Abstract Arousal dysfunction contributes to impairments seen in Alzheimer’s disease. However, the nature and degree of this dysfunction have not been studied in detail. We investigated changes in tonic and phasic arousal using simultaneous pupillometry-EEG, relating these changes to locus coeruleus integrity, a key arousal nucleus. Forty Alzheimer’s disease participants and 30 controls underwent neuropsychological testing using the Alzheimer’s Disease Assessment Scale–Cognitive Subscale (ADAS-Cog), MRI designed to show contrast in the locus coeruleus as a measure of integrity and simultaneous pupillometry-EEG during 5 min of eyes-open resting-state. Pupillometry-EEG was then also applied during an oddball task which included a passive session and sessions in which responses to target stimuli were required, to test the effect of salience. Alzheimer’s disease had lower locus coeruleus integrity (b = −0.26, P = 0.02) and lower peak alpha frequency (tonic arousal) (b = −1.09, P < 0.001). Both were related to ADAS-Cog. There was a very strong relationship between pupil size and both periodic and aperiodic EEG power. Cortical slowing in Alzheimer’s disease affected this relationship, particularly at low frequencies. During the attentionally demanding oddball task, Alzheimer’s disease participants’ behavioural performance was impaired, with reduced accuracy and slower and more variable reaction times. They also had reduced pupil responses to salient stimuli (phasic arousal) (estimate = −0.19, P < 0.001). EEG and pupil measures of pre-stimulus tonic arousal were strongly correlated and predicted behavioural responses in both groups. Arousal fluctuations at rest and in response to stimuli are abnormal in Alzheimer’s disease as measured by combined pupillometry and EEG. Salient stimuli that require a behavioural response are accompanied by a phasic increase in arousal, demonstrated by pupil dilation to oddball stimuli. This response is slower and of smaller magnitude in Alzheimer’s disease patients. Cortical slowing (reduced peak alpha frequency) is seen in Alzheimer’s disease, and this is modulated by arousal level and relates to overall cognition. Pupil-linked arousal responses and alpha EEG fluctuations are tightly coupled, but cortical slowing in Alzheimer’s disease influences this coupling. The tools used here to measure neurophysiological arousal level have potential in understanding the nature of arousal system dysfunction in Alzheimer’s disease at the group level. These tools may also be used as biomarkers at the individual level in order to target patients most likely to benefit from arousal-modulating medications.

Intravenous thrombolysis (IVT) in patients with recent ingestion of direct oral anticoagulants (DOACs) is a frequent challenge and remains controversial. The benefit of DOAC reversal before IVT is uncertain. Using target trial methodology, we analyzed data from 28 comprehensive stroke centers. Patients on DOACs were included if they met IVT criteria, had a National Institutes of Health Stroke Scale score of ≥2, and last DOAC intake within 48 hours or was undeterminable. Safety and efficacy outcomes (symptomatic intracerebral hemorrhage, any intracerebral hemorrhage, major bleeding, 90-day mortality, and good functional outcome [modified Rankin Scale score of 0–2 or return to baseline]) were compared between those receiving IVT versus no IVT and IVT with versus without reversal. In addition, a comparison was made with patients from the New Zealand stroke registry, all of whom underwent reversal with idarucizumab. We adjusted for covariates known to be associated with safety and efficacy outcomes, including age, stroke severity, intended thrombectomy, blood glucose, blood pressure, DOAC reversal, and time from last intake. Overall, 1342 patients fulfilled the target trial criteria. The median age was 80 (interquartile range, 73–86) years, median National Institutes of Health Stroke Scale score was 11, 50% were female, and 52% of patients received endovascular therapy. IVT was given in 342 of 1342 (25%) patients. Of these, 141 (41.2%) had verified DOAC intake <12 hours before admission, and 92 (26.9%) within 12 to 24 hours. Symptomatic intracerebral hemorrhage occurred in 10 of 328 (3.0%) of patients receiving IVT and 54 of 921 (5.9%) patients not receiving IVT (adjusted difference, −2.1% [95% CI, −5.3% to +1.2]). Patients receiving IVT were more likely to have good functional outcomes (adjusted difference, +14.4% [95% CI, +7.1% to +21.8%]). Comparing 289 patients with reversal (from the additional New Zealand registry) and 283 patients without reversal before IVT (from the target trial population), there was no significant difference in symptomatic intracerebral hemorrhage, major bleeding, or efficacy outcomes. This target trial confirms previous observational data regarding the safety of off-label IVT in patients with recent DOAC intake. More data and dedicated trials are needed for patients with confirmed high DOAC plasma levels and regarding the efficacy and safety of DOAC reversal before IVT.

