International interest in development of treat-to-target (T2T) in both childhood-onset systemic lupus erythematosus (cSLE) and adult-onset SLE (aSLE) is increasing. T2T could facilitate more effective and structured use of treatments, aggressively controlling disease activity, preventing organ damage, and improving health-related quality of life. The first step is the selection of an appropriate target. Remission is deemed the ultimate target, but may not be attainable by all. Low disease activity (LDA), based on the principle of “tolerable” disease activity on stable treatment, with low corticosteroid dosage, may be more appropriate for some patients. The aim of this study was to derive a consensus-based cSLE appropriate definition of LDA, building upon existing aSLE definitions to improve applicability to cSLE, whilst maintaining sufficient unity to ensure that future T2T studies including adolescents and adults together are possible. The International cSLE T2T Task Force, including 18 specialists from paediatric rheumatology/nephrology, and adult rheumatology undertook a series of Delphi surveys, exploring views on aSLE LDA targets. Two virtual consensus meetings were held, utilising a modified nominal group technique to debate, modify, and vote upon topics underpinning the cSLE LDA target and its criteria. Agreement of > 80% was considered consensus. The task force agreed that the LDA target should encompass cSLE as a whole and be based upon the aSLE Lupus Low Disease Activity State definition (LLDAS), with modifications to make it more applicable to cSLE (cLLDAS, all 100% agreement). A conceptual definition of cLLDAS was defined: ‘A state, which if sustained, is associated with a low likelihood of adverse outcome (considering disease activity, damage, and medication toxicity)’ (100% agreement). Five cLLDAS criteria were agreed, as detailed within Table 1. The final cLLDAS definition was endorsed by the Paediatric Rheumatology European Society (PReS) Executive Council and PReS cSLE Working Party Chair, on behalf of the Society. A cSLE, age-appropriate definition of cLLDAS has been generated, preserving sufficient unity with the aSLE LLDAS definition to encourage life-course research. The development and validation of targets has been a key enabler for T2T trials, therefore this initiative represents a significant step forward for cSLE. Disclosure E.M.D. Smith: None. A. Aggarwal: None. J. Ainsworth: None. E. Al-Abadi: None. T. Avcin: None. L. Bortey: None. J. Burnham: None. C. Ciurtin: None. C.M. Hedrich: None. S. Kamphuis: None. D. Levy: None. L. Lewandowski: None. N. Maxwell: None. E. Morand: None. S. Ozen: None. C. Pain: None. A. Ravelli: None. C. Saad Magalhaes: None. C. Pilkington: None. D. Schonenberg: None. C. Scott: None. K. Tullus: None. M.W. Beresford: None.

Objective. The aim of this study was to present data on the prevalence of seropositive children tested in the laboratory of the Eurofarm polyclinic in Sarajevo, from September 2020 to May 2021. Material and Methods. Peripheral blood samples were collected and anti-SARS-CoV-2 antibodies were detected using an electrochemiluminescence immunoassay. Results. In the total of 762 tested children, 187 were positive (24.5%), based on cut-off value. Of all the positive cases 42.8% were female while 57.2% were male. There were 10.1% of positive children in the first age group (0-5 years), 44.4% in the second group (6-13 years), and 45.5% in the third group (14-18 years). There was no statistically significant difference in seroprevalence between age groups and gender. The lowest seroprevalence (3.6%) was observed in October 2020 after the first pandemic wave, and the highest seroprevalence (60.3%) was observed in April 2021, corresponding to the third pandemic wave. Conclusion. The results of our study showed that the seroprevalence in children was low, especially during the first year of the pandemic. In the second year of the pandemic, there was an evident statistically significant increase in the number of seropositive children. Similar data have been shown in studies for adults.

Simple Summary The aim of the study was to determine the morphological and morphometrical features of the auditory ossicles in the red fox. Moreover, for the first time, shape analysis was performed on all the middle ear bones by geometric morphometry. The auditory ossicles play a vital role in transmitting sound waves through the middle ear. The malleus was considered to be the largest bone, with three distinctive processes. The overall shape of the incus was found to be similar to that in other mammals. The presence of a prominent muscular process was noted on the head of the stapes and the convex base which closes the window of the inner ear. Abstract The use of carnivores as experimental models in auditory biology has led to a significant improvement regarding our understanding of the structure and function of the ear. Considering that data regarding the anatomy of the middle ear in the red fox are rare, this study aimed to describe the morphological and morphometrical features of the auditory ossicles in the red fox, as well as to provide their shape characteristics by geometric analysis. Nine adult red foxes were used in the study. The malleus, incus and stapes were extracted from the middle ear, prepared, photographed and measured using the software. For the geometric analysis, 19 landmarks were used. Following Principal Component Analysis (PCA), PC1 was found to explain approximately half of all variance (incus: 49.97%; malleus: 49.93%; stapes: 58.49%). The study demonstrated the similar anatomical organization of the auditory ossicles in line with important morphometric and basic geometric data, which can contribute to this field and add a useful perspective to the literature.

