A new genomic blueprint of the human gut microbiota.

The composition of the human gut microbiota is linked to health and disease, but knowledge of individual microbial species is needed to decipher their biological roles. Despite extensive culturing and sequencing efforts, the complete bacterial repertoire of the human gut microbiota remains undefined. Here we identify 1,952 uncultured candidate bacterial species by reconstructing 92,143 metagenome-assembled genomes from 11,850 human gut microbiomes. These uncultured genomes substantially expand the known species repertoire of the collective human gut microbiota, with a 281% increase in phylogenetic diversity. Although the newly identified species are less prevalent in well-studied populations compared to reference isolate genomes, they improve classification of understudied African and South American samples by more than 200%. These candidate species encode hundreds of newly identified biosynthetic gene clusters and possess a distinctive functional capacity that might explain their elusive nature. Our work expands the known diversity of uncultured gut bacteria, which provides unprecedented resolution for taxonomic and functional characterization of the intestinal microbiota.

A smartphone app effectively facilitates mothers' mind-mindedness: A randomized controlled trial.

The efficacy of a smartphone app intervention (BabyMind©) in facilitating mind-mindedness was investigated in a randomized controlled trial, assigning mothers and their 6-month-olds (N = 152; 72 girls, 146 White) to intervention or active control conditions. Mothers who had received the BabyMind© app intervention scored higher for appropriate (d = .61, 95% CI .28, .94) and lower for non-attuned (d = -.55, 95% CI -.92, -.18) mind-related comments at follow-up (age 12 months), compared with their control group counterparts. Adjusting for missing data did not alter this pattern of findings. Mothers' baseline parental reflective functioning did not moderate these relations. Results are discussed in terms of the benefits of early intervention and exploring the efficacy of the app in more diverse populations.

The InterPro protein families and domains database: 20 years on.

The InterPro database (https://www.ebi.ac.uk/interpro/) provides an integrative classification of protein sequences into families, and identifies functionally important domains and conserved sites. InterProScan is the underlying software that allows protein and nucleic acid sequences to be searched against InterPro's signatures. Signatures are predictive models which describe protein families, domains or sites, and are provided by multiple databases. InterPro combines signatures representing equivalent families, domains or sites, and provides additional information such as descriptions, literature references and Gene Ontology (GO) terms, to produce a comprehensive resource for protein classification. Founded in 1999, InterPro has become one of the most widely used resources for protein family annotation. Here, we report the status of InterPro (version 81.0) in its 20th year of operation, and its associated software, including updates to database content, the release of a new website and REST API, and performance improvements in InterProScan.

Can We Prevent Depression in At-Risk Older Adults Using Self-Help? The UK SHARD Trial of Behavioral Activation.

BACKGROUND: Treatment of established depression is the dominant approach to care of older adults, but prevention holds much promise. Self-help interventions are a feasible preventive approach, since they are scalable and low cost. There are few trials in this area. Behavioral Activation (BA) is a credible candidate psychological approach, which has been shown to work in therapist led care but not been trialled in a self-help form. AIM: To test the effectiveness of an unguided self-help intervention based on BA for older adults. METHODS: We compared a self-help intervention based on BA for older people (n = 172) to usual care (n = 160) in a pragmatic randomized controlled trial. Outcomes were depression status and severity (PHQ9) and health related quality of life (SF12). The primary timepoint of the primary outcome was depression at 4 months, with longer term follow up at 12 months to test sustained impact of the primary outcome. RESULTS: At 4 months adjusted PHQ-9 scores for BA self-help were 0.79 lower (95% CI: -1.70 to 0.13; p = 0.09) and the proportion of participants with case-level depression was significantly reduced (BA 31/137 (22.6%) versus usual care 41/141 (29.1%); Odds Ratio 0.48; 95% CI: 0.26-0.92; p = 0.03). There was no PHQ-9 difference at 12 months or for health related quality of life at any point (4 or 12 months). DISCUSSION: Self-help using BA for older people at risk of depression is a feasible and scalable intervention with potential short-term benefits in preventing depression.

MGnify: the microbiome analysis resource in 2020.

