Miracle-dz/UniFAR-FTUs huggingface dataset:
Targeted regulation of TAK1 counteracts dystrophinopathy in a DMD mouse model

Muscular dystrophies make up a group of genetic neuromuscular disorders that involve severe muscle wasting. TGF-β–activated kinase 1 (TAK1) is an important signaling protein that regulates cell survival, growth, and inflammation. TAK1 has been recently found to promote myofiber growth in the skeletal muscle of adult mice. However, the role of TAK1 in muscle diseases remains poorly understood. In the present study, we have investigated how TAK1 affects the progression of dystrophic phenotype in the mdx mouse model of Duchenne muscular dystrophy (DMD). TAK1 is highly activated in the dystrophic muscle of mdx mice during the peak necrotic phase. While targeted inducible inactivation of TAK1 inhibits myofiber injury in young mdx mice, it results in reduced muscle mass and contractile function. TAK1 inactivation also causes loss of muscle mass in adult mdx mice. By contrast, forced activation of TAK1 through overexpression of TAK1 and TAB1 induces myofiber growth without having any deleterious effect on muscle histopathology. Collectively, our results suggest that TAK1 is a positive regulator of skeletal muscle mass and that targeted regulation of TAK1 can suppress myonecrosis and ameliorate disease progression in DMD.
Effect of Mean Entropy on Eigenmodes in Annular Duct with Swirling Flow

(Abstract) The effect of non-uniform mean entropy on the wave modes in a straight annular duct with mean swirling flow is considered. This is representative in turbomachinery applications such as aeroengine where variations in mean entropy could be significant. Normal mode analysis of the unsteady motion by a spectral collocation technique is described and shows that the eigenmodes are characterized as acoustic modes (nearly- sonic or sonic) and rotational modes (nearly-convected or purely-convected). In order to validate present approach the numerical results are first compared with analytical solution for uniform axial flow case and with the previous results for the mean swirling flow cases including uniform and non-uniform mean entropy. Afterwards, the steady mean flow parameters, the unsteady eigenmodes spectra, and the axial unsteady pressure distributions for the first five acoustic modes are addressed to consider the effect of the mean entropy gradient on the cut-on/cut-off characteristics of the acoustic modes. Nomenclature
Functional Connectivity From Disease Epicenters in Frontotemporal Dementia

Background and Objectives MRI connectomics is an ideal tool to test a network-based model of pathologic propagation from a disease epicenter in neurodegenerative disorders. In this study, we used a novel graph theory–based MRI paradigm to explore functional connectivity reorganization, discerning between direct and indirect connections from disease epicenters, and its relationship with neurodegeneration across clinical presentations of the frontotemporal dementia (FTD) spectrum, including behavioral variant of FTD (bvFTD), nonfluent variant of primary progressive aphasia (nfvPPA), and semantic variant of primary progressive aphasia (svPPA). Methods In this observational cross-sectional study, disease epicenters were defined as the peaks of atrophy of a cohort of patients with high confidence of frontotemporal lobar degeneration pathology (Mayo Clinic). These were used as seed regions for stepwise functional connectivity (SFC) analyses in an independent (Milan) set of patients with FTD to assess connectivity in regions directly and indirectly connected to the epicenters. Correlations between SFC architecture in healthy conditions and atrophy patterns in patients with FTD were also tested. Results As defined by comparing the 42 Mayo Clinic patients with 15 controls, disease epicenters were the left anterior insula for bvFTD, left supplementary motor area for nfvPPA, and left inferior temporal gyrus (ITG) for svPPA. Compared with 94 age-matched controls, patients with bvFTD (n = 64) and nfvPPA (n = 34) of the Milan cohort showed widespread decreased SFC in bilateral cortical regions with direct/indirect connections with epicenters and increased SFC either in directly connected regions, physically close to the respective seed region, or in more distant cortical/cerebellar areas with indirect connections. Across all link steps, svPPA (n = 36) showed SFC decrease mostly within the temporal lobes, with co-occurrent SFC increase in cerebellar regions at indirect link steps. The average stepwise topological distance from the left ITG in a reference group of 50 young healthy controls correlated with regional gray matter volume in svPPA, consistent with network-based degeneration. Discussion Our findings demonstrate that each FTD syndrome is associated with a characteristic interplay of decreased and increased functional connectivity with the disease epicenter, affecting both direct and indirect connections. SFC revealed novel insights regarding the topology of functional disconnection across FTD syndromes, holding the promise to be used to model disease progression in future longitudinal studies.
The Epidemiology of Takayasu Arteritis in Rio de Janeiro, Brazil

