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Introduction and objectivesIntra-articular corticosteroid injections are standard of care for managing joint pain secondary to osteoarthritis or rheumatoid arthritis but are rarely used in haemophilic arthropathy. We have introduced and evaluated the efficacy and safety of ultrasound-guided corticosteroid injections for pain relief in patients with haemophilic arthropathy.Patients and methodsUltrasound-guided intra-articular injections performed on haemophilia patients at UCSD between March 2012 and January 2016 were analysed. Needle placement and injection (40 mg triamcinolone; 3-5 mL lidocaine) were performed with musculoskeletal ultrasound and Power Doppler. Analysis included patient demographics, joint-specific parameters such as tissue hypervascularity and effusions, pain relief, and procedure-associated complications.ResultsForty-five injections (14 ankles, 13 elbows, 18 knees) were administered in 25 patients. Advanced arthropathy with hypervascularity and/or effusions was present in 91% and 61% of joints, respectively. Ninety-one per cent of injections resulted in pain relief which was significant in 84% (>30% reduction). Median pain score was reduced from 7 of 10 to 1 of 10 (P < 0.001), usually within 24 h. Median duration of pain relief was 8 weeks (range 1-16 weeks). Haemophilia B patients experienced longer periods of relief, and high Pettersson scores were associated with shorter duration of relief. There were no procedure-associated complications. Repeat ultrasound of eight joints within 4 weeks of injection demonstrated nearly complete resolution of hypervascularity.ConclusionsPoint-of-care ultrasound enabled intra-articular corticosteroid injections that provided highly effective, safe, and relatively long-lasting pain relief in haemophilic arthropathy. This approach should be used to improve pain management in haemophilic arthropathy.

This study investigates public attitudes towards the use of human excretion-based fertiliser (HEBF) in agriculture. Focusing on England and Japan, countries with contrasting histories of nightsoil use, we conducted representative surveys to understand public acceptance and sex-based differences in attitudes. Our findings reveal significant cultural and sex-based disparities in the willingness to utilize HEBF. The Japanese are more accepting of using HEBF for food production, with fewer health concerns, compared to the English. However, English respondents are more open to using HEBF in public parks. The study emphasises the need for further research on societal perceptions and highlights the importance of cultural context in adopting sustainable practices like HEBF in agriculture.

Introduction Epilepsy surgery is the only curative treatment for patients with drug-resistant focal epilepsy. Stereoelectroencephalography (SEEG) is the gold standard to delineate the seizure-onset zone (SOZ). However, up to 40% of patients are subsequently not operated as no focal non-eloquent SOZ can be identified. The 5-SENSE Score is a 5-point score to predict whether a focal SOZ is likely to be identified by SEEG. This study aims to validate the 5-SENSE Score, improve score performance by incorporating auxiliary diagnostic methods and evaluate its concordance with expert decisions.Methods and analysis Non-interventional, observational, multicentre, prospective study including 200 patients with drug-resistant epilepsy aged ≥15 years undergoing SEEG for identification of a focal SOZ and 200 controls at 22 epilepsy surgery centres worldwide. The primary objective is to assess the diagnostic accuracy and generalisability of the 5-SENSE in predicting focality in SEEG in a prospective cohort. Secondary objectives are to optimise score performance by incorporating auxiliary diagnostic methods and to analyse concordance of the 5-SENSE Score with the expert decisions made in the multidisciplinary team discussion.Ethics and dissemination Prospective multicentre validation of the 5-SENSE score may lead to its implementation into clinical practice to assist clinicians in the difficult decision of whether to proceed with implantation. This study will be conducted in accordance with the Tri-Council Policy Statement: Ethical Conduct for Research Involving Humans (2014). We plan to publish the study results in a peer-reviewed full-length original article and present its findings at scientific conferences.Trial registration number NCT06138808.

BACKGROUND: The HEART score uses elements from patient History, Electrocardiogram, Age, Risk Factors, and Troponin to obtain a risk score on a 0- to 10-point scale for predicting acute coronary syndromes (ACS). This investigation seeks to improve on the HEART score by proposing the HEARTS(3) score, which uses likelihood ratio analysis to give appropriate weight to the individual elements of the HEART score as well as incorporating 3 additional 'S' variables: Sex, Serial 2-hour electrocardiogram, and Serial 2-hour delta troponin during the initial emergency department valuation. METHODS: This is a retrospective analysis of a prospectively acquired database consisting of 2148 consecutive patients with non-ST-segment elevation chest pain. Interval analysis of likelihood ratios was performed to determine appropriate weighting of the individual elements of the HEART(3) score. Primary outcomes were 30-day ACS and myocardial infarction. RESULTS: There were 315 patients with 30-day ACS and 1833 patients without ACS. Likelihood ratio analysis revealed significant discrepancies in weight of the 5 individual elements shared by the HEART and HEARTS(3) score. The HEARTS(3) score outperformed the HEART score as determined by comparison of areas under the receiver operating characteristic curve for myocardial infarction (0.958 vs 0.825; 95% confidence interval difference in areas, 0.105-0.161) and for 30-day ACS (0.901 vs 0.813; 95% confidence interval difference in areas, 0.064-0.110). CONCLUSION: The HEARTS(3) score reliably risk stratifies patients with chest pain for 30-day ACS. Prospective studies need to be performed to determine if implementation of this score as a decision support tool can guide treatment and disposition decisions in the management of patients with chest pain. [ABSTRACT FROM AUTHOR]

