LifeTime and improving European healthcare through cell-based interceptive medicine.

Here we describe the LifeTime Initiative, which aims to track, understand and target human cells during the onset and progression of complex diseases, and to analyse their response to therapy at single-cell resolution. This mission will be implemented through the development, integration and application of single-cell multi-omics and imaging, artificial intelligence and patient-derived experimental disease models during the progression from health to disease. The analysis of large molecular and clinical datasets will identify molecular mechanisms, create predictive computational models of disease progression, and reveal new drug targets and therapies. The timely detection and interception of disease embedded in an ethical and patient-centred vision will be achieved through interactions across academia, hospitals, patient associations, health data management systems and industry. The application of this strategy to key medical challenges in cancer, neurological and neuropsychiatric disorders, and infectious, chronic inflammatory and cardiovascular diseases at the single-cell level will usher in cell-based interceptive medicine in Europe over the next decade.

The 2024 Nucleic Acids Research database issue and the online molecular biology database collection.

The 2024 Nucleic Acids Research database issue contains 180 papers from across biology and neighbouring disciplines. There are 90 papers reporting on new databases and 83 updates from resources previously published in the Issue. Updates from databases most recently published elsewhere account for a further seven. Nucleic acid databases include the new NAKB for structural information and updates from Genbank, ENA, GEO, Tarbase and JASPAR. The Issue's Breakthrough Article concerns NMPFamsDB for novel prokaryotic protein families and the AlphaFold Protein Structure Database has an important update. Metabolism is covered by updates from Reactome, Wikipathways and Metabolights. Microbes are covered by RefSeq, UNITE, SPIRE and P10K; viruses by ViralZone and PhageScope. Medically-oriented databases include the familiar COSMIC, Drugbank and TTD. Genomics-related resources include Ensembl, UCSC Genome Browser and Monarch. New arrivals cover plant imaging (OPIA and PlantPAD) and crop plants (SoyMD, TCOD and CropGS-Hub). The entire Database Issue is freely available online on the Nucleic Acids Research website (https://academic.oup.com/nar). Over the last year the NAR online Molecular Biology Database Collection has been updated, reviewing 1060 entries, adding 97 new resources and eliminating 388 discontinued URLs bringing the current total to 1959 databases. It is available at http://www.oxfordjournals.org/nar/database/c/.

The 2023 Nucleic Acids Research Database Issue and the online molecular biology database collection.

The 2023 Nucleic Acids Research Database Issue contains 178 papers ranging across biology and related fields. There are 90 papers reporting on new databases and 82 updates from resources previously published in the Issue. Six more papers are updates from databases most recently published elsewhere. Major nucleic acid databases reporting updates include Genbank, ENA, ChIPBase, JASPAR, mirDIP and the Issue's first Breakthrough Article, NACDDB for Circular Dichroism data. Updates from BMRB and RCSB cover experimental protein structural data while AlphaFold 2 computational structure predictions feature widely. STRING and REBASE are stand-out updates in the signalling and enzymes section. Immunology-related databases include CEDAR, the second Breakthrough Article, for cancer epitopes and receptors alongside returning IPD-IMGT/HLA and the new PGG.MHC. Genomics-related resources include Ensembl, GWAS Central and UCSC Genome Browser. Major returning databases for drugs and their targets include Open Targets, DrugCentral, CTD and Pubchem. The EMPIAR image archive appears in the Issue for the first time. The entire database Issue is freely available online on the Nucleic Acids Research website (https://academic.oup.com/nar). The NAR online Molecular Biology Database Collection has been updated, revisiting 463 entries, adding 92 new resources and eliminating 96 discontinued URLs so bringing the current total to 1764 databases. It is available at http://www.oxfordjournals.org/nar/database/c/.

The 2022 Nucleic Acids Research database issue and the online molecular biology database collection.

The 2022 Nucleic Acids Research Database Issue contains 185 papers, including 87 papers reporting on new databases and 85 updates from resources previously published in the Issue. Thirteen additional manuscripts provide updates on databases most recently published elsewhere. Seven new databases focus specifically on COVID-19 and SARS-CoV-2, including SCoV2-MD, the first of the Issue's Breakthrough Articles. Major nucleic acid databases reporting updates include MODOMICS, JASPAR and miRTarBase. The AlphaFold Protein Structure Database, described in the second Breakthrough Article, is the stand-out in the protein section, where the Human Proteoform Atlas and GproteinDb are other notable new arrivals. Updates from DisProt, FuzDB and ELM comprehensively cover disordered proteins. Under the metabolism and signalling section Reactome, ConsensusPathDB, HMDB and CAZy are major returning resources. In microbial and viral genomes taxonomy and systematics are well covered by LPSN, TYGS and GTDB. Genomics resources include Ensembl, Ensembl Genomes and UCSC Genome Browser. Major returning pharmacology resource names include the IUPHAR/BPS guide and the Therapeutic Target Database. New plant databases include PlantGSAD for gene lists and qPTMplants for post-translational modifications. The entire Database Issue is freely available online on the Nucleic Acids Research website (https://academic.oup.com/nar). Our latest update to the NAR online Molecular Biology Database Collection brings the total number of entries to 1645. Following last year's major cleanup, we have updated 317 entries, listing 89 new resources and trimming 80 discontinued URLs. The current release is available at http://www.oxfordjournals.org/nar/database/c/.

