The risk classification of barrier lake is the key to conducting emergency treatment in a scientific manner. Such difficulties are faced as short time for risk evaluation, complex evaluation indicators, difficulty in obtaining information quickly and quantifying index weights. Based on this, this paper constructs a quantitative risk classification model for barrier lakes based on D-AHP. On the basis of studies on nearly 100 cases of barrier lakes, an 8-factor evaluation index system and quantitative classification are proposed. The methods of rapid calculation of reservoir capacity curve of barrier lake and intelligent identification of particles on the surface of barrier body were developed, which realized the rapid acquisition of 8-factor evaluation index information in emergency environment. The D-AHP method dealt with inconsistent weight assignment to evaluation factors by experts, which helped achieve weight quantification of 8 factors. The risk assessment on15 barrier lakes such as Tangjiashan barrier lake show that the conclusion drawn with risk classification method proposed in this paper is basically consistent with that of the traditional table-lookup method. However, the table-lookup method ignores cumulative loss’s impacts on the risk level of barrier lakes, and considers the extremely severe loss of barrier lakes as a sufficient condition for the evaluation level to be grade I, and thus a deviation in the evaluation. The risk classification method proposed in this paper is more reasonable and reliable.

German noise action plans aim to reduce negative health outcomes from noise exposure and identify quiet areas free of noise pollution. Quiet area identification in German noise action plans is based primarily on noise mapping and spatial analysis and not empirical or qualitative data about acoustic environments, thus leaving a gap in the understanding of the quality of formally recognized quiet areas in noise action plans. This work presents a comparative empirical case study in Dortmund, Germany, with the aim to describe the diurnal dB(A) and biophonic properties of quiet areas versus noise 'hot spots'. Sound observations were collected (n=282,764) in five different natural or recreational land use patch types larger than four acres within 33 proposed quiet areas in Dortmund (n=70) and 23 noise hot spots between April 27^th, 2022 and March 2^nd, 2023. We find that quiet areas are on average more than 20 dB(A) quieter than noise hot spots almost every hour of the day. Forests, managed tree stands, cemeteries, and agriculture diel patterns are dominated by dawn dusk chorus in spring and summer, whereas sport and recreation as well as noise hot spots are dominated by traffic and human noise. A novel composite biophony mapping procedure is presented that finds distinct temporal distribution of biophony in forested and agriculture peri-urban locations positively associated with patch size, distance away from LDEN > 55, proximity to water, and the number of vegetation layers in the plant community. Anthrophony distribution dominates urban land uses in all hours of the day, but expands during day and evening and contracts at night and in dusk hours. The procedures presented here illustrate how qualitative information regarding quiet areas can be integrated into German noise action planning.

Background: Early diagnosis of postoperative complications is an urgent task, allowing timely prescribing of appropriate therapy and reducing the cost of patient treatment. Prognostic models based on various data could help in the early diagnosis of postoperative complications after cardiac surgery. Objectives: The purpose of the study was to determine whether an integrated approach based on clinical data along with metabolites and biomarkers had greater predictive value than the models built on less data. Methods: The study included patients (n=62) admitted for planned cardiac surgery (coronary artery bypass grafting with cardiopulmonary bypass), who were retrospectively divided into two groups depending on the presence (n=26) or absence (n=36) of postoperative complications of all types. Clinical and laboratory data on the first day after surgery were analyzed. Additionally, patients' blood samples were collected before and on the first day after surgery to determine biomarkers (interleukin-6, procalcitonin, NT-proBNP, high-sensitivity troponin T) and metabolites (8 aromatic and 2 dicarboxylic acids were detected using gas chromatography-mass spectrometry). Results: Patients before surgery, compared with healthy donors, differed in the concentration of metabolites (p < 0.05), and had concentrations of a number of biomarkers exceeding the corresponding reference values. Multivariate PLS-DA models, predicting the presence or absence of postoperative complications, were built using clinical data (ROC-AUC=0.71), concentrations of metabolites and biomarkers (ROC-AUC=0.60), and the entire data set (ROC-AUC=0.75). For comparison we built univariate models using the EuroScore2 (ROC-AUC=0.59) and SOFA (ROC-AUC=0.76) scales; concentrations of lactate (ROC-AUC=0.71), the dynamic changes of 4-hydroxyphenyllactic acid (ROC-AUC=0.69), and the sum of three sepsis-associated metabolites (ROC-AUC=0.70). The proposed complex model using entire data set was comparable to the SOFA scale, which confirms the expediency of searching for new predictive models based on a variety of factors.

This study was conducted to identify the actual degree of underdevelopment and spatial characteristics of rural areas in Korea, which are expected to face extinction due to population decline and aging. For this purpose, the spatial scope was set to Eup and Myeon areas classified as rural regions. To assess the degree of underdevelopment, previous studies were reviewed and analyzed to develop a comprehensive underdevelopment index, which was then applied to Eup and Myeon areas to classify them into growth regions, general regions, and depressed regions. Mapping the classified regions revealed that both growth and general regions were concentrated in the metropolitan area and southeastern regions, where Korea's population and resources are densely clustered. In contrast, depressed regions were found primarily in areas where agriculture is the main industry and in regions with unfavorable geographical conditions. This study is significant as it covers the entire nation of Korea, providing a method for identifying depressed regions and highlighting the regions that are developing. The findings can serve as fundamental data for the development of policies to address population decline in the future.

Extracting the economic value by integrated utilization of space in old communities is crucial for encouraging independent participation from enterprises and residents, reducing reliance on government leadership and fiscal investment. This study starts from the active perspective of spatial assets, constructs a value activation framework for old community spatial assets by balancing "endogenous demand" and "exogenous opportunities." By enhancing "economic value" through "use value," five methods for value extraction and overall project utilization paths are proposed, guided by a dynamic "cost-revenue" balance. Using multi-source data, we identify the spatial assets of 1,096 old communities in central Guangzhou and apply a market comparison method for economic value assessment. Additionally, the study offers recommendations on timing and project portfolios for regeneration efforts, along with strategies for establishing a coordinating implementation entity and fund account. This research provides strategic insights for advancing the regeneration of old communities by tapping into their macro-level economic potential.

Lake sediment records are of great importance for understanding the evolution of watershed environments. Various studies have been carried out to constrain the depositional ages of lake sediments and examine their physical, chemical, and biological characteristics, aiming to construct historical vegetation, environment and climate patterns in Chinese lake watersheds. In this study, we obtained relevant literature on lake sediment records by searching the key word 'age-depth' from the databases – Web of Science and China National Knowledge Infrastructure (CNKI, the largest Chinese academic database). We analyzed the literature based on its type (published in a Chinese/English journal or as a Master’s/PhD thesis), period of publication, journal (if published in a journal), key authors, study area, dating scale, and main aims. The results suggest that the lakes in the plateau regions are the most popular research topic typically covering 100–200 years (short-term) and 500–30,000 years (long-term). The literature focuses on a wide range of topics, from past environmental evolution in the watershed to lake ecology, and provides a solid foundation for better understanding regional climate change and the preservation of lake environments and ecosystems. In the future, resulting data from environmental reconstruction with lake sediments will be needed to integrate with emerging information processing technologies (e.g., artificial intelligence and meta-analysis), to disentangle the complex interplay between Earth surface processes and global climate change; furthermore, strengthening interdisciplinary collaboration will deepen our comprehension of man-land relationship and promote the sustainable management of lake ecosystems in the context of global climate change.

In order to quickly develop a multi ship collaborative collision avoidance plan in multi ship encounter scenarios, a multi ship collision avoidance decision model is proposed in accordance with the requirements of the International Maritime Collision Avoidance Regulations, taking into account the collision avoidance operations in multi ship encounter scenarios. Firstly, the collision risk between ships is determined by the closest encounter distance (DCPA) and closest encounter time (TCPA). Secondly, a decision objective function is established based on rules, degree of ship deviation, and ship risk. Finally, the prediction mechanism is used to calculate the minimum value of the objective function and complete the collision avoidance decision. The simulation results show that in the scenario of multiple ship encounters, the collision avoidance model can achieve safe collision avoidance with a smaller steering frequency and a shorter col-lision avoidance time. The proposed multi ship collision avoidance model can provide reference for collision avoidance decision-making in multi ship encounter scenarios, which helps to im-prove the collision avoidance efficiency in multi ship collision avoidance

Respiratory Syncytial Virus (RSV) continues to pose a significant challenge, contributing to elevated hospitalization rates among children up to 5 years old, with a disproportionate burden on newborn and infants under 6 months old. The unique characteristics of the young immune system make it prone to altered responses to infections and vaccinations, requiring a tailored approach to disease prevention. The recent approval of the maternal RSV vaccine, (brand name ABRYSVO), represents a pivotal advancement in preventive strategies among newborns and infants, marking a milestone in RSV research as the first market-approved maternal vaccine. The present review examines clinical trial data on both recent and previous vaccine candidates, as well as the licensed vaccine, focusing on the prevention of RSV disease in newborns and young infants through the passive acquisition of antibodies following maternal immunization. Additionally, it evaluates the safety profile of these vaccines.

Understanding HCPs COVID-19 vaccine concerns can provide critical insights to optimize success of the vaccine rollout program as they are a trusted source of health information to patients and the general population. We sought to understand reasons for health care providers’ COVID-19 vaccine hesitancy in Kenyatta National teaching and referral Hospital. From April to July 2021, we interviewed 60 HCPs purposively sampled from the Infectious Disease Unit (IDU) (n=20) and other departments (n=40). We analyzed data using inductive and deductive approaches to understand reasons for COVID-19 vaccine hesitancy. The HCPs had a median age of 37 years, (Interquartile range: [IQR 20.0-58.0]), 57% were female, 30% nurses among other cadres. Most HCPs cited low confidence in the vaccine such as mistrust in healthcare system and government, vaccine safety and efficacy concerns. Constraints such as uncertainty about the second vaccine dose availability, and misinformation caused hesitancy. Further, few were reluctant receiving the vaccine because of perceived herd immunity from a recent COVID-19 infection, and the need for more information before deciding. The study highlights the need to address any misinformation about vaccines safety and efficacy, and ensure accurate information is easily accessible to HCPs which can translate to higher vaccine uptake.

Background/Objectives: Asthma is a chronic inflammatory disorder of the airways affecting over 10% of the global population. It is characterized by airway inflammation, mucus hypersecretion, and bronchial hyperresponsiveness, driven predominantly by type 2 helper T cells (Th2) and type 2 innate lymphoid cells (ILC2s) in a subset of patients. However, a significant portion of asthmatic individuals present with "type 2-low" asthma, often refractory to standard inhaled corticosteroid (ICS) therapy. Therefore, developing innovative therapeutic strategies has become essential. Recent studies have highlighted cannabidiol (CBD) as a promising anti-inflammatory agent capable of modulating immune responses. This study investigates the therapeutic potential of a high-CBD extract (CBD-X) in asthma; Methods: We evaluated the effects of CBD-X on cells involved in asthma pathogenesis using primary human Th2 cells, neutrophils and asthma mouse model; Results: Our findings indicate that CBD-X extract inhibits Th2 differentiation and reduces the secretion of IL-5 and IL-13, which are crucial cytokines in asthma. Additionally, CBD-X significantly reduces pro-inflammatory cytokines IL-8 and IL-6 in neutrophils and impairs their migration, a critical step in airway inflammation. In a murine asthma model, CBD-X administration led to marked downregulation of IgE and pro-asthmatic cytokines, along with reduced leukocyte, eosinophil, and neutrophil infiltration in lung tissues; Conclusions: These results suggest that CBD-X extract could offer a novel, complementary approach to managing both type 2-high and type 2-low asthma by targeting key inflammatory pathways and modulating immune cell behavior.

Despite various interventions in road safety work, fatal and severe road traffic accidents (RTAs) remain a significant challenge leading to human suffering and economic costs. Understanding the multicausal nature of RTAs, where multiple conditions and factors interact, is crucial for developing effective prevention measures in road safety work. This study investigates the multivariate statistical analysis of co-occurring conditions in RTAs, focusing on single-vehicle accidents with single occupancy and personal injury on Austrian roads outside built-up areas from 2012 to 2019. The aim is to detect recurring combinations of accident-related variables, referred to as blackpatterns (BPs), using the Austrian RTA database. The study proposes Fisher’s exact test to estimate the relationship between an accident-related variable and fatal and severe RTAs (severe casualties). In terms of pattern recognition, the study develops the maximum combination value (MCV) of accident-related variables, a procedure to search through all possible combinations of variables to find the one that has the highest frequency. The accident investigation proceeds with the application of pattern recognition methods, including binomial logistic regression and a newly developed method, the PATTERMAX-method, created to accurately detect and analyse variable-specific BPs in RTA data. Findings indicate significant BPs contributing to severe accidents. The combination of binomial logistic regression and the PATTERMAX-method appears to be a promising approach to investigate severe accidents, providing both insights into detailed variable combinations and their impact on accident severity.

Synergistic control of emissions of air pollutants and CO2 is critical to the dual challenges of air quality improvement and climate change in China. Based on the emission inventories of thermal power units in Beijing, Tianjin, and Hebei, this study analyzes the CO2 and NOX emission characteristics of these units, identifies and quantifies the synergistic drivers affecting these emission trends. Inventory data show that between 2010 and 2020, NOX emissions were reduced by 86.1%, while CO2 emissions were reduced by only 29.8%. Although significant progress has been made in reducing NOX emissions through measures such as end-of-pipe treatment, controlling CO2 emissions remains a difficult task. The index decomposition analysis reveals that economic growth is the main driver of CO2 and NOx emission growth, energy intensity reduction is the main driver of CO2 emission reduction, and end-of-pipe treatment is the main driver of NOX emission reduction. Currently, coal occupies about 87% of the energy consumption of thermal power units in the Beijing-Tianjin-Hebei, and remains the main type of energy for synergistic emissions, and the potential for emission reduction in the energy structure remains huge. For NOX emissions, it is expected that 90% of the reduction potential can be achieved through energy restructuring and end-of-pipe treatment. In conclusion, the high-precision unit-by-unit emission study confirms the effectiveness of the control policy for thermal power units in the region and provides some scientific reference for future policy formulation.