Objective Few population-based studies for Takayasu arteritis (TAK) have been performed, and Latin America prevalence/incidence data are unavailable. We aimed to understand TAK epidemiology in Rio de Janeiro City in 2020 (i.e., 6,747,815 inhabitants). Methods This was a cross-sectional fieldwork study where physicians who regularly followed TAK patients in public or private practices from Rio de Janeiro were invited to complete a REDCap survey. Patients should fulfill internationally accepted criteria for TAK and be living in the city. The 2020 prevalence was calculated as cases per 1,000,000 inhabitants (106). National government databases were analyzed for comparative prevalence assessment. The incidence rate was estimated using retrospective sections of cases diagnosed between 2010 and 2019; relative incidence risk was assessed by Poisson regression models with robust variance. Results Between May 2020 and May 2021, 114 patients were analyzed. Ninety-seven (85.1%) were female, and the most frequent races were White (44.7%), Mestizo (33.3%), and Black (16.7%). Takayasu arteritis 2020 prevalence was 16.9 cases/106 (95% confidence interval [CI], 14.1–20.3 cases/106); female patients and Black Brazilians had higher prevalence rates at 27.0 (95% CI, 22.2–33.3) and 25.1 cases/106 (95% CI, 16.1–39.3 cases/106), respectively. Government databases' analyses generated a lower prevalence (7.26 cases/106; 95% CI, 5.49–9.60 cases/106). The 2010–2019 mean incidence rate was 0.94 cases/106 per year (95% CI, 0.73–1.21 cases/106). Female patients had a higher risk than male patients of having TAK between 2010 and 2019 (relative risk, 2.70; 95% CI, 1.59–4.55; p < 0.0001). Conclusion In the largest population-based fieldwork to date and the first Latin American study on TAK prevalence, Rio de Janeiro City in 2020 showed an intermediate prevalence between Europe and Asia. Female patients and Black Brazilians were more affected than the general population.
INEQUALITY OF EDUCATIONAL OUTCOMES: INTERNATIONAL

This paper examines the relation between measures of the within-country inequality of student scores on international academic tests and the average level of scores across countries, using the PISA mathematics tests over 2000-2009. It finds that average test scores are higher in countries with lower inequality in scores – a virtuous efficiency-equity relation in test performance – and that family background factors are differently associated with student test performance across countries, but display little impact on the countrywide dispersion of test scores.
Blood transcriptome sequencing identifies biomarkers able to track disease stages in spinocerebellar ataxia type 3.

Transcriptional dysregulation has been described in spinocerebellar ataxia type 3/Machado-Joseph disease (SCA3/MJD), an autosomal dominant ataxia caused by a polyglutamine expansion in the ataxin-3 protein. As ataxin-3 is ubiquitously expressed, transcriptional alterations in blood may reflect early changes that start before clinical onset and might serve as peripheral biomarkers in clinical and research settings. Our goal was to describe enriched pathways and report dysregulated genes which can track disease onset, severity, or progression in carriers of the ATXN3 mutation (pre-ataxic subjects and patients). Global dysregulation patterns were identified by RNA sequencing of blood samples from 40 carriers of ATXN3 mutation and 20 controls and further compared with transcriptomic data from post-mortem cerebellum samples of MJD patients and controls. Ten genes - ABCA1, CEP72, PTGDS, SAFB2, SFSWAP, CCDC88C, SH2B1, LTBP4, MEG3 and TSPOAP1 - whose expression in blood was altered in the pre-ataxic stage and simultaneously, correlated with ataxia severity in the overt disease stage, were analysed by quantitative real-time PCR in blood samples from an independent set of 170 SCA3/MJD subjects and 57 controls. Pathway enrichment analysis indicated the Gαi signalling and the oestrogen receptor signalling to be similarly affected in blood and cerebellum. SAFB2, SFSWAP and LTBP4 were consistently dysregulated in pre-ataxic subjects compared to controls, displaying a combined discriminatory ability of 79%. In patients, ataxia severity was associated with higher levels of MEG3 and TSPOAP1. We propose expression levels of SAFB2, SFSWAP and LTBP4 as well as MEG3 and TSPOAP1 as stratification markers of SCA3/MJD progression, deserving further validation in longitudinal studies and in independent cohorts.
Modelling the Volatility-Return Trade-Off When Volatility May Be Nonstationary

