| 1. |
- Neves, Ana Luisa, et al.
(författare)
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Determinants of the Use of Health and Fitness Mobile Apps by Patients With Asthma : Secondary Analysis of Observational Studies
- 2021
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Ingår i: Journal of Medical Internet Research. - : JMIR Publications. - 1438-8871. ; 23:9
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Tidskriftsartikel (refereegranskat)abstract
- Background: Health and fitness apps have potential benefits to improve self-management and disease control among patients with asthma. However, inconsistent use rates have been reported across studies, regions, and health systems. A better understanding of the characteristics of users and nonusers is critical to design solutions that are effectively integrated in patients' daily lives, and to ensure that these equitably reach out to different groups of patients, thus improving rather than entrenching health inequities. Objective: This study aimed to evaluate the use of general health and fitness apps by patients with asthma and to identify determinants of usage. Methods: A secondary analysis of the INSPIRERS observational studies was conducted using data from face-to-face visits. Patients with a diagnosis of asthma were included between November 2017 and August 2020. Individual-level data were collected, including age, gender, marital status, educational level, health status, presence of anxiety and depression, postcode, socioeconomic level, digital literacy, use of health services, and use of health and fitness apps. Multivariate logistic regression was used to model the probability of being a health and fitness app user. Statistical analysis was performed in R. Results: A total of 526 patients attended a face-to-face visit in the 49 recruiting centers and 514 had complete data. Most participants were <= 40 years old (66.4%), had at least 10 years of education (57.4%), and were in the 3 higher quintiles of the socioeconomic deprivation index (70.1%). The majority reported an overall good health status (visual analogue scale [VAS] score>70 in 93.1%) and the prevalence of anxiety and depression was 34.3% and 11.9%, respectively. The proportion of participants who reported using health and fitness mobile apps was 41.1% (n=211). Multivariate models revealed that single individuals and those with more than 10 years of education are more likely to use health and fitness mobile apps (adjusted odds ratio [aOR] 2.22, 95%CI 1.05-4.75 and aOR 1.95, 95%CI 1.12-3.45, respectively). Higher digital literacy scores were also associated with higher odds of being a user of health and fitness apps, with participants in the second, third, and fourth quartiles reporting aORs of 6.74 (95%CI 2.90-17.40), 10.30 (95%CI 4.28-27.56), and 11.52 (95%CI 4.78-30.87), respectively. Participants with depression symptoms had lower odds of using health and fitness apps (aOR 0.32, 95%CI 0.12-0.83). Conclusions: A better understanding of the barriers and enhancers of app use among patients with lower education, lower digital literacy, or depressive symptoms is key to design tailored interventions to ensure a sustained and equitable use of these technologies. Future studies should also assess users' general health-seeking behavior and their interest and concerns specifically about digital tools. These factors may impact both initial engagement and sustained use.
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| 2. |
- Jacome, Cristina, et al.
(författare)
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Feasibility and Acceptability of an Asthma App to Monitor Medication Adherence : Mixed Methods Study
- 2021
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Ingår i: JMIR mhealth and uhealth. - : JMIR Publications. - 2291-5222. ; 9:5
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Tidskriftsartikel (refereegranskat)abstract
- Background: Poor medication adherence is a major challenge in asthma, and objective assessment of inhaler adherence is needed. The InspirerMundi app aims to monitor adherence while providing a positive experience through gamification and social support. Objective: This study aimed to evaluate the feasibility and acceptability of the InspirerMundi app to monitor medication adherence in adolescents and adults with persistent asthma (treated with daily inhaled medication). Methods: A 1-month mixed method multicenter observational study was conducted in 26 secondary care centers from Portugal and Spain. During an initial face-to-face visit, physicians reported patients' asthma therapeutic plan in a structured questionnaire. During the visits, patients were invited to use the app daily to register their asthma medication intakes. A scheduled intake was considered taken when patients registered the intake (inhaler, blister, or other drug formulation) by using the image-based medication detection tool. At 1 month, patients were interviewed by phone, and app satisfaction was assessed on a 1 (low) to 5 (high) scale. Patients were also asked to point out the most and least preferred app features and make suggestions for future app improvements. Results: A total of 107 patients (median 27 [P25-P75 14-40] years) were invited, 92.5% (99/107) installed the app, and 73.8% (79/107) completed the 1-month interview. Patients interacted with the app a median of 9 (P25-P75 1-24) days. At least one medication was registered in the app by 78% (77/99) of patients. A total of 53% (52/99) of participants registered all prescribed inhalers, and 34% (34/99) registered the complete asthma therapeutic plan. Median medication adherence was 75% (P25-P75 25%-90%) for inhalers and 82% (P25-P75 50%-94%) for other drug formulations. Patients were globally satisfied with the app, with 75% (59/79) scoring >= 4,; adherence monitoring, symptom monitoring, and gamification features being the most highly scored components; and the medication detection tool among the lowest scored. A total of 53% (42/79) of the patients stated that the app had motivated them to improve adherence to inhaled medication and 77% (61/79) would recommend the app to other patients. Patient feedback was reflected in 4 major themes: medication-related features (67/79, 85%), gamification and social network (33/79, 42%), symptom monitoring and physician communication (21/79, 27%), and other aspects (16/79, 20%). Conclusions: The InspirerMundi app was feasible and acceptable to monitor medication adherence in patients with asthma. Based on patient feedback and to increase the registering of medications, the therapeutic plan registration and medication detection tool were redesigned. Our results highlight the importance of patient participation to produce a patient-centered and engaging mHealth asthma app.
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| 3. |
- Jacome, Cristina, et al.
