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BACKGROUND: Stroke remains a major health concern globally, with oral anticoagulants widely prescribed for stroke prevention. The efficacy and safety of mechanical thrombectomy (MT) in anticoagulated patients with distal medium vessel occlusions (DMVO) are not well understood. METHODS: This retrospective analysis involved 1282 acute ischemic stroke (AIS) patients who underwent MT in 37 centers across North America, Asia, and Europe from September 2017 to July 2023. Data on demographics, clinical presentation, treatment specifics, and outcomes were collected. The primary outcomes were functional outcomes at 90 days post-MT, measured by modified Rankin Scale (mRS) scores. Secondary outcomes included reperfusion rates, mortality, and hemorrhagic complications. RESULTS: Of the patients, 223 (34%) were on anticoagulation therapy. Anticoagulated patients were older (median age 78 vs 74 years; p

BACKGROUND: Despite the proven effectiveness of endovascular therapy (EVT) in acute ischemic strokes (AIS) involving anterior circulation large vessel occlusions, isolated posterior cerebral artery (PCA) occlusions (iPCAo) remain underexplored in clinical trials. This study investigates the comparative effectiveness and safety of EVT against medical management (MM) in patients with iPCAo. METHODS: This multinational, multicenter propensity score-weighted study analyzed data from the Multicenter Analysis of primary Distal medium vessel occlusions: effect of Mechanical Thrombectomy (MAD-MT) registry, involving 37 centers across North America, Asia, and Europe. We included iPCAo patients treated with either EVT or MM. The primary outcome was the modified Rankin Scale (mRS) at 90 days, with secondary outcomes including functional independence, mortality, and safety profiles such as hemorrhagic complications. RESULTS: A total of 177 patients were analyzed (88 MM and 89 EVT). EVT showed a statistically significant improvement in 90-day mRS scores (OR = 0.55, 95% CI = 0.30-1.00, p = 0.048), functional independence (OR = 2.52, 95% CI = 1.02-6.20, p = 0.045), and a reduction in 90-day mortality (OR = 0.12, 95% CI = 0.03-0.54, p = 0.006) compared to MM. Hemorrhagic complications were not significantly different between the groups. CONCLUSION: EVT for iPCAo is associated with better neurological outcomes and lower mortality compared to MM, without an increased risk of hemorrhagic complications. Nevertheless, these results should be interpreted with caution due to the studys observational design. The findings are hypothesis-generating and highlight the need for future randomized controlled trials to confirm these observations and establish definitive treatment guidelines for this patient population.

BACKGROUND: Medium vessel occlusion (MeVO) strokes, particularly affecting the M2 segment of the middle cerebral artery, represent a critical proportion of acute ischemic strokes, posing significant challenges in management and outcome prediction. The efficacy of mechanical thrombectomy (MT) in MeVO stroke may warrant reliable predictors of functional outcomes. This study aimed to investigate the prognostic value of follow-up infarct volume (FIV) for predicting 90-day functional outcomes in MeVO stroke patients undergoing MT. METHODS: This multicenter, retrospective cohort study analyzed data from the Multicenter Analysis of primary Distal medium vessel occlusions: effect of Mechanical Thrombectomy (MAD-MT) registry, covering patients with acute ischemic stroke due to M2 segment occlusion treated with MT. We examined the relationship between 90-day functional outcomes, measured by the modified Rankin Scale (mRS), and follow-up infarct volume (FIV), assessed through CT or MRI within 12-36 h post-MT. RESULTS: Among 130 participants, specific FIV thresholds were identified with high specificity and sensitivity for predicting outcomes. A FIV ⩽5 ml was highly specific for predicting favorable and excellent outcomes. The optimal cut-off for both prognostications was identified at ⩽15 ml by the Youden Index, with significant reductions in the likelihood of favorable outcomes observed above a 40 ml threshold. Receiver Operator Curve (ROC) analyses confirmed FIV as a superior predictor of functional outcomes compared to traditional recanalization scores, such as final modified thrombolysis in cerebral infarction score (mTICI). Multivariable analysis further highlighted the inverse relationship between FIV and positive functional outcomes. CONCLUSIONS: FIV within 36 h post-MT serves as a potent predictor of 90-day functional outcomes in patients with M2 segment MeVO strokes. Establishing FIV thresholds may aid in the prognostication of stroke outcomes, suggesting a role for FIV in guiding post intervention treatment decisions and informing clinical practice. Future research should focus on validating these findings across diverse patient populations and exploring the integration of FIV measurements with other clinical and imaging markers to enhance outcome prediction accuracy.

