Globally, rotavirus group A (RVA) remains a major cause of severe childhood diarrhea, despite the use of vaccines in > 100 countries. RVA sequencing for local outbreaks facilitates investigation into strain composition, origins, spread, and vaccine failure. In 2018, we collected 248 stool samples from children aged <13 years admitted with diarrheal illness to Kilifi County Hospital, coastal Kenya. Antigen screening detected RVA in 55 samples (22.2%). Of these, VP7 (G) and VP4 (P) segments were successfully sequenced in 48 (87.3%) and phylogenetic analysis based on the VP7 sequences identified seven genetic clusters with six different GP combinations; G3P[8], G1P[8], G2P[4], G2P[8], G9P[8] and G12P[8]. The G3P[8] strains predominated the season (n=37, 67.2%) and comprised three G3 genetic clusters that fell within Lineage I and IX (the latter also known as equine-like G3 lineage). Both two G3 lineages have been recently detected in several countries. Our study is the first to document African children infection with G3 lineage IX. These data highlight the global nature of RVA transmission and the importance of increasing global rotavirus vaccine coverage.

A New monogalactosyldiacylglycerol (MGDG), a known monogalactosylmonoacylglycerol (MGMG) and a known polyunsaturated fatty acid methyl ester (PUFAME) were isolated from the marine dinoflagellate Karenia mikimotoi. The planar structure of the glycolipids was elucidated using MS and NMR spectroscopic analyses and comparisons to the known glycolipid to confirm its structure. The isolation of PUFAME strongly supports the polyunsaturated fatty acid fragment of these glycolipids. The relative configuration of the sugar was deduced by comparisons of 3JHH values and proton chemical shifts with those of known glycolipids. All isolated compounds MGDG, MGMG and PUFAME (1-3) were evaluated for their antimicrobial and anti-inflammatory activity. All compounds modulated macrophage responses, with compound 3 exhibiting the greatest anti-inflammatory activity.

The temperature of the indoor environment is important for health and wellbeing especially at the extremes of age. The study aim was to undertsand the relationship between self-reported thermal sensation and extremity skin temperature in care home residents with and without dementia. The Abbreviated Mental Test (AMT) was used to discriminate residents to two categories, those with and those without dementia. After acclimatisation, measurements included: tympanic membrane temperature, thermal sensation rating followed by infrared thermal mapping of non-dominant hand and forearm. Sixty-nine afebrile adults (60-101 years of age) were studied in groups of two to five, in mean ambient temperatures of 21.4^oC-26.6^oC (median 23.6^oC). Significant differences were observed between groups; thermal sensation rating (p=0.02), tympanic temperature (p=0.01), fingertip skin temperature (p=0.01) and temperature gradients; fingertip-wrist p=0.001 and fingertip-distal forearm, p=0.001.

A Brewer Spent Grain (BSG), the most abundant by-product of the brewing process, is mainly used in animal feed and biogas production. The aim of the present work is BSG valorization by yeast fermentation to produce carotenoids. R. mucilaginosa CBS316 was cultured on BSG syrups, supplemented or not with YE and PEP (s-Fsa and Fsa). The biomass and carotenoid production were optimized in flasks and then scaled-up in bioreactor. In flask tests, the maximum biomass concentration was 5.3 and 6.2 g/L for Fsa and s-Fsa cultures, respectively. The maximum carotenoid production was 833 μg/L in Fsa and 1159 μg/L in s-FSA. Considering that the highest specific productivity value (P 7.16 μg/g*h) was obtained with Fsa syrup, this medium was selected for the process scale-up. In bioreactor tests, the maximum concentrations of biomass (4.29 g/L) and carotenoid (396 ug/L) was reached at 72 hours of fer-mentation, 24 h later than in flask. The total carotenoid produced was 524 and 150 ug in bioreactor and flask cultures, respectively. The carotenoids production by R. mucilaginosa was obtained both in Fsa and s-Fsa syrups. The results confirm the possibility to use the syrup as it is, Fsa, thus limiting the process costs.

In this paper, we have established Hermite-Hadamard inequalities for r-preinvex functions via fractional integrals.

This paper presents a new engagement model for climate change education (CCE) as a result of analysing interactive digital narratives (IDNs) created during the You and CO2 Climate Change Education Programme. Young people aged 13-15 from two schools in Wales participated in three workshops, which culminated in students producing IDNs about climate change using Twine storytelling software. An inductive, grounded-theory approach informed by Bourdieusien principles of habitus and value was used to explore students’ responses to the Programme. Stage 1 coding identified ‘Core Themes’ and located student responses along tri-axial continua showing engagement, agency, and power. Stage 2 coding combined ‘Core Themes’ to build upon Cantell’s 2019 Bicycle Model of Climate Change Education to create a new ‘Holistic Engagement Model for Climate Change Education and Action’ (HEMCCEA), where learners’ journeys towards full engagement with and understanding of CCE and action could be traced. Barriers to students’ engagement with and understanding of CCE were identified through Bourdieusien analysis of responses. Results show that engagement was related to children’s views on their capacity to effect change on individual, local and governmental level. The HEMCCEA provides a model for adjusting CCE curricula to accommodate young people’s varying cultures and views.

Preterm delivery can be precipitated by infection, and preterm infants are at heightened risk of postnatal infection. Little is known about the ontogeny of inflammatory biomarkers in extremely preterm infants. We hypothesized that suspected prenatal infection (chorioamnionitis or spontaneous preterm labor) and clinically diagnosed postnatal infection would be associated with unique biomarker signatures, and those patterns would be influenced by the degree of prematurity. Venous blood was collected daily for the first week and weekly for up to 14 additional weeks from 142 neonates born at 22-32 weeks gestation. A custom array was utilized to measure monocyte chemoattractant protein-1 (MCP-1) and interleukin-6 (IL-6). C-reactive protein (CRP) levels were obtained from the electronic medical record. 90 infants had suspected prenatal infection and 63 were diagnosed with postnatal infection. Independent of gestational age at delivery, MCP-1 was significantly increased (P < 0.001) in association with maternal preeclampsia, but MCP-1 was decreased (P<0.01) and CRP was increased (P<0.05) in the presence of chorioamnionitis. IL-6 and CRP were both increased in infants diagnosed with postnatal infection with peak levels observed on days 2 and 3, respectively. In conclusion, suspected prenatal and postnatal infections and non-infectious complications of pregnancy are associated with unique biomarker profiles, independent of gestational age. In those clinically diagnosed with a postnatal infection in the absence of antenatal infection concerns, IL-6 increases before CRP, emphasizing a potential role for expanded biomarker screening if antibiotics are initially avoided in infants born exclusively for maternal indications.

The hyperactivation of the sympathetic nervous system (SNS) is linked to obesity, hypertension, and type 2 diabetes, with elevated norepinephrine (NE) levels being a key feature. Previous research has shown increased sodium-glucose cotransporter 1 (SGLT1) protein in kidneys of hypertensive rodents, prompting investigation into SGLT1 expression in other tissues such as skeletal muscle. This study aimed to assess: i) whether skeletal muscle cells and tissue express SGLT1 and SGLT2 protein; ii) if NE increases SGLT1 in skeletal muscle cells and iii) whether skeletal muscle of neurogenically hypertensive mice exhibits increased SGLT1 expression. We found that i) skeletal muscle cells and tissue are a novel source of SGLT2 protein and ii) NE significantly elevated SGLT1 in skeletal muscle cells. As SGLT2 inhibition (SGLT2i) with Empagliflozin increased SGLT1, in vivo studies with the dual SGLT1/2i, Sotagliflozin were warranted. Treatment of neurogenically hypertensive mice with Sotagliflozin significantly reduced blood pressure. Our findings suggest that SNS activity upregulates the therapeutic target, SGLT1 in skeletal muscle, potentially worsening cardiometabolic control. As clinical trial data suggests cardiorenal benefits with SGLT2i, future studies should aim to utilize sole SGLT1i which may offer a therapeutic strategy for conditions with heightened SNS activity, such as hypertension, diabetes and obesity.

In 2016–2017, we conducted and published a systematic review on caffeine safety [1] that set out to determine whether conclusions presented in the heavily cited Health Canada assessment, Nawrot et al. [2], remain supported by more recent data. To that end, we reviewed data from 380 studies published between June 2001 and June 2015, which were identified from an initial batch of over 5,000 articles through a stringent search and evaluation process [1]. In the current paper, we use plain language to summarize our process and findings, with the intent of sharing additional context for broader reach to the general public. We addressed whether caffeine doses previously determined not to be associated with adverse effects by Health Canada (400 mg/day for healthy adults, 300 mg/day for pregnant women, 2. 5 mg/kg body weight/day for adolescents and children, and 10 g/day for acute effects) remain appropriate for five outcome areas (acute toxicity, cardiovascular toxicity, bone & calcium effects, behavior, and development and reproduction) in healthy adults, pregnant women, adolescents, and children. We used a weight-of-evidence approach to draw conclusions for each of the five outcomes, as well as more specific endpoints within those outcomes, which considered study quality, consistency, level of adversity, and magnitude of response. In general, updated evidence confirms the levels of intake put forth by Nawrot et al., as not being associated with any adverse health effects, and our results support a shift in caffeine research from healthy to sensitive populations.

Background: Exposure to environmental tobacco smoke (ETS) presents substantial health risks for pregnant women and newborn infants. Measurements of ETS include invasive and expensive biochemical tests as well as less invasive and lower-cost self-reported exposure and avoidance measures. Better understanding of self-report measures will help to select ETS assessments for evaluation. Methods: This analysis was conducted within the context of a tailored video intervention to reduce tobacco smoking and ETS exposure during pregnancy and after delivery, in the control group sample of 147 nonsmoking women. Measurements of salivary cotinine concentration, self-reported ETS exposure and avoidance behaviors were captured at 32 weeks gestation and 6 months postpartum. Results: Salivary cotinine concentration was significantly related to ETS avoidance among pregnant nonsmokers at 32 weeks gestation, but not ETS exposure. At 6 months postpartum, both the reported ETS exposure of the infant and maternal avoidance behaviors to reduce her infant’s exposure were associated with the infant’s salivary cotinine concentration. At 32 weeks gestation and 6 months postpartum, avoidance behaviors decreased as exposure increased. Discussion: This study suggests that for nonsmoking women during pregnancy, report of tobacco smoke avoidance is more valid than report of exposure. After delivery, self-reported ETS exposure or avoidance are associated with each other and biochemical measurement of salivary cotinine. These results provide researchers and clinicians with evidence to support inclusion of avoidance behaviors in the selection of ETS measure.

Gout is at least 3 times more prevalent in men than in women. However, concurrent with rising total gout prevalence, complex factors, including comorbidities, diet and lifestyle, and aging, have promoted higher gout prevalence in females. This narrative review focuses on summarizing recent developments in the landscape of gout in women, and mechanisms involved. New knowledge on sex hormone effects on both urate-excreting and urate-reabsorbing transporters, and higher hypertension and chronic kidney disease prevalence in women compared to men, may help explain why gout incidence rises robustly after menopause in women to approach that in men. Racial and ethnic factors, risk profiles based on heritable genetic polymorphisms of urate transporters, and diet, body mass index, and lifestyle factors differ according to sex. In addition, sex differences in clinical phenotypes and outcomes of gout and non-gout illnesses include more frequent comorbidities, more pain and disability during gout flare, different perceptions of disease burden, and more frequent severe cutaneous hypersensitivity reaction to allopurinol in women. Significantly, women with gout also have poorer COVID-19 outcomes than do men. Collectively, such findings support the potential clinical benefits of tailoring gout and hyperuricemia treatment according to sex.

In this paper, we classify the function space of all real-valued functions on R denoted as F(R,R) into 28 distinct blocks. Each block contains elements that share common features in terms of the cardinality of their sets of continuity and differentiability. Alongside this classification, we introduce the concept of the Connection, which reveals a special relationship structure between four well-known real-valued functions in real analysis: the Cantor function, Dirichlet function, the Thomae function, and the Weierstrass function. Despite the significance of this field, several perspectives remain unexplored.

The effective Supervisory Control and Data Acquisition (SCADA) system can improve the reliability, safety and economic benefits of microgrid operation. In this research, the lower central controller and upper WEB monitoring system are connected by the SCADA system which is as the hub of microgrid intelligent monitoring platform. This system contains a set of specific functions programmed by Java as a middleware which can provide control and communication between the central controller and the upper monitoring system. The system realizes the real-time data acquisition and storage, the control instructions parsing and transmitting, the microgrid security and stability, the load balancing and resource recovery of the microgrid. All that functions have been tested and verified in the actual operation.

