Pathogens such as bacteria, fungi and viruses are important components of soil and aquatic communities, where they can benefit from decaying and living organic matter, and may opportunistically infect human and animal hosts. One-third of human infectious diseases is constituted by sapronotic disease agents that are natural inhabitants of soil or aquatic ecosystems. They are capable of existing and reproducing in the environment outside of the host for extended periods of time. However, as ecological research on sapronosis is infrequent and epidemiological models are even rarer, very little information is currently available. Their importance is overlooked in medical and veterinary research, as well as the relationships between free environmental forms and those that are pathogenic. Here, using dynamical models in realistic aquatic metacommunity systems, we analyze sapronosis transmission, using the human pathogen Mycobacterium ulcerans that is responsible for Buruli ulcer. Our work constitutes the first set of metacommunity models of sapronotic disease transmission, and is highly flexible for adaptation to other types of sapronosis. The importance of sapronotic agents on animal and human disease burden needs better understanding and new models of sapronosis disease ecology to guide the management and prevention of this important group of pathogens.

The pathophysiology of Nonketotic Hyperglycinemia (NKH), a rare neuro-metabolic disorder associated with severe brain malformations and life-threatening neurological manifestations, remains incompletely understood. Therefore, a valid human neuronal model is essential. We aimed to investigate the impact of GLDC gene variants, which cause NKH, on cellular fitness during the differentiation process of human induced pluripotent stem cells (iPSCs) into iPSC-derived astrocytes and to identify sustainable mechanisms capable of overcoming GLDC deficiency. We developed the GLDC27-FiPS4F-1 line and performed metabolomic, mRNA abundance and protein analyses. The study showed that although GLDC27-FiPS4F-1 maintained the parental genetic profile, it underwent a metabolic switch to an altered serine-glycine-one-carbon metabolism with a coordinated cell growth and cell cycle proliferation response. We then differentiated the iPSCs into neural progenitor cells (NPCs) and astrocyte-lineage cells. Analysis showed that GLDC-deficient NPCs had shifted towards a more heterogeneous astrocyte lineage with increased expression of the radial glial markers GFAP and GLAST and the neuronal markers MAP2 and NeuN. In addition, we detected changes in other genes related to serine and glycine metabolism and transport, all consistent with the need to maintain glycine at physiological levels. These findings improve our understanding of the pathology and offer new perspectives for therapeutic options.

Oxidative stress (OS) is involved in the pathogenesis of retinal neurodegenerative diseases like age-related macular degeneration (AMD) and diabetic retinopathy (DR) and an important target of therapeutic treatments. New therapeutics are tested in vivo despite limits in transferability and ethical concerns. Retina cultures using human tissue can deliver critical information and significantly reduce the number of animal experiments along with increased transferability. We cultured up to 32 retina samples derived from one eye, analyzed models’ quality, induced OS, and tested efficiency of antioxidative therapeutics. Bovine, porcine, rat, and human retinae were cultured in different experimental settings for 3-14 d. OS was induced by high-glucose or hydrogen peroxide (H2O2) and treated by Scutellarin, pigment epithelium-derived factor (PEDF), and/or granulocyte macrophage-colony stimulating factor (GM-CSF). Tissue morphology, cell viability, inflammation, and glutathione level were determined. Retina samples showed only moderate necrosis (23.83±5.05 increased to 27.00±1.66 AU PI-staining over 14 d) after 14 days in culture. OS was successfully induced (reduced ATP content of 288.3±59.9 vs. 435.7±166.8 nM ATP in controls); antioxidants reduced OS-induced apoptosis (from 124.20±51.09 to 60.80±319.66 cells/image after scutellarin-treatment). Enhanced mammalian animal and human retina cultures allow reliable, highly transferable research on OS-triggered age-related diseases and pre-clinical testing during drug development.

Cars are a highly inefficient mode of urban transport with significant negative impacts. Electric vehicles make it possible to eliminate direct CO2 emissions (though the total over a vehicle’s entire life cycle greatly offsets the advantages) but leave unchanged – or even aggravate – all the other negative effects on the quality of urban environments. Three visions for urban transport were presented: automobility, multimodality and accessibility. The first dominates North American cities, the second European one. The anomalies of these two visions have been examined. The automobility cities cannot manage the congestion and the attempts are self- defeating. The anomalies of multimodality city are related to the public space consumption for mobility and the impossibility to plan spatial proximity. The sustainable vision, that resolve the anomalies, is represented by the accessibility city in the Triple Access System (TAS) version which, however, still has a long way to go to be accepted and implemented.

This study explores how the covid-19 pandemic affected some psychological factors in people who got tattoos during or after the lockdown, the psychological factors assessed were self-esteem, risk taking behaviour, body image and locus of control. The study used a quantitative, between-subjects design to investigate the experiences of participants who acquired tattoos during the pandemic compared to those who did not. The results showed that participants who got a tattoo during the pandemic reported higher levels of self-esteem and body image satisfaction compared to those who did not get a tattoo. Furthermore, the findings suggest that individuals with tattoos may have a more external locus of control. Participants with tattoos exhibited higher levels of risk-taking behaviour compared to those without tattoos, furthermore sex affected risk-taking behaviour in tattooed individuals, and females with tattoos displayed a higher risk taking tendency than their tattooed male counterparts. Further research needs to be done while acknowledging the limitations of this study. Overall, this study is pivotal in establishing how the pandemic may have affected the aforementioned psychological factors in people with tattoos. It also adds to the growing body of literature in body modification and psychology.

Regular weight measurement is important in fattening geese to assess their health status. Failure to gain weight may indicate a potential illness. Standard weight gain analysis involves direct contact with the animal, which can cause stress to the animal, resulting in overall negative impacts on animal welfare. The focus of this study was to design a smart solution for monitoring weight changes in the breeding of farm animals. The proposed IoT system with a weighing device equipped with RFID technology for animal registration aimed to minimise the negative aspects associated with measuring in contact with humans. The designed system aims to incorporate modern approaches in animal husbandry and utilise the acquired data for the potential development of breeding approaches for various animal breeds. The system consisted of three main components: a data acquisition system, a weighing system with RFID, and an environmental monitoring system. In this study, the RFID system accuracy for detecting geese in the weighing system environment was assessed. The entire system evaluation yielded a sensitivity of 93.87%, specificity of 99.94%, accuracy of 99.85%, and precision of 95.09%. Regression analysis revealed a good correlation between observed feeding and RFID registrations with a determination coefficient of R2 = 0.9813.

In response to droughts, various media campaigns and water saving instructions are released, often however, with only temporary water conservation effects. A promising development is this regard are Digital Water Meters (DWM) that provide near real-time water-use feedback. Despite extensive DWM experience in some water-stressed regions, a profound understanding of the initial attitude towards DWM and message tailoring opportunities are rarely empirically explored. Therefore, we aim to obtain insights into the attitude towards the introduction of DWM and explore opportunities for message tailoring, a topic of extra relevance as we may be on the threshold of a large-scale implementation in many world regions. Messages tailored to (i) normative beliefs and attitudes on drinking water, (ii) water-use activity and (iii) phase of decision-making, seem particularly compatible with DWM. Through a survey (n=1037) in the Netherlands, we observe that 93% of respondents have no objections utility investments in DWM and that 78% would accept a free DWM because of improved leakage detection, lower costs and environmental considerations. Finally, instead of sociodemographic factors, we observed that an attitude-based customer segmentation approach proved an especially useful predictor of respondent’s motivation to endorse DWM and forms a promising basis for water conservation message-tailoring strategies.

Providing data on usage patterns is key to assessing the reduced-risk potential of novel tobacco and nicotine products at a population level. We performed a nationwide cross-sectional survey of the general population in Japan to assess usage patterns after the introduction of tobacco heating products (THPs). Eligible participants were Japanese residents, aged 20 years or older who consented to complete the survey. Individuals living in institutions were excluded. A three-stage probability sampling method was applied that was geographically stratified by street blocks proportionate to population density. Respondents self-reported patterns of product use and reasons for THP use. Complete responses were available from 5,306 individuals, of whom 933.5 (17.6%) were current users, 984.2 (18.5%) were former users and 3388.4 (63.9%) were never users of tobacco products. Cigarettes were used by 14.6% of current tobacco product users and THPs by 5.3%. Cigarettes and THPs were used exclusively by 64.5% and 12.2%, respectively, and both were used by 12.7%. The most common reasons reported for THP use were perceived reduction in harm to self and others compared to cigarettes. While the prevalence of cigarette use in Japan is decreasing, THPs seem to be increasingly used as long-term alternatives to cigarette smoking.

The aim was to examine the sociodemographic predictors associated with changes in movement behaviours (physical activity, screen time and sleep) among toddlers and pre-schoolers during the early stages of the coronavirus disease 2019 pandemic in Chile. Caregivers of 1- to 5-year-old children completed an online survey between March 30th and April 27th, 2020. Information about the child's movement behaviours before (retrospectively) and during the pandemic, as well as family characteristics were reported. In total, 3,157 participants provided complete data (mean children age: 3.1±1.38 years). During early stages of the pandemic, time spent in physical activity decreased, recreational screen time and sleep duration increased, and sleep quality declined. Toddlers and pre-schoolers with space to play at home and living in rural areas experienced an attenuated impact of the pandemic restrictions on their physical activity levels, screen time, and sleep quality. Older children, those whose caregivers had a higher educational level, and children living in apartments had greater changes, mainly a decrease in total physical activity and increase in screen time. This study has shown the significant impact of the pandemic restrictions on movement behaviours in toddlers and pre-schoolers in Chile.

The main objective of the study is to analyse time trends in excessive body weight (obesity, overweight) of Czech adolescents between 2002 and 2018 with regard to the socioeconomic status (SES) of adolescents’ families and to find SES-mediated correlates of adolescents’ obesity. A nationally representative sample of 29,879 adolescents (49.6% of them boys) aged 10.5-16.5 years was drawn from the Health Behaviour in School-aged Children cross-sectional, self-reported questionnaire surveys conducted in 2002, 2006, 2010, 2014, and 2018 in the Czech Republic. Across the quadrennial surveys from 2002 to 2018, we observed a clear increase in the prevalence of excessive body weight (overweight/obesity) in all SES categories of adolescents, which was most striking (p < 0.05) in adolescents with low SES (boys: +5.2/+7.5 percent points (p.p.); girls +6.3/+2.4 p.p.). When all the survey cycles were compared, the highest prevalence of overweight/obesity was evident in the low-SES adolescents in 2018, both in girls (14.9%/5.1%) and boys (20.4%/12.0%). The lower odds of obesity were significantly (p < 0.05) associated with regular vigorous physical activity, participation in organized sport. An unreasonable increase in the prevalence of obesity in adolescents with low SES suggests that national health-related and sports programmes have the least impact on children from low-SES families.

Literature is inconsistent as to how coffee affects the features of the metabolic syndrome (MetS), and which bioactive compounds are responsible for its metabolic effects. We aimed to compare the in-vivo effects of unfiltered coffee with a selected mixture of its compounds on diet-induced MetS. 24 male Sprague-Dawley rats were fed a high-fat (35% W/W) food plus 20% W/W fructose in drinking water for 14 weeks, and were randomized into three groups: control, coffee, or nutraceuticals (5-O-caffeoylquinic acid, caffeic acid, and trigonelline). Coffee or nutraceuticals were provided in drinking water in a dosage equal to 4 cups/day in a human. Compared to the controls, only coffee supplementation decreased total food intake, weight gain, and estimated average plasma glucose. Surrogate measures of insulin resistance (fasting insulin, HOMA-IR, and oral glucose tolerance) were improved at endpoint in the coffee group. Circulating triglyceride levels were also reduced by coffee. Histopathological and quantitative measurements indicated lower grades of liver steatosis after long-term coffee consumption. In conclusion, a combination of phenolic acids and trigonelline was not as effective as coffee per se in improving the components of the MetS. This points to the role of other coffee chemicals and a potential synergism between compounds.

Objective: Infliximab (IFX) concentrations are a predictive factor (PF) of pharmacokinetic (PK) origin in the treatment of Crohn’s disease (CD). We evaluated clearance, another PF of PK origin, either alone or in combination with concentrations. Methods: PF of PK origin were evaluated from two cohorts, the first received standard dosing (n=37), and the second was designed to proactively target therapeutic IFX concentrations (n=108). Concentrations were measured using homogenous mobility shift assay. Clearance was estimated using nonlinear mixed effects methods with Bayesian priors. C-reactive protein based clinical remission (<3mg/L in the absence of symptoms) was used for the disease control outcome. Longitudinal changes in disease control due to factors including time, IFX concentration, and clearance were analyzed using repeated event analysis. Change in objective function value (∆OFV) was calculated to compare concentration and clearance. Results: Lower baseline clearance and proactive dosing associated with enhanced disease control during induction (p<0.01). Higher IFX concentrations and lower Clearance measured at the second, third and fourth infusion yielded improved disease control during maintenance (p<0.032). During maintenance, the association with disease control was better with clearance than with concentrations (∆OFV= -19.2; p<0.001), and the combination of both further minimized OFV (p<0.001) with markedly improved clinical yield in the presence of both PF of PK origin. Conclusion: PF of PK origin and lower clearance during induction and maintenance yielded enhanced disease control in pediatric CD treated with IFX. The combination of IFX concentration and clearance are better predictors of therapeutic outcome compared to either one alone.

Over the last decade, advances in our understanding about the genetic architecture of complex traits and common diseases, have increased our ability to perform susceptibility genetic testing for diseases in asymptomatic individuals. These technological developments raise complex ethical, legal and social considerations. Here we discuss a series of ethical issues associated with susceptibility genetic testing for Alzheimer's and Parkinson's disease. These include, amongst others, informed consent, disclosure of results and unexpected findings, mandatory screening, privacy and confidentiality, and stigma and genetic discrimination. As knowledge of the genetic basis of these diseases continues growing, and as genetic testing becomes more widespread, we anticipate that it will become increasingly important for scientists and clinicians to engage in the conversation about the ethical, social and policy implications of these technologies.

