Integrative analysis of multi-omics data reveals importance of collagen and the PI3K AKT signalling pathway in CAKUT.

Congenital Anomalies of the Kidney and Urinary Tract (CAKUT) is the leading cause of childhood chronic kidney failure and a significant cause of chronic kidney disease in adults. Genetic and environmental factors are known to influence CAKUT development, but the currently known disease mechanism remains incomplete. Our goal is to identify affected pathways and networks in CAKUT, and thereby aid in getting a better understanding of its pathophysiology. With this goal, the miRNome, peptidome, and proteome of over 30 amniotic fluid samples of patients with non-severe CAKUT was compared to patients with severe CAKUT. These omics data sets were made findable, accessible, interoperable, and reusable (FAIR) to facilitate their integration with external data resources. Furthermore, we analysed and integrated the omics data sets using three different bioinformatics strategies: integrative analysis with mixOmics, joint dimensionality reduction and pathway analysis. The three bioinformatics analyses provided complementary features, but all pointed towards an important role for collagen in CAKUT development and the PI3K-AKT signalling pathway. Additionally, several key genes (CSF1, IGF2, ITGB1, and RAC1) and microRNAs were identified. We published the three analysis strategies as containerized workflows. These workflows can be applied to other FAIR data sets and help gaining knowledge on other rare diseases.

Social Anxiety Profiles and Psychopathological Symptom Differences in Spanish Adolescents.

Research on social anxiety (SA) over the years has revealed its associations with different psychopathological symptoms. This study aims to characterize SA profiles in a sample of Spanish adolescents and explore their differences in psychopathological symptoms. Data from 1,288 Spanish students in the 15 to 18 age range (M = 16.30, SD = 0.97, 47.5% female) were collected using random cluster sampling. The Social Anxiety Scale for Adolescents (SAS-A) and the Symptom Assessment-45 Questionnaire (SA-45) were employed. Four SA profiles were revealed by the Latent Profile Analysis (LPA): extreme SA, high SA, moderate SA, and low SA. Statistically significant differences in psychopathological symptoms were revealed by the MANOVA (effect sizes from d = -2.13 to d = -0.37). The extreme SA profile exhibited the most severe psychopathological symptoms, whereas the low SA profile displayed the mildest manifestations. Proposed interventions aim to support adolescents with SA risk profiles.

Recording provenance of workflow runs with RO-Crate.

Recording the provenance of scientific computation results is key to the support of traceability, reproducibility and quality assessment of data products. Several data models have been explored to address this need, providing representations of workflow plans and their executions as well as means of packaging the resulting information for archiving and sharing. However, existing approaches tend to lack interoperable adoption across workflow management systems. In this work we present Workflow Run RO-Crate, an extension of RO-Crate (Research Object Crate) and Schema.org to capture the provenance of the execution of computational workflows at different levels of granularity and bundle together all their associated objects (inputs, outputs, code, etc.). The model is supported by a diverse, open community that runs regular meetings, discussing development, maintenance and adoption aspects. Workflow Run RO-Crate is already implemented by several workflow management systems, allowing interoperable comparisons between workflow runs from heterogeneous systems. We describe the model, its alignment to standards such as W3C PROV, and its implementation in six workflow systems. Finally, we illustrate the application of Workflow Run RO-Crate in two use cases of machine learning in the digital image analysis domain.

The European Reference Genome Atlas: piloting a decentralised approach to equitable biodiversity genomics.

A genomic database of all Earth's eukaryotic species could contribute to many scientific discoveries; however, only a tiny fraction of species have genomic information available. In 2018, scientists across the world united under the Earth BioGenome Project (EBP), aiming to produce a database of high-quality reference genomes containing all ~1.5 million recognized eukaryotic species. As the European node of the EBP, the European Reference Genome Atlas (ERGA) sought to implement a new decentralised, equitable and inclusive model for producing reference genomes. For this, ERGA launched a Pilot Project establishing the first distributed reference genome production infrastructure and testing it on 98 eukaryotic species from 33 European countries. Here we outline the infrastructure and explore its effectiveness for scaling high-quality reference genome production, whilst considering equity and inclusion. The outcomes and lessons learned provide a solid foundation for ERGA while offering key learnings to other transnational, national genomic resource projects and the EBP.

EXPRESS: Landmark Publications in Analytical Atomic Spectrometry: Fundamentals and Instrumentation Development.

