Miracle-dz/UniFAR-FTUs huggingface dataset:
Neural and behavioral correlates of expectancy violations in attention-deficit hyperactivity disorder.

BACKGROUND Attention deficit hyperactivity disorder (ADHD) is a prevalent neuropsychiatric disorder in childhood with established problems in cognitive control and associated fronto-striatal circuitry. More recently, fronto-cerebellar circuits have been implicated in this disorder. Both of these circuits are important in predicting the occurrence and timing of behaviorally relevant events and in detecting violations of these predictions. Therefore, we hypothesized that the ability to predict the occurrence of frequent events would be compromised in ADHD, as well as the ability to adapt behavior when expectancy was violated. METHODS We used rapid, mixed-trial, event-related functional magnetic resonance imaging (fMRI) to examine cognitive and neural processes in two independent samples of children and adolescents with ADHD and matched controls. Subjects performed a variation of a go-no/go task where the predictability of stimulus identity (what) and timing (when) was manipulated. RESULTS Behaviorally, children and adolescents with ADHD had increased variability in reaction times, and decreased benefit in reaction time when events were predictable. Differences in accuracy between groups were most reliable for temporally unpredictable trials. Functional imaging results from both samples showed that relative to the control children and adolescents, individuals with ADHD had diminished cerebellar activity to violations of stimulus timing and diminished ventral prefrontal and anterior cingulate activity to violations in stimulus timing and identity. CONCLUSIONS These findings are consistent with the view that disruptive behaviors in inappropriate contexts, a major criterion in diagnosing ADHD, may be related to an impaired ability to predict temporal and contextual cues in the environment, thus hindering the ability to alter behavior when they change. This ability requires intact fronto-cerebellar, as well as fronto-striatal circuitry.
Environmental Toxicology and Chemistry

Human activities have increased the release of selenium (Se) to aquatic environments, but information about the trophic transfer dynamics of Se in Canadian boreal lake systems is limited. In the present study, Se was added as selenite to limnocorrals (2‐m‐diameter, 3000‐L in situ enclosures) in a boreal lake in northwestern Ontario to reach nominal concentrations of 1 and 10 μg Se/L in triplicate each for 77 d, and 3 additional limnocorrals were controls with no Se added. Total Se concentrations were determined in water, sediment, periphyton, benthic macroinvertebrates, zooplankton, and reproductively mature female fathead minnows (Pimephales promelas; added on day 33) collected throughout (and at the end of) the exposure period. Mean measured water Se concentrations in the control, 1‐, and 10‐μg/L treatments were 0.12, 1.0, and 8.9 μg/L. At the end of exposure (day 77), enrichment functions ranged from 7772 L/kg dry mass in the 8.9‐μg/L treatment to 23 495 L/kg dry mass in the 0.12‐μg/L treatment, and trophic transfer factors for benthic macroinvertebrates ranged from 0.49 for Gammaridae to 2.3 for Chironomidae. Selenium accumulated in fathead minnow ovaries to concentrations near or above the current US Environmental Protection Agency criterion (15.1 μg/g dry mass for fish ovary/egg) in the 1.0‐ and 8.9‐μg/L treatments, suggesting that, depending on aqueous Se speciation, such exposures have the potential to cause Se accumulation in fish to levels of concern in cold‐water, boreal lake systems. Environ Toxicol Chem 2019;38:1954–1966. © 2019 SETAC
Continuous, objective measurement of physical activity during chemotherapy for breast cancer: the Activity in Treatment pilot study.

