Phables: from fragmented assemblies to high-quality bacteriophage genomes.

MOTIVATION: Microbial communities have a profound impact on both human health and various environments. Viruses infecting bacteria, known as bacteriophages or phages, play a key role in modulating bacterial communities within environments. High-quality phage genome sequences are essential for advancing our understanding of phage biology, enabling comparative genomics studies and developing phage-based diagnostic tools. Most available viral identification tools consider individual sequences to determine whether they are of viral origin. As a result of challenges in viral assembly, fragmentation of genomes can occur, and existing tools may recover incomplete genome fragments. Therefore, the identification and characterization of novel phage genomes remain a challenge, leading to the need of improved approaches for phage genome recovery. RESULTS: We introduce Phables, a new computational method to resolve phage genomes from fragmented viral metagenome assemblies. Phables identifies phage-like components in the assembly graph, models each component as a flow network, and uses graph algorithms and flow decomposition techniques to identify genomic paths. Experimental results of viral metagenomic samples obtained from different environments show that Phables recovers on average over 49% more high-quality phage genomes compared to existing viral identification tools. Furthermore, Phables can resolve variant phage genomes with over 99% average nucleotide identity, a distinction that existing tools are unable to make. AVAILABILITY AND IMPLEMENTATION: Phables is available on GitHub at https://github.com/Vini2/phables.

Lateral Pelvic Nodal Management and Patterns of Failure in Patients Receiving Short-Course Radiation for Locally Advanced Rectal Cancer.

BACKGROUND: Management of lateral pelvic lymph nodes in locally advanced rectal cancer is controversial, with limited data indicating the optimal approach. In addition, no data exist regarding the treatment of lateral nodes in the setting of short-course radiation and nonoperative intent. OBJECTIVE: To evaluate a novel approach incorporating simultaneous integrated boost to suspicious lateral nodes. DESIGN: A retrospective study. SETTING: This study was conducted at a large tertiary referral center. PATIENTS: Patients treated with radiation therapy and consolidation chemotherapy were included. All primary tumors underwent biopsy confirmation and disease staging with pelvic MRI. INTERVENTIONS: Primary tumors were biopsy proven and staged with pelvic MRI. A subset of lateral pelvic lymph node patients received a simultaneous integrated boost of 35 Gy in 5 fractions. Then, chemotherapy was administered, with the majority receiving modified folinic acid, fluorouracil, and oxaliplatin. Clinical partial response required total mesorectal excision. MAIN OUTCOME MEASURES: Patterns of failure and survival analyses by subgroup were assessed. Outcomes based on receipt of radiation were compared across node status. RESULTS: Between January 2017 and January 2022, 155 patients were treated with short-course chemotherapy, with 121 included in the final analysis. Forty-nine percent of patients underwent nonoperative management. The median follow-up was 36 months and the median age was 58 years. Thirty-eight patients (26%) had positive lateral pelvic lymph nodes. Comparing lateral node status, progression-free survival was significantly worse for patients with positive disease ( p < 0.001), with a trend for worse overall survival. Receipt of nodal boost in patients with lateral nodes resulted in meaningful locoregional control. Nodal boost did not contribute to additional acute or late GI toxicity. LIMITATIONS: Limitations include retrospective nature and lack of lateral node pathology; however, a thorough radiographic review was performed. CONCLUSIONS: Lateral node-positive rectal cancer is correlated with worse oncologic outcomes and higher locoregional failure. Boost to clinically positive lateral nodes is a safe approach in the setting of short course radiation and in those receiving nonoperative intent. See Video Abstract. MANEJO DE LOS GANGLIOS PLVICOS LATERALES Y PATRONES DE FALLA EN PACIENTES QUE RECIBEN RADIACIN DE CICLO CORTO PARA EL CNCER DE RECTO LOCALMENTE AVANZADO: ANTECEDENTES:El manejo de los ganglios linfáticos pélvicos laterales en el cáncer de recto localmente avanzado es controvertido, con datos limitados que indiquen el abordaje óptimo. Además, no existen datos sobre el tratamiento de los ganglios linfáticos laterales en el contexto de la radiación de curso corto y la intención no operatoria.OBJETIVO:Evaluamos un enfoque novedoso que incorpora sobreimpresión integrada simultánea (SIB) a los linfonodos laterales sospechosos.DISEÑO:Este fue un estudio retrospectivo.ESCENARIO:Este estudio se realizó en un gran centro de referencia terciario.PACIENTES:Se incluyeron pacientes tratados con radiación y quimioterapia de consolidación. Todos los tumores primarios se confirmaron mediante biopsia y la enfermedad se estadificó con resonancia magnética pélvica.INTERVENCIONES:Los tumores primarios se confirmaron mediante biopsia y se estadificaron con RM pélvica. Un subconjunto de pacientes con linfonodos pélvicos laterales (LPLN) recibió SIB a 35 Gy en 5 fracciones. Luego, se administró quimioterapia y la mayoría recibió mFOLFOX. La respuesta clínica parcial requirió la escisión total del mesorrecto.PRINCIPALES MEDIDAS DE RESULTADO:Se evaluaron los patrones de fracaso y los análisis de supervivencia por subgrupo. Los resultados basados en el esquema de radiación se compararon según el estado de los ganglios.RESULTADOS:Entre enero de 2017 y enero de 2022, 155 pacientes fueron tratados con ciclo corto y quimioterapia con 121 incluidos en el análisis final. El 49% se sometió a manejo no operatorio. La mediana de seguimiento fue de 36 meses y la mediana de edad fue de 58 años. 38 pacientes (26%) tuvieron LPLN positivos. Comparando el estado de los ganglios laterales, la supervivencia libre de progresión fue significativamente peor para los pacientes con LPLN positiva ( p < 0,001) con una tendencia a una peor supervivencia global. La recepción de refuerzo nodal en pacientes con nodos laterales dio como resultado un control locorregional significativo. La sobreimpresión ganglionar no contribuyó a la toxicidad GI aguda o tardía adicional.LIMITACIONES:Las limitaciones incluyeron la naturaleza retrospectiva y la falta de patología de los ganglios linfáticos laterales; sin embargo, se realizó una revisión radiográfica exhaustiva.CONCLUSIONES:El cáncer de recto con ganglio lateral positivo se correlaciona con peores resultados oncológicos y mayor fracaso locorregional. La sobreimpresión a los ganglios laterales clínicamente positivos es un enfoque seguro en el contexto de un curso corto y en aquellos que siguen un manejo no operatorio. (Traducción-Dr. Felipe Bellolio ).

