The EMBL-EBI Job Dispatcher sequence analysis tools framework in 2024.

The EMBL-EBI Job Dispatcher sequence analysis tools framework (https://www.ebi.ac.uk/jdispatcher) enables the scientific community to perform a diverse range of sequence analyses using popular bioinformatics applications. Free access to the tools and required sequence datasets is provided through user-friendly web applications, as well as via RESTful and SOAP-based APIs. These are integrated into popular EMBL-EBI resources such as UniProt, InterPro, ENA and Ensembl Genomes. This paper overviews recent improvements to Job Dispatcher, including its brand new website and documentation, enhanced visualisations, improved job management, and a rising trend of user reliance on the service from low- and middle-income regions.

Periodontitis is associated with impaired olfactory function: A clinical study.

AIM: To explore the association between periodontitis and olfactory disorders. METHODS: Clinical data were collected from 198 individuals between the ages of 18 and 60 years living in Denmark. The exposure was periodontitis, and the outcome was olfactory function (Threshold, Discrimination, Identification - TDI score), both measured clinically. Covariates included sex, age, education level, income, usage of nasal spray, tongue coating, halitosis, xerostomia, smoking, and history of COVID-19. Structural equation modeling was used to estimate the association between periodontitis and olfactory function. Periodontitis was defined using the AAP/EFP classification and dichotomized into "no" (healthy subjects) and "yes" (Stages I, II, and III). Olfactory function was treated as a one-factor latent variable, including the different olfactory scores. In addition, extra models were performed considering each olfactory component as a separate outcome and the TDI Global Score. RESULTS: The results showed that periodontitis was associated with a lower olfactory function [standardized coefficient (SC) -0.264, 95% CI -0.401, -0.118]. Additionally, periodontitis was also associated with a lower olfactory Threshold (odorant concentration required for detection) (SC -0.207, 95% CI -0.325, -0.089), Discrimination (ability to discriminate between odorants) (SC -0.149, 95% CI -0.270, -0.027), Identification (ability to identify odorants) scores (SC -0.161, 95% CI -0.277, -0.045), and TDI Global Score (SC -0.234, 95% CI -0.370, -0.099). CONCLUSIONS: This study suggests that periodontitis is associated with olfactory impairment.

Search and sequence analysis tools services from EMBL-EBI in 2022.

The EMBL-EBI search and sequence analysis tools frameworks provide integrated access to EMBL-EBI's data resources and core bioinformatics analytical tools. EBI Search (https://www.ebi.ac.uk/ebisearch) provides a full-text search engine across nearly 5 billion entries, while the Job Dispatcher tools framework (https://www.ebi.ac.uk/services) enables the scientific community to perform a diverse range of sequence analysis using popular bioinformatics applications. Both allow users to interact through user-friendly web applications, as well as via RESTful and SOAP-based APIs. Here, we describe recent improvements to these services and updates made to accommodate the increasing data requirements during the COVID-19 pandemic.

The European Nucleotide Archive in 2021.

The European Nucleotide Archive (ENA, https://www.ebi.ac.uk/ena), maintained at the European Molecular Biology Laboratory's European Bioinformatics Institute (EMBL-EBI) provides freely accessible services, both for deposition of, and access to, open nucleotide sequencing data. Open scientific data are of paramount importance to the scientific community and contribute daily to the acceleration of scientific advance. Here, we outline the major updates to ENA's services and infrastructure that have been delivered over the past year.

A Systematic Review of the Effectiveness of Non-Pharmacological Therapies Used by Nurses in Children Undergoing Surgery.

