Abstract Transarterial chemoembolization (TACE) represent the standard of therapy for non-operative hepatocellular carcinoma (HCC), while prediction of long term treatment outcomes is a complex and ...multifactorial task. In this study, we present a novel machine learning approach utilizing radiomics features from multiple organ volumes of interest (VOIs) to predict TACE outcomes for 252 HCC patients. Unlike conventional radiomics models requiring laborious manual segmentation limited to tumoral regions, our approach captures information comprehensively across various VOIs using a fully automated, pretrained deep learning model applied to pre-TACE CT images. Evaluation of radiomics random survival forest models against clinical ones using Cox proportional hazard demonstrated comparable performance in predicting overall survival. However, radiomics outperformed clinical models in predicting progression-free survival. Explainable analysis highlighted the significance of non-tumoral VOI features, with their cumulative importance superior to features from the largest liver tumor. The proposed approach overcomes the limitations of manual VOI segmentation, requires no radiologist input and highlight the clinical relevance of features beyond tumor regions. Our findings suggest the potential of this radiomics models in predicting TACE outcomes, with possible implications for other clinical scenarios.
A series of thiosemicarbazone derivatives was prepared and their anti-tumor activity in vitro was tested. The X-ray investigation performed for compounds T2, T3 and T5 confirmed the synthesis pathway ...and assumed molecular structures of analyzed thiosemicarbazones. The conformational preferences of the thiosemicarbazone system were characterized using theoretical calculations by AM1 method. Selected compounds were converted into complexes of Cu (II) ions. The effect of complexing on anti-tumor activity has been investigated. The copper(II) complexes, with Schiff bases T1, T10, T12, T13, and T16 have been synthesized and characterized by chemical and elemental analysis, FTIR spectroscopy and TGA method. Thermal properties of coordination compounds were studied using TG-DTG techniques under dry air atmosphere. G361, A375, and SK-MEL-28 human melanoma cells and BJ human normal fibroblast cells were treated with tested compounds and their cytotoxicity was evaluated with MTT test. The compounds with the most promising anti-tumour activity were then selected and their cytotoxicity was verified with cell cycle analysis and apoptosis/necrosis detection. Additionally, DNA damages in the form of a basic sites presence and the expression of oxidative stress and DNA damage response genes were evaluated. The obtained results indicate that complexation of thiosemicarbazone derivatives with Cu (II) ions improves their antitumor activity against melanoma cells. The observed cytotoxic effect is associated with DNA damage and G2/M phase of cell cycle arrest as well as disorders of the antioxidant enzymes expression.
During firing from a mortar, an important issue is the parameters of compressibility of the ground on which the mortar is placed. This affects the operation of the mortar (including safety). During ...the qualification tests of the mortar, the influence of different types of terrains on its strength and work during shooting should be examined. Until now, in the Polish standardization documents there was no clear description of the ground parameters used for these kinds of tests. Analysis of the literature also did not allow to determine the dependence of the mortars displacement in the function of the type of ground and its geotechnical parameters. In view of the above, it has become important to draw up a research problem in the form of determining the types of soil with parameters, enabling the mortar tests to be carried out in conditions as close as possible to combat conditions. Therefore, the authors carried out the theoretical calculations and field tests with the use of geotechnical methods such as static and dynamic load tests to determine the parameters of the ground for mortar testing. Preliminary tests were conducted using the prescribed measurement methods and a comparative mortar firing test. Subsequently, an analysis of the results was carried out and the possibilities of using the tested methods of measuring the parameters of soil compressibility were determined.
