This study investigates the use of deep learning algorithms to predict the discharge coefficient (Cd) of contaminated multi-hole orifice flow meters with circular opening. Datasets (MHO1 and MHO2) were obtained from computational fluid dynamic simulations for two circular multi-hole orifice flow meters of different geometries. To evaluate the performance and generalization capabilities of different models, three distinct scenarios, each involving different dataset configurations and normalization techniques were designed. For each scenario, three deep learning models (feedforward neural networks, convolutional neural network, and recurrent neural network) were implemented and evaluated based on their performance metrics, including mean squared error (MSE), root mean squared error (RMSE), mean absolute error (MAE), and the coefficient of determination (R2). For all three scenarios eight models for each neural network model were developed (FFNN – four models, CNN – two models, RNN – two models). The same structure of models was used across all scenarios to ensure consistency in the evaluation process. Key input parameters include geometrical and flow variables such as β – parameter, contamination thickness, radial distance, Reynolds number, and orifice diameters. Results demonstrate the effectiveness of deep learning in accurately predicting discharge coefficient for different contamination conditions and different geometries. This study showed that deep learning models can be used for prediction of discharge coefficients for multi-hole orifice flow meters of similar geometry, based on data obtained from one orifice flow meter for different contamination parameters.

Background: Three-dimensional printing is used in veterinary medicine to produce precise physical models for education, research, and training. As simulation-based approaches in veterinary education continually improve, we are exploring the applicability of three dimensional (3D) printing technology for this purpose. Aim: The aim of this study was to evaluate the level of student satisfaction, motivation, and confidence with the introduction of 3D-printed models in veterinary clinical training. Methods: A total of 57 students from the University of Sarajevo–Veterinary Faculty were included in the study. The groups were created according to the previous clinical training: third-year students with dominant observational and little active participation, fourth-year students with modest active participation, and fifth-year students with high prominent active participation in the clinical work. The students attended the theoretical review and practical presentation prior to their work on 3D printing models. Upon completion of the activity, students were given a survey that included questions divided into four categories: general satisfaction, comparison with traditional teaching methods, interactivity and practical application, and technical characteristics. Results: Students exhibited a positive attitude toward the use of the three dimensional printing (3DP) models as clinical simulators. This innovative approach could reduce stress when transitioning to work with live animals while enhancing interest in clinical work. Conclusion: The significant benefits of the 3DP include enhanced durability, low production costs, and a significant reduction in the number of cadavers needed for educational purposes.

The aim of this study was to examine the gender-specific criterion validity of the Physical Activity Questionnaire for Children (PAQ-C) in a sample of urban Croatian early school-age children. The participants were 80 children (aged 9-11 years; 36 girls, 44 boys) from southern Croatia. The PAQ-C was used to indirectly measure physical activity (PA), whereas the GENEActiv accelerometers were used to obtain data on PA directly. Spearman’s correlations between variables, and forward multiple regressions were calculated separately for boys and girls. The differences in the studied variables between genders were established via a t-test for independent samples. Boys reported higher PAQ-C scores (t test = 3.6, p<0.05), had more vigorous PA (t test =3.87, p<0.05), and performed more steps than girls did (t test =3.44, p<0.05). The correlations between the PAQ-C and accelerometer-derived data were similar in magnitude across genders. Vigorous PA was determinant of the PAQ-C in boys (Beta =0.44, p<0.05), and moderate PA was found to be a determinant of the PAQ-C in girls (Beta =0.51, p<0.05). While the criterion validity of the PAQ-C is similar for both boys and girls, by acknowledging and addressing potential gender differences in activity patterns associated with questionnaire-based scores, we can develop more effective strategies to encourage PA in children.