OBJECTIVE: The aim of this study was to identify non-pharmacological pain relief therapies in children undergoing surgery. DESIGN AND DATA SOURCES: Using keywords extracted from Medical Subject Headings and "Descriptores en Ciencias de la Salud" we searched for articles in the Web of Science, Scopus, Cuiden, PubMed, and CINHAL databases from the last five years, and performed a reverse search. We assessed the documentary quality of the articles using various standardized instruments. RESULTS: The final review included eleven studies. In terms of cognitive-behavioral techniques, there is evidence that both music and video therapy are effective in reducing postoperative pain in children in seven studies, and therapeutic play in five studies. Other methods used less frequently but found to be effective included laughter therapy in one study and deep breathing in another. Regarding physical methods of pain relief, massage was found to be an effective non-pharmacological therapy for reducing pediatric postoperative pain in two studies and ineffective in another. CONCLUSIONS: In this study, we highlight the importance of non-pharmacological therapies in pediatric postoperative pain management. Cognitive-behavioral techniques, especially music therapy, video therapy, and therapeutic play, reduce pediatric postoperative pain. They are therefore effective therapies that nurses can use in this area. Further research into the effectiveness of storytelling is necessary, as the evidence is not entirely conclusive. More evidence is also needed on physical methods of pain relief, particularly massage.

Non-Thermal Solar Wind Electron Velocity Distribution Function.

The quiet-time solar wind electrons feature non-thermal characteristics when viewed from the perspective of their velocity distribution functions. They typically have an appearance of being composed of a denser thermal "core" population plus a tenuous energetic "halo" population. At first, such a feature was empirically fitted with the kappa velocity space distribution function, but ever since the ground-breaking work by Tsallis, the space physics community has embraced the potential implication of the kappa distribution as reflecting the non-extensive nature of the space plasma. From the viewpoint of microscopic plasma theory, the formation of the non-thermal electron velocity distribution function can be interpreted in terms of the plasma being in a state of turbulent quasi-equilibrium. Such a finding brings forth the possible existence of a profound inter-relationship between the non-extensive statistical state and the turbulent quasi-equilibrium state. The present paper further develops the idea of solar wind electrons being in the turbulent equilibrium, but, unlike the previous model, which involves the electrostatic turbulence near the plasma oscillation frequency (i.e., Langmuir turbulence), the present paper considers the impact of transverse electromagnetic turbulence, particularly, the turbulence in the whistler-mode frequency range. It is found that the coupling of spontaneously emitted thermal fluctuations and the background turbulence leads to the formation of a non-thermal electron velocity distribution function of the type observed in the solar wind during quiet times. This demonstrates that the whistler-range turbulence represents an alternative mechanism for producing the kappa-like non-thermal distribution, especially close to the Sun and in the near-Earth space environment.

SARS-CoV-2 BW lineage, a fast-growing Omicron variant from southeast Mexico bearing relevant escape mutations.

PURPOSE: The swift expansion of the BW.1 SARS-CoV-2 variant coincided with a rapid increase of COVID-19 cases occurring in Southeast Mexico in October, 2022, which marked the start of Mexico's sixth epidemiological wave. In Yucatan, up to 92% (58 of 73) of weekly sequenced genomes between epidemiological week 42 and 47 were identified as either BW.1 or its descendant, BW.1.1 in the region, during the last trimester of 2022. In the current study, a comprehensive genomic comparison was carried out to characterize the evolutionary history of the BW lineage, identifying its origins and its most important mutations. METHODS: An alignment of all the genomes of the BW lineage and its parental BA.5.6.2 variant was carried out to identify their mutations. A phylogenetic and ancestral sequence reconstruction analysis with geographical inference, as well as a longitudinal analysis of point mutations, were performed to trace back their origin and contrast them with key RBD mutations in variant BQ.1, one of the fastest-growing lineages to date. RESULTS: Our ancestral reconstruction analysis portrayed Mexico as the most probable origin of the BW.1 and BW.1.1 variants. Two synonymous substitutions, T7666C and C14599T, support their Mexican origin, whereas other two mutations are specific to BW.1: S:N460K and ORF1a:V627I. Two additional substitutions and a deletion are found in its descending subvariant, BW.1.1. Mutations found in the receptor binding domain, S:K444T, S:L452R, S:N460K, and S:F486V in BW.1 have been reported to be relevant for immune escape and are also key mutations in the BQ.1 lineage. CONCLUSIONS: BW.1 appears to have arisen in the Yucatan Peninsula in Southeast Mexico sometime around July 2022 during the fifth COVID-19 wave. Its rapid growth may be in part explained by the relevant escape mutations also found in BQ.1.

