Intracellular aggregates of the alpha-synuclein protein result in cell loss and dysfunction in Parkinson’s disease and atypical parkinsonism, such as multiple system atrophy and dementia with Lewy bodies. Each of these neurodegenerative conditions, known collectively as alpha-synucleinopathies, may be characterized by a different suite of molecular triggers that initiate pathogenesis. The mechanisms whereby alpha-synuclein aggregates in turn mediate cytotoxicity also remain to be fully elucidated. However, recent studies have implicated the cell-to-cell spread of alpha-synuclein as the major mode of disease propagation between brain regions during disease progression. Here, we review the current evidence for different modes of alpha-synuclein cellular release, movement and uptake, including exocytosis, exosomes, tunnelling nanotubes, glymphatic flow and endocytosis. A more detailed understanding of the major modes by which alpha-synuclein pathology spreads throughout the brain may provide new targets for therapies that halt the progression of disease.

Despite of being an exceptionally biodiversity rich country, the forest coverage of Bangladesh is declining at an alarming rate. Declaration and management of protected areas in this regard is one of the efforts from government side to tackle the loss of biodiversity. The limited numbers of forest-protected areas (FPA), established to conserve the dwindling forest biodiversity of the country with high pressure on them for timber, non-timber forest products, and fuelwood - makes their management challenging. Moreover, most of the FPAs of the country declared only in the recent decades with very limited infrastructure, manpower and policy support for monitoring and governance. Some people-centred approaches for the management of FPAs and alternative livelihood and income generation subsidies although made available through a few project interventions, their number are still inadequate and performance remains less than satisfactory. This chapter provides a critical review of the FPAs of Bangladesh looking at their role in biodiversity conservation, management challenges, and key lessons from previous management interventions with recommendations for the future. It has been revealed that the FPA system of Bangladesh still poorly represents the diverse forest ecosystems with relatively small forest size and lack of corridors for the movement of wildlife. There are ample opportunities to render co-management of FPAs an effective strategy to minimize the conflicts in FPAs management in the country. It is, however, important to ensure the access of local forest-dependent people to different alternative income generating options that may adequately support their livelihoods.

Georgia is ranked fifth highest among states for rates of HIV diagnosis. About 4% of persons living with HIV infection in the United States reside in Georgia, and almost 19% of these people do not know their HIV status. The present study examined the trends and associated factors of HIV testing among adults in Georgia between 2010 and 2014 by analyzing data of the Behavioral Risk Factor Surveillance System (BRFSS). A total of 30,791 persons aged ≥18 years were identified who responded to the question “Have you ever been tested for HIV?” Overall, there were 11,543 respondents who had been tested for HIV, with a decrease in percentage from 49.4% in 2010 to 43.7% in 2014 (p<0.001). Factors associated with HIV testing were being black (p<0.001), being younger than 55 years (p<0.001), single (p=0.02), attaining education level above high school (P<0.001), engaging in HIV high-risk behaviors (p<0.001), and not having healthcare coverage (p=0.03). Overall in Georgia, there has been a decline in the temporal trend of HIV testing, and more than half of adults have never been tested for HIV. For reducing HIV transmission in Georgia, enhancing access and utilization of HIV testing should be a public health priority.

Cranberries are rich in bioactive constituents reported to influence a variety of health benefits, ranging from improved immune function and decreased infections to reduced cardiovascular disease and more recently cancer inhibition. A review of cranberry research targeting cancer revealed positive effects of cranberries or cranberry derived constituents against 17 different cancers utilizing a variety of in vitro techniques; whereas, in vivo studies supported the inhibitory action of cranberries toward cancers of the esophagus, stomach, colon, bladder, prostate, glioblastoma and lymphoma. Mechanisms of cranberry-linked cancer inhibition include cellular death induction via apoptosis, necrosis and autophagy; reduction of cellular proliferation; alterations in reactive oxygen species; and modification of cytokine and signal transduction pathways. Given the emerging positive preclinical effects of cranberries, future clinical directions targeting cancer or premalignancy will be considered

Interrelationships between traditional dental variables are becoming more evident in far reaching aspects of life such as psychosocial interaction, self-esteem, overall health and even occupational performance. This study compares quality of life (QoL) in postmenopausal women (PMW) with poor oral health (POH) with QoL in PMW with good oral health. 200 randomly recruited PMW received a dental evaluation and completed Utian Quality of Life Survey. The participants were divided into POH and healthy groups based on dental exam. Mean scores were calculated for each QoL item, domain and the overall summary score. For each of the four parameters for periodontitis diagnosis, periodontitis patients’ QoL outcomes were compared to those of healthy patients using T-test with threshold of significance at p<0.05. QoL in all fields measured were significantly poorer in the POH compared to the healthy patients, occupational (19.95±5.35vs. 27.56±6.13), health (18.02±8.23 vs. 26.59 ±6.45), emotional (15.68±10.22vs. 21.15±9.15), sexual (6.2±5.98vs. 10.02±5.35), and total score (60.21±25.85 vs. 84.26±22.35). This study finds that PMW with POH, report significantly poorer quality of life. Clinicians caring for PMW should be aware of that oral health impacts QoL and make appropriate referral decisions for patients’ dental care. Keywords: Quality of Life, Oral Health, Post-menopause, Women

Overconsumption of an unbalanced diet and overweight, leading to insulin resistance, dyslipidemia, hepatic steatosis, cardiovascular diseases and obesity, is nowadays a worldwide health issue, with different patterns of metabolic disturbances in the young and adult popula-tions, in both gender. Preclinical models that closely mimic the gradual weight gain that occurs in humans upon consumption of a “western-type” diet (WD) are of great interest. In particular, the diet-induced obesity (DIO) model in the C57BL/6J mouse sub-strain is often used in biomed-ical research, considering that it is prone to metabolic disorders and obesity, and is widely used to generate genetically modified mice. This study aimed to phenotypically characterize the C57BL/6J mouse strain fed a WD-like diet, using high-frequency ultrasound imaging (HFUS) as a complementary tool to longitudinally monitor morphofunctional changes in the liver, heart and kidney associated with DIO. Long term WD feeding increased mice body weight (BW), liver/BW ratio and body condition score (BCS), serum transaminases, glucose and insulin, as well as Homeostasis model assessment (HOMA) indexes, and caused dyslipidemia and insulin resistance. According to the 3Rs, ultrasound imaging has enabled a comprehensive study of metabolic syndrome in mice, in vivo and non-invasive, improving the identification of early stages of diseases.

Hearing loss (HL) is a major clinical, population and public health leading to serious disorders and often early mortality. However, there is a significant paucity in high quality data. Saudi Arabia has a genetically uniform and young population; however factors and estimates on prevalence of HL remains unknown. Background/Objectives: we aimed to determine the frequency, factors, and patterns of HL in different regions. Methods: this study was a descriptive cross-sectional design using a web-based online public questionnaire sent out simultaneously to different regions of Saudi Arabia; namely Eastern, Western, Northen, and Southern as self-administered non-probability sample of social media users mainly WhatsApp, Twitter, and others. Results: Among 789 responses, 6.6 % reported HL, 62.4% were from the Eastern province of which 41.2% were employed and 31.7% were students. Many (36.5%) reported HL &gt; 5-years while 21.2% had programmed and fitted with hearing aids or cochlear implants implying negligence. 19.2% reported diabetes and 51.9% had family history. Ages (11– 50 years) were examined with a slight female predominance (females 59.1%, males 41%). Age was significantly associated with HL (P &lt;0.001) irrespective of gender (males 6.8%, females 6.4%, P value =0.838) reaching peaks at 17.2% in age groups 51-60 years and 25% in 71-80 indicating a risk for HL (OR = 1.43, 95% CI: 0.78-2.81, p = 0.032). Genetic diseases reported as leading cause in 34.6% (OR = 2.23, 95% CI: 1.34-3.58, p = 0.432) followed by noise (26.9%), while other factors including infections, stroke, and fevers made 19.2%. Work involving air or sea travels reported (7.7%) with no significant association (P = 0.628) while history of head injury or trauma (11.5%), or relocation between low- and high-altitudes showed 21.2%. However, frequent noise pollution (OR = 1.54, 95% CI: 0.83-3.01, p = 0.048), regular use of medications (OR = 2.15, 95% CI: 1.03-3.32, p = 0.017), and history of inflammatory disorders (OR = 0.72, 95% CI: 0.32-1.87, p = 0.229) were also associated with higher odds of HL. Conclusion: thus, these findings have significant clinical implications in early diagnosis and management of HL in genetic disorders, diabetes, geriatrics, as well as awareness on family history and occupational health and safety. The study was limited in size and use of online questionnaires. Future large cohort multicenter study would gain more insights.

The objective of this work was to investigate the deacidification of bio-oils (BOs) from triglyceride-based biomass through the application of liquid-liquid extraction (LLE) in a simple stage, using methanol and water as a binary solvent and feed/solvent ratio of 1/1. For this, the effects of process parameters such as the water content present in the solvent, the content of carboxylic acids present in the bio-oil, and the extraction temperature on the deacidification process through the efficiency and distribution coefficient were evaluated, as well as the effects of such parameters on the quality of deacidified bio-oils through physical-chemical analyzes and GC-MS analysis. The results show that such process parameters significantly affect the quality of deacidified bio-oils. The ideal condition to have the highest acid removal, i.e., the highest deacidification efficiency (72.65%), is the one in which the deacidification process is performed with aqueous methanol (5% water) at 35 °C and for BOs that have a total acid number (TAN) equal to 24.38 mg KOH/g. Therefore, the process of deacidification by LLE using aqueous methanol is a promising alternative for removing carboxylic acids and other oxygenated compounds, contributing significantly to the upgrading or improving biofuels produced by catalytic thermal cracking.

In this study, we investigated the features of co-infection with SARS-CoV-2 and nonpathogenic strain LEV8 of coxsackievirus A7 or enterovirus A71 for Vero E6 cells and Syrian hamsters. The investigation of co-infection with SARS-СoV-2 and LEV-8 or EV-A71 in the cell model was shown that a competitive inhibitory effect for these viruses were especially significant against SARS-CoV-2. Pre-infection with enteroviruses in animals caused more than a 100-fold decrease in the levels of SARS-CoV-2 virus replication in the respiratory tracts and more rapid clearance of the lower respiratory tract from infectious SARS-CoV-2. Co-infection with SARS-CoV-2 and LEV-8 or EV-A71 also reduced the severity of clinical manifestations of the SARS-CoV-2 infection for animals. Additionally, the histological data illustrated that co-infection with nonpathogenic coxsackievirus decreased the level of pathological changes by SARS-CoV-2 in the lungs. Research into the chemokine/cytokine profile demonstrated that the studied enteroviruses efficiently triggered this part of antiviral immune response, which can be associated with significant inhibition of SARS-CoV-2 infection. These results demonstrate that there exists a strong viral interference between the studied nonpathogenic strain of coxsackievirus A7 or enteroviruses A71 and SARS-CoV-2 pathogenic for humans in vitro and in vivo.

Background: Thousands of genetic variants have been associated with hematological traits, though target genes remain unknown at most loci. Also, limited analyses have been conducted in African ancestry and Hispanic/Latino populations; hematological trait associated variants more common in these populations have likely been missed. Methods: To derive gene expression prediction models, we used ancestry-stratified datasets from the Multi-Ethnic Study of Atherosclerosis (MESA, including N=229 African American and N=381 Hispanic/Latino participants, monocytes) and the Depression Genes and Networks study (DGN, N = 922 European ancestry participants, whole blood). We then performed a transcriptome-wide association study (TWAS) for platelet count, hemoglobin, hematocrit, and white blood cell count in African (N = 27,955) and Hispanic/Latino (N = 28,324) ancestry participants. Results: Our results revealed 24 suggestive signals (p < 1×10^(-4)) that were conditionally distinct from known GWAS identified variants and successfully replicated these signals in European ancestry subjects from UK Biobank. We found modestly improved correlation of predicted and measured gene expression in an independent African American cohort (the Genetic Epidemiology Network of Arteriopathy (GENOA) study (N=802), lymphoblastoid cell lines) using the larger DGN reference panel; however, some genes were well predicted using MESA but not DGN. Conclusions: These analyses demonstrate the importance of performing TWAS and other genetic analyses across diverse populations and of balancing sample size and ancestry background matching when selecting a TWAS reference panel.

Background: Cutaneous malignant melanoma (CMM) is one of the most aggressive types of skin cancer. Currently, innovative approaches such as target therapies and immunotherapies have been introduced in clinical practice for the treatment of metastatic CMM. Data of clinical trials and real life studies that evaluate the outcomes of these therapeutic associations are necessary to establish their clinical utility. The aim of this study is to investigate the types of oncological treatments employed in the real-life clinical management of patients with advanced CMM in several Italian centers which are part of the Clinical National Melanoma Registry (CNMR), and the oncological outcomes obtained. Methods: CNMR collects data of patients with a histologically confirmed diagnosis of primary CMM treated in one of the 38 Italian institutions (hospitals, research institutes, etc.) participating in the network. Melanoma-specific survival and Overall survival were calculated. Kaplan-Meier curves and medians of OS and 95% CI are presented overall and by immunotherapy and target treatments. The Log-rank test compared curves by treatments. Multivariate Cox regression models were used to estimate the hazard ratios adjusting for confounders and other prognostic factors. Results: The median follow-up time was 36 months (range 1.2-185.1). 787 CMM were included in the analysis with completed information about therapies.Global immunotherapy showed a significant improved survival compared with all other therapies (p=0.001). 75% was the highest reduction of death reached by nivolumab/pembrolizumab immunotherapy (anti-PD1 HR=0.25 95% CI 0.14-0.42), globally immunotherapy was significantly associated with improved survival, either for anti-CTL A4 monotherapy or combined with anti-PD1 (HR=0.47;95% CI 0.33-0.66 and HR=0.26; 95% CI 0.15-0.46, respectively). Conclusions: The nivolumab/pembrolizumab and the combination of ipilimumab can be considered the best therapy to improve survival in a real-world-population. The CNMR can complement clinical registries with the intent of improving cancer management and standardizing cancer treatment.

A truss network was applied to analyze morphometric differentiation among three wild populations of Hoplias microlepis, captured in three different sites from two habitats of Guayas Hydrographic Basin: Daule-Peripa dam, Quevedo and Babahoyo rivers. This study can help to deepen to the knowledge of the species adaptation to different environments and highlights some factors which may be helpful for future management and conservation of the freshwater resources of Ecuador. A sample of 225 adult fish were collected, 49 morphometric characteristics and 6 meristic counts were analyzed, and a statistical model was built through multifactorial discriminant analysis. The standard length of Hoplias microlepis was 32.14 cm, total length 37.82 cm and sexual maturity index 4.39. The Hoplias microlepis with the greatest weight, length and sexual maturity index were in the dam where the food availability is better, and the fishing pressure is lower. Finally, the cluster analysis grouped the fish from the rivers in cluster 1 and those from the dam in cluster 2, being samples of dam clearly distinct from rivers, probably due to differences in the habitat condition. Fish body condition and morphological variation at different sites may be useful indicators for both, habitat disturbance and consequently its conservation, and the sustainability of fishery management plans.

