Babesia species infect a very wide range of mammal hosts across the globe and zoonotic infections are of growing concern. Several species of the Babesia genus infect dogs and some of these cause significant morbidity and mortality. The Apicomplexan parasite resides within the red cell and infections result in direct damage to the host through intra- and extravascular hemolysis. An exuberant inflammatory response by the host to some species of Babesia parasites also result in significant collateral damage to the host. Canine infections have been the subject of much study as the wellbeing of these companion animals is increasingly threatened by the spread of tick vectors and an increasingly mobile dog population. There are no widely available and effective vaccines and effective treatment can be challenging. Understanding disease pathogenesis underlies the development of new treatments. The varying pathogenicity of the various Babesia parasite species that infect dogs offers an opportunity to explore the molecular basis for the wide range of disease caused by infection with this parasite genus. In this review we focus on what has been reported about the clinical presentation of Babesia infected dogs in an attempt to compare the severity of disease caused by different Babesia species.

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

The physiological response to a psychological stressor broadly impacts energy metabolism. In-versely, changes in energy availability affect the physiological response to the stressor in terms of hypothalamus, pituitary adrenal axis (HPA) and sympathetic nervous system activation. Glu-cocorticoids, the endpoint of the HPA axis, are critical checkpoints in endocrine control of ener-gy homeostasis and have been linked to metabolic diseases including obesity, insulin resistance and type 2 diabetes. Glucocorticoids, through the glucocorticoid receptor, activate transcription of genes associated with glucose and lipid regulatory pathways and thereby control both physi-ological and pathophysiological systemic energy homeostasis. Here, we summarize the current knowledge of glucocorticoid functions in energy metabolism and systemic metabolic dysfunc-tion, particularly focusing on glucose and lipid metabolism. There are elements in the external environment that induce lifelong changes in the HPA axis stress response and glucocorticoid levels, the most prominent are early-life adversity, or exposure to traumatic stress. We hypothe-sise that when the HPA axis is so disturbed after early-life adversity, it will fundamentally alter hepatic gluconeogenesis, inducing hyperglycaemia, and hence crystalise the significant lifelong risk of developing either the metabolic syndrome, or type 2 diabetes. This gives a “Jekyll and Hyde” role to gluconeogenesis, providing the necessary energy in situations of acute stress, but driving towards pathophysiological consequences when the HPA axis has been altered.

There are many ‘faces’ of early life adversity (ELA), such as childhood trauma, institutionalization, abuse or exposure to environmental toxins. These have been implicated in the onset and severity of a wide range of chronic non-communicable diseases later in life. The later-life disease risk has a well-established immunological component. This raises the question as to whether accelerated immune-ageing mechanistically links early-life adversity to the lifelong health trajectory resulting in either ‘poor’ or ‘healthy’ ageing. Here we examine observational and mechanistic studies of ELA and inflammageing, highlighting common and distinct features in these two life stages. Many biological processes appear in common including reduction in telomere length, increased immuno-senescence, metabolic distortions and chronic (viral) infections. We propose that ELA shapes the developing immune, endocrine and nervous system in a non-reversible way, creating a distinct phenotype with accelerated immuno-senescence and systemic inflammation. We believe that ELA acts as an accelerator for inflammageing and age-related diseases. Furthermore, we now have the tools and cohorts to be able to dissect the interaction between early life adversity and later life phenotype. This should, in the near future, allow us to identify the ecological and mechanistic processes that are involved in ‘healthy’ or accelerated immune-ageing.

Antibiotic resistance is a pressing global and planetary health challenge. Links between climate change, antibiotic use and the emergence of antibiotic resistance have been well documented, but less attention has been given to the impact(s) of earth systems on specific bacterial livestock diseases at a more granular level. Understanding the precise impacts of climate change on livestock health – and in turn the use of antibiotics to address that ill-health – is important in providing an evidence base to tackle such impacts and to develop practical, implementable and locally acceptable solutions within and beyond current antibiotic stewardship programmes. In this paper, we set out the case for better integration of earth scientists and their specific disciplinary skill set (specifically, problem-solving with incomplete/fragmentary data; the ability to work across four dimensions and at the interface between the present and deep/geological time) into planetary health research. We then discuss a methodology that makes use of risk mapping, a common methodology in earth science but less frequently used in health science, to map disease risk against changing climatic conditions at a granular level. This will enable predictions of future disease risk and risk impacts based on predicted future climate conditions, and thus provide an evidence base for planetary health activists to influence policy and develop mitigations. Our case study – of climate conditions’ impact on livestock health in Karnataka, India – clearly evidences the benefit of integrating earth scientists into planetary health research.

The microalgae Phaeodactylum tricornutum (PT) is distinguished by its rich nutrient profile, characterized by well-documented neuroprotective activities, including fucoxanthin (FX), a major carotenoid, and polyunsaturated omega-3 fatty acids (n-3 PUFA). The current study aims to evaluate the protective effects of a standardized extract of PT (Mi136) containing 2% FX on cognitive function, oxidative stress, and inflammation parameters in a mouse model of accelerated aging. Seventy-two (72) male mice were randomly assigned to the blank control group (BC), negative control group (NC), and four similar microalgae extract of PT groups (branded as BrainPhytTM) with different human equivalent doses. From day 01 to day 51, mice in the BC group were injected with a 0.9% normal saline solution, while mice in all other groups were subcutaneously injected with D-galactose (D-Gal) at a dose of 150 mg/kg once per day, five days per week. Results indicated that, for the three higher microalgae extract of PT dose groups, spatial cognitive function, swim latency, and step-through latency impairments induced by chronic D-Gal intoxication were significantly and fully inhibited, with mean values similar to those in the BC group during each day of testing. Similar benefits were observed in biochemical analysis, specifically regarding brain and plasma levels of lipid peroxidation, TNF-α, and IL-6 markers. These data underscore the positive effects of a standardized extract of PT containing 2% FX on cognitive function parameters such as spatial working memory, long-term memory, and short-term memory through the regulation of oxidative stress and inflammation pathways.

Uranium (U) is enriched in the waters of the southern Colorado Plateau, including waters of the Navajo Nation. The region has naturally occurring U in rocks and a history of U mining which may increase U concentrations in waters. Despite prior research into the concentration of U in the waters of the Navajo Nation, a framework has not been established to understand the variation of U in the region’s groundwater. To this end, we examined data from five studies to establish where and why U is likely to be enriched in waters of the southern Colorado Plateau. We show that U concentrations are related to the presence of U-rich rock bodies, surface elevation, and local aquifer salinity. Additionally, we show that the distance to the nearest mine is a significant predictor of U in water sources. Our work can act as a guide for local water withdrawal, regional water remediation and mitigation efforts, and provides a means for understanding the geographical patterns of U concentration in waters of the southern Colorado Plateau.

Our study assessed the impact of using ovitraps with pyriproxyfen on mosquito populations and the feasibility of using human saliva samples to test for seroconversion to dengue virus (DENV). We used a quasi-experimental research design by forming the intervention (n=220) and the control (n=223) groups in neighboring Taguig City, Philippines, over four months. Socio-demographic data, entomological indices, and IgG antibodies against DENV were measured. Associations between the implementation of ovitraps dosed with pyriproxyfen and mosquito densities (percentage positive ovitraps and container indices) and DENV seroconversion were calculated post-intervention in Months 2, 3, and 4. Among participants recruited at baseline, 17 and 13 were seropositive for dengue (DENV) in the intervention and control groups, respectively. Both entomological indices were lower in the treated area than the control site at months two, three, and four post-interventions but not earlier. Dengue seroconversions rates did decrease in the treated population but not significantly so. In conclusion, the use of PPF-treated ovitraps impacted the mosquito population but not the seroconversion rates. Compliance to provide saliva samples and the ability to detect IgG antibodies within these samples were encouraging and suggested that further studies on a larger population and longer duration are warranted.

Uganda is one of the poorest nations in the world. To address the developmental challenges and understand social and economic status, it is important to obtain accurate data in a timely manner. Many studies have demonstrated that nighttime lights (NTL) can be used to measure human activities. Nevertheless, methods developed from these studies (1) suffer from coarse resolutions, (2) fail to capture the nonlinearity and multi-scale variability of geospatial data, and (3) perform poorly for agriculture-dependent regions. This study proposes a new enhanced light intensity model (ELIM) to estimate the Gross Domestic Product (GDP) at sub-national scales for Uganda. This model is developed by combining the NTL data from the Suomi National Polar-orbiting Partnership Visible Infrared Imaging Radiometer Suite (NPP-VIIRS), the population data from the Global Human Settlement Layer (GHSL), and information on agricultural production and market prices across several commodity types. This resulted in a gridded dataset for GDP and GDP per capita for Uganda at 1 km spatial resolution and district level to capture the spatial heterogeneity in economic activity.

To stabilize the Earth’s climate a large-scale transition is needed to non-carbon emitting renewable energy technologies like wind and solar energy. Although these renewable energy sources are now lower-cost than fossil fuels, their inherent intermittency make them unable to supply a constant load without storage. To address these challenges rechargeable electric batteries are currently the most promising option; however, their high capital costs limit current deployment velocities. To both reduce the cost as well as improve performance 3D printing technology has emerged as a promising solution. This literature review provides the state-of-the-art enhancements of battery properties with 3D printing including efficiency, mechanical stability, energy and power density, customizability and sizing, production process efficiency, material conservation and environmental sustainability as well as the progress in solid-state batteries. The principles, advantages, limitations, and recent advancements associated with the most common types of 3D printing are reviewed focusing on their contributions to the battery field. 3D printing batteries offer design flexibility, material flexibility, reduces pack weight, minimizes material waste, increases the range of applications and has the potential to reduce costs. As 3D printing technologies become more accessible, the prospect of cost-effective production for customized batteries is extremely promising.

Consumption of prebiotic fibers to modulate the human gut microbiome is a promising strategy to positively impact health. Nevertheless, given the compositional complexity of the microbiome and its inter-individual variances, generalized recommendations on the source or amount of fiber supplements remain vague. This problem is further compounded by availability of tractable in vitro and in vivo models to validate certain fibers. We employed a gnotobiotic mouse model containing an a priori characterized 14-member synthetic human gut microbiome (SM) for their ability to metabolize a suit of fibers in vitro; the SM contains 14 different strains belonging to five distinct phyla. Since soluble purified fibers have been a common subject of studies, we specifically investigated the effects of concentrated raw fibers (CRFs)—containing fibers from pea, oat, psyllium, wheat and apple—on the compositional and functional alterations in the SM. We demonstrate that, compared to a fiber-free diet, CRF supplementation increased the abundance of fiber-degraders namely Eubacterium rectale, Roseburia intestinalis and Bacteroides ovatus and decreased the abundance of the mucin-degrader Akkermansia muciniphila. These results were corroborated by a general increase of bacterial fiber-degrading α-glucosidase enzyme activity. Overall, our results highlight the ability of CRFs to enhance the microbial fiber-degrading capacity.

Early Life Adversity (ELA) is closely associated with the risk for developing diseases later in life, such as autoimmune diseases, type-2 diabetes and cardiovascular diseases. In humans, early parental separation, physical and sexual abuse or low social-economic status during childhood are known to have great impact on brain development, in the hormonal system and immune responses. Maternal deprivation (MD), the closest animal model available to the human situation, is known to similarly induce long lasting behavioural effects, to cause changes in the HPA axis and to have an impact in the immune system. Even though the immune responses to potential pathogens after early stress have been somehow documented, the mechanisms by which they occur are still not fully understood. Here, we have demonstrated that maternal separation, in both humans and rats, significantly affects the sensitivity of the immune system in adulthood. Particularly, NK cells’ profile and response to target cell lines are significantly changed after childhood adversity. These immune cells in rats are not only less cytotoxic towards YAC-1 cells, but also show a clear increase in the expression of maturation markers after 3h of maternal separation. Similarly, individuals who suffered from ELA display significant changes in the cytotoxic profile of NK cells together with decreased degranulation capacity. Altogether, these results lead us to conclude that one of the key mechanisms by which the immune system becomes impaired after ELA might be due to a shift on the senescent state of the cells, specifically NK cells. Elucidation of such a mechanism highlights the importance of ELA prevention and how NK targeted immunotherapy might help attenuating ELA consequences.

There is a need for versatile in vivo nuclear imaging reporter systems to foster preclinical and clinical research. We explore the applicability of the SNAPTag and novel radiolabeled small-molecule ligands as a versatile reporter gene system for in vivo nuclear imaging. SNAPTag is a high-affinity protein tag used in a variety of biochemical research areas and based on the suicide DNA repair enzyme O6-methylguanine methyl transferase (MGMT). Its ligands are well suited for reporter gene imaging as the benzyl guanine core scaffold can be derivatized with fluorescent or radiolabeled moieties for various applications. Three guanine-based SNAPTag ligands ([18F]FBBG, [18F]pFBG and [18F]mFBG) were synthesized in high yields and were (radio)chemically characterized. HEK293 cells were engineered to express the SNAPTag on the cell surface and served as cell model to assess target affinity by radiotracer uptake assays, Western blotting and SDS-PAGE autoradiography. A subcutaneous HEK293-SNAPTag xenograft model in immunodeficient mice was used for in vivo evaluation of [18F]FBBG amd [18F]pFBG while the biodistribution of [18F]mFBG was characterized in naïve animals. The results were validated by ex vivo biodistribution studies and immunofluorescence staining of the xenografts. All three radiotracers were produced in high radiochemical purity, molar activity and good yields. Western blot analysis revealed successful SNAPTag expression by the transfected HEK293 cells. In vitro testing revealed high target affinity of all three tracers with an up to 191-fold higher signal in the HEK293-SNAPTag cells compared to untransfected cells. This was further supported by a prominent radioactive protein band at the expected size in the SDS-PAGE autoradiograph of cells incubated with [18F]FBBG or [18F]pFBG. The in vivo studies demonstrated high uptake in HEK293-SNAP xenografts compared to HEK293 xenografts with excellent tumor-to-muscle ratios (7.5 ± 4.2 for [18F]FBBG and 10.6 ± 6.2 for [18F]pFBG). In contrast to [18F]pFBG and its chemical analogue [18F]mFBG, [18F]FBBG showed no signs of unspecific bone uptake and defluorination in vivo. Radiolabeled SNAPTag ligands bear great potential for clinical applications such as in vivo tracking of cell populations, antibody fragments and targeted radiotherapy. With excellent target affinity, good stability, and low non-specific binding, [18F]FBBG is a highly promising candidate for further preclinical evaluation.

