Miracle-dz/UniFAR-FTUs huggingface dataset:
Neural correlates of oral word reading, silent reading comprehension, and cognitive subcomponents

The ability to read is essential for cognitive development. To deepen our understanding of reading acquisition, we explored the neuroanatomical correlates (cortical thickness; CT) of word-reading fluency and sentence comprehension efficiency in Chinese with a group of typically developing children (N = 21; 12 females and 9 males; age range 10.7–12.3 years). Then, we investigated the relationship between the CT of reading-defined regions and the cognitive subcomponents of reading to determine whether our study lends support to the multi-component model. The results demonstrated that children’s performance on oral word reading was positively correlated with CT in the left superior temporal gyrus (LSTG), left inferior temporal gyrus (LITG), left supramarginal gyrus (LSMG) and right superior temporal gyrus (RSTG). Moreover, CT in the LSTG, LSMG and LITG uniquely predicted children’s phonetic representation, phonological awareness, and orthography–phonology mapping skills, respectively. By contrast, children’s performance on sentence-reading comprehension was positively correlated with CT in the left parahippocampus (LPHP) and right calcarine fissure (RV1). As for the subcomponents of reading, CT in the LPHP was exclusively correlated with morphological awareness, whereas CT in the RV1 was correlated with orthography–semantic mapping. Taken together, these findings indicate that the reading network of typically developing children consists of multiple sub-divisions, thus providing neuroanatomical evidence in support of the multi-componential view of reading.
Multitasking During Simulated Car Driving: A Comparison of Young and Older Persons

Human multitasking is typically studied by repeatedly presenting two tasks, either sequentially (task switch paradigms) or overlapping in time (dual-task paradigms). This is different from everyday life, which typically presents an ever-changing sequence of many different tasks. Realistic multitasking therefore requires an ongoing orchestration of task switching and dual-tasking. Here we investigate whether the age-related decay of multitasking, which has been documented with pure task-switch and pure dual-task paradigms, can also be quantified with a more realistic car driving paradigm. 63 young (20–30 years of age) and 61 older (65–75 years of age) participants were tested in an immersive driving simulator. They followed a car that occasionally slowed down and concurrently executed a mixed sequence of loading tasks that differed with respect to their sensory input modality, cognitive requirements and motor output channel. In two control conditions, the car-following or the loading task were administered alone. Older participants drove more slowly, more laterally and more variably than young ones, and this age difference was accentuated in the multitask-condition, particularly if the loading task took participants’ gaze and attention away from the road. In the latter case, 78% of older drivers veered off the road and 15% drove across the median. The corresponding values for young drivers were 40% and 0%, respectively. Our findings indicate that multitasking deteriorates in older age not only in typical laboratory paradigms, but also in paradigms that require orchestration of dual-tasking and task switching. They also indicate that older drivers are at a higher risk of causing an accident when they engage in a task that takes gaze and attention away from the road.
Panax ginseng Polysaccharide Protected H9c2 Cardiomyocyte From Hypoxia/Reoxygenation Injury Through Regulating Mitochondrial Metabolism and RISK Pathway

