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Vincent Charpentier, Giada Landi, Eleni Giannopoulou, Juan Brenes, Miguel Camelo, J. Marquez-Barja, Nina Slamnik-Kriještorac

The transition from 5G to 6G networks will catalyze the development of advanced 6G Applications (6G Apps) with enhanced network programmability and intelligence, providing vertical industries and Communication Service Providers (CSPs) with new opportunities to optimize their operations. This article explores the future of the 6G Apps tailored to verticals in the 6G era, highlighting their role as middleware that abstracts network complexities and exposes Application Programming Interfaces (APIs) to enable dynamic interaction and real-time adaptation. Key enablers such as network exposure, Artificial Intelligence (AI), and edge computing are studied in the context of optimizing operations across verticals, and improving Quality of Service (QoS) and fostering innovation. A case study on teleoperated vehicles exemplifies the real-world applicability of these technological enablers for 6G Apps. Furthermore, this article offers insights and explores new research opportunities for 6G Apps tailored to verticals to evolve in the 6G era while addressing key challenges in deploying these applications in real-world commercial networks as a service.

Ivan Keser, S. Štraus, Denis Imamovic, Mirko Mihalj

Background In low- and middle-income countries, particularly during the COVID-19 pandemic, the availability of epidural analgesia for labor has been limited due to a shortage of anesthesiologists. As an alternative, single-shot spinal analgesia can offer effective pain relief during childbirth. Objective The objective of the study is to evaluate patient satisfaction with single-shot spinal analgesia provided during labor. Methods This descriptive cross-sectional study was conducted at the General Hospital Sarajevo over a two-year period. Fifty parturients received single-shot spinal analgesia during the active phase of labor (cervical dilatation ≥ 5 cm). The analgesic mixture included 0.5% levobupivacaine (0.5 mL), fentanyl (25 mcg), and 0.9% NaCl (1 mL). Pain intensity was assessed using a Visual Analog Scale (VAS) before the procedure, 10 minutes afterward, one hour after administration, and during delivery. Data were collected using a structured questionnaire. Results The average duration of labor pain prior to the procedure was four hours. Mean VAS scores were 9 before the procedure, 3 after 10 minutes, 1 after one hour, and 4 during delivery. Spinal analgesia lasted approximately 110 minutes. During this period, 66% of parturients delivered, while in 34%, the effect of analgesia ended before delivery. All patients expressed satisfaction with the analgesia received. Conclusion Single-shot spinal analgesia provided effective pain relief and high patient satisfaction, even among those who did not deliver during the period of analgesic effect. It offered parturients sufficient time to rest and actively participate in the final stage of labor.

S. Kobal, Q. Ciampi, R. Arbucci, A. Zagatina, E. Kalinina, R. Padang, Garvan C. Kane, H. Villarraga et al.

S.T.C. Shepherd, C. Kelly-Morland, S. Drage, A. F. Brady, R. Macwana, L. Pickering, J. Larkin, P. Hill et al.

Background Belzutifan, a selective hypoxia-inducible factor-2α inhibitor, is approved for von Hippel–Lindau (VHL) disease-associated tumours and is Food and Drug Administration-approved for the management of advanced sporadic clear-cell renal-cell carcinoma. While belzutifan has demonstrated efficacy across VHL-related lesions, real-world safety data remain limited. Patients and methods We report a fatal intracranial haemorrhage occurring within 72 h of belzutifan initiation in a patient with VHL-associated central nervous system haemangioblastomas (CNS-HBs). Results This represents the third post-marketing case of early haemorrhage involving CNS or spinal haemangioblastomas, following previously reported spinal and cerebellar bleeds. Although CNS-HBs are highly vascular, spontaneous haemorrhage is exceedingly rare. The clustering of haemorrhagic events in these cases, within days of treatment initiation, suggests a rare but potentially serious adverse event not currently listed on regulatory labels. Conclusions This case highlights the importance of pharmacovigilance as belzutifan use expands into broader real-world populations, particularly in rare disease settings where trial cohorts are small and long-term safety data are limited.