Accuracy and applicability of periodontitis risk assessment tools: A critical appraisal.

Currently, periodontal risk assessment finds application at first visit (to identify individuals at high risk of either disease incidence, if still healthy, or disease progression, if already diseased) as well as at patient monitoring after active treatment and enrolment in a supportive periodontal care program. Although the current case definition of periodontitis embeds a prognostic determination (ie, periodontitis grade) that showed a predictive value for periodontitis-related tooth loss, some limitations of periodontitis grade call for the implementation of different risk assessment tools in clinical practice. For some of these, significantly higher accuracy in predicting tooth loss during supportive periodontal care was reported compared with periodontitis grade. Validated periodontal risk assessment tools may be functional to obtain greater adherence to the suggested preventive and treatment protocols, improve oral hygiene performance, and tailor supportive periodontal care. Interestingly, periodontal risk can also be informative of the risk of peri-implantitis in patients programmed for implant placement or rehabilitated with dental implants. A critical appraisal on the rationale behind risk assessment and the balance between the advantages and limitations of exercising risk assessment in periodontology is presented.

Self-reported periodontitis association with impaired smell and taste: A multicenter survey.

OBJECTIVES: To investigate the association between self-reported periodontitis and the senses of taste and smell among employees of one Danish and two American universities. MATERIALS AND METHODS: Data were collected through a digital survey. A total of 1239 individuals from Aarhus University - Denmark, the University of Iowa, and the University of Florida - USA were included. Self-reported periodontitis was the exposure. The perceived senses of taste and smell were the outcomes and were measured through a visual analog scale (VAS). Self-perceived halitosis was the mediator. Confounders were age, sex, income, education, xerostomia, COVID-19, smoking, body mass index, and diabetes. The total effect was decomposed into direct and indirect using a counterfactual approach. RESULTS: The total effect of periodontitis on an impaired sense of taste was OR 1.56 (95% CI [1.02, 2.09]), of which 23% was mediated by halitosis (OR 1.13; 95% CI [1.03, 1.22]). Additionally, individuals with self-reported periodontitis had a 53% higher chance of having impaired smell (OR 1.53; 95% CI [1.00, 2.04]), with halitosis mediating 21% of the total effect (OR 1.11; 95% CI [1.02, 1.20]). CONCLUSION: Our findings suggest that periodontitis is associated with distorted senses of taste and smell. Additionally, this association appears to be mediated by halitosis.

The European Nucleotide Archive in 2020.

The European Nucleotide Archive (ENA; https://www.ebi.ac.uk/ena), provided by the European Molecular Biology Laboratory's European Bioinformatics Institute (EMBL-EBI), has for almost forty years continued in its mission to freely archive and present the world's public sequencing data for the benefit of the entire scientific community and for the acceleration of the global research effort. Here we highlight the major developments to ENA services and content in 2020, focussing in particular on the recently released updated ENA browser, modernisation of our release process and our data coordination collaborations with specific research communities.

The COVID-19 Data Portal: accelerating SARS-CoV-2 and COVID-19 research through rapid open access data sharing.

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic will be remembered as one of the defining events of the 21st century. The rapid global outbreak has had significant impacts on human society and is already responsible for millions of deaths. Understanding and tackling the impact of the virus has required a worldwide mobilisation and coordination of scientific research. The COVID-19 Data Portal (https://www.covid19dataportal.org/) was first released as part of the European COVID-19 Data Platform, on April 20th 2020 to facilitate rapid and open data sharing and analysis, to accelerate global SARS-CoV-2 and COVID-19 research. The COVID-19 Data Portal has fortnightly feature releases to continue to add new data types, search options, visualisations and improvements based on user feedback and research. The open datasets and intuitive suite of search, identification and download services, represent a truly FAIR (Findable, Accessible, Interoperable and Reusable) resource that enables researchers to easily identify and quickly obtain the key datasets needed for their COVID-19 research.

