Search Results (91)

China and Italy, both ancient civilizations, have numerous traditional villages that bear witness to history and support the transmission of cultural heritage. However, these villages face challenges such as homogenized development, population outflow, and disruptions in cultural continuity. While both Chinese and Italian traditional villages have received considerable scholarly attention, their comparative study remains relatively limited, leaving the transferability of respective solutions across different legal, heritage and planning contexts to be fully explored. This study aims to adapt and transfer Italy’s contiguous protection, integrated operation, national park designation, and community partnership policies to China in order to establish a comprehensive mechanism for preservation and revitalization of traditional villages. A cross-case study of Cinque Terre (Italy) and Jiande (China), incorporating on-site mapping, governance analysis, and interviews, reveals that Italy’s integrated community-based approach markedly outperforms China’s fragmented state-led model in sustaining population, culture and tourism quality. These findings provide a globally replicable paradigm for traditional village preservation. Full article

Underwater vessel localization using passive magnetic anomaly sensing is a challenging problem due to the variability in vessel magnetic signatures and operational conditions. Data-based approaches may fail to generalize even to slightly different conditions. Thus, we propose an Attentive Neural Process (ANP) approach, in order to take advantage of its few-shot capabilities to generalize, for robust localization of underwater vessels based on magnetic anomaly measurements. Our ANP models the mapping from multi-sensor magnetic readings to position as a stochastic function: it cross-attends to a variable-size set of context points and fuses these with a global latent code that captures trajectory-level factors. The decoder outputs a Gaussian over coordinates, providing both point estimates and well-calibrated predictive variance. We validate our approach using a comprehensive dataset of magnetic disturbance fields, covering 64 distinct vessel configurations (combinations of varying hull sizes, submersion depths (water-column height over a seabed array), and total numbers of available sensors). Six magnetometer sensors in a fixed circular arrangement record the magnetic field perturbations as a vessel traverses sinusoidal trajectories. We compare the ANP against baseline multilayer perceptron (MLP) models: (1) base MLPs trained separately on each vessel configuration, and (2) a domain-randomized search (DRS) MLP trained on the aggregate of all configurations to evaluate generalization across domains. The results demonstrate that the ANP achieves superior generalization to new vessel conditions, matching the accuracy of configuration-specific MLPs while providing well-calibrated uncertainty quantification. This uncertainty-aware prediction capability is crucial for real-world deployments, as it can inform adaptive sensing and decision-making. Across various in-distribution scenarios, the ANP halves the mean absolute error versus a domain-randomized MLP (0.43 m vs. 0.84 m). The model is even able to generalize to out-of-distribution data, which means that our approach has the potential to facilitate transferability from offline training to real-world conditions. Full article

Progression of aortic stenosis (AS) is aggravated by type 2 Diabetes Mellitus (T2DM) and kidney dysfunction (KD). Oxidative stress is one of the main mechanisms that triggers AS and is also disturbed among subjects with T2DM and KD. Consequently, we studied the redox homeostasis in four groups of patients, also classifying each patient based on their kidney function: control subjects, T2DM, AS, and AS+T2DM. Free reduced thiols in plasma were analyzed using a colorimetric assay, and the redox state of human serum albumin (HSA) was assessed by immunodetection and PEG-PCMal labeling. Lower levels of thiols were evident in patients with AS and AS+T2DM, while reduced and mildly oxidized HSA was more abundant in T2DM and AS+T2DM patients, reflecting less protection against oxidation. Moreover, the thiol levels decreased as KD increased in patients with AS and AS+T2DM. Differences also exist in reduced and mildly oxidized HSA between patients with normal and severely impaired kidney function, whereas AS patients with severe KD had more strongly oxidized HSA. Our results confirm an imbalance in oxidative stress associated with AS that is aggravated by the coexistence of T2DM and KD. Moreover, T2DM treatment might mitigate this dysfunction, opening the door to new therapeutic approaches for these patients. Full article

