Immune checkpoint inhibitors (ICIs) have revolutionized cancer care and shown remarkable efficacy clinically. This efficacy is, however, limited to subsets of patients with significant infiltration of lymphocytes into the tumor microenvironment. To extend their efficacy to patients who fail to respond or achieve durable responses, it is now becoming evident that complex combinations of immunomodulatory agents may be required to extend efficacy to patients with immunologically “cold” tumours. Oncolytic viruses (OVs) have the capacity to selectively replicate within and kill tumour cells resulting in the induction of immunogenic cell death and the augmentation of anti-tumour immunity and have emerged as a promising modality for combination therapy to overcome the limitations seen with ICIs. Pre-clinical and clinical data has demonstrated that OVs can increase immune cell infiltration into the tumour and induce anti-tumour immunity, thus changing a “cold” tumour microenvironment that is commonly associated with poor response to ICIs, to a “hot” microenvironment which can render patients more susceptible to ICIs. Here, we review the major viral vector platforms used in OV clinical trials, their success when used as a monotherapy and when combined with adjuvant ICIs, as well as pre-clinical studies looking at the effectiveness of encoding OVs to deliver ICIs locally to the tumour microenvironment through transgene expression.

Analysis of the hourly Canadian Prairie data for the past 60 years has transformed our quantitative understanding of land-atmosphere-cloud coupling. The key reason is that trained observers made hourly estimates of opaque cloud fraction that obscures the sun, moon or stars, following the same protocol for 60 years at all stations. These 24 daily estimates of opaque cloud data are of sufficient quality that they can be calibrated against Baseline Surface Radiation Network data to give the climatology of the daily short-wave, longwave and total cloud forcing (SWCF, LWCF and CF). This key radiative forcing has not been available previously for climate datasets. Net cloud radiative forcing reverses sign from negative in the warm season to positive in the cold season, when reflective snow reduces the negative SWCF below the positive LWCF. This in turn leads to a large climate discontinuity with snow cover, with a systematic cooling of 10°C or more with snow cover. In addition, snow cover transforms the coupling between cloud cover and the diurnal range of temperature. In the warm season, maximum temperature increases with decreasing cloud, while minimum temperature barely changes; while in the cold season with snow cover, maximum temperature decreases with decreasing cloud and minimum temperature decreases even more. In the warm season, the diurnal ranges of temperature, relative humidity, equivalent potential temperature and the pressure height of the lifting condensation level are all tightly coupled to opaque cloud cover. Given over 600 station-years of hourly data, we are able to extract, perhaps for the first time, the coupling between cloud forcing and the warm season imbalance of the diurnal cycle; which changes monotonically from a warming and drying under clear skies to a cooling and moistening under cloudy skies with precipitation. Because we have the daily cloud radiative forci, which is large, we are able to show that the memory of water storage anomalies, from precipitation and the snowpack, goes back many months. The spring climatology shows the memory of snowfall back through the entire winter, and the memory in summer goes back to the months of snowmelt. Lagged precipitation anomalies modify the thermodynamic coupling of the diurnal cycle to the cloud forcing, and shift the diurnal cycle of mixing ratio which has a double peak. The seasonal extraction of the surface total water storage is a large damping of the interannual variability of precipitation anomalies in the growing season. The large land-use change from summer fallow to intensive cropping, which peaked in the early 1990s, has led to a coupled climate response that has cooled and moistened the growing season, lowering cloud-base, increasing equivalent potential temperature, and increasing precipitation. We show a simplified energy balance of the Prairies during the growing season and its dependence on reflective cloud.

Pathogenic adenovirus (Ad) infections are widespread but typically mild and transient, except in the immunocompromised. As vectors for gene therapy, vaccine and oncology applications, Ad based platforms offer advantages including ease of genetic manipulation, scale of production and well established safety profiles, making them attractive tools for therapeutic development. However, the immune system often poses a significant challenge that may need to be overcome for adenovirus based therapies to be truly efficacious. Both pre-existing anti-Ad immunity in the population as well as the rapid development of an immune response against engineered adenoviral vectors can have detrimental effects upon the downstream impact of an adenovirus-based therapeutic. This review focusses on the different challenges posed, including pre-existing natural immunity and anti-vector immunity induced by a therapeutic, both in context of the innate and adaptive immune responses. We summarize different approaches developed with the aim of tackling these problems, as well as their outcomes and potential future applications.

The first diastereoselective synthesis of (–)-1-epi-lentiginosine stars from a common chiral trans-epoxyamide derived from 2-pyridincarbaldehyde is reported. This methodology involves a sequential oxirane ring opening and intramolecular 5-exo-tet cyclization of tosylate tras-epoxyalcohol to afford a diastereomeric mixture of indolizinium salts in a one-pot fashion, followed by regio- and diastereospecific pyridinium ring reduction.

More people are surviving longer with cancer. Whilst this can be partially attributed to advances in early detection of cancers, there is little doubt that the improvement in survival statistics is also due to the expansion in the spectrum of treatments available for efficacious treatment. Transformative amongst those are immunotherapies, which have proven effective agents for treating immunogenic forms of cancer, though immunologically “cold” tumour types remain refractive. Oncolytic viruses, such as those based on adenovirus have great potential as anti-cancer agents and have seen a resurgence of interest in recent years. Amongst their many advantages is their ability to induce immunogenic cell death (ICD) of infected tumour cells, thus providing the alluring potential to synergize with immunotherapies by turning immunologically “cold” tumours “hot”. Additionally, enhanced immune mediated cell killing can be promoted through the local overexpression of immunological transgenes, encoded from within the engineered viral genome. To achieve this full potential requires the development of refined, tumour selective “precision virotherapies” that are extensively engineered to prevent off-target up take via native routes of infection, and targeted to infect and replicate uniquely within malignantly transformed cells. Here, we review the latest advances towards this holy grail within the adenoviral field.

Background: As part of the Heart Healthy Lenoir Project, we developed a practice level intervention to improve blood pressure control. The goal of this study was: i) determine if single nucleotide polymorphisms (SNPs) that associate with blood pressure variation, identified in large case-control studies, are applicable to blood pressure control in subjects from a rural population; ii) measure the association of these SNPs with subjects’ responsiveness to the hypertension intervention; and iii) identify other SNPs that may help understand patient-specific responses to an intervention. Methods and Results: We used a combination of candidate SNPs and genome-wide analyses to test associations with either baseline systolic blood pressure (SBP) or change in systolic blood pressure one year after the intervention in two genetically defined ancestral groups: African Americans (AA) or Caucasian Americans (CAU). Of the 48 candidate SNPs, 13 SNPs associated with baseline SBP in our study; however, one candidate SNP, rs592582, also associated with a change in SBP after one year. Using our study data, we identified 4 and 15 additional loci that associated with a change in SBP in the AA and CAU groups, respectively. Our analysis of gene-age interactions identified genotypes associated with SBP improvement within different age groups of our populations. Moreover, our integrative analysis identified AQP4-AS1 and PADI2 as genes whose expression levels may contribute to the pleiotropy of complex traits involved in cardiovascular health and blood pressure regulation in response to an intervention targeting hypertension. Conclusions: Identification of SNPs associated with the success of a hypertension treatment intervention suggests that genetic factors in combination with age may contribute to an individual’s success in lowering SBP. If these findings prove to be applicable to other populations, the use of this genetic variation in making patient-specific interventions may help providers with making decisions to improve patient outcomes. Further investigation is required to determine the role of this genetic variance with respect to the management of hypertension such that more precise treatment recommendations may be made in the future as part of personalized medicine.

The licensing of talimogene laherparepvec (T-Vec) represented a landmark moment for oncolytic virotherapy, since it provided unequivocal evidence for the long-touted potential of genetically modified replicating viruses as anti-cancer agents. Whilst T-Vec is promising as a locally delivered virotherapy, especially in combination with immune-checkpoint inhibitors, the quest continues for a virus capable of specific tumour cell killing via systemic administration. One candidate is oncolytic adenovirus (Ad); it’s double stranded DNA genome is easily manipulated and a wide range of strategies and technologies have been employed to empower the vector with improved pharmacokinetics and tumour targeting ability. As well characterised clinical and experimental agents, we have detailed knowledge of adenoviruses’ mechanisms of pathogenicity, supported by detailed virological studies and in vivo interactions. In this review we highlight the strides made in the engineering of bespoke adenoviral vectors to specifically infect, replicate within, and destroy tumour cells. We discuss how mutations in genes regulating adenoviral replication after cell entry can be used to restrict replication to the tumour, and summarise how detailed knowledge of viral capsid interactions enable rational modification to eliminate native tropisms, and simultaneously promote active uptake by cancerous tissues. We argue that these designer-viruses, exploiting the viruses natural mechanisms and regulated at every level of replication, represent the ideal platforms for local overexpression of therapeutic transgenes such as immunomodulatory agents. Where T-Vec has paved the way, Ad-based vectors now follow. The era of designer oncolytic virotherapies looks decidedly as though it will soon become a reality.

In this study, 10%PTFE/PEEK blend were modified by potassium titanate whisker (PTW) and chopped glass fiber (GF), respectively. The blends were prepared by three-screw extruder. Through the investigation of thermal stability, tribological properties, mechanical properties and rheological behavior, the effects of reinforcing agents were determined. The results illustrated that the mechanical properties of 10%PTFE/PEEK blend can be dramatically improved by adding reinforcing agent of PTW or GF, and the reinforcing effect of GF was especially obvious. As for tribological properties, 1% addition was the best proportion. The friction coefficient and wear rate of the blend with 1% PTW were 0.283 and 4.97 × 10^-6 mm³/N · m, which decreased by 7.2% and 21% compared with those of the blend without reinforcing agent.

In eastern part of Ethiopia groundnut is very commonly intercropped with sorghum. Even though intercropping of sorghum with groundnut is practiced in the eastern part of Ethiopia the population density at what ratio should not be known. Therefore determining the population ratio is found to be crucial to draw management options. The study was conducted at two locations at Fadis (on station) and Babile (sub- station). Sorghum variety (Teshale) and groundnut (Fetene) were used as planting materials. All agronomic data were collected and analyzed by using GenStat software. Significant different were obtained among the treatments. The research result showed that, there were significance difference for both sorghum and ground nut yield per hectare in the years (2014 and 2015) among treatments. The result over time(in 2014 and 2015) at Fadis and Erer showed that the highest sorghum and groundnut yield per hectare were obtained/harvested from the intra row spacing of 25cmx20cm and 30cmx20cm intercropping sorghum with ground nut system with (1.27 and 1.31) respectively. The highest LER (1.31) and highest GMV (10218.00 ETBr/ha) were obtained from the intercropping of 30cmx20cm (Sorghum & groundnut). Clearly showed that, with intercropping of sorghum and Groundnut, it is possible to produce additional yield of sorghum without significant reduction in groundnut yield. As a result of this, the intra spacing of the main crop (sorghum) 25cm and 30cm and for the subsidiary crop (groundnut) 20cm was recommended for further production in the study areas of eastern Harerghe zone and similar agro-ecologies.

That birds are maniraptoran theropod dinosaurs is now considered an evolutionary consensus. An “open” (i.e., completely, or substantially perforate) acetabulum is considered an important synapomorphy verifying the bird-dinosaur nexus. Here I present anatomical evidence from morphological aspects of the acetabulum and its important appurtenances, the supracetabular crest and the antitrochanter, that the hip anatomy differs substantially between dinosaurs and birds and for the current hypothesis of origins to be correct unlikely anatomical reversals would have been required. Given the thin bone of the acetabular walls and the varied tissue, both hard and soft, in the acetabular region and especially the lower part of the basin, it is apparent that many avian skeletons exhibit some anatomical loss of soft tissue and thin bone, some perhaps related to changes in gait, but also in part related to the dramatic trend in bone reduction associated with flight, especially in more advanced crown taxa. Many basal birds and early diverging neornithines tend to have a nearly closed or various levels of partially closed acetabula, thus rendering the current terms “open” or “closed” acetabula inaccurate; they should be modified or replaced.

This article traces the origination, distribution, kinematics, function, and nature of alternative lateral horse gaits, i.e. intermediate speed lateral-sequence gaits involving the synchronization of ipsilateral limbs in the swing phase. Such alternative lateral horse gaits (namely, the running walk, rack, broken pace, hard pace, and broken trot) have been prized by equestrians for their comfort, and have been found in select horse breeds for hundreds of years and even exhibited in fossil equid trackways. After exploring the evolution and development of alternative lateral gaits via fossil equid trackways, human art and historical writings, and the genetics and history of modern horse breeds, functional and biomechanical reasons are offered for the genesis of these gaits. The article concludes by tracing similarities and differences between and within the expression of these alternative lateral gaits by various horse breeds. Fast and low-swinging hard pacing gaits are common in several horse breeds of East and North Asia, high-stepping rack and running walk gaits are often displayed in European and North and South American breeds, the broken pace is found in breeds of Central Asia, Southeast Asia, West Asia, Western North America, and Brazil in South American, and the broken trot occurs in breeds of North Asia, South Asia, and the Southern United States, and Brazil South America.

Consumption of coffee by women early in their pregnancy has been viewed as potentially increasing the risk of miscarriage, low birth weight, and childhood leukemias. Many of these reports of epidemiologic studies have not acknowledged the potential biases inherent in studying the relationship between early-pregnancy-coffee consumption and subsequent events. I discuss five of these biases, recall bias, misclassification, residual confounding, reverse causation, and publication bias. Each might account for claims that attribute adversities to early-pregnancy-coffee consumption. To what extent these biases can be avoided remains to be determined. At a minimum, they need to be acknowledged wherever they might account for what is reported.