Pregnancy planning and genetic testing (PPGT) has emerged as a tool in reproductive healthcare, offering parents-to-be insight in their risks of having a child with a genetic disorder. This paper reviews the advantages, drawbacks and challenges associated with PPGT, providing some practical guidance for health care professionals. Advantages include identification of genetic risks, a possibility to informed reproductive decision-making, and the potential to reduce the parents-to-be risk for an affected child. Challenges and drawbacks include provision of service, ethical considerations, genetic counselling complexities, and the need to increase public and professional awareness by comprehensive education and accessibility. Practical guidance involves considerations for selecting appropriate candidates, counselling strategies, and how to integrate PPGT into existing healthcare frameworks. By addressing these factors, PPGT can offer an increased reproductive informed choice for the individual and the couple reducing the burden of disease in the family.

Adhesive-invasive E. coli have been suggested to be associated with the development of Crohn's disease (CD). It is assumed that they can provoke the onset of the inflammatory process as a result of the invasion of intestinal epithelial cells, and then, due to survival inside macrophages, stimulate chronic inflammation and the development of granuloma. In previous reports, we have shown that passage of the СD isolate ZvL2 on minimal medium M9 supplemented with sodium propionate (PA) as a carbon source stimulates, and with glucose - inhibits the adherent-invasive properties and the ability to survive in macrophages. This effect was reversible and not observed for the laboratory strain K12 MG1655. We were able to compare the isogenic strain AIEС in two phenotypes - virulent (ZvL2-PA) and non-virulent (ZvL2-GLU). We showed that, unlike ZvL2-GLU, the ZvL2-PA activates the production of ROS and cytokines when interacting with neutrophils. The laboratory strain does not cause a similar effect. Differences in neutrophil NADH-oxidase activation and ζ potential for ZvL2-GLU and ZvL2-PA are associated with changes in the abundance of membrane proteins. Using differential 2D electrophoresis and LC-MS, we identified membrane proteins that may be associated with the activation of the virulence properties of the СD isolate ZvL2.

This study proposes an innovative pharmacovigilance approach, VIGI-4, leveraging ChatGPT Teams Pro version. Our method involves aggregating data from all phase 4 studies published in February 2024 to identify adverse reactions. These results are categorized by disease state alphabetically, demonstrating the method's capacity to generate structured and easily navigable outputs. The results section is tailored to exemplify the valuable, actionable insights attainable through our workflow. This research emphasizes the game-changing potential of integrating advanced technologies such as ChatGPT into pharmacovigilance, signaling a new era in safeguarding drug safety.

This study aims to spatially analyze the distribution characteristics of vacant homes in Asan-si, Chungcheongnam-do, and understand the differences in factors causing vacant homes by type. We use a variety of statistical methods to examine these factors and identify key influencing factors such as the number of vacant stores, changes in overall population, land use complexity, and physical characteristics of land and buildings. The findings reveal that the factors contributing to the occurrence of vacant homes vary significantly by region and property type, highlighting the need for region-specific policies. For instance, in old town areas, small lot ratios and land use complexity are significant, while in rural village, the average number of floors and land use complexity play a major role. This study underscores the diversity of factors influencing vacant homes, suggesting that policies should be tailored to the unique characteristics of different regions to effectively address this issue.

The paper focuses on the application of a multilevel, integrative and territorial approach to the protection of cultural heritage through planning instruments in Serbia. It points out the problems of the sectoral approach and discusses international recommendations that can be integrated into the planning methodology. The case study is the area of Djerdap National Park, which has an already established international and national importance. The research suggests that the cultural heritage in the area, with the exception of the Roman limes, is still recognized at the level of individual localities. The study emphasizes the importance of aligning all levels of governance to safeguard the whole spatial entity rather than focusing solely on its particular areas. The interna-tional and national importance of the planning area contributes to the strengthening of awareness of heritage and its institutional protection. However, the vitality of the area, which is key to its sustainable development, comes from the local level. Planning documents contribute to the inte-gration of local values and local communities into development programs and projects.

The Upper Hunter Valley is a major coal mining area containing approximately 40% of the currently identified total coal reserves in New South Wales (NSW), Australia. Due to the ongoing increase of mining activities, PM10 (air-borne particle with an aerodynamic diameter less than 10 micrometres) pollution has become a major air quality concern in local communities. This paper summarises the spatial and temporal variability modes of PM10 pollution in the region, based on long-term multi-site monitoring data and the application of the rotated principal component analysis (RPCA) and wavelet analysis techniques. RPCA identified two distinct air quality clusters/subregions in the valley, one in the west/northwest, the other in the southeast. Wavelet analysis revealed the annual cycle to be most persistent temporal mode of PM10 variability in both subregions, with intermittent signals observed at time scales of around 120, 30~90 and under 30 days. How these variation modes are related to the effects of local PM10 emissions and the influence of meteorology at different time scales deserves further attention in future work. The findings will be used in air quality reporting and forecasting in NSW. The methodology and results can also be useful for air quality research in similar regions elsewhere.

How hematopoietic stem and progenitor cell (HSPC) fate decisions are affected by genetic alterations acquired during AML leukemogenesis is poorly understood and mainly explored in animal models. Here, we studied isocitrate dehydrogenases (IDH) genes mutations in the human model of HSPC and provide a review of the literature on this topic. IDH1/2 mutations occur in ~20% of AML, are recognized among the mutations earliest acquired during leukemogenesis, and are target of specific inhibitors (ivosidenib and enasidenib, respectively). In order to investigate the direct effects of these mutations on the HSPC we expressed by lentiviral transduction either IDH1-R132H or IDH2-R140Q mutants into human CD34+ healthy donor cells and analyzed the colony-forming unit (CFU) ability. CFU ability was dramatically compromised with a complete trilineage block of differentiation. Strikingly, the block was reversed by the specific inhibitors, confirming it was a specific effect induced by the mutants. In line with this observation, the CD34+ leukemic precursors isolated from a patient with IDH2-mutated AML at baseline and during enasidenib treatment showed over time a progressive and marked improvement of their fitness in terms of CFU ability and propensity to differentiate, attaining clonal trilinear reconstitution of hematopoiesis and complete hematological remission.

Questions：SAP in mountainous cities of China serve as crucial carriers for species and wild food, constituting potential green infrastructure. These patches should be recognized as locally specific resources. This study investigates the transformation characteristics of the landscape patterns of SAP, along with their elements, across urban-rural gradients, providing foundational support for the planning of conservation and utilization strategies. Location: Yongchuan area of Chongqing in southwest China. Methods: The study investigated urban-rural gradient-based transformation of SAP. A four-direction transect space was selected and divided into uniform sample squares. Fragstats 4.3 calculated the landscape index of SAP, and Spearman correlation coefficients in SPSS were used to evaluate the influence of landform and artificial factors on agroforestry patch transformation. Results: 1) Patch area (PA), Plaque density (PD), and CLUMPY of SAP systematically transform, showing increased SAP areas and higher connectivity with greater distance from the city, resulting in reduced patch fragmentation. However, Edge density (ED) and Largest plaque index (LPI) exhibit irregular transformation patterns. 2) With increased distance from the city, woodland patch area and connectivity increase, leading to decreased fragmentation, dispersal, and lower fractal dimensions. Conversely, Cultivated land follows the opposite trend. garden land patch area, fractal dimension, fragmentation, and dispersal all increase, while connectivity decreases. 3) Landscape pattern transformations of SPA are significantly influenced by artificial factors. Woodland patches are influenced similarly by landform and artificial factors. In contrast, cultivated land and garden land patches are more significantly impacted by artificial factors. Conclusions: SAP exhibit differentiated conservation and utilization measures across urban-rural gradients. Small patches located far from urban centers may benefit from systematic conservation measures to prevent further fragmentation and erosion in peri-urban areas.

Present study on land use land cover analysis and taluka wise combination of cropped area, carried out in Beed district of Maharashtra state in India and studied 11 talukas of the district. Secondary data on land use land cover and area in various crops has been collected, compiled and analyzed from various secondary sources. Simple descriptive statistics used to examine the agricultural land use land cover and J.C. Weaver’s crop combination technique was used for taluka wise analysis of crop combinations and on the basis of highest to smallest area engaged in particular crop, crops have been ranked. The study showed that, in the district as a whole, percentage of uncultivated land other than fallow was about 46 percent as compare to net sown area is only 35 percent in total geographical area (1063855ha) of Beed district. The study further revealed that about 42 percent area engaged in food crops and about 58 percent area occupied by nonfood crops, which includes cereals (25%), cotton (19%), pulses (13%), oilseed (12%), sugarcane (5%) and fruits and vegetables (3%). Results of Weaver’s crop combination technique showed that the Wadwani taluka demarcated as most diversified taluka by means of maximum number (sixteen) of crops combinations with the lowest variance value (14) found in the present investigation. Further, the study revealed that the high crop diversity found in Dharur taluka with eighteen crop combinations and the taluka has given first rank amongst others. To derive the crop diversity ranking, taluka wise maximum to minimum number of crop combinations derived in different talukas and given ranks accordingly. The study concluded that, agricultural land use analysis is essential for solving and optimizing the land use problem, maintaining socio-ecological balance, best utilization of scarce resources. The authors enlightened that the rational use of agricultural land has important for food security and biodiversity which increase the productivity and profitability of the agriculture sector and it indicates the decision making ability of farmers in study area.

This paper is focused on typical rural settlements in the Stara Planina Mountain area in Serbia. They are distinguished by their authenticity, identity and character, and they have still not been destroyed by inappropriate development as is the case in some other mountain areas in Serbia, where the effects of urbanization, globalization and homogenization are obvious. Consequently, there is a need to prevent these effects in mountain areas where there is a threat of disbalance between development and the inherited natural and cultural values. The paper starts from several important concepts that relate contemporary approaches to cultural heritage preservation, place morphology and planning future development. The concept definitions from recent documents from related fields are used. These concepts are then applied to the area of Stara Planina Mountain and its rural settlements. The necessity for an integrative approach to planning this area with significant natural and anthropogenic potential is pointed out, including its integration into international programs of sustainable development.

This research investigates the lane width standards and guidelines implemented by various State Departments of Transportation (DOTs) to reduce vehicle speeds and enhance road safety. Lane width reduction is often perceived as a strategy to mitigate speed and improve safety. Still, its effectiveness and implications vary across different contexts, including regions, urban/rural settings, or other geometric design features. Drawing from interviews with five State DOTs and a review of their road design manuals, this study aims to identify suggested lane widths depending on the contexts, design exception process when narrowing or widening lane widths, and introduce representative before/after studies. The findings indicate that State DOTs tend to have lower recommended lane widths in urban areas than in rural areas. Moreover, lane width standards among these states vary due to several factors, including the geographical location of roadways (urban or rural areas), design or posted speeds, traffic volume, road classification, and geometric road design features. Design exceptions are required if the existing or proposed design element is incompatible with both AASHTO and department governing criteria. In conclusion, the findings will provide valuable insights and recommendations for policymakers, transportation planners, and road engineers to inform optimal lane width and decision-making processes.

Bosentan, an endothelin-receptor antagonist (ERA), has potential anti-atherosclerotic properties. We investigated the complementary effects of bosentan and atorvastatin on the progression and composition of the atherosclerotic lesions in diabetic mice. Forty-eight male apoE-/- mice were fed high-fat diet (HFD) for 14 weeks. At week 8, diabetes was induced with streptozotocin and mice were randomized into 4 groups: 1) Control/COG: no intervention. 2) ΒΟG: bosentan 100 mg/kg/day per os. 3) ATG: atorvastatin 20mg/kg/day per os). 4) BO+ATG: Combined administration of bosentan and atorvastatin. The intra-plaque contents of collagen, elastin, monocyte chemoattractant protein-1 (MCP-1), tumor necrosis factor-a (TNF-a), matrix-metalloproteinases (MMP-2,-3,-9), and TIMP-1 concentrations were determined. The percentage of lumen stenosis significantly decreased across all treated groups: BOG: 19.5±2.2%, ATG: 12.8±4.8%, BO+ATG: 9.1±2.7% compared to controls (24.6±4.8%, p<0.001). Both atorvastatin and bosentan significantly increased collagen content and fibrous cap thickness versus COG (p<0.01). All intervention groups reduced the relative intra-plaque concentrations of MCP-1, MMP-3,-9, and increased TIMP-1 compared to COG (p<0.001). Importantly, bosentan showed modest but additive to atorvastatin effects on the latter parameters compared COG (p<0.05). Bosentan treatment in diabetic, atherosclerotic apoE-/- mice delayed the atherosclerosis progression and enhanced plaques’ stability, showing modest but complementary effects with atorvastatin, which are promising in atherosclerotic cardiovascular diseases.

Background: Lutein and zeaxanthin are fat-soluble antioxidant nutrients that have evidence of beneficial effects on vision and eye health. The purpose of this study was to examine the effects of supplementation with lutein and zeaxanthin isomers (Lute-gen®) on eye health, eye strain, sleep quality, and attention in high electronic users. Study design: Two-arm, 6-month, parallel-group, randomized, double-blind, placebo-controlled trial. Methods: Seventy volunteers aged 18 to 65 who used electronic screens for more than 6 hours daily were supplemented with 10 mg of lutein and 2mg of zeaxanthin-isomers or a placebo. Outcome measures included several ophthalmic examinations comprising the Schirmer tear test, photo-stress recovery time, contrast sensitivity, tear film break-up time, and self-report measures of visual fatigue, computer vision, sleep quality and attention. Results: Compared to the placebo, lutein and zeaxanthin supplementation was associated with greater improvements in the Schirmer tear test, photo-stress recovery time, and tear film break-up time. However, there were no group differences in the change in self-report measures or contrast sensitivity. Lutein and zeaxanthin supplementation was well-tolerated, with no reports of serious adverse reactions or clinically significant changes in safety blood measures, including liver function, renal function, blood lipids, and full blood examination. Conclusions: The results from this study provide support for the beneficial effects of 6 months of lutein and zeaxanthin supplementation on visual health and dry eyes in regular users of electronic screens. However, these findings were not corroborated by group differences in the administered self-report questionnaires.

