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Background: As life expectancy increases, the population of older individuals with coronary artery disease and frailty is growing. We aimed to assess the impact of patient-reported frailty on the treatment and prognosis of elderly early survivors of non-ST-elevation acute coronary syndrome (NSTE-ACS). Methods: Frailty data were obtained from two prospective trials, POPular Age and the POPular Age Registry, which both assessed elderly NSTE-ACS patients. Frailty was assessed one month after admission with the Groningen Frailty Indicator (GFI) and was defined as a GFI-score of 4 or higher. In these early survivors of NSTE-ACS, we assessed differences in treatment and 1-year outcomes between frail and non-frail patients, considering major adverse cardiovascular events (MACE, including cardiovascular mortality, myocardial infarction, and stroke) and major bleeding. Results: The total study population consisted of 2192 NSTE-ACS patients, aged ≥70 years. The GFI-score was available in 1320 patients (79 ± 5 years, 37% women), of whom 712 (54%) were considered frail. Frail patients were at higher risk for MACE than non-frail patients (9.7% vs. 5.1%, adjusted hazard ratio [HR] 1.57, 95% confidence interval [CI] 1.01–2.43, p = 0.04), but not for major bleeding (3.7% vs. 2.8%, adjusted HR 1.23, 95% CI 0.65–2.32, p = 0.53). Cubic spline analysis showed a gradual increase of the risk for clinical outcomes with higher GFI-scores. Conclusions: In elderly NSTE-ACS patients who survived 1-month follow-up, patient-reported frailty was independently associated with a higher risk for 1-year MACE, but not with major bleeding. These findings emphasize the importance of frailty screening for risk stratification in elderly NSTE-ACS patients.

PurposeTo report on cases of unilateral perimacular atrophy after treatment with voretigene neparvovec-rzyl, in the setting of previous contralateral eye treatment with a different viral vector.DesignSingle-center, retrospective chart review.MethodsIn this case series, four patients between the ages of six and 11 years old with RPE65-related retinopathy were treated unilaterally with rAAV2-CB-hRPE65 as part of a gene augmentation clinical trial (NCT00749957). Six to 10 years later the contralateral eyes were treated with the Food and Drug Administration-approved drug, voretigene neparvovec-rzyl. Best-corrected visual acuity (BCVA), fundus photos, ocular coherence tomography, two-color dark-adapted perimetry, full field stimulus threshold testing (FST), and location of subretinal bleb and chorioretinal atrophy were evaluated.ResultsThree out of four patients showed unilateral perimacular atrophy after treatment with voretigene, ranging from five to 22 months after treatment. Areas of robust visual field improvement were followed by areas of chorioretinal atrophy. Despite perimacular changes, BCVA, FST, and subjective improvements in vision and nyctalopia were maintained. Perimacular atrophy was not observed in the first eye treated with the previous viral vector.ConclusionsWe observed areas of robust visual field improvement followed by perimacular atrophy in voretigene treated eyes, as compared to the initially treated contralateral eyes.Translational relevanceCaution is advised when using two different viral vectors between eyes in gene therapy. This may become an important issue in the future with increasing gene therapy clinical trials for inherited retinal dystrophies.

Microplastics (<5mm), are pervasive in Earth’s environments, and rivers are a major transport pathway. Microplastic detection methods that rely on counting individual particles are time consuming and require laborious field collection, inhibiting real-time insights over large spatial extents, which are needed in order to better understand the issue. Satellite remote sensing has been used to estimate water quality in rivers with relatively high spatial and temporal coverage. Finding a correlation between water quality and microplastics could allow us to estimate microplastics in rivers via satellite imagery using water quality as a proxy. Though a handful of these assessments have been done, a wide-variety of study sites are needed to form a coherent model. We focused our study in the New River near Blacksburg, VA, and collected weekly water quality measurements and surface-water microplastic samples. We combined these in situ measurements with cotemporal remotely-sensed water quality index observations from Sentinel-2 to develop a model estimating microplastic concentration. We validated the model using in-situ spectrometry and water quality measurements. By providing more observations than what can be done with in situ sampling alone, we can improve large-scale microplastic analyses and modeling leading to better assessments of mismanaged plastic waste in Earth’s rivers.

Microplastics (<5mm), are pervasive in Earth’s environments, and rivers are a major transport pathway. Microplastic detection methods that rely on counting individual particles are time consuming and require laborious field collection, inhibiting real-time insights over large spatial extents, which are needed in order to better understand the issue. Satellite remote sensing has been used to estimate water quality in rivers with relatively high spatial and temporal coverage. Finding a correlation between water quality and microplastics could allow us to estimate microplastics in rivers via satellite imagery using water quality as a proxy. Though a handful of these assessments have been done, a wide-variety of study sites are needed to form a coherent model. We focused our study in the New River near Blacksburg, VA, and collected weekly water quality measurements and surface-water microplastic samples. We combined these in situ measurements with cotemporal remotely-sensed water quality index observations from Sentinel-2 to develop a model estimating microplastic concentration. We validated the model using in-situ spectrometry and water quality measurements. By providing more observations than what can be done with in situ sampling alone, we can improve large-scale microplastic analyses and modeling leading to better assessments of mismanaged plastic waste in Earth’s rivers.

Inter-individual differences in the gut microbiome are linked to alterations in inflammation and blood-brain barrier permeability, which may increase the risk of depression in people with HIV (PWH). The microbiome profile of blood, which is considered by many to be typically sterile, remains largely unexplored. We aimed to characterize the blood plasma microbiome composition and assess its association with major depressive disorder (MDD) in PWH and people without HIV (PWoH). In this cross-sectional, observational cohort, we used shallow-shotgun metagenomic sequencing to characterize the plasma microbiome of 151 participants (84 PWH and 67 PWoH), all of whom underwent a comprehensive neuropsychiatric assessment. The microbial composition did not differ between PWH and PWoH or between participants with MDD and those without it. Using the songbird model, we computed the log ratio of the highest and lowest 30% of the ranked classes associated with HIV and MDD. We found that HIV infection and lifetime MDD were enriched in a set of differentially abundant inflammatory classes, such as Flavobacteria and Nitrospira. Our results suggest that the circulating plasma microbiome may increase the risk of MDD related to dysbiosis-induced inflammation in PWH. If confirmed, these findings may indicate new biological mechanisms that could be targeted to improve treatment of MDD in PWH.

Tidal flooding is increasingly common in low-lying coastal regions as sea levels rise. This type of flooding can occur on sunny days with no rainfall and may transport street-associated debris, such as microplastics (MPs) including tire wear particles (TWPs), to coastal systems. This research aimed to quantify MP abundance in tidal floodwater and investigate their fate. Three locations around Charleston, SC (USA) were sampled during 12 tidal floods, and their adjacent tidal creeks were sampled before and after 5 floods. Floodwater contained an average of 342 ± 60 MP/L. Most MPs in floodwater were low-density TWP (86.5 %). MP abundance in tidal creek surface water following flooding did not change, suggesting that MPs were not immediately transferred to coastal waterways but deposited in adjacent marsh sediment. Elucidating transport routes of MPs in coastal environments is critical to understanding and preventing this type of contamination in the face of a changing climate.

