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In an effort to understand the impact of the international education network, Teach for All, this paper focuses on one Teach For All affiliate program, Ako Matatupu/TFNZ (AM/TFNZ), to consider how Teach For All and its affiliates are reshaping notions of teacher expertise and professionalism as it defines itself in contrast to university-based teacher education. In an effort to understand the impact of the international education network, Teach for All, this paper focuses on one Teach For All affiliate program, Ako Matatupu/TFNZ (AM/TFNZ), to consider how Teach For All and its affiliates are reshaping notions of teacher expertise and professionalism as it defines itself in contrast to university-based teacher education.

In recent years, Artificial Intelligence has been used to assist healthcare professionals in detecting and diagnosing neurodegenerative diseases. In this study, we propose a methodology to analyze functional Magnetic Resonance Imaging signals and perform classification between Parkinson’s disease patients and healthy participants using Machine Learning algorithms. In addition, the proposed approach provides insights into the brain regions affected by the disease. The functional Magnetic Resonance Imaging from the PPMI and 1000-FCP datasets were pre-processed to extract time series from 200 brain regions per participant, resulting in 11,600 features. Causal Forest and Wrapper Feature Subset Selection algorithms were used for dimensionality reduction, resulting in a subset of features based on their heterogeneity and association with the disease. We utilized Logistic Regression and XGBoost algorithms to perform PD detection, achieving 97.6% accuracy, 97.5% F1 score, 97.9% precision, and 97.7%recall by analyzing sets with fewer than 300 features in a population including men and women. Finally, Multiple Correspondence Analysis was employed to visualize the relationships between brain regions and each group (women with Parkinson, female controls, men with Parkinson, male controls). Associations between the Unified Parkinson’s Disease Rating Scale questionnaire results and affected brain regions in different groups were also obtained to show another use case of the methodology. This work proposes a methodology to (1) classify patients and controls with Machine Learning and Causal Forest algorithm and (2) visualize associations between brain regions and groups, providing high-accuracy classification and enhanced interpretability of the correlation between specific brain regions and the disease across different groups.

The IMPACC cohort, composed of >1,000 hospitalized COVID-19 participants, contains five illness trajectory groups (TGs) during acute infection (first 28 days), ranging from milder (TG1-3) to more severe disease course (TG4) and death (TG5). Here, we report deep immunophenotyping, profiling of >15,000 longitudinal blood and nasal samples from 540 participants of the IMPACC cohort, using 14 distinct assays. These unbiased analyses identify cellular and molecular signatures present within 72 h of hospital admission that distinguish moderate from severe and fatal COVID-19 disease. Importantly, cellular and molecular states also distinguish participants with more severe disease that recover or stabilize within 28 days from those that progress to fatal outcomes (TG4 vs. TG5). Furthermore, our longitudinal design reveals that these biologic states display distinct temporal patterns associated with clinical outcomes. Characterizing host immune responses in relation to heterogeneity in disease course may inform clinical prognosis and opportunities for intervention.

One of the pharmacological approaches to neoplastic disease aims to target the metastatic capacity of tumor cells to reduce their aggressive behavior. In this study, we analyzed the antimigratory capacity of the compound SEMBL, (S)-β-salicyloylamino-a-exo-methylene-ƴ-butyrolactone, a new analog of (-)-Dehydroxymethylepoxyquinomicin ((-)-DHMEQ), in three different breast cancer cell lines: MCF-7, MCF-7R and MDA-MB-231. This molecule is characterized by intense antiproliferative activity, evaluated by MTS assay, showing greater potency than DHMEQ. SEMBL was able to inhibit nuclear factor κappa B (NF-κB) activation observed through TransAM™ assay, while cell invasion and wound healing assays revealed a strong reduction in invasive capacity mediated by metalloproteinase 2 (MMP-2) and Vimentin decrease. These results, obtained in vitro, were corroborated on 3D systems made up of Poly-L-Lactic Acid (PLLA) scaffolds. In summary, SEMBL exerts interesting anti-tumor activities in preclinical breast cancer models and therefore it could be a promising new molecule to be studied also in other types of neoplastic disease.

