| 1. |
- Buch, S., et al.
(author)
-
Genetic variation in TERT modifies the risk of hepatocellular carcinoma in alcohol-related cirrhosis: results from a genome-wide case-control study
- 2023
-
In: Gut. - : BMJ. - 0017-5749 .- 1468-3288. ; 72:2, s. 381-391
-
Journal article (peer-reviewed)abstract
- Objective Hepatocellular carcinoma (HCC) often develops in patients with alcohol-related cirrhosis at an annual risk of up to 2.5%. Some host genetic risk factors have been identified but do not account for the majority of the variance in occurrence. This study aimed to identify novel susceptibility loci for the development of HCC in people with alcohol related cirrhosis. Design Patients with alcohol-related cirrhosis and HCC (cases: n=1214) and controls without HCC (n=1866), recruited from Germany, Austria, Switzerland, Italy and the UK, were included in a two-stage genome-wide association study using a case-control design. A validation cohort of 1520 people misusing alcohol but with no evidence of liver disease was included to control for possible association effects with alcohol misuse. Genotyping was performed using the InfiniumGlobal Screening Array (V.24v2, Illumina) and the OmniExpress Array (V.24v1-0a, Illumina). Results Associations with variants rs738409 in PNPLA3 and rs58542926 in TM6SF2 previously associated with an increased risk of HCC in patients with alcohol-related cirrhosis were confirmed at genome-wide significance. A novel locus rs2242652(A) in TERT (telomerase reverse transcriptase) was also associated with a decreased risk of HCC, in the combined meta-analysis, at genome-wide significance (p=6.41x10(-9), OR=0.61 (95% CI 0.52 to 0.70). This protective association remained significant after correction for sex, age, body mass index and type 2 diabetes (p=7.94x10(-5), OR=0.63 (95% CI 0.50 to 0.79). Carriage of rs2242652(A) in TERT was associated with an increased leucocyte telomere length (p=2.12x10(-44)). Conclusion This study identifies rs2242652 in TERT as a novel protective factor for HCC in patients with alcohol-related cirrhosis.
|
|
| 2. |
|
|
| 3. |
- Alisjahbana, A, et al.
(author)
-
CD5 Surface Expression Marks Intravascular Human Innate Lymphoid Cells That Have a Distinct Ontogeny and Migrate to the Lung
- 2021
-
In: Frontiers in immunology. - : Frontiers Media SA. - 1664-3224. ; 12, s. 752104-
-
Journal article (peer-reviewed)abstract
- Innate lymphoid cells (ILCs) contribute to immune defense, yet it is poorly understood how ILCs develop and are strategically positioned in the lung. This applies especially to human ILCs due to the difficulty of studying them in vivo. Here we investigated the ontogeny and migration of human ILCs in vivo with a humanized mouse model (“MISTRG”) expressing human cytokines. In addition to known tissue-resident ILC subsets, we discovered CD5-expressing ILCs that predominantly resided within the lung vasculature and in the circulation. CD5+ ILCs contained IFNγ-producing mature ILC1s as well as immature ILCs that produced ILC effector cytokines under polarizing conditions in vitro. CD5+ ILCs had a distinct ontogeny compared to conventional CD5- ILCs because they first appeared in the thymus, spleen and liver rather than in the bone marrow after transplantation of MISTRG mice with human CD34+ hematopoietic stem and progenitor cells. Due to their strategic location, human CD5+ ILCs could serve as blood-borne sentinels, ready to be recruited into the lung to respond to environmental challenges. This work emphasizes the uniqueness of human CD5+ ILCs in terms of their anatomical localization and developmental origin compared to well-studied CD5- ILCs.
|
|
| 4. |
|
|
| 5. |
- Evren, Elza, et al.
(author)
-
Distinct developmental pathways from blood monocytes generate human lung macrophage diversity
- 2021
-
In: Immunity. - : Elsevier. - 1074-7613 .- 1097-4180. ; 51, s. 35-35
-
Journal article (peer-reviewed)abstract
- The study of human macrophages and their ontogeny is an important unresolved issue. Here, we use a humanized mouse model expressing human cytokines to dissect the development of lung macrophages from human hematopoiesis in vivo. Human CD34+ hematopoietic stem and progenitor cells (HSPCs) generated three macrophage populations, occupying separate anatomical niches in the lung. Intravascular cell labeling, cell transplantation, and fate-mapping studies established that classical CD14+ blood monocytes derived from HSPCs migrated into lung tissue and gave rise to human interstitial and alveolar macrophages. In contrast, non-classical CD16+ blood monocytes preferentially generated macrophages resident in the lung vasculature (pulmonary intravascular macrophages). Finally, single-cell RNA sequencing defined intermediate differentiation stages in human lung macrophage development from blood monocytes. This study identifies distinct developmental pathways from circulating monocytes to lung macrophages and reveals how cellular origin contributes to human macrophage identity, diversity, and localization in vivo.
|
|
| 6. |
- Jonauskaite, Domicele, et al.
