(A) Representative examples of raw mEPSCs recorded in mature (12–16 DIV) WT and PrP-null hippocampal neurons in culture

In PrP-null neurons, NMDA-mediated mEPSCs were observed to be larger and showed prolonged decay times. (B) Event histograms for mEPSC amplitude (top) and decay time (bottom). Note that mEPSCs in PrP-null neurons exhibit a shift toward larger amplitude events and increased decay time constants. (C) Cumulative probability plots for mEPSC amplitude and decay times showing a shift in each summed distribution toward larger events with longer decay times (P < 0.05; Kolmogorov-Smirnov test). (D) Mean values for mEPSC waveform parameters showing increased EPSC amplitudes and prolonged decay times. Here, decay time refers to the time required for an e-fold reduction in peak current amplitude. Data are represented as mean ± SEM (error bars), with statistical significance denoted as *, P < 0.05 and **, P < 0.001. Numbers in parentheses indicate the number of cells.<p><b>Copyright information:</b></p><p>Taken from "Prion protein attenuates excitotoxicity by inhibiting NMDA receptors"</p><p></p><p>The Journal of Cell Biology 2008;181(3):551-565.</p><p>Published online 5 May 2008</p><p>PMCID:PMC2364707.</p><p></p

(A) Fluoro-Jade labeling of neuronal bodies and processes in hippocampal sections in response to injection of vehicle (left) or NMDA (10-nmol equivalent; right)

(B) Quantification of lesion size relative to the hippocampus over a series of three to six sections per animal ( = 5 per experimental group). Data are represented as mean ± SEM (error bars), with statistical significance denoted as **, P < 0.001. Bar, 200 μm.<p><b>Copyright information:</b></p><p>Taken from "Prion protein attenuates excitotoxicity by inhibiting NMDA receptors"</p><p></p><p>The Journal of Cell Biology 2008;181(3):551-565.</p><p>Published online 5 May 2008</p><p>PMCID:PMC2364707.</p><p></p

(A) Western blot analysis of the NR2D subunit protein expression in neonatal and adult hippocampal tissue obtained from the WT and PrP-null mouse

α-Actin expression was used as a loading control. (B) NMDAR subunit surface expression as visualized by immunolabel reactivity with an antibody targeted against an extracellular (N terminus) epitope of NR2D. A punctate pattern of receptor distribution is visualized along dendritic processes. The depth of field is ∼1 μm. (C) Surface expression of NR2D relative to total cellular NR2D protein content as quantified using an ELISA assay in permeabilized (P) and nonpermeabilized (NP) cells. The number of neuronal culture samples is indicated in parentheses. Error bars represent SEM. (D) Coimmunoprecipitation of PrP and NR2D using both permutations of tag and probe showing that PrP and NR2D are in a complex. In the top panel, the blot was probed with a PrP antibody, and in the bottom panel, membrane was probed with NR2D antibody. The lane labeled control reflects beads without antibody. The experiment is a representative example of four different repetitions for both neonatal and adult mouse hippocampal tissue. (E) Western blot demonstrating the lack of coimmunoprecipitation between NR2B and PrP, whereas NR2B can be detected in brain homogenate (input). (F) Costaining of WT mouse hippocampal neurons for PrP (red) and NR2D (blue). The cells were not permeabilized, thus allowing for the selective staining of cell surface protein. The white line in the top left panel indicates the position of the linescan shown in the bottom left panel. The rectangle in the merged image (top right) corresponds to the magnified images shown at the bottom right. The arrowheads highlight examples of clear colocalization between NR2D and PrP. Bars: (B, top left) 7.5 μm; (B, top right and F, top) 10 μm; (B, bottom) 1 μm; (F, bottom) 2 μm.<p><b>Copyright information:</b></p><p>Taken from "Prion protein attenuates excitotoxicity by inhibiting NMDA receptors"</p><p></p><p>The Journal of Cell Biology 2008;181(3):551-565.</p><p>Published online 5 May 2008</p><p>PMCID:PMC2364707.</p><p></p

(A) Paired pulses evoked by stimulation of the Schaffer collaterals in slices from P30–45 mice in normal artificial cerebrospinal fluid (aCSF)

(B) Quantification of the number of population spikes in WT and PrP-null slices in aCSF. (C, top) Minimum stimulus intensity required to evoke a single population spike in WT and PrP-null slices. (middle) Stimulus intensity required to evoke maximum single population spike amplitude. (bottom) Extent of paired pulse facilitation in WT and PrP-null slices. (D, top) Field potentials recorded from PrP-null slices before and after the application of 50 μM APV as shown for P2. (bottom) Quantification of the number of population spikes before and after APV application in PrP-null slices. (E) Evoked field potentials recorded after 5 min of perfusion in zero-magnesium aCSF (ZM-aCSF). The gray arrows indicate successive population spikes, which are augmented in the PrP-null slices. (F, left) The number of population spikes overriding the fEPSP in slices exposed to ZM-aCSF. (second graph) Time to the observance of the first seizurelike discharge in ZM-aCSF. (third graph) Time to the occurrence of the first seizurelike event (SLE) upon perfusion with ZM-aCSF. (right) Duration of seizurelike events in WT and PrP-null slices. The black and gray arrowheads indicate the primary population spikes and the additional population spikes, respectively, overriding the fEPSP in each pulse (P1 and P2); these latter polyspikes were only observed in PrP-null mice. Data are represented as mean ± SEM (error bars) with statistical significance denoted as *, P < 0.05 and **, P < 0.001. Numbers in parentheses indicate the number of slices.<p><b>Copyright information:</b></p><p>Taken from "Prion protein attenuates excitotoxicity by inhibiting NMDA receptors"</p><p></p><p>The Journal of Cell Biology 2008;181(3):551-565.</p><p>Published online 5 May 2008</p><p>PMCID:PMC2364707.</p><p></p