The application of smartphone-based color evaluation of passive sampling devices for gases has only been sparsely reported. The present review aims to compile available publications with respect to the configuration of the passive samplers, conditions of smartphone photographing, analytical procedure for color detection and quantification (including calibration processes), and their application to different target gases. The performance of the methods - whenever available - is presented regarding the analytical specifications selectivity, sensitivity, and limit of detection in comparison with other color evaluation methods of passive samplers. Practical aspects like requirements of instrumentation and ease of use will be outlined in view of the potential employment in education and citizen science projects. In one section of the review the inconsistent terminology of passive and diffusive sampling is discussed in order to clarify the distinction of information obtained from the uptake of the passive samplers between gas-phase concentration and the accumulated deposition flux of gaseous analytes. Colorimetric gas sensors are included in the review when applied in passive sampling configurations and evaluation is performed with smartphone-based color evaluation. Differences in the analytical procedures employed after the passive sampling step and prior to the detection of the colored compounds are also presented.

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

Ship detection from synthetic aperture radar (SAR) imagery is crucial for various fields in real-world applications. Numerous deep learning-based detectors have been investigated for SAR ship detection, which require a substantial amount of labeled data for training. However, SAR data annotation is time-consuming and demands specialized expertise, resulting in that deep learning-based SAR ship detectors struggle due to a lack of annotations. With limited labeled data, semi-supervised learning is a popular approach for boosting detection performance by excavating valuable information from unlabeled data. In this paper, a semi-supervised SAR ship detection network is proposed, termed as Multi-Teacher Dempster-Shafer Evidence Fusion Net-work (MTDSEFN). The MTDSEFN is an enhanced framework based on the basic teacher-student skeleton frame, comprising two branches: the Teacher Group (TG) and the Agency Teacher (AT). The TG utilizes multiple teachers to generate pseudo-labels for different augmentation versions of unlabeled samples, which are then refined to obtain high-quality pseudo-labels by using Dempster-Shafer (D-S) fusion. The AT not only serves to deliver weights of its own teacher to the TG at the end of each epoch, but also updates its own weights after each iteration, enabling the model to effectively learn rich information from unlabeled data. The combination of TG and AT guarantees both reliable pseudo-label generation and learning comprehensive diversity information from numerous unlabeled samples. Extensive experiments were performed on two public SAR ship datasets, and the results demonstrated the effectiveness and superiority of the proposed approach.

The nuclear hormone family of receptors regulates gene expression. The androgen receptor (AR) shuttles upon ligand binding and homodimerization from the cytosol into the nucleus to activate gene expression. Thyroid hormone receptors(TR), retinoic acid receptors (RAR), and the vitamin D receptor (VDR) are present in the nucleus bound to chromatin as a heterodimer with the retinoid X receptors (RXR) and repress gene expression. Ligand binding leads to transcription activation. The hormonal ligands for these receptors play crucial roles to ensure the proper conduct of very many tissues and exert effects on prostate cancer (PCa) cells. Androgens support PCa proliferation and deprivation alone or with chemotherapy is the standard therapy for PCa. RAR activation and 3,5,3'-triiodo-L-thyronine (T3) stimulation of TR support the growth of PCa cells. Ligand stimulation of VDR drives growth arrest, differentiation, and apoptosis of PCa cells. Often these receptors are explored as separate avenues to find treatments for PCa and other cancers. However, there is accumulating evidence to support receptor interactions and crosstalk of regulatory events whereby a better understanding might lead to new combinatorial treatments.

For very first time, we report the synthesis of 8-(2-methoxyphenyl)-6-methyl-2-(1-methyl-1H-benzo[d]imidazol-2-yl)quinoline 1. This was achieved in several steps, including usage of Suzuki reaction for functionalization of 2-(1H-benzo[d]imidazol-2-yl)quinoline moiety. The new compound exhibits blue fluorescence. Its structure was confirmed with 1D- and 2D-NMR spectroscopy, IR-spectroscopy, high-resolution mass spectrometry and X-ray analysis.

This research aims to apply Artificial Intelligence (AI) methods, specifically Artificial Immune Systems (AIS), to design an optimal control strategy for a multivariable control plant. Two specific industrial control approaches are investigated: I-PD (Integral-Proportional Derivative) and PI-D (Proportional-Integral Derivative) control. The motivation for using these variations of PID controllers is that they are functionally implemented in modern industrial controllers, where they provide precise process control. The research results in a novel solution to the control synthesis problem for the industrial system. In particular, the research deals with the synthesis of I-P control for a two-loop system in the technological process of a distillation column. This synthesis is carried out using the AIS algorithm, which is the first application of this technique in this specific context. Methodological approaches are proposed to improve the performance of industrial multivariable control systems by effectively using optimization algorithms and establishing modified quality criteria. The numerical performance index ISE justifies the effectiveness of the AIS-based controllers in comparison with conventional PID controllers (ISE₁ = 1.865, ISE₂ = 1.56). The problem of synthesis of the multi-input multi-output (MIMO) control system is solved, considering the interconnections due to the decoupling procedure.

This is a single tertiary center in southwest Romania, population-based, study. We retrospectively compared data obtained in two periods: January 2008 - December 2013 and January 2018 - De-cember 2023, respectively. The global incidence of transposition of great arteries (TGA) - the ter-minated cases added to the ones resulting in live-born pregnancies, remained almost constant. The live-born incidence of TGA decreased (0.34% to 0.013%). The prenatal detection rate increased slightly (71.42% to 87.5%). The median gestational age at the diagnosis decreased, from 29.3 ges-tational weeks (mean 25.4) to 13.4 weeks (mean 17.2). The proportion of terminated pregnancies significantly increased (14.28% to 75%, p = 0.019).

The celebrated geodesic congruence equation of Raychaudhuri, together with the resulting singularity theorems of Penrose and Hawking that it enabled, yield a highly general set of conditions under which a spacetime (or, more generically, a pseudo-Riemannian manifold) is expected to become geodesically incomplete. However, the proofs of these theorems traditionally depend upon a collection of assumptions about the continuum spacetime (and, in the physical case, the stress-energy distribution defined over it), including its global structure, its energy conditions, the existence of trapped null surfaces and the various volume/intersection properties of geodesic congruences, that are inherently difficult to translate to the case of discrete spacetime formalisms, such as causal set theory or the Wolfram model. Some, such as the discrete analog of Raychaudhuri's equation for the volumes of geodesic congruences, are subtle to formulate due to intrinsic differences in the behavior of discrete vs. continuous geodesics; for others, such as the definition of a trapped null surface, no appropriate translation is known for the general discrete case due to a lack of a priori coordinate information. It is therefore a non-trivial question to ask whether (and to what extent) there exist equivalently general conditions under which one expects discrete spacetimes to become geodesically incomplete, and how these conditions might differ from those in the continuum. This article builds upon previous work, in which the conformal and covariant Z4 (CCZ4) formulation of the Cauchy problem for the Einstein field equations, with constraint-violation damping, was defined in terms of Wolfram model evolution over discrete (spatial) hypergraphs for the case of vacuum spacetimes, and proceeds to consider a minimal extension to the non-vacuum case by introducing a massive scalar field distribution, defined in either spherical or axial symmetry. Under appropriate assumptions, this scalar field distribution admits a physical interpretation as a collapsing (and, in the axially-symmetric case, uniformly rotating) dust, and we are able to show, through a combination of rigorous mathematical analysis and explicit numerical simulation, that the resulting discrete spacetimes converge asymptotically to either non-rotating Schwarzschild black hole solutions or maximally-rotating (extremal) Kerr black hole solutions, respectively. Although the assumptions used in obtaining these preliminary results are very strong, they nevertheless offer hope that a more general, perhaps ultimately ``Penrose-like'', singularity theorem may be provable in the discrete spacetime case too.

We study the problem of a spherically-symmetric distribution of a perfect relativistic fluid accreting onto a (potentially spinning) black hole within a fully discrete spacetime setting. This problem has previously been studied extensively in the context of continuum spacetimes, beginning with the purely analytic work of Bondi in the spherically-symmetric Newtonian case, Michel in the spherically-symmetric general relativistic case, and Petrich, Shapiro and Teukolsky in the axially-symmetric general relativistic case relevant for spinning black holes. However, the purpose of the present work is to determine the effect of discretization of the underlying spacetime upon the mass/energy and momentum accretion rates, the overall morphology and characteristics of the accretion flow, and the drag force exerted on the black hole in the case of non-zero spin. In order to achieve this, we first develop a novel formulation of the equations of general relativistic hydrodynamics that is more directly amenable to rigorous analysis within a discrete spacetime setting, and we then proceed to implement this formulation into the \textsc{Gravitas} computational general relativity framework. Through a combination of mathematical analysis and explicit numerical simulation in \textsc{Gravitas}, we discover that the mass/energy and momentum accretion rates both decrease monotonically as functions of the underlying spacetime discretization scale, with this effect becoming more pronounced for higher values of the black hole spin parameter, higher fluid temperatures, and stiffer equation of state parameters. We also find that the exerted drag force is highly sensitive to the value of the underlying discretization scale in the case of spinning black hole spacetimes, with certain instabilities becoming significantly more pronounced at certain critical values of the discretization parameter. We discuss some potentially observable consequences of these results, as well as some directions for future theoretical investigation.

This is the second in a series of two articles introducing the Gravitas computational general relativity framework, in which we now focus upon the design and capabilities of Gravitas's numerical subsystem, including its ability to perform general 3+1 decompositions of spacetime via the ADM formalism, its support for the definition and construction of arbitrary Cauchy surfaces as initial data, its support for the definition and enforcement of arbitrary gauge and coordinate conditions, its various algorithms for ensuring the satisfaction of the ADM Hamiltonian and momentum constraints, and its unique (totally-unstructured) adaptive refinement algorithms based on hypergraph rewriting via Wolfram model evolution. Particular attention will be paid to the seamless integration between Gravitas's symbolic and numerical subsystems, its ability to configure, run, analyze and visualize complex numerical relativity simulations and their outputs within a single notebook environment, and its capabilities for handling generic curvilinear coordinate systems and spacetimes with general (and often highly non-trivial) topologies using its specialized and highly efficient hypergraph-based numerical algorithms. We also provide illustrations of Gravitas's functionality for the visualization of hypergraph geometries and spacetime embedding diagrams in two and three dimensions, the ability for Gravitas's symbolic and numerical subsystems to be used in concert for the extraction of gravitational wave signals and other crucial simulation data, and Gravitas's in-built library of standard initial data, matter distributions and gauge conditions. We conclude by demonstrating how the numerical subsystem can be used to set up, run, visualize and analyze a standard yet nevertheless reasonably challenging numerical relativity test case: a binary black hole collision and merger within a vacuum spacetime (including the extraction of its outgoing gravitational wave profile).

Optical biopsy describes a range of medical procedures in which light is used to investigate disease in the body, often in hard-to-reach regions via optical fibres. Optical biopsies can reveal a multitude of diagnostic information to aid therapeutic diagnosis and treatment with higher specificity and shorter delay than traditional surgical techniques. One specific type of optical biopsy relies on Raman spectroscopy to differentiate tissue types at the molecular level and has been used successfully to stage cancer. However, complex micro-optical systems are usually needed at the distal-end to optimise the signal-to-noise properties of the Raman signal collected. Manufacturing these devices remains a critical challenge, particularly in a way suitable for large scale adoption. In this paper, we describe a novel fibre-fed micro-optic system designed for efficient signal delivery and collection during a Raman spectroscopy based optical biopsy. Crucially, we fabricate the device using a direct-laser-writing technique known as ultrafast laser assisted etching which is scalable and allows components to be aligned passively. The Raman probe has a sub-millimetre diameter and offers confocal signal collection with 71.3 ± 1.5% collection efficiency over a 0.8 numerical aperture. Proof of concept spectral measurements were performed on mouse intestinal tissue and compared with results obtained using a commercial Raman microscope.

Congestive heart failure (CHF) is a major cause of morbidity and mortality with an increasing prevalence in human and canine populations. Similar to humans, overactivation of the renin-angiotensin aldosterone system is involved in the pathophysiology of CHF in dogs. Current therapeutic strategies for the management of canine CHF include the use of RAAS inhibitors, diuretics and inodilators. The present review summarizes data from our own research on the modulation of the renin-angiotensin cascade in dogs in dogs, together with new findings (including novel therapeutic targets) from the veterinary and the human literature.

