Background—In 2011, Miller and Goldman published a study in Human and Experimental Toxicology that found a counterintuitive, positive correlation, r = 0.70 (r² = 0.49, p < .0001), demonstrating that as nations require more vaccine doses for their infants, infant mortality rates (IMRs) tend to increase (worsen). The dataset (n = 30) included the United States, a nation that required the most vaccines for their infants, and all nations with better IMRs than the United States. Dr. E. Bailey, a professor at BYU, and her students, recently read the Miller-Goldman study and found it "troublesome that this manuscript is in the top 5% of all research outputs" and falsely claimed that its findings were due to "inappropriate data exclusion," i.e., failure to analyze the "full dataset" of all 185 nations. The "Bailey reanalysis," titled Infant vaccination does not predict increased infant mortality rate: correcting past misinformation, was posted to the medRxiv preprint server on September 10, 2021 (version 1) and October 5, 2021 (version 3) and Europe PMC preprint server on September 10, 2021. Objective—This present study examines the various claims postulated by the Bailey reanalysis and assesses the robustness of their methodology, analyses, and reported results and conclusions. Methods—Data discussed in this paper are based on the previously mentioned study by Miller and Goldman and the Bailey reanalysis. Results—Linear regression analysis of IMR and the number of vaccine doses for each country yield a statistically significant positive correlation of r = 0.70 (p < .0001) for the top nations (n = 30) chosen by Miller-Goldman and r = 0.16 (p < .04) for the "entire dataset" chosen by Bailey et al (n = 185). Bailey also conducted linear regression analyses (for the year 2019) of IMRs as a function of vaccination rates for each of eight different vaccines and reported statistically significant inverse correlations for 7 of 8 vaccines over the entire range of vaccination rates. However, Miller and Goldman reanalyzed the Bailey analyses for nations with vaccination rates below 60% and found no statistically significant correlation for six vaccines (DPT, Hib, hepatitis B, polio, rotavirus, and measles) and statistically significant positive correlations for tuberculosis (r = 0.8, p < .005) and pneumococcal (r = 0.6 p < .023) vaccines. Conclusions—Bailey’s reanalysis corroborates a statistically significant positive correlation originally reported by Miller and Goldman. However, Bailey’s reported correlation (r = +0.16, p < .04) is small, likely due to poor methodology (failing to account for covariates, i.e., disparities among numerous socioeconomic factors that add uncertainty to their conclusion). The r-value reported by the Bailey reanalysis demonstrates an effect size that is about one-fourth (0.16/0.70) that reported by Miller-Goldman—underscoring how critically important it is for Bailey's reanalysis to eliminate confounding variables. Moreover, Bailey’s linear regression analyses of IMR as a function of vaccination rates for each of eight different vaccines demonstrate that some countries with low vaccination rates have low IMRs, while other countries with high vaccination rates have high IMRs. Rather than supporting a strong inverse correlation, the Bailey reanalysis demonstrates high vaccination rates are neither necessary nor sufficient to cause low IMR.

From their discovery in 2002, BRAF mutations have been identified as clear drivers of oncogenesis in several cancer types. Currently, their incidence rate is nearly 7% of all solid tumors with BRAF V600E constituting approximately 90% of these diagnoses [1]. In melanoma, thyroid cancer, and histiocytic neoplasms, BRAF hotspot mutations are found at a rate of about 50%, while in lung and colorectal cancers they range from 3 to 10% of reported cases [2-5]. Though present in other malignancies such as breast and ovarian cancers, they constitute a small portion of diagnoses (<1%). Given their frequency along with advancements in screening technologies, various methods are used for the detection of BRAF-mutant cancers. Among these are targeted next-generation sequencing (NGS) on tumor tissue or circulating tumor DNA (ctDNA) and immunohistochemistry (IHC)-based assays. With advancements in detection technologies, several approaches have been taken for the treatment of BRAF mutant cancers. In this review we retrace the milestones that led to the clinical development of targeted therapies currently available for these tumors.

We present an ontology log-OLOG- representation of the classical Miller-Urey experiment, usually considered as a paradigm for spontaneous generation of biomolecules on the prebiotic Earth and also, as a key in understanding the chemical evolution phenomena linked to the origins of life. Ologging The Miler-Urey experiment enables us, through the categorical notion of fibre product or pullback, to define the concept of Biogenic Space, as a space containing low complexity biogenic units subjected to appropriate physical and chemical conditions, facilitating the synthesis of highly complex organic molecules. Also, we characterize the Biogenic Space as a concrete universal object that could be associated with the preconditions for life inside various structures in the universe such as exoplanets and exomoons located in habitable zones, but also in interstellar and intergalactic organic clouds.

Miller Fisher Syndrome (MFS) is a rare variant of Guillain-Barré Syndrome (GBS). It is largely a clinical diagnosis based on the classical features of ataxia, areflexia, and opthalmoplegia. Its clinical evolution is most often favorable. However, other neurological signs and symptoms may also be present. Supportive laboratory studies (positivity of antibodies, CSF albumin-cytological dissociation and nerve conduction studies) are useful especially in uncommon presentations. We report a case of a 74-year-old patient who exhibited dysphonia and difficulty to swallowing previously to the classic triad of ataxia, areflexia, and opthalmoplegia, characteristic of MFS. CSF analysis demonstrates an albumin-cytological dissociation but anti-GQ1b antibody were negative. The patient has spontaneously and completely recovered after several weeks.

The “Crisis of Reproducibility” has received considerable attention both within the scientific community and without. While factors associated with scientific culture and practical practice are most often invoked, I propose that the Crisis of Reproducibility is ultimately a failure of generalization with a fundamental scientific basis in the methods used for biomedical research. The Denominator Problem describes how limitations intrinsic to the two primary approaches of biomedical research, clinical studies and pre-clinical experimental biology, lead to an inability to effectively characterize the full extent of biological heterogeneity, which compromises the task of generalizing acquired knowledge. Drawing on the example of the unifying role of theory in the physical sciences, I propose that multi-scale mathematical and dynamic computational models, when mapped to the modular structure of biological systems, can serve a unifying role as formal representations of what is conserved and similar from one biological context to another. This ability to explicitly describe the generation of heterogeneity from similarity addresses the Denominator Problem and provides a scientific response to the Crisis of Reproducibility.

California and most other coastlines around the world are being impacted by both long-term sea-level rise and short-term extreme events. Because of California’s long and intensively developed coastline, it is an important area for evaluating responses to these challenges. The predominant historic approach to coastal erosion in California and globally has been the construction of hard coastal armoring such as seawalls and rock revetments. The concept of living shorelines – defined as using natural elements like plants, sand or rocks to stabilize the coastline – has been widely proposed as a soft or green response to coastal erosion and flooding. These approaches have very limited application in high-energy environments, however, such as California’s 1,100-mile-long outer coast and are not realistic solutions for protection from wave attack at high tides or long-term sea-level rise. Each of the state’s coastal communities need to identify their most vulnerable areas, develop adaptation plans, and plan eventual relocation strategies in response to an accelerating sea-level rise.

The Environmental interactions contributed to the processes of settlement and development of the first settlers at southern Peru 15,000 BC. The determination of this process is based on paleoclimatic studies at southern Peru and ethnoarchaeological evidence. The determination of this process is based on paleoclimatic studies of southern Peru and ethnoarchaeological evidence; establishing as a result of this analysis the hypothesis of environmental interaction and territorial occupation of the first hunter-gatherer populations until their consolidation, dominating the geographical space from Tacna. The Disruptive disaster events and their effects on climate during the Peruvian Paleolithic resulted in the origin of local societies that shaped the Tiawanaku societies of the early horizon at Southern Peru and Northern Chile.

Although different assessments and evaluations of Dual-Miller cycle performed, specified output power and thermal performance associated with engine determined. Besides, multi objective optimization of thermal efficiency, Ecological Coefficient of performance ( ) and Ecological function ( ) by the mean of NSGA-II technique and thermodynamic analysis performed. The Pareto optimal frontier obtaining the best optimum solution is chosen by fuzzy Bellman-Zadeh, LINMAP, and TOPSIS decision-making techniques. Based on the results, performances of dual-Miller cycles and their optimization are improved.

Aymaraism, as a socio-cultural phenomenon, has given rise to components and elements of representativeness in the population of the Andes. However, the dialectic component of the Aymara as a nation is annulled by fundamental historiographical elements that underlie this process of identification. The empirical analysis of the historical data leads us to conclude that the Aymara language and culture contain ambiguous elements that cannot be defined according to the dialectical interpretation and the current narrative. Thus, the analysis of the cultural, linguistic and social elements of this population from the Early Horizon period to the present confirms the historical distortion towards a narrative component of origin and presence in the territory of the Qullasuyu, in the current geographical area of the Collao. In order to understand this phenomenon, this work promotes the complementarity of the analysis through the use of ethnoarchaeological and documentary elements in order to clarify the origin, synthesis and development of the Aymara from a historical perspective, leaving aside the dialectical component of the present.

The use of endophytic microbes is increasing in commercial agriculture. This review will describe the endophyte-plant relationship and the fungi and bacteria involved. Their abilities to alleviate biotic (diseases and pests) and abiotic stresses (drought, salt and flooding), remediate pollution and increase photosynthetic capabilities will be described. Their mechanisms of action will be elucidated. These frequently result in increased plant yields. Finally, methods and practices for formulation and commercial use will be described.

We develop an optimized force-field for poly(3-hexylthiophene) (P3HT) and demonstrate its utility for predicting thermodynamic self-assembly. In particular, we consider short oligomer chains, model electrostatics and solvent implicitly, and coarsely model solvent evaporation. We quantify the performance of our model to determine what the optimal system sizes are for exploring self-assembly at combinations of state variables. We perform molecular dynamics simulations to predict the self-assembly of P3HT at ~350 combinations of temperature and solvent quality. Our structural calculations predict that the highest degrees of order are obtained with good solvents just below the melting temperature. We find our model produces the most accurate structural predictions to date, as measured by agreement with grazing incident X-ray scattering experiments.

Ante-mortem bovine tuberculosis (bTB) tests for buffaloes include the single comparative intradermal tuberculin test (SCITT), interferon-gamma (IFN-γ) release assay (IGRA) and IFN-γ-inducible protein 10 release assay (IPRA). Although parallel test interpretation increases detection of Mycobacterium bovis-infected buffaloes, these algorithms may not be suitable for screening buffaloes in historically bTB-free herds. In this study, the specificities of three assays were determined using M. bovis unexposed herds, and a high specificity diagnostic algorithm developed. Serial test interpretation using the IGRA and IPRA showed significantly greater specificity (98.3%) than individual tests or parallel testing (73%). When the SCITT was added, the algorithm had a 100% specificity. Since the cytokine assays had imperfect specificity, potential cross-reactivity with nontuberculous mycobacteria (NTM) was investigated. No association was found between NTM presence (in oronasal swab cultures) and positive cytokine assay results. As a proof-of-principle, serial testing was applied to high-value buffaloes (n=153) in a historically bTB-free herd. Buffaloes positive on a single test (n=28) were regarded as test negative. Four buffaloes were positive on IGRA and IPRA, and M. bovis infection was confirmed following culling. These results demonstrate the value of using IGRA and IPRA in series to screen buffalo herds with no previous history of M. bovis infection.

Fitting parameters on spline curves produces more parsimonious models, maintaining fit quality. Smoothing the splines reduces predictive variance. Individual splines are often fit by type of variable, e.g., in age-period-cohort models. Linear and cubic splines are most common. Several smoothing criteria have been used for parameter curves, with cubic splines fit by constraining the integral of splines’ squared-second derivatives popular recently. Constraining the sum of squared second differences for linear splines is analogous. Generally the degree of smoothing is selected using cross-validation. Known spline dummy-variable matrices allow regression estimation of splines, with smoothing done via constrained regression. Smoothing criteria based on sums of squares or absolute values of parameters, as in ridge regression or LASSO, improves predictive accuracy and produces splines similar to smoothing by second-derivative constraints. Variables with very low t-statistics represent points where curve-shapes barely change. Eliminating those variables leaves knots concentrated where spline shapes change. A Bayesian version of this puts shrinkage priors on spline parameters. This yields realistic joint parameter distributions, avoids problems associated with using cross-validation for parameter estimation, and readily expands to non-linear modeling, such as interactions among variable types. Regularized regression and Bayesian spline methods are compared for two example datasets.

Abstract Bacteria and fungi are both used in biological seed treatments. While all have potential uses, some organisms are more widely and successfully used than others. Shelf life is an important consideration. For this reason, organisms that lack cell walls are more difficult to use than ones with long-lasting spores. Bacillus and Trichoderma are both widely effective, have good shelf life, and are frequently used. However, Rhizobiacae lack cell walls, which is a limitation; they are widely used because their symbiosis with legumes facilitates nitrogen fixation which is an important factor that provides economic, agricultural and environmental sustainability. For all organisms, proper formulation is critical for success; this is especially true for Rhizobiacae and other gram-negative bacteria. There are several specialized processes to deliver microbial agents or to enhance their biological activity, such as solid matrix priming and hydroseeding. Biorational chemicals derived from microorganisms are also frequently used. Both living organisms and biorationals provide benefits to plant agriculture. They can control diseases and increase resistance to abiotic stresses such as drought, temperature, salt, and flooding. They also can enhance mineral nutrition and photosynthesis. For these applications, the most effective ones colonize roots internally and provide season-long benefits. These endophytes induce systemic changes in plants’ gene expression and encoding of proteins.

