Functional and evolutionary significance of unknown genes from uncultivated taxa.

Many of the Earth's microbes remain uncultured and understudied, limiting our understanding of the functional and evolutionary aspects of their genetic material, which remain largely overlooked in most metagenomic studies1. Here we analysed 149,842 environmental genomes from multiple habitats2-6 and compiled a curated catalogue of 404,085 functionally and evolutionarily significant novel (FESNov) gene families exclusive to uncultivated prokaryotic taxa. All FESNov families span multiple species, exhibit strong signals of purifying selection and qualify as new orthologous groups, thus nearly tripling the number of bacterial and archaeal gene families described to date. The FESNov catalogue is enriched in clade-specific traits, including 1,034 novel families that can distinguish entire uncultivated phyla, classes and orders, probably representing synapomorphies that facilitated their evolutionary divergence. Using genomic context analysis and structural alignments we predicted functional associations for 32.4% of FESNov families, including 4,349 high-confidence associations with important biological processes. These predictions provide a valuable hypothesis-driven framework that we used for experimental validatation of a new gene family involved in cell motility and a novel set of antimicrobial peptides. We also demonstrate that the relative abundance profiles of novel families can discriminate between environments and clinical conditions, leading to the discovery of potentially new biomarkers associated with colorectal cancer. We expect this work to enhance future metagenomics studies and expand our knowledge of the genetic repertory of uncultivated organisms.

eggNOG 6.0: enabling comparative genomics across 12 535 organisms.

The eggNOG (evolutionary gene genealogy Non-supervised Orthologous Groups) database is a bioinformatics resource providing orthology data and comprehensive functional information for organisms from all domains of life. Here, we present a major update of the database and website (version 6.0), which increases the number of covered organisms to 12 535 reference species, expands functional annotations, and implements new functionality. In total, eggNOG 6.0 provides a hierarchy of over 17M orthologous groups (OGs) computed at 1601 taxonomic levels, spanning 10 756 bacterial, 457 archaeal and 1322 eukaryotic organisms. OGs have been thoroughly annotated using recent knowledge from functional databases, including KEGG, Gene Ontology, UniProtKB, BiGG, CAZy, CARD, PFAM and SMART. eggNOG also offers phylogenetic trees for all OGs, maximising utility and versatility for end users while allowing researchers to investigate the evolutionary history of speciation and duplication events as well as the phylogenetic distribution of functional terms within each OG. Furthermore, the eggNOG 6.0 website contains new functionality to mine orthology and functional data with ease, including the possibility of generating phylogenetic profiles for multiple OGs across species or identifying single-copy OGs at custom taxonomic levels. eggNOG 6.0 is available at http://eggnog6.embl.de.

PhyloCloud: an online platform for making sense of phylogenomic data.

Phylogenomics data have grown exponentially over the last decades. It is currently common for genome-wide projects to generate hundreds or even thousands of phylogenetic trees and multiple sequence alignments, which may also be very large in size. However, the analysis and interpretation of such data still depends on custom bioinformatic and visualisation workflows that are largely unattainable for non-expert users. Here, we present PhyloCloud, an online platform aimed at hosting, indexing and exploring large phylogenetic tree collections, providing also seamless access to common analyses and operations, such as node annotation, searching, topology editing, automatic tree rooting, orthology detection and more. In addition, PhyloCloud provides quick access to tools that allow users to build their own phylogenies using fast predefined workflows, graphically compare tree topologies, or query taxonomic databases such as NBCI or GTDB. Finally, PhyloCloud offers a novel tree visualisation system based on ETE Toolkit v4.0, which can be used to explore very large trees and enhance them with custom annotations and multiple sequence alignments. The platform allows for sharing tree collections and specific tree views via private links, or make them fully public, serving also as a repository of phylogenomic data. PhyloCloud is available at https://phylocloud.cgmlab.org.

Impact of house dust mite-driven asthma on children's school performance and activity.