In the era of cloud computing, guaranteeing the safety and effectiveness of data management is of utmost importance. This investigation presents a novel approach that amalgamates sharding concept, encryption, zero-knowledge proofs (zkp), and blockchain technology for secure data retrieval and data access control to improve data security, efficiency in cloud storage and migration. Further we utilize user-specific digital wallets for secure encryption keys in order to encrypt the file before storing into the cloud. As Large files ( greater than 50 MB) or Big data file ( grater than 1 TB) computational complexity is more we leverage on sharding concept to enhance both space and time complexity in cloud storage, hence the large files are divided into shards and stored in different database servers. We also employed blockchain smart contract to enhance secure retrieval of the file and also a secure access method which ensures the privacy of the user. The zk-snark protocol is utilized to ensure the safe transfer of data between different cloud services. By utilizing this approach, data privacy is preserved, as only the proof of the data’s authenticity is shared with the verifier at the destination cloud, rather than the actual data itself. The suggested method tackles important concerns related to data protection, privacy, and efficient resource utilization in cloud computing settings by ensuring it meets all the cloud policies require to store data. As the environment maintains privacy of the user data and by not storing the raw data of the user anywhere, the entire environment is setup as a Zero trust model.

Eotaxin-3 is a key chemokine with a relevant role in eosinophilic esophagitis, a rare chronic immune/antigen-mediated inflammatory disorder. Eotaxin-3 is a potent activator of eosinophil emergence and migration, which may lead to allergic airway inflammation. We investigated by bioinformatics tools the protein structure and the possible effects of the known variations reported in public databases. Following a procedure already established, we created a 3D model of the whole protein and modelled the structure of 105 protein variants due to known point mutations. The effects of the amino acid substitution at the level of impact on protein structure, stability, and possibly function, were detected by the bioinformatics procedure and described in detail. A web application was implemented to browse the results of the analysis and visualize the 3D models, with the opportunity of downloading the models and analyze by the own software. Among 105 amino acid substitutions investigated, the study evidenced in 44 cases at least one change in any of the investigated structural parameters. Other 6 variations are also relevant, although a structural effect is not detected by our analysis, because they substituted amino acids highly conserved, which suggests a possible function role. All these variations should be the object of particular attention, as they may induce loss of functionality in the protein.

In the fast-changing world of software development, the protection of software products has emerged as an imperative requirement. This paper presents a new way to increase the maturity of development teams to reach the highest level of software security. Based on these, the framework uses the Fuzzy Analytic Hierarchy Process (Fuzzy-AHP) to systematically evaluate and enhance the people maturity of software development projects. The essence of the fuzzy logic and AHP technique interaction is to handle the uncertainty and complexity of human factors and team dynamics in the evaluation framework. Using the decision-making model allows the project managers and stakeholders to determine the appropriate areas for improvement and develop the right strategies and actions to nurture a secure and mature development culture. The paper identifies 24 human success factors (HSFs) and human security vulnerabilities (HSVs) and 38 practices for addressing these HSFs and HSVs. Furthermore, we discuss the local and global ranks of each HSF and HSV practice and categorize the identified practices into 9 categories to determine the ranks and weight of each category. Based on collected data, FAHP prioritized these practices; the category “C4: Skill Development and Stakeholder Engagement” is ranked highest at rank-1 and possesses the most significant weight of 0.12435. Similarly, the highest global weight is 0.051506, and the global ranked (rank-1) HSF and HSV practice is “P15: Hands-On Practice and Stakeholder Communication”. Research evidence and case discussions show how the described framework assists in building secure software development (SSD) practices, which can be considered evidence of the application of team maturity to improve cybersecurity in organizations. Additional research directions include improving the framework, especially using highly developed learning techniques and applying the framework to other forms of development.

Abstract: Acute coronary syndrome (ACS) represents the most severe manifestation of coronary artery disease (CAD), characterized by a particularly poor prognosis. Consequently, primary percutaneous coronary intervention (PPCI) is imperative in the event of acute ST-elevation myocardial infarction (STEMI). Interleukin-22 (IL-22) may be a new CAD biomarker because it signals and regulates immune and inflammatory responses. Objectives: To investigate the differences in circulating IL-22 levels between patients with STEMI undergoing PPCI and healthy controls; and to determine if these differences are associated with the culprit coronary artery, door-to-balloon time (DBT), final angiographic result, CAD classification, and the presence of diabetes mellitus (DM). Methods: A total of 280 participants were recruited, comprising 210 STEMI cases and 70 healthy controls. Participants underwent clinical and angiographic evaluation, and serum IL-22 levels were measured using enzyme-linked immunosorbent assay (ELISA). Data analysis was performed using the Mann-Whitney and Fisher’s tests, with a p < 0.05 significant. Results: Serum IL-22 levels were lower in cases (149.63, 84.99–294.56) than in controls (482.67, 344.33–641.00), p < 0.001. Lower IL-22 levels were associated with the right coronary artery (RCA) (144.57, 70.84–242.43; 146.00, 63.60–279.67; 191.71, 121.80–388.97), p = 0.033. IL-22 was lower with shorter DBT (≤ 60 minutes, 106.00, 49.60–171.71; > 60 minutes, 153.00, 88.86–313.60), p = 0.043. Conclusions: IL-22 levels were significantly lower in patients with STEMI compared to healthy controls.

Deforestation through land-use conversion, illegal logging, and timber trafficking is believed to cause ~10% of the annual human carbon dioxide emissions at the global level. Given the large contribution, local and national policies have been set in place in the effort to reduce deforestation and support reforestation. However, accurate assessment of forest carbon stock is expensive and challenging in remote areas and on large geographical scales. To improve carbon stock monitoring and evaluation of fine-scale forest loss, we developed a rapid, automatic, scalable, and cost-efficient generalized deep learning framework that uses diverse remote sensing data and satellite imagery to derive aboveground carbon density from accurate estimates of tree canopy heights at fine-grained resolution (30x30 meters) in remote tropical rainforests. The remote sensing data is composed of Landsat-8, Sentinel-1, land cover, digital elevation model, and NASA CMS airborne LiDAR, as well as vegetation indices, texture metrics, and climatic data. Data sources were compiled into a data pipeline which produced &gt;300 features and 2 million observations over forests in Indonesian Borneo. Using LiDAR swath data on canopy forest high for ~100,000 hectares in Indonesian Borneo to create a training and validation datasets, our neural network model produced aboveground carbon density estimates with R2 of 0.82, which is a significant improvement from comparable works by using Random Forest (R2 of 0.3-0.5). This deep learning framework can be used to facilitate further carbon stock modeling in other forest regions (e.g., Brazil) as well as for the general purpose of climate change mitigation.

Civil construction is one of the oldest known activities in humanity, reports indicate that builders of the Roman Empire already sought the reuse of materials. Currently, considering the depletion of the supply of natural resources, the recycling of solid waste from construction and demolition (CDW), not only provides new products, but also offers ecological and economic alternative. In this context, this research seeks new variables for the disposal of waste from construction and demolition having in the composition of artificial finishing stones an odd possibility to be analyzed. In this research was developed and analyzed a new composite from the construction and demolition waste using as a binder an orthophthalic polyester resin. The residue was sieved and separated by granulometry by the simplex centroid method, the best compacted mixture was determined statically by ANOVA and the Tukey test. The residue was characterized by X-ray fluorescence and the resin by infrared spectroscopy by Fourier transform. Artificial rock plates were produced with 85% residue and 15% resin, by mass, by vibro system, compression and vacuum, later were cut for mechanical, physical and chemical tests. Analysis was performed by scanning electron microscopy of fractured compositions as well as grain sizes. The artificial stone with the best results presented density of 2,256 g/cm3, water absorption of 0.69%, apparent porosity of 1.55%; bending strength of 34.74 MPa and compression of 111.96 MPa; good results in the alterability and thermal tests. In this satisfactory scenario, the use of this waste in the composition of artificial rocks is promising because it directly meets the concept of sustainable development; replacing the concept of end-of-life of the linear economy, by new circular flows of reuse, restoration and renovation, in an integrated process the circular economy; as well as the quality of the final product with properties similar to the artificial rocks already marketed.

The objective of this study was to identify genomic regions and genes associated with resistance to gastrointestinal nematodes in Australian Merino sheep in Uruguay, using the single-step GWAS methodology (ssGWAS), which is based on genomic estimated breeding values (GEBVs) obtained from a combination of pedigree, genomic and phenotypic data. This methodology converts GEBVs into SNP effects. Analysis included 26,638 animals with fecal egg count (FEC) records obtained in two independent parasitic cycles (FEC1 and FEC2), and 1,700 50K SNP genotypes. Comparison of genomic regions was based on genetic variances (gVar(%)) explained by non-overlapping regions of 20 SNPs. For FEC1 and FEC2, 18 and 22 genomic windows exceeded the significance threshold (gVar(%) ≥ 0.22%), respectively. The genomic regions with strong associations with FEC1 were located on chromosomes OAR 2, 6, 11, 21 and 25, and for FEC2 on OAR 5, 6 and 11. The proportion of genetic variance attributed to the top windows was 0.83% and 1.9% for FEC1 and FEC2, respectively. The 33 candidate genes shared between the two traits were subjected to enrichment analysis, revealing a marked enrichment in biological processes related to immune system functions. These results contribute to the understanding of the genetics underlying gastrointestinal parasite resistance and its implications for other productive and welfare traits in animal breeding programs.

The COVID-19 pandemic underscores the significance of vaccine hesitancy in shaping vaccination outcomes. Understanding the factors underpinning COVID-19 vaccination hesitancy is crucial for tailoring effective vaccination strategies. This cross-sectional study, conducted in three communities across the United States and Lebanon, employed surveys to assess respondents' knowledge, attitudes, and perceptions regarding COVID-19 infection and vaccination. Among the 7,196 participants, comprising 6,775 from the US and 422 from Lebanon, vaccine hesitancy rates were comparable at 12.2% and 12.8%, respectively. Notably, a substantial proportion of respondents harbored misconceptions, such as attributing the potential to alter DNA (86.4%) or track individuals (92.8%) to COVID-19 vaccines, and believing in the virus's artificial origins (81%). Primary determinants of hesitancy included perceptions that the vaccine poses greater risk than the infection itself (aOR = 8.7 and 9.4, respectively) and negative recommendations from healthcare providers (aOR = 6.5 and 5.4, respectively). Conversely, positive endorsements from healthcare providers were associated with reduced hesitancy (aOR = 0.02 and 0.4, respectively). Targeting healthcare providers to dispel misinformation and elucidate COVID-19 vaccine risks holds promise for enhancing vaccination uptake.

The aim of this investigation is focused on the effects of hooked-end steel fibers on both fresh and hardened properties of modified self-compacting concretes (SCC). For this purpose, the steel fibers are associated with other residues contents (i.e. marble, granite and rubber). This concatenated materials contents constitutes a novelty since no investigations are reported. It is found that the increase of rubber content, a better ability to absorb energy is observed. This indicates that a good alternative of structural material is provided. Fresh properties are evaluated by using flow, T500 time, V-funnel, J-ring methods. The mechanical behavior is evaluated in terms of compressive strength, tensile strength, static and dynamic modulus of elasticity, and damping ratio. Experimental results of the water absorption, porosity and density are also attained. It is also found that a SCC mixture containing steel fiber, marble/granite residue and rubber content is a potential mixture to be considered when in SCC designing associated with improved damping ratio. Although the rubber content decreases the mechanical behavior and slump flow, the concatenated utilization of MGR and steel fiber contents provide a slight improve in the damping result. An environmental benefit can also be associated since the cement consumption is decreased with marble additions.

Improvement of hydrophysical properties and corrosion resistance of self-compacting concrete to the effects of alternate freezing-thawing and aggressive soils of southern and central Kazakhstan is of interest to a wide range of researchers from the side of practical application of the obtained results in construction practice. It is proposed to form a spatially reinforced fine crystalline structure of cement matrix with maximum dense packing by using a complex modifier (Hyperplasticiser + Polymer + Microsilica + Fibro fibers) in the composition of self-compacting concretes (SCC). The introduction of the calculated amount of the above additives increases the operational reliability of the current SCC compositions, increasing the water resistance to W16, frost resistance to F=500, increasing the compressive strength by 20%, reducing the mass loss of samples during corrosion leaching to 50%. It has been experimentally established that the proposed addition of complex modifier (Hyperplasticiser + Polymer + Microsilica + Fiber fibers) to the SCC composition allows obtaining self-compacting concrete of high quality with improved performance characteristics (compressive strength, water resistance, frost resistance and corrosion resistance). Studies have shown that the complex modifier-modified SCC compositions have a high degree of resistance in aggressive environments and leaching corrosion. Based on the results of the conducted tests, it is possible to recommend the obtained SCC compositions for production of building products working in the zone of alternating freezing-thawing and aggressive soils.

The intricate interplay between driver cognitive dysfunction, mental workload (MWL), and heart rate variability (HRV) provides a captivating avenue for investigation within the domain of transportation safety studies. This article presents a comprehensive review and examines cognitive hindrance stemming from mental workload and heart rate variability. It scrutinizes the mental workload experienced by drivers by leveraging data gleaned from prior studies that employed heart rate monitoring systems and eye tracking technology, thereby illuminating the correlation between cognitive impairment, mental workload, and physiological indicators such as heart rate and ocular movements. The investigation is grounded in the premise that the mental workload of drivers can be assessed through physiological cues, such as heart rate and eye movements. The study discovered that heart rate variability (HRV) and infrared (IR) measurements played a crucial role in evaluating fatigue and workload for skilled drivers. However, the study overlooked potential factors contributing to cognitive impairment in drivers and could benefit from incorporating alternative indicators of cognitive workload for deeper insights. Furthermore, investigated driving simulators demonstrated that an eco-safe driving Human-Machine Interface (HMI) significantly promoted safe driving behaviors without imposing excessive mental and visual workload on drivers. Recommendations were made for future studies to consider additional indicators of cognitive workload, such as subjective assessments or task performance metrics, for a more comprehensive understanding.

The global food production system faces several challenges, including significant environmental impacts due to traditional agricultural practices. The rising demands of consumers for food products that are safe, healthy, and have animal welfare standards have led to an increased interest in alternative proteins and the development of the cellular agriculture field. Within this innovative field, precision fermentation emerges as a promising technological solution to produce proteins with reduced ecological footprints. This review provides a summary of the environmental impacts related to the current global food production, and explore how precision fermentation can contribute to address these issues. Additionally, we will report on the main animal-derived proteins produced by precision fermentation, with a particular focus on those used in the food and nutraceutical industries. The general principles of precision fermentation will be explained, including strain and bioprocess optimization. Examples of efficient recombinant protein production by bacteria and yeasts, such as milk proteins, egg-white proteins, structural and flavoring proteins, will also be addressed, along with case examples of companies producing these recombinant proteins in a commercial scale. Through these examples, we will explore how precision fermentation supports sustainable food production and holds the potential for significant innovations in the sector.

This study delves into the dynamics of 'Variations' and 'Claims' within construction projects, specifically under the FIDIC-Red Book 1999 (FIDIC 1999) framework. It aims to identify, categorize, and devise mitigation strategies for key types of Variations and Claims, aligning with the FIDIC Conditions of Contract. The research, drawing on inputs from construction industry professionals including Contract Administrators and Project Managers, focuses on the MENA re-gion. This choice is driven by the region's extensive adoption of FIDIC standards and its rapidly growing construction sector. Data collection encompassed a questionnaire distributed to 80 industry experts, predominantly through interviews, focusing on countries like Saudi Arabia, UAE, Kuwait, and Egypt. These locations were chosen to reflect diverse construction practices and the involvement of international firms. Utilizing SPSS-V.25 for statistical analysis, the study uncovers the most prevalent and impactful causes of Variations and Claims, highlighting the critical need for managerial intervention. A key feature of this study is the integration of Scientometric Analysis for a quantitative review of current literature, providing a comprehensive academic context. A significant addition to the methodology is the implementation of a k-means clustering analysis. This advanced statistical technique further classifies the data into distinct clusters, each representing unique combinations of 'Frequency' and 'Impact' of Variations and Claims. The k-means analysis elucidates intricate patterns and potential solutions, offering profound insights into effectively managing these issues. These analytical advancements are crucial in identifying significant and manageable responses to reduce the frequency and impact of Variations and Claims in construction projects.