Summary Background Deaths from suicide are a tragic yet preventable cause of mortality. Quantifying the burden of suicide to understand its geographical distribution, temporal trends, and variation by age and sex is an essential step in suicide prevention. We aimed to present a comprehensive set of global, regional, and national estimates of suicide burden. Methods We produced estimates of the number of deaths and age-standardised mortality rates of suicide globally, regionally, and for 204 countries and territories from 1990 to 2021, and disaggregated these results by age and sex. The Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2021 estimates of deaths attributable to suicide were broken down into two comprehensive categories: those by firearms and those by other specified means. For this analysis, we also produced estimates of mean age at the time of death from suicide, incidence of suicide attempts compared with deaths, and age-standardised rates of suicide by firearm. We acquired data from vital registration, verbal autopsy, and mortality surveillance that included 23 782 study-location-years of data from GBD 2021. Point estimates were calculated from the average of 1000 randomly selected possible values of deaths from suicide by age, sex, and geographical location. 95% uncertainty intervals (UIs) were derived from the 2·5th and 97·5th percentiles from a 1000-draw distribution. Findings Globally, 746 000 deaths (95% UI 692 000–800 000) from suicide occurred in 2021, including 519 000 deaths (485 000–556 000) among males and 227 000 (200 000–255 000) among females. The age-standardised mortality rate has declined over time, from 14·9 deaths (12·8–15·7) per 100 000 population in 1990 to 9·0 (8·3–9·6) per 100 000 in 2021. Regionally, mortality rates due to suicide were highest in eastern Europe (19·2 [17·5–20·8] per 100 000), southern sub-Saharan Africa (16·1 [14·0–18·3] per 100 000), and central sub-Saharan Africa (14·4 [11·0–19·1] per 100 000). The mean age at which individuals died from suicide progressively increased during the study period. For males, the mean age at death by suicide in 1990 was 43·0 years (38·0–45·8), increasing to 47·0 years (43·5–50·6) in 2021. For females, it was 41·9 years (30·9–46·7) in 1990 and 46·9 years (41·2–52·8) in 2021. The incidence of suicide attempts requiring medical care was consistently higher at the regional level for females than for males. The number of deaths by suicide using firearms was higher for males than for females, and substantially varied by country and region. The countries with the highest age-standardised rate of suicides attributable to firearms in 2021 were the USA, Uruguay, and Venezuela. Interpretation Deaths from suicide remain variable by age and sex and across geographical locations, although population mortality rates have continued to improve globally since the 1990s. This study presents, for the first time in GBD, a quantification of the mean age at the time of suicide death, alongside comprehensive estimates of the burden of suicide throughout the world. These analyses will help guide future approaches to reduce suicide mortality that consider a public health framework for prevention. Funding Bill & Melinda Gates Foundation.

Background: There are limited therapy options in case of failed reperfusion after stent-retriever and/or aspiration based endovascular treatment (EVT) for acute ischemic stroke. Despite the absence of data supporting its use, rescue angioplasty (RA; with or without stent implantation) is often utilized in such cases. Studies are limited to large vessel occlusions, while the outcomes and complications after RA in medium/distal vessel occlusions (MDVOs) have not been reported. This study aims to report the outcomes of RA in MDVO stroke patients. Methods: We performed a retrospective sub-analysis of the “Blood pressure and Antiplatelet medication management after reScue angioplasty after failed Endovascular treatment in Large and distal vessel occlusions with probable IntraCranial Atherosclerotic Disease” (BASEL ICAD) registry. All MDVO stroke patients were included in the analysis. Results: Out of 718 patients, 92 (12.8%) presented with an MDVO. Sixty-one patients (65.9%) presented with an occlusion of the M2 segment of the middle cerebral artery. Rescue stenting (RS) was performed in 83 patients (90.2%) and balloon angioplasty alone was performed in 9 patients (9.8%). Successful reperfusion (modified thrombolysis in cerebral infarction (mTICI) score ≥ 2b) before RA was achieved in 34 patients (36.9%) and after RA in 76 (82.6%) patients. Symptomatic intracranial hemorrhage (sICH) occurred in 8 patients (9.1%) and post-treatment stent occlusion in 14 patients (16.7%). 90 days mortality was 24.1%. Twenty-nine patients (34.9%) achieved functional independence at 90 days (modified Rankin Scale 0 – 2). Conclusion: Rescue Angioplasty might be a viable treatment option in case of failed reperfusion after conventional EVT in selected MDVO patients. However, safety concerns remain.

