Using EMBL-EBI Services via Web Interface and Programmatically via Web Services.

The European Bioinformatics Institute (EMBL-EBI)'s Job Dispatcher framework provides access to a wide range of core databases and analysis tools that are of key importance in bioinformatics. As well as providing web interfaces to these resources, web services are available using REST and SOAP protocols that enable programmatic access and allow their integration into other applications and analytical workflows and pipelines. This article describes the various options available to researchers and bioinformaticians who would like to use our resources via the web interface employing RESTful web services clients provided in Perl, Python, and Java or who would like to use Docker containers to integrate the resources into analysis pipelines and workflows. © 2024 The Authors. Current Protocols published by Wiley Periodicals LLC. Basic Protocol 1: Retrieving data from EMBL-EBI using Dbfetch via the web interface Alternate Protocol 1: Retrieving data from EMBL-EBI using WSDbfetch via the REST interface Alternate Protocol 2: Retrieving data from EMBL-EBI using Dbfetch via RESTful web services with Python client Support Protocol 1: Installing Python REST web services clients Basic Protocol 2: Sequence similarity search using FASTA search via the web interface Alternate Protocol 3: Sequence similarity search using FASTA via RESTful web services with Perl client Support Protocol 2: Installing Perl REST web services clients Basic Protocol 3: Sequence similarity search using NCBI BLAST+ RESTful web services with Python client Basic Protocol 4: Sequence similarity search using HMMER3 phmmer REST web services with Perl client and Docker Support Protocol 3: Installing Docker and running the EMBL-EBI client container Basic Protocol 5: Protein functional analysis using InterProScan 5 RESTful web services with the Python client and Docker Alternate Protocol 4: Protein functional analysis using InterProScan 5 RESTful web services with the Java client Support Protocol 4: Installing Java web services clients Basic Protocol 6: Multiple sequence alignment using Clustal Omega via web interface Alternate Protocol 5: Multiple sequence alignment using Clustal Omega with Perl client and Docker Support Protocol 5: Exploring the RESTful API with OpenAPI User Inferface.

Dental service use among adults with incident type 2 diabetes, rheumatoid arthritis or inflammatory bowel disease.

OBJECTIVES: It is not clear if or how the incidence of systemic conditions like type 2 diabetes mellitus (DM2), rheumatoid arthritis (RA) or inflammatory bowel disease (IBD) affects dental service utilization. Using nationwide Danish register data, the aim of this study was to analyse the use of dental services 7 years before and after being diagnosed with DM2, RA or IBD between 1997 and 2011. METHODS: Information about incident DM2 was obtained from the National Diabetes Register, and incident RA and IBD were defined based on diagnosis codes of hospital contacts identified through the National Patient Register. Separately, for each of the three conditions, each individual with the incident condition was matched to one control individual based on age, gender, country of origin, municipality of residence, highest completed education, the main source of income and income using coarsened exact matching in the year of incidence. The use of dental services and treatments received within each calendar year from 7 years before to 7 years after getting the condition were analysed with generalized estimating equations. RESULTS: People with incident DM2 were less likely (by seven percentage points) to be dental service users within a year than people without incident DM2 for a period extending from up to 7 years prior to 7 years after the diagnosis. This difference even slightly increased after the diagnosis. Those with incident IBD exhibited a consistently but modestly higher proportion of dental service use (three percentage points) than those without incident IBD before and after the diagnosis. Differences in the use of services between those with or without incident RA were minor. For all three systemic diseases, detected differences mainly mirrored differences in the provision of supragingival scaling and restorative treatment. CONCLUSIONS: The findings suggest that the impact of these three systemic conditions on dental service use was minor.

Birth weight, growth indices, and seminal parameters in male offspring are resilient features to maternal pre-conceptional dietary manipulation in sheep.