Cyclic STAT3 decoy (CS3D) is a second-generation, double-stranded oligodeoxynucleotide (ODN) that mimics a genomic response element for signal transducer and activator of transcription 3 (STAT3), an oncogenic transcription factor. CS3D competitively inhibits STAT3 binding to target gene promoters, resulting in decreased expression of proteins that promote cellular proliferation and survival. Previous studies have demonstrated antitumor activity of CS3D in preclinical models of solid tumors. However, prior to entering human clinical trials, the efficiency of generating the CS3D molecule and its stability in biological fluids should be determined. CS3D is synthesized as a single-stranded ODN and must have its free ends ligated to generate the final cyclic form. In this study, we report a ligation efficiency of nearly 95 percent. The ligated CS3D demonstrated a half-life of 7.9 hours in human serum, indicating adequate stability for intravenous delivery. These results provide requisite biochemical characterization of CS3D that will inform upcoming clinical trials.

Introduction: It may be feasible to detect episodic memory change in preclinical Alzheimer’s disease (AD) to indicate navigational risks and AD prior to mild cognitive impairment. The establishment of episodic memory signatures may allow for biomarker mapping to inform diagnostic research and practiceMethods: Retrospective longitudinal mixed methods and cross-sectional effect size, to compare group differences, are applied to the Craft-21 memory scores from the preclinical years of persons who later developed AD (pre-AD) dementia , n = 175 with 112 females and 63 males. Their scores are compared to cognitively normal controls (non-AD) n = 6,814 with 4,232 females and 2,582 males. Pre-AD and non-AD groups are further analyzed by biological sex. The dataset is from the National Alzheimer’s Coordinating Center funded by NIA/NIH Grant U24 AG072122. Results: The pre-AD episodic memory scores decreased an average of -.510, p < .001 versus (vs.) the non-AD annual increase by .127, p < .001. The first Cohen’s d = .482 and last Cohen’s d = 976, p < .001. The pre-AD females had an average annual decreased of -.762, p < .001 vs. non-AD females increase of .117, p < .001. The first Cohen’s d = .576 and last Cohen’s d = 1.133, p <.001. The pre-AD males increased every year by .185, p = .996 vs. the non-AD males annual increase of .185, p < .001. The first Cohen’s d = 1.054 decreased by the last year to Cohen’s d = .680, p <.001Discussion: Distinct decline in episodic memory occurs for pre-AD females, but there is not a significant change in pre-AD males. However, the effect size difference between both pre-AD and non-AD groups suggests biomarker mapping in conjunction with memory trajectories may be feasible to determine potential navigational risks as well as biological and cognitive preclinical AD.

Ethical behaviour tends to lead to welfare consideration of animals, but much less so for invertebrates. Indigenous tradition often valued all animals having an important role in the life on the planet, a practical application of modern ecology. The Judaeo-Christian-Islamic tradition postulated ‘man’ as having dominion over all the earth, resulting in anthropocentrism and careless practices. In contrast, the Buddhist/Hindu beliefs in rebirth leads to ahisma or doing no harm. In the face of capitalist systems, practice does not necessarily follow these beliefs, especially in the ‘shepherding’ of domestic animals. Only the Jainist beliefs value the lives of all invertebrates. Philosophers are often divorced from the physiological reality of the animals they muse about and science’s traditions of objectivity and the simplest possible explanation of behaviour led to ignorance of invertebrates’ abilities. With the new information about sentience in some of these animals, moral standing and welfare consideration has sometimes been extended to invertebrates, but we have a long distance to go to consider recognition and care of all these 97% of the animals on the planet.

Some peptide-based drugs including oxytocin, vasopressin, ziconotide, pramlintide, nesiritide, and octreotide, contain one intramolecular disulfide bonds. A novel and reusable monodispersed silica nanosphere-supported Pt(IV) complex (SiO2@TPEA@Pt(IV)) was synthesized via a four-step procedure and used for formation of intramolecular disulfide bonds in peptides. TEM and chemical mapping results for the Pt(II) intermediates and for SiO2@TPEA@Pt(IV) show that the silica nanospheres possess a monodisperse spherical structure and contain uniformly distributed Si, O, C, N, Cl, and Pt. The valence state of Pt on the silica nanospheres was characterized by XPS. The Pt(IV) loaded on SiO2@TPEA@Pt(IV) was 0.15 mmol/g, as determined by UV-vis spectrometry. Formation of intramolecular disulfides in six dithiol-containing peptides of variable lengths by use of SiO2@TPEA@Pt(IV) was investigated and the relative oxidation yields were determined by HPLC. In addition, peptide 1 (Ac-CPFC-NH2) was utilized to study the reusability of SiO2@TPEA@Pt(IV). No significant decrease in the relative oxidation yield was observed after ten reaction cycles. Moreover, the structure of SiO2@TPEA@Pt(IV) after being used ten cycles was determined to be similar to its initial one, demonstrating the cycling stability of the complex.

We developed two human induced pluripotent stem cell (hiPSC)/human embryonic stem cell-specific glycan-recognizing mouse antibodies, R-10G and R-17F, using the Tic (JCRB1331) hiPSC line as an antigen. R-10G recognizes a low-sulfate keratan sulfate, and R-17F recognizes lacto-N-fucopentaose-1. To evaluate the general characteristics of stem cell glycans, we used the hiPSC line 201B7 (HPS0063), a prototype iPSC line. Using an R-10G affinity column, an R-10G-binding protein was isolated. The protein yielded a single but very broad band from 480 to 1,236 kDa by blue native gel electrophoresis. After trypsin digestion, the protein was identified as podocalyxin by liquid chromatography/mass spectrometry. According to Western blotting, the protein reacted with R-10G and R-17F. The R-10G positive band was resistant to digestion with glycan-degrading enzymes, including peptide N-glycanase, but the intensity of the band was decreased significantly by digestion with keratanase, keratanase II, and endo-β-galactosidase, suggesting the R-10G epitope to be a keratan sulfate. These results suggest that keratan sulfate-type epitopes are shared by hiPSCs. However, the keratan sulfate from 201B7 cells contained a polylactosamine disaccharide unit (Galβ1-4GlcNAc) at a significant frequency, whereas that from Tic cells consisted mostly of keratan sulfate disaccharide units (Galβ1-4GlcNAc(6S)). In addition, the abundance of the R-10G epitope was significantly lower in 201B7 cells than in Tic cells.

Mass transfer restrictions of scaffolds are currently hindering the development of three-dimensional (3D), clinically viable, and tissue engineered constructs. For this situation, a 3D poly(lactide-co-glycolide)/hydroxyapatite porous scaffold, which was much favorable for transfer of nutrients to and waste products from the cells in the pores, was developed in this study. The 3D scaffold had an innovative structure, including macropores with diameters of 300−450 μm for cell ingrowth and microchannels with diameters of 2−4 μm for nutrition and waste exchange. The mechanical strength in wet state was strong enough to offer the structural support. The typical structure was more beneficial for the attachment, proliferation, and differentiation of rabbit bone marrow mesenchymal stem cells (rBMSCs). The alkaline phosphatase (ALP) activity and calcium (Ca) deposition were evaluated on the differentiation of rBMSCs, and the results indicated that the microchannel structure was very favorable for differentiating rBMSCs into maturing osteoblasts. For repairing rabbit radius defects in vivo, there was rapid healing in the defects treated with the 3D porous scaffold with microchannels, where the bridging by a large bony callus was observed at 12 weeks post-surgery. Based on the results, the 3D porous scaffold with microchannels was a promising candidate for bone defect repair.

The thermal conditions of transitional (ranging from warm to cold) coldwater streams impact the ranges and resource availabilities for biota inhabiting these lotic systems. With ongoing climate change and increasing land modifications, thermal boundaries may shift, altering thermal transition zones and their biotic communities. The objective of this study was to investigate the condition of trout across three forks of the Whitewater River catchment and to investigate factors influencing fish community composition and distribution. Each fork was characterized into three separate sections: headwater (coolwater), middle (warmwater), and lower (coldwater). Springs were identified throughout each fork, with greatest concentrations in the lower sections of each fork. Using single-pass electrofishing, we sampled 61 sites across the three forks in the Whitewater River system (North = 21 sites, Middle = 19, South = 21), and catch statistics were used to calculate diversity, trout abundance, and trout condition. In general, diversity increased, and trout were healthier but less abundant in middle and headwater sections, whereas diversity decreased slightly, trout condition decreased, and trout abundance increased in lower reaches, with changes differing somewhat among forks. Canonical correlation analysis had strong significant correlations showing simpson diversity and condition increase going upstream with high non trout abundance and catch rates while trout catch rates and reach width decrease. The Whitewater River is a catchment exhibiting transitional temperature-pattern characteristics with generally low fish community diversity and trout conditions that range from thin, normal, and robust. Dominated by a changing landscape (agriculture) and intensifying climate change, we may begin to see stream temperatures increase along with species diversity. Understanding how spring temperature influences species composition and distribution can bring potential stressors to light increasing our understanding of thermal conditions and to help mitigate the negative impacts from land use and climate change.

We report the application of a recently proposed approach for modeling biological systems using a maximum entropy production rate principle in lieu of having in vivo rate constants. The method is applied in four steps: (1) a new ODE-based optimization approach based on Marcelin’s 1910 mass action equation is used to obtain the maximum entropy distribution, (2) the predicted metabolite concentrations are compared to those generally expected from experiment using a loss function from which post-translational regulation of enzymes is inferred, (3) the system is re-optimized with the inferred regulation from which rate constants are determined from the metabolite concentrations and reaction fluxes, and finally (4) a full ODE-based, mass action simulation with rate parameters and allosteric regulation is obtained. From the last step, the power characteristics and resistance of each reaction can be determined. The method is applied to the central metabolism of Neurospora crassa and the flow of material through the three competing pathways of upper glycolysis, the non-oxidative pentose phosphate pathway, and the oxidative pentose phosphate pathway are evaluated as a function of the NADP/NADPH ratio. It is predicted that regulation of phosphofructokinase (PFK) and flow through the pentose phosphate pathway are essential for preventing an extreme level of fructose 1, 6-bisphophate accumulation. Such an extreme level of fructose 1,6-bisphophate would otherwise result in a glassy cytoplasm with limited diffusion, dramatically decreasing the entropy and energy production rate and, consequently, biological competitiveness.

Drone imagery has the potential to enrich urban planning and preservation, especially where it converges with the growing creation and use of 3D models. The authors have conducted a systematic literature review of articles published between 2002 and 2022, drawing from reputable academic repositories including Science Direct, Web of Science, and China National Knowledge Infrastructure (CNKI), to identify current gaps in existing research in the application of UAVs to the creation of 3D models in urban planning and preservation. Findings indicate five research shortcomings: limited participation of planning experts, research focus imbalance, lack of usage for special scenarios, lack of integration with smart city planning, and limited interdisciplinary collaboration. The study also acknowledges current limitations with UAV applications and discusses possible countermeasures as well as future prospects.

Uncovering hidden mixture correlation among variables have been investigating in the literature using mixture R-vine copula models. These models are hierarchical in nature. They provides a huge flexibility for modelling multivariate data. As the dimensions increases, the number of the model parameters that need to be estimated is increased dramatically, which becomes along with huge computational times and efforts. This situation becomes even much more harder and complicated in the mixture Regular vine models. Incorporating truncation method with mixture Regular vine models will reduce the computation difficulty for the mixture based models. In this paper, tree-by-tree estimation mixture model is joined with the truncation method, in order to reduce the computational time and the number of the parameters that need to be estimated in the mixture vine copula models. A simulation study and a real data applications illustrated the performance of the method. In addition, the real data applications show the affect of the mixture components on the truncation level.

The oral administration of (R)-3-hydroxybutyl-(R)-3-hydroxybutyrate, allows inducing a beneficial level of blood ketone bodies without the adverse effects due to the adhesion to a ketogenic diet. Several studies documented the therapeutic effectiveness of the (R)-3-hydroxybutyl (R)-3-hydroxybutyrate in treating neurodegenerative diseases as well as its boosting activity of athletic and cognitive performances during prolonged physical exercises. Further studies considering this ketone body ester for therapy of other pathologies are also underway. In the present work, we describe the synthesis of (R)-3-hydroxybutyl-(R)-3-hydroxybutyrate through the enantioselective transesterification of racemic ethyl 3-hydroxybutyrate with (R)-1,3-butanediol catalyzed by immobilized Candida antarctica lipase B (CAL-B). The enantiopure (R)-1,3-butanediol was in turn obtained from the kinetic resolution of the racemate by CAL-B catalyzed acetylation with vinyl acetate. The economy of the synthetic procedure has been improved by recycling the unreacted (S) enantiomers of the ethyl 3-hydroxybutyrate and 1,3-buatnediol after stereochemical inversion achieved by tosylation and SN2 with ammonium acetate. The overall procedure allows to incorporate up to 70% of the starting racemic reagents into the final product.