Risk management strategies protect the company as a whole as well as employees from unforeseen financial impacts. As in the case of personal finance, preparing for certain scenarios helps to face any difficulties that the company may encounter and allows it to get out of this impasse.For any project to be successful, the way the project executing agency will deal with potential risks must be determined so that it can identify, mitigate or avoid problems when it needs to do so. Successful project managers realize that risk management is important, because the achievement of project objectives depends on planning, preparation, results and evaluation that contribute to the achievement of strategic goals, especially the sustainable development of societies.Risk management strategies work to protect the company as a whole as well as employees from unexpected financial effects, and as is the case in personal finance, preparing for certain scenarios helps to face any difficulties that the company may face and allows it to get out of this impasse.To ensure the success of your project, determine how you will handle potential risks so that you can identify, mitigate or avoid problems when you need to do so. Successful project managers understand that risk management is important, because the achievement of project objectives depends on planning, preparation, results, and evaluation that contribute to the achievement of strategic objectives.

Two welcome extensions of evolutionary thinking have come to prominence over the last thirty years: the so-called “extended evolutionary synthesis” (EES) and debate about biological kinds and individuals. These two agendas have, however, remained orthogonal to one another. The EES has mostly restricted itself to widening the explanations of adaptation offered by the preceding “modern evolutionary synthesis” by including additional mechanisms of inheritance and variation; while discussion of biological kinds has turned toward philosophical questions of essential vs. contingent properties of life forms and realist vs. epistemological approaches to categorization and classification. Here we attempt to broaden the explanatory scope of evolutionary theory by linking these two agendas. We expand on the mechanistic orientation of the EES, using new understandings of networked systems of components in order to engage the distinct intellectual challenge of the origination of historical kinds. With this phrase we designate a subset of natural kinds that acquires, through evolutionary processes, a quasi-independent lineage-history. Such kinds emerge in both biology and culture, and we enlarge the limited number of historical kinds that have thus far been recognized in evolutionary biology in a series of paradigmatic exemplars, from genes and cell types to rituals and music. For each exemplar we discern specific mechanisms by which it arose and persists; comparing these, we suggest a general unity in the ways in which diverse historical kinds originate.

Since its inception, evolutionary theory has experienced a number of extensions. The most important of these took the forms of the Modern Evolutionary Synthesis (MES), embracing genetics and population biology in the early 20^th century, and the Extended Evolutionary Synthesis (EES) of the last thirty years, embracing, among other factors, non-genetic forms of inheritance. While we appreciate the motivation for this recent extension, we argue that it does not go far enough, since it restricts itself to widening explanations of adaptation by adding mechanisms of inheritance and variation. A more thoroughgoing extension is needed, one that widens the explanatory scope of evolutionary theory. In addition to adaptation and its various mechanisms, evolutionary theory must recognize as a distinct intellectual challenge the origin of what we call “historical kinds.” Under historical kinds we include any process that acquires a quasi-independent and traceable lineage-history in biological and cultural evolution. We develop the notion of a historical kind in a series of paradigmatic exemplars, from genes and homologues to rituals and music, and we propose a preliminary characterization.

It has been known for nearly over 150 years that fatigue life data exhibits a considerable amount of variability. Furthermore, statistically modeling fatigue life adequately is challenging. Different empirical approaches have been used, each of which has merit; however, none is appropriate universally. Even when a sufficiently robust database exists, the scatter in the fatigue lives may be extremely large and difficult to characterize. The complications in empirical modeling are exacerbated for long life estimation when experimental observations are rare. The purpose of this work is to review traditional and more modern empirically based methodologies for estimating the cumulative distribution functions for fatigue life, given an applied load. To assess the applicability of the methods confidence bounds will be estimated. The analyses will be performed on an historic set of data for annealed aluminum wire tested in reverse torsion fatigue. These data are available in publications. It is recommended that a time dependent distribution function that is an based on principles of reliability that can be generalized for a variety of modeling applications should be considered for fatigue life estimation.

Since certain Mycobacterium tuberculosis complex (MTBC) members, like M. bovis, are endemic in specific South African wildlife reserves and zoos, cases of clinically important nontuberculous mycobacteria (NTM) in wildlife may be neglected. Additionally, due to the inability of tests to differentiate between host responses to MTBC and NTM, the diagnosis of MTBC may be confounded by the presence of NTMs. This may hinder control efforts. These constraints highlight the need for enhanced rapid detection and differentiation methods for MTBC and NTM, especially in high MTBC burden areas. We evaluated the use of the GeneXpert MTB/RIF Ultra, the Hain CMdirect V1.0, and novel amplicon sequencing PCRs targeting the mycobacterial rpoB and ku gene targets, directly on antemortem respiratory samples from known MTBC-infected and NTM culture-positive African elephants (n=26 animals) and rhinoceros (n=23 animals). Our findings suggest that the Ultra is the most sensitive diagnostic test for MTBC DNA detection directly in raw antemortem respiratory specimens and that the rpoB PCR is ideal for Mycobacterium genus DNA detection and species identification through amplicon sequencing.

Carcinogenesis is the process whereby a normal cell is transformed into a neoplastic cell. This action involves several steps starting with initiation and followed by promotion and progression. Driving these stages are oxidative stress and inflammation, which in turn encompasses a myriad of aberrant gene expressions, both within the transforming cell population and the cells within the surrounding lesion. Chemoprevention of cancer with bioreactive foods or their extracted/purified components occurs via normalizing these inappropriate gene activities. Various foods/agents have been shown to affect different gene expressions. In this review we discuss whereby the chemoprevention activities of the red beetroot itself may disrupt carcinogenesis and the activities of the water soluble betalains extracted from the plant.

Diagnosis of bovine tuberculosis (bTB) may be confounded by immunological cross-reactivity to Mycobacterium bovis antigens when animals are sensitised by certain nontuberculous mycobacteria (NTMs). Therefore, this study aimed to investigate NTM species diversity in African buffalo (Syncerus caffer) respiratory secretions and tissue samples, using a combination of novel molecular tools. Oronasal swabs were collected opportunistically from 120 immobilised buffaloes in historically bTB-free herds. In addition, bronchoalveolar lavage fluid (BALF; n=10) and tissue samples (n=19) were obtained during post-mortem examination. Mycobacterial species were identified directly from oronasal swab samples using the Xpert MTB/RIF Ultra qPCR (14/120 positive) and GenoType CMdirect (104/120 positive). In addition, all samples underwent mycobacterial culture, and PCRs targeting hsp65 and rpoB were performed. Overall, 55 NTM species were identified in 36 mycobacterial culture-positive swab samples with presence of esat-6 or cfp-10 detected in 20 of 36 isolates. The predominant species were M. avium complex and M. komanii. Nontuberculous mycobacteria were also isolated from 6 of 10 culture-positive BALF and 4 of 19 culture-positive tissue samples. Our findings demonstrate that there is a high diversity of NTMs present in buffaloes, and further investigation should determine their role in confounding bTB diagnosis in this species.

A survey of the trends in metal-ligand coordination and hydrogen bonding has been carried out on complexes of singly deprotonated cyanuric acid CY− and alkaline earth metals, synthesised from aqueous solution and characterised by X-ray crystallography. Involvement of cyanurate in the metal coordination increases from Mg through Ca and Sr to Ba relative to coordination by water, in parallel with the increasing ionic radius and coordination number. The incidence of bridging of metal centres by both water and cyanurate also increases in this series. The Mg complex contains hexaaqua-coordinated cations, uncoordinated CY− anions, and additional water molecules. Ca and Sr complexes feature polymeric chains of coordinated metal ions, the Ca complex with uncoordinated anions and the Sr complex with all potential ligands coordinated. The Ba complex has a two-dimensional coordination network. Extensive hydrogen bonding plays a key role in generating a three-dimensional network in all four structures. The competition between cyanurate and water for coordination to the alkaline earth metal cations, and that between coordination and hydrogen bonding propensities of the cyanurate anion, appear to be finely balanced, with the structural outcomes depending on the relative sizes and degrees of hardness of the four cations of the group.

Intercellular adhesion molecule 1 (ICAM-1/CD54), a transmembrane glycoprotein, has been considered as one of the most important adhesion molecules during leukocyte recruitment. It is encoded by the ICAM1 gene and plays a central role in inflammation. It’s crucial role in many inflammatory diseases such as ulcerative colitis and rheumatoid arthritis are well established. Given that neuroinflammation, underscored by microglial activation, is a key element in neurodegenerative diseases such as Parkinson’s disease (PD), we investigated whether ICAM-1 has a role in this progressive neurological condition and if so, elucidate the underpinning mechanisms. Specifically, we were interested in potential interaction between ICAM-1, glial cells and ferroptosis, an iron-dependent form of cell death that has recently been implicated in PD. We conclude that there exist direct and indirect (via glial cells and T cells) influences of ICAM-1 on ferroptosis and that further elucidation of these interactions can suggest novel intervention for this devastating disease.

We present a new theory to explain the expansion of the universe that augments general relativity to create a container within which quantum effects can be explained by treating time as an artefact of a fourth spatial dimension. The theory is tested by accurately modelling against stellar luminosity data that is available for redshifts, z

Interactions between human immunodeficiency virus type 1 (HIV-1) and the host factors or restriction factors of its target cells determine the cell’s susceptibility to, and outcome of, infection. Factors intrinsic to the cell are involved at every step of HIV-1’s replication cycle, contributing to productive infection and replication, or severely attenuating HIV-1’s chances of success. Furthermore, factors unique to certain cell types contribute to the differences in infection between these cell types. Understanding the involvement of these factors in HIV-1 infection is a key requirement for the development of anti-HIV-1 therapies. As the list of factors grows, and the dynamic interactions between these factors and the virus are elucidated, comprehensive and up-to-date summaries that recount the knowledge gathered after decades of research are beneficial to the field, displaying what is known so that researchers can build off the groundwork of others to investigate what is unknown. Herein, we aim to provide a review focusing on protein host factors, both well-known and relatively new, that impact HIV-1 replication in a positive or negative manner at each stage of the replication cycle, highlighting factors unique to HIV-1’s various target cell types where appropriate.

Viral tropism is most commonly linked to receptor use, but host cell protease use can be a notable factor in susceptibility to infection. Here we review the use of host cell proteases by human viruses, focusing on those with primarily respiratory tropism, particularly SARS-CoV-2. We first describe the various classes of proteases present in the respiratory tract, as well as elsewhere in the body, and incorporate the targeting of these proteases as therapeutic drugs for use in humans. Host cell proteases are also linked to the systemic spread of viruses and play important roles outside of the respiratory tract; therefore, we address how proteases affect viruses across the spectrum of infections that can occur in humans, intending to understand the extrapulmonary spread of SARS-CoV-2.

Ostreid herpesvirus 1 (OsHV-1) is one of the most economically important pathogens of Pacific oysters. Understanding the pathogenesis of this virus is critical to developing tools to control outbreaks on shellfish farms. OsHV-1 is genetically related to vertebrate herpesviruses, which have a lytic and a latent stage, with the latent stage capable of being reactivated to the lytic stage. Here, OsHV-1 latency in Pacific oysters was investigated in experimentally and naturally infected oysters. Lytic infection in one-year-old oysters injected with the Tomales Bay strain of OsHV-1 was detectable between 1 and 4 days post-infection (dpi) but was not detectable after 5 dpi. The infected oysters shed 1102 to 1104 DNA copies/ml during the 4-day acute phase. At 21 dpi, the recovered oysters were temperature and chemically stressed and were found to shed 1104 to 1105 DNA copies/ml over a period of 48 h. Lytic shedding was not detectable in two-year-old oysters injected similarly with the same strain of OsHV-1; however, the OsHV-1 genome was detectable by qPCR in the adductor muscle, gill, mantle, and hemocytes within the first 3 dpi, after which it became undetectable. No OsHV-1 was detectable in the adductor muscle, gill, or mantle from experimentally infected oysters on days 15 and 21 post-infection or from oysters sampled 9 months after surviving an OsHV-1 mortality event; however, OsHV-1 DNA could be detected in hemocytes of both experimentally infected oysters at 21 dpi and naturally infected oysters. In addition, lytic viral gene transcription was detectable in hemocytes of experimentally infected oysters between 1 and 21 dpi and in hemocytes of naturally infected oysters.

Intermolecular interactions are the fabrics underlying almost all processes in living organisms, where two cornerstone concepts, intermolecular binding affinity (K d ) and binding energy (ΔG), have long been established to physically describe the strengths of biomolecular interactions, e.g., drug-target K d and ΔG to describe the strength of drug-target interaction. The past two-three years saw a big step forward in the use of artificial intelligence (AI) in structural biology (e.g., AlphaFold for protein structure prediction) and drug discovery & design. In light of the roles of K d and ΔG in drug discovery & design, the speed of this AI progress raises a question of what’s next for its practical application in the pharmaceutical industry, in addition to a system-wide account of biomolecular structures and motions. Last August, the concept of a general intermolecular binding affinity calculator (GIBAC) was for the first time coined and proposed in an MDPI-published preprint. Here, this article puts forward an updated conceptual and practical framework of GIBAC, including its inception, definition, construction, practical applications, technical challenges and limitations, and future directions. Moreover, this article argues that the time is now ripe for the construction of such an accurate, precise and efficient GIBAC to be on the agenda of the entire drug discovery & design community, to ensure its applicability & reliability, and to enhance its value in drug R&D in future.