Statistically significant violations of the Clauser–Horne–Shimony–Holt (CHSH) inequality are the “gold standard” test for quantum entanglement between spatially separated systems. Here, we report an experimental design that implements a CHSH test between bioelectric state variables for a human subject and bioelectric and/or biochemical state variables for cultured human cells in vitro. While we were unable to obtain evidence for entanglement with this design, observing only classical correlation, we report lessons learned and suggest possible avenues for future studies.

We have reported the case of a 36-year-old man with severe scrotal swelling that had remained undiagnosed after multiple diagnostic tests. The patient had presented with scrotal swelling, multiple weeping ulcers on the dorsal aspect of the scrotum, and worsening pain affecting his day-to-day functioning. Duplex ultrasound showed low- to no-flow hypervascularity and dependent edema suspicious for a vascular malformation. Treatment included sequential Gelfoam (Pfizer, New York, NY) embolization using ultrasound-guided direct cannulation and traditional angiography. The scrotal circumference decreased by 65%, with moderate relief of his pain. The details from the present case have highlighted the significance of vascular malformations, various diagnostic and therapeutic techniques used, and value of endovascular embolization.

Abstract The glycosylation of IgG plays a critical role during human severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, activating immune cells and inducing cytokine production. However, the role of IgM N-glycosylation has not been studied during human acute viral infection. The analysis of IgM N-glycosylation from healthy controls and hospitalized coronavirus disease 2019 (COVID-19) patients reveals increased high-mannose and sialylation that correlates with COVID-19 severity. These trends are confirmed within SARS-CoV-2-specific immunoglobulin N-glycan profiles. Moreover, the degree of total IgM mannosylation and sialylation correlate significantly with markers of disease severity. We link the changes of IgM N-glycosylation with the expression of Golgi glycosyltransferases. Lastly, we observe antigen-specific IgM antibody-dependent complement deposition is elevated in severe COVID-19 patients and modulated by exoglycosidase digestion. Taken together, this work links the IgM N-glycosylation with COVID-19 severity and highlights the need to understand IgM glycosylation and downstream immune function during human disease.

Background/Objectives: A key role of extracellular vesicles (EVs) is mediating both cell–cell and cell–stroma communication in pathological/physiological conditions. EVs from resistant tumor cells can transport different molecules like P-glycoprotein (P-gp), acting as a shuttle between donor and recipient cells, resulting in a phenotypic change. The aim of our work was to isolate, characterize, and inhibit the release of EVs in two multidrug resistance (MDR) cancer models: MCF-7R (breast cancer cell line) and HL-60R (acute myeloid leukemia cell line). Methods: The existence of P-gp in EVs from MDR cells was confirmed by Western blotting assays. The characterization of EVs was carried out by evaluating the size using NTA and the presence of specific markers such as CD63, Hsp70 and Syntenin. The ability of HL-60R and MCF-7R to perform horizontal transfer of P-gp via EVs to sensitive cells was assessed using three different methods. The acquisition of resistance and its inhibition in recipient cells was confirmed by MTS 3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium (MTS) assay. Results: Our data showed that cell lines (MDR) release P-gp-loaded EVs, unlike sensitive cells. The acquisition of resistance determined by the incorporation of P-gp into the membrane of sensitive cells was confirmed by the reduced cytotoxic activity of doxorubicin. Natural compounds such as curcumin, lupeol, and heptacosane can block vesicular transfer and restore the sensitivity of HL-60 and MCF-7 cells. Conclusions: Our study demonstrates that natural inhibitors able to reverse this mechanism may represent a new therapeutic strategy to limit the propagation of the resistant phenotype.