Background: Meniere's disease (MD) has been recently linked to gluten assumption. Approximately 75% of MD patients show positive skin test to food and about 50% of the positive responses are specific to the gliadin acid extract fraction. Aim of this study was to investigate the humoral immune responses to wheat antigens and related autoantigens in MD patients. Methods. We assessed the reactivity of sera from 28 patients with definite MD and 100 healthy controls against a repertoire of 51 antigens usually associated with immune reaction to gluten. Results. MD patients showed an increase of anti-wheat IgA, anti-cerebellar peptide IgA and anti-glutamic acid decarboxylase (GAD) 65 IgM compared to healthy controls. In particular, the increase of anti-wheat IgA and GAD 65 IgM has been confirmed in a subgroup of MD patients symptomatically responding to a gluten free diet (GFD). Conclusion. In MD patients, an increase of the antibody production against gluten biomarkers was observed; in particular, anti-wheat IgA seems to be associated to clinical response to GFD.

We have considered a SEIR-SEI Vector-host mathematical model which captures malaria transmission dynamics, described and built on 7-dimensional nonlinear ordinary differential equations. We compute the basic reproduction number of the model; examine the positivity and boundedness of the model compartments in a region using well established methods viz: Cauchy’s differential theorem, Birkhoff & Rota’s theorem which verifies and reveals the well-posedness, and carrying capacity of the model respectively, the existence of the Disease-Free (DFE) and Endemic (EDE) equilibrium points were determined and examined. Using the Gaussian elimination method and the Routh-hurwitz criterion, we convey stability analyses at DFE and EDE points which indicates that the DFE (malaria-free) and the EDE (epidemic outbreak) point occurs when the basic reproduction number is less than unity (one) and greater than unity (one) respectively. We obtain a solution to the model using the Variational iteration method (VIM) (an unprecedented method) to each population compartments and verify the efficacy, reliability and validity of the proposed method by comparing the respective solutions via tables and combined plots with the computer in-built Runge-kutta-Felhberg of fourth-fifths order (RKF-45). We illustrate the combined plot profiles of each compartment in the model, showing the dynamic behavior of these compartments; then we speculate that VIM is efficient and capable to conduct analysis on Malaria models and other epidemiological models.

Neurodegenerative diseases are multifactorial, initiated by a series of the causative complex which develops into a certain clinical picture. The pathogenesis and disease course vary from patient to patient. Thus, it should be likewise to the treatment. Peripheral biomarkers are to play a central role for tailoring a personalized therapeutic plan for patients who suffered from neurodegenerative diseases such as Alzheimer’s diseases, Parkinson’s disease, and multiple sclerosis, among others. Nevertheless, the use of biomarkers in clinical practice is still underappreciated and data presented in biomarker research for clinical use is still uncompelling, compared to abundant data available for drug research and development. So is the case with kynurenines (KYNs) and the kynurenine pathway (KP) enzymes which have been associated with a wide range of diseases including cancer, autoimmune diseases, inflammatory diseases, neurologic diseases, and psychiatric disorders. This review article discusses current knowledge of the KP alteration observed in the central nervous system as well as the periphery, its involvement in pathogenesis and disease progression, and emerging evidence of roles of microbiota to the gut-brain axis, searching for practical peripheral biomarkers which ensure personalized treatment plans for neurodegenerative diseases.

Statistical modeling of lifetime data plays an essential role in a wide range of practical fields, such as health and engineering. There have been a lot of studies done to develop statistical models that can better describe health data than traditional models. For the first time, we pioneer a novel family of continuous probability distributions called the generalized odd beta prime generalized (GOBP-G) family of distributions. The cumulative distribution and probability density functions of the new family are presented. A new generalization of the Weibull distribution called "generalized odd beta prime-Weibull" (GOBPW) is proposed using the pioneered GOBP-G family. The mixture representations of the new distribution are defined and derived. Some formal statistical properties of the GOBPW distribution, such as the moments, moment generating function, incomplete moments, information generating function, entropies, stress-strength function, quantile function, and order statistics, are derived. The estimation of the parameters of the proposed distribution is evaluated using the maximum likelihood estimation approach. Different cancer disease data sets, such as the bladder, head and neck, acute bone, and blood cancers, are used to illustrate the applicability and usefulness of the new model and were compared using several statistical accuracy measures with that of well-established extended Weibull distributions, which are the beta modified Weibull distribution, Kumaraswamy modified Weibull distribution, gamma generalized modified Weibull distribution, gamma log-logistic Weibull distribution, and beta log-logistic Weibull distribution. The results show that the proposed model gives better results than the competitive models. This study could guide the relevant stakeholders in choosing a suitable statistical model for the health data instead of relying on traditional models to enhance decision-making.

The social- and self-directed behaviours of two golden lion tamarins (Leontopithecus rosalia) was investigated while having residence in the tropical house of Aalborg Zoo, Denmark. The behaviour of the female had been distinct from the male since 2018. Despite several diagnostic examinations and medicinal treatments, the cause of the aberrant and apparently stereotypical behavioural patterns remained undetermined, which initiated this study. The pair were recorded throughout a predetermined observation period and these recordings were analysed to illuminate the behaviours of the individuals. The results showed that there were differences in the type, frequency, and durations of both social- and self-directed behaviours between the sick female and the healthy male. The female expressed both social- and self-directed behaviours more frequently and for longer durations, while the male were more socially reserved and did not engage in social behaviours as frequently. Furthermore, subsequent necropsy of the female revealed uro-genital disease.

Locoregional anaesthetic techniques are invaluable for providing multimodal analgesia for painful surgical procedures. This prospective, randomised study describes a nerve stimulator-guided bra-chial plexus blockade (BPB) in rabbits undergoing orthopaedic surgery in comparison to systemic lidocaine. Premedication was provided with intramuscular (IM) medetomidine, fentanyl and midazolam. Anaesthesia was induced (propofol IV) and maintained with isoflurane. Nine rabbits received a lidocaine BPB (2%; 0.3 ml kg-1), and eight received lidocaine constant rate infusion (CRI) (2 mg kg-1 IV, followed by 100 µg kg-1 minute-1). Rescue analgesia was provided with Fentanyl IV. Carprofen was administered at the end of surgery. Post-operative pain was determined using the Rabbit Grimace Scale (RGS) and a composite pain scale. Buprenorphine was administered accord-ing to pain score for two hours after extubation. Rabbits were filmed during the first two hours to measure distance travelled and behaviours. Food intake and faeces output were compared. Every rabbit in CRI required intraoperative rescue analgesia compared to no rabbits in BPB. How-ever, rabbits in both groups had similar pain scores and there was no difference in administration of postoperative analgesia. There were no significant differences in food intake or faeces produc-tion over 18 hours, and no significant differences in distance travelled, or behaviours examined during the first two hours. BPB seems superior for intraoperative analgesia. Postoperatively both groups were comparable.

Few young Japanese adults regularly consume a well-balanced diet composed of staples, course dishes, and sides. We hypothesised that adopting the recommended planetary health diet with regular breakfast consumption would promote well-balanced diets among young Japanese male undergraduates. This study aimed to examine the structural association between a planetary health diet with regular breakfast consumption and well-balanced diet intake. Participants were 142 male undergraduates who completed a 2022 online questionnaire via Google Forms in a cross-sectional study at a public university in Hyogo Prefecture. A planetary health diet comprises the consumption of the recommended eight items. A covariance structure analysis was performed in a hypothetical model with factors (regular breakfast consumption and eight items) potentially associated with the intake of a well-balanced diet at least twice daily. Acceptable goodness-of-fit was obtained by excluding chicken dishes and nuts from the eight recommended items of the planetary health diet. Frequent consumption of the remaining six recommended items (fish, eggs, soybeans/soybean products, dairy foods, vegetables, and fruits) was significantly positively correlated with regular breakfast consumption and a significant positive path to a well-balanced diet. Among male university students, regular breakfast consumption and a planetary health diet may lead to a well-balanced diet.

The present study investigates the decision-making process of investors on the Pakistan Stock Exchange with regard to portfolio construction, explicitly focusing on the incorporation of ESG concerns. The present study employed SmartPLS and structural equation modeling (SEM) to quantitatively assess data received from a sample of 393 out of 400 respondents. Based on the available data, investors participating in the Pakistan Stock Exchange are notably impacted by ESG aspects. The findings of this study hold significance for emerging economy firms, regulators, and investors, both in terms of theoretical and practical ramifications. The study's findings demonstrate a clear indication of investors' significant emphasis on ESG matters. Furthermore, it provides valuable insights for stakeholders who are involved in the ever-evolving realm of sustainable finance within developing countries

The health of inmates living in a restricted environment are affected by oral health behaviours and is related to their oral health-related quality of life (OHRQoL). We investigated oral health behaviours and oral symptoms among male inmates and analysed factors related to OHRQoL. Three hundred and seventy-six male inmates in two prisons were investigated using a self-reported questionnaire. The survey items included oral health behaviours, oral symptoms, self-esteem, and OHRQoL level. We analysed cross-correlations and factors related to OHRQoL. Toothbrushing after lunch and dinner was practiced by 83.5% of male inmates. ‘Food impaction’ was experienced by 45.4%. The OHRQoL level among male inmates was low, at 39.90 points. A hierarchical multiple regression model that controlled for general characteristics identified the following OHRQoL factors, in order of significance: trouble biting/chewing (β = -0.307), toothache (β = -0.154), temporomandibular joint disorder (β = -0.099), and periodontal health (β = 0.089). Self-esteem and OHRQoL were not significantly correlated. To ensure oral health in male inmates, the results of this study suggests that an oral health education programme, as well as provision of adequate dental care services, is required to increase appropriate oral health practice rates.

Work in the copper mining industry is often associated with exposure to respirable dust and respirable crystalline silica. This exposure has the potential to cause silicosis, a non-curable occupational respiratory lung disease. This study aimed at establishing the relationship between knowledge, attitudes, work behaviour and practice, compliance with safety standards and exposure to respirable dust. A cross-sectional descriptive survey was conducted on 528 mine workers. Statistical package for social sciences (SPSS) was used for descriptives. Structural Equation Modelling (SEM) with latent variables and partial least-squares (LVPLS) analysis was employed to determine the relationship among these variables. The results indicated that of the four (4) hypotheses, two (2) were supported and two (2) were rejected showing that there is a significant relationship between exposure to respirable dust and work behaviour and practice, as well as compliance with safety standards. Knowledge and attitudes towards respirable dust exposure did not significantly influence exposure. According to the results from the survey, positive work behaviour and practice as well as compliance with safety standards was significantly associated with exposure to respirable dust. It is recommended that the mine should focus on the miners’ work behaviour and practice and compliance with safety standards.

Studying Active Transportation (AT) is widespread in America and Europe's research and stud-ies that include Latent variables (LV) are growing to identify exact results of finding what to do to increase the utility of AT. LVs help us to have more accurate research. LVs are defined as psy-chological factors like feeling safe while you ride at night and thus they are not subjective and hard to understand but very important to increase the utility of using AT modes. In this study, most of the previous studies about bicycling have been reviewed. In this research, different var-iables including subjective and LVs are conducted for maximizing the use of bicycle utility and introduced to have better sight for future researchers to deal with modeling AT mode choice. Results represent the importance of having 'will' for using a bicycle, especially in difficult situa-tions and cultural barriers that affect the cycling of women.

As a mediator variable, self-confidence is one of the most effective elements of the decision-making process of consumer behaviour. This research has studied the effects of different aspects of consuming fashion on the self-confidence and behaviour of consumers in Tehran’s clothing market. This study has considered the acceptance of new products, interest in mode and fashion, utilitarianism, and personal taste in its analysis. This research aims to understand the fashion buying behaviour amongst Iranian consumers in consideration of their attitude towards self-confidence and aspects of fashion consumption. The statistic sample is 400 consumers from Tehran’s clothing market who have been chosen based on the random availability procedure. The primary tool in this research was a questionary used to testify the assumptions and a model fit created by using structural equations and factor analysis. This research showed that the interest in mode and fashion, personal taste, utilitarianism, and new products positively impact self-confidence. In addition, the positive impact of self-confidence on fashion buying behaviour was confirmed.

The cyclic load applied to civil and mining structures can lead to a reduction of the materials’ strength, different from that which would occur with a monotonous load. Numerous cases can be found where the decay of the rock parameters subjected to this type of stress leads to progressive or sudden collapse: among them, tunnel walls, pillars and slabs in mining operations, roads with a heavy vehicle transit, abutments of bridges and dams can be quoted. The topic can therefore be fundamental for a correct structural design, to avoid problems during the life of the structure. However, given the heterogeneity of the rock materials and the difficulty of their characterization under this aspect, an unequivocal analysis is hardly achievable. Then, the discussion initially develops through a general historical review of the concept of fatigue, with a synthetic collection of case histories. The laboratory tests on rock samples are then examined and the most important results obtained are discussed. Finally, a comparison between different types of tests is proposed. The experimental data are expressed through the Wӧhler diagram. The goal is to fill the lack of design codes or standards in the field of cyclic stresses applied to rock materials, the understanding of its effect being of great interest in order to apply suitable parameters in the design phase.