In this paper a new GARCH–M type model, denoted the GARCH-AR, is proposed. In particular, it is shown that it is possible to generate a volatility-return trade-off in a regression model simply by introducing dynamics in the standardized disturbance process. Importantly, the volatility in the GARCH-AR model enters the return function in terms of relative volatility, implying that the risk term can be stationary even if the volatility process is nonstationary. We provide a complete characterization of the stationarity properties of the GARCH-AR process by generalizing the results of Bougerol and Picard (1992b). Furthermore, allowing for nonstationary volatility, the asymptotic properties of the estimated parameters by quasi-maximum likelihood in the GARCH-AR process are established. Finally, we stress the importance of being able to choose correctly between AR-GARCH and GARCH-AR processes: First, it is shown, by a small simulation study, that the estimators for the parameters in an ARGARCH model will be seriously inconsistent if the data generating process actually is a GARCH-AR process. Second, we provide an LM test for neglected GARCH-AR effects and discuss its finite sample size properties. Third, we provide an empirical illustration showing the empirical relevance of the GARCH-AR model based on modelling a wide range of leading US stock return series.
Instrumental Variables Regression with Weak Instruments

This paper develops asymptotic distribution theory for instrumental variable regression when the partial correlation between the instruments and a single included endogenous variable is weak, here modeled as local to zero. Asymptotic representations are provided for various instrumental variable statistics, including the two-stage least squares (TSLS) and limited information maximum- likelihood (LIML) estimators and their t-statistics. The asymptotic distributions are found to provide good approximations to sampling distributions with just 20 observations per instrument. Even in large samples, TSLS can be badly biased, but LIML is, in many cases, approximately median unbiased. The theory suggests concrete quantitative guidelines for applied work. These guidelines help to interpret Angrist and Krueger's (1991) estimates of the returns to education: whereas TSLS estimates with many instruments approach the OLS estimate of 6%, the more reliable LIML and TSLS estimates with fewer instruments fall between 8% and 10%, with a typical confidence interval of (6%, 14%).
COVID-19 in immunocompromised children and adolescents

Since coronavirus disease 2019 (COVID-19) became a global pandemic, concerns have arisen regarding the risks of COVID-19 in immunocompromised children and adolescents. Here we aimed to evaluate the clinical outcomes and risks of severe COVID-19 in immunocompromised pediatric patients. Previous studies reported that most children and adolescents receiving immunosuppressive medications have clinical presentations and favorable outcomes similar to those of the general pediatric population. Treatments and access to health services should not be interrupted in these populations, and continuous monitoring of the potential impact of variant strains on the risk of immunocompromised pediatric patients is warranted.
Antiseizure Medication Use During Pregnancy and Neonatal Growth Outcomes: A Systematic Review and Meta-Analysis.