Recent studies have demonstrated a relationship between poor vitamin D status and respiratory infections and diarrhea among young children. Acute lower respiratory infections (ALRI) and diarrhea are among the two most important causes of death in under-5 children. In this analysis, we examine the extent to which vitamin-D deficiency (<10 ng/ml) predicts these outcomes using data from a randomized controlled trial (RCT) of daily folic acid and/ or vitamin B12 supplementation for six months in 6 to 30 months old children conducted in Delhi, India. Of the 960 subjects who had vitamin-D concentrations measured, 331(34.5%) were vitamin-D deficient. We found, after controlling for relevant potential confounders (age, sex, breastfeeding status, wasting, stunting, underweight, anemia status at base line and season), the risk of ALRI was significantly higher among vitamin-D deficient (OR 1.26; 95% CI: 1.03 to 1.55) compared to vitamin-D-replete children in the six months follow-up period. Vitamin-D status was not significantly associated with episodes of diarrhea and clinical pneumonia. The extent of causal relationship of vitamin-D status and ALRI needs to be explored in further studies.

Soil bacteria drive key ecosystem functions, including nutrient mobilization, soil aggregation and crop bioprotection against pathogens. Bacterial diversity is thus considered a key component of soil health. Conventional agriculture reduces bacterial diversity in many ways. Compost tea has been suggested as a bioinoculant that may restore bacterial community diversity and promote crop performance under conventional agriculture. Here, we conducted a field experiment to test this hypothesis in a soybean-maize rotation. Compost tea application had no influence on bacterial diversity or community structure. Plant growth and yield were also unresponsive to compost tea application. Combined, our results suggest that our compost tea bacteria did not thrive in the soil, and that the positive impacts of compost tea applications reported elsewhere may be caused by different microbial groups (e.g., fungi, protists, nematodes) or by abiotic effects on soil (e.g., contribution of nutrients and dissolved organic matter). Further investigations are needed to elucidate the mechanisms through which compost tea influences crop performance.

Over the last decades, in addition to the improvement of pathophysiological knowledge regarding the role and mechanisms of action of Vitamin D, there has been a progressive advancement in analytical technologies for its determination, as well as in methodological standardization. A significant number of scientific works, meta-analyses, and guidelines have been published on the importance of Vitamin D and the need for supplementation in deficient individuals. However, it appears necessary to clarify the fundamental elements related to the determination of Vitamin D (both at the strictly analytical and post-analytical levels) and the scientific evidence related to the efficacy/safety of supplementation. Additionally, given the important interrelations between Vitamin D, parathyroid hormone (PTH), and fibroblast growth factor-23 (FGF23), the analytical issues and clinical utility of these biomarkers will be discussed.

Although vitamin D deficiency has been correlated with an increased risk of cardiovascular disease (CVD), there are few data on the association between 25-hydroxyvitamin D (25(OH) D) and atherogenic indices predictive of CVD. This study aimed to investigate the relationship of vitamin D status with lipid profile and atherogenic indices in adult women in Morocco. Three hundred healthy women, aged 18 to 50 years, from Meknes were included. Fasting 25(OH) D and lipid concentrations were determined using a one-step electrochemiluminescence-based immunoassay and an enzymatic method, respectively. Atherogenic indices (Atherogenic index of plasma (AIP), non-HDL cholesterol (Non-HDL-C), Atherogenic coefficient (AC), Castelli risk indices I and II (CRI-I and II), and CHOLIndex (CI)) were calculated using conventional lipid parameters. Logistic regression models and operating characteristic curve (ROC) analysis were used to assess the relationship of the variables and estimate the threshold of 25(OH) D levels associated with high atherogenic indices. 25(OH) D below 20 ng/ml was significantly associated with an enhanced risk of hypertriglyceridemia and elevated values of AIP, AC, Non-HDL-C, and CRI-I with an OR (95% CI) of 4.904 (1.856-12.959); 3.637(2.149-6.158); 3.589(1.673-7.700); 2.074(1.215-3.540), and 2.481(1.481-4.123), respectively. According to ROC analysis, the likelihood of hypertriglyceridemia and high values of AIP, AC, Non-HDL-C, and CRI-I were associated with 25(OH)D thresholds ≤15.15 ng/ml, ≤ 17.5 ng/ml, ≤ 19.8 ng/ml, ≤ 20.1 ng/ml and ≤ 19.5 ng/ml, respectively, all p &lt; 0.01. Based on atherogenic indices, this study indicates that vitamin D below 20 ng/ml may increase the risk of cardiovascular disease in adult women. Additional health efforts are needed to raise awareness among women and healthcare providers in preventing and controlling cardiovascular risk factors.

We propose a novel transfer learning method for speech emotion recognition allowing us to obtain promising results when only few training data is available. With as low as 125 examples per emotion class, we were able to reach a higher accuracy than a strong baseline trained on 8 times more data. Our method leverages knowledge contained in pre-trained speech representations extracted from models trained on a more general self-supervised task which doesn’t require human annotations, such as the wav2vec model. We provide detailed insights on the benefits of our approach by varying the training data size, which can help labeling teams to work more efficiently. We compare performance with other popular methods on the IEMOCAP dataset, a well-benchmarked dataset among the Speech Emotion Recognition (SER) research community. Furthermore, we demonstrate that results can be greatly improved by combining acoustic and linguistic knowledge from transfer learning. We align acoustic pre-trained representations with semantic representations from the BERT model through an attention-based recurrent neural network. Performance improves significantly when combining both modalities and scales with the amount of data. When trained on the full IEMOCAP dataset, we reach a new state-of-the-art of 73.9% unweighted accuracy (UA).

Current sampling methods for detecting the presence of the invasive freshwater hydrozoan Craspedacusta sowerbii rely mainly on visual confirmation of the medusa stage. Confirming the presence of the polyp stage is equally important to observing medusae since typical late summer/early fall occurrences or observations of medusae are sporadic though becoming more frequent. The polyp stage is important as it is the organism’s primary stage and is present throughout the year depending on water temperatures. Therefore, sampling methods for the polyp stage are commonly the collection of substrates such as rocks, plants or pieces of wood in a given body of water and can be cumbersome to examine. Based on preliminary culturing of the polyp stage on glass and plastic microscope slides in the lab, we designed a novel sampling methodology based on submerging 4 substrate types (small glass petri dishes, Hester-Dendy plates, plastic and glass microscope slides) to confirm the presence of C. sowerbii polyps in the field. We tested this method in various lakes in the Illinois-Indiana region (USA). The sampling method we designed was effective in that C. sowerbii polyps (and sometimes colonies) were found on both plastic and glass slides. While this method can be sufficient for detection of the polyp stage, it also shows significant potential for improvement; we highlight water flow and competition and predation from other organisms as significant factors influencing the collection of C. sowerbii polyps for future methodologies.

This article serves as a preliminary introduction to the design of a new, open-source applied and computational category theory framework, named Categorica, built on top of the Wolfram Language. Categorica allows one to configure and manipulate abstract quivers, categories, groupoids, diagrams, functors and natural transformations, and to perform a vast array of automated abstract algebraic computations using (arbitrary combinations of) the above structures; to manipulate and abstractly reason about arbitrary universal properties, including products, coproducts, pullbacks, pushouts, limits and colimits; and to manipulate, visualize and compute with strict (symmetric) monoidal categories, including full support for automated string diagram rewriting and diagrammatic theorem-proving. In so doing, Categorica combines the capabilities of an abstract computer algebra framework (thus allowing one to compute directly with epimorphisms, monomorphisms, retractions, sections, spans, cospans, fibrations, etc.) with those of a powerful automated theorem-proving system (thus allowing one to convert universal properties and other abstract constructions into (higher-order) equational logic statements that can be reasoned about and proved using standard automated theorem-proving methods, as well as to prove category-theoretic statements directly using purely diagrammatic methods). Internally, Categorica relies upon state-of-the-art graph and hypergraph rewriting algorithms for its automated reasoning capabilities, and is able to convert seamlessly between diagrammatic/combinatorial reasoning on labeled graph representations and symbolic/abstract reasoning on underlying algebraic representations of all category-theoretic concepts. In this first of two articles introducing the design of the framework, we shall focus principally upon its handling of quivers, categories, diagrams, groupoids, functors and natural transformations, including demonstrations of both its algebraic manipulation and theorem-proving capabilities in each case.

A dendrochronological investigation was undertaken on subfossil Scots pine (Pinus sylvestris L.) stumps following their discovered during conservation management activities at Wem Moss, a small (28ha) former raised mire in Shropshire, UK. Two ring-width chronologies were constructed from 14 of the 17 trees investigated spanning 198 and 208 years respectively. Whilst absolute dating was not possible, radiocarbon assays provided an estimated age for this mire-rooting woodland of between 3015 – 2505 years Cal BC, coinciding with the age traditionally associated with the widespread mortality of pine trees throughout much of the UK and Ireland, The Pine Decline (circa 4 ka radiocarbon years BP). Placed in a wider geographical context, the Wem Moss pines are located within the wider lowland area of the Meres and Mosses Region, where previous studies on subfossil pine have demonstrated protracted declines in mire-rooting trees. These have included tree mortality significantly post-dating The Pine Decline, notably at larger peatland sites exceeding 5.5 km2. This macrofossil evidence for the presence of Scots pine into the late Holocene is supported by continuous Pinus pollen representation at peatland sites in the Welsh Marches (English-Welsh border) suggesting the possible survival of native Scots pine trees in this area up to the present-day. This research highlights the incomplete and patchy nature of palaeo-vegetational records and also the potential for genetic research on living Scots pine in possible refugial areas in the UK and Ireland.

External stressors strongly increase cardiovascular activity and induce metabolic changes that ensure the availability of glucose and oxygen as part of a co-ordinated stress response. Exposure to stress during early life appears to have an exaggerated long-term effect on this response, leading to an increased risk or cardiometabolic disorders. Here we demonstrate that acute stress induced glucose release is impacted by the early life environment in rodent maternal deprivation and early-life infection models and this was validated in our EpiPath human early-life adversity cohort. In all three models differences in baseline blood glucose levels after ELA exposure were sex dependent. The human ELA model showed higher levels of basal glucose in females, similar to the mouse infection and rat maternal deprivation models. We anticipated that the stress induced glucose rise would be a GC dependent process. However, the kinetics of stress-induced glucose release, peaking 15-28 minutes before cortisol suggest that it is a GC-independent process. We confirmed this by administering an escalating dose of cortisol to a health human cohort, and the inability of an intravenous GC bolus induce a glucose rise in man confirms that it is a rapid, GC independent, process.In conclusion, we provide a novel perspective on the mechanisms behind stress related metabolic changes and highlights the importance of collecting early life data as a measure to understand an individual’s metabolic status in a better light.

Hashimoto's thyroiditis (HT) is essentially featured by self-tissue destruction by means of the adaptive immune responses that evade immune regulation. Vitamin D carries out an immunomodulatory role that appears to promote immune tolerance. The aim of this study is to elaborate a narrative review about the relationship between vitamin D status and HT and the role of vitamin D supplementation to reduce HT risk by modulating the immune system. There is an extensive literature confirming that vitamin D levels are significantly lower in HT patients compared to healthy people. On the other hand, after the supplementation with cholecalciferol in patients with HT and vitamin D deficiency, thyroid autoantibody titer decreased significantly, However, there are no conclusive results on the effect of vitamin D supplementation on the thyroid function. The confirmation of the beneficial effects of vitamin D in the prevention and treatment of autoimmune thyroid diseases require additional randomized, double-blind, placebo-controlled trials with longer follow-up.

Similar to humans, the renin-angiotensin-aldosterone system (RAAS) plays a key role in regulating blood pressure and body fluid homeostasis in dogs and cats. The classical RAAS pathway, which involves the conversion of angiotensin I to angiotensin II by the angiotensin converting enzyme (ACE), leads to aldosterone production and associated maladaptive effects in cardiovascular and renal diseases. Recent studies have highlighted the alternative RAAS pathway, which counteracts these effects through angiotensin 1-7, promoting vasodilation and reducing inflammation. Beyond RAAS modulation, RAAS inhibitors have been shown to exert significant anti-inflammatory properties. This is particularly relevant given the American Heart Association's recent focus on Cardiovascular-Kidney-Metabolic (CKM) health, which emphasizes the interconnected risks of cardiovascular disease, chronic kidney disease (CKD), type 2 diabetes, and obesity. These conditions share common pathophysiological pathways, including chronic inflammation, oxidative stress, and metabolic dysregulation. Advances in biomedical research, including the development of adult stem cell-derived canine organoids, provide impetus to study the effects of RAAS modulators and new CVD drugs on CKM health, with a focus on epithelial inflammation within the context of One Health.

This paper aims to demonstrate that, beyond the small world of Riemann-Liouville and Caputo derivatives, there is a vast and rich world with many derivatives suitable for specific problems and various theoretical frameworks to develop, corresponding to the different paths taken. Notions of time and scale sequences are introduced and general associated basic derivatives, namely right/stretching and left/shrinking, are defined. A general framework for fractional derivative definitions is reviewed and applied to get both known and new fractional order derivatives. Several fractional derivatives are considered, mainly: Liouville, Hadamard, Euler, bilinear, tempered, q-derivative, and Hahn.

