Miracle-dz/UniFAR-FTUs huggingface dataset:
Vascular endothelial growth factor promotes transdifferentiation of astrocytes into neurons via activation of the MAPK/Erk‐Pax6 signal pathway

Reactive astrocytes can be transformed into new neurons. Vascular endothelial growth factor (VEGF) promotes the transformation of reactive astrocytes into neurons in ischemic brain. Therefore, in this study, the molecular mechanism of VEGF's effect on ischemia/hypoxia‐induced astrocyte to neuron transformation was investigated in the models of rat middle cerebral artery occlusion (MCAO) and in astrocyte culture with oxygen and glucose deprivation (OGD). We found that VEGF enhanced ischemia‐induced Pax6, a neurogenic fate determinant, expression and Erk phosphorylation in reactive astrocytes and reduced infarct volume of rat brain at 3 days after MCAO, which effects could be blocked by administration of U0126, a MAPK/Erk inhibitor. In cultured astrocytes, VEGF also enhanced OGD‐induced Erk phosphorylation and Pax6 expression, which was blocked by U0126, but not wortmannin, a PI3K/Akt inhibitor, or SB203580, a MAPK/p38 inhibitor, suggesting VEGF enhanced Pax6 expression via activation of MAPK/Erk pathway. OGD induced the increase of miR365 and VEGF inhibited the increase of OGD‐induced miR365 expression. However, miR365 agonists blocked VEGF‐enhanced Pax6 expression in hypoxic astrocytes, but did not block VEGF‐enhanced Erk phosphorylation. We further found that VEGF promoted OGD‐induced astrocyte‐converted to neuron. Interestingly, both U0126 and Pax6 RNAi significantly reduced enhancement of VEGF on astrocytes‐to‐neurons transformation, as indicated Dcx and MAP2 immunopositive signals in reactive astrocytes. Moreover, those transformed neurons become mature and functional. We concluded that VEGF enhanced astrocytic neurogenesis via the MAPK/Erk‐miR‐365‐Pax6 signal axis. The results also indicated that astrocytes play important roles in the reconstruction of neurovascular units in brain after stroke.
Exploring the Irish general practice training community’s perceptions on how an entrustable professional activities dashboard implementation could facilitate general practice training in Ireland

ABSTRACT Background The Irish General Practitioner Training (GP) Programme is currently moving to Competency-Based Medical Education (CBME), facilitated by Programmatic Assessment (PA) and Entrustable Professional Activities (EPAs). These new assessment and feedback mechanisms may provide a rich and much sought-after dataset. However, given the possible number of feedback and assessment events, and the variety of modalities used, aggregating and interpreting these can be costly and difficult. Dashboard implementations (DI) have been purposed as a solution to bridge the gap between the large datasets and the training community at all levels. Aims To explore the Irish GP training community’s perceptions on how an EPAs DI could facilitate the delivery of GP training in Ireland. Methods A qualitative approach was taken, using a focus group representative of different groups in the training community. Concurrently, an EPAs DI was developed. Focus group transcripts were analysed in an iterative fashion using Template Analysis to generate themes and subthemes. Results Numerous advantages were seen in relation to the implementation of an EPAs DI around entrustment decisions, constructive alignment and summative decision-making. These advantages, however, need to be tempered with the realisation that the EPAs DI is not and should not be misinterpreted as being the learning analytic panacea for GP training. Conclusion This paper outlines the perceptions from a postgraduate medical education training community on an EPAs DI, which would be applicable to other training communities considering introducing similar mechanisms.
Decomposing the predictive performance of the moving average trading rule of technical analysis: the contribution of linear and non-linear dependencies in stock returns

The main purpose of this work is to decompose the predictive performance of the moving average (MA) trading rule and find out the portion that could be attributed to the possible exploitation of linear and non-linear dependencies in stock returns. Data from the General Index of the Athens Stock Exchange, from the Standard and Poor-500 Index of the New York Stock Exchange and from the Austrian Traded Index of the Vienna Stock Exchange are filtered by linear filters so as the resulting simulated ‘returns’ exhibit no serial correlation. Applying MA trading rules to both the original and the simulated indices and using a new statistical testing procedure that takes into account the sensitivity of the performance of the trading rule as a function of the length of the MA it is found that the predictive performance of the trading rule is clearly weakened when applied to the simulated indices indicating that a substantial part of the rule's predictive performance is due to the exploitation of linear dependencies in stock returns. This weakening is uneven; in general the shorter the MA length the more pronounced the attenuation.
Absorbed Dose Measurement and LET Determination with TLDs in Space