The almost-two-centuries history of spectrochemical analysis has generated a body of literature so vast that it has become nearly intractable for experts, much less for those wishing to enter the field. Authoritative, focused reviews help to address this problem but become so granular that the overall directions of the field are lost. This broader perspective can be provided partially by general overviews but then the thinking, experimental details, theoretical underpinnings and instrumental innovations of the original work must be sacrificed. In the present compilation, this dilemma is overcome by assembling the most impactful publications in the area of analytical atomic spectrometry. Each entry was proposed by at least one current expert in the field and supported by a narrative that justifies its inclusion. The entries were then assembled into a coherent sequence and returned to contributors for a round-robin review.

sp2-Iminosugar azobenzene O-glycosides: Light-sensitive glycosidase inhibitors with unprecedented tunability and switching factors.

The conventional approach to developing light-sensitive glycosidase activity regulators, involving the combination of a glycomimetic moiety and a photoactive azobenzene module, results in conjugates with differences in glycosidase inhibitory activity between the interchangeable E and Z-isomers at the azo group that are generally below one-order of magnitude. In this study, we have exploited the chemical mimic character of sp2-iminosugars to access photoswitchable p- and o-azobenzene α-O-glycosides based on the gluco-configured representative ONJ. Notably, we achieved remarkably high switching factors for glycosidase inhibition, favoring either the E- or Z-isomer depending on the aglycone structure. Our data also indicate a correlation between the isomeric state of the azobenzene module and the selectivity towards α- and ß-glucosidase isoenzymes. The most effective derivative reached over a 103-fold higher inhibitory potency towards human ß-glucocerebrosidase in the Z as compared with the E isomeric form. This sharp contrast is compatible with ex-vivo activation and programmed self-deactivation at physiological temperatures, positioning it as a prime candidate for pharmacological chaperone therapy in Gaucher disease. Additionally, our results illustrate that chemical tailoring enables the engineering of photocommutators with the ability to toggle inhibition between α- and ß-glucosidase enzymes in a reversible manner, thus expanding the versatility and potential therapeutic applications of this approach.

Crystal Nucleation in Supercooled Atomic Liquids.

The liquid-to-solid phase transition is a complex process that is difficult to investigate experimentally with sufficient spatial and temporal resolution. A key aspect of the transition is the formation of a critical seed of the crystalline phase in a supercooled liquid, that is, a liquid in a metastable state below the melting temperature. This stochastic process is commonly described within the framework of classical nucleation theory, but accurate tests of the theory in atomic and molecular liquids are challenging. Here, we employ femtosecond x-ray diffraction from microscopic liquid jets to study crystal nucleation in supercooled liquids of the rare gases argon and krypton. Our results provide stringent limits to the validity of classical nucleation theory in atomic liquids, and offer the long-sought possibility of testing nonclassical extensions of the theory.

Pulsed Electric Field (PEF) treatment of progressive non-small cell lung cancer concurrently treated with immune checkpoint blockade: A case report.

Pulsed Electric Field (PEF) energy was delivered at the time of confirmational biopsy to ablate recurrent NSCLC in the right upper lobe (RUL) of the lung after recurrence while on durvalumab consolidation. The patient tolerated the procedure and exhibited stable disease at 6 and 12 months from time of durvalumab discontinuation and PEF treatment, respectively. This report represents the first use of the Aliya™ PEF system as a minimally invasive modality with potential to re-sensitize disease to immune checkpoint blockade (ICB) upon progression. Clinicaltrialsgov identifier: NCT04773275.

Controlled silver electrodeposition on gold nanoparticle antibody tags for ultrasensitive prostate specific antigen sensing using electrochemical and optical smartphone detection.

One of the current challenges in medicine is to achieve a rapid and unequivocal detection and quantification of extremely low levels of disease biomarkers in complex biological samples. Here, we present the development and analytical evaluation of a low-cost smartphone-based system designed for ultrasensitive detection of the prostate-specific antigen (PSA) using two detection alternatives: electrochemical or optical, by coupling the smartphone with a portable potentiostat or magnifying lenses. An antibody tagged with gold nanoparticles (AuNPs), and indium tin oxide coated polyethylene terephthalate platform (ITO-PET) have been used to develop a sandwich-type immunoassay. Then, a controlled silver electrodeposition on the AuNPs surface is carried out, enhancing their size greatly. Due to such strong nanoparticle-size amplification (from nm to µm), the final detection can be dual, by measuring current intensity or the number of silver-enlarged microstructures generated. The proposed strategies exhibited limit detections (LOD) of 102 and 37 fg/mL for electrochemical and optical detection respectively. The developed immunosensor reaches excellent selectivity and performance characteristics to quantify biomarkers at clinically relevant values without any pretreatment. These proposed procedures could be useful to check and verify possible recurrence after clinical treatment of tumors or even report levels of disease serum biomarkers in early stages.