Alcoholic liver disease (ALD) develops when the immunotolerant environment of the liver is compromised due to excessive alcohol consumption. ALD progression involves variations in the expression of multiple genes, resulting in liver inflammation and the development of a leaky gut. Molecular mechanism involved for ALD progression is still unclear, and due to that there are currently no FDA-approved drugs available for its treatment. In this study, the protective effects of Graphene oxide nanoparticles (GO) was investigated against ethanol-induced damage in the gut-liver axis in in vitro. GO was synthesized using a modified Hummer's method and characterization was done. Given the general concerns regarding nanoparticle toxicity, assessment of cell viability, lipid accumulation, DNA damage, cell death, and the generation of reactive oxygen species (ROS) were conducted using various techniques. Furthermore, gene expression of pro- and anti-inflammatory cytokines was done using RT-qPCR. The findings revealed that GOs promoted cell viability even against ethanol treatment. Additionally, lipid accumulation significantly decreased when cells were treated with GO alongside ethanol compared to ethanol treatment alone, with similar trends observed for other assays. Gene expression analysis indicated that GO treatment reduced the expression of proinflammatory cytokines while enhancing the expression of antioxidant genes. Moreover, GO treatment led to improvements in gut permeability and a reduction in proinflammatory cytokines in colon cells damaged by ethanol. These findings suggest that GO holds promise as a drug carrier, exhibiting no observed toxic effects. By shedding light on the protective effects of GO against ethanol-induced damage, this study contributes to the burgeoning field of nanoparticle-mediated therapy for ALD.

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

Short-range Internet of Things (IoT) sensor nodes operating at 2.4 GHz need to provide ubiquitous wireless sensor networks (WSNs) with energy-efficient, wide-range output power (POUT) and fully integrated on a single chip for wireless body area networks (WBANs) and wireless personal area networks (WPANs) using low-power Bluetooth (BLE) and Zigbee standards. The proposed fully integrated transmitter (TX) utilizes a digitally controllable current-mode class-D (CMCD) power amplifier (PA) with a second harmonic distortion (HD2) suppression to reduce VCO pulling in an integrated system while meeting harmonic limit regulations. The CMCD PA is divided into 7-bit slices that can be reconfigured between differential and single-ended topologies. Duty cycle distortion compensation is performed for HD2 suppression, and an HD2 rejection filter and a modified C-L-C low-pass filter (LPF) reduce HD2 further. Implemented in a 28 nm CMOS process, the TX achieves a wide POUT range of from 12.1 to -31 dBm and provides a maximum efficiency of 39.8% while consuming 41.1 mW at 12.1 dBm POUT. The calibrated HD2 level is -82.2 dBc at 9.93 dBm POUT, resulting in a transmitter figure of merit (TX_FoM) of -97.52 dB. Higher order harmonic levels remain below -41.2 dBm even at 12.1 dBm POUT, meeting regulatory requirements.

Chronic kidney disease (CKD) and cardiovascular disease (CVD) are highly prevalent conditions, each significantly contributing to the global burden of morbidity and mortality. CVD and CKD share a great number of common risk factor, such as hypertension, diabetes, obesity, and smoking among others. Their relationship extends beyond these factors, encompassing intricate interplay between the two systems. Within this complex network of pathophysiological processes, vitamin D has emerged as a potential linchpin, exerting influence over diverse physiological pathways implicated in both CKD and CVD. In recent years, scientific exploration has unveiled a close connection between these two prevalent conditions and vitamin D, a crucial hormone traditionally recognized for its role in bone health. This article aims to provide an extensive review of vitamin D's multifaceted and expanding actions concerning its involvement in CKD and CVD.

A continuous spatio-temporal database of accurate soil moisture (SM) measurements is an important asset for agricultural activities, hydrologic studies, and environmental monitoring. The Advanced Microwave Scanning Radiometer 2 (AMSR2), launched in May 2012, has been providing SM data globally with a revisit period of two days. It is imperative to assess the quality of this data before performing any application. Since resources of accurate SM measurements are very limited in Puerto Rico, this research will assess the quality of the AMSR2 data by comparing with ground-based measurements and perform a downscaling technique to provide a better description of how the sensor perceives the surface soil moisture as it passes over the island. The comparison consisted of the evaluation of the mean error, root mean squared error, and the correlation coefficient. Two downscaling techniques were used and their performances were studied. The results revealed that AMSR2 products tend to underestimate. This is due to the extreme heterogeneous distributions of elevations, vegetation densities, soil types, and weather events on the island. This research provides a comprehensive study on the accuracy and potential of the AMSR2 products over Puerto Rico. Further studies are recommended to improve the AMSR2 products.

Article explores participant specific study of muscle inherehit dynamics hidden inside the diognostic electromyography (D-EMG) signals during load pull exercises, aiming to uncover underlying patterns and nonlinear behaviors. Employing a multi-step analytical framework, the study first evaluates signal stationarity through Quantile-Quantile (Q-Q) plot and surrogate data analyses, revealing insights into signal stability. Subsequent use of phase space reconstruction techniques exposes intrinsic dynamics within the EMG signals, visualized through Poincar´e maps, elucidating attractor geometry and system dynamics. Histogram analysis further dissects the Poincar´e maps, offering insights into signal behavior relative to physiological processes. Additionally, the study quantifies the largest Lyapunov exponent from the Poincar´e maps, providing a measure of dynamical complexity within the muscle EMG signals during load pull exercises. By integrating these methods, this research sheds light on the nuanced interplay between EMG signals and muscle activity during dynamic exercises, offering valuable insights for rehabilitation strategies.

Dengue infection is one of the most important vector-borne diseases worldwide and is a significant public health problem in the tropics. Mosquito control continues to be the primary approach to reducing the disease burden and the dengue virus (DENV) spread. Aside from the traditional larviciding and adulticiding interventions, autodissemination using pyriproxyfen-treated (AD-PPF) ovitraps is one of the promising methods to complement existing vector control strategies. Our paper assessed the efficacy of AD-PPF in reducing DENV infection in two barangays in Parañaque City. Using saliva samples from the participants from both the control and intervention sites, we collected the seroprevalence data for three months in each of the two years. Spatial analysis was conducted to determine hotspot areas and identify DENV infection distributions across the trial periods. Results showed that the intervention site was identified as having clustering of DENV infection in Month 0 of Year 1 and shifted to random dispersion of dengue cases at the end of Month 3 in Year 2. The disappearance of the clustering of the intervention site translates to a decrease in the cases of DENV infection relative to the control site. Furthermore, we also identified that DENV infection transmission occurs at a small-scale level that did not go beyond 86 meters. In conclusion, AD-PPF is suggested to be an effective strategy and may be used as an additional vector control approach, albeit in its short-term implementation.

This paper looks at key elements of global culture that are driving a new paradigm shift in museums causing them to question their raison d'être, their design and physical space, recognizing the need to accommodate visitor interaction and participation, and to reprioritize institutional outcomes and goals reexamining their priorities. As heritage sharing in online spaces reaches across national, political, and social boundaries on platforms and networks, this has been driven by museum engagement with Internet life during the pandemic. Museum relationships and interactions with communities both local and global, continue to challenge core values and precepts, leading to radical changes in how museums define their roles and responsibilities. In this new cultural landscape, museums are responding to human digital identity in a tidal wave of human interactions on the Internet, from social media to online sharing of images and videos. This is revealing shared perspectives on cultural conflict as being tied to freedom of expression of one’s heritage embedded in digital identity.

Aseptic implant loosening after total joint replacement is partially influenced by material-specific factors when cobalt-chromium alloys are used, including osteolysis induced by wear- and corrosion products, and stress shielding. Here, we aim to characterize a hybrid material consisting of alumina-toughened zirconia ceramics (ATZ) and additively manufactured Ti-35Nb-6Ta (TiNbTa), joined by a glass solder. The structure of the joint, static and fatigue shear strength, the influence of accelerated aging, and the cytotoxicity using an elution assay with human osteoblasts is characterized. Furthermore, the biomechanical properties of functional demonstrators of a femoral component for total knee replacements are evaluated. TiNbTa-ATZ specimens showed a homogenous joint with statistical distributed micro-pores and a slight accumulation of Al-rich compounds at the glass solder-TiNbTa interface. The static shear strength was 26.4 ± 4.2 MPa (Ti-ATZ reference: 38.2 ± 14.4 MPa, p = 0.117), all specimens survived 107 cycles of shear loading to 10 MPa, and aging did not reduce the strength. TiNbTa-ATZ did not impair the proliferation and metabolic activity of human osteoblasts. Functional demonstrators of TiNbTa-ATZ provided a maximum bearable extension-flexion moment of 40.7 ± 2.2 Nm. Biomechanical and biological properties of TiNbTa-ATZ demonstrate potential application for endoprosthetic implants.

OPMDs (Oral Potentially Malignant Disorders) are a group of disorders affecting the oral mucosa that are characterized by aberrant cell proliferation and a higher risk of malignant transformation. Vitamin D (VitD) and its receptor (VDR) have been extensively studied for their potential contributions to the prevention and therapeutic management of a range of diseases and neoplastic conditions, including oral cancer. Observational studies suggest correlations between VitD deficiency and higher cancer risk, worse prognosis, and increased mortality rates. Interestingly, emerging data also reveals a link between VitD insufficiency and the onset or progression of OPMDs. Understanding the role of the VitD-VDR axis not only in established oral tumors but also in OPMDs might thus enable early detection and prevention of malignant transformation. With this article, we want to provide an overview of current knowledge about OPMDs and VitD, and investigate their potential association and ramifications for clinical management of OPMDs.

In the present work we revise and extend the Characteristic Crystallographic Element (CCE) norm, an algorithm used to simultaneously detect radial and orientational similarity of computer-generated structures with respect to specific reference crystals and local symmetries. Based on the identification of point group symmetry elements, the CCE descriptor is able to gauge local structure with high precision and finely distinguish between competing morphologies. As test cases we use computer-generated monomeric and polymer systems of spherical particles interacting with the hard-sphere and square-well attractive potentials. We demonstrate that the CCE norm is able to detect and differentiate, between others, among: hexagonal close packed (HCP), face centered cubic (FCC), hexagonal (HEX) and body centered cubic (BCC) crystals as well as non-crystallographic fivefold (FIV) local symmetry in bulk 3-D systems; triangular (TRI), square (SQU) and honeycomb (HON) crystals, as well as pentagonal (PEN) local symmetry in thin films of one-layer thickness (2-D systems). The descriptor is general and can be applied to identify the symmetry elements of any point group for arbitrary atomic or particulate system in two or three dimensions, in the bulk or under confinement.

Zika Virus (ZIKV) is a pathogenic member of the flavivirus family, with several unique charac-teristics. Unlike any other arbovirus, ZIKV can be transmitted sexually and maternally, and thus produce congenital syndromes (CZS) due to its neurotropism. This challenges the search for safe active molecules that can protect pregnant women and their fetuses. In this context, and in the ab-sence of any existing treatment, it seemed worthwhile to test whether the known cytoprotective properties of adiponectin and its pharmacological analog, AdipoRon, could influence the outcome of ZIKV infection. We showed that both AdipoRon and adiponectin could significantly reduce in vitro infection of A549 epithelial cells, a well-known cell model for flaviviruses infection studies. This effect was particularly observed when a pre-treatment was carried out. Conversely, ZIKV revealed an ability to down-regulate adiponectin receptor expression and thereby limit adi-ponectin signaling.

Museums increasingly recognize the need to address advances in digital culture which impact the expectations and needs of their audiences. Museum collections of real objects need to be presented both on their own premises and digitally online, especially as social media becomes more and more influential in people’s everyday lives. We investigate these challenges magnified by advances in digital and computational media and culture looking particularly at recent and relevant reports on changes in the ways museums interact with the public. We find that the Covid-19 pandemic has accelerated many of the changes driving museum transformation. We believe that museums must be more prepared than ever to adapt to unabated technological advances set in the midst of cultural and social revolution, now intrinsic to the digital landscape in which museums are inevitably connected and participating across the global digital ecosystem where they inevitably find themselves entrenched.

Urbanization affects all elements of the pre-urban environment, including soils, hydrology, vegetation, and microclimate. Recently, Saudi Arabia has experienced rapid urbanization and growth. Thus, the country's biodiversity has been threatened. In Riyadh, beetle assemblages were assessed along a rural-suburban-urban gradient. A total of 2,791 individuals from 94 species belonging to seven families were collected at 15 sites along three different gradients of urbanization in Wadi Hanifa. Tenebrionidae dominated abundance (60.1%) and richness (38%). Beetle abundance, evenness, and diversity were not different among habitats; however, species richness was higher in rural habitats. DCA and CCA analyses showed distinct differences among sites along gradients. Urbanization intensity, soil variables, and land cover were significantly correlated with DCA axis 1, while elevation and flora were significantly correlated with DCA axis 2. The most critical operating environmental variables in Wadi Hanifa were buildings, elevation, soil organic carbon, litter cover, and litter depth, as well as plants such as Launaea capitata, Lycium shawii, Alhagi graecorum, and Heliotropium currasavicum. Ten species in our study are associated with urban habitats, six with suburban habitats, and seven with rural habitats. Consequently, expanding urban areas may negatively affect the richness and composition of beetles and may result in the loss of some native species.

I extend earlier work that derived a Born rule for nuclear-decay cloud chamber tracks (Mott problem) without invoking quantum measurement axioms. The key ingredient there was the identification of sites at which the cross section for ionization by a passing charged particle is singular at ionization threshold. This singularity arose from a Penning-like process involving molecular polarization in sub-critical vapor clusters. In the present paper, I propose a simple experiment to determine if similar ionization physics takes place in the mica window of a Geiger counter and drives the collimation of spherically-symmetric wavefunctions outside the counter tube into ion tracks inside. The experiment measures the count rate from a radioactive point source as a function of source-window separation. I have performed a proof-of-concept of this experiment; results are consistent with the singular-ionization picture. I consider implications for the Stern-Gerlach experiment and superconducting qubits. I detail further work required to flesh out these results more rigorously.