Leber’s hereditary optic neuropathy (LHON) is one of the most common mitochondrial diseases caused by point mutations in mitochondrial DNA (mtDNA). The majority of diagnosed LHON cases are caused by ...a point mutation at position 11,778 in the mitochondrial genome. LHON mainly affects young men in their 20s and 30s with usually poor visual prognosis. It remains unexplained why men are more likely to develop the disease and why only retinal ganglion cells are affected. In this study, a cell model was used for the first time to investigate the influence of testosterone on the cell death mechanism apoptosis and on an autophagy/mitophagy. Cells with m.11778G > A were found to be significantly more susceptible to nucleosome formation and effector caspase activation that serve as hallmarks of apoptotic cell death. Cells having this mutation expressed higher levels of mitophagic receptors BNIP3 and BNIP3L/Nix in a medium with testosterone. Moreover, cells having the mutation exhibited greater mitochondrial mass, which suggests these cells have a decreased cell survival. The observed decrease in cell survival was supported by the observed increase in apoptotic cell death. Autophagy was analyzed after inhibition with Bafilomycin A1 (Baf A1). The results indicate impairment in autophagy in LHON cells due to lower autophagic flux supported by observed lower levels of autophagosome marker LC3-II. The observed impaired lower autophagic flux in mutant cells correlated with increased levels of BNIP3 and BNIP3L/Nix in mutant cells.
Objective. Decreased synthesis of sex hormone-binding globulin (SHBG) related to hyperinsulinemia is one of the disturbances characteristic of polycystic ovary syndrome (PCOS). Hyperinsulinemia is a ...compensatory mechanism for liver insulin resistance (IR); thus, SHBG may be considered as a surrogate marker of liver IR. Therefore, this study aimed to assess the prediction of IR and impaired fasting glucose (IFG) based on SHBG levels in women with PCOS. Methods. This analysis included data retrieved from medical records of 854 patients with PCOS hospitalized in the Gynecological Endocrinology Clinic from 2012 to 2019. Data including anthropometric parameters, fasting plasma glucose, insulin, and SHBG levels were analyzed. BMI and HOMA-IR were calculated with standard formulas. Results. IFG and IR assessed based on HOMA-IR values > 2.0 were found in 19.5% and 47.8% of the study group, respectively. Empirical optimal cutoff values for SHBG levels were ≤41.5 nmol/L typical for IR (AUC 0.711, sensitivity 61.1%, specificity 71.6%, positive predictive value (PPV) 70.7%, and negative predictive value (NPV) 62.1%). The probability of insulin resistance occurrence for SHBG concentration 26.1 nmol/L (the lower normal range) was 61.6% (95% CI: 57.4%–65.8%). The SHBG concentration of 36.4 nmol/L and 8.1 nmol/L was related to a 10% and 20% probability of IFG, respectively. Conclusion. In conclusion, this is the first study estimating the probability of liver IR and IFG occurrence based on SHBG levels in women with PCOS. Despite the low sensitivity, SHBG level below 42 nmol/L should cause closer monitoring for the fatty liver and prediabetes.
Leber hereditary optic neuropathy (LHON) is a mitochondrial disorder with symptoms limited to a single tissue, optic nerve, resulting in vision loss. In the majority of cases it is caused by one of ...three point mutations in mitochondrial DNA (mtDNA) but their presence is not sufficient for disease development, since ~50% of men and ~10% women who carry them are affected. Thus additional modifying factors must exist. In this study, we use next generation sequencing to investigate the role of whole mtDNA variation in male Polish patients with LHON and m.11778G > A, the most frequent LHON mutation. We present a possible association between mtDNA haplogroup K and variants in its background, a combination of m.3480A > G, m.9055G > A, m.11299 T > C and m.14167C > T, and LHON mutation. These variants may have a negative effect on m.11778G > A increasing its penetrance and the risk of LHON in the Polish population. Surprisingly, we did not observe associations previously reported for m.11778G > A and LHON in European populations, particularly for haplogroup J as a risk factor, implying that mtDNA variation is much more complex. Our results indicate possible contribution of novel combination of mtDNA genetic factors to the LHON phenotype.
The study aimed to estimate the cut-off value for homeostatic model assessment for insulin resistance (HOMA-IR) discriminating the insulin resistance based on the sex hormones binding globulin (SHBG) ...level in women with polycystic ovary syndrome (PCOS).
Data from medical records of 854 Caucasian women diagnosed with PCOS were analyzed. Anthropometric data, fasting plasma glucose, insulin and SHBG levels were measured. HOMA-IR was calculated with a standard formula. The cut-off value was calculated using receiver-operating characteristics.