For determination of the average LET in complex mixed radiation fields, a new method was developed using the LET dependent changes of the peak height ratios in thermoluminescence glow curves (HTR). Various types of standard and laboratory made TLDs were calibrated in alpha, beta, gamma and neutron fields and in heavy charged particle beams. These calibrated TL phosphors were used on space station MIR in order to determine the equivalent dose. During the long-term mission of 5 months in the summer of 1991 the dose rate was 0.24 ± 0.01 mGy.d -1 with an average LET (tissue) of 6.2 ± 0.25 keV. μm -1 , and during an 8 day short-term mission in October 1991 0.204 ± 0.003 mGy.d -1 with a LET of 6.5 ± 0.30keV. μm -1 . The new method was also used for measurements carried out on satellite PHOTON-8 (1992) and on satellite BION-10 (1993) to obtain more information about the changes of the average LET of space radiation with the variation of the shielding. An increase in the average LET from 0.35 to 10keV. μL -1 dependent on the absorber thickness from 1,14mg.cm -2 to 2.5 g.cm -2 was measured. The method was also used for determination of the characteristics of the low energy electron component of space radiation on BION-10 and for the determination of the average LET on board high altitude aircraft.
Development and validation of a novel screening instrument to prioritize the orthodontic referral of developing malocclusion in children: The index for interceptive orthodontics referral

Objective The absence of a guideline to refer developing malocclusions appropriately, may be a contributing factor to the inadequacy of timely interceptive orthodontics provision. This study aimed to develop and validate a new orthodontic grading and referral index to be used by dental frontliners to prioritize the orthodontic referral of developing malocclusion in children based on its severity. Methods A cross-sectional study involving clinical assessment with 413 schoolchildren aged between 8.1 and 11.9 years was conducted in 2018. All the presenting malocclusion was listed and graded based on a few dental guidelines to produce the draft index. The validity and reliability of the draft index were tested using twenty study models. Face and content validation was carried out using the content validation index and Modified Kappa Statistics. Results Fourteen dental and occlusal anomalies were identified as components of malocclusion and three grades of referral (monitor, standard, urgent) were included in the final index. The scale-level content validity index average value of 0.86 and 0.87 was obtained for content and face validation, respectively. There was moderate to excellent agreement in the Modified Kappa Statistics for both validations. Excellent inter- and intra-assessor agreement was obtained. The new index displayed valid and reliable scores. Conclusions The Index for Interceptive Orthodontics Referral was developed and validated for the dental frontliners to identify and prioritize the developing malocclusion in children based on its severity and refer for orthodontic consultation to increase the possibility for interceptive orthodontics.
PFAS, bisphenol, and paraben in Malaysian food and estimated dietary intake

ABSTRACT Endocrine disrupting chemicals (EDCs) such as per- and polyfluoroalkyl substances (PFAS), bisphenols, and parabens are used in food packaging or as preservatives and their unintended consumption has been associated with cancer and other diseases. Food EDCs data are scarce in Malaysia. Thus, liquid chromatography mass tandem spectrometry (LC-MS/MS) was utilised to analyse 18 EDCs from different food categories. Bisphenol was the most abundant EDC found, followed by PFAS and paraben. Bisphenol levels in canned foods, dairy products, canned drinks, fruits, and vegetables ranged from 1.16 to 183 ng/g. PFAS was found in almost every food category, with canned foods having the highest concentrations (0.18–34.5 ng/g). Only canned foods, fruits, and vegetables contained parabens, with mean concentrations ranging from 0.27 to 26.7 ng/g. PFOS, PFBA, PFHQA and bisphenol A all had hazard quotients (HQ) above 1, indicating that they can pose a risk to human health.
The Relations between Narrative Identity and Personality Pathology among Clinical Adolescents: Findings from a Multi-Ethnic Asian Sample