Adrenarche is a developmental phase that occurs only in humans and chimpanzees. It is characterized by the maturation of the adrenal zona reticularis, culminating in the synthesis and secretion of enormous amounts of dehydroepiandro-sterone sulfate (DHEAS) into the blood stream. The purpose of adrenarche, and the flooding of the circulation with DHEAS in the period preceding the onset of adult human body size, has been described as “enigmatic.” This laboratory has uncovered a previously unknown, human-specific “kill-switch” tumor suppression mechanism in which circulating DHEAS is pumped into cells that have undergone tumorigenic mutation(s)— primarily in the TP53 tumor suppressor gene. We refer to such tumorigenic single cells as singularities. The advantage of eliminating tumorigenic cells while they are still in their single cell state, before they have evolved into the heterogeneous tumor cell populations that have proven refractory to chemotherapeutic sterilization, is obvious. This is accomplished by activation of the kill-switch in singularities by de-sulfating imported DHEAS to dehydroepiandrosterone (DHEA), a potent uncompetitive inhibitor of the enzyme Glucose-6-phosphate Dehydrogenase (G6PD). G6PD is responsible for the production of most of the NADPH required for the synthesis and maintenance of activity of anti-oxidant selenoproteins, and for the ubiquinol that prevents ferroptosis. In singularities, uncompetitive inhibition of G6PD by DHEA rapidly becomes irreversible, leading to ROS/ferroptosis-mediated cell death.

The nonlocality of entangled quantum mechanical systems is incompatible with the standard interpretation of special relativity as a single 4D Minkowskian metric spacetime. The difficulty is that the definition of a spacetime interval between any pair of events precludes any form of nonlocal interaction, even the relatively benign non-signaling correlations. By an application of the relativity principle, and the use of the space ←→ time symmetry of the Lorentz boost I propose here a reinterpretation of special relativistic spacetime. This new ontology consists of a set of coexisting 3+1D spaces (‘framespaces’), each containing unique content in the form of a complex density. These spaces are related by the Lorentz boost, and coupled pairwise in a manner dictated by the Lorentz transformation. The inter-space coupling acting on the spacetime content gives rise to a nonlocal wave phenomenon, which is identified as quantum wave mechanics. The interspace coupling strength is then inversely proportional to Planck’s constant. The coexistence of multiple spaces is interpreted as momentum superposition, implying that momentum is the fundamental physical basis of quantum superposition. This new spacetime interpretation of quantum mechanics has many consequences, including explanations of quantum non-locality, the spacetime role of Planck’s constant, quantum measurement as a symmetry-breaking process and the redundancy of description of gauge theory.

A four-parameter kinematic model for the position of a fluid parcel in a time-varying ellipse is introduced. For any ellipse advected by an arbitrary linear two-dimensional flow, the rates of change of the ellipse parameters are uniquely determined by the four parameters of the velocity gradient matrix, and vice-versa. This result, termed ellipse/flow equivalence, provides a stronger version of the well-known result that a linear velocity field maps an ellipse into another ellipse. Moreover, ellipse/flow equivalence is shown to be a manifestation of Stokes' theorem. This is done by deriving a matrix-valued relationship, called the geometric Stokes' theorem, that involves a spatial integral over the velocity gradient tensor, thus accounting for the two strain terms in addition to the divergence and vorticity. General expressions for various physical properties of an elliptical ring of fluid are also derived. The ellipse kinetic energy is found to be composed of three portions, associated respectively with the circulation, the rate of change of the moment of inertia, and the variance of parcel angular velocity around the ellipse. A particular innovation is the use of four matrices, termed the IJKL basis, that greatly facilitate the required calculations.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), an RNA virus, is responsible for coronavirus disease 2019 (COVID-19) pandemic of 2020. Experimental evidence suggests that microRNA can mediate an intracellular defence mechanism against some RNA viruses. The purpose of this study was to identify microRNA with predicted binding sites in the SARS-CoV-2 genome, compare these to their microRNA expression profiles in lung epithelial tissue and make inference towards possible roles for microRNA in mitigating coronavirus infection. We hypothesize that high expression of specific coronavirus-targeting microRNA in lung epithelia may protect against infection and viral propagation, conversely low expression may confer susceptibility to infection. We have identified 128 human microRNA with potential to target the SARS-CoV-2 genome, most of which have very low expression in lung epithelia. Six of these 128 microRNA are differentially expressed upon in vitro infection of SARS-CoV-2. Twenty-eight and 23 microRNA also target the SARS-CoV and MERS-CoV, respectively. In addition, 48 and 32 microRNA are commonly identified in two other studies. Further research into identifying bona fide coronavirus targeting microRNA will be useful in understanding the importance of microRNA as cellular defence mechanism against pathogenic coronavirus infections.

This study develops a hybrid machine learning (ML) algorithm integrated with IoT technology to improve the accuracy and efficiency of soil monitoring and tomato crop disease prediction in Anakapalle, a south Indian station. An IoT device collected one-minute and critical soil parameters—humidity, temperature, pH values, nitrogen (N), phosphorus (P), and potassium (K)—essential for assessing soil health and optimizing crop growth. Kendall's correlations were computed to rank these parameters for utilization in hybrid ML techniques. Various ML algorithms including K-Nearest Neighbors (KNN), Support Vector Machines (SVM), Decision Tree (DT), Random Forest (RF), and Logistic Regression (LR) were evaluated. A novel hybrid algorithm, 'Bayesian Optimization with KNN', was introduced to combine multiple ML techniques and enhance predictive performance. The hybrid algorithm demonstrated superior results with 95% accuracy, precision, and recall, and an F1 score of 94%, while individual ML algorithms achieved varying results: KNN (80% accuracy), SVM (82%), DT (77%), RF (80%), and LR (81%) with differing precision, recall, and F1 scores. This hybrid ML approach proved highly effective in predicting tomato crop diseases in natural environments, underscoring the synergistic benefits of IoT and advanced ML techniques in optimizing agricultural practices.

Soil CO2 efflux (FCO2) plays a dominant role in the terrestrial carbon (C) cycle but interpreting constraints on local observations is impeded by challenges in disentangling belowground CO2 sources. Trees contribute most C to forest soils, so linking aboveground properties to FCO2 could open new avenues to study plant-soil feedbacks and facilitate scaling; furthermore, FCO2 responds dynamically to meteorological conditions, complicating predictions of total FCO2 and forest C balance. We tested for proximity effects of individual Acer saccharum Marsh. trees on FCO2, comparing FCO2 within 1 m of mature stems to background fluxes before and after an intense rainfall event. Wetting significantly increased background FCO2 (6.4±0.3 vs. 8.6±0.6 s.e. μmol CO2 m-2s-1), with a much larger enhancement near tree stems (6.3±0.3 vs. 10.8±0.4 μmol CO2 m-2s-1). FCO2 varied significantly among individual trees and post-rain values increased with tree diameter (with a slope of 0.058 μmol CO2 m-2s-1 cm-1). Post-wetting amplification of FCO2 (the ‘Birch effect’) in root zones often results from the improved mobility of labile carbohydrates and further metabolization of recalcitrant organic matter, which may both occur at higher densities near larger trees. Our results indicate that plant-soil feedbacks change through tree ontogeny and provide evidence for a novel link between whole-system carbon fluxes and forest structure.

D-type cyclins encode G1/S cell cycle checkpoint proteins, that play a crucial role in defining cell cycle exit and progression. Precise control of cell cycle exit is vital during embryonic development, with defects in the pathways regulating intracellular D-type cyclins resulting in abnormal initiation of stem cell differentiation in a variety of different organ systems. Furthermore, stabilisation of D-type cyclins is observed in a wide range of disorders characterised by cellular over-proliferation, including cancers and overgrowth disorders. In this review, we will summarise and compare the roles played by each D-type cyclin during development and provide examples of how their intracellular dysregulation can be an underlying cause of disease.

We recently demonstrated the effectiveness of long-term treatment with rifaximin and the probiotic VSL#3 at improving urogenital and gastrointestinal symptoms in patients with both chronic inflammatory prostatitis (IIIa prostatitis) and diarrhea-predominant irritable bowel syndrome (IBS-D), relative to patients with IBS-D alone. Because low-grade inflammation of the intestine and prostate may be one of the reasons for co-developing both IIIa prostatitis and IBS-D, we designed the present study to once again evaluate the efficacy of combined rifaximin and VSL#3 treatment in patients affected by IIIa prostatitis plus IBS-D, but we also measured seminal plasma pro-inflammatory (IL-6) and anti-inflammatory (IL-10) cytokines before and after treatment. We consecutively enrolled 124 patients with IIIa prostatitis and IBS-D (diagnosed using the Rome III criteria). Patients were randomized into two groups: group A (n=64) was treated with rifaximin (seven days per month for three months) followed by VSL#3, and group B (n=60) was treated with a placebo. At the beginning of the study and after three months of treatment, all patients completed NIH-CPSI and IBS-SSS questionnaires to score the severity of their urogenital and gastrointestinal symptoms, and we measured seminal plasma levels of IL-6 and IL-10 using ELISA. We defined patients who improved following the treatment as those with a ≥6-point reduction in their NIH-CPSI score or ≥50-point reduction in their IBS-SSS score. By the end of the intervention, 68.7% and 62.5% of patients from group A reported improved NIH-CPSI and IBS-SSS scores, respectively, compared to only 3.3% and 5% of the placebo group. Group A patients also had significantly lower mean seminal plasma levels of IL-6 (11.3 vs 32.4 pg/mL) and significantly higher mean levels of IL-10 (7.9 vs 4.4 pg/mL) relative to baseline, whereas levels of IL-6 and Il-10 did not change in the placebo group. The co-occurrence of two clinical phenotypes (IBS-D plus IIIa prostatitis) result in increased intestinal inflammation and altered immune activation, both of which can be balanced by treatment with rifaximin and VSL#3.

The use of low-cost, Remotely Operated Vehicle (ROV) and underwater photogrammetry techniques for 3D reconstruction of shallow hydrothermal vent sites around Paleochori Bay, Milos Island, Greece. Characterising venting fields through interactive bathymetry models produced from still images taken from camera onboard ROV flown over areas of interest in double raster pattern. First time the shallow venting fields on Milos have been actively surveyed using ROV. Areas were successfully surveyed and the bathymetry was reconstructed using SfM photogrammetry with a ~10 cm scale resolution. A diverse range of benthic habitats were surveyed and the resulting topographic models will act as a baseline, providing further characterisation of the vent systems and any evolving seafloor morphology associated with mineral deposition.

Abstract: NFinFET transistors with fin channel length 90nm and a planar MOSFET transistor with channel length 180nm and 90nm are presented with characteristic curves at various gate biases. A finalized algorithm with kink effects is effectively responsible for addressing the field effect transistors. The algorithm includes the modified conventional current-voltage formula and a nonlinear heat-associated kink solution which is simplified as a Gaussian form. Three parameters in modified model includes kN (related with channel width, channel length, and gate oxide capacitor, and proportional to the mobility of carriers)Vth(Threshold Voltage), and (the inverse of Early Voltage). Those parameters are determined to minimize the discrepancies between the measured data and the fitting values, but leave kinks located at around (VGS－Vth), which are deliberately eliminated by the Gaussian form because of the agitation of thermal kink effects. The whole fitting is made to be as close as the as-measured IDS-VDS. In the mean time, those determined parameters are physically meaningful after the analysis has been done.

Background: Probiotics can provide health benefits to an individual by regulation of the immune system. Many clinical trials have found that probiotics can prevent upper respiratory tracts infections. Aim: To perform a systematic review and meta-analysis of available trials to investigate the effectiveness of probiotics in the prevention of upper respiratory tract infections in individuals of all ages. Conclusion: Probiotics were found to be better in reducing the number of participants who experienced acute URTI, the average duration per episode of acute URTI, use of antibiotics in URTI related cases and absence due to URTI. Side effects were found to be minor, making probiotics a good candidate for clinical use. This shows that probiotics are effective in preventing acute URTIs. However, due to limited studies and small sample size, the results are subjected to bias and should be interpreted with care.

The historic western edge of bison (Bison bison) range and the ecological processes that caused its formation are frequently debated with important implications for bison restoration across North America. We test the hypothesis that a combination of bottom-up habitat suitability and top-down harvest pressure from humans were important processes in forming the western edge of bison distribution. Using 9,384 historical journal observations from 1691 – 1928, we employ MaxEnt ecological niche modelling to identify suitable bison habitat across the Western Cordillera from bottom-up climatic, land cover, and topographic factors. We then use mixed-effect logistic regression to test if bison occurrence in journal records can be in part explained by the abundance of Indigenous humans, wolves, or grizzly bears, in addition to MaxEnt-derived habitat suitability. We find support for our hypothesis because of the limited suitable habitat in the Rocky Mountains that likely prevented westward bison dispersal from core habitat, and there was a negative relationship between bison occurrence and human harvest pressure. On this basis, we propose that intensive human harvest from large populations in the Western Cordillera, subsidized by other wildlife, salmon, and vegetation resources, is an underappreciated socioecological process that needs to be restored alongside bison populations. Co-managing bison with Indigenous people will also mitigate the adverse effects of overabundant bison and maximize the ecological and cultural benefits of bison restoration.