Atmospheric climate science lacks the capacity to integrate thermodynamics with the gravitational potential of air in a classical quantum theory. To what extent can we identify Carnot’s ideal heat engine cycle in reversible isothermal and isentropic phases between dual temperatures partitioning heat flow with coupled work processes in the atmosphere? Using statistical action mechanics to describe Carnot’s cycle, the maximum rate of work possible can be integrated for the working gases as equal to variations in the absolute Gibbs energy, estimated as sustaining field quanta consistent with Carnot’s definition of heat as caloric. His treatise of 1824 even gave equations expressing work potential as a function of differences in temperature and the logarithm of the change in density and volume. Second, Carnot’s mechanical principle of cooling caused by gas dilation or warming by compression can be applied to tropospheric heat–work cycles in anticyclones and cyclones. Third, the virial theorem of Lagrange and Clausius based on least action predicts a more accurate temperature gradient with altitude near 6.5–6.9 °C per km, requiring that the Gibbs rotational quantum energies of gas molecules exchange reversibly with gravitational potential. This predicts a diminished role for the radiative transfer of energy from the atmosphere to the surface, in contrast to the Trenberth global radiative budget of ≈330 watts per square metre as downwelling radiation. The spectral absorptivity of greenhouse gas for surface radiation into the troposphere enables thermal recycling, sustaining air masses in Lagrangian action. This obviates the current paradigm of cooling with altitude by adiabatic expansion. The virial-action theorem must also control non-reversible heat–work Carnot cycles, with turbulent friction raising the surface temperature. Dissipative surface warming raises the surface pressure by heating, sustaining the weight of the atmosphere to varying altitudes according to latitude and seasonal angles of insolation. New predictions for experimental testing are now emerging from this virial-action hypothesis for climate, linking vortical energy potential with convective and turbulent exchanges of work and heat, proposed as the efficient cause setting the thermal temperature of surface materials.

The objective of the study was to assess the genetic diversity of the Tornjak shepherd dog by analyzing 10 micro- satellite loci. The dogs were divided into three main groups: Tornjaks from Bosnia and Herzegovina (TBA), Tornjaks from Croatia (THR), and a control group containing four subgroups: German Shepherd (GS), Belgian Shepherd (BS), crossbreeds of Tornjaks and other breeds (MIXT), and various other dog breeds (MIXA). The average number of genotypes (GN) and alleles (AN) was 19.2 and 8.4 (TBA), 8.2 and 5.4 (THR), 7.9 and 5.1 (BS), 4.4 and 3.6 (GS), 7.6 and 5.5 (MIXT), and 8.6 and 6.0 (MIXA), respectively. The average values of observed (HO) and expected heterozy- gosity (HE) were 0.7261 and 0.7392 (TBA); 0.7625 and 0.7139 (THR); 0.6857 and 0.6837 (BS); 0.4900 and 0.4640 (GS); 0.6786 and 0.6760 (MIXT); and 0.7067 and 0.7160 (MIXA), respectively. In the TBA population, “private” alleles were observed at all ten loci. The average overall inbreeding coefficient (F) value between the Tornjak and the control group was 0.0768. The AMOVA test revealed the highest degree of variation within the TBA group (55.43%), while no significant variations were observed in the control subgroup GS. The smallest differentiation for TBA was found with THR at 1.86% used the pairwise FST (pFST). The constructed Neighbor-Joining (NJ) dendrogram shows clear grouping of TBA and THR in comparison to the breeds of the control group. In relation to the data presented, a high level heterogeneity of has been established in the studied Tornjak population (TBA).