(författare)
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Monitoring Adherence to Asthma Inhalers Using the InspirerMundi App : Analysis of Real-World, Medium-Term Feasibility Studies
- 2021
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Ingår i: Frontiers in Medical Technology. - : Frontiers Media S.A.. - 2673-3129. ; 3
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Tidskriftsartikel (refereegranskat)abstract
- Background: Poor medication adherence is a major challenge in asthma and objective assessment of inhaler adherence is needed. InspirerMundi app aims to monitor inhaler adherence while turning it into a positive experience through gamification and social support.Objective: We assessed the medium-term feasibility of the InspirerMundi app to monitor inhaler adherence in real-world patients with persistent asthma (treated with daily inhaled medication). In addition, we attempted to identify the characteristics of the patients related to higher app use.Methods: Two real-world multicenter observational studies, with one initial face-to-face visit and a 4-month telephone interview, were conducted in 29 secondary care centers from Portugal. During an initial face-to-face visit, patients were invited to use the app daily to register their asthma medication intakes. A scheduled intake was considered taken when patients took a photo of the medication (inhaler, blister, or others) using the image-based medication detection tool. Medication adherence was calculated as the number of doses taken as a percentage of the number scheduled. Interacting with the app =30 days was used as the cut-off for higher app use.Results: A total of 114 patients {median 20 [percentile 25 to percentile 75 (P25-P75) 16-36] years, 62% adults} were invited, 107 (94%) installed the app and 83 (73%) completed the 4-month interview. Patients interacted with the app for a median of 18 [3-45] days, translated on a median use rate of 15 [3-38]%. Median inhaler adherence assessed through the app was 34 [4-73]% when considering all scheduled inhalations for the study period. Inhaler adherence assessed was not significantly correlated with self-reported estimates. Median adherence for oral and other medication was 41 [6-83]% and 43 [3-73]%, respectively. Patients with higher app use were slightly older (p = 0.012), more frequently taking medication for other health conditions (p = 0.040), and more frequently prescribed long-acting muscarinic antagonists (LAMA, p = 0.024). After 4 months, Control of Allergic Rhinitis and Asthma Test (CARAT) scores improved (p < 0.001), but no differences between patients interacting with the app for 30 days or less were seen.Conclusions: The InspirerMundi app was feasible to monitor inhaler adherence in patients with persistent asthma. The persistent use of this mHealth technology varies widely. A better understanding of characteristics related to higher app use is still needed before effectiveness studies are undertaken.
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| 4. |
- Simoes Cunha, Mafalda, et al.
(författare)
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Symptoms of anxiety and depression in patients with persistent asthma : a cross-sectional analysis of the INSPIRERS studies
- 2023
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Ingår i: BMJ Open. - : BMJ Publishing Group Ltd. - 2044-6055. ; 13:5
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Tidskriftsartikel (refereegranskat)abstract
- ObjectivesAnxiety and depression are relevant comorbidities in asthma, but, in Portugal and Spain, data on this topic are scarce. We assessed, in patients with asthma, the frequency of anxiety and depression using the Hospital Anxiety and Depression Scale (HADS) and the European Quality of Life Five Dimension Questionnaire (EQ-5D); the level of agreement between these questionnaires, and the factors associated with these symptoms.MethodsThis is a secondary analysis of the INSPIRERS studies. A total of 614 adolescents and adults with persistent asthma (32.6 +/- 16.9 years, 64.7% female) were recruited from 30 primary care centres and 32 allergy, pulmonology and paediatric clinics. Demographic and clinical characteristics, HADS and EQ-5D were collected. A score >= 8 on Hospital Anxiety and Depression Scale-Anxiety/Hospital Anxiety and Depression Scale-Depression or a positive answer to EQ-5D item 5 indicated the presence of these symptoms. Agreement was determined by Cohen's kappa. Two multivariable logistic regressions were built.ResultsAccording to HADS, 36% of the participants had symptoms of anxiety and 12% of depression. According to EQ-5D, 36% of the participants had anxiety/depression. The agreement between questionnaires in identifying anxiety/depression was moderate (k=0.55, 95% CI 0.48 to 0.62). Late asthma diagnosis, comorbidities and female gender were predictors of anxiety/depression, while better asthma control, health-related quality of life and perception of health were associated with lower odds for anxiety/depression.ConclusionAt least 1/3 of the patients with persistent asthma experience symptoms of anxiety/depression, showing the relevance of screening these disorders in patients with asthma. EQ-5D and HADS questionnaires showed a moderate agreement in the identification of anxiety/depression symptoms. The identified associated factors need to be further investigated in long-term studies.
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| 5. |
- Amaral, Rita, et al.
(författare)
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Profiling Persistent Asthma Phenotypes in Adolescents : A Longitudinal Diagnostic Evaluation from the INSPIRERS Studies
- 2021
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Ingår i: International Journal of Environmental Research and Public Health. - : MDPI. - 1661-7827 .- 1660-4601. ; 18:3
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Tidskriftsartikel (refereegranskat)abstract
- We aimed to identify persistent asthma phenotypes among adolescents and to evaluate longitudinally asthma-related outcomes across phenotypes. Adolescents (13-17 years) from the prospective, observational, and multicenter INSPIRERS studies, conducted in Portugal and Spain, were included (n = 162). Latent class analysis was applied to demographic, environmental, and clinical variables, collected at a baseline medical visit. Longitudinal differences in clinical variables were assessed at a 4-month follow-up telephone contact (n = 128). Three classes/phenotypes of persistent asthma were identified. Adolescents in class 1 (n = 87) were highly symptomatic at baseline and presented the highest number of unscheduled healthcare visits per month and exacerbations per month, both at baseline and follow-up. Class 2 (n = 32) was characterized by female predominance, more frequent obesity, and uncontrolled upper/lower airways symptoms at baseline. At follow-up, there was a significant increase in the proportion of controlled lower airway symptoms (p < 0.001). Class 3 (n = 43) included mostly males with controlled lower airways symptoms; at follow-up, while keeping symptom control, there was a significant increase in exacerbations/month (p = 0.015). We have identified distinct phenotypes of persistent asthma in adolescents with different patterns in longitudinal asthma-related outcomes, supporting the importance of profiling asthma phenotypes in predicting disease outcomes that might inform targeted interventions and reduce future risk.
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| 6. |
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| 7. |
- Marto, João Pedro, et al.
(författare)
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Safety and Outcome of Revascularization Treatment in Patients With Acute Ischemic Stroke and COVID-19: The Global COVID-19 Stroke Registry.