The most recent National Research Council Nutrient Requirements for Sheep and Goats was published in 2007, one of the most consequential nutrient requirement recommendations for sheep and goats in the world. It is pertinent to continue the refinement and discussion of nutrient utilization and requirements for the purposes of enhancing the efficiency of production systems, maximizing resource economy, and minimizing the carbon footprint, among others. Progress has been made in the estimation of energy and protein requirements in sheep and goats, mainly utilizing empirical feeding experimentation, comparative slaughter technique and minimum endogenous loss method. In sheep, newer estimates of energy and protein requirements for maintenance and growth and partial efficiencies had been reported since 2007. There were suggestions that energy and protein requirements could have been affected by breed, wool growth, gender and size; with these reported values being similar or lower than the recommended values in international feeding systems such as NRC, ARC, INRA and AFRC. In goats, energy and protein requirements for growing goats were reported to be either higher or lower than the established recommendations, depending upon meat or dairy breeds. Effect of gender on energy requirement appeared to be related to the stage of growth or degree of maturity. Newer data also suggested that the guidelines of the major feeding systems for the entire growth phase may not be adequate for non-pregnant and non-lactating pubertal females. In multiparous pregnant goats, energy and protein requirements for maintenance did not appear to be affected by days of pregnancy, but efficiencies of metabolizable energy and metabolizable protein utilization for pregnancy were. There were suggestions that that metabolizable protein synthesis in the rumen can be predicted from energy intake using combined equations that encompass both sheep and goats, but more data on goats were called for to account for specific differences in nutrition. In addition to sulfur, there has been progress made on the estimation of maintenance and growth requirements of calcium, phosphorus, potassium and magnesium in goats, with suggestions on the consideration of gender and breed differences. Species, level of Intake, genotype, mature size, age, gender, body composition, use of tissue energy, activity, season, and acclimatization continue to be important considerations for the estimation of nutrient requirements in sheep and goats, with emerging factors such as climate change, heat stress, parasitism and secondary plant compounds. Model equations and partial efficiencies used by NRC to predict energy and protein requirements for maintenance, growth, lactation, and fiber have been highlighted and discussed for the purpose of a more focus discussion and refinement for the future. Potential and limitation of both traditional and emerging methodologies in determining the nutrient requirements in sheep and goats were discussed. To justify the research investment, emerging methodologies such as nutrigenomics will have to be linked more directly to the improvement of production efficiency via more precise prediction of nutrient requirement.

Background/Objectives: Vitamin D’s effect on risk health outcomes is often evaluated using prospective cohort studies. Risk ratios (RRs; e.g., hazard ratios or odds ratios) are determined for incidence for participants with baseline serum 25-hydroxyvitamin D [25(OH)D] concentrations below or above specified values. Serum 25(OH)D concentrations vary over time, thereby diluting the effect of 25(OH)D for long follow-up periods. Inverse relationships between RR and follow-up period have been reported for all-cause mortality rate and cancer incidence rates. Here I evaluate the effect for neurological outcomes. Methods: I analyzed how follow-up period affected results from 10 cohort studies of all-cause dementia, 6 studies of Alzheimer’s disease, and 9 for cognitive impairment with respect to vitamin D deficiency. Results: For all-cause dementia, Alzheimer’s disease, and cognitive impairment, respectively, the linear regression fits are RR = 2.9 – 0.14 × years, r = 0.73, p = 0.02; RR = 2.9 – 0.14 × years, r = 0.69, p = 0.13; and RR = 1.8 – 0.066 × years, r = 0.72, p = 0.03. The regression fit to RR for the shortest follow-up period for each outcome is considered the best estimate of vitamin D deficiency’s effect on risk. Those values are approximately twice that found by averaging all RRs without considering the effect of follow-up period. Conclusions: Vitamin D’s effect on risk of neurological conditions should be determined with relatively short follow-up periods after repeated 25(OH)D measurements as warranted during follow-up.

Background/Objectives: The global burden of metabolic dysfunction-associated steatotic liver disease (MASLD) is increasing at an alarming rate. Cardiovascular disease (CVD) is the leading cause of mortality in MASLD patients, therefore, the therapeutic interventions for MASLD should improve coronary risk factors such as obesity, diabetes and dyslipidemia, in addition to improving liver function. The evidence on effect of sodium-glucose cotransporter 2 inhibitors (SGLT2is) which have beneficial pharmacological properties for MASLD, especially the long-term effects, on the progression of MASLD in Asian population is very limited. Methods: The retrospective longitudinal study was performed by using the medical records at the National Center for Global Health and Medicine, Kohnodai Hospital, Japan. We picked up patients with type 2 diabetes who had taken SGLT2is for at least 3 years or longer between April 1, 2014 and March 31, 2018. We collected the data on metabolic parameters, including blood tests and anthropometric parameters, and compared the data before and after the initiation of SGLT2is treatment. Results: During the observation period, 324 patients had taken SGLT2is for 3 years. The 3-year-SGLT2is treatment significantly reduced body weight, hemoglobin A1c, low-density lipoprotein-cholesterol, triglyceride and non-high-density lipoprotein-cholesterol (HDL-C) and significantly increased HDL-C. Furthermore, this treatment significantly improved liver function and the markers for hepatic steatosis and hepatic fibrosis. Conclusions: Considering that the development of CVD determines the prognosis of MASLD patients, the long-term SGLT2is treatment may be an ideal therapy for MASLD patients.

Study Objectives: The aim of this study is to explore the association between serum 25-hydroxyvitamin D [25(OH)D] levels, a marker of Vitamin D status, and excessive daytime sleepiness (EDS), expressed as increased scores of Epworth Sleepiness Scale (ESS), in a group of prospectively enrolled patients with obstructive sleep apnea (OSA). Methods: Newly diagnosed patients with OSA, divided into two groups, those with EDS (ESS>10) and those without EDS (ESS

It is a well-established fact that inadequate Vitamin D (Vit-D) levels have negative effects on the development and progression of malignant diseases, mainly cancer. The purpose of this paper was to elucidate the effects of Vit-D intake and serum 25-hydroxyvitamin-D (25(OH)D) levels on cancer incidence and mortality, the current evidence in this field, and the biases of this evidence using the meta-meta-analysis method. Meta-analyses focusing on Vit-D intake, serum 25(OH)D levels, and cancer risk/mortality were identified. A structured computer literature search was performed in PubMed/Medline, Web of Science (WoS), and Scopus electronic databases using predetermined keyword combinations. Primary and secondary meta-meta-analyses were carried out, combining odds ratios (ORs), risk ratios (RRs), and hazard ratios (HRs) for outcomes reported in selected meta-analyses. A total of 35 eligible meta-analyses assessing the association between Vit-D and cancer incidence and/or mortality were included in this study. In the pooled analysis, higher Vit-D intake and serum 25(OH)D levels were associated with lower cancer risk (OR = 0.93, 95% CI: 0.90-0.96, p < 0.001; OR = 0.80, 95% CI: 0.72-0.89, p < 0.001, respectively) and cancer-related mortality (RR = 0.89, 95% CI: 0.86-0.93, p < 0.001; RR = 0.67, 95% CI: 0.58-0.78, p < 0.001, respectively). When meta-analyses whose primary reports included only randomized controlled trials were pooled, there was no significant association between Vit-D intake and cancer risk (OR = 0.99, 95% CI: 0.97-1.01, p = 0.320). In subgroup analysis, Vit-D consumption was associated with a significant decrease in colorectal and lung cancer incidence (OR = 0.89, 95% CI: 0.83-0.96, p = 0.002; OR = 0.88, 95% CI: 0.83-0.94, p < 0.001, respectively). Taken together, both Vit-D intake and higher 25(OH)D levels may provide remarkable benefits in terms of cancer incidence and mortality, however, careful evaluation according to cancer types is critically important and recommended.

Relationships of the three bryophyte lineages (liverworts, mosses, and hornworts) to vascular plants is a pivotal question in the study of origin and evolution of land plants. In recent decades, this question has been subject to intense phylogenetic analyses using morphological characters, multigene DNA sequences, and genome structural characters. A tentative consensus reached ten years ago suggested that bryophytes are a paraphyletic group, with liverworts being sister to all other land plants and hornworts being sister to vascular plants. However, several more recent nuclear phylogenomic studies have concluded that bryophytes represent a monophyletic group that is sister to vascular plants. A discussion is presented here on strengths and weaknesses of different types of characters (morphological traits, nucleotide sequences, and genome structural arrangements), and their suitability for resolving deep phylogenetic relationships. Moreover, several criteria for credible phylogenetic reconstruction are proposed. Strong statistical support for reconstructed relationships should be derived from high quality, independent characters selected for suitability to the particular question being addressed. The relationships inferred in a study should be congruent with those from as many other lines of phylogenetic evidence as possible. Any incongruities should be explicable by well-understood biological mechanisms. It is concluded that the relationships of the three bryophyte lineages to vascular plants should currently be viewed as unresolved. This is a difficult phylogenetic problem; the land plants underwent a rapid radiation a long time ago. Yet, further exploration of analytical methods and careful choice of characters should lead to eventual elucidation of diversification patterns among early land plants.

Well differentiated liposarcoma (WD-LPS) is a relatively rare tumour, with less than 50 cases occurring per year in the UK. These tumours are both chemotherapy and radiotherapy resistant and present a significant treatment challenge requiring radical surgery. Little is known of the molecular landscape of these tumours and no current targets for molecular therapy exist. We aimed to carry out a comprehensive molecular characterisation of WD-LPS via whole genome sequencing, RNA-sequencing and methylation array analysis. A recurrent mutation within exon1 of FOXD4L3 was observed (chr9:70,918,189A>T; c.322A>T; p. Lys108Ter). Recurrent mutations were also observed in Wnt signalling, immunity, DNA repair and hypoxia-associated genes. Recurrent amplification of HGMA2 was observed, although this was in fact part of a general amplification of the region around this gene. Recurrent gene fusions in HGMA2, SDHA, TSPAN31 and MDM2 were also observed as well as consistent rearrangements between chromosome 6 and chromosome 12. Our study has demonstrated a recurrent mutation within FOXD4L3, which shows evidence of interaction with the PAX pathway to promote tumorigenesis.

Surfactant proteins A and D (SP-A and SP-D) belong to the collectin subfamily of C-type oligomeric lectins. They are pattern-recognition molecules (PRM), able to recognise pathogen- or dan-ger-associated molecular patterns (PAMP, DAMP) in the presence of Ca2+ cations. That property enables opsonisation or agglutination of non-self or altered/abnormal self-cells, and contributes to their clearance. Like other collectins, SP-A and SP-D are characterised by the presence of four distinct domains: a cysteine-rich domain (at N-terminus), a collagen-like region, an α-helical neck domain and a globular carbohydrate-recognition domain (CRD) (at C-terminus). Pulmonary sur-factant is a lipoprotein complex, preventing alveolar collapse by reducing surface tension at the air-liquid interface. SP-A and SP-D, produced by type II alveolar epithelial cells, and Clara cells, are not only pattern-recognition molecules but also contribute to the surfactant structure and homeo-stasis. Moreover, they are expressed in a variety of extrapulmonary sites where they are involved in local immunity. The term “cancer” includes a variety of diseases: tumours start from uncontrolled growth of abnormal cells in any tissue which may further spread to other sites of the body. Many cancers are incurable, difficult to diagnose and often fatal. This short review summarises anti- and pro-tumourigenic associations of SP-A and SP-D as well as perspectives of their usefulness in cancer diagnosis and therapy.

Three-dimensional (3D) printing technology, also known as additive manufacturing (AM), has emerged as an attractive state-of-the-art tool for precisely fabricating functional materials with complex geometries, championing several advancements in tissue engineering, regenerative medicine, and therapeutics. However, this technology has an untapped potential for biotechnological applications, such as sensor and biosensor development. By exploring these avenues, the scope of 3D printing technology can be expanded and pave the way for groundbreaking innovations in the biotechnology field. Indeed, new printing materials and printers would offer new possibilities for seamlessly incorporating biological functionalities within the growing 3D scaffolds. Herein, we review the extrusion-based 3D printing modalities emphasizing biosensor applications. We highlighted the application of natural, synthetic, and composite biomaterials as 3D-printed soft hydrogels. Emphasis was placed on the approach by which the sensing molecules were introduced during the fabrication process. Finally, the future perspective was provided.

This paper draws on data from a representative city-wide household food security survey of Nairobi conducted in 2017 to examine the importance of food remitting to households in contemporary Nairobi. The next section of the paper provides an overview of urbanization and the rapid growth of Nairobi which has led to growing socio-economic inequality, precarious livelihoods for the majority, and growing food insecurity, as context for the more detailed empirical analysis of food security and food remittances that follows. It is followed by a description of the survey methodology and sections analyzing the differences between migrant and non-migrant households in Nairobi. Attention then turns to the phenomenon of food remitting, showing that over 50% of surveyed households in the city had received food remittances in the previous year. The paper then uses multivariate logistic regression to identify the relationship between Nairobi household characteristics and the probability of receiving food remittances from rural areas. The findings suggest that there are exceptions to the standard migration and poverty-driven explanatory model of the drivers of rural-urban food remitting and that greater attention should be paid to other motivations for maintaining rural-urban connectivity in Africa.