Despite many potential benefits of physical activity during and after breast cancer treatment, activity levels typically decline from pre- to posttreatment. Most previous research has relied on self-reported activity. The purpose of this study were to assess patterns of daily, to objectively measured physical activity throughout chemotherapy for breast cancer, and to identify predictors of physical activity patterns. Participants were given a Fitbit before starting chemotherapy and asked to wear it throughout chemotherapy. Restricted cubic splines assessed nonlinear patterns of Fitbit measured total physical activity (TPA) and moderate-to-vigorous physical activity (MVPA) throughout the duration of chemotherapy (mean = 17 weeks, standard deviation [SD] = 6.3). Mixed-effects regression models assessed the rate of physical activity decline. Regressions of subject-level random slope assessed predictors of the rate of physical activity decline on participant and cancer characteristics and self-reported physical and cognitive functioning. Participants (n = 32) were on average 50 years old; the majority had stage II breast cancer. MVPA declined linearly at a mean rate of 1.4 min/day (p = .002) for every 10% of chemotherapy completed, whereas TPA declined linearly at an average rate of 13.4 min/day (p = .0007) for every 10% of chemotherapy completed, until around halfway through chemotherapy, when activity rates leveled off. HER+ receptor status was associated with a greater rate of MVPA decline, β = 13.3, p = . 04. This novel study of objectively measured daily MVPA throughout chemotherapy showed that most reductions in activity occurred during the first half of a course of chemotherapy. Targeting this early period of chemotherapy may be important for preventing declines in activity levels throughout chemotherapy.
Sequential interleukin 3 and granulocyte‐macrophage–colony stimulating factor therapy in patients with bone marrow failure with long‐term follow‐up of responses

Interleukin‐3 (IL‐3) and granulocyte‐macrophage–colony stimulating factor (GM‐CSF) have synergistic, hematopoietic growth‐promoting activity in preclinical studies. Because of the paucity of effective therapies for patients with chronic bone marrow failure states, the authors studied the biologic activity of sequential IL‐3/GM‐CSF in such patients.
Defocus Incorporated Multiple Segments (DIMS) spectacle lenses slow myopia progression: a 2-year randomised clinical trial

Aim To determine if ‘Defocus Incorporated Multiple Segments’ (DIMS) spectacle lenses slow childhood myopia progression. Methods A 2-year double-masked randomised controlled trial was carried out in 183 Chinese children aged 8–13 years, with myopia between −1.00 and −5.00 D and astigmatism ≤1.50 D. Children were randomly assigned to wear DIMS (n=93) or single vision (SV) spectacle lenses (n=90). DIMS lens incorporated multiple segments with myopic defocus of +3.50 D. Refractive error (cycloplegic autorefraction) and axial length were measured at 6month intervals. Results 160 children completed the study, n=79 in the DIMS group and n=81 in the SV group. Average (SE) myopic progressions over 2 years were −0.41±0.06 D in the DIMS group and −0.85±0.08 D in the SV group. Mean (SE) axial elongation was 0.21±0.02 mm and 0.55±0.02 mm in the DIMS and SV groups, respectively. Myopia progressed 52% more slowly for children in the DIMS group compared with those in the SV group (mean difference −0.44±0.09 D, 95% CI −0.73 to −0.37, p<0.0001). Likewise, children in the DIMS group had less axial elongation by 62% than those in the SV group (mean difference 0.34±0.04 mm, 95% CI 0.22 to 0.37, p<0.0001). 21.5% children who wore DIMS lenses had no myopia progression over 2 years, but only 7.4% for those who wore SV lenses. Conclusions Daily wear of the DIMS lens significantly retarded myopia progression and axial elongation in myopic children. Our results demonstrated simultaneous clear vision with constant myopic defocus can slow myopia progression. Trial registration number NCT02206217.
Detection of human epidermal growth factor receptor 2 overexpression in canine anal sac gland carcinoma

Canine anal sac gland carcinoma (ASGC) frequently occurs in the apocrine glands of the canine anal sac and shows aggressive biological behavior. The expression of human epidermal growth factor receptor 2 (HER2) has been reported in various human and canine tumors. HER2 is a promising therapeutic target of these tumors, and HER2-targeted drugs, such as trastuzumab and lapatinib, have improved the outcome of these patients. In this study, HER2 expression in ASGC was evaluated to investigate its potential as a therapeutic target for canine ASGC. HER2 mRNA expression in surgically resected ASGC tissues was significantly higher than that in normal anal sac tissue. To evaluate the expression of HER2 protein, paraffin-embedded ASGC tissues were immunohistochemically evaluated. Strong and broad staining of HER2 was detected in ASGC tissues, while HER2 was weakly to moderately stained in normal anal sac apocrine glands and squamous epithelia. The degree of HER2 expression in ASGC tissues was scored based on its intensity and positivity (score: 0–3+). Scoring of HER2 expression revealed 6 samples (24%) scored 3+, 14 (56%) scored 2+, and 5 (20%) scored 1+, with no samples scoring 0. In all, 80% of canine ASGC tissues were positive for HER2 (scored ≥2+). Furthermore, putative HER2-overexpressed cells in ASGC were detected with trastuzumab by flow cytometry. These preliminary data may lead to further evaluation of the role of HER2 in canine ASGC as a mechanism of malignancy and as a therapeutic target for HER2-targeted therapy.
Negative correlation in neural systems

