This paper introduces an innovative energy circuit that challenges conventional understandings of energy conservation, marking a significant departure from traditional frameworks. Seeking to enhance energy generation within existing paradigms, this innovation holds promise for addressing pressing global issues such as the energy crisis and environmental sustainability, while also stimulating scientific inquiry. In contrast to prevalent misconceptions rooted in philosophical and scientific constraints, this study refutes the notion of generating energy from nothing and questions the viability of perpetual motion machines as conceptual models. Instead, it proposes a novel circuit design derived from an unconventional electrical short circuit, which is shown to disrupt the established principles of energy conservation. This circuit offers a transformative approach with diverse applications, including self-recharging capabilities for electric vehicles, bolstering microgrid infrastructure, and facilitating the integration of renewable energy sources. Transcending conventional scientific boundaries, this paper prompts philosophical reflections on the evolving nature of scientific exploration. Ultimately, the energy circuit represents a pivotal step towards mitigating the global energy crisis by reducing reliance on finite resources and fostering sustainability. The paper concludes by illustrating the circuit's potential to revolutionize energy systems and contribute to a more resilient and sustainable future.

Background: People with Williams syndrome (WS) are characterized with hypersociability, fluency in languages, and advantageous face-processing skills, leading to the proposal of a social module. Previous studies on the mentalizing abilities of people with WS using two-dimensional pictures and mindreading from eyes, including normal-like, delayed, and deviant behaviors, have yielded mixed results. This study thus examined the mentalizing ability of people with WS through structured computerized animations of false belief tasks to investigate whether inferences about other people’s minds can be improved in this population. Method: Participants were shown animations with unexpected location and content changes. After viewing each animation, participants had to answer four types of questions: character identification, reality, memory, and false belief. Their responses were recorded and analyzed. Results: Comprehension of false belief was observed in 4-year-old healthy children, whereas children with WS showed unsuccessful comprehension of false belief (until they attained a mental age of 5.3 years), suggesting an improvement in theory of mind resulting from viewing structured computerized animations. This age is earlier than that reported by previous studies for using theory of mind to pass false belief tests (8.5 years old), even challenging the age at which individuals failed to pass the tests (12.10 years old). Conclusions: Structured computerized animations enhanced the mentalizing ability of people with WS to a certain extent. Compared to the typically developing controls, people with WS presented with a lower developmental level in processing false belief tasks. The educational implication of this study is to develop computerized social skills interventions for people with WS.

Malawi has developed an excellent, nation-wide system for monitoring people infected with HIV and keeping track of key epidemic markers. Their success lies in two things: the focus on simplicity and the use of data collection not only to track the epidemic and identify problems but also to give regular feedback and support to every clinic in the country. This achievement is the more remarkable given that Malawi is one of the poorest countries in the world, ranking 190 out of 194 countries by GDP, but has one of the most severe epidemics of HIV in the world, ranking 9th out of 168 countries by HIV prevalence. We first discuss the current state and likely future epidemic trends in Malawi: unless we know where we are and where we are going we cannot decide what to do or how to do it to in order to achieve a better outcome. We then discuss the history and development of Malawi’s patient monitoring system, as reported in their Integrated HIV Program Reports,ix which have been published quarterly since the beginning of 2004. We consider the current state of patient monitoring and support as reflected in the most recent report for the third quarter (Q3) of 2016 and comment on some of the questions that this raises. Finally, we consider ways in which the current system could be improved by strengthening Malawi’s analytical capacity and making better use of this unique data set. The focus here is on HIV in adultsv because if ART is initiated early in all adults living with HIV this should include testing all pregnant women for HIV and starting them on treatment immediately. However, PMTCT is especially important and care must be given to reducing MTCT and identifying the long-term child survivors of mother-to-child transmission and this demands a complementary assessment. There is an ongoing debate about the relative merits of treatment and prevention in reducing transmission and it should be made clear that the primary reason for starting people on treatment early is that it is in the best interest of the individual patient to start treatment as soon as possible after becoming infected. Allowing a person’s immune system to deteriorate to any degree is not consistent with the clinician’s commitment to ‘first do no harm’ and even those with the highest CD4⁺ cell count are at a substantially increased risk of death. What matters, therefore, is to get as many people as possible onto ART, ensure that they remain virally suppressed, and consider prevention in this context.

This article explores the significant parallels between big tobacco companies and major social networking sites regarding their influence on public health and society. While acknowledging the fundamental differences in their products and services, the paper scrutinises both industries through five primary lenses: addiction, misinformation, lack of regulation, harm to public health, and youth targeting. Both industries exhibit addictive characteristics, have faced criticism for the spread of misinformation, operate with limited regulation and transparency, and have raised concerns about targeting young demographics. Moreover, the potential harm to public health is a significant concern, with tobacco leading to well-established physical health issues. At the same time, excessive social media use has been linked to psychological harm, particularly among young users. The comparison underscores the necessity for greater regulation and oversight of social media companies, highlighting the urgent need for more comprehensive policies to mitigate potential harm and safeguard public health in the digital age.

South Africa is afflicted with the worst epidemic of HIV in the world a legacy of the system of oscillating migrant labour in the region and the consequent social disruption that was the legacy of Apartheid. The initial response from the national government was slow and ineffective but once the magnitude of the epidemic became apparent the government began to respond. The investment in HIV- and TB-related activities in 2013 was R22 Bn or (US$2.5; 2013 exchange rate) of which the South Africa government contributed 80% and the Presidents Emergency Plan for AIDS Relief (PEPFAR) 17%. South Africa now has the more people on anti-retroviral therapy than any other country and treatment is being started much sooner after infection. Much of the best biomedical, virological, immunological, mathematical and social science around the treatment and prevention of HIV and AIDS and the associated epidemic of TB has been done by South African’s and their international collaborators. If the efforts to control the epidemic are maintained South Africa is on track to meet the UNAIDS 90-90-90target by 2020 and to End AIDS by 2030 in spite of the magnitude of the problem. While individual, patient level data are increasingly available, especially in the Western Cape, much greater efforts need to be made to ensure that the information collected in this way is used to give feedback and support to clinic staff, to ensure that health clinics are providing the best possible service, and to individual patients and people living with HIV to ensure that they are receiving the best possible care and support. South Africa needs to make better use of the rich and detailed data that are being collected from individual clinics and their patients to identify problems or difficulties at the clinic level and to ensure that individual patients are retained on treatment, are virally suppressed and receive the best possible care and support.

The COVID-19 virus was first detected in Wuhan, China and its genesis was traced to infected bats, passed through an intermediate host to humans. COVID-19 or “Coronavirus” reached approximately 4 million confirmed cases in the United States by July 2020. The spread of this virus has affected both social and economic affairs on a global scale with more than 15 million confirmed cases worldwide in July 2020. The pandemic has proven a global public health and socio-economic crisis. In addition, the shelter-in-place orders provide an unprecedented opportunity for examining the resulting reduction in greenhouse gases and aerosols on the atmosphere. The Sentinel-5P satellite has shown distinct changes in atmospheric compounds over the COVID-19 epicenter in Wuhan. After Texas, U.S.A. established similar shelter-in-place orders to prevent the spread of the virus, the state’s industrial activity experienced an economic slowdown. This paper quantifies the changes in the atmosphere during the time of the COVID-19 slowdown over major cities in Texas and compares it to similar changes in Wuhan, China using satellite imagery.

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

Soybean seed sugars are among the most abundant beneficial compounds for human and animal consumption in soybean seeds. Higher seed sugars such as sucrose are desirable as it contributes to taste and flavor in soy-based food. Therefore, the objectives of this study were to use ‘Forrest’ by ‘Williams 82’ (F×W82) recombinant inbred line (RIL) soybean population (n=309) to identify quantitative trait loci (QTL) and candidate genes that control seed sugar (sucrose, stachyose, and raffinose) contents in two environments (North Carolina and Illinois) over two years (2018 and 2020). A total of 26 QTL that control seed sugars contents were identified and mapped on 16 soybean chromosomes (chrs.). Interestingly, five QTL regions were identified in both locations, Illinois and North Carolina, in this study on chrs. 2, 5, 13, 17, and 20. Amongst 57 candidate genes identified in this study, 16 were located within 10 Megabase (MB) of the identified QTL. Amongst them a cluster of four genes involved in the sugars’ pathway was collocated within 6 MB with two QTL that were detected in this study on chr. 17. Further functional validation of the identified genes could be beneficial in breeding programs to produce soybean lines with high beneficial sucrose and low raffinose family oligosaccharides.

The rapid expansion of social media and instant messaging applications, such as WhatsApp, has transformed how individuals and organizations communicate and engage. This think piece explores the potential of integrating WhatsApp as a customer relationship management (w-CRM) tool within the education sector to foster and sustain long-term relationships among students, teaching staff, and non-teaching staff. By leveraging real-time features and the widespread use of WhatsApp, educational institutions can create a more interactive and dynamic learning environment, benefiting all stakeholders involved. The literature highlights the importance of establishing clear frameworks for mutual engagement and interaction and the potential of w-CRM to improve communication between students' families and educational institutions. There are potential risks associated with the pervasive use of WhatsApp, and call for future research to explore strategies for mitigating these risks while maximizing the benefits of w-CRM in the education sector. Longitudinal studies are recommended to evaluate the long-term impact of w-CRM on stakeholder relationships, student outcomes, and overall institutional performance.

Antennas are crucial elements for wireless technologies, communications and power transfer across the entire spectrum of electromagnetic waves, including radio, microwaves, THz and optics. In this paper, we review our recent achievements in two promising areas: coherently enhanced wireless power transfer (WPT) and superdirective dielectric antennas. We show that the concept of coherently enhanced WPT allows improvement of the antenna receiving efficiency by coherent excitation of the outcoupling waveguide with a backward propagating guided mode with a specific amplitude and phase. Antennas with the superdirectivity effect can increase the WPT systems performance in another way, through tailoring of radiation diagram via engineering antenna multipoles excitation and interference of their radiation. We demonstrate a way to achieving the superdirectivity effect via higher-order multipoles excitation in a subwavelength high-index spherical dielectric resonator supporting electric and magnetic Mie multipoles. Thus, both types of antenna discussed here possess a coherent nature and can be used in modern intelligent antenna systems.

The emergence of Artificial Intelligence (AI) driven Keyword Spotting (KWS) technologies has revolutionized human to machine interaction. Yet, the challenge of end-to-end energy efficiency, memory footprint and system complexity of current Neural Network (NN) powered AI-KWS pipelines has remained ever present. This paper evaluates KWS utilizing a learning automata powered machine learning algorithm called the Tsetlin Machine (TM). Through significant reduction in parameter requirements and choosing logic over arithmetic based processing, the TM offers new opportunities for low-power KWS while maintaining high learning efficacy. In this paper we explore a TM based keyword spotting (KWS) pipeline to demonstrate low complexity with faster rate of convergence compared to NNs. Further, we investigate the scalability with increasing keywords and explore the potential for enabling low-power on-chip KWS.

Collatz conjecture (3x+1 problem) is a natural phenomenon in set theory that may be reconstructed using known combinatorics and order theory. Construction begins by selecting a specific order isomorphism with a bijectional order-embedding. Mapping by 3x+1 induces a unique property to only members of the mapped embedding. Under selective congruence from recursive division by two, that complex controls sequence behavior. This demonstration uses an order isomorphism consisting of two linear orders: the (1) odd positive integers and the always odd (2) Rule 50 Jacobsthal numbers, as the embedding. The argument proceeds by cardinality. When the order isomorphism is mapped under 3x+1, all Rule 50 Jacobsthal numbers are mapped to all the powers of four. This one-to-one correspondence guarantees that every odd integer is assigned to a Rule 50 Jacobsthal number, and subsequently, to a power of four. To align this construction with the conjecture, expand the set to all positive integers by showing that: (1) the powers of four embed the powers of two, in a natural way, and (2) the unique factorization of any positive even integer, not congruent to a power of two, is simply an odd integer, once the factorized power of two is divided out. In other words, if the initial choice for a positive integer is not congruent to a power of two, then recursion continues until a Rule 50 Jacobsthal number (guaranteed by cardinality) is attained. Since this value mapped by 3x+1 is always a power of four, repeated division by two will always send the sequence to one. Because this same process occurs for any choice of positive integer, Collatz conjecture is true.

U.S. Navy Surface Ship depot-level maintenance periods of performance were studied to develop a method for predicting maintenance durations. The need for the method has been highlighted by Navy leadership in recent media posts describing unacceptable maintenance delays and this research provides practitioners and decisionmakers with a reliable estimating tool. This study helps by putting forth a method that defines the rate of work accomplishment based on relevant variables. Using ordinary least squares models, this research revealed that the size of the contract obligation and the amount of shipyard work occurring simultaneously in the market are key variables in determining depot maintenance durations. With the knowledge found here, the next logical step is an optimization model for each U.S. Navy surface ship homeport.