A careful examination of the fundamentals of electromagnetic theory shows that due to the underlying mathematical assumptions required for Stokes' Theorem, global charge conservation cannot be guaranteed in topologically non-trivial spacetimes. However, in order to break the charge conservation mechanism we must also allow the electromagnetic excitation fields D, H to possess a gauge freedom, just as the electromagnetic scalar and vector potentials $\varphi$ and A do. This has implications for the treatment of electromagnetism in spacetimes where black holes both form and then evaporate, as well as extending the possibilities for treating vacuum polarisation. Using this gauge freedom of D, H we also propose an alternative to the accepted notion that a charge passing through a wormhole necessarily leads to an additional (effective) charge on the wormhole's mouth.

This work addresses the problem of automatic head pose estimation and its application in 3D gaze estimation using low quality RGB--D sensors without any subject cooperation or manual intervention. The previous works on 3D head pose estimation using RGB--D sensors require either an offline step for supervised learning or 3D head model construction which may require manual intervention or subject cooperation for complete head model reconstruction. In this paper, we propose a 3D pose estimator based on low quality depth data, which is not limited by any of the aforementioned steps. Instead, the proposed technique relies on modeling the subject's face in 3--D rather than the complete head, which in turn, relaxes all of the constraints with the previous works. The proposed method is robust, highly accurate and fully automatic. Moreover, it does not need any offline step. Unlike some of the previous works, the method only uses depth data for pose estimation. The experimental results on the Biwi head pose database confirm the efficiency of our algorithm in handling large pose variations and partial occlusion. We also evaluate the performance of our algorithm on IDIAP database for 3D head pose and eye gaze estimation.

Questions: Elevation, biodiversity, and forest structure are commonly correlated, but their relationships near the positive extremes of biodiversity and elevation are unclear. We asked 1) How does forest structure vary with elevation in a high biodiversity, high topographic complexity region? 2) Does forest structure predict vascular plant biodiversity? 3) Is plant biodiversity more strongly related to elevation or to forest structure? Location: Great Smoky Mountains National Park, USAMethods: We used terrestrial LiDAR scanning (TLS) to characterize vegetation structure in 12 forest plots. We combined two new canopy structural complexity metrics with traditional TLS-derived forest structural metrics and vascular plant biodiversity data to investigate correlations among forest structure metrics, biodiversity, and elevation. Results: Forest structure varied widely across plots spanning the elevational range of GRSM. Our new measures of canopy density (Depth) and structural complexity (σDepth) were sensitive to structural variations and effectively summarized horizontal and vertical dimensions of structural complexity. Vascular plant biodiversity was negatively correlated with elevation, and more strongly positively correlated with vegetation structure variables. Conclusions: The strong correlations we observed between canopy structural complexity and biodiversity suggest that structural complexity metrics could be used to assay plant biodiversity over large areas in concert with airborne and spaceborne platforms.

Vitamin D has important anti-inflammatory, anti-microbial properties and plays a central role in host immune response. Due to the crucial role of the kidneys in the metabolism of vitamin D, patients with chronic kidney disease (CKD), are prone to vitamin D deficiency. The resultant reduction in the production of calcitriol, the activated form of vitamin D in patients with CKD is responsible for exacerbating the existing renal impairment and periodontal inflammation. Recent evidence suggests a bidirectional, causal relationship between periodontitis and renal functional status. Both conditions have shared pathophysiologic mechanisms including oxidative stress, increases in the systemic inflammatory burden and impaired host response. This review explores the association between vitamin D, CKD and periodontitis. The review summarises the current evidence base for the classical and non-classical vitamin D metabolic pathways, the biological mechanisms linking vitamin D deficiency, CKD and periodontitis, as well as the bidirectional relationship between the two chronic inflammatory conditions. Finally, the paper explores the impact of vitamin D deficiency on CKD, periodontitis, and related co-morbidities.

The Asian clam Corbicula fluminea is a native aquatic species in Eastern Asia and Africa but has become one of the most ecologically and economically harmful invasive species in aquatic ecosystems in Europe, North America, South America. Due to their natural characteristics as a hermaphroditic species with high fecundity and dispersal capacity, Asian clams are extremely difficult to eradicate once they have infiltrated a waterbody. This is an emerging issue for states in the Northeastern United States as Asian clams expand their range farther North due to climate change. There has been extensive research conducted to develop chemical treatments to reactively control invasive mollusc populations and proactively prevent their further spread. However, treatments are mostly targeted toward biofouling bivalves in industrial settings. A comprehensive review of Asian clam chemical treatments used in open water systems was performed to evaluate molluscicides and identify toxicity ranges of emerging treatments that maximize Asian clam mortality and minimize negative impact to water quality and non-target species. The potential chemical applications in Asian clam control and management are summarized in this report to assist resource managers and practitioners on invasive Asian clam management.

In India, the divorce rate is rising year after year. Divorces are thought to have increased by more than a factor of two during the past two decades. India has great cultural diversity, and each of its states has something unique to offer. The divorce rate in India, which differs from state to state, is among the most frequently discussed subjects. More than 30% of marriages end in divorce in big cities like Delhi, Mumbai, Chennai, and Bangalore. Divorce applications have nearly tripled in the past few years in cities like Delhi, Bangalore, Mumbai, Kolkata, and Lucknow. In India, the divorce rate has increased, especially in small cities. Hence, the reasons behind divorce in India were explored in this article. In order to analyze the causes of divorce, the current study aimed to combine the critical components of TOPSIS and COPRAS methodologies in a fuzzy environment. Additionally, it is shown that a comparison study may pinpoint the characteristics that influence divorces the most.

Background and Objectives. To examine trends in the links between induced abortion and subsequent mental health problems for U.S. women approaching completed fertility. Materials and Methods. Panel data on a nationally-representative cohort of 3,842 ever-pregnant women assessed at mean ages of 15, 22, 28 and 37 years from the National Longitudinal Study of Adolescent to Adult Health (Add Health) were examined for pregnancy outcome-related mental health disorders, with extensive adjustment for confounders including sociodemographic dif-ferences, mental health history, and unwanted pregnancies. Outcomes were defined using pub-lished diagnostic criteria or validated index for depression, anxiety disorder, post-traumatic stress disorder (PTSD), and suicide ideation (affective problems); alcohol abuse, drug abuse, opioid abuse, and cannabis abuse (substance abuse problems); and summary counts of affective problems, substance abuse problems and total disorders. Results were adjusted for abortion under-reporting using cross-wave analysis. Results. The relative risk of mental health disorder with exposure to induced abortion followed an inverted “V” pattern as women aged to midlife, increasing from Wave III (age 22; IRR 1.41) to Wave IV (age 28; IRR 1.67), then dropping sharply by Wave V (age 37; IRR 1.20). The population at-tributable fraction of mental health disorder due to abortion dropped from 18.1% at Wave IV to 8.0% at Wave V. Unlike previous Waves, at Wave V mental health risk was more strongly reduced by exposure to childbirth (IRR 0.70, 95% CI .63, .78, p < .001). Reduced relative metrics at Wave V were not due to reduced prevalence of mental health disorders for ever-aborting women, which increased from Wave IV to Wave V by 1.7%, but increased much more, by 20.5%, for never-aborting women. Conclusion. At midlife approaching completed fertility, differential negative psychological out-comes for ever-aborting U.S. women remained elevated but reduced from younger ages.

Contrasting results have suggested that the prevalence and intensity of post abortion emotional distress (PAD) either diminishes rapidly or persists over time. Few studies have followed women for longer than five years. This study examines retrospective population data on 226 ever aborting U.S. women aged 41-45, at an average of 20 years following the abortion, with extensive measures of PAD. Most post abortive women (55.2%) experienced little or no distress from their abortion(s) and 74.6% were confident it had been the right decision, but 44.8% reported moderate (20.7%) to high (24.1%) distress related to their abortion(s), including 37.7% who reported negative emotions; 31.2% “frequent feelings of loss, grief or sadness;” 24.6% “frequent thoughts, dreams, or flashbacks;” 23.2% for whom thoughts and feelings about their abortion “negatively interfered with life, work, or relationships.” Time since the abortion (mean 20 years, range 0-31 years) was not correlated with PAD (r = -.02, p .71). For the minority of women who experienced it, PAD did not diminish but persisted for decades. An estimated 7.5 million U.S. women currently experience persistent high PAD. Further research to specify risk factors and possible interventions for postabortion distress would be of value for this group of women.

While traditionally people relinquish their pets to an animal shelter or pound, the internet provides a newer method to re-home. We analysed advertisements (ads) on the largest website in Australia for trading dogs and cats, gumtree.com.au. Data was collected in 2016. Dogs were sampled on February 7, 16 and 24, 2016 and cats on February 9, 19 and 26, 2016 with 2640 ads for relinquished dogs, and 2093 ads for relinquished cats. It was estimated >31,000 puppies/dogs and >24,000 kittens/cats are relinquished on gumtree.com.au per year. The median age of dogs was 1.42 and cats 0.9 years of age. There were 23% of dog ads and 62% of cat ads for free animals. Compared to the human population there were proportionately more ads in Queensland and fewer ads in Victoria. A total of 15 people were surveyed who had relinquished a dog or cat using gumtree.com.au. The dog owners used gumtree.com.au because they believed the shelters were full (n = 4), and; they wanted to see/interview the new owner (n = 2). For cat owners it was because they had originally got the cat on gumtree.com.au (n = 2); they use gumtree.com.au for other things, and it works (n = 2), and; they wanted to see/interview the new owner (n = 2). The data collected will be valuable for implementation of policy and interventions to protect the welfare of un-wanted dogs and cats.

Potential of co-digestion mixing thickened secondary sludge (TS) from extended aeration wastewater treatment plant and locally available substrates (whey, grease and septage) has been studied using three steps. The first step was a batch test to determine biological methane potential (BMP) of different mixtures of the three co-substrates with TS. The second step has been carried out with lab-scale reactors (20 L) simulating anaerobic continuous stirred tank reactors fed by three mixtures of co-substrates determined according to previous step results. Modelling using ADM1 as a mechanistic model was applied in the third step to help understanding the co-digestion process. According to BMP step, septage used as co-substrate has a negative effect on performance and addition of 10 to 30% grease or 10% whey would lead to a higher production of biogas and with an increase of the methane content. The results from the reactor showed less evi-dence of the positive effects observed with the BMP assay. Protein and lipid fractions of particu-late biodegradable COD are important variables for digester stability and methane production as predicted by modelling. Results of simulations with ADM1 model adapted to co-digestion confirmed that this model is a powerful tool to optimize the process of biogas production.

The occurrence of ovarian dysfunction is often due to the imbalance between the formation of reactive oxygen species (ROS) and the (in)effectiveness of the antioxidative defense mechanisms. Primary sources of ROS are the respiratory electron transfer and the activity of NADPH oxidases (NOX), while Superoxide dismutases (SOD) are the main key reg-ulators that control the levels of ROS and reactive nitrogen species intra- and extracel-lularly. Because of their central role, SODs are the subject of research on human ovarian dysfunction, but the sample acquisition is low. The high degree of cellular and molecular similarity between Drosophila melanogaster ovaries and human ovaries provides this model organism with the best conditions for analyzing the role of ROS during ovarian function. In this study, we clarify the localization of the ROS producing enzyme dNox within ovaries of Drosophila melanogaster and by a tissue specific knockdown, we show that dNox derived ROS are involved in the chorion hardening process. Furthermore, we analyze the dSod3 localization and show that reduced activity of dSod3 impacts egg laying behavior, but not the chorion hardening process.

Many corporations have now revised their value statements to showcase their commitment to sustainable development and green business due to the pressing issues of climate and environmental damage. Despite the importance of value statements that can direct companies to achieve sustainable goals, what kind of values can be perceived as organizational orientations to sustainability remains unknown. This study explores how the general public views the inclusion of sustainable components in value statements from the listed companies in Hong Kong by using Q-sort methodology (n = 30). Analyzing the final sample of 40 value statements extracted from 27 listed companies, we identified three factors related to sustainability, namely, Empowering business process management, Empowering customer-centric excellence, and Empowering sustainable progress. This study provides an additional component to the traditional triple bottom line by suggesting that internal operation of a company is an emerging idea to understand corporate sustainability.

Disease transmission in wildlife is linked to ecosystem and human health, and host community structure can mediate pathogen spread. Here, we decompose the well-known susceptible-infected (SI) compartmental models of disease transmission for multi-host communities to explore the disease-biodiversity relationship. We examine the parameters involved in interspecific transmission and link them to the multi-host outbreak potential, R0. We partition R0 into its separate elements that can be associated with either the recipient or donating host, and show how this allows us to identify maintenance versus spillover hosts, allowing us to quantify separate stages of spillover into a novel, recipient host. We further suggest that the evolutionary relatedness between donating and recipient host may play a role in the probability a pathogen establishes in a novel species, as illustrated by the observed phylogenetic signal in the host-breadth of multi-host pathogens. We discuss how anthropogenic changes to the environment and wildlife communities, such as the reduction and fragmentation of wildlife habitat, might alter the mode and dynamics of disease transmission. This discussion contributes to the ongoing debate on the relationship between disease incidence and biodiversity. Through a synthesis of classic ecological theory, we illustrate how pathogens can affect host populations through phenomena such as in/direct symbioses, that can save a pathogen from extinction or suppress competing host species, but we highlight how host diversity can simultaneosuly influence the survival and success of the pathogen, suggesting a complex feedback between hosts and parasites in multi-host communities. Our review provides a guide to common derivations of interspecific transmission, and underscores the critical connections between community and disease-ecology.

