Search Results (3,494)

Epstein–Barr virus (EBV)-positive primary central nervous system lymphoma (PCNSL) is a rare entity typically associated with profound immunosuppression, most commonly in transplant recipients or individuals with HIV. We report a case of EBV-positive PCNSL arising in a 75-year-old male with myasthenia gravis receiving chronic mycophenolate mofetil (MMF) therapy outside the transplant setting. The patient presented with progressive neurological deficits, and brain magnetic resonance imaging demonstrated multiple enhancing lesions. Stereotactic biopsy revealed diffuse large B-cell lymphoma of non–germinal center subtype with immunoblastic features and EBV-encoded RNA (EBER) positivity, confirming EBV-positive PCNSL. MMF was discontinued, and the patient was treated with rituximab and high-dose methotrexate, resulting in stable disease. This case highlights that prolonged MMF therapy may confer sufficient immunosuppression to permit EBV-driven lymphoproliferative disease even in non-transplant patients. Early recognition, withdrawal of immunosuppression, and initiation of methotrexate-based chemotherapy can lead to favorable outcomes. Full article

Groundwater in arid and semi-arid regions is increasingly stressed by low rainfall, high evaporation, population growth, agricultural expansion, and climate change. A critical question is whether non-renewable aquifers can sustain rising water demand without irreversible decline. This study addresses that question for the Al Kufrah Basin in southeastern Libya, part of the Nubian Sandstone Aquifer System, the world’s largest fossil aquifer. A three-dimensional groundwater flow model (MODFLOW-2000) was calibrated using data from more than 1000 production wells and 32 piezometers spanning 1968–2022. The model was applied to simulate groundwater behavior under five scenarios extending to 2050, including the planned development of 150 new wells. The results indicate that over 85% of withdrawals are derived from aquifer storage rather than boundary inflows. While regional water levels remain relatively stable over the 25-year horizon, localized drawdowns of up to 11 m are expected near new well fields. These findings highlight short-term resilience but point to long-term vulnerability, as continued reliance on non-renewable reserves without recharge will ultimately lead to depletion. The study underscores the need for adaptive management, climate-resilient water strategies, and regional cooperation to ensure the sustainable use of this transboundary aquifer under increasing environmental and socio-economic pressures. Full article

Inclusive education (IE) aims to promote meaningful participation and a sense of belonging for all learners. However, limited research has examined how students with learning difficulties (LDs) experience inclusion in everyday school life. This study explored how primary school students with mild LDs perceive their participation, relationships with teachers and peers, and the role of inclusive classes (ICs) within mainstream Greek primary education. A qualitative design was adopted, and data were collected through semi-structured interviews with ten Grade 6 students receiving support through ICs. Transcripts were analyzed using thematic analysis. Findings indicated that participation was associated with perceived competence in academic tasks, with language-based activities frequently described as cognitively demanding and stressful. Belonging was predominantly felt through peer acceptance and supportive teacher practices rather than solely through classroom placement. The ICs were perceived as providing individualized support and emotional safety, although some ambivalence regarding withdrawal from the mainstream classroom was reported. Students stressed the need for flexible assessment and clearer instructional guidance to enhance fairness and participation. Overall, the findings show that inclusion is experienced as a dynamic interaction between academic accessibility, interpersonal relationships, and supportive learning environments. They also underline the importance of incorporating student voice into inclusive practice. Full article

