Centre Hospitalier Universitaire (CHU) de Québec-Université Laval

In the last two decades, numerous in silico methods have been developed for drug repurposing, to accelerate and reduce the risks about early drug development. Particularly, following Connectivity Map, dozens of distinct data-driven methods have been implemented to find candidates from the comparison of differential transcriptomic signatures. Interestingly, there have been multiple proposals to integrate available knowledge using systems biology databases and adapted algorithms from the network biology research field. Despite their similarities, these methods have been formulated inconsistently over the years, even if some of them are fundamentally similar. The aim of this review is to reconcile these integrative methods, focusing on elucidating their common structures while underlining the specificities of their strategies. To achieve this, we classified those methods into two main categories, provided schematic workflow representations, and presented a homogenized formulation for each.

Implantation is a complex process requiring a prepared, receptive endometrium, reliant on synchronized decidualization of stromal cells. During this process, cell proliferation and apoptosis are tightly regulated by signaling factors, including the survival and proliferation of the PI3K/AKT pathway. The three AKT isoforms each play distinct physiological roles, but their specific functions in endometrial cell survival and apoptosis remain unclear. We hypothesize that for successful implantation, each AKT isoform has distinct roles in the endometrium during decidualization, which varies throughout the process. To explore this, we developed a unique PGR-Cre tissue-specific mouse model with single and combined knockouts (KO) of each AKT isoform. Using artificial decidualization during pseudopregnancy and normal gestation, we investigated the specific activity of each AKT isoform and their downstream targets to assess the role of AKT pathway. Our results showed that the AKT1–2 KO genotype failed to decidualize during pseudopregnancy and exhibited a reduced number of implantation sites. Interestingly, AKT3 was hyperphosphorylated in the AKT1–2 KO mice and emerged as the primary isoform active throughout decidualization, specifically signaling through GSK3B. This study suggests distinct yet partially redundant roles for AKT1 and AKT2 during decidualization and embryo implantation. We propose that the AKT pathway plays significant role in fertility, and a deeper understanding of its involvement in decidualization could lead to improved strategies for addressing fertility issues. These findings highlight the importance of AKT activity in the cellular and molecular regulation of mouse fertility.

Aphasia is one of the most common and most debilitating after-effects of a stroke. In the acute phase of a stroke, referrals to speech-language pathology (SLP) are frequently guided by clinical impressions rather than validated tests.

This study aimed to evaluate the advantages of incorporating the Screening test for language disorders in adults and the elderly (DTLA) into clinical practice for detecting language disorders during the acute phase of stroke.

The study includes a retrospective and a prospective component, including a questionnaire on the acceptability, feasibility and usefulness of using the DTLA in patients in the acute phase of stroke.

Sixty-one patients admitted for stroke were recruited for each of the two components. The introduction of the DTLA in the prospective component of the study had a significant impact on the detection of language impairment, as more notes about language were found in patients' medical records and more referrals were made to SLP.

Using a screening test can improve the detection of aphasia during the acute phase of stroke, particularly in patients whose impairments might not be easily identified through subjective assessments.