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J. Panić, M. Vraneš, Janja Mirtič, R. C. Korošec, Špela Zupančič, S. Gadžurić, J. Kristl, M. B. Rogač

Orion Eduard Heinz Elena Oleg Diane Kris Devleta Sanja I Gliozheni Hambartsoumian Strohmer Petrovskaya Tish, O. Gliozheni, E. Hambartsoumian, H. Strohmer, E. Petrovskaya, O. Tishkevich, D. De Neubourg, K. Bogaerts et al.

Abstract STUDY QUESTION What are the data and trends on ART and IUI cycle numbers and their outcomes, and on fertility preservation (FP) interventions, reported in 2018 as compared to previous years? SUMMARY ANSWER The 22nd ESHRE report shows a continued increase in reported numbers of ART treatment cycles and children born in Europe, a decrease in transfers with more than one embryo with a further reduction of twin delivery rates (DRs) as compared to 2017, higher DRs per transfer after fresh IVF or ICSI cycles (without considering freeze-all cycles) than after frozen embryo transfer (FET) with higher pregnancy rates (PRs) after FET and the number of reported IUI cycles decreased while their PR and DR remained stable. WHAT IS KNOWN ALREADY ART aggregated data generated by national registries, clinics or professional societies have been gathered and analysed by the European IVF-monitoring Consortium (EIM) since 1997 and reported in 21 manuscripts published in Human Reproduction and Human Reproduction Open. STUDY DESIGN, SIZE, DURATION Data on medically assisted reproduction (MAR) from European countries are collected by EIM for ESHRE on a yearly basis. The data on treatment cycles performed between 1 January and 31 December 2018 were provided by either national registries or registries based on initiatives of medical associations and scientific organizations or committed persons of 39 countries. PARTICIPANTS/MATERIALS, SETTING, METHODS Overall, 1422 clinics offering ART services in 39 countries reported a total of more than 1 million (1 007 598) treatment cycles for the first time, including 162 837 with IVF, 400 375 with ICSI, 309 475 with FET, 48 294 with preimplantation genetic testing, 80 641 with egg donation (ED), 532 with IVM of oocytes and 5444 cycles with frozen oocyte replacement (FOR). A total of 1271 institutions reported data on IUI cycles using either husband/partner’s semen (IUI-H; n = 148 143) or donor semen (IUI-D; n = 50 609) in 31 countries and 25 countries, respectively. Sixteen countries reported 20 994 interventions in pre- and post-pubertal patients for FP including oocyte, ovarian tissue, semen and testicular tissue banking. MAIN RESULTS AND THE ROLE OF CHANCE In 21 countries (21 in 2017) in which all ART clinics reported to the registry, 410 190 treatment cycles were registered for a total population of ∼ 300 million inhabitants, allowing a best estimate of a mean of 1433 cycles performed per million inhabitants (range: 641–3549). Among the 39 reporting countries, for IVF, the clinical PR per aspiration slightly decreased while the PR per transfer remained similar compared to 2017 (25.5% and 34.1% in 2018 versus 26.8% and 34.3% in 2017). In ICSI, the corresponding rates showed similar evolutions in 2018 compared to 2017 (22.5% and 32.1% in 2018 versus 24.0% and 33.5% in 2017). When freeze-all cycles were not considered for the calculations, the clinical PRs per aspiration were 28.8% (29.4% in 2017) and 27.3% (27.3% in 2017) for IVF and ICSI, respectively. After FET with embryos originating from own eggs, the PR per thawing was 33.4% (versus 30.2% in 2017), and with embryos originating from donated eggs 41.8% (41.1% in 2017). After ED, the PR per fresh embryo transfer was 49.6% (49.2% in 2017) and per FOR 44.9% (43.3% in 2017). In IVF and ICSI together, the trend towards the transfer of fewer embryos continues with the transfer of 1, 2, 3 and ≥4 embryos in 50.7%, 45.1%, 3.9% and 0.3% of all treatments, respectively (corresponding to 46.0%, 49.2%. 4.5% and 0.3% in 2017). This resulted in a reduced proportion of twin DRs of 12.4% (14.2% in 2017) and similar triplet DR of 0.2%. Treatments with FET in 2018 resulted in twin and triplet DRs of 9.4% and 0.1%, respectively (versus 11.2% and 0.2%, respectively in 2017). After IUI, the DRs remained similar at 8.8% after IUI-H (8.7% in 2017) and at 12.6% after IUI-D (12.4% in 2017). Twin and triplet DRs after IUI-H were 8.4% and 0.3%, respectively (in 2017: 8.1% and 0.3%), and 6.4% and 0.2% after IUI-D (in 2017: 6.9% and 0.2%). Among 20 994 FP interventions in 16 countries (18 888 in 13 countries in 2017), cryopreservation of ejaculated sperm (n = 10 503, versus 11 112 in 2017) and of oocytes (n = 9123 versus 6588 in 2017) were the most frequently reported. LIMITATIONS, REASONS FOR CAUTION The results should be interpreted with caution as data collection systems and completeness of reporting vary among European countries. Some countries were unable to deliver data about the number of initiated cycles and/or deliveries. WIDER IMPLICATIONS OF THE FINDINGS The 22nd ESHRE data collection on ART, IUI and FP interventions shows a continuous increase of reported treatment numbers and MAR-derived livebirths in Europe. Although it is the largest data collection on MAR in Europe, further efforts towards optimization of both the collection and reporting, with the aim of improving surveillance and vigilance in the field of reproductive medicine, are awaited. STUDY FUNDING/COMPETING INTEREST(S) The study has received no external funding and all costs are covered by ESHRE. There are no competing interests.

