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- Glasbey, JC, et al.
(författare)
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- 2021
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swepub:Mat__t
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| 5. |
- Bianchini, F, et al.
(författare)
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Human neutralizing antibodies to cold linear epitopes and subdomain 1 of the SARS-CoV-2 spike glycoprotein
- 2023
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Ingår i: Science immunology. - : American Association for the Advancement of Science (AAAS). - 2470-9468. ; 8:81, s. eade0958-
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Tidskriftsartikel (refereegranskat)abstract
- Emergence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants diminishes the efficacy of vaccines and antiviral monoclonal antibodies. Continued development of immunotherapies and vaccine immunogens resilient to viral evolution is therefore necessary. Using coldspot-guided antibody discovery, a screening approach that focuses on portions of the virus spike glycoprotein that are both functionally relevant and averse to change, we identified human neutralizing antibodies to highly conserved viral epitopes. Antibody fp.006 binds the fusion peptide and cross-reacts against coronaviruses of the four genera, including the nine human coronaviruses, through recognition of a conserved motif that includes the S2′ site of proteolytic cleavage. Antibody hr2.016 targets the stem helix and neutralizes SARS-CoV-2 variants. Antibody sd1.040 binds to subdomain 1, synergizes with antibody rbd.042 for neutralization, and, similar to fp.006 and hr2.016, protects mice expressing human angiotensin-converting enzyme 2 against infection when present as a bispecific antibody. Thus, coldspot-guided antibody discovery reveals donor-derived neutralizing antibodies that are cross-reactive with Orthocoronavirinae, including SARS-CoV-2 variants.
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| 6. |
- Bianchini, F, et al.
(författare)
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Human neutralizing antibodies to cold linear epitopes and subdomain 1 of the SARS-CoV-2 spike glycoprotein
- 2023
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Ingår i: Science immunology. - : American Association for the Advancement of Science (AAAS). - 2470-9468. ; 8:81, s. eade0958-
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Tidskriftsartikel (refereegranskat)abstract
- Emergence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants diminishes the efficacy of vaccines and antiviral monoclonal antibodies. Continued development of immunotherapies and vaccine immunogens resilient to viral evolution is therefore necessary. Using coldspot-guided antibody discovery, a screening approach that focuses on portions of the virus spike glycoprotein that are both functionally relevant and averse to change, we identified human neutralizing antibodies to highly conserved viral epitopes. Antibody fp.006 binds the fusion peptide and cross-reacts against coronaviruses of the four genera, including the nine human coronaviruses, through recognition of a conserved motif that includes the S2′ site of proteolytic cleavage. Antibody hr2.016 targets the stem helix and neutralizes SARS-CoV-2 variants. Antibody sd1.040 binds to subdomain 1, synergizes with antibody rbd.042 for neutralization, and, similar to fp.006 and hr2.016, protects mice expressing human angiotensin-converting enzyme 2 against infection when present as a bispecific antibody. Thus, coldspot-guided antibody discovery reveals donor-derived neutralizing antibodies that are cross-reactive with Orthocoronavirinae, including SARS-CoV-2 variants.
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| 7. |
- Bianchini, F, et al.
(författare)
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Human neutralizing antibodies to cold linear epitopes and to subdomain 1 of SARS-CoV-2
- 2022
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Ingår i: bioRxiv : the preprint server for biology. - : Cold Spring Harbor Laboratory.