The aim of this study was to investigate the relationship between postprandial glycemic levels based on flash-monitoring and the production of intestinal hydrogen (H2) and methane (CH4) gases based on measurement of the amount of these gases in exhaled air. We studied 14 subjects with type 2 diabetes mellitus (T2DM) and 10 individuals without diabetes (control) with 3 food-load tests with simultaneous determination of gases in exhaled air and assessment of glucose levels. In 15.4% of patients with T2DM, there was a non-significant increase in exhaled H2. How-ever, all subjects in the control group had significant increase in exhaled H2. Moreover, the level of H2 in exhaled breathafter food load in patients with T2DM was lower than in normoglycemic subjects. Also, in normoglycemic subjects there was an inverse correlation between maximum glucose rise and maximum H2 in exhaled air after food load. At the same time in patients with T2DM the level of CH4 in exhaled air directly correlated with the parameters of postprandial glycemia in the test with lactulose. Confirmation of a causal relationship between decreased H2 production, increased intestinal CH4 production, and more severe postprandial glycemia may identify new therapeutic targets in the correction of postprandial glycemia in patients with T2DM.

On February 28th, 2023, Spanish Royal Decree 150/2023 as published, approving the plans for the management of the maritime space of the five Spanish marine demarcations. This Royal Decree Law inaugurates the Planning of the Maritime Space in Spain. Terrestrial Space Planning is very advanced, both in the legislation and in the instruments that are enabled to organize this space, from the national scale to the municipal scale, passing through the regional, provincial, and supra-municipal scales. Naturally, both Planning must converge and thus speak of an Integrated Space Planning. In some of the countries that we can take as global references, this convergence in the form of integration is taking place. On the other hand, and within the context of climate change, coastal cities will be the most affected, both by the potential rise in sea level and by the increasingly continuous and greater extreme events. Integrated Space Planning is postulated as the most effective tool to carry out adequate territorial and urban planning of our coastal cities, as well as to analyse the influence and possible corrective measures to apply against the effects produced by climate change.

Historically, urban development has always been centered on coastal areas – with access to waterbodies – seas, rivers and canals being a significant advantage for movement and trade. With most of the world’s megapolises located on coasts, land reclamation offers a solution for the expansion of city centers which are otherwise restricted by the coastline. The current understanding of urban regeneration and development on reclaimed lands is defined in this study, answering the basic questions of what, why and how. This study aims to assess the urban regeneration on reclaimed coastal land based on the principles of sustainable development defined by existing studies. The literature review establishes a theoretical framework and defines performance-based benchmarks identifying the spatial indicators of urban development. Composite indicators namely open space coverage, land use mix, percentage of coast for people, accessibility to public transportation and amenities, availability of pedestrian paths and cycling tracks and adequate road networks are considered for this framework. The conclusions are drawn based on the results of the analysis of spatial layout using GIS as a tool to map and empirically measure each indicator. The framework is validated using a major land reclamation project, West Bay, in the coastal urban area of ​​the city of Doha. The results determine that West Bay has achieved a good level of sustainability, although there are areas that could be enhanced to further improve the overall sustainability of urban development. These findings can serve as a guide for policymakers and various stakeholders for sustainable urban planning on reclaimed coastal lands.

In the last decades, the impacts of urbanization on the hydrological cycle have led to an increase in the frequency and magnitude of urban flooding events, also amplified by the effects of climate change. Sustainable Drainage Systems (SuDS) provide a revolutionary change in this field, improving the sustainability and resilience of cities. This research explores the integration of different SuDS with the aim of significantly reducing both flow volume and celerity of floods in a residual urban catchment area of metropolitan city of Querétaro (Mèxico), where extreme rainfall frequently occurs. This catchment is a representative suburb of urban pressure and environmental degradation problems. Currently, managing storm water under climate uncertainty through a multi-disciplinary approach is a major concern in this urban area. A 1D-2D coupling model of shallow water equations, finite volume method, unstructured meshing method, and hybrid parallel computing application defined the optimal configuration of SuDS at catchment scale to reduce the flood vulnerability in Querétaro. Specifically, in this paper we explore the management issues of the proposed SuDS configuration that acts as a water resource system with multiple purposes. A generic simulation model called MODSIM was applied to simulate the designed urban drainage system under a balanced IPCC future climate scenario in terms of reliability, resilience and vulnerability against water scarcity.

The observation that certain therapeutic strategies for targeting inflammation benefit patients with distinct immune-mediated inflammatory diseases (IMIDs) is exemplified by the success of TNF blockade in conditions including rheumatoid arthritis, ulcerative colitis and skin psoriasis, albeit only for subsets of individuals with each condition. This suggests intersecting "nodes" in inflammatory networks at a molecular and cellular level may drive and/or maintain IMIDs, being “shared” between traditionally distinct diagnoses without mapping neatly to a single clinical phenotype. In line with this proposition, integrative tumour tissue analyses in oncology have highlighted novel cell states acting across diverse cancers, with important implications for precision medicine. Drawing upon advances in the oncology field, this narrative review will first summarise learnings from the Human Cell Atlas in health as a platform for interrogating IMID tissues. It will then review cross-disease studies to date that inform this endeavour, before considering future directions in the field.

Some preterm and sick neonates have altered biochemical profiles and follow-up newborn screening (NBS) collections are recommended. The Victorian NBS program historically recommended recollections for babies with birth weight <1500g (managed by the maternity service provider) and 3 weeks post-transfusion (managed by the laboratory). We aimed to determine adherence to current guidelines and review the guidelines to improve NBS performance. To do this we audited data from 348,584 babies between January 2018 and June 2022. Babies with a recorded birth weight of <1500g were filtered for inclusion. For the overall review and visualization of the protocol, we sourced information from the literature, our professional society and tertiary hospital services. A total of 2647 babies had a birth weight recorded between 200 and 1499g. Of these 2036 (77%) had a second sample collected, indicating that >1 in 5 babies were not receiving a follow-up collection. Our timing of recollections for transfused babies, requiring a 3-week follow-up collection, was longer than in other Australasian jurisdictions. A new combined “sick-prem-protocol” was launched to support recollections and after a one-year review achieve 95% compliance. We recommend NBS laboratories audit preterm and sick neonate recollections to ensure appropriate follow-up. This should be supported with a visual process map to aid education and compliance.

Mobile inspections conducted by intelligent tunnel robots are instrumental in broadening the inspection reach, economizing on inspection expenditures, and augmenting the operational efficiency of inspections. Despite differences from fixed surveillance, mobile-captured traffic videos have complex backgrounds and device conditions that interfere with accurate traffic event identification, warranting more research. This paper proposes an improved algorithm based on YOLOv9 and DeepSORT for intelligent event detection in edge computing mobile device using the intelligent tunnel robot. The enhancements comprise the integration of the Temporal Shift Module to boost temporal feature recognition and the establishment of logical rules for identifying diverse traffic incidents in mobile video imagery. Experimental results show that our fused algorithm achieves a 93.25% accuracy rate, an inprovement of 1.75% over the baseline. The algorithm is also applicable to inspection vehicles, drones, and autonomous vehicles, effectively enhancing the detection of traffic events and improving traffic safety.

Background: Two explored EDA1 variants regulate the biological behaviors of human dental pulp stem cells (hDPSCs), such as proliferation and migration, as well as their effects on odontogenic differentiation, providing a theoretical basis for further exploration of the mechanisms underlying EDA1-induced tooth development. Methods: The experimental groups included a wild-type EDA1 group (Wt), non-syndromic tooth agenesis variants EDA1 group (NSTA-A259E, NSTA-S374R), syndrome type variant EDA1 group (STA-H252L), and an empty vector control group (PCR3/NC). CCK-8 method was used to investigate the proliferative activity of hDPSCs. The cell cycle distribution of hDPSCs was detected by flow cytometry; The cell migration ability was assessed using the cell scratch and Transwell tests; Odontogenic differentiation medium was used to induce mineralization of hDPSCs, followed by statistical analysis. RNA-Seq revealed that FOS, JUN and other genes were found to be enriched in MAPK signaling pathway and osteoclast differentiation pathway. qPCR was used to detect mRNA expression of hub genes (FOS and JUN). Results: Compared with the NSTA-EDA1 and STA-EDA1, Wt-EDA1 promotes the proliferation and transformation of hDPSCs from the G0/G1 phase to S phase (p<0.01), with no significant difference between NSTA-EDA1 and STA-EDA1 (p>0.05). Wt-EDA1 also upregulated hDPSCs cell migration compared to NSTA-EDA1 and STA-EDA variants, as demonstrated by migration assays (p<0.01). NSTA-EDA1 and STA-EDA1 variants inhibited the odontogenic differentiation of hDPSCs compared to the Wt group, as shown by Alizarin red staining and ALP staining (p<0.01). RNA sequencing revealed that the differentially expressed genes FOS and JUN were enriched in the MAPK signaling pathway and osteoclast differentiation. Compared with Wt-EDA1, EDA1 variants lost the ability to promote c-FOS mRNA expression, as confirmed by qPCR. Conclusions: EDA1 variants fail to the promote c-FOS mRNA expression in hDPSCs, thereby inhibiting odontogenic differentiation and losing the ability to enhance the proliferation of hDPSCs.

In a trip planning service, travelers first set a starting point, a destination, and a sequential list of specific points of interest types (e.g., museums, restaurants, and parks). Based on this information, the service searches the spatial database to customize the best travel itinerary for the tourist. However, in previous studies, planners only considered the time factor when designing the optimal route, and failed to fully consider the quality of each point of interest. In this study, we specifically leveraged the capabilities of large language model to parse and respond to complex travel-related user queries. To apply large language model to route planning, we fine-tuned the model to understand geotagging and user travel preferences. We have introduced a novel graph search algorithm combined with large language model output, which optimizes the route search process to provide optimal travel recommendations by taking into account various factors such as distance length, budget constraints, and popularity of tourist attractions. In addition, we have integrated real-time traffic data and historical travel data to further improve the prediction accuracy and application usefulness of the model. In the experimental validation phase, we designed a series of benchmarks to compare the performance of the system with traditional algorithms and other machine learning-based route planning methods. Experimental results show that our model has a significant improvement compared with traditional methods in improving the speed and accuracy of path selection.

The ongoing SARS-CoV-2 pandemic has raised concerns surrounding immunological protection against the virus, particularly for people with inborn errors of immunity (IEI). While COVID-19 vaccination induces robust antibody, memory B-cell, and T-cell responses in healthy individuals, how well vaccination protects people with IEI against infection and severe disease remains unclear – especially in the context of new viral variants and vaccine formulations – leading to anxiety, ongoing self-isolation, and repeated vaccination with limited evidence of increased efficacy. Whilst most people with IEI generate some level of cellular and/or humoral immunity to COVID-19 vaccination, the level of protection and durability of the response are unclear. Alongside vaccination, antibody-based therapeutics are aimed at limiting infection and severe disease in this cohort. Immunoglobulin replacement therapy (IgRT) provides passive immunity in antibody-deficient individuals. However, to successfully prevent SARS-CoV-2 infection, a sufficient number of neutralizing antibodies must be present in product. While antibodies against circulating variants are eventually present in IgRT products (both from natural infection and vaccination of the donors), evidence of their capacity to recognize new variants is limited. Furthermore, while antibody-based pre- and post-exposure prophylaxis can be effective, they are susceptible to decreased efficacy in the context of variant evolution. This review provides an in-depth overview of current knowledge about COVID-19 vaccine efficacy in IEIs, the efficacy of SARS-CoV-2-specific antibody products, and knowledge and technological advances required for continued protection of people with IEI.

PCSK9 is implicated in familial hypercholesterolemia via targeting the cell surface PCSK9-LDLR complex toward lysosomal degradation. The M2 repeat in the PCSK9's C-terminal domain is essential for its extracellular function, potentially through its interaction with an unidentified “protein X”. The M2 repeat was recently shown to bind an R-x-E motif in MHC-class-I proteins (implicated in the immune system), like HLA-C, and causing their lysosomal degradation. These findings suggested a new role of PCSK9 in the immune system and that HLA-like proteins could be “protein X” candidates. However, the participation of each member of the MHC-I protein family in this process and their regulation of PCSK9's function have yet to be determined. Herein, we compared the implication of MHC-I-like proteins such as HFE (involved in iron homeostasis) and HLA-C on the extracellular function of PCSK9. Our data revealed that the M2 domain regulates the intracellular sorting of the PCSK9-LDLR complex to lysosomes, and that HFE is a new target of PCSK9 that inhibits its activity on the LDLR, whereas HLA-C enhances its function. This work suggests the potential modulation of the PCSK9 functions through interactions of HFE and HLA-C.

Mental disorders impact a significant portion of the global population, presenting substantial challenges to healthcare systems due to high hospitalization costs and resource demands. This narrative review explores the economic implications of mental health disorders, focusing on hospitalization costs, the effectiveness of interventions, and the outcomes of recent research. Materials and Methods: A narrative review was conducted, sourcing articles from PubMed and Google Scholar published between 2014 and 2024. The search terms included combinations related to mental illness, costs, hospital care, and mental healthcare interventions. A total of 1,110 articles were initially identified, with 37 studies meeting the inclusion criteria after rigorous screening by two independent researchers. These studies included quantitative and qualitative data covering a range of outcomes such as hospital admission rates, consumer satisfaction, and quality of life. The findings of the present review reveal that mental disorders significantly increase hospitalization costs due to frequent admissions, extended stays, and the need for specialized treatments. Additionally, physical comorbidities in individuals with mental disorders lead to higher healthcare costs and resource use. Integrated care models, early intervention, and preventive strategies show promise in reducing these costs and improving patient outcomes. Conclusions: Our review emphasizes the critical need for integrated healthcare strategies that address both mental and physical health to reduce hospitalization costs and improve outcomes. Effective management of mental health disorders requires comprehensive approaches, including complex outpatient services and preventive care. Future research should focus on standardizing methodologies to provide clearer insights into the economic impact of mental health conditions and guide effective healthcare strategies.

The morphological aspects of urban growth on wetlands in Africa are under-researched. Using the Densu Delta Ramsar site in Accra, Ghana, as a case study, this paper analyses the morphological patterns and drivers of urban growth and its impact on wetlands. Data were obtained through remote-sensing, ground truthing and limited key informant interviews. The analysis combined land use/land cover, building coverage and multiple regression techniques, with the aid of GIS and STATA software. The findings reveal that urban growth at the Ramsar site follows discernible spatial patterns consistent with the spreading pancake, village magnet and ribbon development models. However, the primary force behind these patterns is growing demand for land to meet housing needs, aided by the failure of state institutions to perform their land use control and wetland protection functions. To achieve sustainable urban development, there is an urgent need to ensure effective wetland management by enforcing existing land use, development control and wetland protection measures. This calls for the strengthening, resourcing and closer collaboration between the various state agencies responsible for urban planning and wetland management. There is also the need to engage and sensitise political leaders to increase their commitment to implementing wetland protection and pro-environmental policies.