Primates have an unparalleled ability to produce a wide range of dexterous movements, each sensitive to context and robust to perturbation. Recent progress in understanding the neural basis of movement generation comes from two largely independent ideas, “Optimal Feedback Control” and “Neural Dynamical Systems”. The optimal control framework was largely inspired by research programs from the ‘80s showing that the brain doesn’t seem to plan a simple desired movement trajectory, but instead produces movements by transforming sensory information into motor output that satisfies an optimality criterion. The more recent idea that the motor cortex acts as a dynamical system came about only as it became possible to analyze large numbers of simultaneously recorded single neurons. These two framings of the motor system have been largely incommensurate, neither able to contribute much to the understanding of the other. In this review, we reconcile these two views into a single model we call “Dynamical Feedback Control”. We propose that the dynamics in the motor cortex emerge from a sensorimotor transformation that couples the motor cortex to sensory input from the periphery, and to contextual inputs from other cortical and subcortical areas. Dynamics in motor cortex can be thought to approximate gains of a feedback controller, and by moving the neural state to different regions of state space, the motor system can rapidly alternate between different controllers. The DFC framework presents a new lens to interpret neural dynamics, and to understand how ensembles of neurons generate flexible and responsive patterns of muscle activity.

Recently, coastal swamps have been acknowledged for their capability to alleviate shorelines and defend coastal communities. Mangroves play a prominent role in obstructing water currents in riverbanks, shorelines, and coastal areas. Mangrove roots have the significant contribution to the resiliency of the vegetation structure. Yet, mangrove model has lately been called into question by lab experimental evidence. In this paper, the flow characteristics past root models are reviewed. coastal swamps are among the most fruitful and carbon‐rich ecosystems on the planet. Long‐term carbon putting away in coastal wetlands happens mostly below ground as soil organic matter. Mangrove servs as a carbon sink, impacts wetland ecosystem configuration, purpose, and firmness. To expect and ease the properties of climate change, there is a necessity to advance considerate of environmental controls on wetland. The impact of four soil formation factors are reviewed. Across the shorelines, soil organic matter was highest in mangrove forests and it was lower areas.

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

Current treatments for medial meniscus lesions in association with CCL ruptures [1–5] have shown disappointing long-term outcomes [6]. Meniscal suturing may improve the outcome, but their clinical application remains limited [7–9]. This study aims to assess the practicability of a minimally invasive DNT to facilitate meniscal suturing in dogs. Ten stifles of eight client-owned dogs with arthroscopically confirmed CCL disease and medial meniscal tears in the abaxial third of the meniscus were included. The described suture technique was applied under joint distraction using the Titan joint distractor.[8] Surgical stabilization of all stifles was then accomplished through a X-Porous TTA procedure [10]. The DNT allowed for the precise placement of meniscal sutures. Minor intraoperative complications included reduced arthroscopic visibility (n=2) and suture breakage during its passage through the meniscus (n=3). No complications related to the meniscal sutures were noted throughout the six-month follow-up. The described DNT proved to be a viable and effective method for suturing lesions of the caudal horn of the medial meniscus, provided there is adequate visualization during the procedure. Appropriate stifle stabilization postoperatively is mandatory for protecting the suture and avoiding concomitant meniscal lesions due to joint instability.

Xenorhabdus nematophila and Photorhabdus luminescens are entomopathogenic symbionts that produce several toxic proteins that can interfere with the immune system of insects. Here, we showed that outer membrane proteins (OMPs) could be involved as virulence factors during bacterial symbiont pathogenesis. Purified OMPs from bacterial culture were injected fifth instar larvae of Spodoptera exigua Hübner. Larvae were surveyed for fluctuations in total haemocyte counts (THC), granulocyte percentage (cellular defence), protease, phospholipase A2 (PLA₂), and phenoloxidase (PO) activities (humoral defence) at specific time intervals. Changes in the expression of the three antimicrobial peptides (AMPs), cecropin, attacin, and spodoptericin, were also measured. Larvae treated with both types of OMPs had more haemocytes than did the negative controls. OMPs of X. nematophila caused more haemocyte destruction than did the OMPs of P. luminescens. The OMPs of both bacterial species initially activated insect defensive enzymes post-injection, their activating fluctuated in different ways. Attacin, cecropin and spodoptericin were up-regulated by OMP injections more than in normal larvae. The expression of these three AMPs was maximal at four hpi with P. luminescens OMPs treatment. Expression of the three AMPs in X. nematophila treatment was irregular and lower than in the P. luminescens OMPs treatment. These findings provide insights into the role of OMPs of entomopathogenic nematode bacterial symbionts in countering the physiological defenses of insects.

Localizing the source of a signal is often as important as deciphering the signal’s message. Localization mechanisms must cope with the challenges of representing the spatial information of weak, noisy signals. Comparing these strategies across modalities and model systems allows a broader understanding of the general principles shaping spatial processing. In this review we focus on the electrosensory system of knifefish and provide an overview of our current understanding of spatial processing in this system, in particular, localization of conspecific signals. We argue that many mechanisms observed in other sensory systems, such as the visual or auditory systems, have comparable implementations in the electrosensory system. Our review therefore describes a field of research with unique opportunities to provide new insights into the principles underlying spatial processing.

A new process is reported for the incorporation of a fluoropolymer into a solid perovskite film. Poly(trifluoroethyl methacrylate) [CH2C(CH3)(CO2CH2CF3)]n was delivered to methylammonium lead iodide (CH3NH3PbI3) perovskite films by crystallizing the film in supercritical carbon dioxide/ethanol containing the dissolved fluoropolymer. The surface was characterized before and after fluoropolymer exposure using scanning electron microscopy, Raman spectroscopy and contact angle measurements. The results indicate that the fluoropolymer was incorporated into the perovskite film during the supercritical fluid crystallization process.

The coronavirus disease 2019 (COVID-19) pandemic, caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has spread rapidly to most parts of the world, causing high numbers of deaths and significant social and economic impacts. SARS-CoV-2 is a novel coronavirus with a suggested zoonotic origin and with the potential for cross-species transmission among animals. Antarctica can be considered the only continent free of SARS-CoV-2 although at the end of the 2019-2020 tourist season, at least one SARS-CoV-2 positive tourist visited the Antarctic Peninsula. Therefore, concerns have been expressed regarding the potential human introduction of this virus to the continent through the activities of research or tourism with potential effects including those related to human health, but also the potential for virus transmission to Antarctic wildlife. This reverse-zoonotic transmission risk to Antarctic wildlife is assessed considering the available information on host susceptibility, dynamics of the infection in humans, and contact interactions between humans and Antarctic wildlife. Measures to reduce the risk are proposed as well as the identification of knowledge gaps related to this issue.

Reassessment of the fatigue life for wind turbines structural components is typically performed using deterministic methods with the same partial safety factors as used for the original design. However, in relation to life extension, the conditions are generally different from the assumptions used for calibration of partial safety factors; and using a deterministic assessment method with these partial safety factors might not lead to optimal decisions. In this paper, the deterministic assessment method is compared to probabilistic and risk-based approaches, and the economic feasibility is assessed for a case wind farm. Using the models also used for calibration of partial safety factors in IEC61400-1 ed. 4 it is found that the probabilistic assessment generally leads to longer additional fatigue life than the deterministic assessment method. The longer duration of the extended life can make life extension feasible in more situations. The risk-based model is applied to include the risk of failure directly in the economic feasibility assessment and it is found that the reliability can be much lower than the target for new turbines, without compromising the economic feasibility.

Pathologic angiogenesis is responsible for much of the vision loss that stems from several chorioretinal vascular diseases including neovascular age-related macular degeneration (nAMD), diabetic retinopathy (DR), and retinal vein occlusion (RVO). Because vascular endothelial growth factor (VEGF) serves as a pivotal angiogenic molecule, it has emerged as the primary target for therapeutic drugs. Current anti-VEGF therapy is dominated by bevacizumab, ranibizumab, and aflibercept, all of which have been available for more than a decade, but new drugs, both biosimilars (Byooviz and Cimerli) and drugs whose primary aim is to decrease treatment burden (brolucizumab, faricimab, and the ranibizumab port delivery system), have been approved. Recent failures (conbercept, abicipar, and KSI-301) emphasize the complexity of drug development and the difficulties faced by innovators. Most therapies under development, including tyrosine kinase inhibitors and gene therapy, include VEGF-A blockade as their primary function and aim to extend durability rather than increase peak efficacy. But even as many new drugs look to extend durability, cost containment with mandated use of biosimilars serves to balance the therapeutic landscape.

Evaluating new, promising organic molecules to make next-generation organic optoelectronic devices necessitates the evaluation of charge carrier transport performance through the semi-conducting medium. In this work, we utilize quantum chemical calculations (QCC) and kinetic Monte Carlo (KMC) simulations to predict the zero-field hole mobilities of ~100 morphologies of the benchmark polymer poly(3-hexylthiophene), with varying simulation volume, structural order, and chain-length polydispersity. Morphologies with monodisperse chains were generated previously using an optimized molecular dynamics force-field and represent a spectrum of nanostructured order. We discover that a combined consideration of backbone clustering and system-wide disorder arising from side-chain conformations are correlated with hole mobility. Furthermore, we show that strongly interconnected thiophene backbones are required for efficient charge transport. This definitively shows the role "tie-chains" play in enabling mobile charges in P3HT. By marrying QCC and KMC over multiple length- and time-scales, we demonstrate that it is now possible to routinely probe the relationship between molecular nanostructure and device performance.

In this paper, we examine the mathematical and physical consistencies of the three primary couple stress theories: original Mindlin-Tiersten-Koiter couple stress theory (MTK-CST), modified couple stress theory (M-CST) and consistent couple stress theory (C-CST). As has been known for many years, MTK-CST suffers from some fundamental inconsistencies, such as the indeterminacy of the couple-stress tensor. Therefore, despite the fact that MTK-CST has a fundamental position in the evolution of size-dependent continuum mechanics, it is not a reliable theory within continuum mechanics, for example, in developing new size-dependent multi-physics formulations. We also observe that M-CST not only inherits all inconsistences from the original MTK-CST, but also suffers from new additional inconsistencies, such as the introduction of a new non-physical governing equation. These inconsistencies refute the claim of those who state that the couple-stress tensor may be chosen symmetric. Therefore, the apparent success of MTK-CST and M-CST in describing a size-effect for some problems, such as two-dimensional plate and beam bending, is not enough to justify these theories as suitable for general cases. In fact, the symmetric couple-stresses in M-CST create torsional or anticlastic deformation, not bending. On the other hand, C-CST, with a skew-symmetric couple-stress tensor, is the consistent continuum mechanics suitable for solving different size-dependent solid, fluid and multi-physics problems.

Retinoic acid receptor-related orphan receptor γ (RORγ) is a transcription factor regulating the expression of the pro-inflammatory cytokine IL-17 in human T helper 17 (Th17) cells. Activating RORγ can induce multiple IL-17-mediated autoimmune diseases but may also be useful for anticancer therapy. Its deep immunological functions make RORɣ an attractive drug target. Over 100 crystal structures have been published describing atomic interactions between RORɣ and agonists and inverse agonists. In this review, we focus on the role of dynamic properties and plasticity of the RORɣ orthosteric and allosteric binding sites by examining structural information from crystal structures and simulated models. We discuss the possible influences of allosteric ligands on the orthosteric binding site. We find that high structural plasticity favors the druggability of RORɣ, especially for allosteric ligands.

Distant Retrograde Orbits in the Earth-Moon system are gaining in popularity as stable `parking' orbits for various conceptual missions. To investigate the stability of potential Distant Retrograde Orbits, simulations were executed, with propagation running over a thirty-year period. Initial conditions for the vehicle state were limited such that the position and velocity vectors were in the Earth-Moon orbital plane, with the velocity oriented such that it would produce retrograde motion about Moon. The resulting trajectories were investigated for stability against the eccentric relative orbits of Earth and Moon in an environment that also included gravitational perturbations from Sun, Jupiter, and Venus, and the effects of radiation pressure. The results appear to indicate that stability is enhanced for certain resonant states within the Earth-Moon system.

A systematic study has been conducted on barbiturate complexes of all five alkali metals Li–Cs prepared from the metal carbonates or hydroxide in aqueous solution without other potential ligands present, varying the stoichiometric ratio of metal ion to barbituric acid (BAH). Eight polymeric compounds (two each for Na, K, and Rb and one each for Li and Cs) have been characterised by single-crystal X-ray diffraction. All contain some combination of barbiturate anion BA− (necessarily in a 1:1 ratio with the metal cation M+), barbituric acid, and water. All organic species and water molecules are coordinated to the metal centres via oxygen atoms as either terminal or bridging ligands. Coordination numbers range from 4 (for the Li complex) to 8 (for the Cs complex). Extensive hydrogen bonding plays a significant role in all the crystal structures, almost all of which include pairs of N–H…O hydrogen bonds linking BA− and/or BAH components into ribbons extending in one dimension. Factors influencing the structure adopted by each compound include cation size and reaction stoichiometry as well as hydrogen bonding.