Progress and Challenge of Sensors for Dairy Food Safety Monitoring.

One of the most consumed foods is milk and milk products, and guaranteeing the suitability of these products is one of the major concerns in our society. This has led to the development of numerous sensors to enhance quality controls in the food chain. However, this is not a simple task, because it is necessary to establish the parameters to be analyzed and often, not only one compound is responsible for food contamination or degradation. To attempt to address this problem, a multiplex analysis together with a non-directed (e.g., general parameters such as pH) analysis are the most relevant alternatives to identifying the safety of dairy food. In recent years, the use of new technologies in the development of devices/platforms with optical or electrochemical signals has accelerated and intensified the pursuit of systems that provide a simple, rapid, cost-effective, and/or multiparametric response to the presence of contaminants, markers of various diseases, and/or indicators of safety levels. However, achieving the simultaneous determination of two or more analytes in situ, in a single measurement, and in real time, using only one working 'real sensor', remains one of the most daunting challenges, primarily due to the complexity of the sample matrix. To address these requirements, different approaches have been explored. The state of the art on food safety sensors will be summarized in this review including optical, electrochemical, and other sensor-based detection methods such as magnetoelastic or mass-based sensors.

Trehalose-polyamine/DNA nanocomplexes: impact of vector architecture on cell and organ transfection selectivity.

A novel family of precision-engineered gene vectors with well-defined structures built on trehalose and trehalose-based macrocycles (cyclotrehalans) comprising linear or cyclic polyamine heads have been synthesized through procedures that exploit click chemistry reactions. The strategy was conceived to enable systematic structural variations and, at the same time, ensuring that enantiomerically pure vectors are obtained. Notably, changes in the molecular architecture translated into topological differences at the nanoscale upon co-assembly with plasmid DNA, especially regarding the presence of regions with short- or long-range internal order as observed by TEM. In vitro and in vivo experiments further evidenced a significant impact on cell and organ transfection selectivity. Altogether, the results highlight the potential of trehalose-polyamine/pDNA nanocomplex monoformulations to achieve targeting transfection without the need for any additional cell- or organ-sorting component.

High-Mannose Oligosaccharide Hemimimetics that Recapitulate the Conformation and Binding Mode to Concanavalin A, DC-SIGN and Langerin.

The "carbohydrate chemical mimicry" exhibited by sp2 -iminosugars has been utilized to develop practical syntheses for analogs of the branched high-mannose-type oligosaccharides (HMOs) Man3 and Man5 . In these compounds, the terminal nonreducing Man residues have been substituted with 5,6-oxomethylidenemannonojirimycin (OMJ) motifs. The resulting oligomannoside hemimimetic accurately reproduce the structure, configuration, and conformational behavior of the original mannooligosaccharides, as confirmed by NMR and computational techniques. Binding studies with mannose binding lectins, including concanavalin A, DC-SIGN, and langerin, by enzyme-linked lectin assay and surface plasmon resonance revealed significant variations in their ability to accommodate the OMJ unit in the mannose binding site. Intriguingly, OMJMan segments demonstrated "in line" heteromultivalent effects during binding to the three lectins. Similar to the mannobiose (Man2 ) branches in HMOs, the binding modes involving the external or internal monosaccharide unit at the carbohydrate binding-domain exist in equilibrium, facilitating sliding and recapture processes. This equilibrium, which influences the multivalent binding of HMOs, can be finely modulated upon incorporation of the OMJ sp2 -iminosugar caps. As a proof of concept, the affinity and selectivity towards DC-SIGN and langerin were adjustable by presenting the OMJMan epitope in platforms with diverse architectures and valencies.

WOMBAT-P: Benchmarking Label-Free Proteomics Data Analysis Workflows.

The inherent diversity of approaches in proteomics research has led to a wide range of software solutions for data analysis. These software solutions encompass multiple tools, each employing different algorithms for various tasks such as peptide-spectrum matching, protein inference, quantification, statistical analysis, and visualization. To enable an unbiased comparison of commonly used bottom-up label-free proteomics workflows, we introduce WOMBAT-P, a versatile platform designed for automated benchmarking and comparison. WOMBAT-P simplifies the processing of public data by utilizing the sample and data relationship format for proteomics (SDRF-Proteomics) as input. This feature streamlines the analysis of annotated local or public ProteomeXchange data sets, promoting efficient comparisons among diverse outputs. Through an evaluation using experimental ground truth data and a realistic biological data set, we uncover significant disparities and a limited overlap in the quantified proteins. WOMBAT-P not only enables rapid execution and seamless comparison of workflows but also provides valuable insights into the capabilities of different software solutions. These benchmarking metrics are a valuable resource for researchers in selecting the most suitable workflow for their specific data sets. The modular architecture of WOMBAT-P promotes extensibility and customization. The software is available at https://github.com/wombat-p/WOMBAT-Pipelines.

