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1.
A dual biomarker TK1 protein and CA125 or HE4-based algorithm as a better diagnostic tool than ROMA Index in early detection of ovarian cancer
Diana Cviič, K. K. Jagarlamudi, Leon Meglič, Erik Škof, Andrej Zore, David Lukanović, Staffan Eriksson, Joško Osredkar, 2023, izvirni znanstveni članek

Povzetek: Background: The early detection of ovarian cancer is presently not effective, and it is crucial to establish biomarkers for the early diagnosis of ovarian cancer to improve the survival of patients. Materials and methods: The aim of this study was to investigate the role of thymidine kinase 1 (TK1) in combination with CA 125 or HE4 to serve as a potential diagnostic biomarkers for ovarian cancer. In this study, a set of 198 serum samples consisting of 134 ovarian tumor patients and 64 healthy age-matched controls were analyzed. The TK1 protein levels in serum samples were determined using the AroCell TK 210 ELISA. Results: A combination of TK1 protein with CA 125 or HE4 showed better performance than either of them alone in the differentiation of early stage ovarian cancer from the healthy control group, but also a significantly better performance than the ROMA index. However, this was not observed using a TK1 activity test in combination with the other markers. Furthermore, the combination of TK1 protein and CA 125 or HE4 could differentiate early stage disease (stage I, II) more efficiently from advanced-stage (stage III, IV) disease (p < 0.0001). Conclusions: The combination of TK1 protein with CA 125 or HE4 increased the potential of detecting ovarian cancer at early stages.
Ključne besede: thymidine kinase 1, TK 210 ELISA, TK-liaison, CA 125, HE4, ROMA index, ovarian cancer
Objavljeno v DiRROS: 06.08.2026; Ogledov: 55; Prenosov: 32
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2.
Altered stool cytokine profiles and pro-onflammatory/anti-inflammatory imbalance in children with autism spectrum disorder : a developmental analysis
Petra Finderle, Maja Jekovec-Vrhovšek, Uršula Prosenc Zmrzljak, Damjan Osredkar, Gorazd Avguštin, Joško Osredkar, 2026, izvirni znanstveni članek

Povzetek: Background: Immune dysregulation and gut dysbiosis are increasingly implicated in autism spectrum disorder (ASD), but compartment-specific intestinal cytokine profiles remain poorly defined. Aim: To characterize stool cytokine profiles and pro-/anti-inflammatory balance in children with ASD across development. Methods: We analyzed stool samples from 283 children (109 controls, 104 mild ASD, 70 severe ASD; age 0.9–21.5 years) recruited at a tertiary centre. Nine cytokines (IFN-γ, IL-1α, IL-1β, IL-4, IL-6, IL-8, IL-10, IL-17, TNF-α) were measured using a Luminex multi-plex assay; IL-15 was excluded due to >70% missing values. Group comparisons used Mann–Whitney U tests, with age stratification at the cohort median (≤9.5 vs. >9.5 years). A composite pro-/anti-inflammatory ratio (IL-1α + IL-1β + IL-6 + IL-8 + IL-17 + TNF-α + IFN-γ divided by IL-4 + IL-10) was calculated. Results: In the overall cohort, stool IL-8 and IL-4 were significantly decreased in ASD versus controls (IL-8: median 0.36 vs. 0.49 ng/L, p = 0.0041; IL-4: 0.28 vs. 0.30 ng/L, p = 0.0316), with a graded reduction from controls to mild and severe ASD. Age-stratified analysis revealed that IL-8 reduction was confined to younger children (≤9.5 years; p = 0.0025) and absent in older children, while IL-1β was significantly reduced in younger ASD children and tended to reverse in older ASD children. The pro-/anti-inflammatory ratio was markedly elevated in severe ASD (median 491 vs. 209 in controls; p = 0.059), particularly in older children. Stool IL-8 and IL-1β correlated inversely with CARS scores within the ASD group. Conclusions: Children with ASD show decreased stool IL-8 and IL-4 and a shift toward a pro-inflammatory cytokine balance, with the strongest alterations during early childhood. These findings are consistent with the hypothesis of a developmental window of intestinal immune dysregulation in ASD, with stool IL-8 as the primary FDR-corrected finding. The present cross-sectional data do not establish causality and independent replication is required before clinical conclusions are drawn.
Ključne besede: autism spectrum disorder, cytokines, stool biomarkers, IL-8, IL-4, interleukin, gut–immune axis, CARS, developmental immunology
Objavljeno v DiRROS: 06.08.2026; Ogledov: 45; Prenosov: 34
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3.
Disturbed antioxidant capacity in patients with systemic sclerosis associates with lung and gastrointestinal symptoms
Neža Brezovec, Katja Perdan-Pirkmajer, Blaž Burja, Žiga Rotar, Joško Osredkar, Snežna Sodin-Šemrl, Katja Lakota, Saša Čučnik, 2023, izvirni znanstveni članek