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Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)abstract
- Emergence of SARS-CoV-2 variants diminishes the efficacy of vaccines and antiviral monoclonal antibodies. Continued development of immunotherapies and vaccine immunogens resilient to viral evolution is therefore necessary. Using coldspot-guided antibody discovery, a screening approach that focuses on portions of the virus spike that are both functionally relevant and averse to change, we identified human neutralizing antibodies to highly conserved viral epitopes. Antibody fp.006 binds the fusion peptide and cross-reacts against coronaviruses of the fourgenera, including the nine human coronaviruses, through recognition of a conserved motif that includes the S2’ site of proteolytic cleavage. Antibody hr2.016 targets the stem helix and neutralizes SARS-CoV-2 variants. Antibody sd1.040 binds to subdomain 1, synergizes with antibody rbd.042 for neutralization and, like fp.006 and hr2.016, protects mice when present as bispecific antibody. Thus, coldspot-guided antibody discovery reveals donor-derived neutralizing antibodies that are cross-reactive withOrthocoronavirinae, including SARS-CoV-2 variants.Broadly cross-reactive antibodies that protect from SARS-CoV-2 variants are revealed by virus coldspot-driven discovery.
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- Colombo, GI, et al.
(författare)
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The Association between HDL-C and Subclinical Atherosclerosis Depends on CETP Plasma Concentration: Insights from the IMPROVE Study
- 2021
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Ingår i: Biomedicines. - : MDPI AG. - 2227-9059. ; 9:3
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Tidskriftsartikel (refereegranskat)abstract
- The impact of cholesteryl ester transfer protein (CETP) on atherosclerosis is highly debated. This study aimed to investigate the associations between plasma CETP or CETP genotypes and carotid intima-media thickness (cIMT) and the influence of high-density lipoprotein cholesterol (HDL-C) on these associations. Plasma CETP and HDL-C concentrations were measured in 552 subjects free of any pharmacological treatment from the IMPROVE cohort, which includes 3711 European subjects at high cardiovascular risk. CETP single-nucleotide polymorphisms (SNPs) and cIMT measures (cIMTmax; cIMTmean–max of bifurcations, common and internal carotids; plaque-free common carotid [PF CC]-IMTmean) were available for the full cohort. In drug-free subjects, plasma CETP correlated with HDL-C levels (r = 0.19, p < 0.0001), but not with cIMT variables. When stratified according to HDL-C quartiles, CETP positively correlated with cIMTmax and cIMTmean–max, but not with PF CC-IMTmean, in the top HDL-C quartile only. Positive associations between the CETP concentration and cIMTmax or cIMTmean–max were found in the top HDL-C quartile, whereas HDL-C levels were negatively correlated with cIMTmax and cIMTmean–max when the CETP concentration was below the median (HDL-C × CETP interaction, p = 0.001 and p = 0.003 for cIMTmax and cIMTmean–max, respectively). In the full cohort, three CETP SNPs (rs34760410, rs12920974, rs12708968) were positively associated with cIMTmax. rs12444708 exhibited a significant interaction with HDL-C levels in the prediction of cIMTmax. In conclusion, a significant interplay was found between plasma CETP and/or CETP genotype and HDL-C in the prediction of carotid plaque thickness, as indexed by cIMTmax. This suggests that the association of HDL-C with carotid atherosclerosis is CETP-dependent.
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- Matias, Marisa, et al.
(författare)
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Profiles of Parental Burnout Around the Globe : Similarities and Differences Across 36 Countries
- 2023
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Ingår i: Cross-cultural research. - 1069-3971 .- 1552-3578. ; 57:5, s. 499-538
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Tidskriftsartikel (refereegranskat)abstract
- Parental burnout (PB) is a pervasive phenomenon. Parenting is embedded in cultural values, and previous research has shown the role of individualism in PB. In this paper, we reanalyze previously collected data to identify profiles based on the four dimensions of PB, and explore whether these profiles vary across countries’ levels of collectivistic-individualistic (COL-IND) values. Our sample comprised 16,885 individuals from 36 countries (73% women; 27% men), and we used a latent profile approach to uncover PB profiles. The findings showed five profiles: Fulfilled, Not in PB, Low risk of PB, High risk of PB and Burned out. The profiles pointed to climbing levels of PB in the total sample and in each of the three country groups (High COL/Low IND, Medium COL-IND, Low COL/High IND). Exploratory analyses revealed that distinct dimensions of PB had the most prominent roles in the climbing pattern, depending on the countries’ levels of COL/IND. In particular, we found contrast to be a hallmark dimension and an indicator of severe burnout for individualistic countries. Contrary to our predictions, emotional distance and saturation did not allow a clear differentiation across collectivistic countries. Our findings support several research avenues regarding PB measurement and intervention.