N. Sabanovic-Bajramovic, I. Melezovic, A. Dzubur, A. Iglica, E. Begic, A. Dokic-Vejzovic, A. Begic

Iron deficiency (ID) is a major problem in heart failure (HF) patients. Iron deficiency is often pressent in patients with rheumatoid arthritis (RA), can be a cause of fatigue and linked with reduced functional capacity. The relationship between ID and right ventricular (RV) systolic function in patients with RA is still not well understood. The aim of this study was to analyze the relationship between ID and RV systolic function. A forty six female patients with seropositive RA were included in our study. Primary goal was to determine association between iron deficiency and echocardiography parameters such as Tricuspid annular plane systolic excursion TAPSE, RV fractional area change (RV FAC), TDI-Derived tricuspid lateral annular systolic velocity (RV TDI S’), Pulmonary artery systolic pressure (PASP); RV free wall global longitudinal strain (RVfwGLS), RV global longitudinal strain (RV GLS) and Right ventriculoarterial coupling (RVAC). The RVAC was determined with the RVfwGLS/PASP ratio. RA was diagnosed according to the ACR/EULAR 2010 classification criteria, without other significant comorbidity. ID was defined as ferritin levels lower than 100 ng/mL and iron levels lower than 10 µmol/L. The mean age of stady population was 57±8 years. Iron deficiency was found in 48% of analysed RA patients. On transthoracic echocardiography the median TAPSE was 18.3 mm, the mean FAC % 38.4±.6.3, the mean RV GLS %-17.2±7.5, the mean RVfwGLS % -20.6±3.8, the mean RV TDI S’ was 10.6±3.9 cm/s, the mean PASP was 29,2±8.7mmHg, the mean RVAC was 0.76. There was no notable difference in demographics or in TAPSE, RV FAC, RV TDI S’, and PASP between patients with iron deficiency and those without. The RVfwGLS (-16.7% vs -21.2%, p = 0.005) was lower in patients with ID. RV GLS (-14.3% vs -18.6%, p=0.005) was lower in patients with ID. Additionally, RVAC (0.65 vs 0.91, p=0.005) was lower in patients with ID. A significant correlation exists between iron deficiency and subclinical RV dysfunction, defined as reduced RV GLS, RVfwGLS and RVAC prior to the decline of parameters commonly used on echocardiography to measure right ventricle systolic function (TAPSE, RV FAC, PASP and RV TDI S'). Screening for iron deficiency in RA patients facilitates early detection and treatment of iron deficiency which may prevent RV dysfunction.

E. K. Farhat, Ines Banjari, Amina Džidić-Krivić, Malik Ejubović, E. Sher

The exact cause of autism spectrum disorder (ASD) is yet unknown, although possible causes include early childhood, foetal development, gestation, delivery mode, genetics, and environmental variables. Approximately 1% of children worldwide have ASD, and this percentage is rising. The immunological, endocrine, gut microbiota and brain-gut axis quality influence the intensity of ASD symptoms. Deficits in the composition and diversity of gut microbiota are common in children with ASD, accounting for 9-90% of these illnesses, including elevated inflammatory cytokines, inflammation, leaky gut syndrome, and pathological microflora growth. Dysbiosis can be made worse by eating issues that are prevalent in ASD. B vitamins, such as cobalamin and folate, which are essential methyl donors for DNA epigenetic changes, are usually produced by a healthy gut microbiota. 50% of people with ASD have a vitamin B deficit. This work summarises research on the impact of gut microbiota on DNA methylation and B vitamin synthesis in ASD, as well as etiological variables connected to dysbiosis. Probiotics, postbiotics, and vitamin B therapies in kids with ASD should be investigated in future studies.

K. Jerltorp, J. Castelein, O. Bohm, S. D. Nissen, A. Saljic, M. N. Noerregaard, L. Friderichsen, B. S. Larsen et al.

Abstract Background Extensive catheter ablation beyond pulmonary vein isolation may acutely increase atrial tissue stiffness, however, this may differ between energy sources used. Objectives This study aimed to compare acute effects of radiofrequency ablation (RFA) and pulsed field ablation (PFA) on atrial tissue stiffness in a porcine model using multifrequency magnetic resonance elastography (MMRE). Methods In 17 pigs (∼50 kg and ∼16 weeks old) an intercaval line was ablated using only focal RFA (25 W, 30 sec, n=9), only focal monopolar biphasic PFA (CENTAURI PFA generator, 25 A, 10 pulse trains, n=5), or half of the ablation line with PFA and the other half with RFA (n=3) (Figure 1,A). Post-ablation, in vitro MMRE data were acquired with a tabletop MRE scanner (ttMRE) (n=8) (Figure 1,B). In vivo, a novel MMRE protocol utilizing electrocardiography-triggered spin-echo, echo-planar-imaging was established (n=11) (Figure 1,C). Shear wave speed (SWS) was reconstructed as a surrogate for tissue stiffness. Results In vitro ttMRE measurements revealed significantly higher SWS for the RFA ablation zone compared to both the PFA ablation zone (p=0.008) and PFA border zone (p=0.003). Consistently, a novel in vivo MMRE protocol showed 1.37-fold higher SWS of the RFA ablation zone than its border zone (p=0.016) and 1.16-fold higher SWS than the PFA ablation zone (p=0.033). Absolute in vivo SWS differences between ablation zones and border zones were significantly higher for RFA compared to PFA (p=0.019). Conclusions RFA produces stiffer acute atrial lesions compared to PFA in pigs. A novel MMRE scanning protocol allows RFA and PFA lesion evaluation in vivo with the potential to support the refinement of future catheter approaches by optimizing mechanical properties of ablation lesions and minimizing atrial stiffness.