The pharmacokinetics and pharmacodynamics of enoxaparin were studied in healthy volunteers and hemodialysis and peritoneal dialysis subjects. Antifactor Xa activity estimated the pharmacokinetics, whereas thrombin generation time (TGT) estimated the pharmacodynamics. Enoxaparin 1 mg/kg was given subcutaneously to all subjects. Antifactor Xa A(max) and AUC(0-12) were similar between groups, but the TGT(max) was significantly greater in the dialysis groups (P = .001). The thrombin generation time remained significantly more prolonged throughout the 12-hour study period, and there was a trend toward greater TGT AUEC(0-12) for both dialysis groups (P = .07). Patients receiving hemodialysis had greater sensitivity to enoxaparin compared to the other groups. These results suggest that in dialysis patients, there may be accumulation of active heparin metabolites that are undetected by the antifactor Xa assay. Therefore, these subjects exhibit greater thrombin generation time prolongation despite similar antifactor Xa exposure. Further large-scale studies are needed to corroborate the results of this exploratory pilot study. [ABSTRACT FROM AUTHOR]

In the visual perception literature, the recognition of faces has often been contrasted with that of non-face objects, in terms of differences with regard to the role of parts, part relations and holistic processing. However, recent evidence from developmental studies has begun to blur this sharp distinction. We review evidence for a protracted development of object recognition that is reminiscent of the well-documented slow maturation observed for faces. The prolonged development manifests itself in a retarded processing of metric part relations as opposed to that of individual parts and offers surprising parallels to developmental accounts of face recognition, even though the interpretation of the data is less clear with regard to holistic processing. We conclude that such results might indicate functional commonalities between the mechanisms underlying the recognition of faces and non-face objects, which are modulated by different task requirements in the two stimulus domains.

The spatial pattern across the continental United States of the interannual variance of warm-season water-dependent evapotranspiration, a pattern of relevance to land-atmosphere feedback, cannot be measured directly. Alternative and indirect approaches to estimating the pattern, however, do exist, and given the uncertainty of each, we use several such approaches here. We first quantify the water-dependent evapotranspiration variance pattern inherent in two derived evapotranspiration datasets available from the literature. We then search for the pattern in proxy geophysical variables (air temperature, streamflow, and NDVI) known to have strong ties to evapotranspiration. The variances inherent in all of the different (and mostly independent) data sources show some differences but are generally strongly consistent – they all show a large variance signal down the center of the U.S., with lower variances toward the east and (for the most part) toward the west. The robustness of the pattern across the datasets suggests that it indeed represents the pattern operating in nature. Using Budyko’s hydroclimatic framework, we show that the pattern can largely be explained by the relative strength of water and energy controls on evapotranspiration across the continent.

Biomass crops are perceived as a feasible means to substitute sizeable amounts of fossil fuel in the future. A prospect of CO2 reduction (resp. CO2 neutrality) is credited to biomass fuels, and thus a potential contribution to mitigate climate change. Short rotation coppices (SRC) with fast growing poplar and willow trees are an option for producing high yields of woody biomass, which is suitable for both energetic and material use. One negative effect that comes along with the establishment of SRC may be a decrease in groundwater recharge, because high rates of transpiration and interception are anticipated. Therefore, it is important to measure, analyse, and model the effects of SRC-planting on landscape water budgets. To analyse the effects on the water budget a poplar SRC plot was studied by measuring hydrological parameters to be used in the hydrological model WaSim. Results reveal very low or even missing ground water recharge for SRC compared to agricultural land use or grassland, especially succeeding dry years. However, this strong effect on plot level is moderated on the larger spatial scale of catchment level, for which the modelling was also performed. In addition to water, nutrient fluxes and budgets were studied. Nitrogen is still a crucial issue in today's agriculture. Intensive fertilization or increased applications of manure from concentrated livestock breeding are often leading to high loads of nitrate leaching, or enhanced N2O emissions to the atmosphere on arable crop fields. SRC or agroforestry systems (AF) on former crop land may offer an option to decrease such N losses, while simultaneously producing woody biomass. This is mainly due to the generally smaller N requirements of woody vegetation, which usually entail no need for any fertilization. The trees supply deep and permanent rooting systems, which can be regarded as a safety net to prevent nutrient leaching. Thus, SRC altogether can help to diminish N eutrophication.