Background and Objective: Ischemic heart disease (IHD) has been the major issue of public health. Panax ginseng (ginseng) has been verified as an effective traditional Chinese medicines and exerted cardioprotective effect. This study aimed to investigate the polysaccharide fraction of ginseng on hypoxia/reoxygenation (H/R) injury in cardiomyocytes and the underlying mechanisms. Methods: Ginseng was extracted by ethanol and fractionated by high-speed counter current chromatography (HSCCC) and column separation. The cardioprotective effect was evaluated in H9c2 cardiomyocytes underwent H/R treatment. The cell viability, apoptosis and mitochondrial respiration were examined. Results: An acid polysaccharides fraction of ginseng (AP1) was identified the most effective fraction in protecting cardiomyocytes from H/R injury. AP1 restored the mitochondrial function by maintaining mitochondrial membrane potential (MMP), blocking the release of cytochrome C, and increasing the ATP generation and oxygen consumption rate (OCR) of cardiomyocytes. Meanwhile, AP1 induced the expression of glucocorticoid receptor (GR) and estrogen receptor (ER) which further activated reperfusion injury salvage kinase (RISK) pathway. Finally, AP1 increased nitric oxide (NO) production and regulated endothelial function by increasing endothelial NO synthase (eNOS) expression and decreasing inducible NOS (iNOS) expression in H/R injury. Conclusion: The results suggested that AP1 exerted a protective effect in myocardial H/R injury mainly through maintaining myocardial mitochondrial function, thereby inhibiting myocardial H/R caused apoptosis and increasing the expressions of GR and ER, which in turn mediated the activation of RISK pathway and eNOS-dependent mechanism to resist the reperfusion injury.
Zeb1 potentiates genome‐wide gene transcription with Lef1 to promote glioblastoma cell invasion

Glioblastoma is the most common and aggressive brain tumor, with a subpopulation of stem‐like cells thought to mediate its recurring behavior and therapeutic resistance. The epithelial–mesenchymal transition (EMT) inducing factor Zeb1 was linked to tumor initiation, invasion, and resistance to therapy in glioblastoma, but how Zeb1 functions at molecular level and what genes it regulates remain poorly understood. Contrary to the common view that EMT factors act as transcriptional repressors, here we show that genome‐wide binding of Zeb1 associates with both activation and repression of gene expression in glioblastoma stem‐like cells. Transcriptional repression requires direct DNA binding of Zeb1, while indirect recruitment to regulatory regions by the Wnt pathway effector Lef1 results in gene activation, independently of Wnt signaling. Amongst glioblastoma genes activated by Zeb1 are predicted mediators of tumor cell migration and invasion, including the guanine nucleotide exchange factor Prex1, whose elevated expression is predictive of shorter glioblastoma patient survival. Prex1 promotes invasiveness of glioblastoma cells in vivo highlighting the importance of Zeb1/Lef1 gene regulatory mechanisms in gliomagenesis.
Ability to Assent in Pediatric Critical Care Research: A Prospective Environmental Scan of Two Canadian PICUs

Objectives: To determine the number of patients considered not appropriate to approach for assent within the first 24 hours of PICU admission. Design: Exploratory prospective 1-month environmental scan. Setting: Two tertiary Canadian PICUs. Patients: Ninety patients age newborn to 17 years old admitted to the PICU during September 2016 (Site 1) or May 2017 (Site 2). Interventions: None. Measurements and Main Results: At PICU admission, 81% of patients were deemed not appropriate to approach for assent most commonly due to age, influence of psychotropic medications, and/or mechanical ventilation. At PICU discharge, 74% of patients were considered not appropriate to approach, most commonly due to age and/or developmental delay. There was moderate to good agreement between the research team and care team assessments of appropriateness for assent. Only 8% of patients considered not approachable at admission become appropriate to approach for assent by PICU discharge. Conclusions: Very few patients were considered approachable for assent during the first 24 hours of PICU admission. Those who were considered appropriate to approach were less ill, spent less time in PICU, and were unlikely to be considered for enrollment in pediatric critical care research.
Clinical use of submaximal treadmill exercise testing and assessments of cardiac biomarkers NT-proBNP and cTnI in dogs with presymptomatic mitral regurgitation

