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- Bauer, S, et al.
(författare)
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Identification of the Transcription Factor ATF3 as a Direct and Indirect Regulator of the LDLR
- 2022
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Ingår i: Metabolites. - : MDPI AG. - 2218-1989. ; 12:9
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Tidskriftsartikel (refereegranskat)abstract
- Coronary artery disease (CAD) is a complex, multifactorial disease caused, in particular, by inflammation and cholesterol metabolism. At the molecular level, the role of tissue-specific signaling pathways leading to CAD is still largely unexplored. This study relied on two main resources: (1) genes with impact on atherosclerosis/CAD, and (2) liver-specific transcriptome analyses from human and mouse studies. The transcription factor activating transcription factor 3 (ATF3) was identified as a key regulator of a liver network relevant to atherosclerosis and linked to inflammation and cholesterol metabolism. ATF3 was predicted to be a direct and indirect (via MAF BZIP Transcription Factor F (MAFF)) regulator of low-density lipoprotein receptor (LDLR). Chromatin immunoprecipitation DNA sequencing (ChIP-seq) data from human liver cells revealed an ATF3 binding motif in the promoter regions of MAFF and LDLR. siRNA knockdown of ATF3 in human Hep3B liver cells significantly upregulated LDLR expression (p < 0.01). Inflammation induced by lipopolysaccharide (LPS) stimulation resulted in significant upregulation of ATF3 (p < 0.01) and subsequent downregulation of LDLR (p < 0.001). Liver-specific expression data from human CAD patients undergoing coronary artery bypass grafting (CABG) surgery (STARNET) and mouse models (HMDP) confirmed the regulatory role of ATF3 in the homeostasis of cholesterol metabolism. This study suggests that ATF3 might be a promising treatment candidate for lowering LDL cholesterol and reducing cardiovascular risk.
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- Bizzarri, C, et al.
(författare)
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Residual β-cell mass influences growth of prepubertal children with type 1 diabetes
- 2013
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Ingår i: Hormone research in paediatrics. - : S. Karger AG. - 1663-2826 .- 1663-2818. ; 80:4, s. 287-292
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Tidskriftsartikel (refereegranskat)abstract
- <b><i>Background:</i></b> The growth deceleration observed in children with type 1 diabetes (T1D) has been related to poor glycemic control. It is unclear whether growth impairment persists despite the optimization of therapy. We analyzed the effects of intensive insulin treatment on prepubertal growth. <b><i>Methods:</i></b> One hundred and four T1D children were evaluated from T1D diagnosis up to puberty onset. Height, weight, insulin requirement and glycated hemoglobin (HbA1c) were recorded at 3- to 6-month intervals. Residual β-cell mass was estimated by fasting C-peptide at T1D onset. <b><i>Results:</i></b> Age at T1D onset was 5.91 ± 1.9 years. Follow-up duration was 4.84 ± 1.58 years. Height velocity standard deviation score (SDS) was -0.14 ± 1.84. Height SDS changed from 0.52 ± 1.04 at T1D onset, to 0.36 ± 1.10 at the end of follow-up (p = 0.04). BMI SDS increased from -0.04 ± 1.48 to 0.32 ± 1.03 (p = 0.01). Multivariate analysis showed that height velocity was directly affected by C-peptide (p = 0.03) and insulin requirement (p = 0.004) and inversely related to HbA1c (p = 0.006). BMI gain was negatively influenced by HbA1c (p = 0.01) and positively related to T1D duration (p = 0.01). <b><i>Conclusion:</i></b> Despite insulin intensive therapy, T1D still negatively affects growth. Residual β-cell mass has a direct positive impact on growth, independently from the quality of glycemic control.
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- Kholova, Ivana, et al.
(författare)
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Inter- and intraobserver agreement in whole-slide digital ThinPrep samples of low-grade squamous lesions of the cervix uteri with known high-risk HPV status : A multicentric international study
- 2022
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Ingår i: Cancer Cytopathology. - : Wiley. - 1934-662X .- 1934-6638. ; 130:12, s. 939-948
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Tidskriftsartikel (refereegranskat)abstract
- Background High-risk human papilloma virus (HR HPV) testing and liquid-based cytology are used for primary cervical screening. Digital cytology, based on whole-slide scanned samples, is a promising technique for teaching and diagnostic purposes. The aim of our study was to evaluate the interobserver and intraobserver variation in low-grade squamous lesions, HR HPV status bias, and the use of whole-slide scanned digital cervical cytology slides. Methods Fifteen expert cytopathologists evaluated 71 digitalized ThinPrep slides (31 atypical squamous cells of undetermined significance [ASC-US], 21 negative for intraepithelial lesion or malignancy, and 19 low-grade squamous intraepithelial lesion cases). HR HPV data were accessible only in the second round. Results In interobserver analysis, Kendalls coefficient of concordance was 0.52 in the first round and 0.58 in the second round. Fleiss kappa values were 0.29 in the first round and 0.31 in the second round. In the ASC-US category, Fleiss kappa increased from 0.19 to 0.22 in the second round and the increase was even higher expressed by Kendalls coefficient: from 0.42 to 0.52. In intraobserver analysis, personal scores were higher in the second round. Conclusions The interobserver and intraobserver variability in low-grade squamous lesions was within fair agreement values in the present study, in line with previous works. The comparison of two rounds showed that expert cytopathologists are generally unbiased by the knowledge of HR HPV data, but that being informed of the HR HPV status leads to a better agreement. Stain quality and back discomfort were highlighted as factors affecting digital cytopathology use.