Background: Intracranial stenting is increasingly performed after thrombectomy failure. Stent selection and procedural strategies are heterogenous between centers. Our aim is to evaluate the clinical and radiological impact of stent design among these patients. Methods: The RESISTANT registry is a multicenter, international, retrospective study of patients with acute ischemic stroke who underwent intracranial stenting from 2016 to 2023. This analysis compares outcomes based on stent type and evaluates the role of pre- and post-stenting angioplasty. The primary endpoint was 90-day good clinical outcome defined as modified Rankin Scale 0 to 2. Secondary outcomes included final reperfusion, and early stent patency (within 48 hours). Safety outcomes included procedural complications, symptomatic intracranial hemorrhage, and in-hospital mortality. Results: Among 859 patients in the RESISTANT registry, 176 underwent intracranial stenting with balloon-mounted stent (BMS) and 683 with self-expandable stent (SES). The Vertebrobasilar location was more frequent in patients who received BMS (46.6% vs 24.0%, p<0.001); other baseline variables were similar between groups. Angioplasty was performed more frequently before (SES: 54.0% vs BMS: 39.2%, p<0.001) and after SES (SES: 21.1% vs BMS: 9.2%, p<0.001). Successful reperfusion (mTICI 2b-3) was similar between groups (BMS: 91.2% vs SES: 89.1%) and the rate of residual intracranial stenosis was higher in SES patients (57.1% vs 35.6%, p<0.001). Reocclusion, procedural complications and symptomatic intracranial hemorrhage rates were similar between groups. At 90 days, the rate of good clinical outcome was higher among those patients treated with SES (44.7% vs 29.5%, aOR 1.74 (95%ICI 1.07-2.82)). Conclusions: Among patients who underwent rescue intracranial stenting, patients treated with self-expandable stents had a better outcome than patients treated with balloon-mounted stent at 90 days despite similar rates of symptomatic intracranial hemorrhage, successful recanalization and early reocclusion.

Background: Acute intracranial stenting for the treatment of patients with large vessel occlusion in case of failed reperfusion or severe stenosis is a growing practice. Our aim was to explore the clinical and radiological outcome in a large multicenter and international registry. Methods: The RESISTANT registry is a multicenter and international retrospective registry of patients with large vessel occlusion stroke that underwent intracranial stenting due an acute stroke from 2016 to 2023. Primary endpoints was clinical outcome at 90 days. Secondary efficacy endpoints were final reperfusion (mTICI 2b-3), and stent patency at 24 hours. Safety outcomes included procedural complications, symptomatic intracranial hemorrhage and in-hospital mortality. Results: Among 890 patients enrolled, 862 fulfilled inclusion criteria. Median age was 67.0 years (IQR 59.0-77.0), 558 (64.7%) were males and median NIHSS was 12 (IQR 7.0-19.0). Occlusion location was proximal in 758 (87.9%) patients and anterior circulation was affected in 613 (71.1%) patients (390 M1-MCA, 142 terminal ICA). The indication for intracranial stenting was failed reperfusion (mTICI 0-2a) in 456 patients (52.9%). After intracranial stenting, successful recanalization was achieved in 764 (88.6%) with a reocclusion rate during admission of 11.9% and missing controls of 17.7%. The rate of symptomatic intracranial hemorrhage was 8.1%. At 90 days, the median mRS was 3 (IQR 1-6). Successful recanalization and regular flow after stenting were predictors of functional outcome at 90 days. No variables were independently associated with early reocclusion or symptomatic intracranial hemorrhage. Conclusion: Acute intracranial stenting was an effective therapy for patients with failed reperfusion or severe stenosis. Successful reperfusion and regular flow after stenting predicted functional outcome. Prospective studies are warranted to confirm efficacy and safety.

