Buttonweed (Cotula coronopifolia) is native to South Africa but invasive in wetlands in Europe, North America, and Australasia, where it excludes native plants. Despite being dry-fruited, field studies suggest migratory waterbirds can disperse its seeds via gut passage (endozoochory), aiding its expansion. To explore the potential for endozoochory in different regions and habitats, we collected seeds from six populations in Spain, Sweden, and the UK. Germination was tested under different salinity levels (0, 5, 10, 15 g/L) and simulated gut passage treatments: scarification, acidification, or both. No germination occurred at 15 g/L. Higher salinity reduced and delayed germination, but full gut passage treatment increased germinability and accelerated germination. Scarification or acid treatment alone resulted in intermediate germination patterns. There were significant salinity x population and gut passage x population interactions on germinability. The acceleration effect of gut passage on germination was stronger at 5-10 g/L than at 0 g/L. This study highlights how migratory birds can facilitate the spread of alien plants introduced by humans. Non-classical endozoochory by waterbirds is an understudied mechanism for the long-distance dispersal of dry-fruited alien plants. Further research on C. coronopifolia, including population genetics, is necessary to understand dispersal mechanisms and facilitate management strategies.

Chronic exposure to the nephrotoxic metal pollutant, cadmium (Cd), has been associated with hypertension, but the mechanism by which it raises blood pressure is not understood. We hypothesize that exposure to Cd reduces the glomerular filtration rate (GFR), which in turn, causes a rise in blood pressure. Data were collected from 447 Thai subjects with a mean age of 51.1 years, of which 48.8% had hypertension, 15.4% had diabetes and 6.9% had an estimated GFR (eGFR) below 60 mL/min/1.73 m2 (low eGFR). The mean blood and urinary Cd concentrations were 2.75 and 4.23 µg/L, respectively. The prevalence odds ratio (POR) for hypertension rose twofold in those with blood Cd levels of 0.61-1.69 µg/L or urinary Cd excretion levels ≥ 0.98 µg/g creatinine. In the hypertensive group, the eGFR was inversely associated with age (β =−0.517), the Cd excretion rate (β = −0.177), and diabetes (β = −0.175). Mean eGFR in the normotensive group was 7.5 mL/min/1.73 m2 higher than the hypertensive with a similar Cd body burden. Mean systolic blood pressure (SBP) in those with low or medium eGFR plus heavy Cd body burden was 9.5 mmHg higher than those with the same Cd body burden and a normal eGFR. By mediation analysis, a 22.7% increase in SBP and a 5% increase in diastolic blood pressure (DBP) were attributable to the effect of Cd on GFR. Thus, a rise of blood pressure appears to be a consequence of GFR loss due to Cd-induced kidney damage. This finding is consistent with a well-known role of the kidney in long-term blood pressure regulation.

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

Undernutrition and micronutrient deficiencies such as anemia are considered significant public health challenges in Bangladesh, which enhancing fish consumption is a well-established food-based intervention to address these. This paper documents the establishment of community-based fish chutney production and reports the impact of its consumption on mid-upper arm circumference (MUAC) and hemoglobin (Hb) levels among targeted 150 pregnant and lactating women (PLW) in rural Bangladesh. A fish chutney was developed using locally available ingredients followed by a series of laboratory tests, including nutrient composition, shelf-life and food safety. A community-based fish chutney production process was designed to: 1) supply locally available ingredients for processing; 2) establish two fish drying sites; 3) initiate a community-based production site, and 4) distribute fish chutney to PLW by six women nutrition field facilitators for one year. Then a pre- and post-intervention study was designed for a selected 150 PLW to receive 30g of fish chutney daily for 12 months. Differences in mean mid-upper arm circumference (MUAC) and hemoglobin (Hb) levels pre- and post-consumption were analyzed using one-way analysis of variance. Consumption of 30g of fish-chutney resulted in significant increases of the mean values of Hb levels and MUAC among the targeted PLW.

High resolution information on nucleotide arrangement in the genome of any or-ganism is critical to understand its genetic makeup, function, and evolutionary his-tory. For years, DNA sequencing has provided crucial breakthroughs in the field of genomics and molecular biology. With the advent of technology, Next Generation Sequencing has now transformed the whole genome sequencing prospects, thus unveiling the novel and interesting features of an organism genome that can behold. Next generation sequencing platforms offer realistic approach to identify and anal-yses whole genome with high throughput, accuracy, scalability in a very short time span. Information obtained can be further used in improving our existing healthcare systems, designing novel and personalized therapeutic modules, making the envi-ronment sustainable and proactively preparing ourselves for future pandemics and outbreaks. This article discusses the various NGS technologies and approaches, their advantages, drawbacks, and futuristic usage in different fields. Though still in nascent stages and marred with flaws, with ongoing advancement, NGS will indeed have promising impacts in the future.

Respiratory syncytial virus (RSV) infection is a major cause of severe respiratory disease in infants and young children worldwide. Two vaccines targeting the elderly and pregnant women have been recently approved employing the prefusion form of the RSV-fusion protein (F). However, there are currently no vaccines for infants. Studies have shown a fusion-inactive prefusogenic F form is significantly more immunogenic and produces higher antibody titers to both the prefusion and postfusion structures of the F protein. Here we have developed RSV virus-like particles (RSV-VLPs) consisting of prefusogenic F, RSV glycoprotein and matrix proteins, produced them using the baculovirus expression system, and studied their protective efficacy in Balb/c mice. Morphology and successful assembly of VLPs were confirmed by transmission electron microscopy and western blot. Mice immunized with VLPs developed high levels of serum IgG and neutralizing antibodies as compared with mice immunized with inactivated virus. The VLP vaccine also induced higher levels of IFNγ and IL4, elicited limited proliferation of CD4+ and CD8+ T cells but higher cytotoxic-T-lymphocyte responses. VLP immunization abolished lung pathology in the mice after RSV challenge. Overall, our results indicate that RSV-VLPs consisting of prefusogenic F, glycoprotein and matrix proteins are a potential vaccine candidate against RSV.

In a hyperconnected society, computer networks play a pivotal role in all activities that permeate our daily lives. In the context of smart cities, theses networks play a pivotal role in enhancing urban efficiency and sustainability. The continuous flow of packets in these networks poses security challenges, from personal data leakage to service unavailability. Anomaly-based methods are commonly used to detect network attacks. In this context, Software-Defined Networking (SDN) emerges as a solution for anomaly detection in network traffic, facilitating comprehensive, real-time analyses and dynamic adaptation to changes. This study aims to present a systematic review of feature selection techniques and evaluate the effectiveness of attribute selection with a multi-class classifier in network anomaly detection. The objective of this paper is to inspire future research and identify trade-offs among these techniques for detecting Denial of Service (DoS) attacks. Based on the findings, the analysis of the entire dataset yields superior results in terms of precision (99%), but using the output of OneR, although resulting in a slight loss of precision compared to the complete dataset, presents the highest precision among other studied techniques, indicating a trade-off between precision and processing time efficiency.

Change Detection (CD) of aerial images refers to identifying and analyzing changes between two or more aerial images of the same location taken at different times. The CD is a highly challenging task due to the need to distinguish relevant changes, such as urban expansion, deforestation, or post-disaster damage assessment, from irrelevant ones, such as light conditions, shadows, and seasonal variations. Many CD papers have recently been published, where most of the papers that proposed a new model contained a comparison between their proposed and state-of-the-art (SOTA) models. While many recent studies propose new deep learning (DL) models for improving CD performance, their comparative analyses are often restricted, lacking comprehensive insights into the proposed models' real-world generalizability, robustness, and performance trade-offs across diverse change characteristics. This paper presents a novel generic framework to systematically benchmark and assess DL-based CD models through three parallel pipelines: 1) cross-testing models on diverse benchmark datasets to evaluate generalization, 2) robustness analysis against different image corruptions, and 3) multi-faceted contour-level analytics evaluating detection sensitivity to change size/complexity. The framework is applied to comparatively evaluate five state-of-the-art DL-based CD models - Changeformer, BIT, Tiny, SNUNet, and CSA-CDGAN. Extensive experiments unveil each model's strengths, limitations and biases, highlighting their relative proficiencies in generalizing across data distributions, resilience to noise corruption, and discriminative capabilities for changes of varying characteristics. The proposed benchmarking framework demonstrates significant potential for guiding the selection of suitable CD models tailored to specific application requirements by comprehensively evaluating their generalizability, robustness, and detection capabilities across diverse real-world scenarios. This systematic evaluation approach can drive future research into developing more robust and versatile CD solutions aligned with practical needs.

Tumid Lupus Erythematosus has been the subject of heated debate as to its correct nosographic classification. In particular, its definition has changed over time, depending on the different studies performed. In this review we address the initial definition of TLE, the changes that have taken place in the understanding and placement within the classification of Lupus Erythematosus (LE), and focus on clinical, histopathological, immunophenotypical and differential diagnosis aspects.

We propose a spectral filter based on Plastic Optical Fiber with micro-holes as a low-cost, robust, and highly reproducible spectral filter. The spectral filter is explored for two configurations: fiber extended in a straight line, and a fiber optic loop mirror scheme configuration. The transmission traces indicate a spectral blue shift of peak transmission, at 587 nm, 567 nm, 556 nm, and 536 nm for 0, 1, 2, and 3 holes in the fiber, respectively. The filter exhibits a bandpass period of approximately 120 nm. Additionally, we conducted a comparison of the transmission with holes separated by distances of 1 cm and 500 μm. The results demonstrate that the distance between holes does not alter the spectral transmission of the filter. In the case of the fiber loop mirror configuration, we observed that the bandpass can be adjusted, suggesting the presence of multimode interference. Exploring variations in the refractive index within the holes by filling them with glucose solutions at various concentrations, we determined that the filtering band and spectral shape remains unaltered, ensuring a stable and robust operation of our spectral filter.

Cannabis sativa is one of the oldest plants utilized by humans for both economic and medical purposes. Although the use of cannabis started millennia ago in the Eastern part of the hemisphere, its use has moved and flourished in the Western Nations in more recent centuries. C. sativa is the source of psychoactive cannabinoids that are consumed as recreational drugs worldwide. The C21 aromatic hydrocarbons are restricted in their natural occurrence to cannabis (with a few exceptions). Delta-9-tetrahydrocannabinol (Δ9-THC) is the main psychoactive component in cannabis with many pharmacological effects and various approved medical applications. However, a wide range of side effects are associated with the use of Δ9-THC, limiting its medical use. In 1966, another psychoactive cannabinoid, Delta-8-tetrahydrocannabinol (Δ8-THC) was isolated from marijuana grown in Maryland but in very low yield. Δ8-THC is gaining increased popularity due to its better stability and easier synthetic manufacturing procedures compared to Δ9-THC. Passing the U.S. Farm Bill in 2018 led to an increase in the sale of Δ8-THC in the United States. The marketed products contain Δ8-THC from synthetic sources. In this review, methods of extraction, purification, and structure elucidation of Δ8-THC will be presented. The issue of whether Δ8-THC is a natural compound or an artifact will be discussed, and the different strategies for its chemical synthesis will be presented. Δ8-THC of synthetic origin is expected to contain some impurities due to residual amounts of starting materials and reagents as well as side products of the reactions. The various methods of analysis and detection of impurities present in the marketed products will be discussed. The pharmacological effects of Δ8-THC, including its interaction with CB1 and CB2 cannabinoid receptors in comparison with Δ9-THC, will be reviewed.

The ability of recombinant, SARS-CoV-2 Spike (S) protein to modulate the production of two COVID-19 relevant, pro-inflammatory cytokines (IL-6 and IFN-γ) in PBMC cultures of healthy, pre-Covid-19 subjects was investigated. We observed that cytokine production was largely and diversely modulated by the S protein depending on antigen or mitogen stimulation, as well as on the protein source, insect (S-in) or human (S-hu) cells. While both proteins co-stimulated cytokine production by polyclonally CD3-activated T cells, PBMC activation by the mitogenic lectin Concanavalin A (Con A) was up modulated by S-hu protein and down-modulated by S-in protein. These modulatory effects were likely mediated by the S glycans as demonstrated by direct Con A-S binding experiments and use of yeast mannan as Con A binder. While being ineffective in modulating memory antigenic T cell responses, the S proteins and mannan were able to induce IL-6 production in unstimulated PBMC cultures and upregulate the expression of Mannose Receptor (CD206), a marker of anti-inflammatory M2 macrophage. Our data point to a relevant role of N-glycans, particularly N-mannosidic chains, decorating the S protein in the immunomodulatory effects here reported. These novel biological activities of the S glycan ectodomain may add to the comprehension of Covid-19 pathology and immunity to SARS-CoV-2.

Increasing HIV drug resistance (DR) among children with HIV (CHIV) on antiretroviral treatment (ART) is concerning. CHIV ages 1-14 years enrolled March 2019 to December 2020 from five facilities in Kisumu County, Kenya were included. Children were randomized 1:1 to control (standard-of-care) or intervention (point-of-care viral load (POC VL) testing every three months with targeted genotypic drug resistance testing (DRT) for VF (> 1000 copies/ml)). A multidisciplinary committee reviewed CHIV with DRT results and offered treatment recommendations. We describe DR mutations and present logistic regression models to identify factors associated with clinically significant DR. We enrolled 704 children in the study; median age was 9 years (interquartile range (IQR) 7,12), 344 (49%) were female and median time on ART was 5 years (IQR 3, 8). During the study period, 106 (15%) children had DRT results (84 intervention and 22 control). DRT detected mutations associate with DR in all participants tested, with 93 (88%) having major mutations, including 51 (54%) with dual class resistance. A history of VF in prior 2 years (adjusted odds ratio (aOR) 11.1; 95% confidence interval (CI) 6.3, 20.0) and less than 2 years on ART at enrollment (aOR 2.2; 95% CI 1.1, 4.4) were associated with increased odds of major DR. DR is highly prevalent among CHIV on ART with VF in Kenya. Factors associated with drug resistance may be used to determine which children should be prioritized for DRT.

COVID-19 is characterized by a heterogeneous clinical presentation and prognosis. Risk factors contributing to the development of severe disease include old age and the presence of comorbidities. However, the genetic background of the host has also been recognized as an important determinant of disease prognosis. Considering the pivotal role of innate immunity in the control of SARS-CoV-2 infection, we analyzed the possible contribution of several innate immune gene polymorphisms (including TLR2-rs5743708, TLR4-rs4986790, TLR4-rs4986791, CD14-rs2569190, CARD8-rs1834481, IL18-rs2043211 and CD40-rs1883832) in disease severity and prognosis. A total of 249 individuals were enrolled and further divided into five (5) groups, according to the clinical progression scale provided by the World Health Organization (WHO) (asymptomatic, mild, moderate, severe and critical). We identified that elderly patients with obesity and/or diabetes mellitus were more susceptible to developing pneumonia and respiratory distress syndrome after SARS-CoV-2 infection, while the IL18-rs1834481 polymorphism was an independent risk factor for developing pneumonia. Moreover, individuals carrying either the TLR2-rs5743708 or the TLR4-rs4986791 polymorphisms exhibited a 3.6- and 2.5-fold increased probability for developing pneumonia and a more severe disease, respectively. Our data supports the notion that the host’s genetic background can significantly affect COVID-19 clinical phenotype, also suggesting that the IL18-rs1834481, TLR2-rs5743708 and TLR4-rs4986791 polymorphisms may be used as molecular predictors of COVID-19 clinical phenotype.