Background: A higher frequency of premature ventricular complexes is associated with a higher risk of premature ventricular complex-induced cardiomyopathy. Although there are several studies on the systolic functions of the left ventricle in this patient group, it is clearly not known how the diastolic functions of the left ventricle are affected. This study examined the effect of premature ventricular complex on left ventricle diastolic functions using diastolic strain rate. Methods: The trial included 57 patients with frequent premature ventricular complexes and 54 healthy volunteers. The patient was evaluated using echocardiography in its entirety. The vendor-independent software system determined systolic and diastolic strain parameters via 2-dimensional speckle tracking analysis. Using the auto strain 3P semi-automated endocardial boundary tracking instrument, the global longitudinal strain was measured from the apical 4-chamber, 2-chamber, and long axis. The diastolic strain rate was determined by averaging the strain rates of 17 cardiac segments at 2 distinct periods of diastole. Results: In the patient group, early diastolic strain rate was significantly lower than that in the control group (1.62 ± 0.58 vs. 1.25 ± 0.38, P < .001). There were found to be significant negative connections between PVC's electrocardiographic QRS wave length and early diastolic strain rate and coupling interval and early diastolic strain rate. Significant positive associations between coupling interval and early diastolic strain rate were discovered (P < .001 and P < .001, respectively). Conclusions: Patients with premature ventricular complex exhibited a lower early diastolic strain rate than healthy individuals. The early diastolic strain rate can be used to predict left ventricle diastolic dysfunction, and persons with premature ventricular complex may have a higher risk of left ventricle diastolic dysfunction than the general population.

Objective. The aim of this study was to investigate students’ knowledge, attitudes and hesitancy regarding COVID-19 vaccination. Methods. A cross-sectional questionnaire-based survey was conducted among a total of 1282 medical students and 509 non-medical students at four public universities in Bosnia and Herzegovina: Tuzla, Sarajevo, Banja Luka, and Mostar. Results. A significantly higher rate of vaccination was observed in the group of medical students as well as a higher level of knowledge about vaccination in general and vaccines against the COVID-19 disease. Students who received the COVID-19 vaccine had a higher level of knowledge about vaccination in general and COVID-19 vaccines in particular compared to the non-vaccinated students in the medical and non-medical groups, respectively. Furthermore, vaccinated students, regardless of the course they are taking, showed generally stronger positive attitudes compared to non-vaccinated students, regarding the safety and effectiveness of the COVID-19 vaccine. Both groups of students believe that the rapid development of the vaccine is contributing to refusal or hesitancy to receive a vaccine against COVID-19. Social media/networks were the main sources of information about the COVID-19 vaccine. We did not find any contribution of social media to the reduced level of COVID-19 vaccine coverage. Conclusion. Education of students about the benefits of the COVID-19 vaccine will lead to its better acceptance as well as the development of more positive attitudes towards vaccination in general, especially having in mind that students are the future population of parents, who will make decisions about vaccinating their children.

Background Since its outbreak in early 2020, the COVID-19 pandemic has diverted resources from non-urgent and elective procedures, leading to diagnosis and treatment delays, with an increased number of neoplasms at advanced stages worldwide. The aims of this study were to quantify the reduction in surgical activity for indeterminate thyroid nodules during the COVID-19 pandemic; and to evaluate whether delays in surgery led to an increased occurrence of aggressive tumours. Methods In this retrospective, international, cross-sectional study, centres were invited to participate in June 22, 2022; each centre joining the study was asked to provide data from medical records on all surgical thyroidectomies consecutively performed from Jan 1, 2019, to Dec 31, 2021. Patients with indeterminate thyroid nodules were divided into three groups according to when they underwent surgery: from Jan 1, 2019, to Feb 29, 2020 (global prepandemic phase), from March 1, 2020, to May 31, 2021 (pandemic escalation phase), and from June 1 to Dec 31, 2021 (pandemic decrease phase). The main outcomes were, for each phase, the number of surgeries for indeterminate thyroid nodules, and in patients with a postoperative diagnosis of thyroid cancers, the occurrence of tumours larger than 10 mm, extrathyroidal extension, lymph node metastases, vascular invasion, distant metastases, and tumours at high risk of structural disease recurrence. Univariate analysis was used to compare the probability of aggressive thyroid features between the first and third study phases. The study was registered on ClinicalTrials.gov, NCT05178186. Findings Data from 157 centres (n=49 countries) on 87 467 patients who underwent surgery for benign and malignant thyroid disease were collected, of whom 22 974 patients (18 052 [78·6%] female patients and 4922 [21·4%] male patients) received surgery for indeterminate thyroid nodules. We observed a significant reduction in surgery for indeterminate thyroid nodules during the pandemic escalation phase (median monthly surgeries per centre, 1·4 [IQR 0·6–3·4]) compared with the prepandemic phase (2·0 [0·9–3·7]; p<0·0001) and pandemic decrease phase (2·3 [1·0–5·0]; p<0·0001). Compared with the prepandemic phase, in the pandemic decrease phase we observed an increased occurrence of thyroid tumours larger than 10 mm (2554 [69·0%] of 3704 vs 1515 [71·5%] of 2119; OR 1·1 [95% CI 1·0–1·3]; p=0·042), lymph node metastases (343 [9·3%] vs 264 [12·5%]; OR 1·4 [1·2–1·7]; p=0·0001), and tumours at high risk of structural disease recurrence (203 [5·7%] of 3584 vs 155 [7·7%] of 2006; OR 1·4 [1·1–1·7]; p=0·0039). Interpretation Our study suggests that the reduction in surgical activity for indeterminate thyroid nodules during the COVID-19 pandemic period could have led to an increased occurrence of aggressive thyroid tumours. However, other compelling hypotheses, including increased selection of patients with aggressive malignancies during this period, should be considered. We suggest that surgery for indeterminate thyroid nodules should no longer be postponed even in future instances of pandemic escalation. Funding None.