This study investigates the effectiveness of a 6-month parent-mediated early intervention telehealth program for children with an autism spectrum disorder. The participants comprised a total of 27 parents. The findings showed that participation in the program promotes parents' empowerment and reduce parental stress and a general improvement in the parents' ability to stimulate children's learning. Moreover, the study reveals an effect of parents' age in mediating the relationship among the parents' ability, stress, and empowerment levels. These results suggest that an early intervention telehealth program may help parents become aware of how to benefit from interactions with their children, promote their empowerment, and reduce parenting stress.

IntroductionMeningioma is the most common primary intracranial tumour in adults. The majority are non-malignant, but a proportion behave more aggressively. Incidental/minimally symptomatic meningioma are often managed by serial imaging. Symptomatic meningioma, those that threaten neurovascular structures, or demonstrate radiological growth, are usually resected as first-line management strategy. For patients in poor clinical condition, or with inoperable, residual or recurrent disease, radiotherapy is often used as primary or adjuvant treatment. Effective pharmacotherapy treatments do not currently exist. There is heterogeneity in the outcomes measured and reported in meningioma clinical studies. Two 'Core Outcome Sets' (COS) will be developed: (COSMIC: Intervention) for use in meningioma clinical effectiveness trials and (COSMIC: Observation) for use in clinical studies of incidental/untreated meningioma.Methods and analysisTwo systematic literature reviews and trial registry searches will identify outcomes measured and reported in published and ongoing (1) meningioma clinical effectiveness trials, and (2) clinical studies of incidental/untreated meningioma. Outcomes include those that are clinician reported, patient reported, caregiver reported and based on objective tests (eg, neurocognitive tests), as well as measures of progression and survival. Outcomes will be deduplicated and categorised to generate two long lists. The two long lists will be prioritised through two, two-round, international, modified eDelphi surveys including patients with meningioma, healthcare professionals, researchers and those in caring/supporting roles. The two final COS will be ratified through two 1-day online consensus meetings, with representation from all stakeholder groups.Ethics and disseminationInstitutional review board (University of Liverpool) approval was obtained for the conduct of this study. Participant eConsent will be obtained prior to participation in the eDelphi surveys and consensus meetings. The two systematic literature reviews and two final COS will be published and freely available.Trial registration numberCOMET study ID 1508.

IntroductionDespite the association between cannabis use and higher prevalence of suicidal ideation and attempt, the effect of cannabis legalization and regulation in Canada on intentional self-harm has not been determined. MethodsWe used an interrupted time series of population-based rates of emergency department (ED) visits and hospitalizations for intentional self-harm per 100 000 in Ontario and Alberta from January/April 2010 to February 2020. Aggregate monthly counts of ED visits and hospitalizations for intentional self-harm (ICD-10 codes X60–X84, R45.8) were obtained from the National Ambulatory Care Reporting System and Discharge Abstract Database, respectively. ResultsThe legalization and regulation of cannabis in Canada was not significantly associated with a change in rates of ED visits for intentional self-harm in Ontario (level = 0.58, 95% CI: −1.14 to 2.31; trend = −0.17, 95% CI: −0.35 to 0.01) or Alberta (level = −0.06, 95% CI: −2.25 to 2.12; trend = −0.07, 95% CI: −0.27 to 0.13). Hospitalizations for intentional self-harm also remained unchanged in Ontario (level = −0.14, 95% CI: −0.48 to 0.20; trend = 0.01, 95% CI: −0.03 to 0.04) and Alberta (level = −0.41, 95% CI: −1.03 to 0.21; trend = −0.03, 95% CI: −0.08 to 0.03). ConclusionLegalization and regulation of cannabis in Canada has not increased rates of ED visits or hospitalizations for intentional self-harm in Ontario and Alberta. Individual-level analyses that account for demographic characteristics and include other provinces and territories are needed.

