Background: The Davidson Airway Function & Nasal Evaluation (DAFNE) Scoring System was developed as an intuitive and research-based scoring system that could be validated through beta testing and easily introduced to healthcare providers of several subspecialties who treat nasal obstruction and breathing disorders (MDs, PAs, PTs, APRNs, DDSs, and DCs). This scoring system was shown to increase the knowledge of airway function, nasal measurement parameters, and identification of proper treatment options for sleep and breathing disorders. The basis for the DAFNE score was developed from a systematic review of nasal measurement data. Methods: Electronic searches of PubMed, MEDLINE, EMBASE Cochrane Library, and Scopus of publications between 1988-2022 were used to identify studies validating nasal function measurement parameters to create the algorithm for the DAFNE Score™. The systematic review was accomplished using the 2020 ‘Preferred Reporting Items for Systematic Reviews’ (PRISMA) guidelines. Results: Twenty studies met the inclusion criteria for systematic review. Primary outcomes measurements demonstrated reliability, repeatability and validity of the DAFNE measurement technologies, data and output. Conclusions: The data analysis and systematic review uncovered a need and framework to develop and validate a web-based software algorithm for global access to improve the understanding of data interpretation of nasal measurements from three nasal measurement technologies. DAFNE Scoring should be used as an adjunct tool in routine clinical practice and research to further understand the technology data output and how to collaborate with other healthcare providers to improve patient outcomes.

Abstract: Background: The diagnosis of nasal airway disorders relies on questionnaires, subjective data, and objective data. Interpretation of objective data obtained from measurement technology is not well understood by providers and researchers who use the equipment to test nasal airway function, justifying the need to cre-ate a new clinical tool. The Davidson Airway Function & Nasal Evaluation (DAFNE) Scoring System is a web-based scoring system that allows healthcare providers (MDs, PAs, PTs, APRNs, DMDs, DDSs, SLPs, and DCs) and researchers who treat nasal obstruction and breathing disorders to make more accurate diagnostic decisions, select the appropriate treatment for individualized patient care, monitor treatment progression and outcomes, and show how to approach a collaborative care model with other healthcare professionals. The current technologies, such as 4-phase rhinomanometry, use a simple approach that relies on a measurement tracing intersecting a color-coded y-axis on a four-quadrant graph with diagnostic numeric data output de-scribing nasal airflow and resistance. This is a good source of biofeedback demonstrating abnormal nasal breathing patterns but lacks interpretation guidelines to describe the severity of disease. The more sophisti-cated proprietary DAFNE approach uses multiple parameters which include airflow restriction, speed, vol-ume, and patient characteristics to identify patients’ disease progression much more accurately. Additionally, it explains how to segregate patients into appropriate treatment options which minimizes risks and compli-cations associated with sleep and breathing disorders while improving patient outcomes. Methods: Electronic searches of PubMed, MEDLINE, EMBASE Cochrane Library, and Scopus of publications between 1988-2022 were necessary to identify studies which determined the ranges of nasal function measurement parameters among three airway measurement technologies used in writing the DAFNE Score algorithm. The performance of DAFNE was evaluated compared to the research data and patient demographics used in previous studies. Results: By using primary outcome measurements from the literature, we were able to create a reliable, re-peatable, and validated tool to facilitate patient identification, treatment stratification, and collaboration for sleep and nasal breathing dysfunction. Subsequently, we found DAFNE could be used to identify the appro-priateness of a sleep study. Conclusions: DAFNE Scoring System has demonstrated the ability to detect high risk patients in the pediatric and adult populations susceptible of sleep apnea and breathing dysfunction needing a sleep study and treatment to improve nasal airway function and sleep. DAFNE Scoring System should be used as an adjunct tool in routine clinical practice and research to further understand the technol-ogy data output, identify patients at risk, stratify treatment options, progress, and stabilization after treatment, and how to collaborate with other healthcare providers to improve patient outcomes.

Seed bank survival underpins plant population persistence but studies on seed bank trait-environment interactions are few. Changes in environmental conditions relevant to seed banks occur in desert ecosystems owing to solar energy development. We developed a conceptual model of seed bank survival to complement methodologies using in-situ seed bank packets. Using this framework, we quantified the seed bank survival of two closely related annual desert plant species, one rare (Eriophyllum mohavense) and one common (Eriophyllum wallacei) and the seed bank-environment interactions of these two species in the Mojave Desert within a system that emulates microhabitat variation associated with solar energy development. We tracked 4,860 seeds buried across 540 seed packets and found, averaged across both species, that seed bank survival was 21% and 6% for the first and second growing seasons, respectively. After two growing seasons, the rare annual had a significantly greater seed bank survival (10%) than the common annual (2%). Seed bank survival, across both species, was significantly greater in Shade (10%) microhabitats compared to Runoff (5%) microhabitats and Control microhabitats (3%). Our study confers insight into this early life-stage across rare and common congeners and their environmental interactions using a novel conceptual framework for seed bank survival.

Computational Fluid Dynamics (CFD) simulations, based on Reynolds Averaged Navier Stokes (RANS) models, are a useful tool for a wide range of coastal and offshore applications, providing a high fidelity representation of the underlying hydrodynamic processes. Generating input waves in the CFD simulation is performed by a numerical wavemaker (NWM), with a variety of different NWM methods existing for this task. While NWMs, based on impulse source methods, have been widely applied for wave generation in depth averaged, shallow water models, they have not seen the same level of adoption in the more general RANS based CFD simulations, due to difficulties in relating the required impulse source function to the resulting free surface elevation for non-shallow water cases. This paper presents an implementation of an impulse source wavemaker, which is able to self-calibrate the impulse source function to produce a desired wave series in deep or shallow water at a specific point in time and space. Example applications are presented, for a numerical wave tank (NWT), based on the opensource CFD software OpenFOAM, for wave packets in deep and shallow water, highlighting the correct calibration of phase and amplitude. Also, the suitability for cases requiring very low reflection from NWT boundaries is demonstrated. Possible issues in the use of the method are discussed and guidance for good application is given.

The study describes the acute and delayed time course of recovery following the CrossFit® Benchmark Workout Karen. Eight trained men (28.4±6.4 years; 1RM back squat 139.1±26.0 kg) undertook the Karen protocol. The protocol consists of 150 Wall Balls, aiming to hit a target 3 meters high. Countermovement jump height (CMJ), creatine kinase (CK), and perceived recovery status scale (PRS) (general, lower and upper limbs) were assessed pre, post-0h, 24h, 48h and 72h after the session. The CK concentration 24h after was higher than pre-exercise (338.4 U/L vs. 143.3 U/L; effect size: 0.74; p≤0.05). At 48h and 72h following exercise, CK concentration had returned to baseline levels. The PRS general and of the lower limbs were lower in the 24-hours post-exercise compared to pre-exercise (PRS general: 4.7 ±1.5 and 7.9 ±1.7 mmol/L; and PRS of the lower limbs: 4.0 ±2.5 and 7.9 ±0.8, respectively). The PRS general, lower, and upper limbs were reduced at 48-post exercise compared to 72-hours post-exercise scores. Our findings provide insights into the fatigue profile and recovery in acute CrossFit® and can be useful to coaches effectively design the daily session.

There is compelling evidence that the nuclear receptor TRβ, a member of the thyroid hormone receptor (TR) family, is a tumor suppressor in thyroid, breast and other solid tumors. Cell-based and animal studies reveal that the liganded TRβ induces apoptosis, reduces an aggressive phenotype, decreases stem cell populations, and slows tumor growth through modulation of a complex interplay of transcriptional networks. TRβ-driven tumor suppressive transcriptomic signatures include repression of known drivers of proliferation such as PI3K/Akt pathway and activation of novel signaling (JAK1/STAT1) and metabolic reprogramming in both thyroid and breast cancers. The presence of TRβ is also correlated with a positive prognosis and response to therapeutics in BRCA+ and triple-negative breast cancers respectively. Ligand activation of TRβ enhances sensitivity to chemotherapeutics. TRβ co-regulators and bromodomain-containing chromatin remodeling proteins are emergent therapeutic targets. This review considers TRβ as a potential biomolecular diagnostic and therapeutic target.

Damaged connective tissues between the bone and tendons or ligaments are common among adults regardless of activity level. Achilles tendinosis is one of the most common tissue defects and enthesopathies. The patient in this study is a 54-year-old female with chronic Achilles tendinosis from chronic enthesopathy at the Achilles tendon insertion with a retrocalcaneal exostosis for three years who has failed standard-of-care practices for over two years. The patient received extracorporeal pulsed-activated therapy (EPAT) before applying 2ml of CryoText, a Wharton’s jelly tissue allograft. The patient then received class IV laser therapy treatments twice weekly for three weeks. The patient started with a 10/10 VAS at the initial visit. At five weeks post-application, the patient’s score had improved by 80% at 2/10 VAS. By week 13, the patient rated her pain as 0/10 VAS. The improvement in patient-reported pain and functionality reported in this study after the application of Wharton’s Jelly, EPAT, and class IV laser therapy warrants future research studying the safety and efficacy of these patient care modalities together.

Cu-ions dispersed on reduced graphene RGo prepared and characterized in a liquid state in ethanol. Either constant ultrasounds or a sequence of ultrasounds (15s working, 15s stop) were applied for 6 min or 2h overall time, at a power of 500 W. Commercial graphite in ethanol was introduced at a concentration of 0.04 g/mL and CuCl2 2.5 H2O concentrations between 0.012 and 0.04 g/mL were used. The structural characterizations performed by XRD, microscopic, and spectroscopic techniques, after a centrifugation at 5000 rpm applied 12 min before Cu-introduction, led to conclude that: 1) Without copper, negative peaks in UV spectra were detected with concentrated pure graphene solutions, indicating light emission as nicely confirmed next by fluorescence measurements, 2) After addition of copper chloride and equilibration for 2 min , very intense and narrow peaks of intensity larger than 10 were observed. These peaks due to collective excitations generating plasmons were suppressed at a higher dilution and also if the cell with one cm optical path was replaced by a narrower cell with a 0.2 cm path. When plasmons were suppressed, in the UV spectral range, a band gap due to the energy transition between the valence filled  orbitals and conducting empty * orbitals, was observed. The presence of Cu (II) and Cu (I) cations were evidenced by Visible NIR spectroscopy. The formed “green” liquors containing Cu (II) Cu (I) /graphene in ethanol were stable in air for months and had good photocatalytic visible properties as demonstrated by the decomposition of two dyes.

Polycystic ovary syndrome (PCOS) is increasingly being characterized as an evolutionary mismatch disorder that presents with a complex mixture of metabolic and endocrine symptoms. The Evolutionary Model proposes that PCOS arises from a collection of inherited polymorphisms that have been consistently demonstrated in a variety of ethnic groups and races. In-utero developmental programming of susceptible genomic variants are thought to predispose the offspring to develop PCOS. Postnatal exposure to lifestyle and environmental risk factors results in epigenetic activation of developmentally programmed genes and disturbance of the hallmarks of health. The resulting pathophysiological changes represent the consequences of poor-quality diet, sedentary behaviour, endocrine disrupting chemicals, stress, circadian disruption, and other lifestyle factors. Emerging evidence suggests that lifestyle-induced gastrointestinal dysbiosis plays a central role in the pathogenesis of PCOS. Lifestyle and environmental exposures initiate changes that result in disturbance of the gastrointestinal microbiome (dysbiosis), immune dysregulation (chronic inflammation), altered metabolism (insulin resistance), endocrine and reproductive imbalance (hyperandrogenism), and central nervous system dysfunction (neuroendocrine, autonomic nervous system). PCOS can be a progressive metabolic condition that leads to obesity, gestational diabetes, type 2 diabetes, metabolic-associated fatty liver disease, metabolic syndrome, cardiovascular disease, and cancer. This review explores the mechanisms that underpin the evolutionary mismatch between ancient survival pathways and contemporary lifestyle factors involved in the pathogenesis and pathophysiology of PCOS.

The virtually complete loss of intestinal worms, known as helminths, from Western society has resulted in elimination of a range of helminth-induced morbidities. Unfortunately, that loss has also led to inflammation-associated deficiencies in immune function, ultimately contributing to widespread pandemics of allergies, autoimmunity, and neuropsychiatric disorders. Several socio-medical studies have examined the effects of intentional reworming, or self-treatment with helminths, on a variety of inflammation-related disorders. In this study, the latest results from ongoing socio-medical studies are described. The results point toward two important factors that appear to be overlooked in some if not most clinical trials. Specifically, (a) the method of preparation of the helminth can have a profound effect on its therapeutic efficacy, and (b) variation between individuals in the effective therapeutic dosage apparently covers a 10-fold range, regardless of the helminth used. These results highlight current limits in our understanding of the biology of both hosts and helminths, and suggest that information from self-treatment may be critical for clinical evaluation of the benefits and limits of helminth therapy.