Why foreign STEM PhDs are unlikely to work for US technology startups.

Visa policies to retain United States-trained STEM PhDs are of central importance to national innovation and economic competitiveness. There is also growing interest in "startup" visas that stimulate entrepreneurial activity and job creation, particularly in technology sectors. However, there is little understanding of how visa policies might influence foreign PhDs' employment in technology startups. This study investigates differences between 2,324 foreign and US PhDs from US research universities using a longitudinal survey of individuals' preferences and characteristics during graduate school and their subsequent employment in a startup or established firm. Among PhDs whose first job is industrial research & development, 15.8% of US PhDs work in a startup compared with 6.8% of foreign PhDs. Foreign PhDs are as likely as US PhDs to apply to and receive offers for startup jobs, but conditional on receiving an offer, they are 56% less likely to work in a startup. This disparity is partially explained by differences in visa sponsorship between startups and established firms and not by foreign PhDs' preferences for established firm jobs, risk tolerance, or preference for higher pay. Foreign PhDs who first work in an established firm and subsequently receive a green card are more likely to move to a startup than another established firm, suggesting that permanent residency facilitates startup employment. These findings suggest that US visa policies may deter foreign PhDs from working in startups, thereby restricting startups' access to a large segment of the STEM PhD workforce and impairing startups' ability to contribute to innovation and economic growth.

Adaptive evolution of sulfite tolerance in Brettanomyces bruxellensis.

