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As next-generation sequencing technologies produce deeper genome coverages at lower costs, there is a critical need for reliable computational host DNA removal in metagenomic data. We find that insufficient host filtration using prior human genome references can introduce false sex biases and inadvertently permit flow-through of host-specific DNA during bioinformatic analyses, which could be exploited for individual identification. To address these issues, we introduce and benchmark three host filtration methods of varying throughput, with concomitant applications across low biomass samples such as skin and high microbial biomass datasets including fecal samples. We find that these methods are important for obtaining accurate results in low biomass samples (e.g., tissue, skin). Overall, we demonstrate that rigorous host filtration is a key component of privacy-minded analyses of patient microbiomes and provide computationally efficient pipelines for accomplishing this task on large-scale datasets.

In 2020, we identified cancer-specific microbial signals in The Cancer Genome Atlas (TCGA) [1]. Multiple peer-reviewed papers independently verified or extended our findings [2-12]. Given this impact, we carefully considered concerns by Gihawi et al. [13] that batch correction and database contamination with host sequences artificially created the appearance of cancer type-specific microbiomes. (1) We tested batch correction by comparing raw and Voom-SNM-corrected data per-batch, finding predictive equivalence and significantly similar features. We found consistent results with a modern microbiome-specific method (ConQuR [14]), and when restricting to taxa found in an independent, highly-decontaminated cohort. (2) Using Conterminator [15], we found low levels of human contamination in our original databases (~1% of genomes). We demonstrated that the increased detection of human reads in Gihawi et al. [13] was due to using a newer human genome reference. (3) We developed Exhaustive, a method twice as sensitive as Conterminator, to clean RefSeq. We comprehensively host-deplete TCGA with many human (pan)genome references. We repeated all analyses with this and the Gihawi et al. [13] pipeline, and found cancer type-specific microbiomes. These extensive re-analyses and updated methods validate our original conclusion that cancer type-specific microbial signatures exist in TCGA, and show they are robust to methodology.

Abstract As next-generation sequencing technologies produce deeper genome coverages at lower costs, there is a critical need for reliable computational host DNA removal in metagenomic data. We find that insufficient host filtration using prior human genome references can introduce false sex biases and inadvertently permit flow-through of host-specific DNA during bioinformatic analyses, which could be exploited for individual identification. To address these issues, we introduce and benchmark three host filtration methods of varying throughput, with concomitant applications across low biomass samples such as skin and high microbial biomass datasets including fecal samples. We find that these methods are important for obtaining accurate results in low biomass samples (e.g., tissue, skin). Overall, we demonstrate that rigorous host filtration is a key component of privacy-minded analyses of patient microbiomes and provide computationally efficient pipelines for accomplishing this task on large-scale datasets.

Background: Members of racial or ethnic minority groups utilize palliative care (PC) services less than non-Hispanic White patients and multiple factors contribute to this disparity. The impact of racial, ethnic, and language (REL) concordance between patients and clinicians has been demonstrated in general medical populations, but not in PC populations. We characterized the racial and ethnic composition and languages spoken of California PC clinicians and patients to examine clinical impacts of REL concordance. Methods: Using Palliative Care Quality Network data, 15 inpatient teams were identified in California that had collected data on patient race/ethnicity and language. Patient and clinician data were analyzed using means and medians for continuous variables, and chi-squared tests to explore similarities and differences between clinician and patient data. Results: 51 clinicians from nine teams completed the survey. The largest non-White and non-English speaking groups among patients and clinicians identified as Hispanic/Latinx (31.5% of patients, 16.3% of clinicians) and as Spanish speakers (22.6% of patients, 7.5% of clinicians). There was a significantly higher proportion of Hispanic/Latinx patients compared to clinicians (p-value 0.01), with Southern California demonstrating the largest difference (30.4% of patients vs. 10.7 % of clinicians, p-value 0.01). Similar proportions of patients and clinicians reported Spanish fluency (22.6% vs 27.5%, p-value 0.31). Discussion: We found significant differences in the racial/ethnic distributions of Hispanic/Latinx patients and clinicians in California, prompting consideration of whether a lack of representation of Hispanic/Latinx clinicians relative to the patient population may contribute to lower palliative care utilization among Hispanic/Latinx patients.