This paper investigates the constructability of angles multiples of 3 within the framework of Euclidean geometry. It makes a significant contribution by presenting the first geometric construction for all such angles, offering a rigorous solution to a longstanding geometric problem. The paper reaffirms the efficacy of Euclidean geometry in providing precise constructions and robust proofs for these angles, demonstrating the enduring strength of Euclidean principles from classical to modern times. The presented workflow goes beyond Euclidean geometry to examine non-Euclidean methods, particularly analytical approaches, revealing misconceptions that compromise the genetic and geometric rigor of Euclidean principles. The paper exposes incongruities when algebraic proofs related to angle constructability are applied to the Euclidean system, emphasizing the misalignment of fundamental geometric concepts. A notable result in the paper is the construction of a angle, introducing the “ angle chord” as a novel geometric property. This property challenges assumptions made by non-Euclidean methods and highlights the nuanced geometric properties crucial for rigorous constructions. The paper refutes the fallacy of relying solely on algebra for solutions to angles multiples of , emphasizing the necessity of embracing Euclidean geometry for geometric discoveries. The paper underscores the merits and resilience of Euclidean geometry, showcasing its independence and depth across historical and modern perspectives. The newly presented geometric construction not only resolves a longstanding question but also emphasizes the intrinsic strength and uniqueness of Euclidean principles in contrast to alternative methodologies.

In the advent of COVID-19 pandemic, testing is highly essential to be able to isolate, treat infected persons, and finally curb transmission of this infectious respiratory disease. Group testing has been used previously for various infectious diseases and recently reported for large-scale population testing of COVID-19. However, possible sample dilution as a result of large pool sizes has been reported, limiting testing methods’ detection sensitivity. Moreover, the need to sample all individuals prior to pooling overburden the limited resources such as test kits. An alternative proposed strategy where test is performed on pooled samples from individuals representing different households is presented here. This strategy intends to improve group testing method through the reduction in the number of samples collected and pooled during large-scale population testing. Moreover, it introduces database system which enables continuous monitoring of the population’s virus exposure for better decision making.

Adding zinc (II) and formate anions improves the thermal phase-stability of alpha-FAPbI3 materials and the spin-coated thin films of such doped FAPbI¬3 show an increased emission lifetime of up to 3.7 microsecond on quartz. This work investigates the effects of zinc and formate on the stability and time resolved photoluminescence of FAPbI3 perovskites for solar cell applications. Perovskite samples with varying concentrations of zinc and formate were made by incorporating different amounts of zinc formate and zinc iodide and characterized with XRD. Doping levels of 1.7% Zn(II) and 1.0% formate (relative to Pb) seem optimal. The thermal stability of the perovskite powders and thin films were assessed. XRD was virtually unchanged after 6 months. The time-resolved photo-luminescence spectroscopy of the doped spin-coated perovskite samples is reported. The results show that synergy between an anionic and a cationic dopant can take place, making the perovskite thermally more stable with a longer charge carrier lifetime.

Solid tumors universally possess the ability to evade contact inhibition of proliferation (CIP), a mechanism halting cell proliferation when cell-cell contacts occur. Merlin, an ERM-like protein, crucially regulates CIP and is frequently deactivated in various cancers, indicating its signifi-cance as a tumor suppressor in cancer biology. Despite extensive investigations into Merlin's role in cancer, its lack of intrinsic catalytic activity and frequent conformation changes has made it notoriously challenging to study. To address this challenge, we harnessed innovative luciferase technologies to create and validate a split-luciferase biosensor system. This system enables precise quantification of Merlin's conformation and activity both in vitro and within living cells. This biosensor significantly enhances the study of Merlin's molecular functions, serving as a potent tool to explore its contributions to CIP and tumorigenesis.

Background: This study delves into the examination of racial and ethnic disparities in the distribution of the Monkeypox (MPOX) virus vaccine within the United States, offering a critical healthcare perspective on an emerging public health concern. It particularly focuses on the demographic patterns associated with MPOX transmission and the allocation of vaccines. Methods: A comprehensive analysis was conducted, drawing on a wide array of data sources to understand the vaccine distribution and demographic trends in the United States. The study scrutinized three main aspects: MPOX cases by race and ethnicity, vaccine administration across different racial and gender categories, and the potential disparities therein. Results: The findings reveal significant disparities in the distribution of vaccine doses, with males, particularly gay, bisexual, and other Men who have sex with men (MSM), receiving the majority of doses. Moreover, substantial variations in MPOX cases are observed among different racial and ethnic groups, emphasizing the need for culturally sensitive public health strategies. Conclusions: The study underscores the urgent need for targeted public health interventions to address disparities and safeguard the well-being of those at higher risk, particularly MSM. It highlights the importance of equity in vaccine distribution and culturally sensitive approaches, and serves as a foundation for shaping effective public health policies and strategies to mitigate the spread of MPOX. This research advances our understanding of healthcare disparities in the context of an emerging viral infection, providing valuable insights for future public health initiatives.

The increasing concern regarding climate change continues to motivate research in the Arctic. Within the delicate cycle of the cryosphere, leads are an important kinematic feature that regulate heat balances in the Arctic. Therefore, it is necessary to quantify the genesis of leads over time to identify when and where changes are occurring. The use of a principal component analysis (PCA) is one such tool that is used to identify the characteristics of seasonal ice variability. The PCA not only identifies “normal” or “dominant” conditions or features, but also extract anomalous spatial features from an archive of long-term sequence of images.

The changes in consumer preferences and the increasingly competitive global market have demanded that food entrepreneurs engage in innovative value-added activities. The date is a delicatessen fruit known by its content of active compounds (e.g., dietary fiber and antioxidants) and its biological activity which has a vast potential in the design of new products such as bioactive ingredients, sugar substitutes, dietary supplements, functional foods, among others. In the current paper, innovative approaches to the value addition to date fruits and their processing by-products have been reviewed from recent high-quality scientific works. New processes such as ultrafiltration and hydrothermal treatments are shown as a useful alternative to obtain differentiated date-based ingredients (e.g., fiber concentrates, sap syrups, and date powders). Moreover, the use of date fruits and their byproducts as natural sources of value-added active compounds in the preparation of dairy, meat, and bakery and cereal products is also presented.

Mungbean [Vigna radiata (L.) Wilczek] in Australia has been transformed from a niche opportunistic crop into a major summer cropping option for dryland growers in the summer-dominant rainfall regions of Queensland and New South Wales. This transformation followed stepwise genetic improvements in both grain yields and disease resistance. For example, more recent cultivars such as ‘Crystal’, ‘Satin II’ and ‘Jade-AU‘ have provided up to a 20% yield advantage over initial introductions. Improved agronomic management to enable mechanised management and cultivation in narrow (<50 cm) rows has further promised to increase yields. Nevertheless, average yields achieved by growers for their mungbean crops remain less than 1 t/ha, and are much more variable than other broad acre crops. Further increases in yield and crop resilience in mungbean are vital. In this review, opportunities to improve mungbean have been analysed at four key levels including phenology, leaf area development, dry matter accumulation and its partitioning into grain yield. Improving the prediction of phenology in mungbean may provide further scope for genetic improvements that better match crop duration to the characteristics of target environments. There is also scope to improve grain yields by increasing dry matter production through the development of more efficient leaf canopies. This may introduce additional production risks as dry matter production depends on the amount of available water, which varies considerably within and across growing regions in Australia. Improving crop yields by exploiting photo-thermal sensitivities to increase dry matter is likely a less risky strategy for these variable environments. Improved characterisation of growing environments using modelling approaches could also better define and identify the risks of major abiotic constraints. This would assist in optimising breeding and management strategies to increase grain yield and crop resilience in mungbean for the benefit of growers and industry.

This study considers an application of the first-order Grey Markov Model to foresee the values of Italian power generation in relation to the available energy sources. The model is used to fit data from the Italian energy system from 2000 to 2022. The integration of Markovian error introduces a random element to the model, which is able now to capture inherent uncertainties and misalignments between the Grey model predictions and the real data. This application provides valuable insights for strategic planning in the energy sector and future developments. The results show good accuracy of the predictions, which provides powerful information for the effective implementation of energy policies concerning the evolution of energy demand in the country. Despite advancements, Italy’s 2032 energy mix will still significantly rely on fossil fuels, emphasizing the need for sustained efforts beyond 2032 to enhance sustainability.

Immune dysfunction has long been reported by medical professionals regarding astronauts suffering from opportunistic infections both during their time in space and a short time period afterwards once back on Earth. Various species of prokaryotes on board these space missions or cultured in a microgravity analogue exhibit increased virulence, enhanced formation of biofilms, and in some cases develop specific resistance for specific antibiotics. This poses a substantial health hazard to the astronauts confined in constant proximity to any present bacterial pathogens on long space missions with a finite number of resources including antibiotics. Furthermore, some bacteria cultured in microgravity develop phenotypes not seen in Earth gravity conditions, providing novel insights into bacterial evolution and research.

Voltage-gated Ca²⁺ (Ca_v) channels play pivotal roles in regulating gene transcription, neuronal excitability, and neurotransmitter release. In order to meet the spatial and temporal demands of visual signaling, Ca_v channels exhibit unusual properties in the retina compared to their counterparts in other areas of the nervous system. Here, we review current concepts regarding the specific subtypes of Ca_v channels expressed in the retina, their intrinsic properties and forms of modulation, and how their dysregulation could lead to retinal disease.

The Internet of Things (IoT) technology and devices constitute an exciting field in computer science that is rapidly emerging worldwide. IoT devices function by connecting real-world objects to the internet, resulting in a higher number of interconnected devices than ever witnessed in history. Through internet connectivity, these devices can be utilized in various ways, such as monitoring and tracking. Their prevalence is increasing exponentially, coinciding with advancements in wireless networking technologies. The internet’s enhanced connectivity has played a vital role in fostering the proliferation of IoT devices. Presently, almost any everyday object can be network-connected. The demand for automation and efficiency has also been a contributing factor to the advancements in this technology. This paper aims to review the emergence of IoT devices, analyze their common applications, and explore the future prospects in this promising field of computer science. The examined applications encompass healthcare, agriculture, and smart cities. Although IoT technology exhibits similar deployment trends, this paper will explore different fields to discern the subtle nuances that exist among them. IoT technology can be applied to nearly any domain, and each use case has unique requirements. To comprehend the future of IoT, it is essential to comprehend the driving forces behind its advancements in various industries. By gaining a better understanding of the emergence of IoT devices, readers will develop insights into the factors that have propelled their growth and the conditions that led to technological advancements. Moreover, a comprehensive understanding of the prevalent methodologies will enable readers to distinguish between current practices and future methods. Given the rapid rate at which IoT technology is advancing, this paper aims to provide researchers with an understanding of the factors that have brought us to this point and the ongoing efforts to shape the future of IoT.

We developed an amorphous solid dispersion (ASD) of the poorly water-soluble molecule niclosamide that achieved more than a 2-fold increase in bioavailability. Notably, this niclosamide ASD formulation increased the apparent drug solubility about 60-fold relative to the crystalline material due to the generation of nanoparticles. Niclosamide is a weakly acidic drug, BCS class II, and a poor glass former with low bioavailability in vivo. Hot-melt extrusion is a high-throughput manufacturing method commonly used in the development of ASDs for increasing the apparent solubility and bioavailability of poorly water-soluble compounds. We utilized the polymer polyvinylpyrrolidone–vinyl acetate (PVP–VA) to manufacture niclosamide ASDs by extrusion. Samples were analyzed based on their microscopic and macroscopic behavior and their intermolecular interactions, using DSC, XRD, NMR, FTIR, and DLS. The niclosamide ASD generated nanoparticles with a mean particle size of about 100 nm in FaSSIF media. In a side-by-side diffusion test, these nanoparticles produced a 4-fold increase in niclosamide diffusion. We successfully manufactured amorphous extrudates of the poor glass former niclosamide that showed remarkable in vitro dissolution and diffusion performance. These in vitro tests were translated to a rat model that also showed an increase in oral bioavailability.

In this review, we explore a broad-based view of technologies for supporting human activities on the Moon. Primarily, we assess the state of life support systems technology beginning with physicochemical processes, waste processing, bioregenerative methods, food production systems and the robotics and advanced biological technologies that support the latter. We observe that the Moon possesses in-situ resources but that these resources are of limited value in CELSS – indeed, CELSS technology is most mature in recycling water and oxygen, the two resources that are abundant on the Moon. This places a premium on developing CELSS that recycles other elements that are rarified on the Moon including C and N in particular but also other elements such as P, S and K which might be challenging to extract from local resources. Although we focus on closed loop ecological life support systems, we also consider related technologies that involve the application of biological organisms to bioregenerative medical technologies and bioregenerative approaches to industrial activity on the Moon as potential future developments.

The paper briefly reviews the Clifford algebras of space Cl(3,0) and anti-space Cl(0,3) with a particular focus on the paravector representation, emphasizing the fact that both algebras have an isomorphic center represented just by two coordinates. Since the paravector representation allows assigning the scalar element of grade 0 to the time coordinate, we consider the relativity in such two-dimensional spacetime for a uniformly accelerated frame with the constant acceleration 3Hc. Using the Rindler coordinate transformations in two-dimensional spacetime and then applying it to Minkowski coordinates, we obtain the FLRW metric, which in the case of the Clifford algebra of space Cl(3,0) corresponds to the anti-de Sitter (AdS) flat (k=0) case, the negative cosmological term and an oscillating model of the universe. The approach with anti-Euclidean Clifford algebra Cl(0,3) leads to the de Sitter model with the positive cosmological term and the exact form of the scale factor used in modern cosmology.

