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In the context of robust Bayesian analysis, studies mainly focus on computing the range of some quantities of interest when the prior distribution varies in a class. We use the concept of distorted bands to introduce a family of priors on the shape parameter of the Generalized Pareto distribution. We show how certain properties of the likelihood ratio order allow us to propose novel sensitivity measures for Value at Risk and Conditional Value at Risk, which are the most useful and reliable risk measures. Although we focus on the Generalized Pareto distribution, which is essential in Extreme Value Theory, the new sensitivity measures could be employed for all the distributions that verify certain conditions related to likelihood ratio order. A thorough simulation study was carried out to perform a sensitivity analysis, and two illustrative examples are also provided.

Neutrophils are critical phagocytic cells in innate immunity, playing a significant role in defending against invasive fungal pathogens. This study aimed to explore the transcriptional activation of human neutrophils in response to different fungal pathogens, including Candida albicans and Aspergillus fumigatus, compared to the bacterial pathogen Escherichia coli. We identified distinct transcriptional profiles and stress-related pathways in neutrophils during fungal infections, highlighting their functional diversity and adaptability. The transcriptional response was largely redundant across all pathogens in immune-relevant categories and cytokine pathway activation. However, differences in the magnitude of differentially expressed genes (DEGs) were observed, with A. fumigatus inducing a lower transcriptional effect compared to C. albicans and E. coli. Notably, specific gene signatures associated with cell death were differentially regulated by fungal pathogens, potentially increasing neutrophil susceptibility to autophagy, pyroptosis, and neutrophil extracellular trap (NET) formation. These findings provide valuable insights into the complex immunological responses of neutrophils during fungal infections, offering new avenues for diagnostic and therapeutic strategies, particularly in the management of invasive fungal diseases.

Rhabdoid tumors (RT) are among the most aggressive tumors in early childhood. Overall survival remains poor, and treatment only effectively occurs at the cost of high toxicity and late adverse effects. It has been reported that the neurokinin-1 receptor/ substance P complex plays an important role in cancer and proved to be a promising target. However, its role in RT has not yet been described. This study aims to determine whether the neurokinin-1 receptor is expressed in RT and whether neurokinin-1 receptor (NK1R) antagonists can serve as a novel therapeutic approach in treating RTs. By in silico analysis using the cBio Cancer Genomics Portal we found that RTs highly express neurokinin-1 receptor. We confirmed these results by RT-PCR in both tumor cell lines and in human tissue samples of various affected organs. We demonstrated a growth inhibitory and apoptotic effect of aprepitant in viability assays and flow cytometry. Furthermore, this effect proved to remain when used in combination with the cytostatic cisplatin. Western blot analysis showed an upregulation of apoptotic signaling pathways in rhabdoid tumors when treated with aprepitant. Overall, our findings suggest that NK1R may be a promising target for the treatment of RT in combination with other anti-cancer therapies and can be targeted with the NK1R antagonist aprepitant.

As a recently explored agricultural practice, the controlled elicitation of plants offers high potential in multiple crop needs as growth promotion, activation of defenses and the production of specific metabolites. Extracellular DNA has been identified as a plant immune system elicitor but some aspects of the plant response have not been explored. In the present work, five DNA treatments were applied in tomato plants and the response of catalase, superoxide dismutase, phenylalanine ammonia lyase activities, hydrogen peroxide, total phenolics and flavonoid contents in leaves were spectrophotometrically measured. Treatments differed by the source and concentration of DNA and plant phenological stage of application. Furthermore, mathematical modeling and principal component analysis were performed to explore the behavior of each variable and their interaction. The most effective treatment was the self-DNA application in young plants based on the intensity and duration of immune system activation. The information given by the measured variables correlated positively with the phenylpropanoid pathway markers and negatively with catalase and superoxide dismutase activities. Results reported here propose an easy way to evaluate plant immune response activation by DNA and any other elicitor and provide useful information for future development of controlled elicitation strategies in crop production.

Drum-drying results in pregelatinized starch with relatively low starch fragmentation and a great ability to absorb water and swell at room temperature. However, the effect of the degree of cold particle swelling and the thickening potential of drum-dried starch on its suitability as oil replacer in low-fat oil-in-water emulsions has received little attention. In this work, the potential of three pregelatinized drum-dried starches with almost identical molecular structure (as measured by size exclusion chromatography) and Water Binding Capacity (WBC), but different swelling behavior, was investigated to replace up to 60% oil in a mayonnaise-like emulsion system. The microstructure, stability, and rheology of the oil-in-water emulsions were noticeably affected by the substitution of oil with a pregelatinized drum-dried starch paste. Specifically, reduced-fat emulsions presented smaller droplet-size, a higher consistency index and increased emulsion stability, especially against freeze-thaw cycles, compared to the control full-fat mayonnaise. Importantly, the differences in cold swelling behavior (rather than simply assessing WBC) greatly influenced the consistency index and stability of low-fat emulsions, and results showed that drum-dried starch particles with high swelling potential perform better as oil replacers.

While type 2 immunity has traditionally been associated with the control of parasitic infections and allergic reactions, increasing evidence suggests that type 2 immunity exerts regulatory functions on inflammatory diseases such as arthritis, and also on bone homeostasis. This review summarizes the current evidence of the regulatory role of type 2 immunity in arthritis and bone. Key type 2 cytokines, like interleukin (IL)-4 and IL-13, but also others such as IL-5, IL-9, IL-25, and IL-33, exert regulatory properties on arthritis, dampening inflammation and inducing resolution of joint swelling. Furthermore, these cytokines share anti-osteoclastogenic properties and thereby reduce bone resorption and protect bone. Cellular effectors of this action are both T cells (i.e., Th2 and Th9 cells), but also non-T cells, like type 2 innate lymphoid cells (ILC2). Key regulatory actions mediated by type 2 cytokines and immune cells on both inflammation as well as bone homeostasis are discussed.