MGnify (http://www.ebi.ac.uk/metagenomics) provides a free to use platform for the assembly, analysis and archiving of microbiome data derived from sequencing microbial populations that are present in particular environments. Over the past 2 years, MGnify (formerly EBI Metagenomics) has more than doubled the number of publicly available analysed datasets held within the resource. Recently, an updated approach to data analysis has been unveiled (version 5.0), replacing the previous single pipeline with multiple analysis pipelines that are tailored according to the input data, and that are formally described using the Common Workflow Language, enabling greater provenance, reusability, and reproducibility. MGnify's new analysis pipelines offer additional approaches for taxonomic assertions based on ribosomal internal transcribed spacer regions (ITS1/2) and expanded protein functional annotations. Biochemical pathways and systems predictions have also been added for assembled contigs. MGnify's growing focus on the assembly of metagenomic data has also seen the number of datasets it has assembled and analysed increase six-fold. The non-redundant protein database constructed from the proteins encoded by these assemblies now exceeds 1 billion sequences. Meanwhile, a newly developed contig viewer provides fine-grained visualisation of the assembled contigs and their enriched annotations.

Investigating Changes in Patients' Smoking Behavior, Tobacco Dependence, and Motivation to Stop Smoking Following a "Smoke-Free" Mental Health Inpatient Stay: Results From a Longitudinal Survey in England.

INTRODUCTION: In line with national guidance, mental health Trusts in England are implementing complete smoke-free policies. We investigated inpatients' changes in smoking behavior, tobacco dependence, vaping, and motivation to stop smoking between pre-admission and post-discharge. METHODS: We surveyed acute adult mental health inpatients from 14 wards in three mental health Trusts in England in 2019. Structured face-to-face and telephone interviews with patients who smoked on or during admission were conducted during the admission period and at one week and one month after discharge. Data on smoking status; daily cigarette consumption; Heaviness of Smoking Index (HSI); Strength of Urges to Smoke (SUTS); Motivation to Stop Smoking (MTSS) and vaping were collected and analyzed using regression and probit models. RESULTS: Inpatient smoking prevalence was 51.9%, and a total of 152 of all 555 eligible smokers (27%) were recruited. Attrition was high: 49.3% at the first and 50.7% at the second follow-up interview. Changes in self-reported smoking status, motivation to quit, and vaping did not change significantly over the study period. Cigarette consumption (p < 0.001) and Heaviness of Smoking Index (p < 0.001) modestly reduced. The frequency and strength of urges to smoke (p = 0.011 and 0.012, respectively) decreased modestly after discharge but were scored as high by 57% and 60% of participants during admission respectively. Just over half (56%) reported being offered smoking cessation support on admission. CONCLUSIONS: This study identified very modest changes in smoking-related outcomes during and after admission and indicates major challenges to smoke-free policy implementation, including limited support for patients who smoke. IMPLICATIONS: Despite mental health Trusts in England had developed and implemented smoke-free policies to meet national guidelines, adherence to these policies and provision of effective smoking cessation and temporary abstinence support for inpatients admitted to acute adult mental health wards appear to be limited. Patients who smoke on admission are likely to continue to do so during admission and after discharge, and only a very modest change in smoking behaviors appears to take place. Important opportunities to promote smoking cessation in this population are missed. Barriers to effective support need to be identified and addressed.

InterPro in 2019: improving coverage, classification and access to protein sequence annotations.

The InterPro database (http://www.ebi.ac.uk/interpro/) classifies protein sequences into families and predicts the presence of functionally important domains and sites. Here, we report recent developments with InterPro (version 70.0) and its associated software, including an 18% growth in the size of the database in terms on new InterPro entries, updates to content, the inclusion of an additional entry type, refined modelling of discontinuous domains, and the development of a new programmatic interface and website. These developments extend and enrich the information provided by InterPro, and provide greater flexibility in terms of data access. We also show that InterPro's sequence coverage has kept pace with the growth of UniProtKB, and discuss how our evaluation of residue coverage may help guide future curation activities.

EBI Metagenomics in 2017: enriching the analysis of microbial communities, from sequence reads to assemblies.