- 2023
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Ingår i: Neurology. - 1526-632X. ; 100:7
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Tidskriftsartikel (refereegranskat)abstract
- COVID-19-related inflammation, endothelial dysfunction, and coagulopathy may increase the bleeding risk and lower the efficacy of revascularization treatments in patients with acute ischemic stroke (AIS). We aimed to evaluate the safety and outcomes of revascularization treatments in patients with AIS and COVID-19.This was a retrospective multicenter cohort study of consecutive patients with AIS receiving intravenous thrombolysis (IVT) and/or endovascular treatment (EVT) between March 2020 and June 2021 tested for severe acute respiratory syndrome coronavirus 2 infection. With a doubly robust model combining propensity score weighting and multivariate regression, we studied the association of COVID-19 with intracranial bleeding complications and clinical outcomes. Subgroup analyses were performed according to treatment groups (IVT-only and EVT).Of a total of 15,128 included patients from 105 centers, 853 (5.6%) were diagnosed with COVID-19; of those, 5,848 (38.7%) patients received IVT-only and 9,280 (61.3%) EVT (with or without IVT). Patients with COVID-19 had a higher rate of symptomatic intracerebral hemorrhage (SICH) (adjusted OR 1.53; 95% CI 1.16-2.01), symptomatic subarachnoid hemorrhage (SSAH) (OR 1.80; 95% CI 1.20-2.69), SICH and/or SSAH combined (OR 1.56; 95% CI 1.23-1.99), 24-hour mortality (OR 2.47; 95% CI 1.58-3.86), and 3-month mortality (OR 1.88; 95% CI 1.52-2.33). Patients with COVID-19 also had an unfavorable shift in the distribution of the modified Rankin score at 3 months (OR 1.42; 95% CI 1.26-1.60).Patients with AIS and COVID-19 showed higher rates of intracranial bleeding complications and worse clinical outcomes after revascularization treatments than contemporaneous non-COVID-19 patients receiving treatment. Current available data do not allow direct conclusions to be drawn on the effectiveness of revascularization treatments in patients with COVID-19 or to establish different treatment recommendations in this subgroup of patients with ischemic stroke. Our findings can be taken into consideration for treatment decisions, patient monitoring, and establishing prognosis.The study was registered under ClinicalTrials.gov identifier NCT04895462.
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| 8. |
- Pocas, Juliana, et al.
(författare)
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Syndecan-4 is a maestro of gastric cancer cell invasion and communication that underscores poor survival
- 2023
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Ingår i: Proceedings of the National Academy of Sciences of the United States of America. - : Proceedings of the National Academy of Sciences (PNAS). - 0027-8424 .- 1091-6490. ; 120:20
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Tidskriftsartikel (refereegranskat)abstract
- Gastric cancer is a dominating cause of cancer-associated mortality with limited therapeutic options. Here, we show that syndecan-4 (SDC4), a transmembrane pro-teoglycan, is highly expressed in intestinal subtype gastric tumors and that this sig -nature associates with patient poor survival. Further, we mechanistically demonstrate that SDC4 is a master regulator of gastric cancer cell motility and invasion. We also find that SDC4 decorated with heparan sulfate is efficiently sorted in extracellular vesicles (EVs). Interestingly, SDC4 in EVs regulates gastric cancer cell-derived EV organ distribution, uptake, and functional effects in recipient cells. Specifically, we show that SDC4 knockout disrupts the tropism of EVs for the common gastric cancer metastatic sites. Our findings set the basis for the molecular implications of SDC4 expression in gastric cancer cells and provide broader perspectives on the development of therapeutic strategies targeting the glycan-EV axis to limit tumor progression.
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| 9. |
- Alves, Rita, et al.
(författare)
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GATA2 at the mitosis-to-G1 transition is critical for definitive hematopoiesis
- 2021
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Ingår i: Experimental Hematology. - : Elsevier BV. - 1873-2399 .- 0301-472X. ; 100:Suppl, s. 35-35
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Konferensbidrag (refereegranskat)abstract
- In mitosis, transcription factors (TFs) and RNA polymerase disperse across the cytoplasm leading to transcriptional silencing, but some TFs are retained on condensed chromatin and mark genomic sites, a mechanism termed mitotic bookmarking. In pluripotent and differentiated cells this mechanism is important for pluripotency maintenance, cell reprogramming and lineage inheritance. However, the role of bookmarking in adult stem cells or in an in vivo system is yet to be addressed. Hematopoietic stem cells undergo drastic changes in cell cycle during development while balancing self-renewal and differentiation, suggesting a possible role for bookmarking.Here, we first addressed the mitotic retention capacity of the hemogenic TFs GATA2, GFI1B and FOS. We show that GATA2 remains bound to chromatin at all phases of cell cycle, as opposed to GFI1B and FOS. The C-terminal zinc finger (C-ZF) and the nuclear localization signal domains are required for GATA2 mitotic binding. Point mutations in the C-ZF associated with leukemia also impact GATA2 retention. To address the role of GATA2-mediated mitotic bookmarking, we have fused GATA2 to a mitosis degradation (MD) domain, which promotes protein destruction at the mitosis-to-G1 transition (M-G1). Degradation of GATA2 at M-G1 impacts the reprogramming of human fibroblasts to hemogenic cells. To address the role of GATA2 at M-G1 in vivo, we have generated a mouse model with the MD domain inserted upstream the Gata2 gene. Remarkably, homozygous mice are lethal, phenocopying Gata2 null mice which die at the onset of definitive hematopoiesis, showing a deficit in hematopoietic stem and progenitor cells.These findings implicate GATA2 as a mitotic bookmarking factor and its critical role at M-G1 for definitive hematopoiesis. Overall, our study highlights a dependency on mitotic bookmarkers for in vivo lineage commitment.
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| 10. |
- Anjos, Rita, et al.