Clean water is now very rare due to the increased water pollution causing many diseases. Heavy metals mainly lead from industrial waste i.e. batteries, cable sheaths, machinery manufacturing, shipbuilding, lead oxide and radiation protection is accountable & largely contributed lead in river and canal waters. Presence of lead in water is hazardous to life due to many reasons. It can cause cancer, weakness, anemia, kidneys, high blood pressure and nerve diseases. Inorganic lead is reported to me more dangerous than organic one. Industries including batteries, cable sheaths, machinery manufacturing etc. drains water that has soluble lead ranging from 200 – 500 mg/L. The safe limit of lead in water is about 0.015 mg/L. Pakistan is a country rich in minerals. It has about 3.5 MT of Kaolin (Clay) deposits situated at Nagar Parker region of Sindh, Pakistan. This indigenous material is being used to produce ceramic products and in paper making. Now we use this mineral source to remove lead from water by adsorption. Kaolin clay can be used as an adsorbent due to its unique structure. XRF technique is employed for clay characterization. Resultants will be analyzed by UV – Vis Spectrophotometry.

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

In this paper we use the conformable fractional derivative to discuss some fractional linear differential equations with constant coefficients. By applying some similar arguments to the theory of ordinary differential equations, we establish a sufficient condition to guarantee the reliability of solving constant coefficient fractional differential equations by the conformable Laplace transform method. Finally, we analyze the analytical solution for a class of fractional models associated with Logistic model, Von Foerster model and Bertalanffy model is presented graphically for various fractional orders and solution of corresponding classical model is recovered as a particular case.

Water mist systems (WMS) are used for evaporative cooling in public areas. The health risks associated with their colonization by opportunistic premise plumbing pathogens (OPPPs) is not well understood. To advance the understanding of the potential health risk of OPPPs in WMS, biofilm, water and bioaerosol samples (n = 90) from ten (10) WMS in Australia were collected and analyzed by culture and polymerase chain reaction (PCR) methods to detect the occurrence of 5 representative OPPPs: Legionella pneumophila, Pseudomonas aeruginosa, Mycobacterium avium, Naegleria fowleri and Acanthamoeba. P. aeruginosa (44%, n = 90) occurred more frequently in samples, followed by L. pneumophila serogroup (Sg) 2 - 14 (18%, n = 90) and L. pneumophila Sg 1 (6%, n = 90). A negative correlation between OPPP occurrence and residual free chlorine was observed except with Acanthamoeba ,rs (30) = 0.067, p > 0.05. . All detected OPPPs were positively correlated with water temperature. Biofilms contained higher concentrations of L. pneumophila Sg 2 - 14 (1000 – 3000 CFU/ml) in comparison to water samples (0-100CFU/ml). This study suggests that WMS can be colonized by OPPPs and are a potential health risk if OPPP contaminated aerosols get released into ambient atmospheres.

The exposure of people to opportunistic premise plumbing pathogens (OPPPs) such as Legionella, Mycobacterium and Pseudomonas in aerosolised water has been linked to opportunistic infections. Water mist systems (WMS) that are used to cool public places by flash evaporation of tiny water aerosols are gaining prominence in hot climatic regions of Australia. Their potential to be colonised by OPPPs has not been adequately studied. The public health impact of OPPPs is significant, as Legionella caused 63% of waterborne disease case hospitalisations in the United States associated with drinking water systems during 2013–2014, and the incidence of Mycobacterium avium over the same period was 647 cases per 100,000. As WMS are part of premise plumbing, they have structural characteristics that can promote biofilm formation, as well as the presence of free-living amoebae (FLA), low residual disinfection levels, elevated water temperatures and oligotrophic conditions, all of which can promote OPPP inhabitancy. This review highlights the potential public health risks of using WMS as a cooling intervention in public places and advocates for their regulation in places of public assembly and entertainment.

The United Nations Convention on the Rights of Persons with Disabilities (hereafter CRPD) has provided a radical imperative for the reform of mental health and capacity legislation around the world. The interpretation of the CRPD has been controversial, ranging from complete abolition of detention, forcible treatment and substitute decision making, to acceptance that elements of these measures need to be retained but based on non-discriminatory criteria, additional safe-guards and a comprehensive shift towards supported decision-making. While the potential ef-fects of the CRPD on mental health social work and social work generally are considerable given their shared commitment towards social justice, to date there has been no review of research evi-dence exploring their relationship. In addressing this knowledge gap, this study held a prelimi-nary discussion with practitioners and academics at the European Association of Social Work Mental Health Special Interest Group in Amsterdam 2022, followed by a scoping literature re-view on the question: What impact, if any, has the CRPD had on social work practice? The review produced four main findings: impact on legislation; positive impact on practice; limited impact on practice; and impact on social work education and research. In sum, while there were some positive indications of social work and mental health social work practice being influenced by the CRPD, these were scant. Barriers to change included tendencies among some social workers to practise substitute decision-making, in part related to resourcing and policy contexts, and under-standings of disability aligned to individualised/medical rather than social perspectives. The results indicate that legal reform on its own is insufficient to impact social work practice, and that realising the potential of the CRPD will necessitate good quality training, as well as improv-ing social workers’ knowledge of the human rights of people with mental impairment.

Globally, anthropogenic sound and artificial light pollution have increased to alarming levels. Evidence suggests that these can disrupt critical processes that impact ecosystems and human health. However, limited focus has been given to the potential effects of sound and artificial light pollution on microbiomes. Microbial communities are the foundations of our ecosystems. They are essential for human health and provide myriad ecosystem services. Therefore, disruption to microbiomes by anthropogenic sound and artificial light could have important ecological and human health implications. In this mini-review, we provide a critical appraisal of available scientific literature on the effects of anthropogenic sound and light exposure on microorganisms and discuss the potential ecological and human health implications. Our mini-review shows that a limited number of studies have been carried out to investigate the effects of anthropogenic sound and light pollution on microbiomes. However, based on these studies, it is evident that anthropogenic sound and light pollution have the potential to significantly influence ecosystems and human health via microbial interactions. Many of the studies suffered from modest sample sizes, suboptimal experiments designs, and some of the bioinformatics approaches used are now outdated. These factors should be improved in future studies. This is an emerging and severely underexplored area of research that could have important implications for global ecosystems and public health. Finally, we also propose the photo-sonic restoration hypothesis: does restoring natural levels of light and sound help to restore microbiomes and ecosystem stability?

In the century and a half since Maxwell first conjured his “finite being” which Lord Kelvin subsequently dubbed a “daemon”, researchers have explored the connections between non-equilibrium thermodynamics, entropy, and information theory. In recent years various Thermodynamic Uncertainty Relations (TURs) have been derived to inform upon the relationship between the entropy production and the precision possible in thermodynamic machines and processes. In this paper the recently derived TURs are applied to the hypothetical thermodynamic economy as described by Parker [1]. The TURs define the lower bound on the total entropy production of the economy. Changes in this entropy production rate has consequences on the stability of the economic system and plays a central role in the business cycle. This new perspective has important implications for policy makers, researchers, and other economic actors.

The Connor–Davidson Resilience Scale (CD-RISC) and the Brief Resilience Scale (BRS) are two widely used scales to measure resilience. Although both scales seek to assess an individual’s ability to recover from and adapt to disruptions or stressful events, they may capture different aspects of resilience. While the CD-RISC focuses on resources that can help individuals recover from and adapt to disruptions or stressful events, the BRS directly measures one’s ability to bounce back or be resilient. The aim of this study is to empirically examine the differences between the CD-RISC and the BRS. Two samples (n = 202, 246) consisting of undergraduate students from Taiwan were used. The results of confirmatory factor analysis show that the CD-RISC and the BRS are highly correlated but still distinct. The results of regression analyses show that the CD-RISC and the BRS have unique predictive effects on depression and life satisfaction. The research findings suggest that the CD-RISC and the BRS capture different aspects of resilience. For future research on resilience, researchers should pay attention to the differences between these scales and choose the one that most closely fits their research purpose.

Understanding and preventing the “great obstetrical syndromes” has been the focus of pregnancy research for decades. The combined global impact from these syndromes on maternal and perinatal morbidity and mortality is compounded by increased long-term risk of adverse health effects following pregnancy. Accumulating evidence indicates that conditions such as pre-eclampsia, fetal growth restriction, spontaneous preterm labour, and stillbirth, are syndromes with etiologic heterogeneity that share common pathophysiologic pathways involving placental dysfunction. Recently, the importance of the interaction between fetal and maternal genomes has been extended to include the epigenetic impact of pre-existing maternal pathophysiology on placental development and highlights the importance of nutritional and environmental factors in altered placentation. Validated first-trimester screening algorithms for preeclampsia can identify high-risk women and prophylactic treatment with low-dose aspirin can be initiated. High-risk women can be monitored during the second trimester using clinical assessment, ultrasound, and biochemical markers, that are able to predict complications prior to the development of clinical signs and symptoms. The integration of lifestyle interventions, pregnancy screening, and medical management represents a conceptual advance in pregnancy care. This approach has the potential to significantly reduce pregnancy complications, maternal and perinatal morbidity and mortality, adverse health outcomes later in life, and health-care costs.

Thermal interface material (TIM) that can exist as liquid at the service temperature enables efficient heat transfer across two adjacent surfaces in electronic applications. In this work, the thermal conductivities of different phase regions in the Ga-In system at various compositions and temperatures are measured for the first time. A modified comparative cut bar technique is used for the measurement of the thermal conductivities of In_xGa_1-x (x=0, 0.1, 0.214, 0.3, and 0.9) alloys at 40, 60, 80, and 100^oC that are the temperatures commonly encountered in consumer electronics. The thermal conductivity values for the liquid and semi-liquid (liquid+β) Ga-In alloys are higher than the TIM currently used in consumer electronics. These measured quantities, along with the available experimental data from the literature, served as input for the thermal conductivity parameter optimization using the CALPHAD (CALculation of PHase Diagram) method for the pure elements, solution phase, and two-phase region. A set of self-consistent parameters for the description of the thermal conductivity of the Ga-In system is obtained. There is good agreement between the measured and calculated thermal conductivity values for all the phases. Hence, it can be envisaged that liquid/semi-liquid Ga-In alloys can be considered as a potential TIM in consumer electronics due to its high thermal conductivity.

As the most commonly used hydrogel material in contact lenses, the amount of water in a lens affects its optical properties and comfort for the wearer. Therefore, an important challenge is to determine the safety and efficacy of contact lenses by accurately and non-destructively measuring the water content in real time. In this study, we demonstrate the accurate detection of water content in hydrogel contact lenses using a high-precision ATR format in a portable terahertz time-domain spectroscopy system. The technique can resolve small variations in the dielectric constant in solution, which is difficult to achieve with traditional transmission and reflection measurement modes. Information is obtained from the interaction between the sample and the swift waves propagating along the prism surface. The swift waves can excite longitudinal modes that are not directly accessible by conventional techniques. It is worth noting that the reference wave can be measured by removing the sample without disturbing the optical path. We also enhance the plasma effect at the interface with the hydrogel by using PVDF dielectric films of different polarities. We observed that the water content and refractive index changes in the ATR mode show different response patterns for nonpoled PVDF and poled PVDF membranes. This suggests that reflection and relative phase can be accurately evaluated in the THz-ATR technique, resulting in an accurate method for determining complex dielectric constants in the reflection geometry. This will allow accurate measurement of both surface and in vivo water content in hydrogels in the future and is a potential technical route for application in bioaqueous tissue measurements.

The estuarine exchange flow increases longitudinal dispersion of passive tracers and traps sinking particles, potentially creating an estuarine turbidity maximum (ETM): a localized maximum of suspended particulate matter concentration in an estuary. The ETM can have many implications - dead zones due to increased turbidity or hypoxia from organic matter decomposition, naval navigation challenges, and other water quality problems. Using timescales, we investigate how the interaction between exchange flow and particle sinking leads to ETMs by modeling a sinking tracer in an idealized box model of the Total Exchange Flow (TEF) first developed by Parker MacCready. Results indicate that the balance of particle sinking and vertical mixing is critical to determining ETM size and location. We then focus on the role of ecology in ETM formation through the use of The Peter-Parker Model: a new biophysical model which combines the TEF box model with a Nutrient-Phytoplankton-Zooplankton-Detritus (NPZD) model, the likes of which were first developed by Peter J.S. Franks. Detritus sinking rates similarly influence detritus peak concentration and location (an ETM), but detritus ETMs occur in a different location than the sinking tracer due to the influence of the biological factors which create a time lag of about 1 day. Lastly, we characterize the flow of the models with a dimensionless parameter that compares timescales and summarizes the dynamics of the sinking tracer in ETM formation and can be used across systems.