A Bayesian hierarchical framework with a Gaussian copula and a generalized extreme value (GEV) marginal distribution is proposed for the description of spatial dependencies in data. This spatial copula model was applied to extreme summer temperatures over the Extremadura Region, in the southwest of Spain, during the period 1980–2015, and compared with the spatial noncopula model. The Bayesian hierarchical model was implemented with a Monte Carlo Markov Chain (MCMC) method that allows the distribution of the model’s parameters to be estimated. The results show the GEV distribution’s shape parameter to take constant negative values, the location parameter to be altitude dependent, and the scale parameter values to be concentrated around the same value throughout the region. Further, the spatial copula model chosen presents lower deviance information criterion (DIC) values when spatial distributions are assumed for the GEV distribution’s location and scale parameters than when the scale parameter is taken to be constant over the region.

Short-chain fatty acids are gut-bacteria-derived metabolites that execute important regulatory functions on adaptive immune responses, yet their influence on inflammation driven by innate immunity remains understudied. Here, we show that propionate treatment in drinking water or upon local application into the joint reduced experimental arthritis and lowered inflammatory tissue priming mediated by synovial fibroblasts. On a cellular level, incubation of synovial fibroblasts with propionate or a physiological mixture of short-chain fatty acids interfered with production of inflammatory mediators and migration and induced immune-regulatory fibroblast senescence. Our study suggests that propionate mediates its alleviating effect on arthritis by direct abrogation of local arthritogenic fibroblast function.

Benefits and harms of different components of human diet have been known for hundreds of years. Alcohol is one the highest consumed, abused, and addictive substances worldwide. Consequences of alcohol abuse are increased risks for diseases of the cardiovascular system, liver, and nervous system, as well as reduced immune system function. Paradoxically, alcohol has also been a consistent protective factor against the development of autoimmune diseases such as type 1 diabetes, multiple sclerosis, systemic lupus erythematosus, and rheumatoid arthritis (RA). Here, we focused on summarizing current findings on the effects of alcohol, as well as of its metabolites, acetaldehyde and acetate, on the immune system and RA. Heavy or moderate alcohol consumption can affect intestinal barrier integrity, as well as the microbiome, possibly contributing to RA. Additionally, systemic increase in acetate negatively affects humoral immune response, diminishing TFH cell as well as professional antigen-presenting cell (APC) function. Hence, alcohol consumption has profound effects on the efficacy of vaccinations, but also elicits protection against autoimmune diseases. The mechanism of alcohol’s negative effects on the immune system is multivariate. Future studies addressing alcohol and its metabolite acetate’s effect on individual components of the immune system remains crucial for our understanding and development of novel therapeutic pathways.

The interaction and crosstalk of Toll-like receptors (TLRs) is an established pathway in which the innate immune system recognises and fights pathogens. In a single nucleotide polymorphisms (SNP) analysis of an Indian cohort, we found evidence for both TLR4-399T and TRL8-1A conveying increased susceptibility towards tuberculosis (TB) in an interdependent manner, even though there is no established TLR4 ligand present in Mycobacterium tuberculosis (Mtb), which is the causative pathogen of TB. Docking studies revealed that TLR4 and TLR8 can build a heterodimer, allowing interaction with TLR8 ligands. The conformational change of TLR4-399T might impair this interaction. With immunoprecipitation and mass spectrometry, we precipitated TLR4 with TLR8-targeted antibodies, indicating heterodimerisation. Confocal microscopy confirmed a high co-localisation frequency of TLR4 and TLR8 that further increased upon TLR8 stimulation. The heterodimerisation of TLR4 and TLR8 led to an induction of IL12p40, NF-κB, and IRF3. TLR4-399T in interaction with TLR8 induced an increased NF-κB response as compared to TLR4-399C, which was potentially caused by an alteration of subsequent immunological pathways involving type I IFNs. In summary, we present evidence that the heterodimerisation of TLR4 and TLR8 at the endosome is involved in Mtb recognition via TLR8 ligands, such as microbial RNA, which induces a Th1 response. These findings may lead to novel targets for therapeutic interventions and vaccine development regarding TB.

This study provides fundamental insight and offers a promising catalytic hydrothermal method to harness cranberry pomace as a potential bioenergy and/or hydrochar source. The physical and chemical properties of Canadian cranberry pomace, supplied by Fruit d’Or Inc., were examined and the optimum operational conditions, in terms of biocrude yield, were obtained by the I-optimal matrix of Design Expert 11. Afterward, cranberry pomace hydrochar (CPH) and zeolite were separately introduced to the hydrothermal liquefaction (HTL) process to investigate the benefits and disadvantages associated with their catalytic activity. CPH was found to be a better host than zeolite to accommodate cellulosic sugars and showed great catalytic performance in producing hydrocarbons. However, high amounts of corrosive amino and aliphatic acids hinder the practical application of CPH as a catalyst. Alternatively, zeolite, as a commercial high surface area catalyst, had a higher activity for deoxygenation of compounds containing carbonyl, carboxyl, and hydroxyl groups than CPH and resulted in higher selectivity of phenols. Due to the low hydrothermal structural stability, coke formation, and narrow pore size distribution, further activations and modifications are needed to improve the catalytic behavior of zeolite. Our results suggest that a composite composed of CPH and zeolite can resolve the abovementioned limitations and help with the development and commercialization of advanced biofuels from cranberry pomace.