In our attempt to understand neural systems, it is useful to identify statistical principles that may be beneficial in neural information processing, outline how these principles may work in theory, and demonstrate the benefits through computational modelling and simulation. Negative correlation is one such principle, and is the subject of this work. The main body of the work falls into three parts. The first part demonstrates the space filling and accelerated central limit convergence benefits of negative correlation, both generally and in the specific neural context of V1 receptive fields. I outline two new algorithms combining traditional ICA with a correlation objective function. Correlated component analysis seeks components with a given correlation matrix, while correlated basis analysis seeks basis functions with a given correlation matrix. The benefits of recovering components and basis functions with negative correlations are shown. The second part looks at the functional role of negative correlation for integrate- and-fire neurons in the context of suprathreshold stochastic resonance, for neurons receiving Poisson inputs modelled by a diffusion approximation. I show how the SSR effect can be seen in networks of spiking neurons, and further show how correlation can be used to control the noise level, and that optimal information transmission occurs for negatively correlated inputs when parameters take biophysically plausible values. The final part examines the question of how negative correlation may be implemented in the context of small networks of spiking neurons. Networks of integrate-and-fire neurons with and without lateral inhibitory connections are tested, and the networks with the inhibitory connections are found to perform better and show negatively correlated firing patterns. This result is extended to more biophysically detailed neuron and synapse models, highlighting the robust nature of the mechanism. Finally, the mechanism is explained as a threshold-unit approximation to non-threshold maximum likelihood signal/noise decomposition.
Stem Cell Organoid Engineering

Organoid systems leverage the self-organizing properties of stem cells to create diverse multicellular tissue proxies. Most organoid models only represent single or partial components of a tissue, and it is often difficult to control the cell type, organization, and cell-cell/cell-matrix interactions within these systems. Herein, we discuss basic approaches to generate stem cell-based organoids, their advantages and limitations, and how bioengineering strategies can be used to steer the cell composition and their 3D organization within organoids to further enhance their utility in research and therapies.
Association of &bgr;-catenin with P-Smad3 but not LEF-1 dissociates in vitro profibrotic from anti-inflammatory effects of TGF-&bgr;1

Summary Transforming growth factor &bgr;1 (TGF-&bgr;1) is known to be both anti-inflammatory and profibrotic. Cross-talk between TGF-&bgr;/Smad and Wnt/&bgr;-catenin pathways in epithelial–mesenchymal transition (EMT) suggests a specific role for &bgr;-catenin in profibrotic effects of TGF-&bgr;1. However, no such mechanistic role has been demonstrated for &bgr;-catenin in the anti-inflammatory effects of TGF-&bgr;1. In the present study, we explored the role of &bgr;-catenin in the profibrotic and anti-inflammatory effects of TGF-&bgr;1 by using a cytosolic, but not membrane, &bgr;-catenin knockdown chimera (F-TrCP-Ecad) and the &bgr;-catenin/CBP inhibitor ICG-001. TGF-&bgr;1 induced nuclear Smad3/&bgr;-catenin complex, but not &bgr;-catenin/LEF-1 complex or TOP-flash activity, during EMT of C1.1 (renal tubular epithelial) cells. F-TrCP-Ecad selectively degraded TGF-&bgr;1-induced cytoplasmic &bgr;-catenin and blocked EMT of C1.1 cells. Both F-TrCP-Ecad and ICG-001 blocked TGF-&bgr;1-induced Smad3/&bgr;-catenin and Smad reporter activity in C1.1 cells, suggesting that TGF-&bgr;1-induced EMT depends on &bgr;-catenin binding to Smad3, but not LEF-1 downstream of Smad3, through canonical Wnt. In contrast, in J774 macrophages, the &bgr;-catenin level was low and was not changed by interferon-&ggr; (IFN-&ggr;) or lipopolysaccharide (LPS) with or without TGF-&bgr;1. TGF-&bgr;1 inhibition of LPS-induced TNF-&agr; and IFN-&ggr;-stimulated inducible NO synthase (iNOS) expression was not affected by F-TrCP-Ecad, ICG-001 or by overexpression of wild-type &bgr;-catenin in J774 cells. Inhibition of &bgr;-catenin by either F-TrCP-Ecad or ICG-001 abolished LiCl-induced TOP-flash, but not TGF-&bgr;1-induced Smad reporter, activity in J774 cells. These results demonstrate for the first time that &bgr;-catenin is required as a co-factor of Smad in TGF-&bgr;1-induced EMT of C1.1 epithelial cells, but not in TGF-&bgr;1 inhibition of macrophage activation. Targeting &bgr;-catenin may dissociate the TGF-&bgr;1 profibrotic and anti-inflammatory effects.
Effects of different exercise modalities on novel hepatic steatosis indices in overweight women with type 2 diabetes