AIM We aimed to systematically synthesize the current published literature on neonatal growth outcomes associated with antiseizure medications (ASMs) use during pregnancy. METHODS We searched seven databases, from inception to March 23rd, 2022. We investigated small for gestational age (SGA) and low birth weight (LBW) as primary outcomes and birth weight, birth height, cephalization index and head circumference as secondary outcomes. The primary analysis included pregnant people exposed to any ASM compared with unexposed pregnant people. Subgroup analysis included ASMs class analysis, within epilepsy group analysis and polytherapy compared to monotherapy. RESULTS We screened 15,720 citations and included 65 studies in the review. Exposed pregnant people had a significantly increased risk of SGA relative risk (RR) 1.33 (95%CI 1.18 to 1.50, I2 74%), LBW RR 1.54 (95%CI 1.33 to 1.77, I2 67%), and decreased birth weight with a mean difference (MD) of -118.87 (95%CI -161.03 to -76.71, I2 42%) g. A non-significant risk change in birth height and head circumference was observed. In subgroup analysis, ASM polytherapy, within epilepsy and ASMs class analysis were also associated with an increased risk of SGA and LBW. CONCLUSION This meta-analysis demonstrates that pregnant people exposed to ASMs have a significantly increased risk of adverse fetal growth outcomes including SGA and LBW and decreased birth weight compared to unexposed pregnant people. Polytherapy was associated with higher risks compared to monotherapy. Additional studies are warranted on specific ASMs risks.
Antibacterial and Anti-Biofilm Activities of Microbial Synthesized Silver and Magnetic Iron Oxide Nanoparticles Against Pseudomonas aeruginosa

Pseudomonas aeruginosa is a human bacterial pathogen causing devastating diseases and equipped with various virulence factors like biofilm formation. Common antibiotic treatment has limited efficacy for the P. aeruginosa present in biofilms because of the increased resistance. In this study, we focused our attention on the antibacterial and anti-biofilm activities of various microbial synthesized silver (nano-Ag) and magnetic iron oxide (nano-Fe3O4) nanoparticles against clinical isolates of P. aeruginosa that displayed ceftazidime resistance. The nano-Ag and nano-Fe3O4 represented great antibacterial properties. Nano-Ag and nano-Fe3O4 exhibited a reduction in the biofilm formation by P. aeruginosa reference strain as determined by crystal violet and XTT assays and light microscopy method. Among all, nano-Ag-2 and 7 owing to inherent attributes and mechanisms of resistance in the bacterial biofilm, exhibited anti-biofilm efficacy against ceftazidime resistance clinical isolate of P. aeruginosa. Moreover, nano-Ag and nano-Fe3O4 changed the relative expression of biofilm-associated genes, PELA and PSLA in a concentration dependent manner by P. aeruginosa reference strain. As revealed by qRT-PCR, the expression levels of biofilm-associated genes were downregulated in P. aeruginosa biofilms treated with nano-Ag, while selected biofilm-associated genes were low expressed under treated with nano-Fe3O4. Results of the study demonstrate the potential of microbial synthesized nano-Ag-2 and 7 to act as anti-biofilm agents against ceftazidime resistance clinical isolate of P. aeruginosa. Molecular targeting of biofilm-associated genes by nano-Ag and nano-Fe3O4 may be candidate for new therapeutics against P. aeruginosa diseases.
Trajectories of Emotion Recognition Training in Virtual Reality and Predictors of Improvement for People with a Psychotic Disorder

Meta-analyses have found that social cognition training (SCT) has large effects on the emotion recognition ability of people with a psychotic disorder. Virtual reality (VR) could be a promising tool for delivering SCT. Presently, it is unknown how improvements in emotion recognition develop during (VR-)SCT, which factors impact improvement, and how improvements in VR relate to improvement outside VR. Data were extracted from task logs from a pilot study and randomized controlled trials on VR-SCT (n = 55). Using mixed-effects generalized linear models, we examined the: (a) effect of treatment session (1–5) on VR accuracy and VR response time for correct answers; (b) main effects and moderation of participant and treatment characteristics on VR accuracy; and (c) the association between baseline performance on the Ekman 60 Faces task and accuracy in VR, and the interaction of Ekman 60 Faces change scores (i.e., post-treatment − baseline) with treatment session. Accounting for the task difficulty level and the type of presented emotion, participants became more accurate at the VR task (b = 0.20, p < 0.001) and faster (b = −0.10, p < 0.001) at providing correct answers as treatment sessions progressed. Overall emotion recognition accuracy in VR decreased with age (b = −0.34, p = 0.009); however, no significant interactions between any of the moderator variables and treatment session were found. An association between baseline Ekman 60 Faces and VR accuracy was found (b = 0.04, p = 0.006), but no significant interaction between difference scores and treatment session. Emotion recognition accuracy improved during VR-SCT, but improvements in VR may not generalize to non-VR tasks and daily life.
Advances in multi-modality imaging for constrictive pericarditis and pericardial inflammation: role of imaging-guided therapy