Species with similar resource requirements are commonly assumed to competitively exclude each other, unless they differentiate their ecological niches. Hence, parasitoid wasps that use the same host species need to find some way to avoid competition. The aim of this study was to identify the role of volatile cues from oilseed rape plants and the larval host in niche separation between three coexisting parasitoid species. We examined how Phradis interstitialis, Phradis morionellus and Tersilochus heterocerus, sympatric parasitoids of Brassicogethes aeneus, differ in their abundances, distribution on buds and flowers, and oviposition behavior in the field. Furthermore, we tested their preferences for odours from uninfested and infested oilseed rape plants in the bud and flowering stage, and their preferences for odours from three developmental stages of pollen beetle larvae in a two-choice olfactometer bioassay.P. interstitialis was active in the field early in the season, preferred odours of infested buds versus uninfested, and oviposited into buds which contained only pollen beetle eggs, while P. morionellus was active late in the season, preferred odours of infested buds as well as odours of infested flowers over uninfested, and oviposited into buds which contained only larvae. T. heterocerus was active throughout the season, and preferred odours of infested flowers over uninfested. Neither Phradis species were attracted to larval odours, whereas T. heterocerus was attracted to odours from first-instar pollen beetle larvae both in the absence of plant odours, and when presented simultaneously with uninfested plant odour.This suggests that the two Phradis species are separated on a temporal scale and that they parasitize different host stages, while the larval parasitoids P. morionellus and T. heterocerus are separated by choice of microhabitat. The former oviposits into larvae in buds, and the latter in flowers.

Assigning political actors positions in ideological space is a task of key importance to political scientists. In this paper we compare estimates obtained using the automated Wordscores and Wordfish techniques, along with estimates from voters and the Comparative Manifesto Project (CMP), against expert placements. We estimate the positions of 254 manifestos across 33 elections in Germany and Denmark, two cases with very different textual data available. We find that Wordscores approximately replicates the CMP, voter, and expert assessments of party positions in both cases, whereas Wordfish replicates the positions in the German manifestos only. The results demonstrate that automated methods can produce valid estimates of party positions, but also that the appropriateness of each method hinges on the quality of the textual data. Additional analyses suggest that Wordfish requires both longer texts and a more ideologically charged vocabulary in order to produce estimates comparable to Wordscores. The paper contributes to the literature on automated content analysis by providing a comprehensive test of convergent validation, in terms of both number of cases analyzed and number of validation measures.

Phytohormone salicylic acid (SA) is a crucial component of plant induced defense against biotrophic pathogens. Although the key players of SA pathway are known, there are still gaps in our understanding of molecular mechanism and regulation of particular steps. In our previous research we showed in Arabidopsis suspension cells that n-butanol, which specifically modulates phospholipase D activity, significantly supresses transcription of pathogenesis related (PR1) gene generally accepted as SA pathway marker. In the presented study, we have investigated the site of n-butanol action in SA pathway. We were able to show in Arabidopsis plants treated with SA that n-butanol inhibits the transcription of defense genes (PR-1, WRKY38). Fluorescence microscopy of Arabidopsis thaliana mutants expressing 35S::NPR1-GFP (nonexpressor pathogenesis related 1) revealed significantly decreased nuclear localization of NPR1 in the presence of n-butanol. On the other hand, n-butanol did not affect nuclear localization of NPR1 in 35S::npr1C82A-GFP and 35S::npr1C216A-GFP mutants constitutively expressing NPR1 monomers. We also observed decreasing effect of n-butanol on ROS production, another important factor in plant response to pathogen attack.Mass spectrometric analysis of plant extracts showed that n-butanol significantly changes metabolic fingerprinting while t-butanol had no effect. We found groups of plant metabolites, influenced differently by SA and n-butanol treatment and we proposed several metabolites as markers for n-butanol action.

Objective. Approximately 5% of women suffer from recurrent vulvovaginal candidiasis (RVVC). It has been hypothesized that genetic factors play an important role in the susceptibility to RVVC. The aim of this study was to assess the effect of genetic variants of genes encoding for Pattern Recognition Receptors (PRRs) on susceptibility to RVVC.Study design. For the study, 119 RVVC patients and 263 healthy controls were recruited. Prevalence of polymorphisms in five PRRs involved in recognition of Candida were investigated in patients and controls. In silico and functional studies were performed to assess their functional effects. Results. Single nucleotide polymorphisms (SNPs) in TLR1, TLR4, CLEC7A and CARD9 did not affect the susceptibility to RVVC. In contrast, a non-synonymous polymorphism in TLR2 (rs5743704, Pro631His) increased the susceptibility to RVVC almost 3-fold. Furthermore, the TLR2 rs5743704 SNP had deleterious effects on protein function as assessed by in-silico analysis, and in-vitro functional assays suggested that it reduces production of IL-17 and IFN upon stimulation of peripheral blood mononuclear cells with C. albicans. No effects were observed on serum MBL concentrations.Conclusion. Genetic variation in TLR2 may significantly enhance susceptibility to RVVC by modulating host defense mechanisms against Candida. Additional studies are warranted to assess systematically the role of host genetic variation for susceptibility to RVVC.