A novel effective vibrational mode was discovered in the conventional transducer with an array of orthogonal (square) regular piezoelectric rods in 1-3 piezocomposite, containing the damping backing and front matching layers. The operational resonance in the structure was determined as the Surface Acoustic Wave (SAW) on the backing boundary excited by the adjacent piezo-rods, with its frequency typically near 3 times lower the fundamental half-lambda conventional piezocomposite resonance. Pulse-echo sensitivity and transmitting sound-pressure-level (SPL) in air showed that the signal strength is roughly comparable to the industrial similar air transducers at the frequency range 100…700 kHz, where at these frequencies the lateral and longitudinal piezoelement dimensions in the conventional transducer design are typically close to each other causing interference with unwanted coupling modes. As was determined theoretically and proved in experiments, the backing SAW resonance effect in the transducer performance is inherent just to the regular periodic 1-3 piezocomposite structure, and does occur neither with randomly located/oriented piezo-rods, nor in the homogeneous piezo-plate at least with the same lateral cross-section as the connected to it backing. The purpose of the article is to investigate a newly discovered operational vibrational mode of a SAW type in 1-3 regular piezocomposite, other than piezoelectric resonance. The investigated phenomena can improve the transceiver sensitivity, bandwidth, providing lower drive voltage, and smaller and lighter weight ultrasonic transducers. Based on the piezocomposites with thickness’ 1…1.5 mm (rod resonance near 2…3 MHz), pillar width 0.2…0.8 mm, kerf width 0.1…0.4 mm, the transceivers with an operating frequency from 140 kHz to 650 kHz were designed and fabricated with a conventional backing of a mixture of high-density tungsten powder and epoxy, and a matching layer of a mixture of low-density glass bubbles and epoxy. Experimental evaluation of their acoustical performance showed expected characteristics suitable for practical applications.

The exact etiology of myopia remains elusive. The author proposes the particle property of photon in living tissue and the photon-electron theory in living tissue, if the frequency of the photon exceeds the threshold, the photon has enough energy to strike the electron away and forms a hole of a diameter in photon diameter scale in living tissue include the eye. Longer time of high-frequency electromagnetic radiation will cause more holes and a larger radius of holes. The visual light which passes through the radiated hole in the eye cannot be refracted on the macula, this is myopia symptom of blurred vision, shortening the distance of the eye and the object will include more visual light into cornea and lens, this is myopia another symptom of nearsightedness. The particle property of photon causes elongation of the eye and the macular holes.Blue light and X-ray are two kinds of high-frequency electromagnetic radiation which can shot holes in eye and cause myopia.

The electric field is enormously more powerful than the gravitational field. However, in our normal experience there is no electric field, the electric force is missing. How is it that when you get to larger and larger scales the gravitational field is extremely important whereas the electric field becomes less and less important [1]? This paper proposes a model to explain why gravitation dominates at a larger scale.

Untargeted metabolomics is a powerful tool for measuring and understanding complex biological chemistries. However, employment, bioinformatics and downstream analysis of mass spectrometry (MS) data can be daunting for inexperienced users. Numerous open-source and free-to-use data processing and analysis tools exist for various untargeted MS approaches, including liquid chro-matography (LC), but choosing the ‘correct’ pipeline isn’t straight-forward. This tutorial, in con-junction with a user-friendly online guide presents a workflow for connecting these tools to process, analyse and annotate various untargeted MS datasets. The workflow is intended to guide explor-atory analysis in order to inform decision-making regarding costly and time-consuming down-stream targeted MS approaches. We provide practical advice concerning experimental design, organisation of data and downstream analysis, and offer details on sharing and storing valuable MS data for posterity. The workflow is editable and modular, allowing flexibility for updated/ changing methodologies and increased clarity and detail as user participation becomes more common. Hence, the authors welcome contributions and improvements to the workflow via the online repository. We believe that this workflow will streamline and condense complex mass-spectrometry approaches into easier, more manageable, analyses thereby generating opportunities for researchers previously discouraged by inaccessible and overly complicated software.

Background: Cell proliferation and the cell cycle are fundamental to tumor development, with mitosis playing a crucial role in cell division. Understanding the complexities of the cell cycle and mitosis is critical for cancer research, especially in the context of developing therapeutic strategies. Objective: This review highlights mitotic poisons as potential anti-cancer pharmacotherapeutics, particularly their structural and functional group diversity presenting opportunity for semi-synthesis of new derivatives with multi-target mechanisms relevant for cancer pharmacotherapeutics. Also, the review explores naturally occurring mitotic poisons and inhibitors of microtubule-dependent molecular motors as promising cancer pharmacotherapeutics. Methods: A comprehensive review of literature from 2004 to 2023 was conducted, covering studies on cell proliferation, mechanism of cell cycle regulation, mitosis, cytokinesis, and anti-cancer drug development. The published literature was collected primarily from PubMed, Scopus, Medline, Web of Science Core Collections, Google Scholar and other relevant scientific databases using keywords including but not limited to mitotic poisons and cancer, sources of mitotic poisons, mechanism of mitotic poisons, targets of mitotic poisons and structural diversity of mitotic poisons. The efficacy and limitations of various mitotic poisons and their impact on different cancer types were examined. Recent advancements in targeted therapeutic interventions for various cancers were also explored. Results: The effectiveness and limitations of mitotic poisons, including Taxanes, Epothilones, Colchicine, Vinca alkaloids, Berberine, Laulimalide, and Pseudolaric acid B, were highlighted. Drugs targeting mitotic kinases such as CDKs, Aurora kinases, PLK1, and WEE1 inhibitors were reported. Inhibiting kinesin motor proteins such as Eg5 and KIF15 to interfere with spindle formation and cell division were discussed, along with specific genomic alterations in KIF genes and the discovery of KIFC1 as potential for future research and drug development. Conclusion: Targeting microtubules and mitotic kinases, along with inhibiting kinesin motor proteins, show promise for cancer pharmacotherapeutics. The combination of targeted therapies, patient stratification based on biomarkers (such as low alpha-1 acid glycoprotein and high p63 expression), and exploration of alternative natural sources of mitotic poisons and analogues can significantly advance cancer pharmacotherapy to improve patient outcomes.

There is a growing notion that biomass are the best resource to replace the declining fossil fuels, yet both share the long lived human threat: toxic combustion emissions. Among the toxic combustion products is carbon monoxide (CO) that not only causes acute but also chronic ailments. This brief review discusses the solid fuel processing technologies from combustion, thermochemical and biochemical processing to kinetics and thermodynamics including the mechanism for release of CO. It further expounds on the burden that CO has caused England and Wales in the last 25 years. The main gist are the systems that have been developed to minimize human exposure to CO including cooking, heating, catalytic and detection systems. Finally, alternative technologies are discussed that work by changing the chemical nature of solid fuels as a way to minimize CO emissions.

Natural cycles underpin the very stuff of life. In this commentary we consider unnatural cycles: that is, anthropogenic activities which have a circularity, but whose nature is to have a detrimental effect on human health, exacerbating existing problems. Natural cycles have feedback loops, some of which have recently come to light, with an understanding that everything is connected in some way. In health, feedback loops are imperative in homeostatic mechanisms. However, in the unnatural cycle the feedback loops serve to reinforce (and in some cases amplify) negative problems. We offer a commentary on an unnatural cycle moving from air quality to lung function and back to air quality; we call this the lung disease unnatural cycle. We suggest where links occur, and where wider consideration of interactions between various disciplines can lead to breaking this unnatural (or vicious) cycle, changing it to a healthy cycle where individual health can be improved, along with better global scale outcomes. We suggest that many activities within this unnatural cycle occur within silos. However, the improved cycle incorporates joint activities at geological, health, and financial levels, to the mutual benefit of all, breaking the unnatural cycle, and improving health, life and financial costs.

Nowadays, diamonds are widely used in science and technology. However, the properties of diamonds due to their defects are not fully understood. In addition to optical methods, positron annihilation spectroscopy (PAS) can be successfully used to study defects in diamonds. Positrons are capable of detecting vacancies, small and large clusters of vacancies induced by irradiation, by providing information about their size, concentration, and chemical environment. By mapping in the infrared (IR) range, it is possible to consider the admixture composition of the main inclusions of the whole plate. The article presents the results of the study of defects in synthetic diamond plates, one of which was irradiated by electrons. Presents data about the distribution of the defect concentration obtained by Infrared spectroscopy. PAS with a monochromatic positron beam can be used as a non-destructive technique of detecting defects (vacancy) distribution over the depth of diamond plates.

In order to reach the theoretical efficiency limits of lead-based metal halide perovskite solar cells, the voltage should be enhanced because it suffers from nonradiative recombination. Perovskite materials contain intrinsic defects that can act as Shockley-Read-Hall recombination centers. Several experimental and computational studies have characterized such defect states within the band gap. We give a systematic overview of compositional engineering by distinguishing the different defect reducing mechanisms. Doping effects are divided into influences on: (1) Crystallization; (2) Lattice properties. Incorporation of dopant influences the lattice properties by: (a) Lattice strain relaxation; (b) Chemical bonding enhancement; (c) Band gap tuning. The intrinsic lattice strain in undoped perovskite was shown to induce vacancy formation. The incorporation of smaller ions, such as Cl, F and Cd, increases the energy for vacancy formation. Zn doping is reported to induce strain relaxation but also to enhance the chemical bonding. The combination of computational studies using (DFT) calculations quantifying and qualifying the defect reducing propensities of different dopants with experimental studies is essential for deeper understanding and unraveling insights, such as the dynamics of iodine vacancies and the photochemistry of the iodine interstitials, and can eventually lead to a more rational approach in the search for optimal photovoltaic materials.

More water utilities are adopting Aquifer Storage and Recovery (ASR) to balance long-term water supply and demand. Due to large implementation and operation costs, ASR projects need to be optimized, particularly for energy use, which is a major operating expense. This study examines the relationships among energy use, recharge, and recovery at two ASR projects in the western United States. The major finding is an economy of scale for recovery processes, but not for gravity-fed recharge processes. The economy of scale found is as follows: the energy intensity recovered decreases with volume. This suggests it is more energy-efficient to recover large volumes of water in one interval instead of recovering smaller volumes at more frequent intervals. The H2Oaks recovery process experienced a 78% decrease in energy intensity from 0 to 50,000 m3 recovered, while the Sand Hollow site experienced a 43% decrease in energy intensity from 0 to 50,000 m3 recovered. Statistical analyses of the recovery process showed p values lower than 0.0001, R2 values between 0.43 and 0.57, and a RMSE value between 0.55 and 2.1, indicating the presence of a moderate correlation between energy and volume. This economy of scale has been observed in multiple instances in water and wastewater treatment. This finding not only has applications to ASR but also all recovery or recharge wells, whether or not they are paired with each other. Furthermore, this study confirms the need for more reliable and accessible energy data to fully understand the implications of the energy–water nexus.

Next-generation sequencing is now a mature technology, allowing partial animal genomes to be produced for many clades. Though many software exist for genome assembly and annotation, a simple pipeline that allows researchers to input raw sequencing reads in fastq format and allow the retrieval of a completely assembled and annotated mitochondrial genome is still missing. mitoMaker 1.0 is a pipeline developed in python that implements (i) recursive de novo assembly of mitochondrial genomes using a set of increasing k-mers; (ii) search for the best matching result to a target mitogenome and; (iii) performs iterative reference-based strategies to optimize the assembly. After (iv) checking for circularization and (v) positioning tRNA-Phe at the beginning, (vi) geneChecker.py module performs a complete annotation of the mitochondrial genome and provides a GenBank formatted file as output.

Genomic medicine is moving from research to the clinic. There is a lack of evidence about the impact of genomic medicine interventions on health outcomes. This is due in part to a lack of standardized outcome measures that can be used across different programs to evaluate the impact of interventions targeted to specific genetic conditions. The eMERGE Outcomes working group (OWG) developed measures to collect information on outcomes following the return of genomic results to participants for several genetic disorders. These outcomes were compared to outcome intervention pairs for genetic disorders developed independently by the ClinGen Actionability working group (AWG). In general, there was concordance between the defined outcomes between the two groups. The ClinGen outcomes tended to be higher level and the AWG scored outcomes represented a subset of outcomes referenced in the accompanying AWG evidence review. eMERGE OWG outcomes were more detailed and discrete, facilitating collection of relevant information from health records. This paper demonstrates that common outcomes for genomic medicine interventions can be identified. Further work is needed to standardize outcomes across genomic medicine implementation projects and make these publicly available to enhance dissemination and assist in making precision public health a reality.

The Golden ratio is an irrational number that has a tendency to appear in many different scientific and artistic fields. It may be found in natural phenomena across a vast range of length scales; from galactic to atomic. In this review, the mathematical properties of the Golden ratio are discussed before exploring where in nature it has been found; beginning at astronomical scales and progressing to smaller lengths, until reaching those of atomic and quantum physics. In making such a tour across length scales, it is illustrated just how prevalent this single number is within the natural universe.

