The tidyomics ecosystem: Enhancing omic data analyses.

The growth of omic data presents evolving challenges in data manipulation, analysis, and integration. Addressing these challenges, Bioconductor1 provides an extensive community-driven biological data analysis platform. Meanwhile, tidy R programming2 offers a revolutionary standard for data organisation and manipulation. Here, we present the tidyomics software ecosystem, bridging Bioconductor to the tidy R paradigm. This ecosystem aims to streamline omic analysis, ease learning, and encourage cross-disciplinary collaborations. We demonstrate the effectiveness of tidyomics by analysing 7.5 million peripheral blood mononuclear cells from the Human Cell Atlas3, spanning six data frameworks and ten analysis tools.

The tidyomics ecosystem: enhancing omic data analyses.

The growth of omic data presents evolving challenges in data manipulation, analysis and integration. Addressing these challenges, Bioconductor provides an extensive community-driven biological data analysis platform. Meanwhile, tidy R programming offers a revolutionary data organization and manipulation standard. Here we present the tidyomics software ecosystem, bridging Bioconductor to the tidy R paradigm. This ecosystem aims to streamline omic analysis, ease learning and encourage cross-disciplinary collaborations. We demonstrate the effectiveness of tidyomics by analyzing 7.5 million peripheral blood mononuclear cells from the Human Cell Atlas, spanning six data frameworks and ten analysis tools.

Jugular venous flow dynamics during acute weightlessness.

During spaceflight, fluids shift headward, causing internal jugular vein (IJV) distension and altered hemodynamics, including stasis and retrograde flow, that may increase the risk of thrombosis. This study's purpose was to determine the effects of acute exposure to weightlessness (0-G) on IJV dimensions and flow dynamics. We used two-dimensional (2-D) ultrasound to measure IJV cross-sectional area (CSA) and Doppler ultrasound to characterize venous blood flow patterns in the right and left IJV in 13 healthy participants (6 females) while 1) seated and supine on the ground, 2) supine during 0-G parabolic flight, and 3) supine during level flight (at 1-G). On Earth, in 1-G, moving from seated to supine posture increased CSA in both left (+62 [95% CI: +42 to 81] mm2, P < 0.0001) and right (+86 [95% CI: +58 to 113] mm2, P < 0.00012) IJV. Entry into 0-G further increased IJV CSA in both left (+27 [95% CI: +5 to 48] mm2, P = 0.02) and right (+30 [95% CI: +0.3 to 61] mm2, P = 0.02) relative to supine in 1-G. We observed stagnant flow in the left IJV of one participant during 0-G parabolic flight that remained during level flight but was not present during any imaging during preflight measures in the seated or supine postures; normal venous flow patterns were observed in the right IJV during all conditions in all participants. Alterations to cerebral outflow dynamics in the left IJV can occur during acute exposure to weightlessness and thus, may increase the risk of venous thrombosis during any duration of spaceflight.NEW & NOTEWORTHY The absence of hydrostatic pressure gradients in the vascular system and loss of tissue weight during weightlessness results in altered flow dynamics in the left internal jugular vein in some astronauts that may contribute to an increased risk of thromboembolism during spaceflight. Here, we report that the internal jugular veins distend bilaterally in healthy participants and that flow stasis can occur in the left internal jugular vein during acute weightlessness produced by parabolic flight.

bootRanges: flexible generation of null sets of genomic ranges for hypothesis testing.