BACKGROUND: Mechanical thrombectomy (MT) has revolutionized the treatment of acute ischemic stroke (AIS) due to large vessel occlusion (LVO), but its efficacy and safety in medium vessel occlusion (MeVO) remain less explored. This multicenter, retrospective study aims to investigate the incidence and clinical outcomes of vessel perforations (confirmed by extravasation during an angiographic series) during MT for AIS caused by MeVO. METHODS: Data were collected from 37 academic centers across North America, Asia, and Europe between September 2017 and July 2021. A total of 1373 AIS patients with MeVO underwent MT. Baseline characteristics, procedural details, and clinical outcomes were analyzed. RESULTS: The incidence of vessel perforation was 4.8% (66/1373). Notably, our analysis indicates variations in perforation rates across different arterial segments: 8.9% in M3 segments, 4.3% in M2 segments, and 8.3% in A2 segments (p = 0.612). Patients with perforation had significantly worse outcomes, with lower rates of favorable angiographic outcomes (TICI 2c-3: 23% vs 58.9%, p

While ChatGPT has recently become very popular, AI has a long history and philosophy. This paper intends to explore the promises and pitfalls of the Generative Pre-trained Transformer (GPT) AI and potentially future technologies by adopting a speculative methodology. Speculative future narratives with a specific focus on educational contexts are provided in an attempt to identify emerging themes and discuss their implications for education in the 21st century. Affordances of (using) AI in Education (AIEd) and possible adverse effects are identified and discussed which emerge from the narratives. It is argued that now is the best of times to define human vs AI contribution to education because AI can accomplish more and more educational activities that used to be the prerogative of human educators. Therefore, it is imperative to rethink the respective roles of technology and human educators in education with a future-oriented mindset.

INTRODUCTION: First pass effect (FPE), achievement of complete recanalization (mTICI 2c/3) with a single pass, is a significant predictor of favorable outcomes for endovascular treatment (EVT) in large vessel occlusion stroke (LVO). However, data concerning the impact on functional outcomes and predictors of FPE in medium vessel occlusions (MeVO) are scarce. PATIENTS AND METHODS: We conducted an international retrospective study on MeVO cases. Multivariable logistic modeling was used to establish independent predictors of FPE. Clinical and safety outcomes were compared between the two study groups (FPE vs non-FPE) using logistic regression models. Good outcome was defined as modified Rankin Scale 0-2 at 3 months. RESULTS: Eight hundred thirty-six patients with a final mTICI ⩾ 2b were included in this analysis. FPE was observed in 302 patients (36.1%). In multivariable analysis, hypertension (aOR 1.55, 95% CI 1.10-2.20) and lower baseline NIHSS score (aOR 0.95, 95% CI 0.93-0.97) were independently associated with an FPE. Good outcomes were more common in the FPE versus non-FPE group (72.8% vs 52.8%), and FPE was independently associated with favorable outcome (aOR 2.20, 95% CI 1.59-3.05). 90-day mortality and intracranial hemorrhage (ICH) were significantly lower in the FPE group, 0.43 (95% CI, 0.25-0.72) and 0.55 (95% CI, 0.39-0.77), respectively. CONCLUSION: Over 2/3 of patients with MeVOs and FPE in our cohort had a favorable outcome at 90 days. FPE is independently associated with favorable outcomes, it may reduce the risk of any intracranial hemorrhage, and 3-month mortality.