Background: Online survey-based observational cross-sectional study aimed at elucidating experience and attitudes of unstructured population regarding diagnostic imaging. Methods: Invitations to participate were distributed using mixed-mode design to deidentified residents aged 18 years and older. Main outcome measures included morbidity structure and incidence of diagnostic imaging administrations. Results: Respondents (n = 1069) aged 44.3 ± 14.4 years; 32.8% suffered from cardiovascular diseases (CVD); 9.5% had chronic respiratory pathology; 28.9% considered themselves healthy. Respondents with COVID-19 history (49.7%) reported higher rates of computed tomography (CT) (p &lt; .0001), magnetic resonance imaging (MRI) (p &lt; .001), and ultrasound (p &lt; .05). COVID-19 history in CVD respondents shifted imaging administrations towards CT and MRI (p &lt; .05). Every tenth respondent received MRI, CT, and ultrasound on paid basis; 29.0% could not pay for diagnostic procedures; 13.1% reported unavailable MRI. Professional status significantly affected the pattern of diagnostic modalities (p &lt; .05). MRI and CT availability differed between respondents in urban and rural areas (p &lt; .0001). History of technogenic events predisposed responders to overestimate diagnostic value of fluorography (p &lt; .05). Conclusions: Preparedness to future pandemics requires development of community-based outreach programs focusing on people's awareness regarding medical imaging safety and diagnostic value.

The goal was to model the irrigated (IBY) and rainfed (RBY) bean yields, as a function of essential climatic variables (ECVs), in the center (Culiacán) and south (Rosario) from Sinaloa. In Sinaloa, and for the period 1982–2013 (October–March), the following were calculated: a) temperatures. b) average degree days for the bean, c) cumulative potential evapotranspiration and d) cumulative effective precipitation. For ECVs, from the European Space Agency, e) daily soil moisture. f) IBY and RBY, from the Agrifood and Fisheries Information Service. Multiple linear regressions were applied, which modeled IBY–RBY (dependent variables), as a function of ECVs (independent variables). Then, to establish each Pearson correlation (PC) as significantly different from zero, a hypothesis test was applied: PC vs Pearson's critical correlation (CPC). The four models obtained were significantly predictive: IBY–Culiacán (PC = 0.590 > CPC = |0.349|), RBY–Culiacán (PC = 0.734 > CPC = |0.349|), IBY–Rosario (PC = 0.621 > CPC = |0.355|) and RBY–Rosario (PC = 0.532 > CPC = |0.349|). This study is the first in Sinaloa to predict IBY and RBY based on ECVs, contributing to the production of sustainable food.

Background: Orthostatic hypotension (OH) is associated with higher risk of mortality in general population however not studied in cancer population. The study aimed to assess the prevalence of OH in cancer patients compared to the non-cancer population. Methods: A total of 411 patients (mean age 63.5 ± 10.6 years) were recruited: patients with active cancer (n = 223) and patients hospitalized for other reasons but without cancer diagnosis (n = 188). Medical history was collected and an orthostatic challenge test was performed. OH was defined as blood pressure (BP) decrease on standing ≥ 20 mmHg for systolic or ≥ 10 mmHg for diastolic BP in 1 or 3 minutes; or systolic BP decrease &lt; 90 mmHg. Results: The prevalence of OH in cancer was significantly higher than in subjects without cancer- 28.7% vs. 16.5%, respectively, P = 0.003). OH was the most common in lung cancer, 57.5%. In single variable analysis, the predictors of OH were: cancer presence, age ≥ 65 years, and body mass index (BMI) ≥ 30 kg/m2. In the multivariable model, the strongest independent predictor of OH was cancer status doubling the risk of OH; BMI ≥ 30 kg/m2 and diabetes. Conclusions: Cancer patients are characterized by a high prevalence of OH. In this population, the recommendation of routine orthostatic challenge tests should be considered.

The cultivation systems of Coffea spp in a cooperative society in Puebla, Mexico, include rustic, traditional polyculture, commercial polyculture, unshaded monoculture and shaded monoculture. In this work, the properties of the soil were analyzed through physical, chemical, and biological analysis to determine its nutritional status. Composite sample analyses were conducted to determine physical, chemical and microbiological parameters (fungi, actinomycetes, mesophilic bacteria, nitrifying and denitrifying bacteria). Leaf nutrients were determined. Rustic was the cropping system with the highest amount of K (0.76 cmol kg-1) in soil and nutrient assimilation in leaf (N= 2.79%, P= 660.01, K= 17297.22 and Fe= 271.24 mg kg-1) (p= 0.001); in addition to presenting high populations of mesophilic bacteria, fungi and actinomycetes (30.16, 0.59 and 0.83 respectively, x10 6 CFU g-1 soil) and very low nitrification and denitrification rates. The principal component analysis (PCA) (>3.25%) indicated that actinomycetes and K in soil favor the assimilation of Fe, K and P. This Coffea spp cultivation system had a lower impact on soil health than the rest of the systems and favored forest ecosystem conservation.

There is a considerable increase in the use of substances and medical procedures aimed at changing the esthetics of the face, particularly the appearance of the lips. Permanent fillers such as polydimethylsiloxane, also called liquid silicone, are widely used, but their application for facial esthetics is currently obsolete. However, the long-term complications remain a reality, as they can occur decades after the application. Thus, the goal of this case report was to present a complication after 16 years of treatment using liquid silicone. This case report involved a 52-year-old male with a complication of bilateral permanent filler in the upper lip performed 16 years ago, its surgical removal, and histological analysis. Histologically, it was possible to identify a chronic inflammatory, lymphoplasmacytic, and granulomatous reaction, with foreign body giant cells’ reaction, in relation to non-polarizable exogenous material due to the reaction to silicone. The most common complications are granulomas' appearance and material displacement. The case report shows these granulomas are characterized as chronic low-caliber inflammation around the silicone. They have an unknown etiology but are probably multifactorial, from continuous trauma, friction or irritation, iatrogenic factors, infection, immunological mechanisms, and genetic and molecular variations, and can be highly related to the impurity of the injected material.

Hydrogen fuel is gaining particular attention in internal combustion engines. In addition to zero-carbon emissions, major advantages relate to its combustion characteristics, which allow significant increase in thermal efficiency under ultra-lean operation and with very low NOx levels. The ignition system is one of the main technology enablers, as it determines the capability to control ultra-lean operations, avoid backfire phenomena, or reduce the risks of abnormal combustions. The latter results from the hydrogen low ignition energy and it is associated with factors like high-temperature residuals, hot spots, and irregular spark plug discharge. ACIS gen 2-Barrier Discharge Igniter excels in accelerating the initial flame growth speed by the generation of non-equilibrium low-temperature plasma, strong ignition promoter for the combined action of kinetic and thermal effects. Moreover, its volumetric discharge facilitates combustion initiation on a wide region, in contrast to the localized ignition of traditional spark systems. In this work we present for the first time, to the best of our knowledge, experimental results showing the performance of a hydrogen engine with a low-temperature plasma discharge. Tests were conducted on a single-cylinder research engine, achieving ultra-lean conditions with cycle-to-cycle variability results below 2.5%. The analysis indicates that the H2 - BDI combined solution is capable of accelerating the evolution of the flame front compared to traditional spark plugs, leading to a significant reduction in the cycle-to-cycle variability. A meticulous adjustment of the BDI control parameters further enhances igniter performance and contributes to a deeper understanding of the innovative approach proposed in this study.

To assess the impact of a deep learning (DL) denoising reconstruction algorithm applied to identical patient scans acquired with two different voxel dimensions, representing distinct spatial resolutions. This IRB approved prospective study was conducted at a tertiary pediatric center in compliance with the Health Insurance Portability and Accountability Act. We used a General Electric Signa Premier unit (GE Medical Systems, Milwaukee, WI) to acquire two DTI sequences of the left knee on each child at 3T: an in-plane 2.0 x 2.0 mm2 with section thickness of 3.0 mm and a 2 mm3 isovolumetric voxel, neither had an inter-section gap. We used a multi-band DTI acquisi-tion with fat-suppressed single-shot spin-echo echo-planar sequence (20 non-collinear directions; b-values of 0 and 600 sec/mm2). The MR vendor-provided a commercially available DL model applied with 75% noise reduction settings to same subject DTI sequences at different spatial res-olutions. We compared DTI tract metrics from both DL-reconstructed scans and non-denoised scans for femur and tibia, at each spatial resolution. Differences were evaluated using Wilcox-on-signed ranked test and Bland-Altman plots. When comparing DL versus non-denoised diffu-sion metrics in femur and tibia using the 2 mm x 2mm x 3 mm voxel dimension there were no significant differences between tract count (p = 0.1, p =0.14) tract volume (p = 0.14, p = 0.29), or tibial tract length (p=0.16); femur tract length exhibited a significant difference (p

Knowledge of clinical approaches and barriers in managing childhood myopia is limited. This study explores optometrists' knowledge, attitude, and practice towards childhood myopia. A 26-item survey was circulated online among practising optometrists in India. The questionnaire assessed the demographics, knowledge, self-reported clinical practice behaviour, barriers, source of information guiding their management, and extent of adult caregiver engagement for childhood myopia. Of 393 responses, a significant proportion of respondents (32.6%–92.4%) were unaware of the ocular complications associated with high myopia, with less than half (46.5%) routinely measuring axial length in clinical practice. Despite the improved awareness of emerging myopia management options, the uptake remains generally poor, with single-vision distance full correction spectacles (70.3%) being the most common mode of vision correction. Barriers to adopting emerging evidence are medico-legal concerns and the absence of clinical practice guidelines. Original research articles were the primary source of information supporting clinical practice. Most (>70%) respondents considered involving the adult caregiver in their child's clinical decision-making process. While practitioner knowledge, perspective, and practice are improving, childhood myopia management evidence is constantly evolving and remains inconclusive. Evidence-based practice guidelines and continuing education on myopia control might be helpful for practitioners in improving their clinical decision-making skills.

In the present work, the interactions between hydrocortisone and cyclodextrins were investigated. The cyclodextrins selected for this study were hydroxypropyl-α-cyclodextrin, hydroxypropyl-β-cyclodextrin and hydroxypropyl-γ-cyclodextrin. The study was carried out using density measurements, 1H-NMR and FT-IR spectroscopy. Preliminary studies show that hydroxypropyl-α-cyclodextrin has a low affinity for hydrocortisone, while hydroxypropyl-β-cyclodextrin and hydroxypropyl-γ-cyclodextrin have a good affinity for hydrocortisone in both solid state and solution. The study was carried out at two temperatures: 298.15 K and 310.15 K. The results suggest that at both temperatures, the system 2-HP-β-CD + HC induces an increase in the solvent structure, with increasing the solute concentration in the solution, while on the contrary the system 2-HP-γ-CD + HC induces a decrease in the solvent structure when the concentration of the solute in the system increases.

Background: Number of investigations, which are focused on arbuscular mycorrhiza fungi (AMF) biodiversity is still limited. The analysis of AMF taxa in the North Caucasus, a temperate biodiversity hotspot, used to be limited by the genera level. The aim of this study was to define AMF biodiversity at the species level in the North Caucasus biotopes. Methods: Molecular genetic identification of fungi was carried out with ITS1 and ITS2 regions as barcodes, sequencing by Illumina MiSeq, analysis of phylogenetic trees for individual genera, searching the operational taxonomic units (OTUs) with identification at the species level. Sequences from MaarjAM and NCBI GenBank were used as references. Results: We analyzed >10 million reads in soil samples for 3 biotopes to estimate fungal biodiversity. 50 AMF species from 20 genera were found. The valley biotopes (disturbed ecosystems, grasslands) were characterized by a greater AMF diversity, as well as the number of OTUs and species, in comparison with the forest biotopes. Conclusion: Our hypothesis is that high AMF biodiversity for the river valley can be associated with a higher percentage of annual plants in these biotopes, as well as with the active development of restorative successional processes.

We present multi-sensor measurements from satellites, unmanned aerial vehicle, marine radar, thermal profilers and repeated conductivity-temperature-depth casts made in the Kara Gates strait connecting the Barents and the Kara Seas during spring tide in August 2021. Analysis of the field data during an 18-hour period from four stations evidence that a complex sill in the Kara Gates is the site of regular production of intense large-amplitude nonlinear internal waves. Satellite data show a presence of a relatively warm northeastward surface current from the Barents Sea toward the Kara Sea attaining 0.8-0.9 m/s. Triangle-shaped measurements of three thermal profilers revealed pronounced vertical thermocline oscillations up to 40 m associated with propagation of short-period nonlinear internal waves of depression generated by stratified flow passing a system of shallow sills in the strait. The most intense waves were recorded during the ebb tide slackening and reversal when the background flow was predominantly supercritical. Observed internal waves had wavelength of ~100 m and travelled northeastward with phase speeds of 0.8-0.9 m/s. The total internal wave energy per unit crest length for the largest waves was estimated to be equal to 1.0-1.8 MJ/m.

Background: Non-alcoholic fatty liver disease (NAFLD) is manifested by hepatic steatosis, insulin resistance, hepatocyte death, and systemic inflammation. Obesity induces steatosis and chronic inflammation in the liver. However, the precise mechanism underlying hepatic steatosis in the setting of obesity remains unclear. Here we report studies that address this question. Methods: 14 weeks on high-fat diet (HFD) with high sucrose, C57BL/6 mice revealed a phenotype of liver steatosis. Transcriptional profiling analysis of the liver tissues was performed using RNA sequencing (RNA-seq). Results: Our RNA-seq data revealed 692 differentially expressed genes involved in processes of lipid metabolism, oxidative stress, immune responses, and cell proliferation. Notably, the gene encoding neutral sphingomyelinase SMPD3, was predominantly upregulated in the liver tissues of the mice displaying a phenotype of steatosis. Moreover, nSMase2 activity was elevated in these tissues of the liver. Pharmacological and genetic inhibition of nSMase2 prevented intracellular lipid accumulation and TNFα-induced inflammation in in-vitro HepG2-steatosis cellular model. Furthermore, nSMase2 inhibition ameliorates oxidative damage by rescuing PPARα and prevent cell death associated with high glucose/oleic acid-induced fat accumulation in HepG2 cells. Conclusions: Collectively, our findings highlight the prominent role of nSMase2 in hepatic steatosis which could serve as a potential therapeutic target for NAFLD and other hepatic steatosis-linked disorders.