(A) Light microscope images of neuronal cultures after 20 min of exposure to 0

3, 0.6, and 1.0 mM NMDA followed by 24-h recovery. Cells were stained with trypan blue (dark blue) and TUNEL (brown); methyl green was used as the counterstain. (B) Mean cell counts for trypan blue– and TUNEL-stained cells in WT and PrP-null cultures. (C) Light microscope images showing TUNEL-stained neurons from PrP-null mice in the presence of NMDA and NMDA + APV. (D) Percentage of TUNEL-positive neurons from PrP-null mice in response to NMDA and NMDA + APV. The drug concentrations were 1 mM NMDA and 100 μM APV. Data are represented as mean ± SEM (error bars), with statistical significance denoted as *, P < 0.05 and **, P < 0.001. Data were obtained from four culture rounds, and six random fields were imaged per condition. Bar, 100 μm.<p><b>Copyright information:</b></p><p>Taken from "Prion protein attenuates excitotoxicity by inhibiting NMDA receptors"</p><p></p><p>The Journal of Cell Biology 2008;181(3):551-565.</p><p>Published online 5 May 2008</p><p>PMCID:PMC2364707.</p><p></p

Data_Sheet_1_Machine-learning assisted swallowing assessment: a deep learning-based quality improvement tool to screen for post-stroke dysphagia.docx

IntroductionPost-stroke dysphagia is common and associated with significant morbidity and mortality, rendering bedside screening of significant clinical importance. Using voice as a biomarker coupled with deep learning has the potential to improve patient access to screening and mitigate the subjectivity associated with detecting voice change, a component of several validated screening protocols.MethodsIn this single-center study, we developed a proof-of-concept model for automated dysphagia screening and evaluated the performance of this model on training and testing cohorts. Patients were admitted to a comprehensive stroke center, where primary English speakers could follow commands without significant aphasia and participated on a rolling basis. The primary outcome was classification either as a pass or fail equivalent using a dysphagia screening test as a label. Voice data was recorded from patients who spoke a standardized set of vowels, words, and sentences from the National Institute of Health Stroke Scale. Seventy patients were recruited and 68 were included in the analysis, with 40 in training and 28 in testing cohorts, respectively. Speech from patients was segmented into 1,579 audio clips, from which 6,655 Mel-spectrogram images were computed and used as inputs for deep-learning models (DenseNet and ConvNext, separately and together). Clip-level and participant-level swallowing status predictions were obtained through a voting method.ResultsThe models demonstrated clip-level dysphagia screening sensitivity of 71% and specificity of 77% (F1 = 0.73, AUC = 0.80 [95% CI: 0.78–0.82]). At the participant level, the sensitivity and specificity were 89 and 79%, respectively (F1 = 0.81, AUC = 0.91 [95% CI: 0.77–1.05]).DiscussionThis study is the first to demonstrate the feasibility of applying deep learning to classify vocalizations to detect post-stroke dysphagia. Our findings suggest potential for enhancing dysphagia screening in clinical settings. https://github.com/UofTNeurology/masa-opensource</p

sj-pdf-2-wso-10.1177_17474930231205208 – Supplemental material for Safety and efficacy of tenecteplase versus alteplase in stroke patients with carotid tandem lesions: Results from the AcT trial

Supplemental material, sj-pdf-2-wso-10.1177_17474930231205208 for Safety and efficacy of tenecteplase versus alteplase in stroke patients with carotid tandem lesions: Results from the AcT trial by Fouzi Bala, Mohammed Almekhlafi, Nishita Singh, Ibrahim Alhabli, Ayoola Ademola, Shelagh B Coutts, Yan Deschaintre, Houman Khosravani, Ramana Appireddy, Francois Moreau, Stephen Phillips, Gord Gubitz, Aleksander Tkach, Luciana Catanese, Dar Dowlatshahi, George Medvedev, Jennifer Mandzia, Aleksandra Pikula, Jay Shankar, Heather Williams, Thalia S Field, Alejandro Manosalva, Muzaffar Siddiqui, Atif Zafar, Oje Imoukhoude, Gary Hunter, Faysal Benali, MacKenzie Horn, Michael D Hill, Michel Shamy, Tolulope T Sajobi, Brian H Buck, Richard H Swartz, Bijoy K Menon and Alexandre Y Poppe in International Journal of Stroke</p

sj-pdf-1-wso-10.1177_17474930231205208 – Supplemental material for Safety and efficacy of tenecteplase versus alteplase in stroke patients with carotid tandem lesions: Results from the AcT trial

Supplemental material, sj-pdf-1-wso-10.1177_17474930231205208 for Safety and efficacy of tenecteplase versus alteplase in stroke patients with carotid tandem lesions: Results from the AcT trial by Fouzi Bala, Mohammed Almekhlafi, Nishita Singh, Ibrahim Alhabli, Ayoola Ademola, Shelagh B Coutts, Yan Deschaintre, Houman Khosravani, Ramana Appireddy, Francois Moreau, Stephen Phillips, Gord Gubitz, Aleksander Tkach, Luciana Catanese, Dar Dowlatshahi, George Medvedev, Jennifer Mandzia, Aleksandra Pikula, Jay Shankar, Heather Williams, Thalia S Field, Alejandro Manosalva, Muzaffar Siddiqui, Atif Zafar, Oje Imoukhoude, Gary Hunter, Faysal Benali, MacKenzie Horn, Michael D Hill, Michel Shamy, Tolulope T Sajobi, Brian H Buck, Richard H Swartz, Bijoy K Menon and Alexandre Y Poppe in International Journal of Stroke</p