The development of multiple drug resistant (MDR) cancer all too often signals the need for alternative toxic therapy or palliative care. Our recent in vivo and in vitro studies using canine MDR lymphoma cancer cells demonstrated that the Anaphase Promoting Complex (APC) is impaired in MDR cells compared to normal canine control and drug sensitive cancer cells. Here, we sought to establish whether this phenomena is a generalizable mechanism independent of species, malignancy type or chemotherapy regime. To test the association of blunted APC activity with MDR cancer behavior, we used matched parental and MDR MCF7 human breast cancer cells, and a patient derived xenograft (PDX) model of human breast cancer. We show that APC activating mechanisms, such as APC subunit 1 (APC1) phosphorylation and CDC27/CDC20 protein associations, are reduced in MCF7 MDR cells when compared to chemosensitive matched cell lines. Consistent with impaired APC function in MDR cells, APC substrate proteins failed to be effectively degraded. Similar to our previous observations in canine MDR lymphoma cells, chemical activation of the APC using Mad2 Inhibitor-1 (M2I-1) in MCF7 MDR cells enhanced APC substrate degradation and resensitized MDR cells in vitro to the cytotoxic effects of the alkylating chemotherapeutic agent, Doxorubicin (DOX). Using cell cycle arrest/release experiments we show that chemo-sensitive and -resistant MCF7 cells progress through the cell cycle at similar rates, but mitosis is delayed in MDR cells with elevated substrate levels. When treated with M2I-1, MDR cells progress through mitosis at a faster rate that coincides with reduced levels of APC substrates. In our PDX model, mice growing a clinically-MDR human breast cancer tumor show significantly reduced tumor growth when treated with M2I-1, with evidence of increased DNA damage and apoptosis. Thus, our results strongly support the hypothesis that APC impairment is a driver of aggressive tumor development and that targeting the APC for activation has the potential for meaningful clinical benefits in treating recurrent cases of MDR malignancy.

It has been proposed that the Monster of Troy, depicted in a 6th Century BC Corinthian vase, is the earliest artistic record of a vertebrate fossil, possibly a Miocene giraffe (Samotherium sp.). I analyzed the giraffe hypothesis under four approaches: a double-blind random design in which 78 biologists compared the vase skull with Samotherium and several reptiles; an informed survey of 30 students who critically assessed the hypothesis; a computerized image comparison; and a morphological comparison. All of them rejected the giraffe hypothesis. Eye and teeth types unambiguously discard a fossil or living mammal as the model, which more probably was an extant carnivorous reptile.

This paper explores the dynamics of political competition, resource availability, and conflict through a simulation-based approach. Utilizing agent-based models (ABMs) within an evolutionary game theoretical framework, we investigate how individual behaviors and motivations influence collective outcomes in civil conflicts. Our study builds on the theoretical model developed by Basuchoudhary et al. (2023), which integrates factors such as resource availability, state capacity, and political entrepreneurship to explain the evolution of civil conflict. By simulating boundedly rational agents, we demonstrate how changes in resource availability and state capacity can alter the nature of civil conflict, leading to different equilibrium outcomes. The findings highlight the importance of understanding individual motivations and adaptive behaviors in predicting the stability and resolution of conflicts. This research contributes to the growing body of literature on the use of agent-based models in evolutionary game theory and provides valuable insights into the complex interactions that drive civil violence.

Understanding ecological interactions is a key in managing phytopathology. Although entomologists rely mostly on both traditional molecular methods and morphological characteristics to identify pests, next-generation sequencing is becoming the go-to avenue for scientists studying fungal and oomycete phytopathogens. These organisms sometimes infect plants together with insects. There are many relationships yet to be discovered and much to learn about how these organisms interact with one another. Considering the growing number of exotic insect introductions in Canada, a high-throughput strategy for screening those insects is already implemented by the Canadian Food Inspection Agency (CFIA). However, no plan is deployed to investigate the phytopathogenic fungal and oomycete species interacting with insects. Metagenomics analysis was performed on the preservation fluids from CFIA’s insect traps across Canada. Using the Ion Torrent PGM technology and fusion primers for multiplexing and indexing, community profiling was conducted on the different semiochemicals used in the insect traps and the various areas where these traps were placed. Internal transcribed spacer 1 (fungi and oomycetes) and adenosine triphosphate synthase subunit 9-nicotinamide adenine dinucleotide dehydrogenase subunit 9 spacer amplicons were generated. Although direct links between organisms could not be established, moderately phytopathogenic fungi (e.g., Leptographium spp. and Meria laricis) and oomycetes (mainly Peronospora spp. and Pythium spp.) unique to every type of semiochemical were discovered. The entomopathogenic yeast Candida michaelii was also detected. This project demonstrated our ability to screen for unwanted species faster and at a higher scale and throughput than traditional pathogen diagnostic techniques. Additionally, minimal modifications to this approach would allow it to be used in other phytopathology fields.

In 2011 over 1.7 million people were hospitalized because of a fragility fracture, and direct costs associated with osteoporosis treatment exceeded 70 billion dollars in the United States. Failure to reach and maintain optimal peak bone mass during adulthood is a critical factor in determining fragility fracture risk later in life. Physical activity is a widely accessible, low cost, and highly modifiable contributor to bone health. Here, we will review the evidence linking exercise and physical activity to bone health in women. Bone structure and quality will be discussed, especially in the context of clinical diagnosis of osteoporosis. We will review the mechanisms governing bone metabolism in the context of physical activity and exercise. Questions such as, when during life is exercise most effective, and what specific types of exercises improve bone health, will be addressed. Finally, we will discuss some emerging areas of research on this topic, and will summarize areas of need and opportunity.

Koalas (Phascolarctos cinereus) are one of Australia's most charismatic native small marsupial species. Unfortunately, populations of koalas are rapidly declining throughout Australia and they continue to face increasing pressure from a changing ecosystem. Negative stimulants in the environment can elicit stress responses through activation of the hypothalamic-pituitary-adrenal (HPA) axis. Depending on the duration of the negative stimulant, the stress response can lead to either acute or chronic side effects, and is shown through the activation of the neuroendocrine stress system and the release of glucocorticoids (e.g., cortisol). Wild koalas entering clinical care face novel stressors that can be out of a wildlife carer's control. In this pilot study, we monitored physiological stress in three wild koalas at a wildlife rehabilitation centre in New South Wales, Australia. Acute and chronic stress was indexed non-invasively, with faecal samples taken to evaluate acute stress, and fur samples taken to evaluate chronic stress. Sampling occurred sporadically over four months, from the start of September 2018 to the end of December 2018. Results attempt to understand the stress response of koalas to negative stimulants in the environment by comparing faecal glucocorticoids on days where a known stressor was recorded with days where no known stressor was recorded. Furthermore, variations in faecal and fur glucocorticoids were compared between the three koalas in this study. To our knowledge, this is the first evidence of stress tracking of wild rescued koalas in a sanctuary. We suggest that further monitoring of baseline, acute and chronic stress will be needed to better understand how koalas respond to negative stimulants associated with clinical care.

