Search Results (37,410)

Background/Objectives: Previous studies have demonstrated the safety of pre-seasonal treatment with the mannan-conjugated birch pollen allergoid EP-088-T502. However, the safety of a combined pre- and co-seasonal treatment regimen has not yet been investigated. As climate change is associated with earlier and less predictable onset of birch pollen seasons, planned pre-seasonal allergen immunotherapy may unintentionally overlap with natural pollen exposure. Therefore, evaluation of the safety of treatment administered during the pollen season is of increasing clinical relevance. This study aimed to compare, in a purely descriptive manner, the safety and tolerability of pre-seasonal versus pre- and co-seasonal treatment with EP-088-T502. Methods: In this prospective, open-label, phase III trial (T502-SIT-059) (EudraCT No.: 2022-004082-20), patients (N = 109) who had participated in a preceding pivotal phase III study were offered continuation treatment with active EP-088-T502 (10,000 mTU/mL) across five treatment visits. For the subgroup analysis, all patients who completed their last treatment visit before 9 April 2023 (and, thus, before the start of the birch pollen season in Germany) were assigned to the pre-seasonal group (N = 20). Those who performed the last treatment visit thereafter were assigned to the pre-/co-seasonal group (N = 83). Due to post hoc subgroup allocation and unequal subgroup sizes, all subgroup analyses were purely descriptive. Results: No deaths nor serious adverse events (SAEs) were reported during the study. No epinephrine administration was required. Systemic adverse drug reactions (SADRs, N = 3) occurred in two patients who had previously received placebo. No grade III or IV systemic reactions, according to the German AWMF classification, were observed. Patients receiving pre- and co-seasonal treatment developed smaller wheals (mean diameter) compared with the pre-seasonal group (immediate reactions: 0.6 vs. 0.7 cm; late-phase reactions: 0.3 vs. 0.4 cm at the last treatment visit). This was also reflected in the medians (immediate reactions: 0.2 cm vs. 0.4 cm; late-phase reactions: 0.2 vs. 0 cm at the last treatment visit). Of all AEs that were (possibly) related to EP-088-T502 (N = 89), 74 (83%) occurred at the first three treatment visits (before the birch pollen season). The frequency of AEs appeared descriptively similar between groups for the last two treatment visits. Patients who had received placebo in the previous trial experienced more treatment-related side effects compared to patients who had already received EP-088-T502 in the previous year. Conclusions: These data suggest that EP-088-T502 is safe and well-tolerated, even when administered during the birch pollen season, regardless of prior exposure to EP-088-T502. Full article

Background and Clinical Significance: Cantú syndrome (OMIM #239850) is a rare autosomal dominant disorder caused by gain-of-function variants in ABCC9 or KCNJ8, which encode subunits of the ATP-sensitive potassium (K_ATP) channel. Its characteristic features—generalized hypertrichosis, coarse facial appearance, skeletal abnormalities, and cardiovascular involvement—may be overlooked when other major comorbidities dominate the clinical picture. Case Presentation: A 29-year-old Taiwanese woman, born prematurely and complicated by neonatal hydrocephalus with subdural hemorrhage requiring ventriculoperitoneal shunt placement, had been followed since infancy under a working diagnosis of cerebral palsy with left hemiparesis and borderline-to-mild intellectual disability. Over the ensuing years, additional features gradually emerged, including generalized hypertrichosis with thick scalp and body hair, coarse facial features, bilateral hallux valgus, mild thoracic scoliosis, polycystic ovaries, mild aortic regurgitation, recurrent hemoptysis associated with abnormal pulmonary vasculature, and iron-deficiency anemia. Earlier genetic investigations—including chromosome analysis (46,XX), array comparative genomic hybridization (array-CGH; 2013), and a trio-based next-generation sequencing study performed under a national rare disease research initiative (2019)—were unrevealing. Whole-genome sequencing performed in December 2025 identified a heterozygous ABCC9 variant (NM_020297.4:c.4174A>G, p.(Ile1392Val)), initially classified as a variant of uncertain significance. Parental Sanger sequencing confirmed the variant to be de novo, and reclassification according to ACMG/AMP criteria supported a likely pathogenic interpretation. Re-evaluation of the patient’s phenotype demonstrated findings consistent with Cantú syndrome. Conclusions: This case illustrates how Cantú syndrome may remain unrecognized for years when a prominent neurological comorbidity—perinatally acquired hydrocephalus and presumed cerebral palsy—dominates the clinical narrative. We report a previously undescribed de novo ABCC9 missense variant (c.4174A>G, p.(Ile1392Val)), thereby expanding the mutational spectrum associated with Cantú syndrome. This case also highlights the practical value of resequencing and periodic reanalysis using updated next-generation sequencing platforms in patients with long-standing undiagnosed disease, even after prior negative genetic testing. Full article