A plasmonic MNAzyme signal amplification strategy for quantification of miRNA-4739 breast cancer biomarker.

A major challenge in the 21st century is the development of point-of-care diagnostic tools capable to detect and quantify disease biomarkers in a straightforward, affordable, sensitive, and specific manner. The remarkable plasmonic properties of gold nanoparticles (AuNPs) have promoted their use for development of simple methodologies for nucleic acid detection in combination with a variety of oligonucleotides amplification techniques. Here, assemblies of AuNPs with Multicomponent Nucleic Acid enzymes (MNAzymes) has been successfully used in the design of a highly sensitive and simple bioassay for rapid spectroscopic detection and quantification of miRNA-4739 in blood samples. The miRNA selected is a doxorubicin chemoresistant biomarker in breast cancer which overexpression promotes the proliferation, progression, and survival of cancer cells. In this work, two alternatives experimental designs, based on use of MNAzymes and AuNPs, have been optimized and applied for sensitive miRNA-4739 quantification: one based on a traditional direct measurement of wavelength shift and a second non-conventional simple approach based on isolation and measurement of free nanoparticles absorbance. Improvement in sensitivity and, higher measurement accuracy and precision were achieved with the second approach. The developed bioassay provides a detection limit as low as 7 pmolL-1 for miRNA-4739 quantification and performed satisfactory selectivity and well practical applicability by analysis of the miRNA-4739 in blood, demonstrating that the proposed strategy is a promising and suitable spectroscopic method for breast cancer diagnosis thought liquid biopsy of circulating tumoral cells.

A bibliometric analysis on adolescent social anxiety and psychoeducational variables in Web of Science 2002-2021.

The aim of this bibliometric analysis was to analyze the scientific output on adolescent social anxiety and its relationship with 15 psychoeducational variables in peer-reviewed journals during the period 2002-2021. The goal was to provide a comprehensive overview of the state of the art on adolescent social anxiety and academic/school achievement, performance, self-concept, self-esteem, self-efficacy, self-attributions, goals, attachment, adjustment, engagement, refusal, absenteeism, anxiety, learning strategies, and self-regulated learning. A search of scientific literature was conducted using Web of Science, and 157 empirical studies were identified. Analyses were conducted using bibliometrix 3.1 to avoid the risk of bias. The results suggested progressive growth in the scientific output on this research topic mainly in the USA, China, Spain, and Canada, and revealed trending issues and scientific interest regarding the relationship between adolescent social anxiety and academic/school achievement and performance. Other variables, such as academic/school attachment and self-regulated learning did not emerge. The results provide implications for practitioners (i.e., educators, clinical and educational psychologists, and psychiatrists), supporting emerging lines of research. Limitations include a lack of a review protocol and a lack of comparison with other international databases, such as PsychInfo, Scopus, PubMed, or ERIC.

Functionalized heteroatom-doped carbon dots for biomedical applications: A review.

Carbon nanoparticles (CDs) have recently drawn a great attention in (bio)chemical analysis, sensing and bioimaging owing to their photostability, water stability, minimal toxicity, biocompatibility and ease of surface functionalization. While the vast majority of CDs applications rely on exploiting their fluorescent properties, doping such nanomaterials with various elements has recently received increasing attention as an effective approach to modify their optoelectronic characteristics, introducing novel improved optical features such as phosphorescence, upconversion luminescence or multimodal imaging capabilities. This review article focuses in the recent advances on the synthesis of heteroatom-doped CDs, exhibiting distinctive features of high value for sensing and imaging, as well as various functionalization schemes developed for guided analyte labeling. Relevant applications in chemical sensing, bioimaging and disease therapy are here presented. A final section intends to provide an overview towards future developments of such emerging light-emitting nanomaterials in the design of future devices and strategies for (bio)analytical chemistry.

Extensible benchmarking of methods that identify and quantify polyadenylation sites from RNA-seq data.