Background: Current European guidelines support transcatheter aortic valve implantation (TA-VI) in intermediate to low-risk patients ≥75 years-old but its prognostic relevance is unknown. Methods: Intermediate-to-low-risk (Society of Thoracic Surgeon score <8%) patients enrolled in the HORSE registry were included. We compared the population with less versus more than 75 years old. The primary endpoint was all-cause mortality. Results: A total of 2685 patients were included, 280 (8.6%) <75 and 2405 ≥75 years. Through a mean follow-up of 437 ± 381 days, 198 (8.2%) and 23 (8.2%) patients died in the two arms, without statistically significant differences (log-rank p=0.925). At Cox regression analysis, age did not predict the occurrence of all-cause death, neither as a continuous variable (HR 1.01, 95% CI 0.99-1.04, p=0.294) nor dichotomizing according to the prespecified cutoff of 75 years (HR 0.97, 95% CI 0.63-1.51p=0.924). Time-to-event ROC curves showed low accuracy of age to predict all-cause mortality (area under the curve of 0.54 for both 1-year and 2-year outcomes). Conclusions: TAVI has comparable benefits across age strata in intermediate-to-low risk patients. The age cut-off suggested by current guidelines is not predictive of the risk of adverse events during hospital stay, neither of all-cause mortality through a mid-term follow-up.

Tick-borne encephalitis virus (TBEV) is one of the most threatening pathogens which affects the human central nervous system (CNS). TBEV circulates widely in Northern Eurasia. According to ECDC the number of TBE cases increase annually. There is no specific treatment for the TBEV infection, thus vaccination is the main preventive measure. Despite the existence of several inactivated vaccines currently being licensed, the development of new TBEV vaccines remains a leading priority in countries endemic to this pathogen. Here we report new recombinant virus made by infectious subgenomic amplicon (ISA) approach using TBEV and yellow fever virus vaccine strain (YF17DD-UN) as a genetic backbone. The recombinant virus is capable of effective replication in mammalian cells and induce TBEV-neutralizing antibodies in mice. Unlike the original vector based on the yellow fever vaccine strain chimeric virus became neuroinvasive in doses of 107-106 PFU and can be used as a model of Flavivirus neuroinvasiveness, neurotropism and neurovirulence. These properties of hybrid structures are the main factors limiting their practical use as vaccines platforms.

Objective: We aimed to clarify the differences in the association between re-admission for heart failure (HF) and left atrial (LA) overload indices by sex in heart failure and a preserved ejection fraction (HFpEF). Methods: We analysed 898 HFpEF patients hospitalized for acute decompensated HF. Blood tests and transthoracic echocardiography were performed before discharge. The primary endpoint was re-admission for HF during the first year. Results: The ratio of diastolic elastance to arterial elastance (p=0.014), a relative index of LA pressure overload, in men and LA volume index (LAVI, p=0.020) in women were significant for re-admission for HF during the first year in the multivariable Fine-Gray analysis. Stroke volume (SV)/LA volume (LAV), another index for LAV overload, was not a significant prognostic factor of re-admission for HF during this time. Conclusion: LA overload was an important prognostic factor for HF re-readmission during the first year after enrolment in patients with HFpEF, but the indices relating to LA overload differed by sex.

At least 50% of factors predisposing to alcohol dependence (AD) are genetic and women affected with this disorder present with more psychiatric comorbidities, probably indicating different genetic factors involved. We aimed to run a genome-wide association study (GWAS) followed by a bioinformatic functional annotation of associated genomic regions in male and female patients with AD and eight related clinical measures. A genome-wide significant association of rs220677 with AD (p-value = 1.33×10^-8 calculated with the Yates-corrected Chi-square test under the assumption of dominant inheritance) was discovered in female patients. Associations of AD and related clinical measures with seven other single nucleotide polymorphisms listed in previous GWAS of psychiatric and addiction traits were differently replicated in male and female patients. The bioinformatic analysis showed that regulatory elements in the eight associated linkage disequilibrium blocks define the expression of 80 protein-coding genes. Nearly 68% of these and of 120 previously published coding genes associated with alcohol phenotypes directly interact in a single network. This study indicates that a number of genes behind the pathogenesis of AD are different in male and female patients, but implicated molecular mechanisms are functionally connected. The results also suggest the genetic basis of sex-specific psychiatric comorbidities of AD.

Glial fibrillary acidic protein (GFAP) is the major intermediate filament III protein of astroglia cells which is upregulated in traumatic brain injury (TBI). Here we reported that GFAP is truncated at both the C- and N-terminals by cytosolic protease calpain to GFAP breakdown products (GBDP) of 46-40K then 38K following pro-necrotic (A23187) and pro-apoptotic (staurosporine) challenges to primary cultured astroglia or neuron-glia mixed cells. In addition, with another pro-apoptotic challenge (EDTA) where caspases are activated but not calpain, GFAP was fragmented internally, generating a C-terminal GBDP of 20 kDa. Following controlled cortical impact in mice, GBDP of 46-40K and 38K were formed from day 3 to 28 post-injury. Purified GFAP protein treated with calpain-1 and -2 generates (i) major N-terminal cleavage sites between A-56 and A-75, and (ii) major C-terminal cleavage sites between T-383 and Q-388, producing a limit fragment of 38K. Caspase-6 treated GFAP was cleaved at D-78, R-79, D-266 and A-267, where GFAP was relatively resistant to caspase-3. We also derived a GBDP-38K N-terminal-specific antibody which only labels injured astroglia cell body in both cultured astroglia and mouse cortex and hippocampus after TBI. As a clinical translation, we observed that CSF samples collected from severe human TBI have elevated levels of GBDP-38K as well as two C-terminally released GFAP peptides (DGEVIKES and DGEVIKE). Thus, in addition to intact GFAP, both the GBDP-38K as well as unique GFAP released C-terminal proteolytic peptides species might have the potential in tracking brain injury progression.

Addressing factors modulating COVID-19 is crucial since abundant clinical evidence shows that outcomes are markedly heterogeneous between patients. This requires identifying the factors and understanding how they mechanistically influence COVID-19. Here, we describe how eleven selected factors influence COVID-19 by applying the Adverse Outcome Pathway (AOP) framework well-established in regulatory toxicology. This framework aims to model the sequence of events starting from an initial interaction of a stressor with the organism and the progress through key biological events leading to an adverse health outcome. Several linear AOPs depicting pathways from the binding of the virus to ACE2 up to clinical outcomes observed in COVID-19 patients have been developed and integrated into a network offering a unique overview of the mechanisms underlying the disease. As SARS-CoV-2 infectibility and ACE2 activity are the major starting points and inflammatory response is central in the development of COVID-19, we evaluated how eleven intrinsic and extrinsic factors modulate those processes impacting clinical outcomes. Applying this AOP-aligned approach enables the identification of current knowledge gaps orientating for further research and allows to propose biomarkers to identify of high-risk patients. This approach also facilitates expertise synergy from different disciplines to address public health issues.

BACKGROUND. Two sequelae of non-alcoholic steatohepatitis (NASH), ESLD and HCC, have become the leading causes for liver transplantation in the Western. The present study aims to approach the cellular metabolic disturbances involved in NASH progression that are associated with microbiota community changes. METHODS. Metabolic effects and microbiota community changes were explored in the murine with NASH progression by blocking the Na/K-ATPase/Src/reactive oxygen amplification loop using the synthetic targeting peptide pNaKtide. DNA from the terminal ileum microbiota habitat was obtained and amplified by PCR to develop DNA bacterial phylogenic sequence analysis of wild type and treated animals at 12, 24 and 48 weeks. Induced changes by pSrc normalization at 24 weeks were correlated with liver morphological changes, intestinal CD4+/CD8+ ratio, and liver macrophage CD14+ expression. Differences among groups were evaluated by ANOVA/t-test and Principal Component Analysis (PCA). RESULTS. Microbiota communities varied significantly at all time points (12, 24 and 48 weeks), with an increase of Verrucomicrobia and a decrease of Bacteroidetes and Firmicutes in the HFD group. Microbiota community changes regressed to their wild-type state at 24 weeks on treated animals, and those changes were associated with a decrease in liver inflammation and senescence, lower ileum CD4+/CD8+ T cells and higher liver CD14+ cells (p<0.05). Concomitantly, the metabolic disturbances in our diet-induced NASH model were normalized by NKA/Src signaling blockage and exercise with a paucity of apoptotic activity, mitigation of cell senescence, and regression of liver fibrosis (p<0.01). CONCLUSIONS. pSrc inhibition at caveolar α1-Na/K-ATPase rescinded NASH-related metabolic disturbances establishing resident physiological microbiota communities with concomitant paucity on apoptotic activity and regression of liver fibrosis; effects that were associated with both gut and liver T-lymphocyte responses.

Background: Health policy is a set of comprehensive principles and legislations that guide how healthcare should be effectively delivered in the community. Medical schools should prepare students to undertake managerial responsibilities by incorporating health policy in the curriculum to deal with the intricacies of healthcare systems and their clinical roles in their future professional careers. Objective: To examine medical students' perception at a Public University in Malaysia regarding teaching health policy and their participation in health policy roles. Material and Methods: A cross-sectional study using universal sampling was carried out among the medical students using a paper-based questionnaire to collect the data. Results: Most respondents opined their willingness to learn health policy (80.9%) and that teaching health policy (83.6%) should be compulsory for medical students. The respondents thought health policy should be introduced earlier in Year 1 or 2. The student scores on their knowledge regarding health policy and year of study were significantly associated with their involvement in the health policy roles in both the simple and multiple logistic regression. Both statistical tests reported higher participation in health policy roles with the higher year of study, though only Year 4 and 5 were significant in the simple logistic regression and only Year 5 in the multiple logistic regression compared to Year 1. On the other hand, age and type of admission show significant results only in the simple logistic regression, while the race was only significant at the multivariate level. Conclusion: This study demonstrated that most respondents showed their willingness to learn health policy, participate in the health policy programs, and recommend that health policy be considered an essential topic in the medical curriculum, which should be taught right from the first year of medical school. We recommend encouraging students’ participation in health policy activities.

This was a retrospective cohort study, which aimed to investigate the factors associated with hesitancy to receive the third dose of coronavirus disease 2019 (COVID-19) vaccine. A paper-based questionnaire survey was administered to all participants. Accordingly, the study included participants who provided answer in the questionnaire whether they have an intent to receive the third dose of vaccine. Data on sex, age, area of residence, adverse reactions after the second vaccination, whether the third vaccination was desired, and reasons to accept or hesitate booster vaccination were retrieved. Among the 2439 participants with mean (±SD) age of 52.6±18.9 years, and median IgG-S antibody titer of 324.9 (AU/mL), 97.9% of participants indicated their intent to accept a third vaccination dose. The logistic regression revealed that younger age (OR=0.98; 95% CI: 0.96-1.00) and higher antibody level (OR=2.52; 95% CI: 1.27-4.99) are positively associated with the third vaccine hesitancy. The efficacy of the COVID-19 vaccine and concerns about adverse reactions had significant impact on the third vaccination behavior. A rapid increase in the booster dose rate is needed to control the pandemic, and specific approaches should be taken in these groups that are likely to hesitate the third vaccine, subsequently increasing booster contact rate.

Development of supervised AI algorithms requires a large amount of labeled images. Image labelling is both time-consuming and expensive. Therefore, we explored the value of e-learning derived annotations for AI algorithm development in medical imaging. Methods We have developed an e-learning platform that involves image-based single click labelling as part of the educational learning process. Ten radiology residents, as part of their residency training, trained the recognition of pneumothorax on 1161 chest X-rays in posterior-anterior projection. Using this data, multiple AI algorithms for detecting pneumothorax were developed. Classification and localization performance of the models was tested on an independent internal testing dataset and on the public NIH ChestX-ray14 dataset. Results The AI models F1 scores on the internal and the NIH dataset were 0.87 and 0.44, respectively. Sensitivity was 0.85 and 0.80 for classification and specificity 0.96 and 0.48 for classification. F1 scores were 0.72 and 0.66, sensitivity 0.72 and 0.72. False positive rate was 0.36 and 0.32 for localisation. Conclusion Our results demonstrated that e-learning derived annotations are a valuable data source for algorithm development. Further work is needed to include additional parameters such as user performance, consensus of diagnosis, and quality control in the development pipeline.

Several types of soft tissue sarcomas have peripheral infiltrative growth characteristics called tail-like lesions. The efficacy of neoadjuvant therapy for tumors with tail-like lesions has not been elucidated. From 2012 to 2019, we analyzed 36 patients with soft tissue sarcoma with tail-like lesions treated with neoadjuvant therapy, including chemotherapy, radiotherapy, or both. The ef-fect of neoadjuvant therapy on the tail sign was investigated by analyzing the change in tail-like lesions during neoadjuvant therapy and histological responses. The median length of the tail-like lesion reduced from 29.5 mm at initiation to 19.5 mm after neoadjuvant therapy. The extent of shrinkage in tail-like lesion was related to the histopathological responses in the main part. Com-plete disappearance of the tail-like lesion was observed in 12 patients; however, it was not related to achieving a microscopically negative margin. The oncologic outcomes did not significantly differ between cases with complete disappearance of tail-like lesions or not. This study indicated the shrinkage of tail-like lesions did not have significant effect on complete resection or improve-ment of clinical outcomes. A more comprehensive evaluation is needed to elaborate on the surgi-cal strategy.

We performed a comprehensive analysis of angiosarcoma (AS) genomic biomarkers and their associations with the site of origin. We aimed to describe the genomic landscape of AS in a cohort of 143 cases of AS profiled by Caris Life Sciences. Data of Next Generation Sequencing (NGS) with a 592 gene panel was available for the entire cohort. Fifty-three cases had data of Whole Exome Sequencing (WES) which we used to study the microenvironment phenotype. Immuno-therapy (IO) response biomarkers: Tumor Mutation Burden (TMB), Microsatellite Instability (MSI) and PD-L1 status were included. IO-response markers were present in 36.4% of the cohort and in 65% of head and neck AS (H/N-AS) (p<0.0001). H/N-AS cases had predominantly muta-tions in TP53 (50.0%, p=0.0004), POT1 (40.5%, p<0.0001) and ARID1A (33.3%, p=0.5875). In breast AS, leading alterations were MYC amplification (63.3%, p<0.0001), HRAS (16.1%, p=0.0377), and PI3KCA (16.1%, p=0.2352). A microenvironment with a high immune signature, associated with better response to IO, was present in 13% of the cases. This signature was evenly distributed among different primary sites. We found that the molecular biology for AS varies significantly according to the primary site. Our findings can facilitate the design and optimiza-tion of therapeutic strategies for AS to overcome resistance to IO and targeted therapies.