OBJECTIVES Many rheumatoid arthritis (RA) patients continue to experience persistent pain even after successful management of joint inflammation. Clinical data indicate that RA patients treated with the JAK inhibitor baricitinib consistently achieve pain relief that cannot be entirely attributed to its anti-inflammatory effects. In this study, we investigated the antinociceptive properties of baricitinib using the collagen antibody-induced arthritis (CAIA) model in which mechanical hypersensitivity persists long after resolution of joint inflammation. METHODS The effects of baricitinib, etanercept (tumour necrosis factor inhibitor), and LP-922761 (adaptor protein-2 (AP2) associated kinase 1 (AAK1) inhibitor) on pain-like behaviour in CAIA mice were examined. Tissue samples from the late, low-grade inflammatory phase were examined for the effect of the treatments. Additionally, in vitro experiments using dorsal root ganglion (DRG) cells were conducted to assess baricitinib's influence on neuronal excitability and cell morphology. RESULTS Baricitinib reduced CAIA-induced joint inflammation, but its antinociceptive effects were most pronounced during the late phase when etanercept was ineffective. Administering baricitinib both early and late significantly decreased CAIA-induced bone loss, synovial innervation, and baseline STAT3 phosphorylation in ankle joints and DRGs. Unlike etanercept, baricitinib effectively reduced pain-like behaviour and synovial hyperinnervation when administered exclusively in the late phase. Additionally, baricitinib modulated glial cell morphology and neuronal excitability in vitro. Notably, it inhibited AAK1 signalling in DRGs, with AAK1 kinase activity blockade providing an antinociceptive effect in the CAIA model. CONCLUSIONS Our data suggests that baricitinib has antinociceptive effects by targeting not only immune cells but also neurons and glia cells via inhibition of 2 signalling pathways linked to chronic pain.

Continuous exploration of innovative and sustainable solutions within green chemistry is imperative to tackle challenges inherent in traditional production processes. This study examined three novel methods for obtaining polyphenolic extracts from dill seeds: nonthermal high voltage electric discharge (HVED), subcritical water extraction (SWE), and microwave-assisted extraction (MAE). SWE was conducted at temperatures ranging from 100 to 200°C under 30 bar pressure, while MAE utilized a hydroethanolic solvent at temperatures from 40 to 120°C. HVED extraction was performed at varying frequencies (40-100 Hz) and durations (5-15 min) in water. The total phenolic and flavonoid content of the extracts was quantified, and antioxidant activity was evaluated via 2,2-diphenyl-1-picrylhydrazyl (DPPH) assay. Polyphenol content and DPPH radical scavenging capacity varied across techniques, with MAE at 40°C yielding the highest values. Increasing MAE temperature caused a steep decline in total phenol and flavonoid contents and a rise in DPPH IC50 values. Conversely, SWE significantly increased phenolic recovery at temperatures between 150-200°C. HVED extraction revealed frequency as the most critical parameter for phenolic recovery. Catechin (224.88 µg/mL), epicatechin (120.62 µg/mL), epigallocatechin (107.56 µg/mL), and procyanidin B1 (116.36 µg/mL) emerged as the primary phenolics. SWE demonstrated superior suitability for individual phenolic recovery compared with the other two techniques. Multivariate data analysis reveals relationships between extraction parameters and polyphenol recovery, underscoring the potential for eco-friendly and efficient extraction processes. This study highlights the transition toward sustainable extraction methods in modern industrial processing. PRACTICAL APPLICATION: This study provides insights into innovative extraction techniques for obtaining polyphenols from dill seeds, which could be applied in the food, cosmetic, and pharmaceutical industries. The findings suggest that these eco-friendly methods can improve the efficiency of extracting antioxidants, offering manufacturers a greener and more effective approach to producing health-promoting ingredients.