We used a mixed-method single-case experimental research design to examine the effect of modelling (peer versus non-peer) on exercise self-efficacy in stroke survivors who participated in a community-based exercise program. Quantitative data were obtained using a ABCA design: (A1) no model/baseline 1 (3 weeks); (B) peer model (6 weeks); (C) non-peer model (6 weeks); and (A2) no model/baseline 2 (3 weeks). Four participants completed self-efficacy questionnaires after each weekly session. Qualitative data were obtained using researcher diaries and two semi-structured interviews: after B and A2. Based on quantitative and qualitative results, participants reported higher exercise self-efficacy in the model conditions, with ratings appearing highest for the non-peer model. This finding could be due to a lack of full integration of the peer model and low feelings of similarity. Modelling in general could help people recovering from a stroke increase their exercise self-efficacy, but non-peer models may not be most advantageous.

We introduce the Open Research Knowledge Graph Agriculture Named Entity Recognition (the ORKG Agri-NER) corpus and service for contribution-centric scientific entity extraction and classification. The ORKG Agri-NER corpus is a seminal benchmark for the evaluation of contribution-centric scientific entity extraction and classification in the agricultural domain. It comprises titles of scholarly papers that are available as Open Access articles on a major publishing platform. We describe the creation of this corpus and highlight the obtained findings in terms of the following features: 1) a generic conceptual formalism focused on capturing scientific entities in agriculture that reflect the direct contribution of a work; 2) a performance benchmark for named entity recognition of scientific entities in the agricultural domain by empirically evaluating various state-of-the-art sequence labeling neural architectures and transformer models; and 3) a delineated 3-step automatic entity resolution procedure for the resolution of the scientific entities to an authoritative ontology, specifically AGROVOC that is released in the Linked Open Vocabularies cloud. With this work we aim to provide a strong foundation for future work on the automatic discovery of scientific entities in the scholarly literature of the agricultural domain.

The compatibility between the de Sitter Swampland conjecture and Ho\v{r}ava-Lifshitz $F(\bar{R})$ theories with a flat FLRW metric is studied. We first study the standard $f(R)$ theories and show that the only way in which the dS conjecture can be made independent of $R$ is by considering a power law of the form $f(R)\sim R^{\gamma}$. The conjecture and the consistency of the theory puts restrictions on $\gamma$ to be greater but close to $1$. For the $F(\bar{R})$ theories described by its two parameters $\lambda$ and $\mu$ we use the equations of motion to construct the function starting with an ansatz for the scale factor in the Jordan frame of the power law form. By doing a conformal transformation on the three metric to the Einstein frame we can obtain an action of gravity plus a scalar filed by relating the parameters of the theory. The non-projectable and projectable cases are studied and the differences are outlined. The $F(\bar{R})$ function obtained consists of terms of the form $\bar{R}^{\gamma}$ with the possibility of having negative power terms. The dS conjecture leads to inequalities for the $\lambda$ parameter, in both versions it gets restricted to be greater but close to $1/3$. For the general case in which $\mu$ and $\lambda$ are considered as independent, the action contains an extra term but we propose that the conjecture is still applicable. Once again the non-projectable and projectable cases are studied. The $F$ function obtained has the same form as before, the consistency of the theory and the dS conjecture lead to a set of inequalities on both parameters that are studied numerically. In all cases $\lambda$ is restricted by $\mu$ around $1/3$ and we obtain $\lambda\to1/3$ if $\mu\to0$. Finally we consider the $f(R)$ limit $\mu,\lambda\to1$ and we obtain consistent results.

In this work, we explore a the different forms of a new type of modified gravity, namely f(φ) gravity. We construct the Big Rip type for the energy density and the curvature of the universe. We show that dark energy is a result of the transformation of the field φ mass (dark matter) to energy. In addition, we provide that Ω_{m}≈0,050, Ω_{DM}≈0,2, Ω_{DE}≈0,746, is in excellent agreement with observation data. We explore a generalized formalism of braneworld modified gravity. We also construct a new field equations, which generalize the Einstein field equations. We provide a relation between the extra dimension in 3-brane with the vacuum energy density. We show that the energy density of matter depends directly on the number of dimensions. We manage to find the value of the Gauss-Bonnet coupling α=1/4 which is a good agreement with the results in the literature, this correspondence creates a passage between f(R) gravity and Gauss-Bonnet gravity, this comparison leads to a number of bulk dimensions equal to D=10¹²¹+4.

Family support is offered to Australian parents of young children using a mix of targeted and universal child and family health services. A feature of the universal services is the ability for nurses to work in partnership with families and to offer flexibility depending on need. This model of progressive universalism relies on the voluntary engagement of families, including families with complex needs. In this study, the capacity to engage and retain families, including those at risk for child maltreatment and family violence, was examined. Child and Family Health Nurses (n=129) participated in a pragmatic, multilevel mixed-methods study using the McCurdy and Daro (2001) Integrated Theory of Parent Involvement. A questionnaire was used in the first phase of the study to collect the quantitative data. Focus groups were then held with 27 participants recruited from phase one. Both homogeneous and heterogenous practices identified from the questionnaire were the focus of the discussions. Three phases of practice were identified and described: enrolment, retention and conclusion of the nurse-parent relationship and are presented and discussed in this paper. The retention of families with complex needs relies on flexible, advanced, and multidimensional nursing practices.

Extreme heat is a climate, public health, and environmental justice issue. This case study examined public transit exposure and vulnerability to extreme heat by investigating the microenvironment, land cover characteristics, and social vulnerability of heat-vulnerable bus stops in Knoxville, Tennessee. The community’s temperature and Heat Index information, bus stop point data, land cover characteristics data, and the microenvironment of bus stops (i.e., trees and shelters) were processed and mapped with ArcGIS Pro. The pictures of the microenvironment of the bus stop were collected from Google Maps, and the social vulnerability of the area where the bus stops are located was investigated by analyzing the Center for Disease and Prevention's Social Vulnerability Index. Results found that the most heat-vulnerable bus stops were concentrated in West Knoxville, South, North, Northeast, and Northwest Knoxville. In addition, the most heat-vulnerable bus stops were concentrated in commercial complexes and areas a large number of systematically marginalized populations reside.

Evidence supports an association between low magnesium (Mg) intake and coronary heart disease and between Mg intake and endothelial function. The aim of this study was to assess the effect of one week of Mg supplementation on endothelial function, assessed by flow mediated dilatation (FMD). Nineteen healthy men and women completed this cross-over pilot study in which participants were randomised to take an over-the-counter magnesium supplement for one week or to follow their usual diet. Weight, FMD and blood pressure (BP) were taken on completion of each intervention and 24hour urine collections and blood samples were taken to assess compliance. Baseline serum Mg was within normal range for all participants. Urinary Mg and urinary magnesium-creatinine ratio (Mg/Cr) significantly increased between interventions, (p = 0.03, p = 0.005 respectively). No significant differences in FMD or BP were found between the interventions. A significant negative correlation was seen between age and FMD (r = -0.496, p = 0.031). When adjusted for age, saturated fat was negatively associated with FMD (p = 0.045). One week of Mg supplementation did not improve FMD in a healthy population.

Context: A clinical video telehealth (CVT) program was implemented improve access and quality of dementia care to patients and their caregivers in rural areas. The program was offered as part of an established dementia clinic/geriatric primary care clinic in collaboration with five community-based outpatient clinics (CBOC’s) affiliated with the Tennessee Valley Healthcare System (TVHS) in middle Tennessee. Telehealth support was provided by a physician – social worker team visit. Methods: Telehealth training and equipment were provided to clinic personnel, functioning part-time with other collateral clinical duties. Patients and caregivers were referred by primary care providers and had an average of 1 to 2 CVT encounters originating at their local CBOC lasting 20 to 30 minutes. Clinical characteristics and outcomes of patients and caregivers receiving CVT support were collected by retrospective electronic medical record (EMR) review. Results: Over a 3-year period 45 CVT encounters were performed on patient-caregiver pairs, followed for a mean of 15 (1-36) months. Some 80% patients had dementia confirmed and 89% of these had serious medical comorbidities, took an average of 8 medications, and resided at a distance of 103 (76-148) miles from the medical center. Dementia patients included 33% with late stage dementia, 25% received additional care from a mental health provider, 23% took antipsychotic medications, 19% transitioned to a higher level of care, and 19% expired an average of 10.2 months following consultation. Caregiver distress was present in 47% of family members. Consult recommendations included 64% community-based long-term care services and supports (LTSS), 36% medications, and 22% further diagnostic testing. Acceptance of the CVT encounter was 98%, with 8770 travel miles saved. Conclusion: CVT is well received and may be helpful in providing dementia care and supporting dementia caregivers to obtain LTSS for high-need older adults in rural areas.

Fructose in beverages has adverse effects on lipids, glucose and insulin sensitivity after acute and chronic ingestion. There is limited data showing that chronic consumption of fructose in solid foods has harmful effects. We hypothesized that a moderate amount of fructose compared with sucrose in solid food consumed for a month would not adversely influence fasting or postprandial lipids and glucose after an acute fat and carbohydrate load. Twenty-five men and women with prediabetes and/or obesity and overweight consumed in random order two acute test meals of muffins sweetened with either fructose or sucrose, followed by 4-week chronic consumption of 42g/day of either fructose or sucrose in low fat muffins after which the 2 meal tests were repeated. Subjects were randomised to sugar type in the chronic feeding period. Sugar type had no effect on the incremental area under the curve for triglyceride or uric acid at either time point (P=0.4 and P=0.9). There was no overall difference between meal tests at baseline and after 1 month and no effect of consuming sucrose or fructose muffins for 1 month. Fasting triglyceride increased after chronic consumption of fructose by 0.31±0.37 mmol/L compared with sucrose in people with IFG/IGT only (P=0.004). Fructose at a moderate intake of <10% of energy in solid food has no different effects on postprandial triglyceride and uric acid compared with sucrose although fasting triglyceride was increased in people with IFG/IGT after 1 month of fructose muffins suggesting the need for caution.

Rivers across the globe experience and respond to changes within the riparian corridor. Disturbance of the riparian corridor can affect warmwater, intermediate, and coldwater streams, which can negatively influence instream physical structure and biological communities. This study focused on assessing the influence of riparian habitat on instream structure within the Whitewater River, a coldwater stream system within an agricultural watershed in southeastern Minnesota, USA. Twenty variables (riparian, n = 9; instream, n = 11) were measured at 57 sites across three forks of the Whitewater. Canonical correlation detected significant associations between riparian and instream variables across the river forks, and indicated that wider riparian buffers, more bank grass and shrubs, longer overhanging vegetation, limited bare soil and more rocks on banks were significantly associated with increased instream cover, high levels of coarse substrates with reduced embeddedness, increased pool habitats, and reduced fine sediments. In contrast, excessive fine sediments, lack of riffle habitat, reduced coarse substrates, and high width to depth ratios indicative of impaired instream habitat were associated with narrow riparian buffers and high percentages of bare soil on banks. Riparian corridors have the capacity to enhance and protect physical instream habitat and overall ecosystem health when managed properly. Wide, grassy riparian corridors with stable banks, overhanging vegetation, and limited shade from trees should protect and/or enhance instream physical habitat, providing the structural diversity favored by aquatic communities.

Bio-absorbable stents are a novel tool which relieve stenosis and then resorb as the patient grows, avoiding obligatory re-intervention. This case describes the novel use of an iron bio-absorbable stent in a child with surgically repaired Tetralogy of Fallot who post-operatively developed a severely stenotic right ventricular outflow tract.