(författare)
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Macular Ganglion Cell Layer and Peripapillary Retinal Nerve Fibre Layer Thickness in Patients with Unilateral Posterior Cerebral Artery Ischaemic Lesion : An Optical Coherence Tomography Study
- 2016
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Ingår i: Neuro-ophthalmology (Aeolus Press. 1980). - : Taylor & Francis. - 0165-8107 .- 1744-506X. ; 40:1, s. 8-15
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Tidskriftsartikel (refereegranskat)abstract
- The purpose of this study is to evaluate the macular ganglion cell layer (GCL) and peripapillary retinal nerve fibre layer (RNFL) thickness in patients with unilateral posterior cerebral artery (PCA) ischaemic lesions using spectral-domain optical coherence tomography (SD-OCT). A prospective, case-control study of patients with unilateral PCA lesion was conducted in the neuro-ophthalmology clinic of Centro Hospitalar Lisboa Central. Macular and peripapillary SD-OCT scans were performed in both eyes of each patient. Twelve patients with PCA lesions (stroke group) and 12 healthy normal controls were included in this study. Peripapillary RNFL comparison between both eyes of the same subject in the stroke group found a thinning in the superior-temporal (p = 0.008) and inferior-temporal (p = 0.023) sectors of the ipsilateral eye and nasal sector (p = 0.003) of the contralateral eye. Macular GCL thickness comparison showed a reduction temporally in the ipsilateral eye (p = 0.004) and nasally in the contralateral eye (p = 0.002). Peripapillary RNFL thickness was significantly reduced in both eyes of patients with PCA compared with controls, affecting all sectors in the contralateral eye and predominantly temporal sectors in the ipsilateral eye. A statistically significant decrease in macular GCL thickness was found in both hemiretinas of both eyes of stroke patients when compared with controls (p < 0.05). This study shows that TRD may play a role in the physiopathology of lesions of the posterior visual pathway.
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| 11. |
- Ascic, Ervin, et al.
(författare)
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Harnessing Dendritic Cell Reprogramming to Elucidate Mechanisms of Tumor Immunity
- 2022
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Konferensbidrag (övrigt vetenskapligt/konstnärligt)abstract
- The presence of conventional dendritic cells type 1 (cDC1) in the tumor correlates with positive treatment outcome. The ability to cross-present neoantigens and prime protective CD8+ T-cell responses, makes cDC1s central for tumor immunity. However, in tumors cDC1 are rare and often functionally impaired. Our group reported that overexpression of the transcription factors PU.1, IRF8 and BATF3 (PIB) converts mouse and human fibroblasts into cross-presenting cDC1-like cells. We employed the minimal gene regulatory network of highly immunogenic cDC1 and restored the immunogenicity of low immunogenic lung cancer and melanoma cell lines by reprogramming into professional tumor antigen presenting cells (tumor-APCs). Here, we report that upon transduction with PIB, 23 solid syngeneic cancer lines initiate reprogramming into cDC1-like cells expressing CD45 and MHC-II at efficiencies ranging from 0.5-57.7%. Functionally, PIB overexpression endows tumor cells with the capacity to cross-present exogenous antigen and prime naïve CD8+ T-cells. Adoptive transfer of ovalbumin cross-presenting B16 tumor-APCs into established ovalbumin expressing B16 tumors (B16-OVA) elicits tumor growth control and extends animal survival. Treated animals show a systemic antigen-specific T cell response against ovalbumin and endogenous tumor-associated antigen MuLV p15E. Intratumoral injection of reprogrammed B2905 and LLC into tumors shows differential response, correlating with their cross-presentation capacity. This approach combines cDC1 antigen cross-presentation abilities with the generation of tumor antigens. The induction of a cDC1 identity in tumor cells sets in motion T cell responses in vitro and in vivo. In the future of this project, dendritic cell reprogramming will be object in a 2-cell CRISPR/Cas9 screen using induced cDC1-like tumor cells and reporter T-cells to explore mechanistically cross-presentation regulators. The generation of cross-presenting tumor-APCs will be also used to map and characterize presented and cross-presented neoantigens. Finally, dendritic cell reprogramming of tumor cells will be explored in vivo by replenishing cDC1 within the tumor microenvironment through in vivo reprogramming. Ultimately, this project will provide insight into mechanisms of cross-presentation and pave the way for the development of novel cDC1-centric therapies.
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| 12. |
- de Souza, Itamara Parente, et al.
(författare)
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Seasonal precipitation variability modes over South America associated to El Niño-Southern Oscillation (ENSO) and non-ENSO components during the 1951–2016 period
- 2021
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Ingår i: International Journal of Climatology. - : Wiley. - 0899-8418 .- 1097-0088. ; 41:8, s. 4321-4338
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Tidskriftsartikel (refereegranskat)abstract
- Anomalous seasonal patterns of precipitation variability over South America (SA) associated with El Niño-Southern Oscillation (ENSO) and non-ENSO (residual) conditions were assessed during 1951–2016. Patterns were obtained from empirical orthogonal functions analysis of total and residual precipitation seasonal anomalies. In austral spring and summer, precipitation variability is dominated by a dipolar anomaly mode with a centre extending from northwestern to northeastern SA and another in central-eastern Brazil and part of southeastern SA (SESA) during spring, and a centre in northwestern SA and another extending from northeastern SA to central and eastern Brazil and central SESA, during summer. These modes are associated with ENSO to a greater extent during spring than summer. In summer, there is a strong association of the dipolar precipitation pattern with sea surface temperature (SST) anomalies on the east coast of Brazil, which indicates local influence. In austral fall, SST anomalies in the tropical South Atlantic relate to precipitation anomalies in northeast SA, and those in the tropical north Atlantic (TNA) to precipitation anomalies in northwestern SA, through the intertropical convergence zone anomalous position modulated by SST anomalies. In this same condition, the ENSO acts only to intensify or weaken the dominant precipitation pattern, depending on its phase, mainly over SESA. In contrast, the second variability mode in fall is characterized by positive SST anomalies in the Indian Ocean and equatorial and southern Atlantic Ocean and negative in the TNA. The importance of ENSO and the Indian Ocean in the characterization of the SST dipole in the tropical Atlantic explains the main changes in precipitation patterns over northeastern Brazil not been discussed in previous studies.
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| 13. |
- Dias, N., et al.