Exercise intolerance is the first symptom of heart disease. Yet an objective and standardised method in canine cardiology to assess exercise capacity in a clinical setting is lacking. In contrast, exercise testing is a powerful diagnostic tool in humans, providing valuable information on prognosis and impact of therapeutic intervention. To investigate whether an exercise test reveals differences between dogs with early stage mitral regurgitation (MR) and dogs without cardiac disease, 12 healthy beagles (healthy group, HG) and 12 dogs with presymptomatic MR (CHIEF B1 / B2, patient group, PG) underwent a six-stage submaximal exercise test (ET) on a motorised treadmill. They trotted in their individual comfort speed for three minutes per stage, first without incline, afterwards increasing it by 4% for every subsequent stage. Blood samples were taken at rest and during two 3-minute breaks in the course of the test. Further samples were taken after the completion of the exercise test and again after a 3-hour recovery period. Measured parameters included heart rate, lactate and the cardiac biomarkers N-terminal pro-B-Type natriuretic peptide and cardiac Troponin I. The test was performed again under the same conditions in the same dogs three weeks after the first trial to evaluate individual repeatability. Cardiac biomarkers increased significantly in both HG and PG in the course of the test. The increase was more pronounced in CHIEF B1 / B2 dogs than in the HG. N-terminal pro-B-Type natriuretic peptide increased from 435 ± 195 to 523 ± 239 pmol/L (HG) and from 690 to 815 pmol/L (PG). cTnI increased from 0.020 to 0.024 ng/mL (HG) and from 0.06 to 0.08 ng/ml (PG). The present study provides a method to assess exercise-induced changes in cardiac biomarkers under clinical conditions. The increase of NT-proBNP and cTnI is more pronounced in dogs with early-stage MR than in healthy dogs. Results indicate that measuring the parameters before and after exercise is adequate and taking blood samples between the different stages of the ET does not provide additional information. Also, stress echocardiography was inconclusive. It can be concluded that exercise testing, especially in combination with measuring cardiac biomarkers, could be a helpful diagnostic tool in canine cardiology.
Exposure to Community Violence as a New Adverse Childhood Experience Category: Promising Results and Future Considerations

Research links high youth exposure to community violence (ECV) with negative health consequences, and the World Health Organization recommends ECV as a new adverse childhood experience (ACE) category. The current study is among the first to include ECV within the ACE categories, examining ACEs and behavioral health (BH) service usage, using a population-based adult sample. Results reveal ECV and ACE associations in the expected direction. Respondents reporting ECV before age 18 had higher ACE scores than those without ECV. Results demonstrate ECV's predictive power for later BH needs and confirm its utility as a new ACE category. Practice implications include attention to ECV among adult populations and mitigating long-term costs through early intervention and prevention.
Systematic review and guide to management of core and psychiatric symptoms in youth with autism

Evidence‐based guidance of clinical decision‐making for the management of Autism Spectrum Disorder (ASD) is lacking, particularly for co‐occurring psychiatric symptoms. This review evaluates treatment evidence for six common symptom targets in children/adolescents with ASD and provides a resource to facilitate application of the evidence to clinical practice.
Depression in chronic pain: might opioids be responsible?

Each year, millions of patients receive prescription opioids in an effort to reduce the suffering associated with chronic pain. Although the effectiveness of long-term opioid therapy has never been convincingly established, several of its more serious consequences (including addiction, overdose, and death) are well known and have increased in tandem with the more liberal prescribing of the past 2 decades. However, chronic opioid prescribing on a large scale has also revealed some of the drugs’ subtler harms. Opioids are clearly associated with an increased risk of falls, fractures, and motor vehicle collisions; they suppress testosterone in men and can lead to infertility in women; and in some patients, they can paradoxically worsen pain, particularly at high doses. Converging lines of evidence now suggest that depression—a common comorbidity in the setting of chronic pain—may in some patients represent an unrecognized yet potentially reversible harm of opioid therapy. This possibility bears directly on treatment decisions and the well-being of millions of patients living with chronic pain.We briefly review the emerging evidence suggesting that opioid therapy may be a component cause of depression, and show that the association satisfies many classic elements of causal inference.
A review on the Idylla platform: towards the assessment of actionable genomic alterations in one day