Chronic inflammatory diseases are often initiated and guided by the release of proinflammatory mediators. Rheumatoid arthritis (RA) is caused by an imbalance between the pro- and anti-inflammatory mediators in the joints, thereby favoring chronic inflammation and joint damage. Here, we investigate if short-term high-fiber dietary intervention shifts this towards anti-inflammatory mediators. Healthy controls (n = 10) and RA patients (n = 29) under routine care received daily high-fiber bars for 15 or 30 days, respectively. Stool and sera were analyzed for pro- and anti-inflammatory mediators. A high-fiber dietary intervention resulted in increased anti-inflammatory short-chain fatty acids (SCFA), decreased proarthritic cytokine concentrations, along with a durable shift in the Firmicutes-to-Bacteroidetes ratio. Together, these results further strengthen high-fiber dietary interventions as a practical approach complementing existing pharmacological therapies.

The objective was to modify functional properties of breadfruit flours using twin-screw extrusion and test the physicochemical properties of the extruded flours. Extruded breadfruit flours were produced with twin-screw extrusion using different last barrel temperature (80 °C or 120 °C) and feed moisture content (17% or 30%). These conditions resulted in four extruded flours with different mechanical (specific mechanical energy, SME) and thermal (melt temperature) energies. At temperatures below the gelatinization of the native starch (

The pasting profile of starchy tissues is conventionally measured by recording the apparent viscosity (η) in heating/cooling cycles. However, conventional rheometers show critical limitations when the starch is embedded in compact protein-rich cotyledon matrices, as occurs in pulses. In this work, the pasting profile of 13 red kidney beans (Phaseolus vulgaris) from the same cultivar but different growing locations was investigated using a heating/cooling cycle at higher temperature (130 °C) and pressurized conditions, using both water and brine as cooking solvents. It was hypothesized that the continuous measure of η at these conditions of flours from the dry seed would correlate with the texture, as determined by the mini-Kramer cell, of the beans after the entire process of soaking and canning. Furthermore, mechanistic answers were obtained by investigating their composition (starch, protein, and ash content) and physical properties (water holding capacity, seed ratio and weight). Interestingly, as opposed to the pasting profile at 95 °C, pasting indicators at 130 °C, including trough and final viscosity, strongly correlated with starch and protein content, seed coat ratio and, remarkably, with the firmness of the beans after canning when brine was incorporated. These results clearly show that small beans with a high protein content would bring about a more compact matrix that restricts starch from swelling and results in canned beans with a hard texture, which can be predicted by a lower pasting profile of the whole bean flour.

Aerial Thermal Infrared (TIR) imagery has demonstrated tremendous potential to monitor active forest fires and acquire detailed information about fire behavior. However, aerial video is usually unstable and requires inter-frame registration before further processing. Measurement of image misalignment is an essential operation for video stabilization. Misalignment can usually be estimated through image similarity, although image similarity metrics are also sensitive to other factors such as changes in the scene and lighting conditions. Therefore, this article presents a thorough analysis of image similarity measurement techniques useful for inter-frame registration in wildfire thermal video. Image similarity metrics most commonly and successfully employed in other fields were surveyed, adapted, benchmarked and compared. We investigated their response to different camera movement components as well as recording frequency and natural variations in fire, background and ambient conditions. The study was conducted in real video from six fire experimental scenarios, ranging from laboratory tests to large-scale controlled burns. Both Global and Local Sensitivity Analyses (GSA and LSA, respectively) were performed using state-of-the-art techniques. Based on the obtained results, two different similarity metrics are proposed to satisfy two different needs. A normalized version of Mutual Information is recommended as cost function during registration, whereas 2D correlation performed the best as quality control metric after registration. These results provide a sound basis for image alignment measurement and open the door to further developments in image registration, motion estimation and video stabilization for aerial monitoring of active wildland fires.

The objective of this study was to compare the compositional and functional properties of tropical flour sources (two breadfruit flours (type A and type B) and a banana flour) with a more traditional flour source (wheat flour). Macro-nutrient composition, pH, water and oil holding capacity, bulk density, particle size, solubility, swelling power, pasting properties, and thermodynamics (gelatinization and retrogradation) were determined. All flours evaluated were similar in their composition with high levels of carbohydrates (greater than 82.52 g/100 g on a dry-matter basis), with most of the carbohydrate content comprised of starch (greater than 67.02 g/100 g). The tropical fruit flours had greater (p < 0.05) water holding capacity than wheat flour. Breadfruit flour B had the lowest (p < 0.05) bulk density, while banana flour had the greatest (p < 0.05) bulk density. The swelling power of the tropical flours was greater (p < 0.05) than the wheat flour. The viscosity of the tropical flours was higher than wheat flour but decreased significantly when temperature was held at 130 °C. These results indicated that the two breadfruit flours and banana flour have great potential for application in processed food products, and have similar compositional attributes to a more traditional flour.