Confronting the dual challenges of rapid urbanization and climate change, although extensive research has investigated the influencing factors and practical strategies of urban carbon emissions and urban vibrancy, respectively, the unclear mutual nexus between them and the development strategy of collaborative optimization requires further in-depth analysis. This study explores the delicate balance between urban vibrancy and low-carbon sustainability within the confines of Beijing’s Fifth Ring Road. By integrating OpenStreetMap, land use, population, and building carbon emission data, we have developed a reproducible method to estimate total carbon emission and emission intensity per capita. Furthermore, we have introduced vibrancy index data to distinguish the vibrancy evaluation of residential and non-residential land and applied cross-combinational classification technology to dissect the spatial correlation between urban carbon emissions and urban vibrancy. The results reveal that the four combination typologies show more significant differences and regularity in residential land. Based on the discovery of spatial correlation, this study puts forward corresponding development strategy suggestions for each typology based on geographical location and the requirements of urban development policies of these four combination typologies. In conclusion, our study highlights the importance of integrating carbon emissions and urban vibrancy comprehensively in sustainable urban planning and proposes that various land use combinations need targeted development strategies to achieve this goal, which need to consider population, energy, service facilities, and other diverse aspects.

Globalization, knowledge economy, information technology advancements, and the rise of learning societies contribute to the concept of a learning city. The study examines the economic indicators of Yazd city, Iran, in the context of learning city development. A descriptive-analytical approach with a survey method and cluster sampling was employed. Data analysis involved Kolmogorov-Smirnov normality test, single-sample T-test, simple linear regression, and Kendall's W test. The normality test confirmed data normality. The T-test indicated that experts perceived the current state of most variables in Yazd as undesirable. Regression analysis revealed a significant positive association between the economic index and independent variables. Kendall's W test prioritized areas based on economic indicators, with the top 7 and bottom 5 areas identified for focused interventions. The study emphasizes the need to prioritize areas within Yazd based on their economic indicators. This prioritization informs strategies for enhancing social and legal aspects of Yazd's transformation into a learning city. Further research should explore effective methods to cultivate a full-fledged learning environment in the city.

Human papillomavirus (HPV) is the most sexually transmitted infection associated with the development of cervical cancer. This study investigated cervical HPV prevalence, characteristics and distribution according to age and human immunodeficiency virus (HIV) among women attending public community health facility in the Eastern Cape Province of South Africa. A total of 325 participants (aged 18 to 60) visiting a community health facility for any reason were recruited. Cervical HPV infection was detected using the Seegene Anyplex™ II HPV28 assay. Overall HPV prevalence was 65.2% (95% CI: 59.9–70.2%), with the highest prevalence of 80.9% (95% CI: 67.2–89.8%) observed in the 18–25 years age group and lowest prevalence of 46.3% (95% CI: 35.8–57.1%) in 46–60 years of age. HR-HPV infection was found to decrease with increasing age among women who were HPV infected by any type (p=0.02), but not when stratified according to HIV status. A proportion of 12.9% (42/325) were infected with one or more HPV types covered by the Cervarix® HPV vaccine (HPV-16 and/or -18), 18.8% (61/325) by those covered by Gardasil®4 (HPV-6, -11, -16 and/or -18) and 42.2% (137/325) by those covered by Gardasil®9 (HPV-6, -11, -16, -18, -31, -33, -45, -52 and/or -58). Alpha-9 HPV species were the most dominant species (40.6%, 132/325), followed by alpha-7 species (29.8%, 97/325). In the overall population, alpha-9 HPV species were always part of the most dominant HPV alpha species co-infection, which were alpha-9 and -7 species (17.5%, 57/325), alpha-9 and -5 species (9.8%, 32/325), and alpha-9 and -6 species (9.5%, 31/325). High overall HPV, HR-HPV, and alpha-9 species prevalence were observed among women attending the public health facility. These findings contribute to the limited HPV distribution data among Eastern Cape women, which could be used to improve HPV-related policy and assess the effectiveness of the HPV vaccination.

Long COVID, a name often given to the persistent symptoms following acute SARS-CoV-2 infection, poses a multifaceted challenge for health. This review explores the intrinsic relationship between comorbidities and autoimmune responses in shaping the trajectory of long COVID. Autoantibodies have emerged as significant players in COVID-19 pathophysiology, with implications for disease severity and progression. Studies show immune dysregulation persisting months after infection, marked by activated innate immune cells and high cytokine levels. The presence of autoantibodies against various autoantigens suggests their potential as comorbid factors in long COVID. Additionally, the formation of immune complexes may lead to severe disease progression, highlighting the urgency for early detection and intervention. Furthermore, long COVID is highly linked to cardiovascular complications and neurological symptoms, posing challenges in diagnosis and management. Multidisciplinary approaches, including vaccination, tailored rehabilitation, and pharmacological interventions, are used for mitigating long COVID's burden. However, numerous challenges persist, from evolving diagnostic criteria to addressing the psychosocial impact and predicting disease outcomes. Leveraging AI-based applications holds promise in enhancing patient management and improving our understanding of long COVID. As research continues to unfold, unravelling the complexities of long COVID remains paramount for effective intervention and patient care.

Circulating tumor cells (CTCs) are cells released from the primary tumor and intravasate into the blood or lymphatic vessels, where they are transported to distant sites and act as seeds that initiate cancer metastases. Recent advances in CTC research have shown their relevance as prognostic markers for early and metastatic disease detection, predictive biomarkers for relapse, and response to medical intervention or therapy. The rapidly evolving landscape of CTC biology has opened new avenues for understanding cancer progression, metastasis, and treatment response. Additionally, translating these findings into clinical applications holds promise for improving cancer diagnostics, prognosis, and personalized therapeutic strategies. This review discusses the significance of CTCs in cancer research and their associated challenges. We explore recent developments in the detection and characterization of CTCs and their implications in cancer research and clinical practice.

This study analyses regional development in one of the poorest provinces in China, Guizhou Province, between 2000 and 2012 using a multiscale and multi-mechanism framework. In general, regional inequality has been declining since 2000. In addition, economic development in Guizhou Province presented spatial agglomeration and club convergence, which shows how the development pattern of one core area, two-wing areas and a contiguous area at the edge of the province have been developed between 2006 and 2012. Multilevel regression analysis revealed that industrialization and investment level were the primary driving forces of regional economic disparity in Guizhou Province. The influences of marketization and decentralization on regional economic disparity were relatively weak. Investment level reinforced regional economic disparity and the development of core-periphery structure in the province. However, investment level actually weakened the regional economic disparity in Guizhou Province when the variable of time was considered. In addition, both the topography and urban–rural differentiation were the two main reasons for forming a core-periphery structure in Guizhou Province.

European strategic policy directions towards a sustainable blue economy have strengthened interest in maritime investments, thus increasing sectoral competition for marine space. Emerging repercussions out of such a rising interest need to be handled by Marine Spatial Planning (MSP) as a means for: properly allocating marine space to diverse uses; managing conflicts and promoting synergies among them; and pursuing a multi-use perspective of this space. A critical stage of each MSP exercise is the exploration of land-based spatial/developmental directions and their current or potential repercussions in the marine environment in order for constraints but also perspectives in policy choices/maritime uses in the MSP context to be featured; and attainment of a successful coherence or coordination between land and marine spatial/developmental policies to be ensured, by analyzing Land-Sea-Interaction (LSI) and embedding it in the MSP. The latter is the focus of this paper aiming to illuminate critical issues emerging from land-based (terrestrial) policy frameworks for feeding MSP endeavors; and is accomplished in the Northern Aegean Sea, Greece. Towards this end, a multilevel approach is adopted, delving into diverse policy contexts at the local, regional and national/European level and aiming to attain more informed MSP decisions in the specific study region.

Curcumin, a hydrophobic polyphenol compound derived from the rhizome of the Curcuma genus, has a wide spectrum of biological and pharmacological applications. Previously, curcumin nanoparticles with different stabilizers had been produced successfully in order to enhance solubility and per oral absorption. In the present study, we tested the anti-inflammatory effect of D-α-Tocopheryl polyethylene glycol 1000 succinate (TPGS)-stabilized curcumin nanoparticles in vivo. Lambda-carrageenan (λ-carrageenan) was used to induce inflammation in rats; it was given by an intraplantar route and intrapelurally through surgery in the pleurisy test. In the λ-carrageenan-induced edema model, TPGS-stabilized curcumin nanoparticles were given orally one hour before induction and at 0.5, 4.5, and 8.5 h after induction with two different doses (1.8 and 0.9 mg/kg body weight (BW)). Sodium diclofenac with a dose of 4.5 mg/kg BW was used as a standard drug. A physical mixture of curcumin-TPGS was also used as a comparison with a higher dose of 60 mg/kg BW. The anti-inflammatory effect was assessed on the edema in the carrageenan-induced paw edema model and by the volume of exudate as well as the number of leukocytes reduced in the pleurisy test. TPGS-stabilized curcumin nanoparticles with lower doses showed better anti-inflammatory effects, indicating the greater absorption capability through the gastrointestinal tract.

SOC stock (SOCS) changes caused by land use changes are still unclear, and understanding this response is essential for many environmental policies and land management practices. In this study, we investigated the temporal-spatial and vertical distribution characteristics of SOCS on the Western Sichuan Plateau (WSP) using the sparrow search algorithm-random forest regression (SSA-RFR) models with excellent model applicability and accuracy. The temporal-spatial varia-tions in the SOCS were modeled using 1080 soil samples and a set of nine environmental covariates. We analyzed the effect of land use changes on the SOCS on the WSP. The total SOCS increased by 18.03 Tg C from 1990 to 2020. The results of this study confirmed that the SOCS in the study area has increased significantly since 2010, with an increase of 27.88 Tg C compared to the total SOCS in 2010. We found that the spatial distribution of the SOCS increased from southeast to northwest, and the vertical distribution of the SOCS in the study area decreased with increasing soil depth. Forest and grassland are the main sources of SOCS, the total SOCS in the forest and grassland accounted for 37.53 and 59.39% of the total SOC pool in 2020, respectively. Expansion of the wetlands, forest, and grassland areas could increase SOCS in the study area.

Esophageal cancer is an extremely deadly tumor that accounts for 5% of all cancer deaths. The two main subtypes of the disease are esophageal squamous cell carcinoma (ESCC) and esophageal adenocarcinoma (EAC). To date, few studies analyse EAC for transcriptional signatures associated with diagnosis and/or prognosis, while most focus on the analysis of transcriptional profiles of ESCC. In this study, we used single-cell RNA sequencing (scRNA-seq) analysis of CD45+ cells enriched from Tumors and matched Non Tumor tissues from therapy naїve patients to identify all types of immune cells present in tumor immune infiltrate and its transcriptional profile. In addi-tion, we analysed the entire transcriptome in a cohort of 23 patients whose tissue biopsies were taken from Tumors and matched with Non Tumor tissue. The transcriptional signatures we obtained were then used to stratify a large cohort of TCGA EAC patients, demonstrating a strong association with their prognosis, as well as the ability to predict a patient's clinical outcome and better define the prognosis of EAC after surgery. In addition, these features may lead patients to effective therapies including immunotherapy approaches.

Although, promotion of urbanization culture in recent decades has made inevitable development of cities in the world, however, the development can be guided in a direction that leave, to the extent possible, minimum socioeconomic and environmental impacts. For this, it is required to first forecast auto-spreading orientation of cities and suburbs in rural areas over time and then avoid shapeless growth of cities. This paper is an attempt to develop a dynamic hybrid model based on logistic regression (LR), Markov chain (MC), and cellular automata (CA) for prediction of future urban sprawl in fast-growing cities. The model was developed using 12 widely-used urban development criteria, whose significant coefficient was determined by logistic regression, and validated by relative operating characteristic (ROC) analysis. The validated model was run in Guilan, a tourist province in northern Iran with a very high rate of urban development. For this, changes in the area of urban land use were detected over the period of 1989 to 2013 and then, future sprawl of the province was forecasted by the years 2025 and 2037. The analysis results revealed that the area of urban land use was increased by more than 1.7 % from 36012.5 ha in 1989 to 59754.8 ha in 2013, and the area of Caspian Hyrcanian forestland was reduced by 31628 ha. The results also predicted an alarming increase in the rate of urban development in the province by the years 2025 and 2037, during which urban land use is predicted to develop 0.9 % and 1.38 %, respectively. The development pattern is expected to be uneven and scattered, without following any particular direction. The development will occur close to the existing or newly-formed urban basements as well as around major roads and commercial areas. This development, if not controlled, will lead to the loss of 13863 ha of Hyrcanian forests and if the trend continues, 21013 ha of Hyrcanian forests and 20208 ha of Barren/open lands are expected to be destroyed by the year 2037. In general, the proposed model is an efficient tool for the support of urban planning decisions and facilitates the process of sustainable development of cities by providing decision-makers with an overview on future development of cities where the growth rate is very fast.

A previous research showed the 1755 tsunami would inundate the Marginal Avenue, the railway and the low ground area of Caxias, Oeiras municipality, Portugal. Thus, in this study several proposals for coastal protection are presented. A new Lidar data of local topography allowed the construction of a more accurate DEM, including the representation of the streets of Caxias downtown, to be used in the tsunami numerical model. The results were combined with field survey on Caxias and other coastal areas of Portugal and Japan. The new calculations show the low ground areas up to 6 m in height area inundated by the tsunami. However, with the new proposal DEM the tsunami inundation is restricted to the beaches. The proposal includes the construction of a new sea wall with 7 m in height at Caxias beach, the increase in height of the Barcarena Stream levees and the elevation of the sidewalk at São Bruno beach, with a gentle slope up to 7 m in height. It is also proposed the construction of a third bridge over the Barcarena Stream for pedestrian ranging from 5 to 7 m in height that will serve as a gate for the incoming tsunami waves.