The novel severe acute respiratory coronavirus-2 (SARS-Cov-2) constitutes the causative agent of coronavirus disease-2019 (COVID-19). Several mechanisms have been proposed regarding the development of cardiovascular complications during and after acute COVID-19 infection. COVID-19, caused by SARS-CoV-2, has emerged as one of the deadliest pandemics in modern history. Several clinical and pathophysiologic mechanisms have been proposed for development of cardiovascular complications during and after acute COVID-19 infection. The myocardial injury in patients with COVID-19 has been attributed to coronary spasm, microthrombi formation, plaque rupture, hypoxic injury or cytokine storm disposing the same pathophysiology with the three clinical variants of Kounis syndrome. One of the main proposed mechanisms for development of cardiovascular complications is the angiotensin converting enzyme 2 (ACE2) and its interactions with the renin-aldosterone system (RAAS) and the kinin-kallikrein system (KKS). The ACE2 receptors are expressed throughout the human body located mainly in heart, blood vessels endothelium, lungs, intestines, testes and neurons. The SARS-CoV-2 directly invades the endothelial cells that contain ACE2 receptors and constitutes the main pathway through which the virus enters the endothelial cells. This leads to downregulation of the ACE2 receptors and causes angiotensin II accumulation leading to prothrombotic effects such as hemostatic imbalance via activation of the coagulation cascade, impaired fibrinolysis, thrombin generation, vasoconstriction, endothelial and platelet activation, and pro-inflammatory cytokine release. Indeed, angiotensin I exerts no direct biological function except that its high levels can stimulate catecholamine production. It is metabolized to its biologically active byproduct angiotensin II, a potent vasoconstrictor, by angiotensin converting enzyme (ACE) through cleavage of the two terminal amino acids. SARS-CoV-2 infection prevents the counterbalancing action of the KKS system that normally causes vasodilation and regulates tissue repair, inflammation, cell proliferation, and platelet aggregation. All this cascade leads to the following cardiovascular events: cardiac arrhythmias, cardiac arrest, cardiomyopathy, cytokine storm, heart failure, ischemic myocardial injuries and microvascular disease, Kounis syndrome, long COVID, myocardial fibrosis, myocarditis, new onset hypertension, pericarditis, postural orthostatic tachycardia syndrome (POTS), pulmonary hypertension, stroke, Takotsubo Syndrome, venous thromboembolism and thrombocytopenia. In this narrative review we describe and elucidate when and how the COVID-19 affects the human cardiovascular system, in various areas on the human body that are vulnerable in every category of patients including children and athletes.

Neurodegeneration with brain iron accumulation (NBIA) is a group of rare neurogenetic dis-orders frequently associated with iron accumulation in the basal nuclei of the brain. Among NBIA subtypes, β -propeller protein-associated neurodegeneration (BPAN) is associated with mutations in the autophagy gene WDR45. The aim of this study was to demonstrate autophagic defects and secondary pathological con-sequences in cellular models derived from two patient harboring WDR45 mutations. Both protein and mRNA expression levels of WDR45 were decreased in patient-derived fibro-blasts. In addition, the increase of LC3B upon treatments with autophagy inducers or inhibitors was lower in mutant cells compared to control cells, suggesting decreased autophagosome formation and impaired autophagic flux. Transmission electron microscopy (TEM) analysis showed mitochondrial vacuolization associated with accumulation of lipofuscin-like aggregates containing undegraded material. Autophagy dysregulation was also associated with iron ac-cumulation and lipid peroxidation. In addition, mutant fibroblasts showed altered mitochon-drial bioenergetics. Antioxidants such as pantothenate, vitamin E and α-lipoic prevented lipid peroxidation and iron accumulation. However, antioxidants were not able to correct the ex-pression levels of WDR45 neither the autophagy defect nor cell bioenergetics. Our study demonstrated that WDR45 mutations in BPAN cellular models impaired autophagy, iron metabolism and cell bioenergetics. Antioxidant partially improved cell physiopathology, however autophagy and cell bioenergetics remained affected.

Disease control programs need to identify breeding sites of mosquitoes which transmit malaria and other diseases to target interventions and identify environmental risk factors. Increasing availability of very high resolution drone data provides new opportunities to find and characterize these vector breeding sites. Within this study, we identified land cover types associated with malaria vector breeding sites in West Africa. Drone images from two malaria endemic regions in Burkina Faso and Côte d’Ivoire were assembled and labeled using open-source tools. We developed and applied a workflow using region of interest-based and deep learning methods to classify these habitat types from very high resolution natural color imagery. Analysis methods achieved a dice coefficient ranging between 0.68 and 0.88 for different vector habitat types; however, this classifier consistently identified the presence of specific habitat types of interest. This establishes a framework for developing deep learning approaches to identify vector breeding sites and highlights the need to evaluate how results will be used by control programs.

A refractive lens is one of the simplest, cost-effective and easily available imaging elements. With a spatially incoherent illumination, a refractive lens can faithfully map every object point to an image point in the sensor plane, when the object and image distances satisfy the imaging conditions. However, static imaging is limited to the depth of focus, beyond which the point-to-point mapping can be only obtained by changing either the location of the lens or the imaging sensor. In this study, the depth of focus of a refractive lens in static mode has been expanded using a recently developed computational reconstruction method, Lucy-Richardson-Rosen algorithm (LRRA). The technique consists of three steps. In this first step, the point spread functions (PSFs) were recorded along different depths and stored in the computer as PSF library. In the next step, the object intensity distribution was recorded. The LRRA was then applied to deconvolve the object information from the recorded intensity distributions in the final step. The results of LRRA were compared against two well-known reconstruction methods namely Lucy-Richardson algorithm and non-linear reconstruction.

Fungi critically impact the health and function of global ecosystems and economies. In Canada, fungal researchers often work within silos defined by sub-discipline and institutional type, complicating the collaborations necessary to understand the impacts fungi have on the environment, economy, and plant and animal health. Here, we announce the establishment of the Canadian Fungal Research Network (CanFunNet, https://fungalresearch.ca) whose mission is to strengthen and promote fungal research in Canada by facilitating dialogue among scientists. We summarize the challenges and opportunities for Canadian fungal research that were discussed at CanFunNet’s inaugural meeting in 2019, and identify four priorities for our community: 1) increasing collaboration among scientists; 2) studying diversity in the context of ecological disturbance; 3) preserving culture collections in the absence of sustained funding; and 4) leveraging diverse expertise to attract trainees. We have gathered additional information to support our recommendations, including a survey identifying underrepresentation of fungal-related courses at Canadian universities, a list of Canadian fungaria and culture collections, and a case study of a human fungal pathogen outbreak. We anticipate that these discussions will help prioritize fungal research in Canada, and we welcome all researchers to join this nationwide effort to enhance knowledge dissemination and funding advocacy.

Background: A significant proportion of SARS-CoV-2-infected patients develops respiratory failure. Thromboembolism is also prevalent in coronavirus disease 2019 (Covid-19). Vitamin K plays a role in coagulation and possibly also in lung diseases. We therefore hypothesized that vitamin K is implicated in Covid-19 pathogenesis. Methods: 134 Covid-19 patients and 184 controls were included. Inactive vitamin K-dependent matrix Gla protein (i.e.dp-ucMGP) and prothrombin (i.e. PIVKA-II) were measured, which are inversely related to respectively extrahepatic and hepatic vitamin K status. Desmosine was measured to quantify elastic fiber degradation. Lung involvement and arterial calcifications severity were assessed by computed tomography. Results Dp-ucMGP was elevated in Covid-19 patients compared to controls (P=0.001). Higher dp-ucMGP was found in Covid-19 patients with poor compared to better outcomes (P=0.002). PIVKA-II was normal in 81.8%, mildly elevated in 14.0% and moderately elevated in 4.1% of Covid-19 patients not using vitamin K antagonists. Dp-ucMGP in Covid-19 patients was correlated with desmosine (P<0.001), thoracic aortic calcification (P<0.001) but not with pneumonia severity. Conclusions: Extrahepatic vitamin K status was severely reduced in Covid-19 patients, as reflected by elevated inactive MGP, and related to poor outcome. Procoagulant prothrombin activity remained preserved in the majority of Covid-19 patients, which is compatible with the increased thrombogenicity that is frequently observed in severe Covid-19. Impaired MGP activation was linked to accelerated elastic fiber degradation and premorbid vascular calcifications. A trial should assess whether increasing MGP and protein S activity by vitamin K administration improves Covid-19 outcomes.

A decade after environmental scientists integrated high-throughput sequencing technologies in their toolbox, the genomics-based monitoring of anthropogenic impacts on biodiversity and ecosystems is yet to be implemented by regulatory frameworks. Despite the broadly acknowledged potential of environmental DNA and RNA to cost-efficiently and accurately monitor biodiversity, technical limitations and conceptual issues still stand in the way of its routine application by end-users. In addition, the multiplicity of potential implementation strategies may contribute to a perception of the methodology as being premature or “in development”, hence restraining regulators from binding these tools into legal frameworks. This review focuses on the strengths and limitations of genomics-based strategies that have emerged over the past ten years and have been classified for this purpose into three broad strategies: (A) Taxonomy-based approaches that focus on known bio-indicators or the diversity of taxonomically described taxa, (B) De novo approaches that do not require well-established taxonomy, and (C) Function-based approaches that rely on community-wide metrics, where taxa are interchangeable, or on functional profiles instead of compositional turnovers. We finally propose a roadmap for the implementation of environmental genomics into routine monitoring programs that leverage recent analytical advancements, upon which some critical limitations are alleviated.

Abstract: Hyperuricemia is commonly diagnosed in subjects with abnormal purine metabolism. Prolonged hyperuricemia often associated with gout, which is a vital risk factor for joint dysfunction. The current study was designed to determine the efficacy of vitamin C supplements for treatment of high serum uric acid (UA) among hyperuricemic and gouty patients, and finding-out the effect of supplementation on serum creatinine (Cr) level and glomerular filtration rate (GFR). This intervention study was started in April, 2013, till two months. A convenient sample of 30 adults aged between 24-75 years of both genders was assigned into two study groups: hyperuricemic (n=15) and gouty (n=15) groups. Each participant supplemented with 500 mg/day vitamin C chewable tablets for 2 months. Serum UA, Cr, and GFR were measured before and after treatment. At the end of this study, Cr and GFR enhanced insignificantly in both groups. UA increased insignificantly in gouty group after 2 months by about 0.31 mg/dl. On the other hand, hyperuricemic group showed significant (P ≤0.05) decrease in UA (-0.78 mg/dl) after 2 months duration. In conclusion, supplementation with 500 mg/day vitamin C for 2 months significantly attenuated serum UA for hyperuricemic patients and insignificantly affected serum UA in gouty patients. The uselessness of vitamin C supplements on gouty patients could be associated to a number of possible reasons.

Neurotrophins play a principal role in neuronal survival and differentiation during development, but also in the maintenance of appropriate adult neuronal circuits and phenotypes. In the oculomotor system, we have demonstrated that neurotrophins are key regulators of developing and adult neuronal properties, but with peculiarities depending on each neurotrophin. For instance, the administration of NGF, BDNF or NT-3 protects neonatal extraocular motoneurons from cell death after axotomy, but only NGF and BDNF prevent the downregulation in ChAT. In the adult, in vivo recordings of axotomized extraocular motoneurons have demonstrated that the delivery of NGF, BDNF or NT-3 recovers different components of the firing discharge activity of these cells, with some particularities in the case of NGF. All neurotrophins have also synaptotrophic activity, although to different degrees. Accordingly, neurotrophins can restore the axotomy-induced alterations acting selectively on different properties of the motoneuron. In this review we summarize these evidences and discuss them in the context of other motor systems.

Taxanes have been shown to be the most effective treatment for recurrent or metastatic breast cancer. However, for patients pretreated with taxanes, more active and possibly less toxic drugs are needed. In this retrospective study, we investigated on the effectiveness and safety of eribulin mesylate in 91 taxane-refractory subjects, extracted from the ESEMPIO database, which included 497 metastatic breast cancer patients treated with eribulin allover the Italy. This analysis included only those patients who have shown disease progression while receiving taxane therapy (primary refractory), or those who achieved a response followed by progression while still on therapy (taxane failure). Overall, 41/91 patients (45.2%) showed a clinical benefit; 1 complete response (2.2%) and 16 partial responses (17.6%) were observed. The median progression free survival was 3.1 months (95% CI: 2.8–3.5) and the median overall survival was 11.6 months (95% CI: 8.7–16.7). With regard to toxicity, 53 patients (58%) experienced asthenia/fatigue, 23 (25%) showed peripheral neurotoxicity, 18 (20%) alopecia, 12 (13%) mild constipation and 27 (30%) neutropenia. The toxicity related to the treatment led to eribulin dose reduction in 19 (21%) and discontinuation in 9 (10%) patients, respectively. In conclusion, this study suggests that eribulin is effective and well tolerated also in taxane-refractory patient.

Severe acute respiratory syndrome coronavirus type 2 (SARS-CoV-2) continues to be a global threat due to its ability to evolve and generate new subvariants, leading to new waves of infection. Additionally, other coronaviruses like Middle East respiratory syndrome coronavirus (MERS-CoV, formerly known as hCoV-EMC) which first emerged in 2012, persists and continues to present a threat of severe illness to humans. The continued identification of novel coronaviruses, coupled with the potential for genetic recombination between different strains, raises the possibility of new coronavirus clades of global concern emerging. As a result, there is a pressing need for pan-CoV therapeutic drugs and vaccines. After extensive optimization of an HCV protease inhibitor screening hit, a novel 3CLPro inhibitor (MK-7845) was discovered and subsequently profiled. MK-7845 exhibited nanomolar in vitro potency with broad spectrum activity against a panel of clinical SARS-CoV-2 subvariants and MERS-CoV. Furthermore, when administered orally, MK-7845 demonstrated a notable reduction of viral burdens by &gt;6 log orders in the lungs of transgenic mice infected with SARS-CoV-2 (K18-hACE2 mice) and MERS-CoV (K18-hDDP4 mice).

Several Lung diseases can result in lung damage structural changes, with lung transplantation as a only therapeutic option when the disease reaches an advanced progression, unfortunately, the success of lung transplantation is limited. In this context, lung bioengineering is considered a potential therapeutic alternative and the current approach is based on the use of the natural extracellular matrix (ECM) of the decellularized lung. The use of undifferentiated cells to seed an ECM can be a more practical strategy for lung bioengineering but the sterilization of the organ for this recellularization process is still a challenge. In this sense, Low-Level Laser Therapy (LLLT) can emerge as a potential treatment alternative. Therefore, the objective of this study was to verify if LLLT, can optimize lung recelularization with mesenchymal stem cells by cytokine modulation. For this, we decellularized lungs from C57BL/6 mice perfusing SDS 1% via pulmonary artery, sterilized with LLL (660nm, 100mW, 30s). Whole lung scaffolds were recellularized: (1) Recellularized Lung (2) Recellularized Lung + LLLT. Mesenchymal stem cells derived from human tooth pulp (DPSc) were seeded into lungs and incubated for 24 hours at 37ºC, 5% CO₂, in a bioreactor-like conditions, maintaining CPAP at 20cmH2O, 90% O2, and LLL at wavelength of 808nm, 100mW, 30s. Culture medium were analyzed at 24 hours. H&amp;E, immunostaining, SEM and ELISA assay were performed. We produced viable biological scaffolds absent of DNA content, preserving glycosaminoglycans and collagen I, III and IV, fibronectin, laminin and elastin and lung structure (SEM). The levels of IL-6 and IL-8 were stable during the 24 hours of culture. IFN-γ levels showed significant difference in the DPSc and DPSc+LLLT group in the 24-hour evaluation. The levels of IL-10 decreased after LLLT. These findings highlight LLLT's role in cytokine regulation and contamination prevention during lung recellularization with mesenchymal stem cells. Overall, these results demonstrated that LLLT's modulated cytokine levels and could prevent contamination during the lung recellularization process with mesenchymal stem cells, offering promise for enhanced therapeutic strategies in lung bioengineering.