Using Commercial Off-The-Shelf (COTS) Operational Amplifiers (OpAmps) and Complementary Metal-Oxide Semiconductor (CMOS) transistors, we present a demonstration of the Q-Pix front-end architecture, a novel readout solution for kiloton-scale Liquid Argon Time Projection Chamber (LArTPC) detectors. The Q-Pix scheme employs a Charge-Integrate/Reset process based on the Least Action principle, enabling pixel-scale self-triggering charge collection and processing, minimizing energy consumption, and maximizing data compression. We examine the architecture's sensitivity, linearity, noise, and other features at the circuit board level and draw comparisons to SPICE simulations. Furthermore, we highlight the resemblance between the Q-Pix front-end and Sigma-Delta modulator, emphasizing that digital data processing techniques for Sigma-Delta can be directly applied to Q-Pix, resulting in enhanced signal-to-noise performance. These insights will inform the development of Q-Pix front-end designs in integrated circuits (IC) and guide data collection and processing for future large-scale LArTPC detectors in neutrino physics and other high-energy physics experiments.

We present the results of a size and structural analysis of 1395 galaxies at $0.5 \leq z \lesssim 8$ with stellar masses $\log \left(M_* / M_{\odot}\right)$ $>$ 9.5 within the JWST Public CEERS field that overlaps with the HST CANDELS EGS observations. We use GALFIT to fit single S\'ersic models to the rest-frame optical profile of our galaxies, which is a mass-selected sample complete to our redshift and mass limit. Our primary result is that at fixed rest-frame wavelength and stellar mass, galaxies get progressively smaller, evolving as $\sim (1+z)^{-0.71\pm0.19}$ up to $z \sim 8$. We discover that the vast majority of massive galaxies at high redshifts have low S\'ersic indices, thus do not contain steep, concentrated light profiles. Additionally, we explore the evolution of the size-stellar mass relationship, finding a correlation such that more massive systems are larger up to $z \sim 3$. This relationship breaks down at $z > 3$, where we find that galaxies are of similar sizes, regardless of their star formation rates and S\'ersic index, varying little with mass. We show that galaxies are more compact at redder wavelengths, independent of sSFR or stellar mass up to $z \sim 3$. We demonstrate the size evolution of galaxies continues up to $z \sim 8$, showing that the process or causes for this evolution is active at early times. We discuss these results in terms of ideas behind galaxy formation and evolution at early epochs, such as their importance in tracing processes driving size evolution, including minor mergers and AGN activity., Comment: Submitted to MNRAS

We present an early analysis on the search for high redshift galaxies using the deepest public JWST imaging to date, the NGDEEP field. This data consists of 6-band NIRCam imaging on the Hubble Ultra Deep Field-Par2, covering a total area of 6.3 arcmin$^{2}$. Based on our initial reduction of the first half of this survey, we reach 5$\sigma$ depths up to mag = 29.5--29.9 between $1-5$ um. Such depths present an unprecedented opportunity to begin exploring the early Universe with JWST. As such, we find high redshift galaxies in this field by examining the spectral energy distribution of these systems and present 18 new $z > 8$ systems identified using two different photometric redshift codes: LePhare and EAZY, combined with other significance criteria. The highest redshift object in our sample is at $z=15.57^{+0.39}_{-0.38}$, which has a blue beta slope of $\beta=-3.25^{+0.41}_{-0.46}$ and a very low inferred stellar mass of $M_{*} = 10^{7.39}$ M_0,. We also discover a series of faint, low-mass dwarf galaxies with $M_{*} < 10^{8.5}$ M_0 at $z \sim 9$ that have blue colors and UV slopes. The structure of these galaxies is such that they all have very flat surface brightness profiles and small sizes $< 1 \ \mathrm{kpc}$. We also compare our results to theory, finding no significant disagreement with some CDM based models.The discovery of these objects, most of which are low luminosity and inferred stellar mass, demonstrates the power of probing continuously deeper into the Universe, pointing the way to deeper, or similar depth but wider area, surveys and demonstrate the critical need for JWST deep fields to explore this aspect of the early Universe., Comment: ApJL submitted. Added acknowledgements and slight change in title. Mosaics of our NGDEEP reductions are available here: tinyurl.com/yckcfnxu

Flash nanoprecipitation (FNP) is a turbulent mixing process capable of reproducibly producing polymer nanoparticles loaded with active pharmaceutical ingredients (APIs). The nanoparticles produced with this method consist of a hydrophobic core surrounded by a hydrophilic corona. FNP produces nanoparticles with very high loading levels of nonionic hydrophobic APIs. However, hydrophobic compounds with ionizable groups are not as efficiently incorporated. To overcome this, ion pairing agents (IPs) can be incorporated into the FNP formulation to produce highly hydrophobic drug salts that efficiently precipitate during mixing. We demonstrate the encapsulation of the PI3K inhibitor, LY294002, within poly(ethylene glycol)-b-poly(D,L lactic acid) nanoparticles. We investigated how incorporating two hydrophobic IPs (palmitic acid (PA) and hexadecylphosphonic acid (HDPA)) during the FNP process affected the LY294002 loading and size of the resulting nanoparticles. The effect of organic solvent choice on the synthesis process was also examined. While the presence of either hydrophobic IP effectively increased the encapsulation of LY294002 during FNP, HDPA resulted in well-defined colloidally stable particles, while the PA resulted in ill-defined aggregates. The incorporation of hydrophobic IPs with FNP opens the door for the intravenous administration of APIs that were previously deemed unusable due to their hydrophobic nature.

Flash nanoprecipitation (FNP) is a turbulent mixing process capable of reproducibly producing polymer nanoparticles loaded with active pharmaceutical ingredients (APIs). The nanoparticles produced with this method consist of a hydrophobic core surrounded by a hydrophilic corona. FNP produces nanoparticles with very high loading levels of nonionic hydrophobic APIs. However, hydrophobic compounds with ionizable groups are not as efficiently incorporated. To overcome this, ion pairing agents (IPs) can be incorporated into the FNP formulation to produce highly hydrophobic drug salts that efficiently precipitate during mixing. We demonstrate the encapsulation of the PI3K inhibitor, LY294002, within poly(ethylene glycol)-b-poly(D,L lactic acid) nanoparticles. We investigated how incorporating two hydrophobic IPs (palmitic acid (PA) and hexadecylphosphonic acid (HDPA)) during the FNP process affected the LY294002 loading and size of the resulting nanoparticles. The effect of organic solvent choice on the synthesis process was also examined. While the presence of either hydrophobic IP effectively increased the encapsulation of LY294002 during FNP, HDPA resulted in well-defined colloidally stable particles, while the PA resulted in ill-defined aggregates. The incorporation of hydrophobic IPs with FNP opens the door for the intravenous administration of APIs that were previously deemed unusable due to their hydrophobic nature.

