Chitosan is a biodegradable polymer derived from chitin, that is a versatile material for various biological applications for its attractive properties such as biocompatibility, biodegradability, and non-toxicity. Furthermore, chitosan possesses Second Harmonic Generation properties, that are useful for bio-sensing applications. In this work we explored the possibility to exploit chitosan-based nanospheres as SHG-based bio-sensors, and also as carriers of 89Sr radionuclide, an Active Pharmaceutical Ingredient for radiopharmaceutical treatments in cancer therapy. To load opportunely the Sr ion on the nanospheres, we used a fructose-based Metal Organic Framework, of formula [Sr(C6H12O6)2(H2O)2]Cl2·H2O, because the sugar was able to drive the Sr ions on the chitosan matrix. The Sr-loaded chitosan nanospheres were synthetized, characterized, and their SHG response was measured. The results encouraged us to propose the nanospheres for theranostic purposes, i.e. at the same time valuable for both therapy and diagnostic applications.

Knowledge of the genetic diversity of the available germplasm is an important foundation for crop conservation, management, and improvement. Successful breeding strategies rely on a sound understanding of the genetic diversity of the crop germplasm. This study was conducted to evaluate and compare the genetic diversity of 49 soybean [Glycine max (L.) Merrill] genotypes using SSR markers as well as to evaluate parental potential of these genotypes in cultivar improvement. The bulk of the genotypes were developed in the national soybean breeding program in Zimbabwe between 1940 and 2013. The genetic diversity and relatedness were estimated using 30 SSR markers and produced 5 clusters that generally matched the pedigree information of the germplasm. The SSR analysis detected a total of 135 alleles. The polymorphic information content ranged from 0.10 to 0.77 with a mean of 0.45. The SSR primer, Satt012 was the most informative. The SSR marker analysis showed a wide genetic diversity in the germplasm. To date, there are no reports regarding the genetic diversity analysis of soybean germplasm in Zimbabwe. The genotypes, EL41 and EL7; EL41 and EL1; as well as EL41 and EL42 were the most divergent thus, indicating their potential use as parental lines in the genetic improvement of soybean in the region.

Despite substantial evidence supporting the efficacy of prebiotics for promoting host health and stress resilience, few experiments present evidence documenting the dynamic changes in microbial ecology and fecal microbial-modified metabolites across time. Furthermore, the literature reports a lack of reproducible effects of prebiotics on specific bacteria and bacterial-modified metabolites. The current experiments examined whether consumption of diets enriched in prebiotics (galactooligosaccharides, GOS and polydextrose, PDX) compared to control diet, would consistently impact the gut microbiome and microbial-modified bile acids across time and between two research sites. Male Sprague Dawley rats were fed control or prebiotic diets for several weeks, and their gut microbiome and metabolome were examined using 16S rRNA gene sequencing and untargeted LC-MS/MS analysis. Dietary prebiotics altered beta diversity, relative abundances of bacterial genera, and microbially modified bile acids across time. PICRUSt2 analyses identified four inferred functional metabolic pathways modified by prebiotic diet. Correlational network analyses between inferred metabolic pathways and microbial-modified bile acids revealed deoxycholic acid as a potential network hub. All these reported effects were consistent between the two research sites supporting the conclusion that dietary prebiotics robustly changed the gut microbial ecosystem. Consistent with our previous work demonstrating that GOS/PDX reduces the negative impacts of stressor exposure, we propose that ingesting a diet enriched in prebiotics facilitates the development of a health-promoting gut microbial ecosystem.

Hemoglobinopathies are a group of disorders in which the hemoglobin molecule has abnormal production or structure. The hemoglobin molecules in red blood cells (RBC) are impacted by the blood disease known as sickle cell disease (SCD), and Thalassemia is one of the major monogenic disorders that reduces hemoglobin production( Kohne et al ., 2011). This disorder results in a large number of red blood cells being destroyed, leading to anemia. India bears a huge burden of hemoglobinopathies; thalassemia is the most prevalent (Mondal SK et al., 2016). A key component of thalassemia prevention is a successful screening procedure to identify Thalassemia carriers. Effective screening programs have numerous obstacles, especially in environments with limited resources. Machine learning (ML) has been used to solve technical and domain-specific problems in a variety of prognostic and diagnostic medical jobs. In this work, we aimed to identify and analyze the most common mutation of β--thalassemia and sickle cell disease from the north Indian population by employing Machine learning-based algorithms. To accurately predict the carrier state from a simple blood test, and to predict pathogenic hemoglobin variants in a group of individuals, these results demonstrate the application of integrated bioinformatics and machine learning approaches. This study contributes to the validation of the models based on data from several individuals and hemoglobinopathies.

This manuscript reviews two decades of projects funded by the Kirkhouse Trust (KT), a charity registered in the UK. KT was established to improve the productivity of legume crops important in African countries and in India. KT’s requirements for support are: 1) the research must be done by national scientists in their home institution, either a publicly funded agricultural research institute or a university; 2) the projects need to include a molecular biology component, which to date has mostly comprised the use of molecular markers for the selection of one or more target traits in a crop improvement programme; 3) the projects funded are included in consortia, to foster the creation of scientific communities and the sharing of knowledge and breeding resources. This account relates to the key achievements and challenges, reflects on the lessons learned and outlines future research priorities.

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

Groundwater represents a pivotal asset in conserving natural water reservoirs for potable consumption, irrigation, and diverse industrial uses. Nevertheless, human activities intertwined with industry and agriculture contribute significantly to groundwater contamination, highlighting the critical necessity to appraise water quality for safe drinking and effective irrigation. This research primarily focused on employing the Water Quality Index (WQI) to gauge water's appropriateness for these purposes. However, the generation of an accurate WQI can prove time-intensive owing to potential errors in sub-index calculations. In response to this challenge, an artificial intelligence (AI) forecasting model was devised, aiming to streamline the process while mitigating errors. The study collected 422 data samples from Mirpurkash, a city nestled in the province of Sindh, for a comprehensive exploration of the region's WQI attributes. Furthermore, the study probed into unraveling the interdependencies amidst variables in the physiochemical analysis of water. Diverse machine learning classifiers were employed for WQI prediction, with findings revealing that random forest and gradient boosting eclipsed other algorithms, achieving an accuracy rate of 99%. In close pursuit were SVM and XGBoost, registering accuracy scores of approximately 95% and 93%, respectively, while KNN and Decision Trees garnered accuracy rates of 88% and 87%, respectively. In addition to WQI prediction, the study conducted an uncertainty analysis of the models using the R-factor, providing insights into the reliability and consistency of predictions. This dual approach, combining accurate WQI prediction with uncertainty assessment, contributes to a more comprehensive understanding of water quality in Mirpurkash and enhances the reliability of decision-making processes related to groundwater utilization

Purpose: The study investigates soil pores' impact on carbon dynamics and sequestration processes, examining their physical and chemical characteristics and their mechanisms for carbon sequestration.Research Method: Existing literature and research on soil pores, carbon dynamics, and carbon sequestration are analyzed. The interrelationships between soil pore structure, water movement, microbial activity, root penetration, carbon input, soil aggregation, and gas exchange are examined. Traditional techniques and advanced imaging methods are used to quantify and characterize soil pores.Findings: Soil pores play a critical role in facilitating carbon sequestration through various mechanisms. They affect water movement, microbial activity, root penetration, carbon input, soil aggregation, and gas exchange. Understanding these relationships is crucial for sustainable soil management.Research Limitations: This study relies on existing literature and research, which may have limitations and uncertainties. Further research is needed to address these gaps and enhance understanding.Originality Value: This research enhances the existing knowledge by comprehensively examining the significance of soil pores in carbon dynamics and sequestration. It incorporates both traditional and advanced methods, providing insights for soil management and contributing to climate change mitigation efforts.

Ambitious biodiversity goals to protect 30% or more of the Earth’s surface by 2030 (30x30) require strategic near-term targets. To define areas that must be protected to prevent the most likely and imminent extinctions, we propose Conservation Imperatives—16,825 unprotected sites harboring rare and threatened species and spanning ~164 Mha of the terrestrial realm. We estimate that protecting the Conservation Imperatives would cost approximately US$169 billion [90% probability: $146 — $228 billion]. Globally, 38% of the 16,825 sites are either adjacent to or within 2.5 km of an existing protected area, potentially reducing land acquisition and management costs. These sites should be prioritized for conservation action over the next five years as part of a broader strategy to expand the global protected area network. The expansion of global protected areas between 2018–2023 incorporated only 7% of sites harboring range-limited and threatened species, highlighting a renewed urgency to conserve these habitats. Permanently protecting only 0.74% of land found in the tropics, where Conservation Imperatives are concentrated, could prevent the majority of predicted near-term extinctions once adequately resourced. We estimate this cost to be US$29 billion to US$46 billion per year over the next five years. Multiple approaches will be required to meet long-term protection goals: providing rights and title to Indigenous Peoples and Local Communities (IPLCs) conserving traditional lands, government designation of new protected areas on federal and state lands, and land purchase or long-term leasing of privately held lands.

This study focuses on land cover and land management changes in relation to food security and environmental services in a semi-arid area of East Nusa Tenggara (ENT) – Indonesia. The study was conducted in Central Sumba District of ENT Province. Classification and regression tree (CART) for land cover classification has been analyzed using machine learning techniques using Google Earth Engine. A survey with Focus Group Discussion (FGD) and followed with in-depth interviews were conducted for primary data collection involving a total of 871 respondents. The Socio-economic data analyzed statistics descriptively and non-parametric tests. The study showed that: 1). There has been a substantial land use change during the devo-lution era that has both positive and negative implications for food security and envi-ronmental services. 2). There has been population pressure in the fertile or agricultur-al land as the direct impact of the development of city infrastructures; and 3). Nation-al intervention through the Food Estate program has fostered and shaped land use change and land management in Central Sumba District. The study highlights the importance that the devolution spirit should help to well manage the limited ara-ble/agricultural land in dominated semi-arid to ensure food security and environment services.

Objective: We determined, in stable ambulatory heart failure with reduced ejection fraction (HFrEF) subjects and matched controls, the capability of a novel blood based cardiac-specific cBIN1 Score (CS), which assesses the health of cardiac muscle, to identify patients with known heart failure (HF) and to prognosticate future hospitalization. Background: Limited clinical tools are available in assessing cardiac muscle health in stable ambulatory patients. Cardiac bridging integrator 1 (cBIN1) is a cardiomyocyte t-tubule membrane scaffolding protein which regulates calcium signaling in cardiomyocytes, decreases in failing muscle, and is present in plasma in levels that correlate with cardiac content. We hypothesize that CS, a normalized index of plasma cBIN1 concentration, can function as a diagnostic and prognostic biomarker of HF. Methods: Plasma cBIN1 concentration is measured by an ELISA test, and CS is calculated as the natural log of the ratio of a constant population mean cBIN1 to measured cBIN1 concentration. We determined CS among 125 clinically stable individuals with HFrEF (LVEF ≤ 40%) (mean age 56 ± 10 years old, 79% men) and 125 age, sex matched volunteers with no known history of HF. We obtained plasma concentrations of NT-proBNP, a marker of volume status, as comparison. Baseline co-morbidities and 18-month longitudinal clinical information were obtained through electronic medical records. Results: CS follows a normal distribution with a median of 0 in the control population and median is significantly increased among HFrEF patients to 1.8 (IQR 1.4 – 2.1, p < 0.0001). CS diagnosed HFrEF with a receiver operating characteristic (ROC) area under the curve (AUC) of 0.93 (AUC is 0.98 for NT-proBNP, and combined CS and NT-proBNP AUC is 0.99). Unlike NT-proBNP, CS does not correlate with body mass index (BMI) in either the control or HFrEF population (Pearson’s r = -0.15, p = 0.12; Pearson’s r = 0.003, p = 0.97, respectively). NT-proBNP significantly correlates with renal function (Pearson’s r = -0.37, p = 0.001), while CS also has no correlation (Pearson’s r = 0.03, p = 0.71). During an 18-month follow-up, a high CS ≥ 1.8 at the initial visit predicted future cardiovascular hospitalizations (38% vs. 21%, p = 0.04, hazard ratio 2.0). NT-proBNP did not predict future cardiovascular hospitalizations. Conclusions: Plasma cBIN1 based CS is insensitive to BMI and renal function and differentiates myocardial health between patients with HFrEF versus matched controls. An abnormally high CS reflected poor intrinsic myocardial health and can predict future 18-month cardiac hospitalization in stable ambulatory patients.

Solanesol is a noncyclic terpene alcohol composed of nine isoprene units and it mainly accumulates in solanaceous plants, especially tobacco (Nicotiana tabacum L.). Here, RNA-seq analyses of tobacco leaves, stems, and roots were used to identify solanesol biosynthesis genes. Six 1-deoxy-d-xylulose 5-phosphate synthase, two 1-deoxy-d-xylulose 5-phosphate reductoisomerase, two 2-C-methyl-d-erythritol 4-phosphate cytidylyltransferase, four 4-diphosphocytidyl-2-C-methyl-d-erythritol kinase, two 2-C-methyl-d-erythritol 2,4-cyclodiphosphate synthase, four 1-hydroxy-2-methyl-2-(E)-butenyl 4-diphosphate synthase, two 1-hydroxy-2-methyl-2-(E)-butenyl 4-diphosphate reductase, six isopentenyl diphosphate isomerase, and two solanesyl diphosphate synthase (SPS) genes were identified to be involved in solanesol biosynthesis. Furthermore, the two N. tabacum SPS (NtSPS1 and NtSPS2), which had two conserved aspartate-rich DDxxD domains, were highly homologous with SPS enzymes from other solanaceous plant species. In addition, the solanesol contents of three organs, and leaves from four growing stages, corresponded with the distribution of chlorophyll. Our findings provide a comprehensive evaluation of the correlation between the expression of different biosynthetic genes and the accumulation of solanesol in tobacco.

