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Yusuf Baran,1 Guray Saydam21Department of Molecular Biology and Genetics, Izmir Institute of Technology, Izmir, Turkey; 2Department of Hematology, School of Medicine, Ege University, Izmir, TurkeyAbstract: Chronic myeloid leukemia (CML) is a malignant disease that originates in the bone marrow and is designated by the presence of the Philadelphia (Ph+) chromosome, a translocation between chromosomes 9 and 22. Targeted therapy against CML commenced with the development of small-molecule tyrosine kinase inhibitors (TKIs) exerting their effect against the oncogenic breakpoint cluster region (BCR)-ABL fusion protein. Imatinib emerged as the first successful example of a TKI used for the treatment of chronic-phase CML patients and resulted in significant improvements in response rate and overall survival compared with previous treatments. However, a significant portion of patients failed to respond to the therapy and developed resistance against imatinib. Second-generation TKIs nilotinib and dasatinib were to have higher efficiency in clinical trials in imatinib- resistant or intolerant CML patients compared with imatinib. Identification of novel strategies such as dose escalation, drug combination therapy, and use of novel BCR-ABL inhibitors may eventually overcome resistance against BCR-ABL TKIs. This article reviews the history of CML, including the treatment strategies used prediscovery of TKIs and the preclinical and clinical data obtained after the use of imatinib, and the second-generation TKIs developed for the treatment of CML.Keywords: drug resistance, tyrosine kinase inhibitors, chronic myeloid leukemia, imatinib, BCR/ABL

Abstract Objective The primary objective of this study was to identify the risk of metastasis to lymph nodes above the inferior mesenteric artery (IMA) in endometrioid-type endometrial cancer (EC) and the factors that influence metastasis. Methods The study included patients who had been operated on for endometrioid-type EC in three gynecological oncology centers between 2007 and 2023. The supramesenteric lymph node (SM-LN) is the region between the left renal vein and the IMA, whereas the inframesenteric lymph node (IM-LN) is the region between the IMA and the aortic bifurcation, as determined by the level of the IMA. Results The study sample comprised 412 patients. The median number of lymph nodes excised per patient was 58. The median count was 37 for pelvic lymph nodes, 21 for para-aortic lymph nodes, 8 for IM-LN, and 13 for SM-LN. In the univariate analysis, the factors that were found to be statistically significant in determining SM-LN metastasis included tumor size, depth of myometrial invasion, uterine serosal invasion, lymphovascular space invasion (LVSI), cervical invasion, peritoneal cytology, adnexal metastasis, omental metastasis, non-nodal extrauterine metastasis, pelvic lymph node metastasis, and IM-LN metastasis. In the multivariate analysis, SM-LN metastasis was independently associated with tumor size, LVSI, pelvic lymph node metastasis, and IM-LN metastasis. Conclusion In conclusion, in cases of intermediate-high risk EC, it is important to know that the disease spreads to SM-LN in 7.3% of patients. The efficacy of postoperative adjuvant treatment may be inadequate due to a lack of information regarding the SM-LN region.

Background and Objective: This study aimed to investigate the relationship between tramadol use and cardio electrophysiological imbalance (iCEB/iCEBc) in general surgery patients with complaints of acute postoperative pain (APP). Materials and Methods: In this prospective cross-sectional study, a total of 218 consecutive patients over the age of 18, who underwent surgical procedures in our clinic (postoperative), were included. For analgesic effect, tramadol was administered with an initial total max dose not exceeding 2 mg/kg. A single max dose (100 mg) was given intravenously, infused in 100 cc of saline over 60 min. In all patients requiring analgesia, electrocardiography (ECG) was performed in the supine position with 12 leads at 25 mm/s and 10 mm/mV, immediately before and after tramadol administration. iCEB was calculated as QT/QRS and iCEBc as QTc/QRS. Results: A total of 218 patients were included in this study, with 98 of them being male (45%) and the average age being 46.20 ± 17.19 years. The average tramadol dose for analgesic effect was 98.21 ± 7.62 mg. The QT interval (339.17 ± 36.27 vs. 349.88 ± 30.86, p = 0.001), QTc interval (407.07 ± 26.36 vs. 419.64 ± 31.78, p < 0.001), QRS duration (80.82 ± 11.39 vs. 78.57 ± 9.80, p = 0.018), iCEB (4.26 ± 0.69 vs. 4.52 ± 0.70, p < 0.001), and iCEBc (5.14 ± 0.86 vs. 5.42 ± 0.79, p = 0.001) values significantly increased compared to the baseline immediately after drug administration. Furthermore, the drug dose was identified as an independent predictor that increased iCEBc (β = 0.201, p = 0.003). Conclusions: Even at single and therapeutic doses, tramadol increases iCEB and iCEBc. Additionally, the drug dose is an independent predictor of increased iCEBc.