Concrete has become the most common construction material showing among other advantages good behaviour when subjected to high temperatures. Nevertheless, concrete is usually reinforced with elements of other materials such as steel in the form of rebars or fibres. Thus, the behaviour under high temperatures of these other materials can be critical for structural elements. In addition, concrete spalling occurs when concrete is subjected to high temperature due to internal pressures. Micro polypropylene fibres (PP) have shown to be effective for reducing such spalling although this type of fibres barely improve any of the mechanical properties of the element. Hence, a combination of PP with steel rebars or fibres can be effective for the structural design of elements exposed to high temperatures. New polyolefin fibres (PF) have become an alternative to steel fibres. PF meet the requirements of the standards to consider the contributions of the fibres in the structural design. However, there is a lack of evidence about the behaviour of PF and elements made of polyolefin fibre reinforced concrete (PFRC) subjected to high temperatures. Given that these polymer fibres would be melt above 250 °C, the behaviour in the intermediate temperatures was assessed in this study. Uni-axial tests on individual fibres and three-point bending tests of PFRC specimens were performed. The results have shown that the residual load-bearing capacity of the material is gradually lost up to 200 °C, though the PFRC showed structural performance up to 185°C.

The driving force behind adopting the idea of ​​sustainable development are producers and retailers. Unfortunately, when preparing their product range for consumers, many of them still only pay attention to the size of the customers’ earnings, how often they shop and how much they buy when shopping. In consumer segmentation, sustainable values ​​that consumers apply when making their purchasing decisions are rarely taken into account. The aim of this article is to show that values ​​such as environmental protection, the ethical behaviour of producers, fair trade or maximising the utility function of consumption are so important in the purchasing process in the coffee market that they can be used as segmentation variables. The Polish coffee market was selected to carry out segmentation taking into account the consumers' sustainable values. The main source of the article is the results of a standardized online survey conducted on a nationwide sample of 800 coffee consumers in July 2018. Multi-dimensional analyses such as extrapolative factor analysis (EFA) and cluster analysis (CA) were used to describe the obtained results. As a result, six segments of coffee consumers were identified and described: “responsible, aspiring to be connoisseurs”, “loyal coffee enthusiasts”, “pragmatic users”, “coffee laypersons”, “sophisticated connoisseurs”, “consumerists, connoisseurs, but not at any price”. Among the identified segments, the sustainable consumption values ​​most often mentioned refer to "responsible, aspiring to be connoisseurs", and the least often - ”consumerists, connoisseurs, but not at any price”. The conclusions presented in the last part of the article may be used by manufacturing and trade enterprises, operating on the coffee market, in order to respond to the identified needs and expectations of consumers and by governmental and social organisations so as to determine the directions of pro-ecological education of consumers.

Education and awareness raising are the primary tools of global health policy to change public behaviour. Considering the limitations of awareness agenda and the lack of social research to inform alternative approaches, our objective was to generate new empirical evidence on the consequences of antibiotic-related awareness raising in a low-income country context. We implemented an educational activity in two Lao villages to share general antibiotic-related messages, but also to learn about people’s conceptions and health behaviours. Two rounds of census survey data enabled us to assess the activity’s outputs, its knowledge outcomes, and its immediate behavioural impacts in a difference-in-difference design. Our panel data covered 1,130 adults over two rounds, including 58 activity participants and 208 villagers exposed indirectly via conversations in the village. We found that activity-related communication circulated among more privileged groups, which limited its indirect effects. Among participants, the activity influenced the awareness and understanding of “drug resistance,” while effects on attitudes were minor. Evidence on behavioural impacts was sparse and mixed, but the range of possible consequences included a disproportionate uptake of antibiotics from formal healthcare providers. Our study casts doubt on the continued dominance of awareness raising as a behavioural tool to address antibiotic resistance.

Background: Gut-Brain-Axis provides bidirectional communicational route; imbalance of which can have pathophysiological consequences. It is a frontier in autism research, affects 85% of autistic children (NIH report). Their microbiome has few overall microbes and smaller number of health promising microbes than their neurotypical peers. We hypothesize autism gut might play a role in manifestation of autism behaviours and on treatment, can revert back to normal behaviour considerably. The aim is to better understand to what degree gut microbiota of autism subjects differs from controls and identify bacterial species present exclusively in autism. Materials and Methods: 16s-rRNA-sequence of autism-subjects were retrieved from the American Gut Project Archive. Taxonomic assignment was inferred by similarity based methods using Quantitative Insights Into Microbial Ecology (QIIME). Species abundance was characterized and co-occurrence network was built to infer species interaction using measures of diversity. Statistical parameters were considered to validate the findings. Result: A total of 206 (1.8%) of American Gut Project datasets onstituted of autistic samples. Various bacteria such as Akkermansia sp., and Prevotella sp., were harboured in higher abundance in autistic children with statistical significance than in controls. Conclusion: These findings indicate connecting-link between gut-microbiome-brain-axis and autistic behaviour which can result in improved management

Iterated games, in which the same economic interaction is repeatedly played between the same agents, are an important framework for understanding the effectiveness of strategic choices over time. To date very little work has applied information theory to the information sets used by agents in order to decide what action to take next in such strategic situations. This article looks at the mutual information between previous game states and an agent's next action by introducing two new classes of games: ’invertible games’ and ‘cyclical games'. By explicitly expanding out the mutual information between past states and the next action we show under what circumstances these expressions can be simplified. These information measures are then applied to the Traveler's Dilemma game and the Prisoner's Dilemma game, the Prisoner's Dilemma being invertible, to illustrate their use. In the Prisoner's Dilemma a novel connection is made between the computational principles of logic gates and both the structure of games and the agents' decision strategies. This approach is applied to the cyclical game Matching Pennies to analyse the foundations of a behavioural ambiguity between two well studied strategies: ‘Tit-for-Tat' and ’Win-Stay, Lose-Switch'.

Background: Acute kidney disease (AKD) is a known risk factor for increased mortality and evolution towards chronic kidney disease (CKD) in adults. The data regarding children are scarce. The purpose of our study is to explore the risk factor for AKD and impact of AKD following an acute kidney injury (AKI) episode in children on mortality and new-onset CKD. Methods: We retrospectively evaluated 736 children with ages between 2 and 18 years old with AKI admitted in a tertiary care hospital from the west Romania over a 9 years period. Results: AKD incidence following AKI was 17%. Patients that developed AKD were older, with higher baseline serum creatinine values, urea, C reactive protein and lower proteins, haemoglobin and sodium. They were more often exposed to sepsis, critical illness and nephrotoxic medications and presented certain susceptibilities like CKD, neoplasia, anemia, heart failure, arterial hypertension, stem cell transplant and female gender. AKI causes that increased the risk of AKD were intrinsic ones. AKD increased the overall mortality by three times. The factors that independently increased the risk of evolution towards CKD were AKD, acute tubular necrosis and higher baseline serum creatinine values. Conclusions: AKD is an independent risk factor for mortality and new-onset CKD in children.

Introduction: Sarcopenia, muscle loss, often coexists with MASLD, a common liver disorder, which is more prevalent in those with sarcopenia. Sarcopenia also increases the risk of liver conditions like steatosis and fibrosis. Studies on sarcopenia in MASLD are common in developed countries, but fewer follow the EWGSOP2 guidelines in Brazil. Aim: to assess sarcopenia prevalence in MASLD patients. Methods: Cross-sectional study conducted at the Gastroen-terology/Hepatology Service of ISCMPA with patients diagnosed with MASLD. The EWGSOP2 criteria were used to evaluate sarcopenia. Categorical data presented as absolute and relative frequency; parametric continuous data ex-pressed as mean±standard deviation; non-parametric continuous data as me-dian and IQR. Gender differences in were analyzed using Fisher's Exact Test or Chi-squared tests, and for continuous variables, T Student tests (parametric) and Mann-Whitney U tests for independent samples (non-parametric). The significance level was set at 5% (p<0.05). Results: The study involved 103 MASLD patients with an average age of 60.39 years, comprising 48 (46.60%) adults and 55 (53.40%) older individuals. Concerning sarcopenia diagnosis, four individuals exhibited decreased muscle strength; two had reduced MME (sarcopenia); and one showed decreased walking speed (severe sarcopenia). Among the participants, 63 (60.6%) were physically active. 35 (62.5%) had mild to moderate steatosis, while 21 (37.5%) had severe steatosis. In terms of EHNA, 13 subjects (24.08%) had moderate to severe EHNA. Regarding fibrosis classi-fication, 68 (72.34%) individuals had undetermined or high probability based on the NAFLD score, with higher prevalence in males (n=23; 88.5%). Fibrosis assessment via liver biopsy revealed 27 (28.72%) in F1 and F2 and 15 (16.96%) in F3 and F4. Stratification of fibrosis into F3 and F4 was more com-mon among men (n=9; 47.4%). Conclusion: Most of the population was physi-cally active. The parameters indicating sarcopenia exceeded the thresholds recommended by EWGSOP2. The prevalence of sarcopenia was low in individuals with MASLD.

Background: The current review was conducted to determine the effectiveness of atenolol on all-cause mortality rate among Asian patients with chronic progressive diseases, mainly diabetes mellitus, primary hypertension, and coronary artery disease. Methods: We searched the COCHRANE, MEDLINE, TRIP, and EMBASE databases for published articles up to 31 March 2023. Studies that compared all-cause mortality rates among Asian patients who were on atenolol or other medications were included. Results: The review included 79603 Asian patients from three cohort studies. Out of the studied patients, 36046 were atenolol users and 43557 were non-atenolol users. The review revealed that atenolol users recorded lower all-cause mortality rates compared to non-users with a significant difference (OR= 0.57, CI= 0.44-0.75, P<0.001). The pooled estimate of the all-cause mortality rate was also lower among atenolol users (7.02%) compared to metoprolol tartrate users (13.15%) with a significant difference (OR= 0.50, CI= 0.47-0.53, p < 0.0001). Although the included studies were categorized as having a low risk of bias for most of the studied domains, significant heterogeneity was recorded across these studies (I2 =88%, P=0.001). Conclusion: This review found that atenolol when compared to a control or metoprolol tartrate, has a significant effect in reducing the all-cause mortality rate among Asian patients with chronic progressive disease.

Choroid plexus insufficiency or glymphatic stasis are often classified as prequels to harmful accretion of toxic proteins in neurodegenerative disease. Cognitive decline and memory loss subsequently become cardinal features of Alzheimer’s disease (AD), typically progressing with amyloid-ß and tau protein accumulation. For Parkinson’s disease (PD), α-synuclein deposits and dopamine depletion are linked to impaired movement, resting tremor, and rigidity. Importantly, both diagnoses are accompanied by hyperinflammation and intrathecal cytokine changes. Thus far, numerous clinical trials for investigational drugs have produced nothing effective for AD or PD, yet the anti-inflammatory and regenerative potential of platelet-rich plasma (PRP) remains largely unexamined in this context. This report explores a proposed Phase I study on intrathecal condensed plasma growth factors processed from autologous thrombin-activated PRP as monotherapy for AD or PD. The concept gains support from related work where cytokines of platelet origin successfully lowered inflammation, corrected background fibrosis, deactivated abnormal cells, and recovered local tissue function—all desirable outcomes in AD and PD. PRP-mediated effects on membrane potentials, electrolyte balance, and water clearance are less well characterized, but experimental evidence suggests these pathways could likewise influence glymphatic drainage to ameliorate proteinopathies. As a well-tolerated ‘orthobiologic’ with no hypersensitivity risk, intrathecal PRP and its derivatives bring advantages distinct from synthetic pharmaceuticals. If age-associated neuroinflammation in AD and PD is an upstream event contributing to neural disruption, then dampening local oxidative stress by a patient’s own platelet cytokines (as already proven in other tissues) could offer therapeutic relevance to these neurodegenerative conditions as well.

Crop disease classification has always been a critical and persistent problem in the field of agricultural and forestry sciences, where often we do not have access to a sufficient number of samples to know the distribution of real-world samples. How to make full use of the existing data is the starting point of our thinking. To address this problem, this paper proposes a supervised image augmentation method Negative Contrast, which uses the contrast images of existing disease samples after removing disease areas as negative samples for image augmentation when samples are relatively scarce. Numerous experiments have shown that several classical models using this augmentation method have improved in disease classification of four crops, rice, wheat, corn, and soybean, with a maximum accuracy improvement of 30.8%. In addition, the comparative analysis of attentional heat map shows that the model using Negative Contrast is more accurate and intense on the area of interest of diseases, and thus reflects better generalization ability in real-world disease classification. Our dataset and codes can be found in https://www.kaggle.com/datasets/w970704112/corn-wheat-rice-soybean and https://github.com/hiter0/contrastaug .

Concomitant neuropathological hallmarks of Alzheimer’s Disease (AD) are common in the brains of people with Parkinson’s disease (PD). Furthermore, AD biomarkers are associated with cognitive decline and dementia in PD patients during life. Here, we highlight the considerable overlap between AD and PD, emphasizing neuropathological, biomarker, and mechanistic studies. We suggest that precision medicine approaches may successfully identify PD patients most likely to develop concomitant AD. The ability to identify PD patients at high risk for future concomitant AD in turn provides an ideal cohort for trials of AD-directed therapies in PD patients, aimed at delaying or preventing cognitive symptoms.

Assessment of cardiac function is the leading parameter when evaluating the state of the cardiovascular system of patients undergoing chronic hemodialysis. The aim of the paper: to assess the state of the cardiovascular system of these patients using new sensitive echocardiography and Doppler techniques and thus advance the prevention of cardiovascular disease.Method: Twenty children with end-stage renal insufficiency on chronic hemodialysis and twenty healthy controls underwent echocardiographic monitoring using standard Doppler and tissue Doppler imaging. Structural and functional changes in the left ventricle were evaluated.Results: Patients on hemodialysis had significantly greater left ventricular mass indices compared to the controls (p<0.001). The patients on hemodialysis had preserved systolic function – their fractional shortening, ejection fraction and Sm (systolic myocardial velocity) did not differ significantly compared to the controls (p>0.05). Early diastolic function in children on hemodialysis was also preserved: the E/A and Em/Am ratio did not differ significantly from the control group (p>0.05). Children on hemodialysis exhibited impaired late diastolic function (compliance index), that is, considerably higher E/Em compared to controls (p<0.00). Myocardial Performance Index values showed statistically significant elevation in children on hemodialysis compared to the control group (p<0.001).Conclusion: Tissue Doppler in tandem with conventional Pulsed Doppler can provide additional information on left ventricular filling pressures (E/Em) in children on hemodialysis. It is therefore recommended to perform routine measuring of Em waves and the E/Em ratio, not only in order to evaluate myocardial relaxation and ventricular filling pressures, but primarily to stratify risk and provide a prognosis.