COVID-19 was a terrible worldwide pandemic that caused a global public health crisis, with numerous deaths and a severe economic depression. To suppress the spread of COVID-19 and initiate patient isolation and contact tracing to reduce its effect, early diagnosis was required, with real-time reverse transcriptase polymerase chain reaction (RT-PCR) swab test being the most widely used. However, the RT-PCR test was sometimes found to be lengthy and inaccurate and; for that reason, in many cases of severe complications of COVID-19 pneumonia, chest screening with radiography imaging was preferred. In this paper, we carried out a study for COVID-19 detection from computed tomography images, and compared the obtained results using deep learning (DL) and support vector machine (SVM). The findings showed that, despite the excellent results shown by deep learning, the accuracy in predicting COVID-19 using SVM, in the presence of small databases, was slightly higher than DL. The execution time using SVM was also shorter

Mineral nutrition is essential for plant growth and interaction of plants with biotic and abiotic stresses. 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 (RE_D) was compared with the resorption efficiency of healthy (RE_S) leaves of KP mangoes. The concentrations of the total Ca, Mg, Cu, Fe, Mn, and Zn were lower in the HD trees than in the LD trees. But the total K content was higher in the HD trees, and its DOP index was sufficient, while the total K concentration was low and deficient level in LD trees. Moreover, DOP indices for total Ca, Mn, and Zn were less deficient in LD trees than in HD trees, and overall nutrient imbalances were exacerbated in HD trees. RE_D was significantly lower than RE_S for the total N, P, S, Cu, Fe, and Zn but significantly higher than RE_S 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.

Euler’s product formula over the primes and Euler’s zeta function equate to enshrine the Fundamental Theorem of Arithmetic that every integer > 1 is the product of a unique set of primes. The product formula has no zero, and with a domain ≤1 Euler’s zeta diverges. Dirichlet’s eta function η(s), negates alternate terms of zeta, permitting convergence when s∈C and Re(s) < 1, and its non-trivial zeros {ρ}, have a deep relationship with the distribution of the primes. The Riemann Hypothesis is that all the non-trivial zeros have Re(ρ) = 1/2. This work examines the symmetries in a partial Euler’s zeta series with a complex domain equating it to the difference between two finite vector series whose matched terms have mirror-image arguments, but whose magnitudes differ when Re(s) ≠ 1/2. Analytical continuation generates a modified eta series η_l(s), in which every l^th term is multiplied by (1-l). If the integer l is appropriately determined by the Im(s), similar paired finite vector series have a difference that closely follows η_l (s) and their terminal vectors intersect in a unique way permitting zeros only when Re(s) = 1/2. Furthermore, those vectors tracking the derivatives of the series, have a special relationship permitting zeros of the differential only when Re(s) > 1/2.

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.

The maintenance of skeletal muscle mass plays a fundamental role in health and issues associated with quality of life. Mechanical signals are one of the most potent regulators of muscle mass, with a decrease in mechanical loading leading to a decrease in muscle mass. This concept has been supported by a plethora of of human- and animal-based studies during the last 100 years and has resulted in the commonly used term of “disuse atrophy”. These same studies have also provided a great deal of insight into the structural adaptations that mediate disuse-induced atrophy. For instance, disuse results in radial atrophy of fascicles, and this is driven, at least in part, by radial atrophy of the muscle fibers. However, the ultrastructural adaptations that mediate these changes remain far from defined. Indeed, even the most basic questions, such as whether the radial atrophy of muscle fibers is driven by the radial atrophy of myofibrils and/or myofibril hypoplasia, have yet to be answered. In this review, we thoroughly summarize what is known about the macroscopic, microscopic, and ultrastructural adaptations that mediated disuse-induced atrophy and highlight some of the major gaps in knowledge that need to be filled.

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.

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.

To address the challenges of climate change and food security, the establishment of smart farm complexes is necessary. While there have been numerous studies on the productivity and environmental control of individual greenhouses, research on greenhouse complexes is considerably limited. Conducting environmental studies during the design phase of these complexes poses financial constraints and practical limitations in terms of on-site experiments. To identify potential issues that may arise when developing large-scale greenhouse complexes, it is possible to utilize modeling techniques using Computational Fluid Dynamics (CFD) to assess environmental concerns and location issues before constructing the facilities. Consequently, simulating large-scale CFD models that incorporate multiple greenhouses and atmospheric conditions simultaneously presents significant numerical challenges. The objective of this study was to develop a guideline for verifying CFD models for a large-scale Venlo greenhouse, where acquiring field data before construction is not feasible for designing a greenhouse complex. The verification processes of the CFD models were conducted using 2D and 3D iterative simulations of a 2-hectare greenhouse model, using the improved Grid Independence Test (GIT) and wall Y+ approaches. Subsequently, the aerodynamic characteristics were analyzed in a 3D greenhouse model to access its performance when the wind direction was 90° in summer season. The findings revealed that a grid resolution of 0.8 meters and a first layer height of 0.04 meters were suitable for developing large-scale greenhouse models, resulting in a low Root Mean Square Error (RMSE) of 3.9% and a high coefficient of determination (R2) of 0.968. This process led to a significant reduction of 38% in the number of grid cells. These results will serve as design standards for large-scale greenhouses.

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.

The paper is to examine the influence of business innovation, business expansion, product and service development, working capital, machinery and equipment on financing choices in the western part of Nigeria. To determine the effect on financing choices, a logistic regression analysis was used. The results in an impressive manner indicate that entrepreneur, essentially with working capital (WC), machinery and equipment (ME) requirement and business innovation (BI) used internal funding sources while business expansion (BE) and product and service development (PS) lean toward external funding sources and the more established and larger firm utilizes debt financing. The approach and the experiential findings offer an unprecedented degree of investigation from an academic point of view through the previous study on Nigeria entrepreneur. Similarly, the experimental results will strengthen the entrepreneur's knowledge, awareness and perception. Through the capabilities of the entrepreneurs, they can prepare and adapt in accordance with the business condition they conduct business and to help them in their choice procedure regarding the capital structure of their organization in the midst of an interval when the fuss of entrepreneur funding is gradually elicited in the Nigerian climate.

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.

It is well known that the primes and prime powers have a deep relationship with the nontrivial zeros of Riemann’s zeta function. This is a reciprocal relationship. The zeros and the primes are encoded in each other and are reciprocally recoverable. Riemann’s zeta is an extended or continued version of Euler’s zeta function which in turn equates with Euler’s product formula over the primes. This paper shows that the zeros of the converging Dirichlet or Catalan beta function, which requires no continuation to be valid in the critical strip, can be easily determined. The imaginary parts of these zeros have a deep and reciprocal relationship with the odd primes and odd prime powers. This relationship separates the odd primes into those having either 1 or 3 as a remainder after division by 4. The vector pathway of the beta function is such that the real part of its zeros has to be a half.