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| 17. |
- Panneman, Daan M., et al.
(författare)
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Cost-effective sequence analysis of 113 genes in 1,192 probands with retinitis pigmentosa and Leber congenital amaurosis
- 2023
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Ingår i: Frontiers in Cell and Developmental Biology. - : Frontiers Media SA. - 2296-634X. ; 11
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Tidskriftsartikel (refereegranskat)abstract
- Introduction: Retinitis pigmentosa (RP) and Leber congenital amaurosis (LCA) are two groups of inherited retinal diseases (IRDs) where the rod photoreceptors degenerate followed by the cone photoreceptors of the retina. A genetic diagnosis for IRDs is challenging since >280 genes are associated with these conditions. While whole exome sequencing (WES) is commonly used by diagnostic facilities, the costs and required infrastructure prevent its global applicability. Previous studies have shown the cost-effectiveness of sequence analysis using single molecule Molecular Inversion Probes (smMIPs) in a cohort of patients diagnosed with Stargardt disease and other maculopathies. Methods: Here, we introduce a smMIPs panel that targets the exons and splice sites of all currently known genes associated with RP and LCA, the entire RPE65 gene, known causative deep-intronic variants leading to pseudo-exons, and part of the RP17 region associated with autosomal dominant RP, by using a total of 16,812 smMIPs. The RP-LCA smMIPs panel was used to screen 1,192 probands from an international cohort of predominantly RP and LCA cases. Results and discussion: After genetic analysis, a diagnostic yield of 56% was obtained which is on par with results from WES analysis. The effectiveness and the reduced costs compared to WES renders the RP-LCA smMIPs panel a competitive approach to provide IRD patients with a genetic diagnosis, especially in countries with restricted access to genetic testing.
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| 18. |
- Roskam, Isabelle, et al.
(författare)
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Parental Burnout Around the Globe : a 42-Country Study
- 2021
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Ingår i: Affective science. - : Springer Science and Business Media LLC. - 2662-205X .- 2662-2041. ; 2, s. 58-79
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Tidskriftsartikel (refereegranskat)abstract
- High levels of stress in the parenting domain can lead to parental burnout, a condition that has severe consequences for both parents and children. It is not yet clear, however, whether parental burnout varies by culture, and if so, why it might do so. In this study, we examined the prevalence of parental burnout in 42 countries (17,409 parents; 71% mothers; Mage = 39.20) and showed that the prevalence of parental burnout varies dramatically across countries. Analyses of cultural values revealed that individualistic cultures, in particular, displayed a noticeably higher prevalence and mean level of parental burnout. Indeed, individualism plays a larger role in parental burnout than either economic inequalities across countries, or any other individual and family characteristic examined so far, including the number and age of children and the number of hours spent with them. These results suggest that cultural values in Western countries may put parents under heightened levels of stress.Supplementary Information: The online version contains supplementary material available at 10.1007/s42761-020-00028-4.
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| 19. |
- Roskam, Isabelle, et al.
(författare)
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Three reasons why parental burnout is more prevalent in individualistic countries : a mediation study in 36 countries
- 2024
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Ingår i: Social Psychiatry and Psychiatric Epidemiology. - : Springer Nature. - 0933-7954 .- 1433-9285. ; 59, s. 681-694
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Tidskriftsartikel (refereegranskat)abstract
- PurposeThe prevalence of parental burnout, a condition that has severe consequences for both parents and children, varies dramatically across countries and is highest in Western countries characterized by high individualism.MethodIn this study, we examined the mediators of the relationship between individualism measured at the country level and parental burnout measured at the individual level in 36 countries (16,059 parents).ResultsThe results revealed three mediating mechanisms, that is, self-discrepancies between socially prescribed and actual parental selves, high agency and self-directed socialization goals, and low parental task sharing, by which individualism leads to an increased risk of burnout among parents.ConclusionThe results confrm that the three mediators under consideration are all involved, and that mediation was higher for self-discrepancies between socially prescribed and actual parental selves, then parental task sharing, and lastly selfdi-rected socialization goals. The results provide some important indications of how to prevent parental burnout at the societal level in Western countries.
