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K. Sweerts, L. Vork, Z. Mujagic, J. Conchillo, D. Keszthelyi

Purpose Disorders of gut–brain interaction (DGBI) affect up to 40% of people worldwide and in several studies an association with hypermobility spectrum disorders (HSD) was described. HSD patients frequently report gastrointestinal (GI) symptoms and GI dysmotility has been suggested as underlying mechanism. This study evaluates whether individuals with (undiagnosed) joint hypermobility and/or HSD show different GI symptom and motility patterns compared to those without hypermobility/HSD. Methods In this prospective open-label study, patients who were referred for GI motility assessment between 2016 and 2018 were included. Motility assessments included esophageal manometry, gastric emptying test, antro-duodenal manometry, colonic manometry, and/or a colonic transit study. Joint hypermobility was assessed using the Beighton score, and HSD was diagnosed using the Brighton criteria. Symptom severity, anxiety and depression, and quality of life were evaluated through validated questionnaires. Results Eighty-seven participants were included (73 women, median age 42.0 years), and categorized into HSD (n = 23) and non-HSD (n = 64), with further subdivision by Beighton cut-off values (≥ 4, and ≥ 6). GI symptom scores were high, with 37% of the total population exhibiting depressive symptoms (HADS ≥ 8), and 32% experiencing anxiety. Quality of life scores were generally low, with a physical composite score of 26.9 (13.2) and a mental composite score of 47.3 (17.1). Across all comparisons, no significant differences in GI symptoms or motility patterns were found between all groups. Conclusion This exploratory tertiary care study found no distinct GI symptom or dysmotility patterns between patients with and without hypermobility/HSD. Further research is warranted to investigate whether GI dysmotility is related to hypermobility. Supplementary Information The online version contains supplementary material available at 10.1007/s10620-025-09206-5.

Marko Kordić, Davorin Kozomara, I. Mikulić, V. Mikulić, M. Kajić, Miran Boras, Mateo Bevanda, Neven Soldo et al.

Inguinal hernia is a prevalent condition requiring surgical intervention, and accumulating evidence suggests that the type of anesthesia administered may influence systemic inflammatory responses. This study investigates the concentrations of inflammatory parameters in patients with inguinal hernia who underwent surgery utilizing either general or spinal anesthesia. The cohort comprised 87 male patients with inguinal hernia, classified as American Society of Anesthesiologists (ASA) physical status 1-2, who underwent elective surgical procedures. Participants were divided into two groups based on the anesthesia type: 44 received general anesthesia while 43 received spinal anesthesia. Plasma concentrations of leukocytes, C-reactive protein (CRP), interleukin-6 (IL-6), and lipopolysaccharide-binding protein (LBP) were quantified using automated immunoassays and a hematological analyzer. Standard parametric and non-parametric statistical tests were employed for data analysis, and the predictive capacity of select parameters, along with body mass index (BMI) and age, was assessed through Receiver Operating Characteristic (ROC) analysis with Area Under the Curve (AUC). Statistical analysis via the t-test identified significant differences in LBP concentrations (LBP 1, LBP 2, and LBP 3) between patients receiving general and spinal anesthesia. Correlation analysis of BMI and the measured parameters revealed statistically significant positive correlations for LBP 1 and LBP 2 in patients who underwent spinal anesthesia. Notably, the preoperative concentration of LBP, with a cutoff value exceeding 9.7 µg/mL, suggests a potentially superior approach with spinal anesthesia compared to general anesthesia, demonstrating 50% sensitivity and 81.4% specificity. Other parameters did not exhibit statistical significance in differentiating the type of anesthesia used for inguinal hernia surgery.

Sofiya Shamailova, Luiz Alexandre Dalla Vecchia, E. Auer, Pasquale Castigliego, Victor Ziegler, Marc Fluri, Anna Boronylo, M. Kielkopf et al.