Povzetek: The correct balance between reactive oxygen species and antioxidant defense in an organism is disturbed in oxidative stress. To assess oxidative balance in 36 SSc patients and 26 healthy controls (HCs), we measured reactive oxidative metabolites (ROMs), total antioxidant capacity (TAC), lipid peroxidation (measuring 4-HNE), and DNA oxidative damage (measuring 8-OHdG) in serum. Furthermore, DNA breaks in leukocytes of 35 SSc patients and 32 HCs were evaluated using COMET. While we report high ROMs for both SSc patients and age/sex matched HC samples, there was a significant increase in TAC in SSc patients as compared to HCs, and thus also a significantly higher oxidative stress index in SSc patients. TAC was significantly higher in SSc patients with ILD and gastrointestinal involvement, as well as in patients with anti-topoisomerase antibodies. We observe no difference in serum lipid peroxidation status or oxidative DNA damage. However, SSc patients had significantly more leukocyte DNA breaks than HCs; the most damage was observed in patients treated with immunosuppressives. Thus, our study confirms presence of oxidative stress and increased DNA damage in leukocytes of SSc patients; however, it points toward increased antioxidant capacity, which needs to be further studied.
Ključne besede: systemic sclerosis, oxidative stress, reactive oxidative metabolites, antioxidants, lipid peroxidation, DNA damage, DNA breaks
Objavljeno v DiRROS: 05.08.2026; Ogledov: 64; Prenosov: 49
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Idarubicin-loaded drug-eluting microspheres transarterial chemoembolization for intermediate stage hepatocellular carcinoma : safety, efficacy, and pharmacokinetics
Špela Koršič, Joško Osredkar, Lojze Šmid, Klemen Steblovnik, Mark Popović, Igor Locatelli, Jurij Trontelj, Peter Popović, 2024, izvirni znanstveni članek

Povzetek: Background: Transarterial chemoembolization (TACE) is the treatment of choice for the intermediate stage hepatocellular carcinoma (HCC). Doxorubicin remains the most used chemotherapeutic agent in TACE, although in vitro screening has demonstrated that idarubicin exhibits greater cytotoxicity against HCC. This study aimed to evaluate safety, efficacy, and pharmacokinetics of idarubicin-loaded drug-eluting microspheres TACE (DEMIDA-TACE) in intermediate stage HCC patients. Patients and methods: Between September 2019 and December 2021, 31 consecutive intermediate stage HCC patients (96.8% cirrhotic) were included to this study. 2 mL of LifePearl™ microspheres (100 μm) loaded with 10 mg of 1 mg/mL idarubicin were used for treatment. The adverse events, objective response rate (ORR), progression free survival (PFS), time to TACE untreatable progression (TTUP), median overall survival (mOS), and pharmacokinetics were evaluated. Results: There were 68 TACE procedures performed. Adverse events grade ≥ 3 were noted after 29.4% procedures. The ORR was 83.9%, median PFS and TTUP were 10.5 months (95% CI: 6.8-14.3 months) and 24.6 months (95% CI: 11.6-37.6 months), respectively. Median OS was 36.0 months (95% CI: 21.1-50.9 months). Significant differences between patients achieving objective response (OR) and those with progressive disease were observed regarding idarubicinol and combined idarubicin-idarubicinol plasma concentrations at 72 hours post-procedure, higher plasma concentrations were observed in patients achieving OR (p = 0.014 and 0.014; cut-off values 1.2 and 1.29 ng/mL, respectively). Conclusions: DEMIDA-TACE emerges as a safe and effective method of treatment for the intermediate stage HCC with low rates of adverse events alongside high tumor response, favourable disease control and overall survival. Idarubicinol and combined idarubicin-idarubicinol plasma concentrations at 72 hours post-procedure may serve as prognostic factors for achieving OR.
Ključne besede: drug-eluting microspheres transarterial chemoembolization, efficacy, hepatocellular carcinoma, idarubicin, pharmacokinetics, safety
Objavljeno v DiRROS: 26.06.2026; Ogledov: 187; Prenosov: 132
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6.
Association between autism spectrum disorder, trace elements, and intracranial fluid spaces
Matej Mlinarič, Maja Jekovec-Vrhovšek, David Neubauer, Alenka France Štiglic, Joško Osredkar, 2024, izvirni znanstveni članek