Cancers rely on multiple, heterogeneous processes at different scales, pertaining to many biomedical fields. Therefore, understanding cancer is necessarily an interdisciplinary task that requires placing specialised experimental and clinical research into a broader conceptual, theoretical, and methodological framework. Without such a framework, oncology will collect piecemeal results, with scant dialogue between the different scientific communities studying cancer. We argue that one important way forward in service of a more successful dialogue is through greater integration of applied sciences (experimental and clinical) with conceptual and theoretical approaches, informed by philosophical methods. By way of illustration, we explore six central themes: (i) the role of mutations in cancer; (ii) the clonal evolution of cancer cells; (iii) the relationship between cancer and multicellularity; (iv) the tumour microenvironment; (v) the immune system; and (vi) stem cells. In each case, we examine open questions in the scientific literature through a philosophical methodology and show the benefit of such a synergy for the scientific and medical understanding of cancer.

Physical disturbances typically cause ecological impacts within areas of direct contact (primary disturbances) but can also impact surrounding areas through other mechanisms (secondary disturbances). Secondary disturbances are often overlooked, especially in marine ecosystems where sufficiently detailed observation can be difficult to obtain. For example, boat moorings create circular clearings in seagrass meadows by physically scouring the seabed, but visible impacts extend beyond this into surrounding areas due to disturbances such as increased sediment transport, edge effects, and shading from boats. Previous studies on impacts of moorings have not distinguished between primary and secondary disturbances, and secondary disturbances are rarely accounted for in environmental management. We used spatial modelling to examine the primary and secondary disturbances associated with moorings in a meadow of the threatened seagrass Posidonia australis. We compared the disturbance from traditional ‘swing’ moorings with ‘environmentally friendly’ moorings (EFM) designed to reduce scour. Within the scour zone (0-5 m from moorings), we compared seagrass cover around swing moorings with cover around EFM. Further from moorings (5-25 m), we tested the degree of association between seagrass cover and secondary disturbances that may accumulate with mooring density and be influenced by mooring design. We found that mooring design affected the degree of direct disturbance, with cover of P. australis in the scour zone of standard moorings ~49% lower than that of EFMs (p < 0.01). Mooring density had cumulative negative effects on P. australis cover in the surrounding meadow, but the influence of mooring density was reduced when most moorings were EFMs. This suggests that secondary effects contingent on direct physical disturbance (e.g. sediment transport, fragmentation, edge effects) may be stronger than the general influence of moored boats (shading). We use the findings to simulate two broad policy scenarios for mooring designs in P. australis meadows: installing only EFM, or only traditional moorings. The simulations suggest that using only EFM would lead to a 14.2% increase (~164 m2), whereas installing only traditional moorings would lead to a 16% (~187 m2) loss of P. australis cover in this already highly disturbed meadow. Synthesis and applications: We demonstrate a nondestructive approach to assessing primary and secondary disturbances driving the distribution of a threatened seagrass and simulate a range of potential management scenarios that could assist in conserving the species.