(author)
-
A comparative analysis of colour–emotion associations in 16–88-year-old adults from 31 countries
- 2024
-
In: British Journal of Psychology. - : John Wiley and Sons Ltd. - 0007-1269 .- 2044-8295. ; 115:2, s. 275-
-
Journal article (peer-reviewed)abstract
- As people age, they tend to spend more time indoors, and the colours in their surroundings may significantly impact their mood and overall well-being. However, there is a lack of empirical evidence to provide informed guidance on colour choices, irrespective of age group. To work towards informed choices, we investigated whether the associations between colours and emotions observed in younger individuals also apply to older adults. We recruited 7393 participants, aged between 16 and 88 years and coming from 31 countries. Each participant associated 12 colour terms with 20 emotion concepts and rated the intensity of each associated emotion. Different age groups exhibited highly similar patterns of colour–emotion associations (average similarity coefficient of.97), with subtle yet meaningful age-related differences. Adolescents associated the greatest number but the least positively biased emotions with colours. Older participants associated a smaller number but more intense and more positive emotions with all colour terms, displaying a positivity effect. Age also predicted arousal and power biases, varying by colour. Findings suggest parallels in colour–emotion associations between younger and older adults, with subtle but significant age-related variations. Future studies should next assess whether colour–emotion associations reflect what people actually feel when exposed to colour.
|
|
| 7. |
- Jonauskaite, D., et al.
(author)
-
Universal Patterns in Color-Emotion Associations Are Further Shaped by Linguistic and Geographic Proximity
- 2020
-
In: Psychological Science. - : SAGE Publications Inc.. - 0956-7976 .- 1467-9280. ; 31:10, s. 1245-1260
-
Journal article (peer-reviewed)abstract
- Many of us “see red,” “feel blue,” or “turn green with envy.” Are such color-emotion associations fundamental to our shared cognitive architecture, or are they cultural creations learned through our languages and traditions? To answer these questions, we tested emotional associations of colors in 4,598 participants from 30 nations speaking 22 native languages. Participants associated 20 emotion concepts with 12 color terms. Pattern-similarity analyses revealed universal color-emotion associations (average similarity coefficient r =.88). However, local differences were also apparent. A machine-learning algorithm revealed that nation predicted color-emotion associations above and beyond those observed universally. Similarity was greater when nations were linguistically or geographically close. This study highlights robust universal color-emotion associations, further modulated by linguistic and geographic factors. These results pose further theoretical and empirical questions about the affective properties of color and may inform practice in applied domains, such as well-being and design. © The Author(s) 2020.
|
|
| 8. |
|
|
| 9. |
- Rowe, AD, et al.
(author)
-
A Novel Approach to Improve Newborn Screening for Congenital Hypothyroidism by Integrating Covariate-Adjusted Results of Different Tests into CLIR Customized Interpretive Tools
- 2021
-
In: International journal of neonatal screening. - : MDPI AG. - 2409-515X. ; 7:2
-
Journal article (peer-reviewed)abstract
- Newborn screening for congenital hypothyroidism remains challenging decades after broad implementation worldwide. Testing protocols are not uniform in terms of targets (TSH and/or T4) and protocols (parallel vs. sequential testing; one or two specimen collection times), and specificity (with or without collection of a second specimen) is overall poor. The purpose of this retrospective study is to investigate the potential impact of multivariate pattern recognition software (CLIR) to improve the post-analytical interpretation of screening results. Seven programs contributed reference data (N = 1,970,536) and two sets of true (TP, N = 1369 combined) and false (FP, N = 15,201) positive cases for validation and verification purposes, respectively. Data were adjusted for age at collection, birth weight, and location using polynomial regression models of the fifth degree to create three-dimensional regression surfaces. Customized Single Condition Tools and Dual Scatter Plots were created using CLIR to optimize the differential diagnosis between TP and FP cases in the validation set. Verification testing correctly identified 446/454 (98%) of the TP cases, and could have prevented 1931/5447 (35%) of the FP cases, with variable impact among locations (range 4% to 50%). CLIR tools either as made here or preferably standardized to the recommended uniform screening panel could improve performance of newborn screening for congenital hypothyroidism.
|
|