Background User fee exemption for maternal and child health care service policy was introduced with a focus on providing free caesarean sections (CS) in Nigeria from 2011 to 2015. This policy had a positive impact on access to facility-based delivery, but its effect on socioeconomic and geographical inequality remains unclear. This study’s main objective is to examine access to birth by CS in the context of free maternal health care. Specifically, the study examines socio-demographic and geographical inequality in access to birth by CS among women who gave birth between 2011 and 2015 under the free maternal health care policy using a population-based survey data obtained from two of the six main regions of the country. Methods Data were obtained from 1227 women who gave birth during the period the policy was in operation selected using cluster random sampling between May and August 2016. Adjusted and unadjusted binary logistic regression models were used to examine whether there is socio-demographic and geographical inequality in access to birth by caesarean section. Results The overall caesarean section rate of 6.1% was found but varies by income (14.1% in monthly income of over $150 versus 4.9% in income of $150 and below), education (11.8% in women with higher education versus 3.9% among women with secondary education and less) and place of residence (7.8% in urban areas versus 3.6% in rural areas). Women who earn a monthly income of $150 or less were 48% less likely to have a birth by CS compared to those who earn more. Compared to women who were educated to tertiary level, women who had secondary education or less were 54% less likely to have birth by caesarean section. Conclusion This study shows that inequality in access to CS persists despite the implementation of free maternal health care services. Given the poor access to facilities with capabilities to offer CS in most rural areas, free maternal healthcare policy is not enough to make birth by CS universally accessible to all pregnant women in Nigeria.

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.

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.

As with all new fields of discovery, work on the biological role of G-quadruplexes (GQ) has produced a number of results that at first glance are quite baffling, sometimes because they do not fit well together, but mostly because they are different from commonly held expectations. Like other classes of flipons, those that form G-quadruplexes have a repeat sequence motif that enables the fold. The canonical DNA motif (G3N1-7)3G3, where N is any nucleotide and G is guanine, a feature that is under active selection in avian and mammalian genomes. The involvement of G-flipons in genome maintenance traces back to the invertebrate Caenorhabditis elegans and to ancient DNA repair pathways. A role for GQ in transcription is supported by the observation that yeast Rap1 protein binds both B-DNA, in a sequence-specific manner, and GQ, in a structure-specific manner, through the same helix. Other sequence-specific transcription factors (TF) also engage both conformations to actuate cellular transactions. Noncoding RNAs can also modulate GQ formation in a sequence-specific manner and engage the same cellular machinery as localized by TF, linking the ancient RNA world with the modern protein world. The coevolution of noncoding RNAs and sequence-specific proteins is supported by studies of early embryonic development, where the transient formation of G-quadruplexes coordinates the epigenetic specification of cell fate.

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.

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.

The structure of synthetic mRNAs as used in vaccination against cancer and infectious diseases contain specifically designed caps followed by sequences of the 5’ untranslated repeats of β-globin gene. The strategy for successful design of synthetic mRNAs by chemically modifying their caps aims to increase resistance to the enzymatic deccapping complex, offer a higher affinity for binding to the eukaryotic translation initiation factor 4E (elF4E) protein and enforce increased translation of their encoded proteins. However, the cellular homeostasis is finely balanced and obeys to specific laws of thermodynamics conferring balance between complexity and growth rate in evolution. An overwhelming and forced translation even under alarming conditions of the cell during a concurrent viral infection, or when molecular pathways are trying to circumvent precursor events that lead to autoimmunity and cancer, may cause the recipient cells to ignore their differential sensitivities which are essential for keeping normal conditions. The elF4E which is a powerful RNA regulon and a potent oncogene governing cell cycle progression and proliferation at a post-transcriptional level, may then be a great contributor to disease development. The mechanistic target of rapamycin (mTOR) axis manly inhibits the elF4E to proceed with mRNA translation but disturbance in fine balances between mTOR and elF4E action may provide a premature step towards oncogenesis, ignite pre-causal mechanisms of immune deregulation and cause maturation (aging) defects.

Survival models have become popular for credit risk estimation. Most current credit risk survival models use an underlying linear model. This is beneficial in terms of interpretability but is restrictive for real-life applications since it cannot discover hidden nonlinearities and interactions within the data. This study uses discrete time survival models with embedded neural networks as estimators of time to default. This provides flexibility to express nonlinearities and interactions between variables, and hence allows for models with better overall model fit. Additionally, the neural networks are used to estimate Age-Period-Cohort (APC) models so that default risk can be decomposed into time components for loan age (maturity), origination (vintage) and environment (e.g., economic, operational and social effects). These can be built as general models, or as local APC models for specific customer segments. The local APC models reveal special conditions for different customer groups. The corresponding APC identification problem is solved by a combination of regularization and fitting the decomposed environment time risk component to macroeconomic data, since the environmental risk is expected to have a strong relationship with macroeconomic conditions. Our approach is shown to be effective when tested on a large publicly available US mortgage data set. This novel framework can be adapted by practitioners in the financial industry to improve modelling, estimation and assessment of credit risk.

Theories about consciousness—what it is/is not; who does/does not possess it; included/excluded functional modes; how/when it appears to be operational—are regularly published in books and articles. This essay opines that while many, if not most, of those speculations contain elements properly subsumed within a comprehensive doctrine, none satisfactorily fulfills its subject’s immense scope. Consciousness = Metaphysics + Physics + Biology is intended to rectify the situation by providing omitted components. As the title states, this is a wide-ranging approach neglecting many relevant details found in cited references, but also including ideas not found elsewhere in the easily accessible literature.

Analysis of tRNA sequence structural features from forty mammals proves neither isoacceptors nor isodecoders are degenerate, and model organisms are inadequate representatives for multiple aspects of the translational process. It is proposed tRNA participate in protein construction beyond mere transport of amino acids to ribosomes: specifically, to facilitate amino acid modification and promote development of protein folding characteristics.

Training supervised machine learning models requires labeled examples. A judicious choice of examples is helpful when there is a significant cost associated with assigning labels. This article improves upon a promising extant method – Batch-mode Expected Model Change Maximization (B-EMCM) method – for selecting examples to be labeled for regression problems. Specifically, it develops and evaluates alternate strategies for adaptively selecting batch size in B-EMCM. By determining the cumulative error that occurs from the estimation of the stochastic gradient descent, a stop criteria for each iteration of the batch can be specified to ensure that selected candidates are the most beneficial to model learning. This new methodology is compared to B-EMCM via mean absolute error and root mean square error over ten iterations benchmarked against machine learning data sets. Using multiple data sets and metrics across all methods, one variation of AB-EMCM, the max bound of the accumulated error (AB-EMCM Max), showed the best results for an adaptive batch approach. It achieved better root mean squared error (RMSE) and mean absolute error (MAE) than the other adaptive and non-adaptive batch methods while reaching the result in nearly the same number of iterations as the non-adaptive batch methods.