Povzetek: Autism spectrum disorder (ASD) belongs to the group of complex developmental disorders. Novel studies have suggested that genetic and environmental factors equally affect the risk of ASD. Identification of environmental factors involved in the development of ASD is therefore crucial for a better understanding of its etiology. Whether there is a causal link between trace elements, brain magnetic resonance imaging (MRI), and ASD remains a matter of debate and requires further studies. (2) In the prospective part of the study, we included 194 children, including an age-matched control group; in the retrospective study, 28 children with available MRI imaging were included. All children had urine analysis of trace elements performed. In those with available brain MRI, linear indexes for the ventricular volumes were measured and calculated. (3) We found the highest vanadium, rubidium, thallium, and silver levels in children with ASD. These elements also correlated with the estimated ventricular volume based on MRI indexes in children with ASD in the subanalysis. However, the severity of the deficits did not correlate with brain MRI indexes of our elements, except negatively with magnesium. (4) Trace elements have an impact on children with ASD, but further multi-centric studies are needed to explain the pathophysiological mechanisms.
Ključne besede: autism spectrum disorders, trace elements, ventricular indexes
Objavljeno v DiRROS: 11.06.2026; Ogledov: 170; Prenosov: 142
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7.
Cardiac troponins I and T as biomarkers of cardiomyocyte injury - advantages and disadvantages of each
Joško Osredkar, Amila Bajrić, Hugon Možina, Luka Lipar, Aleš Jerin, 2024, izvirni znanstveni članek

Povzetek: Measurement of cardiac troponin in serum is an essential part of diagnosing myocardial infarction in the emergency department. The guidelines suggest that high-sensitivity techniques should be used for measuring cardiac troponin I (cTnI) or cardiac troponin T (cTnT). The aim of our study was to correlate the values of both troponins, and to ascertain which type of troponin is more in agreement with the diagnosis. The patients were classified into four groups: 43 patients in non-ST-elevation myocardial infarction (NSTEMI), 7 in ST-elevation myocardial infarction (STEMI), 48 in Type 2 myocardial infarction, and 21 in the control group. A significant correlation between cTnI and cTnT was found in the NSTEMI (r = 0.70) and Type 2 (r = 0.75) groups while in the control group there was no association (r = −0.06). The ratios of cTnI and cTnT relative to their cut-off values were lower in Type 2 myocardial infarction compared to NSTEMI. This difference can be attributed to the pathophysiology of these two types of heart conditions. The ratio in the NSTEMI group was higher in female than in male patients (53.3 vs. 24.6 ng/L); the same difference was found for the ratio of cTnT (20.8 vs. 13.1 ng/L). In the same manner, the ratios in the Type 2 group were higher in female than in male patients for cTnI (25.6 vs. 12.7 ng/L) as well as for cTnT (19.0 vs. 6.73 ng/L). These differences could be due to biological differences, but they could also be influenced by other factors contributing to different damage responses.
Ključne besede: cardiac troponin I, cardiac troponin T, myocardial infarction
Objavljeno v DiRROS: 03.06.2026; Ogledov: 262; Prenosov: 211
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8.
Trace element dysregulation and detoxification dysfunction in autism spectrum disorder : a urinary biomarker study with element ratio analysis
Joško Osredkar, Uroš Godnov, Maja Jekovec-Vrhovšek, Damjan Osredkar, Gorazd Avguštin, Alenka France Štiglic, Teja Fabjan, Kristina Kumer, 2026, izvirni znanstveni članek

Povzetek: Background: Autism spectrum disorder (ASD) arises from complex gene–environment interactions. While trace element abnormalities have been studied, associations with autism severity remain inconsistent. Ratios indicating detoxification balance, rather than single toxic elements, may better reflect severity. Objective: To examine the relationships between urinary trace element levels, detoxification-related element ratios, and autism severity measured by the Childhood Autism Rating Scale (CARS). Methods: In a crosssectional study of 168 participants (103 ASD, 65 controls), thirty urinary trace elements were quantified by ICP-MS. ASD patients were stratified by CARS into subthreshold ASD (n = 29), mild–moderate ASD (n = 36), and severe ASD (n = 38). Analyses included Mann–Whitney U, Kruskal–Wallis, and Spearman correlation tests, focusing on Li/Pb, Cu/Pb, and Cr/Pb ratios. Results: Individual elements showed weak associations with CARS; lead correlated positively (ρ = 0.209, p = 0.035) and lithium inversely (ρ = −0.194, p = 0.051). In contrast, element ratios showed stronger links: Li/Pb (ρ = −0.349, p = 0.0003), Cu/Pb (ρ = −0.320, p = 0.0011), and Cr/Pb (ρ = −0.209, p = 0.035). Severe ASD exhibited modest 90th-percentile elevations for toxic elements but high heterogeneity. Conclusions: Single-element levels showed limited associations with ASD severity. Element ratios, particularly Li/Pb, showed stronger statistical associations than individual elements in this cross-sectional dataset; however, these findings should be interpreted as candidate correlates rather than causal or clinically validated biomarkers.
Ključne besede: autism spectrum disorder, trace elements, lead, llithium, detoxification, biomarkers, CARS, element ratios, environmental toxins, metallothionein
Objavljeno v DiRROS: 01.06.2026; Ogledov: 225; Prenosov: 165
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9.
Predicting early preterm delivery and late fetal growth restriction by TNFα : Elektronski vir
Adi Sharabi-Nov, Vesna Fabjan-Vodušek, Tanja Premru-Sršen, Kristina Kumer, Teja Fabjan, Nataša Tul, Joško Osredkar, Kypros H. Nicolaides, Berthold Huppertz, Hamutal Meiri, 2025, pregledni znanstveni članek