J. Norup Hertel, S. Dalgas Nissen, L. Lindberg, M. Schneider, A. Niskala, J. L Isaksen, K. Jerltorp, C. Ye et al.

Abstract Background Endocardial atrial fibrillation (AF) ablations using thermal energy sources modulate ganglionated plexi (GP). Contrarily, endocardial pulsed field ablation (PFA) has minimal effect on GP located within the epicardial fat-pads. Purpose To determine structural and antiarrhythmic effects of direct epicardial PFA-delivery to atrial GP-sites. Methods Group-1: Epicardial PFA-delivery to GP sites (n=6 pigs). Group-2: Sham-operated (n=2 pigs). Thoracotomy was performed and five epicardial GP-sites were identified and targeted by saline-irrigated bipolar PFA (1,000V, 100μs, 120-pulses, ECG-synchronised). Local atrial electrogram (EGM) amplitude, atrial effective refractory period (aERP) and AF (inducibility and duration) were investigated. Histology was performed on samples from treatment-adjacent structures. Results In Group-1, 120 PFA-pulses were successfully delivered epicardially to each GP-site. Local EGM-amplitudes did not change after PFA-delivery. GPs showed lower intensity of S100-protein expression within the cytoplasm and membrane with preservation of adjacent atrial myocardium. The aERP at the higher and lower lateral right atrium increased from 123±34ms to 173±47ms (p=0.0358) and from 122±32ms to 221±16ms (p=0.0063) after PFA-treatment, respectively. Total AF-inducibility decreased from 100% to 33%, inducible AF-duration decreased from 4.4±0.6min (including 2 cardioversions) at baseline to 1.3±2.1min (including 1 cardioversion) after PFA-delivery (decrease: -3.2±2min, p=0.007). In one pig, the feasibility of thoracoscopic epicardial PFA delivery at all anatomical GP-sites was shown. Conclusion Epicardial PFA-delivery to anatomical GP-sites is feasible in open-chest or thoracoscopic approach, and acutely decreases GP S100-protein intensity, prolongs aERP and reduces AF-inducibility and duration.

Nedim Tuno, Goran Marinković, Admir Mulahusić, Jusuf Topoljak, D. Kogoj, Simona Savšek

Sergii S. Kryvenko, Vladimir Lukin, Boban P. Bondzulic, Nenad Stojanović

The object of the study is the process of compressing noisy images in a lossy manner by better portable graphics (BPG) encoder. The subject of the study is the method for adaptive selection of the coder parameter Q depending on noise intensity and image complexity. The goal of the study is to consider the basic characteristics of lossy compression of remote sensing images contaminated by additive white Gaussian noise with giving recommendations of preferable Q setting. Methods used: numerical simulation, verification for test images. Results obtained: 1) the dependencies of compression ratio on Q are monotonically increasing functions; 2) their characteristics are strongly dependent on noise intensity and image complexity; 3) dependencies of logarithm of CR on Q contain information on possible existence and position of optimal operation point for compressed noisy images; 4) compression ratios for large Q contain information on image complexity with low sensitivity to noise presence and intensity; 5) it is possible to get useful information from dependences of compression ratio on Q. Conclusions: the results of this research allow: 1) estimating image complexity; 2) adapting Q to noise intensity and image complexity. 