The overarching vision of Society 5.0 seeks to integrate technology to enhance the quality of life and address social issues, with the primary goal of creating human-centered communities, which nowadays represent the inhabitants of Smart Cities. In this context, this work addresses the design of a modular strategic platform for the smart supervision of public expenditure, to be used by the Directorate of Information, Analysis, and Immediate Reaction (DIARI) of the General Comptroller of the Republic (CGR) of Colombia as a significant contribution towards the country’s transition into the Society 5.0. The design was performed by conducting a detailed literature review on fiscal control; a comprehensive analysis of the legal, organizational, and technological aspects of the country and the CGR; and developing six functional modules focused on topics such as continuous learning, strategic decision-making, distinctive value, strategic achievements, capacity building, and organization, within a three-year implementation plan, through a participatory approach. This plan aims to integrate the platform to enable real-time monitoring, early detection of irregularities, and increased transparency in the management of data and public resources. The strategic platform for the DIARI of the CGR is useful for Smart Cities and the transition into Society 5.0 since it ensures efficient public expenditure management, enhancing transparency and citizen empowerment through modern technologies, data analytics, and active participation in governance processes.

Photovoltaic modules should pass series of tests and examinations, verifying the electrical and thermal characteristics of the module, before being released to the market, examining the properties of the modules should undergo appropriate durability and efficiency tests under real outdoor conditions with exposure to climatic conditions and under laboratory conditions. The performance of photovoltaic cells depends on many factors, such as solar irradiance, module operating temperature, installation location, weather conditions and module shading. In this paper, three selected photovoltaic modules were examined using a large-scale steady-state solar simulator. The current-voltage (I-V) characteristics of the photovoltaic modules were experimentally tested and analyzed. The next step was to implement a three-layer artificial neural network model (MLP). The experimental data obtained in the previous step coupled with output data from MLP were then used in global sensitivity analysis (GSA). Experiments carried out on a large-scale stationary solar simulator showed differences between the values declared by the manufacturer and the values obtained from measurements of PV modules. The first module tested achieved the maximum power point greater than that specified by the manufacturer, while the other two showed power drops; it was 85-87% for the second module, and 95-98% for the third, respectively. The performed global sensitivity analysis (GSA) for the MLP model showed that the parameters: eff (22.9) and Voc/V (14.19) have the largest effect on the power-voltage relationship, while U (7.29) has the smallest effect. The usefulness of machine learning (ML) methods in the comparative analysis of PV modules has been proved.

Exposure to ionizing radiation, accidental or intentional, may lead to delayed effects of acute radiation exposure (DEARE) that manifest as injury to organ systems including kidney, heart, and brain. This study examines the role of activated protein C (APC), a known mitigator of radiation-induced early toxicity, in long-term plasma metabolite and lipid panels that may be associated with DEARE. Male and female cohorts of C57BL/6N wild-type and APCHi transgenic mice were exposed to 9.5 Gy γ-rays with their hind-legs shielded to allow long-term survival that is necessary to monitor DEARE, and plasma was collected at 6 months for LC-MS based metabolomics and lipidomics. We observed significant dyslipidemia, indicative of inflammatory phenotype, upon radiation exposure. Additionally, observance of several other metabolic dysregulations was suggestive of gut damage, perturbations in TCA and urea cycles, and arginine metabolism. We also observed gender and genotype modulated metabolic perturbations post radiation exposure. The APCHi mice showed near normal abundance for several lipids. Moreover, restoration of plasma levels of some metabolites including amino acids, citric acid, and hypoxanthine in APCHi mice are indicative of APC-mediated protection from radiation injuries. With the help of these findings the role of APC in plasma molecular events after acute -radiation exposure in a gender-specific manner can be established for the first time.

There is paucity of data in the available medical literature regarding the parameters of volumetric perfusion of pancreas grafts. Materials and methods From February 5, 2016 to December 23, 2021, we performed perfusion computed tomography in 41 patients at different times after simultaneous pancreas and kidney transplantation. The study group consisted of 18 men (44%) and 23 women (56%) with a long history of type 1 diabetes complicated by terminal chronic renal failure. The results of perfusion computed tomography of the pancreas graft were studied, and the effects of post-transplantation timing and graft revascularization peculiarities on volumetric perfusion parameters were evaluated. Results The median arterial blood flow, arterial blood volume, and permeability of the pancreas graft were 115.1 [99.7;130.3] mL/100 mL/min, 46.7 [37.4;56.9] mL/min and 8.6 [4.1;11.4] mL/100 mL/min, respectively. No statistically significant differences in the averaged perfusion values were found in the head, body, and tail of the pancreas graft. The post-transplantation timing and the number of arteries involved in graft revascularization did not have a significant effect on the volumetric perfusion of the graft. Conclusion The volumetric perfusion results of the pancreas graft correspond to those obtained in the study of pancreatic perfusion in healthy participants.

Background: Cancer therapies predispose survivors to a high symptom burden. This study utilized mobile health (mHealth) technology to assess the feasibility of collecting daily symptoms from adult survivors of childhood cancer and evaluate symptom fluctuation and associations with future health-related quality-of-life (HRQOL). Methods: A prospective study using an mHealth platform to distribute a 20-item cancer-related symptom survey (5 consecutive days each month) and an HRQOL survey (the day after symptom survey) over 3 consecutive months to participants from the Childhood Cancer Survivor Study. PROMIS-29 Profile and Neuro-QOL assessed HRQOL. Daily symptom burden was calculated by summing the severity (mild, moderate, or severe) of 20 symptoms. Univariate linear mixed-effects models analyzed total, person-to-person, day-to-day, and month-to-month variability for the burden of 20 individual symptoms. Multivariable linear regression analyzed the association between daily symptom burden in the first month and HRQOL in the third month, adjusting covariates. Results: Out of the 60 survivors invited, 41 participated in this study (68% enrollment rate); 83% reported their symptoms ≥3 times and 95% reported HRQOL, both in each week across 3 months. Variability of daily symptom burden differed from person-to-person (74%), day-to-day (18%), and month-to-month (8%). Higher first-month symptom burden was associated with poorer HRQOL related to anxiety (regression coefficient: 6.56; 95%CI: 4.10-9.02), depression (6.32; 95%CI: 3.18-9.47), fatigue (7.93; 95%CI: 5.11-10.80), sleep (6.07; 95%CI: 3.43-8.70), pain (5.16; 95%CI: 2.11-8.22), and cognitive function (-6.89; 95%CI: -10.00 to -3.79) in the third month. Conclusion: Daily assessment reveals fluctuations in symptomology, and higher symptom burden was associated with poorer HRQOL in the future. Utilizing mHealth technology for daily symptom assessment improves our understanding of symptom dynamics and sources of variability.

Conclusion: The study highlights the high prevalence of depression among caregivers of geriatric patients in Jeddah and underscores the significant impact of caregiving burden on mental health. These findings emphasize the need for targeted interventions, such as mental health support, respite care programs, and culturally sensitive educational training, to mitigate caregiver burden and enhance the well-being of caregivers.

The binomial nomenclature system, introduced by Carl Linnaeus in the 18th century, has been fundamental for scientific communication and data management. Despite its utility, some scientific names reflect historical biases and ethical issues, including colonial legacies, racism, sexism, and derogatory terms. Recent debates highlight the need to address these injustices, with arguments both for and against revising such names. Critics argue that extensive revisions could disrupt scientific stability, while proponents emphasize the moral imperative to correct these issues. In this opinion paper, we advocate for the establishment of a dedicated committee within international nomenclature bodies to revise taxonomic names with clear ethical concerns and recommend the use of persistent identifiers to effectively manage and track name changes, mitigating potential disruptions to taxonomy and the science that depends on it. By adopting transparent revision processes and making use of digital technology, we can address ethical issues without remarkable upheaval. Science should not perpetuate historical injustices, and it is vital for the scientific community to proactively address social injustices in nomenclature to mitigate ongoing debates and resistance.

Hydrogen is undoubtedly one of the most promising alternatives for generating energy with low environmental impact. However, most hydrogen produced today is derived from fossil fuels, which negatively impacts the environment. In this context, biomass conversion technologies emerge as a sustainable and environmentally friendly alternative to conventional fossil-based processes for hydrogen production. The main objective of this study is to underscore the potential of biomass-derived hydrogen, as one of the key sustainable energy solutions. This work reviews diverse biological and thermochemical pathways for biomass-derived hydrogen production, noting challenges in technology and feedstock diversity. Biomass offers local availability and economic benefits, potentially yielding negative emissions. Biological methods like bio-photolysis and fermentation promise low-energy, waste-recycling solutions despite operational constraints. Thermochemical processes, influenced by biomass type and energy content, favor economies of scale and conventional gasification for economic viability. Hydrothermal gasification shows promise for high-moisture feedstocks. Overall, while thermochemical processes suit centralized large-scale hydrogen production, biological pathways offer decentralized options, necessitating continued innovation for integration into future energy strategies.

Background: This study aimed to evaluate the burden and impact of cardiac and cerebrovascular disease (CCD) on hospital inpatients with type 1 diabetes mellitus (T1DM). Methods: This is a retrospective nationwide cohort study of people with T1DM with or without CCD in the US National Inpatient Sample between 2016 to 2019. The in-hospital mortality rates, length of stay (LoS) and healthcare costs were determined. Results: A total of 59,860 T1DM patients had a primary diagnosis of CCD and 1,382,934 did not. The median LoS was longer for patients with CCD compared to no CCD (4.6 vs. 3 days). Patients with T1DM and CCD had greater in-hospital mortality compared to those without CCD (4.1% vs. 1.1%, p&lt;0.001). The estimated total care cost for all patients with T1DM with CCD was approximately US $326 million. The adjusted odds of mortality compared to patients with non-CCD admission was greatest for intracranial hemorrhage (OR 17.37, 95%CI 12.68-23.79), pulmonary embolism (OR 4.39, 95%CI 2.70-7.13), endocarditis (OR 3.46, 95%CI 1.22-9.84), acute myocardial infarction (OR 2.31, 95%CI 1.92-2.77) and stroke (OR 1.47, 95%CI 1.04-2.09). Conclusions: The burden of CCD in patients with T1DM is substantial and significantly associated with increased hospital mortality and high healthcare expenditures.

This paper investigates the integration of SHM within the frame of Industry 4.0 technologies, highlighting the potential for intelligent infrastructure management through the utilization of Big Data analytics, Machine Learning, and the Internet of Things (IoT). The study also presents a success case focused on a novel SHM methodology for detecting and locating damages in metallic aircraft structures, employing dimensional reduction techniques such as Principal Component Analysis (PCA). By analyzing strain data collected from a network of sensors and comparing it to a baseline pristine condition, the methodology aims to identify subtle changes in local strain distribution indicative of damage. Through extensive Finite Element Analysis (FEA) simulations and a PCA contribution analysis, the research explores the influence of various factors on damage detection, including sensor placement, noise levels, and damage size and type. The findings demonstrate the effectiveness of the proposed methodology in detecting cracks and holes as small as 2mm in length, showcasing the potential for early damage identification and targeted interventions in diverse sectors such as aerospace, civil engineering, and manufacturing. Ultimately, this paper underscores the synergistic relationship between SHM and Industry 4.0, paving the way for a future of intelligent, resilient, and sustainable infrastructure.

Urban tourism has witnessed significant growth in recent years, driven by various factors that foster the transformation of urban areas into tourist hotspots. These factors include a rising interest in culture and heritage, ongoing urban redevelopment and conversion processes, and the introduction of new experiences and activities. Two particularly influential factors contributing to this growth are low-cost travel, which facilitates more accessible access to urban destinations, and the emergence of new types of accommodation, such as short-term rental (also known as local accommodation or Airbnb-type accommodation). This sudden and continuous growth of this type of tourist accommodation brings new challenges to cities and local communities. On the positive side, it contributes to job opportunities, the dynamism of the local economy, and urban revitalization. On the other hand, it also represents more difficulty in retaining the local population in city centers, as more and more buildings are converted into hostels and tourist apartments. In this context, it becomes essential to conduct studies evaluating the impacts of these dynamics in urban areas and how they influence residents' and visitors' perspectives. Therefore, this study aims to identify the main transformations resulting from short-term rental (STR) development, focusing on the impacts felt by tourists and residents in Porto. A questionnaire was distributed to tourists and residents in Porto's city center in June 2023. The results reveal differences in opinions between tourists and residents, particularly concerning historical heritage preservation, local population relocation, and reduced housing availability for residents. Nevertheless, there is a similarity in their opinions regarding the stimulus that local accommodation brings to the economy and the rehabilitation of buildings and urban areas. This study reinforces the need to pay more attention to the future development of tourist accommodation in city centers, especially regarding local policies and territorial planning, to balance better tourism development and local communities' quality of life.

The Mexican Central Pacific (MCP) has discontinuous coral ecosystems with different protection and anthropogenic disturbance. Characterizing the bacterial assemblage associated with the sea urchin Toxopneustes roseus and its relationship with environmental variables will contribute to understanding the species’ physiology and ecology. We collected sea urchins from coral ecosystems at six sites in the MCP during the summer and winter for two consecutive years. The spatial scale represented the most important variation in the T. roseus bacteriome, particularly because of Isla Isabel National Park (PNII). Likewise, spatial differences correlated with habitat structure variables, mainly the sponge and live coral cover. The PNII exhibited a highly diverse bacterial assemblages compared to other sites, characterized by families associated with diseases and environmental stress (Saprospiraceae, Flammeovirgaceae, and Xanthobacteraceae). The remaining five sites presented a constant spatio-temporal pattern, where the predominance of Campylobacteraceae and Helicobacteraceae families were key to T. roseus’ holobiont. However, the dominance of certain bacterial families in the second analyzed year, such as Enterobacteriaceae, suggests that Punto B, and Islas e islotes de Bahía Chamela Sanctuary, were exposed to sewage contamination. Overall, our results improve the understanding of host-associated bacterial assemblage in specific time and space and its relationship with the environmental condition.

To analyse Xuanwei ham flavour quality at different post-ripening times, and to elucidate its microbial diversity, we studied free amino acids and volatile flavouring compounds (VOCs) and their relationships. We determined microbial community changes in Xuanwei ham at 1, 2, 3 and 4 years (W1-4) by high-throughput sequencing, and simultaneously, VOCs and free amino acid contents by gas chromatography-mass spectrometry (GC-MS) and liquid chromatography (LC), respectively. Then heatmap analysis was used to determine correlations between microbial communities, free amino acids and VOCs. A total of 25 free amino acids were detected, among which W3 contained the fewest and most were generally lower than in hams in the other three years. Fifty-nine VOCs were detected, among which were 17 esters, and the highest ester content was found in W4. Atotal of 87508391 reads were obtained from the samples, of which 812844 were clean reads, and the bacterial Chao1 index and Shannon index were significantly higher in W3 than in the other three ham years. In differetly-aged Xuanwei hams, Pseudomonadota was the dominant bacterial phylum, and the most abundant genera were Sarocladium, Klebsiella and Vibrio. Klebsiella was the most abundant genus in W1, and Vibrio in W3, and the second most abundant genera were Sarocladium and Gammaretrovirus. We elucidated differences in Xuanwei ham microflora structures in different years and the main flavor-related microorganisms, thus providing a theoretical basis for subsequent Xuanwei ham storage, quality and improvement.