Background: Human Immunodeficiency Virus (HIV) infections remain a source of cardiopulmonary complications among people receiving antiretroviral therapy. Still to this day, pulmonary hypertension (PH) severely affects the prognosis in this patient population. The persistent expression of HIV proteins, even during viral suppression, has been implicated in vascular dysfunction; however, little is known about the specific effects of these proteins on the pulmonary vasculature. This study investigates the impact of Nef variants derived from HIV-positive pulmonary hypertensive and normotensive donors on pulmonary vascular cells in vitro. Methods: We utilized well-characterized Nef molecular constructs to examine their effects on cell adhesion molecule gene expression (ICAM1, VCAM1, and SELE), pro-apoptotic gene expression (BAX, BAK), and vasoconstrictive endothelin-1 (EDN1) gene expression in endothelial nitric oxide synthase (eNOS) nitric oxide and the production and secretion of pro-inflammatory cytokines over 24, 48, and 72 h post-transfections with Nef variants. Results: HIV Nef variants SF2, NA7, and PH-associated Fr17 and 3236 induced a significant increase in adhesion molecule gene expression of ICAM1, VCAM1, and SELE. Pulmonary normotensive Nef 1138 decreased ICAM1 gene expression, but had increased VCAM1. PH Nef ItVR showed a consistent decrease in ICAM1 and no changes in SELE and VCAM1 expression. Further gene expression analyses of pro-apoptotic genes BAX and BAK demonstrated that Nef NA7, SF2, normotensive Nef 1138, and PH Nef Fr8, Fr9, Fr17, and 3236 variants significantly increased gene expression for apoptosis. Normotensive Nef 1138, as well as PH Nef Fr9 and ItVR, all displayed a statistically significant decrease in BAX expression. The expression of EDN1 had a statistically significant increase in samples treated with Nef NA7, SF2, normotensive Nef 2044 and PH Nef 3236, Fr17, and Fr8. Notably, PH-associated Nef variants sustained pro-inflammatory cytokine production, including IL-2, IL-4, and TNFα, while anti-inflammatory cytokine levels remained insufficient. Furthermore, eNOS was transiently upregulated by all Nef variants except for normotensive Nef 2044. Conclusions: The distinct effects of Nef variants on pulmonary vascular cell biology highlight the complex interplay between Nef, host factors, and vascular pathogenesis according to the variants. Full article

Upadacitinib has demonstrated efficacy in psoriatic arthritis in clinical trials, but its real-world performance in difficult-to-treat PsA remains underexplored. This observational, multicenter, open-label study evaluated the efficacy and safety of upadacitinib in 134 patients with psoriatic arthritis (97 women, mean age 51.8 ± 11.2 years, mean disease duration 9.94 ± 7.72 years) who showed inadequate response to advanced therapies. Most patients (74.6%) had received at least two biological/targeted synthetic disease-modifying antirheumatic drugs with different mechanisms of action. Upadacitinib was initiated at 15 mg daily, and within one month, significant improvements were observed: DAS28-ESR decreased from 4.7 to 3.77 (p < 0.001), DAPSA from 25 to 17 (p < 0.001), and CRP from 2.90 to 1.50 mg/L (p = 0.001). These reductions persisted throughout the study. Prednisone dosage decreased significantly (p = 0.049). Adverse events led to upadacitinib discontinuation in 8.2% of patients, but no serious adverse events were reported. Compared to the SELECT-PsA 2 trial, our cohort had a higher proportion of females and greater prior exposure to biologic agents but showed comparable efficacy and safety outcomes. These findings suggest that upadacitinib is a rapid, effective, and relatively safe therapeutic option for difficult-to-treat psoriatic arthritis under real-world conditions, supporting its use despite differing patient characteristics from clinical trial populations. Full article

Ergosterol peroxide (EP) triggers apoptosis pathways by inducing reactive oxygen species (ROS) in TNBC cell lines. Excess ROS production is associated with major damage to mitochondria. We hypothesized that EP may act through ROS-induced mitochondrial dysfunction. Therefore, we performed a series of assays that assessed mitochondrial membrane potential (MMP), cellular respiration, and glycolysis in TNBC models. Cardiomyocytes derived from human-induced pluripotent stem cells were chosen as a non-cancerous model because of their high mitochondrial content. Two in vivo TNBC models were used to quantify the effect of EP on tumor volume and metastases. EP reduced MMP and disrupted mitochondrial functions exclusively in TNBC cells. In vivo EP was effective in reducing tumor volume without affecting liver function. There was also a significant decrease in metastasis to the lung, liver, and cancer stem cells following treatment. These results suggest EP is a promising therapy for TNBC. Full article