Simulating the non-perturbative and non-Markovian dynamics of open quantum systems is a very challenging many body problem, due to the need to evolve both the system and its environments on an equal footing. Tensor network and matrix product states (MPS) have emerged as powerful tools for open system models, but the numerical resources required to treat finite temperature environments grow extremely rapidly and limit their applications. In this study we use time-dependent variational evolution of MPS to expore the striking theory of Tamescelli et al. that shows how finite temperture open dyanmics can be obtained from zero temperature, i.e. pure wave function, simulations. Using this approach, we produce a benchmark data set for the dynamics of the Ohmic spin-boson model across a wide range of coupling and temperatures, and also present detailed analysis of the numerical costs of simulating non-equilibrium steady states, such as those emerging from the non-perturbative coupling of a qubit to baths at different temperatures. Despite ever growing resource requirements, we find that converged non-perturbative results can be obtained, and we discuss a number of recent ideas and numerical techniques that should allow wide application of MPS to complex open quantum systems.

With rapid advances in gene editing and gene therapy technologies, the development of genetic, cell, or protein-based cures to disease are no longer the realm of science fiction but that of today’s practice. The impact of these technologies are rapidly bringing them to the veterinary market as both enhanced therapeutics and towards modeling their outcomes for translational application. Simply put, gene editing enables scientists to modify an organism’s DNA a priori through the use of site-specific DNA targeting tools like clustered regularly interspaced short palindromic repeats and CRISPR-associated protein 9 (CRISPR/Cas9). Gene therapy is a broader definition that encompasses the addition of exogenous genetic materials into specific cells to correct a genetic defect. More precisely, the U.S Food and Drug Administration (FDA) defines gene therapy as “a technique that modifies a person’s genes to treat or cure disease” by either (i) replacing a disease-causing gene with a healthy copy of the gene; (ii) inactivating a disease-causing gene that was not functioning properly; or (iii) introducing a new or modified gene into the body to help treat a disease. In some instances, this can be accomplished through direct transfer of DNA or RNA into target cells of interest or more broadly through gene editing. While gene therapy is possible through the simple addition of genetic information into cells of interest, gene editing allows the genome to be reprogrammed intentionally through the deletion of diseased alleles, reconstitution of wild type sequence, or targeted integration of exogenous DNA to impart new function. Cells can be removed from the body, altered, and reinfused, or edited in vivo. Indeed, manufacturing and production efficiencies in gene editing and gene therapy in the 21^st century has brought the therapeutic potential of in vitro and in vivo reprogrammed cells, to the front lines of therapeutic intervention (Brooks et al., 2016). For example, CAR-T cell therapy is revolutionizing hematologic cancer care in humans and is being translated to canines by us and others, and gene therapy trials are ongoing for mitral valve disease in dogs.

Tungsten carbide inserts (TCI) and polycrystalline diamond compact (PCD) cutters used in two types of drill bits for drilling oil and gas wells were evaluated by a pin-on-disc test. The morphology of the worn surface was characterized by scanning electron microscopy (SEM). The behavior of corrosion resistance was evaluated with the electrodynamic polarization technique. The polycrystalline diamond compact cutter has a higher hardness, better corrosion, and wear behavior compared to tungsten carbide.

Older adults (age ≥65) are at high risk of influenza morbidity and mortality. This study evaluated the impact of a hypothetical two-dose influenza vaccine regimen per season to reduce symptomatic flu cases by providing preseason (first dose) and mid-season (second dose) protection to offset waning vaccine effectiveness (VE). The Framework for Reconstructing Epidemiological Dynamics (FRED), an agent-based modeling platform, was used to compare typical one-dose vaccination to a two-dose vaccination strategy. Primary models incorporated waning VE of 10% per month and varied influenza season timing (December through March) to estimate cases and hospitalizations in older adults. Additional scenarios modeled reductions in uptake and VE of the second dose, and overall waning. In seasons with later peaks, two vaccine doses had the largest potential to reduce cases (14.4% with February peak, 18.7% with March peak) and hospitalizations (13.1% with February peak, 16.8% with March peak). Reductions in cases and hospitalizations still resulted but decreased when 30% of individuals failed to receive a second dose, second dose VE was reduced, or overall waning was reduced to 7% per month. Agent-based modeling indicates that two influenza vaccine doses could decrease cases and hospitalizations in older individuals. The highest impact occurred in the more frequently observed late-peak seasons. The beneficial impact of the two-dose regimen persisted despite model scenarios of reduced uptake of the second dose, decreased VE of the second dose, or overall VE waning.

In this work, we present some results related with the issue of the Loop Quantum Black Holes (LQBH) thermodynamics by the use of the tunneling radiation formalism. The information loss paradox is also discussed in this context, where we have considered the influence of back reaction effects.

Evidence shows that weightloss improves insulin sensitivity but few studies have examined the effect of macronutrient composition independently of weight loss on direct measures of insulin sensitivity. We randomised 89 overweight or obese women to either a standard diet (StdD) that was intended to be low in fat and relatively high in carbohydrate (n=42) or to a relatively high protein (up to 30% of energy), relatively high fibre (>30g/day) diet (HPHFib) (n=47) for 10 weeks. Advice regarding strict adherence to energy intake goals was not given. Insulin sensitivity and secretion was assessed by a novel method - the Dynamic Insulin Sensitivity and Secretion Test (DISST). Although there were significant improvements in body composition and most cardiometabolic risk factors on HPHFib, insulin sensitivity was reduced by 19.3% (95% CI: 31.8, 4.5%; p=0.013) in comparison with StdD. We conclude that the reduction in insulin sensitivity after a diet relatively high in both protein and fibre, despite cardiometabolic improvements, suggests insulin sensitivity may reflect metabolic adaptations to dietary composition for maintenance of glucose homeostasis, rather than impaired metabolism.

Views of fire in the contemporary physical sciences arguably accord with Heraclitus’ proposal that ‘all things are an exchange for fire, and fire for all things, as goods for gold and gold for goods.’ Fire is a media, as John Durham Peters has stated, a species of transformative biochemical reactions between the flammable gases found in air, such as oxygen, and those found in fuels, such as plants. Inspired by an ignition source, these materials react and transform themselves and their surrounds into light and heat energy, carbon dioxide, water vapour, char and much else besides. Fire is conjunctural, durational and transformative. Fire is a dialectician, at once consuming living and dead organic matter and providing both the space and ingredients for new and renewed organic life. In this article, we consider the diverse ways in which fire is today framed as a social problem, an ecological process, an ancient tool, a natural disaster, a source of economic wealth and much more. In this way, we seek to explore the value and limits of ‘elemental thinking’ in relation to the planetary predicaments described by ‘the Anthropocene’.

Candida albicans as an opportunistic pathogen exploits the host immune system and causes a variety of life-threatening infections. The polymorphic nature of this fungus gives it tremendous advantage to breach mucosal barriers and cause a variety of oral and disseminated infections. Enterococcus faecalis, another opportunistic pathogen co-exists with C. albicans in several niches in the human body, including the oral cavity and gastrointestinal tract. However, interactions between E. faecalis and C. albicans on oral mucosal surfaces remain unknown. Here, for the first time, we comprehensively characterized the interactive profiles between laboratory and clinical isolates of C. albicans (SC5314 and BF1) and E. faecalis (OG1RF and 846) on an organotypic oral mucosal model. Our results demonstrated that the two species formed robust biofilms on the mucosal tissue surface with profound surface erosion and fungal invasion. Specifically, this effect was more pronounced in the laboratory isolates than in the clinical isolates. Notably, several genes of C. albicans involved in tissue adhesion, hyphal formation, fungal invasion, and biofilm formation were significantly upregulated in the presence of E. faecalis. This study highlights the strain-dependent cross-kingdom interactions between E. faecalis and C. albicans on oral mucosa, demonstrating the requisite to study more substrate-dependent polymicrobial interactions.

Community peer review is a method that extends the ethics of consent into scientific practices. It gives communities affected by scientific research the ability to determine whether research may cause them harm and be part of determining how knowledge should best circulate to reduce or eliminate that harm. This paper introduces the method of community peer review by first looking at the concepts of consent and refusal, then outlining the steps to community peer review, using a case study of community meetings on a study of plastic ingestion by fish to elucidate the details of each step. Steps include: hiring a community member to the team; researching the social, cultural, and economic contexts of the community; identify the community; ensure skills for community conversation are in place; call the community meeting; conduct the community meeting; and analyze feedback for consent and refusal. Community peer review is premised on the idea that research is not inherently good and can cause harm, and that the best people to know whether and what kinds of harms are likely to occur are community members rather than researchers. The second premise is that the researcher’s “right” to research never supersedes a community’s right to not be harmed.

Background: Advances in additive manufacturing and the development of antimicrobial biopolymers facilitate the production of critical medical devices with strong and safe biocidal properties. The purpose of this study was to assess the antimicrobial efficacy, safety, and longevity of a polylactic acid-based biopolymer supplemented with a copper-based composite additive. Methods: An antimicrobial polylactic acid-based biopolymer was tested against several inoculants including Staphylococcus Aureus, MRSA, E. coli, Listeria, HCoV-229E (a SARS-CoV-2 surrogate), and HIV-1. Material safety was evaluated according to international testing standards for in vitro cytotoxicity. Results: The main findings of the present investigation showed a strong and long-lasting biocidal effect of a polylactic acid-based biopolymer embedded with a copper-based composite additive against Staphylococcus Aureus, MRSA, E. coli, Listeria, HCoV-229E (a SARS-CoV-2 surrogate), and HIV-1. Furthermore, the cytotoxicity and safety assessment of the antimicrobial biopolymer was found to be “non-toxic” and safe for human skin contact. Conclusions: The present investigation showed that the antimicrobial biopolymer exhibits strong and long-lasting biocidal properties against an array of viral and bacterial inoculants.

Targeted enrichment of ultraconserved elements (UCE) has emerged as a promising tool for inferring evolutionary history in many taxa, with utility ranging from phylogenetic and phylogeographic questions at deep time scales to population level studies at shallow time scales. However, the methodology can be daunting for beginners. Our goal is to introduce UCE phylogenomics to a wider audience by summarizing recent advances in arthropod research, and to familiarize readers with background theory and steps involved. We define terminology used in association with the UCE approach, evaluate current laboratory and bioinformatic methods and limitations, and, finally, provide a roadmap of steps in the UCE pipeline to assist phylogeneticists in making informed decisions as they employ this powerful tool. By facilitating increased adoption of UCE in phylogenomics studies that deepen our comprehension of the function of these markers across widely divergent taxa, we aim to ultimately improve understanding of the arthropod tree of life.

The power system has rapidly grown and expanded over the past decades and has been experiencing major changes and challenges. The increase in energy demand and the modern advancements in the smart grid, such as solar and wind energies and electric vehicles, have led to complexity and complications for utilities. A further layer of complexity and difficulty was added by the rapid expansion of behind-the-meter (BTM) photovoltaic (PV) systems with various designs and characteristic features. The rapid increase and the invisible solar power (BTM) have led to fluctuations in power grid stability and reliability and to inefficiency. Accurate forecasting of load generation will help to assure optimal planning, minimize the negative effects of the PV systems, and minimize the operational and maintenance costs. The authors propose a solution that uses combinations of K-means clustering with neural network machine learning models, AMI real-world PV load generation, and weather data to forecast the generation load at customer locations to achieve a 2.49% error between actual and predicted generation load.

Grill-specific footprints for common fuels/grill types in the USA are estimated from public information and data from a major grill manufacturer. These are a function of both 1) a fuel’s footprint and 2) a grill’s efficiency of cooking. In 2022, grill-specific footprints vary by 9:1. A typical gas grill is highest at 3.6 lb CO2e/grill session, nine times that of a wood-pellet grill, lowest at 0.4 lb. Charcoal briquettes, electricity and super-efficient gas grills come in-between. Pellets are lowest, because they are made from waste wood and their production burden is modest. Electricity has the highest fuel footprint, yet the second-lowest grill-specific footprint, thanks to its high efficiency. Briquettes come in fourth, because their production involves fossil gas, and they contain some fossil coal. Grill efficiency is key for gas (natural gas or propane): a typical gas grill has twice the footprint of a super-efficient one. In 2027, with bio substitution, the super-efficient gas grill would move ahead of pellets. Electricity and charcoal could improve but would still place fifth and sixth. The range of grill-specific footprints could fall to 4.5:1, within a much-lower range, the highest footprint in 2027 almost 60% lower than 2022’s highest.

The late universe contains a wealth of information about fundamental physics and gravity, wrapped up in non-Gaussian fields. To make use of as much information as possible it is necessary to go beyond two-point statistics. Rather than going to higher order N-point correlation functions, we demonstrate that the probability distribution function (PDF) of spheres in the matter field (a one-point function) already contains a significant amount of this non-Gaussian information. The matter PDF dissects different density environments which are lumped together in two-point statistics, making it particularly useful for probing modifications of gravity or expansion history. Our approach in Cataneo et. al. 2021 extends the success of Large Deviation Theory for predicting the matter PDF in ΛCDM in these “extended” cosmologies. A Fisher forecast demonstrates the information content in the matter PDF via constraints for a Euclid-like survey volume combining the 3D matter PDF with the 3D matter power spectrum. Adding the matter PDF halves the uncertainties on parameters in an evolving dark energy model, relative to the power spectrum alone. Additionally, the matter PDF contains enough non-linear information to substantially increase the detection significance of departures from General Relativity, with improvements up to six times the power spectrum alone. This analysis demonstrates that the matter PDF is a promising non-Gaussian statistic for extracting cosmological information, particularly for beyond ΛCDM models.