Background/Aims Fatty liver is a clinical and pathologic condition in individuals with type 2 diabetes (T2D). The purpose of this study is to examine the effects of different exercise modalities on non-alcoholic fatty liver indices (fatty liver index [FLI], lipid accumulation product [LAP], hepatic steatosis index [HSI], and Framingham Steatosis Index [FSI]) in women with T2D. Methods Fifty-two women with T2D and a mean age of 55.07±5.92 yrs, body mass index (BMI) 28.94±4.09 kg/m2 , and hemoglobin A1c (HbA1c) 9.41±0.82% were randomized to a sprint interval training (SIT) (n=17), combined aerobic and resistance (A+R) training (n=17), or control group (n=18) for 10 weeks. Two-way repeated analysis of variance (ANOVA) was used to find differences between groups and the effects of time and Time×Group interactions after 10 weeks on non-alcoholic fatty liver indices. After this, ANOVA models were constructed to determine the effects of group allocation and change in non-alcoholic fatty liver indices. Results There were significant time interactions for FLI (P<0.001), HSI (P<0.001), and LAP (P<0.001). Also, there were significant Time×Group interactions for fasting blood glucose (P=0.034), and HbA1c (P=0.006). Conclusions Results highlight that exercise training, independent of mode of training, is an effective strategy to improve some indices related to hepatic steatosis and blood glucose profiles in women with T2D.
The influence of chlorination timing and concentration on microbial communities in labyrinth channels: implications for biofilm removal

Abstract Chlorination is an effective method to control biofilm formation in enclosed pipelines. To date, very little is known about how to control biofilms at the mesoscale in complex pipelines through chlorination. In this study, the dynamic of microbial communities was examined under different residual chlorine concentrations on the biofilms attached to labyrinth channels for drip irrigation using reclaimed water. The results indicated that the microbial phospholipid fatty acids, extracellular polymeric substances, microbial dynamics, and the ace and Shannon microbial diversity indices showed a gradual decrease after chlorination. However, chlorination increased microbial activity by 0.5–19.2%. The increase in the relative abundances of chloride-resistant bacteria (Acinetobacter and Thermomonas) could lead to a potential risk of chlorine resistance. Thus, keeping a low chlorine concentration (0.83 mg l−1 for 3 h) is effective for controlling biofilm formation in the labyrinth channels.
Inferring Micro-Activities Using Wearable Sensing for ADL Recognition of Home-Care Patients

In this study, we propose a novel, context-based, location-aware algorithm for identifying low-level micro-activities that can be used to derive complex activities of daily living (ADL) performed by home-care patients. This identification is achieved by gathering the location information of the target user by using a wearable beacon embedded with a magnetometer and inertial sensors. The shortcomings of beacon-signal stability and mismatch issues in magnetic-field sequences are overcome by adopting a hybrid, three-phase approach for deducing the locus of micro-activities and their associated zones in a smart home environment. The suggested approach is assessed in two different test environments, where the main intention is to map the location of a person performing an activity with pre-defined house landmarks and zones in the offline labeled database. In addition to the recognition of low-level activities, the proposed method also identifies the person's walking trajectory within the same zone or between different zones of the house. The experimental results demonstrate that it is possible to achieve centimeter-level accuracy for the recognition of micro-activities and to achieve the classification accuracy of 85% for trajectory prediction. These results are encouraging and imply that the collection of accurate low-level information for ADL recognition is possible using integration of inertial sensors, magnetic field and Bluetooth low energy (BLE) technologies from the wearable beacon without relying on other infrastructural sensors.
Continuous update of classification on a sequence of satellite images