A systematic review with meta-analysis (SRMA) represents the pinnacle of evidence, but its validity depends on methodological rigor. This narrative review synthesizes recommendations from major reporting frameworks—Preferred Reporting Items for Systematic Reviews and Meta-Analyses 2020 (PRISMA-2020), Meta-Analysis of Observational Studies in Epidemiology (MOOSE) and Preferred Reporting Items for Overviews of Reviews (PRIOR)—into a concise checklist for peer reviewers. The checklist addresses common sources of bias that often escape editorial assessment. Initially, it outlines how reviewers should assess the rationale for an SRMA by identifying existing syntheses on the same topic and determining whether the new work provides substantive novelty or a significant update. Best practices are summarized for protocol registration, comprehensive search strategies, study selection and data extraction, risk-of-bias evaluation, and context-appropriate statistical modeling, with a specific focus on heterogeneity, small-study effects, and data transparency. Case examples highlight frequent pitfalls, such as unjustified pooling of heterogeneous designs and selective outcome reporting. Guidance is also provided for formulating balanced, actionable review comments that enhance methodological integrity without extending editorial timelines. This checklist equips editors and reviewers with a structured tool for systematic appraisal across clinical disciplines, ultimately improving the reliability, reproducibility, and clinical utility of future SRMAs.

Abstract This paper examines the relationship between populism and post-conflict power-sharing frameworks. Focusing on Bosnia and Herzegovina, it explores how populism challenges existing power-sharing arrangements, while also considering how these may foster different forms of populism. By proposing that populism in BiH should be understood as a discursive strategy that politically constructs a division shaped by different ethnic dynamics toward the dominant socio-political landscape, the paper identifies three distinct but interconnected forms of populism: inter-ethnic, intra-ethnic, and cross-ethnic.

Medical imaging plays a vital role in early disease diagnosis and monitoring. Specifically, blood microscopy offers valuable insights into blood cell morphology and the detection of hematological disorders. In recent years, deep learning-based automated classification systems have demonstrated high potential in enhancing the accuracy and efficiency of blood image analysis. However, a detailed performance analysis of specific deep learning frameworks appears to be lacking. This paper compares the performance of three popular deep learning frameworks, TensorFlow with Keras, PyTorch, and JAX, in classifying blood cell images from the publicly available BloodMNIST dataset. The study primarily focuses on inference time differences, but also classification performance for different image sizes. The results reveal variations in performance across frameworks, influenced by factors such as image resolution and framework-specific optimizations. Classification accuracy for JAX and PyTorch was comparable to current benchmarks, showcasing the efficiency of these frameworks for medical image classification.