Phytonutrients are plant foods that contain many natural bioactive compounds, called phytochemicals, which expose specific biological activities. These phytonutrients and their phytochemicals may play an important role in health care maintaining normal organism functions (as preventives) and fighting against diseases (as therapeutics). Phytonutrient’s components are the primary metabolites (i.e., proteins, carbohydrates, and lipids) and phytochemicals or secondary metabolites (i.e., phenolics, alkaloids, organosulfides, and terpenes). For years, several phytonutrients and their phytochemicals have demonstrated specific pharmacological and therapeutic effects in human health such as anticancer, antioxidant, antiviral, anti-inflammatory, antibacterial, antifungal, and immune response. This review summarizes the effects of the most studied or the most popular phytonutrients (i.e., turmeric, garlic, cinnamon, graviola, and oregano), and any contraindication found. This article also calculated the physicochemical properties of the main phytochemicals in the selected phytonutrients using Lipinski’s, Veber’s and Ghose’s rules. Based on our revisions for this article, all these phytonutrients have consistently shown several in vitro, in vivo, and clinical studies with great potential as preventives and therapeutics on many diseases.

Reliable evapotranspiration (ET) estimation is a key factor for water resources planning, attaining sustainable water resources use, irrigation water management, and water regulation. During the past few decades, researchers have developed a variety of remote sensing techniques to estimate ET. The Earth Engine Evapotranspiration Flux (EEFlux) application uses Landsat imagery archives on the Google Earth Engine platform to calculate the daily evapotranspiration at the local field scale (30 m). Automatically calibrated for each Landsat image, the EEFlux application design is based on the widely vetted Mapping Evapotranspiration at high Resolution with Internalized Calibration (METRIC) model and produces ET estimation maps for any Landsat 5, 7 or 8 scene in a matter of seconds. In this research we evaluate the consistency and accuracy of EEFlux products that are produced when standard US and global assets are used. Processed METRIC products for 58 scenes distributed around the western and central United States were used as the baseline for comparison. The goal of this paper is to compare the results from EEFlux with the standard METRIC applications to illustrate the utility of the EEFlux products as they currently stand. Given that EEFlux is derived from METRIC, differences are expected to occur due to differing calibration methods (automatic versus manual) and differing input datasets. The products compared include the fraction of reference ET (ETrF), actual ET (ETa), and surface energy balance components net radiation (Rn), ground heat flux (G), and sensible heat flux (H), as well as Ts, albedo and NDVI. The product comparisons show that the intermediate products of Ts, Albedo, and NDVI, and also Rn have similar values and behavior for both EEFlux and METRIC. Larger differences were found for H and G. Despite the more significant differences in H and G, results show that EEFlux is able to calculate ETrF and ETa values comparable to the values from trained expert METRIC users for agricultural areas. For non-agricultural areas such as semi-arid rangeland and forests, the automated EEFlux calibration algorithm needs to be improved in order to be able to reproduce ETrF and ETa that is similar to the manually calibrated METRIC products.

Objective: We determined, in stable ambulatory heart failure with preserved ejection fraction (HFpEF) subjects and matched controls, the capability of a novel blood based cardiac-specific cBIN1 Score (CS) to diagnose heart failure and prognosticate future hospitalization. Background: Heart failure (HF) poses a costly health care burden worldwide with rising prevalence. Abnormal calcium signaling is intrinsic to HF pathophysiology and correlates with reduced expression of a cardiac membrane scaffolding protein, cardiac bridging integrator 1 (cBIN1). We hypothesize that CS, a numerical score derived from plasma cBIN1 concentration, is a diagnostic and prognostic biomarker of HF. Methods: Plasma cBIN1 is quantified by an ELISA test, and CS is calculated as the natural log of the normalized reciprocal of plasma cBIN1 concentration. We determined CS among 52 clinically stable individuals with HFpEF (LVEF ≥ 50%) (mean age 57 ± 15 years old, 63% men) and 104 age and 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 one year longitudinal clinical information were obtained through electronic medical records. Results: Median CS is 0 (IQR -0.4 – 0.6) in the control cohort and is increased to 1.8 in the HFpEF cohort (IQR 1.5 – 2.3, p < 0.0001). For HFpEF diagnosis, CS has a receiver operating characteristic (ROC) area under the curve (AUC) of 0.94 (95% CI 0.95 – 0.99) and NT-proBNP of 0.89 (95% CI 0.83 – 0.95). Kaplan-Meier analysis of one year cardiovascular hospitalizations reveals that HFpEF patients with CS ≥ 1.8 have a hazard ratio (HR) of 4.0 (95% CI 1.4 – 11.2, p=0.009). Combining CS ≥ 1.8 with NT-proBNP ≥ 300 pg/mL, increases HR to 21.4 (95% CI 2.7 – 171.6, p=0.004). Conclusions: In a cohort of stable ambulatory HF patients with cardiomyopathies of multiple etiologies and preserved ejection fraction, a positive CS correlates with worsening myocardial health and predicts future hospitalization. CS, a marker of cardiac muscle health, provides a novel index to informing the management of stable ambulatory HF patients.

This paper presents a novel CNN-based architecture, referred to as Q-Net, to learn local feature descriptors that are useful for matching image patches from two different spectral bands. Given correctly matched and non-matching cross-spectral image pairs, a quadruplet network is trained to map input image patches to a common Euclidean space, regardless of the input spectral band. Our approach is inspired by the recent success of triplet networks in the visible spectrum, but adapted for cross-spectral scenarios, where for each matching pair there are always two possible non-matching patches; one for each spectrum. Experimental evaluations on a public cross-spectral VIS-NIR dataset shows that the proposed approach improves the state-of-the-art. Moreover, the proposed technique can also be used in mono-spectral settings, obtaining a similar performance to triplet network descriptors, but requiring less training data.

The next future using machine tools will be dominated by highly flexible and interconnected systems, in order to achieve the required productivity, accuracy and reliability. Nowadays, distortion and vibration problems are easily solved for the most common cases by sing models based on equations describing the physical laws dominating the machining process; however additional efforts are needed to overcome the gap between scientific research and the real manufacturing problems. In fact, there is an increasing interest in developing simulation packages based on “deep knowledge and models” that aid the machine designer, the production engineer, or machinists to get the best of their machines. This article proposes a systematic methodology to reduce problems in machining by means of a simulation utility, which recognizes, collects and uses the main variables of the system/process as input data, and generates objective results that help in the proper decision-making. Direct benefits by such an application are found in a) the fixture/clamping optimal design, b) the machine tool configuration, c) the definition of chatter free optimum cutting conditions and the right programming of cutting tool path at the Computer Aided Manufacturing (CAM) stage. The information and knowledge-based approach showed successful results in several local manufacturing companies.

Indian tobacco farm laborers are primarily women and children working for very low wages. The aim of this study was to explore occupational and reproductive health challenges faced by women tobacco farm labors in Mysore District, India. We conducted interview and six focus group discussions among 41 women tobacco farm laborers. Codes and themes were generated based on deductive and inductive approaches using the socio-ecological model. Participants reported symptoms of green tobacco sickness including headaches, back pain, gastric problems, weakness, and allergies during menstruation, pre-natal, and post-natal periods. Participants had poor awareness about the health effects of tobacco farming and there were gender inequalities in wages and use of personal protective equipment. Participants received support from family and commu-nity health workers during their pregnancy and post-natal period. Women reported wanting ma-ternity benefits from the tobacco board, monetary support, and nutritional supplements. There is a need for health education about the environmental dangers of tobacco among farm laborers, and more supportive policies for women farmworkers during pregnancy and post-natal periods.

Previous studies showed that some lamellarin-resembling annelated azaheterocyclic carbaldehydes and related imino adducts, sharing the 1-phenyl-5,6-dihydropyrrolo[2,1-a]isoquinoline (1-Ph-DHPIQ) scaffold, are cytotoxic in tumor cells and may reverse multidrug resistance (MDR) mediated by P-glycoprotein (P-gp). Herein, we synthesized and evaluated for their antiproliferative activity in four tumor cell lines (RD, HCT116, HeLa, A549) and ability of inhibiting P-gp-mediated MDR some ten diversely substituted 1-Ph-DHPIQ derivatives bearing at position 2 carboxylate groups (COOH, COOEt), nitriles (CN) and Mannich bases (e.g., morpholinomethyl derivatives). Lipophilicity parametrization and molecular docking calculations improved the understanding of the structure-activity relationships in cytotoxicity and P-gp inhibition of the investigated 1-Ph-DHPIQs, which led us to disclose a novel Mannich base HCl salt (8b’), which proved to be cytotoxic to all the tested tumor cell lines in the low micromolar range (IC50 &lt; 20 M) and to inhibit in-vitro the efflux pumps P-gp and MRP1 responsible for MDR, with IC50s of 0.45 and 12.1 M, respectively.

Toxoplasmosis is a zoonosis of warm-blooded animals, affecting also humans, caused by Toxo-plasma gondii, an obligate intracellular parasite with a complex biological cycle. Toxoplasmosis is considered a re-emerging zoonosis and an important public health threat, also for the absence, up to now, of efficient vaccines and preventive measures. Sources of transmission to humans are environmental or food-borne, mainly through the consumption of raw and undercooked meat, predominantly of Sus scrofa, considered highly susceptible to T. gondii. Mainly in the last dec-ades, an effective strategy to counter animal infectious diseases was based on the discovery of resistance immuno-genetic markers, possibly to be used for association studies between geno-typic and phenotypic traits and consequently in Marker Assisted Selection. Until now, this gen-otyping approach has never been adopted for T. gondii infection, so this study aimed, for the first time, to fill this gap. In particular, pigs, reared in different farms of Central Italy, were serologically characterized by an ELISA assay performed on diaphragm meat juice. Out of 179 tested animals, 98 resulted seropositive (54.74%), 57 seronegative (31.84%) and 24 doubtful (10.6%), underlining a possible re-emerging diffusion of this protozoan in the investigated areas. Atten-tion was firstly focused on IL-18 gene, encoding for a pro-inflammatory cytokine that plays a key role starting from the upstream steps of the immunity pathway towards T. gondii. A RT-PCR assay followed by Sanger sequencing of IL-18 cDNA was de novo developed. For this interleukin, at this stage, genetic analysis has not highlighted significant polymorphic variations compared to the reference sequence, except for a seropositive animal. However, the outcomes of this pre-liminary innovative study will be investigated in depth analyzing other relevant genetic re-gions and other target genes.

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.

Within microeukaryotes, genetic and functional variation sometimes accumulate more quickly than morphological differences. To understand the evolutionary history and ecology of such lineages, it is key to examine diversity at multiple levels of organization. In the dinoflagellate family Symbiodiniaceae, which can form endosymbioses with cnidarians (e.g., corals, octocorals, sea anemones, jellies), other marine invertebrates (e.g., sponges, molluscs, flatworms), and protists (e.g., foraminifera), molecular data have been used extensively over the past three decades to describe phenotypes and to make evolutionary and ecological inferences. Despite advances in Symbiodiniaceae genomics, a lack of consensus among researchers with respect to interpreting genetic data has slowed progress in the field and acted as a barrier to reconciling observations. Here, we identify key challenges regarding the assessment and interpretation of Symbiodiniaceae genetic diversity across three levels: species, populations, and communities. We summarize areas of agreement and highlight techniques and approaches that are broadly accepted. In areas where debate remains, we identify unresolved issues and discuss technologies and approaches that can help to fill knowledge gaps related to genetic and phenotypic diversity. We also discuss ways to stimulate progress, in particular by fostering a more inclusive and collaborative research community. We hope that this perspective will inspire and accelerate coral reef science by serving as a resource to those designing experiments, publishing research, and applying for funding related to Symbiodiniaceae and their symbiotic partnerships.

Population-based data on hematologic malignancies (HM) are rare in Greece regarding adults (≥18 years old). The aim of this study was the assessment of the burden of these malignant neoplasms (MN) for adults in Crete. The study assessed temporal trends of incidence and mortality, depicted their spatial distribution and extracted net-survival curves of patients. Population-data on these MN were obtained from the database of the Cancer Registry of Crete, for a 22 year time period (1/1/1992-31/12/2013). All HM were classified into four main groups of diseases: (1) Hodgkin’s lymphoma (HL); (2) Non-Hodgkin’s lymphomas (NHLs); (3) Multiple myeloma (MM); and (4) All chronic and acute leukemias. Annual, gender-specific, age standardized incidence and mortality rates were estimated (ASIR/100.000/year; ASMR/100.000/year). A total of 3,380 newly diagnosed cases were included in the final analyses; All ASIRs/100,000 increased significantly throughout the study period presenting differences in their geographical distribution of rates among municipalities of Crete. ASIRs for NHLs, HL, MM, leukemias and for all 4 MN were 13.1, 2.6, 4.7, 11.7 and 32.1, respectively, in 2013. Five-year net-survival for patients diagnosed with NHLs, HL, MM and leukemias were: 82%, 85%, 52% and 56%, respectively. This first research article studying a long period of time for adults in Greece generates hypotheses on the existence of risk factors that may partly explain this variation of rates.

Behavior analysis is a widely used non-invasive tool in the practical production routine, as the animal acts as a biosensor capable of reflecting its degree of adaptation and discomfort to some environmental challenge. Predominantly, conventional statistics use occurrence data for behavioral evaluation and well-being estimation, disregarding the temporal sequence of events. The Generalized Sequential Pattern (GSP) algorithm is a data mining method that identifies recurrent sequences that exceed a user-specified support threshold, whose potential has not yet been investigated for broiler chickens in enriched environments. Enrichment aims to increase environmental complexity with promising effects on animal welfare, stimulating priority behaviors and potentially reducing the deleterious effects of heat stress. The objective was to validate the application of the GSP algorithm to identify temporal correlations between heat stress and the behavior of broiler chickens in enriched environments through proof of concept. Video image collection was carried out automatically for 48 continuous hours, analyzing a continuous period of seven hours, from 12:00 PM to 6:00 PM, during two consecutive days of tests for chickens housed in enriched and non-enriched environments under comfort and stress temperatures. Chickens at comfort temperature showed high motivation to perform the behaviors of Preening (P), Foraging (F), Lying down (Ld), Eating (E), and Walking (W) whose sequences &lt;{Ld,P}&gt;; &lt;{Ld,F}&gt;; &lt;{P,F,P}&gt;; &lt;{Ld,P,F}&gt; and &lt;{E,W,F}&gt; were the only ones observed in both treatments. All other sequential patterns (comfort and stress) were distinct, suggesting that environmental enrichment alters the behavioral pattern of broiler chickens. Heat stress drastically reduced the sequential patterns found at the 20% threshold level in the tested environments. The behavior of lying laterally "Ll" is a strong indicator of heat stress in broilers and was only frequent in the non-enriched environment, which may suggest that environmental enrichment provides the animal with better opportunities to adapt to stress-inducing challenges, such as heat.