Here we introduce Literature Mapper, a Python QGIS plugin that provides a method for creating a spatial bibliography manager as well as a specification for storing spatial data in a bibliography manager. Literature Mapper uses QGIS’ spatial capabilities to allow users to add location information to a Zotero library, a free and open source bibliography manager. Literature Mapper enhances the citations in a user’s online Zotero database with geo-locations by storing spatial coordinates as part of traditional citation entries. Literature Mapper receives data from and sends data to the user’s online database via Zotero’s web API. By using Zotero as the backend data storage, Literature Mapper benefits from all of its features including shared citation Collections, public sharing, and an open web API usable by additional applications, such as web mapping libraries. We evaluate Literature Mapper’s ability to provide insights into the spatial distribution of published literature by mapping the study sites described in academic publications related to California’s coastal strand vegetation. The results of this exercise are presented in static and web map form.

Lanthanide ion doped upconversion nanoparticles (UCNPs) that can convert low-energy infrared photons into high-energy visible and ultraviolet photons, are becoming highly sought-after for advanced biomedical and biophotonics applications. Their unique luminescent properties enable UCNPs to be applied for diagnosis, including biolabeling, biosensing, bioimaging and multiple imaging modality, as well as therapeutic treatments including photothermal and photodynamic therapy, bio-reductive chemotherapy and drug delivery. For the employment of the inorganic nanomaterials into biological environment, it is critical to bridge the gap in between nanoparticles and biomolecules via surface modifications and subsequent functionalisation. This work reviews the various ways to surface modify and functionalise UCNPs so as to impart different functional molecular groups to the UCNPs surfaces for a board range of applications in biomedical areas. We discussed commonly used base functionalities, including –COOH, -NH2 and –SH, that are typically imparted to UCNP surfaces so as to provide further functional capacity.

Background: Neurological disorders are the leading cause disability in Australia and the world. Combating the perceived difficulty of neurology or “neurophobia” and improving physician education is a key component in addressing this problem. We aim to conduct the first study to identify whether neurophobia exists in medical students and junior doctors in an Australian population and try to identify factors that may contribute to this in this population. Methods: A 24 question online validated survey was distributed via email broadcast to all medical students and junior doctors at a metropolitan tertiary care centre in Australia. Responses were collected over 6 weeks with weekly reminder emails for 4 weeks after the initial invitation email. Results: 114 medical students and junior doctors participated in the study. Participants perceived neurology as the most difficult medical speciality compared to 10 other medical specialties (p=0.001). The top three factors contributing to this perceived difficulty were: a lack of understanding of neuroanatomy, lack of diagnostic certainty and lack of clinical exposure. 65% of the participants stated that they had too little planned teaching in neurology with only 36% of the participants having performed a neurology rotation during medical school. Conclusion: The prevalence of neurophobia in this Australian cohort of medical students and junior doctors is consistent with previous findings from around the world. This concerning finding requires further examination into the contributing factors in order to created trials of targeted interventions in order to resolve this.

Increased soluble endoglin (sENG) were observed in human brain arteriovenous malformations (bAVMs), and overexpression of sENG with vascular endothelial growth factor (VEGF)-A induced dysplastic vessel formation in mouse brain. However, the underlying mechanism of sENG-induced vascular malformations is not clear. While evidence suggests the role of sENG as a pro-inflammatory modulator, increased microglial accumulation and inflammations were observed in bAVMs. Therefore, we hypothesized that microglia mediate sENG-induced inflammation and endothelial cell (EC) dysfunction in bAVMs. In this study, we confirmed that sENG with VEGF-A overexpression induced dysplastic vessel formation. Remarkably, there were increased microglial activation around dysplastic vessels with expression of NLRP3, inflammasome marker. We found that sENG increased the gene expression of VEGF-A, pro-inflammatory cytokines/inflammasome mediators (TNF-α, IL-6, NLRP3, ASC, Caspase-1, and IL-1β), and proteolytic enzyme (MMP-9) in BV2 microglia. The conditioned media from sENG-treated BV2 (BV2-sENG-CM) significantly increased angiogenic factors (Notch-1 and TGFβ) and pERK1/2 in ECs while it decreased IL-17RD, an anti-angiogenic mediator. Finally, the BV2-sENG-CM significantly increased EC migration and tube formation. Together, our study demonstrates that sENG provokes microglia to release angiogenic/inflammatory responses which may be involved in EC dysfunction. Our study suggests the contribution of microglia in the pathology of sENG-associated vascular malformations.

Food insecurity is a pervasive issue for Allegheny County as one in five residents experience food insecurity. Food insecurity is linked to chronic health conditions like heart disease and hypertension and disproportionately affects women in the United States, particularly women who are head of household. There are multiple dimensions used to measure regional food insecurity, one of which is food accessibility. Prior research has examined the linkages between food access and food insecurity, and this study aims to further explore the relationship between equitable access to sustainable food and levels of regional food insecurity. This study examines food outlets in Allegheny County to determine if there is a significant relationship between food outlet availability and food insecurity. Both the presence and accessibility of these food outlets were examined. To measure accessibility, the walking distance to the nearest public transportation stop was calculated for each public transportation stop. The minimum distance to each food outlet was compared to food insecurity rates on a Census Tract level. Results showed that communities without grocery stores did, on average, have higher rates of food insecurity. Also, communities with a higher proportion of female-headed households experienced greater food insecurity, regardless of access to food outlets. However, there was no statistically significant relationship between the distance from public transportation stops to grocery stores and rates of food insecurity. Based on these findings, we suggest that sole reliance on distance as an indicator of food insecurity can be misleading, and there should be a greater focus on walkability within the community as using opposed to physical distance alone.

Human ether-a-go-go-related gene (hERG) potassium channel is well-known contributor to drug-induced cardiotoxicity and therefore an extremely important target when performing safety assessments of drug candidates. Ligand-based approaches in connection with quantitative structure active relationships (QSAR) analyses have been developed to predict hERG toxicity. Availability of the recent published cryogenic electron microscopy (cryo-EM) structure for the hERG channel opened the prospect for using structure-based simulation and docking approaches for hERG drug liability predictions. In recent time, the idea of combining structure- and ligand-based approaches for modeling hERG drug liability has gained momentum offering improvements in predictability when compared to ligand-based QSAR practices alone. The present article demonstrates uniting the structure-based SILCS (site-identification by ligand competitive saturation) approach in conjunction with physicochemical properties to develop predictive models for hERG blockade. This combination leads to improved model predictability based on Pearson’s R and percent correct (represents rank-ordering of ligands) metric for different validation sets of hERG blockers involving diverse chemical scaffold and wide range of pIC50 values. The inclusion of the SILCS structure-based approach allows determination of the hERG region to which compounds bind and the contribution of different chemical moieties in the compounds to blockade, thereby facilitating the rational ligand design to minimize hERG liability.

Cognitive scientists have paid very little attention to magic as a distinctly human activity capable of creating situations or events that are considered impossible because they violate expectations and conclude with the apparent transgression of well-established cognitive and natural laws. And even though magic techniques appeal to all known cognitive processes from sensing, attention and perception to memory and decision making, the relation between science and magic has so far been mostly unidirectional, with the primary goal of unraveling how magic works. Building up from the deconstruction of a classic magic trick, we provide here a cognitive foundation for the use of magic as a unique and largely untapped research tool to dissect cognitive processes in tasks arguably more natural than those usually exploited in artificial laboratory settings. Magicians can submerge every spectator into the precise experimental protocol they have previously designed, accounting with ease for both circumstantial and social contexts. Magicians do not base the success of their experiments in statistical measures that smear out the individual in favor of an average spectator that we know never exists in the real world. They target each and everyone in the audience and, often, with a complete accomplishment. Magicians deliver their cognitive manipulations in real-time, in tight closed-loop with the audience, and in a single trial (they cannot afford to repeat the trick if it fails). Magic has also an inherent and strong social component, merging the private cognitive processes of each spectator with the group dynamics. Finally, when combined with the wide range of precise measuring and wearable technologies available today, magic paves the way for a road not taken towards real-world cognitive science. We dare to speculate that some of the mysteries of how the brain works may be trapped in the split realities present in each magic effect.

We examine the nonequilibrium production of topological defects -- braids -- in semiflexible filament bundles under cycles of compression and tension. During these cycles, the period of compression facilitates the thermally activated pair production of braid/anti-braid pairs, which then may separate when the bundle is under tension. As result, appropriately tuned alternating periods of compression and extension should lead to the proliferation of braid defects in a bundle so that linear density of these pairs far exceeds that expected in thermal equilibrium. Secondly, we examine the slow extension of braided bundles under tension, showing that their end-to-end length creeps nonmonotonically under a fixed force due to braid deformation and the motion of the braid pair along the bundle. We conclude with a few speculations regarding experiments on semiflexible filament bundles and their networks.

The universal Debye – Mayer – Kelly hybrid model was proposed for the description of the heat capacity from 0 K to the melting points of substance within the experimental uncertainty for the first time. To describe the heat capacity, the in-house software on the base of commercial one DELPHI-7 was used with a 95% confidence level. To demonstrate the perfect suitability of this model, a thermodynamic analysis of the heat capacities of the fourth group elements, and some compounds of the A^IIIB^V and A^IIB^VI phases was carried out. It produced good agreement within the experimental uncertainty. There is no a similar model description in literature.The Similarity Method is a convenient and effective tool for critical analysis of the heat capacities of isostructural phases, which was used as an example for diamond-like compounds. Phases with the same sum of the atomic numbers of elements (Z), such as diamond and B_0.5 N_{0.5 (cub)} (Z = 6); pure silicon (Si) and Al_0.5 P_0.5 (Z=14); pure germanium (Ge) and Ga_0.5 As_0.5 (Z = 32)); pure grey tin (alpha-Sn) and In_0.5 Sb_0.5, and Cd_0.5 Te_0.5 (Z = 50) have the same heat capacity experimental values in the solid state. The proposed models can be used to both different binary and multicomponent phases. It helps to standardize the physicochemical constants.

Immune complexes (ICs) made of antibody-bound antigens exhibit immunomodulatory activities exploitable in a vaccination strategy to optimize vaccine efficacy. The modulatory effects of ICs are typically attributed to the Fc fragments of the antibody components, which engage Fc receptors, complement and complement receptors on various immune cells. These Fc-mediated functions facilitate the critical interplay between innate and adaptive immune systems to impact the quality and quantity of the elicited adaptive responses. In addition to the Fc contribution, the Fab fragment also plays an immunoregulation role. The antigen-binding domains of the Fab fragment can bind their specific epitopes at high affinity to sterically occlude these antigenic sites from recognition by other antibodies. Moreover, the Fab-mediated binding have been demonstrated to induce allosteric alterations at nearby or distant antigenic sites. In this review article, we survey published studies to illuminate how the immunomodulatory functions of ICs have been investigated or utilized in a vaccination strategy to fight against an array of infectious pathogens, culminating with IC vaccine designs aimed at preventing HIV-1 infection. In particular, we highlight IC vaccine candidates that exploit Fab-mediated steric and allosteric effects to direct antibody responses away or toward the V1V2 domain, the V3 loop, and other antigenic sites on the HIV-1 envelope gp120 glycoprotein. Like other HIV-1 vaccine approaches, the path for IC-based vaccines to reach the clinic faces major hurdles yet to be overcome; however, investigations into this vaccine strategy have provided insights into the multifaceted activities of antibodies beyond their conventional roles in the host defense against HIV-1 and other microbial pathogens.

Soil nitrogen (N) is a common limiting factor where soil N cycling is a key component of agro-ecosystems. Soil N transformation processes are largely mediated by microbes and understanding bacteria involvement in soil N cycling in agricultural systems has both agronomic and environmental importance. This 2-yr field scale study examined the abundances and spatial distributions of total bacterial community (16s RNA), bacterial involved in nitrification (amoA), and de-nitrification (narG, nirK, and nosZ) and soil physicochemical properties of winter wheat (Triticum aestivum L.) – soybean (Glycene max L.) double cropping with 2-3 weeks of spring grazing (WGS) and without grazing (WS) and of tall fescue (Festuca arundinacea (L.) Schreb.) pasture (TF) managed to near natural conditions with similar grazing. The TF had a significantly higher abundance of 16S rRNA, amoA, narG, nirK, and nosZ genes than the WS and WGS, which had similar levels between themselves. Soil organic matter (OM) and soil pH had a stronger effect on the N-cycling bacteria gene abundance. All bacterial gene concentrations and soil pH showed non-random distribution patterns with 141-186 m range autocorrelation. These results indicate that biological N transformation processes are more important in natural agricultural systems and the abundance of N-cycling bacteria can be manipulated by field scale management strategies.

