Objective
This study was undertaken to identify temporal encephaloceles (TEs) and examine their characteristics in patients with temporal lobe epilepsy (TLE) and extratemporal lobe epilepsy (ETLE), ...as well as in asymptomatic cases.
Methods
Four hundred fifty‐eight magnetic resonance imaging scans were examined retrospectively to identify TE in 157 patients with TLE, 150 patients with ETLE, and 151 healthy controls (HCs).
Results
At least one TE was identified in 9.6% of the TLE patients (n = 15, 95% confidence interval CI = 5.3%–15.3%), in 3.3% of patients with ETLE (n = 5, 95% CI = 1.1%–7.6%), and in 2.0% of the HCs (n = 3, 95% CI = .4%–5.7%), indicating a significantly higher frequency in patients with TLE compared to ETLE and HC subjects (p = .027, p = .005). Examining the characteristics of TEs in both asymptomatic and epilepsy patients, we found that TEs with a diameter of less than 6.25 mm were more likely to be asymptomatic, with a sensitivity of 91.7% and a specificity of 73.3% (area under the curve = .867, 95% CI = .723–1.00, p = .001).
Significance
Temporal encephaloceles may occur without presenting any clinical symptoms. Patients with TLE show a higher frequency of TEs compared to the ETLE and HC groups. According to our study, TE size could be used to suggest potential epileptogenicity.
•The Singapore state changed its strategic role in engaging with foreign universities.•Singapore moved from importing global knowledge to fostering local skill formation.•More recently set up ...offshore campuses are more embedded in local skill formation.•Offshore campuses with high levels of embeddedness serve specifically local functions.
With operating offshore campuses, universities perform key education and training functions in regional economies worldwide. Few studies have acknowledged universities’ expanded role in knowledge and skill formation as both local providers and transnational managers of education and training. Not enough is known about the embedding of transnational universities in local skill formation and varying levels of embeddedness, as well as about the role of hosting states therein and consequences for local economies. This paper addresses this gap in the context of the city-state of Singapore, exploring how skill development at foreign universities has been locally embedded, and why this embeddedness of offshore campuses in local skill formation has changed over time. Empirical evidence is drawn from semi-structured interviews with managers of foreign university subsidiaries. It is found that the Singapore state has changed its role in engaging with foreign universities, from a first phase of importing ‘global’ knowledge in teaching and training to a second phase of strengthening ‘local’ knowledge and skill formation. With being distinctively more embedded than older offshore campuses, recently established subsidiaries perform specifically ‘local’ functions in Singapore’s progressing knowledge-based transformation project. The paper provides better understanding of varying/changing levels of offshore campus embeddedness and the interconnections between changing roles of the state, integration of foreign universities and regional development. A further contribution lies in presenting a conceptualisation of offshore campuses with high levels of embeddedness, helping shed light on the dynamics in local skill formation and in foreign actors’ functions for the regional economy more generally.
Universities from varying institutional and geographical contexts have increasingly invested in offshore subsidiaries in the Malaysian private higher education sector. Literature on transnational ...education policy and management as well as economic-geographic accounts of firms’ transnationalisation or public service provision have not investigated foreign providers’ direct investment and market access strategies in the higher education sector. This paper addresses these gaps, showing how and why foreign actors’ investment and market involvement in Malaysia have changed. Empirical data is drawn from qualitative interviews and policy documents. The research reveals that foreign universities have strategically modified their business partnerships and bi-national accreditation to bypass and bend state regulation of market access as well as to restructure internal organisation and geographical configuration. The paper proposes conceptualising foreign higher education providers as transnationalising, reflexive networks within networks that respond to dynamic market access regulation by adopting firm-like investment strategies.
Fostering innovation and upskilling labour pools have become key goals in national economic development plans and education and training system reforms since the mid‐1990s. For their transformation ...into knowledge‐based economies, countries in Southeast Asia have relied on importing transnational higher education providers and have envisioned themselves as international education hubs. As existing research from transnational education and higher education governance studies as well as economic geography and regional studies has not sufficiently addressed this nexus of transnational education and regional economic development, this paper investigates the role of foreign higher education institutions in economic development strategies in Malaysia and Singapore. It explores why and how states have strategically coupled their higher education systems with transnational education. The comparative case analysis draws on empirical evidence from 42 semi‐structured interviews. It finds that despite the two states' ostensibly similar ambitions to attract foreign higher education institutions, policies and outcomes differ strongly. Whereas in Malaysia a structural coupling led foreign subsidiaries to provide foreign degrees to domestic students and generate revenue in the private higher education sector, in Singapore foreign subsidiaries have been deployed strategically to upgrade the talent pool and public higher education system of the city‐state via functional coupling. Conceptualizing transnational education policies as forms of strategic coupling contributes to understanding their embeddedness within states' broader, historically formed economic development strategies.