Abstract Adolescence is a period where personality difficulties can start emerging. At the same time, a great deal of development in narrative identity takes place. Given that identity impairments are a key feature in personality pathology, it is useful to understand how pathological traits and narrative identity features are related. The current study addressed this by linking pathological personality trait domains to narrative identity features in clinically-referred Singaporean adolescents. Participants (n = 118, Mage = 16.82) wrote narratives about a turning point in their lives. These narratives were coded for themes of agency, communion, self-event connection, redemption, and coherence. Communion was significantly and substantially associated with pathological trait domains of negative affectivity, detachment, disinhibition, and psychoticism, although the effect sizes were modest. Whether a lack of communion themes contribute to the development of personality pathology or whether the former is an expression of the latter is an open question for future research.
Neuropsychological evaluation of phenoconversion risk in REM sleep behaviour disorder: A scoping review

The objective of this study was to assess the role of cognitive evaluation in the prediction of phenoconversion in polysomnography‐confirmed idiopathic or isolated rapid eye movement sleep behaviour disorder, through a scoping review focussing on a longitudinal comprehensive neuropsychological assessment of patients with idiopathic REM sleep behaviour disorder. A literature search (2006–2022) yielded 1034 records, and 20 were selected for analysis. The sample included 899 patients from eight different cohorts and five countries. We extracted data on clinical evolution, mild cognitive impairment diagnosis, neuropsychological tests used, and classification of cognitive domains. Tests, cognitive domains, and mild cognitive impairment definitions were heterogeneous across the studies, precluding a meta‐analysis. Ten studies (50%) evaluated the presence of mild cognitive impairment; 14 studies (70%) grouped neuropsychological tests into between three (6 studies, 21.4%) and seven (1 study, 7.1%) cognitive domains. The most frequently used tests were semantic fluency, Stroop colour word test, trail making test A and B, digit span, Rey auditory verbal learning test, and Rey‐Osterrieth figure. All except digit span showed a role in predicting phenoconversion. The authors did not consistently assign tests to specific cognitive domains. In conclusion, we discuss methodological differences between the studies and highlight the need for a standardised framework for neuropsychological data acquisition and presentation, based on a multilevel approach covering test selection, domain assignment, and mild cognitive impairment diagnostic criteria.
Shifting the sociometer: opioid receptor blockade lowers self-esteem

Abstract Given the evolutionary importance of social ties for survival, humans are thought to have evolved psychobiological mechanisms to monitor and safeguard the status of their social bonds. At the psychological level, self-esteem is proposed to function as a gauge—‘sociometer’—reflecting one’s social belongingness status. At the biological level, endogenous opioids appear to be an important substrate for the hedonic signalling needed to regulate social behaviour. We investigated whether endogenous opioids may serve as the biological correlate of the sociometer. We administered 50 mg naltrexone (an opioid receptor antagonist) and placebo in a counterbalanced order to 26 male and female participants on two occasions ∼1 week apart. Participants reported lower levels of self-esteem—particularly self-liking—on the naltrexone (vs placebo) day. We also explored a potential behavioural consequence of naltrexone administration: attentional bias to accepting (smiling) faces—an early-stage perceptual process thought to maximize opportunities to restore social connection. Participants exhibited heightened attentional bias towards accepting faces on the naltrexone (vs placebo) day, which we interpret as an indicator of heightened social need under opioid receptor blockade. We discuss implications of these findings for understanding the neurobiological underpinnings of sociality as well as the relationship between adverse social conditions, low self-esteem and psychopathology.
Programming CAR T Cell Tumor Recognition: Tuned Antigen Sensing and Logic Gating

