Simple Summary Gliobastoma is one of the deadliest tumors overall, yet the most common malignant brain tumor. The new World Health Organization Classification of Brain Tumors brought changes in how we look at this type of malignancy. Now we know that glioblastoma is rather a spectrum of similar tumors, but with some distinct characteristics that include molecular footprint, response to therapy and with that overall survival, among others. We hypothesised that by employing phosphorous magnetic resonance we will be able to show differences in cellular energy metabolism in these various subtypes of glioblastoma. For example, we found indices of faster cell reproduction and tumor growth in MGMT-methylated and EGFR-amplified tumors. These tumors also could have reduced energetic state or tissue oxygenation due to the increased necrosis. Tumors with EGFR-amplification could have increased apoptotic activity regardless of their MGMT status. Our study indicated various differences in energetic metabolism in tumors with different molecular characteristics, which could potentially be important in future therapeutic strategies. Abstract The World Health Organisation’s (WHO) classification of brain tumors requires consideration of both histological appearance and molecular characteristics. Possible differences in brain energy metabolism could be important in designing future therapeutic strategies. Forty-three patients with primary, isocitrate dehydrogenase 1 (IDH1) wild type glioblastomas (GBMs) were included in this study. Pre-operative standard MRI was obtained with additional phosphorous magnetic resonance spectroscopy (31-P-MRS) imaging. Following microsurgical resection of the tumors, biopsy specimens underwent neuropathological diagnostics including standard molecular diagnosis. The spectroscopy results were correlated with epidermal growth factor (EGFR) and O6-Methylguanine-DNA methyltransferase (MGMT) status. EGFR amplified tumors had significantly lower phosphocreatine (PCr) to adenosine triphosphate (ATP)-PCr/ATP and PCr to inorganic phosphate (Pi)-PCr/Pi ratios, and higher Pi/ATP and phosphomonoesters (PME) to phosphodiesters (PDE)-PME/PDE ratio than those without the amplification. Patients with MGMT-methylated tumors had significantly higher cerebral magnesium (Mg) values and PME/PDE ratio, while their PCr/ATP and PCr/Pi ratios were lower than in patients without the methylation. In survival analysis, not-EGFR-amplified, MGMT-methylated GBMs showed the longest survival. This group had lower PCr/Pi ratio when compared to MGMT-methylated, EGFR-amplified group. PCr/Pi ratio was lower also when compared to the MGMT-unmethylated, EGFR not-amplified group, while PCr/ATP ratio was lower than all other examined groups. Differences in energy metabolism in various molecular subtypes of wild-type-GBMs could be important information in future precision medicine approach.

