Search Results (1,042)

Empirical management of acute pyelonephritis in Eastern Europe is increasingly constrained by extended-spectrum β-lactamase (ESBL)-producing Enterobacterales and by uropathogen phenotypes—such as strong biofilm formation—which may further blunt antimicrobial activity. We aimed to characterise resistance mechanisms, minimum inhibitory concentration (MIC) distributions, biofilm-forming capacity, and the in vitro performance of carbapenem-sparing agents and to test whether these microbiological features improve prediction of clinical failure beyond standard bedside risk scores. We retrospectively analysed 102 Enterobacterales isolates recovered from 129 consecutive culture-confirmed adult pyelonephritis admissions at “Victor Babeș” University Hospital, Timișoara (March 2022–March 2025). MIC values were determined by Vitek 2 and interpreted using EUCAST v13 breakpoints; ESBL, AmpC, and carbapenemase phenotypes were confirmed by combination disk and modified carbapenem inactivation methods. Biofilm formation was quantified by the microtiter-plate crystal-violet assay. Mediation, Restricted Mean Survival Time (RMST), and decision-curve analyses were used to assess added clinical value. ESBL was confirmed in 30/102 (29.4%) isolates, AmpC in 9 (8.8%), and carbapenemase in 4 (3.9%). ESBL+ isolates were more often strong biofilm formers (33.3% vs. 12.5%; p = 0.014) and showed a 4- to 16-fold rightward MIC shift for cefepime, piperacillin–tazobactam, and ciprofloxacin. Among carbapenem-sparing agents, ceftazidime–avibactam (96.7% S), fosfomycin (80.0% S), and amikacin (73.3% S) retained the highest activity against ESBL+ isolates. Strong biofilm formation and the ESBL phenotype were independently associated with worse outcomes (adjusted OR 3.5 and 4.7); an exploratory mediation analysis suggested that biofilm formation may explain part of the observed association between the ESBL phenotype and treatment failure and that delayed effective therapy may account for a further portion of this association. A microbiology-enhanced model that added the ESBL phenotype, biofilm strength, and acquisition setting to routine clinical variables improved discrimination over a clinical-only baseline (AUC 0.89 vs. 0.71) and showed a higher net benefit on exploratory decision-curve analysis across the 10–40% threshold range. These predictive findings derive from a single-centre cohort with a small number of events and were only internally validated; they require validation in independent cohorts before any clinical application can be considered. The ESBL phenotype and strong biofilm formation were each independently associated with worse outcomes in pyelonephritis and may help identify candidate isolates for carbapenem-sparing strategies anchored on ceftazidime–avibactam, fosfomycin, and amikacin; given the observational, single-centre design, these associations should be regarded as hypothesis-generating. Full article

Viruses cause a great number of infectious diseases with medical, veterinary, agricultural, social and economic impact. Their unique mechanisms to spread, overcome and resist the existing countermeasures require innovative and smart antiviral strategies such as the effective disinfection of enclosed environments with ensured broad-spectrum efficacy and minimized risks associated with handling liquid biocides. Formic acid (FA) is a well-established natural acaricide used in beehives with an antiviral potential; however, its application in a liquid form is hindered by severe corrosiveness and rapid, uncontrolled evaporation. This study describes a novel formulation of FA, using a cryogel carrier for achieving a vapor-phase inactivation of viruses, thus eliminating the need for direct contact between the disinfectant and the pathogen. Firstly, a poly(N-isopropylacrylamide) (PNIPAm) cryogel was synthesized by a procedure involving cryogenic treatment, photochemical crosslinking, and freeze-drying, and then the cryogel was swollen with 65% FA or _ddH₂O as a control. After an exposure of a panel of animal and human viruses to FA, evaporated by the polymer carrier for time intervals between 15 min and 12 h, they were neutralized completely as follows: Poliovirus (PV) as a surrogate for major bee viral pathogens for 60 min by 5.1 ∆lg; Feline calicivirus (FCV) for 60 min by 5.3 ∆lg; Adenovirus 5 (AdV5) for 12 h by 4.0 ∆lg; and Influenza virus A (IAV) for 15 min by 5.1 ∆lg. Results were recorded after titration, 48–72 h incubation, cytopathic effect estimation and NR uptake assay. Our results suggest that 65% FA, when delivered via the PNIPAm cryogel matrix, acts as a powerful agent for fumigation-like disinfection. This “dry” delivery strategy offers significant practical advantages: it eliminates the need for open liquid containers, prevents spill-related hazards, and provides an alternative for controlled, long-term release of active vapors. Full article