Background and Objectives: Postoperative pain and intra-abdominal adhesions are common complications following surgery. Pain delays early mobilization, whereas adhesions can lead to bowel obstruction, chronic pain, or infertility. Current treatments, including systemic analgesics and physical barrier methods, are only partially effective. We hypothesized that combining these modalities would yield superior outcomes. Accordingly, we investigated whether a lidocaine-loaded alginate–carboxymethyl cellulose–polyethylene oxide (ACPE) electrospun film could more effectively reduce both postoperative pain and adhesion formation than either component alone. Materials and Methods: An electrospun nanofiber film composed of ACPE containing lidocaine was prepared. Its effects were evaluated in rats using an incisional pain and a peritoneal adhesion model. Four groups were compared: saline control, free lidocaine, drug-free ACPE film, and lidocaine-loaded ACPE film. Fifteen rats were allocated to each group. The primary outcome was the mechanical withdrawal threshold (MWT) after plantar incision, while secondary outcomes included histological changes and adhesion scores assessed by the Moreno system. Results: The lidocaine–ACPE film significantly increased MWT compared with all other groups, demonstrating a stronger and longer-lasting analgesic effect than free lidocaine. Adhesion scores were also lowest in the film group. Histological analysis confirmed a reduction in inflammatory cell infiltration and collagen deposition. Conclusions: A lidocaine-loaded ACPE nanofiber film effectively reduced both postoperative pain and adhesion formation in a rodent model. The combination of sustained local drug release and physical barrier function provides a promising strategy to address two major postoperative complications. Further preclinical studies are warranted before clinical application. Full article

Rapid renewal and tourism-driven commercialization intensify tensions between heritage conservation and redevelopment in historic districts, and decision-oriented tool chains that translate Historic Urban Landscape (HUL) layering into change management remain limited. Taking Chengdu’s Kuanzhai Alley and Daci Temple historic districts as comparative cases, this study traces four benchmark time slices (1911, 1933, 1994, and 2025) using georeferenced historical maps, remote-sensing imagery, planning base maps, archival documents, and field checks. An auditable morphological-evidence coding manual is developed for street–alley skeletons, plot integrity, redevelopment intensity, interface commodification, connectivity, and heritage-anchor integrity, and it is triangulated with resident-population and commercial-mix evidence to interpret regeneration mechanisms. The results show that morphological continuity can coexist with social discontinuity. Kuanzhai Alley retains a legible street–alley backbone, while plot/operational consolidation and intensive commodification coincide with resident withdrawal. The Daci Temple district experiences broader street–plot reconfiguration and upscale clustering that heightens landmark visibility but challenges contextual integrity and community continuity. Based on these mechanisms, four renewal zoning prototypes and zone-specific monitoring indicator domains are proposed to operationalize HUL’s feedback loop and to support balanced governance of heritage, everyday life, and sustainable urban heritage tourism. Full article

Background/Objective: This study evaluated the analgesic and anti-inflammatory effects of ambroxol in an experimental model of endometriosis. Methods: Ambroxol was administered at doses of 10, 50, and 100 mg/kg (Abx 10, Abx 50, and Abx 100) by daily gavage for 21 days. A medroxyprogesterone-treated group (Progesterone) was included as a positive control. Pain was assessed using validated behavioral tests, including the Rat Grimace Scale (RGS), the von Frey test, and the rotarod test. Additionally, interleukin-1β (IL-1β) levels and total leukocyte counts were measured in peritoneal lavage fluid. The volumetric reduction in endometriotic implants was evaluated by ultrasonography, while histopathological analysis characterized inflammatory infiltrate and epithelial layer integrity using a standardized scoring system. Results: All ambroxol doses reduced spontaneous pain manifestations throughout the treatment. The mechanical withdrawal threshold significantly increased from the second week onward, and motor quality improved over the course of the study. A significant reduction in IL-1β levels compared with the negative control (Control(−)) was observed on day 21. Abx 50 and Abx 100 significantly reduced implant volumes (48.2% and 56.2%, respectively) and promoted marked disruption of the endometriotic epithelial layer. When compared with Progesterone, higher doses—particularly 100 mg/kg—demonstrated comparable efficacy. Conclusions: Taken together, these pleiotropic effects support the potential for drug repurposing in endometriosis. Full article