The efficacy and cost-effectivness of Multigene Panel Next-Generation Sequencing (NGS) in directing patients towards genomically matched therapies remains uncertain. This study investigated metastatic colorectal cancer (mCRC) patients who underwent NGS analysis on formalin-fixed paraffin-embedded tumor samples. Data from 179 patients were analyzed, revealing no mutations in 39 patients (21.8%), one mutation in 83 patients (46.4%), and two or more mutations in 57 patients (31.8%). KRAS mutations were found in 87 patients (48.6%), including KRAS G12C mutations in 5 patients (2.8%), PIK3CA mutations in 40 patients (22.4%), BRAF mutations in 26 patients (14.5%). Less common mutations were identified: ERBB2 in 5 patients (2.8%) and SMO in 4 patients (2.2%). Additionally, MAP2K1, CTNNB1, and MYC were mutated in 3 patients (2.4%). Two mutations (1.1%) were observed in ERBB3, RAF1, MTOR, JAK1, and FGFR2. No significant survival differences were observed based on mutation numbers. 40% of patients had druggable molecular alterations, but only 1.1% received genomically guided treatment, suggesting limited application in standard practice. Despite this, expanded gene panel testing can identify actionable mutations, aiding personalized treatment strategies in metastatic CRC, although current eligibility for biomarker-guided trials remains limited.

A convenient and efficient strategy for the preparation of 2-sulfonylindoles has been achieved through iodophor/H2O2-mediated 2-sulfonylation of indoles with readily available sulfonyl hydrazides in aqueous phase. Iodophor is commercially available and serves as the green catalyst and aqueous phase. A series of 2-sulfonylated products from indoles and N-methylpyrrole were synthesized in moderate yields in only 10 min. Control experiments were also conducted to reveal the mechanism. This method is environment friendly, easy to operate and suitable for a wide range of substrates.

Fatigue performance and self-repairing activity of asphalt binders are two properties that highly influence the fatigue cracking response of asphalt pavement. There are still numerous gaps of knowledge to fill linked with these two characteristics. For instance, current parameters fail to fully accommodate these two bitumen phenomena. This study aims to propose a new procedure to address this issue utilizing the linear amplitude sweep (LAS) test, LAS with rest period (RP) (LASH) test, and simplified viscoelastic continuum damage (S-VECD) model. This research work used four different types of asphalt binders: neat asphalt (NA), self-healing thermoplastic polyurethane (STPU)-modified bitumen (STPB), self-healing poly (dimethyl siloxane) crosslinked with urea bond (IPA1w)-modified bitumen (IPAB), and styrene–butadiene–styrene (SBS)-modified bitumen (SBSB). Before the testing process, all the materials were subjected to short-term and long-term aging. The new procedure showed a superior capacity to analyze and accommodate all bitumen fatigue performances and self-repairing activities compared to the current method. Another finding proved that asphalt binders with higher self-restoration behavior failed to show better fatigue performance. A breakthrough finding demonstrated that asphalt binder fatigue response augmented when the RP was applied at a higher damage intensity (S) value. STPBs and IPABs reached their highest increments of fatigue response, containing 1.0% of STPU and 0.5% of IPA1w, respectively. Those augmentations were 207.54% and 232.64%, respectively.

Sepsis still remains one of the most difficult conditions to diagnose as it presents unspecific clinical signs and symptoms, which makes early detection crucial. Our study aimed to enhance the accuracy of sepsis diagnosis by integrating multimodal monitoring technologies with traditional diagnostic methods. The research involved 121 newborns, comprising 39 cases of late-onset sepsis, 35 cases of early-onset sepsis, and 47 control subjects. Biosignals including pulse oximetry (PO), near-infrared spectroscopy (NIRS), and skin temperature (ST) were continuously monitored and an algorithm was developed using Python for identifying early signs of sepsis. The model demonstrated the ability to detect sepsis 6 to 48 hours in advance with an accuracy rate of 87.67% ± 7.42%. Sensitivity and specificity were recorded at 76% and 90%, respectively, with NIRS and ST having the most significant impact on predictive accuracy. Despite the promising results, limitations such as sample size, data variability, and potential biases were noted. The findings highlight the critical role of non-invasive biosensing methods in conjunction with traditional biomarkers and cultures, offering a robust framework for early sepsis detection and improved neonatal care. Further studies are recommended to validate these results across diverse clinical settings.

Hazelnut shells (HS), scientifically known as Corylus avellana L. shells, are a waste produced in companies that process nuts. The main objective of this study was to find an efficient way to maximize the chemical potential of HS by solubilizing the hemicelluloses, which could then be used to recover sugars and at the same time increase the lignin content of this material in order to produce adhesives or high strength foams. In order to optimize the pre-hydrolysis process, two different temperatures (160 and 170 C) and times varying from 15 to 180 min were tested. All the remaining solid materials were then liquefied by polyalcohols with acid catalysis. The chemical composition of hazelnut shells was determined before and after the pre-hydrolysis. All the process was monitored by FTIR-ATR by determining the spectra of solids and liquids after pre-hydrolisis and liquefactions steps. The highest solubilization of hazelnut shells was found for 170 C and 180 min, resulting in a 25.8% solubilization. Chemical analysis after the hydrolysis process showed a gradual increase in the solubilization of hemicelluloses as both the temperature and time of the reactor were increased. Simultaneously, the percentages of α-cellulose and lignin in the material also increased with rises in temperature and duration. FTIR-ATR allowed for the detection of significant spectral changes in the hazelnut shells from their initial state to the solid residue and further into the liquefied phase. This confirmed that pre-hydrolysis was effective in enhancing the chemical composition of the material, making it more suitable for the production of adhesives or polyurethane foams with enhanced mechanical strength.

Uropathogenic E. coli (UPEC) is the main etiologic agent of urinary tract infections (UTI) and possesses virulence and resistance determinants commonly harbored in mobilizable genetic elements such as plasmids or pathogenicity islands (PAI). UPEC belongs to the group of Ex-traintestinal pathogenic E. coli, however the existence of hybrid strains has been described; these possess both diarrheagenic (DEC) and extraintestinal (ExPEC) E. coli traits and are considered as "hypervirulent strains," which represents a significant health problem. This study aimed to de-termine the prevalence of UPEC PAI, ExPEC sequence types (ST), DEC genes, carbapenemase and extended-spectrum β-lactamase (ESBL) phenotypes, fluoroquinolones/aminoglycosides resistance genotypes and the presence of plasmids in 40 clinical isolates previously characterized as UPEC. A 72.5% of the isolates presented PAI, mainly PAI IV536 (53%). Sixty-five percent of the β-lactam-resistant isolates were positive for ESBL phenotype, and 100% of the car-bapenem-resistant isolates were carbapenemase producers. The most prevalent ESBL-associated gene was blaCTX-M-2 (60%), while among isolates resistant to fluoroquinolones and aminoglycosides the most frequent resistance gene was aac(6')Ib (93%). Plasmid bands were present in 57% of the isolates. Seventy percent belonged to the ST131 clonal group. The presence of molecular markers associated with DEC pathotypes was detected in 20 isolates; 60% were classified as hybrid pathotypes. These data suggest, in addition to an important pathogenic potential, the existence of hybrid pathotypes in clinical isolates of E. coli causing UTI in the Mexican population.

Pyrazinacenes are linearly fused heteroaromatic rings, with N atoms replacing all apical CH moieties. Component rings may exist in a reduced state having NH groups instead of N, causing cross-conjugation. These compounds have interesting optical and electronic properties, including strong fluorescence in the near infrared region and photocatalytic properties, leading to diverse possible applications in bio-imaging, organic synthesis as well as obvious molecular electronic uses. In this study, we have investigated the behaviour of seven-ring pyrazinacene 2,3,11,12-tetraphenyl-7,16-dihydro-1,4,5,6,7,8,9,12,13,14,15,16,17,18-tetradecaazaheptacene (Ph4H2N14HEPT) with emphasis on protic processes including oxidation, tautomerism, deprotonation and protonation, and the species resulting from those processes. We have used computational methods to optimize the structures of the different species and generate/compare molecular orbital structures. Aromaticity of species generated by the different processes has been assessed using the nucleus independent chemical shifts, and trends in the values have been associated with the different transformations of the pyrazinacene core. The computational data was compared with experimental data obtained from synthetic samples of the molecule tBu8Ph4H2N14HEPT.

Unmanned vehicles (UVs) have become increasingly important in various scenarios of civil and military operations. The present work aims at the conceptual design of a modular Amphibious Unmanned Ground Vehicle (A-UGV), that can be easily adapted for different types of land and/or water missions, with low monetary cost (&lt;5k€, without sensors). Basing the design on the needs highlighted in the 2021 review of the Strategic Directive of the Portuguese Navy, the necessary specifications and requirements are established for two mission scenarios. Then a market research analysis focused on vehicles currently available, and their technological advances, is conducted to identify existing UVs solutions and respective characteristics/capabilities of interest to the current work. To study and define the geometry of the hull and the configuration of the A-UGV itself, preliminary computational structural and fluid analyses are carried out to ensure it complies with the specifications initially established. As a result, one obtains a fully electric vehicle, with approximate dimensions of 1050×670×450mm (length-width-height), enabled with 6×6 traction capable of reaching 20km/h in land, possesses amphibious capabilities of independent propulsion in water up to 8kts, and with an estimated autonomy of over 60 minutes.

Genetic variability in rice breeding program plays the very crucial role. It provides outstanding pool of superior alleles governing better agronomic and quality characters through association mapping. For the understanding of population structure and genetic relationship among the different rice lines is indispensable prior to setting of correlation among dynamic alleles and traits. In the present investigation, genetic diversity and population structure of 116 rice accessions by using 64 polymorphic SSR markers was targeted for the evaluation of the genetic relatedness and diversity. Genotyping assessment based on SSR markers revealed a total of 225 alleles, with an average PIC value of 0.755. The germplasm lines were classified into three distinct subgroups through population structure analysis, utilizing both model and distance-based approaches. AMOVA analysis showed that 11% of the total variation could be attributed to differences between groups, while the remaining 89% of the variation was likely due to differences within groups. The study suggests that the population structure and genetic relatedness should be considered when working with the core collection of 116 rice germplasm lines for association mapping, aiming to establish marker-trait associations.

The cancer burden is increasing worldwide with contrasting national patterns. Therefore, providing national estimations is necessary to understand and control this health issue. Herein, we comparatively describe incidence, mortality, and disability-adjusted lived years (DALYs) due to 29 groups of cancer in Mexico from 1990 to 2019 by sex and age. Using public data from the Global Burden of Disease Study 2019, we assessed the national burden of cancer using counts and crude and age-standardized rates per 100,000 people with 95% uncertainty intervals for 2019 and their trends using the annual percentage of change from 1990 to 2019. In 2019, cancer caused 222,060 incident cases, 105,591 deaths, and 2,86,054 DALYs in the general population. Nonmelanoma skin cancer, prostate cancer, and breast cancer had the highest incidence, and six groups of cancer (lung, colorectal, stomach, prostate, breast, and pancreatic) caused 53% of the deaths in 2019. From 1990 to 2019, incidence and mortality showed an increasing trend that varied between 10% and 436% among the groups of cancer, whereas the crude and age-standardized rates showed cancer-specific sex disparities. Our results demonstrate a substantial growth of the national burden of cancer with sex-specific patterns of change. These results may guide national efforts toward reducing health loss due to cancer.

Background: Application of enhanced recovery after surgery principles decrease postoperative complications (POCs), length of stay (LOS), and readmissions. Pharmacoprophylaxis decreases morbidity, but the effect of specific regimens on clinical outcomes is unclear. Methods and Materials: Records of 476 randomly selected adult patients who underwent elective colorectal surgeries (ECRS) at 10 US hospitals were abstracted. Primary outcomes were surgical site infection (SSI), venous thromboembolism (VTE), postoperative nausea and vomiting (PONV), pain, and ileus rates. Secondary outcomes included LOS and 7- and 30-day readmission rates. Results: POC rates were SSI (3.4%), VTE (1.5%), PONV (47.9%), pain (58.1%), and ileus (16.1%). Cefazolin 2g/metronidazole 500mg and ertapenem 1g were associated with the shortest LOS; cefotetan 2g and cefoxitin 2g with the longest LOS. No SSI occurred with ertapenem and cefotetan. More Caucasians than Blacks received oral antibiotics before intravenous antibiotics without impact. Enoxaparin 40 mg subcutaneously daily was the most common inpatient and discharge VTE prophylaxis. All in-hospital VTEs occurred with unfractionated heparin. Most received rescue rather than around the clock antiemetics. Scopolamine patch, spinal opioids, and IV lidocaine continuous infusion were associated with lower PONV. Transversus abdominis plane block with long-acting local anesthetics, celecoxib, non-anesthetic ketamine bolus, ketorolac IV, lidocaine IV, and pregabalin were associated with lower in-hospital pain severity rate. Gabapentinoids and alvimopan were associated with lower ileus rate. Acetaminophen, alvimopan, famotidine, and lidocaine patch were associated with shorter LOS. Conclusions: Significant differences in pharmacotherapy regimens that may improve primary and secondary outcomes in ECRS were identified. Future research should identify latent pharmacotherapy variables that impact patient outcomes.

Efforts towards an effective HIV-1 vaccine have remained mainly unsuccessful. There is increasing evidence for a potential role of HLA-C-restricted CD8+ T cell responses in HIV-1 control, including our recent report of HLA-C*03:02 among African children. However, there are no documented optimal HIV-1 CD8+ T cell epitopes restricted by HLA-C*03:02; additionally, the structural influence of HLA-C*03:02 on epitope binding is undetermined. Immunoinformatics approaches provide a fast and inexpensive method to discover HLA-restricted epitopes. Here, we employed immunopeptidomics to identify HLA-C*03:02-restricted CD8+ T cell epitopes. We identified a clade-specific Gag-derived GY9 (GTEELRSLY) HIV-1 p17 matrix epitope exclusively restricted to HLA-C*03:02. Residues E62, T142, and E151 in the HLA-C*03:02 binding groove and positions p3, p6, and p9 on the GY9 epitope are crucial in shaping and stabilizing the epitope binding. Our findings support the growing evidence of the contribution of HLA-C molecules to HIV-1 control and provide a prospect for vaccine strategies.