The growing concerns about floods have highlighted the need for accurate and detailed precipitation data as extreme precipitation occurrences can lead to catastrophic floods, resulting in significant economic losses and casualties. Integrated Multi-satellitE Retrievals for the Global Precipitation Measurement (GPM-IMERG) is a commonly used high-resolution gridded precipitation dataset and is recognized as trustworthy alternative sources of precipitation data. The aim of this study is to comprehensively evaluate the performance of GPM IMERG Early (IMERG-E), Late (IMERG-L), and Run Final (IMERG-F) in precipitation estimation and their capability in detecting extreme rainfall indices over southwestern Iran during 2001-2020. The Asfezari gridded precipitation data which are developed using a dense of ground-based observation were utilized as the reference dataset. The findings indicate that the IMERG-F performs reasonably well in capturing many extreme precipitation events (defined by various indices). All the three products showed a better performance in capturing fixed and non-threshold precipitation indices across the study region. The findings also revealed that both IMERG-E and IMERG-L have problems in rainfall estimation over elevated areas showing values of overestimations. Examining the effect of land cover type on the accuracy of the precipitation products suggest that both IMERG-E and IMERG-L show large and highly unrealistic overestimations over inland water bodies and permanent wetlands. The results of the current study highlight the potential of IMERG-F as a valuable source of data for precipitation monitoring in the region.

Abstract Objective: To assess wound infiltration with ropivacaine plus magnesium sulfate for pain relief following thyroid surgery. Background: Analgesia with local anesthetics following surgery is a critical element of alleviating postoperative pain. However, such strategies in neck surgery has not been a well-established practice. Methods: This prospective double-blind randomized study enrolled 68 patients who underwent thyroid surgery. Concerning the solution used for surgical wound infiltration the study participants were randomly allocated into three groups: 1) 100 mg of ropivacaine (Group R), 2) 100mg of ropivacaine plus magnesium sulfate 10mg/kg (Group RMg), and 3) normal saline which served as placebo (Group P). Pain perception both at rest and at movement, was measured using the Visual Analogue Scale (VAS) at 30 minutes, as well as 1, 2, 4, 6, 12, and 24 hours postoperatively. The total consumption of analgesics in morphine equivalents was also recorded. Moreover, adverse effects and patient satisfaction were recorded. Cortisol, TNF-α, and IL-6 levels were measured 30 minutes before infiltration, 6 hours and 24 hours postoperatively. Results: Demographics and clinical characteristics were similar between the groups. The VAS scores at rest and during movement were significantly lower in the RMg group compared to saline or ropivacaine groups. Total analgesic consumption was also significantly lower in the RMg group. No operational, wound or infiltration-related adverse effects were recorded in the study groups. Better overall satisfaction was obtained for the group RMg. Conclusions: Ropivacaine plus magnesium sulfate wound infiltration provided better pain control and analgesic effect was more significant, contributing to effective postoperative analgesia in patients undergoing thyroid surgery.

According to Indonesia’s result of Basic Health Research of 2013, prevalence of acute respiratory infection in 2007 and 2013 were not different (25.5% and 25.0%, respectively). Identifying the cause of acute pharyngitis is a key point in determining the optimal treatment. The main purpose is to evaluate the rational use of drugs and its irrational impact as well as the correlation of the drug use with the incidence and prevalence of acute pharyngitis. This study was a descriptive and observational study, carried out retrospectively and concurrently at two community health centers located in Bandung and Cimahi, Indonesia. There were 80.01% over prescription of antibiotics, with a total of 8.98% is non-treatment option, and 62.43% irrational used of corticosteroids. The incidence and prevalence of acute pharyngitis at one health center in Bandung were 2.45% and 2.31%, respectively, with irrationality rate of 83.82%. Those recorded at one health center in Cimahi were 2.11% of incidence and 2.00% of prevalence with irrational rate of 91.29%. It can be concluded that there were still irrational use of medicines in the treatment of acute pharyngitis in community health center. The higher incidence and prevalence might indicate the declining health services quality.

Telomeres, located at the ends of each chromosome play a vital role in determining cellular fate and aging. Accelerated shortening of telomeres may also result in accelerated aging and occurrence of age-related degenerative diseases. Anti-aging treatments may help in increasing the telomere length along with improving quality of life, reducing dependency for daily life activities, increasing life expectancy and reducing the risks associated with aging. In this study, we evaluated the effect of anti-aging integrative therapy in 36 individuals. The treatment included a combination of HBOT, ozone therapy, colon hydrotherapy, etc. Telomere length was used as a biomarker for objectively quantifying the outcome of the treatment. The effect of treatment was also assessed on various aging symptoms. At the end of the treatment, it was found that that 97.22% individuals showed an increase in telomere length with an average increase of 0.43 Kbp and 94.44% individuals showed reduced biological age with an average decrease of 3.8 years. These improvements were statistically significant. Improvements were also recorded in the majority of the symptoms. No major adverse events were observed. These results indicate that antiaging integrative therapy has the potential to reverse aging symptoms, cellular aging and improve quality of life.

Abstract: Giant Cell Arteritis (GCA) is an autoimmune/autoinflammatory disease affecting large vessels in patients over 50 years old. The disease presents as an acute inflammatory response with two phenotypes, cranial-GCA and Large Vessel Vasculitis (LV)-GCA, involving the thoracic aor-ta and its branches. 18F-fluorodeoxyglucose positron emission tomography-computed tomogra-phy (18F-FDG PET-CT) is among the imaging techniques contributing to diagnosis of patients with systemic disease. However, its association with soluble inflammatory markers is still elu-sive. This proof-of-concept study aims to identify novel soluble serum biomarkers in PET/CT pos-itive patients with LV-GCA and associate them with active (0 months) and inactive disease (6 months following treatment), in sequential samples. The Most-Disease-Segment Target-to-Background Ratio (TBRMDS) was calculated for 9 LV-GCA patients, while 12 cranial-GCA and 7 Polymyalgia Rheumatica patients with negative initial PET/CT served as disease controls. Serum macrophage-related cytokines were evaluated by Cytometric Bead Array (CBA). Finally, previously published NMR-metabolomics data acquired at the same blood sampling were associated with PET/CT findings. TBRMDS was significantly increased in active versus inactive disease (3.45 vs. 2.55, p=0.008). The analysis identified 6 serum metabolites, as more sensitive to change from the active to inactive state. Among them, choline levels were exclusively altered in the LV-GCA group, but not the disease controls. Cytokine levels were not associated with PET/CT activity. Combining with CRP, ESR, and TBRMDS a composite index was generated to depict well the differences between active and inactive systemic LV-GCA (25.45 vs 11.45, p=0.0039). These preliminary results could pave the way for more extensive studies integrating serum metabolomic parameters with PET/CT imaging data to extract sensitive composite disease indexes useful for the everyday clinical practice.

The concept of economic self-reliance, widely known by Thai people as the philosophy of sufficiency economy, has been widely promoted in rural Thai societies. By practicing this philosophy, it is expected that the citizens’ quality of life and local environments could be sustainably improved. This study aims to explore the contribution of the community practices of the sufficiency economy philosophy to rural villagers’ quality of life improvement, and to investigate potential factors that determine the trust of villagers in the philosophy. With the purpose to propose strategies which could enhance trust and promote villagers’ practices of the philosophy, the study investigated influences of three relevant factors on trust towards the philosophy. Those factors included factors related to cognitive-based trust, factors related to emotional-based trust, and factors related to demographic characteristics. Questionnaire surveys and in-depth interviews with community leaders and local villagers were conducted in the Ban Jamrung community, in Thailand’s Rayong province. The results of the statistical analysis revealed that the residents who applied the sufficiency economy philosophy in their daily lives experienced a relatively better quality of life. Additionally, it was found that trust in the philosophy could be predicted more by rational factors than by emotional factors. These findings could be utilized to develop strategies to maintain and enhance the trust of the people in the philosophy of sufficiency economy.

Neuroblastoma (NB) is a childhood cancer with heterogeneous characteristics, posing challenges to effective treatment. NBs express somatostatin receptors that facilitates the use of somatostatin analogs (SSTAs) as tumor-seeking agents for diagnosis and therapy. High-risk (HR) NBs often have gain-of-function mutations in the receptor tyrosine kinase anaplastic lymphoma kinase (ALK). Despite intensive multimodal treatment, survival rates remain below 40% for children with HR-NB. The aim of this work was to investigate the combined effect of the SSTA 177Lu-octreotide with the ALK inhibitor lorlatinib. Mice bearing human HR-NB CLB-BAR tumors were treated with lorlatinib, 177Lu-octreotide, combination of these pharmaceuticals or saline (control). Tumor volume was monitored and tumor samples were evaluated for cleaved caspase-3 and expression of 84 human genes involved in apoptosis. Combination treatment with 177Lu-octreotide and lorlatinib demonstrated synergistic antitumor effects. Increased number of cleaved caspase 3-positive cells was observed in tumors from mice treated with 177Lu-octreotide alone and in combination with lorlatinib. Modulation of Bcl-2 family gene expression was observed only in the presence of both 177Lu-octreotide and lorlatinib, with BID downregulated and HRK upregulated on days 2 and 7, respectively. The data suggests that ALK signaling pathway inhibition may contribute to radiosensitization in radionuclide therapy with 177Lu-octreotide.

Carbon tax policies (CTP) are globally acknowledged for curbing energy consumption and emissions. Despite global adoption, China's reluctance to embrace a carbon tax, possibly due to effectiveness and public acceptance concerns, is notable. This study employs Choice-Based Conjoint Analysis to gauge Shanghai residents' preferences on four CTP attributes. Among Shanghai's populace, the annual cost of the carbon tax policy ranks highest (48.87%), followed by implementation transparency (24.72%), revenue utilization (16.68%), and policy implementers (9.73%). Notably, Shanghai residents exhibit an average annual willingness to pay of 1435.28 CNY, indicating increased acceptance. Enhanced public awareness of carbon tax policies significantly boosts willingness to pay, augmenting carbon tax revenues and fostering low-carbon technology development. Additionally, transparency improvements in carbon tax policy yield notable increases in willingness to pay, underscoring the link between understanding CTP and its perceived importance. These findings highlight the potential of carbon tax policies in advancing sustainability and transitioning to low-carbon economies.

(1) Background: donor-derived circulating free DNA (dd-cfDNA) is an innovative biomarker with great potential for the early identification and prevention of graft damage; (2) Methods: Prospective study to analyze dd-cfDNA plasma levels in 30 kidney transplant patients during their post-transplant follow-up (15 days, 3, 6 and 9 months), to determine if the result could be of interest in the identification of possible adverse events, specially allograft rejection. In addition, the aim is also to verify the obtained data on sensitivity, specificity, NPV and PPV; (3) Results: Plasma levels of dd-cfDNA could be considered a novel biomarker of graft rejection after first term post-transplant up to several months before its clinical presentation, mainly in TCMR or ABMR. In this study, it appears to have no positive predictive value for borderline rejection or TCMR IA. Our results show a low NPV of the technique because other pathologies or biological post-transplant complications can also affect dd-cfDNA levels and they must be considered in the interpretation of the result.; (4) Conclusions: dd cfDNA could allow, together with other additional biomarkers in the context of a future score, avoid invasive biopsies in most cases, mainly in the case of suspected TCMR or ABMR.

Litsea martabanica root's antioxidant and AChE activity showed promise as a pesticide detoxification agent in our previous study. In addition to roots, its leaves can help mitigate pesticide exposure, although there is limited scientific evidence supporting their efficacy. However, the use of roots in many countries, such as Thailand, could contribute to environmental degradation, as highland communities traditionally cut down whole trees to obtain them. This study aims to evaluate the antioxidant activity and anti-pesticide potential of water extracts from L. martabanica leaves instead of its roots through in vitro and in vivo investigations. The findings showed that L. martabanica water extracts and fractions demonstrated varied antioxidant activity. The water extract, obtained using traditional extraction methods, was chosen for in vivo experiments. Rats received the extract followed by chlorpyrifos exposure for 16 days. Results indicated reduced acetylcholinesterase activity in chlorpyrifos-exposed rats, while treatment with leaf extract led to increased activity, suggesting its potential as a detoxifying agent. Histopathological examination revealed no liver cell necrosis and showed liver cell regeneration, indicating potential protection against free radical-induced liver damage without affecting rat liver weight or biochemical profiles. Utilizing L. martabanica leaves for healthcare purposes holds promise without negative environmental impact.

The aim was to evaluate the agreement between plaque detection with intraoral scanner system (IOS) and a conventional clinical method and to evaluate the inter-rater reliability for scoring 3D models with and without a disclosing agent. 14 participants were recruited from the Department of Operative Dentistry, School of Dentistry, University name blinded to reviewers, it is completed after the reviewing process. Participants eligible for inclusion were adults with good general health and a minimum of 20 teeth. Participants were clinically examined with plaque assessment according to the modified Quigley-Hein plaque index before and after using a disclosing agent (GC-Tri Plaque ID-Gel, GC). Before and after the application of the disclosing agent, all study participants were scanned using the IOS (TRIOS5, 3Shape TRIOS A/S). The clinical examiner and additional three examiners blinded to the clinical examination assessed plaque status on the acquired 3D models with and without disclosing agent using the same index to evaluate the inter-rater agreement. Intraclass coefficient correlation, one sample t-test and Cronbach’s α for inter-rater reliability were calculated. All methods showed moderate to strong correlations (Spearman’s rho ranging from 0.527 to 0.618) and Cronbach’s α ranged from 0.551 to 0.766. Level of agreement between con-ventional clinical registration and registration from 3D models was acceptable overall.

There is a growing trend among consumers to seek out natural foods and products with natural ingredients. This shift in consumer preferences had a direct impact on both food and pharmaceutical industries, leading to a focus of scientific research and commercial efforts to meet these new demands. The aim of this work is to review recent available scientific data on foods of interest, such as artichoke, gooseberry, and polygonoideae plants, as well as olive oil and red raspberries. Interestingly, the urgency of solutions to the climate change emergency has brought new attention to by-products of grapevine bunch stem and cane, which have been found to contain bioactive compounds with potential health benefits. There is a pressing need for a faster process of translating scientific knowledge from the laboratory to real-world applications, especially in the face of the increasing societal burden associated to non-communicable diseases (NCDs), environmental crises, the post-pandemic world, and ongoing violent conflicts around the world.