The Sarcoma Assessment Measure (SAM) was developed as a sarcoma-specific patient-reported outcome measure to be used in clinical practice. We have reported in detail how SAM has been developed in collaboration with patients and healthcare professionals. The aim of this paper is to report the preliminary validation of SAM. The 22-item SAM was administered alongside a validated quality of life questionnaire and measure of activities of daily living. Linear modelling was used to build a measure, which had predictive validity in comparison to more established outcome measures. Of the 762 patients who participated in the study, 44.1% identified as male, and participant age ranged from 13-82 years. Clinically, participants presented with a range of soft tissue (82.2%) and bone (21.8%) sarcomas. Our preliminary analysis indicates that SAM accounts for 35% of the Global quality of life scale and 18% of the TESS so psychometrically it overlaps with quality of life and activities of daily living, but also measures distinct concerns. This demonstrates that this measure picks up issues that are important to patients with sarcoma that are not reflected in other measures. We have established the preliminary validity of SAM and believe it has utility as a patient-reported outcome measure both as a research tool and for assessing the impact of symptoms and dysfunction related to sarcoma as part of clinical care. Further validation using a larger and more clinically diverse sample is now needed.

While Twitter has been touted to provide up-to-date information about hazard events, the reliability of tweets is still a concern. Our previous publication extracted relevant tweets containing information about the 2013 Colorado flood event and its impacts. Using the relevant tweets, this research further examined the reliability (accuracy and trueness) of the tweets by examining the text and image content and comparing them to other publicly available data sources. Both manual identification of text information and automated (Google Cloud Vision API) extraction of images were implemented to balance accurate information verification and efficient processing time. The results showed that both the text and images contained useful information about damaged/flooded roads/street networks. This information will help emergency response coordination efforts and informed allocation of resources when enough tweets contain geocoordinates or locations/venue names. This research will help identify reliable crowdsourced risk information to enable near-real time emergency response through better use of crowdsourced risk communication platforms.

Sleep is an essential component of a healthy lifespan, influencing both physical and mental well-being along with good quality of life. Adequate sleep quality and quantity are associated with a host of health advantages, including enhanced immune function, learning and memory, emotional well-being, and cardiovascular health. Chronic sleep deprivation, or poor sleep quality, is associated with a variety of negative health outcomes, including an increased risk of obesity, diabetes, hypertension, depression, cancer, and even premature death. One compelling argument in favor of sleep as a predictor of a healthy lifespan is its effect on cellular repair and regeneration. During sleep, the body goes through important activities such as tissue repair, muscular growth, and memory consolidation. Sleep also helps the brain eliminate toxins and metabolic waste, which contributes to its optimal functioning. Without adequate sleep, these important processes are jeopardized, resulting in accelerated aging and greater susceptibility to chronic illnesses. Furthermore, sleep is essential for maintaining hormone balance, particularly those involved in appetite regulation and metabolism. Sleep disturbances can disrupt the regulation of these hormones, resulting in weight gain, metabolic diseases, and, ultimately, a shorter life span. Finally, prioritizing optimal sleep is pivotal for increasing longevity and general health. Emphasizing the importance of sleep hygiene and treating sleep-related dysfunctions should be part of the modern approach to extending healthy life.

Trees provide key ecosystem services, but the health and sustainability of these plants is under increasing biotic and abiotic threat, including from the growing incidences of non-native invasive plant pests (including pathogens). The island of Ireland (Ireland and Northern Ireland) is generally accepted to have a high plant health status, in part due to its island status and because of the national and international regulations aimed at protecting plant health. To establish a baseline of the current pest threats to tree health for the island of Ireland, the literature and unpublished sources were reviewed to produce a dataset of pests of trees on the island of Ireland. The dataset contains 396 records of pests of trees on the island of Ireland, the majority of pests being arthropods and fungi, and indicating potentially more than 44 non-native pest introductions. The reliability of many (378) of the records was judged to be high, therefore the dataset provides a robust assessment of the state of pests of trees recorded on the island of Ireland. We analyse this dataset and review the history of plant pest invasions, including (i) discussion on notable native and non-native pests of trees, (ii) pest interceptions at borders and (iii) pests and climate change. The dataset establishes an important baseline for the knowledge of plant pests on the island of Ireland, and will be a valuable resource for future plant health research and policy making.

In response to the National Institutes of Health (NIH) All of Us Medicine Research Initiative, the Precision Medicine Research (PreMeR) Diversity Consortium was formed by four institutions from the Research Centers in Minority Institutions (RCMI) Translational Research Network (RTRN). This synergistic approach proposed evidence-based, best practices used by experienced researchers to engage, recruit and retain diverse populations in the All of Us initiative. Conceptualization of the proposed approach was aided by social influence theories to better understand how people’s beliefs and opinions should be modified to affect change leading to action [1]. The Social-Ecological Model (SEM), for Health Promotion [2], from Stokols [1] and Community-Based Participatory (CBPR) Models[3],[4] guided proposed engagement, recruitment, and retention strategies contextualized with the individual, interpersonal, organizational, community, and policy spheres of influence. The PreMeR produced a partnership to evaluate and improve the effectiveness of current engagement, recruitment, and retention strategies for minority participation in scientific studies. This approach illustrates the need to incorporate multiple methods of engagement to reach a diverse audience to participate in scientific research. Engagement, recruitment, and retention strategies in community and biomedical research must be viewed as community engaged public health interventions, utilizing the same theoretical principles and approaches.

The development and qualification of CrAlN coatings deposited by DC magnetron sputtering offer new industrial solutions to increase the lifecycle of material forming tools (machining and shaping). This study focuses on the selection and optimization of deposition modes for CrAlN layers to be deposited on a 90CrMoV8 tool steel substrate. The adopted methodology aims to optimize the deposition conditions to meet the customer's requirement of a CrAlN coating thickness of approximately 2-3 µm for use in a hot forming process. Different polarizations using two Al and Cr targets, with both stationary and rotating substrate modes during deposition, were tested and evaluated. Characterizations of the CrAlN coating layers (microhardness, residual stress, structures) and performance in service (wear, friction, adhesion, corrosion) were chosen as selection criteria for a particular coating mode. The aluminum content plays a crucial role in the tribological and mechanical behavior of CrAlN layers. Corrosion resistance is more sensitive to the aluminum content for the stationary deposition mode. As a result, the rotating mode provides higher adhesion (+100%) and less wear (-60%) compared to the stationary mode. Therefore, depending on the likely performance in service, either a stationary or rotating mode could be applied for coating the functional surfaces of hot forming tools.

Isotopic stable analysis (SIA) is a powerful tool in the assessment of different types of ecological and physiological studies. For that, different preservative methods for the samples are commonly used prior to isotopic analysis. The effects of various preservative methods (drying, freezing, ethanol and formaldehyde) have been analyzed for C:N ratio, δ13C and δ15N on a variety of tissues including dorsal fins (three seahorse and two pipefish species), seahorse newborns (three seahorses species), and prey (copepods and different stages of Artemia) commonly used to feed the fishes in rearing conditions. The aims of the study were to: (i) evaluate isotopic effects of preservation methods across tissues; and (ii) construct the first conversion models available in syngnathid fishes. The preservation in ethanol and to a lesser extend in formaldehyde significantly affected δ13C values, whereas δ15N signatures were not affected significantly. Due to their low lipid content, the isotopic signals in fish fins were almost unaffected, supporting the suitability of dorsal fins as a convenient tool in isotopic studies on vulnerable species such as syngnathids. The regression equations provided permit the successful conversion of δ13C and δ15N values between preservative treatments. The conversion models can be applied to isotopic studies in the field and in the laboratory.

Polyamide 11 (PA11) is a plant-based nylon made from castor beans. Powder bed fusion laser sintering (PBF-LS) is an additive manufacturing process used for PA11 which allows the reuse of the unsintered powder. The unsintered powder is mixed with virgin powders at different refresh rates which has been studied extensively for most semi-crystalline polyamides. However, there is lack of information on the effect of using 100% reused PA11 powder and the number of times it is reused on its own during powder bed fusion laser sintering. This paper investigates the effect of reusing PA11 powder in PBF-LS and number of times it is reused on the dimensional accuracy, density, thermal and tensile properties. From 100% virgin powder to 3rd use of the powder, there is a decrease in powder wastage, decrease in crystallinity and tensile strength. These was associated with the polymerisation and cross-linking process of polymer chains, upon exposure to high temperature. This results in a higher molecular weight and hence density. From the 4th use to 10th reuse, the opposite was observed which was associated to an increase in high-viscosity and un-molten particles which resulted in defects in the PBF-LS parts.

Cosmopolitan Gram-negative cyanobacteria may affect human and animal health by contaminating terrestrial, marine and freshwater environments with toxins, such as lipopolysaccharide (LPS). The cyanobacterial genus Scytonema (S) produces several toxins, but to our knowledge the bioactivity of genus Scytonema LPS has not been investigated. We recently reported that cyanobacterium Oscillatoria sp. LPS elicited classical and alternative activation of rat microglia in vitro [1]. Thus, we hypothesized that treatment of brain microglia in vitro with either cyanobacteria S. javanicum or S. ocellatum LPS might stimulate classical and alternative activation with concomitant release of superoxide anion (O₂⁻), matrix metalloproteinase-9 (MMP-9) and cytokines and chemokines. Microglia were isolated from neonatal rats and treated in vitro with either S. javanicum LPS, S. ocellatum LPS, or E. coli LPS (positive control) in a concentration-dependent manner for 18 hours at 35.9 °C. We observed that treatment of microglia with either E. coli LPS, S. javanicum or S. ocellatum LPS generated statistically significant and concentration-dependent O₂⁻, MMP-9 and pro-inflammatory cytokines IL-6 and TNF-α, pro-inflammatory chemokines MIP-2/CXCL-2, CINC-1/CXCL-1 and MIP-1α/CCL3, and the anti-inflammatory cytokine IL-10. Thus, our results provide experimental support for our working hypothesis because both S. javanicum and S. ocellatum LPS elicited classical and alternative activation of microglia and concomitant release of O₂^-, MMP-9 and cytokines and chemokines in a concentration-dependent manner. To our knowledge this is the first report on the toxicity of cyanobacteria S. javanicum and S. ocellatum LPS to microglia, an immune cell type involved in neuroinflammation and neurotoxicity in the central nervous system.

Introduction Acalypha indica (AI) is an Ayurvedic medicinal plant. Some of this plant’s phytochemicals have been reported to cause oxidative stress in red blood cells. However, we know very little about those chemicals due to a dearth of literature. We present a case in which a patient with a previously unidentified glucose-6-phosphate dehydrogenase (G6PD) deficiency experienced acute hemolysis after ingesting fresh AI plant leaves. Case Presentation A 65-year-old man presented with jaundice, pallor, and haematuria following ingestion of the "Kuppamenia mallum" dish. His peripheral blood picture showed bite cells and Heinz bodies. A positive Brewer's test raised the clinical suspicion of G6PD deficiency. Low values of the G6PD level assessment at the follow-up visit confirmed the diagnosis. Conclusion Although AI is regarded as a medicinal plant, acute hemolysis can also occur after consumption in G6PD-deficient patients. This case emphasises the need for further research to identify the phytochemicals and their concentrations that can induce toxicity.

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

Background & Aims: Globally, liver diseases account for 2 million deaths per year. For those with advanced liver disease the only curative approach is liver transplantation. However, less than 10% of those in need get a liver transplant due to limited organ availability. To circumvent this challenge, there has been a great focus in generating a bioengineered liver. Despite its essential role in liver functions, a functional biliary system has not yet been developed. In this framework, exploration of epithelial cell self-organogenesis and microengineering-driven geometrical cell confinement allow to envision the bioengineering of a functional biomimetic intrahepatic biliary tract. Approach: Three-dimensional (3D) bile ducts were built in vitro by restricting cell adhesion to two-dimensional (2D) patterns to guide cell self-organization. Tree shapes mimicking the configuration of the human biliary system were micropatterned on glass slides, restricting cell attachment to these areas. Different tree geometries and culture conditions were explored to stimulate self-organogenesis of normal rat cholangiocytes (NRCs) used as a biliary cell model, either alone or in coculture with human umbilical endothelial cells (HUVECs). Results: Pre-seeding the micropatterns with HUVECs promoted luminogenesis with higher efficiency to yield functional branched biliary tubes. Lumen formation, apico-basal polarity, and preservation of the cholangiocyte phenotype were confirmed. Moreover, intact and functional biliary structures were detached from the micropatterns for further manipulation. Conclusion: This study presents physiologically relevant 3D biliary duct networks built in vitro from 2D micropatterns. This opens opportunities for investigating bile duct organogenesis, physiopathology, and drug testing.

The provenance of the aminoacyl-tRNA synthetases (aaRS) poses challenging questions because of their role in the emergence and evolution of genetic coding. We investigate evidence about their ancestry from curated structure-based multiple sequence alignments of a structurally invariant “scaffold” shared by all 10 canonical Class I aaRS. Three uncorrelated phylogenetic metrics—residue-by-residue conservation, its variance, and row-by-row cladistic congruence—imply that the Class I scaffold is a mosaic assembled from distinct, successive genetic sources. These data are especially significant in light of: (i) experimental fragmentations of the Class I scaffold into three partitions that retain catalytic activities in proportion to their length; and (ii) evidence that two of these partitions arose from an ancestral Class I aaRS gene encoding a Class II ancestor in frame on the opposite strand. Phylogenetic metrics of different modules vary in accordance with their presumed functionality. A 46-residue Class I “protozyme” roots the Class I molecular tree prior to the adaptive radiation of the Rossmann dinucleotide binding fold that refined substrate discrimination. Such rooting is consistent with near simultaneous emergence of genetic coding and the origin of the proteome, resolving a conundrum posed by previous inferences that Class I aaRS evolved long after the genetic code had been implemented in an RNA world. Further, pinpointing discontinuous enhancements of aaRS fidelity establishes a timeline for the growth of coding from a binary amino acid alphabet.