Circulating SHBG levels below the normal range (26.1 nmol/L) were found in 25.4% of study participants. This subgroup had a significantly higher BMI, fasting glucose and insulin concentrations and HOMA-IR values. Empirical optimal cut-off values for HOMA-IR corresponding to low SHBG levels was ≥2.1 area under the curve (AUC) 0.73, accuracy 0.65, sensitivity 72.3%, specificity 63.1%, positive predictive value (PPV) 40.0%, negative predictive value (NPV) 87.0%.
Our study suggests that the cut-off point for HOMA-IR discriminating the insulin resistance based on the SHBG level, in young Caucasian women with polycystic ovary syndrome is 2.1, and is consistent with the cut-off value adopted by the European Group for the Study of Insulin Resistance (above 2.0).
Splenic artery aneurysm (SAAs) rupture is associated with a high mortality rate. Regular surveillance with imaging before and after intervention is crucial to guide best evidence treatment. The ...following study aimed to determine the efficacy of color Doppler ultrasound imaging (DUS) compared to digital subtraction angiography (DSA) and magnetic resonance angiography (MRA) as a follow-up modality after selective coil embolization of true SAAs. We analyzed data from 20 patients, 15 females (48.1 ± 16.1 years) undergoing selective SAA coil embolization using detachable fibered embolization coils. Imaging using DUS, MRA, and DSA was performed 3 months after the initial embolization or the consequent re-embolization procedure. Primary clinical success, defined as Class I aneurysm occlusion, on 3-month follow-up was seen in 16 (80.0%) patients. DUS had a sensitivity of 94.4% and a specificity of 42.9% when compared to DSA and 92.3% and 30%, respectively, when compared to MRA in identifying Class I aneurysm occlusion. The positive predictive value (PPV) of DUS in identifying the need for re-embolization was 75.0%, while the NPV of DUS in these terms was 90.5%. DUS showed a high sensitivity in detecting aneurysm occlusion and clinical success, simultaneously exhibiting poor specificity. Still, with caution, this follow-up modality could be used for monitoring select low-risk patients after selective embolization of SAAs. DUS could provide a higher cost-to-benefit ratio, enabling more systematic post-procedural follow-up, as it is far more commonly used compared to MRA and non-invasive compared to DSA.
Leber hereditary optic neuropathy (LHON) is a genetic, maternally inherited disease caused by point mutations in the mitochondrial genome. LHON patients present with sudden, painless and usually ...bilateral loss of vision caused by optic nerve atrophy. The first clinical description of the disease was made by Theodor Leber, a German ophthalmologist, in 1871. Here we present his thorough notes about members of four families and their pedigrees. We also provide insights into the current knowledge about LHON pathology, genetics and treatment in comparison with Leber's findings.
•The first description of Leber hereditary optic neuropathy from 1871 is presented.•We constructed pedigrees for four families based on Theodor Leber's case report.•Leber's findings provided the basis for the present-day knowledge of the disease.•We present the current knowledge about LHON genetics and treatment.
Mitochondrial encephalomyopathies comprise a group of heterogeneous disorders resulting from impaired oxidative phosphorylation (OxPhos). Among a variety of symptoms progressive external ...ophthalmoplegia (PEO) seems to be the most common. The aim of this study is to present clinical and genetic characteristics of Polish patients with PEO. Clinical, electrophysiological, neuroradiological, and morphological data of 84 patients were analyzed. Genetic studies of mitochondrial DNA (mtDNA) were performed in all patients. Among nuclear DNA (nDNA) genes
was sequenced in 41 patients,
(
) in 13 patients, and
in 2 patients. Total of 27 patients were included in the chronic progressive external ophthalmoplegia (CPEO) group, 24 in the CPEO+ group. Twenty-six patients had mitochondrial encephalomyopathy (ME), six patients Kearns-Sayre syndrome (KSS), and one patient sensory ataxic neuropathy, dysarthria, ophthalmoparesis (SANDO) syndrome. Genetic analysis of nDNA genes revealed the presence of pathogenic or possibly pathogenic variants in the
gene in nine patients, the
gene in five patients and the
gene in two patients. Detailed patients' history and careful assessment of family history are essential in the diagnostic work-up. Genetic studies of both mtDNA and nDNA are necessary for the final diagnosis of progressive external ophthalmoplegia and for genetic counseling.
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