EBI metagenomics (http://www.ebi.ac.uk/metagenomics) provides a free to use platform for the analysis and archiving of sequence data derived from the microbial populations found in a particular environment. Over the past two years, EBI metagenomics has increased the number of datasets analysed 10-fold. In addition to increased throughput, the underlying analysis pipeline has been overhauled to include both new or updated tools and reference databases. Of particular note is a new workflow for taxonomic assignments that has been extended to include assignments based on both the large and small subunit RNA marker genes and to encompass all cellular micro-organisms. We also describe the addition of metagenomic assembly as a new analysis service. Our pilot studies have produced over 2400 assemblies from datasets in the public domain. From these assemblies, we have produced a searchable, non-redundant protein database of over 50 million sequences. To provide improved access to the data stored within the resource, we have developed a programmatic interface that provides access to the analysis results and associated sample metadata. Finally, we have integrated the results of a series of statistical analyses that provide estimations of diversity and sample comparisons.

Baseline testing in cluster randomised controlled trials: should this be done?

BACKGROUND: Comparisons of baseline covariates in randomised controlled trials whilst often undertaken is regarded by many as an exercise in futility. Because of randomisation the null hypothesis is true for baseline comparisons and therefore any differences will occur by chance. However, this is only the case if allocations are not known in advance of recruitment. If this occurs then selection bias at randomisation may be present and it is possible that the statistical testing of covariates may unveil selection bias. In this paper we show that this is particularly the case for cluster randomised trials when post-randomised recruitment often occurs and can lead to selection bias. MAIN TEXT: We take a recently published cluster randomised trial that has suffered from selection bias due to differential recruitment and calculate baseline p values. We show that statistically significant imbalances of p < 0.0001 occurred in 5 of the 10 covariates. In comparison for an individually randomised trial that had no evidence of selection bias only 1 p value of p < 0.05 out of 20 tests was observed. Had baseline p values for the cluster trial been presented to journal editors, reviewers and readers then the results of the trial might have been treated with more caution. CONCLUSION: We argue that the blanket ban of baseline testing as advocated by some may reduce the chance of identifying deficient cluster randomised trials and this opposition should be reconsidered for cluster trials.

The impact of automated screening with Edmonton Symptom Assessment System (ESAS) on health-related quality of life, supportive care needs, and patient satisfaction with care in 268 ambulatory cancer patients.

PURPOSE: We aimed to assess the impact of implementing Edmonton Symptom Assessment System (ESAS) screening on health-related quality of life (HRQoL) and patient satisfaction with care (PSC) in ambulatory oncology patients. ESAS is now a standard of care in Ontario cancer centers, with the goal of improving symptom management in cancer patients, yet few studies examine impact of ESAS on patient outcomes. METHODS: We compared ambulatory oncology patients who were not screened prior to ESAS site implementation (2011-2012), to a similar group who were screened using ESAS after site implementation (2012-2013), to examine between-group differences in patient HRQoL, PSC outcomes, and supportive care needs (Supportive Care Service Survey). Both no-ESAS (n = 160) and ESAS (n = 108) groups completed these measures: the latter completing them, along with ESAS, at baseline and 2 weeks later. RESULTS: After assessing the impact of implementing ESAS, by matching for potentially confounding variables and conducting univariate analyses, no significant between-group differences were found in HRQoL or PSC. There was significant improvement in symptoms of nausea/vomiting and constipation, after 2 weeks. Lower symptom burden with decreased ESAS scores was significantly correlated with increased HRQoL. There were no between-group differences in knowledge of/access to supportive care. CONCLUSIONS: Significant correlation between change in ESAS and HRQoL implies ESAS could usefully inform healthcare providers about need to respond to changes in symptom and functioning between visits. This study showed no impact of early-ESAS screening on HRQoL or PSC. Further research should explore how to better utilize ESAS screening, to improve communication, symptom management, and HRQoL.

Normative values for the distress thermometer (DT) and the emotion thermometers (ET), derived from a German general population sample.