Atypical Usher syndrome (USH) is poorly defined with a broad clinical spectrum. Here, we characterize the clinical phenotype of disease caused by variants in CEP78, CEP250, ARSG, and ABHD12.Chart review evaluating demographic, clinical, imaging, and genetic findings of 19 patients from 18 families with a clinical diagnosis of retinal disease and confirmed disease-causing variants in CEP78, CEP250, ARSG, or ABHD12.CEP78-related disease included sensorineural hearing loss (SNHL) in 6/7 patients and demonstrated a broad phenotypic spectrum including: vascular attenuation, pallor of the optic disc, intraretinal pigment, retinal pigment epithelium mottling, areas of mid-peripheral hypo-autofluorescence, outer retinal atrophy, mild pigmentary changes in the macula, foveal hypo-autofluorescence, and granularity of the ellipsoid zone. Nonsense and frameshift variants in CEP250 showed mild retinal disease with progressive, non-congenital SNHL. ARSG variants resulted in a characteristic pericentral pattern of hypo-autofluorescence with one patient reporting non-congenital SNHL. ABHD12-related disease showed rod-cone dystrophy with macular involvement, early and severe decreased best corrected visual acuity, and non-congenital SNHL ranging from unreported to severe.This study serves to expand the clinical phenotypes of atypical USH. Given the variable findings, atypical USH should be considered in patients with peripheral and macular retinal disease even without the typical RP phenotype especially when SNHL is noted. Additionally, genetic screening may be useful in patients who have clinical symptoms and retinal findings even in the absence of known SNHL given the variability of atypical USH.

Rapid and repeated photon cycling has enabled precision metrology and the development of quantum information systems using a variety of atoms and simple molecules. Extending optical cycling to structurally complex molecules would provide new capabilities in these areas, as well as in ultracold chemistry. Increased molecular complexity, however, makes realizing closed optical transitions more difficult. Building on the already established strong optical cycling of diatomic, linear triatomic, and symmetric top molecules, recent theoretical and experimental work has indicated that cycling will be extendable to phenol containing molecules, as well as other asymmetric species. The paradigm for these systems is the use of an optical cycling center bonded to a molecular ligand. Theory has suggested that cycling may be extended to even larger ligands, like naphthalene, pyrene and coronene. Here, we study the optical excitation and vibrational branching of the molecules CaO-2-naphthyl, SrO-2-naphthyl and CaO-1-naphthyl and find only weak decay to excited vibrational states, indicating a promising path to full quantum control and laser cooling of large arene-based molecules.

Herein, we report the use of sterically invariant carborane-based chalcogenols, containing exopolyhedral B-Se or B-S bonds, as ligands for the formation of photoluminescent copper(I)-based metal-organic chalcogenolate assemblies (MOCHAs). We show that precise tuning of the carborane dipole by changing the carborane isomer from meta- to ortho- allows for control over the MOCHA morphology and regulation of the resulting photophysical properties. Furthermore, microcrystal electron diffraction (MicroED) has been demonstrated as a powerful tool for metal chalcogenide structure elucidation. Through the use of MicroED, one of the isolated materials is determined to consist of zero-dimensional Cu₄(Se-C₂B₁₀H₁₁)₄ clusters with an unprecedented Cu₄Se₄ geometry.

While the study of the tumor microbiome and its effects on cancer biology has expanded considerably over the last few years, most of this research focused on bacteria and viruses, leaving behind the fungal kingdom. Recently, a few studies have demonstrated that specific fungi may promote tumor progression, stressing the importance of comprehensively studying the tumor mycobiome and its effects. To address this, we have characterized the mycobiome in 1,183 human tumors and their adjacent tissues, originating from eight major solid tumor types. Staining and imaging demonstrated the presence of fungi in both cancer and immune cells, with tumor-type specific distribution patterns. Quantitative PCR of the fungal 5.8s rDNA revealed the presence of fungal DNA in all tumor types. To characterize the tumor mycobiome and address potential contamination during tissue handling and processing, we subjected all samples, as well as 295 negative controls of different types, to sequencing of the ITS2 region that is situated between fungal rRNA genes. We found cancer-type specific mycobial signatures with relatively high similarity between tumors and their adjacent tissues. While the fungal mycobiome had a lower species richness as compared to the bacterial microbiome of the same tumors, fungi showed significant co-occurrences with specific bacteria, suggesting the existence of ecological niches within the tumors. We also found significant correlations with clinical parameters such as patient’s age, tumor stage, progression-free survival, overall survival, and response to immune checkpoint blockade therapy. Characterization of the tumor mycobiome may add a biologically relevant, previously overlooked, component to be considered in the study of cancer, including its effects on tumor initiation, progression, diagnosis, and response to therapy. Citation Format: Lian Narunsky Haziza, Gregory D. Sepich-Poore, Ilana Livyatan, Omer Asraf, Cameron Martino, Deborah Nejman, Nancy Gave

Herein, we report the use of sterically invariant carborane-based chalcogenols, containing exopolyhedral B–Se or B–S bonds, as ligands for the formation of photoluminescent copper(I)-based metal–organic chalcogenolate assemblies (MOCHAs). We show that precise tuning of the carborane dipole by changing the carborane isomer from meta to ortho allows for control over the MOCHA morphology and regulation of the resulting photophysical properties. Furthermore, microcrystal electron diffraction (MicroED) has been demonstrated as a powerful tool for metal chalcogenide structure elucidation. Through the use of MicroED, one of the isolated materials is determined to consist of zero-dimensional Cu₄(Se–C₂B₁₀H₁₁)₄ clusters with an unprecedented Cu₄Se₄ geometry.

BackgroundDepression and obesity are highly prevalent, often co-occurring conditions marked by inflammation. Microbiome perturbations are implicated in obesity-inflammation-depression interrelationships, but how the microbiome mechanistically contributes to pathology remains unclear. Metabolomic investigations into microbial neuroactive metabolites may offer mechanistic insights into host-microbe interactions. Using 16S sequencing and untargeted mass spectrometry of saliva, and blood monocyte inflammation regulation assays, we identified key microbes, metabolites and host inflammation in association with depressive symptomatology, obesity, and depressive symptomatology-obesity comorbidity.ResultsGram-negative bacteria with inflammation potential were enriched relative to Gram-positive bacteria in comorbid obesity-depression, supporting the inflammation-oral microbiome link in obesity-depression interrelationships. Oral microbiome was more highly predictive of depressive symptomatology-obesity co-occurrences than of obesity or depressive symptomatology independently, suggesting specific microbial signatures associated with obesity-depression co-occurrences. Mass spectrometry analysis revealed significant changes in levels of signaling molecules of microbiota, microbial or dietary derived signaling peptides and aromatic amino acids among depressive symptomatology, obesity and comorbid obesity-depression. Furthermore, integration of the microbiome and metabolomics data revealed that key oral microbes, many previously shown to have neuroactive potential, co-occurred with potential neuropeptides and biosynthetic precursors of the neurotransmitters dopamine, epinephrine and serotonin.ConclusionsTogether, our findings offer novel insights into oral microbial-brain connection and potential neuroactive metabolites involved.