Brettanomyces bruxellensis is considered one of the most problematic microbes associated with wine production. Sulfur dioxide is commonly used to inhibit the growth of B. bruxellensis and limit the potential wine spoilage. Brettanomyces bruxellensis wine isolates can grow at higher concentrations of this preservative than isolates from other sources. Thus, it has been suggested that the use of sulfite may have selected for B. bruxellensis strains better adapted to survive in the winemaking environment. We utilized laboratory adaptive evolution to determine the potential for this to occur. Three B. bruxellensis strains, representative of known genetic variation within the species, were subjected to increasing sublethal sulfur dioxide concentrations. Individual clones isolated from evolved populations displayed enhanced sulfite tolerance, ranging from 1.6 to 2.5 times higher than the corresponding parental strains. Whole-genome sequencing of sulfite-tolerant clones derived from two of the parental strains revealed structural variations affecting 270 genes. The region containing the sulfite efflux pump encoding gene, SSU1, showed clear copy number variants in all sequenced clones. Regardless of parental strain genetic background, SSU1 copy number changes were reproducibly associated with one SSU1 haplotype. This work clearly demonstrates adaptive evolution of B. bruxellensis when exposed to sublethal sulfites and suggests that, similar to Saccharomyces cerevisiae wine yeast, the mechanism responsible involves the gene SSU1.

Population sequencing reveals clonal diversity and ancestral inbreeding in the grapevine cultivar Chardonnay.

Chardonnay is the basis of some of the world's most iconic wines and its success is underpinned by a historic program of clonal selection. There are numerous clones of Chardonnay available that exhibit differences in key viticultural and oenological traits that have arisen from the accumulation of somatic mutations during centuries of asexual propagation. However, the genetic variation that underlies these differences remains largely unknown. To address this knowledge gap, a high-quality, diploid-phased Chardonnay genome assembly was produced from single-molecule real time sequencing, and combined with re-sequencing data from 15 different Chardonnay clones. There were 1620 markers identified that distinguish the 15 clones. These markers were reliably used for clonal identification of independently sourced genomic material, as well as in identifying a potential genetic basis for some clonal phenotypic differences. The predicted parentage of the Chardonnay haplomes was elucidated by mapping sequence data from the predicted parents of Chardonnay (Gouais blanc and Pinot noir) against the Chardonnay reference genome. This enabled the detection of instances of heterosis, with differentially-expanded gene families being inherited from the parents of Chardonnay. Most surprisingly however, the patterns of nucleotide variation present in the Chardonnay genome indicate that Pinot noir and Gouais blanc share an extremely high degree of kinship that has resulted in the Chardonnay genome displaying characteristics that are indicative of inbreeding.

New genome assemblies reveal patterns of domestication and adaptation across Brettanomyces (Dekkera) species.

BACKGROUND: Yeasts of the genus Brettanomyces are of significant interest, both for their capacity to spoil, as well as their potential to positively contribute to different industrial fermentations. However, considerable variance exists in the depth of research and knowledgebase of the five currently known species of Brettanomyces. For instance, Brettanomyces bruxellensis has been heavily studied and many resources are available for this species, whereas Brettanomyces nanus is rarely studied and lacks a publicly available genome assembly altogether. The purpose of this study is to fill this knowledge gap and explore the genomic adaptations that have shaped the evolution of this genus. RESULTS: Strains for each of the five widely accepted species of Brettanomyces (Brettanomyces anomalus, B. bruxellensis, Brettanomyces custersianus, Brettanomyces naardenensis, and B. nanus) were sequenced using a combination of long- and short-read sequencing technologies. Highly contiguous assemblies were produced for each species. Structural differences between the species' genomes were observed with gene expansions in fermentation-relevant genes (particularly in B. bruxellensis and B. nanus) identified. Numerous horizontal gene transfer (HGT) events in all Brettanomyces species', including an HGT event that is probably responsible for allowing B. bruxellensis and B. anomalus to utilize sucrose were also observed. CONCLUSIONS: Genomic adaptations and some evidence of domestication that have taken place in Brettanomyces are outlined. These new genome assemblies form a valuable resource for future research in Brettanomyces.

Comparative genome analysis proposes three new Aureobasidium species isolated from grape juice.