ABSTRACT The polewards range expansion of tropical herbivorous fish into temperate latitudes is leading to overgrazing of marine habitats and community phase shifts in some regions. Here, we test the potential effects of increased herbivory on the temperate habitat‐forming seagrass Posidonia australis. We used a series of simulated herbivory experiments to predict the potential impacts of climate‐mediated increases in seagrass consumption along P. australis entire latitudinal range (~9° latitude) in eastern Australia (1700 km of coastline). We subjected treatment plots to two levels of simulated herbivory (10% or 80% of leaves clipped) and compared them to unclipped controls. We measured seagrass leaf growth rates and tissue chemical traits: carbohydrates in rhizomes, leaf phenolics, and nutrients (carbon, nitrogen, and C:N ratio) in leaves and rhizomes. At the warmest range‐edge population, we also tested how responses to increased herbivory may vary between summer and winter, or with repeated clipping events. Clipped shoots maintained growth rates similar to unclipped controls despite losing up to 80% of leaf biomass. This was consistent along the full latitudinal range and after repeated simulated herbivory at the northernmost location. One‐off clipping events impacted plant architecture, increasing the number of subdividing shoots. At the species range edge, leaves grew more in winter than in summer, and clipping tended to lower seagrass growth only in winter; however, higher levels of shoot subdivision were produced over summer than in winter. Plant chemical traits could not explain consistently the growth patterns observed despite some traits varying with latitude (e.g., leaf nitrogen content decreased with latitude and C:N ratio increased) and/or simulated herbivory. Synthesis: P. australis growth is not affected by increases in simulated herbivory and may be relatively resilient to future increases in seagrass consumption, suggesting that this species could be a relative ‘winner’ under future climate change conditions that lead to enhanced herbivory.

Periodontal disease is more common in individuals with rheumatoid arthritis (RA) who have detectable anti-citrullinated protein antibodies (ACPAs), implicating oral mucosal inflammation in RA pathogenesis. Here, we performed paired analysis of human and bacterial transcriptomics in longitudinal blood samples from RA patients. We found that patients with RA and periodontal disease experienced repeated oral bacteremias associated with transcriptional signatures of ISG15+HLADRhi and CD48highS100A2pos monocytes, recently identified in inflamed RA synovia and blood of those with RA flares. The oral bacteria observed transiently in blood were broadly citrullinated in the mouth, and their in situ citrullinated epitopes were targeted by extensively somatically hypermutated ACPAs encoded by RA blood plasmablasts. Together, these results suggest that (i) periodontal disease results in repeated breaches of the oral mucosa that release citrullinated oral bacteria into circulation, which (ii) activate inflammatory monocyte subsets that are observed in inflamed RA synovia and blood of RA patients with flares and (iii) activate ACPA B cells, thereby promoting affinity maturation and epitope spreading to citrullinated human antigens.

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.

Nipple–areolar complex (NAC) necrosis is a devastating complication in nipple-sparing mastectomies (NSMs) that significantly impacts patient's quality of life. The use of fluorescence angiography for intraoperative assessment of mastectomy skin flap perfusion in NSM has been successfully described and can be utilized to help guide surgical decision-making. Recently, a novel fluorescence-guided surgical imager was developed, OnLume Avata System (OnLume Surgical, Madison, WI), which provides intraoperative evaluation of vascular perfusion in ambient light. In this case report, we describe the use of OnLume fluorescence-guided surgery technology to help aid in clinical decision-making for two breast reconstruction cases with concern for intraoperative nipple hypoperfusion.

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.

Background:. Plastic and reconstructive surgery is one of the most competitive residency programs, and given the increased number of applicants for a relatively fixed number of positions, successfully matching is a challenge. Match rates have declined since 2018, with a match rate of ~55% in 2022. Two common options before reapplying are a preliminary year of residency (preliminary year) or a research fellowship. This study investigated which option is more beneficial for reapplicants seeking a successful match. Methods:. This retrospective study included all applicants to an integrated plastic and reconstructive surgery residency from 2015 to 2023. Two cohorts based on reapplication strategy (research fellowship or preliminary year) were created. Demographic, applicant, and match data were collected. Pearson chi-squared, Fisher exact, and Wilcoxon rank sum testing were performed. Results:. In total, 125 reapplicants were included. Seventy-one (56.8%) reapplicants pursued a preliminary year, and 29 (23.2%) completed a research fellowship. Research fellowship reapplicants had a greater mean number of first author publications (8.8 versus 3.2, P < 0.001), non-first author publications (11.3 versus 5.9, P = 0.021), poster presentations (9.7 versus 6.0, P = 0.028), and oral presentations (11.8 versus 6.4, P