Recent studies suggest coccidioidomycosis can be found outside regions not considered to be endemic for Coccidioides species. We reviewed our experience with coccidioidomycosis at a large quaternary medical center in southeastern Michigan, an area not typically considered to be endemic for this infection. In the last decade, we cared for 18 patients with proven (11) or probable (7) coccidioidomycosis. All patients had a history of travel or prior residence in areas known to be endemic for Coccidioides species; for 16, the presumed source of exposure to Coccidioides was in southern Arizona. The median age was 64 (36–80) years. Thirteen patients had pulmonary coccidioidomycosis; manifestations included multiple lung nodules, consolidated pneumonia, diffuse reticulonodular infiltrates, chronic thick-walled cavitary lesions, and pleural involvement. Five patients had disseminated infection, including two with isolated coccidioidal meningitis, one with osteoarticular coccidioidomycosis, one with extra-thoracic lymphadenopathy in addition to diffuse lung infiltrates, and one with involvement of lung, mediastinal lymph nodes, and skin. Proven coccidioidomycosis was established by growth of Coccidioides species in culture in five patients, histopathological examination in five patients (one of whom also had a positive culture), and positive complement fixation (CF) test for Coccidioides antibody in cerebrospinal fluid for two patients. Probable coccidioidomycosis was documented for seven patients by positive titers for CF antibody to Coccidioides in serum. A careful travel and exposure history remains crucial for patients presenting outside Coccidioides-endemic regions, in which coccidioidomycosis may not be readily suspected and the diagnosis missed. Full article

This study relates to the growing recognition of the school–family relationship as a key factor in equity, inclusion, and educational success, highlighting the need to strengthen teacher education in this area. The aim was to design and content validate a specific instrument for identifying teachers’ training needs in relation to the promotion of this relationship. The EVANEFEF questionnaire was developed from a prior qualitative study and subsequently subjected to content validation by an expert panel of eleven specialists, followed by a pilot study. The final instrument, comprising 114 items on prior training and the self-assessment of competencies related to the school–family relationship, showed adequate content validity. The findings indicate that the questionnaire enables the assessment of teachers’ perceptions and the identification of training needs in key areas such as communicative, digital, socio-emotional, and multicultural competencies. In conclusion, EVANEFEF is a useful tool for guiding the design of teacher-training programmes that are more closely aligned with actual needs, thereby strengthening school–family collaboration and, ultimately, improving educational quality. Full article