Background and Objectives While MRI is known to be crucial for TIA workup, the benefit of perfusion-weighted imaging (PWI) is underexplored. We aimed to assess the association between focal hypoperfusion on baseline PWI MRI and the long-term incidence of subsequent acute ischemic stroke (AIS) after TIA. Methods Consecutive patients with TIA who underwent baseline PWI MRI as part of their emergency consultation between January 2015 and December 2019 were retrospectively identified. For study inclusion, both a time-based (symptom duration <24 hours) and an imaging-based (no signs of ischemia on diffusion-weighted imaging) TIA definition were applied. Long-term incidences of AIS after TIA were identified based on follow-up reports. Associations between focal hypoperfusion and subsequent AIS were assessed using Cox regression models adjusted for predefined predictors of stroke occurrence including symptomatic extracranial or intracranial stenosis. In subgroup analyses, we aimed to determine effects of focal hypoperfusion within vs outside the expected TIA territory, defined as a brain region potentially correlating with TIA symptoms. Results Of 1,359 eligible patients with TIA, 1,075 with PWI MRI (79%) were included (median age 70 years, 46% female). Focal hypoperfusion was identified in 211 patients (20%); in 116 of 211 (55%), hypoperfusion occurred within the expected TIA territory. The median time from symptom onset to imaging was 233 minutes (interquartile range [IQR] 131–632) for patients with focal hypoperfusion vs 229 minutes [IQR 140–441] for patients without (p = 0.42). Focal hypoperfusion was associated with a higher incidence of AIS (adjusted hazard ratio [aHR] 2.13; 95% CI 1.19–3.80). While this was observed for focal hypoperfusion within the expected TIA territory (aHR 3.95; 95% CI 2.05–7.60), there was no such association in case of focal hypoperfusion outside the expected TIA territory (aHR 0.72; 95% CI 0.25–2.03). Discussion Focal hypoperfusion on acute PWI MRI was found in 1 in 5 patients with TIA. It was associated with a higher incidence of AIS during long-term follow-up, especially when within the expected TIA territory. Further research is needed to clarify the predictive value of focal hypoperfusion in relation to the incidence of AIS after TIA and to explore potential therapeutic implications.

Pablo Olgoso, P. Paradisi, Nudžeim Selimović

The future circular $e^+e^-$ collider (FCC-ee or CEPC) will provide unprecedented sensitivity to indirect new physics signals emerging as small deviations from the Standard Model predictions in electroweak precision tests. Assuming new physics scenarios containing a dark matter candidate and a $t$-channel mediator, we analyse the synergy and interplay of future Tera-$Z$ factories and non-collider tests conducted through direct and indirect searches of dark matter. Our results highlight the excellent prospect for a Tera-$Z$ run to indirectly probe the presence and nature of dark matter.

Hamza Preljević, Ena Kazić-Çakar, Mirza Ljubović, Hana Šarkinović-Köse, Harun Halilović, Kenan Ademovic

This article examines the integration challenges faced by foreign workers in Bosnia and Herzegovina, based on qualitative data from 16 workers across various professions. It addresses how these workers perceive integration policies and the legal, bureaucratic, social, and cultural barriers they encounter. With a significant outflow of skilled labor from Bosnia, foreign workers play a crucial role in filling the workforce gaps. The European Migration Network predicts a need for 45 million qualified workers in Western Europe, including Bosnia, by 2030, prompting a high emigration rate from the Western Balkans, which, in turn, will increase the demand for foreign labor. This will, in turn, make it more complex for BiH to fulfill its commitment to the Agenda 2030, as set forth by the United Nations in 2015, through the 17 Sustainable Development Goals (SDGs). A low birth rate contributes to the increasing need to increase the labor force, which may ultimately result in social engineering. Although the number of foreign workers in Bosnia has increased, they experience limited access to integration programs and face social isolation and administrative hurdles, which this article analyzes and aims to emphasize better integration policies. Future studies can explore the social acceptance of foreign workers by the locals in Bosnia.