Manuka honey (MH) exhibits potential antitumor activity in preclinical models of a number of human cancers. Treatment in vitro with MH at concentrations ranging from 0.3-5.0% (w/v) led to significant dose-dependent inhibition of proliferation of human breast cancer MCF-7 cells, but anti-proliferative effects of MH were less pronounced in triple-negative MDA-MB-231 breast cancer cells. Effects of MH were also tested on non-malignant human mammary epithelial cells (HMEC) at 2.5% w/v, and it was found that MH reduced proliferation of MCF-7 cells but not that of HMEC. Notably, the antitumor activity of MH was in the range of that exerted by treatment of MCF-7 cells with the antiestrogen tamoxifen. Further, MH treatment stimulated apoptosis of MCF-7 cells in vitro, with most cells exhibiting acute and significant levels of apoptosis that correlated with PARP activation. Additionally, effects of MH induced activation of AMPK and inhibition of AKT/mTOR downstream signaling. Treatment of MCF7 cells with increased concentrations of MH induced AMPK phosphorylation in a dose dependent manner that was accompanied by inhibition of phosphorylation of AKT and mTOR downstream effector protein S6. In addition, MH reduced phosphorylated STAT3 levels in vitro which may correlate with MH and AMPK-mediated anti-inflammatory properties. Further, in vivo, MH administered alone significantly inhibited the growth of established MCF-7 tumors in nude mice by 84%, resulting in an observable reduction in tumor volume. Our findings highlight the need for further research into the use of natural compounds, such as MH, for antitumor efficacy and potential chemoprevention and investigation of molecular pathways underlying these actions.

MicroRNAs (miRNAs) play important roles in the control of HIV-1 infection. Here, we performed RNAseq profilings of miRNAs and mRNAs expressed in CD4+ T-lymphocytes upon HIV-1 infection. Our results reveal significant alterations of miRNAs and mRNAs expression profiles in infected relative to uninfected cells. One of the miRNAs markedly downregulated in infected cells is miRNA-26a. Among the putative targets of miRNA-26a are CD59 receptor transcripts, which are significantly upregulated in infected CD4+ T-cells. Addition of miRNA-26a mimics to CD4+ T-cells reduces CD59 at both mRNA and surface protein levels, validating CD59 as a miRNA-26a target. Consistent with the reported inhibitory role of CD59 in complement-mediated lysis (CML), knocking-out CD59 in CD4+ T-cells renders both HIV-1 infected cells and progeny virions more prone to antibody-dependent CML (ADCML). Addition of miRNA-26a mimics to infected cells leads to enhanced sensitivity of progeny virions to ADCML, a condition linked to a reduction of CD59 packaging into released virions. Lastly, HIV-1-mediated downregulation of miRNA-26a expression is shown to be dependent on integrated HIV-1 expression but does not involve viral accessory proteins. Overall, these results highlight a novel mechanism by which HIV-1 limits ADCML by upregulating CD59 expression via miRNA-26a downmodulation.

In this pilot study, 84 subjects with a history of poor oral hygiene were enrolled in an interventional, randomized, prospective, open-label controlled trial. The aim was to provide preliminary clinical data on the products, the recruitment monthly rate, and patient satisfaction to estimate resources for the main study, as well as descriptive data on oral microbiota rebalancing. The population was divided into five groups: 20 participants received delicate mint toothpaste, 12 mint toothpaste, 20 mint mouthwash, and 20 delicate mint toothpaste and mint mouthwash using a specifically custom-designed toothbrush. The 12 subjects in the control group continued to use their oral care products without changing their normal routine. The study duration was 28 days.All subjects tolerated the products well, and there were no adverse events. Recruitment capability and procedures allowed a realistic estimation for the future main trial. The products did not cause any changes in tooth color. The participants who completed the treatment consisting of delicate mint toothpaste, mint mouthwash, and the specifically custom-designed toothbrush showed the gingival sensitivity best results (p≤0.000). The products induced a statistically significant decrease in plaque in all treated groups (p≤0.000) and an improvement of gingival sensitivity (delicate mint toothpaste, p≤0.005; mint toothpaste, p≤0.015; and mint mouthwash, p≤0.015). All the products were effective in stabilizing the oral microbiota.The tested products showed an optimal safety profile. They also stabilized the biodiversity of the oral microbiota, making it less susceptible to microbial fluctuations than the control group.

Stress during a pandemic increased the risk of alcohol consumption, which may require pharmacological management. The characteristics of emergency calls for alcohol-related issues for patients pharmacologically treated, admitted to, or not admitted to the emergency department (ED) were analyzed. An observational single-center retrospective study was conducted from January 1, 2018 to December 31, 2021, and divided into 2-year periods (2018–2019 and 2020–2021). This study focused on calls to one of the EDs of seven hospitals in the Bari (Italy) metropolitan area for patients requiring emergency services (ES) who were either admitted or not admitted, due to their refusal. A 30% reduction in emergency calls for alcohol-related issues and a 41.17% reduction in calls for patients who refused to be admitted to the ED were observed during the pandemic. During the pandemic, a reduced rate of pharmacological treatment for calls coded green (non-critical), and an increase in calls coded yellow (fairly critical) and red (very critical) were recorded. Metadoxine was administered in almost all alcohol-related emergencies, primarily in conjunction with drugs acting on the gastrointestinal tract, irrespective of age, the period considered, and whether patients were admitted or not admitted to the ED. ES is the first and only out-of-hospital service encountered by numerous patients with alcohol-use disorders who refuse to be admitted to the ED. These patients should be directed by ES personnel to a multidisciplinary program to receive treatment for drinking, improve their quality of life, and reduce sanitation costs.

Major cardiovascular events (MACE) are a cause of major mortality worldwide. The narrowing and blockage of coronary arteries with atherosclerotic plaques is diagnosed and treated with percutaneous coronary intervention (PCI). During this procedure, coronary angiography (CAG) remains the most widely used guidance modality for the evaluation the affected blood vessel diameter in order to decide if intervention with stent colocation is suitable, where small blood vessels (&lt; 2.75 mm) are majorly left untreated; however, small vessel coronary artery disease (SvCAD) is a significant risk factor for recurrence of MACE, and there are some limitations to the use of CAG that could be improved with the use of newer techniques such as intravascular ultrasound (IVUS), although at higher costs, which might explain their underuse. To address this discrepancy and identify specific cases for its use, we conducted a retrospective study in patients who underwent PCI for MACE with at least one small blood vessel affected. The affected small blood vessels’ diameter was obtained with both CAG and IVUS, additionally we underwent a multivariate analysis to identify risk factors associated with a change in diameter. We included information from 48 patients with mean + SD age of 69.1 + 11.9 years and 34% were masculine gender. We found a significant positive low correlation in diameter measurements of small blood vessels (r=0.1242 p=0.014). Mean diameter with CAG and IVUS was 2.1 mm (95% CI 1.9-2.2), and 2.8 (2.8-3.0) the estimated difference was of 0.8 mm (95 % CI 0.7-0.9). In total 37 (77%) of patients had a reclassification of their blood vessels from a small to medium (2.75-3.00 mm) in 21 cases, or even large (&lt;3.00 mm) in 15 cases, after IVUS; this was important for the decision of intervention and stent collocation. The only variable associated with reclassification of blood vessels after adjusted in a multivariate analysis was DT2 (p=0 0.035). Our findings corroborate that blood vessels might appear smaller with CAG, especially in the diabetes population, therefore at least in these cases the use of IVUS is recommended over CAG.

Objective: The influence of gender on the number and pattern of co-morbid psychiatric illness was archivally compared between patients with and without an Alcohol Use Disorder (AUD) among psychiatrically treated individuals drawn from a large Danish birth cohort. Method: By age 45, fifteen percent of the Copenhagen Perinatal Birth Cohort (N=8,109) had been treated in a Danish psychiatric facility. Of those 1,247 patients, 368 were assigned an AUD diagnosis (29.5%). All psychiatric diagnoses assigned to these patients, over all admissions, were classified into one of 14 broad ICD-10 F categories for comparative purposes. Results: More of the patients with an AUD diagnosis were male. Patients with an AUD diagnosis were significantly more likely to receive two or more non-AUD psychiatric diagnoses than patients without an AUD diagnosis. The number of psychiatric diagnoses was greater for female than male AUD patients, a difference not found among male and female patients without an AUD diagnosis. For patients with no AUD diagnosis, the influence of gender on the pattern of psychiatric disorders was similar to that commonly reported. In contrast, the influence of gender on the number and pattern of psychiatric disorders for patients with an AUD diagnosis indicated fewer gender differences. Several diagnostic categories that discriminated male from female patients without an AUD-related diagnosis, no longer discriminated male from female patients with an AUD-related diagnosis. Conclusions: Our findings suggest that gender differences associated with psychiatric comorbidity that have been reported in large heterogenous study, should not be generalized to specific diagnostic groups without further study.

Tinnitus is a common phantom auditory percept, believed to be related to plastic changes in the brain due to hearing loss. However, tinnitus can also occur in absence of any clinical hearing loss. Then, since there is no hearing loss, the mechanisms that drive plastic changes remain largely enigmatic. Previous studies showed subtle differences in sound-evoked brain activity associated with tinnitus in subjects with tinnitus and otherwise, normal hearing, but the results are not consistent across studies. Here, we aim to investigate those differences using monaural rather than binaural stimuli. Sound-evoked responses were measured using functional magnetic resonance imaging (MRI) in participants with and without tinnitus. All participants had clinically normal audiograms. The stimuli were pure tones with frequencies between 353 and 8000 Hz, presented monaurally. A Principal Component Analysis (PCA) of the response in the auditory cortex revealed no difference in tonotopic organization, which confirmed earlier studies. A GLM analysis showed hyperactivity in the lateral areas of the bilateral auditory cortex. Consistent with the tonotopic map, this hyperactivity mainly occurred in response to low stimulus frequencies. This may be related to hyperacusis, which was associated with tinnitus found in the parahippocampus. This may reflect an interference between tinnitus and spatial orientation.

We report neutralization titer data against contemporary SARS-CoV-2 sublineages from an ongoing, open-label, phase 2/3 trial of a single 30-μg dose of monovalent Omicron XBB.1.5-adapted BNT162b2 vaccine. Healthy participants had previously received ≥3 doses of a US-authorized mRNA vaccine, with the most recent being a bivalent Omicron BA.4/BA.5-adapted vaccine administered ≥150 days before study vaccination. In this analysis, Omicron XBB.1.5, BA.2.86, and JN.1 serum neutralizing titers were assessed at baseline and 1 month after vaccination in a subset of ≥18-year-olds (N = 40) with evidence of previous SARS-CoV-2 infection. Immunogenicity was also evaluated in a demographically matched group of participants who received bivalent BA.4/BA.5-adapted BNT162b2 in another study (ClinicalTrials.gov Identifier: NCT05472038). The XBB.1.5-adapted BNT162b2 vaccine elicited higher XBB.1.5, BA.2.86, and JN.1 neutralizing titers than those elicited by bivalent BA.4/BA.5-adapted BNT162b2. Overall geometric mean fold rises in neutralizing titers from baseline to 1 month after vaccination were higher among participants who received XBB.1.5-adapted BNT162b2 than those who received bivalent BA.4/BA.5-adapted BNT162b2 for XBB.1.5 (7.6 vs 5.6), slightly higher for JN.1 (3.9 vs 3.5), and similar for BA.2.86 (4.8 vs 4.9). ClinicalTrials.gov Identifier: NCT05997290.

Programmed death ligand 1 (PD-L1) is a co-inhibitory molecule expressed on the surface of various cell types, known for its suppressive effect on T cells through interaction with PD-1. Neutrophils also express PD-L1, and its expression is elevated in specific situations; however, the immunobiological role of PD-L1+ neutrophil has not been fully characterized. Here, we report that PD-L1-expressing neutrophils increased in methicillin-resistant Staphylococcus aureus (MRSA) infection are highly functional in bacterial elimination and supporting inflammatory resolution. The frequency of PD-L1+ neutrophils was dramatically increased in MRSA-infected mice, and this population exhibited enhanced activity in bacterial elimination compared to PD-L1- neutrophils. An administration of PD-L1 monoclonal antibody did not impair PD-L1+ neutrophil function suggesting that PD-L1 expression itself does not influence neutrophil activity. However, PD-1/PD-L1 blockade significantly delayed liver inflammation resolution in MRSA-infected mice, as indicated by increased plasma alanine transaminase (ALT) level and frequencies of inflammatory leukocytes in the liver implying that neutrophil PD-L1 suppresses the inflammatory response of these cells during the acute phase of MRSA infection. Our results reveal that elevated PD-L1 expression can be a marker for enhanced anti-bacterial function of neutrophils. Moreover, PD-L1+ neutrophils are an indispensable population attenuating inflammatory leukocyte activities assisting in a smooth transition into the resolution phase in MRSA infection.

Background: The effect of COVID-19 infection, versus the indirect effect of the pandemic on body composition remains unclear. This study investigates long-term changes in body composition in COVID–19 survivors compared to a contemporary control group. Method: This is a prospective study involving adults who had a pre-pandemic whole-body DXA scan (DXA#1) performed between 2017 and 2019. Participants were asked to return for a repeat whole-body DXA scan (DXA#2) after the pandemic. Detailed data were collected including medical and COVID history. Inflammation markers and fasting lipids were measured. For those participants who had a COVID-19 infection between the 2 DXAs, DXA#2 was acquired at least one year after COVID-19 infection. Results: Overall, 160 adults were enrolled; 32.5% females, 51.8% non-white, with mean age of 43.2 years. Half (n=80) of the participants had documented COVID infection between their 2 DXA scans (COVID+ group), and the other half never had COVID. COVID-negative participants had an increase in annualized trunk fat (g) [922.5 vs. 159.7; P=0.01], total fat (g) [1564.3 vs. 199.9; P=0.2], and LBM (g) [974.9 vs. -64.5; P=0.0002], when compared to COVID+ group. However, among the COVID+ group, no differences were seen in annualized trunk fat, total fat mass, or LBM between those with PASC and without (p>0.05). Conclusion: During the pandemic, both COVID-19-survivors and COVID-negative groups exhibited increases in weight, and total and trunk fat, likely associated with pandemic-linked lifestyle modifications. However, only COVID-19-survivors had a decline in lean body mass over the same period, regardless of PASC symptoms.

ADHD is a neurodevelopmental disorder that children and also adults can develop. A complex interplay of genetic and environmental factors may underlie interindividual variability in ADHD and potentially related aggressive behavior. Using high-resolution molecular biology techniques, we investigated the impact of some MAOA and SLC6A4 variations on ADHD and aggressive behavior in a group of 80 Italian children with ADHD and in 80 healthy controls.We found that homozygous genotypes of MAOA rs6323 and rs1137070 were associated with an increased risk of ADHD (p=0.02 and p=0.03, respectively), instead the heterozygous genotypes (GT of rs6323 and CT of rs1137030) (p=0.0002 and p=0.0006) were strongly linked to a lower risk of developing this disorder. In patients with aggressive behavior, we highligted only a weak negative association of both MAOA polymorphisms (heterozygous genotypes) with aggressiveness then, suggesting that these genotypes maybe protective towards specific changes in behavior (p=0.05). Interestingly, an increase of the GG genotype of rs6323 (p=0.01) and a decrease of GT genotype (p=0.0005) was also found in patients without aggressive behavior compared with controls. Regarding 5HTT gene genotyping, no allele and genotype differences have been detected among patients and controls. Our work shows that defining a genetic profile of ADHD may help to early detect those patients who are more vulnerable to ADHD and/or antisocial and aggressive behavior and to design precision-targeted therapies.