Background. Vaccinations are highly effective in preventing infectious diseases, which otherwise present a serious challenge to the health of individuals and public health. To identify potential gaps in vaccination coverage, we examined childhood vaccination levels in Frankfurt am Main (FFM) and the Rhein Neckar district (including Heidelberg city, RNHD) prior to, during and following the COVID-19 pandemic. Moreover, we explored various factors that appear to contribute to lower vaccination levels in specific communities in either or both locations. The results are intended to guide strategies for designing and improving vaccination services for specific groups in local health settings. Methods. A retrospective analysis was conducted to examine the vaccination rates of children in Frankfurt am Main and the Rhein Neckar district (including Heidelberg city) by using anonymized data from school entry examinations spanning the years 2017 to 2024. Data pre-processing, analysis, and visualization were performed using R (5.4.2). Frequencies and percentages were calculated for sociodemographic and vaccination rates (the completeness of the vaccination schedule recommended by STIKO for children). Multivariate logistic regression was performed to determine factors with a significant impact on vaccination uptake. Results. Multinomial logistic regression with ‘measles-only’ (Measles) as the reference category revealed distinct predictor patterns across vaccination levels. In both regions, children who completed preventive medical check-ups had higher odds of completing the schedule of vaccination plus at least one additional vaccine (ScheduledPlus) versus, measles-only vaccination. In RNHD, children from Eastern European language families and low- and medium-social-status backgrounds showed higher odds of completing the scheduled vaccinations without the recently introduced rotavirus vaccination (ScheduledNotRota), versus measles-only vaccination. In FFM, strong interaction effects were observed between medical examination completion and migration background, with children from non-German birthplaces showing dramatically reduced odds of complete vaccination when preventive care was incomplete. Discussion. The proportion of children with a complete vaccination status remained stable over the study period in both locations, with no evidence of post-pandemic decline. Nevertheless, this stability masks important heterogeneity in vaccine coverage patterns across sociodemographic groups. Systematic identification and modeling of interactions between nationality, parental employment, and healthcare utilization tell a compelling “double jeopardy” story that the effects of these risk factors are not additive but synergistic. Regular medical check-ups remain an important factor in ensuring high vaccination coverage among children until they start school and underscore the justification for such established preventive care programs. A nuanced understanding, however, is crucial for moving beyond simplistic, one-size-fits-all public health messaging. Full article

Background/Objectives: The anticoagulant used for blood collection is a fundamental but underexplored variable in platelet-rich plasma (PRP) preparation. Ethylenediaminetetraacetic acid (EDTA) and sodium citrate act on platelets through distinct calcium chelation mechanisms with potentially different consequences for PRP quality. Our group has previously demonstrated that biological and demographic variables independently modulate platelet composition in PRP; the present study extends this analysis to the pre-analytical anticoagulant variable. No prospective paired clinical study has systematically compared the effects of EDTA and sodium citrate on platelet morphological parameters in a real clinical setting. This study aimed to characterise these differences and evaluate their implications for orthobiologic therapy. Methods: A prospective within-subject paired-sample study was conducted at Instituto Cugat—Quirónsalud Barcelona (November 2025–April 2026). Twenty-six consecutive adult patients undergoing routine blood extraction prior to orthopaedic procedures had blood drawn simultaneously into K₂-EDTA and sodium citrate (3.2%) tubes. Full haematological analysis was performed on a Sysmex XN automated analyser within 30 min. Primary outcomes were mean platelet volume (MPV), platelet distribution width (PDW), large platelet ratio (P-LCR), large platelet cell count (P-LCC), and plateletcrit (PCT). Statistical comparisons used the paired t-test or Wilcoxon signed-rank test; effect sizes were quantified as Cohen’s d. Results: Seven of eight platelet-related parameters differed significantly between anticoagulants (all p < 0.001). Compared to sodium citrate, EDTA produced systematically higher MPV (+10.1%, d = 2.81), P-LCR (+25.8%, d = 2.41), P-LCC (+24.3%, d = 1.70), PDW (+13.5%, d = 1.33), PCT (+7.3%, d = 0.78), RDW-CV (+2.0%, d = 0.83), and RDW-SD (+2.6%, d = 0.80). MPV was higher with EDTA in all 26/26 paired samples without exception. Total platelet count did not differ significantly (p = 0.135). Effect sizes for all morphological parameters were large (d ≥ 0.78). Conclusions: EDTA is associated with large, reproducible, and universal platelet morphological changes consistent with calcium chelation-induced artefact, not genuine platelet hypertrophy. These artefactual changes systematically overestimate platelet size and large platelet indices by up to 26%, with direct implications for PRP quality assessment in orthobiologic medicine. Sodium citrate should remain the anticoagulant of choice for PRP preparation. Clinicians using EDTA must recognise that morphological parameters do not reflect functional platelet capacity. Full article