The model organism Drosophila melanogaster has become a focal system for investigations of rapidly evolving genital morphology as well as the development and functions of insect reproductive structures. To follow up on a previous paper outlining unifying terminology for the structures of the male terminalia in this species, we offer here a detailed description of the female terminalia of D. melanogaster. Informative diagrams and micrographs are presented to provide a comprehensive overview of the external and internal reproductive structures of females. We propose a collection of terms and definitions to standardize the terminology associated with the female terminalia in D. melanogaster and we provide a correspondence table with the terms previously used. Unifying terminology for both males and females in this species will help to facilitate communication between various disciplines, as well as aid in synthesizing research across publications within a discipline that has historically focused principally on male features. Our efforts to refine and standardize the terminology should expand the utility of this important model system for addressing questions related to the development and evolution of animal genitalia, and morphology in general.

The dimensional effect of the accumulation of an electric charge with a density of up to 270 μF/g by the system of compacted zirconium dioxide nanoparticles during exposure in an electric field (5000 V/m) under normal physical conditions is determined. Based on a qualitative complex analysis of the forms of appearance of the effect, it is shown that the place of localization of different charge carriers is the surface of nanoparticles. The supposed mechanism of this effect is considered using the theory of dispersed systems, the band theory, and the theory of contact phenomena in semiconductors. It was concluded that this mechanism is due to the phenomenon of localization of electron-type charge nanoparticles in the near-surface zone of the material in contact with the adsorption ion atmosphere. This effect is relevant for modern nanoelectronics, microsystem technology, and printed electronics.

Outbreaks of Ebola ebolavirus (EBOV) have been associated with high morbidity and mortality. Milestones have been reached recently in the management of EBOV disease (EVD) with licensure of an EBOV vaccine and two monoclonal antibody therapies. However, neither vaccines nor therapies are available for other disease-causing filoviruses. In preparation for such outbreaks, and for more facile and cost-effective management of EVD, we seek a cocktail containing orally available and room temperature stable drugs with strong activity against multiple filoviruses. We previously showed that (bepridil + sertraline) and (sertraline + toremifene) synergistically suppress EBOV in cell cultures. Here we describe steps towards testing these combinations in a mouse model of EVD. We identified a vehicle suitable for oral delivery of the component drugs and determined that, thus formulated the drugs are equally active against EBOV as preparations in DMSO, and they maintain activity upon storage in solution for up to seven days. Pharmacokinetic (PK) studies indicated that the drugs in the oral delivery vehicle are well tolerated in mice at the highest doses tested. Collectively the data support advancement of these combinations to tests for synergy in a mouse model of EVD. Moreover, mathematical modeling based on human oral PK projects that the combinations would be more active in humans than their component single drugs.

We put forward a co-axial pump(optical)-probe(X-rays) experimental concept and show performance of the optical component. A Bessel beam generator with a central 100 micrometers-diameter hole (on the optical axis) was fabricated using femtosecond (fs) laser structuring inside a silica plate. This flat-axicon optical element produces a needle-like axial intensity distribution which can be used for the optical pump pulse. The fs-X-ray free electron laser (X-FEL) beam of sub-1 micrometer diameter can be introduced through the central hole along the optical axis onto a target as a probe. Different realisations of optical pump are discussed. Such optical elements facilitate alignment of ultra-short fs-pulses in space and time and can be used in light-matter interaction experiments at extreme energy densities on the surface and in the volume of targets. Full advantage of ultra-short 10 fs X-FEL probe pulses with fs-pump(optical) opens an unexplored temporal dimension of phase transitions and the fastest laser-induced rates of material heating and quenching. A wider field of applications of fs-laser-enabled structuring of materials and design of specific optical elements for astrophotonics is presented.

In an era of rapid global change, our ability to understand and predict Earth's natural systems is lagging behind our ability to monitor and measure changes in the biosphere. Bottlenecks in our ability to process information have reduced our capacity to fully exploit the growing volume and variety of data. Here, we take a critical look at the information infrastructure that connects modeling and measurement efforts, and propose a roadmap that accelerates production of new knowledge. We propose that community cyberinfrastructure tools can help mend the divisions between empirical research and modeling, and accelerate the pace of discovery. A new era of data-model integration requires investment in accessible, scalable, transparent tools that integrate the expertise of the whole community, not just a clique of ‘modelers’. This roadmap focuses on five key opportunities for community tools: the underlying backbone to community cyberinfrastructure; data ingest; calibration of models to data; model-data benchmarking; and data assimilation and ecological forecasting. This community-driven approach is key to meeting the pressing needs of science and society in the 21st century.

Pathogenic Salmonella strains have a set of virulence factors allowing them to generate systemic infections and damage in a variety of hosts. Among these factors, bacterial proteins secreted by specialized systems are used to penetrate the host’s intestinal mucosa, through the invasion and destruction of specialized epithelial M cells in the intestine. On the other hand, numerous studies have demonstrated that humans, as well as experimental animal hosts, respond to Salmonella infection by activating both innate and adaptive immune responses. Here, through live cell imaging of S. Typhimurium infection of zebrafish larvae, we showed that besides the intestinal colonization, a deformed cloacae region and a concomitant accumulation of S. Typhimurium cells was observed upon bacterial infection. The swelling led to a persistent inflammation of infected larvae, although the infection was non-lethal. The in vivo inflammation process was confirmed by the co-localization of GFP-tagged S. Typhimurium with mCherry-tagged neutrophils at 72 hours post exposition. Our live-cell analyses suggest that Salmonella Typhimurium induce cloacitis-like symptoms in zebrafish larvae. Typhimurium induce cloacitis-like symptoms in zebrafish larvae.

In graduate programs such as social work, field education is the signature pedagogy of education. As such, student placement with an appropriate field education agency is critical to ensure academic success and career readiness. A variety of Learning Management System (LMS) and Integrated Planning and Advising Service (IPAS) technologies have been developed to fully integrate technology into the educational system and streamline and improve the learning experience for students, educators, and administrators. Few (if any) of the existing solutions have capabilities to match students with field educators on the basis of an individual student’s completed coursework and area of specialization, as well as field educator needs and opportunities. This paper describes our experience developing a custom LMS/IPAS system—the School of Social Work information System (SSWiS)—that was designed specifically for student learning, faculty advising, and academic administration within our social work graduate program. We present the challenges that motivated the design of the SSWiS before describing the architecture and functionality of our solution. We then discuss our preliminary evaluation results. We conclude with a discussion of the benefits and limitations of our system in the context of today’s technical needs in graduate education in social work and other fields.

The primary aim of this study is to investigate the relationship of the Mediterranean diet (MD) with metabolic syndrome (MetS) and its components in Caucasian subjects between 35 and 74 years. The secondary aim is to analyze sex differences. Methods: A cross‑sectional trial. This study utilized data from the EVA, MARK, and EVIDENT studies, a total of 3417 subjects with a mean age of 60.14±9.14 years (57% men). MetS was defined based on the Joint Scientific Statement National Cholesterol Education Program III. Waist circumference, blood pressure, fasting plasma glucose, and lipid profile were measured. Adherence to the MD was assessed with the 14-item Mediterranean Diet Adherence Screener (MEDAS) questionnaire used in the PREDIMED study. Good adherence was considered when the MD value was higher than the median value. Results: The mean value of the MEDAS questionnaire was 5.83±2.04; (Men 5.66±2.06 and women 6.04±1.99; p&lt;0.001). Adherence to the MD was observed by 38.6% (34.3% men and 40.3% women; p&lt;0.001). MetS was observed in 41.6% (39.0% men and 45.2%women p&lt;0.001). In the multiple regression analysis after adjusting for possible confounders, the mean MD value showed a negative association with the number of MetS components per subject (β=-0.336), and with the different components of MetS: Systolic blood pressure (β=-0.011), Diastolic blood pressure (β=-0.029), glycemia (β=-0.009), Triglycerides (β=-0.004), Waist circumference (β=-0.026), except with the HDL-cholesterol value which showed a positive association (β=0.021); (p&lt;0.001 in all cases). The adjusted logistic regression models showed that an increase in MDA decreases the probability of MetS (OR =0.56) and its components: blood pressure ≥130/85 mmHg (OR = 0.63), fasting plasma glucose ≥100 mg/dL (OR = 0.62); triglycerides ≥150 mg/dL (OR = 0.65); waist circumference ≥88 cm in women and ≥102 cm in men (OR = 0.74), and increases high-density lipoprotein cholesterol &lt;40 mg/dL in men or &lt;50 mg/dL in women (OR = 1.70); (p&lt;0.001 in all cases). The results by sex were similar, both in multiple regression and logistic regression. Conclusion: The results of this study suggest that a greater adherence to the Mediterranean diet decreases the probability of presenting Mets globally and by sex.

Understanding the interplay among organophosphorus flame-retardants (OPFRs), microplastics, and freshwater organisms is crucial for unravelling the dynamics within freshwater environments and foreseeing the potential impacts of organic pollutants and plastic contamination. For that purpose, the present research assessed the exposure impact of 10 mg L–1 flame-retardant alumin-ium diethylphosphinate (ALPI), 10 μg mg–1liver microplastics polyurethane (PU), and the combina-tion of ALPI and PU on the freshwater planarian Girardia tigrina. The exposure of G. tigrina to both ALPI and PU revealed a sequential effect, i.e., a decrease in locomotor activity, while other molecular biomarkers (oxidative stress biomarkers and metabolic response) remained unaffected. Despite this fact, it was possible to observe that the range (min-max) of responses of exposed or-ganisms were altered, in the particular case of electron transport system, cholinesterase activity, glutathione S-transferase, catalase and levels of total glutathione and proteins, showing that the energetic costs for detoxification and antioxidant capacity might be causing less energy allocated for the planarian activity. By examining the physiological, behavioural, and ecological responses of planarians to these pollutants, insights can be gained into broader ecosystem-level effects and inform strategies for mitigating environmental risks associated with OPFRs and microplastic pol-lution in freshwater environments.

Management of sarcomas in specialist centers delivers significant benefits. In much of the world specialists are not available and development of expertise is identified as a major need. However the terms ‘specialist’ or ‘expert’ center are rarely defined. Our objective is to offer a definition for patient advocates and a tool for healthcare providers to underpin improving the care of people with sarcoma. SPAGN developed a discussion paper for a workshop at the SPAGN 2023 Conference, attended by 75 delegates. A presentation to the Connective Tissue Oncology Society (CTOS) and further discussion led to this paper. Core Principles were identified that underlie specialist sarcoma care. The primary principle is the multi-disciplinary team discussing every patient, at first diagnosis and during treatment. Principles for optimal sarcoma management include accurate diagnosis followed by safe, high-quality treatment, with curative intent. These Principles are supplemented by Features describing areas of healthcare, professional involvement, and service provision and identifying further research and development needs. These allow for variations because of national or local policies and budgets. We propose the term ‘Sarcoma Intelligent Specialist Network’ to recognize expertise wherever it is found in the world. This provides a base for further discussion and local refinement.

A single water pollution by dyes is a huge environmental problem; there is a necessity to produce new decolorization methods that are effective, cost-attractive, and suitable in industrial use. Magnetic chitosan polymers offer the advantage of easy separation from the dye solution. In this work, a Chitosan-Fe polymer was synthesized, characterized, and tested for removal of the azo dye Direct Red 83:1 from water. The polymer was characterized in terms of surface morphology (SEM), elemental analysis (EA), differential scanning calorimetry (DSC), thermal gravimetric analysis (TGA), infrared spectrophotometry (IR), X-ray powder diffraction (XRD) and density functional theory (DFT). The reported results hint that 1 g and pH 7.0 were the best conditions to carry out both kinetic and isotherm models. To understand the adsorption behavior of Direct Red 83:1 onto the polymers, adsorption rate and maximum adsorption capacity were calculated using kinetic tests and isotherm curves respectively. The kinetic data and mechanism of the adsorption process were analyzed by three models and the equilibrium data by three adsorption isotherms. The results indicated that the adsorption process follows a pseudo-second-order kinetics (R2= 0.999) and fits the Temkin isotherm (R2= 0.946), indicating that the adsorption occurred on heterogeneous surfaces. The newly synthesized Chitosan-Fe polymer exhibited good adsorption properties and easy separation of cleaned water.

A large diversity of epigenetic factors, such as microRNAs and histones modifications, are known to be capable of regulating gene expression without altering DNA sequence itself. In particular, miR-1 is considered the first essential microRNA in cardiac development. In this study, miR-1 potential role in early cardiac chamber differentiation is analyzed through specific signaling pathways. For this, we performed in chick embryos functional experiments by means of miR-1 microinjections into the posterior cardiac precursors -of both primitive endocardial tubes- committed to sinoatrial region fates. Subsequently, embryos were subjected to whole mount in situ hybridization, immunohistochemistry and RT-qPCR analysis. As a relevant nov-elty, our results revealed that miR-1 increases Tbx5, Gata4 and AMHC1, while this microRNA diminishes Mef2c expression, during early differentiation of cardiac sinoatrial region. Further-more, we observed in this developmental context that miR-1 upregulates CRABPII and RARß, and downregulates CRABPI, which are three crucial factors in retinoic acid signaling pathway. Interestingly, we also noticed that miR-1 directly interacts with HDAC4 and Calmodulin, as well as with Erk2/MAPK1, which are three key factors actively involved in Mef2c regulation. Our study shows, for the first time, a key role of miR-1 as an epigenetic regulator in early differenti-ation of cardiac sinoatrial region through orchestrating opposite actions between retinoic acid and Mef2c, fundamental to properly assign cardiac cells to their respective heart chambers. A better understanding of those molecular mechanisms modulated by miR-1 will definitely help in fields applied to therapy and cardiac regeneration and repair.

Verticillium wilt is a soil borne disease caused by distinct vegetative compatibility groups (VCG) of the fungus Verticillium dahliae. Two V. dahliae isolates were recovered from symptomatic cot-ton plants in Australian cotton fields and were assigned to two distinct vegetative compatibility groups (VCGs). One corresponding to the defoliating (VCG 1A) and the other non-defoliating (VCG 2A) pathotypes of Verticillium, have been transformed with Red and Green Fluorescent protein genes, respectively. The transformants maintained their ability to infect cotton and both strains were observed to colonise the xylem vessels of cotton plants. Moreover, we observed that the cotton V. dahliae strains could also infect some sampled non-Gossypium species found in the Australian landscape. The fluorescently labelled strains of V. dahliae will allow us to gain a thorough understanding of the infection processes of this important pathogen.