This study focuses on the potential medicinal properties of Campsis radicans L. extracts and its aim is to investigate the antioxidant and antiproliferative effects of these extracts on the human colon adenocarcinoma cell line (HT-29). Cytotoxic activity in the HT-29 cell line was evaluated, and the 3-dimensional structures of phenolic compounds were obtained using the GC-MS method. Docking simulations were performed with AutoDock Vina, targeting proteins that are crucial in the apoptotic pathway (Bax, Bcl-2, and Caspase-3). Drug similarities and ADMET estimates of the phenolic compounds were obtained from databases. The highest antioxidant activity of Campsis radicans L. plant was observed in ethanol and water extracts, with notable inhibition capacities. While the total phenolic content was highest in ethanol, water, and ether extracts respectively the total flavonoid content was highest in ethanol, then ether, and water extracts. Certain elements were undetectable in mineral determination, and others exceeded the toxic doses for plants. The water extract exhibited dose-dependent cytotoxic activity in the HT-29 cell line, with an IC50 value of 4.47 mg/mL. Molecular docking results revealed the binding of phenolic molecules to the active sites of apoptotic pathway proteins. The findings suggest that Campsis radicans L. plant possesses cytotoxic properties, significant phenolic and flavonoid content, and a high antioxidant capacity. These properties make it a potential candidate for treatment use, emphasizing its potential therapeutic value in the HT-29 cell line. Further research and exploration on the identified phenolic compounds could contribute to the development of novel therapeutic agents.

The large areas being targeted for tropical forest restoration as part of the UN Decade on Ecosystem Restoration will have major consequences for the flow of water through landscapes. Whilst the prevailing mantra that ‘more forest implies less streamflow’ remains true in terms of annual water yields, we demonstrate that opportunities for increased tree cover to improve seasonal flow regimes of streams, particularly baseflows, are important. We discuss several potential positive feedbacks of forest restoration on hydrological processes at various scales, including ‘trade-offs’ between changes in vegetation water use and infiltration after foresting degraded land; the recovery of the capacity of vegetation to capture ‘occult’ precipitation in specific coastal and montane settings; and enhanced moisture recycling and transport at various scales. Modelled changes in baseflow after foresting all degraded land climatically capable of carrying forest in the tropics suggested a positive effect in 10% of the land. For an additional 8%, the effect was predicted to be about neutral (<2 mm/y). We conclude that a more positive narrative regarding the relationship between tropical forestation and water availability is justified. It is time for greater involvement of hydrologists and atmospheric scientists in the development and assessment of forest landscape restoration efforts.

A multiscale modeling concept for numerical simulation of multiphysics turbulent flow utilizing map-based advection is described. The approach is outlined with emphasis on its theoretical foundations and physical interpretations in order to establish the context for subsequent presentation of the associated numerical algorithms and the results of validation studies. The model formulation is a synthesis of existing methods, modified and extended in order to obtain a qualitatively new capability. The salient feature of the approach is that time advancement of the flow is fully resolved both spatially and temporally, albeit with modeled advancement processes restricted to one spatial dimension. This one-dimensional advancement is the basis of a bottom-up modeling approach in which three-dimensional space is discretized into under-resolved mesh cells, each of which contains an instantiation of the modeled one-dimensional advancement. Filtering is done only to provide inputs to a pressure correction that enforces continuity and to obtain mesh-scale-filtered outputs if desired. The one-dimensional advancement, the pressure correction, and coupling of one-dimensional instantiations using a Lagrangian implementation of mesh-resolved volume fluxes is sufficient to advance the three-dimensional flow without time advancing coarse-grained equations, a feature that motivates the designation of the approach as autonomous microscale evolution (AME). In this sense, the one-dimensional treatment is not a closure because there are no unclosed terms to evaluate. However, the approach is additionally suitable for use as a subgrid-scale closure of existing large-eddy-simulation methods. The potential capabilities and limitations of both of these implementations of the approach are assessed conceptually and with reference to demonstrated capabilities of related methods.

Bimetallic nanoparticles are of interest since they lead to many interesting electrical, chemical, catalytic, and optical properties. They are particularly important in the field of catalysis since they show superior catalytic properties than their monometallic counterparts. The structures of bimetallic nanoparticles depend mainly on the synthesis conditions and the miscibility of the two components. In this work, PdPt alloyed-bimetallic nanoparticles (NPs) were synthesized through the polyol method, and characterized using spherical aberration (Cs) corrected scanning transmission electron microscopy (STEM). High-angle annular dark-field (HAADF)-STEM images of bimetallic nanoparticles were obtained. The contrast of images shows that nanoparticles have an alloy structure with an average size of 8.2 nm. Together with the characterization of nanoparticles, a systematic molecular dynamics simulations study, focused on the structural stability and atomic surface segregation trends in 923-atom PdPt alloyed-bimetallic NPs was carried out.

Pigmented corn is a gramineae food of great biological, cultural and nutritional importance for many Latin American countries, with more than 250 breeds in the American continent. It confers a large number of health benefits due to its diverse and abundant bioactive compounds. In this narrative review we decided to organize the information on the nutrients, bioactive compounds and phytochemicals present in pigmented corn, as well as their effects on human health. Phenolic compounds and anthocyanins are some of the most studied and representative compounds in these grasses, with a wide range of health properties, mainly the reduction of prooxidant molecules. Carotenoids are a group of molecules belonging to the terpenic compounds, present in a large number of pigmented corn breeds, mainly the yellow ones, whose biological activity incorporates a wide spectrum. Bioactive peptides can be found in abundance in corn, having very diverse biological effects that include analgesic, opioid, antihypertensive, etc. activity. Other compounds with biological activity found in pigmented corn are resistant starches, some fatty acids, phytosterols, policosanols, phospholipids, ferulic acid and phlobaphenes, as well as a great variety of vitamins, elements, and fibers. This review aims to disseminate and integrate the existing knowledge on compounds with biological activity in pigmented corn, in order to promote their research, interest and use by scientists, nutrition professionals, physicians, industries and the general population.

Glioblastoma (GBM) is the most common and aggressive adult brain cancer with an average survival rate of around 15 months in patients receiving standard treatment. Oncolytic adenovirus expressing therapeutic transgenes represent a promising alternative treatment for GBM. Of the many human adenoviral serotypes described to date, adenovirus 5 (Ad5) has been most utilized clinically and experimentally. However, the use of Ad5 as an anti-cancer agent may be hampered by naturally high seroprevalence rates to Ad5 coupled with infection of healthy cells via native receptors. To explore whether alternative natural adenoviral tropisms are better suited to GBM therapeutics, we pseudotyped an Ad5 based platform with the fiber knob protein from alternative serotypes. We demonstrate that the adenoviral entry receptors coxsackie and adenovirus receptor (CAR) and CD46 are highly expressed by both GBM and healthy brain tissue, whereas Desmoglein 2 (DSG2) is expressed at low level in GBM. We demonstrate that adenoviral pseudotypes, engaging CAR, CD46 and DSG2, effectively transduce GBM cells. However, the presence of these receptors on non-transformed cells presents the possibility of off-target effects and therapeutic transgene expression in healthy cells. To enhance specificity of transgene expression to GBM, we assessed the potential for tumour specific promoters hTERT and survivin to drive reporter gene expression selectively in GBM cell lines. We demonstrate tightly GBM specific transgene expression using these constructs, indicating that the combination of pseudotyping and tumour specific promoters approaches may enable the development of efficacious therapies better suited to GBM.

Drug induced liver injury (DILI) is the most common cause of acute liver failure and 5-10% of patients hospitalized for jaundice are diagnosed with DILI. For a diagnosis of DILI to be made, there should be exclusion of other etiologies of liver injury and the use of a precipitator drug, latency of symptoms, and resolution of liver injury once the offending drug is identified and discontinued. In our case report, we present a patient with idiosyncratic hepatocellular pattern DILI after two doses of ocrelizumab for treatment of multiple sclerosis. Ocrelizumab was given 16 and 27 days prior to the onset of icterus, jaundice, and fatigue, in a patient without the evidence of prior exposure to hepatitis B virus. At presentation labs revealed severe acute hepatocellular liver injury with R factor of 30.42, marked hyperbilirubinemia, and transient hypoalbuminemia. No evidence of latent or active hepatitis B infection was detected. Drug dechallenge led to return of liver chemistries to near-normal levels 31 days after the onset of her symptoms. This case indicates DILI diagnosis associated with the use of ocrelizumab, and warrants careful monitoring of liver functions in patients even in the absence of hepatitis B.

L-Theanine, a unique non-protein amino acid, is an important bioactive component of green tea. Previous studies have shown that L-theanine has many potent health benefits, such as anti-anxiety effect, regulation of immune response, relaxing neural tension, reducing oxidative damage. However, little is known concerning whether L-theanine can improve the clearance of mitochondrial DNA (mtDNA) damage in organisms. Here, we reported that L-theanine treatment increased ATP production and improved mitochondrial morphology to extend the lifespan of UVC-exposed nematodes. Mechanistic investigations showed that L-theanine treatment enhanced the removal of mtDNA damage and extended lifespan by activating autophagy, mitophagy, mitochondrial dynamics, and mitochondrial unfolded protein response (UPRmt) in UVC-exposed nematodes. In addition, L-theanine treatment also up-regulated the expression of genes related to mitochondrial energy metabolism in UVC-exposed nematodes. Our study provided a theoretical basis for the possibility that tea drinking may prevent mitochondrial related diseases.

In drilling small holes with diameters of 1 mm or less, minute clogging and twining of chips or adhesion of the workpiece material can become factors in causing breakages of the drill bit; moreover, it can be difficult to identify the machining state. Acoustic emission (AE) sensing is a nondestructive inspection technique that measures the elastic-stress waves that are generated when a material is deformed and fractured. AE sensing permits highly sensitive measurements to be made without changing the rigidity of the experimental system, unlike force sensing of cutting resistance, etc. In the present study, attempts were made to identify the machining state and tool wear, and to predict abnormalities in small-diameter drilling by using the change in the frequency of AE signal waveforms arising from deformation and fracture. It was shown that it is possible to predict the breakage of the drill bit by detecting the high-frequency AE signals caused by adhesion. In addition, a correlation map of the AE frequency spectrum for identifying the machining state in a drilling operation is suggested.

Three genera of very large volant birds existed for most of the Pliocene: the Pelagornithidae seabirds; the large North American Teratornithidae and the stork Leptoptilos falconeri in Africa and Asia. All became extinct around 3 Ma. The reasons for their demise are puzzling, as the Pelagornithidae had a world-wide evolutionary history of more than 50 Ma, smaller teratorns were still extant in the Holocene and smaller stork species are still globally extant. Extant large birds have a common critical takeoff airspeed suggesting a biomechanical limit in terms of power, risk and launch speed, and simulations of the flight of these extinct species suggest that at 1 bar they would have exceeded this value. Estimates for the Late Pliocene atmospheric density are derived from marine and terrestrial isotopes as well as resin chemistry, both approaches suggesting a value of about 1.2 bar, which drops to present levels during the period 3.3 to 2.6 Ma, thus a loss in atmospheric density may have caused biomechanical and ecological stress contributing to their extinction and/or development of smaller forms. This hypothesis is examined in terms of a possible mechanism of atmospheric mass loss and how this would be seen in the geological record. At 1.2 bar all the extinct species present takeoff airspeeds similar to large extant volant birds and which match the expected power and kinetic energy levels.

Introduction: In recent years, platelets have been in short supply and high demand. Approximately one in five cardiac surgery patients require platelets. In our safety-net hospital, however, the incidence is over 40%. Renal dysfunction, long cardiopulmonary bypass (CPB) times, and absence of tranexamic acid (TXA) are common risk factors for requiring platelet transfusions. Methods: Our hypothesis was fewer platelets would be transfused within two hours after bypass under these three conditions: creatinine is low, predicted surgery duration is short, and TXA is uniformly administered. Our anesthesia department designed this retrospective before-and-after observational study when the surgery department decided to narrow preoperative criteria respective to these three elements. The Institutional Review Board of Louisiana State University Health Sciences Center Shreveport approved of the protocol and waived individual informed consent. We compared timing of platelet transfusions (within 7 days) in consecutive patients who had CPB during the first ninety days of 2022 to those in 2023 using t-tests in SAS 9.3. Confounders included age, weight, anticoagulants, gender, and the platelet counts and hemoglobin immediately prior to platelet transfusion. Secondary outcomes were postoperative day two creatinine and other components transfused. Results: Preoperatively creatinine tended to be higher in 2022 at 1.5 vs 1.1, reaching significance postoperatively at 1.9 vs 1.1 (p=0.02). Bypass times decreased from 174 to 124 minutes (p=0.06). TXA use increased from 18 of 28 to 26 of 29 patients. Platelet counts increased on bypass from 142 to 173 (p=0.06). Platelet and hemoglobin nadirs were higher (day 3: 8g/dL vs 8.8, p=0.04; 98 vs 138, p=0.005). Platelet units transfused per patient tended to increase (0.75+/-1 vs 0.93+/-1.5); if exposed, patients tended to receive more units (2.1+/-1.3 vs 2.5+/-1.4) sooner. Changes in transfusions for red cells were nonsignificant at 1.97 per patient to 1.21, cryoprecipitate 0.36 to 0.69, and FFP 0.93 to 0.83. Conclusions: This is the first study examining timing of platelet transfusions after bypass. In the present investigation, we measured platelet count during bypass and prothrombin hours after arrival in the intensive care. Platelets were often administered in sets of two because of scarce immediate supply, partly from lack of an agitator table. More importantly, these data support a need for point-of-care thromboelastograms intraoperatively, but the cost has been prohibitive. Some centers’ algorithms list triggers for transfusion by fibrinogen and prothrombin times, available immediately after separation from bypass.

Kamchatka berries (Lonicera caerulea L.) are known for their high content of phenolic compounds or vitamins, which is reflected in their antibacterial, detoxifying and anti-inflammatory properties. They are used in the production of jams, juices, wines and as natural dye. A bioferment was prepared from the pomace of the Kamchatka berry varieties Aurora and Indigo Gem and the strains Saccharomyces cerevisiae and Lacticaseibacillus paracasei, which was used to prepare a cosmetic preparation with a concentration of 5% in accordance with the guidelines of the COSMOS certification body. Conducted physico-chemical and organoleptic analyses and bioactive profile characterisation (UHPLC-DAD and UHPLC-ESI-MS/MS). The results showed that the presence of caffeic acid 4.47 ± 0.07 mg/100g was detected after fermentation of Kamchatka berry pomace. Vitamin C content increased by 141% after fermentation of Kamchatka berry pomace. The results of stability tests showed that in the process of physicochemical analysis of cosmetic preparation with bioferment of Kamchatka berry pomace the pH should oscillate in the range of 4.38-4.76 ± 0.01. Stability tests showed that the cosmetic should be protected from high temperatures and UV radiation and proved that the product is stable under changing conditions, resulting in lower transport and storage costs.