The nucleation and dynamics of Josephson and Abrikosov vortices determine the critical currents of layered high-T_c superconducting (HTS) thin films, grain boundaries, and coated conductors, so understanding their mechanisms is of crucial importance. Here we treat pair creation of Josephson and Abrikosov vortices in layered superconductors as a secondary Josephson effect, in which each full vortex is viewed as a composite fluid of micro-vortices, such as pancake vortices, which tunnel coherently via a tunneling matrix element. We introduce a two-terminal magnetic (Weber) blockade effect that blocks tunneling below a threshold current, and simulate time-correlated vortex tunneling above threshold. The model shows nearly precise agreement with voltage-current (V-I) characteristics of HTS cuprate grain boundary junctions, which becomes more concave rounded as temperature decreases, and also explains the piecewise linear V-I behavior observed in iron-pnictide bicrystal junctions and other HTS devices. When applied to either Abrikosov or Josephson pair creation, the model explains a plateau seen in plots of critical current vs. thickness of HTS coated conductors. The observed correlation between theory and experiment strongly supports the proposed quantum picture of vortex nucleation and dynamics in layered superconductors.

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

Quaking aspen (Populus tremuloides Michx.) landscapes are valued for their biodiversity, water retention, fire mitigation, aesthetics, and recreation opportunities. Across North America, some aspen populations are experiencing population declines as they face uninhibited ungulate browsing, drought, fire suppression, insects, disease, and inappropriate management. Increased human development and recreational use within aspen landscapes can serve as additive stressors, though there is a dearth of literature examining these elements. At a popular recreational area in Utah, USA, identifying the cause of apparent decline within a larger aspen community is complicated by development upstream and recreation-related activities. We sought to: 1) assess the overall condition of the aspen at the site, 2) understand key variables that influence aspen conditions, and 3) elucidate how aspen fitness varies across the site. We collected data from forty-five plots using established aspen sampling methods, including ungulate presence, tree characteristics, soil chemistry, and environmental descriptors. Results suggest that a combination of higher levels of browsing and elevated soil sodium may be causing premature mortality and limiting aspen recruitment in a portion of the study area. These findings will inform future management at this site, as well as similar recreational forest settings experiencing compound stressors.

Sweetness drives consumption of added sugars, so understanding how individuals differ is important for developing strategies to lower sugar intake. However, methods to assess hedonic response to sweetness vary, making results across studies difficult to integrate. We compared methods to measure optimal sucrose concentration in 21 healthy adults (1) using paired-comparison preference tracking vs. ratings of liking, (2) with participants in the laboratory vs. at home, and (3) using aqueous solutions vs. vanilla milk. Tests were replicated on separate days to assess test-retest reliability. Test-retest reliability was similar between laboratory and home testing, but tended to be better for vanilla milk and preference tracking. Optimal sucrose concentration was virtually identical between laboratory and home, slightly lower when estimated via preference tracking, and about 50% lower in vanilla milk. However, individual optimal sucrose concentration correlated strongly between Methods, test Locations, and Stimuli. More than 50% of the variability in optimal sucrose concentration could be attributed to consistent differences among individuals while much less variability was attributable to differences in Methods, test Locations or Stimuli. These results demonstrate convergent validity between measures of preference and liking, support testing at home to lower participant burden, and suggest that aqueous solutions can be useful proxies for some commonly consumed beverages for measuring individual differences.

The development of autonomous vehicles is becoming increasingly popular and gathering real world data is considered a valuable task. Many datasets have been published recently in the autonomous vehicle sector, with synthetic datasets gaining particular interest due to availability and cost. For a real implementation and correct evaluation of vehicles at higher levels of autonomy it is also necessary to consider human interaction, which is precisely something that lacks in existing datasets. In this article the UPCT dataset is presented, a public dataset containing high quality, multimodal data obtained using state of the art sensors and equipment installed onboard the UPCT’s CICar autonomous vehicle. The dataset includes data from a variety of perception sensors including 3D LiDAR, cameras, IMU, GPS, encoders, as well as driver biometric data and driver behaviour questionnaires. In addition to the dataset, the software developed for data synchronisation and processing has been made available. The quality of the dataset was validated using an end-to-end neural network model with multiple inputs to obtain speed and steering wheel angle and obtained very promising results.

Oxalate, a compound produced by many edible plants and as a terminal metabolite in the liver of mammals, is a toxin that has a detrimental role to human health. Humans and other mam-mals do produce the enzymatic machinery to degrade oxalate. However, numerous oxa-late-degrading bacteria reside in the mammalian gut and thus provide an important function for hosts. The current review focuses on the environmental factors that influence the efficacy of pro-biotic oxalate-degrading bacteria, relative to oxalate metabolism. We describe the mechanism of oxalate catabolism and its consumption by obligate and facultative anaerobic oxalate-degrading bacteria, in both in vitro and in vivo environments. We also explore the environmental variables that impact oxalate degradation. Studies on single species degrade oxalate have not shown a strong impact on oxalate metabolism especially in high oxalate conditions such as consumption of foods high in oxalate (such as coffee and chocolate for humans or halogeton in animal feed). Considering effective variables which enhance oxalate degradation could be used in application of effective probiotic as a therapeutic tool in individuals with hyperoxaluria. This study indicates probiotics can be considered a good source of naturally occurring oxalate degrading agent in human colon

Indocyanine Green (ICG) has significantly advanced minimally invasive surgery. It is widely recognized for its ability to visualize blood vessel patency in real-time across various surgical specialties. While its primary use in colorectal surgery is to evaluate anastomoses for leaks, nu-merous other applications have been documented in the literature. In this review, we aim to explore both established and emerging applications of ICG fluorescence in colorectal surgery, with the goal of improving patient outcomes. This includes preoperative tumor marking and the detection of metastatic disease. Some applications, such as lymphatic mapping, require further research to determine their impact on clinical practices. Conversely, oth-ers, like the intraoperative localizations of ureters, necessitate additional procedures and are not yet widely accepted by the surgical community. However, the development of alternative com-pounds could offer better solutions. Future research should focus on areas like quantitative ICG and protocol standardization in prospective multicenter studies.

The purpose of this study was to elucidate patterns and mechanisms driving seasonal and inter-annual variations of carbon and nitrogen stable isotopes in the zooplankton crustacean commu-nity of Lake Maggiore (Italy), during the period 2009-2020. Different zooplankton taxa and groups revealed different ranges of d13C signatures, giving an insight into food sources and niche partition. In particular, cyclopoids had a restricted range with most negative d13C‰ values and increase in d13C fractionation with the establishment of water thermal vertical stratification, high-lighting the importance of vertical distribution as key factor for taxa coexistence in a vertically heterogenous environment. d13C of the zooplankton community and of Daphnia were positively related to water temperature (R2=0.58 p <0.0001 and R2=0.68 p <0.0001, respectively) and d13C Daphnia signature to chlorophyll-a (R2=0.32, p < 0.0001). Decomposition of time series data for zooplankton carbon and nitrogen signatures and environmental parameters identified increasing trends in water temperature, chlorophyll-a and water conductivity and decrease in nitrate, that matched changes in carbon isotopic signature trend in some zooplankton taxa (Bosmina, Daphnia and diaptomids). Overall, the observed patterns in zooplankton isotopic signatures were interpreted as integrations of climate warming effects in Lake Maggiore, affecting both food sources availability and environmental conditions.

Recently a new class of experiments in the field of surface gravity waves has emerged. These experiments serve as demonstration of an analogy to a broad variety of phenomena in optics and quantum mechanics. In particular, experiments involving Airy water-wave packets were carried out. The Airy wave packets have attracted tremendous attention in optics and quantum mechanics owing to their unique properties, spanning from an ability to propagate along parabolic trajectories without spreading, and to accumulating a phase that scales with the cubic power of time. Non-dispersive Cosine-Gauss wave packets and self-similar Hermite-Gauss wave packets, also well known in the field of optics and quantum mechanics, were recently studied using surface gravity waves as well. These wave packets demonstrated self-healing properties in water wave pulses as well, preserving their width despite being dispersive. Finally, this new approach also allows to observe diffractive focusing from a temporal slit with finite width.

This paper describes the feasibility and probable benefits associated with greening the Tahliah Channel, a concrete drainage channel that was originally built to relieve urban flooding in Jeddah City, Saudi Arabia. It includes an estimation of irrigation needs for channel greening based on a standardized planting specification. The study also demonstrates alternative strategies for meeting the required irrigation demand, including water harvesting and graywater reuse on a residential scale. The study shows that greening Tahliah Channel is possible relying mainly on graywater reuse from the surrounding buildings. Also, the study shows that rainwater harvesting is not a reliable source for irrigation. Rather, it can cover only part of the irrigation needs (6%) and so can be used as a secondary supporting source. The positive results of this case study will be of interest to those in arid countries who are looking to upgrade and replace traditional, single function drainage infrastructure with more sustainable, green infrastructure systems. More specifically, the objectives of the study are consistent with the goals of the Saudi government’s ongoing initiative that advocates for more resilient and sustainable cities. (Vision 2030 year).

Given their severity and non-healing nature, diabetic chronic wounds are a significant concern to the 30.3 million Americans diagnosed with diabetes mellitus (2015). Peripheral arterial diseases, neuropathy, and infection contribute to the development of these wounds, which lead to an increased incidence of lower extremity amputations. Early recognition, debridement, offloading, and controlling infection are imperative for timely treatment. However, wound characterization and treatment are highly subjective and based largely on the experience of the treating clinician. Many wound dressings have been designed to address particular clinical presentations, but a prescriptive method is lacking for identifying the particular state of chronic, non-healing wounds. The authors suggest that recent developments in wound dressings and biosensing may allow for the quantitative, real-time representation of the wound environment, including exudate levels, pathogen concentrations, and tissue regeneration. Development of such sensing capability could enable more strategic, personalized care at the onset of ulceration and limit the infection leading to amputation. This review presents an overview of the pathophysiology of diabetic chronic wounds, a brief summary of biomaterial wound dressing treatment options, and biosensor development for biomarker sensing in the wound environment.

Breastmilk is the only recommended source of nutrition for infants below six-months of age. However, a significant proportion of children are either on supplemental breastfeeding(SBF) or weaned due to the early introduction of solid/semi-solid/soft food and liquids(SSF) before 6 months of age. There is good evidence that Exclusive Breastfeeding(EBF) in infants below six-months of age protects them from preventable illnesses, including malnutrition. The relationship between infant feeding practices and coexisting forms of malnutrition(CFM) has not yet been explored. This study examined the association of different feeding indicators(continuation of breastfeeding, predominant feeding, and SSF) and feeding practices(EBF, SBF, and complete weaning) with CFM in infants aged below six-months of age in Pakistan. National and regional datasets of Pakistan from the last ten years were retrieved from the Demographic Health Surveys(DHS) and UNICEF data repositories. In Pakistan, 34.5%(n=6131) of infants have some form of malnutrition. Among malnourished infants, 44.7%(~15.4% of the total sample) had a CFM. Continuation of breastfeeding was observed in more than 85% of infants, but less than a quarter were on EBF, and the rest were either SBF(65.4%) or weaned infants(13.7%). Compared to EBF, complete weaning increased the odds of coexistence of underweight with wasting and underweight with both wasting and stunting by 1.96(1.12-3.47) and 2.25(1.16-4.36), respectively. Overall, breastfed children had lower odds of various forms of CFM (compared to non-breastfed), except for the coexistence of stunting with overweight/obesity. Continuation of any breastfeeding protects infants in Pakistan from various types of CFM during the first six months of life.

Duchenne muscular dystrophy (DMD) is caused by genetic mutations in the cytoskeletal-sarcolemmal anchor protein dystrophin. Repeated cycles of sarcolemmal tearing and repair lead to a variety of secondary cellular and physiological stressors that are thought to contribute to weakness, atrophy, and fibrosis. Collectively, these stressors can contribute to a pro-inflammatory milieu in locomotor, cardiac, and respiratory muscles. Given the many unwanted side effects that accompany current anti-inflammatory steroid-based approaches for treating DMD (e.g., glucocorticoids), there is a need to develop new therapies that address inflammation and other cellular dysfunctions. Adiponectin receptor (AdipoR) agonists, which stimulate AdipoR1 and R2 isoforms on various cell types, have emerged as therapeutic candidates for DMD due to their anti-inflammatory, anti-fibrotic, and pro-myogenic properties in pre-clinical human and rodent DMD models. Although these molecules represent a new direction for therapeutic intervention, the mechanisms through which they elicit their beneficial effects are not yet fully understood, and DMD-specific data is limited. The overarching goal of this review is to investigate how adiponectin signaling may ameliorate pathology associated with dystrophin deficiency through inflammatory-dependent and -independent mechanisms, and to determine if current data supports their future progression to clinical trials.