Hormone receptor-positive (HR+), human epidermal growth factor receptor 2-negative (HER2–) metastatic breast cancer (MBC) is the most prevalent subtype of advanced breast cancer and is predominantly driven by estrogen receptor (ER) signaling. Endocrine therapy (ET) has become the backbone of first-line treatment; however, both intrinsic and acquired resistance limit long-term disease control. The introduction of cyclin-dependent kinase 4/6 (CDK4/6) inhibitors has fundamentally reshaped the therapeutic landscape even in subsets of patients with aggressive or symptomatic visceral metastatic disease. Advances in molecular profiling have also enabled more precise, adaptive therapy. Circulating tumor DNA (ctDNA)-based liquid biopsy now allows real-time detection of emerging resistance mutations, particularly in ESR1. Additionally, patients with PIK3CA-mutated tumors who had progressed on or within 12 months of completing adjuvant ET and had no prior systemic therapy for metastatic disease had better treatment outcomes when treated with the PI3K inhibitor inavolisib in combination with palbociclib and fulvestrant. Together, these developments mark a shift from fixed treatment sequencing toward a more dynamic, biomarker-driven approach in first-line HR+/HER2– MBC. Integration of CDK4/6 inhibitors with next-generation endocrine agents and liquid biopsy-guided therapy offers the potential to delay resistance, improve survival outcomes, and individualize treatment. Full article

Ship detection in remote sensing images is crucial for maritime surveillance, port management, and national security. However, existing detectors struggle with complex harbor backgrounds, large-scale variations, and fine-grained inter-class similarities among diverse ship categories. In this paper, we propose SPFDet, a CLIP text-prior-guided structure-enhanced detector that systematically addresses these challenges by integrating vision-language semantic priors with channel-selective feature enhancement. First, a Semantic Prior Component (SPC) employs a frozen CLIP text encoder to generate category-level semantic embeddings from textual descriptions of ship types, which are combined with visual scene priors and detail-aware priors to provide hierarchical domain-specific guidance. Second, a Structure-Enhanced Transformer Module (SETM), equipped with a Cross-level Channel Selection Module (CCSM) and Multi-Head Cross-Attention (MHCA), selectively enhances discriminative channel responses associated with hull contours, deck textures, and fine structural patterns across encoder layers. Third, a Fused Category-Dominated Feature (FCDF) generation mechanism integrates CLIP-based semantic priors with multi-scale visual features through category-guided attention, producing category-aware representations for precise classification and localization. We further introduce a Category-Semantic Consistency Loss to enforce alignment between predicted features and CLIP text priors. Extensive experiments on HRSC2016 and ShipRSImageNet benchmarks demonstrate that SPFDet achieves 97.2% and 72.8% mAP respectively, providing consistent improvements over strong detection baselines while maintaining competitive inference speed. Full article

The acquisition of geophysical data is becoming increasingly important in the context of critical mineral exploration. Geophysical data and inversion products are essential to map many components of the critical mineral system by detecting geophysical anomalies that can be interpreted by expert geologists. However, the inversion of airborne geophysical data acquired along flightlines into subsurface petrophysical properties remains an outstanding challenge. Many inversion techniques rely either on 1D deterministic inversion or on stochastic inversion on a local scale. The outcome of our work is the stochastic inversion along flightlines of 2D panels (flightline direction vs. depth), while at the same time producing plausible spatial variation in the petrophysical properties. Our method relies on a sequential application of Bayesian inversion, where we invert a sequence of 2D panels such that the variation in petrophysical properties avoids generation of artifacts across the panel boundaries. We show that our method can be used in a practical setting in the context of mineral exploration in the Cape Smith Belt of Canada. Full article

Background/Objectives: Adults under legal protection experience management delays and prolonged hospitalization. This study investigated whether ICU outcomes differ between patients with versus without legal protection. Methods: This retrospective, single-center study evaluated patients admitted to a French ICU (July 2015–July 2023). Protected patients were compared to autonomous controls matched 1:3 by age and admission year. Results: Of the 1051 patients included, 266 (25.3%) were under legal protection. The protected group had a higher proportion of women (43.2% vs. 35.7%, p = 0.025), received renal replacement therapy less frequently (8.6% vs. 15.4%, p = 0.007), and required non-invasive ventilation more frequently (25.2% vs. 17.2%, p = 0.004) than controls. Three-month mortality was 38.7% in controls versus 33.1% in protected patients, showing no significant difference after multivariable adjustment for 6 prespecified clinical variables (aOR 0.816, 95% CI 0.564 to 1.180). In the adjusted model, higher SAPS II scores and vasopressor use were significantly associated with increased 3-month mortality, whereas non-invasive ventilation and non-respiratory admission indications (sepsis, renal failure, trauma) were associated with decreased mortality. Conclusions: No significant association was observed between the presence of a legal protection measure prior to ICU admission and 3-month patient mortality. However, these results must be interpreted with caution due to a potential lack of statistical power. Additionally, legally protected patients were observed to receive renal replacement therapy less frequently, whereas non-invasive ventilation was utilized more frequently. Within this context, further research is required to evaluate the impact of legal protection status on the formal collegial deliberations that lead to decisions regarding the limitation of life-sustaining treatments. Full article