(författare)
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Outcomes of Elective and Non-elective Fenestrated-branched Endovascular Aortic Repair for Treatment of Thoracoabdominal Aortic Aneurysms
- 2023
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Ingår i: Annals of Surgery. - : Lippincott Williams & Wilkins. - 0003-4932 .- 1528-1140. ; 278:4, s. 568-577, s. 568-577
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Tidskriftsartikel (refereegranskat)abstract
- Objective: To describe outcomes after elective and non-elective fenestrated-branched endovascular aortic repair (FB-EVAR) for thoracoabdominal aortic aneurysms (TAAAs).Background: FB-EVAR has been increasingly utilized to treat TAAAs; however, outcomes after non-elective versus elective repair are not well described.Methods: Clinical data of consecutive patients undergoing FB-EVAR for TAAAs at 24 centers (2006-2021) were reviewed. Endpoints including early mortality and major adverse events (MAEs), all-cause mortality, and aortic-related mortality (ARM), were analyzed and compared in patients who had non-elective versus elective repair.Results: A total of 2603 patients (69% males; mean age 72 +/- 10 year old) underwent FB-EVAR for TAAAs. Elective repair was performed in 2187 patients (84%) and non-elective repair in 416 patients [16%; 268 (64%) symptomatic, 148 (36%) ruptured]. Non-elective FB-EVAR was associated with higher early mortality (17% vs 5%, P < 0.001) and rates of MAEs (34% vs 20%, P < 0.001). Median follow-up was 15 months ( interquartile range, 7-37 months). Survival and cumulative incidence of ARM at 3 years were both lower for non-elective versus elective patients (50 +/- 4% vs 70 +/- 1% and 21 +/- 3% vs 7 +/- 1%, P < 0.001). On multivariable analysis, non-elective repair was associated with increased risk of all-cause mortality ( hazard ratio, 1.92; 95% CI] 1.50-2.44; P < 0.001) and ARM (hazard ratio, 2.43; 95% CI, 1.63-3.62; P < 0.001).Conclusions: Non-elective FB-EVAR of symptomatic or ruptured TAAAs is feasible, but carries higher incidence of early MAEs and increased all-cause mortality and ARM than elective repair. Long-term follow-up is warranted to justify the treatment.
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| 14. |
- Dias-Neto, Marina, et al.
(författare)
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Comparison of single- and multistage strategies during fenestrated-branched endovascular aortic repair of thoracoabdominal aortic aneurysms
- 2023
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Ingår i: Journal of Vascular Surgery. - : MOSBY-ELSEVIER. - 0741-5214 .- 1097-6809. ; 77:6, s. 1588-1597
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Tidskriftsartikel (refereegranskat)abstract
- Objective: The aim of this study was to compare outcomes of single or multistage approach during fenestrated-branched endovascular aortic repair (FB-EVAR) of extensive thoracoabdominal aortic aneurysms (TAAAs).Methods: We reviewed the clinical data of consecutive patients treated by FB-EVAR for extent I to III TAAAs in 24 centers (2006-2021). All patients received a single brand manufactured patient-specific or off-the-shelf fenestrated-branched stent grafts. Staging strategies included proximal thoracic aortic repair, minimally invasive segmental artery coil embolization, temporary aneurysm sac perfusion and combinations of these techniques. Endpoints were analyzed for elective repair in patients who had a single-or multistage approach before and after propensity score adjustment for baseline differences, including the composite 30-day/in-hospital mortality and/or permanent paraplegia, major adverse event, patient survival, and freedom from aortic-related mortality.Results: A total of 1947 patients (65% male; mean age, 71 +/- 8 years) underwent FB-EVAR of 155 extent I (10%), 729 extent II (46%), and 713 extent III TAAAs (44%). A single-stage approach was used in 939 patients (48%) and a multistage approach in 1008 patients (52%). A multistage approach was more frequently used in patients undergoing elective compared with non-elective repair (55% vs 35%; P < .001). Staging strategies were proximal thoracic aortic repair in 743 patients (74%), temporary aneurysm sac perfusion in 128 (13%), minimally invasive segmental artery coil embolization in 10 (1%), and combinations in 127 (12%). Among patients undergoing elective repair (n = 1597), the composite endpoint of 30-day/in-hospital mortality and/or permanent paraplegia rate occurred in 14% of single-stage and 6% of multistage approach patients (P < .001). After adjustment with a propensity score, multistage approach was associated with lower rates of 30-day/in-hospital mortality and/or permanent paraplegia (odds ratio, 0.466; 95% confidence interval, 0.271-0.801; P = .006) and higher patient survival at 1 year (86.9 +/- 1.3% vs 79.6 +/- 1.7%) and 3 years (72.7 +/- 2.1% vs 64.2 +/- 2.3%; adjusted hazard ratio, 0.714; 95% confidence interval, 0.528-0.966; P = .029), compared with a single stage approach.Conclusions: Staging elective FB-EVAR of extent I to III TAAAs was associated with decreased risk of mortality and/or permanent paraplegia at 30 days or within hospital stay, and with higher patient survival at 1 and 3 years.
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| 15. |
- Ferreira, Alexandra Gabriela, et al.