A sixty-six-year-old woman with a strong family history of breast cancer noted gradual onset of axillary lymph node enlargement in 2019. Axillary lymph node biopsies disclosed Lymph node involvement by Chronic Lymphocytic Leukemia (CLL/SLL). Immunophenotype analysis of nodal tissue and of bloodstream leukemic cells in immunohistochemistry and flow cytometry and next generation molecular diagnostics confirmed CLL/SLL. Replicate absolute peripheral blood lymphocyte counts in excess of 5.0 x 10e3/microliter confirmed the numerical threshold for diagnosis of Chronic Lymphocytic Leukemia in the bloodstream. FISH studies disclosed an immunoglobulin “mutation negative” CLL/SLL genotype without a light chain restriction pattern. No translocations or germline mutations were present. Borrelia spirochetes in the bloodstream were detected with simultaneous high spirochetemia of both borrelia miyamotoi and borrelia burgdorferi. FISH hybridization of leukemic lymphocytes disclosed extensive borrelia invasion of the cytoplasm and of the nucleus compartments of CLL/SLL tumor cells. Retrospective studies of the patient’s archival stored blood smears obtained three years prior in 2016 at age 63 disclosed no evidence of CLL/SLL but confirmed asymptomatic bloodstream borrelia miyamotoi and borrelia burgdorferi borrelia infection. Lyme serology had been reported as negative in 2016. Additionally, retrospective FISH DNA hybridizations focused on preleukemic bloodstream Lymphocytes disclosed rare borrelia spirochetal adherence to benign blood lymphocytes in the year 2016 in the preleukemic blood smears. This case report is the very first to describe precursor chronic asymptomatic Lyme borreliosis and Miyamotoi borrelia bloodstream infections three years prior to the diagnosis of Rai Stage 1 Chronic Lymphocytic leukemia.

The X-ray emission from a supernova remnant (SNR) is a powerful diagnostic of the state of the shocked plasma, and, given a model, can be used to determine the energy of the explosion, the age of the SNR and the density of the surrounding medium. Observed properties are shock radius, electron temperature (kTe) and emission measure (EM) of the shocked-gas. The standard and XSPEC definitions have an important difference. The XSPEC definition is superior for SNRs, which have components with low hydrogen abundance. SNR model calculations are based on hydrodynamic solutions for fluid variables of density, pressure and velocity. The relations between fluid variables and kTe or EM depend on composition, ionization state and electron-ion temperature ratio (Te/TI). Here the effects of composition, ionization and Te/TI on standard and on XSPEC versions of kTe and EM are investigated.

Many protein expression systems are primary utilised to produce a single, specific recombinant protein. In contrast, most biological processes such as virus assembly rely upon a complex of several interacting proteins rather than the activity of a sole protein. The high complexity of the baculovirus genome, coupled with a multiphase replication cycle incorporating distinct transcriptional steps, made it the ideal system to manipulate for high-level expression of a single or co-expression of multiple foreign proteins within a single cell. We have developed and utilised a series of recombinant baculovirus systems to unravel the sequential assembly process of a complex non-enveloped model virus, Bluetongue virus (BTV). The high protein yields expressed by the baculovirus system not only facilitated structure-function analysis of each viral proteins but were also advantageous to crystallography studies and supported the first atomic level resolution of a recombinant viral protein, the major BTV capsid protein. Further, the formation of recombinant double-shelled virus-like particles (VLPs) provided insights into the structure-function relationships among the four major structural proteins of the BTV whilst also representing a potential candidate for a viral vaccine. The baculovirus multi-gene expression system facilitated the study of structurally complex viruses (both non-enveloped and enveloped viruses) and heralded in a new generation of viral vaccines.

Berberis vulgaris (L.) has remarkable ethnopharmacological properties and is widely used in traditional medicine. The present study investigates B. vulgaris stem bark (Berberidis cortex) by extraction with 50% ethanol. The main secondary metabolites were quantified, resulting in a polyphenols content of 17.6780 ± 3.9320 mg Eq Tannic acid / 100 g extract, phenolic acids amount of 3.3886 ± 0.3481 mg Eq Chlorogenic acid / 100 g extract and 78.95 µg/g berberine. The dried hydro-ethanolic extract (BVE) was thoroughly analyzed using Ultra-High Performance Liquid Chromatography coupled with High-Resolution Mass Spectrometry (UHPLC–HRMS/MS) and HPLC and 40 bioactive phenolic constituents were identified. Then, the antioxidant potential of BVE was evaluated using three methods; our results could explain the protective effects of Berberidis cortex EC50FRAP = 0.1398 mg/mL, IC50ABTS = 0.0442 mg/mL, IC50DPPH = 0.2610 mg/mL compared to ascorbic acid (IC50 = 0.0165 mg/mL). Next, the acute toxicity and teratogenicity of BVE and Berberine - Berberine sulfate hydrate (BS) - investigated on Daphnia sp reported significant BS toxicity after 24 h; BVE revealed considerable toxicity after 48 hours and induced embryonic developmental delays. Finally, the anticancer effects of BVE and BS were evaluated on different tumor cell lines after 24 and 48 hours of treatments. The MTS assay evidenced a dose- and time-dependent antiproliferative activity, higher on BS than BVE. The strongest diminution of tumor cell viability was recorded on breast (MDA-MB-231), colon (LoVo) cancer, and OSCC (PE/CA-PJ49) cell lines after 48 h of exposure (IC50 &lt; 100 µg/mL). However, no cytotoxicity was reported on normal epithelial cells (HUVEC) and hepatocellular carcinoma (HT-29) cell lines. Extensive data analysis supports our results, showing a significant correlation between the BVE's concentration, phenolic compounds content, antioxidant activity, exposure time, and the viability rate of various normal cells and cancer cell lines.

Mango twig-tip dieback (MTTD) is a new type of mango decline, but its impact on the trees’ mineral nutrition is unknown. This study was conducted to determine the effect of MTTD infection on the nutrient status, balance, and resorption efficiency (RE) of mango. Leaf nutrient concentrations and deviation from the optimum percentage (DOP) indices of ‘Kensington Pride’ (KP) mango trees with low (LD) and high (HD) levels of MTTD infections were analyzed to compare the foliar nutrition status and nutrient balance between the LD and HD trees. Moreover, the nutrient resorption efficiency of MTTD-infected dried leaves (RED) was compared with the resorption efficiency of healthy (RES) leaves of KP mangoes. The concentrations of Ca, Mg, Cu, Fe, Mn, and Zn were lower in the HD trees than in the LD trees. But the K content was higher in the HD trees, and its DOP index was sufficient, while the K concentration was low and deficient level in LD trees. Moreover, DOP indices for Ca, Mn, and Zn were less deficient in LD trees than in HD trees, and overall nutrient imbalances were exacerbated in HD trees. RED was significantly lower than RES for N, P, S, Cu, Fe, and Zn but significantly higher than RES for K. The study underscores the significant influence of MTTD on the mineral nutrition of KP mangoes, revealing distinct nutrient variations between trees with low and high MTTD infection levels. These findings have important implications for mango crop management, emphasizing the need for targeted nutrient interventions to address imbalances induced by MTTD and enhance the overall health and resistance of mango trees against MTTD infection.

Carcinus maenas (the “shore crab” or “European green crab”) is a very proficient invader (considered to be one of the world’s 100 worst invaders by the IUCN) due to its phenotypic plasticity, wide temperature and salinity tolerance, and an extensive omnivorous diet. Native to Atlantic Europe, it has established two well‐studied nonindigenous populations in the northwestern Atlantic and northeastern Pacific and less‐studied populations in Australia, Argentina and South Africa. Green crabs are eurythermal and euryhaline as adults, but they are limited to temperate coastlines due to more restrictive temperature requirements for breeding and larval development. They cannot tolerate wave‐swept open shores so are found in wave‐protected sheltered bays, estuaries and harbors. Carcinus maenas has been the subject of numerous papers, with over 1000 published in the past decade. This review provides an up‐to‐date account of the current published information on the life history and population dynamics of this very important species, including genetic differentiation, habitat preferences, physical parameter tolerances, reproduction and larval development, sizes of crabs, densities of populations, sex ratios, ecosystem dynamics and ecological impacts in the various established global populations of green crabs.

Amidst worsening climate change, drought stress imperils global agriculture, jeopardizing crop yields and food security, necessitating urgent exploration of sustainable methods like biopriming, harnessing beneficial microorganisms to bolster plant resilience. Recent research has revealed diverse biological compounds with versatile applications produced by Schizophyllum commune, rendering this fungus as a promising contender for biopriming applications. For the first time this study aimed to investigate,the potential of S. commune exo- (EPSH) and intra-PSH (IPSH), isolated from two strains: Italian (ITA) and Serbian (SRB) under submerged cultivation, in enhancing the resilience of Pisum sativum L. seeds through biopriming technique. Testing of seed quality of bioprimed, hydroprimed, and unprimed seeds was done using a germination test, under optimal and drought conditions. In optimal conditions, the IPSH SRB increased germination energy by 5.50% compared to the control, while the highest percentage of germination (94.70%) was shown after biopriming with PSH isolated from the ITA strain. Additionally, all assessed treatments resulted in a boost in seedling growth and biomass accumulation, where the ITA strain demonstrated greater effectiveness in optimal conditions, whereas the SRB strain showed superiority in drought conditions. The drought tolerance indices increased significantly in response to all examined treatments during the drought, with EPSH ITA (23.00%) and EPSH SRB (24.00%) demonstrating the greatest effects. Results demonstrate a significant positive influence of fungal PSH, indicating their potential as biopriming agents and offers insights into novel strategies for agricultural resilience in the face of changing environmental conditions.

In the present manuscript, we report new insights into the concept of (a)synchronicity in Diels-Alder (DA) reactions in the framework of the reaction force analysis, in conjunction with natural population calculations and atomic resolution of energy derivatives along the intrinsic reaction coordinate (IRC) path. Our findings suggest that the DA reaction transitions between a preferentially concerted mechanism to a stepwise one in a 0.10 Å window of synchronicity indices, ranging from 0.90 to 1.00 Å. We have also shown that the relative position of the global minimum of the reaction force constant with respect to the TS is an alternative and quantifiable indicator of the (a)synchronicity in DA reactions. Moreover, the atomic resolution of energy derivatives reveals that the mechanism of the DA reaction involves two inner elementary processes associated with the formation of each of the two C-C bonds. This resolution goes on to indicate that, in asynchronous reactions, the driving and retarding components of the reaction force are mostly due the fast and slow-forming C-C bonds (elementary process) respectively, while in synchronous ones both elementary processes retard and drive the process concomitantly and equivalently.

According to statistics from the Food and Agriculture Organization, the world population will increase to about 91 million (Asia 51 million, Africa 19 million). A rise in the world’s population means an increased need for food. However, climate change has caused desertification and unpredictable weather, creating problems in the supply and demand of food. Sweet potato (Ipomoea batatas) is an alternative to solving the food problem, as it is one of the world’s most important food crops, especially in developing countries. The tuberous roots of sweet potato are usually used as staple food, animal feed, industrial material, or raw material for alcohol production. In the future, more variations of sweet potato will be needed for breeding this crop. Recently, molecular markers developed for sweet potato have demonstrated good potential for use in genetic selection. In this study, a cDNA library was constructed from the total RNA of sweet potato leaves. A total of 789 copies of the cDNA were cloned in Escherichia coli by employing the pGEM-T Easy vector. Sequencing was carried out by Solgent Co. (Korea). As many as 579 expressed sequence tag–simple sequence repeat (EST-SSR) markers were designed (73.38%) from the known cDNA nucleotide base sequences. The lengths of the developed EST-SSR markers ranged from 100 to 499 bp (average length 238 bp). Their motif sequence types were varied, with most being dinucleotides and pentanucleotides, and the most commonly found motifs were CAGAAT (29.0%) and TCT (2.8%). Based on these SSR-containing sequences, 619 pairs of high-quality SSR primers were designed using WebSat and Primer3web. The total number of primers designed was 144. Polymorphism was evident in 82 EST-SSR markers among 20 Korean sweet potato cultivars tested and in 90 EST-SSR markers in the two parents of a mapping population, Yeseumi and Annobeny. In this study, the hexaploid sweet potato (2n = 6x = 90) EST-SSR markers were developed in the absence of full-sequence data. Moreover, by acting as a molecular tag for particular traits, the EST-SSR marker can also simultaneously identify information about the corresponding gene. These EST-SSR markers will allow the molecular analysis of sweet potato to be done more efficiently. Thus, we can develop high-quality sweet potato while overcoming the challenges from climate change and other unfavorable conditions.

Ever since Varela and Maturana proposed the concept of autopoiesis as the minimal requirement for life, there has been a focus on cellular systems that erect topological boundaries to separate themselves from their surrounding environment. Here we reconsider whether the existence of such a spatial boundary is strictly necessary for self-producing entities. This work presents a novel computational model of a minimal autopoietic system inspired by dendrites and molecular dynamics simulations in three-dimensional space. A series of simulation experiments where the metabolic pathways of a particular autocatalytic set are successively inhibited until autocatalytic entities that could be considered autopoietic are produced. These entities maintain their distinctness in an environment containing multiple identical instances of the entities without the existence of a topological boundary. This gives rise to the concept of a metabolic boundary which manifests as emergent self-selection criteria for the processes of self-production without any need for unique identifiers. However, the adoption of such a boundary comes at a cost, as these autopoietic entities are less suited to their simulated environment than their autocatalytic counterparts. Finally, this work showcases a generalized metabolism-centered approach to the study of autopoiesis that can be applied to both physical and abstract systems alike.