Introduction: Schizophrenia is characterised by distributed abnormalities in electrophysiological dynamics and large-scale brain networks, yet unimodal EEG or MRI alone cannot fully explain how fast neural computations relate to spatially organised circuit dysfunction. Multimodal EEG–MRI approaches offer a bridge across temporal and anatomical scales by explicitly modelling cross-modal coupling. Methods: Following PRISMA 2020 guidance, we conducted a systematic, mechanistic review of human studies (adults ≥ 18 years) comparing schizophrenia-spectrum groups with healthy controls using EEG combined with at least one MRI modality (fMRI, structural MRI, and/or diffusion MRI) and explicit EEG–MRI integration (e.g., EEG-informed fMRI, joint ICA, mCCA/MCCA, coupled matrix–tensor factorisation, DCM-based fusion). Searches were performed in PubMed/MEDLINE, Embase, Web of Science, Scopus, PsycINFO, IEEE Xplore, ResearchGate, and Google Scholar for January 2000–December 2025, supplemented by citation tracking. Risk of bias was assessed with ROBINS-I, and due to heterogeneity, results were synthesised narratively by integration of families. Results: From 148 records, 23 studies met the inclusion criteria. Studies used mainly simultaneous EEG–fMRI at 3T and spanned resting-state designs and task paradigms dominated by auditory processing (oddball, MMN/N100–P200, ASSR/aeGBR), with additional work in affective context, working memory, semantic processing (N400), sensory gating, and pharmacologic challenge. Across tasks, the most reproducible multimodal signature was disrupted coupling between electrophysiological markers and the recruitment of large-scale networks, rather than isolated changes in EEG or fMRI metrics. Target detection/oddball paradigms converged on reduced late ERP responses (especially P300, sometimes N2) alongside reduced expression or loss of coupling to salience/ventral attention and control circuitry (including ACC/anterior insula/TPJ). Resting-state studies most consistently indicated altered “coupling rules” (frequency specificity, timing/lag structure, and directionality), including abnormalities detectable even when unimodal summaries were weak. Extended multimodal studies (adding sMRI/DTI and/or classification) suggested that combining modalities can improve discrimination, though performance was sensitive to sample size, demographic imbalance, and feature-selection/validation choices. Conclusions: Multimodal EEG–MRI studies support schizophrenia as a disorder involving persistent structural and circuit-level abnormalities whose functional expression varies dynamically across cognitive states and task demands. Future progress will depend on harmonised acquisition/artefact-control practices for simultaneous EEG–fMRI, larger and more diverse samples (including early/CHR and longitudinal designs), and cross-site replication of mechanistically interpretable coupling biomarkers. Full article

Biologic and targeted synthetic therapies have substantially improved the management of autoimmune diseases (ADs), achieving unprecedented disease control. However, by modulating key immune pathways, these agents increase susceptibility to a wide spectrum of infections. This narrative review synthesizes current evidence on infectious risks associated with biologic DMARDs (bDMARDs) and targeted synthetic DMARDs (tsDMARDs) in AD, characterizing infection profiles across different drug classes, identifying patient- and treatment-related risk factors, and providing evidence-based recommendations for screening, prevention, and management. A comprehensive literature search was conducted through March 2026, across PubMed, Embase, and the Cochrane Library, using predefined search terms combining biologic and targeted synthetic drug classes with infection-related outcomes. Evidence from major international registries (BSRBR-RA, DANBIO, RABBIT) and society guidelines (ACR, EULAR, IDSA) was prioritized. Among bDMARDs, TNF-α inhibitors (TNF-α i) and rituximab were associated with the highest rates of serious infections, whereas IL-17 and IL-23 inhibitors demonstrated comparatively lower infectious risk profiles. Steroids, older age, and prior serious infections emerged as the most consistent patient-related risk modifiers. Unlike prior reviews focused on single diseases or drug classes, this work provides an integrated, cross-disciplinary risk stratification framework. bDMARDs and tsDMARDs remain among the most innovative treatments available for effective management of ADs, with favorable benefit–risk profiles when accompanied by systematic prevention strategies. Universal pre-treatment screening for tuberculosis and viral hepatitis, risk-stratified parasitic screening, evidence-based vaccination, and selective antimicrobial prophylaxis can mitigate infectious complications. Full article