Aureobasidium pullulans is the most abundant and ubiquitous species within the genus and is also considered a core component of the grape juice microflora. So far, a small number of other Aureobasidium species have been reported, that in contrast to A. pullulans, appear far more constrained to specific habitats. It is unknown whether grape juice is a reservoir of novel Aureobasidium species, overlooked in the course of conventional morphological and meta-barcoding analyses. In this study, eight isolates from grape juice taxonomically classified as Aureobasidium through ITS sequencing were subjected to whole-genome phylogenetic, synteny and nucleotide identity analyses, which revealed three isolates to likely represent newly discovered Aureobasidium species. Analyses of ITS and metagenomic sequencing datasets show that these species can be present in grape juice samples from different locations and vintages. Functional annotation revealed the Aureobasidium isolates possess the genetic potential to support growth on the surface of plants and grapes. However, the loss of several genes associated with tolerance to diverse environmental stresses suggest a more constrained ecological range than A. pullulans.

Inactivating Mutations in Irc7p Are Common in Wine Yeasts, Attenuating Carbon-Sulfur ß-Lyase Activity and Volatile Sulfur Compound Production.

During alcoholic fermentation of grape sugars, wine yeasts produce a range of secondary metabolites that play an important role in the aroma profile of wines. In this study, we have explored the ability of a large number of wine yeast strains to modulate wine aroma composition, focusing on the release of the "fruity" thiols 3-mercaptohexan-1-ol (3-MH) and 4-mercapto-4-methylpentan-2-one (4-MMP) from their respective cysteinylated nonvolatile precursors. The role of the yeast gene IRC7 in thiol release has been well established, and it has been shown that a 38-bp deletion found in many wine strains cause them to express a truncated version of Irc7p that does not possess cysteine-S-conjugate ß-lyase activity. In our data, we find that IRC7 allele length alone does not fully explain the capacity of a strain to release thiols. Screening of a large number of strains coupled with analysis of genomic sequence data allowed us to identify several previously undescribed single-nucleotide polymorphisms (SNPs) in IRC7 that, when coupled with allele length, more robustly explain the ability of a particular yeast strain to release thiols from their cysteinylated precursors. We also demonstrate that allelic variation of IRC7 not only affects the release of thiols but modulates the formation of negative volatile sulfur compounds from the amino acid cysteine. The results of this study provide winemakers with an improved understanding of the genetic determinants that affect wine aroma and flavor, which can be used to guide the choice of yeast strains that are fit for purpose.IMPORTANCE Volatile sulfur compounds contribute to wine aromas that may be considered pleasant, such as "tropical," "passionfruit," and "guava," as well as aromas that are considered undesirable, such as "rotten eggs," "onions," and "sewer." During fermentation, wine yeasts release some of these compounds from odorless precursor molecules, a process that is most efficient when performed by yeasts that express active forms of the protein Irc7p. We show that most wine yeasts carry mutations that reduce activity of this protein, affecting the formation of volatile sulfur compounds that impart both pleasant and unpleasant aromas. The results provide winemakers with guidance on the choice of yeasts that can emphasize or deemphasize this particular contribution to wine quality.

Treatment response as predictor for brain metastasis in triple negative breast cancer: A score-based model.

BACKGROUND: Triple negative breast cancer (TNBC) has worse prognosis than other subtypes of breast cancer, and many patients develop brain metastasis (BM). We developed a simple predictive model to stratify the risk of BM in TNBC patients receiving neo-adjuvant chemotherapy (NAC), surgery, and radiation therapy (RT). METHODS: Patients with TNBC who received NAC, surgery, and RT were included. Cox proportional hazards method was used to evaluate factors associated with BM. Significant factors predictive for BM on multivariate analysis (MVA) were used to develop a risk score. Patients were divided into three risk groups: low, intermediate, and high. A receiver operating characteristic (ROC) curve was drawn to evaluate the value of the risk group in predicting BM. This predictive model was externally validated. RESULTS: A total of 160 patients were included. The median follow-up was 47.4 months. The median age at diagnosis was 49.9 years. The 2-year freedom from BM was 90.5%. Persistent lymph node positivity, HR 8.75 (1.76-43.52, P = 0.01), and lack of downstaging, HR 3.46 (1.03-11.62, P = 0.04), were significant predictors for BM. The 2-year rate of BM was 0%, 10.7%, and 30.3% (P < 0.001) in patients belonging to low-, intermediate-, and high-risk groups, respectively. Area under the ROC curve was 0.81 (P < 0.001). This model was externally validated (C-index = 0.79). CONCLUSIONS: Lack of downstaging and persistent lymph node positivity after NAC are associated with development of BM in TNBC. This model can be used by the clinicians to stratify patients into the three risk groups to identify those at increased risk of developing BM and potentially impact surveillance strategies.