Construction using earth materials demonstrates ecological sustainability using locally sourced natural materials and environmentally friendly demolition methods. In this study, the environmental impact of adding cement to soil materials for rammed-earth farmhouse construction in rural China was investigated and comparatively simulated using the One Click LCA database, focusing on the conflict between sustainability objectives and the practical aspects of cement addition. By analyzing how the addition of cement aligns with local construction practices and by addressing the debate surrounding the inclusion of cement in rammed earth construction, our objective is to provide insights into achieving a balance between the environmental impact and the pragmatic considerations of using cement in earthen building practices. Three local structure scenarios are evaluated via simulations: a cement-stabilized rammed earth wall, a fired brick wall, and a localized reinforced concrete frame structure. The quantitative environmental impacts are assessed, and the qualitative differences in adaptation, economic sustainability, and other factors are examined in the context of present-day development in rural China. The results show that the use of cement-stabilized rammed earth wall-supported structures is associated with higher embodied carbon emissions compared to structures supported by reinforced concrete frames and enclosed by brick walls; however, these emissions are lower than those for brick wall-supported structures, while effectively meeting the structural requirements. In addition, the use of cement-stabilized earth for perimeter walls simplifies material management and disposal throughout the building's life cycle, and the cost-effectiveness of cement has been found to be substantially greater than that of reinforced concrete frames and brick structures, improving economic viability and social acceptability, especially among low-income communities in rural areas.

Today's city needs more than ever methodological devices that ensure a specific urbanism, in keeping with the complexity of relationships that occur in the urban space. Networks or systems of diverse nature must be activated to achieve a certain success of the city, even more so in its fragile central fabrics. The study is focused on the historic neighborhoods of the city of Jaén (Spain), which have a high vulnerability index. The aim is to establish a strategy to revitalize their urban and social capital and improve their articulation with the rest of the urban and territorial structure. A methodological proposal for the analysis of vulnerability factors and an urban and cartographic analysis of the public space is addressed through an interweaving of a triple network: environmental, social, and urban. For this purpose, the configuration of this overlapping network of analysis and formulation of criteria is presented, which considers the urban multiplicity and promotes new dynamics for the integrated urban regeneration of the area and for the activation of public and collective urban spaces.

Purpose: To report a novel application of excimer ablation for normalization of central corneal refractive irregularity, combined with higher fluence CXL in the effective management and visual rehabilitation of progressive keratoconus. Methods: 17 cases with progressive keratoconus were treated with a corneal surface excimer laser ablation normalization using the topographyguided (Contura) myopic ablation for customized corneal re-shaping using a 6mm optical zone. The epithelial removal was accounted for by adding a -2.75 diopters correction in the topographyguided normalizing surface ablation followed by, a second, wavefront-optimized hyperopic excimer treatment of + 2.75 diopters at 6mm optical zone. The 2 sequential excimer ablations were followed by the corneal crosslinking (CXL). Visual acuity, refraction, and keratoconus documentation via keratometry, topography, and pachymetry, as well as endothelial cell density were evaluated over 36 months. Results: Keratoconus stabilized in all cases. The severity of keratoconus stage by Amsler-Krumeich criteria improved for the OD from an average 2.2 to 1. Mean UDVA showed marked improvement at one-year follow-up all values in decimal: from 0.21±0.18 pre-operative to 0.51±0.25 at 12 months, with small additional improvement through the 3 years to 0.51±0.16. CDVA respectively increased from 0.55±0.11 to 0.77±0.14 at 1 year, and to 0.79±0.16 at 3 years. Mean minimal corneal thickness decreased significantly from 466.74±34.25 µm to 396.17±45.17 µm (P<.01) as recorded the first year postoperatively and then slightly increased to 405.17±32.21 µm at the 3-year follow-up. Conclusions: We introduce herein initial clinical data with the use of novel, off-label therapeutic excimer laser surface ablation application: Designed to perform both epithelial removal and anterior corneal stroma reshaping, to be combined with CXL, in order to apply the Athens Protocol CXL with US excimer laser approved specifications.

Alzheimer's disease (AD) is a neurodegenerative olfactory disorder affecting millions of people worldwide. Alterations in the hexosamine or glucose-related pathways have been described through AD progression. Specifically, an alteration in glucosamine 6 phosphate isomerase 2 (GNPDA2) protein levels has been observed in olfactory areas from AD subjects. However, the biological role of GNPDA2 in neurodegeneration remains unknown. Using mass-spectrometry, multiple GNPDA2 interactors were identified in human nasal epithelial cells (NECs) mainly involved in intraciliary transport. Moreover, GNPDA2 overexpression induced an increment in NEC proliferation rates, accompanied by transcriptomic alterations in Type II interferon signalling or cellular stress responses. In contrast, the presence of beta-amyloid or mutated Tau-P301L in GNPDA2-overexpressing NECs induced a slow-down in the proliferative capacity in parallel with a disruption in protein processing. The proteomic characterization of Tau-P301L transgenic zebrafish embryos demonstrated that GNPDA2 overexpression interfered with collagen biosynthesis and RNA/protein processing, without inducing additional changes in axonal outgrowth defects nor neuronal cell death. In humans, a significant increase in serum GNPDA2 levels was observed across multiple neurological proteinopathies (AD, Lewy body dementia, progressive supranuclear palsy, mixed-dementia, and amyotrophic lateral sclerosis) (n=187). These data shed new light on GNPDA2-dependent mechanisms associated to the neurodegenerative process beyond the hexosamine route.

Antimony (Sb) has gained significance as a critical raw material (CRM) within the European Union (EU) due to its strategic importance in various industrial sectors, particularly in the textile industry for flame retardants and as a component of Sb-based semiconductor materials. Moreover, Sb is emerging as a potential alternative for anodes used in lithium-ion batteries, a key element in the Energy transition. This study focused on exploring the feasibility of identifying and quantifying Sb mineralizations through the spectral signature of soils using reflectance spectroscopy, a non-invasive remote sensing technique, and by employing deep learning algorithms such as Convolutional Neural Networks (CNNs). Common signal preprocessing techniques were applied to the spectral data, and the soils were analyzed by Inductively Coupled Plasma Mass Spectrometry (ICP-MS). Despite achieving high R-squared values, the study faces a significant challenge of generalization of the model to new data. Despite the limitations, this study provides valuable insights into potential strategies for future research in this field.

Anticholinergic burden (ACB) from medications has been associated with adverse outcomes in older people. Aim: To conduct a non-randomised feasibility study of an intervention to Reduce anticholinerGic burdEN in oldER pATiEnts (REGENERATE) to inform a subsequent definitive trial. Methods: The development and evaluation of an ACB reduction intervention was guided by the Medical Research Council framework. Findings from preliminary studies, two systematic reviews and two qualitative studies informed the design of a mixed-method feasibility study. The study was conducted in one UK primary care site. The clinical pharmacist identified and invited potentially eligible patients, reviewed their medications and made recommendations to reduce the ACB as needed. Patients completed surveys at baseline, and 6- and 12- weeks post intervention. A purposive sample of patients and healthcare professionals was interviewed. Results: There was an 16/20 response; 14/16 attended the pharmacist led consultation and completed the baseline questionnaire and 13/14 completed both follow-up questionnaire. The sustainability of deprescribing was confirmed. The results suggest the potential of the intervention to reduce side effects from medications and improve quality of life (EQ-5D-5L). The interviews showed patients were happy with the study processes, and the medication changes, and were satisfied with the pharmacist’s consultation. Conclusions: This feasibility study demonstrated that a deprescribing/reducing ACB intervention in older people is feasible in a primary care setting and may benefit patients. Well-designed RCTs and cost-effectiveness studies should be undertaken to confirm the benefits of ACB deprescribing in primary care settings. Trial registration: ClinicalTrials.gov no. NCT04660838

Background and Objectives: In this current state, Type 2 Diabetes Mellitus (T2DM) is more prevalent in the population, and metformin is used as a first-line medication for treating it. There was up surge in the utilization of alternative therapies in the management of diabetes. Especially in diabetes, Herbal medicines are considered safe and reliable by majority of the population. Aim: The purpose of this research is aimed to estimate the safety and efficacy of Polyherbal Metabolite Compounds (PHMC) capsules in adults with T2DM. Materials and Methods: In this study, 60 T2DM patients aged 18-60 years were randomly assigned to Groups A (30) receiving Metformin 500 mg twice a day after food and Group B (30) receiving PHMC capsule 500 mg twice a day after food in a prospective, randomized and open-label clinical study. The in-silico simulation study was performed to selected plants major compounds on target protein Insulin-like Growth Factor-1 (1K3A). Result: The PHMC is found to be safe and effective in the management of T2DM. The FBS, PPBS and HbA1c were significantly lowered (p

Acoustic Radiation Forced Impulse (ARFI) is an ultrasound integrated method, measuring stiff-ness by point shear wave elastography. To evaluate the diagnostic performance of ARFI of the liver and of the spleen, combined with spleen dimension and platelet count, in predicting clinical events in cirrhosis, a prospective and cross-sectional study was conducted between February 2017 and February 2021. The following ratio scores with ARFI measurements were performed: ALSDP (ARFI Liver-Spleen Diameter-to-Platelets ratio score), ASSDP (ARFI Spleen-Spleen Diam-eter-to-Platelets ratio score), ASSAP (ARFI Spleen-Spleen Area-to-Platelets ratio score), ALSAP (ARFI Liver-Spleen Area-to-Platelets ratio score). In 100 enrolled subjects, spleen ARFI, ASSDP, ASSAP, were significantly associated with high-risk oesophageal varices (HRVs) in the prospec-tive short- and long-term follow-up and in the cross-sectional study (p 0.7). ARFI-ratio scores can predict, in cirrhotic patients, the risk of developing HVRs in short and long-term period.

Neurodegeneration is a major problem in neuroscience and medicine as it causes and worsens many neurological and psychiatric disorders. It involves gradual loss of neurons at different levels of the brain, affecting cognition, emotion, behavior, consciousness, and attention. Understanding the causes and consequences of neurodegeneration is crucial for identifying the risk factors, biomarkers, and treatments. However, the current therapies are mostly symptomatic and ineffective. Therefore, new and innovative methods, such as noninvasive brain stimulation (NIBS), are needed to modulate brain activity and plasticity in a safe and reversible manner. This field is rapidly developing, with a focus on exploring new clinical applications, mechanisms, and combinations of NIBS and drugs. This special issue covers the latest progress and challenges in the study of neurodegeneration in cognitive impairment and mood disorders from the experimental, clinical, and translational perspectives. It addresses the complexity and diversity of these conditions, the lack of disease-modifying treatments, the ethical and practical issues of conducting research in vulnerable and diverse populations, the integration and interpretation of data from multiple sources and modalities, and the development and validation of novel methods such as NIBS, artificial intelligence, and drug repurposing. Collaborative efforts among various stakeholders are needed to improve our knowledge and treatment of neurodegeneration underlying cognitive impairment and mood disorders.

The mutation in NF2 is the most common alteration associated with meningioma oncogenesis, and it is related to the loss of a suppressing protein called merlin. At the same time, alterations in energy production are visible in cancer cells where increased demand for energy is observed. Fatty acid oxidation could be one of the ways cancer cells obtain energy. This metabolic pathway uses the acylcarnitine shuttle system, which is responsible for the acylation of fatty acids and their transport through mitochondria. Therefore, this study aimed to profile acylcarnitines with short-, medium- and long-acyl chain length in meningiomas to assess their changes in tumors with different NF2 mutation statuses. For the analysis, solid-phase microextraction (SPME) coupled with liquid chromatography high resolution mass spectrometry (LC-HRMS) was used. The presented sampling method enables low invasive and easy collection of the analytes from the studied lesions, which can be crucial for future analysis of potential biomarkers in the surgery room. It was observed that higher levels of these analytes characterized meningiomas with NF2 mutation. Moreover, increased energy consumption and elevated levels of acylcarnitines show that these analytes can be considered as a marker of increased fatty acid oxidation in NF2 mutated cells.

BackgroundLiving donor liver transplantation offers comparable long-term results to cadaveric donor transplantation. This study analyzes the selection process of living liver donors at a Western transplant center that utilizes both donation forms. MethodsThis retrospective analysis examined potential living donors, collecting medical data and reasons for refusal, and divided patients by indication and urgency for transplantation. ResultsFrom January 2013 to December 2023, 594 potential living donors were assessed at Jena University Hospital. Of these, 124 living donor transplants were performed. During outpatient evaluation, 357 potential donors were excluded. Subsequently, 238 individuals underwent inpatient assessment, with 100 more being excluded. Main reasons for donor refusal included medical or psychological issues (n=160), disease progression in recipients (n=90), and recipient refusal or donor withdrawal (n=54). The evaluation process showed a trend towards considering more distant relatives and acquaintances as donor candidates with increasing severity of the recipient's disease.

Multifunctional landscapes are complex systems that integrate biophysical, cultural-historical and socio-economic components into unique territorial structures and regional ensembles. Facing increasing pressures generated by urbanization, climate change and overexploitation of natural resources, assessing the sustainability of these landscapes has become an urgent priority. The present research is based on the development and parametrization of a new tool for evaluating the sustainability of multifunctional landscapes that aims to measure the level of biocultural resilience of a landscape, integrating biological, cultural and socio-economic indicators in a single analytical framework. This index, called the biocultural resilience index (BRI), provides a holistic perspective on the dynamics of landscapes, allowing the identification of vulnerability areas and the development of conservation and sustainable management strategies. The evaluation of the of multifunctional landscapes sustainability requires a comprehensive approach that has to integrate both biological aspects, such as biodiversity and ecosystem health, as well as identity and cultural aspects, such as cultural value and the relationship of the local communities with the environment. In this context, this study highlights the fact that the development of appropriate tools and methods for assessing and monitoring the sustainability of multifunctional landscapes becomes essential for their sustainable management and for protecting the benefits they offer to society. Our findings show that the biocultural resilience index (BRI) can be used in a variety of contexts and fields, including spatial planning, biodiversity conservation, sustainable rural development and ecotourism. In the meanwhile, this index offers a robust and flexible analytical framework, adaptable to the needs and particularities of different regions and communities.

Clinical academics experience dual workplaces; the clinical and the research environment. However, working in two workplaces leads to difficulty in forming an integrated identity, and hence affects a person’s work environment and well-being. The aim was to explore how clinical academics experience the psychosocial work environment and their suggestions for improving and changing work well-being. A multicenter qualitative approach with group interviews inspired by participatory action de-sign was used. A purposeful criterion sampling strategy was used, selecting researchers affiliat-ed with the university's research network (n=12). Data were analyzed by thematic analysis and the consolidated criteria for reporting qualitative research was applied. The main finding “lack of integration of research in clinical practice”, revealed how clinical academics balanced between the two practices, how their need for belonging in both work environments were established by fellowship, and how motivational factors and role models could be enhanced through a joint commitment of responsibility in research units and clinical practice. This study provides a contemporary understanding of the challenges that clinical academics en-counter and what solutions they would offer. This study adds to knowledge on psychological work well-being and provides solutions on how clinical academics can achieve integration of research in clinical practice.