Architectural, urban design, and planning practices are increasingly expected to demonstrate measurable impact, accountability, and responsiveness to complex environmental and social challenges. Evidence-based design (EBD) and research-informed design (RID), which ground design decisions in systematically gathered and critically evaluated knowledge, offer a structured pathway to bridge research and practice. Despite growing recognition, however, EBD and RID remain unevenly integrated across professional practice, particularly within small and medium-sized enterprises (SMEs), which constitute the majority of firms in Europe. This paper explores how SMEs understand, adopt, and operationalize research within architectural, urban design, and planning processes, while identifying the factors that enable or constrain the integration of research into practice. Drawing on a qualitative multiple-case study of four European firms located in Cyprus, Portugal, Italy, and Croatia the study uses semi-structured interviews and thematic analysis supported by AI-assisted coding to identify patterns in how systematic research is understood, enacted and positioned in everyday SME practices. The findings show that research integration depends less on firm size than on the interplay between client expectations, organizational culture, and professional ideology. Practices span a spectrum ranging from ad hoc, compliance-oriented, and project-specific inquiry to strategically embedded and, in one case, activist research-led modes. While research engagement can enhance credibility, efficiency, and innovation, persistent barriers—including limited resources, client resistance, deficient knowledge-management routines, and the absence of shared evaluative frameworks—continue to hinder systematic adoption. Building on the cross-case analysis, the paper proposes a conceptual framework of different modes of research integration in SMEs, offering a heuristic lens for understanding how organizational and contextual factors shape the uptake of research in design practice. The findings contribute to ongoing discussions on practice-based research and highlight the need for more context-sensitive approaches to research integration in small and medium-sized design firms. Full article

Alzheimer’s disease (AD) is a major type of cognitive impairment. Most existing studies on cognitive state classification focus on the direct application of various machine learning (ML) algorithms. These studies typically assume consistency in patient features across assessments, without explicitly accounting for the variability introduced by subjective evaluation. While a limited number of studies have attempted to address such variability, their applicability remains constrained. This study addresses the identified gap by proposing a distribution–coherent data refinement method. First, it incorporates SHAP-based feature selection, then excludes a subset of distributionally atypical records. These include records from patients with a single visit that contribute to increased intra-class variance and reduced inter-class separability, as well as records from patients with multiple visits that exhibit inconsistent longitudinal trajectories. The method operates on the training data, and the resulting refined training data is fed to ML algorithms. The experimental results show that detecting a small number of records (1.285%) leads to a minor enhancement in data quality. The Fisher score and Cohen’s f are increased by on average 0.016 and 0.011, while the means for inter-class and intra-class are improved by 0.012 and 0.004, respectively. Furthermore, the refined training data enables ML models to achieve a higher joint correctness rate of up to 7.1% compared with the original data. Additionally, ML models trained on the refined data exhibit improved classification performance, as reflected by an increase in the $F_1$ score. Therefore, the proposed method provides a potential data refinement strategy for the longitudinal restricted cognitive impairment spectrum, specifically for those data describing normal cognition, early mild cognitive impairment, and late mild cognitive impairment. Full article