PURPOSE: The distress thermometer (DT) and the emotion thermometers (ET) are short screening instruments for use in oncological practice. The aim of this study was to provide normative values and to analyze the correlational structure of the ET. METHODS: A representative sample of the adult German general population (N = 2437) completed the ET, the PHQ-4, the FACIT-fatigue scale, and the demoralization scale. RESULTS: The percentages of people above the cutoff (≥ 4) and the mean scores of the five ET scales were as follows: distress: 39.0%, M = 3.15 ± 2.62, anxiety: 12.3%, M = 1.36 ± 1.93, depression: 16.1%, M = 1.65 ± 2.11, anger: 24.5%, M = 2.33 ± 2.16, and need for help: 10.7%, M = 1.18 ± 1.90. Women reported significantly higher levels of burden than men, with effect sizes between 0.07 (anger) and 0.36 (anxiety). All ET dimensions were interrelated (r between 0.44 and 0.69) and significantly correlated with the other scales (r between 0.36 and 0.68). CONCLUSIONS: The normative scores can help qualify assessments of groups of patients. The new four dimensions of the ET provide relevant additional information that is not already covered by the DT.

InterPro in 2017-beyond protein family and domain annotations.

InterPro (http://www.ebi.ac.uk/interpro/) is a freely available database used to classify protein sequences into families and to predict the presence of important domains and sites. InterProScan is the underlying software that allows both protein and nucleic acid sequences to be searched against InterPro's predictive models, which are provided by its member databases. Here, we report recent developments with InterPro and its associated software, including the addition of two new databases (SFLD and CDD), and the functionality to include residue-level annotation and prediction of intrinsic disorder. These developments enrich the annotations provided by InterPro, increase the overall number of residues annotated and allow more specific functional inferences.

Screening for emotional disorders in patients with cancer using the Brief Symptom Inventory (BSI) and the BSI-18 versus a standardized psychiatric interview (the World Health Organization Composite International Diagnostic Interview).

BACKGROUND: Given the adverse consequences of psychiatric and psychosocial morbidity on the quality of life for patients with cancer, prompt detection of psychological symptoms is mandatory. The authors examined the properties and accuracy of the Brief Symptom Inventory (the 53-item version [BSI] and the 18-item version [BSI-18]) for the detection of psychiatric morbidity compared with the World Health Organization Composite International Diagnostic Interview (CIDI) for International Classification of Diseases-10th Revision psychiatric diagnoses. METHODS: A convenience sample of 498 patients with newly diagnosed cancer who were recruited in cancer outpatient services participated in the CIDI interview and in BSI and BSI-18 assessments. RESULTS: The prevalence of psychiatric morbidity was 39.75%. When participants were classified as cases using the BSI standard case rule, agreement with the CIDI was potentially acceptable (sensitivity, 72.7%; specificity, 88.7%). In contrast, the accuracy of the BSI-18 in identifying cases was poor according to the standard case rule, with very low sensitivity (29.3%) (misclassification rate, 28.7%). By using a first alternative case-rule system (a BSI-18 global severity index [GSI] T-score ≥57), sensitivity marginally improved (45%), whereas a second alternative case-rule system (a GSI T-score ≥50) significantly increased sensitivity (77.3%). In receiver operating characteristic curve analysis, a further cutoff GSI T-score ≥48 exhibited good discrimination levels (sensitivity, 82.3%; specificity, 72.4%). There were some differences in GSI cutoff T-scores according to the International Classification of Diseases-10th Revision diagnosis and sex. CONCLUSIONS: The BSI appeared to have acceptable diagnostic accuracy compared with a standardized psychiatric interview. For the BSI-18, it is mandatory to use alternative case-rule systems, to identify patients with psychiatric morbidity. Cancer 2018;124:2415-26. © 2018 American Cancer Society.

PROMIS depression measures perform similarly to legacy measures relative to a structured diagnostic interview for depression in cancer patients.