A wealth of Full Waveform (FW) LiDAR data are available to the public from different sources, which is poised to boost the extensive application of FW LiDAR data. However, we lack a handy and open source tool that can be used by potential users for processing and analyzing FW LiDAR data. To this end, we introduce waveformlidar, an R package dedicated to FW LiDAR processing, analysis and visualization as a solution to the constraint. Specifically, this package provides several commonly used waveform processing methods such as Gaussian, adaptive Gaussian and Weibull decompositions, and deconvolution approaches (Gold and Richard-Lucy (RL)) with users’ customized settings. In addition, we also developed functions to derive commonly used waveform metrics for characterizing vegetation structure. Moreover, a new way to directly visualize FW LiDAR data is developed through converting waveforms into points to form the Hyper Point cloud (HPC), which can be easily adopted and subsequently analyzed with existing discrete-return LiDAR processing tools such as LAStools and FUSION. Basic explorations of the HPC such as 3D voxelization of the HPC and conversion from original waveforms to composite waveforms are also available in this package. All of these functions are developed based on small-footprint FW LiDAR data, but they can be easily transplanted to the large footprint FW LiDAR data such as Geoscience Laser Altimeter System (GLAS) and Global Ecosystem Dynamics Investigation (GEDI) data analysis. It is anticipated that these functions will facilitate the widespread use of FW LiDAR and be beneficial for better estimating biomass and characterizing vegetation structure at various scales. The package and code examples can be found at https://github.com/tankwin08/waveformlidar.

Quasi-solid composited electrolytes were produced by LiFSI initiated polymerized poly-(Dioxolane) (PDOL) with garnet-LLZO (Li7La2Zr3O12) nanofibers and used in lithium-metal batteries. Linear sweep voltammetry shows that the initial oxidation voltage of 4.6 V for Gel-10% (G10, 10% wt. LLZO in PDOL) vs Li/Li+. EIS test of stainless steel// stainless steel symmetric cells for Gel-1% (G1), Gel-5% (G5) and Gel-10% (G10) show ion conductivity (5*10-5 S/cm). Li/G10/Li symmetric cells have stable stripping-plating cycling performance over 1300 hours continuously with the current density of 0.1 mA/cm2 at 25 oC, indicating a good interface contact and stable lithium-ion transport pathway through the composite electrolytes. LFP/G10/Li batteries have stable charge-discharge plateau, low polarization voltage of 0.07-volt, energy efficiency of 95% and coulombic efficiency of ~99% at current density of 26.3 mA/g at 25 oC for over 100 cycles.

Identification and segmentation of rock particles is very important in geology, mining, engineering construction, and environmental monitoring. Traditional methods for recognizing the rock particle characteristics are time-consuming, labor-intensive, and limited by the geographical scope of the sampling sites, which makes it more difficult to represent the spatial distribution of the rock particles accurately. Recent advancements in deep learning techniques offer promising solutions to automate this process. This study aims at utilizing state-of-the-art (SOTA) Mask R-CNN deep learning algorithm from the Detectron2 framework, to capture global features of rocks that will enable the recognition of rock particles more efficiently, just from having the rock images. These images are subject to image processing techniques such as a Gaussian filter, to denoise and smoothen the image, and an Illumination Adaptive Transformer (IAT) framework, to adjust the lighting exposure; all of which add to improve the quality of the image dataset. Afterward, the Mask R-CNN and Detectron2 models are utilized in training the images using transfer learning. Experimental results from evaluating the performance of the proposed algorithms showcase the effectiveness of the approach, thereby highlighting its potential to revolutionize rock particle segmentation across various domains.

(R)-(+)-3,5-Dinitro-N-(1-phenylethyl)benzothioamide 1 is a potential chiral solvating agent (CSA) for the spectral resolution of enantiomers by 1H NMR spectroscopy. The single enantiomer of 1 was synthesized from commercially (R)-(+)-a-methylbenzylamine 2 in two-steps with 85% yield.

We study certain function algebras and their operator algebra completions on r-discrete abelian groupoids, the corresponding conditional expectations, maximal abelian subalgebras (masa) and eigen-functionals.

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

Symmetry concepts in parametrized dynamical systems may reduce the number of external parameters by a suitable normalization prescription. If, under the action of a symmetry group G, parameter space A becomes a (locally) trivial principal bundle, A ~ A/G x G, then the normalized dynamics only depends on the quotient A/G. In this way, the dynamics of fractional variables in homogeneous epidemic SI(R)S models, with standard incidence, absence of R-susceptibility and compartment independent birth and death rates, turns out to be isomorphic to (a marginally extended version of) Hethcote's classic endemic model, first presented in 1973. The paper studies a 10-parameter master model with constant and I -linear vaccination rates, vertical transmission and a vaccination rate for susceptible newborns. As recently shown by the author, all demographic parameters are redundant. After adjusting time scale, the remaining 5-parameter model admits a 3-dimensional abelian scaling symmetry. By normalization we end up with Hethcote's extended 2-parameter model. Thus, in view of symmetry concepts, reproving theorems on endemic bifurcation and stability in such models becomes needless.

Previous studies demonstrate the critical importance of non-coding RNAs interfacing with chromatin-modifying machinery resulting in promoter-enhancer-based gene regulation and raise the possibility that many other enhancer-like RNAs may operate via similar mechanisms. Critically, more than 80% of the disease-linked variations identified in genome-wide studies are located in the non-coding regions of genomes, especially non-coding RNA, suggesting non-coding RNAs are relevant to disease. Thus, a critical path forward for understanding non-coding RNAs' role, especially long non-coding RNAs, is to understand the genomic regions' transcriptional regulation, especially non-coding regions. Here, we developed a user-friendly R package called SomaGene for studying and identifying enhancer-like non-coding RNAs with enriched somatic mutations in the cancer genome. SomaGene accepts different genomic variants (whole genome/exome somatic point mutations, structural variations, copy number variations) to identify those RNAs that significantly mutated in diseases (e.g., cancer). It then uses multiple publicly available genomics and epigenetics datasets including ENCODE epigenomics annotations, FANTOM5 tissue-specific expression profiles, disease-associated genome-wide association SNPs, and tissue-specific eQTL pairs to identify those RNAs with potentially enhancer function. SomaGene, as a powerful R package, can provide the opportunity to cancer scientists to study the roles of non-coding RNAs in different cancer genomes.

The authors previously found a model of universal quantum computation by making use of the coset structure of subgroups of a free group $G$ with relations. A valid subgroup $H$ of index $d$ in $G$ leads to a \lq magic' state $\left|\psi\right\rangle$ in $d$-dimensional Hilbert space that encodes a minimal informationally complete quantum measurement (or MIC), possibly carrying a finite \lq contextual' geometry. In the present work, we choose $G$ as the fundamental group $\pi_1(V)$ of an exotic $4$-manifold $V$, more precisely a \lq small exotic' (space-time) $R^4$ (that is homeomorphic and isometric, but not diffeomorphic to the Euclidean $\mathbb{R}^4$). Our selected example, due to to S. Akbulut and R.~E. Gompf, has two remarkable properties: (a) it shows the occurence of standard contextual geometries such as the Fano plane (at index $7$), Mermin's pentagram (at index $10$), the two-qubit commutation picture $GQ(2,2)$ (at index $15$) as well as the combinatorial Grassmannian Gr$(2,8)$ (at index $28$) , (b) it allows the interpretation of MICs measurements as arising from such exotic (space-time) $R^4$'s. Our new picture relating a topological quantum computing and exotic space-time is also intended to become an approach of \lq quantum gravity'.

Magnesium (Mg) deficiency may be a catalyst in the process of endothelial dysfunction, an early event in the pathogenesis of atherosclerosis. The aim was to determine the acute effect of an oral Mg supplement compared to control on endothelieal function assessed by flow-mediated-dilatation (FMD). Nineteen participants (39 years, body mass index (BMI) 22.9kg/m2) completed this randomised cross-over study. Blood pressure (BP) and FMD were measured and blood samples taken before participants drank 200ml water with or without an over the counter Mg supplement (450mg and 300mg for men and women). Measurements were repeated at 60 and 120 minutes. There was a statistically significant two-way interaction between treatment and time on serum Mg (p = .037). A difference of -0.085mm in FMD was observed 60 minutes post drink in the control group compared to baseline FMD, and no difference was observed in the supplement group compared to baseline. Despite the non-significant interaction between treatment and time on FMD, the difference seen in the control group and the lack of change in the supplement group at 60 minutes post-drink suggests that Mg may attenuate the reduction in FMD post-prandially.

Pneumonia remains a major cause of morbidity and mortality worldwide, especially during COVID-19 pandemic. With the significant global health burden that pneumonia poses, it is es-sential to improve therapeutic and management strategies. The increasing emergence of antibiotic resistant bacterial strains limits options for effective antibiotic use. New antibiotics for treatment of pneumonia may address deficits in current antimicrobial drugs, with an ability to cover both typical, atypical, and resistance pathogen. Several of these newer drugs also have structural characteristics that allow for a decreased propensity in development of bacterial resistance. Po-tential use of stem cell therapies in place of corticosteroid treatments may also offer an im-provement in patient outcomes. Human mesenchymal stem cell treatments have shown efficacy and safety in treating COVID-19 induced pneumonia. Combined treatment with both stem cells and antibiotics in pneumonia in a rabbit model has also shown significantly increased efficacy in comparison to antibiotic treatment alone, presenting yet another possible route for a novel strategy in treating pneumonia, though additional future studies are necessary before clinical implementation. While pneumonia remains a major disease of concern, having newer approved antibiotics as well as novel therapies such as stem cell treatments in the pipeline offers clinicians more options in effectively treating pneumonia.

In this article, we give a brief review of the origin of the neutrino mass in some interesting non-linear supersymmetric models with R-symmetry. These models are able to address and solve the most important problems of the particle physics and provide mechanisms for neutrino mass generation and their mixing parameters in agreement with the current experimental data. Their prediction could be experimentally tested in the near future by collider experiments.

This paper presents a script that classify spatial patterns of residential urban growth using a morpho-structural approach. The script performs a combination of variography analysis and morphological closings over buildings possessing a residential function in 2002 and 2017 within a region located in southern France named Centre-Var. The different bounding regions then allow classifying new residential buildings into different categories according to their degrees of clustering/scattering and to their locations regarding existing urban areas. Preliminary results show that this protocol is able to provide useful insights regarding the degree of contribution of each new residential building to different patterns of urban growth (clustered infill, scattered infill, clustered edge-expansion, scattered edge-expansion, clustered leapfrog and scattered leapfrog). Open-access to the script and to the test region data is provided.

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.

Insufficient physical activity (PA) is associated with low cardiorespiratory fitness, which favors cardiovascular and other non-communicable diseases. Besides, it evidentially affects mental health. Considering the WHO PA guidelines, CrossFit® represents a versatile exercise program, combining aerobic and resistance training with mobility and could help lowering disease incidences among sedentary people. Yet, long-term CrossFit research is sparse. We conducted a nine-months intervention (≥ 2 CrossFit workouts/week) in sixteen beginners (14 males, 35  6.8 years, 180  8.6 cm, 85. 5  19.1 kg). As primary endpoint, VO2max was assessed at baseline, after four, and nine months. A repeated-measures ANOVA and pearson correlation were conducted. Well-being was investigated by WHO-5-index pre- and post-intervention. For exploratory purpose, body composition was tracked. Main outcome was an 11.5 % VO2max improvement with large effect (p < .01, η_p^2 = .27). Strong negative correlations between baseline VO2max and its progression after nine months (p = .006, r = -.654) were found. Well-being increased by 8.7 % (p = .024, d = .51). Body composition improved without statistical significance. Resting metabolic rate increased by 2.2 % (p = .042). This study reveals the potential of CrossFit to enhance physiological and psychological health in beginners. For more robust results, bigger sample sizes with higher proportion of women are needed.

Background: Fiber-reinforced composites (FRCs) have been proposed as an alternative to traditional metal alloys for the realization of frameworks in full-arch implant supported prostheses. The aim of the present in vitro study was to evaluate the deflection under load of seven prostheses endowed with frameworks made of different materials, including different types of fiber reinforced composites (FRCs). Methods: A master cast with four implant analogues in correspondence of the two lateral incisors and the two first molars was used to create full-arch fixed prostheses with the same shape and different materials. Prostheses were made in different materials (framework+veneering material): gold alloy+resin (Au+R), titanium+resin (Ti+R), FRC with multi-directional carbon fibers+resin (ICFRC+R), FRC with unidirectional carbon fibers+composite (UCFRC+C), FRC with glass fibers+resin (GFRC+R), FRC with glass fibers+composite (GFRC+C), resin (R, full-acrylic prosthesis). Flexural tests were conducted using Zwick/Roell Z 0.5 machine and the deflection of the lower surface of the prosthesis was measured in order to obtain load/deflection graphs. Results: Greater rigidity and less deflection were recorded for UCFRC+C, GFRC+C, followed by Ti+R, and Au+R. The greatest deformations were observed for resin alone, ICFRC+R and GFRC+R. The results were slightly different in the incisal region probably due to the greater amount of veneering material in this area. Conclusions: When used to realize full-arch frameworks, Au and Ti allow a predictable mechanical behavior with gradual deformations with increasing load. UCFRC also demonstrated good outcomes and less deflection than ICFRCs when loaded. The GFRC full-arch framework may be a valid alternative, however showed greater deflections. Further studies are needed in order to evaluated how different prosthesis design and material thickness might affect the outcomes.