Purge Haplotigs: allelic contig reassignment for third-gen diploid genome assemblies.

BACKGROUND: Recent developments in third-gen long read sequencing and diploid-aware assemblers have resulted in the rapid release of numerous reference-quality assemblies for diploid genomes. However, assembly of highly heterozygous genomes is still problematic when regional heterogeneity is so high that haplotype homology is not recognised during assembly. This results in regional duplication rather than consolidation into allelic variants and can cause issues with downstream analysis, for example variant discovery, or haplotype reconstruction using the diploid assembly with unpaired allelic contigs. RESULTS: A new pipeline-Purge Haplotigs-was developed specifically for third-gen sequencing-based assemblies to automate the reassignment of allelic contigs, and to assist in the manual curation of genome assemblies. The pipeline uses a draft haplotype-fused assembly or a diploid assembly, read alignments, and repeat annotations to identify allelic variants in the primary assembly. The pipeline was tested on a simulated dataset and on four recent diploid (phased) de novo assemblies from third-generation long-read sequencing, and compared with a similar tool. After processing with Purge Haplotigs, haploid assemblies were less duplicated with minimal impact on genome completeness, and diploid assemblies had more pairings of allelic contigs. CONCLUSIONS: Purge Haplotigs improves the haploid and diploid representations of third-gen sequencing based genome assemblies by identifying and reassigning allelic contigs. The implementation is fast and scales well with large genomes, and it is less likely to over-purge repetitive or paralogous elements compared to alignment-only based methods. The software is available at https://bitbucket.org/mroachawri/purge_haplotigs under a permissive MIT licence.

Lung Stereotactic Body Radiation Therapy.

Lung stereotactic body radiation therapy (SBRT) is a novel and effective modality for treatment of early stage non-sail cell lung cancer (NSCLC), with expanding indications in locally advanced and metastatic disease. Herein, we will review current treatment recommendations for early stage NSCLC, detail treatment planning of SBRT, and discuss future directions.

Prophages: an integral but understudied component of the human microbiome.

Phages integrated into a bacterial genome - called prophages - continuously monitor the vigour of the host bacteria to determine when to escape the genome and to protect their host from other phage infections, and they may provide genes that promote bacterial growth. Prophages are essential to almost all microbiomes, including the human microbiome. However, most human microbiome studies have focused on bacteria, ignoring free and integrated phages, so we know little about how these prophages affect the human microbiome. To address this gap in our knowledge, we compared the prophages identified in 14 987 bacterial genomes isolated from human body sites to characterize prophage DNA in the human microbiome. Here, we show that prophage DNA is ubiquitous, comprising on average 1-5 % of each bacterial genome. The prophage content per genome varies with the isolation site on the human body, the health of the human and whether the disease was symptomatic. The presence of prophages promotes bacterial growth and sculpts the microbiome. However, the disparities caused by prophages vary throughout the body.

Silver-Doped Titanium Oxide Layers for Improved Photocatalytic Activity and Antibacterial Properties of Titanium Implants.