The occiput posterior (OP) fetal head position is the most common malposition during labor and is associated with prolonged labor, operative delivery, and cesarean section. Conventional assessment often relies on digital examination, and the clinical significance of OP may lie along a spectrum rather than as a binary diagnosis. The Artificial Intelligence Dystocia Algorithm (AIDA) integrates four objective intrapartum ultrasound parameters (Angle of Progression [AoP], Head–Symphysis Distance [HSD], Midline Angle [MLA], and Asynclitism Degree [AD]) into a five-class ordinal classification (Classes 0–4). This investigation is a focused secondary subgroup analysis of 79 OP cases drawn from a single-cohort dataset of 135 nulliparous women with prolonged second-stage labor originally collected for the development of the AIDA. Only Branch 1 of the AIDA (the deterministic threshold-based classification, with cut-offs originally derived via Decision Tree on the parent cohort, N = 135) was applied; Branch 2 (the case-level machine-learning predictors) was not used, and no predictive model was trained or validated in this study. Cesarean delivery rates rose monotonically across AIDA classes, from no cesareans in Class 0 to all cases delivering by cesarean in Class 4, with a clear gradient across intermediate classes; full numerical results, confidence intervals, and effect sizes are reported in the Results section. Because the AIDA thresholds were derived from the same parent cohort, the analysis is best interpreted as a within-cohort subgroup evaluation rather than as independent validation. The observed class-graded outcome distribution is consistent with the hypothesis that in OP labors, the AIDA class assignment itself may carry clinically relevant information on the risk of intrapartum cesarean delivery; this remains hypothesis generating, and confirmation in independent prospective cohorts is required before AIDA-class assignment can be regarded as an established risk-stratification descriptor in OP labors. Full article

Retinal neurovascular unit (RNVU) dysfunction underlies major blinding and neurodegenerative conditions including glaucoma, diabetic retinopathy (DR), age-related macular degeneration (AMD), retinal ischemia–reperfusion (RIR) injury, and Alzheimer’s disease (AD)-associated retinopathy. Within the RNVU, calcium ions coordinate neurotransmission, glial activation, vascular tone, and blood–retinal barrier maintenance, and calcium dysregulation is emerging as a unifying pathogenic hub across these conditions. Although upstream triggers differ, including mechanical stress in glaucoma, hyperglycemia in DR, oxidative damage in AMD, ischemic energy failure in RIR, and amyloid-β–driven endoplasmic reticulum stress in AD, all converge on disruption of intracellular calcium homeostasis, producing shared downstream consequences including excitotoxic injury of retinal ganglion cells (RGCs), Müller cell reactive gliosis, and pericyte hypercontraction. Broad-spectrum calcium channel blockade has shown limited clinical success, underscoring the need for cell-type-specific and pathway-selective approaches. This review therefore catalogs key interventional nodes, including transient receptor potential (TRP) channel antagonists, T-type calcium channel inhibitors, calcium/calmodulin-dependent protein kinase II (CaMKII) suppressors, and mitochondrial permeability transition pore (mPTP) inhibitors, and discusses how precision targeting of these pathways may restore RNVU homeostasis and open a therapeutic window into central nervous system (CNS) degenerative disorders. Full article

The study proposes and investigates a seismic retrofitting strategy based on an external reinforced concrete exoskeleton, grounded in the analysis of the actual force transfer mechanisms between the existing structure and the added system. The three-dimensional numerical model was developed in ETABS, employing linear response spectrum analysis in accordance with EN 1998-1 and P100-1/2013. The internal forces transmitted at the structural interface were determined using the Section Cut method, enabling the identification of integrated resultants and the prioritization of critical connections. Three types of connections are examined—slab-to-slab, column-to-wall, and beam-to-joint—while the distribution of stresses within the anchor groups is assessed based on an elastic model under combined axial force and bending action. The results indicate that the global structural response is governed by diaphragm coupling, whereas the vertical interfaces ensure kinematic compatibility and the redistribution of axial and bending effects. The proposed methodology provides a coherent framework for the rational design of interface connections in retrofit interventions carried out without interrupting building operation. Full article