Cultivated adlay or Job’s tear (Coix lacryma-jobi L.) is an important food crop having numerous therapeutic and nutraceutical health benefits. Our study aimed to determine nutrients, minerals, fatty acid composition, and functional groups of seven wild Adlay accessions (brown, black, yellow, grey, green, off-white, and purple) to find out their scope as cereal crops using simple, rapid, and modern analytical techniques. Results revealed variations among bulk densities, specific densities, percent empty spaces, and corresponding grain counts per 10g of sample are valuable characteristics in distinguishing the accessions. Contents of fat, protein, ash, and fibre were found to be comparable to cultivated Adlay. Brown adlay was measured with the highest protein, fat, and fibre contents, 15.82%, 4.76% and 2.37%, respectively. Phosphorus, potassium, calcium, and sodium ranged 0.3% - 2.2%, whereas boron, iron, copper, zinc, and manganese were in the range 1.6mg/kg - 20.8mg/kg. Wild adlay triglyceride composition constituted of polyunsaturated fatty acids as primary fraction followed by olein and palmitic acid as prominent fatty acids. Distinguishing functional groups expressed infra-red frequencies in narrow bands and fingerprint region of proteins associated with out-of-plane region evident structural differences among adlay accessions. Frequency of functional groups in seven accessions indicated black genotype promising for varietal development.

In this paper, we propose an imagined speech-based brain wave pattern recognition using deep learning. Multiple features were extracted concurrently from eight-channel Electroencephalography (EEG) signals. To obtain classifiable EEG data with fewer number of sensors, we placed the EEG sensors on carefully selected spots on the scalp. To decrease the dimensions and complexity of the EEG dataset and to avoid overfitting during the deep learning algorithm, we utilized the wavelet scattering transformation. A low-cost 8-channel EEG headset was used with MATLAB 2023a to acquire the EEG data. The Long-Short Term Memory Recurrent Neural Network (LSTM-RNN) was used to decode the identified EEG signals into four audio commands: Up, Down, Left, and Right. Wavelet scattering transformation was applied to extract the most stable features by passing the EEG dataset through a series of filtration processes. Filtration has been implemented for each individual command in the EEG datasets. The proposed imagined speech-based brain wave pattern recognition approach achieved a 92.50% overall classification accuracy. This accuracy is promising for designing a trustworthy imagined speech-based Brain-Computer Interface (BCI) future real-time systems. For better evaluation of the classification performance, other metrics were considered, and we obtained 92.74%, 92.50% and 92.62% for precision, recall, and F1-score, respectively.

Lactobacilli are considered an inexhaustible source of potentially bioactive substances; indeed, several products from their metabolism are known to have immunomodulatory and anti-inflammatory activity. Recently, we demonstrated that cell-free supernatants (CFS) obtained from Lactobacillus (L.) acidophilus, L. plantarum, L. rhamnosus and L. reuteri can impair Candida pathogenic potential in an in vitro model of epithelial vaginal infection. This effect could be ascribed to a direct effect of living lactobacilli on Candida virulence and to the production of metabolites which are able to impair fungal virulence. In the present work, stemming from those data, we deepened our knowledge on the CFS from these 4 lactobacilli by performing a metabolomic analysis to better characterize their composition. By using an untargeted metabolomic approach, we detected consistent differences in the metabolites produced by these four different lactobacilli. Interestingly, L. rhamnosus showed the most peculiar metabolic profile. Specifically, after a hierarchical clustering analysis in positive and negative ionization mode, L. rhamnosus showed a specific area of significant overexpressed metabolites that strongly differed from the same area in other lactobacilli. In this area, inosine was identified among the overexpressed metabolites of L. rhamnosus. This molecule has been described to have antioxidant, anti-inflammatory, anti-infective and neuroprotective properties. The biological significance of its overproduction by L. rhamnosus might be important in its probiotic and/or postbiotic activity.

Six bacterial strains with differing abilities to produce varying concentrations of Indole Acetic Acid were tested individually and in consortia for plant growth promoting and fitness related traits of Cicer arietinum. In all experiments the presence of the nitrogen fixer Mesorhizobium ciceri resulted in increased biomass production. In the absence of this strain, IAA Psedomonas putida and Bacillus megaterium hinder plant growth and fitness related traits. The application of mixes of the three strains always resulted in better plant performance when M. ciceri was present. Whereas P. putida has a noticeable plant growth-promoting effect B. megaterium resulted less effective. The low levels of IAA produced by the selected strains had a significantly greater positive effect on plant biomass accumulation, flower, pods and seed production as well as on total plant nitrogen and nitrogen concentration in seed than high IAA producer strains.

Plants have been used in alternative medicine for centuries in the treatment of many diseases with the metabolites they contain. The goal of this work was to investigate the phenolic profile, antioxidant capacity and biological activity of I. helenium subsp. pseudohelenium extracts. Phe-nolic (HPLC) substances in leaf ethanol (L-EtOH), leaf pure water (L-PW), root ethanol (R-EtOH), and root pure water (R-PW) extracts of Inula helenium subsp. pseudohelenium plant were investi-gated. Also, in vitro the antimicrobial (hollow agar), antioxidant (DPPH, ABTS.+, FRAP, CU-PRAC), antiproliferative (MTT assay against HT-29, MCF-7 and L-929), and DNA (Agarose gel electrophoresis) protective activities of the samples were examined. Although gallic acid was not detected in the extracts, the presence of curcumin was detected only in EtOH extracts. L-EtOH exhibited the best antimicrobial activity. According to the antioxidant results, it was found that the L-EtOH extract had an activity profile close to the standard antioxidants in general. It was also found that the L-EtOH extract stabilized the DNA by disrupting the scavenging effect of H2O2+DMSO. According to the antiproliferative activity results, EtOH extracts exhibited the strongest effect, especially against MCF7. When evaluated in general terms, it was found that L-EtOH extract showed better activity than other extracts. It is important to conduct more in vivo and in vitro studies after isolating the active components of extracts e.g. L-EtOH, which have good effects in terms of biological activity.

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.

This paper presents a method for a decentralised peer-to-peer software license validation system using cryptocurrency blockchain technology to ameliorate software piracy, and to provide a mechanism for software developers to protect copyrighted works. Protecting software copyright has been an issue since the late 1970's and software license validation has been a primary method employed in an attempt to minimise software piracy and protect software copyright. The method described creates an ecosystem in which the rights and privileges of participants are observed.

Background: We previously developed a refined, tumor selective adenovirus, Ad5NULL-A20, har-boring tropism ablating mutations in each major capsid protein, to ablate all native means of infection. We incorporated a 20mer peptide (A20) in the fiber knob for selective infection via αvβ6 integrin, a marker of aggressive epithelial cancers. Methods: To ascertain the selectivity of Ad5NULL-A20 for αvβ6 positive tumor cell lines of pancreatic and breast cancer origin, we performed reporter gene and cell viability assays. Biodistribution of viral vectors in mice harboring xenografts with low, medium, and high αvβ6 levels was quantified by qPCR for viral genomes 48 hours post intravenous administration. Results: Ad5NULL-A20 vector transduced cells in an αvβ6 selective manner, whilst cell killing me-diated by oncolytic Ad5NULL-A20 was αvβ6 selective. Biodistribution analysis following intrave-nous administration into mice bearing breast cancer xenografts demonstrated that Ad5NULL-A20 resulted in significantly reduced liver accumulation coupled with increased tumor accumulation compared to Ad5 in all three models, with tumor: liver ratios improved as a function of αvβ6 expression. Conclusions: Ad5NULL-A20 based virotherapies efficiently target αvβ6 integrin positive tumors following intravenous administration, validating the potential of Ad5NULL-A20 for systemic ap-plications, enabling tumor selective overexpression of virally encoded therapeutic transgenes.

Particle Swarm Optimization (PSO) is a metaheuristic global optimization paradigm that has gained prominence in the last two decades due to its ease of application in unsupervised, complex multidimensional problems which cannot be solved using traditional deterministic algorithms. The canonical particle swarm optimizer is based on the flocking behavior and social co-operation of birds and fish schools and draws heavily from the evolutionary behavior of these organisms. This paper serves to provide a thorough survey of the PSO algorithm with special emphasis on the development, deployment and improvements of its most basic as well as some of the very recent state–of-the-art implementations. Concepts and directions on choosing the inertia weight, constriction factor, cognition and social weights and perspectives on convergence, parallelization, elitism, niching and discrete optimization as well as neighborhood topologies are outlined. Hybridization attempts with other evolutionary and swarm paradigms in selected applications are covered and an up-to-date review is put forward for the interested reader.

Berberis vulgaris L. (Berberidaceae) is a shrub that has been widely used in European folk medicine as an anti-inflammatory and antimicrobial agent. The purpose of our study was to elucidate the mechanisms of antiproliferative action of the plant’s methanolic root extract (BVR) against colon cancer cells. Cytotoxicity and pro-apoptotic activity were determined in human colon adenocarcinoma cell lines (LS180 and HT-29) and control colon epithelial CCD841 CoN cells. According to the MTT assay, after 48 h of cell exposure, the IC50 values were as follows: 4.3; 46.1 and 50.2 µg/mL for LS180, HT-29, and CCD841 CoN cells, respectively, showing the greater sensitivity of cancer cells to BVR. The Cell Death Detection ELISAPLUS kit demonstrated that BVR induced programmed cell death only against HT-29 cells. RT-qPCR with relative quantification method showed significant changes in the expression of genes related to apoptosis in both colon cancer cell lines. The genes BCL2L1 (126.84-366.66%), BCL2L2 (277.08-330.12%), CASP3 (180.36-261.36%) and CASP9 (158.08-213.46%) had significantly elevated expression, while BCL2 (23.08-52.06%) had reduced expression. Furthermore, in a panel of antioxidant tests, BVR showed positive effects (63.93±0.01, 122.92±0.01, and 220.29±0.02 mg Trolox equivalents (TE)/g in the DPPH•, ABTS•+ and ORAC assays, respectively). In the lipoxygenase (LOX) inhibition test, BVR revealed 62,60±0.87% of enzyme inhibition. The chemical composition of BVR was determined using UHPLC-UV-CAD-MS/MS analysis and confirmed the presence of several known alkaloids, including berberine, as well as other alkaloids and two derivatives of hydroxycinnamic acid (ferulic and sinapic acid hexosides). This is the first such extensive assessment of the biological activity of BVR. The results are very promising and encourage for the use of BVR as a comprehensive chemopreventive agent (anti-inflammatory, antioxidant, and pro-apoptotic) in colorectal cancer.

Camelina (Camelina sativa L.) is an oilseed with potential for use as a raw material in second-generation biofuels. Camelina has a seed yield of up to 2380 kg ha^-1 and contains around 45% fatty acids. Selection of a suitable site is critical for production optimization. The objective of this study was to determine Chilean agro-climatic suitability for establishing camelina as a productive alternative. Climate and soil requirements and geographical restraints were evaluated for the species, considering the climatological characteristics of its regions of origin, as well as regions where camelina is successfully grown in the rest of the world. The variables considered include factors (maximum temperatures of the warmest month, water deficits, and degree days) and limitations (altitude, geomorphology, and current land use), which permitted the evaluation of the national territory for a certain level of suitability. It was determined that 1.3% of the national territory (960,664 ha) has some degree of suitability for camelina adoption. Between the Biobío and Los Lagos regions, 49.0% of land (471,203 ha) is in the category of without thermic restrictions, with mild water restrictions, and mild soil restrictions or without information, which can be used for camelina production. The Los Ríos region had 21.4% surface area (321,176 ha) with some level of suitability for camelina, the most suitable region to establish this crop in Chile.

Malware analysis is fundamental for defending against prevalent cyber security threats, and requires a means to deploy and study behavioural software traits as more sophisticated malware is developed. Traditionally, virtual machines are used to provide an environment that is isolated from production systems so as to not cause any adverse impact on existing infrastructure. Malware developers are fully aware of this and so will often develop evasion techniques to avoid detection within sandbox environments. In this paper, we conduct an investigation of anti-evasion malware triggers for uncovering malware that may attempt to conceal itself when deployed in a traditional sandbox environment. To facilitate our investigation, we developed a tool called MORRIGU that couples together both automated and human-driven analysis for systematic testing of anti-evasion methods using dynamic sandbox reconfiguration techniques. This is further supported by visualisation methods for performing comparative analysis of system activity when malware is deployed under different sandbox configurations. Our study reveals a variety of anti-evasion traits that are shared amongst different malware families, such as sandbox `wear-and-tear', and Reverse Turing Tests (RTT), as well as more sophisticated malware samples that require multiple anti-evasion checks to be deployed. We also perform a comparative study using Cuckoo sandbox to demonstrate the limitations of adopting only automated analysis tools, to justify the exploratory analysis provided by MORRIGU. By adopting a clearer systematic process for uncovering anti-evasion malware triggers, as supported by tools like MORRIGU, this study helps to further the research of evasive malware analysis so that we can better defend against such future attacks.

Neuroinflammation is considered to be a significant component in a range of neuropathologies. Unfortunately, whilst its role is well recognized, the options for therapeutic intervention are limited. As such, there is a need to identify novel targets in order to increase treatment options. Given its role as both a neurotransmitter and an immune modulator, substance P and its NK1 receptor have been widely studied as a potential therapeutic target. There is evidence that NK1 receptor antagonists may exert beneficial effects in a range of conditions, including traumatic brain injury and stroke. Blocking the NK1 receptor has been shown to reduce blood-brain barrier dysfunction, reduce cerebral oedema, and reduce the levels of pro-inflammatory cytokines. These actions are associated with improved survival and functional outcomes. The NK1 receptor has also been shown to be involved in the inflammatory reaction to CNS infection, and hence antagonist may have some benefit in reducing infection-driven inflammation. However, the NK1 receptor may also play a role in the host immune response to infection, and so here, the potential beneficial and detrimental effects need to be carefully balanced. As such, the purpose of this review is to provide a summary of the involvement of substance P in acute inflammation, particularly in the context of traumatic brain injury and stroke.

Although the water absorption feature (WAF) at 970 nm is not very well-defined, it may be used alongside other indices to estimate the canopy water content. The individual performance of a number of existing vegetation water content (VWC) indices against the WAF is assessed using linear regression model. We developed a new Combined Vegetation Water Index (CVWI) by merging indices to boost the weak absorption feature. CVWI showed a promise in assessing the vegetation water status derived from the 970 nm absorption wavelength. CVWI was able to differentiate two groups of dataset when regressed against the absorption feature. CVWI could be seen as an easy and robust method for vegetation water content studies using hyperspectral field data.