Background & aimsHyperbaric oxygen therapy (HBOT) is a promising treatment for moderate-to-severe ulcerative colitis. However, our current understanding of the host and microbial response to HBOT remains unclear. This study examined the molecular mechanisms underpinning HBOT using a multi-omic strategy.MethodsPre- and post-intervention mucosal biopsies, tissue, and fecal samples were collected from HBOT phase 2 clinical trials. Biopsies and fecal samples were subjected to shotgun metaproteomics, metabolomics, 16s rRNA sequencing, and metagenomics. Tissue was subjected to bulk RNA sequencing and digital spatial profiling (DSP) for single-cell RNA and protein analysis, and immunohistochemistry was performed. Fecal samples were also used for colonization experiments in IL10-/- germ-free UC mouse models.ResultsProteomics identified negative associations between HBOT response and neutrophil azurophilic granule abundance. DSP identified an HBOT-specific reduction of neutrophil STAT3, which was confirmed by immunohistochemistry. HBOT decreased microbial diversity with a proportional increase in Firmicutes and a secondary bile acid lithocholic acid. A major source of the reduction in diversity was the loss of mucus-adherent taxa, resulting in increased MUC2 levels post-HBOT. Targeted database searching revealed strain-level associations between Akkermansia muciniphila and HBOT response status. Colonization of IL10-/- with stool obtained from HBOT responders resulted in lower colitis activity compared with non-responders, with no differences in STAT3 expression, suggesting complementary but independent host and microbial responses.ConclusionsHBOT reduces host neutrophil STAT3 and azurophilic granule activity in UC patients and changes in microbial composition and metabolism in ways that improve colitis activity. Intestinal microbiota, especially strain level variations in A muciniphila, may contribute to HBOT non-response.

We introduce the operational genomic unit (OGU) method, a metagenome analysis strategy that directly exploits sequence alignment hits to individual reference genomes as the minimum unit for assessing the diversity of microbial communities and their relevance to environmental factors. This approach is independent of taxonomic classification, granting the possibility of maximal resolution of community composition, and organizes features into an accurate hierarchy using a phylogenomic tree. The outputs are suitable for contemporary analytical protocols for community ecology, differential abundance, and supervised learning while supporting phylogenetic methods, such as UniFrac and phylofactorization, that are seldom applied to shotgun metagenomics despite being prevalent in 16S rRNA gene amplicon studies. As demonstrated in two real-world case studies, the OGU method produces biologically meaningful patterns from microbiome data sets. Such patterns further remain detectable at very low metagenomic sequencing depths. Compared with taxonomic unit-based analyses implemented in currently adopted metagenomics tools, and the analysis of 16S rRNA gene amplicon sequence variants, this method shows superiority in informing biologically relevant insights, including stronger correlation with body environment and host sex on the Human Microbiome Project data set and more accurate prediction of human age by the gut microbiomes of Finnish individuals included in the FINRISK 2002 cohort. We provide Woltka, a bioinformatics tool to implement this method, with full integration with the QIIME 2 package and the Qiita web platform, to facilitate adoption of the OGU method in future metagenomics studies. IMPORTANCE Shotgun metagenomics is a powerful, yet computationally challenging, technique compared to 16S rRNA gene amplicon sequencing for decoding the composition and structure of microbial communities. Current analyses of metagenomic data are primarily based on taxonomic classification

Increasing data volumes on high-throughput sequencing instruments such as the NovaSeq 6000 leads to long computational bottlenecks for common metagenomics data preprocessing tasks such as adaptor and primer trimming and host removal. Here, we test whether faster recently developed computational tools (Fastp and Minimap2) can replace widely used choices (Atropos and Bowtie2), obtaining dramatic accelerations with additional sensitivity and minimal loss of specificity for these tasks. Furthermore, the taxonomic tables resulting from downstream processing provide biologically comparable results. However, we demonstrate that for taxonomic assignment, Bowtie2's specificity is still required. We suggest that periodic reevaluation of pipeline components, together with improvements to standardized APIs to chain them together, will greatly enhance the efficiency of common bioinformatics tasks while also facilitating incorporation of further optimized steps running on GPUs, FPGAs, or other architectures. We also note that a detailed exploration of available algorithms and pipeline components is an important step that should be taken before optimization of less efficient algorithms on advanced or nonstandard hardware. IMPORTANCE In shotgun metagenomics studies that seek to relate changes in microbial DNA across samples, processing the data on a computer often takes longer than obtaining the data from the sequencing instrument. Recently developed software packages that perform individual steps in the pipeline of data processing in principle offer speed advantages, but in practice they may contain pitfalls that prevent their use, for example, they may make approximations that introduce unacceptable errors in the data. Here, we show that differences in choices of these components can speed up overall data processing by 5-fold or more on the same hardware while maintaining a high degree of correctness, greatly reducing the time taken to interpret results. This is an important step

This practice report explores a Collaborative Online International Learning (COIL) course focused on awareness and esteem development for women teachers in South Sudan and volunteers associated with a US-based university. Pedagogy of hope was utilized as an educational tool for implementation and evaluation. Assessments of this COIL course focused on data from exit tickets and a final writing assignment. Self-perceptions of the participating teachers were analyzed based on their sense of preparedness, confidence, comfort levels with the class, and any impact the course had on teachers’ sense of teaching as a personal calling. Practitioners and teaching professionals interested in international virtual exchange will find key takeaways related to building partnerships starting with low-stakes initiatives and using COIL to help ignite advances in digital maturity in South Sudan.

Due to the ubiquity of microplastic contamination in coastal waters, there is potential for adverse impacts to organism development. One organism of interest is the daggerblade grass shrimp, Palaemon pugio, an ecologically important species in estuaries along the east coast of North America. We exposed larval grass shrimp to virgin polyethylene microbeads (35 and 58 µm) at a high (0.375 and 1.95 mg/L), medium (0.0375 and 0.195 mg/L), and a low concentration (0.00375 and 0.0195 mg/L), respectively for 23 days to assess mortality, transformation time from larval to juvenile stage, and weight. Average percent mortality was 3.7 to 4.8 times higher in the experimental treatments compared to controls. The greatest proportion of mortality was observed in the first 11 days. Median time for transformation ranged from 20.2 to 20.8 days. Shrimp exposed to the 35 µm beads in the high treatment (20.2 days) transformed significantly faster than the control shrimp (20.8 days). Although development was not delayed and size of the shrimp did not differ, the acute toxicity of microplastics on grass shrimp is a concern due to their role in energy cycling within tidal-creeks. These findings suggest potential population and community level effects following microplastic exposure.

