The Multicentre Acute ischemic stroke imaGIng and Clinical data (MAGIC) repository: rationale and blueprint.

Purpose: The Multicentre Acute ischemic stroke imaGIng and Clinical data (MAGIC) repository is a collaboration established in 2024 by seven stroke centres in Europe. MAGIC consolidates clinical and radiological data from acute ischemic stroke (AIS) patients who underwent endovascular therapy, intravenous thrombolysis, a combination of both, or conservative management.

Participants: All centres ensure accuracy and completeness of the data.

Combining in vitro, in vivo, and in silico approaches to evaluate the effect of serotonergic-based topical therapies on mild to moderate psoriasis.

Psoriasis, a chronic inflammatory skin disease, poses a significant burden on patients' quality of life and healthcare systems. While mild-to-moderate cases are treated topically, usually combined with phototherapy, severe cases require systemic treatment with immunosuppressants, retinoids or biologics. However, all available treatments have drawbacks in terms of efficiency and side effects.

CoREST Complex Inhibition Alters RNA Splicing to Promote Neoantigen Expression and Enhance Tumor Immunity.

Unlabelled: Epigenetic complexes tightly regulate gene expression and colocalize with RNA splicing machinery; however, the consequences of these interactions are uncertain. Here, we identify unique interactions of the CoREST repressor complex with RNA splicing factors and their functional consequences in tumorigenesis. Using mass spectrometry, in vivo binding assays, and cryo-EM we find that CoREST complex-splicing factor interactions are direct and perturbed by the CoREST complex inhibitor, corin, leading to extensive changes in RNA splicing in melanoma and other malignancies.

Upgrading skin barrier Protection: Addition of active ingredients to a Gelatin/Tannic Acid-Based hydrogel patch for treating skin lesions related to Personal protective Equipment.

Prolonged use of Personal Protective Equipment, like surgical masks, can cause skin issues such as acne ("maskne") and rosacea flare-ups due to pressure and moisture. While dressings can protect the skin, they often reduce mask effectiveness and lack pharmaceuticals to treat common skin lesions. This study introduces an innovative dual-function gelatin/tannic acid-based hydrogel patch incorporating metronidazole (1% w/w) or salicylic acid (2% w/w) to offer both skin protection and treatment.

Open-source electrophilic fragment screening platform to identify chemical starting points for UCHL1 covalent inhibitors.

Target-based screening of covalent fragment libraries with mass spectrometry has emerged as a powerful strategy to identify chemical starting points for small molecule inhibitors or find new binding pockets on proteins of interest. These libraries span diverse chemical space with a modest number of compounds. Screening covalent fragments against purified protein targets reduces the demands on the mass spectrometer with respect to absolute throughput, detection limit, and dynamic range.

Exploring the potential of 7,4'-di(diethylamino)flavylium as a novel photosensitizer for topical photodynamic therapy of skin cancer.

Photodynamic therapy (PDT) is a minimally invasive therapeutic approach that has shown promising results in recent years, particularly in the dermatological clinical treatment of several pathologies, including neoplastic skin diseases. In light of the recent discovery of the photosensitizing properties of a water-soluble group of amino-based flavylium dyes, research efforts have led to the development of a novel synthetic dye with two diethylamino moieties in its structure, 7,4'-di(diethylamino)flavylium (7,4'diN(Et)). This dye was tested as a potential photosensitizer for PDT of skin cancer.

Missing appointments in Parkinson´s Disease: A longitudinal study on the pattern of attendance and its effects on motor and non-motor symptoms, quality of life and disability progression.

Background And Purpose: Parkinson's Disease (PD) requires regular therapeutic adjustments and ongoing outpatient clinic follow-up. Nevertheless, the impact of appointment non-attendance on PD patients concerning the different symptomatic dimensions of the condition remains uncertain. We compared the level of attendance of PD and Essential Tremor (ET) patients and assessed the value of attendance variables as predictors of progression in cognition, motor dysfunction, affect, disability and health-related quality of life in PD.

Endovascular therapy in patients with acute intracranial non-terminal internal carotid artery occlusion (ICA-I).

Background: Acute intracranial occlusion of the internal carotid artery (ICA) can be distinguished into (a) occlusion of the terminal ICA, involving the proximal segments of the middle or anterior cerebral artery (ICA-L/-T) and (b) non-terminal intracranial occlusions of the ICA with patent circle of Willis (ICA-I). While patients with ICA-L/-T occlusion were included in all randomized controlled trials on endovascular therapy (EVT) in anterior large vessel occlusion, data on EVT in ICA-I occlusion is scarce. We thus aimed to evaluate effectiveness and safety of EVT in ICA-I occlusions in comparison to ICA-L/-T occlusions.