Povzetek: We evaluated tumor necrosis factor alpha (TNFα) and uterine artery pulsatility index (UtA-PI) in the triage of patients with suspected preterm delivery (PTD), preeclampsia (PE), fetal growth restriction (FGR), and PE+FGR. The study included 125 pregnant women attending high-risk pregnancy clinics for triage of pregnancy complications. There were 31 pure PE cases, 42 cases of PE combined with FGR, 16 pure FGR cases, 15 PTD cases, and 21 term normal delivery controls. Maternal serum TNFα was determined by immune-diagnostic testing. UtA-PI was measured by Doppler sonography. Demographic, medical and pregnancy history, and mean arterial blood pressure (MAP) were extracted from the hospital medical records. Linear regression coefficients, and Box and Whisker plots were calculated and depicted using non-parametric statistics (Kruskal Wallis and Mann–Whitney). Spearman’s regression coefficient assessed marker accuracy; p<0.05 was considered significant. It was found that high TNFα in cases <34 weeks gestation, when coupled to low UtA-PI and normal blood pressure are found in early PTD most likely linked to maternal inflammation. At term, high TNFα combined with high UtA-PI is associated with any FGR (with/without PE), possibly reflecting inflammation and maternal and fetal hypoxia due to the very long period of altered placental perfusion. Accordingly, TNFα, and Doppler UtA-PI could be used for the differential diagnosis of early PTD, and FGR (with/without PE) near delivery.
Ključne besede: fetal growth restriction, gestational week, inflammation, mean arterial blood pressure, placental hypoxia, placental perfusion, preeclampsia, pregnancy
Objavljeno v DiRROS: 18.05.2026; Ogledov: 241; Prenosov: 175
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10.
Thymidine kinase as a biomarker of chemoresistance in epithelial ovarian cancer using the KELIM model
David Lukanović, Joško Osredkar, Erik Škof, Diana Cviič, Aleš Jerin, Kaja Lešnik, Miha Matjašič, Leon Meglič, 2026, izvirni znanstveni članek

Povzetek: Background: Ovarian cancer (OC) remains the most lethal gynecological malignancy, with platinum sensitivity being a key determinant of treatment outcomes. The KELIM model, derived from CA-125 kinetics, is a promising biomarker for predicting chemosensitivity. Thymidine kinase 1 (TK1), a proliferation marker, has shown relevance in various cancers but its role in chemotherapy response for OC is unclear.Methods: In this retrospective study, we assessed the association between TK1 protein (TK1p) and enzymatic activity (TK1a) and chemosensitivity (KELIM), platinum-free interval (PFI), and chemotherapy response score (CRS) in 28 patients with epithelial OC treated with platinum-based chemotherapy. Biomarker dynamics were measured at multiple timepoints. KELIM was calculated using CA-125 kinetics; relationships with CRS and PFI were evaluated.Results: KELIM demonstrated robust predictive performance (correlating with favorable CRS [rho = 0.731, p = 0.011] and longer PFI [rho = 0.437, p = 0.007]). TK1p and TK1a showed no significant correlations with KELIM, PFI, or CRS. ROC analysis for preoperative TK1p yielded an AUC of 0.6941, indicating moderate discriminative potential. TK1a increased postoperatively but lacked predictive value for chemoresistance.Conclusion: Our findings reinforce the value of KELIM as a reliable predictor of platinum sensitivity in OC. TK1 dynamics reflect tumor proliferation but did not significantly predict chemotherapy response. Larger cohorts and further research are required to explore whether TK1 can complement established biomarkers.
Ključne besede: biomarker, CA-125, chemoresistance, epithelial ovarian cancer, KELIM, ovarian cancer, thymidine kinase
Objavljeno v DiRROS: 05.05.2026; Ogledov: 244; Prenosov: 215
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