University of Debrecen

BackgroundBrepocitinib is a first-in-class, oral, selective TYK2–JAK1 inhibitor that blocks cytokine signaling, which has been implicated in dermatomyositis.MethodsIn this phase 3, double-blind, randomized, placebo-controlled trial, adults with dermatomyositis were assigned in a 1:1:1 ratio to receive once-daily oral brepocitinib at a dose of 30 mg, brepocitinib at a dose of 15 mg, or placebo for 52 weeks. Standard therapies were continued, and glucocorticoids were tapered. The primary end point was the Total Improvement Score, a validated composite myositis index (with scores ranging from 0 to 100 and higher scores indicating greater improvement) at week 52. Key secondary end points, including skin disease activity, glucocorticoid tapering, and physical function, were tested in a multiplicity-controlled sequence.ResultsA total of 241 patients underwent randomization: 81 to receive brepocitinib 30 mg, 81 to receive brepocitinib 15 mg, and 79 to receive placebo. At week 52, the mean Total Improvement Score was 46.5, 37.5, and 31.2, respectively (difference with brepocitinib 30 mg vs. placebo, 15.3; 95% confidence interval [CI], 6.7 to 24.0; P<0.001; difference with brepocitinib 15 mg vs. placebo, 6.3; 95% CI, −2.4 to 14.9). Brepocitinib 30 mg was superior to placebo across all nine key secondary end points, including skin disease activity, systemic glucocorticoid tapering, and functional disability, with improvements observed as early as week 4. Serious infections were more frequent in the brepocitinib 30-mg group than in the placebo group (10% vs. 1%). No deaths occurred during the trial.ConclusionsIn adults with dermatomyositis that was resistant to previous therapy, the use of brepocitinib at a dose of 30 mg (but not at a dose of 15 mg) resulted in significant benefits with respect to a composite myositis index, skin disease severity, glucocorticoid tapering, and functional disability. (Funded by Priovant Therapeutics; ClinicalTrials.gov number, NCT05437263.)

To evaluate the efficacy and safety of conservative (oxygen saturation [Sp o2 ] 88-94% or Pa o2 < 80 mm Hg) vs. liberal oxygen targets (Sp o2 ≥ 94% or Pa o2 ≥ 90 mm Hg) in mechanically ventilated critically ill adults. PubMed, Cochrane CENTRAL, Embase, and ClinicalTrials.gov . We conducted the OXY-BREATHES, a systematic review and meta-analysis of randomized controlled trials (RCTs) comparing conservative vs. liberal oxygen targets in mechanically ventilated ICU patients. Primary outcomes were 90-day mortality and ICU length of stay. Secondary outcomes included ventilator- and vasopressor-free days, renal replacement therapy, nosocomial pneumonia, and cardiac or cerebral ischemic events. Subgroup analyses included patients with sepsis/septic shock and post-cardiac arrest. Data were collected according to study selection criteria. Certainty of evidence was appraised with Grading of Recommendations, Assessment, Development, and Evaluation, and risk of bias with the Cochrane tool. Data were analyzed using a random-effects model. Nine RCTs enrolling 20,447 patients were included. Conservative and liberal targets showed no substantial differences in 90-day (risk ratio [RR], 1.01; 95% CI, 0.94-1.09) or ICU length of stay (mean difference [MD], -0.17; 95% CI, -0.41 to 0.06). Secondary outcomes, including organ support-free days and the incidence of adverse events, were comparable between groups. In subgroup analyses, conservative targets yielded more vasopressor-free days in septic patients (MD, 2.0; p = 0.008) and a potential survival benefit in post-cardiac arrest patients (RR, 0.89; p = 0.05). Certainty of evidence was rated moderate for 90-day mortality, ICU length of stay, vasopressor-free days, and ventilator-free days; low for renal replacement therapy and nosocomial pneumonia; and very low for cerebral and cardiac ischemia due to imprecision and open-label trial designs. Conservative oxygenation is comparable to liberal oxygen targets in mechanically ventilated critically ill patients, with possible advantages in sepsis and post-cardiac arrest. Future condition-specific RCTs are warranted to define optimal ICU oxygen strategies.