IntroductionMalgré l’association connue entre consommation de cannabis et prévalence accrue d’idées suicidaires et de tentatives de suicide, on n’a pas encore mesuré l’effet de la légalisation et de la réglementation du cannabis au Canada sur les lésions auto-infligées. MéthodologieNous avons utilisé des séries chronologiques interrompues des taux de consultation aux urgences et d’hospitalisation pour lésions auto-infligées pour 100 000 habitants en Ontario et en Alberta entre janvier ou avril 2010 et février 2020. Les effectifs mensuels globaux de consultations aux urgences et d’hospitalisations pour lésions auto-infligées (codes X60-X84 et R45.8 selon la CIM-10) ont été obtenus grâce respectivement au Système national d’information sur les soins ambulatoires et à la Base de données sur les congés des patients. RésultatsLa légalisation et la réglementation du cannabis au Canada n’ont pas été associées de manière statistiquement significative à une modification des taux de consultation aux urgences pour lésions auto-infligées en Ontario (niveau = 0,58 avec IC à 95 % : −1,14 à 2,31; tendance = −0,17 avec IC à 95 % : −0,35 à 0,01) ou en Alberta (niveau = −0,06 avec IC à 95 % : −2,25 à 2,12; tendance = −0,07 avec IC à 95 % : −0,27 à 0,13). Les hospitalisations pour lésions auto-infligées sont également demeurées inchangées en Ontario (niveau = −0,14 avec IC à 95 % : −0,48 à 0,20; tendance = 0,01 avec IC à 95 % : −0,03 à 0,04) et en Alberta (niveau = −0,41 avec IC à 95 % : −1,03 à 0,21; tendance = −0,03 avec IC à 95 % : −0,08 à 0,03). ConclusionLa légalisation et la réglementation du cannabis au Canada n’ont pas entraîné d’augmentation des taux de consultation aux urgences ou d’hospitalisation pour lésions auto-infligées en Ontario ou en Alberta. Des analyses à l’échelle individuelle tenant compte des caractéristiques individuelles et incluant d’autres provinces et territoires sont nécessaires.

It is commonly believed that expressions visually signal rich diagnostic information to human observers. We studied how observers interpret the dynamic expressions that people spontaneously produced during a real-life high-stakes televised game. We find that human observers are remarkably poor at recovering what events elicited others' facial and bodily expressions. Beyond simple inaccuracy, people's causal reasoning exhibits systematic model-based patterns of errors. We show that latent emotion representations can explain people's reasoning about the unseen causes of expressions. A hierarchical Bayesian model simulates which events people infer to be the cause of others' expressions by comparing the emotions inferred from the expressions against the emotions people were predicted to experience in various situations. This causal model provides a close, parameter-free fit to human causal judgments, suggesting that humans interpret expressions in the context of emotion predictions generated by a causally-structured mental model of other minds.

Oxidative stress plays a central role in most chronic liver diseases and, in particular, in metabolic dysfunction-associated fatty liver disease (MAFLD), the new definition of an old condition known as non-alcoholic fatty liver disease (NAFLD). The mechanisms leading to hepatocellular fat accumulation in genetically predisposed individuals who adopt a sedentary lifestyle and consume an obesogenic diet progress through mitochondrial and endoplasmic reticulum dysfunction, which amplifies reactive oxygen species (ROS) production, lipid peroxidation, malondialdehyde (MDA) formation, and influence the release of chronic inflammation and liver damage biomarkers, such as pro-inflammatory cytokines. This close pathogenetic link has been a key stimulus in the search for therapeutic approaches targeting oxidative stress to treat steatosis, and a number of clinical trials have been conducted to date on subjects with NAFLD using drugs as well as supplements or nutraceutical products. Vitamin E, Vitamin D, and Silybin are the most studied substances, but several non-pharmacological approaches have also been explored, especially lifestyle and diet modifications. Among the dietary approaches, the Mediterranean Diet (MD) seems to be the most reliable for affecting liver steatosis, probably with the added value of the presence of extra virgin olive oil (EVOO), a healthy food with a high content of monounsaturated fatty acids, especially oleic acid, and variable concentrations of phenols (oleocanthal) and phenolic alcohols, such as hydroxytyrosol (HT) and tyrosol (Tyr). In this review, we focus on non-pharmacological interventions in MAFLD treatment that target oxidative stress and, in particular, on the role of EVOO as one of the main antioxidant components of the MD.