Corona viruses cause extensive SARS epidemics via super spread events (SSE). Due to variation in infection risk and heterogeneity of reproduction numbers specific distinction between SSE’s and typical case events is essential. SARS transmissions unveil a complex scenario in which SSE’s are shaped by multiple factors. Specific screening strategies for infection emergence within potential super spreading groups will help to efficiently control the SARS-2 pandemic and alleviate the partially effective general restriction measures.

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.

This paper considers the problem of quantifying the quality of a model selection problem for a graphical model. The model selection problem often uses a distance measure such as the Kulback-Leibler (KL) distance to quantify the quality of the approximation between the original distribution and the model distribution. We extend this work by formulating the problem as a detection problem between the original distribution and the model distribution. In particular, we focus on the covariance selection problem by Dempster, [1], and consider the cases where the distributions are Gaussian distributions. Previous work showed that if the approximation model is a tree, that the optimal tree that minimizes the KL divergence can be found by using the Chow-Liu algorithm [2]. While the algorithm minimizes the KL divergence it does not minimize other measures such as other divergences and the area under the curve (AUC). These measures all depend on the eigenvalues of the correlation approximation measure (CAM). We find expressions for KL divergence, log-likelihood ratio, and AUC as a function of the CAM. Easily computable upper and lower bounds are also found for the AUC. The paper concludes by computing these measures for real and synthetic simulation data.

A paper in this journal on decamethylcyclopentasiloxane (D5) used unreliable methods to reach unreliable conclusions. The authors concluded that D5 exposure should be viewed as causing human reproductive disorders and should be considered a developmental toxicant, that is, toxic to the developing embryo. The inadequate methods could not have answered the authors' research questions, and the paper should be withdrawn.

Proof of the Riemann hypothesis is obtained using the properties of the Gamma function, the Bernoulli function, and limitations imposed by the rational relations of the complex roots of the Riemann zeta function, and the rational relations of the complex Gamma functions.

This study examines whether government spending efficiency is associated with differential effects of public investment on debt-to-GDP ratio for a panel data consisting of 16 developing countries in Asia-Pacific region over the period 2007-2017. Public investment is central to implementing the UN 2030 Agenda for Sustainable Development — but high debt-to-GDP ratio poses a key risk. The empirical results indicate that public investment efficiency moderates debt-to-GDP ratio whereas public investment in the midst of public sector corruption accentuates debt-to-GDP ratio. The results have important policy implications.

Long COVID (Post-Acute Sequelae of COVID-19, PASC) is a consequence of infection by SARS-CoV-2 that continues to disrupt the well-being of millions of affected individuals for many months beyond their first infection. While the exact mechanisms underlying PASC remain to be defined, hypotheses regarding the pathogenesis of Long COVID are varied and include (but are not limited to) dysregulated local or systemic inflammatory responses, autoimmune mechanisms, viral-induced hormonal imbalances and long-term persistence of virus and/or fragments of viral RNA or proteins. This review article is based on a comprehensive review of the wide range of symptoms most often observed in long COVID and an attempt to integrate that information into a plausible hypothesis for the pathogenesis of PASC. In particular, it is proposed that longterm dysregulation of the gut in response to viral persistence could lead to the myriad of symptoms observed in PASC.

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.

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.

Research into health, particularly social and psychological health, is crucial. Ultimately, an in-depth understanding of social and psychological health will more than promote well-being. Technology research is indispensable, particularly concerning health and the built environment, given the need to create holistic and supportive frameworks for well-being. Moreover, because literature reviews establish the foundation for academic inquiries, they provide valuable overviews for foresight into grey research areas, particularly multi-disciplinary research like health technology and the built environment. Hence, this study aims to discover the existing themes on health, technology, and built-environment nexus subjects while revealing the grey areas and suggesting proactive areas for future research. The objectives drove this aim to: 1. investigate the implications of technology for the social and psychological dimensions of health; 2. uncover the likelihood of a nexus between health, technology, and the built environment; and 3. highlight new research perspectives for the concluding seven years of the SDGs (2024–2030). The review results highlighted ten themes around which a nexus exists between health, technology, and the built environment; they also pointed out new research perspectives for the next seven years (up to 2023).

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.

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.

Many accidents, such as those involving collisions or trips, appear to involve failures of vision; but the association between accident risk and vision as conventionally assessed, is weak or absent. We addressed this conundrum by embracing the distinction inspired by neuroscientific research, between vision for perception and vision for action. A dual-process perspective predicts that accident vulnerability will be associated more strongly with vision for action than vision for perception. Older and younger adults, with relatively high and relatively low self-reported accident vulnerability (Accident Proneness Questionnaire), completed three behavioural assessments targeting: vision for perception (Freiburg Visual Acuity Test); vision for action (Vision for Action Test - VAT); and the ability to perform physical actions involving balance, walking and standing (Short Physical Performance Battery). Accident vulnerability was not associated with visual acuity or with performance of physical actions; but was associated with VAT performance. VAT assesses the ability to link visual input with a specific action –launching a saccadic eye movement as rapidly as possible, in response to shapes presented in peripheral vision. The predictive relationship between VAT performance and accident vulnerability was independent of age, visual acuity and physical performance scores. Applied implications of these findings are considered.

The lab-on-a-chip concept, enabled by microfluidic technology, promises the integration of multi-ple discrete laboratory techniques into a miniaturised system. Research into microfluidics has generally focused on the development of individual elements of the total system (often with rela-tively limited functionality), without full consideration for integration into a complete fully opti-mised and miniaturised system. Typically, the operation of many of the reported lab-on-a-chip devices is dependent on the support of a laboratory framework. In this paper, a demonstrator platform for routine laboratory analysis is designed and built, which fully integrates a number of technologies into a single device with multiple domains such as fluidics, electronics, pneumatics, hydraulics, and photonics. This facilitates the delivery of breakthroughs in research, by incorpo-rating all physical requirements into a single device. To highlight this proposed approach, this demonstrator microsystem acts as a fully integrated biochemical assay reaction system. The re-sulting design determines enzyme kinetics in an automated process and combines reservoirs, three-dimensional fluidic channels, optical sensing, and electronics in a low-cost, low-power and portable package.