(författare)
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Restoring tumor immunogenicity with dendritic cell reprogramming
- 2022
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Ingår i: Cancer immunology research. - 2326-6074. ; 10:12 suppl
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Konferensbidrag (refereegranskat)abstract
- Immunotherapy is revolutionizing cancer treatment, but success is limited to a fraction of patients. Tumor immunosurveillance and immunotherapy relies on presentation of tumor-associated antigens by conventional dendritic cells type 1 (cDC1). However, tumors develop mechanisms to avoid immune recognition such as downregulation of antigen presentation and exclusion of cDC1. We have previously demonstrated that enforced expression of the transcription factors PU.1, IRF8 and BATF3 (PIB) imposes the lineage conversion of fibroblasts to cDC1 by direct cell reprogramming. Here, we hypothesize that PIB reprograms cancer cells directly into functional tumor-antigen presenting cells (tumor-APCs) with enhanced immunogenicity. First, we show that enforced expression of PIB in a wide range of murine and human cancer cells from different origins is sufficient to induce surface expression of hematopoietic and DC-lineage specific markers (CD45 and Clec9a). Moreover, reprogramming restored the expression of antigen presentation complexes (MHC-I and MHC-II) and activated the expression of the co-stimulatory molecules CD40, CD80 and CD86, required for productive T cell activation. Transcriptomic analysis using mRNA-sequencing showed that PIB imposes a global cDC1 gene signature and an antigen presentation program in tumor cells as early as day 3 of reprogramming, overriding the original cancer cell program. Furthermore, Assay for Transposase-Accessible Chromatin (ATAC) sequencing analysis revealed that PIB-mediated cDC1 reprogramming elicited rapid epigenetic remodeling followed by gradual rewiring of transcriptional program and stabilization of cDC1 identity. Functionally, tumor-APCs present endogenous antigens on MHC-I, prime naïve CD8+ T and become prone to CD8+ T cell mediated killing. Tumor-APCs secrete pro-inflammatory cytokines (IL-12) and chemoattractants (CXCL10), uptake and process exogenous antigens, phagocyte dead cells, and cross-present exogenous antigens to activate naïve T-cells. In addition, reprogrammed tumor cells harboring TP53, KRAS and PTEN mutations downregulated proliferation and showed impaired tumorigenicity in vitro and in vivo. Importantly, we show that intra-tumoral injection of reprogrammed tumor-APCs elicited tumour growth control in vivo alongside increasing infiltration of CD8+ T and NK cells in B16-OVA tumors. Finally, we showed that our approach can be employed to convert primary cancer cells derived from melanoma, lung, breast, pancreatic, urothelial, and head and neck carcinomas as well as cancer associated fibroblasts. In summary, we provide evidence for the direct reprogramming of tumor cells into immunogenic cDC1-like cells, with restored antigen presentation capacity and the ability to reinstate anti-tumor immunity. Our approach elicits the immune system against cancer and counteract major tumor evasion mechanisms including tumor heterogeneity and impaired antigen presentation, laying the foundation for developing immunotherapeutic strategies based on the cellular reprogramming of human cancer cells.
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| 16. |
- Ferreira, Catarina, et al.
(författare)
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Genetic variation in the conjugative plasmidome of a hospital effluent multidrug resistant Escherichia coli strain
- 2019
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Ingår i: Chemosphere. - : Elsevier BV. - 0045-6535 .- 1879-1298. ; 220, s. 748-759
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Tidskriftsartikel (refereegranskat)abstract
- Bacteria harboring conjugative plasmids have the potential for spreading antibiotic resistance through horizontal gene transfer. It is described that the selection and dissemination of antibiotic resistance is enhanced by stressors, like metals or antibiotics, which can occur as environmental contaminants. This study aimed at unveiling the composition of the conjugative plasmidome of a hospital effluent multidrug resistant Escherichia coli strain (H1FC54) under different mating conditions. To meet this objective, plasmid pulsed field gel electrophoresis, optical mapping analyses and DNA sequencing were used in combination with phenotype analysis. Strain H1FC54 was observed to harbor five plasmids, three of which were conjugative and two of these, pH1FC54_330 and pH1FC54_140, contained metal and antibiotic resistance genes. Transconjugants obtained in the absence or presence of tellurite (0.5 μM or 5 μM), arsenite (0.5 μM, 5 μM or 15 μM) or ceftazidime (10 mg/L) and selected in the presence of sodium azide (100 mg/L) and tetracycline (16 mg/L) presented distinct phenotypes, associated with the acquisition of different plasmid combinations, including two co-integrate plasmids, of 310 kbp and 517 kbp. The variable composition of the conjugative plasmidome, the formation of co-integrates during conjugation, as well as the transfer of non-transferable plasmids via co-integration, and the possible association between antibiotic, arsenite and tellurite tolerance was demonstrated. These evidences bring interesting insights into the comprehension of the molecular and physiological mechanisms that underlie antibiotic resistance propagation in the environment.
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| 17. |
- Hannan, Katherine M., et al.
(författare)
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Nuclear stabilization of p53 requires a functional nucleolar surveillance pathway
- 2022
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Ingår i: Cell Reports. - : Elsevier BV. - 2211-1247. ; 41:5
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Tidskriftsartikel (refereegranskat)abstract
- The nucleolar surveillance pathway monitors nucleolar integrity and responds to nucleolar stress by mediating binding of ribosomal proteins to MDM2, resulting in p53 accumulation. Inappropriate pathway activation is implicated in the pathogenesis of ribosomopathies, while drugs selectively activating the pathway are in trials for cancer. Despite this, the molecular mechanism(s) regulating this process are poorly understood. Using genome-wide loss-of-function screens, we demonstrate the ribosome biogenesis axis as the most potent class of genes whose disruption stabilizes p53. Mechanistically, we identify genes critical for regulation of this pathway, including HEATR3. By selectively disabling the nucleolar surveillance pathway, we demonstrate that it is essential for the ability of all nuclear-acting stresses, including DNA damage, to induce p53 accumulation. Our data support a paradigm whereby the nucleolar surveillance pathway is the central integrator of stresses that regulate nuclear p53 abundance, ensuring that ribosome biogenesis is hardwired to cellular proliferative capacity.
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| 18. |
- Harzing, Anne-Wil, et al.
(författare)
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Rating versus ranking : What is the best way to reduce response and language bias in cross-national research?
- 2009
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Ingår i: International Business Review. - : Elsevier BV. - 0969-5931 .- 1873-6149. ; 18:4, s. 417-432
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Tidskriftsartikel (refereegranskat)abstract
- We propose solutions to two recurring problems in cross-national research: response style differences and language bias. In order to do so, we conduct a methodological comparison of two different response formats-rating and ranking. For rating, we assess the effect of changing the commonly used 5-point Likert scales to 7-point Likert scales. For ranking, we evaluate the validity of presenting respondents with short scenarios for which they need to rank their top 3 solutions. Our results - based on two studies of 1965 undergraduate and 1714 MBA students in 16 different countries - confirm our hypotheses that both solutions reduce response and language bias, but show that ranking generally is a superior solution. These findings allow researchers to have greater confidence in the validity of cross-national differences if these response formats are used, instead of the more traditional 5-point Likert scales. In addition, our findings have several practical implications for multinational corporations, relating to issues such as selection interviews, performance appraisals, and cross-cultural training.
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| 19. |
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| 20. |
- McCarthy, Randy J., et al.