ABSTRACT Introduction Constrictive pericarditis (CP) can result from uncontrolled inflammation of the pericardium. This can be due to various etiologies. CP can lead to both left- and right-sided heart failure with associated poor quality of life, so early recognition is key. The evolving role of multimodality cardiac imaging allows for earlier diagnosis and facilitates management to help mitigate this adverse outcome. Areas covered This review discusses the pathophysiology of constrictive pericarditis, chronic inflammation and autoimmune etiologies, clinical presentation of CP, and advances in multimodality cardiac imaging for diagnosis and management. Echocardiography and cardiac magnetic resonance (CMR) imaging remain cornerstone modalities to evaluate this condition, whereas additional imaging modalities such as computed tomography and FDG-positron emission tomography can provide complementary information. Expert opinion Advances in multimodality imaging allow for a more precision diagnosis of constrictive pericarditis. There has been a paradigm shift in pericardial disease management with advances in multimodality imaging, especially CMR, to detect subacute and chronic inflammation. This has enabled imaging-guided therapy (IGT) to both help prevent and potentially reverse established constrictive pericarditis.
Astrocytic aerobic glycolysis provides lactate to support neuronal oxidative metabolism in the hippocampus

Under physiological conditions, the energetic demand of the brain is met by glucose oxidation. However, ample evidence suggests that lactate produced by astrocytes through aerobic glycolysis may also be an oxidative fuel, highlighting the metabolic compartmentalization between neural cells. Herein, we investigate the roles of glucose and lactate in oxidative metabolism in hippocampal slices, a model that preserves neuron–glia interactions. To this purpose, we used high‐resolution respirometry to measure oxygen consumption (O2 flux) at the whole tissue level and amperometric lactate microbiosensors to evaluate the concentration dynamics of extracellular lactate. We found that lactate is produced from glucose and transported to the extracellular space by neural cells in hippocampal tissue. Under resting conditions, endogenous lactate was used by neurons to support oxidative metabolism, which was boosted by exogenously added lactate even in the presence of excess glucose. Depolarization of hippocampal tissue with high K+ significantly increased the rate of oxidative phosphorylation, which was accompanied by a transient decrease in extracellular lactate concentration. Both effects were reverted by inhibition of the neuronal lactate transporter, monocarboxylate transporters 2 (MCT2), supporting the concept of an inward flux of lactate to neurons to fuel oxidative metabolism. We conclude that astrocytes are the main source of extracellular lactate which is used by neurons to fuel oxidative metabolism, both under resting and stimulated conditions.
Optical Design and Fabrication of a Large Telephoto Zoom Lens with Fixed f/2.8 and Light Autofocus Lens

Compact system cameras (CSCs) are commonly used nowadays and feature enhanced video functions and thin yet light interchangeable lenses. They differ from digital single-lens reflex (DSLR) cameras in their lack of mirror boxes. CSCs, however, have autofocus (AF) speeds lower than those of conventional DSLRs, requiring weight reduction of their AF groups. To ensure the marketability of large telephoto zoom lenses with fixed f/2.8 regardless of field angle variation, in particular, light weight AF groups are essential. In this paper, we introduce a paraxial optical design method and present a new, large, telephoto zoom lens with f/2.8 regardless of the field angle variation, plus a lightweight AF group consisting of only one lens. Using the basic paraxial optical design and optimization methods, we fabricated a new and lighter zoom lens system, including a single-lens, lightweight AF group with almost the same performance.