This study evaluated gas mixtures of carbon dioxide (CO2) associated with nitrogen (N2) as al-ternatives to the use of CO2 in two phases to improve the welfare of broiler chickens at slaugh-ter. Broilers were exposed to one of three treatments: 40C90C (1st phase: <40% CO2 for 2 min; 2nd phase: >90% CO2 and <2% O2 for 2 min, n=92), 40C60N (40% CO2, 60% N2 and <2% O2 for 4 min, n=79), or 20C80N (20% CO2, 80% N2 and <2% O2 for 4 min, n=72). The time to onset of loss of consciousness (LOC) and death was assessed by brain activity (EEG) and behaviour. Behaviour also allowed characterisation of the aversive response to the treatments. Exposure to 40C60N and 20C80N induced LOC faster (19 s [14 – 30 s] and 21 s [16 – 37 s], respectively) but also with less inter-individual variability compared to 40C90C (53 s [26 – 156 s], P < 0.001) and birds took less time to die (40C60N: 64 s [43 – 108 s]; 20C80N: 70 s [45 – 88 s]; 40C90C: 177 s [89 – 212 s], P < 0.001). The 40C90C birds not only experienced more aversion during induction to LOC but are at risk of remaining conscious when the CO2 concentration is increased in the 2nd phase. From an animal welfare point of view, 40C60N provided the highest welfare, followed by 20C80N and 40C90C.

This study sought to improve the nutritional, functional and biochemical properties of pearl millet through malting and fermentation. Moringa oleifera leaf powder (MLP) was used as a fortificant. Mixture design was used to find optimal proportions for each of the components that yield a high protein and or low saturated fat content. Twelve mixtures with varying ratios of fermented, and malted pearl millet flour ranging between 30–65%, and MLP between 5–15% were generated through I-Optimal mixture design. The mixtures were wet-cooked, freeze-dried and analyzed for protein and fat content. The data obtained were fitted to a linear mixture model and the search for the optimum was done using Numerical Optimization for maximising protein and minimising saturated fat. The linear model was suitable for explaining variation for total protein and saturated fat with r2 of 0.50 and 0.51, respectively. Increasing MLP increased protein content. Two final formulations were generated through the optimization process. Pearl millet’s protein content increased by up to 22% while saturated fat decreased by up to 13%. Ash content increased by 75%. Polyphenol content and oxygen radical absorbance capacity increased by 80% and 25%, respectively. Final and peak viscosity were reduced by 90% and 95%, respectively.

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.

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.

Superantigens are unconventional antigens which recognise immune receptors outside the usual binding sites e.g. complementary determining regions (CDRs), to elicit a response within the target cell. T-cell superantigens crosslink T-cell receptors and MHC Class II molecules on antigen-presenting cells, leading to lymphocyte recruitment, induction of cytokine storms and T-cell anergy or apoptosis among many other effects. B-cell superantigens, on the other hand, bind immunoglobulin receptors on B-cells affecting opsonisation, IgG-mediated phagocytosis, and drive B-cells into apoptosis. Here, through a review of the structural basis for recognition of immune receptors by superantigens, we show that their binding interfaces share specific physicochemical characteristics when compared with other protein-protein interaction complexes. Given that antibody-binding superantigens have been exploited extensively in industrial antibody purification, these observations could facilitate further protein engineering to optimize the use of superantigens in this and other areas of biotechnology.

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.

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.

This study explored the effectiveness of natural additives in prolonging the life of cut roses. A Completely Randomized Design (CRD) was used, with four different treatments: distilled water (control), a sucrose solution, moringa leaf extracts, and a combination of sucrose and moringa. The roses were observed over eight days to assess various factors such as leaf drop, stem rotting, bent necks, petal drop, flower condition, and petal color. The results showed that the combined treatment of sucrose and moringa led to the highest number of leaf drops, with 15 leaves dropping by day five. Distilled water resulted in 12 dropped leaves, moringa extract caused four leaves to drop, and sucrose had the least impact with only two leaves dropping. The combination treatment also caused the most significant stem rotting (32.75 mm) and the most bent necks (14 roses). In contrast, roses treated with sucrose or moringa separately had better outcomes, with the least bent necks and minimal leaf drops. For petal drop, the combined treatment again had the worst results, with eight petals dropping, followed by distilled water with six petals. The overall flower condition was poorest with the combined treatment, scoring 1 (completely open/damaged), while roses treated with sucrose or moringa separately had better scores, indicating they remained fresher. Petal color was also most affected by the combined treatment, which resulted in a light brown color, whereas the separate treatments maintained a darker red hue. Hence, while sucrose and moringa are beneficial when used individually, their combination negatively impacts the longevity and appearance of cut roses.

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.

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.

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.

In the mammalian isocortex CD44, a cell surface receptor for extracellular matrix molecules, is present in pial-based and fibrous astrocytes of white matter, but not the protoplasmic astrocytes. In the hominid isocortex, CD44+ astrocytes comprise the subpial “interlaminar” astrocytes, sending long processes into the cortex. The hippocampus also contains similar astrocytes. We have examined all levels of the human CNS and found CD44+ astrocytes in every region. Astrocytes in white matter and astrocytes that interact with large blood vessels, but not capillaries in gray matter, are CD44+, the latter extending long processes into the parenchyma. Motor neurons in the brainstem and spinal cord, such as oculomotor, facial, hypoglossal, and in the anterior horn of the spinal cord, are surrounded by CD44+ processes, contrasting with neurons in the cortex, basal ganglia and thalamus. We found CD44+ processes that intercalate between ependymal cells to reach the ventricle and that show a location-specific presence. We also found a CD44+ astrocyte in the molecular layer of the cerebellar cortex. Protoplasmic astrocytes, which do not normally contain CD44, acquire it in pathologies like hypoxia and seizures.

The observation that certain therapeutic strategies for targeting inflammation benefit patients with distinct immune-mediated inflammatory diseases (IMIDs) is exemplified by the success of TNF blockade in conditions including rheumatoid arthritis, ulcerative colitis and skin psoriasis, albeit only for subsets of individuals with each condition. This suggests intersecting "nodes" in inflammatory networks at a molecular and cellular level may drive and/or maintain IMIDs, being “shared” between traditionally distinct diagnoses without mapping neatly to a single clinical phenotype. In line with this proposition, integrative tumour tissue analyses in oncology have highlighted novel cell states acting across diverse cancers, with important implications for precision medicine. Drawing upon advances in the oncology field, this narrative review will first summarise learnings from the Human Cell Atlas in health as a platform for interrogating IMID tissues. It will then review cross-disease studies to date that inform this endeavour, before considering future directions in the field.