Google Trends data can be informative for infectious disease incidences, including Lyme disease. However, the use of Google Trends for predictive purposes is underutilized. In this study, we tested the ability of Google Trends search data to predict monthly state-level Lyme disease case counts in the United States. We requested Lyme disease data for the years 2010-2021. We downloaded Google Trends search data on terms for Lyme disease, symptoms of Lyme disease, and diseases with similar symptoms as Lyme disease. We built mixed negative binomial models based on a training dataset (2010-2016) and tested the models on a test dataset (2017-2021). A model was built for each search term and monthly lags of search terms were included as predictors. The highest performing models had high predictive ability, indicated by low Root Mean Squared Errors (RMSEs) and close association between observed and predicted case counts. The highest performing model was for the search term “Summer Flu”, which indicates low specificity of some of the terms. We outline challenges of using Google Trends data, including data availability and a mismatch between geographic units. We discuss opportunities for Google Trends data, including prediction of additional zoonotic diseases and incorporating environmental and companion animal data.

Neutrophils are the principal trouper of innate immune system. Activated neutrophils undergo a noble cell death termed NETosis and release a mesh-like structure called neutrophil extracellular traps (NETs) as a part of their defensive strategy against microbial pathogen attack. This web-like architecture includes a DNA backbone embedded with antimicrobial proteins like myeloperoxidase (MPO), neutrophil elastase (NE), histones etc. and deploys in the entrapment and clearance of encountered pathogens. Thus NETs play an inevitable beneficial role in the host's protection. However, recent accumulated evidence shows that dysregulated and enhanced NET formation has various pathological aspects including promotion of sepsis, pulmonary, cardiovascular, hepatic, nephrological, thrombotic, autoimmune, pregnancy, cancer diseases etc. and the list is increasing gradually. In this review, we summarize NETs mediated pathophysiology of different diseases, focus on some updated potential therapeutic approaches against NETs and share our future perspectives.

The Neurodegenerative Diseases are, according to recent studies, one of the main causes of disability and death worldwide. Interest in molecular genetics has started to have an exponential growth thanks to numerous advancements in tech, shifts in the understanding of the disease as a phenomenon, and the change of perspective regarding gene editing and the upsides of this action. The aim of this paper is to analyse the newest approaches in genetics and molecular sciences regarding four of the most important neurodegenerative disorders: Alzheimer’s Disease, Parkinson’s Disease, Huntington’s Disease and Amyotrophic Lateral Sclerosis. We intend through this review to focus on the newest treatment, diagnosis and predictions plans regarding this large group of diseases, in order to obtain a better accuracy analysing and spotting the emerging signs that could lead to a better outcome in order to increase both the quality and the life span of the patient. Moreover, this review could provide future evidence of possible novelty therapies that target the specific genes and could be useful to be taken into consideration when the classical approaches fail to shed light.

Neurodegenerative diseases (NDs) are a set of progressive, chronic, and incurable diseases characterized by the gradual loss of neurons, culminating in the decline of cognitive and/or motor functions. Alzheimer’s disease (AD) and Parkinson’s disease (PD) are the most common NDs and represent an enormous burden both in terms of human suffering and economic cost. The available therapies for AD and PD only provide symptomatic and palliative relief for a limited period and are unable to modify the diseases’ progression. Over the last decades, research efforts have been focused on developing new pharmacological treatments for these NDs. However, to date, no breakthrough treatment has been discovered. Hence, the development of disease-modifying drugs able to halt or reverse the progression of NDs remains an unmet clinical need. This review summarizes the major hallmarks of AD and PD and the drugs available for pharmacological treatment. It also sheds light on potential directions that can be pursued to develop of new, disease-modifying drugs to treat AD and PD, thereby decreasing the social and economic burdens linked to these NDs.

Many of the potential immune therapeutic targets are similarly affected in adult-onset neurodegenerative diseases such as Alzheimer’s (AD) disease, Parkinson’s disease (PD), amyotrophic lateral sclerosis (ALS), and frontotemporal dementia (FTD), but also in a seemingly distinct Niemann-Pick type C disease with primarily juvenile-onset. This strongly argues for an overlap in pathogenic mechanisms. The commonly researched immune targets include various immune cell subsets such as microglia, peripheral macrophages, or regulatory T cells (Tregs), the complement system, and other soluble factors. In this review, we will compare these neurodegenerative diseases from a clinical point of view and point out the common pathways and mechanisms of protein aggregation, neurodegeneration and/or neuroinflammation that could potentially lead to shared treatment strategies. We also describe the common therapeutic approaches in treating the immune dysfunctions in these disorders, moving from immunization to microbiome regulation and stem cell treatment.

Neurodegenerative diseases such as Alzheimer's disease, Parkinson's disease, Huntington's disease, and Amyotrophic Lateral Sclerosis are heterogeneous, progressive diseases with frequently overlapping symptoms characterized by a loss of neurons. Studies suggested relations between neurodegenerative diseases for many years, e.g., regarding the aggregation of toxic proteins or triggering endogenous cell death pathways. Within this study, publicly available genomic, transcriptomic and proteomic data were gathered from 188 studies and more than one million patients to detect shared genetic patterns between the neurodegenerative diseases and the analyzed omics-layers within conditions. The results show a remarkably high number of shared genes between the transcriptomic and proteomic levels for all diseases while showing a significant relation between genomic and proteomic data only in some cases. A set of 139 genes was found to be differentially expressed in several transcriptomic experiments of all four diseases. These 139 genes showed overrepresented GO-Terms and pathways mainly involved in stress response, cell development, cell adhesion, and the cytoskeleton. Furthermore, the overlap of two and three omics-layers per disease were used to search for overrepresented pathways and GO-Terms. Taken together, we could confirm the existence of many relations between Alzheimer's disease, Parkinson's disease, Huntington's disease, and Amyotrophic Lateral Sclerosis on the transcriptomic and proteomic level by analyzing the pathways and GO-Terms arising in these intersections. The significance of the connection between the transcriptomic and proteomic data for all four analyzed neurodegenerative diseases showed that exploring these omics-layers simultaneously holds new insights that do not emerge from analyzing these omics-layers separately. Our data therefore suggests addressing human patients with neurodegenerative diseases as complex biological systems by integrating multiple underlying data sources.

Gaucher disease (GD) is a lysosomal storage disorder stemming from biallelic mutations in GBA1, characterized by glucocerebrosidase dysfunction and glucocerebroside and glucosylsphingosine accumulation. Since phenotypes of murine models of GD often differ from those in patients, careful characterization of Gba1 mutant mice is necessary to establish their ability to model GD. We performed side-by-side comparative biochemical and pathologic analyses of four murine Gba1 models with genotypes L444P/L444P (p.L483P/p.L483P), L444P/null, D409H/D409H (p.D448H/p.D448H), and D409H/null, along with matched wildtype mice, all with the same genetic background and cage conditions. All mutant mice exhibited significantly lower glucocerebrosidase activity (p < 0.0001) and higher glucosylsphingosine levels than wildtype, with the lowest glucocerebrosidase and highest glucosylsphingosine levels in mice carrying a null allele. Although glucocerebrosidase activity in L444P and D409H mice was similar, D409H mice showed more lipid accumulation. No Gaucher or storage-like cells were detected in any of the Gba1 mutant mice. Quantification of neuroinflammation, dopaminergic neuronal loss, alpha-synuclein levels and motor behavior revealed no significant findings, even in aged animals. Thus, while the models may have utility for testing the effect of different therapies on enzymatic activity, they did not recapitulate the pathological phenotype of patients with GD, and better models are needed.

Background: Autoimmune inner ear disease (AIED) is a rare autoimmune condition characterized by progressive sensorineural hearing loss with hearing fluctuations over weeks to months, presenting significant challenges in both diagnosis and treatment. Due to its rarity, treatment responses and prognosis in AIED remain poorly understood. Methods: This study reviewed medical records from Taipei Medical University Hospital documented between August 2016 and August 2021. Among 67 patients experiencing fluctuating hearing loss, 11 met the diagnostic criteria for AIED and underwent regular follow-up assessments within a 5-year timeframe. ROC curve was used to discriminate the power of these prognostic parameters. Results: In this study, several factors including younger age, milder initial hearing loss, meeting criteria for bilateral Meniere's disease (MD), having an ascending audiogram pattern, longer time interval between hearing impairment attacks in contralateral ears and responding well to steroids were associated with better prognosis. ROC curve demonstrated the diagnostic value of specific parameters such as the presence of bilateral MD (AUC 0.825, 95% CI 0.640–1.000), pretreatment HI ≤ 45 dB HL (AUC 0.808, 95% CI 0.610–1.000), response to steroids (AUC 0.800, 95% CI 0.595–1.000), and ascending audiogram (AUC 0.858, 95% CI 0.683–0.858). Conclusions: This study identified key prognostic factors for AIED, providing valuable insights for predicting AIED prognosis and facilitating personalized patient management.

Inflammatory Bowel Disease (IBD) presents distinct challenges during pregnancy due to its influence on maternal health and pregnancy outcomes. This literature review aims to dissect the existing scientific evidence on pregnancy in women with IBD and provide evidence-based recommendations for clinical management. A comprehensive search was conducted across scientific databases, selecting clinical studies, systematic reviews, and other pertinent resources. Numerous studies have underscored an increased risk of complications during pregnancy for women with IBD, including preterm birth, low birth weight, neonates small for gestational age, and congenital malformations. Nevertheless, it's evident that proactive disease management before and throughout pregnancy can mitigate these risks. Continuation of IBD treatment during pregnancy and breastfeeding is deemed safe with agents like thiopurines, anti-TNF, vedolizumab, or ustekinumab. However, there's a call for caution when combining treatments due to the heightened risk of severe infections in the first year of life. For small molecules, their use is advised against in both scenarios. Effective disease management, minimizing disease activity, and interdisciplinary care are pivotal in attending to women with IBD. The emphasis is placed on the continual assessment of maternal and infant outcomes and an expressed need for further research to enhance the understanding of the ties between IBD and adverse pregnancy outcomes.

Bacterial Extracellular Vesicles (BEVs) generated from the bacteria has high feasibility of intracellular interactions with other cells, can be used as a cargo to deliver any therapeutic substances like monoclonal antibodies, proteins, plasmids, siRNA and small molecules for the treatment of neurodegenerative diseases (NDs). BEVs have a high ability for delivering therapeutic molecules across the blood-brain barrier to treat Alzheimer's Disease (AD) via various mechanisms. In this review, we have sum up in-depth research details of the role and advancement of BEVs in NDs, AD and its Therapeutics. Moreover, details about offensive and defensive functions of BEVs in ND pathogenesis and examine the critical BEV networks in the microbiome-gut-brain axis and their role in neurodegenerative disorders. Additionally determining the roles of BEVs in the neuroimmune system and their interaction with neurodegenerative disorders and exploring the risk factors of BEVs in the autophagy-lysosomal pathway and their possible effects on neurodegenerative disorders are summarised in detail. In conclusion, this review seeks to contribute to a better understanding of the potential function of BEVs in NDs and to identify new therapeutic intervention strategies.

Metabolic-associated fatty liver disease (MAFLD) and diabetic kidney disease (DKD) share various pathophysiological factors, and epidemiological evidence suggests that these two diseases are associated. Albuminuria and the estimated glomerular filtration rate, which are conventional biomarkers of DKD, are reportedly associated with the risk or severity of MAFLD. Recently, novel DKD biomarkers reflecting renal tubular injury have been introduced to complement conventional DKD markers. In this article, we looked at previous studies that showed an association between MAFLD and DKD and also reviewed the significance of DKD biomarkers as predictive risk factors for MAFLD.

Ulcerative colitis (UC) is one of the two disorders known as inflammatory bowel diseases (IBD) along with Crohn’s disease (CD), with complex pathogenesis, requiring costly invasive investigations. Objective: to examine the most recent biomarkers proposed for UC diagnosis; to establish the strategy used to make the differential diagnosis between UC and CD relying on these biomarkers, also adding the benefit of finding new non-invasive tools in managing this condition. The search was performed in a single database (Web of Science) using the specific keywords „ulcerative colitis”, „biomarkers” and „diagnosis” for the last five years. Study eligibility criteria: clinical trials on adults and pediatric patients with ulcerative colitis compared with Crohn’s disease. Results: We selected 57 studies, randomized controlled trials (RCTs) and clinical case series (CCS), summarizing the latest most specific biomarkers in diagnosis of UC. Limitations: we considered RCTs and CCS from one database, limited to the search topics. Our findings indicate a important number of potential biomarkers with diagnostic value, which bring the advantage of a non-invasive method to approach this challenging disorder.

Alzheimer's disease (AD) and Parkinson's disease (PD) are the most common neurodegenerative disorders related to aging. Though several risk factors are shared between these two diseases, the exact relationship between these two diseases is still unknown. In this paper, we analyzed how these diseases relate to each other from a genomics viewpoint. Using an extensive literature search, we accumulated the list of genes from the major genome-wide association (GWAS) studies. However, we found only one gene (HLA-DRB5) reported in these GWAS studies that are common between AD and PD. We also listed all the miRNAs that have been previously reported for AD and PD. Here we found 15 different miRNAs that were reported in both diseases. In order to get better insights, we predicted the gene coexpression network for both AD and PD. Network analysis on these networks show six clusters of genes related to AD and four clusters of genes related to PD.