X. Castro Dopico, S. Muschiol, N. Grinberg, S. Aleman, D. Sheward, L. Hanke, M. Ahl, Linnéa Vikström et al.

Population‐level measures of seropositivity are critical for understanding the epidemiology of an emerging pathogen, yet most antibody tests apply a strict cutoff for seropositivity that is not learnt in a data‐driven manner, leading to uncertainty when classifying low‐titer responses. To improve upon this, we evaluated cutoff‐independent methods for their ability to assign likelihood of SARS‐CoV‐2 seropositivity to individual samples.

N. V. Srikanth Vallabani, Andi Alijagic, Alexander Persson, I. Odnevall, E. Särndahl, H. Karlsson

Additive manufacturing (AM) or "3D-printing" is a ground-breaking technology that enables the production of complex 3D parts. Its rapid growth calls for immediate toxicological investigations of possible human exposures in order to estimate occupational health risks. Several laser-based powder bed fusion AM techniques are available of which many use metal powder in the micrometer range as feedstock. Large energy input from the laser on metal powders generates several by-products, like spatter and condensate particles. Due to often altered physicochemical properties and composition, spatter and condensate particles can result in different toxicological responses compared to the original powder particles. The toxicity of such particles has, however, not yet been investigated. The aim of the present study was to investigate the toxicity of condensate/spatter particles formed and collected upon selective laser melting (SLM) printing of metal alloy powders, including a nickel-chromium-based superalloy (IN939), a nickel-based alloy (Hastelloy X, HX), a high-strength maraging steel (18Ni300), a stainless steel (316 L), and a titanium alloy (Ti6Al4V). Toxicological endpoints investigated included cytotoxicity, generation of reactive oxygen species (ROS), genotoxicity (comet and micronucleus formation), and inflammatory response (cytokine/chemokine profiling) following exposure of human bronchial epithelial cells (HBEC) or monocytes/macrophages (THP-1). The results showed no or minor cytotoxicity in the doses tested (10-100 μg/mL). Furthermore, no ROS generation or formation of micronucleus was observed in the HBEC cells. However, an increase in DNA strand breaks (detected by comet assay) was noted in cells exposed to HX, IN939, and Ti6Al4V, whereas no evident release of pro-inflammatory cytokine was observed from macrophages. Particle and surface characterization showed agglomeration in solution and different surface oxide compositions compared to the nominal bulk content. The extent of released nickel was small and related to the nickel content of the surface oxides, which was largely different from the bulk content. This may explain the limited toxicity found despite the high Ni bulk content of several powders. Taken together, this study suggests relatively low acute toxicity of condensates/spatter particles formed during SLM-printing using IN939, HX, 18Ni300, 316 L, and Ti6Al4V as original metal powders.