We exploit the properties of complex time to obtain an analytical relationship based on considerations of causality between the two conserved quantities of a system’s Hamiltonian and its Entropy Production. In natural units, when complexified, the one is simply the Wick-rotated complex-conjugate of the other. A Hilbert transform relation is constructed in the formalism of Quantitative Geometrical Thermodynamics which enables system irreversibility to be handled analytically within a framework that unifies both the microscopic and macroscopic scales, and which also unifies the treatment of both reversibility and irreversibility as complementary parts of a single physical description. In particular the thermodynamics of two unitary entities are considered: the alpha particle which is absolutely stable (that is, trivially reversible with zero entropy production), and a black hole whose absolute disequilibrium (unconditional irreversibility) is characterized by a non-zero entropy production for which we show an alternate derivation confirming our previous one (Universe 7, 2021, 325). The thermodynamics of a canonical decaying harmonic oscillator are also considered. In this treatment the complexification of time also enables a meaningful physical interpretation of both “imaginary time” and “imaginary energy”.

Double-spiral galaxies are common in the Universe. It is known that the logarithmic double spiral is a Maximum Entropy geometry and represents spiral galaxies well. It is also known that the virial mass of such a galaxy can be approximately determined from the entropy of its central supermassive black hole. But over time the black hole must accrete mass, and therefore the overall galactic entropy must increase. From the associated entropic Euler-Lagrange equation (forming the basis of the Principle of Least Exertion, and also enabling the application of Nöther’s theorem) we show that the galactic entropy production is a conserved quantity, and we derive an appropriate expression for the relativistic entropic Hamiltonian of an idealised spiral galaxy. We generalise Onsager’s celebrated expression for entropy production and demonstrate that galactic entropy production has two parts, one many orders of magnitude larger than the other, and where the smaller is comparable to the Hawking radiation of the central supermassive black hole. We conclude that galaxies cannot be isolated, since even idealised spiral galaxies have non-zero entropy production.

Many reported sea level records are often not a single measurement. They are then a composition of different records from several tide gauges. Sometimes, they are from the same tide gauge, but the tide gauge stability has been affected by earthquakes. This is the case of Guam as discussed in the present manuscript. The claimed sea level acceleration of Guam is only the result of two earthquakes that have compromised the stability of the tide gauge.

This work presents the computation of reliable warming trends for central Australia around Alice Springs within a circle of radius 1,000 km. Between 1880 and 2011, the average warming for the centre of Australia is +0.166 ºC/century, slightly smaller than the warming of Alice Springs, that is +0.176 ºC/century. Over a shorter time between 1910 and 2011, the centre of Australia is warming +0.794 ºC/century, slightly more than the warming of Alice Springs, that is +0.719 ºC/century.

We previously described spherical crystals in minerals from prismatine-bearing rock from Waldheim, including ultrahigh-pressure (UHP) minerals such as stishovite and coesite, in uncommon crustal environments. To determine if this was an outlier phenomenon, we searched for equivalent inclusions in other rocks, which we indeed discovered in a Variscan tin granite sensu stricto from the Erzgebirge. The identification of more examples of this phenomenon implies a novel, very rapid transcrustal transport mechanism, which however is not unique. We demonstrate the unusual occurrence of UHP minerals (moissanite, diamond, lonsdaleite, stishovite, coesite, kumdykolite, and cristobalite-II) in topaz of granitic rocks, which reflects the direct interaction of mantle and crust via supercritical fluids or extremely volatile-rich melts. Most UHP minerals are tiny inclusions in moissanite. The trapping by this mineral prevents a fast reaction in an extraneous environment.

The diagnosis and treatment of autoimmune diseases are major challenges. Their signs, symptoms, and their clinical severity change throughout the course of the disease. The available treatments for these conditions do not result in complete remission, and their long-term use generates several side effects. The main challenges in this field are the development of more sensitive diagnostic tools, and effective treatments. Studies in patients and animal models reported alterations in monocyte phenotype, activation, and function. These cells play an essential role in the pathogenesis of chronic inflammatory states and have become a target for extracorporeal monitoring and specific intervention. Nanoparticles (NPs) are ultrafine particles that can be used as contrast agents in diagnostic imaging techniques to detect specific cells in inflammatory infiltrates in tissues that are not easily accessible by biopsy. In addition, NPs can be designed to deliver drugs to a cell population or tissue. This review describes several experimental pieces of evidence demonstrating that monocytes and macrophages can specifically uptake various types of NPs, thus becoming detectable in vivo by magnetic resonance imaging and susceptible to be modulated by therapeutic agents. Hence, nanoparticles targeting mononuclear phagocytes represent promising tools for diagnosing and treatment.

This project focuses on using machine learning classification algorithms to determine whether two people are 6 feet apart or not. Two Raspberry Pis were used simulate smart phones. RSSI values of the Bluetooth beacons transmitted between the Raspberry Pis were collected and recorded to train the classifier. The Gaussian Support Vector Machine Classifer yielded the highest testing accuracy of 79.670 and the Decision Tree Classifier yielded the highest AUC of 0.80.

We summarize the results on electron transport in hybrid superconducting S/B/S' mesa-structure consisted of the oxide epitaxial S/B heterostructures, where S is the cuprate YBa2Cu3O 7-x superconductor, B – an interlayer with the spin dependent characteristics, and S’ is the Nb top superconductor. Josephson effect was observed manifested in appearance of oscillating Shapiro steps amplitudes with microwave signal power due to synchronization of junction self-generation of electromagnetic radiation and the external microwave probe signal. Triplet component of superconducting correlations emerged when the interlayer comprised two magnetic materials SrRuO3 and La0.7Sr0.3MnO3 with non-collinear magnetizations as well in the case of antiferromagnetic insulator Sr2IrO4 characterized by strong spin-orbit interaction. Thickness of the interlayer in the both cases considerably exceeded the coherence length of the magnetic spin active interlayer hinting on appearance of long-range proximity effect and spin-triplet superconducting current. Magnetic field dependences measured at dc, and the existence of the second harmonic in superconducting current–phase relation revealed by measurements at microwave frequencies will be discussed.

The Principle of Indifference (“PI”: the simplest non-informative prior in Bayesian probability) has been shown to lead to paradoxes since Bertrand (1889). Von Mises (1928) introduced the “Wine/Water Paradox” as a resonant example of a “Bertrand paradox”, and which has been presented as demonstrating that the PI must be rejected. We now resolve these paradoxes by a Maximum Entropy (MaxEnt) treatment of the PI that also includes information provided by Benford’s “Law of Anomalous Numbers” (1938). We show that the PI should be understood to represent a family of informationally-identical MaxEnt solutions; each solution being identified with its own explicitly justified boundary condition. In particular, our solution of the Wine/Water Paradox exploits Benford’s Law to construct a non-uniform distribution representing the universal constraint of scale invariance, which is a physical consequence of the Second Law of Thermodynamics.

Microbial Fuel Cells (MFCs) representing a promising technology for the extract of energy and resources through wastewater and it also offer an economic solution to the problem of environment effluent and energy crisis in near future. The advance device is rather appealing, due its potential benefits, its practical application is, however hindered by several drawbacks, such an internally competing microbial reaction, and low power generation. This report is an endeavor to address various design connected to the MFCs application to wastewater treatment, in particular cost effective bioelectricity from waste water are reviewed and discussed with a multidisciplinary approach. The conclusions drawn herein can be of practical interest to all new researchers dealing with effluent wastewater treatment using MFCs.

Hearing loss stands as the most prevalent sensory deficit among humans, posing a significant global health challenge. Projections indicate that by 2050, approximately 10% of the world's population will grapple with disabling hearing impairment. While approximately half of these cases have a genetic etiology, traditional interventions such as hearing aids and cochlear implants do not completely restore normal hearing. The absence of biological treatment has prompted significant efforts in recent years, with a strong focus on gene therapy to address hereditary hearing loss. Although several studies have exhibited promising recovery of common forms of genetic deafness in mouse models, existing challenges must be overcome to make gene therapy applicable in the near future. Herein, we summarize the primary gene therapy strategies employed over past years, provide an overview of the recent achievements in the preclinical studies for genetic hearing loss, and outline the current key obstacles to cochlear gene therapy.

This work presents emission line flux and kinematic structure mapping based on IFU data of the planetary nebulae Abell 30 (A30). The IFU has a field of view (FoV) of 16" x 12.3" and was used to partially cover knots J1 and J2, and completely cover knots J3 and J4 of A30. Our emission line flux map shows recombination species C II, C III, He I, O II as well as forbidden line species [O III], [Ne III] and [Ne IV] of high excitation level are all distributed in different parts of the knots. The kinematic structure shows considerable variation in both the velocities and spatial locations of these knots with positive and negative velocity excursions from the systematic value. Forbidden line species [O III], [Ne III] are distributed in both knots J3 and J4 but they are travelling at different speeds in opposite directions. Despite variation in distribution of the species, the velocities of [Ne IV] and [O III] are similar and travelling in the same direction while the other species [Ne III], He I, and O II share similar velocity of 200kms−1 up in the opposite direction. The complexity of distribution and kinematic structure of the knots revealed in this work indicates a strong tendency towards the hypothesis of multiple triggering events in the past history of A30.

Ovarian cancer is the most lethal gynecological malignancy. Poor overall survival, particularly for patients with high grade serous (HGS) ovarian cancer, are often attributed to late stage at diagnosis and relapse following chemotherapy. HGS ovarian cancer is a heterogenous disease in that few genes are consistently mutated between patients. Additionally, HGS ovarian cancer is characterized by high genomic instability. For these reasons personalized approaches may be necessary for effective treatment and cure. Understanding the molecular mechanisms that contribute to tumor metastasis and chemoresistance are essential to improve survival rates. One favored model for tumor metastasis and chemoresistance is the cancer stem cell (CSC) model. CSCs are cells with enhanced self-renewal properties that are enriched following chemotherapy. Elimination of this cell population is thought to be a mechanism to increase therapeutic response. Therefore, accurate identification of stem cell populations that are most clinically relevant is necessary. While many CSC identifiers (ALDH, OCT4, CD133, and side population) have been established, it is still not clear which population(s) will be most beneficial to targeted in patients. Therefore, there is a critical need to characterize CSCs with reliable markers and find their weaknesses that will make the CSCs amenable to therapy. Many signaling pathways are implicated for their roles in CSC initiation and maintenance. Therapeutically targeting pathways needed for CSC initiation or maintenance may be an effective way of treating HGS ovarian cancer patients. In conclusion, the prognosis for HGS ovarian cancer may be improved by combining CSC phenotyping with targeted therapies for pathways involved in CSC maintenance.

Resilience has been defined as one's competence to maintain a mental health state and overall well-being when undergoing grave stress or facing significant adversities. Numerous resili-ence-investigating research tools were developed over the years, with the Connor-Davidson Re-silience Scale (CD-RISC), a self-rated tool presenting valuable psychometric properties, remaining one of the most prominent. We aimed to translate and validate the brief CD-RISC-10 in a convenient sample of 584 nurses in Greece's secondary and tertiary health care system. We conducted a con-firmatory factor analysis and known-groups validity and estimated the reliability of the CD-RISC-10. Our confirmatory factor analysis revealed that the scale had a unifactorial structure since all the model fit indices were very good. Moreover, the reliability of the CD-RISC-10 was very good since Cronbach's alpha was 0.924 and McDonald's omega was 0.925. Therefore, the Greek version of the CD-RISC-10 confirmed the factor structure of the original one and had very good validity and reliability.

Polycystic ovary syndrome (PCOS) is increasingly recognized as a complex metabolic disorder that manifests in genetically susceptible women following a range of negative exposures to nutritional and environmental factors related to contemporary lifestyle. The hypothesis that PCOS phenotypes are derived from a mismatch between ancient genetic survival mechanisms and modern lifestyle practices is supported by a diversity of research findings. The proposed evolutionary model of the pathogenesis of PCOS incorporates evidence related to evolutionary theory, genetic studies, in-utero developmental epigenetic programming, transgenerational inheritance, metabolic features including insulin resistance, obesity and the apparent paradox of lean phenotypes, reproductive effects and subfertility, the impact of the microbiome and dysbiosis, endocrine disrupting chemical exposure, and the influence of lifestyle factors such as poor quality diet and physical inactivity. Based on these premises, the diverse lines of research are synthesized into a composite evolutionary model of the pathogenesis of PCOS. It is hoped that this model will assist clinicians and patients to understand the importance of lifestyle interventions in the prevention and management of PCOS and provide a conceptual framework for future research. It is appreciated that this theory represents a synthesis of the current evidence and that it is expected to evolve and change over time.

Polycystic ovary syndrome (PCOS) is increasingly being viewed as an evolutionary mismatch disorder that manifests in women after exposure to a range of lifestyle and environmental factors. Although there is ongoing debate regarding the pathogenesis, international guidelines recommend lifestyle treatment, with diet and exercise, as the first line of management in all women with PCOS. In addition, accumulating evidence suggests that environmental factors such as endocrine disrupting chemicals (EDC) may be involved in the pathogenesis of PCOS due to their known hormonal and metabolic effects. As a result, international professional bodies have recommended that all pregnant women be advised of the risks of EDC and that education programs be developed to inform health professionals. Microparticulate air pollution (MAP) is also a significant environmental exposure that has been associated with a variety of chronic diseases, including PCOS. We performed a systematic review of studies examining the relationship between MAP and PCOS using the PRISMA methodology. The review identified 214 records from PubMed, Cochrane, and Scopus databases, and 4 studies that met the inclusion criteria for qualitative assessment. Preliminary data suggest that MAP may contribute to the pathogenesis of PCOS via a number of mechanisms. This review highlights the need for greater awareness and further research on the effects of MAP in women with PCOS.