The human adenovirus phylogenetic tree is split across seven species (A-G). Species D adenoviruses offer potential advantages for gene therapy applications, with low rates of preexisting immunity detected across screened populations. However, many aspects of the basic virology of species D, such as their cellular tropism, receptor usage and in vivo biodistribution profile, remain unknown. Here, we have characterized human adenovirus type 49 (HAdV-D49), a relatively understudied species D member. We report that HAdV-D49 does not appear to use a single pathway to gain cell entry but appears able to interact with various surface molecules for entry. As such, HAdV-D49 can transduce a broad range of cell types in vitro, with variable engagement of blood coagulation FX. Interestingly, when comparing in vivo biodistribution to adenovirus type 5, HAdV-D49 vectors show reduced liver targeting whilst maintaining transduction of lung and spleen. Overall, this presents HAdV-D49 as a robust viral vector platform for ex vivo manipulation of human cells and for in vivo applications where the therapeutic goal is to target the lung or gain access to immune cells in the spleen whilst avoiding liver interactions, such as intravascular vaccine applications.

This paper discusses the preliminary results of archaeological surveys conducted in the Juuku Region of north-central Kyrgyzstan on the south side of Lake Issyk kul. Our goal was to document ancient and contemporary agropastoral systems over a four millenia time period. During the surveys about 350 loci were identified as settlements, burial mounds, graves, single artifact finds, and artifact scatters (ceramic). The areas of Juuku Valley survey included two discrete polygons: Polygon 1, Lower Juuku at 1750 to 1950 m asl in elevation and Polygon 2, Chak Juuku or Upper Eastern Branch Juuku Valley at 2060 to 2100 m asl in elevation. Three radiometric dates and preliminary archaeobotanical studies were conducted at three exposed profile cuts. The methods included here are: (1) pedestrian surveys; (2) use of digital maps (Google Earth, Encarta); (3) placing archaeological loci within known chronological time periods; (4) AMS dating of charcoal samples collected from profile deposits; and (5) preliminary identification of plant remains found from archaeobotanical samples. The results of our research represent the first step toward inventorying and interpreting archaeological data in the Juuku Valley derived from field studies.

Grand challenges represent wicked problems that affect many people globally. To overcome grand challenges and sustain our existence as human beings, issues have become increasingly central, and in recent years have led to an increase in research and literature on grand challenges affecting both international business areas and multinational enterprises. The aim of this study is to assess the status of literature in all areas connected to multinational corporations and grand challenges, which are global issues with significant implications. From 2013 to 2023, the WoS database was used to investigate eight search terms from literature, and bibliometric and thematic analyses were carried out based on the principles of systematic literature analysis. The most focused areas of the research are performance, multinational enterprises, foreign direct investment, management, firms’ innovation, knowledge, international business, and impact. Asian, African, European, and other countries may emerge together in different clusters depending on whether the major challenges they are struggling with are similar or identical. the terms of grand challenges and innovation (open and social), technology transfer, R&amp;D internalization, digital transformation or technology and artificial intelligence in the literature of multinational enterprises indicates that these themes are used as a tool to solve grand challenges.

Opuntia ficus-indica (L.) Mill. belongs to the Cactaceae family and the genus Opuntia; it is a succulent plant that adapts to extreme climatic conditions. The aerial part of the plant consists of the cladodes, morphological changes of branches that appear green, are covered with thorns, and are essential to reduce excessive perspiration of water. The composition of cladodes is very varied, and the main constituents are water, fibers, polysaccharides, proteins, fatty acids, vitamins, sterols, minerals, and polyphenols. Polyphenols are responsible for many beneficial activities for human health, such as antioxidant, anti-inflammatory, antitumor, and nutritional properties. The purpose of this manuscript was to compare the properties of cladodes belonging to the same plant but with different stages of maturity. Relative extracts were tested both in vitro and on a cell line and antioxidant and anti-apoptotic properties were found. The antioxidant activity was tested by the ORAC test, the DPPH test, and the measurement of cellular accumulation of ROS. Anti-apoptotic activity was evaluated by the annexin/PI assay and measurement of caspases 9 and 3 expression. The results obtained have shown that the extracts considered possess antioxidant and anti-apoptotic properties. However, the different stages of maturity of cladodes are essential for the performance of both functions. In addition, important variations have been made in the dissolution of extracts that have brought greater safety in their use. In conclusion, this manuscript provides further information on cladodes of Opuntia ficus-indica, which can be used as adjuvants in many human pathologies.

This scoping review aims to identify the available evidence concerning the clinical and psychosocial impacts of the communication of oral potentially malignant disorders (OPMDs), and to map and analyze knowledge gaps regarding truth-telling about risk factors, malignant transformation, treatment, and follow-up approaches. Search strategy was performed using electronic databases (Medline/PubMed, Scopus, Embase, and Web of Science) and one grey literature database (Google Scholar). Studies focused on communicating the diagnosis of OPMDs and the patients' perceptions were included. Study selection and data extraction were performed by two authors in a two-phase process. Five publications were included in the qualitative analysis. Each publication involved a different study design, study population, types of OPMDs, and results on the important aspects of the professional-patient communication about the diagnosis of OPMDs. Although specific protocols on OPMDs communication have not yet been reported, there is an elevated interest on this topic since the strategies and skills on professional communication could provide better clinical outcomes to the patients. A list of recommendation strategies on how to communicate an OPMD diagnosis is proposed; however, future studies are still needed to design specific communication protocols for OPMD.

Consistent data is seldom available for whole-catchment flood modelling in many developing regions, thus this study demonstrates how the complementary strengths of open and readily available geospatial datasets and tools can be leverage to map flood risk within acceptable levels of uncertainty for flood risk management. Available fragmented remotely-sensed and in situ datasets (including hydrological data, altimetry, digital elevation model, bathymetry, aerial photos, optical and radar imageries) are systematically integrated using 2-dimensional CAESAR-LISFLOOD model to quantify and recreate the extent and impact of the historic 2012 flood in Nigeria. Experimental modelling, calibration and validation is undertaken for the whole Niger-South hydrological catchment area of Nigeria, then segmented into sub-domains for re-validation to understand how data variability and uncertainties impact on the accuracy of model outcomes. Furthermore, aerial photos are applied for the first time in the study area for flood model validation and to understand how different physio-environmental properties influence synthetic aperture radar flood delineation capacity in the Niger Delta region of Nigeria.

This article presents a low-cost insurance system developed for small-hold farms in disaster-prone regions, primarily using free Earth Observation (EO) data and Free Open Source Software (FOSS) – collectively termed sustainable geoinformatics - with a proprietary mobile phone app that enables verification. The study examined 30 farms in Risaralda department, Colombia. A Digital Elevation Model (12.5m pixels) from the ALOS PALSAR satellite sensor was used with a Geographical Information System (GIS) to map the terrain, drainage and geohazards of each farming district. Google Earth Engine (GEE) was used to carry out Time Series Analysis of 15 EO and weather datasets for 1998 to 2020. This analysis enabled the levels of risk from hydrometeorological hazards to be determined for each farm of the study, providing key data for the setting of insurance premiums. A parametric insurance product was piloted using GPS-tagged, time-stamped mobile phone photos to verify crop health. Key features of this insurance system are its low operational cost and rapid damage verification, relative to conventional approaches to farm insurance. It is an affordable form of insurance for small-scale farmers, with the rapid verification and payment of claims. This relatively fast, low-cost and affordable approach to insurance for small-scale farming enhances sustainable development by enabling policy-holder farmers to recover more quickly from disasters.

The chemical investigation of the anti-yeast methanol extract from the stem bark of Terminalia mantaly led to the isolation of seven compounds: 3-O-methyl-4-O-α-rhamnopyranoside ellagic acid (1), 3-O-mehylellagic acid (2), arjungenin or 2,3,19,23-tetrahydroxyolean-12-en-28-oïc acid (3), arjunglucoside or 2,3,19,23-tetrahydroxyolean-12-en-28-oïc acid glucopyranoside (4), 2α,3α,24-trihydroxyolean-11,13(18)-dien-28-oïc acid (5), stigmasterol (6), stigmasterol 3-O-β-D-glucopyranoside (7). Their structures were established by means of spectroscopic analysis and comparison with published data. Compounds 1-5 were tested in vitro for activity against three pathogenic yeast isolates, Candida albicans, Candida parapsilosis and Candida krusei. The activity of compounds 1, 2 and 4 were comparable to that of the reference compound fluconazole (MIC values below 32 µg/ml) against the three tested yeast isolates. They were also tested for inhibitory properties against four enzymes of metabolic significance: Glucose-6-Phosphate Deshydrogenase (G6PD), human erythrocyte Carbonic anhydrase I and II (hCA I and hCA II), Glutathione S-transferase (GST). Compound 4 showed highly potent inhibitory property against the four tested enzymes with overall IC₅₀ values below 4 µM and inhibitory constant (Ki) <3 µM.

The purpose of present work was to provide mineralogical insight in the rare earth element (REE) phases in bauxite residue to improve REE recovering technologies. Experimental work was performed by electron probe microanalysis with energy dispersive as well as wavelength dispersive spectroscopy and transmission electron microscopy. REEs are found as discrete mineral particles in bauxite residue. Their sizes range from < 1 μm to about 40 μm. In bauxite residue, the most abundant REE bearing phases are light REE (LREE) ferrotitanates, that form a solid solution between the phases with major compositions (REE,Ca,Na)(Ti,Fe)O3 and (Ca,Na)(Ti,Fe)O3. These are secondary phases formed during the Bayer process by an in-situ transformation of the precursor bauxite LREE phases. Comparing to natural systems, the indicated solid solution resembles loparite-perovskite series. LREE particles often have a calcium ferrotitanate shell surrounding them, that probably hinders their solubility. Minor amount of LREE carbonate and phosphate minerals as well as manganese-associated LREE phases are also present in bauxite residue. Heavy REEs occur in the same form as in bauxites, namely as yttrium phosphates. These results show that Bayer process has an impact on the initial REE mineralogy contained in bauxite. Bauxite residue as well as selected bauxites are potentially good sources of REEs.

Pharmacovigilance databases are showing evidence of injury in the context of the COVID-19 modified mRNA shots. According to recent publications, adverse event reports linked to the mRNA COVID-19 products largely point to the spike protein as an aetiological agent of adverse events, but we propose that the platform itself may be culpable. To assess the safety of current and future mRNA vaccines, further analysis on the risks due to the platform itself, and not specifically the expressed antigen. If harm can be exclusively and conclusively attributed to the spike protein, then it is possible that future mRNA vaccines expressing other antigens will be safe. If harms are attributable to the platform itself, then regardless of the toxicity, or lack thereof, of the chosen payload therein, the platform may be inherently unsafe, pending modification. In this work, we examine previous studies of RNA-based delivery by a lipid nanoparticle and break down the possible etiological elements of harm.

Adlay seed samples were collected from 3 adlay growing regions (Yeoncheon, Jeonnam and Eumseong regions) in Korea during 2012. Among all the samples collected, 400 seeds were tested for fungal occurrence by standard blotter and test tube agar methods and different taxonomic groups of fungal genera were detected. The most predominant fungal genera encountered were Fusarium, Phoma, Alternaria, Cladosporium, Curvularia, Cochliobolus and Leptosphaerulina. The occurrence of Fusarium species were 45.6% and based on the combined sequences of two protein coding genes, EF-1a, Beta-tubulin and phylogenetic analysis, 10 species were characterized as F. incarnatum (11.67%), F. kyushense (10.33%), F. fujikuroi (8.67%), F. concentricum (6.00%), F. asiaticum (5.67%), F. graminearum (1.67%), F. miscanthi (0.67%), F. polyphialidiom (0.33%), F. armeniacum (0.33%) and F. thapsinum (0.33%). The ability of these isolates to produce mycotoxins fumonisin (FUM) and zeralenone (ZEN) were tested by ELISA quantitative analysis method. The result revealed that fumonisin (FUM) was produced only by F. fujikuroi and zeralenone (ZEN) by F. asiaticum & F. graminearum. Mycotoxigenic species were then examined for their morphological characteristics to confirm their identity. Morphological observations of the species correlated well with their molecular identification and confirmed as F. asiaticum, F. fujikuroi and F. graminearum.

Cannabis has long been used for its medicinal and psychoactive properties. With the relatively new adoption of formal medicinal cannabis regulations worldwide, the study of cannabinoids, both endogenous and exogenous, has similarly flourished in more recent decades. In particular, research investigating the role of cannabinoids in regeneration and neurodevelopment has yielded promising results in vertebrate models. However, regeneration-competent vertebrates are few, whereas a myriad of invertebrate species have been established as superb models for regeneration. As such, this review aims to provide a comprehensive summary of the endocannabinoid system, with a focus on current advances in the area of endocannabinoid system contributions to invertebrate neurodevelopment and regeneration.

Humans learn from a lot of information sources to make decisions. Once this information is learned in the brain, spatio-temporal associations are made, connecting all these sources (variables) in space and time represented as brain connectivity. In reality, to make a decision, we usually have only part of the infor-mation, either as a limited number of variables, or limited time to make the decision, or both. The brain functions as spatio-temporal associative memory. Inspired by the ability of the human brain, a brain-inspired spatio-temporal associative memory was proposed earlier, that utilizes the NeuCube brain-inspired spiking neural network framework. Here we apply the STAM framework to develop STAM for neuroimaging data, on the cases of EEG and fMRI, resulting in STAM-EEG and STAM-fMRI. The paper shows that once a NeuCube STAM classification model is trained on a complete spatio-temporal EEG or fMRI data, it can be recalled using only part of the time series, or/and only part of the used variables. We evaluate accordingly the temporal association accuracy and spatial association accuracy. This is a pilot study that opens the field for the development of multimodal classification systems on other multimodal neuroimaging data, such as the also shown longitudinal MRI data, trained on complete data, but recalled on partial data collected across different settings, in different labs and clinics, that may vary in terms of variables, time of data collection, and other parameters. The proposed methods will allow also for brain diagnostic/prognostic marker discovery using spatio-temporal neuroimaging data.