Abstract
A female full-term newborn of 41 + 2 weeks gestational age with a respiratory adaptation disorder and hypercapnia was transferred from an external maternity clinic to our pediatric intensive ...care unit. The child is the second child of healthy, non-consanguineous parents. Multiple dysmorphias were noticed at arrival. We identified a choanal atresia/stenosis on both sides in the respiratory tract, a high palate, a submucous cleft palate, a bifid uvula, a laryngeal cleft and a bronchus suis. The child required intubation and ventilation. In addition, we recognized brachydactyly of the hands and feet. The phalanges were not visibly separable. There was nail hypoplasia and rocker bottom feet on both sides. Furthermore, we saw an anal atresia. In routine laboratory work-up, a hypoglycemia and not measurable low TSH serum concentration was noticed. Extended endocrinological laboratory diagnostics revealed a complete pituitary insufficiency. On cranial MRI, a large, iso- to slightly hyperintense space-occupying mass (3.8x3.7x2.5 cm3), originating from the hypothalamus was observed. The brainstem was displaced posteriorly by the mass. The imaging is consistent with a hypothalamic hamartoma. With regard to the present findings, we assumed an underlying genetic cause of the congenital malformations. As a clinical diagnosis, a Pallister-Hall syndrome was suspected. As described in our case, we saw the characteristic features: dysmorphia of the hands and feet, upper respiratory tract, anal atresia, and hypothalamic hamartomas. The Pallister-Hall syndrome is caused by mutations in the GLI3 gene on the 7p13 chromosome. It is inherited in an autosomal dominant manner and its prevalence is unknown. In our patient, a heterozygous, probably pathogenic variant in the GLI3-Gene was proven by Next Generation Sequencing (NGS).
Hepatocellular carcinoma (HCC) can have viral or non-viral causes
. Non-alcoholic steatohepatitis (NASH) is an important driver of HCC. Immunotherapy has been approved for treating HCC, but ...biomarker-based stratification of patients for optimal response to therapy is an unmet need
. Here we report the progressive accumulation of exhausted, unconventionally activated CD8
PD1
T cells in NASH-affected livers. In preclinical models of NASH-induced HCC, therapeutic immunotherapy targeted at programmed death-1 (PD1) expanded activated CD8
PD1
T cells within tumours but did not lead to tumour regression, which indicates that tumour immune surveillance was impaired. When given prophylactically, anti-PD1 treatment led to an increase in the incidence of NASH-HCC and in the number and size of tumour nodules, which correlated with increased hepatic CD8
PD1
CXCR6
, TOX
, and TNF
T cells. The increase in HCC triggered by anti-PD1 treatment was prevented by depletion of CD8
T cells or TNF neutralization, suggesting that CD8
T cells help to induce NASH-HCC, rather than invigorating or executing immune surveillance. We found similar phenotypic and functional profiles in hepatic CD8
PD1
T cells from humans with NAFLD or NASH. A meta-analysis of three randomized phase III clinical trials that tested inhibitors of PDL1 (programmed death-ligand 1) or PD1 in more than 1,600 patients with advanced HCC revealed that immune therapy did not improve survival in patients with non-viral HCC. In two additional cohorts, patients with NASH-driven HCC who received anti-PD1 or anti-PDL1 treatment showed reduced overall survival compared to patients with other aetiologies. Collectively, these data show that non-viral HCC, and particularly NASH-HCC, might be less responsive to immunotherapy, probably owing to NASH-related aberrant T cell activation causing tissue damage that leads to impaired immune surveillance. Our data provide a rationale for stratification of patients with HCC according to underlying aetiology in studies of immunotherapy as a primary or adjuvant treatment.