Although it is generally assumed that green household consumer products (HCPs) contain individual compounds that are less toxic and/or more degradable than conventional HCPs, little research on this topic has been conducted. In our assessments, larval grass shrimp (Palaemon pugio) were used in a biodegradation study and juvenile freshwater cladocerans, Daphnia magna, were used in a photodegradation study. In each study, organisms were exposed to nondegraded and degraded treatments consisting of one green HCP and two conventional HCPs in six different categories (laundry detergent, dish detergent, mouthwash, insecticide, dishwasher gel, and all-purpose cleaner). Sensitivity to these products were assessed using 48-h static acute toxicity tests, and the median lethal concentrations (LC50s) then compared using an LC50 ratio test. For grass shrimp, only one green HCP (insecticide) was less toxic than both conventional HCPs. In one category (laundry detergent), the green HCP was the more toxic than either conventional HCP. Following a biodegradation treatment, none of the green product formulations became less toxic, whereas 44.4% of the conventional HCPs demonstrated decreased toxicity. For daphnids, green HCPs in three categories (dish detergent, insecticide, and all-purpose cleaner) were less toxic than both conventional products tested. Following a photodegradation treatment, two green product formulations (dish detergent and dishwasher gel) became less toxic (33.3%), whereas 87.5% of the conventional HCPs demonstrated decreased toxicity. The present study demonstrates that green HCPs are not necessarily less toxic and/or more degradable than their conventional counterparts. These results also suggest that the toxicity and degradability of end-product formulations need to be considered in the overall framework for green product evaluation.

INTRODUCTION: Fear of cancer recurrence (FCR) is a common condition among cancer survivors that can lead to significant levels of distress, anxiety and depression. Online mindfulness programmes may provide the mechanism to support cancer survivors manage FCR and distress, and improve people's well-being over the short, medium and long term. The primary aim of this study is to determine the potential efficacy of MindOnLine, a 9 session mindfulness-based programme for survivors of breast, prostate and colorectal cancer. A formal economic programme will also be conducted. METHODS AND ANALYSIS: A single-blind randomised controlled trial to determine the efficacy and cost-efficacy of a MindOnLine programme for cancer survivors. A total of 400 people living with cancer will be recruited via online advertisements on social media platforms, peak consumer advocacy groups or through outpatient services at healthcare providers across Victoria, Australia. People will be randomly allocated to either the MindOnLine programme (n=200) or waitlist control (n=200). Participant assessments will occur at baseline, at 9 weeks and 9-month follow-up. The primary outcome is change in Fear of Recurrence Index Score total score between baseline and 9 weeks; secondary outcomes are changes in depression and anxiety, quality of life and mindfulness. The economic analysis comprises a cost-consequences analysis where all outcomes will be compared with costs. ETHICS AND DISSEMINATION: Ethics approval was obtained from the Peter MacCallum Cancer Centre (20-53) and Deakin University (2020-284). All participants will be required to provide written informed consent. Findings will be disseminated in peer reviewed journals and among key stakeholder organisations including hospitals, cancer and community organisations and Government. If successful the project will be rolled out nationally with a formal implementation plan. TRIAL REGISTRATION NUMBER: Australian New Zealand Clinical Trials Registry (126200

Rapid and repeated photon cycling has enabled precision metrology and the development of quantum information systems using a variety of atoms and simple molecules. Extending optical cycling to structurally complex molecules would provide new capabilities in these areas, as well as in ultracold chemistry. Increased molecular complexity, however, makes realizing closed optical transitions more difficult. Building on the already established strong optical cycling of diatomic, linear triatomic, and symmetric top molecules, recent theoretical and experimental work has indicated that cycling will be extendable to phenol containing molecules, as well as other asymmetric species. The paradigm for these systems is the use of an optical cycling center bonded to a molecular ligand. Theory has suggested that cycling may be extended to even larger ligands, like naphthalene, pyrene and coronene. Here, we study the optical excitation and vibrational branching of the molecules CaO-2-naphthyl, SrO-2-naphthyl and CaO-1-naphthyl and find only weak decay to excited vibrational states, indicating a promising path to full quantum control and laser cooling of large arene-based molecules.

We introduce the operational genomic unit (OGU) method, a metagenome analysis strategy that directly exploits sequence alignment hits to individual reference genomes as the minimum unit for assessing the diversity of microbial communities and their relevance to environmental factors. This approach is independent of taxonomic classification, granting the possibility of maximal resolution of community composition, and organizes features into an accurate hierarchy using a phylogenomic tree. The outputs are suitable for contemporary analytical protocols for community ecology, differential abundance, and supervised learning while supporting phylogenetic methods, such as UniFrac and phylofactorization, that are seldom applied to shotgun metagenomics despite being prevalent in 16S rRNA gene amplicon studies. As demonstrated in two real-world case studies, the OGU method produces biologically meaningful patterns from microbiome data sets. Such patterns further remain detectable at very low metagenomic sequencing depths. Compared with taxonomic unit-based analyses implemented in currently adopted metagenomics tools, and the analysis of 16S rRNA gene amplicon sequence variants, this method shows superiority in informing biologically relevant insights, including stronger correlation with body environment and host sex on the Human Microbiome Project data set and more accurate prediction of human age by the gut microbiomes of Finnish individuals included in the FINRISK 2002 cohort. We provide Woltka, a bioinformatics tool to implement this method, with full integration with the QIIME 2 package and the Qiita web platform, to facilitate adoption of the OGU method in future metagenomics studies. IMPORTANCE Shotgun metagenomics is a powerful, yet computationally challenging, technique compared to 16S rRNA gene amplicon sequencing for decoding the composition and structure of microbial communities. Current analyses of metagenomic data are primarily based on taxonomic classification

Rapid and repeated photon cycling has enabled precision metrology and the development of quantum information systems using atoms and simple molecules. Extending optical cycling to structurally complex molecules would provide new capabilities in these areas, as well as in ultracold chemistry. Increased molecular complexity, however, makes realizing closed optical transitions more difficult. Building on already established strong optical cycling of diatomic, linear triatomic, and symmetric top molecules, recent work has pointed the way to cycling of larger molecules, including phenoxides. The paradigm for these systems is an optical cycling center bonded to a molecular ligand. Theory has suggested that cycling may be extended to even larger ligands, like naphthalene, pyrene, and coronene. Herein, we study optical excitation and fluorescent vibrational branching of CaO-[Formula: see text], SrO-[Formula: see text], and CaO-[Formula: see text] and find only weak decay to excited vibrational states, indicating a promising path to full quantum control and laser cooling of large arene-based molecules.

BackgroundDepression and obesity are highly prevalent, often co-occurring conditions marked by inflammation. Microbiome perturbations are implicated in obesity-inflammation-depression interrelationships, but how the microbiome mechanistically contributes to pathology remains unclear. Metabolomic investigations into microbial neuroactive metabolites may offer mechanistic insights into host-microbe interactions. Using 16S sequencing and untargeted mass spectrometry of saliva, and blood monocyte inflammation regulation assays, we identified key microbes, metabolites and host inflammation in association with depressive symptomatology, obesity, and depressive symptomatology-obesity comorbidity.ResultsGram-negative bacteria with inflammation potential were enriched relative to Gram-positive bacteria in comorbid obesity-depression, supporting the inflammation-oral microbiome link in obesity-depression interrelationships. Oral microbiome was more highly predictive of depressive symptomatology-obesity co-occurrences than of obesity or depressive symptomatology independently, suggesting specific microbial signatures associated with obesity-depression co-occurrences. Mass spectrometry analysis revealed significant changes in levels of signaling molecules of microbiota, microbial or dietary derived signaling peptides and aromatic amino acids among depressive symptomatology, obesity and comorbid obesity-depression. Furthermore, integration of the microbiome and metabolomics data revealed that key oral microbes, many previously shown to have neuroactive potential, co-occurred with potential neuropeptides and biosynthetic precursors of the neurotransmitters dopamine, epinephrine and serotonin.ConclusionsTogether, our findings offer novel insights into oral microbial-brain connection and potential neuroactive metabolites involved.