Objectives. The main objective of this paper was to examine the perceptions of family physicians on the use of primary health care in Bosnia and Herzegovina during the COVID-19 pandemic. Materials and Methods. A cross-sectional study was conducted using a short online questionnaire that was sent to primary care physicians in Bosnia and Herzegovina from April 20th, 2022, to May 20th, 2022. Results. The research sample consisted of 231 doctors of primary health care from Bosnia and Herzegovina, with an average age of 45 years and 85% women. About 70% of participants reported having COVID-19 at least once from March 2020 to March 2022. Participants had an average of 1,986 registered patients and approximately 50 encounters per day. The study revealed a high degree of reliability between test-retest measurements, with a single measure Intraclass correlation coefficient of 0.801, and internal consistency determined using Cronbach’s alpha of 0.89. Participants reported that the following health services were most affected during the COVID-19 pandemic: care for patients with chronic diseases, home visits, navigating the health system with patients making appointments with specialists, cancer screening, and preventive health services. The study also found statistically significant perceived differences in the use of these health services based on age, gender, postgraduate education in family medicine, participation in COVID-19 clinics, and personal history of Covid-19. Conclusion. There were significant disturbances to the use of primary health care during the COVID-19 pandemic. Future research could investigate patient outcomes compared to family physician perceptions.

As one of the important enabling techniques for 6G, wireless caching network (WCN) attracts significant attentions. In this paper, we jointly apply unmanned aerial vehicle (UAV), millimeter wave (mmWave) multiple input multiple output (MIMO) and non-orthogonal multiple access (NOMA) in WCN. Our aim is to minimize the user delay, which is decomposed into three sub-problems, i.e., UAV deployment, hybrid beamforming and power allocation. Firstly, to improve the user rate, we apply K-means to reduce the distance between UAVs and users and propose a user pairing method to maintain the channel gain gap in each pair. Then, for increasing UAV hit probability, particle swarm optimization (PSO) and zero forcing are used for analog beamforming and digital beamforming, respectively. Finally, to further improve the user data rate, the genetic algorithm (GA) is applied to calculate the optimal NOMA power allocation factors. Simulation results confirm that the proposed schemes can achieve lower user delay compared with baseline schemes.

Implicit certificates are gaining ever more prominence in constrained embedded devices, in both the internet of things (IoT) and automotive domains. They present a resource-efficient security solution against common threat concerns. The computational requirements are not the main issue anymore, with the focus now shifting to determining a good balance between the provided security level and the derived threat model. A security aspect that often gets overlooked is the establishment of secure communication sessions, as most design solutions are based only on the use of static key derivation, and therefore lack the perfect forward secrecy. This leaves the transmitted data open for potential future exposures as keys are tied to the certificates rather than the communication sessions. We aim to close this gap and present a design that utilizes the Station to Station (STS) protocol with implicit certificates. In addition, we propose potential protocol optimization implementation steps and run a comprehensive study on the performance and security level between the proposed design and the state-of-the-art key derivation protocols. In our comparative study, we show that we are able to mitigate many session-related security vulnerabilities that would otherwise remain open with only a slight computational increase of 20% compared to a static elliptic curve digital signature algorithm (ECDSA) key derivation.

The 5G ecosystem is comprised of the cellular 5G System, as well as a managed and orchestrated infrastructure providing virtualized network and service functions. The automotive industry with its stringent requirements for connected vehicles is a promising and yet challenging consumer of such 5G ecosystem. Deployment of service instances at distributed cloud resources of cellular network infrastructure edges enables localized low-latency access to these services from moving vehicles but comes along with challenges, such as the need for fast reconfiguration of the distributed deployment according to mobility pattern and associated service and resource demand. In this paper, we investigate a solution for the collaborative orchestration of services for Connected, Cooperative and Automated Mobility (CCAM) within such 5G ecosystem. A key objective is the service continuity for a highly dynamic automotive scenario, achieved by the associated management and orchestration of these services in distributed edge clouds. The proposed solution leverages a multi-tier orchestration system as well as localized management and protocol operations for collaborative edge resources. By means of both analytical and experimental evaluations, the paper draws conclusions on the gain in accelerating orchestration decisions and enforcements, while balancing associated protocol and computational load over the highly distributed and multi-layered orchestration system.