This study introduces and demonstrates a comprehensive, accurate, unbiased approach to robust quantitative comparison of Electronic Nicotine Delivery Systems (ENDS) appropriate for establishing substantial equivalence (or lack thereof) between tobacco products. The approach is demonstrated across a family of thirteen pen- and pod-style ENDS products. Methods employed consist of formulating a robust emissions surface regression model, quantifying the empirical accuracy of the model as applied to each product, evaluating relationships between product design characteristics and maximum emissions characteristics, and presenting results in formats useful to researchers, regulators, and consumers. Results provide a response surface to characterize emissions (total particulate matter and constituents thereof) from each ENDS appropriate for use in a computer model and for conducting quantitative exposure comparisons between products. Results demonstrate that emissions vary as a function of puff duration, flow rate, E-Liquid composition, and device operating power. Further, results indicate that regulating design characteristics of ENDS devices and consumables may not achieve desired public health outcomes; it is more effective to regulate maximum permissible emissions directly. Three emissions outcome measures (yield per puff, mass concentration and constituent mass ratio) are recommended for adoption as standard quantities for reporting by manufacturers and research laboratories. The approach provides a means of (a) quantifying and comparing maximal emissions from ENDS products spanning their entire operating envelope, (b) comparative evaluation of ENDS devices and consumable design characteristics, and (c) establishing comparative equivalence of maximal emissions from ENDS. A consumer-oriented product emissions dashboard is proposed for comparative evaluation of ENDS exposure potential. Maximum achievable power dissipated in the coil of ENDS is identified as a potentially effective regulatory parameter.

The article discusses issues related to the optimization of the operation of medium voltage networks, focusing on the optimization of network division points and the selection of the optimal network configuration aimed at reducing power and energy losses. The article provides a critical review of selected scientific works from recent years on the issue of network configuration optimization. The developed solution uses non-deterministic network models and statistical and probabilistic approaches. Optimization studies were carried out using heuristic optimization methods and proprietary algorithms for forecasting the load and power generated from renewable energy sources. The solution proposed in the article has many application possibilities. It can be used to optimize the location of network division points (reducing economic costs related to the modernization of network infrastructure) as well as to optimize the reconfiguration process in order to reduce power losses while maintaining voltage criteria.

Expression of the breast cancer resistance protein (BCRP/ ABCG2) transporter is downregulated in placentas from women with preeclampsia (PE) and in an immunological rat model of PE, which closely resembles human PE. While many drugs are substrates of this important efflux transporter, the impact of BCRP downregulation on maternal and fetal drug exposure has not been investigated. Using the PE rat model, we performed a pharmacokinetic study with rosuvastatin (RSV), a BCRP substrate, to investigate this impact. PE was induced in rats during gestational days (GD) 13 to 16 with daily low-dose endotoxin. On GD18, RSV (3 mg/kg) was administrated intravenously, and rats were sacrificed at time intervals between 0.5-6 hours. Placental expression of Bcrp and Oatp2b1 significantly decreased in PE rats. A corresponding increase in RSV levels was seen in fetal tissues and amniotic fluid of the PE group (p&lt;0.05), while maternal plasma concentrations remained unchanged. An increase in Bcrp expression and decreased RSV concentration, was seen in the livers of PE dams. This suggests that PE-mediated transporter dysregulation leads to significant changes in the maternal and fetal RSV disposition. Overall, our findings demonstrate that altered placental expression of transporters in PE can increase fetal accumulation of their substrates.

Urban tree planting initiatives can experience high levels of mortality during establishment years. Mortality tied to the stresses of transplanting can be partially negated or exacerbated depending on the species selected, nursery materials used, site conditions present, and management practices employed. Past research has quantified post-planting survival, health, and growth. However, varying climates, species, land use types, and management practices warrant additional region-specific research. The purpose of this study is to assess the success of plantings along Florida highways and identify species, site, and management factors related to tree and palm health and establishment. Results show high annual establishment survival (98.5%) across 21 planting projects ranging from 9 to 58 months after installation, (n = 2711). For transplanted palms, the presence of on-site irrigation significantly improved establishment from 96.2% to 99.4%. No establishment differences were detected with regard to irrigation treatment for small-stature trees, shade trees, and conifers. Additionally, there were significant differences in tree health response among tree groups given species, management, and site factors.

COVID-19, previously known as “2019 novel coronavirus”, is a newly discovered virus which causes severe acute respiratory syndrome, similar to corona virus 2 (SARS-CoV-2), which has spread widely through human to human contact and was declared a pandemic by the WHO in March 2020. To cope with this pandemic many countries have adopted nationwide lockdowns which restrict nonessential activities and encourage their populations to avoid public transport, work from hone wherever possible, and to maintain social distancing at all times. While the severity of these shutdowns has varied with country, large geographic regions of the world (including China, India, Iran, Italy, Spain, and the USA) have all been severely affected, not just in the loss of human life, but also in terms of the financial impacts the lockdowns will have on their countries future prosperityIt was previously reported that a number of environmental factors, including humidity and temperature, played an important role in development and spread of the SARS-Corona Virus infection with the virus retaining viability for over 5 days at temperatures between 22–25^oC and relative humidity (RH) of 40–50%. Whereas, elevated temperatures and higher RH (38^oC, and >95% RH) decreased virus viability (Kroumpouzos et al., 2020). The spread of COVID-19 started in low temperature areas of China, with major outbreaks subsequently occurring in Iran, Japan, Northern Italy and South Korea. These new virus epicenters all had similar temperature and latitude, along the 30-50^◦N” zone. Subsequently, the virus was spread to regions of elevated temperature, such as India, the Middle East and Thailand, due to international travel (Kroumpouzos et al., 2020).The aim of this study was to consider the environmental impact of COVID-19, including water pollution. The paper is divided into four sections. In the first section the current literature related to COVID-19 is reviewed. In the second section a recent update on COVID-19 globally is presented, followed by a descriptive impact on the environment in the third section and finally in the fourth section the COVID-19 related worldwide environmental impact is discussed. Since COVID-19 is a currently an active pandemic with no end in sight, while constructive conclusions can only be made on the limited data currently, which may be prone to high errors. However, these conclusions may provide some preliminary suggestions for assisting in assessing spreading patterns of COVID-19 across the globe, and may be of long-term significances with respect to assessing the environmental impact of lockdown policies due to COVID-19 worldwide.

Current dry powder formulations for inhalation deposit a large fraction of their emitted dose in the upper respiratory tract where they contribute to off-target adverse effects and variability in lung delivery. The purpose of current study is to design a new formulation concept that more effectively targets inhaled dry powders to the large and small airways. The formulations are based on adhesive mixtures of drug nanoparticles and nanoleucine carrier particles prepared by spray drying of a co-suspension of leucine and drug particles from a nonsolvent. The physicochemical and aerosol properties of the resulting formulations are presented. The formulations achieve 93% lung delivery in the Alberta Idealized Throat model that is independent of inspiratory flow rate and relative humidity. Largely eliminating URT deposition with a particle size larger than solution pMDIs is expected to improve delivery to the large and small airways, while minimizing alveolar deposition and particle exhalation.

This paper compares a series of traditional and deep learning methodologies for the segmentation of textures. Six well-known texture composites first published by Randen and Hus{\o}y were used to compare traditional segmentation techniques (co-occurrence, filtering, local binary patterns, watershed, multiresolution sub-band filtering) against a deep-learning approach based on the U-Net architecture. For the latter, the effects of depth of the network, number of epochs and different optimisation algorithms were investigated. Overall, the best results were provided by the deep-learning approach. However, the best results were distributed within the parameters, and many configurations provided results well below the traditional techniques.

A Wireless Body Area Network (WBAN) is a network of wirelessly connected sensing and actuating devices. WBANs used for recording biometric information and administering medication are classified as part of a Cyber Physical System (CPS). Preserving user security and privacy is a fundamental concern of WBANs, which introduces the notion of using biometric readings as a mechanism for authentication. Extensive research has been conducted regarding the various methodologies (e.g. ECG, EEG, gait, head/arm motion, skin impedance). This paper seeks to analyze and evaluate the most prominent biometric authentication techniques based on accuracy, cost, and feasibility of implementation. We suggest several authentication schemes which incorporate multiple biometric properties.

Human milk (HM) is the gold standard for feeding infants but has been associated with slower growth in preterm infants compared with preterm formula. This systematic review and meta-analysis summarises the post-1990 literature to examine the effect of HM feeding on growth during the neonatal admission of preterm infants with birth weight ≤1500g and/or born ≤28 weeks’ gestation. Medline, PubMed, CINAHL and Scopus were searched, and comparisons grouped as: exclusive human milk (EHM) vs exclusive preterm formula (EPTF), any HM vs EPTF and higher vs lower doses of HM. We selected studies that used fortified HM and compared that with a PTF; studies comparing unfortified HM and term formula were excluded. Experimental and observational studies were pooled separately. The GRADE system was used to evaluate risk of bias and certainty of evidence. Forty-four studies were included with 37 (n =9,963 infants) included in the meta-analyses. In general, due to poor quality studies, evidence of the effect of any HM feeds or higher versus lower doses of HM was inconclusive. There was a possible effect that lower doses of HM compared with higher doses of HM improved weight gain during the hospital admission, and separately, a possible effect of increased head circumference growth in infants fed EPTF vs any HM. The clinical significance of this is unclear. There was insufficient evidence to determine the effects of an exclusive HM diet on any outcomes.

The aim of this study was to determine the extent to which the Tyme Wear smart shirt is as reliable and valid in detecting personalized ventilatory thresholds when compared to the Parvo Medics TrueOne 2400. In this validation study, 19 subjects were recruited to conduct two graded exercise test (GXT) trials. Each GXT trial was separated by seven to ten days of rest. During the GXT, gas exchange and heart rate data were collected by the TrueOne 2400 (TRUE) in addition to the ventilation data collected by the Tyme Wear smart shirt (S-PRED). Gas exchange data from TRUE was used to detect VT1 and VT2. TRUE and S-PRED VT1 and VT2 were compared to determine the reliability and validity of the smart shirt. Of the 19 subjects, data from 15 subjects were used during analysis. S-PRED exhibited excellent (ICC &gt; 0.90) reliability for detection of VT1 and VT2 utilizing time point and workload and moderate (0.90 &gt; ICC &gt; 0.75 ) reliability utilizing heart rate. TRUE exhibited excellent reliability for detection of VT1 and VT2 utilizing time point, workload, and heart rate. When compared to TRUE, S-PRED appears to underestimate the VT1 workload (p &gt; 0.05) across both trials and heart rate (p &lt; 0.05) for trial 1. However, S-PRED appears to underestimate VT2 workload (p &lt; 0.05) and heart rate (p &lt; 0.05) across both trials. The result from this study suggests that the Tyme Wear smart shirt is less valid but is comparable in reliability when compared to the gold standard. Moreover, despite the underestimation of S-PRED VT1 and VT2, the S-PRED detected personalized ventilatory thresholds will provide an adequate training workload for most individuals. In conclusion, the Tyme Wear smart shirt provides easily accessible testing to establish threshold-guided training zones but does not devalue the long-standing laboratory equivalent.

This manuscript critically reviews the design and delivery of spray-dried particles for the achievement of high total lung doses (TLD) with a portable dry powder inhaler. We introduce a new metric termed the product density, which is simply the TLD of a drug divided by the volume of the receptacle it is contained within. The product density is given by the product of three terms: the packing density (the mass of powder divided by the volume of the receptacle), the drug loading (the mass of drug divided by the mass of powder), and the aerosol performance (the TLD divided by the mass of drug). This manuscript discusses strategies for maximizing each of these terms. Spray drying at low drying rates with small amounts of a shell-forming excipient (low Peclet Number) leads to formation of higher density particles with high packing densities. This enables ultrahigh TLD (>100 mg of drug) to be achieved from a single receptacle. Emptying of powder from capsules is directly proportional to the mass of powder in the receptacle, requiring an inhaled volume of about 1 L for fill masses between 40 and 50 mg and up to 3.2 L for a fill mass of 150 mg.

Coronaviruses (CoVs) are enveloped positive-sense single-stranded RNA viruses with a genome 27-31kbases in length. Critical genes include the spike (S), envelope (E), membrane (M), nucleocapsid (N) and 9 accessory open reading frames encoding for non-structural proteins (NSPs) that have multiple roles in the replication cycle and immune evasion (1). There are 7 known human CoVs that most likely appeared after zoonotic transfer, the most recent being SARS-CoV-2 responsible for the Covid-19 pandemic. Antivirals that have been approved by the FDA for use against Covid-19 such as Paxlovid can potentially target and successfully inhibit the main protease (MPro) activity of multiple human CoVs, however alternative proteomes encoded by CoV genomes have a closer genetic similarity to each other, suggesting that antivirals could be developed now that target future CoVs. New zoonotic introductions of CoVs to humans are inevitable and unpredictable. Therefore, new antivirals are required to control not only the next human CoV outbreak, but also the 4 common human CoVs (229E, OC43, NL63, HKU1) that circulate frequently and to contain sporadic outbreaks of the severe human CoVs (SARS-CoV, MERS and SARS-CoV-2). The current study found that emerging antiviral drugs, such as Paxlovid, have only been proven to target SARS-CoV-2. Other drugs which have the potential to target other human CoVs, are still within clinical trial and are not yet available for public use. Monoclonal antibody (mAb) treatment and vaccines for SARS-CoV-2 can reduce mortality and hospitalisation rates, however they target the Spike protein whose sequence mutates frequently and drifts. Spike also is not applicable for targeting other HCoVs as these are not well conserved sequences among human CoVs. Thus, there is a need for readily available treatments globally that target all 7 human CoVs and improve the preparedness for inevitable future outbreaks. Here we discuss antiviral research contributing to the control of common and severe CoV replication and transmission, including the current SARS-CoV-2 outbreak. The aim was to identify common features of CoVs for antivirals, biologics and vaccines that could reduce the scientific, political, economic and public health strain caused by CoV outbreaks now and in the future.