While the study of the tumor microbiome and its effects on cancer biology has expanded considerably over the last few years, most of this research focused on bacteria and viruses, leaving behind the fungal kingdom. Recently, a few studies have demonstrated that specific fungi may promote tumor progression, stressing the importance of comprehensively studying the tumor mycobiome and its effects. To address this, we have characterized the mycobiome in 1,183 human tumors and their adjacent tissues, originating from eight major solid tumor types. Staining and imaging demonstrated the presence of fungi in both cancer and immune cells, with tumor-type specific distribution patterns. Quantitative PCR of the fungal 5.8s rDNA revealed the presence of fungal DNA in all tumor types. To characterize the tumor mycobiome and address potential contamination during tissue handling and processing, we subjected all samples, as well as 295 negative controls of different types, to sequencing of the ITS2 region that is situated between fungal rRNA genes. We found cancer-type specific mycobial signatures with relatively high similarity between tumors and their adjacent tissues. While the fungal mycobiome had a lower species richness as compared to the bacterial microbiome of the same tumors, fungi showed significant co-occurrences with specific bacteria, suggesting the existence of ecological niches within the tumors. We also found significant correlations with clinical parameters such as patient’s age, tumor stage, progression-free survival, overall survival, and response to immune checkpoint blockade therapy. Characterization of the tumor mycobiome may add a biologically relevant, previously overlooked, component to be considered in the study of cancer, including its effects on tumor initiation, progression, diagnosis, and response to therapy. Citation Format: Lian Narunsky Haziza, Gregory D. Sepich-Poore, Ilana Livyatan, Omer Asraf, Cameron Martino, Deborah Nejman, Nancy Gave

Background & aimsHyperbaric oxygen therapy (HBOT) is a promising treatment for moderate-to-severe ulcerative colitis. However, our current understanding of the host and microbial response to HBOT remains unclear. This study examined the molecular mechanisms underpinning HBOT using a multi-omic strategy.MethodsPre- and post-intervention mucosal biopsies, tissue, and fecal samples were collected from HBOT phase 2 clinical trials. Biopsies and fecal samples were subjected to shotgun metaproteomics, metabolomics, 16s rRNA sequencing, and metagenomics. Tissue was subjected to bulk RNA sequencing and digital spatial profiling (DSP) for single-cell RNA and protein analysis, and immunohistochemistry was performed. Fecal samples were also used for colonization experiments in IL10-/- germ-free UC mouse models.ResultsProteomics identified negative associations between HBOT response and neutrophil azurophilic granule abundance. DSP identified an HBOT-specific reduction of neutrophil STAT3, which was confirmed by immunohistochemistry. HBOT decreased microbial diversity with a proportional increase in Firmicutes and a secondary bile acid lithocholic acid. A major source of the reduction in diversity was the loss of mucus-adherent taxa, resulting in increased MUC2 levels post-HBOT. Targeted database searching revealed strain-level associations between Akkermansia muciniphila and HBOT response status. Colonization of IL10-/- with stool obtained from HBOT responders resulted in lower colitis activity compared with non-responders, with no differences in STAT3 expression, suggesting complementary but independent host and microbial responses.ConclusionsHBOT reduces host neutrophil STAT3 and azurophilic granule activity in UC patients and changes in microbial composition and metabolism in ways that improve colitis activity. Intestinal microbiota, especially strain level variations in A muciniphila, may contribute to HBOT non-response.

Cancer-microbe associations have been explored for centuries, but cancer-associated fungi have rarely been examined. Here, we comprehensively characterize the cancer mycobiome within 17,401 patient tissue, blood, and plasma samples across 35 cancer types in four independent cohorts. We report fungal DNA and cells at low abundances across many major human cancers, with differences in community compositions that differ among cancer types, even when accounting for technical background. Fungal histological staining of tissue microarrays supported intratumoral presence and frequent spatial association with cancer cells and macrophages. Comparing intratumoral fungal communities with matched bacteriomes and immunomes revealed co-occurring bi-domain ecologies, often with permissive, rather than competitive, microenvironments and distinct immune responses. Clinically focused assessments suggested prognostic and diagnostic capacities of the tissue and plasma mycobiomes, even in stage I cancers, and synergistic predictive performance with bacteriomes.

Increasing data volumes on high-throughput sequencing instruments such as the NovaSeq 6000 leads to long computational bottlenecks for common metagenomics data preprocessing tasks such as adaptor and primer trimming and host removal. Here, we test whether faster recently developed computational tools (Fastp and Minimap2) can replace widely used choices (Atropos and Bowtie2), obtaining dramatic accelerations with additional sensitivity and minimal loss of specificity for these tasks. Furthermore, the taxonomic tables resulting from downstream processing provide biologically comparable results. However, we demonstrate that for taxonomic assignment, Bowtie2's specificity is still required. We suggest that periodic reevaluation of pipeline components, together with improvements to standardized APIs to chain them together, will greatly enhance the efficiency of common bioinformatics tasks while also facilitating incorporation of further optimized steps running on GPUs, FPGAs, or other architectures. We also note that a detailed exploration of available algorithms and pipeline components is an important step that should be taken before optimization of less efficient algorithms on advanced or nonstandard hardware. IMPORTANCE In shotgun metagenomics studies that seek to relate changes in microbial DNA across samples, processing the data on a computer often takes longer than obtaining the data from the sequencing instrument. Recently developed software packages that perform individual steps in the pipeline of data processing in principle offer speed advantages, but in practice they may contain pitfalls that prevent their use, for example, they may make approximations that introduce unacceptable errors in the data. Here, we show that differences in choices of these components can speed up overall data processing by 5-fold or more on the same hardware while maintaining a high degree of correctness, greatly reducing the time taken to interpret results. This is an important step

Despite advances in sequencing, lack of standardization makes comparisons across studies challenging and hampers insights into the structure and function of microbial communities across multiple habitats on a planetary scale. Here we present a multi-omics analysis of a diverse set of 880 microbial community samples collected for the Earth Microbiome Project. We include amplicon (16S, 18S, ITS) and shotgun metagenomic sequence data, and untargeted metabolomics data (liquid chromatography-tandem mass spectrometry and gas chromatography mass spectrometry). We used standardized protocols and analytical methods to characterize microbial communities, focusing on relationships and co-occurrences of microbially related metabolites and microbial taxa across environments, thus allowing us to explore diversity at extraordinary scale. In addition to a reference database for metagenomic and metabolomic data, we provide a framework for incorporating additional studies, enabling the expansion of existing knowledge in the form of an evolving community resource. We demonstrate the utility of this database by testing the hypothesis that every microbe and metabolite is everywhere but the environment selects. Our results show that metabolite diversity exhibits turnover and nestedness related to both microbial communities and the environment, whereas the relative abundances of microbially related metabolites vary and co-occur with specific microbial consortia in a habitat-specific manner. We additionally show the power of certain chemistry, in particular terpenoids, in distinguishing Earth's environments (for example, terrestrial plant surfaces and soils, freshwater and marine animal stool), as well as that of certain microbes including Conexibacter woesei (terrestrial soils), Haloquadratum walsbyi (marine deposits) and Pantoea dispersa (terrestrial plant detritus). This Resource provides insight into the taxa and metabolites within microbial communities from diverse habitats across Ear