Di(hetero) aryl and alicyclic amine derivatives of thieno[2,3-b]pyridine were synthesized in good to high yields (45–76%) via palladium-catalyzed Buchwald–Hartwig amination. The reactions were performed using methyl 5-bromothieno[2,3-b]pyridine-2-carboxylate, prepared in this work, and a variety of substituted anilines bearing either electron-donating groups (EDGs) or electron-withdrawing groups (EWGs), as well as pyridinyl amines, and saturated heterocyclic amines such as morpholine and piperidine. For most substrates, the optimal conditions involved Pd(OAc)₂, rac-BINAP, and Cs₂CO₃ in toluene at 100 °C under argon. Substrate bearing EWGs and electron-deficient pyridinyl amines required Xantphos as the ligand, while reactions with piperidine were only successful using Pd₂(dba)₃ as a palladium (0) source. The antiparasitic activity of the synthesized compounds was evaluated against Trypanosoma brucei (T. brucei) and Leishmania infantum (L. infantum) in both promastigote and amastigote forms. Most compounds exhibited no significant cytotoxicity (CC₅₀ > 100 μM) in PMA-differentiated THP-1 derived macrophage cells. Analysis of substituent effects focusing on the nature of amino substitution at position C(5) revealed distinct trends in antiparasitic activity. Notably, one compound exhibited activity against Leishmania infantum promastigotes that was nearly four times higher than that of the reference drug miltefosine, and its selectivity index was also approximately fourfold higher. Full article

Liquid hydrogen (LH₂) fuel system architectures for aviation remain at low Technology Readiness Levels (TRLs) due to limited experimental data and the challenges of modelling cryogenic hydrogen’s behavior. This paper presents a computationally efficient framework for sensitivity analysis that integrates cryogenic thermodynamics, tank geometry, external heat ingress, engine mass flow demands, and pressurization control strategies. A set of operational scenarios was modeled to demonstrate how tank pressure and temperature evolve under various control and geometric conditions, delivering five key insights: (1) Passive tank self-pressurization leads to continuous pressure rise and subcooled liquid. (2) LH₂ withdrawal alone may not fully stop pressurization with high heat ingress. (3) Gaseous hydrogen (GH₂) injection stabilizes pressure only up to moderate heat ingress during LH₂ extraction. (4) The addition of venting enables full pressure control. (5) Tank geometry and heat flux govern transient behavior. Spherical tanks show slower pressure and temperature rise than cylindrical ones, and both geometries maintain near-constant pressure at low heat flux. These insights offer practical guidance for designing reliable and thermally stable LH₂ storage systems for future aircraft applications, paving the way towards sustainable and zero-emission aviation. Full article

This study examines how the COVID-19 period is associated with changes in digital payment usage, rather than simply whether adoption increased, in Saudi Arabia using monthly data from January 2019 to July 2025. An Interrupted Time Series (ITS) approach is employed to assess both the immediate and long-term effects associated with the pandemic on a digital payment Intensity (DPI) index constructed from national point-of-sale (POS) transaction data to capture aggregate electronic payment usage relative to cash withdrawals. The results show that the onset of the COVID-19 period is associated with a sharp and statistically significant one-time increase of approximately 7 to 13% in digital payment intensity, followed by stabilization at a higher level rather than sustained acceleration. This finding challenges the common view that digital payment adoption followed a continuously accelerating path, instead showing that the pandemic induced a discrete upward shift without altering the underlying growth trajectory. The estimated effects remain robust across multiple model specifications, including dynamic ITS models, seasonal adjustments, alternative break dates, exclusion of overlapping usage variables, and parsimonious infrastructure-only models. Inflation and ATM usage consistently show negative associations with digital payment intensity, highlighting the role of macroeconomic stability and cash substitution in shaping payment behavior. The study therefore offers a more nuanced interpretation of post-pandemic digital adoption by showing that the main effect of COVID-19 was a one-time level shift rather than a lasting change in growth dynamics. Focusing on aggregate usage intensity rather than access or account ownership, it provides a system-level perspective on digital payment behavior in response to large-scale shocks. Overall, the evidence suggests that the pandemic period coincided with a discrete upward realignment in digital payment usage in Saudi Arabia, reflecting the interaction between crisis-driven behavioral change and strong pre-existing digital infrastructure under Vision 2030. Full article