In the last two decades, the development of high-throughput diagnostic methods and availabil-ity of effective treatments has increased interest in newborn screening for lysosomal storage disorders. However, long-term follow-up experience is needed to clearly identify risks, benefits and challenges. We report our 8-year experience of screening and follow up on about 250,000 neonates screened for four lysosomal storage diseases (Pompe disease, mucopolysaccharidosis type I, Fabry dis-ease, Gaucher disease), using enzyme activity assay by tandem mass spectrometry, and bi-omarker quantification as second tier test. Among the 126 positive newborns (0.051%), 51 infants were confirmed as affected (positive pre-dictive value 40%), with an overall incidence of 1:4,874. Of these, 3 infantile-onset Pompe dis-ease, 2 neonatal-onset Gaucher disease and 4 mucopolysaccharidosis type I patients were imme-diately treated. Furthermore, another four Gaucher disease patients needed treatment in the first years of life. Our study demonstrated the feasibility and effectiveness of newborn screening for lysosomal storage diseases. Early diagnosis and treatment allow the achievement of better patient out-comes. Challenges such as false positive rates, the diagnosis of variants of uncertain significance or late-onset forms, and the lack of treatment for neuronopathic forms, should be addressed.

Health comprises physical, mental and social dimensions whose interactions influence users’ experiences. Health experiences are within the context of environments. These contexts are definitive contributors to experiences – primarily because of the link to social dimensions as human beings - psychological and economic. Therefore, the study aims to investigate health resort users’ psycho-social and socio-economic characteristics to improve their access to quality healthcare. The objectives are identifying the socio-economic characteristics of an inclusive health resort, analysing the psycho-social characteristics of the inclusive health resort user, and analysing the effects of users’ psycho-social and socio-economic characteristics on their access to healthcare. The study employs the mixed research method (qualitative and quantitative). The researchers engaged in a pragmatic research philosophy that underscores positivist and interpretivist paradigms. The data collection instruments include survey questionnaires, an interview guide with a digital recorder, a direct participant observation schedule, field notes and photographs. The data analysis process involves the clustering and categorisation of data and examining concepts and themes. The research findings show a correlation between the users’ socio-economic status and access to quality healthcare in an inclusive health resort. The result further reveals that psycho-social and socio-economic characteristics of health resort users are quality healthcare access predictors. Therefore, the users’ social, psychological, and economic status should play a vital role in the design of an inclusive health resort by all stakeholders.

The study presents an efficient computational investigation on the behaviour of the direct-drive system integrated into the offshore 5MW NREL wind turbine model under demanding aerodynamic loading conditions with the aim of optimising and developing more sustainable key structural components. The research was based on computational simulation packages to verify the use of real-world wind data, the loading conditions on the blade structures through aero-elastic simulation studies, as well as analyse the behaviour of the drive system. Through the application of validated aerodynamic loading conditions, resulting normal forces on the blades structure were obtained and applied to a dedicated simplified model that was also previously validated, to estimate the transferred loads into the powertrain. The adopted methodology allowed for the identification of shaft misalignment induced air-gap eccentricity. The impact of shaft deflections on resulting magnetomotive force was considered by making use of the Maxwell stress distribution expression. By taking into account the resulting loading cases on the generator structure, as well as the inherent typical loads generated by the electrical machine, a procedure including structural parametric and topology optimisation was developed and performed, achieving a rotor mass reduction between 8.5 and 9.6% if compared with the original model.

Depression and anxiety are the most common mental health disorders worldwide. Internet-Delivered Cogni-tive Behaviour Therapy (ICBT) can reduce barriers to care for broad cross sections of the population. How-ever, People of Diverse Ethnocultural Backgrounds (PDEGs) other than White/Caucasian underutilize mental health services and are underrepresented in clinical trials of psychological interventions. To address this research gap, we adapted an evidence-based ICBT program for PDEGs. The current pilot study explores the effectiveness, satisfaction, and engagement in the adapted ICBT by PDEGs (N=41) when benchmarked against a sample of PDEGs (N=134) drawn from a previous non-adapted version of the ICBT program. Inntent-to-treat analyses showed that the adapted ICBT program is effective in reducing anxiety and de-pression symptoms among PDEGs. Large within-group pre-to-post-treatment Cohen’s effect sizes of d = 1.23, 95% CI [0.68, 1.77] and d = 1.24, 95% CI [0.69, 1.79] were found for depression and anxiety, respectively. Further, 81.8% of the PDEGs who received the adapted ICBT program reported high overall satisfaction, 90.9 % reported increased confidence in managing symptoms, and 70.7% of participants completed the ma-jority of the psychoeducational lessons in the ICBT program. No statistically significant differences in clinical outcomes, engagement, and satisfaction were found between the pilot study and benchmark sample. Future directions for ICBT research with PDEGs are described.

The Kingdom of Saudi Arabia (KSA) is known for its high car ownership and usage as well its high GDP per capita. This is combined with low/ or no provision of public transportation (PT) systems, has been resulting in perceptual attitudes of full dependency on private car travel. The level of awareness of the benefits of reducing car use and increasing the travel by more sustainable options, has a great impact on social change and behaviour. The Kingdom is currently progressing towards a new phase of “national transfer” through implementation of strategic and sustainable measures and programs. The city of Riyadh is construction a massive metro-system in Riyadh, that is nearing completion and operation. The public is aware of the national agenda, aware of the newly constructed projects and aware of the needed social change to realize the new vision of the country. This paper aims to assess travel behaviour and attitudes towards public transportation of Saudi travellers’ who are witnessing the new transformation in the Kingdom and who are aware of the new sustainable projects. Depicted from the theory of random utility, a discrete choice model of the intent to use public transportation is calibrated as a function of social and attitudinal factors. An online survey was designed and carried out using social media means; a completed 399 questionnaires have been obtained and studied. The methodology includes examining attitudes and preferences of the participants towards using public transportation options against participants’ socio-economic data. The analysis was carried out using ordinal logistic regression analysis (OLR) which is an efficient technique that is derived from the theory of random utility. The results show a good support for PT; a higher support for public transportation modes, form participants who are young females, lower income groups and the university graduates were reported. The level of support seems higher with the higher level of awareness about the new PT system.

The present paper brings to the fore issues relating to the meaning and construction of ethics in online team communication by exploring the discursive strategies that contribute to the construction of a team’s sense of duty and individual virtuousness. The study relies on a complex toolkit which includes ethnolinguistics, sociolinguistics, discourse and conversation analysis. Data consist in a one-day interaction unit as part of a larger set of real communication exchanges (ca. 34,000) over a time period of six months, observation notes, as well as unstructured interviews. Our empirical analysis has revealed that individual virtuousness and sense of duty are actually interrelated. A virtuous team climate leads team members to share positive perceptions about the team, which in turn increases team commitment. Furthermore, we argue that the blurring of private and professional life not only allows for the enactment of ethic-driven discourse strategies that result in enhanced cooperation and improved team performance but also for high levels of interconnectivity and improved social interaction. The results of the analysis supplement organisational literature based on ethics-centred observations on the effectiveness of virtual work, and show how a discourse-driven approach can provide tools for further theorisations about the practices and the ecology of digital communication.

Determining disability prevalence is an important area for population statistics, especially among young adolescents. The Washington Group on Disability Statistics is one source of reporting disabilities through functional difficulties. However, young adolescents self-reporting this measure is in its infancy. The purpose of this study was to carry out an intra-rater test-retest reliability study on a modified set of items for self-reporting functional difficulties. Young adolescents (n=74; boys=64%; age m=13.7, SD=1.8) completed a self-reported version of the child functioning module in a supervised classroom. The second administration took place two weeks later. Intraclass correlation coefficient (ICC) and Kappa (k) statistics were used to test reliability of the items, and interpretation through Landis &amp; Koch, and Cohen, respectively. The majority of items had substantial or moderate agreement, although there was only fair agreement for self-care (ICC=0.59), concentration (ICC=0.50), and routine (ICC=0.54). Kappa statistics of behaviour were interpreted to be large (k=0.65), and seeing (k=0.49), walking (k=0.49), and speaking (k=0.49) difficulties were moderate. The majority of the items in the self-reported version of the child functioning module can be used in a scale format, although some caution may be required on items of self-care and concentration when used as a dichotomous variable.

This is a theoretical and empirical article. In the first part, an original definition of the cross-border market for cultural services has been developed, based on classic market definitions. The structure and conditions of functioning for this market have also been presented. The next part of the article discusses the supply side of the cross-border market of cultural services for the two twin towns: Cieszyn (Poland) and Český Těšín (Czech Republic). Next, based on the surveys conducted, the participation of residents of both towns in the most important cultural events organised by cultural institutions on both sides of the border was examined.

In the extra-thick coal seams and multi-layered hard roofs, the longwall hydraulic support yielding, coal face spalling, strong deformations of goaf-side entry, and severe ground pressure dynamic events typically occur at the longwall top coal caving longwall faces. Based on the Key strata theory an overburden caving model is proposed here to predict the multilayered hard strata behaviour. The proposed model together with the measured stress changes in coal seam and underground observations in Tongxin coal mine provides a new idea to analyse stress changes in coal and help to minimise rock bursts in the multi-layered hard rock ground. Using the proposed primary Key and the sub-Key strata units the model predicts the formation and instability of the overlying strata that leads to abrupt dynamic changes to the surrounding rock stress. The data obtained from the vertical stress monitoring in the 38 m wide coal pillar located adjacent to the longwall face indicates that the Key strata layers have a significant influence on ground behaviour. Sudden dynamically driven unloading of strata was caused by the first caving of the sub-Key strata while reloading of the vertical stress occurred when the goaf overhang of the sub-Key strata failed. Based on this findings several measures were recommended to minimise the undesirable dynamic occurrences including pre-split of the hard Key strata by blasting and using the energy consumption yielding reinforcement to support the damage prone gate road areas. Use of the numerical modelling simulations was suggested to improve the key theory accuracy.

Despite all scientific efforts and many protracted and expensive clinical trials, no new drug has been approved by FDA for treatment of Alzheimer disease (AD) since 2003. Indeed, more than 200 investigational programs have failed or have been abandoned in the last decade. The most probable explanations for failures of disease-modifying treatments (DMTs) for AD may include late initiation of treatments during the course of AD development, inappropriate drug dosages, erroneous selection of treatment targets, and mainly an inadequate understanding of the complex pathophysiology of AD, which may necessitate combination treatments rather than monotherapy. Clinical trials’ methodological issues have also been criticized. Current drug-development research for AD is aimed to overcome these drawbacks. Preclinical and prodromal AD populations, as well as traditionally investigated populations representing all the clinical stages of AD, are included in recent trials. Systematic use of biomarkers in staging preclinical and prodromal AD and of a single primary outcome in trials of prodromal AD are regularly integrated. The application of amyloid, tau, and neurodegeneration biomarkers, including new biomarkers—such as Tau positron emission tomography, neurofilament light chain (blood and CSF biomarker of axonal degeneration) and neurogranin (CSF biomarker of synaptic functioning)—to clinical trials allows more precise staging of AD. Additionally, use of the Bayesian statistics, modifiable clinical trial designs, and clinical trial simulators enrich the trial methodology. Besides, combination therapy regimens are currently assessed in clinical trials. The abovementioned diagnostic and statistical advances, which have been recently integrated in clinical trials, are consequential to the recent failures of studies of disease-modifying treatments. Their experiential rather than theoretical origins may better equip potentially successful drug-development strategies.

Salmonid alphavirus strain 3 is responsible for outbreaks of pancreas disease in salmon and rainbow trout in Norway. Although the extensive amount of research on SAV3 focused mainly on the heart and pancreas (of clinical importance), tropism and pathogenesis studies of the virus in other salmon tissues are limited. Here, we used a combination of RT-qPCR (Q_nsp1 gene) and in situ hybridization (RNAscope®) to demonstrate the tropism of SAV3 in situ in tissues of Atlantic salmon, employing a challenge model (by cohabitation). In addition, as previous results suggested that pseudobranch may harbor the virus, the change in the expression of different immune genes upon SAV3 infection (RT-qPCR) was focused on the pseudobranch in the current study. In situ hybridization detected SAV3 in the heart, pseudobranch, gills, pyloric caeca, and pancreas after virus infection, with the heart ventricle showing the most extensive infection. Furthermore, the detection of the virus at different adipose tissues associated with the internal organs of the salmon, suggests a specific affinity of SAV3 to adipocyte’s components. The innate immune response to SAV3 in the pseudobranch after infection dominated over the adaptive responses, yet it did not mitigate the infection in that tissue. The early detection of SAV3 in the pseudobranch after infection, along with the persistent low infection over the experimental course, suggests a pivotal role of the pseudobranch in SAV3 pathogenesis in Atlantic salmon.