MOTIVATION: Enrichment analysis is a widely utilized technique in genomic analysis that aims to determine if there is a statistically significant association between two sets of genomic features. To conduct this type of hypothesis testing, an appropriate null model is typically required. However, the null distribution that is commonly used can be overly simplistic and may result in inaccurate conclusions. RESULTS: bootRanges provides fast functions for generation of block bootstrapped genomic ranges representing the null hypothesis in enrichment analysis. As part of a modular workflow, bootRanges offers greater flexibility for computing various test statistics leveraging other Bioconductor packages. We show that shuffling or permutation schemes may result in overly narrow test statistic null distributions and over-estimation of statistical significance, while creating new range sets with a block bootstrap preserves local genomic correlation structure and generates more reliable null distributions. It can also be used in more complex analyses, such as accessing correlations between cis-regulatory elements (CREs) and genes across cell types or providing optimized thresholds, e.g. log fold change (logFC) from differential analysis. AVAILABILITY AND IMPLEMENTATION: bootRanges is freely available in the R/Bioconductor package nullranges hosted at https://bioconductor.org/packages/nullranges.

matchRanges: generating null hypothesis genomic ranges via covariate-matched sampling.

MOTIVATION: Deriving biological insights from genomic data commonly requires comparing attributes of selected genomic loci to a null set of loci. The selection of this null set is non-trivial, as it requires careful consideration of potential covariates, a problem that is exacerbated by the non-uniform distribution of genomic features including genes, enhancers, and transcription factor binding sites. Propensity score-based covariate matching methods allow the selection of null sets from a pool of possible items while controlling for multiple covariates; however, existing packages do not operate on genomic data classes and can be slow for large data sets making them difficult to integrate into genomic workflows. RESULTS: To address this, we developed matchRanges, a propensity score-based covariate matching method for the efficient and convenient generation of matched null ranges from a set of background ranges within the Bioconductor framework. AVAILABILITY AND IMPLEMENTATION: Package: https://bioconductor.org/packages/nullranges, Code: https://github.com/nullranges, Documentation: https://nullranges.github.io/nullranges.

A Self-Help Manual for Psychological Distress and Quality of Life During a Haemopoietic Stem-Cell Transplant: An Effectiveness and Acceptability Pilot.

Haemopoietic stem-cell transplantation (HSCT) can be a highly distressing procedure that negatively impacts quality of life (QoL). Self-help interventions can help improve psychopathology and wellbeing in patients with physical illness, but have rarely been trialled with HSCT recipients. This study aimed to pilot the utility of a self-help manual intervention during the acute phase of HSCT. Forty autologous and allogeneic HSCT candidates were randomly assigned to a self-help manual intervention or treatment as usual (TAU). Psychological distress (BSI-18) and QoL (FACT-BMT-Vs4) were measured pre-, 2-3 weeks and 3 months post-HSCT. Linear mixed-effects analyses showed no significant group-time interaction for global QoL (p = .199) or global distress (p = .624). However, highlighting a protective role during admission, manual participants showed minimal QoL or somatic distress change at 2-3 weeks post-transplant compared with moderate-large effects for reduced QoL (d = 0.62) and increased somatic distress (d = - 0.81) for TAU patients. Thematic analysis suggests the manual helped prepare patients for transplant and provided strategies to improve distress and QoL. This pilot provides preliminary evidence for the benefit of a self-help manual during hospitalisation for a HSCT. More intensive, recovery-focussed care, however, may be needed to improve psychological health in the post-hospital period. Retrospectively registered trial (ANZCTR No. 12620001165976, 6th November 2020).

Provision of a Multidisciplinary Post-Suicidal, Community-Based Aftercare Program: A Longitudinal Study.

Suicide is a global concern with rates in Australia continuing to increase. Effective post-suicidal care is critical for reducing persistent suicidal behaviour. One model of care is that adopted by Alfred Health, delivering a multidisciplinary, hybrid clinical and non-clinical (psycho-social support), assertive outreach approach. This study measured improvements in resilience and wellbeing, changes to distress and suicidal ideation at least 6-months post-discharge from care. Thirty-one consumers participated including a one-on-one interview to gather qualitative feedback. There was a significant change on all outcome measures with large effect sizes. Participants had significantly reduced suicidal ideation and distress and increased coping self-efficacy, hope and well-being. The qualitative findings indicated that a key component to recovery was the staff. Limitations included a low sample size, and broad time range of follow-up data collection. Providing assertive, multidisciplinary, collaborative and outreach-focused post-suicidal care can increase and sustain protective psychological factors and reduced suicidal ideation in most individuals.