Background/Objectives: Adolescent obesity is increasingly recognized as a multidimensional condition involving psychosocial and behavioral vulnerabilities beyond metabolic risk. Although social withdrawal, dysregulated eating behaviors, and sleep disturbances have each been associated with obesity, integrative studies examining these domains concurrently remain limited. This study aimed to comparatively evaluate social withdrawal characteristics, eating behavior patterns, and daytime sleepiness in adolescents with obesity and normal-weight peers. Methods: This cross-sectional case–control study included 209 adolescents aged 14–18 years (100 with obesity; 109 normal-weight controls). Social withdrawal was assessed using the Hikikomori Risk Inventory (HRI-24), eating behaviors with the Children’s Three-Factor Eating Questionnaire (CTFEQ-17), and daytime sleepiness with the Pediatric Daytime Sleepiness Scale (PDSS). The BMI z-scores were calculated according to the CDC growth charts. Group comparisons and correlation analyses were performed. Results: Adolescents with obesity demonstrated significantly higher total social withdrawal scores and higher anthropophobia, agoraphobia, lethargy, and depressive mood subscale scores compared with the controls (all p < 0.01). Uncontrolled eating and emotional eating were also significantly higher in the obesity group (both p < 0.001), whereas cognitive restraint did not differ between groups (p > 0.05). Daytime sleepiness scores were higher in adolescents with obesity (p < 0.01). The BMI z-scores were positively correlated with social withdrawal dimensions and dysregulated eating behaviors (r = 0.15–0.30, p < 0.05) but not with daytime sleepiness. In contrast, daytime sleepiness was moderately associated with social withdrawal and uncontrolled/emotional eating (all p < 0.001). Conclusions: Adolescent obesity is associated not only with maladaptive eating behaviors but also with broader psychosocial vulnerabilities, including social withdrawal tendencies and sleep-related difficulties. These findings support a biopsychosocial conceptualization of adolescent obesity and underscore the importance of multidimensional intervention approaches targeting emotional regulation, sleep hygiene, and social functioning alongside weight management strategies. Full article

Since agriculture sustains most Cambodian households, food safety in the aquaculture and poultry sectors is a public health priority. This study investigates food safety practices and compliance with legal provisions through interviews with 20 participants across four provinces (Battambang, Siem Reap, Kampong Speu, and Takeo). The findings revealed critical deficiencies in hygiene, veterinary medical product management, and traceability. In addition to a detailed qualitative thematic analysis, Structural Equation Modelling identified veterinary drug control (β = 0.670, p < 0.001) and hygiene practices (β = 0.395, p < 0.001) as significant predictors of farm safety. While knowledge positively correlates with these practices, operational challenges negatively impact compliance (β = −0.466 and −0.497, p < 0.005). Notably, fish farmers reported using human medications (e.g., paracetamol) and often neglecting withdrawal periods due to limited VMP access and insufficient knowhow. While acknowledging the pilot-scale sample size, the findings of our modelling complement our qualitative analysis and provide a foundational model for future research. These findings suggest that farmer knowledge and systemic barriers are the primary drivers of food safety outcomes. The study highlights the urgent need for targeted training in good practices and responsible VMP use. Future research should explore scalable interventions to enhance regulatory compliance among smallholder farmers. Full article

This article examines how ancient Greek tragedy mobilizes landscape to reflect on the limits of civic order and the conditions of human dwelling. Rather than treating mountains, groves, meadows, and borderlands as neutral settings or as simple “nature/culture” oppositions, it argues that tragic landscapes are ethically charged spaces where human norms meet forces that exceed political regulation—divine presence, necessity, vulnerability, and finitude. Written for the polis yet unsettled by what lies beyond it, tragedy repeatedly turns to extra-civic spaces to test civic stability. Three case studies develop the argument. In Hippolytus, woodland and meadow sustain an ideal of purity grounded in withdrawal, an orientation incompatible with social life and culminating in catastrophic isolation. In Bacchae, Pentheus’ project of spatial control collapses as Dionysian forces traverse walls and institutions with ease, exposing the limits of civic rationality. In Oedipus Tyrannus and Oedipus at Colonus, the tragic trajectory moves from Mount Cithaeron, a site of abandonment and opaque necessity, to the sacred grove at Colonus, where prolonged suffering enables a transformed relation to place, law, and divine power. Taken together, these plays suggest that the polis is never fully self-sufficient: civic order endures only through engagement with what it cannot master or expel, and spatial orientation is inseparable from ethical choice. Full article