3'IsomiR Species Composition Affects Reliable Quantification of miRNA/isomiR Variants by Poly(A) RT-qPCR: Impact on Small RNA-Seq Profiling Validation.

Small RNA-sequencing (small RNA-seq) has revealed the presence of small RNA-naturally occurring variants such as microRNA (miRNA) isoforms or isomiRs. Due to their small size and the sequence similarity among miRNA isoforms, their validation by RT-qPCR is challenging. We previously identified two miR-31-5p isomiRs-the canonical and a 3'isomiR variant (3' G addition)-which were differentially expressed between individuals with azoospermia of different origin. Here, we sought to determine the discriminatory capacity between these two closely-related miRNA isoforms of three alternative poly(A) based-RT-qPCR strategies in both synthetic and real biological context. We found that these poly(A) RT-qPCR strategies exhibit a significant cross-reactivity between these miR-31-5p isomiRs which differ by a single nucleotide, compromising the reliable quantification of individual miRNA isoforms. Fortunately, in the biological context, given that the two miRNA variants show changes in the same direction, RT-qPCR results were consistent with the findings of small RNA-seq study. We suggest that miRNA selection for RT-qPCR validation should be performed with care, prioritizing those canonical miRNAs that, in small RNA-seq, show parallel/homogeneous expression behavior with their most prevalent isomiRs, to avoid confounding RT-qPCR-based results. This is suggested as the current best strategy for robust biomarker selection to develop clinically useful tests.

Influence of placebo effect in mental disorders research: A systematic review and meta-analysis.

BACKGROUND: Randomized controlled trials (RCT) in mental disorders research commonly use active control groups including psychotherapeutic shams or inactive medication. This meta-analysis assessed whether placebo conditions (active controls) had an effect compared to no treatment or usual care (passive controls). METHODS: PubMed, Scopus, PsycINFO, PsycARTICLES, Ovid, the Cochrane Central Register of Controlled Trials and Web of Science were searched from inception to April 2021 and reference lists of relevant articles. Three-arm RCTs, including active and passive control groups, were selected. Where individual standardized mean difference (SMD) was calculable, random effects meta-analyses were performed to estimate an overall effect size with 95% confidence intervals (CI) comparing active vs passive controls. Heterogeneity was assessed using I² statistic and meta-regression. Funnel asymmetry was evaluated using Egger's test (Prospero registration: CRD42021242940). RESULTS: 24 articles with 25 relevant RCTs were included in the review, of which 11 studies were of high risk of bias. There was an improvement in outcomes favouring the placebo conditions, compared to passive controls, overall (25 studies, SMD 0.24, 95% CI 0.06-0.42, I² = 43%) and in subgroups with anxiety (SMD 0.45, 95% CI 0.07-0.84, I² = 59%) or depression (SMD 0.22, 95% CI 0.04-0.39, I² = 0%). Meta-regression did not show a significant explanation for heterogeneity. Egger's test showed no asymmetry (p = .200). CONCLUSIONS: A small placebo effect was observed in mental disorders research overall, and in patients with anxiety or depression. These findings should be interpreted with caution in the light of heterogeneity and risk of bias.

Genome-wide compound heterozygote analysis highlights DPY19L2 alleles in a non-consanguineous Spanish family with total globozoospermia.