Long-term Cardiovascular Risk in Astronauts: Comparing NASA Mission Astronauts With a Healthy Cohort From the Cooper Center Longitudinal Study.

OBJECTIVE: To determine the long-term cardiovascular disease risk of astronauts with spaceflight exposure compared with a well-matched cohort. METHODS: National Aeronautics and Space Administration (NASA) astronauts are selected into their profession based upon education, unique skills, and health and are exposed to cardiovascular disease risk factors during spaceflight. The Cooper Center Longitudinal Study (CCLS) is a generally healthy cohort from a preventive medicine clinic in Dallas, Texas. Using a matched cohort design, astronauts who were selected beginning April 1, 1959, (and each subsequent selection class through 2009) and exposed to spaceflight were matched to CCLS participants who met astronaut selection criteria; 1514 CCLS participants matched to 303 astronauts in a 5-to-1 ratio on sex, date of birth, and age. The outcome of cardiovascular mortality through December 31, 2016, was determined by death certificate or National Death Index. RESULTS: There were 11 deaths caused by cardiovascular disease (CVD) among astronauts and 46 among CCLS participants. There was no evidence of increased mortality risk in astronauts (hazard ratio [HR]=1.10; 95% confidence interval [CI], 0.50 to 2.45) with adjustment for baseline cardiovascular covariates. However, the secondary outcome of CVD events showed an increased adjusted risk in astronauts (HR=2.41; 95% CI, 1.26 to 4.63). CONCLUSION: No increased risk of CVD mortality was observed in astronauts with spaceflight exposure compared with a well-matched cohort, but there was evidence of increased total CVD events. Given that the duration of spaceflight will increase, particularly on missions to Mars, continued surveillance and mitigation of CVD risk is needed to ensure the safety of those who venture into space.

Noninvasive indicators of intracranial pressure before, during, and after long-duration spaceflight.

Weightlessness induces a cephalad shift of blood and cerebrospinal fluid that may increase intracranial pressure (ICP) during spaceflight, whereas lower body negative pressure (LBNP) may provide an opportunity to caudally redistribute fluids and lower ICP. To investigate the effects of spaceflight and LBNP on noninvasive indicators of ICP (nICP), we studied 13 crewmembers before and after spaceflight in seated, supine, and 15° head-down tilt postures, and at ∼45 and ∼150 days of spaceflight with and without 25 mmHg LBNP. We used four techniques to quantify nICP: cerebral and cochlear fluid pressure (CCFP), otoacoustic emissions (OAE), ultrasound measures of optic nerve sheath diameter (ONSD), and ultrasound-based internal jugular vein pressure (IJVp). On flight day 45, two nICP measures were lower than preflight supine posture [CCFP: mean difference -98.5 -nL (CI: -190.8 to -6.1 -nL), P = 0.037]; [OAE: -19.7° (CI: -10.4° to -29.1°), P < 0.001], but not significantly different from preflight seated measures. Conversely, ONSD was not different than any preflight posture, whereas IJVp was significantly greater than preflight seated measures [14.3 mmHg (CI: 10.1 to 18.5 mmHg), P < 0.001], but not significantly different than preflight supine measures. During spaceflight, acute LBNP application did not cause a significant change in nICP indicators. These data suggest that during spaceflight, nICP is not elevated above values observed in the seated posture on Earth. Invasive measures would be needed to provide absolute ICP values and more precise indications of ICP change during various phases of spaceflight.NEW & NOTEWORTHY The current study provides new evidence that intracranial pressure (ICP), as assessed with noninvasive measures, may not be elevated during long-duration spaceflight. In addition, the acute use of lower body negative pressure did not significantly reduce indicators of ICP during weightlessness.

Corrigendum to 'A transcriptomic dataset evaluating the effect of radiotherapy injury on cells of skin and soft tissue' Data in Brief 41 (2022) 107828.