A synoptic review of plant disease epidemics and outbreaks was made using two complementary approaches. The first approach involved reviewing scientific literature published in 2021, in which quantitative data related to new plant disease epidemics or outbreaks were obtained via surveys or similar methodologies. The second approach involved retrieving new records added in 2021 to the CABI Distribution Database, which contains over a million global geographic records of organisms from over 50,000 species. The literature review retrieved 186 articles, describing studies in 62 categories (pathogen species/species complexes) across >40 host species on 6 continents. Pathogen species with >5 articles were: Bursaphelenchus xylophilus, Candidatus Liberibacter asiaticus, cassava mosaic viruses, citrus tristeza virus, Erwinia amylovora, Fusarium spp. complexes, Fusarium oxysporum f. sp. cubense, Magnaporthe oryzae, maize lethal necrosis co-infecting viruses, Meloidogyne spp. complexes, Pseudomonas syringae pvs, Puccinia striiformis f. sp. tritici, Xylella fastidiosa, and Zymoseptoria tritici. Automated searches of the CABI Distribution Database identified 617 distribution records new in 2021 of 283 plant pathogens. A further manual review of these records confirmed 15 pathogens reported in new locations: apple hammerhead viroid, apple rubbery wood viruses, Aphelenchoides besseyi, Biscogniauxia mediterranea, Ca. Liberibacter asiaticus, citrus tristeza virus, Colletotrichum siamense, cucurbit chlorotic yellows virus, Erwinia rhapontici, Erysiphe corylacearum, Fusarium oxysporum f. sp. cubense Tropical Race 4, Globodera rostochiensis, Nothophoma quercina, potato spindle tuber viroid, and tomato brown rugose fruit virus. Of these, 4 pathogens had at least 25% of all records reported in 2021. We assessed two of these pathogens – tomato brown rugose fruit virus and cucurbit chlorotic yellows virus – to be actively emerging in/spreading to new locations. Although three important pathogens – Ca. Liberibacter asiaticus, citrus tristeza virus and Fusarium oxysporum f. sp. cubense – were represented in the results of both our literature review and our interrogation of the CABI Distribution Database, in general our dual approaches revealed distinct sets of plant disease outbreaks and new records, with little overlap.

This review explores the transformative role of induced pluripotent stem cells (iPSCs) and organoids in advancing neuropathology research. Focused on Alzheimer's disease, epilepsy, Parkinson's disease, and spinal cord injury, iPSCs offer patient-specific disease modeling with regenerative therapy potential. The versatility of iPSCs, their ability to differentiate into the main neuronal cell types, and their integration into three-dimensional organoid models enable the recreation of complex tissues in vitro. Improvement of organoid and iPSCs generation protocols and the selection of appropriate donor cell types are highlighted as crucial steps toward the application of these new technologies to overcome tumorigenic potential and other challenges. iPSCs demonstrate promise in regenerative therapies, as evidenced by successful applications in animal models.

This article provides a thorough overview of biomarkers, pathophysiology, and molecular pathways involved in the transition from acute kidney injury (AKI), acute kidney disease (AKD) to chronic kidney disease (CKD). It categorizes the biomarkers of AKI into stress, damage, and functional markers, highlighting their importance in early detection, prognosis, and clinical application. The pathophysiological mechanisms underlying AKI, AKD, including renal hypoperfusion, sepsis, nephrotoxicity, and immune responses, with the impact on renal injury. In addition, various molecules play pivotal roles in inflammation and hypoxia, triggering maladaptive repair, mitochondrial dysfunction, immune system reactions, and cellular senescence of renal cell. Key signaling pathways, such as Wnt/β-Catenin, TGF-β/SMAD, and Hippo/YAP/TAZ, promote fibrosis and impact renal function. The Renin-Angiotensin-Aldosterone System (RAAS) triggers a cascade leading to renal fibrosis, with aldosterone exacerbating oxidative stress and cellular changes that promote fibrosis. Clinical evidence suggests RAS inhibitors may protect against CKD progression, especially post-AKI, though more extensive trials are needed to confirm their full impact.

There is a pressing need for more precise biomarkers of chronic kidney disease (CKD). Plasma samples from 820 subjects [231 with CKD, 325 with end-stage kidney disease (ESKD) and 264 controls] were analyzed by LC-MS/MS to determine a metabolic profile of 28 aminoacids (AA) and biogenic amines to test their value as markers of CKD risk and progression. The Kynurenine/Tryptophan ratio showed the strongest correlation with estimated glomerular filtration rate values (coefficient=-0.731, P&lt;0.0001). Models created with Orthogonal Partial Least Squares-Discriminant Analysis (OPLS-DA) containing the metabolic signature showed high goodness of fit and predictability for controls/CKD (R2X:0.73;R2Y:0.92;Q2:0.92) and lower for CDK/ESKD (R2X:0.56;R2Y:0.59;Q2:0.55). Based on generated VIP scores, the most relevant markers for segregating samples into control/CKD or CKD/ESKD groups were citrulline (1.67) and tryptophan (1.59), respectively. ROC analysis showed that the addition of the metabolic profile to a model including CKD classic risk factors improved AUC from 86.7% (83.6-89.9) to 100% (100-100) for CKD risk (P&lt;0.0001), and from 63.0% (58.2-67.8) to 96.5% (95.3-97.8) for the risk of progression from CKD to ESKD (P&lt;0.0001). Plasma concentrations of AA and related amines may be useful as diagnostic biomarkers of kidney disease, both for CKD risk and for progression of CKD patients to ESKD.

Circular RNAs (circRNAs) are single-stranded RNA molecules often circularized by backsplicing. Growing evidence implicates circRNAs in the underlying mechanisms of various diseases, such as Alzheimer's and Parkinson's disease (PD) - the first and second most prevalent neurodegenerative disorders. Several circRNAs are associated with brain damage, including circSNCA, circHIPK2, circHIPK3, and circSLC8A1. Gain-of-function and loss-of-function studies on circRNAs have shed light on their roles in the pathobiology of various diseases. Gain-of-function approaches typically employ viral or non-viral vectors that hyperexpress RNA sequences capable of circularizing to form the specific circRNA under investigation. In contrast, loss-of-function studies utilize CRISPR/Cas systems, antisense oligonucleotides (ASOs), or RNAi techniques to knockdown the target circRNA. Given that aberrantly expressed circRNAs have been associated with brain pathologies, a critical question arises: could circRNAs serve as viable targets for neuroprotective treatments? Translating any oligonucleotide-based therapy, including those targeting circRNAs, involves developing adequate brain delivery systems, minimizing off-target effects, and addressing the high costs of treatment. Nonetheless, RNAi-based FDA-approved drugs have entered the market, and circRNAs have attracted significant attention and investment from major pharmaceutical companies. Spanning from bench to bedside, circRNAs present a vast opportunity in biotechnology for oligonucleotide-based therapies designed to slow or even halt the progression of neurodegenerative diseases.

This study investigates how Electronic Livestock Health Recording Systems (ELHRs) facilitates the detection of disease burden and make cluster analysis by applying data analytics tools and techniques. A sample size of 18333 livestock disease cases reported from 2007-2015 by the Ministry of Agriculture of the Federal Democratic of Ethiopia was used for data collection. The results showed that ELHRs are important as livestock disease data preservers, saving costs, and facilitating the extraction of up-to-date and complete information. Euclidean and Manhattan distance performed well at 98%, while cosine distance measurement metrics performed poorly. Finally, with the application of the selected clustering techniques, metrics, tools, and dataset, it has been attempted to successfully detect an optimal number of disease clusters and meet the objectives of the study.

Alzheimer’s disease (AD) and Parkinson’s disease (PD) are the two most common neurodegenerative diseases in elderly. The key histopathological features of these diseases are the presence of abnormal protein aggregates and the progressive and irreversible loss of neurons in specific brain regions. The exact mechanisms underlying the etiopathogenesis of AD or PD remain unknown, but there is extensive evidence indicating that excessive generation of reactive oxygen species (ROS) and reactive nitrogen species (RNS) along with a depleted antioxidant system, mitochondrial dysfunction, and intracellular Ca2+ dyshomeostasis play a vital role in the pathophysiology of these neurological disorders. Due to an improvement in life expectancy, the incidence of age-related neurodegenerative diseases has significantly increased. However, there is no effective protective treatment or therapy available but rather only very limited palliative treatment. Therefore, there is an urgent need for the development of preventive strategies and disease-modifying therapies to treat AD/PD. Because dysregulated Ca2+ metabolism drives oxidative damage and neuropathology in these diseases, the identification or development of compounds capable of restoring Ca2+ homeostasis and signaling may provide a neuroprotective avenue for the treatment of neurodegenerative diseases. In addition, a set of strategies to control mitochondrial Ca2+ homeostasis and signaling has been reported, including decreased Ca2+ uptake through voltage-operated Ca2+ channels (VOCCs). In this article, we review the modulatory effects of several heterocyclic compounds on Ca2+ homeostasis and trafficking, and their ability to regulate compromised mitochondrial function and associated free radical production during the onset and progression of AD or PD. This comprehensive review also describes the chemical synthesis of the heterocycles and summarizes the clinical trial outcomes.

The global population is currently experiencing the impact of the SARS-CoV-2 coronavirus, which has caused the Coronavirus Disease 2019 (COVID-19) pandemic. By our profound comprehension of COVID-19, encompassing the involvement sequence of the respiratory tract, gastrointestinal system, and cardiovascular apparatus, the multiorgan symptoms of this infectious disease have been discerned. Metabolic-associated fatty liver disease (MAFLD) is a pervasive public health concern, intricately linked with metabolic dysregulation and estimated to afflict one-fourth of the global adult population. The burgeoning focus on the association between COVID-19 and metabolic dysfunction-associated fatty liver disease (MAFLD) is justified by the potential role of the latter as a risk factor for both SARS-CoV-2 infection and the subsequent emergence of severe COVID-19 symptoms. Investigations have suggested that changes in both innate and adaptive immune responses among metabolic dysfunction-associated fatty liver disease (MAFLD) patients may play a role in determining the severity of COVID-19. The remarkable similarities observed in the cytokine pathways implicated in both diseases imply the existence of shared mechanisms governing the chronic inflammatory responses characterizing these conditions. The effect of metabolic dysfunction-associated fatty liver disease (MAFLD) on the severity of COVID-19 illness remains uncertain, as indicated by conflicting results in cohort investigations.

The rising global incidence of acute and chronic kidney diseases has increased the demand for renal replacement therapy. This issue, compounded with the limited availability of viable kidneys for transplantation, has propelled the search for alternative strategies to address the growing health and economic burdens associated with these conditions. In the search for such alternatives, significant efforts have been devised to augment the current and primarily supportive management of renal injury with novel regenerative strategies. For example, gene- and cell-based approaches that utilize recombinant peptides/proteins, gene, cell, organoid, and RNAi technologies have shown promising outcomes primarily in experimental models. Supporting research has also been conducted to improve our understanding of the critical aspects that facilitate the development of efficient gene- and cell-based techniques that the complex structure of the kidney has traditionally limited. This manuscript is intended to communicate efforts that have driven the development of such therapies by identifying the vectors and delivery routes needed to drive exogenous transgene incorporation that may support the treatment of acute and chronic kidney diseases.

As a conceptual model of disease mechanisms, a disease map integrates available knowledge and is applied for data interpretation, predictions and hypothesis generation. It is possible to model disease mechanisms on different levels of granularity and adjust the approach to the goals of a particular project. This rich environment together with requirements for high-quality network reconstruction makes it challenging for new curators and groups to be quickly introduced to the development methods. In this review, we offer a step-by-step guide for developing a disease map within its mainstream pipeline that involves using the CellDesigner tool for creating and editing diagrams and the MINERVA Platform for online visualisation and exploration. We also describe how the Neo4j graph database environment can be used for managing and querying efficiently such a resource. For assessing the interoperability and reproducibility we apply FAIR principles.

Human pigmentation has been largely associated with different disease prevalence among populations, but most of these studies are observational and inconclusive. Known to be genetically determined, pigmentary traits have been largely studied by GWAS, mostly in Caucasian ancestry cohorts from North Europe, identifying robustly, several loci involved in many of the pigmentary traits. Here, we conduct a detailed analysis of 13 pigmentary-related traits in a South European cohort of Caucasian ancestry (n=20,000). We observed fair phototype strongly associated with non-melanoma skin cancer and other dermatoses and confirmed by PRS-approach the shared genetic basis with skin and eye diseases, such as melanoma (OR=0.95), non-melanoma skin cancer (OR=0.93), basal cell carcinoma (OR=0.97) and darker phototype with vitiligo (OR=1.02), and cataracts (OR=1.04). Detailed genetic analyses revealed 37 risk loci associated with 10 out of 13 analyzed traits, and 16 fine-mapped genes significantly associated with at least two pigmentary traits. Some of them widely reported, such as MC1R, HERC2, OCA2, TYR, TYRP1, SLC45A2, and unveiling three new candidates RP11-1084J3.4, C1QTNF3 and C17orf112, not reported in GWAS Catalog. These results highlight the importance of phototype assessment as a genetic proxy of skin functionality when evaluating disease screening in mixed populations.

Humans are a vision-dominated species, and what we see depends on where we look. Therefore, eye movements (EM) are essential to our interactions with the environment, and experimental findings show EM is affected in neurodegenerative disorders (ND). It could be a reason for some cognitive and movement disorders in ND. Therefore, we aim to determine if changes in EM-evoked responses can tell us about ND, such as Alzheimer’s (AD) and Parkinson’s Disease (PD) progression in different stages. In the present review, we have analyzed the results of neurological, psychological, and EM (saccades, antisaccades, pursuit) tests to predict disease progression with Machine Learning (ML) methods. Described predictive algorithms are using various approaches, including Granular Computing, Naive Bayes, Decision Trees/Tables, Logistic Regression, C-/LinearSVC, KNC, and Random Forest. We demonstrated that EM is a robust biomarker for assessing symptom progression in PD and AD. There are also navigation problems in 3D space in both diseases. Consequently, we investigated EM experiments in the virtual space and how they may help find neurodegeneration-related brain changes. In conclusion: EM parameters with clinical symptoms are powerful precision instruments that, in addition to predictions of ND progression with the help of ML, could be used to indicate the different preclinical stages of both diseases.