Abstract Eco‐evolutionary experiments are typically conducted in semi‐unnatural controlled settings, such as mesocosms; yet inferences about how evolution and ecology interact in the real world would surely benefit from experiments in natural uncontrolled settings. Opportunities for such experiments are rare but do arise in the context of restoration ecology—where different “types” of a given species can be introduced into different “replicate” locations. Designing such experiments requires wrestling with consequential questions. (Q1) Which specific “types” of a focal species should be introduced to the restoration location? (Q2) How many sources of each type should be used—and should they be mixed together? (Q3) Which specific source populations should be used? (Q4) Which type(s) or population(s) should be introduced into which restoration sites? We recently grappled with these questions when designing an eco‐evolutionary experiment with threespine stickleback (Gasterosteus aculeatus) introduced into nine small lakes and ponds on the Kenai Peninsula in Alaska that required restoration. After considering the options at length, we decided to use benthic versus limnetic ecotypes (Q1) to create a mixed group of colonists from four source populations of each ecotype (Q2), where ecotypes were identified based on trophic morphology (Q3), and were then introduced into nine restoration lakes scaled by lake size (Q4). We hope that outlining the alternatives and resulting choices will make the rationales clear for future studies leveraging our experiment, while also proving useful for investigators considering similar experiments in the future.

Abstract 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 Gavert, Jason E. Stajich, Guy Amit, Antonio González, Stephen Wandro, Gili Perry, Ruthie Ariel, Arnon Meltser, Justin P. Shaffer, Qiyun Zhu, Nora Balint-Lahat, Iris Barshack, Maya Dadian, Einav N. Gal-Yam, Sandip P. Pate, Amir Bashan, Austin D. Swafford, Yitzhak Pilpel, Rob Knight, Ravid Straussman. Pan-cancer characterization of the tumor mycobiome and its clinical effects [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 3054.

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.

Six new species of Ampeliscidae are described: Ampelisca capella sp. nov., Ampelisca mingela sp. nov., Byblis pialba sp. nov. and Byblis wadara sp. nov. from the Great Barrier Reef; Ampelisca katoomba sp. nov. from the New South Wales shelf; and Byblis liena sp. nov. from the Queensland slope. Byblisoides esferis J. L. Barnard, 1961 is recorded from southeastern Australia, the first record of the genus in Australia. These bring the number of eastern Australian species to twenty-six. Distributions of three other species are extended northwards into Queensland. A key to all eastern Australian species is provided.

The presence and role of microbes in human cancers has come full circle in the last century. Tumors are no longer considered aseptic, but implications for cancer biology and oncology remain underappreciated. Opportunities to identify and build translational diagnostics, prognostics, and therapeutics that exploit cancer's second genome-the metagenome-are manifold, but require careful consideration of microbial experimental idiosyncrasies that are distinct from host-centric methods. Furthermore, the discoveries of intracellular and intra-metastatic cancer bacteria necessitate fundamental changes in describing clonal evolution and selection, reflecting bidirectional interactions with non-human residents. Reconsidering cancer clonality as a multispecies process similarly holds key implications for understanding metastasis and prognosing therapeutic resistance while providing rational guidance for the next generation of bacterial cancer therapies. Guided by these new findings and challenges, this Review describes opportunities to exploit cancer's metagenome in oncology and proposes an evolutionary framework as a first step towards modeling multispecies cancer clonality. Also see the video abstract here: https://youtu.be/-WDtIRJYZSs.

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, which is limited in feature resolution. To solve these challenges, we introduce operational genomic units (OGUs), which are the individual reference genomes derived from sequence alignment results, without further assigning them taxonomy. The OGU method advances current read-based metagenomics in two dimensions: (i) providing maximal resolution of community composition and (ii) permitting use of phylogeny-aware tools. Our analysis of real-world data sets shows that it is advantageous over currently adopted metagenomic analysis methods and the finest-grained 16S rRNA analysis methods in predicting biological traits. We thus propose the adoption of OGUs as an effective practice in metagenomic studies.