Gestational diet manipulation can lead to inadequate fetal nutrient supply resulting in low birth weight, limited postnatal growth, and consequently, reduced reproductive performance in the progeny. However, effects of short-term maternal pre-conceptional dietary manipulation on postnatal growth and reproductive parameters of male offspring in large animals remains unexplored. To determine these consequences, female crossbred (Polypay x Dorset) sheep were allocated to three groups (n = 33/group) of dietary manipulation for 21 days prior to mating under the following conditions: (1) control at 100 % of maintenance energy requirements (40 Kcal of metabolizable energy/kg body weight [BW]), (2) undernutrition (UN) at 50 % of Control intake, and (3) overnutrition (ON) at 200 % of maintenance energy. Singleton ram lambs (UN:9; C:12; ON:6) were monitored from birth until 8 months of age, including birth weight, weekly weights, weight gain, body mass index (BMI), and circulating testosterone. After weaning, monthly scrotal circumference and subcutaneous fat depth were measured. Semen morphology and motility were evaluated at 7 and 8 months of age. Birth weight, weight gain, and BMI at birth and weaning were not significantly different among nutritional treatments. None of the pre-conceptional diets affected body weight change from weaning until 36 weeks of age, BMI, fat depth, or scrotal circumference across the experiment. A sustained rise in plasma testosterone concentrations was detected when ram lambs were, on average, 82 days old and 37 kg. Both testosterone concentrations and scrotal circumference were positively correlated to body weight regardless of treatment group. In addition, seminal parameters did not differ among treatments, but a transient increase in plasma testosterone at 18 weeks of age was observed in ON ram lambs compared to control rams. In conclusion, birth weight, growth indices, and seminal parameters in singleton rams are resilient features in the progeny upon maternal pre-conceptional dietary manipulation in sheep.

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.

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.

Exploration of low-frequency allelic variants of SARS-CoV-2 genomes reveals coinfections in Mexico occurred during periods of VOCs turnover.

A total of 14 973 alleles in 29 661 sequenced samples collected between March 2021 and January 2023 by the Mexican Consortium for Genomic Surveillance (CoViGen-Mex) and collaborators were used to construct a thorough map of mutations of the Mexican SARS-CoV-2 genomic landscape containing Intra-Patient Minor Allelic Variants (IPMAVs), which are low-frequency alleles not ordinarily present in a genomic consensus sequence. This additional information proved critical in identifying putative coinfecting variants included alongside the most common variants, B.1.1.222, B.1.1.519, and variants of concern (VOCs) Alpha, Gamma, Delta, and Omicron. A total of 379 coinfection events were recorded in the dataset (a rate of 1.28 %), resulting in the first such catalogue in Mexico. The most common putative coinfections occurred during the spread of Delta or after the introduction of Omicron BA.2 and its descendants. Coinfections occurred constantly during periods of variant turnover when more than one variant shared the same niche and high infection rate was observed, which was dependent on the local variants and time. Coinfections might occur at a higher frequency than customarily reported, but they are often ignored as only the consensus sequence is reported for lineage identification.

A microglia clonal inflammatory disorder in Alzheimer's Disease.

Somatic genetic heterogeneity resulting from post-zygotic DNA mutations is widespread in human tissues and can cause diseases, however few studies have investigated its role in neurodegenerative processes such as Alzheimer's Disease (AD). Here we report the selective enrichment of microglia clones carrying pathogenic variants, that are not present in neuronal, glia/stromal cells, or blood, from patients with AD in comparison to age-matched controls. Notably, microglia-specific AD-associated variants preferentially target the MAPK pathway, including recurrent CBL ring-domain mutations. These variants activate ERK and drive a microglia transcriptional program characterized by a strong neuro-inflammatory response, both in vitro and in patients. Although the natural history of AD-associated microglial clones is difficult to establish in human, microglial expression of a MAPK pathway activating variant was previously shown to cause neurodegeneration in mice, suggesting that AD-associated neuroinflammatory microglial clones may contribute to the neurodegenerative process in patients.

Epidemiological changes in invasive Streptococcus pyogenes infection during the UK alert period: A molecular comparative analysis from a tertiary Spanish hospital in 2023.

OBJECTIVES: To study the genomic epidemiology of Streptococcus pyogenes causing bloodstream infections (GAS-BSI) in a Spanish tertiary hospital during the United Kingdom invasive S. pyogenes outbreak alert. METHODS: Retrospective epidemiological analysis of GAS-BSI during the January-May 2017-2023 period. WGS was performed using Ion torrent GeneStudio™ S5 system for emm typing and identification of superantigen genes in S. pyogenes isolated during the 2022-2023 UK outbreak alert. RESULTS: During 2023, there were more cases of GAS-BSI compared to the same period of previous year with a non-significant increase in children. Fourteen isolates were sequenced. The emm1 (6/14, 42.9%) and emm12 (2/14, 14.3%) types predominated; 5 of 6 (75%) emm1 isolates were from the M1UK clone. The most detected superantigen genes were speG (12/14, 85.7%), speC (10/14, 71.4%), speJ (7/14, 50%), and speA (5/15, 33.3%). speA and speJ were predominant in M1UK clone. CONCLUSIONS: Our genomic epidemiology in 2023 is similar to the reported data from the UK outbreak alert in the same period and different from previous national S. pyogenes surveillance reports.