Short-chain fatty acids are microbial metabolites that have been shown to be key regulators of the gut−joint axis in animal models. In humans, microbial dysbiosis was observed in rheumatoid arthritis (RA) patients as well as in those at-risk to develop RA, and is thought to be an environmental trigger for the development of clinical disease. At the same time, diet has a proven impact on maintaining intestinal microbial homeostasis. Given this association, we performed a feasibility study in RA patients using high-fiber dietary supplementation with the objective to restore microbial homeostasis and promote the secretion of beneficial immunomodulatory microbial metabolites. RA patients (n = 36) under routine care received daily high-fiber bars or cereals for 28 days. Clinical assessments and laboratory analysis of immune parameters in blood and stool samples from RA patients were done before and after the high-fiber dietary supplementation. We observed an increase in circulating regulatory T cell numbers, favorable Th1/Th17 ratios, as well as decreased markers of bone erosion in RA patients after 28 days of dietary intervention. Furthermore, patient-related outcomes of RA improved. Based on these results, we conclude that controlled clinical studies of high-fiber dietary interventions could be a viable approach to supplement or complement current pharmacological treatment strategies.

The term “baked goods” encompasses multiple food products made from flour (typically wheat flour) [...]

Bread is categorized as having a high amount of rapidly digested starch that may result in a rapid increase in postprandial blood glucose and, therefore, poor health outcomes. This is mostly the result of the complete gelatinization that starch undergoes during baking. The inclusion of resistant starch (RS) ingredients in bread formulas is gaining prominence, especially with the current positive health outcomes attributed to RS and the apparition of novel RS ingredients in the market. However, many RS ingredients contain RS structures that do not resist baking and, therefore, are not suitable to result in a meaningful RS increase in the final product. In this review, the structural factors for the resistance to digestion and hydrothermal processing of RS ingredients are reviewed, and the definition of each RS subtype is expanded to account for novel non-digestible structures recently reported. Moreover, the current in vitro digestion methods used to measure RS content are critically discussed with a view of highlighting the importance of having a harmonized method to determine the optimum RS type and inclusion levels for bread-making.

Hydrogen peroxide (H2O2) is an important ROS molecule (Reactive oxygen species) that serves as a signal of oxidative stress and activation of signaling cascades as a result of the early response of the plant to biotic stress. This response can also be generated with the application of elicitors, stable molecules that induce the activation of transduction cascades and hormonal pathways, which trigger induced resistance to environmental stress. In this work, we evaluated the endogenous H2O2 production caused by salicylic acid (SA), chitosan (QN), and H2O2 elicitors in Capsicum annuum L. Hydrogen peroxide production after elicitation, catalase (CAT) and phenylalanine ammonia lyase (PAL) activities, as well as gene expression analysis of cat1, pal, and pathogenesis-related protein 1 (pr1) were determined. Our results displayed that 6.7 and 10 mM SA concentrations, and, 14 and 18 mM H2O2 concentrations, induced an endogenous H2O2 and gene expression. QN treatments induced the same responses in lesser proportion than the other two elicitors. Endogenous H2O2 production monitored during several days, showed results that could be an indicator for determining application opportunity uses in agriculture for maintaining plant alert systems against a stress.

A germin-like gene (CchGLP) cloned from geminivirus-resistant pepper (Capsicum chinense Jacq. Line BG-3821) was characterized and the enzymatic activity of the expressed protein analyzed. The predicted protein consists of 203 amino acids, similar to other germin-like proteins. A highly conserved cupin domain and typical germin boxes, one of them containing three histidines and one glutamate, are also present in CchGLP. A signal peptide was predicted in the first 18 N-terminal amino acids, as well as one putative N-glycosylation site from residues 44–47. CchGLP was expressed in E. coli and the recombinant protein displayed manganese superoxide dismutase (Mn-SOD) activity. Molecular analysis showed that CchGLP is present in one copy in the C. chinense Jacq. genome and was induced in plants by ethylene (Et) and salicylic acid (SA) but not jasmonic acid (JA) applications in the absence of pathogens. Meanwhile, incompatible interactions with either Pepper golden mosaic virus (PepGMV) or Pepper huasteco yellow vein virus (PHYVV) caused local and systemic CchGLP induction in these geminivirus-resistant plants, but not in a susceptible accession. Compatible interactions with PHYVV, PepGMV and oomycete Phytophthora capsici did not induce CchGLP expression. Thus, these results indicate that CchGLP encodes a Mn-SOD, which is induced in the C. chinense geminivirus-resistant line BG-3821, likely using SA and Et signaling pathways during incompatible interactions with geminiviruses PepGMV and PHYVV.

Aptamers are single-stranded oligonucleotides (ssDNA or ssRNA) that bind and recognize their targets with high affinity and specificity due to their complex tertiary structure. Aptamers are selected by a method called SELEX (Systematic Evolution of Ligands by EXponential enrichment). This method has allowed the selection of aptamers to different types of molecules. Since then, many aptamers have been described for the potential treatment of several diseases including cancer. It has been described over the last few years that aptamers represent a very useful tool as therapeutics, especially for cancer therapy. Aptamers, thanks to their intrinsic oligonucleotide nature, present inherent advantages over other molecules, such as cell-based products. Owing to their higher tissue penetrability, safer profile, and targeting capacity, aptamers are likely to become a novel platform for the delivery of many different types of therapeutic cargos. Here we focus the review on interfering RNAs (iRNAs) as aptamer-based targeting delivered agents. We have gathered the most reliable information on aptamers as targeting and carrier agents for the specific delivery of siRNAs, shRNA, microRNAs, and antisense oligonucleotides (ASOs) published in the last few years in the context of cancer therapy.