Crop yield estimation supported by satellite remote sensing data can provide expeditious and strategic information for farmers’ decision-making. Most recent forecasting methods have indicated a promising pathway based on machine learning algorithms. However, validation performances, demand for big data and their inherent inexplicability have not yet consolidated a substantial differential to replace methods based on simpler and more understandable models. This paper proposes an approach based on simple linear models fitted from vegetation indices (VIs) assessed at regular intervals of time series derived from MODIS satellite images, aiming to forecast cotton yields in representative areas of the Brazilian Cerrado. Data from 281 commercial production plots were taken to train (167 plots) and test (114 plots) linear regression models relating seed cotton yield and nine well-known VIs averaged in 15-days intervals. Among the evaluated VIs, EVI (Enhanced Vegetation Index) and TVI (Triangular Vegetation Index) showed the lowest root mean square errors (RMSE) and the highest determination coefficients. The best periods for in-season yield prediction were from the 90-105 to 135-150 days after sowing (DAS), i.e. phenological phases corresponding to boll development, open boll and fiber maturation, with lowest RMSE of about 750 kg ha-1 and R2=0.70. The best forecasts for early crop stages were provided by models at the peaks (maximum value of the VI time-series) for EVI and TVI, which occurred around 80-90 DAS. The proposed approach makes the yield predictability more inferable along the crop time series just by providing sowing dates, contour maps and its respective VIs.

This prospective cohort pilot study included 22 cats diagnosed with partial traumatic brachial plexus injury (PTBPI), aiming to explore the response of an early intensive neurorehabilitation protocol. This protocol included functional electrical stimulation (FES), locomotor treadmill training and kinesiotherapy exercises, starting at the time with highest probability of nerve repair. The synergetic benefits of this multimodal approach were based on the structural and protective role of proteins and release of neurotrophic factors. Furthermore, parametrization of FES was according to presence or absence of deep pain. Results have shown 72.6% (16/22) cats that achieved ambulation, with 9 cats within 15 days, 2 cats until 30 days and 5 cats until 60 days, however with persistent knuckling position. During the 4 years follow-up, there was evidence of improvement on both muscle mass and muscle weakness, in addition to the disappearance of neuropathic pain. Notably, after the 60 days of neurorehabilitation, 3 cats improved ambulation after arthrodesis of the carpus. Thus, early rehabilitation, with FES applied at the first weeks after injury and accurate parametrization according to deep pain perception, may improve functionality and ambulation, reducing probability of amputation of the affected limb.

The paper discusses the mechanism of montmorillonite structure alteration and bentonites properties modification (on the example of samples from clay deposit Taganka, Kazakhstan) due to the thermochemical treatment (treatment with inorganic acid solutions at different temperatures, concentrations and reaction times). With the use of the suit of methods certain processes were distinguished: transformation of montmorillonite structure, which appears in the leaching of interlayer and octahedral cations, protonation of the interlayer and OH groups at octahedral sheets. Changes in the structure of the 2:1 layer of montmorillonite and its interlayer result in significant changes in the properties – reduction of cation exchange capacity and an increase of specific surface area. The results of the work showed that bentonite clays retain a significant portion of its adsorption properties even after the long term and intense thermochemical treatment (6M HNO3, 60°C, 108 hours)

The synthesis of new collagen, chitosan and chitosan-collagen coated magnetic nanoparticles have been done. Two types of cross-linkers for polymer shell stabilization were used: glutaraldehyde (Gla) as a standard cross-linker and new one – squaric acid (SqA). Structure and morphology of prepared nanoparticles were characterized by ATR-FT IR, XRD and TEM analysis. The immobilization of lipase from Candida rugosa was performed on the nanoparticles surface. The amount of immobilized enzyme was quantified by the Bradford method. All of lipase-biopolymers coated nanoparticles were characterized with good activity recovery. A little hyperactivation of lipase immobilized on nanoparticles with SqA was observed. All of prepared lipase-immobilized nanoparticles were characterized with very good reusability.

Glucocorticoids (GCs) are widely used in blood cancer treatment despite their multiple adverse effects. Biological response to GCs is mediated by glucocorticoid receptor (GR) by transactivation (TA), associated with side effects, and transrepression (TR), mediating anticancer effects. Selective GR agonists (SEGRAs) preferentially activating GR TR could be better option for cancer treatment. One of well-characterized SEGRAs is 2-(4-acetoxyphenyl)-2-chloro-N-methylethylammonium-chloride (CpdA), demonstrated anticancer activity in vitro and in vivo, however its translational potential is limited due to chemical instability. CpdA derivatives CpdA-01-08 were designed by two synthetic strategies. Derivative CpdA-03 demonstrated superior GR affinity and stability compared to CpdA. Analysis of CpdA-03 ligand properties in lymphoma Granta and leukemia CEM cell lines revealed its SEGRA profile: it induced GR TR without triggering GR TA, as evidenced by changes in expression of GR target genes. Effects of CpdA-03 on cell viability, growth, and apoptosis were similar to reference GR ligand, dexamethasone (Dex), and the proto-type compound CpdA. In vivo testing of CpdA-03 anti-lymphoma activity in transplantable P388 murine lymphoma model showed that CpdA-03 reduced tumor volume threefold, outperforming Dex and CpdA. In conclusion, this work introduces CpdA-03 as promising new SEGRA with potential for further development as anti-lymphoma drug with fewer side effects.

Heterodimeric approach has emerged as a promising method for simultaneously targeting multiple receptors on tumor cells using a single molecule. Simultaneous targeting of the prostate-specific membrane antigen (PSMA) and the gastrin-releasing peptide receptor (GRPr) holds the potential to improve the accuracy of prostate cancer diagnosis. This study aimed to develop and compare six alternative routes for stereoselective synthesis of heterobivalent conjugates designed to deliver the chelating agent DOTA to PSMA/GRPr receptors. The comparison of these alternative synthetic approach, considered such factors as efficiency, complexity, synthesis and purification characteristics, as well as yields of the target compounds has been made. Optimal conditions for the stereoselective synthesis of heterobivalent ligands to PSMA and GRP, which could serve as molecular platforms for the targeted delivery of therapeutic and/or diagnostic agents to these receptors, were determined. For synthesized heterobivalent ligand 26^x and heterobivalent conjugate with DOTA 27 complete signal assignment in ¹H, ¹³C, and ¹⁵N NMR spectra was achieved using 2D NMR techniques. Based on these data, comprehensive signal assignments were provided for all final compounds in their NMR spectra.

This work addresses the challenge of EEG visual multiclass classification into 40 classes for Brain-Computer interface applications, by using deep learning architectures. The visual multiclass classification approach offers BCI applications a significant advantage, since it allows the supervision of more than one BCI interaction, considering that each class label supervises a BCI task. However, because of the nonlinearity and nonstationarity of EEG signals, performing multiclassifiers based on EEG features remains a significant challenge for BCI systems. In the present work, mutual information-based discriminant channel selection and Minimum-Norm Estimate algorithms are implemented to select discriminant channels and enhance EEG data. Hence, deep EEGNet and Convolutional-recurrent neural networks are implemented separately to classify EEG data of image visualization into 40 labels. By using the k-fold cross-validation approach, average classification accuracies of 94.8% and 89.8% were obtained by implementing the aforementioned network architectures, respectively. Satisfactory results obtained with this method offer a new implementation opportunity for multi-task BCI applications by utilizing a reduced number of channels (&lt;50%), compared to those presented in the related literature where the whole set of channels is used.

The individual and combined effects of extracellular products (ECP) from Arthrobotrys oligospora (Ao) and A. musiformis (Am) growth in liquid media against Haemonchus contortus L3 (HcL3) were assessed. The following methodological steps were established: isolation, morphological (MI) and molecular identification (Mol-I), assessment of nematocidal activity (NA) of fungal liq-uid culture filtrates (LCF) produced in two liquid media alone and in combination and finally, the myco-compound profile identification (MCP). The MI of both isolates suggested that the fungi corresponded to the species Ao and Am. This result was confirmed by PCR analysis followed by sequencing, alignment and obtaining coverage and similarity with respect to isolates reported in the NCBI database. Likewise, the highest Hc mortalities were 91.4% with individual LCF of Am and 86.2% with those of Ao at the highest concentration (100 mg/mL) in Czapek-Dox Broth. The combination of both LCF resulted in a similarly high larval mortality with no statistical differ-ences in relation to individual activity (P>0.05). The MCP showed the presence of alkaloids in both fungi. Coumarins, triterpenes and saponins were found only in Ao. Both fungi produced ECP with a high NA that could be identified and assessed in future studies as potential natural an-thelmintic compounds.

To assess if SARS-CoV-2 infection induces changes in the urinary volatilomic fingerprint able to be used in the non-invasive COVID-19 diagnosis and management, urine samples of SARS-CoV-2 infected patients (62), recovered COVID-19 patients (30), and non-infected individuals (41) were analysed using solid-phase microextraction technique in headspace mode, combined with gas chromatography hyphenated with mass spectrometry (HS-SPME/GC-MS). In total, 101 volatile organic metabolites (VOMs) from 13 chemical families were identified, being terpenes, phenolic compounds, norisoprenoids, and ketones the most represented groups. Overall, a decrease in the levels of terpenes and phenolic compounds was observed in the control group, whereas norisoprenoids and ketones showed a significant increase. In turn, a remarkable increase was noticed in norisoprenoids and ketones and a milder increase in alcohols, furanic, and sulfur compounds in the recovery group than in the COVID-19 group. Multivariate statistical analysis identified sets of VOMs with the potential to constitute volatile signatures for COVID-19 development and progression. These signatures are composed of D-carvone, 3-methoxy-5-(trifluoromethyl)aniline (MTA), 1,1,6-trimethyl-dihydronaphthalene (TDN), 2-heptanone, and 2,5,5,8a-tetramethyl-1,2,3,5,6,7,8,8-octahydro-1-naphthalenyl ester acetate (TONEA) for COVID-19 infection and nonanoic acid, α-terpinene, β-damascenone, α-isophorone, and trans-furan linalool for patients recovering from the disease. This study provides evidence that changes in the urinary volatilomic profile triggered by SARS-CoV-2 infection constitute a promising and valuable screening and/or diagnostic and management tool for COVID-19 in clinical environment.

Nowadays, the growing concern about improving thermal comfort in textiles, asphalt pavements and buildings has stimulated research into phase change materials (PCMs). However, the incorporation of PCMs directly causes mechanical impacts. Therefore, this study herein reported focuses on designing coaxial phase change fibres using commercial cellulose acetate (CA) or recycled CA obtained from cotton fabrics (CAt) as a coating and polyethylene glycol (PEG) 2000 as a core. The phase change fibres (PCF) were produced by wet spinning, varying the parameters: (i) CA concentration, molecular weight and source (virgin versus recycled); and (ii) PEG concentration and ejection. For phase change recycled fibres (PCFt), PEG concentration and ejection were varied. The fibres were assessed for their optical, chemical, thermal and mechanical properties. Bright-field microscopy images and Scanning Electron Microscopy (SEM) micrographs proved the coaxial structure. Fourier Transform Infrared spectroscopy (FTIR) confirmed the presence of PEG in the core. Thermogravimetric Analysis (TGA) proved the ability of PCFs to tolerate high temperatures. Differential Scanning Calorimetry (DSC) attested to the presence of PEG2000 peaks, since their melting points were close to those of virgin PEG2000, with a slight change in the PCFs and PCFts caused by the protective sheath of CA and CAt.

The repurposing of licenced drugs for use against COVID-19 is one of the most rapid ways to develop new and alternative therapeutic options to manage the ongoing pandemic. Given the approximately 8,000 licenced compounds available from Compounds Australia that can be screened, this paper demonstrates the utility of commercially-available ex vivo/3D airway and alveolar tissue models. These models are a closer representation of in vivo studies compared to in vitro models, but retain the benefits of rapid in vitro screening for drug efficacy. We demonstrate that several existing drugs appear to show anti-SARS-CoV-2 activity against both Delta and Omicron Variants of Concern in the airway model. In particular, fluvoxamine, as well as aprepitant, everolimus, and sirolimus have virus reduction efficacy comparable to the current standard of care (remdesivir, molnupiravir, nirmatrelvir). Whilst these results are encouraging, further testing and efficacy studies are required before clinical use can be considered.

While the scientific community has focused on documenting environmental degradation and developing scenarios that help identify the operational margins for system Earth, less attention has been given to the mental models of decision-makers that underpin environmental policies. We suggest that global efforts to stop deforestation and biodiversity loss are failing in part due to a critical blind spot in the analysis—human agency. To address this weakness, we propose to formulate mental models and translate them into strategy games. This will increase the representation of agency in scenario development and create spaces for deliberation between different worldviews. We claim that personal transformation can be achieved through transparent democratic dialogues that identify, challenge, and respond to the human and social limitations inherent to decision-making and we present empirical examples that validate that claim. Their transformation through gaming gives decision-makers access to the experience of consciousness: “what is it like being a stakeholder?”. Such experience will help to break free of established norms in science and political processes.

Viral infections leading to inflammation have been implicated in several common diseases such as Alzheimer’s disease (AD) and type 1 diabetes (T1D). Of note, herpes simplex virus 1 (HSV-1) has been reported to be associated with AD. We sought to identify the transcriptomic changes due to HSV-1 infection and anti-viral drug (acyclovir, ACV) treatment of HSV-1 infection in dissoci-ated cells from human cerebral organoids (dcOrgs) versus stem cell-derived pancreatic islets (sc-islets) to gain potential biological insights into the relevance of HSV-1-induced inflammation in AD and T1D. We observed that differentially expressed genes (DEGs) in HSV-1-infected sc-islets were enriched for genes associated with several autoimmune diseases, most significantly T1D but also rheumatoid arthritis, psoriasis, Crohn’s disease, and multiple sclerosis, whereas DEGs in HSV-1-infected dcOrgs were exclusively enriched for genes associated with AD. ACV treatment of sc-islets did not rescue transcript expression of autoimmune disease-associated genes. Finally, we identified gene ontology categories that were enriched for DEGs that were in common across, or unique to, viral treatment of dcOrgs and sc-islets, such as categories involved in the transferase complex, mitochondrial and autophagy function. Collectively, this studies pro-vide insight to the molecular effects of inflammation in AD and T1D.