A new hyphenated technique using thin-layer chromatography (TLC) to separate analytes in mixtures, coupled with mid-infrared (MIR) laser spectroscopy for identification and quantification, is presented. The method, which provides a means for rapid screening of analytes that is practical, low-cost, fast, robust, and reproducible, was tested using nitroaromatic and aliphatic nitro high explosives (HEs) as target analytes. HEs are anthropogenic contaminants containing an -NO₂ group. For validation of the new technique, a direct comparison of the 2,4,6-trinitrotoluene (TNT) spectrum, obtained by attenuated total reflection-Fourier transform infrared (ATR-FTIR) spectroscopy coupled with TLC, was carried out. The MIR laser spectroscopy-based method was evaluated by calculating the analytical figures of merit regarding the calibration curves’ linearity and the method’s sensitivity and precision. The TNT spectrum obtained by the MIR laser method showed two prominent and characteristic bands of the explosive at approximately 1350 cm⁻¹ and 1550 cm⁻¹ compared to the spectrum acquired by ATR-FTIR. The detection limit calculated for TNT was 84 ng, while the quantification limit was 252 ng. Multivariate analysis was used to evaluate the spectroscopic data to identify sources of variation and determine their relation. Partial least squares (PLS) regression analysis and PLS combined with discriminant analysis (PLS-DA) were used for quantification and classification. The new technique, TLC-QCL, is amenable to a smaller footprint with further developments in MIR laser technology, making it portable for fieldwork. Full article

Honey is a multifaceted substance whose composition is intricately affected by various biotic and abiotic elements generated in the bee colony’s surroundings, including botanical and geographical origins, climatic conditions, soil characteristics, and beekeeping techniques. Monofloral honeys are identified by pollen analysis and are derived from the nectar of a predominant plant species, exhibiting rich sensory and nutritional profiles, making them food matrices with unique characteristics and excellent qualities. To explore the monofloral honey potential harvested in different regions of Portugal, a comprehensive study was conducted including the determination of phenolic composition and the assessment of biological activities. In addition to this evaluation, the inter simple sequence repeat (ISSR) was used to help differentiate honeys by botanical origin. The phenolic content and the antioxidant capacity were evaluated by spectrophotometric methods, observing, in general, differences between monofloral honeys. The honey from Citrus sinensis (Silves) exhibited the lowest phenolic content, including total phenols, ortho-diphenols, and flavonoids, whereas honeydew (Vinhais) showed the highest values. Regarding the antioxidant capacity, honey from Lavandula stoechas (Almodôvar) presented the lowest values, while honeydew (Vinhais) displayed the highest values for both DPPH and FRAP assays. In relation to the ABTS assay, the honey from Metrosideros excelsa (Aveiro) exhibited the lowest values, whereas the honey from Eucalyptus spp. (Arouca) showed the highest. The ISSR marker analysis allows the distribution of the samples based on the honey’s botanical origin, suggesting its potential role in honey authentication. Full article

Traditional conservation strategies often prioritize minimizing water use; nevertheless, water can also enhance thermal comfort by incorporating a water-to-air heat exchanger (WAHE) alongside non-direct evaporative and radiant cooling techniques. A WAHE can be installed in features such as ponds, water tanks, or rainwater cisterns. This article assesses the cooling potential of two prototypes of roof ponds and a green roof connected to a WAHE, and the results are compared to a baseline unit featuring a roof that meets California’s energy code standards. Several testing units, measuring 1.35 × 1.35 × 1.35 m, with identical heat characteristics, excluding the roof, were constructed and tested. In the first system, the heat that the green roof could not absorb was transferred to a water reservoir and then dissipated to the outside. The first roof pond prototype features a 0.35 m deep water pond topped with a 0.03 m thick insulating panel and a spray system. The second roof pond variant has an aluminum sheet with a 0.10 m air gap above a 0.25 m deep water pond. The results suggest that combining a WAHE with different roof configurations offers promising benefits while keeping water consumption limited. Notably, when the WAHE is operating, the green roof increase its performance by 47%, the insulated roof pond by 22%, and the roof pond with an aluminum sheet by 13%. Full article