The first documented case of melioidosis in the Philippines occurred in 1948. Since then, there have been sporadic reports in the literature about travelers diagnosed with melioidosis after returning from the Philippines. Indigenous cases, however, have been documented rarely, and under-reporting is highly likely. This review collated all Philippine cases of melioidosis published internationally and locally, as well as unpublished case series and reports from different tertiary hospitals in the Philippines. In total, 25 papers and 41 cases were identified. Among these, 23 were indigenous cases (of which 20 have not been previously reported in the literature). The most common co-morbidity present was diabetes mellitus, and the most common presentations were pulmonary and soft tissue infections. Most of the cases received ceftazidime during the intensive phase, while trimethoprim-sulfamethoxazole was given during the eradication phase. The known mortality rate was 14.6%, while 4.9% of all cases were reported to have had recurrence. The true burden of melioidosis in the country is not well defined. A lack of awareness among clinicians, a dearth of adequate laboratories, and the absence of a surveillance system for the disease are major challenges in determining the magnitude of the problem.

Introduction: Adherence to mesalamine therapy in ulcerative colitis is often inadequate. This affects long-term remission and to some extent the risk of colon cancer. Means for assessing non-adherent behavior are cumbersome, expensive, and/or time consuming. Unless multiple tools are used in association, a proportion of patients with volitional and non-volitional non-adherence is nonetheless undetected. The study was aimed at evaluating to which extent rephrasing a single question on adherence to mesalamine therapy may help identifying patients who are not compliant with medication prescription. Methods: One-hundred and seventy-four inflammatory bowel disease outpatients were asked in two consecutive visits, in random order, if they “regularly assumed the prescribed dose of mesalamine” (adherence-centered question—AQ) or “how often they skipped mesalamine pills” (non-adherence centered question—NQ). Answer concordance was evaluated in relation to clinical and demographic variables. Results: The concordance between AQ and NQ was low (K = 0.22). Lower compliance to therapy was admitted in 37.4% more patients following NQ than AQ. The reported adherence to AQ was invariably higher than that of NQ, irrespective of the variable taken into consideration. The likelihood of non-concordant answers was non-significantly higher in CD patients than in UC and in patients with shorter disease duration than in those with longstanding disease, but the logistic regression model did not identify individual variables responsible for the different answers. Conclusions: Being simple and not requiring additional time expense, centering the question on medication non-adherence identifies a large proportion of patients who would not admit non-adherence or underestimate the number of skipped doses of medication, when directly asked if they are compliant to therapy.

District heating and cooling networks represent a compelling energy system solution due to their capacity to integrate renewable energies and leverage local surpluses of thermal resources. The meticulous design and optimization of network infrastructure are imperative to fully exploiting the potential of these energy systems. The Life Cycle Assessment of district heating and cooling networks for the purpose of environmental sustainability is a crucial and increasingly demanded aspect, particularly in light of the progressively stringent European regulations. The Life Cycle Assessment methodology could offer an evaluation throughout the entire life cycle of such networks. The proposed review scrutinizes the application of the Life Cycle Assessment methodology to evaluating the environmental profile of district heating and cooling systems. The methods, findings, and challenges are examined through a literature review and case study analysis. The results highlight variations in the climate profile influenced by the network generation type and multifunctionality approaches. The analysis revealed a range of emission factors, spanning from 11 gCO2eq/kWhth to 470 gCO2eq/kWhth for district heating and 6 gCO2eq/kWhth to 64 gCO2eq/kWhth for district cooling. The discussion emphasizes integrating district heating and cooling network management considerations and addressing methodological challenges. This study concludes by proposing future research directions for developing a universal LCA-based tool for district heating and cooling network analysis.

Pilgrimage tourism, among the earliest forms of tourism with a tradition spanning centuries, stands as a steadfast global attraction. This article delves into the significance, diversity, and historical roots of this tourism type, recognizing the contemporary surge in interest in pilgrimage sites. Offering an overview of globally prominent pilgrimage destinations and highlighting key locations in Slovakia, the article emphasizes the country’s considerable potential for the utilization and development of these sacred sites, despite its compact size. It stresses the need to foster this historically significant tourism sector and the necessity for attention and support from the government sector to maximize its potential. The relevance of pilgrimage became particularly apparent during the COVID-19 pandemic, with observable visitor participation despite challenging conditions at various pilgrimage sites. The article examines the pilgrimage’s evolution before, during, and after the pandemic, using Levoča and Šaštín in Slovakia as illustrative cases. One of the main objectives of this study was to clarify the development of pilgrimage tourism in Slovakia over the past decades and the factors influencing it. The attendance analysis unmistakably reveals a significant upward trend at these specific locations, emphasizing the need to establish collaborative efforts to support this sector. Such collaboration is crucial for ensuring the sustainability of historically significant sites, fostering local development, and increasing the visibility of less-visited pilgrimage destinations.

Background and Objectives: Atrial fibrillation (AF) is increasingly recognised in paediatric patients, presenting unique challenges in management due to its association with various underlying heart conditions. This study aimed to evaluate the prevalence, management strategies, and outcomes of AF in this population. Materials and Methods: A retrospective analysis was conducted at a tertiary paediatric cardiology centre, including patients aged ≤18 years diagnosed with AF between January 2015 and December 2023. The study focused on demographic details, clinical presentations, treatments, and outcomes. Descriptive statistics were employed to assess treatment efficacy, recurrence rates, and complications. Results: The study included 36 paediatric patients (median age: 15 years, IQR: 13–17; 58% male). Of these, 52.8% had acquired heart disease, 16.7% had congenital heart anomalies, and 16.7% presented with lone AF. The initial management strategies involved electrical cardioversion in 53.3% of patients and pharmacological conversion with amiodarone in 46.7%. Rhythm control therapy was administered to over 80% of the cohort, and 63.9% were placed on oral anticoagulation, predominantly for rheumatic and congenital heart diseases. The overall success rate of rhythm control was 96.2%, with an AF recurrence rate of 3.8%. Ischemic stroke was the most common complication, occurring in three patients, all with underlying rheumatic heart disease. Conclusions: AF in paediatric patients is predominantly associated with rheumatic and congenital heart diseases, though a significant proportion of patients present with lone AF. Despite effective rhythm control in most cases, neurological complications, particularly ischemic strokes in patients with underlying heart disease, remain a critical concern. These findings underscore the need for more comprehensive studies to better understand the aetiology, risk factors, and optimal management strategies for paediatric AF.