Lentinus edodes stipe is an under-utilised processing by-product that holds potential as a natural umami source. This study systematically compared nine enzymatic hydrolysis combinations, including single proteases, cellulase, and double enzyme systems comprising both protease–protease and protease–cellulase mixtures, to optimise the release of taste-active and volatile flavor compounds from the stipes. The Flavourzyme-only hydrolysate achieved the highest degree of hydrolysis (50.38%), the richest 5′-nucleotides (5.46 mg/g), free amino acids (59.06 mg/g) and volatile compounds (150.23 μg/kg), and an equivalent umami concentration of 288 g monosodium glutamate equivalent per 100 g matter. It also delivered the strongest umami taste and the lowest bitterness in sensory evaluation. The double-enzyme systems consistently underperformed due to competitive substrate binding, suboptimal pH for companion enzymes, and potential mutual protease digestion. Among the volatile compounds, 1,2,4-trithiolane and cedrol were identified as key aroma differentiators by multivariate analysis. These findings demonstrate that Flavourzyme alone constitutes the optimal enzymatic system for producing clean-tasting, umami-rich condiments from L. edodes stipes and caution against indiscriminate enzyme blending without prior compatibility assessment. The optimized hydrolysis process provides a scalable route for the industrial valorisation of mushroom processing by-products. Full article

In millimeter-wave frequency-modulated continuous-wave (FMCW) multiple-input multiple-output synthetic-aperture radar (MIMO-SAR) imaging, platform displacement beyond the spatial Nyquist limit during a slow-time sampling interval creates aperture gaps, causing azimuth aliasing and degraded resolution. This paper proposes a spectral-prior-guided Swin TransUnet (SSTU) method for suppressing azimuth ambiguity in sparse moving-array imaging. Gaussian soft labels derived from point-scatterer positions formulate localization as heatmap regression and guide mainlobe learning. A two-dimensional fast Fourier transform (2D-FFT) layer then constructs a range–azimuth spectrum that exposes main peaks, sidelobes, and periodic grating lobes. A convolutional encoder extracts local spectral features, Swin Transformer blocks model long-range ambiguity correlations, and a U-Net-style multiscale decoder reconstructs high-resolution range–azimuth images. Simulations show that SSTU reliably recovers multiple point targets from noise and grating lobes despite substantial aperture gaps. At 60% aperture sparsity and signal-to-noise ratio (SNR) above −6 dB, it achieves a root mean square error (RMSE) below ${10}^{-2}$ and an azimuth ambiguity suppression ratio better than −30 dB, outperforming conventional methods. Measurements using a 77 GHz radar platform further demonstrate high-quality outdoor imaging of randomly distributed strong scatterers at 60% moving-aperture sparsity. Full article

This paper proposes a level-based scientific maturation master plan (SMMP) for strengthening research projects prior to manuscript submission. A weak manuscript is often not simply a weak text but an immature project that has been translated too early into publication form. Contemporary research management is better at registering deadlines, deliverables, resources, and visible publication signals than at diagnosing the internal maturity of a scientific object. The result is false readiness: a project may have a topic, structure, literature, methodological vocabulary, and a polished manuscript but still lack a mature problem, a coherent conceptual architecture, a testable design, sufficient evidence, and a disciplined contribution. To address this gap, this paper proposes a nine-level SMMP, moving from thematic impulses to peer review and publication readiness. The model integrates noncompensatory gates, evidence packages, red flags, maturation debt, bottlenecks, the publication maturation gap, and peer-review readiness. Methodologically, the paper is a conceptual design study supplemented by a proof-of-concept documentary application to publicly available CORDIS project biographies. The framework shows how to distinguish publication polish from scientific maturation and how to translate expert criticism into concrete presubmission actions. Full article