Background: Crohn’s and Ulcerative Colitis Questionnaire-32 (CUCQ-32) is a validated questionnaire to measure the quality of life (QoL) in inflammatory bowel disease (IBD). However, it does not have stoma specific questions and can be lengthy. This study aimed to validate a subset of the CUCQ-32 that would be suitable for patients with a stoma. Methods: Baseline data were collected from a cohort of patients with acute ulcerative colitis who were participating in the CONSTRUCT multi-centre clinical trial. A subset of the CUCQ-32 questions was selected by stepwise regression. Further validation was examined using data from the UK IBD biological therapies audit. Construct validity was carried out using the EuroQol 5 dimensions (EQ5D) questionnaire, Simple Clinical Colitis Activity Index (SCCAI) and the Harvey-Bradshaw Index (HBI). Literature review and an expert focus group identified supplementary questions to cover patients with a stoma. Test-retest analysis was done during the patients’ second follow up visits. Results: Using the data from 124 patients, a short version questionnaire (CUCQ-12) was developed. Further validation using data from 484 patients with IBD as part of the UK IBD biological therapies audit. Using the data from 61 patients with a stoma, we identified 5 stoma specific questions for the CUCQ-12+. The CUCQ-12+ demonstrated excellent internal consistency (Cronbach’s α= 0.86); established effective reproducibility (intra-class correlation coefficient= 0.74); correlated well with the EQ5D (r= - 0.48), HBI (r= 0.45) and SCCAI (r= 0.43); and represented good responsiveness statistics (>0.5). Conclusions: CUCQ-12+ is a valid and reliable QoL measure that can be used for all patients with IBD in clinical practice including patients with a stoma.

Mitochondrial dysfunctions remained a pivotal mechanism in manifold neurodegenerative diseases. Mitochondrial homeostasis within the cell is an essential aspect of cell biology. Mitochondria which is also known as the power-generating set of the cell, have a dominant role in several processes associated with the genomic integrity and cellular equilibrium maintenance. They are involved in maintaining optimal cells functioning and guidance from possible DNA damage which could lead to mutations and onset of diseases. Conversely, system perturbations which could be due to environmental factors or senescence induce changes in the physiological balance and result in the mitochondrial functions impairment. The focal point of this review focuses on mitochondrial dysfunction as a significant condition in the onset of neuronal disintegration. We explain the pathways associated with the dysfunction of the mitochondria which are common amongst the most recurring neurodegenerative diseases including Alzheimers and Parkinsons disease. Do mitochondrial dysfunctions represent an early event in causing a shift towards neuropathological processes?

Aleutian mink disease virus (AMDV) is known to cause the most significant disease in the mink industry. It is globally widespread and manifested as a deadly plasmacytosis and hyperglobulinemia. So far, measures to control viral spread have been limited to manual serological testing for AMDV-positive mink. Further, due to the persistent nature of this virus, attempts to eradicate Aleutian disease (AD) have largely failed. Therefore, effective strategies to control viral spread are of crucial importance for wildlife protection. One potentially key tool in the fight against this disease is by immunization of mink against AMDV. Throughout many years, several researchers have tried to develop AMDV vaccines and demonstrated varying degrees of protection in mink by those vaccines. Despite these attempts, there are currently no vaccines available against AMDV, allowing the continuation of the spread of Aleutian disease. Herein, we summarize previous AMDV immunization attempts in mink as well as other preventative measures with the purpose to shed light on future studies designing such a potentially crucial preventative tool against Aleutian disease.

The control of Porcine Reproductive and Respiratory Syndrome (PRRS) is still a major issue worldwide in the pig farming sector. Despite extensive research efforts and the practical experience gained so far, the syndrome still heavily affects farmed pigs worldwide and challenges established beliefs in veterinary virology and immunology. The clinical and economic repercussions of PRRS are based on concomitant, additive features of virus pathogenicity, host susceptibility and influence of environmental, microbial and non-microbial stressors. This makes a case for integrated, multi-disciplinary research efforts in which the three types of contributing factors are critically evaluated toward the development of successful disease control strategies. These could be definitely eased by the definition of reliable markers of disease risk and virus pathogenicity. As for the host’s susceptibility to PRRSV infection and disease onset, the roles of both innate and adaptive immune responses are still ill-defined. In particular, the overt discrepancy between passive and active immunity and the uncertain role of adaptive immunity vis-à-vis an established PRRSV infection should prompt the scientific community to the development of novel research schemes, in which apparently diverging and contradictory findings could be reconciled, and eventually brought to a satisfactory conceptual framework.

Neurological disorders, such as amyotrophic lateral sclerosis, Parkinson’s disease, and Alzheimer’s disease, are commonly associated with persistent neuro-inflammation, and there is an urgent need to discover new therapeutic agents that may target the various pathways involved in neurodegeneration. In this study, we investigated the therapeutic potential of folecitin, a flavonoid isolated from Hypericum oblongifolium, against lipopolysaccharide (LPS)-induced oxidative stress associated with neurodegeneration, amyloidogenic Aβ production pathway, and memory dysfunction in mice. LPS was administered i.p. at 250 µg/kg/day for 3 weeks, followed by the administration of folecitin at a dose of 30 mg/kg/day for the last two weeks. A Western blot technique was used to assess the expression of different proteins involved in oxidative stress, neurodegeneration, and neuronal synapse. Results indicated that folecitin significantly reduced LPS-induced apoptotic neurodegeneration, including the expression of BAX, Caspase-3, and PARP-1 proteins, inhibited BACE1, and the amyloidogenic Aβ production pathway. Folecitin improved both pre- and post-neuronal synapse, as well as memory dysfunction. Furthermore, folecitin significantly activated endogenous antioxidant proteins such as Nrf-2 and HO-1 via stimulating the phosphorylation of Akt proteins. These findings suggest that folecitin may be a suitable lead to design new drugs for neurotoxin-triggered neurodegenerative disorders.

Crohn’s disease is an inflammatory bowel disease whose prevalence is increasing worldwide. Among medical strategies, the dietary therapy with exclusive enteral nutrition is recommended as first line option, at least for children, because it induces clinical remission and mucosal healing. Modulen®, a polymeric TGF-β2 enriched formula, has a good palatability and is widely used. For the first time in the literature, this review outlines and discusses the clinical outcomes obtained with this therapy, as well as the potential mechanisms of action of its compounds. It can be explained by its TGF-β2 content but also by its protein and lipid composition. Further well-designed studies are required to improve our knowledge and to optimize therapeutic strategies.

Latest evidence revealed a possible association between Parkinson’s disease (PD) and periodontitis. We explored the causal relationship of this association through two-sample Mendelian randomization (MR) in European ancestry populations. To this end, we used openly accessible data of genome-wide association studies (GWAS) on PD and periodontitis. As instrumental variables for periodontitis, seventeen single-nucleotide polymorphisms (SNPs) from a GWAS of periodontitis (1817 periodontitis cases vs. 2215 controls) and forty-five SNPs from a GWAS of PD (20,184 cases and 397,324 controls). Eight non-overlapping SNPs of periodontitis from an additional GWAS assisted in the validation of association being studied. Multiple approaches of MR were carried-out. There was no evidence of genetic liability of periodontitis being associated with a higher risk of PD (B= -0.0003, Standard Error [SE] 0.0003, P = 0.26). The eight independent SNPs (B= -0.0000, SE 0.0001, P = 0.99) validated this outcome. We found no association of genetically primed PD towards periodontitis (B= -0.0001, SE 0.0001, P = 0.19). This MR study found no conclusive evidence to support a bidirectional causal genetic liability between PD and periodontitis. Further GWAS studies are needed to confirm the consistency of these results.

Tomato (Solanum lycopersicum L.) is a valuable horticultural crop grown and consumed worldwide. Optimum production is hindered by several factors of which Verticillium dahliae, the cause of Verticillium wilt, is one of the major biological constraints in temperate production regions. V. dahliae is difficult to manage because it is a vascular pathogen, has a broad host range and worldwide distribution, and can persist in soil for years. Understanding the pathogen virulence and genetic diversity, host resistance, and plant-pathogen interactions can ultimately inform the development of integrated strategies to manage the disease. In recent years, considerable research has focused on providing new insight into these processes as well as the development and integration of environment-friendly management approaches. In this review, we discuss and summarize the recent findings on the race and population structure of V. dahliae; pathogenicity factors; host genes, proteins, and enzymes involved in defense; the emergent management strategies, and recent approaches to managing Verticillium wilt in tomatoes.

Recent studies supported a clinical association between Parkinson’s Disease (PD) and periodontitis. Hence, investigating possible protein interactions between these two conditions is of interest. In this study, we conducted a protein-protein network interaction analysis with recognized genes encoding proteins for PD and periodontitis. Genes of interest were collected via GWAS database. Then, we conducted a protein interaction analysis using STRING database, with a highest confidence cut-off of 0.9. Our protein network casted a comprehensive analysis of potential protein-protein interactions between PD and periodontitis. This analysis may underpin valuable information for new candidate molecular mechanisms between PD and periodontitis and may serve new potential targets for research purposes. These results should be carefully interpreted giving the limitations of this approach.

Rice is consumed as a staple food by majority of the people in the world and failure in rice crop, due to any reason, poses a severe threat of starvation. Rice blast, caused by a fungus blast has been ranked among the most important plant diseases. It is by far the most threatening disease of ric crop and it is found wherever rice is grown. All of the rice blast disease management strategies that have been employed have limited success and rice blast has never been eliminated from a region in which rice is grown. Hence there is need to look for the best remedy in terms of effectiveness and organic nature of the method etc. This study was aimed to determine the plant growth promoting and biopesticidal effects of bioactive components present in a mixture of Piper caninum and Piper betle var. Nigra leaf extracts. . The extracts were applied in the field to determine their inhibition effects against blast disease, growth and yield improvement.. Extract of both the plants promoted plant growth and exhibited antifungal activity against rice blast fungus, Pyricularia oryzae. However the synergistic effect of the mixture of the two extracts exhibited greater effects than an effect of a single extract. . All treatments reduced the intensity of blast disease on week 15 with disease intensity by 7.90%. The extracts could increase plant height, the numbers of tillers, number of leaves, number of grains per panicle number of heads per panicle, and the full-grain weight hill.. The highest potential yield (t/ha) was observed in the 2% extract treatment, and all treatment results significantly differed from that of the control. The potential grain yield was 3.23 t/ha in the control, while that in the treatment ranged from 3.81 t/ha to 5.61 t/ha. The high grain yield observed with the treatment was caused by the low intensity of blast disease.

Introduction: Lyme disease is a tickborne illness that generates controversy among medical providers and researchers. One of the key topics of debate is the existence of persistent infection with the Lyme spirochete, Borrelia burgdorferi, in patients who have been treated with recommended doses of antibiotics yet remain symptomatic. Persistent spirochetal infection despite antibiotic therapy has recently been demonstrated in non-human primates. We present evidence of persistent Borrelia infection despite antibiotic therapy in patients with ongoing Lyme disease symptoms. Materials & Methods: In this pilot study, culture of body fluids and tissues was performed in a randomly selected group of 12 patients with persistent Lyme disease symptoms who had been treated or who were being treated with antibiotics. Cultures were also performed on a group of 10 control subjects without Lyme disease. The cultures were subjected to corroborative microscopic, histopathological and molecular testing for Borrelia organisms in four independent laboratories in a blinded manner. Results: Motile spirochetes identified histopathologically as Borrelia were detected in culture specimens, and these spirochetes were genetically identified as Borrelia burgdorferi by three distinct polymerase chain reaction (PCR) methods. Spirochetes identified as Borrelia burgdorferi were cultured from the blood of seven subjects, from the genital secretions of ten subjects, and from a skin lesion of one subject. Cultures from control subjects without Lyme disease were negative for Borrelia using these methods. Conclusions: Using multiple corroborative detection methods, we showed that patients with persistent Lyme disease symptoms may have ongoing spirochetal infection despite antibiotic treatment, similar to findings in non-human primates. The optimal treatment for persistent Borrelia infection remains to be determined.

Healthy life style is associated with decreased risk of chronic kidney disease (CKD) and mortality in the general population. However, there is no definitive evidence on the benefits of physical activity and other health-related behaviors in the early-stage CKD. This study aimed to explore the association between health-related behaviors and end-stage renal disease (ESRD) and mortality in the early stages of CKD. The National Health Insurance Service (NHIS) database from January 1st, 2009 to December 31st, 2016 was used to screen 83,470 subjects with early stage CKD. Cox proportional hazard regression analysis was used to evaluate the association between health-related behaviors and ESRD and death. Kaplan-Meier curves for mortality and ESRD were plotted according to the physical activity, smoking status and alcohol consumption pattern. Risk of death decreased significantly in subjects who engaged in sufficient physical activity (adjusted Hazard Ratio (HR) 0.73; 95% CI: 0.64-0.83; p < 0.001). Risk of ESRD and death increased significantly in the current smoker with adjusted HR of 1.44 (95% CI: 1.06-1.95; p < 0.02) and 1.61 (95% CI: 1.44-1.80; p < 0.001) respectively. Therefore, systematic interventions to encourage physical activity and smoking cessation need to be actively considered in the early stages of CKD.

There is an anecdotal impression that teenage patients report exaggerated postoperative pain scores that do not correlate with their actual level of pain. Nurse and parental perception of teenagers' pain can be complemented by knowledge of patient pain behavior, pain catastrophizing thoughts, anxiety, and mood level. Two hundred two patients completed the study: 56.4% female, 89.6% White, 5.4% Black, and 5% other race. Patient ages ranged from 11 to 17 years (mean = 13.8, SD = 1.9). The patient, the parent, and the nurse completed multiple questionnaires on day one after laparoscopic surgery to assess patient pain. Teenagers and parents (r=0.56) have a high level of agreement, and teenagers and nurses (r=0.47) have a moderate level of agreement on pain scores (p &lt;0.05). The correlation between patient APBQ (Adolescent Pain Behavior Questionnaire) and teenager VAS (Visual Analog Scale ) and between nurse APBQ and teenager VAS, while statistically significant (p &lt; 0.05), is weaker (r range = 0.14-0.17). There is a moderate correlation between teenagers' pain scores and their psychological assessments of anxiety, catastrophic thoughts, and mood (r range= 0.26 – 0.39; p &lt;0.05). A multi-modal evaluation of postoperative pain can be more informative than only assessing self-reported pain scores.