Leveraging HILIC/ERLIC Separations for Online Nanoscale LC-MS/MS Analysis of Phosphopeptide Isoforms from RNA Polymerase II C-terminal Domain.

The eukaryotic RNA polymerase II (Pol II) multi-protein complex transcribes mRNA and coordinates several steps of co-transcriptional mRNA processing and chromatin modification. The largest Pol II subunit, Rpb1, has a C-terminal domain (CTD) comprising dozens of repeated heptad sequences (Tyr1-Ser2-Pro3-Thr4-Ser5-Pro6-Ser7), each containing five phospho-accepting amino acids. The CTD heptads are dynamically phosphorylated, creating specific patterns correlated with steps of transcription initiation, elongation, and termination.

APIR: Aggregating Universal Proteomics Database Search Algorithms for Peptide Identification with FDR Control.

Advances in mass spectrometry (MS) have enabled high-throughput analysis of proteomes in biological systems. The state-of-the-art MS data analysis relies on database search algorithms to quantify proteins by identifying peptide-spectrum matches (PSMs), which convert mass spectra to peptide sequences. Different database search algorithms use distinct search strategies and thus may identify unique PSMs.

Identification of human circulating factors following remote ischemic conditioning (RIC): Potential impact on stroke.

Remote ischemic conditioning (RIC) is a procedure consisting of short cycles of ischemia applied in a limb that activates endogenous protection in distant organs, such as the brain. Despite the promising outcomes of RIC, the biochemical factors governing inter-organ communication remain largely unexplored, particularly in humans. A pilot study on 20 healthy humans was performed to identify potential circulating biochemical factors involved in RIC signalling.

Basilar artery occlusion management: An international survey of gender influence on management.

Background: The superiority of endovascular thrombectomy (EVT) over medical management was not established in two early basilar artery occlusion (BAO) randomized controlled trials. Despite this, many clinicians recommended EVT for acute BAO under certain circumstances. This paper aims to compare physicians' diagnostic and management strategies of BAO according to gender.

Template-assisted covalent modification underlies activity of covalent molecular glues.

Molecular glues are proximity-inducing small molecules that have emerged as an attractive therapeutic approach. However, developing molecular glues remains challenging, requiring innovative mechanistic strategies to stabilize neoprotein interfaces and expedite discovery. Here we unveil a trans-labeling covalent molecular glue mechanism, termed 'template-assisted covalent modification'.

Corrigendum: Tandem occlusions involving the internal carotid and anterior cerebral arteries-A rare form of stroke: results from the multicenter EVATRISP collaboration study.

[This corrects the article DOI: 10.3389/fneur.2022.

Molecular Bidents with Two Electrophilic Warheads as a New Pharmacological Modality.

A systematic strategy to develop dual-warhead inhibitors is introduced to circumvent the limitations of conventional covalent inhibitors such as vulnerability to mutations of the corresponding nucleophilic residue. Currently, all FDA-approved covalent small molecules feature one electrophile, leaving open a facile route to acquired resistance. We conducted a systematic analysis of human proteins in the protein data bank to reveal ∼400 unique targets amendable to dual covalent inhibitors, which we term "molecular bidents".

Endovascular Therapy in the Extended Time Window for Large Vessel Occlusion in Patients With Pre-Stroke Disability.

Background And Purpose: We compared the outcomes of endovascular therapy (EVT) in an extended time window in patients with large-vessel occlusion (LVO) between patients with and without pre-stroke disability.

Methods: In this prespecified analysis of the multinational CT for Late Endovascular Reperfusion study (66 participating sites, 10 countries between 2014 and 2022), we analyzed data from patients with acute ischemic stroke with a pre-stroke modified Rankin Scale (mRS) score of 0-4 and LVO who underwent EVT 6-24 hours from the time last seen well. The primary outcome was the composite of functional independence (FI; mRS score 0-2) or return to the pre-stroke mRS score (return of Rankin, RoR) at 90 days.

Safety and clinical outcomes of endovascular therapy versus medical management in late presentation of large ischemic stroke.

Introduction: The benefit of endovascular therapy (EVT) among stroke patients with large ischemic core (ASPECTS 0-5) in the extended time window outside of trial settings remains unclear. We analyzed the effect of EVT among these stroke patients in real-world settings.

Patients And Methods: The CT for Late Endovascular Reperfusion (CLEAR) study recruited patients from 66 centers in 10 countries between 01/2014 and 05/2022.