Electric Vehicles (EVs) are a rapidly growing technology which can lower greenhouse-gas emissions in the transport and energy sectors. The EV batteries can discharge the stored energy back to grid, also known as Vehicle-to-Grid (V2G) which can support the integration of variable distributed renewable generation. Previous research identified financial barriers to the implementation of V2G, however, recent advancements in battery technology present new opportunities to make V2G technology viable. Using the current and predicted EV technology trends, this paper evaluates the annual operation and benefits of EVs and V2G in a microgrid environment and demonstrates different modes of operation. Guided by the gaps identified in the literature, one of the main contributions of this research is to uncover the impact of EV charging scenarios on the V2G operations. Furthermore, the research reveals the interactions between V2G and variable renewable generation coupled with utility scale battery over yearlong simulations to assess seasonal characteristics of V2G operations, which was mostly unexplored to date. Simulation results indicate that the operation of V2G in an optimised microgrid environment improves the economic operation of the system and reduces the levelized cost of electricity by up to 5.7%. Additionally, V2G provides more benefit to grids with higher solar generation proportion The results suggest that the latest advancements in EV technology have improved the economic viability of V2G as well as its potential to improve grid efficiency through providing additional storage capacity and peak demand management.

Electronic decision-support tools are becoming an essential component of government strategies to tackle non-native species invasions. This study describes the development and application of a multilingual electronic decision-support tool for screening terrestrial animals under current and future climate conditions: the Terrestrial Animal Species Invasiveness Screening Kit (TAS-ISK). As an adaptation of the widely employed Aquatic Species Invasiveness Screening Kit (AS-ISK), the TAS-ISK question template inherits from the original Weed Risk Assessment (WRA) and related WRA-type toolkits and complies with the ‘minimum requirements’ for use with the recent European Regulation on invasive alien species of concern. The TAS-ISK consists of 49 basic questions on the species’ biogeographical/historical traits and its biological/ecological interactions, and of 6 additional questions to predict how climate change is likely to influence the risks of introduction, establishment, dispersal and impact of the screened species. Following a description of the main features of this decision-support tool as a turnkey software application and of its graphical user interface with support for 32 languages, sample screenings are provided in different risk assessment areas for one representative species of each of the main taxonomic groups of terrestrial animals supported by the toolkit: mammals, birds, reptiles, amphibians, annelids, insects, molluscs, nematodes, and platyhelminths. The highest-scoring species were the red earthworm Lumbricus rubellus for the Aegean region of Turkey and the New Zealand flatworm Arthurdendyus triangulatus for Croatia. It is anticipated that adoption of this toolkit will mirror that of the worldwide employed AS-ISK, hence allowing to share information and inform decisions for the prevention of entry and/or dispersal of (high-risk) non-native terrestrial animal species – a crucial step to implement early-stage control and eradication measures as part of rapid-response strategies to counteract biological invasions.