Cancer still represents a major cause of death in the world. In the last decades, a better understanding of the molecular bases of cancer initiation, progression and antitumour immunity response escape has led to the development of new therapeutic strategies. Indeed, targeted treatments against oncogenic proteins and immune-checkpoint inhibitors have considerably improved quality of life and treatment outcomes of patients with cancer. Thus, assessment of predictive biomarker is crucial. According to the US Food and Drug Administration, a companion diagnostic assay, which provides essential information for the safe and effective use of a corresponding drug, is a unique medical device. Conversely, in the European Union the same biomarker can be analysed by using different diagnostic platforms, with different advantages and drawbacks. Nevertheless, any commercially available diagnostic assay needs to achieve validation, for approval by the European Community for in vitro diagnostic use (CE-IVD). Although the next-generation sequencing (NGS) of even whole exomes or genomes is today feasible in expert centres, currently only limited pieces of genomic information are clinically relevant for the therapeutic management of patients with advanced cancers. Indeed, besides clinical trials and experimental protocols, the list of predictive actionable genomic biomarkers is quite short to date. Relevant examples include in colorectal cancer mutations of KRAS and NRAS ; in lung cancer, mutations of EGFR and rearrangements of ALK and ROS1 ; and in melanoma BRAF and NRAS mutations.1–8 Reflecting the requirements of expensive equipments, experience and skilled personnel, these mutational assays are often centralised in reference laboratories. The longer interval of time between test prescription and result delivery may delay the treatment of patients with advanced cancers, some of them suffering from acute deterioration and needing rapid therapeutic decisions. The Idylla system (Biocartis, Mechelen, Belgium) can be easily implemented in pathology laboratories to diagnose quickly and simply oncogenic mutations.9–26 This …
Pre-harvest Sprouting and Grain Dormancy in Sorghum bicolor: What Have We Learned?

The possibility of obtaining sorghum grains with quality to match the standards for a diversity of end-uses is frequently hampered by the susceptibility to pre-harvest sprouting (PHS) displayed by many elite genotypes. For these reasons, obtaining resistance to PHS is considered in sorghum breeding programs, particularly when the crop is expected to approach harvest maturity under rainy or damp conditions prevalence. As in other cereals, the primary cause for sprouting susceptibility is a low dormancy prior to crop harvest; in consequence, most research has focused in understanding the mechanisms through which the duration of dormancy is differentially controlled in genotypes with contrasting sprouting behavior. With this aim two tannin-less, red-grained inbred lines were used as a model system: IS9530 (sprouting resistant) and Redland B2 (sprouting susceptible). Redland B2 grains are able to germinate well before reaching physiological maturity (PM) while IS9530 ones can start to germinate at 40–45 days after pollination, well after PM. Results show that the anticipated dormancy loss displayed by Redland B2 grains is related reduced embryo sensitivity to abscisic acid (ABA) and increased levels of GA upon imbibition. In turn, transcriptional data showed that ABA signal transduction is impaired in Redland B2, which appears to have an impact on GA catabolism, thus affecting the overall GA/ABA balance that regulates germination. QTL analyses were conducted to test whether previous candidate genes were located in a dormancy QTL, but also to identify new genes involved in dormancy. These analyses yielded several dormancy QTL and one of them located in chromosome 9 (qGI-9) was consistently detected even across environments. Fine mapping is already in progress to narrow down the number of candidate genes in qGI-9.
Evidence for the Detection of Subclinical Retinal Involvement in Systemic Lupus Erythematosus and Sjögren Syndrome: A Potential Association with Therapies