Physics has been thought to truly represent reality since at least Galileo, and the foundations of physics are always established using philosophical ideas. In particular, the elegant naming of physical entities is usually very influential in the acceptance of physical theories. We here demonstrate (using current developments in thermodynamics as an example) that both the epistemology and the ontology of physics ultimately rest on poetic language. What we understand depends essentially on the language we use. We wish to establish our knowledge securely, but strictly speaking this is impossible using only analytic language. Knowledge of the meanings of things must use a natural language designed to express meaning, that is, poetic language. Although the world is really there, and although we can indeed know it truly, this knowledge is never either complete or certain but ultimately must rest on intuition. Reading a recently discovered artefact with a palaeo-Hebrew inscription as from the first century, we demonstrate from it that this ontological understanding long predates the Hellenic period. Poetic language is primary, both logically and temporally.

We survey the main results emerging in the rapidly developing field that considers the geometry of thermodynamics and statistical mechanics. Our ideas of stability depend on variational principles – Maximum Entropy together with Least Action (and the isomorphic Least Exertion) – and this stability (invariance in time) indicates the centrality of the geometries of the systems. We explore a variety of examples of the application of thermodynamics in both macro- and micro-systems, and propose that irreversibility is an intrinsic and fundamental property of the physical realm (instead of being merely emergent). Using the concept of complex time, we examine the underlying mathematical unity of quantum mechanics, statistical mechanics, and geometrical thermodynamics. We show how the Planck and Boltzmann constants provide the fundamental quantum units for the phenomenological characteristics of the two Noether-conserved quantities controlling overall thermodynamic behaviour: respectively, energy and entropy production. We discuss the far-reaching isomorphisms (between all of complex time, temperature and the system symmetry) that always exist for Maximum Entropy systems, even as they exhibit either irreversible (dissipative, yet still dynamically stable) or reversible (including stable and static geometries) behaviours.

Vigorous early-season growth rate allows crops to compete more effectively against weeds and to conserve soil moisture in arid areas. Many crop species, including common bean, show genetic variation in growth rate between varieties. Despite this, the genetic basis of the early-season growth-related traits has not been well resolved in the species, in part due to historic phenotyping challenges. Using a range of UAV- and ground-based methods, we evaluated early-season growth vigor of two populations. These growth data were then used to find QTLs associated with several growth parameters. Our results suggest that early-season growth rate is the result of complex interactions between several genetic and environmental factors and highlight the need for the high-precision phenotyping provided by UAVs. The QTLs identified in this study are the first in common bean to be identified remotely using UAV technology and will be useful for developing crop varieties that compete with weeds more effectively. Ultimately, this will reduce crop losses and mitigate the need for herbicides and manual labor for weed control.

Recombinant laboratory plasmids (RLPs) are common in biological research and freely shared among academic research laboratories (ARLs), a practice required by many research funding agencies. However, the generation of accurate, reproducible results in experiments utilizing RLPs can be hampered by a lack of accompanying sequence information and metadata. This culture of RLP sharing without knowledge of sequence or etiology is accepted by publishers, not regulated by governments, and outside the realm of bio-industry. In addition, no centralized infrastructure currently exists to collate such data, which at the moment is fragmented across companies, non-profits, and governments and thus is not easily accessed or enacted toward threat assessment. The ubiquity, free exchange, and dual-use risk of RLPs exemplifies a biosecurity threat and elevates the need to characterize their composition to facilitate improved biorisk management by the academic community. A number of common sense solutions are available to create a culture that addresses the biosecurity gap posed by RLP sharing. Culture shift in RLP management will require new norms, effective data management for collation of RLP sequences and metadata, and an incentive structure that encourages sequencing by stakeholders. The next generation of researchers must initiate and champion this shift with support from funding agencies and endorsement from governments and international organizations. Coordination of efforts and stakeholders will require international public/private collaboration, a structure that will be critical to ensure widespread utility as well as the ability of lower-resourced partners to participate, contribute, and benefit.

Acetaminophen use during pregnancy and early childhood was accepted in the 1970s, but is now a subject of considerable concern. Careful analysis shows that initial acceptance of the drug was based on false assumptions and ignorance of the impact of the drug on brain development. Fourteen studies now indicate that prenatal exposure to acetaminophen is associated with neurodevelopmental problems. Based on corrections for confounding factors applied to the analyses of available data, it can be concluded that prenatal exposure to acetaminophen causes statistically significant risks of one subtype of autism spectrum disorder (ASD), developmental delays, and attention deficit hyperactivity disorder. In contrast, data regarding postnatal exposure to acetaminophen are limited, and several factors impede a classic multivariate analysis of data to resolve the issue. However, circumstantial evidence regarding postnatal exposure to the drug is abundant, and it can be concluded beyond a reasonable doubt that postnatal exposure to acetaminophen in susceptible children is responsible for many if not most cases of ASD. Circumstantial evidence includes at least three otherwise unexplained temporal relationships, data from laboratory animal studies, several miscellaneous and otherwise unexplained correlations, and the lack of alternative suspects that fit the evidence-derived profile.

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

The construction of optimized biological fuel cells requires a cathode which combines the longevity of a microbial catalyst with the power density of an enzymatic catalyst. Laccase secreting fungi were grown directly on the cathode of a biological fuel cell to facilitate the exchange of inactive enzymes with active enzymes with the goal of extending the lifetime of laccase cathodes. Additionally, a functionally graded coating was developed to increase enzyme loading at the cathode. Directly incorporating the laccase producing fungus at the cathode extends the operational lifetime of laccase cathodes while eliminating the need for frequent replenishment of the electrolyte. Additionally, the hybrid microbial-enzymatic cathode addresses the issue of enzyme inactivation by using the natural ability of fungi to exchange inactive laccases at the cathode with active laccases. Finally, enzyme adsorption was increased through the use of a functionally graded coating containing an optimized ratio of titanium dioxide nanoparticles and single walled carbon nanotubes. The hybrid microbial-enzymatic fuel cell combines the higher power density of enzymatic fuel cells with the longevity of microbial fuel cells and demonstrates the feasibility of a self-regenerating fuel cell in which inactive laccases are continuously exchanged with active laccases.

Children with central nervous system (CNS) malignancies often suffer from high symptom burden and risk of death. Pediatric palliative care is a medical specialty, provided by an interdisciplinary team, which focuses on enhancing quality of life and minimizing suffering for children with life-threatening or life-limiting disease, and their families. Primary palliative care skills which include basic symptom management, facilitation of goals-of-care discussions, and transition to hospice can and should be developed by all providers of neuro-oncology care. This chapter will review the fundamentals of providing primary palliative care

Maternal obesity and/or Western diet (WD) is associated with increased risk of metabolic dysfunction-associated steatotic liver disease (MASLD) in offspring, driven, in part, by dysregulation of the early life microbiome. Here, using a mouse model of WD-induced maternal obesity, we demonstrate that exposure to a disordered microbiome from WD-fed dams suppressed circulating levels of endogenous ligands of the aryl hydrocarbon receptor (AHR; indole, indole-3-acetate) and TMAO (a product of AHR-mediated transcription), as well as hepatic expression of Il10 (an AHR target), in offspring at 3 weeks of age. This signature was recapitulated by fecal microbial transfer from WD-fed pregnant dams to chow-fed germ-free (GF) lactating dams following parturition, and was associated with reduced abundance of Lactobacillus in GF offspring. Further, expression of Il10 was downregulated in liver myeloid cells and in LPS-stimulated bone marrow-derived macrophages (BMDM) in adult offspring, suggestive of a hypo-responsive, or tolerant, innate immune response. BMDMs from adult mice lacking AHR in macrophages exhibited a similar tolerogenic response, including diminished expression of Il10. Overall, our study shows that exposure to maternal WD alters microbial metabolites in the offspring that affect AHR signaling, potentially contributing to innate immune hypo-responsiveness and progression of MASLD, and highlights the impact of early life gut dysbiosis on offspring metabolism. Further investigations are warranted to elucidate the complex interplay between maternal diet, gut microbial function, and development of neonatal innate immune tolerance and potential therapeutic interventions targeting these pathways.

Alfalfa (Medicago sativa L.) is the most cultivated forage legume around the world. Under a variety of growing conditions, forage yield in alfalfa is stymied by biotic and abiotic stresses including heat, salt, drought, and disease. Given the sessile nature of plants, they use strategies such as differential gene expression to respond to environmental cues. Transcription factors control the expression of genes that contribute to or enable tolerance and survival during periods of stress. Basic-leucine zipper (bZIP) transcription factors have been demonstrated to play a critical role in regulating plant growth and development as well as mediate the responses to abiotic stress in several species, including Arabidopsis thaliana, Oryza sativa, Lotus japonicus, and Medicago truncatula. However, there is little information about bZIP transcription factors in cultivated alfalfa. In the present study, 237 bZIP genes were identified in alfalfa from publicly available sequencing data. Multiple sequence alignments showed the presence of intact bZIP motifs in the identified sequences. Based on previous phylogenetic analyses in Arabidopsis thaliana, alfalfa bZIPs were similarly divided and fell into 10 groups. The physicochemical properties, motif analysis, and phylogenetic study of the alfalfa bZIPs revealed high specificity within groups. The differential expression of alfalfa bZIPs in a suite of tissues indicates that particular bZIP genes are specifically expressed at different developmental stages in alfalfa. Similarly, expression analysis in response to ABA, cold, drought, and salt stresses, indicates that a subset of bZIP genes are also differentially expressed and likely play a role in abiotic stress signaling and/or tolerance. These expression patterns were further verified by qRT-PCR. However, further functional characterization of bZIP transcription factors in alfalfa will help illuminate the role they play in stress tolerance mechanisms in legumes and facilitate the molecular breeding of stress tolerance in alfalfa.

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

The process of testing software is examining the artifacts and behavior of the software under test by validating and verifying it. Testing can provide valuable information about the software. Given an input to the system, there is a challenge of distinguishing correct from potentially incorrect behavior, which is the test oracle problem. Although the combinatorial testing approach can effectively reduce the number of test cases, the manual inspection of the outputs is still required. In this paper, we propose an approach to automatically classify the return pages with conducting combinatorial testing based on page similarities and hierarchical clustering, by which potential output anomalies can be identified. In the experiment, we apply our approach to a real-world e-commerce website, an anomaly can be found with the visualization of the clustering hierarchy, which suggests the potential of the applicability of the approach.

Human endogenous retroviruses (HERVs) are ancient retroviral DNA sequences established into germline. They contain regulatory elements and encoded proteins few of which may provide benefits to hosts when co-opted as cellular genes. Their tight regulation is mainly achieved by epigenetic mechanisms which can be altered by environmental factors, e.g. viral infections, leading to HERV activation. Aberrant expression of HERVs associates with neurological disease, such as multiple sclerosis (MS) or amyotrophic lateral sclerosis (ALS), inflammatory processes and neurodegeneration. This review summarizes recent advances on the epigenetic mechanisms controlling HERV expression and the pathogenic effects triggered by HERV derepression. The article ends describing new promising therapies targeting HERV elements, one of which, temelimab, has completed phase II trials with encouraging results in treating MS. The information gathered here may turn helpful in the design of new strategies to unveil epigenetic failures behind HERV-triggered disease, opening new possibilities for druggable targets and/or for extending the use of temelimab to treat other associated diseases.

This study comprehensively evaluates the DNA/RNA Defend Pro (DRDP) sample collection buffer designed to inactivate and stabilize patient samples. The primary objectives encompassed assessing DRDP's efficacy in ensuring sample stability, facilitating extraction-free polymerase chain reaction (PCR), and ensuring compatibility with rapid antigen testing.Ninety-five diagnostic nasopharyngeal swab samples tested for influenza A/B, RSV A/B, and/or SARS-CoV-2 were diluted 1/10 with DRDP and anonymized. Stability testing involved incubating 31 positive samples at 4 °C, 20 °C, and 37 °C for 7 days, with regular extraction-free nucleic acid amplification testing (NAAT).Results demonstrated that DRDP guaranteed viral RNA stability at all temperatures for influenza, SARS-CoV-2 and RSV showing stability up to 7 days at 4 °C. DRDP-diluted samples exhibited robust compatibility with direct PCR, as 72 out of 88 samples positive for cobas Liat also tested positive for direct PCR. Non-concordant results could be explained by the 200-fold lower input in the extraction-free NAAT.Compared to NAAT, rapid antigen testing demonstrated lower sensitivity, as expected, while maintaining perfect specificity. Clear cutoffs between positive and negative rapid antigen testing results were observed in both cobas Liat and direct PCR analyses, validating DRDP's compatibility with these techniques. In conclusion, DRDP is an effective stabilizing medium compatible with direct PCR and rapid antigen testing and shows great potential for optimizing diagnostic processes, particularly in resource-limited or time-sensitive scenarios.