Monitoring atmospheric pollution in urban areas is challenging because pollutant deposition occurs at short distances, requiring a large amount of sampling and analysis to characterize it. Ecological indicators can help overcome this problem, allowing us to select sites with the highest deposition of pollutants from the atmosphere. Nevertheless, a major gap is the temporal characterization of the accumulation rate of magnetic particles in ecological indicators, which is critical to understand if the bioaccumulation process is linear or if saturation occurs. To overcome this problem, Parmotrema perlatum lichens were magnetically and chemically studied in a pollution gradient over space and time. Lichen transplants were exposed over 18 weeks to a high-traffic road. Results show that magnetic properties and element composition reflected both distance from the road (nonlinear decrease of up to 100 m from source) and exposure time (increasingly linearly over the entire study period with eightfold increments), showing that up to 18 weeks, the accumulation rate remained constant over time, with no saturation occurring. Chemical analysis showed a strong linear relationship between the accumulation of zinc (Zn), antimony (Sb), manganese (Mn), copper (Cu) chromium (Cr) and magnetic susceptibility. Magnetization acquisition curves reveal a time-dependent low-coercivity component, interpreted as mainly related to nonexhaust, mostly brake abrasion particle emissions. It is concluded that the magnetic properties of lichen transplants can be used in urban environments to characterize the spatial and temporal patterns of the deposition of pollution metallic particles from the atmosphere.

Background: Managing pain and distress in children experiencing procedural pain is a priority in pediatric care. Nitrous oxide (pre-mixed formulation of 50% nitrous oxide to 50% oxygen) is widely used to alleviate anxiety or pain during care procedures in various medical domains. This pharmacological intervention is safe to administer to children. Administration by non-anesthesiologist personnel is widespread throughout the world, though it is almost exclusively performed by doctors and nurses. The purpose of this study is to describe the experience of nitrous oxide (N2O) use by medical assistants and safe handling during the performance of painful procedures. Methods: A retrospective study was conducted in a pediatric outpatient unit of a regional hospital, including medical and surgical consultations. Results: Nitrous oxide was administered by medical assistants to 324 children aged 3 to 19 years. No respiratory and/or cardiovascular problems were noted. Most patients were calm and relaxed. Discussion: The use of N2O for minor procedures in children in a pediatric outpatient unit improved pain management through administration by medical assistants with a high level of satisfaction from patients, parents and health professionals. Conclusions: This study suggests that the use of nitrous oxide by trained medical assistants can be safe, feasible and effective within the specific context of this study.

Several technologies have been introduced into neurorehabilitation programs to enhance traditional treatment of individuals with Spinal Cord Injury (SCI). Their effectiveness has been widely investigated, but their adoption has not been properly quantified. The aim of this study is to assess the distribution of conventional (Treatment As Usual—TAU) and technology-aided (Treatment With Technologies—TWT) treatments conveniently grouped based on different therapeutic goals in a selected SCI unit. Data from 104 individuals collected in 29 months were collected in a custom database and categorized according to both the conventional American Impairment Scale classification and a newly developed Multifactor (MF) clustering approach that considers additional sources of information (the lesion level, the level of independence in the activities of daily living, and the hospitalization duration). Results indicated an average technology adoption of about 30%. Moreover, the MF clusters were less overlapped, and the differences in TWT adoption were more pronounced than in AIS-based clustering. MF clustering was capable of grouping individuals based both on neurological features and functional abilities. In particular, individuals with motor complete injuries were grouped together, whereas individuals with sensorimotor incomplete SCI were collected separately based on the lesion level. As regards TWT adoption, we found that in the case of motor complete SCI, TWT for muscle tone control and modulation was mainly selected (about 90% of TWT), while the other types of TWT were seldom adopted. Even for individuals with incomplete SCI, the most frequent rehabilitation goal was muscle tone modulation (about 75% of TWT), regardless of the AIS level, and technologies to improve walking ability (about 12% of TWT) and balance control (about 10% of TWT) were mainly used for individuals with thoracic or lumbar lesions. Analyzing TAU distribution, we found that the highest adoption of muscle tone modulation strategies was reported in the case of individuals with motor complete SCI (about 42% of TAU), that is, in cases when almost no gait training was pursued (about 1% of TAU). In the case of cervical motor incomplete SCI, compared to thoracic and lumbar incomplete SCI, there was a greater focus on muscle tone control and force recruitment in addition to walking training (38% and 14% of TAU, respectively) than on balance training. Overall, the MF clustering provided more insights than the traditional AIS-based classification, highlighting differences in TWT adoption. These findings suggest that a wider overview that considers both neurological and functional characteristics of individuals after SCI based on a multifactor analysis could enhance the personalization of neurorehabilitation strategies.