This paper reports the findings from a pilot study designed to explore the barriers, facilitators and similarities with the delivery and implementation of two distinct models of Advance Care Planning (ACP) documentation for older adults in their last year of life used by health care professionals in their clinical practice. PACe (Proactive Anticipatory Care Plan): a GP led model and PEACE (Proactive Elderly Persons’ Advisory CarE): a nurse led model with community geriatrician oversight were used by participants in their clinical practice. Telephone interviews were conducted with general practitioners (GPs) to explore their views of using the PACe tool. Hospital admission avoidance matrons took part in face to face interviews and care staff employed in private residential care homes took part in individual telephone interviews to explore their views of using the PEACE tool. GPs and admission avoidance matrons were employed by Clinical Commissioning Groups (CCGs) and all study participants were recruited from the South East of England where data collection took place in 2015. Nine telephone interviews and two face-to-face interviews (one joint and one individual) were conducted with twelve participants. The data was analysed thematically. Participants highlighted the similarity of both tools in providing focus to ACP discussions to inform individual end-of-life care preferences. The importance of relationships was a pivotal theme-established, trusting inter-professional relationships to enable multidisciplinary teamwork and a prior relationship with the older person (or their proxy in the case of cognitive impairment) to enable conversations of this nature. Using both tools enabled participants to think critically and reflect on their own practice was another theme identified. Notwithstanding participants’ views to improve the layout of both tools, using a paper-based approach to deliver streamlined ACP and end-of-life care was a theme to emerge as a barrier which focused on the problems with access to paper-based documentation, accuracy and care co-ordination in the context of multidisciplinary team working. The value of technology in overcoming this barrier and underpin ACP as a means to help simplify service provision, promote integrated professional practice and provide seamless care was put forward as the solution.

Judgment bias tasks assess optimism and pessimism through responses to ambiguous stimuli. Optimistic individuals anticipate receiving a reward whereas pessimistic individuals anticipate a lack of reward when interacting with ambiguous stimuli, which is reflected in approach time. Researchers have used these tests to assess animals’ reactions to assumed positive and negative contexts, but rarely to assess the effects of participation in ambassador programs. We tested two ambassador animals: a domestic chicken and a red tegu after exposure to zoo visitors. Once they learned that a container on the left contained food whereas a container on the right contained no food, we introduced an ambiguous container equidistant from the left and right locations. We assessed the chicken’s judgment biases when she was perched or held. We assessed the tegu’s judgment bias when visitors were allowed to touch him or not. The chicken displayed pessimism whether it was held or perched, but the tegu displayed pessimism only when no visitor touch occurred, suggesting that touch may not be aversive to the tegu, but that interacting with visitors may have deleterious effects on the chicken. We encourage the use of these tests to inform the use of animals in ambassador programs.

Background and Aims: Paramedics attend an unprecedented number of drug poisoning events daily in British Columbia (BC), Canada due to the ongoing public health crisis related to an increasingly toxic and unregulated supply of illicit drugs. Paramedics have the potential to support alternative models of care to reduce harm, but their perspectives towards harm reduction initiatives are polarized. Understanding the drug-related substance use content in paramedic curriculum documents is important for deploying effective harm mitigating programs. The objective of this study was to understand what drug-related substance use content currently exists within paramedic curriculum documents in British Columbia. Methods: We performed a document analysis of curriculum documents in BC’s paramedic training institutions, the primary program textbook, and the 2011 National Occupational Competency Profile (NOCP). We used the Checklist for Assessment and Reporting of Document Analysis (CARDA) tool to perform our analysis. We analysed and coded documents both inductively and deductively and subsequently combined, refined, and used the codes to inform the development of themes via reflexive thematic analysis. Results: Of the 44 documents analysed, 22 included codes relevant to the research questions. Paramedics are primarily taught to care for people who use drugs in an acute drug-poisoning response only, with little consideration of holistic care, and no meaningful mention of harm reduction. Some stigmatizing language was found within the content. Conclusions: Many opportunities to introduce holistic models of care for people who use drugs along the entire continuum of care are unaddressed by paramedic curriculum documents in BC. Curriculum developers should include people who have lived and living experience of drug use in the co-design of educational programs involving their care. Further qualitative analyses are required to evaluate the relationship between paramedic education and provider-based stigma.

Fluid flow and chemokine gradients play a large part in not only regulating homeostatic processes in the brain, but also in pathologic conditions by directing cell migration. Tumor cells in particular are superior at invading into the brain resulting in tumor recurrence. One mechanism that governs cellular invasion is autologous chemotaxis, whereby pericellular chemokine gradients form due to interstitial fluid flow (IFF) leading cells to migrate up the gradient. Glioma cells have been shown to specifically use CXCL12 to increase their invasion under heightened interstitial flow. Computational modeling of this gradient offers better insight into the extent of its development around single cells, yet very few conditions have been modelled. In this paper, a computational model is developed to investigate how a CXCL12 gradient may form around a tumor cell and what conditions are necessary to affect its formation. Through finite element analysis using COMSOL and coupled convection-diffusion/mass transport equations, we show that velocity (IFF magnitude) has the largest parametric effect on gradient formation, multidirectional fluid flow causes gradient formation in the direction of the resultant which is governed by IFF magnitude, common treatments and flow patterns have a spatiotemporal effect on pericellular gradients, exogenous background concentrations can abrogate the autologous effect depending on how close the cell is to the source, that there is a minimal distance away from the tumor border required for a single cell to establish an autologous gradient, and finally that the development of a gradient formation is highly dependent on specific cell morphology.

Growing evidence about the negative socio-environmental consequences of plastic pollution led to various initiatives for better plastic scrap governance and its trade. At the same time, an examination of recent data shows that plastic scrap represents only a fraction of recyclable materials which are traded internationally and are also subject to similar problems of cross-border environmental governance. A limited analysis comparing plastics, textiles, paper and ferrous metals suggests that ongoing momentum for improvement of plastic scrap governance and circularity should also be framed to consider other types of secondary materiais.

Meta-analysis of plant sterol supplement studies suggests an 8% lowering of LDL cholesterol for 2 to 2.5g/day of plant sterols. Cereal foods have been rarely tested and one study showed a lower LDL lowering of 5.4% with 1.6g of plant sterol in breakfast cereal. We aimed to test a breakfast wheat biscuit with 2g of plant sterols in a single serve of two wholegrain wheat breakfast cereal biscuits. Fifty volunteers with a total cholesterol of >5.5mmol/L were recruited for a randomised crossover study with two 4-week periods with no washout of which 45 successfully completed the study. After exclusion of four outliers the difference in LDL cholesterol between standard wholegrain wheat breakfast cereal biscuit and plant sterol-enriched wholegrain wheat breakfast cereal biscuit was 0.23 mmol/L or 5.6% (P=0.001) with a 95% confidence interval of 2.4-8.9%. Men and daily cereal consumers had greater responses 9.8% vs 3.6% and 7.2% vs 3.8% respectively (P<0.05). The LDL lowering effect of 2g of plant sterol enriched from one serve of wholegrain wheat breakfast cereal biscuit was not significantly different from other food products delivering 2-2.5g of plant sterols daily. Regular cereal consumers have a better response.

Fibrosis is a prevalent and detrimental condition associated with various diseases with a high impact on global morbidity and mortality rates. Despite its diverse causes and affected organs, common underlying mechanisms drive the development and progression of the disease. These mechanisms include an exaggerated inflammatory response, excessive activation of fibroblasts, and abnormal tissue remodeling following severe or repetitive tissue injury. Although significant advancements have been achieved to enhance our understanding of fibrosis, there is still a gap between identifying potential antifibrotic targets and successfully translating them into effective clinical interventions. Novel approaches that target specific cellular and molecular processes involved in fibrosis hold promise for reducing the pathological consequences of the disease. Understanding the pathogenesis and clinical implications of fibrotic diseases is crucial for developing effective therapeutic strategies and improving patient outcomes. In this review, we introduce the concept of fibrosis, discuss the mechanisms by which it arises, and explore existing and emerging therapeutic approaches in development.

Telemedicine is the use of Information and Communication Technology (ICT) for clinical health care from a distance. The exchange of radiographic images and electronic patient health information/records (ePHI/R) for diagnostic purposes has the risk of confidentiality, ownership identity, and authenticity. In this paper, a data hiding technique for ePHI/R is proposed. The color information in the cover image is used for key generation, and stego-images are produced with ideal case. As a result, the whole stego-system is perfectly secure. This method includes the features of watermarking and steganography techniques. The method is applied to radiographic images. For the radiographic images, this method resembles watermarking, which is an ePHI/R data system. Experiments show promising results for the application of this method to radiographic images in ePHI/R for both transmission and storage purpose.

A facilitative transport system exists on the blood brain barrier (BBB) that has been tacitly assumed to be a path for glutamate entry to brain. But glutamate is a non-essential amino acid whose brain content is much greater than plasma, and studies in vivo show that glutamate does not enter brain in material quantities except in those small regions with fenestrated capillaries (circumventricular organs). The situation became understandable when luminal (blood facing) and abluminal (brain facing) membranes were isolated and studied separately. Facilitative transport of glutamate and glutamine exist only on the luminal membranes whereas Na+-dependent transport systems for glutamate, glutamine and some other amino acids are present only on the abluminal membrane. The Na+-dependent cotransporters of the abluminal membrane are in a position to actively transport amino acids from the extracellular fluid (ECF) into the endothelial cells of the BBB. These powerful secondary active transporters couple the energy of the Na+-gradient to move glutamate and glutamine into the ECF whereupon glutamate can exit to blood on the luminal facilitative glutamate transporter. Glutamine may also exit brain on a separate facilitative transport system that exists on the luminal membranes or glutamine can be hydrolyzed to glutamate within the BBB thereby releasing ammonia that is freely diffusible. The γ-glutamyl participate cycle participates indirectly by producing oxoproline (pyroglutamate) that stimulates almost all secondary active transporters yet discovered in the abluminal membranes of the BBB.

We investigate and discuss in detail the structure of the restricted singular value decomposition for a tensor triplet under t-product (T-RSVD). The algorithm is provided with a numerical example illustrating the main result. For applications, we consider color image watermarking processing with T-RSVD.

A Friedmann-Lemaitre-Robertson-Walker space-time model with all curvatures k=0,±1 is explored in f(R,T) gravity. The solutions are obtained via the parametrization of the scale factor that leads to a model transiting from a decelerated universe to an accelerating one. The physical features of the model are discussed and analysed.

Single image deraining (SID) has shown its importance in many advanced computer vision tasks. Though many CNN based image deraining methods have been proposed, how to effectively remove raindrops while maintaining background structure remains a challenge that needs to be overcome. Most of the deraining work focuses on removing rain streaks, but in heavy rain images, the dense accumulation of rainwater or the rain curtain effect significantly interferes with the effective removal of rain streaks, and often introduces some artifacts that make the scene more blurry. In this paper, we propose a new network structure R-PReNet for single image deraining with good background structure maintaining. This framework fully utilizes the cyclic recursive structure of PReNet. Moreover, we introduce residual channel prior (RCP) and feature fusion modules for better deraining performance by focusing on background feature information. Compared with the previous methods, our method has significantly improvement effect on the rainstorm image with the artifacts removing and good visual detail restoring.

We analyze the behavior of relativistic spherical objects within the context of modified $f(R,T)$ gravity considering Tolman VI spacetime, where gravitational lagrangian is a function of Ricci scalar(R) and trace of energy momentum tensor(T) i.e,$ f(R,T)= R+ 2\beta T$, for some arbitrary constant $\beta$. For developing our model, we have chosen $\pounds_{m} = -p$, where $ \pounds_{m}$ represents matter lagrangian. For this investigation, we have chosen three compact stars namely PSR J1614-2230 [Mass=(1.97$\pm$ 0.4)M$_\odot$; Radius= 9.69$_{-0.02} ^{+0.02}$ Km] ,Vela X-1 [Mass=(1.77$\pm$ 0.08)M$_\odot$; Radius= 9.560$_{-0.08} ^{+0.08}$ Km] and 4U 1538-52 [Mass=(9.69)M$_\odot$; Radius= 1.97 Km]. In this theory the equation of pressure isotropy is identical to standard Einstein's theory. So all known metric potential solving Einstein's equations are also valid here. In this paper, we have investigated the effort of coupling parameter ($\beta$) on the local matter distribution. Sound of speed and adiabatic index are higher with grater values of $\beta$ while on contrary mass function and gravitational redshift are lower with higher values of $\beta$ . For supporting the theoretical results, graphical representation are also employed to analyze the physical viability of the compact stars.