. Background. Hypoxic-ischemic brain injury is one primary cause of long-term neurological disability, morbidity, and death worldwide. The decrease in blood flow and oxygen concentration leads to insufficient nutrient supply to the brain, energy depletion, increased free radical generation, and mitochondrial dysfunction. Perinatal asphyxia — the oxygen supply suspension near birth-time — causes hypoxic-ischemic brain injury and is a major risk factor for neurodevelopmental damage. In pathological scenarios, raloxifene, a selective estrogen receptor modulator, has shown neuroprotective effects. Purpose. To examine whether raloxifene showed neuroprotection in an oxygen-glucose deprivation/reoxygenation astrocyte cell model. Methods. T98G cells in culture were treated with a glucose-free DMEM medium and incubated at 37ºC in a hypoxia chamber with 1% O2 for 3, 6, 12, and 24 hours. Cultures were supplemented with raloxifene 1, 10, and 100 nM during both glucose and oxygen deprivation and reoxygenation periods. Results. Raloxifene 100 nM and 10 nM improved cell survival — 65.34% and 70.56% — respectively compared to the control cell groups. Mitochondrial membrane potential was preserved by 58.9% 10 nM raloxifene and 81.57% 100 nM raloxifene cotreatment. Raloxifene cotreatment reduced superoxide production by 72.72% and peroxide production by 57%. Mitochondrial mass was preserved by 47.4%, 75.5%, and 89% in T98G cells exposed to 6-hour oxygen-glucose deprivation followed by 3, 6, and 9 hours of reoxygenation, respectively. Conclusions. Raloxifene improved cell survival and mitochondrial membrane potential, and reduced lipid peroxidation and reactive oxygen species (ROS) production, suggesting a direct effect on mitochondria. Raloxifene protected the oxygen-glucose-deprived astrocyte cells used to mimic hypoxic-ischemic brain injury in this study.

In virology, the term reverse genetics refers to a set of methodologies in which changes are introduced into the viral genome and their effects on the generation of infectious viral progeny and their phenotypic features are assessed. Reverse genetics emerged thanks to advances in recombinant DNA technology, which made the isolation, cloning, and modification of genes through mutagenesis possible. Most virus reverse genetics studies depend on our capacity to rescue an infectious wild-type virus progeny from cell cultures transfected with an “infectious clone”. This infectious clone generally consists of a circular DNA plasmid containing a functional copy of the full-length viral genome, under the control of an appropriate polymerase promoter. For most DNA viruses, reverse genetics systems are very straightforward, since DNA virus genomes are relatively easy to handle and modify and are also (with few notable exceptions) infectious per se. This is not true for RNA viruses, whose genomes need to be reverse transcribed into cDNA before any modification can be done. Establishing reverse genetics systems for members of the Caliciviridae has proven exceptionally challenging, due to the low number of members of this family that propagate in cell culture. Despite the early successful rescue of a calicivirus from a genome-length cDNA more than two decades ago, reverse genetics methods are not routine procedures that can be easily extrapolated to other members of the family. Reports of calicivirus reverse genetics systems have been few and far between. In this review, we discuss the main pitfalls, failures, and delays behind the generation of several successful calicivirus infectious clones.

Background: Radiotherapy in the head-and-neck area is one of the main curative treatment options. However, this comes at the cost of varying levels of normal tissue toxicity, affecting up to 80% of patients. Mucositis can cause pain, weight loss and treatment delay leading to worse outcomes and decreased quality of life. Therefore, there is an urgent need for an approach to predict normal mucosa response in patients prior to treatment. Methods: We here describe an assay to detect irradiation response in patient healthy oral mucosa tissue. Mucosa specimens from the oral cavity were obtained after surgical resection, cut into thin slices, irradiated, and cultured for three days. Seven samples were irradiated with X-ray and three additional samples were irradiated with both X-ray and protons. Results: Healthy oral mucosa tissue slices maintained normal morphology and viability for three days. We measured a dose-dependent response to X-ray irradiation and compared X-ray and proton irradiation in the same mucosa sample, using standardized automated image analysis. Furthermore, increased levels of inflammation inducing factors - major drivers in mucositis development - could be detected after irradiation. Conclusion: This model can be utilized for investigating mechanistic aspects of mucositis development and can be developed into an assay to predict radiation-induced toxicity in normal mucosa.

The Herpotrichiellaceae family is an important group of dematiaceous filamentous fungi, associated with a variety of pathogenic fungal species causing Chromoblastomycosis (CBM) and Phaeohyphomycosis (PHM), both with polymorphic clinical manifestations and worldwide incidence. Currently, the identification of this family and determination of the causative agent is challenging due to the subjectivity of morphological identification methods, necessitating the use of molecular techniques to complement diagnosis. In this context, genetic sequencing of the Internal Transcribed Spacer (ITS) has become the norm due to a lack of alternative molecular tools for identifying these agents. Therefore, this study aimed to develop PCR-Multiplex methodologies to address this gap. Sequences from the ITS and Large subunit (LSU) of ribosomal DNA were used, and after manual curation and in vitro analyses, primers were synthesized for the identification of the aforementioned targets. The primers were optimized and validated in vitro, resulting in two PCR-Multiplex methodologies: one for identifying the Herpotrichiellaceae family and the bantiana clade, and another for determining the species Fonsecaea pedrosoi and Fonsecaea monophora. Ultimately, the assays developed in this study aim to complement other identification approaches for these agents, reducing the need for sequencing, improving the management of these infections, and enhancing the accuracy of epidemiological information.

In this review, we outline our current understanding of the mechanisms involved in the absorption, storage, and transport of dietary vitamin A to the eye, the trafficking of rod opsin protein to the photoreceptor outer segments, which encompasses the logistical backbone required for visual function. Two key mechanisms of this process are emphasized in this manuscript: Ocular and systemic vitamin A membrane transporters, and rhodopsin transporters. Understanding the complementary mechanisms responsible for the generation and proper transport of the retinylidene opsin to the photoreceptor outer segment will eventually shed light on the importance of genes encoded by these proteins, and their relationship on normal visual function and in the pathophysiology of retinal degenerative diseases.

Introduction: In recent years, generative Artificial Intelligence models, such as ChatGPT, have been increasingly utilized in healthcare. Despite acknowledging the high potential of AI models in terms of quick access to sources and formulating a response to a clinical question, the results obtained using these models still require validation through comparison with established clinical guidelines. This study compares the responses of the AI model to eight clinical questions with the Italian Association of Medical Oncology (AIOM) guidelines for ovarian cancer. Materials and Methods: The authors used the Delphi method to evaluate responses from ChatGPT and the AIOM guidelines. An expert panel of healthcare professionals assessed responses based on clarity, consistency, comprehensiveness, usability, and quality using a 5-point Likert scale. The GRADE methodology assessed the evidence quality and the recommendations' strength. Results: A survey involving 14 physicians revealed that the AIOM guidelines consistently scored higher averages compared to the AI models with a statistically significant difference. Post-hoc tests showed that AIOM guidelines significantly differed from all AI models, with no significant difference among the AI models. Conclusions: While AI models can provide rapid responses, they must match established clinical guidelines regarding clarity, consistency, comprehensiveness, usability, and quality. These findings underscore the importance of relying on expert-developed guidelines in clinical decision-making and highlight potential areas for AI model improvement.

Probiotics are microorganisms infused in products for health benefits including acceleration of nutrient digestion, however, it is also important to ensure the safety prior to incorporation. Here, we present evidence of the ability of two probiotic isolates,Lacticaseibacillus paracasei BCRC-16100 and Lacticaseibacillus paracasei ZFM54, in the (1) enhancement of carbohydrate digestion, (2) tolerance to stress, and (3) antibiotic resistance. Approaches include whole genome sequence (WGS) analysis and bioactivity assays. WGS revealed genes suggesting the ability of the two isolates to promote carbohydrate digestion, tolerance to stress and antibiotic resistance. Carbohydrate digestive ability was confirmed through a biochemical assay where the two isolates cause glucose release from starch. The two isolates also showed versatility in a range of temperature and alcohol concentration. For antibiotic resistance particularly on vancomycin, there are three mechanisms namely transporter control, transcriptional regulation, and efflux pump. Furthermore, promoter and transposable element analysis showed that some of the active antibiotic resistant (AbR) genes can be laterally transferred. Altogether, we show the potential of two probiotic isolates to be incorporated in products for improved carbohydrate digestion and the need to address the removal of active and mobile antibiotic resistance genes that may compromise safety.

Histone changes that are adjustable and transmitted without altering the DNA sequence are part of epigenetic control. In many disorders, most famously malignancy, abnormal genetic information is seen as a result of mismanagement of typical epigenetic mechanisms. A paradigm change in the diagnosis and treatment of cancer has been brought about by recent discoveries about the processes of epigenetic modifications, chromatin remodeling, and noncoding RNAs implicated in the changed expression patterns of tumor cells. There is a significant increase in the search for drugs that could alter the epigenetic environment altered by tumor cells and benefit from their therapeutic potential. Phytochemicals with a high concentration of naturally produced phenol molecules known as flavonoids can regulate genomic processes. Understanding the precise epigenetic alterations brought on by flavonoid-mediated mechanisms is necessary to develop combination therapy techniques and genomic therapies for cancer. This article aims to thoroughly examine the epigenetic modifications of flavonoids, including their anticancer properties.

(1) Background: Breast cancer is the leading malignancy worldwide and in Ghana it has a poor overall survival. However, approximately 50% of cases are early stage disease and with advances in breast cancer treatment and improvement in survival, quality of life (QOL) becomes as im-portant as treatment of the disease. (2) Methodology: This was a cross-sectional study of survivors who had breast conserving surgery (BCS), mastectomy only (M) and mastectomy with breast re-construction (BRS) from 2016 to 2020 at a tertiary hospital in Ghana, comparatively assessing their QOL using EORTC QLQ C-30 and EORTC QLQ BR-23. (3) Results: The study participants had an overall Global Health Status (GHS) median score of 83.3 [IQR: 66.7-91.7] with no significant differences between the surgery types. The BRS group had a statistically significant lower median scores for the Functional scale (82.8 and 51.0) and the highest scores for the Symptomatic scale (15.7 and 16.5). Body image was significantly lowest for the BRS group 83.3 [68.8-91.7] and highest 100 [91.7-100] for the BCS group (p < 0.001). (4) Conclusion: There is a need to develop support systems tailored at improving the QOL of breast cancer survivors taking into consideration the type of surgery performed.

All types of sports are potential application scenarios for automatic and real-time visual object and event detection. In rink hockey, the popular roller quad skate variant of hockey team sports, it is of great interest to automatically track player’s movements and positions, player’s sticks and, also, making other judgments, such as being able to locate the ball. In this work, we introduce a real-time pipeline composed by an object detection model, created specifically for rink hockey games, followed by a knowledge-based event detection module. Even in the presence of occlusions and quick motions, our deep learning object detection model effectively identifies and tracks, in real-time, important visual elements such as: ball; players; sticks; referees; crowd; goalkeeper; and goal. Using a curated dataset composed by a collection of videos of rink hockey, comprising 2525 annotated frames, we trained and evaluated the algorithm performance and compare it to state of the art object detection techniques. Our object detection model, based on YOLOv7, presents a global accuracy of 80%, and presents a good performance in terms of accuracy and speed, according to our results, making it a good choice for rink hockey applications. In our initial tests, the event detection module successfully detected one important event type in rink hockey games, the occurrence of penalties.

Dipeptidyl peptidase 9 (DPP9) is a multifunctional intracellular protease with roles in tumour growth, inflammation and mitochondrial function. We developed a hepatocyte-specific DPP9 knockout mouse (DPP9-KO) to explore DPP9 in a mouse model of hepatocellular carcinoma (HCC). DPP9-KO mice were generated by crossing Albumin-Cre mice (Wt/Wt Cre+/+) with DPP9 floxed mice (Fl/Fl Cre-/-). Mice were treated with Diethylnitrosamine and Thioacetamide then an atherogenic High Fat Diet until 28 weeks of age. DPP9-KO mice had reduced liver and subcuta-neous adipose tissue mass and lower fasting plasma glucose, fewer small macroscopic liver nod-ules compared to DPP9-WT mice. However, there were no differences in the total number of mac-roscopic liver nodules, tumour burden, inflammation score and steatosis score. Consistent with the known ability of DPP9 to suppress NLRP1 activation, activated caspase-1 protein was ele-vated in DPP9-KO mouse liver. Additionally, Nfkbib, Cxcl10 and Ccl5 mRNA and protein levels of autophagy marker beclin1 and tumour suppressor p53 were increased. In conclusion, DPP9 de-pletion in hepatocytes may reduce liver cancer initiation, via mechanisms that may include in-creased autophagy and innate tumour suppression in this experimental model. Finally, the data supports DPP9 having a role in glucose regulation by the liver.

The COVID-19 pandemic is the biggest public health threat facing the globe today. Multiple vaccines have been approved, however the emergence of viral variants such as the recent Omicron, raises the possibility of booster doses to achieve adequate protection. In Brazil, the CoronaVac (Sinovac) vaccine was used, however it’s important to assess the immune response to this vaccine over time. This study aimed to monitor the anti-SARS-CoV-2 antibody responses in those immunized with CoronaVac and SARS-CoV-2 infected individuals. Samples were collected between August 2020 and August 2021. Within the vaccinated cohort, some individuals had history of infection by SARS-CoV-2 prior to immunization and others not. We analyzed RBD-specific and neutralizing- antibodies. Anti-RBD antibodies were detected in both cohorts, with a peak between 45-90 days post infection or vaccination, followed by a steady decline over time. In those with previous history of COVID-19, a higher, longer, more persistent response was observed. This trend was mirrored in the neutralization assays, where infection followed by immunization resulted in higher, longer lasting responses which were conditioned on the presence of levels of RBD antibodies right before the vaccination. This supports the necessity of booster doses of CoronaVac in due course to prevent serious disease.