Contesting the conventional wisdom of periodontal risk assessment.

Over the years, several reviews of periodontal risk assessment tools have been published. However, major misunderstandings still prevail in repeated attempts to use these tools for prognostic risk prediction. Here we review the principles of risk prediction and discuss the value and the challenges of using prediction models in periodontology. Most periodontal risk prediction models have not been properly developed according to guidance given for the risk prediction model development. This shortcoming has led to several problems, including the creation of arbitrary risk scores. These scores are often labelled as 'high risk' without explicit boundaries or thresholds for the underlying continuous risk estimates of patient-important outcomes. Moreover, it is apparent that prediction models are often misinterpreted as causal models by clinicians and researchers although they cannot be used as such. Additional challenges like the critical assessment of transportability and applicability of these prediction models, as well as their impact on clinical practice and patient outcomes, are not considered in the literature. Nevertheless, these instruments are promoted with claims regarding their ability to deliver more individualized and precise periodontitis treatment and prevention, purportedly resulting in improved patient outcomes. However, people with or without periodontitis deserve proper information about their risk of developing patient-important outcomes such as tooth loss or pain. The primary objective of disseminating such information should not be to emphasize assumed treatment efficacy, hype individualization of care, or promote business interests. Instead, the focus should be on providing individuals with locally validated and regularly updated predictions of specific risks based on readily accessible and valid key predictors (e.g. age and smoking).

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.

Epidemiological changes in invasive Streptococcus pyogenes infection during the UK alert period: A molecular comparative analysis from a tertiary Spanish hospital in 2023

Objectives: To study the genomic epidemiology of Streptococcus pyogenes causing bloodstream infections (GAS-BSI) in a Spanish tertiary hospital during the United Kingdom invasive S. pyogenes outbreak alert. Methods: Retrospective epidemiological analysis of GAS-BSI during the January–May 2017–2023 period. WGS was performed using Ion torrent GeneStudio™ S5 system for emm typing and identification of superantigen genes in S. pyogenes isolated during the 2022–2023 UK outbreak alert. Results: During 2023, there were more cases of GAS-BSI compared to the same period of previous year with a non-significant increase in children. Fourteen isolates were sequenced. The emm1 (6/14, 42.9%) and emm12 (2/14, 14.3%) types predominated; 5 of 6 (75%) emm1 isolates were from the M1UK clone. The most detected superantigen genes were speG (12/14, 85.7%), speC (10/14, 71.4%), speJ (7/14, 50%), and speA (5/15, 33.3%). speA and speJ were predominant in M1UK clone. Conclusions: Our genomic epidemiology in 2023 is similar to the reported data from the UK outbreak alert in the same period and different from previous national S. pyogenes surveillance reports.(AU)

Objetivos: Estudiar la epidemiología genómica de aislados de Streptococcus pyogenes causantes de bacteriemia (GAS-BSI) en un hospital de tercer nivel español durante la alerta por incremento de infecciones invasivas por S. pyogenes en el Reino Unido. Métodos: Análisis epidemiológico retrospectivo de GAS-BSI durante el periodo enero-mayo 2017-2023. Se realizó una secuenciación de genoma completo con el sistema Ion torrent GeneStudio™ S5 de los aislados obtenidos durante la alerta de brote del Reino Unido 2022-2023 para tipificación emm e identificación de genes de superantígenos. Resultados: Durante el periodo enero-mayo de 2023 hubo más casos de GAS-BSI que en el mismo periodo de años anteriores con un aumento no significativo en niños. Se secuenciaron 14 aislados. Predominaron los tipos emm1 (6/14, 42,9%) y emm12 (2/14, 14,3%); 5 de 6 (75%) aislados emm1 eran del clon M1UK. Los genes de superantígenos más detectados fueron speG (12/14, 85,7%), speC (10/14, 71,4%), speJ (7/14, 50%) y speA (5/15, 33,3%). Los genes speA y speJ predominaron en el clon M1UK. Conclusiones: Nuestra epidemiología genómica de Streptococcus pyogenes causantes de bacteriemia en 2023 es similar a los datos comunicados por el Reino Unido durante el mismo periodo y diferente de los informes nacionales previos de vigilancia.(AU)

Seminal extracellular vesicle sncRNA sequencing reveals altered miRNA/isomiR profiles as sperm retrieval biomarkers for azoospermia.