Abstract Background Immune cell metabolism governs the outcome of immune responses and contributes to the development of autoimmunity by controlling lymphocyte pathogenic potential. In this study, we evaluated the metabolic profile of myelin-specific murine encephalitogenic T cells, to identify novel therapeutic targets for autoimmune neuroinflammation. Methods We performed metabolomics analysis on actively-proliferating encephalitogenic T cells to study their overall metabolic profile in comparison to resting T cells. Metabolomics, phosphoproteomics, in vitro functional assays, and in vivo studies in experimental autoimmune encephalomyelitis (EAE), a mouse model of multiple sclerosis (MS), were then implemented to evaluate the effect of metabolic targeting on autoreactive T cell pathogenicity. Finally, we confirmed the translational potential of our targeting approach in human pro-inflammatory T helper cell subsets and in T cells from MS patients. Results We found that autoreactive encephalitogenic T cells display an altered coenzyme A (CoA) synthesis pathway, compared to resting T cells. CoA fueling with the CoA precursor pantethine (PTTH) affected essential immune-related processes of myelin-specific T cells, such as cell proliferation, cytokine production, and cell adhesion, both in vitro and in vivo. Accordingly, pre-clinical treatment with PTTH before disease onset inhibited the development of EAE by limiting T cell pro-inflammatory potential in vivo. Importantly, PTTH also significantly ameliorated the disease course when administered after disease onset in a therapeutic setting. Finally, PTTH reduced pro-inflammatory cytokine production by human T helper 1 (Th1) and Th17 cells and by T cells from MS patients, confirming its translational potential. Conclusion Our data demonstrate that CoA fueling with PTTH in pro-inflammatory and autoreactive T cells may represent a novel therapeutic approach for the treatment of autoimmune neuroinflammation.

The emergence of open educational resources (OER) represents one of the most significant educational developments in the 21st century. Given their capacity to be freely adapted, re-used, and shared in different contexts, OER expand the options for educators. This paper reports on an initial study concerning such choices in which educators' personalities are investigated in relation to the OER adoption. Choosing open approaches has been shown to correlate with personal attitudes and several studies have highlighted the potential and need for investigating how personality might affect OER adoption. To address this gap, this study investigates the impact of educators' personality differences in relation to OER adoption. The analysis focuses specifically on the perception towards OER and the intention to use OER using the Five-Factor Model (FFM) to identify educators' personalities. Following a mixed methods approach, data collected from university educators using questionnaires (57 respondents) and interviews (15 respondents) are discussed in a two-stage hierarchical regression analysis. Demographic variables (age and gender) do not show any significant relationship. Findings reveal that while the explored five personality dimensions do not have an impact on the educator attitudes towards OER, they seem to have a significant impact on their intention to use OER. Specifically, only three personality dimensions -- namely, extraversion, agreeableness, and openness -- have a significant impact on the intention to use OER. This shows that 'open attitude' (mixing extraversion, and agreeableness, and openness) may be a fundamental prerequisite for educators to engage in open teaching practices, including the use of OER.

In terms of scale, shock, and disenfranchisement, the disruption to formal education arising from COVID-19 has been unprecedented. Anecdotally, responses from teachers and educators around the world range from heightened caution to being inspired by distance education as the "new normal." Of all the challenges, face-to-face and formal teaching have been most heavily affected. Despite some education systems demonstrating resilience, a major challenge is sustaining quality and inclusiveness in formal education suddenly delivered at a distance. In probing these issues, this article profiles international perspectives on the role of open education in responding to the impact on formal school and higher education caused by the COVID-19 pandemic. We proceed by highlighting and analysing practices and case studies from 13 countries representing all global regions, identifying and discussing the challenges and opportunities that have presented themselves. Reports cover the period from the beginning of 2020 until 11 March 2021, the first anniversary of the COVID-19 outbreak as declared by the World Health Organization. In our comparative study, we identify seven key aspects of which three (missing infrastructure and sharing OER, open education and access to OER, and urgent need for professional development and training for teachers) are directly related to open education at a distance. After comparing examples of existing practice, we make recommendations and offer insights into how open education strategies can lead to interventions that are effective and innovative--to improve formal education at a distance in schools and universities in the future.