Abstract The success of chimeric antigen receptor (CAR) T cells targeting B-cell malignancies propelled the field of synthetic immunology and raised hopes to treat solid tumors in a similar fashion. Antigen escape and the paucity of tumor-restricted CAR targets are recognized challenges to fulfilling this prospect. Recent advances in CAR T cell engineering extend the toolbox of chimeric receptors available to calibrate antigen sensitivity and combine receptors to create adapted tumor-sensing T cells. Emerging engineering strategies to lower the threshold for effective antigen recognition, when needed, and enable composite antigen recognition hold great promise for overcoming tumor heterogeneity and curbing off-tumor toxicities. Significance: Improving the clinical efficacy of CAR T cell therapies will require engineering T cells that overcome heterogeneous and low-abundance target expression while minimizing reactivity to normal tissues. Recent advances in CAR design and logic gating are poised to extend the success of CAR T cell therapies beyond B-cell malignancies.
Every Endomorphism of a Local Warfield Module of Finite Torsion-Free Rank Is the Sum of Two Automorphisms☆

Abstract A well-known result of P. Hill's [1969, Trans. Amer. Math. Soc. 141 , 99–105] says that any endomorphism of a totally projective abelian p -group for any odd prime is the sum of two automorphisms. We will extend this result to local Warfield modules of finite torsion-free rank over odd primes.
Cardiopulmonary exercise testing during follow-up after acute pulmonary embolism

Background Cardiopulmonary exercise testing (CPET) may provide prognostically valuable information during follow-up after pulmonary embolism (PE). Our objective was to investigate the association of patterns and degree of exercise limitation, as assessed by CPET, with clinical, echocardiographic and laboratory abnormalities and quality of life (QoL) after PE. Methods In a prospective cohort study of unselected consecutive all-comers with PE, survivors of the index acute event underwent 3- and 12-month follow-ups, including CPET. We defined cardiopulmonary limitation as ventilatory inefficiency or insufficient cardiocirculatory reserve. Deconditioning was defined as peak O2 uptake (V′O2) <80% with no other abnormality. Results Overall, 396 patients were included. At 3 months, prevalence of cardiopulmonary limitation and deconditioning was 50.1% (34.7% mild/moderate; 15.4% severe) and 12.1%, respectively; at 12 months, it was 44.8% (29.1% mild/moderate; 15.7% severe) and 14.9%, respectively. Cardiopulmonary limitation and its severity were associated with age (OR per decade 2.05, 95% CI 1.65–2.55), history of chronic lung disease (OR 2.72, 95% CI 1.06–6.97), smoking (OR 5.87, 95% CI 2.44–14.15) and intermediate- or high-risk acute PE (OR 4.36, 95% CI 1.92–9.94). Severe cardiopulmonary limitation at 3 months was associated with the prospectively defined, combined clinical-haemodynamic end-point of “post-PE impairment” (OR 6.40, 95% CI 2.35–18.45) and with poor disease-specific and generic health-related QoL. Conclusions Abnormal exercise capacity of cardiopulmonary origin is frequent after PE, being associated with clinical and haemodynamic impairment as well as long-term QoL reduction. CPET can be considered for selected patients with persisting symptoms after acute PE to identify candidates for closer follow-up and possible therapeutic interventions. Cardiopulmonary exercise limitation is frequent after PE and associated with persisting clinical, echocardiographic and laboratory abnormalities as well as worse QoL. CPET may serve as a diagnostic modality for patients with persisting symptoms after PE. https://bit.ly/3SRlEGQ
Application of Chebyshev polynomials to the optimal control of time-varying linear systems

The operational matrix of backward integration for the shifted Chebyshev polynomials is introduced in this study. The general expression of the shifted Chebyshev polynomial approximation for any two arbitrary functions is also presented. A linear time-varying optimal control system with a quadratic performance measure is solved by using the shifted Chebyshev polynomials. Only a small number of Chebyshev polynomials is needed to produce an excellent result, and the outcome is much better than the solution obtained by using the block-pulse function. So, computer memory capacity and computing time can be saved considerably.
Infarct Evolution in Patients with Anterior Circulation Large-Vessel Occlusion Randomized to IV Alteplase and Endovascular Treatment versus Endovascular Treatment Alone