Stream chemistry effectively integrates watershed ecosystem processes on both spatial and temporal scales. Streams of coastal areas integrate a more homogeneous, flat topography wherein there can be interactions between the stream and the body of water into which it drains, especially where tidal fluxes occur. The present study assessed water quality of Thompson Bayou, which comes to the campus of the University of West Florida in a wetland after flowing through 4 km of commercial and private property with associated impacts on water quality. Sampling was carried out for one year at eight discrete sites along Thompson Bayou from the UWF campus to the Escambia River. We used a portable field meter to measure temperature, pH, dissolved O2 (DO), and specific conductivity (SC). Except for temperature, all variables exhibited a spatial pattern of significant variation with distance, with consistent increases in DO and SC as the stream approached the river. These variables also exhibited a temporal pattern of significant seasonal variation, including—and especially—temperature. Data suggest that spatial and temporal patterns of water quality of Thompson Bayou are determined by (1) processing of water by the wetland, (2) interactions of the stream channel with upland forest stands, and (3) the tidal hydrology of the Escambia River.

Our wellbeing is greatly influenced by our childhood and adolescence, and the relationships that we form during those phases of our development. The human-dog bond started thousands of years ago. The higher prevalence of dog ownership around the world, especially in households including children along with the growing number of people studying dogs most likely explain the growing literature focusing on child-dog interactions. We review the potential effects of child-dog interactions on the physical, mental, and social wellbeing of both species. A scoping search of the SCOPUS database found several hundred documents meeting selection criteria. It allowed us to define the numerous ways in which children and dogs can interact, be it neutral (e.g., sharing a common area), positive (e.g., petting), or negative (e.g., biting). Then, we found evidence for an association between interacting with dogs during childhood and an array of health and mental benefits like stress relief and the development of empathy. Walking a dog and playing with one are perfect physical activity opportunities. Additionally, interacting with a dog can help lower stress and may have a role in the development of empathy. Nonetheless, a number of detrimental outcomes have also been identified in both humans and dogs. Children are the most at-risk population regarding dog bites and dog-borne zoonoses, which may lead to a subsequent fear of dogs or even death. Moreover, pet bereavement is generally inevitable when living with a canine companion and should not be trivialized. In terms of dogs, children sometimes take part in caretaking behaviors toward them which include going on walks. They are opportunities for dogs to relieve themselves outside, but also to exercise and socialize. In contrast, a lack of physical activity can lead to the onset of obesity. Dogs may present greater levels of stress when in the presence of children. Finally, the welfare of assistance, therapy, and free-roaming dogs remains underexplored. Overall, the study of the effects, positive as well as negative, on both species still requires further development. We call for more longitudinal studies and hope for cross-cultural research in the future in order to better understand the impact child-dog interactions might have.

Here we review and describe a set of research priorities to meet present and future challenges posed to farmed animal production that build on progress, successes and resources from the Functional Annotation of ANimal Genomes (FAANG) project.

Today's city needs more than ever methodological devices that ensure a specific urbanism, in keeping with the complexity of relationships that occur in the urban space. Networks or systems of diverse nature must be activated to achieve a certain success of the city, even more so in its fragile central fabrics. The study is focused on the historic neighborhoods of the city of Jaén (Spain), which have a high vulnerability index. The aim is to establish a strategy to revitalize their urban and social capital and improve their articulation with the rest of the urban and territorial structure. A methodological proposal for the analysis of vulnerability factors and an urban and cartographic analysis of the public space is addressed through an interweaving of a triple network: environmental, social, and urban. For this purpose, the configuration of this overlapping network of analysis and formulation of criteria is presented, which considers the urban multiplicity and promotes new dynamics for the integrated urban regeneration of the area and for the activation of public and collective urban spaces.

Mild traumatic brain injury (mTBI) is the most common brain injury, seen in sports, falls, vehicle, or workplace injuries. Concussion is the most common type of mTBI. Assessment of impairments from concussion are evolving, with oculomotor testing suggested as a key component in a multi-modality diagnostic protocol. The aim of this study was to evaluate the reliability of one eye-tracking system, the EyeGuide Focus. Seventy-five healthy adolescent and adult participants (adolescents: n=28; female=11, male=17, mean age 16.5 ± 1.4 years; adults n=47; female=22; male=25, mean age 26.7 ± 7.0 years) completed three repetitions of the EyeGuide Focus within the one session. Intraclass correlation coefficient (ICC) analysis showed the EyeGuide Focus had overall good reliability (ICC 0.79, 95%CI: 0.70, 0.86). However, a familiarization effect showing improvements in subsequent trials was noticeable in both cohorts (p<0.001) with adolescent participants showing greater familiarisation effects than adults. No differences were observed between sexes (p=0.69). Overall, the EyeGuide Focus was found to be reliable, but the observation of familiarization effects suggests that a standardized protocol of a minimum of three trials be employed, similar to other eye-movement testing applications.

With the global increase of photovoltaic (PV) modules deployment in recent years, the need to explore and realize their reported failure mechanisms has become crucial. Despite PV modules being considered reliable devices, failures and extreme degradations often occur. Some degradations and failures can be minor and cause no critical harm if within the expected range. Others, may start mildly and then deteriorate faster to become catastrophic, especially in harsh environments. This paper conducts a state-of-the-art literature review to scan PV failures, types, and their root cause based on PV’s constructed components (from protective glass to junction-box). It outlines the hazardous consequences beyond PV module failures, describing what harm they can bring to the PV system. As we delve into the literature, it becomes clear that every component is vulnerable to certain types of failures; some can deteriorate within themselves, and others infect further PV components resulting in emerging more severe failures. In the end, the review briefly summarises PV failure detection techniques, emphasising electrical characterization techniques, and disclosing the need to engage more electrical parameters. Most importantly, this review can prepare the stage for the PV research community to identify the most prevalent degradation processes. This, in turn, encourages researchers to investigate them throughout modelling and experimental studies to forecast them at the early onset in order to protect the PV systems from hazardous malfunctions.

The presented study demonstrates the bi-sensor approach suitable for rapid and precise up-to-date mapping of forest canopy gaps for the larger spatial extent. The approach makes use of UAV RGB images on smaller areas for highly precise forest canopy mask creation. Sentinel-2 was used as a scaling platform for transferring information from UAV to a wider spatial extent. The various approaches of the improvement of the predictive performance were examined: (I) the highest R2 of the single satellite index was up to 0.57, (II) the highest R2 using multiple features obtained from the single date, S-2 image was 0.624 and, (III) the highest R2 on the multi-temporal set of S-2 images, was 0.697. Satellite indices such as ARVI, IPVI, NDI45, PSSRa, MCARI, CI, RI, and NDTI were the dominant predictors in most of the ML algorithms. The more complex ML algorithms such as SVM, Random Forest, GBM, XGBoost, and Catboost that provided the best performance on the training set exhibited weaker generalization capabilities. Therefore, a simpler and more robust Elastic Net algorithm was chosen for the final map creation.

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.

A substantial amount of phosphorus (P) in soil is not readily available for plant uptake. Certain species may enhance P availability from poorly soluble P forms. This research aimed to compare the P solubilization capacity of the soil of two Lupine species, L. albus, and L. angustifolius, with a control crop of oats (Avena strigosa L.). Plants were planted in pots in four soils with varying texture, organic matter content, acidity, and P availability. Phosphorus solubilization capacity was assessed on variations of P availability (PBray1) at four points in time, comparing soils with lupine to oat-containing soils and their baseline values. At harvest, measurements of plant shoot biomass included their shoot dry weight and some nutrient concentrations such as P, nitrogen (N), manganese (Mn), and lupine nitrogen fixation. Compared to soils containing oats, lupine soils significantly increased PBray1 concentrations; increments ranged from 0.9 to 5.4 mg kg-1, depending on species, sampling time, and soil type. Lupine-induced soil acidification did not fully explain this P increase., As a proxy measurement of organic acid exudation, Manganese concentration was high in both lupine species' shoot biomass; however, these legumes had divergent Mn accumulation responses to soil acidity and P availability. Nitrogen fixed quantity varied with Lupine species (105-240 mg pot-1) and soil type (60-240 mg pot-1). Lupinus albus had a higher ability to mobilize non-labile P and provide N through biological N fixation (BNF), positioning it as a suitable crop for diversifying Uruguay's agricultural crop rotation systems.

Currently, there is a tenacious need to find new ways to purify water by eliminating bacterial biofilms, textile dyes, and toxic water pollutants. These contaminants pose significant risks to both human health and the environment. To address this issue, in this study, we have developed an eco-friendly approach that involves synthesizing Cobalt-doped Cerium Iron Oxide (CCIO) nanocomposite (NC) using an aqueous extract of Gossypium arboreum L. stalks. The resulting nanoparticles can be used to effectively purify water and tackle the challenges associated with these harmful pollutants. Nanoparticles excel in water pollutant removal by providing high surface area for efficient adsorption, versatile design for simultaneous removal of multiple contaminants, catalytic properties for organic pollutant degradation, and magnetic features for easy separation, offering cost-effective and sustainable water treatment solutions. CCIO nanocomposite has been synthesized by green co-precipitation method due to biomolecules and co-enzymes present in the aqueous extract of Gossypium arboreum L. stalk; a single-step procedure completed in 5 h reaction time. Further, the synthesis of nanocomposites was confirmed by various characterization techniques such as Fourier-transform infrared (FT-IR) spectroscopy, X-ray diffraction (XRD), Field emission scanning electron microscopy (FE-SEM), Transmission electron microscopy (TEM), Thermogravimetric analysis (TGA), Dynamic light scattering (DLS), and Energy Dispersive X-Ray (EDX). CCIO NCs were discovered to have a spherical shape and an average size of 40 nm. Based on DLS zeta potential analysis, CCIO NCs were found to be anionic. Also, CCIO NCs showed significant antimicrobial and antioxidant activity. Overall, considering the physical and chemical properties, the application of CCIO NCs in the adsorption of various dyes (~91 %) and water pollutants (chromium = ~ 60 %) has been considered since they exhibit great adsorption capacity owing to their microporous structure which can be a step forward in water purification.

High Brassicaceae consumption reduces the risk of developing several cancer types, probably due to their glucosinolate amount. Extracts from Sinapis nigra L. and Sinapis alba L. have been obtained from leaves and seeds under different conditions using ethanol/water mixtures because well accepted by food industry. The EtOH/H2O 8:2 mixture gives better yields in glucosinolate amounts from grinded seeds, mainly sinalbin in S. alba and sinigrin in S. nigra. The highest antiproliferative activity in both non-tumour and tumour cell lines was induced by S. alba seeds extract. To evaluate whether Sinapis spp effect was only due to glucosinolate content or it was influenced by the extracts’ complexity, cells were treated with extracts or glucosinolates, in the presence of myrosinase. Pure sinigrin did not modify cell proliferation, while pure sinalbin was less effective than the extract. The addition of myrosinase increased the antiproliferative effects of the S. nigra extract and sinigrin. Antiproliferative activity was correlated to MAPKs modulation, which was cell and extract-dependent. Cell-cycle analysis evidenced a proapoptotic effect of S. alba on both tumour cell lines and of S. nigra only on HCT 116. Both extracts showed good antimicrobial activity in disc diffusion tests and on ready-to-eat fresh salad. These results underline the potential effects of Sinapis spp in chemoprevention and food preservation.

Rett Syndrome (RTT) is a severe neurodevelopmental disorder predominately diagnosed in females and primarily caused by pathogenic variants in the X-linked gene Methyl-CpG Binding Protein 2 (MECP2). Most often, the disease causing MECP2 allele resides on the paternal X chromosome while a healthy copy is maintained on the maternal X chromosome with inactivation (XCI) resulting in mosaic expression of one allele in each cell. Preferential inactivation of the paternal X chromosome is theorized to result in reduced disease severity; however, establishing such a correlation is complicated by known MECP2 genotype effects and an age dependent increase in severity. To mitigate these confounding factors, we developed an age- and genotype-normalized measure of RTT severity by modeling longitudinal data collected in the US Rett Syndrome Natural History Study. This model accurately reflected individual increase in severity with age and preserved group-level genotype specific differences in severity allowing for the creation of a normalized clinical severity score. Applying this normalized score to a RTT XCI dataset revealed that XCI influence on disease severity depends on MECP2 genotype with a correlation between XCI and severity observed only in individuals with MECP2 variants associated with increased clinical severity. This normalized measure of RTT severity provides the opportunity for future discovery of additional factors contributing to disease severity that may be masked by age and genotype effects.

The National Occupational Competency Profile (NOCP) – the competency framework for paramedics in Canada – is presently undergoing revision. Since the NOCP was published in 2011, paramedic practice, healthcare and society have changed dramatically. To inform the revision, we sought to identify emerging concepts in the literature that would inform the development of competencies for paramedics. We conducted a restricted literature review and content analysis of all published and grey literature pertaining to or informing Canadian paramedicine from 2011 to 2022. Three authors performed a title and abstract, and full-text review to identify and label concepts informed by existing findings. A total of 302 articles were categorized into eleven emerging concepts related to competencies: Inclusion, Diversity, Equity, and Accessibility (IDEA) in paramedicine; Social responsiveness, justice, equity and access; Anti-racism; Healthy Professionals; Evidence Informed Practice and Systems; Complex Adaptive Systems; Learning Environment; Virtual Care; Clinical Reasoning; Adaptive Expertise; and Planetary Health. This review identified emerging concepts to inform the development of the 2023 National Occupational Standard for Paramedics (NOSP). These concepts will inform data analysis, development group discussions, and competency identification.

Supernova remnants (SNRs) are an integral part in studying the properties of the Galaxy and its interstellar medium. For the current work, we explore the relation between the observed radio luminosities of SNRs and the physical properties of those SNRs. The physical properties of 54 SNRs are derived from their observed X-ray spectra. Then the observed radio emission is compared to predicted radio emission using the analytic model of . We find the model can be improved significantly by including an interstellar medium density dependence in the efficiency of particle acceleration and magnetic field amplification.