Background and Purpose The management of acute ischemic stroke (AIS) due to distal medium vessel occlusion (DMVO) remains uncertain, particularly in comparing the effectiveness of intravenous thrombolysis (IVT) plus mechanical thrombectomy (MT) versus IVT alone. This study aimed to evaluate the safety and efficacy in DMVO patients treated with either MT-IVT or IVT alone. Methods This multinational study analyzed data from 37 centers across North America, Asia, and Europe. Patients with AIS due to DMVO were included, with data collected from September 2017 to July 2023. The primary outcome was functional independence, with secondary outcomes including mortality and safety measures such as types of intracerebral hemorrhage. Results The study involved 1,057 patients before matching, and 640 patients post-matching. Functional outcomes at 90 days showed no significant difference between groups in achieving good functional recovery (modified Rankin Scale 0–1 and 0–2), with adjusted odds ratios (OR) of 1.21 (95% confidence interval [CI] 0.81 to 1.79; P=0.35) and 1.00 (95% CI 0.66 to 1.51; P>0.99), respectively. Mortality rates at 90 days were similar between the two groups (OR 0.75, 95% CI 0.44 to 1.29; P=0.30). The incidence of symptomatic intracerebral hemorrhage was comparable, but any type of intracranial hemorrhage was significantly higher in the MT-IVT group (OR 0.43, 95% CI 0.29 to 0.63; P

This manifesto critically examines the unfolding integration of Generative AI (GenAI), chatbots, and algorithms into higher education, using a collective and thoughtful approach to navigate the future of teaching and learning. GenAI, while celebrated for its potential to personalize learning, enhance efficiency, and expand educational accessibility, is far from a neutral tool. Algorithms now shape human interaction, communication, and content creation, raising profound questions about human agency and biases and values embedded in their designs. As GenAI continues to evolve, we face critical challenges in maintaining human oversight, safeguarding equity, and facilitating meaningful, authentic learning experiences. This manifesto emphasizes that GenAI is not ideologically and culturally neutral. Instead, it reflects worldviews that can reinforce existing biases and marginalize diverse voices. Furthermore, as the use of GenAI reshapes education, it risks eroding essential human elements—creativity, critical thinking, and empathy—and could displace meaningful human interactions with algorithmic solutions. This manifesto calls for robust, evidence-based research and conscious decision-making to ensure that GenAI enhances, rather than diminishes, human agency and ethical responsibility in education.

The development, use, and timely promotion of Open Education (OE) has been effective in addressing myriad educational concerns, including inclusivity, accessibility and learning achievement, among many others. However, limited information exists in the literature concerning how OE could enhance Generative Artificial Intelligence (GenAI), which is receiving extensive interest and criticism at this time. To address this research gap, this study relies on the Open Educational Practices (OEP) framework of Huang et al. (2020) to provide various OEP scenarios that could help to promote and facilitate the effective and safe adoption of GenAI in education. The findings of this study could provide guidelines on how relying on OEP when adopting GenAI could help in ensuring quality education which is the sustainable development goal (SDG 4) of the United Nations (UN).