Fuel consumption, fuel cost savings, environmental pollution, and navigation safety are significant factors for shipping companies. Maritime transport represents 3% of total greenhouse gas emissions globally. Trim optimization is one of the ways to save energy and reduce ship emissions. Thus, this study aimed to evaluate how the optimization of the trim of container ships at different speeds can decrease exhaust gas emissions and fuel consumption while considering the safety of navigation. This research was conducted by calculating the fuel consumption in real conditions and calculating the optimal trim for different speeds and gases of a container ship of 11,400 TEU. All obtained results were statistically processed to analyze fuel consumption at various speeds, considering the ship’s trim. It turns out that savings should never be at the expense of navigation safety, especially in limited maneuvering areas, such as canals. When maneuvering in such places it is necessary to adjust the trim to ensure navigation safety, i.e., to improve the rudder and propulsion device response, instead of reducing fuel consumption

This study presents a detailed case analysis of a 40-year-old male patient with hemophilia A and severe chronic elbow arthropathy, exploring the surgical challenges and outcomes within the context of the current literature. The patient, with a history of multiple comorbidities including Hodgkin’s lymphoma and cardiomyopathy, exhibited significant joint damage and functional impairment. A comprehensive approach was employed, collecting all relevant clinical data, including radiographic and MRI findings, to inform treatment decisions. Clinical findings and treatment decisions are presented as they occurred in real time, simulating the clinical reasoning process. Subsequent references to the clinical and instrumental findings as well therapeutic interventions are discussed in light of the current literature to reinforce the decision-making framework. This report underscores the importance of multidisciplinary care in optimizing patient outcomes and contributes to the ongoing discourse on the management of advanced musculoskeletal conditions in hemophilic patients. The findings emphasize the necessity for early intervention and specialized care to mitigate complications and improve long-term prognosis.

Occupational accidents are a serious public health issue. In this retrospective observational study, we examined all injuries involving healthcare workers of the Abruzzo Local Health Authority No. 1 (Italy) during the three years 2019–2021. Data were collected by tracing the injury reports filed by the emergency service during the workers’ admission and analyzing the cause, type, distribution by sex, and geographical district to which they belonged, taking into account the period before and during the COVID-19 pandemic outbreak. Most injuries (45.7%) were reported in the Marsica area; the most common cause was commuting accidents (10.7%). Assaults were more common among men (8.6%), while commuting accidents were more common among women (11.8%). In 36% of cases, the upper limbs were affected. The most common type of injury was contusions (22.2%). When the frequency of reports was compared between the pre-pandemic and pandemic periods, there was an increase in injuries in healthcare assistants (p = 0.052), while the percentage of injuries in administrative (p = 0.056) and other categories decreased (p = 0.002). This analysis allows us to identify points of interest relating to the Marsica area, to specific types of accidents, such as aggression and commuting accidents, and to specific duties.

Introduction: Osteoarthritis is a degenerative condition of the cartilage, often common among the population and occurs frequently with aging. Many factors are decisive for the development of its pathogenesis such as age, obesity, trauma, mechanical load, and modification of synovial biology. The main features of osteoarthritis are chondrocytes and cartilage matrix loss, which lead to pain, loss of function of the whole joint, and disability, representing a relevant health problem. Recently, a new therapeutic approach based on cell therapy has been studying the regenerative ability of mesenchymal stem cells for osteoarthritic chondrocytes. Aim: This in vitro study clarifies the regenerative effects of multipotent adipose-derived stem cells and the pluripotent amniotic epithelial stem cells on arthrosis chondrocytes by performing co-culture experiments. Methods: We studied the regenerative potential of secretome (soluble factors and extracellular vesicles), mesenchymal stem cells, and the adipose stromal vascular fraction. The regenerative effects were evaluated by gene and protein expression analysis of articular cartilage-specific genes and proteins like col2a1, acan, and sox9. Results: Mesenchymal stem cells, secretome, and adipose stromal vascular fractions influenced the cartilage genes and protein expression. Conclusions: The results indicate that the treatment with mesenchymal stem cells could be the best biological approach for cartilage regenerative medicine.

Resistance biomarkers are needed to identify patients with advanced melanoma obtaining a response to ICI treatment and developing resistance later. We searched a combination of molecular signatures of response to ICIs in patients with metastatic melanoma. In a retrospective study on patients with metastatic melanoma treated with an anti-PD-1 agent carried out at Istituto Nazionale Tumori—IRCCS—Fondazione “G. Pascale”, Naples, Italy. We integrated a whole proteome profiling of metastatic tissue with targeted transcriptomics. To assess the prognosis of patients according to groups of low and high risk, we used PFS and OS as outcomes. To identify the proteins and mRNAs gene signatures associated with the patient’s response groups, the discriminant analysis for sparse data performed via partial least squares procedure was performed. Tissue samples from 22 patients were analyzed. A combined protein and gene signature associated with poorer response to ICI immunotherapy in terms of PFS and OS was identified. The PFS and OS Kaplan–Meier curves were significantly better for patients with high expression of the protein signature compared to patients with low expression of the protein signature and who were high-risk (Protein: HR = 0.023, 95% CI: 0.003–0.213; p < 0.0001. Gene: HR = 0.053, 95% CI: 0.011–0.260; p < 0.0001). The Kaplan–Meier curves showed that patients with low-risk gene signatures had better PFS (HR = 0 0.221, 95% CI: 0.071–0.68; p = 0.007) and OS (HR = 0.186, 95% CI: 0.05–0.695; p = 0.005). The proteomic and transcriptomic combined analysis was significantly associated with the outcomes of the anti-PD-1 treatment with a better predictive value compared to a single signature. All the patients with low expression of protein and gene signatures had progression within 6 months of treatment (median PFS = 3 months, 95% CI: 2–3), with a significant difference vs. the low-risk group (median PFS = not reached; p < 0.0001), and significantly poorer survival (OS = 9 months, 95% CI: 5–9) compared to patients with high expression of protein and gene signatures (median OS = not reached; p < 0.0001). We propose a combined proteomic and transcriptomic signature, including genes involved in pro-tumorigenic pathways, thereby identifying patients with reduced probability of response to immunotherapy with ICIs for metastatic melanoma.