Vaccination remains an important mitigation tool against COVID-19. We report 1-month safety and preliminary immunogenicity data from a substudy of an ongoing, open-label, phase 2/3 study of monovalent Omicron XBB.1.5-adapted BNT162b2 (single 30-μg dose). Healthy, participants ≥12 years old (N=412 [12‒17 years, N=30; 18‒55 years, N=174; >55 years, N=208]) who previously received ≥3 doses of a US-authorized mRNA vaccine, the most recent being an Omicron BA.4/BA.5-adapted bivalent vaccine ≥150 days before study vaccination, were vaccinated. Serum 50% neutralizing titers against Omicron XBB.1.5, EG.5.1, and BA.2.86 were measured 7 days and 1 month after vaccination in a subset of ≥18-year-olds (N=40) who were positive for SARS-CoV-2 at baseline. Seven-day immunogenicity was also evaluated in a matched group who received bivalent BA.4/BA.5-adapted BNT162b2 in a previous study (NCT05472038). There were no new safety signals; local reactions and systemic events were mostly mild to moderate in severity, adverse events were infrequent, and none led to study withdrawal. The XBB.1.5-adapted BNT162b2 induced numerically higher titers against Omicron XBB.1.5, EG.5.1, and BA.2.86 than BA.4/BA.5-adapted BNT162b2 at 7 days and robust neutralizing responses to all 3 sublineages at 1 month. These data support a favorable benefit-risk profile of XBB.1.5-adapted BNT162b2 30 μg. NCT05997290

The paper presents the observational, remote sensing and model simulation to analyze Southern Brazil Antarctic Ozone Hole influence (SBAOHI) events occurred between 2005 and 2014. To an-alyze it we use Total Ozone Column (TOC) data provide by Brewer Spectrophotometer (BS) and OMI (Ozone Monitoring Instrument) instrument satellite, besides the AURA/MLS (Microwave Limb Sounder) instrument satellite ozone profiles was utilized with DYBAL (Dynamical Barrier Localization) code in MIMOSA (Modélisation Isentrope du transport Mésoéchelle de l’Ozone Stratosphérique par Advection) model Potential Vorticity (PV) fields. TOC has 7.0 ± 2.9 DU re-ductions average in 62 events. October have more events (30.7%). Polar Tongue events are 19.3% of total, being in October more frequently observed (50% of cases), with medium intensity (58.2%) and in stratosphere medium levels (55.0%). Already Polar Filament events (80.7%) are more frequent in September (32.0%), medium intensity (42.0%) and in stratosphere medium lev-els (40.7%). ENSO index positive phase influenced 61.3% of events, having dominance in all in-tensity categories (minor 57.9%, medium 51.6%, major 58.3%), while the equilibrium dominate the QBO influence with 50% of total cases in positive phase and 50 % in negative phase.

Objective: To identify risk factors(RF) related to abnormal glucose regulation(AGR) 3 years postpartum according to 3-month-postpartum glucose status. Research design: Normoglycemic pregnant women of the St. Carlos Gestational Study included before gestational week 12, during 2015-2017. Of 3,036 eligible women, 2529 were followed-up until delivery: 1400 participated in postpartum follow-up. AGR defined as fasting serum glucose (FSG)>5.6 mmol/L and/or HbA1c >5.7% (39 mmol/mol) and/or 2h-SG ≥140/mg/dL after 75-g OGTT. 12-modifiable and 3-unmodifiable RF were analyzed for associations with glycemic changes. Reinforcement of Mediterranean Diet adherence was provided to all women at the postpartum visit by a dietitian Results: 137/1400(9.8%) women presented AGR 3 years postpartum, 27/137(19.7%) also had at 3 months, whereas 110/137(80.2%) had not. The remaining 1,263(90.2%) women were normoglycemic 3 years postpartum, 1180/1263(84.3%) were at 3 months, while 83/1263(6.08%) had AGR and became normoglycemic. Women with GDM were more likely to progress to AGR 3 years postpartum (OR:1.60[1.33-1.92]) and less likely to remain normoglycemic (OR:0.22[0.15-0.33]) versus non-GDM women. Having >2/3 unmodifiable RF was associated with a reduced rate of maintained normoglycemia (OR:0.56[0.39-0.80]) and an increased risk of progression to AGR (OR:1.90[1.28-2.83]). Having >5/12 modifiable RF was associated with a reduced rate of maintained normoglycemic (OR:0.74[0.51-0.99]) and reversion of AGR (OR:0.49[0.25-0.97]), an increased progression to AGR (OR:1.40[1.00-2.09]), and persistence of AGR (OR:2.57[1.05-6.31]). Pre-gestational BMI≥25kg/m2 (OR:1.80[1.19-2.71]), post-delivery weight gain (OR:2.22[1.10-4.48]), and waist circumference >89.5cm (OR:0.54[0.36-0.79]), (all p<0.05) were the main modifiable RF. Conclusions: RF related to an increased probability for 3-year-postpartum AGR despite 3-month normoglycemia were identified, potentially useful when designing personalized strategies for pregnant women, directed towards minimizing unfavorable outcomes.

The antimicrobial properties of the new strains of microorganisms isolated from natural sources of various ecological niches in the Moscow Region and the Republic of Tatarstan were studied. An antifungal activity of isolates was established in a test culture of toxin-producing microscopic fungi that cause various plant diseases: Fusarium oxysporum, Aspergillus flavus, Penicillium spp. and Candida albicans. Of the 46 studied microorganisms, 4 isolates (Bacillus subtilis, Propionibacterium freudenreichii, Lactobacillus plantarum and Streptomyces spp.) showed an ability to produce biologically active metabolites with a pronounced antimicrobial potential. This is promising in the growth and protection of the Scots pine, pedunculate oak and small-leaved linden forest crops from diseases caused by fungi Lophodermium pinastri Chev. and Microsphaera alphitoides stimulation. Based on selected isolates, a Bacterial product LRV composition has been developed. A Scots pine, pedunculate oak and small-leaved linden seedlings single and double foliar treatment with Bacterial product LRV at a concentration of 10 ml/l led to an increase in the growth of an above-ground part by 31.8, 51.9 and 25.4 %, respectively, and an underground part – by 25.0, 37.2 and 25.7 %, respectively, compared with the control. The weight of seedling at the end of the study exceeded the control variant by an average of 26.0, 44.0 and 78.0 %, respectively. A use of a plant protection Bacterial product LRV did not have a significant effect on a powdery mildew and Schütte disease damage to forest crops. A Biogeosystem Technique methodology has been developed to improve a long-term forest growing.

Light enables vision and exerts widespread effects on physiology and behaviour, including regulating circadian rhythms, sleep, hormone synthesis, affective state, and cognitive processes. Appropriate lighting in animal facilities may support welfare and ensure that animals enter experiments in a controlled physiological and behavioural state. Proper consideration of light during experimentation - both when it is explicitly employed as an independent variable and as a general feature of the environment - has the potential to provide more informative experimental designs and more reliable outcomes, contributing to Reduction and Refinement, helping to ensure more ethical animal use, and improving data quality. As such, it is unfortunate that ambient light for animals is typically quantified in units (lux) designed for human observers. We report the consensus views of an expert working group, with expertise spanning mammalian photobiology, neurobiology and animal husbandry and welfare, convened in February 2023 to agree upon metrics for light appropriate for non-human mammals and their application to improve animal welfare and the quality of animal research. We conclude that species-specific versions of the recently standardised a-opic metrology represent the best available approach to quantifying light. We provide methods for measuring these quantities; practical guidance for their implementation in husbandry and experimentation; and quantitative guidance on appropriate light exposure for laboratory mammals.

Vascular calcification (VC), is a common complication in patients with chronic kidney disease and increases mortality. Although oxidative stress is involved in the onset and progression of this disorder, the specific role of some main redox regulators such as catalase, the main scavenger of H2O2, remains unclear. In the present study, epigastric arteries of kidney transplant recipients, an in vivo model of VC and an in vitro model of VC exhibiting catalase overexpression (Cts) were analyzed. Peri-calcification areas of human epigastric arteries have increased levels of catalase and cytoplasmic rather than nuclear RUNX2. In the in vivo model, advanced aortic VC concurs with lower levels of the H2O2 scavenger, glutathione peroxidase 3 compared to controls. In an early model of calcification using vascular smooth muscle cells (VSMCs), Cts VSMCs showed the expected increase in RUNX2 total levels. However, Cts VMSC also exhibited lower percentage of the nucleus stained for RUNX2 in response to calcifying media. At this early model of VC we did not observe dysregulation of mitochondrial redox state, an increase in general redox state was observed in the cytoplasm. These in vivo and in vitro results highlight the complex role of antioxidant enzymes as catalase in the process of VC by regulation of RUNX2 location.

Introduction. Streptococcus pneumoniae infections are a major cause of mortality and morbidity worldwide. In Jordan, pneumococcal conjugate vaccines (PCVs) are not included in the national vaccination program. Due to the current availability of several PCVs including PCV-10, PCV-13 and PCV-15, along with PCV-20, currently undergoing pediatric approvals globally, the decision to introduce PCVs and their selection should be based on valid local data on the common serotypes of Streptococcus pneumoniae. Methods: This cross-sectional study aimed to identify the frequency of serotypes of Streptococcus pneumoniae in children aged below 5 years hospitalized with invasive pneumococcal diseases (IPD) including pneumonia, septicemia and meningitis during the study’s duration in representative areas of Jordan. Serotyping for culture-positive cases was based on the capsular reaction test, known as the Quellung reaction. qPCR was conducted on blood samples of patients with lobar pneumonia identified via X-ray or on cerebrospinal fluid for those with a positive latex agglutination test for Streptococcus pneumoniae. Results. This study was based on the analysis of the serotypes of 1015 Streptococcus pneumoniae cases among children younger than the age of 5; 1006 cases with pneumonia, 6 cases with meningitis, and 3 cases with septicemia. Only 23 culture-positive cases were identified, in comparison to 992 lobar pneumonia cases which were PCR-positive but culture-negative, with a PCR positivity rate of 92%. Serotypes 6B, 6A, 14 and 19F were the most common serotypes identified in the study, with prevalence rates of 16.45%, 13.60%, 12.12% and 8.18%, respectively. PCV-10, PCV-13, PCV-15 and PCV-20 coverage rates were 45.32%, 61.87%, 64.14% and 68.47%, respectively. Discussion: To the best of our knowledge, this is largest prospective study from the Middle East and one of the largest studies worldwide showing the serotypes of Streptococcus pneumoniae. It reveals the urgency for the introduction of PCV vaccination in Jordan, utilizing recently developed vaccines with broader serotype coverage.

Bifidobacterium are a beneficial and dominant member of the breast-fed infant gut microbiome. However, the health benefits of Bifidobacterium are partially species dependent. Here we characterize the species and subspecies of Bifidobacterium present in breastfed infants around the world. Across populations, three distinct patterns of Bifidobacterium colonization emerged: 1) Dominance of Bifidobacterium longum subspecies infantis, 2) Prevalent Bifidobacterium of multiple species, and 3) Frequent absence of Bifidobacterium. These patterns appear related to country history of breastfeeding, with infants in countries with historically high rates of long duration breastfeeding more likely to be colonized by B. longum subspecies infantis compared with infants in countries with histories of shorter duration breastfeeding. These findings highlight the need to consider historical and cultural influences on gut commensal survival influence present day colonization patterns in order to understand epidemiological transmission patterns of Bifidobacterium and other major gut commensals.

Using low-cost portable air quality (AQ) monitoring devices is a growing trend in personal exposure studies enabling a higher spatio-temporal resolution and identifying acute exposure to high concentrations. Comprehension of results by participants is not guaranteed in exposure studies. However, information on personal exposure is multiplex, which calls for participant involvement in information design to maximise communication output and comprehension. This study describes and proposes a model of a user centred design (UCD) approach for preparing a final report for participants involved in a multi-sensor personal exposure monitoring study performed in seven cities within the EU Horizon 2020 ICARUS project. Using a combination of human-centred design (HCD), human-information interaction (HII) and design thinking approaches, we iteratively included participants in the framing and design of the final report. User needs were mapped using a survey (n=82), and feedback on the draft report was obtained from a focus group (n=5). User requirements were assessed and validated using a post-campaign survey (n=31). The UCD research was conducted amongst participants in Ljubljana, Slovenia and the results report was distributed among the participating cities across Europe. The feedback received made it clear that the final report was well-received and helped participants better understand the influence of individual behaviours on personal exposure to air pollution.

Detection of pancreatic cancer (PC) at a resectable stage is still difficult because of the lack of accurate detection tests. The development of accurate biomarkers in low or non-invasive biofluids is essential to enable frequent tests, which would help increase the opportunity of PC detection in early stages. Polyamines have been reported as possible biomarkers in urine and saliva samples in various cancers. Here, we analyzed salivary metabolites, including polyamines, using capillary electrophoresis-mass spectrometry. Salivary samples were collected from patients with PC (n=39), chronic pancreatitis (CP, n=14) and controls (C, n=26). Polyamines, such as spermine, N1-acetylspermidine, and N1-acetylspermine, showed a significant difference between PC and C, and the combination of four metabolites including N1-acetylspermidine showed high accuracy in discriminating PC from the other two groups. These data showed the potential of saliva as a screening test for PC.

Based upon Maxwell's equations, it has long been established that oscillating electromagnetic (EM) fields incident upon a metal surface decay exponentially inside the conductor, leading to a virtual EM vacuum at sufficient depths. Magnetic resonance imaging (MRI) utilizes radiofrequency (r.f.) EM fields to produce images. Here we present the first visualization of a virtual EM vacuum inside a bulk metal strip by MRI, amongst several novel findings. We uncover unexpected MRI intensity patterns arising from two orthogonal pairs of faces of a metal strip, and derive formulae for their intensity ratios, revealing differing effective elemental volumes (voxels) underneath these faces. Further, we furnish chemical shift imaging (CSI) results that discriminate different faces (surfaces) of a metal block according to their distinct nuclear magnetic resonance (NMR) chemical shifts, which holds much promise for monitoring surface chemical reactions noninvasively. Bulk metals are ubiquitous, and MRI is a premier noninvasive diagnostic tool. Combining the two, the emerging field of bulk metal MRI can be expected to grow in importance. The fundamental nature of results presented here may impact bulk metal MRI and CSI across many fields.

The enzyme acetylcholinesterase (AChE) plays a crucial role in the termination of nerve impulses by hydrolyzing the neurotransmitter acetylcholine (ACh). The inhibition of AChE has emerged as a promising therapeutic approach for the management of neurological disorders such as Lewy body dementia and Alzheimer's disease. The potential of various compounds as AChE inhibitors has been investigated. In this study, we evaluated the impact of natural compounds of interest on the intrinsic deformability of human AChE using computational biophysical analysis. Our approach incorporates classical dynamics, elastic networks, statistical potentials, energy frustration, and volumetric cavity analyses. The results revealed that cyanidin induced significant changes in the flexibility and rigidity of AChE, especially in the distribution and volume of internal cavities, compared to model inhibitors such as TZ2PA6, and through a distinct biophysical-molecular mechanism from the other inhibitors considered. These findings suggest that cyanidin could offer potential mechanistic pathways for future research and applications in the development of new treatments for neurodegenerative diseases.

