FRINK Linked Data Fragments server

Matches in SemOpenAlex for { <https://semopenalex.org/work/W4381620051> ?p ?o ?g. }

• W4381620051 abstract "Abstract Study question Is there a most represented group of approved drugs that can revert the impaired endometrial expression pattern associated with endometrial failure to improve reproductive outcomes? Summary answer Transcriptomics-based drug repurposing strategy identifies drugs currently used for nervous system diseases as repurposing candidates for endometrial therapies in infertility. What is known already Endometrium is a dynamic tissue with a key role in human reproduction whose alterations lead to infertility problems. Transcriptomic studies have been performed to understand molecular bases of endometrial failure, but effective treatments remain unknown. Transcriptomics-based drug repurposing strategy identifies approved drugs with a reversed disease gene expression profile, where genes up-regulated in a condition are down-regulated with the drug therapy and vice-versa, having a predicted therapeutic effect. Encouraging results for conditions such as preterm birth or cancer have already been shown using this methodology. In this study, we applied this approach to obtain treatment predictions for endometrial failure. Study design, size, duration A prospective multicenter study was performed between January 2019 and December 2021. A total of 192 women (18-50 years old) undergoing IVF with good-quality embryos were included and an endometrial sample in mid-secretory phase was collected to study their gene expression. Through artificial intelligence algorithms, we identified transcriptomic patterns with different endometrial prognoses. Expression changes among good or poor prognosis profiles were used to identify potential approved therapies to treat infertility leveraging drug expression databases. Participants/materials, setting, methods Gene signatures associated with poor prognosis were identified (FDR&lt;0.05) and queried against the Connectivity Map database, containing gene expression profiles for 1,309 drugs in 5 different cell lines. Statistical analyses were performed to evaluate the drugs selected and obtain a score based on the drug expression reversal of the disease signatures. Significant drugs (adj. p-value) inversely associated with the gene signatures were highlighted. Finally, approved drugs were classified according to Anatomical Therapeutic Chemical codes. Main results and the role of chance We identified four transcriptomic profiles significantly (p-value&lt;0.05) associated with different reproductive outcomes in the first embryo transfer after biopsy collection. Two poor prognosis profiles, one of them more related to clinical miscarriage, P1 (implantation rate = 30.4%, live birth rate = 42.9%, clinical miscarriage rate = 50%), and another to biochemical miscarriage, P2 (implantation rate = 20.0%, live birth rate = 33.3%, biochemical miscarriage rate = 66.7%) were compared with the best prognosis profile (implantation rate = 64.6%, live birth rate = 95.2%, biochemical miscarriage rate = 0.0%, clinical miscarriage rate = 4.8%), obtaining a total of 439 and 4,984 differential expressed genes, respectively for P1 and P2. After applying the drug repurposing methodology, we selected 50 and 32 significant approved drugs (adj. p-value&lt;0.05) for P1 and P2. A total of 14 and 11 different drugs categories were obtained for each poor prognosis profile highlighting Nervous System (26%) and Alimentary tract and metabolism (12%) for P1, and Nervous System (23%), Antineoplastic and Immune modulating agents (15%) and Antiparasitic products (15%) for P2. Moreover, when both nervous system categories were compared, a total of 15 drugs were found in common, making possible the use of a unique drug for both profiles. Limitations, reasons for caution Since the Connectivity Map database does not include endometrial tissue, the action of these drugs should be validated experimentally in endometrial cell culture. Afterwards, to prioritize the best drug, side effects and approved doses reported in drug databases should be taken into consideration in further analyses. Wider implications of the findings The use of drug repurposing generates hypotheses for finding suitable drugs for endometrial failure, not requiring preclinical trials and going directly to Phase II clinical trials. These potential treatments will improve reproductive outcomes. Nervous system drugs seem to have a considerable effect on endometrium revealing possible causes of endometrial failure. Trial registration number Not Applicable" @default.
• W4381620051 created "2023-06-23" @default.
• W4381620051 creator A5007163271 @default.
• W4381620051 creator A5010192662 @default.
• W4381620051 creator A5019980125 @default.
• W4381620051 creator A5039941652 @default.
• W4381620051 creator A5047452696 @default.
• W4381620051 creator A5049148540 @default.
• W4381620051 creator A5053763570 @default.
• W4381620051 creator A5079179603 @default.
• W4381620051 creator A5086033147 @default.
• W4381620051 date "2023-06-01" @default.
• W4381620051 modified "2023-10-16" @default.