Systematic reviews represent a powerful instrument to summarize the existing evidence in medical literature. However, articles for a systematic review are hard to identify, and mostly require a structured search of the literature through a number of databases, using keyword-based search strategies, followed by the painstaking manual selection of pieces of evidence that are pertinent to the query. A.I. algorithms may offer solutions to reduce the workload on investigators. We applied BERTopic, a newer and much-recognized transformer-based topic-modeling algorithm, to two datasets of 6137 and 5309 articles of newly published systematic reviews in the area of peri-implantitis and bone regeneration in implant dentistry. In the two datasets, BERTopic identified 14 and 22 clusters, respectively, and it automatically created labels describing the nature of the topics for each individual cluster based on semantic interpretation of their titles. Most themes regarded the query theme, but in both conditions, BERTopic also uncovered articles related to off-themes, which composed around 30% of the dataset—with sensitivity up to 0.79 and specificities of at least 0.99. Our results suggest that adding a topic-modeling step to the screening process could potentially save working hours for researchers involved in systematic reviews of the literature.

The objective of this study was to detail the monomer composition of resin-based dental materials sold in the market in 2023 and to evaluate the proportion of BPA derivatives in relation with their applications. A search on manufacturers’ websites was performed to reference resin-based dental materials currently on the market. Their monomer composition was determined from material safety data sheets and completed with a search on PubMed database. Among the 543 material compositions exploitable, 382 (70.3%) contained BPA derivatives. Among them, 56.2% contained BisGMA, 28% BisEMA, the most frequently reported. A total of 59 monomers of which 6 BPA-derivatives were found. 309 materials (56.9%) contained UDMA and 292 (53.8%) TEGDMA. Less than one third of materials identified contained no BPA derivatives. These proportions vary a lot depending on their applications with materials dedicated to dental care of young populations containing the highest proportions of BPA-derivatives monomers. The long-term effects on human health of the different monomers identified including BPA-derivatives monomers is a source of concern. For children and pregnant or lactating women arises the question to take a precautionary principle and avoid the use of resin-based dental materials likely to release BPA by opting for alternative materials.

Acute and chronic respiratory diseases impose a significant economic and health burden. Distal small airway assessment requires invasive procedures such as a bronchoscopy and bronchoalveolar lavage. The Particles in Exhaled Air (PExA) device provides a non-invasive means of assessing small airways; it captures distal airway particles sized around 0.5-7m and contains particles of respiratory tract lining fluid (RTLF) that originate during airway closure and opening. The PExA device can measure particle count and mass according to particle size. Subsequent capture of particles in a thin membrane enables application of various analytical methods to assess a broad range of biomolecules including phospholipids, proteins, inflammatory profile, and other metabolites to characterise inflammation and diseases processes such as asthma, chronic obstructive pulmonary disease, acute respiratory distress syndrome, lung cancer, and more recently acute infections such as COVID-19. PExA analysis provides a promising alternative to traditional investigative methods in the assessment, diagnosis, and management of respiratory conditions. By evaluating specific biomarkers in the RTLF associated with airway inflammation, PExA may offer a more accurate and comprehensive understanding of the molecular-level changes in the small airways of patients with acute and chronic lung diseases.

Lifestyle interventions can prevent type 2 diabetes (T2DM). However, some in-dividuals do not experience anticipated improvements despite weight loss. Bi-omarkers to identify such individuals at early stages are lacking. IGF-1 and IGFBP-1 were shown to predict T2DM onset in prediabetes. We assessed if these markers also predict the success of lifestyle interventions, thereby possibly guid-ing personalized strategies. We analyzed fasting serum levels of IGF-1, IGFBP-1 and IGFBP-2 in relation to changes in metabolic and anthropometric parameters, including intrahepatic li-pids (IHL) and visceral adipose tissue (VAT) volume measured by MRI, in 345 high-risk prediabetic participants (54% female; aged 36-80 years). Participants were enrolled in three randomized dietary intervention trials and assessed both at baseline and one year post-intervention. Statistical analyses were performed using IBM SPSS Statistics (version 28), significance set at p

Background: Dietary quality and the consumption of antioxidant-rich foods has been shown to protect against memory decline. Therefore, this double-blind, randomized, placebo-controlled study aimed to investigate the effects of a nutritional supplement on changes in cognitive performance. Methods: In adults aged 40 to 70 years with subjective memory complaints, participants were randomly allocated to take a supplement containing vitamin E, astaxanthin, and grape juice extract daily for 12 weeks or a matching placebo. The primary outcomes comprised changes in cognitive tasks assessing episodic memory, working memory, and verbal memory. Secondary and exploratory measures included changes in the speed of information processing, attention, and self-report measures of memory, stress, and eye and skin health. Moreover, changes in plasma concentrations of brain-derived neurotrophic factor, malondialdehyde, tumor-necrosis factor-α, and interleukin-6 were measured, along with changes in skin carotenoid concentrations. Results: compared to the placebo, nutritional supplementation was associated with larger improvements in episodic memory, a self-report measure of everyday memory, increased plasma brain-derived neurotrophic factor, decreased plasma malondialdehyde, and increased skin carotenoid concentrations. However, there were no group differences in changes in the remaining outcome measures. Conclusions: Twelve weeks of supplementation with a nutritional supplement was associated with improvements in episodic memory and several biological markers associated with cognitive health. Future research will be essential to extend and validate the current findings.

Gastric cancer is the 5th most common disease in the world and the 4th most common cause of death. It is diagnosed through esophagogastroduodenoscopy with biopsy, however there are limitations in finding lesions in the early stages. Recently, research has been actively conducted to use liquid biopsy to diagnose various cancers, including gastric cancer. Various substances derived from cancer are reflected in the blood. By analyzing these substances, it was expected that not only the presence or absence of cancer but also the type of cancer can be diagnosed. However, the amount of these substances is extremely small, and even these have various variables depending on the characteristics of the individual or the characteristics of the cancer. To overcome these, we collected methylated DNA fragments using MeDIP and compared them with normal plasma to characterize gastric cancer tissue or patient’s plasma. And we attempted to diagnose gastric cancer using the characteristics of cancer reflected in the blood through the cancer tissue and patient’s plasma. As a result, we confirmed that the consistency of common methylated fragments between tissue and plasma was approximately 41.2%, and found the possibility of diagnosing and characterizing cancer using the characteristics of the fragments through SFR and 5'end-motif analysis.

Dye-based angiography is the main imaging modality in evaluating the vasculature of the eye. Although most commonly used to assess retinal vasculature, it can also delineate normal and abnormal blood vessels in the anterior segment diseases – but is limited due to its invasive, time-consuming methods. Thus, anterior segment optical coherence tomography angiography (AS-OCTA) is a useful non-invasive modality capable of producing high-resolution images to evaluate the cornea and ocular surface vasculature. AS-OCTA has demonstrated the potential to detect and delineate blood vessels in the anterior segment with quality images comparable to dye-based angiography. AS-OCTA has a diverse range of applications for the cornea and ocular surface, such as objective assessment of corneal neovascularization and response to various treatments; diagnosis and evaluation of ocular surface squamous neoplasia; and evaluation of ocular surface disease including limbal stem cell deficiency and ischemia. Our review aims to summarize the new developments and clinical applications of AS-OCTA for the cornea and ocular surface.

There are several well-described molecular mechanisms that influence cell growth and are relat-ed to the development of cancer. Chemokines constitute a fundamental element which are not only involved in local growth but also affect angiogenesis, tumor spread and metastatic disease. Among them, the C-X-C motif chemokine ligand 12 (CXCL12) and its specific receptor the chemo-kine C-X-C motif receptor 4 (CXCR4) have been widely studied. The overexpression in cell mem-branes of CXCR4 has been shown to be associated with the development of different kinds of his-tological malignancies, such as adenocarcinomas, epidermoid carcinomas, mesenchymal tumors or neuroendocrine neoplasms (NENs). The molecular synapsis between CXCL12 and CXCR4 leads to the interaction of G proteins and activation of different intracellular signaling pathways in both gastroenteropancreatic (GEP) and bronchopulmonary (BP) NENs conferring greater ca-pacity for locoregional aggressiveness, epithelial-mesenchymal transition (EMT) and the ap-pearance of metastases. Therefore, it has been hypothesized how to design tools that target this receptor. The aim of this review is to focus on current knowledge of the relationship between CXCR4 and NENs, with a special emphasis on diagnostic and therapeutic molecular targets.

Recombinant α1-microglobulin (A1M) is proposed as protector during 177Lu-octreotate treatment of neuroendocrine tumors, which is currently limited by bone marrow and renal toxicity. Co-administration of 177Lu-octreotate and A1M could result in a more effective treatment by protecting healthy tissue, but, the radioprotecting action of A1M is not fully understood. The aim of this study was to examine the proteomic response of kidneys and bone marrow early after 177Lu-octreotate and/or A1M administration. Mice were injected with 177Lu-octreotate and/or A1M, while control mice received saline or A1M vehicle solution. Bone marrow, kidney medulla, and kidney cortex were sampled after 24 hours or 7 days. Differential protein expression was analyzed with tandem mass spectrometry. Dosimetric estimation was based on 177Lu activity in kidney. PHLDA3 was the most prominent radiation responsive protein in kidney tissue. In general, no statistically significant difference in expression of radiation-related proteins was observed between the irradiated groups. Most canonical pathways were identified in bone marrow from the 177Lu-octreotate+A1M group. Altogether, tissue-dependent proteomic response followed exposure to 177Lu-octreotate alone or together with A1M. Combining 177Lu-octreotate with A1M did not inhibit the radiation induced protein expression early after exposure, and late effects should be further studied.

The DNA Damage Response (DDR) network and the mitogen-activated protein kinase (MAPK) signaling pathway are crucial mechanisms for the survival of all living beings. An accumulating body of evidence suggests that there is a crosstalk between these two systems, thus favoring the appropriate functioning of multi-cellular organisms. On the other hand, aberrations within these mechanisms are thought to play a vital role in the onset and progression of several diseases, including cancer, as well as in the emergence of drug resistance. Here, we provide an overview of the current knowledge regarding alterations in the DDR machinery and the MAPK signaling pathway, as well as abnormalities in the DDR-MAPK functional crosstalk in multiple myeloma, the second most common hematologic malignancy. We also present the latest advances in the development of anti-myeloma drugs targeting crucial DDR- and MAPK-associated molecular components. These data could potentially be exploited to discover new therapeutic targets and effective biomarkers, as well as for the design of novel clinical trials. Interestingly, they might provide a new approach to increase the efficacy of anti-myeloma therapy by combining drugs targeting the DDR network and the MAPK signaling pathway.

The resilience of towns and cities refers to their ability to adapt and recover when confronted with pressures or challenges. This study employs ten variables as indicators to assess the resilience of urban areas by analyzing official data and constructing a multilevel mixed-effects structural equation model. The empirical findings demonstrate that enhancing resilience significantly influ-ences urban service functions, such as strengthening healthcare systems, stabilizing the real estate market, and addressing socio-economic challenges. Specifically, factors such as healthcare re-sources, housing demand, population structure, and social security exhibit varying levels of resil-ience, which profoundly impact the spatial distribution of these factors and socio-economic de-velopment. Disparities in healthcare resource allocation, demographic aging trends, and shifts in the housing market closely correlate with resilience levels in different regions. Additionally, the study emphasizes that improving resilience not only boosts the reliability and security of urban services but also ensures that communities receive necessary support and protection during times of adversity. Consequently, policymakers should recognize the pivotal role of urban resilience in resource allocation and social equity, devising corresponding strategies to enhance the resilience of these areas.

Traditional seismic wave-based tunnel advanced geological forecasting techniques are primarily designed for drill and blast method construction tunnels. However, given the fast excavation speed and limited prediction space in Tunnel Boring Machine (TBM) construction tunnels, traditional methods have significant technical limitations. This paper analyzes the characteristics of different types of TBM construction tunnels and, considering the practical construction conditions, identifies an effective observation system and data acquisition method. Utilizing numerical simulation, a model for advanced detection of typical unfavorable geological formations is established by obtaining the wave field response characteristics of seismic waves in three-dimensional space. The seismic wave reflection method can effectively receive information from unfavorable geological formations in front of the tunnel face. To address the challenges in advanced forecasting for TBM construction tunnels, a method of ellipsoid positioning velocity analysis, which takes into account the constraints of three-component data directions, is proposed. Based on the characteristics of the advanced forecasting observation system, the method compares the maximum values on the spatial isochronous ellipsoidal surface to determine the average velocity of the geological layer rays, thereby enabling accurate inversion of the spatial distribution ahead. Field verification of advanced geological forecasting based on ellipsoid positioning velocity analysis for TBM tunnels is conducted. The results indicate that this method can be used to obtain the three-dimensional velocity of the predicted unfavorable geological formations in front of the tunnel and is effective for the application of geological forecasting in TBM construction tunnels, thus providing crucial references and assurances for construction.

This narrative review synthesizes recent basic and clinical research on visual disturbances in low-light environments, highlighting evaluation techniques for these conditions. It focuses on the degradation of visual acuity under dim lighting, exacerbated by pupil dilation, known as night vision disturbances (NVD). Key contributors to NVD include optical scattering, intraocular diffraction, ocular aberrations, and uncorrected refractive errors, all significantly impacting quality of life and functional abilities. The review also examines the effects of aging, eye disorders, surgical interventions, and corneal irregularities on NVD. It details the definitions, distinctions, and measurement methodologies for various optical phenomena, using both objective and subjective approaches, such as visual function questionnaires, simulators, and the Light Distortion Analyzer (LDA). The LDA is validated for clinical characterization and quantification of light distortion, proving useful in both clinical and research settings. The review advocates for continued innovation in therapeutic interventions to improve patient outcomes and alleviate the impact of visual disturbances.