Evidence regarding asthma's impact on children's daily lives is limited. This prospective and cross-sectional, observational, multicenter study assessed school/work and activity impairment in children and adolescents with allergic asthma and their caregivers and allergen immunotherapy (AIT) effects. Included patients were schooled children and adolescents (5 to 17 years) with allergic asthma due to house dust mites (HDM). Impairment of school/work (i.e., absenteeism and presenteeism) and activity was measured in patients and their caregivers using the Work Productivity Impairment Questionnaire plus Classroom Impairment Questions: Allergy Specific (WPAI + CIQ:AS). HDM allergic patients with school impairment received subcutaneous AIT with a MicroCrystalline Tyrosine-associated allergoid. WPAI + CIQ:AS and effectiveness variables were compared between baseline and 1-year post-AIT. Of the 113 patients included, 59 (52.2%) and 51 (45.1%) showed school and activity impairment, respectively, missing a mean (SD) of 37.6 (24.4) % and 42.6 (25.6) % of school and activity time, respectively. Twenty-six (23%) caregivers reported activity impairment and, of the 79 (69.9%) employed, 30 (38%) reported work impairment. Of the 65 patients with school/activities impairment, 41 (63.1%) received AIT, of which 21 (51.2%) completed 1 year of treatment. Effectiveness variables and WPAI + CIQ:AS significantly improved: Mean (SD) school impairment decreased from 39.7 (26.7) to 2.1 (7.1) % (p < 0.001) and activity impairment from 46.2 (34.6) to 1.4 (3.6) % (p < 0.001). CONCLUSION: Allergic asthma due to HDMs results in school/work and activity impairment in children and adolescents and their caregivers. One year of AIT provided clinical benefits and reduced school and activity impairment. WHAT IS KNOWN: • Allergic asthma impairs children's school performance and daily activities. • Allergen immunotherapy modifies allergic disease course and ameliorates its symptoms. WHAT IS NEW: • Asthma symptoms due to allergy to house dust mites impair children's school attendance and productivity and daily activity and their caregivers' work performance and daily lives. • Allergen immunotherapy with a house dust mite MicroCrystalline Tyrosine (MCT)-associated allergoid seems to provide clinical benefits, associated with decreased school and activity impairment, supporting it as an effective treatment option.

Profiling cellular diversity in sponges informs animal cell type and nervous system evolution.

The evolutionary origin of metazoan cell types such as neurons and muscles is not known. Using whole-body single-cell RNA sequencing in a sponge, an animal without nervous system and musculature, we identified 18 distinct cell types. These include nitric oxide­sensitive contractile pinacocytes, amoeboid phagocytes, and secretory neuroid cells that reside in close contact with digestive choanocytes that express scaffolding and receptor proteins. Visualizing neuroid cells by correlative x-ray and electron microscopy revealed secretory vesicles and cellular projections enwrapping choanocyte microvilli and cilia. Our data show a communication system that is organized around sponge digestive chambers, using conserved modules that became incorporated into the pre- and postsynapse in the nervous systems of other animals.

eggNOG-mapper v2: Functional Annotation, Orthology Assignments, and Domain Prediction at the Metagenomic Scale.

Even though automated functional annotation of genes represents a fundamental step in most genomic and metagenomic workflows, it remains challenging at large scales. Here, we describe a major upgrade to eggNOG-mapper, a tool for functional annotation based on precomputed orthology assignments, now optimized for vast (meta)genomic data sets. Improvements in version 2 include a full update of both the genomes and functional databases to those from eggNOG v5, as well as several efficiency enhancements and new features. Most notably, eggNOG-mapper v2 now allows for: 1) de novo gene prediction from raw contigs, 2) built-in pairwise orthology prediction, 3) fast protein domain discovery, and 4) automated GFF decoration. eggNOG-mapper v2 is available as a standalone tool or as an online service at http://eggnog-mapper.embl.de.

The Effect of Nutritional Interventions on Long-Term Patient Survival in Advanced Chronic Kidney Disease.

Patients with end-stage kidney disease (ESKD) are at high risk of malnutrition and subsequent related mortality when starting dialysis. However, there have been few clinical studies on the effect of nutritional interventions on long-term patient survival. A 2-year longitudinal study was conducted from January 2012 to December 2016. A total of 186 patients with non-dialysis ESKD started the nutritional education program (NEP), and 169 completed it. A total of 128 patients participated in a NEP over 6 months (personalized diet, education and oral supplementation, if needed). The control group (n = 45) underwent no specific nutritional intervention. The hospitalization rate was significantly lower for the patients with NEP (13.7%) compared with the control patients (26.7%) (p = 0.004). The mortality odds ratio for the patients who did not receive NEP was 2.883 (95% CI 0.993-8.3365, p = 0.051). The multivariate analysis showed an independent association between mortality and age (OR, 1.103; 95% CI 1.041-1.169; p = 0.001) and between mortality and the female sex (OR, 3.332; 95% CI 1.054-10.535; p = 0.040) but not between mortality and those with NEP (p = 0.051). Individualized nutrition education has long-term positive effects on nutritional status, reduces hospital admissions and increases survival among patients with advanced CKD who are starting dialysis programs.

Clinical outcomes with a new design in multifocal intraocular lens: a pilot study.