Diabetes Mellitus (DM) is a chronic metabolic disease consisting of Type 1 or Type 2 diabetes. Although treatment of Type 1 diabetes primarily involves insulin therapy, inhibitors of sodium glucose co-transporters (SGLT’s) are a promising new therapeutic. Of particular interest are the two family members, SGLT1 and SGLT2 that collectively contribute to 100% of filtered glucose reabsorption within the kidneys. Consequently, sole SGLT2 inhibitors (SGLT2i) and dual SGLT1/2 inhibitors (SGLT1/2i) contribute to reducing blood glucose levels by reducing glucose reabsorption and promoting glucosuria and natriuresis. Research from our team on SGLT2i, showed that there is a compensatory mechanism whereby SGLT1 is upregulated. This therefore may warrant the combined use of SGLT1/2i. Our in vitro results demonstrated that whilst both the sole SGLT2i empagliflozin (EMPA) and dual SGLT1/2i sotagliflozin (SOTAG) significantly reduce glucose uptake within HK2 cells, the latter was more effective. In addition, our in vitro results indicate significantly more pronounced upregulation of SGLT1 protein with EMPA compared to SOTAG. Our in vivo mechanistic findings demonstrated that SGLT1/2i significantly increased renal SOD1 levels, whilst SGLT2i significantly elevated renal SOD2 levels. Therefore, our study highlighted that SGLT2i and SGLT1/2i differentially regulate protective anti-oxidant proteins in the kidney.

Wastewater-Based Epidemiology (WBE) is currently used to monitor not only the spread of the pandemic virus SARS-CoV-2 but also for other viruses in endemic conditions, particularly in the absence of syndromic surveillance. Continuous monitoring of sewage requires high costs and significant time investment, highlighting the need for standardized methods and structured monitoring strategies. In this context, we conducted weekly wastewater monitoring in northwestern Italy, targeting Human Adenovirus (HAdV), Norovirus Genogroup II (NoVggII), Enterovirus (EV), and SARS-CoV-2. Samples collected at the entrance of treatment plants were concentrated using PEG/NaCl precipitation and viral nucleic acids were extracted and detected by real-time (RT-)qPCR. NoVggII resulted the most identified target (84.4%), followed by HAdV, SARS-CoV-2, and EV. Only HAdV and EV exhibited seasonal peaks in spring and summer. SARS-CoV-2 results compared with data previously collected in the same study area (February 2021 to September 2021) revealed a shift from an epidemic to a pandemic status, likely due to the evolution of variants. In conclusion, WBE, using standardized methods and an efficient monitoring strategy, proves valuable for virus surveillance in pandemic and epidemic scenarios, enabling the identification of temporal-local distribution patterns that are useful for making informed public health decision.

The main contribution of this paper is to develop a graphical tool to evaluate the suitability of a candidate parametric model to fit a data set. The practical motivation is to check the adequacy of the so called SAINT model proposed in Jarner and Kryger (2011). This model has been implemented in practice by an important European pension fund concerned with setting annuity reserves for all current or former employees of Denmark. So, one particular relevant question is whether this mortality model is actually fitting old-age. Our graphical test can be described as follows. First we transform the data by means of the parametric model which is being evaluated. Should the model be correct, the transformed data will be in accordance with an Exponential distribution with rate 1. Then we construct a family of local linear hazard estimates based on the data on the transformed scale. Finally we use the statistical tool SiZer to assess the goodness-of-fit of the Exponential distribution to the data on the transformed scale. If the model is correct the SiZer map should not reveal any significant feature in the family of kernel estimates. Our method allow us to establish a diagnostic regarding the validity of the SAINT model when describing mortality patterns in four different countries.

This study explored differences in student-athletes’ symptoms of depression, anxiety, and stress pre- to post-COVID-19 pandemic. The WHO reported a 25% increase in depression and anxiety rates worldwide with young people disproportionately affected. Student-athletes face many stressors related to their sporting and academic feats but what is not known is how the COVID-19 pandemic affected their experiences of mental illness. A multiple cohort cross-sectional study design was employed, and data collected using physical and online surveys. Participants (M age = 19.98 years, SD = 1.50) were recruited from UK universities (N = 807; 427 pre-pandemic cohort, 380 post-pandemic cohort). Results revealed statistically significant differences in mean depression, anxiety, and stress scores between cohorts. Scores for the post-pandemic cohort were significantly higher than pre-pandemic, suggesting a worsening of symptom severity. Distributions of student-athletes across categories of symptom severity also worsened for depressive and anxiety symptoms post-pandemic and were skewed towards more severe categories. Symptoms of de-pression, anxiety, and stress were a concern pre-pandemic. Rates are higher in the post-pandemic cohort, suggesting a worsening of symptoms. This data adds to evidence on student-athletes’ symptoms of mental illness by exploring a UK sample and comparing scores pre- and post-pandemic.

Pituitary adenylate cyclase-activating polypeptide receptor 1 (PAC1-R) has a higher affinity for pituitary adenylate cyclase- activating polypeptide (PACAP) than for vasoactive intestinal peptide (VIP). PACAP exerts its neuroprotective effects through PAC1-R. PAC1-R has become a target for drug development, and we targeted PAC1-R to screen small positive allosteric modulator 1 (SPAM1). SPAM1 has a neuroprotective effects, and in the D-galactose (D-gal) mouse model, SPAM1 improved the structure of the hippocampal dentate gyrus and restored the number of neurons. Compared with D-gal model mice, SPAM1 treatment upregulated the expression of Sirtuin 6 (SIRT6) and Lamin B1, and downregulated the expression of YinYang 1 (YY1) and p16. Consistent with this, the same results were obtained in senescent RGC-5 cells. Meanwhile, SPAM1 was also found to up-regulate SIRT6 and down-regulate YY1 expression in normal RGC-5 cells. Then, we further explored the mechanism of SPAM1 neuroprotection by whole transcriptome sequencing and proteomic analysis, and found that SPAM is involved in the longevity regulating pathway, and confirmed the up-regulation of neurofilament light polypeptide and neurofilament medium polypeptide by western blot, thus laying a pharmacological foundation for SPAM1 as a therapeutic agent for neurodegenerative diseases. polypeptide and neurofilament medium polypeptide. Thus, it lays a pharmacological foundation for SPAM1 as a therapeutic drug for neurodegenerative diseases.

In this paper, we first define the concepts of r-fuzzy soft α-open (semi-open and δ-open) sets on fuzzy soft topological spaces based on the article Aygunoglu et al. (Hacet. J. Math. Stat., 43 (2014), 193-208), and the relations of these sets with each other are established. In addition, we introduce the concepts of fuzzy soft δ-closure (δ-interior) operators, and study some properties of them. Also, the concept of r-fuzzy soft δ-connected sets is introduced and studied with help of fuzzy soft δ-closure operators. Thereafter, we define the concepts of fuzzy soft α-continuous (β-continuous, semi-continuous, pre-continuous and δ-continuous) functions, which are weaker forms of fuzzy soft continuity, and some properties of these functions along with their mutual relationships are discussed. Moreover, a decomposition of fuzzy soft α-continuity and a decomposition of fuzzy soft semi-continuity is obtained. Finally, as a weaker form of a fuzzy soft continuity, the concepts of fuzzy soft almost (weakly) continuous functions are defined, and some properties are specified. Additionally, we explore the notion of continuity in a very general setting called, fuzzy soft (L, M, N, O)-continuous functions and a historical justification is introduced.

Low-resource languages often face the problem of insufficient data, which leads to poor quality in machine translation. One approach to address this issue is data augmentation. Data augmentation involves creating new data by transforming existing data through methods such as flipping, cropping, rotating, and adding noise. Traditionally, pseudo-parallel corpora are generated by randomly replacing words in low-resource language machine translation. However, this method can introduce ambiguity as the same word may have different meanings in different contexts. This study proposes a new approach for low-resource language machine translation, which involves generating pseudo-parallel corpora by replacing phrases. The performance of this approach is compared with other data augmentation methods, and it is observed that combining it with other data augmentation methods further improves performance. To enhance the robustness of the model, R-Drop regularization is also used. R-Drop is an effective method for improving the quality of machine translation. The proposed method was tested on Chinese-Kazakh (Latin script) translation tasks, resulting in performance improvements of 4.99 and 7.7 for Chinese-to-Kazakh and Kazakh-to-Chinese translations, respectively.

Early detection of wildfires has been limited using the sun-synchronous orbit satellites due to their low temporal resolution and wildfires’ fast spread in the early stage. NOAA’s geostationary weather satellites GOES-R can acquire images every 15 minutes at 2km spatial resolution, and have been used for early fire detection. However, advanced processing algorithms are needed to provide timely and reliable detection of wildfires. In this research, a deep learning framework, based on Gated Recurrent Units (GRU), is proposed to detect wildfires at early stage using GOES-R dense time series data. GRU model maintains good performance on temporal modelling while keep a simple architecture, makes it suitable to efficiently process time-series data. 36 different wildfires in North and South America under the coverage of GOES-R satellites are selected to assess the effectiveness of the GRU method. The detection times based on GOES-R are compared with VIIRS active fire products at 375m resolution in NASA’s Fire Information for Resource Management System (FIRMS). The results show that GRU-based GOES-R detections of the wildfires are earlier than that of the VIIRS active fire products in most of the study areas. Also, results from proposed method offer more precise location on the active fire at early stage than GOES-R Active Fire Product in mid-latitude and low-latitude regions.

We present a methodology to enable users to interact with statistical information owned by an institution and stored in a cloud infrastructure. Mainly based on R, this approach was developed following the open-data philosophy. Also, since we use R, the implementation is mainly based on open-source software. R gives several advantages from the point of view of data management and acquisition, as it becomes a common framework that can be used to structure the processes involved in any statistical operation. This simplifies the access to the data and enable to use all the power of R in the cloud information. This methodology was applied successfully to develop a tool to manage the data of the Centre d’Estudis d’Opinió, but it can be applied to other institutions to enable open access to its data. The infrastructure also was deployed to a cloud infrastructure, to assure the scalability and a 24/7 access.

Background: In the heart, aldosterone (Aldo) binds the mineralocorticoid receptor (MR) to exert damaging, adverse remodeling-promoting effects. We recently showed that G protein-coupled receptor (GPCR)-kinase (GRK)-5 blocks the cardiac MR by directly phosphorylating it, thereby repressing its transcriptional activity. MR antagonist (MRA) drugs block the cardiac MR reducing morbidity and mortality of advanced human heart failure. Non-steroidal MRAs, such as finerenone, may provide better cardio-protection against Aldo than classic, steroidal MRAs, like spironolactone and eplerenone. Herein, we sought to investigate potential differences between finerenone and eplerenone at engaging GRK5-dependent cardiac MR phosphorylation and subsequent blockade. Methods: We used the cardiomyocyte cell line H9c2 and neonatal rat ventricular myocytes (NRVMs). Results: GRK5 phosphorylates the MR in H9c2 cardiomyocytes in response to finerenone but not to eplerenone. Unlike eplerenone, finerenone alone potently and efficiently suppresses cardiac MR transcriptional activity, thus displaying inverse agonism. GRK5 is necessary for finerenone`s inverse agonism, since GRK5 genetic deletion renders finerenone incapable of blocking cardiac MR transcriptional activity. Eplerenone alone does not fully suppress cardiac MR basal activity regardless of GRK5 expression levels. Finally in NRVMs, GRK5 is necessary for the anti-apoptotic and anti-fibrotic effects of both finerenone and eplerenone against Aldo, as well as for the higher efficacy and potency of finerenone at blocking Aldo-induced apoptosis and fibrosis. Conclusions: Finerenone, but not eplerenone, induces GRK5-dependent cardiac MR inhibition, which underlies, at least in part, its higher potency and efficacy, compared to eplerenone, as an MRA in the heart. GRK5 acts as a co-repressor of the cardiac MR and is essential for efficient MR antagonism in the myocardium.