(författare)
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Registered Replication Report on Srull and Wyer (1979)
- 2018
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Ingår i: Advances in Methods and Practices in Psychological Science. - : SAGE Publications Inc. - 2515-2459 .- 2515-2467. ; 1:3, s. 321-336
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Tidskriftsartikel (refereegranskat)abstract
- Srull and Wyer (1979) demonstrated that exposing participants to more hostility-related stimuli caused them subsequently to interpret ambiguous behaviors as more hostile. In their Experiment 1, participants descrambled sets of words to form sentences. In one condition, 80% of the descrambled sentences described hostile behaviors, and in another condition, 20% described hostile behaviors. Following the descrambling task, all participants read a vignette about a man named Donald who behaved in an ambiguously hostile manner and then rated him on a set of personality traits. Next, participants rated the hostility of various ambiguously hostile behaviors (all ratings on scales from 0 to 10). Participants who descrambled mostly hostile sentences rated Donald and the ambiguous behaviors as approximately 3 scale points more hostile than did those who descrambled mostly neutral sentences. This Registered Replication Report describes the results of 26 independent replications (N = 7,373 in the total sample; k = 22 labs and N = 5,610 in the primary analyses) of Srull and Wyer?s Experiment 1, each of which followed a preregistered and vetted protocol. A random-effects meta-analysis showed that the protagonist was seen as 0.08 scale points more hostile when participants were primed with 80% hostile sentences than when they were primed with 20% hostile sentences (95% confidence interval, CI = [0.004, 0.16]). The ambiguously hostile behaviors were seen as 0.08 points less hostile when participants were primed with 80% hostile sentences than when they were primed with 20% hostile sentences (95% CI = [?0.18, 0.01]). Although the confidence interval for one outcome excluded zero and the observed effect was in the predicted direction, these results suggest that the currently used methods do not produce an assimilative priming effect that is practically and routinely detectable.
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| 21. |
- Rudke, Anderson Paulo, et al.
(författare)
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Land cover data of Upper Parana River Basin, South America, at high spatial resolution
- 2019
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Ingår i: International Journal of Applied Earth Observation and Geoinformation. - : Elsevier BV. - 1569-8432. ; 83
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Tidskriftsartikel (refereegranskat)abstract
- This study presents a new land cover map for the Upper Paraná River Basin (UPRB-2015), with high spatial resolution (30 m), and a high number of calibration and validation sites. To the new map, 50 Landsat-8 scenes were classified with the Support Vector Machine (SVM) algorithm and their level of agreement was assessed using overall accuracy and Kappa coefficient. The generated map was compared by area and by pixel with six global products (MODIS, GlobCover, Globeland30, FROM-GLC, CCI-LC and, GLCNMO). The results of the new classification showed an overall accuracy ranging from 67% to 100%, depending on the sub-basin (80.0% for the entire UPRB). Kappa coefficient was observed ranging from 0.50 to 1.00 (average of 0.73 in the whole basin). Anthropic areas cover more than 70% of the entire UPRB in the new product, with Croplands covering 46.0%. The new mapped areas of croplands are consistent with local socio-economic statistics but don't agree with global products, especially FROM-GLC (14,9%), MODIS (33.8%), GlobCover (71.2%), and CCI (67.8%). In addition, all global products show generalized spatial disagreement, with some sub-basins showing areas of cropland varying by an order of magnitude, compared to UPRB-2015. In the case of Grassland, covering 25.6% of the UPRB, it was observed a strong underestimation by all global products. Even for the Globeland30 and MODIS, which show some significant fraction of pasture areas, there is a high level of disagreement in the spatial distribution. In terms of general agreement, the seven compared mappings (including the new map) agree in only 6.6% of the study area, predominantly areas of forest and agriculture. Finally, the new classification proposed in this study provides better inputs for regional studies, especially for those involving hydrological modeling as well as offers a more refined LU/LC data set for atmospheric numerical models.
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| 22. |
- Silvério-Alves, Rita, et al.
(författare)
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GATA2 mitotic bookmarking is required for definitive haematopoiesis
- 2023
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Ingår i: Nature Communications. - 2041-1723. ; 14:1
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Tidskriftsartikel (refereegranskat)abstract
- In mitosis, most transcription factors detach from chromatin, but some are retained and bookmark genomic sites. Mitotic bookmarking has been implicated in lineage inheritance, pluripotency and reprogramming. However, the biological significance of this mechanism in vivo remains unclear. Here, we address mitotic retention of the hemogenic factors GATA2, GFI1B and FOS during haematopoietic specification. We show that GATA2 remains bound to chromatin throughout mitosis, in contrast to GFI1B and FOS, via C-terminal zinc finger-mediated DNA binding. GATA2 bookmarks a subset of its interphase targets that are co-enriched for RUNX1 and other regulators of definitive haematopoiesis. Remarkably, homozygous mice harbouring the cyclin B1 mitosis degradation domain upstream Gata2 partially phenocopy knockout mice. Degradation of GATA2 at mitotic exit abolishes definitive haematopoiesis at aorta-gonad-mesonephros, placenta and foetal liver, but does not impair yolk sac haematopoiesis. Our findings implicate GATA2-mediated mitotic bookmarking as critical for definitive haematopoiesis and highlight a dependency on bookmarkers for lineage commitment.
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| 23. |
- Tavares Ferreira, Joana, et al.
(författare)
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Choroidal thickness in diabetic patients without diabetic retinopathy
- 2018
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Ingår i: Retina. - 0275-004X .- 1539-2864. ; 38:4, s. 795-804
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Tidskriftsartikel (refereegranskat)abstract
- PURPOSE: To compare choroidal thickness (CT) between diabetic patients without diabetic retinopathy and a nondiabetic group. To explore how CT relates to disease duration, mean arterial pressure, glycemia, glycosylated hemoglobin, intraocular pressure, and ocular pulse amplitude.METHODS: Choroidal thickness was assessed using a spectral-domain optical coherence tomography and enhanced depth mode at 13 locations (subfoveal and 3 measurements 500 μm apart in 4 directions-nasal, temporal, superior, and inferior). Linear regression models were used.RESULTS: One hundred seventy-five patients were recruited (125 diabetic patients without diabetic retinopathy and 50 nondiabetic patients). In diabetic patients, although without statistical significance, CT showed a trend to be thicker in all locations (6.16-24.27 μm). Choroidal thickness was negatively associated with age (P < 0.001) in both groups, but only in the diabetic group, it was positively associated to ocular pulse amplitude (with a mean increase between 8.5 μm and 11.6 μm for each millimeter of mercury increase in ocular pulse amplitude). Diabetic patients' CT seems to stabilize after 150 months of diabetes, increase with higher glycemia levels (>160 mg/dL) while showing no fluctuation with glycosylated hemoglobin and mean arterial pressure.CONCLUSION: There seems to be a thickening of the choroid in diabetic patients without diabetic retinopathy. Moreover, this tissue may be functionally different in diabetes, as the pattern of associations seems to differ between groups.