PURPOSE: To evaluate the clinical and visual outcomes, quality of near vision and the influence of photic phenomena in patients bilaterally implanted with a new Precizon Presbyopic multifocal intraocular lens (IOL). METHODS: In this prospective consecutive case series, 20 eyes of 10 patients were included (mean age 63.80 ± 12.55 years). Uncorrected and corrected visual acuity (far, intermediate and near), subjective refraction, binocular defocus curve, contrast sensitivity (CSV-1000) and quality of vision and satisfaction questionnaires were measured. The follow-up was 12 months after surgery. RESULTS: At 12 months after surgery, uncorrected distance visual acuity (UDVA) improved with surgery (p = 0.001) with a value of 0.08 ± 0.08 logMAR. Uncorrected near visual acuity (UNVA) was 0.22 ± 0.12 logMAR and distance corrected near visual acuity (DCNVA) was 0.16 ± 0.13 logMAR. Intermediate distance visual acuity (UIVA) was 0.22 ± 0.10 logMAR. Contrast sensitivity outcomes were similar to normal population in photopic conditions and slightly reduced in mesopic conditions of lighting. Defocus curve showed that this multifocal IOL was able to provide a visual acuity (VA) equal or better to 0.16 logMAR between defocus levels of + 1.00 to - 2.50 D. Good patient satisfaction was obtained in quality of vision and satisfaction questionnaires outcomes. CONCLUSIONS: The Precizon Presbyopic NVA IOL (OPHTEC BV) provides good visual outcomes. This multifocal IOL provides a high percentage of spectacle independence due to good VA at far, intermediate and near distances and satisfactory contrast sensitivity. High patient satisfaction was observed in quality of vision and satisfaction questionnaires with a low percentage of patients manifesting photic phenomena.

Coronavirus Disease 2019 in Pregnancy: A Clinical Management Protocol and Considerations for Practice.

The coronavirus disease 2019 (COVID-19) pandemic has represented a major impact to health systems and societies worldwide. The generation of knowledge about the disease has occurred almost as fast as its global expansion. The mother and fetus do not seem to be at particularly high risk. Nevertheless, obstetrics and maternal-fetal medicine practice have suffered profound changes to adapt to the pandemic. In addition, there are aspects specific to COVID-19 and gestation that should be known by specialists in order to correctly diagnose the disease, classify the severity, distinguish specific signs of COVID-19 from those of obstetric complications, and take the most appropriate management decisions. In this review we present in a highly concise manner an evidence-based protocol for the management of COVID-19 in pregnancy. We briefly contemplate all relevant aspects that we believe a specialist in obstetrics and maternal medicine should know, ranging from basic concepts about the disease and protection measures in the obstetric setting to more specific aspects related to maternal-fetal management and childbirth.

The Quest for Orthologs benchmark service and consensus calls in 2020.

The identification of orthologs-genes in different species which descended from the same gene in their last common ancestor-is a prerequisite for many analyses in comparative genomics and molecular evolution. Numerous algorithms and resources have been conceived to address this problem, but benchmarking and interpreting them is fraught with difficulties (need to compare them on a common input dataset, absence of ground truth, computational cost of calling orthologs). To address this, the Quest for Orthologs consortium maintains a reference set of proteomes and provides a web server for continuous orthology benchmarking (http://orthology.benchmarkservice.org). Furthermore, consensus ortholog calls derived from public benchmark submissions are provided on the Alliance of Genome Resources website, the joint portal of NIH-funded model organism databases.

Single-cycle rituximab-induced immunologic changes in children: Enhanced in neuroimmunologic disease?

OBJECTIVE: To investigate the immunologic impact of a single cycle of rituximab (RTX) in children and adolescents with immune-mediated disorders, we evaluated B cells and immunoglobulin levels of 20 patients with neuroimmunologic, nephrologic, dermatologic, and rheumatologic disorders treated under recommended guidelines. METHODS: Retrospective study of immunologic changes in children (aged ≤18 years) diagnosed with immune-mediated disorders in which RTX was prescribed between June 2014 and February 2019. Patients were excluded if they had prior diagnosis of malignant disease or primary immunodeficiency. Patients were clinically and immunologically followed up every 3 months. Only patients having received a single cycle of RTX and with a follow-up greater than 12 months were included in the analysis of persistent dysgammaglobulinemia. RESULTS: Twenty children were included. Median age at RTX treatment was 12.8 years (interquartile range [IQR] 6.6-15.5 years). Median follow-up was 12.6 months (IQR 10.2-24 months). Of the 14 patients eligible for persistent dysgammaglobulinemia analysis (3 had received RTX retreatment, 2 had <12 months post-RTX follow-up, and in 1 data for this time point was missing), 2/14 (14%) remained with complete B-cell depletion, and 5/14 (36%) had dysgammaglobulinemia. Patients with dysgammaglobulinemia were younger (7.8 vs 15.6 years, p = 0.072), had more underlying neuroimmunologic diseases (5/5 vs 0/9, p < 0.001), and had received more frequently concentrated doses of RTX (3/5 vs 1/9, p = 0.05) than patients without dysgammaglobulinemia. Kinetics of immunoglobulins in the 20 patients revealed a decrease as early as 3 months after RTX in patients with neuroimmunologic disorders. CONCLUSION: In our cohort, single-cycle RTX-induced dysgammaglobulinemia was enhanced in patients with neuroimmunologic diseases. Further studies are needed to confirm this observation.