PURPOSE: To assess the convergent validity of the Patient-Reported Outcomes Measurement Information System (PROMIS) depression measures relative to legacy measures and criterion validity against a structured diagnostic interview for depression in an oncology sample. METHODS: 132 oncology/haematology outpatients completed the PROMIS Depression Computer Adaptive Test (PROMIS-D-CAT) and PROMIS Depression Short Form (PROMIS-D-SF) along with seven legacy measures: Beck Depression Inventory (BDI); Centre for Epidemiological Studies Depression (CES-D); Depression, Anxiety and Stress Scale; Hospital Anxiety and Depression Scale; Patient Health Questionnaire; Distress Thermometer and PSYCH-6. Correlations, area under the curve (AUC) and diagnostic accuracy statistics were calculated with Structured Clinical Interview as the gold standard. RESULTS: Both PROMIS measures correlated with all legacy measures at p < .001 (ρ = 0.589-0.810) and all AUCs (> 0.800) were comparable. At the cut-off points for mild depression of 53, the PROMIS measures had sensitivity (0.83 for PROMIS-D-CAT and 0.80 for PROMIS-D-SF) similar to or better than 6/7 legacy measures with high negative predictive value (> 90%). At cut-off points of 60 for moderate depression, PROMIS measures had specificity > 90%, similar to or better than all legacy measures and positive predictive value ≥ 0.50 (similar to 5/7 legacy measures). CONCLUSIONS: The convergent and criterion validity of the PROMIS depression measures in cancer populations was confirmed, although the optimal cut-off points are not established. PROMIS measures were briefer than BDI-II and CES-D but do not offer any advance in terms of diagnostic accuracy, reduced response burden or cost over other legacy measures of depression in oncology patients.

HPMCD: the database of human microbial communities from metagenomic datasets and microbial reference genomes.

The Human Pan-Microbe Communities (HPMC) database (http://www.hpmcd.org/) provides a manually curated, searchable, metagenomic resource to facilitate investigation of human gastrointestinal microbiota. Over the past decade, the application of metagenome sequencing to elucidate the microbial composition and functional capacity present in the human microbiome has revolutionized many concepts in our basic biology. When sufficient high quality reference genomes are available, whole genome metagenomic sequencing can provide direct biological insights and high-resolution classification. The HPMC database provides species level, standardized phylogenetic classification of over 1800 human gastrointestinal metagenomic samples. This is achieved by combining a manually curated list of bacterial genomes from human faecal samples with over 21000 additional reference genomes representing bacteria, viruses, archaea and fungi with manually curated species classification and enhanced sample metadata annotation. A user-friendly, web-based interface provides the ability to search for (i) microbial groups associated with health or disease state, (ii) health or disease states and community structure associated with a microbial group, (iii) the enrichment of a microbial gene or sequence and (iv) enrichment of a functional annotation. The HPMC database enables detailed analysis of human microbial communities and supports research from basic microbiology and immunology to therapeutic development in human health and disease.

EBI metagenomics in 2016--an expanding and evolving resource for the analysis and archiving of metagenomic data.

EBI metagenomics (https://www.ebi.ac.uk/metagenomics/) is a freely available hub for the analysis and archiving of metagenomic and metatranscriptomic data. Over the last 2 years, the resource has undergone rapid growth, with an increase of over five-fold in the number of processed samples and consequently represents one of the largest resources of analysed shotgun metagenomes. Here, we report the status of the resource in 2016 and give an overview of new developments. In particular, we describe updates to data content, a complete overhaul of the analysis pipeline, streamlining of data presentation via the website and the development of a new web based tool to compare functional analyses of sequence runs within a study. We also highlight two of the higher profile projects that have been analysed using the resource in the last year: the oceanographic projects Ocean Sampling Day and Tara Oceans.

The Pfam protein families database: towards a more sustainable future.

In the last two years the Pfam database (http://pfam.xfam.org) has undergone a substantial reorganisation to reduce the effort involved in making a release, thereby permitting more frequent releases. Arguably the most significant of these changes is that Pfam is now primarily based on the UniProtKB reference proteomes, with the counts of matched sequences and species reported on the website restricted to this smaller set. Building families on reference proteomes sequences brings greater stability, which decreases the amount of manual curation required to maintain them. It also reduces the number of sequences displayed on the website, whilst still providing access to many important model organisms. Matches to the full UniProtKB database are, however, still available and Pfam annotations for individual UniProtKB sequences can still be retrieved. Some Pfam entries (1.6%) which have no matches to reference proteomes remain; we are working with UniProt to see if sequences from them can be incorporated into reference proteomes. Pfam-B, the automatically-generated supplement to Pfam, has been removed. The current release (Pfam 29.0) includes 16 295 entries and 559 clans. The facility to view the relationship between families within a clan has been improved by the introduction of a new tool.

