Marie, et al.
(författare)
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Sensations, symptoms, and then what? : Early bodily experiences prior to diagnosis of lung cancer
- 2021
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Ingår i: PLOS ONE. - : Public Library of Science. - 1932-6203. ; 16:3
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Tidskriftsartikel (refereegranskat)abstract
- Lung cancer (LC) generally lacks unique core symptoms or signs. However, there are a multitude of bodily sensations that are often non-specific, not easily understood, and many times initially not recognized as indicative of LC by the affected person, which often leads to late diagnosis. In this international qualitative study, we inductively analyzed retrospective accounts of 61 people diagnosed with LC in Denmark, England and Sweden. Using the bodily sensations they most commonly spoke about (tiredness, breathlessness, pain, and cough), we constructed four sensation-based cases to understand the pre-diagnostic processes of reasoning and practice triggered by these key indicators of LC. We thereafter critically applied Hay's model of sensations to symptoms transformation, examining its central concepts of duration, disability and vulnerability, to support understanding of these processes. We found that while duration and disability are clearly relevant, vulnerability is more implicitly expressed in relation to perceived threat. Tiredness, even when of long duration and causing disability, was often related to normal aging, rather than a health threat. Regardless of duration, breathlessness was disturbing and threatening enough to lead to care-seeking. Pain varied by location, duration and degree of disability, and thus also varied in degree of threat perceived. Preconceived, but unmet expectations of what LC-related cough and pain would entail could cause delays by misleading participants; if cough lasted long enough, it could trigger health care contact. Duration, disability, and sense of threat, rather than vulnerability, were found to be relevant concepts for understanding the trajectory to diagnosis for LC among these participants. The process by which an individual, their family and health care providers legitimize sensations, allowing them to be seen as potential symptoms of disease, is also an essential, but varying part of the diagnostic processes described here.
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| 10. |
- Golden, Gregory J, et al.
(författare)
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Endothelial Heparan Sulfate Mediates Hepatic Neutrophil Trafficking and Injury during Staphylococcus aureus Sepsis
- 2021
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Ingår i: mBio. - 2161-2129. ; 12:5
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Tidskriftsartikel (refereegranskat)abstract
- Hepatic failure is an important risk factor for poor outcome in septic patients. Using a chemical tagging workflow and high-resolution mass spectrometry, we demonstrate that rapid proteome remodeling of the vascular surfaces precedes hepatic damage in a murine model of Staphylococcus aureus sepsis. These early changes include vascular deposition of neutrophil-derived proteins, shedding of vascular receptors, and altered levels of heparin/heparan sulfate-binding factors. Modification of endothelial heparan sulfate, a major component of the vascular glycocalyx, diminishes neutrophil trafficking to the liver and reduces hepatic coagulopathy and organ damage during the systemic inflammatory response to infection. Modifying endothelial heparan sulfate likewise reduces neutrophil trafficking in sterile hepatic injury, reflecting a more general role of heparan sulfate contribution to the modulation of leukocyte behavior during inflammation. IMPORTANCE Vascular glycocalyx remodeling is critical to sepsis pathology, but the glycocalyx components that contribute to this process remain poorly characterized. This article shows that during Staphylococcus aureus sepsis, the liver vascular glycocalyx undergoes dramatic changes in protein composition associated with neutrophilic activity and heparin/heparan sulfate binding, all before organ damage is detectable by standard circulating liver damage markers or histology. Targeted manipulation of endothelial heparan sulfate modulates S. aureus sepsis-induced hepatotoxicity by controlling the magnitude of neutrophilic infiltration into the liver in both nonsterile and sterile injury. These data identify an important vascular glycocalyx component that impacts hepatic failure during nonsterile and sterile injury.
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