Emerging sets of single-cell sequencing data makes it appealing to apply existing tumor phylogeny reconstruction methods to analyze associated intratumor heterogeneity. Unfortunately, tumor phylogeny inference is an NP-hard problem and existing principled methods typically fail to scale up to handle thousands of cells and mutations observed in emerging single-cell data sets. Even though there are greedy heuristics to build hierarchical clustering of cells and mutations, they suffer from well-documented issues in accuracy. Additionally even when “optimal” solutions are feasible, existing approaches only provide a single “most likely” tree to depict the evolutionary processes that may result in an observed collection of cells and mutations. To make matters worse, the vast majority of single-cell sequencing data sets are transcriptomic and as a result, suffer from considerable variation in coverage across mutational loci. In this paper, we introduce Trisicell, a computational toolkit for scalable tumor phylogeny reconstruction and validation from single-cell genomic, exomic or transcriptomic sequencing data. Trisicell has three components: (i) Trisicell-DnC, a new tumor phylogeny reconstruction method from genotype matrices derived from single-cell data, (ii) Trisicell-ConT a new algorithm for constructing the consensus for two or more tumor phylogenies - which may be built through the use of different data types on the same set of cells, or built through the use of different methods on the same data, and (iii) Trisicell-PF, a new partition function method for assessing the likelihood of any user-defined subtree/set of cells to be seeded by a given set of mutations in the phylogeny. Collectively, these tools provide means of identifying and validating robust portions of a tumor phylogeny, offering the ability to focus on the most important (sub)clones and the genomic alterations that seed the associated clonal expansion. We applied Trisicell to a panel of clonal sublines derived from single-cells of a parental mouse melanoma model on which we performed both whole exome and whole transcriptome sequencing. The tumor phylogenies of the clonal sublines built on exomic and transcriptomic mutations by Trisicell-DnC, were shown by Trisicell-ConT to be highly similar and the subtrees comprised of phenotypically similar clonal sublines were shown to be strongly associated by Trisicell-PF to their seeding mutations. In addition, we applied Trisicell to single-cell whole transcriptome sequencing data from a tumor derived from the same parental melanoma cell line, which was subjected to anti-CTLA-4 immunotherapy. The phylogenies generated from both studies featured distinct subtrees, strongly associated with phenotypes including cell differentiation status, tumor growth and therapeutic response. These results suggest that Trisicell can be used for scalable tumor phylogeny reconstruction and validation through both single-cell and clonal-subline sequencing data, which may reveal strong phenotypic associations. In particular, they suggest that the developmental status and phenotypic intratumoral heterogeneity of melanoma originates from observable subclonal variation. Citation Format: Farid Rashidi Mehrabadi, Salem Malikic, Kerrie L. Marie, Eva Perez-Guijarro, Erfan Sadeqi Azer, Howard H. Yang, Can Kizilkale, Charli Gruen, Huaitian Liu, Christina Marcelus, Aydin Buluc, Funda Ergun, Maxwell P. Lee, Glenn Merlino, Chi-Ping Day, S. Cenk Sahinalp. Trisicell: Scalable Tumor Phylogeny Reconstruction and Validation Reveals Developmental Origin and Therapeutic Impact of Intratumoral Heterogeneity [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2021; 2021 Apr 10-15 and May 17-21. Philadelphia (PA): AACR; Cancer Res 2021;81(13_Suppl):Abstract nr LB019.

Background: Novel temporal-spatial features of the 12-lead ECG can conceptually optimize culprit lesions’ detection beyond that of classical ST amplitude measurements. We sought to develop a data-driven approach for ECG feature selection to build a clinically relevant algorithm for real-time detection of culprit lesion. Methods: This was a prospective observational cohort study of chest pain patients transported by emergency medical services to three tertiary care hospitals in the US. We obtained raw 10-s, 12-lead ECGs (500 s/s, HeartStart MRx, Philips Healthcare) during prehospital transport and followed patients 30 days after the encounter to adjudicate clinical outcomes. A total of 557 global and lead-specific features of P-QRS-T waveform were harvested from the representative average beats. We used Recursive Feature Elimination and LASSO to identify 35/557, 29/557, and 51/557 most recurrent and important features for LAD, LCX, and RCA culprits, respectively. Using the union of these features, we built a random forest classifier with 10-fold cross-validation to predict the presence or absence of culprit lesions. We compared this model to the performance of a rule-based commercial proprietary software (Philips DXL ECG Algorithm). Results: Our sample included 2400 patients (age 59 ± 16, 47% female, 41% Black, 10.7% culprit lesions). The area under the ROC curves of our random forest classifier was 0.85 ± 0.03 with sensitivity, specificity, and negative predictive value of 71.1%, 84.7%, and 96.1%. This outperformed the accuracy of the automated interpretation software of 37.2%, 95.6%, and 92.7%, respectively, and corresponded to a net reclassification improvement index of 23.6%. Metrics of ST80; Tpeak-Tend; spatial angle between QRS and T vectors; PCA ratio of STT waveform; T axis; and QRS waveform characteristics played a significant role in this incremental gain in performance. Conclusions: Novel computational features of the 12-lead ECG can be used to build clinically relevant machine learning-based classifiers to detect culprit lesions, which has important clinical implications.

This paper presents a fuzzy system for reliability-based power distribution network planning. The proposed Mamdani type fuzzy inference system with subsequent application of the Bellman-Zadeh decision-making method is used to evaluate the reliability of the power line feeders as criteria for power system planning. Unplanned outages of system components, the Energy Not Supplied (ENS) and age of the power lines are used as input variables of the system and are fuzzified using triangular fuzzy functions. The proposed model was tested on a model of a realistic distribution network in order to prove its relevance and applicability. Results demonstrated that this model could make a contribution in this field as it can be used in practical planning situations for project priority ranking.