There are many types of neoplasms in or around the foramen of Luschka (FL), and definitive diagnosis in some cases requires knowledge of imaging findings. The uncommon and challenging neoplasms with FL involvement considered in this study are exophytic brainstem glioma, primary glioblastoma of the cerebellopontine angle (CPA), primary anaplastic ependymoma of the CPA, choroid plexus papilloma of the FL, solitary FL choroid plexus metastasis, extraskeletal myxoid chondrosarcoma of the jugular foramen, paraganglioma of the jugular foramen, exostosis of the jugular foramen, psammomatous meningioma in the lateral cerebellar medullary cistern, epidermoid tumor of the fourth ventricle, and a hypoglossal schwannoma. These neoplasms may have overlapping clinical and imaging features, but some have relatively distinct imaging features. Knowledge of the key clinical and magnetic resonance imaging features of these unusual lesions with FL involvement is important for radiologists to improve diagnostic ability and to assist the referring physician in the appropriate management of the patient.

Material selection is a crucial aspect in the design of reliable, efficient and long-lasting wave energy converters (WECs). However, to date, the development of tailored methodologies applied to the material selection of WECs remains vastly unexplored. In this paper, a material selection framework for the case of lift-based WECs is developed. The application of the methodology is demonstrated with the hydrofoils of the device. Offshore steel, high-strength offshore steel, aluminium alloys, and carbon- and glass-fibre-reinforced composites are considered and evaluated subject to relevant criteria for wave energy converters, namely structural reliability, hydrodynamic efficiency, offshore maintainability, total manufacturing cost and environmental impact. Candidate materials are assessed via fuzzy TOPSIS for three scenarios of the life cycle of the WEC: conceptual, commercial and future projection stages. Results show that the choice of optimal materials could change from present to future and that multi-criteria decision-making tools aided by a fuzzy approach are useful design tools for novel WECs when field data are scarce. Hence, methodologies such as the ones presented in this work can help in reducing the probability of mechanical failures of emerging WEC technology.

The present study aims to develop a risk-based approach to finding optimal solutions for life extension management for offshore wind farms based on Markowitz’s modern portfolio theory, adapted from finance. The developed risk-based approach assumes that the offshore wind turbines (OWT) can be considered as cash-producing tangible assets providing a positive return from the initial investment (capital) with a given risk attaining the targeted (expected) return. In this regard, the present study performs a techno-economic life extension analysis within the scope of the multi-objective optimisation problem. The first objective is to maximise the return from the overall wind assets and the second objective is to minimise the risk associated with obtaining the return. In formulating the multi-dimensional optimisation problem, the life extension assessment considers the results of a detailed structural integrity analysis, a free-cash-flow analysis, the probability of project failure, and local and global economic constraints. Further, the risk is identified as the variance from the expected mean of return on investment. The risk–return diagram is utilised to classify the OWTs of different classes using an unsupervised machine learning algorithm. The optimal portfolios for the various required rates of return are recommended for different stages of life extension.

Lake Van is the largest saline soda lake in the world and one of the world’s few endorheic lakes of greater than 3,000 km2 surface area. Despite its huge size, no fish species have so far been known to permanently occur in this lake due to its extreme environmental conditions. Here, we report the discovery of a fish population that permanently inhabits some of the unique microbialites of the lake, at a maximum depth of 13 m and about 500 m offshore. We tested whether this is an undescribed species or a new occurrence of a known species. A molecular and morphological examination showed that the newly discovered fish represents an isolated population of Oxynoemacheilus ercisianus, the only nemacheilid loach native to the freshwater tributaries of the Lake Van endorheic basin. Our further hypotheses on the prediction that (a) stream fishes would have a more anterior placement of fins than lake fishes were supported; but, that (b) stream fishes would be more slender bodied than their lake conspecifics was not supported. The lake dwelling population also shows very small sequence divergence (0.5% K2P distance) to its stream dwelling conspecific in the mtDNA-COI barcode region. The notable morphological difference with minute molecular divergence implies that the newly discovered population might have lost its link to freshwater during desiccation and transgressional phases of the Lake Van, and has adapted to a life on the microbialites.