Introduction With their remarkable flight capabilities, wild and captive birds play a pivotal role in the global dissemination of zoonotic pathogens including Chlamydia psittaci, Avian Influenza viruses (AIV), Chikungunya virus (CHIKV), Usutu virus (USUV), and West Nile virus (WNV). They function both as hosts and reservoirs responsible for transporting the mentioned infectious agents across vast geographic regions. Additionally, captive birds and birds inhabiting urban environments, particularly in tourist destinations, present significant public health concerns due to facilitated close interactions with humans. Methods A total of 358 samples originating from fifteen bird species were collected across 21 locations in Sarajevo Canton, over three consecutive years (2022–2024). Upon collection, the samples were subjected to molecular analysis to detect the presence of zoonotic pathogens. For detection of Chlamydia spp., and C. psittaci, real-time PCRs (qPCR) were used following established protocols. Additionally, reverse transcriptase real-time PCR (RT-qPCR) were utilized for the detection of emergent viral pathogens including avian influenza viruses, Chikungunya, Usutu, and West Nile virus. Results Chlamydia spp. was detected in 29.9% (95% CI: 25.2–34.9) of samples. Further, C. psittaci was identified in 10.3% (95% CI: 5.2–17.7) of positive samples originating from captive birds and birds inhabiting urban environments. One sample (0.3%) originating from a wild bird was positive to West Nile Virus. None of the samples tested positive for Avian Influenza viruses, Chikungunya and Usutu virus. Discussion The identification of C. psittaci and West Nile virus highlights the increased likelihood of zoonotic transmission. This underscores the imperative for bolstered biosecurity measures and public health strategies aimed at mitigating the risk associated with both environmental exposure and direct contact, especially in areas characterized by substantial tourist activity.

M. Goeldlin, Rosa Küttner, Boudewijn Drop, B. Siepen, J. Rauch, E. Auer, A. Hakim, Piotr Radojewski et al.

BACKGROUND AND OBJECTIVES Diffusion-weighted imaging (DWI) lesions in patients with intracerebral hemorrhage (ICH) are associated with poor outcomes. Knowledge about the underlying pathophysiology is scarce, and it is hypothesized that they are related to either the ICH itself, adverse effects of treatment, or the activity of the underlying small vessel disease (SVD) causing the ICH. We investigated their association with time point of MRI acquisition and underlying SVD type and burden. METHODS In this Swiss multicenter ICH cohort, we enrolled patients who underwent MRI within 15 days after SVD-associated ICH. The primary outcome was presence of DWI lesions. Time point of MRI was investigated as a continuous (days) and dichotomized (hyperacute = MRI on admission vs subacute = MRI during follow-up) variable. We measured cerebral amyloid angiopathy (CAA) and SVD severity using MRI burden scores and defined the type of SVD using CADMUS classification and Boston 2.0 criteria. At 3 months, we assessed functional outcome using the modified Rankin Scale score, recurrent ICH, and ischemic stroke. RESULTS We included 644 patients (median age 73 years, interquartile range [IQR] 64-79, median SVD burden 1 IQR 1-2; median CAA burden 2 IQR 1-3; 208 patients/32.3% with Boston 2.0 CAA, 431 patients/66.9% with mixed CAA-DPA phenotype according to CADMUS). Among enrolled patients, 16.0% underwent hyperacute MRI and 84.0% underwent subacute MRI (median on day 2 IQR 1-5), and 166 patients (25.8%) had DWI lesions (18.4% with hyperacute MRI vs 27.2% with subacute MRI). We observed no association of presence of DWI lesions with hyperacute MRI (adjusted odds ratio [aOR] 0.61, 95% CI 0.36-1.00, p = 0.073) but with time to MRI in days (aOR 1.07, 95% CI 1.00-1.13, p = 0.007). Higher SVD (aOR 1.33, 95% CI 1.12-1.59, p = 0.001) and CAA (aOR 1.29, 95% CI 1.15-1.44, p < 0.001) burdens were associated with presence of DWI lesions. There was no association between type of SVD (CADMUS) or CAA (Boston criteria) and DWI lesions. There was no association between DWI lesions and functional outcome, recurrent ICH or ischemic stroke at 3 months. DISCUSSION DWI lesions in patients with ICH are already common at baseline. Their prevalence is higher with a longer time since symptom onset and with higher SVD burden. Overall, these findings suggest a relation with the underlying condition resulting in ICH. The significant number of DWI lesions visible on admission MRI might diminish their use as surrogate outcome in future trials in ICH.

Ivan R. Kennedy, M. Hodzic, A. Crossan

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.

Michael CB David, Emma-Jane Mallas, Lucia M. Li, Magdalena A. Kolanko, R. Nilforooshan, Man Lai Tsoi, Hanim Karakoc, Karen Hoang et al.

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.

T. Meinel, P. Bücke, L. D’Anna, G. Merlino, D. Aguiar de Sousa, Sven Poli, J. Purrucker, D. Strambo et al.

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.

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.

Merjem Be'cirovi'c, Amina Kurtovi'c, Nordin Smajlovi'c, Medina Kapo, Amila Akagi'c

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.

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