We examined the amount of marbling and tested the genome of boars from 5 breeds of Duroc, Iberian, Lacombe, Berkshire and Pietrian that were commercially available for a swine herd in Canada. The marbling was ranked according to the amount of intramuscular fat % obtained in loin chops consisting of the longissimus dorsi muscle. The genetics were analysed by genome wide association study using 80,000 single nuclear polymorphism (SNP) microarrays. Our samples had pork that achieved > 7 % IMF from 110kg animals. Meta-analysis revealed SNP markers that were associated with the highest marbled pork chops on chromosomes 5, 7, and 16. Using the susScr 11.1 map, we determined that the nearest genes were SSNP, Rh glycoprotein and EGFLAM. We tested a sub-population of Duroc sired animals and found a different set of markers close to GRLB and KCNJ3 on chromosomes 8 and 15. Based on our sample, we can achieve pork with good marbling from animals conventionally raised to standard market weights of 110kg. The choice of a good marbling line of pig is not necessarily breed specific.

The oil and gas industry in Nigeria, a vital contributor to the nation's economy, has long been associated with significant environmental challenges. Pollution, habitat destruction, and greenhouse gas emissions have raised global concerns about sustainability and corporate responsibility. This empirical study explores the relationship between environmental accounting practices and the financial performance of listed oil and gas companies in Nigeria. We investigated eight oil and gas companies that are publicly traded on the Nigerian Stock Exchange Market (NGX) as of January 17, 2022, from 2011 to 2022. The study employs Driscoll-Kraay standard errors and reveals that environmental accounting had significant effects on returns on assets, earnings per share, and liquidity ratio. The study revealed that the implementation of environmental accounting practices had diverse effects on the performance of oil and gas companies in Nigeria. The findings encourage policymakers and stakeholders in the sector to utilise the insights and design more effective regulations and incentives that promote environmental corporate responsibility. Also, valuable insights into the potential benefits and challenges associated with adopting environmental accounting practices, and influencing the decision-making processes of corporate stakeholders were provided to ensure sustainability in terms of improved financial performance of the oil and gas sector in Nigeria.

The review scrutinizes the currently performed research on the new methods for enhancing bituminous binder performance through radiation and radical grafting of polymer modifers of bitumen. It investigates innovative methods, including using waste polymers as modifiers, and applying radiation for polymer grafting, to overcome challenges like high costs, low aging resistance and storage stability issues, of which separation of phases polymer/bitumen is the most significant obstacle. These advanced modification techniques promise sustainability through the decrease of the carbon footprint of transportation systems by improving the properties and durability of binders. Additionally, the review discusses the parameters and mechanistic aspects from a scientific perspective, shedding light on the underlying processes that contribute to the improved performance of modified bituminous binders.

It has been proven that in standard Einstein gravity, exotic matter (i.e. matter violating the point-wise and averaged weak and null energy conditions) is required to stabilize traversable wormholes. Quantum field theory permits these violations due to the quantum coherent effects found in any quantum field . Even reasonable classical scalar fields violate the energy conditions. In the case of the Casimir effect and squeezed vacuum states, these violations have been experimentally proven. It is advantageous to investigate methods of minimizing the use of exotic matter. One such area of interest is extended theories of Einstein gravity. It has been claimed that in some extended theories, stable traversable wormholes solutions can be found without the use of exotic matter. There are many extended theories of gravity and in this review paper we first explore f(R) theories and then explore some wormhole solutions in f(R) theories including Lovelock gravity.

We analyse recent contradictory results and conclusions about the spectrum of the screened Coulomb potential $V(r)=-r^{-1}e^{-C/r}$. The well known Hellmann-Feynman theorem shows that all the bound states of the Coulomb potential ($C=0$) remain bounded as $C$ increases. We derive a simple approximate analytical expression for the eigenvalues for sufficiently small values of the screening parameter $C$ and an approximate asymptotic expression for the asymptotic behaviour of the s-state eigenvalues when $C\rightarrow \infty $. Present results are expected to resolve the discrepancy about the spectrum of the quantum-mechanical model just mentioned.

A locally-rotationally-symmetric Bianchi-I model filled with strange quark matter (SQM) is explored in f(R, T) gravity. We take f(R, T) = R + 2 f(T) = R + 2λT, where R is the Ricci scalar, T is the trace of energy-momentum tensor and λ is an arbitrary constant. Exact solutions are obtained by assuming that the expansion scalar is proportional to the shear scalar. This yields a constant value for the deceleration parameter, q = 2, which corresponds to the decelerated phase of the universe. The model is found to be physically viable for λ < −1. SQM during early evolution mimics ultra-relativistic radiation whereas at late times, it behaves as dust, quintessence or even the cosmological constant depending on the value of λ. The effective matter acts as a stiff fluid irrespective of the matter content and of the f(R, T) terms. The model is shear free at late times but remains anisotropic throughout the evolution. In the absence of the f(R, T) terms, SQM accelerates the universe. In the specific case when SQM vanishes at late times, the effect of f(R, T) is to accelerate the universe. The model admits the possibility that SQM could be an alternative to dark energy.

Polyhedral oligomeric silsesquioxane (POSS) is a suitable nanoscale reinforcement for thermosetting polymers, such as epoxy resin systems in order to modify its mechanical, thermal, and chemical properties. The inclusion of POSS in the epoxy resin at higher loading (greater than 1 wt.%), however, introduces the ductility during the fracture behavior of these nanocomposites. Consequently, the J-integral is used to quantify the fracture behavior of these materials and characterize the crack growth resistance curve against stable crack growth. A range of nanocomposites is prepared by adding 0.5, 1, 3, 5, and 8 wt.% of glycidyl POSS into DGEBF epoxy resin cured with an amine-based curing agent. From the fracture toughness experiment the load-displacement result confirms that when the POSS reinforcement is greater than 1 wt.%, the fracture behavior of the nanocomposite changes from brittle to ductile. For both brittle and ductile nanocomposites, the addition of POSS molecules improves the crack initiation toughness. The development of POSS–POSS compliant domains are reported previously, is attributed for this change in the failure behavior. The fractured images of POSS–epoxy nanocomposites, obtained using scanning electron microscopy, show that the increase in fracture resistance at higher values of POSS loading occurs due to the extensive shear yielding. Meanwhile, the increased fracture toughness at lower values of POSS loading occurs due to crack pinning and crack deflection.

We obtain exact solutions to the field equations for 5 dimensional LRS Bianchi type-I spacetime in $f(R,T)$ theory of gravity where specifically the following three cases are considered: (i) $f(R,T)=\mu(R+T)$, (ii) $f(R,T)=R \mu + R T \mu^2$ and (iii) $f(R,T)=R+\mu R^2+\mu T$ where $R$ and $T$ respectively the Ricci scalar and trace of the energy-momentum tensor. It is found that the equation of state (EOS) parameter $w$ is governed by the parameter $\mu$ involved in the $f(R,T)$ expressions. We fine-tune the parameter $\mu$ to obtain effect of phantom energy in the model, however we also restrict this parameter to obtain a stable model of the universe. It is noted that the model isotropizes at finite cosmic time.

In this paper, we introduce a new generalization of the r-Stirling numbers of the second kind based on the q-numbers via an exponential generating function. We investigate their some properties and derive several relations among q-Bernoulli numbers and polynomials, and newly de…ned (q, r, w)-Stirling numbers of the second kind. We also obtain q-Bernstein polynomials as a linear combination of (q, r, w)-Stirling numbers of the second kind and q-Bernoulli polynomials in w.

Fowlpox virus (FPV) has been used as a vector for many years. To date, surprisingly, very little data exist on the persistence of fowlpox vaccines in chicken tissues, or what kind of immune cells respond to the vaccination at the site of inoculation. Although both humoral and cellular mediated immunity (CMI) play a part in overall immunity against FPV, little is known regarding the cell-mediated immune responses to FPV infection. The main aim of this paper was to measure persistence of the recombinant fowlpox vaccine in the skin tissues following vaccination. The results showed that the recombinant FPVs do not persist for long, and are cleared by 6 days post-vaccination (dpv). The response of immune cells (macrophages, B cells, CD4+ and CD8+ T cells) that infiltrating the site of vaccination was estimated.

Chamois are mountain ungulates (Subfamily Caprinae) which inhabit several medium and high altitude mountain ranges from southern Europe to the Near East. The first findings of Sarcocystis cysts in the musculature of chamois were reported in the 1970s. However, only limited work on the epidemiology of sarcocystosis and identification of the species of Sarcocystis in chamois has been done in the past. The present work was part of a comprehensive study on the parasites of chamois in Germany aiming to provide, for the first time, data on the prevalence and intensity of Sarcocystis infection in native Alpine chamois using histology examination of heart and/or diaphragm tissue samples collected from 216 chamois (40 kids and 176 chamois ranging of one up to 18 years of age). Sarcocysts were detected in either heart or diaphragm of 167/216 chamois (77.3%) with 131 of 183 heart samples and 127 of 215 diaphragm samples testing sarcocyst positive. Of the 181 chamois with both heart and diaphragm available (34 kids and animals up to 18 years of age), sarcocysts were detected in heart and/or diaphragm of 142 animals translating in an overall 78.5% prevalence of Sarcocystis infection (95%CI 72.5% - 84.4%). Sarcocysts were more frequently recorded in heart vs. diaphragm (72.4% vs. 56.4%; p=0.0021), and diaphragm positivity was associated with heart positivity (p=0.0001). Sarcocyst positivity (heart and/or diaphragm) was significantly (p<0.001) lower in kids than in the older chamois (27.1% vs. 88.6%, respectively) but prevalence did not differ between the sexes, regardless of the chamois’ age (p>0.3). Intensity of infection was generally low (<10 sarcocysts per cm² muscle cut) in both heart positive and diaphragm positive animals (94.7% and 93.7%, respectively) with heart yielding higher sarcocyst counts than diaphragm (p<0.001). Both heart and diaphragm sarcocyst counts were significantly (p<0.001) lower in kids than in the older chamois. Sarcocystis infection was demonstrated to be prevalent in chamois in Germany but intensity is apparently low. Further studies are desired to identify the species of Sarcocystis parasitizing the chamois using both phenotypic and molecular characteristics.

The vast array of interconnected microbes across earth’s ecosystems and within holobionts has been called the “Internet of Microbes.” Research into the fundamental microbial properties has demonstrated that bacteria and archaea are masters of energy and information collection, storage, transformation, and dissemination using both “wired” and wireless (at a distance) capacities. These features suggest that microbes are quantum entangled within and between earth’s holobionts, and that specific tools affecting energy and information functions could provide an effective strategy for managing microbial populations. Microbes use four critically important microbial networking functions (sound, light, electricity, and magnetism). This narrative review focuses on microbial management based on two of the four: sound and light (as well as related vibrations). These are examined as: 1) tools for managing microbial populations, 2) tools to support new technologies, and 3) tools for healing humans and other holobionts. Given microbial sensitivity to sound, light, and vibrations, it is critical that microbial populations and microbe-laden holobionts are protected from potentially damaging exposures. We conclude that sound, light, and vibrations are useful therapeutic tools that can help support useful microbial populations and help to address ongoing challenges of holobiont disease.

Chronic Kidney Disease (CKD) and Cardiovascular Disease (CVD) are two devastating diseases that may occur in non-diabetics or individuals with diabetes and when combined is referred to as cardiorenal disease. The impact of cardiorenal disease on society, the economy and the healthcare system is enormous. Although there are numerous therapies for cardiorenal disease, one therapy showing a great deal of promise is sodium-dependent glucose cotransporter 2 (SGLT2) inhibitors. The SGLT family member, SGLT2, is often implicated in the pathogenesis of a range of diseases and dysregulation of the activity of SGLT2 markedly effects the transport of glucose and sodium across the luminal membrane of renal cells. Inhibitors of SGLT2 were developed based on the anti-diabetic action initiated by inhibiting renal glucose reabsorption, thereby increasing glucosuria. Of great medical significance, large-scale clinical trials utilising a range of SGLT2 inhibitors have demonstrated both metabolic and biochemical benefits via numerous novel mechanisms such as sympathoinhibition which will be discussed in this review. In summary, SGLT2 inhibitors clearly exert cardio-renal protection in diabetic and non-diabetic subjects in both pre-clinical and clinical settings by improving hyperglycemia, high blood pressure, hyperlipidemia and diabetic retinopathy. (188 Words)

Quaking aspen (Populus tremuloides Michx.) is an important deciduous species in western U.S. forests. Existing maps of aspen distribution are based on Landsat imagery and often miss small stands (&lt;0.09 ha or 30 m²), which rapidly regrow when managed or following disturbance. In this study, we present methods for deriving a new regional map of aspen forests using one year of Sentinel-1 (S1) and Sentinel-2 (S2) imagery in Google Earth Engine. We assessed the annual phenology of aspen in the Southern Rockies and leveraged the frequent temporal resolution of S1 and S2 to create ecologically relevant seasonal composites. Additionally, we derived spectral indices and radar textural features targeting the canopy structure, moisture, and chlorophyll content. Using spatial block cross-validation and Random Forests, we assessed the accuracy of different scenarios and selected the best performing set of features for classification. Comparisons were then made with existing landcover products across the study region. The resulting map improves on existing landcover products in both accuracy (average F1-score = 93.1%) and detection of smaller forest patches. These methods enable accurate mapping at spatial and temporal scales relevant to forest management for one of the most widely distributed tree species in North America.