The 2021 Nucleic Acids Research database issue and the online molecular biology database collection.

The 2021 Nucleic Acids Research database Issue contains 189 papers spanning a wide range of biological fields and investigation. It includes 89 papers reporting on new databases and 90 covering recent changes to resources previously published in the Issue. A further ten are updates on databases most recently published elsewhere. Seven new databases focus on COVID-19 and SARS-CoV-2 and many others offer resources for studying the virus. Major returning nucleic acid databases include NONCODE, Rfam and RNAcentral. Protein family and domain databases include COG, Pfam, SMART and Panther. Protein structures are covered by RCSB PDB and dispersed proteins by PED and MobiDB. In metabolism and signalling, STRING, KEGG and WikiPathways are featured, along with returning KLIFS and new DKK and KinaseMD, all focused on kinases. IMG/M and IMG/VR update in the microbial and viral genome resources section, while human and model organism genomics resources include Flybase, Ensembl and UCSC Genome Browser. Cancer studies are covered by updates from canSAR and PINA, as well as newcomers CNCdatabase and Oncovar for cancer drivers. Plant comparative genomics is catered for by updates from Gramene and GreenPhylDB. The entire Database Issue is freely available online on the Nucleic Acids Research website (https://academic.oup.com/nar). The NAR online Molecular Biology Database Collection has been substantially updated, revisiting nearly 1000 entries, adding 90 new resources and eliminating 86 obsolete databases, bringing the current total to 1641 databases. It is available at https://www.oxfordjournals.org/nar/database/c/.

The 27th annual Nucleic Acids Research database issue and molecular biology database collection.

The 2020 Nucleic Acids Research Database Issue contains 148 papers spanning molecular biology. They include 59 papers reporting on new databases and 79 covering recent changes to resources previously published in the issue. A further ten papers are updates on databases most recently published elsewhere. This issue contains three breakthrough articles: AntiBodies Chemically Defined (ABCD) curates antibody sequences and their cognate antigens; SCOP returns with a new schema and breaks away from a purely hierarchical structure; while the new Alliance of Genome Resources brings together a number of Model Organism databases to pool knowledge and tools. Major returning nucleic acid databases include miRDB and miRTarBase. Databases for protein sequence analysis include CDD, DisProt and ELM, alongside no fewer than four newcomers covering proteins involved in liquid-liquid phase separation. In metabolism and signaling, Pathway Commons, Reactome and Metabolights all contribute papers. PATRIC and MicroScope update in microbial genomes while human and model organism genomics resources include Ensembl, Ensembl genomes and UCSC Genome Browser. Immune-related proteins are covered by updates from IPD-IMGT/HLA and AFND, as well as newcomers VDJbase and OGRDB. Drug design is catered for by updates from the IUPHAR/BPS Guide to Pharmacology and the Therapeutic Target Database. The entire Database Issue is freely available online on the Nucleic Acids Research website (https://academic.oup.com/nar). The NAR online Molecular Biology Database Collection has been revised, updating 305 entries, adding 65 new resources and eliminating 125 discontinued URLs; so bringing the current total to 1637 databases. It is available at http://www.oxfordjournals.org/nar/database/c/.

The 26th annual Nucleic Acids Research database issue and Molecular Biology Database Collection.

The 2019 Nucleic Acids Research (NAR) Database Issue contains 168 papers spanning molecular biology. Among them, 64 are new and another 92 are updates describing resources that appeared in the Issue previously. The remaining 12 are updates on databases most recently published elsewhere. This Issue contains two Breakthrough articles, on the Virtual Metabolic Human (VMH) database which links human and gut microbiota metabolism with diet and disease, and Vibrism DB, a database of mouse brain anatomy and gene (co-)expression with sophisticated visualization and session sharing. Major returning nucleic acid databases include RNAcentral, miRBase and LncRNA2Target. Protein sequence databases include UniProtKB, InterPro and Pfam, while wwPDB and RCSB cover protein structure. STRING and KEGG update in the section on metabolism and pathways. Microbial genomes are covered by IMG/M and resources for human and model organism genomics include Ensembl, UCSC Genome Browser, GENCODE and Flybase. Genomic variation and disease are well-covered by GWAS Catalog, PopHumanScan, OMIM and COSMIC, CADD being another major newcomer. Major new proteomics resources reporting here include iProX and jPOSTdb. The entire database issue is freely available online on the NAR website (https://academic.oup.com/nar). The NAR online Molecular Biology Database Collection has been updated, reviewing 506 entries, adding 66 new resources and eliminating 147 discontinued URLs, bringing the current total to 1613 databases. It is available at http://www.oxfordjournals.org/nar/database/c.