Chronic Traumatic Encephalopathy (CTE) is a neurodegenerative disease consistently associated with repetitive traumatic brain injuries (TBIs), which makes multiple professions, such as contact sports athletes, especially susceptible to its onset. There are currently no approved biomarkers to diagnose CTE, thus it can only be confirmed through a post-mortem brain autopsy. Several imaging and cerebrospinal fluid biomarkers have shown promise in the diagnosis. However, blood-based biomarkers can be more easily obtained and quantified, increasing their clinical feasibility and potential for prophylactic use. This article aimed to comprehensively review the studies into potential blood-based biomarkers of CTE, discussing common themes and limitations as well as suggesting future research directions. While the interest in blood-based biomarkers of CTE has recently increased, the research is still in its early stages. The main issue for many proposed biomarkers is their lack of selectivity for CTE. However, several molecules, such as tau phosphorylated on different epitopes, were able to discern CTE from different neurodegenerative diseases. Further, results from studies of exosomal biomarkers suggest that exosomes are a promising source of biomarkers reflective of the internal environment of the brain. Nonetheless, more longitudinal studies combining imaging, neurobehavioral and biochemical approaches are warranted to establish robust biomarkers of CTE.

Despite increased protection globally, climate change and other anthropogenic factors have caused a significant decline in seagrass cover. Identifying the specific causes of this decline is paramount if they are to be addressed. Therefore, we identified the causes of long-term change in seagrass/submerged aquatic vegetation (SAV) percentage cover and extent in the Bluefields Bay Special Fish Conservation Area (BBSFCA), a marine protected area on Jamaica’s southern coast. We used two random forest regression (RFr) models that included 2013 hydroacoustic survey SAV percentage cover data (dependent variable), and auxiliary data, reflectance data from level 2 processed 2013 Landsat 7 and 8 images and image band texture statistics maps (mean and variance) as predictors to generate 24 SAV percentage cover maps for the period 1984 – 2021 (37 years) using data from Landsat 4-5, 7 and 8 images., from which benthic features maps (SAV present, absent and coral reef) were created. Rainfall and map data were used to determine if SAV extent/area (km2) and average percentage cover and annual rainfall changed significantly over time and to evaluate the influence of rainfall. Rainfall impact on the overall spatial patterns of SAV loss, gain, and percentage cover change was assessed using a pixel-based regression. Finally, the most important spatial pattern predictors (two rainfall proxies (distance and direction from river mouth), benthic topography, depth, and hurricane exposure (a measure of hurricane disturbance)) of SAV loss, gain, and percentage cover change during 23 successive 1-to-4-year periods were identified using spatial Bayesian INLA generalized linear mixed models. SAV area/extent was largely stable with > 70% mean percentage cover for multiple years. However, Hurricane Ivan (in 2004) caused a significant decline in SAV area/extent (by 1.62 km2, or a 13%) during 2002 – 2006 and a second hurricane (Dean) in 2007 delayed recovery until 2015. Additionally, rainfall declined significantly by >1000 mm since 1901, and mean monthly rainfall positively influenced SAV percentage cover change. The pixel-based regression highlighted areas where mean monthly rainfall had a positive overall effect on SAV cover percentage change (across the entire bay) and gain (closer to the mouth of a river). The most frequently selected important spatial pattern predictors were the two rainfall proxies (areas closer to the river mouth were more likely to experience SAV loss and gain) and depth, with shallow areas generally having a higher probability of SAV loss and gain. Three hurricanes had significant but different impacts depending on their distance from the southern coastline. Hurricane Gilbert, which made landfall in 1988, resulted in higher SAV percentage cover loss in 1987 - 1988. Benthic locations with a northwestern/northern facing aspect (the predominant direction of Ivan’s leading edge wind bands) experienced higher SAV losses during 2002 – 2006. Although some locations impacted by Ivan and not by Dean recovered during 2006 – 2008, exposure to Ivan explained percentage cover loss during 2006 – 2008 and average exposure to (the cumulative impact of) Ivan and Dean (both with tracks close to the southern coastline) explained SAV loss during 2013 – 2015. Therefore, despite historic lows in annual rainfall, overall, higher rainfall was beneficial, multiple hurricanes impacted the site, and despite two hurricanes in three years SAV recovered within a decade. Hurricanes and a further reduction in rainfall may pose a serious threat to SAV persistence in the future.

The atomic structures of Zn and Na borophosphate glasses were studied by X-ray and neutron diffraction. Peaks assigned to the B−O, P−O, and O−O distances confirm that only BO4 units co-exist with the PO4 tetrahedra. The Zn−O and Na−O coordination numbers are found to be a little larger than four. The narrowest peaks of the Zn−O first-neighbor distances exist for the glasses along a line connecting the Zn(PO3)2 and BPO4 compositions (50 mol% P2O5) which is explained by networks of ZnO4, BO4, and PO4 tetrahedra with twofold coordinated oxygens. Calculated amounts of the available oxygen support this interpretation. Broadened peaks occur for glasses with lower P2O5 contents, consistent with the presence of threefold coordinated oxygens. The two distinct P−O peak components of the Zn and Na borophosphate glasses differ in their relative abundances which is interpreted by Na+ cations that coordinate oxygens in some P−O−B bridges, something not seen for the Zn2+ ions.

Background: This study investigated the incidence, characteristics and functional outcomes associated with unplanned Acute Care Unit Readmissions (ACUR) during inpatient traumatic brain injury (TBI) rehabilitation in an Asian cohort. Methods: Retrospective review of electronic medical records from single rehabilitation unit was conducted from 1 Jan 2012 to 31 Dec 2014. Inclusion criteria were first TBI, aged >18 years, admitted < 6 months of TBI. ACUR were characterized into either of neurological, medical or neurosurgical subtypes. The main outcome measure was discharge Functional Independence Measure (FIM). Secondary outcomes included rehabilitation length of stay (RLOS). Results: Of 121 eligible TBI records, the incidence of ACUR was 14% (n=17), comprising neurologic (76.5%) and medical (23.5%) subtypes, occurring at median of 13 days (IQR 6, 28.5) after rehabilitation admission. Patients without ACUR had significantly higher admission mean (SD) FIM score compared to those with ACUR (FIM ACUR-negative 63.4 (21.1) vs FIM ACUR-positive 50.53(25.4), P =0.026). Significantly lower discharge FIM was noted in those with ACUR compared to those without. (FIM ACUR-positive 65.8(31.4) vs FIM ACUR-negative 85.4 (21.1), P = 0.023) Furthermore, a significant near-doubling of RLOS was noted in ACUR patients compared to non-ACUR counterparts [ACUR-positive median 55 days (IQR 34.50, 87.50) vs ACUR-negative median 28 days (IQR 16.25, 40.00), P = 0.002]. Conclusion: This study highlights the significant negative functional impact and lengthening of rehabilitation duration of ACUR on inpatient rehabilitation outcome for TBI.

The field of domain adaptation, particularly in cross-domain sentiment classification, leverages labeled data from a source domain alongside unlabeled or sparsely labeled data from a target domain. The objective is to enhance performance in the target domain by mitigating the discrepancies in data distributions. Traditional methods in this area have focused on identifying and differentiating between pivotal sentiment words (shared across domains) and domain-specific sentiment words. In our work, we introduce a novel framework called Sentiment Domain Adapter (SDA), which incorporates a Category Attention Network (CAN) alongside a Convolutional Neural Network (CNN). This approach treats pivotal and domain-specific words as part of a collective category of attributes, which SDA learns to discern automatically, thereby enhancing domain adaptation. Additionally, SDA seeks to provide interpretative insights by learning these category attributes. Our model's optimization targets three main goals: (1) supervised classification accuracy, (2) minimizing the disparity in category feature distribution, and (3) maintaining domain invariance. Evaluations on three benchmark datasets for sentiment analysis affirm that SDA surpasses several established baselines.

The exploration and understanding of sentiments and emotions through textual analysis are foundational to advancements in natural language processing (NLP). While sentiment analysis, which involves discerning the polarity of text, has been extensively explored, the nuanced detection of complex emotions within textual content is still an emerging area of study. In this paper, we introduce EmoLeverage, a model leveraging Transformer architecture and enhanced with a novel Fusion Adapter module. This model aims to deepen emotion detection capabilities by drawing insights from fundamental sentiment analysis tasks, focusing exclusively on textual data. EmoLeverage sets a new standard in the field by demonstrating that deep, nuanced understanding of emotions is achievable through text alone, challenging and surpassing existing methodologies in emotion identification on key datasets. This is a significant step forward, considering the complexity of human emotions and the subtleties involved in their expression through language. By concentrating on textual input, EmoLeverage offers a promising avenue for applications where audio or visual data is not available, highlighting the versatility and potential of text-based emotional analysis. Our approach illustrates the untapped potential of leveraging sophisticated NLP techniques to enhance the detection and comprehension of a wide array of emotions from text. The success of EmoLeverage in outperforming conventional models in emotion recognition tasks underscores the model's effectiveness in parsing and understanding the intricate expressions of human emotions through linguistic cues alone. This achievement paves the way for more accurate, efficient, and nuanced emotion detection tools, potentially transforming various sectors by providing deeper insights into human emotional states through text.

Downwind odor characteristics can be very different depending upon the size of the upwind point-source, interim topography, and wind conditions. At one extreme, the downwind odor plume from a relatively large, confined animal feeding operation (CAFO), located on a flat open plain and under stable, near-straight-line wind conditions can be rather broad, sustained and predictable relative to a fixed receptor site downwind. In contrast, the plume from a small point-source (e.g., a roof vent stack) located on irregular topography and under rapidly shifting wind conditions can be intermittent and fleeting. These transient odor events can be surprisingly intense and offensive, in spite of their fleeting occurrence and perception. This work reports on efforts to optimize an environmental odor sampling strategy, which is optimized for the challenges of (1) sampling of such transient odor 'spikes' and (2) the prioritization of odors/odorants from multiple, closely co-located point-sources, under such transient event conditions. Protocol refinement has emerged by way of 2 environmental odor assessment projects which have been undertaken on behalf of the Missouri Department of Natural Resources. The challenge of transient odor events has been mitigated utilizing rapid, odor cued whole-air grab capture sampling into metalized-FEP gas sampling bags, followed by immediate adsorption transfer onto SPME fibers or sorbent tubes for stabilization during the shipment and storage interval between collection and final analysis. Initial results demonstrated approximately 11 fold increases in target odorant yields for 900 mL sorbent tube transfers from 2-3 second 'burst' odor event bag-captures, as compared to equivalent direct collections at the same downwind receptor location but during perceived (stable) odor 'lull' periods. Results-to-date targeting refinement and field trials of this integrated environmental odor assessment strategy are presented. Preliminary application targeting general odor sampling and point-source differentiation utilizing tracer gases is also presented.

Introduction: IFITM3, an innate immune protein linked to COVID-19 severity, has recently been identified as a novel γ-secretase modulator. Independent research has shown that IFITM3 may facilitate SARS-CoV-2 neurotropism in an ACE2-independent manner. In a previous study, we had detected perturbations in IFITM3 networks in both the CNS and peripheral immune cells donated by AD patients. The purpose of this study is to explore the transcriptomic evidence of the SARS-CoV-2 / IFITM3 / AD interplay, validating previous findings from our group. Methods: Exploratory analyses involved meta-analysis of bulk and single cell RNA data for IFITM3 and FYN differential expression. For confirmatory analyses, we performed gene set enrichment analysis (GSEA) on an AD gene signature from AD Consensus transcriptomics; using the Enrichr platform, we scrutinized COVID-19 datasets for significant, overlapping enriched biological networks. Results: Bulk RNA data analysis revealed that IFITM3 and FYN were differentially expressed in two CNS regions in AD: the temporal cortex (AD vs. Controls, adj.p-value=1.3e^-6) and the parahippocampal cortex (AD vs. controls, adj.p-value=0.012). Correspondingly, single cell RNA analysis of IFITM3 and FYN revealed that it was differentially expressed in neuronal cells donated from AD patients (astrocytes, microglia and oligodendrocyte precursor cells), when compared to controls. Discussion: IFITM3 and by extent FYN were found as interactors within biological networks overlapping between AD and SARS-CoV-2 infection. SARS-CoV-2-mediated FYN/IFITM3 induction would mechanistically result in increased Tau fibrilization and Aβ oligomerization. FYN recruitment by viral processes results in abrogation of both fusion of IFITM3 vesicles with lysosomes; immunoevasion, by FYN-mediated impairment of autophagy would then serve to promote impaired detoxification from Aβ, while propagating Tau pathology in an IFITM3-independent manner.