Snowpack loss in midlatitude mountains is ubiquitously projected by Earth system models, though the magnitudes, persistence and time horizons of decline vary. Using daily downscaled hydroclimate and snow projections we examine changes in snow seasonality across the U.S. Pacific Southwest region during a simulated severe 20-year dry spell in the 21st century (2051–2070) developed as part of the 4th California Climate Change Assessment to provide a "stress test" for water resources. Across California’s mountains, substantial declines (30–100% loss) in median peak annual snow water equivalent accompany changes in snow seasonality throughout the region compared to the historic period. We find 80% of historic seasonal snowpacks transition to ephemeral conditions. Subsetting empirical-statistical wildfire projections for California by snow seasonality transition regions indicates a two-to-four-fold increase in burned area, consistent with recent observations of high elevation wildfires following extended drought conditions. By analyzing six of the major California snow-fed river systems we demonstrate snowpack reductions and seasonality transitions result in concomitant declines in annual runoff (47-58% of historic values). The negative impacts to statewide water supply reliability by the projected dry spell will likely be magnified by changes in snowpack seasonality and increased wildfire activity.

Spider toxin SNX-482 is a cysteine-rich peptide that interferes with calcium channel activity by binding to voltage-sensing domains of CaV2.3 subtype. Two general binding mechanisms are present in nature: direct binding from the aqueous phase or through lateral diffusion from the membrane, the so-called reduction in dimensionality mechanism. In this work, via coarse-grained and atomistic molecular dynamics simulations, we have systematically studied the spontaneous partitioning of SNX-482 with membranes of different anionic compositions and explored via diffusional analysis both binding mechanisms. Our simulations revealed a conserved protein patch that inserts within the membrane, a preference for binding towards partially negatively charged membranes, and that electrostatics drives membrane binding. Finally, diffusivity calculations showed that the toxin diffusion along the membrane plane is an order of magnitude slower than the aqueous phase suggesting that the critical factor in determin-ing the SNX-482-CaV2.3 binding mechanism is the affinity between the membrane and SNX-482

The Upper Hunter Valley is a major coal mining area containing approximately 40% of the currently identified total coal reserves in New South Wales (NSW), Australia. Due to the ongoing increase of mining activities, PM10 (air-borne particle with an aerodynamic diameter less than 10 micrometres) pollution has become a major air quality concern in local communities. This paper summarises the spatial and temporal variability modes of PM10 pollution in the region, based on long-term multi-site monitoring data and the application of the rotated principal component analysis (RPCA) and wavelet analysis techniques. RPCA identified two distinct air quality clusters/subregions in the valley, one in the west/northwest, the other in the southeast. Wavelet analysis revealed the annual cycle to be most persistent temporal mode of PM10 variability in both subregions, with intermittent signals observed at time scales of around 120, 30~90 and under 30 days. How these variation modes are related to the effects of local PM10 emissions and the influence of meteorology at different time scales deserves further attention in future work. The findings will be used in air quality reporting and forecasting in NSW. The methodology and results can also be useful for air quality research in similar regions elsewhere.

We present synthetic experiments of lactic acid (LA) polycondensation to produce poly(lactic acid) (PLA), as well as kinetic modeling calculations that capture the polymer molecular weight increase with time, given the initial concentrations. Tin-octoate-catalyzed polycondensation of (D,L)- or L-lactic acid, was carried out in pre-dried toluene after azeotropic dehydration for 48-120 hours at 130-137 °C. The polymerization was optimized by varying lactic acid and catalyst concentrations as well as the temperature. Gel Permeation Chromatography was used to experimentally follow the evolution of molecular weights and the products were characterized by NMR, TGA, DSC and IR. Under optimal conditions, PLLA with weight-average molecular weight (Mw) of 161 kDa could be obtained. The rate equations that describe polycondensation kinetics were recast in a condensed form that allowed very fast numerical solution and calculation of the number-average molecular weight with time. Deviations with respect to the experiment were minimized in a least-squares fashion, to determine rate constants. The optimized kinetics parameters are shown to reproduce the experimental data accurately

New composite with core-shell structure based on magnesium hydride and finely dispersed aluminum powder with aluminum oxide shell was mechanically synthesized. We used magnesium chips to produce magnesium hydride and aluminum wire after exploitation to produce nano-sized aluminum powder. The beginning of the hydrogen release from composite occurred at the temperature of 117°C. The maximum desorption temperature from the MgH₂-EEWAl composite (10 wt.%) is 336°C compared to pure magnesium hydride – 417°C. The mass content of hydrogen in the composite is 5.5 wt.%. The positive effect of aluminum powder produced by the electric explosion of wires method on reducing the activation energy of desorption was demonstrated. Calculations showed that the activation energy of desorption for the composite is 106±1 kJ/mol, compared with pure magnesium hydride, whose activation energy was 155±2 kJ/mol. The results obtained make it possible to expand the possibility of using magnesium and aluminum waste for hydrogen energy.

A large number of smart devices (things) are being deployed with the swift development of Inter- net of Things (IOT). These devices, owned by different organizations, have a wide variety of services to offer over the web. During a natural disaster or emergency (i.e., a situation), for example, relevant IOT services can be found and put to use. However, appropriate service matching methods are required to find the relevant services. Organizations that manage situation responses and organizations that provide IOT services are likely to be independent of each other, and therefore it is difficult for them to adopt a common ontological model to facilitate the service matching. Moreover, there exists a large conceptual gap between the domain of discourse for situations and the domain of discourse for services, which cannot be adequately bridged by existing techniques. In this paper, we address these issues and propose a new method, WikiServe, to identify IOT services that are functionally relevant to a given situation. Using concepts (terms) from situation and service descriptions, WikiServe employs Wikipedia as a knowledge source to bridge the conceptual gap between situation and service descriptions and match functionally relevant IOT services for a situation. It uses situation terms to retrieve situation related articles from Wikipedia. Then it creates a ranked list of services for the situation using the weighted occurrences of service terms in weighted situation articles. WikiServe performs better than a commonly used baseline method in terms of Precision, Recall and F measure for service matching.

Osteoarthritis (OA) has become one of the most common disabilities among elders, especially in female. Obesity and mechanical injury causing OA are attributed to joint loading, cartilage disintegration, bone loss and inflammation as well. Several strategies used for treatment OA including non-pharmacological and pharmacological. Fucoidan possesses several bioactivities such as antitumor, antiviral, anticoagulation, anti-obesity, and immunomodulation. This study aims to investigate the effect of fucoidan in surgery-induced OA on diet-induced obesity rats. OA was induced by anterior cruciate ligament transection and partial medial meniscectomy (ACLT+MMx). Male SD rats were fed high-fat diet (HFD) for 4 weeks to induce obesity before ACLT+MMx to induce OA. OA rats were administered with intragastric water or fucoidan in three different concentrations (32 mg/kg, 64 mg/kg, and 320 mg/kg) after the surgeries for 40 days with HFD. We observed that the swelling in knee joint was alleviated and hind paw weight distribution was rectified after feeding fucoidan, with no significant effect on weight gain and feed intake. Fucoidan administration indicated no significant variation on HDL-Cholesterol level, but reduced plasma triglycerides and LDL-Cholesterol level. In addition, weight-bearing tests showed improvement in the fucoidan-treated group. Our results suggested that fucoidan may improve meniscal/ligamentous injury and obesity-induced OA.

Introduction: As the paramedic profession continues to grow and evolve, a shift from reactive to holistic patient care models is required. As the first and often the only point of medical contact for many patients from marginalized and under-served populations, the paramedic role, and its potential future implications in caring for these patients needs to be explored. Aim: The objective of this scoping review was to explore the paramedic's role in caring for people who use illicit drugs. Methods: A scoping review of English language literature published since 2002 was conducted using CINAHL, MEDLINE, EMBASE, and Google Scholar. We used a previously published paramedic search term filter for sensitivity combined with search terms related to drug-related substance use and addiction. Studies were selected based on relevance to the research question. Results: A total of 104 peer-reviewed and 14 grey literature articles were selected for inclusion. The main finding of this scoping review is the notable lack of evidence base surrounding the contemporary paramedic role in the care provision of people who use drugs (PWUD). The results highlight high rates of mortality following a paramedic-attended drug poisoning event, presenting a unique opportunity for paramedics to intervene in meaningful ways that extend past traditional drug poisoning response. Conclusions: The interface between the community of PWUD and the paramedic may be a highly influential encounter during a patient's journey through the healthcare system. The evolving role of the paramedic in this encounter requires focused study and should be viewed as a research priority in response to the ongoing drug poisoning crisis.

Eicheon properties are discussed. It is shown that the eicheon surface allows setting a boundary condition for the vacuum polarization and obtaining a solution describing the dark matter tail in the Milky Way. That is, the dark matter in the Milky Way is explained as the F-type of vacuum polarization, which could be treated as dark radiation. The model presented is spherically symmetric, but a surface density of a baryonic galaxy disk is taken into account approximately by smearing the disk over a sphere. This allows the reproduction of the large distance shape of the Milky Way rotational curve. Andromeda's rotational curves are also discussed.

Globally, bridges fail mostly due to hydrological causes such as scour or flooding. Therefore, under a hydrological approach, this study proposes a methodology that contributes to prioritize the intervention of bridges to prevent their collapse. Through an exhaustive literature review, an evaluation matrix subdivided into 4 dimensions was developed and a total of 18 evaluation parameters were considered, distributed as follows: 4 environmental, 6 technical, 4 social and 4 economic. This matrix was applied to eight bridges with a history of hydrological problems in the same river and validated through semi-structured interviews with specialists. Data were collected through field visits, journalistic information, review of the gauged basin historical hydrological flow rates and consultations with the population. Then, the modeling, which considered the influence of gullies that discharge additional flow, was carried out using HEC-HMS and HEC-RAS and subsequently calibrated. The application of the matrix revealed that five bridges have a high vulnerability, and three bridges have a medium vulnerability. The multidimensional approach can be adapted for studies of other riverine bridges.

Understanding the evolutionary role of environmentally-induced phenotypic variation (i.e., environmental plasticity) is an important issue in developmental evolution. One of the major physiological responses to environmental changes is cellular stress, which is counteracted by a generic stress reaction that detoxifies the cell, refolds proteins, and repairs DNA damage. In this paper, we elaborate on a previous finding suggesting that the cell differentiation cascade of human decidual stromal cells, a cell type critical for embryo implantation and the maintenance of pregnancy, evolved from a cellular stress reaction. We hypothesize that the stress reaction in these cells was elicited ancestrally through the inflammation caused by embryo attachment and invasion. We describe a model, Stress-Induced Evolutionary Innovation (SIEI), whereby ancestral stress reactions and their corresponding pathways can be transformed into novel structural components of body plans, such as new cell types. After reviewing similarities and differences between SIEI and the “plasticity first hypothesis” (PFH) of evolution, we argue that SIEI is a distinct form of plasticity-based evolutionary change because it leads to the origin of novel structures rather than the adaptive transformation of a pre-existing character.

Humans may be exposed to microbial pathogens at recreational beaches via environmental sources, such as water, sand, and aerosols. Although infectious disease risk from exposure to waterborne pathogens has been an active area of research for decades, sand is a relatively unexplored reservoir of pathogens and fecal indicator bacteria (FIB). Beach sand and water habitats provide unique advantages and challenges to pathogen introduction, growth, and persistence, as well as continuous exchange between habitats. Models of FIB and pathogen fate and transport in sandy beach habitats can help predict the risk of infectious disease from recreational water use, but filling knowledge gaps such as decay rates and potential for microbial growth in beach habitats is necessary for accurate modeling. Climatic variability, whether natural or anthropogenically-induced, adds complexity to predictive modeling, but may increase human exposure to waterborne pathogens via extreme weather events, warming of water bodies and sea level rise in many regions. The popularity of human recreational beach activities, combined with predicted climate change scenarios, could amplify the risk of human exposure to pathogens and related illnesses. Other global change trends such as increased population growth and urbanization are expected to exacerbate contamination events and the predicted impacts of increasing levels of waterborne pathogens on human health. Such changes will alter microbial population dynamics in beach habitats, and will consequently affect the assumptions and relationships used in population models and quantitative microbial risk assessment (QMRA). Here, we discuss the literature on microbial population and transport dynamics in sand-water continuum habitats at beaches, how these dynamics can be modeled, and how climate change and other anthropogenic influences (e.g., land use, urbanization) should be considered when using and developing more holistic, beachshed-based models.

During the bioassay, on leaf sections of the A. roylei species, a significantly higher number of T. tabaci females was recorded compared to the cv. Tęcza of the A. cepa species and the cv. Kroll of the A. fistulosum species, in each observation period. Significantly more thrips settled on cv. Kroll compared to Alibaba and Bila. Regarding the results obtained on A. cepa, significantly fewer females were found on cv. Bila compared to cv. Tęcza. Opposite results were observed in a combination of cvs. Tęcza - Alibaba, where significantly more insects settled on leaves of cv. Alibaba. Statistically significant differences of cultivars/species were found in the number of hatched larvae on the leaves of the tested cultivars/species of onion. The significantly lowest number of larvae hatched from eggs laid on A. roylei compared to A. fistulosum and cultivars of A. cepa, except for Bila.

Violence against paramedics has been described as a ‘serious public health problem’ but one that remains ‘vastly underreported’, owing to an organizational culture that stigmatizes reporting – hindering efforts at risk mitigation in addition to creating a gap in research. Leveraging a novel reporting process developed after extensive stakeholder consultation and embedded within the electronic patient care record, our objective was to provide a descriptive profile of violence against paramedics in a single paramedic service in Ontario, Canada. Between February 1, 2021, through January 31, 2023, a total of 374 paramedics in Peel Region (48% of the workforce) generated 941 violence reports, of which 40% documented physical (n=364) or sexual (n=19) assault. The violence was typically perpetrated by patients (78%) and primarily took place at the scene of the 9-1-1 call (47%); however, violent behavior frequently persisted or recurred while in transit to hospital and after arrival. Collectively, mental health, alcohol, or drug use were listed as contributing circumstances in 83% of violence reports. In all, 81 paramedics were physically harmed because of an assault. On average, our data correspond to a paramedic filing a violence report every 18 hours, being physically assaulted every 46 hours, and injured every 9 days.