The objective of this study was to evaluate the efficacy of one-step nucleic acid amplification (OSNA) for the detection of sentinel lymph node (SLN) metastasis compared to standard pathological ultrastaging in patients with early-stage endometrial cancer (EC). A total of 526 SLNs from 191 patients with EC were included in the study. 379 SLNs (147 patients) were evaluated by both methods, OSNA and standard pathological ultrastaging. The central 1-mm portion of each lymph node was subjected to semi-serial sectioning at 200-μm intervals and examined by hematoxylin-eosin and immunohistochemistry with CK19; the remaining tissue was analysed by OSNA for CK19 mRNA. The OSNA assay detected metastases in 19.7% of patients (14.9% micrometastasis and 4.8% macrometastasis), whereas pathological ultrastaging detected metastasis in 8.8% of patients (3.4% micrometastasis and 5.4% macrometastasis). Using the established cut-off value for detecting SLN metastasis by OSNA in EC (250 copies/μl), the sensitivity of the OSNA assay was 92%; specificity was 82%; diagnostic accuracy was 83%, and the negative predictive value was 99%. Discordant results between both methods were recorded in 20 patients (13.6%). OSNA resulted in an upstaging in 12 patients (8.2%). OSNA could aid in the identification of patients requiring adjuvant treatment at the time of diagnosis.

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.

Purpose: Investigation for the co-occurrence of two unrelated genetic disorders of muscular dystrophy and Prader-Willi syndrome (PWS) (OMIM # 176270) using joint whole genome sequencing (WGS). Methods: Trio WGS joint analysis was performed to investigate the genetic etiology in a proband with PWS, prolonged muscular hypotonia associated hyperCKemia, and early-onset obesity. The parents were unaffected. Results: Results showed maternal isodisomy uniparental disomy (UPD) in chromosome 15 expanding from 15q11.2 to 15q22.2, including PWS regions at 15q11.2-15q13. Maternal heterodisomy was detected from 15q22.2 to 15q26.3. A pathogenic variant, NM_000070.3(CAPN3):c.550del (p.Thr184fs), was identified at 15q15.1 in a heterozygous state in the mother that was homozygous in the proband due to maternal isodisomy. Conclusion: This is the first study of the concurrent molecular etiology of PWS and calpainopathy (OMIM # 253600) in the same patient. This report highlights the utility of joint analysis and need for the assessment of autosomal recessive disease in regions of isodisomy in patients with complex and unexplained phenotype.

There are several challenges on how to attain energy efficiency while maintaining balance among factors affecting energy consumption such as power rating and temperature setpoints of cooling units, room temperature and humidity, and indoor air quality (IAQ). A real-time energy and IAQ monitoring system were installed in an educational building to profile the operational power consumption of inverter-based air condition unit (ACU) installed in each room. Polynomial curve and neural fitting regression analysis were applied to the real-time power consumption, indoor temperature and humidity, and carbon dioxide (CO2) level data. The derived models were able to provide the stabilizing indoor thermal and air conditions of the room to reach steady state ACU power consumption. These collected data and calculated parameters can be used to define rules in automating control of cooling appliances for an efficient energy utilization. The regression approaches, using real-time data, have determined the influence of indoor heat conditions and carbon dioxide levels on ACU power consumption. These parameters were utilized to establish consistent values for temperature, humidity, and carbon dioxide levels under stable settings of inverter-based air conditioning units.

Background: Primary cardiac sarcomas (PCS) are extremely rare malignant tumors involving the heart. Only isolated case reports have been described. There is a paucity of data on the epidemiological characteristics of PCS. This study has the objective of investigating the epidemiologic characteristics, survival outcomes, and independent prognostic factors of PCS. Methods: We enrolled a total of 362 patients with PCS, between 2000 and 2017, by retrieving the Surveillance, Epidemiology, and End Results (SEER) database. We analyzed demographics, clinical characteristics, and overall mortality (OM) as well as cancer-specific mortality (CSM) of PCS. Variables with a p-value < 0.1 in the univariate Cox regression were incorporated into the multivariate Cox model to determine the independent prognostic factors, with a hazard ratio (HR) of greater than 1 representing adverse prognostic factors. Results: Crude analysis revealed a high OM in age 80+ (HR=5.958, 95% CI 3.357-10.575, p=0), followed by age 60-79 (HR=1.429, 95% CI 1.028-1.986, p=0.033); and PCS with distant metastases (HR=1.888, 95% CI 1.389-2.566, p=0). Patients that underwent surgical resection of the primary tumor and patients with malignant fibrous histiocytomas (HR=0.657, 95% CI 0.455-0.95, p=0.025) had a better OM (HR=0.606, 95% CI 0.465-0.791, p=0). The highest cancer-specific mortality was observed in age 80+ (HR=5.037, 95% CI 2.606-9.736, p=0) and patients with distant metastases (HR=1.953, 95% CI 1.396-2.733, p=0). Patients with malignant fibrous histiocytomas (HR=0.572, 95% CI 0.378-0.865, p=0.008) and those who underwent surgery (HR=0.581, 95% CI 0.436-0.774, p=0) had a lower CSM. Multivariate Cox proportional hazard regression analyses revealed higher OM in the age group 80+ (HR=13.261, 95% CI 5.839-30.119, p=0) and advanced disease with distant metastases (HR=2.013, 95% CI 1.355-2.99, p=0.001). Lower OM was found in patients with rhabdomyosarcoma (HR=0.364, 95% CI 0.154-0.86, p=0.021) and widowed patients (HR=0.506, 95% CI 0.263-0.977, p=0.042). Multivariate Cox proportional hazard regression analyses of CSM also revealed higher mortality in the same groups, and lower mortality in patients with Rhabdomyosarcoma. Conclusion: In this United States population-based retrospective cohort study using the SEER database, we found that cardiac rhabdomyosarcoma was associated with the lowest CSM and OM. Furthermore, as expected, age and advanced disease at diagnosis were independent factors predicting poor prognosis. Surgical resection of the primary tumor showed lower CSM and OM in the crude analysis but when adjusted for covariates in the multivariate analysis, it did not significantly impact the overall mortality or the cancer-specific mortality. These findings allow for treating clinicians to recognize patients that should be referred to palliative/hospice care at the time of diagnosis and avoid any surgical interventions as they did not show any differences in mortality. Surgical resection in patients with poor prognoses should be reserved as a palliative measure rather than an attempt to cure the disease.

Fructose consumption has been growing exponentially and, concomitant with this, the increase in the incidence of obesity and associated complications has followed the same behavior. Studies indicate that fructose may be a carbohydrate with greater obesogenic potential than other sugars. In this context, the liver seems to be a key organ for understanding the deleterious health effects promoted by fructose consumption. Fructose promotes complications in glucose metabolism, accumulation of triacylglycerol in the hepatocytes and alterations in the lipid profile, which, associated with an inflammatory response and alterations in the redox state, will imply a systemic picture of insulin resistance. However, physical exercise has been indicated for the treatment of several chronic diseases. In this review, we show how each exercise protocol (aerobic, strength or a combination of both) promote improvements in the obesogenic state created by fructose consumption as an improvement in the serum and liver lipid profile (HDL increase and decrease TG and LDL levels) and a reduction of markers of inflammation caused by an excess of fructose. Therefore, it is concluded that the practice of aerobic physical exercise, strength or a combination of both is essential for attenuating the complications developed by the consumption of fructose.

Neoadjuvant therapy (NAT) for early-stage pancreatic ductal adenocarcinoma (PDA) has recently gained prominence. We investigated the clinical significance of mucin 5 AC (MUC5AC), which exists in two major glycoforms, a less-glycosylated immature isoform (IM) and a heavi-ly-glycosylated mature isoform (MM), as a biomarker in resected PDA. Immunohistochemistry was performed on 100 resected PDAs to evaluate the expression of IM and MM isoforms of MUC5AC using respective monoclonal antibodies CLH2 (NBP2-44455) and 45M1 (ab3649). MUC5AC localization (cytoplasmic, apical, and extra-cellular, EC) was determined, and H-scores were calculated. Univariate and multivariate (MVA) Cox regression models were used to estimate progression-free survival (PFS) and overall survival (OS). Of 100 resected PDA patients, 43 received NAT, and 57 were treatment-naïve with upfront surgery (UpS). In the study population (N=100), IM expression (objective response vs. no response vs. UpS = H-scores 104 vs. 152 vs. 163, p=0.01) and MM-MUC5AC detection rates (56% vs. 63% vs. 82%, p=0.02) were significantly different. In the NAT-group, MM-MUC5AC-negative patients had significantly better PFS on MVA (Hazard Ratio, 0.2, 95 % CI: 0.059-0.766, p = 0.01). Similar results were noted in a FOLFIRINOX sub-group (N=36). We established an association of MUC5AC expression with treatment response and outcomes.

The ACEtabular rim eXtension (ACE-X) implant is a custom-made 3-dimensional-printed titanium device designed for the treatment of canine hip dysplasia. Thirty-four dogs (61 hips) underwent ACE-X implantation, and assessments were conducted using computed tomography, force plate analysis, Ortolani’s test, and Helsinki Chronic Pain Index (HCPI) questionnaires at five intervals: pre-operative day, surgery day, 1.5-month, 3-month, and 12-month follow-up. Statistically significant increases in femoral head coverage with negative Ortolani subluxation test were observed immediately after surgery and persisted throughout the study. Osteoarthritis (OA) scores remained stable, but osteophyte size significantly increased between the surgery day and the 12-month follow-up, especially in hips with a baseline OA score of 2 compared to those with a score of 1. Force plate data showed no significant changes during the study. The HCPI demonstrated a significant decrease in pain score from pre-operative value to 6-week follow-up and gradually decreased over time. Major complications were identified in 6 hips (9.8%) of 4 dogs. In conclusion, the ACE-X implant effectively increased femoral head coverage, eliminated subluxation, and provided long-term pain relief with minimal complications, benefiting over 90% of the study population. The study supports the ACE-X implant as a secure and valuable treatment for canine hip dysplasia.

Invasive fungal disease causes high morbidity and mortality among immunocompromised patients. Anti-fungal drug resistance and cytotoxicity highlight the need for effective antifungal therapeutics. In this study, the antifungal potential of the ethanolic extract of Anacardium occidentale (Cashew Leaf) leaves were evaluated against Candida albicans and C. auris. The antifungal activity was tested by the broth microdilution method and growth kinetic test. To further explore its antifungal action mode, spectrofluorophotometry, confocal microscopy and scanning and transmission electron microscopy were performed, Additionally, heterozygous knockout strains associated with resistance to oxidative stress were included in the study. We found that A. occidentale could inhibit the proliferation and growth of C. albicans at concentrations of 62.5 and 125 μg/mL. the doubling time was also drastically affected, going from 2.8 hours to 22.5 hours. Which was also observed in C. auris. The extract induced the accumulation of intracellular reactive oxygen species (ROS), resulting in endoplasmic reticulum stress and mitochondrial dysfunction, while it did not show cy-totoxicity or hemolytic activity at the concentrations evaluated. Our work preliminarily elucidated the po-tential mechanisms of A. occidentale against C. albicans on a cellular level and might provide a promising op-tion for the design of a new treatment for invasive candidiasis

The objective of this study was to determine how application with dolomitic limestone and grazing type (continuous or deferred) affect sheep grazing location and feed preference when the pasture growth rate is maximum. A 4ha field was divided into 4 plots: P1 and P2- without application of dolomitic limestone, continuous (CG) and deferred grazing (DG), respectively; P3 and P4- with application of dolomitic limestone, DG (1AUE), and CG (2.4 AUE), respectively. In DG, animals were placed and removed from the plots depending on the height of the pasture. In each plot, 12 georeferenced sampling points were identified. Throughout the pasture's vegetative cycle (autumn, winter, spring, and early summer) several measurements of pasture height and cut were carried out. From the beginning of March to the beginning of June, animal behavior was observed, by trained observers, through binoculars on six dates. Animals' activity grazing and location was recorded. The results show that: (i) the application of dolomitic limestone combined with CG provided higher values of pasture height; (ii) there were no significant differences in pasture quality between treatments; (iii) Deferred grazing led to 50% more sheep grazing days than continuous grazing; (iv) there were no significant differences in soil compaction between CG and DG; (v) the type of grazing and the treatment with dolomitic limestone did not seem to change the grazing pattern between treatments. This work contributes to understanding the relationships between different types of grazing in dryland pastures, with and without application of dolomitic limestone, and preferred grazing locations for sheep. This work could help agricultural managers make more informed decisions with the aim of promoting the sustainable intensification of livestock production in the Montado ecosystem.

Familial Mediterranean fever (FMF) is a systemic autoinflammatory disorder caused by inherited mutations in the MEFV (Mediterranean FeVer) gene located on chromosome 16 (16p13.3) and coding pyrin protein. Despite the existing data on MEFV mutations, the exact mechanism of their effect on the development of pathological processes leading to autoinflammation observed in FMF, remains unclear. Induced pluripotent stem cells (iPSCs) are considered an important tool for studying the molecular genetic mechanisms of various diseases due to their ability to differentiate into any cell type, including macrophages, which contribute to the development of FMF. In this study, we developed iPSCs of an Armenian patient with FMF having M694V, p.(Met694Val) (c.2080A&gt;G, rs61752717) pathogenic mutation in exon 10 of the MEFV gene. As a result of direct differentiation, macrophages expressing CD14 and CD45 surface markers were obtained. In addition, we found that the morphology of patient macrophages derived from iPSCs with MEFV mutation was significantly different from that of differentiated from iPSCs of a healthy donor carrying wild-type MEFV gene.

Background: Large-cell neuroendocrine carcinoma presents significant treatment challenges owing to its rarity and limited therapeutic options. The LANCE study was designed to explore the survival benefits of incorporating atezolizumab in chemotherapy for metastatic LCNEC. Methods: In this non-randomized study, patients with metastatic LCNEC were treated with ei-ther standard chemotherapy plus atezolizumab or standard chemotherapy alone. The primary outcomes measured were progression-free survival (PFS) and overall survival (OS), with an ex-ploratory analysis of miR375 in plasma as a potential biomarker. Results: Of the 22 screened patients, 17 met the inclusion criteria and were stratified into the atezolizumab and chemotherapy (n=10) or chemotherapy alone(n=7) groups. After a median follow-up of 23.3 months, the 12-month survival rate for the atezolizumab group was 57.1% (95% CI: 32.6%-100%) and 45.7% at 24 months (95% CI: 22.4%-93.2%). In contrast, the chemotherapy group had a 14.3% survival rate at both 12 and 24 months (95% CI: 2.33%-87.7%). The log-rank test for survival showed a statistically significant difference in the atezolizumab-treated group (chi-squared = 4, df = 1, p = 0.04). A non-significant correlation was found between disease pro-gression and elevated levels of miR375. Conclusions: This pilot study suggests that atezolizumab combined with chemotherapy may be effective in treating metastatic LCNEC. The non-significant correlation between plasma miR375 levels and disease progression suggests its biomarker potential, warranting further validation research.