Factors predicting successful customized excimer laser treatment in irregular corneas.

PURPOSE: To identify factors associated with a successful wavefront-guided customized treatment (WG-CT) with an excimer laser in highly aberrated corneas. SETTING: VISSUM Alicante Spain. DESIGN: Retrospective consecutive noncomparative case series. METHODS: Treatment was performed with the WG-CT Amaris excimer laser using the ORK-CAM software for the calculation of the ablation profile. Eyes of patients with significantly aberrated corneas, including postrefractive and keratoplasty procedures or high irregular astigmatism with significant higher-order aberrations (HOAs) that had WG-CT were included. Refractive outcomes, HOAs, and visual outcomes were recorded. Statistical analysis was performed to identify factors associated with technical (based on HOAs) or refractive outcome success. RESULTS: The study included 55 treatments of 51 eyes (35 patients). The postoperative uncorrected distance visual acuity was 0.2 logarithm of the minimum angle of resolution or better in 72% of the eyes, and the postoperative residual manifest refraction spherical equivalent was ±0.50 diopter in 56% of the eyes, whereas 11% of the eyes lost 1 line or more in corrected distance visual acuity. Successful reduction in the total root mean square (RMS) of HOAs occurred in 36 eyes (65%), and these eyes had a significantly higher preoperative RMS of HOAs (1.45 ± 0.93 µ vs 0.91 ± 0.34 µ, P = .003) and preoperative coma-like aberrations (1.09 ± 0.83 µ vs 0.55 ± 0.28 µ, P = .001). In multivariate analysis, posthyperopic treatment eyes were less likely to achieve refractive outcome success (odds ratio = 0.09, P = .02). CONCLUSIONS: WG-CT in highly aberrated corneas had a limited refractive predictability. Eyes with preoperative coma-like aberrations are more likely to benefit from a reduction in HOAs. Posthyperopic treatment is associated with a higher rate of refractive surprises.

Relationship Between Atopic Dermatitis and Food Allergy.

Consistent evidence has been found on the relationship between food allergy (FA) and atopic dermatitis (AD) in some children. Food sensitization can be often found in these patients. Allergy should be confirmed, though, with a food challenge test (FC) before advising a restrictive diet which could be harmful for the patient. Younger children with AD frequently show sensitization to egg, milk or peanut, while older ones and adults are more often sensitized to environmental allergens such as house dust mites, moulds, animal dander or pollens. It is well known that a barrier disturbance plays a main role in the development of sensitization and allergy. Therefore, due to the early appearance of AD, preventive newborn skincare with emollients and early introduction of food appear to be very important to determine food tolerance.

proGenomes2: an improved database for accurate and consistent habitat, taxonomic and functional annotations of prokaryotic genomes.

Microbiology depends on the availability of annotated microbial genomes for many applications. Comparative genomics approaches have been a major advance, but consistent and accurate annotations of genomes can be hard to obtain. In addition, newer concepts such as the pan-genome concept are still being implemented to help answer biological questions. Hence, we present proGenomes2, which provides 87 920 high-quality genomes in a user-friendly and interactive manner. Genome sequences and annotations can be retrieved individually or by taxonomic clade. Every genome in the database has been assigned to a species cluster and most genomes could be accurately assigned to one or multiple habitats. In addition, general functional annotations and specific annotations of antibiotic resistance genes and single nucleotide variants are provided. In short, proGenomes2 provides threefold more genomes, enhanced habitat annotations, updated taxonomic and functional annotation and improved linkage to the NCBI BioSample database. The database is available at http://progenomes.embl.de/.

Multimorbidities of Pediatric Allergic Rhinitis.

PURPOSE OF REVIEW: Most children and adolescents with allergic rhinitis (AR) present extra-nasal multimorbid conditions, including conjunctivitis, asthma, atopic dermatitis, rhinosinusitis, or seromucous otitis. Additionally, they may present nasal obstructive disorders, such as septal deformity, turbinate enlargement, and adenoidal hyperplasia, which worsen nasal symptoms, especially nasal obstruction. This is a narrative review on the current state of the concomitant presence of AR and one or more multimorbidities. RECENT FINDINGS: The presence of AR and one or more accompanying multimorbidities is associated to a higher severity and duration of the disease, a negative impact on quality of life, with worse control and lack of improvement with medical treatment. Therefore, AR needs to be managed with a multidisciplinary collaborative approach. Pediatric AR needs to be considered in the context of a systemic disease, which requires a coordinated therapeutic strategy.