Hepatitis C virus (HCV) is an oncogenic virus that causes chronic liver disease in more than 80% of patients. During the last decade, efficient direct acting antivirals were introduced into clinical practice. However, clearance of the virus does not reduce risk of end-stage liver diseases to the level observed in patients that have never been infected. So, investigation of HCV pathogenesis is still warranted. Virus-induced changes in cell metabolism contribute to the development of HCV-associated liver pathologies. Here we studied the impact of the virus on the metabolism of polyamines and proline as well as on the urea cycle, which plays a crucial role in liver function. It was found that HCV strongly suppresses the expression of arginase, a key enzyme of the urea cycle, leading to accumulation of arginine and upregulates proline oxidase with a concomitant decrease in proline concentrations. Addition of exogenous proline moderately suppressed viral replication. HCV upregulated transcription but suppressed protein levels of polyamine-metabolizing enzymes. This resulted in a decrease in polyamine content in infected cells. Finally, compounds targeting polyamine metabolism demonstrated pronounced antiviral activity pointing to spermine and spermidine as compounds affecting HCV replication. These data expand our understanding of HCV’s imprint on cell metabolism.

Objectives: Describe the epidemiology of burns in the pediatric population. Analyze and compare the results obtained from the treatment of burn wounds by using the bio-preserved human epidermis allograft (BHEA) and other types of dressings and determine the need for further need of a skin graft. Methods: A retrospective cross-sectional study of pediatric population with burn injuries was conducted, grouped into categories based on their age group, and the mechanisms of injury into 6 categories: scald, flame, contact, electrical, chemical and friction. Describing the extension and depth of the burn injury. The results of treatment of two groups; the patients who used (BHEA) and the group with “other dressings” were analyzed by inferential statistics to establish the relationship between the use of BHEA and the need for skin grafts compared to the other group. Results: A total of 65 patients were obtained. The average age was 4.5 years (±3.8). Preschoolers (1-5 years old) were the most frequent age group 64% (n=42). Male patients represented 61% (n=40) of cases. Scald was the most reported mechanism 64% (n=42). The average total body surface area burned (TBSAB) was 10.8% (± 9.2). Mixed partial thickness burn (superficial and deep) was the most common with a 55%. The head was the most affected anatomical site; 30%. The face was the most reported “special anatomical site” with a 40% (n=30). 32.2 % of the population (n=21) was treated with BHEA. The average time of epithelialization of the BHEA group was 8 days (±7.2), and their average hospital stay time was 7 days (±5.7). In the “other dressing” group, the average epithelialization time was 18 days (±13.6), and the average hospital stay time was 11 days (±12.6). Fifty percent (n=22) of the “other dressing” group required skin grafts. In the BHEA group only 19% (n=4) required skin grafts. An OR of 0.23 and CI of 95% (0.06 – 0.81) with a p value of (0.017) for the need of skin grafts after de use of BHEA was obtained. Conclusion: The epidemiological results reported are similar to those described in the literature. The use of (BHEA) proved to be a good option for the management of partial thickness burns and burns in transition, promoting timely epithelilization and avoiding deepening of the burns while reducing morbidity, hospital stay and care costs.

Primary Ciliary Dyskinesia (PCD) is a rare genetic disorder characterized by alterations in motile cilia func-tion. The diagnosis of PCD is challenging due to the lack of standardized methods in clinical practice. High-speed video microscopy analysis (HSVA) directly evaluates ciliary beat frequency (CBF) in PCD. Recently, open-source ciliary analysis software applications have shown promise in measuring CBF accurately. How-ever, there is limited knowledge about the performance of different software applications, creating a gap in understanding their comparative effectiveness in measuring CBF in PCD. We compared two open-source software applications, CiliarMove and Cilialyzer, against the manual count method. We used videos rec-orded at high-speed of nasal ciliary brush samples from PCD patients and healthy controls. All three meth-ods showed lower median CBF values in PCD patients than healthy controls. CiliarMove and Cilialyzer identified lower CBF in PCD patients, similar to the manual count. Cilialyzer, CiliarMove and manual count demonstrated statistical significance (p-value < 0.0001) in the difference of median CBF values be-tween PCD and healthy controls. These findings support the utility of open-source software-based analysis tools. Further studies are needed to validate these findings with other genetic variants and identify the op-timal software for accurate CBF measurement in PCD.

Triple negative breast cancer (TNBC) is associated with a generally poor prognosis due to its highly aggressive and metastatic nature, lack of targetable receptors, as well as the frequent development of resistance to chemotherapy. We previously reported that AU1, a small molecule developed as an inhibitor of BPTF (bromodomain PHD finger containing transcription factor), was capable of sensitizing preclinical models of triple negative breast cancer to chemotherapy, in part via the promotion of autophagy. In studies reported here, we identify an additional property of this compound, specifically that sensitization is associated with inhibition of the P-glycoprotein efflux pump. In silico molecular docking studies indicate that AU1 binds to active regions of the efflux pump, in a manner consistent with inhibition of pump function. This work identifies a novel chemical structure that can influence multidrug efflux, an established mechanism of drug resistance in triple negative breast cancer, that has not yet been successfully addressed by clinical efforts.

In an era marked by swift technological progress, the pivotal role of Artificial Intelligence (AI) is increasingly evident across various sectors, including local governments. These governmental bodies are progressively leveraging AI technologies to enhance service delivery to their communities, ranging from simple task automation to more complicated engineering endeavours. While more and more local governments are adopting AI, it is imperative to understand the functions, implications, and consequences of AI. Despite the growing importance of this domain, a significant gap persists within the scholarly discourse. This study strives to bridge this void by exploring the applications of AI technologies within the context of local government service provision and using this inquiry to generate lessons and best practices for similar smart city initiatives. Through a comprehensive grey literature review, we analysed 262 real-world AI implementations across 170 local governments worldwide. The findings underscore several key points: (a) There has been a consistent upward trajectory in the adoption of AI by local governments over the last decade; (b) Local governments from China, the US, and the UK are at the forefront of AI adoption; (c) Among local government AI technologies, Natural Language Processing and Robotic Process Automation emerge as the most prevalent ones; (d) Local governments primarily deploy AI across 28 distinct services; (e) Information management, back-office work, and transportation and traffic management are leading domains in terms of AI adoption. This study enriches the extant body of knowledge by providing an overview of existing AI applications within the sphere of local governance. It offers insights for smart city policymakers and decision-makers considering the adoption, expansion, or refinement of AI technologies in urban service provision. Additionally, it underscores the importance of using these insights to guide the successful integration and optimisation of AI in future smart city projects, ensuring they meet the evolving needs of communities.

This work aimed to develop an anionic cellulose nanofiber (CNF) bio-adsorbent from palm date tree waste and to investigate its removal efficiency against cationic methylene blue dye from contaminated water. Palm date pulp was first prepared from palm date leaves through acid hydrolysis using H2SO4, followed by hydrolysis in a basic medium using KOH, in which the process completely removed the components of hemicellulose, lignin, and silica. To obtain anionic CNF, the resulting pulp was further treated with H2SO4, followed by centrifugation. Biogel formation of the CNF suspension was promoted by sonication, where its removal efficiency of methylene blue dye was studied as a function of dye concentration, temperature, contact time, and pH value. Two equilibrium models, the Langmuir and Freundlich models were employed, and the Langmuir model was found to be consistent with the experimental data. The highest removal efficiency was obtained at 60oC and was 5mg/gm. Furthermore, several kinetic models were used to gain insight into the adsorption mechanism. The pseudo-second-order model provided an accurate description of the adsorption process, while the Elovich equation suggested a chemical reaction between methylene blue dye and CNF. The study’s findings were in agreement with the pseudo-second-order model, indicating general chemical reactions. The study indicates that CNF adsorbents derived from renewable natural waste sources such as palm date leaves can be effective in removing cationic contaminants such as methylene blue dye.

We have designed cell penetrating peptides that target the leucine zipper transcription factors ATF5, CE-BPB and CEBPD and that promote apoptotic death of a wide range of cancer cell types, but not normal cells, in vitro and in vivo. While such peptides have the potential for clinical application, their mechanisms of action are not fully understood. Here, we show that one such peptide, Dpep, compromises glucose uptake and glycolysis in a cell-context-dependent manner (in about 2/3 of cancer lines assessed). These actions are dependent on induction of tumor suppressor TXNIP (thioredoxin interacting protein) mRNA and protein. Knockdown studies show that TXNIP significantly contributes to apoptotic death in those cancer cells in which it is induced by Dpep. The metabolic actions of Dpep on glycolysis led us to explore combinations of Dpep with clinically approved drugs metformin and atovaquone that inhibit oxidative phosphorylation and that are in trials for cancer treatment. Dpep showed additive to synergistic activities in all lines tested. In summary, we find that Dpep induces TXNIP in a cell-context-dependent manner that in turn sup-presses glucose uptake and glycolysis and contributes to apoptotic death of a range of cancer cells.

Omsk hemorrhagic fever virus (OHFV) is a member of the tick-borne encephalitis virus (TBEV) complex of the Flaviviridae family. Currently, there is no data on cross-reactivity of antibodies to the NS1 proteins of OHFV and TBEV. Such data are of major interest for monitoring viral encephalitis of unknown etiology due to the increasing geographical distribution of OHFV. In this study, recombinant OHFV NS1 protein was produced using Escherichia сoli expression system and purified. The recombinant OHFV NS1 protein was recognized by specific mice immune ascetic fluids to the native OHFV NS1 protein. Western blot analysis and ELISA of recombinant NS1 proteins of OHFV and TBEV were used to study the cross-reactivity of antibodies from immune ascites fluid obtained from OHFV-infected mice and mAbs against TBEV NS1. Anti-TBEV NS1 mouse monoclonal antibodies (mAbs) have been shown not to be cross-reactive to OHFV NS1 protein. Sera from patients with confirmed tick-borne encephalitis (TBE) were examined by ELISA using recombinant OHFV NS1 and TBEV NS1 proteins as antigens. It was shown for the first time that cross-reactive antibodies to OHFV NS1 protein were not detected in the sera of TBE patients whereas the sera contained antibodies to TBEV NS1 protein.

Frass generated during the production of black soldier fly larvae is taking the interest of scientists and horticultural producers because it is a material from the biotransformation of organic waste, it has several nutrients that can be used by plants, and its recent focus on its biostimulant capacity. The thermal-composting process is a stabilization that improves physical and chemical properties of treated wastes, allowing better performance in plants compared to its fresh state. In this research, thermocomposted frass was evaluated as a germination substrate for kale seeds (Brassica olerasea). To achieve this, it was evaluated the phytotoxicity in different concentrations on the seeds, and seedlings were grown in a germination substrates mixed with 20, 40, 60, 80 and 100% of frass. The treatment with 20% frass showed the highest values of seedling height, stem diameter, number of leaves, length, and width of first true leaf and length and width of cotyledons, reduced the content of phenols and tannins antioxidants but the content of flavonoids increased compared to the control and the rest of mixtures.

Serine peptidases (SPs) of the chymotrypsin S1A subfamily are an extensive group of enzymes found in all animal organisms, including insects. Here we provide analysis of SPs in the yellow mealworm Tenebrio molitor transcriptomes and genomes datasets and profile their expression pattern at various stages of ontogeny. A total of 269 SPs were identified, including 137 with con-served catalytic triad residues, while others 125 lacking conservation were proposed as non-active serine peptidase homologs (SPHs). Seven deduced sequences exhibit a complex do-main organization with two or three peptidase units (domains), predicted both as active or non-active. The largest group of 84 SP and 102 SPH had no regulatory domains in the propep-tide, and the majority of them were expressed only in the feeding life stages, larvae and adults, presumably playing an important role in digestion. The remaining 53 SP and 23 SPH had differ-ent regulatory domains, showed constitutive or upregulated expression at eggs or/and pupae stages, participating in regulation of various physiological processes. The majority of polypep-tidases was mainly expressed at the pupal and adult stages. The data obtained expand our knowledge on SPs/SPHs and provide a foundation for further research on the functions of this gene family in T. molitor.

Considering the age of the dogs, it was expected that elderly animals would have stiffer thyroids than adults. The aim of this study was to evaluate the thyroid glands of healthy dogs using 2D shear wave elastography in order to establish qualitative and quantitative parameters of tissue stiffness in dogs of different age groups. The B-mode ultrasound and elastography findings were correlated with the weight and sex of the patients, allowing a reference range to be established for different groups of dogs. 31 dogs of different breeds, sexes and sizes were evaluated. Animals with clinical signs or ultrasound findings indicative of endocrine disease or thyroid lesions were not included in the study. Using QelaXtoTM 2D software, shear wave velocity data in m/s and color elastograms were evaluated and calculated. A healthy thyroid has a blue color elastogram, indicative of low stiffness, and there was no distinction between adult and elderly dogs, genders or sizes. The reference range for the shear wave velocity of thyroid tissue assessed by 2D shear wave elastography can be between 1.6 and 2.0 m/s with a variation of ±0.889 in adult and elderly dogs.

This work aimed to elucidate how O3 pollution causes loss of regulation of the immune response in both the brain and the intestine. In this work, we studied the effect of exposing rats to low doses of O3 on the association between the antioxidant response of superoxide dismutase (SOD) levels and nuclear factor kappa light chains of activated B cells (NFκB) as a marker of inflammation. Method: 72 Wistar rats were used, divided into six groups that received the following treatments: Control, 7, 15, 30, 60, and 90 days at O3, respectively. After treatment, tissues were extracted and processed using Western blotting, biochemical, and immunohistochemical techniques. The results indicated an increase in 4-hydroxynonenal (4HNE) and Cu/Zn-SOD, a decrease in Mn-SOD, and SOD activity in the substantia nigra, jejunum, and colon decrease. Furthermore, the translocation of NFκB to the nucleus increased in the different organs studied. In conclusion, repeated exposure to ozone alters the regulation of the antioxidant and inflammatory response in the substantia nigra and the intestine. This suggests that these responses are critical in the loss of regulation of the inflammatory response, and they respond to ozone pollution, which could be occurring in the progression of chronic degenerative diseases.

Workplace bullying is common among nurses affecting negatively several work-related variables, such as job burnout and job satisfaction. However, no study until now has examined the impact of workplace bullying on quiet quitting among nurses. Thus, our aim was to examine the direct effect of workplace bullying on quiet quitting and to investigate the mediating effect of coping strategies on the relationship between workplace bullying and quiet quitting in nurses. We conducted a cross-sectional study with a convenience sample of 650 nurses in Greece. We collected our data during February 2024. We used the Negative Acts Questionnaire-Revised, the Quiet Quitting Scale and the Brief COPE to measure workplace bullying, quiet quitting and coping strategies, respectively. We found that workplace bullying and negative coping strategies were positive predictors of quiet quitting, while positive coping strategies was a negative predictor of quiet quitting. Our mediation analysis showed that positive and negative coping strategies partially mediated the relationship between workplace bullying and quiet quitting. In particular, positive coping strategies caused competitive mediation, while negative coping strategies caused complimentary mediation. Nurses’ managers and policy makers should improve working conditions by reducing workplace bullying and strengthening positive coping strategies among nurses.