Background Obesity is a major healthcare challenge worldwide. Recently, glucagon-like peptide-1 receptor agonists (GLP-1RAs) have emerged as a promising pharmacological option for managing type 2 diabetes mellitus (T2DM) and obesity in diabetic patients. Objective This systematic review aims to evaluate the efficacy and safety of GLP-1RAs in nondiabetic patients. Methods We systematically reviewed 2356 published articles from the past ten years (2013 to November 22, 2023). After rigorous screening, 11 articles were selected for an in-depth review. The analysis focused on the efficacy and safety of GLP-1RAs in nondiabetic patients, considering various baseline characteristics and subgroups. Results The review found that GLP-1RAs, including exenatide, liraglutide, semaglutide, and the dual glucose-dependent insulinotropic polypeptide and glucagon-like peptide-1 receptor agonist (GIP/GLP-1RA) tirzepatide, significantly promoted weight loss in obese/overweight nondiabetic patients. Additionally, these agents positively affected cardiovascular risk factors such as blood pressure, glycemic control, nephropathy, lipid levels, serum insulin levels, and C-reactive protein (CRP) profiles. However, GLP-1RAs, including tirzepatide, were associated with gastrointestinal adverse drug reactions such as nausea, diarrhea, vomiting, and constipation. These adverse events were typically transient, mild-to-moderate in severity, and subsided over time. Conclusion GLP-1RAs are effective and relatively safe for weight management and improving cardiovascular risk factors in nondiabetic patients, despite the occurrence of some gastrointestinal side effects. Further research is warranted to optimize the use of these agents in nondiabetic populations.

We previously reported how the loss of CHIP expression (Carboxyl terminus of Hsc70-Interacting Protein) during pressure overload resulted in robust cardiac dysfunction, accompanied by a failure to maintain ATP levels in the face of increased energy demand. In this study, we analyzed the cardiac metabolome after seven days of pressure overload and found an increase in long- and medium-chain fatty acid metabolites in wild-type hearts, a response that was attenuated in mice that lack expression of CHIP (CHIP^-/-). These findings suggest that CHIP may play an essential role in regulating oxidative metabolism, pathways that are regulated in part by the nuclear receptor PPARα (Peroxisome Proliferator-Activated Receptor alpha). Next, we challenged CHIP^-/- mice with the PPARα agonist, fenofibrate. Surprisingly, treating CHIP^-/- mice with fenofibrate for five weeks under non-pressure overload conditions resulted in a loss of skeletal muscle mass and a marked increase in cardiac fibrosis, accompanied by a decrease in cardiac function. Isolated CHIP^-/- cardiac fibroblasts treated with fenofibrate did not increase synthesis of collagen or TGFβ, suggesting that the fibrosis observed in CHIP^-/- hearts likely depends on signaling from other cell types or circulating factors. In conclusion, in the absence of functional CHIP expression, fenofibrate results in unexpected cardiac pathologies. These findings are particularly relevant to patients harboring loss-of-function mutations in CHIP and are consistent with a prominent role for CHIP in regulating cardiac metabolism.

Background: given the various clinical manifestations that characterize coronavirus disease 2019 (COVID-19), the scientific community is constantly searching for biomarkers with prognostic value. Surfactant protein A (SP-A) and D (SP-D) play a crucial role in ensuring proper alveolar function and an alteration of their serum levels have been reported in several pulmonary diseases characterized by acute respiratory distress syndrome (ARDS) and pulmonary fibrosis. Consid-ering that such clinical manifestations can also occur during severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, we wondered if these collectins could act as prognostic markers. Methods: in this regard, serum levels of SP-A and SP-D were measured by enzyme immunoassay in patients with SARS-CoV-2 infection (n=51) at admission (T0) and after 7 days (T1) and compared with healthy donors (n=11). Results: SP-D increased in COVID-19 patients com-pared to healthy controls during the early phases of infection, while a significant reduction was observed at T1. Stratifying SARS-CoV-2 patients according to disease severity, increased serum SP-D levels were observed in severe compared to mild patients. Conclusions: In the light of these results SP-D, but not SP-A, seems to be an eligible marker of COVID-19 pneumonia and the early detection of SP-D serum levels could be crucial for a preventive clinical management.

In atomic GdFe$_2$ films capped by 4$d$ and 5$d$ transition metals, we show that skyrmions with diameters smaller than 12 nm can emerge. The Dzyaloshinskii--Moriya interaction (DMI), exchange energy, and the magnetocrystalline anisotropy (MCA) energy were investigated based on density functional theory. Since DMI and MCA are caused by spin--orbit coupling (SOC), they are increased with 5$d$ capping layers which exhibit strong SOC strength. We discover a skyrmion phase by using atomistic spin dynamic simulations at small magnetic fields of $\sim$1 T. In addition, a ground state that a spin spiral phase is remained even at zero magnetic field for both films with 4$d$ and 5$d$ capping layers.

Diet plays a pivotal role in the overall health of an individual. Not only does it help carry out and regulate certain physiological functions, but it also can determine the composition of the gut microbiome. While the relative number of microorganisms that make up the gut microbiome vary between individuals and can be dependent on different environmental factors, there is evidence to suggest that composition of the microbiome can correlate with overall health or disease. When the GI microbiome is disturbed or suddenly changes it results in microbiome dysbiosis, a condition that correlates with the presence of certain diseases. Diseases linked to microbiome dysbiosis range from metabolic disorders, inflammatory bowel diseases to disorders of the brain. Many of these diseases are linked to the connection between the brain and the gut, known as the brain-gut axis. This bidirectional communication is important to maintain normal intestinal function, but is also responsible for the GI response to emotions as well as the emotional response to GI disturbances. By exploiting the interaction between microbiome health and nutrition, diet can be used to alleviate disease symptoms, protect against the development of certain conditions, and better maintain overall health. This review will examine the effects of nutrition on the microbiome, diseases linked to disruption of the normal microbiome, and the way that altering the diet can mitigate symptoms or prevent disease.

Background: Vasoactive Intestinal Peptide (VIP) is known to bind to and protect the Alveolar Type II cell by blocking replication of the SARS-CoV-2 virus, upregulating surfactant production, blocking apoptosis, and blocking cytokine effects. RLF-100 (Aviptadil), a synthetic form of Vasoactive Intestinal Peptide (VIP) has been granted Fast Track Designation and is currently in phase 2/3 placebo-controlled trials. FDA has granted Emergency Use IND and Expanded Access Protocol approval for the use of RLF-100 in patients whose comorbidities render them ineligible for inclusion in the ongoing pivotal trial. Methods: This report describes the first 6 patients with Acute Respiratory Failure in Critical COVID-19, enrolled under Emergency Use IND were treated with three successive 12-hour infusions of intravenous Aviptadil at 50/100/150 pmol/kg/hr, while continuing to receive maximal ICU care. Results: Median patient follow-up time is 14 days. So far, all treated patients have survived. Improved radiographic appearance of typical “ground glass” COVID-19 features to varying degrees is seen in all patients within 72 hours. Improvement in blood oxygenation is seen in all patients, with complete remission from respiratory failure in 4 of 6 patients. An average 56% reduction in inflammatory markers was seen, together with a median 4 point reduction in the NIAID Ordinal Scale. 2/6 patients were discharged from the hospital and 1 patient was downgraded to the general medicine floor. Comment: The short term survival of 6/6 patients with respiratory failure in the setting of COVID-19 and major comorbidity is the most dramatic response ever seen with an antiviral agent. Improvement in radiographic appearance, oxygenation requirement, and inflammatory markers is consistent with in vitro evidence of direct anti-viral effect.

As predicted by the theory of super dielectric materials, simple tests demonstrate that dielectric material on the outside of a parallel plate capacitor dramatically increases capacitance, energy density, and power density. Simple parallel plate capacitors with only ambient air between the plates behaved as per standard theory. Once the same capacitor was partially submerged in deionized water [DI], or DI with low dissolved NaCl concentrations, still with only ambient air between the electrodes, the capacitance, energy density, and power density, at low frequency, increased by more than seven orders of magnitude. Notably, conventional theory precludes the possibility that material outside the volume between the plates will in any fashion impact capacitive behavior.

This paper seeks to model the crack propagation in of AAs (aluminum-alloys) 2524-T3 and 7050-T7452 subjected to fatigue loading at low temperature. Fatigue crack growth tests were performed on AAs 2524-T3 and 7050-T7452 subjected to constant-amplitude and actual random-spectra loading histories at room temperature of about 25 °C and at cryogenic temperature of -70 °C, respectively, to determine their crack growth properties and residual lives. The interaction mechanisms between cryogenic temperature and the fatigue load were deduced on the basis of the results of fractographic analysis. Temperature-dependent residual lives under actual random-spectrum load history were modeled based on a modified accumulation damage rule by accounting for the load interaction. Good correlation was achieved between the predictions and actual experiments, demonstrating the practical and effective use of the proposed method.

The purpose of this review is to elucidate the actual threat of the most prevalent mycotoxins in agricultural commodities and human/animal food/feed for appearance of foodborne ailments and diseases. The underestimated hazard of joint mycotoxin uptake of animals or humans is critically discussed with regards to synergistic or additive interaction between some target mycotoxins. The real toxicity of target mycotoxin combinations as it happens in practice is evaluated and possible lower limit values or control measures are suggested in such cases. Some critical points in adequate risk assessment, hygiene control and regulation of mycotoxns are discussed. The efficiency of current mycotoxin regulations and control measures is evaluated in regards to human/animal health hazard. The risk assessment in the case of multiple mycotoxin exposure of humans/animals via the food/feed or agricultural commodities is evaluated and some suggestions are proposed in such cases. Appropriate control measures and food safety issues throughout the food supply chain are proposed in order to prevent target foodborne diseases. Some preventive measures and possible veterinary hygiene control or risk assessment are proposed in some practical cases of foodborne diseases for preventing mycotoxin contamination of animal products designed for human consumption and to avoid possible public health issues.

Dirac's Large Number Hypothesis (LNH), proposed in 1937, has captivated the scientific community with its exploration of profound correlations between cosmic and atomic scales. This hypothesis delves into the intricate interplay between the infinitesimally small and the vastly large, offering potential insights into the fundamental nature of the universe. As we continue to uncover the mysteries of the cosmos, the LNH oscillates on the precipice of scientific acceptance—neither fully validated nor entirely dismissed. In this review paper, we embark on a comprehensive journey through Dirac's LNH, shedding light on its theoretical underpinnings, its implications for universe models, and its resonance with the Anthropic Principle. We delve into the possibilities of variable gravitational constants and continuous mass creation, inviting further exploration into the intricacies of our cosmic symphony. By embracing the ongoing quest for understanding, we endeavor to unravel the profound harmonies that connect the infinitesimal with the infinite, contributing to the symphony of knowledge in theoretical physics and cosmology.

Cyberattacks are rapidly evolving both in terms of techniques and frequency, from low-level attacks through to sophisticated Advanced Persistent Threat (APT). There is a need to consider how testbed environments such as cyber ranges can be readily deployed to improve examination of attack characteristics and the assessment of defences. Whilst cyber ranges are not new, they can often be computational expensive, require significant setup and configuration, or may not provide full support for areas such as logging or ongoing learning. In this paper, we propose GoibhniUWE, a container-based cyber range that provides a flexible platform for investigating the full lifecycle of a cyber attack. Adopting a modular approach, users can seamlessly switch out existing, containerised vulnerable services, deploying multiple different services at once allowing for the creation of complex and realistic deployments. The range is fully instrumented with logging capabilities from a variety of sources including Intrusion Detection Systems (IDS), service logging, and network traffic captures. To demonstrate the effectiveness of our approach, we deploy the GoibhniUWE range under multiple conditions to simulate various vulnerable environments, reporting on and comparing key metrics such as CPU and memory usage. We simulate complex attacks which span multiple services and networks, with logging at multiple levels, modelling an Advance Persistent Threat (APT) and their associated Tactics, Techniques, and Procedures (TTPs). We find that even under continuous, active and targeted deployment GoibhniUWE averaged a CPU usage of less than 2 processors and memory usage of less than 4.5 GB.

It is unclear whether military shoes (combat boots and sports shoes) attenuate loading rate or affect force transfer during walking. Therefore, this study compared ground reaction forces (GRF) related to impact and force transfer between combat boots, military sports shoes and running shoes. Ten army recruits walked over a walkway with two force plates embedded. GRF were measured when walking barefoot (for data normalization) and with combat boots, military sports shoes and running shoes. Loading rate, first and second peak forces and push-off rate of force were computed along with temporal analysis of waveforms. Reduced loading rate was observed for the running shoe compared to the combat boot (p = 0.02 and d = 0.98) and to the military sports shoe (p = 0.04 and d = 0.92). The running shoe elicited a smaller second peak force than the combat boot (p < 0.01 and d = 0.83). Walking with military shoes and combat boots led to larger force transfer then running shoes potentially due to harder material used in midsole composition (i.e. styrene-butadiene rubber). These results could lead to a potentially larger risk of injuries while long duration walking in military shoes and boots compared to traditional running shoes.

Large power transformers are generally associated with a maximum capacity rating of 100 MVA or higher. These large liquid dielectric power transformers are a custom-built piece of equipment, thus very expensive, and a backbone element of the power grid. In extreme cases as, for example, severe geomagnetic disturbances, permanently monitoring their condition will enhance their electrical reliability and resilience to guarantee efficient management of its life cycle. However, some traditional monitoring/diagnosis techniques have singular features when applied to large power transformers and their interlinked subsystems. In this context, and since that information is hardly put in evidence and compiled in the literature, this paper reviews the particularities of monitoring and diagnosing those assets.