Due to the continuing high suicide rates among young men, there is a need to understand help-seeking behaviour and engagement with tailored suicide prevention interventions. The aim of this study was to compare help-seeking among younger and older men who attended a therapeutic centre for men in a suicidal crisis. In this case series study, data were collected from 546 men who were referred into a community-based therapeutic service in North West England. Of the 546 men, 337 (52%) received therapy; 161 (48%) were aged between 18 and 30 years (mean age 24 years, SD=3.4). Analyses included baseline differences, symptom trajectories for the CORE-34 Clinical Outcome Measure (CORE-OM) and engagement with the therapy. For the CORE-OM there was a clinically significant reduction in mean scores between assessment and discharge (p<0.001) for both younger and older men. At initial assessment, younger men were less affected by entrapment (46% v 62%; p=.02), defeat (33% v 52%; p=.01), not engaging in new goals (38% v 47%; p=.02), and positive attitudes towards suicide (14% v 18%; p=.001) than older men. At discharge assessment, older men were significantly more likely to have an absence of positive future thinking (15% v 8%; p=0.03), have less social support (45% v 33%; p=.02) and feelings of entrapment (17% v 14%; p=.02) than younger men. Future research needs to assess the long-term effects of help-seeking using a brief psychological intervention for young men in order to understand whether the effects of the therapy are sustainable over a period of time following discharge from the service.

Recently, a significant number of tools for detecting dangerous objects have been developed. Unfortunately, the performance offered by them is overestimated due to the poor quality of the datasets used (insufficiently numerous, contain items not strictly related to dangerous objects, insufficient range of presentation conditions). To fill in a gap in this area we have built an extensive dataset dedicated to detecting the objects most often used in various acts of breaching public security (baseball bat, gun, knife, machete, rifle). This collection contains images presenting the detected objects with different quality and under different environmental conditions. We believe that the results obtained from it are more reliable and give a better idea of the detection accuracy that can be achieved under real conditions. We used the Faster R-CNN with different backbone networks in the study. The best results were obtained for the ResNet152 backbone. The mAP value was 85%, while the AP level ranged from 80% to 91%, depending on the item detected. An average real-time detection speed was 11-13 FPS. Both the accuracy and speed of the Faster R-CNN model allow it to be recommended for use in public security monitoring systems aimed at detecting potentially dangerous objects.

The article explores Qualitative Comparative Analysis (QCA), an approach for establishing causal relationships between conditions and outcomes. QCA, applied in case studies and empirical analyses, facilitates generalizations for future research and addresses causal complexity by identifying various causal "recipes" leading to the same outcome. Three widely used QCA variants are Crisp-Set QCA (csQCA), Multi-value QCA (mvQCA), and Fuzzy-Set QCA (fsQCA), each with unique approaches. The article emphasizes the significance of bibliometric analysis in mapping a research field's intellectual structure, revealing key contributions and trends. In QCA, bibliometric analysis identifies leading researchers, affiliations, and influential countries. Results show QCA's widespread adoption across disciplines, with continuous growth in article production since 2013. The favored variant is fsQCA, followed by csQCA, and China notably contributes to QCA-related research. In conclusion, QCA proves a potent tool for discerning complex causal relationships in empirical studies, with its increasing interdisciplinary use indicating substantial potential for advancing scientific knowledge.

This paper introduces the spatial component in cross-section econometric estimations and specifically, the spatial dependence effect inherent in some of the variables involved in the modelling process. First, the spatial structure of the data from thematic maps is observed and Moran's spatial autocorrelation indicators are presented. Subsequently, the spatial weights matrix is built under different specifications. Finally, several modelling specification strategies are shown and the interpretation of the estimated coefficients. The theoretical concepts are illustrated with examples and their corresponding R software codes. This code and databases are available in a freely accessible repository in the BE2SHARE-EUDAT platform so that they can be easily reproduced.

This paper introduces an application of R programming language for geostatistical data processing with a case study of the Mariana Trench, Pacific Ocean. The formation of the Mariana Trench, the deepest among all hadal oceanic depth trenches, is caused by complex and diverse geomorphic factors affecting its development. Mariana Trench crosses four tectonic plates: Mariana, Caroline, Pacific and Philippine. The impact of the geographic location and geological factors on its geomorphology has been studied by methods of statistical analysis and data visualization using R libraries. The methodology includes following steps. Firstly, vector thematic data were processed in QGIS: tectonics, bathymetry, geomorphology and geology. Secondly, 25 cross-section profiles were drawn across the trench. The length of each profile is 1000-km. The attribute information has been derived from each profile and stored in a table containing coordinates, depths and thematic information. Finally, this table was processed by methods of the statistical analysis on R. The programming codes and graphical results are presented. The results include geospatial comparative analysis and estimated effects of the data distribution by tectonic plates: slope angle, igneous volcanic areas and depths. The innovativeness of this paper consists in a cross-disciplinary approach combining GIS, statistical analysis and R programming.

Radar altimetry provides valuable measurements to characterize the state and the evolution of the Antartica and Greenland ice sheet cover. Global Navigation Satellite System Reflectometry (GNSS-R) has the potential capacity of complementing the dedicated radar altimeters incrementing the temporal and spatial resolution of the surface height measurements. In this work we perform an study of the Greenland ice sheet using data obtained by the GNSS-R instrument aboard the British TechDemoSat-1 (TDS-1) satellite mission, designed primarily to provide sea state information, like sea surface roughness or wind, but not altimetric products. The data has been analyzed with altimetric methodologies, already proved in aircraft based experiments, to extract signal delay observables to be used to infer the topography of the Greenland cover. The penetration depth of the GNSS signals into ice has also considered. The topographic signal obtained is consistent with those obtained with other passive or active microwave sensors. The main conclusion derived from this work is that GNSS-R also provides valuable measurements of the ice sheet cover and, as taken at a variety of geometries and at least two frequency bands, they prospect different depths into the ice. They have thus potential to complement our understanding of the ice firn and its evolution.

The Philippines is both a biodiversity hotspot and a megadiverse country. The country also has experienced one of the highest rates of deforestation in Southeast Asia and is among the first countries to introduce a massive reforestation program to address the country’s rapid biodiversity and forest loss. Drawing upon an empirical study from the Leyte island and other relevant case studies from the Philippines, in this chapter, we demonstrate that recovering secondary forests following shifting cultivation, locally known as kaingin have the high potentials for biodiversity and carbon co-benefits. Based on our empirical study, we also found that secondary forest regrowing after kaingin use can potentially be used as a cost-effective reforestation measure with multiple benefits to people and the environment in upland areas of the Philippines. We also discuss measures that are essential for such programs to be successful.

The goal of newborn screening is to improve health outcomes by identifying and treating affected newborns. This manuscript provides an overview of a data tool to facilitate the longitudinal collection of health information on newborns diagnosed with a condition through NBS. The Newborn Screening Translational Research Network (NBSTRN) developed the Longitudinal Pediatric Data Resource (LPDR) to capture, store, analyze, visualize, and share genomic and phenotypic data over the lifespan of NBS identified newborns to facilitate understanding of genetic disease, and to assess the impact of early identification and treatment. NBSTRN developed a consensus-based process using clinical care experts to create, maintain, and evolve question and answer sets organized into common data elements (CDEs). The LPDR contains 24,172 core and disease-specific CDEs for 118 rare genetic diseases, and the CDEs are being made available through the NIH CDE Repository. The number of CDEs for each condition average of 2,200 with a range from 69 to 7,944. The LPDR is used by state NBS programs, clinical researchers, and community-based organizations. Case level, de-identified data sets are available for secondary research and data mining. The development of the LPDR for longitudinal data gathering, sharing, and analysis supports research and facilitates the translation of new discoveries into clinical practice.

In the recent decades, per- and polyfluoroalkyl substances (PFAS) have garnered widespread public attention due to their persistence in the environment and detrimental effects on the health of living organisms, spurring the generation of several transcriptome-centered investigations to understand the biological basis of their mechanism. In this study, we collected 2144 publicly available samples from 7 distinct animal species to examine the molecular responses to PFAS exposure and to determine if there are conserved responses. Our comparative transcriptional analysis revealed that exposure to PFAS is conserved across different tissues, molecules and species. We identified and reported several genes exhibiting consistent and evolutionarily conserved transcriptional response to PFAS, such as ESR1, HADHA and ID1, as well as several pathways including lipid metabolism, immune response and hormone pathways. This study provides the first evidence that distinct PFAS molecules induce comparable transcriptional changes and affect the same metabolic processes across inter-species borders. Our findings have significant implications for understanding the impact of PFAS exposure on living organisms and the environment. We believe that this study offers a novel perspective on the molecular responses to PFAS exposure and provides a foundation for future research into developing strategies for mitigating the detrimental effects of these substances in the ecosystem.

Health and social needs exist along a dynamic continuum. Recognizing that health status is inextricably impacted by social determinants of health, community paramedicine has opportunities and a responsibility to reduce inequities. The objective of this scoping review was to investigate peer-reviewed and grey literature to explore how community paramedicine supports community needs along a health and social continuum. We conducted a scoping review of English language literature using the JBI Scoping Review methodology. We searched CINAHL, EMBASE, MEDLINE, Google Scholar, and organisational websites. 30 peer-reviewed and 13 grey literature articles met inclusion criteria. The findings describe the ways community paramedicine models evolved from minimising system pressures on emergency health services to addressing health and social needs. A key recommendation across the literature was the need to meaningfully engage communities early in program development to understand how best to implement and co-design integrated service models addressing specific community needs, though there was a lack of evidence to guide this approach. There is a notable lack of evidence pertaining to optimising technologies in program design and implementation. Results highlight opportunities to determine best practices for conducting holistic community needs assessments that include equitable stakeholder engagement and enhancing education to prepare paramedics for expanded roles. Community paramedicine provides opportunities to better meet the needs of structurally marginalised communities. There is a social responsibility and opportunity to engage communities to co-design service delivery, advance paramedic education, and enhance interprofessional collaboration to better support community needs and generate upstream solutions for individuals and communities.

RNA interference (RNAi) using small interfering RNAs (siRNAs) is a powerful tool to target any protein of interest and is becoming more implementable for in vivo applications due to recent developments in RNA delivery systems. To exploit RNAi for cancer treatment, it is expedient to increase its selectivity by e.g. a prodrug approach to activate the siRNAs upon external triggering, e.g. by using light. Red light is especially well suitable for in vivo applications due to its low toxicity and higher tissue penetration. Known molecular (not nanoparticle based) red light activatable siRNA prodrugs rely on singlet oxygen (1O2) mediated chemistry. 1O2 is highly cytotoxic. Additionally one of the side products in the activation of the known siRNA prodrugs is anthraquinone, which is also toxic. We here report on an improved red light activatable siRNA prodrug, which do not require 1O2 for their activation. The 5’ terminus of its antisense strand is protected with an electron-rich azobenzene promoiety. It gets reduced and cleaved upon red light exposure in the presence of Sn(IV)(pyropheophorbide a)dichloride acting as a catalyst and ascorbate required as a bulk reducing agent producing active siRNAs.

Predator-prey interactions present heightened opportunities for pathogen spillover, as predators are exposed to novel parasites through consumption of prey harboring potentially infectious agents. Epizootics with high morbidity and mortality have been recorded following prey-to-predator spillover events with significant conservation implications, particularly for sensitive species. However, relatively few virulent infections following prey consumption are reported, given the very large number of exposures that presumably occur. Further, many transmitted agents are infectious but clinically silent and thus go unrecognized. Mechanisms that determine outcome of predator exposure to prey-based pathogens therefore represent an important, understudied component of disease dynamics that should be considered in modeling approaches and empirical research to better understand disease risk and emergence, particularly in vulnerable or threatened species.