Epidemiological studies point cholesterol as a possible key factor for both prostate cancer incidence and progression. So, it could represent a targetable metabolite as the most aggressive tumors also appear to be sensitive to therapies designed to decrease hypercholesterolemia, such as statins. However, whether and how cholesterol, through its dietary uptake and its metabolism, could be important for early tumorigenesis, remains unknown. Oncogene clonal induction in Drosophila melanogaster accessory gland allows to reproduce tumorigenesis from initiation to early progression, where tumour cells undergo basal extrusion to form extra-epithelial tumors. Here we show that these tumors accumulate lipids, and especially esterified cholesterol, as in human late carcinogenesis. Interestingly, high cholesterol diet displays limited effect on accessory gland tumorigenesis. On the contrary, cell-specific downregulation of cholesterol uptake, intracellular transport or metabolic response, impairs the formation of such tumors. Furthermore, in this context, high cholesterol diet suppresses this impairment. Taken together, these results reveal that during early tumorigenesis, tumour cells strongly increase their uptake and use of dietary cholesterol to specifically promote the step of basal extrusion. Interestingly, expression data from primary prostate cancer tissues indicate an early signature of redirection from cholesterol de novo synthesis to uptake. Altogether, these results suggest by which mechanism reduction of dietary cholesterol could lower the risk and slow down the progression of prostate cancer.

In this paper we explore the known connection among sustainability, resilience, and well-being within the framework of active inference. Initially, we revisit how the notions of well-being and resilience intersect within active inference before defining sustainability. We adopt a holistic concept of sustainability denoting the enduring capacity to meet needs over time without depleting crucial resources. It extends beyond material wealth to encompass community networks, labor, and knowledge. Using the Free Energy Principle, we can emphasize the role of fostering resource renewal, harmonious system-entity exchanges, and practices that encourage self-organization and resilience as pathways to achieving sustainability, both in an agent and in collectives. We start by connecting Active Inference with well-being, building on exsiting work. We then attempt to link resilience with sustainability, asserting that resilience alone is insufficient for sustainable outcomes. While crucial for absorbing shocks and stresses, resilience must be intrinsically linked with sustainability to ensure that adaptive capacities do not merely perpetuate existing vulnerabilities. Rather, it should facilitate transformative processes that address the root causes of unsustainability. Sustainability, therefore, must manifest across extended timescales and all system strata, from individual components to the broader system, to uphold ecological integrity, economic stability, and social well-being. We explain how sustainability manifests at the level of an agent, and then at the level of collectives and systems. To model and quantify the interdependencies between resources and their impact on overall system sustainability, we introduce the application of network theory and dynamical systems theory. We emphasize the optimization of precision or learning rates through the active inference framework, advocating for an approach that fosters the elastic and plastic resilience necessary for long-term sustainability and abundance.

Modified mRNAs (modRNAs) are an emerging delivery method for gene therapy. In particular, the modRNA-based COVID-19 vaccines have proven that modRNA is a safe and effective therapeutic tool. Moreover, modRNA has the potential to treat various human diseases including cardiac dysfunction. Acute myocardial infarction (MI) is a major cardiac disorder that currently lacks curative treatment options. MI is commonly accompanied by fibrosis and impaired cardiac function. Our group previously demonstrated that the matricellular protein CCN5 inhibits cardiac fibrosis (CF) and improves cardiac dysfunction. However, it remains elusive whether the early intervention of CF under stress conditions is beneficial or more detrimental due to potential adverse effects such as left ventricular (LV) rupture. To obtain acute CCN5 expression, we used modRNA-mediated gene transfer in a mouse MI model. To evaluate CCN5 activity, we established two independent experimental schemes: 1) preventive intervention and 2) therapeutic intervention. Cardiac function and structural changes were measured by echocardiography and magnetic resonance imaging. Finally, fibrosis and the underlying molecular pathway were analyzed by western blotting, quantitative real-time polymerase chain reaction, and immunohistochemistry. The modRNA-CCN5 gene transfer successfully ameliorated CF and enhanced cardiac function in both preventive and therapeutic interventions without LV rupture or any adverse cardiac remodeling. Conclusively, early intervention in CF by modRNA-CCN5 gene transfer is an efficient and safe therapeutic modality for treating MI-induced heart failure without adverse structural remodeling.

Abstract: (1) Background: After the COVID-19 pandemic, there is increasing concern regarding the immunity of population to SARS-CoV-2 variants, particularly the Omi-cron variant and its sub-lineages. (2) Methods: The study involved analyzing the im-mune response and symptomatology of 27 vaccinated individuals who were subse-quently infected by Omicron sub-lineages. Blood samples were collected for serological analysis, including the detection of IgG antibodies reactive to the Nucleocapsid (N) and Spike (S) antigens of SARS-CoV-2. Additionally, participants were interviewed to assess the intensity of symptoms during the infection. (3) Results: Despite the high levels of anti-Spike IgG observed after vaccination, all participants were infected by Omicron sub-lineages. The most common symptoms reported by participants were fever or chills, sore throat, and cough. Surprisingly, the levels of anti-Spike IgG found prior to infection did not correlate with symptom severity post-infection. However, it was observed that high post-infection anti-Nucleocapsid IgG levels correlates with mild symptoms during the course of the disease, suggesting a potential role for anti-N antibodies in disease resolution. (4) Conclusions: The high levels of IgG anti-Spike resulting from vaccination may not provide complete protection against infection by the Omicron variant. Addi-tionally, our data suggest that anti-Nucleocapsid IgG titers are negatively correlated with the intensity of the symptoms during mild infections. These findings underscore the importance of ongoing surveillance of viral variants and continuous adaptation of vaccination strategies to ensure efficacy against SARS-CoV-2 variants.

Accurate diagnosis for the 400 million people with rare diseases is critical for healthcare decisions, prognosis, understanding disease mechanisms, and identification of treatments. Despite advances in genome sequencing, barriers such as high interpretation costs, diagnostic expertise, throughput associated delays, and uncertain variant classifications persist, with demand exceeding capacity. Many variant classification methods focus narrowly on specific consequences, leading to the use of complex integrative pipelines that often overlook transcript variability and lack prediction transparency. To overcome these limitations, we introduce DITTO. This transparent, transcript-aware machine-learning method demonstrates superior overall performance in accuracy, recall, and precision when compared to existing tools. DITTO is publicly available at https://github.com/uab-cgds-worthey/DITTO

To get more data concerning the influence of fertilizers (organic and mineral) on different forage plants existing in North-eastern Romanian grassland, the mass fractions of 14 essential, enzymatic, or considerd toxic elements was determined by Instrumental Neutron Activation Analysis together with the amount of crude proteins, ash, fibres as well as ether fact extract. Final results showed a significant variance of the content of analysed elements on organic as well as on mineral fertilized experimental plots, i.e. the content increased in 24% of plots, decreased in 23%, and remained unchanged in 45% while in 8% of plots their content was below the detection limits, as the case of Se. At the same time, an increase content of crude protein and ether extract was evidenced in fertilized grasses for all applied fertilizers while other global indicators such as neutral and acid fibre of sufuric lignin content decreased, suggesting significant higher nutritional values of fertilized forage plant.

In the dynamic interplay between people and their physical environments, the Global South stands as a mosaic undergoing a multitude of transformative influences in architecture and urbanism where examining social sustainability becomes imperative. While prevailing attention remains on environmental and economic sustainability, this study addresses a persistent gap in the urban literature by focusing on the dynamic and manifold nature of social sustainability. Positioning itself within the context of sustainable development, the study links the pursuit of social aspects of sustainability with selected unique urban contexts from the Global South. Five cases that include Alexandria (Egypt), Tripoli (Libya), Basra (Iraq), Lilongwe (Malawi), and Accra (Ghana) are discussed through multi-layered investigations that involve attitude surveys, interviews, focus groups, participatory systematic observations, and behavioral mapping, engaging directly with inhabitants and stakeholders. Uncovering people-place narratives in the identified contexts, the cases are developed into five knowledge typologies that serve as practical tools for planning and design decision-making, policy formulation, and academic discourse. Discussions are conceived to demonstrate the transformative role people-place narratives play in fostering a more sustainable and equitable urban future. Conclusions are drawn to offer practical insights for stakeholders involved in various capacities in shaping the urban landscape of the Global South.

Over the last decades, an important number of regional and global Digital Elevation Models (DEMs) have been released publicly. As a consequence, researchers need to choose between several of these models to perform their studies and to use these DEMs as third-party data to compute derived products (e.g., for orthorectification). However, the comparison of DEMs is not trivial. For most quantitative comparisons, DEMs require to be expressed in the same Coordinate Reference System (CRS), sampled over the same grid (i.e., be at the same ground sampling distance with the same pixel-is-area or pixel-is-point convention), and with heights relative to the same Vertical Reference System (VRS). Thankfully, many open tools allow us to perform these transformations precisely and easily. Despite these rigorous transformations, local or global planimetric displacements may still be observed from one DEM to another. These displacements, or disparities, may lead to significant biases in comparisons of DEM elevations or derived products such as slope, aspect or curvature. Therefore, the control of DEM planimetric accuracy is certainly the most important task to perform at first before any comparison. This paper presents the disparity analysis method enhanced to achieve a sub-pixel accuracy, by interpolating the linear regression coefficients computed within an exploration window. This new method is significantly faster than oversampling the input data because it uses the correlation coefficients that have been already computed in the disparity analysis. To demonstrate the robustness of this algorithm, artificial displacements have been performed in a 11x11 grid with a 0.1-pixel step in both directions. The Copernicus DEM GLO-30 has been interpolated by a “classical” bicubic to achieve these 11x11 displacements. This validation method has been applied in four 10 km x 10 km DEMIX tiles showing different height distributions. Globally, this new sub-pixel accuracy method is robust. Artificial displacements have been retrieved with with typical errors (e_b) ranging from 12 to 20 % of the pixel size (worst case in Croatia).These errors in displacement retrievals are not constant in the 11x11 grid and the overall error E_b depends on the roughness (altimetry variations) encountered in the different tiles. The second idea of this paper is to assess the impact of the bicubic parameter (slope of the weight function at a distance d=1 of the interpolated point) on the accuracy of the displacement retrieval. By considering E_b as a quality indicator, tests have been performed in the four DEMIX tiles making the bicubic parameter vary between -1.5 and 0.0 by step of 0.1. For each DEMIX tile, the best bicubic (BBC) parameter b* is interpolated from the four E_b minimal values. This BBC parameter b* is low for flat areas (around -0.95) and higher in mountainous areas (around -0.75). The roughness indicator is the standard deviation of the slope norms computed from all the pixels of a tile. A logarithmic regression analysis performed between the roughness indicator and the BBC parameter b* computed in 67 DEMIX tiles shows a high correlation (r=0.717). The logarithmic regression formula estimating the BBC parameter from the roughness indicator is generic and may be applied to estimate the displacements between two different DEMs. This formula may also be used to set up a future Adaptative Best BiCubic (ABBC) that will estimate the local roughness in a sliding window to compute a local BBC.

This paper provides a comparative analysis of AES (Advanced Encryption Standard) and Salsa20 algorithm implementations, focusing on power consumption efficiency in passive RFID (Radio Frequency Identification) tags and ultra-low-power devices. The main objective of this work is to determine which of these algorithms is more suitable to operate in these types of devices. For this purpose, ASIC (Application-Specific Integrated Circuit) implementations of AES and Salsa20 based on low-power approaches were developed and their power consumption was evaluated. Results demonstrate that Salsa20 power consumption is lower than AES (2.82μW and 4.01μW, respectively - both in 0.18μm), indicating that Salsa20 is a better choice than AES for passive RFID tags.

Obesity is one of the most prevalent chronic diseases and has become a global epidemic. Obesity leads to a greater risk of breast cancer (BC), metastases, recurrence, and decreased survival. For sustained weight loss, bariatric surgery is effective as a long-term solution. Bariatric surgery is associated with improved outcomes of several cancers including BC, although the mechanisms mediating this protection are unknown. We hypothesized that elevated bile acid pools detected after bariatric surgery may be factors that contribute to improved BC outcomes. Indeed, patients with greater expression of the bile acid receptor FXR displayed improved survival in specific BC subtypes. Patients with tumors that are estrogen receptor negative (ER-) displayed significantly elevated survival with higher FXR (NR1H4) expression compared to lower expression. FXR is a nuclear hormone receptor activated by bile acids. Therefore, we posited that activating FXR using an established FDA-approved agonist would display anticancer effects. Indeed, FXR agonism by the bile acid mimetic known commercially as OCALIVA (“OCA”), or Obeticholic acid (INT-747), significantly reduced BC progression and overall tumor burden in a pre-clinical model. In human and murine BC analyses in vitro, agonism of FXR significantly and dose-dependently inhibited proliferation, migration, and viability. In contrast, synthetic agonism of another common bile acid receptor, the G protein-coupled bile acid receptor (GPBAR1, TGR5) which is mainly activated by secondary bile acids, failed to significantly alter cancer cell dynamics. In conclusion, agonism of FXR by primary bile acid memetic OCA yields potent anti-tumor effects potentially through inhibition of proliferation and migration and reduced cell viability. Findings suggest that FXR is a tumor suppressor gene with high potential for personalized therapeutic strategies for individuals with BC.

Vitamin D status may impact acute affective symptomatology and the severity of symptoms in patients with bipolar disorder (BD). Therefore, this cross-sectional study analyzed 25(OH)D, 24,25(OH)2D, and the vitamin D metabolite ratio (VMR) in BD and correlated the results with clinical affective symptomatology and functionality. The inactive precursor 25(OH)D and its principal catabolite 24,25(OH)2D were measured simultaneously with a validated liquid chromatography tandem mass-spectrometry method in 170 BD outpatients and 138 healthy controls. VMR was calculated as follows: VMR=100*(24,25(OH)2D/25(OH)D). The psychometric assessment enclosed: Beck Depression Inventory-II, Hamilton Depression Rating Scale, Young Mania Rating Scale, Global Assessment of Functioning, and number of suicide attempts. We did not find a significant difference between patients and controls in the concentrations of 25(OH)D and 24,25(OH)2D. Additionally, the VMR was comparable in both groups. The calculations for the clinical parameters showed a negative correlation between the Young Mania Rating Scale and 24,25(OH)2D (r = -.154, p = .040). Based on the small effect size and the predominantly euthymic sample, further exploitation in individuals with manic symptoms would be needed to confirm this association. In addition, long-term clinical markers, and an assessment in different phases of the disease may provide available additional insights.

In view of the increasing age of cardiac surgery patients, questions arise about the expected postoperative quality of life and the hoped-for prolonged life expectancy. Little is known so far about this weighting by the patients concerned. This study aims to obtain information on the patient’s preferences. Between 2015 and 2017, data from 1349 consecutive patients from seven heart centers in Germany undergoing cardiac surgery were analyzed. Baseline data regarding the patient’s situation as well as a questionnaire regrading quality of life versus lifespan were taken preoperatively. Patients were divided by age into 4 groups: below 60, 60-70, 70-80, and above 80 years. As a result, if one had to decide between quality of life and length of life, about 60% of the male patients decided for quality of life, independent of their age. On the other hand, female patient’s decision for quality of life increased significantly with age, from 51% in the group below sixty to 76% in the group above eighty years. This finding suggests that the female patients adapt their preferences with age whereas male patients do not. This should impact further treatment decisions of elderly patients in cardiac surgery within a shared decision-making process.