Foot pain related to the plantar fascia is common in adults regardless of athletic background. Many pathologies can lead to the diagnosis of plantar enthesopathy, but the most relevant to this case study is related to structural defects within the plantar fascia. Due to the variety and sometimes unclear etiology of plantar fasciosis, no single standard of care treatment protocol is recognized. Often, patients receive NSAIDs, night splints, taping, physical therapy, foot orthosis, and extracorporeal shock wave therapies. This study presents Wharton Jelly (WJ) tissue allografts as an additional intervention for patients who fail standard-care treatments. WJ allografts are applied to supplement connective tissue defects directly, unlike other therapies, which aim to reduce swelling and symptomatic pain. This retrospective study includes seven patients who have previously failed standard-of-care treatment. Each received extracorporeal pulse-activated therapy (EPAT), WJ, laser therapy, and an orthotic. Patient progress was tracked using a visual analog scale, 0-10 scoring, reported by the patient at the initial visit and approximately thirteen weeks following, reporting an average improvement of 50%. The study's limitations include a small cohort size and a non-blinded retrospective design. These promising results provide evidence for a more extensive, randomized study to define dosage protocols further and confirm safety and efficacy.

Google Trends data can be informative for infectious disease incidences, including Lyme disease. However, the use of Google Trends for predictive purposes is underutilized. In this study, we tested the ability of Google Trends search data to predict monthly state-level Lyme disease case counts in the United States. We requested Lyme disease data for the years 2010-2021. We downloaded Google Trends search data on terms for Lyme disease, symptoms of Lyme disease, and diseases with similar symptoms as Lyme disease. We built mixed negative binomial models based on a training dataset (2010-2016) and tested the models on a test dataset (2017-2021). A model was built for each search term and monthly lags of search terms were included as predictors. The highest performing models had high predictive ability, indicated by low Root Mean Squared Errors (RMSEs) and close association between observed and predicted case counts. The highest performing model was for the search term “Summer Flu”, which indicates low specificity of some of the terms. We outline challenges of using Google Trends data, including data availability and a mismatch between geographic units. We discuss opportunities for Google Trends data, including prediction of additional zoonotic diseases and incorporating environmental and companion animal data.

Polycystic ovary syndrome (PCOS) is a multisystem disorder that presents with a variety of phenotypes involving metabolic, endocrine, reproductive, and psychological symptoms and signs. Women with PCOS are at increased risk of pregnancy complications including implantation failure, miscarriage, gestational diabetes, fetal growth restriction, preterm labour, and preeclampsia (PE). This may be attributed to the presence of specific susceptibility features associated with PCOS before and during pregnancy, such as chronic systemic inflammation, insulin resistance (IR), and hyperandrogenism, all of which have been associated with an increased risk of pregnancy complications. Many of the features of PCOS are reversible following lifestyle interventions such as diet and exercise, and pregnant women following a healthy lifestyle have been found to have a lower risk of complications, including PE. This review summarizes the evidence investigating the risk of PE and the role of nutritional factors in women with PCOS. The findings suggest that the beneficial aspects of lifestyle management of PCOS, as recommended in the evidenced-based international guidelines, extend to improved pregnancy outcomes. Identifying high-risk women with PCOS will allow targeted interventions, early pregnancy screening, and increased surveillance for PE. Women with PCOS should be included in risk assessment algorithms for PE.

Viscoelastic testing (VET) by both TEG and ROTEM has demonstrated hypercoagulability early in Covid Associated Coagulopathy (CAC). Additional VET studies demonstrated fibrinolytic shutdown late in a majority of severely ill Covid-19 patients with associated elevation of D-dimer. Elevated d-dimer confirms that coagulation, followed by fibrinolysis, has occurred. These findings imply that, during CAC, three enzymes—thrombin, Factor XIIIa and plasmin—must have acted in sequence. However, limitations in standard VET analyses preclude exploration of the earliest phases of clot induction, as well as clot formation and clot dissolution in flowing blood. Herein we describe a novel method illuminating aspects of this unexplored area. In addition, we created an ex vivo blood flow model in which the interactions of thrombin, Factor XIII and plasmin with fibrinogen can be studied, allowing determination of Soluble Fibrin (SF), the highly unstable form of fibrin that precedes the appearance of a visible clot. This model allows determination of the SF level at which fibrin microclots begin to form and the length of time the resulting microclots persist under normal fibrinolytic attack. In addition, the flow model allows exploration of the late fibrinolytic shutdown that VET has previously demonstrated in CAC through standard methodology.

Gliomas are central nervous system (CNS) derived tumors that originate from glial cells and affect six per 100,000 people in the United States. They are the most common form of CNS neoplasm and are highly diffusely infiltrative to surrounding brain tissue. Gliomas of diffusive nature are classified into different subcategories: astrocytomas, oligodendrogliomas, and ependymomas. Computed tomography (CT) and Magnetic Resonance Imaging (MRI) are used to determine tumor category and spread which may dictate treatment options. This paper focuses on emerging treatments of chemotherapy management with temozolomide and Avastin as well as emerging immune modulation treatment with vaccinations, manipulation of cellular checkpoints CTLA-4 and PD-1, co-receptor modulation of neuropilin-1, CAR-T cell therapy, and CRISPR-Cas9 gene editing. The employment of TMZ and BEV has been supported in the literature, however, more research is necessitated to fully optimize regimens and to avoid immune- and toxicity-related effects of these drugs. Moreover, an even closer consideration is warranted for current immunotherapies as they are in their infancy compared to TMZ and BEV. Thus, although promising emerging treatment options, therapies involving cancer vaccines, ICIs, immune modulation of neuropilin-1, CAR-T, and CRISPR-Cas9 technology require further investigation into their long-term efficacy and utility in treating gliomas.

The virtually complete loss of intestinal worms, known as helminths, from Western society has resulted in elimination of a range of helminth-induced morbidities. Unfortunately, that loss has also led to inflammation-associated deficiencies in immune function, ultimately contributing to widespread pandemics of allergies, autoimmunity, and neuropsychiatric disorders. Several socio-medical studies have examined the effects of intentional reworming, or self-treatment with helminths, on a variety of inflammation-related disorders. In this study, the latest results from ongoing socio-medical studies are described. The results point toward two important factors that appear to be overlooked in some if not most clinical trials. Specifically, (a) the method of preparation of the helminth can have a profound effect on its therapeutic efficacy, and (b) variation between individuals in the effective therapeutic dosage apparently covers a 10-fold range, regardless of the helminth used. These results highlight current limits in our understanding of the biology of both hosts and helminths, and suggest that information from self-treatment may be critical in moving the field forward into mainstream medicine.

Head and neck squamous cell carcinoma (HNSCC) is a type of cancer that arises from the epithelium lining of the oral cavity, hypopharynx, oropharynx, and larynx. Despite advancement of the current treatment to HNSCC, such as surgery, chemotherapy, and radiotherapy, the overall survival rate of HNSCC remains poor due to late diagnosis and acquired resistance to treatment. Natural products have been extensively explored as a safer and more acceptable alternative to current treatments, with numerous studies displaying their potential against HNSCC. This review highlights preclinical studies in the past 5 years involving natural products against HNSCC and explores the signalling pathways altered by these products. This review also addresses challenges and future directions of the use of natural products as chemotherapeutic and chemoprevention agents against HNSCC.

The feasibility of using full ion kinetics, instead of gyrokinetics, in simulating low-frequency Ion-Temperature-Gradient (ITG) instabilities in tokamaks has recently been demonstrated by Sturdevant et al. [Physics of Plasmas 24, 081207 (2017)]. In that work, a variational integrator was developed to integrate the full orbits of ions in toroidal geometry, which proved to be accurate in capturing both the short-time scale cyclotron motion and long time scale drift motion. The present work extends that work in three aspects. First, we implement a relatively simple full orbit integrator, the Boris integrator, and demonstrate that the accuracy of this integrator is also sufficient for simulation of ITG instabilities. Second, the equilibrium magnetic configuration is extended to general toroidal configuration specified numerically, enabling simulation of realistic equilibria reconstructed from tokamak experiments. Third, we extend that work to the nonlinear regime and investigate the nonlinear saturation of ITG instabilities. To verify the new numerical implementation of the orbit integrator and magnetic configuration, the linear electrostatic ITG frequency and growth rate are compared with those given in Sturdevant's work and good agreement is found.

The common dry bean (Phaseolus vulgaris L.) is a nutrient dense food produced globally as a major pulse crop for direct human consumption, and is an important source of protein and micronutrients for hundreds of millions of people across Latin America, the Caribbean and Sub-Saharan Africa. Beans require large amounts of heat energy and time to cook, deterring consumers worldwide from purchasing beans. In regions where consumers rely on expensive fuelwood for food preparation, the yellow bean is often marketed as fast cooking. A Yellow Bean Panel (YBP) was assembled to explore the cooking time and health benefits of the five major seed types within the yellow bean market class (Amarillo, Canary, Manteca, Mayocoba, Njano) over two field seasons. This study shows how the Manteca yellow bean possess a fast cooking phenotype, which could serve a genetic resource for introducing fast cooking properties into a new generation of dry beans with cooking times < 20 minutes when pre-soaked and < 80 minutes unsoaked. Nutritional evaluation revealed fast cooking yellow beans have high iron retention (>80%) after boiling. An in vitro digestion/Caco-2 cell culture bioassay revealed a strong negative association between cooking time and iron bioavailability in the YBP (r values > -0.73). When either pre-soaked or left unsoaked the highest iron bioavailability scores were measured in the fast cooking Manteca genotypes providing evidence that this yellow market class is worthy of germplasm enhancement through the added benefit of improved iron quality after cooking.

Glaucoma poses a serious public health concern as it is the second leading cause of blindness after cataracts, while also being the leading cause of irreversible blindness worldwide. Glaucoma is more prevalent among Black, Latino, and Asian populations and it is essential to examine both racial and ethnic disparities that exist in treatment and prevention. As the number of people with glaucoma continues to grow, it is important to review aspects of this condition in order to better care for those affected. This article will review significant forms of glaucoma and what differentiates them in a diagnosis, treatment options, and recommendations on prevention and improving awareness

Background: Sudden changes in clinical practice and the altered ability to care for patients due to the COVID-19 pandemic have been associated with moral distress and mental health concerns in healthcare workers internationally. This study aimed to investigate the severity, prevalence, and predictors of moral distress experienced by Australian healthcare workers during the COVID-19 pandemic. Methods: A nationwide, voluntary, anonymous, single time-point, online survey of self-identified frontline healthcare workers was conducted between 27th August and 23rd October 2020. Participants were recruited through health organisations, professional associations or colleges, universities, government contacts, and national media. Results: 7846 complete responses were received from nurses (39.4%), doctors (31.1%), allied health staff (16.7%) or other roles (6.7%). Many participants reported moral distress related to resource scarcity (58.3%), wearing PPE (31.7%) limiting their ability to care for patients, exclusion of family going against their values (60.2%), and fear of letting co-workers down if they were infected (55.0%). Many personal and workplace predictors of moral distress were identified, with those working in certain frontline areas, metropolitan locations, and with prior mental health diagnoses at particular risk of distress. Moral distress was associated with an increased risk of adverse mental health outcomes. Feeling appreciated by the community mitigated this risk in healthcare workers. Conclusions: Safeguarding healthcare workforces during crises is important for both patient safety and workforce longevity. Targeted interventions are required to prevent or minimise moral distress and associated mental health concerns in healthcare workers during COVID-19 and other crises.

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

Accurate clinical diagnosis of patients presenting to primary care settings with acute sore throat remains challenging, often resulting in the over-prescribing of antibiotics. Using point-of-care tests (POCTs) to differentiate between respiratory infections is well-accepted, yet evidence on the application within primary care is sparse. We assessed the application of testing patients (n=160) from three family practices with suspected Streptococcal infections using rapid molecular tests (ID NOW Strep A2, Abbott). In addition to comparing clinical evaluation and prescription rates with either usual care or with testing, patients and staff completed a questionnaire about their experience of molecular POCT in primary care. The immediate availability of the result was important to patients (100%) and staff (≈90%) stated that molecular testing improved quality of care. Interestingly, only 22.73% of patients with a Centor score >2 tested positive for Strep A and overall, less than 50% of Centor scores 3 and 4 tested positive for Strep A with the ID NOW testing platform. The addition of rapid molecular POCTs to clinical assessment resulted in a 55- 65% reduction in immediate and deferred antibiotic prescriptions. The intervention was popular with patients and medical staff but was associated with increased cost and a longer appointment length.