The 2018 Nucleic Acids Research database issue and the online molecular biology database collection.

The 2018 Nucleic Acids Research Database Issue contains 181 papers spanning molecular biology. Among them, 82 are new and 84 are updates describing resources that appeared in the Issue previously. The remaining 15 cover databases most recently published elsewhere. Databases in the area of nucleic acids include 3DIV for visualisation of data on genome 3D structure and RNArchitecture, a hierarchical classification of RNA families. Protein databases include the established SMART, ELM and MEROPS while GPCRdb and the newcomer STCRDab cover families of biomedical interest. In the area of metabolism, HMDB and Reactome both report new features while PULDB appears in NAR for the first time. This issue also contains reports on genomics resources including Ensembl, the UCSC Genome Browser and ENCODE. Update papers from the IUPHAR/BPS Guide to Pharmacology and DrugBank are highlights of the drug and drug target section while a number of proteomics databases including proteomicsDB are also covered. The entire Database Issue is freely available online on the Nucleic Acids Research website (https://academic.oup.com/nar). The NAR online Molecular Biology Database Collection has been updated, reviewing 138 entries, adding 88 new resources and eliminating 47 discontinued URLs, bringing the current total to 1737 databases. It is available at http://www.oxfordjournals.org/nar/database/c/.

Multimodal Prediction of Five-Year Breast Cancer Recurrence in Women Who Receive Neoadjuvant Chemotherapy.

In current clinical practice, it is difficult to predict whether a patient receiving neoadjuvant chemotherapy (NAC) for breast cancer is likely to encounter recurrence after treatment and have the cancer recur locally in the breast or in other areas of the body. We explore the use of clinical history, immunohistochemical markers, and multiparametric magnetic resonance imaging (DCE, ADC, Dixon) to predict the risk of post-treatment recurrence within five years. We performed a retrospective study on a cohort of 1738 patients from Institut Curie and analyzed the data using classical machine learning, image processing, and deep learning. Our results demonstrate the ability to predict recurrence prior to NAC treatment initiation using each modality alone, and the possible improvement achieved by combining the modalities. When evaluated on holdout data, the multimodal model achieved an AUC of 0.75 (CI: 0.70, 0.80) and 0.57 specificity at 0.90 sensitivity. We then stratified the data based on known prognostic biomarkers. We found that our models can provide accurate recurrence predictions (AUC > 0.89) for specific groups of women under 50 years old with poor prognoses. A version of our method won second place at the BMMR2 Challenge, with a very small margin from being first, and was a standout from the other challenge entries.

Untangling Data in Precision Oncology - A Model for Chronic Diseases?

OBJECTIVES: Any attempt to introduce new data types in the entangled hospital infrastructure should help to unravel old knots without tangling new ones. Health data from a wide range of sources has become increasingly available. We witness an insatiable thirst for data in oncology as treatment paradigms are shifting to targeted molecular therapies. METHODS: From nineteenth-century medical notes consisting entirely of narrative description to standardised forms recording physical examination and medical notes, we have nowadays moved to electronic health records (EHRs). All our analogue medical records are rendered as sequences of zeros and ones changing how we capture and share data. The challenge we face is to offload the analysis without entrusting a machine (or algorithms) to make major decisions about a diagnosis, a treatment, or a surgery, keeping the human oversight. Computers don't have judgment, they lack context. RESULTS: EHRs have become the latest addition to our toolset to look after patients. Moore's law and general advances in computation have contributed to make EHRs a cornerstone of Molecular Tumour Boards, presenting a detailed and unique description of a tumour and treatment options. CONCLUSIONS: Precision oncology, as a systematic approach matching the most accurate and effective treatment to each individual cancer patient, based on a molecular profile, is already expanding to other disease areas.

Gender-Bashing in Adolescents: Structural Relations with Heterosexual Matrix, Racism/Xenophobia and Attitudes Toward Bullying.

BACKGROUND: This study examined the combined influence of gender variables (specifically gender stereotypes, sexism, and genderism/transphobia) as well as racism/xenophobia and attitudes toward bullying roles on gender-bashing. METHODS: A trans-cultural sample of 2410 Spanish and Portuguese students participated in the study (mean age = 15.13). Structural equation modeling and multiple group analyses were used to examine the relationships among variables. RESULTS: The model revealed a good fit with the data for the whole sample. Results showed that instrumentality, hostile sexism, genderism/transphobia, racism/xenophobia, and positive attitudes toward the bully were positively correlated with gender-bashing. An inverse pattern was also observed: expressiveness, benevolent sexism, and positive attitudes toward the defender were negatively correlated with gender-bashing. Overall, the eight variables explained 48% of the variance of gender-bashing. Structural relationships among the assessed constructs were equivalent for girls and boys, and for Spain and Portugal. CONCLUSIONS: These results reveal the need to implement inclusive educational policies to improve school health, which promote expressiveness, egalitarian attitudes, and sexual and cultural diversity.