BACKGROUND: Non-invasive molecular biomarkers for classifying azoospermia by origin into either obstructive or non-obstructive/secretory azoospermia, as well as for inferring the spermatogenic reserve of the testis of non-obstructive/secretory azoospermia patients, are of great interest for testicular sperm retrieval outcome prediction for assisted reproduction. Prior analyses of semen small non-coding RNA expression in azoospermia have focused on microRNAs, but there has been a lack of attention on other regulatory small RNA species. In this regard, studying more in-depth expression changes of small non-coding RNA subtypes in small extracellular vesicles from semen of azoospermic individuals could be useful to select additional non-invasive biomarkers with diagnostic/prognostic purposes. MATERIAL AND METHODS: A high-throughput small RNA profiling analysis to determine the expression pattern of seminal small extracellular vesicle microRNAs (analyzed at the isomiR level), PIWI-interacting RNAs, and transfer RNA-derived small RNAs in normozoospermic (n = 4) and azoospermic (obstructive azoospermia because of pathological occurring obstruction in the genital tract, n = 4; secretory azoospermic individuals with positive testicular sperm extraction value, n = 5; secretory azoospermic individuals with negative testicular sperm extraction value, n = 4) individuals was carried out. Reverse transcriptase-quantitative real-time polymerase chain reaction validation analysis of selected microRNAs was additionally performed in a larger number of individuals. RESULTS AND DISCUSSION: Clinically relevant quantitative changes in the small non-coding RNA levels contained in semen small extracellular vesicles can be used as biomarkers for the origin of azoospermia and for predicting the presence of residual spermatogenesis. In this regard, canonical isoform microRNAs (n = 185) but also other isomiR variants (n = 238) stand out in terms of numbers and fold-change differences in expression, underlining the need to consider isomiRs when investigating microRNA-based regulation. Conversely, although transfer RNA-derived small RNAs are shown in our study to represent a high proportion of small non-coding RNA sequences in seminal small extracellular vesicle samples, they are not able to discriminate the origin of azoospermia. PIWI-interacting RNA cluster profiles and individual PIWI-interacting RNAs with significant differential expression were also not able to discriminate. Our study demonstrated that expression values of individual and/or combined canonical isoform microRNAs (miR-10a-5p, miR-146a-5p, miR-31-5p, miR-181b-5p; area under the receiver operating characteristic curve >0.8) in small extracellular vesicles provide considerable clinical value in identifying samples with a high likelihood of sperm retrieval while discriminating azoospermia by origin. Although no individual microRNA showed sufficient discriminating power on its own to identify severe spermatogenic disorders with focal spermatogenesis, multivariate microRNA models in semen small extracellular vesicles have the potential to identify those individuals with residual spermatogenesis. Availability and adoption of such non-invasive molecular biomarkers would represent a great improvement in reproductive treatment decision protocols for azoospermia in clinical practice.

SARS-CoV-2 Omicron variants BA.4 and BA.5 dominated the fifth COVID-19 epidemiological wave in Mexico.

In Mexico, the BA.4 and BA.5 Omicron variants dominated the fifth epidemic wave (summer 2022), superseding BA.2, which had circulated during the inter-wave period. The present study uses genome sequencing and statistical and phylogenetic analyses to examine these variants' abundance, distribution, and genetic diversity in Mexico from April to August 2022. Over 35 % of the sequenced genomes in this period corresponded to the BA.2 variant, 8 % to the BA.4 and 56 % to the BA.5 variant. Multiple subvariants were identified, but the most abundant, BA.2.9, BA.2.12.1, BA.5.1, BA.5.2, BA.5.2.1 and BA.4.1, circulated across the entire country, not forming geographical clusters. Contrastingly, other subvariants exhibited a geographically restricted distribution, most notably in the Southeast region, which showed a distinct subvariant dynamic. This study supports previous results showing that this region may be a significant entry point and contributed to introducing and evolving novel variants in Mexico. Furthermore, a differential distribution was observed for certain subvariants among specific States through time, which may have contributed to the overall increased diversity observed during this wave compared to the previous ones. This study highlights the importance of sustaining genomic surveillance to identify novel variants that may impact public health.

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.

PLATE: A perception-latency aware estimator.

Target tracking is a popular problem with many potential applications. There has been a lot of effort on improving the quality of the detection of targets using cameras through different techniques. In general, with higher computational effort applied, i.e., a longer perception-latency, a better detection accuracy is obtained. However, it is not always useful to apply the longest perception-latency allowed, particularly when the environment does not require to and when the computational resources are shared between other tasks. In this work, we propose a new Perception-LATency aware Estimator (PLATE), which uses different perception configurations in different moments of time in order to optimize a certain performance measure. This measure takes into account a perception-latency and accuracy trade-off aiming for a good compromise between quality and resource usage. Compared to other heuristic frame-skipping techniques, PLATE comes with a formal complexity and optimality analysis. The advantages of PLATE are verified by several experiments including an evaluation over a standard benchmark with real data and using state of the art deep learning object detection methods for the perception stage.