RESEARCH QUESTION: Would the use of genome-wide genotyping be an advantageous strategy to identify the molecular aetiology of two brothers from a non-consanguineous family, clinically diagnosed with total globozoospermia? DESIGN: Two related Spanish globozoospermic patients were studied. Eight first- and second-degree family members were also included in the study. The clinical procedure included anamnesis, physical examination and semen analyses. Acrosome visualization was performed by fluorescein isothiocyanate-Pisum sativum agglutinin labelling and ultrastructural electron microscope sperm analysis. Sperm DNA fragmentation was determined by TUNEL and SCD. Molecular analysis included: the detection of deletion of the DPY19L2 gene by a BPa (break point "a") gap-polymerase chain reaction, and genotyping by using a high-throughput genome-wide genotyping platform and a genotype imputation strategy. RESULTS: The biological characteristics of the two globozoospermic siblings included round-headed spermatozoa without an acrosome; ultrastructural defects in spermatozoa; increased sperm fragmentation and aneuploidies, inability of spermatozoa to activate oocytes (correctable with artificial activation) and good developmental potential of embryos generated by IVF/intracytoplasmic sperm injection. This genetic study focused on a genome-wide compound heterozygote analysis that identified two deleterious rare coding variants in the DPY19L2 gene [rs771726551 (c.431T>A exon 3) and rs147579680 (c.869G>A exon 8)]. CONCLUSION: A genome-wide compound heterozygote analysis strategy should be considered for molecular screening in globozoospermia and other rare congenital diseases, particularly in cases from non-consanguineous families.

Metagenomic analysis reveals differences in the co-occurrence and abundance of viral species in SARS-CoV-2 patients with different severity of disease.

BACKGROUND: SARS-CoV-2 infections have a wide spectrum of clinical manifestations whose causes are not completely understood. Some human conditions predispose to severe outcome, like old age or the presence of comorbidities, but many other facets, including coinfections with other viruses, remain poorly characterized. METHODS: In this study, the eukaryotic fraction of the respiratory virome of 120 COVID-19 patients was characterized through whole metagenomic sequencing. RESULTS: Genetic material from respiratory viruses was detected in 25% of all samples, whereas human viruses other than SARS-CoV-2 were found in 80% of them. Samples from hospitalized and deceased patients presented a higher prevalence of different viruses when compared to ambulatory individuals. Small circular DNA viruses from the Anneloviridae (Torque teno midi virus 8, TTV-like mini virus 19 and 26) and Cycloviridae families (Human associated cyclovirus 10), Human betaherpesvirus 6, were found to be significantly more abundant in samples from deceased and hospitalized patients compared to samples from ambulatory individuals. Similarly, Rotavirus A, Measles morbillivirus and Alphapapilomavirus 10 were significantly more prevalent in deceased patients compared to hospitalized and ambulatory individuals. CONCLUSIONS: Results show the suitability of using metagenomics to characterize a broader peripheric virological landscape of the eukaryotic virome in SARS-CoV-2 infected patients with distinct disease outcomes. Identified prevalent viruses in hospitalized and deceased patients may prove important for the targeted exploration of coinfections that may impact prognosis.

Cytokine profiles and the dynamic of gingivitis development in humans.

AIM: To investigate the relationship between cytokine profiles and "fast" and "slow" patterns of gingival inflammation development. MATERIALS AND METHODS: Forty-two adults participated in an experimental gingivitis study, comprising a 2-week hygiene phase (clinical examination and professional cleaning); a 3-week induction phase (absence of oral hygiene); and a 2-week resolution phase (re-establishment of oral hygiene). Plaque and gingival inflammation scores were assessed. Interferon-gamma (IFN-γ), interleukin (IL)-1ß, IL-2, IL-4, IL-6, IL-8, IL-10, IL-12p70, IL-13, and tumour necrosis factor-alpha (TNF-α) from gingival crevicular fluid were collected and measured by multiplex ELISA. Group-based-trajectory-modelling (GBTM) was used to model cytokine profiles over the induction phase. The effect of gingival inflammation on cytokine levels over time was estimated with mixed-effects modelling. RESULTS: GBTM analysis revealed two cytokine profiles, "non-organized response" (IL-4, IL-6, IL-8, IL-12, and IL-13) and "organized response" (IL-2, IL-10, and TNF-α). Among the "slow" responders, neither cytokine profile was associated with gingivitis. In contrast, a "fast" response was associated with a higher "non-organized response" factor (coef. 0.14) and a lower "organized response" factor (coef. -0.03). CONCLUSION: A "fast" gingivitis development was associated with a higher "non-organized response" and a lower "organized response", which may elucidate the role of individual variability in gingivitis susceptibility.