In this paper, the polyphenol content and antioxidant activity of fig leaf extracts were analyzed. Extraction was performed with methanol, ethanol, acetone and their aqueous mixtures (50:50 v/v). Extractions were performed with stirring at 300 rpm on a vibromix and ultrasonic bath for 15 minutes. The polyphenol content was determined spectrophotometrically using the Folin-Ciocalteu test. Antioxidant capacity was tested using the FRAP and DPPH methods. The results showed a significant effect of extraction of bioactive components using an organic solvent:water mixture in relation to the organic solvent itself. Ultrasonic extraction proved to be a more efficient technique compared to mixing at 300 rpm.  

Abstract C18H12Br2CuN4O2, monoclinic, P21/c (no. 14), a = 11.5165(11) Å, b = 5.4369(5) Å, c = 14.4872(14) Å, V = 873.52(14) Å3, Z = 2, R gt (F) = 0.0232, wR ref (F2) = 0.0559, T = 200 K.

The aim of this study was to determine the antioxidant capacity of some phytochemicals by using an H2O2 scavenging assay. Betaine, Allantoin and Nicotinamide were put to the test.  Even though hydrogen peroxide (H2O2) is not intrinsically reactive, it can be transformed into the extremely reactive and harmful hydroxyl radical (HO), which is then able to interact with nucleotides in deoxyribose nucleic acid and in that way trigger breakage of the strand resulting in carcinogenesis, mutagenesis, etc. Antioxidants aid in the protection of cells from the harmful effects of reactive oxygen species that are known to induce oxidative stress. Excessive production of these reactive oxygen species in the human body is associated with many chronic degenerative diseases such as diabetes, neurodegenerative disease, cancer, etc. The effective way to minimize levels of oxidative stress is the ability to scavenge these reactive oxygen species (ROS). Also, phytochemicals are able to act as antioxidants, and in that way play a vital role in the prevention of disease caused by oxidative stress. The ability of a compound to scavenge H2O2 is a good predictor of its potential antioxidant function. The hydrogen peroxide (H2O2) scavenging assay was determined using the Ruch et al., 1989 method, and a UV-VIS spectrophotometer. In conclusion, our samples had marvellous H2O2 scavenging activity and possessed good antioxidant capability, and were compared with the ascorbic acid (vitamin c) as standard natural antioxidant/ as reference antioxidant. The samples were also able to scavenge H2O2 in a concentration-dependent way, according to our results

The relationship between education and labor market is significant and complex. Education increases employment opportunities and reduces the chance of occurrence and duration of unemployment. Earnings, among other things, represent private returns on investment in education and are in the center of the analysis of this article. The main aim of this article is to estimate private and social returns on investment in primary, secondary and tertiary education in selected old and new member states of the European Union (EU) by using two methods (Earnings function and Short-cut method) based on the Mincer equation. Results have shown that there is no statistically significant difference between the estimated private and social returns on investment in primary, secondary and tertiary education in groups of old and new EU members. New members converge towards the old members, at least when it comes to returns on investment in these three education levels. The results also indicate the existence of low and negative returns on investment in education in both old and new EU members. Thus, this article with its new findings contributes significantly to the literature that studies the universality of conclusions on returns on investment in education and the methodology that is used.