Over the past decade and a half, dynamic functional imaging has revolutionized the neuroimaging field. Since 2009, it has revealed low dimensional brain connectivity measures, has identified potential common human spatial connectivity states, has tracked the transition patterns of these states, and has demonstrated meaningful alterations in these transition and spatial patterns in neurological disorders, psychiatric disorders, and over the course of development. Recently, researchers have begun to analyze this data from the perspective of dynamic system and information theory in the hopes of understanding how these dynamics support less easily quantified processes, such as information processing, cortical hierarchy, and consciousness. Consciousness, in particular, appears to be strongly linked to entropy production in the brain. Little attention has been paid to the effects of psychiatric disease on entropy production in the human brain, however. Even disorders characterized by substantial changes in conscious experience have not been widely analyzed from this perspective. We begin to rectify this by examining the complexity of subject trajectories in state space through the lens of information theory. Specifically, we identify a basis for the dynamic functional connectivity state space and track subject trajectories through this space over the course of the scan. The dynamic complexity of these trajectories is assessed along each dimension of the proposed basis space. Using these estimates, we demonstrate that schizophrenia patients display substantially simpler trajectories than demographically matched healthy controls, and that this drop in complexity concentrates along specific dimensions. We also demonstrate that entropy generation in at least one of these dimensions is linked to cognitive performance. Overall, results suggest great value in applying dynamic systems theory to problems of neuroimaging and reveal a substantial drop in the complexity of schizophrenia patients’ brain function.

The cancelation factor (CF) is a model for the ratio between gravity wave perturbations in the airglow intensity to that in the ambient temperature. The CF model allows to estimate the momentum and energy flux of gravity waves seen in nightglow images as well as the divergence of these fluxes due to waves propagating through the mesosphere and lower thermosphere region, where the nightglow and the Na layers are located. This study uses a set of T/W Na Lidar data and zenith nightglow image observations of the OH and O(1S) emissions to test and validate the CF model from the experimental perspective. The dataset analyzed was obtained during campaigns carried out at the Andes Lidar Observatory (ALO), Chile in 2015, 2016, and 2017. The CF modeled function was compared with observed points from an empirical method for vertically propagating waves that calculates directly the ratio of the gravity wave amplitude seen in nightglow images to the wave amplitude seen in lidar temperatures. We show that the CF analytical relationship underestimates the observed results generally. However, the O(1S) emission line has better agreement respect to the theoretical value due to simpler nightglow photochemistry. In contrast, the observed CF ratio from the OH emission deviates by a factor of two from the modeled asymptotic value.

Background: Previous studies have associated slowed ventricular conduction in the arrhythmogenesis mediated by the gap junction and sodium channel inhibitor heptanol in mouse hearts but did not study the propagation patterns that might contribute to the arrhythmic substrate. This study used a multi-electrode array mapping technique, to further investigate different conduction abnormalities in Langendorff-perfused mouse hearts exposed to 0.1 or 2 mM heptanol. Methods: Multi-electrode array recordings were made from the left ventricular epicardium in spontaneously beating hearts, during right ventricular regular 8 Hz pacing or S1S2 pacing. Results: In spontaneously beating hearts, heptanol at 0.1 and 2 mM significantly reduced the heart rate from 314±25 to 189±24 and 157±7 bpm, respectively (ANOVA, P<0.05 and P<0.001). During regular 8 Hz pacing, Mean LATs were increased by 0.1 and 2 mM heptanol from 7.1±2.2 ms to 19.9±5.0 ms (P<0.05) and 18.4±5.7 ms (P<0.05). The standard deviation of mean LATs was increased from 2.5±0.8 ms to 10.3±4.0 ms and 8.0±2.5 ms (P< 0.05), and the median of phase differences was significantly increased from 1.7±1.1 ms to 13.9±7.8 ms and 12.1±5.0 ms by 0.1 and 2 mM heptanol (P<0.05). P5 took a value of 0.2±0.1 ms and was not significantly altered by heptanol at 0.1 or 2 mM (1.1±0.9 ms and 0.9±0.5 ms, P>0.05). P50 was increased from 7.3±2.7 ms to 24.0±12.0 ms by 0.1 mM heptanol and then to 22.5±7.5 ms by 2 mM heptanol (P< 0.05). P95 was increased from 1.7±1.1 ms to 13.9±7.8 ms by 0.1 mM heptanol and to 12.1±5.0 ms by 2 mM heptanol (P<0.05). These changes led to increases in the absolute inhomogeneity in conduction (P5-95) from 7.1±2.6 ms to 31.4±11.3 ms, 2 mM: 21.6±7.2 ms, respectively (P<0.05). The inhomogeneity index (P5-95/P50) was significantly reduced from 3.7±1.2 to 3.1±0.8 by 0.1 mM and then to 3.3±0.9 by 2 mM heptanol (P<0.05). Conclusion: Increased activation latencies, reduced CVs and increased dispersion index of conduction were associated with both spontaneous and induced ventricular arrhythmias.

Evaluation of the effects of a high-frequency acceleration (HFA) device on patient pain response to orthodontic forces. A multi-centered trial investigating pain sensitivity to orthodontic forces on 75 subjects at 4 study centers. Subjects underwent clear aligner treatment, with or without adjunctive HFA and documented their pain intensity using the validated NRS10 numeric rating scale. In-Office and At-Home ratings were measured separately for each subject for immediate and extended effect evaluations. Use of HFA devices in conjunction with clear aligner orthodontic treatment demonstrated significant reduction in subjects’ recorded pain ratings vs controls within 5 minutes of aligner exchange, (p = 0.006) and significant reduction in recorded pain ratings vs controls over a 7-day period following aligner exchange (p = 0.018). A 99.6% daily compliance rate with at home use of the HFA device was recorded for all subjects in the study. HFA significantly reduces pain attributed to orthodontic force. HFA delivers clinically significant immediate pain relief, and clinically significant extended pain relief over the 7 days following adjustment.

Culture exploits the acquisition of meaningful content by crafting regimes of shared attention, determining what is relevant, valuable, and salient. Culture changes the field of relevant social affordances worthy of being acted upon in a context-sensitive manner. When relevant affordances are highly weighted, their attentional capture and their salience increase the probability of them being enacted due to the associated expectation for minimizing prediction error. This process is known as active inference. In the digital era, individuals need to infer the action-related attributes of digital cues, here characterized as digital affordances. The digital affordances of digital social platforms are of particular interest here. Digital social affordances are defined as online possibilities of social interactions. By their own nature, these are salient because they are related to social interactions and relevant social cues. However, the problem of digital social platforms is that they are not equivalent to situated social interactions because their structure is built, mediated, and defined by third-parties with diverse interests. The third-parties behind the digital social platforms are using the same mechanism exploited by culture to manipulate the shared patterns of attention. Moreover, digital social platforms are deliberately designed to be hyper-stimulating, making digital social affordances highly rewarding and increasingly salient. This appropriation, for economic purposes, is an issue of great importance, especially as the COVID-19 pandemic brought deep global changes, pushing societies to an online digital way of life. Here, we examined different types of digital social affordances under an active inference view, placing them into two categories, those for self-identity formation, and those for belief-updating. This paper aims to analyze digital social affordances in light of the prediction error dynamics they might elicit to their users. Although each of the analyzed digital social affordances allows different epistemic and instrumental digital actions, they all share the characteristic of having an "easy" and a fast expected rate of error reduction. Here, we aim to provide a new hypothesis about how the design behind digital social affordances is built on our natural attractiveness to minimize prediction error and the resulting positive embodied feelings when doing so. Finally, it is suggested that because digital social affordances are becoming highly weighted in the field of affordances, this might be putting at risk our context-sensitive grip on a rich, dynamic and varied field of relevant affordances.

The prevalence of type-2 diabetes mellitus (T2D) is increasing worldwide and there are no long-term preventive strategies to stop this growth. Emerging research shows that perturbations in the gut microbiome significantly contribute to the development of T2D, while microbiome modulators may be beneficial for T2D prevention. However, microbiome modulators that are effective, safe, affordable, and able to be integrated daily in the diet are not yet available. Based on our previous pro- and prebiotic studies, we developed a novel synbiotic yogurt comprised of human-origin probiotics and plant-based prebiotics and investigated its impact on diet- and streptozotocin-induced T2D in mice. We compared the effects of our synbiotic yogurt to those of a commercially-available yogurt (control yogurt). Interestingly, we found that feeding of this synbiotic yogurt significantly reduced the development of hyperglycemia (diabetes) in response to high-fat diet feeding and streptozotocin compared to milk-fed controls. Surprisingly, the control yogurt exacerbated diabetes progression. Synbiotic yogurt beneficially modulated the composition of gut microbiota compared to milk; conversely, the control yogurt negatively modulated the gut microbiota by significantly increasing the abundance of detrimental bacteria like Proteobacteria and Enterobacteriaceae. In addition, the synbiotic yogurt protected intact pancreatic islet morphology compared to the milk control, while the commercial yogurt demonstrated worse effects on pancreatic physiology. These results suggest that our newly developed synbiotic yogurt protects against diabetes in mice and can be used as a modality to prevent diabetes progression.

Antibiotic resistance is a persistent and growing concern. Our objective was to analyze antibiotic prescribing in the United States (US) in the Medical Expenditure Panel System (MEPS) and to Medicaid patients. We obtained total MEPS prescriptions for eight antibiotics from 2013 to 2020. We extracted prescribing rates per 1,000 Medicaid enrollees for two years, 2018 and 2019, for four broad spectrum (azithromycin, ciprofloxacin, levofloxacin, and moxifloxacin) and four narrow spectrum (amoxicillin, cephalexin, doxycycline, and trimethoprim/sulfamethoxazole) antibiotics. Antibiotics in MEPS decreased from 2013 to 2020 by -38.7% with a larger decline for broad (-53.7%) than narrow (-23.5%) spectrum. Antibiotic prescriptions in Medicaid decreased by -6.7%. Amoxicillin was the predominant antibiotic followed by azithromycin, cephalexin, trimethoprim/sulfamethoxazole, doxycycline, ciprofloxacin, levofloxacin, and moxifloxacin. Substantial geographic variation in antibiotic prescribing existed with 2.8-fold between the highest (Kentucky = 855/1,000) and lowest (Oregon = 299) states. The South prescribed 52.2% more antibiotics (580/1,000) than the West (381/1,000). There were significant correlations across states in antibiotic prescribing. This study identified sizable disparities by geography in prescribing rates of eight antibiotics with over three-fold state level differences. Areas with high antibiotic prescribing rates, particularly for outpatients, may benefit from stewardship programs to reduce potentially unnecessary prescribing.

The United States is plagued with the highest rates of preventable metabolic diseases it has ever seen, and while poor nutrition is increasingly recognized as a critical contributing factor, good nutrition has been shown to be a potent factor in prevention and management of these illnesses. Notably, nutrition is inextricably intertwined with farming practices and the stewardship of our environment – particularly its soil. In this proposal, we propose a method to expose medical students to basic agricultural and environmental knowledge regarding the production of food, as well as educate them in practical nutrition education within the interactive, case-based, and longitudinal preclinical curriculum at Case Western Reserve University School of Medicine (CWRU SOM). We propose a two-part approach; first: integrating relevant topics in nutrition, culinary medicine, and farming practices into the preclinical blocks through Official Learning Objectives, and second: an optional 8-week, zero credit elective for students interested in pursuing a deeper understanding of these topics. Through these interventions, we believe courses like this will support a generation of physicians able to understand health from soil to plate with a consideration for the environment in addition to exemplifying healthful lifestyles themselves. We believe these kinds of future physicians will be the most effective in treating (and ideally reversing) the chronic disease epidemic.

The volume of vehicular traffic in large cities has increased in recent years, the devices that collect vehicular GPS data such as cameras, GPS receivers and others generate millions of records at every instant of time generating problems in processing and storage of these data which becomes important for researchers. Intelligent Transportation Systems perform vehicle monitoring and control by collecting GPS trajectories, this large volume of information is necessary to have an optimal storage process. Its processing by means of compression techniques and simplification algorithms allow to reduce the necessary storage space. This paper presents a GPS trajectory simplification algorithm that considers noise reduction, point simplification and analysis of road network information. The results obtained on two data sets from the cities of California and Beijing are satisfactory, achieving a higher compression ratio without affecting data quality

Pyrolysis is a combustion process of woody biomass conducted under low or no oxygen conditions. New innovations and the need to limit open burning has resulted in numerous mobile and fixed plant pyrolysis methods that burn a variety of woody residues. Production technologies that reduce the need for open burning, the main source of potential pollutants, fall under the regulations in the Clean Air Act of 1990. This Act is the legal instrument to regulate air pollution at its source across the United States of America and it is implemented and enforced through the Environmental Protection Agency, in coordination with sister agencies. One newer innovation for reducing woody residues and emissions is an air curtain incinerator. Currently, the Clean Air Act regulates stationary solid waste incinerators, and this is also applied to mobile air curtain incinerators burning woody biomass. However, other woody biochar production methods (e.g., flame cap kilns) are not subject to these regulations. Discrepancies in the interpretation of definitions related to incineration and pyrolysis and the myriad of differences related to stationary and mobile air curtain incinerators, type of waste wood from construction activities, forest residues, and other types of clean wood make the permitting regulations confusing as permits can vary by jurisdiction. This review summarizes the current policies, regulations, and directives related to in-woods biochar production and the required permits.