Immunosenescence refers to age-related alterations of the immune system function affecting both the humoral and cellular arm of immunity. Understanding immunosenescence and its impact on vaccination of older adults is essential since primary vaccine responses in older individuals can fail to generate complete protection, especially vaccines targeting infections with increased incidence among the elderly, such as the respiratory syncytial virus. Here, we review the clinical trials of both candidate and approved vaccines against respiratory syncytial virus (RSV), which include adults aged ≥50 years, with an emphasis on the evaluation of immunogenicity parameters. Currently, there are 10 vaccine candidates and 2 vaccines approved for the prevention of RSV in the older adult population. The number of registered clinical trials for this age group amounts to 32. Our preliminary evaluation of published results and interim analyses of the RSV vaccine clinical trials indicates efficacy in older adult participants, demonstrating immunity levels that closely resemble those of younger adult participants.

Batch and transport experiments were used to investigate the remediation of a loamy sand soil contaminated with Cr(VI) using zero valent iron nanoparticles (nZVI) stabilized by the carboxy methyl cellulose (CMC-nZVI). The effect of pH, ionic strength (IS), and flow rate on the removal efficiency of Cr(VI) were investigated under equilibrium (uniform transport) and non-equilibrium (Two-site sorption) transport using the Hydrus-1D model. The overall removal efficiency ranged from 70 to over 90% based on the chemical characteristics of the CMC-nZVI suspension and the transport conditions. The concentration and pH of the CMC-nZVI suspension had the most significant effect on the removal efficiency and transport of Cr(VI) in the soil. The average removal efficiency of Cr(VI) was increased from 24.1 to 75.5% when the concentration of CMC-nZVI nanoparticles was increased from 10 to 250 mg L-1, mainly because of the increased total surface area at larger particle concentration. Batch experiments showed that removal efficiency of Cr(VI) was much larger under acidic conditions. The average removal efficiency of Cr(VI) reached 90.1 and 60.5 % at pH 5 and 7, respectively. The Two-site sorption model described quite well (r2 = 0.96-0.98) the transport of Cr(VI) in soil as compared to the uniform transport model (r2 = 0.81-0.98). The average retardation of Cr(VI) was 3.51 and 1.61 at pH 5 and 7, respectively, indicating earlier arrival for the breakthrough curves and shorter time to reach maximum relative concentration at lower pH. The Hydrus-1D model has proven to be an efficient tool for assessing the removal of Cr(VI) pollutants, offering innovative, cost-effective, and environmentally friendly remediation methodologies.

Intergenerational Justice entitles the maximum retention of Earth’s Biodiversity. The United Nations COP 15 committed to the protection of 30% of Earth’s terrestrial environments to provide Biospheric Sustainability. However, proactive amphibian sustainability needs support from amphibian Reproduction Technologies, Biobanking, and Conservation Breeding Programs [RBCs]. These technologies include the reliable practice of stimulation of reproduction and the collection of sperm and oocytes, refrigerated and cryopreserved sperm storage, in vitro fertilization. Emerging technologies promise the perpetuation of species solely from biobanked biomaterials. However, although exemplary national programs for amphibian RBCs are now established in the USA and Australia, these potentials are not fully realised resulting in unacceptable biodiversity loss. To fully realise these potentials an independent and democratic global organisation is proposed to, 1) focus on the bioregions with the highest amphibian biodiversity, 2) maximise regional inclusion in international initiatives, and 3) provide for maximum community engagement and financial resources. We present the first overall multidisciplinary review of amphibian RBCs, including their geopolitical, cultural, and scientific background, along with their development and application to economically, efficiently, and reliably, perpetuate amphibian biodiversity. We provide genetic models, the potential for diploid cell cryopreservation to perpetuate species, along with significant new information on methodologies and techniques, and standardise nomenclature for specificity in publications and media consistency.

Artificial intelligence (AI)-based models hold the potential to transform higher education if adopted properly and ethically. A prime example is ChatGPT with earlier studies indicating its widespread adoption in academia and by university students. The current study aimed to identify the factors influencing the attitude towards ChatGPT and its usage among university students in Arab countries. A previous survey instrument termed Technology Acceptance Model Edited to Assess ChatGPT Adoption (TAME-ChatGPT) was administered online using a convenience-based approach among the contacts of the authors. Confirmatory factor analysis (CFA) for the survey constructs was done using root mean square error of approximation (RMSEA), standardized root mean square residual (SRMR), comparative fit index (CFI), and Tucker-Lewis index (TLI). The final study sample comprised a total of 2240 participant divided as follows: Iraq (n=736, 32.9%), Kuwait (n=582, 26.0%), Egypt (n=417, 18.6%), Lebanon (n=263, 11.7%), and Jordan (n=242, 10.8%). A total of 1048 respondents heard of ChatGPT before the study (46.8%), of which 551 used ChatGPT (52.6%). The mean scores of TAME-ChatGPT constructs showed that the ease of ChatGPT use, positive attitude towards technology and social influence, higher perceived usefulness, the influence of behavioral/cognitive factors, low perceived risks and low anxiety were the determinants of positive attitude to ChatGPT and its use. For both the attitude and usage scales of TAME-ChatGPT, CFA collectively yielded satisfactory fit indices as indicated by low RMSEA and SRMR together with high CFI and TLI. Multivariate analysis showed that attitude to ChatGPT use was significantly influenced by country of residence, age, university type, and the latest grade point average of the students. The current study confirmed the validity of TAME-ChatGPT as a survey instrument to assess the possible determinants of ChatGPT use among university students in Arab countries. The study findings highlighted that successful adoption of ChatGPT in higher education could be dependent on perceived ease of use, usefulness, positive attitudes to technology, social influence, behavioral/cognitive factors, lower anxiety, and minimal perceived risks. The utility of ChatGPT in higher education requires policies that should be tailored for various settings, considering the differences observed in attitude towards ChatGPT among participating students in this study.

Endoscopic submucosal dissection (ESD) is almost always performed with a sedative because of the longer procedure times involved. The risk of post-ESD deep vein thrombosis (DVT) has been reported as relatively high, and D-dimer levels are sometimes elevated after ESD. This retrospective study evaluated factors affecting changes in D-dimer levels from before to after ESD to identify causes of elevated D-dimer levels after ESD. This retrospective analysis included 117 patients with gastrointestinal tumors resected using ESD. After excluding 8 patients with pre-ESD levels of D-dimer >1.5 μg/mL, factors correlating with changes in D-dimer from before to after ESD were analyzed using logistic regression analysis in 109 patients. Sedation was accomplished primarily using midazolam, but because the sedative effect of midazolam shows marked inter-individual variability, a “corrected midazolam dose” was determined by dividing the total midazolam dose by the initial dose to correct for inter-individual differences in the sedative effect of midazolam. This value was used as one potential explanatory variable in subgroup analysis of the 103 patients who received midazolam. In subgroup analysis using the corrected midazolam dose as an explanatory variable, only corrected midazolam dose correlated with a change in D-dimer ≥ 1.0 μg/mL in multivariate analysis (odds ratio [OR]=1.5, 95% confidence interval [CI] 0.43–0.95; P=0.030). Corrected midazolam dose correlated with increases in post-ESD D-dimer levels. This potential relationship indicates that patients undergoing ESD and requiring extended sedation may be at increased risk of DVT.

Epizootic haemorrhagic disease (EHD) is a Culicoides-borne viral disease caused by epizootic haemorrhagic disease virus (EHDV) and associated with clinical manifestations in cervids and bovids. In late September 2021, EHDV was reported in cattle farms in central/western Tunisia. It rapidly spread throughout the country with more than 200 confirmed outbreaks. A combination of classical and molecular techniques was applied to characterize the causative virus as a member of EHDV-8 serotype. This is the first evidence of EHDV- 8 circulation since 1982 when the prototype EHDV-8 strain was isolated in Australia. This work highlights the urgent need for vaccines for a range of EHDV serotypes.

Monkeypox is a rare disease which is rising nowadays in different countries since the first case in the UK was diagnosed on May 6, 2022, by the United Kingdom (UK) Health Security Agency. Then more than 12,500 cases were identified in over 68 countries up to July 18, 2022. In endemic areas, the monkeypox virus (MPXV) is commonly transmitted through zoonosis, while in non-endemic regions, it is spread through human-to-human transmission. Symptoms can include flu-like symptoms, rash, or sores in hands, feet, genitalia, or anus. In addition, people who did not take the smallpox vaccine were more liable to be affected than others. The exact pathogenesis and mechanisms are still unclear; however, most identified cases are reported in men who have sex with other men (MSM). According to the CDC, transmission can happen with any sexual or non-sexual contact with the infected person. However, a recent pooled meta-analysis reported that sexual contact is involved in more than 91% of the cases. Also, it is the first time that semen analysis for many patients has shown positive monkeypox virus DNA. Therefore, in this review, we will describe transmission methods for MPXV while focusing mainly on potential sexual transmission and associated sexually transmitted infections. We will also highlight the preventive measures that can limit the spread of the diseases in this regard.

We report four allelic variants (3 novel) in three genes previously established as causal for hypopituitarism or related disorders. A novel homozygous variant in the growth hormone gene, GH1 c.171delT (p. Phe 57Leufs * 43), was found in a male patient with severe isolated growth hormone deficiency (IGHD) born to consanguineous parents. A SOX3 allelic variant (p.Met304Ile) was found in a male patient with IGHD and hypoplastic anterior pituitary. YASARA, a tool to evaluate protein stability, suggests that p.Met304Ile destabilizes the SOX3 protein (ΔΔG = 2.49 kcal/mol). A rare, heterozygous missense variant in the TALE homeobox protein gene, TGIF1 (c.268C>T:p.Arg90Cys) was found in a patient with combined pituitary hormone deficiency (CPHD), diabetes insipidus, and syndromic features of holoprosencephaly (HPE). A novel heterozygous TGIF1 variant (c.82T>C:p.Ser28Pro) was identified in a patient with CPHD, pituitary aplasia and ectopic posterior lobe. Both TGIF1 variants have an autosomal dominant pattern of inheritance with incomplete penetrance. In conclusion, we have found allelic variants in 3 genes in hypopituitarism patients. We discuss these variants and associated patient phenotypes in relation to previously reported variants in these genes, expanding our knowledge of the phenotypic spectrum in patient populations.

Plans are currently being drafted for the next decade of action on biodiversity – both the post-2020 Global Biodiversity Framework of the Convention on Biological Diversity (CBD) and Biodiversity Strategy of the European Union (EU). Freshwater biodiversity is disproportionately threatened and under-prioritized relative to the marine and terrestrial biota, despite supporting a richness of species and ecosystems with their own intrinsic value and providing multiple essential ecosystem services. Future policies and strategies must have a greater focus on the unique ecology of freshwater life and its multiple threats, and now is a critical time to reflect on how this may be achieved. We identify priority topics including environmental flows, water quality, invasive species, integrated water resources management, strategic conservation planning, and emerging technologies for freshwater ecosystem monitoring. We synthesize these topics with decades of first-hand experience and recent literature into 14 special recommendations for global freshwater biodiversity conservation based on the successes and setbacks of European policy, management and research. Applying and following these recommendations will inform and enhance the ability of global and European post-2020 biodiversity agreements to halt and reverse the rapid global decline of freshwater biodiversity.

The aim of this study was to examine the oxidation of human serum albumin (HSA) caused by oxidative stress after an exhaustive exercise such as ultra-marathon race. Thus, blood samples from 12 adult runners who underwent a 103 km mountain ultra-marathon race were collected pre- and 24, 48 and 72 h post race. HSA was partially purified using affinity chromatography and then was subjected to Western blot analysis for disulfide dimers determination, indicating oxidation. The results were correlated with those from a previous study in which the same samples were analyzed using different oxidative stress markers and a good correlation with protein carbonyls (PC) at all time points was observed. Moreover there was a significant correlation with static oxidation-reduction potential (sORP) at 24 h, and a negative correlation with capacity oxidation-reduction potential (cORP) at 24 and 48 h. In addition, an individual analysis of albumin dimers exhibited great inter-individual differences. This inter-individual variability in the oxidation of HSA may suggest different interventions (e.g. through diet) in order to confront the effects on athletes’ organism after a strenuous exercise. In conclusion, this study supported the importance of the assessment of albumin dimers as a predictive marker for exercise-induced oxidative stress.

The dispersal potential of crown-of-thorns starfish (CoTS) larvae is important in understanding both the initiation and spread of population outbreaks, and is fundamentally dependent upon how long larvae can persist while still retaining the capacity to settle. This study quantified variation in larval survivorship and settlement rates for CoTS maintained at three different chlorophyll concentrations (0.1, 1.0 or 10.0 µg.L^-1), achieved by varying densities of single-celled flagellate phytoplankton, Proteomonas sulcata. Based on the larval starvation hypothesis we expected that low to moderate algal concentrations would significantly constrain both survival and settlement. CoTS larvae were successfully maintained for up to 50 days post-fertilization, but larval survival differed significantly between treatments. Survival was greatest at intermediate (1.0 µg.L^-1) chlorophyll concentrations, and lowest at highest (10.0 µg.L^-1) chlorophyll concentrations. Rates of settlement were also highest at intermediate (1.0 µg.L^-1) chlorophyll concentrations and peaked at 22 days post-fertilization. Peak settlement was delayed at low chlorophyll concentrations, probably reflective of delayed development, but there was no evidence of accelerated development at high chlorophyll concentrations. CoTS larvae were capable of settling 17-43 days post-fertilization, but under optimum conditions with intermediate chlorophyll concentrations, peak settlement occurred at 22 days post-fertilization. Moderate increases in nutrient concentrations and algal densities may increase the number of CoTS that effectively settle, but are unlikely to influence dispersal dynamics.

The microbial contamination in food packaging have been a major concern that paved the way for the search for natural based new anti-microbial agents, such as modified α-mangostin. In the present work, twelve synthetic analogs were obtained via semi-synthetic modification of α-mangostin by Ritter reaction, reduction by palladium-carbon (Pd-C), alkylation, and acetylation. The evaluation of the anti-microbial potential of the synthetic analogs showed higher therapeutic value than the parent molecule. The anti-microbial studies proved that I E showed higher antibacterial activity whereas I I showed most significant antifungal activity. Due to their microbial properties, modified α-mangostin can be utilized as active anti-microbial agents in food packaging.

Background: Leishmaniasis is a significant global public health issue that is caused by parasites from Leishmania genus. With limited treatment options and rising drug resistance, there is a pressing need for new therapeutic approaches. Molecular chaperones, particularly Hsp90, play a crucial role in parasite biology and are emerging as promising targets for drug development. Objective: This study evaluates the efficacy of 17-DMAG in treating BALB/c mice from cutane-ous leishmaniasis through in vitro and in vivo approaches. Materials and Methods: We assessed 17-DMAG cytotoxic effect on bone marrow-derived mac-rophages (BMMΦ) and its effects against L. braziliensis promastigotes and intracellular amastigotes. Additionally, we tested the compound's efficacy in BALB/c mice infected with L. braziliensis via intraperitoneal administration to evaluate the reduction of lesion size and de-crease of parasite load in the ears and lymph nodes of infected animals. Results: 17-DMAG showed selective toxicity [selective index=432) towards Leishmania amastigotes, causing minimal damage to host cells. The treatment significantly reduced lesion sizes in mice and results in parasite clearance from ears and lymph nodes. It also diminished in-flammatory responses and reduced the release of pro-inflammatory cytokines (IL-6, IFN-g, TNF) and the regulatory cytokine, IL-10, underscoring its dual leishmanicidal and anti-inflammatory properties. Conclusion: Our findings confirm the potential of 17-DMAG as a viable treatment for cutaneous leishmaniasis and support further research into its mechanisms and potential applications against other infectious diseases.