N. Matijasic, Ana Tripalo Batos, Jasna Lenicek Krleza, Marijana Rogulj, I. Pavić

Achromobacter xylosoxidans is an aerobic, Gram-negative rod with a broad intrinsic and acquired antimicrobial resistance, usually isolated in patients with cystic fibrosis (CF), immunodeficiencies, or those undergoing invasive procedures. We report a case of a previously healthy 14-year-old girl who was hospitalized in our institution due to a prolonged, progressive cough and exertional dyspnea, which started after a mild viral respiratory tract infection. To elucidate the cause of her symptoms, a bronchoscopy was finally performed, showing bilateral purulent bronchitis caused by A. xylosoxidans, isolated from bronchoalveolar lavage (BAL) sample. Since the patient had positive serological testing for coronavirus disease 2019 (COVID-19), we concluded that it was the initial viral infection, although of a mild clinical course, the one that created favorable conditions for proliferation and further inflammation caused by A. xylosoxidans.

A. Fendler, S. Shepherd, L. Au, Mary Y. Wu, R. Harvey, A. Schmitt, Z. Tippu, B. Shum et al.

Adis Puška, Anđelka Štilić

The use of contemporary information technologies is required to increase a country's competitiveness. Cloud computing represents one of the newer solutions in the IT industry, which has been rapidly evolving on a global scale in recent years. In light of this, the competitiveness of countries in the use of cloud computing is examined in this paper. A multi-criteria analysis was used to investigate this, utilizing the standard deviation and the simple additive method. The weight of the applications covered by the Eurostat survey was determined by the standard deviation, and the countries were ranked based on their use of cloud computing in their companies using a simple additive method. The findings revealed that cloud computing is most commonly used by Danish companies, while it is least common in Poland. Furthermore, the findings indicate that Bosnia and Herzegovina (BiH) is ranked eighth in terms of cloud computing use, while the Republic of Serbia is ranked twenty-eighth. This paper concluded that companies should use cloud computing as much as possible to improve competitiveness and reduce business costs while maintaining all of the necessary programmers for good business management.

Mustafa Reşat Dabak, Anna Stavdal, M. Sargin, Yeşim Uncu, Can Öner, Ekrem Orbay, Burak Ölmez, Prof. İlhami Ünlüoğlu et al.

R. Rahmanzadeh, Matthias Weigel, Po-Jui Lu, L. Melie-García, Thanh, D. Nguyen, A. Cagol, Francesco La Rosa et al.

This paper presents different approaches to the concept of authenti- city in the context of applied linguistics and foreign language teaching. For decades, this term has been associated only with language material used in the classroom (reductionist definition), but recent studies highlight its conceptual diversification and conclude that it is determined by other, mostly contextual factors, as well as participants in interaction. Therefore, in modern approaches to foreign language teaching, the emphasis is on a dynamic and integrated approach to the concept of authenticity (Newby, 2000), where genuine input and genuine participatory tasks promoted by teachers generate students’ genuine output who thus authenticate them in the process of interaction that is situationally determined. Consequently, as a result, the notion of authenticity is reconceptualized: it is no longer an absolute category but can be considered as a pragmatic phenomenon (Shomoossi & Ketabi 2007) and a construct generated in the socio-contextual continuum (Pinner 2014, 2016), so it is viewed holistically and applies to various aspects and actors in the process of foreign language learning.