Titanium has a long history of clinical use, but the naturally forming oxide is not ideal for bacterial resistance. Anodization processes can modify the crystallinity, surface topography, and surface chemistry of titanium oxides. Anatase, rutile, and mixed phase oxides are known to exhibit photocatalytic activity (PCA)-driven bacterial resistance under UVA irradiation. Silver additions are reported to enhance PCA and reduce bacterial attachment. This study investigated the effects of silver-doping additions to three established anodization processes. Silver doping showed no significant influence on oxide crystallinity, surface topography, or surface wettability. Oxides from a sulfuric acid anodization process exhibited significantly enhanced PCA after silver doping, but silver-doped oxides produced from phosphoric-acid-containing electrolytes did not. Staphylococcus aureus attachment was also assessed under dark and UVA-irradiated conditions on each oxide. Each oxide exhibited a photocatalytic antimicrobial effect as indicated by significantly decreased bacterial attachment under UVA irradiation compared to dark conditions. However, only the phosphorus-doped mixed anatase and rutile phase oxide exhibited an additional significant reduction in bacteria attachment under UVA irradiation as a result of silver doping. The antimicrobial success of this oxide was attributed to the combination of the mixed phase oxide and higher silver-doping uptake levels.

Hybracter: Enabling Scalable, Automated, Complete and Accurate Bacterial Genome Assemblies.

Improvements in the accuracy and availability of long-read sequencing mean that complete bacterial genomes are now routinely reconstructed using hybrid (i.e. short- and long-reads) assembly approaches. Complete genomes allow a deeper understanding of bacterial evolution and genomic variation beyond single nucleotide variants (SNVs). They are also crucial for identifying plasmids, which often carry medically significant antimicrobial resistance (AMR) genes. However, small plasmids are often missed or misassembled by long-read assembly algorithms. Here, we present Hybracter which allows for the fast, automatic, and scalable recovery of near-perfect complete bacterial genomes using a long-read first assembly approach. Hybracter can be run either as a hybrid assembler or as a long-read only assembler. We compared Hybracter to existing automated hybrid and long-read only assembly tools using a diverse panel of samples of varying levels of long-read accuracy with manually curated ground truth reference genomes. We demonstrate that Hybracter as a hybrid assembler is more accurate and faster than the existing gold standard automated hybrid assembler Unicycler. We also show that Hybracter with long-reads only is the most accurate long-read only assembler and is comparable to hybrid methods in accurately recovering small plasmids.

Hybracter: enabling scalable, automated, complete and accurate bacterial genome assemblies.

Improvements in the accuracy and availability of long-read sequencing mean that complete bacterial genomes are now routinely reconstructed using hybrid (i.e. short- and long-reads) assembly approaches. Complete genomes allow a deeper understanding of bacterial evolution and genomic variation beyond single nucleotide variants. They are also crucial for identifying plasmids, which often carry medically significant antimicrobial resistance genes. However, small plasmids are often missed or misassembled by long-read assembly algorithms. Here, we present Hybracter which allows for the fast, automatic and scalable recovery of near-perfect complete bacterial genomes using a long-read first assembly approach. Hybracter can be run either as a hybrid assembler or as a long-read only assembler. We compared Hybracter to existing automated hybrid and long-read only assembly tools using a diverse panel of samples of varying levels of long-read accuracy with manually curated ground truth reference genomes. We demonstrate that Hybracter as a hybrid assembler is more accurate and faster than the existing gold standard automated hybrid assembler Unicycler. We also show that Hybracter with long-reads only is the most accurate long-read only assembler and is comparable to hybrid methods in accurately recovering small plasmids.

Hecatomb: an integrated software platform for viral metagenomics.

BACKGROUND: Modern sequencing technologies offer extraordinary opportunities for virus discovery and virome analysis. Annotation of viral sequences from metagenomic data requires a complex series of steps to ensure accurate annotation of individual reads and assembled contigs. In addition, varying study designs will require project-specific statistical analyses. FINDINGS: Here we introduce Hecatomb, a bioinformatic platform coordinating commonly used tasks required for virome analysis. Hecatomb means "a great sacrifice." In this setting, Hecatomb is "sacrificing" false-positive viral annotations using extensive quality control and tiered-database searches. Hecatomb processes metagenomic data obtained from both short- and long-read sequencing technologies, providing annotations to individual sequences and assembled contigs. Results are provided in commonly used data formats useful for downstream analysis. Here we demonstrate the functionality of Hecatomb through the reanalysis of a primate enteric and a novel coral reef virome. CONCLUSION: Hecatomb provides an integrated platform to manage many commonly used steps for virome characterization, including rigorous quality control, host removal, and both read- and contig-based analysis. Each step is managed using the Snakemake workflow manager with dependency management using Conda. Hecatomb outputs several tables properly formatted for immediate use within popular data analysis and visualization tools, enabling effective data interpretation for a variety of study designs. Hecatomb is hosted on GitHub (github.com/shandley/hecatomb) and is available for installation from Bioconda and PyPI.