• W4381620051 title "P-335 Nervous system drugs are predicted as potential repurposing candidates for treatment in endometrial failure" @default.
• W4381620051 doi "https://doi.org/10.1093/humrep/dead093.693" @default.
• W4381620051 hasPublicationYear "2023" @default.
• W4381620051 type Work @default.
• W4381620051 citedByCount "0" @default.
• W4381620051 crossrefType "journal-article" @default.
• W4381620051 hasAuthorship W4381620051A5007163271 @default.
• W4381620051 hasAuthorship W4381620051A5010192662 @default.
• W4381620051 hasAuthorship W4381620051A5019980125 @default.
• W4381620051 hasAuthorship W4381620051A5039941652 @default.
• W4381620051 hasAuthorship W4381620051A5047452696 @default.
• W4381620051 hasAuthorship W4381620051A5049148540 @default.
• W4381620051 hasAuthorship W4381620051A5053763570 @default.
• W4381620051 hasAuthorship W4381620051A5079179603 @default.
• W4381620051 hasAuthorship W4381620051A5086033147 @default.
• W4381620051 hasBestOaLocation W43816200511 @default.
• W4381620051 hasConcept C103637391 @default.
• W4381620051 hasConcept C104317684 @default.
• W4381620051 hasConcept C121608353 @default.
• W4381620051 hasConcept C126322002 @default.
• W4381620051 hasConcept C143998085 @default.
• W4381620051 hasConcept C150194340 @default.
• W4381620051 hasConcept C162317418 @default.
• W4381620051 hasConcept C18903297 @default.
• W4381620051 hasConcept C2777088508 @default.
• W4381620051 hasConcept C2777688143 @default.
• W4381620051 hasConcept C2779134260 @default.
• W4381620051 hasConcept C2779234561 @default.
• W4381620051 hasConcept C2780035454 @default.
• W4381620051 hasConcept C519536355 @default.
• W4381620051 hasConcept C54355233 @default.
• W4381620051 hasConcept C60644358 @default.
• W4381620051 hasConcept C71924100 @default.
• W4381620051 hasConcept C86803240 @default.
• W4381620051 hasConcept C98274493 @default.
• W4381620051 hasConceptScore W4381620051C103637391 @default.
• W4381620051 hasConceptScore W4381620051C104317684 @default.
• W4381620051 hasConceptScore W4381620051C121608353 @default.
• W4381620051 hasConceptScore W4381620051C126322002 @default.
• W4381620051 hasConceptScore W4381620051C143998085 @default.
• W4381620051 hasConceptScore W4381620051C150194340 @default.
• W4381620051 hasConceptScore W4381620051C162317418 @default.
• W4381620051 hasConceptScore W4381620051C18903297 @default.
• W4381620051 hasConceptScore W4381620051C2777088508 @default.
• W4381620051 hasConceptScore W4381620051C2777688143 @default.
• W4381620051 hasConceptScore W4381620051C2779134260 @default.
• W4381620051 hasConceptScore W4381620051C2779234561 @default.
• W4381620051 hasConceptScore W4381620051C2780035454 @default.
• W4381620051 hasConceptScore W4381620051C519536355 @default.
• W4381620051 hasConceptScore W4381620051C54355233 @default.
• W4381620051 hasConceptScore W4381620051C60644358 @default.
• W4381620051 hasConceptScore W4381620051C71924100 @default.
• W4381620051 hasConceptScore W4381620051C86803240 @default.
• W4381620051 hasConceptScore W4381620051C98274493 @default.
• W4381620051 hasIssue "Supplement_1" @default.
• W4381620051 hasLocation W43816200511 @default.
• W4381620051 hasOpenAccess W4381620051 @default.
• W4381620051 hasPrimaryLocation W43816200511 @default.
• W4381620051 hasRelatedWork W3050951227 @default.
• W4381620051 hasRelatedWork W3137715854 @default.
• W4381620051 hasRelatedWork W3159848998 @default.
• W4381620051 hasRelatedWork W4205275007 @default.
• W4381620051 hasRelatedWork W4224322440 @default.
• W4381620051 hasRelatedWork W4225380062 @default.
• W4381620051 hasRelatedWork W4283755545 @default.
• W4381620051 hasRelatedWork W4285179237 @default.
• W4381620051 hasRelatedWork W4307501484 @default.
• W4381620051 hasRelatedWork W3099438243 @default.
• W4381620051 hasVolume "38" @default.
• W4381620051 isParatext "false" @default.
• W4381620051 isRetracted "false" @default.
• W4381620051 workType "article" @default.