Background: Atopic dermatitis (AD) is a chronic, relapsing inflammatory dermatosis that is characterized by pruritus, xerosis, and age-dependent clinical heterogeneity. Accurately diagnosing AD remains challenging due to the absence of specific biomarkers and the broad spectrum of conditions that may mimic its presentation. A wide range of inflammatory, infectious, and genetic disorders resemble AD, including seborrheic dermatitis, psoriasis, contact dermatitis, scabies, dermatophytosis, and nummular eczema, as well as rare immunodeficiency and metabolic conditions. This review summarizes the evolution of the clinical features of pediatric AD across infancy, childhood, and adolescence, with a focus on key differential diagnoses. Recognizing age-specific patterns and potential mimickers is essential for improving diagnostic accuracy and guiding appropriate management in pediatric AD. Methods: This study was designed as a narrative review. A structured literature search was conducted of PubMed/MEDLINE for studies published between January 2001 and March 2026 using predefined keywords related to AD, childhood, diagnosis, and differential. Clinical trials, randomized controlled trials, systematic reviews, meta-analyses, and guidelines or consensus documents were included. Studies focusing exclusively on adults or lacking clinical relevance were excluded. A qualitative synthesis was performed due to the heterogeneity in study designs and outcomes. Results: This review demonstrates that pediatric atopic dermatitis exhibits marked age-dependent clinical heterogeneity, with distinct morphological features and lesion distribution patterns across infancy, childhood, and adolescence. Furthermore, the substantial clinical overlap with a broad spectrum of inflammatory, infectious, and genetic disorders—combined with the absence of specific diagnostic biomarkers—significantly complicates accurate differential diagnosis and increases the risk of misclassification. Conclusions: The recognition of age-specific patterns and potential mimickers is essential for improving diagnostic accuracy and guiding appropriate management in pediatric AD. Full article

Fault-crossing ground motions, characterized by velocity pulses, permanent fault dis-placement, and non-uniform support excitation associated with fault rupture, may significantly affect the seismic performance of siphon bridges crossing active faults. This study investigates a long-span siphon arch bridge subjected to pulse-type fault-crossing ground motions. A unified stochastic ground motion model is developed by integrating nonstationary high-frequency components based on the evolutionary power spectrum with low-frequency pulse components represented by an improved Gabor wavelet, capturing forward directivity effects, permanent displacement, and differential support input at the two sides of the fault. A three-dimensional nonlinear finite element model is established in OpenSees using fiber-based beam–column elements, with hydrodynamic effects incorporated through the added mass method. Parametric analyses consider pulse phase angle (0–90°), amplitude (Mw 6.0–7.5), and frequency (0–1 Hz). Results indicate that structural responses decrease with increasing phase angle, with 0° being most unfavorable, high-lighting the dominant influence of permanent displacement. Resonance amplification occurs when pulse frequencies approach the fundamental modes of the pier (0.345 Hz) and deck (0.51 Hz), while the arch is particularly sensitive near 0.439 Hz. Water added mass reduces natural frequencies by 8–14% and significantly amplifies internal forces. These findings provide guidance for seismic design of fault-crossing siphon bridges. Full article

This paper presents a comprehensive investigation of the impact of I/Q (In-phase/Quadrature) imbalance on the performance of a six-port receiver operating in the millimeter-wave band, specifically in the 60–65 GHz frequency range. Unlike traditional heterodyne architectures, the six-port junction offers a low-cost and low-power alternative for direct conversion; however, it is highly sensitive to hardware imperfections. This study demonstrates that manufacturing tolerances in passive components, such as 90° hybrid couplers and power dividers, introduce significant amplitude and phase disparities. These imbalances geometrically distort the ideal QPSK constellation, transforming the circular decision boundaries into an elliptical profile. The research methodology employs a robust co-simulation approach in Advanced Design System (ADS), integrating measured S-parameters with mathematical analysis to quantify signal degradation. Performance is evaluated using the Error Vector Magnitude (EVM) metric. The experimental findings reveal that even at the higher end of the spectrum (65 GHz), where the amplitude imbalance reaches 0.7 dB and the phase error is approximately 5°, the six-port QPSK receiver maintains an EVM of 8.7%. This result is comfortably below the 17.5% limit mandated by modern wireless communication standards, such as LTE and 5G. These results confirm the architectural resilience of the six-port receiver, validating its effectiveness as a reliable solution for high-speed, short-range data transmission in future ultra-wideband telecommunication infrastructures. Full article