Asthma is characterized by airway inflammation. Inflammation is associated with oxidant stress. Airway epithelial cells are shielded from this stress by a thin layer of lung lining fluid (LLF) which contains an abundance of the antioxidant glutathione. LLF glutathione metabolism is regulated by γ-glutamyl transferase (GGT). Loss of LLF GGT activity in the mutant GGTenu1 mouse causes an increase in baseline LLF glutathione content which is magnified in an IL-13 model of allergic airway inflammation and protective against asthma. Normal mice are susceptible to asthma in this model but can be protected with acivicin, a GGT inhibitor. GGT is a target to treat asthma but acivicin toxicity limits clinical use. GGsTop is a novel GGT inhibitor. GGsTop inhibits LLF GGT activity only when delivered through the airway. In the IL-13 model, mice treated with IL-13 and GGsTop exhibit a lung inflammatory response similar to that of mice treated with IL-13 alone. But mice treated with IL-13 and GGsTop show attenuation of methacholine-stimulated airway hyper-reactivity, inhibition of Muc5ac and Muc5b gene induction, decreased airway epithelial cell mucous accumulation and a 4-fold increase in LLF glutathione content compared to mice treated with IL-13 alone. Mice treated with GGsTop alone are no different from that of mice treated with saline alone, and show no signs of toxicity. GGsTop could represent a valuable pharmacological tool to inhibit LLF GGT activity in pulmonary disease models. The associated increase in LLF glutathione can protect lung airway epithelial cells against oxidant injury associated with inflammation in asthma.

Methanogenic degradation of crude oil in subsurface sediments occurs slowly, but without the need for exogenous electron acceptors, is sustained for long periods and has enormous economic and environmental consequences. Here we show that volatile hydrocarbons are inhibitory to methanogenic oil biodegradation by comparing degradation of an artificially weathered crude oil with volatile hydrocarbons removed, with the same oil that was not weathered. Volatile hydrocarbons (nC5-nC10, methylcyclohexane, benzene, toluene and xylenes) were quantified in the headspace of microcosms. Aliphatic (n-alkanes nC12-nC34) and aromatic hydrocarbons (4-methylbiphenyl, 3-methylbiphenyl, 2-methylnaphthalene, 1-methylnaphthalene) were quantified in the total hydrocarbon fraction extracted from the microcosms. 16S rRNA genes from key microorganisms known to play an important role in methanogenic alkane degradation (Smithella and Methanomicrobiales) were quantified by quantitative PCR. Methane production from degradation of weathered oil in microcosms was rapid (1.1 ± 0.1 µmol CH4/g sediment/day) with stoichiometric yields consistent with degradation of heavier n-alkanes (nC12-nC34). For non-weathered oil, degradation rates in microcosms were significantly lower (0.4 ± 0.3 µmol CH4/g sediment/day). This indicated that volatile hydrocarbons present in the non-weathered oil inhibit, but do not completely halt, methanogenic alkane biodegradation. These findings are significant with respect to rates of biodegradation of crude oils with abundant volatile hydrocarbons in anoxic, sulphate-depleted subsurface environments, such as contaminated marine sediments which have been entrained below the sulfate-reduction zone, as well as crude oil biodegradation in petroleum reservoirs and contaminated aquifers.

Generating the raw data for a de novo genome assembly project for a target eukaryotic species is relatively easy. This democratisation of access to large-scale data has allowed many research teams to plan to assemble the genomes of non-model organisms. These new genome targets are very different from the traditional, inbred, laboratory reared model organisms. They are often small, and cannot be isolated free of their environment - whether ingested food, the surrounding host organism of parasites, or commensal and symbiotic organisms attached to or within the individuals sampled. Preparation of pure DNA originating from a single species can be technically impossible, but assembly of mixed-organism DNA can be difficult, as most genome assemblers perform poorly when faced with multiple genomes in different stoichiometries. This class of problem is common in metagenomic datasets that deliberately try to capture all the genomes present in an environment, but replicon assembly is not often the goal of such programmes. Here we present an approach to extracting from mixed DNA sequence data subsets that correspond to single species' genomes and thus improving genome assembly. We use both numerical (proportion of GC bases and read coverage) and biological (best-matching sequence in annotated databases) indicators to aid partitioning of draft assembly contigs, and the reads that contribute to those contigs, into distinct bins that can then be subjected to rigorous, optimised assembly, through the use of taxon-annotated GC-coverage plots (TAGC plots). We also present Blobsplorer, a tool that aids exploration and selection of subsets from TAGC annotated data. Partitioning the data in this way can rescue poorly assembled genomes, and reveal unexpected symbionts and commensals in eukaryotic genome projects. The TAGC plot pipeline script is available from http://github.com/blaxterlab/blobology, and the Blobsplorer tool from https://github.com/mojones/Blobsplorer.