This paper aims at monitoring agricultural areas using time series of satellite images, in order to obtain as early as possible in the year a classification of cultivated areas, as well as a characterisation of the different phenological behaviors for cultivated and natural land covers. For that purpose a learning phase has been performed, to provide a mathematical characterization of the land covers’ phenology in the test area during one or several reference years. The test phase, simulating the operational use of the system, consists in iteratively analysing satellite data acquired during the test year. Each time a new image is available, a classification is computed, that defines at the first level the land cover type, and at the second level the phenology. The accuracy of the classification improves when more images are available, providing a better information on phenology.
Activation of dendritic cells by crosslinked collagen hydrogels (artificial corneas) varies with their composition

Activated T cells are known to promote fibrosis, a major complication limiting the range of polymeric hydrogels as artificial corneal implants. As T cells are activated by dendritic cells (DC), minimally activating hydrogels would be optimal. In this study, we evaluated the ability of a series of engineered (manufactured/fabricated) and natural collagen matrices to either activate DC or conversely induce DC apoptosis in vitro. Bone marrow DC were cultured on a series of singly and doubly crosslinked hydrogels (made from recombinant human collagen III [RHCIII] or collagen mimetic peptide [CMP]) or on natural collagen‐containing matrices, MatrigelTM and de‐cellularised mouse corneal stroma. DC surface expression of major histocompatibility complex Class II and CD86 as well as apoptosis markers were examined. Natural matrices induced low levels of DC activation and maintained a “tolerogenic” phenotype. The same applied to singly crosslinked CMP‐PEG gels. RHCIII gels singly crosslinked using either N‐(3‐dimethylaminopropyl)‐N′‐ethylcarbodiimide with the coinitiator N‐hydroxy succinimide (EDC‐NHS) or N‐cyclohexyl‐N‐(2‐morpholinoethyl)carbodiimide metho‐p‐toulenesulfonate with NHS (CMC‐NHS) induced varying levels of DC activation. In contrast, however, RHCIII hydrogels incorporating an additional polymeric network of 2‐methacryloyloxyethyl phosphorylcholine did not activate DC but instead induced DC apoptosis, a phenomenon observed in natural matrices. This correlated with increased DC expression of leukocyte‐associated immunoglobulin‐like receptor‐1. Despite low immunogenic potential, viable tolerogenic DC migrated into and through both natural and manufactured RHCIII gels. These data show that the immunogenic potential of RHCIII gels varies with the nature and composition of the gel. Preclinical evaluation of hydrogel immunogenic/fibrogenic potential is recommended.
Effect of buffer conditions on CYP2C8-mediated paclitaxel 6α-hydroxylation and CYP3A4-mediated triazolam α- and 4-hydroxylation by human liver microsomes

Abstract 1. Buffer conditions in in vitro metabolism studies using human liver microsomes (HLM) have been reported to affect the metabolic activities of several cytochrome P450 (CYP) isozymes in different ways, although there are no reports about the dependence of CYP2C8 activity on buffer conditions. 2. The present study investigated the effect of buffer components (phosphate or Tris-HCl) and their concentration (10–200 mM) on the CYP2C8 and CYP3A4 activities of HLM, using paclitaxel and triazolam, respectively, as marker substrates. 3. The Km (or S50) and Vmax values for both paclitaxel 6α-hydroxylation and triazolam α- and 4-hydroxylation, estimated by fitting analyses based on the Michaelis–Menten or Hill equation, greatly depended on the buffer components and their concentration. 4. The CLint values in phosphate buffer were 1.2–3.0-fold (paclitaxel) or 3.1–6.4-fold (triazolam) higher than in Tris-HCl buffer at 50–100 mM. These values also depended on the buffer concentration, with a maximum 2.3-fold difference observed between 50 and 100 mM which are both commonly used in drug metabolism studies. 5. These findings suggest the necessity for optimization of the buffer conditions in the quantitative evaluation of metabolic clearances, such as in vitro–in vivo extrapolation and also estimating the contribution of a particular enzyme in drug metabolism.