Lung cancer remains the most common malignancy independent of sex. Here, we focused on unraveling the molecular mechanisms of CaS nanoclusters inducing cytotoxicity by investigating DNA damage, the cell cycle, oxidative stress, and cellular repair mechanisms in non-small-cell lung carcinoma (NSCLC) cells compared to healthy lung fibroblasts. Our previous studies have demonstrated the therapeutic potential of calcium sulfide (CaS) nanostructures in skin and breast cancer models, leading to a significant reduction in cancer cell proliferation. However, how CaS nanoclusters enhance their therapeutic effects on cancer cells while minimizing damage to healthy cells remains unknown. Our results show that CaS nanoclusters, once dissociated into ${Ca}^{2+}$ and $H_{2}S$ in an acidic microenvironment, selectively allow extracellular calcium to enter, leading to an increase in free calcium entry, triggering oxidative stress and limiting DNA repair mechanisms in NSCLC. Furthermore, CaS nanoclusters selectively arrest NSCLC cells in the G0-G1 and S phases of the cell cycle without affecting healthy cells’ cycles. Here, we also show that the selective effects of CaS nanoclusters on lung adenocarcinoma are less likely to be regulated by intrinsic apoptotic or mitochondrial pathways. They are, rather, caused by an increase in Ca²⁺ and ROS, causing double-stranded DNA breakages. This selectivity for malignant cells is pH-dependent because it occurs in the acidic microenvironment characteristic of these cells. Overall, this is the first piece of evidence that CaS disrupts genomic stability, prevents the replication of damaged cells, and ultimately influences cell fate decisions such as cell cycle arrest or cell death including mitotic catastrophe and necroptotic simultaneous events. Full article

There is a longstanding connection between “curiosity”, “desire”, and “sexuality”. This connection can be found in texts as diverse as works of scripture like the Hebrew Bible and the Quran as well as in contemporary works of critical theory. Miguel de Cervantes explored such a connection more than four centuries ago in El curioso impertinente, an exemplary novella embedded in the 1605 part one of Don Quixote. Through a comparative reading of Cervantes’s El curioso impertinent, Pedro Almodóvar’s 1997 film Carne trémula (itself a free adaptation of Ruth Rendell’s 1986 novel Live Flesh), and Luis Buñuel’s 1955 film Ensayo de un crimen, this essay analyzes the intersection of curiosity and desire—inflected through the lenses of both Girardian and Lacanian theory—in order to explore the fundamental role not just of curiosity in early modern Spain, but also in the representation of modern (and postmodern) sexuality. Full article

(1) Background: Elite sport can increase vulnerability to developing mental health pathologies. The purpose of the study is to determine the frequency at which these behavioural disorders appear in elite footballers and evaluate their relationship with other addictions. (2) Methods: A cross-sectional study was conducted between November 2020 and January 2022 on 306 participants. The variables of gambling and gaming were studied. The different groups were compared using Chi-squared tests. Probabilities exceeding 95% (p-values < 0.05) and residuals results greater than 2 or less than −2 were considered significant. (3) Results: There were significant differences between the two groups in terms of alcohol (p < 0.001), tobacco (p < 0.001), and cannabis (p = 0.016) consumption. We also found differences between those who had a history of a nervous disease (p = 0.015). 6.6% of the of football players had a probable diagnosis of a gambling disorder compared to 1% in the general population (p = 0.011). Among the pathological and non-pathological cases of gambling in the football population, significant differences were found between those with a salary of EUR 900–1500/month (p = 0.027) or a history of a nervous pathology (p = 0.021). (4) Conclusions: This study showed that professional football players were vulnerable to mental health pathologies related to gambling. Full article