The severe and complex COVID-19 symptoms, often needing hospital care, occur suddenly, late in the virus replication stage of SARS-CoV-2 infection. Hospitalised patients have tissue damage due to micro-clots at multiple sites. Could long-covid, also clinically variable, be a milder form caused by “nano-clots”, too small to cause detectable tissue damage? The timing and suddenness of the onset of serious disease needs an explanation. A paper reported on the first 20 children needing urgent hospital care. No child had any symptoms prior to suddenly becoming seriously ill, only one had a positive PCR test but all had positive SARS-CoV-2 antibody test. That finding indicated to me that this onset occurred at the moment of sero-conversion. An emerging viral moiety, the virion-IgG-antibody complex, has concentrations rapidly increasing, then decreasing. It is known that influenza-IgG-antibody-complex consists of many virions bound together by the antibody. It seems a reasonable step to propose that SARS-2, being a large virus and having many spike proteins, can form larger clumps of virus-IgG-antibody complexes than with influenza, the former being sufficiently large to initiate micro-clots. Therefore, my hypotheses is that the SARS-CoV-2 virion-antibody complex initiates micro-clot formation. Either before or after sero-conversion, the complex will be at too low a concentration to initiate micro-clots. To be useful, a hypothesis should be testable, provide explanations and give predictions. My presentation will give examples. I like the way that several apparently separate pieces of a jig-saw puzzle have come together to form a single picture. [I suggest that the reader scrolls down to the addenda [10,11 & 12] before reading the ICAR Poster]

Technological advancements must keep pace with earth’s rising demand for energy, while minimizing the carbon footprint on earth. One such option is using space based solar (SBS) radio frequency (RF) microwave power beaming. This innovative and novel technology is currently being explored to address terrestrial photovoltaic (PV) intermittency and provide a method to transmit power to other spacecraft in various orbits. This modality of power generation and distribution presents a new way to power terrestrial off-grid applications and earth orbiting spacecraft. In 1968, Dr. Peter Glaser published "Power from the Sun: Its Future", which serves as the foundation of this paper to revitalize scientific interest and efforts in this topic. This paper will primarily focus on the reliance of SBS initiatives on reusable launch vehicles (RLV) to place SBS spacecraft in a designated orbit, as well as the technological, economic, and operational challenges associated with power beaming to earth and other spacecraft. This includes a discussion of the variables from the operational environment that contribute or accelerate spacecraft end of life.

Pulsed electric fields of specific frequencies emitted by a glass plasma antenna tube have been shown to slow the growth of Acute Lymphoblastic Leukemia cells by as much as 43% when exposed to a series of frequencies between 156kHz and 162kHz. This narrow band of frequencies is termed a “Destructive Cancer Resonant Frequency Formant” (DCRFF).

The history of life on Earth has been shaped by a series of major evolutionary innovations. While some of these innovations occur repeatedly, some of the most important innovations are evolutionary singularities, arising only once. This fact has often been interpreted to mean that singularities are particularly difficult, low-probability evolutionary events, implying the long-term course of life on Earth is highly contingent. Alternatively, singularities could arise from evolutionary priority effects, where first-movers suppress subsequent independent origins. Here, we disentangle these hypotheses by examining the origins of phototrophy. The ability to use light for energy evolved independently twice, preserving information about their origins that is lost when examining singularities. We show that the two forms of phototrophy occupy opposite ends of key trade-offs: most importantly efficiency of light capture vs. return on investment. Our results suggest that the dual singularity of phototrophy exists due to evolutionary interactions between nascent phototrophs, within a phototrophic niche space too large for a single first mover to fill all niches and fully suppress all future innovation. While often ignored over geological time scales, ecological interactions and evolutionary priority effects may play a fundamental role in the tempo and mode of major evolutionary innovations.

Sedation is a ubiquitous practice in ICUs and NCCUs. It has the benefit of reducing cerebral energy demands, but also precludes an accurate neurologic assessment. Because of this, sedation is intermittently stopped for the purposes of a neurologic assessment, which is termed a neurologic wake-up test (NWT). NWTs are considered to be the gold-standard in continued assessment of brain-injured patients under sedation. NWTs also produce an acute stress response that is accompanied by elevations in blood pressure, respiratory rate, heart rate, and ICP. Utilization of cerebral microdialysis and brain tissue oxygen monitoring indicates that this is not mirrored by alterations in overall cerebral metabolism, and seldom affects oxygenation. The hard contraindications for the NWT are preexisting intracranial hypertension, barbiturate treatment, status epilepticus, and hyperthermia. However, hemodynamic instability, sedative use for primary ICP control, and sedative use for severe agitation or respiratory distress are considered significant safety concerns. Despite ubiquitous recommendation, it is not clear if additional clinically relevant information is gleaned through its use, especially with the contemporaneous utilization of multimodality monitoring. Various monitoring modalities provide unique and pertinent information about neurologic function, however, their role in improving patient outcomes and guiding treatment plans has not been fully elucidated. There is a paucity of information pertaining to the optimal frequency of NWTs, and if it differs based on type of injury. Only one concrete recommendation was found in the literature, exemplifying the uncertainty surrounding its utility. The most common sedative used and recommended is propofol because of its rapid onset, short duration, and reduction of cerebral energy requirements. Dexmedetomidine may be employed to facilitate serial NWTs, and should always be used in the non-intubated patient or if propofol infusion syndrome (PRIS) develops. Midazolam is not recommended due to tissue accumulation and residual sedation confounding a reliable NWT. Thus, NWTs are well tolerated in most patients and remain recommended as the gold-standard for continued neuromonitoring. Predicated upon one expert panel, they should be performed at least one time per day. Propofol or dexmedetomidine are the main sedative choices, both enabling a rapid awakening and consistent NWT.

Based on a rich data set of recoveries donated by a debt collection business, recovery rates for non-performing loans taken from a single European country are modelled using linear regression, linear regression with Lasso, beta regression and inflated beta regression. We also propose a two-stage model: beta mixture model combined with a logistic regression model. The proposed model allows us to model the multimodal distribution we find for these recovery rates. All models are built using loan characteristics, default data and collections data prior to purchase by the debt collection business. The intended use of the models is to estimate future recovery rates for improved risk assessment, capital requirement calculations and bad debt management. They are compared using a range of quantitative performance measures under K-fold cross validation. Among all the models, we find that the proposed two-stage beta mixture model performs best.

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.

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

A simple approach to enable water-management agencies employing free data to achieve the goal of using a single set of predictive equations for water-quality retrievals with satisfactory accuracy is proposed. Multiple regression-derived equations based on surface reflectance, band ratios, and environmental factors as predictor variables for concentrations of Total Suspended Solids (TSS), Total Nitrogen (TN), and Total Phosphorus (TP) were derived using a hybrid forward-selection method that considers Variance Inflation Factor (VIF) in the forward-selection process. Landsat TM, ETM+, and OLI/TIRS images were jointly utilized with environmental factors, such as wind speed and water surface temperature, to derive the single set of equations. The coefficients of determination of the best-fitting resultant equations varied from 0.62 to 0.79. Among all chosen predictor variables, ratio of reflectance of visible red (Band 3 for Landsat TM and ETM+, or Band 4 for Landsat OLI/TIRS) to visible blue (Band 1 for Landsat TM and ETM+, or Band 2 for Landsat OLI/TIRS) has a strong influence on the predictive power for TSS retrieval. Environmental factors including wind speed, remote sensing-derived water surface temperature, solar altitude, and time difference (in days) between the image acquisition and water sampling were found important in water-quality parameter estimation.