Abstract Background Invertebrate nervous systems are highly disparate between different taxa. This is reflected in the terminology used to describe them, which is very rich and often confusing. Even very general terms such as 'brain', 'nerve', and 'eye' have been used in various ways in the different animal groups, but no consensus on the exact meaning exists. This impedes our understanding of the architecture of the invertebrate nervous system in general and of evolutionary transformations of nervous system characters between different taxa. Results We provide a glossary of invertebrate neuroanatomical terms with a precise and consistent terminology, taxon-independent and free of homology assumptions. This terminology is intended to form a basis for new morphological descriptions. A total of 47 terms are defined. Each entry consists of a definition, discouraged terms, and a background/comment section. Conclusions The use of our revised neuroanatomical terminology in any new descriptions of the anatomy of invertebrate nervous systems will improve the comparability of this organ system and its substructures between the various taxa, and finally even lead to better and more robust homology hypotheses.

Maintaining a diverse gene pool is important in the captive management of zoo populations, especially in endangered species such as the pink pigeon (Nesoenas mayeri). However, due to the limited number of breeding individuals and relaxed natural selection, the loss of variation and accumulation of harmful variants is inevitable. Inbreeding results in a loss of fitness (i.e., inbreeding depression), principally because related parents are more likely to transmit a copy of the same recessive deleterious genetic variant to their offspring. Genomics-informed captive breeding can manage harmful variants by artificial selection, reducing the genetic load by avoiding the inheritance of two copies of the same harmful variant. To explain this concept in an interactive way to zoo visitors, we developed a sonification game to represent the fitness impacts of harmful variants by detuning notes in a familiar musical melody (i.e., Beethoven's Für Elise). Conceptually, zoo visitors play a game aiming to create the most optimal pink pigeon offspring in terms of inbreeding depression. They select virtual crosses between pink pigeon individuals and listen for the detuning of the melody, which represents the realised load of the resultant offspring. Here we present the sonification algorithm and the results of an online survey to see whether participants could identify the most and least optimal offspring from three potential pink pigeon offspring. Of our 98 respondents, 85 (86.7%) correctly identified the least optimal offspring, 73 (74.5%) correctly identified the most optimal, and 62 (63.3%) identified both the most and least optimal offspring using only the sonification., (© 2024 The Author(s). Zoo Biology published by Wiley Periodicals LLC.)

Phenotypic assays have become an established approach to drug discovery. Greater disease relevance is often achieved through cellular models with increased complexity and more detailed readouts, such as gene expression or advanced imaging. However, the intricate nature and cost of these assays impose limitations on their screening capacity, often restricting screens to well-characterized small compound sets such as chemogenomics libraries. Here, we outline a cheminformatics approach to identify a small set of compounds with likely novel mechanisms of action (MoAs), expanding the MoA search space for throughput limited phenotypic assays. Our approach is based on mining existing large-scale, phenotypic high-throughput screening (HTS) data. It enables the identification of chemotypes that exhibit selectivity across multiple cell-based assays, which are characterized by persistent and broad structure activity relationships (SAR). We validate the effectiveness of our approach in broad cellular profiling assays (Cell Painting, DRUG-seq, and Promotor Signature Profiling) and chemical proteomics experiments. These experiments revealed that the compounds behave similarly to known chemogenetic libraries, but with a notable bias toward novel protein targets. To foster collaboration and advance research in this area, we have curated a public set of such compounds based on the PubChem BioAssay dataset and made it available for use by the scientific community.

Predicting compound activity in assays is a long-standing challenge in drug discovery. Computational models based on compound-induced gene expression signatures from a single profiling assay have shown promise toward predicting compound activity in other, seemingly unrelated, assays. Applications of such models include predicting mechanisms-of-action (MoA) for phenotypic hits, identifying off-target activities, and identifying polypharmacologies. Here, we introduce transcriptomics-to-activity transformer (TAT) models that leverage gene expression profiles observed over compound treatment at multiple concentrations to predict the compound activity in other biochemical or cellular assays. We built TAT models based on gene expression data from a RASL-seq assay to predict the activity of 2692 compounds in 262 dose-response assays. We obtained useful models for 51% of the assays, as determined through a realistic held-out set. Prospectively, we experimentally validated the activity predictions of a TAT model in a malaria inhibition assay. With a 63% hit rate, TAT successfully identified several submicromolar malaria inhibitors. Our results thus demonstrate the potential of transcriptomic responses over compound concentration and the TAT modeling framework as a cost-efficient way to identify the bioactivities of promising compounds across many assays.