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

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

More than 20 lines of independent evidence from clinical observations, studies in laboratory animal models, pharmacokinetic considerations, and numerous temporal and spatial associations previously indicate that numerous genetic and environmental factors leading to inflammation and oxidative stress confer vulnerability to aberrant metabolism of acetaminophen during early development, leading to autism spectrum disorder (ASD). Contrary to this conclusion, multivariate analyses of cohort data adjusting for inflammation-associated factors have tended to show little to no risk of acetaminophen use for neurodevelopment. To resolve this discrepancy, here we use in-silico methods to create an ideal (virtual) population of 120000 individuals in which 50% of all cases of virtual ASD are induced by oxidative stress-associated cofactors and acetaminophen use. We demonstrate that Cox regression analysis of this ideal data set shows little to no risk of acetaminophen use if cofactors which create aberrant metabolism of acetaminophen are adjusted for in the analysis. Further, under-reporting of acetaminophen use is shown to be a considerable problem for this analysis, leading to large and erroneously low calculated risks of acetaminophen use. In addition, we argue that factors which impart susceptibility to acetaminophen-induced injury, and propensity for acetaminophen use itself, can be shared between the prepartum, peripartum, and postpartum periods, creating additional difficulty in analysis of existing datasets to determine risks of acetaminophen exposure for neurodevelopment during a specific time frame. It is concluded that risks of acetaminophen use for neurodevelopment obtained from multivariate analysis of cohort data depend on underlying assumptions in the analyses, and that other evidence, both abundant and robust, demonstrate the critical role of acetaminophen in the etiology of ASD.

The present study aims to evaluate the capability of the TRMM-3B42-(V7) precipitation product to estimate appropriate precipitation rates in the Upper Indus basin (UIB) and the analysis of the dependency of the estimates’ accuracies on the time scale. To that avail statistical analyses and comparison of the TMPA- products with gauge measurements in the UIB are carried out. The dependency of the TMPA estimates’ quality on the time scale is analysed by comparisons of daily, monthly, seasonal and annual sums for the UIB. The results show considerable biases in the TMPA- (TRMM) precipitation estimates for the UIB, as well as high false alarms and miss ratios. The correlation of the TMPA- estimates with ground-based gauge data increases considerably and almost in a linear fashion with increasing temporal aggregation, i.e. time scale. The BIAS is mostly positive for the summer season, while for the winter season it is predominantly negative, thereby showing a slight over-estimation of the precipitation in summer and under-estimation in winter. The results of the study suggest that, in spite of these discrepancies between TMPA- estimates and gauge data, the use of the former in hydrological watershed modelling, endeavoured presently by the authors, may be a valuable alternative in data- scarce regions, like the UIB, but still must be taken with a grain of salt.

Biocultural heritage-based products, including regional specialty foods, are increasingly part of sustainable rural development strategies. While export-oriented biocultural products are often the most visible, we examine the role of campesino gastronomic heritage in the Central Valley of Tarija, Bolivia, as a case study of a local market-centered biocultural resource-based development strategy reflected in an alternative agri-food network. We develop a biocultural sustainability framework to examine this network from ecological, economic and sociocultural perspectives. Data are drawn from interviews (n=77), surveys (n=89) and participant observation, with primary and secondary producers of traditional and new products, as well as restaurant owners, market vendors and local consumers. We find that campesino biocultural heritage and the alternative agri-food network surrounding it represent an influential territorial project that underpins many household economies, particularly for women. We conclude that the relatively small investments by local governments to promote campesino gastronomic heritage are having positive ripple effects on small-scale producer livelihoods and on biocultural sustainability. We suggest that further support to increase market access and reduce other barriers to participation in alternative food networks will likely increase the options and benefits available to small-scale producers mobilising campesino gastronomic heritage within the local economy.

Protein malnutrition is present in developing countries but also in developed ones, due by the actual eating habits with insufficient protein intake, in addition to this it is estimated by the Food and Agricultural Organization of the United Nations an increase of world population of 9.1 billion people in less those 30 years, posing the challenge of nourish the mankind. There are different strategies to afford this challenge, one of the most promising ones is to approach novel protein sources like plants, microorganisms, and insects from dry lands.

Functional somatic disorders (FSD) characterized by persistent and disabling physical symptoms are common in adolescents. Diagnostic uncertainty and insufficient illness explanations are proposed perpetuating factors that may constitute barriers for treatment engagement. This study evaluates the impact of manualized assessment and psychoeducation on diagnostic certainty and various clinical outcomes in adolescents with multi-system FSD. Ninety-one adolescents (15-19 years) included in a randomized trial testing group-based therapy (AHEAD) received systematic assessment (4 hrs.) and a subsequent psychiatric consultation (1.5 hrs.). Clinical outcomes included self-reported physical health, symptom severity, illness perception, illness related behavior, and psychological flexibility assessed before and approximately two months after assessment, prior to specialized treatment. Data were analyzed using t-tests. Immediately following assessment 71 (80.7%) adolescents out of 88 reported a higher diagnostic certainty and 74 (84.1%) reported that attending assessment gave them positive expectations for future treatment. A clinically relevant improvement of physical health was not observed at two months but considerable reductions were seen on symptom severity, illness worry, negative illness perceptions, limiting illness behavior and psychological inflexibility. The results underpin the importance of systematic assessment and psychoeducation which may be effective in their own right in specialized treatment of adolescents with severe FSD.

Heel pain in the “funnel-shaped” space between the calcaneus, talus, and talocalcaneonavicular and subtalar joints may be representative of Sinus Tarsi syndrome. The pain is often characterized by a burning, numbness, or tingling sensation that can stem from strains and tears on the ligaments in that area. Injury treatment typically includes balance training, muscle exercises, bracing, foot orthosis, and non-steroidal anti-inflammatory drugs (NSAIDs). This study presents Wharton Jelly (WJ) tissue allografts as an alternative intervention for patients who fail standard-care treatments. WJ targets tissue defects, unlike other therapies, which aim to reduce swelling and symptomatic pain. This study includes five female patients who have previously failed standard-of-care treatment. Each received extracorporeal pulse-activated therapy (EPAT), WJ, laser therapy, and an orthotic. After an average of 80 days, the cohort had an overall 85.29% improvement in pain. The study's limitations include a small cohort size and a non-blinded design. Given the significant improvement in pain, WJ tissue allograft, combined with other techniques, presents an optimal patient care plan for tissue defects associated with Sinus Tarsi syndrome when standard-of-care treatments fail. These results provide evidence for a more extensive, randomized study to define dosage protocols further and confirm safety and efficacy.

Coronavirus Disease 2019 (COVID-19) has become a global health threat and has placed an extraordinary demand for healthcare workers around the world. In this study, we aim to examine the prevalence of burnout, its associating factors, and experience among Malaysian healthcare workers through an embedded mixed-method study design. We found that more than half of Malaysian health care workers in this sample experienced burnout. Direct involvement in COVID-19 screening or treatment, having a medical condition, and less psychological support in the workplace emerged to be the significant factors for personal-, work- and patient-related burnout. Participants described workload, uncertainties from the pandemic, challenged work-family balance and stretched workplace relationships as the sources of burnout. Exhaustion appeared to be the major symptom and many participants utilized problem-focused coping to deal with the adversities experienced during the pandemic. Participants reported physical, occupational, psychological, and social-related negative impacts emanating from burnout. As the pandemic trajectory is yet unknown, the findings provide early insight and guidance for possible interventions.

Like other organisms, fungi produce extracellular vesicles (EVs) that are involved in various biological processes, including intercellular communication and the transport of molecules between cells. These EVs can be applied in fungal pathogenesis, virulence, and interactions with other organisms, including host cells, in the case of fungal infections. While some types of mycoses are relatively common and easily treatable, certain neglected mycoses pose significant public health challenges, such as sporotrichosis, chromoblastomycosis, and paracoccidioidomycosis. These infectious diseases can cause significant morbidity and disability, leading to a reduced quality of life for the patients. So, research about the virulence factor is essential to understand how fungi escape the immune system. In this context, this manuscript reviews the study of fungi EVs, their cargo, their obtaining, and their role during the infectious process, which is extremely important for understanding this neglected mycosis.

Remediation of IT issues encoded into domain-specific or user-defined alerts occurring in cloud environments and customer ecosystems in a vast majority of cases suffers from accurate recommendations which could be timely supplied for recovery of performance degradations. That, of course, is hard to realize through furnishing those abnormality definitions with an appropriate expert knowledge which varies from one environment to another. At the same time, in a large proportion of support cases, the reported problems under Global Support Services (GSS) or Site Reliability Engineering (SRE) treatment ultimately go down to the product teams making them waste costly development hours on investigating self-monitoring metrics of our solutions. Therefore, the mean-time-to-resolution (MTTR) rates of problems/alerts are significantly impacted from lack of a systematic approach towards adopting AI Ops. That would imply building, maintaining, and continuously improving/annotating a data store of insights that ML models are trained and generalized across the whole customer base and corporate cloud services. Our ongoing study is in line with such a vision and validates an approach that learns the alert resolution patterns in such a global setting and explains them using interpretable AI methodologies. The knowledge store of causative rules is then applied in predicting potential sources of the application degradation reflected in an active alert instance. In this communication, we share our experiences with a prototype solution and up to date analysis demonstrating how root conditions are discovered with a high accuracy for a specific type of problem. It is validated against the historical data of resolutions performed by heavy manual development efforts. We also offer a Dempster-Shafer theory-based rule verification framework for experts as a what-if analysis tool to test their hypotheses about underlying environment.

Introduction: We describe the clinical features and inpatient trajectories of older adults hospitalized with COVID-19, and explore relationships with frailty. Methods: This retrospective observational study included older adults admitted as an emergency to a University Hospital who were diagnosed with COVID-19. Patient characteristics and hospital outcomes, primarily inpatient death or death within 14 days of discharge, were described for the whole cohort and by frailty status. Associations with mortality were further evaluated using Cox Proportional Hazards Regression (Hazard Ratio [HR], 95% Confidence Interval). Results: 214 patients (94 women) were included of whom 142 (66.4%) were frail with a median Clinical Frailty Scale (CFS) score of 6. Frail compared to non-frail patients were more likely to present with atypical symptoms including new or worsening confusion (45.1% vs 20.8%, p<0.001) and were more likely to die (66% vs 16%, p=0.001). Older age, being male, presenting with high illness acuity and high frailty were independent predictors of death and a dose-response association between frailty and mortality was observed (CFS 1-4: reference; CFS 5-6: HR 1.78, 95% CI 0.90, 3.53; CFS 7-8: HR 2.57, 95% CI 1.26, 5.24). Conclusions: Clinicians should have a low threshold for testing for COVID-19 in older and frail patients during periods of community viral transmission and diagnosis should prompt early advanced care planning.

This research paper presents a new application of electroactive polyimide doped with gold nanoparticles (PI/AuNPs) as a chemiresistor sensor for detecting hydrogen sulfide gas. The synthesis of PI/AuNPs was done in a simple 3-step process of polymerization using the as prepared amine-capped aniline trimer (ACAT), followed by imidization, and doping. Spectral analyses via FTIR, LC-MS and ¹H-NMR confirmed the formation of amine-capped aniline trimer with a MW of 288 g mol^-1. Comparison of ACAT, BSAA, and PI FTIR spectra showed successful polymerization of the last, while XRD validated the incorporation of metal nanoparticles onto the polymer matrix showing characteristic diffraction peaks corresponding to gold. Furthermore, TEM, and FE-SEM revealed the presence of well-dispersed Au nanoparticles with an average diameter of about 60nm. The electroactive PI/AuNPs-based sensor showed a sensitivity of 0.29% ppm^-1 H₂S at a linear concentration range of 50 to 300 ppm H₂S (r = 0.9777). The theoretical limit of detection was found at 0.142 ppm or 142 ppb H₂S gas. The sensor provided a stable response reading at an average response time of 43±5 seconds, which was easily recovered after an average time of 99±5 seconds. The sensor response was highly repeatable and reversible with RSD values of 8.88%, and 8.60%, respectively. Compared with the performance of the conventional conducting polyaniline also doped with gold nanoparticles (PANI/AuNPs), the fabricated electroactive PI/AuNPs exhibited improved sensing performance making it a potential candidate in monitoring H₂S in the environment and for work-related safety.

Solving environmental odor issues can be confounded by many analytical, technological, and socioeconomic factors. Considerable know-how and technologies can fail to properly identify odorants responsible for the downwind nuisance odor and mitigate it for the affected citizenry. We propose enabling solutions to environmental odor issues by utilizing troubleshooting techniques developed for the food, beverage, and consumer products industries. We showed that the downwind odorant impact-priority ranking process can be definable and relatively simple. The initial challenge is the prioritization of environmental odor character from the perspective of the impacted citizenry downwind. In this research, we aim at summarizing three natural models of the rolling unmasking effect (RUE) and discuss them more systematically in the context of the proposed downwind environmental odor prioritization approach. Regardless of the size and reach of an odor source, a simplification of odor character and composition typically develops with downwind dilution. The extreme odor simplification-upon-dilution was demonstrated for two plant varieties, prairie verbena and Virginia pepperweed. Their downwind odor frontal boundaries were dominated by single, character-defining odorants; p-cresol-dominated ‘barnyard’ odor, and benzyl mercaptan-dominated ‘burnt match’ odor, respectively. The P.T. porcupine downwind odor frontal boundary was dominated by two potent, character-defining odorants: (1) ‘onion’/‘body odor’ odorant #1 and (2) ‘onion’/‘grilled’ odorant #2. In contrast with their downwind boundary simplicities, each odor source presented considerable compositional complexity and composite character difference near the source. The proposed RUE approach’s ultimate significance is the illustration of naturally occurring phenomena that explain why some environmental odors and their sources can be challenging to identify and mitigate using the analytical only approach (focused on compound identities and concentrations). These approaches rarely move beyond comprehensive lists of compounds being emitted by the source.