There is growing evidence that the microbiome is involved in development and treatment of many human diseases, including prostate cancer. There are several potential pathways for microbiome-based mechanisms for the development of prostate cancer: direct impacts of microbes or microbial products in the prostate or the urine, and indirect impacts from microbes or microbial products in the gastrointestinal tract. Unique microbial signatures have been identified within the stool, oral cavity, tissue, urine, and blood of prostate cancer patients, but studies vary in their findings. Recent studies describe potential diagnostic and therapeutic applications of the microbiome, but further clinical investigation is needed. In this review, we explore the existing literature on the discovery of the human microbiome and its relationship to prostate cancer.

Microbial communities contain a broad phylogenetic diversity of organisms; however, the majority of methods center on describing bacteria and archaea. Fungi are important symbionts in many ecosystems and are potentially important members of the human microbiome, beyond those that can cause disease. To expand our analysis of microbial communities to include data from the fungal internal transcribed spacer (ITS) region, five candidate DNA extraction kits were compared against our standardized protocol for describing bacteria and archaea using 16S rRNA gene amplicon- and shotgun metagenomics sequencing. The results are presented considering a diverse panel of host-associated and environmental sample types and comparing the cost, processing time, well-to-well contamination, DNA yield, limit of detection and microbial community composition among protocols. Across all criteria, the MagMAX Microbiome kit was found to perform best. The PowerSoil Pro kit performed comparably but with increased cost per sample and overall processing time. The Zymo MagBead, NucleoMag Food and Norgen Stool kits were included.

Human untargeted metabolomics studies annotate only ~10% of molecular features. We introduce reference-data-driven analysis to match metabolomics tandem mass spectrometry (MS/MS) data against metadata-annotated source data as a pseudo-MS/MS reference library. Applying this approach to food source data, we show that it increases MS/MS spectral usage 5.1-fold over conventional structural MS/MS library matches and allows empirical assessment of dietary patterns from untargeted data.

Feature selection is indispensable in microbiome data analysis, but it can be particularly challenging as microbiome data sets are high dimensional, underdetermined, sparse and compositional. Great efforts have recently been made on developing new methods for feature selection that handle the above data characteristics, but almost all methods were evaluated based on performance of model predictions. However, little attention has been paid to address a fundamental question: how appropriate are those evaluation criteria? Most feature selection methods often control the model fit, but the ability to identify meaningful subsets of features cannot be evaluated simply based on the prediction accuracy. If tiny changes to the data would lead to large changes in the chosen feature subset, then many selected features are likely to be a data artifact rather than real biological signal. This crucial need of identifying relevant and reproducible features motivated the reproducibility evaluation criterion such as Stability, which quantifies how robust a method is to perturbations in the data. In our paper, we compare the performance of popular model prediction metrics (MSE or AUC) with proposed reproducibility criterion Stability in evaluating four widely used feature selection methods in both simulations and experimental microbiome applications with continuous or binary outcomes. We conclude that Stability is a preferred feature selection criterion over model prediction metrics because it better quantifies the reproducibility of the feature selection method.

Along the South Carolina coast (U.S.) where the ecologically and economically important eastern oyster (Crassostrea virginica) forms extensive intertidal reefs, recent surface water surveys found that fibers, fragments, and microscopic tire particles represented 43.6%, 30.9%, and 17.7% of the total microplastics, respectively. The aim of this study was to characterize accumulation and depuration of these particles in eastern oysters. Oysters were exposed to purple polyethylene fibers, green nylon fragments, or micronized crumb rubber at a concentration of 5000 microplastics/L, and sacrificed after 0, 24, 48, and 96 h to characterize uptake. Following 96 h, remaining oysters were transferred to microplastic-free brackish water and sacrificed at 24, 48, and 96 h to characterize depuration. For fibers and fragments, levels increased in a nonlinear fashion reaching 1.61 ± 0.6 particles/g w. w. (mean ± SE) and 0.46 ± 0.1 particles/g w. w. after 96 h, respectively. Conditional uptake clearance rate constants (ku) were estimated to be 0.0084 and 0.0025 mL/g*h for fibers and fragments, respectively. For crumb rubber, levels increased in a linear fashion reaching 3.62 ± 0.8 particles/g w. w. after 96 h, and the ku value was estimated to be 0.0077 mL/g*h. Depuration was best described using a two-compartment (double exponential) model suggesting the presence of fast and slow compartments. Conditional depuration rate constants (kd) for the slow compartments were 0.0084, 0.0205, and 0.0048/h for fibers, fragments, and crumb rubber, respectively. These results demonstrate accumulation and depuration of microplastics in eastern oysters is size-and shape-dependent. Depuration, which is a common practice for shellfish safety, is an effective way to reduce microplastic loads in eastern oysters, but the minimum recommended time of 44 h would only reduce loads of these particles by 55.5–67.6%.

Due to the ubiquity of microplastic contamination in coastal waters, there is potential for adverse impacts to organism development. One organism of interest is the daggerblade grass shrimp, Palaemon pugio, an ecologically important species in estuaries along the east coast of North America. We exposed larval grass shrimp to virgin polyethylene microbeads (35 and 58 µm) at a high (0.375 and 1.95 mg/L), medium (0.0375 and 0.195 mg/L), and a low concentration (0.00375 and 0.0195 mg/L), respectively for 23 days to assess mortality, transformation time from larval to juvenile stage, and weight. Average percent mortality was 3.7 to 4.8 times higher in the experimental treatments compared to controls. The greatest proportion of mortality was observed in the first 11 days. Median time for transformation ranged from 20.2 to 20.8 days. Shrimp exposed to the 35 µm beads in the high treatment (20.2 days) transformed significantly faster than the control shrimp (20.8 days). Although development was not delayed and size of the shrimp did not differ, the acute toxicity of microplastics on grass shrimp is a concern due to their role in energy cycling within tidal-creeks. These findings suggest potential population and community level effects following microplastic exposure.