Endogenous estrogens are implicated in carcinogenesis through both estrogen receptor-mediated cell proliferation and the direct genotoxicity of reactive metabolites. Oxidative metabolism of estrogens produces catechol estrogens that are further converted to electrophilic ortho-quinones capable of alkylating DNA. The prevailing model of mutagenesis proposes that these N3Ade and N7Gua adducts depurinate to form abasic sites that induce mutations initiating hormone-related cancers. However, the mutation spectrum observed in experimental data is inconsistent with this mechanism, and synthetic studies of estrogen-DNA adducts have relied on acidic conditions that artificially promote depurination, leaving stable N7-dG lesions poorly understood. To address this, we synthesized stable N7-dG catechol and estrone adducts using 2′-fluorinated deoxyguanosine, a modification that inhibits N-glycosidic bond cleavage. ROESY 2D NMR spectroscopy revealed through-space correlations consistent with a preferred anti-conformation in solution, supported by molecular modeling. Structural analysis suggests that these cationic aryl adducts likely preserve the Watson–Crick base pairing edge but may promote tautomerization capable of altering base pairing and generating G-to-A mutations. These findings provide the first synthesized stable models of N7-dG estrogen adducts and may support an alternative mechanism of estrogen-induced mutagenesis independent of depurination, enabling future biochemical investigations of related DNA repair and mutagenesis. Full article

Hydrodistillation of aromatic plants for essential oil production generates substantial amounts of solid and liquid residues that are commonly discarded despite their potential value as sources of bioactive compounds. In this study, the essential oil and post-distillation residues of Rhododendron tomentosum Harmaja were evaluated within a waste-to-value framework to recover phenolic compounds with antioxidant and antimicrobial properties. Dry extracts obtained from liquid (DEA) and solid (DEE) residues were characterized in terms of total phenolic and flavonoid contents, antioxidant capacity (DPPH assays), and antimicrobial activity against selected microorganisms. Quantitative HPLC–PDA analysis revealed multiple phenolic compounds. Extracts derived from solid residues exhibited significantly higher phenolic and flavonoid contents and stronger antioxidant activity than those obtained from liquid residues, indicating that solid by-products constitute a richer phenolic matrix. Antimicrobial assays revealed pronounced activity for extracts prepared from plant material harvested in October, particularly those based on propylene glycol and glycerin, which were effective against both Gram-positive bacteria and selected Gram-negative clinical isolates. The essential oil showed broad-spectrum antimicrobial activity, including inhibition of Aspergillus niger. Stability studies demonstrated that the phenolic composition and bioactivity of the dry extracts were largely preserved after one year of storage. These findings demonstrate that R. tomentosum hydrodistillation residues represent a promising source of natural antioxidants and antimicrobial agents, supporting their potential utilization as value-added ingredients in food and cosmetic applications and contributing to circular economy strategies. Full article

Background: Non-syndromic retinitis pigmentosa (RP) is characterized by rod–cone degeneration, resulting in night blindness, visual field constriction, and eventual blindness. Recessively inherited RP is predominantly exacerbated in consanguineous populations, such as Pakistan. This study aimed to perform the genetic analysis of sixteen non-syndromic RP segregating Pakistani families, and to summarize the mutation spectrum of non-syndromic RP in our population by reviewing related literature. Methods: We screened 16 non-syndromic RP families using targeted capture panel sequencing of 344 genes related to inherited retinal dystrophies. Variants were prioritized based on rarity (minor allele frequency (MAF) < 0.001 in the gnomAD South Asian subset), pathogenicity assessments using ACMG/AMP criteria, and REVEL scores (>0.5). Candidate variants were validated for familial segregation through Sanger sequencing. Results: We identified 15 distinct variants across 14 genes associated with non-syndromic retinitis pigmentosa, comprising 6 missense, 7 nonsense, 1 frameshift, and 2 splice-site variants, including 4 novel variants, i.e., p.(Val220Met) and p.(Pro1282SerfsTer2) in RP1, 1 each in PDE6B (c.2021+5G>A), and PRCD p.(Ser38Ter). Homozygosity predominated, underscoring the impact of consanguinity on the burden of autosomal recessive disease in the present cohort, while the CERKL disease-causing mutation, i.e., p.(Arg257Ter), recurred in two families. Conclusions: This study expands Pakistan’s non-syndromic RP mutational spectrum by identifying novel variants in RP1, PDE6B, and PRCD, alongside recurrent CERKL and RHO mutations of the local population. The literature review suggests that RP1, TULP1, and PDE6B are among the most mutated genes in our population, supporting the value of population-specific genetic panels to enhance diagnostics and carrier screening. Full article