Introduction: Caffeine is the most widely consumed psychoactive stimulant worldwide and acts primarily through antagonism of adenosine A1 and A2A receptors, thereby reducing sleep pressure and promoting wakefulness. Although its alerting and performance-enhancing effects are well established, its influence on sleep-related electroencephalography (EEG) has been investigated across diverse paradigms with substantial methodological heterogeneity. This systematic and mechanistic review aimed to synthesize human evidence on how caffeine affects sleep architecture, quantitative sleep EEG, and neurophysiological markers of sleep homeostasis, and to interpret these findings within current models of adenosine-mediated sleep–wake regulation. Materials and Methods: A systematic search of PubMed/MEDLINE, Web of Science, Scopus, Embase, PsycINFO, ResearchGate, and Google Scholar was conducted for studies published between January 1980 and January 2026, with the final search performed on 10 January 2026. Eligible studies were original human investigations examining caffeine exposure or administration and reporting sleep-related EEG outcomes, including polysomnographic sleep staging, spectral EEG analyses, or other EEG-derived sleep metrics. Two reviewers independently screened records and assessed eligibility, with disagreements resolved by consensus. Data on study design, participant characteristics, caffeine interventions, EEG methodology, and outcomes were extracted using a predefined form. Risk of bias was evaluated using the RoB 2 and ROBINS-I tools. Owing to marked heterogeneity across studies, findings were synthesized narratively within a mechanistic interpretive framework. Results: Thirty-two studies were included. Across highly heterogeneous paradigms—including acute bedtime or evening dosing, daytime or repeated caffeine use before nocturnal sleep, administration during prolonged wakefulness followed by recovery sleep, withdrawal protocols, and ambulatory/home EEG monitoring—the most consistent finding was suppression of low-frequency NREM EEG activity, particularly slow-wave activity and the lowest delta frequencies. Caffeine frequently increased faster EEG activity, including sigma/spindle and beta ranges, producing a lighter, more aroused, and more wake-like sleep EEG profile. These effects were especially prominent during early-night NREM sleep and in recovery sleep after sleep deprivation, where caffeine attenuated the expected homeostatic rebound in low-frequency power. REM-related effects were less consistent, but some studies reported delayed REM timing and subtler alterations in REM EEG. Emerging evidence further suggests that caffeine increases EEG complexity and shifts sleep dynamics toward a more excitation-dominant state. Several studies indicated that quantitative EEG measures were more sensitive than conventional sleep-stage variables in detecting caffeine-related sleep disruption. Dose, timing, habitual caffeine use, withdrawal state, age, circadian context, and adenosinergic genetic variation, particularly involving ADORA2A, moderated the magnitude of effects. We also highlighted the connection between current results and sports and sports science. Conclusions: Caffeine reliably alters the neurophysiological architecture of human sleep in a direction consistent with reduced sleep depth and weakened homeostatic recovery. The overall evidence supports a mechanistic model centered on adenosine receptor antagonism, attenuation of sleep-pressure build-up and expression, and a shift toward greater cortical arousal during sleep. Sleep EEG appears to be a sensitive marker of these effects, often revealing physiological disruption even when conventional sleep architecture changes are modest. Future research should prioritize larger and more diverse samples, pharmacokinetic and pharmacogenetic characterization, and ecologically valid high-resolution sleep monitoring to clarify the real-world and functional consequences of caffeine-induced EEG changes. Full article