Herein, we aimed to analyze the final diagnosis in a well-defined cohort of fever of unknown origin (FUO) cases whose erythrocyte sedimentation rate (ESR) was 100 mm/h or more during the admission. The subgroup of the FUO patients with an ESR of 100 mm/h or more during the FUO evaluation, was extracted from the study database of a previously published multicenter study (European Journal of Clinical Microbiology & Infectious Diseases. April 15, 2023;42 (4):387–98). Data for 139 patients (17.6%, 139/788 of the original cohort) who fulfilled the study inclusion criteria, were obtained from 29 centers from 11 countries. Infections, neoplasms, and noninfectious inflammatory diseases were found to be the reason of fever in [n = 74 (53.2%)], [n = 14 (10%)], and [n = 13 (9.3%)] of 139 patients, respectively. Regardless of the diseases subgroup top 6 diseases that were determined to be the reasons of FUO were tuberculosis [n = 15 (10.8%)], HIV/AIDS [n = 13 (9.3%)], urinary tract infection [n = 9 (6.5%)], infective endocarditis [n = 9 (6.5%)], lymphoma [n = 9 (6.5%)], and abscess [n = 9 (6.5%)]. The most common infectious diseases were tuberculosis (15/74, 20.2%), HIV/AIDS (13/74, 17.5%), and infective endocarditis (9/74, 12.1%), along with urinary tract infection [n = 9 (6.5%)] and abscess [n = 9 (6.5%)]. The most common noninfectious inflammatory diseases were adult onset Still disease (3/13, 23%) and giant cell arteritis, also known as temporal arteritis (3/13, 23%), and followed by polyarteritis nodosa (2/13, 15.3%). The most common neoplasm was lymphoma (9/14, 64.2%), followed by lung cancer (2/14, 14.2%). Reason of fever could not be defined in (29/139, 20.8%) patients. The invasive procedures were performed in (64/139, 46%) patients. Gender, age > 50 or not, and income level (high–middle–low) of the participating country were not associated with a significant difference in the final diagnosis category of the FUO case (P > .05). To the best of our knowledge, this is the first study evaluating the FUO in the subgroup of cases with extreme ESR elevation and infectious diseases comprised the most cause of the FUO in this particular subgroup.

This study focuses on the position of civil law research in the Web of Science (WoS) and Scopus scientific databases. Two of the most reputable university rankings, the Shanghai Ranking of World Universities (Shanghai University Rankings) and the Times Higher Education rankings, evaluate the quality of research on the law subject matter directly based on its position in the WoS and Scopus, respectively. This study shows that there are only 13 civil law journals in WoS, while the situation is only slightly better in Scopus. That is why the civil law colleges are ranked much lower in the Shanghai rankings and still very low in the Times Higher Education rankings. This study, in particular, indicates that there are a low number of civil law journals published in languages other than English. Thereby, the most important civil law journals are excluded from the evaluation, and the rankings of civil law colleges are not accurate. The study further focuses on the number of journals included in the WoS and Scopus in a specific area of civil and commercial law. It shows that several core legal areas of civil and commercial law either are not covered at all in WoS and Scopus or are available in very few journals that publish legal research only in the English language. It further reveals that very few languages other than English are represented in WoS and Scopus in the civil law area, and some important civil law nations are not represented by a single law journal publishing in their official languages. This research aims to provide suggestions for university rankings and academic databases on how to evaluate civil law research more appropriately.

Immune checkpoint inhibitors (ICI) have had a dramatic effect on cancer outcomes with their use increasing as indications expand. Despite impressive efficacy across a range of tumour types, their role in activating the immune system results in frequent immune-related adverse events (irAE). While gastrointestinal, endocrine, respiratory and cutaneous toxicities are common, neurological irAEs (N-irAEs) occur more rarely. N-irAEs have been well reported in the literature, can affect any part of the nervous system and are associated with significant morbidity and mortality. Treating oncologists have a high index of suspicion for irAEs and a low threshold for initiating treatment. The role of the neurologist is to consider the differential diagnosis, direct investigation according to the clinical syndrome and guide management, efficacy monitoring and rehabilitation. Once alternative aetiologies have been excluded, the ICI should be either paused or discontinued depending on clinical severity, and immunosuppressive treatment commenced. There is no high-level evidence for toxicity management in this emerging field, so there is much variation in clinical practice and the medical literature. While describing the range of neurological toxicities related to ICIs and current experience of management and outcome, this review focuses on the potential utility of predictive biomarkers, the risk of re-ignition of pre-existing neurological autoimmune disease and the question of rechallenge after a N-irAE. Given the paucity of data specifically relating to N-irAE, we also discuss cancer outcomes in the context of irAEs and associated immunosuppression and consider some outstanding questions pertinent to ICI-related neurotoxicity and potential future directions for research.