The precipitation in the Mediterranean region, characterised by its annual variability and concentration in high-intensity events, is a key factor in territorial planning and the management of runoff in urban areas, particularly on the Spanish Mediterranean coast. This study focuses on the province of Alicante, applying the “daily precipitation concentration index (CI)” in 26 meteorological stations for the period 1981–2020, with the aim of analysing the statistical structure of precipitation on an annual scale. It measures the irregularity and intensity of precipitation according to the concentration of most of the annual total in a few days. Furthermore, it examines the synoptic situations and trajectories of the air masses on days of torrential rain using the HYSPLIT model. This is essential to identify the origin of moist air masses, to understand the meteorological mechanisms that intensify extreme rainfall events, and to identify recurrent patterns that explain their frequency and characteristics. The results reveal extreme CI values of between 0.58 in the interior of the province and 0.71 in the southern pre-coastal area, with a value of 0.68 in the city of Alicante. On average, the CI is 0.65, indicating that 25% of days with more rain have a concentration of around 75% of total precipitation, while 10% of the days represent 45% of the total. With respect to the origin of air masses, the most relevant in the mid-troposphere (500 hPa) are those from the north of Africa, particularly during the final periods of their trajectory, with flows from the east on the surface. Full article

Spanish film director Pedro Almodóvar has been detected early on by film critics as a Baroque filmmaker, a qualification to which he has agreed in interviews. This promotion of his style is certainly questionable as the word ‘Baroque’ is often used outside of its artistic and historical contexts. It is undeniable, however, that there are many Baroque features in his tragicomedy. One of the key aspects that ties Almodóvar’s early films to Baroque art is their exaggerated and melodramatic storytelling. Like Baroque art, which often featured grandiose and emotionally charged narratives, Almodóvar’s films are filled with intense emotions, complex relationships, and larger-than-life characters. This exaggerated portrayal of human emotions and experiences is a hallmark of Baroque aesthetics, which sought to evoke strong emotional responses from the audience. This paper seeks to focus exclusively on the rise of the director’s style in the last two decades of the 20th century that corresponds to Spain’s problematic and somewhat tragic transition from dictatorship to democracy and explore the ‘Baroque transitions’ that led Almodóvar to national, European and international recognition prior to the obtention of the Academy Awards he received for “All about my mother” in 2000. After defining the Baroqueness of his early filmography, this article will take a closer look at the ricochet trajectory he designed for actors such as Carmen Maura, Victoria Abril, and Antonio Banderas, who will all act in several corresponding roles and embody characters in transition, before becoming emblematic for the public. In the tradition of the Spanish Baroque, Almodóvar will develop his tragic outlook on his ever-changing culture around these iconic actors who will, in turn, unfold the complexity of the transition years for Spanish women and men. Full article

Background: The leading cause of blindness due to non-infectious uveitis is cystoid macular edema (CME). Behçet’s disease (BD) is one of the most commonly conditions related to CME. Objectives: To compare the effectiveness and safety of adalimumab (ADA), infliximab (IFX) and certolizumab (CZP) in refractory CME due to BD. Methods: Multicenter study of BD-CME patients with no response to glucocorticoids (GCs) and at least one conventional immunosuppressive drug. At baseline, all patients presented CME, defined by OCT > 300 µ. The effectiveness of ADA, IFX and CZP was assessed over a 2-year period from baseline using the following ocular parameters: macular thickness (µm), visual acuity (BCVA), anterior chamber (AC) cells and vitritis. Mixed-effects regression models were applied. Results: a total of 50 patients (75 eyes) were studied (ADA = 25; IFX = 15 and CZP = 10). No significant differences in demographic parameters were found among the three groups. However, individuals in the CZP group had a significantly extended time from diagnosis to treatment onset (72 (36–120) months, p = 0.03) and had received a higher number of biological therapies (1.7 ± 1.1) compared to the ADA and IFX groups. Within the CZP group, ADA and IFX were previously administrated in seven patients. After 2 years of follow-up, a rapid and sustained reduction in macular thickness was noted in all three groups with no significant differences between them. Additionally, enhancements in BCVA, AC cells and vitritis were also observed. No serious adverse events were reported in the CZP group, although one isolated case of bacteremia was documented in the ADA group. ADA, IFX and CZP appear to be effective and safe treatments for refractory CME in BD. CZP seems to remain effective even in patients with an insufficient response to ADA and/or IFX. Conclusions: ADA, IFX and CZP appear to be effective and safe treatments for refractory CME in BD. CZP seems to remain effective even in patients with an insufficient response to ADA and/or IFX. Full article