Infection with human immunodeficiency virus (HIV) and induced acquired immune deficiency syndrome (AIDS) represent one of the greatest health burdens worldwide. The complex pathophysiological pathways that link highly active antiretroviral therapy (HAART) and HIV infection per se with dyslipidemia make the management of lipid disorders and the subsequent increase in cardiovascular risk essential for the treatment of people living with HIV (PLHIV). Amongst the HAART regimens, darunavir and atazanavir in terms of protease inhibitors, tenofovir disoproxil fumarate, nevirapine or rilpivirine in terms of nucleoside reverse transcriptase inhibitors and non-nucleoside reverse transcriptase inhibitors respectively, and especially integrase inhibitors, have demonstrated the most favorable lipid profile emerging as sustainable options in HAART substitution. To this day, statins remain the cornerstone pharmacotherapy for dyslipidemia in PLHIV, although important drug-drug interactions with different HAART agents should be taken into account upon treatment initiation. For those intolerant or not meeting therapeutic goals, the addition of ezetimibe, PCSK9, bempedoic acid, fibrates or fish oils should also be considered. This review summarizes the current literature on the multifactorial etiology and intricate pathophysiology of hyperlipidemia in PLHIV, with an emphasis on the role of different HAART agents, while also providing valuable insights into potential switching strategies and therapeutic options.

Traumatic nerve injuries are common lesions that affect several hundred thousand humans, as well as dogs and cats. The assessment of nerve regeneration trough animal models may provide information for translational research and future therapeutic options that can be applied mutually in veterinary and human medicine, in a one health perspective. This review offers a hands-on vision about the non-invasive and conservative approaches on peripheral nerve injury, focusing the role of neurorehabilitation in nerve repair and regeneration. The peripheral nerve injury may lead to hypersensitivity, allodynia and hyperalgesia, with the possibility of joint contractures, decreasing functionality and impairing the quality of life. The question remains regarding how to improve nerve repair with surgical possibilities, but also considering electrical stimulation modalities by modulating sensory feedback, upregulation BDNF, GFNF, TrKB and adenosine monophosphate, maintaining muscle mass and modulating fatigue. This could be improved by the positive synergetic effect of exercises and physical activity with locomotor training, and other physical modalities, such as low-level laser therapy and ultrasounds. In addition, the use of cell-based therapies is an innovative treatment tool in this field. These strategies may help avoiding situations of permanent monoplegic limbs that could lead to amputation.

Cardiomyopathies are major causes of heart failure. Chagas disease (CD) is caused by the parasite Trypanosoma cruzi, and it is endemic in Central, South America. Thirty percent of the cases evolve into chronic cardiomyopathy (CCC) with worse prognosis as compared with other cardiomyopathies. In vivo bioenergetic analysis and ex vivo proteomic analysis of myocardial tissues highlighted worse mitochondrial dysfunction in CCC, and previous studies identified nuclear-encoded mitochondrial gene variants segregating with CCC. Here, we assessed the role of the mitochondrial genome through mtDNA copy number variations and mtDNA haplotyping and sequencing from heart or blood tissues of severe, moderate CCC and asymptomatic/indeterminate Chagas disease as well as healthy controls as an attempt to help decipher mitochondrial-intrinsic genetic involvement in Chagas disease development. We have found that mtDNA copy number was significantly lower in CCC than in heart tissue from healthy individuals, while blood mtDNA content was similar among asymptomatic Chagas disease, moderate and severe CCC patients. MtDNA haplogrouping study has indicated that African haplogroups were over represented in the Chagas subject groups in comparison with Brazilian healthy individuals. The European lineage is associated to protection against cardiomyopathy and the macro haplogroup H is associated with increased risk towards CCC. By mitochondria DNA sequencing, 84 mtDNA-encoded protein sequence pathogenic variants were associated with CCC. Among them, two variants were associated to left ventricular non-compaction and two to hypertrophic cardiomyopathy. The finding that mitochondrial protein-coding SNPs and mitochondrial haplogroups associate with risk of evolving to CCC is consistent with a key role of mitochondrial DNA in the development of Chronic Chagas disease Cardiomyopathy.

A crewed mission to and from Mars may include an exciting array of enabling biotechnologies that leverage inherent mass, power, and volume advantages over traditional abiotic approaches. In this perspective, we articulate the scientific and engineering goals and constraints, along with example systems, that guide the design of a surface biomanufactory. Extending past arguments for exploiting stand-alone elements of biology, we argue for an integrated biomanufacturing plant replete with modules for microbial \textit{in situ} resource utilization, production, and recycling of food, pharmaceuticals, and biomaterials required for sustaining future intrepid astronauts. We also discuss aspirational technology trends in each of these target areas in the context of human and robotic exploration missions in the coming century.

This work mapped the research chronology and conceptual trends on conservation agriculture-soil health-sustainable development goals nexus by analyzing data from related literature. This is the first-time different bibliometric methods such as VOSviewer, Flourish, as well as Bibliometrix and Biblioshiny models in RStudio were simultaneously used to investigate the research impacts and/or interactions between conservation agriculture (CA), soil health and sustainable development at global scale. On 20th February 2024, a search was launched on the web of science core collection using related search terms to extract relevant data. After the screening and elimination, the search produced 835 papers which were used in the bibliometric analysis. The revealed that USA (31%), India (27%), Australia (7%), England (6%), China (6%), Canada (5%), and other countries had below 5% of the published documents. Many of the papers covered zero hunger (38%), climate action (30%), life on land (26%), while other SDGs had relatively low coverage. The study found the adoption of no till, cover cropping, and organic amendments by the authors as the common CA practices. The hybrid bibliometric approach provided a clear roadmap in understanding the global research trajectory on CA-soil health and SDGs nexus, as well as the roles of countries, authors, institutions, publishing journals. This knowledge could support in championing future debates on CA potential for effective discussion and policies, especially in the developing countries where there have been low publications.

Zoo conditions are unique for reindeer, since even domestic reindeer are not kept in captive facilities like cattle. In the zoo, reindeer are usually surrounded by many different animals they would never encounter naturally. Thus they might pick up some new helminths. Numerous petting zoos raise an issue of safety of tactile communications for human visitors. Out study is the first large-scale one. Qualitative and quantitative fecal analysis was carried out for 233 reindeer distributed over 50 Russian zoos according to National Standard of the Russian Federation (GOST R 54627-2011) Ruminant animals—Methods of Laboratory Helminthological Diagnostics. Where possible, DNA analyses of helminths were performed targeting internal transcribed spacer region. In result, F. hepatica, Paramphistomum sp., Moniezia sp. (including M. expansa), gastrointestinal strongylids (including Nematodirus spp.), Dictyocaulus sp., E. rangiferi, Trichuris sp., and Capillaria sp. were found in 106 (45%) zoo reindeer. All these helminths were previously reported for reindeer and pose no direct danger for humans. Intensity of invasions was mostly low. Fecal examination might be considered as an indirect method for mange diagnostics, as Chorioptes and Demodex mites were found in reindeer fecal samples. The latter may represent a novel species of mite specific for reindeer.

Background: The coexistence of HIV infection and latent tuberculosis infection (LTBI) presents a significant public health concern due to the increased risk of tuberculosis (TB) reactivation and progression to active disease. The multicenter observational cohort study, TUBHIVIT, conducted in Italy from 2017 to 2023, aimed to assess the prevalence of LTBI among people living with HIV (PLHIV) and their outcomes following LTBI screening and therapy initiation. Methods: We performed a prospective study in 5 referral centers for HIV care in Italy. PLHIV who consented to participate underwent QuantiFERON-TB Gold Plus and clinical, microbiological, and radiological assessments to exclude subclinical tuberculosis, as opportune. PLHIV diagnosed with LTBI that started chemoprophylaxis were followed until the ending of therapy. Results: A total of 1105 PLHIV were screened for LTBI using the QuantiFERON-TB Gold Plus test, revealing a prevalence of 3.4% of positive results (38/1105). Non-Italy-born individuals exhibited a significantly higher likelihood of testing positive. Thirty-one were diagnosed with LTBI, 1 showed active subclinical TB, 6 were lost to follow-up before discriminating between latent and active TB. Among PLHIV diagnosed with LTBI, 83.9% (26/31) started chemoprophylaxis. Most individuals received 6-9 months of isoniazid-based therapy. Of the 26 PLHIV commencing chemoprophylaxis, 18 (69.2%) completed the therapy, while 3 discontinued it and 5 were still on treatment at the time of the analysis. Adverse events were observed in two cases, while in one case the patient refused to continue the treatment.

A number of studies suggested that influenza vaccination can provide protection against COVID-19 but the underlying mechanisms that could explain this association is still unclear. In this study, the effect of the 2021/2022 seasonal influenza vaccination on the immune response to the booster dose of anti-SARS-CoV-2 vaccination was evaluated in a cohort of healthy individuals. One hundred and thirteen participants were enrolled, and 74 of them with no prior COVID-19 diagnosis or significant co-morbidities were considered for the analysis. Participants received the anti-influenza tetravalent vaccine and the booster dose of the anti-SARS-CoV-2 vaccine or the anti-SARS-CoV-2 vaccine alone. Blood was collected before and 4 weeks after each vaccination and 12 weeks after SARSCoV2 vaccination and analyzed for anti-flu and anti-spike-specific antibody titers and for in vitro influenza and SARS-CoV-2 neutralization capacity. Results indicated an increased reactivity in subjects who received both influenza and SARSCoV2 vaccinations, as compared to those who received only the SARS-CoV-2 vaccine, with sustained anti-spike antibody titers up to 12 weeks post-vaccination. Immune response to influenza vaccine was evaluated and individuals were stratified as high or low responders. High responders showed increased antibody titers against SARSCoV2 vaccine both after 4- and 12-weeks post-vaccination. On the contrary, the individuals classified as low responders were less responsive to the SARS-CoV-2 vaccine. These data indicate that both external stimuli, such as influenza vaccination, and the host's intrinsic ability to respond to stimuli play a role in the response to vaccine.

Solar neutrinos have played a central role in the discovery of the neutrino oscillation mechanism. They still are proving to be a unique tool to help investigate the fusion reactions that power stars and further probe basic neutrino properties. The Borexino neutrino observatory has been operationally acquiring data at Laboratori Nazionali del Gran Sasso in Italy since 2007. Its main goal is the real-time study of low energy neutrinos (solar or originated elsewhere, such as geo-neutrinos). The latest analysis of experimental data, taken during the so-called Borexino Phase-II (2011-present), will be showcased in this talk - yielding new high-precision, simultaneous wide band flux measurements of the four main solar neutrino components belonging to the "pp" fusion chain (pp, pep, ⁷Be, ⁸B), as well as upper limits on the remaining two solar neutrino fluxes (CNO and hep).

Aging-related disorders pose significant challenges due to their complex interplay of physiological and metabolic factors, including inflammation, oxidative stress, and mitochondrial dysfunction. Curcumin, a natural compound with potent antioxidant and anti-inflammatory properties, has emerged as a promising candidate for mitigating these age-related processes. However, gaps in understanding the precise mechanisms of curcumin's effects and the optimal dosages for different conditions necessitate further investigation. This systematic review synthesizes current evidence on curcumin's potential in addressing age-related disorders, emphasizing its impact on cognitive function, neurodegeneration, and muscle health in older adults. By evaluating the safety, efficacy, and mechanisms of action of curcumin supplementation, this review aims to provide insights into its therapeutic potential for promoting healthy aging. A systematic search across three databases using specific keywords yielded 2,256 documents, leading to the selection of 15 clinical trials for synthesis. Here we highlight the promising potential of curcumin as a multifaceted therapeutic agent in combating age-related disorders. The findings of this review suggest that curcumin could offer a natural and effective approach to enhancing the quality of life of aging individuals. Further research and well-designed clinical trials are essential to validate these findings and optimize the use of curcumin in personalized medicine approaches for age-related conditions.

This cross-sectional, analytical, and observational study aimed to investigate the relationship between Visceral Adiposity Index (VAI) and anthropometric, biochemical, and insulin resistance (IR) parameters in Brazilians at risk of CVD. Biochemical parameters and anthropometric measurements were evaluated. The Pearson test was used to assess the correlation between VAI and anthropometric, biochemical, and IR parameters, with a predefined significance level of 5%. The analyzed sample consisted of 88 men and 72 women, with an average age of 58.78±13.48. VAI revealed noteworthy and positive correlations with all anthropometric parameters assessed (p&lt;0.0001). Furthermore, significant positive associations were noted between VAI and total cholesterol in women (p=0.0064), glycemia in men (p=0.0105), and LDL-c (p&lt;0.01) and triglycerides in both genders (p˂0.0001). A significant negative association was observed between VAI and HDL-c in both genders (p&lt;0.0001). Notably, the correlation between VAI and total cholesterol in men, glycemia in women, and CRP in both genders was not found to be significant. However, a significant relationship between VAI and IR parameters was observed in both sexes (p&lt;0.05). The results obtained from our study suggest that VAI functions as a simple and non-intrusive instrument, demonstrating significant effectiveness in identifying metabolic changes primarily associated with adipose tissue dysfunction, particularly dyslipidemia.