<p><strong>Introduction. </strong>Infection caused by the novel coronavirus (SARSCoV-2) emerged in 2019 in China and rapidly spread worldwide. This highly contagious virus is transmitted primarily through respiratory droplets and may lead to Severe Acute Respiratory Syndrome (SARS). The World Health Organization (WHO) declared Coronavirus Disease 2019 (COVID-19) a global pandemic on March 11, 2020. This study analyzed patients hospitalized at the University Clinical Center of Re<br />public of Srpska (UCC RS) during the first 12 months of the pandemic.<br /><strong>Methods.</strong> Data from all patients with laboratory-confirmed SARSCoV-2 infection, diagnosed using real-time reverse transcription polymerase chain reaction (RT-PCR), were collected between March 2020 and March 2021. Patients were analyzed according to age, sex, severity of clinical presentation, duration of hospitalization, and the outcome.<br /><strong>Results. </strong>One year after the first confirmed COVID-19 case in Republic of Srpska, a total of 5,956 COVID-19&ndash;positive patients were hospitalized, including 3,662 males and 2,294 females. The mean duration of hospitalization was nine days, with a statistically significant difference across clinics (p = 0.001). Patients older than 60 years represented the most prevalent age group. During the observed period, 84.53% of patients recovered, while 15.47% died. Cardiovascular diseases were the most common comorbidities, presented in 24.71% of patients.<br /><strong>Conclusion.</strong> Male patients were more frequently hospitalized than females, with statistically significant sex differences observed only at the Anaesthesia and Intensive Care Clinic (p &lt; 0.05). Patients older than 60 years were more susceptible to severe complications and fatal outcomes, with a predominance of male sex.</p>

Heart failure (HF) and atherosclerosis represent two major cardiovascular diseases that are intricately linked, both contributing significantly to global morbidity, mortality, and healthcare burden. Despite substantial progress in diagnostic methods and therapeutic strategies, the overall impact of these conditions remains considerable. This is largely due to their complex and overlapping pathophysiological mechanisms, persistent residual atherosclerotic risk, and the ongoing challenges associated with implementing guideline-directed medical therapy for HF in routine clinical practice. Recent advancements in the management of diverse HF phenotypes, lipid abnormalities, atherosclerotic cardiovascular disease (ASCVD), and obesity have facilitated the adoption of multidrug regimens. These include β-blockers, renin-angiotensin-aldosterone system inhibitors, sodium-glucose cotransporter 2 (SGLT2) inhibitors, and glucagon-like peptide-1 (GLP-1), which have collectively improved outcomes in HF populations. Lipid-lowering therapy, particularly statins, has demonstrated significant efficacy in reducing ASCVD events and slowing HF progression, as well as lowering the risk of HF-related hospitalizations. Elevated lipoprotein(a) [Lp(a)] has emerged as an independent risk factor for both ASCVD and HF, being associated with increased risk of incident HF, disease progression, hospitalization, and adverse outcomes. However, there remains a lack of conclusive evidence as to whether targeted reduction of Lp(a) leads to a decrease in major adverse cardiovascular events or improves HF incidence or outcomes. In parallel, contemporary therapeutic advances in coronary and peripheral artery revascularization, along with novel pharmacologic treatments for obesity such as GLP-1 receptor agonists including semaglutide and tirzepatide have shown beneficial effects in reducing cardiovascular mortality, HF progression, and body weight, irrespective of HF status. These converging therapeutic strategies underscore the close interrelationship between HF and atherosclerosis. This review aims to elucidate the shared pathophysiological mechanisms linking these conditions and to examine their clinical overlap with ischemic heart disease, cerebrovascular disease, peripheral arterial disease, dyslipidemia, and obesity. A comprehensive understanding of these interrelated cardiovascular entities may offer valuable insights to inform future research directions and optimize the clinical management of patients affected by both HF and atherosclerotic disease.