American and European adults prefer natural products and often pay premiums to purchase natural products. They may do this because they believe natural products are better, either functionally or inherently. We present a measure that assesses belief in the ‘benevolence of nature’ across a range of products and a range of situations, including safety, sensory appeal, and effectiveness. American adults show a substantial belief in the benevolence of nature. This belief is sometimes erroneous, with participants attributing higher quality to some natural products that are in fact inferior to their artificial counterparts. In support of the belief that natural products are inherently better, many participants express a preference for a natural as opposed to an artificial product when both are stipulated to be chemically identical or to have identical effects. An original set of 24 items to measure belief in the benevolence of nature is refined into a more useful 10-item scale, and correlations with related scales are assessed. Belief in the benevolence of nature is not lower in participants who have experienced at least one natural disaster.

In the field of immunology, a systems biology approach is crucial to understanding the immune response to infection and vaccination considering the complex interplay between genetic, epigenetic, and environmental factors. Significant progress has been made in understanding the innate immune response, including cell players and critical signaling pathways, but many questions remain unanswered, including how the innate immune response dictates host/pathogen responses and responses to vaccines. To complicate things further, it is becoming increasingly clear that the innate immune response is not a linear pathway but is formed from complex networks and interactions. To further our understanding of the crosstalk and complexities, systems-level analyses and expanded experimental technologies are now needed. In this review, we discuss the most recent immunoprofiling techniques and discuss systems approaches to studying the global innate immune landscape which will inform on the development of personalized medicine and innovative vaccine strategies.

Background: Osteoarthritis (OA) of the knee is an inflammatory joint disorder of the cartilage, joint capsule, synovium, and surrounding bone. Intraarticular inflammation induces angiogenesis leading to pain and inflammation. Research suggests a relationship between patients with osteoarthritis of the knee and venous insufficiency or contributing arteriovenous malformations (AVMs). Similar to genicular artery embolization (GAE), transvenous or transmalformation cannulation and embolization offers a minimally invasive treatment modality for patients with mild to moderate osteoarthritis. Case presentations: Here, we present the successful treatment of OA of the knee using direct puncture transmalformation cannulation and embolization in five patients. Direct puncture, a technique used to embolize peripheral AVMs, is a safe, less invasive method for the treatment of osteoarthritis with associated AVMs. Conclusions: For patients with OA-related knee pain and associated AVMs, the advancement of endovascular techniques offers alternative approaches to the treatment of mild to moderate OA. Direct puncture and transmalformation cannulation and embolization reduce the risk of intra- and post-operative complications, improve recovery time, and minimize operating time and operating costs. In review of the literature, this is one of the first published reports describing the use of direct puncture transvenous or transmalformation cannulation and embolization to treat OA-related pain.

Uterine leiomyomas are the most common benign pelvic tumors in premenopausal women, causing significant morbidity. Uterine fibroid embolization is a minimally invasive alternative to traditional open or laparoscopic surgeries for the management of symptomatic uterine leiomyoma. For large fibroids, hospitalization after treatment is often required. However, there are limited data on patients with large, complex uterine leiomyomas treated by embolization. This report of 2 cases describes 2 females with large, complex fibroids causing pain and decreased quality of life who were evaluated and treated with embolization in the outpatient setting. Each patient underwent transradial cannulation and uterine artery embolization under local anesthesia or conscious sedation and returned home without complication. For women wishing to preserve their uterus, uterine fibroid embolization is an effective nonsurgical alternative to hysterectomy and myomectomy in an outpatient setting. If standard protocols are followed, embolization by way of transradial artery catheterization is safe for the treatment of large, complex, symptomatic fibroids in the outpatient setting; however, additional studies with larger cohorts are warranted. Accessing the uterine arteries transradially reduces the risk of intra- and post-operative complications for patients, reduces their time spent in a hospital, and minimizes operating costs.