Purpose The purpose of this study is to examine how gender shapes vacation preferences among Central European leisure travelers, with particular attention to motivational themes, demographic interactions and affective expression. The analysis explores whether women’s and men’s narratives reveal distinct motivational patterns, how gender intersects with education and age in structuring preferences and whether emotional tone differs across gender groups. Design/methodology/approach Open-ended responses from 842 Hungarian leisure travelers were analyzed using a mixed-methods analytic approach integrating qualitative and quantitative techniques within a single data set. Thematic coding identified motivational categories in participants’ narratives, while sentiment analysis assessed affective tone across gender groups. Latent Dirichlet Allocation uncovered underlying semantic patterns separately for male and female respondents. Logistic regression models incorporating post-stratification weights tested whether gender, education and age predicted theme prevalence. This triangulated strategy enabled cross-validation across complementary analytic dimensions. Findings Age emerged as the strongest demographic driver: older participants were markedly more likely to cite Health (p = 0.007) and Relaxation (p = 0.004). Education predicted the New Experiences motive (p = 0.006). Gender differences were modest and limited to routine escape (p = 0.005). Sentiment analysis showed women expressing a broader affective range (stronger positive and negative sentiment than men). Research limitations/implications This study’s reliance on self-reported data and Central European sample limits generalizability. Despite these constraints, findings provide valuable insights into gender–demographics–vacation preference intersections. Practical implications The results of this study offer tourism stakeholders guidance for developing targeted, gender-sensitive offerings aligned with modern vacation preferences. Social implications The findings of this study highlight evolving gender roles’ influence on vacation preferences, emphasizing the need for inclusive, adaptable tourism practices. Originality/value This study demonstrates that in a Central/Eastern-European setting, age and education outweigh binary gender in explaining vacation motives. The mixed-methods analysis reveals nuances not visible through single-method approaches.

Background/Objectives: Radiolabeled bevacizumab-based immuno-PET tracers enable a non-invasive quantification of VEGF-A expression in gynecologic malignancies. While the previously reported [52Mn]Mn-DOTAGA-bevacizumab demonstrated selective VEGF-A-targeted uptake in a KB-3-1 cervix carcinoma mouse model, further improvements in chelator stability and tumor-to-background contrast remain desirable. The recently developed BPPA chelator exhibits exceptionally high Mn(II) complex stability and favorable radiolabeling characteristics. This study aimed to characterize the in vivo biodistribution of [52Mn]Mn-BPPA-bevacizumab, and to compare the tumor-to-background ratios of [52Mn]Mn-BPPA-bevacizumab with the previously published values of [52Mn]Mn-DOTAGA-bevacizumab in VEGF-A-expressing cervix carcinoma. Methods: Female KB-3-1 tumor-bearing CB17 SCID mice underwent PET/MRI imaging following intravenous administration of [52Mn]Mn-BPPA-bevacizumab. SUVmean values were measured in various organs and in the subcutaneously injected tumor, and tumor-to-organ ratios were calculated at various time points up to 10 days post-injection. Results: [52Mn]Mn-BPPA-bevacizumab demonstrated sustained tumor uptake, with tumor SUVmean values increasing from approximately 1.0 at 4 h to peak values of approximately 2.4-2.5 at 72 h post-injection. Tumor-to-background ratios increased progressively over time and were significantly higher for [52Mn]Mn-BPPA-bevacizumab compared with previously reported [52Mn]Mn-DOTAGA-bevacizumab, particularly for tumor-to-blood, tumor-to-liver and tumor-to-lung ratios at later imaging time points (p < 0.0001). Conclusions: The novel [52Mn]Mn-BPPA-bevacizumab tracer exhibits satisfactory in vitro and in vivo stability for PET imaging, high VEGF-A-specific tumor uptake, and markedly improved tumor-to-background ratios compared to the previously published DOTAGA-based probe. These results position [52Mn]Mn-BPPA-bevacizumab as a highly promising next-generation immuno-PET agent for imaging VEGF-A-expressing gynecologic malignancies and for guiding anti-angiogenic therapies.