PET imaging of bacterial infection could potentially provide added benefit for patient care by non-invasive means. [68Ga]Ga-desferrioxamine B – a radiolabelled siderophore – shows specific uptake by human-pathogenic bacteria like Staphylococcus aureus or Pseudomonas aeruginosa as well as sufficient serum stability for clinical application. Here, we provide data for automated production of [68Ga]Ga-desferrioxamine B on two different cassette based synthesis modules (Modular-Lab PharmTracer and GRP 3V) using commercially available cassettes together with an approved 68Ge/68Ga radionuclide generator. Quality control including determination of radiochemical purity as well as a system suitability test was set up via RP-HPLC on a C18 column. The two described production processes, using an acetic acid/acetate buffer system with ascorbic acid as a radiation scavenger for radiolabelling, yield ready-to-use formulations with sufficient activity yield. Batch data showed radiochemical purity of &gt;95 % as determined by RP-HPLC and ITLC as well as excellent stability over 2 hours post production. Specifications for routine production were set up and validated with four master batches for each synthesis module. Based on this study, an academic clinical trial for imaging of bacterial infection was initiated. Both described synthesis methods enable reproducible, automated in-house production of [68Ga]Ga-desferrioxamine B for clinical application.

The aim of this study was to analyze the relationship between healthy vascular aging (HVA) and the Mediterranean diet alongside other lifestyles in a Spanish population aged 35 to 75 years without previous cardiovascular diseases. Methods: Cross-sectional descriptive study with 501 individuals aged 35 to 75 years recruited from five health centers by random sampling stratified by age and sex (55.90±14.24 years, 49.70% men). HVA was determined in two steps. Step 1: Subjects with vascular damage to the carotid arteries or peripheral arterial disease were classified as non-HVA. Step 2: The study population was classified by age and sex using the percentiles of the vascular aging index (VAI), with VAI ≤p25 considered HVA and >p25 considered non-HVA. The VAI was estimated using the following formula (VAI = (log (1.09) × 10 cIMT + log (1.14) cfPWV) × 39.1 + 4.76. Carotid-femoral pulse wave velocity (cfPWV) was measured with the SphygmoCor® device and carotid intima-media thickness using Sonosite Micromax® ultrasound. Mediterranean diet (MD) adherence, alcohol and tobacco use were recorded through validated questionnaires. Physical activity was assessed with the ActiGraph-GT3X® accelerometer. Results: The mean VAI value was 61.23±12.86; (Men 63.47±13.75 and women 59.04±11.54; p

Software-Defined Networking (SDN) has revolutionized network management by providing unprecedented flexibility, control, and efficiency. However, its centralized architecture introduces critical security vulnerabilities. This paper presents an innovative approach to securing SDN environments using IOTA 2.0 smart contracts. The proposed system leverages the IOTA Tangle, a directed acyclic graph (DAG) structure, to enhance scalability and efficiency while eliminating transaction fees and reducing energy consumption. We introduce three smart contracts—Authority, Access Control, and DoS Detector—to ensure secure network operations, prevent unauthorized access, and mitigate denial-of-service attacks. Through comprehensive simulations using Mininet and the ShimmerEVM IOTA Test Network, we demonstrate the efficacy of our approach in enhancing SDN security. Our findings highlight the potential of IOTA 2.0 smart contracts to provide a robust, decentralized solution for securing SDN environments, paving the way for further integration of blockchain technologies in network management.

Staphylococcus aureus is an opportunistic human pathogen and a leading cause of bloodstream infections. It can acquire different antibiotic resistance genes, leading to treatment failure. Aim: We elaborate on the genomic characteristics; antibiotic resistance, virulence, pathogenicity, phylogenomics and clonal diversity of S. aureus implicated in bloodstream infections. Six multidrug-resistant (MDR) S. aureus, three methicillin-resistant S. aureus (MRSA) and three methicillin-sensitive S. aureus obtained from blood cultures underwent whole genome sequencing and bioinformatics analysis. All isolates carried different permutations and combinations of resistance genes including, blaZ, mecA, aac(6')-aph (2''), ant(9)-Ia, ant(6)-Ia, mepR, fosB, norA, norC, lmrS, arlS, arlR, mgrA, kdpD and sdrM. We found 6 spa types (t9475, t355, t045, t1265, t1257, and t7888) with varying profiles of virulence genes responsible for immune invasion, enterotoxins, adhesion/biofilm, haemolysins, and leukotoxins. Panton-Valentine leukocidin (Luk-PV) was found in one MSSA isolate. Two SCCmec types IVd(2B) and I(1B) were identified. Isolates belonged to four multilocus sequence types (MLSTs), the most common of which was ST5 (n=3). The STs were clustered into two clonal complexes CC5 and CC8. We found two MRSA clones typed as ST5-CC5-t045-SCCmec_I(1B), and the human-associated MRSA endemic clone ST612-CC8-t1257-SCCmec_IVd(2B). The insertion sequences IS30 and IS6 associated with virulence were found in two isolates. The presence of virulent MDR S. aureus in bloodstream infections poses a clinical concern because of limited treatment options and increased risk of mortality.

Background: Subclinical myocardial injury (SCMI) is associated with an increased risk of poor cardiovascular disease (CVD) outcomes. Understanding the underlying risk factors for SCMI is crucial for the prevention and management of CVD. We hypothesized that atherogenic dyslipidemia, a combination of high triglycerides (TG) and low high-density lipoprotein cholesterol (HDL-C), is associated with an increased risk of SCMI. Methods: This analysis from the third National Health and Nutrition Examination Survey (NHANES-III) included 7,093 participants (age 59.3±13.4 years, 52.8% women, and 49.4% White) free of CVD. Atherogenic dyslipidemia was defined as TG ≥150 mg/dL and HDL-C <40 mg/dL in men or <50 mg/dL in women. A validated electrocardiographic-based cardiac infarction injury score (CIIS) ≥10 was considered positive for SCMI. Multivariable logistic regression analysis was used to examine the association of different combinations of TG and HDL-C groups, including atherogenic dyslipidemia with SCMI. Results: About 22.5% (n=1,594) of participants had atherogenic dyslipidemia, and 26.3% (n=1862) had SCMI. Compared to participants with normal TG and normal HDL-C, those with atherogenic dyslipidemia had a higher prevalence of SCMI (31.2% vs. 23.9%, p-value <0.001). In a multivariable logistic regression model, atherogenic dyslipidemia was associated with the highest odds of SCMI followed by high TG/normal HDL-C, then low HDL-C/normal TG [OR (95% CI): 131 (1.14,1.52), 1.13 (0.97,1.33), and 1.01(0.86,1.20), respectively). Conclusions: Atherogenic dyslipidemia is associated with a higher risk of SCMI, which highlights the role of nontraditional risk factors in the development of subclinical CVD.

This article examines experiments with elastic material, specifically the deformation of an elastic tube under hydrostatic pressure with a constant flow of fluid inside. This flow induces a pulsatile movement within the elastic tube. Preliminary results are compared with a theoretical model that combines longitudinal and transverse waves. During the experiment, images at various stages of deformation were captured and analyzed. The objective is to better understand the behavior of elastic materials under these conditions and validate the proposed theoretical model through detailed experimental observations, providing a deeper insight into the dynamics of deformation in deformable materials.

This study investigates the influence of pyrolysis temperature on the main properties of BSG (brewer's spent grain) biochar and evaluates its suitability as an energy vector and as a substrate component. Pyrolysis tests were carried out at 673, 773, and 873 K. Bioenergy indexes were calculated for BSG and its biochar, and germination tests were carried out to obtain lentil sprouts. The results showed that the BSG biochar obtained at the lowest temperature biochar presented the best performance for use as biofuel. Regarding the germination tests, the different biochars were applied at 4 doses, and the evaluated parameters such as germination percentage, germination rate, mean germination time, and seed vigor were strongly influenced by the biochar addition. The biochar at 773 K added at a dose of 5% doubled the values of mean germination time, seed vigor, and time for 50% of the seeds to emerge compared to the control, constituted only with distilled water. The sustainable BSG valorization through pyrolysis reduces waste and contributes to circular economy practices by transforming industrial by-products into valuable resources for energy and agriculture. This approach highlights the importance of sustainability in reducing the environmental impact of industrial waste and promoting renewable energy sources.

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.

The detection, characterization, and monitoring of SARS-CoV-2 recombinant variants is a challenge to public health authorities worldwide. Recombinant variants, composed of two or more SARS-CoV-2 lineages, often have unknown impacts on transmission, immune escape, and virulence in the early stages of emergence. We examined 4,213 SARS-CoV-2 recombinant SARS-CoV-2 genomes collected between 2020 and 2022 from California to describe regional and statewide trends in prevalence. Many of these recombinant genomes, such as those belonging to the XZ lineage, or novel recombinant lineages, likely originated within the state of California. We discuss the challenges and limitations surrounding Pango lineage assignments, the use of publicly available sequence data, and adequate sample sizes for epidemiologic analyses. Although these challenges will continue as SARS-CoV-2 sequencing volumes decrease globally, this study enhances our understanding of SARS-CoV-2 recombinant genomes to date while providing a foundation for future insights into emerging recombinant lineages.

Exercise has increasingly been recognized as an adjunctive therapy for alcohol-use disorder (AUD), yet our understanding of its underlying neurological mechanisms remains limited. This knowledge gap impedes the development of evidence-based exercise guidelines for AUD treatment. Chronic ethanol (EtOH) exposure has been shown to upregulate and sensitize kappa opioid receptors (KORs) in the nucleus accumbens (NAc), which is innervated by dopamine (DA) neurons in the midbrain ventral tegmental area (VTA), which may contribute to AUD-related behaviors. In this study, we investigated the impact of voluntary exercise in EtOH-dependent mice on EtOH consumption, KOR and DOR expression in the NAc and VTA, and functional effects on EtOH-induced alterations in DA release in the NAc. Our findings reveal that voluntary exercise reduces EtOH consumption, reduces KOR and enhances DOR expression in the NAc, and modifies EtOH-induced adaptations in DA release, suggesting a competitive interaction between exercise-induced and EtOH-induced alterations in KOR expression. We also found changes to DOR expression in the NAc and VTA with voluntary exercise but no significant changes to DA release. These findings elucidate the complex interplay of AUD-related neurobiological processes, highlighting the potential for exercise as a therapeutic intervention for AUD.

Gestational diabetes mellitus (GDM) triggers alterations in the maternal gut microbiome. Alongside metabolic shifts, microbial products may impact clinical factors and influence pregnancy outcomes. Here, we performed two separate analyses to integrate the maternal microbiome-metabolomic differences from a subset of the “Choosing Healthy Options in Carbohydrate Energy” (CHOICE) study. Women diagnosed with GDM were randomized to a diet higher in complex carbohydrates (CHOICE, n=18, 60% complex carbohydrate/25% fat/15% protein) or a conventional GDM diet (CONV, n=16, 40% carbohydrate/45% fat/15% protein). All meals were provided, diets were eucaloric, and fiber content was similar. CHOICE diet was associated with increases in TMAO, lysophosphotidylcholines, indoxyl sulfate, and several triglyceride (TG) species, while CONV diet was associated with higher plasma hippuric acid, aspartic acid, betaine, glutamic acid, indole propionic acid, and indoleacetic acid, suggesting that differences in lipid metabolism and tryptophan utilization pathways are linked to specific maternal diets. We also identified two latent metabolic groups not associated with either diet treatment: one metabolome associated with higher fasting glucose, and the other associated with higher fasting TGs after 7 weeks on either diet. Our study underscores the importance of utilizing dietary approaches to optimize maternal-fetal health outcomes in GDM treatment.

The article aims to present the results of research on anaerobic digestion (AD) of waste wafers (WF - control) and co-substrate system - waste wafers and cheese (WFC - control), combined with digested sewage sludge. The aim of the study was to evaluate the physicochemical parameters of the chitosan/perlite (Ch/P; 3:1) carrier material and to verify its effect on the directions of change of the bacterial microbiome, removal kinetics of organic matter and AD process efficiency. The experiment was conducted in a laboratory, in a periodical mode of operation of bioreactors, under mesophilic conditions. The results of analyses of morphological-dispersive, spectroscopic, adsorption, thermal and microbiological properties confirmed that the tested carrier material can be an excellent option to implement in biotechnological processes, especially in anaerobic digestion. The microstructural properties of the carrier were influenced by both components: perlite determined the development of the specific surface area, while chitosan shaped the porosity of the system. The thermal properties were determined by the less heat-resistant component, present in a threefold higher weight proportion, i.e. chitosan. The evaluation of quantitative and qualitative changes in the genetic diversity of bacterial communities, carried out using Next Generation Sequencing (NGS), showed that the material has a modifying effect on the bacterial microbiome. Amount of bacteria from phyla Actinobacteria, Bacteroidetes, Campilobacterota, Chloroflexi, Euryarchaeota, Planctomycetes, and Proteobacteria decreased while Firmicutes, Synergistetes, and Thermotogae increased during the course of the experiment. The shapes of the FT-IR spectra indicated a dependence of the degradation rate on both the presence of the carrier and the cosubstrate system. Monitoring of the course of AD was carried out by measuring key parameters for the stability of the process: pH, VFA and VFA/TA ratio (volatile fatty acids/total alkalinity). As a result, an increase in the volume of biogas/methane produced, under the influence of the carrier, was recorded for WF-control by 12.05% and for WFC-control by 19.16%. The volume of methane for the WF-control increased from 351.72 m3 Mg-1 VS to 411.14 m3 Mg-1 VS, while for the cosubstrate sample it increased from 476.84 m3 Mg-1 VS to 518.08 m3 Mg-1 VS, confirming the validity of combining the respective cosubstrate with microbial carrier in anaerobic bioreactor.

A pathway frequently altered in cancer is glutaminolysis where glutaminase (GA) catalyses the main step: the deamidation of glutamine to form glutamate and ammonium. There are two types of GA isozymes, named GLS and GLS2, which differ considerably in their expression patterns and can even perform opposing roles in cancer. GLS correlates with tumor growth and proliferation, while GLS2 may function as a context-dependent tumor suppressor. However, both isoenzymes have been described as essential molecules handling oxidant stress because of their involvement in glutathione production. We have reviewed the literature to highlight the critical roles of GLS and GLS2 to restrain ROS and regulate both cellular signaling and metabolic stress due to their function as indirect antioxidant enzymes and also by modulating both reductive carboxylation and ferroptosis. Blocking GA activity appears to be a potential strategy to dual activate ferroptosis and inhibit cancer cell growth in a ROS-mediated mechanism.