Despite the development of novel targeted drugs, the molecular heterogeneity of diffuse large B-cell lymphoma (DLBCL) still poses a substantial therapeutic challenge. DLBCL can be classified into at ...least 2 major subtypes (germinal center B cell GCB-like and activated B cell ABC-like DLBCL), each characterized by specific gene expression profiles and mutation patterns. Here we demonstrate a broad antitumor effect of dimethyl fumarate (DMF) on both DLBCL subtypes, which is mediated by the induction of ferroptosis, a form of cell death driven by the peroxidation of phospholipids. As a result of the high expression of arachidonate 5-lipoxygenase in concert with low glutathione and glutathione peroxidase 4 levels, DMF induces lipid peroxidation and thus ferroptosis, particularly in GCB DLBCL. In ABC DLBCL cells, which are addicted to NF-κB and STAT3 survival signaling, DMF treatment efficiently inhibits the activity of the IKK complex and Janus kinases. Interestingly, the BCL-2–specific BH3 mimetic ABT-199 and an inhibitor of ferroptosis suppressor protein 1 synergize with DMF in inducing cell death in DLBCL. Collectively, our findings identify the clinically approved drug DMF as a promising novel therapeutic option in the treatment of both GCB and ABC DLBCLs.
•As a result of low glutathione and glutathione peroxidase 4 levels and high 5-lipoxygenase expression, DMF induces ferroptosis in GCB DLBCL.•In ABC DLBCL, DMF induces succination of kinases IKK2 and JAK1, thus inhibiting NF-κB and JAK/STAT survival signaling.
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Research findings suggest that a significant proportion of individuals diagnosed with cancer, ranging from 25% to 60%, experience distress and require access to psycho-oncological services. Until ...now, only contemporary approaches, such as logistic regression, have been used to determine predictors of distress in oncological patients. To improve individual prediction accuracy, novel approaches are required. We aimed to establish a prediction model for distress in cancer patients based on a back propagation neural network (BPNN).
Retrospective data was gathered from a cohort of 3063 oncological patients who received diagnoses and treatment spanning the years 2011–2019. The distress thermometer (DT) has been used as screening instrument. Potential predictors of distress were identified using logistic regression. Subsequently, a prediction model for distress was developed using BPNN.
Logistic regression identified 13 significant independent variables as predictors of distress, including emotional, physical and practical problems. Through repetitive data simulation processes, it was determined that a 3-layer BPNN with 8 neurons in the hidden layer demonstrates the highest level of accuracy as a prediction model. This model exhibits a sensitivity of 79.0%, specificity of 71.8%, positive predictive value of 78.9%, negative predictive value of 71.9%, and an overall coincidence rate of 75.9%.
The final BPNN model serves as a compelling proof of concept for leveraging artificial intelligence in predicting distress and its associated risk factors in cancer patients. The final model exhibits a remarkable level of discrimination and feasibility, underscoring its potential for identifying patients vulnerable to distress.
Background & aims
To explore the humoral and T‐cell response to the third COVID‐19 vaccination in autoimmune hepatitis (AIH).
Methods
Anti‐SARS‐CoV‐2 antibody titers were prospectively determined in ...81 AIH patients and 53 healthy age‐ and sex‐matched controls >7 days (median 35) after the first COVID‐19 booster vaccination. The spike‐specific T‐cell response was assessed using an activation‐induced marker assay (AIM) in a subset of patients.
Results
Median antibody levels were significantly lower in AIH compared to controls (10 908 vs. 25 000 AU/ml, p < .001), especially in AIH patients treated with MMF (N = 14, 4542 AU/ml, p = .004) or steroids (N = 27, 7326 AU/ml, p = .020). Also, 48% of AIH patients had antibody titers below the 10% percentile of the healthy controls (9194 AU/ml, p < .001). AIH patients had a high risk of failing to develop a spike‐specific T‐cell response (15/34 (44%) vs. 2/16 (12%), p = .05) and showed overall lower frequencies of spike‐specific CD4 + T cells (median: 0.074% vs 0.283; p = .01) after the booster vaccination compared to healthy individuals. In 34/81 patients, antibody titers before and after booster vaccination were available. In this subgroup, all patients but especially those without detectable/low antibodies titers (<100 AU/ml) after the second vaccination (N = 11/34) showed a strong, 148‐fold increase.
Conclusion
A third COVID‐19 vaccination efficiently boosts antibody levels and T‐cell responses in AIH patients and even seroconversion in patients with the absent immune response after two vaccinations, but to a lower level compared to controls. Therefore, we suggest routinely assessing antibody levels in AIH patients and offering additional booster vaccinations to those with suboptimal responses.