Although it is generally assumed that green household consumer products (HCPs) contain individual compounds that are less toxic and/or more degradable than conventional HCPs, little research on this topic has been conducted. In our assessments, larval grass shrimp (Palaemon pugio) were used in a biodegradation study and juvenile freshwater cladocerans, Daphnia magna, were used in a photodegradation study. In each study, organisms were exposed to nondegraded and degraded treatments consisting of one green HCP and two conventional HCPs in six different categories (laundry detergent, dish detergent, mouthwash, insecticide, dishwasher gel, and all-purpose cleaner). Sensitivity to these products were assessed using 48-h static acute toxicity tests, and the median lethal concentrations (LC50s) then compared using an LC50 ratio test. For grass shrimp, only one green HCP (insecticide) was less toxic than both conventional HCPs. In one category (laundry detergent), the green HCP was the more toxic than either conventional HCP. Following a biodegradation treatment, none of the green product formulations became less toxic, whereas 44.4% of the conventional HCPs demonstrated decreased toxicity. For daphnids, green HCPs in three categories (dish detergent, insecticide, and all-purpose cleaner) were less toxic than both conventional products tested. Following a photodegradation treatment, two green product formulations (dish detergent and dishwasher gel) became less toxic (33.3%), whereas 87.5% of the conventional HCPs demonstrated decreased toxicity. The present study demonstrates that green HCPs are not necessarily less toxic and/or more degradable than their conventional counterparts. These results also suggest that the toxicity and degradability of end-product formulations need to be considered in the overall framework for green product evaluation.

Despite advances in sequencing, lack of standardization makes comparisons across studies challenging and hampers insights into the structure and function of microbial communities across multiple habitats on a planetary scale. Here we present a multi-omics analysis of a diverse set of 880 microbial community samples collected for the Earth Microbiome Project. We include amplicon (16S, 18S, ITS) and shotgun metagenomic sequence data, and untargeted metabolomics data (liquid chromatography-tandem mass spectrometry and gas chromatography mass spectrometry). We used standardized protocols and analytical methods to characterize microbial communities, focusing on relationships and co-occurrences of microbially related metabolites and microbial taxa across environments, thus allowing us to explore diversity at extraordinary scale. In addition to a reference database for metagenomic and metabolomic data, we provide a framework for incorporating additional studies, enabling the expansion of existing knowledge in the form of an evolving community resource. We demonstrate the utility of this database by testing the hypothesis that every microbe and metabolite is everywhere but the environment selects. Our results show that metabolite diversity exhibits turnover and nestedness related to both microbial communities and the environment, whereas the relative abundances of microbially related metabolites vary and co-occur with specific microbial consortia in a habitat-specific manner. We additionally show the power of certain chemistry, in particular terpenoids, in distinguishing Earth's environments (for example, terrestrial plant surfaces and soils, freshwater and marine animal stool), as well as that of certain microbes including Conexibacter woesei (terrestrial soils), Haloquadratum walsbyi (marine deposits) and Pantoea dispersa (terrestrial plant detritus). This Resource provides insight into the taxa and metabolites within microbial communities from diverse habitats across Ear

According to the Pipeline and Hazardous Material Safety Administration (PHMSA), thirdparty damage is a leading cause of natural gas pipeline accidents. Although the risk of third-party damage has been widely studied in the literature, current models do not capture a sufficiently comprehensive set of up-to-date root cause factors and their dependencies. This limits their ability to achieve an accurate risk assessment that can be traced to meaningful elements of an excavation. This paper presents the construction, verification, and validation of a probabilistic Bayesian network model for third-party excavation risk assessment, BaNTERA. The model was constructed and its performance verified using the best available industry data and previous models from multiple sources. Historical industry data and nationwide statistics were compared with BaNTERA’s damage rate predictions to validate the model. The result of this work is a comprehensive risk model for the third-party damage problem in natural gas pipelines.

This practice report explores a Collaborative Online International Learning (COIL) course focused on awareness and esteem development for women teachers in South Sudan and volunteers associated with a US-based university. Pedagogy of hope was utilized as an educational tool for implementation and evaluation. Assessments of this COIL course focused on data from exit tickets and a final writing assignment. Self-perceptions of the participating teachers were analyzed based on their sense of preparedness, confidence, comfort levels with the class, and any impact the course had on teachers’ sense of teaching as a personal calling. Practitioners and teaching professionals interested in international virtual exchange will find key takeaways related to building partnerships starting with low-stakes initiatives and using COIL to help ignite advances in digital maturity in South Sudan.

We present a reduction and analysis of the \textit{James Webb Space Telescope} (JWST) SMACS~0723 field using new post-launch calibrations to conduct a search for ultra-high-redshift galaxies ($z > 9$) present within the Epoch of Reionisation. We conduct this search by modelling photometric redshifts in several ways for all sources and by applying conservative magnitude cuts ($m_{\rm F200W} < 28$) to identify strong Lyman breaks greater than 1 magnitude. We find four $z > 9$ candidate galaxies which have not previously been identified, with one object at $z = 11.5$, and another which is possibly a close pair of galaxies. We measure redshifts for candidate galaxies from other studies and find the recovery rate to be only 23 per cent, with many being assigned lower redshift, dusty solutions in our work. Most of our $z > 9$ sample show evidence for Balmer-breaks, or extreme emission lines from H$\beta$ and [OIII], demonstrating that the stellar populations could be advanced in age or very young depending on the cause of the F444W excess. We discuss the resolved structures of these early galaxies and find that the S\'{e}rsic indices reveal a mixture of light concentration levels, but that the sizes of all our systems are exceptionally small ($< 0.5$~kpc). These systems have stellar masses M$_{*} \sim 10^{9.0}$ M$_{\odot}$, with our $z \sim 11.5$ candidate a dwarf galaxy with a stellar mass M$_{*} \sim 10^{7.8}$ -- $10^{8.2}$ M$_{\odot}$. These candidate ultra high-redshift galaxies are excellent targets for future NIRSpec observations aimed to better understand their physical nature., Comment: Updated to accepted mnras manuscript, 12 pages, 8 figures, 6 tables, added section 3.3 and Table 5

Grayson County, Virginia is home to some of the largest Christmas tree productions in the United States. With this production comes the use of a multitude of pesticides, including the insecticide Sniper, Dimethoate, and Safari; the miticide Endivor and the herbicide Roundup. These pesticides have a varying effect on aquatic life, especially on benthic macroinvertebrates. This project focused on collecting benthic macroinvertebrate samples scattered throughout Grayson County and then analyzing the samples to determine what the stream health is at the current time of year. Overall, the stream health is good and has a lot of macroinvertebrates that are sensitive to pollution present. Future research on this project should include testing throughout different times of year (spring and summer) as well as testing upstream and downstream of Christmas tree farms, the following experiment was conducted upstream of Christmas tree farms.

There is a growing body of literature in the field of environmental education that draws from the phenomenological tradition in theorizing about human-animal interactions. I am inspired by the eco-phenomenology of Phillip G. Payne and aim here to further an educational pedagogy of intercorporeal relations and to conceptualize M:W as “an active experiential and existential site of and for inquiry in and with various natures and environments.” From the animal welfarist perspective, some work has also been done about how these interactions occur in the contexts of zoos and wildlife sanctuaries, and how they can be mutually enriching for non/humans; Lindsey Mehrkam, Nicolle Verdi, and Clive Wynne have specifically studied captive wolves and wolf-dogs in this regard. Holding all these schools of thought in mind, this essay lies at the four-way intersection of human-animal studies (HAS), anthropological methodology, environmental education, and phenomenology. More specifically, I endeavor to bring the anthropological framework of dynamic embodiment—which draws heavily from phenomenology but has been largely humancentric—firmly into conversation with these other intellectual genealogies.