Globally, over the past several months millions of persons contracted the coronavirus disease 2019 (COVID-19) resulting in significant mortality. Health care systems are negatively impacted including the care of individuals with cancers and other chronic diseases such as chronic active hepatitis, cirrhosis and hepatocellular carcinoma. There are various probable pathogenic mechanisms that have been presented to account for liver injury in COVID-19 patients such as hepatotoxicity cause by therapeutic drugs, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection of the bile duct cells and hepatocytes, hypoxia and systemic inflammatory response. Liver biochemistry tests such as AST, ALT, GGT and ALP are deranged in COVID-19 patients with liver injury. Hepatocellular damage results in the elevation of serum AST and ALT levels in early onset disease while a cholestatic pattern that develops as the disease progress causes higher levels of ALP, GGT, direct and total bilirubin. These liver biochemistry tests are prognostic markers of disease severity and should be carefully monitored in COVID-19 patients. We conducted a systematic review of abnormal liver biochemistry tests in COVID-19 and the possible pathogenesis involved. Significant findings regarding the severity, hepatocellular pattern, incidence and related clinical outcomes in COVID-19 patients are highlighted.

Polylactic Acid (PLA) is an organic polymer commonly used in fused deposition (FDM) printing and biomedical scaffolding that is biocompatible and immunologically inert. However, variations in source material quality and chemistry make it necessary to characterize the filament and determine potential changes in chemistry occurring as a result of the FDM process. We used several spectroscopic techniques, including laser confocal microscopy, Fourier-Transform Infrared (FTIR) spectroscopy and photoacousitc FTIR spectroscopy, Raman spectroscopy, and X-ray photoelectron Spectroscopy (XPS) in order to characterize both the bulk and surface chemistry of the source material and printed samples. Scanning Electron Microscopy (SEM) and Differential Scanning Calorimetry (DSC) were used to characterize morphology, crystallinity, and the glass transition temperature following printing. Analysis revealed calcium carbonate-based additives which were reacted with organic ligands and potentially trace metal impurities, both before and following printing. These additives became concentrated in voids in the printed structure. This finding is important for biomedical applications as carbonate will impact subsequent cell growth on printed tissue scaffolds. Results of chemical analysis also provided evidence of the hygroscopic nature of the source material and oxidation of the printed surface, and SEM imaging revealed micro and sub-micron scale roughness that will also impact potential applications.

Abstract: 1) Background. This research examined feasibility, acceptability and outcomes of delivering a 6-week yoga-based meditation intervention to clinical teams of hospice professionals (HPs) at a large non-profit hospice organization. The intervention was designed to increase mind-body integration and combat burnout. The manuscript was written for different audiences including research scientists who study interoception, burnout, meditation, or yoga, designers of meditation interventions, and hospice organizations looking for ways to mitigate HP burnout. 2) Methods. The intervention was launched within clinical teams, beginning with a half hour online introduction to the program and exposure to the week 1 meditation at each team’s monthly all-staff meeting. Throughout the program, HPs could access the meditations on their own via their workplace computers, tablets, and smartphones. Online pre- and post-intervention surveys with 151 HPs assessed burnout using the Professional Fulfillment Index and mind-body integration using the Multidimensional Assessment of Interoceptive Awareness sub-scales. 3) Results. Half of HPs expressed a desire to continue to have access to the meditations after the 6-week program ended. Due to covid-19 work from home restrictions, three-fourth of HPs did a meditation at home, 29% in a car between patient visits (not while driving), and 23% at the office. Higher interoceptive awareness was significantly related to lower burnout, particularly lower work exhaustion. Meditation frequency was significantly related to higher interoceptive awareness but not to burnout. 4) Conclusions. Findings showed that yoga-based meditation intervention was feasible and acceptable and associated with higher interoceptive awareness. The results point to a role for interoceptive awareness in reducing the risk for burnout.

Curcumin [1,7-bis(4-hydroxy-3-methoxyphenyl)-1,6-heptadien-3,5-dione], a component of Curcuma longa L. rhizomes, displays various biological and pharmacological activities. However, it is poorly bioavailable and unstable in physiological pH, which has led more stable and effective curcumin analogs (e.g., monoketone curcuminoids, or MKCs) to be synthesized, and their biological activities to be described. In this review, we cover papers published between 2019 and 2023 on the antimicrobial, anticancer, antioxidant, and antiparasitic actions as well as other less common MKC biological and pharmacological activities. We also address the Claisen-Schmidt condensation as a standard procedure to synthesize MKCs.

Herpes simplex virus type 1 (HSV-1) is a lifelong pathogen characterized by asymptomatic latent infection in the trigeminal ganglia (TG) with periodic outbreaks of cold sores caused by virus reactivation in the TG and subsequent replication in the oral mucosa. While antiviral therapies can provide relief from cold sores, they are unable to eliminate HSV-1. We provide experimental results that highlight non-thermal plasma (NTP) as a new alternative therapy for HSV-1 infection that would resolve cold sores faster and reduce the establishment of latent infection in the TG. Additionally, this study is the first to explore the use of NTP as a therapy that can both treat and prevent human viral infections. We investigated the antiviral effect of NTP using an in vitro model for HSV-1 cold sores, involving the application of NTP from two separate devices to cell-free HSV-1, HSV-1-infected cells, and uninfected cells. We found NTP reduced the infectivity of cell-free HSV-1, reduced viral replication in HSV-1-infected cells, and diminished the susceptibility of uninfected cells to HSV-1 infection. This triad of antiviral mechanisms of action suggest the potential of NTP as a therapeutic agent effective against HSV-1 infection.

Urolithins (e.g., UroA and B) are gut microbiota-derived metabolites of the natural polyphenol ellagic acid. Urolithins are associated with various health benefits, including attenuation of inflammatory signaling, anti-cancer effects and repression of lipid accumulation. The molecular mechanisms underlying the beneficial effects of urolithins remain unclear. We hypothesize that some of the human health benefits of urolithins are mediated through the aryl hydrocarbon receptor (AHR). Utilizing a cell-based reporter system, we tested urolithins for the capacity to modulate AHR activity. Cytochrome P450 1A1 (CYP1A1) mRNA levels were assessed by real-time quantitative polymerase chain reaction. Competitive ligand binding assays were performed to determine whether UroA is a direct ligand for the AHR. Subcellular AHR protein levels were examined utilizing immunoblotting analysis. AHR expression was repressed in Caco-2 cells by siRNA transfection to investigate AHR-dependency. UroA and B were able to antagonize 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD)-induced AHR-mediated transcriptional activity. Furthermore, UroA and B attenuated TCCD-mediated stimulation of CYP1A1 mRNA levels. In addition, competitive ligand binding assays characterized UroA as a direct AHR ligand. Consistent with other AHR antagonists, UroA failed to induce AHR retention in the nucleus. AHR is necessary for UroA-mediated attenuation of cytokine-induced interleukin 6 (IL6) and prostaglandin-endoperoxide synthase 2 (PTGS2) expression in Caco-2 cells. Here we identified UroA as the first dietary-derived human selective AHR antagonist produced by the gut microbiota through multi-step metabolism. Furthermore, previously reported anti-inflammatory activity of UroA may at least in part be mediated through AHR.

Phylogenies depict shared evolutionary patterns and structures on a tree topology, enabling the identification of hierarchical and historical relationships. Recent analyses indicate that phylogenetic signals extend beyond the primary structure of protein or DNA, and various aspects of codon usage biases are phylogenetically conserved. Several functional biases exist within genes, including the number of codons that are used, the position of the codons, and the overall nucleotide composition of the genome. Codon usage biases can significantly affect transcription and translational efficiencies, leading to differential gene expression. Although systematic codon usage biases originate from the overall GC content of a species, ramp sequences, codon aversion, codon pairing, and tRNA competition also significantly affect gene expression and are phylogenetically conserved. We review recent advances in analyzing codon usage biases and their implications in phylogenomics. We first outline common phylogenomic techniques. Next, we identify several codon usage biases and their effects on secondary structure, gene expression, and implications in phylogenetics. Finally, we suggest how codon usage biases can be included in phylogenomics. By incorporating various codon usage biases in common phylogenomic algorithms, we propose that we can significantly improve tree inference. Since codon usage biases have significant biological implications, they should be considered in conjunction with other phylogenetic algorithms.

Vehicular traffic in urban areas continues to be a constant challenge today, due to the continuous population growth and the increase of vehicles in circulation. Vehicular congestion, as a recurrent problem, generates a negative impact on urban mobility and citizens’ quality of life. It is hypothesized that a dynamic clustering method of vehicle trajectory data can provide an accurate and up-to-date representation of real-time traffic behavior. To evaluate this hypothesis, data were collected from three different cities: San Francisco, Rome and Guayaquil. A dynamic clustering algorithm was applied to identify traffic congestion patterns and an indicator was applied to identify and evaluate the congestion conditions of the areas. The results show a high precision and recall in congestion classification compared to a method based on static cells.

Recently, NOAA has included GNSS (Global Navigation Satellite System) Radio Occultation (RO) data as one of the crucial long-term observables for weather and climate applications. To include more GNSS RO data in the numerical weather prediction system, the NOAA Commercial Weather Data Pilot program (CWDP) started to explore the commercial RO data available on the market. After two rounds of pilot studies, the CDWP decided to award the first Indefinite Delivery Indefinite Quantity (IDIQ) contract to GeoOptics and Spire Incs. in 2020. This study examines the quality of Spire data products for weather and climate applications. Spire RO data are collected from commercial CubeSats through careful comparison with the data from Formosa Satellite Mission 7–Constellation Observing System for Meteorology, Ionosphere, and Climate-2 (COSMIC-2), ERA-5, and high-quality radiosonde data. The results demonstrated that although with lower Signal-Noise-Ratio (SNR) in general, the pattern of the lowest penetration height for Spire is similar to those for COSMIC-2. The Spire and COSMIC-2 penetrate heights are between 0.6 and 0.8 km altitude at the tropical oceans. Although using different GNSS RO receivers, the precision of Spire STRASP receivers is of the same quality as those of COSMIC-2 Global Positioning System - GPS, GALILEO, and GLObal NAvigation Satellite System – GLONASS (TGRS) receivers. The retrieval accuracy from Spire is very compatible with those from COSMIC-2. We validated Spire temperature and water vapor profiles by comparing them with collocated radiosonde data. Generally, over the height region between 8 km and 16.5 km, the Spire temperature profiles match those from RS41 RAOB very well with temperature biases &lt; 0.02 K. Over the height range from 17.8 to 26.4 km, the temperature differences are ~-0.034 K with RS41 RAOB being warmer. We also estimated the error covariance matrix for Spire, COSMIC-2, and KOMPSAT-5. Results showed that the COSMIC-2 estimated error covariance values are slightly more significant over the oceans at the mid-latitudes (45oN-30oN and 30oS-45oS), which may also be owing to COSMIC-2 SNR being lower at those latitudinal zones.

Background and Objectives: Obesity-related elevated body mass index (BMI) across life is associated with chronic low-grade inflammation and increased levels of C-reactive protein (CRP) in blood. CRP is a marker and promoter of inflammation. The objectives of this study were to examine the effect of obesity on the relationship between peripheral and gingival CRP levels and examine the effects of gingival CRP levels on gingival fluid inflammatory cytokines in periodontitis resistant obese individuals. Materials and Methods: Thirty-nine, periodontally healthy subjects were enrolled. Based on BMI scores, 20 subjects were categorized as lean and 19 as obese. A comprehensive periodontal examination was performed. Gingival crevicular fluid (GCF) and blood samples were collected. Both GCF and blood samples were assessed for interleukin-1β (IL-1β), interleukin-6 (IL-6), interleukin-8 (IL-8), tumor necrosis factor-α (TNF-α), interleukin-10 (IL-10), interleukin-17A (IL-17A) and CRP. Results: GCF CRP levels were significantly higher in obese than lean individuals. No statistically significant differences were noted between the two groups in both GCF and blood on any of the inflammatory cytokine levels. IL-17A was not detected in GCF of most subjects in both groups. GCF CRP levels were positively associated with blood CRP levels, the association tended to be stronger in obese individuals. GCF CRP showed no associations with GCF IL-10 in both groups. Although GCF CRP levels positively associated with multiple GCF inflammatory cytokines (e.g., IL-1β, IL-6, IL-8 and TNF-α) in all subjects, the associations tended to be weaker in obese individuals (e.g., IL-1β, IL-6, TNF-α). Furthermore, the levels of GCF inflammatory cytokines IL-6 and TNF-α were depressed in obese individuals. Conclusions: Obesity unfavorably influences the relationship between blood and GCF CRP levels and promotes increased CRP levels in GCF. Collectively, the findings suggest a dysregulated inflammatory cytokine response in the gingival tissues of obese individuals.