The unexpected roles of the microbiota in cancer challenge explanations of carcinogenesis that focus on tumor-intrinsic properties. Most tumors contain bacteria and viruses, and the host's proximal and distal microbiota influence both cancer incidence and therapeutic responsiveness. Continuing the history of cancer-microbe research, these findings raise a key question: to what extent is the microbiota relevant for clinical oncology? We approach this by critically evaluating three issues: how the microbiota provides a predictive biomarker of cancer growth and therapeutic responsiveness, the microbiota's causal role(s) in cancer development, and how therapeutic manipulations of the microbiota improve patient outcomes in cancer. Clarifying the conceptual and empirical aspects of the cancer-associated microbiota can orient future research and guide its implementation in clinical oncology.

Genome-wide association studies (GWAS) identify genetic variants associated with a trait, regardless of how those variants are associated with the outcome. Characterizing whether variants for psychiatric outcomes operate via specific versus general pathways provides more informative measures of genetic risk. In the current analysis, we used multivariate GWAS to tease apart variants associated with problematic alcohol use (ALCP-total) through either a shared risk for externalizing (EXT) or a problematic alcohol use-specific risk (ALCP-specific). SNPs associated with ALCP-specific were primarily related to alcohol metabolism. Genetic correlations showed ALCP-specific was predominantly associated with alcohol use and other forms of psychopathology, but not other forms of substance use. Polygenic scores for ALCP-total were associated with multiple forms of substance use, but polygenic scores for ALCP-specific were only associated with alcohol phenotypes. Polygenic scores for both ALCP-specific and EXT show different patterns of associations with alcohol misuse across development. Our results demonstrate that focusing on both shared and specific risk can better characterize pathways of risk for substance use disorders. Parsing risk pathways will become increasingly relevant as genetic information is incorporated into clinical practice.

The pursuit of highly sensitive and specific cancer diagnostics based on cell-free (cf) nucleic acids isolated from minimally invasive liquid biopsies has been an area of intense research and commercial effort for at least two decades. Most of these tests detect cancer-specific mutations or epigenetic modifications on circulating DNA derived from tumor cells (ctDNA). Although recent FDA approvals of both single and multi-analyte liquid biopsy companion diagnostic assays are proof of the tremendous progress made in this domain, using ctDNA for the diagnosis of early-stage (stage I/II) cancers remains challenging due to several factors, such as low mutational allele frequency in circulation, overlapping profiles in genomic alterations among diverse cancers, and clonal hematopoiesis. This review discusses these analytical challenges, interim solutions, and the opportunity to complement ctDNA diagnostics with microbiome-aware analyses that may mitigate several existing ctDNA assay limitations.

The emergence of magnetism in quantum materials creates a platform to realize spin-based applications in spintronics, magnetic memory, and quantum information science. A key to unlocking new functionalities in these materials is the discovery of tunable coupling between spins and other microscopic degrees of freedom. We present evidence for interlayer magnetophononic coupling in the layered magnetic topological insulator MnBi2Te4. Employing magneto-Raman spectroscopy, we observe anomalies in phonon scattering intensities across magnetic field-driven phase transitions, despite the absence of discernible static structural changes. This behavior is a consequence of a magnetophononic wave-mixing process that allows for the excitation of zone-boundary phonons that are otherwise 'forbidden' by momentum conservation. Our microscopic model based on density functional theory calculations reveals that this phenomenon can be attributed to phonons modulating the interlayer exchange coupling. Moreover, signatures of magnetophononic coupling are also observed in the time domain through the ultrafast excitation and detection of coherent phonons across magnetic transitions. In light of the intimate connection between magnetism and topology in MnBi2Te4, the magnetophononic coupling represents an important step towards coherent on-demand manipulation of magnetic topological phases.