With the rise of internet technology and the growth of mobile communications, the global economy has undergone a significant transformation, shifting towards digital and soft markets. As a result, great efforts have been made to establish virtual marketplaces that provide customers with an exceptional shopping experience. One crucial aspect of this new paradigm is marketing, which has led to the emergence of a new stage known as E-marketing. In E-marketing, understanding customer behavior is of utmost importance. Marketing teams and companies are eager to gain insights into how different customer segments react to their products. Marketing strategies are now developed based on customer information such as financial status, location, age, gender, and more. As a result, the abundance of customer data generated by these new commerce technologies has surpassed the capabilities of traditional data analysis methods. To extract valuable knowledge from this vast amount of data, data mining technologies have come into play. Techniques such as clustering, classification, and prediction are utilized to mine marketing data and uncover hidden patterns and trends. The impact of data mining on E-marketing has been the subject of analysis in this study. A questionnaire-based review was conducted to collect the necessary data, which was then analyzed using SPSS 23 software. The study's results demonstrate that data mining can significantly enhance the performance of E-marketing by providing intelligent and efficient predictions of customer behaviour. Moreover, this technology offers similar advantages for end-customers as well. By leveraging the power of data mining, companies can gain valuable insights, tailor their marketing efforts, and ultimately provide better products and services to their customers in the digital marketplace.

The availability of sufficient amounts of form I of benzocaine has led to the investigation of its phase relationships with the other two existing forms II and III using adiabatic calorimetry, powder X-ray diffraction, and high-pressure differential thermal analysis. The latter two forms were known to have an enantiotropic phase relationship with form III stable at low-temperature and high-pressure, while form II is stable at room temperature. Using adiabatic calorimetry data, it can be concluded, that form I is the stable low-temperature, high-pressure form, which also happens to be stable at room temperature; however, form II, due to its persistence at room temperature, is still the most convenient polymorph to use in formulations. Form III presents a case of overall monotropy and does not possess any stability domain in the pressure-temperature phase diagram. Heat capacity data for benzocaine have been obtained by adiabatic calorimetry from 11 K up to 369 K above its melting point, which can be used to compare to results from in-silico crystal structure prediction.

In this paper, a new method is proposed to detect traffic regulations at intersections using GPS traces. The knowledge of traffic rules of regulated locations can help various location-based applications in the context of Smart Cities, such as the accurate estimation of travel time and fuel consumption from a starting point to a destination. Traffic regulations as map features, however, are surprisingly still largely absent from maps, although they do affect traffic flow which in turn affects vehicle idling time at intersections, fuel consumption, CO_2 emissions and arrival time. In addition, mapping them using surveying equipment is costly and any update process has severe time constraints. This fact is precisely the motivation for this study. Therefore, its objective is to propose an automatic, fast, scalable and inexpensive way to identify the type of intersection control (e.g. traffic lights, stop signs). A new method based on summarizing the collective behavior of vehicles crossing intersections is proposed. A modification of a well-known clustering algorithm for detecting stopping and decelerating events is presented. These detected events are then used to categorize vehicle crossing of intersections into four possible traffic categories (p1: free flow, p2: deceleration without stopping events, p3: only one stopping event, p4: more than one stopping event). The percentages of crossings of each class per junction arm, together with other speed/stop/deceleration features, extracted from trajectories, are then used as features to classify the junction arms according to their traffic control type dynamic model). The classification results of the dynamic model are compared with those of the static model, where the classification features are extracted from OpenStreetMap. Finally, a hybrid model is also tested, where a combination of dynamic and static features is used, which outperforms the other two models. For each of the three models, two variants of the feature vector are tested: one where only features associated with a single junction arm are used (one-arm model) and another where features also from neighbouring junction arms of the same junction are used to classify an arm (all-arm model). The methodology was tested on three datasets and the results show that all-arm models perform better than single-arm models with an accuracy of 94\% to 97\%.

A more sustainable society and economy also implies a more sustainable behavior in the consumption of financial products. A possible change in focus can come from the demand side, so that more sustainable consumption of financial products have to go hand to hand with financial literacy. However, financial literacy, potential favoring of this sustainable behavior, is far from reaching an international consensus about its definition, object and scope. Two objectives are analyzed; the different interpretations of financial literacy in the academic literature, as well as its evolution and how, in what context and with what other concepts the term is used in social networks. Scientometric techniques and content analysis have been used to carry out a systematic review of literature and also NLP to analyze the comments on Social Networks. Critical moments are identified in the definition of financial literacy. Also ten sentiments are analyzed in social networks in wich positivity, trust, and anticipation predominate. Greater attention to this issue is necessary both from the private initiative and from public policies, so that financial literacy is an effective tool for a more sustainable behavior by consumers. Finally, a new definition is proposed based on our findings.

This research focuses on the customer orientation of insurance brokers, whose activity is regulated by the Law of 26/2006 of July 17 on the mediation of private insurances and reinsurances. The goal is to ascertain whether the intermediation inherent in the insurance broker’s activity, which implies a customer-oriented service, entails a positive behaviour that transcends the immediate environment, reaching society. This study presents a comparative analysis between the insurance brokerage society, characterised by providing a personalised customer service, and banks’ advisory services on insurance. To this end, we study the evolution of the total volume of business and new production, compared for a portfolio of insurance products. The results presented in this research suggest that the customer values the advisory service provided by the broker. However, for a particular business segment in standardised insurance products and products related to banking assets, customers are more likely to resort to the bank’s services. In addition, the results indicate that the commission percentages applied by the entities operating in the banking insurance channel exceed those perceived by the insurance broker. With all this, intermediation in the development of the insurer’s activity can entail an ethical and social behaviour that involves customer-orientation and, possibly, social service, which does not always benefit the insurer.

The residential built form, including open space, provides the physical environment for social interaction. Understanding urban open space, including semi-public and public domains, through the lens of physical accessibility and visual permeability can potentially facilitate the building of a sense of community contributing to a better quality of life. Using an inner-city suburb in Perth, Western Australia as a case study, this research explores the importance of physical accessibility patterns and visual permeability for socialising in semi-public and public domains, such as the front yard and the residential streets. It argues that maintaining a balance between public and private inter-relationship in inner city residential neighbourhoods is important for creating and maintaining a sense of community.

A reduction of melatonin function contributes to the acceleration of Alzheimer's disease (AD), and understanding molecular processes of melatonin-related signaling is critical for intervention of AD progression. Recently, we synthesized and tested a series of melatonin derivates with donepezil fragments in silico and in vitro. In this study, one of the most potent compounds, 3c, was studied in an in vivo rat model of pinealectomy (pin) and subsequent icvAβ1-42 infusion. Melatonin was used as a referent drug. The treatment with melatonin and 3c (10 mg/kg, i.p. for 14 days) exerted a beneficial effect on memory decline and concomitant rise of Aβ1-42 and pTAU in the hippocampus in the pin + icvAβ1-42 rats. Melatonin supplementation facilitated the non-amyloidogenic signaling via a non-receptor (histone deacetylase sirtuin 1, SIRT1) and receptor-related signaling (MT/ERK/CREB). The hybrid 3c derivate up-regulated the MT1A and MT2B receptors, pERK and pCREB. Our findings strongly support the hypothesis that melatonin-related derivates may become a promising drug candidate in AD therapy.

Patients with neurodegenerative diseases (NDDs) are rapidly increasing all over the world. Alzheimer’s disease (AD), Parkinson’s disease, Huntington’s disease (HD), frontotemporal lobar degeneration (FTLD) and many other diseases are classified as NDDs, however, no therapeutic drugs have been developed against NDDs yet. As common phenomenon, protein oligomers and aggregates (inclusion bodies) are formed in neurons, and they trigger neuronal cell death and/or axonal degeneration. We have investigated the mechanisms of NDDs, and discovered several chemicals and peptides have potential to cure NDDs. Here, we show phorbol 12-myristate 13-acetate (PMA) significantly inhibits aggregate formation and promotes neurite regeneration in human neuronal cell culture model of NDDs, FTLD and AD. We expressed R406W mutant tau protein found in FTLD patients in human neuroblastoma SH-SY5Y cells as FTLD cell culture model. These FTLD neuronal cells showed intracellular aggregate formation and impaired neurite growth. Addition of PMA to culture medium 60% suppressed aggregate formation. PMA also enhanced neurite growth to the normal level at nanomolar concentration. We cultured SH-SY5Y cells in the medium containing -amyloid (1-42) as AD cell culture model. In these cells, neurite growth was limited to less than 50% of controls by the treatment of -amyloid (1-42). Surprisingly, addition of PMA increased the number of cells with >10-fold neurite extension to seven times even in -amyloid (1-42) contained medium. Also, PMA increased the expression of several genes and proteins important for cell survival in both cell culture models. These results suggest PMA has unexpected potential for the drug development against NDDs.

Age is the primary risk factor for neurodegenerative diseases such as Alzheimer’s and Huntington’s disease. Alzheimer’s disease is the most common form of dementia and a leading cause of death in the elderly population of the United States. No effective treatments for these diseases currently exist. Identifying effective treatments for Alzheimer’s, Huntington’s, and other neurodegenerative diseases is a major current focus of national scientific resources, and there is a critical need for novel therapeutic strategies. Here we investigate the potential for targeting the kynurenine pathway metabolite 3-hydroxyanthranilic acid (3HAA) using Caenorhabditis elegans expressing amyloid-beta or a polyglutamine peptide in body wall muscle, modeling proteotoxicity in Alzheimer’s and Huntington’s disease-related, respectively. We show that knocking down the enzyme that degrades 3HAA, 3HAA dioxygenase (HAAO) delays age-associated paralysis in both models. This effect on paralysis was independent of protein aggregation in the polyglutamine model. We also show that the mechanism of protection against proteotoxicity from HAAO knockdown is mimicked by 3HAA supplementation, supporting elevated 3HAA as the mediating event liking HAAO knockdown to delayed paralysis. This work demonstrates potential for 3HAA as a targeted therapeutic in neurodegenerative disease, though the mechanism is yet to be explored.

Myotonic dystrophy is a hereditary disorder with systemic involvement. The Italian Neuro-Cardiology Network (INCN-RNC) is a unique collaborative experience involving neurology units combined with cardio-arrhythmology units. The INCN facilitates the creation of integrated neuro-cardiac teams in Neuromuscular Disease Centers for the management of cardiovascular involvement in the treatment of MD1.

Disease detection and prediction have been one of the most frequent uses of machine learning models in the last decade, and Parkinson's disease is no exception. It is common for people in their old age to have one form of disease or another depending on the circumstances in which they find themselves. This study analyzed and evaluated various supervised machine learning models to detect the presence of Parkinson's disease in elderly individuals. An extreme gradient boosting model, along with other models, such as naïve Bayes, random forest, K-nearest neighbor, and support vector machine (SVM), was implemented to determine the best outcome. The extreme gradient boosting (XGBoost) model is a powerful boosting machine learning technique, particularly in terms of speed and accuracy. The results showed that the XGBoost model, which is an optimized version of the other boosting models, is capable of projecting the presence of Parkinson's disease with very high accuracy compared to other algorithms. The implemented classification algorithm extreme gradient boosting method achieved approximately 98 % accuracy, 97.5 % precision, 100.0 % recall, and 98.7% f1-score which are high compared with the results found in the existing literature.

TAU is the main disease driver in Alzheimer’s and many other sporadic and genetic tauopathies. TAU is differently spliced, the role of individual splice-isoforms unclear. Murine Mapt-KO mice are healthy, and protected from Alzheimer’s, but no such case has been reported in humans. Using gnomad database, we here demonstrate that the only isoform expressed during fetal human brain development is intolerant to mutation, while other brain and peripheral nervous system TAU isoforms are dispensable. With TAU targeted therapies for Alzheimer’s and other tauopathies on the rise, we caution that TAU is essential human brain development.

Chronic non-bacterial osteomyelitis (CNO), also known as chronic recurrent multifocal osteomyelitis (CRMO), is a rare autoinflammatory bone disease primarily affecting children and adolescents. This review presents a comprehensive analysis of the intricate relationship between CNO and inflammatory bowel disease (IBD), shedding light on shared pathophysiological mechanisms and clinical management. A thorough literature review was conducted, encompassing 24 case reports involving 40 patients. The demographic distribution of patients revealed a near-equal gender ratio, with a median age of diagnosis at 12 years. The diagnosis patterns showed a higher proportion of CNO as the initial diagnosis, while Crohn's disease was more prevalent than ulcerative colitis. The time interval between the clinical presentations varied, ranging from simultaneous detection to a substantial 15-year gap. Treatment modalities included non-steroidal anti-inflammatory drugs (NSAIDs), steroids, aminosalicylates, and biologic agents, such as infliximab, often overlapping in their use, suggesting shared pathophysiological pathways. Both conditions displayed systemic manifestations, and patients often responded well to immunosuppressive medications. The pathophysiology of CNO involves genetic predisposition, cytokine dysregulation, and osteoclast activation. Dysregulated innate immunity results in immune cell infiltration into bones, causing sterile bone lesions. Notably, emerging evidence hints at a potential link between the microbiome and CNO. In contrast, IBD results from imbalanced mucosal immune responses to the intestinal microbiota. Polymorphisms in the promotor region of IL-10, common cytokines, immune cells, and genetic markers indicate shared immunological and genetic factors between CNO and IBD. Both conditions also involve extraintestinal symptoms. This analysis underscores the need for clinical awareness of the co-occurrence of CNO and IBD, especially among pediatric patients. A deepened understanding of the connections between these seemingly distinct diseases could lead to more effective management and improved patient outcomes.