[This corrects the article DOI: 10.1016/j.dib.2022.107828.].

A transcriptomic dataset evaluating the effect of radiotherapy injury on cells of skin and soft tissue.

Radiotherapy injury to cells of the skin and subcutaneous tissue is an inevitable consequence of external beam radiation for treatment of cancer. This sublethal injury to normal tissues plays a significant role in the development of fibrosis, lymphedema, impaired wound healing, and recurrent infections. To elucidate the transcriptional changes that occur in cells of the skin and soft tissues after radiotherapy injury, we performed genome-wide RNA-sequencing comparing irradiated cells (10Gy) with non-irradiated (0Gy) controls in normal human dermal fibroblasts, normal human keratinocytes, human microvascular endothelial cells, human dermal lymphatic endothelial cells, pericytes and adipose derived stem cell populations. These data are publicly available from the Gene Expression Omnibus database (accession number GSE184119). Further insights can be gained by comparing the mRNA signatures arising from radiation injury derived from these data to publicly available signatures from other studies involving similar or different tissue types. These global targets hold potential for manipulation to mitigate radiotherapy soft tissue injury.

Psychosis and Hopelessness Mediate the Relationship Between Reduced Sleep and Suicidal Ideation in Schizophrenia Spectrum Disorders.

OBJECTIVE: Suicide is a major cause of death amongst individuals with schizophrenia spectrum disorders (SSD). Despite numerous risk factors being identified, accurate prediction of suicidality and provision of tailored and effective treatment is difficult. One factor that may warrant particular attention as a contributor to increased psychopathology and suicidality in SSD is disturbed sleep. Sleep disturbances have been reliably linked to greater levels of suicidal ideation and are highly prevalent amongst individuals with SSD. This study aimed to examine if reduced sleep duration and psychopathology are associated with increased suicidal ideation. METHOD: One-hundred and eighteen adults with chronic SSD living within the community participated in this cross-sectional study. Psychosis symptoms were assessed using the Positive and Negative Syndrome Scale. Items 4 and 10 from the Montgomery-Asperg Depression Rating Scale and Item 2 from the Calgary Depression Scale for Schizophrenia were used to assess reduced sleep duration, current suicidal ideation, and hopelessness, respectively. All measures were rated concurrently. RESULTS: A hierarchical logistic regression revealed that greater acute sleep disturbances were associated with increased suicidal ideation and this relationship was found to be uniquely mediated by both positive symptom severity and hopelessness. CONCLUSION: These results suggest that individuals with SSD who exhibited disrupted or disordered sleep, positive symptoms and/or hopelessness should be routinely screened for suicidal thinking. Furthermore, interventions that effectively target sleep disruptions may provide much-needed action against suicidal ideation.HIGHLIGHTSReduced sleep found to be associated with increased suicidal ideationThis was uniquely mediated by both hopelessness and positive symptomsMore regular screening of sleep problems in schizophrenia is needed.

The impact of telemedicine enabled pre-hospital triage in acute stroke - a protocol for a mixed methods systematic review.