Influence of connection design and material properties on stress distribution and fatigue lifetime of zygomatic implants: A finite element analysis.

Zygomatic implants (ZIs) were developed as a graftless alternative to rehabilitate severely reabsorbed maxillae. This study aims to employ three-dimensional finite element analysis (FEA) to simulate the impact of external hexagonal implant connection (EHC) and internal hexagonal implant connection (IHC) on the stress distribution and fatigue lifetime within the ZI systems using parameters defined in ISO 14801:2016. Two ZI assemblies (Nobel Biocare and Noris Medical) were scanned in a micro-CT scanner and reconstructed using Nrecon software. Three-dimensional models were generated by Simpleware ScanIP Medical software. All models were exported to FEA software (ABAQUS) and subsequently to a fatigue analysis software (Fe-safe). A compressive 150 N load was applied at a 40° angle on the cap surface. A 15 Hz frequency was applied in the in silico cyclic test. The implant components had material properties of commercially pure grade 4 titanium (CPTi) and Titanium-6Aluminum-4Vanadium alloy (Ti64). Von Mises stress data, contour plots, and fatigue limits were collected and analyzed. EHC models exhibited higher peak stresses in implant components for both materials compared to IHC models. However, simulated bone support results showed the opposite trend, with higher stresses on IHCthan EHC models. The fatigue analysis revealed that assemblies with both designs exceeded ISO 14801:2016 number of cycles limits using Ti64, while CPTi groups exhibited comparatively lower worst life-repeats. In conclusion, ZIs with IHC were found to have a more homogeneous and advantageous stress distribution within both materials tested. Ti64 demonstrates a prolonged service life for both design connections.

Bioenergetic mapping of 'healthy microbiomes' via compound processing potential imprinted in gut and soil metagenomes.

Despite mounting evidence of their importance in human health and ecosystem functioning, the definition and measurement of 'healthy microbiomes' remain unclear. More advanced knowledge exists on health associations for compounds used or produced by microbes. Environmental microbiome exposures (especially via soils) also help shape, and may supplement, the functional capacity of human microbiomes. Given the synchronous interaction between microbes, their feedstocks, and micro-environments, with functional genes facilitating chemical transformations, our objective was to examine microbiomes in terms of their capacity to process compounds relevant to human health. Here we integrate functional genomics and biochemistry frameworks to derive new quantitative measures of in silico potential for human gut and environmental soil metagenomes to process a panel of major compound classes (e.g., lipids, carbohydrates) and selected biomolecules (e.g., vitamins, short-chain fatty acids) linked to human health. Metagenome functional potential profile data were translated into a universal compound mapping 'landscape' based on bioenergetic van Krevelen mapping of function-level meta-compounds and corresponding functional relative abundances, reflecting imprinted genetic capacity of microbiomes to metabolize an array of different compounds. We show that measures of 'compound processing potential' associated with human health and disease (examining atherosclerotic cardiovascular disease, colorectal cancer, type 2 diabetes and anxious-depressive behavior case studies), and displayed seemingly predictable shifts along gradients of ecological disturbance in plant-soil ecosystems (three case studies). Ecosystem quality explained 60-92 % of variation in soil metagenome compound processing potential measures in a post-mining restoration case study dataset. With growing knowledge of the varying proficiency of environmental microbiota to process human health associated compounds, we might design environmental interventions or nature prescriptions to modulate our exposures, thereby advancing microbiota-oriented approaches to human health. Compound processing potential offers a simplified, integrative approach for applying metagenomics in ongoing efforts to understand and quantify the role of microbiota in environmental- and human-health.