Amelogenesis imperfecta (AI) is a genetic disease characterized by poor formation of tooth enamel. AI occurs due to mutations, especially in AMEL, ENAM, KLK4, MMP20, and FAM83H, associated with changes in matrix proteins, matrix proteases, cell-matrix adhesion proteins, and transport proteins of enamel. Due to the wide variety of phenotypes, the diagnosis of AI is complex, requiring a genetic test to characterize it better. Thus, there is a demand for developing low-cost, noninvasive, and accurate platforms for AI diagnostics. This case-control pilot study aimed to test salivary vibrational modes obtained in attenuated total reflection fourier-transformed infrared (ATR-FTIR) together with machine learning algorithms: linear discriminant analysis (LDA), random forest, and support vector machine (SVM) could be used to discriminate AI from control subjects due to changes in salivary components. The best-performing SVM algorithm discriminates AI better than matched-control subjects with a sensitivity of 100%, specificity of 79%, and accuracy of 88%. The five main vibrational modes with higher feature importance in the Shapley Additive Explanations (SHAP) were 1010 cm−1, 1013 cm−1, 1002 cm−1, 1004 cm−1, and 1011 cm−1 in these best-performing SVM algorithms, suggesting these vibrational modes as a pre-validated salivary infrared spectral area as a potential biomarker for AI screening. In summary, ATR-FTIR spectroscopy and machine learning algorithms can be used on saliva samples to discriminate AI and are further explored as a screening tool.

The metabolites secreted by probiotics or released after their lysis are called postbiotics. They provide physiological benefits to the host, preventing the colonisation of pathogens by improving the intestinal environment for beneficial commensal bacteria, which reduces the incidence of digestive disorders and improves the immune system. The aim of this work was to evaluate the addition of postbiotics to dairy cow rations during the transition period on nutrient digestibility, composition, and milk yield. The effects of two postbiotics were evaluated in twelve Friesian cows from 30 days before calving to two months of lactation. The animals were randomly allocated to two treatment groups: control (CT) and supplemented with postbiotics (PC and PR). Feeding was ad libitum with 60/40 of forage/concentrate ratio on dry matter basis. Daily feed intake and milk production were recorded individually throughout the study. Two digestibility balances were performed, one before parturition and one after parturition. Colostrum was sampled at first milking and milk was sampled weekly. Data were analysed using a mixed mode in R software 4.4.1. The results suggest that postbiotic supplementation in late gestation and early lactation increase the voluntary intake of dry matter, especially in the PR treatment, with higher apparent total tract digestibility of dry matter, organic matter and neutral detergent fibre. Both treatments including postbiotics induced an increase in colostral immunoglobulin concentration. Milk production of cows receiving the PC treatment was the highest, with high fat and protein yields and a higher persistence of the production curve throughout the lactation.

Transfer RNA (tRNA) modifications are essential for the temperature adaptation of thermophilic and psychrophilic organisms as they control the rigidity and flexibility of transcripts. To further understand how specific tRNA modifications are adjusted to maintain functionality in response to temperature fluctuations, we investigated whether tRNA modifications represent an adaptation of bacteria to different growth temperatures (minimal, optimal, and maximal), focusing on closely related psychrophilic (P. halocryophilus and E. sibiricum), mesophilic (B. subtilis), and thermophilic (G. stearothermophilus) Bacillales. Utilizing an RNA sequencing approach combined with chemical pre-treatment of tRNA samples, we systematically profiled dihydrouridine (D), 4-thiouridine (s4U), 7-methyl-guanosine (m7G), and pseudouridine (Ψ) modifications at single-nucleotide resolution. Despite their close relationship, each bacterium exhibited a unique tRNA modification profile. Our findings revealed increased tRNA modifications in the thermophilic bacterium at its optimal growth temperature, particularly showing elevated levels of s4U8 and Ψ55 modifications compared to non-thermophilic bacteria, indicating a temperature-dependent regulation that may contribute to thermotolerance. Furthermore, we observed higher levels of D modifications in psychrophilic and mesophilic bacteria, indicating an adaptive strategy for cold environments by enhancing local flexibility in tRNAs. Our method demonstrated high effectiveness in identifying tRNA modifications compared to an established tool, highlighting its potential for precise tRNA profiling studies.

The evaluation of the left atrial (LA) size using the LA volume index (LAVI) is clinically relevant due to its prognostic significance in various conditions. Nonetheless, adding a LA function assessment to the LAVI provides further clinical and prognostic information in different cardiovascular (CV) diseases. The assessment of LA function by echocardiography primarily includes volumetric measurements (LA ejection fraction [LAEF]), tissue Doppler imaging (TDI) (mitral annular late diastolic velocity [a’]), and speckle-tracking methods, such as LA longitudinal reservoir strain (LA strain). This review analyzes and discusses the current medical evidence and potential clinical usefulness of these different methods to analyze LA function.