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- Paolini, Lucia, et al.
(författare)
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Large-scale production of extracellular vesicles: Report on the “massivEVs” ISEV workshop
- 2022
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Ingår i: Journal of Extracellular Biology. - : Wiley. - 2768-2811. ; 1:10
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Tidskriftsartikel (refereegranskat)abstract
- Extracellular vesicles (EVs) large-scale production is a crucial point for the translation of EVs from discovery to application of EV-based products. In October 2021, the International Society for Extracellular Vesicles (ISEV), along with support by the FET-OPEN projects, “The Extracellular Vesicle Foundry” (evFOUNDRY) and “Extracellular vesicles from a natural source for tailor-made nanomaterials” (VES4US), organized a workshop entitled “massivEVs” to discuss the potential challenges for translation of EV-based products. This report gives an overview of the topics discussed during “massivEVs”, the most important points raised, and the points of consensus reached after discussion among academia and industry representatives. Overall, the review of the existing EV manufacturing, upscaling challenges and directions for their resolution highlighted in the workshop painted an optimistic future for the expanding EV field.
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- Vigliar, Elena, et al.
(författare)
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COVID-19 pandemic impact on cytopathology practice in the post-lockdown period: An international, multicenter study
- 2022
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Ingår i: Cancer Cytopathology. - : WILEY. - 1934-662X .- 1934-6638. ; 130:5, s. 344-351
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Tidskriftsartikel (refereegranskat)abstract
- Background In a previous worldwide survey, the authors showed a drastic reduction in the number of cytological specimens processed during the coronavirus disease 2019 "lockdown" period along with an increase in malignancy rates. To assess the continued impact of the pandemic on cytological practices around the world, they undertook a second follow-up worldwide survey collecting data from the post-lockdown period (2020). Methods Participants were asked to provide data regarding their cytopathology activity during the first 12 weeks of their respective national post-lockdown period (2020), which ranged from April 4 to October 31. Differences between the post-lockdown period and the corresponding 2019 period were evaluated, and the authors specifically focused on rates of malignant diagnoses. Results A total of 29 respondents from 17 countries worldwide joined the survey. Overall, a lower number of cytological specimens (n = 236,352) were processed in comparison with the same period in 2019 (n = 321,466) for a relative reduction of 26.5%. The overall malignancy rate showed a statistically significant increase (12,442 [5.26%] vs 12,882 [4.01%]; P < .001) during the same time period. Similar results were obtained if both malignancy and suspicious for malignancy rates were considered together (15,759 [6.58%] vs 16,011 [4.98%]; P < .001). Conclusions The data showed a persistent reduction in the cytological specimen volume during the post-lockdown period (2020). However, the relative increase in the cytological workload in the late part of the post-lockdown is a promising finding of a slow return to normality.
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- Vigliar, Elena, et al.
(författare)
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Global impact of the COVID-19 pandemic on cytopathology practice: Results from an international survey of laboratories in 23 countries
- 2020
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Ingår i: Cancer Cytopathology. - : WILEY. - 1934-662X .- 1934-6638. ; 128:12, s. 885-894
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Tidskriftsartikel (refereegranskat)abstract
- Background To the authors knowledge, the impact of the coronavirus disease 2019 (COVID-19) pandemic on cytopathology practices worldwide has not been investigated formally. In the current study, data from 41 respondents from 23 countries were reported. Methods Data regarding the activity of each cytopathology laboratory during 4 weeks of COVID-19 lockdown were collected and compared with those obtained during the corresponding period in 2019. The overall number and percentage of exfoliative and fine-needle aspiration cytology samples from each anatomic site were recorded. Differences in the malignancy and suspicious rates between the 2 periods were analyzed using a meta-analytical approach. Results Overall, the sample volume was lower compared with 2019 (104,319 samples vs 190,225 samples), with an average volume reduction of 45.3% (range, 0.1%-98.0%). The percentage of samples from the cervicovaginal tract, thyroid, and anorectal region was significantly reduced (P < .05). Conversely, the percentage of samples from the urinary tract, serous cavities, breast, lymph nodes, respiratory tract, salivary glands, central nervous system, gastrointestinal tract, pancreas, liver, and biliary tract increased (P < .05). An overall increase of 5.56% (95% CI, 3.77%-7.35%) in the malignancy rate in nongynecological samples during the COVID-19 pandemic was observed. When the suspicious category was included, the overall increase was 6.95% (95% CI, 4.63%-9.27%). Conclusions The COVID-19 pandemic resulted in a drastic reduction in the total number of cytology specimens regardless of anatomic site or specimen type. The rate of malignancy increased, reflecting the prioritization of patients with cancer who were considered to be at high risk. Prospective monitoring of the effect of delays in access to health services during the lockdown period is warranted.
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