Background Acute ischemic stroke arising from medium vessel occlusions (MeVO) poses substantial challenges in treatment and management. This study aims to elucidate the outcomes and factors contributing to achieving excellent recanalization (modified Thrombolysis in Cerebral Infarction [mTICI] 2c–3) versus successful recanalization (mTICI 2b) in patients with MeVO stroke undergoing mechanical thrombectomy (MT). Methods We conducted a multinational study analyzing data from the MAD‐MT (Multicenter Analysis of Distal Medium Vessel Occlusions: Effect of Mechanical Thrombectomy) registry, encompassing 37 centers across North America, Asia, and Europe, collected between September 2017 and July 2023. The study included acute ischemic stroke patients with MeVO treated with MT, with or without intravenous thrombolysis, who achieved mTICI 2b–3 post‐MT. Results Among 1463 patients with successful recanalization (mTICI 2b–3), 523 achieved mTICI 2b recanalization, and 940 achieved mTICI 2c–3. Distal occlusions exhibited higher odds of excellent recanalization compared with proximal MeVO vessel occlusions (odds ratio, 1.58; 95% CI, 1.17–2.15; P = 0.003). Cardioembolic stroke pathogenesis was associated with a higher likelihood of excellent recanalization (1.67; 95% CI, 1.07–2.59; P = 0.018). Patients achieving mTICI 2c–3 recanalization demonstrated lower initial National Institutes of Health Stroke Scale scores, significant improvements in postprocedural National Institutes of Health Stroke Scale shift, and a higher percentage of favorable 90‐day outcomes compared with those with mTICI 2b. However, no significant difference in 90‐day mortality rates was observed. Conclusion This study underscores that among patients with MeVO stroke with successful recanalization (mTICI 2b–3) there is higher likelihood of achieving excellent recanalization (mTICI 2c–3) in distal occlusions and cardioembolic pathogenesis. mTICI 2c–3 scores post‐MT correlate with improved clinical outcomes compared with mTICI 2b, affirming the superiority of excellent recanalization over successful recanalization in patients with MeVO stroke. Further prospective studies and randomized controlled trials are warranted for validation.

The introduction of open educational resources (OER) provides new opportunities for learners worldwide to access high-quality educational materials at the lowest cost. As a developing country, Vietnam is one of the countries that can most benefit from the OER movement. However, the concept of OER in Vietnam remains little known to the public, with few institutional OER repositories (IOER) developed. This study contends that IOER development in Vietnam is complicated and constrained by many contextual difficulties; it was designed to explore the challenges and opportunities. After a literature review, 20 semi-structured interviews were conducted with relevant stakeholders. Building on the findings from the literature, this study found that IOER development in Vietnam is constrained by five categories of challenges: (a) technological and infrastructure matters, (b) economic constraints, (c) sociocultural characteristics, (d) pedagogical concerns, and (e) legal limitations. Many of these challenges are not identified in the literature and provide insights into potential implications and solutions for future IOER in Vietnam and other countries.

Abstract Background To date, colchicine and prednisolone are two effective therapies for the treatment of acute gout but have never been compared directly in a randomized clinical trial. In addition, in previous trials of treating acute gout patients with concomitant comorbidities were often excluded due to contraindications to naproxen. Study design This pragmatic, prospective, double-blind, double-dummy, parallel-group, randomized, non-inferiority trial compares prednisolone with colchicine in terms of non-inferiority in patients with acute gout. Patients presenting to their general practitioner with acute gout can be included if the gout attack has occurred within the last 2 days. A total of 60 practices in the vicinity of three university medical centers (Greifswald, Göttingen, and Würzburg) participate in the study. The intervention group receives 30 mg prednisolone for 5 days, while the group of standard care receives low-dose colchicine (day 1: 1.5 mg; days 2–5: 1 mg). The first dose of treatment is provided at day 0 when patients present to the general practitioner due to an acute gout attack. From day 0 to day 6, patients will be asked to complete a study diary on daily basis regarding pain quantification. For safety reasons, potential side effects and the course of systolic blood pressure are also assessed. Statistical analysis plan N = 314 patients have to be recruited to compensate for 10% of dropout and to allow for showing non-inferiority of prednisolone compared to colchicine with a power of 90%. We use permuted block randomization with block sizes of 2, 4, and 6 to avoid imbalanced treatment arms in this multi-center study; patients are randomized in a 1:1 ratio. The absolute level of pain on day 3 (in the last 24 h) is the primary outcome and measured on a numerical rating scale (NRS: 0–10). Using a multiple linear regression model adjusted for age, sex, and pain at baseline, prednisolone is considered non-inferior if the effect estimate including the confidence intervals is lower than a margin of 1 unit on the NRS. Average response to treatment, joint swelling and tenderness, physical function of the joint, and patients’ global assessment of treatment success are secondary outcomes. Discussion The trial will provide evidence from a direct comparison of colchicine and prednisolone regarding their efficacy of pain reduction in acute gout patients of primary care and to indicate possible safety signals. Trial registration ClinicalTrials.gov Identifier: NCT05698680 first posted on January 26, 2023 (retrospectively registered).