The need for prehospital hemostatic dressings that exert an antibacterial effect is of interest for prolonged field care. Here, we consider a series of antibacterial and zeolite formulary treatment approaches applied to a cotton-based dressing. The design of the fabric formulations was based on the hemostatic dressing TACGauze with zeolite Y incorporated as a procoagulant with calcium and pectin to facilitate fiber adherence utilizing silver nanoparticles, and cellulose-crosslinked ascorbic acid to confer antibacterial activity. Infra-red spectra were employed to characterize the chemical modifications on the dressings. Contact angle measurements were employed to document the surface hydrophobicity of the cotton fabric which plays a role in the contact activation of the coagulation cascade. Ammonium Y zeolite-treated dressings initiated fibrin equal to the accepted standard hemorrhage control dressing and showed similar improvement with antibacterial finishes. The antibacterial activity of cotton-based technology utilizing both citrate-linked ascorbate-cellulose conjugate analogs and silver nanoparticle-embedded cotton fibers was observed against Staphylococcus aureus and Klebsiella pneumoniae at a level of 99.99 percent in the AATCC 100 assay. The hydrogen peroxide levels of the ascorbic acid-based fabrics, measured over a time period from zero up to forty-eight hours, were in line with the antibacterial activities.

Human induced pluripotent stem cell (hiPSC)-derived cells can reproduce human-specific pathophysiology, patient-specific vulnerability, and gene-environment interactions in neurological disease. Human in vitro models of neurotrauma therefore have great potential to advance the field. However, this potential cannot be realized until important biomaterials challenges are addressed. Status quo stretch injury models of neurotrauma culture cells on sheets of polydimethylsiloxane (PDMS) that are incompatible with long-term monoculture of hiPSC-derived neurons. Here, we overcame this challenge in an established human in vitro neurotrauma model by replacing PDMS with a highly biocompatible form of polyurethane (PU). This substitution allowed long-term monoculture of hiPSC-derived neurons. It also changed the biomechanics of stretch injury. We quantified these changes experimentally using high-speed videography and digital image correlation. We used finite element modeling to quantify the influence of the culture substrate's thickness, stiffness, and coefficient of friction on membrane stretch and concluded that the coefficient of friction explained most of the observed biomechanical changes. Despite these changes, we demonstrated that the modified model produced a robust, dose-dependent trauma phenotype in hiPSC-derived neuron monocultures. In summary, the introduction of this PU film makes it possible to maintain hiPSC-derived neurons in monoculture for long periods in a human in vitro neurotrauma model. In doing so, it opens new horizons in the field of neurotrauma by enabling the unique experimental paradigms (e.g., isogenic models) associated with hiPSC-derived neurons., Competing Interests: Simon Dixon is an employee of Biomer Technology Ltd., (© Angela Mitevska et al., 2023; Published by Mary Ann Liebert, Inc.)

Does warmth from hydrothermal springs play a vital role in the biology and ecology of abyssal animals? Deep off central California, thousands of octopus ( Muusoctopus robustus ) migrate through cold dark waters to hydrothermal springs near an extinct volcano to mate, nest, and die, forming the largest known aggregation of octopus on Earth. Warmth from the springs plays a key role by raising metabolic rates, speeding embryonic development, and presumably increasing reproductive success; we show that brood times for females are ~1.8 years, far faster than expected for abyssal octopods. Using a high-resolution subsea mapping system, we created landscape-scale maps and image mosaics that reveal 6000 octopus in a 2.5-ha area. Because octopuses die after reproducing, hydrothermal springs indirectly provide a food supplement to the local energy budget. Although localized deep-sea heat sources may be essential to octopuses and other warm-tolerant species, most of these unique and often cryptic habitats remain undiscovered and unexplored.

Recent work showed that active site rather than full-protein-sequence information improves predictive performance in kinase-ligand binding affinity prediction. To refine the notion of an "active site", we here propose and compare multiple definitions. We report significant evidence that our novel definition is superior to previous definitions and better models of ATP-noncompetitive inhibitors. Moreover, we leverage the discontiguity of the active site sequence to motivate novel protein-sequence augmentation strategies and find that combining them further improves performance.