Some glucagon-like peptide-1 receptor agonists (GLP-1 RAs), first used in the treat-ment of type 2 diabetes mellitus (T2DM), have been approved for the treatment of obe-sity in patients with or without T2DM (liraglutide – LIR, semaglutide - SEM, and tir-zepatide - TIR). Social media had an important influence on the off-label use of GLP-1 RAs for obesity, especially for SEM. We analysed the Google queries related to SEM to assess people's interest in this drug. We also investigated the occurrence of adverse drug reactions (ADRs) by searching the EudraVigilance database (EV) for Individual Case Safety Reports (ICSRs) that reported SEM as the suspected drug and performed a descriptive and a disproportionality analysis. Data obtained for SEM were compared to other GLP-1 RAs. SEM had the highest proportions of searches on Google associated with the term “weight loss” and presented the lowest number of severe ADRs, but it also had the highest number of ICSRs reported in EV. Even though no unexpected safety issues have been reported for it until now, SEM has a high tendency for overdose reports. The most frequent off-label use was reported for SEM and TIR. In order to lower the ADRs’ risks, the off-label use should be reduced and carefully monitored.

MicroRNAs (miRNAs), particularly miR-16 and miR-21, play a crucial role in mul-tiple myeloma (MM) pathogenesis by regulating gene expression. This study evalu-ated the prognostic significance of circulating miR-16 and miR-21 expression levels in 48 patients with MM at diagnosis treated with lenalidomide/dexamethasone (LD) compared with 15 healthy individuals (HI). All patients were treated with LD, 13 at first line and 35 at relapse, of whom 21 were tested twice at diagnosis and before LD initiation. The results revealed significantly lower levels of miR-16 and miR-21 in patients than in HIs, both at diagnosis and relapse, with decreased miR-16 levels at diagnosis, indicating improved overall survival (OS) (p value 0.024). Furthermore, miR-16 and miR-21 levels were associated with disease markers, while both corre-lated with the depth of response and mir-16 with sustained response to LD treatment. The ratios of both miR-16 and miR-21 expression levels (prior to LD treat-ment/diagnosis) below 2 predicted a shorter time to response (P = 0.027) and a longer time to next treatment (P = 0.042), respectively. These findings suggested a prognostic value for serum miR-16 and miR-21 levels in MM, as their expression levels corre-lated with disease variables and treatment outcomes.

An imbalance between production and excretion of amyloid β peptide (Aβ) in the brain tissues of Alzheimer’s disease (AD) patients leads to Aβ accumulation and formation of noxious Aβ oligomers/plaques. A promising approach to AD prevention is reduction of free Aβ level by directed enhancement of Aβ binding to its natural depot, human serum albumin (HSA). We previously demonstrated the ability of specific low-molecular-weight ligands (LMWLs) of HSA to improve its affinity for Aβ. Here we develop this approach by bioinformatic search for the clinically approved AD-related LMWLs of HSA, followed by classification of the candidates according to the predicted location of their binding sites on HSA surface, ranking of the candidates, and selective experimental validation of their impact on HSA affinity for Aβ. The top 100 candidate LMWLs were classified into the five clusters. The specific representatives of the different clusters exhibit dramatically different behavior, with 3- to 13-fold changes in equilibrium dissociation constants for the HSA-Aβ40 interaction: prednisone favors HSA-Aβ interaction, mefenamic acid shows the opposite effect, while levothyroxine exhibits the bidirectional effects. Overall, the LMWLs of HSA chosen here provide a basis for drug repurposing for AD prevention, and for search for the medications promoting AD progression.

Nature-Based Solutions (NBSs) can help to achieve multiple Water-Ecosystem-Food Nexus Do-main Objectives & Nexus Resilience Qualities, facilitating the transition to more resilient agrifood systems and providing an evidence base for a broader Nexus policy dialogue. This paper de-scribes the stepwise methodology developed in the EU-funded LENSES project to carry out a comprehensive analysis of NBSs in 6 pilot areas in 5 Mediterranean countries, and presents the results of NBSs implementation in 4 pilot areas, highlighting obstacles and opportunities. The methodology includes the development of an analytical evaluation framework and of a com-prehensive catalogue of Nexus-related NBSs, whose suitability needs to be assessed at the local level to achieve better use of protected/natural ecosystems, increase the sustainability and mul-tifunctionality of managed ecosystems and design and manage novel ecosystems. Subsequently, in a collective learning process which supported the operationalisation of the WEF Nexus, NBSs were identified that address specific contextual vulnerabilities, improve water distribution and enhance food security, while preserving ecosystems and supporting adaptation to climate change. The added value of the proposed methodology lies in the multi-stakeholder participatory approach to gain in-depth knowledge of local agri-food systems, including their main WEF-related challenges, and to facilitate overcoming barriers to NBS implementation.

Rapid and continuing advances in biomarker testing are not being matched by take-up in health systems, and this is hampering both patient care and innovation. It also risks costing health systems the opportunity to make their services more efficient and, over time, more economical. The potential that genomics has brought to biomarker testing in diagnosis, prediction and research is being realised, pre-eminently in many cancers, but also in an ever-wider range of conditions. One of the paradigmatic examples is BRCA1/2 testing in ovarian, breast, pancreatic and prostate cancers. Nevertheless, development is impeded by data deficiencies, and lack of policy alignment on standards, approval – and the role of real-world evidence in the process - and reimbursement. The acute nature of the problem is compellingly illustrated by the particular challenges facing the development and use of tumour agnostic therapies, where the gaps in preparedness for taking advantage of this innovative approach to cancer therapy are sharply exposed. Europe should already have in place a guarantee of universal access to a minimum suite of biomarker tests and should be planning for an optimum testing scenario with a wider range of biomarker tests integrated into a more sophisticated health system articulated around personalised medicine. Improving healthcare and winning advantages for Europe's industrial competitiveness and innovation require an appropriate policy framework – starting with an update to outdated recommendations.

Background: Malnutrition commonly affects patients with oral squamous cell carcinoma (OSCC), which contributes to worsening prognosis. Moreover, specific strategies for diagnosing and managing malnutrition in OSCC are lacking. Methods: This retrospective study included 52 consecutive patients with OSCC who underwent surgery at the University Hospital of Palermo (I) from Jan 2020 to May 2023. In-hospital nutritional support was provided by a dedicated team. The patients were compared with a historical control group of 11 patients. The nutritional treatment consisted of standard oral (ON) or artificial nutrition (AN). Traditional measurements, including bioimpedance-derived body composition and volumetric reconstruction of the posterior paraspinal muscles at the C3 level based on magnetic resonance imaging (MRI-C3), were obtained in 16 patients to investigate sarcopenia. Results: The patients were categorized according to TNM stage: groups A (TNM stages I-III) and B (IVa-IVc). The prevalence of group A patients was 59.6% in the case group and 90.9% in the control group (P

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.

S5 0716+714 is a well known BL-Lac object, one of the brightest and most active blazars. The discovery in the Very High Energy band (VHE, E > 100 GeV) by MAGIC happened in 2008. In January 2015 the source went through the brightest optical state ever observed, triggering MAGIC follow-up and a VHE detection with ~ sigma significance (ATel #6999). Rich multi-wavelength coverage of the flare allowed us to construct the broad-band spectral energy distribution of S5 0716+714 during its brightest outburst. In this work we will present the preliminary analysis of MAGIC and Fermi-LAT data of the flaring activity in January and February 2015 for the HE and VHE band, together with radio (Metsahovi, OVRO, VLBA, Effelsberg), sub-millimeter (SMA), optical (Tuorla, Perkins, Steward, AZT-8+ST7, LX-200, Kanata), X-ray and UV (Swift-XRT and UVOT), in the same time-window and discuss the time variability of the MWL light curves during this impressive outburst.

Pathogenicity of many bacteria including Bacillus cereus and Staphylococcus aureus depends on pore-forming toxins (PFTs), which cause lysis of host cells by forming pores in membranes of eukaryotic cells. Bioinformatic analysis revealed in over 600 PFTs a region homologous to the Lys171-Gly250 sequence in hemolysin II (HlyII) from B. cereus, which we designated as “homologous peptide”. Three β-barrel PFTs were used for a detailed comparative analysis. Two of them –HlyII and cytotoxin K2 (CytK2), – are synthesized in Bacillus cereus sensu lato; the third – S. aureus α-toxin (Hla) – is the most investigated representative of the family. Protein modeling showed certain amino acids of homologous peptide to be located on the surface of the monomeric forms of these β-barrel PFTs. We obtained monoclonal antibodies against both a cloned homologous peptide and a 14-membered synthetic peptide DSFNTFYGNQLFMK as part of homologous peptide. The HlyII, CytK2 and Hla regions recognized by the obtained antibodies, as well as an antibody capable of suppressing the hemolytic activity of CytK2, were identified in the course of the work. Antibodies capable of recognizing PFTs of various origins can be useful tools for both identification and suppression of the cytolytic activity of PFTs.

Newborn screening using biochemical tests is a widespread practice. However, the recent availability of genetic sequencing has enabled the rapid screening of many monogenic disorders. The purpose of our study was to assess the outcomes of whole exome sequencing (WES) and whole genome sequencing (WGS) as the primary newborn screening test. This cohort study enrolled 26 symptomatic neonates and infants exhibiting a spectrum of neurological symptoms and issues. Genome sequencing (GS) identified relevant diagnostic variants in 9 patients (point mutations, CNVs and one case of aneuploidy), suggesting that using GS as the primary newborn screening test in a general newborn population enhances traditional screening's detection capabilities. This evidence-based finding may support considering GS as a critical method for first-tier screening.

Aflatoxin being a serious threat to public health and international trade, necessi-tates a comprehensive understanding and calculated response with effective inter-vention strategies. This review methodically looks at several aspects of aflatoxin, starting with how it affects international trade laws through feed and feed ingre-dient regulations. Aflatoxin contamination poses serious challenges to world health and the economy, especially in areas that are already at risk. Examining the varia-bles affecting aflatoxin toxicity, the paper clarifies aflatoxin toxicity's complex me-tabolism and the resulting health effects of exposure. The serious repercussions of aflatoxicosis outbreaks and their connections to illnesses like Aspergillosis and cancer are highlighted by a detailed exploration of prospective decontamination techniques as well as strategies for detecting and capturing aflatoxin. A thorough knowledge of the factors that contribute to aflatoxin contamination demonstrates the intricate interactions between environmental variables, farming methods, stor-age circumstances, and different physical, biological, and nutritional components. Strong detection strategies are required due to aflatoxins’ significant effects on an-imal and human health. The paper describes complete preventative tactics that en-compass manipulation in management strategies. global trade and public health from this pervasive threat.

Pharmacy compounding, the art and science of preparing customized medications to meet individual patient needs, is in a verge of transformation. Traditional methods of compounding often involve manual and time-consuming processes, presenting challenges in terms of consistency, dosage accuracy, quality control, contamination and scalability. However, the emergence of cutting-edge technologies has paved a way for a new era for pharmacy compounding, promising to redefine the way medications are prepared and delivered as pharmacy-tailored personalized medicines. In this multi-site study, more than 30 hospitals and community pharmacies from 8 countries in Europe utilized a novel automated dosing approach inspired by 3D printing for compounding of non-sterile propranolol hydrochloride tablets. CuraBlend® excipient base, a GMP manufactured pharma-ink, intended for automated compounding applications was used. A standardized study protocol to test the automated dosing of tablets with variable weights was performed in all participating pharmacies in 4 different iterative phases. Integrated quality control was performed with an in-process scale and NIR spectroscopy supported by HPLC content uniformity measurements. In total, 6088 propranolol tablets were produced at different locations during this study. It was shown that the dosing accuracy of the process increased from about 90% to 100% from phase 1 to phase 4 by making improvements to the formulation and the hardware solutions. The results indicate that through this novel automated and quality-controlled compounding approach extemporaneous pharmacy manufacturing can take a giant leap forward towards automation and digital manufacture of dosage forms in hospital pharmacies and compounding pharmacies.

We analyse the light curve in the R-band gathered during the 2015/16 observing season of OJ287. We did a search for QPOs using several methods in wide time domain. No statistically significant periods were found in the high frequency domain both in the ground data and also in K2 observations. In the longer periods domain the Lomb-Scargle periodogram revealed several peaks above the 99\% significance level. The longest one, about 95-day, corresponds to the ISCO period of the more massive SMBH. The 43-day period could be an alias or can be attributed to accretion in the form of two armed spiral wave.

Ocean exploration is crucial for utilizing its extensive resources. Images captured by underwater robots suffer from issues such as color distortion and reduced contrast. To address the issue, we propose an innovative enhancement algorithm that integrates Transformer and Convolutional Neural Network (CNN) in a parallel fusion manner. Firstly, a novel transformer model is intro-duced to capture local features, employing peak-signal-to-noise ratio (PSNR) attention and linear operations. Subsequently, to extract global features, both temporal and frequency domain features are incorporated to construct convolutional neural network. Finally, the Fourier’s high and low-frequency information of the original image are utilized to fuse different features. To demon-strate the algorithm's effectiveness, underwater images with various levels of color distortion are selected for both qualitative and quantitative analyses. The experimental results demonstrate that our approach surpasses other mainstream methods, achieving superior PSNR and structural sim-ilarity index measure (SSIM) metrics and leading to a detection performance improvement of over ten percent.

Leukocyte migration is an essential function of innate and adaptive immune responses. Chemokines and their receptors control the migration system. The abundance of chemokines is controlled by atypical chemokine receptors (ACKRs), chemokine receptor-like molecules that do not couple to the G protein signaling pathways. Among them, ACKR4 regulates dendritic cell migration by controlling the ligands and is involved in tumor development in mouse models. Because no anti-mACKR4 mAb for flow cytometry has been reported, this study aimed to develop a novel monoclonal antibody (mAb) for mouse ACKR4 (mACKR4). Among the established anti-mACKR4 mAbs, A₄Mab-1 (rat IgG_2b, kappa), A₄Mab-2 (rat IgG_2b, kappa), and A₄Mab-3 (rat IgG_2b, kappa) recognized mACKR4-overexpressed Chinese hamster ovary-K1 (CHO/mACKR4) by flow cytometry. The dissociation constant (K_D) values of A₄Mab-1, A₄Mab-2, and A₄Mab-3 for CHO/mACKR4 were determined as 3.5 × 10⁻⁹ M, 6.0 × 10⁻⁹ M, and 1.6 × 10⁻⁹ M, respectively. Furthermore, A₄Mab-1 and A₄Mab-2 could detect mACKR4 by western blotting. These results indicated that A₄Mab-1, A₄Mab-2, and A₄Mab-3 help to detect mACKR4 by flow cytometry and western blotting and obtain the proof of concept in preclinical models.