Background/Objectives: Staphylococcus aureus (S. aureus) intramammary infection remains a major global dairy problem due to its contagious nature, its ability to persist and colonize teat/skin and mucosal niches, and the often-limited bacteriological cure achieved with antimicrobial therapy. Beyond udder health, it is relevant to public health because it can enter raw milk chains and serve as a reservoir for antimicrobial resistance determinants that may circulate between dairy animals and humans. Methods: We assessed S. aureus’ ecology in raw ewe milk from 75 sheep farms in Epirus (Greece) by sampling clinically healthy controls (group A) and clinical mastitis cases pre-treatment (group B), followed by resampling at the first post-withdrawal milking after penicillin/streptomycin treatment (group C1—therapeutic protocol 1), oxytetracycline treatment (group C2—therapeutic protocol 2), or enrofloxacin treatment (group C3—therapeutic protocol 3). Results: S. aureus detection was high and comparable across groups (A 23.0%, B 22.0–30.0%, C 20.0–22.0%), and paired analyses showed no significant pre–post shifts in detection/burden within therapeutic protocols (all p > 0.05). Nevertheless, persistence remained evident. The chromosomal gene mecA was detected in S. aureus strains in all groups, ranging from 13.6% in controls to 54.5% post-withdrawal in group C1, and was also present in the pre-treatment group. In paired sampling animals, mecA was mostly stable, with rare emergence or loss. Across antibiotic classes, within-animal resistance transitions were generally uncommon and non-significant (p > 0.05); β-lactam resistance was fully stable (p = 1.00). Descriptively, resistance to protein synthesis inhibitors tended to decline after therapy in protocol 1 and protocol 3, while protocol 3 showed post-treatment gains in fluoroquinolone resistance. By contrast, virulence-associated phenotype traits shifted after therapy: enterotoxigenicity increased post-withdrawal (especially in the C3 group), Staphylococcal Enterotoxin A (SEA) and Staphylococcal Enterotoxin B (SEB) appeared only post-therapy, Staphylococcal Enterotoxin D (SED) increased significantly in paired isolates (p = 0.002), and strong biofilm adherence increased (in C3, p = 1.5 × 10⁻⁵). Conclusions: The detection of S. aureus after therapy suggests that one possibility is that antimicrobial exposure may select for, or otherwise reshape, the residual intramammary population, rather than reliably eliminating it—an outcome that remains clinically relevant for udder health. Moreover, the persistence of mecA/methicillin-resistant Staphylococcus aureus (MRSA)-compatible profiles indicates that milk released to the food chain after withdrawal compliance may still harbor S. aureus with enhanced preservation capacity and significant food safety relevance. Full article

Gestational diabetes mellitus (GDM) is a prevalent metabolic disorder associated with adverse maternal and fetal outcomes. However, current diagnostic strategies have a limited capacity to identify women at risk early in pregnancy. In this longitudinal prospective pilot study, 200 pregnant Mexican women were recruited at 11–14 weeks and underwent follow-up throughout pregnancy. Of these, 34 women (19 with GDM and 15 with normal glucose tolerance [NGT]) completed follow-up and were included in the final analyses. Most withdrawals were due to logistical constraints, although the reduced final sample size should be considered when interpreting generalizability. Nine serum proteins (ADIPOQ, AFM, FABP4, IGFBP-5, PAPP-A, PAPP-A2, RBP4, RETN, SHBG) were measured simultaneously using an antibody array and subsequently validated by ELISA. FABP4 showed the greatest increase in the first trimester (4.9-fold, p = 0.0105) and the highest apparent discriminative performance (AUC = 0.91), which declined in the second and third trimesters. Exploratory, hypothesis-generating multivariable analyses suggested a stronger association when FABP4 was combined with gravidity and serum triglycerides (AUC up to 0.97). Overall, FABP4 emerged as a promising candidate biomarker for early GDM detection in Mexican women; however, these findings are preliminary and require validation in larger, independent cohorts to support early risk stratification. Full article