A U.S. government health agency conducted epidemiological studies to evaluate whether exposures to drinking water contaminated with volatile organic compounds at U.S. Marine Corps Base Camp Lejeune, North Carolina, were associated with increased health risks to children and adults. These health studies required knowledge of contaminant concentrations in drinking water—at monthly intervals—delivered to family housing, barracks, and other facilities within the study area. Because concentration data were limited or unavailable during much of the period of contamination (1950s–1985), the historical reconstruction process was used to quantify estimates of monthly mean contaminant-specific concentrations. This paper integrates many efforts, reports, and papers into a synthesis of the overall approach to, and results from, a drinking-water historical reconstruction study. Results show that at the Tarawa Terrace water treatment plant (WTP) reconstructed (simulated) tetrachloroethylene (PCE) concentrations reached a maximum monthly average value of 183 micrograms per liter (ug/L) compared to a one-time maximum measured value of 215 ug/L and exceeded the U.S. Environmental Protection Agency’s current maximum contaminant level (MCL) of 5 ug/L during the period November 1957–February 1987. At the Hadnot Point WTP, reconstructed trichloroethylene (TCE) concentrations reached a maximum monthly average value of 783 ug/L compared to a one-time maximum measured value of 1,400 ug/L during the period August 1953–December 1984. The Hadnot Point WTP also provided contaminated drinking water to the Holcomb Boulevard housing area continuously prior to June 1972, when the Holcomb Boulevard WTP came on line (maximum reconstructed TCE concentration of 32 ug/L) and intermittently during the period June 1972–February 1985 (maximum reconstructed TCE concentration of 66 ug/L). Applying the historical reconstruction process to quantify contaminant-specific monthly drinking-water concentrations is advantageous for epidemiological studies when compared to using the classical exposed versus unexposed approach.

The cryopreservation of gametes and embryos is an important element of biodiversity conservation. One species in need of conservation is the honey bee Apis mellifera L. Changing environmental factors, especially the anthropogenic factor, have led to a reduction in the numbers of this insect species. In this study, we provide an example of the creation of a biobank of honey bee drone sperm. For sperm cryopreservation, drones of the most common subspecies of honey bees common in Russia were selected. These were the dark forest bee, Apis mellifera mellifera from the Republic of Bashkortostan, with three subspecies (A. m. carnica, A. m. carpatica, and A. m. caucasica) from the southern regions of Russia, as well as two breeding stocks, the Far Eastern bee and Prioksky bee. For subspecies identification, morphometric and genetic methods were used. The subspecies of the studied samples were confirmed by the analysis of the tRNAleu-COII locus of mitochondrial DNA and nine microsatellite markers of nuclear DNA. It was shown that bees of the Prioksky breeding stock belong to the subspecies A. m. caucasica based on phylogenetic analysis, and the Far Eastern breeding stock is a stable hybrid, descending on the maternal line from the evolutionary lineage C or O. The results of the morphometric analysis are consistent with the results of the genetic analysis. For the cryopreservation of sperm, we used a honey diluent. As a result, the viability of frozen–thawed sperm decreased by 20.3% compared to fresh sperm, and overall motility decreased by 25-fold. The measurement of the sperm concentration in the spermatheca of artificially inseminated queens showed that it varied from 0.22 to 4.4 million/μL. Therefore, the use of honey in sperm cryopreservation has great potential.

In this paper, comprehensive analysis of combined effect of major influencing parameters on heat transfer in the single U-tube BHE (sBHE) and double U-tube BHE (dBHE) with two independent circuits was performed by using validated numerical heat transfer model. Geometrical parameters, such as shank spacing (with maximum, average and minimum values) and borehole diameter (large, medium and small borehole sizes) and borehole depth (shallow, average and deep borehole depths) as well as thermal conductivity of soil and grout which ranges from minimum to high value were considered. The combined impact of these parameters was included under four major cases: 1) combined effect of borehole depth, borehole size and shank spacing; 2) combined effect of borehole depth, and soil and grout thermal conductivity; 3) combined effect of soil and grout thermal conductivity and borehole size; and 4) combined effect of soil thermal conductivity, borehole size and shank spacing. Each of these major cases has nine different design options of both sBHE and dBHE. Series of results of heat transfer per unit borehole depth were generated for all the considered various cases. With the given parameters, the BHE case that provides highest heat transfer among the various cases of sBHE and dBHE were obtained.

Artisanal and small-scale gold mining (ASGM) has been an important source of income for communities in the Madre de Dios River Basin in Peru for hundreds of years. However, in recent decades, the scale of ASGM activities in the region has increased dramatically, and exposures to a variety of occupational and environmental hazards related to ASGM, including mercury, are becoming more widespread. The aims of our study were to: (1) examine patterns in the total hair mercury level of human participants in several communities in the region and compare these results to the 2.2 µg/g total hair mercury level equivalent to the World Health Organization (WHO) Expert Committee of Food Additives (JECFA)’s Provisional Tolerable Weekly Intake (PTWI); and (2), to measure the mercury levels of paco (Piaractus brachypomus) fish raised in local aquaculture ponds, in order to compare these levels to the EPA Fish Tissue Residue Criterion of 0.3 µg Hg/g fish (wet weight). We collected hair samples from 80 participants in four communities (one control and three where ASGM activities occurred) in the region, and collected 111 samples from fish raised in 24 local aquaculture farms. We then analyzed the samples for total mercury. Total mercury levels in hair were statistically significantly higher in the mining communities than in the control community, and increased with increasing distance away from the Madre de Dios headwaters (as the crow flies), did not differ by sex, and frequently exceeded the reference level. Regression analyses indicated that higher hair mercury levels were associated with residence in ASGM communities. The analysis of paco fish samples found no samples that exceeded the EPA tissue residue criterion. Collectively, these results align with other recent studies showing that ASGM activities are associated with elevated human mercury exposure. The fish farmed through the relatively new process of aquaculture in ASGM areas appeared to have little potential to contribute to human mercury exposure. More research is needed on human health risks associated with ASGM to discern occupational, residential, and nutritional exposure, especially through tracking temporal changes in mercury levels as fish ponds age, and assessing levels in different farmed fish species. Additionally, research is needed to definitively determine that elevated mercury levels in humans and fish result from the elemental mercury from mining, rather than from a different source, such as the mercury released from soil erosion during deforestation events from mining or other activities.

Transportation systems through the ages have seen drastic evolutions in terms of transportation methods, speed of transport, infrastructure, technology, connectivity, influence on the environment, and accessibility. The massive transformation seen in the transportation sector has been fueled by the industrial revolutions which have continued expansion and progress into the fourth industrial revolution. However, the methodologies of data collection and processing used by the many drivers of this progress differ. The significance of standardized data and its mode of collection cannot be overstated as it has a major impact on the process outcomes. In order to achieve a better understanding of the impact of this, this study methodically reviewed the literature on the subject of the data collection and processing mechanism of 4IR technologies in the context of the transport industry with an emphasis on the areas of accomplishment of several studies and drawing attention to their limitations. Although the industry has advanced significantly as a result of the adoption and application of various research studies in this field, considerable focus needs to be placed in the areas of standardized data collection and computational approaches, which will ultimately assist in achieving various benefits in the transportation industry.

Competency frameworks are developed for a variety of purposes, including describing professional practice and informing education and assessment frameworks. Despite the volume of competency frameworks developed in the healthcare professions, guidance remains unclear and is inconsistently adhered to (perhaps in part due to a lack of organising frameworks), there is variability in methodological choices, inconsistently reported outputs, and a lack of evaluation of frameworks. As such, we proposed the need for improved guidance. In this paper we outline a six-step model for developing competency framework that is designed to address some of these shortcomings. The six-steps comprise [1] identifying purpose, intended uses, scope, and stakeholders; [2] theoretically informed ways of identifying the contexts of complex, ‘real-world’ professional practice, which includes [3] aligned methods and means by which practice can be explored; [4] the identification and specification of competencies required for professional practice, [5] how to report the process and outputs of identifying such competencies, and [6] built-in strategies to continuously evaluate, update and maintain competency framework development processes and outputs. The model synthesizes and organizes existing guidance and literature, and furthers this existing guidance by highlighting the need for a theoretically-informed approach to describing and exploring practice that is appropriate, as well as offering guidance for developers on reporting the development process and outputs, and planning for the ongoing maintenance of frameworks.

Industrial hemp (Cannabis sativa L.) is an attractive candidate for sustainable pest management due to its abundance of bioactive compounds with potential pesticidal properties. Solvent choice has a significant impact on the extraction efficiency of bioactive compounds. Deep Eutectic Solvents (DESs) are gaining popularity in extraction because they are safe and environmentally friendly, making them viable alternatives to organic solvents (OSs). This research first compared the extraction efficiency of OSs on the extraction of phytochemicals from the infloresences of two hemp varieties, Citrus and Cherry Dwarf. Inflorescences were extracted using three OSs, ethanol, ethyl acetate, and hexane. The highest level of cannabidiol (CBD; 0.69%) was extracted from Cherry Dwarf using ethanol while the level of delta-9 tetrahydrocannabinol THC (0.19%) was essentially the same in both. Therefore, Cherry Dwarf was selected to compare the extraction efficiency of DESs to the OSs. The DESs were choline chloride/ethylene glycol, citric acid/ethylene glycol, menthol/lauric acid, choline chloride/urea and choline chloride/glycerol. In the targeted analysis, choline chloride/ethylene glycol extracted the highest amount of CBD (0.87%) followed by choline chloride/urea (0.78%). As some DESs outperformed ethanol, the popular solvent for extracting cannabinoids, DESs are viable candidates to replace organic solvents.

Ageing is associated with a decline in both Nrf2 activity and DNA repair efficiency, leading to the accumulation of DNA damage and an increased risk of cancer. Understanding the mechanisms behind the increased level of damaged DNA during ageing is crucial for developing interventions to mitigate age-related cancer risk and improve overall health in older individuals. (Poly)phenols are plant-derived bioactive compounds that undergo metabolism into simpler phenolic catabolites following ingestion. While these compounds have been associated with various health benefits, further analysis of their bioavailable catabolites is necessary. To this end, four phenolic catabolites derived from colonic microbiota were investigated for their ability to reduce DNA damage in response to oxidative challenge and modulate the Nrf2-Antixoidant Response Element pathway. Normal and adenocarcinoma colonocyte cell lines (CCD 841 CoN, & HT29 respectively) were exposed to sub cytotoxic concentrations (>10 µM,) of hydroxylated (4-hydroxybenzoic acid, 3-(3’-hydroxyphenyl) propionic acid) and non-hydroxylated (benzoic acid or 3-phenylpropionic acid) phenolic acids. Using the COMET assay, each catabolite demonstrated significant (p<0.001) geno-protective activity, albeit with varying potency. They also significantly modulated expression of key genes in the Nrf2-ARE pathway, including Nrf2, Heme oxygenase-1 (HO-1), and NAD(P)H dehydrogenase quinone 1 (NQO1). Hydroxylation of the phenolic acids appeared to have a limited effect with respect to bioactivity. Overall, the colon derived phenolic metabolites, when assessed at physiologically relevant concentrations, reduced DNA damage in both normal and adenocarcinoma colonic cells in response to oxidative challenge, mediated – at least in part via upregulation of the Nrf2-ARE pathway.

Nowadays, the identification and characterization of grapevine cultivars resilient to climate and water stress while preserving quality traits is crucial for the wine industry. Therefore, the objective of this work was to characterize according to their aromatic potential 9 white and 6 red minority cultivars recently recovered from Castilla-La Mancha region (Spain), subjected at two different water deficit regimes: rainfed, with subsistence irrigation, and irrigated. For this, the varietal aromatic potential index (IPAv) and the detailed aromatic composition were analyzed by HS-SBSE-GC/MS, in extracts of two different ph. For IPAv values, red varieties did not show a clear trend with respect to irrigation. However, in white minority varieties, higher values were obtained under irrigation conditions. Thus, a clear differentiation of the minority varieties in comparison to the references was observed, primarily attributed to the content of esters and acids, in both white and red varieties. A notable contrast was observed at different pH, indicating a greater extractability of certain compounds like linalool, under more acidic conditions. This suggests that some recovered minority cultivars could be promising for cultivation in semi-arid regions with limited water, contributing to the wine sector sustainability in the future.

Within the field of guilt and shame, two competing perspectives have been advanced. The first, the social-adaptive perspective, proposes that guilt is an inherently adaptive emotion and shame is an inherently maladaptive emotion; thus, those interested in moral character development and psychopathology should work to increase an individual’s guilt-proneness and decrease an individual’s shame-proneness. The functionalist perspective, in contrast, argues that both guilt and shame can serve a person adaptively or maladaptively—depending on the situational appropriateness, duration, intensity, and so forth. This paper reviews the research conducted supporting both positions, critiques some issues with the most widely used guilt- and shame-proneness measure in the social-adaptive research (the TOSCA), and discusses the differences in results found when assessing guilt and shame at the state versus trait level. The conclusion drawn is that although there is broad support for the functionalist perspective across a wide variety of state and trait guilt/shame studies, the functionalist perspective does not yet have the wealth of data supporting it that has been generated by the social-adaptive perspective using the TOSCA. Thus, before a dominant perspective can be identified, researchers need to (1) do more research assessing how the social-adaptive perspective compares to the functionalist perspective at the state level, and (2) do more trait research within the functionalist perspective to compare functionalist guilt- and shame-proneness measures with the TOSCA.

The UK economy is overly reliant on unsustainable production and consumption practices, depleting finite resources at rates that will increase production costs, business risk and economic instability. This over-consumption produces emissions and waste that cause climate change and environmental degradation, impacting on the wellbeing of people in the UK and beyond. The Resource Recovery from Waste programme (RRfW) promotes a transition towards waste and resource management in a circular economy that restores the environment, creates societal benefits and promotes clean growth by engaging relevant actors in the transition process. RRfW collaborates with academia, government, and industry to co-produce a shared vision and approach to realise such a transition. Reflecting insights from RRfW’s government engagement, this article presents a positive outlook for changing the UK economy and society. It envisions a long-term future for waste and resource management that maximises the value of materials by circulating them in the economy for as long as possible. Four themes and an approach are proposed, including recommendations for regulatory instruments and a stable policy framework. It recommends further collaborative research to capitalise on opportunities for economic growth, innovation and resilient infrastructure whilst contributing to quality jobs and welfare in all four UK nations.