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| 22. |
- Farina, R., et al.
(författare)
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Change in the Gingival Margin Profile After the Single Flap Approach in Periodontal Intraosseous Defects
- 2015
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Ingår i: Journal of Periodontology. - : Wiley. - 0022-3492 .- 1943-3670. ; 86:9, s. 1038-1046
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Tidskriftsartikel (refereegranskat)abstract
- Background: The aim of the present study is to evaluate the association of patient-related and site-specific factors, as well as the adopted treatment modality, with the change in buccal (bREC) and interdental (iREC) gingival recession observed at 6 months after treatment of periodontal intraosseous defects with the single flap approach (SFA). Methods: Sixty-six patients contributing 74 intraosseous defects accessed with a buccal SFA and treated with different modalities were selected retrospectively. A two-level (patient and site) model was constructed, with the 6-month changes in bREC and iREC as the dependent variables. Results: 1) Significant 6-month increases in bREC (-0.6 +/- 0.7 mm) and iREC (-0.9 +/- -1.1 mm) were observed. 2) bREC change was significantly predicted by presurgery interproximal probing depth (PD) and depth of osseous dehiscence at the buccal aspect. 3) iREC change was significantly predicted by presurgery interproximal PD and the treatment modality, with defects treated with SFA in combination with a graft material and a bioactive agent being less prone to iREC increase compared to defects treated with SFA alone. Conclusions: After buccal SFA, greater post-surgery increase in bREC must be expected for deep intraosseous defects associated with a buccal dehiscence. The combination of a graft material and a bioactive agent in adjunct to the SFA may limit the postoperative increase in iREC.
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| 23. |
- Simonelli, A., et al.
(författare)
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Prognostic value of a composite outcome measure for periodontal stability following periodontal regenerative treatment: A retrospective analysis at 4 years
- 2023
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Ingår i: Journal of Periodontology. - 0022-3492. ; 94:9, s. 1090-1099
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Tidskriftsartikel (refereegranskat)abstract
- BackgroundRecently, a composite outcome measure (COM) was proposed to describe the short-term results of periodontal regenerative treatment. The present retrospective study aimed at evaluating the prognostic value of COM on clinical attachment level (CAL) change over a 4-year period of supportive periodontal care (SPC). MethodsSeventy-four intraosseous defects in 59 patients were evaluated at 6 months and 4 years following regenerative treatment. Based on 6-month CAL change and probing depth (PD), defects were classified as: COM1 (CAL gain & GE;3 mm, PD & LE;4 mm); COM2 (CAL gain <3 mm, PD & LE;4 mm); COM3 (CAL gain & GE;3 mm, PD >4 mm); or COM4 (CAL gain <3 mm, PD >4 mm). COM groups were compared for "stability" (i.e., CAL gain, no change in CAL or CAL loss <1 mm) at 4 years. Also, groups were compared for mean change in PD and CAL, need for surgical retreatment, and tooth survival. ResultsAt 4 years, the proportion of stable defects in COM1, COM2, COM3, and COM4 group was 69.2%, 75%, 50%, and 28.6%, respectively, with a substantially higher probability for a defect to show stability for COM1, COM2, and COM3 compared with COM4 (odds ratio 4.6, 9.1, and 2.4, respectively). Although higher prevalence of surgical reinterventions and lower tooth survival were observed in COM4, no significant differences were detected among COM groups. ConclusionsCOM may be of value in predicting CAL change at sites undergoing SPC following periodontal regenerative surgery. Studies on larger cohorts, however, are needed to substantiate the present findings.
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