Background: There are many options for glenosphere baseplate fixation commercially available, yet there is little biomechanical evidence supporting one type of fixation over another. In this study, we compared the biomechanical fixation of a reverse total shoulder glenoid baseplate secured with locking or non-locking peripheral screws., Methods: Both a non-augmented mini baseplate with full backing support and an augmented baseplate were testing after implantation in solid rigid polyurethane foam. Each baseplate was implanted with a 30 mm central compression screw and four peripheral screws, either locking or non-locking (15 mm anterior/posterior and 30 mm superior/inferior). A 1 Hz cyclic force of 0-750 N was applied at a 60 o angle for 5000 cycles. Throughout the test, the displacement of the baseplate was measured using a 3D Digital Image Correlation System., Findings: The amount of migration measured in the both the non-augmented and augment cases shows no significant differences between locking and non-locking cases at the final cycle count (non-augment: 5.66 +/- 2.29 μm vs. 3.71 +/- 1.23 μm; p = 0.095, augment: 15.43 +/- 8.49 μm vs. 12.46 +/- 3.24 μm; p = 0.314). Additionally, the amount of micromotion measured for both sample types shows the same lack of significant difference (non-augment: 10.79 +/- 5.22 μm vs. 10.16 +/- 7.61 μm; p = 0.388, augment: 55.03 +/- 10.13 μm vs. 54.84 +/- 10.65 μm; p = 0.968)., Interpretation: The presence of locking versus non-locking peripheral screws does not make a significant difference on the overall stability of a glenoid baseplate, in both a no defect case with a non-augmented baseplate and a bone defect case with an augmented baseplate., (Copyright © 2022. Published by Elsevier Ltd.)

Background: We evaluated radiation oncology residency program directors' attitudes toward discrete palliative care skills in effort to determine which skills should be prioritized in radiation oncology resident training. Design: We identified 93 U.S. radiation oncology residency program directors and sent them a survey through e-mail. The survey assessed views of 27 discrete palliative care skills in eight domains and was adapted from the American Society of Clinical Oncology/American Academy of Hospice and Palliative Medicine Guidance Statement defining high-quality primary palliative care in medical oncology. Using a nine-point scale, respondents rated each skill on three constructs: (1) importance to high-quality cancer care, (2) relevance of the skill to radiation oncology practice, and (3) importance to radiation oncology residency education. Skills were categorized as "Include" (median score ≥7 for all constructs), "Exclude" (median score ≤3 for all constructs), or "Uncertain" (all other skills) using a composite score of all constructs. Results: Twenty-nine program directors (response rate 31%) completed the survey. Of the 27 skills, 100% were rated as highly important to high-quality cancer care, 70% were rated as highly relevant to radiation oncology practice, and 81% were rated as highly important to resident education (median score ≥7). Using the composite score, 70% of skills were categorized as "Include." The domains of Caregiver Support (100%), End-of-Life Care (66%), and Spiritual/Cultural Assessment and Management (33%) had the highest proportions of skills rated as "Uncertain." Conclusions: The surveyed radiation oncology residency program directors generally value palliative care skills within radiation oncology.

The removal of dissolved volatile organic compounds (VOCs) from low-permeability lenses is important to limit back diffusion at sites impacted by dense non-aqueous phase liquids (DNAPLs). In situ thermal treatment (ISTT) technologies have the potential to treat DNAPL-impacted sites by enhancing diffusion from low-permeability lenses during heating. A series of two-dimensional laboratory tank experiments was conducted to investigate heating, gas formation, and trichloroethene (TCE) removal from a clay lens surrounded by sand. Results showed preferential heating of the clay and substantial TCE removal, with post-heating relative concentrations less than 0.06. The extent of TCE removal was not explained by only an increase in the aqueous TCE diffusion coefficient with increased temperature. Modelling estimates based on 1D diffusion from the lens showed that diffusion through both gas and water phases was required to match observations. Gas formation in the interior of the lens was also indicated by measured changes in bulk electrical conductivity of the clay during cool down, with gas saturations estimated to be greater than 0.21 at the end of heating. These estimates were larger than those needed to match the observed removal by diffusion, and suggest that connected gas pathways were created in the lens during heating, but that not all of the gas produced was part of those pathways. These results suggest that ISTT technologies may be effective in removing dissolved VOCs from thin clay lenses, and that gas formation within the clay should be considered when predicting the extent and rate of removal., (Copyright © 2021 Elsevier B.V. All rights reserved.)

Background: The use of sound to represent sequence data-sonification-has great potential as an alternative and complement to visual representation, exploiting features of human psychoacoustic intuitions to convey nuance more effectively. We have created five parameter-mapping sonification algorithms that aim to improve knowledge discovery from protein sequences and small protein multiple sequence alignments. For two of these algorithms, we investigated their effectiveness at conveying information. To do this we focussed on subjective assessments of user experience. This entailed a focus group session and survey research by questionnaire of individuals engaged in bioinformatics research., Results: For single protein sequences, the success of our sonifications for conveying features was supported by both the survey and focus group findings. For protein multiple sequence alignments, there was limited evidence that the sonifications successfully conveyed information. Additional work is required to identify effective algorithms to render multiple sequence alignment sonification useful to researchers. Feedback from both our survey and focus groups suggests future directions for sonification of multiple alignments: animated visualisation indicating the column in the multiple alignment as the sonification progresses, user control of sequence navigation, and customisation of the sound parameters., Conclusions: Sonification approaches undertaken in this work have shown some success in conveying information from protein sequence data. Feedback points out future directions to build on the sonification approaches outlined in this paper. The effectiveness assessment process implemented in this work proved useful, giving detailed feedback and key approaches for improvement based on end-user input. The uptake of similar user experience focussed effectiveness assessments could also help with other areas of bioinformatics, for example in visualisation., (© 2021. The Author(s).)