The paper describes problems with the current additive manufacturing chain before considering additive manufacturing as part of a modern manufacturing chain. Additive manufacturing can be used for near net-shape for finishing, for repair or for adding special features which cannot be made with traditional manufacturing. This paper describes how STEP-NC deals with these different scenarios in terms of accuracy, multi-material and variation of slice direction. The possibilities of multi-material objects also raises questions about the design of such objects and how these need to be handled by an advanced controller. The paper also describes non-planar slicing. Curved direction and cylindrical direction are shown to improve the accuracy of curved structure additive manufacturing. STEP-NC using boundary representation has better capability of depicting complex internal structures for additive processes. By using exact model of the final product represented by STEP-NC, the paper demonstrates improvements in data size reduction, slicing accuracy, and precise manipulation of internal structure.

The study used ERA5 reanalysis SST dataset re-gridded to a common grid of 0.25° X 0.25° spatial resolution (latitude × longitude) for the historic (1940–2014) and projected (2015–2100). The SST simulation under the SSP5-8.5 scenarios was carried out with output from 8 General Circulation Models (GCMs). The bias-corrected dataset was developed using Empirical Quantile Mapping EQM for the historical (1940-2015) and the future (2030-2100) while the CMIP6 model simulation was evaluated against the ERA5 monthly rainfall observed data for monthly and annual sea surface temperatures (SST) over the Gulf of Guinea. ). The CMIP6 models simulation for SST projection from 2030-20100 based on SSPS 8.5 SST is projected to increase by 4.61o (31oC) in 2030 to 35oC in 20100 in the coastal GOG and 2.6oC in the Western GOG (Sahel). The correlation coefficient (r) was used to evaluate the performance of the CMIP6 models and the analysis showed ACCESS 0.1,CAMS CSM 0.2, CAN ESM 0.3, CMCC, 0.3 and MCM, 0.4 indicating that all models performed well in capturing the climatological pattern of the SST. The.CMIP6 bias corrected model simulations showed increased SST warming over the GOG will be higher in the Far period end than the Near-term climate. The study affirmed that the CMIP6 projections can be used for multiple assessments related to climate and hydrological impact studies and for the development of mitigation measures under a warming climate

Therapeutic intervention for schizophrenia relies on blockade of dopamine D2 receptors in the associative striatum; however, there is little evidence for baseline overdrive of the dopamine system. Instead, the dopamine system is in a hyper-responsive state due to excessive drive by the hippocampus. This causes more dopamine neurons to be in a spontaneously active, hyper-responsive state. Antipsychotic drugs alleviate this by causing depolarization block, or excessive depolarization-induced dopamine neuron inactivation. Indeed, both first- and second-generation antipsychotic drugs cause depolarization block in the ventral tegmentum to relieve positive symptoms, whereas first-generation drugs also cause depolarization in the nigrostriatal dopamine system to lead to extrapyramidal side effects. However, by blocking dopamine receptors, these drugs are acting multiple synapses downstream from the proposed site of pathology: the loss of inhibitory influence over the hippocampus. An overactive hippocampus can not only drive the dopamine-dependent positive symptoms, but via its projections to the amygdala and the neocortex could also drive negative and cognitive symptoms, respectively. On this basis, a novel class of drugs that can reverse schizophrenia at the site of pathology, i.e. the hippocampal overdrive, could be effective in alleviating all three classes of symptoms of schizophrenia while also being better tolerated.

Enteropathogens, namely Salmonella and Campylobacter, are a concern in global public health and have been attributed in numerous risk assessments to a poultry source. During the last decade a large body of research addressing this problem has been published. The literature reviewed contains review articles on certain aspects of poultry production chain, however in the past decade there hasn’t been a review on the through production chain, farm to fork, production of poultry. This review, a pool of 514 articles were selected for relevance via a systematic screening process (from >7500 original search articles). These studies identified a diversity of management and intervention strategies for the elimination or reduction of enteropathogens in poultry production. Many studies were laboratory or limited field trials with implementation in true commercial operations being problematic. Entities considering using commercial anti-enteropathogen products and interventions are advised to perform an internal validation and fit for purpose trial as Salmonella and Campylobacter serovars and biovars may have regional diversity. Future research should focus on non-chemical application within the processing plant and how synergistic through chain intervention may contribute to reducing the overall carcass burden of enteropathogen, coupled with increased consumer education on safe handling and cooking of poultry.

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.

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.

During HIV-1 virus assembly the genomic RNA (vRNA) is selected for packaging by the viral protein Gag because it contains a specific packaging signal, Psi. While there have been numerous studies of Gag-Psi interactions, there is almost no information on kinetic aspects of this interaction. We have investigated the kinetics of Gag binding to different RNAs using switchSENSE DRX2 technology. We measured the association rate of Gag binding to monomeric Psi, to a “Multiple Binding Site Mutant” Psi that is inactive for genome packaging in vivo, and to a scrambled Psi. We discovered that Gag binds more rapidly to Psi RNA than to the mutant or scrambled RNAs. Furthermore, rapid Gag association kinetics are retained within sub-regions of Psi: Gag associates more rapidly with RNA containing only the 3’ two of the three Psi stem-loops than with monomeric RNA containing the 5’ two stem-loops or a scrambled RNA. No differences were detectable with individual Psi stem-loops. Interestingly, the rate of binding of Gag molecules to Psi increases with increasing Gag concentration, suggesting cooperativity in binding. The results are consistent with the hypothesis that selectivity in packaging derives from kinetic differences in initiation of particle assembly.

In the context of cognitive radio, smart city and Internet-of-Things, the need of advanced radio spectrum monitoring becomes crucial. However, surveillance of a wide frequency band without using extremely expensive high sampling rates devices is a challenging task. The recent development of compressed sampling approaches offers a promising solution to these problems. In this context, the Modulated Wideband Converter (MWC), a blind sub-Nyquist sampling system, is probably the most realistic approach and was successfully validated in real-world conditions. The MWC can be realized with existing analog components and there exist calibration methods which are able to integrate the imperfections of the mixers, filters and ADCs, hence allowing its use in real-world. The MWC underlying model is based on signal processing concepts such as filtering, modulation, Fourier series decomposition, oversampling and undersampling, spectrum aliasing, and so on, as well as in-flow data processing. In this paper we develop an MWC model which is entirely based on linear algebra, matrix theory and block processing. We show that this approach has many interests: straightforward translation of mathematical equations into simple and efficient software programming, suppression of some constraints of the initial model, and providing a basis for the development of an extremely fast system calibration method. With a typical MWC acquisition device we obtained a speed up of a factor greater than 20 of the calibration computation time, compared with a previous implementation.

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.

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.

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.