Introduction: Increasing access to thrombolysis and thrombectomy through improved pathway organisation remains a health service challenge that requires contextualisation to the geographic, demographic and resourcing status of any regional stroke service. Pre-hospital delays or delays during inter-hospital transfers can result in patients being outside the window for one or both interventions. Pre-hospital triage using technology-enabled interdisciplinary communication networks may facilitate rapid individualized care decisions, permitting streamlined care pathways to hospital sites most appropriate to their clinical presentation and history in the first instance. Understanding the experience of those involved in efforts to improve or reorganise care may help to explain the impact observed. Objectives: 1. To review the impact of pre-hospital telemedicine enabled workflow intervention strategies on patient outcomes and on service process metrics in hyper-acute stroke care2. To examine how the experience of those involved in providing or receiving such interventions might identify key characteristics of effective interventions. Inclusion criteria: Quantitative, qualitative and primary mixed methods studies will be included. Quantitative studies will assess effectiveness of telemedicine-enabled interventions that facilitate pre-hospital acute stroke triage. Intervention effects on functional outcomes of patients, on intervention rates and on key time metrics in hyperacute stroke care will be assessed. Qualitative studies will explore the experiences of people involved in or impacted by these interventions. Methods and analysis: A convergent segregated mixed methods systematic review will synthesise and integrate primary qualitative, quantitative and mixed methods studies using the Joanna Briggs Institute methodology. Database searches will include OVID (MEDLINE), EMBASE, The Cochrane Library, CINAHL and Web of Science. Critical appraisal will include the Mixed Methods Assessment Tool. Results of quantitative studies and findings of qualitative studies will be integrated and configured to explore and contextualize each single method synthesis. Systematic review registration: This protocol has been submitted for registration with PROSPERO.

Transcriptomic Responses and Survival Mechanisms of Staphylococci to the Antimicrobial Skin Lipid Sphingosine.

Sphingosines are antimicrobial lipids that form part of the innate barrier to skin colonization by microbes. Sphingosine deficiencies can result in increased epithelial infections by bacteria including Staphylococcus aureus. Recent studies have focused on the potential use of sphingosine resistance or its potential mechanisms. We used RNA-Seq to identify the common d-sphingosine transcriptomic response of the transient skin colonizer S. aureus and the dominant skin coloniser S. epidermidis. A common d-sphingosine stimulon was identified that included downregulation of the SaeSR two-component system (TCS) regulon and upregulation of both the VraSR TCS and CtsR stress regulons. We show that the PstSCAB phosphate transporter, and VraSR offer intrinsic resistance to d-sphingosine. Further, we demonstrate increased sphingosine resistance in these staphylococci evolves readily through mutations in genes encoding the FarE-FarR efflux/regulator proteins. The ease of selecting mutants with resistance to sphingosine may impact upon staphylococcal colonization of skin where the lipid is present and have implications with topical therapeutic applications.

How the experience of different non-acute bed-based mental health services reinforces the need for tailored stepped care.

Objective Stepped care as a model of provision of mental health services has been frequently described from clinical or health administration perspectives, but less is known about the consumer perspective of stepped models of care. Method Qualitative interviews were undertaken with 18 consumers across a range of residential mental health services in Melbourne, Australia. Interviews were designed to help understand consumers' needs and experiences in navigating different services to meet their needs at different times in their mental health journey. Results Consumers experience fluctuations in their mental state that are best responded to by having access to a range of services, as well as to services that can respond flexibly to changing needs. Consumers do not necessarily progress through stepped care in a linear or step-up, step-down fashion. Conclusion Stepped care services need to be flexible in accommodating people along a continuum of care and responsive to where the consumer is at on their journey, rather than predetermining the trajectory of care. What is known about the topic? Stepped care has been identified as a critical component of comprehensive mental health care, bridging the gap between primary care and acute mental health services. The components of effective stepped care models have been broadly articulated, but the experience of moving through different components of care in response to changing needs has not previously been well described. What does the paper add? This paper presents consumer perspectives on a model of stepped care that is designed to respond flexibly to the changing needs of consumers, rather than representing a linear model of progress through the system. What are the implications for practitioners? Mental health services are increasingly grappling with provision of care to the 'missing middle': people with chronic mental illness yet not in an acute phase requiring in-patient hospital care. This paper presents a model of stepped care that responds to the fluctuating needs of consumers.

CTCF: an R/bioconductor data package of human and mouse CTCF binding sites.