The tremendous rate with which data is generated and analysis methods emerge makes it increasingly difficult to keep track of their domain of applicability, assumptions, limitations, and consequently, of the efficacy and precision with which they solve specific tasks. Therefore, there is an increasing need for benchmarks, and for the provision of infrastructure for continuous method evaluation. APAeval is an international community effort, organized by the RNA Society in 2021, to benchmark tools for the identification and quantification of the usage of alternative polyadenylation (APA) sites from short-read, bulk RNA-sequencing (RNA-seq) data. Here, we reviewed 17 tools and benchmarked eight on their ability to perform APA identification and quantification, using a comprehensive set of RNA-seq experiments comprising real, synthetic, and matched 3'-end sequencing data. To support continuous benchmarking, we have incorporated the results into the OpenEBench online platform, which allows for continuous extension of the set of methods, metrics, and challenges. We envisage that our analyses will assist researchers in selecting the appropriate tools for their studies, while the containers and reproducible workflows could easily be deployed and extended to evaluate new methods or data sets.

DEBBIE: The Open Access Database of Experimental Scaffolds and Biomaterials Built Using an Automated Text Mining Pipeline.

Biomaterials research output has experienced an exponential increase over the last three decades. The majority of research is published in the form of scientific articles and is therefore available as unstructured text, making it a challenging input for computational processing. Computational tools are becoming essential to overcome this information overload. Among them, text mining systems present an attractive option for the automated extraction of information from text documents into structured datasets. This work presents the first automated system for biomaterial related information extraction from the National Library of Medicine's premier bibliographic database (MEDLINE) research abstracts into a searchable database. The system is a text mining pipeline that periodically retrieves abstracts from PubMed and identifies research and clinical studies of biomaterials. Thereafter, the pipeline identifies sixteen concept types of interest in the abstract using the Biomaterials Annotator, a tool for biomaterials Named Entity Recognition (NER). These concepts of interest, along with the abstract and relevant metadata are then deposited in DEBBIE, the Database of Experimental Biomaterials and their Biological Effect. DEBBIE is accessible through a web application that provides keyword searches and displays results in an intuitive and meaningful manner, aiming to facilitate an efficient mapping and organization of biomaterials information.

Extensible benchmarking of methods that identify and quantify polyadenylation sites from RNA-seq data.

The tremendous rate with which data is generated and analysis methods emerge makes it increasingly difficult to keep track of their domain of applicability, assumptions, and limitations and consequently, of the efficacy and precision with which they solve specific tasks. Therefore, there is an increasing need for benchmarks, and for the provision of infrastructure for continuous method evaluation. APAeval is an international community effort, organized by the RNA Society in 2021, to benchmark tools for the identification and quantification of the usage of alternative polyadenylation (APA) sites from short-read, bulk RNA-sequencing (RNA-seq) data. Here, we reviewed 17 tools and benchmarked eight on their ability to perform APA identification and quantification, using a comprehensive set of RNA-seq experiments comprising real, synthetic, and matched 3'-end sequencing data. To support continuous benchmarking, we have incorporated the results into the OpenEBench online platform, which allows for seamless extension of the set of methods, metrics, and challenges. We envisage that our analyses will assist researchers in selecting the appropriate tools for their studies. Furthermore, the containers and reproducible workflows generated in the course of this project can be seamlessly deployed and extended in the future to evaluate new methods or datasets.

Relative and Transport Efficiency-Independent Approach for the Determination of Nanoparticle Size Using Single-Particle ICP-MS.

Herein, we introduce the first relative single-particle inductively coupled plasma mass spectrometry (spICP-MS) approach where size calibration is carried out using the target NP itself measured under different instrumental conditions without external dependence on the complex and prone-to-error determination of transport efficiency or mass flux calibrations, in contrast to most spICP-MS approaches. The simple approach proposed allows determining gold nanoparticle (AuNP) sizes, with errors ranging from 0.3 to 3.1% (corroborated by HR-TEM). It has been demonstrated that the changes observed in the single-particle histograms obtained for a suspension of AuNPs under different sensitivity conditions (n = 5) are directly and exclusively related to the mass (size) of the target AuNP itself. Interestingly, the relative nature of the approach shows that once the ICP-MS system has been calibrated with a generic NP standard, it is no longer necessary to repeat the calibration for the size determination of different unimetallic NPs carried out along time (at least 8 months), independently of their size (16-73 nm) and even nature (AuNP or AgNP). Additionally, neither the NP surface functionalization with biomolecules nor protein corona formation led to significant changes (relative errors slightly increased 1.3- to 1.5-fold, up to 7%) in the NP size determination, in contrast to conventional spICP-MS approaches where relative errors increased 2- to 8-fold, up to 32%. This feature could be especially valuable for the analysis of NPs in real samples without the need of matrix-matched calibration.