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.

Expression and localization of vascular endothelial growth factor and its receptors in the pig uterus during peri-implantation and determination of the in vitro effect of the angiogenesis inhibitor SU5416 on VEGF system expression.

The aim of this work was to determine endometrial mRNA expression and uterine protein localization of vascular endothelial growth factor (VEGF) and its receptors VEGFR1 and VEGFR2 during the estrous cycle and peri-implantation period in sows. Uterine tissues were collected from pregnant sows on days 12, 14, 16, and 18 after artificial insemination and from non-pregnant animals on days 2 and 12 of the estrous cycle (day 0 = day of estrus). Using immunohistochemistry, a positive signal for VEGF and its receptor VEGFR2 was found in uterine luminal epithelial cells, endometrial glands, stroma, blood vessels, and myometrium. A VEGFR1 signal was only found in endometrial and myometrial blood vessels and stroma. By day 18 of gestation, the mRNA expression levels of VEGF, VEGFR1, and VEGFR2 were higher than those observed on days 2 and 12 of the estrous cycle and on days 12, 14, and 16 of gestation. Then, a primary culture of sow endometrial epithelial cells was established to define the potential of the selective inhibition of VEGFR2 after treatment with inhibitor SU5416 and determine its effects on the expression pattern of the VEGF system. The endometrial epithelial cells treated with SU5416 showed a dose-dependent decrease in VEGFR1 and VEGFR2 mRNA expression. The present study provides additional evidence on the importance of the VEGF system during peri-implantation, as well as on the specific inhibitory activity of SU5416 in epithelial cells, which, as demonstrated, express the protein and mRNA of VEGF and its receptors VEGFR1 and VEGFR2.

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.

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.

The role of SPECT/CT in painful, noninfected knees after knee arthroplasty: a systematic review and meta-analysis-a diagnostic test accuracy review.

PURPOSE: The aim of this systematic review was to present the current evidence on the clinical use of single-photon emission computed tomography/computed tomography (SPECT/CT) in the evaluation of noninfected painful knees after knee arthroplasty. METHODS: Embase, PubMed, Google Scholar, Ovid, Scopus, Science Direct and the Cochrane Database of Systematic Reviews were searched from database inception to May 2022 following the PRISMA guidelines. As a primary outcome, we defined the role of SPECT/CT in the diagnostic approach to noninfected painful knee arthroplasty; as a secondary objective, we described the noninfection-related factors linked to painful knee arthroplasty. Pooled sensitivity, specificity, positive likelihood ratio, negative likelihood ratio, diagnostic odds ratio values and other indicators were calculated; receiver operating characteristic (ROC) curve analysis results and a summary of the areas under the curve (AUCs) from the included studies were reported. A Fagan plot, likelihood ratio plot and Deeks' funnel plot were generated and analysed. Methodological quality was assessed using the QUADAS-2 tool, and the certainty of evidence was assessed by the GRADE approach. RESULTS: A total of 493 publications were identified, of which eight met the inclusion criteria, with a final pooled sample size of 308 patients. The pooled sensitivity and specificity of SPECT/CT in diagnosing the source of pain in painful knee prostheses were 0.86 (95% CI: 0.75-0.93) and 0.90 (95% CI: 0.79-0.96), respectively, with pooled +LR and -LR values of 8.9 (95% CI: 4.11-19.19) and 0.15 (95% CI: 0.09-0.28). The pooled diagnostic odds ratio was 57.35, and the area under the curve was 0.94. SPECT/CT highly accurately identified different sources of pain, such as loosening of the prosthetic components, patellofemoral overloading, instability, malalignment of the components and degeneration of the patellofemoral compartment. The confidence of the estimates was moderate according to the GRADE approach. CONCLUSION: With demonstrated high sensitivity and specificity, as a diagnostic tool, SPECT/CT can identify the source of pain in painful knees after knee arthroplasty, particularly in cases of loosening, patellofemoral disorders and component malalignment (level of evidence III). These findings have significant clinical repercussions, such as in changing the initial diagnosis, identifying or excluding different causes of painful knee arthroplasties, guiding subsequent treatment and positively impacting the final clinical outcome. We moderately recommend the use of SPECT/CT for identifying the source of pain after knee arthroplasty according to the GRADE assessment. This review was preregistered in Prospero under code CRD42022320457.