Summary: CTCF (CCCTC-binding factor) is an 11-zinc-finger DNA binding protein which regulates much of the eukaryotic genome's 3D structure and function. The diversity of CTCF binding motifs has led to a fragmented landscape of CTCF binding data. We collected position weight matrices of CTCF binding motifs and defined strand-oriented CTCF binding sites in the human and mouse genomes, including the recent Telomere to Telomere and mm39 assemblies. We included selected experimentally determined and predicted CTCF binding sites, such as CTCF-bound cis-regulatory elements from SCREEN ENCODE. We recommend filtering strategies for CTCF binding motifs and demonstrate that liftOver is a viable alternative to convert CTCF coordinates between assemblies. Our comprehensive data resource and usage recommendations can serve to harmonize and strengthen the reproducibility of genomic studies utilizing CTCF binding data. Availability and implementation: https://bioconductor.org/packages/CTCF. Companion website: https://dozmorovlab.github.io/CTCF/; Code to reproduce the analyses: https://github.com/dozmorovlab/CTCF.dev. Supplementary information: Supplementary data are available at Bioinformatics Advances online.

Novel application of metagenomics for the strain-level detection of bacterial contaminants within non-sterile industrial products - a retrospective, real-time analysis.

The home and personal care (HPC) industry generally relies on initial cultivation and subsequent biochemical testing for the identification of microorganisms in contaminated products. This process is slow (several days for growth), labour intensive, and misses organisms which fail to revive from the harsh environment of preserved consumer products. Since manufacturing within the HPC industry is high-throughput, the process of identification of microbial contamination could benefit from the multiple cultivation-independent methodologies that have developed for the detection and analysis of microbes. We describe a novel workflow starting with automated DNA extraction directly from a HPC product, and subsequently applying metagenomic methodologies for species and strain-level identification of bacteria. The workflow was validated by application to a historic microbial contamination of a general-purpose cleaner (GPC). A single strain of Pseudomonas oleovorans was detected metagenomically within the product. The metagenome mirrored that of a contaminant isolated in parallel by a traditional cultivation-based approach. Using a dilution series of the incident sample, we also provide evidence to show that the workflow enables detection of contaminant organisms down to 100 CFU/ml of product. To our knowledge, this is the first validated example of metagenomics analysis providing confirmatory evidence of a traditionally isolated contaminant organism, in a HPC product.

Bellagio II Report: Terrestrial Applications of Space Medicine Research.

AbstractINTRODUCTION: For over 50 yr, investigators have studied the physiological adaptations of the human system during short- and long-duration spaceflight exposures. Much of the knowledge gained in developing health countermeasures for astronauts onboard the International Space Station demonstrate terrestrial applications. To date, a systematic process for translating these space applications to terrestrial human health has yet to be defined.METHODS: In the summer of 2017, a team of 38 international scientists launched the Bellagio ll Summit Initiative. The goals of the Summit were: 1) To identify space medicine findings and countermeasures with highest probability for future terrestrial applications; and 2) To develop a roadmap for translation of these countermeasures to future terrestrial application. The team reviewed public domain literature, NASA databases, and evidence books within the framework of the five-stage National Institutes of Health (NIH) translation science model, and the NASA two-stage translation model. Teams then analyzed and discussed interdisciplinary findings to determine the most significant evidence-based countermeasures sufficiently developed for terrestrial application.RESULTS: Teams identified published human spaceflight research and applied translational science models to define mature products for terrestrial clinical practice.CONCLUSIONS: The Bellagio ll Summit identified a snapshot of space medicine research and mature science with the highest probability of translation and developed a Roadmap of terrestrial application from space medicine-derived countermeasures. These evidence-based findings can provide guidance regarding the terrestrial applications of best practices, countermeasures, and clinical protocols currently used in spaceflight.Sides MB, Johnston SL III, Sirek A, Lee PH, Blue RS, Antonsen EL, Basner M, Douglas GL, Epstein A, Flynn-Evans EE, Gallagher MB, Hayes J, Lee SMC, Lockley SW, Monseur B, Nelson NG, Sargsyan A, Smith SM, Stenger MB, Stepanek J, Zwart SR; Bellagio II Team. Bellagio II report: terrestrial applications of space medicine research. Aerosp Med Hum Perform. 2021; 92(8):650669.