F-type ATP synthases play a key role in oxidative and photophosphorylation processes producing adenosine triphosphate (ATP) for most biochemical reactions in living organisms. In contrast to the mitochondrial FOF1-ATP synthases those of chloroplasts are known to be mostly monomers with approx. 15% fraction of oligomers interacting presumably non-specifically in a thylakoid membrane. To shed light to the nature of this difference we studied interactions of the chloroplast ATP synthases using small-angle X-ray scattering (SAXS) method. Here, we report evidence of I-shaped dimerization of solubilized FOF1-ATP synthases from spinach chloroplasts at different salinity. The structural data were obtained by SAXS and showed dimerization in response to changes in ionic strength. The best model describing SAXS data was two ATP-synthases connected through F1/F1’ parts, presumably via their δ-subunits, forming dimers with the “I” shape. Such I-shaped dimers might possibly connect the neighboring lamellae in thylakoid stacks assuming that the FOF1 monomers comprising such dimers are embedded in different thylakoid membranes. If this type of dimerization exists in nature, it might be one of the pathways of inhibition of chloroplast FOF1-ATP synthase for preventing of ATP hydrolysis in dark, when salinity in plant chloroplasts is rising. Together with a redox switch inserted into a γ-subunit of chloroplast FOF1 and lateral oligomerization, an I-shaped dimerization might comprise a subtle regulatory process of ATP synthesis and stabilize the structure of thylakoid stacks in chloroplasts.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has affected millions of people worldwide since its emergence in 2019. The current global pandemic was driven by human-to-human transmission. Knowing the zoonotic origin of the disease and the potential capacity of the virus to adapt to other species, it is important to understand the extent of natural SARS-CoV-2 infection of animals, in particular cats and dogs in households that are in direct contact with their owners. Hong Kong and Seoul are two of the most densely-populated urban cities in Asia, where companion animals often live in close contact with humans. In this study, we screened sera from 1,040 cats and 855 dogs during the early phase of the pandemic in Hong Kong and Seoul for SARS-CoV-2 antibodies by using an ELISA that detects antibodies against the receptor binding domain (RBD) of the viral spike protein. Sera testing positive on ELISA were also tested for the presence of neutralizing antibodies using a surrogate virus neutralization (sVNT) and plaque reduction neutralization test (PRNT). Among feline sera, 4.51% and 2.54% of samples from Korea and Hong Kong, respectively, tested ELISA positive. However only 1.64% of samples from Korea and 0.18% from Hong Kong tested positive by sVNT, while only 0.41% of samples from Korea tested positive by PRNT. Among canine samples, 4.94% and 6.46% from Korea and Hong Kong, respectively, tested positive by ELISA, while only 0.29% sera from Korea were positive on sVNT and no canine sera tested positive by PRNT. These results confirm a low seroprevalence of SARS-CoV-2 exposure in companion animals in Korea and Hong Kong. The discordance between RBD-ELISA and neutralization tests may indicate possible ELISA cross-reactivity with other coronaviruses, especially in canine sera.

Bladder cancer (BC) is the most common neoplasm of the urinary tract, which originates in the epithelium that covers the inner surface of the bladder. The molecular BC profile has led to the development of different classifications of non-muscle invasive bladder cancer (NMIBC) and muscle-invasive (MIBC). However, the genomic BC landscape profile of the Mexican population, including NMIBC and MIBC, is unknown. In this study, we aimed to identify somatic single nucleotide variants (SNVs) and copy number variations (CNVs) in Mexican patients with BC and their associations with clinical and pathological characteristics. We retrospectively evaluated 37 patients treated between 2012 and 2021 at the National Cancer Institute - Mexico (INCan). DNA samples were obtained from paraffin-embedded tumor tissues and ran exome sequencing. Strelka2 and Lancet packages were used to identify SNVs and insertions or deletions. FACETS was used to determine CNVs. We found a high frequency of mutations in TP53 and KMT2D, gains in 11q15.5 and 19p13.11-q12, and losses in 7q11.23. STAG2 mutations and 1q11.23 deletions were also associated with NMIBC and low histologic grade.

COVID-19 vaccination certificates (CVCs) have played a key role in safe reopening of borders for international travel and trade, so understanding key stakeholder perceptions of enablers and barriers for their effective use is critical. The COVID-19 Vaccination Policy Research and Deci-sion-Support Initiative in Asia (CORESIA) was established to address policy questions related to CVCs. We conducted two online surveys, i.e., one for the public and one for health and non-health sector experts, from June to October 2021 in nine Asian countries. Descriptive analysis identified participants, enablers, and barriers. Most participants (78% public, 89% experts) accepted the use of CVCs, primarily to resume international travel (76%). Most respondents in both surveys wanted the minimum vaccination coverage to be 60% before CVCs were implemented nation-wide. Most of the public (82%) agreed to maintain existing non-pharmaceutical interventions, while most experts wanted risk-based testing and quarantine policy for incoming travellers (51%) and both digital and paper format CVCs (64%). Support for CVCs for international travel remains high in Asia. Recognising key enablers and barriers for effective use of CVCs from COVID-19 pandemic may help policymakers draft effective border policies for future epidemics.

In recent years, metabolomics has been used as a powerful tool to better understand the physiology of neurodegenerative diseases and identify potential biomarkers for progression. We used targeted and untargeted aqueous, and lipidomic profiles of the metabolome from human cerebrospinal fluid to build multivariate predictive models distinguishing patients with Alzheimer’s disease (AD), Parkinson’s disease (PD), and healthy age-matched controls. We emphasize several statistical challenges associated with metabolomic studies where the number of measured metabolites far exceeds sample size. We found strong separation in the metabolome between PD and controls, as well as between PD and AD, with weaker separation between AD and controls. Consistent with existing literature, we found alanine, kynurenine, tryptophan, and serine to be associated with PD classification against controls, while alanine, creatine, and long chain ceramides were associated with AD classification against controls. We conducted a univariate pathway analysis of untargeted and targeted metabolite profiles and find that vitamin E and urea cycle metabolism pathways are associated with PD, while the aspartate/asparagine and c21-steroid hormone biosynthesis pathways are associated with AD. We also found that the amount of metabolite missingness varied by phenotype, highlighting the importance of examining missing data in future metabolomic studies.

Background: Clean cookstove interventions can theoretically reduce exposure to household air pollution and benefit health, but this requires near-exclusive use of the stoves, with simultaneous disuse of traditional stoves. Previous cookstove trials have reported low adoption of new stoves and/or extensive continued traditional stove use. Methods: The Household Air Pollution Intervention Network (HAPIN) trial randomized 3195 pregnant women in Guatemala, India, Peru, and Rwanda either to a liquefied petroleum gas (LPG) stove and fuel intervention (n = 1590) or to control (n = 1605). The intervention consisted of an LPG stove and two initial cylinders of LPG, free fuel refills delivered to the home, and regular behavioral messaging. We assessed intervention fidelity (delivery of the intervention as intended) and adherence (intervention use) through the end of gestation, as relevant to the first primary health outcome of the trial: infant birth weight. Fidelity and adherence were evaluated using stove and fuel delivery records, questionnaires, visual observations, and temperature-logging stove use monitors (SUMs). Results: 1585 women received the intervention, at a median (interquartile range) of 8.0 (5.0–15.0) days post-randomization and gestational age of 17.9 (15.4–20.6) weeks. Over 96% reported cooking exclusively with LPG at two follow-up visits during pregnancy. Less than 4% reported ever running out of LPG. Complete abandonment of traditional stove cooking was observed in over 67% of intervention households. 31.4% removed their traditional stoves upon receipt of the intervention, and among those who retained traditional stoves, the majority did not use them: traditional stove use was detected via SUMs on a median (interquartile range) of 0.0% (0.0%, 1.6%) of follow-up days (median follow-up = 134 days). Conclusions: Fidelity of the HAPIN intervention, as measured by stove installation, timely ongoing fuel deliveries, and behavioral reinforcement as needed, was high. Exclusive use of the intervention during pregnancy was also high.

Physical processes play important roles in controlling eutrophication and oligotrophication. In stratified lakes, internal waves can cause vertical transport of heat and nutrients without breaking the stratification, through boundary mixing events. Such is the case in tropical Valle de Bravo (VB) lake, where strong diurnal winds drive internal waves, boundary mixing and hypolimnetic warming during stratification periods. We monitored VB during 18 years (2001-2018) when important water-level fluctuations (WLF) occurred, affecting mixing and nutrient flux. Mean hypolimnetic temperature increase (0.06–1.04°C month-1) occurred in all the stratifications monitored. We analyzed temperature distributions and modeled the hypolimnion heat budget to assess vertical mixing between layers (26,618–140,526 m-3h-1), vertical diffusivity coefficient KZ (6.2x10-7–3.3x10-6 m2s-1) and vertical nutrient entrainment to epilimnion on monthly scale. Stability also varied as a function of WLF. Nutrient flux to the epilimnion ranged 0.36–5.99 mg m-2d-1 for soluble reactive phosphorus (SRP) and 5.8–97.1 mg m-2d-1 for dissolved inorganic nitrogen (DIN). During low water-level years, vertical nutrient fluxes increase and can account for up to &gt;40% of the total external nutrients load to the lake. Vertical mixing changes related to WLF affect nutrient recycling, their flux to sediments, ecosystemic metabolic balance and planktonic composition of VB.

In 2008, Ecuador recognized the Constitutional Rights of Nature in a global first. This recognition implies a major shift in the human-nature relationship, from one between a subject with agency (humans) and an exploitable object (Nature), to a more equilibrated relationship of respect. However, the lack of a standard legal framework has left room for subjective interpretations and variable implementation. The recent widespread concessioning of pristine ecosystems to mining industries in Ecuador has set up an unprecedented conflict and test of these rights. Currently, a landmark case involving Los Cedros Protected Forest and mining companies has reached the Constitutional Court of Ecuador. If Ecuador’s highest Court rules in favor of Los Cedros and the Rights of Nature, it would set a legal precedent with enormous impact on biological conservation in Ecuador and, potentially, the world. Such a policy shift offers a novel conservation strategy, through citizen oversight and action.

Background: Real-world data on the molecular epidemiology of EGFR resistance mutations at or after progression with first- or second-generation EGFR-TKIs in patients with advanced NSCLC are lacking. Methods: This ongoing observational study was carried out by 23 hospital-based physicians in Greece. The decision to perform Cobas® EGFR Mutation Test v2 in tissue and/or plasma at disease progression was made before enrollment. For patients with negative/inconclusive T790M plasma-based results, tissue re-biopsy could be performed. Results: Ninety-six (96) eligible patients were consecutively enrolled (median age: 67.8 years) between July-2017 and September-2019. Of the patients, 98% were tested upon progression using plasma and 2% using tissue/cytology biopsy. The T790M mutation was detected in 16.0% of liquid biopsies. Tissue re-biopsy was performed in 22.8% of patients with a T790M-negative plasma result. In total, the T790M positivity rate was 21.9%, not differing between patients on first- or second-generation EGFR-TKI. Higher (≥2) ECOG performance status and longer (≥10 months) time to disease progression following EGFR-TKI treatment initiation were associated with T790M positivity. Conclusions: Results from plasma/tissue-cytology samples in a real-world setting, yielded a T790M positivity rate lower than previous reports. Fewer than one in four patients with negative plasma-based testing underwent tissue re-biopsy, indicating the challenges in routine care settings.

The night has historically been neglected in both disciplinary and interdisciplinary research. To some extent, this is not surprising, given the diurnal bias of human researchers, and the difficulty of performing work at night. The night is, however, a critical element of biological, chemical, physical, and social systems on Earth. Moreover, research into social issues such as inequality, demographic changes, and the transition to a sustainable economy will be compromised if night is not considered. Recent years, however, have seen a surge in research into the night. We argue that “night studies” is on the cusp of coming into its own as an interdisciplinary field, and when it does, the field will consider questions that disciplinary researchers haven’t yet thought to ask.

Research on the coral-eating crown-of-thorns starfish (CoTS) has waxed and waned over the last few decades, mostly in accordance with the occurrence of population outbreaks at key locations, such as Australia’s Great Barrier Reef. This review considers advances in our understanding of the biology and ecology of CoTS based on the latest resurgence of research interest, which culminated in this current special issue on the Biology, Ecology and Management of Crown-of-Thorns Starfish. More specifically, this review considers progress against 41 specific research questions posed in the seminal review by P. Moran 30 years ago, as well as exploring new directions for CoTS research. Despite the plethora of research on CoTS (>1,200 research articles), there are persistent knowledge gaps that constrain effective management of outbreaks. Although directly addressing some of these questions will be extremely difficult, there have been considerable advances in understanding the biology of CoTS, if not the proximal and ultimate cause(s) of outbreaks. Moving forward, researchers need to embrace new technologies and opportunities to advance understanding of CoTS biology and behaviour, with focus given to key questions that will improve effectiveness of management to reduce the frequency and likelihood of future outbreaks, if not preventing them altogether.

Owing to the nondiffracting, self-accelerating, and self-healing properties, Airy beams of different nature have become a subject of immense interest in the past decade. Their interesting properties have opened doors to many diverse applications. Consequently, the questions of how to properly design spatial manipulation of Airy beams or how to implement them in different setups have become important and timely in the development of various optical devices. Here, based on our previous work, we present a short review on the spatial control of Airy beams, including the interactions of Airy beams in nonlinear media, beam propagation in harmonic potential, and the dynamics of abruptly autofocusing Airy beams in the presence of a dynamic linear potential. We demonstrate that under the guidance of nonlinearity and external potential, the trajectory, acceleration, structure, and even the basic properties of Airy beams can be adjusted to suit specific needs. We describe other fascinating phenomena observed with Airy beams, such as self-Fourier transformation, periodic inversion of Airy beams, and the appearance of spatial solitons in the presence of nonlinearity. These results have promoted the development of Airy beams, and have been utilized in various applications, including particle manipulation, self-trapping, and electronic matter waves.

Caveolin-1 (Cav-1) is 22 kDa caveolae protein, acts as a scaffold within caveolar membranes. It interacts with alpha subunits of G-protein and thereby regulates their activity. Earlier studies reported elevated or up-regulated levels of caveolin-1 in the serum of prostate cancer patients. Secreted Cav-1 promotes angiogenesis, cell proliferation and anti-apoptotic activities in prostate cancer patients. Cav-1 upregulation is mainly related to prostate cancer metastasis. Keeping above facts in view, the present study was designed to explore Cav-1 as a target for prostate cancer therapy using computational approach. Molecular docking, structural base molecular modelling and molecular dynamics simulations were performed to investigate Cav-1 inhibitors. A predictive model was generated and validated to establish a stable structure. ZINC database of biogenic compounds was used for induced fit docking (IFD) and high throughput virtual screening. The H-bond interactions of the compounds with active site residues of Cav-1 were estimated by IFD and 100 ns long molecular dynamic simulations. The reported compounds showed significant binding and thus can be considered as potent therapeutic inhibitors of Cav-1. This study provides a valuable insight into biochemical interactions of Cav-1 for therapeutic applications and warrants for experimental validation of the predicted ‘active(s)’.

Although long-term survival in Rett syndrome (RTT) has been observed, limited information on older people with RTT exists. We hypothesized that increased longevity in RTT would be associated with genetic variants in MECP2 associated with milder severity, and that clinical features would not be static in older individuals. To address these hypotheses, we compared the distribution of MECP2 variants and clinical severity between younger individuals with Classic RTT (under 30 years old) and older individuals (over 30 years old). Contrary to expectation, enrichment of a severe MECP2 variant (R106W) was observed in the older cohort. Overall severity was not different between the cohorts, but specific clinical features varied between the cohorts. Overall severity from first to last visit increased in the younger cohort but not in the older cohort. While some specific clinical features in the older cohort were stable from the first to the last visit, others showed improvement or worsening. These data do not support the hypothesis that mild MECP2 variants or less overall severity leads to increased longevity in RTT but demonstrate that clinical features change with increasing age in adults with RTT. Additional work is needed to understand disease progression in adults with RTT.