T. Jukić, Andrej Starc, D. Štubljar, V. Strojnik, Lana Pavlović, A. Ihan

The aim of the paper is to analyze the association between heart function among obese patients and Type D personality to predict the potential risk for coronary heart disease (CHD). Overall, 30 obese patients were evaluated for the DS14 score. Body mass with body mass index (BMI), systolic and diastolic blood pressure, heart rate (HR), and heart rate variability (HRV) were measured before and after a 3-month period. Half of the subjects had been instructed to exercise 4-times weakly (walking 5 km/h) for an hour, the other half did not exercise. Additionally, STAX-1, SWLS, and QOLLTI-P questionnaires had been used. All participants had a normal CRP and sedimentation rate at the enrolment and after 3-month follow up. None of the psychological tests (STAX-1, SWLS and QLLTI-P) showed statistical difference in results between June and October. Participants who exercised showed lower HR compared to participants who did not exercise. Obese patients with high DS14 score showed reduced HRV as an additional risk factor for the future cardiovascular and other stress-related diseases. Type D personality was associated with an increased risk of CHD proved by the HRV measures when the individual was not exercising. Thus, individual personality in fact correlates to autonomic regulation of the heart.

Mohamed Badine El Yattioui, D. Tomić, Eldar Šaljić

Morocco has implemented various economic policies during the last decades. If the level of growth and the modernization seems relevant, the social programs were not efficient against poverty. During and now after the pandemic, an acceleration of the reforms seems to be considered by the authorities. This paper will analyze what was done and what the main challenges are for this country.

Sanja Petković, S. Petković, Ljiljana Tadić-Latinović, J. Berendika, Biljana Tubić, S. Jungić

A malignant peripheral nerve sheath tumour (MPNST) is a highly aggressive sarcoma. This disease develops in a number of people with neurofibromatosis type 1 (NF1), which is a common genetic disease. The paper presents a patient with typical manifestations of a malignant tumour of the peripheral nerve sheath, in the form of a large tumour of primary localisation in the distal part of the left thigh and left popliteal fossa and with significant dissemination into the lung parenchyma, which was accompanied by respiratory risk. The first operation of the tumour was done four years earlier, after which the patient did not come for regular check-ups. Nine cycles of chemotherapy were performed by Doxorubicin / Ifosfamide / Mesna protocol with clinical improvement and stabilisation, but without a significant impact on the dynamics of the disease and the overall survival was 14 months. It is of utmost importance to early recognise clinical presentation of the malignant form of this tumour and active supervision of a patient with a benign form by experts. In this way, it is possible to apply the optimal treatment modality in a timely manner.

S. Rogic, Ž. Gagić

Background/Aim: Therapy of diabetes mellitus type 2 includes drugs that act as inhibitors of dipeptidyl peptidase 4 (DPP-4) enzyme. Several DPP-4 inhibitors are marketed today and although they have favourable safety profile and tolerability, they show moderate activity in controlling glycaemia. The 3D quantitative structure-activity relationship (3D-QSAR) methodology was employed in order to find pharmacophore responsible for good DPP-4 inhibitory activity and designed new compounds with enhanced activity. Methods: For 3D-QSAR model development, 48 compounds structurally related to sitagliptin were collected from ChEMBL database. Structures of all compounds were optimised in order to find the best 3D conformations prior to QSAR modelling. To establish correlation between structure and biological activity Partial Least Squares (PLS) regression method integrated in Pentacle software was used. Results: Parameters of internal and external validation (R2 = 0.80, Q2 = 0.64 and R2 pred = 0.610) confirmed reliability of developed QSAR model. Analysis of obtained structural descriptors enabled identification of key structural characteristics that influenced DPP-4 inhibitory activity. Based on that information, new compounds were designed, of which 35 compounds had a better predicted activity, compared to sitagliptin. Conclusion: This QSAR model can be used for DPP-4 inhibitory activity prediction of structurally related compounds and resulting pharmacophore contains information useful for optimisation and design of new DPP-4 inhibitors. Finally, authors propose designed compounds for further synthesis, in vitro and in vivo testing, as new potential DPP-4 inhibitors.

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