The current study explores the impact of celebrity endorsements and social media platforms on promoting sustainable consumer behavior in Nigerian tourism industry. The study employs Mentionlytics software to analyze online documents and examine how political celebrities and social media platforms (Twitter and Facebook) influence consumer behavior and decision-making processes within the tourism industry. The findings in phase 1 suggest that celebrity endorsements and social media platforms have a positive impact on sustainable consumer behavior. The results in phase 2 suggest that political celebrities engage followers on Facebook based on the 70% share. However, no engagement was found on Twitter based on the zero percent (0%) share, suggesting that Facebook enables political celebrities to promote sustainable tourism. The study contributes to the literature on sustainability and celebrity endorsements, offering insights for destination marketers and policymakers in the Nigerian tourism industry.

Background This study aimed to identify the prominent risk factors that may trigger danger signals of early onset of vascular deregulation in T1D. The risk factors we have identified may serve as dual-purpose biomarkers of rapid diagnosis that offer prospective tailor-made resolution therapeutics. Methods The healthy control (HC) was compared with individuals diagnosed with T1D for the risk factors of vascular deregulation in published research studies from year 2013 to 2023. The PubMed, Web of Science and Google Scholar databases were searched from 1/1/2013 to 1/9/2023. The risk of bias was assessed with the Cochrane (ROBINS-I ) tool, which is relevant to clinical subjects. A random effect model for continuous data was followed and analysed by RevMan 5.4 and GraphPad Prism software. Results 80 relevant case-control studies having 5293 HC and 7492 T1D patients were included. The age and sex-matched HC consisted of persons free of disease and not under any medication while clinical subjects of all age groups were included. 28 risk factors were grouped into six primary outcome models, all of which favoured the T1D synonymous with a high risk of CVD. Conclusions Our findings have strong implications for improving the quality of life and health economics related to vascular disease in T1D. HbA1c% is the most effective biomarker, followed by FBG, LDL-C, and AI% which the clinicians could evaluate using a simple blood test or non-invasive techniques. (Protocol registered at https://www.crd.york.ac.uk/prospero/ CRD42022384636).

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

Traditional education, particularly at a university level isn’t necessarily very engaging1 or strong at building teamwork skills. Educational escape rooms are a recent game based learning2 approach which combines team based problem solving with a story-line and cryptic clues. In this3 paper we apply the concept of educational escape rooms to the telecommunications engineering4 classroombycreatingaseriesoftwoseparatescenarios,eachcontainingthreepuzzles. Ourevaluation5 is based on beta tester survey results which suggest that this will be an engaging and challenging6 tool for teaching telecommunications engineering. Although educational escape rooms are rapidly7 being deployed in education, these are the first educational escape rooms that specifically addresses8 the field of telecommunications engineering.

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

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.

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.

Achieving neuroprotection in ischemic stroke patients has been a multi-decade medical challenge. Numerous clinical trials were discontinued in futility and many were terminated in response to deleterious treatment effects. Recently however, several positive reports have generated the much-needed excitement surrounding stroke therapy. In this review, we describe the clinical studies that significantly expanded the time window of eligibility for patients to receive mechanical endovascular thrombectomy. We summarize the results available thus far for nerinetide, which can be considered the most promising neuroprotective agent yet for stroke treatment. Lastly, we reflect upon aspects of these successful trials in our own studies targeting the Kv2.1-mediated cell death pathway in neurons for neuroprotection. We propose that recent changes in the clinical landscape must be adapted by preclinical research in order to continue progressing toward the development of efficacious neuroprotective therapies for ischemic stroke.

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.

Background: Ongoing Primary and Secondary Education Development Program (PEDP & SEDP) has led to increase in enrollment of children in schools. This created a high demand for facilities such as classroom, chairs, laboratories, latrines and water supply. Water and latrines did not receive equal attention like others. National strategic plan for School Water Sanitation and Hygiene (SWASH) 2012-2017 was to address such challenges with objectives to improve SWASH by 2017. Hence this study aimed to evaluate the implementation of SWASH program in Ukerewe. Methodology: A cross sectional survey was done among 42 schools in the district with 40 schools being government owned. Systematic random sampling was used and data were collected using a structured interview which was pre-tested and amended prior to conducting fieldwork. UNICEF, WASH in Schools Monitoring Package observational check-list was used to assess sanitation facilities. Results: Findings from this study showed the latrine-hole to student ratio was 1:71 with only 31.3% of the latrines being in good clean condition and about half (59.5%) of the schools have no facilities for washing hands. For the schools with hand washing facilities only 21.4% have an effective hand washing practice (presence of soap and water). The most common source of water used was lake water (35.7%) with (42.9%) having water storage facilities. Conclusion: The study shows that most of the objectives of national strategic plan are yet to be implemented at Ukerewe. There is a need for minor repairs to complete new construction of SWASH facilities in Ukerewe.

The PI3K/mTOR signalling pathway plays a central role in the governing of cell growth, survival and metabolism. As such, it must integrate and decode information from both external and internal sources to guide efficient decision-making by the cell. To facilitate this, the pathway have evolved an intricate web of complex regulatory mechanisms and elaborate crosstalk with neighbouring signalling pathways, making it a highly non-linear system. Here, we describe the mechanistic biological details that underpin these regulatory mechanisms, covering a multitude of negative and positive feedback loops, feed-forward loops, competing protein interactions, and crosstalk with major signalling pathways. Further, we highlight the non-linear and dynamic network behaviours that arise from these regulations, uncovered through both computational and experimental studies. Given the pivotal role of the PI3K/mTOR network in cellular homeostasis and its frequent dysregulation in pathologies including cancer and diabetes, a coherent and systems-level understanding of the complex regulation and consequential dynamic signalling behaviours within this network is imperative for advancing biology and development of new therapeutic approaches.

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.

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.

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.

Lutein, a plant-derived xanthophyl-carotenoid, is an exceptional antioxidant and anti-inflammatory constituent found in food. Elevated concentrations of lutein found in human blood and plasma, due to high dietary intake, are beneficial against eye disease and improve cardiometabolic health. Lutein plays an important protective role against the development of neurological disorders, including Alzheimer’s disease (AD), multiple sclerosis (MS) and Parkinson’s disease (PD). It has also been shown to be beneficial for liver, kidney and respiratory health. Lutein, acting as a very strong antioxidant, can alleviate oxidative stress and downgrade reactive oxygen species (ROS). Oxidative stress is one of the key pathogenic mechanisms in post-COVID and mRNA vaccine injury syndromes. Recent in silico studies suggest that lutein and other naturally derived antioxidants, by docking at the site where the SARS-CoV-2 spike protein (SP) binds to the angiotensin enzyme type 2 (ACE2) receptor, may neutralize the SP-ACE2 interactions. Lutein can be added to a detoxification regimen to aid in clearing Spike protein and relieving symptoms. In agreement with Hippocrates’ dictum to “Let food be thy medicine,” this review establishes dietary lutein as a valuable therapy in the treatment of post-COVID syndrome, mRNA vaccine injury syndromes, and a wide range of other chronic illnesses.

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.