A new sustainable polypropylene terephthalate (PPT) coating was synthesized from recycled polyethylene terephthalate (PET) and applied on hydraulic concrete substrate to improve its durability. First step, PET bottles wastes were grinded and depolymerized by glycolysis using propylene glycol (PG), in a Vessel-type reactor (20–180 °C) to synthesize bis(2-hydroxypropyl)-terephthalate (BHPT), which was applied as coating to one-three layers on hydraulic concrete substrate, by brushing technique and polymerized (150 °C for 15 h) to obtain PPT. PET, BHPT and PPT were characterized by FT-IR, PET and PPT by TGA, and the PPT coatings by SEM (thickness), by ASTM-D3359-17 (adhesion) and by water contact angle (wettability). The durability of hydraulic concrete coated with PPT was studied by resist chloride ion penetration (ASTM-C1202-17), carbonation depth at 28 days (RILEM-CPC-18), and absorption water ratio (ASTM-C1585-20). The results demonstrated that the BHPT and PPT were synthetized (FT-IR), PPT had a similar thermal behaviour to PET (TGA); the PPT coatings had good adhesion to the substrate, with thicknesses of micrometric units; hydrophilic (similar to PET coatings), and the durability of hydraulic concrete coated with PPT (2-3 layers) improved (migration of chloride ions decreased, carbonation depth was negligible, and the absorption water ratio decreased).

Currently, obesity is a critical global public health burden. Numerous studies have demonstrated the regulation of the pathogenesis of obesity and metabolic abnormalities by the gut microbiota and microbial factors; however, their involvement in the various degrees of obesity is not yet understood well. Previously, obesity has been shown to be associated with decreased levels of vitamin B12. Considering exclusive microbial production of vitamin B12, we hypothesised that a decrease in cobalamin levels in obese individuals may be at least partially caused by its depleted production in the intestinal tract by the commensal microbiota. In the present study, our aim was to estimate the abundance of enzymes and metabolic pathways for vitamin B12 synthesis in the gut microbiota of mouse models of alimentary and genetically determined obesity, to evaluate the contribution of the obesogenic microbiome to vitamin B12 synthesis in the gut. We have defined a significantly lower representation of enzymes and metabolic pathways for vitamin B12 biosynthesis in obese mice compared to non-obese mice, wherein enzyme depletion was more pronounced in lepr(-/-) (db/db) mice, which developed severe obesity. The representation of enzymes involved in cobalamin synthesis is strongly correlated with representation of several microbes in high-fat diet fed mice, whereas there were almost no correlations in db/db mice. Therefore, the degree of obesity and the composition of the correspondent microbiota are the main contributors to the representation of genes and pathways for cobalamin biosynthesis in the mouse gut.

Platinum and taxane chemotherapy is associated with the risk of hypersensitivity reactions (HSRs), which may require switching to less effective treatments. Desensitization to platinum and taxane HSRs can be used to complete chemotherapy according to the standard regimen. Therefore, we aimed to investigate the current management of HSRs to platinum and/or taxane chemotherapy in patients with gynecologic cancers. We conducted an online cross-sectional survey among gynecological and medical oncologists consisting of 33 questions. A total of 144 respondents completed the survey and 133 respondents were included in the final analysis. Most participants were gynecologic oncologists (43.6%) and medical oncologists (33.8%), and 77.4% (n=103) were involved in chemotherapy treatment. More than 73% of participants experienced >5 HSRs to platinum and taxane per year. Pre-medication and a new attempt with platinum or taxane chemotherapy were used in 84.8% and 92.5% of Grade 1-2 HSR to platinum and taxane, respectively. In contrast, desensitization was used in 49.4% and 41.8% of Grade 3-4 HSR to platinum and taxane, respectively. Most participants strongly emphasized the need to standardize the management of platinum and taxane HSR in gynecologic cancer. Our study showed that HSR in gynecologic cancer is common, but management is variable and the use of desensitization is low. In addition, the need for guidance on the management of platinum- and taxane-induced HSR in gynecologic cancer was highlighted.

Candida albicans is present in oral health and has been linked with dental caries. So far, the behavior of the yeast in the presence of Streptococcus sanguinis has not been tested. The aim was to determine the effect of excess sugar as a cariogenic environment on the biological and physico-chemical parameters of single-species (C. albicans) and dual-species biofilms of C. albicans and S. sanguinis. An in vitro caries model was used. The biofilms were exposed to 10% sucrose or 0.9% NaCl for 5 min 3x/day/5 days. Viable cells, hyphal quantification, SEM, biofilm pH, H2O2 quantification and surface microhardness of enamel slabs were determined. Microbial viability and the number of hyphae were higher for sucrose exposure, in the dual-species biofilms induced by excess sugar and coexistence between the two microorganisms. Sucrose-exposed biofilms showed a progressive pH drop over the time course. H2O2 production was about 6 times higher for the dual-species biofilms. Enamel demineralization was higher in the single-species, suggesting an inhibitory effect due to S. sanguinis. Excess sugar increases the pathogenic potential of C. albicans biofilm. In dual-species biofilms, S. sanguinis prevents pronounced drops in pH, decreasing demineralization and stimulates the development of hyphae in the yeast.

The limited supply of drinking water has aroused people's curiosity in recent decades. Adsorption is a popular method for removing hazardous substances from wastewater, especially heavy metals, as it is cheap, highly efficient and easy to use. In this work, a new sludge-based activated carbon adsorbent (SBAC1 / SBAC2) was developed to remove hazardous metals such as cadmium (Cd+2) and lead (Pb+2) from an aqueous solution. The chemical structure and surface morphology of the produced SBAC1 and SBAC2 were investigated using a range of analytical tools such as CHNS, BET, FT-IR, XRD, XRF, SEM, TEM, N2 adsorption/desorption isothermal and zeta potential. BET surface areas were examined and SBAC2 was found to have a larger BET surface area (498.386 m2/g) than SBAC1 (336.339 m2/g). SBAC2 had a lower VBJH (1.5026 cm3 g-1) than SBAC1 (1.59873 cm3 g-1), but a higher VT (0.3748 cm3 g-1) than SBAC1 (0.2688 cm3 g-1), while the average pore size was 10-100 nm for SBAC1 and 45-50 nm for SBAC2. The ideal conditions investigated for the removal of Pb+2 and Cd+2 were 10 mg SBAC1 / SBAC2, Pb+2 / Cd+2 at an starting concentration of 30 mg/L, a temperature of 40 and 50 °C, pH = 6, 8 and contact times of 10 and 15 minutes for Pb+2 and Cd+2, respectively. SBAC1 and SBAC2 eliminated approximately 99.99% of Cd+2 and Pb+2 out the water under all conditions tested. The results of the adsorption of Cd+2 and Pb+2 were in good agreement with the pseudo-second-order equation (R2 = 1.00). Under the experimental conditions, the Cd+2 and Pb+2 adsorption equilibrium data were effectively linked to the Langmuir and Freundlich equations for SBAC1 and SBAC2, respectively. Langmuir model calculated the adsorption capacities of SBAC1 and SBAC2 for Cd+2 (309.24 and 329.62 mg/g) and for Pb+2 (318.46 and 339.61 mg/g), respectively. The regeneration showed high recyclability for the fabricated SBAC1 and SBAC2 during five consecutive reuse cycles. As a result, the produced SBAC1 and SBAC2 are attractive adsorbent for the elimination of heavy metals from various environmental and industrial wastewater samples.

Background: Liver failure profoundly affects the immune system, leading to dysregulation of innate and adaptive immune responses. Body: This review explores the intricate relationship between liver function and immune homeostasis. The role of the liver as a central hub in immune response initiation is elucidated, emphasizing its involvement in hepatic inflammation induction and subsequent systemic inflammation. Cytokines, chemokines, growth factors, and lipid mediators orchestrate these immune processes, serving as both prognostic biomarkers and potential therapeutic targets in liver failure-associated immune dysregulation. Furthermore, the review delves into the mechanisms underlying immunosuppression in liver failure, encompassing alterations in innate immune cell functions such as neutrophils, macrophages, and natural killer cells (NK cells), as well as perturbations in adaptive immune responses mediated by B and T cells. Conclusion: Understanding the immunological consequences of liver failure is crucial for developing targeted therapeutic interventions and improving patient outcomes in liver disease management.

Deep hypothermic circulatory arrest (DHCA) is safe, but subtle neurodevelopmental deficits may persist far beyond the perioperative period. We investigated the relationship between DHCA duration and neurodevelopmental outcomes in young children undergoing cardiac surgery with DHCA. Children aged &lt; 42 months, including neonates who underwent cardiac surgery using DHCA without regional perfusion techniques, were included as the DHCA group. Children in the same age range undergoing cardiac surgery without DHCA were included as the control group. All patients underwent neurodevelopmental assessment using the Bayley Scales of Infant and Toddler Development (BSTID) by a trained pediatrician. Seventeen of 25 DHCA and six of 10 control patients completed the BSTID assessment. The groups showed no preoperative, operative, or postoperative significant differences. In adjusted multivariable analysis, prematurity and age at assessment were significant changing predictors of each of the BSTID components (p &lt; 0.001), other than the gross motor component, where only age at assessment was a significant adjusting predictor. Longer DHCA was associated with lower fine and gross motor BSTID components; however, the association was not statistically significant (p = 0.06). Use of DHCA without regional perfusion techniques may be associated with less optimal neurodevelopmental outcomes if DHCA has a long duration.

The National Institute of Health Stroke Scale (NIHSS) is used worldwide to classify stroke severity as ‘mild’, ‘moderate’ or ‘severe’ based on neurological impairment. Yet stroke survivors argue that the classification of ‘mild’ does not represent the holistic experience and impact of stroke on their daily lives. In this observational cohort study, we aimed to identify different types of impairment among stroke survivors classified as mild. We used mild stroke survivors’ data from the START longitudinal stroke cohort (n=73) with measures related to sensorimotor, cognition, depression, functional disability, physical activity, work and social adjustment over 12 months. Given the multi-source, multi-granular and unlabelled nature of data, we utilised a structure-adapting, unsupervised machine learning approach, the Growing Self-organising Map (GSOM) algorithm to generate distinct clinical profiles. These diverse impairment profiles revealed that mild stroke survivors experience varying degrees of impairment and impact (cognitive, depression, physical activity, work/social adjustment) at different time points, despite the uniformity implied by their NIHSS-classified ‘mild’ stroke. This emphasises the necessity of creating a holistic and comprehensive representation of mild stroke survivors’ needs over the first-year post-stroke to improve rehabilitation and post-stroke care.

Cardiovascular complications are the major cause of diabetes-related morbidity and mortality. Increased renin-angiotensin-aldosterone system activity and decreased β-adrenergic receptor (β-AR) responsiveness contribute to diabetic cardiac dysfunction. We evaluated the effect of sacubitril/valsartan (neprilysin inhibitor plus angiotensin receptor antagonist combination), and valsartan treatments on the diabetic cardiac function through β-AR responsiveness, and on protein expression of diastolic components. 6-week-old male Sprague-Dawley rats were divided into control, diabetic, sacubitril/valsartan (68 mg/kg), and valsartan treated (31 mg/kg) diabetic groups. Diabetes was induced by high fat diet plus low dose streptozotocin (30 mg/kg, intraperitoneal). After 10 weeks of diabetes, rats were treated for 4 weeks. Systolic/diastolic function was assessed by in vivo echocardiography and pressure-volume loop analysis. β-AR mediated responsiveness was assessed by in vitro papillary muscle and Langendorff heart experiments. Protein expression of sarcoplasmic reticulum calcium ATPase2a, phospholamban, and phosphorylated phospholamban was determined by Western blot. Sacubitril/valsartan improved ejection fraction and fractional shortening to a similar extent as valsartan alone. None of the treatments affected in vivo diastolic parameters or expression of related proteins. β1-/β2-AR mediated responsiveness was partially restored in treated animals. β3-AR mediated relaxation responses were comparable among groups. The beneficial effect of sacubitril/valsartan on systolic function may be attributed to improved β1-/β2-AR responsiveness.

Neutrophil extracellular trap formation has been identified as a new cell death mediator, termed NETosis, which is distinct from apoptosis and necrosis. NETs capture foreign substances, such as bacteria, by releasing DNA into the extracellular environment, and have been associated with inflammatory diseases and altered immune responses. Short-chain fatty acids, such as acetate, are produced by the gut microbiota and reportedly enhance innate immune responses; however, the underlying molecular mechanisms remain unclear. Here, we investigated the effects of sodium acetate, which has the highest SCFA concentration in the blood and gastrointestinal tract, on NETosis by focusing on the mechanisms associated with histone acetylation in neutrophil-like HL-60 cells. Sodium acetate enhanced NETosis as shown by fluorescence staining with SYTOX green, and the effect was directly proportional to the treatment duration (16–24 h). Moreover, the addition of sodium acetate significantly enhanced the acetylation of Ace-H3, H3K9ace, H3K14ace, and H3K27ace. Sodium acetate-induced histone acetylation rapidly decreased upon stimulation with the calcium ionophore A23187, whereas histone citrullination markedly increased. These results demonstrate that sodium acetate induces NETosis via histone acetylation in neutrophil-like HL-60 cells, providing new insights into the therapeutic effects based on the innate immunity-enhancing effect of dietary fiber.

Background: Intrauterine transfusion (IUT) of the donor and partial exchange (pET) of the recipient is a temporizing treatment for pregnancies with Twin Anemia Polycythemia Sequence (TAPS). We sought to give a detailed description of the procedural approach and outcomes for sequential donor IUT and recipient pET in TAPS. Methods: Retrospective study of spontaneous TAPS referred to the Johns Hopkins Center for Fetal Therapy treated with donor IUT followed by recipient pET utilizing a double-syringe set up. Procedure characteristics and outcomes as well as accuracy of existing transfusion formulas were analyzed and compared with the literature. Results: 5 of 78 patients with spontaneous TAPS underwent a total of 19 combined IUT/pET procedures (median first procedure to delivery interval 5.6 weeks [interquartile range IQR 1.9-6.0]). One pET was stopped for fetal decelerations. Patients delivered at 33.0 weeks [IQR 31.9-33.3] with two survivors and no neonatal transfusion requirements. IUT volumes were 48 ml [IQR 39-63 ml] and pET volumes 32 ml [IQR 20-50] utilizing aliquots of 5 – 20 mls for the latter (p=0.021). For IUTs, assumption of a fetal blood volume below 150 ml/kg underestimated required transfusion volume. For pETs, all formulas required adjustment of dilution volume based on bedside testing (p&lt;0.05 for all). Conclusions: Donor transfusion followed by partial exchange in the recipient can prolong pregnancy in spontaneous TAPS and obviate the need for neonatal transfusion. A double-syringe setup facilitates efficient saline exchange. Because the accuracy of volume formulas is limited, bedside testing is recommended to achieve the target hemoglobin.

Phytochemicals have a long and successful history in drug discovery. With recent advancements in analytical techniques and methodologies, discovering bioactive leads from natural compounds has become easier. Computational techniques like molecular docking, QSAR modelling and machine learning, and network pharmacology are among the most promising new tools that allow researchers to make predictions concerning natural products' potential targets, thereby guiding experimental validation efforts. Additionally, approaches like LC-MS or LC-NMR speed up compound identification by streamlining analytical processes. Integrating structural and computational biology aids in lead identification, thus providing invaluable information to understand how phytochemicals interact with potential targets in the body. Emerging computational approach is machine learning involving QSAR modelling and deep neural networks that interrelate phytochemical properties with diverse physiological activities such as antimicrobial or anticancer effects.