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| 24. |
- Verschuere, Bruno, et al.
(författare)
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Registered Replication Report on Mazar, Amir, and Ariely (2008)
- 2018
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Ingår i: Advances in Methods and Practices in Psychological Science. - : SAGE Publications. - 2515-2459 .- 2515-2467. ; 1:3, s. 299-317
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Tidskriftsartikel (refereegranskat)abstract
- The self-concept maintenance theory holds that many people will cheat in order to maximize self-profit, but only to the extent that they can do so while maintaining a positive self-concept. Mazar, Amir, and Ariely (2008, Experiment 1) gave participants an opportunity and incentive to cheat on a problem-solving task. Prior to that task, participants either recalled the Ten Commandments (a moral reminder) or recalled 10 books they had read in high school (a neutral task). Results were consistent with the self-concept maintenance theory. When given the opportunity to cheat, participants given the moral-reminder priming task reported solving 1.45 fewer matrices than did those given a neutral prime (Cohen’s d = 0.48); moral reminders reduced cheating. Mazar et al.’s article is among the most cited in deception research, but their Experiment 1 has not been replicated directly. This Registered Replication Report describes the aggregated result of 25 direct replications (total N = 5,786), all of which followed the same preregistered protocol. In the primary meta-analysis (19 replications, total n = 4,674), participants who were given an opportunity to cheat reported solving 0.11 more matrices if they were given a moral reminder than if they were given a neutral reminder (95% confidence interval = [−0.09, 0.31]). This small effect was numerically in the opposite direction of the effect observed in the original study (Cohen’s d = −0.04).
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| 25. |
- Zander, Lena, et al.
(författare)
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Action Intent : Getting closer to leadership behaviour in 22 countries.
- 2020
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Ingår i: Research Handbook of Global Leadership. - Cheltenham : Edward Elgar Publishing. - 978 1 78254 534 7 - 978 1 78254 535 4 ; , s. 54-75
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Bokkapitel (övrigt vetenskapligt/konstnärligt)abstract
- The field of cross-cultural leadership has seen a boom in empirical research over the last few decades, yet there are still few large-scale studies that seek explanations for leadership behavior. Earlier research has provided knowledge and awareness about differences and similarities in leadership attitudes, ideals, perceptions and preferences across countries and cultures, but to predict leadership behavior remains difficult. In this chapter, leader’s ‘action intent’ is proposed as a ‘close-to-action’ concept in contrast to the more ‘far-from-action’ concepts used in earlier leadership research. Importantly, for ‘close-to-action’ concepts to be able to provide better predictions these need to provide contextual and situational cues. In our study, carried out in 22 countries, respondents have ranked their preferred action alternative for six specific leadership scenarios. We find inter-country and intra-country variation in action intent for each scenario and meaningful correlations with culturally endorsed leadership ideals. Drawing on our empirical illustration we provide implications from our findings for global leadership. And although there are no simple answers as to how to predict leadership behavior, we posit that using ‘action intent’ as a leadership measure will generate a better understanding and provide stronger predictions of leader behavior globally.
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| 26. |
- Zander, Lena, et al.
(författare)
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Standardization versus Contextualization : A study of language and leadership across 17 countries
- 2011
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Ingår i: Journal of world business (Print). - : Elsevier. - 1090-9516 .- 1878-5573. ; 46:3, s. 296-304
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Tidskriftsartikel (refereegranskat)abstract
- With multinational corporations increasingly adopting English as a corporate language, the issue of language management and the pros and cons of language standardization have been widely debated in the literature. Our 17-country study considers whether the use of English as a common corporate language causes difficulties. We empirically examine whether managerial reactions to specific leadership scenario-based situations change as a consequence of the language they use. Our results show that the choice of language (native or English) does not matter much for the studied leadership scenarios. Instead, leadership decisions and reactions depend more on cultural and situational context.
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| 27. |
- Zimmermannova, Olga, et al.
(författare)
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Restoring tumor immunogenicity with dendritic cell reprogramming
- 2023
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Ingår i: Science Immunology. - 2470-9468. ; 8:85
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Tidskriftsartikel (refereegranskat)abstract
- Decreased antigen presentation contributes to the ability of cancer cells to evade the immune system. We used the minimal gene regulatory network of type 1 conventional dendritic cells (cDC1) to reprogram cancer cells into professional antigen-presenting cells (tumor-APCs). Enforced expression of the transcription factors PU.1, IRF8, and BATF3 (PIB) was sufficient to induce the cDC1 phenotype in 36 cell lines derived from human and mouse hematological and solid tumors. Within 9 days of reprogramming, tumor-APCs acquired transcriptional and epigenetic programs associated with cDC1 cells. Reprogramming restored the expression of antigen presentation complexes and costimulatory molecules on the surfaces of tumor cells, allowing the presentation of endogenous tumor antigens on MHC-I and facilitating targeted killing by CD8 + T cells. Functionally, tumor-APCs engulfed and processed proteins and dead cells, secreted inflammatory cytokines, and cross-presented antigens to naïve CD8 + T cells. Human primary tumor cells could also be reprogrammed to increase their capability to present antigen and to activate patient-specific tumor-infiltrating lymphocytes. In addition to acquiring improved antigen presentation, tumor-APCs had impaired tumorigenicity in vitro and in vivo. Injection of in vitro generated melanoma-derived tumor-APCs into subcutaneous melanoma tumors delayed tumor growth and increased survival in mice. Antitumor immunity elicited by tumor-APCs was synergistic with immune checkpoint inhibitors. Our approach serves as a platform for the development of immunotherapies that endow cancer cells with the capability to process and present endogenous tumor antigens.
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