Aims/Hypothesis): Type 1 diabetes is an immune-mediated disease with destruction of the pancreatic β-cells, a process that is conditioned by multiple genes and other factors. HLA counts as the major susceptibility gene. Significant variations in HLA genetic susceptibility to type 1 diabetes between Caucasians, African and Asian and other ethnic groups may have led to the variation in incidence of type 1 diabetes globally. Type 1 diabetes is characterized upon HLA identification. In this chapter we discuss global variations in genetic susceptibility of HLA with regard to type 1 diabetes globally with a particular attention to Arab population. Methods): Haplotype configuration of HLA class I A, B, C and Class II –DR/DQ/DP were studied in Caucasians, African and Asian and in Arab population to see if that is responsible for the exponential rise in the rate of type 1 diabetes. Results): Although Arabs have one of the highest global incidence and prevalence rates of type 1 diabetes, unfortunately, there is a dearth amount of information regarding HLA genetic susceptibility to type 1 diabetes in the Arab world. HLA haplotype configurations contribute to its risk value. However, out of an insufficient present study there are examples of misjudgment of HLA risk according to HLA alleles rather than haplotypes. Conclusion): To date HLA outlooks for the characterization of type 1 diabetes. There is an ethnicity difference in HLA characteristics which is responsible for variation in type 1 diabetes. Although Arab population have contributed heavily in the rise of burden of type 1 diabetes, however, there is significantly a dearth amount of studies on HLA in Arab population. Obviously, any future prediction, prevention or cure of the disease will be based on the HLA genetics. There is a dire need for a systematic screening of HLA for Arab population with type 1 diabetes, identification of Arab HLA-risk values and identify those who are prone to get the disease.

Severe inherited alpha-1 antitrypsin deficiency (AATD) is an autosomal genetic condition linked to chronic obstructive pulmonary disease (COPD). The significance of heterozygous, milder deficiency variants (Pi*M, Pi*S, Pi*Z) is less clear. We studied AATD genotypes in 145 children (up to 72 months old) with assessed wheezing severity using the Pediatric Respiratory Assessment Measure (BCCH PRAM score). A control group of 74 children without airway obstruction was included. AAT concentration and Pi phenotype were determined from dry blood spot samples using nephelometry and real-time PCR; PiS and PiZ alleles were identified by isoelectrofocusing. Among the wheezers, the Pi*S allele incidence was 2.07% (3 cases) and Pi*Z allele was 6.9% (10 cases). The Pi*Z allele frequency was higher in wheezers compared to controls (44.8% vs. 20.27%) and the general Lithuanian population (44.8% vs. 13.6%) and was similar to adult COPD patients in Lithuania: Pi*S 10.3% vs. 15.8% and Pi*Z 44.8% vs. 46.1%. No association was found between AAT genotypes and wheezing severity. Finding that wheezer children exhibit a frequency of Z* and S* alleles like that found in adults with COPD suggests a potential genetic predisposition that links early wheezing in children to the development of COPD in adulthood. Larger cohort studies are needed to confirm this finding.

D-dimer testing in combination with clinical assessment is commonly used to diagnose suspected DVT and pulmonary embolism. However, as D-dimer levels are physiologically higher in elderly patients, this test loses clinical specificity in the setting of geriatric patients. The aim of our study was to investigate the changes in D-dimer levels with age and the specificity of the D-dimer test in the diagnosis of pulmonary embolism. 1617 elderly patients consecutively admitted to the Geriatric Emergency Care Department of the INRCA-IRCCS hospital between January 2013 and February 2014 and for whom D-dimer results were available were included. The D-dimer immunoturbidimetric assay was performed on a cs-2100i Sysmex Siemens using a conventional cut-off level of 500 µg/L. The median D-dimer level was 1200 [550-2990] µg/L FEU, and the percentage of patients with D-dimer levels below the conventional cut-off was only 22.1%. As expected, there was a significant age-related increase in D-dimer, even when sex was considered, and a significant decrease in the specificity of D-dimer assay with age. The most established use of D-dimer testing is in the diagnosis of deep vein thrombosis or pulmonary embolism. Our study confirms the need for an age-adjusted cut-off for D-dimer testing in geriatric patients.

Familial pancreatic cancer (FPC) represents a significant yet underexplored area in pancreatic cancer research. Basic research efforts are notably limited, and when present, they are predominantly centered on BRCA1 and BRCA2 mutations due to the scarcity of other genetic variants associated with FPC, leading to a limited understanding of the broader genetic landscape of FPC. This review examines the current state of FPC research, focusing on the molecular mechanisms driving pancreatic ductal adenocarcinoma (PDAC) progression. It highlights the role of homologous recombination (HR) and its therapeutic exploitation via synthetic lethality with PARP inhibitors in BRCA1/2-deficient tumors. The review discusses various pre-clinical models of FPC, including conventional two-dimensional (2D) cell lines, patient-derived organoids (PDOs), patient-derived xenografts (PDXs), and genetically engineered mouse models (GEMMs) as well as new advancements in FPC research.

In Burkina Faso, there is lack of awareness of antibiotics use at community level. In this study, we generate information on the commonly used antibiotics along with the reasons for which they have been used, in rural Burkina Faso. The ‘drug bag’ method, was employed to collect information from 423 households, in the health district of Nanoro. Descriptive analyses were performed using R software version 4.2.1. The number of self-reported antibiotic use on a regular basis was estimated at 3401 of which amoxicillin was reported 367 times (10.8 %), oxytetracycline was reported 288 times (8.5 %), ampicillin, 245 times (7.2 %), metronidazole, 239 times (7 %), and norfloxacin 223 times (6.6 %). Among the health complaints for which amoxicillin was used, wounds accounted for 28.5% (88/309) and gastrointestinal disorders 17.1% (53/309). For oxytetracycline, gastrointestinal disorders accounted for 57.1% (121/212) and wounds 22.64% (48/212). The study highlights the use of antibiotics for a range of health problems within the community, as well as antibiotics that appeared to of importance in people’s life. Further research is essential to elucidating the rationalities and logic reasoning underlying such use of antibiotics.

Background: Land use and land cover change (LULCC) in the Ruhuhu River Sub-Basin (RRSB), a crucial watershed within the Lake Nyasa Basin in Tanzania, poses a significant threat to water resource sustainability and ecological integrity. However, a lack of comprehensive data on long-term LULCC trends has hindered effective conservation efforts. Methods: This study utilized Landsat 5 TM and Landsat 8 OLI data within Google Earth Engine to quantify LULCC dynamics from 1990 to 2023. Six land cover classes were analyzed: water, forest, barren land, grassland, shrubland, and farmland. Results: Results revealed a substantial decline in forest cover (56.92% to 28.60%), primarily converted to farmland (2.99% to 20.22%). Shrubland expanded initially but then declined, while barren land steadily increased. These changes have profound implications for water resources, biodiversity, and ecosystem services within the RRSB and the broader Lake Nyasa Basin. Conclusions: This research highlights the urgency of implementing sustainable land management practices to mitigate the adverse impacts of LULCC in the RRSB. The high classification accuracies achieved (90.9% to 98.7%) validate the robustness of the methodology. This study provides crucial insights for policymakers, land managers, and conservation practitioners, emphasizing the need for targeted interventions to promote sustainable land use and ensure the long-term resilience of the RRSB ecosystem.

Autosomal dominant polycystic kidney disease (ADPKD) is an inherited disorder characterized by renal tubular cystic dilatations. The cysts can develop anywhere along the nephron and over time the cystic dilatation lead to kidney enlargement. On the other hand, the cysts begin to reduce the number of functional nephrons as a consequence of cystic expansion that further contributes to the decline in renal function over the years. The pressure exerted by the dilated cysts lead to compensatory mechanisms that further contribute to the decline in renal function. These structural changes are responsible of glomerular hyperfiltration states, albuminuria, proteinuria, and haematuria. However, the presentation of ADPKD varies in children from a completely asymptomatic child with incidental ultrasound detection of cysts to a rapidly progressive disease. There have been reports of early onset of ADPKD in children younger than 2 years that showed a more rapid decline in renal function. ADPKD is caused by mutation in PKD1 and PKD2 genes. Today, the PKD1 gene mutation seems to account for up to 85% of the cases worldwide, and it is associated with worse renal outcomes. Individuals with PKD2 gene mutation seem to present a milder form of the disease, with a more delayed onset of end stage kidney disease. The cardinal sign of ADPKD is the presence of renal cysts during renal ultrasound. The current guidelines provide the clinicians the recommendations for genetic testing in children with a positive family history. Given that the vast majority of children with ADPKD present with normal or supra normal kidney function we explored the glomerular filtration rates dynamics and the renal ultrasound adjusted percentiles. 14 out of 16 patients had kidney percentile over 90%. The gene mutations were equally distributed among our cohort. In addition, we compared the modified Schwartz formula to the quadratic equation after adjusting the serum creatinine measurements. It seems that even though children with ADPKD have enlarged kidneys, the renal function is more likely normal or near normal when the quadratic estimation of glomerular filtration rate is used (qGFR tended to be lower, 111.95 ± 12.43 ml/min/1.73m2 compared to Schwartz eGFR 126.28 ± 33.07ml/min/1.73m2, p=0.14). Also, when the quadratic equation was employed, not even a patient reached the glomerular hyperfiltration thresholds. The quadratic formula showed that glomerular filtration rates are linear or slightly decreasing after 1-year of follow-up (Quadratic ΔeGFR=0.32±5.78ml/min/1.73m2) as opposed to Schwartz formula that can falsely classify children in a hyperfiltration state ΔeGFR=7.51±19.46ml/min/1.73m2), p=0.019.

Environmental, social, and governance (ESG) investment has become a common trend in capital markets, and many institutional investors have publicly declared their long-term ESG investment target (ESGIT). This study focuses on investors who conduct strategic asset allocation (SAA) using composite indices but establish their ESGIT outside the SAA process. A mismatch could arise between investors’ planned and actual portfolios because they must pursue their ESGIT by asset selection, which inevitably makes the constituents of their portfolios different from those of composite indices. To scrutinize the potential existence of a misalignment between their SAA and ESGIT, this study analyzes actual stock and bond indices over the past decade using traditional mean-variance optimization. The results reveal significant differences between the expected and realized performances, and the misalignment is more significant when the analysis period is divided into two sub-periods: stable and volatile. Specifically, the results indicate that the efficient frontier constructed using ESG indices significantly differs from that constructed using composite indices, and that the difference between these two efficient frontiers becomes more significant during volatile periods. Furthermore, the results show that investors cannot meet their targets if their ESGIT is established outside the SAA process.

More than 90% of patients affected by mastocytosis are characterized by a somatic point mutation of c-KIT, which induces ligand-independent activation of the receptor and downstream signal triggering, ultimately leading to mast cell proliferation and survival. The most frequent mutation is c-KIT p.D816V, but other rarer mutations can also be found. These mutations often have a very low variant allele frequency (VAF), well below the sensitivity of common next-generation sequencing (NGS) methods used in routine diagnostic panels. Highly sensitive methods are developing for detecting mutations. This review summarizes the current indications on the recommended methods and on how to manage and interpret molecular data for the diagnosis and follow-up of patients with mastocytosis.

Background: Contrast-induced acute kidney injury (CIAKI) is a common complication in hospital-acquired renal conditions, yet its pathogenesis remains unclear and effective treatments are limited. Intermedin (IMD), a peptide related to the calcitonin gene, exhibits vasodilatory and endothelial barrier-stabilizing effects via the calcitonin receptor-like receptor (CLR). However, the potential of IMD in mitigating CIAKI has not been thoroughly investigated. Aims: This study aimed to delineate the protective role of IMD in CIAKI through both in vitro and in vivo models, with a particular focus on elucidating the underlying mechanisms, specifically the cAMP/Rac1 signaling pathway. Methods: Human umbilical vein endothelial cells (HUVECs) were treated with iohexol to simulate kidney injury in vitro. The protective effects of IMD were evaluated using the CCK8 assay, flow cytometry, ELISA, and western blotting. A CIAKI rat model was developed to assess renal peritubular capillary endothelial cell injury and renal function using a range of techniques, including histopathology, immunohistochemistry, immunofluorescence, western blotting, and transmission electron microscopy. Results: In vitro, IMD significantly enhanced HUVEC viability and mitigated iohexol-induced toxicity by preserving intercellular adhesion junctions and activating the cAMP/Rac1 pathway. The protective effects of IMD were attenuated by Rac1 inhibition. In vivo, CIAKI caused considerable damage to peritubular capillary endothelial cell junctions, leading to impaired renal function. IMD treatment markedly improved renal function, an effect that was abolished by Rac1 inhibition. Conclusion: IMD protects against renal injury in CIAKI by activating the cAMP/Rac1 pathway, thereby preserving the integrity of peritubular capillary endothelial cells and mitigating acute renal injury induced by contrast media. These findings underscore the therapeutic potential of IMD in CIAKI and emphasize the critical role of the cAMP/Rac1 pathway in renal protection.

The genus Strophantus belongs to the Apocynaceae family of flowering plants which grows primarily in tropical Africa. The plants are widely used in traditional herbal medicine. S. sarmentosus, in particular, is used for the treatment of, e.g., joint pain and rheumatoid arthritis, wound infections, head lice, diarrhoea, snake bite, and eye conditions. Despite the widespread use, dedicated research characterizing bioactive plant components is scarce. Investigations focussed mainly on the cardenolides, because of their cardioactivity and historical use as cardiotonic. There are also studies concerning the antibacterial, antioxidant and anti-inflammatory activity of plant extracts. This review summarizes the present knowledge about the biochemical and analytical reserach on Strophantus, in general, and S. sarmentosus, in particular, and describes the current state-of-the-field based on the available sientific literature.

This study presents a systematic review to evaluate the effectiveness of virtual patients in enhancing clinical reasoning skills in medical education, utilizing a hybrid methodology that combines human reviewers and ChatGPT. By analyzing various studies involving conversational virtual patients, the review examines the impact of these digital tools on student learning outcomes and satisfaction. Consistent with previous systematic reviews, our findings suggest that conversational virtual patients can improve clinical competencies, particularly in history-taking and clinical reasoning. Regarding student feedback, satisfaction tends to be higher when virtual patients’ interactions are more realistic, often due to the use of artificial intelligence (AI) and natural language processing (NLP) in the simulators. Furthermore, the study compares the accuracy of AI-driven reviews with human assessments, revealing comparable results. This research highlights AI’s potential to complement human expertise in academic evaluations, contributing to more efficient and consistent systematic reviews in rapidly evolving educational fields.