More than 179,000 individuals have fallen ill of the Coronavirus disease (COVID-19) caused by the SARS-CoV-2 virus, which first emerged in China less than four months ago in December 2019. As of today, there exist no approved treatments against COVID-19. Vaccines are being developed, but they will take time, at least one year, to reach the population. Drug repositioning represents a fast track because already approved medicines have been broadly tested through multiple trials. We developed a repositioning strategy that mostly leads to candidates that are commonly used. The advantages are that they will facilitate proof of concept in humans through a “real-world evidence” approach and should be rapidly available to the population. We focus on the established research results that the unfolded protein response (UPR) and autophagy pathways of the host cells are essential to the life cycle of previously known coronaviruses. We performed the relevant bioinformatics analysis to understand and confirm if SARS-CoV-2 may interact with these druggable pathways. Based on these considerations, we prioritized two additional druggable pathways, which are important to the viral life cycle and tightly connected to UPR/autophagy signaling: the mitochondrial permeability transition pores (MPTP) and NLRP-3 inflammasome pathways. These four important pathways are perturbed in most major common diseases and have therefore been targeted by numerous broadly prescribed drugs. We have identified 97 approved drugs that are known to modulate these four identified pathways, and which represent, therefore, interesting repositioning candidates. Although it is indisputable that these drugs should never be used for immediate self-medication against COVID-19, we notice that some of them could also be prescribed to individuals who have COVID-19 comorbidities (e.g., hypertension). It is debated if these comorbidities are linked to the pathology itself (e.g., hypertension) or the drugs used to treat the pathology (e.g., sartans). Therefore, relevant preclinical tests and massive electronic health records (i.e., real-world evidence) must be used to pre-screen them and check the COVID-19 prognosis of individuals taking these drugs.

Vision impairment may delay responses to hazards when driving. In a proof-of-concept driving simulator study, we evaluated a hazard warning device designed for vision impaired drivers. Three groups participated: 11 persons with central vision loss (CVL; median age 60 years), 12 with homonymous field loss (HFL; 52 years) and 11 with normal vision (NV; 60 years). CVL is characterised by impaired visual acuity and contrast sensitivity while HFL is a loss of vision in the same half of the visual field (blind side) in both eyes. Participants completed drives with and without the device which gave a directional vibro-tactile warning for an approaching pedestrian hazard when collision risk exceeded a pre-defined threshold. Warnings significantly (p< 0.001) reduced brake response times for CVL (∆= 0.54s) and HFL (∆= 0.30s), but not NV participants. For HFL participants, the reduction was greater (p = 0.02) for hazards on the blind (∆= 0.57s) than seeing side (∆= 0.10s). The warnings significantly reduced collision rates for CVL participants from 11 to 0% (all hazards) and for HFL participants from 30 to 1.7% (blind side hazards). Thus, hazard warnings may be beneficial in improving safety of vision impaired drivers; further research is warranted.

Sex differences are essential factors in disease etiology and manifestation in many diseases such as cardiovascular disease, cancer, and neurodegeneration (1). The biological influence of sex differences (including genomic, epigenetic, hormonal, immunological, and metabolic differences between males and females) and the lack of biomedical studies considering sex differences in their study design has led to several policies. For example, the National Institute of Health’s (NIH) sex as a biological variable (SABV) and Sex and Gender Equity in Research (SAGER)) policies to motivate researchers to consider sex differences (2). However, drug repurposing, a promising alternative to traditional drug discovery by identifying novel uses for FDA-approved drugs, lacks sex-aware methods that can improve the identification of drugs that have sex-specific responses (1,3–5). Sex-aware drug repurposing methods either select drug candidates that are more efficacious in one sex or deprioritize drug candidates based on if they are predicted to cause a sex-bias adverse event (SBAE), unintended therapeutic effects that are more likely to occur in one sex. Computational drug repurposing methods are encouraging approaches to develop for sex-aware drug repurposing because they can prioritize sex-specific drug candidates or SBAEs at lower cost and time than traditional drug discovery. Sex-aware methods currently exist for clinical, genomic, and transcriptomic information (3,6,7). They have not expanded to other data types, such as DNA variation, which has been beneficial in other drug repurposing methods that do not consider sex (8). Additionally, some sex-aware methods suffer from poorer performance because a disproportionate number of male and female samples are available to train computational methods (3). However, there is development potential for several different categories (i.e., data mining, ligand binding predictions, molecular associations, and networks). Low-dimensional representations of molecular association and network approaches are also especially promising candidates for future sex-aware drug repurposing methodologies because they reduce the multiple hypothesis testing burden and capture sex-specific variation better than the other methods (9,10). Here we review how sex influences drug response, the current state of drug repurposing including with respect to sex-bias drug response, and how model organism study design choices influence drug repurposing validation.

In air-breathing proton exchange membrane fuel cells (Air PEM FCs), high rate of water evaporation from the cathode might influence the resistance of the membrane electrode assembly (MEA), which is highly dependent on the water content of the Nafion membrane. We propose a dead-end hydrogen anode as a means of intermediate storage of water/humidity for self-humidification of the membrane. Such inflatable bag integrated with the PEM FC has a potential in blimp applications for anode self-humidification. A dynamic numerical water balance model, validated by experimental measurements, is derived to predict the effect of MEA configuration, membrane’s hydration state, and water transfer rate at the anode on MEA resistance and performance. The experimental setup included humidity measurements, polarization and electrochemical impedance spectroscopy tests to quantify the effect of membrane hydration on its resistance in a lightweight MEA integrated with an inflatable dead-end hydrogen storage bag. Varying current density (20 mA, 40 mA and 60 mA) and cathode humidity (20, 50 and 80%) were examined and compared with the numerical results. The validated model predicts that the hydration state of the membrane and water transfer rate at the anode can be increased by using a thin membrane and thicker gas diffusion layer.

We presents results obtained from the numerical simulation of the gas-phase chemical kinetics in atmospheric pressure air non-equilibrium plasmas. In particular we have addressed the effect of pulsed operation mode of a planar dielectric barrier discharge. As it was conjectured, the large difference in the time scales involved in the fast dissociation of molecules in plasmas and their subsequent reactions to produce stable chemical species, makes the presence of a continuously repeated plasma production stage unnecessary and a waste of electrical power and efficiency. Results on NOx remediation, ozone production, water vapor and ammonia dissociation are discussed. A few comparisons with experimental findings in a dielectric barrier discharge reactor already used for applications is briefly addressed too. Our results clearly indicate a pattern for the optimization of the discharge using a carefully designed repetition rate and duty-cycle.

Pandemics, and other risk-related contexts, require dynamic changes in behavior as situations develop. Human behavior is influenced by both explicit (cognitive) and implicit (intuitive) factors. In this study, we used psychological distance as a lens to understand what influences our decision-making with regards to risk in the context of COVID-19. The study was based on the rationale that our relational needs are more concrete to us than the risk of the virus. First, we explored the impact of social-psychological distance on participants’ risk perceptions and behavioral willingness. As hypothesized, we found that close social relationships of agents promoted willingness to engage in risky behavior. In the second phase, we tested an intervention designed to increase the concreteness of information about virus transmission as a mechanism to mitigate the bias of social influence. We found that the concreteness intervention resulted in significantly reduced willingness to engage in risky behavior. As such, communications aimed at changing the behavior of citizens during times of increased risk or danger, should consider conceptually concrete messaging when communicating complex risk, and hence may provide a valuable tool in promoting health-related behavior.

Epilepsy is one of the most common disorders of the central nervous system, impacting nearly 50 million people around the world. Heterogeneous in nature, epilepsy presents in children and adults alike. Currently, surgery is the only treatment that can cure epilepsy. However, not all individuals are eligible or have successful outcomes. Difficulty in accessing samples of human brain tissue along with advances in sequencing technology have driven researchers to investigate sampling liquid biopsies in blood, serum, plasma, and cerebrospinal fluid within the context of epilepsy. Liquid biopsies provide minimal or non-invasive sample collection approaches and can be assayed relatively easily across multiple time points, unlike tissue-based sampling. Various efforts have investigated circulating nucleic acids from these samples including microRNAs, cell-free DNA, transfer RNAs, and long non-coding RNAs. Here, we review nucleic acid-based liquid biopsies in epilepsy to improve understanding of etiology, diagnosis, prediction, and therapeutic monitoring.

Chronic granulomatous disease (CGD) is a primary immunodeficiency caused by a defect in the phagocytic function of the innate immune system owing to mutations in genes encoding the five subunits of the nicotinamide adenine dinucleotide (NADPH) oxidase enzyme complex. This review aimed to provide a comprehensive approach to the pathogens associated with chronic granulomatous disease (CGD) and its management. The topics covered included common pathogens infecting CGD patients, granulomas, and CGD-related infectious diseases, including invasive aspergillosis, Mulch pneumonitis, and liver abscesses. In addition, we also covered the differential diagnosis of CGD and its management. Patients with CGD, often children, have recurrent life-threatening infections and may develop infectious or inflammatory complications. The most common microorganisms observed in the patients with CGD are Staphylococcus aureus, Aspergillus spp, Candida spp, Nocardia spp, Burkholderia spp, Serratia spp, and Salmonella spp. Triple-dose antimicrobial prophylaxis with empiric regimens is recommended. Therefore, therapeutics against this disease must be optimised, considering the lack of curative therapies and the long-term side effects of prophylactic regimens. Consequently, allogeneic haematopoietic stem cell transplantation from a human leukocyte antigen-identical donor has been proven to cure CGD.

Alzheimer’s disease is the most common neurodegenerative disease and affects persons of all races, ethnic groups, and sexes. The disease is characterized by neuronal loss leading to cognitive decline and memory loss. There is no cure and the effectiveness of existing treatments is limited and depends on the time of diagnosis. The long prodromal period, during which patients’ ability to live a normal life is not affected despite neuronal loss, often leads to a delayed diagnosis because it can be mistaken for normal aging of the brain. In order to make a substantial impact on AD patients, early diagnosis may provide a greater therapeutic window for future therapies to slow AD-associated neurodegeneration. Current gold standards for disease detection include magnetic resonance imaging and positron emission tomography scans, which visualize amyloid β and phosphorylated tau depositions and aggregates. Liquid biopsies, already an active field of research in precision oncology, are hypothesized to provide early disease detection through minimally or non-invasive sample collection techniques. Liquid biopsies in Alzheimer’s disease have been studied in cerebrospinal fluid, blood, ocular, oral, and olfactory fluids. However, most of the focus has been on blood and cerebrospinal fluid due to biomarker specificity and sensitivity attributed to the effects of the blood-brain barrier and inter-laboratory variation during sample collection. Many studies have identified amyloid β and phosphorylated tau levels as putative biomarkers, however, advances in next-generation sequencing-based liquid biopsy methods have led to significant interest in identifying nucleic acids species associated with Alzheimer’s disease from liquid tissues. Differences in cell-free RNAs and DNAs have been described as potential biomarkers for AD and hold the potential to affect disease diagnosis, treatment, and future research avenues.

Revolutionizing Lng Plant Construction and its Comprehensive Comparative Analysis And Evaluation Of Modular Design Development Versus Stick-Built Approach For Enhanced Efficiency And Cost-Effectiveness,.Although the utilization of modularization concepts in the LNG industry remains limited, this study focuses on exploring their potential. It is worth noting that modular units typically incur higher costs compared to field erected units due to the additional requirements of structural steel and robustness for transportation purposes.Nevertheless, the increased cost of modularization can often be balanced by conducting the work at the fabrication site instead of on-field construction. This approach reduces the overall project cost by minimizing field construction expenses and shortening the construction schedule. The objective of this paper is to assess and compare LNG modularization options for a newly established LNG facility in comparison to a conventional stick-built plant used as the base case.:The paper delves into various topics related to LNG plant construction, such as the development of modular units, a comprehensive comparison of different options, evaluation of construction schedules and manpower requirements, logistics considerations, and a recommended approach for design and construction. The cost estimates and engineering, procurement, and construction (EPC) schedules are meticulously compared for each option. Additionally, an inshore/near shore gravity base structure (GBS) option is included for further comparison. It is crucial to emphasize that establishing general costs is not possible as each project is distinct and requires individual study and analysis.:Each project has unique characteristics, resulting in varying shapes of cost curves and break-even points. The outcomes of the feasibility evaluation play a crucial role in determining the extent to which the modular approach to construction is advantageous for the specific project at hand. The evaluation takes into consideration multiple factors to determine the potential benefits of adopting a modular construction approach, allowing decision-makers to make informed choices regarding the project's construction methodology

Psychological readiness following Anterior Cruciate ligament Reconstruction (ACLR) correlates with different return to sport outcomes. However, the relationship between strength and power and psychological readiness remains unexplored. The aim of this study was to investigate the relationship between the Anterior Cruciate Ligament Return to Sport After Injury (ACL-RSI) scores and various hamstrings and quadriceps strength and power variables. Twelve participants (20.7±2.5 years old; 174.2±7.5 cm; 70.2±8.5 kg; 18.2±8.3% of body fat) who had an ACLR nine months or more before the study completed the ACL-RSI questionnaire and isokinetic strength testing of the hamstrings and quadriceps (60°.s-1 and 180°.s-1). Based on ACL-RSI scores, they were divided into “cases” and “controls”, deemed not psychologically ready and psychologically ready to return to previous sport performance (PILOS), respectively. The main findings are that quadriceps’ and hamstrings’ rate of torque development (RTD) and time since surgery were determinants of psychological readiness following ACLR. Furthermore, compared to controls cases showed significantly lower angle-specific quadriceps and hamstrings torque close to extension and lower RTD, but no difference in peak torque. These results suggest that physiotherapists should facilitate athletes’ RTS by focusing on the restoration of RTD and strength at angles close to full knee extension.