Background: Retinal involvement in systemic lupus erythematosus (SLE) and Sjögren syndrome (SS) may be subclinical and thus underdiagnosed. Objectives: We aimed at evaluating morphological and functional visual abnormalities in a cohort of SLE and SS patients in the absence of an overt clinical visual impairment. We also investigated potential associations between retinal disorders and disease activity, organ involvement, and treatment with steroid and/or hydroxychloroquine. Methods: The study comprised 42 SLE and 36 primary SS patients and 76 healthy controls (HC). Ophthalmological examination, standard automated perimetry, spectral-domain optical coherence tomography, and fundus perimetry were performed. Results: Retinal thickness of the posterior pole was not different between SLE and HC groups, but it was reduced in the SS group compared with both the HC and the SLE group. In SLE and SS patients, mean defect and pattern standard deviation by standard automated perimetry were higher than in HC. Visual field index values were lower in both SLE and SS patients than in HC. SLE patients with nephritis displayed increased mean defect and pattern standard deviation and reduced visual field index values compared to patients without nephritis. In SLE and SS patients, fundus perimetry differential sensitivity was reduced, and mean defect values were higher than in HC. Disturbances in fundus perimetry in the SLE group were more prevalent in steroid-naïve patients and in SS patients who received a cumulative hydroxychloroquine dose > 1,000 g. Conclusions: Functional eye impairment was demonstrated in SLE patients, possibly associated with kidney involvement. In SLE, corticosteroids might exert a protective role. Morphological alterations and functional impairment were detected in SS patients, which may be linked to hydroxychloroquine toxicity.
A Bcl-2 Associated Athanogene (bagA) Modulates Sexual Development and Secondary Metabolism in the Filamentous Fungus Aspergillus nidulans

The Bcl-2 associated athanogene (Bag) family is a multifunctional group of proteins distinguished by a conserved region known as the Bag domain (BD). Herein, we discuss the discovery and characterization of a Bag protein in the model genetic fungus Aspergillus nidulans, we designated BagA. BagA shares striking similarities in 3D structure, domain organization, amino acid properties, and Hsp70 binding surfaces to animal and plant Bags. While Hsp70 binding is a common feature of Bag proteins, our experimental evidence shows that BagA does not cooperate with A. nidulans Hsp70s, suggesting this association may not be a universal feature of Bag proteins. Gene expression of bagA was strongly induced during sexual development suggesting a role in developmental processes. Accordingly, the deletion of bagA (ΔbagA) negatively impacted sexual development, while its overexpression resulted in constitutive induction of sexual fruiting bodies and spores. Asexual and sexual development was linked to secondary metabolism in A. nidulans. Our data show that the deletion of bagA also provoked an altered secondary metabolite (SM) profile in both sexual and vegetative growth phases. Indeed, LC-MS analysis showed a significant enrichment of SMs in ΔbagA, including novel metabolites not produced by wild type strain. Enrichment of SMs in ΔbagA strain is particularly intriguing and suggest that altering cellular homeostasis can be used as a provocative strategy to activate cryptic metabolites and uncover novel bioactive compounds. Overall, our results indicate that Bag proteins in filamentous fungi share developmental regulatory roles with their animal and plant counterparts. We also show a potentially unique role for BagA in modulating secondary metabolism in A. nidulans. To our knowledge, this study provides a first insight into Bag function in filamentous fungi.
University of Birmingham Glucocorticoids and bone: consequences of endogenous and exogenous excess and replacement therapy

35 Osteoporosis associated with long-term glucocorticoid therapy remains a common and serious bone 36 disease. In addition, in recent years it has become clear that more subtle states of endogenous 37 glucocorticoid excess may have a major impact on bone health. Adverse effects can be seen with 38 mild systemic glucocorticoid excess but there is also evidence of tissue-specific regulation of 39 glucocorticoid action within bone as a mechanism of disease. This review article will examine a) the 40 role of endogenous glucocorticoids in normal bone physiology, b) the skeletal effects of endogenous 41 glucocorticoid excess in the context of endocrine conditions such as Cushing’s disease and 42 autonomous cortisol secretion (subclinical Cushing’s syndrome), and c) the actions of therapeutic 43 (exogenous) glucocorticoids on bone. We will review the extent to which the effect of 44 glucocorticoids on bone is influenced by variations in tissue metabolising enzymes and 45 glucocorticoid receptor expression and sensitivity. We will consider how the effects of therapeutic 46 glucocorticoids on bone are complicated by the effects of the underlying inflammatory disease being 47 treated. We will also examine the impact that glucocorticoid replacement regimens have on bone in 48 the context of primary and secondary adrenal insufficiency. 49