Software testing is an integral yet time-consuming component of software development, and even with capable software testing resources (technology and people), it is still regarded as problematic. Test automation is widely being utilised within the software industry to provide increased testing capacity to ensure high product quality and reliability. In this paper, we are specifically addressing automated testing whereby test cases are manually written. Test automation has its benefits, drawbacks, and impacts on different stages of development. Furthermore, there is often a disconnect between non-technical and technical roles, where non-technical roles (e.g., management) predominantly strive to reduce costs and delivery time whereas technical roles are often driven by quality and completeness. Although it is widely understood that there are challenges with adopting and using automated testing, there is a lack of evidence to understand the different attitudes toward automated testing (AtAT), focusing specifically on why it is not adopted. In this paper, the authors have surveyed practitioners within the software industry from different roles to determine common trends and draw conclusions. A two-stage approach is presented, comprising a comprehensive descriptive analysis and the use of Principle Component Analysis. In total, 81 participants were provided with a series of 22 questions and their responses are compared against job role types and experience levels. In summary, 6 key findings are presented covering expertise, time, cost, tools and techniques, utilisation, organisation, and capacity

Chronic wasting disease is a fatal transmissible spongiform encephalopathy (TSE) of cervids caused by a misfolded variant of the normal cellular prion protein, and is closely related to sheep scrapie. Variations in a host’s prion gene, PRNP, and its primary protein structure, dramatically affect susceptibility to specific prion disorders, and breeding for PRNP variants that prevent scrapie infection has led to steep declines in the disease in North American and European sheep. While resistant alleles have been identified in cervids, a PRNP variant that completely prevents CWD has not yet been identified. Thus, control of the disease in farmed herds traditionally relies on quarantine and depopulation. In CWD-endemic areas, depopulation of private herds becomes challenging to justify, leading to opportunities to manage the disease in situ. In the present study, we developed a selective breeding program for farmed white-tailed deer in a CWD-endemic area, focused on reducing frequencies of highly susceptible PRNP variants and introducing animals with less-susceptible variants into historically high prevalence areas. We found that breeding followed predictable Mendelian inheritance, and early data support our project’s utility in reducing CWD prevalence. This project represents a novel approach to CWD management, with future efforts building on these findings.

Feline immunodeficiency virus (FIV) is a naturally-occurring retrovirus that infects domestic and non-domestic feline species, producing progressive immune depletion that results in an acquired immunodeficiency syndrome (AIDS). Much has been learned about FIV since it was first described in 1987, particularly in regard to its application as a model to study the closely related lentivirus, human immunodeficiency virus (HIV). In particular, FIV and HIV share remarkable structure and sequence organization, utilize parallel modes of receptor-mediated entry, and result in a similar spectrum of immunodeficiency-related diseases due to analogous modes of immune dysfunction. This review summarizes current knowledge of FIV infection kinetics and mechanisms of immune dysfunction in relation to opportunistic disease, specifically in regard to studying HIV pathogenesis. Furthermore, we present data which highlight changes in the oral microbiota and oral immune system during FIV infection, and outline the potential for the feline model of oral AIDS manifestations to elucidate pathogenic mechanisms of HIV-induced oral disease. Finally, we discuss advances in molecular biology, vaccine development, neurologic dysfunction, and the ability to apply pharmacologic interventions and sophisticated imaging technologies to study experimental and naturally occurring FIV, which provide an excellent, but often overlooked resource for advancing therapies and management of HIV/AIDS.

Additive manufacturing (AM) provides opportunities to design objects differently than traditional manufacturing methods allow, but only if designers understand the possibilities AM presents. In this study, we examined whether an AM workshop combined with an idea generation session could inspire engineering professionals to use AM solutions to solve current technical problems they face. All subjects were employees at an organization that will be referred to as Company X, a multinational commercial organization based in North America. During the study, we collected ideas for 24 projects generated before and after a training workshop focused on design for AM. In the workshop, we provided three hours of instruction about design for two metal-based AM processes. The participants’ ideas were assessed using four specific metrics: (1) cost, (2) time,(3) completeness of solution, and (4) quality, which was a function of feasibility, usefulness, and novelty. Using these data, we explored whether the workshop was effective in inspiring the participants to use AM methods and techniques from AM research in their concept generation and whether participants’ AM solutions showed improvement in cost, implementation time, and quality over non-AM designs generated before the workshop.

Freezing of gait (FOG), a debilitating symptom of Parkinson’s disease (PD), can be safely studied using the stepping in place (SIP) task. However, clinical, visual identification of FOG during SIP is subjective and time consuming, and automatic FOG detection during SIP currently requires measuring center of pressure on dual force plates. This study examines whether FOG elicited during SIP in 10 individuals with PD could be reliably detected using kinematic data measured from wearable inertial measurement unit sensors (IMUs). A general, logistic regression model (AUC = 0.81) determined that three gait parameters together were overall the most robust predictors of FOG during SIP: arrhythmicity, swing time coefficient of variation, and swing angular range. Participant-specific models revealed varying sets of gait parameters that best predicted FOG for each participant, highlighting variable FOG behaviors, and demonstrated equal or better performance for 6 out of the 10 participants, suggesting the opportunity for model personalization. The results of this study demonstrated that gait parameters measured from wearable IMUs reliably detected FOG during SIP, and the general and participant-specific gait parameters allude to variable FOG behaviors that could inform more personalized approaches for treatment of FOG and gait impairment in PD.

Human papillomavirus (HPV) can potentially compromise both unassisted conception and success rates with assisted reproductive technology (ART). We aimed to evaluate the rates of HPV vaccination among women presenting for fertility care. This was a prospective study analyzing a self-reported intake form completed by all new patients presenting to a fertility clinic. The primary outcome was HPV vaccination status. Among the 523 new patients included in this study 172 (32.9%) were fully vaccinated, 237 (45.3%) were unvaccinated, and 95 (18.2%) patients didn’t respond. There was a significant age difference between fully vaccinated patients (33.1 years) compared to unvaccinated patients (37.4 years) p&lt;0.001 and a significant difference in gravidity between fully vaccinated patients (average 0.65) and unvaccinated patients (average 1.11) p=0.0005. No significant association was found between HPV vaccination status and history of abnormal Pap smears or relationship status (single vs. married). Less than half of patients presenting to our fertility center were vaccinated against HPV, despite being eligible to receive the vaccine. Younger patients with lower gravidity were more likely to be vaccinated against HPV than older patients with higher gravidity. Reproductive Endocrinologists have the opportunity to recommend HPV vaccination for eligible patients presenting for fertility care.

Background: Recent work has investigated significant force transmission between the compo-nents of myofascial chains. Misalignments in the body due to fascial thickening and shortening can therefore lead to complex compensatory patterns. For the treatment of such nonlinear cause-effect pathology, a comprehensive neuro-musculoskeletal therapy such as the Rolf Meth-od of Structural Integration (SI) could be targeted. Methods: A total of 727 subjects were retro-spectively screened from the medical records of an SI practice over a 23-year period. 383 subjects who had completed 10 basic SI sessions met eligibility criteria and were assessed for active range of motion (AROM) of the shoulder and hip before and after SI treatment. Results: Shoulder flex-ion, external and internal rotation, and hip flexion improved significantly (all p < 0.0001) after 10 SI sessions. Left shoulder flexion and external rotation of both shoulders increased more in men than in women (p < 0.0001), but were not affected by age. Conclusions: SI intervention produces multiple changes in the components of myofascial chains that could help maintain upright pos-ture in humans and reduce inadequate compensatory patterns. SI affects differently the outcome of some AROM parameters in women and men.

Red beetroot, is a well-recognized and established source of bioactives (e.g., betalains and polyphenols) with anti-inflammatory and antimicrobial properties. It is proposed as a potential alternative to zinc oxide, with a focus on gut microbiota modulation and metabolite production. In this study, weaned pigs aged 28-days were fed either a control diet, diet supplemented with zinc oxide (3,000 mg/kg), or 2% and 4% pulverized whole red beetroot (CON, ZNO, RB2 and RB4; respectively) for 14 days. After the pigs were euthanized, blood and digesta samples were collected for microbial composition and metabolite analyses. Results showed, red beetroot supplemented diet at 2% improved the gut microbial richness relative to other diets, but marginally influenced the caecal microbial diversity compared to zinc oxide supplemented diet. Further increase in red beetroot levels (4% -RB4) lead to loss of caecal diversity, decreased short chain fatty acids and secondary bile acid concentrations. An increased Proteobacteria abundance, presumably due to increased lactate/lactic acid producing bacteria was also observed. Summarily, red beetroot contains several components conceived to improve the gut microbiota and metabolite output of weaned pigs. Future studies investigating individual components in red beetroot will better elucidate their contributions to gut microbiota modulation and pig health.

There is limited evidence for the association between malnutrition and hospital mortality as well as Intensive Care Unit length-of-stay (ICU-LOS) in critically ill patients. We aimed to examine the aforementioned associations by conducting a prospective cohort study in an ICU of a Singapore tertiary hospital. Between August 2015 and October 2016, all adult patients with ≥24 h of ICU-LOS were included. The 7-point Subjective Global Assessment (7-point SGA) was used to determine patients’ nutritional status within 48 hours of ICU admission. Multivariate analyses were conducted in two ways: 1) presence versus absence of malnutrition, and 2) dose-dependent association for each 1-point decrease in the 7-point SGA. There were 439 patients of which 28.0% were malnourished, and 29.6% died before hospital discharge. Malnutrition was associated with an increased risk of hospital mortality [adjusted-RR 1.39 (95%CI: 1.10–1.76)], and this risk increased with a greater degree of malnutrition [adjusted-RR 1.09 (95%CI: 1.01–1.18) for each 1-point decrease in the 7-point SGA]. No significant association was found between malnutrition and ICU-LOS. Conclusion: There was a clear association between malnutrition and higher hospital mortality in critically ill patients. The association between malnutrition and ICU-LOS could not be replicated and hence requires further evaluation.

Background: Nutrient supplements are widely used for type 2 diabetes (T2D) yet evidence-based guidance for clinicians is lacking. Methods: We searched the four electronic databases from November 2015–December 2021. The most recent, most comprehensive, high-ranked systematic reviews, meta-analyses and/or umbrella reviews of randomised controlled trials in adults with T2D were included. Data were extracted on study characteristics, aggregate outcome measures per group (glycemic control, measures of insulin sensitivity and secretion), adverse events, and GRADE assessments. Quality was assessed using AMSTAR-2. Results: Twelve meta-analyses and one umbrella review were included. There was very low certainty evidence that chromium, Vitamin C and omega-3 polyunsaturated fatty acids (-3 PUFAs) were superior to placebo for the primary outcome of HbA1c (MD -0.54%, -0.54% and ES -0.27 respectively). Probiotics were superior to placebo for HbA1c (WMD -0.43%). There was very low certainty evidence that Vitamin D was superior to placebo for lowering HbA1c in trials of <6 months (MD -0.17%). Magnesium, zinc, Vitamin C, probiotics and polyphenols were superior to placebo for FBG. Vitamin D was superior to placebo for insulin resistance. Data on safety was limited. Conclusions: Future research should identify who may benefit from nutrient supplementation, safety, and optimal regimens and formulations.

SARS-CoV-2 is a novel betacoronavirus and the aetiological agent of the current COVID-19 outbreak that originated in Hubei Province, China. While polymerase chain reaction is the front-line tool for SARS-CoV-2 surveillance, application of amplification-free and culture-free methods for isolation of SARS-CoV-2 RNA, partnered with next-generation sequencing, would provide a useful tool for both surveillance and research of SARS-CoV-2. We here release into the public domain a set of bait capture hybridization probe sequences for enrichment of SARS-CoV-2 RNA from complex biological samples. These probe sequences have been designed using rigorous bioinformatics methods to provide sensitivity, accuracy, and minimal off-target hybridization. Probe design was based on existing, validated approaches for detecting antimicrobial resistance genes in complex samples and it is our hope that this SARS-CoV-2 bait capture platform, once validated by those with samples in hand, will be of aid in combating the current outbreak.

Oxidative stress is increasingly implicated in male secondary infertility, where the seminal plasma altered proteome composition plays a critical role. This study aims to explore proteomic changes in the seminal plasma of fertile individuals with oxidative stress and secondary infertility patients, hypothesizing oxidative stress as a key factor in secondary infertility. Pooled semen samples from both groups underwent quantitative proteomics analysis using advanced mass spectrometry, with subsequent bioinformatic analysis using tools like DAVID, STRING, and IPA for identifying differentially expressed proteins (DEPs). The study identified 377 DEPs in the secondary infertile group and 523 DEPs in healthy controls, revealing seven mutual pathways including acute phase response signaling and free radical scavenging. Significant alterations were noted in proteins like C3 and SERPINA3, associated with sperm function and fertility. The findings suggest that oxidative stress-induced proteomic alterations in seminal plasma are linked to secondary infertility, highlighting potential biomarkers and therapeutic targets. This research underscores the importance of understanding the interplay between oxidative stress and seminal plasma proteins, potentially guiding personalized treatment strategies to improve fertility outcomes in affected individuals.