Debljina kore i njen udio u obujmu oblog drva predstavljaju bitne značajke u tehnološkom procesu pridobivanja drva, posebno u fazi preuzimanja drva. S obzirom da je itekako važno raspolagati s relativno točnim podacima ovih značajki kore za pojedine vrste drveća, osnovni cilj ovoga rada je istražiti navedene značajke kore bukve. Istraživanje je provedeno na području Kantona 10, a obuhvatilo je 678 stabla bukve od 10 do 85 cm promjera na prsnoj visini i od 5 do 40 m visine. Mjerenje srednjeg promjera i debljine kore obavljeno je metodom sekcioniranja, a ukupno je izmjereno 6.403 promjera i debljina kore ili 9,4 mjerenja po jednom stablu u prosjeku. Rezultati su pokazali sljedeće: a) povećanjem srednjeg promjera oblog drva dvostruka debljina kore povećava se od 6,05 mm (debljinski razred 12,5 cm) do 20,69 mm (debljinski razred 82,5 cm); b) povećanjem srednjeg promjera oblog drva udio se kore u obujmu eksponencijalno smanjuje od 9,44% (debljinski razred 12,5 cm) do 4,95% (debljinski razred 82,5 cm). ­Utvrđene razlike u komparaciji s drugim autorima koji su istraživali ove značajke kore bukve, ukazuju na važnost nastavka istraživanja i na drugim područjima u BiH. Na taj način bi se dobili pouzdaniji rezultati koji bi bili primjenjivi za cijelu državu ili parcijalno za pojedine njene dijelove, ako se razlika između područja pokaže statistički ­značajnom. Dobiveni rezultati predstavljaju nezaobilaznu polaznu osnovu za izradu tablica kore bukve i novog ­pravilnika o načinu izmjere oblog drva i utvrđivanja količina.

Heavy metals, due to their inability to degrade, pose a serious environmental and nutritional problem. The accumulation of essential and non-essential heavy metals in living organisms reduces normal growth and development, resulting in acute poisoning, disease and even death of organisms. Melatonin is a very important multifunctional molecule in protecting plants from oxidative stress due to its ability to directly neutralize reactive oxygen species (ROS). Also, melatonin has a chelating property, which may contribute in reducing metal-induced toxicity. In this paper, the protective role of melatonin in counteracting metal-induced free radical generation was highlighted. Using the HPLC-FLD technique melatonin was identified and quantified in the roots and leaves of lemon balm ( Melissa officinalis L.), grown under photoperiod conditions. Furthermore, the response of plants pre-treated with exogenous 0.1 mM melatonin to the increased zinc (Zn) and cadmium (Cd) concentrations was observed, with changes in mineral (Ca, Mg), physiological and antioxidant status of the plant during heavy metals stress. The obtained melatonin concentrations were the highest published for dry plants so far. Elevated Cd and Zn levels in soil caused alternation in biochemical and physiological parameters of lemon balm leaves and roots. However, melatonin pre-treatment increased plant tolerance to heavy metals stress. Increased Cd and Zn uptake and their translocation into the leaves were also improved, indicating the possible use of melatonin in phytoremediation.

<p style="text-align: justify;">Microstructure of an austenitic stainless steels is primarily monophasic, i.e. austenitic. However, the chemical composition of steel can affect on precipitation of a delta ferrite. The presence of the delta ferrite in austenitic stainless steel has a beneficial or detrimental effect on mechanical properties (impact and tensile) as well as on weldability and corrosion resistance. This paper presents some methods of determining the content of delta ferrite in austenitic stainless steels as well as in weld metal.</p>

The contemporary business environment, characterized by high levels of dynamism, turbulence, and uncertainty, has forced companies to re-evaluate traditional models of commerce and make a shift towards Internet-based e-commerce models. Since the perception of usefulness determines the firm’s willingness to adopt e-commerce, this study strives to explore the contributing factors among SMEs in Bosnia and Herzegovina. A survey of 154 SME managers/owners was conducted, to identify variables that are key drivers of perceived usefulness. The findings revealed that the strategic management benefits, compatibility, and external pressures are the key predictors of perceived usefulness. This study also shows that the perceived usefulness of e-commerce is higher, if companies belonging to the same industry, or the same business network, have already adopted this business model. These findings strengthen the idea of the enterprise bandwagon effect. Compared to the newer and younger firms, the results also indicate that mature firms tend to have higher perceived usefulness of e-commerce.

Takayasu arteritis (TA) is a challenging chronic inflammatory vasculitis of large vessels with unknown etiology. It usually affects the aorta and its main branches and in few cases it affects other arteries like pulmonary and coronary. We report a case of a young woman with transient ischemic attack (TIA) as the initial presentation followed later by ischemic limb syndrome and then ischemic stroke. Lack of specific diagnostic biomarkers for this disease makes early diagnosis and treatment challenging.