Women survivors of intimate partner violence talk about using e-health during pregnancy: a focus group study.

BACKGROUND: Pregnancy is a period of particular vulnerability to experience intimate partner violence against women (IPVAW). eHealth strategies have been implemented to identify women exposed to IPVAW and to combat the abuse and empower them, but there is a lack of evidence on the use of these strategies among pregnant women. This work aims to identify the needs, concerns and preferences of survivors about the use of eHealth strategies to counsel and empower pregnant victims of IPVAW in antenatal care. METHODS: A focus group of six IPVAW survivors who had been pregnant was conducted and open questions about the use of eHealth strategies were asked. The session was recorded, transcribed and thematically analyzed. We identified three main themes: needs and worries of pregnant women experiencing IPVAW, key aspects of video counseling sessions and usefulness of safety planning apps. RESULTS: Women highlighted the relevant role of healthcare professionals-especially midwives-in the identification of IPVAW and the wellbeing of their children as one of the main concerns. They perceived video counseling and safety planning apps as valuable resources. The preferred contents for a video counseling intervention were awareness-raising of the situation, self-esteem and legal advice. They also proposed safety and pregnant-related aspects that should be taken into account in the design of the video counseling sessions and the safety planning app. CONCLUSIONS: Video counseling sessions and safety planning apps are potentially useful tools to counsel and empower women who experience IPVAW during pregnancy. Midwives play a key role in this endeavor.

Is prophylactic mesh closure effective to decrease the incidence of incisional hernia after laparotomy in colorectal surgery?

BACKGROUND: few studies have studied prophylactic mesh closure after laparotomy for colorectal surgery. METHODS: a retrospective cohort study was performed to compare patients with and without prophylactic mesh closure after open colorectal surgery. RESULTS: 309 patients were included from January 2014 to December 2016. Prophylactic mesh closure was performed in 98 patients (31.7%). After a mean follow-up of 21.7 months, incisional hernia was developed in 9 and 54 patients in the group with and without mesh respectively (9.2% vs. 25.7%, OR = 0.3, p = 0.001). In the multivariate Cox model prophylactic mesh closure was associated with a protective effect on incisional hernia development with a Hazard Ratio of 0.46 (p = 0.033). Surgical site infection was more frequent in the mesh group (19.4% vs. 9.5%, OR = 2.3, p = 0.015). CONCLUSIONS: prophylactic mesh closure is effective to decrease the incidence of incisional hernia after colorectal surgery.

The ELIXIR Core Data Resources: fundamental infrastructure for the life sciences.

SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.

Trocar-site incisional hernia after laparoscopic colorectal surgery: a significant problem? Incidence and risk factors from a single-center cohort.

BACKGROUND: Trocar-site incisional hernia (TSIH) after laparoscopic surgery has been scarcely studied. TSIH incidence and risk factors have never been properly studied for laparoscopic colorectal surgery. METHODS: A retrospective analytic study in a tertiary hospital was performed including patients who underwent elective laparoscopic colorectal surgery between 2014 and 2016. Clinical and radiological TSIH were analyzed. RESULTS: 272 patients with a mean age of 70.7 years were included. 205 (75.4%) underwent surgery for a malignant disease. The most common procedure was right colectomy (108 patients, 39.7%). After a mean follow-up of 30.8 months 64 (23.5%) patients developed a TSIH. However, only 7 out of 64 (10.9%) patients with a TSIH underwent incisional hernia repair. That means that 2.6% of all the patients underwent TSIH repair. 44 (68.8%) patients had TSIH in the umbilical Hasson trocar. In the multivariate analysis, the existence of an umbilical Hasson trocar orifice was the only statistically significant risk factor for TSIH development. CONCLUSIONS: Incidence of TSIH was high, although few patients underwent incisional hernia repair. Most TSIH were observed in the umbilical Hasson trocar, which was the only risk factor for TSIH development in the multivariate analysis. Efforts should be addressed to avoid TSIH in the umbilical Hasson trocar.