Lung cancer represents the most common form of cancer accounting for 1.8 million deaths globally in 2020.The 5-year relative survival rate for lung cancer is lower than many other leading cancer types. Over the last decade the treatment for advanced and metastatic non small cell lung cancer have dramatically improved due to the development of immune checkpoint inhibitors and the identification of targetable driver mutations. Recently, potentially effective inhibitors of a hitherto untargetable oncogenic driver mutation in NSCLC, Kirsten Rat Sarcoma (KRAS) have been developed. KRAS mutations are found in 20-25% of NSCLC and represent the most frequent mutation. The mutation is almost exclusively detected in adenocarcinoma and is found among smokers 90% of the time. Along with the development of new drugs that have been showing promising activity, resistance mechanisms have begun to be clarified. The aim of this review is to unwrap the biology of KRAS in NSCLC with a specific focus on primary and secondary resistance mechanisms and their possible clinical implications.

The current COVID-19 pandemic is one of the most devastating events in recent history. The virus causes relatively minor damage to young, healthy populations, imposing life-threatening danger to the elderly and people with diseases of chronic inflammation. Therefore, if we could reduce the risk for vulnerable populations, it would make the COVID-19 pandemic more similar to other typical outbreaks. Children don’t suffer from COVID-19 as much as their grandparents and have a much higher melatonin level. Bats are nocturnal animals possessing high levels of melatonin, which may contribute to their high anti-viral resistance. Viruses induce an explosion of inflammatory cytokines and reactive oxygen species, and melatonin is the best natural antioxidant that is lost with age. The programmed cell death coronaviruses cause, which can result in significant lung damage, is also inhibited by melatonin. Coronavirus causes inflammation in the lungs which requires inflammasome activity. Melatonin blocks these inflammasomes. General immunity is impaired by anxiety and sleep deprivation. Melatonin improves sleep habits, reduces anxiety and stimulates immunity. Fibrosis may be the most dangerous complication after COVID-19. Melatonin is known to prevent fibrosis. Mechanical ventilation may be necessary but yet imposes risks due to oxidative stress, which can be reduced by melatonin. Thus, by using the safe over-the-counter drug melatonin, we may be immediately able to prevent the development of severe disease symptoms in coronavirus patients, reduce the severity of their symptoms, and/or reduce the immuno-pathology of coronavirus infection on patients’ health after the active phase of the infection is over.

Expressions for the axial pressure profiles in a cylindrical channel and between parallel plates or a rectangular channel with large aspect ratio, with Maxwell slip gas flow are derived from first principles. The resulting expressions, which only involve the inlet and outlet pressures and the channel dimensions, will be useful in modelling or simulations of channel flows at Knudsen numbers in the range 0.001–0.1, such as in MEMS and NEMS. The expression for a cylindrical channel is validated by deriving from it an expression for the channel mass flow, which is shown to agree with a known expression for the mass flow through cylindrical channels with Maxwell slip flow. The expression for flow between parallel plates is found to agree with the zeroth order relation derived by Arkilic et al. using perturbation analysis. The effect of the accommodation coefficient on the pressure profile in a cylindrical channel is shown.

There is growing interest in the application of fecal microbiota transplants (FMTs) in small animal medicine, but there are few published studies that have tested their effectiveness in the domestic cat (Felis catus). Here we use 16S rRNA gene sequencing to examine fecal microbiome changes in 68 domestic cats with chronic digestive issues that underwent FMT treatment using lyophilized stool that was delivered in oral capsules. Fecal samples were collected from FMT recipients before and two weeks after treatment, as well as from their stool donors, and healthy animals. We found that according to their owners, 77% of cats were reported to show improvement in their clinical signs (termed ‘Responders’), and 23% were reported to exhibit no change or a worsening of their clinical signs (termed ‘Non-Responders’). Variation in the fecal microbiomes of FMT recipients most strongly correlated with host clinical signs, diet, and IBD diagnosis. The relative abundances of Collinsella, Negativibacillus, Parabacteroides, and Peptoclostridium changed differentially in FMT recipients. Overall, on average 13% of the bacterial amplicon sequence variants (ASVs) were shared between stool donors and FMT recipients (excluding ASVs already present in FMT recipients prior to treatment). The most commonly shared ASVs were classified as Prevotella 9, Peptoclostridium, Bacteroides, Collinsella and unclassified Lachnospiraceae. Lastly, FMT recipients that had recently taken antibiotics exhibited increases in microbiome similarity to an age-matched healthy reference set compared to other cats. Cats that had diarrhea or diarrhea with vomiting became more similar to healthy cats than did cats exhibiting other clinical signs. Overall, our results suggest that oral capsule FMT treatment was effective in this group of cats and microbiome responses may be modulated by the FMT recipient’s initial presenting clinical signs, prior IBD diagnosis, recent antibiotic use, and their diet.

Background: Crohn’s and Ulcerative Colitis Questionnaire-32 (CUCQ-32) is a validated questionnaire to measure the quality of life (QoL) in inflammatory bowel disease (IBD). However, it does not have stoma specific questions and can be lengthy. This study aimed to validate a subset of the CUCQ-32 that would be suitable for patients with a stoma. Methods: Baseline data were collected from a cohort of patients with acute ulcerative colitis who were participating in the CONSTRUCT multi-centre clinical trial. A subset of the CUCQ-32 questions was selected by stepwise regression. Further validation was examined using data from the UK IBD biological therapies audit. Construct validity was carried out using the EuroQol 5 dimensions (EQ5D) questionnaire, Simple Clinical Colitis Activity Index (SCCAI) and the Harvey-Bradshaw Index (HBI). Literature review and an expert focus group identified supplementary questions to cover patients with a stoma. Test-retest analysis was done during the patients’ second follow up visits. Results: Using the data from 124 patients, a short version questionnaire (CUCQ-12) was developed. Further validation using data from 484 patients with IBD as part of the UK IBD biological therapies audit. Using the data from 61 patients with a stoma, we identified 5 stoma specific questions for the CUCQ-12+. The CUCQ-12+ demonstrated excellent internal consistency (Cronbach’s α= 0.86); established effective reproducibility (intra-class correlation coefficient= 0.74); correlated well with the EQ5D (r= - 0.48), HBI (r= 0.45) and SCCAI (r= 0.43); and represented good responsiveness statistics (>0.5). Conclusions: CUCQ-12+ is a valid and reliable QoL measure that can be used for all patients with IBD in clinical practice including patients with a stoma.

Recently, the Internet of Things (IoT) has attracted wide attention from many fields, especially healthcare, because of its large capacities of information perception and collection. In this paper, we present an IoT-based home telehealth system for providing smart healthcare management for individuals, especially older people. Each client node of the system is mainly composed of an electronic water meter that records the user's daily water usage and an unobtrusive sleep sensor that monitors the user's physiological parameters during sleep such as heart rate (HR), respiratory rate (RR), body movement (BM), and states on the bed or outside the bed. The sleep sensor senses the biosignals and states by a sensor matrix composed of 12 piezoelectric sensors. The collected data can be transmitted to a remote centralized cloud service by a wireless home gateway for analyzing the living pattern and rhythm of users. Furthermore, the periodic feedback of results can be provided to users themselves as well as their family and health advisers. In the present study, data collections from a total of 18 older subjects were made for one year to evaluate the effectiveness of the proposed system. By analyzing living pattern and rhythm, preliminary results indicate the effectiveness of the telehealth system and suggest the potential of the system regarding improvement of quality of life (QoL) of older people and promotion of their health.

Cissus populnea Guill. & Perr. (Vitaceae) is used in traditional medicine to treat microbial infec-tions, venereal diseases, and infertility, among others. The aim of the research is to isolate and characterize the antimicrobial constituent(s) from the stem of C. populnea. The n-butanol fraction of C. populnea being most active was subjected to silica gel column chromatography which led to the isolation of a white solid and white crystalline substances coded compounds C1 and C4C5, respectively. Spectral analysis (1D & 2D-NMR) of the isolated compounds and comparison with literature data indicated C1 to be Bis-(2-ethyloctyl)-phthalate and C4C5 to be a mixture of stig-masterol and β-sitosterol; C4C5 exhibited zone of inhibition ranging from 24 – 29 mm against the test organisms with Candida albicans being the most sensitive organism while Trichophyton rubrum was the least sensitive organism. The standard drugs, Ciprofloxacin had 27 – 37 mm while Flu-conazole and Fulcin exhibited zone of inhibition ranging from 34 mm and 29 – 32 mm, respec-tively. The MIC and MBC/MFC values for C4C5 ranges from 12.5 – 25.0 µg/cm3 and 25.0 – 50.0 µg/cm3 against MRSA, S. aureus, E. coli, C. albicans, T. rubrum, and T. mentagrophyte, respectively. In conclusion, three bioactive compounds were identified for the first time from the stem of C. populnea

Large ruminant production is associated with high greenhouse gas emissions (GHGe) intensity, with the highest in southeast Asia being Laos at 102.9 CO2eq/kg meat produced, compared with average global meat emissions intensity of 33 CO2eq/kg. As recent studies in Laos identified emissions control molasses blocks (ECBs) achieved abatement of 470kg CO2eq/20kg block consumed, a study was conducted with a supplement mix with reported methane reducing properties, containing plant tannins and citral extract, salt, molasses and water. Groups of housed dairy buffalo (n=7) and pasture-fed grazing beef cows (n=11) were randomly selected, body condition scores estimated (BCS:1-5) and baseline nasa-oral methane eructation measured daily for 2 weeks. All animals were offered 300-400g/day of the mix for a month, with buffalo accessing abundant fresh cut forages whereas the grazing cows accessing rice straw and pasture declining in quality and quantity due to severe drought. The buffalo consumed all of the mix and retained their BCS of 3, whereas the cattle consumed between 200-300g/day of the mix and their BCS declined from 1.5 to 1.0 during the trial. Analysis of data points (buffalo n=309; cattle n=378) found average methane concentration (AMP) per animal of both cohorts increased over the 2 week baseline period, then declined during the supplementation period by 36% in the buffalo and 18% in cattle cohorts.

Supermarkets in Port Harcourt (PH) city, Nigeria, predominantly rely on diesel electricity generation due to grid instability, leading to high cost of electricity prices. Although solar photovoltaic (PV) systems have been proposed as an alternative, these supermarkets have yet to adopt them, mainly due to high investment costs and a lack of awareness of the long-term financial and environmental benefits. This paper examines the technical and economic practicality of a PV system for these supermarkets using the PVsyst software and a spreadsheet model. Solar resources showed that PH has a daily average solar radiation and temperature of 4.21 kWh/m2/day and 25.73℃, respectively. Market Square, the supermarket with the highest peak power demand of 59.8 kW, and a 561 kWh/day load profile, was chosen as a case study. A proposed PV system with a power capacity of 232 kW, battery storage capacity of 34,021 Ah, a charge controller size of 100 A/560V, and an inverter with a power rating of 60V/75 kW has been designed to meet the load demand. The economic analysis showed a $266,936 life cycle cost, $0.12 per kWh levelized cost of electricity (LCOE), 4-year simple payback time, and a 20.5% internal rate of return (IRR). The PV system is feasible due to its positive net present value (NPV) of $165,322 and carbon savings of 582 tCO2/year.

Cuffless sphygmomanometers may be useful alternative blood pressure monitors for screening and home healthcare. The main requirements for these devices are accuracy in the resting state, accuracy during dynamic blood pressure changes, and long-term stability. Intermittent measurements can ensure that the accuracy of active measurements mirrors that of measurements in the resting and dynamic states. This brief report proposes a new protocol to evaluate long-term stability based on a comparison with a medically approved cuff-based automated sphygmomanometer rather than an auscultatory sphygmomanometer. Dynamic changes in blood pressure are not usually assessed based on intermittent measurement with an over-the-counter (OTC) sphygmomanometer. Thus, validation testing focused on the accuracy of the OTC cuffless sphygmomanometer in the resting state and the long-term stability of the device, and the results were similar to those of the cuff-based sphygmomanometer. Further research and discussions are necessary to develop standards derived from high-quality evidence for manufacturers of OTC sphygmomanometers.