In arid coastal environments, urban expansion alters land–water interactions, leading to increased soil salinity and moisture accumulation across urban landscapes. This study examines the spatiotemporal evolution of soil salinity and moisture, and land-use/land-cover (LULC) changes in Port Sudan, an arid coastal city that experienced rapid expansion from 2008 to 2024. The limited vegetation cover enables effective shortwave infrared (SWIR)-based assessment of salinity and moisture, facilitating multi-temporal analysis of LULC change and hydro-saline impacts. The findings demonstrate significant landscape transformation driven by urbanization, with built-up areas nearly doubling, substantial rangeland expansion, and a pronounced reduction in bare ground. These land-use transitions are accompanied by a marked inland expansion of salinity and moisture-affected areas, increasing from 8.12 to 40.36 km2 and from 120.15 to 245.49 km2, respectively, particularly within low-lying and reclaimed sabkha terrains. Urban growth exhibits strong correlations with hydro-saline intensification (R2 = 0.77 and 0.82), as increased surface impermeability and disrupted drainage promote salt accumulation and subsurface water retention. Field observations in representative urban areas confirm that persistent hydro-saline ground conditions are linked to salt crust formation, sustained surface moisture, and progressive corrosion of building materials and foundations. Time-series forecasting indicates that continued urbanization is likely to further extend hydro-salinity-affected areas through 2040, with projections suggesting a substantial spatial increase under current development trajectories, although with uncertainty related to environmental variability and temporal resolution. Overall, this study presents a field-calibrated, earth observation-based framework that connects urban expansion with hydro-saline processes and related coastal infrastructure vulnerability, supporting risk-informed planning and management in arid coastal regions. Salinity and Moisture indices successfully mapped across 16 years using multi-sensor datasets. Integrated remote sensing and VES-EC calibration for semi-quantitative salinity assessment. New calibrated SI threshold (110) derived from EC-RS regression and field evidence. Inland expansion of saline and moist soils is linked to rapid urbanization and surface modification. Predictive modeling shows saline-affected areas may exceed 150 km2 by 2040 without mitigation. This graphical abstract demonstrates that rapid urban growth in Port Sudan, a dry coastal city, intensifies hydro-saline processes and increases infrastructure vulnerability. The study employs multiple data sources, including satellite imagery, MODIS land-use records, fieldwork, and electrical resistivity measurements, to provide a comprehensive assessment of soil salinity and moisture dynamics. All datasets are synchronized using atmospheric correction, temporal normalization, and surface reflectance standardization to ensure consistent analysis across 2008-2024. The analytical framework extracts salinity and moisture indicators (SI, NDMI/SMI, LST, LSE) and integrates them with land-use and land-cover (LULC) classification to quantify changes in built-up areas, bare ground, and rangeland. Calibration using 24 Vertical Electrical Sounding points and 6 solar salt sites establishes salinity (SI > 110) and moisture (SMI > 140) thresholds, enabling semi-quantitative interpretation of hydro-saline intensity. The resulting maps reveal an inland expansion of salinity and moisture from coastal sabkha into reclaimed and peri-urban areas, closely associated with increased impervious surfaces and modified drainage patterns. The graphical abstract shows strong correlations between urban expansion and increased salinity and moisture, confirming land-use transformation as a primary driver of hydro-saline intensification. ARIMA time-series modeling projects these trends through 2040, indicating continued expansion of built-up and salinity-affected areas. The final panel links these environmental changes to field observations of salt crusts, waterlogging, corrosion, cracking, and structural deterioration, emphasizing their impact on infrastructure stability.

Background/Objectives: Several therapeutic approaches, including phlebotomy and rheopheresis, are used to improve hemorheological parameters. While the effects of phlebotomy on cerebral circulation have been described, the impact of rheopheresis on cerebral hemodynamics remains poorly understood. This study primarily aimed to evaluate the within-group effects of phlebotomy and rheopheresis on cerebral blood flow velocity changes evoked by neuronal activation and on cerebrovascular reactivity in patients with elevated hematocrit or hyperviscosity, respectively. Methods: In our present study, we used transcranial Doppler to examine the effects of phlebotomy (n = 11) and rheopheresis (n = 9) on cerebral hemodynamics in patients with elevated hematocrit and hyperviscosity, respectively. Measurements included resting flow velocity (FV) in the posterior cerebral artery (PCA) and middle cerebral artery (MCA), the visually evoked FV response in the PCA (neurovascular coupling) and the hypercapnia-induced FV response in the MCA (cerebral vasoreactivity). In addition to flow velocity data, visual evoked potential (VEP) parameters were also recorded to assess neuronal activation. Results: Phlebotomy significantly reduced hematocrit and hemoglobin levels, while rheopheresis led to a significant decrease in both blood and plasma viscosity. Although we observed no differences in resting FV values before and after either intervention, the FV increase in response to visual stimulation and hypercapnia was greater after rheopheresis than before, whereas no such difference was observed following phlebotomy. VEP parameters remained similar before and after both phlebotomy and rheopheresis. Conclusions: Our data indicate that rheopheresis reduces blood and plasma viscosity in patients with hyperviscosity and leads to a significant improvement in cerebral vasoreactivity and neurovascular coupling, without affecting VEP parameters. The improvement in cerebral vasoreactivity, but no changes in VEP parameters, suggests that the improved FV response to visual stimulation after rheopheresis is most likely caused by better vascular response rather than improved neuronal activation.