Kenan Galijašević, Adnan Mujezinović, Amir Denjalić

Introduction: Carcinomas of the right and left sides of the colon are considered different types of cancer due to their different carcinogenesis, epidemiology, pathology and prognosis. Although several studies have described the prevalence and incidence of colorectal carcinoma (CRC) in the different colonic segments, more epidemiologic data are still needed to better understand the implications and relationship to sociodemographic and clinical variables. The aim of this study is to determine the anatomic location and histologic grade of CRC, to investigate the differences in patient gender and age, and to determine the correlation of gender and age with the anatomic location and histologic grading of CRC. Methods: A retrospective study was conducted covering the period from January 2013 to December 2022. Demographic data (gender and age), histological type and anatomical location of the tumor were observed. The study included all patients in the observed period with a diagnosis of colorectal cancer (CRC) at different anatomical locations and with different grades of histological staging. All patients had adenocarcinoma. Patients were divided into four age groups based on their gender (20-40 years, 41-55 years, 56-65 years and over 65 years old). Tumors of the colon ascending to the splenic flexure are defined as tumors of the right side, and distal to the splenic flexure as tumors of the left side of the colon. Results: A total of 183 patients were included in the study. Patients were between 38 and 82 years old, with a mean age of 64.3 ± 8.9 years. No statistically significant difference was found in the proportion of anatomical localization of CRC (p > 0.05). The most common anatomical location of CRC over the 10-year period was found to be the rectum 42.1% and the ascending colon 14.2% and transverse colon 13.1%, with no statistically significant difference in cancer incidence between the right and left sides of the colon. Histologic grade II was predominant in 57.4% of patients. A moderate negative correlation was found between age and histologic grade of CRC (r = −0.067), with no statistically significant difference (p > 0.05). Conclusion: No statistically significant difference was found in the anatomical localization of CRC between the right and left side of the colon. Histologic grade II CRC was the most prevalent. A moderate negative correlation was found between age and histologic grade of CRC.

Andi Alijagic, E. Särndahl, O. Kotlyar, Patrik Karlsson, D. Duberg, N. Scherbak, A. Pinsino, Magnus Engwall et al.

Per- and polyfluoroalkyl substances and nanoplastics frequently co-occur in environmental matrices, yet the effects of co-exposure on cellular responses upon ingestion are poorly understood. Here, we exposed human intestinal Caco-2 cells to perfluorooctanesulfonic acid, nanoplastics, and their combination. Cell painting-based phenomics was used to map phenotypic alterations across subcellular structures, and untargeted metabolomics using ultra-high-performance liquid chromatography coupled to quadrupole time-of-flight mass spectrometry was employed to assess metabolic changes. Results show that perfluorooctanesulfonic acid predominantly affected the actin cytoskeleton, Golgi apparatus, and plasma membrane, while nanoplastics primarily targeted mitochondria. Combined exposure disrupted the endoplasmic reticulum, RNA, and mitochondria. Perfluorooctanesulfonic acid reduced levels of carnitines, free fatty acids, nucleotides, and sugars, whereas nanoplastics inhibited ceramides, triglycerides, sphingomyelins, and additional free fatty acids. Combined exposure produced a metabolic profile resembling that of nanoplastics, with specific differences attributed to perfluorooctanesulfonic acid. Overall, nanoplastics appear as the main drivers of the co-exposure effects.

Jovana Dervovic, Š. Goletić, Alma Šeho-Alíć, S. Prašović, T. Goletić, A. Alić

The etiology of transmissible viral proventriculitis (TVP) of broiler chickens has been discussed since its initial recognition 40 years ago. Regardless of its low direct impact on mortality rate, it leads to high economic losses in the broiler industry through reduction of food conversion, weakening of birds, and their increased susceptibility to pathogens. The aim of the present study was to examine the potential presence of TVP on the broiler chicken farms in Bosnia and Herzegovina, to characterize microscopic lesions, and to investigate the viruses implicated in etiology of TVP by PCR-based methods. In total, 143 diseased broiler chickens from 16 farms in Bosnia and Herzegovina were euthanized and subjected to necropsy and subsequent histopathology of proventriculi. A representative number of proventriculi samples (n = 50) that exhibited histopathologic changes were processed for molecular detection of chicken proventricular necrosis virus (CPNV), girovirus (GyV3), chicken anemia virus (CAV), and infectious bursal disease virus (IBDV) by PCR-based methods. In addition, samples of bursa of Fabricius (n = 39) and spleen (n = 50) were tested for IBDV. Histopathology revealed changes consistent with TVP in 39.8% (57/143) and LP (lymphocytic proventriculitis) in 2.1% (3/143) of samples. All 50 proventricular samples showed positivity to CPNV with Ct values ranging between 18 and 26. GyV3 was detected in eight samples (16%), with Ct values ranging from 11.1 to 27.5. The presence of CAV was more prominent (38%), with 19 positive broiler chickens (Ct ranging from 9.6 to 35.6). Pooled samples of spleen, bursa, and proventriculi from three farms were positive for IBDV. The obtained results represent the first documented data on TVP and the first record of CPNV and GyV3 presence in broiler farms from Bosnia and Herzegovina.

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