<p><strong>Introduction. </strong>Optic nerve head drusen (ONHD) is one of the most common congenital disorder of the optic nerve with prevalence from 0,5-2% in general population. Idiopathic intracranial hypertension is a condition that occurs in children, unlike adults, regardless of gender or the presence of obesity. Both conditions in children present on the eye as swelling of the optic disc, which is difficult to distinguish by clinical examination. They are extremely rarely associated.</p> <p><strong>Case report. </strong>A 15-year-old girl was urgently admitted due to decreased vision in both eyes for the past 7 days. Computerized visual field (CVP) testing revealed annular scotoma in both eyes, with a residual of 10 degrees and decreased sensitivity. Fundus examination showed an edematous both ONH. Echo B scan showed highly reflective changes corresponding to drusen in ONH. Acetazolamide 250 mg orally three times a day was introduced into the therapy. Neurological examination and MRI of endocranium was normal. After 3 weeks, VA in both eyes was 0.5 corrected with -0.50 Dsph to 1.0. ONH significant regression with unclear boundaries temporally, superiorly and inferiorly. The follow-up period over the next year, visual acuity was stable, and normal CVP, only slightly unclear boundaries of the ONH.</p> <p><strong>Conclusion. </strong>The diagnosis of optic nerve drusen is possible in children with benign intracranial hypertension. For this reason, it is necessary to thoroughly diagnose the patient in order to start treatment in a timely manner and prevent the development of visual impairment.</p>

<p><strong>Introduction. </strong>This study analyzed the factors influencing the outcome of assisted reproductive technology (ART) in women with infertility issues. The investigation focused on endometrial thickness, the number of retrieved oocytes, and the number of obtained embryos as potential predictors of ART success.<br /><strong>Method.</strong> A health-epidemiological questionnaire of general data was created for the purposes of this study. Various statistical methods were applied for data analysis. Descriptive statistical parameters for the observed parameters were pre<br />sented, including the arithmetic mean (M), standard deviation (SD), skewness (Sk), and kurtosis (Ku), to examine deviations from the normal distribution. Multiple regression analysis was applied to investigate the relationships of the independent variables with the dependent variable.<br /><strong>Results. </strong>The study included 100 women of reproductive age. Endometrial thickness was not a significant predictor of ART&nbsp;<br />outcome. Conversely, the number of retrieved oocytes and the number of obtained embryos were identified as significant predictors of ART success. Participants with positive ART outcomes demonstrated a lower number of retrieved oocytes&nbsp;<br />but a higher number of obtained embryos.<br /><strong>Conclusion.</strong> These findings highlight the importance of embryo quality in the implantation process. Further research is&nbsp;<br />needed to better understand this dynamic and to improve infertility treatments.</p>

<p><strong>Introduction. </strong>Pressure ulcers are frequent complications among immobile neurological patients, particularly those with stroke. Nursing knowledge and consistent implementation of preventive measures play a crucial role in reducing their occurrence. The aims of this study are to assess nurses&rsquo; knowledge, attitudes and self-reported competence in pressure ulcer prevention and care, and to describe the prevalence and short-term healing outcomes of pressure ulcers&nbsp;<br />among hospitalized stroke patients.<br /><strong>Methods.</strong> A descriptive cross-sectional study was conducted among 40 nurses/medical technicians using a structured, non-validated questionnaire. Medical records of 375 consecutively hospitalized patients with ischemic or hemorrhagic stroke were reviewed to determine the occurrence and management of pressure ulcers.<br /><strong>Results. </strong>Nurses demonstrated good knowledge of fundamental preventive principles, although gaps were identified in epidemiology and recognition of certain complications. Pressure ulcers were documented in both ischemic and hemorrhagic stroke patients, with an overall prevalence of 5.1%. Conservative treatment was most frequently applied, and most ulcers were recorded as healed at discharge.<br /><strong>Conclusion.</strong> Nursing knowledge appears generally adequate, but specific gaps indicate the need for targeted educational interventions. Interpretation of prevalence and outcomes is limited by the absence of validated assessment instruments and standardized documentation.</p>