The InterPro protein families database: the classification resource after 15 years.

The InterPro database (http://www.ebi.ac.uk/interpro/) is a freely available resource that can be used to classify sequences into protein families and to predict the presence of important domains and sites. Central to the InterPro database are predictive models, known as signatures, from a range of different protein family databases that have different biological focuses and use different methodological approaches to classify protein families and domains. InterPro integrates these signatures, capitalizing on the respective strengths of the individual databases, to produce a powerful protein classification resource. Here, we report on the status of InterPro as it enters its 15th year of operation, and give an overview of new developments with the database and its associated Web interfaces and software. In particular, the new domain architecture search tool is described and the process of mapping of Gene Ontology terms to InterPro is outlined. We also discuss the challenges faced by the resource given the explosive growth in sequence data in recent years. InterPro (version 48.0) contains 36,766 member database signatures integrated into 26,238 InterPro entries, an increase of over 3993 entries (5081 signatures), since 2012.

Physical multimorbidity and psychosis: comprehensive cross sectional analysis including 242,952 people across 48 low- and middle-income countries.

BACKGROUND: In people with psychosis, physical comorbidities, including cardiovascular and metabolic diseases, are highly prevalent and leading contributors to the premature mortality encountered. However, little is known about physical health multimorbidity in this population or in people with subclinical psychosis and in low- and middle-income countries (LMICs). This study explores physical health multimorbidity patterns among people with psychosis or subclinical psychosis. METHODS: Overall, data from 242,952 individuals from 48 LMICs, recruited via the World Health Survey, were included in this cross-sectional study. Participants were subdivided into those (1) with a lifetime diagnosis of psychosis ("psychosis"); (2) with more than one psychotic symptom in the past 12 months, but no lifetime diagnosis of psychosis ("subclinical psychosis"); and (3) without psychotic symptoms in the past 12 months or a lifetime diagnosis of psychosis ("controls"). Nine operationalized somatic disorders were examined: arthritis, angina pectoris, asthma, diabetes, chronic back pain, visual impairment, hearing problems, edentulism, and tuberculosis. The association between psychosis and multimorbidity was assessed by multivariable logistic regression analysis. RESULTS: The prevalence of multimorbidity (i.e., two or more physical health conditions) was: controls = 11.4% (95% CI, 11.0-11.8%); subclinical psychosis = 21.8% (95% CI, 20.6-23.0%), and psychosis = 36.0% (95% CI, 32.1-40.2%) (P < 0.0001). After adjustment for age, sex, education, country-wise wealth, and country, subclinical psychosis and psychosis were associated with 2.20 (95% CI, 2.02-2.39) and 4.05 (95% CI, 3.25-5.04) times higher odds for multimorbidity. Moreover, multimorbidity was increased in subclinical and established psychosis in all age ranges (18-44, 45-64, ≥ 65 years). However, multimorbidity was most evident in younger age groups, with people aged 18-44 years with psychosis at greatest odds of physical health multimorbidity (OR = 4.68; 95% CI, 3.46-6.32). CONCLUSIONS: This large multinational study demonstrates that physical health multimorbidity is increased across the psychosis-spectrum. Most notably, the association between multimorbidity and psychosis was stronger among younger adults, thus adding further impetus to the calls for the early intervention efforts to prevent the burden of physical health comorbidity at later stages. Urgent public health interventions are necessary not only for those with a psychosis diagnosis, but also for subclinical psychosis to address this considerable public health problem.

A comparison study of cognitive deficits in radiologically and clinically isolated syndromes.

UNLABELLED: Up until now, no information has existed regarding a comparison of the pattern and frequency of cognitive deficits between radiologically isolated syndrome (RIS) and clinically isolated syndrome (CIS) patients. Within this objective, Rao's Brief Repeatable Battery and Stroop test were administered to 28 RIS patients, 25 CIS patients, and 22 healthy controls. CONCLUSIONS: The prevalence of cognitive deficits in RIS was similar to that of CIS. Cognitive deficits seem to be present in RIS patients regardless of the presence of risk factors for a future symptomatic demyelinating event.