The current coronavirus pandemic has forced a dramatic shift in the way clinicians practice medicine, including the way we communicate with our patients. The pandemic has both facilitated and challenged serious illness conversations between providers and patients. Furthermore, telemedicine has emerged as a major practice across the globe. Benefits of which include greater involvement of supporting family members while drawbacks involve socioeconomic barriers that limit high quality interactions between provider and patient. This commentary aims to highlight the evolution of communication strategies over this unique time in hopes of promoting reflection and change to improve our communication strategies at the individual and institutional level., Competing Interests: Conflict of interest No authors have a conflict of interest or potential conflicts related to this article. No competing interests to declare., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Introduction: Tissue factor pathway inhibitor (TFPI) is an endogenous protein that inhibits the extrinsic (tissue factor) pathway and negatively regulates thrombin production during coagulation. Inhibiting TFPI may become a useful target for haemophilia drug development to allow greater thrombin generation without use of the intrinsic (contact) pathway., Aims: The in vitro effects of befovacimab, a humanized TFPI neutralizing antibody, were studied in whole blood and plasma samples from patients with severe FVIII deficiency., Methods: Blood and plasma obtained from participants was supplemented in vitro with befovacimab (0.5, 1, 5, 10 and 100 nM) or recombinant factor VIII (rFVIII) 5-, 10- and 40% and analysed using rotational thromboelastometry (ROTEM), thrombin generation assay (TGA) and the dilute prothrombin time (dPT) assay. The in vitro coagulation effects of befovacimab were compared to samples supplemented with rFVIII., Results: Befovacimab induced consistent pro-coagulant responses in ROTEM parameters including reduction in clotting times and increases in α-angle; induced reductions in dPT clotting time; and improvements in TGA parameters (reduced lag time and increased thrombin generation parameters). There was a modest concentration-dependent response generally from 0.5- to 10 nM, after which, the pharmacodynamic effect plateaued through the 100 nM concentration. Befovacimab concentrations of 5 to 10 nM showed pro-coagulant activity comparable to blood samples supplemented with rFVIII 10-40%., Conclusions: Befovacimab has modest dose-response effects from 0.5 to 10 nM with minimal improvement with higher concentrations. In vitro befovacimab blood concentrations of 5 to 10 nM had pro-coagulant effects similar to blood supplemented with rFVIII 10- to 40%., (© 2021 John Wiley & Sons Ltd.)

Background: Glenoid bone loss is commonly encountered in cases of rotator cuff tear arthropathy and can create challenges during reverse shoulder arthroplasty. In this study, we sought to investigate the biomechanical properties of a new treatment option for superior glenoid defect, an augmented reverse total shoulder baseplate., Methods: Three conditions were examined: non-augmented baseplate without defect, non-augmented baseplate with defect, and augmented baseplate with defect. The augmented baseplates included a 30-degree half wedge which also matched the created superior defect. The samples were cyclically loaded at a 60 ° simulated abduction angle to mimic baseplate loosening. The migration and micromotion of the baseplate were measured on the superior edge using a 3D Digital Image Correlation System., Results: The migration measured in the augmented baseplate showed no significant difference when compared to the no defect or defect cases. In terms of micromotion, the augmented baseplate showed values that were between the micromotions reported for the no defect and defect conditions, but not by a statistically significant amount., Conclusion: This study provides biomechanical evidence that augmented baseplates can reduce the amount of micromotion experienced by the RSA construct in the presence of significant superior glenoid bone deficiency, but do not fully restore stability to that of a full contact non-augmented baseplate., Competing Interests: Declaration of Conflicting Interests: The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article., (© The Author(s) 2021.)

The Society for Palliative Radiation Oncology (SPRO) is an international professional group dedicated to advancing the field of palliative radiation oncology by promoting evidence-based palliative radiotherapy and excellence in primary palliative care through research, education, collaboration, and patient advocacy. SPRO held its 7th Annual Meeting on October 28, 2020 over a virtual platform in association with the American Society for Radiation Oncology (ASTRO) 62nd Annual Meeting. Short and long-term goals for the Society were detailed and the accomplishments since SPRO's 6th Annual Meeting were reviewed. New research was presented during a series of two-minute rapid fire educational sessions given by speakers selected to present in the scientific palliative care track at the ASTRO Annual Meeting. Recipients of the Lifetime Service Award and the Rising Star Award were announced and presented. This Meeting Report summarizes the proceedings of the 7th Annual Meeting and describes future directions for SPRO.