The flux of opinions in newsletters and social media platforms significantly influences market perceptions regarding corporate entities and their financial instruments. This paper introduces an advanced model, the Sentiment Dynamics Analyzer (SDA), which leverages a refined hierarchical architecture of Transformers to effectively discern the sentiment embedded within financial texts, ranging from news headlines to microblogs. We have enhanced a RoBERTa model with specialized sentiment lexicons and an augmented layer of Transformer models tailored for nuanced sentence-level sentiment detection, aiming to assign a sentiment score from -1 to +1. Our evaluations demonstrate that SDA not only surpasses the previous best methods but also exhibits superior performance over robust baseline models. This success underscores the utility of integrating tailored contextual analyses with sector-specific sentiment insights in improving predictive accuracy.

Currently the bimatoprost implant (DURYSTA) is approved for a single administration secondary to concern for progressive corneal endothelial cell (CEC) loss with intracameral administration. In order to better understand the cause of CEC loss and other adverse events (AEs) with intracameral administration, multimodal imaging of the implant utilizing optical coherence topography (OCT), robotic ultrasound and bio microscopy video recording was utilized. Inherently the anterior chamber is a non-confined space. In certain examples the implant assumed a round and spotted structure as it picked up iris pigment as it migrated around the anterior chamber. Accordingly, we explored delivery of the implant in the middle segment behind the iris and in front of the pseudophakic lens. We then evaluated the suitability of various imaging modalities to assess the implant in this location. For middle segment administration, the ArcScan Insight 100 robotic ultrasound provided resolution and repeatability sufficient to monitor the implant behind the iris. This preliminary study hypothesizes that DURYSTA migration in the anterior chamber is the main source of AEs. Through use of a confined location, the middle segment, the implant is unlikely to migrate and cause CEC loss while also delivering drug closer to its site of action, the ciliary body. Further efforts are underway to understand the suitability of the middle segment for serial DURYSTA administration to maximize intraocular pressure lowering while minimizing AEs.

There are currently worldwide efforts to reduce sugar intake due to the various adverse health effects linked with the overconsumption of sugars. Artificial sweeteners have been used as an alternative to nutritive sugars in numerous applications; however, their long-term effects on human health remain controversial. This led to a shift in consumer preference towards non-caloric sweeteners from natural sources. Thaumatins are a class of intensely sweet proteins found in arils of the fruits of the West-African plant Thaumatococcus danielli. Thaumatins’ current production method through aqueous extraction from this plant and uncertainty of the harvest from tropical rainforests limits its supply while the demand is increasing. Despite successful recombinant expression of the protein in several organisms, no large-scale bioproduction facilities exist. We present preliminary process design, process simulation, and economic analysis for a large-scale (50 metric tons/year) production of thaumatin II variant by several different molecular farming platforms.

Background: Although widely believed to be safe for use in infants and children when used as directed, increasing evidence indicates that early life exposure to paracetamol (acetaminophen) may cause long-term neurodevelopmental problems. Further, recent studies in animal models demonstrate that cognitive development is exquisitely sensitive to paracetamol exposure during early development. In this study, evidence for the claim that paracetamol is safe was evaluated using a systematic literature search. Methods: Publications on PubMed between 1974 and 2017 that contained the keywords “infant” and either “paracetamol” or “acetaminophen” were considered. Of those initial 3096 papers, 218 were identified that made claims that paracetamol was safe for use with infants or children. From these 218, a total of 103 papers were identified as sources of authority for the safety claim. Results and Conclusions: A total of 52 papers contained actual experiments designed to test safety, and had a median follow-up time of 48 hours. None monitored neurodevelopment. Further, no trial considered total exposure to drug since birth, eliminating the possibility that the effects of drug exposure on long-term neurodevelopment could be accurately assessed. On the other hand, abundant and sufficient evidence was found to conclude that paracetamol does not induce acute liver damage in babies or children when used as directed.

The mineralocorticoid hormone aldosterone regulates sodium and potassium homeostasis but also adversely modulates the maladaptive process of cardiac adverse remodeling post-myocardial infarction. Through activation of its mineralocorticoid receptor (MR), a classic steroid hormone receptor/transcription factor, aldosterone promotes inflammation and fibrosis of the heart, the vasculature, and the kidneys. This is why MR antagonists reduce morbidity and mortality of heart disease patients and are part of the mainstay pharmacotherapy of advanced human heart failure. A plethora of animal studies using cell type–specific targeting of the MR gene have established the importance of MR signaling and function in cardiac myocytes, vascular endothelial and smooth muscle cells, renal cells, and macrophages. In terms of its signaling properties, the MR is distinct from nuclear receptors in that it has, in reality, two physiological hormonal agonists: not only aldosterone but also cortisol. In fact, in several tissues, including in the myocardium, cortisol is the primary hormone activating the MR. There is a considerable amount of evidence indicating that the effects of the MR in each tissue expressing it depend on tissue- and ligand-specific engagement of molecular co-regulators that either activate or suppress its transcriptional activity. Identification of these co-regulators for every ligand that interacts with the MR in the heart (and in other tissues) is of utmost importance therapeutically, since it can not only help elucidate fully the pathophysiological ramifications of the cardiac MR`s actions but also help design and develop novel better MR antagonist drugs for heart disease therapy. Among the various proteins the MR interacts with are molecules involved in cardiac G protein-coupled receptor (GPCR) signaling. This results in a significant amount of crosstalk between GPCRs and the MR, which can affect the latter`s activity dramatically in the heart and in other cardiovascular tissues. This review summarizes the current experimental evidence for this GPCR-MR crosstalk in the heart and discusses its pathophysiological implications for cardiac adverse remodeling as well as for heart disease therapy. Novel findings revealing non-conventional roles of GPCR signaling molecules, specifically of GPCR-kinase (GRK)-5, in cardiac MR regulation are also highlighted.

This research investigates the application of Fused Filament Fabrication (FFF) in producing WC-10Co hardmetals, focusing binder formulations and understanding its influence on extrusion force and the influence of printing variables on green density of the samples. By examining the interplay between different binder compositions and backbone contents, the study aims to enhance the mechanical properties of the sintered parts while reducing defects inherent in the printing process. Evidence suggested that formulated feedstocks influenced the hardness of the sintered hardmetal, not due to microstructural changes but to macrostructural responses like macro defects introduced during printing, debinding and sintering of the samples. The results demonstrate the critical role of PP-MA content in improving part density and sintered hardness, suggesting the need for specific thermal debinding protocols tailored to each feedstock. The study provides insights into the formulation of feedstocks for hardmetal FFF, proposing a path toward refining manufacturing processes for better quality and performance of 3D printed hardmetal components.

Curcumin, found in the rhizome of turmeric, has extensive therapeutic promises via its antioxidant, anti-inflammatory, and antiproliferative properties. Preclinical in vitro and in vivo data have shown curcumin to be an effective treatment for multiple cancers. These effects are drived by curcumin's ability to induce G2/M cell cycle arrest, induction of autophagy, activation of apoptotic pathways, disruption of molecular signaling, inhibition of invasion and metastasis, and by increasing the efficacy of existing chemotherapeutics. Here we focused on the hormetic behaviour of curcumin. Frequently, low doses of toxins and other stressors not only are harmless but also activate an adaptive stress whereas high dose activates acute responses like autophagy and cell death. This phenomenon is referred to as hormesis. Many molecules that cause cell death elicite an initial autophagic step that is a cytoprotective mechanism relying on elimination of dysfunctional structures intracellular, notably by mitophagy. This phenomenon is considered as a primarily protective mechanism against stressors. At higher doses, cells undergo mitochondrial outer membrane permeabilization due to calcium release from the endoplasmic reticulum and die. Herein, we address the complex crosstalk between the induced mitochondrial biogenesis, mitochondrial destabilization accompanied by mitophagy and cell death that can also be at play.

In this study, ignition delay and burning rate are experimentally investigated in relation to the effect of pristine carbon nanotubes (CNTs), sodium dodecylbenzene sulfonate (SDBS), and diesel blends. Single droplet combustion tests were conducted in a combustion system for 21 days using CNTs at concentrations of 50 ppm and 100 ppm, that were dispersed in Colombian commercial diesel and stabilized by SDBS. Additionally, recordings of the combustion were collected, and the Shadowgraph optical method was utilized for monitoring the evolution of droplet size during combustion. The measurements were done over a four-week period. The results demonstrated that the temporal stability has a direct impact on the single droplet combustion tests because a concentration of CNTs of 100 ppm showed higher stability than those achieved by 50 ppm. Consequently, improvements were found with a concentration of 100 ppm, for instance, thermal conductivity increased by about 20%, ignition delay time by 16.2%, and burning rate by 30.5%.

Although child-centred care is increasingly referred to within the nursing literature, a clear definition of child-centred care and clarity around the concept is yet to be achieved. The objectives of this review were to examine: 1) What constitutes the concept of child-centred care in healthcare? 2) How has the concept of child-centred care developed? 3) What is the applicability of child-centred care and what are its limitations? and 4) How does the concept of child-centred care benefit and inform children’s healthcare? In total, 2984 papers were imported for screening, following removal of duplicates and screening, 21 papers were included in the scoping review.The findings suggest that child-centred care is an emerging, ambiguous, poorly defined concept; no clear consensus exists about what constitutes child-centred care. Although it seems antithetical to argue against child-centred care, little robust evidence was identified that demonstrates the impact of, and benefit from, child-centred care. If child-centred care is to be a sustainable, convincing model to guide practice and compete with other models of care it needs to establish robust evidence of its effectiveness, impact on children and their families as well as the wider impacts on the healthcare system.

Splenic micronodular T-cell/histiocyte-rich large B-cell lymphoma is possibly derived from nodal T-cell/histiocyte-rich large B-cell lymphoma; however, a transition between the nodal and splenic micronodular forms has not been described to date. Of note, the only lymph nodes to be involved in association with the splenic micronodular pattern of the disease are the splenic hilar lymph nodes, and that, with partial involvement only. Kan et al, in their series of articles, have raised the possibility that corticosteroids, when prescribed prior to splenectomy, cause histopathological and functional modulations (apoptosis, necrosis, tissue shrinkage), which modify or even obscure the diagnostic morphological features. The indications for glucocorticoid therapy are either related to the suspected lymphoma, or else to other comorbidities, like asthma and autoimmune disorders. We propose that patients with the splenic, rather than nodal subset of the disease are likely to have been prescribed corticosteroids prior to histopathologic examination of the involved tissue, causing disparate morphologies in the spleen. Apoptosis, as induced by corticosteroids, is hypothesized as the major mechanism initiating the histopa-thological and functional changes in the splenic micronodular variant of our patients.

Background: Throughout the COVID-19 pandemic, hospital medical staff (HMS) have faced significant personal, workplace, and financial disruption. Many have experienced psychosocial burden, exceeding already concerning baseline levels. This study examines the types and predictors of coping strategies and help-seeking behaviours utilised by Australian junior and senior HMS during the first year of the pandemic. Methods: A cross-sectional online survey of Australian frontline healthcare workers was conducted between 27th August and 23rd October 2020. Data collected included demographics, personal and workplace disruptions, self-reported and validated mental health symptoms, coping strategies, and help-seeking. Results: The 9518 participants included 1966 hospital medical staff (62.1% senior, 37.9% junior). Both groups experienced a high burden of anxiety, depression, post-traumatic stress disorder, and burnout. Coping strategies varied by seniority, with maintaining exercise the most common strategy for both groups. Adverse mental health was associated with increased alcohol consumption. Engagement with professional support, although more frequent among junior staff, was uncommon in both groups. Conclusions: Junior and senior staff utilised different coping and help-seeking behaviours. Despite recognition of symptoms, very few HMS engaged formal support. The varied predictors of coping and help-seeking identified may inform targeted interventions to support these cohorts in current and future crises.

Social plasticity, defined as the ability to adaptively change the expression of social behavior according to previous experience and to social context, is a key ecological performance trait that should be viewed as crucial for Darwinian fitness. The neural mechanisms for social plasticity are poorly understood, in part due to skewed reliance on rodent models. Fish model organisms are relevant in the field of social plasticity for at least two reasons: first, the diversity of social organization among fish species is staggering, increasing the breadth of evolutionary relevant questions that can be asked. Second, that diversity also suggests translational relevance, since it is more likely that “core” mechanisms of social plasticity are discovered by analyzing a wider variety of social arrangements than relying on a single species. We analyze examples of social plasticity across fish species with different social organizations, concluding that a “core” mechanism is the initiation of behavioral shifts through the modulation of a conserved “social decision-making network”, along with other relevant brain regions, by monoamines, neuropeptides, and steroid hormones. The consolidation of these shifts may be mediated via neurogenomic adjustments and regulation of the expression of plasticity-related molecules (transcription factors, cell cycle regulators, and plasticity products).