Although CFM is a promising non-thermal stabilization technology for blackberry juice, its industrial application is limited by permeate flux decline during long-term operation, while most previous studies have focused on short processing times. This study evaluated the effect of high-shear homogenization prior to enzymatic depectination on flux decline, product quality, and techno-economic feasibility during CFM. Juice processed by conventional grinding, high-shear homogenization, and enzymatic treatment was filtered through a 0.2-µm ceramic membrane at 150 kPa using feed volumes of 100–400 L. Homogenization reduced particle size and suspended insoluble solids, resulting in higher permeate flux, improved flux stability, and greater productivity. Flux decline analysis showed that high-shear homogenization extended the stable filtration regime and delayed severe fouling, sustaining an average J_px of 65.3 L h⁻¹ m⁻² at VCR ~30 with feed volumes up to 400 L. Product quality was preserved, ensuring microbial reduction while improving anthocyanin and ellagitannin recovery (95% and 80%, respectively) and enhancing blackberry aroma. In addition, HS3+E reduced energy consumption and beverage production cost while achieving a positive NPV and a 21% IRR. Overall, homogenization improved the industrial feasibility of long-term CFM processing of Andean blackberry juice. Full article

Background and Objectives: Red cell distribution width–standard deviation (RDW-SD) has been associated with systemic inflammation and adverse cardiovascular outcomes, but its relationship with the angiographic severity and morphological complexity of drug-eluting stent-in-stent restenosis (ISR) has not been systematically characterized. The present study investigated whether RDW-SD is associated with angiographic restenosis severity and restenotic lesion complexity, and compared its performance with the platelet distribution width (PDW), Metabolic Stress Index (MSI), and Platelet-to-HDL Ratio (PHR). Materials and Methods: In this retrospective single-center observational study, 290 patients undergoing clinically indicated repeat coronary angiography following prior drug-eluting stent (DES) implantation were enrolled. Angiographic luminal narrowing was quantified by QCA and categorized as reference (<50% in-stent luminal narrowing; n = 111), intermediate ISR (50–69%; n = 76), and severe ISR (≥70%; n = 103). The Mehran classification was applied to patients with ISR ≥50% and dichotomized as Mehran class I–II (n = 91) vs. Mehran class III–IV (n = 70). Multivariable logistic regression, hierarchical modeling, and incremental discrimination analyses (IDI and NRI) were performed for both binary outcomes. Results: RDW-SD differed significantly across angiographic severity groups (Kruskal–Wallis H = 51.14, p < 0.001), being highest in the ISR ≥70% group [44.6 fL (IQR 43.8–45.3)] and lowest in the ISR 50–69% group [43.2 fL (42.7–43.7)]. A parallel pattern was observed across Mehran class (H = 50.57, p < 0.001; Mehran class III–IV: 44.9 fL [44.2–45.8]). In multivariable analysis, RDW-SD independently associated with ISR ≥70% (OR = 1.228 per 0.5 fL, 95% CI 1.122–1.344, p < 0.001) and Mehran class III–IV (OR = 1.274, 95% CI 1.155–1.406, p < 0.001). Hierarchical modeling showed that adding RDW-SD improved the AUC from 0.603 to 0.719 for ISR ≥ 70% and from 0.592 to 0.757 for Mehran class III–IV (LRT p < 0.001 for both), with incrementally larger IDI and NRI gains for the Mehran class III–IV outcome. PDW did not retain significance after adjustment; MSI and PHR were not significantly associated with either outcome. Conclusions: RDW-SD was independently associated with both angiographic ISR severity and Mehran morphological complexity in patients with established drug-eluting stent restenosis, with numerically greater model discrimination for the Mehran class III–IV endpoint. These findings suggest that RDW-SD may provide complementary information regarding restenosis burden and complexity in patients with established ISR. Prospective studies are required to validate these observations and determine their clinical relevance. Full article