BACKGROUND AND PURPOSE: Infarct evolution after endovascular treatment varies widely among patients with stroke and may be affected by baseline characteristics and procedural outcomes. Moreover, IV alteplase and endovascular treatment may influence the relationship of these factors to infarct evolution. We aimed to assess whether the infarct evolution between baseline and follow-up imaging was different for patients who received IVT and EVT versus EVT alone. MATERIALS AND METHODS: We included patients from the Multicenter Randomized Clinical Trial of Endovascular Treatment for Acute Ischemic Stroke in the Netherlands (MR CLEAN)-NO IV trial with baseline CTP and follow-up imaging. Follow-up infarct volume was segmented on 24-hour or 1-week follow-up DWI or NCCT. Infarct evolution was defined as the follow-up lesion volume: CTP core volume. Substantial infarct growth was defined as an increase in follow-up infarct volume of >10 mL. We assessed whether infarct evolution was different for patients with IV alteplase and endovascular treatment versus endovascular treatment alone and evaluated the association of baseline characteristics and procedural outcomes with infarct evolution using multivariable regression. RESULTS: From 228 patients with CTP results available, 145 patients had follow-up imaging and were included in our analysis. For patients with IV alteplase and endovascular treatment versus endovascular treatment alone, the baseline median CTP core volume was 17 (interquartile range = 4–35) mL versus 11 (interquartile range = 6–24) mL. The median follow-up infarct volume was 13 (interquartile range, 4–48) mL versus 17 (interquartile range = 4–50) mL. Collateral status and occlusion location were negatively associated with substantial infarct growth in patients with and without IV alteplase before endovascular treatment. CONCLUSIONS: No statistically significant difference in infarct evolution was found in directly admitted patients who received IV alteplase and endovascular treatment within 4.5 hours of symptom onset versus patients who underwent endovascular treatment alone. Collateral status and occlusion location may be useful predictors of infarct evolution prognosis in patients eligible for IV alteplase who underwent endovascular treatment.
Application of the three omega thermal conductivity measurement method to a film on a substrate of finite thickness

The three omega thermal conductivity measurement method is analyzed for the case of one or more thin films on a substrate of finite thickness. The analysis is used to obtain the thermal conductivities of SiO2 films on Si substrates and of a chemical vapor deposition (CVD) diamond plate. For the case of the SiO2 films on a Si, we find an apparent thickness dependence of the thermal conductivity of the SiO2 films. However, the data can also be explained by a thickness-independent thermal conductivity and an interfacial thermal resistance. For the case of the CVD diamond plate, the fit of the theory to the experimental data is significantly improved if we assume that an interface layer separates the heater from the diamond plate.
The role of science in a crisis: Talks by political leaders during the COVID-19 pandemic

During the COVID-19 pandemic, science has been prominently featured in institutional communication and political agendas as never before. Governments substantially relied on scientific experts to analyze pandemic trends, develop anti-COVID-19 vaccines and adopt containment strategies. In this paper, we analyze speeches by three political leaders–Boris Johnson (Prime Minister, UK), Sergio Mattarella (President of the Republic, Italy), and Ursula von der Leyen (President, European Commission)–between February 20, 2020, and February 20, 2022, to identify how science was addressed and framed. The results of the quantitative and qualitative exploration of the speeches highlight three main ways in which political leaders view science: a national pride narrative–i.e., science as an instrument and indicator of national pride and international standing of the country; an ethical narrative–i.e., science as an agent of social growth; an integration narrative–i.e., science as a driving force of both European integration and stronger collaboration between knowledge production and industry. The predominant narrative varies in relation to the political leaders’ different institutional contexts and roles.
A Population-Based Study on Injury Risk and Disparities Among Children With ADHD

Objective: Impaired attention and inhibitory control put children with ADHD at potentially high risk of injury—one of the leading causes of disability in the general pediatric population. Existing research has yet to examine this important health risk using nationally representative samples. This population-based study aimed to address this gap. Methods: National estimates of injury occurrences were generated from 66,236 children in the Medical Expenditures Panel Survey 2010–2019 datasets. Multiple logistic regression models further examined the impact of injury type, age, race/ethnicity, sex, parental education, income, marital and insurance status on injury prevalence. Results: Compared to children without ADHD, those with ADHD have significantly higher injury prevalence (OR = 1.20, 95% CI [1.07, 1.33]) across injury types and most sociodemographic subgroups. Conclusions: Children with ADHD are more likely to experience injury. Future research should investigate mechanisms of injury disparities to inform future preventive efforts.